Chronic interstitial nephritis in agricultural communities is a toxin-induced proximal tubular nephropathy
Year: 2019
Type: article
Study design: Observational Study
Abstract: 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.
Source: Kidney International
Authors: Benjamin A. Vervaet, Cynthia C. Nast, Channa Jayasumana, Gerd Schreurs, Frank Roels, Chula Herath, Nika Kojc, Vahid Samaee, Sonali Rodrigo, Swarnalata Gowrishankar, Christiane Mousson, Rajeewa Dassanayake, Carlos M. Orantes, Vincent Vuiblet, Claire Rigothier, Patrick C. D’Haese, Marc E. De Broe
Institutions: University of Antwerp, Cedars-Sinai Medical Center, Rajarata University of Sri Lanka, Ghent University, University of Ljubljana, Apollo Hospitals, Apollo Hospitals, CHU Dijon Bourgogne, Ministerio de Salud, Centre Hospitalier Universitaire de Reims, Centre Hospitalier Universitaire de Bordeaux
Language: English
Subfield: Nephrology
Field: Medicine
Domain: Health Sciences
Open Access status: hybrid
Estimated APC paid: $3,200
Awards: Toxin induced lysosomal storage disease: a new etiological, mechanistic, diagnostic and prognostic paradigm for the worldwide increasing prevalence of agrochemical-associated nephropathy, CINAC, a major globally emerging chronic renal disease of unknown origin: unraveling the molecular mechanism and etiology to allow diagnostic tool development.
OpenAlex ID: W2990659946