Diabetic renal disease

Question 1

What is the definition of diabetic nephropathy?

Answer 1

Diabetic nephropathy is defined by the presence of dipstick +ve proteinuria in a person with diabetes. This equates to an albumin concentration of 300mg/L (total protein 0.5g/L). Most patients will also have hypertension and retinopathy, and many will have renal impairment

Question 2

How is a diagnosis of diabetic nephropathy made?

Answer 2

Timed urine collections are too cumbersome for routine clinical care, so spot samples (preferably first morning void specimens) are used, and, in order to allow for urine concentration, the albumin content is corrected for creatinine, giving an albumin:creatinine ratio or ACR. A +ve dipstick test or ACR on two or more occasions over 6 months is usually enough to confirm the diagnosis. Remember to exclude potential confounding causes of a +ve test

Question 3

Give 4 causes of false positives when using ACR.

Answer 3

• Vigorous exercise. • Urinary tract infection. • Presence of blood, e.g. menses. • Concentrated urine (less likely using ACR).

Question 4

What is the major histological change in diabetic nephropathy?

Answer 4

Within 5 years of type 1 diabetes, small, but significant, increases in glomerular capillary basement membrane (GBM) thickness are seen due to an accumulation of matrix material, and recent studies have linked this to hyperfiltration. As nephropathy progresses, GBM width continues to increase, and matrix accumulation occurs in the glomerular mesangium (diffuse glomerulosclerosis). In advanced nephropathy, these accumulations can form large acellular (Kimmelstiel–Wilson) nodules (nodular glomerulosclerosis).

Question 5

What is usually the first sign of diabetic nephropathy?

Answer 5

Albuminuria

Question 6

An albuminuria exceeding 10mg/mmol is indicative of what?

Answer 6

Once albuminuria exceeds an ACR of 10mg/mmol (∼100mg/g), it is usually persistent and represents established nephropathy.

Question 7

What are the 4 keystones of the medical management of diabetic nephropathy?

Answer 7

1. Blood pressure control
2. Glycaemic control
3. CV risk factors
4. Diet

Question 8

What are the key class of antihypertensive medications in diabetic nephropathy?

Answer 8

ACEIs

Question 9

Give the 8 reasons for referral to a renal specialist in the context of diabetes

Answer 9

1. CKD stage 4 or 5 (eGFR <30mL/min/1.73m2).
2. Rapid decline of GFR (eGFR decline >5mL/min/1.73m2/year or >10mL/min/1.73m2/5 years).
3. Microscopic or macroscopic haematuria and/or active urinary sediment.
4. Signs of other systemic disease, such as SLE or systemic sclerosis.
5. Blood pressure outside target despite four or more drugs at optimum titration.
6. Heavy proteinuria (>1g/day or protein:creatinine ratio >100mg/mmol or ACR >70mg/mmol).
7. Family history of genetic causes of kidney disease (e.g. polycystic kidneys).
8. Suspected renal artery stenosis.