Renal tubular lysosomal vacuoles are a generic toxic manifestation and not particularly associated with agrochemicals and heavy metal toxicity or specific to a disease

Abstract

I congratulate Vervaet et al. for their article containing excellent pictures of tubular cells. 1 Vervaet B.A. Nast C.C. Jayasumana C. et al. Chronic interstitial nephritis in agricultural communities is a toxin-induced proximal tubular nephropathy. Kidney Int. 2020; 97: 350-369 Abstract Full Text Full Text PDF PubMed Scopus (33) Google Scholar However, the acronym used, CINAC (chronic interstitial nephritis in agricultural communities), is misleading; persons not living in agricultural regions and not exposed to agriculture or agrochemicals can also develop the same chronic kidney disease of unknown etiology, which stigmatizes them. 2 Ileperuma O. Weeraratne S. Wimalawansa S.J. Acronyms, CINAC, ACN, KDUCAL or NUCAL and so on are inappropriate to use for describing CKDu. J Epidemiol Community Health. 2018; 72: 967-968 Crossref PubMed Scopus (3) Google Scholar Lysosomal organelles facilitate cellular metabolism, degradation of macromolecules, recycling, and redox regulation, which maintain cell survival. 3 Coutinho M.F. Alves S. From rare to common and back again: 60 years of lysosomal dysfunction. Mol Genet Metab. 2016; 117: 53-65 Crossref PubMed Scopus (15) Google Scholar Lysosome tubulopathy includes hereditary and acquired forms. Genetic abnormalities of lysosomal organelles cause life-threatening storage disorders, 3 Coutinho M.F. Alves S. From rare to common and back again: 60 years of lysosomal dysfunction. Mol Genet Metab. 2016; 117: 53-65 Crossref PubMed Scopus (15) Google Scholar whereas acquired lysosomopathies manifest as generic tubulointerstitial nephropathies. Chronic interstitial nephritis in agricultural communities is a toxin-induced proximal tubular nephropathyKidney InternationalVol. 97Issue 2PreviewAlmost 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”. Full-Text PDF Open AccessThe authors replyKidney InternationalVol. 97Issue 5PreviewWe thank Dr. Wimalawansa1 for the interest in our work2 and appreciate the critical remarks. Full-Text PDF Chronic interstitial nephritis of agricultural communities: continuing with the term CKDu (chronic kidney disease of unknown cause) is detrimentalKidney InternationalVol. 98Issue 3PreviewI read with interest the letter by Wimalawansa1 commenting on the article by Vervaet et al.2 and their response.3 Vervaet et al. reiterate that the main message of their article is the hard evidence of a toxic etiology to chronic interstitial nephritis of agricultural communities (CINAC)/chronic kidney disease of unknown cause (CKDu), although there has been no previous cellular evidence. Although Wimalawansa seems to concede that CINAC is likely a toxic nephropathy, his usage of the term “lysosomal vacuolation” clearly misinterprets the description of the CINAC lysosomal inclusions, which seem to be unique to some toxic nephropathies and not others. Full-Text PDF The pathologist’s viewKidney InternationalVol. 97Issue 5PreviewThe letter from Wimalawansa1 regarding the article by Vervaet et al.2 expresses the opinion that the findings reported in the latter article are “nonspecific and . . . too preliminary and overly theoretical to tie to agrochemicals” and are “speculative and not novel.” For certain, as Wimalawansa notes, lysosomal tubulopathies are not specific and may be caused by a wide variety of agents including but not limited to various drugs, solvents, and heavy metals. It is therefore not unreasonable to suggest that the results are too preliminary to tie the morphologic findings associated with chronic interstitial nephritis in agricultural communities/chronic kidney disease of unknown etiology to agrochemicals or any other specific causative factor, a limitation recognized by Vervaet et al. Full-Text PDF