Diagnosis Diabetic Nephropathy: An Updated Guide for Healthcare Professionals

Introduction

Diabetic nephropathy, now frequently referred to as diabetic kidney disease (DKD), remains the primary cause of end-stage renal disease (ESRD) across developed nations, including the United States. This microvascular complication is a significant concern for individuals with both type 1 diabetes (T1D) and type 2 diabetes (T2D). Early and accurate diagnosis of diabetic nephropathy is paramount as timely, aggressive intervention can substantially slow or even halt disease progression. While DKD can manifest in both T1D and T2D, the majority of cases are associated with T2D, which is characterized by insulin resistance.

Recent advancements in understanding diabetes mellitus and its complications have led to crucial updates in diagnostic and treatment guidelines. Keeping abreast of these developments is essential for healthcare providers aiming to deliver optimal care to patients facing the dual challenge of diabetes and kidney disease. It’s important to note the evolving terminology; while “diabetic nephropathy” is historically used, leading organizations like Kidney Disease: Improving Global Outcomes (KDIGO) now recommend “diabetes and chronic kidney disease (CKD)” or “diabetic kidney disease (DKD)”. Regardless of terminology, a multidisciplinary approach, emphasizing holistic care and lifestyle adjustments, remains fundamental to effective management.

Etiology and Pathophysiology

Hyperglycemia, the hallmark of diabetes, sets in motion a cascade of events leading to diabetic nephropathy. This begins with the overproduction of reactive oxygen species and the activation of several key molecular pathways. These include:

• Advanced Glycemic End Products (AGEs) Formation: The non-enzymatic glycation of proteins and lipids, leading to tissue damage and inflammation.
• Increased Oxidative Stress: An imbalance between the production of reactive oxygen species and antioxidant defenses, causing cellular damage.
• Activation of Nuclear Factor Kappa B (NF-κB) and Protein Kinase C (PKC): Signaling pathways that promote inflammation and fibrosis.
• Upregulation of Transforming Growth Factor-beta (TGF-β)/SMAD: A key pathway driving fibrosis and extracellular matrix deposition.
• Heightened Lipotoxicity: Accumulation of toxic lipid intermediates in kidney cells, contributing to dysfunction.

At the cellular level, these pathways manifest as abnormal cell signaling, increased extracellular matrix formation, and thickening of the glomerular basement membrane (GBM). A critical element is marked inflammation, fueled by elevated cytokines and chemokines, which leads to fibrosis and increased vascular permeability. These interconnected mechanisms drive the development and progression of diabetic nephropathy through inflammation, fibrosis, endothelial dysfunction, and podocyte damage. Understanding these mechanisms is crucial for refining Diagnosis Diabetic Nephropathy and developing targeted therapies.

Macrophage Activation in DKD

Hyperglycemia promotes the formation of glucose degradation products and AGEs, intensifying inflammation and driving macrophage infiltration into the kidneys. This macrophage infiltration is a central feature in the pathogenesis of diabetic nephropathy. Immune complexes and cytokines, notably TGF-β1 (secreted by macrophages) and intracellular cell adhesion molecule-1 (ICAM-1, produced by renal tubular cells), play vital roles in this inflammatory process. Studies have correlated the presence of CD163+ macrophages in renal tissue with the severity of diabetic nephropathy, interstitial fibrosis, tubular atrophy, and glomerulosclerosis. Macrophages contribute to renal fibrosis by attracting fibroblasts and can even transform into myofibroblasts, further accelerating fibrotic progression.

Macrophages also activate the renin-angiotensin-aldosterone system (RAAS), leading to alterations in renal hemodynamics and further macrophage recruitment through factors like monocyte chemoattractant protein-1 (MCP-1), osteopontin, and adhesion molecules. Research is increasingly focusing on the tubulointerstitial aspects of DKD, with studies suggesting that macrophage infiltration in the tubulointerstitium correlates more strongly with declining GFR and renal fibrosis than glomerular macrophage infiltration. Tubular epithelial cells can also transform into mesenchymal cells, contributing to extracellular matrix secretion and fibroblast proliferation.

Several medications are known to reduce macrophage activity in DKD, including:

• RAAS inhibitors: Reduce MCP-1 expression.
• Pioglitazone: Reduces NF-κB expression.
• Vitamin D-25(OH): Decreases macrophage adhesion.

Endothelial Cell Damage in Diabetic Nephropathy

Endothelial cell damage is an early pathological change in diabetic nephropathy. This damage generates reactive oxygen species, critical in the progression of DKD. Hyperglycemia and hemodynamic changes trigger the release of cell adhesion molecules, glycosaminoglycans, and chemokines, amplifying the immune response and causing direct endothelial damage, further exacerbated by endothelial-to-mesenchymal transition.

Podocyte Damage and Proteinuria

Podocytes, essential for the glomerular filtration barrier, are vulnerable to injury in diabetic nephropathy, leading to proteinuria. Podocyte injury can involve hypertrophy, reduced density, and apoptosis, driven by factors like lipotoxicity, oxidative stress, mitochondrial dysfunction, vascular dysfunction, and impaired autophagy. Podocyte damage is also linked to reduced nephrin expression and impaired insulin-like growth factor-1 (IGF-1)/insulin receptor signaling pathways.

Therapeutic strategies targeting podocyte damage, explored in clinical and preclinical trials, include:

• Lipid-lowering agents (Statins, Resveratrol): Reduce lipid accumulation.
• Atrasentan (with losartan): May increase podocyte number.
• Spironolactone: Decreases RAAS activation and may reduce autophagy.
• Sacubitril/valsartan: May decrease inflammation, oxidative stress, and blood sugar levels.
• Glucagon-like peptide-1 (GLP-1) inhibitors: Reduce oxidative stress and apoptosis.
• Sodium-glucose cotransporter-2 (SGLT2) inhibitors: May reduce oxidative stress and apoptosis.

Polyol Pathway and Uric Acid in DKD

The polyol pathway contributes to diabetic nephropathy through fructose and sorbitol accumulation, glucose byproducts that increase osmotic pressure, leading to edema and cell membrane rupture. Fructose metabolism produces urate, contributing to insulin resistance, endothelial dysfunction, and renal tubular injury. Hyperuricemia also activates RAAS and may be a cardiovascular risk factor. Fructose also contributes to oxidative stress. Aldose reductase inhibitors, targeting the rate-limiting step of the polyol pathway, have shown promise in reversing diabetic nephropathy lesions in animal models.

Genetic Predisposition to Diabetic Nephropathy

Genetics plays a significant role in diabetic nephropathy development, with both genetic and environmental factors contributing. A family history of diabetes or kidney disease increases risk. Specific gene variations have been associated with DKD, including polymorphisms in the ACE gene, potentially influencing ACE inhibitor (ACEI) and angiotensin receptor blocker (ARB) therapy responses. Epigenetic mechanisms, influenced by prolonged hyperglycemia, including DNA methylation, histone modifications, and noncoding RNA regulation, also play a role in gene-environment interactions in DKD.

Epidemiology of Diabetic Nephropathy

Data from the Centers for Disease Control and Prevention (CDC) in the United States indicates that 14% of adults aged 20 or older have CKD, with 30% of these cases linked to diabetes. Approximately 30% to 40% of individuals with diabetes mellitus will develop diabetic nephropathy. Global projections are alarming, with diabetes incidence expected to exceed 783 million by 2045, and diabetic complications predicted to be the seventh leading cause of mortality by 2030. These figures underscore the growing public health challenge posed by diabetic nephropathy and the critical need for effective diagnosis diabetic nephropathy strategies.

Pathophysiology and Stages of Diabetic Nephropathy

In T2D, albuminuria may be present at the time of diabetes diagnosis, whereas diabetic nephropathy in T1D typically develops 15 to 20 years after onset. Approximately 30% of T1D and 40% of T2D patients develop diabetic nephropathy, partly due to the often-unclear onset of T2D. Diabetes-related structural and functional kidney changes result in proteinuria, hypertension, and progressive kidney function decline, hallmarks of diabetic nephropathy.

The primary pathological lesions of diabetic nephropathy are diffuse mesangial cell expansion, GBM thickening, and arteriolar hyalinization. However, virtually all kidney compartments are affected. Diabetic nephropathy progression typically correlates with increasing albuminuria, from normal levels to microalbuminuria (moderately increased) and then macroalbuminuria (severely increased). Aggressive treatment can partially reverse this progression.

The glomerular filtration barrier, composed of capillary endothelial cells, GBM, and podocytes, is crucial for kidney function. The GBM, significantly thicker than capillaries elsewhere, is highly fenestrated and composed of type IV collagen and negatively charged proteoglycans, acting as a selective filter. Nephrin, a key GBM component, maintains slit diaphragm integrity, preventing protein loss in urine. Reduced nephrin expression is an early event in diabetic nephropathy. Synaptopodin, another podocyte protein, is also downregulated in DKD. MCP-1 further reduces nephrin and synaptopodin expression and is linked to albuminuria.

Hyperfiltration, an early pathological change in diabetic nephropathy, involves both glomeruli and tubules, partially mediated by hyperglycemia-induced upregulation of SGLT1 and SGLT2 and decreased vascular resistance. Hyperfiltration reduces sodium concentration at the macula densa, increasing dietary salt sensitivity and worsening hypertension. Increased tubular hyperfiltration contributes to nephron enlargement and cellular hypertrophy. Dietary protein sources also play a role; animal protein promotes hyperfiltration and insulin resistance, while plant protein enhances insulin sensitivity, suggesting plant protein prioritization for diabetic patients.

Vascular regulation also mediates hyperfiltration, with prostaglandins and atrial natriuretic peptides reducing arteriolar resistance. Endothelial dysfunction is linked to glomerular hyperfiltration, with increased endothelin-1 levels in T2D patients with proteinuria.

Histopathological Classification of Diabetic Nephropathy

Abnormal renal pathology is evident even before microalbuminuria onset. Light microscopy reveals characteristic lesions: thickened glomerular and tubular basement membranes, diffuse mesangial expansion, and arteriolar hyalinosis.

The pathological classification of diabetic nephropathy includes:

• Class I: GBM thickening
• Class IIa: Mild mesangial expansion
• Class IIb: Severe mesangial expansion
• Class III: Nodular glomerulosclerosis (Kimmelstiel-Wilson nodules)
• Class IV: Advanced diabetic nephropathy with over 50% glomerulosclerosis and associated lesions

Tubulointerstitial inflammation/atrophy and vascular lesions are scored (0-3 scales). Additional findings include arteriosclerosis, exudative lesions, and interstitial fibrosis. Mesangial expansion limits capillary filtration capacity, contributing to GFR decline.

History and Physical Examination in Diabetic Nephropathy

A prolonged duration of diabetes mellitus, poor glycemic control, and uncontrolled hypertension are major risk factors for diabetic nephropathy. Other risk factors include obesity, smoking, hyperlipidemia, and family history. Patients may also present with peripheral vascular disease, coronary artery disease, and diabetic retinopathy. Diabetic retinopathy has a particularly strong correlation with diabetic nephropathy.

Early stages of diabetic nephropathy are often asymptomatic, detected through screening revealing proteinuria (30-300 mg/g creatinine). As the disease progresses, patients may experience fatigue, foamy urine (indicative of significant proteinuria), and pedal edema due to hypoalbuminemia and nephrotic syndrome.

General diabetes mellitus findings may include:

• Fatigue
• Dizziness
• Polydipsia and polyuria
• Polyphagia
• Blurred vision
• Tingling or numbness
• Peripheral neuropathy
• Foot ulcers
• Delayed wound healing
• Frequent infections
• Nausea, vomiting, and abdominal pain
• Acanthosis Nigricans (T2D)
• Unexplained weight loss (T1D)

Evaluation and Diagnosis Diabetic Nephropathy

Proteinuria Assessment for Diagnosis

Proteinuria is a hallmark of diabetic nephropathy. Diagnosis diabetic nephropathy in T2D is more complex than in T1D due to the uncertain onset of T2D. History and physical exam are crucial. T1D patients should be screened for proteinuria within 5 years of diagnosis, while T2D patients should be screened at diagnosis and annually. Increased proteinuria indicates declining kidney function requiring aggressive management.

Diabetic nephropathy is diagnosed by persistent albuminuria on 2+ occasions, 3+ months apart, using early morning urine samples. Persistent albuminuria is ≥300 mg/d. Moderately increased albuminuria (early diabetic nephropathy) is 30-300 mg/24 hours, or a spot urine-to-creatinine ratio of 20-200 mg/g or 20-200 µg/min. Severe albuminuria is >300 mg/day.

Novel Urinary Biomarkers for Early Diagnosis

Given the limitations of creatinine and albuminuria as late-stage markers, research is exploring novel biomarkers for earlier diagnosis diabetic nephropathy, particularly markers of tubulointerstitial injury. Non-albuminuric proteinuria is strongly associated with DKD, and proximal tubular damage may precede glomerular damage.

Neutrophil gelatinase-associated lipocalin (NGAL) and kidney injury molecule-1 (KIM-1) are elevated in early diabetic nephropathy, even before albuminuria, and correlate with GFR decline. Urinary KIM-1 indicates proximal tubule damage, while NGAL is associated with loop of Henle and distal tubule damage. NGAL is also an early marker of acute kidney injury (AKI), detectable hours after insult, before creatinine changes. Urinary NGAL also appears before albuminuria.

NGAL, KIM-1, and periostin are among the most studied biomarkers. Studies show sensitivities and specificities for NGAL (76%, 55%), KIM-1 (63%, 90%), and periostin (80%, 66%). While not yet widely available clinically, these biomarkers are becoming more established, and combinations may enhance early diagnosis diabetic nephropathy. The table below lists potential biomarkers studied over the past decade.

Table. Potential Biomarkers for Diabetic Nephropathy.

Table reference [42]

Treatment and Management Strategies

Diabetic nephropathy management focuses on four key areas: cardiovascular risk reduction, glycemic control, blood pressure (BP) control, and renin-angiotensin system (RAS) inhibition. Modifying risk factors like smoking and optimizing lipid control are crucial.

Glycemic Control in DKD Management

Intensive glycemic control is most effective when initiated early, before diabetic complications arise. Early intensive glycemic control is highly recommended. The UKPDS demonstrated that early glycemic control in T2D patients (HbA1c of 7.0%) led to sustained microvascular benefits and lower mortality, even after HbA1c levels converged between groups. The DCCT showed similar results in T1D patients. This “legacy effect” highlights the long-term benefits of early glucose-lowering therapy, especially keeping HbA1c <6.5% in the first year of diagnosis. However, long-term intensive glucose control may not always be beneficial, with some studies showing worse outcomes due to hypoglycemia. KDOQI and KDIGO guidelines recommend an HbA1c goal of ~7.0% to mitigate microvascular complications.

Glycated albumin and fructosamine are less common glycemic control measures and are less validated. HbA1c, while the most accurate long-term measure, may not reflect hypoglycemia or severe hyperglycemia episodes, more prevalent in CKD. NKF-KDOQI guidelines suggest an HbA1c goal of ~7.0%, but individualized targets are recommended based on clinical condition.

RAAS Inhibition for Blood Pressure and Renoprotection

KDIGO guidelines recommend a BP target of <120/80 mm Hg for diabetic individuals, individualized based on patient factors. ACEIs or ARBs are recommended for all hypertensive diabetic patients unless contraindicated, titrated to the highest tolerated dose. Their use in albuminuria without hypertension is less studied but may be considered individually. Kidney transplant recipients with diabetes and hypertension should also receive RAAS inhibition. Evidence supports their use in hypertensive dialysis patients; discontinuation is linked to higher cardiovascular death, myocardial infarction, and stroke rates. KDIGO recommends dietary compliance and potassium binders to manage ACEI/ARB-associated hyperkalemia.

Studies like RENAAL and IDNT demonstrate ARB benefits in delaying kidney disease progression. UKPDS highlighted BP control’s positive impact on diabetes complications. HOPE, LIFE, and ALLHAT trials confirmed ACEI benefits in slowing CKD progression in individuals with eGFR >60 mL/min/1.73m2. IRMA2 showed ARB benefits in preventing proteinuria in microalbuminuria. Studies in T1D and overt proteinuria show ACEIs slow diabetic nephropathy progression, with IDNT and RENAAL showing similar benefits in T2D. RAAS-blocking medications slow diabetic nephropathy progression, independent of BP effects. However, multiple RAS-blocking agents are not recommended due to adverse outcomes like acute renal failure. RAAS inhibition is discouraged in diabetic patients without hypertension or albuminuria.

A RENAAL trial post hoc analysis suggested uric acid level reduction in the losartan group as a renoprotective mechanism. Uric acid–lowering agent studies have mixed results. In AKI, ACEI/ARB therapy is often temporarily discontinued. However, a retrospective study indicated lower mortality with continued ACEI/ARB therapy, despite higher renal-related hospitalizations. Benefits of continuing ACEI/ARB therapy in advanced CKD remain unclear. The STOP-ACEI trial found no significant outcome difference between continued vs. discontinued ACEI/ARB therapy in diabetic nephropathy patients with eGFR <30 mL/min/1.73m2.

Metformin and GLP-1 Receptor Agonists in Diabetes Management with CKD

KDIGO and ADA guidelines recommend metformin with diet as first-line T2D treatment with CKD and eGFR >30 mL/min/1.73m2. Metformin has demonstrated benefits in CKD progression, cardiovascular outcomes, and mortality. However, metformin initiation is not recommended for eGFR <45 mL/min/1.73m2 due to lactic acidosis risk. Dosage should be halved for eGFR 45-60 mL/min/1.73m2. Metformin should be withheld during inpatient admissions. It may also reduce vitamin B12 and folate levels, requiring monitoring and supplementation.

The European Society of Cardiology recommends GLP-1 receptor agonists (GLP1RAs) or SGLT2 inhibitors (SGLT2Is) as first-line agents for high cardiovascular risk patients. KDIGO advises GLP1RAs when glycemic control is not achieved with metformin or SGLT2Is. GLP1RAs should be titrated gradually and avoided with dipeptidyl peptidase-4 inhibitors. GLP1RAs and SGLT2Is are supported by robust evidence for improving outcomes across diverse patient populations.

Mineralocorticoid Receptor Antagonists

Mineralocorticoid receptor activation is linked to inflammation, fibrosis, and adverse hemodynamic remodeling in cardiac and renal diseases. Spironolactone and eplerenone, steroidal mineralocorticoid antagonists, are effective, especially in heart failure with reduced ejection fraction, and reduce proteinuria in CKD. Spironolactone has a high hyperkalemia and gynecomastia incidence, limiting use. Eplerenone has lower hyperkalemia risk but less BP-lowering effect. Historically avoided in ESRD, randomized controlled trials show improved cardiac outcomes with low-dose spironolactone in this population.

Finerenone, a selective, nonsteroidal mineralocorticoid antagonist, is approved for CKD associated with T2D. It reduces albuminuria and improves renal and cardiovascular outcomes in CKD and T2D, as shown in FIDELITY-DKD, FIGARO-DKD, and FINEARTS-HF trials. Finerenone is effective in patients with and without reduced ejection fraction and may prevent or delay heart failure onset in T2D and CKD. The ARTS trial showed finerenone is at least as effective as spironolactone, with lower hyperkalemia and adverse effects. It improves albuminuria independently of BP or GFR changes. Esaxerenone, similar to finerenone, is used in Japan and other countries and reduces albuminuria in T2D, but is not FDA-approved.

SGLT2 Inhibitors: Renoprotective and Cardioprotective Agents

SGLT2Is reduce glucose reabsorption in the proximal tubule, increasing glucosuria, reducing capillary hypertension, albuminuria, GFR loss, and nephron metabolic demand. They also mitigate macula densa sodium hypersensitivity, decreasing glomerular hypertension and energy expenditure. They stimulate hypoxia-inducible factors (HIFs), enhancing erythropoietin production. Effective in both T2D and non-T2D patients via glucose-dependent and -independent mechanisms, SGLT2Is generally do not cause hypoglycemia and increase glucagon secretion, stimulating hepatic gluconeogenesis.

SGLT2Is promote a metabolic shift from carbohydrate to lipid utilization, reducing visceral and subcutaneous fat and overall weight. Released free fatty acids convert to ketone bodies, an energy source for renal and cardiac cells. Another renoprotective mechanism is blocking glucose reabsorption, reducing sodium, chloride, and free water absorption, mitigating glomerular hyperfiltration and preserving GFR. Cardiovascular outcome trials (EMPA-REG, CANVAS, DECLARE-TIMI) show SGLT2Is’ positive kidney effects, including albuminuria reduction and adverse renal event reduction, leading to interest in primary renal outcomes as endpoints. DAPA-CKD trial highlighted SGLT2Is’ benefits on renal and cardiovascular outcomes in non-T2D patients. The CREDENCE trial, comparing SGLT2Is to placebo in T2D and albuminuric CKD, was stopped early due to a 30% relative risk reduction in renal and cardiovascular events in the treatment group.

Additional and Emerging Treatments

Shenkang, a traditional Chinese medicine injectable mixture, has shown in animal studies to reduce fibrosis and increase nephrin expression. Isoquercitrin, a natural plant compound, shows antidiabetic potential by inhibiting the SGLT2 pathway and reducing blood sugar in animal models.

Renal Replacement Therapy

Once ESRD develops (eGFR 10-15 mL/min/1.73m2), renal replacement therapy is needed. Options include peritoneal dialysis, hemodialysis, and renal transplantation. Renal transplant is preferred for patients with good functional status, referral to a transplant center is recommended when GFR declines to ~20 mL/min/1.73m2. 47% of patients on renal transplant lists also have diabetes, and this percentage is expected to rise. Simultaneous pancreas and kidney transplants are becoming more common with excellent outcomes, showing better outcomes for diabetic patients receiving both organs versus kidney transplant alone. However, DKD can recur in transplanted kidneys in ~7% of cases, with tacrolimus use particularly associated with recurrence.

Differential Diagnosis

Several conditions can mimic diabetic nephropathy, differentiated based on patient history and lab parameters:

• Multiple myeloma
• Amyloidosis
• Membranous nephropathy
• Renal artery stenosis
• Tubulointerstitial nephritis
• Hypertensive nephropathy
• Focal segmental glomerulosclerosis
• Infection-related glomerulonephritis

Toxicity and Adverse Effect Management of Diabetes Medications in CKD

Impact of CKD on Diabetes Medication Management

Kidneys are vital for insulin clearance. In CKD, decreased GFR prolongs insulin’s presence, requiring dose reduction to prevent hypoglycemia. This principle applies to most oral antidiabetic medications cleared by kidneys. Metformin is contraindicated in eGFR <30 mL/min/1.73m2 due to lactic acidosis risk. Caution is advised for most oral antidiabetic medications when eGFR <45 mL/min/1.73m2. Diabetic nephropathy patients are at increased AKI risk and require monitoring when using nephrotoxic medications like NSAIDs and intravenous contrast.

Prognosis of Diabetic Nephropathy

Diabetic nephropathy is associated with high morbidity and mortality. Microalbuminuria is an independent risk factor for cardiovascular mortality, and most patients ultimately die from ESRD. Diabetic retinopathy is commonly associated with diabetic nephropathy, further worsening prognosis.

Deterrence and Patient Education

• Protein intake: ~0.8 g/kg body weight in diabetes and CKD; 1.0-1.2 g/kg for dialysis patients.
• Plant protein is associated with lower CKD and proteinuria progression risk compared to animal protein.
• HbA1c target: <7.0%, individualized treatment plans.
• BP target: <120/80 mm Hg.
• Sodium intake limit: <2.3 g/d in diabetes and eGFR <30 mL/min/1.73m2.
• Avoid nephrotoxic agents and drugs.
• Regular urine albumin level monitoring.
• Home blood glucose monitoring can delay renal dysfunction progression.

Pearls and Future Directions

The field of diabetic nephropathy is rapidly advancing, offering hope for future treatments. Research into polyol pathway inhibitors, antioxidants, vasoprotective agents, new anti-inflammatory drugs, and microRNA regulation is promising. MicroRNAs are noncoding RNAs involved in diabetic nephropathy pathogenesis, influencing inflammation, oxidative stress, apoptosis, and vascular cell function. HIF prolyl hydroxylase inhibitors, used for CKD anemia, are also under investigation. These may prevent tubulointerstitial injury and renal fibrosis.

Enhancing Healthcare Team Outcomes

Diabetic nephropathy is a severe, chronic condition with high morbidity and mortality. Prevention and early intervention are crucial. Care requires a multidisciplinary team: internal medicine specialists, hospitalists, endocrinologists, nephrologists, cardiologists, and pathologists. Patient-centered care involves physicians, advanced practice providers, nurses, pharmacists, and dietitians. Dietitians are vital for diet planning to ensure adequate protein and optimal blood sugar levels.

Healthcare providers need clinical skills to diagnose, evaluate, and treat effectively, including lab result interpretation, complication recognition, and medication management. Ethical considerations are key in treatment decisions and respecting patient autonomy. Clear interprofessional team responsibilities and effective communication are essential for collaboration and optimized patient care. Care coordination is crucial for seamless patient care from diagnosis diabetic nephropathy to treatment and follow-up, minimizing errors, reducing delays, and enhancing patient safety, leading to improved outcomes and patient-centered care.

Review Questions

Access free multiple choice questions on this topic.

References

1.Rabkin R. Diabetic nephropathy. Clin Cornerstone. 2003;5(2):1-11. [PubMed: 12800476]

2.Mottl AK, Alicic R, Argyropoulos C, Brosius FC, Mauer M, Molitch M, Nelson RG, Perreault L, Nicholas SB. KDOQI US Commentary on the KDIGO 2020 Clinical Practice Guideline for Diabetes Management in CKD. Am J Kidney Dis. 2022 Apr;79(4):457-479. [PMC free article: PMC9740752] [PubMed: 35144840]

3.Lin DW, Yang TM, Ho C, Shih YH, Lin CL, Hsu YC. Targeting Macrophages: Therapeutic Approaches in Diabetic Kidney Disease. Int J Mol Sci. 2024 Apr 15;25(8) [PMC free article: PMC11050450] [PubMed: 38673935]

4.Klessens CQF, Zandbergen M, Wolterbeek R, Bruijn JA, Rabelink TJ, Bajema IM, IJpelaar DHT. Macrophages in diabetic nephropathy in patients with type 2 diabetes. Nephrol Dial Transplant. 2017 Aug 01;32(8):1322-1329. [PubMed: 27416772]

5.Yang J, Liu Z. Mechanistic Pathogenesis of Endothelial Dysfunction in Diabetic Nephropathy and Retinopathy. Front Endocrinol (Lausanne). 2022;13:816400. [PMC free article: PMC9174994] [PubMed: 35692405]

6.Xu C, Ha X, Yang S, Tian X, Jiang H. Advances in understanding and treating diabetic kidney disease: focus on tubulointerstitial inflammation mechanisms. Front Endocrinol (Lausanne). 2023;14:1232790. [PMC free article: PMC10583558] [PubMed: 37859992]

7.Rayego-Mateos S, Morgado-Pascual JL, Opazo-Ríos L, Guerrero-Hue M, García-Caballero C, Vázquez-Carballo C, Mas S, Sanz AB, Herencia C, Mezzano S, Gómez-Guerrero C, Moreno JA, Egido J. Pathogenic Pathways and Therapeutic Approaches Targeting Inflammation in Diabetic Nephropathy. Int J Mol Sci. 2020 May 27;21(11) [PMC free article: PMC7312633] [PubMed: 32471207]

8.Li X, Zhang Y, Xing X, Li M, Liu Y, Xu A, Zhang J. Podocyte injury of diabetic nephropathy: Novel mechanism discovery and therapeutic prospects. Biomed Pharmacother. 2023 Dec;168:115670. [PubMed: 37837883]

9.Barutta F, Bellini S, Gruden G. Mechanisms of podocyte injury and implications for diabetic nephropathy. Clin Sci (Lond). 2022 Apr 14;136(7):493-520. [PMC free article: PMC9008595] [PubMed: 35415751]

10.Ising C, Koehler S, Brähler S, Merkwirth C, Höhne M, Baris OR, Hagmann H, Kann M, Fabretti F, Dafinger C, Bloch W, Schermer B, Linkermann A, Brüning JC, Kurschat CE, Müller RU, Wiesner RJ, Langer T, Benzing T, Brinkkoetter PT. Inhibition of insulin/IGF-1 receptor signaling protects from mitochondria-mediated kidney failure. EMBO Mol Med. 2015 Mar;7(3):275-87. [PMC free article: PMC4364945] [PubMed: 25643582]

11.Vallon V, Nakagawa T. Renal Tubular Handling of Glucose and Fructose in Health and Disease. Compr Physiol. 2021 Dec 29;12(1):2995-3044. [PMC free article: PMC9832976] [PubMed: 34964123]

12.Jalal DI, Maahs DM, Hovind P, Nakagawa T. Uric acid as a mediator of diabetic nephropathy. Semin Nephrol. 2011 Sep;31(5):459-65. [PMC free article: PMC3197214] [PubMed: 22000654]

13.Ma X, Ma J, Leng T, Yuan Z, Hu T, Liu Q, Shen T. Advances in oxidative stress in pathogenesis of diabetic kidney disease and efficacy of TCM intervention. Ren Fail. 2023 Dec;45(1):2146512. [PMC free article: PMC9930779] [PubMed: 36762989]

14.Zhou X, Liu Z, Ying K, Wang H, Liu P, Ji X, Chi T, Zou L, Wang S, He Z. WJ-39, an Aldose Reductase Inhibitor, Ameliorates Renal Lesions in Diabetic Nephropathy by Activating Nrf2 Signaling. Oxid Med Cell Longev. 2020;2020:7950457. [PMC free article: PMC7277034] [PubMed: 32566101]

15.Daneshpajouhnejad P, Kopp JB, Winkler CA, Rosenberg AZ. The evolving story of apolipoprotein L1 nephropathy: the end of the beginning. Nat Rev Nephrol. 2022 May;18(5):307-320. [PMC free article: PMC8877744] [PubMed: 35217848]

16.Ha SK. ACE insertion/deletion polymorphism and diabetic nephropathy: clinical implications of genetic information. J Diabetes Res. 2014;2014:846068. [PMC free article: PMC4284953] [PubMed: 25587546]

17.Bertoncello N, Moreira RP, Arita DY, Aragão DS, Watanabe IK, Dantas PS, Santos R, Mattar-Rosa R, Yokota R, Cunha TS, Casarini DE. Diabetic Nephropathy Induced by Increased Ace Gene Dosage Is Associated with High Renal Levels of Angiotensin (1-7) and Bradykinin. J Diabetes Res. 2015;2015:674047. [PMC free article: PMC4579315] [PubMed: 26442284]

18.Wang Y, Zhang J, Zhao Y, Wang S, Zhang J, Han Q, Zhang R, Guo R, Li H, Li L, Wang T, Tang X, He C, Teng G, Gu W, Liu F. COL4A3 Gene Variants and Diabetic Kidney Disease in MODY. Clin J Am Soc Nephrol. 2018 Aug 07;13(8):1162-1171. [PMC free article: PMC6086715] [PubMed: 30012629]

19.Gui H, Chen X, Ye L, Ma H. Seven basement membrane-specific expressed genes are considered potential biomarkers for the diagnosis and treatment of diabetic nephropathy. Acta Diabetol. 2023 Apr;60(4):493-505. [PubMed: 36627452]

20.Li X, Lu L, Hou W, Huang T, Chen X, Qi J, Zhao Y, Zhu M. Epigenetics in the pathogenesis of diabetic nephropathy. Acta Biochim Biophys Sin (Shanghai). 2022 Jan 25;54(2):163-172. [PMC free article: PMC9909329] [PubMed: 35130617]

21.Qu Z, Wang B, Jin Y, Xiao Q, Zhao Y, Zhao D, Yang L. Shenkang protects renal function in diabetic rats by preserving nephrin expression. BMC Complement Med Ther. 2023 Jul 17;23(1):244. [PMC free article: PMC10353195] [PubMed: 37460931]

22.Umanath K, Lewis JB. Update on Diabetic Nephropathy: Core Curriculum 2018. Am J Kidney Dis. 2018 Jun;71(6):884-895. [PubMed: 29398179]

23.Młynarska E, Buławska D, Czarnik W, Hajdys J, Majchrowicz G, Prusinowski F, Stabrawa M, Rysz J, Franczyk B. Novel Insights into Diabetic Kidney Disease. Int J Mol Sci. 2024 Sep 23;25(18) [PMC free article: PMC11432709] [PubMed: 39337706]

24.Satirapoj B, Adler SG. Comprehensive approach to diabetic nephropathy. Kidney Res Clin Pract. 2014 Sep;33(3):121-31. [PMC free article: PMC4714158] [PubMed: 26894033]

25.Clos-Garcia M, Ahluwalia TS, Winther SA, Henriksen P, Ali M, Fan Y, Stankevic E, Lyu L, Vogt JK, Hansen T, Legido-Quigley C, Rossing P, Pedersen O. Multiomics signatures of type 1 diabetes with and without albuminuria. Front Endocrinol (Lausanne). 2022;13:1015557. [PMC free article: PMC9755599] [PubMed: 36531462]

26.Tarabra E, Giunti S, Barutta F, Salvidio G, Burt D, Deferrari G, Gambino R, Vergola D, Pinach S, Perin PC, Camussi G, Gruden G. Effect of the monocyte chemoattractant protein-1/CC chemokine receptor 2 system on nephrin expression in streptozotocin-treated mice and human cultured podocytes. Diabetes. 2009 Sep;58(9):2109-18. [PMC free article: PMC2731530] [PubMed: 19587356]

27.Yang Y, Xu G. Update on Pathogenesis of Glomerular Hyperfiltration in Early Diabetic Kidney Disease. Front Endocrinol (Lausanne). 2022;13:872918. [PMC free article: PMC9161673] [PubMed: 35663316]

28.Vallon V, Verma S. Effects of SGLT2 Inhibitors on Kidney and Cardiovascular Function. Annu Rev Physiol. 2021 Feb 10;83:503-528. [PMC free article: PMC8017904] [PubMed: 33197224]

29.Adeva-Andany MM, Fernández-Fernández C, Carneiro-Freire N, Vila-Altesor M, Ameneiros-Rodríguez E. The differential effect of animal versus vegetable dietary protein on the clinical manifestations of diabetic kidney disease in humans. Clin Nutr ESPEN. 2022 Apr;48:21-35. [PubMed: 35331493]

30.Liu C, Li Q, Feng X, Zhu J, Li Q. Deterioration of diabetic nephropathy via stimulating secretion of cytokines by atrial natriuretic peptide. BMC Endocr Disord. 2021 Oct 18;21(1):204. [PMC free article: PMC8525036] [PubMed: 34663293]

31.Jung C, Rafnsson A, Brismar K, Pernow J. Endothelial progenitor cells in relation to endothelin-1 and endothelin receptor blockade: a randomized, controlled trial. Int J Cardiol. 2013 Sep 30;168(2):1017-22. [PubMed: 23168014]

32.Goldney J, Sargeant JA, Davies MJ. Incretins and microvascular complications of diabetes: neuropathy, nephropathy, retinopathy and microangiopathy. Diabetologia. 2023 Oct;66(10):1832-1845. [PMC free article: PMC10474214] [PubMed: 37597048]

33.Wang Y, Shao T, Wang J, Huang X, Deng X, Cao Y, Zhou M, Zhao C. An update on potential biomarkers for diagnosing diabetic foot ulcer at early stage. Biomed Pharmacother. 2021 Jan;133:110991. [PubMed: 33227713]

34.Rehman ZU, Khan J, Noordin S. Diabetic Foot Ulcers: Contemporary Assessment And Management. J Pak Med Assoc. 2023 Jul;73(7):1480-1487. [PubMed: 37469062]

35.Radu AM, Carsote M, Dumitrascu MC, Sandru F. Acanthosis Nigricans: Pointer of Endocrine Entities. Diagnostics (Basel). 2022 Oct 17;12(10) [PMC free article: PMC9600076] [PubMed: 36292208]

36.Szabóová E, Lisovszki A, Fatľová E, Kolarčik P, Szabó P, Molnár T. Prevalence of Microalbuminuria and Its Association with Subclinical Carotid Atherosclerosis in Middle Aged, Nondiabetic, Low to Moderate Cardiovascular Risk Individuals with or without Hypertension. Diagnostics (Basel). 2021 Sep 19;11(9) [PMC free article: PMC8464680] [PubMed: 34574057]

37.Singh A, Satchell SC. Microalbuminuria: causes and implications. Pediatr Nephrol. 2011 Nov;26(11):1957-65. [PMC free article: PMC3178015] [PubMed: 21301888]

38.Hwang S, Park J, Kim J, Jang HR, Kwon GY, Huh W, Kim YG, Kim DJ, Oh HY, Lee JE. Tissue expression of tubular injury markers is associated with renal function decline in diabetic nephropathy. J Diabetes Complications. 2017 Dec;31(12):1704-1709. [PubMed: 29037450]

39.Zhou Y, Zhang Y, Chen J, Wang T, Li H, Wu F, Shang J, Zhao Z. Diagnostic value of α1-MG and URBP in early diabetic renal impairment. Front Physiol. 2023;14:1173982. [PMC free article: PMC10621041] [PubMed: 37929213]

40.Haase M, Devarajan P, Haase-Fielitz A, Bellomo R, Cruz DN, Wagener G, Krawczeski CD, Koyner JL, Murray P, Zappitelli M, Goldstein SL, Makris K, Ronco C, Martensson J, Martling CR, Venge P, Siew E, Ware LB, Ikizler TA, Mertens PR. The outcome of neutrophil gelatinase-associated lipocalin-positive subclinical acute kidney injury: a multicenter pooled analysis of prospective studies. J Am Coll Cardiol. 2011 Apr 26;57(17):1752-61. [PMC free article: PMC4866647] [PubMed: 21511111]

41.Varatharajan S, Jain V, Pyati AK, Neeradi C, Reddy KS, Pallavali JR, Pandiyaraj IP, Gaur A. Neutrophil gelatinase-associated lipocalin, kidney injury molecule-1, and periostin: Novel urinary biomarkers in diabetic nephropathy. World J Nephrol. 2024 Dec 25;13(4):98880. [PMC free article: PMC11572651] [PubMed: 39723350]

42.Khanijou V, Zafari N, Coughlan MT, MacIsaac RJ, Ekinci EI. Review of potential biomarkers of inflammation and kidney injury in diabetic kidney disease. Diabetes Metab Res Rev. 2022 Sep;38(6):e3556. [PMC free article: PMC9541229] [PubMed: 35708187]

43.Zhu H, Li L, Liu S, Li J. Smoking and diabetic nephropathy: An updated systematic review and meta-analysis. J Diabetes Investig. 2024 Dec 27; [PubMed: 39728025]

44.Altunkaynak HO, Karaismailoglu E, Massy ZA. The Ability of AST-120 to Lower the Serum Indoxyl Sulfate Level Improves Renal Outcomes and the Lipid Profile in Diabetic and Nondiabetic Animal Models of Chronic Kidney Disease: A Meta-Analysis. Toxins (Basel). 2024 Dec 16;16(12) [PMC free article: PMC11679735] [PubMed: 39728802]

45.Han YZ, Du BX, Zhu XY, Wang YZ, Zheng HJ, Liu WJ. Lipid metabolism disorder in diabetic kidney disease. Front Endocrinol (Lausanne). 2024;15:1336402. [PMC free article: PMC11089115] [PubMed: 38742197]

46.Laiteerapong N, Ham SA, Gao Y, Moffet HH, Liu JY, Huang ES, Karter AJ. The Legacy Effect in Type 2 Diabetes: Impact of Early Glycemic Control on Future Complications (The Diabetes & Aging Study). Diabetes Care. 2019 Mar;42(3):416-426. [PMC free article: PMC6385699] [PubMed: 30104301]

47.Holman RR, Paul SK, Bethel MA, Matthews DR, Neil HA. 10-year follow-up of intensive glucose control in type 2 diabetes. N Engl J Med. 2008 Oct 09;359(15):1577-89. [PubMed: 18784090]

48.Genuth S, Eastman R, Kahn R, Klein R, Lachin J, Lebovitz H, Nathan D, Vinicor F., American Diabetes Association. Implications of the United kingdom prospective diabetes study. Diabetes Care. 2003 Jan;26 Suppl 1:S28-32. [PubMed: 12502617]

49.de Boer IH, Rue TC, Cleary PA, Lachin JM, Molitch ME, Steffes MW, Sun W, Zinman B, Brunzell JD, Diabetes Control and Complications Trial/Epidemiology of Diabetes Interventions and Complications Study Research Group. White NH, Danis RP, Davis MD, Hainsworth D, Hubbard LD, Nathan DM. Long-term renal outcomes of patients with type 1 diabetes mellitus and microalbuminuria: an analysis of the Diabetes Control and Complications Trial/Epidemiology of Diabetes Interventions and Complications cohort. Arch Intern Med. 2011 Mar 14;171(5):412-20. [PMC free article: PMC3085024] [PubMed: 21403038]

50.Galindo RJ, Beck RW, Scioscia MF, Umpierrez GE, Tuttle KR. Glycemic Monitoring and Management in Advanced Chronic Kidney Disease. Endocr Rev. 2020 Oct 01;41(5):756-74. [PMC free article: PMC7366347] [PubMed: 32455432]

51.Brenner BM, Cooper ME, de Zeeuw D, Keane WF, Mitch WE, Parving HH, Remuzzi G, Snapinn SM, Zhang Z, Shahinfar S., RENAAL Study Investigators. Effects of losartan on renal and cardiovascular outcomes in patients with type 2 diabetes and nephropathy. N Engl J Med. 2001 Sep 20;345(12):861-9. [PubMed: 11565518]

52.Lewis EJ, Hunsicker LG, Clarke WR, Berl T, Pohl MA, Lewis JB, Ritz E, Atkins RC, Rohde R, Raz I., Collaborative Study Group. Renoprotective effect of the angiotensin-receptor antagonist irbesartan in patients with nephropathy due to type 2 diabetes. N Engl J Med. 2001 Sep 20;345(12):851-60. [PubMed: 11565517]

53.Armstrong C., Joint National Committee. JNC8 guidelines for the management of hypertension in adults. Am Fam Physician. 2014 Oct 01;90(7):503-4. [PubMed: 25369633]

54.Parving HH, Lehnert H, Bröchner-Mortensen J, Gomis R, Andersen S, Arner P., Irbesartan in Patients with Type 2 Diabetes and Microalbuminuria Study Group. The effect of irbesartan on the development of diabetic nephropathy in patients with type 2 diabetes. N Engl J Med. 2001 Sep 20;345(12):870-8. [PubMed: 11565519]

55.Brar S, Ye F, James MT, Hemmelgarn B, Klarenbach S, Pannu N., Interdisciplinary Chronic Disease Collaboration. Association of Angiotensin-Converting Enzyme Inhibitor or Angiotensin Receptor Blocker Use With Outcomes After Acute Kidney Injury. JAMA Intern Med. 2018 Dec 01;178(12):1681-1690. [PMC free article: PMC6583606] [PubMed: 30422153]

56.Bhandari S, Mehta S, Khwaja A, Cleland JGF, Ives N, Brettell E, Chadburn M, Cockwell P., STOP ACEi Trial Investigators. Renin-Angiotensin System Inhibition in Advanced Chronic Kidney Disease. N Engl J Med. 2022 Dec 01;387(22):2021-2032. [PubMed: 36326117]

57.de Jager J, Kooy A, Lehert P, Wulffelé MG, van der Kolk J, Bets D, Verburg J, Donker AJ, Stehouwer CD. Long term treatment with metformin in patients with type 2 diabetes and risk of vitamin B-12 deficiency: randomised placebo controlled trial. BMJ. 2010 May 20;340:c2181. [PMC free article: PMC2874129] [PubMed: 20488910]

58.Cosentino F, Grant PJ, Aboyans V, Bailey CJ, Ceriello A, Delgado V, Federici M, Filippatos G, Grobbee DE, Hansen TB, Huikuri HV, Johansson I, Jüni P, Lettino M, Marx N, Mellbin LG, Östgren CJ, Rocca B, Roffi M, Sattar N, Seferović PM, Sousa-Uva M, Valensi P, Wheeler DC., ESC Scientific Document Group. 2019 ESC Guidelines on diabetes, pre-diabetes, and cardiovascular diseases developed in collaboration with the EASD. Eur Heart J. 2020 Jan 07;41(2):255-323. [PubMed: 31497854]

59.Kintscher U, Bakris GL, Kolkhof P. Novel non-steroidal mineralocorticoid receptor antagonists in cardiorenal disease. Br J Pharmacol. 2022 Jul;179(13):3220-3234. [PubMed: 34811750]

60.Bolignano D, Palmer SC, Navaneethan SD, Strippoli GF. Aldosterone antagonists for preventing the progression of chronic kidney disease. Cochrane Database Syst Rev. 2014 Apr 29;(4):CD007004. [PubMed: 24782282]

61.Agarwal R, Kolkhof P, Bakris G, Bauersachs J, Haller H, Wada T, Zannad F. Steroidal and non-steroidal mineralocorticoid receptor antagonists in cardiorenal medicine. Eur Heart J. 2021 Jan 07;42(2):152-161. [PMC free article: PMC7813624] [PubMed: 33099609]

62.Agarwal A, Cheung AK. Mineralocorticoid Receptor Antagonists in ESKD. Clin J Am Soc Nephrol. 2020 Jul 01;15(7):1047-1049. [PMC free article: PMC7341785] [PubMed: 32269029]

63.Bakris GL, Agarwal R, Chan JC, Cooper ME, Gansevoort RT, Haller H, Remuzzi G, Rossing P, Schmieder RE, Nowack C, Kolkhof P, Joseph A, Pieper A, Kimmeskamp-Kirschbaum N, Ruilope LM., Mineralocorticoid Receptor Antagonist Tolerability Study–Diabetic Nephropathy (ARTS-DN) Study Group. Effect of Finerenone on Albuminuria in Patients With Diabetic Nephropathy: A Randomized Clinical Trial. JAMA. 2015 Sep 01;314(9):884-94. [PubMed: 26325557]

64.Bakris GL, Agarwal R, Anker SD, Pitt B, Ruilope LM, Rossing P, Kolkhof P, Nowack C, Schloemer P, Joseph A, Filippatos G., FIDELIO-DKD Investigators. Effect of Finerenone on Chronic Kidney Disease Outcomes in Type 2 Diabetes. N Engl J Med. 2020 Dec 03;383(23):2219-2229. [PubMed: 33264825]

65.Filippatos G, Anker SD, Agarwal R, Ruilope LM, Rossing P, Bakris GL, Tasto C, Joseph A, Kolkhof P, Lage A, Pitt B., FIGARO-DKD Investigators. Finerenone Reduces Risk of Incident Heart Failure in Patients With Chronic Kidney Disease and Type 2 Diabetes: Analyses From the FIGARO-DKD Trial. Circulation. 2022 Feb 08;145(6):437-447. [PMC free article: PMC8812430] [PubMed: 34775784]

66.Vallon V, Thomson SC. Targeting renal glucose reabsorption to treat hyperglycaemia: the pleiotropic effects of SGLT2 inhibition. Diabetologia. 2017 Feb;60(2):215-225. [PMC free article: PMC5884445] [PubMed: 27878313]

67.Rastogi A, Bhansali A. SGLT2 Inhibitors Through the Windows of EMPA-REG and CANVAS Trials: A Review. Diabetes Ther. 2017 Dec;8(6):1245-1251. [PMC free article: PMC5688986] [PubMed: 29076040]

68.Kluger AY, Tecson KM, Barbin CM, Lee AY, Lerma EV, Rosol ZP, Rangaswami J, Lepor NE, Cobble ME, McCullough PA. Cardiorenal Outcomes in the CANVAS, DECLARE-TIMI 58, and EMPA-REG OUTCOME Trials: A Systematic Review. Rev Cardiovasc Med. 2018 Jun 30;19(2):41-49. [PubMed: 31032602]

69.Chaudhry K, Karalliedde J. Chronic kidney disease in type 2 diabetes: The size of the problem, addressing residual renal risk and what we have learned from the CREDENCE trial. Diabetes Obes Metab. 2024 Oct;26 Suppl 5:25-34. [PubMed: 39044385]

70.Perkovic V, Jardine MJ, Neal B, Bompoint S, Heerspink HJL, Charytan DM, Edwards R, Agarwal R, Bakris G, Bull S, Cannon CP, Capuano G, Chu PL, de Zeeuw D, Greene T, Levin A, Pollock C, Wheeler DC, Yavin Y, Zhang H, Zinman B, Meininger G, Brenner BM, Mahaffey KW., CREDENCE Trial Investigators. Canagliflozin and Renal Outcomes in Type 2 Diabetes and Nephropathy. N Engl J Med. 2019 Jun 13;380(24):2295-2306. [PubMed: 30990260]

71.Wang WW, Liu YL, Wang MZ, Li H, Liu BH, Tu Y, Yuan CC, Fang QJ, Chen JX, Wang J, Fu Y, Wan ZY, Wan YG, Wu W. Inhibition of Renal Tubular Epithelial Mesenchymal Transition and Endoplasmic Reticulum Stress-Induced Apoptosis with Shenkang Injection Attenuates Diabetic Tubulopathy. Front Pharmacol. 2021;12:662706. [PMC free article: PMC8367077] [PubMed: 34408650]

72.Zhang W, Zhang Y, Lv W, Kong Z, Wang F, Wang Y. Isoquercitrin improves diabetes nephropathy by inhibiting the sodium-glucose co-transporter-2 pathway. Biochem Biophys Res Commun. 2025 Jan;744:151142. [PubMed: 39708395]

73.Tao Y, Bao J, Zhu F, Pan M, Liu Q, Wang P. Ethnopharmacology of Rubus idaeus Linnaeus: A critical review on ethnobotany, processing methods, phytochemicals, pharmacology and quality control. J Ethnopharmacol. 2023 Feb 10;302(Pt A):115870. [PubMed: 36341819]

74.Valencia-Morales ND, Rodríguez-Cubillo B, Loayza-López RK, Moreno de la Higuera MÁ, Sánchez-Fructuoso AI. Novel Drugs for the Management of Diabetes Kidney Transplant Patients: A Literature Review. Life (Basel). 2023 May 26;13(6) [PMC free article: PMC10304316] [PubMed: 37374048]

75.Augustine T. Simultaneous pancreas and kidney transplantation in diabetes with renal failure: the gold standard? J Ren Care. 2012 Feb;38 Suppl 1:115-24. [PubMed: 22348371]

76.Nagendra L, Fernandez CJ, Pappachan JM. Simultaneous pancreas-kidney transplantation for end-stage renal failure in type 1 diabetes mellitus: Current perspectives. World J Transplant. 2023 Sep 18;13(5):208-220. [PMC free article: PMC10514751] [PubMed: 37746036]

77.Rodriguez Cubillo B, Rodriguez B, Calvo M, de la Manzanara V, Bautista J, Perez-Flores I, Calvo N, Moreno A, Shabaka A, Delgado J, Sanchez-Fructuoso AI. Risk Factors of Recurrence of Diabetic Nephropathy in Renal Transplants. Transplant Proc. 2016 Nov;48(9):2956-2958. [PubMed: 27932117]

78.Hariharan S, Peddi VR, Savin VJ, Johnson CP, First MR, Roza AM, Adams MB. Recurrent and de novo renal diseases after renal transplantation: a report from the renal allograft disease registry. Am J Kidney Dis. 1998 Jun;31(6):928-31. [PubMed: 9631835]

79.Jhee JH, Kee YK, Park JT, Chang TI, Kang EW, Yoo TH, Kang SW, Han SH. A Diet Rich in Vegetables and Fruit and Incident CKD: A Community-Based Prospective Cohort Study. Am J Kidney Dis. 2019 Oct;74(4):491-500. [PubMed: 31040089]

80.Cai Q, Dekker LH, Bakker SJL, de Borst MH, Navis GJ. Dietary Patterns Based on Estimated Glomerular Filtration Rate and Kidney Function Decline in the General Population: The Lifelines Cohort Study. Nutrients. 2020 Apr 16;12(4) [PMC free article: PMC7230954] [PubMed: 32316088]

81.Mahnensmith RL, Zorzanello M, Hsu YH, Williams ME. A quality improvement model for optimizing care of the diabetic end-stage renal disease patient. Semin Dial. 2010 Mar-Apr;23(2):206-13. [PubMed: 20525109]

82.Wang N, Zhang C. Recent Advances in the Management of Diabetic Kidney Disease: Slowing Progression. Int J Mol Sci. 2024 Mar 07;25(6) [PMC free article: PMC10970506] [PubMed: 38542060]

Disclosure: Preeti Rout declares no relevant financial relationships with ineligible companies.

Disclosure: Ishwarlal Jialal declares no relevant financial relationships with ineligible companies.