The biological consequences of chronic consumption of Maillard reaction products (MRPs) on renal function in health and renal disease are still incompletely understood. We investigated the metabolic and renal effects of a diet with varying MRP content in healthy and subtotally nephrectomized rats. Male Wistar rats were subjected to sham operation (control, C, n = 12), or to 5/6 nephrectomy (5/6NX, n = 12). Both groups were randomized into subgroups and pair-fed with either a MRP-poor or -rich diet for six weeks. The diet was prepared by replacing 5% or 25% of wheat starch by bread crust (BC). In spite of pair-feeding, the rats on the 25% BC diet gained more body weight (C: 183 +/- 6 g; C + 5% BC: 197 +/- 7 g; C + 25% BC: 229 +/- 6 g [P < 0.05]; 5/6NX: 165 +/- 10 g; 5/6NX + 5% BC: 202 +/- 3 g; 5/6NX + 25% BC: 209 +/- 8 g [P < 0.05]) and had a higher organ weight (heart, liver, lung, kidney/remnant kidney). Bread crust-enriched diet induced proteinuria (C: 15 +/- 5 mg/24 h; C + 5% BC: 19 +/- 4; C + 25% BC: 26 +/- 3 [P < 0.05]; 5/6NX: 30 +/- 7 mg/24 h; 5/6NX + 5% BC: 47 +/- 9; 5/6NX + 25% BC: 87 +/- 19 [P < 0.01]) and a rise in urinary transforming growth factor beta(1) excretion (C: 0.4 +/- 0.1 ng/24 h; C + 5% BC: 0.6 +/- 0.1; C + 25% BC: 1.2 +/- 0.3; 5/6NX: 0.5 +/- 0.1 ng/24 h; 5/6NX + 5% BC: 0.9 +/- 0.1; 5/6NX + 25% BC: 1.6 +/- 0.2 [P < 0.01]). Plasma creatinine or creatinine clearance were not affected significantly. In conclusion, our data suggests that long-term consumption of a diet rich in MRPs may lead to damage of the kidneys.