In their case presentation, Schnabl et al. ask readers to consider approaches to an adult with the diagnosis of nephrotic syndrome, the primary and secondary renal pathologies that may be seen in adult glomerular disease, and tests that might be ordered to help differentiate the cause of this patient’s renal disease.
Most adult patients with nephrotic syndrome require a kidney biopsy for a pathologic diagnosis to be made (the one common exception being presumed diabetic nephropathy). Clues to diagnosis from the results of laboratory testing may help limit the differential but are not a substitute for biopsy, except in situations in which a biopsy is too risky (e.g., a bleeding tendency).
The commonest causes of primary nephrotic syndrome are membranous nephropathy, focal segmental glomerulosclerosis, and minimal-change disease. No laboratory tests are very helpful in distinguishing these diseases.
About 30% of cases of nephrotic syndrome have a secondary cause in adults. Autoimmune disease (lupus), infections (hepatitis B and C, malaria), malignancy (lymphoma), drugs (gold, pamidronate, and so forth), monoclonal gammopathy (primary amyloidosis), and chronic inflammatory conditions (secondary amyloidosis) are some of them.
The urinalysis findings of blood and red blood cell casts strongly suggest that the pathologic process is either proliferative or necrotizing. Therefore, nonproliferative lesions (such as diabetic nephropathy, amyloidosis, and secondary minimal-change disease, membranous nephropathy, or focal segmental glomerulosclerosis) are unlikely.
The presence of hypocomplementemia makes necrotizing processes such as antineutrophil cytoplasmic antibody–associated diseases (such as Wegener granulomatosis and microscopic polyangiitis) unlikely. Proliferative lupus nephritis (class III and IV), hepatitis C–associated cryoglobulinemia, and postinfectious glomerulonephritis would be the most likely diagnoses. All are associated with hypocomplementemia. Postinfectious glomerulonephritis does not usually present as nephrotic syndrome but should be included in the differential. The key laboratory tests for this patient are therefore for serum complements, hepatitis C viral load, antinuclear antibodies, anti-DNA antibodies, and serum cryoglobulins. Hepatitis B and HIV should also be evaluated, given the history of HCV infection.
Author Contributions: All authors confirmed they have contributed to the intellectual content of this paper and have met the following 3 requirements: (a) significant contributions to the conception and design, acquisition of data, or analysis and interpretation of data; (b) drafting or revising the article for intellectual content; and (c) final approval of the published article.
Authors’ Disclosures of Potential Conflicts of Interest: No authors declared any potential conflicts of interest.
Role of Sponsor: The funding organizations played no role in the design of study, choice of enrolled patients, review and interpretation of data, or preparation or approval of manuscript.
- © 2009 The American Association for Clinical Chemistry