Single-Nephron GFR in Patients With Obesity-Related Glomerulopathy

Abstract

Introduction: Obesity-related glomerulopathy (ORG) is a slowly progressive kidney disease occurring in association with obesity. It is characterized histopathologically by glomerulomegaly, likely caused by single-nephron hyperfiltration that has not been demonstrated in humans because of technical difficulty in measuring single-nephron glomerular filtration rate (SNGFR) in the clinical setting. Methods: Total glomerular number per kidney, with or without global glomerulosclerosis, was estimated by the combination of cortical volume assessment via unenhanced computed tomography and biopsybased stereology. Mean glomerular volume was calculated from the measured area of glomerular tufts. Both SNGFR and single-nephron urinary protein excretion (SNUPE) were estimated by dividing values for estimated glomerular filtration rate and urinary protein excretion by the number of nonsclerotic glomeruli. Living kidney donors were used as healthy controls. Results: A total of 48 ORG patients with average nonsclerotic glomerular numbers of 456,000 AE 235,000 per kidney were included. The values for SNGFR in ORG patients with chronic kidney disease (CKD) stages 1 and 2 were higher than for nonobese and obese controls (97 AE 43 vs. 59 AE 21 vs. 64 AE 21 nl/min, respectively, P ¼ 0.001). Nonsclerotic glomerular number decreased with advancing stages of renal functional impairment. The presence of ORG with more advanced CKD stages was associated with lower SNGFR and marked elevation in SNUPE levels, with no difference in the mean glomerular volume between the stages. Conclusions: These results provide functional evidence for single-nephron hyperfiltration in patients with ORG, and identify compensatory failure to maintain effective SNGFR as a feature of advanced-stage ORG.

The Renal Pathology of Obesity: Structure-Function Correlations

“…Although obesity usually is defined as a BMI value of 30 kg/m 2 or greater, some studies from Asia used a threshold of BMI values of 28 kg/m 2 or greater in Chinese patients 10 or 25 kg/m 2 or greater in Japanese patients 25,26 for the diagnosis of ORG. In a Columbia University study, the mean BMI of patients with ORG was 41.7 kg/ m 2 ; 46% with class 1 or 2 obesity (BMI, ≥30 to <40 kg/ m 2 ) and 54% in patients with class 3 obesity (BMI, ≥40 kg/m 2 ).…”

Response to Obesity-Related Glomerulopathy: Hyperfiltration may Contribute to early Proteinuria

“…1 for their letter regarding our article reporting the single-nephron GFR in patients with obesity-related glomerulopathy (ORG). 2 Glomerulomegaly with focal segmental glomerulosclerosis of perihilar location is a typical renal histopathological finding in ORG, which has long-been considered to represent a state of single-nephron glomerular hyperfiltration. Our results demonstrated single-nephron hyperfiltration in ORG patients and were consistent with the hypothesis of podocyte failure due to intraglomerular hypertension.…”

Obesity-Related Glomerulopathy: Hyperfiltration May Contribute to Early Proteinuria

“…and Denic and Glassock’s editorial. 1 , 2 Clinicopathological features of ORG include initial glomerulomegaly, podocyte failure and glomerulosclerosis. Marked proteinuria occurs even in early ORG, 874±770 mg/day compared with 29±41 in obese renal donors, an approximately 30-fold increase (CKD Stages 1 and 2, Table 2).…”

“…We read with great interest the paper on Obesity-Related Glomerulopathy (ORG) and Single-Nephron GFR (SNGFR) by Okabayashi et al and Denic and Glassock's editorial 1,2 . Clinicopathological features of ORG include initial glomerulomegaly, podocyte failure and glomerulosclerosis.…”