PMCID: PMC3888310 DOI: 10.1093/ndt/gft387
BACKGROUND: Glomerular hyperfiltration is emerging as the key risk factor for progression of chronic kidney disease (CKD). Podocytes are exposed to fluid flow shear stress (FFSS) caused by the flow of ultrafiltrate within Bowman's space. The mechanism of hyperfiltration-induced podocyte injury is not clear. We postulated that glomerular hyperfiltration in solitary kidney increases FFSS over podocytes.
METHODS: Infant Sprague-Dawley rats at 5 days of age and C57BL/6J 14-week-old adult mice underwent unilateral nephrectomy. Micropuncture and morphological studies were then performed on 20- and 60-day-old rats. FFSS over podocytes in uninephrectomized rats and mice was calculated using the recently published equation by Friedrich et al. which includes the variables-single nephron glomerular filtration rate (SNGFR), filtration fraction (f), glomerular tuft diameter (2RT) and width of Bowman's space (s).
RESULTS: Glomerular hypertrophy was observed in uninephrectomized rats and mice. Uninephrectomized rats on Day 20 showed a 2.0-fold increase in SNGFR, 1.0-fold increase in 2RT and 2.1-fold increase in FFSS, and on Day 60 showed a 1.9-fold increase in SNGFR, 1.3-fold increase in 2RT and 1.5-fold increase in FFSS, at all values of modeled 's'. Similarly, uninephrectomized mice showed a 2- to 3-fold increase in FFSS at all values of modeled SNGFR.
CONCLUSIONS: FFSS over podocytes is increased in solitary kidneys in both infant rats and adult mice. This increase is a consequence of increased SNGFR. We speculate that increased FFSS caused by reduced nephron number contributes to podocyte injury and promotes the progression of CKD.
Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association
Animals; Filtration; Glomerular Filtration Rate; Kidney; Male; Mice; Mice, Inbred C57BL; Nephrons; Podocytes; Rats; Rats, Sprague-Dawley; Stress, Mechanical; Urogenital Abnormalities
fluid flow shear stress; glomerular hyperfiltration; podocyte; solitary kidney
Srivastava, T., Celsi, G. E., Sharma, M., Dai, H., McCarthy, E. T., Ruiz, M., Cudmore, P. A., Alon, U. S., Sharma, R., Savin, V. A. Fluid flow shear stress over podocytes is increased in the solitary kidney. Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association 29, 65-72 (2014).