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Author |
Vervaet, B.A.; Nast, C.C.; Jayasumana, C.; Schreurs, G.; Roels, F.; Herath, C.; Kojc, N.; Samaee, V.; Rodrigo, S.; Gowrishankar, S.; Mousson, C.; Dassanayake, R.; Orantes, C.M.; Vuiblet, V.; Rigothier, C.; d' Haese, P.C.; de Broe, M.E. |
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Title |
Chronic interstitial nephritis in agricultural communities is a toxin induced proximal tubular nephropathy |
Type |
A1 Journal article |
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Year  |
2019 |
Publication |
Kidney international |
Abbreviated Journal |
Kidney Int |
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Volume |
97 |
Issue |
97 |
Pages |
350-369 |
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Keywords |
A1 Journal article; Electron microscopy for materials research (EMAT); Laboratory Experimental Medicine and Pediatrics (LEMP); Pathophysiology |
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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. |
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Wos |
000508449300020 |
Publication Date |
2019-11-23 |
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Abbreviated Series Title |
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Series Volume |
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Series Issue |
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Edition |
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ISSN |
0085-2538; 1523-1755 |
ISBN |
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Additional Links |
UA library record; WoS full record; WoS citing articles |
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Impact Factor |
8.395 |
Times cited |
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Open Access |
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Notes |
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Approved |
Most recent IF: 8.395 |
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Call Number |
UA @ admin @ c:irua:164305c:irua:166544 |
Serial |
5384 |
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Author |
Bervoets, A.R.J.; Behets, G.J.; Schryvers, D.; Roels, F.; Yang, Z.; Verberckmoes, S.C.; Damment, S.J.P.; Dauwe, S.; Mubiana, V.K.; Blust, R.; de Broe, M.E.; d' Haese, P.C. |
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Title |
Hepatocellular transport and gastrointestinal absorption of lanthanum in chronic renal failure |
Type |
A1 Journal article |
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Year |
2009 |
Publication |
Kidney international |
Abbreviated Journal |
Kidney Int |
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Volume |
75 |
Issue |
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Pages |
389-398 |
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Keywords |
A1 Journal article; Electron microscopy for materials research (EMAT); Pathophysiology |
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Abstract |
Lanthanum carbonate is a new phosphate binder that is poorly absorbed from the gastrointestinal tract and eliminated largely by the liver. After oral treatment, we and others had noticed 23 fold higher lanthanum levels in the livers of rats with chronic renal failure compared to rats with normal renal function. Here we studied the kinetics and tissue distribution, absorption, and subcellular localization of lanthanum in the liver using transmission electron microscopy, electron energy loss spectrometry, and X-ray fluoresence. We found that in the liver lanthanum was located in lysosomes and in the biliary canal but not in any other cellular organelles. This suggests that lanthanum is transported and eliminated by the liver via a transcellular, endosomal-lysosomal-biliary canicular transport route. Feeding rats with chronic renal failure orally with lanthanum resulted in a doubling of the liver levels compared to rats with normal renal function, but the serum levels were similar in both animal groups. These levels plateaued after 6 weeks at a concentration below 3 g/g in both groups. When lanthanum was administered intravenously, thereby bypassing the gastrointestinal tract-portal vein pathway, no difference in liver levels was found between rats with and without renal failure. This suggests that there is an increased gastrointestinal permeability or absorption of oral lanthanum in uremia. Lanthanum levels in the brain and heart fluctuated near its detection limit with long-term treatment (20 weeks) having no effect on organ weight, liver enzyme activities, or liver histology. We suggest that the kinetics of lanthanum in the liver are consistent with a transcellular transport pathway, with higher levels in the liver of uremic rats due to higher intestinal absorption. |
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Place of Publication |
New York, N.Y. |
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Wos |
000263145800009 |
Publication Date |
2008-12-03 |
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Series Editor |
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Series Title |
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Abbreviated Series Title |
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Series Volume |
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Series Issue |
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Edition |
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ISSN |
0085-2538;1523-1755; |
ISBN |
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Additional Links |
UA library record; WoS full record; WoS citing articles |
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Impact Factor |
8.395 |
Times cited |
29 |
Open Access |
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Notes |
Fwo; Iwt |
Approved |
Most recent IF: 8.395; 2009 IF: 6.193 |
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Call Number |
UA @ lucian @ c:irua:72290 |
Serial |
1417 |
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Author |
Yang, Z.; Schryvers, D.; Roels, F.; d' Haese, P.C.; de Broe, M.E. |
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Title |
Demonstration of lanthanum in liver cells by energy-dispersive X-ray spectroscopy, electron energy loss spectroscopy and high-resolution transmission electron microscopy |
Type |
A1 Journal article |
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Year |
2006 |
Publication |
Journal of microscopy |
Abbreviated Journal |
J Microsc-Oxford |
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Volume |
223 |
Issue |
2 |
Pages |
133-139 |
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Keywords |
A1 Journal article; Electron microscopy for materials research (EMAT); Pathophysiology |
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Abstract |
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Corporate Author |
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Publisher |
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Place of Publication |
Oxford |
Editor |
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Language |
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Wos |
000239702700006 |
Publication Date |
2006-08-10 |
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Series Editor |
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Series Title |
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Abbreviated Series Title |
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Series Volume |
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Series Issue |
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Edition |
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ISSN |
0022-2720;1365-2818; |
ISBN |
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Additional Links |
UA library record; WoS full record; WoS citing articles |
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Impact Factor |
1.692 |
Times cited |
29 |
Open Access |
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Notes |
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Approved |
Most recent IF: 1.692; 2006 IF: 1.947 |
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Call Number |
UA @ lucian @ c:irua:59109 |
Serial |
633 |
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