Lecture at the Guam Diabetes Association meeting (8 November 2009) for patients with diabetes

1. PROTECTING THE
KIDNEY IN DIABETES
Rey Jaime M. Tan MD, FPCP
Clinical Associate Professor
University of the Philippines College of Medicine
Section of Nephrology, Department of Medicine
UP-Philippine General Hospital

2. 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?

3. The kidney

4. The kidney
Filters the blood

5. The kidney
Filters the blood
Reabsorbs all
necessary nutrients in
the blood

6. The kidney
Filters the blood
Reabsorbs all
necessary nutrients in
the blood
Excretes all waste
products in the urine

7. The kidney

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

9. The kidney
Involved in synthesis
of hormones i.e.
vitamin D,
erythropoietin etc.
Maintains balance in
electrolytes, acids and
bases

10. The nephron
Functional unit of
the kidney
1,000,000
nephrons per
kidney

11. Diabetic Kidney Disease
A Complication of Diabetes
Leading cause of
blindness in adults 2 to 4-fold
24000 new cases increase in stroke
each year in US
Diabetic Stroke
Leading cause of Retinopathy
end-stage renal
disease in adults
44% new cases/yr
Diabetic
Nephropathy Cardiovascular
Disease
Leading cause of
non-traumatic 8 out of 10 diabetic
limb amputations patients die from
60% new cases/ cardiovascular events
yr Diabetic 5-10 year reduction
Neuropathy in life expectancy
NIDDK, National Diabetes Statistics fact sheet. HHS, NIH, 2006.

12. Natural History of Type 2
Diabetic Kidney Disease
Clinical type 2 diabetes
Functional changes*
Structural changes†
Rising blood pressure
Microalbuminuria
Proteinuria
Rising serum
creatinine levels
End-stage
renal disease
Cardiovascular death
Onset of
2 5 10 20
diabetes Years
* Renal hemodynamics altered, glomerular hyperfiltration.
† Glomerular basement membrane thickening ↑, mesangial expansion ↑, microvascular changes +/-.

13. Philippine NNHeS 2003-2004 Renal Report
Microalbuminuria
This is equivalent to
8,626,027 Filipinos
Prevalence of
microalbuminuria
was 18.5%

14. Philippine NNHeS 2003-2004 Renal Report
Macroalbuminuria
At least +1 proteinuria
using the Multiple
Reagent Strip for
Urinalysis® (Bayer
Corporation)
Prevalence of
macroalbuminuria
was 4.2%

15. How Protein Spills into the Urine
diabetic kidney
walls of the
glomerulus allow
proteins to escape
frothy urine

16. Primary Renal Disease among Filipino Patients
on Dialysis (Chronic Kidney Disease)
2005 2006 2007 2008
4000
3000
2000
1000
0
Glomerulonephritis Diabetic Hypertensive
Kidney Disease Nephrosclerosis
Philippine Renal Disease Registry 2006 -2009 reports

17. 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

18. Increasing Prevalence of
Chronic Kidney Disease (CKD)
>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

19. Stages in Progression of CKD
Complications
Increased ↓ GFR Kidney CKD
Normal Damage
risk failure death
Screening CKD risk Diagnosis & Estimate Replacement
for CKD risk reduction; treatment; progression; by dialysis and
factors, i.e. Screening Treat comorbid Treat transplant
diabetes for CKD conditions; Slow complications;
progression Prepare for
replacement

20. Five Stages of Kidney Disease
1 2 3 4 5
Macro- ↑↑ urine
Hyper- End stage
Micro- albuminuria protein
filtration renal
albuminuria ↑ BUN, Crea, ↑↑ BUN,
↑ kidney size disease
BP Crea, BP
GFR >90 GFR 60-89 GFR 30-59 GFR 15-29 GFR <15
ml/min ml/min ml/min ml/min ml/min

21. National Statistics Office
Kidney disease is
now the #10
cause of
mortality in the
Philippines

22. Delaying Progression
of DKD to CKD
A B C D
ACE- Blood Cholesterol Diet
inhibitors/ Pressure
ARBs
E F G H
Educate Fasting Glass of Hemoglobin
blood sugar water

23. A
ACE-
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

24. 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

25. B
Blood
Pressure
Target BP for diabetics
<130/80 mm Hg
Target BP for diabetics
with kidney disease
<125/75 mm Hg

26. The closer to normal BP levels are, the better!
Ischemic heart disease rates by SBP, DBP and age
Systolic Blood Age at risk: Diastolic Blood Age at risk:
256 Pressure Pressure
80-89 years 256
80-89 years
128 128
70-79 years 70-79 years
64 64
60-69 years 60-69 years
IHD 32 32
mortality 50-59 years 50-59 years
16 16
(floating 40-49 years 40-49 years
absolute 8 8
risk and 4
4
95% CI)
2 2
1 1
120 140 160 180 70 80 90 100 110
Usual SBP (mm Hg) Usual DBP (mm Hg)
CI, confidence interval; IHD, ischemic heart disease.
Lewington S et al. Lancet. 2002;360(9349):1903-1913.

27. C
Cholesterol
Total cholesterol <200 mg/dL
LDL <100 mg/dL
Triglycerides <150 mg/dL
HDL: >40 mg/dL >50 mg/dL

28. Association between Risk
Factors and a Heart Attack
INTERHEART, 2004
More
Dyslipidemia vegetables
and fruits
Smoking
Exercise
Diabetes
Moderate
Hypertension
alcohol intake
Abdominal
obesity

29. Relationship Between Changes in LDL-C and
HDL-C and Coronary Heart Disease (CHD)
Bad
cholesterol
Good
cholesterol 1% decrease
in LDL-C
1% increase
reduces CHD
in HDL-C
risk by 1%
reduces CHD
risk by 3%

30. D
Diet
Low protein diet and very low protein diet
Low salt, low fat diet

31. 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

32. 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

33. 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

34. Low Protein Diet
Conventional low protein diet (LPD)
0.6 g protein/kg/day
50-60% must be of high biologic value

35. Low Protein Diet
Very low protein diet (VLPD)
1/2 LPD
Does not provide the daily requirements for
essential amino acids
Supplementation is necessary

36. (Very) Low Protein Diet:
A Mainly Vegetarian Diet

37. Food Not Allowed
in Large Amounts
Meat, fish, eggs, milk and milk
products, cheese, shellfish, roe

38. Protein intake in a 60 kg person/day
0.45-0.8 grams/kg
= 27 to 48 g
Serving size:
1 sandwich
Energy 540 cal
Total fat 30 g
Total carbohydrate 47 g
Protein 25 g

39. Specific manufactured foods
totally lacking in protein
Bread
Wafers
Biscuits
Noodles
Flour

40. E Educate and Empower
Educate
Healthy lifestyle
Smoking cessation
Weight reduction and exercise
Regular follow-up with your doctor
Early referral to a nephrologist

41. F Strict control of
Fasting
FBS & HbA1c
blood sugar
Dietary restrictions
Oral hypoglycemic agents
Insulin

42. G
Glass of
water
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?

43. Typical Daily Water Balance
in a Normal Human
Water intake, ml/day Water output, ml/
Source Source day
Obligatory Elective Obligatory Elective
Ingested water 400 1000 Urine 500 1000
Water content 850 Skin 500
of food
Water of 350 Respiratory 400
oxidation tract
Stool 200
Total 1600 1000 Total 1600 1000

44. H
Hemoglobin
Anemia is an
early sign of
chronic kidney disease
(reduced erythropoetin)
Risk of anemia is
increased 2-3x in
people with diabetes

45. Stages of CKD
CKD CARE ESRD
End Stage Renal Disease
Stage 1 Stage 2 Stage 3 Stage 4 Stage 5
>90 60-89 30-59 15-29 <15
(& kidney (or dialysis)
damage) eGFR (mL/min/1.73m2)
sMDRD formula:
186 x serum creatinine-1.154 x age-0.202 x (1.212 if black) x (0.742 if female)
Drüeke F. WCN, Singapore, 2005

46. Awareness of Anemia in
Patients with Diabetes
Aware they were at
26% risk for anemia
60%
14% Aware that they had been
diagnosed with anemia
504 respondents selected from a nationally
representative panel of people with diabetes

47. Awareness of anemia in MDs
taking care of diabetics
Unrecognized
23% anemia by WHO
definition (n=190)
77%
820 patients in a diabetes clinic

48. 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

49. 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

50. Reversal of anemia by epoetin can retard
progression of chronic renal failure
100 Hct <30%, treated with epoetin
Cumulative renal survival rate (%)
Hct >30%, untreated
Hct <30%, untreated
80
60
40
p=0.0024 p=0.3111
p=0.0003
20 n=108
0
0 5 10 15 20 25 30 35 40
Months of follow-up
Adapted from Kuriyama et al Nephron 1997; 77: 176-185

51. U Check your urine
Urine
Frothy urine vs clear light yellow urine
frequency , dribbling, difficulty in urination, painful
urination
Proteinuria
WBCs and RBCs

52. Check your urine
Urinalysis
In the absence of UTI
First void
Midcatch stream
Request for a MICRAL test if routine urinalysis is
negative

53. 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

54. Delaying Progression
of DKD to CKD

55. Delaying Progression
of DKD to CKD
A
ACE-
inhibitors/
ARBs

56. Delaying Progression
of DKD to CKD
A B
ACE- Blood
inhibitors/ Pressure
ARBs

57. Delaying Progression
of DKD to CKD
A B C
ACE- Blood Cholesterol
inhibitors/ Pressure
ARBs

58. Delaying Progression
of DKD to CKD
A B C D
ACE- Blood Cholesterol Diet
inhibitors/ Pressure
ARBs

59. Delaying Progression
of DKD to CKD
A B C D
ACE- Blood Cholesterol Diet
inhibitors/ Pressure
ARBs
E
Educate

60. Delaying Progression
of DKD to CKD
A B C D
ACE- Blood Cholesterol Diet
inhibitors/ Pressure
ARBs
E F
Educate Fasting
blood sugar

61. Delaying Progression
of DKD to CKD
A B C D
ACE- Blood Cholesterol Diet
inhibitors/ Pressure
ARBs
E F G
Educate Fasting Glass of
blood sugar water

62. Delaying Progression
of DKD to CKD
A B C D
ACE- Blood Cholesterol Diet
inhibitors/ Pressure
ARBs
E F G H
Educate Fasting Glass of Hemoglobin
blood sugar water

63. Delaying Progression U
of DKD to CKD Urine
A B C D
ACE- Blood Cholesterol Diet
inhibitors/ Pressure
ARBs
E F G H
Educate Fasting Glass of Hemoglobin
blood sugar water

64. Thank You
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