TY - JOUR
T1 - Spot urinary citrate-to-creatinine ratio is a marker for acid-base status in chronic kidney disease
AU - Gianella, Fabiola G.
AU - Prado, Victor E.
AU - Poindexter, John R.
AU - Adams-Huet, Beverley
AU - Li, Xilong
AU - Miller, R. Tyler
AU - Sakhaee, Khashayar
AU - Maalouf, Naim M.
AU - Moe, Orson W.
N1 - Funding Information:
The authors are indebted to Dr. Henry Quiñones, and Dr. Kamal Sambandam’s assistance to enable us to recruit from the Parkland glomerulonephritis and CKD clinics, the staff at the Clinical Chemistry Laboratory at the Charles and Jane Pak Center for Mineral Metabolism and Clinical Research. This work was supported by the O’Brien Kidney Research Center (Grant P30-DK079328, to OWM), the Pak-Seldin Center for Metabolic Research, and the National Institutes of Health (Grants R01 DK081423 , to KS and OWM and R01 DK091392, to OWM).
Funding Information:
The authors are indebted to Dr. Henry Qui?ones, and Dr. Kamal Sambandam's assistance to enable us to recruit from the Parkland glomerulonephritis and CKD clinics, the staff at the Clinical Chemistry Laboratory at the Charles and Jane Pak Center for Mineral Metabolism and Clinical Research. This work was supported by the O'Brien Kidney Research Center (Grant P30-DK079328, to OWM), the Pak-Seldin Center for Metabolic Research, and the National Institutes of Health (Grants R01 DK081423, to KS and OWM and R01 DK091392, to OWM).
Publisher Copyright:
© 2020 International Society of Nephrology
PY - 2021/1
Y1 - 2021/1
N2 - Due to multiple compensating mechanisms, the serum bicarbonate concentration is a relatively insensitive marker of acid-base status; especially in chronic kidney disease (CKD). This is a major drawback that impairs the ability to diagnose acid excess or monitor alkali therapy. We postulated that it is more logical to measure the compensatory defense mechanism(s) rather than the defended parameter, which remains normal if the compensation is successful. Therefore, a retrospective cross-sectional study was performed in 1733 stone formers along with a prospective cross-sectional study of 22 individuals with normal kidney function and 50 patients in different stages of CKD. While serum bicarbonate was flat and did not fall below the reference range until near CKD stage 5, citrate excretion (24-hour urinary citrate excretion rate; urinary citrate-to-creatinine ratio, in the retrospective analysis, and spot urinary citrate-to-creatinine ratio in the prospective study) progressively and significantly declined starting from CKD stage 2. Following an acute acid load in 25 participants with a wide range of estimated glomerular filtration rates, the urinary citrate-to-creatinine ratio inversely and significantly associated with acid accumulation, whereas serum bicarbonate did not. We compared changes in serum bicarbonate and urinary citrate-to-creatinine ratio in response to alkali therapy in patients with CKD stage 3 or 4 started on potassium citrate in our kidney stone database. With alkali therapy, there was no change in serum bicarbonate, but the urinary citrate-to-creatinine ratio rose consistently in all patients adherent to potassium citrate therapy. Thus, the urinary citrate-to-creatinine ratio (the defense mechanism) is a potential easily implementable, pragmatic, and a superior parameter to serum bicarbonate (the defended entity) to assess acid-base status, and monitor alkali therapy. Additional studies are needed before a clinical test can be devised.
AB - Due to multiple compensating mechanisms, the serum bicarbonate concentration is a relatively insensitive marker of acid-base status; especially in chronic kidney disease (CKD). This is a major drawback that impairs the ability to diagnose acid excess or monitor alkali therapy. We postulated that it is more logical to measure the compensatory defense mechanism(s) rather than the defended parameter, which remains normal if the compensation is successful. Therefore, a retrospective cross-sectional study was performed in 1733 stone formers along with a prospective cross-sectional study of 22 individuals with normal kidney function and 50 patients in different stages of CKD. While serum bicarbonate was flat and did not fall below the reference range until near CKD stage 5, citrate excretion (24-hour urinary citrate excretion rate; urinary citrate-to-creatinine ratio, in the retrospective analysis, and spot urinary citrate-to-creatinine ratio in the prospective study) progressively and significantly declined starting from CKD stage 2. Following an acute acid load in 25 participants with a wide range of estimated glomerular filtration rates, the urinary citrate-to-creatinine ratio inversely and significantly associated with acid accumulation, whereas serum bicarbonate did not. We compared changes in serum bicarbonate and urinary citrate-to-creatinine ratio in response to alkali therapy in patients with CKD stage 3 or 4 started on potassium citrate in our kidney stone database. With alkali therapy, there was no change in serum bicarbonate, but the urinary citrate-to-creatinine ratio rose consistently in all patients adherent to potassium citrate therapy. Thus, the urinary citrate-to-creatinine ratio (the defense mechanism) is a potential easily implementable, pragmatic, and a superior parameter to serum bicarbonate (the defended entity) to assess acid-base status, and monitor alkali therapy. Additional studies are needed before a clinical test can be devised.
KW - acid-base status
KW - alkali
KW - bicarbonate
KW - chronic kidney disease
KW - citrate
UR - http://www.scopus.com/inward/record.url?scp=85097752859&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85097752859&partnerID=8YFLogxK
U2 - 10.1016/j.kint.2020.07.006
DO - 10.1016/j.kint.2020.07.006
M3 - Article
C2 - 32721446
AN - SCOPUS:85097752859
SN - 0085-2538
VL - 99
SP - 208
EP - 217
JO - Kidney international
JF - Kidney international
IS - 1
ER -