Urinary sulphate excretion and progression of diabetic nephropathy in Type 1 diabetes

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.

We conducted a post-hoc study of a prospective, randomized, controlled trial on the effect of a low vs. normal protein diet for 4 years, on decline of renal function in patients with Type 1 diabetes and diabetic nephropathy. We excluded patients with less than three measurements of glomerular filtration rate assessed by (51)Cr-EDTA plasma clearance (GFR) and less than 1 year 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.

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 r(2) 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 0.13-0.88, P = 0.026) for each natural log unit increase in urinary sulphate excretion.

High urinary sulphate excretion was significantly associated with slower decline in (51)Cr-EDTA-assessed GFR in diabetic nephropathy, independent of known progression promoters.