Team of FAU researchers discovers new risk factor for chronic kidney diseases


Hypoxia could accelerate chronic kidney failure with certain gene variants

Chronic kidney diseases are on the rise worldwide and people of African descent are more likely to be affected due to two gene variants. A team of researchers led by PD Dr. Johannes Schödel and Dr. Steffen Grampp from the Chair of Internal Medicine IV at FAU and the Department of Medicine 4 – Nephrology and Hypertension at Universitätsklinikum Erlangen has now discovered that hypoxia (lack of oxygen) in the cells of the kidney is a further risk factor that stimulates the risk gene variants and can accelerate chronic kidney failure. Certain medications that are currently used for treating chronic kidney insufficiency could prove problematic for patients with these gene variants. The research has now been published in the renowned journal “Kidney International”.

Many sufferers of chronic kidney disease can only survive with the help of dialysis or a kidney transplant. The most significant risk factors for developing chronic kidney disease are diabetes, high blood pressure and cardiac insufficiency, otherwise known as heart failure. However, people with dark skin have a significantly higher risk of developing chronic kidney disease compared to those with light skin. They also suffer from more aggressive forms of kidney disease. This is caused by two gene variants.

Chronic kidney disease and gene variants

A genome-wide association study in 2010 demonstrated a connection between two variants of the apolipoprotein 1 gene (APOL1) on chromosome 22 with the increased risk of kidney disease in people of African descent. Both these gene variants probably developed because they provide an evolutionary advantage: They protect people with these gene variants from African sleeping sickness and their pathogens, trypanosoma brucei rhodesiense and gambiense.

The disadvantage is that if these gene variants are expressed in kidney cells, this leads to the progression of kidney diseases known as apolipoprotein L1 nephropathy. Disease progression, however, varies from individual to individual. Accompanying factors such as viral infections that stimulate APOL1 gene expression can accelerate it.

Hypoxia as a newly-discovered risk factor

As part of the Transregional Collaborative Research Center TRR374 (sub-project C5) and in conjunction with researchers at Münster University Hospital, the research team at Universitätsklinikum Erlangen were able to demonstrate for the first time that hypoxia (lack of oxygen) accelerates both the gene expression of APOL1 and the pathogenic variants in kidney cells, thereby accelerating the development of chronic kidney diseases. Hypoxia in the kidney occurs with anemia or during acute kidney failure. The research team identified a DNA element that is located near the APOL1 gene and that regulates this gene. If certain proteins that become active during apoxia known as hypoxia-inducible factors (HIF) bind to the DNA element, this increases the expression of the APOL1 gene, meaning that it becomes more active. The increased expression of the APOL1 gene, however, could damage the kidneys even further.

As a consequence of the discovery, the research team led by Johannes Schödel and Steffen Grampp pinpointed another problem. New medication for people with chronic kidney insufficiency and renal anemia (anemia caused by chronic kidney failure) function like hypoxia and thus activate the HIF. This stimulates the formation of red blood cells through several stages and increases the oxygen content of the blood. APOL1 is activated at the same time, however – including the gene variants that can accelerate chronic kidney failure. This means that medication for stabilizing HIF should initially only be given with care to people who carry these risk gene variants.

Further information:


PD Dr. Johannes Schödel

Department of Medicine 4 – Nephrology and Hypertension and Chair of Internal Medicine IV