Serum Bicarbonate Levels and the Progression of Kidney Disease: A Cohort Study

Abstract

Background Animal models of kidney disease have linked metabolic acidosis with renal damage. The role of low serum bicarbonate levels in kidney disease progression in humans has not been studied. Study Design Retrospective cohort study. Setting & Participants: Adults visiting a medical clinic in the Bronx, NY from 01/01/01 to 12/31/03 were included in the study (n=5,422) and followed until 6/30/07 Predictor Serum bicarbonate levels Outcomes Kidney disease progression was defined as either a decline in the estimated glomerular filtration rate (eGFR) by 50% or reaching an eGFR of <15 ml/min/1.73m2 (n=337). Measurements Patients’ baseline demographics, comorbidities, laboratory data and socioeconomic status were recorded. Serial outpatient serum creatinines were collected (median, 5 measurements/ person). Results The mean age was 52 years, 69% were women, 45% were African-American, 31% were Hispanic, 21% had diabetes mellitus, 41% had hypertension, and 9% had a baseline eGFR <60 ml/min/1.73m2. Kidney disease progressed by the definition above in 337 patients (6.2%). Compared to the reference group (bicarbonate level 25-26 mEq/L), the hazard ratio for progression after adjustment for potential confounders was 1.54 (95% CI 1.13-2.09) for bicarbonate levels ≤22 mEq/L, 0.97 (95% CI 0.70-1.35) for levels 23-24 mEq/L and 1.14 (95% CI 0.84-1.55) for levels ≥27 mEq/L. (Global p-value for inclusion of serum bicarbonate in the model, 0.01). These results remained similar when using different definitions of the outcome (an eGFR decline by 30%, 1288 outcomes (24%)) or doubling of serum creatinine (268 outcomes (4.9%)). Limitations Data used in study was collected for clinical, not research, purposes. Conclusions Low serum bicarbonate is associated with the progression of kidney disease, independent of baseline eGFR and other clinical, demographic and socioeconomic factors. Prospective studies are needed to confirm this relationship and to evaluate the efficacy of alkali supplements for slowing progression.

High Dietary Acid Load Predicts ESRD among Adults with CKD

“…They reinforce the findings of earlier studies that have shown beneficial effects of alkali supplementation in slowing the progression of kidney disease 7,8 and studies documenting the association of metabolic acidosis with CKD progression. 15,16 We noted an association of DAL and progression to ESRD for participants with albuminuria. Our findings are in accordance with previous studies that have shown high consumption of meat food groups (i.e., each serving per day greater intake of the sum of red meat, processed meat, poultry, and fish) to be positively associated with albuminuria.…”

Fractional Excretion of Phosphorus Modifies the Association between Fibroblast Growth Factor-23 and Outcomes

“…Low serum bicarbonate concentrations have been identified as a marker of CKD progression independent of eGFR. 20 Similarly, neutrophil gelatinaseassociated lipocalin, a marker of kidney tubule cell damage originally identified in AKI studies, 21 has been associated with interstitial fibrosis and tubular atrophy in renal biopsies in community-living patients with CKD. 22 Moreover, higher urine neutrophil gelatinase-associated lipocalin concentrations were recently associated with incident development of CKD in community-living individuals without AKI.…”

Dietary Acid, Age, and Serum Bicarbonate Levels among Adults in the United States

“…Even among individuals without kidney disease, a lowgrade acidosis contributes to bone breakdown and possibly loss of muscle mass (9,10), and low-normal serum bicarbonate levels have been associated with lesser muscle strength and cardiovascular fitness, greater insulin resistance, and faster progression of kidney disease (6,7,13,26). Interventions to treat acidosis, including dietary modifications (27,28), may be most efficacious among older persons, in whom the capacity to excrete the daily acid load from modern Western diets is diminished.…”