Global variability of vascular and peritoneal access for chronic dialysis

AIM: Vascular and peritoneal access are essential elements for sustainability of chronic dialysis programs. Data on availability, patterns of use, funding models, and workforce for vascular and peritoneal accesses for dialysis at a global scale is limited. METHODS: An electronic survey of national leaders of nephrology societies, consumer representative organizations, and policymakers was conducted from July to September 2018. Questions focused on types of accesses used to initiate dialysis, funding for services, and availability of providers for access creation. RESULTS: Data from 167 countries were available. In 31 countries (25% of surveyed countries), >75% of patients initiated haemodialysis (HD) with a temporary catheter. Seven countries (5% of surveyed countries) had >75% of patients initiating HD with arteriovenous fistulas or grafts. Seven countries (5% of surveyed countries) had >75% of their patients starting HD with tunnelled dialysis catheters. 57% of low-income countries (LICs) had >75% of their patients initiating HD with a temporary catheter compared to 5% of high-income countries (HICs). Shortages of surgeons to create vascular access were reported in 91% of LIC compared to 46% in HIC. Approximately 95% of participating countries in the LIC category reported shortages of surgeons for peritoneal dialysis (PD) access compared to 26% in HIC. Public funding was available for central venous catheters, fistula/graft creation, and PD catheter surgery in 57%, 54% and 54% of countries, respectively. CONCLUSION: There is a substantial variation in the availability, funding, workforce, and utilization of vascular and peritoneal access for dialysis across countries regions, with major gaps in low-income countries

Global variations in funding and use of hemodialysis accesses: an international report using the ISN Global Kidney Health Atlas

Background: There is a lack of contemporary data describing global variations in vascular access for hemodialysis (HD). We used the third iteration of the International Society of Nephrology Global Kidney Health Atlas (ISN-GKHA) to highlight differences in funding and availability of hemodialysis accesses used for initiating HD across world regions. Methods: Survey questions were directed at understanding the funding modules for obtaining vascular access and types of accesses used to initiate dialysis. An electronic survey was sent to national and regional key stakeholders affiliated with the ISN between June and September 2022. Countries that participated in the survey were categorized based on World Bank Income Classification (low-, lower-middle, upper-middle, and high-income) and by their regional affiliation with the ISN. Results: Data on types of vascular access were available from 160 countries. Respondents from 35 countries (22% of surveyed countries) reported that > 50% of patients started HD with an arteriovenous fistula or graft (AVF or AVG). These rates were higher in Western Europe (n = 14; 64%), North & East Asia (n = 4; 67%), and among high-income countries (n = 24; 38%). The rates of > 50% of patients starting HD with a tunneled dialysis catheter were highest in North America & Caribbean region (n = 7; 58%) and lowest in South Asia and Newly Independent States and Russia (n = 0 in both regions). Respondents from 50% (n = 9) of low-income countries reported that > 75% of patients started HD using a temporary catheter, with the highest rates in Africa (n = 30; 75%) and Latin America (n = 14; 67%). Funding for the creation of vascular access was often through public funding and free at the point of delivery in high-income countries (n = 42; 67% for AVF/AVG, n = 44; 70% for central venous catheters). In low-income countries, private and out of pocket funding was reported as being more common (n = 8; 40% for AVF/AVG, n = 5; 25% for central venous catheters). Conclusions: High income countries exhibit variation in the use of AVF/AVG and tunneled catheters. In low-income countries, there is a higher use of temporary dialysis catheters and private funding models for access creation

Intractable ascites in a female receiving hemodialysis

We report a case of a 60-year-old female who presented with intractable ascites 2 months after switching from peritoneal dialysis (PD) to hemodialysis (HD) due to an episode of refractory culture-negative peritonitis (CNP). Abdominal paracentesis yielded inflammatory ascites, which later grew Cladosporium cladosporioides, establishing the diagnosis of fungal peritonitis. She was successfully treated with a 4-week course of oral voriconazole. Cladosporium spp. are common fungi in the environment but rarely cause PD-associated peritonitis and can be challenging to diagnose with conventional microbiologic evaluation. In summary, PD-associated peritonitis can worsen after a patient switches to HD. Therefore, it is essential to maintain a high level of suspicion for such complications related to their previous dialysis modality to arrive at an accurate diagnosis

Uremia-Induced Gut Barrier Defect in 5/6 Nephrectomized Mice Is Worsened by Candida Administration through a Synergy of Uremic Toxin, Lipopolysaccharide, and (1➔3)-β-D-Glucan, but Is Attenuated by Lacticaseibacillus rhamnosus L34

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

The effect of polymyxin B hemoperfusion on modulation of human leukocyte antigen DR in severe sepsis patients

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

Progress of nations in the organization of, and structures for kidney care delivery between 2019 and 2023:Findings from a multinational survey of 148 countries

OBJECTIVETo assess changes in key measures of kidney care using International Society of Nephrology Global Kidney Health Atlas (ISN-GKHA) data reported in 2019 and 2023.DESIGN: International cross-sectional surveySETTINGInternational Society of Nephrology Global Kidney Health Atlas (ISN-GKHA) surveys of 2019 and 2023 that included participants from countries in Africa (n=36), Eastern and Central Europe (n=16), Latin America (n=18), the Middle East (n=11), NIS and Russia (n=10), North America and the Caribbean (n=8), North and East Asia (n=6), OSEA (n=15), South Asia (n=7), and Western Europe (n=21).PARTICIPANTSCountries that participated in both surveys (2019 and 2023)MAIN OUTCOME MEASURESComparison of 2019 and 2023 ISN-GKHA data on availability of kidney replacement therapy (KRT) services, access, health financing, workforce, registries, and policies for kidney care. Data for countries that participated in both surveys (2019 and 2023) were included in our analysis. Country data were aggregated by ISN regions and World Bank income levels. Proportionate changes in the status of these measures across both periods were reported.RESULTSData for 148 countries that participated in both surveys were available for analysis. The proportions of countries that provided public funding (free at point of delivery) increased from 27% in 2019 to 28% in 2023 for hemodialysis (HD), 23% to 28% for peritoneal dialysis (PD), and 31% to 36% for kidney transplantation (KT) services. Hemodialysis, PD, and KT centers increased from 4.4 per million population [pmp] to 4.8 pmp (P&lt;0.001), 1.4 pmp to 1.6 pmp, and 0.43 pmp to 0.46 pmp, respectively. Overall, access to HD and PD improved, however, access to KT decreased from 30 pmp to 29 pmp. The global median prevalence of nephrologists increased from 9.5 pmp to 12.4 pmp (P&lt;0.001). Changes across regions and country income levels in the availability of kidney registries and in national policies and strategies for kidney care were variable. The reporting of specific barriers to optimal kidney care by countries increased from 55% to 59%, 58% to 68% (P=0.043), and 46% to 52% for geographical factors, availability of nephrologists, and political factors, respectively.CONCLUSIONS:Important changes in key areas of kidney care delivery were noted across both periods globally. These changes impacted largely the availability of, and access to KT services. There is an important need for countries and regions to enact enabling strategies for preserving access to kidney care services, particularly kidney transplantation. <br/

<i>Candida</i> Administration in 5/6 Nephrectomized Mice Enhanced Fibrosis in Internal Organs: An Impact of Lipopolysaccharide and (1→3)-β-D-Glucan from Leaky Gut

Uremic toxins and gut dysbiosis in advanced chronic kidney disease (CKD) can induce gut leakage, causing the translocation of gut microbial molecules into the systemic circulation. Lipopolysaccharide (LPS) and (1→3)-β-D-glucan (BG) are the major gut microbial molecules of Gram-negative bacteria and fungi, respectively, and can induce inflammation in several organs. Here, the fibrosis in the kidney, liver, and heart was investigated in oral C. albicans-administered 5/6 nephrectomized (Candida-5/6 Nx) mice. At 20 weeks post 5/6 Nx, Candida-5/6 Nx mice demonstrated increased 24 h proteinuria, liver enzymes, and serum cytokines (TNF-α, IL-6, and IL-10), but not weight loss, systolic blood pressure, hematocrit, serum creatinine, or gut-derived uremic toxins (TMAO and indoxyl sulfate), compared to in 5/6 Nx alone. The gut leakage in Candida-5/6 Nx was more severe, as indicated by FITC-dextran assay, endotoxemia, and serum BG. The areas of fibrosis from histopathology, along with the upregulated gene expression of Toll-like receptor 4 (TLR-4) and Dectin-1, the receptors for LPS and BG, respectively, were higher in the kidney, liver, and heart. In vitro, LPS combined with BG increased the supernatant IL-6 and TNF-α, upregulated the genes of pro-inflammation and pro-fibrotic processes, Dectin-1, and TLR-4 in renal tubular (HK-2) cells and hepatocytes (HepG2), when compared with LPS or BG alone. This supported the pro-inflammation-induced fibrosis and the possible LPS–BG additive effects on kidney and liver fibrosis. In conclusion, uremia-induced leaky gut causes the translocation of gut LPS and BG into circulation, which activates the pro-inflammatory and pro-fibrotic pathways, causing internal organ fibrosis. Our results support the crosstalk among several organs in CKD through a leaky gut

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

IntroductionChronic 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.MethodsThe 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.ResultA 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.ConclusionCU 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

Organization and structures for detection and monitoring of CKD across world countries and regions:Observational data from a global survey

Rationale &amp; Objective: Established therapeutic interventions effectively mitigate the risk and progression of chronic kidney disease (CKD). Countries and regions have a compelling need for organizational structures that enable early identification of people with CKD who can benefit from these proven interventions. We aimed to report the current global status of CKD detection programs. Study Design: A multinational cross-sectional survey. Setting &amp; Participants:Stakeholders, including nephrologist leaders, policymakers, and patient advocates from 167 countries, participating in the International Society of Nephrology (ISN) survey from June to September 2022.Outcomes:Structures for the detection and monitoring of CKD, including CKD surveillance systems in the form of registries, community-based detection programs, case-finding practices, and availability of measurement tools for risk identification.Analytical Approach:Descriptive statistics.Results: Of all participating countries, 19% (n=31) reported CKD registries and 25% (n=40) reported implementing CKD detection programs as part of their national policies. There were variations in CKD detection program, with 50% (n=20) using a reactive approach (managing cases as identified) and 50% (n=20) actively pursuing case-finding in at-risk populations. Routine case-finding for CKD in high-risk populations was widespread, particularly for diabetes (n=152; 91%) and hypertension (n=148; 89%). Access to diagnostic tools, estimated glomerular filtration rate (eGFR) and urine albumin-creatinine ratio (UACR), was limited, especially in low-income (LICs) and lower-middle-income (LMICs) countries, at primary (eGFR: LICs 22%, LMICs 39%, UACR: LICs 28%, LMICs 39%) and secondary/tertiary healthcare levels (eGFR: LICs 39%, LMICs 73%, UACR: LICs 44%, LMICs 70%), potentially hindering CKD detection. Limitations:A lack of detailed data prevented an in-depth analysis.Conclusion:This comprehensive survey highlights a global heterogeneity in the organization and structures (surveillance systems, detection programs and tools) for early identification of CKD. Ongoing efforts should be geared toward bridging such disparities to optimally prevent the onset and progression of CKD and its complications.<br/