NDT Advance Access published online on March 10, 2008
Nephrology Dialysis Transplantation, doi:10.1093/ndt/gfn112
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Nephron number determines susceptibility to renal mass reduction-induced CKD in Lewis and Fisher 344 rats: implications for development of experimentally induced chronic allograft nephropathy
1 Department of Pediatrics 2 Department of Pulmonology, Semmelweis University, Budapest, Hungary 3 Department of Physiology and Functional Genomics and Department of Medicine, University of Florida, Gainesville, FL 4 Department of Pediatrics, West Virginia University 5 Toxicology and Molecular Biology Branch, National Institute of Occupational Safety and Health, Morgantown, West Virginia, USA
Correspondence and offprint requests to: Chris Baylis, Department of Physiology and Functional Genomics and Department of Medicine, 1600 SW Archer Road, Room M554, University of Florida, PO Box 100274, Gainesville, FL 36210, USA. Tel: +1-352-392-7869; Fax: +1-352-392-7935; E-mail: baylisc{at}ufl.edu
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Abstract |
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Background. The Fisher 344 (F344) rat kidney transplanted to a Lewis rat recipient is a common model of chronic renal allograft nephropathy (CAN); however, CAN does not develop when the Lewis kidney is grafted into a F344 recipient. In this study we investigated whether a difference in nephron number/glomerular volume exists between the strains that could contribute to a greater susceptibility to development of kidney disease in the F344.
Methods. Separate animals, male F344 and Lewis rats, were subjected to either sham surgery or right uni-nephrectomy and infarction of 2/3 of the left kidney, to produce a 5/6 ablation/infarction injury (5/6 A/I). Serial urinary protein excretions were measured, a terminal 24-h creatinine clearance was obtained and rats were killed 11 weeks after surgery and kidneys were harvested for pathology. Glomerular volumes were measured in the sham controls of each strain. Glomerular number was counted in separate, normal rats of each strain.
Results. The normal F344 had 
30% fewer glomeruli than Lewis rats that were larger in volume. The sham F344 had similar creatinine clearance and glomerular structure to the Lewis shams, although BP and urine protein excretion were higher. After 5/6 A/I the F344 developed more severe proteinuria and structural kidney damage. When factored for kidney weight, the F344 rats exhibited a greater compensatory hyperfiltration in response to 5/6 A/I, compared to Lewis.
Conclusions. The F344 strain is more vulnerable to development of progressive kidney damage due to 5/6 A/I, compared to the Lewis. This is likely due to the lower nephron number/greater glomerular volume of the F344 that may also account for the greater susceptibility to CAN exhibited by this strain.
Keywords: creatinine clearance; 5/6 renal ablation/infarction; glomerulosclerosis; proteinuria; rat strain
Received for publication: 3. 8.07
Accepted in revised form: 7. 2.08