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Efficacy and Safety of Combination Therapy with Tolvaptan and Furosemide in Children with Nephrotic Syndrome and Refractory Edema: A Prospective Interventional Study

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Abstract

Objective

Severe edema in children with nephrotic syndrome is often refractory to conventional diuretics. Tolvaptan has been used satisfactorily for managing edema in patients with heart failure and cirrhosis. The safety and efficacy of combination therapy with oral tolvaptan and intravenous (IV) furosemide was assessed in patients with furosemide refractory edema.

Methods

Patients, aged 5–18 y with nephrotic syndrome and severe edema, were screened for eligibility. After excluding hypovolemia, patients received IV furosemide (3–4 mg/kg/d) for 48 h. Those refractory to IV furosemide (weight loss < 3%) received tolvaptan (0.5–1 mg/kg once daily) and IV furosemide for the next 48 h. Parameters were compared between 48 h of furosemide alone and combination therapy.

Results

A total of 24 patients (18 boys) with mean age of 8.0 ± 3.0 y were enrolled. Urine volume significantly increased with combination therapy as compared to furosemide therapy (mean difference: 1.2 mL/kg/h; 95% CI: 0.8–1.65 mL/kg/h) (p < 0.001). Compared to therapy with furosemide alone, combination therapy resulted in significant reduction in body weight from 26.9 ± 10.3 kg to 24.8 ± 9.7 kg (p < 0.001). Estimated glomerular filtration rate did not change (p = 0.81) but serum sodium increased from 135.7 ± 3.3 mEq/L to 140.4 ± 4.8 mEq/L (p < 0.001) with combination therapy; 2 patients showed asymptomatic hypernatremia.

Conclusion

The combination of oral tolvaptan and IV furosemide is effective in augmenting diuresis and reducing weight in patients with furosemide refractory edema but requires monitoring of electrolytes and volume status.

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Acknowledgements

Study medication was provided free of cost by MSN laboratories limited. The company had no role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; preparation, review, or approval of the manuscript; and decision to submit the manuscript for publication. This study was also supported by Indian Council of Medical Research [Advanced Centre for Research in Pediatric Kidney Diseases; 5/7/1090/2013-RHN].

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Authors and Affiliations

  1. Division of Nephrology, Department of Pediatrics, ICMR Center for Advanced Research in Nephrology, All India Institute of Medical Sciences, New Delhi, 110029, India

    Jitendra Meena, Pankaj Hari, Aditi Sinha & Arvind Bagga

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  1. Jitendra Meena
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  2. Pankaj Hari
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  3. Aditi Sinha
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Contributions

All authors contributed to the study conception and design. Conceptualization is by JM and PH. Material preparation, data collection, and analysis were performed by JM and AS. The first draft of the manuscript was written by JM, AB, and PH edited on previous versions of the manuscript. All authors read and approved the final manuscript. PH will act as guarantor for the manuscript.

Corresponding author

Correspondence to Pankaj Hari.

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Ethical Approval

Ethical approval for this study was obtained from the institutional ethics committee of All Institute of Medical Sciences, New Delhi (IECPG-161/23.08.2017, RT-35/07.09.2017) and all procedures performed in studies were in accordance with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.

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Meena, J., Hari, P., Sinha, A. et al. Efficacy and Safety of Combination Therapy with Tolvaptan and Furosemide in Children with Nephrotic Syndrome and Refractory Edema: A Prospective Interventional Study. Indian J Pediatr 89, 699–705 (2022). https://doi.org/10.1007/s12098-021-03988-y

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