Serum creatinine elevation after renin-angiotensin system blockade and long term cardiorenal risks: cohort study

Abstract

Objective To examine long term cardiorenal outcomes associated with increased concentrations of creatinine after the start of angiotensin converting enzyme inhibitor/angiotensin receptor blocker treatment. Design Population based cohort study using electronic health records from the Clinical Practice Research Datalink and Hospital Episode Statistics. Setting UK primary care, 1997-2014. Participants Patients starting treatment with angiotensin converting enzyme inhibitors or angiotensin receptor blockers (n=122 363). Main outcome measures Poisson regression was used to compare rates of end stage renal disease, myocardial infarction, heart failure, and death among patients with creatinine increases of 30% or more after starting treatment against those without such increases, and for each 10% increase in creatinine. Analyses were adjusted for age, sex, calendar period, socioeconomic status, lifestyle factors, chronic kidney disease, diabetes, cardiovascular comorbidities, and use of other antihypertensive drugs and non-steroidal anti-inflammatory drugs. Results Among the 2078 (1.7%) patients with creatinine increases of 30% or more, a higher proportion were female, were elderly, had cardiorenal comorbidity, and used non-steroidal anti-inflammatory drugs, loop diuretics, or potassium sparing diuretics. Creatinine increases of 30% or more were associated with an increased adjusted incidence rate ratio for all outcomes, compared with increases of less than 30%: 3.43 (95% confidence interval 2.40 to 4.91) for end stage renal disease, 1.46 (1.16 to 1.84) for myocardial infarction, 1.37 (1.14 to 1.65) for heart failure, and 1.84 (1.65 to 2.05) for death. The detailed categorisation of increases in creatinine concentrations (<10%, 10-19%, 20-29%, 30-39%, and ≥40%) showed a graduated relation for all outcomes (all P values for trends <0.001). Notably, creatinine increases of less than 30% were also associated with increased incidence rate ratios for all outcomes, including death (1.15 (1.09 to 1.22) for increases of 10-19% and 1.35 (1.23 to 1.49) for increases of 20-29%, using <10% as reference). Results were consistent across calendar periods, across subgroups of patients, and among continuing users. Conclusions Increases in creatinine after the start of angiotensin converting enzyme inhibitor/angiotensin receptor blocker treatment were associated with adverse cardiorenal outcomes in a graduated relation, even below the guideline recommended threshold of a 30% increase for stopping treatment.

Late onset renal failure from angiotensin blockade (LORFFAB) and the syndrome of rapid onset endstage renal disease (SORO-ESRD) revisited – Two case reports from Mayo Clinic Health System, Northwestern Wisconsin, USA; a review paper

“…It was indeed our work at the Mayo Clinic Health System in Northwestern Wisconsin that spurred the work of El Nahas and his group from the Sheffield Kidney Institute, Sheffield in the United Kingdom who concluded in 2010 that discontinuation of ACEI/ARB had undoubtedly delayed the onset of RRT in the majority of those studied and that this observation might justify a rethink of our approach to the inhibition of the renin-angiotensin-aldosterone system (RAAS) in patients with advanced CKD who are nearing the start of RRT (11,12). Some other investigators around the world have shown similar reports raising concerns about the potential nephrotoxicity of angiotensin blockade especially in the elderly (>65-year old) with more advanced CKD (13)(14)(15). As a result of these legitimate concerns, we now have a randomized controlled trial to determine whether the pre-emptive withdrawal of ACEI/ARB in patients with advanced CKD would result in improved cardiorenal outcomes -the ongoing STOP ACEi Trial (16,17).…”

Risk factors associated with biochemically detected and hospitalised acute kidney injury in patients prescribed renin angiotensin system inhibitors

“…These changes may not represent “AKI” with any intrinsic renal damage and may simply reflect changes in serum creatinine in the setting of haemodynamic perturbation as glomerular perfusion pressure responds to changes in hydration status. Nevertheless, greater rises in serum creatinine in patients requiring ACEi/ARB therapy highlights a group of patients at greater mortality risk during follow up . Therefore, we would simply state that increased awareness of AKI in patients with HF is required and sensitivity is needed in interpreting AKI alerts in these patients.…”

Блокатори Ренін-Ангіотензинової Системи, Швидкість Клубочкової Фільтрації Й Артеріальний Тиск

“…This tendency was observed even below the guideline recommended threshold of a 30 % increase for treatment discontinuation [6].…”

“…Эта тенденция отмечалась в значениях ниже рекомендо-ванного ориентиром порога увеличения на 30 % для прекращения лечения блокаторами РАС [6].…”