PROTECTING THE KIDNEY IN DIABETES

Rey Jaime M. Tan MD, FPCPClinical Associate Professor

University of the Philippines College of MedicineSection of Nephrology, Department of Medicine

UP-Philippine General Hospital

OUTLINE

How does the kidney function?

How common is Diabetic Kidney Disease (DKD)?

What are the stages of DKD?

How can DKD be prevented?

How can the progression of DKD to Chronic Kidney Disease (CKD) be delayed?

The kidney

The kidney

Filters the blood

The kidney

Filters the blood

Reabsorbs all necessary nutrients in the blood

The kidney

Filters the blood

Reabsorbs all necessary nutrients in the blood

Excretes all waste products in the urine

The kidney

The kidney

Involved in synthesis of hormones i.e. vitamin D, erythropoietin etc.

The kidney

Involved in synthesis of hormones i.e. vitamin D, erythropoietin etc.

Maintains balance in electrolytes, acids and bases

The nephron

Functional unit of the kidney

1,000,000 nephrons per kidney

Diabetic Kidney DiseaseA Complication of Diabetes

DiabeticNeuropathy

Leading cause of non-traumaticlimb amputations60% new cases/yr

Stroke

2 to 4-foldincrease in stroke

DiabeticRetinopathy

Leading cause ofblindness in adults24000 new caseseach year in US

DiabeticNephropathy

Leading cause ofend-stage renaldisease in adults44% new cases/yr

CardiovascularDisease

8 out of 10 diabeticpatients die fromcardiovascular events5-10 year reductionin life expectancy

NIDDK, National Diabetes Statistics fact sheet. HHS, NIH, 2006.

Natural History of Type 2 Diabetic Kidney Disease

Onset of diabetes

Functional changes*

Proteinuria

End-stage renal disease

Clinical type 2 diabetes

Structural changes†

Rising blood pressure

Rising serum creatinine levels

Cardiovascular death

Microalbuminuria

2 5 10 20Years

* Renal hemodynamics altered, glomerular hyperfiltration.† Glomerular basement membrane thickening ↑, mesangial expansion ↑, microvascular changes +/-.

Philippine NNHeS 2003-2004 Renal ReportMicroalbuminuria

This is equivalent to 8,626,027 Filipinos

Prevalence of microalbuminuria was 18.5%

Philippine NNHeS 2003-2004 Renal ReportMacroalbuminuria

At least +1 proteinuria using the Multiple Reagent Strip for Urinalysis® (Bayer Corporation)

Prevalence of macroalbuminuria was 4.2%

How Protein Spills into the Urine

diabetic kidney walls of the glomerulus allow proteins to escape

frothy urine

Primary Renal Disease among Filipino Patients on Dialysis (Chronic Kidney Disease)

0

1000

2000

3000

40002005 2006 2007 2008

Glomerulonephritis Diabetic Kidney Disease

Hypertensive Nephrosclerosis

Philippine Renal Disease Registry 2006 -2009 reports

Increasing Prevalence of Chronic Kidney Disease (CKD)

Increasing prevalence expected

Aging population

Global epidemic of type 2 diabetes 1

Patients with stage 1-4 CKD outnumber patients with stage 5 CKD by ~50:1 in the US 2 1. El Nahas & Bello. Lancet. 2005;365:331-340

2. Coresh et al. Am J Kidney Dis. 2003;41:1-12

>1 million patients with CKD on dialysis worldwide

Approximately 250 000 new patients diagnosed with CKD each year 3

3. Moeller et al. Nephrol Dial Transplant. 2002;17:2071-2076

Increasing Prevalence of Chronic Kidney Disease (CKD)

Stages in Progression of CKD

CKDdeath

Complications

Normal Increasedrisk

Kidneyfailure

Damage ↓ GFR

Screening for CKD risk factors, i.e. diabetes

CKD risk reduction; Screening for CKD

Diagnosis & treatment; Treat comorbid conditions; Slow progression

Estimate progression; Treat complications; Prepare for replacement

Replacement by dialysis and transplant

Five Stages of Kidney Disease

1 2 3 4 5

Hyper-filtration

↑ kidney size

Micro-albuminuria

Macro-albuminuria

↑ BUN, Crea, BP

↑↑ urine protein

↑↑ BUN, Crea, BP

End stage renal

disease

GFR >90 ml/min

GFR 60-89 ml/min

GFR 30-59 ml/min

GFR 15-29 ml/min

GFR <15 ml/min

National Statistics Office

Kidney disease is now the #10

cause of mortality in the

Philippines

Delaying Progression of DKD to CKD

AACE-

inhibitors/ ARBs

BBlood

Pressure

DDiet

EEducate

FFasting

blood sugar

CCholesterol

GGlass of

water

HHemoglobin

AACE-

inhibitors/ ARBs

ACE inhibitors: captopril, enalapril, lisinopril, perindopril etc.

Angiotensin II Receptor Blockers (ARBs): losartan, irbesartan, olmesartan, telmisartan, reytan etc.

Very good antihypertensives, especially in combination with other drugs

For kidney protection: reduces protein spillage in the urine

Benefits of ACE Inhibitors

Reduces risk of heart attack and stroke

Works well with other antihypertensive medications like calcium channel blockers (i.e. amlodipine) and diuretics (thiazides)

Common side effects: cough, angioedema

Target BP for diabetics <130/80 mm Hg

Target BP for diabetics with kidney disease <125/75 mm Hg

BBlood

Pressure

The closer to normal BP levels are, the better!Ischemic heart disease rates by SBP, DBP and age

Systolic Blood Pressure

40-49 years

50-59 years

60-69 years

70-79 years

80-89 years

Age at risk:

IHD mortality(floating absolute risk and 95% CI)

256

128

64

32

16

8

4

2

1

120 140 160 180

Usual SBP (mm Hg)

Diastolic Blood Pressure

256

128

64

32

16

8

4

2

1

70 80 90 100 110

Usual DBP (mm Hg)

Age at risk:

40-49 years

50-59 years

60-69 years

70-79 years

80-89 years

CI, confidence interval; IHD, ischemic heart disease. Lewington S et al. Lancet. 2002;360(9349):1903-1913.

Total cholesterol <200 mg/dL

LDL <100 mg/dL

Triglycerides <150 mg/dL

HDL: ♂>40 mg/dL ♀>50 mg/dL

CCholesterol

Association between Risk Factors and a Heart Attack

INTERHEART, 2004

Dyslipidemia

Smoking

Diabetes

Hypertension

Abdominal obesity

More vegetables and fruits

Exercise

Moderate alcohol intake

Relationship Between Changes in LDL-C and HDL-C and Coronary Heart Disease (CHD)

1% increase in HDL-C reduces CHD risk by 3%

Good cholesterol

Bad cholesterol

1% decrease in LDL-C reduces CHD risk by 1%

Low protein diet and very low protein diet

Low salt, low fat diet

DDiet

Protein Intake and Restriction in Diabetes

High protein intake increases risk of diabetic kidney disease and progression to end-stage renal disease

Diabetic patients who had lower protein intake had lower prevalence of microalbuminuria

Protein Intake and Restriction in Diabetes

Protein restriction reduces the workload of the kidney

0.6 to 0.7 g/kg protein intake reduces the rate of fall of GFR modestly

Recommended Dietary Protein Intake

Protein intake based on ideal body weight

Minimum daily protein requirement World Health Organization 0.45 g protein per kilogram

Maximum daily protein requirement US RDA and UK Department of Health & Social Security 0.8 g protein per kilogram

Low Protein Diet

Conventional low protein diet (LPD)

0.6 g protein/kg/day

50-60% must be of high biologic value

Low Protein Diet

Very low protein diet (VLPD)

1/2 LPD

Does not provide the daily requirements for essential amino acids

Supplementation is necessary

(Very) Low Protein Diet: A Mainly Vegetarian Diet

Food Not Allowed in Large Amounts

Meat, fish, eggs, milk and milk products, cheese, shellfish, roe

Protein intake in a 60 kg person/day0.45-0.8 grams/kg= 27 to 48 g

Serving size: 1 sandwich

Energy 540 cal

Total fat 30 g Total carbohydrate 47 g Protein 25 g

Specific manufactured foods totally lacking in protein

Bread

Wafers

Biscuits

Noodles

Flour

Educate and Empower

Healthy lifestyle

Smoking cessation

Weight reduction and exercise

Regular follow-up with your doctor

Early referral to a nephrologist

EEducate

Strict control of FBS & HbA1c

Dietary restrictions

Oral hypoglycemic agents

Insulin

FFasting

blood sugar

Eight glasses of water

Essential to hydrate well

What goes in must go out (>2 liters urine/day)

Essential to prevent kidney stone formation

Diet colas?

GGlass of

water

Typical Daily Water Balance in a Normal Human

SourceWater intake, ml/day

SourceWater output, ml/

day

Obligatory Elective Obligatory Elective

Ingested water 400 1000 Urine 500 1000

Water content of food

850 Skin 500

Water of oxidation

350 Respiratory tract

400

Stool 200

Total 1600 1000 Total 1600 1000

Anemia is an early sign of chronic kidney disease (reduced erythropoetin)

Risk of anemia is increased 2-3x in people with diabetes

HHemoglobin

Stages of CKD

ESRDCKD CARE

Stage 5Stage 4Stage 3Stage 2Stage 1

eGFR (mL/min/1.73m2)

>90(& kidney damage)

60-89 30-59 15-29 <15(or dialysis)

Drüeke F. WCN, Singapore, 2005

End Stage Renal Disease

sMDRD formula: 186 x serum creatinine-1.154 x age-0.202 x (1.212 if black) x (0.742 if female)

Awareness of Anemia in Patients with Diabetes

60%14%

26%Aware they were at

risk for anemia

Aware that they had been diagnosed with anemia

504 respondents selected from a nationally representative panel of people with diabetes

Awareness of anemia in MDs taking care of diabetics

77%

23%Unrecognized anemia by WHO definition (n=190)

820 patients in a diabetes clinic

Anemia - Definitions

WHO definition

Hb < 13 g/dL (male & post-menopausal females)

Hb < 12 g/dL (pre-menopausal females)

K-DOQI

Hb < 13.5 g/dL in adult males

Hb < 12 g/dL in adult females

Expected Benefits of Anemia Management in CKD

Better quality of life

Decrease in morbidity

Decrease in risk for heart attack and stroke

Decrease in the size of a failing heart

Lower hospitalization rates

Slower progression to kidney failure and dialysis

Increased survival and better quality of life

Reversal of anemia by epoetin can retard progression of chronic renal failure

Adapted from Kuriyama et al Nephron 1997; 77: 176-185

Cum

ulat

ive

rena

l sur

viva

l rat

e (%

)

20

0

40

60

80

100

0 5 10 15 20 25 30 35 40

p=0.

0024

p=0

.311

1

p=0.

0003

Months of follow-up

Hct <30%, treated with epoetinHct >30%, untreatedHct <30%, untreated

n=108

Check your urine

Frothy urine vs clear light yellow urine

frequency , dribbling, difficulty in urination, painful urination

Proteinuria

WBCs and RBCs

UUrine

Check your urine

Urinalysis

In the absence of UTI

First void

Midcatch stream

Request for a MICRAL test if routine urinalysis is negative

Chronic Kidney Disease and Diabetes

In most patients with diabetes, CKD should be attributable to diabetes if:

Macroalbuminuria is present; or

Microalbuminuria is present

In the presence of diabetic retinopathy

NKF K/DOQI Clinical Practice Guidelines and Clinical Practice Recommendations for Diabetes and Chronic Kidney Disease, AJKD, Vol 49, No 2, Supplement 2, February 2007

Delaying Progression of DKD to CKD

Delaying Progression of DKD to CKD

AACE-

inhibitors/ ARBs

Delaying Progression of DKD to CKD

AACE-

inhibitors/ ARBs

BBlood

Pressure

Delaying Progression of DKD to CKD

AACE-

inhibitors/ ARBs

BBlood

Pressure

CCholesterol

Delaying Progression of DKD to CKD

AACE-

inhibitors/ ARBs

BBlood

Pressure

DDiet

CCholesterol

Delaying Progression of DKD to CKD

AACE-

inhibitors/ ARBs

BBlood

Pressure

DDiet

EEducate

CCholesterol

Delaying Progression of DKD to CKD

AACE-

inhibitors/ ARBs

BBlood

Pressure

DDiet

EEducate

FFasting

blood sugar

CCholesterol

Delaying Progression of DKD to CKD

AACE-

inhibitors/ ARBs

BBlood

Pressure

DDiet

EEducate

FFasting

blood sugar

CCholesterol

GGlass of

water

Delaying Progression of DKD to CKD

AACE-

inhibitors/ ARBs

BBlood

Pressure

DDiet

EEducate

FFasting

blood sugar

CCholesterol

GGlass of

water

HHemoglobin

Delaying Progression of DKD to CKD

AACE-

inhibitors/ ARBs

BBlood

Pressure

DDiet

EEducate

FFasting

blood sugar

CCholesterol

GGlass of

water

HHemoglobin

UUrine

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