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Streptozotocin-induced renal hemodynamic changes in isogenic Lewis rats: a kidney transplant study
P Churchill1, M Churchill, A Bidani
1Department of Physiology, Wayne State University School of Medicine, Detroit, Michigan 48201.
Abstract:
Streptozotocin (STZ)-induced diabetes mellitus is associated with decreased renal clearances of inulin and p-aminohippurate (PAH). The present experiments were designed to determine whether STZ-induced renal hemodynamic changes are due to the drug per se, rather than to the diabetic state that it induces. Isogenic Lewis rats with native right and transplanted left kidneys were studied. In one group, kidney donors received 50 mg STZ/kg body wt on day 1 and transplantation was performed on day 4 (untreated recipients). On day 29, the inulin and PAH clearances of these nondiabetic recipients were, respectively, 0.94 +/- 0.04 and 2.58 +/- 0.11 ml.min-1 x g-1 for the transplanted left kidney (previously exposed to STZ) and 0.95 +/- 0.07 and 2.54 +/- 0.14 ml.min-1 x g-1 for the native right kidney (never exposed to STZ). In another group, recipients received STZ on day 1 and transplantation was performed on day 4 (untreated donors). On day 29, the inulin and PAH clearances of these diabetic recipients were, respectively, 0.62 +/- 0.04 and 1.46 +/- 0.11 ml.min-1 x g-1 for the transplanted left kidney (never exposed to STZ) and 0.61 +/- 0.05 and 1.42 +/- 0.08 ml.min-1 x g-1 for the native right kidney (previously exposed to STZ). We conclude that the diabetic state, rather than STZ, is responsible for the decreased renal clearances of inulin and PAH in this experimental model.
Insights
The diabetic state, not the drug streptozotocin (STZ), causes reduced kidney function in rats. This study clarifies that diabetes mellitus, not STZ itself, impairs renal clearances of inulin and p-aminohippurate (PAH).
Area of Science:
- Nephrology
- Endocrinology
- Pharmacology
Background:
- Streptozotocin (STZ) is widely used to induce diabetes mellitus in experimental models.
- STZ-induced diabetes is associated with impaired renal function, specifically reduced clearances of inulin and p-aminohippurate (PAH).
- The precise cause of these renal hemodynamic changes—the drug itself or the resulting diabetic state—remains unclear.
Purpose of the Study:
- To differentiate the effects of streptozotocin (STZ) per se from the effects of the induced diabetic state on renal hemodynamics.
- To investigate whether STZ directly impacts kidney function or if the observed changes are secondary to hyperglycemia and metabolic alterations.
Main Methods:
- Utilized isogenic Lewis rats with native and transplanted kidneys to isolate the effects of STZ exposure.
- Administered STZ to kidney donors or recipients before transplantation to create distinct experimental groups: STZ-exposed kidneys in non-diabetic recipients and non-exposed kidneys in diabetic recipients.
- Measured renal clearances of inulin and p-aminohippurate (PAH) in both native and transplanted kidneys 29 days post-transplantation.
Main Results:
- Nondiabetic recipients with STZ-exposed transplanted kidneys showed normal inulin and PAH clearances, similar to their native kidneys.
- Diabetic recipients, regardless of whether their native or transplanted kidneys were exposed to STZ, exhibited significantly reduced inulin and PAH clearances.
- Renal clearances in diabetic recipients were consistently lower for both native and transplanted kidneys, indicating a systemic effect of diabetes.
Conclusions:
- The diabetic state, induced by streptozotocin (STZ), is the primary cause of decreased renal clearances of inulin and p-aminohippurate (PAH).
- Streptozotocin itself does not appear to directly cause the observed renal hemodynamic impairment; rather, the metabolic consequences of diabetes are responsible.
- These findings are crucial for understanding the pathophysiology of diabetic nephropathy and interpreting results from STZ-induced diabetes models.