ASN's Mission

To create a world without kidney diseases, the ASN Alliance for Kidney Health elevates care by educating and informing, driving breakthroughs and innovation, and advocating for policies that create transformative changes in kidney medicine throughout the world.

learn more

Contact ASN

1401 H St, NW, Ste 900, Washington, DC 20005

email@asn-online.org

202-640-4660

The Latest on X

Kidney Week

Abstract: SA-PO896

IgM Dominant Proliferative Glomerulonephritis (GN), Undetectable Serum C4, and Chronic Lymphocytic Leukemia (CLL) with Persistently Negative Serological Testing for Type 1 Cryoglobulins

Session Information

Category: Glomerular Diseases

  • 1402 Glomerular Diseases: Clinical, Outcomes, and Therapeutics

Authors

  • Konda, Raghunandan, The University of Alabama at Birmingham, Birmingham, Alabama, United States
  • Rizk, Dana V., The University of Alabama at Birmingham, Birmingham, Alabama, United States
  • Rajasekaran, Arun, The University of Alabama at Birmingham, Birmingham, Alabama, United States
Introduction

Cryoglobulins are immunoglobulins (Ig) that precipitate at < 37°C and dissolve on rewarming. Type I cryoglobulinaemia consists of 1 isotype of monoclonal Ig, whereas type II and type III are classified as mixed cryoglobulinaemia [include IgG & IgM]. We describe a likely longstanding type 1 cryoglobulinemia with persistently negative serological testing in a patient with chronically suppressed/undetectable C4 levels, leukocytoclastic vasculitis, IgM kappa paraproteinemia, and IgM dominance in the kidney biopsy with CLL eventually being diagnosed much later.

Case Description

87-year-old male with diabetes mellitus, chronic leukocytoclastic vasculitis, and persistently low C4 presented with AKI on CKD. Baseline Cr 1.3 mg/dL. Had serum cryoglobulins checked multiple times at different labs that were all negative. Exam sig. for purupuric lesions in LE. Cr 2.3 mg/dL, Sr albumin 3.7 g/dL, UA 1(+) protein, UPCR 340 mg/g, C3 102, C4 <1, RF 72, Sr Kappa (376) and Lambda (138) with FLC 2.7. SPEP/SIFE negative. UPEP/UIFE revealed M-spike with monoclonal IgM kappa LC. Sr cryoglobulin, HCV [Ab & Quant], CCP, and comprehensive GN screen (-). Blood cultures and testing for indolent infections including Bartonella/coxiella (-). ECHO [TTE/TEE] normal. Kidney bx revealed focal proliferative glomerulonephritis. IFTA 50%. IF: Diffuse global granular mesangial staining for IgM [3+], C3 [2+], kappa [2+], and lambda [3+]. Pronase IF negative. EM: No immune deposits. Congo red (-). Patient became sick with worsening abdominal lymphadenopathy that demonstrated IgM kappa CLL [BM Bx neg]. Serum testing for cryoglobulin again (-). Patient subsequently died.

Discussion

Testing for cryoglobulins is complicated by lack of reference range, standards, and stringency in maintaining testing temperature conditions. Despite the overall diagnosis favoring a likely an indolent Type 1 cryoglobulinemic process, our case is rare in that it was never detectable [blood, kidney, skin biopsy] and that the eventual diagnosis of CLL appeared 7 years after initial clinical manifestations. Better modalities to diagnose Type 1 cryoglobulins are therefore warranted.