Capacity for the management of kidney failure in the International Society of Nephrology South Asia region: report from the 2023 ISN Global Kidney Health Atlas (ISN-GKHA).

The South Asia region is facing a high burden of chronic kidney disease (CKD) with limited health resources and low expenditure on health care. In addition to the burden of CKD and kidney failure from traditional risk factors, CKD of unknown etiologies from India and Sri Lanka compounds the challenges of optimal management of CKD in the region. From the third edition of the International Society of Nephrology Global Kidney Health Atlas (ISN-GKHA), we present the status of CKD burden, infrastructure, funding, resources, and health care personnel using the World Health Organization's building blocks for health systems in the ISN South Asia region. The poor status of the public health care system and low health care expenditure resulted in high out-of-pocket expenditures for people with kidney disease, which further compounded the situation. There is insufficient country capacity across the region to provide kidney replacement therapies to cover the burden. The infrastructure was also not uniformly distributed among the countries in the region. There were no chronic hemodialysis centers in Afghanistan, and peritoneal dialysis services were only available in Bangladesh, India, Nepal, Pakistan, and Sri Lanka. Kidney transplantation was not available in Afghanistan, Bhutan, and Maldives. Conservative kidney management was reported as available in 63% (n = 5) of the countries, yet no country reported availability of the core CKM care components. There was a high hospitalization rate and early mortality because of inadequate kidney care. The lack of national registries and actual disease burden estimates reported in the region prevent policymakers' attention to CKD as an important cause of morbidity and mortality. Data from the 2023 ISN-GKHA, although with some limitations, may be used for advocacy and improving CKD care in the region.

Baclofen-induced myoclonus in patients with renal impairment: A case series.

Baclofen is a derivative of gamma amino butyric acid and is used for control of pain and muscular spasms. It is primarily excreted via the kidneys. In patients with impaired renal functions, the half-life of baclofen is prolonged and symptoms of toxicity can occur with normal doses. Commonly reported symptoms of baclofen toxicity are somnolence, altered mentation, seizures and respiratory depression. Myoclonus secondary to baclofen toxicity is scarcely reported. This case series describes two patients with chronic kidney disease (CKD) who were prescribed regular doses of baclofen for analgesia, and subsequently developed generalized myoclonus. The symptoms resolved with omission of baclofen and haemodialysis. There is currently no consensus on dose modification of baclofen in renal impairment for prevention of adverse neurological events. However, considering the surmounting evidence for low threshold of baclofen toxicity in CKD, dose adjustment protocols or consensus on contraindication need to be established.

Outcomes of COVID-19 in Kidney Transplant Recipients: The Sri Lankan Experience.

Coronavirus disease 2019 (COVID-19) causes severe illness in the immunocompromised. This study aimed to describe the severity and outcomes of kidney transplant recipients (KTRs) treated for COVID-19 during the first 16 months of the pandemic in Sri Lanka. We conducted a cross-sectional survey of all nephrology centers in Sri Lanka using a self-administered electronic data collection sheet. All practicing nephrologists were invited. KTRs who had been treated/were under treatment for COVID-19 between March 1, 2020 and June 30, 2021 were included. Data on patient demographics, management practices, and outcomes were collected. Outcomes included graft loss, requirement of kidney replacement therapy (KRT), duration of hospital stay, highest level of treatment setting, highest level of respiratory support, and mortality. Fifteen nephrologists (12 centers) responded with data regarding 58 KTRs with COVID-19, 10 of whom were receiving ongoing treatment; 47/58 (81%) were male. Forty (69%) were between 30 and 59 years of age and 15 (25.9%) were aged 60 years or above. Fourteen (24.1%) were within 1 year of transplantation. Fifty-three (91.4%) were on triple immunosuppression. Antiproliferative was reduced/withheld in 89.1% and calcineurin inhibitor was reduced/withheld in 42.1%. Overall mortality was 16/48 (33.3%). Seventeen (29.3%) required intensive care. Six (10.3%) received noninvasive ventilation, and 11 (19.0%) received invasive ventilation. Ten of the ventilated patients died. Six needed acute KRT, five of whom died. One patient survived with a loss of graft. There was no association between modifications to the immunosuppression and outcomes. COVID-19 causes poor outcomes and severe illness in KTRs. Special preventive and therapeutic strategies are urgently required.

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.

Corrigendum to A Systematic Review of Renal Pathology in Chronic Kidney Disease of Uncertain Etiology Kidney International Reports Volume 6, Issue 6, June 2021, Pages 1711-1728.

[This corrects the article DOI: 10.1016/j.ekir.2021.03.898.].

Impact of the COVID-19 pandemic on the kidney community: lessons learned and future directions.

The coronavirus disease 2019 (COVID-19) pandemic has disproportionately affected patients with kidney disease, causing significant challenges in disease management, kidney research and trainee education. For patients, increased infection risk and disease severity, often complicated by acute kidney injury, have contributed to high mortality. Clinicians were faced with high clinical demands, resource shortages and novel ethical dilemmas in providing patient care. In this review, we address the impact of COVID-19 on the entire spectrum of kidney care, including acute kidney injury, chronic kidney disease, dialysis and transplantation, trainee education, disparities in health care, changes in health care policies, moral distress and the patient perspective. Based on current evidence, we provide a framework for the management and support of patients with kidney disease, infection mitigation strategies, resource allocation and support systems for the nephrology workforce.

Snakebite Associated Thrombotic Microangiopathy and Recommendations for Clinical Practice.

Snakebite is a significant and under-resourced global public health issue. Snake venoms cause a variety of potentially fatal clinical toxin syndromes, including venom-induced consumption coagulopathy (VICC) which is associated with major haemorrhage. A subset of patients with VICC develop a thrombotic microangiopathy (TMA). This article reviews recent evidence regarding snakebite-associated TMA and its epidemiology, diagnosis, outcomes, and effectiveness of interventions including antivenom and therapeutic plasma-exchange. Snakebite-associated TMA presents with microangiopathic haemolytic anaemia (evidenced by schistocytes on the blood film), thrombocytopenia in almost all cases, and a spectrum of acute kidney injury (AKI). A proportion of patients require dialysis, most survive and achieve dialysis free survival. There is no evidence that antivenom prevents TMA specifically, but early antivenom remains the mainstay of treatment for snake envenoming. There is no evidence for therapeutic plasma-exchange being effective. We propose diagnostic criteria for snakebite-associated TMA as anaemia with >1.0% schistocytes on blood film examination, together with absolute thrombocytopenia (<150 × 109/L) or a relative decrease in platelet count of >25% from baseline. Patients are at risk of long-term chronic kidney disease and long term follow up is recommended.

COVID-19 and Kidney Disease: Progress in Health Inequity From Low-Income Settings.

The acute coronavirus disease-2019 (COVID-19) pandemic has had a significant impact on the incidence and prevalence of acute kidney injury and chronic kidney disease globally and in low-income settings. Chronic kidney disease increases the risk of developing COVID-19 and COVID-19 causes acute kidney injury directly or indirectly and is associated with high mortality in severe cases. Outcomes of COVID-19-associated kidney disease were not equitable globally owing to a lack of health infrastructure, challenges in diagnostic testing, and management of COVID-19 in low-income settings. COVID-19 also significantly impacted kidney transplant rates and mortality among kidney transplant recipients. Vaccine availability and uptake remains a significant challenge in low- and lower-middle-income countries compared with high-income countries. In this review, we explore the inequities in low- and lower-middle-income countries and highlight the progress made in the prevention, diagnosis, and management of patients with COVID-19 and kidney disease. We recommend further studies into the challenges, lessons learned, and progress made in the diagnosis, management, and treatment of patients with COVID-19-related kidney diseases and suggest ways to improve the care and management of patients with COVID-19 and kidney disease.

Access to Dialysis for Acute Kidney Injury in Low-Resource Settings.

Acute kidney injury (AKI) is estimated to occur in approximately 13.3 million patients per year with an estimated mortality of 1.7 million. Approximately 85% of cases occur in low-resource settings where access to kidney replacement therapy (KRT) may be limited or nonexistent. The true extent of AKI, including access to KRT in developing countries, is largely unknown because appropriate systems are not in place to detect AKI or report it. Barriers to provision of KRT in low-resource settings revolve around systems management and funding, however, there also are region-specific issues. This review focuses on the epidemiology, obstacles, and solutions to improving access to KRT for AKI.

Serum and urinary biomarkers for early detection of acute kidney injury following Hypnale spp. envenoming.

BACKGROUND: Hump-nosed pit viper (HNV; Hypnale spp.) bites account for most venomous snakebites in Sri Lanka. Acute kidney injury (AKI) is the most serious systemic manifestation (1-10%) following HNV envenoming. We aimed to identify the value of functional and injury biomarkers in predicting the development of AKI early following HNV bites. METHODS: We conducted a prospective cohort study of patients with confirmed HNV envenoming presenting to two large tertiary care hospitals in Sri Lanka. Demographics, bite details, clinical effects, complications and treatment data were collected prospectively. Blood and urine samples were collected from patients for coagulation and renal biomarker assays on admission, at 0-4h, 4-8h, 8-16h and 16-24h post-bite and daily until discharge. Follow-up samples were obtained 1 and 3 months post-discharge. Creatinine (sCr) and Cystatin C (sCysC) were measured in serum and kidney injury molecule-1 (uKIM-1), clusterin (uClu), albumin (uAlb), ß2-microglobulin (uß2M), cystatin C (uCysC), neutrophil gelatinase associated lipocalin (uNGAL), osteopontin (uOPN) and trefoil factor-3 (uTFF-3) were measured in urine. Definite HNV bites were based on serum venom specific enzyme immunoassay. Kidney Disease: Improving Global Outcomes (KDIGO) criteria were used to stage AKI. Two patients had chronic kidney disease at 3 month follow-up, both with pre-existing abnormal sCr, and one developed AKI following HNV envenoming. RESULTS: There were 52 patients with confirmed HNV envenoming; median age 48y (Interquartile range [IQR]:40-59y) and 29 (56%) were male. Median time to admission was 1.87h (IQR:1-2.75h). Twelve patients (23%) developed AKI (AKI stage 1 = 7, AKI stage 2 = 1, AKI stage 3 = 4). Levels of five novel biomarkers, the functional marker serum Cystatin C and the damage markers urinary NGAL, cystatin C, ß2-microglobulin and clusterin, were elevated in patients who developed moderate/severe acute kidney injury. sCysC performed the best at 0-4 h post-bite in predicting moderate to severe AKI (AUC-ROC 0.95;95%CI:0.85-1.0) and no biomarker performed better than sCr at later time points. CONCLUSIONS: sCysC appears to be a better marker than sCr for early prediction of moderate to severe AKI following HNV envenoming.

A Systematic Review of Renal Pathology in Chronic Kidney Disease of Uncertain Etiology.

INTRODUCTION: Despite much research on chronic kidney disease of uncertain etiology (CKDu) in Sri Lanka and the Mesoamerican nephropathy, the etiology and pathogenesis of this disease remains elusive. The pathology has broadly been described as chronic tubulointerstitial nephritis and no specific signature lesions have been identified. METHODS: A scoping review was conducted through MEDLINE and Google Scholar databases for peer-reviewed publications on biopsy studies related to CKDu - Sri Lanka and Mesoamerican nephropathy to develop a comparative and critical analysis of the renal pathology found in these patients. RESULTS: Thirteen studies met the selection criteria. Interstitial fibrosis was the predominant lesion in all the studies. Tubulointerstitial and glomerular abnormalities showed a more variable distribution. No characteristic histopathological feature was reported other than a proximal tubular lysosomal inclusion body which was claimed to indicate a toxic etiology. Three main pathogenetic mechanisms were postulated: repeated acute insults leading to scarring, low-grade chronic insults leading to non-inflammatory fibrosis, and tubulointerstitial damage in combination with glomerular injury. The main limitations in the interpretation and comparative analysis of these studies were the heterogeneity in case selection and biopsy reporting. CONCLUSIONS: Although no characteristic histopathological feature could be found in CKDu-Sri Lanka or Mesoamerican nephropathy, there are noticeable differences between these two groups in the frequency and severity of the glomerular and tubulointerstitial changes which warrant more explorative studies preferably on kidneys in early stages of the disease. Future strategies should ensure that more uniform selection criteria and reporting methods are used.

International Society of Nephrology Global Kidney Health Atlas: structures, organization, and services for the management of kidney failure in South Asia.

Information about disease burden and the available infrastructure and workforce to care for patients with kidney disease was collected for the second edition of the International Society of Nephrology Global Kidney Health Atlas. This paper presents findings for the 8 countries in the South Asia region. The World Bank categorizes Afghanistan and Nepal as low-income; Bangladesh, Bhutan, India, and Pakistan as lower-middle-income; and Sri Lanka and the Maldives as upper-middle-income countries. The prevalence of chronic kidney disease (CKD) in South Asia ranged from 5.01% to 13.24%. Long-term hemodialysis and long-term peritoneal dialysis are available in all countries, but Afghanistan lacks peritoneal dialysis services. Kidney transplantation was available in all countries except Bhutan and Maldives. Hemodialysis was the dominant modality of long-term dialysis, peritoneal dialysis was more expensive than hemodialysis, and kidney transplantation overwhelmingly depended on living donors. Bhutan provided public funding for kidney replacement therapy (dialysis and transplantation); Sri Lanka, India, Pakistan, and Bangladesh had variable funding mechanisms; and Afghanistan relied solely on out-of-pocket expenditure. There were shortages of health care personnel across the entire region. Reporting was variable: Afghanistan and Sri Lanka have dialysis registries but publish no reports, whereas Bangladesh has a transplant registry. South Asia has a large, but poorly documented burden of CKD. Diabetes and hypertension are the major causes of CKD throughout the region with a higher prevalence of infectious causes in Afghanistan and a high burden of CKD of an unknown cause in Sri Lanka and parts of India. The extent and quality of care delivery is suboptimal and variable. Sustainable strategies need to be developed to address the growing burden of CKD in the region.