Cost-Effectiveness Analysis for the Treatment of Hyperphosphatemia in Predialysis Patients: Calcium-Based versus Noncalcium-Based Phosphate Binders.

BACKGROUND: Hyperphosphatemia in chronic kidney disease (CKD) patients is often treated with calcium carbonate (CaCO3) despite the fact that CaCO3 is associated with increased calcium load and potentially increased cardiovascular risk. Alternative treatments with noncalcium-based phosphate binders do not increase the calcium load but are more costly. This study analyzes the cost-effectiveness of sevelamer versus CaCO3 for the treatment of hyperphosphatemia in stage III-V predialysis CKD patients in Malaysia. METHODS: A Markov decision model was adapted to simulate a hypothetical cohort of CKD patients requiring treatment for hyperphosphatemia. Survival was estimated by using efficacy data from the INDEPENDENT-CKD clinical trial. Cost data was obtained from Malaysian studies while health state utilities were derived from literature. Analysis was performed over lifetime duration from the perspective of the Ministry of Health Malaysia with 2013 as reference year. RESULTS: In the base case analysis, sevelamer treatment gained 6.37 life years (5.27 QALY) compared to 4.25 life years (3.54 QALY) with CaCO3. At 3% discount, lifetime costs were RM159,901 ($48,750) and RM77,139 ($23,518) on sevelamer and CaCO3, respectively. Incremental cost-effectiveness (ICER) of sevelamer versus CaCO3 was RM47,679 ($14,536) per QALY, which is less than the WHO threshold of three times GDP per capita (RM99,395) per QALY. Sensitivity analyses, both using scenario sensitivity analysis and probabilistic sensitivity analysis, showed the result to be robust. CONCLUSIONS: Our study finds that sevelamer is potentially cost-effective compared to CaCO3, for the treatment of hyperphosphatemia in predialysis CKD III-V. We propose that sevelamer should be an option in the treatment of Malaysian predialysis patients with hyperphosphatemia, particularly those with high calcium load.

Rapid detection and identification of pathogens in patients with continuous ambulatory peritoneal dialysis (CAPD) associated peritonitis by 16s rRNA gene sequencing.

Peritonitis still remains a serious complication with high rate of morbidity and mortality in patients on CAPD. Rapid and accurate identification of pathogens causing peritonitis in a CAPD patient is essential for early and optimal treatment. The aim of this study was to use 16S rRNA and ITS gene sequencing to identify common bacterial and fungal pathogens directly from the peritoneal fluid without culturing. Ninety one peritoneal fluids obtained from 91 different patients on CAPD suspected for peritonitis were investigated for etiological agents by 16S rRNA and ITS gene sequencing. Data obtained by molecular method was compared with the results obtained by culture method. Among the 45 patients confirmed for peritonitis based on international society of peritoneal dialysis (ISPD) guidelines, the etiological agents were identified in 37(82.2%) samples by culture method, while molecular method identified the etiological agents in 40(88.9%) samples. Despite the high potential application of the 16S rRNA and ITS gene sequencing in comparison to culture method to detect the vast majority of etiological agents directly from peritoneal fluids; it could not be used as a standalone test as it lacks sensitivity to identify some bacterial species due to high genetic similarity in some cases and inadequate database in Gene Bank. However, it could be used as a supplementary test to the culture method especially in the diagnosis of culture negative peritonitis.

In-centre intermittent peritoneal dialysis: a viable interim option to an eventual definitive renal replacement therapy?

In-centre intermittent peritoneal dialysis (IPD), a decade-old modality commonly associated with acute (stab) PD, continues to play an undeniably important role of providing "temporary" renal replacement therapy (RRT) in Malaysia. In our center, IPD is commenced after insertion of Tenckhoff catheter by interventional nephrologists as an interim option until a definitive RRT is established. This study aims to describe our experience and evaluate the viability of this modality as a bridging therapy. We retrospectively analyzed 39 IPD patients from January 2007 to December 2009; looking at demographics, cause of end-stage renal disease, duration on the program, length of hospitalization, PD-related infection profile, biochemical parameters and clinical outcomes. We accumulated a total experience of 169 patient-months, the average age of patients was 54.6 +/- 11.6 years, 84.6% of them diabetics. The median duration of a patient in the program was 88 days with accumulated in-hospital stay of 45 days. Eventually 48.7% of the patients secured placement for long-term haemodialysis while 20.5% were converted to CAPD. The mortality rate was 7.7% while the peritonitis rate was at 1 per 18.8 patient months. Our study shows that IPD is a viable interim option with a low infection rate and good clinical outcome.

Alkaline phosphatase predicts calcium requirements after total parathyroidectomy in patients receiving dialysis.

BACKGROUND: : It can be difficult to achieve a stable serum calcium level after parathyroidectomy for renal hyperparathyroidism. This study examined the impact of a calcium replacement protocol guided by predicted need in reducing hospital stay. METHODS: : This two-phase observational study included patients receiving dialysis who underwent parathyroidectomy. In the initial phase, a standard protocol was followed whereby oral calcium was gradually titrated upwards based on serum calcium levels. The protocol was revised in the second phase such that patients were 'loaded' with the predicted elemental calcium requirement immediately after surgery. RESULTS: : Forty-four patients were treated according to the standard protocol and 34 using the new protocol. There was a strong correlation between postoperative elemental calcium requirement and admission serum alkaline phosphatase level (ALP) (r(s) = 0.711, P < 0.001). Postoperative hospital stay was reduced from a median (range) of 5 (3-12) to 3 (2-7) days after introduction of the revised protocol as a result of better calcium balance (P < 0.001). Multivariable analysis confirmed that use of the revised protocol was the main predictor of length of stay. CONCLUSION: : ALP can predict postoperative calcium requirements and streamline hospital stay by guiding replacement therapy.

Apoptosis and the expression of genes of the Bcl-2 family and TGF-beta1 in rat renal allografts transplanted after donor-specific blood transfusion.

UNLABELLED: Factors involved in "operational" tolerance in animal models induced by recipient pre-treatment with donor-specific blood transfusion (DSBT) need elucidation. This study examined apoptosis, expression of genes of the Bcl-2 family and of TGF-beta(1) in isografts, rejecting and tolerant allografts. METHODS: Adult inbred Dark Agouti (DA) kidneys were transplanted, with immediate nephrectomy of recipient kidneys, to (1) ALLO, inbred Albino Surgery (AS) rats; (2) DSBT ALLO, AS rats who received two DA blood transfusions under cover of cyclosporine prior to transplantation; or (3) ISO, DA rats. Grafts were retrieved on day 1, 3, or 5. Apoptosis was assessed by TUNEL. RNA was extracted and reverse transcribed to cDNA for quantification by real-time PCR, relative to the 18s housekeeping gene. RESULTS: Apoptosis was negligible in ISO while it increased in allograft groups from day 1. On day 5, apoptosis in ALLO (114.0 +/- 30.6), involved renal tubular cells and leukocytes compared to DSBT ALLO (9.7 +/- 4.0) and ISO (0.9 +/- 0.3) involving leukocytes only. On day 1, DSBT ALLO had higher expression of Bax than ALLO or ISO. On day 3, DSBT ALLO and ALLO had higher TGF-beta(1) mRNA than ISO. On day 5, Bcl-2 expression was significantly decreased (P < .001) in ALLO compared to DSBT ALLO and ISO. Bad and Bid were higher in DSBT ALLO than in ALLO. TGF-beta(1) was higher in DSBT ALLO compared to ISO. CONCLUSIONS: Decreased expression of anti-apoptotic Bcl-2 gene may be implicated in increased apoptosis in rejecting allograft while expression of pro-apoptotic genes may be involved in the establishment of operational tolerance.

Distribution of blood pressure in a national sample of Malaysian adults.

We describe the distribution of blood pressure (BP) by age, sex and ethnicity in Malaysian adults. A national sample of 21,391 individuals aged 30 or older had usable data. They were selected by stratified 2-stage cluster sampling. BP was measured using an automated oscillometric device, Visomat. Percentile tables and curves by age, sex and ethnicity are presented. The systolic and diastolic BP distribution was right skewed and showed the expected increase with age. This was markedly so in Malay and other indigenous women; as a result they had most severe hypertension.

The role of protamine dose assay in reversal of heparin following extracorporeal circulation for open heart surgery.

The amount of protamine required for the neutralisation of heparin following cardiopulmonary bypass was determined by a Protamine Titration Assay using the principle of the dose--response curve and the patient's estimated blood volume. In 300 open heart surgery patients, infusion of the determined dose of protamine normalised the Activated Clotting Time (ACT) to baseline levels in 97% of these patients and produced adequate hemostasis. Our present study showed that the dose of protamine dropped to 75% of the dose calculated by conventional method of heparin to protamine ratio of 1:1. This had minimised the adverse effects of excessive protamine administration and optimised coagulation control after extracorporeal circulation.