Endocrine Abstracts

Introduction: The aetiology of obesity-related nephropathy (ORN) is uncertain but may involve hyperfiltration and systemic inflammation.

Aims: To define ORN using novel urinary biomarkers that can identify damage to specific regions of the nephron.

Methods: Clinical data, blood and urine samples were collected from a consecutive series of 22 patients attending a weight-management clinic (excluding those with diabetes), and from a control group of 19 healthy volunteers. Urine samples were assayed for biomarkers of glomerular fibrosis (collagen IV), proximal tubular damage (alpha GST) and distal tubular damage (Pi GST) by Biotrin. Results are in μg/mmol urinary creatinine.

Results: The control group had mean age 35 years, 15/19 were male, mean weight 77.9 kg. Five obese subjects had diabetes. The remaining 17 obese subjects had mean age 44 years, 7/17 were male, median BMI was 45 kg/m² (range 35–78), all had normal serum creatinine (mean 75.1 μmol/l) and eGFR (mean 90.3 ml/min). One patient had acute renal failure requiring temporary renal dialysis 3 months prior to the study. Compared to the control group 4/17 obese patients (24%) had elevated urinary collagen IV (median 0.32, range 0.11-0.69, control 0.16, range 0.07-0.43, P<0.05). Five of 17 obese patients (29%) had elevated urinary Pi GST (median 3.0, range 0.56–31.1, control 1.26, range 0.0–5.2, P<0.001), whilst 10/17 obese patients (59%) had elevated urinary alpha GST (median 0.95, range 0.2-2.98, control 0.46, range 0.01–0.79, P<0.0005). The patient requiring temporary dialysis had elevated collagen IV (12.2, control<0.43) and grossly elevated pi GST (203.5, control<5.2).

Conclusion: In patients with obesity and normal serum creatinine there is a high prevalence of detectable renal damage compared to a healthy control group that was 9 years younger. This ORN appears to be more related to the proximal renal tubule rather than the glomerulus or distal tubule. This suggests alternative mechanisms to hyperfiltration as the cause of obesity-related nephropathy.