Diet, lifestyle and chronic kidney disease

Chronic kidney disease (CKD) is a rapidly growing global health problem, affecting 5-10% of the general population, and individuals with CKD have a substantially increased risk of morbi-mortality. Early detection and treatment can delay or prevent onset many of the adverse outcomes of CKD. However, due to insufficient knowledge about factors that drive CKD incidence, renal function decline and complications of CKD, our capacity to implement effective preventive strategies is limited. This thesis explores associations of dietary/lifestyle risk factors with kidney dysfunction and diet-related outcomes. Study I investigated the associations between dietary fiber and systemic inflammation, kidney function and mortality risk. We found that higher dietary fiber intake was associated with better renal function and lower inflammation. Higher fiber intake was also associated with better survival, especially in individuals with manifest CKD. Study II investigated the implications of circulating phosphate levels, reflecting in part dietary intake of phosphorus, on the risk of adverse clinical outcomes in patients with manifest cardiovascular disease (CVD). We found that both higher and lower phosphate levels associated with increased risk of adverse outcomes during the index CVD hospitalization and within one-year post-discharge. Risk associations were already present in the normal-range serum phosphate levels. Study III addressed the pro-inflammatory load of the diet as a potential cause of kidney dysfunction. By combining putatively pro-inflammatory and anti-inflammatory effects of nutrients, vitamins, and trace elements, a dietary pattern was generated that correlated with both renal function and systemic inflammatory biomarkers. We found that pro-inflammatory diet associated with lower kidney function and that the association between this dietary pattern and renal function was substantially mediated by systemic inflammation. Study IV addressed the association between dietary acid load and mortality in the community. Both excessive dietary alkalinity and acidity, showed weak associations with mortality in a U-shaped fashion. An acid-base balanced diet was associated with the minimum mortality rate. However, the magnitude of mortality reduction was modest, suggesting that dietary modifications of the alkalinity of the diet may not be very relevant overall to reduce mortality risk. Study V investigated whether the association between obesity and incident CKD affected by genetic confounding and/or explained by obesity-associated diabetes among twins. We observed that controlling for shared risk factors between twin pairs minimally affected the association between body mass index (BMI) and CKD. In twins with discordant BMI, heavier siblings had a higher adjusted incidence rate of CKD than leaner ones. After adjusting for diabetes development, the strength of the association was reduced (suggesting effect mediation), but remained statistically and clinically significant. We concluded that a higher BMI, irrespective of genetic confounding or incident diabetes, was associated with CKD. LIST OF SCIENTIFIC PAPERS This thesis is based on the following papers. They are referred to in the text by their Roman