• 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
  • Send a random urine sample to the biochemistry lab for urine albumin creatinine ratio (ACR)
  • Check Creatinine and electrolytes(eGFR).

 

Urine testing - what samples are needed?

  • Since January 2010, the lab has 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. 
  • Routine point of care dipstick testing is not recommended unless the patient has symptoms of urinary tract infection, or for guidance of investigations as to the cause of renal impairment (see below)
  • 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

 

Patient Group

Sex

Albumin/Creatinine

Ratio (mg/mmol)

Protein/Creatinine

Ratio (mg/mmol)

Diabetic

Male

 

 

 

Female

 

 

Non- Diabetic

Both

 

 

 

 

 

If ACR = 30 to 69 mg/mmol,

confirm result on an  EMU

If PCR = 50 to 99 mg/mmol,

confirm result on an EMU

*If ACR > 70 mg/mmol creatinine or PCR > 100mg/mmol creatinine, consider referral to the Combined Diabetic Renal Clinic

 EMU = early morning urine specimen

 ACR = Albumin Creatinine Ratio

 PCR = Protein Creatinine Ratio 

 

Back to the topBack to the top of this page

 

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 estimateonly.  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:
StageGFR*      DescriptionTreatment 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   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.

Back to the topBack to the top of this page

 

Investigation of CKD in People with Diabetes - Flow Chart

 

 

Management of Diabetic Renal Disease

  1. Improve glycaemic control (Target HbA1c <  53 mmol/mol or 7.0%)
  2. Encourage smoking cessation
  3. Apply aggressive targets for control of hypertension
    • Type 1 diabetes
    • Type 2 diabetes
  4. Consider introduction of an ACE Inhibitor in Type 1 patients with microalbuminuria or overt proteinuria, even if blood pressure is within target.
    • Remember the possibility of teratogenesis in females of child-bearing age.
  5. Consider introduction of an ACE Inhibitor or ARB, as 1st-line therapy, in Type 2 patients with microalbuminuria or proteinuria. Remember the possibility of co-existing renovascular disease. See Handbook section on Screening and Management of Cardiovascular Risk.
  6. In all patients, co-existing cardiovascular risk factors should be managed aggressively.
    • Consider starting statin therapy as per handbook and Aspirin 75mg daily

 

Guidance on use of Metformin in Diabetic Patients with CKD

 

Metformin therapy may be associated with lactic acidosis and this is more likely to occur in patients with renal impairment. However metformin per se is not nephrotoxic.

Estimated Glomerular Filtration Rate (eGFR) is now routinely calculated and reported by NHS Tayside Biochemical Medicine Labs to aid in the quantification of renal function. In the light of this we have developed the following strategy with colleagues in nephrology:

Action should be taken as outlined below if the eGFR is abnormal on 2 consecutive results at least 6 weeks apart

  • eGFR > 50 no need to alter Metformin.
  • eGFR 30-50 reduce Metformin dose to 500mg BD
  • eGFR < 30 stop metformin

It is worth remembering the following:

  • This is a guideline and as such needs to be interpreted in the light of an individual patient's other co morbidities e.g. heart failure, significant COPD etc, which if present might preclude ongoing therapy at higher eGFR values
  • If Metformin is to be reduced or discontinued then it will be necessary to review the need for additional hypoglycaemic therapy at an early stage
  • In patients who have had a lower extremity amputation, the eGFR may not be truly representative of the renal status and other methods of determining this should be used e.g. measurement of glomerular filtration rate.

 

Back to the topBack to the top of this page


Guidelines for the Combined Diabetes Renal Clinic at Ninewells Hospital and Perth Royal Infirmary

 

Aims of the clinic

  • To identify, investigate and manage renal disease in patients with diabetes at an early stage, in order to slow the progression to renal failure.
  • To institute aggressive management of glycaemic control and co-existing cardiovascular risk factors where feasible.
  • To screen for metabolic bone disease and renal anaemia and initiate treatment as necessary.
  • To refer onwards to the Low Renal Clearance Clinic in the pre-dialysis phase.

 

Referral criteria to clinic

  • Estimated GFR < 60ml/min in Type 1 diabetes
  • Estimated GFR < 40ml/min in Type 2 diabetes
  • Significant Proteinuria (ACR > 70 or PCR > 100) regardless of diabetes type, in the absence of infection.
  • ACR > 35 or PCR > 50 in spite of ACE inhibitor or ARB therapy.
  • Significant deterioration in creatinine following use of ACE inhibitor (increase of 20% above baseline value)
  • Suspicion of non-diabetic renal disease (especially if haematuria present) (i.e. ACR 30 - 69)
  • Patients with persistent proteinuria that is less then the above should be referred to the routine hospital Diabetes Clinic. If in doubt, please discuss with the diabetes team.

 

Investigations prior to referral

It is helpful to have requested some of the following, where relevant, when patients are referred to this clinic. However, the results of investigations do not need to be available when the referral is made. If in doubt, please discuss with Dr Schofield/Dr Severn (Ninewells) or Dr Pearson/Dr Henderson (PRI).

  • Full U&E’s
  • Recent dipstick urinalysis
  • Renal ultrasound
  • Immunology screening (ANA, Immunoglobulins, ANCA, CRP) especially if haematuria present
  • Myeloma screening (plasma protein electrophoresis/urine for Bence Jones protein) in patients aged over 50.

 

Investigation of isolated microscopic haematuria

  • In patients aged
  • In older patients i.e. aged 50 and over, this is more likely to represent disease of the lower urinary tracts. These patients should have a renal USS and if this is negative, refer to the Urology team. 

 

Discharge to Low Renal Clearance Clinic (Pre-dialysis patients)

Patients with estimated GFR < 25ml/min (approx.) will be referred to the low GFR clinic for management of anaemia and for counselling regarding possible dialysis. Patients usually attend this clinic every 6-8 weeks. In view of this, they are usually discharged from the Combined Diabetic Renal Clinic and referred back to attend a routine hospital diabetes clinic.

 

Management of Anaemia in Chronic Kidney Disease

See Renal Dialysis Unit Guidelines

 

Back to the topBack to the top of this page