Blog entry by Meguid El Nahas
Growing evidence is implicating a genetic absis for CKD in African-Americans linked to mutations in the APOL1 gene. A genetic mutation that served sub-saharan Africans well some 10,000 years ago as it confered trypanolytic activity against trypanosoma brucei...but now comes to cost them a susceptibility to non diabetic CKD including primary and secondary FSGS (1).
More recently, it has also become apparent that such mutations in the APOL1 gene may confer increased susceptibility to renal allograft failure; not as much in black recipients but in relation to balck donors. Renal allografts with APOL1 G1 and G2 mutations variants have considerably shorter allograft survival (2).
Consequently, the question is now raised as to whether Blacks with such AOPL1 mutations should donate their kidneys or not? In two respects, first whether such allograft will have a poorer outcome, second, whether the donor, if young, would be susceptible later in life to a nephropathy on his/her remaining kidney. Those may develop the unfavorable CKD/FSGS phenotype later in life.
This concern applies to both living as well as deceased donors. Two (G1 and G2) APLO1 risk variant kidneys may be avoided or used where expanded criteria donor kidneys are considered, as they have a greater probability of early allograft failure.
In the era of rapid sequencing and PCR based genotyping, time may have come for a better genetic evaluation of kidney donors (3).
However, such approach whilst affordable and applicable in high economies is unlikely to be either practical or affordable in low and middle economy countries where most black individuals and those of African ancestry live...all too often medical guidelines and recommendations made in Western countries and Western publications overlook the fact that the world is not confined to the West, but also East and South...in those, genotyping of any kind is not an option, whilst renal transplantation may be a survival option in the absence of other forms of renal replacement therapies such as dialysis. Instead, a more careful clinical and laboratory evaluation of black donors is warranted, with careful family history (of CKD) souhgt, a careful evaluation of their kidney function and microalbuminuria, as well as more cautious, or agressive, management of these potentially higher risk of failure kidneys.
1. Genovese et al. Science 2010;329:841-45.
2. Reeves-Daniel et al. Am J Transpl 2011;11:1025-30.
3. Freedman and Julian. Kidney Int 2015; 87:671-73.