DEFINITIONAcute renal failure (ARF) is the rapid impairment of renal func-tion, resulting in retention of products in the blood that are normally excreted by the kidneys.PHYSICAL FINDINGS AND CLINICAL PRESENTATIONThe physical examination should focus on volume status. The physical fi ndings noted here vary with the duration and rapidity of onset of renal failure.● Peripheral edema (Fig. 202–1)● Skin pallor, ecchymoses● Oliguria (however, patients can have nonoliguric renal fail-

ure), anuria● Delirium, lethargy, myoclonus, seizures● Back pain, fasciculations, muscle cramps● Tachypnea, tachycardia● Weakness, anorexia, generalized malaise, nauseaCAUSE● Prerenal: inadequate perfusion caused by hypovolemia, con-

gestive heart failure (CHF), cirrhosis, sepsis. Of community-acquired cases of ARF, 60% are caused by prerenal condi-tions.

● Postrenal: outlet obstruction from prostatic enlargement, ureteral obstruction (stones), bilateral renal vein occlusion. Postrenal causes account for 5% to 15% of community-acquired ARF.

● Intrinsic renal: glomerulonephritis, acute tubular necrosis, drug toxicity (Fig. 202–2), contrast nephropathy

● Causes of acute renal failure and evaluation are described in Table 202–1.

LABORATORY TESTS● Elevated serum creatinine: the rate of rise of creatinine is

approximately 1 mg/dL/day in complete renal failure.● Elevated blood urea nitrogen (BUN): BUN/creatinine ratio

is �20:1 in prerenal azotemia, postrenal azotemia, and

acute glomerulonephritis; it is �20:1 in acute interstitial nephritis and acute tubular necrosis

● Electrolytes (potassium, phosphate) are elevated; bicarbon-ate level and calcium are decreased.

● Complete blood count (CBC) may reveal anemia because of decreased erythropoietin production, hemoconcentration, or hemolysis.

● Urinalysis may reveal the presence of hematuria (GN), pro-teinuria (nephrotic syndrome), casts (see Fig. 201–1) (e.g., granular casts in acute tubular necrosis (ATN), red blood cell (RBC) casts in acute GN, white blood cell (WBC) casts in acute interstitial nephritis), eosinophiluria (acute intersti-tial nephritis). Urine chemistry in the differential diagnosis of ARF is described in Table 202–2.

● Urinary sodium and urinary creatinine should also be ob-tained to calculate the fractional excretion of sodium (FENa):

urine sodium/plasma sodium

urine creatinine/plasma creatinine � 100

The fractional excretion of sodium is �1 in prerenal failure and �1 in intrinsic renal failure in patients with a urine output of less than 400 mL/day.● Urinary osmolarity is 250 to 300 mOsm/kg in ATN, �400

mOsm/kg in postrenal azotemia, and �500 mOsm/kg in prerenal azotemia and acute glomerulonephritis.

● Additional useful studies are blood cultures for patients suspected of sepsis, liver function tests (LFTs), immuno-globulins, and protein immunoelectrophoresis in patients suspected of myeloma, and creatinine kinase in patients with suspected rhabdomyolysis.

691

Chapter 202: Acute renal failure 202

Chapter 202 Acute renal failure

Fig 202–1Fluid overload in acute renal failure (ARF). Gross pitting fl ank edema in a patient with ARF in whom femoral venous access has just been es-tablished to initiate hemodialysis.(From Johnson RJ, Feehally J: Comprehensive Clinical Nephrology, 3rd ed. St. Louis, Mosby, 2007.)

Fig 202–2Papillary necrosis—autopsy macroscopic appearance of papillary necrosis in a patient with long-standing analgesic nephropathy.(From Johnson RJ, Feehally J: Comprehensive Clinical Nephrology, 3rd ed. St. Louis, Mosby, 2007.)

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202 Section 8: Kidneys

Clinical features, typical urinalysis and confi rmatory tests for diagnosis of common causes of ARF. ACE, angiotensin-converting enzyme; ATN, acute tubular necrosis; FENa, fractional excretion of sodium; HUS, hemolytic-uremic syndrome; LVH, left ven-tricular hypertrophy; NSAIDs, nonsteroidal anti-infl ammatory drugs; TTP, thrombotic thrombocytopenic purpura; UNA, urine Na� concentration; SG, spe-cifi c gravity.

TABLE 202–1 Evaluation for the cause of acute renal failure (ARF)

Cause of acute renal failure Suggestive clinical features Typical urinalysis* Confi rmatory tests

Prerenal ARF Evidence of true volume depletion (thirst, postural or absolute hypo-tension and tachycardia, low jugu-lar vein pressure, dry mucous membranes and axillae, weight loss, fl uid output � input) or de-creased effective circulatory vol-ume (e.g., heart failure, liver failure), treatment with NSAIDs or ACE inhibitor

Hyaline casts; FENa � 10 mmol/L; SG � 1.018

Occasionally requires invasive hemodynamic monitoring; rapid resolution of ARF on restoration of renal perfusion

Intrinsic renal ARF

Diseases involving large renal vessels

Renal arterythrombosis

History of atrial fi brillation or re-cent myocardial infarct, nausea, vomiting, fl ank or abdominal pain

Mild proteinuria; occa-sionally, red blood cells

Elevated lactate dehydroge-nase with normal transami-nases, renal arteriogram

Atheroembolism Age usually �50 yr, recent manip-ulation of aorta, retinal plaques, subcutaneous nodules, palpable purpura, livedo reticularis, vascu-lopathy, hypertension

Often normal; eosinophi-luria; rarely, casts

Eosinophilia, hypocomple-mentemia, skin biopsy, renal biopsy

Renal vein thrombosis Evidence of nephrotic syndrome or pulmonary embolism, fl ank pain

Proteinuria, hematuria Inferior venacavogram and selective renal venogram; Doppler fl ow studies; MRI

Diseases of small vessels and glomeruli

Glomerulonephritis or vasculitis

Compatible clinical history (e.g., recent infection) sinusitis, lung hemorrhage, rash or skin ulcers, arthralgias, hypertension, edema

Red blood cell or granu-lar casts, red blood cells, white blood cells, mild proteinuria

Low C3, antineutrophil cyto-plasmic antibodies, antiglo-merular basement membrane antibodies, antinuclear anti-bodies, antistreptolysin 0, anti-DNase, cryoglobulins, renal biopsy

HUS or TTP Compatible clinical history (e.g., recent gastrointestinal infection, cyclosporine, fever, pallor, ecchy-moses, neurologic abnormalities

May be normal, red blood cells, mild proteinuria; rarely, red blood cell or granular casts

Anemia, thrombocytopenia, schistocytes on blood smear, increased lactate dehydrogenase, renal biopsy

Malignant hypertension Severe hypertension with head-aches, cardiac failure, retinopathy, neurologic dysfunction, papilledema

Red blood cells, red blood cell casts, proteinuria

LVH by echocardiography or electrocardiography, resolu-tion of ARF with control of blood pressure

ARF mediated by ischemia or toxin (ATN)

Ischemia Recent hemorrhage, hypotension (e.g., cardiac arrest), surgery

Muddy brown granular or tubule epithelial cell casts, FENa � 1%, U Na � 20 mmol/L, SG � 1.010

Clinical assessment and uri-nalysis usually suffi cient for diagnosis

Exogenous toxins Recent radiocontrast study, neph-rotoxic antibiotics or anticancer agents often coexistent with vol-ume depletion, sepsis, or chronic renal insuffi ciency

Muddy brown granular or tubular epithelial cell casts, FENa � 1%, UNa � 20 mmol/L, SG � 1.010

Clinical assessment and uri-nalysis usually suffi cient for diagnosis

Endogenous toxins History suggestive of rhabdomy-olysis (seizures, coma, ethanol abuse, trauma)

Urine supernatant tests positive for heme

Hyperkalemia, hyperphospha-temia, hypocalcemia, in-creased circulating myoglo-bin, creatine kinase MM, uric acid

History suggestive of hemolysis (blood transfusion)

Urine supernatant pink and positive for heme

Hyperkalemia, hyperphospha-temia, hypocalcemia, hyperuricemia, pink plasma positive for hemoglobin

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Chapter 202: Acute renal failure 202

TABLE 202–2 Urine chemistry in the differential diagnosis of acute renal failure

Prerenal acute Ischemic intrinsic Urine chemistry renal failure* acute renal failure†

Urine osmolality, Uosm (mOsm/kg H2O) �500 �250

Urine to plasma osmolality �1.5 �1.1

Urine specifi c gravity �1.018 �1.012

Plasma blood urea nitrogen-to-creatinine ratio �20 �10-15

Urinary urea nitrogen-to-plasma urea nitrogen ratio �8 �3

Urinary creatinine-to-plasma creatinine ratio �40 �20

Urinary Na+ concentration (mmol/L) �10 �20

Fractional excretion of Na+ (%)‡ �1 �2

Renal failure index§ UNa/Ucr/Pcr �1 �1

Urine sediment Hyaline casts Muddy brown granular casts

*Parameters suggesting prerenal failure are sometimes seen with nonoliguric acute tubular necrosis (ATN), acute glomerulonephritis, and early obstruction.†Parameters suggesting ATN may be misleading in prerenal failure in older patients, in those with preexisting renal impairment, and following diuretic administration.‡(Urine Na+/plasma Na� )/(urine creatinine/plasma creatinine) � 100.§Urine Na+/(urine creatinine/plasma creatinine) � 100.From Johnson RJ, Feehally J: Comprehensive Clinical Nephrology, 3rd ed. St. Louis, Mosby, 2007.

Cause of acute renal failure Suggestive clinical features Typical urinalysis* Confi rmatory tests

Endogenous toxins (cont’d)

History suggestive of tumor lysis (recent chemotherapy), myeloma (bone pain), or ethylene glycol ingestion

Uric acid crystals, dip-stick-negative proteinuria, oxalate crystals, respectively

Hyperuricemia, hyperkalemia, hyperphosphatemia (for tumor lysis); circulating or urinary monoclonal band (for my-eloma); toxicology screen, acidosis. osmolal gap (for eth-ylene glycol)

Acute diseases of the tubulointerstitium

Allergic interstitial nephritis

Recent ingestion of drug and fever, rash, or arthralgias

White blood cell casts, white blood cells (fre-quently eosinophiluria), red blood cells, rarely red blood cell casts, protein-uria (occasionally nephrotic)

Systemic eosinophilia, skin bi-opsy of rash area (leukocyto-clastic vasculitis), renal biopsy

Acute bilateral pyelonephritis

Flank pain and tenderness, toxic state, febrile

Leukocytes, proteinuria, red blood cells, bacteria

Urine and blood cultures

Postrenal ARF Abdominal or fl ank pain, palpable bladder

Frequently normal; he-maturia if stones, hemor-rhage, malignancy, or prostatic hypertrophy

Plain fi lm, renal ultrasonogra-phy, retrograde or antero-grade pyelography, CT

TABLE 202–1 Evaluation for the cause of acute renal failure (ARF) —cont’d

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202 Section 8: Kidneys

● Renal biopsy may be indicated in patients with intrinsic re-nal failure when considering specifi c therapy; major uses of renal biopsy are differential diagnosis of nephrotic syn-drome, differentiation of lupus vasculitis from other vascu-litides and of lupus membranous glomerulopathy, from id-iopathic membranous glomerulopathy, confi rmation of hereditary nephropathies on the basis of the ultrastructure, diagnosis of rapidly progressing glomerulonephritis, differ-entiation of allergic interstitial nephritis from ATN, and differentiation of primary glomerulonephritis syndromes. The biopsy may be performed percutaneously or by an open method. The percutaneous approach is favored and gener-

ally yields adequate tissue in more than 90% of cases. Open biopsy is generally reserved for uncooperative patients, those with a solitary kidney, and patients at risk for uncon-trolled bleeding.

IMAGING STUDIES● Chest x-ray is useful to evaluate for fl uid overload (Fig.

202–3) and for pulmonary renal syndromes (Goodpasture’s syndrome, Wegener’s granulomatosis).

● Ultrasound of kidneys (see Fig. 201–8) is used to evaluate for kidney size (useful to distinguish ARF from chronic renal failure [CRF]), presence of obstruction, and renal vascular status (with Doppler evaluation).

● Anterograde and/or retrograde pyelography (see Fig. 201–7) can be used for ruling out obstruction; useful in patients at high risk of obstruction

● ECG : hypocalcemia (Fig. 202–4), hyperkalemia (Fig. 202–5)TREATMENT● Stop all nephrotoxic medications.● Modify diet to supply adequate calories while minimizing ac-

cumulation of toxins; control fl uid balance appropriately.● Daily weight● Monitoring of renal function and electrolytes.● Modifi cation of dosages of renally excreted drugs● Treatment is variable with cause of ARF:

Fig 202–3Fluid overload in acute renal failure—severe pulmonary edema.(From Johnson RJ, Feehally J: Comprehensive Clinical Nephrology, 3rd ed. St. Louis, Mosby, 2007.)

PROLONGED QT INTERVAL DUE TO HYPOCALCEMIA

II

aVF

V5

V6

Fig 202–4Four ECG leads showing a prolonged QT interval caused by hypocal-cemia.(From Crawford MH, DiMarco JP, Paulus WJ [eds]: Cardiology, 2nd ed. St. Louis, 2004, Mosby.)

Mild to moderate Very severe

Lead I

Lead II

1 mV

1 sec

Moderate to severe

V1

V2

V1

V2

P

P

T

T

Fig 202–5The earliest change with hyperkalemia is peaking (“tenting”) of the T waves. With progressive increases in serum potassium, the QRS complexes widen, the P waves decrease in amplitude and may disappear, and fi nally, a sine wave pattern leads to asystole.(From Goldberger AL [ed]: Clinical Electrocardiography, 6th ed. St. Louis, Mosby, 1999.)

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695

Chapter 202: Acute renal failure 202Components of the hemodialysis system

Extracorporealcircuit

Dialyzer

WasteConcentrate

Water purification

Treated water

Sourcewater

Dialysis fluid

Dialysismachine

Fig 202–6Components of the hemodialysis system.(From Johnson RJ, Feehally J: Comprehensive Clinical Nephrology, 3rd ed. St. Louis, Mosby, 2007.)

A B

C D

Fig 202–7Implantation of the LifeSite hemodialysis access system (Vasca, Tewksbury, Mass). Cannulae are inserted over guidewires advanced into the infe-rior vena cava under fl uoroscopic control. A, After cutting cannula to appropriate length, the cannula is connected to the LifeSite valve. B, Valve is placed in tissue pocket; the fl at base is secured to the underlying fascia to reduce risk of valve rotation or migration. C, Fluoroscopy of LifeSite valves confi rms proper placement. D, Subcutaneous tissue and skin are closed. The LifeSite system is immediately ready for access by simple cannulation with a 14-gauge needle.(From Johnson RJ, Feehally J: Comprehensive Clinical Nephrology, 3rd ed. St. Louis, Mosby, 2007.)

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202 Section 8: Kidneys

1. Prerenal: IV volume expansion in hypovolemic patients2. Intrinsic renal: discontinuation of any potential toxins and treatment of condition causing the renal failure. Low-dose dopamine is often used to infl uence renal dysfunction and may offer transient improvement in renal physiology; however, there is lack of evidence that it offers signifi cant clinical benefi ts to patients with or at risk for acute renal failure.3. Postrenal: removal of obstruction

● General indications for initiation of dialysis:1. Florid symptoms of uremia (encephalopathy, pericarditis)2. Severe volume overload3. Severe acid-base imbalance4. Signifi cant derangement in electrolyte concentrations (e.g., hyperkalemia, hyponatremia)

● The components of the hemodialysis system are illustrated in Figure 202–6. The patient’s blood is circulated in a simple extracorporeal circuit and passed along one side of a semi-permeable membrane. Dialysis fl uid passes along the other side of the membrane in the opposite direction (countercur-rent) to optimize diffusion gradients. The main role of the dialysis machine is to supply dialysis fl uid with the intended fl ow rate, temperature, and chemical content safely. The machine mixes a preprepared concentrate of electrolytes with treated water to produce dialysis fl uid. It also removes a prescribed volume of ultrafi ltrate during the dialysis ses-sion. The development of fully implantable, subcutaneous, vascular access devices is a relatively recent innovation in

vascular access. The LifeSite hemodialysis access system (Vasca, Tewksbury, Mass) consists of two titanium alloy subcutaneous valves with connecting silicone cannulae, one for blood draw and one for blood return, that are placed in a central vein, preferably the right internal jugular vein. Fig-ure 202–7 illustrates the implantation of the LifeSite hemo-dialysis access system.

● Peritoneal dialysis (PD) should not be thought of as a tech-nique in competition with hemodialysis (HD) but rather as a complementary modality that can be offered to the patient with end-stage renal disease (ESRD) with some residual re-nal function. The basic principle of dialysis is the separation of substances in solution by their varying rates of diffusion down a concentration gradient through a semipermeable membrane. In PD, the peritoneum is used as the porous membrane. Fluid removal is along an osmotic gradient rather than as a result of a pressure gradient. Access to the peritoneal cavity (Fig. 202–8) is obtained by use of a cath-eter (Fig. 202–9).

● Renal function recovery (ability to discontinue dialysis) var-ies from 50% to 75% in survivors of ARF.

● Overall mortality rate in ARF is almost 50%, varying from 60% in patients with ATN to 35% in patients with prerenal or postrenal ARF.

● The combination of acute renal failure and sepsis is associ-ated with a 70% mortality rate.

Fig 202–8A recently implanted peritoneal dialysis catheter in situ.(From Johnson RJ, Feehally J: Comprehensive Clinical Nephrology, 3rd ed. St. Louis, Mosby, 2007.)

Common types of peritoneal dialysis catheter

2 cuff coil catheter

Straight 1 cuff catheter

Straight 2 cuff catheter

Swan neck catheter

Toronto Western catheter

Fig 202–9Common types of peritoneal catheters.(From Johnson RJ, Feehally J: Comprehensive Clinical Nephrology, 3rd ed. St. Louis, Mosby, 2007.)

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