Acute Renal Failure for the Intern

Background and Epidemiology

Affects 5%-7% of all hospitalized patients

20%-70% mortality rate overall

ARF in ICU – 50%-70% mortality rate

Mortality rate unchanged over past 50 years

Anatomy 1

Renal Arteries

Kidneys

Glomerulus

Collecting system

Ureter

Bladder

Urethra

Renal Vein

Anatomy 2

Glomerulus

PCT

Loop of Henle

DCT

Collecting system

130 to 180 liters is filtered across the glomerulus every day. 98 to 99 % of that filtrate is reabsorbed.

Estimations of Renal Function

What do the kidneys do?

How can we measure the function of the kidneys?

What is the “ideal” substance to measure?

What do we commonly use to measure renal function?

Filter the blood

Measure the glomeular filtration of a substance within the kidneys

•Completely filtered

•Not secreted

•Not reabsorbed / transported

Serum Creatinine Concentration

Creatinine

Water soluble breakdown product of creatine from skeletal muscle (and ingested meat, suplements).

Creatinine is released into the circulation at a relatively constant rate.

Creatinine is freely filtered in the glomerulus, and is not metabolized by the kidney.

Approximately 15% of the urinary creatinine is secreted in the proximal tubule (in normally functioning kidney).

Remember: Not all individuals will

have the same amount of creatinine in their blood.

Different drugs can affect the concentration of serum creatinine (without affecting a patient’s renal function).

Cimetidine Trimethoprim

Decrease Creatinine Secretion Rise in serum level by up to 0.5 mg/dl

Effects on Serum Creatinine

Decreased Creatinine Secretion Cimetidine >> Ranitidine & Famotidine Trimethoprim

Interfere with the Assay Acetoacetate (Diabetic Ketoacidosis) Cefoxitin Flucytosine

Enhanced Creatinine Production Large meat meal Creatine containing supplements Rhabdomyolysis

Serum Creatinine and Renal Function

Glomerular Filtration Rate Cockcroft-Gault Method Jelliffe Method MDRD

(140 – age) * weight (kg)

72 * serum Creatinine

(multiply by 0.85 for female)

[98 – 0.8 * (age – 20)] * BSA

1.73 * serum Creatinine

(multiply by 0.9 for female)

186 * sCr ^ (-1.154) * Age ^ (-0.203)

Multiple by 0.743 for female

Multiply by 1.21 for African American

•Assumes albumin = 4.0

•Assumes patient is ~ 1.73 m2

95 +/- 20 ml/min in women

120 +/- 25 ml/min in men

Which formula should you use?

Strengths & Weaknesses MDRD

Underestimates patients with normal renal function

Overestimates patients with severe renal impairment.

Cockcroft-Gault Underestimates patients at older ages Overestimates patients at younger ages

All of these formulas are best used in patient’s with stable renal function. It takes time for the serum

creatinine level to accurately reflect renal function.

We usually use the Modification of Diet in Renal Disease (MDRD) forumula. Levey et al. Ann Intern Med.

Mar 1999.

What is Acute Renal Failure?

Increase in sCr > 0.5 mg/dl (44 umol/l)

Increase in sCr > 2-fold

Decrease in GFR > 50%

Decrease in GFR requiring dialysis

Depends on who you talk to!

Classification of ARF

Etiology Pre-Renal Intrinsic Renal Post-Renal

Urine Output Polyuria > 3 liters / day Oligouria: 400 – 100 cc/day Anuria: < 100 cc / day

Urinalysis

Intrinsic Renal ARF usually has an abnormal urinalysis. Are there casts present? Is there proteinuria

present? If hematuria is present,

are the RBC’s dysmorphic?

YOU SHOULD KNOW HOW TO SPIN A PATIENT’S URINE!

Urinalysis

Collect 10 – 20 ml of freshly voided urine in a sterile specimen container.

Take the sample to the laboratory.

Centrifuge the specimen at 2,500 rpm for 5 minutes.

Decant the supernatent.

Place the specimen on a UA microscope slide.

Urine Microscopy

a

Urine Microscopy, cont.

Renal Tubular Cast

Dysmorphic RBC

Urinalysis Clinical Correlation

Nephritis: “active” urinary sediment with casts, RBC’s, WBC’s.

May be accompanied by HTN, proteinuria, ARF.

Implies inflammation and glomerular damage.

Nephrotic Syndrome: proteinuria without casts.

Proteinuria (GBM defect) Edema (low albumin) Hypoalbuminemia Lipid Abnormalities Hypercoagguable State

(AT III depletion)

Pre-Renal ARF

Etiology Acutely reduced renal perfusion

Aortic dissection Thromboembolic disease Drugs (NSAID, ACEI)

Volume Depletion Bleeding Third Spacing Fluid Dehydration

Relative Hypotension Shock Cardiac failure (Volume depletion)

Is the patient dry? FENa < 1 %

FEUrea < 35 % BUN / Cr ratio Urine Osm and SG Urine Volume Heart Rate & BP Pulse Pressure Skin Turgor Mucous Membranes Thirst

Treatment?

Urine Na * Plasma Cr * 100

Plasma Na & Urine Cr

NSAID’s and ACE-I in the kidneys

NSAIDInhibit PG-mediated dilatation

ACE-I inhibit arteriolar constriction

Post-Renal ARF

Etiology of Obstruction? Foley malfunction Prostatic obstruction Neurogenic bladder Post-surgical complication Retroperitoneal fibrosis / CA Bilateral Urolithiasis

Laboratory Evaluation FENa – variable Urine Osm – variable

Radiographic Evaluation Renal US: hydonephrosis, hydroureter.

Unilateral obstruction often does not cause rise in serum creatinine (unless patient only has a single functional kidney).

Intrinsic Renal ARF

“Active” Urine sediment implies renal involvement.

Categorized based on location of injury:

Tubules Interstitium Glomerulus Vessels

Less common systemic conditions

Pre-eclampsia TTP – HUS

Thadhani, R. et al. N Engl J Med 1996;334:1448-1460

Acute Tubular Necrosis

Most common cause of ARF due to intra-renal causes (~ 75%)

Many causes of ATN Transient ischemic episode Toxic injury to the kidneys Myoglobinuria (Rhabdomyolysis) Heavy metals Contrast exposure

Urinalysis Iso-osmolar (300 – 400 mOsms) Urine Na > 20 FENa > 1 % “Muddy brown casts” are nonspecific,

but sensitive.

Urine Output Oligouria: more tubular damage, longer

recovery. Non-oligouria: less tubular damage,

shorter recovery time.

Still carries a high mortality.

For those who improve 90% will do so within 3 weeks 99% will do so within 6 weeks

Microscopy of ATN

Tubular Necrosis: Ischemia

Etiology Systemic Hypotension

Cardiogenic Shock Distributive Shock (sepsis) Hypovolemia (burns, trauma,

blood loss). Post-Surgical Anesthesia

Distributive Hypoperfusion Thyroid Storm Heart Failure ? Hepato-Renal Syndrome

Tubular cells have a high metabolism (i.e. are sensitive to states of low blood flow, hypoxia, or hypotension).

Continuum with pre-renal azotemia

Tubular Necrosis: Nephrotoxins

Common Drugs: Amphotericin B toxicity is dependent

on the total dose (>3 gram); can also cause an RTA.

Aminoglycosides cause proximal tubule damage resulting in non-oligouric ATN.

Cisplatin is directly toxic to the tubules; also causes a magnesuria and hypomagnesemia.

Methotrexate Radiocontrast IVIG

Thadhani, R. et al. N Engl J Med 1996;334:1448-1460

Contrast Induced Nephropathy

Radiocontrast agents Osmolality

First generation contrast agents had very high osmolality (1500 – 1800 mosm/kg)

Second generation contrast agents have lower osmolality (600 – 800 msom/kg): iohexol

Third generation agents have even lower osmolality (~290 mosm/kg): iodixanol

Ionic versus non-ionic First generation were ionic

compounds, newer products are non-ionic.

Pathogenesis is not fully understood Renal vasoconstriction? Direct toxic effect of contrast? Tubular injury from oxygen radicals?

Patient’s at highest risk Diabetes with renal insufficiency Baseline CKD (sCr > 1.5 mg/dl) High total dose of contrast (> 70 cc) Multiple Myeloma Hypovolemia (or distributive state) Concurrent Nephrotoxic Drugs

Contrast Induced Nephropathy Prevention & Treatment

Prevention: Don’t use contrast (MRI?) Use smallest amounts possible

of non-ionic, low-osmolar contrast media.

Avoid volume depletion Avoid NSAID’s

Sodium Bicarbonate D5W + 3 amps NaHCO3/liter (~130 MEQ)

Run at 3.5 cc/kg*hour (ideal body weight) for 1 hour prior to study, and 1.2 cc/kg*hour for 6 hours after exposure

N-acetylcysteine (Mucomyst) 600 mg PO BID Administer 2 doses prior to study, and 2

doses after study.

In Reality…

ATN is commonly multifactorial – nephrotoxic drugs exposed to kidneys with decreased perfusion

Thadhani, R. et al. N Engl J Med 1996;334:1448-1460

Interstitial Nephritis

Acute Interstitial Nephritis Slight proteinuria +/- Renal tubular acidosis +/- Urine Eosinophils +/- RBC, WBC, and WBC Casts Caused by allergic reaction to

medication / exposure

Chronic Interstitial Nephritis Chronic analgesic abuse Heavy Meatals (lead, cadmium) Sjogren’s Disease Chronic Renal Outlet Obstruction Sickle Cell Anemia Multiple Myeloma

Antibiotic AIN Classic Triad = fever, rash, eosinophilia. Presentation is acute Common Agents

Beta-Lactams (esp Methicillin) TMP/SMX Cephalosporins Rifampin FQ

NSAID AIN Classic triad often absent Presentation subacute, or after months

of use of NSAID.

Glomerulonephritis

First determine patient has glomerulonephritis (not just nephrotic syndrome).

If active sediment What are the serum

complement levels? Does the patient have systemic

symptoms?

Low Complement Renal Presentation

PIGN MPGN

Systemic Presentation SLE SBE Cryoglobulinemia

Normal Complement Renal Presentation

ANCA + RPGN IgA Nephropathy Alport’s Syndrome

Systemic Presentation Goodpasture’s Syndrome TTP – HUS Vasculitis

Any of the nephritic syndromes can be considered an RPGN, if it becomes rapidly progressive!

Wegener’s

PAN

Idiopathic ANCA

Consultation…

If the patient has glomerulonephritis, you should be talking to nephrology!

Vascular Etiology

Atheroembolic Recent intravascular

intervention Livedo reticularis Low complement Eosinophilia Blue toes

Small Vessel Disease Scleroderma TTP/HUS DIC Malignant HTN

Acute Indications for Hemodialysis

AEIOU: Acidosis: Which is not responsive to medical therapy

Electrolytes: Hyperkalemia

Toxic Ingestion: Lithium, TCA, Ethylene Glycol, Methanol, Salicylates, (many others)

Fluid Overload: Especially in heart failure patients

Symptomatic Uremia: Bleeding, encephalopathy, pericarditis.

What do you need to do as the Intern?

Learn about the patient’s history PMHx (CKD, CHF, Cirrhosis). Hospital Course

Recent Surgery? Contrast exposures? Hypoxic episode? Hypotensive episode? New drugs?

Labs Repeat the P2 Check a UA with micro (look at the

microscope slide yourself!) Estimate proteinuria (spot

protein/creatinine ratio)

Is the patient making urine? Post-obstruction (foley, BPH, atonic

bladder, etc) Hypovolemia or Pre-renal

Examine the Patient Vital signs Fluid status (S3, JVD, edema) Mental Status (uremia?) Bleeding (uremia? hypovolemia?) GU Exam +/- Rectal Bladder scan and/or renal US

What is the patient’s volume status?

Intern Evaluation, cont…

What category of renal failure is present? Pre-renal Intrinsic renal Post-renal

Is there an indication for acute hemodialysis?

AEIOU

What can you do to support the patient? Fluid challenge if oligouric / anuric Remove potential nephrotoxins

Dose medications for patient’s GFR Ensure adequate renal perfusion (BP) Electrolyte management Fluid management (especially if h/o CHF,

and/or if patient is anuric!)

Remember that ARF is usually not a disease in itself, but rather the final common pathway of a variety of disease states.

Review of ARF

Questions?