14th July 2024

Diabetic nephropathy

Background

Diabetes is the commonest cause of chronic kidney disease (CKD) and end stage renal failure (ESRF) in the world with diabetic nephropathy increasing both morbidity and mortality in diabetic patients. Peak incidence of nephropathy is between 10 and 20 years after diagnosis and patients with type 1 diabetes are more likely to follow a predictable decline toward ESRF than type 2 diabetes; perhaps due to higher mortality associated with cardiovascular events in type 2 patients.

Multiple mechanisms are involved in the development of diabetic nephropathy. These include persistent hyperglycaemia, increased oxidative stress and initial hyperfiltration leading to micro-endovascular damage and glomerular sclerosis.  The development of secondary hypertension further worsens the picture.

Diagnosis and classification

As a common complication of diabetes, patients should be screened for renal disease at least once a year. A renal blood panel should be measured with an eGFR of <60ml/min/1.73m2 or a creatinine increase of >20% when compared with previous prompting further investigation. A measurement of proteinuria using a first pass spot urinary albumin:creatinine ratio (ACR) should be undertaken in all patients – a measurement of >3 mg/mmol on two or more occasions should be regarded as clinically important proteinuria.  As in those without diabetes, renal ultrasound may be indicated in cases of accelerated progression of disease and/or red flag features, e.g. persistent haematuria.

A five point staging system is used to classify the severity of diabetic nephropathy (see table below).

Patients are classically asymptomatic in the earlier stages of nephropathy.  Peripheral oedema, difficult to control hypertension and constitutional symptoms such as fatigue, itch and nausea becoming particularly prevalent from stage III to IV onwards.

Management

A persistent reduction in eGFR (<60 for 90 days or more) or elevation in ACR (>3 for 90 days or more) should prompt pharmacological management. An angiotensin converting enzyme inhibitor (ACEI) or an angiotensin receptor blocker (ARB) should be offered to those with an ACR of >3 mg/mmol and titrated to the highest dose tolerated. All anti-hypertensives have a role but ACEIs and ARBs are most effective in reducing intraglomerular pressure and albuminuria.

Hyperglycaemia and hypertension should be addressed as per NICE targets and those with stage III disease or more should be offered atorvastatin 20mg.  Patients should be advised to stop smoking and encouraged to lose excess body weight.

References

• National Institute for Health and Care Excellence. Chronic kidney disease: assessment and management. London: NICE; 2021. (NICE Guideline No. 203.)  Available from: https://www.nice.org.uk/guidance/ng203
• Barratt J, Topham P, Carr S, Arici M. Oxford Desk Reference Nephrology 2ⁿᵈ ed. Oxford: Oxford University Press; 2021 Jul
• Kidney international supplements. KDIGO 2012 Clinical practice guideline for the evaluation and management of chronic kidney disease. Kidney international supplements; 2013. Available from: https://kdigo.org/wp-content/uploads/2017/02/KDIGO_2012_CKD_GL.pdf
• National Institute for Health and Care Excellence. Type 2 Diabetes in Adults: management. London: NICE; 2022. (NICE Guideline No. 28) Available from: https://www.nice.org.uk/guidance/ng28/chapter/Recommendations#reviewing-drug-treatments