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Mayor Don Wesely today gave an update on efforts to increase safety at two intersections. Since January 2000, the intersection of Warlick Boulevard and Old Cheney Road has been the site of 17 accidents, including one fatality. D uring the same time period, the intersection of 70th Street and Cornhusker Highway has been the site of 13 accidents, including one fatality.
"Although statistically, these two don't make the list of top ten accident intersections, serious accidents have occurred at these locations, and the public is concerned about them," said Mayor Wesely. "In addition to the steps we are taking, we need the public be more cautious when they approach these and all other intersections in our city."
Portable message signs which display the speed vehicles are moving were installed at both intersections November 20th.
Other work at 70th and Cornhusker includes:
Media Release


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Last Minute Halloween with Google
Posted: 1:18 PM, Oct 31, 2018
Updated: 2018-10-31 19:18:29Z
Copyright 2018 Scripps Media, Inc. All rights reserved. This material may not be published, broadcast, rewritten, or redistributed.
The Tucson Morning Blend
Southern Arizona's premiere local lifestyle show featuring Heather Rowe, focusing on providing you with informative, entertaining and useful content. This one-hour show airing weekdays at 11AM on KGUN9 and 1PM on The CW Tucson features local businesses, entertainers, chefs, health care providers, community leaders and important events in and around Tucson.

subset: commoncrawl


text:
Checkout Cart (7 Items)
07/28/2001 Goal Master [Miscellaneous]So you want to make concrete plans for your life, enter Goal Master! 6 databases allow you to track and prioritize all the important plans you have. Even if your getting on in years, you can still benefit from makeing a road map for life, after all how do you hit a target if your not aiming for it?! You should first enter your mission statement, this will help you to determine your goals in all aspects of your life. Enter your values and roles you have in life. Then set your goals and enter the tasks you have to do to complete those special tasks in life. Later evaluate your progress you have made. Have a good life and plan and do all the things you know you should.
07/21/2001 Money Watcher [Financial]Allows you to keep track of your checking, savings and cash accounts. You always know what you have! Make tranfers between accounts to.
07/29/2001 Christmas List [Miscellaneous]UPDATED!
Have you ever been talking to a friend or family member and their telling you what they want for Christmas? If your like me you always forget. An easy way to keep track of who wants what for Christmas. Check list for cards sent and the ones you got. *
07/22/2001 Santas Helper [Miscellaneous]Keep track of the People you need to buy for. You can keep track of what gifts you buy for everyone as well as Christmas cards sent. Even keeps a running total of how much you spent! Personal Info section to remember clothing sizes too. Hope you enjoy. HoHoHo. UPDATED: Bug in running total fixed.
07/28/2001 Class Time [Miscellaneous]3 Databases to make school easy! Class Time will allow you to enter in info for all the subjects you are taking. Put in your Schedule the location and what grade you got in it. The Professor database will keep info needed on your teacher, like what the teacher's office hours are, what his or her phone number is, E-Mail and things like that. The assignments database will keep track of the homework you get as well as exams that are up coming, the status of the work, it will even tell you how many days till your assignment is due!
11/03/2000 Special Events [Time Tracking]Simple Applet to allow you to track the number of days till that special event. Tells you how many days you have to procrastinate!
02/13/2001 Party Time [Fun]So your planning a party, but you need to know who to send invitations to, what suff to buy and a way to keep track of how much it all costs, so you don't blow the bank. Now you can. 4 databases to take care of all the things that need to get done. Easy way to plan and execute that special event.
11/23/2000 Vacation Time [Time Tracking]Have you ever wondered how much vacation time you have left?! Now you can keep track of it in a convenient easy to use interface, that allows you to put in the beginning and ending dates for your vacation. Takes into account number of hours in a work day and figures time used and displays remaining hours. Enter hours as you accumulate them and you will always know how much time you have to play!
11/28/2000 Movies [Entertainment]Ever wish you had a log of all your favorite movies? If your a movie freak like me you do. So now you can, uses 3 databases to let you keep track of the movies you've seen. Database for Stars of the show, another for Directors, and another for the movies. Now you have no excuse when somebody askes you about a movie you've seen, just whip out your Palm and start giving the facts.
09/07/2005 Money Watcher Silver [Financial]3 databases to take care of your financial needs, Will track Checking, Savings, and Cash accounts Plus will track credit cards.
02/13/2001 Pocket Journal [Time Tracking]Do you have to sit down and make a report to the boss at the end of the week? This is a useful applet for tracking your daily events, such as phone calls or meetings and what they where about. Also will time these events so you have a record of how long they took later. Now you can show the boss how productive you are! Hope you get a raise!


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Auto Repair Web Design In Oakton, VA
Looking to build or redesign your auto repair website? Look no further. We provide high quality auto repair web design for Oakton, VA! Do not settle for cookie cutter websites with bad logos and messy code. Our web design team understands appearances are important for both your auto customers and for your website's performance in Google search. Within a few seconds of opening a site, auto repair customers can decide whether or not they are interested in an auto company's services. For this reason, our web design team creates your auto repair website to be easy to navigate, unique, and responsive to the way the potential auto customer is viewing it. Your load time is monitored and website adjusted to have your website load faster, as search engines and auto customers show favor to auto repair websites that have a quick load time.
With Auto Shop Webmasters, you can always be sure your site is coded properly and well structured for search engines and auto customers alike. Let's get started on your auto company's new website and auto repair web design in Oakton today! Give us a call at 800.377.3068!
Interesting Market Data
Oakton, Virginia is home to 36,860 individuals. Out of the 32,400 locals who are on the web in Oakton, 16,524 (51%) are searching the internet from their smartphones. So what does this mean for your business? It means that having a website that loads quickly and is responsively designed will go a long way in reaching this audience!
Consider, too, that half of mobile searches are for nearby services, and over 60% of those inquiries resolve with a transaction of some sort. This is a big deal for local businesses! In light of this fact, your internet marketing must include mapping for the local area so that these consumers can find you as they search online.
85% (31,331 people in Oakton, VA) rely on web searches to locate products and service providers, and it's hard to ignore the impact of social media on the search process given that 16,956 (46%) consumers in Oakton, VA consider these platforms as they narrow down their options.
All of these facts point to the importance of having solid social media coverage and effective internet marketing in place! With nearly 32,400 (87.9%) people in Oakton, VA searching online, it's vital that your SEM strategy appeals to those potential customers and gets you noticed.
Organic SEO And Monthly Services
When creating your auto company's website, we do not just optimize the web design. We also enhance the content with auto repair organic SEO. Our content is brand new and created to adhere to Google's website guidelines. We use local keyword search terms and auto repair terms to aide in your performance with search engines when a person searches for automotive services in your area.
That is not all we do! On top of keeping your auto repair SEO at its best, we monitor your backlinks to ensure all remain valid. When an auto website has a good deal of bad backlinks within its text, Google will penalize it. We verify all links within your content and pages, keeping your auto company website in good standing with search engines.
Get Started!
Call us today at 800.377.3068! We provide complete auto repair SEO and auto repair web design for Oakton, VA auto shops! At Auto Shop Webmasters, we offer free consultations and do not require lengthy contracts to get started on your brand new auto repair website. Let our team get started on your website today!


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Quiet Giants should never be overlooked
SCOTTSDALE, Ariz. -- This is par for the course for the Giants. Five days removed from Opening Day in Arizona, they already are chasing the Dodgers.
No worries, mate. They're used to playing second fiddle in the National League West -- even when they're striking the best notes in the orchestra.
SCOTTSDALE, Ariz. -- This is par for the course for the Giants. Five days removed from Opening Day in Arizona, they already are chasing the Dodgers.
No worries, mate. They're used to playing second fiddle in the National League West -- even when they're striking the best notes in the orchestra.
In the standings as well as in the realm of the national media machinery, defending division champion Los Angeles is on top of the heap after taking two from Arizona in Sydney, Australia.
Off and running, Hollywood's team has the star power, the unmatched payroll and the widespread anticipation of a magical ending to the script this time around.
And their eternal rivals, the Giants? They have their privacy, their solitude and the undying love of their faithful fan base in the gorgeous city by the San Francisco Bay. Oh, they also have this: two World Series championships in the past four seasons, something no other team in the sport can flaunt.
"We don't feel like we've ever had the focus on us," Madison Bumgarner, the Giants' Opening Day starter, said. "We're a team not a lot of people [outside the Bay Area] talk about.
"Nobody gave us a chance to win in 2010 and 2012. Everyone thought we'd get beat in the division. We don't care if we don't get talked about. We just care about what we have to do to win."
The Dodgers roll out flamboyant, fascinating personalities, one after another. Yasiel Puig seems to get more national attention for his speed on the roadways and his unpredictable behavior than Giants catcher Buster Posey drew for winning the National League Most Valuable Player Award in 2012.
Like most of his teammates, Posey keeps his innermost thoughts to himself. The Giants take their cue from their leaders: Posey, Matt Cain and manager Bruce Bochy, the former catcher with the cool, relaxed style -- and impeccable professional profile.
"It doesn't matter to us at all," Bochy said when asked about the sizzle associated with the Dodgers. "From my standpoint, you understand the attention being focused on the Dodgers. The moves they've made, the players they've acquired, the things they've done on the field.
"We don't even talk about it. These guys are here to work and get ready to play baseball. That's it."
It was revealing how the Giants reacted in the aftermath of the Dodgers' blockbuster trade with the Red Sox on Aug. 25, 2012. Los Angeles acquired Adrian Gonzalez, Carl Crawford, Josh Beckett and Nick Punto for five players, the most prominent of whom was James Loney.
The expectation was that the expensive deal would lift the Dodgers, trailing the Giants by three games at the time, over San Francisco. The Giants were dealing with the 50-game ban of their hottest hitter, Melky Cabrera, for violating the MLB drug policy.
Taking seven of their final nine games against the Dodgers, the Giants pulled away and won the division by eight games. Bochy and Co. went on to stage one of the most remarkable runs in postseason history, coming from behind to subdue the Reds and Cardinals in the NL playoffs before sweeping the Tigers in the World Series.
How soon we forget.
A frustrating, disappointing 2013 season seemingly has taken the two-time champs off the national radar. Undone by a rash of injuries and substandard performances by leading lights, the Giants plunged to 76-86, 16 games off the Dodgers' pace.
They made two significant off-season moves, acquiring proven starter Tim Hudson and slugger Michael Morse. Essentially, they trusted their own, in-house talent.
Even-numbered seasons have brought out the best in this outfit. The inability to reach the postseason after their 2010 and '12 titles has produced a garden variety of theories in San Francisco.
"It's kind of odd how it's worked out," Bumgarner said. "But I'll take it every other year."
In spite of all their struggles, the Giants still managed to claim the series series, 11-8, from the Dodgers last year. Oddly, San Francisco, at 44-32, was seven games better than the Dodgers inside the division.
The NL Central (23-11) and American League (14-6) beat up on the defending champs, ruining their season.
None of this means a thing now to the unflappable Giants as they go about their business with a familiar resolve. Truth be known, they probably love the notion that they're once again sailing beneath the radar, not expected to make much of a splash off the Pacific Ocean.
Still waters do run deep.
"Our young guys -- Bumgarner, Posey, those guys -- are well-grounded, humble," Bochy said, unintentionally characterizing himself. "They appreciate what they have and what we've been able to accomplish here. They're determined to keep it going.
"We have our characters, too. Behind closed doors, we have some personalities here. It's a nice blend. It's always been a good mix here."
The team's most identifiable character from the 2010 championship cast -- "The Beard" -- happens to be a Dodger now. Wouldn't you know it? Post-surgery, closer Brian Wilson left, signing a free-agent deal with L.A. last season and regaining his prime-time stuff down the stretch.
Wilson is back for another run with manager Don Mattingly's colorful troupe this season, presumably as a $10 million setup man for Kenley Jansen.
That kind of thing never would happen in San Francisco, where the payroll is at least $60 million lower than that of the big spenders down south.
They might not be the most interesting men in the baseball world in the popular perception, but the Giants -- loaded with low-profile substance and armed with two championships -- should not be overlooked.
They have their bling, even if they don't flaunt it.
Lyle Spencer is a reporter for MLB.com.


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Woosa needed a new logo design and created a contest on 99designs.
A winner was selected from 133 designs submitted by 26 freelance designers.
Woosa Media
Woosa Media is a new social media marketing and management company. We will be providing support services to businesses to help them achieve their business goals by utilizing the power of social media, as an additional online advertising medium.
Services include managing social media accounts (such as Twitter, Facebook, LinkedIn, blogs etc.), building online audiences and followings, monitoring audience-created online mentions...
Effective social media management is about developing and maintaining positive, mutually beneficial relationships between business owners and their customers. It is about adding value, connecting and communicating with customers.
Our target audience is wide. We are targeting individuals, businesses and organizations in any industry (eg. local hairdresser or doctor, celebrities, speakers, restaurants, financial institutions...) and any size (eg. small local businesses, national businesses, or multinational companies...)
The logo is to be the company name, "Woosa Media". The two words are attractively balanced and it is a unique-sounding name – we would be excited to see creative submissions and potentially the emergence of a company mark/symbol from the full logo. Please include the slogan "Social Media Management" on the second level.
It should appear edgy and fresh but approachable. It should convey the company's core values: Proficiency, Innovation, Reliability, Friendliness.
No specific color requirement.
Intended Use
The company logo will be used in all branding - on the website, our own social media profiles, social media thumbnails, company intranet, company letterhead etc.
Find out how a design contest works or learn more about our logo design services.


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Here we go again. Seb and Max in the front row. Seb with a new clutch from COTA race so he should get a good start.
Autosport offers this race day article - https://www.autosport.com/f1/news/13...oughest-gp-yet
Formula 1 drivers are bracing themselves for the toughest mechanical challenge of the season in the Mexican Grand Prix, which is set to take a toll on engine and brake cooling.
Mexico's high altitude means the air is less dense and that makes it much harder for teams to keep the temperature of their cars under control.
Drivers have had to lift and coast at the end of straights to protect their brakes and engines from overheating in practice, and the situation will likely get worse in Sunday's race.
"It's a tough circuit for cooling, probably one of the most difficult of the year, because of the thin atmosphere and the huge amount of braking you've got to do without the benefit of drag," explained Williams technical chief Paddy Lowe.
"With the turbo engine, unlike a normally aspirated engine which is down on power, these engines are running normal power.
"So, you've got all the same heat, or in fact more, because the compressor is doing even more work.
"Then you get less cooling because there's less air mass through the radiators, but even more heat than normal, so it's a double whammy.


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It's been a whileAugust 5th, 2010 by cosmic_cat_1:hellokitty.com
Wow I haven't written in here in ages. :O
I have abandoned my wordpress blog now
But I have moved onto Tumblr!!!!
It's so much easier and the posts can be sent to twitter and facebook
I don't think I'll be writing in here anymore
But please check out my tumblr! A lot has happened since January!!!
It's sad when I finish a blog. Especially this one because I love Hello Kitty. But I must move onto easier ways of blogging. Sorry Sanrio.
Bye Bye


text: Part of the Napoleonic Wars (1803-15), the Battle of Trafalgar featured a clash of Franco-Spanish and British fleets off the western mouth of the Straits of Gibraltar. Commanded by Vice Admiral Nelson, the onslaught broke the allied line and exposed its center and rear to overwhelming force, resulting in the capture of 19 of the 33 Franco-Spanish ships. Although Lord Nelson was killed in the battle, he was largely credited for thwarting Napoleon's plans to concentrate a fleet in the Channel for the invasion of Britain.


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Corporal Robert Hollis, Machine Gun Corps
Postcard portrait by Pollard Graham, 108A Friargate, Derby, c.1917-1918
Image © and Courtesy of Fran Powles
Derby photographers were no exception, and it is informative to note that Pollard Graham shut eight of their branches in the Midlands - from Northampton to Burslem to Lincoln - between 1913 and 1916, leaving only the headquarters studio serving customers. Even after the war, it would be some time before business picked up sufficiently for the firms to contemplate expansion again, with their first post-war branch opening in 1920. Understandably, their clientele had changed too, with the majority of clients being uniformed soldiers about to head off to war. Postcards tended to be the predominantly used format. For most people there wasn't much spare cash around for the fancier mounts and frames.
Corporal Hollis of the Machine Gun Corps probably had this portrait taken on a visit home from the front, perhaps even after a period of recuperation, since he is sporting a wound stripe on his left sleeve.
The Brown family, Postcard portrait by Pollard Graham,
108A Friargate, Derby, 13 July 1917
Image © and Collection of Brett Payne
While most portraits tended to be a single figure, or perhaps couple, I am fortunate enough to have a group portrait of my grandmother's family, the Browns, taken in the summer of 1917. The older two of her three brothers are dressed in uniform. Arthur was a Corporal/Sergeant Dispenser, RAMC, and served with the 57th North Midlands Field Ambulance Unit. He became a chemist after the war. I'm not sure what unit Frank served in, and the insignia on his lapels are not clear enough for me to make out. Ethel worked as an apprentice milliner before the war, but during the war both she and her mother Edith served in some medical capacity, probably at a hospital in Derby. Edith has what appears to be an RAMC badge pinned to the front of her dress, Ethel some other type which I've been unable to identify. Percy was still at school, while Fred Brown, at 47, was presumably too old to be called for active service.
Unidentified Royal Navy man, perhaps with his father
Postcard portrait by Pollard Graham, 108A Friargate, Derby, c.1917-1918
Image © and Courtesy of Grace-Ellen Capier
This rather nice vignetted portrait shows an unidentified Royal Navy man seated with an older bearded gentleman who may be his father. I can't decide whether the single stripe on his left arm signifies that he holds the rank of "Able Seaman, Higher Grade," or whether it is a "Good Conduct" badge. Also just visible on his right sleeve is part of another badge. By comparison with Royal Navy Badges used during the First World War, it may be something like an Armourer's badge.
Thomas Frederick (Fred) Green, Royal Garrison Artillery
Postcard portrait by Pollard Graham, 108A Friargate, Derby, c.1917-1918
Image © and Courtesy of Betty Bowler
A very young Fred who also visited Pollard Graham's studio, probably on the eve of his departure for the front, is wearing standard Great War issue uniform with an RGA (Royal Garrison Artillery) shoulder title. The Medal Index Cards show a Thomas F. Green, 189835, Gunner in the Royal Garrison Artillery, entitled to the Victory and British War Medals.
Unidentified young man, Army Ordnance Corps, c.1914-1918
Postcard portrait by F.J. Boyes, 22 & 24 Osmaston Road, Derby
Image © and Collection of Brett Payne
Frederick J. Boyes was another Derby photographer who attended to portrait requirements of those dutiful young men during the Great War. The AOC shoulder title of this unidentified young man with his very neatly combed hair show that he served with the Army Ordnance Corps, which dealt "with the supply and maintenance of weaponry, munitions and other military equipment."
Uncle Bill (Notts & Derby Regiment) and Auntie Hilda, c.1914-1918
Postcard portrait by F.J. Boyes, 22 & 24 Osmaston Road, Derby
Image © and Collection of Brett Payne
This young man and his new bride (I presume from the prominently displayed wedding ring) are identified on the reverse only as Uncle Bill and Auntie Hilda, but he wears the shoulder titles of the Notts and Derbys Regiment, as well as a circular badge containing a red cross, similar to that of Arthur Brown, above, which may signify that he is some sort of medical orderly.
Charlotte and Alfred Horobin with their nieces, c.1915-1916
Postcard portrait by F.J. Boyes, 22 & 24 Osmaston Road, Derby
Image © and Courtesy of Sally Jackson
Sally Jackson sent me this portrait of her grandparents Alfred Irvin Horobin and his wife Charlotte Louisa née Brady with their nieces, daughters of his half brother, Arthur Swinfield Newton and his wife Lillia née Tomlinson. Alfred is dressed in uniform, wears shoulder titles of the RFA (Royal Field Artillery), and has a crown on his sleeve, suggesting he was a warrant officer. His finely waxed moustache, not clearly visible in this image, is certainly in keeping with that rank - all he needs is a swagger stick - but I've been unable to find an appropriate Medal Index Card for him.
Frederick William Lomas of Derby, c.1914-1916
Postcard portrait by R. & R. Bull, Ashbourne
Image © and Courtesy of Derek Smith
Unfortunately this portrait of a fresh-faced Frederick William Lomas, taken by the Ashbourne firm of R. & R. Bull early during the war, is not clear enough for me to read his shoulder titles.
Unidentified man and woman, c.1914-1918
Postcard portrait by H. Hinge, Ashbourne
Image © and Courtesy of Ellen Oakley
Henry Hinge, also of Ashbourne, took this rather wooden - and now pretty battered - portrait of a non-commissioned officer, identified on the reverse only as "Gran's brother," and his presumed wife. He has sergeant's stripes on his lower sleeve, as well as two wound stripes, and is also holding a swagger stick, which makes me wonder whether he is a drill or staff sergeant. His shoulder titles are not visible, and I'm not familiar enough with regimental badges to recognise the one on his cap.
Louisa and Doris McAuslan at Green Hall Hospital
Postcard portraits by Frederick Holbrook, George St Studios, Belper
Images © and Courtesy of Robert Silverwood
Louisa McAuslan and her daughter Doris were working for the Red Cross at Green Hall Hospital in Belper during the war, when Belper photographer Frederick Holbrook visited and took these two fine portraits.
Frank Tomlinson, c.1914-1918
Panel print portrait by Seaman & Sons, Chesterfield
Image © and Courtesy of Phil Gregory
This less common format by Seaman & Sons of Chesterfield is often known as a panel print, although it is not too different from a postcard cut into three, and I have often seen them constructed in that manner. Phil Gregory's relative Frank Tomlinson obviously served in a Scots Regiment during the war, as evidenced by his Glengarry hat, but I have no further information about him.
Sergeant George Manning, Royal Field Artillery, c.1917
Mounted print by W.W. Winter, Derby
Image © and Courtesy of Christine Hibbert
Sergeant George Manning of the Royal Field Artillery paid a visit to the studio of W.W. Winter in Midland Road Derby "whilst at home on leave from the battlefields of Europe." The single bar on his lower left sleeve is a wound stripe, indicating that he had already been wounded in the line of duty.
Geoff Caulton's PhotoDetective web pages have some excellent descriptions and images of uniforms, badges, shoulder titles and other tips for identifying subjects on portraits from the Great War.
Roger Capewell has an extensive web site devoted to Military Images, including a comprehensive list of badges with images.
For questions about the Great War, both of a specific and more general nature, the Great War Forum is well worth trying. Chris Baker's The Long, Long Trail gives valuable advice on how track a particular soldier's service during the war, including an excellent article on how to interpret Medal Index Cards.


text:
Report This
Category : Flow Chart.
Topic : Customer relationship management process flow chart. Author : Lorimar Bush.
Posted : Fri, Nov 16th 2018 08:10 AM.
Format : jpg/jpeg.
Well, flowcharts can be used to analyze, design, document or manage a process in a wide variety of fields. Examples could include a Recruitment or Accounting process, the logical procedure within a piece of software, or a process in an organization such as Health & Safety, Equal Opportunities, Conciliation & Arbitration or Social Services. There are several derivatives of the basic flowchart including the Workflow Diagram,


text:
Academic Appointments
Emeritus Faculty-Med Ctr Line, Surgery
A. Pediatric Immunosuppression with Current Emphasis on Development of Complete Steroid-Free Immunosuppression for Children
B. Changes in Hemodynamics and Blood Vessel Morphology Following Transplantation of Adult-Sized Kidneys to Infants and Small Children
C. Study of Immunological and Physiological Variances in Infants and Small Children following Renal Transplantation
D. Use of Small, Contracted Defunctionalized Urinary Bladders Following Kidney Transplantation
Rituximab will be tested for its safety and potential efficacy in treating B cell dense renal allograft rejection episodes in children receiving renal transplants at Stanford University
Stanford is currently not accepting patients for this trial. For more information, please contact MINNIE SARWAL, (650) 723 - 4517.
BACKGROUND: The copy number of donor-derived cell-free DNA (dd-cfDNA) in blood correlates with acute rejection (AR) in heart transplantation. We analyzed urinary dd-cfDNA as a surrogate marker of kidney transplant injury. METHODS: Sixty-three biopsy-matched urine samples (41 stable and 22 allograft injury) were analyzed from female recipients of male donors for chromosome Y (donor)-specific dd-cfDNA. All biopsies were semiquantitatively scored by a single pathologist. Standard statistical measures of correlation and significance were used. RESULTS: There was baseline scatter for urinary dd-cfDNA/μg urine creatinine across different patients, even at the time of stable graft (STA) function (undetected to 12.26 copies). The mean urinary dd-cfDNA in AR (20.5±13.9) was significantly greater compared with STA (2.4±3.3; P<0.0001) or those with chronic allograft injury (CAI; 2.4±2.4; P=0.001) but no different from BK virus nephropathy (BKVN; 20.3±15.7; P=0.98). In AR and BKVN, the intrapatient drift was highly significant versus STA or CAI patients (10.3±7.4 in AR; 12.3±8.4 in BKVN vs. -0.5±3.5 in STA and 2.3±2.6 in CAI; P<0.05). Urinary dd-cfDNA correlated with protein/creatinine ratio (r=0.48; P<0.014) and calculated glomerular filtration rate (r=-0.52; P<0.007) but was most sensitive for acute allograft injury (area under the curve=0.80; P<0.0006; 95% confidence interval, 0.67-0.93). CONCLUSION: Urinary dd-cfDNA after renal transplantation has patient specific thresholds, reflecting the apoptotic injury load of the donor organ. Serial monitoring of urinary dd-cfDNA can be a surrogate sensitive biomarker of acute injury in the donor organ but lacks the specificity to distinguish between AR and BKVN injury.
View details for DOI 10.1097/TP.0b013e318295ee5a
View details for PubMedID 23756769
The development of anti-donor humoral responses after transplantation associates with higher risks for acute rejection and 1-year graft survival in adults, but the influence of humoral immunity on transplant outcomes in children is not well understood. Here, we studied the evolution of humoral immunity in low-risk pediatric patients during the first 2 years after renal transplantation. Using data from 130 pediatric renal transplant patients randomized to steroid-free (SF) or steroid-based (SB) immunosuppression in the NIH-SNSO1 trial, we correlated the presence of serum anti-HLA antibodies to donor HLA antigens (donor-specific antibodies) and serum MHC class 1-related chain A (MICA) antibody with both clinical outcomes and histology identified on protocol biopsies at 0, 6, 12, and 24 months. We detected de novo antibodies after transplant in 24% (23% of SF group and 25% of SB group), most often after the first year. Overall, 22% developed anti-HLA antibodies, of which 6% were donor-specific antibodies, and 6% developed anti-MICA antibody. Presence of these antibodies de novo associated with significantly higher risks for acute rejection (P=0.02), chronic graft injury (P=0.02), and decline in graft function (P=0.02). In summary, antibodies to HLA and MICA antigens appear in approximately 25% of unsensitized pediatric patients, placing them at greater risk for acute and chronic rejection with accelerated loss of graft function. Avoiding steroids does not seem to modify this incidence. Whether serial assessments of these antibodies after transplant could guide individual tailoring of immunosuppression requires additional study.
View details for DOI 10.1681/ASN.2012070663
View details for Web of Science ID 000316921700017
View details for PubMedID 23449533
View details for PubMedCentralID PMC3609135
Monitoring of renal graft status through peripheral blood (PB) rather than invasive biopsy is important as it will lessen the risk of infection and other stresses, while reducing the costs of rejection diagnosis. Blood gene biomarker panels were discovered by microarrays at a single center and subsequently validated and cross-validated by QPCR in the NIH SNSO1 randomized study from 12 US pediatric transplant programs. A total of 367 unique human PB samples, each paired with a graft biopsy for centralized, blinded phenotype classification, were analyzed (115 acute rejection (AR), 180 stable and 72 other causes of graft injury). Of the differentially expressed genes by microarray, Q-PCR analysis of a five gene-set (DUSP1, PBEF1, PSEN1, MAPK9 and NKTR) classified AR with high accuracy. A logistic regression model was built on independent training-set (n = 47) and validated on independent test-set (n = 198)samples, discriminating AR from STA with 91% sensitivity and 94% specificity and AR from all other non-AR phenotypes with 91% sensitivity and 90% specificity. The 5-gene set can diagnose AR potentially avoiding the need for invasive renal biopsy. These data support the conduct of a prospective study to validate the clinical predictive utility of this diagnostic tool.
View details for DOI 10.1111/j.1600-6143.2012.04253.x
View details for Web of Science ID 000309180000018
View details for PubMedID 23009139
To determine whether steroid avoidance in pediatric kidney transplantation is safe and efficacious, a randomized, multicenter trial was performed in 12 pediatric kidney transplant centers. One hundred thirty children receiving primary kidney transplants were randomized to steroid-free (SF) or steroid-based (SB) immunosuppression, with concomitant tacrolimus, mycophenolate and standard dose daclizumab (SB group) or extended dose daclizumab (SF group). Follow-up was 3 years posttransplant. Standardized height Z-score change after 3 years follow-up was -0.99 ± 2.20 in SF versus -0.93 ± 1.11 in SB; p = 0.825. In subgroup analysis, recipients under 5 years of age showed improved linear growth with SF compared to SB treatment (change in standardized height Z-score at 3 years -0.43 ± 1.15 vs. -1.07 ± 1.14; p = 0.019). There were no differences in the rates of biopsy-proven acute rejection at 3 years after transplantation (16.7% in SF vs. 17.1% in SB; p = 0.94). Patient survival was 100% in both arms; graft survival was 95% in the SF and 90% in the SB arms (p = 0.30) at 3 years follow-up. Over the 3 year follow-up period, the SF group showed lower systolic BP (p = 0.017) and lower cholesterol levels (p = 0.034). In conclusion, complete steroid avoidance is safe and effective in unsensitized children receiving primary kidney transplants.
View details for DOI 10.1111/j.1600-6143.2012.04145.x
View details for Web of Science ID 000309180000019
View details for PubMedID 22694755
View details for PubMedCentralID PMC3681527
Steroid avoidance is safe and effective in children receiving kidney transplants in terms of graft function and survival, but the effects on allograft histology are unknown. In this multicenter trial, 130 pediatric renal transplant recipients were randomized to steroid-free (SF; n = 60) or steroid-based (SB; n = 70) immunosuppression, and underwent renal allograft biopsies at the time of graft dysfunction and per protocol at implantation and 6, 12 and 24 months after transplantation. Clinical follow-up was 3 years posttransplant. Subclinical acute rejection was present in 10.6% SF versus 11.3% SB biopsies at 6 months (p = 0.91), 0% SF versus 4.3% SB biopsies at 1 year (p = 0.21) and 0% versus 4.8% at 2 years (p = 0.20). Clinical acute rejection was present in 13.3% SF and 11.4% SB patients by 1 year (p = 0.74) and in 16.7% SF and 17.1% SB patients by 3 years (p = 0.94) after transplantation. The cumulative incidence of antibody-mediated rejection was 6.7% in SF and 2.9% in SB by 3 years after transplantation (p = 0.30). There was a significant increase in chronic histological damage over time (p < 0.001), without difference between SF and SB patients. Smaller recipient size and higher donor age were the main risk factors for chronic histological injury in posttransplant biopsies.
View details for DOI 10.1111/j.1600-6143.2012.04144.x
View details for Web of Science ID 000309180000020
View details for PubMedID 22694733
The degree of progressive chronic histological damage is associated with long-term renal allograft survival. In order to identify promising molecular targets for timely intervention, we examined renal allograft protocol and indication biopsies from 120 low-risk pediatric and adolescent recipients by whole-genome microarray expression profiling. In data-driven analysis, we found a highly regulated pattern of adaptive and innate immune gene expression that correlated with established or ongoing histological chronic injury, and also with development of future chronic histological damage, even in histologically pristine kidneys. Hence, histologically unrecognized immunological injury at a molecular level sets the stage for the development of chronic tissue injury, while the same molecular response is accentuated during established and worsening chronic allograft damage. Irrespective of the hypothesized immune or nonimmune trigger for chronic allograft injury, a highly orchestrated regulation of innate and adaptive immune responses was found in the graft at the molecular level. This occurred months before histologic lesions appear, and quantitatively below the diagnostic threshold of classic T-cell or antibody-mediated rejection. Thus, measurement of specific immune gene expression in protocol biopsies may be warranted to predict the development of subsequent chronic injury in histologically quiescent grafts and as a means to titrate immunosuppressive therapy.
View details for DOI 10.1038/ki.2011.245
View details for Web of Science ID 000297541900014
View details for PubMedID 21881554
Children with small capacity, defunctionalized urinary bladders present unique operative challenges. Thus, traditional practice has included pretransplant bladder augmentation, but this has several adverse consequences.A single-institutional, retrospective review from January 1, 2004 to December 31, 2008 was conducted. Twelve pediatric patients, whom had not undergone pretransplant bladder augmentation, did not have neurogenic bladders or require preoperative catheterization, and a small capacity defunctionalized bladders were included. All were managed by the same surgeon with a previously described ureteral implantation, and a 7F ureteral stent attached to a large diameter suprapubic catheter was removed in a joint manner without cystoscopy at 2 weeks. Data were collected on patient and graft survival, rejection episodes, urinary tract infection (UTI) requiring antibiotics, grade of vesicoureteral reflux, and posttransplant bladder capacity.One-year patient and graft survival rates were 100%. One patient experienced a clinical rejection episode, which was successfully treated. Five patients (41.7%) had a UTI requiring abx treatment within the first postoperative year, but at 1 year, all patients had sterile urinary tracts. After removal of suprapubic catheters and ureteral stents, all patients were able to void spontaneously. Seven patients had no posttransplant ureteral reflux, three had grade 1 reflux, and two had grade 3 reflux (both successfully treated). The average age estimated pretransplant bladder and 1 year posttransplant bladder capacity was 14.5% and 84% of expected, respectively.In pediatric end-stage renal disease patients with a small capacity defunctionalized bladder, it is reasonable to proceed with kidney transplantation without pretransplant bladder augmentation, thus avoiding an unnecessary surgery.
View details for DOI 10.1097/TP.0b013e318204381a
View details for Web of Science ID 000287127600015
View details for PubMedID 21283065
Given the recent withdrawal of daclizumab (DAC), the safety and efficacy of thymoglobulin (TMG) was tested as an alternative induction agent for steroid-free (SF) immunosuppression in pediatric kidney transplant recipients.Thirteen pediatric renal transplant recipients meeting defined high-risk criteria at transplantation were offered TMG induction and SF immunosuppression with maintenance mycophenolate mofetil and tacrolimus between October 2008 and January 2010. Patients were closely monitored at baseline, 3, 6, 9, and 12 months posttransplant for protocol biopsy and clinical outcomes. Outcomes were compared with 13 consecutively transplanted low-risk patients receiving an established DAC-based SF protocol (Sarwal et al., WA, American Transplant Congress 2003).There was a significant trend for overall decrease in the absolute lymphocyte counts in TMG group (F=5.86, mixed model group effect P=0.02), predominately at 3 months compared with DAC group (0.7±0.6 vs. 2.1±1.0, P=0.0004); however, lymphocyte count was recovered and was back to reference range by 6 months in TMG. There was trend toward more subclinical cytomegalovirus (15% vs. 0%) and BK viremia (17% vs. 0%) in the TMG group, with no differences in the incidence of subclinical Epstein Barr virus viremia (23% vs. 31%) or clinical viral disease. Mean graft function was excellent, and with a minimum follow-up of 6 months, there were no episodes of acute rejection.TMG seems to be a safe alternative induction strategy in patients for SF immunosuppression in pediatric renal transplantation. Extended follow-up and greater enrollment are necessary to fully explore the impact of TMG dosing on viral replication posttransplantation.
View details for DOI 10.1097/TP.0b013e3181fc8937
View details for Web of Science ID 000285377100042
View details for PubMedID 20935596
Small pediatric recipients of an adult-sized kidney have insufficient renal blood flow early after transplantation, with secondary chronic hypoperfusion and irreversible histological damage of the tubulo-interstitial compartment. It is unknown whether this is reflected by renal resistive indices. We measured renal graft resistive indices and volumes of 47 healthy pediatric kidney transplant recipients of an adult-sized kidney in a prospective study for six months post-transplant. A total of 205 measurements were performed. The smallest recipients (BSA
View details for DOI 10.1111/j.1399-3046.2009.01180.x
View details for Web of Science ID 000273478100024
View details for PubMedID 19413712
Acute rejection episodes are almost inevitable in the face of immunosuppression non-adherence and a known risk factor for developing chronic allograft nephropathy and accelerated graft loss. Daclizumab, a humanized monoclonal antibody directed against the alpha chain of the IL-2 receptor, is an important advance for induction therapy in renal transplant immunosuppression, reducing early acute graft rejection without affecting the tolerability of standard immunosuppression, for both steroid-based and steroid-free immunosuppressive protocols, in children and adults. In the absence of depot immunosuppression for maintenance therapy, we explored extended daclizumab therapy as temporary maintenance immunosuppression for acute rejection prophylaxis in two patients with recalcitrant immunosuppression non-adherence. Both patients had prior episodes of aggressive acute rejection associated with their non-adherence but achieved stable and rejection-free renal allograft function with daclizumab monotherapy in the presence of documented non-adherence thus providing an effective bridge for up to 12 months until immunosuppression adherence was re-established with ongoing psychosocial support. This report suggests that daclizumab monotherapy over an extended period of time during the period of non-adherence in the post transplant period could be a rescue modality to avoid immune activation and thereby prevent acute rejection in the face of erratic maintenance immunosuppression.
View details for DOI 10.1111/j.1399-3046.2008.01081.x
View details for Web of Science ID 000270666600024
View details for PubMedID 19017291
A disparity remains between graft survival of renal allografts from deceased donors and from living donors. A better understanding of the molecular mechanisms that underlie this disparity may allow the development of targeted therapies to enhance graft survival. Here, we used microarrays to examine whole genome expression profiles using tissue from 53 human renal allograft protocol biopsies obtained both at implantation and after transplantation. The gene expression profiles of living-donor kidneys and pristine deceased-donor kidneys (normal histology, young age) were significantly different before reperfusion at implantation. Deceased-donor kidneys exhibited a significant increase in renal expression of complement genes; posttransplantation biopsies from well-functioning, nonrejecting kidneys, regardless of donor source, also demonstrated a significant increase in complement expression. Peritransplantation phenomena, such as donor death and possibly cold ischemia time, contributed to differences in complement pathway gene expression. In addition, complement gene expression at the time of implantation was associated with both early and late graft function. These data suggest that complement-modulating therapy may improve graft outcomes in renal transplantation.
View details for DOI 10.1681/ASN.2008111145
View details for Web of Science ID 000268903200028
View details for PubMedID 19443638
View details for PubMedCentralID PMC2723986
Short-term outcomes using steroid-free immunosuppression after renal transplantation have been promising. No studies have examined the incidence of and reasons for steroid-avoidance protocol failures.We present a single-center analysis of steroid-free immunosuppression failures among 129 pediatric renal transplant recipients with mean follow-up of 5 years. We analyzed causes for failure and examined reasons for conversion to steroid-based therapy. We compared actual patient and allograft survival and allograft function in the cohort of patients who required conversion to steroid-based immunosuppression with that of the cohort maintaining steroid-free immunosuppression.A total of 13.2% (17/129) of patients failed steroid-free immunosuppression. Actual patient survival was equivalent in the two cohorts, 96.4% for the cohort maintaining steroid-free immunosuppression and 94.1% for those requiring conversion. Actual allograft survival was lower in patients requiring conversion to a steroid-based protocol, 76.5% vs. 95.5% (P=0.004). Estimated glomerular filtration rates 12-months and 24-months posttransplant were greater in patients maintaining steroid-free immunosuppression (P=0.003). Most patients (52.9%, 9/17) who broke the steroid-free protocol did so because of refractory acute rejection. The second most common reason was recurrence of glomerulonephritis (GN; 35.3%, 6/17).The failure rate of steroid-free immunosuppression among selective pediatric patients undergoing renal transplantation is low. Patients maintaining steroid-free immunosuppression have better allograft survival and function than those requiring conversion to steroid-based therapy. The most common reasons for failure of steroid-free immunosuppression are recalcitrant or recurrent allograft rejection and recurrent GN; the role of conversion to steroid-based immunosuppression after episodes of acute rejection and recurrent GN requires additional analysis.
View details for DOI 10.1097/TP.0b013e3181a5df60
View details for Web of Science ID 000266889900022
View details for PubMedID 19502970
View details for PubMedCentralID PMC2758080
Despite early promising patient and graft outcomes with steroid-free (SF) immunosuppression in pediatric kidney transplant recipients, data on long-term safety and efficacy results are lacking. We present our single-center experience with 129 consecutive pediatric kidney transplant recipients on SF immunosuppression, with a mean follow-up of 5 years. Outcomes are compared against a matched cohort of 57 concurrent recipients treated with steroid-based (SB) immunosuppression. In the SF group, 87% of kidney recipients with functioning grafts remain corticosteroid-free. Actual intent-to-treat SF (ITT-SF) and still-on-protocol SF patient survivals are 96% and 96%, respectively, actual graft survivals for both groups are 93% and 96%, respectively and actual death-censored graft survivals for both groups are 97% and 99%, respectively. Unprecedented catch-up growth is observed in SF recipients below 12 years of age. Continued low rates of acute rejection, posttransplant diabetes mellitus (PTDM), hypertension and hyperlipidemia are seen in SF patients, with sustained benefits for graft function. In conclusion, extended enrollment and longer experience with SF immunosuppression for renal transplantation in low-risk children confirms protocol safety, continued benefits for growth and graft function, low acute rejection rates and reduced cardiovascular morbidity.
View details for DOI 10.1111/j.1600-6143.2009.02640.x
View details for Web of Science ID 000266448900017
View details for PubMedID 19459814
View details for PubMedCentralID PMC2724986
View details for DOI 10.1111/j.1399-3046.2008.01064.x
View details for Web of Science ID 000264891700002
View details for PubMedID 19067918
We report 1-year outcomes of a randomized study of Rituximab versus standard-of-care immunosuppression (Thymoglobulin and/or pulse steroids) for treatment of biopsy confirmed, acute transplant rejection with B-cell infiltrates, in 20 consecutive recipients (2-23 years). Graft biopsies, with Banff and CADI scores, CD20 and C4d stains, were performed at rejection and 1 and 6 months later. Peripheral blood CMV, EBV and BK viral loads, graft function, DSA, immunoglobulins, serum humanized antichimeric antibody (HACA) and Rituximab, and lymphocyte counts were monitored until 1 year posttreatment. Rituximab infusions were given with a high index of safety without HACA development and increased infections complications. Rituximab therapy resulted in complete tissue B-cell depletion and rapid peripheral B-cell depletion. Peripheral CD19 cells recovered at a mean time of approximately 12 months. There were some benefits for the recovery of graft function (p = 0.026) and improvement of biopsy rejection scores at both the 1- (p = 0.0003) and 6-month (p < 0.0001) follow-up biopsies. Reappearance of C4d deposition was not seen on follow-up biopsies after Rituximab therapy, but was seen in 30% of control patients. There was no change in DSA in either group, independent of rejection resolution. This study reports safety and suggests further investigation of Rituximab as an adjunctive treatment for B-cell-mediated graft rejection.
View details for DOI 10.1111/j.1600-6143.2008.02411.x
View details for Web of Science ID 000261053600021
View details for PubMedID 18808404
Children with end-stage renal disease and inferior vena cava (IVC) thrombosis are rare, and their condition is complex and high risk for renal transplantation. Detailed imaging studies of the recipient's abdominal vasculature should be carried out prior to transplantation, followed by careful pre-operative joint planning by the pediatric transplant surgeon and nephrologist. Critical decisions need to be made as to whether a deceased child's kidney or an adult-sized kidney is to be used, and if the latter, whether it should be from a deceased or living donor. In addition, the contemplated site of the donor's renal vein anastomosis needs to be determined with a consideration of the possible consequences of the various choices. Sixteen cases of renal transplantation in children with pre-existing IVC thrombosis are reviewed, including the three reported by Shenoy et al. in this journal. With a full understanding of the difficulties noted, renal transplantation in a small child with IVC thrombosis can be successful. However, it requires thorough recipient assessment, coupled with a careful and thoughtful examination of options, to determine the best possible approach to the transplantation.
View details for DOI 10.1007/s00467-008-0951-6
View details for Web of Science ID 000260542400001
View details for PubMedID 18688652
With the increasing adoption of steroid-sparing immunosuppression protocols in renal transplantation, it is important to evaluate any adverse effects of steroid avoidance on graft function. Early graft function, measured by CrCl was retrospectively studied in 158 consecutive pediatric renal transplant recipients from 1996 to 2005, receiving either steroid-free or steroid-based immunosuppression. Patients receiving steroid-free immunosuppression vs. steroid-based immunosuppression had no difference change in CrCl (DeltaCrCl) in the first week post-transplantation (p = 0.12). When stratified by corticosteroid usage, patients with higher tacrolimus trough levels (> or =14 ng/mL) had slower graft function recovery in the first week post-transplantation than those with lower tacrolimus trough levels (p = 0.008) in the steroid-free group only. Despite initial slower graft function recovery in this subgroup, there was no negative impact on graft function in the steroid-free group; in fact steroid-free patients trended towards better CrCl at six months (p = 0.047) and 12 months (p < 0.001) post-transplant than the steroid-based group. With the improved immunological outcomes with steroid avoidance, close surveillance should be performed of tacrolimus levels to avoid levels >14 ng/mL. In patients with slow recovery of early graft function, short-term perioperative steroids may be considered.
View details for DOI 10.1111/j.1399-3046.2007.00884.x
View details for Web of Science ID 000258287900017
View details for PubMedID 18179640
Intra-graft CD20(+) B-cell clusters are found during acute rejection of renal allografts and correlate with graft recovery following rejection injury. Here using archived kidney tissue we conducted immunohistochemical studies to measure specific subsets of pathogenic B cells during graft rejection. Cluster-forming CD20(+) B cells in the rejected graft are likely derived from the recipient and are composed of mature B cells. These cells are activated (CD79a(+)), and present MHC Class II antigen (HLADR(+)) to CD4(+) T cells. Some of these clusters contained memory B cells (CD27(+)) and they did not correlate with intra-graft C4d deposition or with detection of donor-specific antibody. Further, several non-cluster forming CD20(-) B-lineage CD38(+) plasmablasts and plasma cells were found to infiltrate the rejected grafts and these cells strongly correlated with circulating donor-specific antibody, and to a lesser extent with intra-graft C4d. Both CD20(+) B cells and CD38(+) cells correlated with poor response of the rejection to steroids. Reduced graft survival was associated with the presence of CD20 cells in the graft. In conclusion, a specific subset of early lineage B cells appears to be an antigen-presenting cell and which when present in the rejected graft may support a steroid-resistant T-cell-mediated cellular rejection. Late lineage interstitial plasmablasts and plasma cells may also support humoral rejection. These studies suggest that detailed analysis of interstitial cellular infiltrates may allow better use of B-cell lineage specific treatments to improve graft outcomes.
View details for DOI 10.1038/ki.2008.249
View details for Web of Science ID 000258531800019
View details for PubMedID 18547992
CNI withdrawal may be employed as a "rescue" strategy for patients with established renal allograft injury and/or declining allograft function, with the aim at eliminating CNI-associated nephrotoxic effects. This analysis reviews outcomes in a pediatric population and identifies risk factors for adverse events post-CNI withdrawal. We performed a retrospective analysis of 17 pediatric renal transplants who underwent CNI withdrawal, with conversion to sirolimus and MMF. Mean CrCl decreased from 64.3 +/- 22 to 59.38 +/- 28.6 mL/min/1.73 m(2) (p = 0.04) at six months and 57.46 +/- 31.1 mL/min/1.73 m(2) (p = 0.02) at 12 months post-withdrawal. Forty-one percent of patients experienced AR. Increased risk for AR was associated with prior AR history, lower sirolimus trough levels, and lower CNIT biopsy scores. Graft loss (24%) was associated with worse CrCl, proteinuria, and histologic chronicity. Proteinuria (spot protein/creatinine ratio) increased from 0.75 +/- 1.0 to 1.71 +/- 2.0 (p = 0.03), unrelated to de novo sirolimus use. Four patients returned to CNI-based immunosuppression due to AR (n = 3) and gastrointestinal side effects (n = 1). Careful selection of pediatric candidates for CNI withdrawal is recommended. Worsening graft function and graft loss may be minimized by selecting patients with high CNIT scores and low biopsy chronicity and excluding patients with prior AR history.
View details for DOI 10.1111/j.1399-3046.2007.00847.x
View details for Web of Science ID 000257700900013
View details for PubMedID 18564305
In contrast to adult kidney recipients, in whom the long-term evolution and clinical determinants of tacrolimus pharmacokinetics are well studied, less is known about the long-term evolution of tacrolimus pharmacokinetics in pediatric kidney transplant recipients.One-hundred and five pediatric recipients of a kidney allograft, all treated with a corticosteroid-free immunosuppressive protocol, were included. The evolution of tacrolimus doses and predose trough (C0) levels was recorded at 3, 6, 9, 12, 18, and 24 months after transplantation, as well as all C0 levels obtained in the first 2 years after transplantation. The evolution and clinical determinants of tacrolimus exposure parameters were analyzed.Dose-corrected tacrolimus C0 levels (C0/dose/kg) increased in the first 2 years after kidney transplantation in pediatric recipients (P=0.001). This decrease in dose requirement by time was only significant in children older than 5 years at the time of transplantation (P=0.38, 0.03, and 0.001 for age groups <5, 5-12, and >12 years, respectively). In addition, the younger patients had significantly higher dose requirements (dose/kg) compared with older recipients (P=0.0002).Pediatric kidney transplant recipients exhibit maturation of dose-corrected tacrolimus predose trough levels with time after transplantation. This cannot be explained by differences in corticosteroid use, because all patients were treated with a corticosteroid-free protocol. The higher dose requirements for younger recipients and the absence of tacrolimus maturation in the youngest recipients suggest that age-dependent changes in tacrolimus intestinal first-pass effect, metabolism, or distribution play a role. Whether age-specific tacrolimus dosing algorithms will improve outcome needs further study.
View details for DOI 10.1097/TP.001361816431a
View details for Web of Science ID 000255318200014
View details for PubMedID 18431234
To describe the evolution, risk factors and impact of nonimmune histological injury after pediatric kidney transplantation, we analyzed 245 renal allograft protocol biopsies taken regularly from the time of transplantation to 2 years thereafter in 81 consecutive rejection-free pediatric recipients of an adult-sized kidney. Isometric tubular vacuolization was present early after transplantation was not progressive, and was associated with higher tacrolimus pre-dose trough levels. Chronic tubulo-interstitial damage and tubular microcalcifications were already noted at 3 months, were progressive and had a greater association with small recipient size, male donor gender, higher donor age and female recipient gender, but not with tacrolimus exposure. Renal function assessment showed that older recipients had a significant increase in absolute glomerular filtration rate with time after transplantation, which differed from small recipients who showed no increase. It is concluded that progressive, functionally relevant, nonimmune injury is detected early after adult-sized kidney transplantation in pediatric recipients. Renal graft ischemia associated with the donor-recipient size discrepancy appears to be a greater risk factor for this chronic histological injury, suggesting that the exploration of additional therapeutic approaches to increase allograft perfusion could further extend the graft survival benefit of adult-sized kidneys transplanted into small children.
View details for DOI 10.1111/j.1600-6143.2007.01949.x
View details for Web of Science ID 000250077600010
View details for PubMedID 17725681
Long-term allograft survival generally requires lifelong immunosuppression (IS). Rarely, recipients display spontaneous "operational tolerance" with stable graft function in the absence of IS. The lack of biological markers of this phenomenon precludes identification of potentially tolerant patients in which IS could be tapered and hinders the development of new tolerance-inducing strategies. The objective of this study was to identify minimally invasive blood biomarkers for operational tolerance and use these biomarkers to determine the frequency of this state in immunosuppressed patients with stable graft function. Blood gene expression profiles from 75 renal-transplant patient cohorts (operational tolerance/acute and chronic rejection/stable graft function on IS) and 16 healthy individuals were analyzed. A subset of samples was used for microarray analysis where three-class comparison of the different groups of patients identified a "tolerant footprint" of 49 genes. These biomarkers were applied for prediction of operational tolerance by microarray and real-time PCR in independent test groups. Thirty-three of 49 genes correctly segregated tolerance and chronic rejection phenotypes with 99% and 86% specificity. The signature is shared with 1 of 12 and 5 of 10 stable patients on triple IS and low-dose steroid monotherapy, respectively. The gene signature suggests a pattern of reduced costimulatory signaling, immune quiescence, apoptosis, and memory T cell responses. This study identifies in the blood of kidney recipients a set of genes associated with operational tolerance that may have utility as a minimally invasive monitoring tool for guiding IS titration. Further validation of this tool for safe IS minimization in prospective clinical trials is warranted.
View details for DOI 10.1073/pnas.0705834104
View details for Web of Science ID 000249806900050
View details for PubMedID 17873064
View details for PubMedCentralID PMC2000539
This report describes an unusual presentation of severe hypertension (HTN) in a subset of pediatric kidney recipients treated with a steroid avoidance pediatric renal transplantation protocol. The HTN was secondary to atypical, reno-vascular abnormalities (RVA) of the transplanted vasculature, temporally associated with erythropoietin (EPO) use.To investigate the clinical significance underlying this event, a retrospective clinical study of 100 pediatric renal transplants was undertaken (50 steroid-free and 50 matched steroid-based controls), with peripheral blood transcriptional analysis of four RVA patients and controls.Regardless of a higher observed incidence of anemia (p < 0.001) and greater overall EPO usage in the first post-transplant year in steroid-free patients, the incidence of new-onset HTN at one yr was significantly less in the steroid-free cohort (p = 0.03). Nevertheless, early EPO (first week post-transplant) was significantly associated with the combinatory findings of new-onset HTN (p = 0.03) and RVA (p = 0.007). Molecular mechanisms of RVA injury were investigated further by peripheral blood cDNA microarray gene expression profiling. A panel of 42 transcripts differentiated patients with RVA and HTN from three sets of matched controls, with and without HTN and EPO use, with 100% concordance (p < 0.001). The biological processes governed by these significant genes suggest a role for EPO regulation of growth factor receptor ubiquitination as a putative mechanism for renal vascular injury.This study cautions against the use early post-transplant use of EPO in immunosuppression regimens with steroid minimization/avoidance, which may have an increased incidence of post-transplant anemia.
View details for DOI 10.1111/j.1399-0012.2007.00694.x
View details for Web of Science ID 000249320900003
View details for PubMedID 17845633
A retrospective analysis was conducted on 10 consecutive cases of neonatal ARPKD, 9 of whom received kidney transplants (KT). All were diagnosed antenatally (n = 6) or at birth. In the first month of life 70% required ventilatory support. Pre-emptive bilateral nephrectomy and peritoneal dialysis (PD) catheter placement were performed in 9 at a mean age of 7.8 +/- 11.9 months. The indications for nephrectomy were massive kidneys, resulting in suboptimal nutrition and respiratory compromise. All patients received assisted enteral nutrition, with significant increase in mean tolerated feeds following nephrectomy (p < 0.05), with increase in mean normalized weight and height (0.92 and 1.2 delta SDS respectively), by one year post-transplantation. KT was performed at a mean age and weight of 2.5 +/- 1.4 years and 13.3 +/- 6.1 kg. The mean creatinine clearance at one year post-KT was 91.3 +/- 38.1 mls/min/1.73 m(2), with a projected graft life expectancy of 18.4 years. Patient survival was 89% and death censored graft survival was 100%, at a mean follow-up of 6.1 +/- 4.5 years post-transplant. Six patients demonstrated evidence of hepatic fibrosis, one of which required liver transplantation. In patients with massive kidneys from ARPKD, pre-emptive bilateral nephrectomy, supportive PD and early aggressive nutrition, can minimize early infant mortality, so that subsequent KT can be performed with excellent patient and graft survival.
View details for DOI 10.1111/j.1399-3046.2006.00644.x
View details for Web of Science ID 000245415600007
View details for PubMedID 17430481
Post-transplant clinical disease with cytomegalovirus (CMV) and Epstein-Barr virus (EBV) is a known risk factor for graft dysfunction and lymphoproliferation. We postulate that subclinical, asymptomatic viremia also adversely impacts outcomes, and may warrant re-assessment of current monitoring and antiviral prophylaxis protocols. A single-center study was conducted on 102 pediatric (51 steroid-free and 51 matched steroid-based historical controls). Quantitative viral loads were serially monitored and correlated with outcome measures. Overall, the incidence of CMV and EBV clinical disease was 5% (1% CMV and 4% EBV); however, the incidence of subclinical viremia was 44% (12.7% CMV, 38.2% EBV, 6.9% CMV + EBV). Risk factors for subclinical viremia were EBV naivety (p = 0.07), age less than five yr (p = 0.04), lack of prophylaxis (p = 0.01), and steroid usage (p = 0.0007). Subclinical viremia was associated with lower three-yr graft function (p = 0.03), increased risk of acute rejection (odds ratio 2.07; p = 0.025), hypertension (p = 0.04), and graft loss (p = 0.03). Subclinical asymptomatic CMV and EBV viremia is a risk factor for graft injury and loss. These findings support the need for aggressive, serial viral monitoring to better determine the appropriate length of post-transplant antiviral prophylaxis, and to determine the effect of immunosuppression protocols on the development of viremia.
View details for DOI 10.1111/j.1399-3046.2006.00641.x
View details for Web of Science ID 000243792400013
View details for PubMedID 17300499
Calcineurin inhibitor toxicity (CNIT) is an important cause of chronic allograft nephropathy (CAN), but clinically relevant, diagnostic pathologic criteria remain to be defined. A semiquantitative, clinically correlative CNIT scoring system was developed and validated by pathologic analyses of 254 renal transplant biopsies that were obtained from 50 consecutive pediatric renal transplant recipients. Differentially weighted pathologic criteria (glomerulosclerosis, tubular atrophy, arteriolar medial hyaline, and tubular isometric vacuolization) contributed to the composite CNIT model score. Unlike other established pathology chronicity scores, such as the chronic allograft damage index, Banff, and modified Banff, the CNIT score was highly correlated with future graft function. The 3-mo CNIT score correlated significantly with 12 mo (P = 0.021) and 24 mo (P = 0.03) calculated creatinine clearance. Arteriolar medial hyalinosis seems to be the most important factor contributing to the clinical impact of the CNIT score.
View details for DOI 10.2215/CJN.01320406
View details for Web of Science ID 000243324500022
View details for PubMedID 17699397
Although normative values of post-transplant proteinuria have been reported in adults, data for pediatric renal transplant recipients have not been previously published. We hypothesized that pediatric renal transplant recipients achieve normal urinary protein to creatinine (UProt/UCr) ratios (<0.2) by 60 days post-transplant in the absence of early recurrent disease. Retrospective chart review of 108 consecutive pediatric renal transplant recipients at Stanford University was performed. Thirty-two (30%) patients who were eligible had > or = 1 UProt/UCr ratio obtained during the first 60 post-transplant days. Mean age at transplant was 13.9 +/- 4.2 yr. UProt/UCr ratios were grouped by week post-transplant for quantile analysis. Mean weekly UProt/UCr values were not lower than 0.2 until the ninth post-transplant week. No difference in post-transplant proteinuria existed between nephrectomized and non-nephrectomized transplant recipients. Experience with a single patient with proven focal segmental glomerulosclerosis (FSGS) recurrence suggests that normative UProt/UCr data may be useful in early identification of patients experiencing disease recurrence. Univariate correlations demonstrated that UProt/UCr negatively correlated with serum albumin levels (-0.415, p < 0.0001) and days post-transplant (-0.531, p < 0.0001). Independent of primary diagnosis, proteinuria persists throughout the first 60 days in most pediatric renal transplant patients, decreasing relative to time post-transplant.
View details for DOI 10.1111/j.1399-3046.2006.00594.x
View details for Web of Science ID 000241678100016
View details for PubMedID 17096766
Inferior vena cava (IVC) thrombosis is generally a contraindication to renal transplantation in small children because of the technical difficulty and limitations in allograft venous outflow drainage that risk graft thrombosis.The records of six consecutive children (9.9-27.4 kg) with end-stage renal disease and thrombosed IVCs were reviewed. Small deceased donor renal allografts were utilized in all cases where immediate posttransplant venous renal outflow would theoretically not exceed the drainage capacity of the iliac or adjacent pelvic collateral veins.There is 100% patient survival with two patients returning to dialysis at seven and three years posttransplantation. There were no surgical complications or delayed graft function. Postoperatively, progressive renal vein and simultaneous iliac venous enlargement was observed in five of six recipients concomitant with renal allograft enlargement. In these patients, maximum renal volume achieved was between 152 and 275 ml and last recorded Schwartz glomerular filtration rates ranged from 67 to 118 ml/min. The sixth allograft had an early, severe rejection episode that limited renal growth and attainment of good renal function. All patients demonstrated resumption of growth rates commensurate with age but without significant catch-up growth.A small deceased donor kidney can provide freedom from dialysis and better quality of life for small children with IVC thrombosis during an age when dialysis treatment is difficult and the complications of the thrombosed IVC may compromise life. Good renal function was attained in patients without rejection episodes. In those with rejection, our approach allowed for patient growth during allograft function, providing a bridge for a repeat transplant.
View details for DOI 10.1097/01.tp.0000236644.76359.47
View details for Web of Science ID 000242059600007
View details for PubMedID 17102765
Renal transplantation in the pediatric population, although conceptually similar to that in adults, differs in many aspects. This review will focus on the issues unique to the pediatric recipient. In particular, we will focus on the incidence and etiology of end stage renal disease in children, and the results as measured by patient and graft survival. Pretransplant surgical considerations of timing of the transplant, management of congenital urologic abnormalities and the abnormal bladder will be addressed. Etiologies of renal failure unique to the pediatric population will be discussed, including autosomal recessive polycystic kidney disease, congenital nephrotic syndrome, inferior vena cava thrombosis, and primary hyperoxaluria Type 1. Lastly, special transplant surgical considerations including transplantation of an adult-size kidney (ASK) into an infant or small child and ureteral implantation, management of the urinary bladder, and fluid management in infants and small children will be discussed.
View details for PubMedID 16818142
The causes and clinical course of acute rejection vary, and it is not possible to predict graft outcome reliably on the basis of available clinical, pathological, and genetic markers. We hypothesized that previously unrecognized molecular heterogeneity might underlie some of the variability in the clinical course of acute renal allograft rejection and in its response to treatment.We used DNA microarrays in a systematic study of gene-expression patterns in biopsy samples from normal and dysfunctional renal allografts. A combination of exploratory and supervised bioinformatic methods was used to analyze these profiles.We found consistent differences among the gene-expression patterns associated with acute rejection, nephrotoxic effects of drugs, chronic allograft nephropathy, and normal kidneys. The gene-expression patterns associated with acute rejection suggested at least three possible distinct subtypes of acute rejection that, although indistinguishable by light microscopy, were marked by differences in immune activation and cellular proliferation. Since the gene-expression patterns pointed to substantial variation in the composition of immune infiltrates, we used immunohistochemical staining to define these subtypes further. This analysis revealed a striking association between dense CD20+ B-cell infiltrates and both clinical glucocorticoid resistance (P=0.01) and graft loss (P<0.001).Systematic analysis of gene-expression patterns provides a window on the biology and pathogenesis of renal allograft rejection. Biopsy samples from patients with acute rejection that are indistinguishable on conventional histologic analysis reveal extensive differences in gene expression, which are associated with differences in immunologic and cellular features and clinical course. The presence of dense clusters of B cells in a biopsy sample was strongly associated with severe graft rejection, suggesting a pivotal role of infiltrating B cells in acute rejection.
View details for Web of Science ID 000184024400005
View details for PubMedID 12853585
Rodents and dogs conditioned with total-lymphoid irradiation (TLI), with or without antithymocyte globulin (ATG), have been shown to develop mixed chimerism and immune tolerance without graft-versus-host disease (GVHD) after the infusion of major histocompatability complex (MHC)-mismatched donor bone marrow cells given alone or in combination with an organ allograft.Four human leukocyte antigen (HLA)-mismatched recipients of living donor kidney transplants were conditioned with TLI and ATG posttransplantation and infused with cyropreserved donor granulocyte colony-stimulating factor (G-CSF) "mobilized" hematopoietic progenitor (CD34+) cells (3-5x10(6) cells/kg) thereafter. Maintenance prednisone and cyclosporine dosages were tapered, and recipients were monitored for chimerism, GVHD, graft function, T-cell subsets in the blood, and antidonor reactivity in the mixed leukocyte reaction (MLR).Three of the four patients achieved multilineage macrochimerism, with up to 16% of donor-type cells among blood mononuclear cells without evidence of GVHD. Prolonged depletion of CD4+ T cells was observed in all four patients. Rejection episodes were not observed in the three macrochimeric recipients, and immunosuppressive drugs were withdrawn in the first patient by 12 months. Prednisone was withdrawn from a second patient at 9 months, and cyclosporine was tapered thereafter.Multilineage macrochimerism can be achieved without GVHD in HLA-mismatched recipients of combined kidney and hematopoietic progenitor transplants. Conditioning of the host with posttransplant TLI and ATG was nonmyeloablative and was not associated with severe infections. Recipients continue to be studied for the development of immune tolerance.
View details for Web of Science ID 000175933100002
View details for PubMedID 12023614
Corticosteroids have been a cornerstone of immunosuppression for four decades despite their adverse side effects. Past attempts at steroid withdrawal in pediatric renal transplantation have had little success. This study tests the hypothesis that a complete steroid-free immunosuppressive protocol avoids steroid dependency for suppression of the immune response with its accompanying risk of acute rejection on steroid withdrawal.An open labeled prospective study of complete steroid avoidance immunosuppressive protocol was undertaken in 10 unsensitized pediatric recipients (ages 5-21 years; mean 14.4 years) of first renal allografts. Steroids were substituted with extended daclizumab use, in combination with tacrolimus and mycophenolate mofetil. Protocol biopsies were performed in the steroid-free group at 0, 1, 3, 6, and 12 months posttransplantation. Clinical outcomes were compared to a steroid-based group of 37 matched historical controls.Graft and patient survival was 100% in both groups. Clinical acute rejection was absent in the steroid-free group at a mean follow-up time of 9 months (range 3-13.7 months). Protocol biopsies in the steroid-free group (includes 10 patients at 3 months, 7 at 6 months, and 4 at 12 months) revealed only two instances of mild (Banff 1A) subclinical rejection (reversed by only a nominal increase in immunosuppression) and no chronic rejection. At 6 months the steroid-free group had no hypertension requiring treatment (P=0.003), no hypercholesterolemia (P=0.007), and essentially no body disfigurement (P=0.0001). Serum creatinines, Schwartz GFR, and mean delta height Z scores trended better in the steroid-free group. In the steroid-free group, one patient had cytomegalovirus disease at 1 month and three had easily treated herpes simplex stomatitis, but with no significant increase in bacterial infections or rehospitalizations over the steroid-based group. The steroid-free group was more anemic early posttransplantation (P=0.004), suggesting an early role of steroids in erythrogenesis; erythropoietin use normalized hematocrits by 6 months.Complete steroid-free immunosuppression is efficacious and safe in this selected group of children with no early clinical acute rejection episodes. This protocol avoids the morbid side effects of steroids without increasing infection, and may play a future critical role in avoiding noncompliance, although optimizing renal function and growth.
View details for Web of Science ID 000169949100006
View details for PubMedID 11468528
Infants with end-stage renal disease are at highest risk for early graft loss and mortality of any subgroup undergoing renal transplantation. This study evaluates the influence of donor tissue mass and acute tubular necrosis (ATN) on graft survival and incidence of acute rejection episodes in infant and small child recipients of living donor (LD) and cadaver (CAD) adult-size kidneys (ASKs), pediatric CAD kidneys and combined kidney-liver transplants. Methods. Kidney transplants in infants and small children at a single center and those reported to the UNOS Scientific Renal Transplant Registry were analyzed. At Stanford, multi-variate analysis was conducted on 45 consecutive renal allograft recipients weighing < or = 15 kg, mean weight 11.2 +/- 2.6 kg. The UNOS Registry results in age groups 0-2.5 (n=548) and 2.5-5 years (n=743) were compared with age groups 6-12, 13-18, and the lowest risk adult group of 19-45 years. STANFORD RESULTS. Graft survival was 97.8 +/- 0.0 at 2 years and 84.6 +/- 0.1% at 8 years. The incidence of biopsy proven rejection was 8.8% in the first 3 months and 15.5% over the 8-year follow-up. None of the pediatric CAD kidneys had ATN. Rejection episodes were restricted to the pediatric CAD kidneys alone (3/3), with no kidney rejections in the combined pediatric CAD kidney-liver transplants (0/6; P=0.003). Four ASK transplants had ATN (1 postoperative and 3 late), and all predisposed to subsequent acute rejection episodes (4/4), whereas there were no rejection episodes in ASK transplants without ATN (0/32; P<0.001). At 3 years posttransplantation, mean serum creatinines were worse in ASKs with ATN (1.5 vs. 0.9 mg/dL; P<0.001) and in all grafts with rejection episodes (1.2 vs. 0.9 mg/dL; P<0.05). UNOS RESULTS: Among the 5 age groups studied, significantly better (P<0.001) long-term graft survival rates were observed in allograft recipients in the 2 youngest age groups with ASKs without ATN: 82 +/- 3% and 81 +/- 3% for LD and 70 +/- 7% and 78 +/- 4% for CAD recipients in the 0-2.5 and 2.5- to 5-year age groups, respectively, at 6 years after transplantation. Moreover, the projected graft half-lives after the 1st year in the LD groups without ATN were at least equivalent to those of HLA-identical sibling recipients ages 19-45 years: 26.3 +/- 5 and 29.3 +/- 6 years for the 0- to 2.5- and 2.5- to 5-year age groups, respectively, and 23.3 +/- 1 years for HLA-identical transplants. The graft half-lives for CAD recipients without ATN ages 0-2.5 and 2.5-5 yearswere equivalent or better than those for LD transplants without ATN in recipients aged 19-45 years: 15.4+/- 7 and 23.7 +/- 8 years versus 15.0 +/- 0.3 years. Mean serum creatinines were superior in the 2 younger recipient age groups compared with older age groups.Increased donor tissue mass of the ASK or kidney-liver transplants, in the absence of ATN, seems to confer a protective effect to infant and small child recipients of these allografts. This is manifested by a prolonged rejection-free state in the single center experience and enhanced graft survival and function in the UNOS analysis, comparable to HLA identical sibling transplants for LD infant and small child recipients and to LD adult results for CAD infant and small child recipients. To optimize this protective effect by whatever mechanism, absolute avoidance of ATN is essential in infant recipients of ASK or combined kidney-liver transplants.
View details for Web of Science ID 000166206200012
View details for PubMedID 11152105
Infants make up the most high-risk, difficult to care for subgroup undergoing kidney transplantation, with the lowest 1- and 2-year graft survival rates of any other age group. The principal causes of graft loss have been graft thrombosis, primary nonfunction, technical error, and irreversible acute rejection.Infants undergoing kidney transplantation can achieve near 100% graft survival at 2 years following surgery, despite their very high-risk status.Analysis of 45 consecutive kidney transplants performed in patients weighing less than or equal to 15 kg during an 8-year period beginning August 1991. Patients included complex referrals from throughout the United States and all received transplants and were cared for by the same pediatric kidney transplantation team.Mean weight at transplantation was 11. 2 kg. Renal failure was due to congenital or urologic causes in the majority (53%) of cases. Size-discrepant adult-sized kidney grafts were transplanted in 80% of patients; 64% received live-donor grafts; 78% were receiving dialysis prior to transplantation; and 27% had extremely small bladders (<20 cm(3)) requiring modification of the ureteral implantation. Excluding 1 transplant-unrelated death, graft and patient survival at 2 years was 100%. Eight-year patient and graft survival rates (for our combined live and cadaver donor series) were 89.6% and 84.6%, respectively. This compares favorably with much lower graft survival in low-risk adult recipients. Delayed graft function occurred in only 1 patient (2%). Rate of incidence of rejection was 9.3% within 2 years of transplantation and the overall rejection rate was 15.5%. No graft was lost to vascular thrombosis, primary nonfunction, technical error, or acute rejection. The mean creatinine level was 53.04 micromol/L (0.6 mg/dL) and 61.9 micromol/L (0.7 mg/dL) at 1 and 2 years, respectively, and 88.4 micromol/L (1.0 mg/dL) at 3, 4, and 5 years after transplantation.One hundred percent 2-year and excellent 8-year graft survival rates can be achieved in what has historically been the highest-risk and most difficult to care for patient subgroup undergoing kidney transplantation.
View details for Web of Science ID 000089222400017
View details for PubMedID 10982511
View details for Web of Science ID 000088863300003
View details for PubMedID 10949179
Major, almost insurmountable, deterrents exist to the use of the small capacity, defunctionalized, nonneurogenic urinary bladder in renal transplantation, namely, the technical difficulty in performing a satisfactory ureteral implantation with conventional methods and the potential secondary problems with high grade ureteral reflux and obstruction. Alternatives are less than ideal and include transplantation into a bowel-augmented urinary bladder with intermittent self-catheterization, ileal conduit urinary diversion, or avoidance of transplantation and relegating the patient to life-long dialysis.Eight consecutive patients (ages 13 months to 29 years) with small, defunctionalized urinary bladders underwent a new method of intravesical implantation of the transplant ureter. The mean capacity of these bladders was 18.5+/-13.1 ml (range 6 to 45 ml), with the bladders defunctionalized for a mean 81.6+/-24.3% of the patients' total lifetime. The technique involved placement of the transplant ureter into a shallow, mucosa-denuded, rectangular trough extending from a superiorly placed ureteral hiatus distally to the trigone. We hypothesized that the mucosal margins on the two lateral aspects of the rectangular trough would grow over the anterior surface of the ureter until they met the advancing mucosal edges from the contralateral side to form a natural neosubmucosal tunnel.Posttransplantation cystoscopic examination demonstrated bladder mucosal regeneration and growth over the ureter, confirming the spontaneous development of a good length neosubmucosal tunnel. All patients demonstrated no evidence of ureteral reflux or ureteral obstruction, whereas an immediate prior cohort of four consecutive patients with bladder capacities < or =30 ml showed that three of four had ureteral reflux (P=0.02) and four of four developed hydronephrosis (P=0.002). All urinary bladders in the present cohort enlarged to expected normal or nearnormal capacities. Serum creatinines were stable throughout the entire follow-up period, with the exception of one patient who had rejection episodes. Two patients had urinary tract infections posttransplantation, but there were no episodes of acute pyelonephritis.This novel technique for ureteral implantation successfully capitalizes on the regenerative potential of the bladder mucosa, resulting in a physiological, anatomically natural, and very effective neosubmucosal tunnel. It appears to guarantee success against both ureteral reflux and obstruction, no matter how small the urinary bladder, and offers no hindrance to enlarging the bladder to near normal capacity posttransplantation. The implantation technique is simple and safe, and its use should eliminate the reluctance to use these bladders. Moreover, this procedure offers a major incentive for the successful rehabilitation of small, defunctionalized, nonneurogenic bladders after kidney transplantation.
View details for Web of Science ID 000082889100004
View details for PubMedID 10515372
Nationally, results of renal transplantation in infants are inferior to those in older children and adults. Within the infant group, best results are obtained with adult-sized kidneys (ASKs) rather than size-compatible pediatric kidneys. However, transplantation of ASKs into infants has an increased risk of acute tubular necrosis and graft loss from vascular thrombosis and primary nonfunction. The aim of this study was to define and understand the hemodynamic changes induced by ASK transplantation, so that outcomes of transplantation in infants can be improved.Nine hemodynamically stable and optimally hydrated infants were studied under a controlled sedation with cine phase-contrast magnetic resonance at three time periods: before transplantation, 8-12 days after transplantation, and 4-6 months after transplantation. Cross-sectional images of both the infant aorta and the adult transplant renal artery were obtained and blood flow was quantitated. Renal volumes were also obtained, and expected renal artery blood flow based on early posttransplant volume was calculated. In addition, renal artery blood flow was determined in 10 in situ native adult kidneys prior to donor nephrectomy. Supplemental nasogastric or gastrostomy tube feeding was carried out during the blood flow study period to optimize intravascular volume.Mean infant aortic blood flows were 331+/-148 ml/min before transplantation, 761+/-272 ml/ min at 8-12 days after transplantation (P=0.0006 with pretransplant flow), and 665+/-138 ml/min at 4-6 months after transplantation (P=0.0001 with pretransplant flow). Mean transplanted renal artery flows were 385+/-158 ml/min at 8-12 days and 296+/-113 ml/min at 4-6 months after transplantation. Transplanted renal artery flows were less than prenephrectomy in situ donor renal artery blood flow (618+/-130 ml/min; P=0.02 and P=0.0003) and expected normal renal artery blood flow (666+/-87 ml/min; P=0.003 and P=0.001) at both 8-12 days and 4-6 months after transplantation. A 26% reduction in renal volume (P=0.003) occurred between the two postoperative time periods, and this paralleled the decrease in posttransplant renal artery flow. One-year graft and patient survival in the nine infants was 100%. The mean serum creatinine levels at 3, 6, and 12 months were 0.43+/-0.10, 0.48+/-0.15, and 0.49+/-0.16 mg/dl.This study is the first to quantitatively document the blood flow changes occurring after ASK transplantation in infants. There was a greater than two-fold increase in aortic blood flow after ASK transplantation, and this increase was sustained for at least 4 months and appeared to be driven by the blood flow demand of the ASK. However, actual posttransplant renal artery blood flow was significantly less than normal renal artery flow. Our study suggests that aggressive intravascular volume maintenance may be necessary to achieve and maintain optimum aortic blood flow, so as not to further compromise posttransplant renal artery flow and to avoid low-flow states that could induce acute tubular necrosis, vascular thrombosis, or primary nonfunction.
View details for Web of Science ID 000076585400001
View details for PubMedID 9798687
View details for Web of Science ID A1991GK78900170
View details for PubMedID 1656566


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Massive congratulations to Philip George and Anton Powers whose single "Alone No More" just smashed into the UK official chart at Number 4…this week's highest new entry! The lads joined Radio 1's Chart Show host Greg James in studio for a quick chat about their success.
There's some stiff competition at the top of the chart, but we're betting that Philip & Anton will climb even higher next week!
If you didn't get the single already, download it here. Remixes come courtesy of Dexcell, Etherwood, Ferreck Dawn, Midnight City, Tazer, Tom Zanetti & K.O Kane and you can grab them here. You can also hear "Alone No More" on Spotify.
Check out the official video: