IgA nephropathy (Bergers Disease)
Discussion
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
diagnosis.
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.
References:
Kusumoto Y, Takebayashi S, Taguchi T, Harada T, Naito S. Long-term
prognosis and prognostic indices of IgA nephropathy in juvenile and in
adult Japanese. Clin Nephrol. 1987;28:118-124
Levy M, Gonzalez-Burchard G, Broyer M, Dommergues JP, Foulard M, Sorez
JP, Habib R. Berger's disease in children: natural history and
outcome. Medicine. 1985;64:157-180
Yoshikawa N, Ito H, Yoshiara S, et al. Clinical course of
immunoglobulin A nephropathy in children. J Pediatr. 1987;110:555-560