The document discusses the management of renal failure, detailing acute and chronic renal failure, their causes, clinical manifestations, and treatment options. Acute renal failure is characterized by rapid kidney function loss, while chronic renal failure involves irreversible nephron destruction. The document also highlights drug safety in chronic kidney disease, emphasizing necessary adjustments and drugs to avoid due to their risk of toxicity.

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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