Transcript In the name of God Chronic Renal Failure

In the name of God
Chronic Renal Failure
By:
Dr. Shahram Ala
(PharmD, BCPS)
Kidney
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Each kidney has about 1 million nephrons
Receives 25% 0f GFR (1200 ml/min, > 1700 lit/d)
 1-1.5 lit urine (waste products & excess water)
 Reabsorption of sodium, glucose, water
 Secretion of urea, Cr, K+, H+, phosphate
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Other functions of kidneys
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Renin secretion
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Erythropoietin secretion
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Activation of vit D3 (Calcitriol)
Renal Failure
up to 75% of function can be lost before it is
noticeable
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ARF: Rapid onset,
usually reversible,
rapid reduction in
urine volume
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CRF: Slow onset,
progressive, is not
reversible
Treatment Modalities
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Hemodialysis
Peritoneal Dialysis
Renal Transplant
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In 1950s, Life expectancy of ESRD patients was just
a few days to weeks
Classification
Worldwide ESRD
CRF & ESRD
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CRF and ESRD are significant causes of
morbidity & mortality
Analgesic Nephropathy
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Tubulointerstitial renal disease (Papillary necrosis and
interstitial nephritis) due to ingestion of a mixture of 2
analgesics usually with codeine or caffeine
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More prevalent in females (5-7.1 times) with peak
incidence between 4th and 5th decade
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Salt-wasting nephropathy, ↓urine concentrating &
acidifying capacity
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Symptoms: flank pain, pyuria, hematuria, urethral
obstruction
Analgesic Nephropathy (cont.)
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Mechanism: oxidative metabolite of
acetaminophen beside reduced glutathione
capacity (due to ASA)
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Management: abstinence from NSAIDs &
combination analgesics, high fluid intake (if
possible), management of ESRD is similar to
other causes
Medication Use
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Both HD & PD patients receive a median of 8
different drugs including:
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Antihypertensives (CCBs, ACEIs)
Antidiabetic agents
Erythropoietin
Phosphate-binding agents
Multivitamins
Vit D supplements
ASA
Analgesics
GI agents
Warfarin
Nonadherence & drug-related problems
General feature in CRF
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Most patients are symptom free until renal
function is <25% normal
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At renal function <10% normal, uremic
symptoms occurs
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At renal function<5%, dialysis or transplant is
required
 Intact
nephron hypothesis
Pathogenesis
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Glomerular capillary hypertension
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Microalbuminuria or proteinuria
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Increased renal plasma flow (with high Pr Intake)
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Dyslipoproteinemia (esp. TG-rich apo-Blipoproteins)
Clinical assessment
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Evaluation of renal function
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BUN, SrCr
Clcr= (140-Age)BW/72*SrCr (*%85 for Females)
Clcr based on urine collection and measurement of UCr
Due to TS of creatinine in renal dysfunction, Clcr overestimates the
GFR
Proteinuria (Alb, Alb/Cr Ratio)
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Microalbuminuria: 30-300 mg/24h
Overt proteinuria: >300 mg/24h
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Dipstick test (Reagent strips)
Alb/Cr : 30-300 µg/mg (Microalbuminuria)
Prevention
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Antihypertensives
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Dietary Protein Restriction
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Treatment of Dyslipoproteinemia
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Intensive Glu Control (in Diabetic patients)
HTN & CRF
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HTN is both a cause and a result of RF
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HTN causes glumerolar hyperperfusion leading to
progressive renal damage
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Goal of BP:
130/85 (in patients with some degree of renal failure)
 125/75 (in patients with proteinuria >1gr)
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Prevention:
Which Antihypertensives?
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ACEIs (Enalapril, Captopril, Lisinopril)
 Ag II play a central role in glomerular capillary
pressure
ARAs (Losartan, Irbesartan, Valsartan, Candesartan,
Eprosartan, Telmisartan)
CCBs (Diltiazem, Verapamil are superior to Nifedipine)
 Effects
on renal hemodynamic, cytoprotective
& antiproliferative properties
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ACEIs+CCBs
Prevention:
Dietary Protein Restriction
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There is an association between “Protein ingestion”
&“GFR” and “Renal Plasma Flow”
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For GFR>25 or in Diabetics → 0.6-0.8 g/kg/day
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GFR<25 or in Diabetics with RF → 0.3-0.6 g/kg/day
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Protein restriction may delay development of ESRD, but no
definitive conclusions could be made
Prevention:
Treatment of Dyslipoproteinemia
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↑TG (Up to 70% of patients), ↓HDL, ↔ Total-C
 Progression of renal disease
 Cardiovascular morbidity & mortality
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Treatment:
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Based on individual lipid profile, generally NCEP
guidelines are used
Gemfibrozil (Clofibrate accumulates in CRF)
 Statines
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ESRD
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Uremic Toxins:
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urea, guanidine, purine & pyridine derivatives,
aliphatic & aromatic amines, PTH
Secondary Complications:
Mild Renal Dysfunction:
 fluid overload, HTN
 Mod to Severe Renal Dysfunction:
 ↑ K, ↑ P, ↓Ca, Metabolic acidosis,
 Anemia
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Metabolic Effects of Uremia
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Fluid/Electrolytes/Acid-Base:
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Hematologic:
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Anemia, Hemostatic abnorm., Immune suppresion
CVS:
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Fluid retention, ↑K, ↑Mg, ↑P, ↓Ca, Metabolic acidosis
HTN, CHF, Pericarditis, Atherosclerosis, Arrhytmia,
↓ exercise tolerance
Endocrine:
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Hyperpara, Altered thyroid function, Hypophyseal-gonadal
dysfunc, Erythropoietin deficiency
Metabolic Effects of Uremia (Cont.)
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GI:
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Musculoskeletal:
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Lethargy, Tremor, Asterixix, Cramp, Motor weakness, Peripheral
neuropathy
Skin:
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Renal bone disease, Amyloidosis, Extraskeletal calcification
Neurologic:
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Anorexia, Nausea, Vomiting, Delayed gastric emptying, Ulcers, GI
bleeding
Altered pigmentation, Pruritus
Psychologic:
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Depression, Anxiety, Psychosis
Treatment
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Dialysis (HD, PD)
Transplant
Pharmacotherapy
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To Slow the rate of progression
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To manage secondary complications
Conclusion