Clinical features of anemia in membranous nephropathy patients: a Chinese cohort study.

BACKGROUND: Anemia is a common complication in patients with progressive chronic kidney disease. This cohort study evaluated the prevalence, clinical features and prognosis of membranous nephropathy (MN) with anemia. METHODS: We retrospectively analyzed a cohort of MN patients diagnosed using renal biopsy between February 2012 and February 2018. The clinical and pathological characteristics at baseline were recorded, and the outcomes (hemoglobin, proteinuria and renal function) during follow-ups were also evaluated. Univariate and multivariate logistic regression analyses were performed to identify the independent risk factors for anemia in MN patients. The MN patients were divided according to the therapeutic effect they experienced as follows: without-anemia, completely corrected anemia, standard anemia treatment and nonstandard anemia treatment groups. We compared the rate of complete remission of MN and renal end-point events among the four groups. RESULTS: The median age of 483 patients was 42.43 (26.59, 50.20) years at the time of MN diagnosis. The prevalence of anemia at baseline was 23.81%, and the cumulative prevalence was 50.72%. There were 133 cases of mild anemia, 103 cases of moderate anemia and 9 cases of severe anemia; in addition, there were 228 cases of normocytic anemia and 17 cases of microcytic hypochromic anemia. Multivariate logistic regression indicated that acute renal tubule injury >5% (OR = 1.634, 95% CI 1.034, 2.581; p = 0.035), total protein level (OR = 0.949, 95% CI 0.923, 0.975; p < 0.001), cholesterol level (OR = 0.833, 95% CI 0.749, 0.926, p = 0.001), hypokalemia (OR = 2.612, 95% CI 1.227, 5.560, p = 0.013) and hypophosphatemia (OR = 2.653, 95% CI 1.303, 5.403, p = 0.007) were independent risk factors for anemia in MN patients. The complete remission rate of MN patients without anemia was significantly higher than that of anemia patients who exhibited treatment failure. The incidence of renal endpoint events was different among the four groups. CONCLUSION: The anemia experienced by MN patients is mainly mild and moderate, normocytic anemia. The pathological features of acute renal tubular injury and clinical nutritional status are independent risk factors for anemia. There were differences in renal prognosis among anemia patients with different treatment outcomes.

Long-term follow-up of autologous peripheral blood hematopoietic stem cell transplantation for refractory lupus nephritis-a series study of 20 patients.

BACKGROUND: Autologous hematopoietic cell transplantation (ASCT) improves immunologic homeostasis in autoimmune diseases. ASCT-treated refractory lupus nephritis (LN) has been reported. Nevertheless, the long-term outcome of patients with refractory LN after ASCT remains unknown. This study reports the outcomes of 20 refractory lupus patients with 10-year of follow-up after receiving ASCT. METHODS: Twenty-two patients with LN refractory to immunosuppressive therapy were enrolled. Twenty patients were examined closely and two cases died within 100 days after ASCT. Hematopoietic cell mobilization with cyclophosphamide and granulocyte colony-stimulating factor (G-CSF) was followed by collection of CD34+ positively selected cells. The conditioning regimen consisted of intravenous cyclophosphamide, rabbit antithymocyte globulin, methylprednisolone, and G-CSF. All immunosuppressive therapies were discontinued at the start of mobilization and corticosteroids were tapered rapidly after ASCT. RESULTS: Data was collected from 22 patients with refractory LN treated by ASCT. 59% were female, duration of lupus before ASCT was 46 (33-71) months, and median duration of follow-up after ASCT was 89.5 (56-108) months. 20 long-term followed up patients had an average follow-up time of 92 months (63.25-109.5). Eighteen patients achieved complete remission, one patient reached partial remission, one patient without remission started peritoneal dialysis at month 12, and one patient received short-term renal replacement therapy before ASCT started hemodialysis at 84 months after transplantation. Nine patients relapsed 10 times during the follow-up, and three patients received rituximab. Two patients relapsed during pregnancy after complete response and the Apgar scores of infants were 9 and 10, respectively. All nine patients received glucocorticoids and immunosuppressive medication after relapse and responded again. The 10-year overall survival, 10-year disease-free survival rate, and 10-year renal survival were 100%, 35%, and 90%, respectively. The rate of relapse was 45%. Complications included hypocytosis, infection, B-type insulin resistance syndrome, and monoclonal immunoglobulinemia. CONCLUSION: This study suggests ASCT is effective and safety in treating refractory LN and is beneficial to improve their long-term outcomes.

A risk stratification for systemic immunoglobulin light-chain amyloidosis with renal involvement.

Renal involvement is found in about 70% of patients with systemic immunoglobulin light-chain (AL) amyloidosis. However, there is no risk stratification system specialized for renal AL concerning patients' survival. Galectin-3 (Gal-3) has been reported to portend poor prognosis in other renal diseases. We measured Gal-3 and several traditional risk biomarkers of AL in baseline samples from 253 consecutive patients diagnosed with renal AL. At baseline, Gal-3 [Hazard ratio (HR): 1·46; P = 0·033], high-sensitivity cardiac troponin T (hs-cTnT) (HR: 2·65; P < 0·001) and difference between involved and uninvolved free light chains (dFLC) (HR: 1·81; P = 0·001) were independent predictors of all-cause mortality. The cut-off points for Gal-3, hs-cTnT, and dFLC were 20·24 ng/ml, 0·026 ng/ml, and 75·89 mg/l, respectively. Patients were stratified into four stages by assigning a score of 1 for each of the three biomarkers above the cut-off point. The proportions of patients with disease stages 1, 2, 3 and 4 were 17·0%, 37·2%, 29·2% and 16·6%, and the median overall survival times from diagnosis were 100, 60, 29 and 15 months, respectively (P < 0·01). Higher level of Gal-3 is associated with increased risk for mortality, and the risk stratification based on Gal-3 is a reliable model for predicting mortality in AL amyloidosis with renal involvement.

Induction therapy with bortezomib and dexamethasone followed by autologous stem cell transplantation versus autologous stem cell transplantation alone in the treatment of renal AL amyloidosis: a randomized controlled trial.

BACKGROUND: Although the use of bortezomib alone and in combination with steroids has shown efficacy in AL amyloidosis, its role in combination with high-dose melphalan and autologous stem cell transplantation (HDM/SCT) is unknown. In this study, we evaluated bortezomib in combination with dexamethasone (BD) for induction chemotherapy prior to HDM/SCT. METHODS: This was a single-center, prospective, randomized controlled trial comparing induction therapy consisting of two BD cycles followed by HDM/SCT (BD + HDM/SCT) with HDM/SCT alone in the treatment of patients with newly diagnosed AL amyloidosis. The hematological and organ responses of the patients were assessed every three months post HDM/SCT. RESULTS: Fifty-six patients newly diagnosed with renal (100%), cardiac (57.1%), liver (7.1%), or nervous system (8.9%) AL amyloidosis were enrolled in this study; 28 patients were assigned to each arm. Two patients died within 100 days of HDM/SCT (3.6% treatment-related mortality). The overall hematologic response rates in the BD + HDM/SCT arm and HDM/SCT arm at three, six and twelve months were 78.5% versus 50%, 82.1% versus 53.5% and 85.7% versus 53.5%, respectively. In the BD + HDM/SCT arm, 15 (53.5%) patients achieved a hematologic response after BD and before HDM/SCT. An intention-to-treat analysis revealed a higher rate of complete remission in the BD + HDM/SCT arm at both 12 and 24 months (67.9% and 70%, respectively) than with the HDM/SCT-only therapy (35.7% and 35%, respectively, P = 0.03). After a median follow-up of 28 months, the survival rates at 24 months post-treatment start were 95.0% in the BD + HDM/SCT group and 69.4% in the HDM/SCT alone group (P = 0.03). CONCLUSIONS: Our preliminary data suggest that the outcome of treating AL amyloidosis with BD induction and HDM/SCT was superior to the outcome of the HDM/SCT treatment alone. TRIAL REGISTRATION: This trial has been registered at clinicaltrials.gov with the number NCT01998503.

Risk factors, treatments and outcomes of patients with light chain amyloidosis who relapse after autologous stem cell transplantation.

Relapse after ASCT is an important factor affecting the long-term prognosis of patients with AL amyloidosis. However, the risk factors of relapse are unknown and there are limited studies on treatment outcomes of these patients. We retrospectively reviewed 170 patients with AL amyloidosis who underwent ASCT between 2010 and 2021. Seventy-six patients confirmed as relapse and the median time from ASCT to relapse was 39 months. On multivariate analysis of variables before and after ASCT, lambda restricted, dFLC >30 mg/L pre ASCT, reduced dose melphalan and dFLC >10 mg/L at 6 months after ASCT were independent risk factors for relapse, and achieving CR after induction therapy and renal response after ASCT were protective factors. Most relapsed patients were treated with bortezomib-based regimens (50%) followed by daratumumab-based regimens (22.2%) and other chemotherapy regimens (13.9%). The overall hematological response in evaluable patients was 68.2% with 56.8% achieving CR/VGPR. The median PFS and OS from post-transplant relapse were 25 months and 81 months, respectively. Patients receiving bortezomib or daratumumab showed a better survival compared to other chemotherapy regimens. In conclusion, this study identified independent risk factors of post-transplant relapse and demonstrated the superiority of bortezomib or daratumumab treatment for these patients. CLINICAL TRIAL REGISTRATION: NCT04210791.

The Real-World Data on Patients With Cardiac Stage IIIb AL Amyloidosis.

BACKGROUND: Morbidity and mortality of patients with immunoglobulin light chain (AL) amyloidosis are strongly associated with the severity of cardiac involvement, especial in patients with cardiac stage IIIb, but the real-world data on these patients is still limited. PATIENTS AND METHODS: A retrospective analysis was conducted on 77 patients diagnosed with cardiac stage IIIb AL amyloidosis at our center. We analyzed the clinical characteristics, treatment and outcome of the patients. RESULTS: The median age of patients was 57 years and 49.4% were male. Median serum N-terminal pro-brain natriuretic peptide (NT-proBNP) and cardiac troponin T (cTnT) were 13,384 ng/L and 0.166 ug/L, and 42 (54.5%) patients had heart failure at diagnosis. Fifty-seven (74.0%) patients received antiplasma cell treatment, and the main treatment options include bortezomib or thalidomide combined with dexamethasone. The hematologic overall response rate was 70% (28/40), and at 6-month landmark analysis, patients with hematologic responses had a higher survival rate. Cardiac and renal responses were achieved in 14 (37.8%) and 13 (32.5%) patients, respectively. After a median follow-up of 10 months (range 1-115 months), median overall survival (OS) was 18 months, and the estimated survival rates at 3, 6, and 12 months were 79.9%, 75.6%, and 54.5%, respectively. In Cox regression models, age, hypotension and cTnT were independently predictive of mortality after adjusting for heart failure. CONCLUSION: The hematologic, cardiac and renal responses were relative lower in patients with cardiac stage IIIb AL amyloidosis. The overall prognosis of patients was poor, and age, hypotension, and cTnT can be used to predict mortality.

Acute kidney injury during autologous stem cell transplantation in light chain amyloidosis with kidney involvement and their impact on prognosis.

Acute kidney injury (AKI) is a complication related to important organ dysfunction during autologous stem cell transplantation (ASCT) in light chain (AL) amyloidosis. This study aims to validate the risk factors of AKI during different periods of ASCT and the impact of AKI on long-term outcomes. 302 patients with AL amyloidosis and kidney involvement who underwent ASCT were included. The procedures from stem cell mobilization to 30 days after transplantation were categorized into four periods: Period 0 (stem cell mobilization and harvest), Period 1 (preparation), Period 2 (conditioning and transplantation), and Period 3 (engraftment). The incidence of AKI during ASCT was 27.15% (0.66% in Period 0, 6.62% in Period 1, 15.23% in Period 2, and 6.95% in Period 3). The major causes of AKI were capillary leak syndrome in Period 0, ganciclovir or sulfamethoxazole/trimethoprim in Period 1, high-dose melphalan in Period 2, and engraftment syndrome in Period 3. AKI in different periods had distinct risk factors and predictive models. AKI was a risk factor for both kidney survival and overall survival (OS). Even recovered AKI reduced 10-year kidney survival from 91.7% to 68.4% (p = 0.002) and 10-year OS from 91.1% to 77.7% (p = 0.005).

The clinical features and outcomes of systemic light chain amyloidosis with hepatic involvement.

OBJECTIVES: To evaluate the clinical characteristics and prognostic factors of hepatic systemic light chain (AL) amyloidosis. METHODS: Eighty-eight patients diagnosed AL amyloidosis with hepatic involvement between June 2004 and January 2019 were analysed retrospectively. RESULTS: The median age of the patients was 55 years old, and the male to female ratio was 2.8:1.The main clinical manifestations include edema, digestive symptoms, weight loss, fatigue and ascites. Fifty-one patients received treatment, 42 patients were suitable for therapeutic efficacy evaluation and 25 (59.5%) achieved haematologic response. The median survival time was nine months, and the survival rates at one year, three years and five years were 33.0%, 11.4% and 6.8%, respectively. The risk of death was 6.6 times that of those who did not achieve haematologic response. Multivariate analysis showed that baseline NT-proBNP ≥ 1800 pg/ml and total bilirubin ≥ 34.2 umol/L were predictive of all-cause death. CONCLUSIONS: Systemic light chain amyloidosis with hepatic involvement is associated with poor survival but rarely has specific manifestations. The significant increase of NT-proBNP and hyperbilirubinemia indicate a poor prognosis. Vigilance should be raised to the relevant clinical manifestations, early diagnosis and timely treatment can improve the prognosis. KEY MESSAGESSystemic light chain amyloidosis with hepatic involvement is associated with poor survival but rarely has specific manifestations.The significant increase of NT-proBNP and hyperbilirubinemia indicate a poor prognosis.

Clinicopathological features and outcomes of SLE patients with renal injury characterised by thrombotic microangiopathy.

OBJECTIVES: Non-immune complex (IC)-mediated renal thrombotic microangiopathy (TMA) has been reported in patients with systemic lupus erythematosus (SLE), but most studies included patients with both renal TMA and IC-mediated lupus nephritis (LN). In this study, the clinicopathological features and outcomes of renal injury characterised by only renal TMA were retrospectively analyzed. METHODS: Patients with glomerular and/or vascular TMA in the absence of subendothelial or epithelial immune deposits were screened from 2,332 biopsied of SLE patients. The TMA lesions were divided into glomerular, vascular or both. Acute tubular-interstitial injury was semi-quantitatively analyzed. The podocyte foot process effacement (FPE) was measured by electronic microscopy. RESULTS: Two hundred fifty-seven (11.0%) renal biopsies revealed TMA, among which 237 biopsies showed TMA coexisting with LN, and 20 (0.9%) biopsies had only renal TMA without or with only mesangial immune deposits. All patients manifested with acute kidney injury and haematological disorders. Among them, 11 (55%) required renal replacement therapy, 12 (60%) had nephrotic syndrome and 13 (65.0%) showed microvascular haemolytic anaemia with thrombocytopenia. Seventeen (85%) biopsies revealed both glomerular TMA and vascular TMA, two had only glomerular TMA and one had vascular TMA. Eight (40%) had no glomerular immune deposits and 12 (60%) showed only mesangial immune deposits. The acute tubulointerstitial injury in patients requiring dialysis was more severe than those not needing dialysis ((43.6 ± 24.9) % vs. (21.7 ± 20.1) %, p = 0.047). FPE of podocytes was positively correlated with proteinuria (r2 = 0.347, p = 0.006). All patients received high-dose methylprednisolone pulse therapy. Four patients received plasma exchange. The renal function of 11 patients requiring dialysis initially recovered after 16.0 (interquartile range [IQR] 9.0, 30.0) days of treatment. During the follow-up of 58.0 (IQR 36.0, 92.3) months, remission was achieved in 19 (95%) patients; only one patient had no response. No patient died or progressed to end-stage renal disease; six patients (30%) relapsed. CONCLUSION: Renal TMA, usually accompanying severe renal injury, was not uncommon in SLE patients with renal disease and should be distinguished from immune complex-mediated severe classes of LN. Early intensive immunosuppressive treatment may be associated with a good long-term renal outcome. Key Points • Most previous reports of renal TMA in SLE patients were associated with severe types of immune complex-mediated lupus nephritis; • Renal TMA with glomerular pauci-immune or only mesangial immune deposits was found in SLE patients and clinically presented with severe acute renal injury but good renal outcome; • Renal TMA should be considered as a unique type of SLE-associated renal injury.

The role of induction therapy before autologous stem cell transplantation in low disease burden AL amyloidosis patients.

BACKGROUND: Induction therapy is recommended before autologous stem cell transplantation (ASCT) for AL amyloidosis patients with high disease burden [bone marrow plasma cells (BMPCs) > 10%], but the role of induction therapy before ASCT in patients with low disease burden (BMPCs ≤ 10%) is still unknown. METHODS: A total of 227 patients with AL amyloidosis were included in this study. Among 227 patients, 124 patients received bortezomib-based induction prior to ASCT and were defined as group A, 35 patients received other chemotherapeutic induction and were defined as group B, and the other 68 patients without induction were defined as group C. We compared the differences of efficacy and prognosis between the three groups. RESULTS: The haematological overall response rates (ORR) of groups A, B and C were 91%, 67% and 75%, respectively. The complete response rates (CR) of groups A, B and C were 50%, 25% and 20%, respectively. Both the ORR and CR rates of group A were significantly higher than those of groups B and C. The renal response rates of groups A, B and C were 64%, 46% and 47%, respectively. The cardiac response rates of groups A, B and C were 74%, 45% and 40%, respectively. The renal and cardiac responses rates of group A were also significantly higher than those of the other two groups. After a median follow-up of 44 months, the median OS was not reached. The 5-year estimated overall survival (OS) rates of groups A, B and C were 81%, 57% and 67%, respectively. The median progression-free survival (PFS) was 83 months for all patients. The 5-year estimated PFS rates of groups A, B and C were 61%, 38% and 49%, respectively. Both the OS and PFS of group A were higher than those of both group B and group C. On multivariate analysis, baseline dFLC > 50 mg/L was associated with worse survival, but induction with bortezomib was associated with better survival. CONCLUSION: Our study demonstrated that low disease burden AL patients who are eligible for ASCT may benefit from bortezomib-based induction therapy.

p66Shc mediates high-glucose and angiotensin II-induced oxidative stress renal tubular injury via mitochondrial-dependent apoptotic pathway.

p66Shc, a promoter of apoptosis, modulates oxidative stress response and cellular survival, but its role in the progression of diabetic nephropathy is relatively unknown. In this study, mechanisms by which p66Shc modulates high-glucose (HG)- or angiotensin (ANG) II-induced mitochondrial dysfunction were investigated in renal proximal tubular cells (HK-2 cells). Expression of p66Shc and its phosphorylated form (p-p66Shc, serine residue 36) and apoptosis were notably increased in renal tubules of diabetic mice, suggesting an increased reactive oxygen species production. In vitro, HG and ANG II led to an increased expression of total and p-p66Shc in HK-2 cells. These changes were accompanied with increased production of mitochondrial H(2)O(2), reduced mitochondrial membrane potential, increased translocation of mitochondrial cytochrome c from mitochondria into cytosol, upregulation of the expression of caspase-9, and ultimately reduced cell survival. Overexpression of a dominant-negative Ser36 mutant p66Shc (p66ShcS36A) or treatment of p66Shc- or PKC-ß-short interfering RNAs partially reversed these changes. Treatment of HK-2 cells with HG and ANG II also increased the protein-protein association between p-p66Shc and Pin1, an isomerase, in the cytosol, and with cytochrome c in the mitochondria. These interactions were partially disrupted with the treatment of PKC-ß inhibitor or Pin1-short interfering RNA. These data suggest that p66Shc mediates HG- and ANG II-induced mitochondrial dysfunctions via PKC-ß and Pin1-dependent pathways in renal tubular cells.

Characterization of thromboelastography of patients with different pathological types of nephrotic syndrome.

To investigate the changes in blood coagulability as measured by thromboelastography (TEG) in patients with nephrotic syndrome of different etiologies as well as in patients with venous thromboembolic events (VTE).From January 2013 to October 2017, patients who were diagnosed as idiopathic membranous nephropathy (IMN), minimal change disease (MCD) and focal segmental glomerulosclerosis (FSGS) were enrolled into this retrospective study in which their clinical characteristics, including TEG variables, were investigated. According to the presence or absence of VTE, the patients with IMN were divided into 2 groups of VTE and non-VTE. The risk factors of VTE were analyzed with logistic regression.Significant differences in TEG parameters were found among the 3 groups of patients with R and K values lower, while the α-angle, maximum amplitude (MA) and confidence interval (CI) values higher, in the IMN group than those in the MCD and FSGS groups (P < .01). Multiple linear regression analysis indicated that the histologic subtype was an independent relevant factor of K time, angle, MA, and CI values. Multivariate logistic regression analysis revealed that serum albumin and CI value were independent risk factors of VTE (P < .05).The results showed that IMN patients may have higher whole blood coagulability than MCD and FSGS patients. The hypercoagulability in IMN patients may be attributed to platelet hyperactivity and the accelerated fibrin-platelet interaction. Hypoproteinemia and increased CI value were independent risk factors of VTE in IMN.

Autologous Hematopoietic Stem Cell Transplantation for Refractory Lupus Nephritis.

BACKGROUND AND OBJECTIVES: Our study evaluated the efficiency and safety of autologous hematopoietic stem cell transplantation treatment for patients with refractory lupus nephritis. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: From July 2011 to January 2015, a total of 22 patients with refractory lupus nephritis were enrolled in this study. Peripheral blood stem cells were mobilized with cyclophosphamide and granulocyte colony stimulating factor and reinfused after treatment with cyclophosphamide and antithymocyte globulin. The primary end point was the rate of remission, and secondary end points included the survival and relapse rates, changes in proteinuria, kidney function, and serology immunologic test. All complications were recorded for safety assessment. RESULTS: Twenty-two patients were enrolled and underwent stem cell mobilization. There were nine men and 13 women, with a median lupus nephritis duration of 46 (33-71) months. The mean number of CD34+ cells was (7.3±3.8)×106/kg. All patients had successful engraftment, and the median times of granulocyte and platelet engraftment were 8 (7-9) and 9 (6-10) days, respectively. The major complications of stem cell transplantation were fever and gastrointestinal tract symptoms. The treatment-related mortality was 5% (one of 22). After a median follow-up of 72 (60-80) months, 18 (82%) patients achieved completed remission, one (5%) patient achieved partial remission, and one patient had no response and received peritoneal dialysis at 12 months after transplantation. The 5-year overall survival and disease-free survival rates were 91% and 53%, respectively. Six patients experienced relapse during the follow-up, and the relapse rate was 27%. CONCLUSIONS: Autologous hematopoietic stem cell transplant could be used as a treatment option for refractory lupus nephritis, because it was relatively safe and associated with good outcomes.

Complete remission of both immunoglobulin light chain amyloidosis and psoriasis after autologous hematopoietic stem cell transplantation: A case report.

RATIONALE: Immunoglobulin light chain amyloidosis (AL amyloidosis) is characterized by the deposition of abnormal amyloid protein produced by a pathological plasma cell clone in various organs and soft tissues. Hematopoietic stem cell transplantation (HSCT) is an effective way to treat AL amyloidosis. Psoriasis is a common autoimmune disease (AID) and HSCT is a potential treatment for severe AIDs. We report a rare case of AL amyloidosis coincidence with psoriasis obtained continuous complete remission of the 2 diseases by autologous hematopoietic stem cell transplantation (ASCT). PATIENT CONCERNS: A 58-year-old man with a 30-year history of psoriasis complaining of edema and hypotension for 2 weeks was referred to our institution. His urine protein was quantified 2.83 g/day, without hematuria and decrease of glomerular filtration rate. DIAGNOSIS: Renal biopsy confirmed AL amyloidosis and multiple myeloma was excluded by bone marrow cytomorphologic examination. INTERVENTIONS: Chemotherapy regimen based on bortezomib and thalidomide had achieved hematologic partial remission, but the kidney had no response and psoriasis was still active. Furthermore, he received a standard myeloablative conditioning with high dose melphalan followed by ASCT. OUTCOMES: The erythema with slivery scales of psoriasis vulgaris gradually improved and almost disappeared after granulocyte implantation. He obtained persistent hematological complete remission, organ response and recovery of psoriasis. LESSONS: We report a rare case of AL amyloidosis coincidence with psoriasis treated by ASCT. The outcome of this patient indicated that ASCT has therapeutic values both in AL amyloidosis and AIDs.

Utility of abdominal skin plus subcutaneous fat and rectal mucosal biopsy in the diagnosis of AL amyloidosis with renal involvement.

OBJECTIVES: Skin fat biopsy of the abdominal wall is a simple and safe method for detecting amyloidosis, and rectal mucosal biopsy is also frequently used for screening for the disease; however, the sensitivity of these approaches has not been fully studied. The aim of this study was to evaluate the efficacy of skin fat biopsy combined with rectal mucosal biopsy as a screening procedure for the diagnosis of systemic immunoglobulin light-chain (AL) amyloidosis. METHODS: We retrospectively analyzed 224 AL amyloidosis patients confirmed by renal biopsy, including a test group of 165 patients and validation group of 59 patients. Surgical skin fat biopsy from the abdominal wall and rectal mucosal biopsy under endoscopy was performed to obtain specimens. Congo red staining and immunofluorescence staining with antibodies against light chains were performed to type the disease. Pathology reports were reviewed to assess the diagnostic sensitivity of skin fat biopsy and rectal mucosal biopsy. Diagnostic specificity was not examined in the present study, because no healthy volunteers and only few patients with other diseases had performed immunofluorescence staining on skin fat and rectal specimens. RESULTS: Of the 165 patients in the test group, Congo red staining of skin fat and rectal mucosal specimens was associated with a sensitivity of 89.3% and 94.8%, respectively. The sensitivity increased to 98.9% by combining both biopsy methods. Immunofluorescence stains were positive in 81.1% of patients undergoing skin fat biopsy and 84.7% of patients undergoing rectal mucosal biopsy. Immunofluorescence stains yielded positive results in 86.7% of cases combining skin fat biopsy with rectal mucosal biopsy. The diagnostic results also performed well in the validation group. CONCLUSIONS: Surgical skin biopsy including the subcutaneous fat pad can be performed safely at the bedside and is useful for diagnosing AL amyloidosis. Combining skin fat biopsy with rectal mucosal biopsy may identify amyloid deposits in almost all patients, and a negative result of both biopsies makes the diagnosis very unlikely.

Bortezomib with dexamethasone as first-line treatment for AL amyloidosis with renal involvement.

Although bortezomib has reported efficacy in light chain (AL) amyloidosis, the role of bortezomib in combination with dexamethasone (BD) as the first-line treatment for patients with AL amyloidosis has not been determined. We analyzed the outcomes of 72 consecutive unselected patients, which received primary therapy with BD in a single center. The patients were newly diagnosed with AL amyloidosis with renal (100%), cardiac (72%), hepatic (19%) or nervous system (10%) involvement and underwent a median of 2 (1-6) cycles of BD treatment. A hematologic response was achieved in 75% of the patients within a median period of 2 months, and 45% of those patients achieved a complete response. A renal response was achieved in 50% and 60% of patients at 1 year and 2 years, respectively, and a cardiac response was achieved in 40% and 46% of patients at 1 year and 2 years, respectively. After a median follow-up period of 24 months, the median duration of progression free survival was 45 months, and the estimated overall survival rates at 12 and 24 months were 83% and 76%, respectively. Baseline Eastern Cooperative Oncology Group performance status and proteinuria were associated with overall survival. The BD regimen induced high rates of rapid hematologic and organ responses in AL amyloidosis patients.

The clinical features and outcomes of systemic AL amyloidosis: a cohort of 231 Chinese patients.

BACKGROUND: Few data are available on the clinical features and outcomes of Chinese patients with systemic immunoglobulin light-chain (AL) amyloidosis. The aim of this study is to reveal the clinical picture and risk factors of disease progression in a large cohort of Chinese patients with AL amyloidosis. METHODS: Patients in the Jinling Hospital amyloidosis registry from 2003 to 2011 were studied. The clinical and laboratory information were collected from first presentation to death or until the last available clinical follow-up. The patients' survival and renal outcomes were analyzed, and the relationships between the clinical parameters and survival were also assessed. RESULTS: A total of 231 patients were enrolled in this study, all the patients studied had renal involvement. One hundred and fifty-three (66.2%) were male, and the median age at diagnosis was 56 years. A total of 198 (85.7%) cases had light-chain λ-type. One hundred and forty-seven (63.6%) cases presented as nephrotic syndrome (NS), and 25% of patients had renal insufficiency at diagnosis. Liver involvement and NS appeared to be more common in patients of κ-type amyloidosis, and renal impairment is more severe in κ-type amyloidosis. The median survival time of all patients was 36.3 months, and the 1-, 2-, 3- and 5-year cumulative survival rates were 67, 53, 48 and 35%, respectively. Multivariate COX analysis showed that age, hepatic involvement and heart involvement can significantly influence survival in these patients. The median time that patients remained dialysis free was 50 months. The percentage of patients that remained dialysis free at 1, 2, 3 and 5 years were 78, 69, 62 and 37%, respectively. Multivariate COX analysis showed that serum creatinine and hypotension were the important risk factors of renal failure. CONCLUSION: λ-Type is the most dominant type of AL amyloidosis in Chinese patients. The survival of patients with AL amyloidosis is poor. The risk factors included heart and hepatic involvement, hypotension and impairment of renal function. The high serum creatinine level and hypotension at diagnosis are associated with poor renal outcome.