Lupus Nephritis, but Negative Serologies: How Can That Be?

Fig 2 of Pirkle et al AJKD

Fig 2 of Pirkle et al.

Invited commentary by Dr. Parmjeet Randhawa

Pirkle et al recently reported an interesting case of lupus-like membranous nephropathy in the American Journal of Kidney Diseases. The pathologic features consistent with lupus nephritis were (a) the presence of IgG, IgM, IgA, C1q, and C3 deposits by immunofluorescence (so-called full-house pattern), (b) ultrastructural evidence of immune complex deposits in subepithelial, subendothelial, and mesangial compartments, and (c) immune complex deposits in the tubular basement membranes. Clinically, this case satisfied only three of eleven clinical and laboratory criteria for systemic lupus erythematous (SLE) specified by the American College of Rheumatology (ACR), whereas at least 4 criteria are required to make a firm a diagnosis. Hence, the diagnosis of lupus-like nephropathy rather than lupus nephritis is made. The diagnostic algorithm appropriate for such cases is clearly enunciated by the authors.

In applying the diagnostic criteria for SLE to individual patients, it is important to remember that not all of the criteria need to be present concurrently. Therefore, it is necessary to obtain a thorough past medical history before making a determination as to whether SLE criteria are satisfied in any given case. A second important consideration is that while some patients do not fulfill the SLE criteria at the time of initial presentation, they do so with longer follow up. This may be the result of false negative laboratory testing, or progression of disease.

With respect to other diagnoses, the authors correctly point out that the most important element is not to miss an underlying infectious or neoplastic condition that may require specific therapy. In the case presented, the membranous nephropathy with phospholipase A2 receptor containing immune complex deposits was not further investigated. Along these lines, it should be noted that several other specific antigens have now been identified in deposits of patients with membranous nephropathy. The list of antigens incriminated includes manganese superoxidase dismutase, aldose reductase, neutral endopeptidase, and cationic bovine serum albumin. The latter protein is particularly interesting as it raises prospects of alleviating the disease by eliminating cow’s milk from the diet of an affected patient. In newborn babies, a unique condition is alloimmune neonatal membranous nephropathy, which is caused by transplacental transfer of IgG antibodies produced by mothers who are deficient in neutral endopeptidase. The actual incidence of lupus-like glomerulonephritis in these newly recognized forms of membranous nephropathy is probably low but has not yet been specifically investigated.

Parmjeet Randhawa, MD
Professor of Pathology, University of Pittsburgh Medical Center
AJKD Associate Editor

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