NDT Advance Access published online on October 19, 2007
Nephrology Dialysis Transplantation, doi:10.1093/ndt/gfm684
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Renal involvement in systemic amyloidosis*
An Italian collaborative study on survival and renal outcome
1 Renal Unit, Azienda Ospedaliero-Universitaria Careggi, Firenze, Italy 2 Renal Unit, Nuovo Ospedale S. Giovanni di Dio, Firenze, Italy 3 Renal Unit, Ospedale Mauriziano Umberto I°, Torino, Italy 4 Amyloid Centre, Ospedale Universitario S. Matteo, Pavia, Italy 5 Renal Unit, Ospedale S. Maria delle Croci, Ravenna, Italy 6 Renal Unit, Ospedale R. Silvestrini, Perugia, Italy 7 Renal Unit, Ospedali Riuniti, Foggia, Italy 8 Dialysis Centre "Ulivella", Istituto Fiorentino di Cura e Assistenza, Firenze, Italy
Correspondence and offprint requests to: Correspondence and offprint requests to: Franco Bergesio, MD, Renal Unit-Azienda Ospedaliero-Universitaria Careggi, Villa Monna Tessa, Viale Pieraccini 18, 50139 Firenze, Italy. Tel: +39-055-7949-212/ +39-055-7949-278; E-mail: francobergesio{at}libero.it
 |
Abstract |
|---|
 Top Abstract IntroductionPatients and methodsResultsDiscussionConcluding remarksAppendix List of participating...References |
|---|
Background. Few data are available from large population-based studies on survival and renal outcome of patients with renal involvement and different types of systemic amyloidosis.
Methods. Two hundred and ninety of over 373 patients affected from systemic amyloidosis with renal involvement diagnosed in Italy between January 1995 and December 2000 were followed from diagnosis to death or until the last available clinical control. Eighty-three patients were excluded from analysis either because the amyloid type remained undetermined or they were lost at follow-up. Clinical and laboratory information was collected according to the different types of amyloidosis using a specific form which included renal function with 24 h proteinuria at diagnosis and at the end of follow-up, the type and the date of onset of dialysis and the kind of treatment they underwent.
Results. The median time of follow-up was 24 months in primary (AL) amyloidosis (range: 1–88 months), 16 months in AL with associated multiple myeloma (MM + AL: range 1–76 months), 30 months in reactive (AA) amyloidosis (range: 1–99 months) and 52 months in patients with familial forms (AF: range 14–82 months). Patients with AL showed a significantly shorter survival than AA. Despite no significant differences of renal outcome or survival on dialysis being observed between the two groups, a lower renal survival with a higher number of patients who progressed to end-stage renal disease (ESRD) was observed in patients with AA. Overall survival was markedly improved in patients with AL who underwent a specific therapy (conventional chemotherapy or autologous stem cell transplantation (ASCT)) even in the absence of a positive kidney response. Multivariate analysis showed cardiac involvement and specific therapy to significantly influence survival in AL whereas age, serum creatinine (sCr) and heart involvement significantly affected survival in AA. In both groups, sCr and heart involvement were the most relevant predictors for renal outcome, together with urinary protein excretion, in patients with AA.
Conclusions. Our results show a worse survival in AL due to the higher prevalence of heart involvement in this group and emphasize that a specific therapy significantly prolongs survival and slows the progression of renal disease in patients with AL. We suggest that a late nephrological referral is likely the cause of the higher sCr found at presentation in patients with AA and probably accounts for the lower renal survival observed in the short term in these patients. At the time being, renal transplantation and ASCT are still rare therapeutic options for renal patients affected from systemic amyloidosis.
Keywords: AA amyloidosis; AL amyloidosis; renal amyloidosis; renal outcome; survival
|
Introduction |
|---|
|
TopAbstractIntroductionPatients and methodsResultsDiscussionConcluding remarksAppendix List of participating...References |
|---|
Renal involvement is quite common in systemic amyloidosis of any type [1]: AL (primary or immunoglobulin light chain associated) [2–4], AA (secondary or reactive to chronic inflammation) [5,6] or AF (heredofamilial) [7]. However, data on survival and renal outcome of patients with renal amyloidosis are usually limited to patients either with AL or AA type [2,6,8]. Unfortunately, no epidemiological data are available from a large cohort of patients suffering from different types of systemic amyloidosis and renal involvement.
In addition, dated and scarce is the information concerning the incidence and prevalence of AL and AA amyloidosis among the causes ofend-stage renal disease (ESRD). Indeed, in 1989 the combined report on regular dialysis and transplantation in Europe reported that amyloidosis was responsible for 1.6% of all patients with ESRD starting dialysis in that year and that three quarters of these patients suffered from AA due to chronic inflammatory diseases, among which rheumatoid arthritis was the most prevalent [9]. Although the frequency of the disease in the different European registries of renal biopsies is well known [10,11], since then no data have ever been published about the relative frequency of AA and AL with the exception of our recent report which showed a clear prevalence of AL [12].
At that time, however, the characterization of amyloid deposits was essentially based on major clinical and laboratory criteria such as a history of long-standing inflammatory process or the presence of a monoclonal component (MC), either in serum or urine, while the screening for heredofamilial forms had not yet been introduced into clinical practice [13].
In regard to AL, survival has greatly improved from the 13.2 months described by Kyle et al. in 474 patients from the Mayo Clinic in 1995 [3] to 46 months reported by Palladini et al. in 645 patients followed at Pavia Amyloid Centre in 2003 [4]. In both studies, renal involvement occurred in about two-thirds of the overall population examined with 18% of patients reported by Palladini et al. who progressed to ESRD and dialysis after a median time of only 7.5 months [8].
Survival was markedly influenced in both series by heart involvement [3,4].
Few studies addressed survival of patients with AA amyloidosis. Gertz et al. described a median survival of 24 months in 1991 [5], Joss et al. reported an almost doubled figure in 2000 [6] and Lachman et al. recently reported as much as 10 years median survival in a large cohort of patients in the UK [14]. None of these studies described a significant heart involvement. To date, only two papers have described the clinical course and outcome of patients with systemic amyloidosis on dialysis [15,16].
Diagnostic approach and treatment has greatly improved in the past years both for AL and for underlying diseases responsible for AA providing new opportunities to improve survival and renal outcome. In particular, autologous stem cell transplantation (ASCT) has become more common for patients with AL as well as renal or heart transplantation in cases with severe organ failure [2,17]. However, no one knows the current policy of different nephrological or internal medicine centres towards these emerging treatments as well as the results in terms of either renal or haematologic response. For this reason, we have set up a retrospective survey throughout Italy on survival and renal outcome of patients with different types of systemic amyloidosis and renal involvement.
|
Patients and methods |
|---|
|
TopAbstractIntroductionPatients and methodsResultsDiscussionConcluding remarksAppendix List of participating...References |
|---|
The clinical and laboratory records of 373 patients with biopsy-proven systemic amyloidosis with renal involvement diagnosed in Italy between January 1995 and December 2000 were retrospectively reviewed for follow-up analysis.
Patients were collected from 45 major renal units representing 35% of all nephrological centres associated to the Italian Society of Nephrology (SIN) and from three internal medicine and one haematology units associated to the Italian Society of Amyloidosis (SIA) (see the appendix).
All patients had evidence of amyloid deposits on renal biopsy or, according to criteria for non-invasive diagnosis of amyloidosis [18], at an alternate site such as abdominal fat tissue (AFT), provided they showed typical signs of renal involvement (UPE > 0.5 g/day and/or renal insufficiency) and did not have diabetic nephropathy. Amyloid cardiomiopathy was diagnosed when typical features of diastolic dysfunction, granular sparkling of myocardial texture and increased interventricular septum thickness on echocardiography occurred in the absence of other potential causes of left ventricular hypertrophy. Detailed characteristics of the population have been reported elsewhere [12].
Inclusion criteria
All patients with the characterization of amyloid deposits and at least one clinical control after diagnosis were included in the study.
Eighty-three out of 373 patients (22% of the overall population) were excluded from analysis at follow-up either because the type of amyloidosis remained undetermined (n = 26) or because they were lost at follow-up (n = 57). Of these, 39 were AL 5 with an associated multiple myeloma (AL + MM) and 18 were AA. Two hundred and ninety patients were finally selected for follow-up analysis: 167 (57%) were affected from AL, 31 (11%) from AL + MM, 86 (30%) from AA and 6 (2%) from AF. Characteristics of the selected patients are reported in Table 1.
|
Data collection
Follow-up ranged from diagnosis to death or until the last available clinical control.
Data were collected from December 2001 to December 2003 and included the date of last clinical control and eventual of death with the relative serum creatinine (sCr) and UPE, cause of death, date of onset and type of dialysis and therapy options including ASCT and kidney transplantation. Therapy of patients affected from AL was carefully recorded according to whether they received only a supportive or a specific therapy. Specific therapy included conventional chemotherapy used for an adequate period of time (at least 6 months) or ASCT. Consequently, AL patients who underwent a specific therapy were arbitrarily considered to have fulfilled minimum criteria for potentially effective therapy (treated group) regardless of the type of conventional therapy they actually followed and were compared to patients who either did not follow any specific treatment or followed it inadequately (untreated group).
Because of the many different therapeutic schedules used in patients with AA and the poor drug information available, it was impossible to analyse the results in this group of patients. All patients underwent a supportive therapy for both renal insufficiency and/or nephrotic syndrome.
Cardiac involvement was present in 56 patients with AL (33%) and in 12 with AA (14%). Nine patients, 5 AL and 4 AA, had more than two organs involved.
Survival and renal outcome were calculated separately for AL, AL + MM and AA.
The cause of death was systematically investigated and registered in order to differentiate the conditions directly or indirectly related to the disease from those certainly unrelated. Deaths were recorded as ‘unknown’ whenever the cause was not reported.
Statistics
All data are presented as medians with range. Differences between groups were evaluated using Mann–Whitney U-test for unpaired data or 
2 analysis when necessary. Linear regression analysis was used to evaluate the rate of decline of renal function (1/sCr) versus time. Survival curves were derived from the Kaplan–Meier method using the Cox regression analysis to determine the variables affecting survival and log-rank test to evaluate the differences between the curves. A P < 0.05 was considered significant.
|
Results |
|---|
|
TopAbstractIntroductionPatients and methodsResultsDiscussionConcluding remarksAppendix List of participating...References |
|---|
Patient survival
The overall median time of observation was 25 months (range: 1–99 months) with 24 months for AL (range: 1–88 months), 16 months (range: 1–76 months) for AL + MM, 30 months for AA (range: 1–99 months) and 52 months for AF (range: 14–82 months).
AA had a significantly longer follow-up as compared to AL (30 months versus 24, P < 0.01).
AL showed a median age of 65 years (range: 34–87 years) with a slight prevalence of male gender while AA showed a similar age but with a prevalence of females (Table 1).
At the end of follow-up, 140 patients (48% of the entire population) were dead. Among these, 87 were AL (62%), 18 (13%) had MM + AL and 34 were AA (24%). Among the AF, only one patient died and for a cause unrelated to the disease. One hundred and fifty patients were still alive at the end of follow-up: 80 were AL (53%), 52 (35%) AA, 13 (9%) MM + AL and 5 (3%) AF.
The causes of death are reported in Table 2. Thirty-four deaths remained unknown and 17 were certainly not referable to amyloidosis. The remaining deaths are reported in detail and were ascribed directly or indirectly to amyloidosis.
|
Median survival was significantly longer in AA (79 months) than in patients with AL (37 months, P = 0.008) (Figure 1) with a cumulative survival at 2 years of 74% in AA and 65% in AL. Approximately 51% of patients with AA and 36% of patients with AL were still alive after 5 years. In both groups, survival was dramatically shorter in the case of heart involvement: 21 versus 57 months in AL and 21 versus 79 months in AA (Figure 2).
|
|
Patients with an associated MM showed a shorter (28 months), although not significant, median survival than AL.
Analysis of factors influencing survival in the overall population of patients showed that the different types of amyloidosis, age, heart involvement and sCr significantly affected survival. However, when the above factors were examined using a Cox regression model, the role of the different types of amyloidosis was no longer evident and only age, sCr and heart involvement remained significantly correlated to patient survival (Table 3). When multivariate analysis was carried out in AL, only heart involvement (HR 2.78, P = 0.000) and specific therapy (HR 0.40, P < 0.02) were found to significantly affect survival (Table 3). The strong influence of specific therapy on survival is clearly demonstrated by the corresponding survival curve (Figure 5, top). The kappa/lambda ratio (data not reported) did not influence the survival as well as age and sCr despite both of them showing a significant influence when examined alone. Multivariate analysis in AA showed age (HR 1.05, P = 0.002) and heart involvement (HR 3.4, P = 0.002) and sCr (HR 1.27, P = 0.001) as major predictors of poor survival in these patients (Table 3). Gender and UPE did not show a significant influence in both groups.
|
|
Renal outcome
Renal outcome was calculated using the time interval between diagnosis and the beginning of dialysis (kidney death). All patients who died before reaching ESRD were regularly ‘censored’.
Renal survival curves in both AL and AA are shown in Figure 3. Despite a shorter median survival in AA (33 versus 45 months) no significant differences were observed between the two curves, which, in the long run, tended to overlap and even to show a better trend in AA. By the end of the study, patients with an associated MM did not reach a median value thus showing a better renal outcome than AL (data not reported).
|
Patients with AL showed a slightly faster, although not significant, decline of renal function than patients with AA (Figure 4).
|
When the Cox regression analysis was applied to the factors potentially affecting renal outcome in AL such as age, gender, heart involvement, sCr, UPE, kappa/lambda ratio and specific therapy, only sCr showed to be a strong predictor of renal failure (HR 1.47, P = 0.000) while therapy and type of MC lost the influence found at univariate analysis (Table 4).
|
When the same analysis was performed in AA, sCr (HR 1.8, P = 0.000), UPE (HR 1.1, P = 0.001) and heart involvement (HR 2.8, P = 0.02) were found to significantly influence the renal outcome (Table 4).
Fifty-nine out of 152 patients with AL (39%) developed ESRD and started a dialysis programme. Of these, 51 entered a regular treatment on haemodialysis (HD) while 8 started a programme on peritoneal dialysis (PD). Correspondingly, 37 patients out of 78 with AA (47%) developed ESRD and had to begin a dialytic therapy: 33 on HD and 4 on PD. Noteworthy, a few patients were already on dialysis at the time of diagnosis (5 in AL and 4 in AA).
Patients with AA showed a significantly higher sCr (Table 1) at diagnosis than patients with AL and starting earlier the dialitic therapy (Figure 3).
In both groups, patients who developed ESRD showed a significantly higher sCr at presentation with no differences concerning UPE and in AL kappa/lambda ratio (Table 5).
|
Concerning renal outcome in AF, three patients showed a progression of renal disease, one of whom had to start peritoneal dialysis, and three did not show any significant changes.
When death or dialysis were considered as clinical endpoints, age, sCr and heart involvement were the major predictors of a poor outcome (Table 6).
|
Response to treatment
Seventy patients out of 167 fulfilled criteria for specific therapy.
AL patients who underwent a specific therapy (‘treated patients’) showed a marked improvement of both overall and renal survival (Figure 5) despite a poor kidney response.
When the analysis was adjusted for other variables, therapy was found to significantly affect only overall survival. Renal response was considered improved whenever a 50% decrease in UPE occurred in the absence of a 25% increase of sCr concentration [18].
According to the above-mentioned criteria only 10 out of 70 patients who were treated improved (‘14% of responders’) as opposed to 47 who showed a disease progression and to 13 who did not show any significant changes (‘not responders’). In as many as 64 patients there was no evidence of a specific therapeutic intervention (‘untreated patients’).
Among specific therapy, 19 patients, including one with MM, underwent ASCT, 33 followed a conventional alkylating-based regimen of melphalan plus prednisone, 10 followed melphalan plus high-dose dexamethasone, 3 underwent VAD regimen (vincristine, adriamycin and dexamethasone) and 5 followed various combinations of chemotherapic agents including thalidomide in 3 patients and iododoxorubicin in 2.
Kidney response after ASCT was slightly better than that observed after conventional chemotherapy. Four patients improved, 4 did not show significant changes and as many as 11 showed disease progression, 6 of whom starting a regular dialysis treatment. The median time of survival after ASCT was 28 months and 6 out of 19 patients died. One AL patient underwent renal transplantation and was referred with a still functioning graft 47 months after transplantation.
Dialysis
Median survival on dialysis was 11 months in AL and 17 in AA but the difference was not significant. In consideration of the low number of PD as compared to HD patients (12 versus 84), we could not compare the survival analysis of the two groups which, however, showed the same median time of survival of 6.5 months. As a consequence, we compared AL patients on dialysis (HD + PD) with the corresponding group of AA (HD + PD). Although we did not find significant differences, cumulative survival at 12 months was 48% for AL compared to 75% for AA. After 5 years, survival dropped to 18% in AL and 12% in AA (Figure 6). Mortality rate was 77% in PD and 63% in HD, with only two deaths occurring in the first month after the beginning of dialysis. Dialysis significantly affected survival in AA but not in AL patients (P = 0.0005, data not reported).
|
The mortality rate on dialysis showed an estimated 67% for AA and 63% for AL. Heart disease was the major cause of death in both groups regardless of the type of treatment they followed (PD or HD).
|
Discussion |
|---|
|
TopAbstractIntroductionPatients and methodsResultsDiscussionConcluding remarksAppendix List of participating...References |
|---|
Our results show a longer survival in patients affected from AA as compared to AL amyloidosis with no significant differences according to renal outcome.
To date, no studies have been reported which compared in the same cohort patients affected from AL and AA amyloidosis with the exception of a recent work by Cazalets et al. who reported a longer survival in AL as compared to AA [22].
AL amyloidosis
Kyle et al. studying 474 patients with AL reported a median survival of 13.2 months with half of them presenting with renal failure at diagnosis [3]. Unfortunately, no data are reported about renal outcome and survival on dialysis. The authors stated that elevated sCr at presentation had an adverse influence on survival in patients who lived at least 1 year after diagnosis. In a later study concerning 153 patients, the same authors found a median survival of 25.6 and 14.9 months respectively according to whether sCr at diagnosis was below or over 1.3 mg/dl. In contrast, survival was not correlated to UPE but rather to lambda light chain found in urine [20].
Data reported from the Italian Society for Amyloidosis showed in patients with AL either a 34- or 50-month survival according to whether or not they showed a "dominant" renal involvement [21].
In 2004 the same group reported, among 409 patients presenting with renal involvement, as many as 18% who progressed to ESRD after a median time of only 7.5 months.
Multivariate analysis showed younger age, UPE, sCr at diagnosis and haematologic response to treatment to independently affect the progression towards ESRD. Unfortunately, no data were reported on patient survival on dialysis [8].
In contrast to other reports [2,8,21,22], we did not find sCr at presentation to affect the overall survival in AL, and we were unable as well to confirm proteinuria as a predictive factor of renal outcome. In addition, we could not confirm that patients with a urinary lambda light chain had a lower survival. On the other hand, we confirmed the negative role played by heart involvement [2–4] and by an associated MM [25].
Despite our renal response, which was actually very poor (14% of responders) if compared to 49% of haematologic responders reported by Palladini et al. [8], our results confirmed the effectiveness of a specific therapeutic approach (either conventional or ASCT) as compared to supportive therapy in order to prolong survival and reduce the progression towards ESRD in keeping with previous studies which proved the beneficial use of alkylating agents [24,25].
Indeed, the use of alkylating agents may account for the improved survival and renal outcome of our patients on a specific therapy. It is feasible that, in the absence of a kidney response, this beneficial effect may depend on some haematologic response whose prevalence and entity however remains unknown. It is possible that the poor kidney response observed in our study may depend on a more advanced organ damage and/or on a poor selection of patients in particular of those who underwent ASCT.
Actually, functional improvement of the organs involved has been reported after the haematologic response but only in a portion of responsive patients [23].
Until recently, haematologic response could only be evaluated by few specialized laboratories and such information could not be available in large retrospective studies. In the last few years, however, a new assay for serum-free light chain analysis has allowed a safe and reliable method to detect and monitor the haematologic response [26].
Concerning renal transplant, older age, the presence of renal failure and/or of cardiac involvement have certainly reduced the opportunities for this choice in many of our patients.
AA amyloidosis
Survival appears greatly improved in our study as compared to 24.5 months reported by Gertz and Kyle [5] and to 52.9 months recorded by Joss et al. with only 18 months of renal survival [6]. Renal failure and a low serum albumin at diagnosis were the most important predictors for a poor outcome in these studies. In addition, Joss et al. also found UPE to have a significant influence on the progression of renal disease [6]. Recently, Torregrosa et al. reported in a group of patients without dialysis a survival of only 67% and 53% at 12 and 24 months, respectively [27]. Patients with AA seem to show a shorter renal survival with a higher number of patients who develop ESRD, in spite of an apparently slower decline of renal function. These differences however, are not significant and are largely dependent on the worse renal function found in these patients at the time of presentation, and in turn, a likely consequence of patients’ late referral [12].
Cardiac disease was the second cause of death in spite of a relatively low incidence of heart involvement (14%) compared to patients with AL or MM (37% and 51% respectively) [12,3,4].
Indeed, the heart is far more frequently involved in AL amyloidosis, amyloid cardiomiopathy being rarely extensive in AA and almost never resulting in heart failure [3,13].
Recently, Lachmann et al. [7] identified several abnormalities in 222 patients with AA amyloidosis who underwent echocardiography but only in two cases were they characteristic for amyloidosis.
Because of the retrospective character of our study and the different causes responsible for amyloidosis, the therapeutic regimens employed in the different centres were not comparable. In addition, pre- and post-treatment SAA concentrations, a basic marker of disease activity, were not available at the time of the study and could not be used to evaluate the response to treatment.
Gillmore et al. suggested that treatment in AA should be guided by frequent determinations of serum SAA concentrations which can usually provide invaluable prognostic information [28].
Dialysis
To date, only two studies have been published on patients with systemic amyloidosis on chronic dialysis. The first one, published by Moroni et al. in 1992 [15], concerned 43 patients with biopsy-proven renal amyloidosis of whom 27 affected from AA and 16 from AL, and the second one, published by Martinez-Vea et al. [16], concerned 48 patients of whom 11 were affected from AL and 37 from AA.
Both of them reported a prevalence of patients with AA with a median cumulative survival (AL + AA) of 25 and 52 months, much longer than that observed in our study either in AL or AA (11 and 17 months respectively). Younger age may account for the longer survival observed in their patients, another possible explanation also being the exclusion in both studies of patients who died within the first year and likely affected from a more severe disease. Conversely, Torregrosa et al. have recently reported in patients with AA a lower survival rate than that observed in our study (42% versus 75%) after 12 months of dialysis [27].
However, in agreement with our results, Moroni et al. did not find any difference in survival at any time during dialysis between patients with AL and with AA as well as between patients on haemo- or peritoneal dialysis [15].
|
Concluding remarks |
|---|
|
TopAbstractIntroductionPatients and methodsResultsDiscussionConcluding remarksAppendix List of participating...References |
|---|
Our results point to heart involvement and to treatment as the major factors affecting survival and renal outcome. The higher prevalence of heart involvement likely accounts for the shorter survival observed in AL. In contrast, the higher sCr at presentation found in AA can account for the differences observed in renal outcome between patients with AA and AL. These findings raise the problem of a late nephrological referral in AA and call for an improved cooperation between rheumatologists, internists and nephrologists. Our results emphasize in AL the protective influence on survival and renal outcome of a specific therapeutic approach and strengthen the need for an early diagnosis together with a wider and more careful application of current therapies including kidney transplantation and ASCT.
|
Appendix List of participating centres to the study |
|---|
|
TopAbstractIntroductionPatients and methodsResultsDiscussionConcluding remarksAppendix List of participating...References |
|---|
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
Acknowledgments |
|---|
We are grateful to Dr V. Boddi (Istituto di Igiene, Università di Firenze) and Dr L.F. Morrone (U.O. Nefrologia e Dialisi, Policlinico di Bari) for their support for statistical analysis and review of the manuscript. This study was supported in part by the Italian Society for Amyloidosis. Giovanni Palladini M was partly supported by an investigator fellowship by Collegio Ghislieri, Pavia, Italy.
Conflict of interest statement. None declared.
|
Notes |
|---|
* On behalf of the Immunopathology Group of the Italian Society of Nephrology.
|
References |
|---|
|
TopAbstractIntroductionPatients and methodsResultsDiscussionConcluding remarksAppendix List of participating...References |
|---|
- Falk RH, Comenzo RL, Skinner M. The systemic amyloidosis. N Engl J Med (1997) 337:898–909.
[Free Full Text] - Gertz MA, Lacy MQ. Dispensieri A. Immunoglobulin light chain amyloidosis and the kidney. Kidney Int (2002) 61:1–9.[Web of Science][Medline]
- Kyle RA, Gertz MA. Primary systemic amyloidosis: clinical and laboratory features in 474 cases. Semin. Hematol (1995) 32:45–59.[Web of Science][Medline]
- Palladini G, Perfetti V, Merlini GP. AL amyloidosis. Haematologica (2004) 89:30–36.
- Gertz MA, Kyle RA. Secondary systemic amyloidosis: response and survival in 64 patients. Medicine (1991) 70:246–256.[Medline]
- Joss N, McLaughlin K, Simpson K, et al. Presentation, survival and prognostic markers in AA amyloidosis. Q J Med (2000) 93:535–542.[Web of Science]
- Hawkins PN. Hereditary systemic amyloidosis with renal involvement. J Nephrol (2003) 16:443–488.[Web of Science][Medline]
- Palladini G. Organ survival in AL amyloidosis with renal involvement. In: ‘Amyloid and Amyloidosis’: 10th International Symposium on Amyloidosis—Grateau G, Kyle RA, Skinner M, et al, eds. (2004) Tours, France. 76–78.
- Tufveson G, Geerlings W, Brunner FP, et al. Combined report on regular dialysis transplantation in Europe, XIX, 1988. Nephrol Dial Transplant (1989) 4Suppl:45–29.
[Abstract/Free Full Text] - Schena FP, Pannarale G, Carbonara MC. Clinical and therapeutic aspects of renal amyloidosis. Nephrol Dial Transplant (1996) 11Suppl:963–68.
- Rivera FL, Lopez-Gomez JM, Peres-Garcia R. Spanish registry of glomerulonephritis. Frequency of renal pathology in Spain 1994–1999. Nephrol Dial Transplant (2002) 17:1594–1602.
[Abstract/Free Full Text] - Bergesio F, Ciciani AM. Santostefano M et al. Renal involvement in systemic amyloidosis. An Italian retrospective study on epidemiological and clinical data at diagnosis. Nephrol Dial Transplant (2007) 22:1608–1618.
[Abstract/Free Full Text] - Lachmann HJ, Booth DR, Booth SE, et al. Misdiagnosis of hereditary amyloidosis as AL (primary) amyloidosis. N Engl J Med (2002) 111:1786–1791.
- Lachmann HJ, Goodman HJB, Gallimore J. Characteristic and clinical outcome on 340 patients with systemic AA amyloidosis. In: Amyloid and Amyloidosis: 10th International Symposium on Amyloidosis—Grateau G, Kyle RA, Skinner M, et al, eds. (2004) Tours, France. 173–175.
- Moroni G, Banfi G, Montoli A, et al. Chronic dialysis in patients with systemic amyloidosis: the experience in Northern Italy. Clin Nephrol (1992) 38:81–85.[Web of Science][Medline]
- Martinez-Vea A, et al. End-stage renal disease in systemic amyloidosis: clinical course and outcome on dialysis. Am J Nephrol (1990) 10:283–289.[Web of Science][Medline]
- Dember LM. Emerging treatment approaches for the systemic amyloidosis. Kidney Int (2005) 68:1377–1390.[CrossRef][Web of Science][Medline]
- Gertz MA, Comenzo R, Falk RH, et al. Definition of organ involvement and treatment response in immunoglobulin light chain amyloidosis (AL): a consensus opinion from the 10th International Symposium on Amyloid and Amyloidosis. In: Am J Hematol. 79. 2005. 319–328.
- Garg AX, Papaioannou A, Ferko N, et al. Estimating the prevalence of renal insufficiency in seniors requiring long-term care. Kidney Int (2004) 65:649–653.[CrossRef][Web of Science][Medline]
- Gertz MA, Kyle RA. Prognostic value of urinary protein in primary systemic Amyloidosis (AL). Am J Clin Pathol (1990) 94:313–317.[Web of Science][Medline]
- Paladini G, Perfetti V, Obici L, et al. Coinvolgimento renale nell’amiloidosi AL: Sopravvivenza d’organo. In Abstracts of 43° "Congresso Nazionale della SIN". Firenze 22–25 Maggio, 2002. Giornale Italiano di Nefrologia (2002) 19:S2.
- Cazalets C, et al. Epidemiologic description of amyloidosis diagnosed in University Hospital of Rennes from 1995 to 2000. In: 10th International Symposium on Amyloidosis—Grateau G, Kyle RA, Skinner M, eds. (2004) Tours, France. 275–277.
- Palladini G, Perfetti V, Obici L, et al. Association of melphalan and high-dose dexamethasone is effective and well tolerated in patients with AL (primary) amyloidosis who are ineligible for stem cell transplantation. Blood (2004) 103:2936–2938.
[Abstract/Free Full Text] - Palladini G, Kyle RA, Larson D, et al. Multicentre versus single centre approach to rare disease: the model of systemic light chain amyloidosis.
- Montseny JJ, Kleinknecht D, Meyrier A, et al. Long-term outcome according to renal histological lesions in 118 patients with monoclonal gammopathies. Nephrol Dial Transplant (1998) 13:1438–1445.
[Abstract/Free Full Text] - Bradwell A, Carr-Smith HD, Mead GP, et al. Highly sensitive automated immunoassay forimmunoglobulin free light chains in serum and urine. Clin Chem (2001) 47:673–680.
[Abstract/Free Full Text] - Torregrosa E, Hernandez-Jaras J, Calvo C, et al. Secondary amyloidosis (AA) and renal disease. Nefrologia (2003) 23:321–6.[Web of Science][Medline]
- Gillmore JD, Lovat LB, Persey MR, et al. Amyloid load and clinical outcome in AA amyloidosis in relation to circulating concentration of serum amyloid A protein. Lancet (2001) 358:24–29.[CrossRef][Web of Science][Medline]
Revision received 17. 7.07. Accepted in revised form: 5. 9.07
CiteULike 
Connotea 
Del.icio.us What's this?
This article has been cited by other articles:
|
|
 |
|
  M. A. Gertz, N. Leung, M. Q. Lacy, A. Dispenzieri, S. R. Zeldenrust, S. R. Hayman, F. K. Buadi, D. Dingli, P. R. Greipp, S. K. Kumar, et al. Clinical outcome of immunoglobulin light chain amyloidosis affecting the kidney Nephrol. Dial. Transplant., October 1, 2009; 24(10): 3132 - 3137. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
P. Ronco and P. Aucouturier Renal involvement in AL amyloidosis: the facts, the promise and the hope Nephrol. Dial. Transplant., October 1, 2009; 24(10): 2967 - 2969. [Full Text] [PDF]
|
|
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||