Kidney Disease in Type 2 Diabetes Mellitus and Benefits of Sodium-Glucose Cotransporter 2 Inhibitors: A Consensus Statement

Roy, Ajitesh; Maiti, Animesh; Sinha, Anirban; Baidya, Arjun; Basu, Avik; Sarkar, Dasarathi; Sanyal, Debmalya; Biswas, Dibakar; Maisnam, Indira; Pandit, Kaushik; Raychaudhuri, Moutusi; Sengupta, Nilanjan; Chakraborty, Partha Pratim; Mukhopadhyay, Pradip; Raychaudhuri, Pradip; Sahana, Pranab Kumar; Chatterjee, Pallab; Bhattacharjee, Rana; Dasgupta, Ranen; Saraogi, Ravi Kant; Pal, Sankar K.; Mukhopadhyay, Sibabrata; Mukhopadhyay, Satinath; Goswami, Soumik; Chowdhury, Subhankar; Ghosh, Sujoy

doi:10.1007/s13300-020-00921-y

Cited by 21 publications

(8 citation statements)

References 99 publications

(174 reference statements)

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“…Diabetes mellitus (DM) is a chronic metabolic disease with a rising incidence rate, and its microvascular and macrovascular complications are associated with a large global burden of morbidity and mortality [1]. Diabetic kidney disease (DKD) is a serious kidney-related complication that is present in approximately 40% of patients with DM [2], and patients with DKD have an increased risk of cardiovascular events and all-cause mortality [3]. Abnormal blood glucose status leads to oxidative stress and induces the release of inflammatory mediators, resulting in glomerular lesions in DM patients.…”

Section: Introductionmentioning

confidence: 99%

Administration of mesenchymal stem cells in diabetic kidney disease: a systematic review and meta-analysis

Lin

Yang

et al. 2021

Stem Cell Res Ther

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Background Mesenchymal stem cell (MSC) therapy shows great promise for diabetic kidney disease (DKD) patients. Research has been carried out on this topic in recent years. The main goals of this paper are to evaluate the therapeutic effects of MSCs on DKD through a meta-analysis and address the mechanism through a systematic review of the literature. Method An electronic search of the Embase, Cochrane Library, ISI Web of Science, PubMed, and US National Library of Medicine (NLM) databases was performed for all articles about MSC therapy for DKD, without species limitations, up to January 2020. Data were pooled for analysis with Stata SE 12. Result The MSC-treated group showed a large and statistically significant hypoglycemic effect at 1 week, 2 weeks, 3 weeks, 1 month, 2 months, 3 months, and 6 months. Total hypoglycemic effect was observed (SMD = − 1.954, 95%CI − 2.389 to − 1.519, p < 0.001; I2 = 85.1%). The overall effects on serum creatinine (SCr) and blood urea nitrogen (BUN) were analyzed, suggesting that MSC decreased SCr and BUN and mitigated the impairment of renal function (SCr: SMD = − 4.838, 95%CI − 6.789 to − 2.887, p < 0.001; I2 = 90.8%; BUN: SMD = − 4.912, 95%CI − 6.402 to − 3.422, p < 0.001; I2 = 89.3%). Furthermore, MSC therapy decreased the excretion of urinary albumin. Fibrosis indicators were assessed, and the results showed that transforming growth factor-β, collagen I, fibronectin, and α-smooth muscle actin were significantly decreased in the MSC-treated group compared to the control group. Conclusion MSCs might improve glycemic control and reduce SCr, BUN, and urinary protein. MSCs can also alleviate renal fibrosis. MSC therapy might be a potential treatment for DKD.

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Section: Introductionmentioning

confidence: 99%

Administration of mesenchymal stem cells in diabetic kidney disease: a systematic review and meta-analysis

Lin

Yang

et al. 2021

Stem Cell Res Ther

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“…T2DM induced changes such as impaired insulin signaling, hyperglycemia/glucotoxicity and lipotoxicity, are thought to contribute, along with hemodynamic changes, activation of the renin-angiotensin-aldosterone system (RAAS), endothelial dysfunction, inflammation and oxidative stress [6][7][8][9]. Indeed, approximately 20-40% of patients with T2D develop diabetic kidney disease, the most common cause of end stage renal failure [10].…”

Section: Introductionmentioning

confidence: 99%

The Goto Kakizaki rat: Impact of age upon changes in cardiac and renal structure, function

et al. 2021

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Background Patients with diabetes are at a high risk for developing cardiac dysfunction in the absence of coronary artery disease or hypertension, a condition known as diabetic cardiomyopathy. Contributing to heart failure is the presence of diabetic kidney disease. The Goto-Kakizaki (GK) rat is a non-obese, non-hypertensive model of type 2 diabetes that, like humans, shares a susceptibility locus on chromosome 10. Herein, we perform a detailed analysis of cardio-renal remodeling and response to renin angiotensin system blockade in GK rats to ascertain the validity of this model for further insights into disease pathogenesis. Methods Study 1: Male GK rats along with age matched Wistar control animals underwent longitudinal assessment of cardiac and renal function for 32 weeks (total age 48 weeks). Animals underwent regular echocardiography every 4 weeks and at sacrifice, early (~24 weeks) and late (~48 weeks) timepoints, along with pressure volume loop analysis. Histological and molecular characteristics were determined using standard techniques. Study 2: the effect of renin angiotensin system (RAS) blockade upon cardiac and renal function was assessed in GK rats. Finally, proteomic studies were conducted in vivo and in vitro to identify novel pathways involved in remodeling responses. Results GK rats developed hyperglycaemia by 12 weeks of age (p<0.01 c/w Wistar controls). Echocardiographic assessment of cardiac function demonstrated preserved systolic function by 48 weeks of age. Invasive studies demonstrated left ventricular hypertrophy, pulmonary congestion and impaired diastolic function. Renal function was preserved with evidence of hyperfiltration. Cardiac histological analysis demonstrated myocyte hypertrophy (p<0.05) with evidence of significant interstitial fibrosis (p<0.05). RT qPCR demonstrated activation of the fetal gene program, consistent with cellular hypertrophy. RAS blockade resulted in a reduction blood pressure(P<0.05) cardiac interstitial fibrosis (p<0.05) and activation of fetal gene program. No significant change on either systolic or diastolic function was observed, along with minimal impact upon renal structure or function. Proteomic studies demonstrated significant changes in proteins involved in oxidative phosp4horylation, mitochondrial dysfunction, beta-oxidation, and PI3K/Akt signalling (all p<0.05). Further, similar changes were observed in both LV samples from GK rats and H9C2 cells incubated in high glucose media. Conclusion By 48 weeks of age, the diabetic GK rat demonstrates evidence of preserved systolic function and impaired relaxation, along with cardiac hypertrophy, in the presence of hyperfiltration and elevated protein excretion. These findings suggest the GK rat demonstrates some, but not all features of diabetes induced “cardiorenal” syndrome. This has implications for the use of this model to assess preclinical strategies to treat cardiorenal disease.

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“…37,38 In the past, cardiovascular outcome trials in Table 3 have demonstrated the efficacy of SGLT2i (empagliflozin [EMPA-REG OUTCOME], canagliflozin [CANVAS], and dapagliflozin [DECLARE-TIMI 58]) in slowing CKD progression and reducing hyperglycaemia in patients with type 2 diabetes mellitus (T2DM). [39][40][41][42][43][44][45][46][47][48] However, these are largely secondary outcomes, and the mean eGFR inclusion criteria was >60 ml/min/1.73m 2 . Recently, a meta-analysis study by Zhao evaluated the potential benefits of a combination of SGLT2i and ACEI/ARB over ACEI/ARB plus placebo in lowering cardiorenal events in patients with T2DM.…”

Section: Chronic Kidney Disease and Sodium-glucose Cotransporter 2 In...mentioning

confidence: 99%

“…51 Table 3: Key highlights of the SGLT2i cardiovascular outcomes trials (CVOTs). Adapted data from: Mahaffey et al 2019, 39 Wiviott et al 2019, 40 Roy et al 2020, 41 Zinman et al 2015, 42 Rangaswami et al 2020, 43 McMurray et al 2019, 44 Packer et al 2020, 45 Anker et al 2021, 46 Perkovic et al 2019, 47 Heerspink et al 2020. Table 4: A) Key highlights of CREDENCE and DAPA-CKD trials.…”

Section: Chronic Kidney Disease and Sodium-glucose Cotransporter 2 In...mentioning

confidence: 99%

Complications of Chronic Kidney Disease: Therapeutic Approaches and What Can Be Done to Halt Disease Progression?

Khan¹

2022

SFP

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Singapore is one of the most rapidly ageing societies in the world. Currently, Singapore ranks first in the world for the incidence of diabetes-induced end-stage renal disease (ESRD) and seventh for the incidence of kidney failures per million population. It is estimated that nearly one-quarter of Singapore’s population will have chronic kidney disease (CKD) by 2035. Disease management of CKD has been identified as a critical issue due to the rapid increase in cases among the elderly in recent years. Chronic kidney disease is associated with adverse clinical outcomes, and metabolic complications such as anaemia, cardiovascular events, and CKD-associated metabolic bone diseases present treatment management complexities to healthcare professionals. Early detection and management of CKD can avert complications before symptoms occur and prevent the progressive loss of kidney function over time. Angiotensin-converting enzyme inhibitors (ACEI) or angiotensin receptor blockers (ARBs) are recommended for hypertension and proteinuria management in CKD patients with and without diabetes. However, neither of these agents alone reduces the risk of all-cause mortality; furthermore, combinational therapy of ACEI plus ARB is associated with renal dysfunction, stroke, and/or hyperkalaemia. Recently, the use of sodium–glucose cotransporter 2 inhibitors (SGLT2i) has been shown to provide favourable effects on the kidney and cardiovascular outcomes in patients with or without type 2 diabetes mellitus. Studies have shown that early initiation of SGLT2i may slow or halt the progression of CKD in patients with the risk of CKD and ESRD. This review discusses the mechanisms underlying the progression of CKD, its associated risk factors and summarises the management strategies as per Kidney Disease Outcomes Quality Initiative clinical practice guideline recommendations. This article also summarises the evidence regarding the use of SGLT2i in slowing the progression of CKD and improvement of health-related quality of life.

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Kidney Disease in Type 2 Diabetes Mellitus and Benefits of Sodium-Glucose Cotransporter 2 Inhibitors: A Consensus Statement

Cited by 21 publications

References 99 publications

Administration of mesenchymal stem cells in diabetic kidney disease: a systematic review and meta-analysis

Administration of mesenchymal stem cells in diabetic kidney disease: a systematic review and meta-analysis

The Goto Kakizaki rat: Impact of age upon changes in cardiac and renal structure, function

Complications of Chronic Kidney Disease: Therapeutic Approaches and What Can Be Done to Halt Disease Progression?

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