الفهرس 
INTRODUCTIONOnly 14 pages are availabe for public view
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Abstract
Monoclonal gammopathies consist of a heterogeneous group of
disorders characterized by clonal proliferation of immunoglobulin
producing B-lymphocytes or plasma cell clone. In most patients, the
proliferating cells continue to secrete immunoglobulin, which can be
detected in the blood or the urine as a monoclonal immunoglobulin
[monoclonal (M) protein]. The M protein may consist of a heavy and
light chain, light chain only, or less commonly, heavy chain only.
There is a wide spectrum of monoclonal gammopathies, extending
from the premalignant process called monoclonal gammopathy of
undetermined significance (MGUS) to overt malignancy such as
multiple myeloma. Patients with monoclonal gammopathies may
develop symptoms not just because of malignant transformation, but
also because of idiosyncratic properties of the secreted M protein. Thus,
disorders such as AL amyloidosis (amyloid light-chain amyloidosis),
cryoglobulinemia, and cold-agglutinin disease may occur without the
need for malignant transformation, primarily because of the unique
disease-producing properties of the individual M protein. However,
some patients may have both: malignancy and paraprotein-related
manifestation. For example, approximately 10% of patients have both
AL amyloidosis and multiple myeloma.
Similarly, cryoglobulinemia can occur in patients with
immunoglobulin M (IgM) type of MGUS (premalignancy) or in patients
with overt Waldenstrom macroglobulinemia (malignancy).
The kidney may be affected by a variety of lesions in the setting of
a monoclonal gammopathy. Different examples of monoclonal
gammopathy associated renal lesions include: AL or heavy-chain
amyloidosis, proliferative glomerulonephritis with monoclonal
immunoglobulin deposits, immunotactoid glomerulopathy, light-chain
proximal tubulopathy, crystal storing histiocytosis, etc. In most cases,
the renal injury is secondary to the M protein secreted in the
premalignant MGUS stage (rather than the malignant stages of multiple
myeloma or Waldenstrom macroglobulinemia).
The term ‗monoclonal gammopathy of renal significance (MGRS)‘
has been introduced to indicate that although the patient has MGUS
(and not malignancy) the renal lesion is nevertheless a consequence of
the M protein, and thus has major implications for management and
prognosis. The term MGRS helps highlight patients who have renal
disease secondary to M protein secreted by a premalignant clone, but is
not a disease or diagnosis in itself. Monoclonal gammopathy-associated
renal diseases encompassed by the term MGRS are quite distinct in their
pathogenesis, kidney biopsy findings, clinical presentation, progression,
prognosis, and treatment.
In this review, we discussed the pathology and management of
specific monoclonal immunoglobulin (MIg) associated-renal lesions.
Most of these disorders are characterized by deposition of the MIg
(direct mechanism), whereas in a few cases the renal lesion is caused by
the MIg dysregulating the complement pathway (indirect mechanism).
In general, the treatment of monoclonal gammopathy-associated
renal lesions is directed at eliminating the underlying clonal plasma cell population to decrease or stop the production of the offending M
protein. This is done most effectively by using chemotherapy regimens
that have been developed for the treatment of multiple myeloma and AL
amyloidosis. Current treatment of MGRS is based on therapies targeting
the causal B-cell clone with treatment choices based on extrapolation of
treatments used for the equivalent overt malignancy. Therapeutic
choices should take into account the renal characteristics of the disease,
particularly the risk of CKD progression, the presence and severity of
extrarenal manifestations, and the safety profile of antineoplastic drugs
in renal impairment. Early diagnosis, when renal function is still
preserved, usually facilitates treatment management and results in better
long-term outcome. Because MGRS is a heterogeneous and relatively
rare entity, a common effort of both nephrologists and hematologists
inside well-designed prospective collaborative studies is required to
improve management.
In conclusion, MIg can cause a variety of renal diseases resulting
from the direct renal deposition of the MIg, and rarely from an indirect
mechanism via dysregulation of the alternative pathway of complement.
The monoclonal gammopathy-associated renal diseases are distinct in
their pathogenesis, kidney biopsy findings, clinical presentation,
progression, prognosis, and treatment. A thorough and complete
evaluation of the MIg-associated renal disease needs to be performed to
appropriately manage these patients.