Low Serum Bicarbonate and Kidney Function Decline: The Multi-Ethnic Study of Atherosclerosis (MESA)

BackgroundAmong populations with established chronic kidney disease (CKD), metabolic acidosis is associated with more rapid progression of kidney disease. The association of serum bicarbonate concentrations with early declines in kidney function is less clear.Study designRetrospective cohort study.Setting & participants5,810 participants in the Multi-Ethnic Study of Atherosclerosis (MESA) with a baseline estimated glomerular filtration rate (eGFR) > 60mL/min/1.73 m(2) using the CKD-EPI (CKD Epidemiology Collaboration) creatinine-cystatin C equation.PredictorsSerum bicarbonate concentrations.OutcomesRapid kidney function decline (eGFR decline > 5% per year) and incident reduced eGFR (eGFR < 60mL/min/1.73 m(2) with minimum rate of eGFR loss of 1 mL/min/1.73 m(2) per year).ResultsAverage bicarbonate concentration was 23.2 ± 1.8mEq/L. 1,730 (33%) participants had rapid kidney function decline, and 487 had incident reduced eGFR during follow-up. Each 1-SD lower baseline bicarbonate concentration was associated with 12% higher adjusted odds of rapid kidney function decline (95% CI, 6%-20%) and higher risk of incident reduced eGFR (adjusted incidence rate ratio, 1.11; 95% CI, 1.03-1.20) in models adjusting for demographics, baseline eGFR, albuminuria, and CKD risk factors. The OR for the associations of bicarbonate level < 21 mEq/L relative to 23-24 mEq/L was 1.35 (95% CI, 1.05-1.73) for rapid kidney function decline, and the incidence rate ratio was 1.16 (95% CI, 0.83-1.62) for incident reduced eGFR.LimitationsCause of metabolic acidosis cannot be determined in this study.ConclusionsLower serum bicarbonate concentrations are associated independently with rapid kidney function decline independent of eGFR or albuminuria in community-living persons with baseline eGFR > 60 mL/min/1.73 m(2). If confirmed, our findings suggest that metabolic acidosis may indicate either early kidney disease that is not captured by eGFR or albuminuria or may have a causal role in the development of eGFR < 60 mL/min/1.73 m(2)

Low Serum Bicarbonate and Kidney Function Decline: The Multi-Ethnic Study of Atherosclerosis (MESA)

BACKGROUND: Among populations with established chronic kidney disease (CKD), metabolic acidosis is associated with more rapid progression of kidney disease. The association of serum bicarbonate concentrations with early declines in kidney function is less clear. STUDY DESIGN: Retrospective cohort study. SETTING & PARTICIPANTS: 6380 participants in the Multi-Ethnic Study of Atherosclerosis (MESA) with a baseline estimated glomerular filtration rate (eGFR) >60 mL/min/1.73m(2) using the CKD-EPI (CKD Epidemiology Collaboration) creatinine–cystatin C equation. PREDICTORS: Serum bicarbonate concentrations. OUTCOMES: Rapid kidney function decline (eGFR decline >5% per year) and incident reduced eGFR (eGFR<60 mL/min/1.73 m(2) with minimum rate of eGFR loss of 1 mL/min/1.73 m(2) per year). RESULTS: The average bicarbonate concentration was 23.2 ± 1.8 mEq/L. 1730 (33%) participants had rapid kidney function decline, and 487 had incident reduced eGFR during follow-up. Each 1-SD lower baseline bicarbonate concentration was associated with 12% higher adjusted odds of rapid kidney function decline (95% CI, 6%–20%) and higher risk of incident reduced eGFR (adjusted incidence rate ratio, 1.11; 95% CI, 1.03–1.20) in models adjusting for demographics, baseline eGFR, albuminuria, and CKD risk factors. The OR for the associations of bicarbonate <21mEq/L relative to 23–24 mEq/L was 1.35 (95% CI, 1.05–1.73) for rapid kidney function decline, and the incidence rate ratio was 1.16 (95% CI, 0.83–1.62) for incident reduced eGFR. LIMITATIONS: Etiology of metabolic acidosis cannot be determined in this study. CONCLUSIONS: Lower serum bicarbonate concentrations are independently associated with rapid kidney function decline independent of eGFR or albuminuria in community-living persons with a baseline eGFR >60 mL/min/1.73 m(2). If confirmed, our findings suggest that metabolic acidosis may indicate either early kidney disease that is not captured by eGFR or albuminuria, or may have a causal role in the development of an eGFR <60 mL/min/1.73 m(2)

Serum Bicarbonate Concentrations and Kidney Disease Progression in Community-Living Elders: The Health, Aging, and Body Composition (Health ABC) Study

BackgroundIn populations with prevalent chronic kidney disease (CKD), lower serum bicarbonate levels are associated with more rapid CKD progression, but whether lower bicarbonate levels also are associated with risk of incident estimated glomerular filtration rate (eGFR) &lt; 60 mL/min/1.73 m(2) and CKD progression among community-living persons with predominantly preserved kidney function is unknown.Study designLongitudinal observational cohort study.Setting &amp; participantsWell-functioning community-living elders aged 70-79 years at inception.PredictorSerum bicarbonate level measured at the time of collection by arterialized venous blood sample using an arterial blood gas analyzer.OutcomesChange in eGFR over 7 years, and new eGFR &lt; 60 mL/min/1.73 m(2) with a rate of loss of at least 1 mL/min/1.73 m(2) per year.MeasurementsLinear and logistic regressions were used to evaluate associations of baseline serum bicarbonate level with change in eGFR and incident eGFR &lt; 60 mL/min/1.73 m(2).ResultsAt baseline, mean eGFR was 84 ± 16 (SD)mL/min/1.73 m(2), and serum bicarbonate level was 25.2 ± 1.9 mmol/L. Compared with participants with higher bicarbonate concentrations (23.0-28.0 mmol/L), those with bicarbonate concentrations &lt; 23 mmol/L (n = 85 [8%]) lost eGFR0.55 (95% CI, 0.13-0.97) mL/min/1.73 m(2) per year faster in models adjusted for demographics, CKD risk factors, baseline eGFR, and urine albumin-creatinine ratio. Among the 989 (92%) participants with baseline eGFRs &gt; 60 mL/min/1.73 m(2), 252 (25%) developed incident eGFRs &lt; 60 mL/min/1.73 m(2) at follow-up. Adjusting for the same covariates, participants with bicarbonate concentrations &lt; 23 mmol/L had nearly 2-fold greater odds of incident eGFRs &lt; 60 mL/min/1.73 m(2) (OR, 1.72; 95% CI, 0.97-3.07) compared with those with higher bicarbonate concentrations.LimitationsOnly 2 measurements of kidney function separated by 7 years and loss to follow-up due to intervening mortality in this elderly population.ConclusionsLower serum bicarbonate concentrations are associated independently with decline in eGFR and incident eGFR &lt; 60 mL/min/1.73 m(2) in community-living older persons. If confirmed, serum bicarbonate levels may give insight into kidney tubule health in persons with preserved eGFRs and suggest a possible new target for intervention to prevent CKD development

Serum Bicarbonate Concentrations and Kidney Disease Progression in Community-Living Elders: The Health, Aging, and Body Composition (Health ABC) Study

BACKGROUND: In populations with prevalent chronic kidney disease (CKD), lower serum bicarbonate is associated with more rapid CKD progression, but whether lower bicarbonate is also associated with risk of incident estimated glomerular filtration rate (eGFR) <60 mL/min/1.73m(2) and progression among community-living persons with predominantly preserved kidney function is unknown. STUDY DESIGN: Longitudinal observational cohort study. SETTING & PARTICIPANTS: Well functioning community living elders aged 70–79 years at inception. PREDICTOR: Serum bicarbonate measured at the time of collection by arterialized venous blood sample using an arterial blood gas analyzer. OUTCOMES: Change in eGFR, and new eGFR < 60 ml/min/1.73m(2) and loss of ≥1 ml/min/1.73m(2) per year at follow-up. MEASUREMENTS: Linear and logistic regressions were used to evaluate associations of baseline serum bicarbonate with change in eGFR and incident eGFR <60 mL/min/1.73m(2). RESULTS: At baseline, mean eGFR was 84±16 (SD) mL/min/1.73m(2), and serum bicarbonate was 25.2±1.9 mmol/L. Compared to participants with higher bicarbonate concentrations (23.0–28.0 mmol/L), those with bicarbonate concentrations < 23 mmol/L (n=85 [8%]) lost eGFR 0.55 (95%CI, 0.13–0.97) mL/min/1.73m(2) per year faster in models adjusted for demographics, CKD risk factors, baseline eGFR, and urine albumin-creatinine ratio. Among the 989 (92%) participants with baseline eGFR>60 mL/min/1.73m(2), 252 (25%) developed incident eGFR <60 mL/min/1.73m(2) at follow-up. Adjusting for the same covariates, participants with bicarbonate concentrations < 23 mmol/L had nearly 2-fold greater odds of incident eGFR <60 mL/min/1.73m(2) (OR, 1.72; 95% CI, 0.97–3.07) compared to those with higher bicarbonate concentrations. LIMITATIONS: Only two measurements of kidney function separated by seven years and loss to follow up due to intervening mortality in this elderly population. CONCLUSIONS: Lower serum bicarbonate concentrations are independently associated with decline in eGFR and incident eGFR <60 mL/min/1.73m(2) in community-living older persons. If confirmed, serum bicarbonate levels may give insights into kidney tubule health among persons with preserved eGFR and suggest a possible new target for intervention to prevent CKD development

Abatacept in children with juvenile idiopathic arthritis: a randomised, double-blind, placebo-controlled withdrawal trial

Background Some children with juvenile idiopathic arthritis either do not respond, or are intolerant to, treatment with disease-modifying antirheumatic drugs, including anti-tumour necrosis factor (TNF) drugs. We aimed to assess the safety and efficacy of abatacept, a selective T-cell costimulation modulator, in children with juvenile idiopathic arthritis who had failed previous treatments.Methods We did a double-blind, randomised controlled withdrawal trial between February, 2004, and June, 2006. We enrolled 190 patients aged 6-17 years, from 45 centres, who had a history of active juvenile idiopathic arthritis; at least five active joints; and an inadequate response to, or intolerance to, at least one disease-modifying antirheumatic drug. All 190 patients were given 10 mg/kg of abatacept intravenously in the open-label period of 4 months. of the 170 patients who completed this lead-in course, 47 did not respond to the treatment according to predefined American College of Rheumatology (ACR) paediatric criteria and were excluded. of the patients who did respond to abatacept, arthritis, and 62 were randomly assigned to receive placebo at the same dose and timing. The primary endpoint was time to flare of arthritis. Flare was defined as worsening of 30% or more in at least three of six core variables, with at least 30% improvement in no more than one variable. We analysed all patients who were treated as per protocol. This trial is registered, number NCT00095173.Findings Flares of arthritis occurred in 33 of 62 (53%) patients who were given placebo and 12 of 60 (20%) abatacept patients during the double-blind treatment (p=0.0003). Median time to flare of arthritis was 6 months for patients given placebo (insufficient events to calculate IQR); insufficient events had occurred in the abatacept group for median time to flare to be assessed (p=0.0002). The risk of flare in patients who contined abatacept was less than a third of that for controls during that double-blind period (hazard ratio 0.31, 95% CI 0.16-0.95). During the double-blind period, the frequency of adverse events did not differ in the two treatment groups, Adverse events were recorded in 37 abatacept recipients (62%) and 34 (55%) placebo recipients (p=0.47); only two serious adverse events were reported, bouth in controls (p=0.50).Interpretation Selective modulation of T-cell costimulation with abatacept is a rational alternative treatment for children with juvenile idiopathic arthritis.Funding Bristol-Myers Squibb