A Woman with Gastrointestinal Symptoms, Anemia, and Acute Kidney Injury

Posted by • January 24th, 2014

In the latest Case Record of the Massachusetts General Hospital, a 61-year-old woman was admitted to the hospital because of vomiting, diarrhea, anemia, and acute kidney injury. Physical examination was normal. Laboratory testing and a diagnostic procedure were performed.

The causes of rapidly progressive glomerulonephritis consist of the following three large groups of diseases: anti-glomerular basement membrane (GBM) disease (Goodpasture’s syndrome); pauci-immune or antineutrophil cytoplasmic antibody (ANCA)-mediated crescentic glomerulonephritis; and the immune-complex-mediated glomerulonephritides.

Clinical Pearls

What are the most common causes of rapidly progressive glomerulonephritis?

The most common causes of rapidly progressive glomerulonephritis are the ANCA-associated vasculitides. These include granulomatosis with polyangiitis (formerly Wegener’s granulomatosis), microscopic polyangiitis, eosinophilic granulomatosis with polyangiitis (Churg-Strauss syndrome), and pauci-immune crescentic  glomerulonephritis. ANCA-associated vasculitis typically involves the kidneys and upper and lower respiratory tracts but can involve other organs, including the skin, nerves, sinuses, central nervous system, and heart, and the gastrointestinal tract. Isolated gastrointestinal involvement with vasculitis and ulcers is less common.

How are the immune-complex glomerulonephritides classified?

The immune-complex glomerulonephritides are divided into normocomplementemic and hypocomplementemic glomerulonephritis.  Diseases that are associated with normal serum complement levels include IgA nephropathy and Henoch-Schonlein purpura, which are both IgA-mediated, and fibrillary and immunotactoid glomerulonephritis.  IgA nephropathy is the most common cause of glomerulonephritis and ranges from asymptomatic hematuria and proteinuria to the nephrotic syndrome or rapidly progressive glomerulonephritis. Diseases with low complement levels include many diseases that activate the alternative complement pathway, which causes very low C3 and normal C4 levels, and very few diseases that activate the classic complement pathway, which causes a very low C4 level and a normal or mildly depressed C level. The classic diseases associated with low complement levels are systemic lupus erythematosus (SLE), membranoproliferative glomerulonephritis, poststreptococcal glomerulonephritis, shunt nephritis, bacterial endocarditis, visceral abscess, other infections, and C3 glomerulonephritis.

Table 2.Causes of Rapidly Progressive Glomerulonephritis.

Morning Report Questions

Q: What are the types of cryoglobulins?

A: Cryoglobulinemia is an immune-complex glomerulonephritis that activates the classic complement pathway. There are three types of cryoglobulins, with different underlying causes. Type I cryoglobulinemia is characterized by an IgM or IgG M component that forms a cryoprecipitate by itself; the underlying disease is typically an immunoglobulin-secreting B-cell neoplasm such as Waldenstrom’s macroglobulinemia (lymphoplasmacytic lymphoma) or plasma-cell myeloma. Type II cryoglobulinemia is characterized by an IgM or IgG M component that has rheumatoid-factor activity against polyclonal IgG. Type II cryoglobulinemia is also associated with lymphoplasmacytic lymphoma or myeloma, hepatitis C virus (HCV) infection, and rheumatologic disorders. Type III cryoglobulinemia is characterized by a polyclonal IgM or IgG rheumatoid factor that binds polyclonal IgG; it tends to be associated with infections such as HCV, hepatitis B virus, and the human immunodeficiency virus and, less commonly, with endocarditis, SLE, and other rheumatologic diseases.

Q: What are pathognomonic findings on renal biopsy for cryoglobulinemic glomerulonephritis?

A: Glomerular pseudothrombi are pathognomonic for cryoglobulinemic glomerulonephritis. Key features supporting a diagnosis of cryoglobulinemic glomerulonephritis are the predominance of macrophages in the glomerular infiltrate and a tubular substructure on electron microscopy. Concomitant vasculitis is also present, which has been reported in about 22% of renal-biopsy specimens in a small case series involving patients with similar laboratory findings. The diffuse glomerular involvement, lack of interstitial fibrosis, and minimal duplication of the glomerular basement membrane are features suggestive of a highly active acute process with minimal chronicity.

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