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BackgroundHealth information systems (HIS) are fundamental tools for the surveillance of health services, estimation of disease burden and prioritization of health resources. Several gaps in the availability of HIS for kidney disease were highlighted by the first iteration of the Global Kidney Health Atlas.MethodsAs part of its second iteration, the International Society of Nephrology conducted a cross-sectional global survey between July and October 2018 to explore the coverage and scope of HIS for kidney disease, with a focus on kidney replacement therapy (KRT).ResultsOut of a total of 182 invited countries, 154 countries responded to questions on HIS (85% response rate). KRT registries were available in almost all high-income countries, but few low-income countries, while registries for non-dialysis chronic kidney disease (CKD) or acute kidney injury (AKI) were rare. Registries in high-income countries tended to be national, in contrast to registries in low-income countries, which often operated at local or regional levels. Although cause of end-stage kidney disease, modality of KRT and source of kidney transplant donors were frequently reported, few countries collected data on patient-reported outcome measures and only half of low-income countries recorded process-based measures. Almost no countries had programs to detect AKI and practices to identify CKD-targeted individuals with diabetes, hypertension and cardiovascular disease, rather than members of high-risk ethnic groups.ConclusionsThese findings confirm significant heterogeneity in the global availability of HIS for kidney disease and highlight important gaps in their coverage and scope, especially in low-income countries and across the domains of AKI, non-dialysis CKD, patient-reported outcomes, process-based measures and quality indicators for KRT service delivery.

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Aim: We conducted a prospective cohort study to evaluate the effectiveness of an integrated care model on delaying chronic kidney disease (CKD) progression in routine clinical practice in rural primary care setting. Methods: After enrolment, patients with stages 3 to 4 CKD patients from five district hospitals in a northern province of Thailand (400 km from Bangkok) received integrated care comprising hospital multidisciplinary care and home visits by community care teams. Clinical characteristics and biochemical data were collected at baseline and every 3‐month interval thereafter for 36 months. The primary outcome was the rate of estimated glomerular filtration rate (eGFR) decline. Results: Nine hundred and fourteen stage −3 and − 4 CKD patients were enrolled. The mean age of our cohort was 62 years. Diabetic kidney disease (DKD) was the main cause of CKD (53%) whereas hypertension was the most common co‐morbidity (92%). The mean rate of eGFR decline was −0.92 mL/min/1.73 m2/year. The rate of eGFR decline among patients with DKD was about three times faster than patients without DKD. Patients with higher blood pressure, metabolic acidosis, proteinuria or anaemia had a faster rate of eGFR decline. Conclusion: This integrated care model at the community level was effective in delaying CKD progression in routine clinical practice situation. SUMMARY AT A GLANCE: This report of a prospective cohort study shows the effectiveness of an integrated care model on delaying CKD progression in a Thai rural primary care setting. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Background: Although the prevalence of obesity and metabolic syndrome (MetS) among dialysis patients has been exceeding than general population, little is known regarding obesity and MetS in non-dialysis chronic kidney disease (CKD). We aimed to find the magnitude of obesity and MetS and their associations with impaired renal function among type 2 diabetes mellitus (T2DM) patients. Methods: A national survey of T2DM patients was collected in the Thai National Health Security Office database during 2014–5. The sampling frame was designated as distinct geographic regions throughout the country. A stratified two-stage cluster sampling was used to select the study population. Anthropometry and 12-hour fasting blood samples were obtained by trained personnel. BMI of ≥25 kg/m2 was classified as obesity. MetS was defined as having elevated waist circumference (>90 and >80 cm in men and women, respectively) plus any two of the followings: triglyceride ≥150 mg/dL, HDL-C <40 in men or <50 mg/dL in women, blood pressure ≥130/85 mmHg, and fasting blood sugar ≥100 mg/dL. CKD was defined as an impaired renal function (eGFR <60 mL/min/1.73m2 according to the CKD-EPI equation). Logistic regression analysis was performed to examine the relationship between obesity and MetS with the presence of CKD. Results: A total of 32,616 diabetic patients were finally recruited from 997 hospitals. The mean age was 61.5±10.9 years with 67.5% women. Of the participants, 35.4% were CKD patients. The prevalence of obesity was 46.5% in CKD and 54.1% in non-CKD patients with T2DM (p<0.001). In contrast, the prevalence of MetS in CKD patients was higher than their non-CKD counterparts (71.3 vs 68.8%, p<0.001). Moreover, there was an association between the prevalence of MetS with CKD stage from 3a to 5 (70.1, 72.3, 73.4, and 72.7%, respectively, p trend = 0.02). MetS, but not obesity, had a significant association with CKD in T2DM patients after adjusting for age, sex, and comorbidities [OR 1.14; 95% CI 1.06–1.22, p<0.001]. When stratified by each component of MetS, only high serum triglyceride and low HDL-C levels were increased in patients with CKD stage 4 and 5 compared with CKD stage 3 (p<0.001) and had a significant relationship with impaired renal function. Conclusion: There were relatively high prevalences of both obesity and MetS in T2DM patients. A higher prevalence of MetS, but lower prevalence of obesity, was observed among diabetic CKD group compared with their non-CKD counterparts. MetS, as a surrogate of insulin resistance, appeared to be more important than obesity in the development of impaired renal function in diabetic population. [ABSTRACT FROM AUTHOR]

Background: In developing countries, renal specialists are scarce and physician-to-patient contact time is limited. While conventional hospital-based, physician-oriented approach has been the main focus of chronic kidney disease (CKD) care, a comprehensive multidisciplinary health care program (Integrated CKD Care) has been introduced as an alternate intervention to delay CKD progression in a community population. The main objective is to assess effectiveness of Integrated CKD Care in delaying CKD progression.Methods: We carried out a community-based, cluster randomized controlled trial. Four hundred forty-two stage 3-4 CKD patients were enrolled. In addition to the standard treatments provided to both groups, the patients in the intervention group also received "Integrated CKD Care". This was delivered by a multidisciplinary team of hospital staff in conjunction with a community CKD care network (subdistrict healthcare officers and village health volunteers) to provide group counseling during each hospital visit and quarterly home visits to monitor compliance with the treatment. Duration of the study was 2 years. The primary outcome was difference of mean eGFR between the intervention and the control groups over the study period.Results: The mean difference of eGFR over time in the intervention group was significantly lower than the control group by 2.74 ml/min/1.73 m2 (95%CI 0.60-4.50, p = 0.009). Seventy composite clinical endpoints were reported during the study period with significantly different incidences between the control and the intervention groups (119.1 versus 69.4 per 1000 person-years; hazard ratio (HR) 0.59, 95% CI 0.4-0.9, p = 0.03).Conclusion: Integrated CKD Care can delay CKD progression in resource-limited settings.Trial Registration: ( NCT01978951 ). Prospectively registered as of December 8, 2012. [ABSTRACT FROM AUTHOR]

Background In developing countries, accessibility to specialists, and physician to patient contact time is limited. In Thailand, A unique community health service is provided by subdistrict health care officers and Village Health Volunteers (VHVs). If the personnel were trained on proper chronic kidney disease (CKD) care, CKD progression would be delayed. Methods/Design We conducted a community-based, cluster randomized controlled trial at Kamphaeng Phet Province, located about 400 kilometers north of Bangkok. Two out of eleven districts of the province were randomly selected. Approximatly 500 stage 3-4 CKD patients from 2 districts were enrolled. Patients in both groups will be treated with standard guidelines. The patients in intervention group were provided the additional treatments by multidisciplinary team in conjunction with community CKD care network (subdistrict health care officers and VHVs) which will provide group counseling during each hospital visit and quarterly home visits to monitor dietary protein and sodium intake, blood pressure measurement and drug compliance. Duration of the study is 2 years. The primary outcome is the difference of rate of eGFR decline. The secondary outcomes are laboratory parameters and incidence of clinical endpoints such as mortality rate and cardiovascular events, end-stage renal disease (ESRD), etc. Discussion Insights of this study may set forth a new standard of community-based CKD care. [ABSTRACT FROM AUTHOR]

Background: The Asian Forum of Chronic Kidney Disease Initiative started in 2007 in Hamamatsu, Japan when delegates from 16 countries joined together to facilitate collaboration in studying chronic kidney disease (CKD) in the Asia–Pacific region. Based on the outcome of the first meeting, the second meeting was organized as a consensus conference to frame the most relevant issues, and develop research recommendations and action plan. Proceedings: The meeting was held on 4 May 2008 as a pre-conference meeting to the 11th Asian Pacific Congress of Nephrology in Kuala Lumpur. This meeting consisted of three sessions: Session I was dedicated to the estimation of glomerular filtration rate and the standardization of serum creatinine measurements. Session II discussed specific considerations in the aetiology of and risk factors for end-stage renal disease in Asia. We concluded that there were regional specific problems that might lead to a very high prevalence of end-stage renal disease. Session III discussed the issue of facilitation of coordination and integration of the CKD initiative between developed and developing countries in the Asia–Pacific region. Conclusion: The following action plans were formulated: (i) validating the existing global estimated glomerular filtration rate equation or creating a new one using serum creatinine standardized by a central laboratory; (ii) establishing a pan-Asian CKD registry to facilitate risk analysis of CKD and its comorbidities; (iii) adapting existing clinical practice guidelines for CKD detection and management to address specific problems in this region; and (iv) working closely with other international professional organizations to promote manpower development and education in different aspects of CKD in developing countries. [ABSTRACT FROM AUTHOR]

A chronic kidney disease (CKD) causes uremic toxin accumulation and gut dysbiosis, which further induces gut leakage and worsening CKD. Lipopolysaccharide (LPS) of Gram-negative bacteria and (1➔3)-β-D-glucan (BG) of fungi are the two most abundant gut microbial molecules. Due to limited data on the impact of intestinal fungi in CKD mouse models, the influences of gut fungi and Lacticaseibacillus rhamnosus L34 (L34) on CKD were investigated using oral C. albicans-administered 5/6 nephrectomy (5/6Nx) mice. At 16 weeks post-5/6Nx, Candida-5/6Nx mice demonstrated an increase in proteinuria, serum BG, serum cytokines (tumor necrotic factor-α; TNF-α and interleukin-6), alanine transaminase (ALT), and level of fecal dysbiosis (Proteobacteria on fecal microbiome) when compared to non-Candida-5/6Nx. However, serum creatinine, renal fibrosis, or gut barrier defect (FITC-dextran assay and endotoxemia) remained comparable between Candida- versus non-Candida-5/6Nx. The probiotics L34 attenuated several parameters in Candida-5/6Nx mice, including fecal dysbiosis (Proteobacteria and Bacteroides), gut leakage (fluorescein isothiocyanate (FITC)-dextran), gut-derived uremic toxin (trimethylamine-N-oxide; TMAO) and indoxyl sulfate; IS), cytokines, and ALT. In vitro, IS combined with LPS with or without BG enhanced the injury on Caco-2 enterocytes (transepithelial electrical resistance and FITC-dextran permeability) and bone marrow-derived macrophages (supernatant cytokines (TNF-α and interleukin-1 β; IL-1β) and inflammatory genes (TNF-α, IL-1β, aryl hydrocarbon receptor, and nuclear factor-κB)), compared with non-IS activation. These injuries were attenuated by the probiotics condition media. In conclusion, Candida administration worsens kidney damage in 5/6Nx mice through systemic inflammation, partly from gut dysbiosis-induced uremic toxins, which were attenuated by the probiotics. The additive effects on cell injury from uremic toxin (IS) and microbial molecules (LPS and BG) on enterocytes and macrophages might be an important underlying mechanism. [ABSTRACT FROM AUTHOR]

Experience with prevention programs in Thailand. Thailand is a developing country with a population of 62 million. It is estimated to have 1.6 million stage 3 or higher chronic kidney disease (CKD) patients. With limited funding for dialysis support, prevention of renal disease progression is mandatory and urgently needed. The Nephrology Society of Thailand has conducted a survey among Thai nephrologists. The data were analyzed, and a multidisciplinary team approach was introduced to make patients more informed about CKD and more compliant with dietary prescription. The survey showed that the majority of Thai nephrologists know about CKD guidelines. They regularly employed several modes of drug therapy and appropriate target of blood pressure control. However, only 38% and 5% of nephrologists used multidisciplinary team approach and knew how to calculate dietary protein intake, respectively, in CKD patients. To facilitate dietary counseling and care team approach, we invented several dietary record forms (in Thai), Thai food exchange list, 7-day low-protein Thai food menu, and several patient education guidebooks. We also set 1-day lecture tour courses for physicians, nurses, and dieticians in various parts of the country. At our own institute, we followed 17 CKD patients for 4 years: the creatinine clearance (CCr) and glomerular filtration rate (GFR) were 37.5 ± 5.5 and 24.4 ± 4.3 mL/min, respectively, at the beginning, and were 35.7 ± 4.5 and 25.0 ± 3.5 mL/min, respectively, 4 years thereafter. The rates of Ccr and GFR decline were –0.5 ± 0.9 mL/min/year and 0.2 ± 0.6 mL/min/year, respectively. A combination of appropriate drug and dietary therapy by employing a multidisciplinary team approach can effectively delay renal disease progression. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]