Renin–angiotensin system inhibition in advanced chronic kidney disease (original) (raw)
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Retarding the progression of chronic kidney disease with renin angiotensin system blockade
Indian Journal of Nephrology, 2012
We assessed the effect of renin angiotensin system blockade (RASB) in chronic kidney disease (CKD) of diverse etiology. Two hundred and sixty-five consecutive CKD patients attending our renal clinic, with estimated glomerular filtration rate (eGFR) of 20-70 ml/min/1.73m 2 at baseline and a minimal follow-up of 1 year, were studied retrospectively. We devised a scoring system to quantify RASB, wherein the maximum dose of an agent recommended for control of hypertension was scored as 1. The renal endpoints studied were the rate of change in eGFR (∆eGFR) and decline of eGFR>50%. The mean age was 48 ± 11.2 years and 69% were male. The mean duration of follow-up was 4 ± 2.7 years. The rate of ∆eGFR was −1.5 ± 5.0 ml/min/1.73 m 2 per year in patients who received RASB (N=168) and −6.0 ± 5.4 in those who did not (N=97) (P<0.001). The incidence of decline of eGFR >50% was 11.3% with RASB and 24.7% without (P=0.003). In a subgroup of patients who received RASB, the incidence of decline of eGFR >50% was 17.8% in the low-dose RASB group (N=84, RASB score 0.63 ± 0.38) and 4.8% in the high-dose group (N=84, RASB score 2.5 ± 0.7) (P=0.001). RASB was associated with significantly better renoprotection in CKD of diverse etiology, even in nonproteinuric diseases. This effect appeared to be dose-dependent, with higher supramaximal doses exhibiting better renoprotection than the lower conventional doses. Our results make a strong case for use of aggressive RASB in all CKD patients to postpone end-stage renal disease.
Nefrología (English Edition), 2020
Introduction: The renoprotective effect of renin-angiotensin (RAS) blockers (angiotensin converting enzyme inhibitors and angiotensin receptor blockers) has been questioned in patients with advanced chronic kidney disease (CKD). Moreover, combination therapy (dual RAS blockade) can further accelerate renal function decline in some populations at risk. However, it is unknown whether this adverse outcome is due to a dose-dependent effect or if it can be attributed more specifically to a drug interaction. Aim: This study aims to investigate if the rate of renal function decline in advanced CKD patients is associated to the doses of RAS blockers, and if dual RAS blockade worsens renal function independently of major confounding factors. Material and methods: Retrospective, observational study in an incident cohort of adult patients with CKD stage 4 or 5 not on dialysis, treated with RAS blockers for at least 6 months prior to the study inclusion. Inclusion criteria were: having at least three consecutive measurements of estimated glomerular filtration rate (eGFR) in a follow-up period >3 months. Decline in renal function was estimated as the slope of the individual linear regression line of eGFR over follow-up time. Equipotent doses of RAS blockers were normalised for a body weight of 70 kg or a body surface area of 1.73 m 2 (END-RASI). Associations of END-RASI or dual RAS blockade with the rate of renal function decline were analysed by uni-or multivariate linear regression models, accounting for major confounding variables. Results: The study group consisted of 813 patients (mean age 64 ± 14 years, 430 males) with a mean eGFR 14.9 ± 4.2 ml/min/1.73 m 2. 729 patients were on RAS blockade monotherapy and 84 on dual RAS blockade. Median END-RASI in the whole group was 0.91 (I.Q. ranges 0.69-1.20). Patients on dual RAS blockade had significantly higher END-RASI than the rest of study patients (1.52 ± 0.49 vs. 0.93 ± 0.44; p < 0.0001).
Is there added value to adding ARB to ACE inhibitors in the management of CKD?
Journal of the American Society of …, 2009
Antagonism of the rennin-angiotensin-aldosterone-system (RAAS) decreases BP and reduces proteinuria in chronic kidney disease. BP is decreased approximately 5 mmHg when angiotensin II blockers are added to angiotensin-converting enzyme (ACE) inhibitors and is less than typically seen when other agents are added to existing ACE inhibitor regimens. Dual RAAS blockade results in additional reduction in proteinuria. Clinically insignificant increases in hyperkalemia and modest decreases in GFR occur. Data regarding long-term preservation of renal function are lacking. We suggest dual RAAS blockade be used in patients with chronic kidney disease with residual proteinuria on maximal ACE inhibitor or angiotensin II blocker therapy, anticipating additional data with ongoing trials.
The Journal of Clinical Hypertension
Renin-angiotensin-aldosterone system inhibitors (RAASi) are recommended for chronic kidney disease (CKD) patients. In this study, we describe RAASi prescription patterns in the Chronic Kidney Disease Outcomes and Practice Patterns Study (CKDopps) in Brazil, Germany, France, and the United States (US). 5870 patients (mean age 66-72 years; congestive heart failure [CHF] in 11%-19%; diabetes in 43%-54%; serum potassium ≥5 in 20%-35%) were included. RAASi prescription was more common in Germany (80%) and France (77%) than Brazil (66%) and the United States (52%), where the prevalence of prescription decreases particularly in patients with CKD stage 5. In the multivariable regression model, RAASi prescription was least common in the United States and more common in patients who were younger, had
Late-onset renal failure from angiotensin blockade (LORFFAB) in 100 CKD patients
2008
Introduction Notwithstanding proven renoprotection from RAAS blockade (AB) with ACE inhibitors and ARBs, and despite increasing utilization of AB in the US, we have continued to experience a CKD/ESRD epidemic. Given concerns for iatrogenic CKD/ESRD, we designed a prospective study to analyze the course of eGFR following withdrawal of AB in such patients. Patients Between September 2002 and February 2005, all consecutive CKD patients on AB presenting with [25% increase in baseline serum creatinine were enrolled. eGFR following withdrawal of AB was monitored. The main outcome measures were serum creatinine, MDRD eGFR, and UA/Cr. Results 100 Caucasians, M:F = 52:48, mean age 71.5 years were enrolled. Mean follow up was 26 months. Sixteen patients progressed to ESRD, of whom seven died. In 74, eGFR improved from 23.9 ± 9 (7-47) to 39.2 ± 15.4 (17-89) ml/min/ 1.73 m 2 BSA, 26.5 (3-46) months after stopping AB (P = 0.001). The majority of the cohort, 95 patients, had known risk factors: 26 with RAS, 12 hypovolemia, 11 sepsis, 10 NSAIDs/cox II inhibtor use/ abuse, 7 CIN, 2 congestive heart failure, 2 obstructive uropathy, and 27 with other medical and surgical causes, including malignancies, postoperative states, and infections. In the 26 with RAS, 5 with higher baseline creatinine-2.1 ± 0.6 versus 1.5 ± 0.4 mg/ dL, P = 0.013, progressed to ESRD; 4/5 ESRD patients died after 6.3 months. The remaining five patients (one male and four females), mean age 68 (44-83) years, demonstrated sustained improved eGFR with discontinuation (four) or reduction (one) of RAAS blockade, despite normal renal arteries and the absence of known traditional risk factors. UA/Cr generally increased following withdrawal of AB. Conclusions Worsening azotemia in older susceptible CKD patients on AB, often but not always associated with known precipitating risk factors, remains under-recognized. Sustained improved eGFR often follows the discontinuation of AB. The practising physician should be well aware of these syndromes. Our observations call for further study. No external funding was involved in this study. Institutional review board (IRB) approval was obtained. This work is dedicated to the memory of a pleasant unnamed 74-year-old white woman, with ESRD, who died suddenly at home watching television, probably from a malignant arrhythmia.
Targeting the Renin Angiotensin System in Dialysis Patients
Seminars in Dialysis, 2011
Patients on chronic dialysis therapy have a dramatic excess cardiovascular risk compared to any other population, including those with overt diabetic nephropathy. Despite this, patients on dialysis are almost invariably excluded from trials evaluating the cardioprotective effect of novel treatments. Consistent evidence is available that inhibitors of the renin-angiotensin system, such as angiotensin-converting enzyme (ACE) inhibitors or angiotensin II receptor blockers (ARBs), are more cardioprotective than other antihypertensive agents in patients with chronic renal disease or diabetes (with or without renal involvement), but whether this applies also to patients on dialysis is unknown. However, clear evidence is available that ACE inhibitors and ARBs reduce morbidity and mortality in patients on dialysis with heart failure (HF) or atrial fibrillation (AF). Moreover, these drugs may preserve residual renal function in those with preterminal kidney failure as well as vascular access and peritoneal membrane function in those on extracorporeal or peritoneal dialysis, respectively. These drugs also show an excellent tolerability profile in this population. Thus, ACE inhibitors and ARBs are indicated in patients on dialysis with HF or AF. Available evidence suggests that they should be first-choice therapy in patients on dialysis with hypertension, though trials are still needed to formally demonstrate their superior cardioprotective effect over other antihypertensives in this population.
JAMA internal medicine, 2014
The benefit of using a renin-angiotensin-aldosterone system blocker such as an angiotensin-converting enzyme inhibitor (ACEI) or an angiotensin II receptor blocker (ARB) for patients with advanced chronic kidney disease (CKD) remains undetermined. To assess the effectiveness and safety of ACEI/ARB use for advanced predialysis CKD in patients with hypertension and anemia. DESIGN Prospective cohort study. Taiwan. From January 1, 2000, through June 30, 2009, we selected 28 497 hypertensive adult patients with CKD. Serum creatinine levels were greater than 6 mg/dL, hematocrit levels were less than 28%, and patients were treated with erythropoiesis-stimulating agents. Users (n = 14,117) and nonusers (n = 14,380) of ACEIs/ARBs. We used Cox proportional hazards regression models to estimate hazard ratios (HRs) for commencement of long-term dialysis and all-cause mortality for ACRI/ARB users vs nonusers. In a median follow-up of 7 months, 20,152 patients (70.7%) required long-term dialysis ...