DM & CKD

Dr. Shahrzad ShahidiProfessor of Nephrology

Isfahan University of Medical Sciences

CKD Kidney damage for ≥ 3 months, defined by

structural or functional abnormalities of the kidney, ± decreased GFR, manifest by either:

Albuminuria (AER ≥ 30 mg/24 hs; ACR ≥ 30 mg/g Cr) Urine sediment abnormalities Electrolyte & other abnormalities due to tubular

disorders Abnormalities detected by histology Structural abnormalities detected by imaging Hx of kidney transplantation GFR < 60 mL/min/1.73 m2 for ≥ 3 months ± kidney

damage

3

If no other markers of

kidney disease, no CKDModerately increased

riskHigh risk

Very high risk

4

Diabetic Nephropathy

Incidence of ESRD Resulting from Primary

Diseases (1998)

43%

23%

12%

3%

19%

Diabetes

Hypertension

Glomerulonephritis

Cystic Kidney

Other Causes

Over 40% of new cases of end-stage renal disease (ESRD) are attributed to diabetes.

The 5-year mortality rate for a

dialysis patient with diabetic

nephropathy is 93%.

Dialysis for one patient costs

over $50,000 annually.

Diabetic NephropathyDN occurs in 35-40% of patients with

type I diabetes (IDDM) whereas it occurs only in 15-20% of patients with type II diabetes (NIDDM).

Definition or Criteria for diagnosis of DN Presence of persistent proteinuria in sterile

urine of diabetic patients with concomitant diabetic retinopathy & HTN.

Stages of Diabetic Nephropathy

020406080

100120140160180

0 5 10 15 20 25 30

Duration of Diabetes

GF

R

III

III

IV

V

Nephropathy Risk Factors

DM Type & DurationPoor diabetic controlHTNRace (Aboriginal > Indian > Caucasian)SmokersFamily history

Nephropathy Risk Factors

ModifiableHbA1c, BP & total cholesterol Obesity, smoking

Non-modifiableAge, ethnicity

Screening for Diabetic Nephropathy

Test When Normal Range

BloodPressure1

Each office visit <130/80 mm/Hg

UrinaryAlbumin1

Type 2: Annuallybeginning at diagnosisType 1: Annually, 5-yearspost-diagnosis

<30 mg/day<20 g/min<30 g/mgcreatinine

1ADA Diabetes Care 27

Screening Measurements of urinary ACR in a spot urine sample.

Measurement of serum Cr & estimation of GFR.

How are we doing?

Studies show that primary care physicians screen only 20% of their

diabetic patients for diabetic nephropathy

MicroalbuminuriaSpot AM urine: Alb/Cr ratio 30-300

mg/g Cr*Timed urine collection: 20-200µg

albumin/min24 hour urine collection: 30-300 mg

albumin in 24 hours

*This is the most practical test

Incipient Nephropathy

IDDM2 out of 3 urine tests + for microalbuminuria Presence of proliferative diabetic retinopathy 80-90% of type 1 patients with microalbuminuria will progress to DN

Incipient Nephropathy

NIDDM2 out of 3 urine tests + for

microalbuminuria (start screening at the time of diagnosis of DM)

Presence of diabetic retinopathy20-30% may have diabetic nephropathy

but not diabetic retinopathy25% may have a diagnosis of

nephropathy other than diabetic nephropathy

Q. Which features are typical of diabetic CKD at presentation ?

Haematuria NoSmall scarred kidneys NoProgress to ESKD in <2yrs NoAssociated retinopathy Yesβ-blockers better than ACE-I Rx No

Other cause(s) of CKD should be considered in the presence

of any of the following circumstances:

Absence of diabetic retinopathyLow or rapidly decreasing GFRRapidly increasing Pruria or nephrotic

syndromeRefractory HTNPresence of active urinary sedimentSigns or symptoms of other systemic disease>30% reduction in GFR within 2-3 ms after

initiation of an ACE I or ARB.

Treatment of Diabetic Nephropathy (cont.)

Glycemic Control Preprandial plasma glucose 90-130 mg/dl

A1C ~ 7.0%Peak postprandial plasma glucose <180

mg/dl

Self-monitoring of blood glucose (SMBG)Medical Nutrition Therapy

Target dietary Pr intake for people with DM & CKD stages 1-4 should be the RDA of 0.8 g/kg/d. 

Management of Hyperglycemia & General

Diabetes Care in CKDTarget HbA1c of ~ 7.0% to prevent or

delay progression of the microvascular complications of DM, including DKD.

Not treating to an HbA1c target of <7.0% in patients at risk of hypoglycemia.

Target HbA1c be extended above 7.0% in individuals with co-morbidities or limited life expectancy and risk of hypoglycemia.

Metformin in CKDNo hypoglucemia or weight gain InexpensiveBUT:

Renally-excreted Excess doses → anorexia, diarrhea Dose adjust to GFR: 2g to 250mg/day Protocol says

eGFR 30 – 45 max 1gm/day Cease when eGFR <30 but…

Risk of fatal lactic acidosis if unwell

Management of Dyslipidemia in Diabetes &

CKDUsing LDL-C lowering medicines, such

as statins or statin/ezetimibe combination, to reduce risk of major atherosclerotic events in patients with diabetes & CKD, including those who have received a kidney transplant.

Not initiating statin therapy in patients with diabetes who are treated by dialysis

Management of Albuminuria in Normotensive Patients with

Diabetes

Not using an ACE-I or an ARB for the primary prevention of DKD in normotensive normoalbuminuric patients with diabetes.

Using an ACE-I or an ARB in normotensive patients with diabetes & albuminuria levels >30 mg/g Cr who are at high risk of DKD or its progression.

BP management inCKD ND patients with DM

Adults with DM & CKD ND with urine albumin excretion < 30 mg/d whose office BP is consistently > 140 mmHg systolic or > 90 mmHg diastolic be treated with BP lowering drugs to maintain a BP that is consistently ≤140 mmHg systolic & ≤ 90 mmHg diastolic.

Adults with DM & CKD ND with urine albumin excretion > 30 mg/d whose office BP is consistently >130 mmHg systolic or > 80 mmHg diastolic be treated with BP lowering drugs to maintain a BP that is consistently ≤130 mmHg systolic & ≤ 80 mmHg diastolic.

ARB or ACE-I be used in adults with diabetes & CKD ND with urine albumin excretion of ≥ 30 mg/d.

Diabetes & ESRD

Reducing insulin requirementsDifficult vascular accessAccelerated macrovascular diseaseAdvanced microvascular diseaseFrequent sepsisSilent ischaemia2-3 x death rate vs non-DM patients

How can DM effect Dialysis?

Autonomic neuropathy – may suffer hypotension increased by large fluid shift in HD

Uncontrolled BS – may absorb some glucose in PD fluid

Severe PVD – difficult to get vascular access for HD

PVD may also affect peritoneum & reduce PD success

Increased risk of infections – problem in both Transplants – new kidneys develop nephropathy,

hence good glycaemic control important

Case #1Your first pient is a 25 y old young

man with a 5 year Hx of type 1 DM.His urine dipstick is negative for Pr. Spot AM urine Alb/Cr ratio is 19 mg/g Cr.

His BP is 112/66 mmHg. His HbA1C is 6.9%.

Which is (are) true?

1. The patient has early or incipient diabetic nephropathy.

2. The patient should maintain a HbA1C of less than 7 to help protect his kidneys.

3. You should start the patient on an ACE inhibitor to protect his kidneys.

4. All of the above are true.

Patient #2 43 y old woman with a 6 year

Hx of type 2 DM. A urine dipstich shows trace PrSpot AM urine ACR 390 mg/g Cr

BP is 135/80 HbA1C is 6.7%

Which is (are) not true?

1. You should check the patient’s serum Cr & K.

2. You should start the patient on an ACEI if her K & Cr are okay.

3. You should check a 24 hour urine for total Pr & Cr clearance.

4. The patient has overt diabetic nephropathy & should be referred to a nephrologist.

Case #360 y old man with HTN, dyslipidemia

& newly diagnosed type 2 DM. A urine dip shows 2+ Pr He has a fever & his HbA1C is 10.3%

BP is 140/88 He is taking HCTZ & Glipizide

Which is (are) true?

1. You should get the patient’s diabetes under better control before rechecking his urine.

2. A fever will not cause proteinuria.3. The patient’s BP is under good

control.4. You should check the patient’s K

& Cr.

Case #3

3 months later with exercise, metformin & Enalapril your patient’s HbA1C is now 7.5 & his BP is 135/85.

A urine dip now shows 1+ protein.

Which is (are) true?

1. You should check a 24 hour urine for total Pr & Cr. cl.

2. A spot AM urine ACR correlates well with a 24 hour urine for total Pr

3. The patient likely already has diabetic nephropathy & should be referred to a nephrologist.

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 BP under control.