Download - Protecting the Kidney in Diabetes
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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
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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?
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The kidney
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The kidney
Filters the blood
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The kidney
Filters the blood
Reabsorbs all necessary nutrients in the blood
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The kidney
Filters the blood
Reabsorbs all necessary nutrients in the blood
Excretes all waste products in the urine
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The kidney
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The kidney
Involved in synthesis of hormones i.e. vitamin D, erythropoietin etc.
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The kidney
Involved in synthesis of hormones i.e. vitamin D, erythropoietin etc.
Maintains balance in electrolytes, acids and bases
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The nephron
Functional unit of the kidney
1,000,000 nephrons per kidney
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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.
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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 +/-.
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Philippine NNHeS 2003-2004 Renal ReportMicroalbuminuria
This is equivalent to 8,626,027 Filipinos
Prevalence of microalbuminuria was 18.5%
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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%
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How Protein Spills into the Urine
diabetic kidney walls of the glomerulus allow proteins to escape
frothy urine
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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
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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
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>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)
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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
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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
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National Statistics Office
Kidney disease is now the #10
cause of mortality in the
Philippines
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Delaying Progression of DKD to CKD
AACE-
inhibitors/ ARBs
BBlood
Pressure
DDiet
EEducate
FFasting
blood sugar
CCholesterol
GGlass of
water
HHemoglobin
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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
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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
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Target BP for diabetics <130/80 mm Hg
Target BP for diabetics with kidney disease <125/75 mm Hg
BBlood
Pressure
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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.
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Total cholesterol <200 mg/dL
LDL <100 mg/dL
Triglycerides <150 mg/dL
HDL: ♂>40 mg/dL ♀>50 mg/dL
CCholesterol
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Association between Risk Factors and a Heart Attack
INTERHEART, 2004
Dyslipidemia
Smoking
Diabetes
Hypertension
Abdominal obesity
More vegetables and fruits
Exercise
Moderate alcohol intake
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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%
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Low protein diet and very low protein diet
Low salt, low fat diet
DDiet
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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
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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
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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
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Low Protein Diet
Conventional low protein diet (LPD)
0.6 g protein/kg/day
50-60% must be of high biologic value
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Low Protein Diet
Very low protein diet (VLPD)
1/2 LPD
Does not provide the daily requirements for essential amino acids
Supplementation is necessary
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(Very) Low Protein Diet: A Mainly Vegetarian Diet
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Food Not Allowed in Large Amounts
Meat, fish, eggs, milk and milk products, cheese, shellfish, roe
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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
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Specific manufactured foods totally lacking in protein
Bread
Wafers
Biscuits
Noodles
Flour
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Educate and Empower
Healthy lifestyle
Smoking cessation
Weight reduction and exercise
Regular follow-up with your doctor
Early referral to a nephrologist
EEducate
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Strict control of FBS & HbA1c
Dietary restrictions
Oral hypoglycemic agents
Insulin
FFasting
blood sugar
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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
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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
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Anemia is an early sign of chronic kidney disease (reduced erythropoetin)
Risk of anemia is increased 2-3x in people with diabetes
HHemoglobin
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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)
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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
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Awareness of anemia in MDs taking care of diabetics
77%
23%Unrecognized anemia by WHO definition (n=190)
820 patients in a diabetes clinic
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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
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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
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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
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Check your urine
Frothy urine vs clear light yellow urine
frequency , dribbling, difficulty in urination, painful urination
Proteinuria
WBCs and RBCs
UUrine
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Check your urine
Urinalysis
In the absence of UTI
First void
Midcatch stream
Request for a MICRAL test if routine urinalysis is negative
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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
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Delaying Progression of DKD to CKD
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Delaying Progression of DKD to CKD
AACE-
inhibitors/ ARBs
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Delaying Progression of DKD to CKD
AACE-
inhibitors/ ARBs
BBlood
Pressure
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Delaying Progression of DKD to CKD
AACE-
inhibitors/ ARBs
BBlood
Pressure
CCholesterol
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Delaying Progression of DKD to CKD
AACE-
inhibitors/ ARBs
BBlood
Pressure
DDiet
CCholesterol
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Delaying Progression of DKD to CKD
AACE-
inhibitors/ ARBs
BBlood
Pressure
DDiet
EEducate
CCholesterol
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Delaying Progression of DKD to CKD
AACE-
inhibitors/ ARBs
BBlood
Pressure
DDiet
EEducate
FFasting
blood sugar
CCholesterol
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Delaying Progression of DKD to CKD
AACE-
inhibitors/ ARBs
BBlood
Pressure
DDiet
EEducate
FFasting
blood sugar
CCholesterol
GGlass of
water
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Delaying Progression of DKD to CKD
AACE-
inhibitors/ ARBs
BBlood
Pressure
DDiet
EEducate
FFasting
blood sugar
CCholesterol
GGlass of
water
HHemoglobin
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Delaying Progression of DKD to CKD
AACE-
inhibitors/ ARBs
BBlood
Pressure
DDiet
EEducate
FFasting
blood sugar
CCholesterol
GGlass of
water
HHemoglobin
UUrine