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Screening and Management of Renal Complications

Diabetes - Screening & Management of Renal Complications

 

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Introduction

Diabetes is a common cause of renal failure and in the UK over 20% of those commencing on renal replacement have diabetes. It is more common in certain ethnic minorities (approximately 4-fold in patients from the Asian sub-continent).

The risk of development and progression of diabetic nephropathy is reduced by good control of diabetes and blood pressure.

It tends to occur after 15-20 years of Type 1 Diabetes but may be earlier in Type 2 Diabetes. Diabetic nephropathy is a serious complication and is a common cause of renal failure. After commencing dialysis diabetics have poor survival (mean 5.5 years) although the prospects can be improved by transplantation.

Effective management requires early detection and annual screening is essential.

The earliest marker for diabetic renal disease (nephropathy) is the presence of minute traces of albumin in the urine (microalbuminuria). Microalbuminuria can only be detected with sensitive and specific tests and not with normal protein urine dipsticks. Effective management of people with microalbuminuria may prevent and certainly slow the rate of progression of nephropathy.

Non Diabetic Renal Disease

It is vital to remember that patients with diabetes may have non diabetic renal problems.

Features which may be suggestive of other causes include:

sudden onset of heavy proteinuria

the presence of heavy proteinuria in the absence of diabetic retinopathy

the presence of renal impairment in the absence of proteinuria

development of proteinuria early in the course of Type 1 diabetes

microscopic haematuria

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Screening

Patients with persistent dipstick positive proteinuria may have established nephropathy which requires management in it’s own right

All patients over 12 years should be screened annually

Screening for microalbuminuria (albumin/creatinine ratio: ACR) should be performed yearly using an early morning urine sample (EMU), which has tested negative for protein on routine dipstick. A further 2 urine samples would be required to confirm a positive screen.

Correct sampling procedure is essential

A Positive ACR is defined as:

 

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>2.5mg / mmols for males

 

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>3.5mg / mmols for females

 

If 2 and/or 3 EMUs within a 1-month period are positive, this confirms microalbuminuria and the patient should be treated as High Risk Group

Any patient with confirmed microalbuminuria does not require further screening, but should have a monitoring EMU sample for ACR sent every 6 months as well as blood tests for U&Es and HBA1c

A blood sample should also be sent for serum creatinine measurement to check renal function. This can be used to calculate an estimated glomerular filtration rate (eGFR).

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Management of Microalbuminuria

Established diabetic nephropathy leads to progressive renal damage resulting in a decline in renal function and ultimately end-stage renal disease. However, treatment at the microalbuminuric stage with tight glucose and blood pressure control may prevent and certainly slow the rate of progression to nephropathy.

ACE inhibitors are first-line treatment, even in patients with normal blood pressure, as they have been shown to reduce microalbuminuria

ARB are second-line if ACE inhibitors are not tolerated

 

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Both of the above should be used with caution in women of child-bearing age and advice must be given regarding contraception

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U&E must be checked 1-2 weeks after starting or altering the dose to check for hyperkalaemia or deterioration in creatinine level, which could indicate renal artery stenosis. A rise of up to 10-15% in serum creatinine after ACE inhibitor or ARB from baseline requires a repeat check and a rise of >15% means that the ARB or ACE inhibitor should be discontinued.

 

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In case of modest hyperkalaemia without deterioration of serum creatinine a low potassium diet may allow continued use of the ACE inhibitor or ARB   (See - Diet Guideline - Proteinuria)

If ACE inhibitors or ARBs cannot be used, non-dihydropyridine calcium antagonists, such as Diltiazem, which also have antiproteinuric properties, are useful alternatives

Blood pressure target:

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<130/80mmHg

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Many patients will require 2 or more different anti-hypertensives to reach this target

 

Good diabetes control

 

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HbA1c<48 mmol/mol

Use of Metformin in Renal Impairment

NICE Guidance (2015) recommendation:

Review the dose of metformin if the serum creatinine exceeds 130 umol/litre or the estimated glomerular filtration rate (eGFR) is below 45 ml/minute

Stop the metformin if the serum creatinine exceeds 150 umol/litre or the eGFR is below 30 ml/minute

Prescribe metformin with caution for those at risk of a sudden deterioration in kidney function and those at risk of eGFR falling below 45 ml/minute

Other Therapies:

Aspirin 75mg o.d.

Statin

Smoking cessation advice

Dietetic advice

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Renal Disease – Monitoring
Monitoring is essential to assess the effectiveness of management and disease progression.
Microalbuminuria

6 monthly ACR

6 monthly U&E / eGFR

6 monthly HBA1c

Proteinuria

6 monthly U&E / eGFR

6 monthly HBA1c
6 monthly PCR (Protein Creatinine Ratio)

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Chronic Kidney Disease

The NSF for renal disease and other guidance now uses a classification for Chronic Kidney Disease (CKD) based on estimated GFR (eGFR) and clinical features. eGFR is calculated from the patient’s serum creatinine, age, gender, and ethnicity. Five stages of CKD are recognised:

Stage Description of CKD

1

Normal eGFR; eGFR >90 ml/min with other evidence* of chronic kidney damage

2

Mild impairment; eGFR 60–89 ml/min with other evidence* of chronic kidney damage

3

Moderate impairment; eGFR 30–59 ml/min (Stage 3 may also be divided into Stage 3A – eGFR 45 – 59 ml/min and Stage 3B – eGFR 30 – 44 ml/min.)

4

Severe impairment: eGFR 15–29 ml/min

5 Established renal failure (ERF): eGFR < 15 ml/min or on dialysis

 

* Other evidence of chronic kidney damage may be one of the following:

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persistent microalbuminuria

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persistent proteinuria

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persistent haematuria (after exclusion of other causes, eg urological disease)

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structural abnormalities of the kidneys demonstrated on ultrasound scanning or other radiological tests (eg polycystic kidney disease, reflux nephropathy)

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biopsy-proven chronic glomerulonephritis (most of these patients will have microalbumuria or proteinuria, and/or haematuria)

Proteinuria:
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Remains the diagnostic hallmark of true kidney disease and, in general terms, the greater the proteinuria the greater the likelihood of progression.

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ACEI/ARB are useful for their antiproteinuric effects.

Both ACR and PCR are now in common usage. Approximate equivalent values:

                 
  Proteinuria   ACR(mg/mmol)   PCR  (mg/mmol)   Urine Protein(g/24h) for reference  
                 
                 
  Mild   <30   <50   <0.5  
                 
                 
  Significant   >70   >100   >1.0  
                 
                 

 

Nephrotic Range   >200   >300   >3.0  
 

 

 

 

 

 

     

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Referral to a Nephrologist

The majority of diabetic patients with CKD 1-3 and some with Stage 4 CKD will normally be managed in primary care.

People should usually be referred for specialist assessment if any of the following apply:

Suspicion of the presence of non-diabetic renal disease (see above)

 

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proteinuria and persistent invisible (microscopic) haematuria

 

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presumed diabetic nephropathy but no retinopathy

Stage 4 and 5 CKD

Earlier stages of CKD with any of the following

 

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heavy proteinuria (ACR ≥70 mg/mmol, PCR >100 mg/mmol) unless already appropriately treated

 

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proteinuria (ACR ≥30 mg/mmol, PCR >50mg/mmol) together with haematuria

 

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rapidly declining eGFR (>5 ml/min/1.73m2 in one year)

 

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difficult to control hypertension

 

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suspected co-existent renal artery stenosis.

Experience locally has shown that many diabetic patients referred to the nephrology clinic already have their management optimised with regard to lipids, glycaemic and BP control including the use of ACEIs and ARBs.

If there are concerns, seeking preliminary advice from a nephrologist rather than requesting a formal appointment can be a better use of resources and spare the patient an unnecessary visit. Currently advice, as opposed to an appointment is offered in 50% of referrals received. Please do not use the Choose & Book process for requests for advice.

Advice for referrals by clinicians can be emailed to the Renal Team at Lister Hospital Stevenage - renalreferraladvice.enh-tr[at]nhs.net

 

Pre-Investigation

The following should be included with the referral:

Timeline of creatinine/eGFR

Details of co-morbid conditions, particularly IHD, PVD and associated procedures

Urological and smoking history

Urine stix for blood/protein, quantification of proteinuria by ACR or PCR

List medications particularly ACEI and ARB

Any observed increase in creatinine with ACEI or ARB

History of nephrotoxic drugs - NSAID, lithium

Weight, BMI*

Results of imaging – renal ultrasound **

*

obesity can contribute significantly to proteinuria

**

If time permits a renal ultrasound is useful for kidney size and evidence of obstruction. This information can often allow a ‘one-stop’ renal OP visit.

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Samples for Microalbuminuria or Proteinuria

Microalbuminuria

Early morning specimen of urine

Negative for protein on routine dipstix testing

False positive results can be caused by infection, fever, menstruation, recent exercise

If the protein dipstick is positive an MSU should be sent for C&S to exclude a urinary tract infection. If no UTI is present, a 24 hour urine collection should be obtained for proteinuria.

If a UTI is present, this should be treated and the ACR screen repeated.

If first sample is positive then 2 confirmatory samples should be sent within a month: if 2 out of 3 are positive, microalbuminuria can be diagnosed.

Labelling:

 

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ACR 1st screen

 

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ACR 2nd screen

 

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ACR 3rd screen
  • ACR monitoring

Ensure a separate card is filled for each test and separate cards should be filled for blood and urine tests.

Proteinuria
Can be assessed by measuring the Protein Creatinine ratio on a random urine sample.  24 Hour collections are no longer necessary.
   

Regional Renal Service

  Renal service in Bedfordshire are provided by the team from the East & North Herts Trust who run satellite units in Luton and Bedford.
Renal Service
  Non urgent specialist advice for health care professionals can be accessed by e-mail: renalreferraladvice.enh-tr.@nhs.net

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Useful External Links & Resources
The Renal Association - UK
Renal Unit (Edinburgh) GP Information
Renal Unit (Edinburgh) Patient Information

NICE | Management of Type 2 Diabetes - (2015)

PDF File Fact Sheet - Information about Microalbuminuria
PDF File Fact Sheet - Microalbuminuria Testing
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