Higher serum bicarbonate levels within the normal range are associated with better survival and renal outcomes in African Americans

Abstract

Recent studies suggest that correcting low serum bicarbonate levels may reduce the progression of kidney disease; however, few patients with chronic kidney disease have low serum bicarbonate. Therefore, we examined whether higher levels of serum bicarbonate within the normal range (20-30 mmol/l) were associated with better kidney outcomes in the African American Study of Kidney Disease and Hypertension (AASK) trial. At baseline and during follow-up of 1094 patients, the glomerular filtration rates (GFR) were measured by iothalamate clearances and events were adjudicated by the outcomes committee. Mean baseline serum bicarbonate, measured GFR, and proteinuria were 25.1 mmol/l, 46 ml/min per 1.73 m(2), and 326 mg/g of creatinine, respectively. Each 1 mmol/l increase in serum bicarbonate within the normal range was associated with reduced risk of death, dialysis, or GFR event and with dialysis or GFR event (hazard ratios of 0.942 and 0.932, respectively) in separate multivariable Cox regression models that included errors-in-variables calibration. Cubic spline regression showed that the lowest risk of GFR event or dialysis was found at serum bicarbonate levels near 28-30 mmol/l. Thus, our study suggests that serum bicarbonate is an independent predictor of CKD progression. Whether increasing serum bicarbonate into the high-normal range will improve kidney outcomes during interventional studies will need to be considered.

Figure 1. Probability of death or renal composite (dialysis or glomerular filtration rate (GFR) event) according to baseline serum bicarbonate levels

Participants were categorized into four groups according to the baseline bicarbonate levels (<20 mmol/l, 20.0–24.9 mmol/l, 25.0–29.9 mmol/l, and ≥30 mmol/l). The unadjusted results are shown here.

Figure 2. Restricted cubic spline regression model of the hazard of glomerular filtration rate (GFR) event, dialysis, or death among all participants by baseline serum bicarbonate levels after adjusting for gender, age, trial assignment, measured GFR, and proteinuria

The estimated adjusted hazard ratio as a function of baseline serum bicarbonate, using a bicarbonate level of 20 mmol/l as the reference, with 95% pointwise confidence limits, is shown here.

Figure 3. Probability of the renal composite (dialysis or glomerular filtration rate (GFR) event) according to baseline serum bicarbonate levels

Participants were categorized into four groups according to the baseline bicarbonate levels (<20 mmol/l, 20.0–24.9 mmol/l, 25.0–29.9 mmol/l, and ≥30 mmol/l). The unadjusted results are shown here.

Figure 4. Restricted cubic spline regression model of the hazard of glomerular filtration rate (GFR) event or dialysis among all participants by baseline serum bicarbonate levels after adjusting for gender, age, trial assignment, measured GFR, and proteinuria

The estimated adjusted hazard ratio as a function of baseline serum bicarbonate, using a bicarbonate level of 20 mmol/l as the reference, with 95% pointwise confidence limits, is shown here.