Abstract
BackgroundWhile histopathologic changes correlate with functional impairment in cross-sectional studies of diabetic nephropathy (DN), whether these findings predict future rate of kidney function loss remains uncertain. We thus sought to examine the relationship between kidney histopathology, incidence of end-stage kidney disease (ESKD), and rate of estimated glomerular filtration rate (eGFR) loss in DN.MethodsIn this longitudinal cohort study, we studied 50 adults diagnosed with biopsy-proven DN. We analyzed the histopathologic parameters of each patient’s kidney biopsy, as defined by the Renal Pathology Society classification system for DN, and tracked all available eGFR measurements post-biopsy. We additionally collected baseline clinical parameters (at the time of biopsy), including eGFR, albumin-to-creatinine ratio (ACR), and hemoglobin A1c. Multivariable linear regression was used to assess the relationship between histologic and clinical parameters at the time of the biopsy and eGFR slope. Kaplan-Meier curves and Cox regression were used to evaluate the association between histologic and clinical parameters and ESKD incidence.ResultsProgression to ESKD was associated with worsening interstitial fibrosis score (p = 0.05), lower baseline eGFR (p = 0.02), higher ACR (p = 0.001), and faster eGFR decline (p < 0.001). The rate of eGFR decline did not associate with any histologic parameter. Baseline ACR was the only studied variable correlating with eGFR slope (rho = − 0.41).ConclusionsRenal histology predicts ultimate progression to ESKD, but not the rate of progression. Future work is required to identify novel predictors of rapid functional decline in patients with diabetic nephropathy.
Highlights
While histopathologic changes correlate with functional impairment in cross-sectional studies of diabetic nephropathy (DN), whether these findings predict future rate of kidney function loss remains uncertain
Established disease, but not the rate of disease progression. Both interstitial fibrosis and tubular atrophy (IF/TA) and glomerular injury classes correlated closely with baseline estimated glomerular filtration rate (eGFR). These results suggest that: (1) Renal Pathological Society (RPS) histology injury scores do not predict future rate of eGFR loss, and (2) even standard clinical parameters such as albumin-to-creatinine ratio (ACR) and HbA1c are only modestly associated with rate of eGFR loss
We considered the outcomes of renal survival and eGFR change over time separately, and unexpectedly found that IF/TA scores were associated with progression to end-stage kidney disease (ESKD), but did not predict the rate of eGFR loss
Summary
While histopathologic changes correlate with functional impairment in cross-sectional studies of diabetic nephropathy (DN), whether these findings predict future rate of kidney function loss remains uncertain. With nearly one in every ten Americans diagnosed with diabetes, diabetic nephropathy (DN) has become the most common cause of kidney failure in the United States [1, 2] Despite this alarming statistic, most patients with diabetes do not develop kidney failure, and many develop only mild renal dysfunction [3, 4]. While a number of high risk clinical features such as hypertension, high-grade albuminuria, and poor glycemic control are well established [6, 8], our ability to measure the rate of kidney function loss in DN and identify “rapid progressors” remains limited [9]. Understanding the factors that influence rate of eGFR decline could help predict the clinical course for individual patients and help identify rapid progressors for studies of novel renoprotective agents
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