1. Acute Renal Failure for the Intern

2. 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

3. Anatomy 1 Renal Arteries Kidneys Glomerulus Collecting system Ureter
Bladder
Urethra
Renal Vein

4. 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.

5. 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
Completely filtered
Not secreted
Not reabsorbed / transported
Measure the glomeular filtration of a substance within the kidneys
Serum Creatinine Concentration

6. 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

7. 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

8. 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 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

9. 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.

10. 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!

11. Classification of ARF Etiology Urine Output Pre-Renal Intrinsic Renal
Post-Renal
Urine Output
Polyuria > 3 liters / day
Oligouria: 400 – 100 cc/day
Anuria: < 100 cc / day

12. 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!

13. 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.

14. Urine Microscopy a

15. Urine Microscopy, cont.
Renal Tubular Cast
Dysmorphic RBC

16. 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)

17. Pre-Renal ARF Is the patient dry? Treatment? Etiology
FENa < 1 %
FEUrea < 35 %
BUN / Cr ratio
Urine Osm and SG
Urine Volume
Heart Rate & BP
Pulse Pressure
Skin Turgor
Mucous Membranes
Thirst
Treatment?
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)
Urine Na * Plasma Cr * 100
Plasma Na & Urine Cr

18. NSAID’s and ACE-I in the kidneys
ACE-I inhibit arteriolar constriction
NSAID
Inhibit PG-mediated dilatation

19. Post-Renal ARF Laboratory Evaluation Radiographic 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).
Etiology of Obstruction?
Foley malfunction
Prostatic obstruction
Neurogenic bladder
Post-surgical complication
Retroperitoneal fibrosis / CA
Bilateral Urolithiasis

20. 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:

21. Acute Tubular Necrosis
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
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

22. Microscopy of ATN

23. 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

24. 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:

25. Contrast Induced Nephropathy
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
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.

26. Contrast Induced Nephropathy Prevention & Treatment
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.

27. In Reality…
ATN is commonly multifactorial – nephrotoxic drugs exposed to kidneys with decreased perfusion
Thadhani, R. et al. N Engl J Med 1996;334:

28. Interstitial Nephritis
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.
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

29. Glomerulonephritis
Low Complement
Renal Presentation
PIGN
MPGN
Systemic Presentation
SLE
SBE
Cryoglobulinemia
Normal Complement
ANCA + RPGN
IgA Nephropathy
Alport’s Syndrome
Goodpasture’s Syndrome
TTP – HUS
Vasculitis
First determine patient has glomerulonephritis (not just nephrotic syndrome).
If active sediment
What are the serum complement levels?
Does the patient have systemic symptoms?
Wegener’s
PAN
Idiopathic ANCA
Any of the nephritic syndromes can be considered an RPGN, if it becomes rapidly progressive!

30. Consultation…
If the patient has glomerulonephritis, you should be talking to nephrology!

31. Vascular Etiology Atheroembolic Small Vessel Disease
Recent intravascular intervention
Livedo reticularis
Low complement
Eosinophilia
Blue toes
Small Vessel Disease
Scleroderma
TTP/HUS
DIC
Malignant HTN

32. 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.

33. 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?

34. 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.

35. Review of ARF

36. Questions?