Renal disease and diabetes
Renal impairment is important in patients with chronic diseases or on multiple drug therapy and serum creatinine should be checked annually. Diabetic nephropathy is an important long-term complication of diabetes, which is characterised by persistent proteinuria, hypertension and a progressive decline in renal function. The absence of retinopathy or the presence of haematuria should prompt investigation for other possible forms of renal disease. A definitive diagnosis of diabetic nephropathy can be made by renal biopsy, although this is unnecessary in most cases.
Persistent proteinuria confers an eighty to one hundred fold increased mortality due largely to cardiovascular disease and such patients often succumb before the need for renal support arises. Survivors with persistent proteinuria eventually progress to end stage renal failure requiring dialysis or transplantation.
Microalbuminuria is an early marker of diabetic renal disease and predicts the onset of overt nephropathy in both Type 1 and Type 2 diabetes. Microalbuminuria is also a significant independent risk factor for the development and progression of cardiovascular disease.
Aggressive management of blood pressure can retard the progression of diabetic renal disease at all stages.
It should then be split into the following sections:
Screening for diabetic renal disease
Definitions
Assessment of dipstick positive patients
Assessment of dipstick negative patients
Management of Diabetic Renal Disease
Referral for specialist renal advice
Screening for diabetic renal disease
Who People with diabetes aged 12 years or over
When At diagnosis and annually
How Dipstick for proteinuria (Albustix or equivalent)
Microalbumin estimation if dipstick negative
Outcome
 Dipstick positive – see 19.2.1 – Assessment of dipstick positive patients
 Dipstick negative
– see 19.2.2 – Assessment of dipstick negative patients

Definitions
Spot urine samples (for screening)
Albustix
Albumin/creatinine ratio (ACR)
Dipstick one plus or greater (>200mg/l) indicates proteinuria
The ratio of urinary albumin to creatinine concentration. This is a screening test for microalbuminuria.
Normal values – female <3.5mg/mmol, male
<2.5mg/mmol
Timed overnight urine collections (for diagnosis)* – see Appendix 10
Normoalbuminuria Normal albumin excretion rate <20 µg/min
Microalbuminuria
Proteinuria
Albumin excretion rate 20200µg/min
Albumin excretion rate > 200µg/min
Spot protein/creatinine ratio (PCR) > 70mg/mmol
24hr urinary protein > 500mg
Assessment of dipstick positive patients

Consider urinary infection or other non diabetic causes

Repeat test

Persistent proteinuria, when confirmed on two consecutive occasions, should be quantified using a protein/ creatinine ratio measurement on a spot sample.

Review result of recent serum creatinine and blood pressure
 Persistent “dipstick positive” proteinuria negates the need for measurement of microalbuminuria
Assessment of dipstick negative patients

Screen for microalbuminuria

First voided urine sample after sleep, for albumin/creatinine ratio (ACR)
 Reject samples with evidence of infection.
 Normal (male < 2.5, female < 3.5 mg/mmol) repeat in twelve months.
 Abnormal – Re-test.

If repeat test abnormal proceed to timed overnight urine collection*
 AER <20ug/min – revert to annual screening
 AER >20ug/min – microalbuminuria confirmed
* ACR levels persistently in excess of 10 mg/mmol always indicate an AER >
20
 g/min, and in such circumstances a timed collection may be omitted.

In some clinics preliminary screening is performed to identify normal results using the
Klinitek 50.
 Result from Klinitek 50 – both ACR <3.5 and urinary albumin concentration <10 mg/l = normal albuminuria. Repeat in 12 months.
 Result from Klinitek 50 –ACR >3.5 and/or urinary albumin concentration >10 mg/l
= send first voided urine to Lab for further analysis.
Management of Diabetic Renal Disease

Patients with diabetic renal disease require frequent and intensive monitoring.

Microalbuminuria and proteinuria confirm diabetic renal disease and aggressive management of blood pressure and other risk factors is essential to preserve renal function.

These patients are also at high risk of retinopathy, autonomic neuropathy and cardiovascular disease.

All patients with microalbuminuria or proteinuria should be commenced on ACE inhibitor therapy. The dosage should be gradually increased to the maximum tolerated dose. Those intolerant of ACE inhibitors should be given Angiotensin II antagonists. Annual measurements of creatinine and albumin/creatinine ratio
(protein/creatinine ratio if proteinuric) should be continued.

Lowering blood pressure in relatively hypertensive microalbuminuric patients reduces albumin excretion and progression to nephropathy. All agents which lower blood pressure reduce albumin excretion, although ACE inhibitors and AIIAs probably have a class specific effect independent of their hypotensive effect and are the drugs of choice for initial therapy.

Blood pressure should be maintained <140/80 mm Hg in all patients (SIGN 55). In
Type 1 patients with microalbuminuria or proteinuria the target blood pressure should be lower. The Aberdeen Renal Clinic currently recommend <125/75 .

Insulin or sulphonylurea requirements usually decrease with advancing renal impairment. Metformin should be discontinued when serum creatinine is > 150
 mol/l.

Patients with Type 1 diabetes and proteinuria may benefit from advice from a
Dietitian. A reduction of protein intake to 0.6-0.8 g/kg per day may reduce progression of overt diabetic nephropathy.

Patients with diabetic renal disease have a high risk of cardiovascular co-morbidity and should be managed aggressively.
See Appendix 8 - Algorithm for microalbuminuria screening

Referral for specialist renal advice

Consider referral to specialist renal services when creatinine >150
 mol/l (male),
>130
 mol/l (female) or protein/creatinine ratio >300 mg/µmol.

Referral should also be considered for features suggestive of nephrotic syndrome or if persistent proteinuria is not thought to be explained by diabetes (considering the duration of diabetes and absence of other microvascular complications).

The presence of both blood and protein may also be indicative of an alternative renal pathology and in cases where this is persistent i.e. detected on more than 2 occasions a referral should be considered. Isolated haematuria will require separate evaluation and is not a feature of diabetic nephropathy.

Specialist renal assessment will include assessment for non-diabetic renal conditions if necessary, assessment of GFR and estimation of likely progression of renal disease. Patients with stable renal disease will be discharged back to routine diabetes care (primary or secondary care) with advice on a threshold for further referral.