Dataset Information

Improvement in Mortality and End-Stage Renal Disease in Patients With Type 2 Diabetes After Acute Kidney Injury Who Are Prescribed Dipeptidyl Peptidase-4 Inhibitors.

ABSTRACT:

Objective

To focus on the potential beneficial effects of the pleiotropic effects of dipeptidyl peptidase-4 inhibitors (DPP4is) on attenuating progression of diabetic kidney disease in reducing the long-term effect of the acute kidney injury (AKI) to chronic kidney disease (CKD) transition.

Patients and methods

Data from the National Health Insurance Research Database from January 1, 1999, to July 31, 2011, were analyzed, and patients with diabetes weaning from dialysis-requiring AKI were identified. Cox proportional hazards models and inverse-weighted estimates of the probability of treatment were used to adjust for treatment selection bias. The outcomes were incident end-stage renal disease (ESRD) and mortality, major adverse cardiovascular events, and hospitalized heart failure.

Results

Of a total of 6165 patients with diabetes weaning from dialysis-requiring AKI identified, 5635 (91.4%) patients were DPP4i nonusers and 530 (8.6%) patients were DPP4i users. Compared with DPP4i nonusers, DPP4i users had a lower risk of ESRD (hazard ratio, 0.81; 95% CI, 0.70-0.94; P=.04) and all-cause mortality (hazard ratio, 0.28; 95% CI, 0.23-0.34; P<.001) after adjustments for CKD, advanced CKD, and angiotensin-converting enzyme inhibitor or angiotensin II receptor blocker use. In contrast, the risk of major adverse cardiovascular events and hospitalized heart failure did not differ significantly between groups.

Conclusion

Dipeptidyl peptidase-4 inhibitor users had a lower risk of ESRD and mortality than did nonusers among patients with diabetes after weaning from dialysis-requiring AKI. Therefore, a prospective study of AKI to CKD transitions after episodes of AKI is needed to optimally target DPP4i interventions.

SUBMITTER: Chen CY

PROVIDER: S-EPMC7126857 | biostudies-literature | 2018 Dec

REPOSITORIES: biostudies-literature

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Publications

Improvement in Mortality and End-Stage Renal Disease in Patients With Type 2 Diabetes After Acute Kidney Injury Who Are Prescribed Dipeptidyl Peptidase-4 Inhibitors.

Chen Cheng-Yi CY Wu Vin-Cent VC Lin Cheng-Jui CJ Lin Chih-Sheng CS Pan Chi-Feng CF Chen Han-Hsiang HH Lin Yu-Feng YF Huang Tao-Min TM Chen Likwang L Wu Chih-Jen CJ

Mayo Clinic proceedings 20181019 12

<h4>Objective</h4>To focus on the potential beneficial effects of the pleiotropic effects of dipeptidyl peptidase-4 inhibitors (DPP4is) on attenuating progression of diabetic kidney disease in reducing the long-term effect of the acute kidney injury (AKI) to chronic kidney disease (CKD) transition.<h4>Patients and methods</h4>Data from the National Health Insurance Research Database from January 1, 1999, to July 31, 2011, were analyzed, and patients with diabetes weaning from dialysis-requiring ...[more]

PMID: 30343892

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Project description:Emerging evidence suggests that dipeptidyl peptidase-4 (DPP-4) inhibitors used to treat type 2 diabetes may have nephroprotective effects beyond the reduced renal risk conferred by glycemic control. DPP-4 is a ubiquitous protein with exopeptidase activity that exists in cell membrane-bound and soluble forms. The kidneys contain the highest levels of DPP-4, which is increased in diabetic nephropathy. DPP-4 inhibitors are a chemically heterogeneous class of drugs with important pharmacological differences. Of the globally marketed DPP-4 inhibitors, linagliptin is of particular interest for diabetic nephropathy as it is the only compound that is not predominantly excreted in the urine. Linagliptin is also the most potent DPP-4 inhibitor, has the highest affinity for this protein, and has the largest volume of distribution; these properties allow linagliptin to penetrate kidney tissue and tightly bind resident DPP-4. In animal models of kidney disease, linagliptin elicited multiple renoprotective effects, including reducing albuminuria, glomerulosclerosis, and tubulointerstitial fibrosis, independent of changes in glucagon-like peptide-1 (GLP-1) and glucose levels. At the molecular level, linagliptin prevented the pro-fibrotic endothelial-to-mesenchymal transition by disrupting the interaction between membrane-bound DPP-4 and integrin β1 that enhances signaling by transforming growth factor-β1 and vascular endothelial growth factor receptor-1. Linagliptin also increased stromal cell derived factor-1 levels, ameliorated endothelial dysfunction, and displayed unique antioxidant effects. Although the nephroprotective effects of linagliptin are yet to be translated to the clinical setting, the ongoing Cardiovascular and Renal Microvascular Outcome Study with Linagliptin in Patients with Type 2 Diabetes Mellitus (CARMELINA®) study will definitively assess the renal effects of this DPP-4 inhibitor. CARMELINA® is the only clinical trial of a DPP-4 inhibitor powered to evaluate kidney outcomes.

Project description:ContextChronic kidney disease (CKD) is prevalent in older individuals, but the risk implications of low estimated glomerular filtration rate (eGFR) and high albuminuria across the full age range are controversial.ObjectiveTo evaluate possible effect modification (interaction) by age of the association of eGFR and albuminuria with clinical risk, examining both relative and absolute risks.Design, setting, and participantsIndividual-level meta-analysis including 2,051,244 participants from 33 general population or high-risk (of vascular disease) cohorts and 13 CKD cohorts from Asia, Australasia, Europe, and North/South America, conducted in 1972-2011 with a mean follow-up time of 5.8 years (range, 0-31 years).Main outcome measuresHazard ratios (HRs) of mortality and end-stage renal disease (ESRD) according to eGFR and albuminuria were meta-analyzed across age categories after adjusting for sex, race, cardiovascular disease, diabetes, systolic blood pressure, cholesterol, body mass index, and smoking. Absolute risks were estimated using HRs and average incidence rates.ResultsMortality (112,325 deaths) and ESRD (8411 events) risks were higher at lower eGFR and higher albuminuria in every age category. In general and high-risk cohorts, relative mortality risk for reduced eGFR decreased with increasing age; eg, adjusted HRs at an eGFR of 45 mL/min/1.73 m2 vs 80 mL/min/1.73 m2 were 3.50 (95% CI, 2.55-4.81), 2.21 (95% CI, 2.02-2.41), 1.59 (95% CI, 1.42-1.77), and 1.35 (95% CI, 1.23-1.48) in age categories 18-54, 55-64, 65-74, and ≥75 years, respectively (P <.05 for age interaction). Absolute risk differences for the same comparisons were higher at older age (9.0 [95% CI, 6.0-12.8], 12.2 [95% CI, 10.3-14.3], 13.3 [95% CI, 9.0-18.6], and 27.2 [95% CI, 13.5-45.5] excess deaths per 1000 person-years, respectively). For increased albuminuria, reduction of relative risk with increasing age was less evident, while differences in absolute risk were higher in older age categories (7.5 [95% CI, 4.3-11.9], 12.2 [95% CI, 7.9-17.6], 22.7 [95% CI, 15.3-31.6], and 34.3 [95% CI, 19.5-52.4] excess deaths per 1000 person-years, respectively by age category, at an albumin-creatinine ratio of 300 mg/g vs 10 mg/g). In CKD cohorts, adjusted relative hazards of mortality did not decrease with age. In all cohorts, ESRD relative risks and absolute risk differences at lower eGFR or higher albuminuria were comparable across age categories.ConclusionsBoth low eGFR and high albuminuria were independently associated with mortality and ESRD regardless of age across a wide range of populations. Mortality showed lower relative risk but higher absolute risk differences at older age.

Dataset Information

Improvement in Mortality and End-Stage Renal Disease in Patients With Type 2 Diabetes After Acute Kidney Injury Who Are Prescribed Dipeptidyl Peptidase-4 Inhibitors.

Objective

Patients and methods

Results

Conclusion

Publications

Improvement in Mortality and End-Stage Renal Disease in Patients With Type 2 Diabetes After Acute Kidney Injury Who Are Prescribed Dipeptidyl Peptidase-4 Inhibitors.

Similar Datasets

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