PATHOPHYSIOLOGY OF CHRONIC ALLOGRAFT NEPHROPATHY

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This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Elderly cadaveric donors >60 yrs-old are reluctantly used for kidney transplantation (Tx), because an aged renal allograft has been shown to be associated with a short half-life. We now propose to elucidate the relationship between renal senescence and acceleration of chronic allograft nephropathy (CAN) in recipients of aged cadaver transplants. We will use physiological and morphometric techniques to elucidate glomerular function and structure in transplant recipients attending our post-transplant clinic. We wish to determine whether there are qualitative or quantitative differences between recipients of youthful (<40 yr) and aged (55 yr) kidney donors. This is a cross-sectional addition to our longitudinal (serial) study entitled "Renal Senescence and Transplantation," already approved by the GCRC (NIH grant DK064697). Our aim is to test the following four hypotheses: (1) That a reduction in the absolute glomerular number curtails the availability of surface area for filtration (S). (2) That (S) is further compromised by glomeruli that are no longer able to form glomerular filtrate by virtue of either global glomerulosclerosis or separation from the proximal tubule (so called "atubular glomeruli"). (3) That the ultrafiltration coefficient (Kf) of the remaining patent and filtering glomeruli is depressed because of impaired hydraulic permeability of glomerular capillary walls (k) and/or reduction in filtration surface area. (4) A combination of renal senescence and CAN leads to progressive and incremental glomerulopenia in allografts from aged donors. We will use physiologic and morphometric techniques, along with mathematical modeling and MRA to determine filtration capacity and glomerular number. Subjects with CAN, who underwent transplantation with a single youthful kidney, a single aged kidney, or two aged kidneys, and whose Tx kidneys are still functioning will be asked to participate in this study.