A Comprehensive Approach to Kidney Disease and Hypertension

PAWANG HAZWANUnit Ginjal dan Hipertensi

Ilmu Penyakit Dalam

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

Apa penyebab Gagal Ginjal ?

Gagal Ginjal

Akut

Kronik

• Chronic– CKD: Chronic Kidney

Disease• Acute

– ARF: Acute Renal Failure– AKI: Acute Kidney Injury

• Acute Classification– Pre-renal– Renal– Post-renal

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

Diseases of the Kidney

All global renal diseases affect glomerular

filtration rate (GFR)

• Diabetes• Hypertension• Atherosclerosis• Glomerular diseases• Toxins

– Gentamicin– NSAIDS– Compound analgesics

• Inherited diseases• Tubular disorders

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.

http://www.kidney.org/professionals/kdoqi/guidelines_ckd/Gif_File/kck_t10.gif

• 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

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

J Winterbottom 2005

Sign n SymptomsUraemia symptoms;Bad breath (urinous,ammonia)

Oedema (eyes, face, arms,hands, feet)

HypertensionExtended neck veinsFatigue (anaemia,toxic substances)

Neurological disturbances (lethargy, confusion,sleep disorders)

J Winterbottom 2005

Sign n Symptoms

Nausea & vomitingHeadachesPruritus (phosphate, calcium, aluminium)

BreathlessnessBone & joint problems (calcium/phosphate

imbalances,VitD deficiency,demineralization)Bone pain

J Winterbottom 2005

Investigation

HbUrea n electrolyteCreatinineAlk phosphatasePTHUrineimaging

Bagaimana dengan Anemia Renal ?

Anemia Rates Increase as Levels of CKD Severity Progress

20

8

17

43

8

15

62

15

10

14

95

0

20

40

60

80

100

<2 2-2.9 3-3.9 ≥4

Creatinine (mg/dL)

Anemia Prevalence (%

)

Hgb Values

11-12 g/dL10-11 g/dL<10 g/dL

Hgb = hemoglobin.Kausz et al. Dis Manage Health Outcomes. 2002;10:505-513.

Chronic Kidney Disease (CKD) Progression

Gagal GinjalNormal

Chronic kidney disease (CKD) Anemia is an expected complication of CKD

Increased cardiovascular morbidity

Left Ventricular Hypertrophy (LVH)

Congestive Heart Failure (CHF)

Treatment

recombinant human erythropoietin (r-HuEPO)

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

Why are CKD/ESRD Patients Predisposed to CV Disease?

INFLAMMATION plus CaP deposition

CV DISEASE AND DEATH

CKD/ESRD

ANEMIA LVH/CHFLIPIDS HTN

CAD and PVD

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.

Bagaimana hubungan antara hipertensi dengan CKD ?

Distribution of hypertensives (65-89 years)

MEN

59.3%

30.3%

10.4%

WOMEN

63.6%

8.7%

27.7%

ISOLATED SYSTOLIC

ISOLATED DIASTOLIC

COMBINED

ISOLATED SYSTOLIC

ISOLATED DIASTOLIC

COMBINED

Framingham study

Factors Affecting Blood Pressure

Blood Pressure

Cardiac Output

Total Peripheral Resistance

= XAmount of blood

ejected per minute Blood flow through blood vessels

Prevalence of HTN in CKD

80% of patients with glomerulonephritis and 30% of patients with chronic interstitial disease are hypertensive.

Aggressive BP Control, Proteinuria and CKD Progression – what is the optimal BP

for CKD?

-12

-10

-8

-6

-4

-2

0<1 gm/D 1-2.9

gm/D>3 gm/D

Mean fall in GFR

(ml/min/yr)

<125/75<140/90

Klahr S et al, N Engl J Med 330:877, 1994

**

GOAL BP<125/75 if >1 gm proteinuria

GFRProteinuriaAldosterone releaseGlomerular sclerosis

A II

Atherosclerosis*VasoconstrictionVascular hypertrophyEndothelial dysfunction

LV hypertrophyFibrosisRemodelingApoptosis

Stroke

Death

*Preclinical data.LV = left ventricular; MI = myocardial infarction; GFR = glomerular filtration rate.

Hypertension

Heart FailureMI

Renal Failure

Angiotensin II plays a central role in organ damage

Renin Angiotensin Aldosterone System

Angiotensinogen

Non-ACE pathways(eg, chymase)

Vasoconstriction Cell growth Na/H2O retention Sympathetic activation

Renin Angiotensin I

Angiotensin II

ACE

Cough,angioedema

Benefits? Bradykinin

Inactivefragments

Vasodilation Antiproliferation

(kinins)

Aldosterone AT2

AT1

Decreasedvasodilatoryprostaglandins

Increasedangiotensin II

Low GFR

How About Renal Osteodystrophy

Bone Disease in CKD

Metabolic abnormalities Hyperphosphatemia Hypocalcemia PTH elevation

Bone Disease in CKD Renal Osteodystrophy

Osteomalacia / osteitis fibrosis cystica / osteosclerosis

Metastatic calcification Vascular!

Bone Disease in CKD Renal Osteodystrophy

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