Volume 56, Issue 5, Pages (November 1999)

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Volume 56, Issue 5, Pages 1879-1885 (November 1999) Safety of losartan in hypertensive patients with thiazide-induced hyperuricemia Shahnaz Shahinfar, M.D, Roger L. Simpson, Alexandra D. Carides, Balasamy Thiyagarajan, Yasushi Nakagawa, Jason G. Umans, Joan H. Parks, Fredric L. Coe, for the Losartan Uric Acid Study Group Kidney International Volume 56, Issue 5, Pages 1879-1885 (November 1999) DOI: 10.1046/j.1523-1755.1999.00739.x Copyright © 1999 International Society of Nephrology Terms and Conditions

Figure 1 Study design of this double-blind randomized, parallel, placebo-controlled trial. Timed urine collections for stone profile analysis were done on days 0, 1, 7 and 21 in the clinic. To potentiate the risk of crystal formation, all patients received a high-protein diet (2 g/kg) one day prior to each clinic visit and were placed on a 1500 ml fluid restriction during the visit. Kidney International 1999 56, 1879-1885DOI: (10.1046/j.1523-1755.1999.00739.x) Copyright © 1999 International Society of Nephrology Terms and Conditions

Figure 2 Urine uric acid excretion at times zero, two, four, and six hours on day 1. Changes in urine uric acid were significant for losartan versus placebo (*P < 0.0021) at hours 4 and 6 and for losartan/hydrochlorothiazide (HCTZ) versus HCTZ (+P < 0.0021) at six hours. Symbols are: (▴) losartan, (□) losartan/HCTZ, (○) HCTZ, and (♦) placebo. Bars represent 90% confidence limits. Kidney International 1999 56, 1879-1885DOI: (10.1046/j.1523-1755.1999.00739.x) Copyright © 1999 International Society of Nephrology Terms and Conditions

Figure 3 Serum uric acid at times zero, two, four, and six hours on day 1. No significant changes between groups occurred on day 1. Symbols are: (▴) losartan, (□) losartan/HCTZ, (○) HCTZ, and (♦) placebo. Bars represent 90% confidence limits. Kidney International 1999 56, 1879-1885DOI: (10.1046/j.1523-1755.1999.00739.x) Copyright © 1999 International Society of Nephrology Terms and Conditions

Figure 4 Urine pH at times zero, two, four, and six hours on day 1. Changes in urine pH were significant for losartan versus placebo (*P < 0.0021) at four and six hours. Symbols are: (▴) losartan, (□) losartan/HCTZ, (○) HCTZ, and (♦) placebo. Bars represent 90% confidence limits. Kidney International 1999 56, 1879-1885DOI: (10.1046/j.1523-1755.1999.00739.x) Copyright © 1999 International Society of Nephrology Terms and Conditions

Figure 5 Dihydrogen urate SS (uric acid supersaturation) at times zero, two, four, and six hours on day 1. Decreases in dihydrogen urate SS were significant for losartan versus placebo (*P < 0.0021) at hours 4 and 6. Symbols are: (▴) losartan, (□) losartan/HCTZ, (○) HCTZ, and (♦) placebo. Bars represent 90% confidence limits. Kidney International 1999 56, 1879-1885DOI: (10.1046/j.1523-1755.1999.00739.x) Copyright © 1999 International Society of Nephrology Terms and Conditions

Figure 6 Uric acid excretion rate response to subsequent dosing with losartan. Hours 0 and 4 measurements for each patient are shown. Changes at hour 4 were significant (*P < 0.05, adjusted for placebo) on days 1 and 7 but not on day 21. Symbols are: (▴) losartan and (○) placebo. Kidney International 1999 56, 1879-1885DOI: (10.1046/j.1523-1755.1999.00739.x) Copyright © 1999 International Society of Nephrology Terms and Conditions

Figure 7 Urine pH response to subsequent dosing. Hours 0 and 4 measurements for each subject are shown. Changes at hour 4 were significant (*P < 0.05, adjusted for placebo) on days 1 and 7 but not on day 21. Symbols are (▴) losartan and (○) placebo. Kidney International 1999 56, 1879-1885DOI: (10.1046/j.1523-1755.1999.00739.x) Copyright © 1999 International Society of Nephrology Terms and Conditions

Figure 8 Serum uric acid response to subsequent dosing with losartan. Serum uric acid fell significantly (**P < 0.001) in the losartan group versus placebo by day 7 and remained significantly (*P < 0.05) decreased on day 21. Serum uric also fell significantly (*P < 0.01) in the losartan/HCTZ group versus the HCTZ group but was not significant at day 21. Symbols are: (▴) losartan, (□) losartan/HCTZ, (○) HCTZ, and (♦) placebo. Bars represent 90% confidence limits. Kidney International 1999 56, 1879-1885DOI: (10.1046/j.1523-1755.1999.00739.x) Copyright © 1999 International Society of Nephrology Terms and Conditions