Innovation grant of Dutch Kidney Foundation for Swinkels and Kortman

Swinkels Dorine

Prof. Dorine Swinkels and Dr. Guus Kortman of the Translational Metabolic Laboratory (TML) have recently been awarded a € 100.000 innovation grant of the Dutch Kidney Foundation.  

undefinedChronic kidney disease (CKD) in its different stages has an estimated prevalence of 8-16% worldwide, indicating a global health issue. Patients with CKD and loss of kidney function are at increased risk for morbidity and mortality. The risks of CKD are attributed to ‘uremia’, an increased concentration of uremic retention solutes (called ‘toxins’) in the plasma. Recently, a colo-renal axis became clearly apparent and uremia has been associated with an altered gut microbiome composition and metabolism. This includes a decrease of beneficial gut microbiota members, an increase in potentially pathogenic members, and an increase in the production of uremic toxins.  

Iron deficiency anaemia is highly prevalent among CKD patients and has major health consequences. Therefore iron deficiency should be treated. Oral iron therapy can be successful when iron is adequately absorbed, and when not causing adverse effects on intestinal health and the renal disease. The same holds true for treatment of hyperphosphatemia with oral iron-based phosphate binders. Notably, from previous experiments we have strong indications that supplementary iron causes an increase in plasma uremic toxin levels via increased production of protein-derived uremic toxins by the gut microbiota. As uremic toxins are generally resistant against dialysis and are associated with mortality, cardiovascular disease and progression of CKD, the production of these toxins should not be stimulated in CKD patients.  

We hypothesize that oral iron supplementation in iron deficient predialysis CKD patients changes gut microbiome composition, and causes an increase in faecal and plasma uremic toxin levels. This will be investigated in a clinical pilot trial, in which predialysis CKD patients with iron deficiency will receive standard oral iron therapy. In addition, in the TIM-2 kinetic model for the human large intestine we will study the effect of a standard iron supplement and different iron-based phosphate binders on the gut microbiota composition and metabolism. In this model we will also assess the potential benefit of an adsorbent that bind uremic toxins in the colon during iron supplementation, and the use of prebiotics that could prevent iron-induced proteolytic activity.  

The role of the gut microbiota in renal disease becomes more and more visible and recognized in the renal scientific field, but yet very little is known on the pathogenic role of the gut microbiota in CKD. Our study will highly contribute to the evolving microbiota research in renal science. 

Collaborators:

-          Prof. dr. Jack Wetzels
-          Dr. Roos Masereeuw en Prof. Dr.  Frans Russel
-          Dr. Koen Venema


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