MKSAP Quiz: Lower extremity edema and fatigue
A 29-year-old man is hospitalized for lower extremity edema and fatigue that has progressed over the past 6 months. Laboratory studies document kidney failure. Following a physical exam, additional lab studies, and kidney biopsy, results of which tests will most likely explain this patient's findings?
A 29-year-old man is hospitalized for lower extremity edema and fatigue that has progressed over the past 6 months. Laboratory studies document kidney failure. History is notable for obesity. He has a remote history of intravenous drug use and a 5-year history of multiple sex partners (men and women). He takes no medications.
On physical examination, the patient is afebrile, and blood pressure is 148/94 mm Hg; other vital signs are normal. BMI is 38. There is no rash. There is pitting edema in the lower extremities to the ankles bilaterally. The remainder of the physical examination is unremarkable.
Laboratory studies:
| C3 | 60 mg/dL (600 mg/L) |
| C4 | 7.0 mg/dL (70 mg/L) |
| Creatinine | 2.8 mg/dL (247.5 µmol/L) |
| Urinalysis | 3+ blood; 3+protein |
| Urine protein-creatinine ratio | 2900 mg/g |
Kidney biopsy shows membranoproliferative glomerulonephritis on light microscopy, with immunofluorescence microscopy showing 3+ staining for IgG, 1+ staining for IgM, 2+ staining for C1q, and 2+ staining for C3.
Results of which of the following tests will most likely explain this patient's findings?
A. Genetic mutations in alternative complement pathway proteins
B. Hepatitis B surface antigen and surface antibodies
C. Hepatitis C antibodies
D. HIV antibodies
MKSAP Answer and Critique
The correct answer is C. Hepatitis C antibodies. This content is available to MKSAP 18 subscribers as Question 81 in the Nephrology section. More information about MKSAP is available online.
The most appropriate test to perform next is measurement of hepatitis C antibodies. This patient presents with glomerulonephritis (elevated serum creatinine level, hematuria, and subnephrotic proteinuria), which shows a membranoproliferative (MPGN) pattern on kidney biopsy. The new approach to MPGN lesions is a bifurcation based on the pattern of staining on immunofluorescence microscopy. The more common pattern, as seen in this patient, is immune-complex deposition with the presence of both immunoglobulin (IgG, IgM, and/or IgA) and complement (C1q and/or C3) on immunofluorescence, which infers that the classical pathway has been activated by an inciting cause or event that generally falls into one of three major categories: infectious, autoimmune, or malignancy associated. The most common is infectious, specifically infection with hepatitis C virus (HCV).
When an MPGN lesion on immunofluorescence microscopy shows only C3 staining (that is, without immunoglobulin or C1q staining), this extremely rare finding is suggestive of an antibody-independent means of complement activation and points to hyperactivity of the alternative complement pathway. In these C3 glomerulopathies, named based on the isolated C3 staining pattern seen on immunofluorescence, screening for genetic abnormalities in alternative complement pathway proteins is an appropriate part of the diagnostic evaluation.
Hepatitis B virus infection and HIV infection have been linked to glomerular diseases, but these are classically associated with the nephrotic syndrome, specifically membranous glomerulopathy with hepatitis B virus infection and focal segmental glomerulosclerosis with HIV infection.
Key Point
- An immune-complex membranoproliferative glomerulonephritis is the classic form of kidney involvement seen in patients with hepatitis C virus infection.