Impact of early ureteric stent removal and cost-benefit analysis in kidney transplant recipients: results of a randomized controlled study.

INTRODUCTION: Duration of retaining ureteric stent in kidney transplantation is still controversial. Our study aimed to compare healthcare expenditures in kidney transplant recipients with early or routine ureteric stent removal. METHODS: This study was a post hoc analysis of data from a single-center parallel randomized controlled open-label study. Ninety patients who underwent kidney transplantation at a university-based hospital in Thailand from April 2010 to January 2011 were enrolled. Patients were randomized to early ureteric stent removal (8 days) or routine ureteric stent removal (15 days) after kidney transplantation. The costs of direct health care associated with kidney transplantation, urologic complication, and urinary tract infection (UTI) within the postoperative period among the 2 groups were compared. RESULTS: Seventy-four patients (58% living donor) fulfilled the randomized criteria (early removal, n = 37; routine removal, n = 37). By intention-to-treat analysis, incidence of UTI in early stent removal was less than the routine stent removal group (15/37, 40.5% vs 27/37, 72.9%; P = .004). Urologic complication showed no significant difference between the early and routine groups (4/37 vs 2/37; P = .39). The cost-benefit analysis of early over routine stent removal was 2390 United States dollars (USD) per patient (11,182 vs 8792 USD). Presence of UTI significantly increase the hospitalization cost of 5131 USD per patient (mean cost = 12,209 vs 7078 USD; P < .001). CONCLUSION: UTI in the early post-kidney transplantation period increases healthcare cost. Early ureteric stent removal can reduce UTI and reduce hospitalization cost. This approach shows cost-benefit in the early management of kidney transplant recipients.

Oral phosphate supplementation corrects hypophosphatemia and normalizes plasma FGF23 and 25-hydroxyvitamin D3 levels in women with chronic metabolic acidosis.

BACKGROUND: Chronic metabolic acidosis (CMA) is known to induce renal phosphate wasting and hypophosphatemia by enhancing bone resorption and inhibiting renal phosphate reabsorption. However, nothing is known regarding changes in the plasma levels of phosphate-regulating hormones during CMA, especially in humans with normal kidney function. METHODS: Fifteen healthy Thai female volunteers were given NH (4)Cl orally for 7 days to induce CMA with or without oral phosphate supplementation. Blood and 24-h urine specimens were collected prior to and after CMA induction. Plasma concentrations and fractional excretion of calcium and inorganic phosphate as well as plasma levels of fibroblast growth factor (FGF) 23, 25(OH)D (3), 1,25(OH) (2)D (3) and intact parathyroid hormone (iPTH) were determined. RESULTS: CMA led to hypophosphatemia and hypocalcemia with increases in the fractional excretion of calcium and phosphate. Plasma concentrations of FGF23, 25(OH)D (3) and iPTH were decreased, whereas that of 1,25(OH) (2)D (3) was increased. After oral phosphate supplementation, CMA-induced changes in the concentrations of the studied ions, FGF23 and 25(OH)D (3), but not those of 1,25(OH) (2)D (3) and iPTH, were diminished. CONCLUSIONS: The CMA-induced hypophosphatemia was likely to initiate a negative feedback response, thereby leading to reduction in the plasma levels of hyperphosphaturic hormones, FGF23 and PTH. An increase in the plasma 1,25(OH) (2)D (3) level, despite diminishing 25(OH)D (3) storage pool, may help enhance the intestinal phosphate absorption. Oral phosphate supplementation abolished the effects of CMA on FGF23 and 25(OH)D (3) levels, suggesting that the plasma phosphate concentration is the primary regulator of the plasma levels of these hormones during CMA.

Chronic metabolic acidosis alters osteoblast differentiation from human mesenchymal stem cells.

Bone histology of distal renal tubular acidosis patients showed decreased bone formation with impaired bone matrix mineralization that is not entirely explained by an alteration in the mineral balance. Data from in vitro studies suggests a direct inhibitory effect of metabolic acidosis on osteoblast function. We investigated the effects of chronic metabolic acidosis on osteoblast differentiation from mesenchymal stem cells (MSCs). Human MSCs were allowed to differentiate into osteoblasts in culture. Concentrated hydrochloric acid was added to the medium to lower the bicarbonate concentration and pH. The expression of various osteoblastic genes and proteins and bone matrix mineralization were examined. Chronic metabolic acidosis enhanced the messenger RNA (mRNA) and protein expression of early osteoblast transcription factor, runx-2, whereas inhibiting osterix and having no effect on ATF-4. The expression of type I collagen, the most abundant bone matrix protein, was increased following the same pattern of runx-2. Likewise, metabolic acidosis slightly enhanced the expression of mature osteoblastic gene, osteocalcin. Study on mineralization revealed suppressed alkaline phosphatase mRNA and enzyme activity. Despite the augmented collagen deposit in acidic culture, bone matrix mineralization was impaired. In conclusion, chronic metabolic acidosis alters osteoblast differentiation from MSCs through its diverse effect on osteoblastic genes and proteins resulting in an impairment of bone formation.

Soluble IL-6 receptor levels in patients on chronic hemodialysis.

Osteitis fibrosa, a part of the spectrum of renal osteodystrophy, is characterized by high bone turnover as a result of high circulating levels of parathyroid hormone (PTH). It is well accepted that the bone resorptive effects of PTH occur, at least in part, by inducing osteoblasts to secrete cytokines that stimulate both differentiation and activation of osteoclasts. One such cytokine, interleukin 6 (IL-6), exerts its actions via the IL-6 receptor (IL-6R), which has alpha and beta subunits. The alpha subunit binds IL-6 and exists in both membrane bound and soluble forms which can interact with the signal transducing components of the receptor or beta subunits and result in the same biological effect. Abnormalities in the IL-6 system have the potential to affect bone turnover and to modulate the effects of PTH. In this regard, we examined the levels of circulating soluble IL-6 receptor (sIL-6R) and plasma intact PTH in 27 patients on hemodialysis, of whom 15 were on therapy with vitamin D compounds and 12 were vitamin D naive. The results were compared to values obtained from 9 healthy controls. Blood samples were obtained pre-dialysis and sIL-6R levels were determined using a commercially available enzyme immunoassay, which measures biologically active sIL-6R. In patients on chronic hemodialysis, plasma levels of sIL-6R were 123.4 +/- 11.01 ng/ml. In healthy controls, the levels were 99.61 +/- 11.52 ng/ml, values not significantly different from those found in dialysis patients. PTH values ranged from 7-1,709 pg/ml in patients on hemodialysis; however, there was no correlation between intact PTH levels and the levels of sIL-6R. Similarly, vitamin D therapy did not influence the levels of sIL-6R. These data indicate that using an assay which is specific for biologically active sIL-6R, the levels of this receptor in patients on hemodialysis are similar to those found in normal individuals and neither the levels of PTH nor vitamin D therapy alter this aspect of IL-6 action.