18-month longitudinal SARS COV-2 neutralizing antibody dynamics in haemodialysis patients receiving heterologous 3-dose vaccination (AZD-1222- AZD-1222- BNT162b2) in a lower middle income setting.

BACKGROUND: Patients with chronic kidney disease on haemodialysis (HD) were given priority COVID-19 vaccination due to increased disease risk. The immune response to COVID-19 vaccination in patients on HD was diminished compared to healthy individuals in 2-dose studies. This study aimed to evaluate seroconversion rate, neutralizing antibody (nAB) levels and longitudinal antibody dynamics to 3-dose heterologous vaccination against COVID-19 in a cohort of HD patients compared to healthy controls and assess patient factors associated with antibody levels. METHODS: This study was a case-control longitudinal evaluation of nAB dynamics in 74 HD patients compared to 37 healthy controls in a low/middle income setting. Corresponding samples were obtained from the two cohorts at time-points (TP) 1-1-month post 2nd dose of AZD1222 vaccine, TP2- 4 months post 2nd dose, TP4- 2 weeks post 3rd dose with BNT162b2 vaccine, TP5-5 months post 3rd dose and TP6-12 months post 3rd dose. Additional data is available at TP0- pre 2nd dose and TP3- 6 months post 2nd dose in HC and HD cohorts respectively. Anti-SARS-CoV-2 nAB were detected using Genscript cPassTM pseudoviral neutralization kit. Demographic and clinical details were obtained using an interviewer administered questionnaire. RESULTS: Cohorts were gender matched while mean age of the HD cohort was 54.1yrs (vs HCs mean age, 42.6yrs, p < 0.05). Percentage seroconverted and mean/median antibody level (MAB) in the HD cohort vs HCs at each sampling point were, TP1-83.7% vs 100% (p < 0.05), MAB-450 IU/ml vs 1940 IU/ml (p < 0.0001); TP2-71.4% vs 100%, (p < 0.001), MAB- 235 IU/ml vs 453 IU/ml, (p < 0.05); TP4-95.2% vs 100% (p > 0.05), MAB-1029 IU/ml vs 1538 IU/ml (p < 0.0001); TP5-100% vs 100%, MAB-1542 IU/ml vs 1741IU/ml (p > 0.05); TP6-100% vs 100%, MAB-1961 IU/ml vs 2911 IU/ml (p > 0.05). At TP2, patients aged < 60 years (p < 0.001) were associated with maintaining seropositivity compared to patients > 60 years. CONCLUSION: Two dose vaccination of haemodialysis patients provided poor nAB levels which improved markedly following 3rd dose vaccination, the effect of which was long- lasting with high nAB levels in both patients and controls detectable at 1 year follow-up.

The pattern of cytomegalovirus replication in post-renal transplant recipients with pre-emptive therapy strategy during the 1st year of post-transplantation.

Objectives: The prevalence and reactivating pattern of cytomegalovirus (CMV) among renal transplant recipients in Sri Lanka is scarce. The study was aimed to describe the replication patterns of CMV in post-renal transplant recipients who were on pre-emptive therapy and identify the risk factors and time period for CMV reactivating during the 1st year of transplantation and provide an insight into the selection of pre-emptive therapy in the local setting. Methods: A retrospective and cohort study was conducted, enrolling renal transplant recipients who have completed routine 1-year follow-up for pre-emptive management at the National Hospital, Kandy, from January 2016 to January 2021. CMV quantitative polymerase chain reaction results and demographic data of enrolled recipients were analyzed to investigate the CMV replication pattern and risk factors. Categorical data were analyzed using Pearson's Chi-square test, considering P < 0.05 statistically significant. Continuous variables were presented as percentages. Results: Two hundred and fifty-one renal transplant recipients' data were included in the study. Of them, 75.70% were male patients, and the mean age of the study population was 43.25 years. CMV DNAemia incidence was 56.57% during the 1st year of post-renal transplantation. Only 9.16% had developed more than 104 IU/mL or significant DNAemia. Sex and donor type were not risk factors for CMV reactivation. However, the recipient's age was significantly associated with CMV viraemia among renal transplant recipients. Conclusion: Considering the low incidence of significant viraemia among the study population, pre-emptive treatment would be the cost-effective strategy for management of the post-renal transplant recipients in local settings.

Leptospirosis: A Potential Culprit for Chronic Kidney Disease of Uncertain Etiology.

PURPOSE: Chronic kidney disease of uncertain etiology (CKDu) is an environmental nephropathy in which the etiological factors are yet uncertain. Leptospirosis, a spirochetal infection that is common among agricultural communities, has been identified as a potential etiology for CKDu beyond environmental nephropathy. Although CKDu is a chronic kidney disease, in endemic regions, an increasing number of cases are reported with features suggestive of acute interstitial nephritis without any known reason (AINu), with or without background CKD. The study hypothesizes that exposure to pathogenic leptospires is one of the causative factors for the occurrence of AINu. METHOD: This study was carried out using 59 clinically diagnosed AINu patients, 72 healthy controls from CKDu endemic region (endemic controls [ECs]), and 71 healthy controls from CKDu non-endemic region (non-endemic controls [NECs]). RESULTS: The seroprevalence of 18.6, 6.9, and 7.0% was observed in the AIN (or AINu), EC, and NEC groups, respectively, from the rapid IgM test. Among 19 serovars tested, the highest seroprevalence was observed at 72.9, 38.9, and 21.1% in the AIN (AINu), EC, and NEC groups, respectively, by microscopic agglutination test (MAT), particularly for serovar Leptospira santarosai serovar Shermani. This emphasizes the presence of infection in AINu patients, and this also suggests that Leptospira exposure might play an important role in AINu. CONCLUSION: These data suggest that exposure to Leptospira infection could be one of the possible causative factors for the occurrence of AINu, which may lead to CKDu in Sri Lanka.

Randomized control trial of prednisolone and doxycycline in patients with acute interstitial nephritis of unknown aetiology.

BACKGROUND: Patients presenting with acute interstitial nephritis (AIN) of unknown aetiology, probably the earliest presentation of chronic kidney disease of unknown aetiology (CKDu), have been treated with oral prednisolone and doxycycline by physicians in Sri Lanka. This trial assessed the effectiveness of prednisolone and doxycycline based on eGFR changes at 6 months in patients with AIN of unknown aetiology. METHOD: A randomized clinical trial with a 2 × 2 factorial design for patients presenting with AIN of unknown aetiology (n = 59) was enacted to compare treatments with; A-prednisolone, B-doxycycline, C-both treatments together, and D-neither. The primary outcome was a recovery of patients' presenting renal function to eGFR categories: 61-90 ml/min/1.73m2 (complete remission- CR) to 31-60 ml/min/1.73m2 (partial remission- PR) and 0-30 ml/min/1.73m2 no remission (NR) by 6 months. A secondary outcome was progression-free survival (not reaching < 30 ml/min/1.73m2 eGFR), by 6-36 months. Analysis was by intention to treat. RESULTS: Seventy patients compatible with a clinical diagnosis of AIN were biopsied for eligibility; 59 AIN of unknown aetiology were enrolled, A = 15, B = 15, C = 14 and D = 15 randomly allocated to each group. Baseline characteristics were similar between groups. The number of patients with CR, PR and NR, respectively, by 6 months, in group A 3:8:2, group B 2:8:3 and group C 8:5:0 was compared with group D 8:6:1. There were no significant differences found between groups A vs. D (p = 0.2), B vs. D (p = 0.1) and C vs. D (p = 0.4). In an exploratory analysis, progression-free survival in prednisolone-treated (A + C) arms was 0/29 (100%) in comparison to 25/30 (83%) in those not so treated (B + D) arms, and the log-rank test was p = 0.02, whereas no such difference found (p = 0.60) between doxycycline-treated (B + C) arms 27/29 (93%) vs those not so treated (A + D) arms 27/30 (90%). CONCLUSION: Prednisolone and doxycycline were not beneficial for the earliest presentation of CKDu at 6 months. However, there is a potential benefit of prednisolone on the long-term outcome of CKDu. An adequately powered steroid trial using patients reaching < 30 ml/min/1.73m2 eGFR by 3 years, as an outcome is warranted for AIN of unknown aetiology. TRIAL REGISTRATION: Sri Lanka Clinical Trial Registry SLCTR/2014/007, Registered on the 31st of March 2014.

Overcoming barriers and building a strong peritoneal dialysis programme - Experience from three South Asian countries.

The development of peritoneal dialysis (PD) programmes in lower-resource countries is challenging. This article describes the learning points of establishing PD programmes in three countries in South Asia (Nepal, Sri Lanka and Pakistan). The key barriers identified were government support (financial), maintaining stable supply of PD fluids, lack of nephrologist and nurse expertise, nephrology community bias against PD, lack of nephrology trainee awareness and exposure to this modality. To overcome these barriers, a well-trained PD lead nephrologist (PD champion) is needed, who can advocate for this modality at government, professional and community levels. Ongoing educational programmes for doctors, nurses and patients are needed to sustain the PD programmes. Support from well-established PD centres and international organisations (International Society of Peritoneal Dialysis (ISPD), International Society of Nephrology (ISN), International Pediatric Nephrology Association (IPNA) are essential.

Pilot Study of Renal Urinary Biomarkers for Diagnosis of CKD of Uncertain Etiology.

INTRODUCTION: Chronic kidney disease of uncertain etiology (CKDu), an emerging chronic kidney disease (CKD) subtype, contributes to significant morbidity and mortality in certain tropical countries. Although several indicators of CKDu have been previously suggested, sensitive and specific tests to detect early disease or predict disease progression are currently unavailable. This study focused on evaluating 8 renal urinary markers, namely neutrophil gelatinase-associated lipocalin (NGAL), Kidney Injury Molecule-1 (KIM1), cystatin C (CST3), beta 2 microglobulin (B2M), osteopontin (OPN), alpha 1 microglobulin (A1M), tissue inhibitor of metalloproteinase 1 (TIMP1), and retinol binding protein 4 (RBP4), with the hypothesis that these have distinct expression patterns in patients with CKDu. METHODS: A cross-sectional study was conducted with 5 study groups comprising subjects from CKDu, endemic CKD, nonendemic CKD, and endemic healthy and nonendemic healthy controls. The urinary levels of the 8 selected renal biomarkers were quantified using multiplex biomarker assay, and the data were subjected to systematic analysis using logistic regression algorithm aiming to extract the best marker combination that could distinctly identify the disease groups noninvasively from the healthy controls. RESULTS: A 3-marker signature panel comprising A1M, KIM1, and RBP4 was identified to represent the best minimum marker combination for differentiating all CKD categories, including CKDu, from healthy controls with an overall sensitivity of ≥0.867 and specificity ≥0.765. The marker combination comprising OPN, KIM1, and RBP4 showed high predictive performance for distinguishing patients with CKDu from patients with CKD with both sensitivity and specificity ≥0.93, which was superior to any existing noninvasive indicator. CONCLUSION: In all, our systematic evaluation of urinary markers previously linked to CKD, in general, allowed identification of exclusive marker panel combination for early diagnosis and confirmation of CKDu.

Expanding CAPD in Low-Resource Settings: A Distance Learning Approach.

BACKGROUND: Despite growing need, treatment for end-stage renal disease is limited in low- and middle-income countries due to resource restraints. We describe the development of an educational curriculum and quality improvement program to support continuous ambulatory peritoneal dialysis (CAPD) performed primarily by non-nephrology providers in Sri Lanka. METHODS: We developed a program of education, outcome tracking, and expert consultation to support providers in Kandy, Sri Lanka. Education included videos and in-person didactics covering core topics in CAPD. Event-tracking sheets recorded root causes and management of infections and hospitalizations. Conferences reviewed clinical cases and overall clinic management. We evaluated the patient census, peritonitis rates, and root causes and management of infections over 1 year. RESULTS: The curriculum was published through the International Society of Nephrology online academy. High provider turnover limited curriculum assessments. The CAPD patient census rose from 63 to 116 during the year. The peritonitis rate declined significantly, from 0.8 episodes per patient-year in the first 6 months to 0.4 in the latter 6 months, though the most common root causes of peritonitis, related to contamination events and hygiene, persisted. The appropriate ascertainment of culture data and prescription of antibiotics also increased. CONCLUSIONS: Our project supported the expansion of a CAPD program in a resource-limited setting, while also improving peritonitis outcomes. Ongoing challenges include ensuring a durable educational system for rotating providers, tracking outcomes beyond peritonitis, and formalizing management protocols. Our program can serve as an example of how established dialysis programs can support the burgeoning work of providers in resource-limited setting.

Clinicopathological findings, treatment response and predictors of long-term outcome in a cohort of lupus nephritis patients managed according to the Euro-lupus regime: a retrospective analysis in Sri Lanka.

BACKGROUND: Despite the improvement in survival of patients with lupus nephritis (LN) globally, there is sparse data from Sri Lanka (SL). The current study aims to describe the clinicopathological findings, treatment response and predictors of long-term outcome of patients with WHO class III-IV LN in SL, managed according to the Euro-lupus regime. RESULTS: Of 72 patients, 64 were females. In half of them, LN was diagnosed within the 1st year of the illness. The most common presenting feature was sub-nephrotic proteinuria. Sixteen and twenty patients had nephrotic syndrome and abnormal renal function respectively at the time of diagnosis. Fifty-four patients (75%) responded to the Euro-lupus regimen [CR, 20 (28%); PR, 34(47%)]. Later at 6 months, 65 patients (90%) achieved remission [CR, 31(43%); PR, 34 (47%)]. Seven patients experienced treatment failure. During the total duration of follow up, 54 patients remained in complete or partial remission, 26 developed renal relapses, and 19 suffered severe infective episodes. Renal relapses were more common in people who achieved partial remission than complete remission. The long term renal outcome was not associated with age, sex, severity of proteinuria, class of LN or initial renal function. Patients who achieved remission at 6 months had a good long-term outcome. CONCLUSIONS: The demographic and clinical features of WHO class III and IV LN in Sri Lankan patients were similar to that reported in the global literature. 75% of patients responded to the Euro-lupus regimen. Therefore, this regime is a suitable initial regimen for LN patients in SL. Good long-term renal outcome can be predicted by early response to therapy. Further studies are necessary to explore better treatment options for patients who fail to achieve remission during initial therapy.

Chronic kidney disease of uncertain etiology in Sri Lanka is a possible sequel of interstitial nephritis!

INTRODUCTION: The majority of published data on chronic kidney disease of uncertain etiology (CKDu) is on asymptomatic patients who were detected in screening programs. The clinicopathological profile of a group of patients presenting with acute symptoms and renal dysfunction from CKDu endemic regions in Sri Lanka was studied. METHODS: 59 patients > 10 years of age with backache, feverish fatigue feeling, dysuria, joint pain, or dyspepsia, singly or in combination with elevated serum creatinine (> 116 and > 98 µmol/L for male and females, respectively) were included in the study. Those patients who had normal-sized kidneys were biopsied after excluding clinically detectable causes for renal dysfunction. Histology was scored with activity and chronicity indices. These patients' urinary sediment and inflammatory markers were checked. Patients were stratified into three groups based on duration of symptom onset to the time of biopsy. The natural course of the disease was described using serial mean serum creatinine and histological activity as well as chronicity indices in these 3 groups. RESULTS: These patients' mean age, occupation, and sex ratio were 44 (9) years, 57 farmers, and male : female 55 : 4, respectively. Mean serum creatinine at biopsy was 143.8 (47.9) µmol/L. Elevated inflammatory markers and active urine sediment were reported. Histology was compatible with an interstitial nephritis with a mixture of acute and chronic tubulointerstitial lesions and glomerular scarring. In the natural course of an acute episode of CKDu, serum creatinine and histological activity were reduced while histological chronicity increased. CONCLUSION: CKDu may be preceded by an acute episode of tubulointerstitial nephritis (TIN).

Mantle cell lymphoma first presenting as immune complex-mediated glomerulonephritis: a case report.

INTRODUCTION: Kidney involvement in non-Hodgkin lymphoma is recognized but mostly diagnosed following a diagnosis of lymphoma. We describe a rare case of mantle cell lymphoma, a B-cell-type non-Hodgkin lymphoma, first presenting with immune complex glomerulonephritis. CASE PRESENTATION: We report the case of a 58-year-old Sri Lankan man who presented with gross hematuria. Further investigation revealed bicytopenia with splenomegaly and elevated serum creatinine. He had a renal biopsy, which revealed acute immune complex glomerulonephritis with interstitial inflammation. Results from an initial bone marrow biopsy and blood imaging were inconclusive. Three months later his renal function had deteriorated and a lymph node biopsy revealed mantle cell lymphoma. Within three months of initiating chemotherapy, his renal function returned to normal levels and remained normal at one year of follow-up. CONCLUSIONS: It is important to have a high degree of suspicion when patients present with acute immune complex glomerulonephritis with no other identifiable cause, because it could be the first presentation of a non-Hodgkin lymphoma such as mantle cell lymphoma.

Primary antiphospholipid syndrome presenting as antiphospholipid syndrome nephropathy: a case report.

INTRODUCTION: Primary antiphospholipid syndrome can be a difficult diagnosis in the absence of typical clinical features. We describe an unusual presentation of primary antiphospholipid syndrome mimicking vasculitis for which the only diagnostic clue on initial presentation was antiphospholipid syndrome nephropathy. CASE PRESENTATION: A 29-year-old Sri Lankan woman presented with features mimicking vasculitis with no obvious clinical features of antiphospholipid syndrome. Classical symptoms of antiphospholipid syndrome only appeared months later. A retrospective analysis showed that the only evidence of antiphospholipid syndrome at her first presentation was antiphospholipid syndrome nephropathy on her renal biopsy. CONCLUSIONS: A high degree of suspicion of antiphospholipid syndrome is needed when patients present with non-specific vasculitis features. It has a broad clinical impact as antiphospholipid syndrome can present to any clinician with rare manifestations such as nephropathy. This significantly adds to the advancement of knowledge as antiphospholipid syndrome nephropathy should be recognized as a true entity and considered as a classification criteria for antiphospholipid syndrome.

Long term outcome of acute kidney injury due to leptospirosis? A longitudinal study in Sri Lanka.

BACKGROUND: Leptospirosis is an important zoonotic disease of variable severity and is a common cause of acute kidney injury (AKI) in tropics. However the knowledge on long term renal outcome in leptospirosis is scarce. This study aims to assess the long-term renal outcome of AKI caused by leptospirosis. FINDINGS: Hospital records of patients who had developed AKI following leptospirosis (Serologically confirmed) presented to two Teaching Hospitals in Kandy district over 3 years from 2007 were studied. A total of 44 patients were included and they had been followed up at least for one year in out patient clinics with regular assessment including renal status. Renal histology was studied in two patients. The primary outcome measure was normalization of renal function at one year. Of the 44 patients, 31 were in the risk and injury stage (Group 1), and the rest of them were in the failure stage (Group 2) under RIFLE criteria. Of group 2 patients, 11 had abnormal renal functions on discharge. Their mean serum creatinine and GFR values on discharge were 392 mmol/l and 20 ml/min/1.73 m2. Other two patients had full renal recovery whilst in the hospital. Nine in the group 2 required renal replacement therapy by means of peritoneal dialysis, intermittent haemodialysis or haemofiltration. Seventeen out of the total had persistently abnormal renal functions on discharge. Of them 13 recovered their renal functions to normal. Four patients (9%) who belonged to group 2, had persistently abnormal renal functions after first year compatible with stage 3 chronic kidney disease (CKD). Renal histology of two patients showed tubulointerstitial lymphocyte infiltrate, tubular atrophy and interstitial fibrosis. CONCLUSION: The long term renal outcome of AKI following leptospirosis is satisfactory as only 9% of patients had abnormal renal functions compatible with early stage of CKD. Even among them, advanced CKD or dialysis dependency had not been observed.

Thrombotic microangiopathy and acute kidney injury in hump-nosed viper (Hypnale species) envenoming: a descriptive study in Sri Lanka.

Hump-nosed viper (Hypnale species) bites are common in Sri Lanka and a proportion of these bites lead to coagulation abnormalities and acute kidney injury (AKI). We observed thrombotic microangiopathy (TMA) among some of these patients, but its contribution to severity of AKI and other morbidities remains unknown. Thus, we report a case series of TMA following hump-nosed viper bite addressing the complications and renal out comes in Sri Lanka. This was a prospective observational study carried out at the nephrology unit, Kandy in Sri Lanka from October 2010 to October 2011 and included 11 patients with AKI following hump-nosed viper bites. All eleven cases needed renal replacement therapy (RRT) with intermittent haemodialysis for a period of 1-5 weeks. Of them, 7 patients developed TMA with evidence of microangiopathic haemolytic anaemia (MAHA), thrombocytopenia and severe anaemia needing multiple blood transfusions. They needed longer duration of RRT (range 2-5 weeks); 2 patients developed chronic kidney disease and two died during acute stage. Autopsy study found thrombosis of micro-vessels. Thrombotic microangiopathy could be a causative pathology of AKI in hump-nosed viper bite carrying poor outcome.

Coagulopthy, acute kidney injury and death following Hypnale zara envenoming: the first case report from Sri Lanka.

Snakebite is a major medical problem in developing Asia. Hump-nosed pit viper (Genus Hypnale) causes the most number of snakebites with significant morbidity and mortality in Sri Lanka. Even though there are three species (Hypnale hypnale, Hypnale zara and Hypnale nepa) in Sri Lanka there are few published literature on species-specific clinico-epidemiological data. This report describes an authenticated fatal case of a 47 years old male due to coagulopthy and acute kidney injury following envenoming by H. zara in Sri Lanka.