Early as compared to late initiation of twice-weekly hemodialysis and short-term survival among end-stage renal disease patients.

INTRODUCTION: The impact of timing of hemodialysis (HD) for end-stage renal disease (ESRD) patients treated with twice-weekly HD remains unclear. We aimed to determine the effects of late initiation of HD on short-term mortality and hospitalization. METHODS: A multicenter cohort study was conducted in 11 HD centers in Northeastern Thailand (HEmodialysis Network of the NorthEastern Thailand study group). We recruited adult ESRD patients who were treated with twice-weekly HD for more than 3 months and had data on eGFR at HD initiation. Clinical and laboratory values at the time of recruitment were recorded. Late and early (eGFR at start <5 and >5 ml/min/1.73 m2 ) initiations were defined. Outcomes were disease-related death (excluding any accidental deaths) and first hospitalization. Data analysis was performed by multivariable cox-regression analysis. FINDINGS: A total of 407 patients who had data on eGFR at HD initiation (303 in late group and 104 in early group) were included for analysis. There were 56.8% male with a mean age of 55 years. During the 15.1 months of follow-up, there were 27 (6.6%) disease-related deaths. The 1-year survival rate was similar among late and early initiation groups. The incidence density of first hospitalization in the late group was significantly lower than those in the early group (HR adjusted, 0.63; 95% CI, 0.40-0.99, p = 0.047). Among 303 patients who were in the late start group, patients with diabetes had a higher mortality rate (HR, 3.49; 95% CI, 1.40-8.70, p = 0.007) when compared to non-diabetic patients. DISCUSSION: Early initiation of HD at eGFR >5 ml/min/1.73 m2 had no short-term survival benefit compared to the late group in ESRD patients treated with twice-weekly HD for at least 3 months in a resource-limited setting. A survival benefit from an early start of HD was found among diabetic patients.

CKDNET, a quality improvement project for prevention and reduction of chronic kidney disease in the Northeast Thailand.

BACKGROUND: The incidence of chronic kidney disease (CKD) is high in the Northeast Thailand compared to other parts of the country. Therefore, a broad program applying all levels of care is inevitable. This paper describes the results of the first year trial of the Chronic Kidney Disease Prevention in the Northeast Thailand (CKDNET), a quality improvement project collaboratively established to curb CKD. METHODS: We have covered general population, high risk persons and all stages of CKD patients with expansive strategies such as early screening, effective CKD registry, prevention and CKD comprehensive care models including cost effectiveness analysis. RESULTS: The preliminary results from CKD screening in general population of two rural sub-districts show that 26.8% of the screened population has CKD and 28.9% of CKD patients are of unknown etiology. We have established the CKD registry that has enlisted a total of 10.4 million individuals till date, of which 0.13 million are confirmed to have CKD. Pamphlets, posters, brochures and other media of 94 different types in the total number of 478,450 has been distributed for CKD education and awareness at the community level. A CKD guideline that suits for local situation has been formulated to deal the problem effectively and improve care. Moreover, our multidisciplinary intervention and self-management supports were effective in improving glomerular filtration rate (49.57 versus 46.23 ml/min/1.73 m2; p < 0.05), blood pressure (129.6/76.1 versus 135.8/83.6 mmHg) and quality of life of CKD patients included in the program compared to those of the patients under conventional care. The cost effectiveness analysis revealed that lifetime cost for the comprehensive health services under the CKDNET program was 486,898 Baht compared to that of the usual care of 479,386 Baht, resulting in an incremental-cost effectiveness ratio of 18,702 Baht per quality-adjusted life years gained. CONCLUSION: CKDNET, a quality improvement project of the holistic approach is currently applying to the population in the Northeast Thailand which will facilitate curtailing of CKD burden in the region.

Mortality and treatment costs of hospitalized chronic kidney disease patients between the three major health insurance schemes in Thailand.

BACKGROUND: Thailand has reformed its healthcare to ensure fairness and universality. Previous reports comparing the fairness among the 3 main healthcare schemes, including the Universal Coverage Scheme (UCS), the Civil Servant Medical Benefit Scheme (CSMBS) and the Social Health Insurance (SHI) have been published. They focused mainly on provision of medication for cancers and human immunodeficiency virus infection. Since chronic kidney disease (CKD) patients have a high rate of hospitalization and high risk of death, they also require special care and need more than access to medicine. We, therefore, performed a 1-year, nationwide, evaluation on the clinical outcomes (i.e., mortality rates and complication rates) and treatment costs for hospitalized CKD patients across the 3 main health insurance schemes. METHODS: All adult in-patient CKD medical expense forms in fiscal 2010 were analyzed. The outcomes focused on were clinical outcomes, access to special care and equipment (especially dialysis), and expenses on CKD patients. Factors influencing mortality rates were evaluated by multiple logistic regression. RESULTS: There were 128,338 CKD patients, accounting for 236,439 admissions. The CSMBS group was older on average, had the most severe co-morbidities, and had the highest hospital charges, while the UCS group had the highest rate of complications. The mortality rates differed among the 3 insurance schemes; the crude odds ratio (OR) for mortality was highest in the CSMBS scheme. After adjustment for biological, economic, and geographic variables, the UCS group had the highest risk of in-hospital death (OR 1.13;95 % confidence interval (CI) 1.07-1.20; p < 0.001) while the SHI group had lowest mortality (OR 0.87; 95 % CI 0.76-0.99; p = 0.038). The circumscribed healthcare benefits and limited access to specialists and dialysis care in the UCS may account for less favorable comparison with the CSMBS and SHI groups. CONCLUSIONS: Significant differences are observed in mortality rates among CKD patients from among the 3 main healthcare schemes. Improvements in equity of care might minimize the differences.

A 25-year experience of kidney transplantation in Thailand: report from the Thai Transplant Registry.

AIM: To report the kidney transplant activity and survival data during the past 25 years from the Thai Transplant Registry. METHODS: By using the registry database that was collected and updated yearly by 26 transplant centres across the country, we have reported the donor, recipient, and transplant characteristics during the past 25 years from 1987 to 2012. The primary outcome was graft loss that was defined as return to dialysis, graft removal, retransplant, or patient death. RESULTS: 465 kidney transplants were performed in 2012, an 8.1% and 23.0% increase in living and deceased donor transplants compared to the previous year, respectively. Between 1987 and 2012 with the data of 3808 recipients, patient survival and graft survival improved significantly. Traffic accident was the most common cause of death in brain-dead donors. Additionally, the most common cause of end-stage kidney disease was glomerulonephritis. Infection has been among the most common causes of death in kidney transplant recipients. CONCLUSION: We have reported the total number, the graft and the patient survival data of kidney transplant recipients in Thailand for the period from 1987 to 2012. Although the number of patients is much lower than that in the developed countries, the patients and the graft survival rates are comparable.

Dialysis dose and risk factors for death among ESRD patients treated with twice-weekly hemodialysis: a prospective cohort study.

BACKGROUND/AIMS: We aimed to define the dosing and risk factors for death in patients undergoing twice-weekly hemodialysis. METHODS: A prospective multi-center cohort study was conducted with one-year observation. Patients treated with twice- or thrice-weekly hemodialysis were identified. Death and first admission were the outcomes. spKt/V was a factor of interest. RESULTS: We enrolled 504 twice-weekly and 169 thrice-weekly hemodialysis patients. The mean weekly values of spKt/V in the two groups were 3.4 and 5.1. The one-year survival rate and times to hospitalization were similar in both groups. The hazard ratios for death in higher spKt/V quartile was not associated with lower mortality, p = 0.70. The four significant predictors for death were serum albumin, HR = 2.6, current smoking, HR = 19.3, age, HR = 1.1, and the Index of Coexistent Disease [ICED], HR = 1.9. CONCLUSION: The effect of spKt/V on short-term mortality was not obvious in twice-weekly dialysis patients. Attention should be paid to patients who smoke, have hypoalbuminemia, are elderly, or have a high ICED.

Impact of the heterozygous TPMT*1/*3C genotype on azathioprine-induced myelosuppression in kidney transplant recipients in Thailand.

BACKGROUND: Thiopurine S-methyltransferase (TPMT) is a polymorphic enzyme associated with detoxification of azathioprine, an immunosuppressant used after renal transplantation in several Asian countries. Patients with variations of the TPMT gene may be at risk for myelosuppression after they receive a standard dosage of the drug. The frequency of TPMT*3C has been reported to be higher in the Thai population than in other Asian populations, possibly putting the Thais at higher risk for myelosuppression. OBJECTIVE: The aim of this study was to assess the impact of the heterozygous TPMT*1/*3C genotype on azathioprine-induced myelosuppression in kidney transplant recipients in Thailand. METHODS: This study was conducted at Srinagarind Hospital, Khon Kaen University, Khon Kaen, Thailand, and Chulalongkorn Hospital, Chulalongkorn University, Bangkok, Thailand. Eligible patients underwent kidney transplantation from deceased or living-related donors from 1984 to 2007. Electronic medical records were assessed retrospectively for the 6-month period after initiation of azathioprine treatment. TPMT genotyping and phenotyping were studied prospectively using real-time polymerase chain reaction and biochemical assay, respectively. The odds ratios (ORs), sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) were determined. RESULTS: A total of 139 patients were enrolled (89 men, 50 women; median age, 42 years [range, 17-70 years]; mean weight, 58 kg [range, 37-87 kg]). The heterozygous TPMT*1/*3C genotype was found in 9 of the 139 patients (6.47%) (95% CI, 3.00-11.94). The TPMT activity of those patients was significantly lower than that of patients with the homozygous wild-type genotype (median, 21.37 vs 37.12 nmol 6-methylthioguanine/g . Hb/h, respectively; P < 0.001). The risk for azathioprine-induced myelosuppression in the patients with the heterozygous TPMT*1/*3C genotype was significantly higher than that in patients with the wild-type genotype (adjusted OR, 14.18 [95% CI, 3.07-65.40]; P < 0.005). The sensitivity and specificity of TPMT*3C genotyping for the prediction of azathioprine-induced myelosuppression in these kidney transplant recipients were 27% and 97%, respectively. Assuming a prevalence of azathioprine-induced myelotoxicity of 7% according to previously published data, the PPV and NPV were estimated to be 50% and 95%, respectively. CONCLUSION: In these kidney transplant recipients, patients who carried the TPMT*3C allele were at a higher risk for azathioprine-induced myelosuppression than noncarriers.

The association of anti-r-HuEpo-associated pure red cell aplasia with HLA-DRB1*09-DQB1*0309.

BACKGROUND: Anti-r-HuEpo associated PRCA developed in patients received subcutaneous injection of r-HuEpo for treatment of renal anemia in chronic kidney disease. This adverse immunological effect of r-HuEpo causes sudden loss of r-HuEpo efficacy, low circulating reticulocyte count and bone marrow biopsy shows an absence of erythroid precursor cells with normal cell population of non-erythroid lineage. There are postulation cause of anti-r-HuEpo associated PRCA including genetic factor, immunogenicity factor, storage and handlings factor and formulation of r-HuEpo product. Previous observation of our report showed an aggregation of HLA-DRB1*09 in four anti-r-HuEpo associated PRCA cases. This allele is rare in Caucasian (<1%) but more common in Thai population (8.4-12.5%). This study was aimed to investigate the possible association between HLA-DRB1*09 or other specific HLA and anti-r-HuEpo associated PRCA. METHODS: Twenty two cases of proven anti-r-HuEpo associated PRCA were recruited and studied retrospectively based on the incidence report of serious adverse drug reaction. The EDTA bloods were drawn for HLA typing using sequence specific primer polymerase chain reaction (SSP-PCR). The HLA data of 1,800 potential cadaveric kidney transplantation recipients in the waiting list as chronic kidney disease control and 1,500 potential bone marrow stem cell donors in national stem cell registry as healthy population control were retrieved from the database of Thai Red Cross for comparison. RESULTS: The distribution of gene frequency of HLA-A, -B, -DR and -DQ alleles in anti-r-HuEpo associated PRCA cases showed high gene frequency of HLA-A*02, HLA-A*11 and HLA-A*24 for HLA-A loci, HLA-B*18, HLA-B*46, HLA-B*60 and HLA-B*62 for HLA-B loci, and HLA-DRB1*09, HLA-DRB1*12 and HLA-DRB1*15 for HLA-DR loci. There was a significant difference of HLA-DRB1*09 gene frequency (P < 0.001) which associated with HLA-DQB1*0309 between anti-r-HuEpo associated PRCA cases, and potential cadaveric kidney transplantation in the waiting list or potential national stem cell registry donor. The odd ratio of HLA-DRB1*09 allele for anti-r-HuEpo associated PRCA was 2.89 (95% CI: 1.88-4.46; p-value: <0.001). CONCLUSIONS: Our data demonstrated the association of HLA-DRB1*09-DQB1*0309 and anti-r-HuEpo associated PRCA cases. This association may be used in identifying the risk of the patients.

Bone histology and bone mineral density after correction of acidosis in distal renal tubular acidosis.

BACKGROUND: The association between chronic metabolic acidosis and alterations in bone cell functions has been demonstrated in vitro and in animal studies. However, the causal role of acidosis and the effects of alkaline therapy on bone histology and bone mineral density in chronic metabolic acidosis have never been systematically demonstrated in humans. This study was conducted to examine the alterations in bone mineral density and bone histology before and after correction of acidosis among patients with distal renal tubular acidosis (dRTA) METHODS: Correction of metabolic acidosis by potassium citrate was done in non-azotemic dRTA patients, 6 females and 4 males, who had never received long-term alkaline therapy before enrolling into this study. Blood chemistries, serum intact parathyroid hormone, and 24-hour urine collection for the determination of urinary calcium, phosphate, sodium, potassium, bone mineral density determination, and transiliac bone biopsy were done in all patients at baseline and after one year of potassium citrate therapy. RESULTS: Significant elevations in serum bicarbonate (16.5 +/- 3.0 vs. 24.6 +/- 2.8 mEq/L, P < 0.05) and urinary potassium excretion (35.2 +/- 7.9 vs. 55.4 +/-3.5 mEq/L, P < 0.05) were observed after potassium citrate therapy. No significant alterations in other serum and urine electrolytes were found after the therapy. Serum intact parathyroid hormone level was also significantly elevated after one year of treatment (12.8 +/- 7.3 vs. 26.2 +/- 8.7 pg/mL, P < 0.05). Bone formation rate was significantly suppressed at baseline and was normalized by the treatment (0.02 +/- 0.02 vs. 0.06 +/- 0.03 microm(3)/microm(2)/day, P < 0.05). There were non-significant elevations in trabecular bone volume, osteoblastic and osteoclastic numbers. Bone mineral densities in dRTA patients were also significantly decreased below normal values in most studied areas at baseline and were significantly elevated at the trochanter of femur (0.677 +/- 0.136 vs. 0.748 +/- 0.144 g/c m(2), P < 0.05) and total femur (0.898 +/- 0.166 vs. 0.976 +/- 0.154 g/c m(2), P < 0.05) after the treatment. CONCLUSIONS: This study demonstrates that alkaline therapy corrects abnormal bone cell function and elevates bone mineral density in dRTA patients, indicating the causal role of acidosis in the alterations of bone cell functions and reduction in bone mineral density. Parathyroid gland activity also may be involved in the adaptation of the body to chronic metabolic acidosis.