1. Acute Renal Failure
Percy Pentecost MD

2. Objectives To understand: 3 major etiologies of ARF
Pathophysiology of:
prerenal ARF
Postrenal ARF
Intrarenal ARF
Basic evaluation and treatment of ARF 2

3. Definitions
Acute Renal Failure: abrupt and sustained decline in renal function resulting in an accumulation of nitrogenous waste products and uremic toxins
Oliguria: Urine output less than 400 mL/ 24°
Anuria: Urine output less than 100 mL/ 24°
Azotemia: Increase in serum concentration of nitrogenous waste products 3

4. Incidence Community Acquired ARF: Hospital Acquired ARF:
Prerenal70% of cases
Mortality 7%
Hospital Acquired ARF:
15-20% of ICU patients
Ischemic or Toxic injury in 60% of these cases
Mortality 50-70% 4

5. Risk Factors Advanced Age Preexisting Renal Disease Diabetes
Cardiac Disease
Liver Disease
“Older Sicker Patients
“Internal Medicine Patients” 5

6. 3 Major Etiologies of ARF
Prerenal
“before the kidney”
Postrenal
“after the kidney”
Intrarenal
“within the kidney” 6

7. Prerenal ARF

8. Prerenal Factoids Very Common Often reversible within 24-48 hours
Caused by renal hypoperfusion and decreased GFR
Not associated with significant tubular injury…
…unless sustained

9. Prerenal Causes Hypovolemia: Low Cardiac Output (real and effective):
Hemorrhagic Shock, Dehydration, Liver Failure with Low Albumin
Low Cardiac Output (real and effective):
CHF, Drugs*
Systemic Vasodilation:
Sepsis, Drugs*, Hepatorenal Syndrome
Renal Vasoconstriction:
Renal Artery Stenosis, Embolism, or Disection 9

10. Prerenal--Drugs
Changes in tone of afferent/ efferent arterioles will affect RBF and GFR
ASA and NSAIDS cause this >
ACEIs and ARBs cause this > 10

11. Prerenal Diagnosis Bun to Creatnine greater than 20 / 1 Classically
FENa < 1% and Urine Sodium is low (<20)
Kidneys avidly absorbing Na to increase perfusion pressure
Urine Osms and SG are high
Urine is concentrated
Urine Sediment is bland (Minimal RBCs and WBCs)
No tubular / glomerular injury or inflamation
History suggests
Nausea, vomiting, diarrhea, immobile with no access to water, etc… 11

12. Prerenal--Treatment Supportive Care Improve Renal Hemodynamics
IVFs
Minimize Nephrotoxic drugs
Stop ACEi, NSAIDS
Prevention
Recognize Early 12

13. Postrenal ARF

14. Postrenal Failure Factoids
5% of all cases of acute renal failure
Corrected within 1 week of onset prognosis excellent
Persists > 12 weeks: interstitial fibrosis / tubular atrophy
Irreversible
Variable presentation:
Anuria with complete obstruction
Polyuria alternating with oliguria in partial obstruction
Post-obstructive diuresis may lead to volume depletion 14

15. Postrenal Causes Urethral: Bladder: Ureters Urethral Stricture
Clogged Foley
BPH
Bladder:
Bladder Tumor
Neurogenic Bladder
Clots
Ureters
Stones
Sloughed Papilla
AAA
Abdominal Cancers
Abdominal Compartment Syndrome
Retroperitoneal Fibrosis
Lymphadenopathy
Post Surgical

16. Postrenal Failure Diagnosis
Clinical Suspicion Important—Who is going to get this?
BUN/Cr ratio may be high (like in pre-renal)
BUN diffuses back into system
K may be high
Type IV RTA
UA with blood is common
FeNa, Urine sodium, Urine Osms: normal
Ultrasound
Hydronephrosis
Obstructing Lesion?
Consider Noncontrast CT for stones 16

17. Postrenal Failure Treatment
Put in Foley (or check for patency)
Address Underlying Cause
Urology Consult may be helpful
Tumor? Stone removal?
Watch for Post-obstructive Diuresis 17

18. Intrarenal ARF

19. Intrarenal--Causes Ischemic Tubular Injury (formerly ATN)
Nephrotoxic Injury (Formerly ATN)
Acute Interstitial Nephritis
Intra-tubule Deposition/Obstruction
Atheroembolic
Thrombotic Microangiopathy
Glomerulornephritis 19

20. Ischemic and Toxic Injury
Intrarenal ARF
Ischemic and Toxic Injury

21. Intrarenal Ischemic/Toxic Injury Phases
Initiation
Sustained Prerenal state (poor O2 delivery)
Toxic Injury
Extension and Maintenance
Altered transport, adhesion, etc.
Cell sloughing into tubule lumen
Leukocytes, cytokines, etc.
Now vascular blockage too...
Recovery
After insults are gone.... 21

22. Intrarenal Ischemic/Toxic Injury Diagnosis
Prerenal Azotemia:
BUN/Cr >20:1
Specific Gravity >1.020
FENA <1%
Uosm > 500
Una <25
Bland Sediment
Tubules working no signs of injury
ATN / AKI:
BUN/Cr ~10-15:1
Specific Gravity ~ 1.010
FENA >2%
Uosm
Una > 40
Muddy Brown Casts
Tubules injured and not working 22

23. Intrarenal Ischemic/Toxic Injury Toxins
Partial List
Aminoglycosides
Amphotericin B
Iodinated contrast
Cisplatin
Heme pigments
Hemolysis
rhabdomyolysis
Notes
From ischemic or due to contrast onset is rapid.
From aminogylcosides onset often delayed
As a general rule, toxic injury is dose dependent
Aminoglycosides may be less toxic given daily 23

24. Intrarenal Ischemic/Toxic Injury Treatment
Remove the insult
Supportive
Watch / Replace Electrolytes
Maintain fluid balance 24

25. Intrarenal ARF
AIN

26. AIN Factoids AIN = Acute Interstitial Nephritis
Hypersensitivity drug reaction most common cause 26

27. AIN Drugs Drugs associated with AIN: More drugs associated with AIN:
Beta-lactam antibiotics
Sulfonamides
Vancomycin
Ciprofloxacin
Rifampin
Acyclovir
Captopril
Aspirin
NSAIDS
Diuretics
More drugs associated with AIN:
Polymyxin
Erythromycin
Indinavir
Alpha-interferon
Cimetidine
Allopurinol
Azathioprine
Diazepam
Tetracycline
Phenobarbital
Clofibrate
Carbamazepine
Sulfinpyrazone
Phenindione 27

28. AIN Drug Factoids
Original reports on methicillin-associated AIN reported occurrence after days of drug therapy
Currently, reported to occur after 7-14 days of therapy
Can occur within 2-3 days after re-exposure to particular drug
Can occur de novo in response to previously tolerated drug (e.g. NSAIDs) 28

29. AIN Diagnosis “Classic” presentation (less than 30% of patients)
Elevated Cr
Fever
Rash
Eosinophiluria
Clinical suspicion is important
Renal biopsy is gold standard 29

30. AIN Treatment Supportive Discontinue potentially offending drugs
May need Renal Consult:
Steroids may help (no RCTs to support)
Window of therapy for steroids is 7-14 days after onset of azotemia
Plasmapheresis if anti-tubular basement membrane ABs on biopsy
Prognosis: Usually reversible if drug stopped quickly (1 week) 30

31. Intrarenal ARF
Tubular Obstruction

32. Tubular Obstruction 32 Pathophysiology:
Drugs/compounds precipitate in tubules
Form obstructing crystals
A Partial List:
Methotrexate
Intravenous acyclovir
Sulfadiazine
Indinavir
Ethylene glycol toxicity
Calcium oxalate crystals
Urate crystal nephropathy
After cancer chemotherapy
Light chains in Multiple Myeloma 32

33. Tubular Obstruction Diagnosis
Elevated Uric Acid (Post Chemotherapy)
SPEP/UPEP (Multiple Myeloma)
Medication List
History 33

34. Tubular Obstruction Treatment
Prevention Best Cure
Adequate Volume
Specific Therapies in some instances
Theophyline for Cisplatin
Supportive 34

35. Intrarenal ARF
Atheroembolic

36. Atheroembolic Pathogenesis
Sometimes occurs spontaneously
Anticoagulation may precipitate it
Usually after manipulation of aorta
Surgery
Angiography
Embolization of cholesterol into arterioles and glomerular capillaries
inflammatory cell infiltrate
ischemic tubular injury 36

37. Atheroembolic Diagnosis
Cutaneous manifestations: Livedo reticularis, digital infarcts
Other organs involves: bowel ischemia, CNS disturbance
Eosinophilia
Low C3 levels (in some patients—15%)
Elevated ESR
History 37

38. Atheroembolic Treatment
Supportive
Treat diabetes, hypertension, dyslipidemia
Discontinue Anticoagulents
Management of vascular risk factors
Prognosis traditionally thought to be poor
comorbid cardiovascular disease 38

39. Thrombotic Microangiopathy
Intrarenal ARF
Thrombotic Microangiopathy

40. Thrombotic Microangiopathies Etiology
Pathophysiology:
Clotting cascade imbalance
Small vessel blockage and ischemia
Multiple Precipitating factors
DIC
TTP
Infectious Diarrhea (Ecoli 0157, Shiga Toxin)
SLE
HIV
Drugs 40

41. Thrombotic Microangiopathies Diagnosis/Treatment
Low Platelets on CBC
RBC fragments on peripheral smear
Clotting cascade imbalance
Small vessel ischemia
Multiple Precipitating factors
DIC
TTP
Infectious Diarrhea (Ecoli 0157, Shiga Toxin)
SLE
HIV 41

42. Acute Glomerulonephritis
Intrarenal ARF
Acute Glomerulonephritis

43. Glomerulonephritis Pathogenesis
Deposition of complexes in glomeruli
Cause damage and inflammation
Many Precipitating Factors
Bacterial infection
Group A Strep
Viral Infection
URI
Hep C
Rheumatalogic Disease
SLE
Vasculitis 43

44. Glomerulonephritis Diagnosis
Urinalysis with “Active Sediment”
RBCs and WBCS
Dysmorphic RBCs
RBC and WBC Casts
C3 levels Low (C3 represents intrinsic and extrinsic pathway)
ASO titer (post streptococcal)
Hepatitis Panel (Hep C)
Skin Biopsy (IgA Nephropathy and vasculitis)
RF, ANA, ANCAs, etc. (SLE, vasculitis, etc.)
Renal Biopsy 44

45. Glomerulonephritis Treatment
Treat Infections
“breaks the cycle”
Treat Underlying Diseases
Steroids and/or Cyclophosphamide
Renal and Rheumatology Consults 45

46. Questions? 46