Hypercalciuria and Urolithiasis

Hypercalciuria can occur with low, normal, or high serum calcium levels. In eucalcemic patients, the most common cause is idiopathic; other causes include immobilization, Cushing’s syndrome, distal renal tubular acidosis, and Bartter’s syndrome. Disorders associated with hypercalcemia include hyperparathyroidism, vitamin D intoxication, hypophosphatasia, tumors, and immobilization bone resorption. Rare familial abnormalities of renal calcium channels are the cause of hypercalciuria with hypocalcemia. Hypercalciuria is the most common cause of stone disease.

Idiopathic hypercalciuria typically presents with asymptomatic microscopic hematuria. Stones can reveal their presence in a variety of ways to include dysuria, gross hematuria. and renal colic. Renal ultrasound or spiral computed tomography (CT) should be considered. Stones may be found incidentally after imaging is done for other reasons (e.g., radiographs for constipation). Radiographs can detect radiopaque stones but not those formed by uric acid.

The initial screening test for hypercalciuria is a urine calcium-to-creatinine ratio on a random urine sample. A ratio of greater than 0.2 in older children and adults is highly suggestive of hypercalciuria, with higher values in infants and young children. Confirmation should be obtained by a 24-hour urine collection with an excretion of greater than 4 mg/kg/24 hours. Urine from this collection should be tested for cystine, citrate, oxalate, phosphorus, and uric acid excretion as well. The collection is difficult in younger children, however. Serum chemistries, including calcium, phosphorus, magnesium, uric acid, urine pH, and renal function, should also be obtained. A detailed family history for stone disease, diet history, and evaluation of medications and nutritional supplements should be sought. Recovery of a stone should be attempted for analysis. Stones caused by infection are rare in children.

Management of these patients is twofold (Figure 61-1). Pain management should be optimized. Surgical intervention or lithotripsy is indicated in cases of urinary obstruction or recurrent stones with superimposed urinary tract infections (UTIs). After the cause has been determined, therapy to prevent stone recurrence can be implemented; this includes increased fluid intake to ensure dilute hypotonic urine, dietary manipulation, and drug therapy in some cases.

Figure 61-1 Kidney stones.

Medications

Microscopic hematuria caused by drug exposure is not uncommon. Although some medications are commonly used in children, most are not. Gross hematuria associated with cyclophosphamide can be severe in some cases.

Glomerulonephritis

All forms of glomerulonephritis are discussed in Chapter 62.

Trauma

Traumatic injury to the urogenital tract is frequently seen with blunt force trauma and may be life threatening, depending on its severity. The presence of hematuria with minimal traumatic injury is highly suggestive of anatomic abnormalities of the kidney such as polycystic kidney disease.

Hematuria associated with renal trauma requires evaluation by CT scan, magnetic resonance imaging, or renal ultrasound. Urologic evaluation should be obtained before placement of a urethral or bladder catheter in cases of lower urinary tract trauma.

Most renal contusions or lacerations can be managed conservatively; however, significant lacerations of the kidney or injury to the collecting system or lower urinary tract may require emergent surgical intervention.

Malignancy

Wilms’ tumor is the most common childhood malignancy of the kidney and is discussed further in Chapter 53. Microscopic hematuria is more commonly found than grossly bloody urine, but hematuria as the presenting sign of Wilms’ tumor is rare.

Hematologic Causes

Hematuria commonly occurs with sickle cell hemoglobinopathy. Affecting patients with either sickle cell disease or sickle cell trait, it is thought to be caused by sickling and sludging of RBCs in the renal medulla. Typically painless and occurring in adolescent boys, it can be precipitated by trauma, exercise, dehydration, or infection. Papillary necrosis is also seen with severe dehydration and renal infarction.

Hematuria is rarely the sole finding in a patient with a coagulopathy. However, coagulopathies should be investigated in patients without another source for painless, gross hematuria and a history of bruising/bleeding, or a family history of a bleeding diathesis.

Alport Syndrome

Alport syndrome is a hereditary nephritis associated with sensorineural hearing loss. Alport syndrome presents with persistent or recurrent microscopic or gross hematuria. It is further discussed in Chapter 62.

Benign Familial Hematuria

This disorder is defined by usually autosomal dominant transmission of persistent hematuria without proteinuria, hearing loss, or progressive renal disease.

This is a diagnosis of exclusion based on family history. Hematuria detected in the parents’ or siblings’ urine can support the diagnosis that is only confirmed by renal biopsy. Biopsy shows thin basement membranes in most patients.

Loin Pain-Hematuria Syndrome

This syndrome is defined by recurrent episodes of pain in the lower abdomen with gross or microscopic hematuria usually occurring in women between 20 and 40 years of age, but it may occur in younger patients. The diagnosis is one of exclusion after investigating for other etiologies. There is often a psychological component. The usual management is pain control.

Urethrorrhagia

Painless terminal hematuria, or bloody spots in the underwear, occurring in boys between 4 and 17 years of age defines this process. Dysuria is present in 30%. Symptoms usually resolve in 2 weeks to 3 years in an average of 10 months. Complete resolution occurs in 92% overall. Treatment is watchful waiting after other causes of gross hematuria have been discounted. Cystoscopy should be avoided because urethral stricture may occur.

History

A complete history is essential to guiding the diagnostic evaluation of hematuria.

Physical Examination

The examination of the patient should focus on the following:

Diagnostic Modalities

Radiographic imaging is always indicated for evaluation of gross hematuria in the absence of RBC casts and proteinuria. Ultrasound evaluation of the kidneys and bladder should be part of the initial evaluation of hematuria unless the patient has isolated microhematuria. Magnetic resonance urography is useful for delineating the anatomic structure of the collecting systems as well as for defining functional obstructions. CT scans also provide valuable anatomic information. Additional studies such as nuclear scans, cystoscopy, angiography, or renal biopsy should be considered in consultation with a subspecialist.

Benign Conditions

Transient Proteinuria

Transient proteinuria is unrelated to renal disease and resolves when the inciting factor disappears. It is rarely greater than 100 mg/dL on the dipstick. Febrile proteinuria usually appears with the onset of fever and resolves by 10 to 14 days. Proteinuria that occurs after exercise usually abates within 48 hours. Transient proteinuria seen with fever, exercise, and congestive heart failure is caused by hemodynamic alterations in renal blood flow that increases the passage of proteins across the glomerular basement membrane (Figure 61-4).

Figure 61-4 Histology and fine structure of renal corpuscle.

Pathologic Conditions

Phase I Workup

The initial workup should begin with a complete history and physical examination. The physician should elicit history of recent infections (pharyngitis, impetigo), UTIs, oliguria or hematuria, and family history of renal disease. The physical examination should be focused on looking for hypertension (glomerulonephritis), edema (nephrotic syndrome), rash or arthritis (vasculitis), and short stature (chronic renal disease). Laboratory investigations in this phase should include a urine dipstick (ambulatory and recumbent), a urine analysis including microscopic examination, and a random urine protein-to-creatinine ratio.

Qualitative Protein Detection

The dipstick measures the concentration of protein in urine. A urine sample is considered positive for protein if it measures 1+ or greater when the specific gravity of urine is less than 1.015 or 2+ or greater when the specific gravity is greater than 1.015. A child is said to have persistent proteinuria if the dipstick is positive for protein on two of three random urine samples collected at least 1 week apart. The following can cause false-positive results on dipstick analysis: alkaline urine (pH >7.0), prolonged immersion, placing the strip directly in the urine stream, cleansing of the urethral orifice with quaternary ammonium compounds before collecting the sample, pyuria, and bacteriuria. False-negative results can occur when the urine is too dilute (i.e., the specific gravity is <1.005) or when the patient excretes abnormal amounts of proteins other than albumin.

Quantitative Protein Detection

A timed urine collection for protein quantitation is essential to establish the degree of proteinuria. A 24-hour urine collection can be done by asking the child to void as soon as he or she wakes up and discarding the specimen; then every void should be collected for the next 24 hours, including the first void the next morning. In clinical practice, it is difficult to obtain timed urine collections in children. A random urine specimen can be analyzed for protein and creatinine concentration. Multiplying the random protein to creatinine ratio by 0.63 gives an estimated 24-hour total protein content in g/m²/d.

Phase II Workup

See Figure 61-5 for an evaluation algorithm. Split urine samples should be collected, and a 24-hour urinary protein level should be obtained.

Figure 61-5 Suggested approach for the evaluation of proteinuria.

Phase III Workup

If the initial workup suggests the presence of an underlying renal disease, a referral to a pediatric nephrologist should be made. A referral should be made in the following situations:

The nephrologist may perform a renal biopsy to define the etiology.

Most cases of proteinuria in children can be managed by a primary care physician at times in consultation with a pediatric nephrologist. Long-term follow-up is important because the prognoses in some of the conditions are not well defined.