Glomerular Disease Clinical Case Review

In this video, Craig Gordon, MD, nephrologist at Tufts Medical Center and associate professor of medicine at Tufts University School of Medicine, discusses baseline characteristics in a case of lupus nephritis:

Editor’s note: The following is an automatically generated transcript of the above video.

"We are going to be speaking for the next 30 or so minutes about a case of lupus nephritis and facing the ongoing current questions about management. This is a patient seen recently who's a 31-year-old woman with known lupus without lupus nephritis, who was under chronic management with hydroxychloroquine and prednisone as needed for flares of arthritis. She had no prior history of kidney diseases and presented to the hospital for the relatively acute onset of abdominal pain. Was seen by rheumatology who thought this might be consistent with lupus enteritis and recommended pulse IV methylprednisolone, which was given at one gram daily with a plan for three doses.

The inpatient service recognized however, that she had a low serum albumin of 2.6 grams per deciliter, and upon taking history, the patient reported presence of foamy urine but no macroscopic hematuria. Her GFR was estimated based on a creatinine of 0.71 to be 117 mls per minute per 1.73 m². So workup of the etiology of the possible proteinuria given the foamy urine and low albumin revealed a C3 level that was low at 55, C4 was low at 10, and an anti-double stranded DNA level was elevated at 185. Review of her urinalysis revealed 3+ protein in the urine, 1+ blood, and the presence of 10 to 20 red cells per high power field. When the urine sediment was investigated, there was presence of abundant, was described, oval fat bodies, a few granular casts, numerous WBC, but no RBC or WBC casts. Quantification of her urine protein revealed 15.4 grams per gram.

So at this point, the interpretation was that the low albumin and proteinuria likely represented nephrotic syndrome and that this argued for the possibility of class V lupus nephritis or the membranous lupus lesion. I'll go over these for those less familiar with the classification of lupus nephritis in the next few slides, but that the low C3 and low C4 as well as the elevated anti-double stranded DNA might fit better for a class III or class IV lupus nephritis, a proliferative lupus nephritis lesion. So it really wasn't clear what was occurring with the patient.

I'm going to review these findings as we move towards an eventual kidney biopsy. So just a very simplified version of the ISN/RPS histopathology classification of lupus. So class III lupus is focal proliferative lupus nephritis where fewer than 50% of glomeruli are involved by light microscopy. And class IV is a diffuse proliferative lupus nephritis where greater than 50% of glomeruli are involved. Clinically, these patients generally have hematuria and proteinuria, perhaps less likely to have nephrotic range proteinuria or nephrotic syndrome, but that can be seen. They generally do have hypertension and it's typical for the GFR to be decreased either modestly or substantially. When patients undergo laboratory evaluation, we classically see low C3 and C4 complement values and elevated double stranded DNA and as I alluded to earlier, these patients can also have mixed lesions with a mixture of class III or IV with class V, which I'll demonstrate on the next slide. And this is usually patients with a mixed nephritic and nephrotic syndrome.

You can see presented here on the right side of the slide are a cartoon representing class III with a modest involvement. This is a mockup of electron microscopy and you can see here with class IV, there's much more marked deposition of electron dense deposits, so it's a more severe lesion generally. When one turns to class V lupus, this is membranous lupus. These patients clinically generally have either nephrotic range proteinuria or more commonly even nephrotic syndrome. They can have microscopic hematuria, but their GFRs are usually normal or near normal. And laboratory studies usually reveal normal complement levels and normal anti-double stranded DNA levels. And when [we] turn] to the pathology, there's usually a diffuse thickening of the glomerular basinal membrane on light microscopy, LM, and subepithelial immune deposits on immunofixation or electron microscopy.

Turning to our patient, she was hospitalized and a kidney biopsy was recommended. I think based on her clinical picture, there was a concern that she would have Class V lupus, given the nephrotic syndrome type presentation, but also given the consumed complements and elevated anti-double stranded DNA, there was some consideration that she might also have a class III or IV lesion. And in fact, although I don't have her slides here visually, her biopsy specimen revealed a combination of class IV and class V lupus.

So as you can see, there was thickening of the glomerular basal membrane with spike formation across all glomeruli. That's the class V lesion. But there was acute and active proliferative lesion seen in about 50 to 60% of glomeruli, so somewhat exceeding the 50% cutoff, and this is how the pathologist arrived at class IV. When we turned to immunofluorescent microscopy, there was full house staining, and so strong staining for IgG, IgA, IgM, C3 and C4 complement, as well as C1q. And when we turned to electron microscopy, electron dense deposits were visualized in the subepithelial and intramembranous locations which fit well for the membranous part of the lesion, with smaller but still present subepithelial deposits."