Mitochondrial derangement: Possible initiator of microalbuminuria in NIDDM

Morphometric analysis of 80 renal biopsy specimens from patients with non-insulin-dependent diabetes mellitus, who had been classified into four groups by grade of proteinuria and renal function, revealed mitochondrial enlargement in the proximal tubules, with cellular hypertrophy as an initial morphologic change in the microalbuminuria. This was followed by a thickening of the proximal tubular basement membrane and an increased interstitial volume, causing persistent overt proteinuria. Glomerular nodular and sclerotic lesions and severe tubulointerstitial damage became evident in the advanced stages. As an initial cause of microalbuminuria, the mitochondrial abnormality disturbed adenosine triphosphate (ATP) metabolism in proximal tubules, reducing active transport and causing urinary excretion of low-molecular-weight protein.