Uptake of SGLT2i and Outcomes in Patients with Diabetes and Heart Failure: A Population-Based Cohort and a Specialized Clinic Cohort.

BACKGROUND: Sodium-glucose cotransporter-2 (SGLT2) inhibitors are effective in adults with diabetes mellitus (DM) and heart failure (HF) based on randomized clinical trials. We compared SGLT2 inhibitor uptake and outcomes in two cohorts: a population-based cohort of all adults with DM and HF in Alberta, Canada and a specialized heart function clinic (HFC) cohort. METHODS: The population-based cohort was derived from linked provincial healthcare datasets. The specialized clinic cohort was created by chart review of consecutive patients prospectively enrolled in the HFC between February 2018 and August 2022. We examined the association between SGLT2 inhibitor use (modeled as a time-varying covariate) and all-cause mortality or deaths/cardiovascular hospitalizations. RESULTS: Of the 4,885 individuals from the population-based cohort, 64.2% met the eligibility criteria of the trials proving the effectiveness of SGLT2 inhibitors. Utilization of SGLT2 inhibitors increased from 1.2% in 2017 to 26.4% by January 2022. In comparison, of the 530 patients followed in the HFC, SGLT2 inhibitor use increased from 9.8% in 2019 to 49.1 % by March 2022. SGLT2 inhibitor use in the population-based cohort was associated with fewer all-cause mortality (aHR 0.51, 95%CI 0.41-0.63) and deaths/cardiovascular hospitalizations (aHR 0.65, 95%CI 0.54-0.77). However, SGLT2 inhibitor usage rates were far lower in HF patients without DM (3.5% by March 2022 in the HFC cohort). CONCLUSIONS: Despite robust randomized trial evidence of clinical benefit, the uptake of SGLT2 inhibitors in patients with HF and DM remains low, even in the specialized HFC. Clinical care strategies are needed to enhance the use of SGLT2 inhibitors and improve implementation.

Organization and Structures for Detection and Monitoring of CKD Across World Countries and Regions: Observational Data From a Global Survey.

RATIONALE & 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 & 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.

Prescribing patterns and medications costs in patients on maintenance hemodialysis and peritoneal dialysis.

BACKGROUND AND HYPOTHESIS: Polypharmacy is a significant clinical issue for patients on dialysis but has been incompletely studied. We investigated the prevalence and costs of polypharmacy in a population-based cohort of participants treated with hemodialysis (HD) or peritoneal dialysis (PD). METHODS: We studied adults aged ≥ 20 years in Alberta, Canada receiving maintenance HD or PD as of March 31, 2019. We characterized participants as users of 0-29 drug categories of interest and those aged ≥ 65 as users/non-users of potentially inappropriate medications (PIM). We calculated the number of drug categories, daily pill burden, total annual cost, and annual cost per participant, and compared this to an age- and sex-matched cohort from the general Alberta population. RESULTS: Among 2 248 participants (mean age 63 years; 39% female) on HD (n = 1 781) or PD (n = 467), the median number of prescribed drug categories was 6 [interquartile range (IQR) 4, 8]; median daily pill burden was 8.0 (IQR 4.6, 12.6) pills/day, with 5% prescribed ≥ 21.7 pills/day, and 16.5% prescribed ≥ 15 pills/day. Twelve % were prescribed at least one drug that is contraindicated in kidney failure. The median annual per participant cost was ${\$}$3,831, totaling approximately ${\$}$11.6 million annually for all participants. When restricting to the 1 063 participants aged ≥ 65, the median number of PIM categories was 2 (IQR 1, 2), with a median PIM pill burden of 1.2 pills/day (IQR 0.5, 2.4). Compared to PD participants, HD participants had similar daily pill burden, higher use of PIM, and higher annual per participant cost. Pill burden and associated costs for participants on dialysis were more than 3-fold and 10-fold higher, respectively, compared to the matched participants from the general population. CONCLUSION: Participants on dialysis have markedly higher use of prescription medications and associated costs than the general population. Effective methods to de-prescribe in the dialysis population are needed.

Global Kidney Health priorities - Perspectives from the ISN-GKHA.

Kidney diseases have become a global epidemic with significant public health impact. Chronic kidney disease (CKD) is set to become the fifth largest cause of death by 2040, with major impacts on low-resource countries. This review is based on recent report of the International Society of Nephrology Global Kidney Health Atlas (ISN-GKHA) that uncovered gaps in key vehicles of kidney care delivery assessed using World Health Organization building blocks for health systems (financing, services delivery, workforce, access to essential medicines, health information systems, and leadership/governance). High-income countries had more centres for kidney replacement therapies (KRT), higher KRT access, higher allocation of public funds to KRT, larger workforce, more health information systems, and higher government recognition of CKD and KRT as health priorities than low-income nations. Evidence identified from the current ISN-GKHA initiative should serve as template for generating and advancing policies and partnerships to address the global burden of kidney disease. The results provide opportunities for kidney health policymakers, nephrology leaders, and organizations to initiate consultations to identify strategies for improving care delivery and access in equitable, and resource-sensitive manners. Policies to increase use of public funding for kidney care, lower cost of KRT, and increase workforce should be high-priority in low-resource nations, while strategies that expand access to kidney care and maintain current status of care should be prioritized in high-income countries. In all countries, the perspectives of people with CKD should be exhaustively explored to identify core kidney care priorities.

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.

Task shifting roles, interventions and outcomes for kidney and cardiovascular health service delivery among African populations: a scoping review.

BACKGROUND: Human resources for health (HRH) shortages are a major limitation to equitable access to healthcare. African countries have the most severe shortage of HRH in the world despite rising communicable and non-communicable disease (NCD) burden. Task shifting provides an opportunity to fill the gaps in HRH shortage in Africa. The aim of this scoping review is to evaluate task shifting roles, interventions and outcomes for addressing kidney and cardiovascular (CV) health problems in African populations. METHODS: We conducted this scoping review to answer the question: "what are the roles, interventions and outcomes of task shifting strategies for CV and kidney health in Africa?" Eligible studies were selected after searching MEDLINE (Ovid), Embase (Ovid), CINAHL, ISI Web of Science, and Africa journal online (AJOL). We analyzed the data descriptively. RESULTS: Thirty-three studies, conducted in 10 African countries (South Africa, Nigeria, Ghana, Kenya, Cameroon, Democratic Republic of Congo, Ethiopia, Malawi, Rwanda, and Uganda) were eligible for inclusion. There were few randomized controlled trials (n = 6; 18.2%), and tasks were mostly shifted for hypertension (n = 27; 81.8%) than for diabetes (n = 16; 48.5%). More tasks were shifted to nurses (n = 19; 57.6%) than pharmacists (n = 6; 18.2%) or community health workers (n = 5; 15.2%). Across all studies, the most common role played by HRH in task shifting was for treatment and adherence (n = 28; 84.9%) followed by screening and detection (n = 24; 72.7%), education and counselling (n = 24; 72.7%), and triage (n = 13; 39.4%). Improved blood pressure levels were reported in 78.6%, 66.7%, and 80.0% for hypertension-related task shifting roles to nurses, pharmacists, and CHWs, respectively. Improved glycaemic indices were reported as 66.7%, 50.0%, and 66.7% for diabetes-related task shifting roles to nurses, pharmacists, and CHWs, respectively. CONCLUSION: Despite the numerus HRH challenges that are present in Africa for CV and kidney health, this study suggests that task shifting initiatives can improve process of care measures (access and efficiency) as well as identification, awareness and treatment of CV and kidney disease in the region. The impact of task shifting on long-term outcomes of kidney and CV diseases and the sustainability of NCD programs based on task shifting remains to be determined.

The case for increased peritoneal dialysis utilization in low- and lower-middle-income countries.

Peritoneal dialysis (PD) has several advantages compared to haemodialysis (HD), but there is evidence showing underutilization globally, especially in low-income and lower-middle-income countries (LLMICs) where kidney replacement therapies (KRT) are often unavailable, inaccessible, and unaffordable. Only 11% of all dialysis patients worldwide use PD, more than 50% of whom live in China, the United States of America, Mexico, or Thailand. Various barriers to increased PD utilization have been reported worldwide including patient preference, low levels of education, and lower provider reimbursement. However, unique but surmountable barriers are applicable to LLMICs including the excessively high cost of providing PD (related to PD fluids in particular), excessive cost of treatment borne by patients (relative to HD), lack of adequate PD training opportunities for doctors and nurses, low workforce availability for kidney care, and challenges related to some PD outcomes (catheter-related infections, hospitalizations, mortality, etc.). This review discusses some known barriers to PD use in LLMICs and leverages data that show a global trend in reducing rates of PD-related infections, reducing rates of modality switches from HD, and improving patient survival in PD to discuss how PD use can be increased in LLMICs. We therefore, challenge the idea that low PD use in LLMICs is unavoidable due to these barriers and instead present opportunities to improve PD utilization in LLMICs.

Hemodialysis Use and Practice Patterns: An International Survey Study.

RATIONALE & OBJECTIVE: Hemodialysis (HD) is the most common form of kidney replacement therapy. This study aimed to examine the use, availability, accessibility, affordability, and quality of HD care worldwide. STUDY DESIGN: A cross-sectional survey. SETTING & PARTICIPANTS: Stakeholders (clinicians, policy makers, and consumer representatives) in 182 countries were convened by the International Society of Nephrology from July to September 2018. OUTCOMES: Use, availability, accessibility, affordability, and quality of HD care. ANALYTICAL APPROACH: Descriptive statistics. RESULTS: Overall, representatives from 160 (88%) countries participated. Median country-specific use of maintenance HD was 298.4 (IQR, 80.5-599.4) per million population (pmp). Global median HD use among incident patients with kidney failure was 98.0 (IQR, 81.5-140.8) pmp and median number of HD centers was 4.5 (IQR, 1.2-9.9) pmp. Adequate HD services (3-4 hours 3 times weekly) were generally available in 27% of low-income countries. Home HD was generally available in 36% of high-income countries. 32% of countries performed monitoring of patient-reported outcomes; 61%, monitoring of small-solute clearance; 60%, monitoring of bone mineral markers; 51%, monitoring of technique survival; and 60%, monitoring of patient survival. At initiation of maintenance dialysis, only 5% of countries used an arteriovenous access in almost all patients. Vascular access education was suboptimal, funding for vascular access procedures was not uniform, and copayments were greater in countries with lower levels of income. Patients in 23% of the low-income countries had to pay >75% of HD costs compared with patients in only 4% of high-income countries. LIMITATIONS: A cross-sectional survey with possibility of response bias, social desirability bias, and limited data collection preventing in-depth analysis. CONCLUSIONS: In summary, findings reveal substantial variations in global HD use, availability, accessibility, quality, and affordability worldwide, with the lowest use evident in low- and lower-middle-income countries.

Peritoneal Dialysis Use and Practice Patterns: An International Survey Study.

RATIONALE & OBJECTIVE: Approximately 11% of people with kidney failure worldwide are treated with peritoneal dialysis (PD). This study examined PD use and practice patterns across the globe. STUDY DESIGN: A cross-sectional survey. SETTING & PARTICIPANTS: Stakeholders including clinicians, policy makers, and patient representatives in 182 countries convened by the International Society of Nephrology between July and September 2018. OUTCOMES: PD use, availability, accessibility, affordability, delivery, and reporting of quality outcome measures. ANALYTICAL APPROACH: Descriptive statistics. RESULTS: Responses were received from 88% (n=160) of countries and there were 313 participants (257 nephrologists [82%], 22 non-nephrologist physicians [7%], 6 other health professionals [2%], 17 administrators/policy makers/civil servants [5%], and 11 others [4%]). 85% (n=156) of countries responded to questions about PD. Median PD use was 38.1 per million population. PD was not available in 30 of the 156 (19%) countries responding to PD-related questions, particularly in countries in Africa (20/41) and low-income countries (15/22). In 69% of countries, PD was the initial dialysis modality for≤10% of patients with newly diagnosed kidney failure. Patients receiving PD were expected to pay 1% to 25% of treatment costs, and higher (>75%) copayments (out-of-pocket expenses incurred by patients) were more common in South Asia and low-income countries. Average exchange volumes were adequate (defined as 3-4 exchanges per day or the equivalent for automated PD) in 72% of countries. PD quality outcome monitoring and reporting were variable. Most countries did not measure patient-reported PD outcomes. LIMITATIONS: Low responses from policy makers; limited ability to provide more in-depth explanations underpinning outcomes from each country due to lack of granular data; lack of objective data. CONCLUSIONS: Large inter- and intraregional disparities exist in PD availability, accessibility, affordability, delivery, and reporting of quality outcome measures around the world, with the greatest gaps observed in Africa and South Asia.

Availability, coverage, and scope of health information systems for kidney care across world countries and regions.

BACKGROUND: Health 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. METHODS: As 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). RESULTS: Out 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. CONCLUSIONS: These 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.

Building optimal and sustainable kidney care in low resource settings: The role of healthcare systems.

Healthcare systems in low-income and lower-middle income countries (LLMICs) face significant challenges in the provision of health services, for example, kidney care to the population. Although this is linked to several high-level factors such as poor infrastructure, socio-demographic and political factors, healthcare funding has often been cited as the major reason for the wide gap in availability, accessibility and quality of care between LLMICs and rich countries. With the steady rising incidence and prevalence of kidney diseases globally, as well as cost of care, LLMICs are likely to suffer more consequences of these increases than rich countries and may be unable to meet targets of universal health coverage (UHC) for kidney diseases. As health systems in LLMICs continue to adapt in finding ways to provide access to affordable kidney care, various empirical and evidence-based strategies can be applied to assist them. This review uses a framework for healthcare strengthening developed by the World Health Organization (WHO) to assess various challenges that health systems in LLMICs confront in providing optimal kidney care to their population. We also suggest ways to overcome these barriers and strengthen health systems to improve kidney care in LLMICs.

Diagnostic performance of glomerular PLA2R and THSD7A antibodies in biopsy confirmed primary membranous nephropathy in South Africans.

BACKGROUND: Serum and tissue-based tests using phospholipase A2 receptor 1 (PLA2R) and thrombospondin type-1 domain containing 7A (THSD7A) are established immune biomarkers for the diagnosis of primary membranous nephropathy (PMN). This study assessed the diagnostic performance of these biomarkers in the diagnosis of PMN in South Africans. METHODS: This was a cross-sectional analysis from a single centre in Cape Town, South Africa. Relevant biodata was collected from all patients. Histology, including slides for PLA2R and THSD7A were processed and assessed by typical microscopic and immunohistochemical features. Biopsy tissues of patients with membranous lupus nephritis (LN-V) and diabetic nephropathy (DN) were used as controls. The diagnostic accuracy for diagnosis of PMN using positive PLA2R and THSD7A were evaluated. RESULTS: Of the 88 patients included, 41 had PMN with a mean age of 44.5 ± 17.5 years and 61.0% were female. Histologically, PLA2R and THSD7A were only positive in the PMN group (51.2% and 4.9%, respectively) but negative in both control groups. The sensitivity of PLA2R and THSD7A for identifying PMN was 51.2% and 4.9%, respectively. The sensitivity of both tests together was 53.7% while the specificity and positive predictive values (PPV) for any of the tests (alone or in combination) was 100%. There was no difference in the sensitivity and specificity when using PLA2R alone compared to combining the two tests (p=0.32). CONCLUSION: Glomerular staining of PLA2R and THSD7A could have potential diagnostic values in South Africans. This has implications on how immunotherapies can be initiated and used in these settings.

Online clinical pathway for chronic kidney disease management in primary care: a retrospective cohort study.

BACKGROUND: Clinical pathways aim to improve patient care. We sought to determine whether an online chronic kidney disease (CKD) clinical pathway was associated with improvements in CKD management. METHODS: We conducted a retrospective pre/post population-based cohort study using linked health data from Alberta, Canada. We included adults 18 years or older with mean estimated glomerular filtration rate (eGFR) < 60 ml/min/1.73m2. The primary outcome was measurement of an outpatient urine albumin creatinine ratio (ACR) in a 28-day period, among people without a test in the prior year. Secondary outcomes included use of guideline-recommended drug therapies (angiotensin-converting enzyme inhibitors, angiotensin receptor blockers and statins). RESULTS: The study period spanned October 2010 to March 2017. There were 84 independent 28-day periods (53 pre, 31 post pathway implementation) including 345,058 adults. The population was predominantly female (56%) with median age 77 years; most had category 3A CKD (67%) and hypertension (82%). In adjusted segmented regression models, the increase in the rate of change of ACR testing was greatest in Calgary zone (adjusted OR 1.19 per year, 95% CI 1.16-1.21), where dissemination of the pathway was strongest; this increase was more pronounced in those without diabetes (adjusted OR 1.25 per year, 95% CI 1.21-1.29). Small improvements in guideline-concordant medication use were also observed. CONCLUSIONS: Following implementation of an online CKD clinical pathway, improvements in ACR testing were evident in regions where the pathway was most actively used, particularly among individuals without diabetes.

Strategic plan for integrated care of patients with kidney failure.

There is a huge gap between the number of patients worldwide requiring versus those actually receiving safe, sustainable, and equitable care for kidney failure. To address this, the International Society of Nephrology coordinated the development of a Strategic Plan for Integrated Care of Patients with Kidney Failure. Implementation of the plan will require engagement of the whole kidney community over the next 5-10 years.

Fluid management in chronic kidney disease: what is too much, what is the distribution, and how to manage fluid overload in patients with chronic kidney disease?

PURPOSE OF REVIEW: Assessment of fluid status to reach normovolemia in patients with chronic kidney disease (CKD) continues to be a tough task. Besides clinical observation, technological methods have been introduced, yet, the best approach is still uncertain. The present review looks at fluid overload in CKD from three perspectives: the critical fluid threshold leading to adverse cardiovascular outcomes, fluid distribution and its clinical correlates, and direct effect of fluid overload on vascular function related to disturbance of the sodium-skin axis and endothelial glycocalyx dysfunction. RECENT FINDINGS: To determine fluid status, both the absolute and relative fluid overload is used as parameter in clinical practice. In addition, the definition of fluid overload is ambivalent and its relation to symptom burden has not been studied well. Studies on the impact of distribution of fluid are scarce and the limited evidence suggests differences based on the cause of CKD. So far, no standardized technologies are available to adequately determine fluid distribution. After discovering the 'third compartment' of total body sodium in skin and muscle tissue and its potential direct effect on vascular function, other biomarkers such as VEGF-C are promising. SUMMARY: We propose a multimodal clinical approach for volume management in CKD. Because there are currently no studies are available demonstrating that correction of fluid overload in CKD will lead to better outcome, these are strongly needed.

Association of Genetic Polymorphisms of TGF-ß1, HMOX1, and APOL1 With CKD in Nigerian Patients With and Without HIV.

RATIONALE & OBJECTIVE: Recent studies in the human immunodeficiency virus (HIV)-infected population have suggested that there are genetic predispositions to the development of chronic kidney disease (CKD) in this context. We investigated the association of genetic polymorphisms of the genes encoding apolipoprotein L1 (APOL1), transforming growth factor ß1 (TGF-ß1; a profibrotic cytokine), and heme oxygenase 1 (HMOX1) with prevalent CKD among adults with and without HIV infection. STUDY DESIGN: Case-control study. SETTING & PARTICIPANTS: West African adults including 217 HIV-infected patients with CKD (HIV+/CKD+ group), 595 HIV-infected patients without CKD (HIV+/CKD- group), 269 with CKD and no HIV infection (HIV-/CKD+ group), and 114 with neither CKD nor HIV (HIV-/CKD- group). EXPOSURE: The genetic polymorphisms with reference single-nucleotide polymorphism (rs) identification numbers rs1800469 (TGF-ß1), rs1800470 (TGF-ß1), rs121918282 (TGF-ß1); rs60910145 (APOL1 G1 risk allele), rs73885319 (APOL1 G1 risk allele), rs71785313 (APOL1 G2 risk allele), and rs743811 (HMOX1); HIV. OUTCOME: CKD. ANALYTICAL APPROACH: Single-nucleotide polymorphism (SNP) genotyping of rs1800469 (TGF-ß1), rs1800470 (TGF-ß1), rs121918282 (TGF-ß1); rs60910145 (APOL1), rs73885319 (APOL1), rs71785313 (APOL1), and rs743811 (HMOX1) was performed. Hardy-Weinberg equilibrium was evaluated for all SNPs, and minor allele frequencies were reported. A case-control analysis was performed, and multivariable logistic regression was used to control for potential confounders. RESULTS: Minor allele frequencies for TGF-ß1 (rs1800469, rs1800470, and rs1800471), APOL1 (rs60910145, rs73885319, and rs71785313), and HMOX1 (rs743811) were 0.25, 0.46, 0.46, 0.44, 0.45, 0.17, and 0.14, respectively. Among HIV-positive individuals, only TGF-ß1 rs1800470 (GG vs AA), APOL1 (in the recessive model), and hypertension were associated with prevalent CKD (adjusted ORs of 0.44 [95% CI, 0.20-0.97], 2.54 [95% CI, 1.44-4.51], and 2.17 [95% CI, 1.35-3.48], respectively). No SNP polymorphisms were associated with prevalent CKD among HIV-negative individuals. LIMITATIONS: The lack of histopathology data for proper categorization of the type of HIV-related nephropathy. CONCLUSIONS: APOL1 polymorphisms were highly prevalent in this population and among adult patients infected with HIV and were associated with increased CKD risk. The TGF-ß1 (rs1800470) polymorphism was associated with reduced risk, and HMOX1 polymorphisms were unassociated with CKD.

Availability and Affordability of Kidney Health Laboratory Tests around the Globe.

BACKGROUND: Kidney disease is a major global public health problem, and laboratory testing of kidney health measures is essential for diagnosis and monitoring. The availability and affordability of kidney health laboratory tests across countries has not been systematically described. METHODS: The International Society of Nephrology (ISN), in partnership with leaders of a Kidney Disease: Improving Global Outcomes (KDIGO) Controversies Conference, surveyed a representative subset of ISN-Global Kidney Health Atlas (ISN-GKHA) respondents from April to June 2020. We assessed the association between country gross national income (GNI) per capita and laboratory testing availability and affordability. RESULTS: Of 33 regional expert nephrologists invited, 24 (73%) responded, representing all 10 ISN regions around the world. Availability of kidney health laboratory tests was as follows: serum Cr (100%), serum cystatin C (67%), urine albumin (96%), urine Cr (100%), and dipstick urinalysis (100%). Median (IQR) reimbursement values in international dollars were as follows: serum Cr Int$ 6.61 (3.42-8.84), serum cystatin C Int$ 31.51 (17.36-46.25), urine albumin Int$ 10.22 (5.90-15.42), urine Cr Int$ 7.50 (1.66-8.84), and dipstick urinalysis Int$ 6.26 (2.56-8.40). Reimbursement values did not differ significantly by World Bank income group or by GNI per capita. CONCLUSION: There was widespread availability of kidney health laboratory tests and substantial variation in reimbursement values. To achieve meaningful progress across nations in mitigating the growth of kidney disease, access to affordable diagnostic technology is essential. Our results are highly relevant to policymakers and researchers as countries increasingly consider national strategies for kidney disease detection and management.

Extracellular fluid volume expansion, arterial stiffness and uncontrolled hypertension in patients with chronic kidney disease.

BACKGROUND: Hypertension is prevalent in patients with chronic kidney disease (CKD) and is related to extracellular fluid volume (ECFV) expansion. Arterial stiffening is another implication of CKD that can be caused by ECFV expansion. In this study, we hypothesized that CKD patients with uncontrolled hypertension are more likely to be fluid volume expanded than normotensive patients, which in turn is associated with increased arterial stiffness. METHODS: Adult hypertensive patients with mild-severe CKD (n = 82) were recruited. ECFV was assessed using multifrequency bioimpedance and arterial stiffness by applanation tonometry and oscillometry. RESULTS: Patients with uncontrolled hypertension had fluid volume expansion compared with controls (1.0 ± 1.5 versus 0.0 ± 1.6 L, P < 0.001), and had a higher augmentation index (AIx) and pulse wave velocity. Fluid volume expansion was more prevalent in patients with uncontrolled hypertension (58%) than patients who were at target (27%). Fluid volume expansion was correlated with age, AIx and systolic blood pressure. In a binary logistic regression analysis, AIx, age and fluid volume status were independent predictors of uncontrolled hypertension in both univariate and multivariate models. DISCUSSION: In summary, uncontrolled hypertension among hypertensive CKD patients is associated with ECFV expansion. Our data suggest a relationship between ECFV expansion, increased arterial stiffness and uncontrolled hypertension.

Kidney care in low- and middle-income countries.

Optimal kidney care requires a trained nephrology workforce, essential healthcare services, and medications. This study aimed to identify the access to these resources on a global scale using data from the multinational survey conducted by the International Society of Nephrology (ISN) (Global Kidney Health Atlas (GKHA) project), with emphasis on developing nations. For data analysis, the 125 participating countries were sorted into the 4 World Bank income groups: low income (LIC), lower-middle income (LMIC), upper-middle income (UMIC), and high income (HIC). A severe shortage of nephrologists was observed in LIC and LMIC with < 5 nephrologists per million population. Many LIC were unable to access estimated glomerular filtration rate (eGFR) and albuminuria (proteinuria) tests in primary-care levels. Acute and chronic hemodialysis was available in most countries, although acute and chronic peritoneal dialysis access was severely limited in LIC (24% and 35%, respectively). Most countries had kidney transplantation access, except for LIC (12%). HIC and UMIC funded their renal replacement therapy (RRT) and renal medications primarily through public means, whereas LMIC and LIC required private and out-of-pocket contributions. In conclusion, this study found a huge gap in the availability and access to trained nephrology workforce, tools for diagnosis and management of CKD, RRT, and funding of RRT and essential medications in LIC and LMIC.