Response to "Letter Regarding Normal Albuminuria in Patients With Autopsy-Proven Advanced Diabetic Nephropathy".

The Authors Reply:

We thank Heyman et al. for their letter regarding our article reporting the association between albuminuria levels and pathologic diabetic nephropathy from a Japanese community-based study. They suggest further evaluating the association between albuminuria and the extent of tubulointerstitial lesions because much of the albumin filtered by the glomeruli is reabsorbed and degraded in the tubules even in physiological status. We agree that tubulointerstitial lesions are important. Therefore, we semiquantitatively evaluated the extent of tubulointerstitial lesions, including interstitial fibrosis/tubular atrophy and interstitial inflammation, and found that as the urinary albumin-to-creatinine ratio levels increased from <30.0, 30 to 299.9, and ≥300.0 mg/g, the extent of tubulointerstitial lesions significantly increased, as illustrated in Figure 2 reported in Sasaki et al. Furthermore, in line with the suggestion of Heyman et al., we further evaluated the association between the urinary albumin-to-creatinine ratio levels and the extent of tubulointerstitial lesions among the autopsied cases with normoalbuminuria (urinary albumin-to-creatinine ratio <30 mg/g, [n = 41]). Nevertheless, this additional analysis did not provide evidence of a significant association between the urinary albumin-to-creatinine ratio levels and the extent of tubulointerstitial lesions (Figure 1). Therefore, these results do not rule out the possibility that the protein leakage associated with glomerular lesions may be masked in cases with normoalbuminuria because the function of reabsorption and degradation in the tubules is preserved owing to relatively mild tubulointerstitial lesions. Nevertheless, given the limited sample size and the influence of postmortem changes in autopsy samples, it would be difficult to prove this issue in our study.

Figure 1

Box- and dot-plots of the extent of the pathologic index for tubulointerstitial lesions according to urinary albumin-to-creatinine ratio levels among the autopsied diabetic cases with normoalbuminuria. (a) IFTA; (b) interstitial inflammation. The bold horizontal line represents the median, the box represents the 25th to 75th percentiles, the vertical bar represents the minimum to the maximum except for outliers, and the dots represent individual cases. Trends in the difference across albuminuria levels were tested by using a Jonckheere-Terpstra test. IFTA, interstitial fibrosis and tubular atrophy.