scholarly journals Mineralocorticoid Receptor Antagonists in Diabetic Kidney Disease

2021 ◽  
Vol 14 (6) ◽  
pp. 561
Author(s):  
Nina Vodošek Vodošek Hojs ◽  
Sebastjan Bevc ◽  
Robert Ekart ◽  
Nejc Piko ◽  
Tadej Petreski ◽  
...  

Diabetes mellitus is a global health issue and main cause of chronic kidney disease. Both diseases are also linked through high cardiovascular morbidity and mortality. Diabetic kidney disease (DKD) is present in up to 40% of diabetic patients; therefore, prevention and treatment of DKD are of utmost importance. Much research has been dedicated to the optimization of DKD treatment. In the last few years, mineralocorticoid receptor antagonists (MRA) have experienced a renaissance in this field with the development of non-steroidal MRA. Steroidal MRA have known cardiorenal benefits, but their use is limited by side effects, especially hyperkalemia. Non-steroidal MRA still block the damaging effects of mineralocorticoid receptor overactivation (extracellular fluid volume expansion, inflammation, fibrosis), but with fewer side effects (hormonal, hyperkalemia) than steroidal MRA. This review article summarizes the current knowledge and newer research conducted on MRA in DKD.

Author(s):  
Alberto Ortiz ◽  
Charles J Ferro ◽  
Olga Balafa ◽  
Michel Burnier ◽  
Robert Ekart ◽  
...  

Abstract Diabetic kidney disease develops in about 40% of patients with diabetes and is the commonest cause of chronic kidney disease worldwide. Patients with chronic kidney disease, especially those with diabetes mellitus, are at high risk of both developing kidney failure and cardiovascular death. The use of renin-angiotensin system blockers to reduce the incidence of kidney failure in patients with diabetic kidney disease dates back to studies that are now 20 or more years old. During the last few years sodium-glucose co-transporter-2 inhibitors have shown beneficial renal effects in randomized trials. However, even in response to combined treatment with renin-angiotensin system blockers and sodium-glucose co-transporter-2 inhibitors, the renal residual risk remains high with kidney failure only deferred, but not avoided. The risk of cardiovascular death also remains high even with optimal current treatment. Steroidal mineralocorticoid receptor antagonists reduce albuminuria and surrogate markers of cardiovascular disease in patients already on optimal therapy. However, their use has been curtailed by the significant risk of hyperkalaemia. In The FInerenone in reducing kiDnEy faiLure and dIsease prOgression in Diabetic Kidney Disease (FIDELIO-DKD) study comparing the actions of the non-steroidal mineralocorticoid receptor antagonist finerenone with placebo, finerenone reduced the progression of diabetic kidney disease and the incidence of cardiovascular events with a relatively safe adverse event profile. This document presents in detail the available evidence on the cardioprotective and nephroprotective effects of mineralocorticoid receptor antagonists, analyses the potential mechanisms involved and discusses their potential future place in the treatment of patients with diabetic chronic kidney disease.


2021 ◽  
Vol 12 ◽  
Author(s):  
Daiji Kawanami ◽  
Yuichi Takashi ◽  
Yoshimi Muta ◽  
Naoki Oda ◽  
Dai Nagata ◽  
...  

Diabetic kidney disease (DKD) is a major cause of end-stage kidney disease (ESKD) worldwide. Mineralocorticoid receptor (MR) plays an important role in the development of DKD. A series of preclinical studies revealed that MR is overactivated under diabetic conditions, resulting in promoting inflammatory and fibrotic process in the kidney. Clinical studies demonstrated the usefulness of MR antagonists (MRAs), such as spironolactone and eplerenone, on DKD. However, concerns regarding their selectivity for MR and hyperkalemia have remained for these steroidal MRAs. Recently, nonsteroidal MRAs, including finerenone, have been developed. These agents are highly selective and have potent anti-inflammatory and anti-fibrotic properties with a low risk of hyperkalemia. We herein review the current knowledge and future perspectives of MRAs in DKD treatment.


Diabetes ◽  
2019 ◽  
Vol 68 (Supplement 1) ◽  
pp. 539-P
Author(s):  
YOSHINORI KAKUTANI ◽  
MASANORI EMOTO ◽  
KATSUHITO MORI ◽  
YUKO YAMAZAKI ◽  
AKINOBU OCHI ◽  
...  

Hypertension ◽  
2021 ◽  
Vol 77 (5) ◽  
pp. 1442-1455
Author(s):  
Pantelis Sarafidis ◽  
Christodoulos E. Papadopoulos ◽  
Vasilios Kamperidis ◽  
George Giannakoulas ◽  
Michael Doumas

Chronic kidney disease (CKD) and cardiovascular disease are intimately linked. They share major risk factors, including age, hypertension, and diabetes, and common pathogenetic mechanisms. Furthermore, reduced renal function and kidney injury documented with albuminuria are independent risk factors for cardiovascular events and mortality. In major renal outcome trials and subsequent meta-analyses in patients with CKD, ACE (angiotensin-converting enzyme) inhibitors and ARBs (angiotensin II receptor blockers) were shown to effectively retard CKD progression but not to significantly reduce cardiovascular events or mortality. Thus, a high residual risk for cardiovascular disease progression under standard-of-care treatment is still present for patients with CKD. In contrast to the above, several outcome trials with SGLT-2 (sodium-glucose cotransporter-2) inhibitors and MRAs (mineralocorticoid receptor antagonists) clearly suggest that these agents, apart from nephroprotection, offer important cardioprotection in this population. This article discusses existing evidence on the effects of SGLT-2 inhibitors and MRAs on cardiovascular outcomes in patients with CKD that open new roads in cardiovascular protection of this heavily burdened population.


2021 ◽  
Vol 36 (Supplement_1) ◽  
Author(s):  
Liliana Garneata ◽  
Carmen-Antonia Mocanu ◽  
Tudor Petrisor Simionescu ◽  
Andreea Elena Mocanu ◽  
Gabriel Mircescu

Abstract Background and Aims Dietary protein restriction is rediscussed as mainstay approach in advanced Chronic Kidney Disease (CKD), both in diabetics and non-diabetics to defer renal replacement therapy (RRT), mainly by better metabolic control; improvements in mineral bone disorders (MBD) were also suggested, but less studied in Diabetic Kidney Disease (DKD). An unicentric prospective interventional trial aimed to assess the effects of ketoanalogue-supplemented low protein diet (sLPD) on proteinuria and CKD progression (data already presented). The parameters of MBD were also evaluated. Method Adult diabetic patients (452) with stable CKD stage 4+, proteinuria>3g/g creatininuria and SGA A were enrolled in a run-in phase (3 mo), with LPD (0.6g/kg dry ideal bw). Those who proved adherent (92, 64% males, median age 55.7 yrs, 65% on insulin) received sLPD (Ketosteril®, 1 tablet/10kg) for 12mo. Monitoring and treatment followed the Best Practice Guidelines. The primary endpoint was proteinuria during intervention as compared to pre-enrolment. Serum levels of calcium, phosphates and iPTH were considered to assess MBD. Nutrition, inflammation (SGA, BMI, serum albumin, CRP) and compliance were safety parameters. Results In patients with advanced DKD and severe proteinuria, sLPD was associated with a 69 (63; 82) % reduction in proteinuria (data presented). Significant amelioration in MBD was noted: serum levels of calcium and phosphates were significantly ameliorated at the end of the study as compared to enrolment - 4.3 (4.2-4.9) vs 3.2 (3.1-3.5) mg/dL and 5.4 (4.9-6.1) vs 8.2 (7.8-8.9) mg/dL, respectively. Serum iPTH significantly decreased: 185 (168-212) vs 375 (354-585) pg/mL. The need for calcium supplementation decreased: 6.5 (6.0-6.7) vs 7.0 (6.8-7.3) g/day. Vitamin D was required by only 35% vs 65% of patients. Nutritional status was preserved and dietary compliance was very good throughout the study. Conclusion In patients with advanced DKD ketoanalogue supplemented low protein diet seems to be effective and safe as part of MBD management.


2021 ◽  
Vol 8 (2) ◽  
pp. 112-119
Author(s):  
Juju Raj Shrestha ◽  
Kashyap Dahal ◽  
Anil Baral ◽  
Rajani Hada

Introduction: Non diabetic kidney disease (NDKD), a treatable condition, is common in diabetic patients with atypical clinical presentations. Present study aimed to find out histopathological diagnosis of kidney disease in type 2 Diabetes mellitus with such presentations. Method: This was a hospital based cross sectional study conducted in Nephrology department, Bir hospital, Nepal from Aug 2019 to January 2021. Total 29 diabetic patients with atypical presentations, rapid rise of proteinuria alone (n=5), with microscopic hematuria (n=6), with impaired renal function (n=8) and rapid rise of creatinine with (n=8) or without (n=2) microscopic hematuria were included. The baseline information was recorded and kidney biopsy was performed. Result: The mean age of patients was 52.6±10.4 y and 22(75.9%) were male. Diabetic retinopathy (DR) was absent in 24(82.8%) patients. Presence of NDKD alone was in 6(20.7%) and superimposed on diabetic kidney disease (DKD) in 10(34.5%) with total NDKD in 16(55.2%) and isolated DKD in 13(44.8%) patients. Non diabetic kidney disease were glomerulonephritis 12(75%) with membranous nephropathy 4(25%) and IgA nephropathy 4(25%) patients. The significant difference between NDKD and isolated DKD was only the duration of diabetes < 5 y in 8(61.5%) of isolated DKD and ≥5 y in 13(81.2%) patients with NDKD (p=0.018). Diabetic retinopathy was absent in 6(100%) patients with isolated NDKD, 8(80%) of class III and 5(62.5%) of class IV DKD. Conclusion: Glomerulonephritis is the commonest NDKD in type 2 DM with atypical presentation and advance DKD (Class III & IV) is present even in absence of diabetic retinopathy and short duration of diabetes.


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