Acute and Chronic Renal Failure

Courtney Bunevich, DO

December 19, 2007

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

DefinitionsAnuria: No urine output

Oliguria: Urine output <400-500 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 10-20 mL/min, or 20-50% of normal

ESRD: GFR <5% of normal

ARF: Signs and Symptoms

Hyperkalemia Nausea/Vomiting HTN Pulmonary edema Ascites Asterixis Encephalopathy

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

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?

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)

Workup for ARF

BMP or RFP Urine

Urine electrolytes and Urine Cr to calculate FeNa

Urine eosinophilsUrine sediment: casts, cells, proteinUosm

Kidney U/S to rule out hydronephrosis

FeNa = (urine Na x plasma Cr) (plasma Na x urine Cr)FeNa <1% 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

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

Calculating FeNa after Patient Has Recieved Lasix Caution with calculating FeNa if pt has gotten

loop diuretics in past 24-48 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%

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

Prerenal causes 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

Intrinsic ARF

1. Tubular (ATN)

2. Interstitial (AIN)

3. Glomerular (Glomerulonephritis)

4. Vascular

You evaluate a 57yo man with oliguria and rapidly increasing BUN and Serum Cr

A. ATNB. Acute glomerulonephritisC. Acute interstitial nephritisD. Nephrotic Syndrome

ATN Muddy brown granular casts (last slide) Renal tubular epithelial cell casts (below)

More ATN

•Broad casts (form in dilated, damaged tubules)

ATN Causes Hypotension

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

ATN Treatment

Remove any offending agent IVFTry Lasix if a euvolemic patient is not having

adequate urine outputDialysis

Most patients return to baseline Serum Cr in 7 to 21 days

ATN Prerenal

Cr increases at 0.3-0.5 /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

Which UA is most compatible with contrast-induced ATN?A. Spec gravity 1.012, 20-30 RBC, 15-20 WBC,

positive for eosinophilsB. Spec gravity 1.010, 1-3 WBC, 5-10 renal

tubular cells, many granular casts, occasional renal tubular cell casts, no eosinophils

C. Spec gravity 1.012, 5-10 RBC, 25-50 WBC, many bacteria, occasional fine granular casts, no eosinophils

D. Spec gravity 1.020, 10-20 RBC, 2-4 WBC, 1-3 RBC casts, no eosinophils

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

WBC Casts

Cells in the cast have nuclei(unlike RBC casts)

Pathognomonic for Acute Interstitial Nephritis

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

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

AIN Management

Remove offending agent Most patients recover full kidney function

in 1 year Poor prognostic factors

ARF > 3 weeksAdvanced age at onset

You evaluate a 32yo woman with HTN, oliguria, and rapidly increasing Cr, BUN. You spin her urine:

A. ATNB. Acute glomerulonephritisC. Acute interstitial nephritisD. Nephrotic Syndrome

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

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

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

Rapidly Progressive 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

Postinfectious Proliferative Glomerulonephritis

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 600. UA=3+ protein, 3+blood, 20 RBC. What next test do you order? What’s her likely diagnosis?

A. Nephrotic Syndrome

B. ATNC. Acute

GlomerulonephritisD. Thrombotic

Thromboctyopenic Purpura

E. Rhabdomyolysis

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

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

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?

A. Renal Artery Stenosis

B. Contrast-Induced Nephropathy

C. Abdominal Aortic Aneurysm

D. Cholesterol Atheroemboli

Your 68yo male inpatient with baseline Cr=1.2 had negative cardiac cath 4 days ago, now Cr=1.8 and blanching rash.

Why do his toes look like this?

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

Post-Renal ARF

• Urethral obstruction: prostate or urethral stricture• Bladder calculi or neoplasm• Pelvic or retroperitoneal neoplams• Bilateral ureteral obstruction• Retroperitoneal fibrosis

“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 (250-500cc IVF), see if patient has

urine output in next 30-60 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

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?

Indications for acute dialysis

AEIOUAcidosis (metabolic)Electrolytes (hyperkalemia) Ingestion of drugs/IschemiaOverload (fluid)Uremia

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?

Patient is Uremic

General Fatigue, weakness Pruritis

Mental status change Uremic encephalopathy Seizures Asterixis

GI disturbance Anorexia, early satiety, nausea and emesis

Uremic Pericarditis Platlet dysfunction and bleeding

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 1.4. Can you get a CT with IV contrast?

A. Send her for Stat CT with IV contrast

B. Send her for Stat CT without IV contrast

C. Just give her heparin

D. Begin IV hydration

E. Begin pre-procedure Mannitol

F. Get a VQ scan instead

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

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

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

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

Etiology

Common Underlying Causes of CRF 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

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

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

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

Analgesic Nephropathy

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

Electrolyte Abnormalities

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

Acid Base Balance

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

Bone Metabolism

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

Other Abnormalities

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

Complications

Due to reduced erythropoietin production by kidney

Occurs when creatinine rises to >2.5-3mg/dL

Anemia management with Procrit and Arensp

Anemia

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

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

Treatment