Podocyte number predicts long-term urinary albumin excretion in Pima Indians with Type II diabetes and microalbuminuria

Aims/hypothesis. The predictive value of glomerular structure on progression of renal disease was examined in patients with Type II (non-insulin-dependent) diabetes and microalbuminuria (urinary albumin-to-creatinine ratio = 30-299 mg/g). Methods. Kidney biopsy specimens were obtained from 16 diabetic Pima Indians (6 men, 10 women). Progression of renal disease was assessed by measuring urinary albumin excretion 4 years after the biopsy (UAE(4 years)) and by computing the change in urinary albumin excretion during the study (Delta UAE). Results. At baseline, the duration of diabetes averaged 13.3 years (range = 4.0-23.8 years) and the mean glomerular filtration rate was 159 ml . min(-1) . 1.73m(-2) (range = 98 - 239 ml . min(-1) . 1.73m(-2)). Median urinary albumin excretion was 67mg/g (range = 25-136 mg/g) and it increased to 625mg/g (range = 9-13471mg/g) after 4 years; 10 subjects (63%; 4 men, 6 women) developed macroalbuminuria (urinary albumin-to-creatinine ratio greater than or equal to 300 mg/g). Neither mean arterial pressure nor HbA(1c) changed substantially during follow-up. Among the glomerular morphologic characteristics, the number of visceral epithelial cells, or podocytes, per glomerulus was the strongest predictor of renal disease progression (UAE(4 years) r = -0.49, p = 0.05; Delta UAE, r = -0.57, p = 0.02), with fewer cells predicting more rapid progression. Glomerular basement membrane thickness did not predict progression (UAE(4 years) r = 0.11, p = 0.67; Delta UAE, r = 0.09,p = 0.73) and mesangial volume fraction had only a modest effect (UAE(4 years) r = 0.42, p = 0.11; Delta UAE, r = 0.48,p = 0.06). Conclusion/interpretation. Whether lower epithelial cell number per glomerulus among those that progressed was due to cellular destruction, a reduced complement of epithelial cells, or both is uncertain. Nevertheless, these findings suggest that podocytes play an important part in the development and progression of diabetic renal disease.