High dose Telmisartan may help reduce proteinuria in CKD Patients: Study
Renoprotective therapy, including inhibition of the renin-angiotensin system (RAS), in patients with chronic kidney disease (CKD) is important to support renal function, especially in patients with overt proteinuria. In a recent study, researchers have found that the high dose of telmisartan, an angiotensin II receptor blockers (ARBs) significantly reduces the proteinuria. However, the renoprotective effect of ARBs may be limited in CKD patients with non-nephrotic proteinuria. The study findings were published in the journal SAGE Open Medicine on November 23, 2020.
Several previous studies have demonstrated that RAS inhibition by ARBs may exert renoprotective effects in a dose-dependent manner. For example, 300 mg irbesartan exerts stronger effects than 150 mg irbesartan in terms of urinary albumin excretion and overt diabetic nephropathy prevention. However, In those studies, none of the participants had moderate to severe renal insufficiency, such as CKD stage 3–4; only one study investigated dose-dependent renoprotection in patients with moderate to severe CKD and found a higher degree of proteinuria. Although angiotensin II receptor blockers are effective for patients with chronic kidney disease, dose-dependent renoprotective effects of angiotensin II receptor blockers in patients with moderate to severe chronic kidney disease with non-nephrotic proteinuria are not known. Therefore, researchers of the Nagasaki University Hospital, Japan conducted a study to clarify the dose-dependent renoprotective effect and safety of the long-term administration of the ARB telmisartan on patients with stage 3 or 4 CKD without nephrotic level proteinuria.
The JINNAGA study was a multicenter, prospective, randomized trial, conducted from 2009 to 2014. A total of 61 patients with non-nephrotic stage 3–4 chronic kidney disease were randomly assigned to receive either 40mg (n=32) or 80 mg (n=29) telmisartan and were observed for up to 104 weeks. The major outcome assessed was renal death, doubling of serum creatinine level, the transition to stage 5 chronic kidney disease and death from any cause. Researchers also assessed the level of urinary proteins and changes in the estimated glomerular filtration rate.
Upon analysis, researchers found no significant difference in the primary outcome and eGFR between the two groups. However, after 24 weeks, they noted a significant reduction in the level of proteinuria among 80 mg group than in the 40 mg group. They noted no severe adverse events occurred in either group, and the occurrence of adverse events did not significantly differ between them.
The authors concluded, "Our findings do not demonstrate a direct dose-dependent renoprotective effect of telmisartan. The higher telmisartan dose resulted in a decrease in the amount of urinary protein. Even though high-dose angiotensin II receptor blockers may be preferable for patients with stage 3–4 chronic kidney disease, the clinical importance of the study results may be limited".
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