Chapter 134: Renal Emergencies in Children

Acute kidney injury (AKI; previously called acute renal failure) is the sudden loss of renal function necessary to maintain normal fluid and electrolyte balance and clear metabolic waste.^1,2 AKI is typically manifested by an increase in serum creatinine, although the increase will not necessarily cause the creatinine to be outside the normal range. Use of serum creatinine alone to define AKI, however, is problematic because creatinine is an inaccurate estimate of glomerular filtration rate (GFR) and can be removed by dialysis, and variable cut-off values for creatinine have been used in AKI. Therefore, the international classification system, Kidney Disease: Improving Global Outcomes (KDIGO) (Table 134–1), is preferred. The system uses creatinine and urine output criteria and can be applied to both children and adults, minimizing practice variation.³

PATHOPHYSIOLOGY

AKI is the result of nephrotoxic and/or hypoxic injury to the glomeruli and renal tubules.¹ Reduced blood flow causes hypoxic injury and damages the proximal tubular cells. Common nephrotoxins include aminoglycosides, contrast agents, calcineurin inhibitors, amphotericin B, and nonsteroidal anti-inflammatory drugs.⁴ Inflammatory mediators intensify renal tubular damage.²

AKI is frequently classified based on three major anatomic locations of injury: prerenal, renal, and postrenal disease. Prerenal disease is typically caused by inadequate renal perfusion and is the most common class of AKI. Prerenal AKI is typically due to hypovolemia (e.g., bleeding or GI losses such as vomiting and diarrhea), decreased renal artery blood flow, or reduction in effective circulation (e.g., heart failure, cardiogenic shock, third spacing in septic shock). Renal disease or intrinsic renal disease occurs when there is structural damage to the renal parenchyma. Common causes of renal disease include glomerular diseases (e.g., pyelonephritis, nephrotic syndrome, glomerulonephritis, Henoch-Schönlein purpura), vascular diseases (e.g., hemolytic-uremic syndrome, thrombosis, vasculitides), interstitial diseases (e.g., interstitial nephritis, infections), and tubular injuries (e.g., ischemia, nephrotoxins, hypotension). Lastly, postrenal disease is typically due to an obstruction caused by congenital or acquired anomalies to the lower urinary tract. Examples include nephrolithiasis, renal vein thrombosis, pelvic masses (e.g., lymphoma, rhabdomyosarcoma), and urethral obstruction (posterior ureteral valves).

CLINICAL FEATURES

HISTORY

Direct the initial history to determine risk factors or causes for AKI. Many symptoms and signs relate to the underlying disorder, although patients can also be asymptomatic. Vomiting and diarrhea may suggest intravascular depletion and a prerenal cause of AKI. Other important historical features include history of streptococcal infection (suggests poststreptococcal glomerulonephritis), bloody diarrhea (hemolytic-uremic syndrome), and joint symptoms, rash, or purpura (Henoch-Schönlein purpura). Signs of obstruction include complete anuria or poor urinary stream. Symptoms of renal failure itself include nausea, anorexia (secondary to uremia), changes in urine output or color, edema (may be dependent, periorbital, scrotal/labial, or generalized), and headache from hypertension. Perform a full review of systems and obtain the medical history and pertinent family history.^1,2 Identify all medications used, including prescription and nonprescription drugs, herbals, and sport supplements.

PHYSICAL EXAMINATION

The physical examination should be thorough, with special emphasis on vital signs (especially blood pressure), weight, hydration status, and joint and skin findings.¹ Note the presence or absence of edema. Auscultate the lungs for rales, which suggest fluid overload, and the heart for uremic rubs. Palpate the abdomen for masses and organomegaly, which may indicate fluid overload in young children.

DIAGNOSIS

LABORATORY EVALUATION

Acute renal failure laboratory findings include alterations of renal function, such as elevated creatinine and BUN or an abnormal urinalysis.

Analysis of the urine can distinguish between prerenal, renal, and postrenal causes of acute renal failure. In children who are not toilet trained, it may be necessary to obtain a urine specimen by catheterization. In prerenal AKI, urinalysis may be normal. Hematuria, presence of casts, and proteinuria characterize the "active sediment" of glomerulonephritis. Proteinuria alone suggests nephrotic syndrome. WBCs and bacteria suggest infection. A urine dipstick test positive for blood in the absence of observed red blood cells (RBCs) suggests myoglobinuria or hemoglobinuria. Hyaline casts may be seen in acute tubular necrosis. Urine specific gravity is often high (>1.025) in prerenal acute renal failure and may be normal to low in acute tubular necrosis.

Obtain serum electrolyte levels when acute renal failure is suspected because hyperkalemia and other electrolyte abnormalities may require emergent treatment. Hyperkalemia may result from a combination of factors including reduced GFR, decreased tubular secretion of potassium, tissue breakdown with release of intracellular potassium, and metabolic acidosis resulting in transcellular movement of potassium. Other electrolyte abnormalities may include hyponatremia secondary to fluid retention or hypernatremia from dehydration in prerenal failure. Hyperphosphatemia from impaired renal excretion may lead to secondary hypocalcemia. A blood gas may show an anion gap metabolic acidosis secondary to impaired renal excretion of acid and reabsorption and regeneration of bicarbonate. A CBC is useful to identify anemia, hemolysis, and thrombocytopenia (characteristic of hemolytic-uremic syndrome), signs of systemic infection, or eosinophilia (interstitial nephritis). Additional studies are dictated by the clinical picture.

An ECG will identify cardiac arrhythmias and hyperkalemia. Renal biopsy is the definitive study for most cases of intrinsic renal disease and may be done on an outpatient or inpatient basis.^1,2

IMAGING

A chest radiograph can identify an increase in heart size or pulmonary edema. US identifies anatomic abnormalities, hydronephrosis, and/or hydroureter. Voiding cystourethrogram is obtained in boys with suspected posterior urethral valves. Additional imaging depends on the differential diagnosis.

TREATMENT

Treatment of acute renal failure is different for prerenal, renal, and postrenal failure. In all cases, careful monitoring of vital signs, including baseline weight and urine output, is necessary. In prerenal failure, treat dehydration and hypovolemia with a 10- to 20-mL/kg crystalloid bolus of normal saline. If hemorrhagic shock is the cause for hypovolemia, initiate a crystalloid bolus until blood products are available. Packed RBCs are transfused at a volume of 10 mL/kg. Fresh frozen plasma and platelets may be necessary in massive hemorrhage.

In renal failure from intrinsic renal disease, the specific cause must be identified and treated. Depending on the clinical state, manage oliguria with fluid restriction, limiting replacements to insensible losses only. Discontinue all nephrotoxic medications or adjust dose for GFR. Treat hypertension with antihypertensive agents (avoid angiotensin-converting enzyme [ACE] inhibitors and angiotensin receptor blockers) or diuretics (see "Hypertension" below).

Manage oliguria of postrenal failure with fluid restriction and treatment of hypertension. A Foley catheter may be necessary to relieve the obstruction. In all types of AKI, electrolyte management is important. The management of life-threatening hyperkalemia and hyponatremia is discussed in chapter 129, "Fluid and Electrolyte Therapy in Infants and Children."

When conservative management fails, consider acute renal replacement therapy (dialysis). Indications for acute renal replacement therapy are severe electrolyte abnormalities, fluid overload not relieved by administration of loop diuretics, and intractable metabolic acidosis not responding to bicarbonate therapy. Peritoneal dialysis is the preferred method of acute dialysis for children because it is inexpensive and requires less expertise to perform than hemodialysis.^1,2

DISPOSITION AND FOLLOW-UP

Although the primary care physician can manage mild renal insufficiency caused by dehydration, pyelonephritis, postinfectious glomerulonephritis, or Henoch-Schönlein purpura on an outpatient basis, consult a pediatric nephrologist for the management of more significant renal insufficiency, which often requires inpatient therapy. Children with hypertension with or without other findings require inpatient evaluation and management. Pediatric urology consultation is needed for postrenal failure.¹ Admit children with severe electrolyte abnormalities and fluid overload to a pediatric intensive care unit.

Nephrotic syndrome is a chronic disease in children that alters permeability at the glomerular capillary wall, which causes a urinary loss of protein. The disease is classically characterized by proteinuria (>40 milligrams/m² in 24 hours), hypoalbuminemia (serum albumin <30 grams/L), hyperlipidemia, and edema. However, hyperlipidemia and edema are not consistently present. Nephrotic syndrome can be primary (involving only the kidney) or secondary (multisystem). The cause is unknown.

PATHOPHYSIOLOGY

The glomerular membrane is damaged, resulting in increased permeability of the glomerulus to proteins normally not able to pass through the glomerular capillary wall. Increased permeability results in the two diagnostic hallmarks of nephrotic syndrome: proteinuria and hypoproteinemia. Nephrotic syndrome also leads to salt and water retention. The combination of low intravascular oncotic pressure from the loss of proteins, coupled with the retention of salt and water, gives rise to the clinical feature of edema. As fluids shift to the extracellular space, the kidney is stimulated through the renin-angiotensin-aldosterone system to increase distal sodium reabsorption, which exacerbates the cycle.⁵

Although viral upper respiratory tract infection often precedes symptomatic nephrotic syndrome, a causal link has not been established. The classification of primary nephrotic syndromes includes minimal change disease, focal segmental sclerosis, membranous nephropathy, membranoproliferative nephritis, and proliferative nephritis (diffuse, focal, or mesangial). Causes of secondary nephrotic syndrome include systemic diseases such as lupus, Henoch-Schönlein purpura, sickle cell anemia, and systemic infections, as well as potential drug or toxin exposure (e.g., heavy metals). TORCH (toxoplasmosis, syphilis, varicella, rubella, cytomegalovirus, and herpes simplex virus) infections may cause a congenital nephrotic syndrome in neonates.

CLINICAL FEATURES

HISTORY AND COMPLICATIONS

Edema is the most common complaint. Focus the history on the duration and location of edema. Anasarca consists of marked peripheral edema, ascites, scrotal or vulvar edema, and severe periorbital edema. Shortness of breath, cough, and orthopnea suggests a pleural effusion. Ask about urine output, because oliguria is often associated with more severe edema. Nausea, vomiting, and anorexia suggest ascites or edema of the bowel wall. Review of systems should note fever, fatigue, and headache as well as the character of the urine (foamy, bloody, and tea colored).² The presence of hematuria, hypertension, or reduced renal function, age at onset, medical and family history of disease, and biopsy findings are all important predictors of disease outcome.

The main life-threatening complications of nephrotic syndrome are severe infection and thromboembolic events (venous and arterial). Serum complements, antibodies, and coagulation factors are lost as protein in the urine, leading to relative immunocompromise. Steroid therapy for nephrotic syndrome increases the risk of infection. Hyperlipidemia may lead to hyperviscosity, and increased levels of fibrinolytic inhibitors increase thrombotic risks.

PHYSICAL EXAMINATION

Rebound abdominal tenderness, ascites, and scrotal or labial swelling are potential findings.⁵ Perform a full cardiopulmonary and abdominal exam. Auscultate for findings of pleural effusion and pulmonary edema. Be careful not to confuse facial swelling due to nephrotic syndrome with swelling secondary to allergic reaction.

DIAGNOSIS

The four diagnostic criteria of nephrotic syndrome are as follows:

1. Hypoproteinemia with disproportionately low albumin level (<3 grams/dL)

2. Urine protein (milligrams/deciliter) to urine creatinine (milligrams/deciliter) ratio >2 in a first morning void or a 24-hour urine protein loss that exceeds 50 milligrams/kg or 40 milligrams/m²

3. Hypercholesterolemia (>200 milligrams/dL)²

4. Generalized edema

Renal biopsy is not indicated during the initial episode of acute nephrotic syndrome. Renal biopsy may be done when there is a definitive need to make a specific diagnosis for therapeutic reasons or to provide a diagnosis.^2,5

LABORATORY EVALUATION

In general, blood and urine samples are sent for study to confirm the diagnosis of nephrotic syndrome (tests for proteinuria, hypoproteinemia, and hyperlipidemia), distinguish primary from secondary causes (tests for hematuria, serum immunoglobulin and complement levels, and antinuclear antibody level; hepatitis serologic testing), and aid in management (CBC, serum electrolyte levels, and renal function test). Serum creatinine may be normal for age and height. Total serum calcium is often low, although ionized calcium is usually normal. Serum sodium level is low secondary to increased triglycerides. Imaging studies are rarely indicated unless there is clinical concern for pulmonary edema or effusions. Symptoms or signs suggestive of potential thrombotic complications of nephrotic syndrome should prompt the appropriate evaluation (e.g., duplex US of renal vessels, CT angiography).

TREATMENT

ED MANAGEMENT

The goal is to treat acute symptoms, make the diagnosis of nephrotic syndrome, and arrange for appropriate follow-up. Treat hypovolemic shock with isotonic fluid, even if edema is severe. For the mildly to moderately dehydrated patient, provide oral rehydration with small, frequent aliquots of sodium-deficient solutions. Treat volume overload with furosemide, 1 to 2 milligrams/kg. Diuretics may not be effective when there is profound hypoalbuminemia, and in that situation, infusion of albumin (0.5 to 1.0 gram/kg) followed by furosemide may be effective, but intensive care monitoring is required. Treat infection or thrombotic complications as clinically indicated.

SPECIFIC TREATMENT OF NEPHROTIC SYNDROME

The mainstay of the treatment of nephrotic syndrome is oral corticosteroids, but the response to steroids varies with the cause. Minimal change disease and mesangial proliferative nephritis are often steroid responsive; membranous nephropathy may respond to steroids; focal segmental sclerosis and membranoproliferative nephritis are typically steroid resistant.^2,5 When indicated, prednisone is often started at 2 milligrams/kg/d in two or three divided doses, or 60 milligrams/m² for the initial dose and 40 to 60 milligrams/m² for the subsequent doses, given daily for 6 weeks with an additional 6 weeks of alternate-day administration. No steroid taper is required for this initial therapy.⁶ In patients with known steroid-responsive disease who experience relapse, the ED physician may restart steroids as above in consultation with a pediatric nephrologist. In steroid-resistant nephrotic syndrome, the nephrologist must be consulted for initiation of medications. There are three types of medications that can be used for steroid-resistant nephrotic syndrome (5% of cases): immunosuppressive, immunostimulatory, and nonimmunosuppressive medications. Examples include cyclosporine, cyclophosphamide, chlorambucil, and levamisole.⁶

DISPOSITION AND FOLLOW-UP

Admit patients with severe edema, pulmonary effusions or respiratory symptoms, or signs and symptoms suggestive of systemic infection or thrombotic complications to the hospital. Children with mild or moderate edema can often be treated as outpatients with a low-salt (<2 grams/d) diet and close follow-up with their primary care physician or pediatric nephrologist.²

Children with nephrotic syndrome are at high risk for bacterial peritonitis from Streptococcus pneumoniae and should receive the pneumococcal (23-valent) vaccine to avoid peritonitis. The varicella vaccine should also be administered to children with nephrotic syndrome once they are in remission and no longer receiving steroid therapy.⁵

Glomerulonephritis is a spectrum of inflammatory disorders characterized by hematuria and proteinuria. Signs of glomerulonephritis vary from asymptomatic proteinuria and microscopic hematuria to gross hematuria, nephrotic syndrome, hypertension, and impaired renal functioning requiring renal replacement therapy.² Glomerulonephritis is caused by several disorders, all of which cause inflammation leading to glomerular injury. Examples of hereditary glomerular diseases include systemic lupus erythematosus nephritis, thin glomerular basement membrane disease, and Alport's syndrome.^2,7 Poststreptococcal glomerulonephritis, immunoglobulin A (IgA) nephropathy, and Henoch-Schönlein purpura will be discussed in this section.

PATHOPHYSIOLOGY

Glomerulonephritis is an inflammatory process affecting the glomerulus. It can be caused by immune-mediated disorders, inherited disorders, or postinfection sequelae. Glomerulonephritis usually results from deposition of immune complexes within the glomeruli. These immune complexes activate a number of processes including complement activation, leukocyte recruitment, and release of growth factors and cytokines. This leads to inflammation and injury. Sclerosis occurs within the glomeruli, and fibrosis occurs in the tubulointerstitial cells.^2,7

Glomerulonephritis may be classified as primary (isolated to the kidney) or secondary (a result of a systemic disorder). There are four main presentations: acute glomerulonephritis, rapidly progressive glomerulonephritis, recurrent macroscopic hematuria, and chronic glomerulonephritis. Although glomerulonephritis caused by streptococcal disease or Henoch-Schönlein purpura usually resolves completely and without sequelae, glomerulonephritis from other causes can progress to renal damage and ultimately end-stage renal failure.²

CLINICAL FEATURES

Glomerulonephritis is often associated with hypertension, which may cause headaches when severe. Symptoms related to hypertension may be the chief complaint of a child with undiagnosed glomerulonephritis.^2,7 Patients may complain of bloody or foamy urine (a result of proteinuria), oliguria, fatigue, and lethargy.^2,7 In glomerulonephritis, the urinalysis demonstrates macroscopic or microscopic hematuria, RBC casts, and proteinuria. Microscopic examination of urinary sediment shows dysmorphic RBCs and RBC casts. The physical examination is often normal. The blood pressure may be elevated. Other examination findings depend on the underlying disorder.

LABORATORY EVALUATION

The microscopic urinalysis demonstrates dysmorphic RBCs and RBC casts. Send urine for culture, because proteinuria and hematuria may represent urinary tract infection, although RBC casts are not typical of infection.⁷ Other useful studies include a CBC, creatinine level, and electrolytes. Serum albumin level is often reduced. Send serum complement levels (C3 and C4), because complement proteins (C3) are decreased in >90% of patients with poststreptococcal glomerulonephritis, whereas levels are usually normal in patients with IgA nephropathy. Consider streptococcal serologic tests (antistreptolysin-I and streptozyme).⁷ More specific tests may be needed to make a clear diagnosis in illnesses with systemic manifestations such as Henoch-Schönlein purpura and systemic lupus erythematosus. A renal biopsy is often required for definitive diagnosis in glomerulonephritic disorders.⁷

POSTSTREPTOCOCCAL GLOMERULONEPHRITIS

Poststreptococcal glomerulonephritis is caused by prior infection with group A β-hemolytic streptococci. Only certain strains of this group are "nephritogenic," and infection of the pharynx is the most common type of infection leading to acute glomerulonephritis, which occurs on average 7 to 14 days after infection. Group A β-hemolytic streptococci stimulate immune complex formation secondary to deposition of streptococcal nephritogenic antigens within the glomerulus. Other infections such as Staphylococcus aureus and S. epidermidis may also lead to renal disease, usually with a longer latency period.

Clinically, poststreptococcal glomerulonephritis consists of microscopic or gross hematuria, proteinuria, hypertension, and edema. Children may give a history of a recent upper respiratory tract or skin infection or have tea-colored urine. The most common serologic markers include an anti-streptolysin O titer, which is typically elevated, and a serum C3 level, which is typically decreased.⁸ The recovery phase, where proteinuria and gross hematuria begin to resolve, starts after resolution of the patient's fluid overload.⁸

Treatment is largely supportive. Symptoms of poststreptococcal glomerulonephritis usually resolve in a few weeks. Hypertension rarely requires long-term treatment and tends to resolve within 1 to 2 weeks.⁸ Renal biopsy is not indicated for diagnosis, unless atypical clinical features are present.⁸ Asymptomatic patients with probable poststreptococcal disease and normal vital signs are eligible for discharge after consultation, and arrangement for follow-up, with a nephrologist.

IGA NEPHROPATHY

IgA nephropathy, also known as Berger's disease, is an autoimmune disease that is responsible for up to 10% of acute glomerulonephritis in the United States. Initially, IgA is deposited on the mesangial cells of the kidney. This alone is not enough to cause IgA nephropathy. In addition, there needs to be reduced IgA clearance, development of glomerular injury, and complement activation, all resulting from dysregulation of mucosal-type IgA immune responses. The cause is unknown.

Clinically, IgA nephropathy may present one of three ways: macroscopic hematuria, microscopic hematuria with mild proteinuria, or acute rapidly progressive glomerulonephritis with edema, hypertension, and renal insufficiency. Macroscopic hematuria is often concurrent with an upper respiratory tract infection and is called synpharyngitic hematuria. The diagnosis is typically based on the clinical history and laboratory data (including urinalysis). Renal biopsy is confirmatory.

Treatment is symptomatic. Immunosuppressant therapy may be initiated to treat underlying inflammation, depending on disease severity. ACE inhibitors or angiotensin receptor blockers may be used to control blood pressure, particularly in patients with proteinuria.⁹ IgA nephropathy can either completely resolve or progress to end-stage renal disease.⁹ Concern for a IgA nephropathy in the ED warrants an outpatient referral to nephrology. Rapidly progressive glomerulonephritis requires admission.

HENOCH-SCHÖNLEIN PURPURA

Henoch-Schönlein purpura, also known as IgA vasculitis, is a form of systemic vasculitis associated with IgA deposition in the small vessels of the body. Palpable purpura, arthritis/arthralgias, abdominal pain, and renal disease make up the classic presentation tetrad. Henoch-Schönlein purpura nephritis is often asymptomatic, and it is extremely important to follow up to detect persistent renal inflammation.¹⁰ Full discussion of Henoch-Schönlein purpura is in chapter 130, "Acute Abdominal Pain in Infants and Children," and we focus on the renal manifestations here.

Renal complications occur in 20% to 54% of patients with Henoch-Schönlein purpura and include gross or microscopic hematuria, proteinuria, or nephritic syndrome.¹¹ Of the children diagnosed with Henoch-Schönlein purpura, 40% have mild nephritis, manifested only by microscopic hematuria or low-grade proteinuria.¹² Renal complications may develop any time over a period of 28 days, and 2% of children may develop long-term renal impairment.¹³ Obtain a urinalysis to identify RBCs, casts, and protein. Treatment focuses on hydration, rest, and analgesics. Treatment with corticosteroids in Henoch-Schönlein purpura with renal involvement is controversial and may lead to increased recurrence of disease. Nephrology consultation is recommended.

HEMOLYTIC-UREMIC SYNDROME

Hemolytic-uremic syndrome is a multisystem disorder resulting in acute renal failure, thrombocytopenia, and microangiopathic hemolytic anemia. Hemolytic-uremic syndrome is one of the most common causes of AKI in children and typically occurs in those <10 years old. It is classified as typical (diarrhea associated) or atypical. In children, Shiga toxin–producing Escherichia coli causes 90% of hemolytic-uremic syndrome cases, presenting with a prodrome of diarrhea.¹⁴ Other causes of hemolytic-uremic syndrome are S. pneumoniae infection, genetic disorders, oral contraceptive use, pregnancy, and malignancy.

PATHOPHYSIOLOGY

Epidemic hemolytic-uremic syndrome is usually caused by infection with E. coli O157:H7, an organism associated with ingestion of undercooked meat, unpasteurized milk, and contaminated fruits and vegetables. E. coli O157:H7 produces a Shiga toxin, which is absorbed from the intestines into the circulation, causing microangiopathic intravascular thrombosis, RBC hemolysis, thrombocytopenia (due to platelet consumption), and decreased glomerular perfusion.¹⁴ Microthrombi are deposited in kidney parenchyma, causing hypertension, oliguria, and anuria.¹⁵ Renal involvement ranges from mild renal insufficiency to acute renal failure requiring dialysis.

In atypical hemolytic-uremic syndrome associated with S. pneumoniae, pathogenesis is initiated by the pneumococcal enzyme neuraminidase. This enzyme cleaves N-acetylneuraminic acid from the surface of RBCs and endothelial cells, uncovering the T antigen on the surface of endothelial cells. This in turn leads to an immune response, initiating the cascade leading to hemolytic-uremic syndrome.¹⁶

CLINICAL FEATURES

The majority of hemolytic-uremic syndrome is associated with E. coli enteritis, and the disease starts with nausea, vomiting, and bloody diarrhea with or without fever. Within a week, anemia, oliguria, and seizures or encephalopathy develop. Other complications include hypertension, heart failure, intussusception, diabetes mellitus, acidosis, and colitis.¹⁵ A careful dietary and travel history may identify a potential source of infection to aid public health officials assess epidemic outbreaks.

The differential diagnosis of diarrhea-associated hemolytic-uremic syndrome includes acute gastroenteritis, appendicitis, colitis, intussusception, inflammatory bowel disease, and perforation. Petechiae, hemolysis, and thrombocytopenia are seen in disseminated intravascular coagulation, thrombotic thrombocytopenia purpura, and systemic lupus erythematosus. Some of the symptoms of hemolytic-uremic syndrome may also be seen in malignant hypertension and renal vein thrombosis.

LABORATORY EVALUATION

Microangiopathic hemolytic anemia, one of the cardinal features of hemolytic-uremic syndrome, may be profound with a hemoglobin level between 5 and 9 grams/dL. A peripheral smear demonstrates schistocytes, helmet cells, and burr cells. The Coombs test is negative. The platelet count is <150 000/mm³. The WBC count may be elevated.

Hyponatremia and hyperkalemia develop as a result of metabolic acidosis from renal failure, and hyperbilirubinemia results from acute hemolysis.

Obtain a stool specimen to test for Shiga toxin, and specifically test for E. coli O157:H7. Urinalysis demonstrates gross or microscopic hematuria with granular and hyaline casts and variable proteinuria and leukocyturia.

TREATMENT

ED management is supportive. Correct life-threatening electrolyte disturbances, and treat hypovolemia with IV fluid boluses (10 to 20 mL/kg normal saline). Exercise cautious use of fluids to prevent fluid overload, particularly in patients with oliguria/anuria.¹⁴ Antibiotics are contraindicated in pediatric diarrheal illness and may increase the risk hemolytic-uremic syndrome.¹⁵ Antiperistaltic agents increase the risk for systemic complications associated with E. coli infection and are also contraindicated.¹⁴ Blood transfusions may be needed for severe anemia. Platelet transfusion is not recommended because it could worsen the thrombotic process. For atypical hemolytic-uremic syndrome, consult with hematology for possible plasma exchange therapy.

All patients with hemolytic-uremic syndrome require hospitalization. Patients with neurologic symptoms and oliguric renal failure should be admitted to the intensive care unit.¹⁵ Renal replacement therapy is required in 15% to 70% of cases of acute hemolytic-uremic syndrome.¹⁴ Most children (90%) survive the acute phase of the illness, and most regain normal renal function.

Renal tubular acidosis is rare. In the absence of diarrhea, it is defined as hyperchloremic metabolic acidosis with a normal anion gap and a normal to near-normal GFR.^12,17

In children, renal tubular acidosis is typically secondary to an inherited or acquired defect that affects the kidney's ability to manage bicarbonate, acid, and ammonia. Renal tubular acidosis develops because of failure of reabsorption of bicarbonate in the distal tubule (type I), failure of excretion of hydrogen ions in the proximal nephron (type II), or inability to acidify the urine in the setting of low serum aldosterone level or aldosterone resistance (type IV). For example, Fanconi's syndrome causes a type II renal tubular acidosis and may be associated with hypophosphatemia and rickets. Types I and II renal tubular acidosis result in hyperchloremic metabolic acidosis. Type IV renal tubular acidosis results in hyperkalemia, acidemia, and a low urinary pH.^12,17

There is no single symptom complex that brings children with renal tubular acidosis to medical attention. Chronic acidosis is associated with failure to thrive, and this may result in an ED visit. Depending on the type of renal tubular acidosis, symptomatic hypokalemia or hyperkalemia (weakness, nausea, constipation), rickets, or nephrolithiasis may prompt an ED visit. Often the diagnosis of renal tubular acidosis is suggested by abnormal results on serum chemistry and urine studies that are incidentally discovered in the process of evaluation for unrelated complaints. Table 134–2 describes the typical laboratory findings in each type of renal tubular acidosis.

Acute treatment consists of correcting the underlying electrolyte and acid-base abnormalities (see chapter 129). Maintenance treatment includes oral bicarbonate therapy and monitoring of serum potassium for all types of renal tubular acidosis, vitamin D and sodium phosphate for type II renal tubular acidosis, and loop diuretics and fludrocortisone for mineralocorticoid deficiency in type IV renal tubular acidosis.

Pediatric hypertension is increasing in incidence, with a prevalence of 2.5% to 5%.¹⁸ This increase is related to higher rates of childhood obesity, greater salt intake, hyperlipidemia, and decreased physical activity.¹⁸ Hypertension is defined as average systolic blood pressure and/or diastolic blood pressure greater than the 95th percentile or higher for sex, age, and height on three or more occasions.¹⁹

Hypertensive urgency is a severely elevated blood pressure without evidence of target organ damage that, left untreated, may cause end-organ damage.

Hypertensive crisis is defined as blood pressures exceeding the 99th percentile for age and sex with acute end-organ damage and requires immediate treatment.²⁰ Generally, the CNS, kidneys, and cardiovascular system are the organs most likely to be damaged secondary to hypertension. Hypertensive crises in younger children are usually secondary to an underlying disease.

Essential hypertension is uncommon in younger children and is more prevalent in adolescents.²¹ Renal disease (glomerulonephritis, hemolytic-uremic syndrome, chronic infections, obstructive lesions, and renal vascular disease) is the most common cause of secondary hypertension in children. Endocrine causes of hypertension include tumors that secrete vasoactive peptides (pheochromocytoma), abnormal levels of endogenous steroid hormones (Cushing's syndrome), adrenocortical steroid therapy, and hyperthyroidism. Hypertension may also result from congenital heart disease such as coarctation of the aorta. Elevated intracranial pressure may also lead to hypertension in an attempt by the body to maintain cerebral perfusion pressure and can be caused by space-occupying lesions, acute hemorrhage, infection, or obstruction to cerebrospinal fluid flow. Exogenous medications or toxins may also cause hypertension. Table 134–3 outlines the common causes of hypertension by age group.

CLINICAL FEATURES

HISTORY AND COMORBIDITIES

Focus on signs of hypertension and determine if end-organ damage is present.²⁰ The most common signs suggesting primary hypertension in children are headache, sleep disturbances (falling asleep, daytime tiredness), chest pain, and abdominal pain.¹⁸ Identify any medications or substances associated with blood pressure elevation, such as oral contraceptives, steroids, and illicit drugs (e.g., cocaine, amphetamines). Inquire about visual changes, headache, epistaxis, chest pain, urine output, hematuria, fever, and changes in mental status. Palpitations, weight loss, flushing, and diarrhea may suggest an endocrine cause. Ask about a family history of essential hypertension, diabetes, obesity, renal disease, hyperlipidemia, stroke, or endocrinopathy.^19,20 For those with an established diagnosis of hypertension, ask about medication adherence.

PHYSICAL EXAMINATION

Obtain an accurate height and weight, and determine percentiles for age.¹⁹ Obtain four-limb blood pressures (a lower blood pressure in the lower extremities compared to the upper extremities or left versus right arms may indicate aortic coarctation), respiratory rate, heart rate, and oxygen saturation. Perform a comprehensive physical examination, including a funduscopic examination (for retinal hemorrhages, papilledema, infarcts) and a neurologic examination.²⁰ Assess the heart and lungs for signs of congestive heart failure or structural disease (gallops, murmurs, rales). Palpate the abdomen to exclude masses or pregnancy. Auscultation of an abdominal bruit may suggest renovascular disease.

LABORATORY EVALUATION

Assess renal function with a serum BUN, creatinine, electrolytes, glucose, plasma rennin activity, aldosterone levels, and microscopic urinalysis.¹⁸ Obtain a CBC and reticulocyte count to look for rheumatic disorders, appropriate marrow response, and signs of anemia.¹⁸ Perform a urine pregnancy test in pubertal girls. Urine drug screening is indicated if intoxication is suspected. Ordering of more esoteric tests for endocrine abnormalities should be left to subspecialists.

IMAGING

Obtain a chest radiograph and ECG. Obtain a head CT if neurologic findings are present.²⁰ Renal US is indicated to rule out structural kidney abnormalities. If suspicion for renovascular disease is high, then obtain a CT or MRI. Obtain an echocardiogram to look for left ventricular hypertrophy and to rule out cardiac causes of hypertension.

TREATMENT

Most patients with mild to moderate elevation of blood pressure in the ED are discharged with instructions for follow-up for outpatient evaluation and treatment.

Hypertensive urgency may be treated with oral antihypertensives.¹⁸ Treatment of hypertensive emergency begins with evaluation and stabilization of the airway, breathing, and circulation. Obtain IV or IO access and start cardiac monitoring; consider placement of a Foley catheter and arterial line. The goal is to reduce the mean arterial pressure by ≤25% over the first 8 hours, followed by a gradual reduction to normal values over the next 26 to 48 hours.²² Reducing the blood pressure too aggressively can lead to ischemic complications such as acute neurologic issues, blindness, and renal failure.¹⁸

Recommendations regarding the most useful drugs for treating severe hypertensive emergency and urgency in children are listed in Table 134–4 and Table 134–5.^22,23 Medications should be chosen according to their side effect profile, availability, and physician familiarity.²⁰

Many nephrologists administer short-acting nifedipine to treat moderate to severe hypertension in the setting of primary renal disease. Although it is generally safe and effective,²⁴ there are reports of adverse neurologic events due to rebound hypertension.

DISPOSITION AND FOLLOW-UP

Mild hypertension should be managed on an outpatient basis by the primary care provider or subspecialist. Hypertensive urgencies and emergencies require ED stabilization and initial pharmacologic treatment in the ED with subsequent admission to the intensive care unit or medical ward depending on the degree of end-organ damage and the response to initial interventions.

Hematuria is the presence of an increased number of RBCs (≥5 RBCs/µL of urine). Hematuria may be macroscopic (apparent to the naked eye) or microscopic (apparent only on urinalysis). It is frequently asymptomatic.

Hematuria can be divided into three types: macrohematuria, transient hematuria, and persistent microhematuria. Macroscopic hematuria is most frequently caused by urinary tract infections or blunt abdominal trauma. Other causes include nephrolithiasis, poststreptococcal glomerulonephritis, IgA nephropathy, and malignancy. Transient hematuria may be caused by strenuous exercise, trauma, menstruation, bladder catheterization, and fever. Persistent microhematuria can be seen in benign familial hematuria, idiopathic hypercalciuria, IgA nephropathy, Alport's syndrome, and sickle cell trait or anemia or with drugs/toxins.

CLINICAL FEATURES

HISTORY AND COMORBIDITIES

Obtain a complete history, because the differential diagnosis is broad. Distinguish between transient, persistent, and recurrent hematuria.^2,25 Associated dysuria, urinary frequency and urgency, fever, and abdominal or flank pain suggest infection or urolithiasis (see chapter 94, "Urologic Stone Disease" in the adult section). A history of an upper respiratory tract infection, sore throat, or skin infection may suggest postinfectious glomerulonephritis. A current infectious process is suspicious for IgA nephropathy. For transient hematuria, ask about blunt abdominal trauma, recent catheterization, or menstruation.²⁵ The color of the urine (pink, red, or tea colored) and the timing during micturition—at the beginning (associated with pathology of the urethra), throughout micturition (associated with bleeding above the bladder neck), or at the end of micturition (associated with pathology of the bladder neck, posterior urethra, or prostate)—provides useful diagnostic information.^2,25 Ask about joint pain and rash (Henoch-Schönlein purpura^25,26 or lupus²). Some drugs associated with hematuria are nonsteroidal anti-inflammatory drugs, anticonvulsants, warfarin, diuretics, penicillin, and chlorpromazine.¹³ Recent vigorous exercise can cause hematuria, which resolves after a period of rest.² Obtain a family history carefully, because many causes of hematuria in children are inherited. Questions about family history should be directed to information regarding deafness, hematuria, hypertension, coagulopathy, hemoglobinopathy, calculi, renal failure, dialysis, and transplant.^2,13 Staining reported as "blood on the diaper" of an infant without other symptoms may represent benign urinary crystals, extra–urinary tract blood (e.g., vaginal bleeding in female neonates), or blood from the GI tract. The presence of amorphous crystals in the urine is a common and benign finding in neonates, and because these crystals are often pink or orange, they may be interpreted as blood by parents. Dipstick testing is negative for blood in this situation.

PHYSICAL EXAMINATION

The physical examination findings vary depending on the cause of hematuria suggested by historical information.^2,25 Obtain vital signs to identify hypertension or a fever. Assess for signs of respiratory infection, joint swelling, and skin rashes. Perform a careful GU examination to identify a source of external bleeding such as a periurethral tear.

DIAGNOSIS

LABORATORY EVALUATION

The laboratory evaluation begins with confirmation of hematuria. Medications such as chloroquine, isoniazid, malin, and nitrofurantoin may cause a red-brown discoloration of the urine.²⁷ Similarly, foods such as beets, rhubarb, or blackberries may also cause discoloration. Because such urinary discoloration may be misinterpreted by parents as blood, screen with a urine dipstick test, which can exclude hematuria. A positive dipstick test result, however, must be followed by microscopic evaluation. Microscopic examination of the urine helps narrow the differential diagnosis: dysmorphic RBCs and casts suggest glomerulonephritis; WBCs and bacteria suggest infection; eosinophils may be seen in interstitial nephritis; and intact RBCs suggest lower tract causes of hematuria. Urinary crystals or stones may be seen in urolithiasis. A dipstick test result positive for blood without evidence of RBCs on microscopy suggests hemoglobinuria or myoglobinuria. Further evaluation of the urine includes rapid or quantitative evaluation for proteinuria, which can be seen in nephritis, nephrotic syndrome, and orthostatic proteinuria.¹³ Obtain other laboratory studies to identify serious causes of hematuria, such as hemolytic-uremic syndrome, acute poststreptococcal glomerulonephritis, or renal insufficiency.

IMAGING

US is the imaging method of choice for macroscopic hematuria without proteinuria or RBC casts in the urine and is done to rule out malignancy or structural defects. For patients with trauma, macroscopic hematuria, or >20 RBCs/high-power field a more complete anatomic evaluation is needed, including CT, angiography, or retrograde urethrography depending on the history and clinical suspicion.

TREATMENT

The treatment of hematuria, like its evaluation, depends on the suspected cause. Most children without signs of major or life-threatening etiologies can be managed as outpatients. Children with isolated microscopic hematuria do not require an extensive evaluation if the blood pressure and urine output are normal. Hematuria requires a more rigorous evaluation when the blood pressure is elevated or there is significant proteinuria, so consult with a nephrologist. Refer to a urologist if there is suspicion of a urogenital tract anatomic abnormality, obstructing calculi, tumor, or recurrent nonglomerular macroscopic hematuria.¹³

Chronic kidney disease is defined as the presence of kidney damage as manifested by abnormalities in blood or urine tests, imaging tests, or kidney biopsy or a GFR >60 mL/min/1.73 m² for 3 months or more, regardless of the diagnosis.¹⁹ End-stage renal disease occurs when the GFR is <10% of normal for age.²⁸ Mortality in end-stage renal disease usually results from cardiovascular causes (40% to 50%) and infection (20%).²⁹ The only definitive treatment for end-stage renal disease is transplantation; however, the morbidity and mortality associated with chronic renal replacement therapy have decreased.

The National Kidney Foundation classifies chronic kidney disease into five separate stages.³⁰ The recommended method for determination of GFR is with spot urine and serum creatinine using either the Schwartz or Counahan calculation. Twenty-four–hour urine collections for creatinine are no longer recommended.

Stage 1: GFR ≥90 mL/min/1.73 m² (kidney damage with normal or increased GFR)

Stage 2: GFR 60 to 89 mL/min/1.73 m² (kidney damage with mild reduction of GFR)

Stage 3: GFR 20 to 59 mL/min/1.73 m² (moderate reduction of GFR)

Stage 4: GFR 15 to 29 mL/min/1.73 m² (severe reduction of GFR)

Stage 5: GFR <15 mL/min/1.73 m² or dialysis (kidney failure)

At stage 5, when end-stage renal disease develops, conservative management of chronic renal failure has been exhausted, and dialysis and transplantation become the next options for medical management.³¹

ETIOLOGY AND DIFFERENTIAL DIAGNOSIS

Congenital renal disease is the most common cause of chronic renal failure in young children, whereas glomerulonephritis and reflux nephropathy predominate in older children.³² Congenital structural lesions include dysplasias and cystic malformations (e.g., polycystic kidney disease). Obstructive uropathy leading to end-stage renal disease may be caused by posterior urethral valves in boys, severe vesicoureteral reflux with recurrent infection, and ureteropelvic junction obstruction. End-stage renal disease in children can be caused by hereditary nephritis or acquired nephropathies such as hemolytic-uremic syndrome, glomerulonephritis, and cortical necrosis (more common in children with sickle cell disease).

CLINICAL FEATURES

Take a complete history to obtain information about changes in urination, fatigue, swelling, anorexia, emesis, bone pain, muscle cramps, headache, and change in mental status. Ask about signs and symptoms related to potential complications from chronic kidney disease.

Complications associated with chronic kidney disease include disorders of fluids, electrolytes, and mineral metabolism. Anemia, hypertension, dyslipidemia, and endocrine abnormalities, including growth impairment, are present. End-stage renal disease is associated with cardiovascular problems and cerebrovascular events from malignant hypertension. Skeletal, hematologic, and intestinal abnormalities accompany renal failure. Renal failure predisposes to non-Hodgkin's lymphoma and skin cancer.^29,32

Pertinent physical findings in patients with end-stage renal disease include short stature, CNS problems, peripheral neuropathies, and rickets. Fever should prompt an aggressive search for a source. Fluid overload is suggested by peripheral edema and pulmonary congestion. Pericarditis is less common in children with end-stage renal disease than in adults. Abdominal pain and tenderness in children receiving peritoneal dialysis suggests peritonitis.

TREATMENT

The standard of treatment for most patients with end-stage renal disease is hemodialysis. Children <2 years of age are often treated with peritoneal dialysis because it is associated with fewer complications than hemodialysis in young children. Renal transplantation is the ultimate goal.^28,29,32

In dialysis patients presenting to the ED with fever, an aggressive search for infection must ensue. Use of empiric antibiotics is directed by the source of the infection (e.g., S. aureus, S. epidermidis), after cultures are drawn. If a patient on peritoneal dialysis presents with abdominal pain, suspect bacterial peritonitis. In patients presenting with severe electrolyte abnormalities, fluid overload, severe hypertension, or uremic pericarditis, urgent dialysis is indicated. Dialysis patients presenting with syncope should be evaluated for electrolyte abnormalities, hypovolemia, and cardiac dysrhythmias. See chapter 90, "End Stage Renal Disease" in the adult section for detailed discussion.