Non-crystalline light chain proximal tubulopathy, a morphologically protean entity

Abstract

Background Light chain proximal tubulopathy (LCPT) is a rare form of paraprotein-related disease, occurring in two main histopathological forms; crystalline and non-crystalline. The clinicopathological features, treatment strategies and outcomes, especially of the non-crystalline form, are not well described. Methods Single-centre retrospective case series of 12 LCPT patients, 5 crystalline and 7 non-crystalline, between 2005-2021. Observations Median age was 69.5 years (range, 47-80). 10 patients presented with CKD and significant proteinuria (median eGFR of 43.5 ml/min/1.73m2; uPCR 328 mg/mmol). Only 6 patients had known haematological disease at the time of renal biopsy. Multiple myeloma (MM) was diagnosed in 7 cases and MGRS in 5. A clone was detected in all cases combining serum/urine electrophoresis and free LC assays. Crystalline and non-crystalline variants had similar clinical presentations. For the non-crystalline variant, a diagnosis was reached based on combination of CKD without other cause, haematological work-up, LC restriction on IF and abnormalities on EM. Nine of 12 patients received clone-directed treatment. Patients who achieved haematological response (including all non-crystalline LCPT) had improved renal outcomes over a median follow-up of 79 months. Conclusions The non-crystalline variant may go unrecognised because of its subtle histopathological features and requires EM to distinguish it from “excessive LC resorption without tubular injury”. Clone-directed treatment with good haematological response improves renal outcomes in both variants but limited data exist in MGRS. Multi-centre prospective studies are needed to better define the clinico-pathological characteristics associated with poor outcomes and optimize treatment strategies in patients with MGRS.

Light-chain proximal tubulopathy: a retrospective study from a single Chinese nephrology referral center

“…Complete or partial FS may occur on LCPT patients. In this study, 10% of the patients (2/19) exhibited FS, and they were all crystalline LCPT patients, which was relatively lower than reported series before [ 14 ]. This indicates that the FS-inducing mechanism may be independent of the crystal-forming process.…”

Nonalbumin Proteinuria in a Patient with Slowly Worsening Kidney Function

“…In addition to MM and monoclonal gammopathy of renal significance, LCPT has also been reported in association with chronic lymphocytic leukemia, lymphoma, and Waldenstrom macroglobulinemia. 4,5 The clinical presentation of LCPT can be heterogenous with variable degree of proteinuria (subnephrotic or nephrotic range), adult onset of Fanconi syndrome (in a subset of patients), and different stages of CKD. Treatment is directed at the underlying clone, and renal remission depends heavily on hematological remission which may be achieved by stem cell transplantation after chemotherapy in select patients.…”

“…Overall, patients who respond well to treatment are likely to have a favorable renal prognosis as well. 4,5 Teaching Points c LCPT can uncommonly be a presenting manifestation of MM. c Deposition of light chains in proximal tubular cells can lead to crystalline or noncrystalline inclusions seen in lysosomes on electron microscopy.…”

“…In addition to MM and monoclonal gammopathy of renal significance, LCPT has also been reported in association with chronic lymphocytic leukemia, lymphoma, and Waldenstrom macroglobulinemia. 4 , 5 …”

“…Overall, patients who respond well to treatment are likely to have a favorable renal prognosis as well. 4 , 5 …”