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Author Interviews


Authors' Interview:

Karl Skorecki, MD

Professor of Medicine/Nephrology

MD, 1977 - University of Toronto


Walter G. Wasser, MD
Hadassah University Hospital, Ein Kerem, Jerusalem 
Rambam Health Care Campus, Haifa



APOL1 allelic variants are associated with lower age of dialysis initiation and thereby increased dialysis vintage in African and Hispanic Americans with non-diabetic end-stage kidney disease

Shay Tzur ,Saharon Rosset, Karl Skorecki, Walter G. Wasser Nephrol. Dial. Transplant. doi: 10.1093/ndt/gfr796s

What is APOL1?

APOL1 is an allelic variation discovered on chromosome 22 consisting of 2 mutations.

It was initially described  two years ago by two research groups working separately, one of them ours. It is probably the major cause of non-diabetic kidney disease in patients of African ancestry and explains much of the increased risk of these types of kidney disease in African and Hispanic Americans from Puerto-Rico and the Dominican Republic.

Approximately 12 % of African-Americans have 2 APOL1 risk alleles in the general population; but in ESKD non-diabetic etiologies the frequencies are dramatically higher: ~50% in hypertensive ESKD, focal segmental glomerulosclerosis and HIV related kidney disease of the HVAN or FSGS variet.y

These alleles arose in western and southern continental Africa and have been shown to be absent in patients from Ethiopia, located in eastern Africa.

These allelic variants were shown to protect from Trypanosoma brucei rhondesiense in the heterozygous state explaining the selection pressures causing this variant to rise to unusually high population frequencies.

What are the main findings of the report?

In this report, we found:

  • That African and Hispanic Americans with 2 APOL1 Risk Alleles began dialysis >9 years earlier than those without risk alleles. This indicates that these patients have a distinct disease related to the APOL1 gene. The mechanism of the disease, is as of yet, not clear.

  • That an increased survival in these patients on dialysis was explained by the beginning of dialysis at younger ages and that APOL1 did not explain the increases in dialysis survival ("dialysis survival paradox") seen in African Americans over the past few decades.

One of the risk alleles (G1) shows an intermediate effect in lowering dialysis age even with just one risk allele.

What should clinicians and patients take away from this report?

We are beginning to dissect the genetic basis of kidney disease in populations such as African and Hispanic Americans which will hopefully eventually lead to better and more specific kidney disease treatments. Since the lifetime risk of developing kidney disease in normal individuals with 2 risk alleles is <5%, there are clearly other genetic and environmental factors that modulate this increased risk.

As long suspected by many nephrologists, hypertensive kidney disease in patients from at-risk populations, may indicate an underlying glomerulosclerosis and study of these patients may show differences in clinical features of the disease such as response to various different anti-hypertensives or progression of kidney disease.

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