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

Area of Science:

• Nephrology
• Hematology
• Pathology

Background:

• Light chain proximal tubulopathy (LCPT) is a rare paraprotein-related kidney disease with crystalline and non-crystalline forms.
• Clinicopathological features and outcomes, particularly for the non-crystalline variant, are not well-defined.

Purpose of the Study:

• To describe the clinicopathological features, treatment, and outcomes of LCPT patients.
• To investigate the differences and similarities between crystalline and non-crystalline LCPT variants.
• To evaluate the impact of clone-directed treatment on renal outcomes.

Main Methods:

• Retrospective case series of 12 LCPT patients (5 crystalline, 7 non-crystalline) from 2005-2021.
• Analysis of clinical presentation, renal function (eGFR, proteinuria), hematologic diagnoses (MM, MGRS), and diagnostic methods (electrophoresis, LC assays, EM).
• Evaluation of treatment strategies and patient outcomes over a median follow-up of 79 months.

Main Results:

• Patients presented with chronic kidney disease (CKD) and significant proteinuria; 7 had multiple myeloma (MM) and 5 had monoclonal gammopathy of renal significance (MGRS).
• A clone was detected in all cases; crystalline and non-crystalline variants showed similar clinical presentations.
• Nine patients received clone-directed treatment; those achieving hematologic response, including all non-crystalline LCPT, showed improved renal outcomes.

Conclusions:

• The non-crystalline LCPT variant may be overlooked due to subtle histopathological features, requiring electron microscopy (EM) for diagnosis.
• Clone-directed treatment leading to hematologic response improves renal outcomes in both LCPT variants.
• Multicenter prospective studies are needed to better define outcomes and optimize treatment for MGRS-associated LCPT.