Objective
To investigate kidney function change during adrenalectomy in patients with primary aldosteronism and assess predictors of kidney function decline.
Methods
The present study included 90 ...patients who underwent adrenalectomy for primary aldosteronism between 2004 and 2017. Kidney function was evaluated 1 month after surgery. Predictors associated with a ≥10% decline in the estimated glomerular filtration rate were investigated. Kidney parenchymal volume was compared before and after surgery in 10 patients using volumetric studies.
Results
The mean estimated glomerular filtration rate decline in the total cohort at 1 month after surgery was 13.3% (before: 72.9 mL/min/1.73 m2, after: 64.9 mL/min/1.73 m2, P < 0.0001). The mean serum plasma aldosterone concentration (before: 373 pg/mL vs after: 78 pg/mL, P < 0.0001) and potassium level (before: 3.7 mEq/L vs after: 3.9 mEq/L, P = 0.0001) were also significantly different after surgery. Age (odds ratio 6.37, P = 0.0006), preoperative plasma aldosterone concentration (odds ratio 3.12, P = 0.0209) and preoperative serum potassium level (odds ratio 2.87, P = 0.0010) were independent predictors of a ≥10% decline in estimated glomerular filtration rate. Volumetric studies in 10 patients showed that mean postoperative parenchymal volume was significantly decreased compared with the preoperative volume (263 cc vs 312 cc, P = 0.0003), with decreases in estimated glomerular filtration rate from 63 to 56 mL/min/1.73 m2 (P = 0.0146).
Conclusions
Kidney function deterioration after adrenalectomy can be detected in patients with primary aldosteronism. Age, preoperative plasma aldosterone concentration and preoperative potassium level are significant predictors of a decrease in the estimated glomerular filtration rate. Normal parenchymal volume decreases in line with renal functional deterioration.
We reviewed the clinical efficacy of axitinib after nivolumab treatment failure in patients with metastatic renal cell carcinoma.
Abstract
We reviewed the clinical efficacy of axitinib after ...nivolumab treatment failure in six patients with metastatic renal cell carcinoma (RCC); the patients had received nivolumab treatment following vascular endothelial growth factor receptor (VEGFR) inhibitors. Most had undergone radical nephrectomy; five had clear-cell carcinoma and acquired cystic disease-associated carcinoma. The patients were finally diagnosed with progressive disease during nivolumab treatment. Immediately after nivolumab treatment failure, one patient receiving pazopanib had an adverse event soon after, and subsequently received axitinib, which the others received. The size of the metastatic tumors treated with axitinib after nivolumab was on average 33.9% smaller. Following treatment, three patients experienced partial response with remarkable tumor shrinkage and three had stable disease (SD), of which most maintained for >5 months. One patient with SD died from gradual tumor progression after axitinib treatment. Axitinib treatment after nivolumab treatment failure can be beneficial for some patients with metastatic RCC.
Heat shock protein 90 (HSP90), a molecular chaperone associated with the activation of client proteins, was recently reported to play an important role in immunologic reactions. To date, the role of ...HSP90 in solid organ transplantations has remained unknown. The aim of this study was to evaluate the relationship between serum HSP90α levels and acute allograft rejection after organ and tissue transplantation using serum samples from kidney allograft recipients, an in vitro antibody-mediated rejection model, and a murine skin transplantation.
Serum HSP90α levels were significantly higher in kidney recipients at the time of acute rejection (AR) than in those with no evidence of rejection. In most cases with AR, serum HSP90 decreased to baseline after the treatment. On the other hand, serum HSP90α was not elevated as much in patients with chronic rejection, calcineurin inhibitor nephrotoxicity, or BK virus nephropathy as in AR patients. In vitro study showed that HSP90α concentration in the supernatant was significantly higher in the supernatant of human aortic endothelial cells cocultured with specific anti-HLA IgG under complement attack than in that of cells cocultured with nonspecific IgG. In mice receiving skin transplantation, serum HSP90α was elevated when the first graft was rejected and the level further increased during more severe rejection of the second graft.
The results suggest that HSP90α is released into the serum by cell damage due to AR in organ and tissue transplantation, and it is potentially a new biomarker to help detect AR in kidney recipients.
Objective
To evaluate the impact of pretransplant body mass index on graft failure and mortality in Japanese patients undergoing living kidney transplant.
Methods
A cohort of 888 living kidney ...transplant recipients who received standard immunosuppressive therapy between 2000 and 2013 were identified from the Japan Academic Consortium of Kidney Transplantation database. Pretransplant body mass index was divided into three categories according to the following tertiles: <19.4, 19.5–22.2 and ≥22.3 kg/m2. A multivariable time‐to‐event analysis was carried out.
Results
Estimated hazard ratios of the body mass index effects regarding graft failure were 1.62 (95% confidence interval 0.83–3.18) for the first tertile and 2.20 (95% confidence interval 1.24–3.90) for the third tertile. Patient mortality was 1.21 (95% confidence interval 0.32–4.54) for the first tertile and 1.52 (95% confidence interval 0.56–4.13) for the third tertile. In a subgroup analysis, the effects of body mass index according to sex were substantially heterogeneous (P = 0.029 for interaction). Pretransplant body mass index had a non‐linear J‐shaped association with graft failure that resulted from qualitative interaction between body mass index and the recipient's sex.
Conclusions
Sex differences and interaction effects must be considered when evaluating the effects of pretransplant body mass index on post‐transplant outcomes in Japanese patients undergoing living kidney transplant.
Abstract
Objective
Studies assessing outcome improvements over a long period according to systemic therapy strategies for metastatic renal cell carcinoma using real-world data, including the results ...of the recent era of immune checkpoint inhibitors, are limited. Herein, we retrospectively evaluated patients who were diagnosed with metastatic renal cell carcinoma over a 40-year span.
Methods
Patients were classified into four groups based on when their metastases were diagnosed as follows: (i) the pre-cytokine era (1980–1986), (ii) the cytokine era (1987–2007), (iii) the molecular-targeted therapy (mTT) era (2008 to August 2016) and (iv) the immune checkpoint inhibitor era (September 2016 to 2018). The immune checkpoint inhibitor era consisted of second- or later-line nivolumab. Overall survival from the diagnoses of metastases was evaluated.
Results
In total, 576 patients were evaluated, including 22 (3.82%), 231 (40.1%), 253 (43.9%) and 70 (12.2%) patients from the pre-cytokine, cytokine, molecular-targeted therapy and immune checkpoint inhibitor eras, respectively. The overall survival significantly improved with each successive era (median: 13.1 vs. 24.5 vs. 44.4 months vs. not reached in pre-cytokine vs. cytokine vs. molecular-targeted therapy vs. immune checkpoint inhibitor eras, P < 0.0001). The implementation of molecular-targeted therapy improved overall survival compared with that of cytokine (cytokine vs. molecular-targeted therapy eras, P < 0.0001). Multivariate analysis demonstrated that the era was an independent factor for overall survival (P < 0.0001), together with histopathological type; metastasis status (i.e. synchronous or metachronous); systemic therapy status (i.e. absence or presence) and bone, liver or lymph node metastasis status (all, P < 0.05).
Conclusion
This retrospective study of real-world data indicated that metastatic renal cell carcinoma outcomes improved with successive systemic therapy paradigms.
We assessed outcome change in 576 patients with metastatic renal cell carcinoma over 40-year span. The outcome improved with successive systemic therapy paradigms including an immune checkpoint inhibitor era.
Abstract
Objectives
To investigate the long-term follow-up outcomes of nivolumab monotherapy for previously treated metastatic renal cell carcinoma, using real-world data.
Methods
A total of 121 ...patients were treated with nivolumab monotherapy as subsequent therapy after the failure of prior tyrosine kinase inhibitor therapy between January 2013 and December 2021 at four affiliated institutions. To evaluate the outcome after 2 years or more, we selected patients in whom nivolumab therapy was started in December 2019 or earlier because data collection was performed until the end of December 2021.
Results
Seventy-four patients were evaluated. During the median follow-up period of 25.8 months, 62 (84%) and 40 (54%) patients had disease progression and died, respectively. Nivolumab was administered as second-line therapy in 43 patients (58%). The median progression-free survival and overall survival were 5.52 and 31.1 months, respectively, and objective response rate was 36%. There was no difference in progression-free survival or overall survival based on the treatment line of nivolumab (P = 0.915, P = 0.559). The magnitude of tumor response and development of immune-related adverse events were significantly associated with progression-free survival (P < 0.0001, P < 0.0001, respectively) and overall survival (P < 0.0001, P = 0.0002, respectively). Treatment-related adverse events developed in 38 patients (51%), including 33 (45%) who had immune-related adverse events. Steroid administration was needed in nine patients (12%).
Conclusions
The present real-world multi-institution study with long-term follow-up data demonstrates that nivolumab monotherapy is effective for previously treated metastatic renal cell carcinoma, prolonging survival, improving tumor response and has a manageable safety profile.
The real-world data with long-term follow-up indicated that nivolumab monotherapy is effective for previously treated metastatic renal cell carcinoma, prolonging survival, improving tumor response, and has a manageable safety profile.
Objectives
To compare the efficacy of nivolumab with that of molecular‐targeted therapy as a second‐line therapy for metastatic renal cell carcinoma using real‐world data.
Methods
We retrospectively ...evaluated patients who received nivolumab or molecular‐targeted therapy after the failure of first‐line molecular‐targeted therapy between January 2008 and December 2019 at two Japanese institutions. Progression‐free survival and overall survival after the initiation of second‐line therapy were calculated using the Kaplan‐Meier method and compared using the log‐rank test. Objective response rate was assessed based on the Response Evaluation Criteria in Solid Tumors version 1.1.
Results
Among 159 patients, 43 (27%) and 116 (73%) patients received nivolumab and molecular‐targeted therapy as second‐line therapy, respectively. During follow up (median 11.1 months), 129 (81%) and 98 (62%) patients had disease progression and died, respectively. Progression‐free survival was comparable between the two treatments (median 5.06 vs 5.95 months, P = 0.881), whereas overall survival was significantly longer with nivolumab than with molecular‐targeted therapy (not reached vs 13.0 months, P = 0.0008). Multivariate analysis further showed that nivolumab therapy was an independent favorable factor for overall survival (hazard ratio 0.33, P = 0.0007). In 151 patients with eligible radiographic data, the objective response rate was significantly higher in nivolumab than in molecular‐targeted therapy (n = 14/41 34% vs n = 20/110 18%, P = 0.0485).
Conclusions
Real‐world data analysis suggests superior efficacy of nivolumab over molecular‐targeted therapy as second‐line therapy for metastatic renal cell carcinoma.
Summary
Acceptable outcomes of donor‐specific antibody (DSA)‐positive living kidney transplantation (LKT) have recently been reported. However, LKT in crossmatch (XM)‐positive patients remains at ...high‐risk and requires an optimal desensitization protocol. We report our intermediate‐term outcomes of XM‐positive LKT vs. XM‐negative LKT in patients who underwent LKT between January 2012 and June 2015 in our institution. The rate of acute antibody‐mediated rejection (ABMR) within 90 days postoperation, graft function, and patient, and graft survival rates at 4 years were investigated. Patients were divided into three groups: XM−DSA− (n = 229), XM−DSA+ (n = 36), and XM + DSA+ (n = 15). The XM + DSA+ group patients underwent desensitization with high‐dose intravenous immunoglobulin, plasmapheresis, and rituximab. The rates of ABMR within 90 days in the XM−DSA−, XM−DSA+, and XM + DSA+ groups were 1.3%, 9.4%, and 60.0%, respectively (P < 0.001). There were no significant differences in the graft function throughout the observational period, the 4‐year patient or graft survival rates among three groups. This study showed that intermediate‐term outcomes of XM‐positive LKT were comparable to XM‐negative LKT. However, our current desensitization protocol cannot avert ABMR within 90 days, and XM positivity is still a significant risk factor for ABMR. Further refinement of the current desensitization regimen is required.
We investigated the efficacy of nivolumab treatment in patients with metastatic renal cell carcinoma who discontinued nivolumab treatment due to reasons other than disease progression. Of the 34 ...patients, 3 patients discontinued nivolumab therapy due to adverse events and were subsequently observed without additional treatment. The first patient discontinued nivolumab after 14 cycles of treatment due to type 1 diabetes mellitus and has maintained partial remission for 8 months. The second patient discontinued nivolumab after 11 cycles of treatment due to interstitial pneumonitis, and durable response was confirmed for 5 months. However, multiple lung lesions reappeared at 6 months after discontinuing nivolumab. The third patient discontinued nivolumab due to elevated liver enzymes after three cycles of treatment. At the time of discontinuation, a new liver lesion appeared, but the lesion decreased in size at 6 months after discontinuation. In the present study, a relatively durable response was observed in three patients who discontinued nivolumab without additional treatment.
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