APOL1 Risk Alleles Linked to CKD Progression: Contender for Top 10 of 2013

Top Nephrology Stories of 2013 imageIt’s that time of the year– Renal Fellow Network’s annual top stories in nephrology. My pick for top story of 2013 is the recent APOL1 paper by Parsa et al. While APOL1 is not a new story it is rapidly developing and has the potential to make a huge impact in the field of nephrology. This study by Parsa et al expands on our current understanding and was presented at ASN and published in the NEJM. One of the greatest disparities in medicine is that of African Americans as compared to whites who eventually develop end-stage renal disease (ESRD). African Americans have approximately 2X the risk of developing ESRD as compared to white patients. This is AFTER adjusting for socioeconomic status and clinical risk factors. What accounts for this increased risk? It has previously been reported that a region on chromosome 22 containing the gene encoding APOL1 have been implicated in the heightened risk among African American patients with HIVAN, FSGS, hypertensive CKD, and ESRD not attributed to diabetes. Furthermore, two common variants termed G1 and G2 encoded in the last exon of APOL1 strongly associate with this increased risk. Interestingly, these exact variants confer resistance to lethal Trypanosoma brucei infections or African sleeping sickness. These variants are common in individuals of recent African descent, but are rare in other populations. The current study by Parsa et al broaden our understanding of these risk alleles by demonstrating in the AASK cohort, having two copies of the disease-associated APOL1 allele was associated with a statistically significant increase in the rate of progression to ESRD or doubling of serum creatinine when compared with patients with either zero or one APOL1 risk allele. Next, the group examined the CRIC cohort, and again showed that African American patients with the two APOL1 risk alleles had statistically faster rate of eGFR decline as well as the composite outcome of ESRD or doubling of serum creatinine. Why does this story deserve contention for the top story of 2013? This study further establishes that APOL1 gene variants in African Americans are associated with decline of kidney function in two established cohorts.  If an effective therapy existed to target APOL1 this could have huge potential impact to patients with kidney disease. We still have a long way to go in understanding the biology of APOL1 in health and disease before an effective therapy could be deployed. One huge barrier is that mice do not have APOL1 and this will limit our ability to probe this system completely. Nonetheless, APOL1 has huge potential and I believe is a  contender for top nephrology story of 2013.

Go to Renal Fellow Network and vote for your top nephrology story of 2013!

Dr. Matthew A. Sparks
eAJKD Advisory Board member

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