Correction of metabolic acidosis with potassium citrate in renal transplant patients and its effect on bone quality

Abstract

Background: Acidosis and transplantation are associated with increased risk of bone disturbances. This study aimed to assess bone morphology and metabolism in acidotic patients with a renal graft, and to ameliorate bone characteristics by restoration of acid/base homeostasis with potassium citrate.

Methods: This was a 12-month controlled, randomized, interventional trial that included 30 renal transplant patients with metabolic acidosis (S-[HCO(3)(-)] <24 mmol/L) undergoing treatment with either potassium citrate to maintain S-[HCO(3)(-)] >24 mmol/L, or potassium chloride (control group). Iliac crest bone biopsies and dual-energy X-ray absorptiometry were performed at baseline and after 12 months of treatment. Bone biopsies were analyzed by in vitro micro-computed tomography and histomorphometry, including tetracycline double labeling. Serum biomarkers of bone turnover were measured at baseline and study end. Twenty-three healthy participants with normal kidney function comprised the reference group.

Results: Administration of potassium citrate resulted in persisting normalization of S-[HCO(3)(-)] versus potassium chloride. At 12 months, bone surface, connectivity density, cortical thickness, and cortical porosity were better preserved with potassium citrate than with potassium chloride, respectively. Serological biomarkers and bone tetracycline labeling indicate higher bone turnover with potassium citrate versus potassium chloride. In contrast, no relevant changes in bone mineral density were detected by dual-energy X-ray absorptiometry.

Conclusions: Treatment with potassium citrate in renal transplant patients is efficient and well tolerated for correction of metabolic acidosis and may be associated with improvement in bone quality. This study is limited by the heterogeneity of the investigated population with regard to age, sex, and transplant vintage.

Trial registration: ClinicalTrials.gov NCT00913796.

Figures

Figure 1.

Correction of metabolic acidosis from potassium citrate versus potassium chloride administration and associated effects on serum potassium concentration. (A) Changes in serum bicarbonate concentration (S-HCO3−) over 12 months in relation to potassium citrate or potassium chloride intake. (B) Changes in serum potassium concentration over 12 months in relation to potassium citrate or potassium chloride intake. *P≤0.05 versus potassium chloride; †P≤0.05 versus baseline for potassium chloride; ‡P≤0.01 versus baseline for potassium citrate. S, serum; M, month.

Figure 2.

Bone mineral density (BMD) measurements by dual x-ray absorptiometry at the lumbar spine, total hip, and femoral neck in g/cm2. (A) Results are given in absolute terms for healthy reference participants (Reference) and renal transplant patients before (Baseline) and after 12 months of treatment (Follow-up) with potassium citrate (K-Cit) or potassium chloride (K-Cl). (B) Results are given for renal transplant patients as percentage of change between baseline and 12 months of treatment with potassium citrate (K-Cit) or potassium chloride (K-Cl).

Figure 3.

Bone spongiosa microarchitecture (µCT) of iliac crest samples from patients taking potassium citrate or potassium chloride at baseline and after 12 months of treatment (follow-up), as well as of living organ donors (reference value). Results are given as absolute values (A, C, E, G, I, and K) or percentage changes (B, D, F, H, J, and L) for the respective variables. B, D, F, H, J, and L are boxplots, representing the median, 25th and 75th percentiles, and 2 SDs of the mean percentage changes for potassium citrate and potassium chloride, respectively, between follow-up and baseline. Ref., reference; BL, baseline; FU, follow-up; K-Cit, potassium citrate; K-Cl, potassium chloride; BV, bone volume; TV, total volume; BS, bone surface; Tb.Th, trabecular thickness; Tb.N, trabecular number; Conn.D, connectivity density; BMD, bone mineral density.

Figure 4.

Bone corticalis microarchitecture (µCT) of iliac crest samples from patients taking potassium citrate or potassium chloride at baseline and after 12 months of treatment, as well as of living organ donors (reference value). Ref., reference; K-Cit, potassium citrate; K-Cl, potassium chloride; Ct.Th, cortical thickness; BV, bone volume; TV, total volume; CT.Po, cortical porosity.

Figure 5.

Bone characteristics assessed by histomorphometry of iliac crest samples from patients taking potassium citrate or potassium chloride at baseline and after 12 months of treatment, as well as of living organ donors (reference value). Results are given as absolute values for bone characteristics assessed by histomorphometry analysis. †Denotes the P value for significance between the reference population of healthy individuals and the combined renal transplant patients. Ref., reference; K-Cit, potassium citrate; K-Cl, potassium chloride.

Figure 6.

Serologic biomarkers of bone metabolism. Results are given as absolute values in boxplots, representing the median, 25th and 75th percentiles, and 2 SDs. †Denotes the P value for significance between the reference population of healthy individuals and the combined renal transplant patients. Ref., reference; K-Cit, potassium citrate; K-Cl, potassium chloride; PINP, N-terminal propeptide of precollagen I; CTX, C-terminal telopeptide/CrossLaps.