aliskiren and Acute-Kidney-Injury

To examine the safety of using aliskiren combined with agents used to block the renin-angiotensin system.. Systematic review and meta-analysis of randomised controlled trials.. Medline, Embase, the Cochrane Library, and two trial registries, published up to 7 May 2011.. Published and unpublished randomised controlled trials that compared combined treatment using aliskiren and angiotensin converting enzyme inhibitors or angiotensin receptor blockers with monotherapy using these agents for at least four weeks and that provided numerical data on the adverse event outcomes of hyperkalaemia and acute kidney injury. A random effects model was used to calculate pooled risk ratios and 95% confidence intervals for these outcomes.. 10 randomised controlled studies (4814 participants) were included in the analysis. Combination therapy with aliskiren and angiotensin converting enzyme inhibitors or angiotensin receptor blockers significantly increased the risk of hyperkalaemia compared with monotherapy using angiotensin converting enzymes or angiotensin receptor blockers (relative risk 1.58, 95% confidence interval 1.24 to 2.02) or aliskiren alone (1.67, 1.01 to 2.79). The risk of acute kidney injury did not differ significantly between the combined therapy and monotherapy groups (1.14, 0.68 to 1.89).. Use of aliskerin in combination with angiotensin converting enzyme inhibitors or angiotensin receptor blockers is associated with an increased risk for hyperkalaemia. The combined use of these agents warrants careful monitoring of serum potassium levels.

Topics: Acute Kidney Injury; Amides; Angiotensin-Converting Enzyme Inhibitors; Antihypertensive Agents; Drug Therapy, Combination; Fumarates; Humans; Hyperkalemia; Randomized Controlled Trials as Topic

In 2012, the European Medicines Agency reviewed the safety of dual renin-angiotensin system (RAS) blockade because of potentially increased risks for inter alia acute kidney injury (AKI). Since residents of nursing homes are particularly vulnerable to adverse drug outcomes, the aims of our study were to describe RAS-inhibiting drug use in German nursing home residents and examine the risk of AKI associated with dual RAS blockade.. Based on claims data, a nested case-control study within a cohort of RAS-inhibiting drug users was conducted. Using conditional logistic regression, confounder-adjusted odds ratios (aORs) and 95% confidence intervals (CI) were obtained for the risk of AKI associated with dual RAS blockade. Subgroup analyses were performed in patients with diabetes or chronic kidney disease and both comorbidities.. Of all 127,227 nursing home residents, the study cohort included 64,567 (50.7%) who were treated with at least one RAS-inhibiting drug. More than three quarters of the study population were female (77.1%). Mean age was 86.0 ± 6.8 years. Most residents were treated with angiotensin-converting enzyme inhibitors (77.8%), followed by angiotensin II receptor blockers (21.6%) and aliskiren (0.2%). Annual prevalence of dual RAS blockade declined from 9.6 (95% CI 7.8-11.8) in 2010 to 4.7 (95% CI 4.0-5.4) per 1,000 users in 2014. In the overall cohort, AKI was not significantly associated with dual RAS blockade (aOR 1.99; 0.77-5.17). However, significantly increased aORs were observed when considering patients with diabetes (3.47; 1.27-9.47), chronic kidney disease (4.74; 1.24-18.13) or both (11.17; 2.65-47.15).. Prescribing of drugs inhibiting the RAS is common in German nursing homes. Though the prevalence of dual RAS blockade declined, our study showed an increased risk of AKI in patients with diabetes and/or chronic kidney disease. Therefore, cautious use is warranted in these vulnerable patients.

Topics: Acute Kidney Injury; Aged; Aged, 80 and over; Amides; Angiotensin Receptor Antagonists; Angiotensin-Converting Enzyme Inhibitors; Antihypertensive Agents; Case-Control Studies; Cohort Studies; Diabetes Mellitus; Drug Prescriptions; Drug Therapy, Combination; Female; Fumarates; Germany; Humans; Male; Nursing Homes; Renal Insufficiency, Chronic; Renin-Angiotensin System; Risk Factors

Topics: Acute Kidney Injury; Amides; Angiotensin Receptor Antagonists; Angiotensin-Converting Enzyme Inhibitors; Female; Fumarates; Humans; Hyperkalemia; Male; Stroke

Some evidence suggests that the direct renin inhibitor aliskiren may increase the risk of severe hyperkalemia, stroke, or acute kidney injury (AKI) when prescribed with angiotensin-converting enzyme inhibitors (ACEi's) or angiotensin-receptor blockers (ARBs). The extent to which concomitant treatment increases the risk of these outcomes in routine clinical practice is unknown. We addressed this issue with the use of administrative databases.. We established a cohort of Ontarians treated with an ACEi or an ARB. Within this cohort, we conducted 3 case-control studies. Cases were patients hospitalized with 1 of 3 outcomes (hyperkalemia, AKI, or stroke). In each analysis, we identified up to 5 matched control subjects for each case. Conditional logistic regression was used to examine the association between hospitalization for each outcome and the use of aliskiren in the preceding 60 days.. Among 903,346 patients aged 66 years and older treated with an ACEi or ARB during the 28-month study period, we identified 4235 hospitalized with hyperkalemia, 18,231 hospitalized with AKI, and 8283 hospitalized with stroke. After extensive multivariable adjustment, aliskiren therapy was not associated with a significant increase in the risk of hospitalization for hyperkalemia, AKI, or stroke. We found similar results in stratified analyses of patients with and without a history of chronic kidney disease, diabetes, or heart failure.. Among community-dwelling patients aged 66 years and older receiving therapy with an ACEi or an ARB, aliskiren use was not associated with hospitalization for hyperkalemia, AKI, or stroke.

Topics: Acute Kidney Injury; Aged; Aged, 80 and over; Amides; Angiotensin Receptor Antagonists; Angiotensin-Converting Enzyme Inhibitors; Case-Control Studies; Cohort Studies; Drug Therapy, Combination; Female; Fumarates; Hospitalization; Humans; Hyperkalemia; Logistic Models; Male; Ontario; Renin; Risk Factors; Stroke

We report a case of acute kidney injury (AKI) caused by a novel direct renin inhibitor, aliskiren. A 43-year-old Japanese man with dilated cardiomyopathy on cardiac resynchronization therapy with defibrillator and chronic kidney disease (CKD) was started on aliskiren in addition to enalapril, carvedilol, furosemide, and spironolactone for worsening cardiac function suggested by the elevation of serum brain natriuretic peptide. After 1 month, he noticed general malaise, loss of appetite and his serum creatinine level increased from 2.0 to 7.24 mg/dL. He had no evidence of exacerbation of hemodynamic instability (heart failure or hypotension) or post-renal cause of AKI. Although a cessation of aliskiren did not ameliorate AKI, renal function returned to baseline after withholding enalapril. Careful monitoring is necessary when aliskiren is used in patients with CKD and/or significant systolic dysfunction since it can cause normotensive ischemic AKI, especially when there is a concomitant use of other renin-angiotensin-aldosterone system inhibitors.

Topics: Acute Kidney Injury; Adult; Amides; Antihypertensive Agents; Cardiomyopathy, Dilated; Fumarates; Humans; Kidney Failure, Chronic; Male; Natriuretic Peptide, Brain

Enhanced renin-angiotensin-aldosterone system (RAAS) activation contributes to proteinuria and chronic kidney disease by increasing glomerular and tubulointerstitial oxidative stress, promotion of fibrosis. Renin activation is the rate limiting step in angiotensin (Ang II) and aldosterone generation, and recent work suggests direct renin inhibition improves proteinuria comparable to that seen with Ang type 1 receptor (AT(1)R) blockade. This is important as, even with contemporary use of AT(1)R blockade, the burden of kidney disease remains high. Thereby, we sought to determine if combination of direct renin inhibition with AT(1)R blockade in vivo, via greater attenuation of kidney oxidative stress, would attenuate glomerular and proximal tubule injury to a greater extent than either intervention alone. We utilized the transgenic Ren2 rat with increased tissue RAS activity and higher serum levels of aldosterone, which manifests hypertension and proteinuria. Ren2 rats were treated with renin inhibition (aliskiren), AT(1)R blockade (valsartan), the combination (aliskiren+valsartan), or vehicle for 21days. Compared to Sprague-Dawley controls, Ren2 rats displayed increased systolic pressure (SBP), circulating aldosterone, proteinuria and greater urine levels of the proximal tubule protein excretory marker beta-N-acetylglucosaminidase (β-NAG). These functional and biochemical alterations were accompanied by increases in kidney tissue NADPH oxidase subunit Rac1 and 3-nitrotyrosine (3-NT) content as well as fibronectin and collagen type III. These findings occurred in conjunction with reductions in the podocyte-specific protein podocin as well as the proximal tubule-specific megalin. Further, in transgenic animals there was increased tubulointerstitial fibrosis on light microscopy as well as ultrastructural findings of glomerular podocyte foot-process effacement and reduced tubular apical endosomal/lysosomal activity. Combination therapy led to greater reductions in SBP and serum aldosterone, but did not result in greater improvement in markers of glomerular and tubular injury (i.e. β-NAG) compared to either intervention alone. Further, combination therapy did not improve markers of oxidative stress and podocyte and proximal tubule integrity in this transgenic model of RAAS-mediated kidney damage despite greater reductions in serum aldosterone and BP levels.

Topics: Acute Kidney Injury; Aldosterone; Amides; Angiotensin II Type 1 Receptor Blockers; Animals; Fumarates; Rats; Rats, Sprague-Dawley; Rats, Transgenic; Receptor, Angiotensin, Type 1; Renin; Tetrazoles; Valine; Valsartan

We report the first case of acute renal failure with hyperkalemia associated with the recently marketed direct renin inhibitor aliskiren. To optimize blood pressure control, the antihypertensive medication of a 76-year-old hypertensive female patient was changed from the angiotensin II receptor antagonist irbesartan to aliskiren. Spironolactone was continued, as serum creatinine and potassium levels were initially normal. Two weeks later the patient presented with acute oliguric renal failure, symptomatic hyperkalemia and metabolic acidosis, necessitating emergency dialytic treatment. Unrecognized pre-existing renal insufficiency (CKD Stage 2 - 3) and the continuation of spironolactone were identified as predisposing risk factors.

Topics: Acute Kidney Injury; Aged; Amides; Antihypertensive Agents; Female; Fumarates; Humans; Hyperkalemia; Hypertension; Renal Dialysis