Lambda Light-Chain Deposition Disease (LCDD) in the Setting of Presumed Diabetic Kidney Disease (DKD): A Diagnostic Challenge

Introduction: Differentiating DKD from LCDD can be a challenge due to similarities in clinical presentation and histologic appearance on light microscopy (LM). The most common light chain in LCDD is kappa (~80% patients). To illustrate the need for clinical awareness, we present a case of LCDD involving the rarer lambda light chain occurring in a patient with CKD presumed secondary to diabetes. Case Description: 67 year old male with hypertension and diabetes with a rapid drop in eGFR by 17 ml/min/m2 (creatinine rise from 1.6 to 2.3 mg/dL, GFR drop from 48 to 31 ml/min/m2) over 4 months. This prompted a secondary workup, revealing lambda light chain restriction on serum immunofixation. A kidney biopsy led to the diagnosis of lambda-LCDD. Multiple myeloma was subsequently diagnosed on bone marrow biopsy. Chemotherapy with daratumumab, lenalidomide, and bortezomib was initiated. Renal function stabilized. Discussion: LCDD is a rare monoclonal gammopathy of renal significance (MGRS) often leading to dialysis within ~ 4 years. It can resemble DKD clinically and histologically (on LM), however, immunofluorescence (IF) revealing monoclonality is crucial for differentiation, often alongside more pronounced systemic involvement in LCDD. In our patient, a rapid progression of his CKD provoked clinical suspicion, with lambda restriction on serum immunofixation leading to biopsy and diagnosis. Although LM showed mesangial expansion and basement membrane thickening similar to DKD, IF revealed lambda restriction, establishing the diagnosis of lambda-LCDD (Figure 1). In conclusion, atypical features of DKD should prompt suspicion for alternative diagnoses and possible kidney biopsy. Early diagnosis and treatment of LCDD is vital, as hematologic response improves renal survival, even in advanced disease.