Lee J.R.,New York Presbyterian Hospital |
Bang H.,University of California at Davis |
Dadhania D.,New York Presbyterian Hospital |
Hartono C.,New York Presbyterian Hospital |
And 6 more authors.
Transplantation | Year: 2013
Background: Urinary tract infection (UTI) is a frequent, serious complication in kidney allograft recipients. Methods: We reviewed the records of 1166 kidney allograft recipients who received their allografts at our institution between January 2005 and December 2010 and determined the incidence of UTI during the first 3 months after transplantation (early UTI). We used Cox proportional hazards models to determine the risk factors for early UTI and whether early UTI was an independent risk factor for subsequent bacteremia or acute cellular rejection (ACR). Results: UTI, defined as 105 or more bacterial colony-forming units/mL urine, developed in 247 (21%) of the 1166 recipients. Independent risk factors for the first episode of UTI were female gender (hazard ratio [HR], 2.9; 95% confidence intervals [CI], 2.2-3.7; P<0.001), prolonged use of Foley catheter (HR, 3.9; 95% CI, 2.8-5.4; P <0.001), ureteral stent (HR, 1.4; 95% CI, 1.1-1.8; P=0.01), age (HR, 1.1; 95% CI, 1.0-1.2; P=0.03), and delayed graft function (HR, 1.4; 95% CI, 1.0-1.9; P=0.06). Trimethoprim/sulfamethoxazole prophylaxis was associated with a reduced risk of UTI (HR, 0.6; 95% CI, 0.3-0.9; P=0.02). UTI was an independent risk factor for subsequent bacteremia (HR, 2.4; 95% CI, 1.2-4.8; P=0.01). Untreated UTI, but not treated UTI, was associated with an increased risk of ACR (HR, 2.8; 95% CI, 1.3-6.2; P=0.01). Conclusions: Female gender, prolonged use of Foley catheter, ureteral stent, age, and delayed graft function are independent risk factors for early UTI. UTI is independently associated with the development of bacteremia, and untreated UTI is associated with subsequent ACR. Copyright © 2013 by Lippincott Williams & Wilkins.
Tan A.Y.,New York Medical College |
Michaeel A.,New York Medical College |
Liu G.,New York Medical College |
Elemento O.,New York Medical College |
And 6 more authors.
Journal of Molecular Diagnostics | Year: 2014
Autosomal dominant polycystic kidney disease (ADPKD) is caused by mutations in PKD1 and PKD2. However, genetic analysis is complicated by six PKD1 pseudogenes, large gene sizes, and allelic heterogeneity. We developed a new clinical assay for PKD gene analysis using paired-end next-generation sequencing (NGS) by multiplexing individually bar-coded long-range PCR libraries and analyzing them in one Illumina MiSeq flow cell. The data analysis pipeline has been optimized and automated with Unix shell scripts to accommodate variant calls. This approach was validated using a cohort of 25 patients with ADPKD previously analyzed by Sanger sequencing. A total of 250 genetic variants were identified by NGS, spanning the entire exonic and adjacent intronic regions of PKD1 and PKD2, including all 16 pathogenic mutations. In addition, we identified three novel mutations in a mutation-negative cohort of 24 patients with ADPKD previously analyzed by Sanger sequencing. This NGS method achieved sensitivity of 99.2% (95% CI, 96.8%-99.9%) and specificity of 99.9% (95% CI, 99.7%-100.0%), with cost and turnaround time reduced by as much as 70%. Prospective NGS analysis of 25 patients with ADPKD demonstrated a detection rate comparable with Sanger standards. In conclusion, the NGS method was superior to Sanger sequencing for detecting PKD gene mutations, achieving high sensitivity and improved gene coverage. These characteristics suggest that NGS would be an appropriate new standard for clinical genetic testing of ADPKD. © 2014 American Society for Investigative Pathology and the Association for Molecular Pathology. Published by Elsevier Inc. All rights reserved.
Tan Y.-C.,New York Medical College |
Michaeel A.,New York Medical College |
Blumenfeld J.,New York Medical College |
Blumenfeld J.,Rogosin Institute |
And 4 more authors.
Journal of Molecular Diagnostics | Year: 2012
Genetic testing of PKD1 and PKD2 is useful for the diagnosis and prognosis of autosomal dominant polycystic kidney disease; however, analysis is complicated by the large transcript size, the complexity of the gene region, and the high level of gene variations. We developed a novel mutation screening assay for PKD1 by directly sequencing long-range (LR) PCR products. By using this method, the entire PKD1 coding region was amplified by nine reactions, generating product sizes from 2 to 6 kb, circumventing the need for specific PCR amplification of individual exons. This method was compared with direct sequencing used by a reference laboratory and the SURVEYOR-WAVE Nucleic Acid High Sensitivity Fragment Analysis System (Transgenomic) screening method for five patients with autosomal dominant polycystic kidney disease. A total of 53 heterozygous genetic changes were identified by LR PCR sequencing, including 41 (of 42) variations detected by SURVEYOR nuclease and all 32 variations reported by the reference laboratory, detecting an additional 12 intronic changes not identified by the other two methods. Compared with the reference laboratory, LR PCR sequencing had a sensitivity of 100%, a specificity of 98.5%, and an accuracy of 98.8%; compared with the SURVEYOR-WAVE method, it had a sensitivity of 97.1%, a specificity of 100%, and an accuracy of 99.4%. In conclusion, LR PCR sequencing was superior to the direct sequencing and screening methods for detecting genetic variations, achieving high sensitivity and improved intronic coverage with a faster turnaround time and lower costs, and providing a reliable tool for complex genetic analyses. Copyright © 2012 American Society for Investigative Pathology and the Association for Molecular Pathology. Published by Elsevier Inc. All rights reserved.
Aull M.J.,New York Presbyterian Weill Cornell Medical Center |
Afaneh C.,New York Presbyterian Weill Cornell Medical Center |
Charlton M.,New York Presbyterian Weill Cornell Medical Center |
Serur D.,Rogosin Institute |
And 5 more authors.
American Journal of Transplantation | Year: 2014
Few prospective, randomized studies have assessed the benefits of laparoendoscopic single site donor nephrectomy (LESS-DN) over laparoscopic donor nephrectomy (LDN). Our center initiated such a trial in January 2011, following subjects randomized to LESS-DN versus LDN from surgery through 5 years postdonation. Subjects complete recovery/satisfaction questionnaires at 2, 6 and 12 months postdonation; transplant recipient outcomes are also recorded. One hundred subjects (49 LESS-DN, 51 LDN) underwent surgery; donor demographics were similar between groups, and included a predominance of female, living-unrelated donors, mean age of 47 years who underwent left donor nephrectomy. Operative parameters (overall time, time to extraction, warm ischemia time, blood loss) were similar between groups. Conversion to hand-assist laparoscopy was required in 3 LESS-DN (6.1%) versus 2 LDN (3.9%; p-=-0.67). Questionnaires revealed that 97.2% of LESS-DN versus 79.5% of LDN (p-=-0.03) were 100% recovered by 2 months after donation. No significant difference was seen in satisfaction scores between the groups. Recipient outcomes were similar between groups. Our randomized trial comparing LESS donor nephrectomy to LDN confirms that LESS-DN offers a safe alternative to conventional LDN in terms of intra- and post-operative complications. LDN and LESS-DN offer similar recovery and satisfaction after donation. In a randomized, prospective, parallel group study of laparoscopic versus laparoendoscopic single site donor nephrectomy in 100 kidney donors, the authors find that laparoendoscopic single site donor nephrectomy offers a safe alternative to conventional laparoscopic donor nephrectomy, with similar recovery and satisfaction after donation. © Copyright 2014 The American Society of Transplantation and the American Society of Transplant Surgeons.
Palace Z.J.,Hebrew Home at Riverdale |
Bologa R.,Rogosin Institute
Annals of Long-Term Care | Year: 2015
Patients with end-stage renal disease in a skilled nursing facility typically receive hemodialysis, a time-intensive procedure that is commonly performed off-site, necessitating travel to and from the facility and time missed from skilled rehabilitation and therapeutic activities. Peritoneal dialysis is an alternative available to patients requiring renal replacement therapy, as it can be performed at the bedside during the night, requires no travel to an off-site dialysis center, and can help to maintain continuity in the patient's on-site routines. As the authors present in this case report, development of a peritoneal dialysis program within the skilled nursing facility can, therefore, be a more convenient measure that may help to maintain or enhance quality of life for patients with end-stage kidney failure.
Hudgins L.C.,Rogosin Institute |
Parker T.S.,Rogosin Institute |
Levine D.M.,Rogosin Institute |
Hellerstein M.K.,University of California at Berkeley
Journal of Clinical Endocrinology and Metabolism | Year: 2011
Context: Increased hepatic de novo lipogenesis (DNL) in response to dietary sugar is implicated in dyslipidemia, fatty liver, and insulin resistance. Objective: The aim of the study was to develop a simple outpatient tolerance test for lipogenic sensitivity to dietary sugar. Design and Setting: In inpatients given repeated doses of fructose, protocol 1 compared the acute increase in DNL determined from the percentage of palmitate ("new palmitate") and the percentage of isotopically labeled palmitate ("%DNL") in very low-density lipoprotein triglyceride (TG). Protocol 2 compared the increase in new palmitate in outpatients given three different sugar beverages in a randomized crossover design. Participants: There were 15 lean and overweight volunteers in protocol 1 and 15 overweight volunteers in protocol 2. Interventions: In protocol 1, subjects received 1.4 g/kg fructose in divided oral doses over 6 h; in protocol 2, subjects received 0.5 g/kg fructose, 0.5 g/kg fructose plus 0.5g/kg glucose, or 1 g/kg fructose plus 1g/kg glucose each as a single oral bolus. Main Outcome Measures: We measured the increase in DNL by two methods. Results: After repeated doses of fructose, new palmitate was significantly correlated with the increase in %DNL (Δ, r = 0.814; P < 0.001) and with fasting insulin levels (area under the curve, r = 0.754; P = 0.001). After a single sugar dose, new palmitate showed a dose effect and was greater after fructose plus glucose. Very low-density lipoprotein TG and total TG significantly increased in both protocols. Conclusions: A single oral bolus of fructose and glucose rapidly increases serum TG and TG palmitate in overweight subjects. A dual sugar challenge test could prove useful to identify individuals at risk for carbohydrate-induced dyslipidemia and other adverse effects of increased DNL. Copyright © 2011 by The Endocrine Society.
Serur D.,Rogosin Institute |
Charlton M.,Rogosin Institute
Progress in Transplantation | Year: 2012
In an effort to expand the deceased donor pool, transplant centers have accepted expanded criteria donors as appropriate for many of the patients in the deceased donor pool. Translating this into the living donor pool is more complex. One must consider not only the quality of the organ procured but the consequences that the nephrectomy might have on the living donors for the rest of their lives. This review examines the available data on higher risk donors and the appropriateness, or lack thereof, of accepting them as kidney donors. © 2012 NATCO, The Organization for Transplant Professionals.
Levine D.M.,Rogosin Institute |
Maine G.T.,Abbott Laboratories |
Armbruster D.A.,Abbott Laboratories |
Mussell C.,LGC Ltd |
And 5 more authors.
Clinical Chemistry | Year: 2011
BACKGROUND: Owing to the lack of an internationally recognized tacrolimus reference material and reference method, current LC-MS and immunoassay test methods used to monitor tacrolimus concentrations in whole blood are not standardized. The aim of this study was to assess the need for tacrolimus assay standardization. METHODS: We sent a blinded 40-member whole-blood tacrolimus proficiency panel (0-30 μg/L) to 22 clinical laboratories in 14 countries to be tested by the following assays: Abbott ARCHITECT (n = 17), LC-MS (n = 9), and Siemens Dade Dimension (n = 5). Selected LC-MS laboratories (n = 4) also received a common calibrator set. We compared test results to a validated LC-MS method. Four samples from the proficiency panel were assigned reference values by using exact-matching isotope-dilution mass spectrometry at LGC. RESULTS: The range of CVs observed with the tacrolimus proficiency panel was as follows: LC-MS 11.4%-18.7%, ARCHITECT 3.9%-9.5%, and Siemens Dade 5.0%-48.1%. The range of historical within-site QC CVs obtained with the use of 3 control concentrations were as follows: LC-MS low 3.8%-10.7%, medium 2.0%-9.3%, high 2.3%-9.0%; ARCHITECT low 2.5%-9.5%, medium 2.5%-8.6%, high 2.9%-18.6%; and Siemens/Dade Dimension low 8.7%-23.0%, medium 7.6%-13.2%, high 4.4%-10.4%. Assay bias observed between the 4 LC-MS sites was not corrected by implementation of a common calibrator set. CONCLUSIONS: Tacrolimus assay standardization will be necessary to compare patient results between clinical laboratories. Improved assay accuracy is required to provide optimized drug dosing and consistent care across transplant centers globally. © 2011 American Association for Clinical Chemistry.
Matignon M.,New York Presbyterian Hospital Weill Cornell Medical Center |
Matignon M.,Institut Universitaire de France |
Muthukumar T.,New York Presbyterian Hospital Weill Cornell Medical Center |
Muthukumar T.,New York Presbyterian Hospital |
And 6 more authors.
Transplantation | Year: 2012
BACKGROUND: Identification of risk factors for renal allograft failure after an episode of acute antibody-mediated rejection (AMR) may help the outcome of this difficult-to-treat complication. METHODS: During December 2003 to February 2011, 833 kidney graft recipients underwent 1120 clinically indicated biopsies at our center. We reviewed the biopsy results and identified 87 biopsy specimens from 87 patients positive for the degradation product of complement component 4 (C4d) and acute AMR. We generated Kaplan-Meier survival curves and performed a multivariable analysis using the Cox proportional hazards regression model to identify risk factors for allograft failure after C4d+ acute AMR. RESULTS: Among the 87 patients, 26 had a diagnosis of acute AMR according to the Banff '09 classification schema, 29 had acute AMR and chronic active AMR, 18 had acute AMR and acute T-cell mediated rejection (TCMR), and 14 had acute AMR, chronic active AMR, and acute TCMR. Kaplan-Meier survival estimates showed that concurrent acute TCMR (P=0.001, Mantel-Cox log-rank test), concurrent chronic active AMR (P=0.03), and time to biopsy (P=0.04) are associated with graft survival. The Cox proportional hazards regression analysis identified that concurrent acute TCMR (hazard ratio, 2.59 [95% confidence interval, 1.21-5.55]; P=0.01) and estimated glomerular filtration rate (hazard ratio, 0.65 [95% confidence interval, 0.48-0.88]; P=0.01) are independent risk factors for allograft loss. Concurrent chronic active AMR or time to biopsy was not associated with graft failure by the multivariable Cox analysis. CONCLUSIONS: Our single-center study has elucidated that concurrent acute TCMR in kidney transplant recipients with C4d+ acute AMR is an independent risk factor for graft failure. Level of allograft function at the time of diagnosis was also an independent predictor of graft loss. Copyright © 2012 by Lippincott Williams & Wilkins.
Maningat P.,Rockefeller University |
Gordon B.R.,Rogosin Institute |
Breslow J.L.,Rockefeller University
Current Atherosclerosis Reports | Year: 2013
Statins are highly effective drugs prescribed to millions of people to lower LDL-cholesterol and decrease cardiovascular risk. The benefits of statin therapy seen in randomized clinical trials will only be replicated in real-life if patients adhere to the prescribed treatment regimen. But, about half of patients discontinue statin therapy within the first year, and adherence decreases with time. Patient, physician and healthcare system-related factors play a role in this problem. Recent studies have focused more on the patients' perspectives on non-adherence. Adverse events are cited as the most common cause of statin discontinuation; thus, the healthcare provider must be willing to ally and dialogue with patients to address concerns and assess the risks and benefits of continued statin therapy. © 2012 Springer Science+Business Media New York.