Malnutrition Risk in Kidney Recipients Treated With Mycophenolate Mofetil Is Associated With IMPDH1 rs2278294...

Malnutrition is known to increase morbidity and mortality in renal transplant recipients, whereas little is known about genetic predisposition to low body mass index (BMI) in the transplant setting. Inosine monophosphate dehydrogenase (IMPDH) regulates intracellular fat accumulation, pre-adipicytes maturation, and is a target of mycophenolic acid (MPA) used as a standard immunosuppressant. We hypothesized that MPA may interfere with fat tissue formation and weight gain in kidney transplant recipients and this process may be modified by IMPDH1 or IMPDH2 (genes encoding constitutive and inducible IMPDH) small nucleotide polymorphism variants.

In an observational longitudinal study of kidney transplant recipients treated with mycophenolate mofetil, genetic factors were IMPDH1 (rs2278294, rs2278293) and IMPDH2 (rs11706052) allelic variants, the main outcome was the time-dependent change in BMI, and secondary outcomes were occurrence of BMI below 18.5 or 20 kg/m².

In a study group of 190 patients, no association was found between BMI changes and rs11706052 and rs2278293 variants. In terms of rs2278294, we found that allele G was associated with significantly slower BMI gain in a dominant model of inheritance. Concerning secondary endpoints, none of the AA carriers were underweight at 6 months post-implantation, while at least 2% of G allele carriers were underweight. From the first post-transplant year, all AA carriers had BMI above 20 kg/m², while among G allele carriers at least 10% had BMI < 20 kg/m² by generalized estimating equations.

Based on our results, we postulate that MPA derivates influence post-transplant BMI and potentially also body fat content. In consequence, genotyping rs2278294 would potentially allow clinicians to personalize MPA treatment.