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Kidney Week

Abstract: SA-PO114

A Case of Focal Immune-Complex Membranoproliferative Glomerulonephritis (MPGN) in Low-Risk Chronic Lymphocytic Leukemia

Session Information

Category: Onconephrology

  • 1600 Onconephrology

Authors

  • Tan, Akira Francis Henghui, Singapore General Hospital, Singapore, Singapore
  • Ong, Shin Yeu, Singapore General Hospital, Singapore, Singapore
  • Loh, Alwin Hwai Liang, Singapore General Hospital, Singapore, Singapore
  • Choo Chon Jun, Jason, Singapore General Hospital, Singapore, Singapore
  • Tan, Hui Zhuan, Singapore General Hospital, Singapore, Singapore
Introduction

A broad spectrum of kidney diseases is associated with chronic lymphocytic leukemia (CLL). Optimal treatment of low-risk CLL with renal involvement (CLL-R) is unknown.

Case Description

A 48 year-old Chinese man with low-risk CLL presented with new-onset microhematuria and subnephrotic range proteinuria (uPCR 1.88g/g) for evaluation. Peak serum creatinine (sCr) was 115µmol/L (baseline 81µmol/L). Investigations were notable for low C3 (0.88g/L), C4 (<0.06g/L) and IgG-λ monoclonal gammopathy (2g/L). Autoimmune markers, virologies, and serum cryoglobulins were negative.

Kidney biopsy showed focal membranoproliferative (MPGN) pattern of injury. No TMA changes were seen. Immunofluorescence showed C3-dominant glomerular and mesangial staining (2+), and segmental IgM mesangial staining (1+). Segmental C4d staining was observed. No deposits were seen on electron microscopy (EM). Pronase digestion was not performed. Findings were most consistent with CLL-related immune-complex MPGN.

Venetoclax and Obinutuzumab (Ven-Obi) was commenced. Thrombocytopenia developed 2 days after the first obinutuzumab infusion, leading to gross hematuria and acute kidney injury (AKI) (sCr 161µmol/L). Tumour lysis syndrome was excluded. AKI resolved with conservative management. Interestingly, normalization of complements and proteinuria reduction (uPCR 0.38g/g) were observed within 2 weeks of treatment. Treatment is ongoing but remain uncomplicated.

Discussion

We report a case of focal MPGN with C3 dominance in a patient with low-risk CLL. Lack of antigen retrieval techniques precluded the search for masked deposits. Positive C4d staining, together with low C3 and C4, suggested an immune-complex, instead of an alternative pathway mediated process. The absence of deposits on EM was likely due to early focal disease.

Studies suggest that clone-directed therapies improve renal outcomes in dysproteinemic-related kidney disease, but the optimal regimen and timing of treatment in early/mild CLL-R is unknown. We demonstrated early renal response to Ven-Obi in our patient. No tumor lysis syndrome was observed during treatment, although thrombocytopenia, a rare adverse effect of Obinutuzumab, did occur together with AKI, the latter possibly due to tubular obstruction by red blood cells casts. Longer follow-up is needed to determine treatment efficacy of Ven-Obi in CLL-R.