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.

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.

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.

Severe acute kidney injury following Sri Lankan Hypnale spp. envenoming is associated with thrombotic microangiopathy.

CONTEXT: Acute kidney injury (AKI) is the most serious clinical manifestation of the Sri Lankan hump-nosed pit viper (Hypnale spp.) bites. Thrombotic microangiopathy (TMA) is increasingly recognized in association with AKI in cases of Hypnale spp envenomation. We investigated AKI in a cohort of cases of Hypnale envenomation, its association with TMA and the early diagnostic value of common biomarkers for AKI occurring. MATERIALS AND METHODS: We conducted a prospective observational study of suspected viper bites and included 103 confirmed cases of Hypnale envenomation, based on venom specific enzyme immunoassay of blood. AKI was defined using the Kidney Disease: Improving Global Outcomes (KDIGO) criteria. Thrombotic microangiopathy was diagnosed based on thrombocytopenia (platelet count < 150,000 × 103/µL) and microangiopathic haemolytic anaemia (MAHA). We investigated the diagnostic performance of creatinine, platelet count and INR for AKI within 4 h and 8 h post-bite by area under the receiver operator characteristic curve (AUC-ROC). RESULTS: Ten patients developed AKI: seven AKI stage 1 and three AKI stage 3. Ten patients (10%) developed thrombocytopaenia while 11 (11%) had MAHA. All three AKI stage 3 had thrombocytopaenia and MAHA fulfilling the criteria for TMA. Two of them presented with oliguria/anuria and all three required haemodialysis. Serum creatinine within 4 h post-bite was the best predictor of AKI with AUC-ROC of 0.83 (95% CI: 0.67-0.99) and was no better within 8 h of the bite. CONCLUSIONS: We found that AKI is uncommon in Hypnale spp. envenomation, but an important serious complication. Severe AKI was associated with TMA. A creatinine within 4 h post-bite was the best predictor of AKI.

Thrombotic microangiopathy and acute kidney injury following Sri Lankan Daboia russelii and Hypnale species envenoming.

Context: Thrombotic microangiopathy (TMA) resulting in acute kidney injury (AKI) is an important complication of venomous snakebites. We aimed to describe TMA secondary to Russell's viper (Daboia russelli) and hump-nosed viper (Hypnale spp.) bites and assess the effect of different treatments.Materials and methods: We undertook a prospective observational study of patients with AKI secondary to snakebite over a two-year period. Data recorded included: demographic details, clinical and laboratory features, treatment, complications and outcomes, until hospital discharge and at three months post-discharge. TMA was defined as the development of microangiopathic hemolytic anemia and thrombocytopenia along with AKI. Treatment with therapeutic plasma exchange (TPE; also known as plasmapheresis) and/or fresh frozen plasma (FFP) was determined by the treating clinician. Antivenom was given to all patients with evidence of systemic envenoming following Russell's viper bites.Results: Fifty-nine patients were included in the analysis. Thirty-three (56%) were males and median age was 56 years. Forty-five (76%) developed TMA while a further 11 and two developed isolated thrombocytopenia and microangiopathic hemolytic anemia, respectively. Presence of TMA was associated with increased dialysis requirements (5 vs. 3) and longer hospital stay (18 vs. 12 days). Of the patients with TMA, nine received TPE with or without FFP infusions. The use of TPE was not associated with improved outcomes in patients with TMA based on requirement for blood transfusion, recovery of thrombocytopenia, requirement of dialysis and duration of hospital stay. Patients who did not receive TPE had better renal function at three months compared to patients who received this treatment.Conclusion: Presence of TMA in patients with Daboia and Hypnale bites was associated with a more prolonged course of AKI. Patients with TMA who were treated with TPE did not have improved early or late outcomes compared to patients who were not treated with TPE.

CKD of Unknown Etiology (CKDu) in Sri Lanka: A Multilevel Clinical Case Definition for Surveillance and Epidemiological Studies.

Emergence of a new form of chronic kidney disease (CKD) of unknown etiology (CKDu) during the last 2 decades has resulted in considerable morbidity and mortality among the agricultural community residing in the north central region of Sri Lanka. A 3-level epidemiological case definition to identify CKDu in Sri Lanka was developed and published by the Ministry of Health in November 2016. The Sri Lanka Society of Nephrology (SLSON) refined the definition through a consensus of experts using a systematic approach in August 2017. An initial consultative meeting with the participation of 31 experts, including nephrology specialists, experts on primary care and epidemiology, and policy and university academics with long-standing experience in CKDu research, was held to identify the gaps in the existing definition. Following the meeting, a facilitator conducted 2 rounds of remote consultations using the Delphi method to obtain consensus of the participants on suggestions to improve the existing case definition. The process was initiated in August 2017 and was completed in April 2018 and resulted in the participants agreeing to a refined multilevel clinical case definition for CKDu to be used in surveillance and epidemiological studies. This article describes the process used and development of this new case definition for CKDu in Sri Lanka.

Star fruit nephrotoxicity: a case series and literature review.

BACKGROUND: Star fruit is a popular medicinal fruit in the tropics. Its hypoglycaemic properties are considered useful in achieving glycaemic control in diabetes. Star fruit induced nephrotoxicity is a rare cause of acute kidney injury in individuals with both normal and reduced baseline renal function. We present three cases of acute kidney injury due to star fruit nephrotoxicity from Sri Lanka, and discuss the published literature on this topic. CASE PRESENTATION: Three Sri Lankan patients, all with a background of diabetes, presented to us with acute nausea and anorexia following recent consumption of star fruit. Two patients complained of diarrhoea and one patient complained of intractable hiccoughs. They all had elevated serum creatinine on admission. Two were known to have normal baseline serum creatinine levels. On renal biopsy two had evidence of oxalate crystal deposition. One did not show crystal deposition but had acute interstitial nephritis for which no alternate cause could be identified. Two were treated with short courses of prednisolone and two required acute haemodialysis. All recovered renal function, with both patients with known baselines approaching their premorbid serum creatinine levels. CONCLUSION: Consumption of star fruit, especially on an empty stomach or in a state of dehydration may precipitate acute kidney injury. A history of star fruit ingestion must be actively looked for in patients presenting with unexplained acute kidney injury. The use of star fruit as a therapy for diabetes should be discouraged.

Determination of the sub-lethal nephrotoxic dose of Russell's viper (Daboia russelii) venom in Wistar rats.

Wistar rats were administered increasing doses of Russell's viper venom (RVV; 0.025-0.4 mg/kg) intraperitoneally to investigate acute kidney injury (AKI) by measuring creatinine (1.5-fold increase in serum creatinine above baseline) and examining kidney histology. Approximately 50% of rats receiving 0.25-0.4 mg/kg venom died within 72 h. An increase in serum creatinine only occurred at a venom dose of 0.4 mg/kg, except in two rats. Acute tubular necrosis, glomerular necrosis, cortical necrosis and interstitial inflammation were observed at venom doses of ≥0.25 mg/kg in 12/36 rats. However, of those 12 rats only four survived to 48 h compared to the 24 rats not developing nephrotoxicity, in which 18 were alive at 48 h. There was poor correlation between histological nephrotoxicity and AKI based on creatinine measurement. The early death in rats with AKI makes this a poor model for studying RVV-induced AKI.

Descriptive analysis of glomerulonephritis by histological type and their progression among adults in a tertiary care center in Sri Lanka.

Prevalence of different glomerulonephritides and their clinical course vary geographically. Our objectives are to assess the prevalence of different histological types of glomerulonephritis (GN) based on the light microscopic histology and to assess their progression according to histological type. A retrospective cross-sectional study was carried out among adult patients (>18 years) with a histological diagnosis of GN at the University Professorial Unit over a period of six months. Information including demographic data, renal biopsy findings, and progression of the disease through serum creatinine (SCr) level were collected through existing clinic records of consenting patients. Data were analyzed by Statistical Package for the Social Sciences. There were 109 patients (females = 90) with a mean age of 40.32 ± 15.24 years. The most common histological type was focal segmental glomerulosclerosis (FSGS) in 27 (24.8%) followed by minimal change disease in 25 (22.9%), mesangioproliferative glomerulonephritis (MesPGN) in 18 (16.5%), membranoproliferative glomerulonephritis in six (5.5%), membranous glomerulonephritis in three patients (2.8%), and crescentic GN in one patient (0.9%). There was a statistically significant rise in SCr level at seven years from the initial presentation in the histological types; FSGS [P = 0.04; 95% confidence interval (CI) = 0.06-1.0] and MesPGN (P = 0.03; 95% CI = 0.3-0.9). Focal segmental glomerulosclerosis was the most common histology type in the population studied. There was a statistically significant progression of FSGS and MesPGN.

Incidences and clinical outcomes of acute kidney injury in ICU: a prospective observational study in Sri Lanka.

BACKGROUND: Acute kidney injury (AKI) is a common and a serious complication among patients admitted to intensive care units (ICUs), and has been the focus of many studies leading to recent advances in diagnosis and classification. The incidence and outcome of AKI in Sri Lankan ICUs is largely unknown. The aim of this study was to describe the incidence, severity and outcome of AKI among patients admitted to the medical ICU, National Hospital, Colombo, Sri Lanka (NHSL). METHODS: Patients admitted to the medical ICU, NHSL, over a period of 6 months were studied prospectively.Standard demographic, physiological and clinical data were collected. Severity of illness was assessed using SOFA (Sequential Organ Failure Assessment) score. Diagnosis of AKI was based on Acute Kidney Injury Network (AKIN) criteria. RESULTS: Of 212 patients screened, 108 satisfied the inclusion criteria; males 67(61.5%); mean age 47.8 years(SD 19.4, range 12-94). Mean duration of ICU stay was 11.6 days (SD 10.6, range 2-55). Eighty one (75.0%) received mechanical ventilation. Forty nine (45.4%) had sepsis. ICU mortality was 38.9% and AKI was present in 60.2%. The majority of AKI patients (38, 58.5%) had AKI stage 3. Patients with AKI were at higher risk of death (p < 0.01). Neither age, gender, nor the presence of co-morbidities were associated with increased risk of AKI. Patients with AKI had significantly longer ICU stay (Log-Rank Chi Square: 23.186, p < 0.0001). Both the incidence of AKI and ICU mortality were higher in patients with SOFA scores over 9 (Pearson Chi-Square 7.581, p = 0.006, and 11.288, p = 0.001 respectively). CONCLUSIONS: The incidence of AKI is high at 60% among our ICU patients, and those with AKI had higher mortality and longer duration of ICU stay. Age, gender or the presence of co-morbidities was not associated with a higher risk of AKI. Patients with SOFA scores over 9 within the first 24 hours were more likely to develop AKI and had higher risk of death.

Acute tubular necrosis in a patient with paroxysmal nocturnal hemoglobinuria.

Acute renal failure (ARF) is a well-recognized complication of paroxysmal nocturnal hemoglobinuria (PNH). The predominant mechanism is intravascular hemolysis resulting in massive hemoglobinuria ARF. We report a case of acute tubular necrosis (ATN) developed in the absence of overwhelming evidence of intravascular hemolysis in a 21-year-old man with anemia, who was eventually diagnosed to have PNH. The patient presented with rapidly deteriorating renal functions in the background of iron deficiency anemia, which was attributed to reflux esophagitis. There was no clinical or laboratory evidence of intravascular hemolysis. Renal biopsy revealed ATN with deposition of hemosiderin in the proximal tubular epithelial cells. Diagnosis of PNH was confirmed with a positive Ham's test and flow cytometry. Our case emphasizes the need to consider ATN as a possible cause for ARF in patients suspected to have PNH even in the absence of overwhelming evidence of intravascular hemolysis.

Epidemiology of chronic kidney disease in a Sri Lankan population: experience of a tertiary care center.

Chronic kidney disease (CKD) is a growing problem in Sri Lanka. Diabetes and hypertension are the main contributors to the disease burden. A new form of CKD of uncertain etiology (CKD-u) is the predominant form of CKD in certain parts of Sri Lanka, threatening to reach epidemic proportions. A cross-sectional descriptive study was carried out over a three-month period at the National Hospital of Sri Lanka to identify the underlying etiologic factors for the disease in a cohort of patients with CKD. A total of 200 patients were studied with a mean age of 50.57 years. Of them, 108 (54%) were in CKD stage V. Majority of the patients were from the western province (137, 68.5%) with only five (2.5%) from provinces with high prevalence of CKD-u. The most common underlying causes of CKD were diabetes (88, 44%) and hypertension (34, 17%). However, in patients younger than 40 years of age the most common cause was glomerulonephritis (20, 42.6%). Diabetes was the most common cause of CKD among patients from the western province (74, 54%). The prevalence of CKD-u was twice as high in patients from areas outside the western province compared with patients from this province (P > 0.05). The low prevalence of CKD-u in the study population could be the result of poor representation of patients from provinces with high prevalence of CKD-u.

Non-dialytic management of sepsis-induced acute kidney injury.

Sepsis is an important cause of morbidity and mortality. Acute Kidney Injury (AKI) often complicates sepsis, leading to greater complexity, higher cost of care and worsening prognosis. Despite the improved understanding of its underlying pathophysiological basis, there have been very few interventions, which have consistently been shown to be of value in the management of sepsis-induced AKI. Measures such as adequate hydration, maintenance of adequate circulating blood volume and mean arterial pressure, and avoidance of nephrotoxins, are still the mainstay of prevention. Loop diuretics, mannitol and "low dose" dopamine have been clearly shown to be of no value in the prevention or treatment of AKI and may, in fact, do harm. Among the remaining pharmacological options, N-acetylcysteine (NAC) may have a role in the prevention of radiocontrast induced AKI.