All concepts, explanations, trials, and studies have been re-written in plain English and may contain errors. I am not a doctor ----------------------------------------------------------- KIDNEY FAILURE AND ARBS ----------------------- INTRODUCTION Diabetic nephropathy is the leading cause of end-stage kidney disease. Interruption of the RAS (renin-angiotensin system) slows the worsening of kidney disease in patients with type one diabetes but we don't know about patients with type 2, which is more common. We studied the role of the ARB (see http://www.jonsplace.org/CHFace.htm) losartan (Cozaar) in patients with type 2 diabetes and kidney failure. METHODS 1,513 patients participated. This was a randomized, double-blind study comparing 50mg to 100mg losartan daily versus placebo. Patients kept taking their usual meds (mostly diuretics, calcium channel blockers, nitro, and beta-blockers). Follow-up was an average of 3.4 years. Primary end point was doubling of starting blood creatinine level, end-stage kidney disease, or death. Secondary end points were heart-related complications and mortality; proteinuria; and how fast kidney disease got worse. RESULTS 327 patients in the losartan group suffered the primary end point, compared to 359 in the placebo group. Losartan reduced risk of doubling blood creatinine level and end-stage kidney disease, but did not affect risk of death. Heart-related complications and death risk was similar in the 2 groups. Risk of first hospitalization for heart failure was lower with losartan. Level of proteinuria went down 35% with losartan compared to placebo. CONCLUSIONS Losartan gave kidney benefits in patients with type 2 diabetes and nephropathy, and it was generally well tolerated. Title: Effects of losartan on renal and cardiovascular outcomes in patients with type 2 diabetes and nephropathy. Authors: Brenner BM, Cooper ME, de Zeeuw D, Keane WF, Mitch WE, Parving HH, Remuzzi G, Snapinn SM, Zhang Z, Shahinfar S; RENAAL Study Investigators. [bbrenner@partners.org] Source: N Engl J Med 2001 Sep 20;345(12):861-9 Comment in: N Engl J Med. 2001 Sep 20;345(12):910-2 PMID: 11565518 ============================================================ ACE inhibitors and ARBs increase kidney blood flow, but glomerular filtration rate does not change. Both drugs reduce arterial blood pressure, glomerular capillary pressure and proteinuria. This probably protects the kidneys. Studies show that the kidney protecting effects of ACE inhibitors and ARBs come from inhibiting angiotensin II and not from inhibiting bradykinin degradation. Several studies suggest other kidney protective effects of ACE inhibitors and ARBs. However, controlled clinical studies are lacking. Experimental data suggest that taking both drugs may better reduce inflammatory cell movement into the kidney. Long-term clinical trials using ARBs are needed before these drugs can be recommended as strongly as ACE inhibitors. Title: Angiotensin II type-1-receptor antagonists from the viewpoint of nephrology. Authors: Hauser AC, Horl WH. Source: Wien Med Wochenschr 2001;151(7-8):160-4 PMID: 11450164 ============================================================ INTRODUCTION Blood pressure reduction is the most significant factor in delaying onset and worsening of kidney disease. Blocking the RAS (renin-angiotensin system) using ACE inhibitors slows the worsening of kidney disease. More recently, ARBs have been used to further protect the kidneys. Trials with a variety of ARBs have clearly shown their anti-proteinuric effectiveness in kidney disease patients. The effects of ARBs are similar to those of ACE inhibitors. Ongoing long-term clinical trials will show whether ARBs also preserve kidney function. The role of ARBs in high blood pressure patients with type 2 diabetes is being studied in 3 large trials: 1) Appropriate Blood Pressure Control in Diabetes-Part 2 With Valsartan 2) Losartan Renal Protection Study 3) Irbesartan Diabetic Nephropathy Trial Definite evidence of the long-term protective effects of ARBs in chronic kidney disease is expected from these studies. Title: Angiotensin II subtype 1 receptor blockers and renal function. Author: Toto R. [robert.toto@utsouthwestern.edu] Source: Arch Intern Med 2001 Jun 25;161(12):1492-9 PMID: 11427096 ========================================================= INTRODUCTION Prolonged ACE inhibitor therapy leads to angiotensin I accumulation which may "escape" ACE inhibition, harming patients with chronic kidney disease. We studied whether losartan added to maximum ACE inhibitor therapy (40mg lisinopril daily) blocked more angiotensin II in patients with chronic kidney failure with high blood pressure. METHODS 16 patients with chronic kidney failure completed a crossover, randomized, controlled trial. Each period was one month with a 2 week washout between periods. 12 patients had diabetic nephropathy, and 4 had chronic glomerulonephritis. The average patient age was 53 years. In one period, patients took 40mg lisinopril daily along with their other blood pressure meds. In the other period, they took 50mg losartan daily in addition to their other blood pressure meds. We measured walking blood pressure, kidney function (glomerular filtration rate), and heart output. Resting blood renin activity, blood aldosterone and urine protein were also measured in all patients. RESULTS Seated blood pressure was 156/88 mm Hg. Pulse rate was 77. Cardiac index was 2.9 L/min/m(2). Average 24-hour protein excretion/g creatinine did not change. Average amount of change in protein excretion that was due to losartan was +1%. Change in systolic walking blood pressure due to losartan was 4.6 mm Hg, and change in diastolic was 1.5 mm Hg. No change was seen in heart output. However, there was an average 14% increase in glomular filtration rate due to losartan. A fall in blood renin activity of 32% was also seen. No electrolyte problems were seen. CONCLUSIONS Add-on losartan therapy did not improve proteinuria or walking blood pressure over one month. However, improvement of glomular filtration rate and fall in blood renin level show an effect. Deciding whether add-on ARBs substantially help kidney failure patients needs larger and longer prospective, randomized controlled trials. Title: Add-on angiotensin receptor blockade with maximized ACE inhibition. Author: Agarwal R. [ragarwal@iupui.edu] Source: Kidney Int 2001 Jun;59(6):2282-9 PMID: 11380832 ========================================================= INTRODUCTION We studied the effect of losartan on kidney function in non-diabetic patients with chronic kidney failure. This was an open, prospective, follow-up study of one year. METHODS 29 high blood pressure patients (14 females and 15 males with an average age of 63 years) with non-diabetic chronic kidney failure of several causes participated. They took 50mg losartan daily plus any other drugs they needed. Follow up was 13 months. 18 patients were taking ACE inhibitors plus other high blood pressure drugs at study start. Patients had been followed for almost 4 years previously. Worsening of kidney failure was measured as the slope of the reciprocal of blood creatinine level versus time in months. RESULTS Study start After one year with losartan Blood pressure 149/90 mmHg 142/84 mmHg Creatinine clearance 29 ml/min 29 ml/min Urine protein excretion 1.7 g/24 h 1.2 g/24 h Blood creatinine 3.18 mg ml 3.49 mg ml Disease progression -0.0039 mg/month -0.0012 mg/month CONCLUSIONS The rate of progression of kidney function in patients with non-diabetic chronic kidney failure is slowed down after a year of treatment with losartan. The results of this preliminary study suggest that ARBs offer kidney protection in this subset of patients. These results need to be confirmed in controlled trials. Title: Effect of angiotensin II receptor blockade on renal disease progression in patients with non-diabetic chronic renal failure. Authors: Mora-Macia J, Cases A, Calero F, Barcelo P. Source: Nephrol Dial Transplant 2001;16 Suppl 1:82-4 PMID: 11369829