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 progressio n of renal disease was examined in patients with Type II (non-insulin-depen dent) diabetes and microalbuminuria (urinary albumin-to-creatinine ratio = 30-299 mg/g). Methods. Kidney biopsy specimens were obtained from 16 diabetic Pima Indian s (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 c omputing the change in urinary albumin excretion during the study (Delta UA E). 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 625m g/g (range = 9-13471mg/g) after 4 years; 10 subjects (63%; 4 men, 6 women) developed macroalbuminuria (urinary albumin-to-creatinine ratio greater tha n or equal to 300 mg/g). Neither mean arterial pressure nor HbA(1c) changed substantially during follow-up. Among the glomerular morphologic character istics, the number of visceral epithelial cells, or podocytes, per glomerul us 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 predi cting more rapid progression. Glomerular basement membrane thickness did no t 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 ye ars) r = 0.42, p = 0.11; Delta UAE, r = 0.48,p = 0.06). Conclusion/interpretation. Whether lower epithelial cell number per glomeru lus among those that progressed was due to cellular destruction, a reduced complement of epithelial cells, or both is uncertain. Nevertheless, these f indings suggest that podocytes play an important part in the development an d progression of diabetic renal disease.