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Verapamil limits shockwave-induced renal tubular damage in vivo
W L Strohmaier1, A Abelius, I Billes
1Department of Urology, Eberhard Karls University, Tübingen, Germany.
Abstract:
Previous investigations on Madin Darby Canine Kidney (MDCK) cells demonstrated the protective effect of verapamil against shockwave-induced tubular dysfunction. In the present study, we investigated whether verapamil is also protective against shockwave-induced damage in vivo. Male rates were randomly assigned to three groups: verapamil (N = 18) (Group I), control (N = 18) (Group II), or sham treatment (N = 4) (Group III). Groups I and II were treated with 500 shockwaves to each kidney with the Dornier MFL 5000 at 18 kV. Animals assigned to Group III received only anesthesics. Verapamil was given to the animals in Group I for 5 days starting 1 day before shockwave exposure. Urine was collected for 8 hours the day before and immediately, 1.7, and 28 days after shockwave exposure (SWE) for measurement of volume, osmolality, hemoglobin, protein, N-acetyl-beta-glucosaminidase (NAG), beta 2-microglobulin (beta 2M), sodium, and creatinine. Kidneys were perfused and removed for histologic study 1, 7, and 28 days after SWE in six animals of Groups I and II. Blood was taken in these rats (Day 1 after SWE) for the determination of creatinine and sodium and the calculation of the creatinine clearance (CCr) and the fractional excretion of sodium (FENa). After SWE, there was strong diuresis and significantly increased excretion of NAG and beta 2M in the controls, while urine osmolality decreased. These changes were significantly less pronounced in the verapamil-treated rats. The CCr was higher and FENa lower than in the latter group.(ABSTRACT TRUNCATED AT 250 WORDS)
Insights
Verapamil protects kidneys from shockwave-induced damage in rats. Treatment reduced kidney dysfunction markers and improved kidney function after shockwave exposure, indicating a protective effect in vivo.
Area of Science:
- Nephrology
- Pharmacology
- Biomedical Engineering
Background:
- Previous studies showed verapamil protects Madin Darby Canine Kidney (MDCK) cells from shockwave injury.
- The in vivo protective effects of verapamil against shockwave-induced kidney damage remain to be fully elucidated.
Purpose of the Study:
- To investigate the in vivo protective effects of verapamil against shockwave-induced kidney damage in a rat model.
- To assess the impact of verapamil on renal function and tubular injury markers following shockwave exposure.
Main Methods:
- Male rats were divided into verapamil, control, and sham groups.
- Verapamil or placebo was administered for 5 days, with shockwave exposure (500 waves at 18 kV) to both kidneys in verapamil and control groups.
- Urine and blood samples were collected at various time points for analysis of volume, osmolality, hemoglobin, protein, N-acetyl-beta-glucosaminidase (NAG), beta 2-microglobulin (beta 2M), creatinine, and sodium.
Main Results:
- Shockwave exposure in control rats led to significant diuresis, increased NAG and beta 2M excretion, and decreased urine osmolality.
- These adverse effects were significantly attenuated in the verapamil-treated group.
- Verapamil treatment resulted in higher creatinine clearance (CCr) and lower fractional excretion of sodium (FENa) compared to controls.
Conclusions:
- Verapamil demonstrates a protective effect against in vivo shockwave-induced kidney damage in rats.
- The drug mitigates tubular dysfunction and preserves renal function following shockwave exposure.
- Verapamil represents a potential therapeutic agent for preventing or reducing kidney injury from shockwave lithotripsy.