Posttransplant Care: Don’t Forget Bicarbonate!

Abstract

The medical management of patients with a renal allograft is intricate and typically involves management of complex immunosuppressive regimens, hypertension, hyperlipidemia, hyperglycemia, and treatment or prophylaxis of viral or bacterial infections. Derangements of bone and mineral metabolism typically persist late into the posttransplant period, in particular hypophosphatemia, with or without concomitant hyperparathyroidism. Supplementation with phosphate is common; in addition, calcium and biphosphonate are frequently necessary because of the routine use of steroids with associated bone loss. With progressive allograft nephropathy, new challenges arise that require special attention and treatment. It is therefore perhaps not surprising that relatively little attention has been given to acid-base homeostasis in the posttransplant period. The causes of metabolic acidosis in this setting are multifactorial but may include calcineurin– inhibitor-induced tubular dysfunction, reduced glomerular filtration rate with impaired renal clearance of acid, and systemic phosphate depletion. It is typically a combination of anion-gap and nonanion-gap (hyperchloremic) metabolic acidosisthatprogresseswithfurtherdeclineinrenalfunction. Is chronic metabolic acidosis detrimental to the health of our patients, or is it simply a laboratory value that deserves little attention? An early contribution to this topic was in the pediatric literature: McSherry et al. (1) demonstrated that alkali therapy in children with renal tubular acidosis led to accelerated growth and attainment of normal stature. A host of more recent literature emphasizes the detrimental effects inadultpatients,includingnegativeproteinbalancewithloss of lean body mass, negative calcium and phosphorus balance with bone mineral loss, hypoalbuminemia, inflammation, and complex endocrine derangements of the growth hormone/insulin-like growth factor-1 and thyroid hormone axis.Thisledtopublicationofguidelinesonthemanagement of metabolic acidosis by the National Kidney Foundation (NKF) in the United States. Initial recommendations in 2001 addressed specifically hemodialysis patients, suggesting a “stabilized” serum bicarbonate level of at least 22 mmol/L, which was expanded in 2003 to include chronic kidney disease (CKD) stages 3, 4, and 5 for the same target bicarbonate level, with alkali supplementation when necessary (2). Solid evidence for these guidelines is lacking, rather, the NKF guidelines rely on extrapolations from typically non-randomized trials in hemodialysis patients, and on expert opinion. Different serum bicarbonate targets are used in the United Kingdom: 20–26 mEq/L for hemodialysis, 25–29 mEq/L for peritoneal dialysis, and “within normal range” for CKD (predialysis) patients. However well-intended current guidelines may be, they remain somewhat arbitrary, as specific end-points and outcome measures are lacking. Importantly, no guidelines exist for the posttransplant population. The present article by Yakupoglu et al. (3) addresses this important topic in patients with a renal graft. This retrospective study analyzes 823 kidney transplant patients with a mean venous serum bicarbonate concentration of 22.5 mEq/Landanaverageglomerularfiltrationrateof53ml/min (byCockcroft-Gaultestimation).Theauthorschosetodefine metabolic acidosis as serum bicarbonate 24 mEq/L; thus, 58%ofpatientswereacidotic.Virtuallyallsubjectshadserum calcium and phosphorus measured, however, intact parathyroid hormone (PTH) in only 51% of patients. When serum bicarbonate was divided into quartiles, it correlated positively with GFR and calcium and negatively with phosphorus, potassium, chloride, and intact PTH (iPTH). Some caution in interpretation is in order. Correlativedatadonotproveacausalrelationshipwithacidosis.The currentsetofobservationscannotruleoutthatallparameters are simply covariates of GFR. In other words, with progressive decline in renal function, we see the well-known (and unsurprising) alterations of electrolytes and iPTH. Despite the highly significantPvalues in their correlation with serum bicarbonate,themagnitudeoftheobservedchangeswasmar