By applying on two-sample Mendelian randomization and systematic review and meta-analysis we investigated the association between caffeine and coffee intake with prevalent CKD and markers of renal function.

Material and methods:
For the individual data analysis we analysed the NHANES data on renal function markers and caffeine intake. MR was implemented by using summary-level data from the largest ever GWAS conducted on coffee intake (N=91,462) and kidney function.

Finally, we included the data of 18,436 participants, 6.9% had prevalent CKD (based on eGFR). Caffeine intake for general population was 131.1±1.1 mg. The percentage of participants with CKD, by caffeine quartile was 16.6% in the first (lowest) quartile, 13.9% in the second, 12.2% in the third and 11.0% in the top quartile (p<0.001). After adjustment, for increasing quartiles for caffeine consumption, mean urine albumin, albumin-creatinine ratio and estimated glomerular filtration rate (GFR) did not change significantly (p>0.234). In fully adjusted logistic regression models, there was no significant difference in chances of CKD prevalence (p-trend=0.745). In the same line, results of MR showed no impact of coffee intake on CKD (IVW=β: -0.0191, SE: 0.069, p=0.781), on eGFR (overall= IVW= β: -0.0005, SE: 0.005, p=0.926) both in diabetic (IVW= β: -0.006, SE: 0.009, p=0.478), and non-diabetic patients (IVW= β: -6.772, SE: 0.006, p=0.991). Results from the meta-analysis indicted that coffee consumption was not significantly associated with CKD (OR: 0.85, 95%CI 0.71-1.02, p=0.090, n=6 studies, I2=0.32).

By implementing on different strategies, we have highlighted no significant association between coffee consumption with renal function and chance of CKD.