Early Ultrastructural Changes in Biopsies From Patients With Symptomatic CKD of Uncertain Etiology.

Introduction: Although the investigation of chronic kidney disease of uncertain etiology (CKDu) has identified many possible influencing factors in recent years, the exact pathomechanism of this disease remains unclear. Methods: In this study, we collected 13 renal biopsies from patients with symptomatic CKDu (Sym-CKDu) from Sri Lanka with well-documented clinical and socioeconomic factors. We performed light microscopy and electron microscopic evaluation for ultrastructural analysis, which was compared with 100 biopsies from German patients with 20 different kidney diseases. Results: Of the 13 Sri Lankan patients, 12 were men (92.3%), frequently employed in agriculture (50%), and experienced symptoms such as feeling feverish (83.3%), dysuria (83.3%), and arthralgia (66.6%). Light microscopic evaluation using activity and chronicity score revealed that cases represented early stages of CKDu except for 2 biopsies, which showed additional signs of diabetes. Most glomeruli showed only mild changes, such as podocyte foot process effacement on electron microscopy. We found a spectrum of early tubulointerstitial changes including partial loss of brush border in proximal tubules, detachment of tubular cells, enlarged vacuoles, and mitochondrial swelling associated with loss of cristae and dysmorphic lysosomes with electron-dense aggregates. None of these changes occurred exclusively in Sym-CKDu; however, they were significantly more frequent in these cases than in the control cohort. Conclusion: In conclusion, our findings confirm the predominant and early alterations of tubular structure in CKDu that can occur without significant glomerular changes. The ultrastructural changes do not provide concrete evidence of the cause of CKDu but were significantly more frequent in Sym-CKDu than in the controls.

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.

Could Consumption of Trace Element-Contaminated Rice Be a Risk Factor for Acute Interstitial Nephritis with Uncertain Etiology in the Dry Zone of Sri Lanka?

Ingestion of toxic trace elements in the human body has been considered one of the major reasons for renal dysfunction. Chronic kidney disease with uncertain etiological factors (CKDu) is a recently described clinical entity in which the disease is found in geographically isolated pockets in the dry zone of Sri Lanka. In CKDu regions, an increasing number of cases are reported with acute interstitial nephritis without any known reason (AINu). However, recent exposure to certain risk behaviors or nephrotoxins, or both, is suspected for the AINu. Consumption of foods that are contaminated with trace elements is one of the main pathways of human exposure to environmental toxins. The current study was carried out to assess the possibility of trace element-contaminated rice consumption on the etiopathogenesis of AINu. Samples of rice consumed by 32 clinically diagnosed AINu cases were collected and analyzed for possible nephrotoxic trace elements. Out of 32 patients, 26 were histologically confirmed with tubulointerstitial disease. The results revealed that the mean values of Cd, As, and Pb were 0.18, 0.055, and 0.135 mg/kg, with ranges of 0.020-1.06, 0.012-0.222, and 0.003-0.744 mg/kg (on dry weight basis), respectively. This study indicated that the investigated toxic trace element levels of rice consumed by AINu were reasonably below the recommended levels of the Codex Alimentarius Commission of FAO and WHO. Hence, it is less likely that rice consumption is to be a risk factor for the etiology of AINu.

Effectiveness of Low-dose Ethinylestradiol/Cyproterone Acetate and Ethinylestradiol/Desogestrel with and without Metformin on Hirsutism in Polycystic Ovary Syndrome: A Randomized, Double-blind, Triple-dummy Study.

BACKGROUND: The effectiveness of different combined oral contraceptive pills and metformin in reducing hirsutism in patients with polycystic ovary syndrome (PCOS) remains unclear. OBJECTIVE: We sought to determine the effects of ethinylestradiol (35µg)/cyproterone acetate (2mg) (EE/CPA) and ethinylestradiol (20µg)/desogestrel (0.15mg) (EE/DES), alone or with metformin, on hirsutism in PCOS. METHODS: A randomized, double-blind, triple-dummy study was conducted on women with PCOS and hirsutism (N=107) who received one of four drug combinations (Arm A: EE/CPA; Arm B: EE/DES; Arm C: EE/CPA plus metformin; or Arm D: EE/DES plus metformin). Hirsutism was assessed at baseline, six months, and 12 months by using five outcomes variables. RESULTS: No outcomes variable showed a significant difference between the four arms at 12 months. There was a significant reduction in both hair density and modified Ferriman-Gallwey score (mFGS) in Arm A, mFGS in Arm B, hair density in Arm C, and diameter of sideburn hair in Arm D, respectively. Separately, there was a significant increase noted in the hair growth rate of chin and an improvement in patients' perceptions of hirsutism in all four study arms. CONCLUSION: EE/CPA and EE/DES were equally effective in improving hirsutism in PCOS, with no added benefit from low-dose metformin. Sri Lanka Clinical Trials Registry (http://www.slctr.lk) registration no. SLCTR/2015/007.

Sequel and therapeutic modalities of leptospirosis associated severe pulmonary haemorrhagic syndrome (SPHS); a Sri Lankan experience.

BACKGROUND: The emergence of leptospirosis-associated severe pulmonary hemorrhagic syndrome (SPHS) with high case fatality has been reported from many countries. Understanding of clinical disease and sequel of SPHS needs larger studies with adequate numbers. The purpose of this study was to describe the characteristics and sequel by different therapeutic approaches for SPHS in Leptospirosis in Sri Lanka. METHODS: This study was conducted at Teaching Hospital-Karapitiya (THK), Galle, Sri Lanka from June 2015 to December 2017. THK is the main tertiary care center for the Southern Province. All confirmed-cases of leptospirosis who presented during this period and were admitted to five medical units of THK were included in this study. SPHS was defined as a patient presenting; haemoptysis, arterial hypoxemia (Acute Lung Injury Score < 2.5), haemoglobin drop (10% from the previous value), or diffused alveolar shadows in the chest radiograph, without alternative explanation other than leptospirosis. RESULTS: Of the 128 MAT confirmed cases of leptospirosis, 111 (86.7%) had acute kidney injury (AKI) whilst SPHS was seen in 80 (62.5%). Patients typically developed SPHS within the first week of illness, mostly on days 4 and 5. The case fatality rate of this study sample was 28.1% (n = 36), while for patients with SPHS, it was 41.5%. Most of the deaths (n = 19) were within the first 3 days of admission (on the same day 8, and within next 48 h 11). Among SPHS patients, 59 received therapeutic plasma exchange (TPE). The survival rate was higher (n = 35, 74.5%) when the TPE was performed within the first 48 h of detecting SPHS compared to patients in whom the procedure was done after 48 h (n = 5, 54.5%). Of the 19 leptosprosis patients with SPHS who did not receive TPE, 17 died (89.5%). However, the group of patients who received TPE was primarily the patients survived beyond day 3. CONCLUSIONS: We observed that during the study period, SPHS was common and the mortality rate was higher in the study area. The treatment modalities tested need further evaluation and confirmation.

Diagnostic accuracy of ultrasound characteristics in the identification of malignant thyroid nodules.

OBJECTIVE: This study was aimed at determining the diagnostic accuracy of the ultrasound characteristics in the identification of malignant thyroid nodules in patients attending the surgical clinic at a tertiary care hospital in Sri Lanka. RESULTS: This prospective validation study was conducted among 263 patients attending the surgical clinic at a tertiary care hospital, Sri Lanka. The ultrasound characteristics having statistically significant associations with thyroid malignancies were identified by employing a multivariable analysis. These ultrasound characteristics were compared with Fine Needle Aspiration Cytology results and indicators of diagnostic accuracy were computed. The study sample consisted of 33 malignant and 230 benign nodules. Internal vascularity, hypoechogenicity and microcalcification showed statistically significant positive associations with thyroid malignancy (p < 0.05). The highest positive likelihood ratio was observed for the presence of microcalcifications (10.4, 95% CI 4.6-23.7) with a specificity of 96.5% (95% CI 93.3-98.5%). Hypoechogenicity had a sensitivity of 66.7% (95% CI 48.2-82.0%) and a specificity of 74.8% (95% CI 68.6-80.3%). The presence of at least one positive ultrasound characteristic yielded the highest sensitivity (87.9%, 95% CI 71.8-96.6%), whereas, the presence of all three characteristics yielded a near perfect specificity (99.6%, 95% CI 97.6-99.9%). Hence, the presence of microcalcifications was found to be the single most useful criterion in predicting thyroid malignancy.

Prospective Biopsy-Based Study of CKD of Unknown Etiology in Sri Lanka.

BACKGROUND AND OBJECTIVES: A kidney disease of unknown cause is common in Sri Lanka's lowland (dry) region. Detailed clinical characterizations of patients with biopsy-proven disease are limited, and there is no current consensus on criteria for a noninvasive diagnosis. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: We designed a prospective study in a major Sri Lankan hospital servicing endemic areas to ascertain pathologic and clinical characteristics of and assess risk factors for primary tubulointerstitial kidney disease. We used logistic regression to determine whether common clinical characteristics could be used to predict the presence of primary tubulointerstitial kidney disease on kidney biopsy. RESULTS: From 600 new patients presenting to a tertiary nephrology clinic over the course of 1 year, 87 underwent kidney biopsy, and 43 (49%) had a biopsy diagnosis of primary tubulointerstitial kidney disease. On detailed biopsy review, 13 (30%) had evidence of moderate to severe active kidney disease, and six (15%) had evidence of moderate to severe chronic tubulointerstitial kidney disease. Patients with tubulointerstitial kidney disease were exclusively born in endemic provinces; 91% spent a majority of their lifespan there. They were more likely men and farmers (risk ratio, 2.0; 95% confidence interval, 1.2 to 2.9), and they were more likely to have used tobacco (risk ratio, 1.7; 95% confidence interval, 1.0 to 2.3) and well water (risk ratio, 1.5; 95% confidence interval, 1.1 to 2.0). Three clinical characteristics-age, urine dipstick for protein, and serum albumin-could predict likelihood of tubulointerstitial kidney disease on biopsy (model sensitivity of 79% and specificity of 84%). Patients referred for kidney biopsy despite comorbid diabetes or hypertension did not experience lower odds of tubulointerstitial kidney disease. CONCLUSIONS: A primary tubulointerstitial kidney disease occurs commonly in specific regions of Sri Lanka with characteristic environmental and lifestyle exposures.

Association between visceral adiposity index, hirsutism and cardiometabolic risk factors in women with polycystic ovarian syndrome: A cross-sectional study

Introduction: Visceral adiposity index (VAI) is a mathematical index derived from the body mass index (BMI), waist circumference (WC), serum fasting triglyceride (TG) and high-density lipoprotein cholesterol (HDL-C). It reflects visceral adipocyte dysfunction (VAD) and is associated with cardiometabolic risk. Women with polycystic ovarian syndrome (PCOS) have adipocyte dysfunction, which is associated with metabolic disorders. Hirsutism in PCOS is considered to be due to high insulin levels which enhances androgen activity at the pilosebaceous unit. Objectives: To determine the association between VAI, hirsutism and cardiometabolic risk factors in patients with PCOS. Methods: A total of 99 patients aged 18-40 years with PCOS diagnosed by the Rotterdam consensus criteria-2003 and a hirsutism score of 8 or more according to the Ferriman-Gallway Score (FGS) were studied. BMI, WC, fasting lipid profile, serum leptin, insulin, sex hormone binding globulin (SHBG), free-androgen index (FAI), fasting blood glucose (FBG) and oral glucose tolerance test (OGTT) were determined. Homeostasis model assessment (HOMA)-beta, HOMA-insulin resistance (IR) and VAI were calculated. Diameter and rate of hair growth at sideburns and chin; density of hair at sideburns were measured. Data were analyzed by SPSS-22.0. Results: There was no significant association between parameters of hirsutism and VAI. There was a significant association between VAI and OGTT, FAI, systolic and diastolic blood pressure: but not between VAI and other metabolic parameters. Conclusion: Visceral adipocyte dysfunction is closely linked to glucose intolerance and blood pressure in women with PCOS. However, hirsutism is unlikely to be due to adipocyte dysfunction.

Infective myositis, an uncommon presentation of melioidosis: a case report and review of the literature.

BACKGROUND: Melioidosis is considered endemic in certain areas of the world. Musculoskeletal and soft tissue involvement are relatively uncommon presentations in melioidosis. We present a case of infective myositis in a patient with melioidosis in Sri Lanka, which is not considered an endemic country. Even though multiple cases of melioidosis have been reported with an increasing number in Sri Lanka, infective myositis secondary to melioidosis was not reported previously. CASE PRESENTATION: A 60-year-old Sinhalese man with diabetes presented with fever of 4 months' duration and a limp with a painful lump on the right side of the upper thigh of 2 months' duration. He had been treated in a local hospital for community-acquired pneumonia 3 weeks prior to this admission, for which he had received intravenous meropenem and teicoplanin with intensive care unit admission. He had a 0.5-cm × 0.5-cm tender lump over the right vastus lateralis muscle, and contrast-enhanced computed tomography of the area showed an ill-defined, heterogeneously enhancing, hypodense area involving the vastus lateralis, vastus intermedius, and quadratus femoris, suggestive of infective myositis but without abscess formation. Histopathology of the muscle biopsied from the vastus lateralis showed suppurative inflammation of subcutaneous fat with connective tissue necrosis and muscle infiltrated by lymphocytes. These features are suggestive of infective myositis possibly due to melioidosis. Although the result of a culture taken from the muscle biopsy was negative, the patient's antibody titer was strongly positive for melioidosis. He did not show any other areas with infected foci. He was treated with intravenous meropenem for 2 weeks and responded well. He was discharged with trimethoprim-sulfamethoxazole for 6 months as a maintenance therapy. CONCLUSION: Melioidosis is commonly an undiagnosed disease that has a wide variety of clinical presentations. Myositis in melioidosis is uncommon, and careful evaluation is mandatory to avoid misdiagnosis of this treatable but fatal disease. The clinician should have a high index of clinical suspicion, and further clinical and epidemiological studies are needed to determine the true burden of the disease.

Screening for chronic kidney disease of uncertain aetiology in Sri Lanka: usability of surrogate biomarkers over dipstick proteinuria.

BACKGROUND: The use of dipstick proteinuria to screen Chronic Kidney Disease of uncertain aetiology (CKDu) in Sri Lanka is a recently debated matter of dispute. The aim of this study was to assess the suitability of biomarkers: serum creatinine, cystatin C and urine albumin to creatinine ratio (ACR) for screening CKDu in Sri Lanka. METHODS: Forty-four male CKDu patients and 49 healthy males from a CKDu-endemic region were selected. Meanwhile, 25 healthy males from a non-endemic region were selected as an absolute control. The diagnostic accuracy of each marker was compared using the above three study groups. RESULTS: In receiver operating characteristics (ROC) plots for creatinine, cystatin C and ACR, values of area under the curve (AUC) were 0.926, 0.920 and 0.737 respectively when CKDu was compared to non-endemic control. When CKDu was compared to endemic control, AUCs of above three analytes were distinctly lower as 0.718, 0.808 and 0.678 respectively. Cystatin C exhibited the highest sensitivity for CKDu when analyzed against both control groups where respective sensitivities were 0.75 against endemic control and 0.89 against non-endemic control. ROC-optimal cutoff limits of creatinine, cystatin C and ACR in CKDu vs non-endemic control were 89.0 µmol/L, 1.01 mg/L and 6.06 mg/g-Cr respectively, whereas in CKDu vs endemic control the respective values were 111.5 µmol/L, 1.22 mg/L and 12.66 mg/g-Cr. CONCLUSIONS: Amongst the three biomarkers evaluated in this study, our data suggest that Cystatin C is the most accurate functional marker in detecting CKDu in endemic regions, yet the high cost hinders its usability on general population. Creatinine is favorable over dipstick proteinuria owing to its apparent accuracy and cost efficiency, while having the ability to complement the kidney damage marker (ACR) in screening. ACR may not be favorable as a standalone screening marker in place of dipstick proteinuria due to its significant decline in sensitivity against the CKDu-endemic population. However, creatinine and ACR in a complementary manner could overcome current shortcomings of dipstick proteinuria and such a dual marker tool could be commodious in screening CKDu-type tubulointerstital diseases. Furthermore, use of ACR may also increase the ability to clinically discriminate CKDu from other glomerular nephropathies.

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).

Whole-exome sequencing reveals genetic variants associated with chronic kidney disease characterized by tubulointerstitial damages in North Central Region, Sri Lanka.

OBJECTIVES: The familial clustering observed in chronic kidney disease of uncertain etiology (CKDu) characterized by tubulointerstitial damages in the North Central Region of Sri Lanka strongly suggests the involvement of genetic factors in its pathogenesis. The objective of the present study is to use whole-exome sequencing to identify the genetic variants associated with CKDu. METHODS: Whole-exome sequencing of eight CKDu cases and eight controls was performed, followed by direct sequencing of candidate loci in 301 CKDu cases and 276 controls. RESULTS: Association study revealed rs34970857 (c.658G > A/p.V220M) located in the KCNA10 gene encoding a voltage-gated K channel as the most promising SNP with the highest odds ratio of 1.74. Four rare variants were identified in gene encoding Laminin beta2 (LAMB2) which is known to cause congenital nephrotic syndrome. Three out of four variants in LAMB2 were novel variants found exclusively in cases. CONCLUSION: Genetic investigations provide strong evidence on the presence of genetic susceptibility for CKDu. Possibility of presence of several rare variants associated with CKDu in this population is also suggested.

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.

An integrative study of the genetic, social and environmental determinants of chronic kidney disease characterized by tubulointerstitial damages in the North Central Region of Sri Lanka.

OBJECTIVES: Previous investigations on chronic kidney disease of unknown etiology characterized by tubulointerstitial damages (CKDu) in the North Central Region (NCR) of Sri Lanka have supported the involvement of social, environmental and genetic factors in its pathogenesis. METHODS: We conducted a social-environmental-and-genetic epidemiology study on a male population in NCR to investigate the genetic and environmental contributors. We recruited 311 case-series patients and 504 control candidates. Of the 504 control candidates, 218 (43%) were eliminated because of the presence of hypertension, proteinuria, high HbA1c, high serum creatinine or high alpha-1 microglobulin in urine. RESULTS AND DISCUSSION: None of 18 metals measured (µg//) in urine, including Cd, As and Pb, showed significantly higher concentrations in cases compared with controls. As speciation results showed that 75-80% of total urinary As was in the form of arsenobetaine, which is non-toxic to humans. None of the metal concentrations in drinking water samples exceeded guideline values. A genome-wide association study (GWAS) was conducted to determine the genetic contributors. The GWAS yielded a genome-wide significant association with CKDu for a single nucleotide polymorphism (SNP; rs6066043; p=5.23 × 10(-9) in quantitative trait locus analysis; p=3.73 × 10(-9) in dichotomous analysis) in SLC13A3 (sodium-dependent dicarboxylate transporter member 3). The population attributable fraction and odds ratio for this SNP were 50% and 2.13. Genetic susceptibility was identified as the major risk factor for CKDu. However, 43% of the apparently healthy male population suffers from non-communicable diseases, suggesting their possible influence on CKDu progression.

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.

Tubulointerstitial damage as the major pathological lesion in endemic chronic kidney disease among farmers in North Central Province of Sri Lanka.

Chronic kidney disease of uncertain etiology (CKDu) in North Central Province of Sri Lanka has become a key public health concern in the agricultural sector due to the dramatic rise in its prevalence and mortality among young farmers. Although cadmium has been suspected as a causative pathogen, there have been controversies. To date, the pathological characteristics of the disease have not been reported. Histopathological observations of 64 renal biopsies obtained at Anuradhapura General Hospital from October 2008 to July 2009 were scored according to Banff 97 Working Classification of Renal Allograft pathology. The correlations between the histological observations and clinical parameters were statistically analyzed. Interstitial fibrosis and tubular atrophy with or without nonspecific interstitial mononuclear cell infiltration was the dominant histopathological observation. Glomerular sclerosis, glomerular collapse, and features of vascular pathology such as fibrous intimal thickening and arteriolar hyalinosis were also common. Although hypertension was identified as one of the common clinical features among the cases, it did not influence the histopathological lesions in all the cases. This study concludes that tubulointerstitial damage is the major pathological lesion in CKDu. Exposure(s) to an environmental pathogen(s) should be systematically investigated to elucidate such tubulointerstitial damage in CKDu.