Targeted urine microscopy in Anderson-Fabry disease: a cheap, sensitive and specific diagnostic technique.

BACKGROUND: Anderson-Fabry disease (AFD) is an X-linked lysosomal storage disorder resulting from the deficiency of trihexosylceramide α-galactosidase (α-Gal A). The diagnosis is often missed or delayed, and specific diagnostic tests (serum α-Gal A activity, genotyping or biopsy) are expensive and not widely available. We evaluated the diagnostic potential of urine microscopy in AFD. METHODS: We studied 35 male and female AFD patients across a wide phenotypic spectrum and 21 controls with other renal diseases. Fresh urine sediment was examined under phase-contrast microscopy using polarized light for Maltese cross (MC) particles, anti-CD77 antibody to detect globotriaosylceramide (GL3, the substrate of α-Gal A), and anti-podocalyxin antibody to assess podocyte excretion. RESULTS: Characteristic MC 2 particles and anti-CD77 binding within vacuolated urinary epithelial cells were both detected in AFD with high sensitivity and specificity (MC 2 detection sensitivity 100%, 95% confidence interval (CI) 85.4-100%, specificity 100%, CI 80.8-100%; anti-CD77-binding sensitivity 97.1%, CI 83.3-99.9, specificity 100%, CI 80.8-100%). Albuminuria (urinary albumin-to-creatinine ratio, ACR) correlated with quantitative particle excretion--in low, intermediate and high MC excretors, and median ACR was 1.6, 6.9 and 20.0 mg/µmol, respectively (analysis of variance P = 0.017). Podocyte staining was positive in ~50% of all AFD patients and was similar in those with and without clinical Fabry nephropathy (FN), whether or not treated with enzyme replacement. CONCLUSIONS: Targeted urinary microscopy is a non-invasive, inexpensive, accessible and rapid diagnostic technique, especially applicable where serum α-Gal A activity and genotyping are not affordable or available. As the number of urinary MC 2 particles increases with rising albuminuria, the technique may also be useful in assessing FN burden.

Chronic kidney disease of unknown etiology in Sri Lanka.

INTRODUCTION: In the last two decades, chronic kidney disease of unknown etiology (CKDu) has emerged as a significant contributor to the burden of chronic kidney disease (CKD) in rural Sri Lanka. It is characterized by the absence of identified causes for CKD. The prevalence of CKDu is 15.1-22.9% in some Sri Lankan districts, and previous research has found an association with farming occupations. METHODS: A systematic literature review in Pubmed, Embase, Scopus, and Lilacs databases identified 46 eligible peer-reviewed articles and one conference abstract. RESULTS: Geographical mapping indicates a relationship between CKDu and agricultural irrigation water sources. Health mapping studies, human biological studies, and environment-based studies have explored possible causative agents. Most studies focused on likely causative agents related to agricultural practices, geographical distribution based on the prevalence and incidence of CKDu, and contaminants identified in drinking water. Nonetheless, the link between agrochemicals or heavy metals and CKDu remains to be established. No definitive cause for CKDu has been identified. DISCUSSION: Evidence to date suggests that the disease is related to one or more environmental agents, however pinpointing a definite cause for CKDu is challenging. It is plausible that CKDu is multifactorial. No specific guidelines or recommendations exist for treatment of CKDu, and standard management protocols for CKD apply. Changes in agricultural practices, provision of safe drinking water, and occupational safety precautions are recommended by the World Health Organization.