Epidemiology

• Kidney damage in type 1 diabetes is the largest cause of renal failure in the working age group.^[1]
• Kidney disease in people with type 2 diabetes is increasing because of the increasing prevalence of people with diabetes, improved cardiovascular survival and the trend to younger onset of type 2 diabetes.^[2]
• The prevalence of microalbuminuria in patients with type 1 diabetes at 30 years' disease duration is approximately 40%.^[3]
• The prevalence of microalbuminuria in patients with type 2 diabetes at 10 years' disease duration is approximately 20-25%.^[3]

Definitions

• Microalbuminuria: albumin:creatinine ratio (ACR) greater than or equal to 2.5 mg/mmol (men) or 3.5 mg/mmol (women), or albumin concentration greater than or equal to 20 mg/l.
• Proteinuria: albumin:creatinine ratio greater than or equal to 30 mg/mmol or albumin concentration greater than or equal to 200 mg/l.

Detection and surveillance of kidney problems

Clinical features are usually absent until advanced chronic kidney disease develops. However, there may be features of poor diabetes control (eg thirst, lethargy) and it is essential to assess for other possible complications of diabetes.

• Arrange recall and annual review for all people with type 1 and type 2 diabetes.
• Measure urinary albumin:creatinine ratio or albumin concentration annually. Use a first morning urine sample when possible.
• Repeat the test if an abnormal albumin:creatinine ratio is obtained (in the absence of proteinuria or a urinary tract infection) at each of the next two clinic visits but within a maximum of 3-4 months.^[2]
• Measure serum creatinine and estimated glomerular filtration rate (eGFR) annually.

Other initial investigations to assess cause of proteinuria include urinalysis, urine culture and microscopy, and renal ultrasound. Renal biopsy may occasionally be required.^[3] Other investigations for monitoring of diabetes include glycosylated haemoglobin (HbA1c) and serum lipids.

Differential diagnosis

• Raised albumin excretion rate in type 2 diabetes is often a sign of general vascular damage rather than specific renal damage. It is a useful arterial risk marker.
• Abnormal serum creatinine in type 2 diabetes is often due to renal arterial disease and/or diuretic therapy for cardiac failure rather than to diabetic nephropathy.
• Detection and surveillance of specific kidney problems therefore depends on identifying progression of albumin excretion rate and serum creatinine, in the absence of other causes.
• Consider a non diabetes-related cause of renal disease (full history and examination, urinalysis, renal ultrasound, and other investigations as appropriate). Other renal disease should be suspected:^[1][2]
  • In the absence of progressive retinopathy
  • If blood pressure is particularly high or resistant to treatment
  • If proteinuria develops suddenly
  • If they had a documented normal ACR and develop heavy proteinuria (ACR >100 mg/mmol)
  • If significant haematuria is present
  • In the presence of systemic ill health

Management

Primary prevention

• Optimal control of blood glucose and blood pressure.
  • The Diabetes Control and Complications Trial (DCCT) found that a reduction in mean HbA1c from 9.0% to 7.3% in people with type 1 diabetes was associated with a 39% reduction in microalbuminuria and 54% reduction in proteinuria over 6.5 years. However, no clear benefit was seen in the treatment of established microalbuminuria in people with type 1 diabetes.^[4]
  • The United Kingdom Prospective Diabetes Study (UKPDS) also showed that a reduction in blood pressure from 154/87 to 144/82 mm Hg was associated with an absolute risk reduction of developing microalbuminuria of 8% over 6 years in patients with type 2 diabetes.^[5]
• For type 2 diabetes, this also means early diagnosis and therefore management before complications have already started.
• Smoking cessation.

Microalbuminuria and proteinuria^[1][6]

• Ensure good blood glucose control (HbA1c below 6.5-7.5%, according to the individual's target).
• Measure, assess and manage cardiovascular risk factors aggressively (smoking, glucose, raised lipids, high blood pressure).
• Angiotensin-converting enzyme (ACE) inhibitors should be started and titrated to full dose in all adults with confirmed nephropathy (including those with microalbuminuria alone) and type 1 diabetes.
• If ACE inhibitors are not tolerated, angiotensin ll receptor antagonists should be substituted but combination therapy with both ACE inhibitors and angiotensin ll receptor antagonists is not recommended at present.
• ACE inhibitor therapy (and angiotensin II receptor antagonists) should be used with caution in those with:
  • Peripheral vascular disease or known renovascular disease
  • Raised serum creatinine
• Blood pressure should be maintained below 130/80 mm Hg by addition of other antihypertensive drugs if necessary.
• Adults with type 1 diabetes and nephropathy should be advised about the advantages of not following a high-protein diet. However, dietary protein restrictions are not recommended.^[3]
• Referral criteria for tertiary care should be agreed between local diabetes specialists and nephrologists. Patients with an eGFR below 30 ml/min/1.73 m² should be referred to a specialist.^[7]
• Measure urine albumin and serum creatinine levels more frequently (eg six-monthly for microalbuminuria but normal serum creatinine). The frequency will depend on the individual situation of the patient.
• For management of chronic renal failure see separate article Chronic Kidney Disease.

Prognosis

Type 1

• Approximately 19% to 24% of patients with microalbuminuria develop diabetic nephropathy. Systolic blood pressure, glycated haemoglobin and triglycerides are significantly higher in people with type 1 diabetes who progress to diabetic nephropathy than for those who do not.^[1]
• Five-year follow-up of microalbuminuric patients with type 1 diabetes showed that 19% progressed to diabetic nephropathy and 33% regressed to normoalbuminuria.
• With aggressive antihypertensive therapy, proteinuric type 1 patients lose glomerular filtration rate (GFR) at approximately 4 ml/min/year.^[3]
• When proteinuria and hypertension are present, the standardised mortality ratio is increased 11-fold in men and 18-fold in women.^[3]

Type 2

• 20% of microalbuminuric type 2 patients who survive for 10 years develop proteinuria.^[3]
• Treated proteinuric, hypertensive type 2 patients lose glomerular function at a rate of approximately 8 ml/min/year.
• Patients with microalbuminuria have a twofold to fourfold increase in cardiovascular morbidity and mortality.
• The 4-year mortality is 32% for microalbuminuric type 2 patients and 50% for proteinuric type 2 patients.
• When proteinuria and hypertension are present, the standardised mortality ratio is increased fivefold in men and eightfold in women with type 2 diabetes.^[3]