Response to Alkali Administration in Women and Men With and Without CKD

Alkali therapy may limit the progression of chronic kidney disease (CKD)1Gianella F.G. Prado V.E. Poindexter J.R. et al.Spot urinary citrate-to-creatinine ratio is a marker for acid-base status in disease.Kidney Int. 2021; 99: 208-217Abstract Full Text PDF PubMed Scopus (18) Google Scholar, 2Goraya N. Simoni J. Sager L.N. Madias N.E. Wesson D.E. Urine citrate excretion as acid retention patients with without overt metabolic acidosis.Kidney 2019; 95: 1190-1196Abstract (51) 3Di Iorio B.R. Bellasi A. Raphael K.L. al.Treatment acidosis sodium bicarbonate delays disease: UBI Study.J Nephrol. 32: 989-1001Crossref (80) 4Raphael Isakova T. Ix J.H. al.A randomized trial comparing safety, adherence, and pharmacodynamics profiles two doses CKD: BASE Pilot Trial.J Am Soc 2020; 31: 161-174Crossref (26) Scholar or prevent recurrence stone disease.5Pak C.Y. Britton F. Peterson R. al.Ambulatory evaluation nephrolithiasis. Classification, clinical presentation diagnostic criteria.Am J Med. 1980; 69: 19-30Abstract Scholar,6Pak Sakhaee K. Fuller C. Successful management uric nephrolithiasis potassium citrate.Kidney 1986; 30: 422-428Abstract Proper dosing alkali necessary to avoid complications such alkalosis excessive urine alkalinization, which can lead calcium phosphate stones. There evidence that women excrete more alkaline than men, this tendency account higher prevalence stones women.7Goldfarb D.S. A woman recurrent stones.Clin 2012; 7: 1172-1178Crossref (35) Worcester al reported because they extract dietary men.8Worcester E.M. Bergsland K.J. Gillen D.L. Coe F.L. Mechanism pH normal compared men.Am Physiol Renal Physiol. 2018; 314: F623-F629Crossref (30) If these findings could be extrapolated practice, need prescribed lower salts lest their becomes too alkaline. To our knowledge, no studies have directly addressed whether should dosed differently between men. investigate sex differences response treatment, we examined changes amount ammonium (NH4+) weight-based (NaHCO3) men good health those CKD. The study was approved by institutional review board Stanford University, volunteers provided written informed consent. Trial boards at each site participants registered clinicaltrials.gov (NCT02521181). In healthy volunteers, age-matched (8 7 men) median age 34.3 years (interquartile range, 5.7) received single daily dose NaHCO3 0.5 mEq/kg body weight 1 week (Table S1). Participants were asked complete 24-hour sample collection baseline after taking dosage while consuming similar free-choice diet. Baseline pH, NH4+, levels not significantly different After administration week, increased NH4+ level decreased entire cohort. We noted change from output parameters treatment 1).Table 1Baseline post-NaHCO3 (NH4+), citrate/creatinine diseaseHealthy VolunteersBaselinePost-NaHCO3pHNH4+ (mmol)Citrate/Cr (mg/mg)pHNH4+ (mg/mg)Total (n=15)6.56 (0.67)32.4 (9.80)0.466 (0.131)7.23 (0.47)aP value <0.05 comparison NaHCO3.22.0 (8.34)aP NaHCO3.0.549 (0.217)Women (n=8)6.63 (0.71)29.4 (8.08)0.524 (0.129)7.33 (0.43)aP NaHCO3.17.0 (6.27)aP NaHCO3.0.703 (0.254)Men (n=7)6.49 (0.67)35.8 (11.1)0.400 (0.104)7.17 (0.51)25.6 (8.10)0.440 (0.098)P W vs. MbP comparisons same visit.0.700.230.060.580.070.08P difference mean McP men.———0.990.840.19BASE ParticipantsBaselinePost-NaHCO3pHNH4+ (n=123) LD-NaHCO3 (n=47)5.86 (0.46)19.8 (10.8)0.195 (0.166)6.61 (0.55)aP NaHCO3.13.5 (8.1)aP NaHCO3.0.284 (0.182)aP NaHCO3. HD-NaHCO3 (n=76)5.75 (0.46)22.7 (12.9)0.151 (0.137)6.73 (0.56)aP NaHCO3.13.1 (9.4)aP NaHCO3.0.262 (0.172)aP NaHCO3.Women (n=16)5.96 (0.50)17.7 (10.4)0.243 (0.195)6.65 (0.61)aP NaHCO3.10.7 (3.7)aP NaHCO3.0.386 (0.257) (n=21)5.80 (0.49)19.1 (10.8)0.177 (0.157)6.79 NaHCO3.11.1 NaHCO3.0.302 (0.132)aP NaHCO3.Men (n=31)5.79 (0.42)20.9 (11.0)0.170 (0.147)6.58 (0.53)aP NaHCO3.14.9 (9.3)aP NaHCO3.0.235 (0.106)aP (n=55)5.73 (0.45)24.1 (13.5)0.141 (0.128)6.70 NaHCO3.13.9 (9.8)aP NaHCO3.0.248 (0.183)aP NaHCO3.P visit. LD-NaHCO30.200.330.200.660.030.04 HD-NaHCO30.540.100.360.540.220.17P LD-NaHCO30.700.330.20 HD-NaHCO3———0.890.360.83Note: Values (SD); values are average 12 28 visit Trial.Abbreviations: Cr, creatinine; HD, high dose; LD, low ammonium; NaHCO3, bicarbonate; potential hydrogen; W, women; M, men.a P NaHCO3.b visit.c Open table new tab Note: Trial. Abbreviations: next stage 3 4 CKD Trial4Raphael S2). either lean per day (LD-NaHCO3) 0.8 (HD-NaHCO3) divided weeks. given any specific instructions other intake discretion. Trial, measured samples part protocol; therefore, report random compare volunteers. LD-NaHCO3, cohort HD-NaHCO3, cohort, again found 1, Tables S3 S4). Our data demonstrate if persons an ad libitum regimen will raise extent particularly important hypocitraturia.7Goldfarb has several limitations. First, size small, it possible trend toward (after NaHCO3) would reached statistical significance larger size. Second, although included CKD, did include disease. Therefore, do know induce equivalent recurrence. Third, respond effects on balance quantitative measures net endogenous production excretion. conclusion, pharmacodynamic alkalis, suggesting person’s play major factor determining initial alkali. Research idea design: AP, KR; acquisition: SS, analysis/interpretation: JL, KR, SRS, CG, SC, PF; analysis: SK; supervision mentorship: AC, JI, TI, MW, DR, SMS, LF, JG. Each author contributed intellectual content during article drafting revision accepts accountability overall work ensuring questions pertaining accuracy integrity portion appropriately investigated resolved. This funded School Medicine Women’s Health Sex Differences Center. conducted National Institute Diabetes Digestive Kidney Diseases Clinical Trials Chronic Disease Consortium (contracts U01DK097093, U01DK099877, U01DK099924, U01DK099930, U01DK099933). funders had role design, collection, analysis, interpretation data, writing decision submit publication. Dr reports consulting honorarium Blueprint Partnership Manchester Ltd. remaining authors declare relevant financial interests. Received January 16, 2023 submission expedited consideration track external peer reviews. Direct editorial input Statistical Editor Editor-in-Chief. Accepted revised form March 11, 2023. Download .pdf (.17 MB) Help pdf files Supplementary File (PDF)Table S1-S4.