ATRA therapy restores normal renal function and renal reserve and prevents renal failure

K T Woo, Y K Lau, C M Chan, K S Wong
Annals of the Academy of Medicine, Singapore 2005, 34 (1): 52-9
This article presents clinical data which suggest that the current dosage of losartan 50 to 100 mg/day may not be the optimum in many cases, especially if used as monotherapy in the treatment of proteinuria and we may have to increase to 200 mg/day. However, about 30% of patients cannot take angiotensin-converting enzyme inhibitor (ACEI) because of the side effect of cough. To potentiate the anti-proteinuric effect of losartan, especially for patients who do not adhere to a low salt diet, a 12.5-mg dose of hydro-chlorothiazide may further decrease proteinuria. The main message of this article is that we would have to, in many instances, increase the dose of losartan to a minimum of 100 mg/day or 100 mg twice a day for some patients for optimal therapy. The second message is to monitor the creatinine clearance test (CCT) and to start therapy when CCT is reduced and not wait for serum creatinine to rise to abnormal levels (renal impairment) before starting therapy. The first group involves half a dozen patients with hypertension but no proteinuria. Therapy with losartan is shown to improve the renal function. This data suggest that losartan, apart from its use in reduction of proteinuria, can be used in patients with mild renal impairment without proteinuria to reverse the mild renal impairment and preserve renal function. The second group deals with 3 patients with low creatinine clearance. After a followup period of an average of 3 years, they all developed renal impairment. In another 6 patients, the data suggest that we should perhaps treat patients with low CCT as soon as possible and with dose ranging from 100 to 200 mg/day if necessary, to derive maximum beneficial effect. The third group highlights 5 patients with high CCT due to glomerular hyperfiltration. With time, the high CCT decreases and renal impairment sets in. The data suggest that patients with high CCT should be treated early to prevent renal impairment. The fourth group illustrates 6 patients where their proteinuria was markedly reduced with the increase of losartan from 100 mg/day to 200 mg/day, suggesting that losartan 200 mg/day is probably the optimum dose. In conclusion, apart from its traditional usage in reduction of proteinuria to retard progression to renal failure, the data suggest that losartan is also indicated in patients with renal impairment in the absence of proteinuria; patients with low CCT, patients with high CCT and patients who do not respond to a dosage of 100 mg/day should have the dosage increased to 100 mg twice daily to increase efficacy of losartan. It is hoped that with these new and earlier indications as well as increased dosage of losartan starting with 100 mg, whenever possible, and increasing to 200 mg/day, if there is no response, we can prevent more patients from developing renal failure. Based on these observations, further randomised controlled trials should be designed to address these issues.

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