Answers
Board Review
Renal Disorders -2
Question 241
You are evaluating a 15-year-old girl in your office for her annual health supervision visit. She is doing well in school and has no complaints about her health, although she would like to lose weight. She has joined the cross-country running team at school. She is not receiving any prescription medications but occasionally uses over-the-counter (OTC) cold remedies and vitamins. On physical examination, she appears thin but is in no distress. Both her height and weight are at the 25th percentile for her age, although her weight has decreased from the 50th percentile 1 year ago. Her heart rate is 100 beats/min and blood pressure is 145/95 mm Hg. Other findings on physical examination are normal.
Of the following, the MOST appropriate next step is to
answer D
Hypertension may be caused by medications, including over-the-counter preparations, dietary supplements, and illicit drugs. Essential, or primary, hypertension has no identifiable cause, but secondary hypertension results from an underlying condition, disorder, drug, or other stimulus. Among the agents that can cause hypertension are corticosteroids, estrogens such as those in contraceptive therapy, migraine medications, nasal decongestants, and cyclosporine. Over-the-counter preparations that can be associated with hypertension include the many medications used for relief of cough, cold, and runny nose. Substances of abuse that can cause hypertension include alcohol, amphetamines, cocaine, and Ecstasy (MDMA and its derivatives).
The patient described in the vignette has tachycardia and hypertension, with both the systolic and diastolic pressures being higher than the 95th percentile. Other important findings in the history include a relative weight loss from the 50th percentile at age 14 to the 25th percentile (3.5 kg/7 lb) at age 15 years. It is essential to obtain more detailed information regarding the family history, past medical conditions, hospitalizations, and medication use. The patient confirms the use of over-the-counter cold remedies, some of which are known to be associated with hypertension as well as vitamins. She should be asked for further information about these substances.
Because this is her first documented episode of hypertension, neither an evaluation for pheochromocytoma nor computed tomography scan of the abdomen is warranted. Without further information regarding her dietary habits, there is no indication that she has anorexia nervosa. Similarly, findings on the history are not suggestive of the muscularization or other physical changes that can be associated with anabolic steroid use.
Question 253
A 3-month-old boy is admitted to the hospital for evaluation of failure to thrive. His birthweight was at the 50th percentile and length at the 75th percentile. Currently, his weight is below the 5th percentile and length is at the 25th percentile. His vital signs and physical examination results are otherwise normal. He appears well hydrated. Measurement of serum electrolytes reveals: sodium, 139 mEq/L (139 mmol/L); potassium, 4.7 mEq/L (4.7 mmol/L); chloride, 114 mEq/L (114 mmol/L); bicarbonate 12 mEq/L (12 mmol/L); blood urea nitrogen, 8 mg/dL (2.9 mmol/L); and creatinine, 0.3 mg/dL (26.5 mcmol/L). A consulting nephrologist recommends measurement of urine pH (which is 7.5) and urine ammonium (which is 12,000 mcM/L) (normal,>60,000 mcM/L).
Of the following, the MOST likely cause of this child's acidosis is
answer C
The infant described in the vignette presents with failure to thrive, and measurement of his serum electrolytes reveals a normal anion gap and hyperchloremic metabolic acidosis. The key element in his presentation is the urine pH, which is 7.5, indicating that it is highly alkaline. In proximal renal tubular acidosis (RTA), as the urine leaves the proximal tubule, the relative inability to reabsorb bicarbonate results in a very alkaline pH of the tubular fluid. However, the distal tubule in patients who have proximal RTA is healthy, and it extrudes high quantities of acid, dropping the tubular pH to a lower value (=6.0). In contrast, because the distal nephron represents the last real opportunity for the kidney to regulate acid-base balance, children who have distal RTA cannot adequately compensate for the lack of acid extrusion, resulting in very alkaline urine. The urine ammonium value in the child in the vignette is very low at 12,000 mcM/L (normal >60,000 mcM/L), which is consistent with reduced acid (as part of ammonium) secretion and strongly predictive of distal RTA.
RTA is a common cause of metabolic acidosis in childhood. There are two primary types of RTA: proximal or type II and distal or type I. Type IV RTA, also called hyperkalemic RTA, is uncommon and will be discussed only briefly.
A review of basic renal physiology in the maintenance of acid-base balance is necessary to understand RTA. The primary responsibility of the proximal tubule in the preservation of normal acid-base homeostasis is to reabsorb filtered bicarbonate. It achieves this goal by reabsorbing water and carbon dioxide from the renal (apical membrane) tubule into the cell and then converting them to hydrogen and bicarbonate within the cell. Hydrogen is extruded back into the tubule, and bicarbonate is reabsorbed at the other end (basolateral membrane) of the cell. Thus, the reabsorption of base (bicarbonate) is linked with the expulsion of acid (hydrogen). In contrast, the primary role of the distal tubule is to secrete acid, either as free hydrogen ion, as part of ammonium (ammonia plus hydrogen), or linked to phosphorous. The distal nephron does play a role in bicarbonate reabsorption, but its primary role is to secrete acid.
Because children who have proximal (type II) RTA have difficulty reabsorbing bicarbonate, the serum bicarbonate concentration falls, resulting in acidosis. In distal (type I) RTA, the distal tubule struggles to secrete acid. This excess acid must be buffered in the blood, principally by bicarbonate, which also results in a decline in the serum bicarbonate or acidosis. In distal RTA, there may be concomitant proximal tubule disturbances. The level of the serum bicarbonate in either proximal or distal RTA may vary, depending on the extent of the deficit. To maintain electroneutrality in RTA, the loss of bicarbonate is compensated by the retention of chloride, also a negatively charged ion. Thus, the anion gap ([sodium]-[chloride + bicarbonate]) is maintained at 10 to 16. In other types of acidosis, such as lactic acidosis, the excess accumulation of acid does not induce an increase in chloride absorption and, thus, the anion gap is elevated.
Given the normal anion gap, this child cannot have either an inborn error of metabolism or lactic acidosis, which typically results in a high (>16) anion gap. Additionally, the normal serum potassium value effectively eliminates type IV RTA as a cause of the acidosis because the lack of aldosterone or renal resistance to aldosterone in this condition induces acidosis and hyperkalemia.
Question 205
A 10-year-old girl presents to the emergency department with a 1-day history of brown urine. She reports no dysuria, urgency, frequency, or abdominal or flank pain. Her vital signs include: temperature, 98.8°F (37.1°C); blood pressure, 165/97 mm Hg; heart rate, 84 beats/min; and respiratory rate, 20 breaths/min. On physical examination, moderate periorbital edema is evident, but there are no other abnormalities. Urinalysis reveals moderate blood and 4+ protein. The serum complement 3 (C3) concentration is low, and the C4 concentration is normal.
Of the following, the MOST likely cause of this girl's hematuria is
answer E
The girl in the vignette has painless gross hematuria without fever. Fever would suggest possible infection, and abdominal pain would hint at infection, stone, or renal malformation (tumor, cyst). She has an elevated blood pressure and periorbital edema, which may be due to hypoalbuminemia or fluid retention. Her urinalysis shows blood and protein. The most significant clue to the cause of her renal disease is her low serum complement 3 (C3) concentration and normal C4 concentration. She has strong evidence of nephritis (gross hematuria, hypertension, periorbital edema), decreased C3, and normal C4 values, which are consistent with postinfectious acute glomerulonephritis (PIAGN). If both the C3 and C4 values were low, the nephritis more likely would be membranoproliferative GN or lupus nephritis. Children who have either focal segmental glomerulosclerosis or immunoglobulin A nephropathy may develop gross hematuria, hypertension, edema, and nephritis, but because of the pathogenesis of these diseases, the serum complement values would be normal.
PIAGN is a common but generally self-limited renal disease that usually occurs in childhood. Among the several known pathogenetic organisms associated with PIAGN, the most common is group A beta-hemolytic Streptococcus. Most children who have PIAGN recover complete renal function and exhibit normalization of C3 levels by 6 weeks, although some continue to exhibit hematuria and/or proteinuria for prolonged periods after initial presentation. Some also have hypertension, primarily due to salt and water retention, for up to 3 months. Occasionally, the disease may assume a rapidly progressive course, resulting in acute renal failure and the need for treatment with high-dose intravenous corticosteroids and possibly intravenous cyclophosphamide or dialysis if renal failure persists. In these patients, the renal outcome is guarded.
Question 248
A mother brings in her 4-year-old son because his eyelids are swollen. On physical examination, the boy has normal growth parameters, normal blood pressure, bilateral periorbital edema (Item Q248A), and pitting pretibial edema. Laboratory findings include normal electrolyte concentrations, blood urea nitrogen of 14 mg/dL (5 mmol/L), creatinine of 0.3 mg/dL (26.5 mcmol/L), albumin of 1.9 g/dL (19 g/L), and normal C3 and C4 complement values. Urinalysis reveals a specific gravity of 1.030, pH of 6.5, 4+ protein, and 1+ blood, and microscopy demonstrates 5 to 10 red blood cells/high-power field. Antinuclear antibody test results are negative, and serologic tests are negative for hepatitis B surface antigen, negative for hepatitis C, and nonreactive for human immunodeficiency virus. A purified protein derivative test is nonreactive after 48 hours.
Of the following, the MOST appropriate treatment for this patient is:
answer D
The boy described in the vignette has new-onset nephrotic syndrome (NS). The first important step is to establish the diagnosis based on the presence of severe proteinuria, hypoalbuminemia, and edema. Next, the practitioner must note the child?s blood pressure (BP) and assess renal function by measuring a serum creatinine because mild degrees of BP elevation and mild azotemia are consistent with NS, but marked elevations of BP or creatinine are not. In addition, approximately 20% of children presenting with new-onset NS have microscopic hematuria; gross hematuria should not be present.
The next phase of the evaluation involves screening for secondary causes of NS. Typically, a serologic evaluation includes measurement of complement components (C3 and C4), antinuclear antibody, anti-double-stranded DNA, hepatitis B surface antigen and core antibody, hepatitis C antibody, and human immunodeficiency virus antibody. A complete blood count is obtained to look for hematologic abnormalities associated with NS, such as leukemia/lymphoma or sickle cell disease. A purified protein derivative test is placed to look for occult tuberculosis infection prior to starting treatment. If no secondary cause of the NS is identified by these tests, the treatment of choice is oral prednisone beginning at 60 mg/m2 per day in divided doses (maximum dose, 40 mg twice per day). The duration of daily therapy is 4 to 6 weeks, after which time the dose is reduced to 40 mg/m2 (maximum daily dose, 60 mg) on alternate days for 4 to 6 weeks. Recent studies suggest that a longer course (6 weeks daily followed by 6 weeks alternate-day) results in a higher sustained remission rate than a shorter course (4 weeks daily followed by 4 weeks alternate-day).
Although a low-sodium diet is recommended for children who have new-onset NS, it is adjunctive, not definitive therapy. Diuretics such as furosemide are not recommended in patients who have NS due to an increased risk of thrombosis. A protein-rich diet has no role in the treatment of NS because the hypoalbuminemia is due to glomerular losses, not malnutrition. Although allergies can cause periorbital swelling and may be treated with an antihistamine such as diphenydramine, patients typically exhibit other symptoms, such as rhinitis, sneezing, or conjunctival injection. If uncertainty exists as to the cause of periorbital swelling and there is concern about possible NS, performance of a urinalysis to detect proteinuria may be useful.
Question 218
A mother brings in her 3-year-old daughter because of daytime urinary incontinence and abdominal pain. The mother explained that the girl was toilet trained at 2 years of age. On physical examination, growth parameters and vital signs are normal, although the girl has mild suprapubic tenderness without associated costovertebral angle tenderness or sacral dimples. Urinalysis shows a urine specific gravity of 1.025, pH of 6.5, 2+ blood, 1+ protein, 3+ leukocyte esterase, and positive nitrite. Urine microscopy demonstrates 5 to 10 red blood cells/high-power field, 20 to 50 white blood cells/high-power field, and 3+ bacteria.
Of the following, the MOST likely etiologic agent is
Answer B
Escherichia coli is the causative organism in 80% to 90% of first-time urinary tract infections (UTIs) in children. Other pathogens include Klebsiella pneumonia, Proteus sp, Enterococcus sp, and Staphyloccus saprophyticus. Pseudomonas also can be a pathogen in immunocompromised patients or those who have received repeated courses of antibiotics for recurrent infections. The clinician must assess the patient for a UTI based on signs, symptoms, and urinalysis findings.
Organisms such as E coli, K pneumoniae, and Proteus sp can reduce dietary nitrate to nitrite, so a positive urine dipstick test for nitrite, as reported for the girl in the vignette, is virtually diagnostic of gram-negative bacteruria. If the test result is negative in an older child in whom a UTI is suspected, the infection may be caused by a gram-positive organism such as Enterococcus sp or S saprophyticus. Of note, the nitrite test is much less helpful in infants. Conversion of nitrate to nitrite may take up to 4 hours. Because infants and young children have small bladder volumes and urinate frequently, there may be insufficient time for nitrites to be formed and, therefore, the nitrite test may be negative even in the presence of a UTI caused by a gram-negative organism.
Urine pH also may be useful in diagnosing UTIs. Urease-producing organisms (eg, Proteus mirabilis, some strains of S saprophyticus) degrade urea into ammonia, resulting in an elevated urine pH (8.0 to 8.5).
The girl described in the vignette has symptoms of a lower UTI. Options for therapy include trimethoprim-sulfamethoxazole (if local resistance patterns indicate low levels of E coli resistance) or a third-generation cephalosporin (eg, cefixime, cefdinir). These antibiotics also may be used for outpatient management of acute pyelonephritis. For hospitalized patients, a third-generation cephalosporin such as ceftriaxone or cefotaxime provides adequate coverage. An alternative regimen is ampicillin plus gentamicin.
Question 94
A 6-year-old boy presents with cola-colored urine. His mother reports that he had a sore throat 10 days ago. On physical examination, his blood pressure is 136/88 mm Hg, and he has mild swelling of the face and lower extremities.
Of the following, the MOST likely laboratory finding is
answer A
The findings of cola-colored urine, swelling, and hypertension described for the boy in the vignette suggest the diagnosis of acute glomerulonephritis. The "sore throat" 10 days earlier makes acute poststreptococcal glomerulonephritis (APSGN) the most likely diagnosis. The initial assessment of a child in whom ASPGN is suspected must include measurement of blood pressure and serum creatinine to assess disease severity. Both severe hypertension and renal failure can occur as part of a rapidly progressive glomerulonephritis. After initial assessment, the most important diagnostic test is measurement of complement component 3 (C3) to confirm the presence of hypocomplementemia, which occurs in more than 90% of cases.
ASPGN is an immune complex-mediated glomerulonephritis that follows an infection by a nephritogenic strain of group A beta-hemolytic Streptococcus of the pharynx or skin. The interval between pharyngitis and the development of APSGN is approximately 1 to 2 weeks. In contrast, the latency period between a skin infection and ASPGN is 3 to 6 weeks. Most patients who have nephritis have a subclinical infection, which is estimated to occur four to five times more frequently than overt disease. APSGN in children is characterized by hematuria (100%), proteinuria (80%), edema (90%), hypertension (70%), and azotemia (33%). Thus, the urinalysis will not be normal. In addition, gross hematuria occurs in approximately 40% of children who have overt disease.
As noted previously, the characteristic laboratory feature of ASPGN is hypocomplementemia, which typically features depressed C3 and normal C4 values. The differential diagnosis of hypocomplementemic glomerulonephritis consists of membranoproliferative glomerulonephritis (MPGN) in a child who has disease limited to the kidney and systemic lupus erythematosus in a child who has multisystem disease. Rarer causes of hypocomplementemic glomerulonephritis include subacute bacterial endocarditis, shunt nephritis (in patients who have ventriculoatrial shunts), and essential mixed cryoglobulinemia.
Treatment of ASPGN is typically supportive and aims to reverse the sodium and fluid retention through the use of diuretics accompanied by restriction of sodium and fluid. Vasodilators also may be used for patients who have severe hypertension. Antibiotics can reduce the risk of transmission of the nephritogenic strain of streptococci to close contacts.
The key follow-up test is a repeat measurement of C3, which usually normalizes within 8 weeks. Patients in whom depression of C3 persists after 12 weeks may require a renal biopsy to rule out MPGN. The prognosis of ASPGN is excellent. Gross hematuria and hypertension usually resolve within a few weeks and proteinuria within a few months. Microscopic hematuria may persist for 1 to 3 years.
A normal urinalysis result is inconsistent with any form of glomerulonephritis, and would, therefore, be highly unlikely in a child who has hypertension and cola-colored urine. A positive urine culture would be unexpected in this clinical scenario. Patients who have hemorrhagic cystitis typically have bright red blood in the urine, often accompanied by clots. Other pertinent parts to the history that are absent in this scenario would be symptoms of dysuria, abdominal pain, frequency, urgency, and possibly fever.
Small vessel vasculitides such as Wegener granulomatosis, microscopic polyangiitis, and Churg Strauss disease are less common causes of glomerulonephritis and, therefore, anti-neutrophil cytoplasmic antibody testing is unlikely to be revealing. Another, less likely diagnostic possibility for the child in the vignette is lupus nephritis. However, anti-nuclear antibody should be measured in the setting of acute nephritis to exclude this possibility.
Question 64
A 1-year-old year boy who has chronic kidney disease from posterior urethral valves presents to your office because his breathing has been noisy for the past 2 hours. His usual medications include calcium carbonate and vitamin D. On physical examination, you note inspiratory stridor. He has not had upper respiratory tract symptoms or fever, and there is no history of choking. The mother reports that the boy was seen by the nephrologist 1 week ago, and because of worsening renal function, he was begun on sodium bicarbonate.
Of the following, the electrolyte abnormality that BEST explains his current symptoms is
answer C
Serum calcium and 1,25 dihydroxyvitamin D concentrations are decreased in children who have chronic kidney disease because of phosphate retention and impaired hydroxylation of 25-hydroxyvitamin D. Physiologic serum calcium concentrations are maintained largely through the use of vitamin D supplements and phosphate binders. As renal function worsens, hypocalcemia can result if vitamin D deficiency or hyperphosphatemia is not addressed or if the use of bicarbonate therapy to treat metabolic acidosis leads to metabolic alkalemia. Metabolic alkalemia increases the binding of calcium to albumin, which decreases the ionized calcium concentration. Decreased ionized calcium can lead to perioral or extremity paresthesias, carpopedal spasm, laryngospasm, and seizures. Children who have hypocalcemia from any cause may be diagnosed mistakenly with croup if they present with tetany-related laryngospasm.
Hyperkalemia may lead to muscle weakness and paresthesias and abnormalities in cardiac conduction. Clinical manifestations usually are preceded by conduction abnormalities, which may result in ventricular fibrillation and asystole. Hypermagnesemia generally is not associated with clinical symptoms. Severe hypophosphatemia can cause proximal muscle weakness, cardiac dysfunction, ataxia, seizures, and coma. Hyponatremia is a cause of nausea, vomiting, hypothermia, lethargy, agitation, headache, and seizures.
Question 233
A 4-year-old female presents with fever, chills, and vomiting. She has had abdominal pain and dysuria for 3 days. Her temperature is 104.2°F (40.1°C), and she has left-sided costovertebral angle tenderness. Laboratory evaluation reveals a white blood cell count of 18.7x103/mcL (18.7x109/L) with 85% neutrophils, 5% bands, 7% lymphocytes, and 3% monocytes. On urinalysis, the urine specific gravity is 1.025 and pH is 6.5, and there is 2+ blood, 1+ protein, 3+ leukocyte esterase, and positive nitrite. Urine microscopy demonstrates 5 to 10 red blood cells/high-power field, 50 to 100 white blood cells/high-power field, and 3+ bacteria. Findings on renal/bladder ultrasonography are normal. After a 3-day hospitalization for administration of intravenous antibiotics, discharge with a prescription for oral antibiotics is planned.
Of the following, the MOST appropriate study to complete this child's evaluation is
answer E
The fever, chills, vomiting, abdominal pain, dysuria, and costovertebral angle tenderness described for the girl in the vignette suggest acute pyelonephritis. Laboratory evaluation demonstrates leukocytosis and abnormal urinalysis findings of hematuria, proteinuria, positive leukocyte esterase, positive nitrite, pyuria, and bacteriuria.
The initial imaging technique in children who have urinary tract infections (UTIs) is renal/bladder ultrasonography to identify anatomic abnormalities, such as hydronephrosis, renal cysts, nephrolithiasis, urolithiasis, ureteral dilatation, duplex collecting system, bladder wall thickening, and ureteroceles.
Following renal/bladder ultrasonography, a child who has a first febrile UTI should undergo voiding cystourethrography (VCUG) to screen for the presence of vesicoureteral reflux (VUR), which typically is present in approximately 30% of patients who experience their first UTI. There are two forms of cystography: fluoroscopic VCUG and radionuclide cystography (RNC). The fluoroscopic VCUG provides more detailed assessment of the reflux severity and reveals much more anatomic detail of the bladder and urethra. Therefore, males who have a first-time UTI must undergo fluoroscopic VCUG initially to rule out posterior urethral valves. Females for whom there are concerns of possible dysfunctional voiding also should undergo a fluoroscopic VCUG to assess bladder capacity and bladder emptying. Other patients and those previously found to have normal bladder and urethral anatomy by fluoroscopic VCUG may be evaluated by RNC, which is associated with reduced radiation exposure.
Abdominal computed tomography has a limited role in evaluating patients who have acute pyelonephritis. It is most useful when the child is not improving despite appropriate antibiotic treatment and concern exists for a renal abscess.
Cystoscopy (useful for stone removal or incisional treatment of a ureterocele). Mercaptoacetyltriglycine (MAG-3)-Tc99 nuclear medicine renal imaging with furosemide (which may detect ureteropelvic junction obstruction), and intravenous pyelography have no role in the evaluation of a child who has a history of acute pyelonephritis. Another nuclear medicine scan, dimercaptosuccinic acid (DMSA)-Tc99, can identify regions of hypoperfusion within the renal parenchyma that occur in acute pyelonephritis or as a result of chronic renal scarring. However, its use generally is limited to those patients in whom uncertainty about the diagnosis of acute pyelonephritis exists.
Question 209
You are evaluating a 5-year-old girl who has a urinary tract infection. She has had four lower urinary tract infections in the last 2 years, all of which resolved completely with oral antibiotics. She denies symptoms of urgency and frequency. The only significant finding on her medical history is constipation. Results of renal ultrasonography and voiding cystourethrography are normal. Her growth parameters and physical examination findings are normal. You prescribe oral trimethoprim-sulfamethoxazole.
Of the following, the MOST appropriate additional step to help reduce the incidence of further urinary tract infection is to
answer C
Constipation is defined by infrequent or difficult passage of large or hard fecal material. It occurs commonly in the pediatric population, and its association with urinary tract dysfunction has been well described. Constipation can cause detrusor instability, which can lead to urinary incontinence, large bladder capacity, and dyscoordinated voiding. Urinary retention is common, either from dyscoordinated voiding or from outflow tract obstruction caused by large rectal fecal masses. All of these types of urinary dysfunction can lead to recurrent urinary tract infections. One study of children who had urinary retention found that 13% had functional constipation as the cause of their retention. Another found that approximately 30% of chronically constipated children complained of urinary incontinence, and 11% had urinary tract infection. Treatment of the underlying constipation improved urinary incontinence and prevented recurrent urinary tract infections.
The girl described in the vignette is otherwise healthy and growing well, and she has no anatomic urinary tract abnormalities. Accordingly, treatment of her underlying constipation is the next best step in the prevention of recurrent infections. Fecal disimpaction, stool softeners, and regular bowel evacuation using timed toilet sitting are the mainstays of treatment.
An evaluation for immunodeficiency is not warranted at this time, but could be considered if her growth parameters were abnormal or if she had additional infections outside of the urinary tract. Renal scintigraphy is used to assess renal anatomy and function and may be warranted in a child who has recurrent urinary tract infections, but it is not helpful in preventing future infections. Anticholinergic therapy, such as oxybutynin, can be helpful if overactive or unstable bladder is suspected, but the girl in the vignette has no symptoms of these conditions. Referral to a pediatric nephrologist may be indicated if evidence of renal dysfunction is present, but treatment of underlying risk factors, such as constipation, should be initiated first.
Question 211
You are evaluating a 12-year-old boy as part of his annual health supervision visit. He has been in good health. His heart rate is 75 beats/min and blood pressure is 132/82 mm Hg using the appropriate-sized cuff. His weight is above the 95th percentile, and his height is at the 50th percentile. He has strong pulses at the right brachial and right femoral regions.
Of the following, the MOST appropriate diagnostic evaluation to pursue at this time is
answer A
Hypertension is a major cause of morbidity and mortality in adults, and growing data suggest that it is becoming a greater clinical problem in the pediatric population, particularly adolescents. Although yet to be defined clearly, the lifelong risks for the child who has hypertension or a prehypertensive state are likely to be substantial. Blood pressure is affected by height, weight, sex, and race. A complete medical history, particularly family history and medications (including over-the-counter supplements), and a thorough physical examination are essential to early and accurate diagnosis of hypertension and assessment of secondary causes, comorbidities, and potential complications.
Specific questions in the history should seek to identify clinical findings that might suggest an underlying systemic disorder, including the presence of gross hematuria, swelling or edema, shortness of breath, or rashes. The past medical history should focus on prior hospitalizations, previous trauma, and urinary tract infections. The family history should evaluate for hypertension, diabetes, obesity, stroke, and renal disease. In addition, the history should explore the possibility of medications or drugs (prescribed, illicit, or over-the-counter) that can be associated with hypertension. An example of the latter may be the use of pseudoephedrine as a nasal decongestant. Additionally, some families and adolescents use dietary supplements, vitamins, herbal remedies, and homeopathic preparations. Some of these "supplements" may be associated with sympathomimetic or hypertensive effects.
The laboratory and diagnostic evaluation of the child who has hypertension should be guided by findings on the history and physical examination. For the pediatric patient who has confirmed hypertension, a screening panel of electrolytes, blood urea nitrogen, and creatinine as well as urinalysis and culture are indicated. Such blood tests are obtained to rule out renal disease.
A urinary drug screen is indicated if the history or patient behavior suggests a possible contribution by illicit substances, drugs, or supplements that can be associated with hypertension. The child described in the vignette is overweight, but he has no historical or physical examination findings suggestive of the use of illicit substances, drugs, or supplements. Echocardiography also is not necessary at this stage of diagnosis because there is no evidence of congenital heart disease such as coarctation or end-organ involvement. Pediatric patients who have comorbid factors such as diabetes or systemic lupus erythematosus should undergo echocardiography as part of their hypertension evaluations. Radionuclide imaging of the kidneys involves exposure to ionizing radiation and typically is reserved for children of this age whose blood pressures are more than 5 mm Hg greater than the 99th percentile. Although renal vascular ultrasonography does not involve ionizing radiation, it also generally is reserved for young children whose blood pressures are beyond the 95th percentile and older children and adolescents whose blood pressures exceed the 99th percentile.
Question 237
A 12-year-old African-American girl presents to your office with a 2-day history of gross hematuria. She describes the urine as brown. She states that she has had an upper respiratory tract infection for about 3 days. She denies dysuria, urgency, or frequency. Her vital signs and physical examination findings are normal. Urinalysis reveals: specific gravity, 1.025; pH, 6.5; large blood; no protein; too numerous-to-count red blood cells; and 0 to 2 white blood cells. Serum electrolyte concentrations are normal.
Of the following, the MOST likely cause of her gross hematuria is
answer B
Immunoglobulin A nephropathy (IgAN) or Berger disease is the most common cause of primary glomerulonephritis in adults in the world. In contrast, only about 5% to 10% of children who have glomerular disease exhibit IgAN. Although once considered to be a random disease with no genetic component, the prevailing opinion now is that there may be a strong familial component to IgAN.
The pathogenesis of IgAN remains elusive. It is not a classically defined autoimmune disease, although the disease develops from deposition of IgA-containing immune complexes in the kidney. It is tempting to assume that the pathogenesis is related to mucosal IgA because the disease often follows an upper respiratory tract infection, but deposited IgA is predominantly polymeric IgA1. The association of some cases of IgAN with syndromes that affect the respiratory or gastrointestinal (GI) tracts supports the relationship between IgAN and the immune system. Moreover, it has been shown that the gross hematuria worsens during or after upper respiratory tract or GI infections. Serum IgA concentrations may be elevated in about 50% of patients who have IgAN, making this finding relatively nonspecific and not diagnostic. The natural history of the disease varies. About one third of patients have a benign course, one third experience slow progression to renal failure, and one third have a more progressive course in which renal failure develops within 20 years. IgAN is more common in whites and Asians than other ethnic groups and is observed frequently in American Indians. IgAN is more common in males than females.
The girl in the vignette has the classic presentation of IgAN: a brief history of painless, gross hematuria following an upper respiratory tract infection. Her urinalysis demonstrates too numerous-to-count red blood cells but no protein, and her renal function is normal. Children who have focal segmental glomerulosclerosis may develop gross hematuria, but this is not common. Patients who have lupus nephritis may develop either microscopic or gross hematuria, but they often have associated symptoms (eg, rashes, arthritis, anorexia). Children who have membranoproliferative glomerulonephritis may develop gross hematuria, but they often present with proteinuria, edema, and hypertension. Finally, children who have papillary necrosis usually have sickle cell disease or trait, and the gross hematuria generally is associated with pain, typically abdominal or flank pain.
The follow-up of a patient who has IgAN includes at least quarterly assessment of urine protein by urinalysis and determination of a random protein-to-creatinine ratio (P/C). A rising urine P/C is highly predictive of progressive renal disease. Frequent measurement of serum electrolyte values is vital, especially for patients who have evidence of significant proteinuria or hypertension. Treatment typically begins with agents to reduce proteinuria: angiotensin-converting enzyme inhibitors or angiotensin receptor blockers. Oral corticosteroids may be effective in some cases but generally do not alter the final outcome significantly. Use of calcineurin inhibitors such as cyclosporine or mycophenolate mofetil has been shown to slow the progression of IgAN in adults, but larger trials are necessary to determine their efficacy fully.
Question 174 2006
A 7 year old girl presents with a rash on the lower extremities that extends to the buttocks. She also reports swollen and aching knees and ankles and intermittent abdominal pain. Her vital signs are normal, and the physical examination reveals swollen and tender joints and abdominal tenderness. She has multiple purpura on her lower extremities. Her complete blood count and serum electrolyte concentrations are normal, but urinalysis reveals moderate blood and 3+protein.
Based on her urinalysis results, the BEST course of action is to
answer B
HSP is the most common vasculitis in children. It is characterized by a purpuric and sometimes petechial rash of the lower extremities, arthritis, and abdominal pain. Some patients have all of these features, some may have only 1 or 2. About 35-50% of patients have renal involvement. This generally is manifested by isolated hematuria, but some patients may have more severe involvement, with proteinuria, elevated BP, reduced GFR. The presence of nephrotic syndrome, increased BP, proteinuria, and reduced GFR generally predicts more severe and long-standing renal disease.
HSP is a vasculitis of unknown cause that affects virtually all blood vessels throughout the body. Some patients only have one episode, but many have recurrences. Oddly, the recurrences may present with different symptoms than the original episode. For most patients, the extent of renal involvement during the 1st presentation predicts future renal involvement. However, in a small number of patients, a benign early course (with no or minimal renal disease) may be followed by more extensive renal impairment.
Pathologically, HSP nephritis may reveal deposits of immunoglobulin A in the mesangial cells of the kidney. The appearance of IgA depositis in HSP nephritis is similar to that seen in patients who have IgA nephropathy. However, patients who have HSP nephritis may have extensive inflammation and scarring (called crescents) in some glomeruli. In the small number of patients who have HSP nephritis with crescents, renal function may deteriorate rapidly. Because severe HSP nephritis generally is unresponsive to steroid therapy, treatment of severe crescentric HSP nephritis may require either IV cyclophosphamide or even plasmapheresis if the renal deterioration does not abate. The outcome is guarded if there is severe renal impairment. For patients who have milder HSP nephritis and nephrotic syndrome, a combination of oral steroids and azathioprine has proven beneficial in several studies.
The best method to assess changes in urine protein quantity for patients who have nephrotic syndrome is to obtain intermittent random protein and creatinine measurements or the PC ratio. A renal biopsy may be indicated if the renal diagnosis is in doubt or later in HSP to stage nephritis but this is not mandatory at presentation because some children may have spontaneous remissions in the first 6 months of presentation with HSP and nephrotic syndrome. Renal U/S will not help in the evaluation and management of this patient.
Question 254 2006
A 3 month old boy recently was recently treated for a UTI. Renal U/S reveals mild L hydronephrosis, and VCUG reveals L grade IV vesicoureteral reflux. After completion of the current course of antibiotics for the UTI, the MOST appropriate course of management for this infant is
answer A
UTI are common in children. Although most infants and children who develop UTIs do not have an underlying urinary tract malformation, it is imperative to evaluate infants and young children to determine if a malformation is present after the first UTI. Controversy surrounds the age at which it is essential to perform an evaluation after a first UTI. Because the urethra is shorter in females, it is easier for females to develop a UTI without any associated anomaly. Thus, most guidelines recommend performing renal U/S to assess general architecture of the kidneys after a first UTI is any child younger than 5 years if age. Hydronephrosis, renal scars, or abnormal renal size may herald an underlying renal malformation.
Significant controversy and differences in practice exist with two other issues. 1) At what age is a VCUG required? 2) If VUR or bladder/voiding dysfunction is identified, is antibiotic prophylaxis required?
Within the diverse opinions are some general agreements.Any child 3 years of age or younger who has documented first UTI should undergo a VCUG, preferably about 1 week after the UTI is detected and treatment initiated. A repeat negative urine culture is required prior to performing a VCUG. Antibiotic prophylaxis generally is not recommended for any patient who has absent or grade 1 VUR. For grades II-V VUR or recurrent UTIs in patients who have voiding dysfunction, most clinicians recommend antibiotic prophylaxis. If the VUR or the voiding symptoms resolve, the antibiotic prophylaxis may be discontinued.
Deflux surgery is a technique in which artificial substance is injected into the region of insertion of the ureter into the bladder, preventing reflux of material into the ureter. This technique is indicated for grade III or higher VUR that doesn’t remit spontaneously after t least one year of observation. It is too early in this child’s history to recommend this procedure. Because the child has grade IV VUR, withholding antibiotic prophylaxis is absolutely contraindicated at this time. Probiotics have been shown to be effective in patients who have chronic UTIs but their efficacy has not been tested in high grade VUR. Finally, similar to deflux surgery, surgical reimplantation may be indicated if there is no resolution of high grade reflux 1 year later, but it is too early to make that determination in this child.