Diabetic Nephropathy

Definition

Diabetic nephropathy is a serious complication of diabetes mellitus, characterised by damage to the kidneys' filtering units (glomeruli). This condition can lead to chronic kidney disease (CKD) and, ultimately, end-stage renal disease (ESRD), necessitating dialysis or kidney transplantation.

Aetiology

Diabetic nephropathy is primarily caused by long-term uncontrolled high blood glucose levels and hypertension in individuals with diabetes. These factors contribute to kidney damage over time.

Pathophysiology

Prolonged hyperglycaemia in diabetes leads to the accumulation of advanced glycation end products (AGEs) in the kidneys. These AGEs induce oxidative stress and inflammation, causing thickening of the glomerular basement membrane and expansion of the mesangial matrix. This disrupts the normal filtration process, leading to proteinuria (the presence of excess protein in urine) and progressive kidney damage.

Risk factors

Long-standing diabetes mellitus (type 1 or type 2)
Poor glycaemic control
Hypertension
Smoking
Obesity
Family history of diabetic nephropathy
Race (higher prevalence in African Americans, Hispanics, and Native Americans)

Signs and Symptoms

Proteinuria (early sign)
Hypertension
Oedema (swelling, particularly in the legs and feet)
Fatigue
Foamy urine
Progressive decline in kidney function (e.g., increasing serum creatinine)

Red Flags

Rapidly increasing proteinuria
Sudden worsening of kidney function
Severe hypertension not responsive to treatment
Signs of nephrotic syndrome (e.g., severe oedema, hypoalbuminaemia)

Investigations

Urinalysis to detect proteinuria
Measurement of urine albumin-to-creatinine ratio (ACR) to quantify proteinuria
Blood tests to assess renal function (e.g., serum creatinine, estimated glomerular filtration rate [eGFR])
Blood pressure monitoring
Glycated haemoglobin (HbA1c) to assess long-term glycaemic control
Renal ultrasound to evaluate kidney size and structure
Referral to a nephrologist for further evaluation if there are significant abnormalities

Management

Primary Care Management:

Optimise glycaemic control with lifestyle modifications and medications (e.g., metformin, insulin)
Control blood pressure with ACE inhibitors or angiotensin II receptor blockers (ARBs)
Recommend a low-protein diet to reduce kidney workload
Encourage smoking cessation and weight management
Regular monitoring of kidney function and urine protein levels
Referral to a nephrologist if there is a rapid decline in kidney function or refractory hypertension

Example Management for Diabetic Nephropathy:

A patient with diabetic nephropathy should be managed with tight glycaemic control, targeting an HbA1c of less than 53 mmol/mol. Blood pressure should be maintained below 130/80 mmHg, often requiring an ACE inhibitor or ARB. Regular monitoring of renal function and urine protein levels is essential. Lifestyle modifications, including smoking cessation, weight management, and dietary changes, should be strongly encouraged. If the patient's kidney function declines rapidly or hypertension is not well controlled, referral to a nephrologist is indicated.

References:

NICE. (2023). Chronic Kidney Disease in Adults: Assessment and Management. Retrieved from https://www.nice.org.uk/guidance/ng203
NHS. (2023). Diabetic Kidney Disease. Retrieved from https://www.nhs.uk/conditions/diabetic-kidney-disease/
American Diabetes Association. (2023). Standards of Medical Care in Diabetes. Retrieved from https://diabetesjournals.org/care/article/46/Supplement_1/S1/69817/Standards-of-Medical-Care-in-Diabetes-2023-Abridged
Ruggenenti, P., & Remuzzi, G. (2016). Nephropathy of type 1 and type 2 diabetes: diverse pathophysiology and same treatment? Nephrology Dialysis Transplantation, 21(6), 2061-2066.
O'Sullivan, S. B., & Schmitz, T. J. (2016). Physical Rehabilitation. 6th ed. F.A. Davis Company.
Ropper, A. H., & Samuels, M. A. (2019). Adams and Victor's Principles of Neurology. 11th ed. McGraw-Hill Education.