Definition and prevalence of renal failure - classification of renal failure - Acute renal failure definition , causes , stages , clinical manifestations, investigations and treatment - Chronic renal failure definition , causes, stages , risk factors , clinical manifestations , investigations and treatment. Drug safety during chronic renal dysfunction - Adverse drug effects during chronic renal dysfunction

1. Renal Failure
Management
Dr. Sameh Ahmad Muhamad abdelghany
Lecturer Of Clinical Pharmacology
Mansura Faculty of medicine

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INTRODUCTION
CLASSIFICATION
ACUTE RENAL
FAILURE
CHRONIC RENAL
Failure
DRUG SAFETY
IN CKD
CONTENTS

3. INTRODUCTION

4. 4
Introduction
 Results when the kidneys cannot
remove the body’s metabolic wastes or
perform their regulatory functions.
 It is a systemic disease and is a final
common pathway of many different
kidney and urinary tract diseases.

5. 5
Introduction
 Chronic kidney disease affected 753
million people globally in 2016,
including 417 million females and 336
million males.
 In 2015 it resulted in 1.2 million deaths,
up from 409,000 in 1990.

6. Acute Renal Failure

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Acute Renal Failure
 Definition:
 is an acute and potentially reversible irritability
of the kidneys to perform their normal functions
to maintain homeostasis
 There is a sudden and almost complete loss of
kidney function (decreased GFR) over a period
of hours to days with failure to excrete
nitrogenous waste products and to maintain
fluid and electrolyte homeostasis

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Acute Renal Failure
 Causes:
I. Pre-renal(Functiona)
 Volume Depletion
 Cardiac
 Hepatorenal syndrome
 Drugs: NSAIDs - ACEIs

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Acute Renal Failure
 Causes:
II. Intra-renal(Structural)
 Vascular: e.g Vascular occlusion
 Interstitial: e.g Interstitial nephritis
 Glomerular: e.g glomerulonephritis
 Tubular: e.g ATN

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Acute Renal Failure
 Causes:
III. Post-renal(Obstruction)
 Due to obstruction in Urinary system.
 Sites of obstruction leading to ARF:
o Bladder neck obstruction
o Bilateral ureters
 Urine volume variable

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Acute Renal Failure

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Acute Renal Failure
 Stages
 Onset :
 1-3 days with increased BUN and creatinine and
possible decreased UOP
 may be Asymptomatic
 Oliguric:
 UOP < 400/d, increased BUN, Creatinine,
Phosphates, K, may last up to 14 d
 Impaired glomerular filtration
 Waste cannot be remove & Uremia develops

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Acute Renal Failure
 Stages
 Diuretic :
 UOP increased up to as much as 4000 mL/d but
no waste products
 at end of this stage may begin to see
improvement
 dehydration and electrolyte imbalance due to
excess urination
 Recovery :
 things go back to normal or may remain
insufficient and become chronic(takes months)

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Clinical manifestations
 Severe oliguria/ Anuria
 Nausea / Vomiting
 Lethargy
 Dehydration
 Acidotic breathing
 Altered consciousness
 Irregular cardiac rate, rhythm
 Edema
 Hypertension

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Clinical manifestations

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Investigations
 LAB
 Blood examination:
 Anemia
 Raised serum creatinine level, blood urea
 Electrolytes: K , Na , Ca
 PH: Acidosis
 Complete blood count
 Urine examination:
 Protienuria, Hematuria, presence of casts

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Investigations
 Radiological
 USG
 Structural abnormalizes, calculi
 IVP
 Acute tubular necrosis
 Radionuclide studies
 Evaluate GFR, renal blood flow
 Renal biopsy
 Ultimate cause

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Investigations

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Treatment
 Immediate treatment of pulmonary edema and
hyperkaliemia
 Remove offending cause or treat offending cause
 Dialysis as needed to control hyperkaliemia,
pulmonary edema, metabolic acidosis, and
uremic symptoms
 Adjustment of drug regimen
 Usually restriction of water, Na, and K intake,
but provision of adequate protein
 Possibly phosphate binders

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Treatment
 Medical treatment
 Fluid and dietary restrictions
 Use of diuretics
 Maintain Electrolytes
 May need dialysis to jump start renal function
 May need to stimulate production of urine
with IV fluids, Dopamine, diuretics, etc.
 Hemodialysis

21. CHRONIC
RENAL FAILURE

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Chronic Renal Failure
 Definition:
 It is a permanent irreversible destruction of
nephron leading to severe deterioration of renal
function, finally resulting to end stage renal
disease
 Defined as either presence of
 Kidney damage
o Pathological abnormalities
 Glomerular filtration rate (GFR)
o <60 ml/min for 3 months or longer

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Chronic Renal Failure
 Causes:
 Glomerulonephritis (the most common
cause in the past)
 Diabetes mellitus
 Hypertension
 Tubulointerstitial nephritis
 Miscellaneous

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Chronic Renal Failure
 Stages:
1) Diminished Renal Reserve
 Normal BUN, and serum creatinine
 absence of symptoms
2) Renal Insufficiency
 GFR is about 25% of normal
 BUN Creatinine levels increased

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Chronic Renal Failure
 Stages:
3) Renal Failure
 GFR <25% of normal
 increasing symptoms
4) ESRD or Uremia
 GFR < 5-10% normal
 creatinine clearance <5-10ml/min resulting
in a cumulative effect

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Chronic Renal Failure
 Risk factors:
 Old age
 Family history
 Diabetes
 Obesity
 HTN
 Cardiac diseases
 Previous acute kidney injury
 Smoking

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Chronic Renal Failure

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Clinical manifestations
 Early symptoms
 Weakness
 Anorexia
 Nausea
 Failure to thrive
 Unexplained anemia
 Late symptoms
 Pericarditis
 Congestive cardiac failure
 Altered sensorium

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Complications
 Azotemia
 Metabolic acidosis
 Electrolyte imbalance
 Chronic cardiac failure
 HTN
 Severe anemia

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Clinical manifestations

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Clinical manifestations

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Investigations
LAB
 Blood examination:
 Decreased hematocrit, Hb%, Na+, Ca++,
HCO-3, increased K+ & phosphorus
 Renal function test
 Gradual increase in BUN, uric acid &
creatinine
 Urine examination:
 Variation in specific gravity, increased urine
creatinine, change in total urine output

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Investigations
Radiological
 X-Ray
 Chest, hands, knees, pelvis, spine to detect
bony defect
 ECG, IVP, MCU, radio nuclide imaging
 Extent of complications

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Investigations

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Treatment
 Conservative management
 Correction of reversible component of renal
dysfunction
 Preservation of renal function
 Treatment of metabolic problems
 Optimization of growth
 Preparation for treatment of ESRD
 Treat for infection, accelerated hypertension,
CCF, obstruction of urine flow to improve
renal function

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Treatment
Medical treatment
 IV glucose and insulin
 Na bicarb, Ca, Vit D, phosphate binders
 Fluid restriction, diuretics
 Iron supplements, blood, erythropoietin

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Treatment
Dietary therapy
 Low protein diet
 Severe protein restriction may produce
protein calorie malnutrition
 Salt restriction in patients with
hypertension and fluid overload

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Treatment
Dietary therapy
 Patients with salt losing nephropathy
should take a liberal amount of salt and
water
 If the GFR falls <10 ml/min/1.73m2,
potassium intake should be restricted.
(hyperkalemia may develop)
 Vit D is essential to raise the serum
calcium and suppress parathormone
secretion

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Treatment
Dialysis
 Peritoneal dialysis
 Hemodialysis
Renal transplantation

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Treatment
Peritoneal dialysis

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Treatment
Hemodialysis

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Treatment

43. DRUG SAFETY
IN CKD

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Drug-Related adverse
safety events in CKD
 Occurs in 50% of patients with estimated
GFR (eGFR) <60 ml/min
 Risk factors
 Non-white
 Older age
 ACEIs/ ARB use
 Diabetes
 More advanced CKD

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Drug-Related adverse
safety events in CKD
 Modes of Drug-Related Adverse Events in
CKD
i. Direct kidney injury
ii. Dosing error
iii. Drug-drug interaction

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Drug Elimination in CKD
 Adjustments usually needed when >25-30%
of active drug/metabolite eliminated renally:
o Azithromycin 5-12%
o Moxifloxacin 15-21%
o Pioglitazone (Actos) 15-30%
o Ciprofloxacin 30-57%
o Amoxicillin 50-70%
o Digoxin 57-80%

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I- Drugs To avoid in CKD
1. NSAIDs
 Injure kidneys directly
o Induce acute kidney injury (AKI) from “pre-
renal” or ATN
o Interstitial nephritis
o Nephrotic syndrome
 Decrease kidney potassium excretion →
hyperkalemia
 Decrease sodium excretion → HTN, edema

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I- Drugs To avoid in CKD
2. Oral Sodium Phosphate Preparations
 Hyperphosphatemia + volume depletion
 Acute Phosphate Nephropathy
o Ca-phosphate deposits in tubules
& interstitium
o Leads to AKI/ CKD within days to months

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I- Drugs To avoid in CKD
3. Iodinated Contrast
 Leads to AKI
 Risk Factors
 CKD (esp. eGFR <30 ml/min/1.73m2)
 Diabetes, CHF, gout
 Dehydration
 Concurrent use of NSAIDs or RAAS-
antagonists

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I- Drugs To avoid in CKD
4. Gadolinium
 Linked to nephrogenic systemic fibrosis (NSF)
 Increased risk with decreased kidney function
(AKI, CKD, post-transplant)
 Avoid gadolinium in patients with eGFR <30
ml/min

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II- Drugs require cautions in CKD
1. Antihypertensives: RAAS antagonists
 Can lead to AKI, hyperkalemia
 Risk management
 Avoid in patients with renal artery stenosis
 Assess eGFR and serum K+ 1 week after initiation
or ↑dose
 Prior to contrast, major surgery, conditions that
predispose to dehydration - consider temporarily
decrease
 Stop or reduce if SCr increase > 30% or serum K+
> 5.5 mEq/L

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II- Drugs require cautions in CKD
2. Gabapentin
 Many cases with GFR < 90 ml/min
developed side effects
 Mostly ESRD patients had side effects

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II- Drugs require cautions in CKD
3. Antimicrobials
 Most require renal dose adjustments:
o Common exceptions: Ceftriaxone,
moxifloxacin, macrolides, doxycycline,
clindamycin, linezolid
 Careful monitoring of drug levels needed
for:
o Vancomycin. Aminoglycosides

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II- Drugs require cautions in CKD
3. Antimicrobials
 Trimethoprim/ sulfamethoxazole
 May ↑SCr slightly due to ↓renal tubular
creatinine excretion
 no change in GFR.
 Distinguish from AKI due to drug allergic
interstitial nephritis
 Hyperkalemia
 Imipenem/ cilastatin
 High seizure risk in CKD patients, use
carbapenem in CKD

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II- Drugs require cautions in CKD
4. Metformin
 eGFR 45 to 60 mL/min/1.73m2
 Continue metformin use and ↑ monitoring of
eGFR to every 3 - 6 months
 eGFR 30 to 45 mL/min/1.73m2
 Use metformin with caution with lower dose
(50% maximal)
 eGFR < 30 mL/min/1.73m2
 Stop metformin

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II- Drugs require cautions in CKD
5. Hypoglycemics
 Sulfonylureas
 Dose adjustment needed for renally excreted
drugs: chlorpropramide, glyburide
 Avoid above two if eGFR < 50 ml/min
 Insulin
 Partially renally excreted and dose adjustment
may be needed for eGFR <30 ml/min

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II- Drugs require cautions in CKD
6. Lipid-lowering drugs
 Statins
 Dose adjustments needed when eGFR <30
ml/min for fluvastatin, lovastatin, pravastatin,
rosuvastatin and simvistatin
 Fibrates
 Associated with AKI esp. in CKD patients
 May transiently raise SCr by increased
creatinine production rather than decreased
GFR

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III- Awareness of drug-drug
interactions in patients
1. Rhabdomyolysis with Statins
 Due to Cytochrome P450 3A4 interactions
 Azoles (ketoconazole the worst)
 Diltiazem and Verapamil
 Clarithro and Erythro >>> Azithro
 Ritonavir in HIV patients
 Cyclosporine and Tacrolimus

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III- Awareness of drug-drug
interactions in patients
2. Bisphosphonates
 Bisphosphonates for eGFR > 30 mL/min/ 1.73
m2 with normal Ca, phosphoate, intact PTH
showing osteoporosis .
 Long term treatment with bisphosphonates may
cause or exacerbate adynamic bone disease.

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Avoiding drug toxicity in CKD
 Minimizing Risk of Adverse Drug
Events
 Minimize pill burden as possible
 Review medications carefully for
o Dosing
o Potential interactions
 Educate patient on:
o OTC meds to avoid (mainly NSAIDs)
o Signs/symptoms of potential drug adverse
effects

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Avoiding drug toxicity in CKD
 Dosing Adjustments
 Don’t rely on SCr alone – calculate eGFR or Cr
clearance
 Cannot rely on eGFR in AKI
 When in doubt, look up dosing adjustment/
potential interactions

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2CONTACT
 Email: dr.samghany@gmail.com
 Facebook: Sameh abdelghany
(https://www.facebook.com/samghany)
 SlideShare: Sameh abdelghany
(https://www.slideshare.net/samghany)
 Tel: 01003798288

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