ARF lec 8

Acute Renal Failure (ARF)

Mahmoud Ibrahim Elseidy, PhD Lecturer of Clinical Pharmacy and Pharmacy Practice Member of the American College of Clinical Pharmacology

Kidney Background

Functional Units: NephronsKey Functions:

• Removal of waste products (e.g., urea)

• Elimination of excess fluid, electrolytes, and drugs

• Regulation of blood pressure (BP)

• Endocrine functions:

  • Erythropoietin

  • Vitamin D activation

  • Regulation of acid-base imbalance

Acute Renal Failure Definition

Definition: Acute decline in kidney function or Glomerular Filtration Rate (GFR);Usually occurs over hours to weeksAssociated with build-up of waste products in the bodyOften involves volume changes

Criteria and Classification of AKI

KDIGO Definition of AKI:

• Increase in Serum Creatinine (SCr) of ≥0.3 mg/dL within 48 hours

• Increase in SCr ≥ 1.5 times baseline (known or presumed within previous 7 days)

• Urinary volume < 0.5 mL/kg/hour for at least 6 hours

Urinary Output Classification

• Anuric: <50 mL/24 hours; associated with worse outcomes

• Oliguric: <0.5 mL/kg/hour ≥ 12 hours

• Nonoliguric: >500 mL/24 hours

  • Better outcomes and easier management due to fewer issues with volume overload

Staging of AKI

• RIFLE Classification (2004)

• AKIN Criteria (2007)

• KDIGO Staging (2012)

  • Risk: SCr increase to 1.5 × baseline or GFR decrease > 25%

  • Stage 1: ≥ 0.3 mg/dL increase or 1.5–2.0 × baseline

  • Stage 2: SCr increase to 2–3 × baseline

  • Stage 3: SCr increase to 3 × baseline or SCr ≥ 4 mg/dL with acute rise of > 0.5 mg/dL; initiation of renal replacement therapy (RRT)

  • Loss of kidney function (Complete loss for > 4 weeks)

  • End-stage disease (Complete loss for > 3 months)

Common Complications of AKI

• Fluid overload

• Acid-base imbalances

• Electrolyte disturbances

Investigations

Laboratory TestsKey Markers:

• Serum Creatinine (SCr)

• Blood Urea Nitrogen (BUN): Assesses renal function + hydration status

• Electrolytes: Na, K, Mg, PO4, Bicarbonate levels

• Complete Blood Count (CBC): To check for anemia or infection

Urinalysis:

• Protein, RBC, WBC levels

• Specific gravity and sediment examination for cellular casts

Functional Tests

• Fractional Excretion of Sodium (FENa): Differentiates pre-renal from intrinsic renal causes

• Urinary Sodium: Assesses tubular function

Imaging Studies

• Ultrasound (Renal US): Checks for obstructions and kidney size

• CT Scan/MRI: Advanced imaging when necessary

• Renal Biopsy: Considered in selected cases for definitive diagnosis

Special Tests

• Drug Levels: For potential drug-induced nephrotoxicity

• Serologic Tests: ANA, ANCA, complement levels in suspected glomerulonephritis or vasculitis

Types of AKI

Community-acquired AKI

• Incidence: Relatively low (0.02%) in healthy individuals

• Higher incidence in patients with Chronic Kidney Disease (CKD) (up to 13%)

• High survival rate (70%–95%)

• Typically caused by a single insult, frequently drug-induced

• Often reversible but may progress to CKD

Hospital-acquired AKI

• Moderate incidence (2%–5%)

• Survival rate: 30%–50%

• Can be due to single or multiple insults to the kidney

• 50% incidence in ICU patients, with mortality rate 4–5 times higher

Estimating Kidney Function in AKI

Estimated Glomerular Filtration Rate (eGFR)

• Indicated instead of 24-hr urine collection

• Cockcroft-Gault Equation: Considers age, sex, body weight, and serum creatinine (SCr)

• MDRD Equation: More accurate in CKD; does not require weight

• CKD-EPI Equation: Greater precision, especially at higher GFRs

Limitations

• SCr-based equations assume stable function, unsuitable for AKI

• May not be accurate in very obese or malnourished individuals

Risk Factors Associated with AKI

• Advanced age

• Preexisting CKD (eGFR < 60 mL/minute/1.73 m^2)

• Volume depletion due to various causes

• Nephrotoxic medications

• Urinary tract obstruction

Nephrotoxic Agents and Medications

• Intravenous radiographic contrast

• Aminoglycosides and amphotericin

• NSAIDs and COX-2 inhibitors

• ACE inhibitors and ARBs

• Immunosuppressants like cyclosporine and tacrolimus

• Certain antibiotic combinations (e.g., piperacillin/tazobactam plus vancomycin)

Classification of AKI

Divided into four categories: Prerenal AKI, Functional AKI, Intrinsic AKI, and Postrenal AKI

Prerenal AKI

• Initially, the kidney is undamaged

• Causes:

  • Systemic hypoperfusion (e.g., hemorrhage, volume depletion)

  • Isolated kidney hypoperfusion (e.g., renal artery stenosis)

• Physical Examination: Hypotension, signs of volume depletion

• Urinalysis: Initially normal but concentrated

• Key Lab Values:

  • BUN/SCr ratio > 20:1

  • Urinary sodium < 20 mEq/L

  • FENa < 1%

  • FeU < 35%

Functional AKI

• Kidney is undamaged; often categorized as prerenal azotemia

• Mechanism: Reduced glomerular hydrostatic pressure without hypotension

• Common Causes: Medication-related (cyclosporine, NSAIDs)

• Urinalysis: Often concentrated urine

Intrinsic AKI

• Direct damage to the kidney affecting specific structures

• Common Form: Acute Tubular Necrosis (ATN)

• Other types include: Acute Interstitial Nephritis (AIN), vasculitis

• Symptoms: Generally normotensive; may show allergic reactions

• Diagnosis:

  • Urinalysis shows granular casts

  • Serum BUN/SCr ratio 10–15:1

  • Urinary sodium > 40 mEq/L

  • FENa > 2%

  • FeU > 50%

Postrenal AKI

• Related to obstructive causes

• Causes: Kidney stones, BPH, cancers

• Physical Examination: Distended bladder, enlarged prostate

• Lab Values:

  • BUN/SCr ratio 10–15:1

  • Urinary sodium > 40 mEq/L

  • FENa > 2%

  • FeU > 50%

Prevention of AKI

• Control underlying cause (sepsis, diarrhea, heart failure)

• Avoid nephrotoxic drugs

• Ensure adequate hydration, especially before contrast media

• Monitor and correct electrolyte imbalances promptly

Treatment and Management of Established AKI

Prerenal Azotemia

• Correct primary hemodynamics with IV fluids (normal saline/lactated Ringer)

• Manage blood pressure and administer blood products, if needed

• Discontinue medications affecting renal hemodynamics (ACEIs, ARBs, NSAIDs)

Intrinsic AKI

• Remove causative abnormalities or toxins

• Manage fluid and electrolytes

• Provide nutritional support (high protein, more calories)

Postrenal AKI

• Monitor fluid balance

• Early identification and urology/radiology consultation is crucial

Drug-Induced Nephropathy Risk Factors

• History of CKD

• Advanced age

• Critical illness

• Concurrent nephrotoxic medications

Drug-Induced Nephropathy Epidemiology

• 7% of all drug toxicities

• 18%–27% of AKI in hospitals

• 1%–5% of NSAID users in the community

• Most Implicated Medications: Aminoglycosides, NSAIDs, ACEIs, contrast dye, amphotericin, piperacillin/tazobactam plus vancomycin

Drug-Induced Nephropathy Pseudo-nephrotoxicity

• Drugs inhibiting tubular secretion of creatinine (trimethoprim, cimetidine)

• Drugs increasing BUN (corticosteroids, tetracycline)

• Drugs interfering with creatinine assay (cefoxitin)

Drug-Induced Nephropathy Acute Tubular Necrosis (ATN)

• Common in inpatient setting

• Aminoglycosides: Incidence varies

• Radiographic Contrast Media: 3rd leading cause of inpatient AKI

• Cisplatin: Incidence: 6%-13%

• Amphotericin B: Increases incidence with cumulative dose

Drug-Induced Nephropathy Functional AKI

• Related to alterations in kidney blood flow influenced by medications

• Common drugs: ACEIs, ARBs, NSAIDs

Drug-Induced Nephropathy Tubulointerstitial Disease

• Acute: Rapid loss of kidney function, systemic symptoms

• Chronic: Slow decline in kidney function

Drug-Induced Nephropathy Tubulointerstitial Disease Acute Allergic Interstitial Nephritis

• Incidence: Up to 3% of AKI cases

• Medication-Induced: Commonly β-lactams and NSAIDs

Drug-Induced Nephropathy Tubulointerstitial Disease Chronic Interstitial Nephritis

• Often irreversible; common cause is long-term Lithium use

• Presentation: Initial asymptomatic, then increased BP, BUN, and SCr

Drug-Induced Nephropathy Tubulointerstitial Disease Papillary Necrosis

• Cause: Long-term analgesic use

• Presentation: Slow evolution, more frequent in women

Postrenal (Obstructive) Nephropathy

• Resulting from urine flow obstruction

• Causes: Renal tubular obstruction, extrarenal urinary tract obstruction

Postrenal (Obstructive) Nephropathy Glomerular Disease Overview

• Clinical Presentation: Proteinuria ± decrease in GFR

• Drug-Induced Glomerular Disease:

  • NSAIDs related to acute allergic interstitial nephritis

  • Heroin can cause direct toxicity or ESRD

  • Parenteral Gold causes immune complex formation in glomerular capillaries