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CHAPTER 137: Renal Emergencies in Children 881 Renal Emergencies in Children Andrew Dixon Brandy Stauffer ACUTE KIDNEY INJURY 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 mani fested 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, it can be removed by dialysis, and variable cutoff values for creatinine have been used in AKI. 3 Therefore, the international classification system, Kidney Disease: Improving Global Outcomes (Table 137-1), is preferred.4,5 The system uses creatinine and urine output criteria and can be applied to both children and adults, minimizing practice variation. 2-4 In neonates, baseline creatinine is influenced by maternal creatinine and clearance is decreased in premature kidneys. Suggested modifica tions to the Kidney Disease: Improving Global Outcomes Classification for neonates are listed in Table 137-1. AKI is common in critically ill children, with an incidence of 27% overall among children hospitalized for intensive care; 12% have severe AKI, and 1.5% require renal replacement therapy. 6,7 Among children admitted to non–intensive care settings, the incidence is approximately 5%. 8 While the incidence is highest among adolescents, it is also com mon in neonates, and more common in boys than girls. 9 The most common causes of AKI in developed countries include cardiac and oncologic disease and their complications as well as nephrotoxin expo sure, whereas sepsis, hypovolemia, and glomerulonephritis are common in the developing world. 3,10-12 Regardless of etiology, AKI is consistently associated with morbidity and mortality among survivors, as well as long-term loss of renal function. 3,12,13  PATHOPHYSIOLOGY AKI is the result of nephrotoxic and/or hypoxic injury to the glom eruli and renal tubules. Reduced blood flow causes hypoxic injury and damages the proximal tubular cells. Common nephrotoxins include aminoglycosides, contrast agents, calcineurin inhibitors, amphotericin B, NSAIDs, and cancer chemotherapeutics. 14,15 Inflammatory mediators intensify renal tubular damage. 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 com mon 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 fail ure, 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).

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. Inquire about urine output, hematuria, and edema, which are the most common symptoms noted in AKI from intrinsic renal disease. Other 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 (hemolyticuremic 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. 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. 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 (e.g., palpable bladder suggestive of obstruction) and organomegaly, which may indicate fluid overload in young children. Examine the skin for rashes (e.g., palpable purpura of Henoch-Schönlein purpura).  DIAGNOSIS Laboratory Evaluation AKI 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 AKI. In children who are not toilet trained, it may be necessary to obtain a urine specimen by catheterization. In pre renal 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 spe cific gravity is often high (>1.025) in prerenal AKI and may be normal to low in acute tubular necrosis. CHAPTER TABLE 137-1 KDIGO Classification of Renal Injury Stage* Lab Criteria Urine Output Criteria Other Criteria Neonatal Criteria I Serum creatinine 1.5–1.9 times baseline or increase of ≥0.3 milligram/dL Urine output <0.5 mL/kg/h for 6 h   Creatinine as per children. Urine output <0.5 mL/kg/h for 6–12 h II Serum creatinine 2–2.9 times baseline Urine output <0.5 mL/kg/h for 12 h   Creatinine as per children.

teria Other Criteria Neonatal Criteria I Serum creatinine 1.5–1.9 times baseline or increase of ≥0.3 milligram/dL Urine output <0.5 mL/kg/h for 6 h   Creatinine as per children. Urine output <0.5 mL/kg/h for 6–12 h II Serum creatinine 2–2.9 times baseline Urine output <0.5 mL/kg/h for 12 h   Creatinine as per children. Urine output <0.5 mL/kg/h for ≥12 h III Serum creatinine 3 times baseline or increase in serum creatinine to ≥4 milligrams/dL Urine output <0.3 mL/kg/h for 24 h or anuria for ≥12 h Initiation or renal replacement therapy Serum creatinine >3 times baseline or ≥2.5 milligrams/dL. Urine output as for children Abbreviation: KDIGO = Kidney Disease: Improving Global Outcomes. *Stage is determined by meeting any criterion (lab or urine output or other) in that row. Tintinalli_Sec12_p0669-0996.indd 881 8/2/19 7:56 PM

renal replacement therapy Serum creatinine >3 times baseline or ≥2.5 milligrams/dL. Urine output as for children Abbreviation: KDIGO = Kidney Disease: Improving Global Outcomes. *Stage is determined by meeting any criterion (lab or urine output or other) in that row. Tintinalli_Sec12_p0669-0996.indd 881 8/2/19 7:56 PM 882 SECTION 12: Pediatrics Obtain serum electrolyte levels, including calcium, magnesium, and phosphate, when AKI is suspected because hyperkalemia and other electrolyte abnormalities may require emergent treatment. Hyperkalemia may result from a combination of factors including reduced glomerular filtration rate, decreased tubular secretion of potassium, tissue break down 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 hypocalce mia. 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). Serum compliments (C3, C4, CH50) and serologic testing for streptococcal infections may be useful for immune-mediated AKI. 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. Imaging A chest radiograph can identify an increase in heart size or pulmonary edema. Renal US identifies anatomic abnormalities, hydro nephrosis, and/or hydroureter. Voiding cystourethrogram is obtained in boys with suspected posterior urethral valves. Additional imaging depends on the differential diagnosis.  TREATMENT Treatment of AKI 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. 16 Packed RBCs are transfused at a volume of 10 mL/kg. Fresh frozen plasma and platelets may be neces sary in massive hemorrhage (see Chapter 144, “Hematologic Emergen cies in Infants and Children”). In renal failure from intrinsic renal disease, the specific cause must be identified and treated. Depending on the clinical state, manage oli guria and fluid overload with fluid restriction, limiting replacements to insensible losses only. Diuretics may be helpful to reduce fluid overload but are less effective in children with AKI and may require higher than usual doses. 3,16 Discontinue all nephrotoxic medications or adjust dose for glomerular filtration rate. Treat hypertension with antihypertensive agents or diuretics (see later section “Hypertension”). Manage oliguria of postrenal failure with fluid restriction and treat ment of hypertension. A Foley catheter may be necessary to relieve the obstruction. In all types of AKI, electrolyte management is impor tant. Do not administer potassium or phosphorus to children with oligoanuric AKI unless symptomatic from hypokalemia or hypo phosphatemia. The management of life-threatening hyperkalemia and hyponatremia is discussed in Chapter 132, “Fluid and Electrolyte Therapy in Infants and Children.

electrolyte management is impor tant. Do not administer potassium or phosphorus to children with oligoanuric AKI unless symptomatic from hypokalemia or hypo phosphatemia. The management of life-threatening hyperkalemia and hyponatremia is discussed in Chapter 132, “Fluid and Electrolyte Therapy in Infants and Children. ” When conservative management fails, consider acute renal replace ment 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.  DISPOSITION AND FOLLOW-UP Although the primary care physician can manage mild renal insuffi ciency 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. Pediatric urology consultation is needed for postrenal failure.16 Admit children with severe electrolyte abnormalities and fluid overload to a pediatric intensive care unit. NEPHROTIC SYNDROME Nephrotic syndrome is a chronic disease in children that alters per meability at the glomerular capillary wall, which causes a urinary loss of protein. The disease is classically characterized by proteinuria (>40 milligrams/m 2 in 24 hours), hypoalbuminemia (serum albumin <25 grams/L), hyperlipidemia, and edema. 17,18 However, hyperlipidemia and edema are not consistently present. Nephrotic syndrome can be primary (involving only the kidney) or secondary (multisystem). Primary nephrotic syndrome accounts for 95% of pediatric nephrotic syndrome and is idiopathic in 80% to 90% of children age 2 to 8 years old, but is genetic in the vast majority of neonates and young infants. 17,19 The classification of primary nephrotic syndromes includes minimal change disease, focal segmental sclerosis, membranous nephropathy, membranoproliferative nephritis, and proliferative nephritis (diffuse, focal, or mesangial). Secondary nephrotic syndrome is rare in children, but can be caused by autoimmune disease (Henoch-Schönlein purpura, lupus, diabetes), infections (hepatitis, human immunodeficiency virus, malaria, parasites), drugs, diabetes, or malignancy. 17,18  PATHOPHYSIOLOGY When podocytes within the glomerular membrane are damaged by immune dysregulation or systemic circulating factors, the permeabil ity of the glomerulus to proteins normally not able to pass through the glomerular capillary wall is increased. 18 Increased permeability results in the two diagnostic hallmarks of nephrotic syndrome: pro teinuria 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 reninangiotensin-aldosterone system to increase distal sodium reabsorp tion, which exacerbates the cycle.  CLINICAL FEATURES History and Complications Edema is the most common complaint. Anasarca consists of marked peripheral edema, ascites, scrotal or vulvar edema, and severe periorbital edema. Shortness of breath, cough, and orthopnea suggest a pleural effusion. Ask about urine output, because oliguria is often associated with more severe edema. Nausea, vomit ing, and anorexia suggest ascites or edema of the bowel wall, and when accompanied by fever, raise concern for spontaneous bacterial peritonitis.

dema. Shortness of breath, cough, and orthopnea suggest a pleural effusion. Ask about urine output, because oliguria is often associated with more severe edema. Nausea, vomit ing, and anorexia suggest ascites or edema of the bowel wall, and when accompanied by fever, raise concern for spontaneous bacterial peritonitis. Review of systems should note fever, fatigue, arthralgias or arthritis, rash, and the volume and character of the urine (foamy, bloody, or tea colored). 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). 17,20 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. Hyper lipidemia may lead to hyperviscosity, and increased levels of fibrinolytic inhibitors increase thrombotic risks. Physical Examination Edema is the most common physical exam finding in nephrotic syndrome and is typically more prominent in the morning and in dependent areas. Rebound abdominal tenderness and ascites are other potential findings. 5 Auscultate for findings of pleural effusion and pulmonary edema. Examine the abdomen for signs of peritoneal fluid, and note tenderness or guarding, which may be signs of peritonitis. Be careful not to confuse facial swelling due to nephrotic syndrome with swelling secondary to allergic reaction. Tintinalli_Sec12_p0669-0996.indd 882 8/2/19 7:56 PM

eural effusion and pulmonary edema. Examine the abdomen for signs of peritoneal fluid, and note tenderness or guarding, which may be signs of peritonitis. Be careful not to confuse facial swelling due to nephrotic syndrome with swelling secondary to allergic reaction. Tintinalli_Sec12_p0669-0996.indd 882 8/2/19 7:56 PM CHAPTER 137: Renal Emergencies in Children 883  DIAGNOSIS The diagnostic criteria of nephrotic syndrome are as follows21: 1. Edema 2. Proteinuria: 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/m 3. Hypoalbuminemia: Serum albumin <25 grams/L Renal biopsy is not indicated during the initial episode of acute nephrotic syndrome. Early renal biopsy should be considered for infants with nephrotic syndrome; those with persistent elevation in serum cre atinine, hypocomplementemia, or gross hematuria; and those who are treatment resistant. 18,22 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, renal function tests, coagulation studies). 17 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 diag nosis 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 rehy dration with small, frequent aliquots of sodium-deficient solutions. Treat volume overload with sodium and fluid restriction and diuretics (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; membra nous nephropathy may respond to steroids; focal segmental sclerosis is typically steroid resistant. 23 When indicated, prednisone is often started at 2 milligrams/kg/d in two or three divided doses, or 60 milligrams/m 2 (maximum 60 milligrams/d). The duration of initial therapy and subsequent tapering vary across national guidelines, but often continue for weeks to months. 17,24-26 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 steroiddependent or steroid-resistant nephrotic syndrome, the nephrologist must be consulted for initiation of medications. Common second-line medications for refractory nephrotic syndrome include cyclosporine, cyclophosphamide, mycophenolate, tacrolimus, and rituximab.

in consultation with a pediatric nephrologist. In steroiddependent or steroid-resistant nephrotic syndrome, the nephrologist must be consulted for initiation of medications. Common second-line medications for refractory nephrotic syndrome include cyclosporine, cyclophosphamide, mycophenolate, tacrolimus, and rituximab. 17,18,22,26  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. 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. GLOMERULONEPHRITIS 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. Glomerulonephritis is caused by several disorders, all of which cause inflammation leading to glomerular injury. It can be caused by immune-mediated disorders, inherited disorders, or postinfectious sequelae. Examples of hereditary glomerular diseases include systemic lupus erythematosus nephritis, thin glomerular basement membrane disease, and Alport’s syndrome. Poststreptococcal glomerulonephritis, immunoglobulin A (IgA) nephropa thy, and Henoch-Schönlein purpura will be discussed in this section.  PATHOPHYSIOLOGY Glomerulonephritis is an inflammatory process affecting the glom erulus. 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. Glomerulonephritis may be classified as primary (isolated to the kid ney) or secondary (a result of a systemic disorder). There are four main presentations: acute glomerulonephritis, rapidly progressive glomeru lonephritis, 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.  CLINICAL FEATURES Hematuria is the most common symptom of glomerulonephritis but may be subclinical (microscopic). “Synpharyngitic” macroscopic hematuria refers to gross hematuria with concomitant pharyngitis and can be seen in IgA nephropathy. 27 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. Patients may complain of bloody or foamy urine (a result of proteinuria), oliguria, nausea, fatigue, or lethargy. 28 The physical examination is often normal.  LABORATORY EVALUATION In glomerulonephritis, the urinalysis demonstrates macroscopic or microscopic hematuria, RBC casts, and proteinuria. Microscopic examination of urinary sediment shows dysmorphic RBCs and RBC casts.

proteinuria), oliguria, nausea, fatigue, or lethargy. 28 The physical examination is often normal.  LABORATORY EVALUATION In glomerulonephritis, the urinalysis demonstrates macroscopic or microscopic hematuria, RBC casts, and proteinuria. Microscopic examination of urinary sediment shows 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. 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. 27,29,30 Consider streptococcal serologic tests (antistreptolysin-I and streptozyme). More specific tests may be needed to make a clear diagnosis in illnesses with systemic manifestations such as systemic lupus erythematosus. A renal biopsy is often required for definitive diagnosis in glomerulonephritic disorders.  POSTSTREPTOCOCCAL GLOMERULONEPHRITIS Poststreptococcal glomerulonephritis is caused by prior infection with group A β-hemolytic streptococci. Only certain strains of this group Tintinalli_Sec12_p0669-0996.indd 883 8/2/19 7:56 PM

renal biopsy is often required for definitive diagnosis in glomerulonephritic disorders.  POSTSTREPTOCOCCAL GLOMERULONEPHRITIS Poststreptococcal glomerulonephritis is caused by prior infection with group A β-hemolytic streptococci. Only certain strains of this group Tintinalli_Sec12_p0669-0996.indd 883 8/2/19 7:56 PM 884 SECTION 12: Pediatrics are “nephritogenic, ” and the pharynx and skin are the most common sites of infection leading to acute glomerulonephritis, occurring 7 to 15 days after pharyngitis and 3 to 5 weeks after skin infection. 31 Group A β-hemolytic streptococci stimulate immune complex formation sec ondary to deposition of streptococcal nephritogenic antigens within the glomerulus. Other infections such as Staphylococcus aureus and Staphylococcus epidermidis may also lead to renal disease, usually with a longer latency period. Clinically, poststreptococcal glomerulonephritis consists of micro scopic 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 anti–streptolysin O or anti–DNAse B titers (or the combined streptozyme test), which are typically elevated, and a serum C3 level, which is typically decreased. Treatment is largely supportive. Symptoms of poststreptococcal glo merulonephritis usually resolve in a few weeks. Hypertension rarely requires long-term treatment and tends to resolve within 1 to 2 weeks. Renal biopsy is not indicated for diagnosis, unless atypical clinical fea tures are present. 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 and is the most common single cause of glomerulonephritis worldwide. 27 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: mac roscopic 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 (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 (e.g., corti costeroids) may be initiated to treat underlying inflammation, depend ing on disease severity. Angiotensin-converting enzyme inhibitors or angiotensin receptor blockers may be used to control blood pressure, particularly in patients with proteinuria. IgA nephropathy can either completely resolve or progress to end-stage renal disease. 27 Concern for IgA nephropathy in the ED warrants an outpatient referral to nephrol ogy. 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.

ociated 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. Renal complications occur in 20% to 54% of patients with Henoch-Schönlein purpura and include gross or microscopic hematuria, proteinuria, or nephritic syndrome. 32,33 Of the children diagnosed with Henoch-Schönlein purpura, 40% have mild nephritis, manifested only by microscopic hematuria or low-grade proteinuria. Risk factors for the development of renal complications include male gender, age >10 years, abdominal pain, GI bleeding, persistent purpura, elevated anti–streptolysin O, WBC >15,000/mm 3, and platelets >500 × 10 9/L.34 Renal complications may develop any time over a period of 28 days, and 2% of children may develop long-term renal impairment. 35 Obtain a urinalysis to identify RBCs, casts, and protein. Treatment focuses on hydration, rest, and analgesics. Although corticosteroids may provide symptomatic relief for severe abdominal pain, they do not prevent renal involvement or long-term renal damage and are not recommended . 36,37 Further discussion of Henoch-Schönlein purpura can be found in Chapter 133, “ Acute Abdominal Pain in Infants and Children, ” and Chapter 142, “Rashes in Infants and Children. ”  HEMOLYTIC-UREMIC SYNDROME Hemolytic-uremic syndrome is a multisystem disorder resulting in AKI, 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 bloody diarrhea; 10% to 15% of children with Shiga toxin–producing E. coli develop hemolytic-uremic syndrome (see Chapter 131, “Vomiting, Diarrhea, and Dehydration in Infants and Children”). 38,39 Other causes of hemolytic-uremic syndrome are S. pneumoniae infection, genetic disorders, oral contraceptive use, pregnancy, and malignancy. Despite widespread immunization for S. pneumoniae , the incidence of hemolytic-uremic syndrome associ ated with invasive disease has not decreased, and nonvaccine strains have replaced vaccine strains in these cases. 40 Mortality and severe renal involvement are higher in S. pneumoniae–associated hemolyticuremic syndrome than typical Shiga toxin–producing E. coli associated disease. 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 endothelial damage and leading to microangiopathic intravascular thrombosis, RBC hemolysis, thrombocytopenia (due to platelet consumption), and decreased glomerular perfusion. 41 Microthrombi are deposited in kidney parenchyma, causing hypertension, oliguria, and anuria. Renal involvement ranges from mild renal insufficiency to AKI requiring dialysis. In atypical hemolytic-uremic syndrome associated with S. pneumoniae (5% of cases), 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.

ogenesis 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. 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 of the resolution of the GI symptoms, pallor, edema, oliguria, shortness of breath, and seizures or encephalopathy develop. S. pneumoniae –associated hemolytic-uremic syndrome can accompany severe invasive disease, typically in the setting of pneumonia, sepsis, or meningitis. Other com plications include hypertension, heart failure, intussusception, diabetes mellitus, acidosis, and colitis. 39 A careful dietary and travel history may identify a potential source of infection to aid public health officials assess epidemic outbreaks. Laboratory Evaluation Obtain a CBC and peripheral smear; micro angiopathic hemolytic anemia, one of the cardinal features of hemolyticuremic syndrome, may be profound with a hemoglobin level between 5 and 9 grams/dL; the smear demonstrates schistocytes, helmet cells, and burr cells. The platelet count is <150,000/mm 3. The WBC count may be elevated (poor prognosis). If obtained, the Coombs test is negative. Check electrolytes and renal and hepatic function; hyponatremia and hyperkalemia develop as a result of metabolic acidosis from renal failure, and hyperbilirubinemia results from acute hemolysis. Send a stool specimen for culture and to test for Shiga toxin. Uri nalysis demonstrates gross or microscopic hematuria with granular and hyaline casts and variable proteinuria and leukocyturia. Treatment ED management is supportive, although some studies suggest that early aggressive volume expansion (in the absence of signs of fluid overload), may improve outcomes in typical hemolytic-uremic syndrome. 42,43 Correct life-threatening electrolyte disturbances and Tintinalli_Sec12_p0669-0996.indd 884 8/2/19 7:56 PM

atment ED management is supportive, although some studies suggest that early aggressive volume expansion (in the absence of signs of fluid overload), may improve outcomes in typical hemolytic-uremic syndrome. 42,43 Correct life-threatening electrolyte disturbances and Tintinalli_Sec12_p0669-0996.indd 884 8/2/19 7:56 PM CHAPTER 137: Renal Emergencies in Children 885 TABLE 137-2 Laboratory Findings in Renal Tubular Acidosis (RTA) Type of RTA Plasma Anion Gap Urinary Anion Gap Serum Potassium Minimal Urine pH (in the presence of acidosis) Additional Laboratory Tests Distal or type I RTA Normal Elevated Normal or low >5.5 Arterial blood gas concentrations, urine pH (>5.3), urine calcium/creatinine ratio elevated Proximal or type II RTA Normal Normal Normal or low <5.5 Arterial blood gas concentrations, urine pH (>5.5, except in severe metabolic acidosis), serum K level, fractional excretion of HCO Type IV RTA Normal Elevated High <5.5 Arterial blood gas concentrations, urine pH (<5.5 with severe metabolic acidosis), urine to blood co2, creatinine clearance TABLE 137-3 Definition of Elevated Blood Pressure and Hypertension in Children Age 1 to <13 y* Age ≥13 y Elevated blood pressure ≥90th to <95th percentile or 120/80 mm Hg to <95th percentile 120/<80 to 129/<80 mm Hg Stage I hypertension ≥95th to <95th percentile + 12 mm Hg or 130/80 to 139/89 mm Hg 130/80 to 139/89 mm Hg Stage II hypertension ≥95th percentile + 12 mm Hg or ≥140/90 mm Hg ≥140/90 mm Hg *Use lower value. treat hypovolemia with IV fluid boluses (10 to 20 mL/kg normal saline). Antibiotics are contraindicated in pediatric diarrheal illness and may increase the risk hemolytic-uremic syndrome. 44 Antiperistaltic agents increase the risk for systemic complications associated with E. coli infection and are also contraindicated. Blood transfusions may be needed for severe anemia. Platelet transfusion is not recommended because it could worsen the thrombotic process. Treatment with eculi zumab or plasma exchange may be helpful. 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 approximately half of cases of acute hemolytic-uremic syn drome.39 Most children (95%) survive the acute phase of the illness, and most regain normal renal function. RENAL TUBULAR ACIDOSIS 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 glomerular filtration rate. In children, renal tubular acidosis is typically secondary to an inher ited or acquired defect that affects the kidney’s ability to manage bicarbonate, acid, and ammonia. Renal tubular acidosis develops because of impaired distal acidification (type I), reduced proximal bicarbonate reabsorption (type II), or reduced production of ammonium from aldosterone deficiency or resistance (type IV). For example, Fanconi’s syndrome causes a type II renal tubular acidosis and may be associ ated with hypophosphatemia and rickets. Types I and II renal tubular acidosis result in hyperchloremic metabolic acidosis with hypokalemia, whereas type IV renal tubular acidosis results in hyperkalemia, acidemia, and a low urinary pH; the metabolic acidosis has a normal anion gap in all types. 45,46 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 hyper kalemia (weakness, nausea, constipation), rickets, or nephrolithiasis may prompt an ED visit.

ren 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 hyper kalemia (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 137-2 describes the typical laboratory findings in each type of renal tubular acidosis. 45,46 Acute treatment consists of correcting the underlying electrolyte and acid-base abnormalities. 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 mineralo corticoid deficiency in type IV renal tubular acidosis.  HYPERTENSION Pediatric hypertension is increasing in incidence, with prevalence esti mates ranging from 0.3% to 4.5% in children.48,49 This increase is related to higher rates of childhood obesity, greater salt intake, hyperlipidemia, and decreased physical activity. 48 Boys, adolescents, and Hispanic and African American race are associated with higher rates of hypertension in the United States. 49 The definition of hypertension in children has undergone several revisions, and the latest guidelines from the American Academy of Pediatrics (2017) are summarized in Table 137-3. Traditionally, hypertensive urgency was a severely elevated blood pressure without evidence of target organ damage that, left untreated, may cause end-organ damage, whereas hypertensive emergency was defined as blood pressures exceeding the 99th percentile for age and sex with acute end-organ damage that requires immediate treatment. With the updated American Academy of Pediatrics practice guidelines mentioned earlier, the term acute severe hypertension was suggested to describe any acute symptomatic presentation of hypertension. 49 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. 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), abnor mal 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 137-4 outlines the common causes of hypertension by age group.  CLINICAL FEATURES Children with hypertensive crisis range from having mild symptoms such as headache, nausea, vomiting, visual changes, and anxiety to life-threatening encephalopathy or focal neurologic deficits, chest pain and shortness of breath from acute heart failure and pulmonary edema, and anuria from AKI. In neonates and young infants, feeding problems, Tintinalli_Sec12_p0669-0996.indd 885 8/2/19 7:56 PM

dache, nausea, vomiting, visual changes, and anxiety to life-threatening encephalopathy or focal neurologic deficits, chest pain and shortness of breath from acute heart failure and pulmonary edema, and anuria from AKI. In neonates and young infants, feeding problems, Tintinalli_Sec12_p0669-0996.indd 885 8/2/19 7:56 PM 886 SECTION 12: Pediatrics TABLE 137-4 Common Causes of Hypertension in Children Age Group Cause Newborn Renal: thrombosis, stenosis, polycystic kidney disease Heart: coarctation of the aorta Endocrine: pheochromocytoma, Cushing’s disease Preschool/kindergarten (<6 y) Renal: parenchymal disease, vascular disease Heart: coarctation of the aorta Endocrine: pheochromocytoma, Cushing’s disease School age (6–10 y) Endocrine: pheochromocytoma, Cushing’s disease, thyrotoxicosis Adolescence Essential hypertension (especially in obese adolescents) Renal: parenchymal, vascular Endocrine: pheochromocytoma, Cushing’s disease, thyrotoxicosis Drugs of abuse (e.g., cocaine, amphetamines), NSAIDs, monoamine oxidase inhibitors, steroids, calcineurin inhibitors (cyclosporin/tacrolimus) TABLE 137-5 Oral Antihypertensives for Hypertensive Urgency in Infants and Children Drug Class Dosage Route Onset of Action Comments Isradipine Calcium channel blocker 0.05–0.1 milligram/kg/dose up to 5 milligrams/dose PO 2–3 h Tachycardia, headache Caution in those taking azole antifungals (hypotension) Nifedipine Calcium channel blocker 0.1–0.25 milligram/kg/dose PO, sublingual Immediate release, 20–30 min Extended release, 2.5–5 h Precipitous drop in blood pressure, tachycardia, headache Minoxidil Vasodilator 0.1–0.2 milligram/kg/dose PO Within 30 min Fluid retention Doxazosin α-Blocker 1–2 milligrams/kg per dose PO 2–6 h Dizziness, orthostatic hypotension Useful in hyperadrenergic states (e.g., pheochromocytoma) Prazosin α-Blocker 0.02–0.04 milligram/kg/dose PO 30–90 min Dizziness, headache Useful in hyperadrenergic states (e.g., pheochromocytoma) Clonidine Central α-agonist 2–10 micrograms/kg/dose every 6–8 h PO 30–60 min Rebound hypertension, sedation, dry mouth Captopril Angiotensin-converting enzyme inhibitor 0.1–0.2 milligram/kg/dose 0.01–0.1 milligram/kg/dose in neonates PO 10–20 min Contraindicated in bilateral renal artery stenosis; not recommended in acute or chronic renal failure irritability or lethargy, respiratory distress, or seizures may be manifestations of a hypertensive crisis. History and Comorbidities Obtain a detailed history of symptoms that suggest end-organ damage including neurologic symptoms, chest pain, shortness of breath, decreased urine output, or hematuria, as described earlier. Other symptoms may help to identify an underlying cause such as palpitations, weight loss, flushing, and diarrhea, which point to an endocrine disorder. Identify any medications or substances associated with blood pressure elevation, such as oral contraceptives, steroids, immunosuppressants, and illicit drugs (e.g., cocaine, amphetamines). Ask about a family history of essential hypertension, diabetes, obesity, renal disease, hyperlipidemia, stroke, or endocrinopathy. For those with an established diagnosis of hypertension, ask about medica tion adherence or abrupt withdrawal. Physical Examination Obtain an accurate height and weight and determine percentiles for age. Obtain four-limb blood pressures in infants (a lower blood pressure in the lower extremities compared to the upper extremities or left versus right arms may indicate aortic coarcta tion). Perform a comprehensive physical examination, including a fun duscopic examination (for retinal hemorrhages, papilledema, infarcts) and a neurologic examination. Assess the heart and lungs for signs of congestive heart failure or structural disease (gallops, murmurs, rales).

ight arms may indicate aortic coarcta tion). Perform a comprehensive physical examination, including a fun duscopic examination (for retinal hemorrhages, papilledema, infarcts) and a neurologic examination. 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. Obtain a CBC and reticulocyte count to look for rheumatic disorders, appropriate marrow response, and signs of anemia. Perform a pregnancy test in pubertal girls. Ordering of more esoteric tests for endocrine abnormalities should be left to subspecialists. Imaging Obtain a chest radiograph and ECG. Obtain an echocardio gram to look for left ventricular hypertrophy and to rule out cardiac causes of hypertension. Obtain a head CT if neurologic findings are present. Renal US is indicated to rule out structural kidney abnormali ties. If suspicion for renovascular disease is high, then obtain a CT angiography or magnetic resonance angiography.  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 (Table 137-5). 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 6 to 8 hours, followed by a gradual reduction to normal values over the next 26 to 48 hours toward the 95th percentile for age. 50 Reducing the blood pressure too aggressively can lead to isch emic complications such as acute neurologic issues, blindness, and renal failure. Recommendations regarding the most useful drugs for treating severe hypertensive emergency in children are listed in Table 137-6. Medications should be chosen according to their side effect profile, availability, and physician familiarity, as there are limited clinical data in children and infants.  DISPOSITION AND FOLLOW-UP Mild hypertension should be managed on an outpatient basis by the primary care provider or subspecialist. Hypertensive urgencies and emer gencies 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. Tintinalli_Sec12_p0669-0996.indd 886 8/2/19 7:56 PM

. Hypertensive urgencies and emer gencies 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. Tintinalli_Sec12_p0669-0996.indd 886 8/2/19 7:56 PM CHAPTER 137: Renal Emergencies in Children 887 TABLE 137-6 Parenteral Antihypertensives for Hypertensive Crisis in Infants and Children Drug Class Dosage Route Onset Comments Nitroprusside Vasodilator 0.5–8.0 micrograms/kg/min IV infusion IV infusion Seconds May increase intracranial pressure. Monitor cyanide and thiocyanate levels for patients with renal and liver disease when administering for >24–48 h. Hydralazine Vasodilator 0.1–0.5 milligram/kg/dose; maximum, 20 milligrams/dose IV, IM 5–30 min Administer every 4 h when given as IV bolus. Not as strong as other agents. Recommended dose is less than U.S. Food and Drug Administration–approved label. Reflex tachycardia Diazoxide Vasodilator 1–3 milligrams/kg every 5–15 min IV bolus Within minutes Risk of hypotension Nicardipine Calcium channel blocker 1.0–3.0 micrograms/kg/min IV infusion IV infusion Within minutes May cause increased intracranial pressure, headache, nausea, and hypotension Labetalol α- and β-blocker Bolus: 0.2–1.0 milligram/kg/dose to a maximum of 40 milligrams/dose, then infusion: 0.25–3.0 milligrams/kg/h IV bolus or infusion 2–5 min Contraindications include asthma, chronic lung disease, and evident heart failure; may mask hypoglycemic symptoms Urapidil α 1-Blocker and central 5-HT1A agonist Initial dose 0.5–4.0 milligrams/kg/h Maintenance dose 0.2–2.0 milligrams/kg/h IV infusion 1–5 min Contraindicated in aortic stenosis; palpitations, nausea, sedation Esmolol β-Blocker 100–500 micrograms/kg/min (initial dose), then 50–300 micrograms/kg/min IV infusion Immediate May cause bronchospasm, congestive heart failure, and profound bradycardia Fenoldopam Dopamine receptor agonist 0.2–0.8 microgram/kg/min IV infusion Within minutes Tachycardia, flushing, headache Furosemide Loop diuretic 0.5–5 milligrams/kg/dose IV bolus Within minutes Useful for volume overload hypertension; may cause hypokalemia Diazoxide Vasodilator 1–3 milligrams/kg every 5–15 min IV bolus Within minutes Risk of hypotension HEMATURIA 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, 51 idiopathic hypercalciuria, IgA nephropathy, Alport’s syndrome, and sickle cell trait or anemia or with drugs or toxins.52  CLINICAL FEATURES History and Comorbidities Obtain a complete history, because the differential diagnosis is broad. Distinguish between transient, persistent, and recurrent hematuria. 53 Associated dysuria, urinary frequency and urgency, fever, and abdominal or flank pain suggest infection or uroli thiasis (see Chapter 94, “Urologic Stone Disease”). A history of an upper respiratory tract infection, sore throat, or skin infection may suggest postinfectious glomerulonephritis. A current infectious process is sus picious for IgA nephropathy. For transient hematuria, ask about blunt abdominal trauma, recent catheterization, or menstruation.

“Urologic Stone Disease”). A history of an upper respiratory tract infection, sore throat, or skin infection may suggest postinfectious glomerulonephritis. A current infectious process is sus picious for IgA nephropathy. For transient hematuria, ask about blunt abdominal trauma, recent catheterization, or menstruation. 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, pos terior urethra, or prostate)—provide useful diagnostic information. Ask about joint pain and rash (Henoch-Schönlein purpura or lupus). Some drugs associated with hematuria are NSAIDs, anticonvulsants, warfarin, diuretics, penicillin, and chlorpromazine. Recent vigorous exercise can cause hematuria, which resolves after a period of rest. Obtain a fam ily 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. 53 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 informa tion. 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, rifampin, isoniazid, malin, and nitrofurantoin may cause a red-brown discoloration of the urine. 53 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. 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 hema turia without proteinuria or RBC casts in the urine and is done to rule out malignancy or structural defects. For patients with trauma or Tintinalli_Sec12_p0669-0996.indd 887 8/2/19 7:56 PM