Chapter 504 Isolated Glomerular Diseases with Recurrent Gross Hematuria
Approximately 10% of children with gross hematuria have an acute or a chronic form of glomerulonephritis that may be associated with a systemic illness. The gross hematuria, which is usually characterized by brown or cola-colored urine, may be painless or associated with vague flank or abdominal pain. Presentation with gross hematuria is common within 1-2 days after the onset of an apparent viral upper respiratory tract infection in immunoglobulin A (IgA) nephropathy, and typically resolves within 5 days. This relatively short period contrasts to a latency period of 7-21 days occurring between the onset of a streptococcal pharyngitis or impetiginous skin infection and the development of poststreptococcal acute glomerulonephritis. Gross hematuria in these circumstances can last as long as 4-6 wk. Gross hematuria can also be seen in children with glomerular basement membrane (GBM) disorders such as hereditary nephritis (Alport syndrome [AS]) and thin GBM disease. These glomerular diseases can also manifest as microscopic hematuria and/or proteinuria without gross hematuria.
504.1 Immunoglobulin A Nephropathy (Berger Nephropathy)
IgA nephropathy is the most common chronic glomerular disease. It is characterized by a predominance of IgA immunoglobulin within mesangial glomerular deposits in the absence of systemic disease (e.g., symptomatic systemic lupus erythematosus or Henoch-Schönlein purpura). Diagnosis requires renal biopsy, which is performed when clinical features warrant confirmation of the diagnosis or characterization of the histologic severity, which might affect therapeutic decisions.
Pathology and Pathologic Diagnosis
Focal and segmental mesangial proliferation and increased mesangial matrix are seen in the glomerulus (Fig. 504-1). Renal histology demonstrates mesangial proliferation that may be associated with epithelial cell crescent formation and sclerosis. IgA deposits in the mesangium are often accompanied by C3 complement (Fig. 504-2).
Figure 504-1 Light microscopy of immunoglobulin A nephropathy demonstrating segmental mesangial proliferation and increased matrix (×180).
Figure 504-2 Immunofluorescence microscopy of the biopsy specimen from a child with episodes of gross hematuria demonstrating mesangial deposition of immunoglobulin A (×150).
IgA nephropathy is an immune complex disease that appears to be caused by abnormalities in the IgA immune system. The abnormalities identified in the IgA immunoglobulin system have also been observed in patients with Henoch-Schönlein purpura and lends support to the hypothesis that these two diseases are part of the same disease spectrum. Familial clustering of IgA nephropathy cases suggests the importance of genetic factors. Genome-wide linkage analysis suggests the linkage of IgA nephropathy to 6q22-23 in multiplex IgA nephropathy kindreds.
Clinical and Laboratory Manifestations
IgA nephropathy is seen more often in male than in female patients. Though there are rare cases of rapidly progressive forms of the disease, the clinical presentation of childhood IgA nephropathy is often benign in comparison to that of adults. IgA nephropathy is an uncommon cause of end-stage renal failure during childhood. A majority of children with IgA nephropathy in the USA and Europe present with gross hematuria, whereas microscopic hematuria and/or proteinuria is a more common presentation in Japan. Other types of presentation include acute nephritic syndrome, nephrotic syndrome, or a combined nephritic-nephrotic picture. Gross hematuria often occurs within 1-2 days of onset of an upper respiratory or gastrointestinal infection, in contrast to the longer latency period observed in acute postinfectious glomerulonephritis, and may be associated with loin pain. Proteinuria is often <1000 mg/24 hr in patients with asymptomatic microscopic hematuria. Mild to moderate hypertension is most often seen in patients with nephritic or nephrotic syndrome but is rarely severe enough to result in hypertensive emergencies. Normal serum levels of C3 in IgA nephropathy help to distinguish this disorder from poststreptococcal glomerulonephritis. Serum IgA levels have no diagnostic value because they are elevated in only 15% of pediatric patients.
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