A Review of the Renoprotective Effects of Novel Antidiabetic Agents

Leite, Kelsey; Long, Allissa M.; Ostroff, Marissa; Borges, Leanna; Braden, Gregory

doi:10.1177/0897190020902344

Cited by 6 publications

(3 citation statements)

References 24 publications

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“…While novel treatment strategies for cardio-renal outcomes such as SGLT-2 inhibitors are effective in lowering rest albuminuria [29,30], their effect on exercise induced excretion of albumin is not entirely clear. We suggest that monitoring exercise induced levels of albuminuria may serve as a screening tool for pre-diabetic and diabetic individuals who require early initiation of such renal protective therapies [31,32].…”

Section: Discussionmentioning

confidence: 99%

Exercise-induced albuminuria increases over time in individuals with impaired glucose metabolism

Brzezinski

Friedensohn

Shapira

et al. 2020

Cardiovasc Diabetol

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Background: Exercise induced albuminuria (EiA) is elevated in patients with metabolic dysfunction and diabetes, and may serve as an early biomarker for endothelial dysfunction and "kidney reserve". However, the change in EiA levels over time and its interaction with metabolic dysfunction and glucose metabolism has never been studied. Therefore, we sought to determine EiA levels over time in a cohort of individuals attending a routine annual health survey. Methods: We prospectively enrolled 412 patients attending an annual healthy survey at our Medical Center. We collected urine samples for albumin and creatinine measurements before and immediately after completing an exercise stress test, along with multiple physiologic and metabolic parameters. Participants returned to a second follow up visit after a mean follow up period of 3 years (± 1.7 SD). Results: Patients with diagnosed diabetes and subjects with HbA1c ≥ 6.5% significantly increased their EiA over time (median [IQR] change between visits = 19.5 [− 10.4-56.1] vs. − 1.1 [− 12.7-4.9] (p = 0.049) for diabetics vs non-diabetics respectively). Moreover, a diabetes diagnosis was significantly associated with a high increase in EiA over time (top 10th percentile) even after adjusting for age, BMI, eGFR, METs, self-reported history of heart disease, systolic and diastolic blood pressure; OR = 4.4 (1.01-19.3 95% CI) (p = 0.049). Finally, elevated fasting blood glucose (≥ 100 mg/dl) was the strongest and only significant predictor for a greater increase in EiA over time after adjusting for all five metabolic syndrome components; blood glucose, waist circumference, blood triglycerides, HDL cholesterol, and BP criteria; OR = 4.0 (1.6-9.8 95% CI) (p < 0.01). Conclusions: Patients with diabetes and/or elevated fasting blood glucose increase their exercise-induced urinary albumin excretion over time. The ability of EiA to predict major clinical outcomes in patients with and without diabetes needs to be determined in future studies.

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Section: Discussionmentioning

confidence: 99%

Exercise-induced albuminuria increases over time in individuals with impaired glucose metabolism

Brzezinski

Friedensohn

Shapira

et al. 2020

Cardiovasc Diabetol

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“…To date, only a few classes of antidiabetic drugs could improve renal outcomes in large-scale randomized clinical trials 4 – 7 . Most clinical trials on newer therapeutic agents have been designed for cardiovascular outcome or mortality, with relatively small number of studies targeting renal outcomes as primary end-points 8 , 9 . Metformin, a biguanide derivative, is a preferred oral hypoglycemic agent (OHA) to manage T2DM.…”

Section: Introductionmentioning

confidence: 99%

Impact of metformin on cardiovascular and kidney outcome based on kidney function status in type 2 diabetic patients: a multicentric, retrospective cohort study

Yi,

Kwon,

Yun

et al. 2024

Sci Rep

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Metformin is the primary treatment for type 2 diabetes mellitus (T2DM) due to its effectiveness in improving clinical outcomes in patients with preserved renal function, however, the evidence on the effectiveness of metformin in various renal functions is lacking. We performed a retrospective, multicenter, observational study used data of patients with T2DM obtained from three tertiary hospitals’ databases. Patients given metformin within run-in periods and with at least one additional prescription formed the metformin cohort. A control cohort comprised those prescribed oral hypoglycemic agents other than metformin and never subsequently received a metformin prescription within observation period. For patients without diabetic nephropathy (DN), the outcomes included events of DN, major adverse cardiovascular events (MACE), and major adverse kidney events (MAKE). After 1:1 propensity matching, 1994 individuals each were selected for the metformin and control cohorts among T2DM patients without baseline DN. The incidence rate ratios (IRR) for DN, MACEs, and MAKEs between cohorts were 1.06 (95% CI 0.96–1.17), 0.76 (0.64–0.92), and 0.45 (0.33–0.62), respectively. In cohorts with renal function of CKD 3A, 3B, and 4, summarized IRRs of MACEs and MAKEs were 0.70 (0.57–0.87) and 0.39 (0.35–0.43) in CKD 3A, 0.83 (0.74–0.93) and 0.44 (0.40–0.48) in CKD 3B, and 0.71 (0.60–0.85) and 0.45 (0.39–0.51) in CKD 4. Our research indicates that metformin use in T2DM patients across various renal functions consistently correlates with a decreased risk of overt DN, MACE, and MAKE.

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“…Further, in ulcerative colitis patients, butyrate supplementation reduced activity of NF-κB [ 111 ] and in T2DM patients, it increased levels of GLP-1 [ 112 ]. GLP-1 reduces oxidative stress [ 113 ], improves glucose and insulin regulation [ 114 ] and has been shown to decrease intraglomerular pressure [ 114 ]. Interestingly, GLP-1 receptor agonists have been associated with gut microbiota changes, notably an expansion of Akkermansia muciniphila [ 55 ].…”

Section: Dietary Fibrementioning

confidence: 99%

Resistant Starch as a Dietary Intervention to Limit the Progression of Diabetic Kidney Disease

et al. 2022

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Diabetes is the leading cause of kidney disease, and as the number of individuals with diabetes increases there is a concomitant increase in the prevalence of diabetic kidney disease (DKD). Diabetes contributes to the development of DKD through a number of pathways, including inflammation, oxidative stress, and the gut-kidney axis, which may be amenable to dietary therapy. Resistant starch (RS) is a dietary fibre that alters the gut microbial consortium, leading to an increase in the microbial production of short chain fatty acids. Evidence from animal and human studies indicate that short chain fatty acids are able to attenuate inflammatory and oxidative stress pathways, which may mitigate the progression of DKD. In this review, we evaluate and summarise the evidence from both preclinical models of DKD and clinical trials that have utilised RS as a dietary therapy to limit the progression of DKD.

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A Review of the Renoprotective Effects of Novel Antidiabetic Agents

Cited by 6 publications

References 24 publications

Exercise-induced albuminuria increases over time in individuals with impaired glucose metabolism

Exercise-induced albuminuria increases over time in individuals with impaired glucose metabolism

Impact of metformin on cardiovascular and kidney outcome based on kidney function status in type 2 diabetic patients: a multicentric, retrospective cohort study

Resistant Starch as a Dietary Intervention to Limit the Progression of Diabetic Kidney Disease

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