Use of bortezomib in heavy-chain deposition disease: a report of 3 cases.

Heavy-chain deposition disease (HCDD) is a rare complication of plasma cell dyscrasia in which monoclonal heavy chains deposit in glomerular and tubular basement membranes of the kidney. Clinical and pathologic features of HCDD have been well described in case reports and series, but evidence supporting specific therapies is sparse. Historically, the disease has had a poor prognosis, intensifying the need to clarify optimal treatments. We describe 3 cases of HCDD with biopsy-proven glomerular involvement, severe nephrotic syndrome, and decline in kidney function that were treated successfully with bortezomib, a proteasome inhibitor. None of these patients had multiple myeloma. In all cases, bortezomib-based therapy resulted in sustained resolution of nephrotic syndrome and improvement in kidney function. All 3 patients developed peripheral neuropathy; otherwise, treatment was well tolerated. To our knowledge, this is the first description of the clinical effectiveness of bortezomib against HCDD.

Afectación renal en las gammapatías monoclonales benignas: ¿una entidad infradiagnosticada? / No disponible

La nefropatía de las gammapatías monoclonales es debida principalmente al depósito de cadenas ligeras. Aunque se presenta sobre todo en cuadros malignos, también se ha descrito en pacientes cuya gammapatía es considerada «benigna». Se describen las características clínicas e histológicas de 9 casos de nefropatía por depósitos de cadenas ligeras diagnosticadas en el contexto de una gammapatía monoclonal sin datos de malignidad. Tres hombres y seis mujeres con edad media de 59,2 ± 12. Todos los pacientes presentaban al diagnóstico proteinuria y grados variables de insuficiencia renal con creatinina sérica media de 315 ±187. Dos requirieron diálisis desde el inicio. La histología renal mostró patrón nodular en 4 casos, mesangiocapilar en 3, lesiones sólo tubulares en 1 y mesangial en otro. Los depósitos renales más frecuentes fueron los constituidos por cadenas kappa (67%). Los tratamientos aplicados fueron: Prednisona en monoterapia (tres casos) o asociada aquimioterapia (melfalan, clorambucil o ciclofosfamid). En dos casos se añadieron recambios plasmáticos o autotrasplante de médula ósea, respectivamente. Tras un seguimiento medio de 4,89 ± DE: 3,69 años observamos desaparición de la proteinuria en más del 50% de los pacientes y estabilización o mejoría de la función renal en 3. Dos deellos necesitaron terapia renal substitutiva desde el inicio y existió progresión del fallo renal hasta los requerimientos dialíticos en los cuatro restantes. En caso de gammapatía monoclonal, incluso de carácter benigno, debe buscarse una posible afectación renal. La comprobación del depósito renal de cadenas ligeras debe hacer plantearse un tratamiento precoz, ya que la evolución a la insuficiencia renal terminal es frecuente (AU)

Renal involvement is observed frequently in association with malignant gammopathies, mainly those related to light chain deposition, although has also been described in non-malignant monoclonal gammopathy. This study reports the clinicopathological findings and outcome in 9 patients with nephropaty secondary to monoclonal immunoglobulin deposit in absence of malignancy. They were three men and six women and they were 59.2± 12 years old. All patients presented proteinuria and different levels of renal insufficiency (mean creatin in = 315 ± 187 micromol/L) at the moment of diagnostic. Two patients required dialysis at the time of renal biopsy. The pathology studies revealed a nodular sclerosing glomerulopathy in four cases, mesangiocapilary glomerulonephritis in three cases, only tubular lesions in one and mesangial lesions in the other one. The treatment applied was: Prednisone alone (two cases), with chemotherapy associated (melfalan in two, clorambucil in one and ciclophosphamide in another one). One patient received plasmapheresis and mycophenolate and another patient undergone a bone marrow authotransplant associated to mycophenolate and prednisone. One of the two patients who required dialysis at the moment of presentation was not treated. After a follow-up of more than 4years (4.89 ± DE: 3.69) renal function improved or remained stable in three patients and proteinuria was dissapaired in more than 50% of patients. Four patients had a worsening of renal function and they required dialysis during the time of follow-up (in 2.4 years ± DE: 4.3). In any case malignitation was observed. Chemotherapy stabilized or improved renal function in 3 of nine patients (33%) with non-malignant monoclonal gammopathy Non-malignant monoclonal gammopathy could go unnoticed. Appearance of abnormalities in renal routine tests deserves more in-depth diagnostic procedures, including renal biopsy. Evolution to end stage renal disease could probably be avoided or reduced in severity with early detection and treatment of this entity (AU)

Mu-heavy chain disease: presentation as a benign monoclonal gammopathy.

mu-Heavy chain disease (HCD) is a rare monoclonal lymphoid disorder characterized by the failure to assemble a complete IgM immunoglobulin. The mu-heavy chains analyzed to date revealed absence of the variable region and a shortened constant domain. We report the first case of mu-HCD presenting as a benign monoclonal gammopathy. The literature on the 27 reported mu-HCD cases is reviewed, and important clinical and laboratory findings are discussed. The ages of the patients ranged from 15 to 80 years (median, 57.5 years). Twenty-two of 27 patients had an associated lymphoplasma cell proliferative disorder. A monoclonal spike on routine serum protein electrophoresis was found in only 8 of 19 patients. Fourteen of 22 patients had Bence Jones proteinuria, but mu-HCD protein was reported in the urine of only two patients. The survival ranged from less than 1 month to 11 years (median, 24 months).