Should We STOP Angiotensin Converting Enzyme Inhibitors/Angiotensin Receptor Blockers in Advanced Kidney Disease?

Ahmed, Aimun; Jorna, Tom; Bhandari, Sunil

doi:10.1159/000447068

Cited by 8,330 publications

(34 citation statements)

References 149 publications

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“…However, recent evidence suggests that ACEi and ARB may not be superior to other antihypertensive agents in reducing cardiovascular risk in advanced kidney disease [6] and are often associated with an increased risk of hyperkalemia, particularly when administered in combination [7]. ACEi and ARB may have different effects on potassium levels that reflect differences in their actions on potassium homeostasis.…”

Section: Introductionmentioning

confidence: 99%

Use of Renin-Angiotensin System Blockers Increases Serum Potassium in Anuric Hemodialysis Patients

Movilli¹,

Camerini²,

Gaggia³

et al. 2018

Am J Nephrol

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Background: Angiotensin converting enzyme inhibitors (ACEi) and angiotensin receptor blockers (ARB) are increasingly used in uremic patients (pts). However, their effect on serum potassium (sK) concentrations in anuric pts on chronic hemodialysis treatment (HD) is controversial. The aim of the study was to evaluate sK before and after the start of ACEi/ARB therapy. Methods: In the period 1/1/2015 – 31/12/2015, 112 out of 240 prevalent HD pts on thrice weekly HD treatment followed at our institution started the ACEi/ARB therapy. The mean age was 67 ± 14 years, 67/112 were men, dialysis vintage was 6–212 months. In the 3 months before (PRE; N° 36 HD sessions) and after (POST; N° 36 HD sessions) the start of ACEi/ARB therapy, the following variables were evaluated in pre dialysis after the long interdialysis interval: sK (mean of 12 determinations; mmol/L), maximum sK (maximum K value observed during observations; sKmax; mmol/L), serum sodium (sNa; mmol/L), pre dialysis systolic blood pressure (SBP; mm Hg) and diastolic blood pressure (DBP; mm Hg), body weight (BW; Kg), interdialytic weight gain (IWG; Kg), Kt/V, serum bicarbonate concentrations (sBic; mmol/L), protein catabolic rate (PCRn; g/KgBW/day). SBP, DBP, IWG are the mean of the 24 HD sessions. Out of 112 patients, 102 were on antihypertensive therapy. The duration of HD and blood and dialysate flow rates were kept constant. Data are expressed as mean ± SD. Student t test for paired and unpaired data for normally distributed variables, Mann-Whitney test for medians, χ² test for categorical data were employed to compare groups. A significant difference was defined as p < 0.05. Results: sK increased from 5.0 ± 0.4 mmol/L PRE to 5.7 ± 0.5 mmol/L POST (p < 0.0001). sKmax increased from 5.3 ± 0.5 mmol/L PRE to 6.2 ± 0.6 mmol/L POST (p < 0.0001). The percentage of pts with normal sK concentrations decreased from 82% PRE to 29% POST (p < 0.0001). Mild hyperkalemia increased from 18 to 52% (p < 0.001); in 31% of the patients, it was necessary to reduce the K dialysate concentration. None of the patients had severe hyperkalemia PRE, but 19% developed severe hyperkalemia POST (p < 0.0001) necessitating treatment withdrawal. Mean sK in these pts varied from 5.2 ± 0.3 mmol/L PRE to 6.5 ± 0.2 mmol/L at the moment of withdrawal (p < 0.0001) and sKmax from 5.5 ± mmol/L PRE to 6.9 ± 0.3 mmol/L (p< 0.0001). After withdrawal of ACEi/ARB, sK and sKmax concentrations decreased to basal levels within 1 month. There were no significant changes of BW, IWG, SBP, DBP, Na, Hb, Kt/V, sBic, and PCRn in both periods. Conclusions: ACEi/ARB therapy is associated with an increased risk of hyperkalemia in anuric hemodialysis patients. The proportion of patients with normal sK concentrations decreased from 82 to 29% and with mild hyperkalemia increased from 18 to 52%. Severe hyperkalemia necessitating the interruption of ACEi/ARB therapy developed in 19% of patients. This suggests great caution in the widest utilization of this class of drugs in HD patients.

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Section: Introductionmentioning

confidence: 99%

Use of Renin-Angiotensin System Blockers Increases Serum Potassium in Anuric Hemodialysis Patients

Movilli¹,

Camerini²,

Gaggia³

et al. 2018

Am J Nephrol

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“…However, ACEI and ARB are reported to be not superior to other antihypertensive drugs in patients with advanced CKD (Ahmed et al. ), and, therefore, new therapeutic strategies are needed for these patients.…”

Section: Introductionmentioning

confidence: 99%

“…Chronic kidney disease (CKD) is a life-threatening condition by progressive and irreversible loss of renal function, which subsequently leads to end-stage renal disease and causes premature mortality from cardiovascular disease (Lopez-Novoa et al 2010;Judge et al 2015). Angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin II receptor blockers (ARBs) are used for the treatment of patients with early CKD and provide better outcomes compared to those of other antihypertensive drugs (Ahmed et al 2016). However, ACEI and ARB are reported to be not superior to other antihypertensive drugs in patients with advanced CKD (Ahmed et al 2016), and, therefore, new therapeutic strategies are needed for these patients.…”

Section: Introductionmentioning

confidence: 99%

“…Angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin II receptor blockers (ARBs) are used for the treatment of patients with early CKD and provide better outcomes compared to those of other antihypertensive drugs (Ahmed et al 2016). However, ACEI and ARB are reported to be not superior to other antihypertensive drugs in patients with advanced CKD (Ahmed et al 2016), and, therefore, new therapeutic strategies are needed for these patients.…”

Section: Introductionmentioning

confidence: 99%

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Prevention against renal damage in rats with subtotal nephrectomy by sacubitril/valsartan (LCZ696), a dual‐acting angiotensin receptor‐neprilysin inhibitor

Ushijima

Ando

Arakawa

et al. 2017

Pharmacology Res & Perspec

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Although patients with chronic kidney disease (CKD) are at increased risk for end‐stage renal disease and cardiovascular events, adequate drug therapies for preventing the deterioration of these conditions are still not established. This study was undertaken to evaluate a preventive effect of an angiotensin receptor‐neprilysin inhibitor sacubitril/valsartan (LCZ696), which is converted to sacubitril and valsartan in the body, against the progression of renal disease in rats with subtotal nephrectomy, an animal model of human CKD. Mean survival time after subtotal nephrectomy was about 100 days in Wistar rats with vehicle. LCZ696‐(30 mg/kg) and valsartan‐(15 mg/kg) prolonged the survival of these animals, and the effect of LCZ696 on survival was significantly greater than that of valsartan. Renoprotective effects of LCZ696 judged by serum creatinine and urinary protein excretions were larger than those of valsartan. Cardioprotective effects judged by cardiac left ventricular mass, fractional shortening, and fibrosis of LCZ696 and valsartan were not detected under the present condition. Thus, the renoprotective effect of LCZ696 was stronger than that of valsartan in rats with subtotal nephrectomy. This study provides the idea that, compared to valsartan, LCZ696 is more effective for the treatment of human CKD.

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“…This might suggest that GPs awareness of patients' CKD status did not necessarily compel them to prescribe an ACEI/ARB. They may have other valid reasons for not prescribing, including hyperkalemia, hypotension, and acute renal injury (AKI) [28]. Among CKD patients with proteinuria who were receiving multiple antihypertensive agents, only a fifth use an ACEI/ARB in combination with a diuretic (double therapy) in this study.…”

Section: Discussionmentioning

confidence: 96%

Medication Prescribing Quality in Australian Primary Care Patients with Chronic Kidney Disease

Bezabhe

Kitsos

Saunder

et al. 2020

JCM

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Background: Australian patients with chronic kidney disease (CKD) are routinely managed in general practices with multiple medications. However, no nationally representative study has evaluated the quality of prescribing in these patients. The objective of this study was to examine the quality of prescribing in patients with CKD using nationally representative primary care data obtained from the NPS MedicineWise’s dataset, MedicineInsight. Methods: A cross-sectional analysis of general practice data for patients aged 18 years or older with CKD was performed from 1 February 2016 to 1 June 2016. The study examined the proportion of patients with CKD who met a set of 16 published indicators in two categories: (1) potentially appropriate prescribing of antihypertensives, renin-angiotensin system (RAS) inhibitors, phosphate binders, and statins; and (2) potentially inappropriate prescribing of nephrotoxic medications, such as non-steroidal anti-inflammatory drugs (NSAIDs), at least two RAS inhibitors, triple therapy (an NSAID, a RAS inhibitor and a diuretic), high-dose digoxin, and metformin. The proportion of patients meeting each quality indicator was stratified using clinical and demographic characteristics. Results: A total of 44,259 patients (24,165 (54.6%) female; 25,562 (57.8%) estimated glomerular filtration (eGFR) 45–59 mL/1.73 m2) with CKD stages 3–5 were included. Nearly one-third of patients had diabetes and were more likely to have their blood pressure and albumin-to-creatinine ratio monitored than those without diabetes. Potentially appropriate prescribing of antihypertensives was achieved in 79.9% of hypertensive patients with CKD stages 4–5. The prescribing indicators for RAS inhibitors in patients with microalbuminuria and diabetes and in patients with macroalbuminuria were achieved in 69.9% and 62.3% of patients, respectively. Only 40.8% of patients with CKD and aged between 50 and 65 years were prescribed statin therapy. The prescribing of a RAS inhibitor plus a diuretic was less commonly achieved, with the indicator met in 20.6% for patients with microalbuminuria and diabetes and 20.4% for patients with macroalbuminuria. Potentially inappropriate prescribing of NSAIDs, metformin, and at least two RAS inhibitors were apparent in 14.3%, 14.1%, and 7.6%, respectively. Potentially inappropriate prescribing tended to be more likely in patients aged ≥65 years, living in regional or remote areas, or with socio-economic indexes for areas (SEIFA) score ≤ 3. Conclusions: We identified areas for possible improvement in the prescribing of RAS inhibitors and statins, as well as deprescribing of NSAIDs and metformin in Australian general practice patients with CKD.

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Should We STOP Angiotensin Converting Enzyme Inhibitors/Angiotensin Receptor Blockers in Advanced Kidney Disease?

Cited by 8,330 publications

References 149 publications

Use of Renin-Angiotensin System Blockers Increases Serum Potassium in Anuric Hemodialysis Patients

Use of Renin-Angiotensin System Blockers Increases Serum Potassium in Anuric Hemodialysis Patients

Prevention against renal damage in rats with subtotal nephrectomy by sacubitril/valsartan (LCZ696), a dual‐acting angiotensin receptor‐neprilysin inhibitor

Medication Prescribing Quality in Australian Primary Care Patients with Chronic Kidney Disease

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