 |
||||
| 2007 JASN IMPACT FACTOR 7.111 | HOME AUTHOR INFO EDITORIAL BOARD SUBSCRIBE FEEDBACK ALERTS HELP | |||
| CURRENT ISSUE | ARCHIVES | JASN Express | ONLINE SUBMISSION | |
|
||||
| 2007 JASN IMPACT FACTOR 7.111 | HOME AUTHOR INFO EDITORIAL BOARD SUBSCRIBE FEEDBACK ALERTS HELP | |||
| CURRENT ISSUE | ARCHIVES | JASN Express | ONLINE SUBMISSION | |
DISEASE OF THE MONTH |
*
Renal Division, INSERM Unit 489 and University Pierre et Marie Curie
(Paris 6), Hôpital Tenon (Assistance
Publique—Hôpitaux de Paris), Paris,
France.
INSERM Unit 25 and University René
Descartes (Paris 5), Hôpital Necker, Paris,
France.
Correspondence to Dr. Pierre Ronco, INSERM U 489, Hôpital Tenon, 4 rue de la Chine, 75020 Paris, France. Phone: 33-1-56-01-66-39; Fax: 33-1-56-01-69-99; E-mail: pierre.ronco{at}tnn.ap-hop-paris.fr
 |
Introduction |
|---|
 Top Introduction HistoryPathogenesisRenal PathologyClinical Features of LCDDDiagnostic InvestigationVariants of LCDD: LHCDD...Outcome and TreatmentReferences |
|---|
|
|
History |
|---|
|
TopIntroductionHistoryPathogenesisRenal PathologyClinical Features of LCDDDiagnostic InvestigationVariants of LCDD: LHCDD...Outcome and TreatmentReferences |
|---|
|
Pathogenesis |
|---|
|
TopIntroductionHistoryPathogenesisRenal PathologyClinical Features of LCDDDiagnostic InvestigationVariants of LCDD: LHCDD...Outcome and TreatmentReferences |
|---|
Ig Chain Structure
Ig are made up of two pairs of subunits: two HC and two LC, each of which
includes a variable domain implicated in antigen recognition, and a constant
region that itself includes one or several domains and that activates a
variety of effector systems. Binding to antigen and activating effector cells
or complement (i.e., antibody function) is made possible by the
association of two HC and two LC. LC may be of 
or 
type, with
one constant and one variable domain (termed CL and VL).
HC may be of nine isotypes (µ, 
1, 2, 3, 4,
1, 2, 
, and 
) that define Ig classes and
subclasses: IgM, IgG (including IgG1 to IgG4), IgA (including IgA1 and IgA2),
IgD, and IgE. HC include from the -NH2 to the -COOH terminus one
variable domain (VH) from a common repertoire for all isotypes and
three (for IgG, IgA, and IgD) or four (for IgM and IgE) constant domains,
termed CH1 to CH4 (see
Figure 1).
|
Normal Ig display a striking structural heterogeneity that is borne
essentially by the variable domains and is related to the diversity of the
antigenic determinants that they are supposed to recognize. These regions of
the Ig chains are encoded by numerous gene segments, the rearrangement of
which occurs during B-cell differentiation and is mandatory for Ig production.
Comparison of VH and VL sequences allowed definition of
variability subgroups on the basis of their homologies: HC express six
VH subgroups, chains express four V subgroups, and
chains express six V subgroups. The variability of
VH and VL is even higher in three small peptidic
portions called complementarity determining regions (CDR1, CDR2, and CDR3)
that form three loops at one end of the domain that constitutes the antibody
binding site.
At variance with normal polyclonal Ig, monoclonal Ig are secreted by a single clone of differentiated B cells that expands excessively, either in a tumoral context (myeloma, Waldenström's disease, etc.) or without patent hematologic malignancy (monoclonal gammopathy of undetermined significance). A monoclonal Ig may be secreted as free LC (or rarely, HC) that displays structural anomalies causing tissue deposition.
Abnormal Structures of LC Variable Domains
In LCDD, isotype restriction is significant; chains occur in
approximately 80% of cases. This contrasts with the increased to
ratio seen in amyloidosis. Data on N-terminal sequences of the LC from
six consecutive patients with LCDD suggested an overrepresentation of the rare
VIV variability subgroup
(10). This subgroup features a
longer CDR1 loop that contains some hydrophobic residues. The role of LC
variable region (VL) in LC deposition is suggested by the fact that
amino acid changes in VL were sufficient to promote tissue
deposition in mice that expressed a human LCDD VIV chain
(11).
The primary structures of a few additional LCDD precursors were analyzed at
the cDNA
(12,13)
and protein levels (14). As in
AL amyloidosis, no common structural motif emerged from these studies. The
most remarkable observations were unusual hydrophobic residues at positions
where they either could be exposed to the solvent or strongly modify the
conformation, especially in the CDR
(13,14).
In particular, molecular modeling experiments performed on
VI and VIV LC underline the presence of
leucine, isoleucine, or tyrosine at positions 27 and/or 31 in all known cases
of LCDD. Other nonpolar groups may be exposed on CDR regions, which suggests
that hydrophobic interactions are important either in the amorphous
precipitation of LC or in the mechanisms that lead to overproduction of ECM
components (15). Of note, in
contrast to LCDD LC, those involved in AL amyloidosis often present particular
acidic residues in CDR and might form fibrils through electrostatic
interactions.
When pathogenic LC could not be detected in the serum and urine, which occurred in 15 to 30% of patients, they seemed to be N-glycosylated in all tested cases (10,16). In vitro biosynthetic labeling experiments on short-term cultures showed that LC that were absent in the urine actually were secreted by the bone marrow plasma cells (1,17,18). Thus, together with the presence of hydrophobic residues, glycosylation might increase the LC propensity to precipitate in tissues and displace the equilibrium from soluble toward deposited amorphous forms.
Truncated HC
Twenty-two cases of HCDD have been reported
(19 and reviewed in reference
20). In all patients, a
monotypic HC without LC was detected in the deposits. A deletion of the
CH1 domain was found in the deposited or circulating HC in the 10
patients with HCDD where it was searched for. It also was suggested in
a patient with HCDD
(21). Deletions of the
CH1, hinge, and CH2 domains were found in one case
(8).
The loss of the CH1 domain suggests that secretion of the free,
abnormal HC is required for tissue deposition. Normal HC associate
posttranslationally with Ig binding protein (BIP) in the endoplasmic
reticulum. The LC later assemble with HC, and the complex is transferred to
the Golgi apparatus for further processing and secretion. Because the binding
site of BIP is located in the CH1 domain, when a mutant HC lacks
the CH1 domain, it fails to associate with BIP and thus may be
secreted as a free subunit in the circulation. However, CH1
deletion seems necessary but not sufficient for deposition, and it is likely
that the VH also contributes to tissue deposition, ultrastructural
aspects of the deposits, and ECM accumulation. Indeed, in HC disease, a
lymphoproliferative disorder with free HC secretion without corresponding
tissue deposition, the variable regions are found to be deleted partially or
entirely, together with the CH1 domain. In HCDD, the variable
regions are present without major structural alteration, although in the two
cases in which they were sequenced
(8,22),
they contained unusual amino acid substitutions that might change the
physicochemical properties (e.g., charge, hydrophobicity). In
addition, the structure of an HCDD HC
(8) was strikingly similar to
that reported in a case of amyloid HC amyloidosis
(23), from which it differed
essentially at the V domain level. It is worth noting that in most cases of
HCDD, the circulating HC is associated with a -type LC. This bias may
reflect a preferential association of the VH with
VL domains.
Deposition Does Not Mean Pathogenicity
The finding by Solomon et al.
(24) of unexpectedly frequent
(14 of 40) deposition of human monoclonal LC along basement membranes in a
mouse experimental model raises the question of the relationship between
tissue precipitation and pathogenic effects. Human LC that were found
deposited along basement membranes in mice were predominantly of the
type (9 of 14), contrasting with the striking predominance of chains
in MIDD (24). In addition, LC
deposition similar in aspect to LCDD by immunofluorescence but with no or only
scanty granular electron-dense deposits in the tubular basement membrane may
occur in the absence of glomerular lesions and tubular basement membrane
thickening
(19,25).
One patient (Aucouturier P, Droz D, personal data) had an important LC
secretion and typical basement membrane deposits by immunofluorescence in the
kidney, without histologic alteration, and with normal renal functions 2 yr
after kidney biopsy. Thus, the propensity of a given LC to form deposits does
not necessarily mean that it is pathogenic, and immunofluorescence staining
should not be considered a sufficient criterion for pathologic diagnosis of
MIDD. As shown by characteristic pathologic changes and experimental evidence,
MIDD lesions are associated with local fibrosis.
LC-Induced Mesangial Fibrosis
Results of an in vitro study
(26) suggest that pathogenic
Ig chains may stimulate mesangial cells to secrete ECM components through
growth factors, in particular transforming growth factor-ß (TGF-ß).
LC-induced overproduction of collagen IV, laminin, fibronectin, and tenascin
was shown to be maximal at 72 h of incubation with mesangial cells
(27). Accumulation may be
increased by a concomitant inhibition of collagenase IV, which also is
mediated by TGF-ß. None of these effects was found with amyloid LC
(27). One way to prevent the
LC-induced fibrosis is to study the detailed mechanism of putative
ligand-receptor interactions that may govern the ability of a given LC to
stimulate the ECM synthesis. Other possibilities are to prevent the secretion
of TGF-ß or to interfere with the TGF-ß signaling pathway.
|
Renal Pathology |
|---|
|
TopIntroductionHistoryPathogenesisRenal PathologyClinical Features of LCDDDiagnostic InvestigationVariants of LCDD: LHCDD...Outcome and TreatmentReferences |
|---|
|
Glomerular lesions are much more heterogeneous (28,29). Nodular glomerulosclerosis (NGS) is the most characteristic; it is found in 60 (30) to 100% (19) of patients with LCDD. Expansion of the mesangial ECM was observed in all cases of HCDD, with NGS in almost all of them. Mesangial nodules are composed of PAS-positive membrane-like material and often are accompanied by mild mesangial hypercellularity. The capillary loops stretch at the periphery of florid nodules and may undergo aneurysmal dilation. Bowman's capsule may contain a material that is identical to that present in the center of the nodules. These lesions resemble nodular diabetic glomerulosclerosis, but some characteristics are distinctive: the distribution of the nodules is fairly regular in a given glomerulus, the nodules are poorly argyrophilic, and exudative lesions as "fibrin caps" and extensive hyalinosis of the efferent arterioles are not observed. In occasional cases with prominent endocapillary cellularity and mesangial interposition, the glomerular features mimic lobular glomerulonephritis. Milder forms of LCDD simply show an increase in mesangial matrix and sometimes in mesangial cells and a modest thickening of the basement membranes that are abnormally bright and rigid. Glomerular lesions may not even be detected by light microscopy but require ultrastructural examination. These lesions may represent early stages of glomerular disease or be induced by LC with a weak pathogenic potential. Their diagnosis would be unrecognized without the immunostaining results. Arteries, arterioles, and peritubular capillaries all may contain PAS-positive deposits in close contact with their basement membranes (Figure 2B). Deposits do not show the staining characteristics of amyloid, but they may be associated with Congo red—positive amyloid deposits in approximately 10% of patients (19).
Immunofluorescence Microscopy
A key step in the diagnosis of the various forms of MIDD is
immunofluorescence examination of the kidney. All biopsy specimens show
evidence of monotypic LC (mostly ) and/or HC fixation along tubular
basement membranes. This criterion is requested for the diagnosis of MIDD.
The tubular deposits stain strongly and predominate along the loops of Henle and the distal tubules, but they also often are detected along the proximal tubules. In contrast, the pattern of glomerular immunofluorescence displays marked heterogeneity. In patients with NGS, deposits of monotypic Ig chains usually are found along the peripheral glomerular basement membranes and, to a lesser extent, in the nodules themselves. The staining in glomeruli typically is weaker than that observed along the tubular basement membranes. This may not be a function of the actual amount of deposited material, because several cases in which glomerular immunofluorescence was negative despite the presence of large amounts of granular glomerular deposits by electron microscopy have been reported (31). Local modifications of deposited LC thus might change their antigenicity (18). In patients without nodular lesion (Figure 3A), glomerular staining occurs mainly along the basement membrane, but it may involve the mesangium in some cases. A linear staining usually decorates Bowman's capsule. Deposits frequently are found in vascular walls and interstitium.
|
In patients with HCDD, immunofluorescence with anti-LC polyclonal and
monoclonal antibodies is negative despite typical NGS. Monotypic deposits of
, , or µ HC may be identified. All subclasses may be
observed. Analysis of the kidney biopsy with monoclonal antibodies specific
for the constant domains of the HC allowed identification of a
deletion of the CH1 domain in all tested cases. In most cases of
HCDD, except those with deposits of 4 that does not activate
complement, complement components could be demonstrated in a granular or
pseudolinear pattern.
The accessory proteins (serum amyloid P component, apolipoprotein E, and ubiquitin) that are associated with AL amyloidosis and other amyloidoses are not present in LCDD deposits.
The composition of glomerular matrix proteins has been examined comparatively in NGS associated with LCDD and diabetes mellitus (32). Nodules are made of normal ECM constituents (collagen type IV, laminin, fibronectin) that are produced in excess and stain weakly for the small proteoglycans, decorin and biglycan (33). In a series of 36 patients with LC-related renal diseases including AL amyloidosis, cast nephropathy, fibrillary glomerulopathy, and LCDD, TGF-ß was detected only in glomeruli of the 3 patients with LCDD and nodular glomerular lesions (34). In the control series, it was found essentially in nodular diabetic glomerulosclerosis, which may suggest that distinct initial insults to the glomerular mesangium may trigger similar fibrogenetic pathways.
Electron Microscopy
The most characteristic ultrastructural feature is the presence of finely
to coarsely granular electron-dense deposits along the outer (interstitial)
aspect of the tubular basement membranes. In the glomerulus, they predominate
in a subendothelial position along the glomerular basement membrane and are
located mainly along and in the lamina rara interna. They also can be found in
mesangial nodules, Bowman's capsule, and the wall of small arteries between
the myocytes. Nonamyloid fibrils have been reported in a few patients with
LCDD or HCDD.
Association with Myeloma Cast Nephropathy
The association of monoclonal LC deposits, mostly along renal tubule
membranes, with typical myeloma cast nephropathy is more frequent than
reported initially (see Figure 3, B and
C). It was found in 23 of 72 (32%) patients with nonamyloid
monoclonal LC deposits in a French series
(30) and in 11 of 34 (32%)
patients with MIDD in a recent North American study
(19). NGS is, however,
infrequent (<10%), and some ribbon-like tubular basement membranes are seen
in fewer than half of the patients
(30). In addition, one third
of the patients do not have granular-dense deposits by electron microscopy.
The lack of ECM accumulation in most of these patients who present with acute
renal failure in the setting of a true myeloma may be due to insufficient time
for the development of fibrosis or to a weaker sclerogenic effect of the LC,
if any. As discussed previously, the presence of LC deposits along the tubular
basement membrane is not sufficient to make a diagnosis of MIDD.
|
Clinical Features of LCDD |
|---|
|
TopIntroductionHistoryPathogenesisRenal PathologyClinical Features of LCDDDiagnostic InvestigationVariants of LCDD: LHCDD...Outcome and TreatmentReferences |
|---|
Renal Disease
Renal involvement is a constant feature of MIDD, and proteinuria (composed
mostly of albumin) and renal failure often dominate the clinical presentation.
In 23 to 53% of the patients, albuminuria is associated with nephrotic
syndrome. However, in approximately 25% of them, it is less than 1 g/d, and
these patients exhibit mainly a tubulointerstitial syndrome
(Figure 2A). Albuminuria is not
correlated with the existence of NGS, at least initially, and may occur in the
absence of significant glomerular lesions by light microscopy. Hematuria is
more frequent (29 to 67%) than one would expect for a nephropathy in which
cell proliferation usually is modest, with a few exceptions. The prevalence of
hypertension is variable but must be interpreted according to medical
history.
The high prevalence (>90%), early appearance, and severity of renal failure are other salient features of MIDD. In most cases, renal function declines rapidly, which is a main reason for referral.
Renal features of the 22 patients with HCDD basically are similar to those seen in LCDD and LHCDD (see below).
Extrarenal Manifestations
MIDD is a systemic disease, but visceral LC deposits may be totally
asymptomatic and found only at autopsy. Liver and cardiac involvements are the
most common (29).
Liver deposits were constant in patients whose liver was examined (38) (Figure 3C). They are discrete, confined to sinusoids and basement membranes of biliary ductules without associated parenchymal lesions, or massive with marked dilation and multiple ruptures of sinusoids resembling peliosis. Hepatomegaly with mild alterations of liver function tests are the most usual symptoms, but several patients develop hepatic insufficiency and portal hypertension, and some of them die of hepatic failure (29).
Cardiac manifestations have been noted in as many as 80% of the reported cases of LCDD, but they must be interpreted with caution because of other age-dependent potential causes of heart disease. Arrhythmias, conduction disturbances, and congestive heart failure are seen. Echocardiography and catheterization may reveal diastolic dysfunction and a reduction in myocardial compliance similar to that seen in cardiac amyloid. As in the kidney and the liver, immunofluorescence showed monotypic LC deposits in the vascular walls and perivascular areas of the heart in all autopsy cases (16).
Deposits also may occur along the nerve fibers and in the choroid plexus, as well as in the lymph nodes, bone marrow, spleen, pancreas, thyroid gland, submandibular glands, adrenal glands, gastrointestinal tract, abdominal vessels, lungs, and skin. They may be responsible for peripheral neuropathy (20% of the reported cases), gastrointestinal disturbances, pulmonary nodules, amyloid-like arthropathy, and sicca syndrome.
Hematologic Disease
The most common underlying disease in MIDD is myeloma, which accounts for
40 to 50% of pure MIDD
(1,19,35,36,37)
and >90% of LC deposits associated with myeloma cast nephropathy. MIDD and
AL amyloidosis are found at postmortem examination in 5 and 10% of myeloma
patients, respectively (39).
MIDD, like AL amyloidosis, often is the presenting disease that leads to the
discovery of myeloma at an early stage. In some patients who first presented
with "common" myeloma and with normal-sized monoclonal Ig without
kidney disease, LCDD occurred when the disease relapsed after chemotherapy,
together with Ig structural abnormalities
(7,16).
Because melphalan was shown to induce Ig gene mutations, the disease in these
patients might result from the emergence of a variant clone induced by the
alkylating agent. Apart from myeloma, MIDD may complicate
Waldenström's macroglobulinemia and chronic
lymphocytic leukemia in rare cases
(17). It often occurs in the
absence of a detectable malignant process, even after prolonged (>10 yr)
follow-up. In such "primary" forms, a monoclonal bone marrow
plasma cell population can be documented easily by immunofluorescence
examination.
|
Diagnostic Investigation |
|---|
|
TopIntroductionHistoryPathogenesisRenal PathologyClinical Features of LCDDDiagnostic InvestigationVariants of LCDD: LHCDD...Outcome and TreatmentReferences |
|---|
LC isotype. Because sensitive techniques, including
immunofixation, fail to identify a monoclonal Ig component in 15 to 30% of
patients, renal biopsy plays an essential role in the diagnosis of MIDD and of
the associated dysproteinemia.
The definitive diagnosis is made by the immunohistologic analysis of tissue
from an affected organ, in most cases the kidney, with the use of a panel of
Ig chain—specific antibodies, including anti- and anti-
LC antibodies to stain the noncongophilic deposits. When the biopsy stains for
a single HC isotype and does not stain for LC isotypes, the diagnosis of HCDD
should be suspected (see below).
The diagnosis of plasma cell dyscrasia relies on bone marrow aspiration and
bone marrow biopsy with cell morphologic evaluation and, if necessary,
immunophenotyping with anti- and anti- antisera to demonstrate
monoclonality. Diagnostic criteria for a multiple myeloma are present in no
more than 50% of the patients with LCDD.
|
Variants of LCDD: LHCDD and HCDD |
|---|
|
TopIntroductionHistoryPathogenesisRenal PathologyClinical Features of LCDDDiagnostic InvestigationVariants of LCDD: LHCDD...Outcome and TreatmentReferences |
|---|
The first patients with HCDD were reported in 1993
(8). Twenty-two cases have been
described so far (19 and
reviewed in reference 20). The
clinical and pathologic features of HCDD basically are the same as in LCDD,
although several differences can be noted. First, lesions of NGS are constant
in patients with HCDD, whereas only a faint staining of tubular basement
membranes was seen in some patients (Figure
3D). Second, extrarenal deposits are less frequent in these
patients than in those with LCDD. They have been reported in heart, in
synovial tissue, in skin, in striated muscles, in pancreas, around thyroid
follicles, and in Disse spaces of the liver
(8 and reviewed in reference
20). Third, signs of
complement activation with renal complement deposition are present in most
patients with 1 or 3 HCDD
(19).
In some patients with HCDD, a monoclonal component cannot be detected in
serum and urine (8). In other
patients, a monoclonal IgG1 can be found in serum, but no deletion is
found in the HC (9).
Identification of the nephritogenic deleted HC that circulates in low amounts
then requires serum fractionation followed by Western blotting
(9)
(Figure 4). This finding
suggests that serum fractionation also should be performed in patients with
LCDD in whom usual immunochemical methods have failed to detect a circulating
monoclonal component.
|
|
Outcome and Treatment |
|---|
|
TopIntroductionHistoryPathogenesisRenal PathologyClinical Features of LCDDDiagnostic InvestigationVariants of LCDD: LHCDD...Outcome and TreatmentReferences |
|---|
As in AL amyloidosis, treatment should be aimed at reducing Ig production. Chemotherapy is logical in patients with MIDD and myeloma. It is controversial in the absence of overt malignancy given the uncertain outcome of LCDD and the absence of reliable follow-up criteria, especially in patients without detectable M component. However, it has become general practice to treat patients with steroids plus melphalan or a cytotoxic agent, irrespective of the accompanying hematologic disease.
Whether appropriate treatment can result in sustained remission has long remained unclear. Clearance of the LC deposits has been demonstrated unequivocally in some patients after intensive chemotherapy with syngeneic bone marrow transplantation or blood stem cell autografting (41,42). Disapperance of nodular mesangial lesions and LC deposits also was reported after long-term chemotherapy (43). These observations are of paramount importance: they demonstrate that fibrotic nodular glomerular lesions are reversible, and they argue for intensive chemotherapy in patients with severe visceral involvement.
Kidney transplantation has been performed in a few patients with MIDD and end-stage renal failure. Recurrence of the disease usually is observed. Therefore, intensive chemotherapy should be performed before kidney transplantation.
In conclusion, MIDD is a rare systemic disease that is characterized by severe renal failure as a result of the deposition of a monotypic LC and/or HC of Ig. Glomerular lesions are so similar to diabetic nephropathy that MIDD may serve as a model for the understanding of this plague of the third millennium. MIDD indeed is the only sclerotic glomerular disease in which the offending molecule is defined perfectly. As in AL amyloidosis, controlled trials are required to define the best chemotherapy combination according to clinical presentation and severity of renal failure.
|
Acknowledgments |
|---|
|
Footnotes |
|---|
|
References |
|---|
|
TopIntroductionHistoryPathogenesisRenal PathologyClinical Features of LCDDDiagnostic InvestigationVariants of LCDD: LHCDD...Outcome and TreatmentReferences |
|---|
IV subgroup in light chain
deposition disease. Immunol Lett42
: 63-66,1994[Medline]
chain in myeloma with light chain deposition disease. Clin Exp
Immunol 87:122
-126, 1992[Medline]
1 subgroup (ISE) in light chain deposition disease. Clin
Exp Immunol 91:506
-509, 1993[Medline]
IV subgroup in the kidney and plasma cells in light chain
deposition disease. J Clin Invest87
: 2186-2190,1991
This article has been cited by other articles:
 |
|
 |
|
  E. C. Lorenz, M. A. Gertz, F. C. Fervenza, A. Dispenzieri, M. Q. Lacy, S. R. Hayman, D. A. Gastineau, and N. Leung Long-term outcome of autologous stem cell transplantation in light chain deposition disease Nephrol. Dial. Transplant., June 1, 2008; 23(6): 2052 - 2057. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D. J. Salant, V. Sanchorawala, and V. D. D'Agati A Case of Atypical Light Chain Deposition Disease--Diagnosis and Treatment Clin. J. Am. Soc. Nephrol., July 1, 2007; 2(4): 858 - 867. [Full Text] [PDF]
|
|
|
|
 |
|
 M. Colombat, V. Gounant, H. Mal, P. Callard, and B. Milleron Light chain deposition disease involving the airways: diagnosis by fibreoptic bronchoscopy Eur. Respir. J., May 1, 2007; 29(5): 1057 - 1060. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. Ramos, R. Poveda, J. Sarra, A. Domingo, L. Carreras, and J. M. Grinyo Renal involvement in non-malignant IgM gammopathy Nephrol. Dial. Transplant., February 1, 2007; 22(2): 627 - 630. [Full Text] [PDF]
|
|
|
|
 |
|
 K O Alsaad and A M Herzenberg Distinguishing diabetic nephropathy from other causes of glomerulosclerosis: an update J. Clin. Pathol., January 1, 2007; 60(1): 18 - 26. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
P. Ronco, E. Plaisier, B. Mougenot, and P. Aucouturier Immunoglobulin Light (Heavy)-Chain Deposition Disease: From Molecular Medicine to Pathophysiology-Driven Therapy Clin. J. Am. Soc. Nephrol., November 1, 2006; 1(6): 1342 - 1350. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. M. Korbet and M. M. Schwartz Multiple Myeloma J. Am. Soc. Nephrol., September 1, 2006; 17(9): 2533 - 2545. [Full Text] [PDF]
|
|
|
|
 |
|
 M. Colombat, M. Stern, O. Groussard, D. Droz, M. Brauner, D. Valeyre, H. Mal, C. Taille, I. Monnet, M. Fournier, et al. Pulmonary Cystic Disorder Related to Light Chain Deposition Disease Am. J. Respir. Crit. Care Med., April 1, 2006; 173(7): 777 - 780. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
B. Alchi, S. Nishi, S. Iguchi, M. Shimotori, M. Sakatsume, M. Ueno, I. Narita, K. Saito, K. Takahashi, and F. Gejyo Recurrent light and heavy chain deposition disease after renal transplantation Nephrol. Dial. Transplant., July 1, 2005; 20(7): 1487 - 1491. [Full Text] [PDF]
|
|
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
HOME
CURRENT ISSUE
ARCHIVES
JASN Express
ONLINE SUBMISSION
AUTHOR INFO
EDITORIAL BOARD SUBSCRIBE FEEDBACK ALERTS HELP |
