IgA nephropathy (Bergers Disease)
Immunoglobulin A nephropathy (IgAN), or Berger disease, is a
glomerular disease that occurs
most often during the
second decade of
life and in adults. The most common presenting symptom is
gross hematuria following an upper respiratory tract
infection. There is generally no pain
associated with the gross hematuria, although some patients report "loin" pain.
Any child who has gross hematuria, defined as pink,
red, or brown-colored urine, must be evaluated. The first step is to
analyze the urine for the presence of red blood cells (RBCs).
The absence of RBCs in urine that is discolored indicates the presence of
hemoglobin, myoglobin, or porphyrins. If RBCs are present, as in the patient
described in the vignette, IgAN must be considered in the differential
The cause and pathogenesis of IgAN remain unclear. Although serum and mucosal IgA levels and IgA immune complexes usually are elevated, the mechanism of deposition of IgA deposits in the kidney is not yet known. The association of a preceding upper respiratory tract infection with IgAN suggests an immunologic link. Although not all patients who have IgAN present initially with gross hematuria, most eventually experience recurrent episodes of gross hematuria.
Urinalysis in any child who has gross hematuria also should assess the presence of protein (indicating renal parenchymal disease), white blood cells (suggesting either renal parenchymal disease or infection), and nitrites (suggesting urinary tract infection). It is important to note that nephrolithiasis and urolithiasis are extremely uncommon in the absence of abdominal or urethral pain. Serum electrolyte levels must be evaluated to assess renal function. Finally, renal ultrasonography should be performed to ascertain the presence of a structural malformation such as cystic disease, hydronephrosis, tumor, or obstruction.
If none of these studies reveals the source of the gross hematuria, further evaluation is necessary. The most logical next step is renal biopsy. The urgency for immediate kidney biopsy is controversial. In the absence of hypertension, proteinuria, or abnormal renal function, most pediatric nephrologists choose to observe the patient. Indeed, in the absence of proteinuria, hypertension, or renal dysfunction, most do not treat IgAN.
If IgAN is confirmed on renal biopsy, treatment options are limited. Although steroid therapy has been successful in a subset of patients who have IgAN, this treatment is of dubious advantage in the majority of patients. Therapeutic protocols that include cytotoxic agents such as cyclophosphamide and cyclosporine remain controversial. Recently, several studies have shown that fish oil (omega-3) may be beneficial in advanced stages of IgAN. The mechanism of its action is likely related to changes in renal blood flow.
The prognosis for patients who have IgAN is variable. About one third have mild disease with minimal evidence of progression. One third may experience frequent recurrences of gross hematuria, with a very slow decline in renal function over as many as 3 decades. Finally, the remaining one third will have significant proteinuria, hypertension, and renal insufficiency that eventually requires renal replacement therapy and transplantation. Angiotensin-converting enzyme inhibitor treatment should be considered for patients who have significant proteinuria. In many patients, this treatment will reduce proteinuria, thus the potential for decreased renal injury.
Alport syndrome (link), or familial nephritis, is a kidney disease caused by abnormal collagen deposition in the basement membrane of the glomerulus. This slowly progressive disease generally affects males. Alport syndrome may present with either gross or microscopic hematuria, but it is much less common than IgAN. Associated features include deafness and ocular abnormalities. Focal segmental glomerulosclerosis is a glomerular disease that typically presents with proteinuria. Hematuria may be present, but it is not the predominant feature. Hypercalciuria typically presents with hematuria, but the hematuria is usually microscopic, unless accompanied by lithiasis. Lithiasis almost always is associated with excruciating flank, abdominal, or urethral pain. Finally, postinfectious glomerulonephritis (link) usually presents with gross hematuria, but generally at least 2 weeks after an upper respiratory tract infection and often is associated with a sore throat.
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