Albuminuria, serum creatinine, and estimated glomerular filtration rate as predictors of cardio-renal outcomes in patients with type 2 diabetes mellitus and kidney disease: a systematic literature review

Background: Albuminuria, elevated serum creatinine and low estimated glomerular filtration rate (eGFR) are pivotal indicators of kidney decline. Yet, it is uncertain if these and emerging biomarkers such as uric acid represent independent predictors of kidney disease progression or subsequent outcomes among individuals with type 2 diabetes mellitus (T2DM). This study systematically examined the available literature documenting the role of albuminuria, serum creatinine, eGFR, and uric acid in predicting kidney disease progression and cardio-renal outcomes in persons with T2DM. Methods: Embase, MEDLINE, and Cochrane Central Trials Register and Database of Systematic Reviews were searched for relevant studies from January 2000 through May 2016. PubMed was searched from 2013 until May 2016 to retrieve studies not yet indexed in the other databases. Observational cohort or non-randomized longitudinal studies relevant to albuminuria, serum creatinine, eGFR, uric acid and their association with kidney disease progression, non-fatal cardiovascular events, and all-cause mortality as outcomes in persons with T2DM, were eligible for inclusion. Two reviewers screened citations to ensure studies met inclusion criteria. Results: From 2249 citations screened, 81 studies were retained, of which 39 were omitted during the extraction phase (cross-sectional [n = 16]; no outcome/measure of interest [n = 13]; not T2DM specific [n = 7]; review article [n = 1]; editorial [n = 1]; not in English language [n = 1]). Of the remaining 42 longitudinal study publications, biomarker measurements were diverse, with seven different measures for eGFR and five different measures for albuminuria documented. Kidney disease progression differed substantially across 31 publications, with GFR loss (n = 9 [29.0%]) and doubling of serum creatinine (n = 5 [16.1%]) the most frequently reported outcome measures. Numerous publications presented risk estimates for albuminuria (n = 18), serum creatinine/eGFR (n = 13), or both combined (n = 6), with only one study reporting for uric acid. Most often, these biomarkers were associated with a greater risk of experiencing clinical outcomes. Conclusions: Despite the utility of albuminuria, serum creatinine, and eGFR as predictors of kidney disease progression, further efforts to harmonize biomarker measurements are needed given the disparate methodologies observed in this review. Such efforts would help better establish the clinical significance of these and other biomarkers of renal function and cardio-renal outcomes in persons with T2DM.