b Very strong evidence of association is defined as significant relative risk of 45 (o0.2) based on direct evidence with no major threats to validity. c Sparse if there is only one study or if total N o500. Imprecise if there is a low event rate (0 or 1 event) in either arm or confidence interval spanning a range 41. Adapted by permission from Macmillan Publishers Ltd: Kidney International. Uhlig K, Macleod A, Craig J et al. Grading evidence and recommendations for clinical practice guidelines in nephrology. A position statement from Kidney Disease: Improving Global Outcomes (KDIGO). Kidney Int 2006; 70: 2058 2065;110 accessed http:// methods for guideline development whether the CKD subgroup defined by kidney function or proteinuria measured at baseline (rather than after the start of treatment), whether or not analyses of subgroups were pre-specified before randomization, whether or not intervention and comparator groups were balanced within the CKD subgroup. The directness of the CKD subgroup analysis was graded on the basis of whether or not the CKD subgroup results of trials that were not specifically designed for CKD were applicable to patients with CKD and also whether or not a test for interaction by baseline kidney function (or the level of proteinuria) was performed. Quality of the main study: A. Good B. Fair C. Poor Is CKD subgroup defined by kidney function or proteinuria measured at baseline? If yes, do not downgrade for subgroup. If no, reject or downgrade for subgroup by 1 or 2 levels based on the risk of bias. Is CKD subgroup pre-specified before secondary analysis? If no, is the standard definition of CKD , or the presence of proteinuria) used? If yes, do not downgrade for subgroup. If yes, do not downgrade for subgroup. 