Dialysis Care and Dialysis Funding in Asia.

Asia is the largest and most populated continent in the world, with a high burden of kidney failure. In this Policy Forum article, we explore dialysis care and dialysis funding in 17 countries in Asia, describing conditions in both developed and developing nations across the region. In 13 of the 17 countries surveyed, diabetes is the most common cause of kidney failure. Due to great variation in gross domestic product per capita across Asian countries, disparities in the provision of kidney replacement therapy (KRT) exist both within and between countries. A number of Asian nations have satisfactory access to KRT and have comprehensive KRT registries to help inform practices, but some do not, particularly among low- and low-to-middle-income countries. Given these differences, we describe the economic status, burden of kidney failure, and cost of KRT across the different modalities to both governments and patients and how changes in health policy over time affect outcomes. Emerging trends suggest that more affluent nations and those with universal health care or access to insurance have much higher prevalent dialysis and transplantation rates, while in less affluent nations, dialysis access may be limited and when available, provided less frequently than optimal. These trends are also reflected by an association between nephrologist prevalence and individual nations' incomes and a disparity in the number of nephrologists per million population and per thousand KRT patients.

Assessment of safety and intranasal neutralizing antibodies of HPMC-based human anti-SARS-CoV-2 IgG1 nasal spray in healthy volunteers.

An HPMC-based nasal spray solution containing human IgG1 antibodies against SARS-CoV-2 (nasal antibody spray or NAS) was developed to strengthen COVID-19 management. NAS exhibited potent broadly neutralizing activities against SARS-CoV-2 with PVNT50 values ranging from 0.0035 to 3.1997 µg/ml for the following variants of concern (ranked from lowest to highest): Alpha, Beta, Gamma, ancestral, Delta, Omicron BA.1, BA.2, BA.4/5, and BA.2.75. Biocompatibility assessment showed no potential biological risks. Intranasal NAS administration in rats showed no circulatory presence of human IgG1 anti-SARS-CoV-2 antibodies within 120 h. A double-blind, randomized, placebo-controlled trial (NCT05358873) was conducted on 36 healthy volunteers who received either NAS or a normal saline nasal spray. Safety of the thrice-daily intranasal administration for 7 days was assessed using nasal sinuscopy, adverse event recording, and self-reporting questionnaires. NAS was well tolerated, with no significant adverse effects during the 14 days of the study. The SARS-CoV-2 neutralizing antibodies were detected based on the signal inhibition percent (SIP) in nasal fluids pre- and post-administration using a SARS-CoV-2 surrogate virus neutralization test. SIP values in nasal fluids collected immediately or 6 h after NAS application were significantly increased from baseline for all three variants tested, including ancestral, Delta, and Omicron BA.2. In conclusion, NAS was safe for intranasal use in humans to increase neutralizing antibodies in nasal fluids that lasted at least 6 h.

N-terminal-pro-brain natriuretic peptide for the differential diagnosis of hypovolemia vs. euvolemia in hyponatremic patients.

BACKGROUND: Hyponatremia (serum sodium < 135 mEq/L) is the most common electrolyte abnormality in hospital and has impact on patient morbidity and mortality. The accuracy of volume status assessment is a major problem for the treatment planning especially to discriminate mild hypovolemic from euvolemic patients. OBJECTIVE: To examine the relationship between plasma N-Terminal-pro-Brain Natriuretic Peptide (NT-pro-BNP) level and extracellular water (ECW) status during the treatment of hyponatremia, as well as the cut-off value of plasma NT-pro-BNP in the differential diagnosis of volume status in hypovolemic vs. euvolemic hyponatremic patients. MATERIAL AND METHOD: Hyponatremic patients without clinical hypervolemia in Rajavithi Hospital were divided into the hypovolemic group and the euvolemic group according to ECW volume determined by bioimpedance analysis (BIA). Serum sodium, plasma NT-pro-BNP and ECW were assessed at the beginning, at the half correction of hyponatremia and at the end of treatment. RESULTS: Of the 26 patients, 18 (69.2%) were hypovolemic and 8 (30.8%) were euvolemic. Before treatment, NT-pro-BNP levels of the patients with hypovolemia was significantly lower than the patients with euvolemia [median (min, max)] (pg/mL) of hypovolemic vs. euvolemic group [114 (21, 6,803) vs. 1,509 (538, 8,541)] respectively (p < 0.001) and NT-pro-BNP levels change in the similar direction as ECW volume during the treatment. The best cut-off value of plasma NT-pro-BNP level to distinguish hypovolemic from euvolemic hyponatremia was 518 pg/ml with the sensitivity of 94.4% and the specificity of 100%. CONCLUSION: Plasma NT-pro-BNP levels provide objective information with respection to volume status in hyponatremia patients and can be used in clinical diagnosis of hypovolemic vs. euvolemic hyponatremic hyponatremia.

An open label, randomized controlled study of oral calcitriol for the treatment of proteinuria in patients with diabetic kidney disease.

BACKGROUND: The progression of diabetic kidney disease (DKD) is highly correlated with proteinuria. Previous studies have suggested that vitamin D treatment may reduce proteinuria and has the potential to delay the progression of renal disease. OBJECTIVE: To evaluate efficacy of oral calcitriol to decrease proteinuria in type 2 diabetic mellitus (T2DM) patients with DKD. MATERIAL AND METHOD: In this 16-week, open label, prospective, randomized controlled study, 91 patients with T2DM with estimated glomerular filtration rate (eGFR) greater than 15 ml/min/1.73 m2 and urine protein to creatinine ratio (UPCR) greater than 1 g/g were enrolled. They were randomly assigned to receive either oral calcitriol 0.5 mcg twice weekly (n = 46) or without oral calcitriol (n = 45). The primary outcome was determined by the change of UPCR from baseline after 16 weeks of treatment of both groups. RESULTS: At randomization, the mean UPCR was 3.7 + 2.2 g/g in the calcitriol group and 3.4 +/- 2.1 g/g in the control group. The mean UPCR at 16-week follow-up was 2.9 +/- 1.7 g/g in the calcitriol group and 3.5 +/- 2.3 g/g in the control group. Percent changes in UPCR from baseline to the last evaluation in the calcitriol and control groups were -18.7% and +9.9% (p < 0.01) respectively. Patients with 30% or more decrement in proteinuria occurred 43.5% of the time in the calcitriol group and 11.1% in the control group (p < 0.01). The eGFR and blood pressure did not differ significantly between the two groups. No serious adverse side effects were noted in either group. CONCLUSION: Calcitriol treatment can reduce proteinuria in patients with DKD without serious adverse events.

Risk factors of infectious peritonitis of CAPD patients in Rajavithi Hospital.

OBJECTIVE: Continuous ambulatory peritoneal dialysis (CAPD) is a renal replacement therapy for end stage renal disease (ESRD) patients. Peritoneal infection, peritonitis is a major cause of death and technical failure in ESRD patients receiving CAPD treatment. Previous studies demonstrated that lower serum albumin, higher body mass index, and diabetic kidney disease were associated with increase in incidence of peritonitis. However the demographics of the patients in the Rajavithi hospital such as race, gender, age, socioeconomic status and various other factors were different from the patients in the previous studies. The present study was conducted to investigate the risk factors of peritonitis, causative organisms, and route of infection among CAPD patients in Rajavithi Hospital. MATERIAL AND METHOD: This is a retrospective descriptive study. All patients in the present study are ESRD patients who received CAPD treatment during March 2009 to February 2011 and adhered with the treatment for at least 1 year. The patients were divided into two groups 1) the patients who got infectious peritonitis within 1 year after catheter implantation and 2) the patients who did not get or got infectious peritonitis after 1 years. The medical records were reviewed and the data were analyzed to identify the risk factors of peritonitis, frequency of causative organisms, and the route of infection. RESULTS: Of 27 patients, 16 patients (59.3%) had peritonitis within the first year, and 11 patients (40.7%) had no peritonitis or had peritonitis after the first year. The risk factors associated with peritonitis were diabetes (62.5 % in patients with peritonitis within first year vs. 18.2% in the patients who had no peritonitis or had peritonitis after the first year, p = 0.047) and higher blood sugar level (139.5 +/- 34.6 mg/dl in patients with peritonitis within first year vs. 115.9 +/- 23.4 mg/dl 18.2% in the patients who had no peritonitis or had peritonitis after the first year, p = 0.011). Transluminal peritoneal catheter route was the route of infection in every subject in the present study. The major causative agents were gram-positive bacteria. CONCLUSION: Diabetic kidney disease and high fasting blood sugar were the risk factors of peritonitis and trans-luminal peritoneal catheter are the major route of infection in the present study. Therefore, good blood sugar control and strict adherence with sterile technique for peritoneal dialysis would decrease the incidence of peritonitis in CAPD patients.

Molecular correlates of renal function in kidney transplant biopsies.

The molecular changes in the parenchyma that reflect disturbances in the function of kidney transplants are unknown. We studied the relationships among histopathology, gene expression, and renal function in 146 human kidney transplant biopsies performed for clinical indications. Impaired function (estimated GFR) correlated with tubular atrophy and fibrosis but not with inflammation or rejection. Functional deterioration before biopsy correlated with inflammation and tubulitis and was greater in cases of rejection. Microarray analysis revealed a correlation between impaired renal function and altered expression of sets of transcripts consistent with tissue injury but not with those consistent with cytotoxic T cell infiltration or IFN-gamma effects. Multivariate analysis of clinical variables, histologic lesions, and transcript sets confirmed that expression of injury-related transcript sets independently correlated with renal function. Analysis of individual genes confirmed that the transcripts with the greatest positive or negative correlations with renal function were those suggestive of response to injury and parenchymal dedifferentiation not inflammation. We defined new sets of genes based on individual transcripts that correlated with renal function, and these highly correlated with the previously developed injury sets and with atrophy and fibrosis. Thus, in biopsies performed for clinical reasons, functional disturbances are reflected in transcriptome changes representing tissue injury and dedifferentiation but not the inflammatory burden.

Global case studies for chronic kidney disease/end-stage kidney disease care.

The prevalence of chronic kidney disease and its risk factors is increasing worldwide, and the rapid rise in global need for end-stage kidney disease care is a major challenge for health systems, particularly in low- and middle-income countries. Countries are responding to the challenge of end-stage kidney disease in different ways, with variable provision of the components of a kidney care strategy, including effective prevention, detection, conservative care, kidney transplantation, and an appropriate mix of dialysis modalities. This collection of case studies is from 15 countries from around the world and offers valuable learning examples from a variety of contexts. The variability in approaches may be explained by country differences in burden of disease, available human or financial resources, income status, and cost structures. In addition, cultural considerations, political context, and competing interests from other stakeholders must be considered. Although the approaches taken have often varied substantially, a common theme is the potential benefits of multistakeholder engagement aimed at improving the availability and scope of integrated kidney care.

Challenges for sustainable end-stage kidney disease care in low-middle-income countries: the problem of the workforce.

Prevention and early detection of kidney diseases in adults and children should be a priority for any government health department. This is particularly pertinent in the low-middle-income countries, mostly in Asia, Africa, Latin America, and the Caribbean, where up to 7 million people die because of lack of end-stage kidney disease treatment. The nephrology workforce (nurses, technicians, and doctors) is limited in these countries and expanding the size and expertise of the workforce is essential to permit expansion of treatment for both chronic kidney disease and end-stage kidney disease. To achieve this will require sustained action and commitment from governments, academic medical centers, local nephrology societies, and the international nephrology community.

Endothelial gene expression in kidney transplants with alloantibody indicates antibody-mediated damage despite lack of C4d staining.

Anti-HLA alloantibody is a risk factor for graft loss, but does not indicate which kidneys are experiencing antibody-mediated rejection (ABMR). C4d staining in biopsies is specific for ABMR but insensitive. We hypothesized that altered expression of endothelial genes due to alloantibody acting on the microcirculation would be sensitive indicator of ABMR. We identified 119 endothelial-associated transcripts (ENDATs) from literature, and studied their expression by microarrays in 173 renal allograft biopsies for cause. Mean ENDAT expression was increased in all rejection but was higher in ABMR than in T-cell-mediated rejection and correlated with histopathologic lesions of ABMR, and alloantibody. Many individual ENDATs were increased in ABMR and predicted graft loss. Kidneys with high ENDATs and antibody showed increased lesions of ABMR and worse prognosis in comparison to controls. Only 40% of kidneys with high ENDAT expression and chronic ABMR or graft loss were diagnosed by C4d positivity. High ENDAT expression with antibody predicts graft loss with higher sensitivity (77% vs. 31%) and slightly lower specificity (71% vs. 94%) than C4d. The results were validated in independent set of 82 kidneys. High renal endothelial transcript expression in patients with alloantibody is indicator of active antibody-mediated allograft damage and poor graft outcome.

Effect of diltiazem on the pharmacokinetics of microemulsion cyclosporine A in renal transplantation.

OBJECTIVE: Diltiazem might be used as a cyclosporine A (CsA)-sparing agent. There is evidence that CsA (C2) level is the best single point blood sampling for monitoring the CsA level. The authors, therefore, studied the effect of diltiazem on the pharmacokinetics (PK) of CsA, including C2, in renal transplant patients. MATERIAL AND METHOD: Twenty-five CsA-treated renal transplant patients, with neither diseases nor agents that alter the PK of CsA, were enrolled in the present study. The PK of CsA was studied in all patients before and 2 weeks after taking diltiazem. RESULTS: The area under the concentration-time curve (AUC) of CsA was obtained by 2 methods, AUC0-4 and AUC0-12. Before taking diltiazem, the correlation (r) between C0 with AUC0-4 and C0 with AUC0-12 were 0.799 and 0.871, respectively (p = 0.01), r between C2 with AUC0-4 and C2 with AUC0-12 were 0.988 and 0.956, respectively (p = 0.01). Time to maximum concentration (Tmax) of CsA was at 1.5 hr (1.5-4.0 hr) [median (range)]. After two weeks of taking diltiazem, r between C0 with AUC0-4 and C0 with AUC0-12 were 0.577 and 0.784, respectively (p = 0.01), r between C2 with AUC0-4 and C2 with AUC0-12 were 0.988 and 0.896, respectively (p = 0.01). Tmax of CsA was at 1.5 hr (1.5-4.0 hr) [median (range)]. The dosage of CsA could be reduced by 25.8% to maintain the same levels of C0 and C2 in the same patients after taking diltiazem. CONCLUSION: Diltiazem slightly altered the correlation between C2 with AUC of CsA. This indicates that C2 is the best single point blood sampling to monitor the therapeutic levels of CsA in renal transplant patients who are taking diltiazem.

Respiratory complication of tsunami victims in Phuket and Phang-Nga.

In the present report the authors describe the clinical and laboratory findings of 26 tsunami victims admitted to the Phuket and the Takua Pa Hospital. Patients were classified into 4 groups of severity. class 1, baseline examination negative (n = 1); class 2, baseline examination positive but mechanical ventilation not needed on admission (n = 15); class 3, mechanical ventilation required on admission (n = 9); class 4, cardiopulmonary arrest (n = 1). On admission, 21/23 patients had fever of > 37.5 C. 3/10 patients had hypernatremia and 7/10 cases had metabolic acidosis. The radiological manifestation varied from focal disease to diffuse infiltrations, either reticulonodular or patchy lesions. There were 3 clinical courses among diffuse diseases: 1) diffuse infiltrations and progression 3 cases 2) diffuse infiltration, early regression followed by progression 2 cases 3) diffuse infiltration and steady regression 5 cases. Late complications comprised of pneumothorax/pneumomediastinum (n = 5) and bacterial pneumonia (n = 18). The authors got culture data in 9 patients, most of them were infected with aerobic gram -ve bacteria and 2 of them were B. pseudomallei. The prognosis in the tsunami related medical illness was favorable. Only 2 patients (7.7%) died in the present study.

Metabolic Syndrome in Thai Renal Transplant Recipients: A Multicenter Study.

BACKGROUND Many renal transplant recipients develop complications such as obesity, posttransplantation diabetes mellitus, and dyslipidemia. There have been few studies of metabolic syndrome (MS) in Asian renal transplant recipients. MATERIAL AND METHODS This cross-sectional study was performed in 303 patients in 5 transplant centers in Bangkok, Thailand. The diagnosis of MS was based on the criteria of the modified NCEP-ATPIII, and chronic allograft dysfunction was defined as estimated glomerular filtration rate (eGFR) <60 mL/min/1.73 m^2. RESULTS Of 303 recipients, MS was diagnosed in 94 cases (31.0%) and the prevalence of MS in the first 3 years and after 3 years posttransplantation were 21.4% and 34.7% (P=0.042), respectively. There was an association between advanced age and chronic allograft dysfunction and higher prevalence of MS. Regarding non-anti-hypertensive and non-hypoglycemic medications, m-TOR inhibitor (odds ratio [OR], 2.14; 95% CI, 1.02-4.5) was associated with the prevalence of MS. Multivariate analysis revealed MS was associated with the use of beta-blockers (OR, 3.17; 95% CI, 1.88-5.32). Patients with no MS components had 26.9% prevalence of chronic allograft dysfunction and patients with higher numbers of MS components had 87.5% prevalence of chronic allograft dysfunction, which was significantly different (P=0.022). CONCLUSIONS Our study revealed that the prevalence of MS was higher in patients with higher numbers of MS components, especially after 3 years posttransplantation. Presence of more components of MS was associated with worse renal function in renal transplant recipients.