I was amazed to see this paper published in Pediatrics--the errors here are so basic it is difficult to understand what type of peer review the paper had. The following was sent as a letter to the editor. The journal chose not to publish the letter, after a response from the authors which basically said that they knew how to diagnose APSGN and that fancy lab tests like C3 levels aren't easily obtained in their center. And anti-C1q antibody titers are???

There are several problems with the data in the recent study by Kozyro et al (1), but for the practitioner the most serious relate to the children in the report said to have acute post-streptococcal glomerulonephritis (ASPGN).

To begin with, there are really no data in the report which can be used to support the diagnosis of ASPGN in any of the children. The authors indicate that the diagnosis was based upon the presence of hematuria, proteinuria, edema, and an elevated ASO titer. This is clearly inconsistent with contemporary practice. The sine qua non for making the diagnosis of APSGN is the demonstration of hypocomplementemia (i.e. a decreased serum concentration of C3) acutely, with normalization within several weeks. It is the rare child in whom hypocomplementemia does not occur (2). Elevations in streptococcal serology, however, are common in childhood, and a wide variety of chronic glomerulonephritides are exacerbated by respiratory infections (3). Thus, the specificity of an elevated ASO titer for APSGN is very low. Although renal biopsies are rarely employed in establishing the diagnosis of APSGN, when this does become necessary the characteristic pathologic features are best seen by immunohistochemistry and ultrastructure (electron microscopy) (4). Light microscopy alone is hardly ever sufficient to establish a diagnosis of APSGN with certainty; the single child in this study said to have APSGN who underwent biopsy had “endocapillary glomerulonephritis”, a pathologic description which is not specific for anything.

With this background, the primary focus of the study by Kozyro et al should be examined. The authors demonstrated that many children with “APSGN” had antibodies against C1q, and that these antibodies seemed to correlate with severe disease, as defined by hypertension and “more pronounced proteinuria”. The antibodies were also uniformly found in children who did not show “complete spontaneous resolution”, although this is not clearly defined in the text.

The problem with this observation is that it has been known for nearly two decades that anti C1q antibodies are found in a chronic glomerulonephritis of childhood, membranoproliferative glomerulonephritis (MPGN) (5), which is commonly confused with APSGN. These antibodies have been well studied from the standpoint of their IgG subclass restriction, and their immunochemical differences to anti C1q antibodies in SLE have been carefully examined (6).

In the absence of more detailed clinical and laboratory information, it seems most reasonable to conclude that some, if not all, of the children in this series with chronic disease and elevated C1q antibodies said to have APSGN actually had MPGN. The distinction between these disorders is not simply a matter of nephropathologic esoterica. It has very important implications. Untreated, MPGN may have a dismal prognosis in childhood, with a high propensity to evolve into end stage renal disease (ESRD). There is excellent evidence that corticosteroids in a high-dose, alternate day regimen are useful in attenuating this course.

On the other hand, APSGN is a self-limited condition in children, and no treatment other than supportive measures is recommended. Studies which have used appropriate diagnostic criteria and excellent follow up have uniformly demonstrated that the long-term outcome of APSGN is excellent, with virtually no risk of ESRD (7). Thus, the report of Kozyro et al (1) is doubly flawed. It incorrectly suggests that a chronic course and poor outcome is not uncommon in ASPGN. It fails to recognize a potentially avoidable cause of ESRD by misdiagnosing a chronic glomerulopathy.

1. Kozyro, I, Perahud, I, Sadallah, S, Sukalo, A, Titov, L, Schifferli, J. Clinical value of autoantibodies against C1q in children with glomerulonephritis. Pediatrics 2006;117:1663-1668. 2. Strife, CF, McAdams, AJ, Mcenery, PT, Bove, KE, West, CD. Hypocomplementemic and normocomplementemic acute nephritis in children: a comparison with respect to etiology, clinical manifestations, and glomerular morphology. J Pediatr 1974;84:29-38. 3. Masuda, M, Nakanishi, K, Yoshizawa, M, Iijima, K, Yoshikawa, N. Group A streptococcal antigen in the glomeruli of children with Henoch Schonlein nephritis. Am J Kidney Dis 2003; 41:366-370. 4. Sorger, K, Gessler, U, Hubner, FK, Kohler, H, Schulz, W, Stuhlinger, W, Thoenes, GH, Thoenes, W. Subtypes of acute postinfectious glomerulopephritis. Synopsis of clinical and pathological features. Clin Nephrol 1982; 17:114-128. 5. Strife, CF, Leahy, AE, West, CD. Antibody to a cryptic, solid phase C1q antigen in membranoproliferative nephritis. Kidney Int 1989;35:836-842. 6. Prada, AE, Strife, CF. IgG subclass restriction of autoantibody to solid phase C1q in membranoproliferative and lupus glomerulonephritis. Clin Immunol Immunopathol 1992;63:84-88. 7. Potter, EV, Lipschultz, SA, Abidh, S, et al. Twelve to seventeen-year follow-up of patients with poststreptococcal acute glomerulonephritis in Trinidad. N Engl J Med 1982; 307:725.