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Renal actions of calcium channel antagonists
H Osswald1, G Weinheimer, J F Kapp
1Gödecke Research Institute, Freiburg, Federal Republic of Germany.
Abstract:
The actions of L-channel calcium antagonists on the kidney are the result of direct and indirect effects. The direct effects are characterized by vasodilation, especially when the renal vascular resistance was enhanced beforehand. The increase in glomerular filtration rate is small and transient in most of the clinical trials with chronic administration. An important direct effect of calcium channel antagonists on renal function is the increase of sodium and water excretion by a tubular action that occurs in the absence of hemodynamic changes. The mechanism of the tubular effects of calcium channel antagonists is not understood at present. An indirect effect of calcium channel antagonists on the kidney is the inhibition of the aldosterone secretion by the adrenals. A sodium and water loss due to inhibition of tubular reabsorption leads to an increase in renin activity and aldosterone concentration in the plasma as seen typically with diuretics. The dissociation of renin- and aldosterone increase by calcium channel antagonists is a new finding and contributes favorably to the anti-hypertensive efficacy of calcium channel antagonists. In experimental acute renal failure mainly diltiazem and verapamil improved recovery of kidney function. In kidney transplantation, diltiazem reduced posttransplant acute tubular necrosis and improved primary graft function. It remains to be seen whether other calcium channel antagonists have a similar beneficial therapeutic effect in pathological states of renal function.
Insights
Calcium channel blockers offer direct kidney benefits like increased sodium/water excretion and indirect effects by inhibiting aldosterone. These actions improve kidney function and hypertension management.
Area of Science:
- Nephrology
- Pharmacology
Background:
- L-channel calcium antagonists exert direct and indirect effects on renal function.
- Their direct actions include renal vasodilation and increased sodium/water excretion via tubular mechanisms.
- Indirect effects involve aldosterone secretion inhibition, impacting renin-angiotensin-aldosterone system dynamics.
Purpose of the Study:
- To elucidate the multifaceted actions of L-channel calcium antagonists on kidney physiology and pathology.
- To investigate the therapeutic potential of these agents in acute renal failure and kidney transplantation.
Main Methods:
- Review of clinical trials and experimental studies on calcium channel antagonists' renal effects.
- Analysis of direct tubular actions and indirect hormonal modulations.
- Evaluation of outcomes in acute renal failure models and post-transplant scenarios.
Main Results:
- Direct effects: renal vasodilation (especially with pre-existing resistance), transient GFR increase, and significant tubular sodium/water excretion.
- Indirect effects: inhibition of aldosterone secretion, leading to a dissociation between renin and aldosterone levels, enhancing antihypertensive efficacy.
- Experimental evidence shows diltiazem and verapamil improve recovery in acute renal failure; diltiazem reduces post-transplant ATN and improves graft function.
Conclusions:
- L-channel calcium antagonists possess beneficial direct and indirect renal effects.
- Their tubular actions and modulation of the renin-aldosterone system contribute to antihypertensive efficacy.
- Diltiazem demonstrates protective effects in acute renal failure and kidney transplantation, warranting further investigation for other agents.