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Recovery from “End-Stage” Renal Disease

In 1993, we published the results of a large study (1) and a review article (2) on a rather uncommon event: renal function recovery (RFR) enabling patients to discontinue maintenance dialysis. Excluding patients who had been on dialysis for less than 6 weeks and those who had returned to dialysis within 3 months after recovery, we found an incidence of RFR of 2.4% in the Canadian Organ Replacement Register (1). This was well within the 1% to 4% range reported in other large studies published between 1983 and 1992 (3-5). None of these figures has been updated since; for example, the matter of RFR has not been dealt with in any of the annual reports of the European Dialysis and Transplant Association published since 1983. In fact, a Medline search of the English-written literature allowed us to find only one publication on RFR in maintenance dialysis patients for 1994 and 1995, and this was a case report (6). Although the subject appears to have drawn little attention recently, RFR has utmost consequences for the few patients who experience it, even though about half of them eventually return to dialysis (1, 4). Moreover, the likelihood of RFR for a given patient must be taken into account when planning for renal transplantation, which it is better to postpone in patients whose underlying renal damage may heal with time. Thus, awareness of this phenomenon is required by anyone caring for end-stage renal disease patients. Any mention by the patient of an increase in urine output or any reduction in pre-dialysis (or, in the case of continuous peritoneal dialysis, steady state) serum creatinine should arouse suspicion of RFR and indicate the need for a more precise measurement of residual renal function. The nature of the disease that caused the renal failure is by far the most important predictive factor for RFR (1-5). Apart from protracted drug-induced acute renal failure and the myeloma kidney after chemotherapy, which not surprisingly rank high among recovery-prone nephropathies in ESRD registries (1, 4), microvascular diseases are those most frequently associated with RFR. This group includes malignant nephrosclerosis, renal scleroderma and the chronic form of the hemolytic-uremic syndrome (HUS), diseases which share a common lesion of marked intimal proliferation that appears to result at least partly from a trophic effect of high levels of angiotensin II (7). The use of angiotensin-converting enzyme (ACE) inhibitors in such a setting of microvascular renal disease has been associated with RFR in numerous reports (2, 8-14). However, clear-cut evidence in favor of a higher rate of RFR in relation to a specific healing effect of ACE inhibitors, beyond blood pressure control per se, is available only in the case of the renal scleroderma crisis, in which a RFR rate of more than 50% has been reported in survivors using these drugs (12). No comparative studies are available to prove that using ACE inhibitors during the early period of dialysis will favor RFR in malignant nephrosclerosis or chronic HUS, although we have presented some evidence that recoveries may at least be more lasting in the latter disease when patients are treated with ACE inhibitors (2). These drugs may also exert a renal protective effect before ESRD develops in these and other forms or renal microangiopathy (15). Other less influential factors predictive of RFR are age, gender, race, kidney size, residual urine output, dialysis modality and comorbid conditions (2). Despite some conflicting data (4, 5), RFR appears to be more common and more lasting in younger (i.e. under the age of 45) female patients (1). Caucasian patients more often experienced recovery than African-American patients in two U.S. studies (4, 5). Chances of RFR appear better with normal-sized kidneys and a good urine output, but neither is an absolute prerequisite (2). Surprisingly, despite some conflicting data and proof of better preservation of residual renal function in continuous ambulatory peritoneal dialysis than in hemodialysis (16), the probability of being able to stop dialysis may be slightly higher with the latter modality (1). Finally, in the setting of borderline renal function, comorbid factors such as use of nonsteroidal antiinflammatory drugs or decompensated heart failure may set the stage for initiation of dialysis (16). In some of these cases, it may take months before renal function recovers sufficiently to allow discontinuance of dialysis. Large prospective trials would be needed to evaluate any intervention (e.g. ACE inhibition) aimed at increasing the likelihood of RFR among new end-stage renal failure patients. In the meanwhile, beside being more aware of the possibility of RFR, what else can