Efficacy of tolvaptan on nephrotic patients with diuretic-resistant edema: a pilot study

Abstract

Background Tolvaptan (TLV), a vasopressin type 2 receptor antagonist, is an effective drug for heart failure without worsening renal function. However, the effect of TLV on nephrotic syndrome remains unknown. This study aims to assess the association between response to TLV and clinical parameters including pathological evaluation in nephrotic patients with diuretics-resistance.Methods For prospectively enrolled patients, TLV was added for 14 days after renal biopsy performed. We evaluated the effect of TLV on urine output (UO) and body weight (BW) and the correlation of UO change with BW, urine and blood measurements and pathological evaluation. Pathological evaluation included glomerular sclerosis, tubulointerstitial injury, interstitial fibrosis and the degree of aquaporin 2 (AQP2) positivity in collecting ducts.Results Ten nephrotic patients were enrolled. Two patients already received 140 and 160mg furosemide and others 40mg furosemide before TLV. After TLV administration, no patients showed worsening renal function or hypernatremia (>145 mEq/L) and two patients without any improvement of symptoms discontinued the trial. TLV significantly increased UO at day 1 and decreased BW overall. UO increase at day 1 was significantly correlated with BW decrease at the last follow-up. UO increase at day 1 was correlated only with AQP2 positivity in collecting ducts on biopsied kidney (r2=0.59, p=0.01) while other urine and blood measurements were not. Conclusions TLV was effective on nephrotic patients. UO increase by TLV was correlated with AQP2 positivity in the collecting ducts while biochemistry in urine and blood was not.