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Abstract: Background: Calcineurin inhibitor (CNI) toxicity is a common cause of chronic allograft nephropathy. Although de novo sirolimus (SRL) with CNI minimization may provide better graft function, studies in Asian recipients are lacking. Aim: We sought to determine the 1-year outcomes of renal transplant patients who received a de novo SRL-based regimen with CNI minimization. Patients and methods: A single-center, prospective study of de novo SRL-based, reduced-dose cyclosporine regimen was performed from 2004 to 2007. The control group was a historical cohort of a cyclosporine-based regimen (cyclosporine, prednisolone, and mycophenolate mofetil). The 1-year outcome parameters included renal function, rate of acute rejection, biopsy-proven CNI toxicity, graft and patient survivals. Results: The SRL-based regimen achieved 100% 1-year graft and patient survivals. The renal function was comparable between the SRL-based and CNI-based regimens (serum creatinine 1.32 ± 0.45 and 1.45 ± 0.43 mg/dL; P = .27). The rate of biopsy-proven acute rejection was comparable (9.5% and 13%; P = .68). The SRL-based regimen had a higher rate of biopsy-proven CNI toxicity (28.5% and 9.7%; P = .03). Conclusions: De novo SRL-based regimen with CNI minimization provides excellent transplant outcomes. The strategy to minimize or withdraw CNIs may achieve excellent graft function. A prospective study targeting lower CNI trough levels in Asian transplant recipients is required. [Copyright &y& Elsevier]

Background Cytomegalovirus (CMV) infection significantly causes morbidity in kidney transplant (KT) recipients. This study aims to investigate the incidence, timing, and risk factors of CMV infection in KT recipients. Methods This is a single-center retrospective study at a tertiary referral hospital. Patients who underwent KT from January 2012 to September 2014 were included. CMV infection was defined as the presence of CMV measured by polymerase chain reaction. Logistic regression analysis was performed to assess independent risk factors of CMV infection after KT. Results Of 121 KT patients enrolled, 120 patients had CMV D + /R + serostatus, and 1 had D-/R + . CMV infection occurred in 33 (27.2%) of patients with a median follow-up time of 16 (IQR 4–25) months. Of those, 25 had CMV viremia and 8 had CMV disease mainly involving the gastrointestinal system. In total, 86% of CMV cases occurred within 3 months. All recipients received anti–IL-2 receptor antibody (IL-2 RA), low-dose rabbit antithymocyte globulin (rATG; total of 1.5 mg/kg), or standard-dose rATG (1.5 mg/kg/day for 3–5 days) for induction. Of those, the incidences of CMV infection were 19.6%, 50%, and 67%, respectively. Preemptive strategy was used in all but 1 patient in the IL-2 RA and low-dose rATG group, whereas universal prophylaxis was given in 67% of patients in the standard-dose rATG group. Independent risk factors of CMV infection were older recipient age (per 10-year increase, OR 1.5; 95% CI 1.04–2.23), and induction with standard (OR 8.19; 95% CI 2.29–34) and low-dose rATG (OR 3.87; 95% CI 1.06–12.23). Conclusions More than 25% of KT recipients developed CMV infection within 6 months after KT. The risk is increased in older recipients and induction with rATG. The level of CMV risk in low-dose rATG is 52% lower than in standard-dose rATG. In a limited-resource setting such as Thailand, deferred or preemptive strategy may be acceptable in patients who received IL-2 RA and low-dose rATG, while prophylactic therapy should be given to patients who received standard-dose rATG. [ABSTRACT FROM AUTHOR]

Background: Hemodialysis (HD) patients have higher risks of cardiovascular morbidity and mortality compared to the general population. Cardio-femoral pulse wave velocity (cfPWV) is associated with cardiovascular morbidity and mortality in HD patients. This study aimed to evaluate the prevalence and associated factors of arterial stiffness in Thai HD patients., Materials and Methods: This cross-sectional multicenter study was conducted at 4 HD centers in Bangkok, Thailand. cfPWV and peripheral blood pressure were assessed using SphygmoCor XCEL Model EM4C (AtCor medical Inc., Sydney, Australia). Significant arterial stiffness was defined by cfPWV > 10 m/s. Univariate and multivariable regression models were used to identify factors associated with arterial stiffness., Results: 144 HD patients were assessed for arterial stiffness by cfPWV measurement. The mean age of the patients was 57.8 ± 12.8 years, with 50% male and a mean dialysis vintage of 7.6 years. The mean cfPWV was 11.7 ± 3.0 m/s. The prevalence of increased arterial stiffness was 73.6%. Multivariable analysis showed that older age, hypertension, lower HD adequacy, and higher fasting plasma glucose were independently associated with arterial stiffness., Conclusion: There was a high prevalence of arterial stiffness among HD patients. Some modifiable factors found to be independently associated, including dialysis adequacy and glycemic control, should be further investigated to identify approaches to retard vascular stiffness.

Background: Calf circumference is recommended as a marker for low muscle mass and as a case finding in the diagnosis of sarcopenia. However, the cut-off value differed by ethic and region. Currently there is no study among Thai population. Therefore, we aimed to identify the optimal cutoff value of calf circumference as a screening tool for low skeletal muscle mass in independent Thai older adults. Subgroup analysis was performed for obesity and adults over 75 years., Methods: This cross-sectional cohort studied in an outpatient geriatric check-up clinic. Participants, aged 60 and above, needed to be independent in basic activities of daily living to meet the inclusion criteria. Exclusion criteria comprised active malignancy, cardiac, pulmonary, or neurovascular diseases necessitating hospitalization in the preceding three months, chronic renal diseases requiring renal replacement therapy, and unstable psychiatric disorders. We measured the maximum calf circumference and appendicular skeletal muscle mass (ASMI) using bioelectrical impedance analysis (BIA). Low muscle mass is defined according to the Asian Working Group of Sarcopenia (AWGS) 2019 consensus., Results: We enrolled 6,404 elderly adults (mean age 67.3 ± 5.1 years), with a 47% prevalence of low muscle mass in women and 25% in men. Lower muscle mass significantly correlated with reduced BMI and waist circumference in both genders (p < 0.001). Optimal cut-off values for low muscle mass screening were < 33 cm (sensitivity 80.1%, specificity 60.5%) for women and < 34 cm (sensitivity 85.4%, specificity 70.2%) for men. Subgroup analysis for those with BMI ≥ 25 kg/m² suggested raising the cut-off for women to < 34 cm (sensitivity 80.6%, specificity 54.0%) and for men to < 35 cm (sensitivity 88.7%, specificity 55.2%) to enhance specificity without substantial sensitivity loss. In the older-old adult subgroup (≥ 75 years), optimal cut-off values were < 33 cm (sensitivity 84.6%, specificity 79.9%) for women and < 34 cm (sensitivity 75.6%, specificity 87.0%) for men., Conclusions: There is a strong correlation between calf circumference and ASMI in independent Thai older adults. Calf circumference can serve as a screening tool for identifying low muscle mass. The recommended cut-off values for men and women are 34 cm and 33 cm, respectively in alignment with AWGS 2019 recommendation. Incorporating a 1-cm higher cut-off value for obese older adults improves the accuracy of muscle mass screening., Trial Registration: Thai clinical trial registry: TCTR20200511003., (© 2023. The Author(s).)

Background: Leptospirosis is one of the most important public-health zoonotic diseases in the tropics that can cause severe organ dysfunction and death. Currently there are insufficient data on long-term renal dysfunction in patients after leptospirosis infection., Methods: A prospective multicentre cohort study was conducted at 15 hospitals in the Sisaket province of Thailand. Confirmed leptospirosis patients admitted from 1 December 2015 to 30 November 2018 were followed between 1 February 2020 and 31 October 2020 (median 4.1 years after hospital discharge). The primary outcome was a composite of major kidney adverse events (MAKEs) including all-cause mortality, dialysis and new-onset chronic kidney disease (CKD)., Results: Of the 217 confirmed leptospirosis cases enrolled, 32.7% were classified as having severe leptospirosis. Fifteen cases (6.9%) were deceased at the time of hospital admission. After a median follow-up time of 4.18 years, 30 patients had died and 33 patients developed CKD. Patients with severe leptospirosis had a significantly higher risk of MAKEs {adjusted hazard ratio 2.45 [95% confidence interval (CI) 1.44-4.18]}. Patients with intensive care unit admission, pulmonary haemorrhage and acute kidney injury also had a higher risk of MAKEs and all-cause mortality. Participants with severe leptospirosis in the follow-up cohort showed a higher risk of developing CKD compared with non-severe leptospirosis [adjusted odds ratio 3.22 (95% CI 1.04-9.96)], especially renal magnesium and phosphate wasting., Conclusion: Leptospirosis patients, especially severe leptospirosis, are associated with long-term kidney sequelae. Our finding reflects the importance of long-term follow-up and the urgent need for specific interventions., (© The Author(s) 2023. Published by Oxford University Press on behalf of the ERA.)

Objective: A vegetarian very low-protein diet (VLPD) supplemented with ketoanalogues of essential amino acids Ketoanalogue-supplemented very low-protein diet (sVLPD) delays dialysis initiation in patients with chronic kidney disease (CKD). In this cost-effectiveness analysis, we compare an sVLPD with a conventional low-protein diet (LPD) in patients with CKD stage 4-5 using data from Taiwan and Thailand., Design and Methods: A Markov model simulated health outcomes and care costs in patients receiving an sVLPD (0.3-0.4 g/kg-day, vegetarian diet) supplemented with ketoanalogues (1 tablet/5 kg-day) or an LPD (0.6 g/kg-day, mixed proteins). Health state transition probability and resource cost inputs were based on published literature and local sources, respectively., Results: An sVLPD increased survival and quality-adjusted life years (QALYs) at a lower cost than an LPD. Total cost of care in Taiwan was 2,262,592.30 New Taiwan dollars (NTD) (68,059.35 EUR) with an LPD and 1,096,938.20 NTD (32,996.18 EUR) with an sVLPD (difference -1,165,654.10 NTD; -35,063.17 EUR). Total cost of care in Thailand was 500,731.09 Thai baht (THB) (14,584.12 EUR) with an LPD and 421,019.22 THB (12,262.46 EUR) with an sVLPD (difference -79,711.86 THB; -2,321.66 EUR)., Conclusion: A ketoanalogue-supplemented vegetarian sVLPD increased QALYs and lowered lifetime care costs versus an LPD in patients with predialysis CKD in Taiwan and Thailand. These data, together with the new KDOQI Guidelines for nutrition in CKD, support dietary intervention using ketoanalogue-supplemented vegetarian sVLPDs to prevent CKD progression and postpone dialysis as a cost-effective approach, with beneficial effects for patients and health care providers., (Copyright © 2022. Published by Elsevier Inc.)

The spectra of underlying genetic variants for various clinical entities including focal segmental glomerulosclerosis (FSGS) vary among different populations. Here we described the clinical and genetic characteristics of biopsy-proven FSGS patients in Thailand. Patients with FSGS pathology, without secondary causes, were included in our study. Clinical laboratory and pathological data were collected. Whole-exome sequencing (WES) was subsequently performed. 53 unrelated FSGS patients were recruited. 35 patients were adults (66.0%), and 51 patients were sporadic cases (96.2%). Clinical diagnosis before kidney biopsy was steroid-resistant nephrotic syndrome (SRNS) in 58.5%, and proteinuric chronic kidney disease in 32.1%. Using WES, disease-associated pathogenic/likely pathogenic (P/LP) variants could be identified in six patients including the two familial cases, making the P/LP detection rate of 11.3% (6/53). Of these six patients, two patients harbored novel variants with one in the COL4A4 gene and one in the MAFB gene. Four other patients carried previously reported variants in the CLCN5, LMX1B, and COL4A4 genes. Four of these patients (4/6) received immunosuppressive medications as a treatment for primary FSGS before genetic diagnosis. All four did not respond to the medications, emphasizing the importance of genetic testing to avoid unnecessary treatment. Notably, the mutation detection rates in adult and pediatric patients were almost identical, at 11.4% and 11.1%, respectively. In conclusion, the overall P/LP variant detection rate by WES in biopsy-proven FSGS patients was 11.3%. The most identified variants were in COL4A4. In addition, three novel variants associated with FSGS were detected., (© 2022. The Author(s).)

Introduction: More reports of thrombotic microangiopathy (TMA) in immunoglobulin A (IgA) nephropathy suggest its association with poor clinical outcomes. However, the prevalence and clinical significance of TMA in IgA nephropathy have not been widely studied in different populations., Methods: Kidney biopsies of all patients with primary IgA nephropathy from 1995 to 2015 at the King Chulalongkorn Memorial Hospital, Thailand, were retrospectively reviewed and reclassified by two pathologists following the Oxford MEST-C classification. TMA lesions were detected based solely on light microscopic findings. Associations between the presence of TMA and clinical data, other pathologic findings, and clinical outcomes were studied., Results: Among 267 patients with primary IgA nephropathy, 166 had adequate clinical data and kidney tissues for the analysis. TMA was observed in 21 patients (13%) and was associated with higher mean arterial pressure (MAP), history of malignant hypertension, higher proteinuria, and lower estimated glomerular filtration rate (eGFR) at diagnosis compared to those without TMA. According to the Oxford MEST-C classification, TMA showed a significant association with severe tubular atrophy/interstitial fibrosis (T2) but not with mesangial hypercellularity (M1), endocapillary hypercellularity (E1), segmental glomerulosclerosis (S1), or crescents (C1-2). After a median follow-up of 50 months, patients with TMA had a significantly higher risk of progression to end-stage kidney disease (ESKD) (hazard ratio [HR] 5.8, 95% confidence interval [CI]: 3.1-10.9) and all-cause mortality (HR 3.4, 95% CI: 1.3-8.8). After adjusting for baseline eGFR, MAP, proteinuria, and other pathological lesions, TMA remained an independent predictor of ESKD (adjusted HR 2.4, 95% CI: 1.1-5.4)., Conclusions: Kidney TMA in IgA nephropathy is associated with advanced disease stages, carries a poor prognosis, and thus should be considered in the pathological classification of IgA nephropathy., (© 2023 S. Karger AG, Basel.)

Background: Individuals with end-stage renal disease have a higher risk of hepatitis C virus (HCV) acquisition during long-term hemodialysis (HD). Our report was designed to investigate HCV prevalence and genotype, in addition to the clinical use of HCV core antigen (HCVcAg), within multiple HD facilities in Thailand., Methods: This cross-sectional report was investigated between January and June 2019. HCV infection was assessed by anti-HCV and confirmed active infection by measuring HCV RNA and HCVcAg. HCV genotype was determined by phylogenetic analysis using nucleotide sequences of NS5B region., Results: Overall, 140 of 3,305 (4.2%) patients in 15 dialysis centers had anti-HCV positive. Among them, HCV RNA was further assessed in 93 patients and was detectable in 59 (63.4%) persons. Considering HCV viremia, HCVcAg measurement exhibited high accuracy (96.8%), sensitivity (94.9%) and specificity (100%) in comparison with HCV RNA testing. Moreover, individuals infected with HCV received a longer duration of dialysis vintage when compared to anti-HCV negative controls. The major sub-genotypes were 1a, 1b, 3a, 3b, 6f and 6n. Regarding phylogenetic analysis, there were 7 clusters of isolates with high sequence homology affecting 17 individuals, indicating possible HCV transmission within the same HD centers., Conclusions: HCV frequency and common sub-genotypes in HD centers were different from those found in the Thai general population. HCVcAg might be an alternate testing for viremia within resource-limited countries. Enhanced preventive practices, dialyzer reuse policy and better access to antiviral therapy are crucial for HCV micro-elimination within HD facilities., (© 2022. The Author(s).)

Incremental hemodialysis (HD) has become an exciting approach according to the recognition of the importance of preserving residual kidney function (RKF). However, not all incident HD patients are suitable for this approach, particularly once-weekly HD. This is the first study which reported the effectiveness of once-weekly online-hemodiafiltration (OL-HDF) plus low protein diet (LPD) in incident HD patients. All stage 5 CKD patients who had chosen HD as their treatment modality at the HD center of King Chulalongkorn Memorial Hospital, Bangkok, Thailand, with RKF ⩾ 3 mL/min calculated by renal clearance of urea and urine output ⩾ 800 mL/day, started the treatment with once-weekly OL-HDF. Dietitians advised patients to consume LPD (0.6-0.8 g/kg/day) on non-dialysis days and a regular protein diet on the dialysis day (1.2 g/kg/day). Eleven incident HD patients were enrolled in the study. The mean RKF and urine volume at baseline were 4.56 ± 2.21 mL/min and 2,019.54 ± 743.73 mL/day, respectively. After 6 and 12 months of follow-up, the mean RKF of the patients who remained in the once-weekly OL-HDF protocol were 3.82 ± 1.68 mL/min and 3.28 ± 0.95 mL/min, respectively. The median duration of once-weekly OL-HDF before transitioning to twice- or thrice-weekly OL-HDF was 7 months (3-24 months). The most common indication for stepping prescription was too low RKF. We reported that dialysis initiation in the university-based center with once-weekly OL-HDF in carefully selected incident HD patients combined with LPD under serial monitoring is practical. Further studies on the clinical benefits of once-weekly OL-HDF are still required.

Leptospirosis can cause a high mortality rate, especially in severe cases. This multicenter cross-sectional study aimed to examine both host and pathogen factors that might contribute to the disease severity. A total of 217 leptospirosis patients were recruited and divided into two groups of non-severe and severe. Severe leptospirosis was defined by a modified sequential organ failure assessment (mSOFA) score of more than two or needed for mechanical ventilation support or had pulmonary hemorrhage or death. We found that leptospiremia, plasma neutrophil gelatinase-associated lipocalin (pNGAL), and interleukin 6 (IL-6) at the first day of enrollment (day 1) and microscopic agglutination test (MAT) titer at 7 days after enrollment (days 7) were significantly higher in the severe group than in the non-severe group. After adjustment for age, gender, and the days of fever, there were statistically significant associations of baseline leptospiremia level (OR 1.70, 95% CI 1.23-2.34, p = 0.001), pNGAL (OR 9.46, 95% CI 4.20-21.33, p < 0.001), and IL-6 (OR 2.82, 95% CI 1.96-4.07, p < 0.001) with the severity. In conclusion, a high leptospiremia, pNGAL, and IL-6 level at baseline were associated with severe leptospirosis., (© 2021. The Author(s).)

Objective: Hypokalemia is highly prevalent in chronic peritoneal dialysis (PD) patients worldwide, particularly in Thailand. This study aims to investigate the major determinants of hypokalemia in Thai PD patients., Methods: A cross-sectional study was performed in chronic PD patients at 4 PD centers in Bangkok, Thailand. Hypokalemia was defined if the average serum potassium level during the last 3 consecutive visits was < 3.5 mEq/L. Patients and/or their caregivers were asked to perform a 3-day dietary food record and take pre- and post-meal pictures following the instructed protocol. Daily dietary nutrients, including potassium, were estimated by a single dietician using INMUCAL-N software. Total potassium excretion was determined by 24-h PD effluents and urine collection. Intracellular and extracellular water values (ICW and ECW, respectively) were measured by electrical bioimpedance assay (BIA) to indirectly explore the role of intracellular potassium shift in hypokalemia., Results: Among 60 eligible PD patients, 19 (31%) had hypokalemia. Hypokalemic patients had significantly lower dietary potassium intake (24.4 ± 11.1 vs. 30.5 ± 9.4 mEq/day, p = 0.031) and lower total potassium excretion (28.5 ± 8.4 vs. 36.7 ± 11.2 mEq/day, p = 0.006) compared to normokalemic patients. Both groups had comparable values of ICW and ECW. On logistic regression, there was no significant correlation between hypokalemia and daily PD exchange volume, total Kt/Vurea, residual renal function, concurrent medications (insulin, diuretics, renin-angiotensin-aldosterone inhibitor, and beta-blockers) or ICW. Low dietary potassium was an independent risk factor for hypokalemia., Conclusion: Low dietary potassium intake, rather than increased potassium excretion or intracellular shift, is the major contributing factor of hypokalemia in Thai chronic PD patients. Dietary intervention or potassium supplement protocol should be implemented.

Background: Several kidney transplantation (KT) prediction models for patient and graft outcomes have been developed based on Caucasian populations. However, KT in Asian countries differs due to patient characteristics and practices. To date, there has been no equation developed for predicting outcomes among Asian KT recipients., Methods: We developed equations for predicting 5- and 10-year patient survival (PS) and death-censored graft survival (DCGS) based on 6662 patients in the Thai Transplant Registry. The cohort was divided into training and validation data sets. We identified factors significantly associated with outcomes by Cox regression. In the validation data set, we also compared our models with another model based on KT in the United States., Results: Variables included for developing the DCGS and PS models were recipient and donor age, background kidney disease, dialysis vintage, donor hepatitis C virus status, cardiovascular diseases, panel reactive antibody, donor types, donor creatinine, ischemic time, and immunosuppression regimens. The C statistics of our model in the validation data set were 0.69 (0.66-0.71) and 0.64 (0.59-0.68) for DCGS and PS. Our model performed better when compared with a model based on US patients. Compared with tacrolimus, KT recipients aged ≤44 years receiving cyclosporine A had a higher risk of graft loss (adjusted hazard ratio = 1.26; P = 0.046). The risk of death was higher in recipients aged >44 years and taking cyclosporine A (adjusted hazard ratio = 1.44; P = 0.011)., Conclusions: Our prediction model is the first based on an Asian population, can be used immediately after transplantation. The model can be accessed at www.nephrochula.com/ktmodels.

Purpose: To create a simplified ICU scoring system to predict mortality in critically ill patients that can be feasibly applied in resource limited setting with good performance of predicting hospital mortality., Materials and Methods: A retrospective study from prospective cohort was created consisting of adult patients who were admitted to an ICU of 17 centers across Thailand from 2013 to 2015. A development cohort (n = 3503) and a validation cohort (n = 1909) were randomly selected from the available enrollment data., Results: In the development cohort, the predictors of the simplified score 6 variable model were low Glasgow coma score (GCS), low mean arterial pressure or need vasopressor, positive net-fluid balance, tachypnea, thrombocytopenia, and high blood urea nitrogen. In the validation study of THAI-ICU, AUC (95%CI) was 0.81(0.78-0.83). At the optimum cutoff value of 9; the sensitivity, specificity, positive likelihood ratio were 72%, 73%, and 2.72 respectively. The Hosmer-Lemeshow - C statistic was 13.5 (p = .2) and the Brier score 95% CI was 0.16 (0.15, 0.17)., Conclusions: The THAI-ICU score is a new simplified severity score for predicting hospital mortality. The simplicity of the score will increase the possibility to apply in resource limited settings., (Copyright © 2019. Published by Elsevier Inc.)

Background: Although the levels of intact parathyroid hormone (iPTH) are well-controlled following the Kidney Disease Outcomes Quality Initiative guideline, the incidence of osteoporosis and fracture are still high in haemodialysis (HD) patients. This study was conducted to investigate the correlation between bone turnover markers, bone mineral density (BMD), and bone histomorphometry in HD patients., Methods: Twenty-two chronic HD patients were enrolled. Serum levels of bone turnover markers were measured. Double tetracycline-labelled iliac crest bone specimens were evaluated using specialized a computer program (Osteomeasure). The types of bone histomorphometry were classified based on turnover, mineralization and volume. BMD and coronary artery calcification were also determined., Results: Bone histomorphometry revealed osteitis fibrosa (50%), adynamic bone disease (45%) and mixed uremic osteodystrophy (5%). Serum iPTH level predicted high bone turnover with area under the receiver operating characteristic (ROC) of 0.833 (95% CI = 0.665-1.000, P = 0.008). Serum TRAP-5b also had ROC of 0.733 (95% CI = 0.517-0.950, P = 0.065). In addition, when using serum iPTH (cut-off 484.50 ng/mL) or serum TRAP-5b (cut-off 1.91 pg./mL) to predict high turnover, the sensitivity was 0.917. On the other hand, when both iPTH and TRAP-5B were above these cut-off, the specificity was 1.000. Low BMD and severe vascular calcification were commonly identified. However, there were no significant correlations between bone biomarkers and BMD or severe vascular calcification., Conclusion: Although iPTH levels were close to the target of Kidney Disease Outcomes Quality Initiative guideline, abnormal bone histomorphometry, BMD, and severe vascular calcification are still common. Bone biopsy is still crucially required as an accurate diagnostic tool in providing optimal guide for the treatment. © 2019 Asian Pacific Society of Nephrology., (© 2019 Asian Pacific Society of Nephrology.)

Background The effects of mycophenolic acid exposure in the early period after transplantation on clinical outcomes have been reported; however, mycophenolic acid exposure in the early period after transplantation in Asian kidney transplant recipients who receive 1.5 g/d mycophenolate mofetil has never been investigated. Objective To determine mycophenolic acid exposure on day 3 post-transplantation in kidney transplant recipiens who receive 1.5 g/d mycophenolate mofetil. The effects of the reduced renal function on mycophenolic acid area under the concentration-time curve (AUC) and the achievement of the target AUC on the incidence of biopsy proven acute rejection during the first month post-transplantation were also evaluated. Setting A university hospital Method Blood samples and 24-h urine were collected on day 3 post-transplantation. Main outcome measures The mycophenolic acid AUC was calculated by linear trapezoidal rule and compared with the target of 45 mg*h/L. Results Of 42 Thai kidney transplant recipiens, the mean mycophenolic acid AUC of 45.1 mg*h/L (SD 14.7) was comparable to the AUC target (P = 0.962). Significant differences of the mycophenolic acid AUC were observed between patients with urine output of < 2400 mL and those with urine output ≥ 2400 mL (35.3 ± 6.6 and 47.4 ± 15.2, respectively; P = 0.002), and between patients with 24-h measured CrCl < 25 mL/min and those with CrCl ≥ 25 mL/min (38.0 (29.0, 42.2) and 49.2 ± 14.0, respectively; P = 0.017). Proportions of overall biopsy proven acute rejection among patients with mycophenolic acid AUC of < 45 and ≥ 45 mg*h/L were comparable (20.0% and 23.5%, respectively; P = 1.000). Conclusions After the starting dosage of 1.5 g/d mycophenolate mofetil, the mean mycophenolic acid AUC on day 3 post-kidney transplantation is comparable with the target of 45 mg*h/L. Severely reduced renal function significantly influences mycophenolic acid exposure.

Background: Recent randomized trials have not found that polymyxin B hemoperfusion (PMX-HP) improves outcomes for patients with sepsis. However, it remains unclear whether the therapy could provide benefit for highly selected patients. Monocyte human leukocyte antigen (mHLA-DR) expression, a critical step in the immune response, is decreased during sepsis and leads to worsening sepsis outcomes. One recent study found that PMX-HP increased mHLA-DR expression while another found that the treatment removed HLA-DR-positive cells., Methods: We conducted a randomized controlled trial in patients with blood endotoxin activity assay (EAA) level ≥ 0.6. Patients in the PMX-HP group received a 2-h PMX-HP treatment plus standard treatment for 2 consecutive days. Patients in the non-PMX-HP group received only standard treatment. The primary outcome compared the groups on median change in mHLA-DR expression between day 3 and baseline. Secondary outcomes compared the groups on the mean or median change in CD11b expression, neutrophil chemotaxis, presepsin, cardiovascular Sequential Organ Failure Assessment (CVS SOFA) score, vasopressor dose, and EAA level between day 3 and baseline. We further compared the groups on mortality, ICU-free days, ventilator-free days, dialysis dependence status, renal recovery, serum creatinine, vasopressor-free days, and major adverse kidney events (MAKE 28), measured on day 28., Results: Fifty-nine patients were randomized to PMX-HP (n = 29) and non-PMX-HP (n = 30) groups. At baseline, mHLA-DR expression, CD11b, neutrophil chemotaxis, and clinical parameters were comparable between groups. The median change in mHLA-DR expression between day 3 and baseline was higher in PMX-HP patients than in patients receiving standard therapy alone (P = 0.027). The mean change in CD11b between day 3 and baseline was significantly lower in the PMX-HP group than in the non-PMX-HP group (P = 0.002). There were no significant changes from baseline in neutrophil chemotaxis, presepsin, CVS SOFA scores, vasopressor doses, or EAA level between groups. On day 28 after enrollment, mortality, ICU-free days, ventilator-free days, dialysis dependence status, renal recovery, serum creatinine, vasopressor-free days, and MAKE 28 were comparable between groups., Conclusion: PMX-HP improved mHLA-DR expression in severe sepsis patients. Future studies should examine the potential benefit of PMX-HP in patients with low mHLA-DR expression., Trial Registration: ClinicalTrials.gov, NCT02413541 . Registered on 3 March 2015.

Vitamin D, which is important for calcium homeostasis and bone metabolism, has several noncalcemic actions. Low vitamin D levels have been observed in HIV-infected patients from high latitudes, with consequently reduced bone mineral density (BMD), but data from the tropics are scarce. We aimed to determine the prevalence of and risk factors for hypovitaminosis D among HIV-infected patients in the tropics. This was a cross-sectional study to determine serum 25-hydroxyvitamin D [25(OH)D] levels in HIV-infected patients who attended our HIV clinic in Bangkok, Thailand from July 2010 to June 2011. Hypovitaminosis D was defined as vitamin D insufficiency and deficiency [25(OH)D 20-30 ng/ml and <20 ng/ml, respectively]. Hypovitaminosis D prevalence was calculated and risk factors were determined using multivariate logistic regression. A total of 673 HIV-infected adults were included. The median age was 41 years and 47% were females. The median body mass index (BMI) was 21.9 kg/m(2) and 93% were using antiretroviral therapy (ART), with a median (IQR) duration of 8.9 (5.0-10.4) years. Thirty-one percent were using efavirenz (EFV). The prevalence of vitamin D insufficiency and deficiency was 40.6% and 29.9%, respectively. In multivariate analysis, female gender [odds ratio: OR (95% confidence interval: 95% CI) 1.7 (1.2-2.3), p = 0.005], age >37 years [OR (95% CI) 1.6 (1.1-2.4), p = 0.01], and EFV use [OR (95% CI) 2.0 (1.3-3.2), p = 0.004] were independent predictors of hypovitaminosis D. Even in tropical areas where the sun is abundant, hypovitaminosis D is highly prevalent. Thus, treatment of low vitamin D in HIV-infected patients at high risk should not be ignored to prevent reductions in BMD and other hypovitaminosis D-related comorbidities.

The outcomes of kidney transplantation (KT) from hepatitis B surface antigen-positive [HBsAg(+)] donors to HBsAg(-) recipients remain inconclusive, possibly due to substantial differences in methodological and statistical models, number of patients, follow-up duration, hepatitis B virus (HBV) prophylactic regimens and hepatitis B surface antibody (anti-HBs) levels. The present retrospective, longitudinal study (clinicaltrial.gov NCT02044588) using propensity score matching technique was conducted to compare outcomes of KT between HBsAg(-) recipients with anti-HBs titer above 100 mIU/mL undergoing KT from HBsAg(+) donors (n = 43) and HBsAg(-) donors (n = 86). During the median follow-up duration of 58.2 months (range 16.7-158.3 months), there were no significant differences in graft and patient survivals. No HBV-infective markers, including HBsAg, hepatitis B core antibody, hepatitis B extracellular antigen and HBV DNA quantitative test were detected in HBsAg(+) donor group. Renal pathology outcomes revealed comparable incidences of kidney allograft rejection while there were no incidences of HBV-associated glomerulonephritis and viral antigen staining. Recipients undergoing KT from HBsAg(+) donors with no HBV prophylaxis (n = 20) provided comparable outcomes with those treated with lamivudine alone (n = 21) or lamivudine in combination with HBV immunoglobulin (n = 2). In conclusion, KT without HBV prophylaxis from HBsAg(+) donors without hepatitis B viremia to HBsAg(-) recipients with anti-HBs titer above 100 mIU/mL provides excellent graft and patient survivals without evidence of HBV transmission., (© Copyright 2014 The American Society of Transplantation and the American Society of Transplant Surgeons.)

Purpose: The high prevalence of pure red cell aplasia in Thailand has been associated with the sharp increase in number of recombinant human erythropoietin (rhEPO) copy products, based on a classical generic regulatory pathway, which have entered the market. This study aims to assess the quality of rhEPO copy products being used in Thailand., Methods: Twelve rhEPO copy products were purchased from pharmacies in Thailand, shipped under controlled cold chain conditions to the Netherlands and characterized using (1) high performance size-exclusion chromatography, (2) asymmetrical flow field-flow fractionation, (3) sodium dodecyl sulfate polyacrylamide gel electrophoresis in combination with (4) Western blotting and additionally tested for (5) host cell protein impurities as well as (6) endotoxin contamination., Results: Some of the tested rhEPO copy products showed high aggregate levels and contained a substantial amount of protein fragments. Also, one of rhEPO copy products had a high endotoxin level, exceeding the FDA limit., Conclusions: Our observations show that some of the tested copy products on the Thai market differ significantly from the originator rhEPO product, Epogen®. This comparison study supports a link between the quality attributes of copy rhEPO products and their immunogenicity.

Objective: This study was conducted to examine the effects of weight reduction on proteinuria, adipokines, and renal function in overweight immunoglobulin A nephropathy (IgAN) patients (body mass index > 23 kg/m2) with chronic proteinuria more than 6 months., Design: This was a single-center, prospective, randomized controlled trial. The study was performed at the outpatient clinic at King Chulalongkorn Memorial Hospital, Bangkok, Thailand, from July 2012 to February 2013., Subjects: Twenty-six overweight patients with chronic proteinuric biopsy-proven IgAN were randomized into a control group (n = 13) or a low-calorie normal protein diet group (n = 13). All patients received the maximum dosage of angiotensin-converting enzyme inhibitor or angiotensin receptor blocker and other antihypertensive agents to achieve a blood pressure less than 125/75 mmHg., Intervention: The study intervention was a low-calorie diet (target energy per day as 500-kcal subtraction from total energy requirement) for a 6-month period., Main Outcome Measure: At baseline and after 6 months of a low-calorie diet, body weight, body content, and clinical and laboratory parameters were determined and compared., Results: After initiating a low-calorie diet for 6 months, the normalized protein nitrogen appearance values were not different, indicating comparable protein intake. The low-calorie group had lower total daily calorie intake (1,307.1 ± 171.8 vs. 1,772.2 ± 315.4 kcal/d, P < .01) and significant reductions in body weight (-5.1 ± 3.3%, P < .001), fat content (-12.7 ± 14.1%, P < .05), and 24-hour urine protein (-45.2 ± 15.4%, P < .001). Blood pressure and renal function parameters were unaltered. The low-calorie group had approximately 20% lower plasma levels of leptin but unchanged adiponectin. There were positive correlations between the amount of protein reduction and the changes of body weight, fat mass, and leptin., Conclusions: A 6-month low-calorie diet leads to weight reduction and results in diminished fat content and decreased proteinuria in overweight IgAN patients with chronic proteinuria. This beneficial effect might be mediated by changes in adipokines., (Copyright © 2014 National Kidney Foundation, Inc. Published by Elsevier Inc. All rights reserved.)

Objective: Understanding how best to measure renal function in HIV-infected patients is critical because estimated glomerular filtration rate (eGFR) in HIV-infected patients can be affected by ethnicity and body composition. We validated the available eGFR equations and compared them to the plasma Tc-diethylenetriaminepentaacetic acid (Tc-DTPA) clearance in HIV-infected patients., Design: Test of diagnostic accuracy., Methods: One hundred and ninety-six HIV-infected patients underwent measuring of Tc-DTPA plasma clearance, five creatinine-based eGFR equations, cystatin-C GFR, and 24-h urine creatinine clearance (CrCl)., Results: Mean (SD) Tc-DTPA GFR was 117.7 ± 29.2 ml/min per 1.73 m. The re-expressed Modification of Diet in Renal Disease (MDRD), Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI), re-expressed MDRD formula with Thai racial correction factor, Thai eGFR equation, Cockcroft-Gault equation, cystatin-C GFR, and 24-h urine CrCl underestimated the reference GFR. The bias estimated by the mean of differences (SD) for the re-expressed MDRD equation, CKD-EPI, re-expressed MDRD formula with Thai racial correction factor, Thai eGFR, Cockcroft-Gault equation, cystatin-C, and 24-h urine CrCl can be expressed as 18.9 ± 27.3, 11.1 ± 25.5, 6.2 ± 28.8, 15.4 ± 27.0, 30.4 ± 28.0, 3.2 + 36.1, and 5.0 ± 12.1 ml/min per 1.73 m, respectively., Conclusion: The available eGFR equations underestimated GFR in HIV-infected adults. However, the eGFR by cystatin-C GFR was the most precise and accurate. Among creatinine-based eGFR equations, re-expressed MDRD formula with Thai racial correction factor was the most precise and accurate. The racial factor for each ethnicity is important and the existing eGFR equation should be validated before using it in the HIV population.

Objective: Implementation of the "Peritoneal Dialysis-First (PD First)" policy, mandating PD as the first modality of renal replacement therapy for end-stage renal disease patients under universal health coverage, leads to a rapid growth of PD cases and centers in Thailand. Since PD-related infection is the Achilles' heel of PD, this retrospective study was conducted to examine the magnitude of PD-related infection in Thailand under the "PD First" policy., Material and Method: All PD centers in Thailand were included in the present study. PD nurse specialists in each center were requested to review medical records of all patients undergoing PD during October 1, 2009 to September 30, 2010 and to submit data to the main investigators., Results: Eighty-eight percent of all active PD-centers in Thailand (102 out of 116) participated in the present study. One hundred and thirty-three nephrologists and 220 PD nurse specialists served 8,201 PD prevalent patients in these centers (7,925 CAPD and 276 APD). The overall exit-site infection (ESI) rate was 1 episode/37.7 patient-month (0.32 episodes/patient-year) while the overall peritonitis rate was 1 episode/25.5 patient-month (0.47 episode/patient-year)., Conclusion: Despite the rapid growth of PD cases under the limited resource, the PD-related infection rates in Thailand are only small degree behind the goal of Asia-Pacific Key Performance Indicators (KPIs) Task Force.

Background: Currently, estimated glomerular filtration rate (eGFR) equations have been validated only in Caucasians and African-Americans and is not applicable to people of other races/ethnicities as shown in studies conducted in two Asian populations: Chinese and Japanese. Because of this, it is important that eGFR equations are validated in its prospective population before applying it in the clinical setting and in epidemiologic studies. Therefore, we examined all eGFR equations available: reexpressed isotope dilution mass spectroscopy (IDMS)-traceable Modification of Diet in Renal Disease (MDRD) equation, Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation, Chinese equation and Japanese equation., Methods: A total of 350 adult Thai CKD patients were studied. The (99m)Tc-DTPA plasma clearance was used as a reference for glomerular filtration rate (GFR). The serum creatinine was determined by IDMS reference enzymatic methods (Cr(Enz)) and Jaffe's kinetic assay (Cr(Jaffe)) as indicated in each equation., Results: The disagreement between the reference GFR and eGFR (reference GFR minus eGFR) was 9.6 mL/min/1.73 m(2) for the reexpressed IDMS-traceable MDRD equation, 8.0 mL/min/1.73 m(2) for CKD-EPI equation, 1.9 mL/min/1.73 m(2) for eGFR equation from the Chinese study and 20.9 mL/min/1.73 m(2) for the eGFR equation from the Japanese study. The Thai coefficient for the reexpressed MDRD was 1.129. The reexpressed MDRD equation for Thais is as follows: 175 × Cr(Enz) ((-1.154)) × Age ((-0.203)) × 0.742 (if female) × 1.129 (if Thai). When stepwise multiple regression analysis was used, the Thai eGFR formula is: 375.5 × Cr(Enz) ((-0.848)) × Age ((-0.364)) × 0.712 (if female)., Conclusions: Differences in race/ethnicity can significantly affect the results obtained from MDRD-based eGFR equation. It is highly recommended that each population should validate eGFR equations before applying the equation in epidemiologic studies or clinical use.

Objective: The national health insurance fund in Thailand initiated by the national health security act in November, 2002. In October 2007, the national health insurance fund launched the first renal replacement therapy (RRT) reimbursement plan by the "Peritoneal Dialysis-First" (PD First) policy. The rationale of the PD First Policy resulted from the perspective that PD for end stage renal disease (ESRD) treatment offers the most economic and efficient outcome. The present study was conducted to determine whether the increase of RRT penetration by national health policy could impact the national RRT prevalence., Material and Method: The Thailand Renal Replacement Therapy (TRT) database in 2007, 2008, and 2009 were retrieved and analyzed., Results: By TRT registry data, the total yearly prevalence of RRT increased by an average of 14.8% after the implementation of national health insurance and the "PD First" policy from 2007 to 2009. The total yearly prevalence of hemodialaysis (HD) modestly increased (14.7%) while the total yearly prevalence of PD remarkably expanded by 107.3%. The yearly incidence of all RRT modalities increased by an average of 34.8% in 2007 to 2009. The yearly incidence of HD modestly increased (8.1%) while the total yearly incidence of PD remarkably elevated by 157.8%. Civil Servants Medical Benefit Compensation (CSMBS) was the major funding source of RRT cases (34.5%) while national health insurance funding was the second major funding source (26.0%). From 2007-2009, the CSMBS funding was the majority of HD while national health insurance funding was the majority of PD. The sharing of PD by national health insurance increased from 33.9% in 2007, 58.6% in 2208, and 77.2% in 2009., Conclusion: The coverage ofESRD patients by national health insurance fund by the "PD First" policy impacted the RRT prevalence and incidence both the total prevalence and total incidence due to the universal penetration to RRT treatment of Thai population. Also, the policy altered the RRT modality predisposition. PD modality willfinally be the majority ofThaiRRT modalities if the policy can be managed successfully.

Recombinant human erythropoietin (r-HuEpo) has been used for the treatment of renal anemia. With the loss of its patent protection, there has been an upsurge of more affordable biosimilar agents, increasing patient access to treatment for these conditions. The complexity of the manufacturing process for these recombinant proteins, however, can result in altered properties that may significantly affect patient safety. As it is not known whether various r-HuEpo products can be safely interchanged, we studied 30 patients with chronic kidney disease treated by subcutaneous injection with biosimilar r-HuEpo and who developed a sudden loss of efficacy. Sera from 23 of these patients were positive for r-HuEpo-neutralizing antibodies, and their bone marrow biopsies indicated pure red-cell aplasia, indicating the loss of erythroblasts. Sera and bone marrow biopsies from the remaining seven patients were negative for anti-r-HuEpo antibodies and red-cell aplasia, respectively. The cause for r-HuEpo hyporesponsiveness was occult gastrointestinal bleeding. Thus, subcutaneous injection of biosimilar r-HuEpo can cause adverse immunological effects. A large, long-term, pharmacovigilance study is necessary to monitor and ensure patient safety for these agents.

Background: In Thailand, dialysate endotoxin contamination levels vary from less than 0.001 to 2.0 EU/ml. This difference has prompted an investigation on the production of proinflammatory cytokines and counter-inflammatory mediators of peripheral blood mononuclear cells (PBMCs) after high-flux dialysis., Methods: Patients from four hemodialysis (HD) centers who met the inclusion/exclusion criteria were enrolled into the study. PBMCs were isolated by Ficoll density gradient centrifugation and cultured. Supernatants were tested for interleukin 6 (IL-6), IL-1β and IL-1 receptor antagonist (IL-1Ra) concentration by ELISA., Results: HD centers 1, 2, 3 and 4 had mean dialysate endotoxin contamination levels of 0.001, 0.026, 0.558 and 1.960 EU/ml, respectively. HD center 4 had the highest levels of IL-6 (1,052.3 ± 240.7 pg/10(6) PBMCs), IL-1β (1,297.1 ± 334.6 pg/10(6) PBMCs) and IL-1Ra (2,713.4 ± 1,255.3 pg/10(6) PBMCs). There were no significant differences in cytokine production between HD centers 1 and 2., Conclusion: Our study showed that ultrapure dialysate can minimize the risk of stimulating inflammatory cells. Ultrapure dialysate may prevent or delay endotoxin exposure-related complications., (Copyright © 2011 S. Karger AG, Basel.)

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.

Post-infectious glomerulonephritis is one of the most common causes of acute glomerulonephritis. A retrospective study of post-infectious glomerulonephritis at King Chulalongkorn Memorial Hospital, Thailand was performed from January 1999 to December 2005. Among thirty six patients, eight cases were post-streptococcal glomerulonephritis and twenty eight cases were post non-streptococcal Glomerulo Nephritis (GN). Most cases present with edema, hypertension, gross hematuria and nephrotic-range proteinuria. C3 and CH50 commonly were low. Post-streptococcal glomerulonephritis had more aggressive pathology compared to the others. However the long term outcome was excellent. In the present study the authors found ESRD in only 14.3% (4 out of 28 cases) that reflects the excellent prognosis of post-infectious glomerulonephritis. Of interest, all of the ESRD patients were caused by post non-Streptococcal GN. Even though, no statistic was achieved; it might reflect the aggressiveness of non-Streptococcal pathogen.

The authors report the first case of chylous ascites and chyluria in a 65-year-old Thai women with nephrotic syndrome due to focal segmental glomerulosclerosis (FSGS), tip variant. She presented with generalized edema and abdominal discomfort. Abdominal paracentesis revealed milky white fluid. Chylous ascites was confirmed. Abdominal and thoracic computed tomography did not show any cause of chylous ascites and chyluruia. Lymphoscintigraphy could not demonstrate lymph flow obstruction and connection between lymphatic pathway and KUB system. Those could have explained the chylous ascites or chyluria. Hypoalbuminemia-induced bowel edema may predispose to change the permeability of mucosal or serosal lymphatics. This could result in chylous ascites but the cause of chyluria could not be determined in this case.

Objectives: To determine the prevalence and risk factors of osteoporosis after renal transplantation in Thai patients., Material and Method: A single-center cross-sectional study of bone mineral density was conducted in 102 Thai renal allograft recipients. Correlations were made between the clinical parameters and the occurrences of osteoporosis., Results: The prevalence of osteoporosis was 24.5%, 9.8% and 26.4% at lumbar vertebrae, hip region, and any sites, respectively. Binary logistic regression analysis revealed that cumulative dosage of steroids was significantly correlated with osteoporosis of the lumbar spine (p = 0.023, adjusted OR = 1.005), while body mass index (p = 0.005, adjusted OR = 0.738) and age (p = 0.052, adjusted OR = 1.077) were correlated with osteoporosis of the hip region., Conclusion: Osteoporosis is common in Thai renal allograft recipients, particularly of the lumbar vertebrae. Cumulative dosage of steroids is the most important risk factor of low BMD of the lumbar vertebrae.

Sirolimus, a novel immunosuppressive drug, has been used in kidney transplant recipients to minimize calcineurine inhibitor (CNI) and steroid toxicities. Likewise CNI, Sirolimus's pharmacokinetics have both inter and intra-individual pharmacokinetic variations. Due to ethnic differences, the recommended oral loading dose of 6 mg and oral maintenance dose of 2 mg per day for Caucasian patients and oral loading dose of 10 mg and oral maintenance dose of 5 mg per day for African-American patients may not be appropriate for Asian recipients. We, therefore conducted the pharmacokinetic study of sirolimus in Thai population, aimed to delineate the appropriate sirolimus dose for further clinical use. The study was performed in 12 healthy Thai volunteers. After an over night fasting, a single oral dose of 6 mg sirolimus was given. The complete pharmacokinetic study was done by UVhigh performance liquid chromatography (HPLC-UV) to measure the whole blood sirolimus level at 0.5 hour after the dose (C0.5) and then C1, C1.5, C2, C2.5, C3, C4, C6, C8, C12, and C24 hours. A complete area under the concentration time curve from 0-24 hours (AUC(0-24 hr)) was calculated by using the trapezoidal rule. The mean (+/- SD) time to maximal concentration (Tmax) was 1.45 +/- 0.5 hr (range 1-3 hrs). The maximal (Cm) and minimal plasma concentration (Ctroug) for sirolimus were 25.3 +/- 6.1 ng/ml (range 18.10 - 40 ng/ml) and 4.47 +/- 0.57 ng/ml (range 2.90 - 7.20) ng/ml respectively. The AUC(0-24 hr) were 187.9 +/- 48.2 ng * hr/ml (range 151.3 - 294.8 ng * hr/ml). Sirolimus level at 4 hr post-dose had the best of correlation with AUC(0-24 hr) (Pearson correlation = 0.76, p < 0.007). One volunteer had a very high sirolimus level. This subject's pharmacokinetic data showed AUC(0-24 hr) of 256 ng * hr/ml and Cmax of 40 ng/ml. In conclusion, the oral loading dose of 6 mg of sirolimus in Thai volunteers did not achieve the recommended therapeutic level (5-10 ng/ml) in most subjects. There are differences in pharmacokinetics of sirolimus between Thais and Caucasians.

Background: The nationwide renal registry has not yet been organized in Thailand, and the literature contains no registry of renal pathologic finding across the Southeast Asian (SEA) countries in the modern era when electron microscopy (EM) is routinely available., Objective: The aim of the present study was to examine the prevalence of renal pathology in Thai population., Material and Method: The authors reviewed the case file and renal biopsy specimens of King Chulalongkorn University Hospital to identify all adult native renal biopsy specimens received from January 2001 to December 2004, investigating prevalence and clinical and histological data. Biopsy of renal graft and in cases of trauma and tumors the authors excluded. Most of the biopsy specimens obtained The authorsre analyzed using light microscopy (LM), immunofluorescense (IF), and EM. Final diagnosis was made for each patient based on clinicopathologic correlations., Results: A total of 506 native renal biopsies were processed during this period, 69.8% were female and 30.2% were male. Their age average was 37 +/- 14.2 (13-80) years. The most common indications for renal biopsy were nephrotic syndrome and SLE (36.8%, 34.5%, respectively), followed by asymptomatic hematuria/proteinuria in 10.9% of patients. Secondary glomerular diseases were dominant against primary diseases in all but elderly age group (>50 years), particularly LN. Among primary glomerular diseases, the prevalence of IgAN, focal segmental glomerulosclerosis, and membranous nephropathy were 31.0%, 24.9%, and 13.1%, respectively. The provisional clinical diagnosis was correct in three fourths (73.2%) of the SLE cases. Postbiopsy complications occurred in 3.3% (17/506). Gross hematuria was seen in 2.3% (12/506), and perinephric hemptoma in 0.79%. Three of them required blood transfusion but none of them died and required an invasive procedure for resolution. The major complications were 2 folds less than regular prevalence (0.6% compared to 1.3%)., Conclusion: Although the data was collected from single center where EM is routinely performed, the authors believe that IgAN is the commonest primary GN in SEA countries. The authors are looking forward to seeing the nationwide registry data in Thailand and other SEA countries.

Profiling of absorption of cyclosporine (CsA) microemulsion is a concept in therapeutic drug monitoring (TDM) designed to optimize the clinical benefits of the drug in transplant recipients. A single blood concentration at 2 h (C(2)) after CsA microemulsion administration in kidney transplant recipients accurately predicts graft outcome. An international guidelines has recommended the target C(2) over time-course post-transplantation. We determined whether this recommendation is appropriate for our patients who are Asian ethnic. The clinical data of these C(2) monitoring kidney transplant recipients were compared with the historical cohort of microemulsion CsA trough (C(0)) level monitoring during the first 24-month post-transplantation. The inclusion and exclusion criteria were applied for both C(2) and C(0) cohorts. The mean target C(2) concentrations at 1, 3, 6, and 12-month post-transplantation were achieved in the C(2) cohort as the international guildlines. At 3-month post-transplantation, patients who had C(2) concentrations over 1500 ng/mL had higher serum creatinine as compared with those who had C(2) levels <1300 ng/mL (2.23 +/- 0.8 vs. 1.44 +/- 0.38 mg/dL: p = 0.01). Also, at 6-month post-transplantation, patients who had C(2) concentrations over 1300 ng/mL had higher serum creatinine (1.96 +/- 0.29 vs. 1.37 +/- 0.34 mg/dL: p < 0.01) as compared with those who had C(2) levels <1100 ng/mL. There was no statistical difference of acute rejection episodes between the two cohorts. The international consensus for C(2) concentraion may be too high for Asian ethnic kidney transplant recipients. The data from this study indicated lower than recommended C(2) concentraion as an appropriate C(2) target concentraion.

The existence of a human immunodeficiency virus (HIV)-associated nephropathy (HIVAN) as a distinct disease entity characterized by glomerulosclerosis is well established in North America and Western Europe. Although the large number of HIV-infected cases overwhelm the Asian countries, no cases of HIVAN are documented in the literature. We studied 26 cases of HIV-infected Thai patients with proteinuria greater than 1.5 g/d of protein during 1995 and 1996. None of the patients were treated with antiretroviral drugs at the time of renal biopsy. Intravenous drug addiction and sexual transmission were risk factors in 11 and 15 patients, respectively. Pathological examinations were performed by light microscopic and immunoperoxidase study. Mesangial proliferative glomerulonephritis was found in 17 cases, immunoglobulin A (IgA) nephropathy in 2 cases, and diffuse proliferative glomerulonephritis and interstitial nephritis secondary to cryptococcal infection in 2 cases each. One case each had membranous glomerulopathy, membranoproliferative glomerulonephritis, and granulomatous interstitial nephritis secondary to tuberculosis. The renal pathological findings of HIVAN with the unique features described in previous literature were not evident in these patients. Although the data in this study are limited to 26 HIV-infected Thai patients, we believe that HIVAN is uncommon in the Asian HIV-infected population.