Review

12 pages, 666 KiB

Open AccessReview

Vascular Calcification in Diabetic Kidney Disease

by Olivier Phan and Nobuhiko Joki

Kidney Dial. 2022, 2(4), 595-606; https://doi.org/10.3390/kidneydial2040054 - 01 Dec 2022

Viewed by 1728

The pathogenesis of vascular calcification (VC) in diabetes mellitus (DM) has not been completely elucidated. VC often occur in patients with DM and chronic kidney disease (CKD). The incidence of VC in diabetic patients is more frequent than in nondiabetic patients, which is [...] Read more.

The pathogenesis of vascular calcification (VC) in diabetes mellitus (DM) has not been completely elucidated. VC often occur in patients with DM and chronic kidney disease (CKD). The incidence of VC in diabetic patients is more frequent than in nondiabetic patients, which is an important cause of cardiovascular (CV) morbidity and mortality. VC is a progressive transformation of the vascular wall; it results from an active and complex phenomenon affecting particularly the vascular smooth muscle cells (VSMCs). It leads to a change in the phenotype of the VSMCs towards an osteoblastic-like phenotype. DM is associated with specific risk factors in addition to hyperglycemia, such as increased oxidative stress, proinflammatory state, hypertension, and chronic kidney disease (CKD) promoting endothelial dysfunction. This article provides an overview and update of the pathophysiological data on the role of DM in VC progression. Full article

(This article belongs to the Special Issue Diabetic Kidney Disease)

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12 pages, 303 KiB

Open AccessReview

Challenges in Management of Diabetic Patient on Dialysis

by Mohamed T. Eldehni, Lisa E. Crowley and Nicholas M. Selby

Kidney Dial. 2022, 2(4), 553-564; https://doi.org/10.3390/kidneydial2040050 - 31 Oct 2022

Viewed by 7538

Abstract

Diabetes mellitus is the leading cause of end-stage kidney disease in many countries. The management of diabetic patients who receive dialysis can be challenging. Diabetic dialysis patients have higher rates of cardiovascular events and mortality due to metabolic factors and accelerated vascular calcification. [...] Read more.

Diabetes mellitus is the leading cause of end-stage kidney disease in many countries. The management of diabetic patients who receive dialysis can be challenging. Diabetic dialysis patients have higher rates of cardiovascular events and mortality due to metabolic factors and accelerated vascular calcification. Diabetic haemodialysis patients have high rates of haemodynamic instability which leads to organ ischaemia and end organ damage; autonomic dysfunction seems to play an important role in haemodynamic instability and abnormal organ perfusion during haemodialysis. Poor glycaemic control contributes to fluid overload and worse cardiovascular outcome. Xerostomia and thirst are the main drivers for fluid overload in haemodialysis patients and in peritoneal dialysis a chronic state of hyperhydration that is related to absorption of glucose from the PD fluids, protein loss and malnutrition contributes to fluid overload. Glycaemic control is of great importance and adjustments to diabetic agents are required. In haemodialysis, a reduction in insulin dose is recommended to avoid hypoglycaemia whereas in peritoneal dialysis an increase in insulin dose is often required. Foot ulcers and infection are more common in diabetic dialysis patients compared to non-diabetic dialysis patients or diabetic patients with normal renal function and regular surveillance for early identification is important. Ultimately, a multi-disciplinary approach which includes diabetologist, nephrologist, dietitians, microbiologist, vascular surgeon, interventional radiologist is required to address the complicated aspects of diabetic patient care on dialysis. Full article

(This article belongs to the Special Issue Diabetic Kidney Disease)

15 pages, 961 KiB

Open AccessReview

What Nephrologists Should Know about the Use of Continuous Glucose Monitoring in Type 2 Diabetes Mellitus Patients on Chronic Hemodialysis

by Faiza Lamine, Menno Pruijm, Virginie Bahon and Anne Zanchi

Kidney Dial. 2022, 2(3), 459-473; https://doi.org/10.3390/kidneydial2030042 - 11 Aug 2022

Viewed by 4487

Abstract

Patients with type 2 diabetes (T2D) and end-stage kidney disease (ESKD) on renal replacement therapy represent a specific population with high morbidity and mortality, an increased risk of hypoglycemic episodes and large intra- and interdialysis glycemic variability. Antidiabetic treatment adjustment is therefore challenging, [...] Read more.

Patients with type 2 diabetes (T2D) and end-stage kidney disease (ESKD) on renal replacement therapy represent a specific population with high morbidity and mortality, an increased risk of hypoglycemic episodes and large intra- and interdialysis glycemic variability. Antidiabetic treatment adjustment is therefore challenging, especially in insulin-treated patients. Continuous glucose monitoring (CGM) is increasingly proposed to T2D patients on hemodialysis (HD), although data regarding flash monitoring systems (FMSs) and real-time CGM (rtCGM) in HD patients are limited. Small CGM pilot studies of a short duration demonstrated improvements in glycemic control and decreased hypoglycemic events, despite a lower accuracy of CGM as compared to capillary blood glucose. Moreover, CGM–drug interactions with vitamin C, mannitol and paracetamol can occur in HD diabetic patients and need further study. Despite these shortcomings, professional CGM has the potential to become an integral part of glucose monitoring of HD patients treated with insulin. Personal CGM prescriptions can especially be useful in highly selected, motivated T2D HD patients on multiple daily insulin injections or experiencing frequent hypoglycemia with preserved diabetes self-management abilities or in whom diabetes is fully managed by medical providers. A close collaboration between the clinical staff working on HD units and diabetology teams, and ongoing patient education, are mandatory for optimal use of CGM. Full article

(This article belongs to the Special Issue Diabetic Kidney Disease)

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10 pages, 278 KiB

Open AccessReview

The Epidemiology of Diabetic Kidney Disease

by Ellen K. Hoogeveen

Kidney Dial. 2022, 2(3), 433-442; https://doi.org/10.3390/kidneydial2030038 - 01 Aug 2022

Cited by 33 | Viewed by 14616

Abstract

Globally, the incidence and prevalence of diabetes mellitus has risen dramatically, owing mainly to the increase in type 2 diabetes mellitus (T2DM). In 2021, 537 million people worldwide (11% of the global population) had diabetes, and this number is expected to increase to [...] Read more.

Globally, the incidence and prevalence of diabetes mellitus has risen dramatically, owing mainly to the increase in type 2 diabetes mellitus (T2DM). In 2021, 537 million people worldwide (11% of the global population) had diabetes, and this number is expected to increase to 783 million (12%) by 2045. The growing burden of T2DM is secondary to the pandemic of obesity, which in turn has been attributed to increased intake of processed food, reduced physical activity, and increased sedentary behaviour. This so-called western lifestyle is related with the global increase in urbanization and technological development. One of the most frequent and severe long-term complications of diabetes is diabetic kidney disease (DKD), defined as chronic kidney disease in a person with diabetes. Approximately 20–50% of patients with T2DM will ultimately develop DKD. Worldwide, DKD is the leading cause of chronic kidney disease and end-stage kidney disease, accounting for 50% of cases. In addition, DKD results in high cardiovascular morbidity and mortality, and decreases patients’ health-related quality of life. In this review we provide an update of the diagnosis, epidemiology, and causes of DKD. Full article

(This article belongs to the Special Issue Diabetic Kidney Disease)

12 pages, 1292 KiB

Open AccessReview

Magnetic Resonance Imaging to Diagnose and Predict the Outcome of Diabetic Kidney Disease—Where Do We Stand?

by Menno Pruijm, Ibtisam Aslam, Bastien Milani, Wendy Brito, Michel Burnier, Nicholas M. Selby and Jean-Paul Vallée

Kidney Dial. 2022, 2(3), 407-418; https://doi.org/10.3390/kidneydial2030036 - 11 Jul 2022

Cited by 2 | Viewed by 4900

Abstract

Diabetic kidney disease (DKD) is a major public health problem and its incidence is rising. The disease course is unpredictable with classic biomarkers, and the search for new tools to predict adverse renal outcomes is ongoing. Renal magnetic resonance imaging (MRI) now enables [...] Read more.

Diabetic kidney disease (DKD) is a major public health problem and its incidence is rising. The disease course is unpredictable with classic biomarkers, and the search for new tools to predict adverse renal outcomes is ongoing. Renal magnetic resonance imaging (MRI) now enables the quantification of metabolic and microscopic properties of the kidneys such as single-kidney, cortical and medullary blood flow, and renal tissue oxygenation and fibrosis, without the use of contrast media. A rapidly increasing number of studies show that these techniques can identify early kidney damage in patients with DKD, and possibly predict renal outcome. This review provides an overview of the currently most frequently used techniques, a summary of the results of some recent studies, and our view on their potential applications, as well as the hurdles to be overcome for the integration of these techniques into the clinical care of patients with DKD. Full article

(This article belongs to the Special Issue Diabetic Kidney Disease)

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13 pages, 1163 KiB

Open AccessFeature PaperReview

GLP-1 Receptor Agonists in the Treatment of Patients with Type 2 Diabetes and Chronic Kidney Disease

by Joshua J. Neumiller, Radica Z. Alicic and Katherine R. Tuttle

Kidney Dial. 2022, 2(3), 386-398; https://doi.org/10.3390/kidneydial2030034 - 05 Jul 2022

Viewed by 4378

Abstract

Diabetic kidney disease (DKD) represents an important diabetes (DM) complication associated with significant impacts on morbidity, mortality, and quality of life. Recent evidence from cardiovascular and kidney outcome trials has dramatically impacted the standard of care for patients with DKD. While agents from [...] Read more.

Diabetic kidney disease (DKD) represents an important diabetes (DM) complication associated with significant impacts on morbidity, mortality, and quality of life. Recent evidence from cardiovascular and kidney outcome trials has dramatically impacted the standard of care for patients with DKD. While agents from the glucagon-like peptide-1 (GLP-1) receptor agonist class are known for their atherosclerotic cardiovascular disease (ASCVD) benefits, growing mechanistic and clinical evidence supports the benefit of GLP-1 receptor agonist therapy on progression of DKD. GLP-1 receptor activation is associated with anti-inflammatory and antifibrotic effects in the kidney, providing a plausible mechanism for kidney protection. Based on currently available clinical trial evidence, guidelines recommend the use of GLP-1 receptor agonists to mitigate ASCVD risk in patients with type 2 diabetes (T2D). Furthermore, based on secondary outcome data for kidney disease, GLP-1 receptor agonists are recommended as an option to mitigate kidney and ASCVD risk in patients with T2D and DKD who require intensification of glycemic control or for those who cannot take a sodium-glucose cotransporter-2 (SGLT2) inhibitor due to side effects or advanced stage DKD. Ongoing dedicated kidney disease outcome trials will further inform the role of GLP-1 receptor agonists in DKD management. This review discusses current considerations for GLP-1 receptor agonist use in patients with T2D and DKD. Full article

(This article belongs to the Special Issue Diabetic Kidney Disease)

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17 pages, 718 KiB

Open AccessReview

Cardiorenal Crosstalk in Patients with Heart Failure

by Sara Schukraft and Roger Hullin

Kidney Dial. 2022, 2(3), 369-385; https://doi.org/10.3390/kidneydial2030033 - 23 Jun 2022

Viewed by 2562

Abstract

Worsening renal function is associated with poor outcomes in heart failure and often accompanies the initiation and up-titration of guidelines-directed heart failure therapy. This narrative review summarizes current evidence on immediate and long-term effects of pharmacological or device-based treatment in heart failure patients [...] Read more.

Worsening renal function is associated with poor outcomes in heart failure and often accompanies the initiation and up-titration of guidelines-directed heart failure therapy. This narrative review summarizes current evidence on immediate and long-term effects of pharmacological or device-based treatment in heart failure patients with reduced or preserved left ventricular ejection fraction. Full article

(This article belongs to the Special Issue Diabetic Kidney Disease)

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20 pages, 910 KiB

Open AccessReview

The Pathophysiological Basis of Diabetic Kidney Protection by Inhibition of SGLT2 and SGLT1

by Yuji Oe and Volker Vallon

Kidney Dial. 2022, 2(2), 349-368; https://doi.org/10.3390/kidneydial2020032 - 18 Jun 2022

Cited by 4 | Viewed by 3426

Abstract

SGLT2 inhibitors can protect the kidneys of patients with and without type 2 diabetes mellitus and slow the progression towards end-stage kidney disease. Blocking tubular SGLT2 and spilling glucose into the urine, which triggers a metabolic counter-regulation similar to fasting, provides unique benefits, [...] Read more.

SGLT2 inhibitors can protect the kidneys of patients with and without type 2 diabetes mellitus and slow the progression towards end-stage kidney disease. Blocking tubular SGLT2 and spilling glucose into the urine, which triggers a metabolic counter-regulation similar to fasting, provides unique benefits, not only as an anti-hyperglycemic strategy. These include a low hypoglycemia risk and a shift from carbohydrate to lipid utilization and mild ketogenesis, thereby reducing body weight and providing an additional energy source. SGLT2 inhibitors counteract hyperreabsorption in the early proximal tubule, which acutely lowers glomerular pressure and filtration and thereby reduces the physical stress on the filtration barrier, the filtration of tubule-toxic compounds, and the oxygen demand for tubular reabsorption. This improves cortical oxygenation, which, together with lesser tubular gluco-toxicity and improved mitochondrial function and autophagy, can reduce pro-inflammatory, pro-senescence, and pro-fibrotic signaling and preserve tubular function and GFR in the long-term. By shifting transport downstream, SGLT2 inhibitors more equally distribute the transport burden along the nephron and may mimic systemic hypoxia to stimulate erythropoiesis, which improves oxygen delivery to the kidney and other organs. SGLT1 inhibition improves glucose homeostasis by delaying intestinal glucose absorption and by increasing the release of gastrointestinal incretins. Combined SGLT1 and SGLT2 inhibition has additive effects on renal glucose excretion and blood glucose control. SGLT1 in the macula densa senses luminal glucose, which affects glomerular hemodynamics and has implications for blood pressure control. More studies are needed to better define the therapeutic potential of SGLT1 inhibition to protect the kidney, alone or in combination with SGLT2 inhibition. Full article

(This article belongs to the Special Issue Diabetic Kidney Disease)

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20 pages, 1144 KiB

Open AccessReview

Role of Mineralocorticoid Receptor Antagonists in Diabetic Kidney Disease

by Maria-Eleni Alexandrou, Marieta P. Theodorakopoulou and Pantelis A. Sarafidis

Kidney Dial. 2022, 2(2), 163-182; https://doi.org/10.3390/kidneydial2020019 - 08 Apr 2022

Cited by 5 | Viewed by 4723

Abstract

Diabetic kidney disease (DKD) represents a major public health issue, currently posing an important burden on healthcare systems. Renin–angiotensin system (RAS) blockers are considered the cornerstone of treatment of albuminuric DKD. However, a high residual risk of progression to more advanced CKD stages [...] Read more.

Diabetic kidney disease (DKD) represents a major public health issue, currently posing an important burden on healthcare systems. Renin–angiotensin system (RAS) blockers are considered the cornerstone of treatment of albuminuric DKD. However, a high residual risk of progression to more advanced CKD stages under RAS blockade still remains, while relevant studies did not show significant declines in cardiovascular events with these agents in patients with DKD. Among several other pharmacological classes, mineralocorticoid receptor antagonists (MRAs) have received increasing interest, due to a growing body of high-quality evidence showing that spironolactone and eplerenone can significantly lower blood pressure and albuminuria in patients with CKD. Furthermore, finerenone, a novel nonsteroidal MRA with unique physicochemical properties, was shown to effectively reduce cardiovascular events and death, as well as the incidence of end-stage kidney disease in patients with type 2 diabetes. This review discusses previous and recent clinical evidence on the issue of nephroprotection and cardioprotection in DKD offered by mineralocorticoid receptor antagonism, aiming to aid clinicians in their treatment decisions for diabetic patients. Full article

(This article belongs to the Special Issue Diabetic Kidney Disease)

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