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Am J Physiol Renal Physiol. 2019 Jun 19. doi: 10.1152/ajprenal.00044.2019. [Epub ahead of print]

Urine citrate excretion identifies changes in acid retention as eGFR declines in patients with chronic kidney disease.

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Internal Medicine, Baylor Scott and White Health.
Surgery, Texas Tech University HSC, United States.
Biostatistics, Baylor Scott and White Health.
Biostatistics, Baylor Scott and White Health and Wellness Center, United States.
St. Elizabeth's.
Internal Medicine, Baylor Scott and White Health, United States.


We examined as secondary analysis if increased acid (H+) retention occurring as eGFR decreases in patients with chronic kidney disease (CKD) stage 2 eGFR (60-89 ml.min-1.73m-2) (CKD 2) without metabolic acidosis and followed over ten years is predicted by changes in 8 hour urine citrate excretion (UcitrateV). We randomized 120 CKD 2 non-diabetic, hypertension-associated nephropathy patients with plasma total CO2 (PTCO2) > 24 mM to receive 0.5 mEq/kg bw/day NaHCO3 (HCO3-, n=40), 0.5 mEq/kg bw/day NaCl (NaCl, n=40), or Usual Care (UC, n=40). We assessed eGFR (CKD-EPI) and H+ retention by comparing observed to expected PTCO2 increase 2 hours after oral NaHCO3 bolus (0.5 mEq/kg bw). Although 10-year vs. baseline eGFR was lower for each group, 10-year eGFR was higher (p<0.01) in HCO3- (59.6±4.8 ml.min-1.73m-2) than NaCl and UC (52.1±5.9 and 52.3±4.1 ml.min-1.73m-2, respectively). Less eGFR preservation was associated with higher 10-year vs. baseline H+ retention in NaCl (26.5±13.1 vs. 18.2±15.3 mmol, p<0.01) and UC (24.8±11.3 vs. 17.7±10.9 mmol, p<0.01) and with lower 10-year vs. baseline UcitrateV for NaCl (162±47 vs. 196±52 mg, respectively, p<0.01) and UC (153±41 vs. 186±42 mg, respectively, p<0.01). Conversely, better eGFR preservation in HCO3- was associated with no differences in 10-year vs. baseline H+ retention (14.2±13.5 vs. 16.1±15.1 mmol, p=1.00) or UcitrateV (212±45 vs. 203±49 mg, respectively, p=0.74). An overall generalized linear model for repeated measures showed that UcitrateV predicted H+ retention (p<0.01). Less eGFR preservation in CKD 2 patients without metabolic acidosis was associated with increased H+ retention that was predicted by decreased UcitrateV.


acid retention; acidosis; bicarbonate; chronic kidney disease; glomerular filtration rate

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