Phase 2 Trial of Cemdisiran in Adult Patients with IgA Nephropathy: A Randomized Controlled Trial.

BACKGROUND: IgA nephropathy is the most common primary GN. Clinical features of IgA nephropathy include proteinuria, which is the strongest known surrogate of progression to kidney failure. Complement pathway activation is a critical driver of inflammation and tissue injury in IgA nephropathy. Cemdisiran is an investigational RNA interference therapeutic that suppresses hepatic production of complement component 5 (C5), thereby potentially reducing proteinuria in IgA nephropathy. We evaluated the efficacy and safety of cemdisiran in adult patients with IgA nephropathy at high risk of kidney disease progression. METHODS: In this phase 2, 36-week, double-blind study, adult patients with IgA nephropathy and urine protein ≥1 g/24 hours were randomized (2:1) to subcutaneous cemdisiran 600 mg or placebo every 4 weeks in combination with the standard of care. The primary end point was percentage change from baseline at week 32 in urine protein-to-creatinine ratio (UPCR) measured by 24-hour urine collection. Additional end points included change from baseline in UPCR measured by spot urine, serum C5 level, and safety assessments. RESULTS: Thirty-one patients were randomized (cemdisiran, N =22; placebo, N =9). Cemdisiran-treated patients had a placebo-adjusted geometric mean change in 24-hour UPCR of -37.4% (cemdisiran-adjusted geometric mean ratio to baseline [SEM], 0.69 [0.10]) at week 32. Spot UPCR was consistent with 24-hour UPCR placebo-adjusted change of -45.8% (cemdisiran-adjusted geometric mean ratio to baseline [SEM], 0.73 [0.11]). Mean (SD) change in serum C5 level from baseline at week 32 was -98.7% (1.2) with cemdisiran and 25.2% (57.7) with placebo. Over 36 weeks, most adverse events were mild or moderate and transient; the most common adverse event after cemdisiran treatment was injection-site reaction (41%). CONCLUSIONS: These findings indicate that treatment with cemdisiran resulted in a reduction of proteinuria at week 32 and was well tolerated.

Post hoc analysis of the SONAR trial indicates that the endothelin receptor antagonist atrasentan is associated with less pain in patients with type 2 diabetes and chronic kidney disease.

Pain is prevalent among patients with diabetes and chronic kidney disease (CKD). The management of chronic pain in these patients is limited by nephrotoxicity of commonly used drugs including non-steroidal anti-inflammatory drugs (NSAIDs) and opioids. Since previous studies implicated endothelin-1 in pain nociception, our post hoc analysis of the SONAR trial assessed the association between the endothelin receptor antagonist atrasentan and pain and prescription of analgesics. SONAR was a randomized, double-blind, placebo-controlled clinical trial that recruited participants with type 2 diabetes and CKD (estimated glomerular filtration rate 25-75 ml/min/1.73 m2; urinary albumin-to-creatinine ratio 300-5000 mg/g). Participants were randomized to receive atrasentan or placebo (1834 each arm). The main outcome was pain-related adverse events (AEs) reported by investigators. We applied Cox regression to assess the effect of atrasentan compared to placebo on the risk of the first reported pain-related AE and, secondly, first prescription of analgesics. We used the Anderson-Gill method to assess effects on all (first and subsequent) pain-related AEs. During 2.2-year median follow-up, 1183 pain-related AEs occurred. Rates for the first pain-related event were 138.2 and 170.2 per 1000 person-years in the atrasentan and placebo group respectively (hazard ratio 0.82 [95% confidence interval 0.72-0.93]). Atrasentan also reduced the rate of all (first and subsequent) pain-related AEs (rate ratio 0.80 [0.70-0.91]). These findings were similar after accounting for competing risk of death (sub-hazard ratio 0.81 [0.71-0.92]). Patients treated with atrasentan initiated fewer analgesics including NSAIDs and opioids compared to placebo during follow-up (hazard ratio = 0.72 [0.60-0.88]). Thus, atrasentan was associated with reduced pain-related events and pain-related use of analgesics in carefully selected patients with type 2 diabetes and CKD.

Insulin resistance, kidney outcomes and effects of the endothelin receptor antagonist atrasentan in patients with type 2 diabetes and chronic kidney disease.

BACKGROUND: Insulin resistance (IR) is a pathophysiologic hallmark of type 2 diabetes and associated with the presence of chronic kidney disease (CKD). Experimental studies suggest that endothelin-1 increases IR. We assessed the association between IR and cardio-renal outcomes and the effect of the selective endothelin receptor antagonist atrasentan on IR in patients with type 2 diabetes and CKD. METHODS: We used data from the RADAR and SONAR trials that recruited participants with type 2 diabetes and CKD [eGFR 25-75 mL/min/1.73 m², urine albumin-to-creatinine ratio of 300-5000 mg/g]. IR was calculated using the homeostatic model assessment (HOMA-IR). The association between HOMA-IR and the pre-specified cardio-renal outcomes was assessed using multivariable Cox proportional hazards regression, and effects of atrasentan on HOMA-IR by a linear mixed effect model. RESULTS: In the SONAR trial, each log-unit increase in HOMA-IR was associated with an increased risk of the composite cardio-renal outcome [hazard ratio 1.32 (95%CI 1.09,1.60; p = 0.004)], kidney outcome [hazard ratio 1.30 (95%CI 1.00,1.68; p-value = 0.048)], and the kidney or all-cause mortality outcome [hazard ratio 1.25 (95%CI 1.01,1.55; p-value = 0.037)]. After 12 weeks treatment in the RADAR trial (N = 123), atrasentan 0.75 mg/day and 1.25 mg/day compared to placebo reduced HOMA-IR by 19.1 (95%CI -17.4, 44.3) and 26.7% (95%CI -6.4, 49.5), respectively. In the SONAR trial (N = 1914), atrasentan 0.75 mg/day compared to placebo reduced HOMA-IR by 9.6% (95%CI 0.6, 17.9). CONCLUSIONS: More severe IR is associated with increased risk of cardio-renal outcomes. The endothelin receptor antagonist atrasentan reduced IR. TRIAL REGISTRATION: RADAR trial (Reducing Residual Albuminuria in Subjects With Diabetes and Nephropathy With AtRasentan): NCT01356849. SONAR trial (The Study Of Diabetic Nephropathy With AtRasentan) NCT01858532.

Practical considerations for the use of SGLT-2 inhibitors in the Asia-Pacific countries-An expert consensus statement.

Recent clinical studies have demonstrated the effectiveness of SGLT-2 inhibitors in reducing the risks of cardiovascular and renal events in both patients with and without type 2 diabetes mellitus. Consequently, many international guidelines have begun advocating for the use of SGLT-2 inhibitors for the purpose of organ protection rather than as simply a glucose-lowering agent. However, despite the consistent clinical benefits and available strong guideline recommendations, the utilization of SGLT-2 inhibitors have been unexpectedly low in many countries, a trend which is much more noticeable in low resource settings. Unfamiliarity with the recent focus in their organ protective role and clinical indications; concerns with potential adverse effects of SGLT-2 inhibitors, including acute kidney injury, genitourinary infections, euglycemic ketoacidosis; and their safety profile in elderly populations have been identified as deterring factors to their more widespread use. This review serves as a practical guide to clinicians managing patients who could benefit from SGLT-2 inhibitors treatment and instill greater confidence in the initiation of these drugs, with the aim of optimizing their utilization rates in high-risk populations.

Home dialysis: conclusions from a Kidney Disease: Improving Global Outcomes (KDIGO) Controversies Conference.

Home dialysis modalities (home hemodialysis [HD] and peritoneal dialysis [PD]) are associated with greater patient autonomy and treatment satisfaction compared with in-center modalities, yet the level of home-dialysis use worldwide is low. Reasons for limited utilization are context-dependent, informed by local resources, dialysis costs, access to healthcare, health system policies, provider bias or preferences, cultural beliefs, individual lifestyle concerns, potential care-partner time, and financial burdens. In May 2021, KDIGO (Kidney Disease: Improving Global Outcomes) convened a controversies conference on home dialysis, focusing on how modality choice and distribution are determined and strategies to expand home-dialysis use. Participants recognized that expanding use of home dialysis within a given health system requires alignment of policy, fiscal resources, organizational structure, provider incentives, and accountability. Clinical outcomes across all dialysis modalities are largely similar, but for specific clinical measures, one modality may have advantages over another. Therefore, choice among available modalities is preference-sensitive, with consideration of quality of life, life goals, clinical characteristics, family or care-partner support, and living environment. Ideally, individuals, their care-partners, and their healthcare teams will employ shared decision-making in assessing initial and subsequent kidney failure treatment options. To meet this goal, iterative, high-quality education and support for healthcare professionals, patients, and care-partners are priorities. Everyone who faces dialysis should have access to home therapy. Facilitating universal access to home dialysis and expanding utilization requires alignment of policy considerations and resources at the dialysis-center level, with clear leadership from informed and motivated clinical teams.

Kidney health for all: preparedness for the unexpected in supporting the vulnerable.

As the rate of natural disasters and other devastating events caused by human activities increases, the burden on the health and well-being of those affected by kidney disease has been immeasurable. Health system preparedness, which involves creating a resilient system that is able to deal with the health needs of the entire community during times of unexpected disruptions to usual care, has become globally important. In the wake of the COVID-19 pandemic, there is a heightened awareness of the amplification of negative effects on the renal community. Paradoxically, the complex medical needs of those who have kidney diseases are not met by systems handling crises, often compounded by an acute increase in burden via new patients as a result of the crisis itself. Disruptions in kidney care as a result of unexpected events are becoming more prevalent and likely to increase in the years to come. It is therefore only appropriate that the theme for this year's World Kidney Day will focus on Kidney Health for All: preparedness for the unexpected in supporting the vulnerable.

Diabetes Management in Chronic Kidney Disease: Synopsis of the KDIGO 2022 Clinical Practice Guideline Update.

DESCRIPTION: The KDIGO 2022 Clinical Practice Guideline for Diabetes Management in Chronic Kidney Disease is an update of the 2020 guideline from Kidney Disease: Improving Global Outcomes (KDIGO). METHODS: The KDIGO Work Group updated the guideline, which included reviewing and grading new evidence that was identified and summarized. As in the previous guideline, the Work Group used the GRADE (Grading of Recommendations Assessment, Development and Evaluation) approach to appraise evidence and rate the strength of recommendations and expert judgment to develop consensus practice points. New evidence led to updating of recommendations in the chapters Comprehensive Care in Patients With Diabetes and CKD (Chapter 1) and Glucose-Lowering Therapies in Patients With T2D and CKD (Chapter 4). New evidence did not change recommendations in the chapters Glycemic Monitoring and Targets in Patients With Diabetes and CKD (Chapter 2), Lifestyle Interventions in Patients With Diabetes and CKD (Chapter 3), and Approaches to Management of Patients With Diabetes and CKD (Chapter 5). RECOMMENDATIONS: The updated guideline includes 13 recommendations and 52 practice points for clinicians caring for patients with diabetes and chronic kidney disease (CKD). A focus on preserving kidney function and maintaining well-being is recommended using a layered approach to care, starting with a foundation of lifestyle interventions, self-management, and first-line pharmacotherapy (such as sodium-glucose cotransporter-2 inhibitors) demonstrated to improve clinical outcomes. To this are added additional drugs with heart and kidney protection, such as glucagon-like peptide-1 receptor agonists and nonsteroidal mineralocorticoid receptor antagonists, and interventions to control risk factors for CKD progression and cardiovascular events, such as blood pressure, glycemia, and lipids.

Development and deployment of a nationwide predictive model for chronic kidney disease progression in diabetic patients.

Aim: Chronic kidney disease (CKD) is a major complication of diabetes and a significant disease burden on the healthcare system. The aim of this work was to apply a predictive model to identify high-risk patients in the early stages of CKD as a means to provide early intervention to avert or delay kidney function deterioration. Materials and methods: Using the data from the National Diabetes Database in Singapore, we applied a machine-learning algorithm to develop a predictive model for CKD progression in diabetic patients and to deploy the model nationwide. Results: Our model was rigorously validated. It outperformed existing models and clinician predictions. The area under the receiver operating characteristic curve (AUC) of our model is 0.88, with the 95% confidence interval being 0.87 to 0.89. In recognition of its higher and consistent accuracy and clinical usefulness, our CKD model became the first clinical model deployed nationwide in Singapore and has been incorporated into a national program to engage patients in long-term care plans in battling chronic diseases. The risk score generated by the model stratifies patients into three risk levels, which are embedded into the Diabetes Patient Dashboard for clinicians and care managers who can then allocate healthcare resources accordingly. Conclusion: This project provided a successful example of how an artificial intelligence (AI)-based model can be adopted to support clinical decision-making nationwide.

The role of BAFF and APRIL in IgA nephropathy: pathogenic mechanisms and targeted therapies.

Immunoglobulin A nephropathy (IgAN), characterized by mesangial deposition of galactose-deficient-IgA1 (Gd-IgA1), is the most common biopsy-proven primary glomerulonephritis worldwide. Recently, an improved understanding of its underlying pathogenesis and the substantial risk of progression to kidney failure has emerged. The "four-hit hypothesis" of IgAN pathogenesis outlines a process that begins with elevated circulating levels of Gd-IgA1 that trigger autoantibody production. This results in the formation and deposition of immune complexes in the mesangium, leading to inflammation and kidney injury. Key mediators of the production of Gd-IgA1 and its corresponding autoantibodies are B-cell activating factor (BAFF), and A proliferation-inducing ligand (APRIL), each playing essential roles in the survival and maintenance of B cells and humoral immunity. Elevated serum levels of both BAFF and APRIL are observed in patients with IgAN and correlate with disease severity. This review explores the complex pathogenesis of IgAN, highlighting the pivotal roles of BAFF and APRIL in the interplay between mucosal hyper-responsiveness, B-cell activation, and the consequent overproduction of Gd-IgA1 and its autoantibodies that are key features in this disease. Finally, the potential therapeutic benefits of inhibiting BAFF and APRIL in IgAN, and a summary of recent clinical trial data, will be discussed.

Availability and prioritisation of COVID-19 vaccines among patients with advanced chronic kidney disease and kidney failure during the height of the pandemic: a global survey by the International Society of Nephrology.

OBJECTIVE: Patients with advanced chronic kidney disease (CKD) or kidney failure receiving replacement therapy (KFRT) are highly vulnerable to COVID-19 infection, morbidity and mortality. Vaccination is effective, but access differs around the world. We aimed to ascertain the availability, readiness and prioritisation of COVID-19 vaccines for this group of patients globally. SETTING AND PARTICIPANTS: Collaborators from the International Society of Nephrology (ISN), Dialysis Outcomes and Practice Patterns Study and ISN-Global Kidney Health Atlas developed an online survey that was administered electronically to key nephrology leaders in 174 countries between 2 July and 4 August 2021. RESULTS: Survey responses were received from 99 of 174 countries from all 10 ISN regions, among which 88/174 (50%) were complete. At least one vaccine was available in 96/99 (97%) countries. In 71% of the countries surveyed, patients on dialysis were prioritised for vaccination, followed by patients living with a kidney transplant (KT) (62%) and stage 4/5 CKD (51%). Healthcare workers were the most common high priority group for vaccination. At least 50% of patients receiving in-centre haemodialysis, peritoneal dialysis or KT were estimated to have completed vaccination at the time of the survey in 55%, 64% and 51% of countries, respectively. At least 50% of patients in all three patient groups had been vaccinated in >70% of high-income countries and in 100% of respondent countries in Western Europe.The most common barriers to vaccination of patients were vaccine hesitancy (74%), vaccine shortages (61%) and mass vaccine distribution challenges (48%). These were reported more in low-income and lower middle-income countries compared with high-income countries. CONCLUSION: Patients with advanced CKD or KFRT were prioritised in COVID-19 vaccination in most countries. Multiple barriers led to substantial variability in the successful achievement of COVID-19 vaccination across the world, with high-income countries achieving the most access and success.

Executive summary of the KDIGO 2022 Clinical Practice Guideline for Diabetes Management in Chronic Kidney Disease: an update based on rapidly emerging new evidence.

The Kidney Disease: Improving Global Outcomes (KDIGO) 2022 Clinical Practice Guideline for Diabetes Management in Chronic Kidney Disease (CKD) represents a focused update of the KDIGO 2020 guideline on the topic. The guideline targets a broad audience of clinicians treating people with diabetes and CKD. Topic areas for which recommendations are updated based on new evidence include Chapter 1: Comprehensive care in patients with diabetes and CKD and Chapter 4: Glucose-lowering therapies in patients with type 2 diabetes (T2D) and CKD. The content of previous chapters on Glycemic monitoring and targets in patients with diabetes and CKD (Chapter 2), Lifestyle interventions in patients with diabetes and CKD (Chapter 3), and Approaches to management of patients with diabetes and CKD (Chapter 5) has been deemed current and was not changed. This guideline update was developed according to an explicit process of evidence review and appraisal. Treatment approaches and guideline recommendations are based on systematic reviews of relevant studies and appraisal of the quality of the evidence, and the strength of recommendations followed the "Grading of Recommendations Assessment, Development and Evaluation" (GRADE) approach. Limitations of the evidence are discussed, and areas for which additional research is needed are presented.

An ISN-DOPPS Survey of the Global Impact of the COVID-19 Pandemic on Peritoneal Dialysis Services.

Introduction: Home dialysis may minimize SARS-CoV2 exposure risks compared to center-based dialysis. We explored how the pandemic may have introduced challenges related to peritoneal dialysis (PD) supply availability, routine patient care, and how facility practices changed during this time. Methods: The PD/Dialysis Outcomes and Practice Patterns Study (PDOPPS/DOPPS) and International Society of Nephrology (ISN) administered a web-based survey from November 2020 to March 2021. Medical director responses were compared across 10 ISN regions. Results: One hundered sixy-five PD facilities in 51 countries returned surveys. During the initial COVID-19 wave, the reported frequency of in-person patient visits decreased in 9 of 10 ISN regions. Before the pandemic, most facilities required a mask during PD exchanges which continued over the course of the pandemic. Although most facilities in different regions did not report PD supply disruptions, sites in Africa and South Asia reported major disruptions. Reductions in laparoscopic surgical procedures for PD catheters were reported by facilities in 9 of 10 regions whereas nonsurgical percutaneous procedures increased in facilities in 6 regions. Training of new PD patients declined in facilities in each region. Increased use of remote technology by patients to communicate with clinics was observed in all regions compared to prepandemic levels. Conclusion: Marked within-region and across-region variability was noted in PD facility burden, clinical practice, and adaptation to the COVID-19 pandemic. This study highlights opportunities to improve routine PD care, adapt to the ongoing pandemic, and increase preparedness for potential future interruptions in PD care.

Clinical outcomes and performance indicators of patients with kidney failure and acute kidney injuries in ASEAN countries.

INTRODUCTION: This review article reports clinical outcomes and performance indicators of patients with kidney failure (KF) and acute kidney injuries (AKI) in Association of South East Asian Nations (ASEAN) countries. METHODOLOGY: Association of South East Asian Nations data, segregated by income status, from national registries and literature were collated, compared and benchmarked against international references. RESULTS: The national incidence and prevalence of treated KF ranged from 172 to 479 per million population (pmp) and 36-2255 pmp, respectively. Brunei (79%), Malaysia (66%) and Singapore (66%) had world-leading proportions of diabetes-related KF. Hemodialysis (HD), Peritoneal Dialysis (PD) and transplant accounted for 68-100%, 0-27% and 0-18% of all KF replacement therapy, respectively. Transplant patient survival was superior with 90%-93% at 5 years and 71%-90% at 10 years, compared to PD (44%-54%) and HD (53-64%) at 5 years. Higher-income countries were able to achieve good anemia control, HD and PD adequacy targets, while usage of arteriovenous fistula in HD varied from 70% to 85%. Acute Kidney Injury rates ranged from 24.2% to 49.2% of high-dependency admissions. Lower incidences of PD peritonitis and HD catheter-related Bloodstream Infections; and PD-favouring quality-of-life were evident in higher-income countries. CONCLUSION: Association of South East Asian Nations has a challenging burden of kidney disease, with extremely high incidence, prevalence, DM-related KF and AKI rates. The magnitude of the prevailing problem calls for the creation of a regional society under the auspices of ASEAN with a shared perspective of universal, equitable and charitable access to quality renal care; consistent with the founding premises and healthcare initiatives of ASEAN.

The COVID-19 Pandemic Identifies Significant Global Inequities in Hemodialysis Care in Low and Lower-Middle Income Countries-An ISN/DOPPS Survey.

Introduction: It is unknown how the COVID-19 pandemic has affected the care of vulnerable chronic hemodialysis (HD) patients across regions, particularly in low and lower-middle income countries (LLMICs). We aimed to identify global inequities in HD care delivery during the COVID-19 pandemic. Methods: The ISN and the Dialysis Outcomes and Practice Patterns Study (DOPPS) conducted a global online survey of HD units between March and November, 2020, to ascertain practice patterns and access to resources relevant to HD care during the COVID-19 pandemic. Responses were categorized according to World Bank income classification for comparisons. Results: Surveys were returned from 412 facilities in 78 countries: 15 (4%) in low-income countries (LICs), 111 (27%) in lower-middle income countries (LMICs), 145 (35%) in upper-middle income countries (UMICs), and 141 (34%) in high-income countries (HICs). Respondents reported that diagnostic tests for SARS-CoV-2 were unavailable or of limited availability in LICs (72%) and LMICs (68%) as compared with UMICs (33%) and HICs (20%). The number of patients who missed HD treatments was reported to have increased during the COVID-19 pandemic in LICs (64%) and LMICs (67%) as compared with UMICs (31%) and HICs (6%). Limited access to HD, intensive care unit (ICU) care, and mechanical ventilation among hospitalized patients on chronic dialysis with COVID-19 were also reportedly higher in LICs and LMICs as compared with UMICs and HICs. Staff in LLMICs reported less routine testing for SARS-CoV-2 when asymptomatic as compared with UMICs and HICs-14% in LICs and 11% in LMICs, compared with 26% and 28% in UMICs and HICs, respectively. Severe shortages of personal protective equipment (PPE) were reported by the respondents from LICs and LMICs compared with UMICs and HICs, especially with respect to the use of the N95 particulate-air respirator masks. Conclusion: Striking global inequities were identified in the care of chronic HD patients during the pandemic. Urgent action is required to address these inequities which disproportionately affect LLMIC settings thereby exacerbating pre-existing vulnerabilities that may contribute to poorer outcomes.

Peritoneal dialysis fluids.

There have been significant advances in the understanding of peritoneal dialysis (PD) in the last 40 years, and uptake of PD as a modality of kidney replacement therapy is increasing worldwide. PD fluids, therefore, remains the lifeline for patients on this treatment. Developing these fluids to be efficacious in solute clearance and ultrafiltration, with minimal adverse consequences to peritoneal membrane health and systemic effects is a key requirement. Since the first PD fluid produced in 1959, modifications to PD fluids have been made. Nonetheless, the search for that ideal PD fluid remains elusive. Understanding the components of PD fluids is a key aspect of optimizing the successful delivery of PD, allowing for individualized PD prescription. Glucose remains an integral component of PD fluids; however, its deleterious effects continue to be the impetus for the search of an alternative osmotic agent, and icodextrin remains the main alternative. More biocompatible PD fluids have been developed and have shown benefits in preserving residual kidney function. However, high cost and reduced accessibility remain deterrents to its widespread clinical use in many countries. Large-scale clinical trials are necessary and very much awaited to improve the narrow spectrum of PD fluids available for clinical use.

The Global Impact of the COVID-19 Pandemic on In-Center Hemodialysis Services: An ISN-Dialysis Outcomes Practice Patterns Study Survey.

INTRODUCTION: To assess the impact of the COVID-19 pandemic impact on hemodialysis (HD) centers, The Dialysis Outcomes and Practice Patterns Study and ISN collaborated on a web-survey of centers. METHODS: A combined approach of random sampling and open invitation was used between March 2020 and March 2021. Responses were obtained from 412 centers in 78 countries and all 10 ISN regions. RESULTS: In 8 regions, rates of SARS-CoV-2 infection were <20% in most centers, but in North East Asia (NE Asia) and Newly Independent States and Russia (NIS & Russia), rates were ≥20% and ≥30%, respectively. Mortality was ≥10% in most centers in 8 regions, although lower in North America and Caribbean (N America & Caribbean) and NE Asia. Diagnostic testing was not available in 33%, 37%, and 61% of centers in Latin America, Africa, and East and Central Europe, respectively. Surgical masks were widely available, but severe shortages of particulate-air filter masks were reported in Latin America (18%) and Africa (30%). Rates of infection in staff ranged from 0% in 90% of centers in NE Asia to ≥50% in 63% of centers in the Middle East and 68% of centers in NIS & Russia. In most centers, <10% of staff died, but in Africa and South Asia (S Asia), 2% and 6% of centers reported ≥50% mortality, respectively. CONCLUSION: There has been wide global variation in SARS-CoV-2 infection rates among HD patients and staff, personal protective equipment (PPE) availability, and testing, and the ways in which services have been redesigned in response to the pandemic.