Diagnosis and Treatment of Diabetic Nephropathy SFM Didactics January 14, 2003 Carol Cordy, MD

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Diagnosis and Treatment of Diabetic Nephropathy
SFM DidacticsJanuary 14, 2003Carol Cordy, MD
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1. Why should you screen for diabetic
nephropathy?2. How should you screen for
diabetic nephropathy?3. What should you do with
the results of your screening tests?
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Why screen? Why treat?

• Prevention and treatment of diabetic nephropathy
  can reduce the incidence of end stage renal
  disease and death

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Diabetic Nephropathy and ESRD

• Diabetic nephropathy is the leading cause of end
  stage renal disease in the United States
  accounting for over 40 of dialysis patients
• The 5-year mortality rate for a dialysis patient
  is 93
• Dialysis for one patient costs over 50,000
  annually

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Epidemiology

• Type 1 Diabetic
• 25 - 45 will develop diabetic nephropathy
• 80 - 90 with microalbuminuria will progress to
  overt diabetic nephropathy in 5 - 10 years
• nearly 100 with gross proteinuria will progress
  to ESRD in 7 - 10 yrs

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Epidemiology

• Type 2 Diabetic
• 50 will have microalbuminuria at the
• time of presentation probably secondary
• to HTN
• 10-20 with microalbuminuria will
• progress to overt nephropathy
• minority populations have a 2 to 20-fold
• higher incidence of diabetic nephropathy

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Risk Factors for Diabetic Nephropathy

• Age, Race, Ethnicity
• History of microalbuminuria
• Hypertension
• Poor glycemic control
• Smoking
• Family history of nephropathy
• genetic abnormalities of ACE gene

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Stages of Diabetic Nephropathy

• Stage I Hyperfiltration - increased blood flow
  through the kidney, early renal hypertrophy
• Stage II - Glomerular lesions without clinically
  evident disease
• Stage III - Incipient nephropathy with
  microalbuminuria - alb/cr ratio .03 - .3 or
  albumin 20-200 mcg/min on timed specimen

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Stages of Diabetic Nephropathy
II
III
I
IV
V
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Stages of Diabetic Nephropathy

• Stage IV - Overt diabetic nephropathy with
  proteinuria 500 mg/24 hr
• - creatinine clearance
• Stage V End stage renal disease (ESRD)
• - creatinine clearance
• - creatinine 6mg/dl

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Stages of Diabetic Nephropathy
II
III
I
IV
V
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• Primary care physicians have the most frequent
  contact with diabetic patients and therefore have
  the greatest potential to favorably affect their
  health

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How are we doing?

• Studies show that primary care physicians screen
  only 20 of their diabetic patients for diabetic
  nephropathy

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How are we doing?

• Once screened many physicians are not sure what
  to do with the results

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Diabetic Nephropathy Algorithm

• Evidence-based approach
• Goal
• The use of the algorithm will improve renal
  function screening in the diabetic population and
  encourage the initiation of appropriate therapy
  in patients with all stages of renal disease

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Using the Algorithm
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UA (Urine Dipstick)

• Use as an initial screen for all patients
• Negative to trace proteinuria requires further
  testing for microalbuminuria
• 1 or greater proteinuria requires further
  testing to quantitate proteinuria
• Once a patient has microalbuminuria, UA (urine
  dipstick) testing for gross proteinuria may be
  adequate although yearly testing for albuminuria
  may have become standard of care

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Microalbuminuria

• Spot AM urine Alb/Cr ratio .03-.3
• Timed urine collection 20-200µg albumin/min
• 24 hour urine collection 30-300 mg albumin in 24
  hours
• 
  This is the most practical test

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Microalbumin Testing

• Factors that Cause False Positive Test
• poorly controlled diabetes
• morbid obesity
• acute illness, fever, UTI
• pregnancy, menstruation
• high protein diet
• CHF
• hematuria, major stress surgery or anesthesia

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Incipient Nephropathy

• Type 1 Diabetes
• 2 out of 3 urine tests for microalbuminuria
  (start screening 5 years after the initial
  diagnosis)
• presence of proliferative diabetic retinopathy
• 80-90 of type 1 patients with microalbuminuria
  will progress to DN

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Incipient Nephropathy

• Type 2 Diabetes
• 2 out of 3 urine tests for microalbuminuria
  (start screening at the time of diagnosis of
  diabetes)
• presence of diabetic retinopathy
• 20-30 may have diabetic nephropathy but not
  diabetic retinopathy
• 25 may have a diagnosis of nephropathy other
  than diabetic nephropathy

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Macroalbuminuria

• Spot AM urine Alb/Cr ratio greater than .3
• Timed urine collection greater than
• 200µg albumin/min
• 24 hour urine collection greater than 300 mg
  albumin in 24 hours
• If macroalbuminuria is present then test for
  gross proteinuria
• 
  

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Gross Proteinuria

• Defined as urine protein 500mg/24 hr.
• Gold standard test is
• 24 hour urine collection for total protein
  and creatinine clearance
• Can also test protein/creatinine ratio
• measures total mg protein/mg creatinine
• correlates 11 with a 24 hr urine in
  grams/24 hr
• less accurate in ARF, intersitial nephritis,
  high degrees of proteinuria

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Overt Diabetic Nephropathy

• Gold Standard is biopsy
• Diagnosis can be made by clinical history and
  exclusion of other renal disease
• Workup includes
• Renal ultrasound for size, shape, abnormalities
• 24 hour urine for total protein and creatinine
  clearance

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Treatment

• Lifestyle changes
• Lose weight
• Stop smoking
• Low salt diet for BP control
• Low protein diet?
• Glycemic Control
• Benefit in both Type 1 and Type 2 patients
• Recommended HbA1C
• (some say

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Blood Pressure Control

• Current ADA recommendations are for blood
  pressure
• Several randomized controlled trials indicate
  that improved blood pressure control decreases
  the rate of progression of renal disease in both
  type 1 and type 2 patients

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ACEs and ARBs

• Angiotensin converting enzyme inhibitors and
  angiotensin receptor blocking agents have been
  shown in animal models and in randomized
  controlled trials to improve diabetic nephropathy
• Mechanism of action - ACE-inhibitors limit
  angiotensin II production by blocking angiotensin
  converting enzyme, ARB-agents block angiotensin
  II receptors

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Questions for future studies

• Will higher doses of ACEs and ARBs improve
  outcome and decrease microalbuminuria?
• Will patients without microalbuminuria benefit
  from the use of ACEs and ARBs?
• What about other BP medications for patients who
  cannot tolerate ACEs and ARBs?
• Which of the newer oral agents for glucose
  control are also renal protective?
• Is there a place for low protein diets for
  diabetics before renal disease develops?

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Case 1

• Your first patient is a 25 year old young man
  with a 5 year history of type 1 diabetes. His
  urine dipstick is negative for protein. You check
  a spot AM urine alb/cr ratio which is .019. His
  blood pressure is 112/66. His HbA1C is 6.9.

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Which is (are) true?

• The patient has early or incipient diabetic
  nephropathy.
• The patient should maintain a HbA1C of less than
  7 to help protect his kidneys.
• You should start the patient on an ACE inhibitor
  to protect his kidneys.
• All of the above are true.

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Patient 2

• Your next patient is a 43 year old woman with a
  six year history of type 2 diabetes. A urine dip
  shows trace protein and a spot AM urine alb/cr
  ratio is .039. Her blood pressure is 135/80 and
  her HbA1C is 6.7.

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Which is (are) not true?

• You should check the patients serum creatinine
  and potassium.
• You should start the patient on an ACE inhibitor
  if her K and Cr are okay.
• You should check a 24 hour urine for total
  protein and creatinine clearance.
• The patient has overt diabetic nephropathy and
  should be referred to a nephrologist.

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Case 3

• Your last patient is a 60 year old with HTN,
  dyslipidemia and newly diagnosed type 2 diabetes.
  A urine dip shows 2 protein. He has a fever
  and his HbA1C is 10.3. His blood pressure is
  140/88. He is taking HCTZ and glipizide.

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Which is (are) true?

• You should get the patients diabetes under
  better control before rechecking his urine.
• A fever will not cause proteinuria.
• The patients blood pressure is under good
  control.
• You should check the patients potassium and
  creatinine.

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Case 3

• Three months later with exercise, metformin and
  enalapril your patients HbA1C is now 7.5 and his
  blood pressure is 135/85. A urine dip now shows
  1 protein.

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Which is (are) true?

• You should check a 24 hour urine for total
  protein and cr. cl.
• A spot AM urine albumin/creatinine ratio
  correlates well with a 24 hour urine for total
  protein
• The patient likely already has diabetic
  nephropathy and should be referred to a
  nephrologist.

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Use the Algorithm!

• Check all your diabetic patients annually for
  renal disease .
• Help your diabetic patients protect their
  kidneys by helping them keep their diabetes under
  control.
• Help your diabetic patients protect their kidneys
  by helping them keep their blood pressure under
  control.