Background: Diabetic kidney disease (DKD) affects about 40% of type 2 diabetes (T2DM) patients and is associated with an increased risk of ESKD and cardiovascular events, as well as an increased mortality. It’s essential to trace the progression of DKD in order to identify patients with the highest cardio-renal risk and chronic complications. The latter are in fact the main cause of mortality in diabetic patients and looking for new predictive indicators plays a key role in the attempt to improve the management of the patients themselves. Among the indicators of DKD progression, the rapid decline of glomerular filtration, which we indicate with the eGFR slope parameter (calculated as the difference between at least two eGFR values over a period of 1 year), is acquiring an increasingly important role. The eGFR slope is a dynamic measure of renal function that indicates how glomerular filtration varies over time. The eGFR slope can indicate both a positive slope, so an improvement in renal function, and a negative slope, so a decline in renal function. Aim: the aim of the present study is to evaluate, by means of a systematic review of the literature and a subsequent meta-analysis of the collected data, the association between variability of the eGFR slope, chronic complications and mortality of subjects with type 2 diabetes. We focused on how a rapid decline in eGFR slope may be associated with a higher risk of chronic complications of type 2 diabetes compared to patients in whom the eGFR slope is stable. The risk analysis aims to understand whether or not the slope of the eGFR can be defined as a predictive indicator of complications in T2DM. Materials and methods: The review and meta-analysis was conducted according to PRISMA guidelines considering published studies on patients with T2DM. Literature research was performed 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 (CV events, ESKD, microvascular events, all-cause mortality) and patients with steeper eGFR slope decline than subjects with stable eGFR. For CV events, HR 1.73 (1.43-2.08); for ESKD, HR 1.54 (1.45-1.64); for microvascular events HR 2.07 (1.57-2.73); for all-cause mortality, HR 2.31 (1.70-3.15). Conclusions: Our meta-analysis indicates an association between rapid eGFR decline and chronic diabetes complications, suggesting that eGFR slope variability significantly impacts the course of type 2 diabetic disease 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 diabetic patient should not focus exclusively on glycemic control, but it is also important to act in order to preserve renal function.
Presupposti dello studio: La nefropatia diabetica (DKD, Diabetic Kidney Disease) interessa circa il 40% dei pazienti con diabete di tipo 2 (T2DM), si associa ad aumentato rischio di End-Stage Kidney Disease (ESKD) e di eventi cardiovascolari, oltre che ad aumentata mortalità. Diventa fondamentale tracciare la progressione della DKD per individuare i pazienti con più alto rischio cardio-renale e di complicanze croniche. Quest’ultime sono infatti la causa principale di mortalità nei pazienti diabetici e la ricerca di nuovi indicatori predittivi riveste un ruolo importante nel tentativo di migliorare la gestione dei pazienti stessi. Tra gli indicatori di progressione della DKD sta acquisendo un ruolo sempre più importante il rapido declino della filtrazione glomerulare che indichiamo col parametro dell’eGFR slope (calcolato come differenza tra almeno due valori di eGFR in un arco di tempo tipicamente di 1 anno). L’eGFR slope è una misura dinamica di funzionalità renale indicante la rapidità di variazione nel tempo della filtrazione glomerulare. L’eGFR slope può indicare sia una curva positiva, e quindi un miglioramento della funzionalità renale, sia una curva negativa, e quindi un declino della funzionalità renale. Scopo: l’obiettivo di questo studio è valutare attraverso una revisione sistematica della letteratura e la successiva meta-analisi dei dati raccolti, l’associazione tra variazione dell’eGFR slope, complicanze croniche e mortalità dei soggetti affetti da diabete di tipo 2. In modo particolare ci si è soffermati su come un rapido declino dell’eGFR slope possa associarsi ad un rischio maggiore di complicanze croniche del diabete di tipo 2 rispetto ai pazienti in cui l’eGFR slope risulti stabile. In definitiva l’analisi di rischio ha lo scopo di valutare l’eGFR slope come indicatore predittivo di complicanze nel paziente con T2DM. Materiali e metodi: La revisione e la meta-analisi sono state condotte secondo le line guida PRISMA considerando studi pubblicati su pazienti con T2DM. La ricerca scientifica è stata svolta su PubMed da gennaio 2003 ad aprile 2023 con successiva selezione dei lavori scientifici secondo i criteri di inclusione. Risultati: Sono stati selezionati quindici studi per la meta-analisi. L’analisi del rischio come hazard ratio (HR) ha indicato un’associazione significativa tra tutti gli eventi considerati (eventi CV, ESKD, eventi microvascolari, tutte le cause di mortalità) e i pazienti con declino dell’eGFR slope più rapido rispetto ai soggetti con eGFR stabile. Per gli eventi CV, HR 1.73 (1.43-2.08); per ESKD, HR 1.54 (1.45-1.64); per gli eventi microvascolari HR 2.07 (1.57-2.73); per tutte le cause di mortalità, HR 2.31 (1.70-3.15). Conclusioni: questa meta-analisi indica una chiara associazione tra rapido declino dell’eGFR e complicanze croniche del diabete, suggerendo come la variabilità dell’eGFR slope impatti significativamente sull’andamento della patologia diabetica di tipo 2 e che l’eGFR slope debba essere considerato come un fattore predittivo per le complicanze croniche nei pazienti con T2DM. Alla luce dei risultati ottenuti appare chiaro che nella gestione terapeutica del paziente diabetico non ci si debba focalizzare esclusivamente sul controllo glicemico, ma sia importante agire anche per preservare la funzionalità renale.
eGFR slope, un nuovo predittore delle complicanze croniche del diabete di tipo 2. Revisione sistematica e meta-analisi
DEPPIERI, ELENA
2022/2023
Abstract
Background: Diabetic kidney disease (DKD) affects about 40% of type 2 diabetes (T2DM) patients and is associated with an increased risk of ESKD and cardiovascular events, as well as an increased mortality. It’s essential to trace the progression of DKD in order to identify patients with the highest cardio-renal risk and chronic complications. The latter are in fact the main cause of mortality in diabetic patients and looking for new predictive indicators plays a key role in the attempt to improve the management of the patients themselves. Among the indicators of DKD progression, the rapid decline of glomerular filtration, which we indicate with the eGFR slope parameter (calculated as the difference between at least two eGFR values over a period of 1 year), is acquiring an increasingly important role. The eGFR slope is a dynamic measure of renal function that indicates how glomerular filtration varies over time. The eGFR slope can indicate both a positive slope, so an improvement in renal function, and a negative slope, so a decline in renal function. Aim: the aim of the present study is to evaluate, by means of a systematic review of the literature and a subsequent meta-analysis of the collected data, the association between variability of the eGFR slope, chronic complications and mortality of subjects with type 2 diabetes. We focused on how a rapid decline in eGFR slope may be associated with a higher risk of chronic complications of type 2 diabetes compared to patients in whom the eGFR slope is stable. The risk analysis aims to understand whether or not the slope of the eGFR can be defined as a predictive indicator of complications in T2DM. Materials and methods: The review and meta-analysis was conducted according to PRISMA guidelines considering published studies on patients with T2DM. Literature research was performed 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 (CV events, ESKD, microvascular events, all-cause mortality) and patients with steeper eGFR slope decline than subjects with stable eGFR. For CV events, HR 1.73 (1.43-2.08); for ESKD, HR 1.54 (1.45-1.64); for microvascular events HR 2.07 (1.57-2.73); for all-cause mortality, HR 2.31 (1.70-3.15). Conclusions: Our meta-analysis indicates an association between rapid eGFR decline and chronic diabetes complications, suggesting that eGFR slope variability significantly impacts the course of type 2 diabetic disease 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 diabetic patient should not focus exclusively on glycemic control, but it is also important to act in order to preserve renal function.File | Dimensione | Formato | |
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https://hdl.handle.net/20.500.12608/46981