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Robot-assisted single port radical nephrectomy and cholecystectomy: description and technical aspects.

Thu, 10/19/2017 - 12:45
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Robot-assisted single port radical nephrectomy and cholecystectomy: description and technical aspects.

Int Braz J Urol. 2017 Oct 17;43:

Authors: Mota Filho FHA, Sávio LF, Sakata RE, Ivanovic RF, da Silva MAN, Maia R, Passerotti C

Abstract
INTRODUCTION: Robot-Assisted Single Site Radical Nephrectomy (RASS-RN) has been reported by surgeons in Europe and United States (1-3). To our best knowledge this video presents the first RASS-RN with concomitant cholecystectomy performed in Latin America.
CASE: A 66 year-old renal transplant male due to chronic renal failure presented with an incidental 1.3cm nodule in the upper pole of the right kidney. In addition, symptomatic gallbladder stones were detected.
RESULTS: Patient was placed in modified flank position. Multichannel single port device was placed using Hassan's technique through a 3cm supra-umbilical incision. Standard radical nephrectomy and cholecystectomy were made using na 8.5mm camera, two 5mm robotic arms and an assistant 5mm access. Surgery time and estimated blood loss were 208 minutes and 100mL, respectively. Patient did well and was discharged within less than 48 hours, without complications. Pathology report showed benign renomedullary tumor of interstitial cells and chronic cholecystitis.
DISCUSSION: Robotic technology improves ergonomics, gives better precision and enhances ability to approach complex surgeries. Robot-assisted Single Port aims to reduce the morbidity of multiple trocar placements while maintaining the advantages of robotic surgery (2). Limitations include the use of semi-rigid instruments providing less degree of motion and limited space leading to crash between instruments. On the other hand, it is possible to perform complex and concomitant surgeries with just one incision.
CONCLUSION: RASS-RN seems to be safe and feasible option for selected cases. Studies should be performed to better understand the results using single port technique in Urology.

PMID: 29039889 [PubMed - as supplied by publisher]

Essential role of microRNA-650 in the regulation of B-cell CLL/lymphoma 11B gene expression following transplantation: A novel mechanism behind the acute rejection of renal allografts.

Thu, 10/19/2017 - 12:45
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Essential role of microRNA-650 in the regulation of B-cell CLL/lymphoma 11B gene expression following transplantation: A novel mechanism behind the acute rejection of renal allografts.

Int J Mol Med. 2017 Oct 17;:

Authors: Jin P, Chen H, Xie J, Zhou C, Zhu X

Abstract
Kidney transplantation is an effective final therapeutic procedure for patients with end-stage kidney failure. Although advanced immunosuppressive therapy is administered following transplantation, certain patients still suffer from acute allograft rejection. MicroRNAs (miRs) have a potential diagnostic and therapeutic value for acute renal allograft rejection; however, their underlying mechanism of action is largely unknown. In the present study, an increased level of miR-650 was identified to be associated with the downregulation of B-cell CLL/lymphoma 11B (BCL11B) expression in acute renal allograft rejection. Furthermore, in vitro study using human renal glomerular endothelial cells (HRGECs) transfected with a miR-650 mimic revealed that key characteristics of acute renal allograft rejection were observed, including apoptosis, the release of cytokines and the chemotaxis of macrophages, while the effects were reduced in HRGECs transfected with a miR-650 inhibitor. The existence of a conserved miR-650 binding site on the 3'-untranslated region of BCL11B mRNA was predicted by computational algorithms and confirmed by a luciferase reporter assay. Knockdown of BCL11B with small interfering RNA (siRNA) significantly increased the apoptotic rate and significantly decreased the proliferation ability of HRGECs compared with the negative control group. HRGECs transfected with a combination of BCL11B siRNA and the miR-650 mimic demonstrated a significant increase in the rate of apoptosis compared with the control. These results suggest that the upregulation of miR-650 contributes to the development of acute renal allograft rejection by suppression of BCL11B, which leads to apoptosis and inflammatory responses. Thus, miR-650 and BCL11B may represent potential therapeutic targets for the prevention of acute renal allograft rejection.

PMID: 29039465 [PubMed - as supplied by publisher]

Mutations in INF2 may be associated with renal histology other than focal segmental glomerulosclerosis.

Thu, 10/19/2017 - 12:45
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Mutations in INF2 may be associated with renal histology other than focal segmental glomerulosclerosis.

Pediatr Nephrol. 2017 Oct 06;:

Authors: Büscher AK, Celebi N, Hoyer PF, Klein HG, Weber S, Hoefele J

Abstract
BACKGROUND: In 2010, INF2 mutations were associated with autosomal-dominant focal segmental glomerulosclerosis (FSGS), clinically presenting with moderate proteinuria in adolescence. However, in the meantime, cases with more severe clinical courses have been described, including progression to end-stage renal disease (ESRD) during childhood. INF2 mutations in patients with isolated FSGS are clustered in exons 2 to 4, encoding the diaphanous inhibitory domain, involved in the regulation of the podocyte actin cytoskeleton.
METHODS: We report a family with 14 affected individuals (autosomal-dominant mode of inheritance), most of whom presented with nephrotic-range proteinuria, hypertension, and progressive renal failure. Four members received a kidney transplant without disease recurrence. Two patients underwent renal biopsy with the result of minimal-change glomerulopathy and IgA nephropathy respectively. We performed mutational analysis of ACTN4, CD2AP, COQ6, INF2, LAMB2, NPHS1, NPHS2, PLCE1, TRPC6, and WT1 in the index patient by next-generation sequencing. Additionally, in 6 affected and 2 unaffected family members target diagnostics were performed.
RESULTS: We identified a novel heterozygous mutation c.490G>C (p.(Ala164Pro) in exon 3 of the INF2 gene in the index patient and 6 additionally examined affected family members. In silico analysis predicted it as "probably damaging". Additionally, three patients and 2 unaffected relatives harbored a novel heterozygous variant in ACTN4 (c.1149C>G, p.(Ile383Met)) with uncertain pathogenicity.
CONCLUSION: Mutations in INF2 are associated with familial proteinuric diseases - irrespective of the presence of FSGS and in the case of rapid disease progression. Therefore, mutational analysis should be considered in patients with renal histology other than FSGS and severe renal phenotype.

PMID: 29038887 [PubMed - as supplied by publisher]

Expression and Clinical Significance of Tissue Inhibitor of Metalloproteinases-1 (TIMP-1) and a Disintegrin and Metalloproteinase with Thrombospondin Type 1 Motif 1 (ADAMTS1) in Post-Kidney-Transplant Bladder Tumors.

Thu, 10/19/2017 - 12:45
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Expression and Clinical Significance of Tissue Inhibitor of Metalloproteinases-1 (TIMP-1) and a Disintegrin and Metalloproteinase with Thrombospondin Type 1 Motif 1 (ADAMTS1) in Post-Kidney-Transplant Bladder Tumors.

Ann Transplant. 2017 Oct 17;22:622-630

Authors: Xue W, Zhang Z, Zeng S, Xu Y, Zhang Q, Wang W, Zhang Y, Zhang X, Hu X

Abstract
BACKGROUND To investigate the expression and clinical significance of tissue inhibitor of metalloproteinases-1 (TIMP-1) and a disintegrin and metalloproteinase with thrombospondin type 1 motif 1 (ADAMTS1) in post-kidney-transplant bladder tumors. MATERIAL AND METHODS A total of 27 patients with new bladder tumors occurring after surgical kidney transplants (the experimental group) and 56 patients with conventional new bladder tumors (the control group) were included in this study. All the patients were confirmed to have transitional cell carcinomas by postoperative pathological examination. Fifteen pairs of new bladder tumor specimens (from each of the 2 groups) were selected and subjected to whole-genome oligonucleotide microarray screening to determine the differences in gene expression profiles and analysis using the biomolecule annotation system. Subsequently, quantitative real-time polymerase chain reaction (qRT-PCR), immunohistochemistry, and Western blot analysis were performed to determine and compare differences in the expression of TIMP-l and ADAMTS1 in the urothelial tumors of the 2 groups. RESULTS Analysis of co-differentially expressed genes showed 23 groups of pathways with significant differences (P<0.05) and included immunosuppression and tumor development and progression. TIMP-l expression was significantly higher in the experimental group than in the control group, whereas ADAMTS1 expression was significantly lower in the experimental group than in the control group (P<0.05). CONCLUSIONS Significant differences in gene expression profiles were observed between patients with post-kidney transplant bladder tumors and those with conventional bladder tumors, and the expression of TIMP-1 and ADAMTS1 has important significance for the diagnosis of post-kidney-transplant bladder tumors.

PMID: 29038419 [PubMed - in process]

Factors Associated With Lumbar and Femoral Bone Mineral Density in Kidney Transplants Candidates.

Thu, 10/19/2017 - 12:45
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Factors Associated With Lumbar and Femoral Bone Mineral Density in Kidney Transplants Candidates.

Iran J Kidney Dis. 2017 Oct;11(5):379-384

Authors: Aghighi M, Mahdavi Mazdeh M, Nafar M, Rakhshan V

Abstract
INTRODUCTION: Data on risk factors associated with low bone mineral density are limited in patients with end-stage renal disease. This study evaluated the factors deemed associated with lumbar and femoral Z and T scores.
MATERIALS AND METHODS: Clinical and demographic data of 98 patients waiting for kidney transplantation were collected, as well as lumbar and femoral bone densitometries, before transplantation. Osteoporosis and osteopenia and factors associated with bone mineral density were assessed.
RESULTS: According to the femoral T score, 38.8% (95% confidence interval [CI], 29.1% to 48.4%), 44.9% (95% CI, 35.1% to 54.7%), and 16.3% (95% CI, 9.0% to 23.6%) of the patients had normal bone density, osteopenia, and osteoporosis, respectively. According to the lumbar T score, 54.1% (95% CI, 44.2% to 63.9%), 33.7% (95% CI, 24.3% to 44.0%), and 12.2% (95% CI, 5.8% to 18.7%) of the patients had normal density, osteopenia, and osteoporosis, respectively. Age, serum levels of creatinine and parathyroid hormone, and use of calcitriol and calcium carbonate were associated with femoral densitometry scores. Serum total protein level, Rh-negative status, and B blood type were associated with the lumbar scores.
CONCLUSIONS: Parathyroid hormone contributed to bone loss in our kidney transplant candidates, and B and Rh-negative blood types were associated with a higher risk of lumbar osteoporosis while total protein was negatively associated with the risk of bone loss. Calcitriol might improve femoral mineral density, but calcium carbonate was negatively associated with femoral bone density. Age and higher creatinine levels were associated with higher femoral bone densities.

PMID: 29038394 [PubMed - in process]

Effect of Statins on Patients and Graft Survival in Kidney Transplant Recipients: a Survival Meta-analysis.

Thu, 10/19/2017 - 12:45
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Effect of Statins on Patients and Graft Survival in Kidney Transplant Recipients: a Survival Meta-analysis.

Iran J Kidney Dis. 2017 Oct;11(5):329-338

Authors: Rostami Z, Moteshaker Arani M, Salesi M, Safiabadi M, Einollahi B

Abstract
INTRODUCTION: Modifying cardiovascular risk factors is very important for the patients after kidney transplantation. Statins are a potentially beneficial intervention for kidney transplant patients, and the effect of statins on cardiovascular outcomes in patients with chronic kidney disease varies according to the stages. This systematic review summarizes the potential beneficial effects of statins on kidney allograft outcome.
MATERIALS AND METHODS: A systematic review and meta-analysis was conducted by literature search using the PubMed, Science Direct, Scopus, ISI Web of Knowledge, and Google Scholar. Articles published after 2000 reporting hazard ratios (HRs) for the effect of statins on patient and graft survival of kidney transplant patients were included.
RESULTS: Seven articles were included in the systematic review, involving 1870 kidney transplant patients that received statins and 3339 kidney transplant patients as the control group. Statins has no protective effect on transplant rejection, graft survival or patient survival after kidney transplantation. The effect of statins on graft survival, however, was significant when adjusted for factors such as age, sex, and serum creatinine level (HR, 0.80; 95% CI, 0.69 to 0.92; P = .003). Similarly, patient survival was significantly better with statin use (adjusted HR, 0.75; 95% CI, 0.63 to 0.88; P = .003).
CONCLUSIONS: The present study may provide valuable information on the potential beneficial effects of statins in kidney allograft recipients. Meta-analysis showed that the use of statins correlated independently with improved patient and graft survival after kidney transplantation.

PMID: 29038386 [PubMed - in process]

Nephrosphere-Derived Cells are Induced to Multilineage Differentiation when Cultured on Human Decellularized Kidney Scaffolds.

Thu, 10/19/2017 - 12:45
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Nephrosphere-Derived Cells are Induced to Multilineage Differentiation when Cultured on Human Decellularized Kidney Scaffolds.

Am J Pathol. 2017 Oct 13;:

Authors: Bombelli S, Meregalli C, Scalia C, Bovo G, Torsello B, De Marco S, Cadamuro M, Viganò P, Strada G, Cattoretti G, Bianchi C, Perego RA

Abstract
In end-stage chronic kidney disease, the option of organ transplantation is limited due to the scarce availability of kidneys. The combination of stem cell research, regenerative medicine, and tissue engineering seems a promising approach to produce new transplantable kidneys. Currently, the possibility to repopulate naturally obtained scaffolds with cells of different sources is advancing. Our aim was to test, for the first time, whether the nephrosphere (NS) cells, composed by renal stem/progenitor-like cells, were able to repopulate different nephron portions of renal extracellular matrix scaffolds obtained after decellularization of human renal tissue slices. Our decellularization protocol enabled us to obtain a completely acellular renal scaffold while maintaining the extracellular matrix structure and composition in terms of collagen IV, laminin, and fibronectin. NS cells, cultured on decellularized renal scaffolds with basal medium, differentiated into proximal and distal tubules as well as endothelium, as highlighted by histology and by the specific expression of epithelial CK 8.18, proximal tubular CD10, distal tubular CK7, and endothelial vWf markers. Endothelial medium promoted the differentiation toward the endothelium, whereas epithelial medium toward epithelium. NS cells seem to be a good tool for scaffold repopulation, paving the way for experimental investigations focused on whole-kidney reconstruction.

PMID: 29037855 [PubMed - as supplied by publisher]

Establishment of calculated panel reactive antibody and its potential benefits in improving the kidney allocation strategy in Taiwan.

Thu, 10/19/2017 - 12:45
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Establishment of calculated panel reactive antibody and its potential benefits in improving the kidney allocation strategy in Taiwan.

J Formos Med Assoc. 2017 Oct 13;:

Authors: Shen SW, Chang CK, Gao YS, Hsu PJ, Cheng SC, Liu FY, Lo SC

Abstract
BACKGROUND/PURPOSE: Renal transplant candidates who are highly sensitized to human leukocyte antigens (HLAs) tend to wait longer to find a matched donor and have poor outcomes. Most organ-sharing programs prioritize highly sensitized patients in the allocation scoring system. The HLA sensitization status is traditionally evaluated by the panel-reactive antibody (PRA) assay. However, this assay is method dependent and does not consider the ethnic differences in HLA frequencies. A calculated PRA (cPRA), based on a population's HLA frequency and patients' unacceptable antigens (UAs), correctly estimates the percentage of donors suitable for candidates. The Taiwan Organ Registry and Sharing Center does not prioritize sensitized patients. We propose that the incorporation of the cPRA and UAs into the renal allocation program will improve the local kidney allocation policy.
METHODS: We established a cPRA calculator using 6146 Taiwanese HLA-A, -B, -C, -DR, and -DQ phenotypes. We performed simulated allocation based on the concept of acceptable mismatch for 76 candidates with cPRA values exceeding 80%.
RESULTS: We analyzed 138 waitlisted renal transplant candidates at our hospital, and we determined that the concordance rate of the cPRA and PRA for highly sensitized (%PRA > 80%) candidates was 92.5%, which decreased to 20% for those with %PRA < 80%. We matched 76 highly sensitized patients based on acceptable mismatch with the HLA phenotypes of 93 cadaver donors. Forty-six patients (61%) found at least one suitable donor.
CONCLUSION: The application of the cPRA and acceptable mismatch can benefit highly sensitized patients and reduce positive lymphocyte cytotoxicity crossmatch.

PMID: 29037453 [PubMed - as supplied by publisher]

The efficacy and stability of an information and communication technology-based centralized monitoring system of adherence to immunosuppressive medication in kidney transplant recipients: study protocol for a randomized controlled trial.

Thu, 10/19/2017 - 12:45
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The efficacy and stability of an information and communication technology-based centralized monitoring system of adherence to immunosuppressive medication in kidney transplant recipients: study protocol for a randomized controlled trial.

Trials. 2017 Oct 16;18(1):480

Authors: Jung HY, Seong SJ, Choi JY, Cho JH, Park SH, Kim CD, Yoon YR, Kim HK, Huh S, Yoon SH, Lee JS, Kim YL

Abstract
BACKGROUND: Immunosuppression non-adherence in kidney transplant recipients (KTRs) not only increases the risk of medical intervention due to acute rejection and graft loss but burdens the socioeconomic system in the form of increased healthcare costs. An aggressive preemptive effort by healthcare professionals, geared to ensure adherence to immunosuppressants in KTRs, is significant and imperative.
METHODS/DESIGN: This study was designed as a prospective, open-label, multicenter, randomized controlled study aimed at evaluating the efficacy and stability of an information and communication technology (ICT)-based centralized monitoring system in boosting medication adherence in KTRs. One hundred fourteen KTRs registered throughout the year 2017 to 2018 are randomized into either the ICT-based centralized home monitoring system or to ambulatory follow-up. The planned follow-up duration is 6 months. The ICT-based centralized home monitoring system described consists of a smart pill box equipped with personal identification system, a home monitoring system, an electronic Case Report Form (eCRF) system, and a comprehensive clinical trial management system (CTMS). It alerts both patients and medical staff with texts and pill box alarms if there is a dosage/dosing time error or a missed dose. Medication adherence and transplant outcomes for the follow-up period are compared between the two groups, while patient satisfaction as well as the stability and cost-effectiveness of the ICT-based monitoring system are to be evaluated.
DISCUSSION: This on-going study is expected to determine if consistent use of the ICT-based centralized monitoring system described could maximize mediation adherence and subsequently enhance transplant outcomes in KTRs. Further, it would lay the foundation for successful implementation of this ICT-based monitoring system for effective management of medication adherence in KTRs.
TRIALS REGISTRATION: ClinicalTrials.gov, Identifier: NCT03136588 . Registered on 20 April 2017.

PMID: 29037222 [PubMed - in process]

Naturalizing activity and safety of human monoclonal antibodies against of hepatitis C virus.

Thu, 10/19/2017 - 12:45
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Naturalizing activity and safety of human monoclonal antibodies against of hepatitis C virus.

Hum Antibodies. 2017 Sep 29;:

Authors: Abelhafez TH, Tabll AA, El-Awady MK, Mashaly MM, El Shenawy R, El-Abd YS, Shaker MH, Abdel Malak CA

Abstract
AIM: Assessment of neutralizing activity of the human monoclonal antibodies against HCV and also study its safety in experimental small animals (Swiss mice).
MATERIALS AND METHODS: Assessment of neutralizing activity of the human monoclonal antibodies against HCV envelope regions (E1, E2) by two methods (by HCV cc infectious system and by using positive HCV positive serum as source of HCV particles (neutralizing assay 2). Dot ELISA were used to study the activity of the generated antibodies. We tested the safety and toxicity of the generated human antibodies by assessment the changes in biochemistry of liver function tests and changes in kidney function test, Complete blood counts (CBC) and study the pathological changes with different concentration of purified human antibodies.
RESULTS: Human Abs # 5 & 11 showed neutralizing activity by (neutralizing assay 2) but were not neutralizing by HCV cc assay. Human Abs # 12 & 15 showed neutralizing activity by two methods i.e our generated human antibodies Abs# 5 &11 & 12 & 15 were neutralizing for HCV genotype 4a and Abs # 12 & 15 were neutralizing for HCV genotypes 4a and 2a. Liver and kidney functions and CBC results indicated that doses of 10 μg, 100 μg were safe. The histopathological results indicated that the dose of 10 μg of purified human monoclonal antibodies per mouse body weight was safe.
CONCLUSION: The generated human monoclonal antibodies can be used to develop a potent immunotherapy that can be administrated for the post-transplantation patients to prevent the recurrence of HCV infection. Also, the monoclonal antibodies can be used to develop a vaccine against HCV.

PMID: 29036810 [PubMed - as supplied by publisher]

A rare case of cutaneous acanthamoebiasis in a renal transplant patient.

Thu, 10/19/2017 - 12:45
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A rare case of cutaneous acanthamoebiasis in a renal transplant patient.

Dermatol Online J. 2017 Mar 15;23(3):

Authors: Winsett F, Dietert J, Tschen J, Swaby M, Bangert CA

Abstract
A 35-year-old woman receiving immunosuppressionfor renal transplantation presented with a onemonthhistory of tender skin nodules on herbilateral upper extremities. A skin biopsy revealedgranulomatous inflammation in the deep dermisand the subcutaneous fat with foci of necrosis.Within the foci of necrosis were large histiocytoidstructures with prominent nuclei. Periodic acid-Schiffstain revealed a round organism with a thick capsule,consistent with amoebal trophozoites. Testing withthe Center for Disease Control revealed the organismto be Acanthamoeba. Despite antimicrobial therapy,the patient continued to develop subcutaneousnodules that extended to the lower extremities andtrunk and ultimately extended to the bone, causingacanthamoebal osteomyelitis. Throughout thehospital course, the patient remained neurologicallyintact without evidence of central nervousinvolvement. A diagnosis of isolated disseminatedcutaneous acanthamoebiasis secondary to iatrogenicimmunosuppression was made. Historically, mostcases of granulomatous amoebic encephalitisand cutaneous acanthamoebiasis have occurredin patients with HIV/AIDS. However, with the useof newer and more effective immunosuppressiveregimens, both are occurring more frequently inthe setting of iatrogenic immunosuppression. Therare and isolated cutaneous nature of this patient'spresentation makes this case unique.

PMID: 28329521 [PubMed - indexed for MEDLINE]

Increased mortality in haemodialysis patients administered high doses of erythropoiesis-stimulating agents: a propensity score-matched analysis.

Tue, 10/17/2017 - 12:45

Increased mortality in haemodialysis patients administered high doses of erythropoiesis-stimulating agents: a propensity score-matched analysis.

Nephrol Dial Transplant. 2017 Sep 28;:

Authors: Pérez-García R, Varas J, Cives A, Martín-Malo A, Aljama P, Ramos R, Pascual J, Stuard S, Canaud B, Merello JI, ORD group

Abstract
Background: Erythropoiesis-stimulating agents (ESAs) are widely used to treat anaemia in patients with chronic kidney disease. The issue of ESA safety has been raised in multiple studies, with correlates derived for elevated cancer incidence and mortality. Whether these associations are related to ESA dose or the typology of the patient remains obscure.
Methods: A multicentre, observational retrospective propensity score-matched study was designed to analyse the effects of weekly ESA dose in 1679 incident haemodialysis (HD) patients. ESA administration was according to standard medical practice. Patients were grouped as quintiles, according to ESA dose, in order to compare mortality and hospitalization data. Using propensity score matching (PSM), we defined two groups of 324 patients receiving weekly threshold ESA doses of either > or ≤8000 IU.
Results: Kaplan-Meier survival curves indicated significant increases in the risk of mortality in patients administered with high doses of ESAs (>8127.4 IU/week). Multivariate Cox models identified a high ESA dose as an independent predictor for all-cause and cardiovascular (CV) mortality. Moreover, logistic regression models identified high ESA doses as an independent predictor for all-cause, CV and infectious hospitalization. PSM analyses confirmed that weekly ESA doses of >8000 IU constitute an independent predictor of all-cause mortality and hospitalization, even though the adjusted cohort displayed the same demographic features, inflammatory profile, clinical HD parameters and haemoglobin levels.
Conclusions: Our data suggest that ESA doses of >8000 IU/week are associated with an increased risk of all-cause mortality and hospitalization in HD patients.

PMID: 29036505 [PubMed - as supplied by publisher]

Impact of achieved blood pressure on renal function decline and first stroke in hypertensive patients with chronic kidney disease.

Tue, 10/17/2017 - 12:45

Impact of achieved blood pressure on renal function decline and first stroke in hypertensive patients with chronic kidney disease.

Nephrol Dial Transplant. 2017 Sep 19;:

Authors: Li Y, Liang M, Jiang C, Wang G, Li J, Zhang Y, Fan F, Sun N, Cui Y, He M, Tang G, Yin D, Cheng X, Wang B, Huo Y, Xu X, Hou FF, Xu X, Qin X

Abstract
Background: The effect of achieved blood pressure (BP) on first stroke and renal function decline among hypertensive patients with mild to moderate chronic kidney disease (CKD) is still uncertain.
Methods: In total, 3230 hypertensive patients with estimated glomerular filtration rate 30-60 mL/min/1.73 m 2 and/or proteinuria were included in the present analyses. Eligible participants were randomly assigned to a daily treatment of a combined enalapril 10 mg and folic acid 0.8 mg tablet or an enalapril 10 mg tablet alone. Participants were followed up every 3 months. The study outcomes included first stroke and the progression of CKD.
Results: The median antihypertensive treatment duration was 4.7 years. Compared with participants with a time-averaged on-treatment systolic blood pressure (SBP) of 135 to ≤140 mmHg, the incidence of total first stroke [1.7% versus 3.3%; hazard ratio (HR), 0.51; 95% confidence interval (CI): 0.26-0.99] and ischemic stroke (1.3% versus 2.8%; HR, 0.46; 95% CI: 0.22-0.98) decreased significantly in those with a time-averaged SBP of ≤135 mmHg. Furthermore, a time-averaged diastolic blood pressure (DBP) of ≤80 mmHg, compared with a time-averaged DBP level of 80 to ≤90 mmHg, was significantly related to a decreased risk of hemorrhagic stroke (0.2% versus 0.9%; HR, 0.18; 95% CI: 0.04-0.80). However, compared with participants with a time-averaged SBP of 135 to ≤140 mmHg, a lower but non-significant trend of CKD progression was found in those with a time-averaged SBP of ≤130 mmHg.
Conclusions: A BP treatment level of ≤135/80 mmHg, compared with a BP treatment level of 135-140/80-90 mmHg, could lead to a decreased risk of first stroke in hypertensive patients with mild-to-moderate CKD.

PMID: 29036427 [PubMed - as supplied by publisher]

Factors associated to acceptable treatment adherence among children with chronic kidney disease in Guatemala.

Tue, 10/17/2017 - 12:45

Factors associated to acceptable treatment adherence among children with chronic kidney disease in Guatemala.

PLoS One. 2017;12(10):e0186644

Authors: Ramay BM, Cerón A, Méndez-Alburez LP, Lou-Meda R

Abstract
Pediatric patients with Chronic Kidney Disease face several barriers to medication adherence that, if addressed, may improve clinical care outcomes. A cross sectional questionnaire was administered in the Foundation for Children with Kidney Disease (FUNDANIER, Guatemala City) from September of 2015 to April of 2016 to identify the predisposing factors, enabling factors and need factors related to medication adherence. Sample size was calculated using simple random sampling with a confidence level of 95%, confidence interval of 0.05 and a proportion of 87%. A total of 103 participants responded to the questionnaire (calculated sample size was 96). Independent variables were defined and described, and the bivariate relationship to dependent variables was determined using Odds Ratio. Multivariate analysis was carried out using logistic regression. The mean adherence of study population was 78% (SD 0.08, max = 96%, min = 55%). The mean adherence in transplant patients was 82% (SD 7.8, max 96%, min 63%), and the mean adherence in dialysis patients was 76% (SD 7.8 max 90%, min 55%). Adherence was positively associated to the mother's educational level and to higher monthly household income. Together predisposing, enabling and need factors illustrate the complexities surrounding adherence in this pediatric CKD population. Public policy strategies aimed at improving access to comprehensive treatment regimens may facilitate treatment access, alleviating economic strain on caregivers and may improve adherence outcomes.

PMID: 29036228 [PubMed - in process]

Drug-induced kidney injury: A large case series from the Berlin Case-Control Surveillance Study
.

Tue, 10/17/2017 - 12:45

Drug-induced kidney injury: A large case series from the Berlin Case-Control Surveillance Study
.

Clin Nephrol. 2017 Oct 16;:

Authors: Douros A, Bronder E, Klimpel A, Erley C, Garbe E, Kreutz R

Abstract
OBJECTIVES: Drug-induced kidney injury (DIKI) may affect patients regardless of their baseline kidney function. Therefore, this study evaluated DIKI in patients with or without previous chronic kidney disease (CKD).
MATERIALS AND METHODS: Potential DIKI cases were ascertained using the network of the Berlin Case-Control Surveillance Study in all 51 Berlin hospitals from April 2010 until December 2011. Via face-to-face interviews and medical chart reviews, information on all previous drug intake, comorbidities, and demographics was gathered. Included were adult patients with a new diagnosis of acute kidney injury or an acute-on-chronic kidney injury, and with an at least "possible" drug etiology based on the standardized causality assessment of the World Health Organization. Excluded were patients with prerenal or postrenal etiology, bacterial interstitial nephritis, or previous renal transplantation.
RESULTS: Overall, 143 patients with DIKI were included in the study (mean age 68.4 ± 15.6 years). Of those, 77 (54%) had prediagnosed CKD. The most common symptom at onset was anuria/oliguria, while 73 patients (51%) underwent renal replacement therapy, and 11 patients (8%) died. Cardiovascular drugs, such as furosemide, torasemide, hydrochlorothiazide, and ramipril (33%), systemic anti-infectives, such as vancomycin (23%), and musculoskeletal drugs, such as ibuprofen and diclofenac (15%), were most commonly causal for DIKI. Of the 37 patients with DIKI caused by nonsteroidal anti-inflammatory drugs (NSAIDs), 20 (54%) had prediagnosed CKD.
CONCLUSION: Nephrotoxicity can be caused by numerous medications, highlighting the importance of increased vigilance among physicians. Moreover, NSAIDs seem to exhibit nephrotoxic properties even in patients with normal baseline kidney function.
.

PMID: 29035197 [PubMed - as supplied by publisher]

Generation of a KCNJ11 homozygous knockout human embryonic stem cell line WAe001-A-12 using CRISPR/Cas9.

Tue, 10/17/2017 - 12:45

Generation of a KCNJ11 homozygous knockout human embryonic stem cell line WAe001-A-12 using CRISPR/Cas9.

Stem Cell Res. 2017 Oct;24:89-93

Authors: Yuan F, Guo D, Gao G, Liu Y, Xu Y, Wu Y, Yang F, Ke X, Lai K, Hong L, Li YX

Abstract
The ATP-sensitive potassium channel is an octameric complex, and one of its subunits, namely Kir6.2, is encoded by the KCNJ11 gene. Mutations in KCNJ11 result in hyperinsulinism or diabetes mellitus, associated with abnormal insulin secretion. Here, using CRISPR/Cas9 editing, we established a homozygous mutant KCNJ11 cell line, WAe001-A-12, which was generated by a 62-bp deletion in the coding sequence of the human embryonic stem cell line H1. It was confirmed that this deletion in the KCNJ11 gene did not affect the protein expression levels of key pluripotent factors. Additionally, normal karyotype and differentiation potency were observed for the cell line.

PMID: 29034901 [PubMed - in process]

Editorial: Fighting Against Kidney Injury.

Tue, 10/17/2017 - 12:45

Editorial: Fighting Against Kidney Injury.

Curr Protein Pept Sci. 2017;18(12):1182

Authors: Rong R

PMID: 29034830 [PubMed - in process]

The prognostic value of the furosemide stress test in predicting delayed graft function following deceased donor kidney transplantation.

Tue, 10/17/2017 - 12:45

The prognostic value of the furosemide stress test in predicting delayed graft function following deceased donor kidney transplantation.

Biomarkers. 2017 Oct 16;:1-9

Authors: McMahon BA, Koyner JL, Novick T, Menez S, Moran RA, Lonze BE, Desai N, Alasfar S, Borja M, Merritt WT, Ariyo P, Chawla LS, Kraus E

Abstract
OBJECTIVES AND METHODS: The Furosemide Stress Test (FST) is a novel dynamic assessment of tubular function that has been shown in preliminary studies to predict patients who will progress to advanced stage acute kidney injury, including those who receive renal replacement therapy (RRT). The aim of this study is to investigate if the urinary response to a single intraoperative dose of intravenous furosemide predicts delayed graft function (DGF) in patients undergoing deceased donor kidney transplant.
RESULTS: On an adjusted multiple logistic regression, a single 100 mg dose of intraoperative furosemide after the anastomosis of the renal vessels (FST) predicted the need for RRT at 2 and 6 h post kidney transplantation (KT). Recipient urinary output was measured at 2 and 6 h post furosemide administration. In receiver-operating characteristic (ROC) analysis, the FST predicted DGF with an area-under-the curve of 0.85 at an optimal urinary output cut-off of <600 mls at 6 h with a sensitivity of and a specificity of 83% and 74%, respectively.
CONCLUSIONS: The FST is a predictor of DGF post kidney transplant and has the potential to identify patients requiring RRT early after KT.

PMID: 29034718 [PubMed - as supplied by publisher]

Clodronate Improves Survival of Transplanted Hoxb8 Myeloid Progenitors with Constitutively Active GMCSFR in Immunocompetent Mice.

Tue, 10/17/2017 - 12:45
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Clodronate Improves Survival of Transplanted Hoxb8 Myeloid Progenitors with Constitutively Active GMCSFR in Immunocompetent Mice.

Mol Ther Methods Clin Dev. 2017 Dec 15;7:60-73

Authors: Lee S, Kivimäe S, Szoka FC

Abstract
New methods to produce large numbers of myeloid progenitor cells, precursors to macrophages (MΦs), by maintaining Hoxb8 transcription factor activity(1) has reinvigorated interest in MΦ cell therapies. We generated Hoxb8-dependent myeloid progenitors (HDPs) by transducing lineage-negative bone marrow cells with a constitutively expressed Hoxb8 flanked by loxP. HDPs proliferate indefinitely and differentiate into MΦ when Hoxb8 is removed by a tamoxifen-inducible Cre. We genetically modified HDPs with a constitutively active GMCSF receptor and the tamoxifen-induced transcription factor IRF8, which we have termed "HDP-on." The HDP-on proliferates without GMCSF and differentiates into the MΦ upon exposure to tamoxifen and ruxolitinib (GMCSF inhibitor via JAK1/2 blockade). We quantified the biodistribution of HDPs transplanted via intraperitoneal injection into immunodeficient NCG mice with a luciferase reporter; HDPs are detected for 14 days in the peritoneal cavity, liver, spleen, kidney, bone marrow, brain, lung, heart, and blood. In immunocompetent BALB/c mice, HDP-on cells, but not HDPs, are detected 1 day post-transplantation in the peritoneal cavity. Pretreatment of BALB/c mice with liposomal clodronate significantly enhances survival at day 7 for HDPs and HDP-on cells in the peritoneal cavity, spleen, and liver, but cells are undetectable at day 14. Short-term post-transplantation survival of HDPs is significantly improved using HDP-on and liposomal clodronate, opening a path for MΦ-based therapeutics.

PMID: 29034260 [PubMed]

Food strategies of renal atrophy based on Avicenna and conventional medicine.

Tue, 10/17/2017 - 12:45
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Food strategies of renal atrophy based on Avicenna and conventional medicine.

J Tradit Complement Med. 2017 Oct;7(4):375-379

Authors: Mahjour M, Khoushabi A, Miri Ghale Novi M, Feyzabadi Z

Abstract
Kidneys have an important role in the body. Any damage to kidney role can damage many organs of the body. Traditional Persian Medicine (TPM) or Iranian traditional medicine (ITM) is an ancient temperamental medicine with many literatures about kidney diseases and Avicenna (980-1025 AD) describes kidney diseases in details. This is a review study by searching of the most important clinical and pharmaceutical TPM textbooks such as The Canon of Medicine by Avicenna and scientific data banks using keywords such as "Hozal-e-Kolye", renal atrophy, tubular atrophy, kidney, chronic kidney disease, and end stage renal disease. This paper found that "Hozal-e-Kolye" in TPM texts is the same tubular atrophy in conventional medicine due to some similar symptoms between them. Lifestyle modification and use of proposed foodstuffs can be considered as a complementary medicine in addition to conventional treatments to manage these patients. TPM scholars prescribed some foodstuffs such as camel milk, sheep's milk and Ficus carica for this disease as a complementary management. This study aimed to explain HK (the same tubular atrophy considering their similar symptoms) and introduce some foodstuffs. It seems using of foodstuffs affecting tubular atrophy based on TPM literatures can has a role as a supplemental method in company with conventional medicine management.

PMID: 29034182 [PubMed]

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