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Diabetic Renal Disease

Renal Disease

Diabetic Kidney Disease

  • Diabetic kidney disease is a chronic complication of diabetes due to longstanding effect on glomerulus causing impairment of renal function.

  • 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 diagnosis is clinical, based of a triad (or quartet) of

  • Progressive rise in blood pressure

  • Progressive rise in albuminuria and

  • Progressive fall in glomerular filtration rate (GFR) with an

  • Associated progressive increase in cardiovascular risk

The possibility of non-diabetic renal disease should be considered if atypical features such as haematuria or rapid progression are present, or if retinopathy is absent.

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Annual renal function testing

Perform tests annually to assess renal function regardless of the presence of nephropathy

  • Measure Urine Albumin/Creatinine Ratio (ACR)

    • Random spot urine samples are valid (prefer morning)

    • Threshold levels

      • Microalbuminuria - the practical use of gender specific thresholds of 2.5mg/mmol in men and 3.5mg/mmol in women are limited and we use a convenient single threshold of 3.5mg/mmol as is recommended by the American Diabetes Association.

      • Macroalbuminuria/overt proteinuria – urine ACR >30mg/mmol or presence of dipstick proteinuria

    • Routine testing for urinary infection not needed unless symptomatic

    • Request for re-testing to confirm microalbuminuria is met with poor compliance and is of limited clinical significance and hence not routinely recommended 

  • Measure serum Creatinine and

  • Estimate Glomerular Filtration Rate (eGFR) using the MDRD equation

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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

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Macroalbuminuria / Overt 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 and a threshold of 30mg/mmol is the equivalent level for dipstick proteinuria.

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Estimated GFR (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 an MDRD equation which is robust and accurate for estimating impaired renal function. GFR in health individuals is approximately 100mL/min/1.73m2.

Caveats of eGFR

  • It is vital to remember that eGFR provides an estimate only. A 20% fall in eGFR is almost certain to reflect an important change. 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, 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. 

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 GFR. There are five stages but, importantly, kidney function is normal in Stage 1, and minimally reduced in Stage 2.

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Chronic Kidney Disease Staging (KFOQI)

Chronic Kidney Disease is staged based on the estimated GFR and is relevant for any aetiology of chronic kidney disease.

Stage

eGFR (ml/min/1.73m2)

Description

1

90+

Normal kidney function but urine findings or structural abnormalities or genetic trait pointing to kidney disease

2

60-89

Mildly reduced kidney function and other findings (as for stage 1) point to kidney disease

3A
3B

45-59
30-44

Moderately reduced kidney function

4

15-29

Severely reduced kidney function

5

<15 or dialysis

Very severe or end stage kidney failure

Diabetic chronic kidney disease however is dictated by not just the eGFR but also on the albuminuria status. Please refer to Diabetic Kidney Disease Likelihood table based on various combinations of albuminuria and eGFR stages.

The possibility of non-diabetic renal disease should be considered if atypical features such as haematuria or rapid progression are present, or if retinopathy is absent.

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Diabetic Kidney Disease Likelihood

Diabetic Kidney Disease (DKD) likelihood according to albuminuria and eGFR.

 

eGFR (ml/min)

 

CKD stage

Albuminuria

Normoalbuminuria

Microalbuminuria

Proteinuria

>60

1 + 2

At risk

Possible DKD

Likely DKD

45-59

3A

Unlikely DKD*

Possible DKD

Likely DKD

30-44

3B

Unlikely DKD*

Unlikely DKD*

Likely DKD

15-29

4

Unlikely DKD*

Unlikely DKD*

Likely DKD

<15

5

Unlikely DKD*

Unlikely DKD*

Likely DKD

*  consider non-diabetic etiologies and nephrology opinion

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eGFR ≥60 and Normoalbuminuria

Primary prevention of Diabetic Nephropathy (prevention of microalbuminuria)

Management

  • Manage in primary care setting

  • Annual monitoring of renal function

  • Optimise glycaemic control

    • HbA1c target of 53mg/mmol (DCCT 7%) if practical and safe

  • Optimise blood pressure control

    • Systolic BP target of <140mm Hg

    • Consider ACE inhibitor/Angiotensin receptor blocker as first choice

    • Step titrate to maximum tolerated dose

    • Consider multiple anti-hypertensives to achieve targets

  • Address appropriate cardiovascular risk factors

    • Lifestyle – Diet, Exercise, weight management

    • Address smoking

    • Lipid profile and consider statin therapy as per risk factors

Referral criteria

Specialist referral indicated if non-diabetic kidney disease strongly suspected

The possibility of non-diabetic renal disease should be considered if atypical features such as haematuria or rapid progression are present, or if retinopathy is absent.

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eGFR ≥60 and Microalbuminuria or Proteinuria

Management

  • Manage in primary care setting

  • Annual monitoring of renal function

  • Optimise blood pressure control

    • Systolic BP target of <130mm Hg if practical

    • ACE inhibitor as first choice (Angiotensin blockers if intolerant)

    • Step titrate to maximum tolerated dose

    • Majority need multiple anti-hypertensives to achieve targets

  • Optimise glycaemic control

    • HbA1c target of 53mg/mmol (DCCT 7%) if practical and safe

  • Address appropriate cardiovascular risk factors

    • Lifestyle – Diet, Exercise, weight management

    • Address smoking

    • Lipid profile and consider statin therapy as per risk factors

Referral criteria

Consider referral to specialist diabetes service if persistent significant proteinuria (ACR >35mg/mmol) despite optimal BP and ACE/ARB inhibition)

The possibility of non-diabetic renal disease should be considered if atypical features such as haematuria or rapid progression are present, or if retinopathy is absent.

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eGFR 45-60 and Normoalbuminuria

  • Explore history for other reasons of CKD and instigate relevant investigations if appropriate

  • In the elderly, isolated and non-progressive eGFR of 45-60 is unlikely to indicate CKD

Management

  • Manage in primary care setting

  • Annual monitoring of renal function

  • Optimise glycaemic control

    • HbA1c target of 53mg/mmol (DCCT 7%) if practical and safe

  • Optimise blood pressure control

    • Systolic BP target of <140mm Hg

    • Consider ACE inhibitor/Angiotensin receptor blocker as first choice

    • Step titrate to maximum tolerated dose

    • Consider multiple anti-hypertensives to achieve targets

  • Address appropriate cardiovascular risk factors

    • Lifestyle – Diet, Exercise, weight management

    • Address smoking

    • Lipid profile and consider statin therapy as per risk factors

Referral criteria

Specialist referral indicated if non-diabetic kidney disease strongly suspected

The possibility of non-diabetic renal disease should be considered if atypical features such as haematuria or rapid progression are present, or if retinopathy is absent.

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eGFR 45-60 and and Microalbuminuria or Proteinuria

Management

  • Manage in primary care setting

  • Bi-annual monitoring of renal function

  • Optimise blood pressure control

    • Systolic BP target of <130mm Hg if practical

    • ACE inhibitor as first choice (Angiotensin blockers if intolerant)

    • Step titrate to maximum tolerated dose

    • Majority need multiple anti-hypertensives to achieve targets

  • Optimise glycaemic control

    • HbA1c target of 53mg/mmol (DCCT 7%) if practical and safe

  • Address appropriate cardiovascular risk factors

    • Lifestyle – Diet, Exercise, weight management

    • Address smoking

    • Lipid profile and consider statin therapy

Referral criteria

Consider referral to specialist diabetes service if persistent significant proteinuria (ACR >35mg/mmol) despite optimal BP and ACE/ARB inhibition)

The possibility of non-diabetic renal disease should be considered if atypical features such as haematuria or rapid progression are present, or if retinopathy is absent.

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eGFR 30-45 and Normoalbuminuria

  • Unusual for Diabetic Kidney disease

  • Explore history for other reasons of CKD and instigate relevant investigations

  • Refer to nephrology service for further renal investigations and management

Management

  • Manage diabetes in primary care setting unless sub-optimal control of metabolic and cardiovascular risk factors

Quarterly monitoring of renal function

  • Optimise glycaemic control

    • HbA1c target of 53mg/mmol (DCCT 7%) if practical and safe

    • Metformin reasonably safe to continue if eGFR >30

      • Consider reduced dose (500 mg BD)

      • Avoid during periods of inter-current illnesses (‘sick day rules’)

  • Optimise blood pressure control

    • Systolic BP target of <140mm Hg

    • Consider ACE inhibitor/Angiotensin receptor blocker as first choice

    • Step titrate to maximum tolerated dose

    • Consider multiple anti-hypertensives to achieve targets

  • Address appropriate cardiovascular risk factors

    • Lifestyle – Diet, Exercise, weight management

    • Address smoking

    • Lipid profile and consider statin therapy as per risk factors

Referral criteria

Refer to nephrology service for further renal investigations and management

The possibility of non-diabetic renal disease should be considered if atypical features such as haematuria or rapid progression are present, or if retinopathy is absent.

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eGFR 30-45 and Microalbuminuria or Proteinuria

Management

  • Diabetes Specialist team involvement to agree and update appropriate management plan

  • Bi-annual monitoring of renal function

  • Optimise blood pressure control

    • Systolic BP target of <130mm Hg if practical

    • ACE inhibitor as first choice (Angiotensin blockers if intolerant)

    • Step titrate to maximum tolerated dose

    • Majority need multiple anti-hypertensives to achieve targets

  • Optimise glycaemic control

    • HbA1c target of 53mg/mmol (DCCT 7%) if practical and safe

    • Metformin reasonably safe to continue if eGFR >30

      • Consider reduced dose (500 mg BD)

      • Avoid during periods of inter-current illnesses (‘sick day rules’)

       

  • Avoid high protein intake (>1g/kg/d)

  • Address appropriate cardiovascular risk factors

    • Lifestyle – Diet, Exercise, weight management

    • Address smoking

    • Lipid profile and consider statin therapy

Referral criteria

Refer to specialist diabetes service if metabolic and cardiovascular risk factors are sub optimally controlled

The possibility of non-diabetic renal disease should be considered if atypical features such as haematuria or rapid progression are present, or if retinopathy is absent.

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GFR 15-30 and Normoalbuminuria

  • Unlikely to be Diabetic Kidney disease

  • Explore history for other reasons of CKD and instigate relevant investigations

  • Refer to nephrology service for further renal investigations and management

Management

  • Refer to Nephrology services

  • Refer to Diabetes specialist service to update diabetes care plan

  • Quarterly monitoring of renal function

  • Optimise blood pressure control

    • Systolic BP target of <130mm Hg if practical

    • ACE inhibitor as first choice (Angiotensin blockers if intolerant)

    • Step titrate to maximum tolerated dose

    • Watch for hyperkalemia and modify choice accordingly

    • Majority need multiple anti-hypertensives to achieve targets

  • Optimise glycaemic control

    • HbA1c target of 53mg/mmol (DCCT 7%) if practical and safe

    • Consider risk and enhance education for hypoglycaemia

    • Metformin and long acting Sulfonylurea unsafe.

    • Avoid Pioglitazone if at risk of fluid retention and weight gain

    • DPP-4 inhibitors safe but dose reduction required for individual agents.

    • GLP analogues to be avoided due to risk of intolerance.

    • Consider insulin with choice of regime dictated by profile, hypoglycaemia risk, uremic symptoms etc.

  • Address appropriate cardiovascular risk factors

    • Lifestyle – Diet, Exercise, weight management

    • Smoking

    • Lipid profile and consider statin therapy

  • Dietetics review

    • Salt and fluid restriction

    • Potassium restriction

  • Evaluate and correct anaemia

  • Evaluate and correct Renal bone disease

  • Pre-dialysis work up/counselling

    • Vascular access if progressive

    • Consider pre-emptive transplantation if progressive

The possibility of non-diabetic renal disease should be considered if atypical features such as haematuria or rapid progression are present, or if retinopathy is absent.

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eGFR 15-30 and Microalbuminuria or Proteinuria

Management

  • Should be managed by diabetes specialist team in the diabetes renal clinic for intensive risk factor intervention and follow up

  • Routine case-based MDT discussion with nephrology to agree and update renal plans

  • Referral to nephrology if unstable

  • Quarterly monitoring of renal function

  • Optimise blood pressure control

    • Systolic BP target of <130mm Hg if practical

    • ACE inhibitor as first choice (Angiotensin blockers if intolerant)

    • Step titrate to maximum tolerated dose

    • Watch for hyperkalemia and modify choice accordingly

    • Majority need multiple anti-hypertensives to achieve targets

  • Optimise glycaemic control

    • HbA1c target of 53mg/mmol (DCCT 7%) if practical and safe

    • Consider risk and enhance education for hypoglycaemia

    • Metformin and long acting Sulfonylurea unsafe.

    • Avoid Pioglitazone if at risk of fluid retention and weight gain

    • DPP-4 inhibitors safe but dose reduction required for individual agents.

    • GLP analogues to be avoided due to risk of intolerance.

    • Consider insulin with choice of regime dictated by profile, hypoglycaemia risk, uremic symptoms etc.

  • Address appropriate cardiovascular risk factors

    • Lifestyle – Diet, Exercise, weight management

    • Smoking

    • Lipid profile and consider statin therapy

  • Dietetics review

    • Salt and fluid restriction

    • Potassium restriction

  • Evaluate and correct anaemia

  • Evaluate and correct Renal bone disease

  • Pre-dialysis work up/counselling

    • Vascular access if progressive

    • Consider pre-emptive transplantation if progressive

The possibility of non-diabetic renal disease should be considered if atypical features such as haematuria or rapid progression are present, or if retinopathy is absent.

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eGFR <15 or renal replacement therapy

Management

  • Should remain under active follow up of Renal service

  • Patients on renal replacement therapy should have biannual diabetes reviews

    • For haemodialysis patients, this will be proactively provided by Wolverhampton Diabetes Service at New Cross and Pond lane units

    • For patients at other renal satellite units, the relevant local specialist diabetes service will provide diabetes follow up

    • For patients on peritoneal dialysis, such follow up will be provided under a combined Diabetes-PD clinic setting 

  • Quarterly monitoring of renal function

  • Optimise blood pressure control

    • No clear guidance on BP target for patients on dialysis – pragmatic systolic BP target of <140mm Hg is sought

    • Fluid and salt balance crucial to BP control

    • Medications may be required if this proves insufficient

    • ACE inhibitor as first choice (Angiotensin blockers if intolerant)

    • Step titrate to maximum tolerated dose

    • Watch for hyperkalemia and modify choice accordingly

  • Optimise glycaemic control

    • HbA1c target of 53mg/mmol (DCCT 7%) if practical and safe

    • Consider risk and enhance education for hypoglycaemia

    • Metformin and long acting Sulfonylurea unsafe.

    • Avoid Pioglitazone if at risk of fluid retention and weight gain

    • DPP-4 inhibitors safe but dose reduction required for individual agents.

    • GLP analogues to be avoided due to risk of intolerance.

    • Consider insulin with choice of regime dictated by profile, hypoglycaemia risk, uremic symptoms etc.

  • Address appropriate cardiovascular risk factors

    • Lifestyle – Diet, Exercise, weight management

    • Smoking

    • Lipid profile – evidence for statin therapy in dialysis patients lacking

  • Dietetics review

    • Salt and fluid restriction

    • Potassium restriction

  • Preventative foot care

  • Evaluate and correct anaemia

  • Evaluate and correct Renal bone disease

  • Vascular access

  • Dialysis and transplant work up/counselling

The possibility of non-diabetic renal disease should be considered if atypical features such as haematuria or rapid progression are present, or if retinopathy is absent.

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Guidelines for the Dedicated Diabetes Renal Clinic

Aims of the clinic

  • To identify, investigate and manage renal disease in patients with diabetes at in order to slow the progression to end stage renal failure.

  • To have case based MDT discussion with nephrology to plan for pre-emptive transplantation and/or prepare for renal replacement therapy.

  • 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

  • All diabetes patients with eGFR15-30ml/min

  • Estimated GFR 30-45ml/min if medical risk factors are not optimised

  • Irrespective of eGFR category, patients with ACR > 35 in spite of optimal BP and/or maximal ACE/ARB inhibition.

  • Significant deterioration in creatinine following use of ACE inhibitor (increase of 20% above baseline value)

Discharge criteria

  • Patients deemed unsuitable for renal replacement therapy (conservative ESRF patients) whose medical risk factors are safely addressed can be discharged back to the community team

  • Patients with stable eGFR (>30ml/min) whose medical risk factors are optimised can be discharged back to primary care.

  • Patients with eGFR < 15ml/min (approx.) will be referred to the nephrology for counselling regarding possible dialysis.

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Governance Framework

Information in the diabetes and the renal registry systems will be periodically shared/merged and workflows created for the various CKD stages.
Dedicated case based MDT discussions with input from the renal team to update the diabetes and renal care plan for CKD 4 and 5 stage patients.
Annual governance reports to be presented

  • Report of Diabetes CKD prevalence and risk factor management

  • Report of Renal care plan documentation and foot care status among patients with CKD stages 4 & 5

  • Report of renal and simultaneous kidney-pancreas transplantation patients

  • Report of updated diabetes care plans for patients with ESRF managed conservatively