Slides of 1 of my colleague... Hazwan

1. A Comprehensive Approach to
Kidney Disease and Hypertension
PAWANG HAZWAN
Unit Ginjal dan Hipertensi
Ilmu Penyakit Dalam

2. Ginjal
Fungsi Ginjal
• Regulasi volume cairan
• Regulasi keseimbangan elektrolit
• Regulasi keseimbangan asam dan basa
• Regulasi tekanan darah (RAAS)
• Regulasi eritropoesis
• Ekskresi sampah metabolik
• Metabolisme vitamin D
• Sintesis prostaglandin

5. Apa penyebab Gagal Ginjal ?

6. Akut
Gagal Ginjal
Kronik

7. • Chronic
– CKD: Chronic Kidney Disease
• Acute
– ARF: Acute Renal Failure
– AKI: Acute Kidney Injury
• Acute Classification
– Pre-renal
– Renal
– Post-renal

9. The CKD problem
• Clinically silent in the early stages
• Cost of renal disease can be extreme to
health care service
• Effects of renal disease can be extreme on
patient
• Treatments now available to slow progression
• Need an “early warning” system for CKD

10. Diseases of the Kidney
• Diabetes
• Hypertension
• Atherosclerosis
• Glomerular diseases
All global renal diseases
• Toxins
– Gentamicin
affect glomerular
– NSAIDS filtration rate (GFR)
– Compound analgesics
• Inherited diseases
• Tubular disorders

11. Definition of CKD
• Kidney damage for 3 months
– Defined by structural or functional abnormalities of
the kidney,
with or without decreased glomerular filtration rate
(GFR)
• Reduced GFR for 3 months
• New staging for chronic kidney disease (CKD)
is primarily based on kidney function.
National Kidney Foundation (NKF). Am J Kidney Dis. 2002;39(2 suppl 1):S1-S266.

13. • Glomerular Filtration Rate is the volume of fluid passing
through the glomerulus in a given period of time.
• Influenced by renal perfusion pressure, renal vascular
resistance, glomerular damage, post-glomerular
resistance.
• “Normal Range” approx 90 - 150 mL/min
– Approx 170 L per day
• A larger healthy person has a higher GFR
– Can be reported as 90 - 150 mL/min/1.73m2
• Values fall with increasing age

14. Other reasons for estimating the GFR
• Monitoring progression of CKD
• GFR estimates are used for drug dosing
decisions
– Dosing of renally excreted drugs
– Avoiding nephrotoxic drugs
• Risk factor for cardiovascular disease
mortality
• Renal involvement in systemic diseases, such
as diabetes mellitus or SLE

15. Sign n Symptoms
Uraemia symptoms;
Bad breath (urinous,ammonia)
Oedema (eyes, face, arms,hands, feet)
Hypertension
Extended neck veins
Fatigue (anaemia,toxic substances)
Neurological disturbances
(lethargy, confusion,sleep disorders)
J Winterbottom 2005

16. Sign n Symptoms
Nausea & vomiting
Headaches
Pruritus (phosphate, calcium, aluminium)
Breathlessness
Bone & joint problems (calcium/phosphate
imbalances,VitD deficiency,demineralization)
Bone pain
J Winterbottom 2005

17. Investigation
Hb
Urea n electrolyte
Creatinine
Alk phosphatase
PTH
Urine
imaging
J Winterbottom 2005

18. Bagaimana dengan Anemia Renal ?

19. Anemia Rates Increase as Levels of CKD Severity
Progress
100
Hgb Values
Anemia Prevalence (%)
10
80
15 11-12 g/dL
60 15
10-11 g/dL
<10 g/dL
8
40 17
62
9 8 43
20 5
20
14
0
<2 2-2.9 3-3.9 ≥4
Creatinine (mg/dL)
Chronic Kidney Disease (CKD) Progression
Hgb = hemoglobin.
Kausz et al. Dis Manage Health Outcomes. 2002;10:505-513.

20. Normal Gagal Ginjal

25. Chronic kidney disease (CKD) Anemia is an expected complication of CKD
Treatment Increased cardiovascular morbidity
recombinant human erythropoietin
(r-HuEPO) Left Ventricular Hypertrophy
(LVH)
Congestive Heart Failure (CHF)

26. Diambil : Jerome Rossert dkk, Nephrol Dial Transplant (2002) 17: 359–362

28. Why are CKD/ESRD Patients
Predisposed to CV Disease?
CKD/ESRD
ANEMIA INFLAMMATION plus CaP deposition LVH/CHF
LIPIDS HTN
CAD and PVD
CV DISEASE AND DEATH

29. Why are CKD/ESRD Patients
Predisposed to CV Disease?
• 30-50% of ESRD patients have INFLAMMATION (increased
CRP, increased IL-6, decreased albumin)
– Increased CRP is a primary marker for inflammation predicting
cardiovascular disease in normal adults
– Increased CRP is the primary marker for increased cardiovascular
mortality on dialysis
• CKD/ESRD patients have metastatic calcification (coronary
arteries) because of secondary hyperparathyroidism and
elevated PO4 levels.

30. Bagaimana hubungan antara
hipertensi dengan CKD ?

31. Distribution of hypertensives (65-89 years)
MEN WOMEN
ISOLATED
ISOLATED
SYSTOLIC
SYSTOLIC
59.3% 63.6%
30.3% 27.7%
10.4% 8.7%
COMBINED
COMBINED
ISOLATED ISOLATED
DIASTOLIC DIASTOLIC
Framingham study

32. Factors Affecting Blood Pressure
Blood Cardiac Total
Pressure = Output X Peripheral
Resistance
Amount of blood
ejected per minute Blood flow through
blood vessels

35. Prevalence of HTN in CKD
80% of patients with
glomerulonephritis
and 30% of patients
with chronic interstitial
disease are
hypertensive.

38. Aggressive BP Control, Proteinuria and
CKD Progression – what is the optimal BP
for CKD?
0
<1 gm/D 1-2.9 >3 gm/D
-2 gm/D
-4
Mean fall
<125/75
in GFR -6
(ml/min/yr) * <140/90
-8 *
-10
Klahr S et al, N Engl J
-12
Med 330:877, 1994
GOAL BP<125/75 if >1 gm proteinuria

39. Angiotensin II plays a central role in organ damage
Atherosclerosis* Stroke
Vasoconstriction
Vascular hypertrophy
Endothelial dysfunction Hypertension
A II LV hypertrophy
Fibrosis
Remodeling Heart Failure Death
Apoptosis MI
GFR
Proteinuria Renal Failure
Aldosterone release
Glomerular sclerosis
*Preclinical data.
LV = left ventricular; MI = myocardial infarction; GFR = glomerular filtration rate.

40. Renin Angiotensin Aldosterone System
Non-ACE pathways Vasoconstriction
(eg, chymase) Cell growth
Na/H2O retention
Sympathetic activation
Angiotensinogen
Renin Angiotensin I AT1
Angiotensin II
ACE
Aldosterone AT2
Cough, Vasodilation
Inactive Antiproliferation
angioedema Bradykinin fragments (kinins)
Benefits?

41. Decreased Increased
vasodilatory angiotensin II
prostaglandins
Low GFR

42. How About Renal Osteodystrophy

43. Bone Disease in CKD
 Metabolic abnormalities
 Hyperphosphatemia
 Hypocalcemia
 PTH elevation

44. Bone Disease in CKD
 Renal Osteodystrophy
 Osteomalacia / osteitis fibrosis cystica / osteosclerosis
 Metastatic calcification
 Vascular!

45. Bone Disease in CKD
 Renal Osteodystrophy

47. Matur nuwun