Abstract |
Nephropathic cystinosis is characterized clinically by generalized proximal renal tubular dysfunction, renal Fanconi Syndrome and progressive renal failure. Glomerular-proximal tubule disconnection has been noted in renal biopsies from patients with nephropathic cystinosis. In vitro studies performed in cystinotic fibroblasts and renal proximal tubular cells support a role for apoptosis of the glomerulotubular junction, and we have further extended these studies to human native cystinotic kidney specimens. We performed semi-quantitative analysis of tubular density in kidney biopsies from patients with nephropathic cystinosis and demonstrated a significant reduction (p=0.0003) in the number of proximal tubules in the kidney tissue of patients with cystinosis compared to normal kidneys and kidneys with other causes of renal injury; this reduction appears to be associated with the over-expression of caspase-4. This study provides the first quantitative evidence of a loss of proximal tubules in nephropathic cystinosis and suggests a possible role of caspase-4 in the apoptotic loss of proximal tubular cells. Further work is needed to elucidate if this injury mechanism may be causative for the progression of renal functional decline in nephropathic cystinosis.
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Authors | Poonam Sansanwal, Neeraja Kambham, Minnie M Sarwal |
Journal | Pediatric nephrology (Berlin, Germany)
(Pediatr Nephrol)
Vol. 25
Issue 1
Pg. 105-9
(Jan 2010)
ISSN: 1432-198X [Electronic] Germany |
PMID | 19705160
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Chemical References |
- CASP4 protein, human
- Caspases, Initiator
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Topics |
- Acute Kidney Injury
(metabolism, pathology)
- Apoptosis
- Caspases, Initiator
(metabolism)
- Child
- Cystinosis
- Fanconi Syndrome
- Glomerulosclerosis, Focal Segmental
(enzymology, pathology)
- Granulomatosis with Polyangiitis
(enzymology, pathology)
- Humans
- Kidney Tubular Necrosis, Acute
(enzymology, pathology)
- Kidney Tubules, Proximal
(enzymology, pathology)
- Nephrotic Syndrome
(enzymology, pathology)
- Vesico-Ureteral Reflux
(enzymology, pathology)
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