KIDNEY DISEASES

Ivan Surya Pradipta

DEPARTMENT OF PHARMACOLOGY & CLINICAL PHARMACY FACULTY OF PHARMACY UNIVERSITAS PADJADJARAN BANDUNG

KIDNEY FUNCTION
Excretion of metabolic waste product Regulate fluid and electrolyte balance Regulate acid-base balance Secretion, excretion, and metabolism of hormone Forming erythrocytes Gluconeogenesis

REABSORBPTION DAN EXCRETION FUNCTION

FORMING ERYTHROCYTES FUNCTION

KIDNEY ERYTHROPOETIN PRO-ERYTHROBLAST

ERYTHROCYTES

Fe & Vitamins

BLOOD PRESSURE REGULATION

P. ARTERIAL P. Hydrostatic GFR NaCl on JUKSTAGLOMERULUS

RENIN RELEASED ANGIOTENSIN I

ANGIOTENSIN II
VASOCONTRICTION NACL & WATER RETENTION

ELEVATED BLOOD PRESSURE

Definition CKD
Kidney damage for > 3 month as define by :
Structural or functional abnormality of the kidney With or without decreased GFR Manifested by either pathologic abnormalities Or markers of kidney damage (abnormalities in the composition of blood or urine) Or abnormalities in imaging test.

Chronic vs. Acute Renal Failure

Acute Renal Failure (ARF): a. Abrupt onset b. Potentially reversible Chronic Renal Failure (CRF): a. Progresses over at least 3 months b. Permanent- non-reversible damage to nephrons

Epidemiology
In US 1995-1999 : 100 case ckd / million population every years increased approximately 8 % /years In Malaysia, 1800 new case ckd /18 million population/years In development country : 40-60 case / million/years

Etiology
Diabetes (40% of new cases of ESRD) Hypertension ( 25 % of new cases) Glomerulonephritis (10%) Others: Urinary tract disease
Polycystic kidney disease SLE Exposure chemical properties Chronic inflamation Obstruction Vascular disease (renal artery disease, hypertension) Transplant unknown
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Risk Factors For Kidney Disease

Susceptibility: Advanced age (>60 years), Race (African-American, Hispanic, American India, Asian), dyslipidemia, systemic inflammation, reduced kidney mass, Family history Initiation: DM, HTN, autoimmune diseases, drug toxicity, exposure heavy metals Progression: Hyperglycemia, elevated blood pressure, proteinuria, smoking.
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Incident Counts & Adjusted Rates, By Primary Diagnosis in England

USRDS, 2004

PROGNOSIS
NORMAL
INCREASED RISK DAMAGE LOW GFR

COMPLICATIONS

CKD DEATH

RENAL FAILURE

Pathophysiology of CRF
Progressive destruction of nephrons leads to: a. Decreased glomerular filtration, tubular reabsorption & renal hormone regulation b. Functional and structural changes occur c. Inflammatory response triggered d. Healthy glomeruli so overburdened they become stiff, sclerotic and necrotic

Lippincott Williams & Wilkins (2005). Pathophysiology A 2-1 reference for nurses (1st ed.) Ambler, Pa.:Lippincott Williams & Wilkins

Structural Changes of CRF

Epithelial damage Glomerular and parietal basement membrane damage Vessel wall thickening Vessel lumen narrowing leading to stenosis of arteries and capillaries Sclerosis of membranes, glomeruli and tubules Reduced glomerular filtration rate Nephron destruction
Valerie Kolmer 2006

Healthy Glomerulus

Damaged Glomerulus

Functional Changes of CRF

The Kidneys are unable to: Regulate fluids and electrolytes Balance fluid volume and renin-angiotensin system Control blood pressure Eliminate nitrogen and other wastes Synthesize erythropoietin Regulate serum phosphate and calcium levels

Stages of CKD
Stage
1

Description

GFR ml/min/1.73m
> 90.0

Kidney damage with normal or GFR

Kidney damage with mild GFR

2
3 4 5

60-89

Moderate GFR
Severe GFR

30-59

15-29

Kidney failure ( ESRD)

<15 ( or dialysis)

osteodistrofi

SIGNS & SYMPTOMS Lab Value Cues

1. Anemias - decreased erythropoietin secretion & uremic toxin damage to RBCs Azotemia (elevated nitrogen) retention of nitrogenous wastes Creatinine a component of muscle & its non-protein waste product. Normally filtered in the glomerulus & lost in the urine. Glomerular damage increases reabsorption into the blood. Serum creatinine 3 x normal shows a 75% loss of renal function.
http://office.microsoft.com/en-us/tou.aspx

2.

3.

SIGNS & SYMPTOMS Lab Value Cues

4.

5.

Hypocalcemia impaired regulation of Vitamin D leads to decreased absorption & low calcium levels. Hyperkalemia impaired excretion of potassium by the kidneys leads to elevated potassium levels.

6.

7.

Hyperlipidemia decreased serum albumin leads to increased synthesis of LDLs & cholesterol by the liver, contributing to elevated lipid levels Proteinuria increased protein filtration glomeruli damage

http://office.microsoft.com/en-us/tou.aspx

SIGNS & SYMPTOMS Visual / Verbal Cues

1) Fatigue, nausea uremia 2) Hypertension sodium & water retention 3) Hypervolemia sodium & water retention 4) Gray/yellow skin accumulated urine pigments

5) Cardiac irritability hyperkalemia 6) Muscle cramps hypocalcemia 7) Bone & muscle pain hypocalcemia / hyperphosphatemia

http://office.microsoft.com/en-us/tou.aspx

Metabolic Impact
Hyperlipidemia common in CRFespecially in Nephrotic Syndrome Excessive lipids accelerate progression of renal disease Cholesterol increases glomerular injury

Contributing Mechanisms
Two known paths of hyperlipidemia progression in CRF: Hyperlipidemia activates LDL receptors in mesangial cells increased lipid deposit increased glomeluro injury

Increased synthesis of lipoproteins in the liver related to increased albumin production

Albumin Contribution
Progression of glomeruli injury leads to increased capillary filtration of albumin The liver compensates and increases albumin production - to replace albumin lost in urine

This leads to increased synthesis of lipoproteins by the liver secondary to the compensatory increase in albumin production. Results in increased LDL levels predisposing to atherosclerosis
Atherosclerosis further increases glomeruli injury

CHRONIC RENAL FAILURE: CLINICAL MANIFESTATIONS

Sodium and water retention Hyperkalemia Metabolic Acidosis Mineral and Bone metabolism Cardiovascular and Pulmonary Disorders Hematologic Abnormalities Neuromuscular Abnormalities Endocrine Abnormalities Dermatologic Abnormalities Dyslipidemia

Early Treatment Makes a Difference

Brenner, et al., 2001

How pharmacist contributed ?

EARLY STAGES OF CKD

Pharmacists can help in patient assessment to determine the adequacy of drug therapy regimens to achieve treatment goals and modifications as required assessment of drug therapy selections based on medical indications, selection of specific drug dosages Drug dosing adjustments Monitoring for efficacy and toxicity. Minimizing exposure to nephrotoxic agents, especially drugs.
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SAVE YOUR KIDNEYS....