Introduction:

Diabetic kidney disease (DKD) is a prevalent complication of diabetes mellitus and a leading cause of end-stage renal disease. Identifying the risk factors associated with DKD, understanding its clinical features, and implementing appropriate management strategies are crucial for healthcare professionals to mitigate its impact on patient outcomes. This article aims to provide a comprehensive overview of the risk factors, clinical features, and management options for DKD, emphasizing recent research findings.

Risk factors for diabetic kidney disease:

• Hyperglycemia: The duration and severity of hyperglycemia are the most significant risk factors for DKD (1, 2).
• Hypertensionis a significant risk factor for DKD, as it can damage the small blood vessels in the kidneys (3, 4).
• Dyslipidemia,particularly elevated triglycerides and low HDL cholesterol levels, is a well-established risk factor for DKD (5). Poor lipid control is associated with increased albuminuria, which is a significant marker for DKD progression (6).
• Smokingis an additional risk factor for DKD, as it can exacerbate kidney damage caused by diabetes. Smoking is believed to cause endothelial dysfunction and oxidative stress that can lead to damage to renal function (7).
• Obesityis another significant risk factor for DKD. Recent evidence suggests that bariatric surgery may lead to substantial BMI reduction and better glycemic control in diabetic patients, potentially reducing the risk of DKD (8).
• Ethnicity and Genetic Predisposition: Certain ethnicities, including African American, Hispanic, and Native American populations, have a higher risk of developing DKD. Genetic predisposition may also play a role in DKD development and progression (9).

Clinical features of diabetic kidney disease:

• Microalbuminuria and proteinuria: the earliest clinical manifestation of DKD is the presence of microalbuminuria, defined as a urinary albumin excretion rate of 30-300 mg/24 hours or an albumin-to-creatinine ratio (ACR) of 30-300 mg/g. Microalbuminuria progresses to overt proteinuria (ACR >300 mg/g or urine protein excretion >500 mg/24 hours) as DKD advances (1, 5).
• Hypertensionis a common comorbidity in patients with DKD and often precedes the development of renal dysfunction (10).
• Declining Renal Function: As DKD progresses, there is a gradual decline in renal function. This decline is characterized by a decrease in the glomerular filtration rate (GFR), indicated by an elevated serum creatinine level and a decrease in estimated GFR (eGFR). The decline in eGFR is associated with an increased risk of end-stage renal disease (11).
• Hypoalbuminemia and edema: as DKD progresses, protein is lost through the kidneys, resulting in hypoalbuminemia (serum albumin <3.5 g/dL). Hypoalbuminemia contributes to the development of edema, particularly in the lower extremities and periorbital region (12).
• Anemia: anemia is a common complication of DKD and is often multifactorial. Reduced erythropoietin production, shortened red blood cell survival, inflammation, and iron deficiency contribute to the development of anemia in DKD (13).

Management strategies for diabetic kidney disease:

• Glycemic Control: intensive glucose-lowering regimens, including lifestyle modifications and pharmacological interventions such as metformin, sodium-glucose cotransporter-2 inhibitors (SGLT2 inhibitors), and glucagon-like peptide-1 receptor agonists (GLP-1 RAs), have shown benefits in reducing the risk of DKD progression. Regular monitoring of glycated hemoglobin (HbA1c) levels and adjustment of therapy are essential to achieving target goals (1, 14, 15).
• Blood Pressure Control: strict blood pressure control, particularly with angiotensin-converting enzyme inhibitors (ACEIs) or angiotensin receptor blockers (ARBs), is crucial in DKD management. Target blood pressure goals may vary depending on the severity of renal impairment, but generally aim for systolic blood pressure <140 mmHg and diastolic blood pressure <90 mmHg (5). Individualized treatment plans, including lifestyle modifications and tailored antihypertensive medications, should be implemented to achieve optimal control.
• Lipid Management: Statins are the first-line agents for managing dyslipidemia in patients with DKD, targeting LDL cholesterol levels with a goal of <70 mg/dL, or a 50% reduction from baseline (14). In patients with persistent triglyceride elevation despite optimal glycemic control, fibrates may be considered. Regular monitoring of lipid profiles is necessary to assess treatment response.
• Smoking cessationcan reduce the risk of cardiovascular complications. Therefore, healthcare professionals should provide smoking cessation counseling and support to all patients with DKD. (7)
• Renal Replacement Therapy: in patients with advanced DKD and end-stage renal disease (ESRD), renal replacement therapy is necessary. Options include hemodialysis, peritoneal dialysis, or kidney transplantation. Early consultation with nephrologists and transplant centers is crucial to optimizing patient outcomes. Attention to fluid and electrolyte balance, anemia management, and nutritional support are essential components of DKD management in patients receiving renal replacement therapy. (10)
• Lifestyle modifications: Encouraging patients to adopt a healthy lifestyle, including regular physical activity, weight management, and a balanced diet, has shown potential benefits in preventing DKD progression and improving overall health (15).

References:

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2. Araki S, Haneda M, Sugimoto T, et al. Factors associated with frequent remission of microalbuminuria in patients with type 2 diabetes. J Diabetes Investig. 2011; 2(5): 384-389.

3. Ruggenenti P, Fassi A, Ilieva AP, et al. Preventing microalbuminuria in type 2 diabetes. N Engl J Med. 2004; 351(19): 1941-1951.

4. Ferrannini E, Cushman WC. Diabetes and hypertension: the bad companions. Lancet. 2012;380(9841):601-610.

5. de Boer IH, Bangalore S, Benetos A, et al. Diabetes and hypertension: a position statement by the American Diabetes Association. Diabetes Care. 2017; 40(9):1273-1284.

6. Gooding KM, Ding HQ, De Boer IH, et al. Dyslipidemia and Risk of Cardiovascular Disease in CKD: Results From the CRIC (Chronic Renal Insufficiency Cohort) Study. J Am Heart Assoc. 2020; 9(14):e016649.

7. Yacoub R, Habib H, Lahdo A, et al. Association between cigarette smoking and albuminuria in diabetic patients. Nephron Clin Pract 2012;122:67–72.

8. Arterburn DE, Olsen MK, Smith VA, et al. Association between bariatric surgery and long-term survival. JAMA. 2015; 313(1):62-70.

9. Maric-Bilkan C, Flynn ER, Chade AR. Renal disease in diabetic ethnic minorities. J Am Soc Nephrol. 2019; 30(7): 1272-1281.

10. Molitch ME, Adler AI, Flyvbjerg A, et al. Diabetic kidney disease: summary of Kidney Disease: Improving Global Outcomes 2012 Clinical Practice Guideline. Diabet Med. 2014; 31(3): 257-267.

11. Perkins BA, Ficociello LH, Silva KH, et al. Regression of Microalbuminuria in Type 1 Diabetes. N Engl J Med. 2003; 348(23): 2285-2293.

12. Tonneijck L, Muskiet MHA, Smits MM, et al. Glomerular Hyperfiltration in Diabetes: Mechanisms, Clinical Significance, and Treatment. J Am Soc Nephrol. 2017; 28(4): 1023-1039.

13. Thomas MC. Anemia in diabetes: marker or mediator of microvascular disease? Nature reviews. Nephrology. 2017; 13(9): 567–578.

14. Arca M, Pigna G. Treating hypercholesterolemia and preventing cardiovascular diseases: focus on ezetimibe and other novel lipid-lowering strategies. Int J Cardiol. 2018;253:236-245.

15. Pistea C, Varga A, Zapciu A, et al. Nonpharmacological Management of Diabetic Kidney Disease. Medicina (Kaunas). 2020; 56(8): 412.