Quantitative assessment of glomerular basement membrane collagen IV α chains in paraffin sections from patients with focal segmental glomerulosclerosis and Alport gene variants.

Focal segmental glomerulosclerosis (FSGS) lesions have been linked to variants in COL4A3/A4/A5 genes, which are also mutated in Alport syndrome. Although it could be useful for diagnosis, quantitative evaluation of glomerular basement membrane (GBM) type IV collagen (colIV) networks is not widely used to assess these patients. To do so, we developed immunofluorescence imaging for collagen α5(IV) and α1/2(IV) on kidney paraffin sections with Airyscan confocal microscopy that clearly distinguishes GBM collagen α3α4α5(IV) and α1α1α2(IV) as two distinct layers, allowing quantitative assessment of both colIV networks. The ratios of collagen α5(IV):α1/2(IV) mean fluorescence intensities (α5:α1/2 intensity ratios) and thicknesses (α5:α1/2 thickness ratios) were calculated to represent the levels of collagen α3α4α5(IV) relative to α1α1α2(IV). The α5:α1/2 intensity and thickness ratios were comparable across all 11 control samples, while both ratios were significantly and markedly decreased in all patients with pathogenic or likely pathogenic Alport COL4A variants, supporting validity of this approach. Thus, with further validation of this technique, quantitative measurement of GBM colIV subtype abundance by immunofluorescence, may potentially serve to identify the subgroup of patients with FSGS lesions likely to harbor pathogenic COL4A variants who could benefit from genetic testing.

Prevalence of arterial stiffness and associated factors in Thai hemodialysis patients: A multicenter cross-sectional study.

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.

Clinicopathological Characteristics and Impacts on Clinical Outcomes of Thrombotic Microangiopathy Lesions in Patients with Immunoglobulin A Nephropathy in Thailand.

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.

Long-term kidney outcomes after leptospirosis: a prospective multicentre cohort study in Thailand.

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.

Effect of canagliflozin in non-diabetic obese patients with albuminuria: A randomized, double-blind, placebo-controlled trial.

BACKGROUND: Sodium-glucose co-transporter 2 inhibitor (SGLT2i) has been shown to improve renal outcomes in both diabetic and non-diabetic kidney disease. However, the effect of SGLT2i on renal outcomes in patients with non-diabetic obesity is still not established. MATERIALS AND METHODS: In this double-blind, randomized controlled trial, we assigned non-diabetic patients with body mass index (BMI) ≥ 25 kg/m2, persistent 24-hour urine albumin-creatinine ratio (UACR) ≥ 10 mg/gCr, and estimated glomerular filtration rate (eGFR) ≥ 60 mL/min/1.73m2, who had been treated with renin-angiotensin system blockade, to canagliflozin 100 mg daily or placebo for 24 weeks. The reduction in UACR and eGFR at 12 and 24 weeks were explored. (Thai Clinical Trials Registry 20190203003). RESULTS: Of 247 non-diabetic obese patients screened, 32 patients met inclusion criteria and underwent randomization. The median baseline of UACR was 69.1 mg/gCr. There were no statistically significant differences in albuminuria reduction between the groups at 12 weeks and 24 weeks. The estimated GFR in the canagliflozin group decreased significantly from baseline at 12 weeks (-5.39 mL/min/1.73m2; 95% CI -9.81 to -0.97; p = 0.017) but not at 24 weeks (-1.16 mL/min/1.73m2; 95% CI -5.58 to 3.26; p = 0.66), and there was no significant change from baseline in the placebo group at both 12 and 24 weeks. CONCLUSION: Canagliflozin 100 mg daily was well tolerated but did not significantly reduce UACR in non-diabetic obese patients with microalbuminuria. However, a significant temporary decline in eGFR might reflect a subtle reduction in glomerular hyperfiltration.

Calf circumference as a screening tool for low skeletal muscle mass: Cut-off values in independent Thai older adults.

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.

Economic Analysis of a Ketoanalogue-Supplemented Very Low-Protein Diet in Patients With Chronic Kidney Disease in Taiwan and Thailand.

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.

Lactobacillus rhamnosus L34 attenuates chronic kidney disease progression in a 5/6 nephrectomy mouse model through the excretion of anti-inflammatory molecules.

BACKGROUND: Although pathogenic gut microbiota causes gut leakage, increases translocation of uremic toxins into circulation and accelerates CKD progression, the local strain of Lactobacillus rhamnosus L34 might attenuate gut leakage. We explored the effects of L34 on kidney fibrosis and levels of gut-derived uremic toxins (GDUTs) in 5/6 nephrectomy (5/6Nx) mice. METHODS: At 6 weeks post-5/6Nx in mice, either L34 (1 × 106 CFU) or phosphate buffer solution (as 5/6Nx control) was fed daily for 14 weeks. In vitro, the effects of L34-conditioned media with or without indoxyl sulfate (a representative GDUT) on inflammation and cell integrity (transepithelial electrical resistance; TEER) were assessed in Caco-2 (enterocytes). In parallel, the effects on proinflammatory cytokines and collagen expression were assessed in HK2 proximal tubular cells. RESULTS: At 20 weeks post-5/6Nx, L34-treated mice showed significantly fewer renal injuries, as evaluated by (i) kidney fibrosis area (P < 0.01) with lower serum creatinine and proteinuria, (ii) GDUT including trimethylamine-N-oxide (TMAO) (P = 0.02) and indoxyl sulfate (P < 0.01) and (iii) endotoxin (P = 0.03) and serum TNF-α (P = 0.01) than 5/6Nx controls. Fecal microbiome analysis revealed an increased proportion of Bacteroidetes in 5/6Nx controls. After incubation with indoxyl sulfate, Caco-2 enterocytes had higher interleukin-8 and nuclear factor κB expression and lower TEER values, and HK2 cells demonstrated higher gene expression of TNF-α, IL-6 and collagen (types III and IV). These indoxyl sulfate-activated parameters were attenuated with L34-conditioned media, indicating the protective role of L34 in enterocyte integrity and renal fibrogenesis. CONCLUSION: L34 attenuated uremia-induced systemic inflammation by reducing GDUTs and gut leakage that provided renoprotective effects in CKD.

Prevalence and genotype distribution of hepatitis C virus within hemodialysis units in Thailand: role of HCV core antigen in the assessment of viremia.

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.

Effects of phosphate binders on bone biomarkers and bone density in haemodialysis patients.

AIM: The incidences of osteoporosis, fracture and vascular calcification increase concordantly with the progression of chronic kidney disease (CKD). CKD-mineral bone disease (CKD-MBD) induced by hyperphosphatemia is a major pathophysiologic mechanism. The effects of phosphate binders on bone turnover biomarkers and bone mineral density (BMD) in haemodialysis patients are still inconclusive. Our aim is to demonstrate the effects of these phosphate binders on different aspects of CKD-MBD. METHODS: We conducted a prospective cohort of 65 haemodialysis patients to investigate the effect of 12-month monotherapy of phosphate binders composing calcium-based phosphate binders (CPB) or non-calcium-based phosphate binders (NCPB), including sevelamer and lanthanum, on bone turnover biomarkers and BMD changes. The performance of bone turnover biomarkers to predict low BMD was attentively determined. RESULTS: When compared with CPB, NCPB use was associated with higher levels of bone turnover biomarkers. NCPB was also associated with lower BMD at lumbar and distal radius. Total procollagen type 1N-terminal propeptide (P1NP), bone-specific alkaline phosphatase (BALP), and tartrate-resistant acid phosphatase 5b (TRAP5b) provided the best performance for diagnosing low BMD in haemodialysis patients. CONCLUSION: Switching from CPB to NCPB might increase bone biomarkers and prevent the development of adynamic bone disease. On the contrary, NCPB should be cautiously used in haemodialysis patients who already had low BMD. P1NP, BALP and TRAP5b could be used to guide the appropriate management, including anti-resorptive and anabolic medications, and predict low BMD in haemodialysis patients treated with phosphate binders.

Development and validation of point-of-care testing of albuminuria for early screening of chronic kidney disease.

INTRODUCTION: Chronic kidney disease (CKD) is a significant global health issue. As the prevalence of renal replacement therapy (RRT) in Thailand is increasing, early detection and management of CKD is the most important step to prevent CKD progression and the need for RRT. Current diagnostic tests for CKD are non-specific and expensive. We aimed to develop and validate antibody-based-albumin point-of-care testing (POCT) to detect patients with impaired kidney function at early stage. METHODS: The prototype strip test was developed under the concept of competitive lateral flow immunochromatography assay, or strip test. Monoclonal antibodies (MAbs) to human serum albumin (HSA) were harvested from the hybridomas of spleen cells from immunized mice and mouse myeloma cells. Presence of MAbs was detected by enzyme-linked immunosorbent assay (ELISA). Spot urine was obtained from patients with kidney disease, type I, or type II Diabetes Mellitus upon their visit at King Chulalongkorn Memorial Hospital during 2018-2019. All samples were analyzed for urine albumin with our POCT (CU microalbumin) and the other two commercial POCTs (Microalbu PHAN and MICRAL). The results were validated against standard method for urine microalbumin measurement. A urine microalbumin concentration of less than 20 ug/ml was defined as normal. The sensitivity, specificity, and predictive values were calculated in comparison with the standard laboratory method. RESULT: A total of 100 adult patients were included. CU microalbumin had a sensitivity of 86%, a specificity of 94%, and a positive predictive value of 96%. Our POCT showed good correlation with the laboratory results. CONCLUSION: CU microalbumin correlated well with the standard method for quantitative measurement of urine albumin. Therefore, it has the potential for early screening of CKD, especially in primary health care facilities in resource limited settings.

Protein-Energy Wasting and Mortality Risk Prediction Among Peritoneal Dialysis Patients.

OBJECTIVES: Protein-energy wasting (PEW) is defined as the loss of body protein and energy reserves associated with kidney disease. However, the extent to which PEW contributes to increased mortality among peritoneal dialysis (PD) patients remains unclear. METHODS: This is a retrospective cohort study from 2012 to 2020. The PEW was diagnosed by applying at least 3 of the 4 following criteria: (1) altered serum biochemistry indicated by a serum albumin level of <3.5 g/L; (2) decreased body mass status identified by a body mass index (BMI) of <23 kg/m2 or <10% total body fat; (3) muscle wasting defined by the lean tissue index, calculated as a lean tissue mass normalized to the height-squared in the <10th percentile of the reference population; and (4) low dietary protein intake determined by the normalized protein equivalent of a total nitrogen appearance of <0.8 g/kg/day. The Malnutrition Inflammation Score (MIS) was also examined as an alternative tool for assessment of PEW. RESULTS: The average age of the 555 participants was 57.5 ± 12.6 years. The prevalence of PEW was 27.3%, with 196 deaths observed during the mean follow-up of 25.5 months. Patients with PEW who fulfilled at least 3 of the 4 listed criteria had a higher risk of death in the unadjusted model (hazard ratio 1.61, 95% confidence interval 1.19-2.18, P = .002). However, these associations were attenuated after adjusting for potential confounders. Regarding the individual PEW criterion, decreased serum albumin and low muscle mass were significantly associated with mortality in the multivariable models. In contrast, decreased body mass and low protein intake were not associated with a higher risk of death. High MIS (≥5 points) and each one-point increase in the MIS were also significantly associated with higher risk of death in both unadjusted and adjusted models. CONCLUSIONS: Among PD patients, the presence of PEW was not a better predictor of all-cause mortality than either the altered serum biochemistry (albumin) or low muscle mass criteria. The MIS performed well as an independent predictor of death and might be an option for assessment of PEW status in the PD population.

Epidemiology and short-term outcomes of acute kidney injury among patients in the intensive care unit in Laos: a nationwide multicenter, prospective, and observational study.

BACKGROUND: Acute kidney injury (AKI) has become a global health issue. Little is known about the disease burden in Laos. We aimed to evaluate the burden and outcomes of AKI as well as assess the availability of AKI treatment in Laos. METHODS: We performed a multicentric prospective observational study in adult patients who had been admitted to 5 intensive care units (ICU) in Laos. The data was serially collected on the first 28 days of ICU admission. Patients were diagnosed by the KDIGO 2012 criteria for AKI. We used AKI occurrence as the primary outcome and explored risk factors on the development and outcomes of AKI. RESULTS: We enrolled 1480 patients from 5 ICU centers across Laos from January to December 2016. After excluding patients with end-stage renal disease and those with incomplete data, AKI occurred in 508 of the 1460 enrolled patients (34.8%). Overall, the rates of maximum AKI staging were 4% for stage 1, 10.3% for stage 2, and 20.5% for stage 3. Risk factors for AKI were older age, obesity, cardiovascular diseases, respiratory diseases, renal diseases, oncologic diseases, and chronic kidney diseases. Only 1.8% of all participants received RRT. The mortality rate was 28.4% in non-AKI patients compared to 44.5% in AKI patients, which increased according to the stage of AKI (stage 1, 4.9%; stage 2, 28.3%; stage 3 66.8%; P < 0.001). There were 13.6% who were discharged against medical advice. CONCLUSIONS: AKI is a huge burden in Laos with under-recognition and poor outcomes.

Impact of Serum Bicarbonate Levels on Muscle Mass and Kidney Function in Pre-Dialysis Chronic Kidney Disease Patients.

BACKGROUND: Treatment of metabolic acidosis to target the higher serum bicarbonate level than guideline recommendation may downregulate muscle protein degradation and improve renal function among chronic kidney disease (CKD) patients. We conducted a study to test the effects of increased serum bicarbonate level on muscle parameters, nutrition, and renal function in pre-dialysis CKD patients. METHODS: This was a randomized, controlled study. CKD stage 3-4 patients with serum HCO3- <22 mEq/L were randomized to either receive oral sodium bicarbonate with high target bicarbonate level of 25 ± 1 or standard level of 22 ± 1 mEq/L as control group using protocol-based titration of dosage adjustment. The changes of muscle mass measured by bioelectrical impedance analysis (BIA), muscle strength by hand grip dynamometer, estimated glomerular filtration rate (eGFR) using CKD-Epidemiology Collaboration equation, nutritional markers, and muscle-related biomarkers were determined. Data at baseline and after 4 months of sodium bicarbonate supplementation were compared between groups using Student t test or chi-square test as appropriate. RESULTS: Forty-two patients completed the study (n = 21 per group). The mean age and eGFR were 61.2 ± 9.8 years and 32.4 ± 14.1 mL/min respectively. Serum bicarbonate levels at baseline were 21.0 ± 2.1 mEq/L. Baseline data including sex, diabetes, serum bicarbonate level, creatinine, and blood pressure were similar. After 4 months of treatment, the average serum bicarbonate levels in both groups were 24.0 ± 1.4 and 20.7 ± 2.3 mEq/L (p < 0.001). Both BIA-derived total-body muscle mass and appendicular lean balance were increased at 4 months in the higher bicarbonate group (26.0 ± 5.3 to 26.7 ± 5.5 kg, p = 0.04 and 19.8 ± 4.1 to 20.7 ± 4.4 kg, p = 0.06, respectively) despite comparable body weight and protein intake. Patients in the high bicarbonate group had a significant reduction of plasma myostatin levels, a surrogate of muscle degradation, at the study exit after adjusting for baseline values (-3,137.8; 95% CI -6,235.3 to -40.4 pg/mL, p= 0.04), but unaltered insulin-like growth factor-1 level, as the mediator of muscle cell growth, (141 [106-156] to 110 [87-144] ng/mL, p = 0.13) compared to the control group. Muscle strength, eGFR as well as serum prealbumin were not significantly different between 2 groups (p > 0.05). Neither worsening hypertension nor congestive heart failure was found throughout the study. CONCLUSION: Bicarbonate supplementation to achieve the serum level ∼24 mEq/L demonstrates better muscle mass preservation in patients with pre-dialysis CKD. The impact of alkaline therapy on renal function may require a longer period of study.

The epidemiology and characteristics of acute kidney injury in the Southeast Asia intensive care unit: a prospective multicentre study.

BACKGROUND: Etiologies for acute kidney injury (AKI) vary by geographic region and socioeconomic status. While considerable information is now available on AKI in the Americas, Europe and China, large comprehensive epidemiologic studies of AKI from Southeast Asia (SEA) are still lacking. The aim of this study was to investigate the rates and characteristics of AKI among intensive care unit (ICU) patients in Thailand. METHODS: We conducted the largest prospective observational study of AKI in SEA. The data were serially collected on the first 28 days of ICU admission by registration in electronic web-based format. AKI status was defined by full Kidney Disease: Improving Global Outcome criteria. We used AKI occurrence as the clinical outcome and explored the impact of modifiable and non-modifiable risk factors on the development and progression of AKI. RESULTS: We enrolled 5476 patients from 17 ICU centres across Thailand from February 2013 to July 2015. After excluding patients with end-stage renal disease and those with incomplete data, AKI occurred in 2471 of 4668 patients (52.9%). Overall, the maximum AKI stage was Stage 1 in 7.5%, Stage 2 in 16.5% and Stage 3 in 28.9%. In the multivariable adjusted model, we found that older age, female sex, admission to a regional hospital, medical ICU, high body mass index, primary diagnosis of cardiovascular-related disease and infectious disease, higher Acute Physiology and Chronic Health Evaluation II, non-renal Sequential Organ Failure Assessment scores, underlying anemia and use of vasopressors were all independent risk factors for AKI development. CONCLUSIONS: In Thai ICUs, AKI is very common. Identification of risk factors of AKI development will help in the development of a prognostic scoring model for this population and should help in decision making for timely intervention, ultimately leading to better clinical outcomes.

Clinical and subclinical acute kidney injury in multidrug-resistant septic patients treated with colistimethate sodium: Incidence and clinical outcomes.

AIM: Colistimethate sodium (CMS) has been postulated as the principal cause of high incidence of clinical acute kidney injury (AKI) in multidrug-resistance (MDR) septic patients with normal baseline serum creatinine (sCr) who were treated with CMS. This prospective observational study was conducted to examine the incidence and clinical outcomes of clinical and subclinical AKI in MDR septic patients receiving CMS. METHODS: Forty-two MDR septic patients with normal sCr who required CMS were included. Clinical AKI was diagnosed by increased sCr levels according to the KDIGO2012 criteria while subclinical AKI was identified by elevated levels of urinary neutrophil gelatinase-associated lipocalin (uNGAL > 150 ng/mL) or urinary liver-type fatty-acid-binding protein (uL-FABP > 10.5 ng/mL). RESULTS: Clinical AKI was noted in 47.6% of patients on day 5 and 38.1% on day 7 after initiating CMS. By using uL-FABP, subclinical AKI was observed in 45.2% and 54.8% on day 5 and 7, respectively. At baseline prior to CMS treatment, subclinical AKI was already present in 90%. The baseline uL-FABP was superior to the baseline uNGAL in early prediction of clinical AKI on day 5. The subclinical AKI patients had comparable worse outcomes as clinical AKI patients. CONCLUSION: The incidence of subclinical AKI in MDR septic patients before CMS treatment was extremely high. The baseline uL-FABP provided the best predictive capacity of clinical AKI. The causes of clinical AKI might include the persistence of sepsis process, subclinical AKI and CMS nephrotoxicity. Proper management of subclinical AKI patients before CMS initiation should be concerned to prevent further renal damage and improve patient and renal outcomes.

Bone turnover markers predict type of bone histomorphometry and bone mineral density in Asian chronic haemodialysis patients.

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.

Intraperitoneal Cefepime Monotherapy Versus Combination Therapy of Cefazolin Plus Ceftazidime for Empirical Treatment of CAPD-Associated Peritonitis: A Multicenter, Open-Label, Noninferiority, Randomized, Controlled Trial.

RATIONALE & OBJECTIVE: Compared to combination therapy, intraperitoneal (IP) cefepime monotherapy for continuous ambulatory peritoneal dialysis (CAPD)-associated peritonitis may provide potential benefits in lowering staff burden, shortening time-consuming antibiotic preparation, and reducing bag contamination risk. This study sought to evaluate whether cefepime monotherapy is noninferior to combination regimens. STUDY DESIGN: Multicenter, open-label, noninferiority, randomized, controlled trial. SETTING & PARTICIPANTS: Adult incident peritoneal dialysis (PD) patients with CAPD-associated peritonitis in 8 PD centers in Thailand. INTERVENTIONS: Random assignment to either IP monotherapy of cefepime, 1g/d, or IP combination of cefazolin and ceftazidime, 1g/d, both given as continuous dosing. OUTCOMES: Primary end point: resolution of peritonitis at day 10 (primary treatment response). SECONDARY OUTCOMES: initial response (day 5), complete cure (relapse/recurrence-free response 28 days after treatment completion), relapsing/recurrent peritonitis, and death from any cause. Noninferiority would be confirmed for the primary outcome if the lower margin of the 1-sided 95% CI was not less than-10% for difference in the primary response rate. A 2-sided 90% CI was used to demonstrate the upper or lower border of the 1-sided 95% CI. RESULTS: There were 144 eligible patients with CAPD-associated peritonitis, of whom 70 and 74 patients were in the monotherapy and combination-therapy groups, respectively. Baseline demographic and clinical characteristics were not different between the groups. The primary response was 82.6% in the monotherapy group and 81.1% in the combination-therapy group (treatment difference, 1.5%; 90% CI, -9.1% to 12.1%; P=0.04). There was no significant difference in the monotherapy group compared with the combination-therapy group in terms of initial response rate (65.7% vs 60.8%; treatment difference, 4.9%; 95% CI, -10.8% to 20.6%; P=0.5) and complete cure rate (80.0% vs 80.6%; treatment difference, -0.6%; 95% CI, -13.9% to 12.8%; P=0.7). Relapsing and recurrent peritonitis occurred in 4.6% and 4.6% of the monotherapy group and 4.2% and 5.6% of the combination-therapy group (P=0.9and P=0.8, respectively). There was nominally higher all-cause mortality in the monotherapy group (7.1% vs 2.7%; treatment difference, 4.4%; 95% CI, -2.6% to 11.5%), but this difference was not statistically significant (P = 0.2). LIMITATION: Not double blind. CONCLUSIONS: IP cefepime monotherapy was noninferior to conventional combination therapy for resolution of CAPD-associated peritonitis at day 10 and may be a reasonable alternative first-line treatment. FUNDING: This study is supported by The Kidney Foundation of Thailand (R5879), Thailand; Rachadaphiseksompotch Fund (RA56/006) and Rachadaphicseksompotch Endorsement Fund (CU-GRS_61_06_30_01), Chulalongkorn University, Thailand; National Research Council of Thailand (156/2560), Thailand; and Thailand Research Foundation (IRG5780017), Thailand. TRIAL REGISTRATION: Registered at ClinicalTrials.gov with study number NCT02872038.

Maximizing anti-HBs seroresponsiveness in kidney transplant waitlist patients: A tertiary-center perspective
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BACKGROUND: Patients on dialysis are at risk of hepatitis B virus (HBV) infection, and antibodies against the hepatitis B surface antigen (anti-HBs) ≥ 10 IU/L are required. However, a high percentages of HBV vaccine nonresponders have been reported. We aimed to determine the optimal HBV vaccination protocol. MATERIALS AND METHODS: Kidney transplant waitlisted patients were followed for 12 months and categorized into two groups. Group A included patients with sustained anti-HBs ≥ 10 IU/L who did not require vaccination. Group B consisted of patients with anti-HBs < 10 IU/L who were treated with a course of 4 double-dose HBV vaccinations. Without seroconversion after the first course, a second course was initiated. A third course, coadministered with the tetanus-diphtheria (Td) vaccine, was performed upon failure of the second course. RESULTS: A total of 266 patients were included, 140 were categorized into group A and 126 into group B. Higher serum phosphorus, hemoglobin, and antibodies against the hepatitis core antigen (anti-HBc) were associated with sustaining anti-HBs ≥ 10 IU/L without vaccination. Diabetes mellitus (DM) was associated with the need for vaccination. For group B, 107 patients required 1 course of vaccination, 15 patients required 2 courses, and 4 patients required the third course with Td vaccine coadministration. Long dialysis vintage and low hemoglobin level were associated with seroconversion failure after the first course. CONCLUSION: Serum phosphorus, hemoglobin, DM, anti-HBc, and dialysis vintage were associated with the anti-HBs seroresponsiveness and sustainability. Our 3-course of 4 double-dose HBV vaccines regimen (with Td vaccine in the final course) conferred immunity to all patients.

The effectiveness of cinacalcet: a randomized, open label study in chronic hemodialysis patients with severe secondary hyperparathyroidism.

BACKGROUND: Secondary hyperparathyroidism (SHPT) is associated with high incidences of cardiovascular disease, bone fracture, and mortality. This study was conducted to demonstrate the effectiveness of cinacalcet treatment on chronic kidney disease-mineral bone disorder (CKD-MBD) markers in chronic hemodialysis patients with severe SHPT. METHODS: In phase 1, 30 adult HD patients were randomized to cinacalcet or control groups for 12 weeks to explore the achievement of >30% reduction of iPTH. In phase 2, 45 patients were participated to further explore the effect of cinacalcet on CKD-MBD parameters for 24-week follow up and 12 additional weeks after cinacalcet discontinuation. RESULTS: In phase 1, the baseline serum iPTH levels were not different [1374 (955, 1639) pg/mL in the control group vs. 1191 (1005, 1884) pg/mL in the cinacalcet group], the percentage of patients achieving iPTH target were significantly higher in the treatment group [80% vs. 13%, p = .001]. In phase 2, the significant reductions of iPTH, FGF-23, tartrate-resistant acid phosphatase 5b, and slightly decreased size of parathyroid gland and stabilized vascular calcification were observed at 24-week follow up and markedly rebounded after discontinuation of cinacalcet. CONCLUSIONS: The effectiveness of cinacalcet were still obviously demonstrated even in chronic HD patients with severe SHPT. In addition, the improvements of bone markers and FGF-23, and stabilization of vascular calcification were observed. Therefore, cinacalcet can provide salutary effects on CKD-MBD in severe SHPT and might be an initially effective PTH-lowering therapy prior to surgical parathyroidectomy as well as an alternative treatment in the patients unsuitable for surgery. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov: NCT02056730. Date of registration: February 4, 2014.