Is eGFR Slope a Novel Predictor of Chronic Complications of Type 2 Diabetes Mellitus? A Systematic Review and Meta-Analysis

Abstract

Background. Diabetic kidney disease affects approximately 40% of patients with type 2 diabetes mellitus (T2DM) and is associated with an increased risk of end-stage kidney disease (ESKD) and cardiovascular (CV) events, as well as increased mortality. Among the indicators of decline in renal function, the eGFR slope is acquiring an increasing clinical interest. The aim of this study was to evaluate, through a systematic review of the literature and meta-analysis of the collected data, the association between the decline of the eGFR slope, chronic complications, and mortality of T2DM patients, in order to understand whether or not the eGFR slope can be defined as a predictive indicator of complications in T2DM. Methods. The review and meta-analysis were conducted according to PRISMA guidelines considering published studies on patients with T2DM. A scientific literature search was carried out on PubMed from January 2003 to April 2023 with subsequent selection of scientific papers according to the inclusion criteria. Results. Fifteen studies were selected for meta-analysis. Risk analysis as hazard ratio (HR) indicated a significant association between all events considered (all-cause mortality, CV events, ESKD, and microvascular events) for patients with steeper eGFR slope decline than subjects with stable eGFR. Calculated HRs (with 95% CI) were as follows: for all-cause mortality, 2.31 (1.70-3.15); for CV events, 1.73 (1.43-2.08); for ESKD, 1.54 (1.45-1.64); and for microvascular events, 2.07 (1.57-2.73). Overall HR was 1.82 (1.72-1.92). Conclusions. An association between rapid eGFR decline and chronic diabetes complications was demonstrated, suggesting that eGFR slope variability significantly impacts the course of T2DM and that eGFR slope should be considered as a predictor for chronic complications in patients with T2DM. According to the obtained results, the therapeutic management of the patient with diabetes should not focus exclusively on glycaemic control, and particular attention should be paid to preserve renal function.

Evaluation of Cardiovascular Disease Risk in Patients with Type 2 Diabetes Mellitus Using Clinical Laboratory Markers

“…It is also worth noting that when eGFR was excluded from the second model, increased serum creatinine levels were associated with increased cardiovascular risk in T2DM patients with statistical significance. These results are consistent with the findings of similar earlier studies [ 30 , 31 ] and demonstrates the significance of these laboratory parameters in assessing cardiovascular risk in patients with T2DM.…”

Outcome Measures of Clinical Trials in Pediatric Chronic Kidney Disease

“…The Kidney Disease Outcomes Quality Initiative (KDOQI) guidelines describe progression as either (1) a decline in kidney function observed in a follow-up patient or (2) the onset of kidney failure, with the latter defined by the need for KRT to manage symptoms of renal function decline or complications [20]. While this definition is clear, its application in clinical trials can be complex [21,22]. As a result, some clinical trials adopt alternative definitions, such as a GFR decrease by 50% or 25% or a doubling of serum creatinine levels [23][24][25].…”

“…Moreover, some experts suggest that the rate of GFR decline should be considered in addition to the extent of the decline. Consequently, certain studies have utilized the rate of change per year or the eGFR slope [22]. The National Institute for Health and Care Excellence (NICE) in the UK recommends performing at least three GFR tests within a 90-day period and defines progression as an eGFR decrease of >5 mL/min/1.73 m 2 within one year or >10 mL/min/1.73 m 2 within five years [26].…”