Urinary sulphate excretion and progression of diabetic nephropathy in Type1 diabetes

Aims Hydrogen sulphide levels are reduced in many disease states, including diabetes and end-stage renal disease. We aimed to determine whether urinary sulphate excretion, as a proxy for hydrogen sulphide, was associated with progression of diabetic nephropathy. Methods We conducted a post-hoc study of a prospective, randomized, controlled trial on the effect of a low vs. normal protein diet for 4years, on decline of renal function in patients with Type1 diabetes and diabetic nephropathy. We excluded patients with less than three measurements of glomerular filtration rate assessed by 51Cr-EDTA plasma clearance (GFR) and less than 1year of follow-up (n=10), leaving 72 patients eligible for analyses. We studied both association of rate of decline in GFR and association of the combined endpoint of end-stage renal disease and death with baseline 24-h urinary sulphate excretion. Results Sulphate excretion was significantly associated with the slope of GFR (rs=0.28, P=0.02). In a multivariate regression model, sulphate excretion was a significant determinant of decline in GFR, independent of age, gender, blood pressure, HbA1c, smoking, albuminuria, baseline GFR and diet group (P<0.01). In addition, adjusted r2 increased from 5% in a model with the aforementioned risk factors to 22% when sulphate excretion was included in the model. Cox regression revealed a hazard ratio of 0.34 (95%CI 0.130.88, P=0.026) for each natural log unit increase in urinary sulphate excretion. Conclusion High urinary sulphate excretion was significantly associated with slower decline in 51Cr-EDTA-assessed GFR in diabetic nephropathy, independent of known progression promoters.