1. Acute and Chronic Renal Failure
Courtney Bunevich, DO
December 19, 2007

2. Acute Renal Failure Rapid decline in the GFR over days to weeks
Serum Cr increases by >0.5 mg/dL
GFR <10mL/min, or <25% of normal

3. Definitions Anuria: No urine output
Oliguria: Urine output < mL/d
Azotemia: Increase in Serum Cr and BUN
May be prerenal, renal, or postrenal
Does not require any clinical findings
Chronic Renal Insufficiency
Deterioration over months to years
GFR mL/min, or 20-50% of normal
ESRD: GFR <5% of normal

4. ARF: Signs and Symptoms
Hyperkalemia
Nausea/Vomiting
HTN
Pulmonary edema
Ascites
Asterixis
Encephalopathy

5. Causes of ARF in Hospitalized Patients
45% ATN
Ischemia, Nephrotoxins
21% Prerenal
CHF, volume depletion, sepsis
10% Urinary obstruction
4% Glomerulonephritis or vasculitis
2% AIN
1% Atheroemboli

6. ARF: Focused History Nausea? Vomiting? Diarrhea?
Hx of heart disease, liver disease, previous renal disease, kidney stones, BPH?
Any recent illnesses?
Any edema, change in
urination?
Any new medications?
Any recent radiology studies?
Rashes?

7. Physical Exam Volume Status Mucus membranes, orthostatics
Cardiovascular
JVD, rubs
Pulmonary
Decreased breath sounds
Rales
Rash (Allergic interstitial nephritis)
Large prostate
Extremities (Skin turgor, Edema)

8. Workup for ARF BMP or RFP Urine Kidney U/S to rule out hydronephrosis
Urine electrolytes and Urine Cr to calculate FeNa
Urine eosinophils
Urine sediment: casts, cells, protein
Uosm
Kidney U/S to rule out hydronephrosis

9. FeNa = (urine Na x plasma Cr) (plasma Na x urine Cr)
PRERENAL
Urine Na < 20 because functioning tubules reabsorb lots of filtered sodium
ATN (unusual)
Postischemic disease: most of UOP comes from few normal nephrons, which handle sodium appropriately
ATN + chronic prerenal disease (cirrhosis, CHF)
Glomerular or vascular injury
Despite glomerular or vascular injury, pt may still have well-preserved tubular function and be able to concentrate Na

10. FeNa FeNa 1%-2% Prerenal-sometimes ATN-sometimes
AIN will have a higher FeNa due to tubular damage
FeNa >2%
ATN
Damaged tubules cannot reabsorb sodium

11. Calculating FeNa after Patient Has Recieved Lasix
Caution with calculating FeNa if pt has gotten loop diuretics in past h
Loop diuretics cause natriuresis that raises U Na-even if the patient is prerenal
So if FeNa>1%, you do not know if this is because patient is euvolemic or because lasix increased the U Na
So, helpful if FeNa still <1%, but not if FeNa >1%

12. Prerenal ARF Hyaline casts can be seen in normal pts
NOT an abnormal finding
UA in prerenal ARF is normal
Prerenal: causes 21% of ARF in hospitalized patients
Reversible
Prevent ATN with volume replacement
Fluid boluses or continuous IVF
Monitor Uop

13. Prerenal causes Hemorrhage Vomiting, diarrhea “Third spacing”
Intravascular volume depletion
Hemorrhage
Vomiting, diarrhea
“Third spacing”
Diuretics
Reduced Cardiac output
Cardiogenic shock, CHF, Tamponade
Systemic vasodilation
Sepsis
Anaphylaxis, Antihypertensive drugs
Renal vasoconstriction
Hepatorenal syndrome

14. Intrinsic ARF Tubular (ATN) Interstitial (AIN)
Glomerular (Glomerulonephritis)
Vascular

15. You evaluate a 57yo man with oliguria and rapidly increasing BUN and Serum Cr
ATN
Acute glomerulonephritis
Acute interstitial nephritis
Nephrotic Syndrome
muddy brown granular casts

16. ATN Muddy brown granular casts (last slide)
Renal tubular epithelial cell casts (below)
epithelial cell cast (cells are larger than WBCs; have nuclei)

17. More ATN
Broad casts (form in dilated, damaged tubules)

18. ATN Causes Hypotension Post-op Ischemia
Relative low BP
May occur immediately after low BP episode or up to 7 days later
Post-op Ischemia
Post-aortic clamping, post-CABG
Crystal precipitation
Myoglobinuria
Contrast Dye
ARF usually 1-2 days after IV contrast load
Aminoglycosides

19. ATN Treatment Remove any offending agent
IVF
Try Lasix if a euvolemic patient is not having adequate urine output
Dialysis
Most patients return to baseline Serum Cr in 7 to 21 days

20. ATN
Prerenal Cr
increases at /day
increases slower than 0.3 /day
U Na, FeNa
UNa>40
FeNa >2%
UNa<20
FeNa<1% UA
epithelial cells, granular casts
Normal
Response to volume
Cr will not improve much
Cr improves with IVF
BUN/Cr
10-15:1
>20:1

21. Which UA is most compatible with contrast-induced ATN?
Spec gravity 1.012, RBC, WBC, positive for eosinophils
Spec gravity 1.010, 1-3 WBC, 5-10 renal tubular cells, many granular casts, occasional renal tubular cell casts, no eosinophils
Spec gravity 1.012, 5-10 RBC, WBC, many bacteria, occasional fine granular casts, no eosinophils
Spec gravity 1.020, RBC, 2-4 WBC, 1-3 RBC casts, no eosinophils

22. ATN
B. Spec gravity 1.010, 1-3 WBC, 5-10 renal tubular cells, many granular casts, occasional renal tubular cell casts, no eosinophils
Dilute urine: failure to concentrate urine
No RBC casts or WBC casts in ATN
Eosinophils classically in AIN or renal atheroemboli, but nonspecific

23. WBC Casts Cells in the cast have nuclei (unlike RBC casts)
Pathognomonic for Acute Interstitial Nephritis

24. Acute Interstitial Nephritis
70% Drug hypersensitivity
30% Antibiotics: PCN, Cephalosporins, Cipro
Sulfa drugs
NSAIDs
Allopurinol
15% Infection
Strep, Legionella, CMV
8% Idiopathic
6% Autoimmune Diseases
Sarcoid, Tubulointerstitial nephritis

25. AIN from Drugs Renal damage is NOT dose-dependent
May take weeks after initial exposure to drug
Up to 18 months to get AIN from NSAIDS
But only 3-5 days to develop AIN after second exposure to drug
Signs and Symtpoms
Fever (27%)
Serum Eosinophilia (23%)
Maculopapular rash (15%)
Labs
Bland sediment or WBCs, RBCs, non-nephrotic proteinuria
WBC Casts are pathognomonic
Urine eosinophils on Wright’s or Hansel’s Stain
Also see urine eosinophils in RPGN and renal atheroemboli

26. AIN Management Remove offending agent
Most patients recover full kidney function in 1 year
Poor prognostic factors
ARF > 3 weeks
Advanced age at onset

27. Acute glomerulonephritis Acute interstitial nephritis
You evaluate a 32yo woman with HTN, oliguria, and rapidly increasing Cr, BUN. You spin her urine:
ATN
Acute glomerulonephritis
Acute interstitial nephritis
Nephrotic Syndrome
RBC casts

28. Acute Glomerulonephritis
RBC casts: cells have no nuclei
Casts in urine: think INTRINSIC renal disease
If she has Lupus with recent viral prodrome, think Rapidly Progressive Glomerulonephritis (RPGN)
If she had a sore throat 10 days ago, think Postinfectious Proliferative Glomerulonephritis

29. Glomerular Disease Hematuria: dysmorphic RBCs RBC casts
Lipiduria: increased glomerular permeability
Proteinuria: may be in nephrotic range
Fever, rash, arthralgias, pulmonary symptoms
Elevated ESR, low complement levels

30. Rapidly Progressive Glomerulonephritis
Type 1: Anti-GBM disease
Type 2: Immune complex
IgA nephropathy
Postinfectious glomerulonephritis
Lupus nephritis
Mixed cryoglobulinemia
Type 3: Pauci-immune
Necrotizing glomerulonephritis
Often ANCA-positive and associated with vasculitis
Can present with viral-like prodrome
Myalgias, arthralgias, back pain, fever, malaise
Kidney biopsy : Extensive cellular crescents with or without immune complexes
Can develop ESRD in days to weeks
Treat with glucocorticoids and cyclophosphamide

31. Postinfectious Proliferative Glomerulonephritis
Usually after strep infection of upper respiratory tract or skin after a 8-14 day latent period
Can also occur in subacute bacterial endocarditis, visceral abscesses, osteomyelitis, bacterial sepsis
Hematuria, hypertension, edema, proteinuria
Positive antistreptolysin O titer (90% upper respiratory and 50% skin)
Treatment is supportive
Screen family members with throat culture and treat with antibiotics if necessary

32. A 19yo woman with Breast Cancer s/p chemo in the ER has weakness, fever, rash. WBC=15.4, Hct 24, Cr 2.9, LDH 600, CK UA=3+ protein, 3+blood, 20 RBC. What next test do you order? What’s her likely diagnosis?
Nephrotic Syndrome
ATN
Acute Glomerulonephritis
Thrombotic Thromboctyopenic Purpura
Rhabdomyolysis

33. TTP Order blood smear to rule out TTP
TTP associated with malignancy and chemotherapy
TTP may mimic Glomerulonephritis on UA (RBCs, WBCs)
Thrombocytopenia and anemia not consistent with nephrotic or nephritic syndrome
Need CK in the thousands to cause ARF

34. Microvascular ARF TTP/HUS HELLP syndrome
Platelets form thrombi and deposit in kidneys leading to glomerular capillary occlusion or thrombosis
Plasma exchange, steroids, IVIG, and splenectomy are possible treatments

35. Macrovascular ARF Aortic Aneurysm
Renal artery dissection or thrombosis
Renal vein thrombus
Atheroembolic disease
New onset or accelerated HTN?
Abdominal bruits, reduced femoral pulses?
Vascular disease?
Embolic source?

36. Your 68yo male inpatient with baseline Cr=1
Your 68yo male inpatient with baseline Cr=1.2 had negative cardiac cath 4 days ago, now Cr=1.8 and blanching rash.
Renal Artery Stenosis
Contrast-Induced Nephropathy
C. Abdominal Aortic Aneurysm
D. Cholesterol Atheroemboli

37. Why do his toes look like this?

38. Renal Atheroembolic Disease
1% of cardiac caths can cause atheromatous debris scraped from the aortic wall will embolize
Retinal
Cerebral
Skin (Livedo Reticularis, Purple toes)
Renal (ARF)
Gut (Mesenteric ischemia)
Unlike in Contrast-Induced Nephropathy, Serum Cr will NOT improve with IVF
Diagnosis of exclusion: will NOT show up on MRI or Renal U/S; WILL show up on renal biopsy
Treatment is supportive

39. Post-Renal ARF Urethral obstruction: prostate or urethral stricture
Bladder calculi or neoplasm
Pelvic or retroperitoneal neoplams
Bilateral ureteral obstruction
Retroperitoneal fibrosis

40. “Doc, your patient has not peed in 5 hrs....what do you want to do?”
Examine patient: Dry? Septic?
Flush foley: sediment can obstruct outflow
Check I/Os: Has she been drinking?
Give IV BOLUS ( cc IVF), see if patient has urine output in next min
If yes, then patient was dry
If no, then patient is either REALLY dry or in renal failure
Check UA, Labs
Consider Renal U/S if reasonable

41. You are called to the ER to see...
A 35yo woman with previously normal renal function now with BUN=60, Cr=3.5. Do you call the Renal fellow to dialyze this pt?
What if her K=5.9?
What if her K=7.8?

42. Indications for acute dialysis
AEIOU
Acidosis (metabolic)
Electrolytes (hyperkalemia)
Ingestion of drugs/Ischemia
Overload (fluid)
Uremia

43. You admit this patient to telemetry and aggressively hydrate her
You recheck labs 6h later and BUN=85, Cr=4.2. Suddenly the patient starts to seize.
Now what?

44. Patient is Uremic General Mental status change GI disturbance
Fatigue, weakness
Pruritis
Mental status change
Uremic encephalopathy
Seizures
Asterixis
GI disturbance
Anorexia, early satiety, nausea and emesis
Uremic Pericarditis
Platlet dysfunction and bleeding

45. A patient with chronic lung disease has acute pleuritic pain and O2 saturation of 87%. You want to rule out PE but her Cr is Can you get a CT with IV contrast?
Send her for Stat CT with IV contrast
Send her for Stat CT without IV contrast
C. Just give her heparin
Begin IV hydration
Begin pre-procedure Mannitol
Get a VQ scan instead

46. Contrast-Induced Nephrotoxicity
Cr increases by 25% post-procedure
Contrast causes renal vasoconstriction leading to renal hypoxia
Iodine itself may be nephrotoxic
If Cr>1.4, use pre-procedure prophylaxis

47. Pre-Procedure Prophylaxis
IVF 0.9NS
1-1.5 mg/kg/hour x 12 hours prior to procedure and 6-12 hours after
Mucomyst (N-acetylcysteine)
Free radical scavenger; prevents oxidative tissue damage
600mg po BID x 4 doses (2 before procedure, 2 after)
Bicarbonate (JAMA 2004)
Alkalinizing urine should reduce renal medullary damage
D5W with 3 amps HCO3; bolus 3.5 mL/kg 1 hour preprocedure, then 1mL/kg/hour for 6 hours postprocedure
Small study and not reduplicated in larger trial thereafter

48. Chronic Renal Failure Definitions
Chronic Renal Failure (CRF) - irreversible kidney dysfunction with azotemia >3 months
Creatinine Clearance (CCr) - the rate of filtration of creatinine by the kidney (GFR marker)
Glomerular Filtration Rate (GFR) - the total rate of filtration of blood by the kidney

50. Etiology
Episodes of ARF (usually acute tubular necrosis) often lead, eventually, to CRF
Over time, combinations of acute renal insults are additive and lead to CRF
The definition of CRF requires that at least 3 months of renal failure have occurred
Causes of Acute Renal Failure (ARF)
Prerenal azotemia - renal hypoperfusion, usually with acute tubular necrosis
Intrinsic Renal Disease, usually glomerular disease
Postrenal azotemia - obstruction of some type

52. Common Underlying Causes of CRF
There are about 50,000 cases of ESRD per year
Diabetes: most common cause ESRD
Over 30% cases ESRD are primarily to diabetes
CRF associated HTN causes about 23% ESRD cases
Glomerulonephritis accounts for ~10% cases
Polycystic Kidney Disease - about 5% of cases
Rapidly progressive glomerulonephritis (vasculitis) - about 2% of cases
Renal (glomerular) deposition diseases
Renal Vascular Disease - renal artery stenosis, atherosclerotic vs. fibromuscular

53. Causes of CRF Additional Causes of CRF
Medications - especially causing tubulointerstitial diseases (common ARF, rare CRF)
Analgesic Nephropathy over many years
Pregnancy - high incidence of increased creatinine and HTN during pregnancy in CRF

54. Analgesic Nephropathy
Slow progression of disease due to chronic daily ingestion of analgesics
Drugs associated with this entity usually contain two antipyretic agents and either caffeine or codeine
More common in Europe and Australia than USA
Polyuria is most common earliest symptom
Macroscopic hematuria and papillary necrosis
Chronic interstitial nephritis, renal papillary necrosis, renal calcifications
Associated with long-term use of non-steroid anti-inflammatory drugs

55. Analgesic Nephropathy
Patients at risk include DM, CHF, Hepatic disease, and the elderly
Pathophysiology: nonselective NSAIDS inhibit synthesis vasodilatory prostaglandin in the kidney inducing a prerenal state ARF

56. Electrolyte Abnormalities
Excretion of sodium is initially increased, probably due to natriuretic factors
As glomerular filtration rate (GFR) falls, FeNa rises
Maintain urine volume until GFR <10-20mL/min and then edema begins
Cannot conserve sodium when GFR <25mL/min, and FeNa rises with falling GFR
Tubular potassium secretion is decreased
Cannot handle bolus potassium
Do not use potassium sparing diuretics

57. Acid Base Balance Normally, produce ~1mEq/kg/day of Hydrogen ions
When GFR <40mL/min, there is a decrease in NH4 excretion which adds to metabolic acidosis
When GFR <30mL/min, then urinary phosphate buffers decline and acidosis worsens
Bone CaCO3 begins to act as the buffer and bone lesions result (renal osteodystrophy)
Usually will not have wide anion gap acidosis if patient can still make urine
Defect in renal generation of HCO3 as well as retention of nonvolatile acids

58. Bone Metabolism
Low GFR leads to increased phosphate, low calcium, and an acidosis
Other defects include decreased dihydroxy-vitamin D production
Bone acts as a buffer for acidosis, leading to chronic bone loss in renal failure
Low vitamin D causes poor calcium absorption and secondary hyperparathyroidism
Increased PTH maintains normal serum Calcium and Phosphorus until GFR <30mL/min
Chronic hyperparathyroidism and bone buffering of acids leads to severe osteoporosis

59. Other Abnormalities
Slight hypermagnesemia with inability to excrete high magnesium loads
Uric acid retention occurs with GFR <40mL/min
Vitamin D conversion to dihydroxy-Vitamin D is severely decreased
Erythropoietin (EPO) levels fall and anemia develops
Accumulation of normally excreted substances

60. Complications Immunosuppression
Patients with CRF are at increased risk for infection
Cell mediated immunity is particularly impaired
Hemodialysis seems to increase immune compromise
Complement system is activated during hemodialysis
Patients with CRF should be vaccinated aggressively

61. Anemia Due to reduced erythropoietin production by kidney
Occurs when creatinine rises to >2.5-3mg/dL
Anemia management with Procrit and Arensp

62. Phosphorus Hyperphosphatemia Decreased excretion by kidney
Increased phosphate load from bone metabolism
Increased PTH levels leads to renal bone disease
Eventually, parathyroid gland hyperplasia occurs
Danger of calciphylaxis

63. Treatment PREVENTION Treat the underlying cause
Chronic Hemodialysis Medications
Anti-hypertensives - Labetolol, CCB, ACE inhibitors
Eythropoietin (Epogen®) for anemia in ~80% dialysis pts
Vitamin D Analogs - calcitriol given intravenously
Calcium carbonate
RenaGel, a non-adsorbed phosphate binder
DDAVP may be effective for patients with symptomatic platelet problems