Atlas: Clinical Quiz 5
A 70-year-old woman was diagnosed with Sjögren syndrome four years ago. She also has a history of hypertension, which has recently become difficult to control. She presented with shortness of breath and was found to have pericardial effusion and a serum creatinine of 2.0 mg/dL (eGFR, 25 mL/min), elevated from baseline of 1.0 mg/dL (eGFR, 55 ml/min). Urinalysis showed microscopic hematuria with 5-10 RBCs/HPF. Urine protein/creatinine ratio was 2.5 g/g. Laboratory workup revealed an ANA of 1:2560, but dsDNA was negative. Serum C3 was low at 61 mg/dL, and C4 was unmeasurable. Rheumatoid factor was high at 400 IU/mL. ANCA test was negative. Liver function tests were normal. Serum calcium was 7.8 mg/dL. Hepatitis B and C virus serologies were negative. She weighed 170 pounds with a BMI of 30. A kidney biopsy was performed.







This case demonstrates how difficult the diagnosis of cryoglobulinemic glomerulonephritis can sometimes be. In a typical case when numerous glomerular intracapillary hyaline thrombi are present in the setting of hepatitis C virus infection, the diagnosis is easy. These intracapillary hyaline thrombi and additional glomerular deposits stain strongly for IgG, IgM, kappa, and lambda light chains, and electron microscopy reveals microtubular substructure. In this biopsy, the deposits were scant, and, in our experience, this is not unusual in cryoglobulinemic glomerulonephritis. In fact, we usually raise the possibility of underlying cryoglobulinemia if we encounter an endocapillary proliferative glomerulonephritis with paucity of immune complex deposits. The undetectable C4 levels and the high rheumatoid factor levels are laboratory findings strongly suggestive of cryoglobulinemia. In this kidney biopsy, cryoglobulinemic vasculitis was also evident, which is mostly not seen in kideny biopsies with cryoglobulinemic glomerulonephritis. However, seeing vasculitis in a kidney biopsy is rare, even in other forms of systemic vasculitides, such as in ANCA-associated vasculitides. The cryoglobulin test is frequently false-negative; therefore, a negative cryoglobulin test does not exclude the possibility of cryoglobulinemic glomerulonephritis. Cryoglobulinemic glomerulonephritis is most frequently seen in association with hepatitis C virus infection, but Sjögren syndrome is perhaps the second most common underlying etiology. This patient had Sjögren syndrome-associated type II cryoglobulinemia with associated glomerulonephritis and vasculitis.
After the biopsy, the first cryoglobulin test was negative but the repeat test was positive. After a 4-week course of rituximab, the patient’s proteinuria decreased to 0.4 g/day and her serum creatinine decreased to 1.3 mg/dL and her eGFR rose to 42 mL/min.
Post prepared by and all images courtesy of Tibor Nadasdy, MD, AJKD Blog Contributor and AJKD Kidney Biopsy Teaching Case Advisory Board member.
Please visit the Atlas of Renal Pathology II (freely available) at AJKD.org for related installments on this and other topics.
immunotactoid glomerulonephritis
Diffuse proliferative LN with Vasculitis
Interesting case
this is diffuse proliferative lupus nephritis
diffuse proliferative LN
immunotactoid glomerulonephritis.
Diffuse proliferative SLE
Immunotactoid GN
Membrano proliferative G N
Cryoglobulinimia
Cryoglobulinemicglomerulonephritis And vasculitis
The morphological aspect in HE is membranoproliferative
In EM: there are double countours with some interposition of mesangial cells and subendothelial deposits (dot like ), foot process effacement, microvillous
transformation
IF: granular deposits ( subendothelial )
MPGN + low C3 , + ve RF , Diagnoses Cryoglobulinaemic GN