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Original ArticlesNephrolithiasis
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Urinary Lithogenic Risk Profile in ADPKD Patients Treated with Tolvaptan

Matteo Bargagli, Nasser A. Dhayat, Manuel Anderegg, Mariam Semmo, Uyen Huynh-Do, Bruno Vogt, Pietro Manuel Ferraro and Daniel G. Fuster
CJASN July 2020, 15 (7) 1007-1014; DOI: https://doi.org/10.2215/CJN.13861119
Matteo Bargagli
1U.O.C. Nefrologia, Fondazione Policlinico Universitario A. Gemelli IRCCS, Rome, Italy
2Università Cattolica del Sacro Cuore, Rome, Italy
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Nasser A. Dhayat
3Department of Nephrology and Hypertension, Inselspital, Bern University Hospital, University of Bern, Bern, Switzerland
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Manuel Anderegg
3Department of Nephrology and Hypertension, Inselspital, Bern University Hospital, University of Bern, Bern, Switzerland
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Mariam Semmo
3Department of Nephrology and Hypertension, Inselspital, Bern University Hospital, University of Bern, Bern, Switzerland
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Uyen Huynh-Do
3Department of Nephrology and Hypertension, Inselspital, Bern University Hospital, University of Bern, Bern, Switzerland
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Bruno Vogt
3Department of Nephrology and Hypertension, Inselspital, Bern University Hospital, University of Bern, Bern, Switzerland
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Pietro Manuel Ferraro
1U.O.C. Nefrologia, Fondazione Policlinico Universitario A. Gemelli IRCCS, Rome, Italy
2Università Cattolica del Sacro Cuore, Rome, Italy
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Daniel G. Fuster
3Department of Nephrology and Hypertension, Inselspital, Bern University Hospital, University of Bern, Bern, Switzerland
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Abstract

Background and objectives Nephrolithiasis is a common health problem in autosomal dominant polycystic kidney disease (ADPKD) and significantly contributes to patient morbidity. Recently, Tolvaptan has been introduced for the treatment of ADPKD, but whether it is associated with alterations of the urinary lithogenic risk profile remains unknown.

Design, setting, participants, & measurements We conducted an analysis of participants enrolled in the Bern ADPKD registry, a prospective observational cohort study. Twenty-four-hour urine analyses were performed at baseline and then at yearly follow-ups. Relative supersaturation ratios for calcium oxalate, brushite, and uric acid were calculated with the program EQUIL2. Unadjusted and multivariable mixed-effects linear regression models, adjusted for age, sex, body mass index, eGFR, net acid excretion, and height-adjusted total kidney volume, were used to assess the association of Tolvaptan with urinary parameters relevant for kidney stone formation. The maximum individual follow-up time was 3 years, median follow-up time 1.9 years, and cumulative follow-up time 169 years.

Results In total, 125 participants (38 with and 87 without Tolvaptan treatment) were included in the analysis. In multivariable analysis, Tolvaptan treatment was associated [adjusted estimate of the difference between Tolvaptan and no Tolvaptan; 95% confidence interval (CI)] with lower urine relative supersaturation ratios for calcium oxalate (−0.56; 95% CI, −0.82 to −0.3; P<0.001), brushite (−0.33; 95% CI, −0.54 to −0.11; P=0.004), and uric acid (−0.62; 95% CI, −0.88 to −0.37; P<0.001), and with higher urine citrate in mmol/mmol creatinine per day (0.25; 95% CI, 0.05 to 0.46; P=0.02) and calcium in mmol/mmol creatinine per day (0.31; 95% CI, 0.09 to 0.53; P=0.006) excretion. In addition, Tolvaptan treatment was associated with lower net acid excretion in mEq/mmol creatinine per day (−0.54; 95% CI, −0.90 to −0.17; P=0.004) and higher net gastrointestinal alkali absorption in mEq/mmol creatinine per day (0.57; 95% CI, 0.26 to 0.88; P<0.001).

Conclusions Tolvaptan treatment is associated with a significantly improved urinary lithogenic risk profile in patients with ADPKD.

  • ADPKD
  • kidney stones
  • tolvaptan
  • calcium oxalate
  • polycystic kidney
  • autosomal dominant
  • creatinine
  • glomerular filtration rate
  • uric acid
  • calcium phosphate
  • dibasic
  • dihydrate
  • linear models
  • citric acid
  • body mass index
  • alkalies
  • prospective studies
  • cohort studies
  • follow-up studies
  • kidney calculi
  • Received November 14, 2019.
  • Accepted April 24, 2020.
  • Copyright © 2020 by the American Society of Nephrology
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Clinical Journal of the American Society of Nephrology: 15 (7)
Clinical Journal of the American Society of Nephrology
Vol. 15, Issue 7
July 01, 2020
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Urinary Lithogenic Risk Profile in ADPKD Patients Treated with Tolvaptan
Matteo Bargagli, Nasser A. Dhayat, Manuel Anderegg, Mariam Semmo, Uyen Huynh-Do, Bruno Vogt, Pietro Manuel Ferraro, Daniel G. Fuster
CJASN Jul 2020, 15 (7) 1007-1014; DOI: 10.2215/CJN.13861119

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Urinary Lithogenic Risk Profile in ADPKD Patients Treated with Tolvaptan
Matteo Bargagli, Nasser A. Dhayat, Manuel Anderegg, Mariam Semmo, Uyen Huynh-Do, Bruno Vogt, Pietro Manuel Ferraro, Daniel G. Fuster
CJASN Jul 2020, 15 (7) 1007-1014; DOI: 10.2215/CJN.13861119
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Keywords

  • ADPKD
  • kidney stones
  • tolvaptan
  • calcium oxalate
  • polycystic kidney
  • autosomal dominant
  • creatinine
  • glomerular filtration rate
  • uric acid
  • calcium phosphate
  • dibasic
  • dihydrate
  • linear models
  • citric acid
  • Body Mass Index
  • alkalies
  • Prospective Studies
  • cohort studies
  • follow-up studies
  • kidney calculi

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