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Editorial Board Members’ Collection Series: Chronic Kidney Disease in Diabetes

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A special issue of Journal of Clinical Medicine (ISSN 2077-0383). This special issue belongs to the section "Nephrology & Urology".

Deadline for manuscript submissions: closed (15 September 2023) | Viewed by 34227

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Special Issue Editors

Prof. Dr. Radica Alicic

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Guest Editor

Providence Medical Research Center, Providence Health Care, Spokane, WA, USA
Interests: diabetic kidney disease; diabetes management in diabetic kidney disease; diabetes management in hospitalized patients with diabetic kidney disease; sodium glucose co-transporter 2 inhibitors (SGLT-2) and chronic kidney disease; glucagon-like peptide receptor agonists (GLP-1 receptor agonists); chronic kidney disease

Dr. Christos Argyropoulos

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Guest Editor

Department of Internal Medicine, University of New Mexico School of Medicine, 901 University Blvd SE, Suite 150, Albuquerque, NM 87106, USA
Interests: diabetes; diabetic nephropathy; RNA biomarkers; epidemiology; statistics; big data

Special Issue Information

Dear Colleagues,

Chronic kidney disease (CKD) due to diabetes without other known causes, also referred to as diabetic kidney disease (DKD) , develops in approximately 40% of patients with type 2 diabetes and 30% of those with type 1 diabetes. The worldwide epidemic of diabetes has established DKD as the leading cause of kidney failure globally. The majority of patients who develop this microvascular complication die prematurely from cardiovascular disease, and only a minority progresses to kidney failure requiring kidney replacement therapy. Recent large clinical trials of sodium glucose cotransporter 2 inhibitors, incretin therapies (glucagon like peptide inhibitor-1 receptor agonists, and gastric inhibitory polypeptide), and non-steroidal mineralocorticoid receptor antagonist have demonstrated a reduction in the risk of progression of kidney disease and associated cardiovascular risk. After decades of limited therapeutic options with sizable residual risk, new classes of medications promise to transform care and the lives of DKD patients. Considering the steady increase in the numbers of cases of DKD, efforts to raise awareness of the large burden of disease and increased risk of dying, improve recognition, and implement effective management of DKD are critical.

This Special issue will provide a concise overview of epidemiology, putative mechanisms involved in development and progression of DKD, and a review of current professional guidelines for early recognition and management.

Prof. Dr. Radica Alicic
Dr. Christos Argyropoulos
Guest Editors

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Keywords

diabetic kidney disease
pathogenesis
epidemiology
diagnosis
management
cardiovascular risk
sodium–glucose cotransporter-2 inhibitors
glucagon-like peptide-1 receptor agonists
mineralocorticoid receptor antagonists
gas-tric inhibitory polypeptide
implementation

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Published Papers (10 papers)

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Research

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10 pages, 1072 KiB

Open AccessArticle

The Uricosuric Effect of SGLT2 Inhibitors Is Maintained in the Long Term in Patients with Chronic Kidney Disease and Type 2 Diabetes Mellitus

by Paula Sánchez-Briales, María Marques Vidas, Paula López-Sánchez, María Victoria López-Illázquez, Lucía Martín-Testillano, Aylin Vedat-Ali and Jose Portolés

J. Clin. Med. 2024, 13(5), 1360; https://doi.org/10.3390/jcm13051360 - 27 Feb 2024

Cited by 1 | Viewed by 1326

Abstract

(1) Background: Sodium–glucose co-transporter 2 inhibitors (SGLT2is) increase uric acid excretion. The intensity of uricosuria is linked to glycosuria. (2) Methods: We aim to analyze the effect of SGLT2 inhibitors on urinary fractional excretion (FE) of uric acid and glucose in patients with type 2 diabetes mellitus (T2DM) and chronic kidney disease (CKD) in a single-center retrospective study with patients with T2DM and CKD who started on treatment with SGLT2is. Patients on renal replacement therapy or with glucagon-like peptide-1 (GLP1) analogs were excluded. Subgroup analysis was performed according to the estimated glomerular filtration rate (eGFR), the SGLT2i molecule, the main comorbidities, and concomitant treatment. As a secondary objective, the study analyzed the effect of SGLT2 inhibitors on uricemia levels. (3) Results: Seventy-three patients were analyzed, with a mean follow-up of 1.2 years. Uric acid and glucose FE significantly increased after the initiation of SGLT2is. This increase remained stable during the follow-up without differences among eGFR groups. No significant reduction in uricemia was observed. However, a trend towards a decrease was observed. (4) Conclusion: The use of SGLT2is in patients with CKD and T2DM is associated with an increase in uric acid FE, which maintains stability irrespective of glomerular filtration loss at least during 24 months of follow-up. Full article

(This article belongs to the Special Issue Editorial Board Members’ Collection Series: Chronic Kidney Disease in Diabetes)

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9 pages, 841 KiB

Open AccessArticle

Canagliflozin Attenuates PromarkerD Diabetic Kidney Disease Risk Prediction Scores

by Kirsten E. Peters, Scott D. Bringans, Ronan S. O’Neill, Tasha S. C. Lumbantobing, James K. C. Lui, Timothy M. E. Davis, Michael K. Hansen and Richard J. Lipscombe

J. Clin. Med. 2023, 12(9), 3247; https://doi.org/10.3390/jcm12093247 - 1 May 2023

Cited by 1 | Viewed by 1601

Abstract

PromarkerD is a biomarker-based blood test that predicts kidney function decline in people with type 2 diabetes (T2D) who may otherwise be missed by current standard of care tests. This study examined the association between canagliflozin and change in PromarkerD score (Δ score) over a three-year period in T2D participants in the CANagliflozin cardioVascular Assessment Study (CANVAS). PromarkerD scores were measured at baseline and Year 3 in 2008 participants with preserved kidney function (baseline eGFR ≥60 mL/min/1.73 m²). Generalized estimating equations were used to assess the effect of canagliflozin versus placebo on PromarkerD scores. At baseline, the participants (mean age 62 years, 32% females) had a median PromarkerD score of 3.9%, with 67% of participants categorized as low risk, 14% as moderate risk, and 19% as high risk for kidney function decline. After accounting for the known acute drop in eGFR following canagliflozin initiation, there was a significant treatment-by-time interaction (p < 0.001), whereby participants on canagliflozin had decreased mean PromarkerD scores from baseline to Year 3 (Δ score: −1.0% [95% CI: −1.9%, −0.1%]; p = 0.039), while the scores of those on placebo increased over the three-year period (Δ score: 6.4% [4.9%, 7.8%]; p < 0.001). When stratified into PromarkerD risk categories, participants with high risk scores at baseline who were randomized to canagliflozin had significantly lower scores at Year 3 (Δ score: −5.6% [−8.6%, −2.5%]; p < 0.001), while those on placebo retained high scores (Δ score: 4.5% [0.3%, 8.8%]; p = 0.035). This post hoc analysis of data from CANVAS showed that canagliflozin significantly lowered PromarkerD risk scores, with the effect greatest in those T2D participants who were classified at study entry as at high risk of a subsequent decline in kidney function. Full article

(This article belongs to the Special Issue Editorial Board Members’ Collection Series: Chronic Kidney Disease in Diabetes)

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Review

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20 pages, 2312 KiB

Open AccessReview

Type 2 Diabetes and Chronic Kidney Disease: An Opportunity for Pharmacists to Improve Outcomes

by Joshua J. Neumiller, Wendy L. St. Peter and Jay H. Shubrook

J. Clin. Med. 2024, 13(5), 1367; https://doi.org/10.3390/jcm13051367 - 28 Feb 2024

Viewed by 2341

Abstract

Chronic kidney disease (CKD) is an important contributor to end-stage kidney disease, cardiovascular disease, and death in people with type 2 diabetes (T2D), but current evidence suggests that diagnosis and treatment are often not optimized. This review examines gaps in care for patients with CKD and how pharmacist interventions can mitigate these gaps. We conducted a PubMed search for published articles reporting on real-world CKD management practice and compared the findings with current recommendations. We find that adherence to guidelines on screening for CKD in patients with T2D is poor with particularly low rates of testing for albuminuria. When CKD is diagnosed, the prescription of recommended heart–kidney protective therapies is underutilized, possibly due to issues around treatment complexity and safety concerns. Cost and access are barriers to the prescription of newer therapies and treatment is dependent on racial, ethnic, and socioeconomic factors. Rates of nephrologist referrals for difficult cases are low in part due to limitations of information and communication between specialties. We believe that pharmacists can play a vital role in improving outcomes for patients with CKD and T2D and support the cost-effective use of healthcare resources through the provision of comprehensive medication management as part of a multidisciplinary team. The Advancing Kidney Health through Optimal Medication Management initiative supports the involvement of pharmacists across healthcare systems to ensure that comprehensive medication management can be optimally implemented. Full article

(This article belongs to the Special Issue Editorial Board Members’ Collection Series: Chronic Kidney Disease in Diabetes)

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18 pages, 465 KiB

Open AccessReview

Diabetic Kidney Disease in Post-Kidney Transplant Patients

by Ngoc-Yen T. Pham, Diego Cruz, Luis Madera-Marin, Raja Ravender and Pablo Garcia

J. Clin. Med. 2024, 13(3), 793; https://doi.org/10.3390/jcm13030793 - 30 Jan 2024

Cited by 2 | Viewed by 3077

Abstract

Post-transplant diabetes mellitus (PTDM) is a common occurrence in post-kidney transplantation and is associated with greater mortality, allograft failure, and increased risk of infections. The primary goal in the management of PTDM is to achieve glycemic control to minimize the risk of complications while balancing the need for immunosuppression to maintain the health of the transplanted kidney. This review summarizes the effects of maintenance immunosuppression and therapeutic options among kidney transplant recipients. Patients with PTDM are at increased risk of diabetic kidney disease development; therefore, in this review, we focus on evidence supporting the use of novel antidiabetic agents and discuss their benefits and potential side effects in detail. Full article

(This article belongs to the Special Issue Editorial Board Members’ Collection Series: Chronic Kidney Disease in Diabetes)

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20 pages, 1668 KiB

Open AccessReview

Chronic Kidney Disease in the Older Adult Patient with Diabetes

by Raja Ravender, Maria-Eleni Roumelioti, Darren W. Schmidt, Mark L. Unruh and Christos Argyropoulos

J. Clin. Med. 2024, 13(2), 348; https://doi.org/10.3390/jcm13020348 - 8 Jan 2024

Cited by 3 | Viewed by 7736

Abstract

Diabetes mellitus (DM) and chronic kidney disease (CKD) are common in middle aged and older adult individuals. DM may accelerate the aging process, and the age-related declines in the estimated glomerular filtration rate (eGFR) can pose a challenge to diagnosing diabetic kidney disease (DKD) using standard diagnostic criteria especially with the absence of severe albuminuria among older adults. In the presence of CKD and DM, older adult patients may need multidisciplinary care due to susceptibility to various health issues, e.g., cognitive decline, auditory or visual impairment, various comorbidities, complex medical regimens, and increased sensitivity to medication adverse effects. As a result, it can be challenging to apply recent therapeutic advancements for the general population to older adults. We review the evidence that the benefits from these newer therapies apply equally to older and younger patients with CKD and diabetes type 2 and propose a comprehensive management. This framework will address nonpharmacological measures and pharmacological management with renin angiotensin system inhibitors (RASi), sodium glucose co-transporter 2 inhibitors (SGLT2i), non-steroidal mineralocorticoids receptor antagonists (MRAs), and glucagon like peptide 1 receptor agonists (GLP1-RAs). Full article

(This article belongs to the Special Issue Editorial Board Members’ Collection Series: Chronic Kidney Disease in Diabetes)

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17 pages, 1527 KiB

Open AccessReview

Incretin Therapies for Patients with Type 2 Diabetes and Chronic Kidney Disease

by Radica Z. Alicic and Joshua J. Neumiller

J. Clin. Med. 2024, 13(1), 201; https://doi.org/10.3390/jcm13010201 - 29 Dec 2023

Cited by 5 | Viewed by 2141

Abstract

Since the early 2000s, an influx of novel glucose-lowering agents has changed the therapeutic landscape for treatment of diabetes and diabetes-related complications. Glucagon-like peptide-1 (GLP-1) receptor agonists represent an important therapeutic class for the management of type 2 diabetes (T2D), demonstrating benefits beyond glycemic control, including lowering of blood pressure and body weight, and importantly, decreased risk of development of new or worsening chronic kidney disease (CKD) and reduced rates of atherosclerotic cardiovascular events. Plausible non-glycemic mechanisms that benefit the heart and kidneys with GLP-1 receptor agonists include anti-inflammatory and antioxidant effects. Further supporting their use in CKD, the glycemic benefits of GLP-1 receptor agonists are preserved in moderate-to-severe CKD. Considering current evidence, major guideline-forming organizations recommend the use of GLP-1 receptor agonists in cases of T2D and CKD, especially in those with obesity and/or in those with high cardiovascular risk or established heart disease. Evidence continues to build that supports benefits to the heart and kidneys of the dual GLP-1/glucose-dependent insulinotropic polypeptide (GIP) receptor agonist tirzepatide. Ongoing outcome and mechanistic studies will continue to inform our understanding of the role of GLP-1 and dual GLP-1/GIP receptor agonists in diverse patient populations with kidney disease. Full article

(This article belongs to the Special Issue Editorial Board Members’ Collection Series: Chronic Kidney Disease in Diabetes)

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41 pages, 3897 KiB

Open AccessReview

Pathomechanisms of Diabetic Kidney Disease

by Satyesh K. Sinha and Susanne B. Nicholas

J. Clin. Med. 2023, 12(23), 7349; https://doi.org/10.3390/jcm12237349 - 27 Nov 2023

Cited by 9 | Viewed by 2450

Abstract

The worldwide occurrence of diabetic kidney disease (DKD) is swiftly rising, primarily attributed to the growing population of individuals affected by type 2 diabetes. This surge has been transformed into a substantial global concern, placing additional strain on healthcare systems already grappling with significant demands. The pathogenesis of DKD is intricate, originating with hyperglycemia, which triggers various mechanisms and pathways: metabolic, hemodynamic, inflammatory, and fibrotic which ultimately lead to renal damage. Within each pathway, several mediators contribute to the development of renal structural and functional changes. Some of these mediators, such as inflammatory cytokines, reactive oxygen species, and transforming growth factor β are shared among the different pathways, leading to significant overlap and interaction between them. While current treatment options for DKD have shown advancement over previous strategies, their effectiveness remains somewhat constrained as patients still experience residual risk of disease progression. Therefore, a comprehensive grasp of the molecular mechanisms underlying the onset and progression of DKD is imperative for the continued creation of novel and groundbreaking therapies for this condition. In this review, we discuss the current achievements in fundamental research, with a particular emphasis on individual factors and recent developments in DKD treatment. Full article

(This article belongs to the Special Issue Editorial Board Members’ Collection Series: Chronic Kidney Disease in Diabetes)

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12 pages, 283 KiB

Open AccessReview

Cardiovascular Disease in Diabetes and Chronic Kidney Disease

by Sowmya Swamy, Sahibzadi Mahrukh Noor and Roy O. Mathew

J. Clin. Med. 2023, 12(22), 6984; https://doi.org/10.3390/jcm12226984 - 8 Nov 2023

Cited by 6 | Viewed by 2746

Abstract

Chronic kidney disease (CKD) is a common occurrence in patients with diabetes mellitus (DM), occurring in approximately 40% of cases. DM is also an important risk factor for cardiovascular disease (CVD), but CKD is an important mediator of this risk. Multiple CVD outcomes trials have revealed a greater risk for CVD events in patients with diabetes with CKD versus those without. Thus, reducing the risk of CKD in diabetes should result in improved CVD outcomes. To date, of blood pressure (BP) control, glycemic control, and inhibition of the renin-angiotensin system (RASI), glycemic control appears to have the best evidence for preventing CKD development. In established CKD, especially with albuminuria, RASI slows the progression of CKD. More recently, sodium glucose cotransporter 2 inhibitors (SGLT2i) and glucagon-like peptide receptor agonists (GLP1RA) have revolutionized the care of patients with diabetes with and without CKD. SGLT2i and GLP1RA have proven to reduce mortality, heart failure (HF) hospitalizations, and worsening CKD in patients with diabetes with and without existing CKD. The future of limiting CVD in diabetes and CKD is promising, and more evidence is forthcoming regarding combinations of evidence-based therapies to further minimize CVD events. Full article

(This article belongs to the Special Issue Editorial Board Members’ Collection Series: Chronic Kidney Disease in Diabetes)

12 pages, 581 KiB

Open AccessReview

Management of Hypertension in Diabetic Kidney Disease

by Gates B. Colbert, Mohamed E. Elrggal, Anna Gaddy, Hector M. Madariaga and Edgar V. Lerma

J. Clin. Med. 2023, 12(21), 6868; https://doi.org/10.3390/jcm12216868 - 31 Oct 2023

Viewed by 4952

Abstract

Hypertension is a critical component of cardiovascular disease progression in patients with chronic kidney disease, and specifically diabetic kidney disease (DKD). Causation versus correlation remains up for debate, but what has been confirmed is the delay of DKD progression when hypertension is controlled or moved to guideline drive ranges. Many medications have been studied and used in real world experience for best outcomes, and we discuss below the proven winners thus far making up the renin angiotensin aldosterone system. As well, we discuss guideline changing medications including sodium-glucose cotransporter 2 inhibitors and newer generation mineralocorticoid receptor antagonists. With the growing prevalence of diabetes and DKD in the population, newer agents are emerging in multiple drug class and will be highlighted below. Clinicians continue to search for the optimal care plans for this challenging patient population. Full article

(This article belongs to the Special Issue Editorial Board Members’ Collection Series: Chronic Kidney Disease in Diabetes)

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21 pages, 1264 KiB

Open AccessReview

Pleiotropic Effects of Sodium-Glucose Cotransporter-2 Inhibitors in Cardiovascular Disease and Chronic Kidney Disease

by Anjay Rastogi and James L. Januzzi, Jr.

J. Clin. Med. 2023, 12(8), 2824; https://doi.org/10.3390/jcm12082824 - 12 Apr 2023

Cited by 3 | Viewed by 3866

Abstract

Sodium-glucose cotransporter-2 inhibitors (SGLT2is) have been shown to improve cardiovascular and renal outcomes in patients with established cardiovascular disease, chronic kidney disease (CKD), and heart failure (HF) with reduced or preserved ejection fraction. Clinical benefit has been substantiated in patients with and without type 2 diabetes (T2D). Consequently, SGLT2is have an increasingly important role in HF and CKD management that extends beyond T2D treatment. Their pleiotropic pharmacological effects underlying their cardiovascular and renal benefits are not completely understood but include significant effects beyond blood glucose reduction. SGLT2is inhibit the reabsorption of glucose and sodium in the proximal tubule which, in addition to lowering blood glucose, activates tubuloglomerular feedback, leading to reduced glomerular hydrostatic pressure and the mitigation of glomerular filtration rate loss. SGLT2is have diuretic and natriuretic effects, leading to decreased blood pressure, preload, and left ventricular (LV) filling pressure, and improvements in other surrogates of afterload. In HF, SGLT2is mitigate the risks of hyperkalemia and ventricular arrhythmia and improve LV dysfunction. SGLT2is also reduce sympathetic tone and uric acid levels, increase hemoglobin levels, and are postulated to have anti-inflammatory properties. This narrative review discusses the multifactorial and interrelated pharmacological mechanisms underlying the cardiovascular and renal benefits of SGLT2is. Full article

(This article belongs to the Special Issue Editorial Board Members’ Collection Series: Chronic Kidney Disease in Diabetes)

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