Doubling of serum creatinine and the risk of cardiovascular outcomes in patients with chronic kidney disease and type 2 diabetes mellitus: a cohort study

Abstract Aims/hypothesis In previous work, we reported the HR for the risk (95% CI) of the secondary kidney composite endpoint (time to first event of doubling of serum creatinine from baseline, renal dialysis/transplant or renal death) with ertugliflozin compared with placebo as 0.81 (0.63, 1.04). The effect of ertugliflozin on exploratory kidney-related outcomes was evaluated using data from the eValuation of ERTugliflozin effIcacy and Safety CardioVascular outcomes (VERTIS CV) trial (NCT01986881). Methods Individuals with type 2 diabetes mellitus and established atherosclerotic CVD were randomised to receive ertugliflozin 5 mg or 15 mg (observations from both doses were pooled), or matching placebo, added on to existing treatment. The kidney composite outcome in VERTIS CV (reported previously) was time to first event of doubling of serum creatinine from baseline, renal dialysis/transplant or renal death. The pre-specified exploratory composite outcome replaced doubling of serum creatinine with sustained 40% decrease from baseline in eGFR. In addition, the impact of ertugliflozin on urinary albumin/creatinine ratio (UACR) and eGFR over time was assessed. Results A total of 8246 individuals were randomised and followed for a mean of 3.5 years. The exploratory kidney composite outcome of sustained 40% reduction from baseline in eGFR, chronic kidney dialysis/transplant or renal death occurred at a lower event rate (events per 1000 person-years) in the ertugliflozin group than with the placebo group (6.0 vs 9.0); the HR (95% CI) was 0.66 (0.50, 0.88). At 60 months, in the ertugliflozin group, placebo-corrected changes from baseline (95% CIs) in UACR and eGFR were −16.2% (−23.9, −7.6) and 2.6 ml min−1 [1.73 m]−2 (1.5, 3.6), respectively. Ertugliflozin was associated with a consistent decrease in UACR and attenuation of eGFR decline across subgroups, with a suggested larger effect observed in the macroalbuminuria and Kidney Disease: Improving Global Outcomes in Chronic Kidney Disease (KDIGO CKD) high/very high-risk subgroups. Conclusions/interpretation Among individuals with type 2 diabetes and atherosclerotic CVD, ertugliflozin reduced the risk for the pre-specified exploratory composite renal endpoint and was associated with preservation of eGFR and reduced UACR. Trial registration ClinicalTrials.gov NCT01986881 Graphical abstract

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Inequalities in the Global Burden of Chronic Kidney Disease Due to Type 2 Diabetes Mellitus: An Analysis of Trends from 1990 to 2019

International Journal of Environmental Research and Public Health ◽

10.3390/ijerph18094723 ◽

2021 ◽

Vol 18 (9) ◽

pp. 4723

Author(s):

Nóra Kovács ◽

Attila Nagy ◽

Viktor Dombrádi ◽

Klára Bíró

Keyword(s):

Diabetes Mellitus ◽

Type 2 Diabetes ◽

Chronic Kidney Disease ◽

Type 2 Diabetes Mellitus ◽

Kidney Disease ◽

Data Exchange ◽

Disease Burden ◽

Socioeconomic Development ◽

Developed Countries

The prevalence of type 2 diabetes mellitus (T2DM) and the burden of complications are increasing worldwide. Chronic kidney disease (CKD) is one serious complication. Our aim was to investigate the trends and inequalities of the burden of CKD due to T2DM between 1990 and 2019. Data were obtained from the Global Health Data Exchange database. Age-standardized incidence, mortality, and DALYs rates of CKD were used to estimate the disease burden across the Human Development Index (HDI). Joinpoint regression was performed to assess changes in trend, and the Gini coefficient was used to assess health inequality. A higher incidence was observed in more developed countries (p < 0.001), while higher mortality and DALYs rates were experienced in low and middle HDI countries in 2019 (p < 0.001). The trend of incidence has increased since 1990 (AAPC: 0.9–1.5%), while slight decrease was observed in low HDI countries in mortality (APC: −0.1%) and DALYs (APC: −0.2%). The Gini coefficients of CKD incidence decreased from 0.25 in 2006 to 0.23 in 2019. The socioeconomic development was associated with disease burden. Our findings indicate that awareness of complications should be improved in countries with high incidence, and cost-effective preventive, diagnostic, and therapeutic tools are necessary to implement in less developed regions.

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