Effects of acetazolamide on kidney function in Type 1 (insulin-dependent) diabetic patients with diabetic nephropathy

Abstract

Summary. We investigated the effects of 3 days treatment with acetazolamide 250 mg three times daily on kidney function in 8 Type 1 (insulin-dependent) diabetic patients with nephropathy, and in 7 healthy subjects in a doubleblind placebo controlled cross-over study. Glomerular filtration rate and extracellular fluid volume were measured with the single injection 5tCr-EDTA technique and fluid flow rate from the proximal tubules was determined by measurement of the renal lithium clearance. A 24% decline in glomerular filtration rate was observed in both groups during acetazolamide treatment (control subjects: 108 + 11 vs 82 + 9 ml/min, p<0.02, diabetic patients: 71-+19 vs 54+14ml/min, p <0.01). The renal lithium clearance (ml/min) remained about the same (control subjects: 22 -+ 6 vs 27 + 8, NS, diabetic patients: 14_+ 5 vs 15 + 4, NS). Absolute proximal tubular reabsorption of water (ml/min) was reduced by about onethird (control subjects: 85+11 vs 56-+7, p<0.02, diabetic patients: 55 + 17 vs 37+ 6, p < 0.02), and fractional proximal reabsorption of water and sodium (%) declined (control subjects: 79 + 5 vs 67_+ 8, p <0.02, diabetic patients: 79 + 5 vs 72_+ 6, p < 0.02). Renal sodium clearance and distal fractional reabsorption of sodium was unclmnged. Extracellular fluid volume declined by 10% in both groups (p<0.02). Albuminuria and fractional albumin clearance decreased significantly in the nephropathic patients (p < 0.02). Our study suggests that the effects of acetazolamide on kidney function are similar in healthy subjects and patients with diabetic nephropathy.

Renal Handling of Endogenous Lithium in Experimental Diabetes Mellitus in the Rat

“…However its reliability as a marker of proximal tubular function under these pathological conditions has not been evaluated before. Normal parameters of lithium handling may not apply in the diabetic state as administration of acetozolamide in insulin dependent diabetics results in no change in lithium clearance despite the expected inhibition of Na reabsorption (Skott et al 1988). Notwithstanding this, in humans with diabetes mellitus a decrease in fractional Li excretion has been demonstrated, suggesting an increase in proximal tubular Na reabsorption (Hannedouche et al 1990), which is consistent with our micropuncture data.…”

Glomerular Hyperfiltration in Diabetes: Mechanisms, Clinical Significance, and Treatment

“…The carbonic anhydrase inhibitor acetazolamide decreases sodium, chloride, and bicarbonate reabsorption at the level of the proximal tubule. Although acetazolamide is rarely used as a diuretic because its long-term natriuretic effect is modest, 107 several studies have shown that this drug markedly reduces GFR in T1DM with whole-kidney hyperfiltration 108,109 and DKD, 110 likely by TGF activation and independent from sodium balance. 107 Loop diuretics may not affect TGF, because inhibition of the Na-K-2Cl-cotransporter also blocks solute transport into macula densa cells, 107 although discussion is ongoing.…”

Elucidating mechanisms underlying altered renal autoregulation in diabetes

“…Thomson et al (38) demonstrated that a reduced TGF causes glomerular hyperfiltration in STZ-induced diabetes (38). Acetazolamide suppresses diabetic hyperfiltration (25). Paradoxical effects of salt on renal hemodynamics have been reported in diabetes (40).…”