- Review article
- Abstract
- Introduction
- Link between Type 2 Diabetes and Chronic Kidney Disease
- Prevention of Chronic Kidney Disease
- Treatment of Chronic Kidney Disease in Diabetic Patients
- Mineralocorticoid Receptor Antagonists
- Calcium Channel Antagonists
- Glucose Lowering Therapies
- Endothelin Antagonists
- Potential Future Therapeutic Options
- Non-Pharmacological Strategies for Proteinuria Control and Renal Function Preservation
- Evaluation of Clinical Outcomes
- Special Considerations and Challenges
- Conclusion
- References
Management Strategies for the Prevention and Treatment of Chronic Kidney Disease in Patients with Type 2 Diabetes
Rodrigo Antonio Bonilla Figueroa1, Miguel Ángel Gutiérrez Mejía1, Felix Ricardo Bonilla Bonilla1, Marcellina Nwosu2, Dilmareth E. Natera Rodriguez3,4, Bijaya Pariyar5, Peggie C Mendoza Robles6, Isaac Alberto Gomez Hernández1, Prava Basnet7, Kunjan Khanal8, Alejandra José Jaime Sanchez1, Juan Ramón Ventura Cañas1 and Maria Isabel Gomez9*
1Universidad de El Salvador, El Salvador
2American University of Integrative Sciences, Barbados and El Paso Pain Center.
3Universidad De Carabobo, Venezuela
4Department of Neurosurgery, University of Minnesota, USA
5KIST Medical College and Teaching Hospital, Nepal
6Universidad de San Martín de Porres, Perú
7Hebei Medical University, China
8Jalalabad Ragib-Rabeya Medical College, Bangladesh
9Universidad del Valle, México
Submission:September 04, 2023;Published:September 20, 2023
*Corresponding author:Maria Isabel Gomez, Department of Medicine, Universidad del Valle de, Mexico
How to cite this article:Rodrigo A B F, Miguel Ángel G M, Felix Ricardo B B, Marcellina N, Dilmareth E. Natera R, et al. Management Strategies for the Prevention and Treatment of Chronic Kidney Disease in Patients with Type 2 Diabetes. JOJ Urology & Nephrology, 2023; 8(1): 555735. DOI: 10.19080/JOJUN.2023.08.555732
- Review article
- Abstract
- Introduction
- Link between Type 2 Diabetes and Chronic Kidney Disease
- Prevention of Chronic Kidney Disease
- Treatment of Chronic Kidney Disease in Diabetic Patients
- Mineralocorticoid Receptor Antagonists
- Calcium Channel Antagonists
- Glucose Lowering Therapies
- Endothelin Antagonists
- Potential Future Therapeutic Options
- Non-Pharmacological Strategies for Proteinuria Control and Renal Function Preservation
- Evaluation of Clinical Outcomes
- Special Considerations and Challenges
- Conclusion
- References
Abstract
Type 2 diabetes mellitus (DM2) is one of the leading causes of chronic kidney disease (CKD) worldwide. This represents a growing public health problem. It is well known the relationship between chronic kidney disease and type 2 diabetes, and one of the main objectives of the treatment is based on the prevention and education of patients and optimal pharmacological management. The prevention of CKD demands a multifaceted approach that addresses glycemic control, blood pressure management, and lipid control. These preventive measures, combined with dietary modifications, exercise, and patient education, can significantly reduce the risk of CKD development and progression. Accordingly, managing CKD in type 2 diabetes patients demands a comprehensive and individualized approach, considering these conditions’ multifaceted nature. With the right strategies and a patient-centered approach, it is possible to mitigate the impact of CKD, improve patient outcomes, and empower individuals to take control of their health in the face of these complex health challenges. This review article aims to provide a comprehensive overview of pharmacological and non-pharmacological strategies for preventing and treating chronic kidney disease in patients with type 2 diabetes and delay progression to end-stage renal disease (ESRD).
Keywords: Type 2 diabetes mellitus; Chronic kidney disease; End-stage renal disease; Prevention; Education; Pharmacological management; No pharmacological strategies; Exercise, glycemic control; Blood pressure control; lipid control.
Abbreviations: CKD: Chronic Kidney Disease; ESRD: End-Stage Renal Disease; DM2: Type 2 Diabetes Mellitus; RAAS: Renin-Angiotensin-Aldosterone System; ACEIs: Angiotensin-Converting Enzyme Inhibitors; ARBs: Angiotensin Receptor Blockers; MR: Mineralocorticoid Receptor; CCBs: Calcium Channel Blockers; SGLT2: Sodium-Glucose Cotransporter-2 Inhibitors; GLP-1: Glucagon-like Peptide 1; DPP-4: Dipeptidyl Peptidase-4 Inhibitors; GFR: Glomerular Filtration Rate; HbA1c: Hemoglobin A1c; KDIGO: Kidney Disease Improving Global Outcomes
- Review article
- Abstract
- Introduction
- Link between Type 2 Diabetes and Chronic Kidney Disease
- Prevention of Chronic Kidney Disease
- Treatment of Chronic Kidney Disease in Diabetic Patients
- Mineralocorticoid Receptor Antagonists
- Calcium Channel Antagonists
- Glucose Lowering Therapies
- Endothelin Antagonists
- Potential Future Therapeutic Options
- Non-Pharmacological Strategies for Proteinuria Control and Renal Function Preservation
- Evaluation of Clinical Outcomes
- Special Considerations and Challenges
- Conclusion
- References
Introduction
Chronic kidney disease (CKD) represents a significant health concern, particularly in the context of patients with type 2 diabetes. The intertwining of these two conditions poses a complex challenge for healthcare providers and underscores the necessity of effective management strategies [1]. CKD in individuals with type 2 diabetes is characterized by a progressive decline in kidney function over time, which can lead to severe complications, including end-stage renal disease (ESRD) and increased cardiovascular risk. This confluence of diabetes and CKD magnifies the clinical relevance of identifying early signs, implementing appropriate interventions, and advocating for optimal patient outcomes. The clinical relevance of addressing CKD in patients with type 2 diabetes is evident through the alarming prevalence rates of both conditions globally [1,2]. Diabetes, particularly type 2, has reached epidemic proportions, and it is well-established that diabetes is a leading cause of CKD. The bidirectional relationship between diabetes and CKD further necessitates a comprehensive understanding of the underlying mechanisms and effective management strategies [2,3].
The importance of effective management strategies for CKD in patients with type 2 diabetes cannot be overstated. Without intervention, the trajectory of CKD progression can be devastating, leading to substantial morbidity and mortality. Furthermore, CKD amplifies the risk of cardiovascular complications, making it imperative to address kidney health to mitigate overall cardiovascular risk in diabetic individuals. Lifestyle modifications, pharmacological interventions, and close monitoring are integral to managing CKD in patients with type 2 diabetes. Tailoring interventions to individual patient needs and considering the stage of CKD is pivotal in achieving positive outcomes [1,4,5]. This literature review aims to shed light on evaluating management strategies for the prevention and treatment of CKD in patients with type 2 diabetes. By delving into the available research and synthesizing the current body of knowledge, this review aims to provide a comprehensive understanding of the multifaceted approaches to addressing CKD within the context of type 2 diabetes. By exploring the latest evidence-based practices, this review intends to provide the insights necessary for making informed decisions regarding the management of CKD in patients with type 2 diabetes.
- Review article
- Abstract
- Introduction
- Link between Type 2 Diabetes and Chronic Kidney Disease
- Prevention of Chronic Kidney Disease
- Treatment of Chronic Kidney Disease in Diabetic Patients
- Mineralocorticoid Receptor Antagonists
- Calcium Channel Antagonists
- Glucose Lowering Therapies
- Endothelin Antagonists
- Potential Future Therapeutic Options
- Non-Pharmacological Strategies for Proteinuria Control and Renal Function Preservation
- Evaluation of Clinical Outcomes
- Special Considerations and Challenges
- Conclusion
- References
Link between Type 2 Diabetes and Chronic Kidney Disease
Type 2 diabetes and chronic kidney disease (CKD) share a complex and interdependent relationship, with diabetes being one of the leading causes of CKD worldwide [6]. This connection is rooted in the pathogenic mechanisms that underlie both conditions. The relationship between type 2 diabetes and CKD can be explained in several ways. Firstly, hyperglycemia, a hallmark of uncontrolled type 2 diabetes, plays a central role in the development and progression of CKD [6-9]. Elevated blood glucose levels can damage the small blood vessels in the kidneys, impairing their ability to effectively filter waste products from the bloodstream. This process can lead to the accumulation of toxic substances in the body and increased inflammation, ultimately contributing to kidney damage. Secondly, hypertension often coexists with type 2 diabetes. The combination of diabetes and hypertension significantly increases the risk of kidney damage. High blood pressure can cause further injury to the delicate blood vessels within the kidneys, exacerbating kidney function impairment. Moreover, hypertension can also result from kidney dysfunction, creating a vicious cycle that accelerates the progression of CKD [7,8].
Thirdly, the renin-angiotensin-aldosterone system (RAAS) is dysregulated in individuals with type 2 diabetes. This hormonal system is crucial in regulating blood pressure and fluid balance. In diabetes, the RAAS can become overactive, leading to increased blood pressure and the promotion of kidney inflammation and fibrosis, which are hallmarks of CKD. Fourthly, diabetesrelated metabolic abnormalities, such as dyslipidemia and oxidative stress, can further contribute to kidney damage [8,9]. Dyslipidemia involves abnormal lipid profiles, including high levels of triglycerides and low-density lipoprotein cholesterol, which can impair kidney function and promote inflammation. Oxidative stress, resulting from producing harmful free radicals, can also cause cellular damage within the kidneys [6,10].
Additionally, obesity, a common comorbidity of type 2 diabetes, can exacerbate kidney strain. Excess body fat can lead to inflammation and insulin resistance, worsening kidney function and promoting CKD development. Genetics may also affect the relationship between type 2 diabetes and CKD, as certain genetic factors can predispose individuals to both conditions [7,11].
Accordingly, the relationship between type 2 diabetes and chronic kidney disease is multifaceted and characterized by a web of pathogenic mechanisms. Hyperglycemia, hypertension, dysregulation of the RAAS system, metabolic abnormalities, obesity, and genetic factors all contribute to the increased risk of CKD in individuals with type 2 diabetes. Managing diabetes through lifestyle changes, medication, and blood pressure control is crucial in preventing and slowing the progression of CKD in these patients [11]. Moreover, regular monitoring and early intervention are essential in identifying and managing kidney disease in individuals with diabetes to mitigate the potentially severe consequences of this dual burden of chronic conditions.
- Review article
- Abstract
- Introduction
- Link between Type 2 Diabetes and Chronic Kidney Disease
- Prevention of Chronic Kidney Disease
- Treatment of Chronic Kidney Disease in Diabetic Patients
- Mineralocorticoid Receptor Antagonists
- Calcium Channel Antagonists
- Glucose Lowering Therapies
- Endothelin Antagonists
- Potential Future Therapeutic Options
- Non-Pharmacological Strategies for Proteinuria Control and Renal Function Preservation
- Evaluation of Clinical Outcomes
- Special Considerations and Challenges
- Conclusion
- References
Prevention of Chronic Kidney Disease
Chronic Kidney Disease (CKD) is a severe and widespread health concern characterized by the gradual loss of kidney function over time. Its impact on global public health cannot be understated, as CKD is associated with an increased risk of cardiovascular disease, kidney failure, and mortality. Given the significant burden of CKD, prevention strategies have gained paramount importance [12-14]. The prevention of CKD demands a multifaceted approach that addresses glycemic control, blood pressure management, and lipid control. These preventive measures, combined with dietary modifications, exercise, and patient education, can significantly reduce the risk of CKD development and progression. A comprehensive strategy that targets modifiable risk factors and empowers individuals to take charge of their health is pivotal in mitigating the global burden of CKD [13].
Glycemic Control
Glycemic control plays a pivotal role in preventing the onset and progression of CKD, particularly in individuals with diabetes mellitus. Hyperglycemia contributes to the pathogenesis of CKD by promoting inflammation, oxidative stress, and endothelial dysfunction. Thus, maintaining optimal glycemic levels through lifestyle modifications and pharmacological interventions is essential. Diabetes-specific education on self-monitoring blood glucose levels, adherence to prescribed medications, and adopting a balanced diet with controlled carbohydrate intake can significantly reduce the risk of CKD development [12,14].
Blood Pressure Management
Hypertension is a significant risk factor for CKD, as sustained elevated blood pressure exerts undue stress on the renal vasculature and filtration apparatus. Aggressive blood pressure control, particularly in individuals with diabetes or proteinuria, has been proven effective in retarding the progression of CKD [13]. Lifestyle modifications, including sodium restriction, increased physical activity, and weight management, are the cornerstone of blood pressure management. Pharmacological interventions targeting the renin-angiotensin-aldosterone system, such as angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin II receptor blockers (ARBs), have demonstrated renoprotective effects by reducing intraglomerular pressure and proteinuria [16,17].
Lipid Control
Dyslipidemia is implicated in CKD progression due to its role in endothelial dysfunction, atherosclerosis, and inflammation. Lipid-lowering therapies, primarily with statins, have shown promise in preventing CKD progression by modulating lipid profiles and attenuating oxidative stress. However, the impact of lipid control on CKD prevention is more pronounced in individuals with concomitant cardiovascular disease risk factors [14,16]. Lifestyle modifications, including adopting a hearthealthy diet and engaging in regular physical activity, complement pharmacological interventions to achieve optimal lipid control. Moreover, dietary interventions are critical for CKD prevention. A well-balanced diet rich in vegetables, fruits, whole grains, lean proteins, and healthy fats can aid in weight management, blood pressure control, and glycemic regulation. Specifically, the Dietary Approaches to Stop Hypertension (DASH) diet, characterized by its emphasis on sodium restriction and high potassium intake, has demonstrated effectiveness in reducing blood pressure and proteinuria, both crucial factors in CKD prevention. Additionally, protein intake should be carefully managed, as excessive protein consumption can exacerbate renal damage in individuals with compromised kidney function [18].
Lifestyle Modification
Lifestyle modification such as weight loss, exercise, and diet modification are nephroprotective. It has been shown to reduce the incidence of hypertension and diabetes and in turn CKD in these patients [45]. The use of dietary interventions, such as reducing salt intake and adopting meals abundant in fruits and vegetables while minimizing saturated fat consumption, have demonstrated efficacy in lowering blood pressure levels [45]. Regular physical activity contributes significantly to CKD prevention. Exercise helps maintain a healthy weight, improve insulin sensitivity, and enhance cardiovascular fitness. Aerobic exercises, such as brisk walking, cycling, and swimming, are recommended for at least 150 minutes weekly. Resistance training can also play a role in preserving muscle mass and overall functional capacity. However, exercise intensity and duration should be tailored to individual capabilities, considering the potential risk of overexertion in individuals with advanced CKD [12,15].
Patient Education
Patient education serves as a cornerstone for CKD prevention by empowering individuals to make informed decisions about their health. Diabetes education, encompassing self-care practices, medication adherence, and regular monitoring, is crucial for at-risk people. Education regarding the importance of medication adherence, lifestyle modifications, and regular follow-up appointments aids in optimizing blood pressure and lipid control. Patients should be educated about the signs and symptoms of CKD progression, emphasizing the need for early medical intervention [14,17].
- Review article
- Abstract
- Introduction
- Link between Type 2 Diabetes and Chronic Kidney Disease
- Prevention of Chronic Kidney Disease
- Treatment of Chronic Kidney Disease in Diabetic Patients
- Mineralocorticoid Receptor Antagonists
- Calcium Channel Antagonists
- Glucose Lowering Therapies
- Endothelin Antagonists
- Potential Future Therapeutic Options
- Non-Pharmacological Strategies for Proteinuria Control and Renal Function Preservation
- Evaluation of Clinical Outcomes
- Special Considerations and Challenges
- Conclusion
- References
Treatment of Chronic Kidney Disease in Diabetic Patients
Inhibition of the Renin-Angiotensin-Aldosterone System
Pharmacological therapy with modulators of the reninangiotensin- aldosterone system (RAAS), such as angiotensinconverting enzyme inhibitors (ACEIs) and angiotensin receptor blockers (ARBs), has been pivotal for kidney protection in diabetic patients for decades. Hypertension is a crucial step in the progression of kidney disease. Antihypertensive therapy, mainly through ACEIs or ARBs, reduces the risk of albuminuria and prevents progression to end-stage renal disease in type 1 or 2 diabetics with established CKD (eGFR <60 ml/min/1.73m² and albumin-to-creatinine ratio (UACR) of 300 mg/g creatinine) [19]. It’s suggested to maintain a blood pressure of <130/80 mmHg in diabetics to reduce mortality from cardiovascular disease and progression of kidney disease, tailoring this recommendation based on individual risks and benefits [19]. The relevance of inhibiting the RAAS for renal protection has been recognized since the 1980s, with numerous studies showing reduced albuminuria and renoprotective benefits. The results from landmark trials like RENAAL and IDNT, where the efficacy of losartan and irbesartan was assessed, respectively, underscore the significance of these drugs in renal protection in the context of diabetes [20]. However, it’s important to note that combining multiple agents targeting the RAAS might increase adverse risks without clear additional benefits [21]; these findings, emerging from studies like the ONTARGET trial, advise against the combined therapy of ACEIs and ARBs [21]. In diabetic patients without hypertension and without albuminuria, ACE inhibitors have shown a potential to delay the onset of microalbuminuria and protect renal function. However, due to a lack of robust evidence, current clinical guidelines do not recommend their preventive use [22].
- Review article
- Abstract
- Introduction
- Link between Type 2 Diabetes and Chronic Kidney Disease
- Prevention of Chronic Kidney Disease
- Treatment of Chronic Kidney Disease in Diabetic Patients
- Mineralocorticoid Receptor Antagonists
- Calcium Channel Antagonists
- Glucose Lowering Therapies
- Endothelin Antagonists
- Potential Future Therapeutic Options
- Non-Pharmacological Strategies for Proteinuria Control and Renal Function Preservation
- Evaluation of Clinical Outcomes
- Special Considerations and Challenges
- Conclusion
- References
Mineralocorticoid Receptor Antagonists
The mineralocorticoid receptor (MR) has diverse roles, extending beyond its action on the collecting tubules’ epithelial sodium channels (ENaC). It is found in various tissues, such as the heart and blood vessels, and regulates the transport of fluids and ions. Excessive activation of MR can increase reactive oxygen species and inflammation and cause renal hypertrophy [20]. The first MR antagonists, spironolactone and eplerenone, were shown to reduce proteinuria in patients already treated with RAAS blockers. Despite these benefits, their use is cautiously approached due to the risks of hyperkalemia, and more research is needed regarding their impact on renal progression [20]. Finerenone, a non-steroidal MRA, has shown potential, especially with lower risks of hyperkalemia. The FIDELIO-DKD trial validated its efficacy in diabetic kidney disease, reducing the risk of adverse renal outcomes [21].
- Review article
- Abstract
- Introduction
- Link between Type 2 Diabetes and Chronic Kidney Disease
- Prevention of Chronic Kidney Disease
- Treatment of Chronic Kidney Disease in Diabetic Patients
- Mineralocorticoid Receptor Antagonists
- Calcium Channel Antagonists
- Glucose Lowering Therapies
- Endothelin Antagonists
- Potential Future Therapeutic Options
- Non-Pharmacological Strategies for Proteinuria Control and Renal Function Preservation
- Evaluation of Clinical Outcomes
- Special Considerations and Challenges
- Conclusion
- References
Calcium Channel Antagonists
Treatment with angiotensin receptor blockers improves renal function. However, it often fails to control blood pressure on its own, necessitating the addition of other drugs, such as calcium channel blockers (CCBs), for optimal renal benefit [23]. While some studies show advantages in the antiproteinuric efficacy of ACE inhibitors over CCBs in the short term, in the long run, both drugs provide similar benefits in preventing the progression of nephropathy in diabetics. Combining both can maximize the reduction of albuminuria, and CCBs are a valuable option when seeking alternatives to RAAS blockers or reducing side effects. More studies are needed to provide solid evidence [23].
- Review article
- Abstract
- Introduction
- Link between Type 2 Diabetes and Chronic Kidney Disease
- Prevention of Chronic Kidney Disease
- Treatment of Chronic Kidney Disease in Diabetic Patients
- Mineralocorticoid Receptor Antagonists
- Calcium Channel Antagonists
- Glucose Lowering Therapies
- Endothelin Antagonists
- Potential Future Therapeutic Options
- Non-Pharmacological Strategies for Proteinuria Control and Renal Function Preservation
- Evaluation of Clinical Outcomes
- Special Considerations and Challenges
- Conclusion
- References
Glucose Lowering Therapies
SGLT2: Sodium-glucose Cotransporter-2 Inhibitors (SGLT2) are the primary transporter in the proximal tubules responsible for glucose reabsorption from the glomerular filtrate [24]. SGLT2 inhibitors block this reabsorption, leading to hemodynamic effects, including tubuloglomerular feedback that reduces intraglomerular pressure. The improvement in albuminuria is multifactorial, not only associated with vasoconstriction of the afferent arteriole and the reduction of hyperfiltration but also with the improvement of systemic blood pressure [25]. In addition, these inhibitors redirect metabolism towards gluconeogenesis and ketogenesis, providing additional protection to the heart and kidneys and reducing glucotoxicity and mitochondrial inflammation in tubular cells [25]. Studies such as DECLARE-TIMI 58 and the CANVAS program have significantly improved renal outcomes in patients taking SGLT2 inhibitors, including dapagliflozin and canagliflozin [24,26]. For these reasons, SGLT2 is recommended in patients with stage 3 CKD or higher and type 2 diabetes, as they beneficially affect the progression of CKD, regardless of glycemic control [19].
GLP1: Glucagon-like peptide 1 (GLP-1) is an incretin hormone secreted by intestinal L cells in response to food intake and elevations in plasma glucose, facilitating insulin secretion and suppressing that of glucagon. Beyond these effects, GLP-1 has demonstrated renal protective benefits, such as inhibiting angiotensin II-induced inflammation, oxidative stress and reducing albuminuria [20]. In clinical trials like AWARD-7 and REWIND, it was observed that GLP-1 agonists, particularly dulaglutide, exhibit positive renal effects, maintaining or improving markers such as UACR and marginally eGFR [20]. However, whether albuminuria is a clinically relevant renal outcome is still unclear. Despite the promising evidence of GLP-1RAs in diabetic kidney disease (DKD), more research is still needed to fully understand their roles and how they should be used in clinical practice [27].
DPP4: Dipeptidyl Peptidase-4 Inhibitors (DPP-4) have emerged as a potentially beneficial option for patients with CKD. Trials such as SAVOR-TIMI 53 and CARMELINA have highlighted an apparent reduction in albuminuria in those treated with these inhibitors. However, it’s essential to note that no significant reduction in the risk of disease progression was evidenced. Despite these preliminary findings, additional studies are required to determine the efficacy and the full scope of the benefits of DPP-4 inhibitors in the context of diabetic nephropathy [20,21,28].
- Review article
- Abstract
- Introduction
- Link between Type 2 Diabetes and Chronic Kidney Disease
- Prevention of Chronic Kidney Disease
- Treatment of Chronic Kidney Disease in Diabetic Patients
- Mineralocorticoid Receptor Antagonists
- Calcium Channel Antagonists
- Glucose Lowering Therapies
- Endothelin Antagonists
- Potential Future Therapeutic Options
- Non-Pharmacological Strategies for Proteinuria Control and Renal Function Preservation
- Evaluation of Clinical Outcomes
- Special Considerations and Challenges
- Conclusion
- References
Endothelin Antagonists
While it has been shown that endothelin receptor antagonism enhances renal microcirculation and may decrease urinary protein excretion, the most representative trials yielded unfavorable results. These studies revealed safety concerns linked to volume overload and congestive heart failure [20].
- Review article
- Abstract
- Introduction
- Link between Type 2 Diabetes and Chronic Kidney Disease
- Prevention of Chronic Kidney Disease
- Treatment of Chronic Kidney Disease in Diabetic Patients
- Mineralocorticoid Receptor Antagonists
- Calcium Channel Antagonists
- Glucose Lowering Therapies
- Endothelin Antagonists
- Potential Future Therapeutic Options
- Non-Pharmacological Strategies for Proteinuria Control and Renal Function Preservation
- Evaluation of Clinical Outcomes
- Special Considerations and Challenges
- Conclusion
- References
Potential Future Therapeutic Options
Inflammatory pathways play a crucial role in the progression of CKD, sparking interest in pharmacological approaches centered on these. Baricitinib, by inhibiting JAK1/JAK2, has shown potential in reducing albuminuria, but its impact on the progression of DKD remains uncertain. Other therapies under study include antifibrotic treatments such as pirfenidone or pentoxifylline Nox1/4 inhibition, and cytokine chemokine inhibition. Future research is anticipated to determine the effectiveness and integration of these treatments in managing CKD [20].
- Review article
- Abstract
- Introduction
- Link between Type 2 Diabetes and Chronic Kidney Disease
- Prevention of Chronic Kidney Disease
- Treatment of Chronic Kidney Disease in Diabetic Patients
- Mineralocorticoid Receptor Antagonists
- Calcium Channel Antagonists
- Glucose Lowering Therapies
- Endothelin Antagonists
- Potential Future Therapeutic Options
- Non-Pharmacological Strategies for Proteinuria Control and Renal Function Preservation
- Evaluation of Clinical Outcomes
- Special Considerations and Challenges
- Conclusion
- References
Non-Pharmacological Strategies for Proteinuria Control and Renal Function Preservation
Weight Loss: Maintaining an active lifestyle and managing weight becomes a cornerstone strategy for delaying the progression of chronic kidney disease. In the Look Ahead trial, which included 5,145 individuals with type 2 diabetes and obesity, it was demonstrated that an intensive lifestyle intervention led to an average weight reduction of 4 kg. More notably, this intervention decreased the relative risk of onset of very high-risk chronic kidney disease (as per the KDIGO classification system) by approximately 30% [21]. Additionally, it’s essential to highlight gastric bypass surgery as an emerging strategy. This procedure has proven effective in remitting albuminuria in individuals with type 2 diabetes, obesity, and microalbuminuria. Therefore, it might be considered a viable therapeutic option for selected individuals [21].
Protein Restriction: Dietary protein restriction has been a focus of research for the management of patients with CKD. Data from the “Modification of Diet in Renal Disease” study, conducted in non-diabetic patients, revealed that while the immediate effects of protein restriction were inconclusive, subsequent analyses suggested benefits from this intervention, including reductions in blood pressure and proteinuria. However, it is essential to consider the potential for loss of muscle mass and strength, especially in more fragile patients or those over 80. Current guidelines suggest protein intake between 0.6 and 0.8 g/kg per day for those with significant albuminuria [21]. On the other hand, a review encompassing eight randomized controlled trials (RCT) on the subject evaluated the difference between lowprotein diets (LPD) and usual-protein diets (UPD) in people with diabetic nephropathy. This review concluded that, despite current recommendations, the certainty of evidence regarding protein restriction is low or very low. Even though clinical guidelines, such as those from KDOQI 2020, suggest an intake of 0.6 to 0.8 g/kg/ day, it is essential to inform patients about the paucity of highquality evidence supporting these benefits [29].
- Review article
- Abstract
- Introduction
- Link between Type 2 Diabetes and Chronic Kidney Disease
- Prevention of Chronic Kidney Disease
- Treatment of Chronic Kidney Disease in Diabetic Patients
- Mineralocorticoid Receptor Antagonists
- Calcium Channel Antagonists
- Glucose Lowering Therapies
- Endothelin Antagonists
- Potential Future Therapeutic Options
- Non-Pharmacological Strategies for Proteinuria Control and Renal Function Preservation
- Evaluation of Clinical Outcomes
- Special Considerations and Challenges
- Conclusion
- References
Evaluation of Clinical Outcomes
The prevention and treatment of CKD in DM2 requires a comprehensive approach considering clinical indicators such as GFR, proteinuria, and blood pressure. Glycemic control, blood pressure management, and renin-angiotensin system inhibition have demonstrated efficacy in improving clinical outcomes in DM2- related CKD. However, the optimal balance between aggressive intervention and potential risks necessitates individualized treatment approaches. A thorough understanding of the available evidence is crucial for healthcare providers to make informed decisions in managing CKD in individuals with DM2. First, the glomerular filtration rate is a vital indicator of kidney function, reflecting the rate at which the kidneys filter waste and excess fluids from the bloodstream. In individuals with DM2, declining GFR is a hallmark of CKD progression. Monitoring GFR provides insights into the severity of renal impairment and aids in disease staging [30-33]. Slowed GFR decline signifies successful management and may result from interventions that target glycemic control, blood pressure regulation, and lipid management [34,35]. Secondly, proteinuria, particularly albuminuria, signifies renal damage and is predictive of adverse outcomes in DM2-related CKD. Increased urinary protein excretion is indicative of glomerular dysfunction and renal inflammation. Effective management strategies aim to reduce or prevent proteinuria, as its persistence is linked to heightened cardiovascular risk and CKD progression. Strategies combining blood pressure control and renin-angiotensin system inhibition have effectively reduced proteinuria and slowed CKD progression [32,33].
Hypertension is both a cause and consequence of CKD in DM2. Elevated blood pressure contributes to kidney damage by increasing intraglomerular pressure and promoting vascular dysfunction. Controlling blood pressure is pivotal in CKD management, as it can significantly impact disease progression. Studies have shown that tighter blood pressure control, aiming for lower targets, is associated with reduced rates of GFR decline and cardiovascular events in DM2 patients with CKD. The landmark SPRINT trial investigated intensive blood pressure control in individuals with Hypertension, including those with DM2. This study highlighted that targeting a systolic blood pressure of <120 mm Hg, compared to the standard target of <140 mm Hg, resulted in lower rates of cardiovascular events and progression of CKD. Such aggressive blood pressure control is particularly beneficial for individuals with DM2 and CKD, as it mitigates renal damage [33-36].
Several clinical trials have explored the impact of glycemic control on CKD outcomes in DM2. The ADVANCE study demonstrated that intensive glycemic control, achieved through antidiabetic medications, reduced the risk of microalbuminuria and nephropathy progression. Similarly, the ACCORD trial suggested a trend toward reduced risk of microalbuminuria with intensive glucose-lowering therapy [34,36,37]. However, the benefit of tight glycemic control in advanced CKD remains uncertain and requires careful consideration of potential hypoglycemia risks. Finally, numerous studies have emphasized the importance of renin-angiotensin system inhibition in CKD management. The RENAAL trial established that the angiotensin receptor blocker losartan reduced the risk of end-stage renal disease and mortality in individuals with DM2-related nephropathy. Similarly, the IDNT study demonstrated that the angiotensin-converting enzyme inhibitor irbesartan reduced the risk of CKD progression and adverse cardiovascular events [8]. These findings underline the central role of renin-angiotensin system inhibition in CKD management.
- Review article
- Abstract
- Introduction
- Link between Type 2 Diabetes and Chronic Kidney Disease
- Prevention of Chronic Kidney Disease
- Treatment of Chronic Kidney Disease in Diabetic Patients
- Mineralocorticoid Receptor Antagonists
- Calcium Channel Antagonists
- Glucose Lowering Therapies
- Endothelin Antagonists
- Potential Future Therapeutic Options
- Non-Pharmacological Strategies for Proteinuria Control and Renal Function Preservation
- Evaluation of Clinical Outcomes
- Special Considerations and Challenges
- Conclusion
- References
Special Considerations and Challenges
Managing chronic kidney disease (CKD) in patients with type 2 diabetes presents unique challenges that require careful consideration. This article discusses these challenges and outlines evidence-based strategies supported by literature. Among them are:
Polypharmacy Management
CKD and diabetes patients often require multiple medications to manage their conditions, including glucoselowering drugs, blood pressure medications, and medications to address complications. These patients frequently experience polypharmacy, which is one patient’s use of many drugs. Polypharmacy is allegedly becoming more common in therapy, especially among older patients. This can lead to medication non-adherence and an increased risk of medication-related issues [38-41]. A study on diabetes management in older adults with CKD recommends personalized treatment plans that target glycemic control, weight management, and reducing the risk of polypharmacy. Clinicians should collaborate with patients to develop individualized goals [39,42].
Individualized Treatment
Treatment plans should be tailored to each patient’s specific needs, taking into account their stage of CKD, comorbidities, and medication tolerance. Monitoring kidney function and glucose control regularly is essential to make any necessary adjustments [43]. Consider deprescribing medications that may no longer provide significant benefits. Whenever possible, healthcare providers should simplify medication regimens. Once-daily medications and combination therapies can reduce the pill burden and improve adherence [42].
Comorbidities and CKD Progression
Patients with type 2 diabetes and CKD often have comorbid conditions like hypertension, cardiovascular disease, and dyslipidemia. Managing these alongside diabetes and CKD can be complex. Additionally, CKD’s progressive and unpredictable nature adds complexity to treatment planning. Regular monitoring of kidney function (e.g., eGFR and albuminuria) and glucose control (e.g., HbA1c) is essential, with adjustments based on these results. Accompanied by strict blood pressure control, the recommendation is to prescribe medications like ACE inhibitors or ARBs, which are crucial in decreasing CKD progression due to their renoprotective effects [39,43].
Nutritional Challenges
CKD often requires dietary restrictions to maintain electrolyte and fluid balance. Balancing these restrictions with diabetes dietary requirements can be challenging. Furthermore, monitoring the risk of hypoglycemia is essential, as some glucose-lowering medications may increase the risk, which can be particularly dangerous for CKD patients as it may exacerbate kidney function [43,44].
Collaborative Care and Patient Education
Engage a multidisciplinary team, including nephrologists, endocrinologists, dietitians, and pharmacists, to provide comprehensive care. Empower patients with knowledge about their conditions, including dietary guidelines and medications. Collaborate with patients to establish individualized treatment goals and involve them in care decisions. Encourage a healthy lifestyle, encompassing dietary modifications, regular physical activity, and smoking cessation, to improve overall health and effectively manage both conditions. Additionally, addressing mental health issues, such as depression and anxiety, as these conditions can impact self-management and adherence [39,43,44]. This comprehensive approach improves patient outcomes and empowers individuals to actively participate in their healthcare journey. In CKD management, customization and vigilance are the keys to success, guaranteeing that every patient receives the personalized care they need to attain the highest attainable quality of life.
- Review article
- Abstract
- Introduction
- Link between Type 2 Diabetes and Chronic Kidney Disease
- Prevention of Chronic Kidney Disease
- Treatment of Chronic Kidney Disease in Diabetic Patients
- Mineralocorticoid Receptor Antagonists
- Calcium Channel Antagonists
- Glucose Lowering Therapies
- Endothelin Antagonists
- Potential Future Therapeutic Options
- Non-Pharmacological Strategies for Proteinuria Control and Renal Function Preservation
- Evaluation of Clinical Outcomes
- Special Considerations and Challenges
- Conclusion
- References
Conclusion
The coexistence of type 2 diabetes and chronic kidney disease (CKD) represents a significant and intricate healthcare challenge. This review has highlighted the intertwined nature of these two conditions, emphasizing the urgency of effective management strategies. The clinical relevance of addressing CKD in type 2 diabetes patients is indisputable, given the alarming global prevalence rates of both diseases. As diabetes reaches epidemic proportions, its status as a leading cause of CKD is a critical concern. The bidirectional relationship between diabetes and CKD underscores the need to understand underlying mechanisms and implement practical management approaches thoroughly. Effective management is paramount because CKD’s trajectory can be devastating without intervention, leading to substantial morbidity and mortality. Moreover, CKD magnifies the risk of cardiovascular complications, making it imperative to address kidney health to mitigate overall cardiovascular risk in diabetic individuals. Lifestyle modifications, pharmacological interventions, and close monitoring are integral to managing CKD in type 2 diabetes patients. Individualized interventions tailored to each patient’s needs and CKD stage are pivotal in achieving positive outcomes. A multifaceted approach targeting glycemic control, blood pressure management, lipid control, lifestyle modifications, and patient education has been discussed in the prevention of CKD. These measures, when combined, significantly reduce the risk of CKD development and progression, highlighting the importance of addressing modifiable risk factors and empowering individuals to take control of their health. In the treatment of CKD in diabetic patients, various pharmacological therapies have been explored, including the inhibition of the renin-angiotensin-aldosterone system, mineralocorticoid receptor antagonists, calcium channel antagonists, and glucose-lowering therapies such as SGLT2 inhibitors, GLP1 agonists, and DPP4 inhibitors. Each of these therapies has shown potential in managing CKD and preventing its progression. Evaluating clinical outcomes emphasizes the significance of monitoring GFR and proteinuria, vital indicators of kidney function and damage in type 2 diabetes-related CKD. Effective management strategies have demonstrated efficacy in improving these clinical outcomes. Finally, the review addresses the special considerations and challenges in managing CKD in type 2 diabetes patients, such as polypharmacy management, individualized treatment, comorbidities, nutritional challenges, and the importance of collaborative care and patient education. Accordingly, managing CKD in type 2 diabetes patients demands a comprehensive and individualized approach, considering these conditions’ multifaceted nature. With the right strategies and a patient-centered approach, it is possible to mitigate the impact of CKD, improve patient outcomes, and empower individuals to take control of their health in the face of these complex health challenges.
- Review article
- Abstract
- Introduction
- Link between Type 2 Diabetes and Chronic Kidney Disease
- Prevention of Chronic Kidney Disease
- Treatment of Chronic Kidney Disease in Diabetic Patients
- Mineralocorticoid Receptor Antagonists
- Calcium Channel Antagonists
- Glucose Lowering Therapies
- Endothelin Antagonists
- Potential Future Therapeutic Options
- Non-Pharmacological Strategies for Proteinuria Control and Renal Function Preservation
- Evaluation of Clinical Outcomes
- Special Considerations and Challenges
- Conclusion
- References
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