Practice of dialysis access interventional nephrology procedures in the Asia-Pacific region: Getting lay of the land.

AIM: This cross-sectional survey aimed to determine the prevalence of Interventional Nephrology (IN) practice amongst nephrologists in the Asia-Pacific Region (APR), specifically related to dialysis access (DA). METHODS: The Association of VA and intervenTionAl Renal physicians (AVATAR) Foundation from India conducted a multinational online survey amongst nephrologists from the Asia-Pacific to determine the practice of IN in the planning, creation, and management of dialysis access. The treatment modalities, manpower and equipment availability, monthly cost of treatment, specifics of dialysis access interventions, and challenges in the training and practice of IN by nephrologists were included in the survey. RESULTS: Twenty-one countries from the APR participated in the survey. Nephrologists from 18 (85.7%) countries reported performing at least one of the basic dialysis access-related IN procedures, primarily the placement of non-tunnelled central catheters (n-TCC; 71.5%). Only 10 countries (47.6%) reported having an average of <4% of nephrologists performing any of the advanced IN access procedures, the most common being the placement of a peritoneal dialysis (PD) catheter (20%). Lack of formal training (57.14%), time (42.8%), incentive (38%), institutional support (38%), medico-legal protection (28.6%), and prohibitive cost (23.8%) were the main challenges to practice IN. The primary obstacles to implementing the IN training were a lack of funding and skilled personnel. CONCLUSION: The practice of dialysis access-related IN in APR is inadequate, mostly due to a lack of training, backup support, and economic constraints, whereas training in access-related IN is constrained by a lack of a skilled workforce and finances.

Five-Year Survival Rate of Patients with End-Stage Renal Disease on Continuous Ambulatory Peritoneal Dialysis (CAPD) at Malang CAPD Center, Indonesia.

BACKGROUND: Continuous Ambulatory Peritoneal Dialysis (CAPD) is an alternative therapy for renal replacement in patients with kidney failure in developing countries such as Indonesia. The CAPD program in Malang Indonesia has been running since 2010. Until now, there has been little research on the mortality of CAPD therapy in Indonesia. We aimed to provide report on the characteristics and 5-year survival of CAPD therapy in patients with end-stage renal disease (ESRD) in developing countries like Indonesia. METHODS: We conducted a retrospective cohort study involving 674 patients with end-stage renal disease receiving CAPD therapy from the medical records of the CAPD Center RSUD Dr. Saiful Anwar from August 2014 to July 2020. The 5-year survival rate was analyzed using Kaplan-Meier, and the hazard ratio was analyzed using Cox regression. RESULTS: Of 674 patients with end-stage renal disease who underwent CAPD, 63.2% survived up to 5 years, with general survival rates at 1, 3, and 5 years of 80%, 60%, and 52%, respectively. The 3-year survival rate for patients with end-stage renal disease and comorbid hypertension was 80%, while it was 10% for patients with comorbid hypertension and type II diabetes mellitus. The hazard ratio for patients with end-stage renal disease who had comorbid hypertension and type II diabetes mellitus was 8.4 (95% CI = 6.36-11.21). CONCLUSION: Patients with end-stage renal disease who receive CAPD therapy have a favorable 5 years survival rate. Patients with end-stage renal disease on CAPD therapy who have comorbid hypertension and type II diabetes mellitus have a lower survival rate than patients with comorbid hypertension alone.

Association Between the Effectiveness and Immunogenicity of Inactivated SARS-CoV2 Vaccine (CoronaVac) with the Presence of Hypertension among Health Care Workers.

OBJECTIVE: This study aimed to observe the association between the presence of hypertension with Covid-19 vaccine effectiveness among healthcare workers who received CoronaVac vaccination. METHODS: We conducted a prospective cohort study in Saiful Anwar General Hospital, Malang, Indonesia on 155 healthcare workers aged 18-59 years old who already received twice of the CoronaVac (Sinovac Life Science, Beijing, China) injection with 14-day intervals. Hypertension was diagnosed according to the 2020 International Society of Hypertension. Subjects were monitored for six months. The primary outcome was the rate of Covid-19 diagnosed by the pharyngeal swab for the real-time reverse transcription-polymerase chain reaction (RT-PCR) examination. The secondary endpoints were: (1) severity of Covid-19 among infected participants; (2) rate of hospitalizations; and (3) anti-SRBD antibody levels measured by ECLIA. RESULTS: Among 155 participants, 18.7% of them were diagnosed with hypertension, and 31.0% had the desirable BP target according to the current guidelines. Subjects with hypertension, especially those with uncontrolled blood pressure, had a higher incidence of Covid-19 infection than subjects without hypertension. Subjects with symptomatic Covid-19 and hospitalized because of Covid-19 were higher in participants with hypertension. The anti-SRBD antibody levels were lower in the second month after CoronaVac vaccination in hypertensive subjects. In contrast, comparable anti-SRBD levels were seen from both groups at sixth months after vaccination. CONCLUSION: Hypertension was associated with lower vaccine effectiveness in healthcare workers. Subjects with hypertension had a higher risk of being infected with Covid-19 despite getting a complete dose of vaccination and lower antibody production.

Interventional nephrology and vascular access practice: A perspective from South and Southeast Asia.

South and Southeast Asia is the most populated, heterogeneous part of the world. The Association of Vascular Access and InTerventionAl Renal physicians (AVATAR Foundation), India, gathered trends on epidemiology and Interventional Nephrology (IN) for this region. The countries were divided as upper-middle- and higher-income countries as Group-1 and lower and lower-middle-income countries as Group-2. Forty-three percent and 70% patients in the Group 1 and 2 countries had unplanned hemodialysis (HD) initiation. Among the incident HD patients, the dominant Vascular Access (VA) was non-tunneled central catheter (non-TCC) in 70% of Group 2 and tunneled central catheter (TCC) in 32.5% in Group 1 countries. Arterio-Venous Fistula (AVF) in the incident HD patients was observed in 24.5% and 35% of patients in Group-2 and Group-1, respectively. Eight percent and 68.7% of the prevalent HD patients in Group-2 and Group-1 received HD through an AVF respectively. Nephrologists performing any IN procedure were 90% and 60% in Group-2 and Group 1, respectively. The common procedures performed by nephrologists include renal biopsy (93.3%), peritoneal dialysis (PD) catheter insertion (80%), TCC (66.7%) and non-TCC (100%). Constraints for IN include lack of time (73.3%), lack of back-up (40%), lack of training (73.3%), economic issues (33.3%), medico-legal problems (46.6%), no incentive (20%), other interests (46.6%) and institution not supportive (26%). Routine VA surveillance is performed in 12.5% and 83.3% of Group-2 and Group-1, respectively. To conclude, non-TCC and TCC are the most common vascular access in incident HD patients in Group-2 and Group-1, respectively. Lack of training, back-up support and economic constraints were main constraints for IN growth in Group-2 countries.

Peritoneal dialysis: Status report in South and South East Asia.

BACKGROUND: Peritoneal dialysis (PD) as a modality of kidney replacement therapy (KRT) is largely underutilized globally. We analyzed PD utilization, impact of economic status, projected growth and impact of state policy(s) on PD growth in South Asia and Southeast Asia (SA&SEA) region. METHODS: The National Nephrology Societies of the region responded to a questionnaire on KRT practices. The responses were based on the latest registry data, acceptable community-based studies and societal perceptions. The representative countries were divided into high income and higher-middle income (HI & HMI) and low income and lower-middle income (LI & LMI) groups. RESULTS: Data provided by 15 countries showed almost similar percentage of GDP as health expenditure (4%-7%). But there was a significant difference in per capita income (HI & HMI -US$ 28 129 vs. LI & LMI - US$ 1710.2) between the groups. Even after having no significant difference in monthly cost of haemodialysis (HD) and PD in LI & LMI countries, they have poorer PD utilization as compared to HI & HMI countries (3.4% vs. 10.1%); the reason being lack of formal training/incentives and time constraints for the nephrologist while lack of reimbursement and poor general awareness of modalities has been a snag for the patients. The region expects ≥10% PD growth in the near future. Hong Kong and Thailand with 'PD first' policy have the highest PD utilization. CONCLUSION: Important deterrents to PD underutilization were lack of PD centric policies, lackadaisical patient/physician's attitude, lack of structured patient awareness programs, formal training programs and affordability.

Impact of National Economy and Policies on End-Stage Kidney Care in South Asia and Southeast Asia.

BACKGROUND: The association between economic status and kidney disease is incompletely explored even in countries with higher economy (HE); the situation is complex in lower economies (LE) of South Asia and Southeast Asia (SA and SEA). METHODS: Fifteen countries of SA and SEA categorized as HE and LE, represented by the representatives of the national nephrology societies, participated in this questionnaire and interview-based assessment of the impact of economic status on renal care. RESULTS: Average incidence and prevalence of end-stage kidney disease (ESKD) per million population (pmp) are 1.8 times and 3.3 times higher in HE. Hemodialysis is the main renal replacement therapy (RRT) (HE-68%, LE-63%). Funding of dialysis in HE is mainly by state (65%) or insurance bodies (30%); out of pocket expenses (OOPE) are high in LE (41%). Highest cost for hemodialysis is in Brunei and Singapore, and lowest in Myanmar and Nepal. Median number of dialysis machines/1000 ESKD population is 110 in HE and 53 in LE. Average number of machines/dialysis units in HE is 2.7 times higher than LE. The HE countries have 9 times more dialysis centers pmp (median HE-17, LE-02) and 16 times more nephrologist density (median HE-14.8 ppm, LE-0.94 ppm). Dialysis sessions >2/week is frequently followed in HE (84%) and <2/week in LE (64%). "On-demand" hemodialysis (<2 sessions/week) is prevalent in LE. Hemodialysis dropout rates at one year are lower in HE (12.3%; LE 53.4%), death being the major cause (HE-93.6%; LE-43.8%); renal transplants constitute 4% (Brunei) to 39% (Hong Kong) of the RRT in HE. ESKD burden is expected to increase >10% in all the HE countries except Taiwan, 10%-20% in the majority of LE countries. CONCLUSION: Economic disparity in SA and SEA is reflected by poor dialysis infrastructure and penetration, inadequate manpower, higher OOPE, higher dialysis dropout rates, and lesser renal transplantations in LE countries. Utility of RRT can be improved by state funding and better insurance coverage.

Aetiology, practice patterns and burden of end-stage kidney disease in South Asia and South-East Asia: A questionnaire-based survey.

AIM: There is paucity of data on the epidemiology of end-stage kidney disease (ESKD) from South Asia and South-East Asia. The objective of this study was to assess the aetiology, practice patterns and disease burden and growth of ESKD in the region comparing the economies. METHODS: The national nephrology societies of the region; responded to the questionnaire; based on latest registries, acceptable community-based studies and society perceptions. The countries in the region were classified into Group 1 (High|higher-middle-income) and Group 2 (lower|lowermiddle income). Student t-test, Mann-Whitney U test and Fisher's exact test were used for comparison. RESULTS: Fifteen countries provided the data. The average incidence of ESKD was estimated at 226.7 per million population (pmp), (Group 1 vs. Group 2, 305.8 vs. 167.8 pmp) and average prevalence at 940.8 pmp (Group 1 vs. Group 2, 1306 vs. 321 pmp). Group 1 countries had a higher incidence and prevalence of ESKD. Diabetes, hypertension and chronic glomerulonephritis were most common causes. The mean age in Group 2 was lower by a decade (Group 1 vs. Group 2-59.45 vs 47.7 years). CONCLUSION: Haemodialysis was the most common kidney replacement therapy in both groups and conservative management of ESKD was the second commonest available treatment option within Group 2. The disease burden was expected to grow >20% in 50% of Group 1 countries and 78% of Group 2 countries along with the parallel growth in haemodialysis and peritoneal dialysis.

Nitride oxide synthase 3 and klotho gene polymorphisms in the pathogenesis of chronic kidney disease and age-related cognitive impairment: a systematic review and meta-analysis.

Background: While it has been known that the development of chronic kidney disease (CKD) and age-related cognitive impairment involves several mediators, the evidence in clinical practice only reveals nitride oxide synthase (NOS) and klotho. However, the evidence for this topic is conflicted. The aim of this study was to assess the role of NOS and klotho single nucleotide polymorphisms (SNPs) in the pathogenesis of CKD and age-related cognitive impairment. Methods: We performed a meta-analysis during October to December 2019. Paper collection was performed in major scientific websites, and we extracted information of interest from each paper. Data were analyzed using a Z-test with either random or fixed effect model. Results: Our initial assessment identified NOS3 G894T, NOS3 T786C, NOS3 4b/4a, klotho ( KL) G395A, and KL C1818T as the gene candidate for our meta-analysis. Our pooled calculation revealed that NOS3 G894T was associated with the risk of both age-related cognitive impairment and CKD. Increased susceptibility to age-related cognitive impairment was observed in the GG genotype, and increased risk of CKD was found in patients with a single T allele and TT genotype for NOS3 nucleotide 894. For NOS3 4b/4a, increased risk of CKD was only found in 4a4a genotype. For NOS3 T786C, we failed to show the association with both CKD and age-related cognitive impairment. Subsequently, for KL G395A, A allele and GA genotype were found to correlate with increased susceptibility to CKD, while its correlation to age-related cognitive impairment was failed to clarify. For KL C1818T, our analysis failed to find the correlation with the risk of CKD. Conclusions: Our results reveal that the NOS3 G894T gene polymorphism has a crucial role in the pathogenesis of both CKD and age-related cognitive impairment.

Urinary Neutrophil Gelatinase-Associated Lipocalin to Monitor Lupus Nephritis Disease Activity.

BACKGROUND: This study was conducted to determine whether there is an association between urinary neutrophil gelatinase-associated lipocalin (uNGAL) and urinary transforming growth factor-ß1 (uTGF-ß1) with lupus nephritis (LN) disease activity. METHODS: Urine samples from 18 LN patients were collected every month for six months then examined for uNGAL, uTGF-ß1, and renal domain Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) score. RESULTS: The uNGAL levels were significantly different between active and inactive LN (P < 0.05). uTGF-ß1 levels were not different between active and inactive LN (P < 0.05). There was a significant correlation between uNGAL levels and renal domain SLEDAI score (r = 0.417, P < 0.05). There was no correlation between uTGF-ß1 levels and renal domain SLEDAI score (r = 0.031, P < 0.05). CONCLUSION: uNGAL is better than uTGF-ß1 for differentiation of active and inactive LN. uNGAL can be considered as a biomarker to monitor LN disease activity.

Analysis of urinary TGF-ß1, MCP-1, NGAL, and IL-17 as biomarkers for lupus nephritis.

This study was aimed to determine the diagnostic performance of transforming growth factor beta 1 (uTGF-ß1), monocyte chemoattractant protein-1 (uMCP-1), neutrophil gelatinase-associated lipocalin (uNGAL) and interleukin 17 (uIL-17) in LN. Seventy participants were studied, categorized into three groups: 38 severe LN (class III-IV LN patients); 12 mild LN (class I-II LN patients); and 20 control (healthy volunteers). Diagnosis of SLE was based on the 1997 ARA criteria. Class NL classified according to ISN/RPS 2004. uTGF-ß1, uMCP-1, uNGAL, uIL-17 levels were determined by ELISA, using spot urine. The level of uMCP-1 and uNGAL was significantly greater in severe or mild LN compared with control group (P<0.05). The level of uTGF-ß1 and uIL-17 was significantly higher in severe LN than that controls group (P<0.05). The AUC of uTGF-ß1, uMCP-1, uNGAL, uIL-17 was 66.50%; 86.90%; 87.50%; 71.70%, with the cut-off value of 27.13pg/ml; 1.54pg/ml; 446.30pg/ml; 36.62pg/ml. Only uNGAL showed a significant correlation with the activity (P=0.016; r=0.389) and chronicity indices (P=0.018; r=0.381). This study showed that uTGF-ß1, uMCP-1, uNGAL, uIL-17 levels were increased in LN. The AUC values for each biomarker are indicating a good diagnostic value. Urinary NGAL had the best sensitivity and specificity followed by uMCP-1, uIL-17 and uTGF-ß1. For combinations of two biomarkers, the best sensitivity and specificity were displayed by the combination of uTGF-ß1 & u-NGAL, followed by uMCP-1 & uNGAL.

Changes to signal peptide and the level of transforming growth factor- ß1 due to T869C polymorphism of TGF ß1 associated with lupus renal fibrosis.

Lupus Nephritis (LN) is a serious manifestation of lupus that can lead to End Stage Renal Disease (ESRD). Fibrosis is the main feature of ESRD, and it is likely influenced by Transforming Growth Factor Beta1 (TGFß1). The T869C gene polymorphism of TGFß1 is assumed to change the signal peptide, that has potential to interfere the urine production and renal protein expression of TGFß1. The influence of T869C gene polymorphism on TGFß1 production and renal fibrosis was evaluated in this study. Subjects were 45 patients LN with renal fibrosis and 45 participants without renal fibrosis as control, that were recruited from 2011 to 2013.Their urinary TGFß1 levels and TGFß1 gene polymorphisms were examined. All lupus patients underwent renal biopsy to assess their protein expression of TGFß1 in the renal tissue by immunohistochemistry and their renal fibrosis by morphometry and chronicity index. Changes in the signal peptide interaction with Signal Recognition Particle (SRP) and translocon of endoplasmic reticulum were analyzed by Bioinformatics. Levels of urinary and protein expression of TGFß1 increased in the LN with renal fibrosis group. There were significant differences in levels of urinary TGFß1 in T, C allele and TT, TC, CC genotypes between case and control groups. Furthermore, patients with C allele are 3.86 times more at risk of renal fibrosis than T allele. The C allele encodes proline, which stabilizes the interaction of the TGFß1 signal peptide with SRP and translocon, resulting in elevation of TGFß1 secretion. Our results indicated that T869C gene polymorphism of TGFß1 changes the signal peptide, that contributes to the production of urinary TGFß1 and affects renal fibrosis in lupus nephritis.

The Potential effect of G915C polymorphism in regulating TGF-ß1 transport into Endoplasmic Reticulum for cytokine production.

The TGF-ß1 cytokine concentration is known to be higher in nephritis with implied Lupus Nephritis severity. The production of TGF-ß1 cytokine is associated with G915C polymorphism. Therefore, it is of interest to study G915C polymorphism. The G915C polymorphism changes codon 25 which encodes arginine into proline in the signal peptide of TGF-ß1. The amino acid substitution affects signal peptide properties that may inhibit the transport of TGF-ß1 into the endoplasmic reticulum and eventually decline the cytokine production. Hence, the effect of G915C polymorphism on the properties of the signal peptide, the ability of TGF-ß1 transport into the endoplasmic reticulum and the concentrations of urinary TGF-ß1 in Lupus Nephritis patients was studied. The arginine substitution into proline decreased the polarity of the signal peptide for TGF-ß1. The increased hydrophobicity with increased binding energy of the signal peptide for TGF-ß1 to Signal Recognition Particle (SRP) and translocon is shown. This implies decreased protein complex stability in potentially blocking the transport of TGF-ß1 into the endoplasmic reticulum. This transport retention possibly hampers the synthesis and maturation of TGF-ß1 leading to decreased cytokine production.