Kidney Week

Abstract: SA-PO0787

The Cryoglobulin-Negative Paradox: Renal-Limited Cryoglobulinemic Glomerulonephritis (GN) Revealing Monoclonal Gammopathy of Renal Significance (MGRS)

Session Information

• Glomerular Diseases: Lupus Nephritis, Monoclonal Gammopathy-Related Disease, and Transplantation
  October 24, 2026 | Location: Exhibit Hall A, Convention Center
  Abstract Time: 10:00 AM - 12:00 PM

Category: Glomerular Diseases

• 1402 Glomerular Diseases: Clinical, Outcomes, and Therapeutics

Authors

• Abdallh, Amjed Mohammed osman, Dubai Hospital, Dubai, United Arab Emirates

Amjed Mohammed osman Abdallh, MD, MBBS

• Soliman, Malaz Noralla, Dubai Hospital, Dubai, United Arab Emirates

Malaz Noralla Soliman, MD, MBBS

• Siddege, Waleed, Dubai Hospital, Dubai, United Arab Emirates

Waleed Siddege, MD, MBBS, MSc

• Mohan, Dhanya, Dubai Hospital, Dubai, United Arab Emirates

Dhanya Mohan, MD

• Alalawi, Fakhriya, Dubai Hospital, Dubai, United Arab Emirates

Fakhriya Alalawi, MD, MSc

• Alhadari, Amna Khalifa, Dubai Hospital, Dubai, United Arab Emirates

Amna Khalifa Alhadari, PhD

Introduction

Cryoglobulinemic glomerulonephritis is classically associated with circulating cryoglobulins; However, up to 27% of cases may be seronegative. These cases are renal-limited and may delay recognition of underlying monoclonal gammopathies. We report a compelling case of severe, seronegative Cryoglobulinemic GN secondary to Monoclonal Gammopathy of Renal Significance, highlighting the critical role of renal biopsy and early clone-directed therapy.

Case Description

A 57-year-old woman with long-standing rheumatoid arthritis presented with edema, vomiting, and fatigue. Labs showed AKI, creatinine 2.43 mg/dL, eGFR22.6 ml/min, nephrotic proteinuria 7.2 g/day, severe anemia, and active urinary sediment. Serologic workup demonstrated marked hypocomplementemia (C3 0.6 g/L, C4 <0.02 g/L) and elevated rheumatoid factor (117 IU/mL), while autoimmune testing (ANA, ANCA, dsDNA) and serum cryoglobulins were repeatedly negative. Further evaluation showed elevated high free light chain ratio (kappa/lambda 4.23 Ref:0.26_1.65) with elevated IgM levels, Serum protein electrophoresis demonstrated a faint paraprotein band with negative serum immunofixation. Kidney biopsy showed a membranoproliferative pattern with diffuse endocapillary hypercellularity, double contours, and characteristic hyaline thrombi. Immunofluorescence showed granular capillary and mesangial staining for IgG, IgM, C3, C1q, and striking Kappa restriction, consistent with cryoglobulinemic GN. Bone marrow evaluation identified small clonal plasma cell population (0.08% by flow cytometry) with kappa restriction, establishing the diagnosis of MGRS. The patient was initiated on clone-directed therapy with Daratumumab, Cyclophosphamide, Bortezomib, and Dexamethasone (Dara-CyBorD). By month six, she achieved complete hematologic response and dramatic renal recovery.

Discussion

This case highlights renal-limited seronegative CryoGN as an important manifestation of MGRS. Negative serum cryoglobulins do not exclude the diagnosis, particularly in the presence of hypocomplementemia and elevated rheumatoid factor. Kidney biopsy is the gold standard for the diagnosis, even low burden plasma cell clone (<1%) can produce nephrotoxic monoclonal proteins leading to devastating renal failure. This case demonstrates that rapid, clone-directed therapy with Daratumumab-based regimens can effectively eradicate the pathogenic clone and reverse severe renal injury.