Diabetic Kidney Disease

Diabetic Kidney Disease (DKD) is a chronic microvascular complication of diabetes mellitus characterized by persistent albuminuria, progressive decline in estimated glomerular filtration rate (eGFR), or both, in the absence of other primary kidney diseases. It is the leading cause of chronic kidney disease (CKD) and end-stage kidney disease (ESKD) worldwide.

Diabetic nephropathy is a specific form of diabetic kidney disease characterized by persistent microalbuminuria (30–300 mg/g), diabetic retinopathy, and progressive deterioration of kidney function. Early detection through routine screening, optimization of glycaemic control, blood pressure management, and timely initiation of renoprotective therapy are essential to delay disease progression and reduce cardiovascular morbidity and mortality.

Epidemiology

Diabetic Kidney Disease develops in approximately 20–40% of individuals with diabetes mellitus and is the leading cause of end-stage kidney disease globally. The risk is influenced by the duration of diabetes, glycaemic control, hypertension, obesity, smoking, and genetic susceptibility. In Tanzania and other low- and middle-income countries, the increasing prevalence of type 2 diabetes has contributed substantially to the growing burden of diabetic kidney disease, often with delayed diagnosis due to limited routine screening.

Risk factors

Common risk factors include:

• Type 1 diabetes mellitus

• Type 2 diabetes mellitus

• Long duration of diabetes

• Poor glycaemic control

• Hypertension

• Persistent albuminuria

• Obesity

• Dyslipidaemia

• Smoking

• Family history of kidney disease

• Cardiovascular disease

• Older age

• Diabetic retinopathy

• Previous episodes of acute kidney injury

Pathophysiology

Diabetic Kidney Disease develops as a consequence of chronic hyperglycaemia, which causes structural and functional changes within the glomeruli. Persistent hyperglycaemia leads to glomerular hyperfiltration, thickening of the glomerular basement membrane, mesangial expansion, podocyte injury, and progressive glomerulosclerosis.

These changes increase urinary albumin excretion and gradually reduce glomerular filtration rate. Persistent activation of inflammatory and fibrotic pathways contributes to irreversible nephron loss. Progressive kidney dysfunction is associated with increased cardiovascular risk and may ultimately progress to end-stage kidney disease requiring dialysis or kidney transplantation.

Clinical presentation

Early Diabetic Kidney Disease is usually asymptomatic and detected through routine screening.

Patients with progressive disease may present with:

• Persistent albuminuria

• Progressive decline in kidney function

• Lower limb oedema

• Facial puffiness

• Fatigue

• Generalized weakness

• Reduced urine output in advanced disease

• Poor appetite

• Nausea and vomiting

• Symptoms of uncontrolled diabetes

• Symptoms of chronic kidney disease

Clinical signs may include:

• Hypertension

• Peripheral oedema

• Features of diabetic retinopathy

• Pallor secondary to anaemia

• Signs of fluid overload in advanced disease

Diagnostic criteria

Diabetic Kidney Disease is diagnosed in patients with diabetes mellitus who have one or more of the following persisting for at least three months:

• Persistent albuminuria.

• Reduced estimated glomerular filtration rate (eGFR).

• Both albuminuria and reduced eGFR.

Diabetic nephropathy is suggested by:

• Microalbuminuria (30–300 mg/g).

• Presence of diabetic retinopathy.

• Progressive decline in kidney function.

Alternative causes of kidney disease should be considered when atypical clinical features are present.

Investigations

Recommended investigations include:

Urine investigations

• Urinalysis (dipstick and urine microscopy).

• Urine albumin-creatinine ratio (ACR).

• Urine protein-creatinine ratio where indicated.

Assessment of kidney function

• Serum creatinine.

• Estimated glomerular filtration rate (eGFR).

• Blood urea nitrogen (BUN).

Imaging

• Kidney-Ureter-Bladder (KUB) ultrasound.

Kidney biopsy

Kidney biopsy should be considered when the diagnosis is uncertain or when another kidney disease is suspected, including:

• Albuminuria greater than 300 mg/g occurring within five years of onset of type 1 diabetes mellitus.

• Presence of red blood cell casts.

• Dysmorphic red blood cells.

• White blood cell casts.

• Presence of another systemic disease such as systemic lupus erythematosus.

• Rapid decline in eGFR greater than 5 mL/min/1.73 m² per year.

Additional investigations

• Glycated haemoglobin (HbA1c).

• Serum electrolytes.

• Lipid profile.

• Fundoscopic examination for diabetic retinopathy.

• Full blood count.

Management

Management aims to:

• Slow progression of kidney disease.

• Optimize glycaemic control.

• Control blood pressure.

• Reduce albuminuria.

• Prevent cardiovascular complications.

• Delay progression to end-stage kidney disease.

Non-pharmacological treatment

General measures include:

• Optimize glycaemic control according to the Diabetes Mellitus guideline.

• Restrict dietary sodium intake.

• Encourage a balanced diet with appropriate protein intake.

• Maintain healthy body weight.

• Encourage regular physical activity.

• Stop smoking.

• Optimize blood pressure control.

• Treat dyslipidaemia.

• Avoid nephrotoxic medications.

• Monitor kidney function and albuminuria regularly.

• Screen for diabetic retinopathy and other diabetic complications.

Pharmacological treatment

Treatment should be individualized according to kidney function (eGFR).

For patients with CKD Stages 1–2 (eGFR ≥60 mL/min/1.73 m²):

• Manage diabetes according to the Diabetes Mellitus guideline.

• For adults with type 2 diabetes mellitus and high cardiovascular risk, consider:

  • Empagliflozin 10 mg orally once daily.

  • OR

  • Sitagliptin 50 mg orally once daily.

Strong consideration should be given to the use of sodium-glucose cotransporter-2 (SGLT2) inhibitors where appropriate.

For patients with CKD Stage 3 (eGFR 30–59 mL/min/1.73 m²):

• Gliclazide 40–80 mg orally every 12 hours.

• OR

• Glimepiride 1–8 mg orally once daily.

Empagliflozin 10 mg orally once daily may be continued or initiated where indicated and clinically appropriate.

Metformin and long-acting sulfonylureas should be used cautiously, with dose adjustment according to kidney function.

For patients with CKD Stage 4 (eGFR 15–29 mL/min/1.73 m²):

• Gliclazide 40–80 mg orally every 12 hours.

• OR

• Glimepiride 1–8 mg orally once daily.

Where appropriate:

• Sitagliptin 25 mg orally once daily.

Patients receiving insulin usually require dose reduction because of reduced insulin clearance.

For patients with CKD Stage 5 (eGFR <15 mL/min/1.73 m²) or those receiving dialysis:

• Insulin is the preferred treatment.

• Insulin doses should be reduced as kidney function declines.

• Pioglitazone 15–30 mg orally once daily may be considered in selected patients without contraindications such as heart failure or significant fluid retention.

Patients with albuminuria should receive an ACE inhibitor or angiotensin receptor blocker according to CKD and hypertension treatment guidelines unless contraindicated.

Referral

Refer patients to a physician or nephrologist when:

• Rapid decline in kidney function.

• Persistent macroalbuminuria.

• eGFR below 60 mL/min/1.73 m².

• Resistant hypertension.

• Uncertain diagnosis requiring kidney biopsy.

• Advanced CKD (Stages 4 or 5).

• Preparation for kidney replacement therapy.

• Suspected non-diabetic kidney disease.

Complications

Potential complications include:

• Progressive chronic kidney disease.

• End-stage kidney disease.

• Persistent proteinuria.

• Hypertension.

• Cardiovascular disease.

• Acute kidney injury.

• Hyperkalaemia.

• Anaemia.

• Mineral and bone disorders.

• Fluid overload.

• Increased risk of dialysis.

• Premature death.

Prognosis

The prognosis depends on the duration of diabetes, glycaemic control, blood pressure control, degree of albuminuria, and stage of kidney disease at diagnosis. Early identification combined with intensive management of blood glucose, hypertension, and cardiovascular risk factors can substantially delay progression to end-stage kidney disease and reduce cardiovascular events. Advanced disease is associated with increased morbidity, mortality, and healthcare utilization.

Prevention

Preventive measures include:

• Optimal glycaemic control.

• Effective blood pressure control.

• Annual screening for albuminuria and eGFR in patients with diabetes.

• Early initiation of ACE inhibitors or angiotensin receptor blockers in patients with albuminuria where indicated.

• Appropriate use of SGLT2 inhibitors in eligible patients.

• Smoking cessation.

• Management of dyslipidaemia.

• Maintenance of healthy body weight.

• Regular physical activity.

• Avoidance of nephrotoxic medications.

• Early treatment of cardiovascular risk factors.