Tayside Diabetes MCN Handbook
Screening and Management of Kidney Complications

Diabetic nephropathy is detected clinically by the presence of microalbuminuria or proteinuria
The time course to nephropathy is usually 15-25 years following the onset of diabetes
The course may appear shorter in Type 2 patients, because diabetes may have been present but undiagnosed for several years
Development of renal disease is facilitated by poor glycaemic control, hypertension, dyslipidaemia and smoking
Early detection and effective treatment can slow progression of nephropathy, therefore screening is vital
The possibility of non-diabetic renal disease should be considered if atypical features, such as haematuria are present, or if retinopathy is absent.

What is Microalbuminuria?

Microalbuminuria refers to urine albumin concentrations that are below the limit of detection of routine urine dipsticks (i.e. dipstick negative proteinuria).
In Type 1 diabetic patients, microalbuminuria (which initially is intermittent), is a marker of early nephropathy
In Type 2 diabetic patients, microalbuminuria correlates with macrovascular disease and underlying hypertension and is a marker for nephropathy.
Microalbuminuria in Type 2 diabetes should be viewed as an additional cardiovascular risk factor. Co-existing CHD risk factors should be treated aggressively in Type 2 diabetic patients who are microalbumin positive.
In both types of diabetes, aggressive anti-hypertensive therapy, improved glycaemic control, and management of dyslipidemia may retard the progression of nephropathy

What is Proteinuria?

Proteinuria refers to urine albumin concentrations that are detectable by routine dipsticks (i.e. dipstick positive). However dipstick testing of urine is no longer recommended for the diagnosis and monitoring of proteinuria.
Urinary albumin creatinine ratio (ACR) is the preferred measurement for diagnosing and monitoring diabetic nephropathy.
It is not possible to report an albumin creatinine ratio if the concentration of albumin in the sample exceeds the maximum value that can be measured (approximately 1850mg/L). In this case, the protein creatinine ratio (mg/mmol creatinine) is automatically done and reported by the lab and an appropriate comment is issued.
For non-diabetic individuals, the urinary protein creatinine ratio (PCR) is the first line investigation for proteinuria.

Screening for Diabetic Nephropathy

Screen all patients aged 12 and over
Test at diagnosis and at regular intervals, usually annually
Perform a dipstick test at the point of care
Send a random urine sample to the biochemistry lab for urine albumin creatinine ratio (ACR)
Check U&Es (eGFR).

Urine testing - what samples are needed?

Since January 2010, the lab have reported albumin creatinine ratios (ACR) on all requests for urinary micro-albumin measurement. This decision was taken in the context of national and international guidance relating to the diagnosis and monitoring of chronic kidney disease (CKD) and diabetes. See SIGN and NICE Guidance.
A random urine sample can be sent to check for the albumin creatinine ratio (ACR). This is a change to diabetes screening practice, which previously required an early morning specimen, but it is more convenient for many patients.
In some cases, an early morning sample may still be needed to confirm proteinuria. If this is the case, there will be an appropriate comment on the lab report to reflect this.
If the urine creatinine concentration is less than 1.0mmol/L the lab report will carry a comment indicating that the urine is dilute and should be repeated.

What other tests should be done?

The laboratory no longer automatically performs a dip stick test on urine samples that have been submitted for testing. However, it is good practice to dip stick test urine at the point of care to check for the presence of blood and other abnormalities, such as if a urinary tract infection is suspected.
A negative dip stick test for leukocyte esterase (white cells) is a useful test to rule out UTI when combined with a negative nitrite test (negative predictive value of 95%).
If blood is present, consider the need for other investigations, such as USS and Cytoscopy in line with Urology guidlines.
If both blood and protein are present, consider checking CRP, ANA, ANCA and protein electrophoresis to look for other causes such as vasculitis or myeloma.

Interpreting the results

Interpretation of results
Patient Group	Sex	Albumin/Creatinine Ratio (mg/mmol)	Protein/Creatinine Ratio (mg/mmol)
Diabetic	Male	<2.5*
	Female	<3.5*
Non-Diabetic	Both	<30	<50
		If ACR = 30 to 69mg/mmol, confirm result on EMU	If PCR = 50 to 99mg/mmol, confirm result on EMU
*If ACR > 70mg/mmol creatinine or PCR > 100mg/mmol cratinine, consider referral to the combined Diabetic Renal Clinic

EMU = early morning urin specimen

ACR = Albumin Creatinine Ratio

PCR = Protein Creatinine Ratio

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Estimated Glomerular Filtration Rate (eGFR)

What is eGFR?

eGFR is estimated Glomerular Filtration Rate, which is calculated from the serum creatinine concentration, age and sex. The most widely used method for this is termed "the abbreviated MDRD equation" and this has proved to be both robust and accurate. GFR in health individuals is approximately 100mL/min/1.73m2.

What are the caveats?

It is vital to remember that eGFR provides an estimate only. A 20% fall in eGFR is almost certain to reflect an important change. Larger differences from the true GFR are possible, for example, eGFR is not likely to be accurate in people at extremes of body type, for example, if patient is malnourished or if there is an amputation.
Race: Some racial minorities may not fit the MDRD equation well as the calculation was originally derived from US white and black patients. Since race is not included in the equation used in NHS Tayside, the reported result should be increased by around 20% for a black patient. In the UK white population, and probably in Asians living in the UK, the equation seems to work well. It may not perform adequately in all groups.
Stability of serum creatinine concentration; eGFR calculations assume that the concentration of creatinine in the serum is stable over days or longer. Estimates are not valid if it is changing rapidly.
Age: The MDRD equation is not valid for people under 18 and is not reported for this group
In healthy individuals: The MDRD equation tends to underestimate normal or near-normal function; therefore, slightly low values should not be over-interpreted. eGFR values > 60 mL/min/1.73m2.are not reported in NHS Tayside

How are the results interpreted?

eGFR is used to measure the severity of kidney damage. The stages of CKD (Chronic Kidney Disease) are mainly based on measured or estimated. There are five stages but, importantly, kidney function is normal in Stage 1, and minimally reduced in Stage 2.

The KDOQI stages of kidney disease are:
Stage	GFR*	Description	Treatment Stage
1	90+	Normal kidney function but urine findings or structural abnormalities or genetic trait point to kidney disease	Observation, control of blood pressure. Routine referral only indicated if other evidence of renal disease e.g. significant proteinuria or suspicion of non-diabetic renal disease.
2	60-89	Mildly reduced kidney function, and other findings (as for stage 1) point to kidney disease	Observation, control of blood pressure. Routine referral indicated only if other evidence of renal disease e.g. significant proteinuria or suspicion of non-diabetic renal disease.
3	30-59	Moderately reduced kidney function	Observation, control of blood pressure and risk factors. Consider referral to Diabetic Renal Clinic.
4	15-29	Severely reduced kidney function	Planning for endstage renal failure. Referral to nephrology more appropriate if not stable.
5	<15	Very severe, or endstage kidney failure (sometimes call established renal failure)	Treatment choices. Immediate discussion and referral with Renal Physician.

* All eGFR values are normalised to an average surface area (size) of 1.73m2

Why is this important?

Please remember that referral for deteriorating renal function is best done early. Planning for dialysis or conservative management is easier to do while the patient is still well. Likewise, strategies to slow progression of renal failure are more effective when instituted early.