Two kidney transplant patients on ciclosporin developed acute renal failure 10 to 42 days after starting to take enalapril 5 to 10mg twice daily. Recovery was complete when enalapril was stopped in one of patients, and when both enalapril and ciclosporin were stopped in other. The latter patient had no problems when ciclosporin was restarted. Both recovered renal function after 10 to 30 days. Neither had any previous evidence of renal artery stenosis or chronic rejection,which are conditions known to predispose to renal failure during ACE inhibitor treatment. Two other patients appeared to tolerate concurrent use well (See reference number 1). Two further kidney transplant patients developed acute renal failure when given enalapril. Neither had renal arterial stenosis or acute rejection (See reference number 2). The manufacturer briefly mentions that transient oliguria was seen in a kidney transplant patient given ciclosporin and captopril (See reference number 3).
0.2 mmol/L). Potassium levels were not increased above 5.5 mmol/L in any of patients studied. Uric acid levels were also increased by enalapril but decreased by losartan,although this was not statistically significant. No changes in ciclosporin trough levels were seen during study and serum creatinine remained stable (See reference number 4). Another study in kidney transplant patients taking ciclosporin with either enalapril (33 patients) or enalapril plus amlodipine (32 patients) found that potassium and serum creatinine levels did not increase in enalapril/amlodipine group whereas they increased by 0.2 mmol/L and 9 micromol/L, respectively, in group who received enalapril alone. Ciclosporin levels remained stable in all patients (See reference number 5).
A study in kidney transplant patients taking ciclosporin with losartan found that serum creatinine was only slightly and non-significantly increased in 5 patients
5 mmol/L) developed in 4 patients but potassium had fallen to below
5.5 mmol/L by week 12 in all patients. Ciclosporin levels were remained stable during study and no significant dose changes were made, although one patient was withdrawn from study due to ciclosporin toxicity which authors state was not related to use of losartan (See reference number 6). Another study in 14 kidney transplant patients taking ciclosporin with losartan 50 to 100mg daily for 8 weeks found serum creatinine,potassium and ciclosporin levels were unaffected (See reference number 7). Another study in 41 kidney transplant patients with proteinuria taking ciclosporin found that addition of candesartan 4 to 12mg daily had no significant effects on creatinine clearance or ciclosporin levels (See reference number 8).
Not understood. One suggestion is that ciclosporin reduces renal blood flow and reduces perfusion through glomerulus, which is worsened when angiotensin II is inhibited by ACE inhibitor (See reference number 1). One study suggested that larger increase in potassium levels may be related to changes in aldosterone levels seen with enalapril (See reference number 4).
There have been few specific case reports of renal failure and hyperkalaemia with ciclosporin and ACE inhibitors or angiotensin II receptor antagonists. Data from efficacy studies above suggest that incidence of renal failure and hyperkalaemia is low, nevertheless care and good monitoring are needed if ACE inhibitors or angiotensin II receptor antagonists and ciclosporin are used concurrently. Also note that manufacturers of ciclosporin warn about possible risk of hyperkalaemia with ACE inhibitors and angiotensin II receptor antagonists with ciclosporin as these drugs may raise potassium levels (See reference number 9). Monitor potassium levels more closely in initial weeks of concurrent use, bearing in mind that an increase in potassium levels may be due to worsening renal function as well as these drugs.
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