G LOMERULONEPHRITIS AND H EMATURIA

G LOMERULONEPHRITIS Glomerular injury may result from immunologic injury (poscstreptococcal acute glomerulonephritis, PSGN), inherited disease (Alporr syndrome), or toxins (hemolytic uremic syndrome). Children with glomerular hematuria and any other cardinal fearures of glomerular injury (proteinuria, hypertension, edema,oliguria,renal insufficiency) are considered to have glomerulonephritis (GN).

Immune-mediated inflammation is the mechanism for proliferative GN, of which PSGN is the most common form. PSGN usually occurs during or after streptococcal pharyngitis or impetigo. Immunologic reaction to bacterial proteins trapped in the glomerular capillary wall, followed by insitu activation of complement, leads to cell proliferation and glomerular injury.

Only certain nephritogenic strains of group A streptococcus cause this reaction. Age, gender, socioeconomic status, and genetic predisposition affect likelihood of PSGN. It occurs most frequently in children 2 to 12 years of age and more often in boys.

CLINICAL MANIFESTATIONS OF PSGN PSGN may present with hematuria (gross in 65%) edema (75%) and hypertension (50%). Acute renal insufficrency may occur. Manifestations develop 5 to 2I days (average 10 days) after nephritogenic streptococcal infections. Many children still have active infection at time of clinical renal manifestations. Oliguria, renal insufficiency, and consequent hypertension may lead to complications such as heart failure, seizures, and encephalopathy.

Urinary tract infection (UTI) is the most common identifiable cause of hematuria in children

Hematuria without casts is seen in sickle cell trait or disease, after strenuous exercise, and after renal trauma. Coagulopathies can lead to hematuria.

Hypercalciuria can cause isolated hematuria in children; 25%to 30% of children with isolated hematuria have elevated urinary calcium excretion. Urolithiasis may be associated with asymptomatic hematuria or with urinary tract symptoms, such as pain.

I G A NEPHROPATHY The most common from of chronic GN in children is IgA nephropathy (IgA GN), which often presents with microscopic hematuria or recurrent gross hematuria shortly after onset of upper respiratory infection. The course of IgA GN is usually benign, and occurs more frequently in boys and in school age children and young adults. IgA GN may progress to end-stage renal disease (ESRD) in up to 3o% of children, particularly in patients with proteinuria or renal insufficiency at presenrarion.

Schonlein-Henoch purpura nephritis, lupus nephritis, and vasculitis-associated GN often have hematuria at presentation.

A SYMPROMATIC MICROSCOPIC HEMARURIA Undiagnosed structural disorders Mild forms of GN Benign familial hematuria Alport slmdrome

B ENIGN FAMILIAL HEMATURIA Benign familial hematuria is a relarively common, nonprogressive usually autosomal dominant disorder, characterized by thinning of the glomerular basement membrane (GBM).

A LPORT SYNDROME Alport syndrome may present with asymptomatic microscopic hematuria early in life. Several patterns of inheritance and several mutated genes are associated with significant GBM disruption over time. The most common form includes progressive high-tone bilateral neurosensory deafness and progressive renal failure during adolescence and young adulthood, particularly in males.

R APIDLY PROGRESSIVE GLOMERULONEPHRITIS (RPGN) May present with rapidly progressingrenal insufficiency, edema, gross hematuria, andhypertension (HTN). Renal biopsy shows glomerular epithelial cell proliferation with crescents. RPGN is more common in late childhood and adolescencents.It may be idiopathic or associated with various conditions (MPGN, PSGN, IgA GN, antineutrophilic cytoplasmic ancibody associated vasculitis, and Schonlein-Henoch purpura).

DIAGNOSTIC STUDIES Hematuria can be gross or microscopic. A positive urine dipstick requires microscopy to identify RBCs. Microscopic hematuria is defined as more than 3 ro 5 RBCs per high-power field in freshly voided and centrifuged urine.

E VALUATION OF A C HILD WITH H EMATURIA 1. Complete history and physical examination (particularly blood pressure, optic discs, skin, abdomen, genitalia) 2. Confirmarion of true hematuria by urine microscopic examination 3 Urine culcure 4 Urine calcium, protein, creatinine 5. Complete blood count including platelets, serum electrolytes, BUN/serum crearinine (calculate crearinine clearance),calcium, total protein and albumin 6. Streptozyme,C 3, C4, ANA 7. Renal ultrasonography 8. Renal biopsy in selected cases

THERAPY Specific rherapy for PSGN involves dietary sodium restriction, diuretics,a nd antihypertensive agents as needed. Therapies for children with other forms of GN are still evolving. In some cases, corticosteroid, immunosuppressive, and/or anti-inflammatory agents may be useful, often for extended treatment courses. Treatment with angiotensin-converting enzyme inhibitors or angiotensin receptor blockers may minimize proteinuria and glomerular hyperperfusion.

PROGNOSIS AND PREVENTION PSGN is a relatively benign diseasei n children. In typical cases proteinuria and edema decline quickly (in 5-10 days). Microscopic hematuria may persist for months or even years; over 95% of children recover completely. Treating the streptococcal infection does not prevent PSGN; however, if the patient still has active streptococcal infection, antibiotic treacmen its warranted. Few children with PSGN or other forms of postinfectious GN progress to ESRD.

Children with IgA GN and other forms of chronic GN have a real risk of progression to ESRD. In IgA GN, presence of persistent, heavy proteinuria, hypertension, reduced GFR, and severe glomerular lesions on biopsy have been associated with poor outcomes. Recurrence of IgA deposits in transplanted kidneys is often observed, but does not significantly alter graft survival.

The prognosis for renal recovery in other forms of chronic GN and in RPGN is variable and related to the disorder and disease severity at diagnosis.