Medical School · Year 3 · Pediatrics · includes a quiz and discussion video

Seminar 11: Pediatric Renal Disorders

Unit 3: Pediatrics Clerkship

Learning Objectives

1. Interpret urinalysis findings and apply appropriate collection methods for pediatric patients of varying ages
2. Differentiate between glomerular and non-glomerular causes of hematuria and develop an evaluation algorithm
3. Evaluate proteinuria using quantitative methods and distinguish pathologic from benign causes
4. Diagnose and manage nephrotic syndrome with emphasis on minimal change disease and steroid therapy
5. Recognize post-streptococcal glomerulonephritis and other forms of glomerulonephritis including IgA nephropathy
6. Identify congenital kidney anomalies, acute and chronic kidney disease, and enuresis with appropriate management strategies

Lecture Outline

Section 1: Urinalysis Interpretation

Urinalysis serves as a fundamental diagnostic tool in pediatric nephrology, providing crucial information about the health of the urinary tract and kidneys. The interpretation of urinalysis findings requires a systematic approach that begins with proper specimen collection and extends through careful analysis of both chemical and microscopic components. In pediatric practice, the quality of the urine specimen depends significantly on the collection method employed, which must be tailored to the child's age, developmental status, and the urgency of the clinical situation. Understanding the nuances of urinalysis interpretation allows clinicians to rapidly identify conditions ranging from simple urinary tract infections to complex glomerular diseases.

The collection method for obtaining a urine specimen varies considerably based on the child's toilet training status and the clinical need for diagnostic accuracy. For toilet-trained children, a clean catch midstream specimen provides reliable results and should be the standard approach. When dealing with non-toilet-trained infants and young children, catheterized specimens offer the most accurate results when the diagnosis is critical, though bag specimens may suffice for screening purposes despite their high contamination rates. Suprapubic aspiration remains the gold standard for neonates and young infants when urinary tract infection must be definitively diagnosed, as this method bypasses the contaminated perineal area entirely.

Normal urinalysis parameters provide the baseline against which abnormal findings are assessed. The urine pH typically ranges from 4.5 to 8, reflecting the kidney's role in acid-base homeostasis, while specific gravity between 1.005 and 1.030 indicates the kidney's concentrating ability. Protein should be negative to trace on dipstick testing in healthy children, and blood should be entirely absent. Microscopic examination should reveal fewer than five white blood cells and fewer than five red blood cells per high-power field, with no bacteria visible. Deviations from these parameters warrant further investigation tailored to the specific abnormality detected.

Dipstick analysis provides rapid semiquantitative assessment of several important urinary constituents. Leukocyte esterase positivity suggests pyuria and possible urinary tract infection, while nitrite detection indicates the presence of gram-negative bacteria capable of reducing urinary nitrates. Proteinuria on dipstick requires confirmation and quantification, and may indicate glomerular or tubular pathology depending on the clinical context. The presence of blood on dipstick testing demands microscopic confirmation, as certain substances can cause false-positive results. Glucose detection may indicate diabetes mellitus or tubular dysfunction, each requiring distinct diagnostic approaches. Microscopic examination adds critical diagnostic information, with red blood cell casts pathognomonic for glomerulonephritis, white blood cell casts suggesting pyelonephritis or interstitial nephritis, dysmorphic red blood cells indicating glomerular origin bleeding, and various crystal formations suggesting stone disease or metabolic abnormalities.

<image>Panel A: Demonstration of proper clean catch urine collection technique in a toilet-trained child with step-by-step hand hygiene and midstream collection. Panel B: Cross-sectional anatomical diagram showing suprapubic aspiration needle placement in a neonate with bladder filled above pubic symphysis. Panel C: Magnified microscopy view showing comparison of isomorphic red blood cells versus dysmorphic acanthocytes characteristic of glomerular bleeding. Panel D: Color-coded dipstick reagent pad interpretation chart showing gradations from negative to strongly positive for protein, blood, leukocyte esterase, and nitrites.</image>

Section 2: Hematuria

Hematuria in children presents a diagnostic challenge that requires systematic evaluation to distinguish benign causes from serious underlying pathology. The presence of blood in the urine may be discovered incidentally on routine dipstick testing or may present dramatically as grossly discolored urine, prompting parental concern and urgent medical evaluation. Proper definition requires microscopic confirmation showing greater than five red blood cells per high-power field on at least two separate specimens, as single positive dipstick results may not indicate true hematuria. The clinical approach differs substantially depending on whether the hematuria is microscopic and asymptomatic or gross and accompanied by additional symptoms.

Distinguishing between glomerular and non-glomerular sources of hematuria provides the essential framework for diagnostic evaluation. Glomerular hematuria typically produces brown or tea-colored urine due to hemoglobin degradation during transit through the nephron, while non-glomerular bleeding usually appears bright red or pink. The presence of red blood cell casts on microscopy virtually confirms glomerular origin, as these fragile structures can only form within the tubular lumen where Tamm-Horsfall protein provides the matrix. Dysmorphic red blood cells with irregular membranes and protrusions result from passage through the damaged glomerular basement membrane, while isomorphic cells retain their normal biconcave shape, suggesting lower urinary tract origin. Concurrent proteinuria strongly suggests glomerular disease, as the damaged filtration barrier allows both protein and blood to pass.

The differential diagnosis of hematuria spans multiple organ systems and pathophysiologic mechanisms. Glomerular causes include IgA nephropathy, the most common glomerulonephritis in older children and adolescents, as well as post-streptococcal glomerulonephritis and hereditary conditions such as Alport syndrome. Non-glomerular causes encompass urinary tract infections, which represent the most common cause of hematuria in children, along with hypercalciuria, urolithiasis, and traumatic injury to the urinary tract. Transient benign hematuria may follow vigorous exercise or occur with fever, while menstrual contamination must be considered in adolescent females. Rare but serious causes including malignancy and coagulopathy require consideration when clinical features are atypical.

The evaluation of hematuria proceeds in stepwise fashion based on clinical presentation and initial findings. Confirmation of hematuria requires repeat urinalysis, as transient causes are common and single abnormal results may not warrant extensive workup. A thorough history should explore recent infections, trauma, family history of kidney disease, and medication use. Physical examination focuses on blood pressure measurement, assessment for edema, and abdominal palpation. Laboratory evaluation typically includes serum creatinine to assess kidney function and complement levels to evaluate for glomerulonephritis, with urinary calcium-to-creatinine ratio screening for hypercalciuria. Referral to pediatric nephrology is indicated for persistent hematuria lasting more than several months, any episode of gross hematuria, hematuria with significant proteinuria, or findings suggestive of glomerulonephritis.

<image>Panel A: Flowchart algorithm for evaluation of pediatric hematuria starting with dipstick positive and branching based on microscopy confirmation, presence of casts, and proteinuria status. Panel B: Side-by-side comparison of urine specimens showing clear normal urine, pink non-glomerular hematuria, and dark tea-colored glomerular hematuria. Panel C: High-power microscopy field demonstrating a red blood cell cast surrounded by dysmorphic acanthocytes in glomerulonephritis. Panel D: Anatomical diagram of the urinary tract with color-coded regions indicating likely bleeding sources based on clinical characteristics.</image>

Section 3: Proteinuria

Proteinuria in children requires careful assessment to determine whether the finding represents benign variation or significant renal pathology. The detection of protein in urine may occur incidentally during routine screening or targeted evaluation, and the clinical significance varies enormously based on quantity, persistence, and associated findings. Most healthy children excrete small amounts of protein that remain below the detection threshold of standard dipstick testing, making any positive result worthy of further characterization. The challenge lies in efficiently distinguishing the many children with transient or orthostatic proteinuria from those with early glomerular disease requiring intervention.

Several methods exist for assessing proteinuria, each with particular strengths and limitations in pediatric practice. Dipstick testing provides rapid semiquantitative results but is affected by urine concentration, potentially missing dilute specimens with significant protein or overcalling concentrated specimens with normal protein excretion. The random urine protein-to-creatinine ratio corrects for concentration and serves as an excellent screening tool, with values below 0.2 considered normal in children older than two years. Twenty-four-hour urine collection remains the gold standard for precise quantification but presents practical challenges in children, particularly those not yet toilet trained. Nephrotic-range proteinuria is defined as greater than 40 mg per square meter per hour or a protein-to-creatinine ratio exceeding 2.

Proteinuria may be classified by pattern and cause, with important implications for evaluation and prognosis. Transient proteinuria occurs with fever, exercise, dehydration, and stress, resolving spontaneously once the precipitating factor abates. Orthostatic proteinuria, a benign condition common in adolescents, produces elevated protein excretion only when upright, with normal first-morning specimens after overnight recumbency. Persistent proteinuria requires thorough evaluation regardless of quantity. Glomerular proteinuria involves loss of high-molecular-weight proteins like albumin through a damaged filtration barrier, while tubular proteinuria reflects impaired reabsorption of normally filtered low-molecular-weight proteins, suggesting different underlying disease processes.

The evaluation of proteinuria follows a logical sequence designed to efficiently identify pathology while avoiding unnecessary testing for benign conditions. The first step involves obtaining a first-morning urine specimen, as a negative result in this concentrated sample effectively rules out orthostatic proteinuria and provides reassurance in many cases. Quantification using the protein-to-creatinine ratio establishes the severity of protein loss and guides further workup. Persistent proteinuria warrants measurement of serum blood urea nitrogen, creatinine, albumin, and complement levels to assess kidney function and screen for nephrotic syndrome or glomerulonephritis. Referral to pediatric nephrology is appropriate for persistent proteinuria exceeding normal range, nephrotic-range proteinuria, or proteinuria accompanied by hematuria, hypertension, or reduced kidney function.

<image>Panel A: Diagram illustrating the glomerular filtration barrier with podocytes, basement membrane, and endothelium, showing normal protein retention versus albumin leakage in disease. Panel B: Graph plotting protein-to-creatinine ratios throughout the day in orthostatic proteinuria, demonstrating normal morning values rising after ambulation. Panel C: Step-by-step evaluation protocol flowchart for pediatric proteinuria beginning with first morning specimen and progressing through quantification and referral decisions. Panel D: Comparison images of normal versus edematous child with nephrotic syndrome showing periorbital puffiness and dependent edema.</image>

Section 4: Nephrotic Syndrome

Nephrotic syndrome represents one of the most important kidney disorders in pediatric nephrology, characterized by the tetrad of massive proteinuria, hypoalbuminemia, generalized edema, and hyperlipidemia. This clinical syndrome results from increased glomerular permeability allowing large quantities of plasma proteins, particularly albumin, to escape into the urine. The annual incidence in children is approximately 2 to 7 per 100,000, with a peak age of onset between 2 and 6 years. Understanding the pathophysiology, classification, and management of nephrotic syndrome is essential for pediatric practitioners, as prompt recognition and appropriate treatment significantly impact outcomes.

The defining criteria for nephrotic syndrome establish thresholds that distinguish this condition from isolated proteinuria. Nephrotic-range proteinuria exceeds 40 mg per square meter per hour on timed collection or produces a urine protein-to-creatinine ratio greater than 2 on spot testing. Serum albumin falls below 2.5 g/dL as urinary losses exceed hepatic synthetic capacity. Edema develops as oncotic pressure drops, initially appearing in dependent areas and around the eyes before progressing to generalized anasarca with ascites and pleural effusions. Hyperlipidemia develops as the liver upregulates lipoprotein synthesis in response to low oncotic pressure, producing elevated cholesterol and triglycerides that may reach striking levels.

Several distinct pathologic entities can produce the nephrotic syndrome, with minimal change disease accounting for approximately 80% of cases in children. Minimal change disease derives its name from the normal appearance of glomeruli on light microscopy, with only electron microscopy revealing the characteristic diffuse podocyte foot process effacement. Focal segmental glomerulosclerosis involves scarring affecting portions of some glomeruli and may be steroid-resistant, carrying a less favorable prognosis. Membranous nephropathy occurs less commonly in children than adults but should be considered in adolescents. Secondary causes of nephrotic syndrome include systemic lupus erythematosus, infections such as hepatitis B and HIV, and medication effects, requiring directed evaluation when clinical features suggest non-primary disease.

The clinical features of nephrotic syndrome extend beyond the defining laboratory abnormalities to include important complications requiring monitoring and management. Edema typically begins periorbitally, most noticeable upon awakening, then progresses to involve the scrotum or labia, lower extremities, and eventually the trunk with accumulation of ascitic and pleural fluid. Weight gain reflects fluid retention and helps monitor disease activity. Children with nephrotic syndrome face increased infection risk, particularly from encapsulated organisms like Streptococcus pneumoniae, due to urinary immunoglobulin losses. Hypercoagulability results from urinary loss of anticoagulant proteins alongside hepatic overproduction of clotting factors, creating thrombotic risk that may manifest as deep vein thrombosis, pulmonary embolism, or renal vein thrombosis. These complications require vigilant monitoring throughout disease episodes.

<image>Panel A: Child with nephrotic syndrome demonstrating characteristic periorbital edema, abdominal distension from ascites, and scrotal swelling. Panel B: Electron microscopy image showing diffuse podocyte foot process effacement characteristic of minimal change disease with annotated normal podocyte for comparison. Panel C: Graph showing the relationship between serum albumin levels and edema formation with threshold delineation. Panel D: Diagram illustrating the pathophysiology of nephrotic syndrome from glomerular permeability defect through protein loss to clinical manifestations.</image>

Section 5: Nephrotic Syndrome Management

The management of nephrotic syndrome in children centers on corticosteroid therapy, which produces remission in the vast majority of patients with minimal change disease while simultaneously revealing those with steroid-resistant pathology requiring different approaches. Initial treatment typically employs prednisone at 2 mg/kg/day with a maximum dose of 60 mg, administered for six weeks of daily therapy followed by gradual tapering over several additional weeks. Response to steroids carries prognostic significance, with approximately 95% of children with minimal change disease achieving remission within four weeks of treatment initiation. The patterns of steroid response define subsequent management strategies and help predict long-term outcomes.

The terminology describing steroid response provides a framework for classifying disease behavior and guiding treatment decisions. Steroid-sensitive nephrotic syndrome denotes achievement of complete remission, defined as resolution of proteinuria to trace or negative on dipstick for three consecutive days, within four weeks of adequate corticosteroid therapy. Steroid-resistant disease indicates failure to achieve remission despite eight weeks of treatment and warrants kidney biopsy and alternative immunosuppressive therapy. Relapse refers to return of nephrotic-range proteinuria after documented remission and occurs commonly, with many children experiencing multiple relapses over years. Frequently relapsing disease involves two or more relapses within six months or four or more within any twelve-month period. Steroid-dependent disease describes relapse occurring during steroid taper or within two weeks of discontinuation, indicating inability to maintain remission off therapy.

Treatment of relapsing nephrotic syndrome aims to minimize cumulative steroid exposure while maintaining disease control. Infrequent relapses can be managed with repeated standard corticosteroid courses similar to initial therapy. Frequently relapsing or steroid-dependent disease requires steroid-sparing agents to prevent the significant morbidity associated with prolonged corticosteroid use. Cyclophosphamide, typically given as a twelve-week oral course, can induce prolonged remission in many patients. Calcineurin inhibitors including cyclosporine and tacrolimus effectively maintain remission but require ongoing administration with monitoring for nephrotoxicity. Mycophenolate mofetil offers another steroid-sparing option with a favorable side effect profile. Rituximab has emerged as a valuable therapy for difficult cases unresponsive to conventional agents.

Complications of nephrotic syndrome require proactive management alongside immunosuppressive therapy. Infection prevention includes ensuring pneumococcal vaccination and maintaining heightened vigilance for early signs of bacterial illness, with low threshold for empiric antibiotic coverage. Thrombosis prevention involves encouraging mobilization, adequate hydration, and considering prophylactic anticoagulation in high-risk situations such as severe hypoalbuminemia or prolonged hospitalization. Steroid side effects including growth suppression, bone demineralization, metabolic disturbances, and behavioral changes accumulate with repeated courses, reinforcing the importance of steroid-sparing strategies. Hypovolemia may develop despite apparent fluid overload, manifesting as tachycardia, abdominal pain, and poor peripheral perfusion; careful albumin infusion followed by diuretics may be required in such cases. The prognosis for childhood nephrotic syndrome is generally favorable, with most children with minimal change disease eventually outgrowing their tendency to relapse, though focal segmental glomerulosclerosis carries risk of progression to end-stage renal disease.

<image>Panel A: Timeline diagram showing standard corticosteroid treatment protocol for initial episode with daily prednisone followed by alternate-day taper. Panel B: Flowchart depicting classification of nephrotic syndrome based on steroid response with corresponding treatment pathways. Panel C: Graph showing cumulative steroid exposure over multiple relapses with threshold line indicating toxicity risk zone. Panel D: Side-by-side comparison of child at disease presentation with edema versus same child in remission after treatment.</image>

Section 6: Glomerulonephritis

Glomerulonephritis encompasses a group of disorders characterized by inflammation of the glomeruli, manifesting clinically with hematuria, variable proteinuria, hypertension, and impaired kidney function. Post-streptococcal glomerulonephritis represents the prototypical and most common form in children, serving as an important model for understanding immune-complex-mediated glomerular injury. This condition follows infection with nephritogenic strains of group A streptococcus, whether pharyngitis or skin infection, with a characteristic latent period between infection and renal manifestations. Recognition of post-streptococcal glomerulonephritis and differentiation from other forms of glomerulonephritis guides appropriate management and prognostication.

Post-streptococcal glomerulonephritis develops one to two weeks after streptococcal pharyngitis or three to six weeks after streptococcal skin infection, with peak incidence between ages 5 and 12 years. The classic presentation includes sudden onset of gross hematuria producing dark tea-colored or cola-colored urine, periorbital and peripheral edema from sodium and fluid retention, and hypertension that may be severe enough to cause symptoms. Laboratory findings reveal depressed serum C3 complement levels reflecting consumption by immune complexes, while C4 typically remains normal, indicating activation of the alternative complement pathway. Elevated anti-streptolysin O titer confirms recent pharyngeal infection, while anti-DNase B better detects preceding skin infection. Urinalysis shows hematuria with red blood cell casts and variable proteinuria typically less than nephrotic range.

Treatment of post-streptococcal glomerulonephritis is primarily supportive, as the condition is self-limited in the vast majority of cases. Sodium and fluid restriction help control edema and hypertension during the acute phase. Antihypertensive therapy should be administered when blood pressure exceeds safe thresholds, with loop diuretics often providing dual benefit for blood pressure and volume control. Dialysis is rarely required but may be necessary for severe oliguria with volume overload or uremia. Antibiotic treatment is indicated if active streptococcal infection persists but does not alter the course of established glomerulonephritis. The prognosis is excellent, with over 95% of children recovering completely; C3 levels normalize within 8 to 12 weeks, and persistent complement depression should prompt reevaluation for alternative diagnoses.

IgA nephropathy represents the most common chronic glomerulonephritis and presents differently from post-streptococcal disease. Gross hematuria characteristically occurs during or within one to two days of upper respiratory infection, contrasting with the one to two week latency of post-streptococcal glomerulonephritis. This timing reflects the distinct pathophysiology involving abnormal IgA deposition in the mesangium rather than post-infectious immune complex formation. Complement levels remain normal in IgA nephropathy, providing another distinguishing feature. The clinical course varies widely, with some patients experiencing rare recurrent episodes without progression while others develop chronic kidney disease over years to decades. Kidney biopsy confirms the diagnosis by demonstrating mesangial IgA deposits on immunofluorescence. Other important glomerulonephritides in children include lupus nephritis associated with systemic lupus erythematosus and characterized by low C3 and C4 with positive serologic markers, membranoproliferative glomerulonephritis with persistently low complement and features of both nephritic and nephrotic syndrome, Alport syndrome causing hereditary nephritis with sensorineural hearing loss and ocular abnormalities, and rapidly progressive glomerulonephritis requiring urgent treatment to prevent permanent renal injury.

<image>Panel A: Comparison timeline showing latent period between streptococcal infection and glomerulonephritis for pharyngitis versus skin infection origins. Panel B: Immunofluorescence microscopy images showing granular IgG deposits along capillary walls in post-streptococcal glomerulonephritis versus mesangial IgA deposits in IgA nephropathy. Panel C: Graph showing typical C3 complement depression and recovery over 12 weeks in post-streptococcal glomerulonephritis. Panel D: Clinical photograph of child with acute glomerulonephritis demonstrating periorbital edema, facial puffiness, and tea-colored urine specimen.</image>

Section 7: Congenital Kidney Anomalies

Congenital anomalies of the kidney and urinary tract represent a significant proportion of chronic kidney disease in children and include a spectrum of structural abnormalities affecting kidney formation, positioning, and the collecting system. Vesicoureteral reflux, the retrograde flow of urine from bladder to ureter and kidney, is among the most common urologic abnormalities diagnosed in children, often discovered during evaluation of urinary tract infection or identified on prenatal ultrasound showing hydronephrosis. Understanding the grading, natural history, and management of reflux allows appropriate counseling and treatment decisions that balance infection prevention against the morbidity of intervention.

Vesicoureteral reflux is graded on a scale of I to V based on the findings of voiding cystourethrogram, with increasing grades reflecting greater severity of reflux and ureteral dilation. Grade I reflux reaches only the ureter without dilation, while grade II involves the renal pelvis without calyceal dilation. Grade III shows mild dilation of the ureter and collecting system, and grade IV demonstrates moderate dilation with blunting of the calyces. Grade V, the most severe form, shows massive dilation with tortuous ureter and significant calyceal blunting. The grade of reflux influences management decisions and predicts the likelihood of spontaneous resolution, with lower grades resolving in the majority of cases while higher grades more often require surgical intervention.

Management of vesicoureteral reflux has evolved considerably, with observation now playing a larger role as evidence has accumulated regarding spontaneous resolution rates and the limited benefit of antibiotic prophylaxis in many patients. Low-grade reflux, encompassing grades I and II, is managed primarily with observation, maintaining vigilance for urinary tract infection, and using continuous antibiotic prophylaxis selectively based on individual risk factors and family preference. Moderate-grade reflux may be managed with observation or surgical correction depending on the presence of breakthrough infections, renal scarring, and parental preferences. High-grade reflux involving grades IV and V more often requires surgical correction, either through open ureteral reimplantation or endoscopic injection of bulking agents at the ureteral orifice. Regardless of grade, the goal of management is preventing renal scarring from infected urine refluxing to the kidney.

Other important congenital urologic anomalies include hydronephrosis and posterior urethral valves. Hydronephrosis, dilation of the renal collecting system, is commonly identified on prenatal ultrasound and may result from ureteropelvic junction obstruction, vesicoureteral reflux, ureterovesical junction obstruction, or posterior urethral valves. Ureteropelvic junction obstruction is the most common cause of significant congenital hydronephrosis and often resolves spontaneously in mild cases, though surgery may be needed for progressive dilation or decreased function. Posterior urethral valves, occurring only in males, represent tissue leaflets obstructing the prostatic urethra and cause bilateral hydronephrosis and bladder distension, often identified prenatally on ultrasound. Voiding cystourethrogram confirms the diagnosis, and treatment involves endoscopic valve ablation. Despite relief of obstruction, boys with posterior urethral valves remain at significant risk for chronic kidney disease due to renal dysplasia and ongoing bladder dysfunction, requiring long-term nephrology follow-up.

<image>Panel A: Graded diagram showing vesicoureteral reflux grades I through V with progressive ureteral dilation and calyceal blunting. Panel B: Voiding cystourethrogram radiograph demonstrating bilateral grade IV reflux with dilated tortuous ureters and blunted calyces. Panel C: Anatomical cross-section comparing normal ureterovesical junction with short intramural tunnel allowing reflux. Panel D: Ultrasound images showing prenatal bilateral hydronephrosis and distended bladder typical of posterior urethral valves.</image>

Section 8: Hypertension

Hypertension in children requires careful evaluation to identify underlying causes, which differ substantially from the predominantly essential hypertension seen in adults. Blood pressure norms in children are defined by percentiles based on age, sex, and height, requiring use of standardized tables for accurate classification. The Fourth Report from the National High Blood Pressure Education Program Working Group provides the classification system used in pediatric practice, recently updated to simplify thresholds for adolescents. Secondary causes predominate in younger children and those with more severe hypertension, while primary hypertension has become increasingly common with the obesity epidemic.

Blood pressure classification in children establishes normal, elevated, and hypertensive categories with distinct management implications. Normal blood pressure falls below the 90th percentile for age, sex, and height. Elevated blood pressure, previously termed prehypertension, includes readings from the 90th percentile up to but not including the 95th percentile. Stage 1 hypertension ranges from the 95th percentile to the 95th percentile plus 12 mmHg. Stage 2 hypertension, indicating more severe elevation, exceeds the 95th percentile by more than 12 mmHg. For adolescents aged 13 and older, simplified thresholds align with adult definitions, with elevated blood pressure being 120-129/<80, stage 1 hypertension 130-139/80-89, and stage 2 hypertension 140/90 or higher.

The etiology of pediatric hypertension varies by age and severity. In infancy, renovascular disease such as renal artery stenosis or thrombosis and coarctation of the aorta are leading causes. Throughout childhood, renal parenchymal disease including glomerulonephritis, reflux nephropathy, and polycystic kidney disease accounts for a substantial proportion of secondary hypertension. In adolescence, primary or essential hypertension becomes more common, particularly in the setting of obesity, though secondary causes still require consideration. Endocrine disorders including pheochromocytoma, hyperthyroidism, and congenital adrenal hyperplasia may present with hypertension at any age. Drug effects from corticosteroids, stimulants, and sympathomimetics should be considered in the appropriate clinical context.

Evaluation of pediatric hypertension aims to identify secondary causes and assess target organ damage. Basic laboratory studies include comprehensive metabolic panel assessing kidney function and electrolytes, urinalysis screening for renal disease, and lipid panel and fasting glucose evaluating metabolic syndrome. Renal ultrasound examines kidney structure and size, while echocardiography assesses for left ventricular hypertrophy indicating chronic pressure overload and screens for coarctation. Further testing is guided by clinical findings and may include plasma renin activity, catecholamines, or imaging of renal vasculature. Treatment begins with lifestyle modifications including weight loss, dietary sodium restriction, and increased physical activity. Pharmacologic therapy is indicated for stage 2 hypertension, stage 1 hypertension not responding to lifestyle measures, hypertension with target organ damage, or hypertension with underlying conditions such as diabetes or chronic kidney disease. First-line medications include ACE inhibitors or angiotensin receptor blockers, particularly in patients with proteinuria or diabetes, as well as calcium channel blockers, thiazide diuretics, and beta-blockers, with selection guided by comorbidities and contraindications. The treatment goal is blood pressure below the 90th percentile or below 130/80 in adolescents.

<image>Panel A: Pediatric blood pressure percentile chart showing zones for normal, elevated, stage 1, and stage 2 hypertension with age on x-axis. Panel B: Pie chart depicting relative frequency of hypertension etiologies in children with renal causes predominating. Panel C: Echocardiogram image demonstrating left ventricular hypertrophy from chronic hypertension with wall thickness measurements. Panel D: Evaluation algorithm flowchart for newly diagnosed pediatric hypertension with decision points for testing and referral.</image>

Section 9: Acute and Chronic Kidney Disease

Acute kidney injury in children encompasses a sudden decline in kidney function with diverse etiologies categorized as prerenal, intrinsic renal, and postrenal. Recognition of acute kidney injury requires awareness that children may maintain adequate urine output despite significant functional impairment, making reliance on creatinine trends essential. The KDIGO criteria adapted for pediatric use define acute kidney injury stages based on creatinine rise from baseline and urine output reduction. Understanding the differential diagnosis and initial management of acute kidney injury allows stabilization and often reversal of this potentially life-threatening condition.

Prerenal acute kidney injury results from decreased renal perfusion without intrinsic kidney damage and represents the most common category in children. Dehydration from vomiting, diarrhea, or inadequate intake reduces effective circulating volume, as does hemorrhage, sepsis with third-spacing, and cardiac dysfunction. Intrinsic renal injury involves direct damage to kidney structures and includes acute tubular necrosis from prolonged ischemia or nephrotoxins, glomerulonephritis, interstitial nephritis from medications or infection, and hemolytic uremic syndrome. Postrenal or obstructive acute kidney injury results from impaired urine flow at any level from calyces to urethra, requiring bilateral obstruction or obstruction of a solitary kidney to significantly impact function. The distinction between prerenal and intrinsic injury may be assessed through fractional excretion of sodium, though interpretation requires caution in young infants and patients receiving diuretics.

Hemolytic uremic syndrome deserves particular attention as an important cause of acute kidney injury in previously healthy children. The classic triad comprises microangiopathic hemolytic anemia with schistocytes on blood smear, thrombocytopenia, and acute kidney injury. The typical form follows diarrheal illness caused by Shiga toxin-producing Escherichia coli, particularly serotype O157:H7, with bloody diarrhea preceding the syndrome by several days. Management is supportive, focusing on careful fluid and electrolyte management and dialysis if needed for uremia, hyperkalemia, or volume overload. Critically, antibiotics should not be given for the diarrheal prodrome, as they may increase toxin release and worsen outcomes. Red blood cell transfusion is often required for symptomatic anemia, while platelet transfusion is generally avoided unless active bleeding occurs. Most children recover kidney function, though some develop chronic kidney disease or hypertension.

Chronic kidney disease in children is staged based on estimated glomerular filtration rate, with implications for monitoring and management that differ across stages. Stage 1 indicates kidney damage with normal or elevated GFR above 90 mL/min/1.73m2, while stage 2 shows mildly decreased GFR between 60-89. Stage 3 encompasses moderate reduction to 30-59, stage 4 severe reduction to 15-29, and stage 5 or kidney failure indicates GFR below 15, at which point renal replacement therapy becomes necessary. Management of chronic kidney disease aims to slow progression through control of blood pressure and proteinuria, typically with ACE inhibitors or angiotensin receptor blockers. Complications requiring management include anemia treated with erythropoietin-stimulating agents and iron supplementation, and metabolite bone disease managed with phosphate binders and vitamin D analogs. Growth failure, common in children with chronic kidney disease, may improve with optimal nutrition and growth hormone therapy when indicated. Preparation for renal replacement therapy including dialysis and transplant evaluation should begin well before reaching stage 5, with preemptive transplant representing the optimal outcome for children approaching end-stage renal disease.

<image>Panel A: Diagram categorizing acute kidney injury causes as prerenal, intrinsic, and postrenal with specific examples in each category. Panel B: Blood smear photomicrograph showing schistocytes and thrombocytopenia characteristic of hemolytic uremic syndrome. Panel C: Graph depicting chronic kidney disease stages with GFR on y-axis and corresponding management requirements at each stage. Panel D: Growth chart showing height velocity improvement in child with chronic kidney disease after initiation of growth hormone therapy.</image>

Section 10: Enuresis and Voiding Dysfunction

Enuresis, the involuntary passage of urine after the age at which continence is expected, represents one of the most common concerns brought to pediatric practitioners. Nocturnal enuresis alone occurs in approximately 15% of five-year-olds, with spontaneous resolution rates of about 15% per year such that only 1% of adolescents remain affected. Despite this favorable natural history, enuresis causes significant distress to children and families, impacting self-esteem, social activities like sleepovers, and family dynamics. Understanding the classification, evaluation, and management of enuresis allows practitioners to provide effective counseling and treatment.

Enuresis is classified by timing and whether the child ever achieved sustained continence. Primary enuresis indicates the child has never been consistently dry, while secondary enuresis develops after at least six months of established continence, suggesting an acquired factor such as urinary tract infection, diabetes, psychological stress, or constipation. Monosymptomatic nocturnal enuresis involves nighttime wetting only without daytime symptoms, while non-monosymptomatic enuresis includes daytime urgency, frequency, incontinence, or voiding postponement. This distinction matters because monosymptomatic nocturnal enuresis is typically a developmental condition amenable to behavioral and pharmacologic management, while non-monosymptomatic enuresis suggests underlying bladder dysfunction requiring different evaluation and treatment approaches.

The pathophysiology of primary monosymptomatic nocturnal enuresis involves interplay between nocturnal urine production, bladder capacity, and arousal from sleep. Many affected children produce larger volumes of urine at night due to reduced nocturnal vasopressin secretion, overwhelming their functional bladder capacity. Others have smaller bladder capacity or detrusor overactivity that fails to awaken them before voiding occurs. Deep sleep and impaired arousal to bladder signals contribute in most cases, explaining why affected children often report difficulty waking even to alarms or parental attempts. Genetic factors play an important role, with approximately 75% concordance in monozygotic twins and identifiable family history in most cases. Secondary enuresis warrants evaluation for precipitating factors including urinary tract infection, new-onset diabetes, psychological stressors, or constipation.

Evaluation of enuresis begins with thorough history covering wetting pattern, daytime symptoms, fluid intake, bowel habits, developmental history, and psychosocial assessment. Physical examination should include abdominal palpation for stool burden or bladder distension, spine examination for midline defects suggesting occult dysraphism, genital examination, and neurologic assessment of lower extremities and perineum. Urinalysis rules out infection and glucosuria. Further testing is reserved for children with non-monosymptomatic symptoms, secondary enuresis, or abnormal findings on initial evaluation. Treatment begins with reassurance that enuresis is common, not the child's fault, and likely to resolve over time. Behavioral measures include fluid restriction in the evening, scheduled voiding before bed, and addressing constipation if present. Bedwetting alarms represent the most effective long-term treatment, triggering arousal at the onset of wetting to eventually condition the child to awaken to bladder fullness. Desmopressin, a synthetic vasopressin analog, reduces nocturnal urine production and provides effective short-term control for situations like sleepovers, though relapse is common upon discontinuation. Treatment of underlying constipation often dramatically improves enuresis.

<image>Panel A: Diagram illustrating the pathophysiology of nocturnal enuresis with interaction of nocturnal polyuria, bladder capacity, and arousal threshold. Panel B: Algorithm for evaluation of enuresis with decision points based on primary versus secondary and presence of daytime symptoms. Panel C: Bedwetting alarm device and sensor placement demonstration with explanation of conditioning mechanism. Panel D: Calendar reward chart example showing dry night recording with star stickers for positive reinforcement.</image>

Summary

• Hematuria evaluation distinguishes glomerular sources characterized by brown discoloration, red blood cell casts, and dysmorphic cells from non-glomerular sources with bright red color and isomorphic cells, with workup including blood pressure, repeat urinalysis, and selective laboratory testing

• Proteinuria assessment begins with first-morning specimen to exclude orthostatic proteinuria, followed by quantification using protein-to-creatinine ratio and further evaluation if persistent or nephrotic range

• Nephrotic syndrome is defined by proteinuria exceeding 40 mg/m2/hr, hypoalbuminemia below 2.5 g/dL, and edema, with minimal change disease accounting for 80% of childhood cases and responding to corticosteroid therapy in 95%

• Post-streptococcal glomerulonephritis presents 1-2 weeks after pharyngitis with tea-colored urine, edema, and hypertension, showing depressed C3 complement with excellent prognosis and supportive treatment

• IgA nephropathy causes gross hematuria concurrent with upper respiratory infection rather than after a latent period, shows normal complement levels, and has variable long-term course

• Vesicoureteral reflux grades I-V predict likelihood of spontaneous resolution, with lower grades often managed conservatively while higher grades may require surgical intervention

• Posterior urethral valves occur only in males and cause bilateral hydronephrosis detectable prenatally, with treatment by valve ablation though chronic kidney disease risk remains

• Pediatric hypertension is defined by age, sex, and height percentiles, with secondary causes including renal disease and coarctation predominating in younger children

• Hemolytic uremic syndrome presents with microangiopathic hemolytic anemia, thrombocytopenia, and acute kidney injury following bloody diarrhea from E. coli O157:H7, requiring supportive care without antibiotics

• Primary nocturnal enuresis is common and self-limited, with bedwetting alarms providing the most effective long-term treatment and desmopressin useful for short-term control

Key Terms

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