1. Acute Renal Failure A. Symptoms Polyuria, Oliguria or Anuria hematuria
Dysuria
Uremia
Definition: symptomatic azotemia
Acidosis (± tachypnea)
Mental Status changes
Hypervolemia / Hypertension
Hyperkalemia
Pericarditis

2. ------------------------ Serum Cr x 72
Duration <3 months
Oliguria <400 ml urine/24 hours
Absolute increase Scr by 0.5 or 1.0 mg/dl or relative increase 25%
Cockcroft – Gault Equation
(140-age) x wt(kg)
Serum Cr x 72

3. B. Etiologies
Location of Lesion
Prerenal - ~70% of cases
Intrinsic - ~25% of cases
Post-renal (obstructive) - <5% of cases
FeNa= urine Na x serum Cr
X 100
serum Na x urine Cr
Prerenal Renal (ATN)
Urine Na <10 >10
FeNa <1% >1%
response IVF good poor
BUN/Scr >20 nl

4. Decreased effective arterial volume
Pre-renal azotemia
Decreased effective arterial volume
CHF,,Cirrhosis,,Nephrotic syndrome,,Sepsis
Renal Artery Stenosis (atherosclerosis, fibromuscular dysplasia)
Cardiopulmonary bypass (>3 hours)
Intravascular volume depletion
GI loss…Vomiting..diarrhea…etc
Renal loss diuretc..osmotic diuresis..etc
Cutaneous loss hyperthermia..burns
Hemorrhage
Third space pancreatitis..severe hypoalbuminemia..cappillary leak

5. II.Parenchymal Damage
Nephritis (inflammation): glomerular vs. interstitial
Tubular Injury: most common cause of ARF Nephrotic Syndrome (total protein losses)
III. Obstruction of Outflow (~5%) Urinary Tract Infection (UTI) with Pyelonephritis
Urinary Calculus disease (renal stones)
Crystal Deposition
Bladder tumors with extensive invasion
Prostatic Enlargement: BPH vs. Carcinoma
Unilateral obstruction with only one functioning kidney

6. Vascular hypertension
Atherosclerotic (atheroembolism) - cholesterol emboli, 5-10% of hospitalized ARF Trauma
Vasculitides
Post-operative - aortic aneurysm repair, aortic cross-clamping
Vasoconstricting Agents - NSAIDs, vasopressors

7. Drug Induced
ACE Inhibitors
Radiocontrast Dye Interstitial Nephritis - sulfonamides, NSAIDS, other antibiotics
Amphotericin
Cis-Platinum
Aminoglycosides
Non-steroidal anti-inflammatory drugs (NSAIDs)

8. Pathophysiology
Ischemia is the underlying problem in ARF
leads to depletion of cellular ATP and release of calcium
Reactive oxygen species produced leading to further cell death
Calcium release leads to phospholipase activation
Neutrophils may mediate reperfusion injury (ICAM-1 is involved)
Many nephrotoxins are renal vasocontrictors (eg. cyclosporine, radiocontrast)

9. C. Initial Evaluation
Consider possible etiologies and direct evaluation
Medications should always be suspected
Standard Blood Testing
Electrolyte/renal panel, Ca2+, Phosphate, Mg2+, Albumin
Complete Blood Count
Foley catheter to rule out bladder obstruction

10. Urine for electrolytes, dipstick and microscopic analysis
Osmolality, creatinine, Na+, K+, Cl-
Urine spot protein to creatinine ratio (normal is <0.2)
Pigment: Hemoglobin (myoglobin)
Cells, Casts, Crystals, Organisms
Consider Urine culture

11. Renal/Pelvic Sono - stones, hydronephrosis, mass
Consider Abdominal radiograph if ultrasound is not done to rule out stones
ESR, ASO titer, ANA, C3/C4 Anti-GBM Abs
Renal Biopsy in rapidly progressing disease
ANCA and Anti-GBM diseases - consider cyclophosphamide + glucocorticoids
Idiopathic rapidly progressive glomerulonephritis often ANCA positive (other inflammatory diseases such as bacterial endocarditis can given ANCA+)

12. Pathology Summary
Glomerular Involvement
Diffuse: all glomeruli in a section are diseased
Focal: some glomeruli in a section are diseased
Segmental: parts of individual glomerulus affected
2.Focal Glomerulonephritis:
Some glomeruli are dead( necrosis, collapse, sclerosis
b.Acute or chronic inflamation is often seen
3.Crescent Glomerulonephritis (very poor prognosis)
Crescent (moon shaped) formation in glomerulus
Affected glomeruli are non-functional

13. Focal and Segmental Glomerulosclerosis: portions of many glomeruli are destroyed
5. Minimal Change Glomerulonephritis
a. Glomeruli appear okay, but function is poor
b. Electron microscopic evidence of basement membrane disease
c. Response to glucocorticoids is usually very good
6. IgA Deposition
a.IgA nephropathy
b.Deposition of IgA immune complexes
c.Differential includes Systemic Lupus (SLE) and Henoch-Schonlein Purpura (HSP)

14. 7. Proliferative Glomerulonephritis
a. Increase in mesangeal cell number
b. Usually follows insults (eg. Post-Streptococcal)
May be seen in collagen vascular disease, SLE
8. Collapsing Glomerulonephritis
Major form seen in HIV nephropathy
Usually late stage
Rapid progression to renal failure (weeks-months)
No effective therapy to date

15. 9. Tubular Necrosis
a. Tubular cells die and slough off basement membrane
b. The dead tubular cells form casts which can occlude lumen
c. Glomular basement membrane may also be damaged

16. E. Management
Renal Diet
Low phosphate, potassium, sodium, and protein
High calcium and vitamin D
Various multivitamin formulas available for renal patients, eg. Nephrovit®
Low protein diet may slow progression slightly in chronic renal disease
Phosphate and Calcium
Dangerous if product of Calcium and Phosphage > ~70 (mg/dl) (will lead to precipitation)

17. If product is close to 70, then phosphate should be lowered with aluminum compounds
These compounds should be given with meals to bind the phosphate directly
If product is <60, then calcium should be given mg po tid with meals
If calcium is low but phosphate normal, then calcium should be given before meals
Consider using 1,25 dihyroxyvitamin D supplements

18. 1. Acidosis
Renal tublar acidosis (RTA) is common in early renal failure
Oral bicitra (citrate replaces bicarbonate) may be used
Bicitra is contraindicated in edematous states due to high sodium content
2. Hyperuricemia
Check uric acid levels
Uric acid deposition in renal tubules may worsen progression of renal failure
Allopurinol may be given ( mg po qd) to attempt normalization of uric acid

19. 3. Hypertension
a. ACE inhibitors generally contraindicated in moderate to severe renal failure
Calcium blockers such as nifedipine
Labetolol is also very effective but patient should have LV EF>50% and no bronchospasm
d. Consider Hydralazine for afterload reduction
e. Pure alpha-adrenergic blocking agents may be effective, but tachyphylaxis may occur
Diuretic improve hypertension/ volume overload

20. 4. Volume overload
a. Attempt to maximize cardiac output and improve intravascular volume
b. Diuretics often worsen renal failure but may be necessary to prevent pulmonary edema
c. In general, potassium sparing diuretics should be avoided (high risk hyperkalemia)
e. Dopamine or mannitol can be tried, but are usually not effective
f. Albumin infusions are probably not helpful, but may help diuresis in low albumin states
g. Dialysis may be required particularly in severe volume overload situations

21. 5. Protein Load
Reducing protein load is thought to reduce azotemia
Appears to slow progression of CRF
Patients with moderate renal disease - some decrease in progression on low protein diet
Patients with severe renal disease show no benefit on low protein diet
6. Hospital inpatients with ARF ~50% mortality rate

22. 7. Newer Agents
Atrial natriuretic factor (ANF)= dilators + diuretic
ANF (Auriculin®) ? efficacy in oliguric ARF
ANF may increase renal dysfunction in diabetics receiving radiocontrast
Brain derived natriuretic factor (BDNF) may be effective some patients
Other vasodilators (eg. calcium channel blockers) are not effective
Investigation renal growth/regeneration factors

23. 8. Dialysis Indications
Serum abnormalities unresponsive to medical therapy
Severe Acidosis
Severe Hyperkalemia
II Uremia
Mental status changes (usually delirium)
Nausea and vomiting
Pericarditis (pericardial friction rub)

24. III Volume Overload
Hemofiltration or hemodialysis can be used to allow recovery of kidney after ARF
Average duration of need for these therapies was 9 days in ARF
After this time, kidneys regain function and increase urine output
Native kidneys may continue with minimal function for 6-12 months of hemodialysis
After that, native kidneys usually shut down permanently

25. Kidney Transplantation
Excellent (and improving) results with cadaveric grafts.
Living Related Donor kidneys superior to CRT
New kidney usually placed in extraperitoneally in the pelvis
Cyclosporin ,Prednisone, OKT3, mycophenolic acid, FK506 immunosuppression
Combined Kidney Pancreas transplant in Diabetic ESRD patients