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Proliferative glomerulonephritis with monoclonal IgG deposits in two kidney allografts successfully treated with rituximab.

Fri, 06/16/2017 - 12:45
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Proliferative glomerulonephritis with monoclonal IgG deposits in two kidney allografts successfully treated with rituximab.

Clin Kidney J. 2017 Jun;10(3):405-410

Authors: Merhi B, Patel N, Bayliss G, Henriksen KJ, Gohh R

Abstract
Proliferative glomerulonephritis with monoclonal immunoglobulin G deposit (PGNMID), a recently described pathologic entity in native kidneys, has been recognized in kidney transplant patients, where it can present as either recurrent or de novo disease. There is no definitive treatment to date, in either population. Here, we present two cases of PGNMID in kidney allografts that illustrate the challenges of diagnostic approach and highlight the allograft outcome after treatment with rituximab as a potential treatment of this condition.

PMID: 28616219 [PubMed - in process]

Is chronic kidney disease-mineral and bone disorder associated with the presence of endothelial progenitor cells with a calcifying phenotype?

Fri, 06/16/2017 - 12:45
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Is chronic kidney disease-mineral and bone disorder associated with the presence of endothelial progenitor cells with a calcifying phenotype?

Clin Kidney J. 2017 Jun;10(3):389-396

Authors: Cianciolo G, Capelli I, Cappuccilli M, Scrivo A, Donadei C, Marchetti A, Rucci P, La Manna G

Abstract
Background: Chronic kidney disease-mineral and bone disorder (CKD-MBD) has been implicated in vascular calcification pathogenesis. CKD-MBD results in alterations in the number and function of circulating endothelial progenitor cells (EPCs), physiological regulators of angiogenesis and vessel repair, commonly defined as proangiogenic progenitor cells (PACs) by the antigen pattern CD34+CD133+KDR+CD45- and putative EPCs by the pattern CD34+CD133-KDR+CD45-. These cells might acquire a calcifying phenotype in CKD-MBD, expressing mineralization biomarkers. We investigated the expression of vitamin D receptor (VDR) and osteocalcin (OC) on EPCs of healthy individuals and haemodialysis patients, and their possible associations with circulating biomarkers of inflammation and vascular calcification. Methods: We compared EPC counts, expressing VDR or OC, in 23 healthy subjects versus 53 haemodialysis patients, 17 of them without vitamin D receptor agonist (VDRA) therapy and 35 treated with calcitriol (n  =  17) or paricalcitol (n  =  18). The correlations with serum levels of inflammatory and calcification indexes were also analysed. Results: All subsets expressing VDR or OC were significantly higher in haemodialysis patients compared with healthy controls, but PACs were increased only in VDRA treatment subgroup, while putative EPCs showed a similar rise also in untreated patients. In VDRA-untreated patients, OC+  PACs correlated positively with calcium levels, while in VDRA-treated patients, VDR+ PACs correlated positively with interleukin 6 levels, and OC+  PACs correlated positively 25-hydroxyvitamin D levels. Conclusions: Our data suggest that in CKD-MBD, EPCs undergo an endothelial-to-procalcific shift, representing a risk factor for vascular calcification. A link between mineral disorders and vitamin D replacement therapy emerged, with potential adverse effects for CKD patients.

PMID: 28616217 [PubMed - in process]

Acute kidney injury in patients with severe sepsis or septic shock: a comparison between the 'Risk, Injury, Failure, Loss of kidney function, End-stage kidney disease' (RIFLE), Acute Kidney Injury Network (AKIN) and Kidney Disease: Improving Global...

Fri, 06/16/2017 - 12:45
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Acute kidney injury in patients with severe sepsis or septic shock: a comparison between the 'Risk, Injury, Failure, Loss of kidney function, End-stage kidney disease' (RIFLE), Acute Kidney Injury Network (AKIN) and Kidney Disease: Improving Global Outcomes (KDIGO) classifications.

Clin Kidney J. 2017 Jun;10(3):332-340

Authors: Pereira M, Rodrigues N, Godinho I, Gameiro J, Neves M, Gouveia J, Costa E Silva Z, Lopes JA

Abstract
PURPOSE: Using the Risk, Injury, Failure, Loss of kidney function, End-stage kidney disease (RIFLE), Acute Kidney Injury Network (AKIN) and Kidney Disease: Improving Global Outcomes (KDIGO) systems, the incidence of acute kidney injury (AKI) and their ability to predict in-hospital mortality in severe sepsis or septic shock was compared.
MATERIALS AND METHODS: We performed a retrospective analysis of 457 critically ill patients with severe sepsis or septic shock hospitalized between January 2008 and December 2014. Multivariate logistic regression was employed to evaluate the association between the RIFLE, AKIN and KDIGO systems with in-hospital mortality. Model fit was assessed by the goodness-of-fit test and discrimination by the area under the receiver operating characteristic (AUROC) curve. Statistical significance was defined as P < 0.05.
RESULTS: RIFLE (84.2%) and KDIGO (87.5%) identified more patients with AKI than AKIN (72.8%) (P < 0.001). AKI defined by AKIN and KDIGO was associated with in-hospital mortality {AKIN: adjusted odds ratio [OR] 2.3[95% confidence interval (CI) 1.3-4], P = 0.006; KDIGO: adjusted OR 2.7[95% CI 1.2-6.2], P = 0.021} while AKI defined by RIFLE was not [adjusted OR 2.0 (95% CI 1-4), P = 0.063]. The AUROC curve for in-hospital mortality was similar between the three classifications (RIFLE 0.652, P < 0.001; AKIN 0.686, P < 0.001; KDIGO 0.658, P < 0.001).
CONCLUSIONS: RIFLE and KDIGO diagnosed more patients with AKI than AKIN, but the prediction ability for in-hospital mortality was similar between the three systems.

PMID: 28616211 [PubMed - in process]

Preoperative chronic kidney disease predicts poor oncological outcomes after radical cystectomy in patients with muscle-invasive bladder cancer.

Fri, 06/16/2017 - 12:45
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Preoperative chronic kidney disease predicts poor oncological outcomes after radical cystectomy in patients with muscle-invasive bladder cancer.

Oncotarget. 2017 May 29;:

Authors: Hamano I, Hatakeyama S, Iwamura H, Fujita N, Fukushi K, Narita T, Hagiwara K, Kusaka A, Hosogoe S, Yamamoto H, Tobisawa Y, Yoneyama T, Yoneyama T, Hashimoto Y, Koie T, Ito H, Yoshikawa K, Kawaguchi T, Ohyama C

Abstract
OBJECTIVE: To evaluate the impact of preoperative chronic kidney disease (CKD) on oncologic outcomes in muscle-invasive bladder cancer patients who underwent radical cystectomy.
METHODS: A total of 581 patients who underwent radical cystectomy at four medical centers between January 1995 and February 2017 were examined retrospectively. We investigated oncologic outcomes, including progression-free, cancer-specific, and overall survival (PFS, CSS, and OS, respectively) stratified by preoperative CKD status (pre-CKD vs. non-CKD). We performed a Cox proportional hazards regression analysis using inverse probability of treatment weighting (IPTW) to evaluate the impact of preoperative CKD on prognosis and developed the prognostic factor-based risk stratification nomogram.
RESULTS: Of the 581 patients, 215 (37%) were diagnosed with CKD before radical cystectomy. Before the background adjustment, PFS, CSS, and OS after radical cystectomy were significantly lower in the pre-CKD group compared to the non-CKD group. Background-adjusted IPTW analysis showed that preoperative CKD was significantly associated with poor PFS, CSS, and OS after radical cystectomy. The nomogram for predicting 5-year PFS and OS probability showed significant correlation with actual PFS and OS (c-index = 0.73 and 0.77, respectively).
CONCLUSIONS: Muscle-invasive bladder cancer patients with preoperative CKD had a significantly lower survival probability than those without CKD.

PMID: 28615535 [PubMed - as supplied by publisher]

End-stage kidney disease in patient with epidermolysis bullosa - what are the treatment options? - case report.

Fri, 06/16/2017 - 12:45
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End-stage kidney disease in patient with epidermolysis bullosa - what are the treatment options? - case report.

BMC Nephrol. 2017 Jun 14;18(1):193

Authors: Małecki M, Domański M, Ciechanowski K

Abstract
BACKGROUND: Epidermolysis bullosa is a group of diseases caused by mutations in genes for proteins responsible for cells' anchorage at the dermo-epidermal junction. Their common feature are dysfunctional or even absent connections between cells. The typical clinical sign is the formation of blisters, with possible excessive scarring, in response to minimal skin irritation. End stage renal disease may be one of the comorbidities in patients with epidermolysis bullosa. The implementation of renal replacement therapy may be very difficult in this population. This is mainly due to problems in obtaining the proper dialysis access. The choice of appropriate method may be crucial for patient's survival.
CASE PRESENTATION: We present a case of 29-year-old woman with Epidermolysis bullosa caused by laminin 5 gene mutation. The patient suffered from additional conditions: blindness, complete bilateral sensorineural deafness and oesophageal stenosis. When end stage renal disease was diagnosed, the problem of renal replacement therapy had to be faced. There have been few reports concerning ESRD in this specific group of patients in the available literature. In most of them the prognosis was very poor. Nevertheless, we were very determined to overcome all the difficulties. Special procedures and cooperation with the patient's family allowed us to consider kidney transplantation as a treatment option.
CONCLUSION: There should be no limitations in renal replacement therapy in patients with epidermolysis bullosa. Haemodialysis, peritoneal dialysis and kidney transplantation are all possible treatment options. Nevertheless, either method requires special procedures.

PMID: 28615054 [PubMed - in process]

Improving long-term outcomes after pediatric renal transplantation by addressing dyslipidemia.

Fri, 06/16/2017 - 12:45
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Improving long-term outcomes after pediatric renal transplantation by addressing dyslipidemia.

Pediatr Transplant. 2017 05;21(3):

Authors: Filler G, Medeiros M

PMID: 28370889 [PubMed - indexed for MEDLINE]

Extracorporeal Membrane Oxygenation in New York State: Trends, Outcomes, and Implications for Patient Selection.

Fri, 06/16/2017 - 12:45
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Extracorporeal Membrane Oxygenation in New York State: Trends, Outcomes, and Implications for Patient Selection.

Circ Heart Fail. 2016 Dec;9(12):

Authors: Batra J, Toyoda N, Goldstone AB, Itagaki S, Egorova NN, Chikwe J

Abstract
BACKGROUND: Utilization of extracorporeal membrane oxygenation (ECMO) is expanding despite limited outcome data defining appropriate use.
METHODS AND RESULTS: To quantify determinants of early and 1-year survival after ECMO in adult patients, we conducted a retrospective cohort analysis of 1286 patients aged ≥18 years who underwent ECMO in New York State from 2003 to 2014. Median follow-up time was 4.9 months (range, 0-12 months). ECMO utilization increased from 13 patients in 8 hospitals in 2003 to 330 patients in 30 hospitals in 2014. Compared with patients undergoing ECMO before 2009, later patients were older (54.4 versus 52.3 years; P=0.013) and more likely to have major comorbidity including chronic kidney disease (25.2% versus 13.2%; P=0.02) and liver disease (20.0% versus 10.7%; P=0.001). In the overall cohort, 30-day mortality was 52.2% (95% confidence interval, 49.5-54.9). Mortality at 30 days was 65.2% for patients aged ≥75 years (n=73/112) and 74.6% in patients who required cardiopulmonary resuscitation (n=91/122). Survival at 1 year was 38.4% (95% confidence interval, 35.7-41.0). The 30-day mortality and 1-year survival improved across the study period. In multivariable analysis, earlier year of ECMO, lower hospital volume, indication for ECMO after a cardiac procedure, cardiopulmonary resuscitation before ECMO placement, and age >65 years were independent predictors of worse survival.
CONCLUSIONS: Outcomes of ECMO have improved despite increasing comorbidity. Extreme mortality after ECMO in elderly patients and patients requiring cardiopulmonary resuscitation indicates that less invasive therapeutic or palliative modalities may be more appropriate in this end-of-life setting.

PMID: 27940495 [PubMed - indexed for MEDLINE]

Adiponectin Fractions Influence the Development of Posttransplant Diabetes Mellitus and Cardiovascular Disease in Japanese Renal Transplant Recipients.

Fri, 06/16/2017 - 12:45
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Adiponectin Fractions Influence the Development of Posttransplant Diabetes Mellitus and Cardiovascular Disease in Japanese Renal Transplant Recipients.

PLoS One. 2016;11(10):e0163899

Authors: Adachi H, Nakayama K, Hayashi N, Matsui Y, Fujimoto K, Yamaya H, Tonami H, Yokoyama H

Abstract
BACKGROUND: A few studies have investigated the role of adiponectin fraction for cardiovascular disease (CVD) in RTx recipients.
SUBJECTS AND METHODS: We studied 57 adult subjects (39 males, 18 females; 10 cadaveric donors) with at least three years of allograft survival (median 251 months). We examined clinical backgrounds such as treated drugs, blood pressure (BP, mmHg), body mass index (BMI), and blood chemistry including cholesterol (total, LDL-C, HDL-C), glucose, glycated hemoglobin (HbA1c), and serum high and low-molecular-weight (HMW/LMW) ADPN fractions with regard to the associations of the visceral and subcutaneous fat areas on CT scan. We also analyzed the associations of CVD and post-transplant diabetes (PTDM) with ADPN fractions and the fat areas.
RESULTS: The visceral fat area was inversely correlated with serum HMW and LMW ADPN levels and HMW ADPN ratio (r = -0.400, p = 0.002 and r = -0.296, p = 0.025 and r = -0.444, p<0.001, respectively). Furthermore, the visceral fat area was positively with the LMW ADPN ratio (r = 0.467, p<0.001), but no significant correlation was noted between the subcutaneous fat area and the ADPN ratio. On multiple regression analysis, eGFR and the visceral fat area were significant reducing factors of HMW ADPN levels, and the alteration of eGFR was identified as an increasing factor of HMW ADPN levels. Patients with CVD had larger visceral fat area (p = 0.004), lower HMW ADPN ratio (p = 0.022) and higher LMW ADPN ratio (p = 0.049). In addition, the higher HMW ADPN ratio and statin treatment were identified as reducing factors of the development of CVD, but the LDL-C level was an aggravating factor. Moreover, the higher LMW ADPN ratio and the visceral fat area were aggravating factors of PTDM.
CONCLUSION: Even in Japanese renal transplant recipients, visceral fat area and ADPN fractions were significant factors for the development of both CVD and PTDM.

PMID: 27706207 [PubMed - indexed for MEDLINE]

Epstein-Barr virus associated multi-organ smooth muscle tumours following renal transplantation.

Fri, 06/16/2017 - 12:45
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Epstein-Barr virus associated multi-organ smooth muscle tumours following renal transplantation.

Dig Liver Dis. 2016 Aug;48(8):973

Authors: Karthik SV, Pang YH, Lau P, Aw MM

PMID: 27158124 [PubMed - indexed for MEDLINE]

Multilevel brown tumors of the spine in a patient with severe secondary hyperparathyroidism A case report and review of the literature.

Fri, 06/16/2017 - 12:45
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Multilevel brown tumors of the spine in a patient with severe secondary hyperparathyroidism A case report and review of the literature.

Ann Ital Chir. 2016 Mar 31;87(ePub):

Authors: Salamone D, Muresan S, Muresan M, Neagoe R

Abstract
BACKGROUND: The brown tumour is an extreme form of osteitis fibrosa cystica, representing a serious complication of the advanced primary or secondary hyperparathyroidism. It occurs in settings of high levels parathyroid hormone, like in primary or secondary hyperparathyroidism, with a frequency of 3-4% and 1.5-13% respectively, usually affecting young people.
CASE REPORT: The authors report a case of a 45 years old woman on long-term hemodialysis, with severe secondary hyperparathyroidism. The main clinical complaints were neck pain, lower thoraco-lumbar back pain, persistent left groin pain, and bilateral lower extremities weakness. The computed tomography scan revealed multiple spine brown tumors affecting the cervical, thoracic and lumbar level. After an initial partial response to the treatment of two years with Cinacalcet, a deterioration of the secondary hyperparathyroidism occurred (hypercalcemia, hyperphosphatemia) and the patient was referred for parathyroidectomy. The patient underwent total parathyroidectomy with auto-transplantation, with a positive postoperative result.
CONCLUSIONS: Secondary hyperparathyroidism can lead, during its course, to osteolytic bone lesions called brown tumors. If the medical treatment fails, the surgical removal of the parathyroid glands with autotransplant remains the only treatment of the bone lesions progression. Reviewing the relevant literature in English (until March 2015), we found 24 cases of symptomatic vertebral brown tumors. To the authors' knowledge, this is the first case which describes a multilevel spine involvement (more than two), and the fifth describing a cervical localization.
KEY WORDS: Hypocalcaemia, Secondary hyperparathyroidism, Spine brown tumors.

PMID: 27064191 [PubMed - indexed for MEDLINE]

Assessing rejection-related disease in kidney transplant biopsies based on archetypal analysis of molecular phenotypes.

Thu, 06/15/2017 - 15:45

Assessing rejection-related disease in kidney transplant biopsies based on archetypal analysis of molecular phenotypes.

JCI Insight. 2017 Jun 15;2(12):

Authors: Reeve J, Böhmig GA, Eskandary F, Einecke G, Lefaucheur C, Loupy A, Halloran PF, MMDx-Kidney study group

Abstract
Conventional histologic diagnosis of rejection in kidney transplants has limited repeatability due to its inherent requirement for subjective assessment of lesions, in a rule-based system that does not acknowledge diagnostic uncertainty. Molecular phenotyping affords opportunities for increased precision and improved disease classification to address the limitations of conventional histologic diagnostic systems and quantify levels of uncertainty. Microarray data from 1,208 kidney transplant biopsies were collected prospectively from 13 centers. Cross-validated classifier scores predicting the presence of antibody-mediated rejection (ABMR), T cell-mediated rejection (TCMR), and 5 related histologic lesions were generated using supervised machine learning methods. These scores were used as input for archetypal analysis, an unsupervised method similar to cluster analysis, to examine the distribution of molecular phenotypes related to rejection. Six archetypes were generated: no rejection, TCMR, 3 associated with ABMR (early-stage, fully developed, and late-stage), and mixed rejection (TCMR plus early-stage ABMR). Each biopsy was assigned 6 scores, one for each archetype, representing a probabilistic assessment of that biopsy based on its rejection-related molecular properties. Viewed as clusters, the archetypes were similar to existing histologic Banff categories, but there was 32% disagreement, much of it probably reflecting the "noise" in the current histologic assessment system. Graft survival was lowest for fully developed and late-stage ABMR, and it was better predicted by molecular archetype scores than histologic diagnoses. The results provide a system for precision molecular assessment of biopsies and a new standard for recalibrating conventional diagnostic systems.

PMID: 28614805 [PubMed - as supplied by publisher]

PSA declines and survival in patients with metastatic castration-resistant prostate cancer treated with enzalutamide: A retrospective case-report study.

Thu, 06/15/2017 - 15:45

PSA declines and survival in patients with metastatic castration-resistant prostate cancer treated with enzalutamide: A retrospective case-report study.

Medicine (Baltimore). 2017 Jun;96(24):e6817

Authors: Bosso D, Pagliuca M, Sonpavde G, Pond G, Lucarelli G, Rossetti S, Facchini G, Scagliarini S, Cartenì G, Daniele B, Morelli F, Ferro M, Puglia L, Izzo M, Montanaro V, Bellelli T, Vitrone F, De Placido S, Buonerba C, Di Lorenzo G

Abstract
RATIONALE: PSA responses have been associated with a survival benefit in patients treated with enzalutamide in retrospective analyses.
PATIENT CONCERNS: However the prognostic value of PSA declines in highly pretreated patients receiving enzalutamide remains to be defined.
DIAGNOSES AND INTERVENTATIONS: Medical records of patients with documented mCRPC treated with enzalutamide between September 2011 and August 2016 were reviewed at multiple participating centers and assessed for overall survival (OS), PSA variations, and other variables of interest. Univariable and multivariable analyses were conducted.
OUTCOMES: A total of 129 patients received enzalutamide. PSA response rates (>50% PSA declines) were 58/119 (48.7%), 58/115 (50.4%), 54/110 (49.1%), and 47/91 (51.7%) at weeks 4, 8, 12, and 16, respectively. Having a PSA response was a statistically significant prognostic factor of improved OS at 8 and 12 weeks in univariable analysis, whereas it was significant at 12 weeks in the multivariable analysis. Patients treated with enzalutamide had a median OS of 7.8 months.
LESSONS: Our study supports the prognostic value of PSA declines in heavily treated patients receiving enzalutamide.

PMID: 28614217 [PubMed - in process]

Anti-CD20 blocker Rituximab in Kidney Transplantation.

Thu, 06/15/2017 - 15:45

Anti-CD20 blocker Rituximab in Kidney Transplantation.

Transplantation. 2017 Jun 13;:

Authors: Sood P, Hariharan S

Abstract
Rituximab is a chimeric anti-CD20 monoclonal protein used in various clinical scenarios in kidney transplant recipients. However, its evidence-based use there remains limited due to lack of controlled studies, limited sample size, short follow-up and poorly defined endpoints. Rituximab is indicated for CD20+ PTLD. It may be beneficial for treating recurrent MN and recurrent allograft ANCA vasculitis and possibly for recurrent FSGS. Rituximab, in combination with IVIG/PP, appears to decrease antibody level and increase the odds of transplantation in sensitized recipients. The role of Rituximab in ABOi transplant remains unclear, as similar outcomes are achieved without its use. Rituximab is not efficacious in ABMR/CAMR. Strict RCTs are necessary to elucidate its true role in these settings.

PMID: 28614191 [PubMed - as supplied by publisher]

MicroRNA-423-5p facilitates hypoxia/reoxygenation-induced apoptosis in renal proximal tubular epithelial cells by targeting GSTM1 via endoplasmic reticulum stress.

Thu, 06/15/2017 - 15:45

MicroRNA-423-5p facilitates hypoxia/reoxygenation-induced apoptosis in renal proximal tubular epithelial cells by targeting GSTM1 via endoplasmic reticulum stress.

Oncotarget. 2017 May 30;:

Authors: Yuan XP, Liu LS, Chen CB, Zhou J, Zheng YT, Wang XP, Han M, Wang CX

Abstract
It has been reported that microRNAs (miRs) can regulate renal response to acute injury and members of them are believed to be important in maintenance of renal function and development of renal injury. We investigated the actions of microRNA-423-5p (miR-423-5p) and glutathione-S-transferase (GST) M1 after acute kidney injury. MiR-423-5p was up-regulated and GSTM1 was down-regulated in human kidney (HK-2) cells subjected to hypoxia/reoxygenation (H/R) and in rat kidneys subjected to ischemia/reperfusion (I/R) injury. Dual luciferase assays revealed miR-423-5p binding to the 3' untranslated region of GSTM1. Proliferation was lower and apoptosis, ER stress and oxidative stress were all higher in H/R-treated HK-2 cells transfected with or without miR-423-5p mimics and GSTM1 siRNA than in the same cells transfected with miR-423-5p inhibitors and a GSTM1 expression vector. Increased miR-423-5p and decreased GSTM1 mRNA and protein levels were observed in rat kidneys on days 1, 2 and 7 after I/R. Levels had normalized by days 14 and 21. On day 3 after treatment, rats receiving I/R or I/R plus miR-423-5p mimics exhibited higher serum creatinine and urea nitrogen levels than rats receiving I/R plus a miR-423-5p inhibitor. MiR-423-5p and lower GSTM1 mRNA and protein levels were higher in the I/R and I/R plus miR-423-5p mimic groups than in the I/R plus miR-423-5p inhibitors group. These findings demonstrate that after acute kidney injury, miR-423-5p induces ER stress and oxidative stress by inhibiting GSTM1and suppresses repair.

PMID: 28614065 [PubMed - as supplied by publisher]

The incremental cost of Incompatible Living Donor Kidney Transplant: A National Cohort Analysis.

Thu, 06/15/2017 - 15:45

The incremental cost of Incompatible Living Donor Kidney Transplant: A National Cohort Analysis.

Am J Transplant. 2017 Jun 14;:

Authors: Axelrod D, Lentine KL, Schnitzler MA, Luo X, Xiao H, Orandi BJ, Massie A, Garonzik-Wang J, Stegall MD, Jordan SC, Oberholzer J, Dunn TB, Ratner LE, Kapur S, Pelletier RP, Roberts JP, Melcher ML, Singh P, Sudan DL, Posner MP, El-Amm JM, Shapiro R, Cooper M, Lipkowitz GS, Rees MA, Marsh CL, Sankari BR, Gerber DA, Nelson PW, Wellen J, Bozorgzadeh A, Gaber AO, Montgomery RA, Segev DL

Abstract
Incompatible living donor kidney transplant (ILDKT) has been established as an effective option for end stage renal disease (ESRD) patients with willing but HLA incompatible live donors, reducing mortality and improving quality of life. Depending upon antibody titer, ILDKT can require highly resource intensive procedure including intravenous immunoglobulin, plasma exchange and/or cell depleting antibody treatment as well as protocol biopsies and DSA testing. This study sought to compare the cost and Medicare reimbursement, exclusive of organ acquisition payment, for ILDKT recipients (N=926) with varying antibody titers to matched compatible transplants (N=2762) performed between 2002-2011. Data were assembled from a national cohort study of ILDKT and a unique dataset linking hospital cost accounting data, and Medicare claims. Overall, ILDKT transplants were 41% more expensive than their compatible counterparts ($151,024 vs. $106,636, p<.0001). The incremental cost varied by antibody titers: positive on Luminex assay but negative flow cytometric crossmatch 20% increase, positive flow cytometric crossmatch but negative cytotoxic crossmatch 26% increase, and positive cytotoxic crossmatch 39% increase (p<.0001 for all). ILDKT was associated with higher Medicare payments ($91,330 vs. $63,782 p<.0001), longer median length of stay (12.9 vs. 7.8 days), and greater outlier payments. In conclusion, ILDKT increases the cost of and payments for kidney transplant. This article is protected by copyright. All rights reserved.

PMID: 28613436 [PubMed - as supplied by publisher]

Donor Recipient Matching Based on Predicted Recognizable HLA Epitopes Predicts the Incidence of De Novo Donor-Specific HLA Antibodies Following Renal Transplantation.

Thu, 06/15/2017 - 15:45

Donor Recipient Matching Based on Predicted Recognizable HLA Epitopes Predicts the Incidence of De Novo Donor-Specific HLA Antibodies Following Renal Transplantation.

Am J Transplant. 2017 Jun 14;:

Authors: Lachmann N, Niemann M, Reinke P, Budde K, Schmidt D, Halleck F, Pruß A, Schönemann C, Spierings E, Staeck O

Abstract
De novo donor-specific HLA antibodies (dnDSA) are recognized as risk factor for premature allograft failure. Determinants of DSA specificity are generated via the indirect allorecognition pathway. Here, we present supportive data for the relevance of predicted indirectly recognizable HLA epitopes (PIRCHE) to predict dnDSA following kidney transplantation. A total of 2,787 consecutive kidney transplants performed 1995-2015 without preformed DSA have been analyzed. De novo DSA were detected by single antigen bead assay. HLA epitope mismatches were determined by the HLAMatchmaker and PIRCHE approach and correlated in uni- and multivariate analyses with 10-year allograft survival and incidence of dnDSA. The PIRCHE-II score moderately predicted allograft survival. However, the predictive value of elevated PIRCHE-II scores >9 for the incidence of dnDSA was statistically significant (p<0.001). In a multivariate cox regression analysis adjusted for antigen mismatch and HLAMatchmaker epitopes the PRCHE-II score could be identified as an independent risk factor for dnDSA. The PIRCHE-II score independently from the antigen mismatch and HLAMatchmaker epitopes could be revealed as having a strong predictor for dnDSA. PIRCHE may help to identify acceptable mismatches with decreased risk of dnDSA and thus improve long-term renal allograft survival. This article is protected by copyright. All rights reserved.

PMID: 28613392 [PubMed - as supplied by publisher]

Study on the association of UGT1A9 gene c.98T>C polymorphism and mycophenolic acid plasma levels in renal transplant patients.

Thu, 06/15/2017 - 15:45

Study on the association of UGT1A9 gene c.98T>C polymorphism and mycophenolic acid plasma levels in renal transplant patients.

Genet Mol Res. 2017 May 31;16(2):

Authors: Ruschel LR, Schmitt VM, Silva AB, Oliveira CSA, Flach K, d'Avila DO, Thiesen FV

Abstract
Mycophenolate mofetil (MMF) is a prodrug active only after its hydrolysis to mycophenolic acid (MPA). The UGT1A9 enzyme is of special interest since it is the main enzyme involved in the glucuronidation of MPA. Single nucleotide polymorphisms (SNPs) in the UGT1A9 gene may be responsible for individual differences in the pharmacokinetics of MMF. Expression levels and the activity of UGT1A9 may depend on the presence of some SNPs located in the gene promoter region (-2152C>T and -275T>A), as well as changes in the coding region (c.98T>C). The objective of this study was to evaluate the effect of allelic variants of the UGT1A9 c.98T>C polymorphism (rs72551330; g. 87289T>C) on MMF metabolism in renal transplant patients. MPA and MPA 7-O glucuronide (MPAG) levels were determined on plasma samples of kidney transplant patients (N = 39) by high-performance liquid chromatography using ultraviolet detection. DNA was isolated from leukocytes and stored at -20°C. The presence of SNPs was investigated using polymerase chain reaction, followed by amplicon sequencing. The analysis of the UGT1A9 c.98T>C polymorphism revealed that all study patients presented the TT genotype. Diverse MPA and MPAG plasma concentrations were detected, including therapeutic, subtherapeutic, and toxic levels. A standardized molecular method permitted identification of UGT1A9 c.98T>C polymorphism genotypes in the examined renal transplant patients. All individuals of the study group presented the same genotype (c.98TT) for that polymorphism. Thereby, no association between the c.98T>C polymorphism and MPA and MPAG plasma levels could be evaluated, despite different levels of these compounds being observed.

PMID: 28613375 [PubMed - in process]

Preemptive kidney transplantation: an ethical challenge for organ allocation policies.

Thu, 06/15/2017 - 15:45

Preemptive kidney transplantation: an ethical challenge for organ allocation policies.

Clin Ter. 2017 May-Jun;168(3):e192-e193

Authors: Petrini C

Abstract
Preemptive transplants are advisable in advanced stages of kidney disease. The clinical advantages of preemptive transplantation over dialysis are evident. Nevertheless, preemptive transplantations raise ethical concerns, particularly regarding the allocation of medical resources. The present article proposes some criteria for organ allocation policies regarding preemptive transplantations: criteria regarding medical benefit and justice are absolutely essential when addressing the issue of organ allocation, but other ethical values should also be taken into account. The "principle of double effect" offers useful pointers.

PMID: 28612895 [PubMed - in process]

Body mass index as a predictor of outcomes among pediatric kidney transplant recipient.

Thu, 06/15/2017 - 15:45
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Body mass index as a predictor of outcomes among pediatric kidney transplant recipient.

Pediatr Transplant. 2017 Jun 13;:

Authors: Dick AAS, Hansen RN, Montenovo MI, Healey PJ, Smith JM

Abstract
Controversies exist regarding the impact of obesity on patients undergoing kidney transplantation. We sought to estimate the association between BMI and patient outcomes (survival and graft function) among pediatric kidney transplant patients in the USA. We conducted a retrospective analysis of the United Network for Organ Sharing database (1987-2013), which revealed 13 014 pediatric patients (<18 years old) who underwent primary kidney transplantation. Patients were stratified into five BMI categories established by the World Health Organizations according to their Z score, which is based on age, gender and BMI. The -2, 0, and +2 categories were collapsed and served as the reference group, while the -3 (thin) and +3 (obese) categories were evaluated for differences in graft and patient survival. The survival rates between these categories were compared using the Kaplan-Meier estimator. Cox proportional hazards models were constructed to adjust for recipient and donor characteristics to estimate the risk of graft loss and mortality associated with BMI. Logistic regression models were estimated to evaluate whether there was an association between BMI and DGF. There were no differences in overall patient (P=.1655) or graft (P=.1688) survival between the severely thin, normal, and obese patients. Adjusted models also revealed no statistically significant differences in graft or patient survival. There were no differences in the odds of DGF (both unadjusted and adjusted) among the three groups. The prevalence of obesity is increasing among children who present for kidney transplant in the USA. In this national study of pediatric kidney transplant recipients, there was no difference in graft or patient survival and no differences in rates of DGF among obese children compared to normal and underweight children undergoing kidney transplantation.

PMID: 28612381 [PubMed - as supplied by publisher]

Analysis of Local versus Imported Expanded Criteria Donor (ECD) Kidneys: A Single Center Experience with 497 ECD Kidney Transplants.

Thu, 06/15/2017 - 15:45
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Analysis of Local versus Imported Expanded Criteria Donor (ECD) Kidneys: A Single Center Experience with 497 ECD Kidney Transplants.

Clin Transplant. 2017 Jun 14;:

Authors: Khan MA, El-Hennawy H, Farney AC, Rogers J, Orlando G, Reeves-Daniel A, Palanisamy A, Gautreaux M, Iskandar S, Doares W, Kaczmorski S, Stratta RJ

Abstract
The value of importing expanded criteria donor (ECD) kidneys is uncertain.
METHODS: We retrospectively reviewed our single center experience with ECD kidney transplants (KT).
RESULTS: Over 12.8 years, we performed 497 ECD KTs including 247 local and 250 imported from other donor service areas. The import ECD group had more donors (16% vs 9%) ≥ age 70, more zero HLA-mismatches (14% vs 2%), more KTs with a cold ischemia time >30 hours (46% vs 19%), and fewer kidneys managed with pump preservation (78% vs 92%, all p ≤ 0.05) compared to the local ECD group. Mean KDPIs were 80% import vs 84% local. With a mean follow-up of 55 months, actual patient and graft survival rates were 71% and 58% in import vs 76% and 58% in local ECD KTs, respectively. Death-censored graft survival rates were 70% in import vs 69% in local ECD KTs. Delayed graft function occurred in 28% import vs 23% local ECD KTs (p=NS) whereas the incidence of primary nonfunction was slightly higher with import ECD kidneys (4.8% vs 2.4%, p=0.23).
CONCLUSIONS: Mid-term outcomes are remarkably similar for import vs local ECD KTs, suggesting that broader sharing of ECD kidneys may improve utilization without compromising outcomes. This article is protected by copyright. All rights reserved.

PMID: 28612360 [PubMed - as supplied by publisher]

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