Chronic Inflammation and Kidney Disease
Chronic inflammation is a major risk factor for morbidity and mortality in general population and often accompanies chronic kidney disease (CKD).
Uric acid is a waste molecule formed at a final step during enzymatic break-down of purine nucleotides (Figure 1).
Concentration of uric acid in serum rises during inflammation as a result of dissolution of nuclear material from dead immune cells and damaged tissues. It can also rise due to poor elimination (2/3 in the kidney and 1/3 in the gut) or excessive intake of purine-rich food.
CKD and conditions clustering with CKD, such as diabetes, metabolic syndrome, cardio-vascular and autoimmune diseases, are often accompanied by elevated serum uric acid. The prevalence of hyperuricemia in the general adult population of Tromsø is approximately 20%.
Although a common condition, hyperuricemia is not an innocent bystander or a simple biochemical marker of an on-going inflammation, unhealthy lifestyle or insufficient elimination. High uric acid concentrations can contribute to tissue damage as this substance is poorly soluble and precipitates readily into needle-like crystals (Figure 2). The crystals are highly pro-inflammatory per se but can also contributes to tissue damage by obstructing bodies’ channels. If formed in the urinary tract, they can lead to considerable kidney damage and in many patients to agonizing pain. Urolithiasis is a condition that often necessitates emergency treatment including surgery, in the majority of cases in relatively young and otherwise healthy individuals aged 20 to 50.
We investigate causes and effects of elevated serum uric acid. Our sub-projects include studies of gut microbiome and lifestyle-related factors such as diet and oral health in the pathogenesis of hyperuricemia, and incorporate both in vitro experiments and epidemiological research of longitudinal association between hyperuricemia, morbidity and mortality.
We have recently developed a new LC-MS/MS method for assessment of several purine metabolites in biological fluids that can help to uncover the exact pathogenetic mechanism behind hyperuricemia (overproduction vs reduced elimination) in an individual patient. Such information would allow risk-based patient stratification and help to tailor treatment to individual needs.
It is our hope that the project will provide valuable knowledge both for reducing the risk of developing chronic kidney disease and for prevention of extra-renal pathologies. Our results showing involvement of the gut microbiota in uric acid metabolism open avenues for non-pharmacological treatment of hyperuricemia and its consequences, particularly relevant for those with already decreased kidney function where pharmacological treatment options are limited.