Diet, lifestyle and chronic kidney disease

Chronic kidney disease (CKD) is a rapidly growing public 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. Identification of modifiable risk factors that could reduce the adverse outcomes in this vulnerable population is of great importance. This thesis explores associations of dietary/lifestyle risk factors with kidney dysfunction and diet-related outcomes.

Study I investigates the associations between dietary fiber and systemic inflammation, kidney function and mortality risk. We found that higher dietary fiber intake was associated with better kidney function and lower inflammation markers in community-dwelling individuals. A high fiber intake is associated with lower mortality risk, especially in individuals with manifest CKD. Study II investigates 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). In patients with suspected acute coronary syndrome, both higher and lower phosphate levels associated with increased risk of adverse outcomes during the index hospitalization and within one year post-discharge. The risk association was present already with serum phosphate concentrations within the normal range. Study III addresses 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 markers. We found that a pro-inflammatory diet associates with low kidney function and that the association between this dietary pattern and kidney function is substantially mediated by systemic inflammation.

Study IV addresses the association between dietary acid load and mortality in the community. Excess diet alkalinity and acidity both showed weak associations with increased mortality in a U-shape fashion. An acid-base balanced diet was associated with the lowest mortality risk. However, the magnitude of mortality reduction was modest, suggesting that dietary modifications of the alkalinity of the diet alkalinity may not be very relevant overall to reduce mortality risk. Study V investigates whether the association between obesity and incident CKD is affected by genetic confounding and/or explained by obesity-associated diabetes among twins. We observe 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 conclude that a higher BMI, irrespective of genetic confounding or incident diabetes, is associated with CKD.

List of scientific papers

I. Xu H, Huang X, Risérus U, Krishnamurthy VM, Cederholm T, Arnlöv J, Lindholm B, Sjögren P, Carrero JJ. Dietary fiber, kidney function, inflammation, and mortality risk. Clinical journal of the American Society of Nephrology. 2014 9;12 2104-10.
https://doi.org/10.2215/CJN.02260314

II. Xu H, Evans M, Gasparini A, Szummer K, Spaak J, Ärnlöv J, Lindholm B, Jernberg T, Carrero JJ. Outcomes associated to serum phosphate levels in patients with suspected acute coronary syndrome. International journal of cardiology. 2017 245; 20-26.
https://doi.org/10.1016/j.ijcard.2017.07.050

III. Xu H, Sjögren P, Ärnlöv J, Banerjee T, Cederholm T, Risérus U, Lindholm B, Lind L, Carrero JJ. A pro-inflammatory diet is associated with systemic inflammation and reduced kidney function in elderly adults. Journal of nutrition. 2015 145;4 729-35.
https://doi.org/10.3945/jn.114.205187

IV. Xu H, Åkesson A, Orsini N, Hakansson N, Wolk A, Carrero JJ. Modest U-Shaped Association between Dietary Acid Load and Risk of All-Cause and Cardiovascular Mortality in Adults. Journal of nutrition. 2016 146;8 1580-5.
https://doi.org/10.3945/jn.116.231019

V. Xu H, R Kuja-Halkola, X Chen, P Magnusson, P Svensson, JJ Carrero. Impact of genetic confounding and incident diabetes in the association between body mass index and chronic kidney disease: a population-based Swedish twin study. [Submitted]