Glomerular adaptation after kidney transplantation

In renal transplantation, surrogate variables of low nephron endowment are associated with a decreased allograft survival. However, total glomerular number can only be precisely estimated in experimental models or autopsy studies because the whole kidney is necessary for this purpose. The combination of magnetic resonance imaging of the kidney and a renal biopsy allows estimating total glomerular number in vivo, and the application of this approach to stable renal allografts has shown that total glomerular number is a major determinant of graft function.Protocol biopsies performed in stable grafts have allowed the characterization of subclinical rejection (SCR) and chronic allograft nephropathy as well as their predictive value on graft outcome. However, glomerular adaptation after transplantation has not captured the interest of the transplant community despite only one kidney is transplanted and a large proportion of transplant recipients will receive an insufficient nephron number for their metabolic demand.Using protocol biopsies, it has been shown that glomeruli enlarge after transplantation to provide an adequate filtration surface area to the recipient metabolic demand. Glomerular size increases during the first year and this adaptation process is necessary to achieve an adequate renal function. This adaptation is impaired in patients with SCR and/or chronic allograft nephropathy. Furthermore, glomerulosclerosis is also increased in patients with impaired glomerular adaptation. Taken together, these data suggest that the primary target of SCR is the tubulointerstitial compartment leading to interstitial fibrosis/tubular atrophy and to impaired glomerular adaptation/glomerulosclerosis thereafter.