Psychotropic drugs and the kidney

Waller, Derek (1983) Psychotropic drugs and the kidney. University of Southampton, Doctoral Thesis.

Abstract

Studies have been undertaken to determine the prevalence, nature and cause of the renal functional impairment seen during treatment of psychoses with lithium and neuroleptic drugs. In addition, the acute effects of large doses of propranolol and nadolol on renal function have been studied following reports that the former drug may be effective in the treatment of psychotic disorders. A cross-sectional survey of renal function in 101 patients receiving prophylactic lithium treatment demonstrated that glomerular function was not significantly reduced by lithium and that impairment of urine concentrating ability is the major functional defect, occurring in 43% of patients. Reduced maximum urine osmolality was related to both the cumulative dose of lithium and duration of treatment with neuroleptic drugs. There was a correlation between tubular proteinuria and reduced urine concentrating ability which suggests that the relationship between these factors deserves further investigation as a means of predicting nephrotoxicity. In contrast to suggestions by other investigators, urinary excretion of N-acetyl glucosaminidase did not correlate with reduced ability to concentrate urine. A study of the production of cyclic AMP by the renal tubules in a subgroup of patients suggestedthat adenylate cyclase inhibition by lithium may be an important mechanism in the generation of nephrogenic diabetes insipidus. It is probable that this explains the partial reversibility of vasopressin unresponsiveness that has been reported by other investigators on stopping lithium therapy. A study of 26 patients receiving maintenance neuroleptic treatment, who had never been treated with antidepressants or lithium, provided evidence that a reduction in urine concentrating ability may be induced by neuroleptics. Maximum urine osmolality was impaired compared to healthy volunteers, but less than in a group of lithium treated patients of a similar age and sex and matched for duration of neuroleptic use. The reduction in urine concentrating ability during neuroleptic treatment is unlikely to be of clinical significance, except in patients who concurrently or subsequently receive lithium. In the studies of beta-adrenoceptor antagonists in healthy volunteers, propranolol had little effect on renal function at rest. It abolished the rise in renal blood flow and glomerular filtration rate in response to intravenous saline loading without influencing the rate of natriuresis. Nadolol was studied because it has been claimed to increase renal blood flow. However, in the current study it reduced renal blood flow and glomerular filtration rate at rest, and had similar effects to propranolol during salt loading. There was a reduction in sodium excretion after nadolol at rest, and a trend to a reduction after salt loading. The results suggest that nadolol in high doses confers no advantages over propranolol with regard to renal function, and may be detrimental in patients with pre-existing renal impairment or limited cardiac reserve.

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