In the name of God Chronic Renal Failure
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Transcript In the name of God Chronic Renal Failure
In the name of God
Chronic Renal Failure
By:
Dr. Shahram Ala
(PharmD, BCPS)
Kidney
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
Other functions of kidneys
Renin secretion
Erythropoietin secretion
Activation of vit D3 (Calcitriol)
Renal Failure
up to 75% of function can be lost before it is
noticeable
ARF: Rapid onset,
usually reversible,
rapid reduction in
urine volume
CRF: Slow onset,
progressive, is not
reversible
Treatment Modalities
Hemodialysis
Peritoneal Dialysis
Renal Transplant
In 1950s, Life expectancy of ESRD patients was just
a few days to weeks
Classification
Worldwide ESRD
CRF & ESRD
CRF and ESRD are significant causes of
morbidity & mortality
Analgesic Nephropathy
Tubulointerstitial renal disease (Papillary necrosis and
interstitial nephritis) due to ingestion of a mixture of 2
analgesics usually with codeine or caffeine
More prevalent in females (5-7.1 times) with peak
incidence between 4th and 5th decade
Salt-wasting nephropathy, ↓urine concentrating &
acidifying capacity
Symptoms: flank pain, pyuria, hematuria, urethral
obstruction
Analgesic Nephropathy (cont.)
Mechanism: oxidative metabolite of
acetaminophen beside reduced glutathione
capacity (due to ASA)
Management: abstinence from NSAIDs &
combination analgesics, high fluid intake (if
possible), management of ESRD is similar to
other causes
Medication Use
Both HD & PD patients receive a median of 8
different drugs including:
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
Most patients are symptom free until renal
function is <25% normal
At renal function <10% normal, uremic
symptoms occurs
At renal function<5%, dialysis or transplant is
required
Intact
nephron hypothesis
Pathogenesis
Glomerular capillary hypertension
Microalbuminuria or proteinuria
Increased renal plasma flow (with high Pr Intake)
Dyslipoproteinemia (esp. TG-rich apo-Blipoproteins)
Clinical assessment
Evaluation of renal function
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)
Microalbuminuria: 30-300 mg/24h
Overt proteinuria: >300 mg/24h
Dipstick test (Reagent strips)
Alb/Cr : 30-300 µg/mg (Microalbuminuria)
Prevention
Antihypertensives
Dietary Protein Restriction
Treatment of Dyslipoproteinemia
Intensive Glu Control (in Diabetic patients)
HTN & CRF
HTN is both a cause and a result of RF
HTN causes glumerolar hyperperfusion leading to
progressive renal damage
Goal of BP:
130/85 (in patients with some degree of renal failure)
125/75 (in patients with proteinuria >1gr)
Prevention:
Which Antihypertensives?
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
ACEIs+CCBs
Prevention:
Dietary Protein Restriction
There is an association between “Protein ingestion”
&“GFR” and “Renal Plasma Flow”
For GFR>25 or in Diabetics → 0.6-0.8 g/kg/day
GFR<25 or in Diabetics with RF → 0.3-0.6 g/kg/day
Protein restriction may delay development of ESRD, but no
definitive conclusions could be made
Prevention:
Treatment of Dyslipoproteinemia
↑TG (Up to 70% of patients), ↓HDL, ↔ Total-C
Progression of renal disease
Cardiovascular morbidity & mortality
Treatment:
Based on individual lipid profile, generally NCEP
guidelines are used
Gemfibrozil (Clofibrate accumulates in CRF)
Statines
ESRD
Uremic Toxins:
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
Metabolic Effects of Uremia
Fluid/Electrolytes/Acid-Base:
Hematologic:
Anemia, Hemostatic abnorm., Immune suppresion
CVS:
Fluid retention, ↑K, ↑Mg, ↑P, ↓Ca, Metabolic acidosis
HTN, CHF, Pericarditis, Atherosclerosis, Arrhytmia,
↓ exercise tolerance
Endocrine:
Hyperpara, Altered thyroid function, Hypophyseal-gonadal
dysfunc, Erythropoietin deficiency
Metabolic Effects of Uremia (Cont.)
GI:
Musculoskeletal:
Lethargy, Tremor, Asterixix, Cramp, Motor weakness, Peripheral
neuropathy
Skin:
Renal bone disease, Amyloidosis, Extraskeletal calcification
Neurologic:
Anorexia, Nausea, Vomiting, Delayed gastric emptying, Ulcers, GI
bleeding
Altered pigmentation, Pruritus
Psychologic:
Depression, Anxiety, Psychosis
Treatment
Dialysis (HD, PD)
Transplant
Pharmacotherapy
To Slow the rate of progression
To manage secondary complications
Conclusion