Interruption of the renin-angiotensin system in hypertensive patients by captopril induces sustained reduction in aldosterone secretion, potassium retention and natriuresis. liter, multiply by 1.0), or a clinical center initiated hyperkalemia stop point. Results A total of 6497 potassium measurements were obtained, and 80 events in 51 subjects were recognized (76 events driven by a central laboratory result and 4 driven by a clinical centerCinitiated hyperkalemia quit point). Compared with a GFR higher than 50 mL/min/1.73 m2, after multivariable adjustment, the hazard ratio (HR) for hyperkalemia in patients with a GFR between 31 and 40 mL/min/1.73 m2 and a GFR lower than 30 mL/min/1.73 m2 was 3.61 (95% confidence interval [CI], 1.42C9.18 [values .05 were considered statistically significant, without adjustment for multiple comparisons. RESULTS The baseline characteristics are offered in Table 1. Subjects were predominantly male and on average middle-aged and obese. There was a wide range of systolic BP with a mean of 150.0 mm Hg. The mean GFR was 46.6 mL/min/1.73 m2, corresponding to stage 3 chronic kidney disease. The mean (SD) number of potassium measurements was 6.2 (2.6) per patient over a mean follow-up period of 3.0 years. Of the 6497 available pre-ESRD potassium measurements obtained, only 76 met criteria for hyperkalemia (1.2%). After accounting for 4 hyperkalemia stop points triggered by a decision at the local center, 76 events driven by a result at the central laboratory were identified, for a total of 80 hyperkalemic events in 51 patients (Table 2). As given in Table 2, 11.2% of patients with a baseline GFR of 40 mL/min/1.73 m2 or lower experienced a hyperkalemic event, whereas less than 1.6% of patients with a GFR higher than 40 mL/min/1.73 m2 had a hyperkalemic event. As given in Table 3, the relatively higher rate of hyperkalemia in those with GFR of 40 mL/min/1.73 m2 or lower persisted in the multivariable analysis, which included adjustment for randomized drug assignment, age at randomization, sex, baseline NSAID use, baseline BMI, baseline UP/Cr, baseline glucose level, and baseline potassium level. There was no significant difference in the rate of hyperkalemia in those with a GFR between 40 and 50 mL/min/1.73 m2 vs a GFR higher than 50 mL/min/1.73 m2. Table 1 Baseline Demographic Characteristicsa ValueValueValueValueValueWeinberg, Appel, Bakris, Gassman, Thornley-Brown, and Phillips. Appel, Bakris, Gassman, Wang, Lewis, Pogue, Thornley-Brown, and Phillips. Weinberg, Appel, Gassman, Greene, Kendrick, Wang, Lash, Lewis, Pogue, Thornley-Brown, and Phillips. Weinberg, Kendrick, Wang, and Phillips. Critical revision of the manuscript for important intellectual content: Weinberg, Appel, Bakris, Gassman, Greene, Kendrick, Lash, Lewis, Pogue, and Metformin HCl Thornley-Brown. Gassman, Greene, Kendrick, Wang, and Phillips. Appel, Bakris, Lash, and Phillips. Weinberg, Appel, Gassman, Pogue, and Phillips. Appel, Lewis, Pogue, and Phillips. Financial Disclosure: None reported. Previous Presentation: This study was presented as a poster at the American Heart Association’s 63rd High Blood Pressure Research Conference; September 23, 2009; Chicago, Illinois. REFERENCES 1. The GISEN Group (Gruppo Italiano di Studi Epidemiologici in Nefrologia) Randomised placebo-controlled trial of effect of ramipril on decline in glomerular filtration rate and risk of terminal renal failure in proteinuric, non-diabetic nephropathy. Lancet. 1997;349(9069):1857C1863. [PubMed] [Google Scholar] 2. Jafar TH, Schmid CH, Landa M, et al. Angiotensin-converting enzyme inhibitors and progression of nondiabetic renal disease: a meta-analysis of patient-level data. Ann Intern Med. 2001;135(2):73C87. [PubMed] [Google Scholar] 3. Ruggenenti P, Perna A, Gherardi G, Gaspari Metformin HCl F, Benini R, Remuzzi G. Renal function and requirement for dialysis in chronic nephropathy patients on long-term ramipril: REIN follow-up trial: Gruppo Italiano di Studi Epidemiologici in Nefrologia (GISEN): Ramipril Efficacy in Nephropathy. Lancet. 1998;352(9136):1252C1256. Metformin HCl [PubMed] [Google Scholar] 4. Hou FF, Zhang X, Zhang GH, et al. Efficacy and safety of benazepril for advanced chronic renal insufficiency. N Engl J Med. 2006;354(2):131C140. [PubMed] [Google Scholar] 5. Atlas SA, Case DB, Sealey JE, Laragh JH, McKinstry DN. Interruption of the renin-angiotensin system in hypertensive patients by captopril induces sustained reduction in aldosterone secretion, potassium retention and natriuresis. Hypertension. 1979;1(3):274C280. [PubMed] [Google Scholar] 6. Reardon LC, Macpherson DS. Hyperkalemia in outpatients using angiotensin-converting enzyme inhibitors: how much should we worry? Arch Intern Med. 1998;158(1):26C32. [PubMed] [Google Scholar] 7. Hannedouche.As given in Table 2, 11.2% of patients with a baseline GFR of 40 mL/min/1.73 m2 or lower experienced a hyperkalemic event, whereas less than 1.6% of patients with a GFR higher than 40 mL/min/1.73 m2 had a hyperkalemic event. m2, after multivariable adjustment, the hazard ratio (HR) for hyperkalemia in patients with a GFR between 31 and 40 mL/min/1.73 m2 and a GFR lower than 30 mL/min/1.73 m2 was 3.61 (95% confidence interval [CI], 1.42C9.18 [values .05 were considered statistically significant, without adjustment for multiple comparisons. RESULTS The baseline characteristics are presented in Table 1. Subjects were predominantly male and on average middle-aged and obese. There was a wide range of systolic BP with a mean of 150.0 mm Hg. The mean GFR was 46.6 mL/min/1.73 m2, corresponding to stage 3 chronic kidney disease. The mean (SD) number of potassium measurements was 6.2 (2.6) per patient over a mean follow-up period of 3.0 years. Of the 6497 available pre-ESRD potassium measurements obtained, only 76 met criteria for hyperkalemia (1.2%). After accounting for 4 hyperkalemia stop points triggered by a decision at the local center, 76 events driven by a result at the central laboratory were identified, for a total of Cspg2 80 hyperkalemic events in 51 patients (Table 2). As given in Table 2, 11.2% of patients with a baseline GFR of 40 mL/min/1.73 m2 or lower experienced a hyperkalemic event, whereas less than 1.6% of patients with a GFR higher than 40 mL/min/1.73 m2 had a hyperkalemic event. As given in Table 3, the relatively higher rate of hyperkalemia in those with GFR of 40 mL/min/1.73 m2 or lower persisted in the multivariable analysis, which included adjustment for randomized drug assignment, age at randomization, sex, baseline NSAID use, baseline BMI, baseline UP/Cr, baseline glucose level, and baseline potassium level. There was no significant difference in the rate of hyperkalemia in those with a GFR between 40 and 50 mL/min/1.73 m2 vs a GFR higher than 50 mL/min/1.73 m2. Table 1 Baseline Demographic Characteristicsa ValueValueValueValueValueWeinberg, Appel, Bakris, Gassman, Thornley-Brown, and Phillips. Appel, Bakris, Gassman, Wang, Lewis, Pogue, Thornley-Brown, and Phillips. Weinberg, Appel, Gassman, Greene, Kendrick, Wang, Lash, Lewis, Pogue, Thornley-Brown, and Phillips. Weinberg, Kendrick, Wang, and Phillips. Critical revision of the manuscript for important intellectual content: Weinberg, Appel, Bakris, Gassman, Greene, Kendrick, Lash, Lewis, Pogue, and Thornley-Brown. Gassman, Greene, Kendrick, Wang, and Phillips. Appel, Bakris, Lash, and Phillips. Weinberg, Appel, Gassman, Pogue, and Phillips. Appel, Lewis, Pogue, and Phillips. Financial Disclosure: None reported. Previous Presentation: This study was presented as a poster at the American Heart Association’s 63rd High Blood Pressure Research Conference; September 23, 2009; Chicago, Illinois. REFERENCES 1. The GISEN Group (Gruppo Italiano di Studi Epidemiologici in Nefrologia) Randomised placebo-controlled trial of effect of ramipril on decline in glomerular filtration rate and risk of terminal renal failure in proteinuric, non-diabetic nephropathy. Lancet. 1997;349(9069):1857C1863. [PubMed] [Google Scholar] 2. Jafar TH, Schmid CH, Landa M, et al. Angiotensin-converting enzyme inhibitors and progression of nondiabetic renal disease: a meta-analysis of patient-level data. Ann Intern Med. 2001;135(2):73C87. [PubMed] [Google Scholar] 3. Ruggenenti P, Perna A, Gherardi G, Gaspari F, Benini R, Remuzzi G. Renal function and requirement for dialysis in chronic nephropathy patients on long-term ramipril: REIN follow-up trial: Gruppo Italiano di Studi Epidemiologici in Nefrologia (GISEN): Ramipril Efficacy in Nephropathy. Lancet. 1998;352(9136):1252C1256. [PubMed] [Google Scholar] 4. Hou FF, Zhang X, Zhang GH, et al. Efficacy and safety of benazepril for advanced chronic renal insufficiency. N Engl J Med. 2006;354(2):131C140. [PubMed] [Google Scholar] 5. Atlas SA, Case DB, Sealey JE, Laragh JH, McKinstry DN. Interruption of the renin-angiotensin system in hypertensive patients by captopril induces sustained reduction in aldosterone secretion, potassium retention and natriuresis. Hypertension. 1979;1(3):274C280. [PubMed] [Google Scholar] 6. Reardon LC, Macpherson DS. Hyperkalemia in.