Assessment of Risk of Exposure to Leishmania Parasites among Renal Disease Patients from a Renal Unit in a Sri Lankan Endemic Leishmaniasis Focus.

Leishmania donovani causes both cutaneous and visceral leishmaniasis (CL and VL) in Sri Lanka, where chronic kidney disease (CKD) and kidney transplant recipients' (KTR) geographical areas overlap. This study aimed to determine the risk of exposure to Leishmania infection among renal patients. This cross-sectional study in a renal unit assessed clinical symptoms and signs of CL and VL in recipients of blood/kidney or immunosuppressives. Sera were tested with Leishmania-specific DAT and rK-39 ELISA. There were 170 participants. A total of 84.1% (n = 143) were males (CKD: 101, KTR; 42, mean age 45) and 27 were females (females: CKD: 23, KTR: 4, mean age 39 years). Recipients of blood transfusion/s within last 2 years: 75.9% (CKD: 115, KTR: 14), on immunosuppressive therapy: 34.1% (CKD: 13, KTR: 45). Two CKD patients repeatedly showed clear positive titres (1: 12,800 and 1: 3200) with Leishmania-DAT and another two (CKD) became marginally positive with rK39-ELISA. Prevalence of anti-Leishmania antibodies: 2.4% (4/170). All four patients were clinically asymptomatic and were recipients of recent blood transfusions. Attributable risk of exposure to Leishmania infection through blood transfusions was 0.032, OR 2.99 (95% CI = 0.16 to 56.45, p = 0.47). Therefore, routine screening of kidney/blood donors and CKD and KTR patients in Sri Lanka may not be necessary.

Chronic interstitial nephritis in agricultural communities is a toxin-induced proximal tubular nephropathy.

Almost 30 years after the detection of chronic interstitial nephritis in agricultural communities (CINAC) its etiology remains unknown. To help define this we examined 34 renal biopsies from Sri Lanka, El Salvador, India and France of patients with chronic kidney disease 2-3 and diagnosed with CINAC by light and electron microscopy. In addition to known histopathology, we identified a unique constellation of proximal tubular cell findings including large dysmorphic lysosomes with a light-medium electron-dense matrix containing dispersed dark electron-dense non-membrane bound "aggregates". These aggregates associated with varying degrees of cellular/tubular atrophy, apparent cell fragment shedding and no-weak proximal tubular cell proliferative capacity. Identical lysosomal lesions, identifiable by electron microscopy, were observed in 9% of renal transplant implantation biopsies, but were more prevalent in six month (50%) and 12 month (67%) protocol biopsies and in indication biopsies (76%) of calcineurin inhibitor treated transplant patients. The phenotype was also found associated with nephrotoxic drugs (lomustine, clomiphene, lithium, cocaine) and in some patients with light chain tubulopathy, all conditions that can be directly or indirectly linked to calcineurin pathway inhibition or modulation. One hundred biopsies of normal kidneys, drug/toxin induced nephropathies, and overt proteinuric patients of different etiologies to some extent could demonstrate the light microscopic proximal tubular cell changes, but rarely the electron microscopic lysosomal features. Rats treated with the calcineurin inhibitor cyclosporine for four weeks developed similar proximal tubular cell lysosomal alterations, which were absent in a dehydration group. Overall, the finding of an identical proximal tubular cell (lysosomal) lesion in CINAC and calcineurin inhibitor nephrotoxicity in different geographic regions suggests a common paradigm where CINAC patients undergo a tubulotoxic mechanism similar to calcineurin inhibitor nephrotoxicity.

Normality data of eGFR and validity of commonly used screening tests for CKD in an area with endemic CKD of unknown etiology; need for age and sex based precise cutoff values.

BACKGROUND: Chronic Kidney Disease in certain part of Sri Lanka and increasing burden of CKD in some other countries is a global public health problem. While the underlying causes of majority of cases are unknown, effective control and prevention strategies are yet to be taken. Though the disease has been identify more than decade ago, baseline data on renal function are not available. This study reports the age and sex disaggregated data of renal functions among screening participants of the Anuradhapura, the district with the highest disease burden in Sri Lanka. METHODS: The screening prorgramme was done as a part of CKD control programme of Anuradhapura. All screening centers were visited and information and urine sample collection tubes were distributed before the screening date. A serum and urine sample was taken from all participants. In a subsample, urine sulfosalicylic acid test (SSA Test), urine dipstick test, urine albumin to creatinine ratio (UACR) and urine protein to creatinine ratio (UPCR) was done. RESULTS: The study sample included 7768 apparently healthy people aging 18 to 93 years and females (n = 5522) accounted for 71.1% of the sample. Mean age of the participants was 45.9 (SD 14.1) years. Mean eGFR in this population was 90.8 mL/min/1.73m2(SD 24.6) with a significantly lower eGFR (88.1 mL/min/1.73m2) among males compared to female (92.8 mL/min/1.73m2). Mean eGFR was 115 mL/min/1.73m2 (SE .5) among participants aging less than 30 and this value drastically reduced to 59.1 mL/min/1.73m2 (SE 1.2) among people aging more than 70 years. Proportion of people having reduction of eGFR compatible with mild, moderate, severe and kidney failure categories was 33.9(32.7-34.8), 8.4(7.8-9.0), 1.5(1.2-1.7) and 0.7(0.5-0.9). The age and sex adjusted prevalence of eGFR less than 60 mL/min/1.73 m2 in a single sample in this population was 10.6%. Bayesian Latent Class model analysis shows that UPCR> 150 has the highest sensitivity to detect those who are with eGFR less than 60 mL/min/1.73 m2. UACR, the usual recommended test as a screening test was having a sensitivity of 35.3% in this population. CONCLUSION: UPCR and UACR should be use as a screening tests in areas with high proportion of CKDu patients. More research are required to investigate the use of age and sex specific cut off values to diagnose CKD.

Morphological and clinical findings in Sri Lankan patients with chronic kidney disease of unknown cause (CKDu): Similarities and differences with Mesoamerican Nephropathy.

In Sri Lanka, an endemic of chronic kidney disease of unknown origin (CKDu) is affecting rural communities. The endemic has similarities with Mesoamerican Nephropathy (MeN) in Central America, however it has not yet been clarified if the endemics are related diagnostic entities. We designed this study of kidney biopsies from patients with CKDu in Sri Lanka to compare with MeN morphology. Eleven patients with CKDu were recruited at the General Hospital, Polonnaruwa, using similar inclusion and exclusion criteria as our previous MeN studies. Inclusion criteria were 20-65 years of age and plasma creatinine 100-220 µmol/L. Exclusion criteria were diabetes mellitus, uncontrolled hypertension and albuminuria >1g/24h. Kidney biopsies, blood and urine samples were collected, and participants answered a questionnaire. Included participants were between 27-61 years of age and had a mean eGFR of 38±14 ml/min/1.73m2. Main findings in the biopsies were chronic glomerular and tubulointerstitial damage with glomerulosclerosis (8-75%), glomerular hypertrophy and mild to moderate tubulointerstitial changes. The morphology was more heterogeneous and interstitial inflammation and vascular changes were more common compared to our previous studies of MeN. In two patients the biopsies showed morphological signs of acute pyelonephritis but urine cultures were negative. Electrolyte disturbances with low levels of serum sodium, potassium, and/or magnesium were common. In the urine, only four patients displayed albuminuria, but many patients exhibited elevated α-1-microglobulin and magnesium levels. This is the first study reporting detailed biochemical and clinical data together with renal morphology, including electron microscopy, from Sri Lankan patients with CKDu. Our data show that there are many similarities in the biochemical and morphological profile of the CKDu endemics in Central America and Sri Lanka, supporting a common etiology. However, there are differences, such as a more mixed morphology, more interstitial inflammation and vascular changes in Sri Lankan patients.