Acute Renal FailureAcute Renal Failure

A. Symptoms A. Symptoms

1.1.Polyuria, Oliguria or Anuria hematuria Polyuria, Oliguria or Anuria hematuria

2.2.Dysuria Dysuria

3.3.Uremia Uremia

a.a.Definition: symptomatic azotemia Definition: symptomatic azotemia

b.b.Acidosis (± tachypnea) Acidosis (± tachypnea)

c.c.Mental Status changes Mental Status changes

d.d.Hypervolemia / Hypertension Hypervolemia / Hypertension

e.e.Hyperkalemia Hyperkalemia

f.f. PericarditisPericarditis

1.1. Duration <3 monthsDuration <3 months

2.2. Oliguria <400 ml urine/24 hoursOliguria <400 ml urine/24 hours

3.3. Absolute increase Scr by 0.5 or 1.0 mg/dl or Absolute increase Scr by 0.5 or 1.0 mg/dl or relative increase 25%relative increase 25%

4.4. Cockcroft – Gault EquationCockcroft – Gault Equation

(140-age) x wt(kg)(140-age) x wt(kg)

------------------------------------------------

Serum Cr x 72Serum Cr x 72

B. Etiologies B. Etiologies 1.1. Location of Lesion Location of Lesion a.a. Prerenal - ~70% of cases Prerenal - ~70% of cases b.b. Intrinsic - ~25% of cases Intrinsic - ~25% of cases c.c. Post-renal (obstructive) - <5% of casesPost-renal (obstructive) - <5% of casesd.d. FeNa= urine Na x serum CrFeNa= urine Na x serum Cr

-------------------------------------------------------------- X 100X 100 serum Na x urine Crserum Na x urine Cr

PrerenalPrerenal Renal (ATN)Renal (ATN)Urine Na Urine Na <10<10 >10>10 FeNa FeNa <1%<1% >1%>1%response IVFresponse IVF goodgood poorpoorBUN/ScrBUN/Scr >20>20 nlnl

1.1. Pre-renal azotemia Pre-renal azotemia

Decreased effective arterial volumeDecreased effective arterial volume- CHF,,Cirrhosis,,Nephrotic syndrome,,SepsisCHF,,Cirrhosis,,Nephrotic syndrome,,Sepsis- Renal Artery Stenosis (atherosclerosis, Renal Artery Stenosis (atherosclerosis,

fibromuscular dysplasia) fibromuscular dysplasia) - Cardiopulmonary bypass (>3 hours)Cardiopulmonary bypass (>3 hours)

Intravascular volume depletionIntravascular volume depletion– GI loss…Vomiting..diarrhea…etcGI loss…Vomiting..diarrhea…etc– Renal loss diuretc..osmotic diuresis..etcRenal loss diuretc..osmotic diuresis..etc– Cutaneous loss hyperthermia..burnsCutaneous loss hyperthermia..burns– HemorrhageHemorrhage– Third space pancreatitis..severe Third space pancreatitis..severe

hypoalbuminemia..cappillary leakhypoalbuminemia..cappillary leak

II.Parenchymal Damage II.Parenchymal Damage • Nephritis (inflammation): glomerular vs. Nephritis (inflammation): glomerular vs.

interstitial interstitial • Tubular Injury: most common cause of ARF Tubular Injury: most common cause of ARF

Nephrotic Syndrome (total protein losses) Nephrotic Syndrome (total protein losses)

III. Obstruction of Outflow (~5%) Urinary Tract III. Obstruction of Outflow (~5%) Urinary Tract Infection (UTI) with Pyelonephritis Infection (UTI) with Pyelonephritis

a.a. Urinary Calculus disease (renal stones) Urinary Calculus disease (renal stones) b.b. Crystal Deposition Crystal Deposition c.c. Bladder tumors with extensive invasion Bladder tumors with extensive invasion d.d. Prostatic Enlargement: BPH vs. Carcinoma Prostatic Enlargement: BPH vs. Carcinoma e.e. Unilateral obstruction with only one Unilateral obstruction with only one

functioning kidney functioning kidney

1.1. Vascular hypertension Vascular hypertension a.a. Atherosclerotic (atheroembolism) - cholesterol Atherosclerotic (atheroembolism) - cholesterol

emboli, 5-10% of hospitalized ARF Trauma emboli, 5-10% of hospitalized ARF Trauma b.b. Vasculitides Vasculitides c.c. Post-operative - aortic aneurysm repair, aortic Post-operative - aortic aneurysm repair, aortic

cross-clamping cross-clamping d.d. Vasoconstricting Agents - NSAIDs, Vasoconstricting Agents - NSAIDs,

vasopressors vasopressors

1.1. Drug Induced Drug Induced

a.a. ACE Inhibitors ACE Inhibitors

b.b. Radiocontrast Dye Interstitial Nephritis Radiocontrast Dye Interstitial Nephritis - sulfonamides, NSAIDS, other - sulfonamides, NSAIDS, other antibiotics antibiotics

c.c. Amphotericin Amphotericin

d.d. Cis-Platinum Cis-Platinum

e.e. Aminoglycosides Aminoglycosides

f.f. Non-steroidal anti-inflammatory drugs Non-steroidal anti-inflammatory drugs (NSAIDs) (NSAIDs)

1.1. Pathophysiology Pathophysiology 2.2. Ischemia is the underlying problem in ARF Ischemia is the underlying problem in ARF a.a. leads to depletion of cellular ATP and release of leads to depletion of cellular ATP and release of

calcium calcium b.b. Reactive oxygen species produced leading to further Reactive oxygen species produced leading to further

cell death cell death c.c. Calcium release leads to phospholipase activation Calcium release leads to phospholipase activation d.d. Neutrophils may mediate reperfusion injury (ICAM-1 is Neutrophils may mediate reperfusion injury (ICAM-1 is

involved) involved) e.e. Many nephrotoxins are renal vasocontrictors (eg. Many nephrotoxins are renal vasocontrictors (eg.

cyclosporine, radiocontrast)cyclosporine, radiocontrast)

C. Initial Evaluation C. Initial Evaluation 1.1. Consider possible etiologies and direct Consider possible etiologies and direct

evaluation evaluation 2.2. Medications should always be suspected Medications should always be suspected 3.3. Standard Blood Testing Standard Blood Testing a.a. Electrolyte/renal panel, Ca2+, Phosphate, Electrolyte/renal panel, Ca2+, Phosphate,

Mg2+, Albumin Mg2+, Albumin b.b. Complete Blood Count Complete Blood Count c.c. Foley catheter to rule out bladder Foley catheter to rule out bladder

obstructionobstruction

1.1. Urine for electrolytes, dipstick and Urine for electrolytes, dipstick and microscopic analysis microscopic analysis

a.a. Osmolality, creatinine, Na+, K+, Cl- Osmolality, creatinine, Na+, K+, Cl-

b.b. Urine spot protein to creatinine ratio Urine spot protein to creatinine ratio (normal is <0.2) (normal is <0.2)

c.c. Pigment: Hemoglobin (myoglobin) Pigment: Hemoglobin (myoglobin)

d.d. Cells, Casts, Crystals, Organisms Cells, Casts, Crystals, Organisms

e.e. Consider Urine culture Consider Urine culture

1.1. Renal/Pelvic Sono - stones, hydronephrosis, Renal/Pelvic Sono - stones, hydronephrosis, mass mass

2.2. Consider Abdominal radiograph if ultrasound is Consider Abdominal radiograph if ultrasound is not done to rule out stones not done to rule out stones

3.3. ESR, ASO titer, ANA, C3/C4 Anti-GBM Abs ESR, ASO titer, ANA, C3/C4 Anti-GBM Abs 4.4. Renal Biopsy in rapidly progressing disease Renal Biopsy in rapidly progressing disease a.a. ANCA and Anti-GBM diseases - consider ANCA and Anti-GBM diseases - consider

cyclophosphamide + glucocorticoids cyclophosphamide + glucocorticoids b.b. Idiopathic rapidly progressive glomerulonephritis Idiopathic rapidly progressive glomerulonephritis

often ANCA positive (other inflammatory often ANCA positive (other inflammatory diseases such as bacterial endocarditis can diseases such as bacterial endocarditis can given ANCA+)given ANCA+)

Pathology SummaryPathology Summary

1.1. Glomerular Involvement Glomerular Involvement

a.a. Diffuse: all glomeruli in a section are diseased Diffuse: all glomeruli in a section are diseased

b.b. Focal: some glomeruli in a section are diseased Focal: some glomeruli in a section are diseased

c.c. Segmental: parts of individual glomerulus affectedSegmental: parts of individual glomerulus affected

2.Focal Glomerulonephritis: 2.Focal Glomerulonephritis:

a.a. Some glomeruli are dead( necrosis, collapse, sclerosis Some glomeruli are dead( necrosis, collapse, sclerosis

b.Acute or chronic inflamation is often seen b.Acute or chronic inflamation is often seen

3.Crescent Glomerulonephritis (very poor prognosis) 3.Crescent Glomerulonephritis (very poor prognosis)

a.a. Crescent (moon shaped) formation in glomerulus Crescent (moon shaped) formation in glomerulus

b.b. Affected glomeruli are non-functionalAffected glomeruli are non-functional

4.4. Focal and Segmental Glomerulosclerosis: portions Focal and Segmental Glomerulosclerosis: portions of many glomeruli are destroyed of many glomeruli are destroyed

5.5. Minimal Change Glomerulonephritis Minimal Change Glomerulonephritis a.a. Glomeruli appear okay, but function is poor Glomeruli appear okay, but function is poor b.b. Electron microscopic evidence of basement Electron microscopic evidence of basement

membrane disease membrane disease c.c. Response to glucocorticoids is usually very goodResponse to glucocorticoids is usually very good 6.6. IgA Deposition IgA Deposition a.IgA nephropathy a.IgA nephropathy b.Deposition of IgA immune complexes b.Deposition of IgA immune complexes c.Differential includes Systemic Lupus (SLE) and c.Differential includes Systemic Lupus (SLE) and

Henoch-Schonlein Purpura (HSP) Henoch-Schonlein Purpura (HSP)

7.7. Proliferative Glomerulonephritis Proliferative Glomerulonephritis a.a. Increase in mesangeal cell number Increase in mesangeal cell number b.b. Usually follows insults (eg. Post-Usually follows insults (eg. Post-

Streptococcal) Streptococcal) c.c. May be seen in collagen vascular disease, May be seen in collagen vascular disease,

SLESLE

8.8. Collapsing Glomerulonephritis Collapsing Glomerulonephritis a.a. Major form seen in HIV nephropathy Major form seen in HIV nephropathy b.b. Usually late stage Usually late stage c.c. Rapid progression to renal failure (weeks-Rapid progression to renal failure (weeks-

months) months) d.d. No effective therapy to date No effective therapy to date

9.9.Tubular Necrosis Tubular Necrosis

a.a.Tubular cells die and slough off basement Tubular cells die and slough off basement membrane membrane

b.b.The dead tubular cells form casts which The dead tubular cells form casts which can occlude lumen can occlude lumen

c.c.Glomular basement membrane may also Glomular basement membrane may also be damaged be damaged

E. Management E. Management

Renal Diet Renal Diet a.a. Low phosphate, potassium, sodium, and Low phosphate, potassium, sodium, and

protein protein b.b. High calcium and vitamin D High calcium and vitamin D c.c. Various multivitamin formulas available for Various multivitamin formulas available for

renal patients, eg. Nephrovit® renal patients, eg. Nephrovit® d.d. Low protein diet may slow progression slightly Low protein diet may slow progression slightly

in chronic renal disease in chronic renal disease e.e. Phosphate and Calcium Phosphate and Calcium f.f. Dangerous if product of Calcium and Dangerous if product of Calcium and

Phosphage > ~70 (mg/dl) (will lead to Phosphage > ~70 (mg/dl) (will lead to precipitation) precipitation)

a.a. If product is close to 70, then phosphate If product is close to 70, then phosphate should be lowered with aluminum should be lowered with aluminum compounds compounds

b.b. These compounds should be given with These compounds should be given with meals to bind the phosphate directly meals to bind the phosphate directly

c.c. If product is <60, then calcium should be If product is <60, then calcium should be given 500-1000mg po tid with meals given 500-1000mg po tid with meals

d.d. If calcium is low but phosphate normal, then If calcium is low but phosphate normal, then calcium should be given before meals calcium should be given before meals

e.e. Consider using 1,25 dihyroxyvitamin D Consider using 1,25 dihyroxyvitamin D supplements supplements

1.1. Acidosis Acidosis Renal tublar acidosis (RTA) is common in Renal tublar acidosis (RTA) is common in early renal failure early renal failure Oral bicitra (citrate replaces bicarbonate) Oral bicitra (citrate replaces bicarbonate) may be used may be used Bicitra is contraindicated in edematous Bicitra is contraindicated in edematous states due to high sodium content states due to high sodium content

2.2. Hyperuricemia Hyperuricemia Check uric acid levels Check uric acid levels Uric acid deposition in renal tubules may Uric acid deposition in renal tubules may worsen progression of renal failure worsen progression of renal failure Allopurinol may be given (100-200mg po Allopurinol may be given (100-200mg po qd) to attempt normalization of uric acidqd) to attempt normalization of uric acid

3.3. Hypertension Hypertension

a.a. ACE inhibitors generally contraindicated in ACE inhibitors generally contraindicated in moderate to severe renal failure moderate to severe renal failure

b.b. Calcium blockers such as nifedipine Calcium blockers such as nifedipine

c.c. Labetolol is also very effective but patient Labetolol is also very effective but patient should have LV EF>50% and no should have LV EF>50% and no bronchospasm bronchospasm

d.d. Consider Hydralazine for afterload reduction Consider Hydralazine for afterload reduction

e.e. Pure alpha-adrenergic blocking agents may Pure alpha-adrenergic blocking agents may be effective, but tachyphylaxis may occur be effective, but tachyphylaxis may occur

f.f. Diuretic improve hypertension/ volume Diuretic improve hypertension/ volume overload overload

4.4. Volume overload Volume overload a.a. Attempt to maximize cardiac output and Attempt to maximize cardiac output and

improve intravascular volume improve intravascular volume b.b. Diuretics often worsen renal failure but may Diuretics often worsen renal failure but may

be necessary to prevent pulmonary edema be necessary to prevent pulmonary edema c.c. In general, potassium sparing diuretics In general, potassium sparing diuretics

should be avoided (high risk hyperkalemia) should be avoided (high risk hyperkalemia) e.e. Dopamine or mannitol can be tried, but are Dopamine or mannitol can be tried, but are

usually not effective usually not effective f.f. Albumin infusions are probably not helpful, Albumin infusions are probably not helpful,

but may help diuresis in low albumin states but may help diuresis in low albumin states g.g. Dialysis may be required particularly in Dialysis may be required particularly in

severe volume overload situations severe volume overload situations

5.5. Protein Load Protein Load

a.a. Reducing protein load is thought to reduce Reducing protein load is thought to reduce azotemia azotemia

b.b. Appears to slow progression of CRFAppears to slow progression of CRFc.c. Patients with moderate renal disease - some Patients with moderate renal disease - some

decrease in progression on low protein diet decrease in progression on low protein diet d.d. Patients with severe renal disease show no Patients with severe renal disease show no

benefit on low protein diet benefit on low protein diet

6.6. Hospital inpatients with ARF ~50% mortality Hospital inpatients with ARF ~50% mortality raterate

7.7. Newer Agents Newer Agents a.a. Atrial natriuretic factor (ANF)= dilators + Atrial natriuretic factor (ANF)= dilators +

diuretic diuretic b.b. ANF (Auriculin®) ? efficacy in oliguric ARFANF (Auriculin®) ? efficacy in oliguric ARFc.c. ANF may increase renal dysfunction in ANF may increase renal dysfunction in

diabetics receiving radiocontrast diabetics receiving radiocontrast d.d. Brain derived natriuretic factor (BDNF) may Brain derived natriuretic factor (BDNF) may

be effective some patients be effective some patients e.e. Other vasodilators (eg. calcium channel Other vasodilators (eg. calcium channel

blockers) are not effective blockers) are not effective f.f. Investigation renal growth/regeneration Investigation renal growth/regeneration

factorsfactors

8. Dialysis Indications8. Dialysis Indications1.1. Serum abnormalities unresponsive to medical Serum abnormalities unresponsive to medical

therapy therapy a.a. Severe Acidosis Severe Acidosis b.b. Severe Hyperkalemia Severe Hyperkalemia

IIII Uremia Uremia a.a. Mental status changes (usually delirium) Mental status changes (usually delirium) b.b. Nausea and vomiting Nausea and vomiting c.c. Pericarditis (pericardial friction rub) Pericarditis (pericardial friction rub)

IIIIII Volume Overload Volume Overload • Hemofiltration or hemodialysis can be used Hemofiltration or hemodialysis can be used

to allow recovery of kidney after ARF to allow recovery of kidney after ARF

a.a. Average duration of need for these Average duration of need for these therapies was 9 days in ARF therapies was 9 days in ARF

b.b. After this time, kidneys regain function and After this time, kidneys regain function and increase urine output increase urine output

c.c. Native kidneys may continue with minimal Native kidneys may continue with minimal function for 6-12 months of hemodialysis function for 6-12 months of hemodialysis

d.d. After that, native kidneys usually shut down After that, native kidneys usually shut down permanentlypermanently

Kidney Transplantation Kidney Transplantation

Excellent (and improving) results with Excellent (and improving) results with cadaveric grafts.cadaveric grafts.Living Related Donor kidneys superior to CRTLiving Related Donor kidneys superior to CRT

1.1. New kidney usually placed in New kidney usually placed in extraperitoneally in the pelvis extraperitoneally in the pelvis

2.2. Cyclosporin ,Prednisone, OKT3, Cyclosporin ,Prednisone, OKT3, mycophenolic acid, FK506 mycophenolic acid, FK506 immunosuppression immunosuppression Combined Kidney Pancreas transplant in Combined Kidney Pancreas transplant in Diabetic ESRD patientsDiabetic ESRD patients