Case Published: July 2018
Diagnosis: Systemic Lupus Erythematosus (SLE) Nephritis, Class IV
This is a young woman presenting with two weeks of intermittent fevers, fatigue, peripheral edema, and joint pain/swelling of the wrists and ankles. Her initial laboratory studies are remarkable for pancytopenia (low levels of platelets, white blood cells, and hemoglobin/hematocrit), as well as an elevated blood urea nitrogen (BUN) and creatinine – increased from normal 3 months ago. We subsequently find evidence of both hematuria and proteinuria on her urinalysis, with red blood cell (RBC) casts in the urine sediment.
These findings raise concern for a rapidly progressive glomerulonephritis (RPGN), given the decrease in estimated glomerular filtration rate of more than 50% over a short period of time. This patient may have an underlying inflammatory, infectious, or possibly even neoplastic process. Regardless of our clinical suspicions, we should approach RPGN in a systematic way to avoid missing anything!
With our working differential for RPGN, we now utilize serologic testing and ultimately kidney biopsy to make the diagnosis. In this case we find hypocomplementemia, with low levels of both C3 and C4. This finding helps narrow our differential to immune-complex mediated disease. In particular, the low levels of both C3 and C4 in the setting of a markedly elevated anti-nuclear antibody (ANA) titer are suggestive of lupus nephritis (LN). We would also expect anti-double stranded DNA (anti-dsDNA) to be positive in the presence of LN. In fact, it has been shown that there is a correlation between anti-dsDNA levels and active kidney involvement in lupus.
So in this patient with such a high suspicion for systemic lupus erythematosus (SLE) nephritis, why bother with a kidney biopsy? Histopathology is needed for classification of lupus nephritis (LN), which is crucial for treatment planning and prognostication.
(Find more on classification, including definitions of “active” and “chronic lesions” here)
Based on our biopsy findings in this patient of proliferation of the endocapillary cells, “wire loop” capillaries due to subendothelial immune-complex deposits within the basement membrane, and crescents (proliferation of extracapillary cells), this patient would be classified as Class III or Class IV LN. As proliferation was seen in more than half of the glomeruli, our patient has Class IV.
On electron microscopy and immunofluorescence, LN has particular characteristics. The “full house” IF staining, or granular basement membrane/mesangial staining of IgG, IgA, IgM, C3, and C1q, is classic. Another clue is the presence of tubuloreticular inclusions (TRI) seen within the endothelial cell. TRIs are thought to arise from the endoplasmic reticulum (see below) and induced by interferons. They are seen in autoimmune and infectious processes including LN, HIV, and hepatitis C virus (and many others!).
Finally, treatment regimens for LN vary depending on the both patient and disease characteristics. The immunosuppressive agents that are most commonly used include glucocorticoids, mycophenolate mofetil (MMF), azathioprine, cyclophosphamide, and calcineurin inhibitors. Rheumatologists and nephrologists often work together to find the optimal treatment regimen for the lupus patient.
For more, take a look at the references below:
- Almaani S, Meara A, Rovin BH: Update on Lupus Nephritis. Clin. J. Am. Soc. Nephrol. CJN.05780616, 2016
- Parikh SV, Rovin BH: Current and Emerging Therapies for Lupus Nephritis. J. Am. Soc. Nephrol. JASN 27: 2929–2939, 2016
- Chan TM: Treatment of severe lupus nephritis: the new horizon. Nat. Rev. Nephrol. 11: 46–61, 2015