Is Metabolic Acidosis a Novel Risk Factor for a Long-Term Graft Survival in Patients after Kidney Transplantation?

Abstract

<b><i>Background:</i></b> Results of both experimental and clinical studies suggest that metabolic acidosis (MA) contributes to the progression of chronic kidney disease (CKD) and mortality in CKD patients. It is unknown whether the same relationship exists in kidney transplantation (KTx) patients. The aim of this observational study was to examine this relationship between MA and both mortality and renal outcomes in patients after KTx. <b><i>Methods:</i></b> Four hundred eighty-six (290 male; 196 female) patients aged 48 ± 12 years, at least 1 year after KTx, were analyzed. Blood HCO<sub>3</sub><sup>–</sup> was measured, and patients were then observed over 3 years. MA was defined as the blood HCO<sub>3</sub><sup>–</sup> concentration <22 mmol/L. The end points of survival analysis were death and initiation of dialysis therapy. In patients who did not reach the above-mentioned end points, the difference between final (after 3 years of follow-up) and initial estimated glomerular filtration rate (eGFR) was calculated. <b><i>Results:</i></b> MA was initially diagnosed in 57 (12%) patients after KTx. Three-year patient survival was 89.5% in the MA group and 97.4% in the non-MA group (<i>p</i> = 0.001). Three-year graft survival was 73.7% for patients with MA and 93.0% for patients without MA (<i>p</i> < 0.001). In patients with MA who did not reach study end points, blood bicarbonate concentration at baseline correlated positively with a change in eGFR (<i>R</i> = 0.48, <i>p</i> = 0.002, <i>n</i> = 36). Such a correlation was not found in patients without MA (<i>n</i> = 388). <b><i>Conclusions:</i></b> (1) MA significantly increases the risk of mortality in patients after KTx. (2) The intensity of MA may be associated with progression of transplanted kidney dysfunction in KTx patients.

Metabolic Acidosis in Patients with CKD: Epidemiology, Pathogenesis, and Treatment

“…In patients with metabolic acidosis, the risk of death or the initiation of renal replacement therapy was significantly several times higher than in patients without metabolic acidosis (RR = 4.11 and RR = 3.58, respectively). In addition, in patients after kidney transplantation with metabolic acidosis, the concentration of bicarbonate in the blood at the beginning of the observation showed a positive correlation with the change in eGFR value during 3 years of observation [56].…”

“…In the observational 4C study, Harambat et al [13] showed that in children and adolescents with CKD and serum bicarbonate concentration <18 mmol/L, the risk of eGFR reduction by >50% or achieving eGFR below 10 mL/min/1.73 m 2 or initiating renal replacement therapy was 2.4 times higher compared to patients with serum bicarbonate concentrations >18 mmol/L. Gojowy et al [56] in a 3-year prospective observational study assessed the effect of blood bicarbonate concentration in kidney transplant patients on the risk of death or dialysis initiation. In patients with metabolic acidosis, the risk of death or the initiation of renal replacement therapy was significantly several times higher than in patients without metabolic acidosis (RR = 4.11 and RR = 3.58, respectively).…”

A Pilot Study of the Safety and Efficacy of Alkali Therapy on Vascular Function in Kidney Transplant Recipients

“…Serum bicarbonate levels <24 mEq/L have been found to be a significant risk factor for graft failure, cardiovascular events, and mortality in J o u r n a l P r e -p r o o f KTRs. 14,[18][19][20][21] This suggests that KTRs may benefit from alkali therapy to correct the acid retention.…”

“…[15][16][17] Transplant recipients with lower serum bicarbonate levels have an increased risk of graft loss, cardiovascular events and mortality. 14,[18][19][20][21] Several small interventional trials have shown that bicarbonate administration slows the rate of kidney disease progression, even in individuals with normal serum bicarbonate levels. [22][23][24] Additionally, a prior pilot study of 20 participants with chronic kidney disease (CKD) stage 3-4 with metabolic acidosis (mean (SD) serum bicarbonate level 19.5 ± 2.3 mEq/L) found that bicarbonate administration resulted in improved vascular endothelial function as measured by brachial-artery flow-mediated dilation (FMD).…”

Thinking Outside the Box: Novel Kidney Protective Strategies in Kidney Transplantation

“…In one multicenter, retrospective cohort study of 2318 adult kidney transplant recipients, serum bicarbonate <22 mEq/L at 3 months was associated with a 74% higher risk of allograft loss (hazard ratio, 1.74; 95% CI, 1.26 to 2.42) (38). More recently, Gojowy et al (42) showed that metabolic acidosis was present in 12% of 486 recipients and that those with HCO 3 <22 mEq/L had a 3-year graft survival of 74% compared with 93% for those without metabolic acidosis after adjusting for baseline eGFR. The Preserve-Transplant study is an ongoing prospective, single-blind, multicenter, randomized controlled trial of sodium bicarbonate versus placebo in 240 kidney transplant recipients (43).…”