Tolvaptan alleviates excessive fluid retention of nephrotic diabetic renal failure unresponsive to furosemide

Abstract

Patients with diabetic nephropathy develop nephrotic syndrome and may show limited response to conventional therapy. They often require earlier initiation of renal replacement therapy because they become refractory to diuretics, and experience excessive fluid retention. We aimed to investigate the efficacy of tolvaptan, an oral arginine vasopressin type 2 receptor antagonist, in a case series of 14 severe diabetic renal failure patients who were severely refractory to maximal doses of furosemide and had excessive fluid retention despite preserved cardiac function and residual renal function. All 14 patients experienced immediate and sustained water diuretic effects, resulting in alleviation of congestive heart failure. None required initiation of renal replacement therapy. Tolvaptan promptly increased urine volume and free water clearance, reversed progressive fluid retention, and alleviated congestive heart failure. Thus, tolvaptan could serve as a potential adjunct therapy for severe diabetic renal failure patients with excessive fluid retention and congestive heart failure.

Rethinking Vasopressin: New Insights into Vasopressin Signaling and Its Implications

“…81 In fact a provocative study showed that in diabetic patients with severe fluid retention despite treatment with loop diuretics, the addition of a V2R antagonist (tolvaptan) resulted in significant diuresis and improved decongestion. 82 This supports the notion that vasopressin plays a key role in volume retention associated with diabetic nephropathy. In addition, there are data that suggest that the interaction between vasopressin, insulin, and glucose plays a key role in the progression of kidney disease.…”

Different Effects on Fluid Distribution between Tolvaptan and Furosemide in a Liver Cirrhosis Patient with Chronic Kidney Disease

“…Tolvaptan is reportedly effective for ameliorating fluid retention in patients with liver cirrhosis with ascites (17,18) and advanced CKD (8,19,20), but a low serum sodium level (＜130 mEq/L) is associated with non-responsiveness to tolvaptan (18). In addition, recent studies have shown that tolvaptan exerts a diuretic action even in patients with low serum albumin levels (18,21,22). Because tolvaptan blocks the vasopressin V2 receptor from the basolateral side of the tubules, it is not dependent on the GFR provided the renal blood flow (RBF) is maintained (2).…”

Impaired Renal Function May Not Negate the Efficacy of Tolvaptan in the Treatment of Cirrhotic Patients with Refractory Ascites

“…Moreover, many patients with s-CKD revealed proteinuria in the spot urine test, demonstrating the presence of diabetic nephropathy. Several reports state that tolvaptan is effective against diabetic nephropathy associated with fluid retention in CKD patients [40–42]. Tolvaptan acts on the collecting ducts, which are relatively preserved in ischemic renal diseases caused by diabetes, so the effects of tolvaptan are readily demonstrated.…”