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.