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Apparent mineralocorticoid excess and the long term treatment of genetic hypertension.

Sat, 06/24/2017 - 12:45
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Apparent mineralocorticoid excess and the long term treatment of genetic hypertension.

J Steroid Biochem Mol Biol. 2017 Jan;165(Pt A):145-150

Authors: Razzaghy-Azar M, Yau M, Khattab A, New MI

Abstract
Apparent mineralocorticoid excess (AME) is a genetic disorder causing severe hypertension, hypokalemia, and hyporeninemic hypoaldosteronism owing to deficient 11 beta-hydroxysteroid dehydrogenase type-2 (11βHSD2) enzyme activity. The 11βHSD2 enzyme confers mineralocorticoid receptor specificity for aldosterone by converting cortisol to its inactive metabolite, cortisone and inactivating the cortisol-mineralocorticoid receptor complex. The 20year follow-up of a consanguineous Iranian family with three sibs affected with AME shows the successes and pitfalls of medical therapy with spironolactone. The three sibs, (female, male, female) were diagnosed at the ages of 14, 11, and 4 years, respectively. At diagnosis, hypertensive retinopathy and left ventricular hypertrophy were present in the eldest female and retinopathy was noted in the male sib. Spironolactone treatment resulted in decreased blood pressure and rise in serum potassium levels. The older female, age 36, developed reduced left ventricular function with mitral and tricuspid regurgitation and renal failure after her second pregnancy. She was treated with renal transplantation resulting in cure of AME with decreased blood pressure and weaning from antihypertensives. Her younger sibs, age 34 and 26, do not have end organ damage. Early and vigilant treatment improves morbidity in patients with AME. Mineralocorticoid receptor antagonists normalize blood pressure, correct hypokalemia and reduce hypertensive end-organ damage in patients with AME. Low dose dexamethasone can be considered, though the response may be variable. Future directions of therapy include selective mineralocorticoid antagonists.

PMID: 26892095 [PubMed - indexed for MEDLINE]

Selective CD28 blockade results in superior inhibition of donor-specific T follicular helper cell and antibody responses relative to CTLA-4-Ig.

Thu, 06/22/2017 - 12:45
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Selective CD28 blockade results in superior inhibition of donor-specific T follicular helper cell and antibody responses relative to CTLA-4-Ig.

Am J Transplant. 2017 Jun 21;:

Authors: Badell IR, La Muraglia GM, Liu D, Wagener ME, Ding G, Ford ML

Abstract
Donor-specific antibodies (DSA) are a barrier to improved long-term outcomes following kidney transplantation. Costimulation blockade with CTLA-4-Ig has shown promise as a potential therapeutic strategy to control DSA. T follicular helper (Tfh) cells, a subset of CD4(+) T cells required for optimum antibody production, are reliant on the CD28 costimulatory pathway. We have previously shown that selective CD28 blockade leads to superior allograft survival through improved control of CD8(+) T cells relative to CTLA-4-Ig, but the impact of CD28-specific blockade on CD4(+) Tfh cells is unknown. Thus, we identified and characterized donor-reactive Tfh cells in a murine skin transplant model, and then utilized this model to evaluate the impact of selective CD28 blockade with an anti-CD28 domain antibody (dAb) on the donor-specific Tfh-mediated immune response. We observed that the anti-CD28 dAb led to superior inhibition of donor-reactive CXCR5(+) PD-1(hi) Tfh and CD95(+) GL7(+) germinal center B cells, and DSA formation as compared to CTLA-4-Ig. Interestingly, donor-reactive Tfh cells differentially upregulated CTLA-4 expression, suggesting an important role for CTLA-4 in mediating the superior inhibition observed with the anti-CD28 dAb. Therefore, selective CD28 blockade as a novel approach to control Tfh cell responses and prevent DSA after kidney transplantation warrants further study. This article is protected by copyright. All rights reserved.

PMID: 28637095 [PubMed - as supplied by publisher]

Intra-abdominal cooling system limits ischemia-reperfusion injury during robot-assisted renal transplantation.

Thu, 06/22/2017 - 12:45
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Intra-abdominal cooling system limits ischemia-reperfusion injury during robot-assisted renal transplantation.

Am J Transplant. 2017 Jun 21;:

Authors: Meier RPH, Piller V, Hagen ME, Joliat C, Buchs JB, Nastasi A, Ruttimann R, Buchs NC, Moll S, Vallée JP, Lazeyras F, Morel P, Bühler L

Abstract
Robot-assisted kidney transplantation is feasible; however, concerns have been raised about possible increases in warm ischemia times. We describe a novel intra-abdominal cooling system to continuously cool the kidney during the procedure. Porcine kidneys were procured by standard open technique. Groups were as follow: Robotic renal transplantation with (n=11) and without (n=6) continuous intra-abdominal cooling and conventional open technique with intermittent 4°C saline cooling (n=6). Renal cortex temperature, magnetic resonance imaging and histology were analyzed. Robotic renal transplantation required a longer operative time, either with or without the cooling system, compared to the open approach (70.4±17.7 min and 74.0±21.5 min vs. 49.4±12.4 min, p-values<0.05). The temperature was lower in the robotic group with cooling system compared to the open approach group (6.5±3.1°C vs. 22.5±6.5°C; p=0.002) or compared to the robotic group without the cooling system (28.7±3.3°C; p=0.133). MRI parenchymal heterogeneities and histologic ischemia-reperfusion lesions were more severe in the robotic group without cooling than in the cooled (open and robotic) groups. Robot-assisted kidney transplantation prolongs the warm ischemia time of the donor kidney. We developed a novel intra-abdominal cooling system that suppresses the non-controlled rewarming of donor kidneys during the transplant procedure and prevents ischemia-reperfusion injuries. This article is protected by copyright. All rights reserved.

PMID: 28637093 [PubMed - as supplied by publisher]

[Clinical Course of an Early Childhood-Onset Granulomatosis with Polyangiitis].

Thu, 06/22/2017 - 12:45
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[Clinical Course of an Early Childhood-Onset Granulomatosis with Polyangiitis].

Dtsch Med Wochenschr. 2017 Jun;142(12):904-908

Authors: Krasselt M, Pierer M, Amann K, Bachmann A, Lindner TH

Abstract
History A 26-year-old male patient presented with an eight-week history of unspecific symptoms such as weight loss and fever. Besides, he also suffered from haemoptysis, cough, and arthralgia. Since the age of twelve years, the patient has been treated for Wegner's granulomatosis. At the age of 20 years he received a kidney transplant which failed only four years later. Investigations The relapse we clinically suspected was confirmed by CT scan showing bilateral pulmonary manifestations. Moreover, we found highly positive antibodies against proteinase 3. Treatment and course After an induction therapy using Glucocorticoids and Rituximab, accompanied by plasmapheresis, the patient's clinical condition showed a marked improvement. We were able to discharge him continuing the treatment in an outpatient setting. Conclusion Childhood-onset GPA is a life-threatening disease and often characterized by recurring relapses as well as a significantly reduced quality of life for the patient.

PMID: 28637076 [PubMed - in process]

Comparison of cyclophosphamide-thalidomide-dexamethasone to bortezomib-cyclophosphamide-dexamethasone as induction therapy for multiple myeloma patients in Brazil.

Thu, 06/22/2017 - 12:45
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Comparison of cyclophosphamide-thalidomide-dexamethasone to bortezomib-cyclophosphamide-dexamethasone as induction therapy for multiple myeloma patients in Brazil.

Hematol Oncol Stem Cell Ther. 2017 Jun 15;:

Authors: Vigolo S, Zuckermann J, Bittencourt RI, Silla L, Pilger DA

Abstract
OBJECTIVE/BACKGROUND: Chemotherapy followed by autologous hematopoietic stem cell transplantation (HSCT) remains the standard treatment for multiple myeloma (MM). Thalidomide or bortezomib may be combined with cyclophosphamide and dexamethasone, in what are known as the CTD and VCD protocols, respectively. The objective of this study was to evaluate the clinical characteristics and response rates obtained with CTD and VCD, observing whether the inclusion of bortezomib to treat MM patients in Brazil increases therapeutic efficiency.
METHODS: Forty-three MM patients treated with induction protocols CTD and VCD between January 2010 and March 2015 were included. The parameters analyzed were staging, frequency of comorbidities prior to treatment, response rates obtained at each induction cycle, progression-free survival, and overall survival of patients.
RESULTS: Very good partial response and complete response obtained with the VCD protocol were superior, compared with the CTD treatment. The presence of comorbidities was similar in the two groups, except kidney failure, which prevailed in the VCD group. Also, 78.3% and 48.3% of patients treated with the VCD and CTD protocols underwent autologous HSCT, respectively. In patients given the VCD protocol, 45.5% had complete response before autologous HSCT. Among those given CTD, this number was only 7.1% (p=0.023). Disease progression after autologous HSCT did not differ between the two groups.
CONCLUSION: VCD afforded better responses than the CTD protocol, and improved patient condition before autologous HSCT. However, more studies are necessary including more patients and addressing various clinical conditions, besides the analysis of cost-effectiveness of these treatments.

PMID: 28636891 [PubMed - as supplied by publisher]

Babesiosis: An unusual cause of sepsis after kidney transplantation and review of the literature.

Thu, 06/22/2017 - 12:45
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Babesiosis: An unusual cause of sepsis after kidney transplantation and review of the literature.

Transpl Infect Dis. 2017 Jun 21;:

Authors: Ather I, Pourafshar N, Schain D, Gupte A, Casey MJ

Abstract
We report a unique case of babesiosis presenting as sepsis after kidney transplantation. A 70-year-old female kidney transplant recipient presented with fever, hemolytic anemia, and acute kidney injury, and met three of four systemic inflammatory response syndrome (SIRS) criteria. Serology was positive for Babesia microti, confirmed by polymerase chain reaction. The patient was treated with atovaquone and azithromycin and made a full recovery. Reports of babesiosis after solid organ transplantation are rare, with only four prior cases reported in the literature. We report the first case of babesiosis, to our knowledge, presenting as sepsis that was successfully treated after solid organ transplantation. This article is protected by copyright. All rights reserved.

PMID: 28636757 [PubMed - as supplied by publisher]

Measurement properties of patient-reported outcome measures (PROMs) used in adult patients with chronic kidney disease: A systematic review.

Thu, 06/22/2017 - 12:45
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Measurement properties of patient-reported outcome measures (PROMs) used in adult patients with chronic kidney disease: A systematic review.

PLoS One. 2017;12(6):e0179733

Authors: Aiyegbusi OL, Kyte D, Cockwell P, Marshall T, Gheorghe A, Keeley T, Slade A, Calvert M

Abstract
BACKGROUND: Patient-reported outcome measures (PROMs) can provide valuable information which may assist with the care of patients with chronic kidney disease (CKD). However, given the large number of measures available, it is unclear which PROMs are suitable for use in research or clinical practice. To address this we comprehensively evaluated studies that assessed the measurement properties of PROMs in adults with CKD.
METHODS: Four databases were searched; reference list and citation searching of included studies was also conducted. The COnsensus-based Standards for the selection of health Measurement INstruments (COSMIN) checklist was used to appraise the methodological quality of the included studies and to inform a best evidence synthesis for each PROM.
RESULTS: The search strategy retrieved 3,702 titles/abstracts. After 288 duplicates were removed, 3,414 abstracts were screened and 71 full-text articles were retrieved for further review. Of these, 24 full-text articles were excluded as they did not meet the eligibility criteria. Following reference list and citation searching, 19 articles were retrieved bringing the total number of papers included in the final analysis to 66. There was strong evidence supporting internal consistency and moderate evidence supporting construct validity for the Kidney Disease Quality of Life-36 (KDQOL-36) in pre-dialysis patients. In the dialysis population, the KDQOL-Short Form (KDQOL-SF) had strong evidence for internal consistency and structural validity and moderate evidence for test-retest reliability and construct validity while the KDQOL-36 had moderate evidence of internal consistency, test-retest reliability and construct validity. The End Stage Renal Disease-Symptom Checklist Transplantation Module (ESRD-SCLTM) demonstrated strong evidence for internal consistency and moderate evidence for test-retest reliability, structural and construct validity in renal transplant recipients.
CONCLUSIONS: We suggest considering the KDQOL-36 for use in pre-dialysis patients; the KDQOL-SF or KDQOL-36 for dialysis patients and the ESRD-SCLTM for use in transplant recipients. However, further research is required to evaluate the measurement error, structural validity, responsiveness and patient acceptability of PROMs used in CKD.

PMID: 28636678 [PubMed - in process]

Plasma cell neoplasia after kidney transplantation: French cohort series and review of the literature.

Thu, 06/22/2017 - 12:45
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Plasma cell neoplasia after kidney transplantation: French cohort series and review of the literature.

PLoS One. 2017;12(6):e0179406

Authors: Kormann R, François H, Moles T, Dantal J, Kamar N, Moreau K, Bachelet T, Heng AE, Garstka A, Colosio C, Ducloux D, Sayegh J, Savenkoff B, Viglietti D, Sberro R, Rondeau E, Peltier J

Abstract
Although post-transplant lymphoproliferative disorder (PTLD) is the second most common type of cancer in kidney transplantation (KT), plasma cell neoplasia (PCN) occurs only rarely after KT, and little is known about its characteristics and evolution. We included twenty-two cases of post-transplant PCN occurring between 1991 and 2013. These included 12 symptomatic multiple myeloma, eight indolent myeloma and two plasmacytomas. The median age at diagnosis was 56.5 years and the median onset after transplantation was 66.7 months (2-252). Four of the eight indolent myelomas evolved into symptomatic myeloma after a median time of 33 months (6-72). PCN-related kidney graft dysfunction was observed in nine patients, including six cast nephropathies, two light chain deposition disease and one amyloidosis. Serum creatinine was higher at the time of PCN diagnosis than before, increasing from 135.7 (±71.6) to 195.9 (±123.7) μmol/l (p = 0.008). Following transplantation, the annual rate of bacterial infections was significantly higher after the diagnosis of PCN, increasing from 0.16 (±0.37) to 1.09 (±1.30) (p = 0.0005). No difference was found regarding viral infections before and after PCN. Acute rejection risk was decreased after the diagnosis of PCN (36% before versus 0% after, p = 0.004), suggesting a decreased allogeneic response. Thirteen patients (59%) died, including twelve directly related to the hematologic disease. Median graft and patient survival was 31.7 and 49.4 months, respectively. PCN after KT occurs in younger patients compared to the general population, shares the same clinical characteristics, but is associated with frequent bacterial infections and relapses of the hematologic disease that severely impact the survival of grafts and patients.

PMID: 28636627 [PubMed - in process]

The experience of waiting for a kidney transplant: A qualitative study.

Thu, 06/22/2017 - 12:45
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The experience of waiting for a kidney transplant: A qualitative study.

J Ren Care. 2017 Jun 21;:

Authors: Burns T, Fernandez R, Stephens M

Abstract
BACKGROUND: In Australia over 1100 people are living on dialysis while waiting for a kidney transplant from a deceased donor. Worldwide there are an estimated 170,000 people who wait an average of three years before an organ becomes available.
OBJECTIVE: To provide an understanding of the lived experience of people waiting on dialysis for a kidney transplant from a deceased donor.
APPROACH: A qualitative descriptive research design was used. Participants were recruited from a large metropolitan hospital. Two focus groups were conducted with six participants ranging in age from 29-63 years, with dialysis experience of 10-72 months. Data saturation was achieved and thematic analysis was used to interpret the data providing a descriptive account of the experience of waiting for a kidney transplant.
FINDINGS: Waiting for a kidney transplant takes place in the context of living on dialysis. Four main themes were identified: living on dialysis is physically and mentally demanding; living with uncertainty; altered relationship dynamics; and feelings towards the deceased donor.
CONCLUSIONS: This study provides a descriptive summary of what it is like to live on dialysis while waiting for a kidney transplant from a deceased donor from the perspective of the person waiting. People are burdened by; uncertainty; the experience of the dialysis therapy; and the thought of the human cost of transplantation. These findings suggest that this cohort may benefit from strategies to relieve uncertainty such as effective communication from the treating team and peer support from the dialysis community.

PMID: 28636137 [PubMed - as supplied by publisher]

Optimizing outcomes in pancreas transplantation: Impact of organ preservation time.

Thu, 06/22/2017 - 12:45
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Optimizing outcomes in pancreas transplantation: Impact of organ preservation time.

Clin Transplant. 2017 Jun 21;:

Authors: Rudolph EN, Dunn TB, Sutherland DER, Kandaswamy R, Finger EB

Abstract
Recent changes to pancreas graft allocation policy have increased the number of organs available for regional and distant sharing, which results in a corresponding increase in preservation time. We sought to systematically assess the impact of cold ischemia time (CIT) on outcomes posttransplant. A retrospective review of 1,253 pancreas transplants performed at a single transplant center was performed to correlate CIT to transplant outcomes. The rate of technical failure (TF) increased with 20+ hours of CIT, with a 2.7- to 6.2-fold increased rate of TF for pancreas after kidney (PAK), simultaneous pancreas and kidney (SPK), and pancreas transplants overall. Long-term graft survival was best with <12 hours of CIT; graft failure increased 1.2- to 1.4-fold with 12-24 hours of CIT and 2.2-fold with 24+ hours. CIT had less influence on the pancreas transplant alone (PTA) category than either SPK or PAK, and had markedly more influence on grafts from older (age >25 years) and overweight (BMI >25) donors. In the final analysis, grafts with <12 hours of CIT performed the best overall, and strategies that reduce CIT (such as early allocation, pre-recovery crossmatching, and chartered flights for organs) should be considered whenever possible. This article is protected by copyright. All rights reserved.

PMID: 28636074 [PubMed - as supplied by publisher]

The Application of Heptamethine Cyanine Dye DZ-1 and Indocyanine Green for Imaging and Targeting in Xenograft Models of Hepatocellular Carcinoma.

Thu, 06/22/2017 - 12:45
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The Application of Heptamethine Cyanine Dye DZ-1 and Indocyanine Green for Imaging and Targeting in Xenograft Models of Hepatocellular Carcinoma.

Int J Mol Sci. 2017 Jun 21;18(6):

Authors: Zhang C, Zhao Y, Zhang H, Chen X, Zhao N, Tan D, Zhang H, Shi C

Abstract
Near infrared fluorescence (NIRF) imaging has strong potential for widespread use in noninvasive tumor imaging. Indocyanine green (ICG) is the only Food and Drug Administration (FDA) -approved NIRF dye for clinical diagnosis; however, it is unstable and poorly targets tumors. DZ-1 is a novel heptamethine cyanine NIRF dye, suitable for imaging and tumor targeting. Here, we compared the fluorescence intensity and metabolism of DZ-1 and ICG. Additionally, we assayed their specificities and abilities to target tumor cells, using cultured hepatocellular carcinoma (HCC) cell lines, a nude mouse subcutaneous xenograft model of liver cancer, and a rabbit orthotopic transplantation model. We found that DZ-1 accumulates in tumor tissue and specifically recognizes HCC in subcutaneous and orthotopic models. The NIRF intensity of DZ-1 was one order of magnitude stronger than that of ICG, and DZ-1 showed excellent intraoperative tumor targeting in the rabbit model. Importantly, ICG accumulated at tumor sites, as well as in the liver and kidney. Furthermore, DZ-1 analog-gemcitabine conjugate (NIRG) exhibited similar tumor-specific targeting and imaging properties, including inhibition of tumor growth, in HCC patient-derived xenograft (PDX) mice. DZ-1 and NIRG demonstrated superior tumor-targeting specificity, compared to ICG. We show that DZ-1 is an effective molecular probe for specific imaging, targeting, and therapy in HCC.

PMID: 28635650 [PubMed - in process]

Longitudinal study on the use of dried blood spots for home monitoring in children after kidney transplantation.

Thu, 06/22/2017 - 12:45
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Longitudinal study on the use of dried blood spots for home monitoring in children after kidney transplantation.

Pediatr Transplant. 2017 Jun 20;:

Authors: Al-Uzri A, Freeman KA, Wade J, Clark K, Bleyle LA, Munar M, Koop DR

Abstract
The use of DBSs for home monitoring has been limited due to unsatisfactory blood sampling and analytical difficulties. The aim of this longitudinal feasibility trial was to assess the utility of DBS to monitor TAC and Cr at home in transplant recipients. A total of 30 participants (2-21 years, mean±SD, 13.6±5.4 year) were enrolled over 12 months. Eighteen were males. Monthly DBS samples were obtained at home and mailed to the central laboratory for analysis of TAC and Cr. Nineteen patients completed the study, and 216 cards were received in the laboratory from a total of 279 cards expected, with 416/519 (80%) blood spots being suitable for analysis. We found a high correlation between blood TAC and Cr levels by DBS and the clinical laboratory, R(2) =.81 and .95, respectively. Fifteen parents and 15 youth completed measures of satisfaction with and preference for DBS testing. All but one parent/caregiver and youth reported satisfaction and preference for this method of testing over laboratory blood draws. We conclude that home DBS monitoring is a feasible method to monitor TAC and Cr in pediatric transplant recipients.

PMID: 28635157 [PubMed - as supplied by publisher]

Outcomes of Kidney Donors over 60 Years Old: A Single-Center Cohort Study.

Thu, 06/22/2017 - 12:45
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Outcomes of Kidney Donors over 60 Years Old: A Single-Center Cohort Study.

World J Surg. 2017 Jun 20;:

Authors: Gero D, Dib F, Matter M, Pascual M, Venetz JP, Demartines N, Melloul E

Abstract
AIM: To evaluate outcomes and post-donation kidney function of older living kidney donors (LKD).
METHODS: Retrospective analysis of prospective database including all consecutive LKD undergoing laparoscopic nephrectomy in a single center (09/1998-12/2013). LKD aged ≥60 years were compared to younger LKD. Renal function assessed by creatinine levels and estimated glomerular filtration rates (eGFR). Surgical complications classified according to the Clavien-Dindo classification. Bivariate and multivariate analyses using linear mixed effect models were performed to determine factors (age, gender, hypertension status, BMI, choice of better functioning kidney for donation) that might impinge on renal function after donation.
RESULTS: 213 LKD were identified: 49 older (median age: 66 years, range: 60-79) and 164 younger (median age: 46, range: 25-59). Mean operative time (149 vs. 152 min, p = 0.69), conversion to laparotomy (n = 1 vs. 3, p = 0.92), grade III-IV complications (n = 4 vs. 2, p = 0.36) were similar. Older had more grade I-II complications (n = 18 vs. 4, p < 0.001). Despite similar pre-donation eGFR (80 vs. 84 ml/min/1.73 m(2)), older donors presented significantly lower eGFR during inpatient period (46 vs. 51 ml/min/1.73 m(2), p = 0.0003), at 1 month (51 vs. 58 ml/min/1.73 m(2), p = 0.002) and at 1 year (54 vs. 62 ml/min/1.73 m(2), p = 0.001). Multivariate analysis adjusted to gender, hypertension status, BMI and choice of better functioning kidney for donation showed that at 1 year, age ≥60 affected renal function by a coefficient of 0.91 (p < 0.001).
CONCLUSION: Despite renal function improvement after discharge, LKD ≥ 60 years presented lower eGFR than younger at one year and had more grade I-II surgical complications.

PMID: 28634839 [PubMed - as supplied by publisher]

The effect of desensitization therapy in kidney transplantation.

Thu, 06/22/2017 - 12:45
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The effect of desensitization therapy in kidney transplantation.

Clin Exp Nephrol. 2017 Jun 20;:

Authors: Kim YC, Yu MY, Lee JP, Lee H, Min SI, Ha J, Kim YS

Abstract
BACKGROUND: Desensitization therapy may enable the patient to get allograft in sensitized recipient or solve the organ shortage in ABO-incompatible relationship in kidney transplantation (KT). However, the graft outcome and morbidity remains unclear.
METHODS: We retrospectively analyzed 845 KT patients from January 2010 to February 2016 at Seoul National University Hospital. The patients were divided into three groups as follows: HLA-incompatible (HLAi) group, ABO-incompatible (ABOi) group, and control group. The HLAi group comprised patients who received desensitization therapy due to the presence of donor-specific antibodies (DSAs) or high panel reactive antibodies (PRAs). The ABOi group is defined as those undergoing preoperative desensitization therapy for anti-ABO antibodies.
RESULTS: Of the total of 845 recipients, 48 (5.6%) were HLAi KTs and 71 (13.9%) were ABOi KTs, respectively. Pre-emptive KT is done more frequently in ABOi group, therefore, they had shorter dialysis duration than the others. HLAi recipients had a higher proportion of women than the ABOi group and a higher proportion of re-transplantation. During the 38.4 (0.4-76.9) months of follow-up, there were more acute antibody-mediated rejections (AAMRs) in the HLAi (6.7%) and ABOi (8.5%) groups than in the control group (1.9%) (P = 0.001). However, there was no difference in graft survival, patient survival, and annual allograft among three groups.
CONCLUSIONS: Despite the higher incidence of AAMRs, HLAi and ABOi KTs showed a favorable graft and patient outcome after desensitization therapy.

PMID: 28634772 [PubMed - as supplied by publisher]

Standardized and weighted time-dependent receiver operating characteristic curves to evaluate the intrinsic prognostic capacities of a marker by taking into account confounding factors.

Thu, 06/22/2017 - 12:45
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Standardized and weighted time-dependent receiver operating characteristic curves to evaluate the intrinsic prognostic capacities of a marker by taking into account confounding factors.

Stat Methods Med Res. 2017 Jan 01;:962280217702416

Authors: Le Borgne F, Combescure C, Gillaizeau F, Giral M, Chapal M, Giraudeau B, Foucher Y

Abstract
Time-dependent receiver operating characteristic curves allow to evaluate the capacity of a marker to discriminate between subjects who experience the event up to a given prognostic time from those who are free of this event. In this article, we propose an inverse probability weighting estimator of a standardized and weighted time-dependent receiver operating characteristic curve. This estimator provides a measure of the prognostic capacities by taking into account potential confounding factors. We illustrate the robustness of the estimator by a simulation-based study and its usefulness by two applications in kidney transplantation.

PMID: 28633603 [PubMed - as supplied by publisher]

Functional principal component analysis of glomerular filtration rate curves after kidney transplant.

Thu, 06/22/2017 - 12:45
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Functional principal component analysis of glomerular filtration rate curves after kidney transplant.

Stat Methods Med Res. 2017 Jan 01;:962280217712088

Authors: Dong JJ, Wang L, Gill J, Cao J

Abstract
This article is motivated by some longitudinal clinical data of kidney transplant recipients, where kidney function progression is recorded as the estimated glomerular filtration rates at multiple time points post kidney transplantation. We propose to use the functional principal component analysis method to explore the major source of variations of glomerular filtration rate curves. We find that the estimated functional principal component scores can be used to cluster glomerular filtration rate curves. Ordering functional principal component scores can detect abnormal glomerular filtration rate curves. Finally, functional principal component analysis can effectively estimate missing glomerular filtration rate values and predict future glomerular filtration rate values.

PMID: 28633602 [PubMed - as supplied by publisher]

Single-Nephron Glomerular Filtration Rate in Healthy Adults.

Thu, 06/22/2017 - 12:45
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Single-Nephron Glomerular Filtration Rate in Healthy Adults.

N Engl J Med. 2017 06 15;376(24):2349-2357

Authors: Denic A, Mathew J, Lerman LO, Lieske JC, Larson JJ, Alexander MP, Poggio E, Glassock RJ, Rule AD

Abstract
BACKGROUND: The glomerular filtration rate (GFR) assesses the function of all nephrons, and the single-nephron GFR assesses the function of individual nephrons. How the single-nephron GFR relates to demographic and clinical characteristics and kidney-biopsy findings in humans is unknown.
METHODS: We identified 1388 living kidney donors at the Mayo Clinic and the Cleveland Clinic who underwent a computed tomographic (CT) scan of the kidney with the use of contrast material and an iothalamate-based measurement of the GFR during donor evaluation and who underwent a kidney biopsy at donation. The mean single-nephron GFR was calculated as the GFR divided by the number of nephrons (calculated as the cortical volume of both kidneys as assessed on CT times the biopsy-determined glomerular density). Demographic and clinical characteristics and biopsy findings were correlated with the single-nephron GFR.
RESULTS: A total of 58% of the donors were women, and the mean (±SD) age of the donors was 44±12 years. The mean GFR was 115±24 ml per minute, the mean number of nephrons was 860,000±370,000 per kidney, and the mean single-nephron GFR was 80±40 nl per minute. The single-nephron GFR did not vary significantly according to age (among donors <70 years of age), sex, or height (among donors ≤190 cm tall). A higher single-nephron GFR was independently associated with larger nephrons on biopsy and more glomerulosclerosis and arteriosclerosis than would be expected for age. A higher single-nephron GFR was associated with a height of more than 190 cm, obesity, and a family history of end-stage renal disease.
CONCLUSIONS: Among healthy adult kidney donors, the single-nephron GFR was fairly constant with regard to age, sex, and height (if ≤190 cm). A higher single-nephron GFR was associated with certain risk factors for chronic kidney disease and certain kidney-biopsy findings. (Funded by the National Institute of Diabetes and Digestive and Kidney Diseases.).

PMID: 28614683 [PubMed - indexed for MEDLINE]

Blood pressure-independent renoprotection in diabetic rats treated with AT1 receptor-neprilysin inhibition compared with AT1 receptor blockade alone.

Thu, 06/22/2017 - 12:45
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Blood pressure-independent renoprotection in diabetic rats treated with AT1 receptor-neprilysin inhibition compared with AT1 receptor blockade alone.

Clin Sci (Lond). 2016 Jul 01;130(14):1209-20

Authors: Roksnoer LC, van Veghel R, van Groningen MC, de Vries R, Garrelds IM, Bhaggoe UM, van Gool JM, Friesema EC, Leijten FP, Hoorn EJ, Danser AH, Batenburg WW

Abstract
ARNI [dual AT1 (angiotensin II type 1) receptor-neprilysin inhibition] exerts beneficial effects on blood pressure and kidney function in heart failure, compared with ARB (AT1 receptor blockade) alone. We hypothesized that ARNI improves cardiac and kidney parameters in diabetic TGR(mREN2)27 rats, an angiotensin II-dependent hypertension model. Rats were made diabetic with streptozotocin for 5 or 12 weeks. In the final 3 weeks, rats were treated with vehicle, irbesartan (ARB) or irbesartan+thiorphan (ARNI). Blood pressure, measured by telemetry in the 5-week group, was lowered identically by ARB and ARNI. The heart weight/tibia length ratio in 12-week diabetic animals was lower after ARNI compared with after ARB. Proteinuria and albuminuria were observed from 8 weeks of diabetes onwards. ARNI reduced proteinuria more strongly than ARB, and a similar trend was seen for albuminuria. Kidneys of ARNI-treated animals showed less severe segmental glomerulosclerosis than those of ARB-treated animals. After 12 weeks, no differences between ARNI- and ARB-treated animals were found regarding diuresis, natriuresis, plasma endothelin-1, vascular reactivity (acetylcholine response) or kidney sodium transporters. Only ARNI-treated rats displayed endothelin type B receptor-mediated vasodilation. In conclusion, ARNI reduces proteinuria, glomerulosclerosis and heart weight in diabetic TGR(mREN2)27 rats more strongly than does ARB, and this occurs independently of blood pressure.

PMID: 27129187 [PubMed - indexed for MEDLINE]

Survival of patients with cancer starting chronic dialysis: data from kidney and cancer registries in Lower Normandy.

Wed, 06/21/2017 - 21:45

Survival of patients with cancer starting chronic dialysis: data from kidney and cancer registries in Lower Normandy.

Nephrology (Carlton). 2017 Jun 20;:

Authors: Béchade C, Dejardin O, Bara S, Bouvier V, Guizard AV, De Mil R, Troussard X, Launoy G, Lobbedez T

Abstract
AIM: Cancer and chronic kidney disease are known to be associated. The way in which a history of cancer can influence outcome in dialysis is not well described. This work aimed to evaluate survival of cancer patients starting chronic dialysis after their diagnosis of cancer.
METHODS: We merged data from cancer registries and a dialysis registry, and explored patients' charts.
RESULTS: Between January 2001 and December 2008, 74 patients with incident cancer in the two-counties-study-area (Calvados and Manche) started chronic dialysis after their diagnosis of cancer. Survival of these incident dialysis patients with a previous diagnosis of cancer was respectively 80.9% (confidence interval 69.9; 88.2) and 68.3% (confidence interval 56.3%; 77.7%) at one and two years. Only 29 of the 74 patients (39.2%) were still alive at the end of the observation period; median participation time was 2.8 years (1(st) and 3(rd) quartiles: 1.3-4.4). Survival of patients with cancer was not different to that of non-cancer dialysis patients matched for age and sex, except in patients with haematological malignancies who had a poorer outcome. In a multivariate stratified Cox model, the history of cancer before dialysis start was not associated with death, after adjustment on diabetes.
CONCLUSION: In our study, survival in dialysis was not different among patients with a history of cancer compared to matched patients without malignancy. We can hypothesize that only some selected patients with cancer have access to dialysis. Studies in ESRD patients with cancer should be performed to evaluate access to dialysis in that population.

PMID: 28633195 [PubMed - as supplied by publisher]

The prevalence and correlates of low sexual functioning in women on hemodialysis: A multinational, cross-sectional study.

Wed, 06/21/2017 - 21:45

The prevalence and correlates of low sexual functioning in women on hemodialysis: A multinational, cross-sectional study.

PLoS One. 2017;12(6):e0179511

Authors: Saglimbene V, Natale P, Palmer S, Scardapane M, Craig JC, Ruospo M, Gargano L, Lucisano G, Török M, Celia E, Gelfman R, Bednarek-Skublewska A, Dulawa J, Stroumza P, Leal M, Del Castillo D, Murgo AM, Schon S, Wollheim C, Hegbrant J, Strippoli GFM

Abstract
Sexual dysfunction may affect 80% of women in hemodialysis. However the specific patterns and clinical correlates of sexual functioning remain poorly described. The aim of this study was to assess prevalence and correlates of the individual domains of sexual functioning in women treated with hemodialysis. We recruited, into this multinational cross-sectional study, women treated with long-term hemodialysis (Collaborative Working Group on Depression and Sexual dysfunction in Hemodialysis study). Self-reported domains of sexual functioning were assessed by the Female Sexual Function Index, which is routinely administered within the network of dialysis patients followed by the working group. Lower scores represented lower sexual functioning. Socio-demographic and clinical correlates of each domain of sexual functioning were identified by stepwise multivariable linear regression. Sensitivity analyses were restricted to women who reported being sexually active. We found that of 1309 enrolled women, 659 (50.3%) provided complete responses to FSFI survey questions and 232 (35%) reported being sexually active. Overall, most respondents reported either no sexual activity or low sexual functioning in all measured domains (orgasm 75.1%; arousal 64.0%; lubrication 63.3%; pain 60.7%; satisfaction 60.1%; sexual desire 58.0%). Respondents who were waitlisted for a kidney transplant reported scores with higher sexual functioning, while older respondents reported scores with lower functioning. The presence of depression was associated with worse lubrication and pain scores [mean difference for depressed versus non-depressed women (95% CI) -0.42 (-0.73 to -0.11), -0.53 (-0.89 to -0.16), respectively] while women who had experienced a previous cardiovascular event reported higher pain scores [-0.77 (-1.40- to -0.13)]. In conclusion, women in hemodialysis reported scores consistent with marked low sexual functioning across a range of domains; the low functioning appeared to be associated with comorbidity.

PMID: 28632793 [PubMed - in process]

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