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
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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....
