Abstract
Purpose
Tolvaptan, a vasopressin V2 receptor antagonist, slows the decline in renal function in autosomal dominant polycystic kidney disease (ADPKD). However, it increases urine output such that patient adherence could be compromised. In a cohort of patients with ADPKD on tolvaptan, we aimed to identify the contribution of sodium and urea excretion rate to daily urine output, and to evaluate the effectiveness of dietary counseling on sodium and urea excretion rates.
Methods
Retrospective analysis of 30 ADPKD patients who underwent a single session of personalized dietary counseling to reduce sodium and protein intake before initiation of tolvaptan. Creatinine and 24-h urine were obtained regularly on treatment. Generalized estimation equations were used.
Results
Mean age and median eGFR were 44 ± 11 years and 52 (43–74) ml/min/1.73 m2. Tolvaptan increased diuresis from 2.5 to 5.2 l/day. After adjusting for the dose of tolvaptan, an increase in sodium and urea excretion rate by 50 mmol/day was associated with an estimated additional urine volume of 0.6 l/day (95% CI 0.4–0.8 l/day; P < 0.001) and 0.25 l/day (95% CI 0.11–0.39 l/day; P < 0.001), respectively. Dietary counseling resulted in a transient reduction of sodium excretion by 19 mmol/day during the first 4 months (P = 0.016) but resulted in a more sustained reduction in urea excretion by 69 mmol/day (P = 0.008).
Conclusion
Both sodium and urea excretion rates contribute significantly to daily urine volume in patients treated with tolvaptan, and a single session of dietary counseling was transiently effective in reducing sodium intake but achieved a more sustained reduction in protein intake. Dietary counseling should be considered in the management of ADPKD patients treated by tolvaptan.
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References
Spithoven EM, Kramer A, Meijer E, Orskov B, Wanner C, Abad JM, Areste N, de la Torre RA, Caskey F, Couchoud C, Finne P, Heaf J, Hoitsma A, de Meester J, Pascual J, Postorino M, Ravani P, Zurriaga O, Jager KJ, Gansevoort RT, Registry E-E, Euro CC (2014) Renal replacement therapy for autosomal dominant polycystic kidney disease (adpkd) in Europe: prevalence and survival—an analysis of data from the era-edta registry. Nephrol Dial Transplant 29(Suppl 4):iv15–iv25
The European Polycystic Kidney Disease Consortium (1994) The polycystic kidney disease 1 gene encodes a 14 kb transcript and lies within a duplicated region on chromosome 16. Cell 78:725
Mochizuki T, Wu G, Hayashi T, Xenophontos SL, Veldhuisen B, Saris JJ, Reynolds DM, Cai Y, Gabow PA, Pierides A, Kimberling WJ, Breuning MH, Deltas CC, Peters DJM, Somlo S (1996) Pkd2, a gene for polycystic kidney disease that encodes an integral membrane protein. Science 272:1339–1342
Torres VE, Harris PC (2009) Autosomal dominant polycystic kidney disease: the last 3 years. Kidney Int 76:149–168
Reif GA, Yamaguchi T, Nivens E, Fujiki H, Pinto CS, Wallace DP (2011) Tolvaptan inhibits erk-dependent cell proliferation, cl(-) secretion, and in vitro cyst growth of human adpkd cells stimulated by vasopressin. Am J Physiol Renal Physiol 301:F1005–1013
Torres VE, Chapman AB, Devuyst O, Gansevoort RT, Grantham JJ, Higashihara E, Perrone RD, Krasa HB, Ouyang J, Czerwiec FS, Investigators TT (2012) Tolvaptan in patients with autosomal dominant polycystic kidney disease. N Engl J Med 367:2407–2418
Torres VE, Chapman AB, Devuyst O, Gansevoort RT, Perrone RD, Koch G, Ouyang J, McQuade RD, Blais JD, Czerwiec FS, Sergeyeva O, Investigators RT (2017) Tolvaptan in later-stage autosomal dominant polycystic kidney disease. N Engl J Med 377:1930–1942
Soroka S, Alam A, Bevilacqua M, Girard LP, Komenda P, Loertscher R, McFarlane P, Pandeya S, Tam P, Bichet DG (2018) Updated Canadian expert consensus on assessing risk of disease progression and pharmacological management of autosomal dominant polycystic kidney disease. Can J Kidney Health Dis 5:2054358118801589
Kramers BJ, van Gastel MDA, Boertien WE, Meijer E, Gansevoort RT (2019) Determinants of urine volume in adpkd patients using the vasopressin v2 receptor antagonist tolvaptan. Am J Kidney Dis 73:354–362
Irazabal MV, Rangel LJ, Bergstralh EJ, Osborn SL, Harmon AJ, Sundsbak JL, Bae KT, Chapman AB, Grantham JJ, Mrug M, Hogan MC, El-Zoghby ZM, Harris PC, Erickson BJ, King BF, Torres VE, Investigators C (2015) Imaging classification of autosomal dominant polycystic kidney disease: a simple model for selecting patients for clinical trials. J Am Soc Nephrol 26:160–172
Levey AS, Stevens LA, Schmid CH, Zhang YL, Castro AF 3rd, Feldman HI, Kusek JW, Eggers P, Van Lente F, Greene T, Coresh J, Ckd EPI (2009) A new equation to estimate glomerular filtration rate. Ann Intern Med 150:604–612
Irazabal MV, Blais JD, Perrone RD, Gansevoort RT, Chapman AB, Devuyst O, Higashihara E, Harris PC, Zhou W, Ouyang J, Czerwiec FS, Torres VE (2016) Prognostic enrichment design in clinical trials for autosomal dominant polycystic kidney disease: the tempo 3:4 clinical trial. Kidney Int Rep 1:213–220
Higashihara E, Torres VE, Chapman AB, Grantham JJ, Bae K, Watnick TJ, Horie S, Nutahara K, Ouyang J, Krasa HB, Czerwiec FS (2011) Tempoformula, Study I. Tolvaptan in autosomal dominant polycystic kidney disease: three years' experience. Clin J Am Soc Nephrol 6:2499–2507
Irazabal MV, Torres VE, Hogan MC, Glockner J, King BF, Ofstie TG, Krasa HB, Ouyang J, Czerwiec FS (2011) Short-term effects of tolvaptan on renal function and volume in patients with autosomal dominant polycystic kidney disease. Kidney Int 80:295–301
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F Mac-Way holds scholarships from the Fonds de Recherche Québec-Santé.
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FM has received conference honoraria from Amgen and Sanofi, and received consultative honoraria from Otsuka; CL and MA have received consultative honoraria from Otsuka; PRC has received honoraria for consultation and CMEs from Otsuka Canada.
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Côté, G., Asselin-Thompstone, L., Mac-Way, F. et al. Sodium and urea excretion as determinants of urine output in autosomal dominant polycystic kidney disease patients on V2 receptor antagonists: impact of dietary intervention. Int Urol Nephrol 52, 343–349 (2020). https://doi.org/10.1007/s11255-020-02384-3
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DOI: https://doi.org/10.1007/s11255-020-02384-3