scholarly journals Management of hypertension and renin-angiotensin-aldosterone system blockade in adults with diabetic kidney disease: Association of British Clinical Diabetologists and the Renal Association UK guideline update 2021

2022 ◽  
Vol 23 (1) ◽  
Author(s):  
D. Banerjee ◽  
P. Winocour ◽  
T. A. Chowdhury ◽  
P. De ◽  
M. Wahba ◽  
...  

AbstractPeople with type 1 and type 2 diabetes are at risk of developing progressive chronic kidney disease (CKD) and end-stage kidney failure. Hypertension is a major, reversible risk factor in people with diabetes for development of albuminuria, impaired kidney function, end-stage kidney disease and cardiovascular disease. Blood pressure control has been shown to be beneficial in people with diabetes in slowing progression of kidney disease and reducing cardiovascular events. However, randomised controlled trial evidence differs in type 1 and type 2 diabetes and different stages of CKD in terms of target blood pressure. Activation of the renin-angiotensin-aldosterone system (RAAS) is an important mechanism for the development and progression of CKD and cardiovascular disease. Randomised trials demonstrate that RAAS blockade is effective in preventing/ slowing progression of CKD and reducing cardiovascular events in people with type 1 and type 2 diabetes, albeit differently according to the stage of CKD. Emerging therapy with sodium glucose cotransporter-2 (SGLT-2) inhibitors, non-steroidal selective mineralocorticoid antagonists and endothelin-A receptor antagonists have been shown in randomised trials to lower blood pressure and further reduce the risk of progression of CKD and cardiovascular disease in people with type 2 diabetes. This guideline reviews the current evidence and makes recommendations about blood pressure control and the use of RAAS-blocking agents in different stages of CKD in people with both type 1 and type 2 diabetes.

2018 ◽  
Vol 209 (10) ◽  
pp. 440-446 ◽  
Author(s):  
Wai H Lim ◽  
David W Johnson ◽  
Carmel Hawley ◽  
Charmaine Lok ◽  
Kevan R Polkinghorne ◽  
...  

2020 ◽  
Vol 19 (1) ◽  
Author(s):  
Elvira D’Andrea ◽  
Aaron S. Kesselheim ◽  
Jessica M. Franklin ◽  
Emily H. Jung ◽  
Spencer Phillips Hey ◽  
...  

Abstract Background We explored whether clinically relevant baseline characteristics of patients with type 2 diabetes can modify the effect of glucagon-like peptide-1 receptor agonists (GLP-1 RA) or sodium-glucose cotransporter-2 inhibitors (SGLT-2i) on the risk of major adverse cardiovascular events (MACE). Methods We investigated Medline and EMBASE through June 2019. We included randomized clinical trials reporting the effect of GLP-1 RA or SGLT-2i on MACE in subgroups of patients with type 2 diabetes, identified through key baseline factors: established cardiovascular disease; heart failure; chronic kidney disease; uncontrolled diabetes; duration of diabetes; hypertension; obesity; age; gender and race. Hazard ratios (HRs) and 95% confidence intervals (CIs) from trials were meta-analyzed using random-effects models. Results Ten trials enrolling 89,790 patients were included in the analyses. Subgroup meta-analyses showed a 14% risk reduction of MACE in patients with established cardiovascular disease [GLP1-RA: HR, 0.86 (95% CI, 0.80–0.93); SGLT-2i: 0.86 (0.80–0.93)], and no effect in at-risk patients without history of cardiovascular events [GLP1-RA: 0.94 (0.82–1.07); SGLT-2i: 1.00 (0.87–1.16)]. We observed a trend toward larger treatment benefits with SGLT-2i among patients with chronic kidney disease [0.82 (0.69–0.97)], and patients with uncontrolled diabetes for both GLP1-RA or SGLT-2i [GLP1-RA: 0.82 (0.71–0.95); SGLT-2i: 0.84 (0.75–0.95)]. Uncontrolled hypertension, obesity, gender, age and race did not appear to modify the effect of these drugs. Conclusions In this exploratory analysis, history of cardiovascular disease appeared to modify the treatment effect of SGLT2i or GLP1-RA on MACE. Chronic kidney disease and uncontrolled diabetes should be further investigated as potential effect modifiers.


2020 ◽  
pp. 4975-4987
Author(s):  
Rudolf Bilous

Diabetic nephropathy is the commonest cause of endstage renal disease in the developed world. Aetiology and pathology—causation is related to glycaemic control, hypertension, inflammation, genetic factors, and dietary and other environmental factors. Pathological hallmarks in the glomerulus are thickening of the glomerular basement membrane and mesangial expansion, with or without nodule formation, secondary to an accumulation of extracellular matrix. Many patients have a varying severity of tubulointerstitial inflammation and fibrosis. Staging and natural history—is classically described in terms of urinary albumin excretion rate (UAER). Clinical features—most patients (>60%) will have a normal UAER throughout their diabetic life, but 1 to 2% of the remainder develop persistent moderately increased albuminuria each year. Once UAER exceeds 200 µg/min, there tends to be a relentless increase in proteinuria and glomerular filtration rate declines progressively at a rate that largely depends upon blood pressure control. Prevention—tight glycaemic control can prevent moderately increased albuminuria in both type 1 and type 2 diabetes. Whether intensive blood pressure control using angiotensin-converting enzyme (ACE) inhibitors can also prevent this remains controversial. In both type 1 and type 2 diabetes, intensive blood pressure control using ACE inhibitors or angiotensin II receptor blockers (ARBs) slows progression from moderately to severely increased albuminuria and also slows the rate of decline in glomerular filtration rate in those with severely increased albuminuria. Management—aims for (1) control of glycaemia, (2) control of hypertension (<130/80 mmHg) using an ACE inhibitor or an ARB as first line; and (3) other interventions, including some or all of serum lipid lowering, smoking cessation, and reduction of dietary protein and salt.


2020 ◽  
Author(s):  
Elvira D'Andrea ◽  
Aaron S. Kesselheim ◽  
Jessica M. Franklin ◽  
Emily Jung ◽  
Spencer Phillips Hey ◽  
...  

Abstract Background We explored whether clinically relevant baseline characteristics of patients with type 2 diabetes can modify the effect of glucagon-like peptide-1 receptor agonists (GLP-1 RA) or sodium-glucose cotransporter-2 inhibitors (SGLT-2i) on the risk of major adverse cardiovascular events (MACE). Methods We investigated Medline and EMBASE through June 2019. We included randomized clinical trials reporting the effect of GLP-1 RA or SGLT-2i on MACE in subgroups of patients with type 2 diabetes, identified through key baseline factors: established cardiovascular disease; heart failure; chronic kidney disease; uncontrolled diabetes; duration of diabetes; hypertension; obesity; age; gender and race. Hazard ratios (HRs) and 95% confidence intervals (CIs) from trials were meta-analyzed using random-effects models. Results Nine trials enrolling 87,143 patients were included in the analyses. Subgroup meta-analyses showed a 14% risk reduction of MACE in patients with established cardiovascular disease [GLP1-RA: HR, 0.86 (95% CI, 0.79–0.94); SGLT-2i: 0.86 (0.80–0.93)], and no effect in at-risk patients without history of cardiovascular events [GLP1-RA: 0.95 (0.83–1.08); SGLT-2i: 1.00 (0.87–1.16)]. We observed a trend toward larger treatment benefits with SGLT-2i among patients with chronic kidney disease [0.82 (0.69–0.97)], and patients with uncontrolled diabetes for both GLP1-RA or SGLT-2i [GLP1-RA: 0.82 (0.71–0.95); SGLT-2i: 0.84 (0.75–0.95)]. Uncontrolled hypertension, obesity, gender, age and race did not appear to modify the effect of these drugs. Conclusions In this exploratory analysis, history of cardiovascular disease appeared to modify the treatment effect of SGLT2i or GLP1-RA on MACE. Chronic kidney disease and uncontrolled diabetes should be further investigated as potential effect modifiers.


2019 ◽  
Vol 22 (4) ◽  
pp. 178
Author(s):  
Piscitelli, P.

Diabetic patients have a high risk to develop diabetic nephropathy. Diabetic nephropathy represents non only a risk factor for progression toward end stage renal disease but it is also associates with an increased risk to have of major cardiovascular events. Over the last few years, analysis of the AMD annals dataset has contributed several important insights on the clinical features of type 2 diabetes kidney disease and their prognostic and therapeutic implications. First, non-albuminuric renal impairment is the predominant clinical phenotype. Even though associated with a lower risk of progression compared to overt albuminuria, it contributes significantly to the burden of end-stage renaldisease morbidity. Second, optimal blood pressure control provides significant but incomplete renal protection. It reduces albuminuria but there may be a J curve phenomenon with eGFR at very low blood pressure values. Third, hyperuricemia and diabetic hyperlipidemia, namely elevated triglycerides and low HDL cholesterol, are strong independent predictorsof chronic kidney disease onset in diabetes, although the pathogenetic mechanisms underlying these associationsremain uncertain. These data help clarify the natural history of CKD in patients with type 2 diabetes and provide important clues for designing futureinterventional studies. KEY WORDS albuminuria; glomerular filtration rate; hypertension; uric acid; type2 diabetes mellitus.


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