Light chain deposition disease with low glomerular proteinuria and multiple myeloma: If you search you find.

Light Chain Deposition Disease (LCDD) with low proteinuria is rare and represents a diagnostic challenge. Only 14 patients with biopsy proven renal LCCD and low proteinuria have been, in fact, reported in a recent multicentre retrospective study, confirming that this form is likely underdiagnosed.

An immigrant 65 years old Moldovan male patient, was referred to our Nephrology Unit for CKD of unknown origin (creatinine 350 μmol/L, proteinuria 0.8 g/day, anaemia (Haemoglobin [Hb] 9 g/dL), hypocalcemia). At the admission, WBCs and platelets count, blood calcium and phosphorous were normal, Hb 9 g/dL, creatinine 358 μmol/L, proteinuria 0.85 g/day and gamma globulins were reduced (9%). ANA, ANCA and complement were negative, serum free light chains (sFLCs) increased (kappa 136 mg/L, lambda 30 mg/L), with high kappa/lambda ratio (4,53). Urinary monoclonal FLCs kappa (Bence Jones proteinuria) were present and serum immunoglobulins were slightly reduced. Renal biopsy showed, mesangial and arteriolar FLCs kappa and lambda positive deposits and Congo Red and Tioflavine negative deposits. Immunofluorescence was negative for IgG, IgM, IgA, C1q, C3 and fibrinogen. Glomerular, mesangial, glomerular basal membrane and perivascular FLCs kappa positive dense deposits allowed the diagnosis of LCDD (Figure 1).

FIGURE 1

One sclerotic glomerulus, 2 with PAS positive mesangial deposits and duplication of Bowman capsule in one. (A) Arterial thickening of the parietal wall of two arteries (arrows). No sign of inflammation. PAS staining ×20; (B) Artery with deposit of amorphous material, Masson trichrome staining ×40. Positivity for Lambda light chain antibody in glomerular deposits (C) ×40 and prevalence for Kappa light chain antibody (D) ×40. Congo red and Thioflavin‐T were negative (not shown)

Medullary osteobiopsy found 16% of clonal immunophenotype kappa plasma cells allowing the diagnosis of Multiple Myeloma (MM) with LCDD.

No osteolytic lesions were present at the CT scan and echocardiogram was normal.

Treatment with Bortezomib/Dexametasone (2.52 mg/40 mg) was able to induce after 25 days a remarkable reduction of sFLCs kappa, the urinary FLCs disappeared and after 3 months the treatment was interrupted. The patient was then found suitable for autologous bone marrow transplant.

Approximately 50% of patients with MM experiences acute kidney injury (AKI) or CKD and severe AKI requiring dialysis generally occurs in 1–3% of these patients with reports in up to 12%.

LCDD with low or no glomerular proteinuria has been reported only in 1% of all the renal biopsy proven diagnoses. Due to the CKD of unknown origin that our patient presented at the admission in our Unit, renal biopsy was performed allowing the diagnosis. In the absence of significant proteinuria, in fact, paraproteinemias are not, generally, fully studied.

This case confirms the need of an accurate diagnostic workup for monoclonal gammopathy, including the determination of FLCs. The need of renal biopsy in patients with CKD of unknown origin, even without significant proteinuria, becomes therefore crucial for LCCD diagnosis. Early recognition of MM and its complications is extremely important, given the positive renal outcome following the timely clone‐directed therapy in addition to the autologous stem cells' transplant.

CONFLICT OF INTEREST

The authors declare no conflict of interest.