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Reply to: Kidney Dysfunction and Risk of Parkinson's Disease: The Issue of Equations and Large Number”

We appreciate Castillo-Torres and colleagues for their interest and valuable comments on our study. We reported a positive association between chronic renal dysfunction and risk of Parkinson’s disease (PD) among large samples of individuals aged ≥65 years based on the Korean National Health Insurance Service Checkup data. We used an estimated glomerular filtration rate (GFR) based on the Modification of Diet in Renal Disease (MDRD) calculation to estimate renal function and also used the results of dipstick tests to support the results. The use of MDRD and Chronic Kidney Disease Epidemiology Collaboration formula has been recommended for diagnosis and care of patients with chronic kidney disease. GFR estimates had given very different results in elderly patients; thus, it is of concern which equation should be used in this population. Although none of those equations have been validated in a very elderly population, both equations seem to be preferred, even in old and very old patients according to studies. Albumin-tocreatinine ratio or protein-to-creatinine ratio in urine is superior for quantifying the degree of proteinuria and is recommended for this purpose. However, these measurements could not be available in our study based on large-scale nationwide checkup data. The urine dipstick test also has high sensitivity and specificity in screening for proteinuria and is suggested as a useful surrogate marker for low-grade albuminuria and glomerular endothelial dysfunction. Dipstick proteinuria ≥1+ was found to be reliable for the detection of significant proteinuria in elderly Korean individuals. Large studies based on big data are suggested to be more reliable than smaller studies. However, it is necessary to interpret the findings from big data with caution because there may be a variety of bias. Information on disease diagnosis in our study based on big data analysis may not be optimal because the data have been collected for medical service claims and reimbursement. We recognize that there may be overestimation of PD diagnosis when it is based on only an International Classification of Diseases Tenth Revision (ICD-10) code (G20) of PD. However, the program for copayment reduction enables relatively accurate diagnosis because the Korean government supervises the program and supports substantial medical expenses for such intractable disease. Although there was no validation study for this issue and, moreover, the operational definition cannot distinguish atypical PD or drug-induced parkinsonism, we can give some answers indirectly from following results from an additional analysis. Of 106,885 individuals who were claimed for G20 of ICD-10 code from our data set in 2010, 59,768 individuals (55.9%) were also claimed for a copayment registration code (V124). Of these individuals, after excluding 8371 individuals who were not followed up because of death and so on, 49,149 individuals (95.6%) were reregistered as both G20 and V124, in 2011. This finding shows that our operational diagnosis for PD may have high diagnostic accuracy for PD.