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This functional joint model paper is motivated by a chronic kidney disease study post kidney transplantation. The available kidney organ is a scarce resource because millions of end-stage renal patients are on the waiting list for kidney transplantation. The life of the transplanted kidney can be extended if the progression of the chronic kidney disease stage can be slowed, and so a major research question is how to extend the transplanted kidney life to maximize the usage of the scarce organ resource. The glomerular filtration rate is the best test to monitor the progression of the kidney function, and it is a continuous longitudinal outcome with repeated measures. The patient’s survival status is characterized by time-to-event outcomes including kidney transplant failure, death with kidney function, and death without kidney function. Few studies have been carried out to simultaneously investigate these multiple clinical outcomes in chronic kidney disease stage patients based on a joint model. Therefore, this paper proposes a new functional joint model from this clinical chronic kidney disease study. The proposed joint models include a longitudinal sub-model with a flexible basis function for subject-level trajectories and a competing-risks sub-model for multiple time-to event outcomes. The different association structures can be accomplished through a time-dependent function of shared random effects from the longitudinal process or the whole longitudinal history in the competing-risks sub-model. The proposed joint model that utilizes basis function and competing-risks sub-model is an extension of the standard linear joint models. The application results from the proposed joint model can supply some useful clinical references for chronic kidney disease study post kidney transplantation.

Background: Oftentimes, obese dialysis patients develop a viable dialysis access but the access is too deep for cannulation and needs a superficialization procedure. Methods: We present our 14-patient cohort in whom we performed liposuction to superficialize viable but deep vascular accesses. Out of 14 patients, 12 had arteriovenous fistulas and 2 arteriovenous grafts. The primary end points were the ability to superficialize a completely unusable access and to remove the hemodialysis catheter (3patients), or to significantly extend the useful length of a deep access in which only a very short segment was used and to continue to use the access post-surgery without the need to place a dialysis catheter (11 patients). Results: The study goal was met in 13 out of 14 patients. In two of three patients, the catheters were removed and their access usable length was 14 and 13 cm, respectively. The accesses could be used immediately after liposuction in all patients in which this applied—11 patients. The usable access length increased from a mean of 5 to 12.7 cm. The access mean depth decreased from 10.8 mm pre-surgery to 7 mm post-surgery and 5.3 mm 4 weeks after surgery. The mean volume of fat removed was 43.8 cc. We had only one surgical complication: bleeding that was readily controlled with manual pressure. All patients were discharged to home the same day. Postoperative pain was mild. Conclusion: Liposuction is effective, safe, and seems to be the least invasive technique of superficialization.

Introduction: Home hemodialysis remains underutilized despite observational data indicating more favorable outcomes with home compared with in‐center hemodialysis. The Tablo Hemodialysis system is designed to be easy to learn and use and to facilitate adoption of home hemodialysis. The objective of the current investigational device exemption (IDE) study was to evaluate the safety and efficacy of Tablo managed in‐center by health care professionals and in‐home by patients and/or caregivers. Methods: A prospective, multicenter, open‐label, crossover trial comparing in‐center and in‐home hemodialysis using Tablo. There were 4 treatment periods during which hemodialysis was prescribed 4 times per week: 1‐week Run‐In, 8‐week In‐Center, 4‐week Transition, and 8‐week In‐Home. The primary efficacy endpoint was weekly standard Kt/Vurea ≥ 2.1. The secondary efficacy endpoint was delivery of ultrafiltration (UF) within 10% of prescribed UF. We collected safety and usability data. Findings: Thirty participants enrolled and 28 completed all trial periods. Adherence to the protocol requirement of 4 treatments per week was 96% in‐center and 99% in‐home. The average prescribed and delivered session lengths were 3.4 hours for both the In‐Center and the In‐Home periods. The primary efficacy endpoint for the intention‐to‐treat cohort was achieved in 199/200 (99.5%) of measurements during the In‐Center period and 168/171 (98.3%) In‐Home. The average weekly standard Kt/Vurea was 2.8 in both periods. The secondary efficacy UF endpoint was achieved in the ITT cohort in 94% in both in‐center and in‐home. Two prespecified adverse events (AEs) occurred during the In‐Center period and 6 in the In‐Home period. None of the AEs were deemed by investigators as related to Tablo. The median resolution time of alarms was 8 seconds in‐center and 5 seconds in‐home. Conclusion: Primary and secondary efficacy and safety endpoints were achieved during both In‐Center and In‐Home trial periods. This study confirms that Tablo is safe and effective for home hemodialysis use.

Background Fifteen percent of US adults have chronic kidney disease (CKD). The effect of CKD on the development of different malignancies is unknown. Understanding the effect of CKD on the risk of development of cancer could have important implications for screening and early detection of cancer in these patients. Methods Adult CKD patients [estimated GFR (eGFR) 2] between January 2001 and December 2020 were identified in this single institution study. Patients were divided into four stages of CKD by eGFR. The incidence of cancer and time to development of the first cancer were identified. Multivariable models were used to compare the overall cancer incidence while considering death as a competing risk event and adjusting for relevant covariates (sex, race, diabetes, hypertension, CAD, smoking or not, BMI, and CKD stages). Separate multivariable models of the incidence of cancers were conducted in each age group. Multivariable Cox models were used to fit the overall death adjusting for relevant covariates. Patients were censored at the conclusion of the study period (December 31, 2020). Statistical analysis was performed with SAS software (version 9.4). Results Of the 13,750 patients with a diagnosis of CKD in this cohort, 2,758 (20.1%) developed a malignancy. The median time to development of cancer following a diagnosis of CKD was 8.5 years. Factors associated with the risk of developing cancer in CKD patients included increasing age, male sex and worsening chronic kidney disease, while diabetes was associated with a lower risk of malignancy. On multivariate analysis, the factors associated with increased mortality in patients who developed cancer included increasing age, diabetes and lower eGFR. Conclusion CKD is an increased risk factor for the development of various malignancies. Age appropriate cancer screening should be aggressively pursued in those with progressive CKD.

A thorough preoperative history is an essential component of any procedure. A good history allows the interventionalist to appropriately plan the procedure and the supplies needed, anticipate potential complications, and, ultimately, perform a successful and safe intervention.

Kidney-alone transplant (KAT) candidates may be disadvantaged by the allocation priority given to multi-organ transplant (MOT) candidates. This study identified potential KAT candidates not receiving a given kidney offer due to its allocation for MOT. Using the Organ Procurement and Transplant Network (OPTN) database, we identified deceased donors from 2002 to 2017 who had one kidney allocated for MOT and the other kidney allocated for KAT or simultaneous pancreas-kidney transplant (SPK) (n = 7,378). Potential transplant recipient data were used to identify the "next-sequential KAT candidate" who would have received a given kidney offer had it not been allocated to a higher prioritized MOT candidate. In this analysis, next-sequential KAT candidates were younger (p < .001), more likely to be racial/ethnic minorities (p < .001), and more highly sensitized than MOT recipients (p < .001). A total of 2,113 (28.6%) next-sequential KAT candidates subsequently either died or were removed from the waiting list without receiving a transplant. In a multivariable model, despite adjacent position on the kidney match-run, mortality risk was significantly higher for next-sequential KAT candidates compared to KAT/SPK recipients (hazard ratio 1.55, 95% confidence interval 1.44, 1.66). These results highlight implications of MOT allocation prioritization, and potential consequences to KAT candidates prioritized below MOT candidates.

New treatments, new understanding, and new approaches to translational research are transforming the outlook for patients with kidney diseases. A number of new initiatives dedicated to advancing the field of nephrology-from value-based care to prize competitions-will further improve outcomes of patients with kidney disease. Because of individual nephrologists and kidney organizations in the United States, such as the American Society of Nephrology, the National Kidney Foundation, and the Renal Physicians Association, and international nephrologists and organizations, such as the International Society of Nephrology and the European Renal Association-European Dialysis and Transplant Association, we are beginning to gain traction to invigorate nephrology to meet the pandemic of global kidney diseases. Recognizing the timeliness of this opportunity, the American Society of Nephrology convened a Division Chief Retreat in Dallas, Texas, in June 2019 to address five key issues: (1) asserting the value of nephrology to the health system; (2) productivity and compensation; (3) financial support of faculty's and divisions' educational efforts; (4) faculty recruitment, retention, diversity, and inclusion; and (5) ensuring that fellowship programs prepare trainees to provide high-value nephrology care and enhance attraction of trainees to nephrology. Herein, we highlight the outcomes of these discussions and recommendations to the American Society of Nephrology.

Introduction Recently published results of the investigational device exemption (IDE) trial using the Tablo hemodialysis system confirmed its safety and efficacy for home dialysis. This manuscript reports additional data from the Tablo IDE study on the training time required to be competent in self‐care, the degree of dependence on health care workers and caregivers after training was complete, and participants' assessment of the ease‐of‐use of Tablo. Methods We collected data on the time required to set up concentrates and the Tablo cartridge prior to treatment initiation. We asked participants to rate system setup, treatment, and takedown on a Likert scale from 1 (very difficult) to 5 (very simple) and if they had required any assistance with any aspect of treatment over the prior 7 days. In a subgroup of 15 participants, we recorded the number of training sessions required to be deemed competent to do self‐care dialysis. Findings Eighteen men and 10 women with a mean age of 52.6 years completed the study. Thirteen had previous self‐care experience using a different dialysis system. Mean set up times for the concentrates and cartridge were 1.1 and 10.0 minutes, respectively. Participants with or without previous self‐care experience had similar set‐up times. The mean ease‐of‐use score was 4.5 or higher on a scale from 1 to 5 during the in‐home phase. Sixty‐five percent required no assistance at home and on average required fewer than four training sessions to be competent in managing their treatments. Results were similar for participants with or without previous self‐care experience. Conclusions Participants in the Tablo IDE trial were able to quickly learn and manage hemodialysis treatments in the home, found Tablo easy to use, and were generally independent in performing hemodialysis.

Introduction We recently completed an Investigational Device Exemption (IDE) study in which 30 patients were enrolled (13 patients previously on home hemodialysis (HHD) and 17 patients new to HHD) and treated with the Tablo Hemodialysis System (Outset Medical, Inc., San Jose, CA) for 8 weeks in‐center and 8 weeks in‐home with an interim 2–4 week transition period for home training. Methods In addition to assessments of urea kinetics, events related to safety, and operational issues (e.g., alarm resolution), we obtained data on several parameters of health‐related quality of life, including time to recovery (TTR), the EQ‐5D‐5L (a well‐validated measure of general health status), and the quality of sleep and related symptoms, to further assess the safety of HHD with Tablo. We compared results obtained during the in‐center and in‐home phases of the trial. Results Twenty‐eight of 30 patients (93%) completed all trial periods. Adherence to the prescribed four treatments per week schedule was 96% in‐center and 99% in‐home. Median TTR was 1.5 hours (10th, 90th percentile range 0.17 to 12, mean TTR 3.68 ± 5.88 hours) during the in‐center and 2 hours (10th, 90th percentile range 0 to 6.0, mean TTR 3.04 ± 5.14 hours) during the at‐home phase (Wilcoxon signed rank p = 0.57). Median index values on the EQ‐5D‐5L were similar during the in‐center (0.832, 10th, 90th percentile range 0.617 to 1, mean 0.817 ± 0.165) and in‐home (0.826, 10th, 90th percentile range 0.603 to 1, mean 0.821 ± 0.163) trial phases (Wilcoxon signed rank p = 0.36). Patients reported feeling alert or well‐rested with little difficulty falling or staying asleep or feeling tired and worn out when using Tablo in either environment. Conclusion When using Tablo in‐home, patients reported similar TTR, general health status, and sleep quality and related symptoms compared to using Tablo in‐center. (294 words).

Background and objectives Medical specialty and subspecialty fellowship programs administer subject-specific in-training examinations to provide feedback about level of medical knowledge to fellows preparing for subsequent board certification. This study evaluated the association between the American Society of Nephrology In-Training Examination and the American Board of Internal Medicine Nephrology Certification Examination in terms of scores and passing status. Design, setting, participants, & measurements The study included 1684 nephrology fellows who completed the American Society of Nephrology In-Training Examination in their second year of fellowship training between 2009 and 2014. Regression analysis examined the association between In-Training Examination and first-time Nephrology Certification Examination scores as well as passing status relative to other standardized assessments. Results This cohort included primarily men (62%) and international medical school graduates (62%), and fellows had an average age of 32 years old at the time of first completing the Nephrology Certification Examination. An overwhelming majority (89%) passed the Nephrology Certification on their first attempt. In-Training Examination scores showed the strongest association with first-time Nephrology Certification Examination scores, accounting for approximately 50% of the total explained variance in the model. Each SD increase in In-Training Examination scores was associated with a difference of 30 U (95% confidence interval, 27 to 33) in certification performance. In-Training Examination scores also were significantly associated with passing status on the Nephrology Certification Examination on the first attempt (odds ratio, 3.46 per SD difference in the In-Training Examination; 95% confidence interval, 2.68 to 4.54). An In-Training Examination threshold of 375, approximately 1 SD below the mean, yielded a positive predictive value of 0.92 and a negative predictive value of 0.50. Conclusions American Society of Nephrology In-Training Examination performance is significantly associated with American Board of Internal Medicine Nephrology Certification Examination score and passing status.

Background Zero balance ultrafiltration (Z-BUF) utilizing injectable 8.4% sodium bicarbonate is utilized to treat hyperkalemia and metabolic acidosis associated with cardiopulmonary bypass (CPB). The nationwide shortage of injectable 8.4% sodium bicarbonate in 2017 created a predicament for the care of cardiac surgery patients. Given the uncertainty of availability of sodium bicarbonate solutions, our center pro-actively sought a solution to the sodium bicarbonate shortage by performing Z-BUF with dialysate (Z-BUF-D) replacement fluid for patients undergoing cardiopulmonary bypass. Methods Single-center, retrospective observational evaluation of the first 46 patients at an academic medical center who underwent Z-BUF using dialysate over a period of 150 days with comparison of these findings to a historical group of 39 patients who underwent Z-BUF with sodium chloride (Z-BUF-S) over the preceding 150 days. The primary outcome was the change in whole blood potassium levels pre- and post-Z-BUF-D. Secondary outcomes included changes in pre- and post-Z-BUF-D serum bicarbonate levels and the amount of serum bicarbonate used in each Z-BUF cohort (Z-BUF-D and Z-BUF-S). Results Z-BUF-D and Z-BUF-S both significantly reduced potassium levels during CPB. However, Z-BUF-D resulted in a significantly decreased need for supplemental 8.4% sodium bicarbonate administration during CPB (52 mEq ± 48 vs. 159 mEq ± 85, P Conclusion Z-BUF with dialysate appears to be analternative to Z-BUF with sodium chloride with marked lower utilization of intravenous sodium bicarbonate.

Systemic capillary leak syndrome (SCLS) is a disorder characterized by increased vascular permeability with intermittent acute episodes of profound capillary leak that may result in hypotension or shock. A rarely described chronic form of SCLS (cSCLS) presents as refractory edema, with pleural and/or pericardial effusions and hypoalbuminemia. These entities are differentiated by massive and periodic episodes of capillary leak, which can result in shock in SCLS, and chronic refractory edema in cSCLS. The etiologies of these disorders are poorly understood, but both acute and chronic forms often present with an associated monoclonal gammopathy. Flares of the SCLS have been reduced by treatment with intravenous immune globulin (IVIG). Only six cases of cSCLS have been reported, and previous treatments have included steroids, terbutaline, and theophylline. Based upon the reported responses of SCLS to IVIG, we present the case of a 54-year-old man with cSCLS where ongoing treatment with IVIG resulted in a marked and sustained improvement in the signs and symptoms of the capillary leak syndrome. .

SUMMARYBackground Chronic kidney disease is a growing health problem on a global scale. The increasing prevalence of chronic kidney disease presents an urgent need to better understand the knowledge, confidence and engagement in self-managing the disease. Objectives This study examined group differences in patient activation and health-related quality of life, knowledge, self-management and confidence with managing chronic disease across all five stages of chronic kidney disease. Design The study employed a descriptive correlational design. Settings Participants were recruited from five primary care, three nephrology clinics and one dialysis centre in two Midwestern cities in the United States. Participants The convenience sample included 85 adults with hypertension, diabetes mellitus and chronic kidney disease, including kidney failure, who spoke English. Measurements Seven measurements were used to collect data via telephone interviews with participants not receiving haemodialysis, and face-to-face interviews with those receiving haemodialysis at the beginning of their treatment session. Results Analyses indicated that half the participants were female (50.58%), the mean age was 63.21 years (SD = 13.11), and participants with chronic kidney disease stage 3 were the most activated. Post hoc differences were significant in patient activation and blood pressure self-management and anxiety across chronic kidney disease stages, excluding stage 5. Conclusion Engaging patients in the self-management of their health care and enhancing patients’ ability to self-manage their blood pressure may work to preserve kidney health. Healthcare providers should collaborate with patients to develop strategies that will maintain patients’ health-related quality of life, like reducing anxiety as kidney disease progress.

There are limited data regarding endovascular treatment of arteriovenous graft (AVG) pseudoaneurysms using stent grafts. We performed a comprehensive literature review on the use of stent grafts in the treatment of AVG pseudoaneurysms. We included 10 studies (121 patients). The mean AVG age was 3.1 years (95% confidence interval [CI]: 2.2-4) and pseudoaneurysm mean diameter was 34 mm (95% CI: 23-46). The majority (71%) of the pseudoaneurysms were located on the arterial limb of the AVG and 77% presented with venous anastomosis stenosis requiring angioplasty. The mean number of stents used to treat one lesion was 1.4 (95% CI: 1.3-1.5). The technical success rate of pseudoaneurysm isolation was 100% in all studies and 100% of patients received hemodialysis using the AVG after pseudoaneurysm treatment without the need for catheter placement. The primary patency rates for 1, 3, and 6 months were 81%, 73%, and 24%. Secondary patency was 80%, 77%, and 74% at 1, 3, and 6 months. Arteriovenous graft thrombosis occurred in 12% of patients. Arteriovenous graft infection developed in 35% of cases. Arteriovenous graft pseudoaneurysm treatment using stent grafts is effective in managing even large pseudoaneurysms and has acceptable primary and secondary patency rates. Graft infection was a relatively frequent complication.

Type 1 primary hyperoxaluria is a genetic disorder caused by deficiency of the liver-specific peroxisomal enzyme alanine-glyoxylate aminotransferase. This enzyme deficiency leads to excess oxalate production and deposition of calcium oxalate salts, resulting in kidney failure and systemic oxalosis. Aside from combined liver/kidney transplantation, no curative treatment exists. Various strategies for optimizing dialysis treatment have been evaluated, but neither conventional hemodialysis nor peritoneal dialysis can keep pace with oxalate production in this patient population. In this report, we describe a patient with end-stage renal disease from type 1 primary hyperoxaluria managed with nocturnal home hemodialysis. Performing hemodialysis 8-10 hours each night with blood flow of 350 mL/min and total dialysate volume of 60 L, she has maintained pre- and postdialysis serum oxalate levels at or below the level of supersaturation. We also review published literature regarding oxalate removal in various modalities of dialysis in patients with type 1 primary hyperoxaluria. In our patient, nocturnal hemodialysis has controlled serum oxalate levels better than conventional hemodialysis therapies. Home nocturnal hemodialysis should be considered an option for management of patients with end-stage renal disease from type 1 hyperoxaluria who are awaiting transplantation.

To address issues of antibiotic dosing during sustained low-efficiency dialysis by using available pharmacokinetic data, intermittent and continuous renal replacement therapy dialysis guidelines, and our experience with sustained low-efficiency dialysis.Published clinical trials, case reports, and reviews of antibiotic dosing in humans during sustained low-efficiency dialysis.A search of electronic databases (MEDLINE, PubMed, and Ovid) was conducted by using key words of extended daily dialysis, sustained low-efficiency dialysis, antibiotics, antimicrobial agents, and pharmacokinetics. MEDLINE identified 32 sustained low-efficiency dialysis articles, and PubMed identified 33 articles. All papers describing antibiotic clearance prospectively in patients were considered for this article.We identified nine original research articles and case reports that determined the impact of sustained low-efficiency dialysis on antibiotic clearance in patients. The blood and dialysate flow rates, duration of dialysis, type of filter, and the pharmacokinetic parameters were extracted from each article. If multiple articles on the same drug were published, they were compared for consistency with the aforementioned dialysis parameters and then compared with forms of continuous renal replacement therapy. Antibiotic clearance by sustained low-efficiency dialysis was determined to be similar or higher than continuous renal replacement therapy therapies. The estimated creatinine clearance during sustained low-efficiency dialysis was approximately 60 mL/min to 100 mL/min depending on the blood and dialysate flow rates and the type of filter used.The potential for significant drug removal during an 8-hr-or-longer sustained low-efficiency dialysis session is evident by the limited number of studies available. Because significant amounts of drug may be removed by sustained low-efficiency dialysis combined with altered pharmacokinetic variables in critically ill patients, the risk for suboptimal drug concentrations and pharmacodynamics must be considered. Appropriate dose and calculation of dosing intervals is essential to provide adequate antibiotic therapy in these patients. It is recommended that institutions who utilize sustained low-efficiency dialysis establish dosing guidelines for all pharmacists and physicians to follow to provide consistent delivery of antibiotics at adequate concentrations.

Although the requirements for T lymphocyte homing to lymph nodes (LNs) are well studied, much less is known about the requirements for T lymphocyte locomotion within LNs. Imaging of murine T lymphocyte migration in explanted LNs using two-photon laser-scanning fluorescence microscopy provides an opportunity to systematically study these requirements. We have developed a closed system for imaging an intact LN with controlled temperature, oxygenation, and perfusion rate. Naive T lymphocyte locomotion in the deep paracortex of the LN required a perfusion rate of >13 μm/s and a partial pressure of O2 (pO2) of >7.4%. Naive T lymphocyte locomotion in the subcapsular region was 38% slower and had higher turning angles and arrest coefficients than naive T lymphocytes in the deep paracortex. T lymphocyte activation decreased the requirement for pO2, but also decreased the speed of locomotion in the deep paracortex. Although CCR7−/− naive T cells displayed a small reduction in locomotion, systemic treatment with pertussis toxin reduced naive T lymphocyte speed by 59%, indicating a contribution of Gαi-mediated signaling, but involvement of other G protein-coupled receptors besides CCR7. Receptor knockouts or pharmacological inhibition in the adenosine, PG/lipoxygenase, lysophosphatidylcholine, and sphingosine-1-phosphate pathways did not individually alter naive T cell migration. These data implicate pO2, tissue architecture, and G-protein coupled receptor signaling in regulation of naive T lymphocyte migration in explanted LNs.

Postinfectious glomerulonephritis (PIGN) is a rare etiology of de novo glomerulonephritis following kidney transplantation. To date, there have only been eight cases reported in the literature. We report an additional three patients transplanted at our institution between January 2000 and October 2004 who had clinical and pathologic findings consistent with posttransplant PIGN. All three patients were type 1 diabetics. One had received a cadaveric kidney transplant, one a simultaneous kidney-pancreas transplant, and the third a living related kidney transplant followed by a pancreas transplant. All patients were on triple immunosuppressive therapy with tacrolimus, mycophenolate mofetil, and prednisone. In each case, an acute decline in allograft function developed in association with a known or suspected infectious process, and renal biopsies revealed an immune complex glomerulonephritis with features of PIGN. All regained renal function with treatment of their known or suspected infections and without specific therapies for their glomerulonephritis, including corticosteroids.

We report 2 cases of familial juvenile hyperuricemic nephropathy, a rare autosomal dominant disorder characterized by uromodulin gene mutations leading to hyperuricemia secondary to profound renal uric acid underexcretion, gout, and chronic renal disease. Case 1 involves a 56-year-old woman who underwent a kidney transplant after steady decline in kidney function since the age of 19 years. Her gout had been successfully controlled with varying doses of daily allopurinol. Case 2, the son of case 1, presented with already progressive and debilitating arthritis at the age of 34 years with relatively stable chronic renal failure that was also subsequently managed with daily allopurinol and judicious anti-inflammatory prophylaxis.

The present study evaluated interleukin-6 (IL6) as a predictor of mortality in patients and sepsis with acute kidney injury (AKI) receiving sustained low-efficiency dialysis (SLED) and antibiotic therapy.Seven patients with sepsis receiving antibiotics and SLED for AKI were studied. Blood was obtained at baseline prior to SLED and antibiotics, during SLED, and then after stopping SLED. IL6 concentrations were measured using an enzyme-linked immunosorbent assay (ELISA).Mean plasma IL6 concentrations ranged between 700 and 900 pg/ml for the first 8 h after starting SLED but was significantly lower after discontinuation of SLED (200-250 pg/ml) (p=0.0044). Three out of seven patients survived to be discharged from the hospital and all three had significantly lower concentrations of IL6 during the first 8 h compared to those who died in the hospital (p0.0001).The combination of SLED and antibiotic therapy was unable to lower the initial high plasma IL6 concentrations, and high initial IL6 concentrations predicted in-hospital mortality.

Lipopolysaccharide (LPS) causes apoptotic deletion of CD4+CD8+thymocytes, a phenomenon that has been linked to immune dysfunction and poor survival during sepsis. Given the abundance of thromboxane-prostanoid (TP) receptors in CD4+CD8+thymocytes and in vitro evidence that thromboxane A2(TXA2) causes apoptosis of these cells, we tested whether enhanced generation of TXA2plays a role in LPS-induced thymocyte apoptosis. Mice injected with 50 μg of LPS intraperitoneally displayed a marked increase in generation of TXA2and prostaglandin E2in the thymus as well as apoptotic deletion of CD4+CD8+thymocytes. Administration of indomethacin or rofecoxib inhibited prostanoid synthesis but did not affect thymocyte death. In contrast, thymocyte apoptosis in response to LPS was significantly attenuated in TP-deficient mice. These studies indicate that TXA2mediates a portion of apoptotic thymocyte death caused by LPS. The absence of an effect of global inhibition of prostanoid synthesis suggests a complex role for prostanoids in this model.

Recurrent episodes of acute rejection (AR) and/or the intense immunosuppression used for their treatment have been proposed as risk factors for BK nephritis (BKN; BK refers to the initials of the first patient from whom this polyomavirus was isolated). To further examine the relationship between AR and BKN, we analyzed all kidney transplants performed at our center between January 1999 and August 2001 (n = 286). After a mean follow-up of 737 +/- 22 d, we identified nine cases of BKN (3.1%). The mean time to diagnosis of BKN was 326 +/- 56 d. No patient with BKN had a prior history of AR. During the same period, 62 patients were diagnosed with AR (22%). The mean time to diagnosis of AR was 197 +/- 40 d (p = 0.01 vs. time to diagnosis of BKN). Despite aggressive therapy with methylprednisolone and, in some cases, anti-lymphocyte antibody, none of these patients with AR developed BKN. We compared the baseline characteristics of patients in both groups and found that BKN patients were more likely to be white people (78 vs. 44%, p = 0.05) and male (89 vs. 53%, p = 0.04). Moreover, the mean tacrolimus (TAC) levels before diagnosis were higher in BKN than in AR patients (11.7 +/- 0.5 vs. 6.5 +/- 0.6 ng/mL, p < 0.001). In summary, our study shows that BKN often occurs in the absence of prior episodes of AR. In addition, our findings suggest that white males exposed to higher TAC levels are at greater risk of developing BKN.

Antigens, provided by the allograft, trigger the activation and proliferation of allospecific T cells. As a consequence of this response, effector elements are generated that mediate graft injury and are responsible for the clinical manifestations of allograft rejection. Donor-specific CD8+ cytotoxic T lymphocytes play a major role in this process. Likewise, CD4+ T cells mediate delayed-type hypersensitivity responses via the production of soluble mediators that function to further activate and guide immune cells to the site of injury. In addition, these mediators may directly alter graft function by modulating vascular tone and permeability or by promoting platelet aggregation. Allospecific CD4+ T cells also promote B-cell maturation and differentiation into antibody-secreting plasma cells via CD40-CD40 ligand interactions. Alloantibodies that are produced by these B cells exert most of their detrimental effects on the graft by activating the complement cascade. Alternatively, antibodies can bind Fc receptors on natural killer cells or macrophages and cause target cell lysis via antibody-dependent cell-mediated cytotoxicity. In this review, we discuss these major effector pathways, focusing on their role in the pathogenesis of allograft rejection.

There are limited data regarding endovascular treatment of arteriovenous graft (AVG) pseudoaneurysms using stent grafts. We performed a comprehensive literature review on the use of stent grafts in the treatment of AVG pseudoaneurysms. We included 10 studies (121 patients). The mean AVG age was 3.1 years (95% confidence interval [CI]: 2.2-4) and pseudoaneurysm mean diameter was 34 mm (95% CI: 23-46). The majority (71%) of the pseudoaneurysms were located on the arterial limb of the AVG and 77% presented with venous anastomosis stenosis requiring angioplasty. The mean number of stents used to treat one lesion was 1.4 (95% CI: 1.3-1.5). The technical success rate of pseudoaneurysm isolation was 100% in all studies and 100% of patients received hemodialysis using the AVG after pseudoaneurysm treatment without the need for catheter placement. The primary patency rates for 1, 3, and 6 months were 81%, 73%, and 24%. Secondary patency was 80%, 77%, and 74% at 1, 3, and 6 months. Arteriovenous graft thrombosis occurred in 12% of patients. Arteriovenous graft infection developed in 35% of cases. Arteriovenous graft pseudoaneurysm treatment using stent grafts is effective in managing even large pseudoaneurysms and has acceptable primary and secondary patency rates. Graft infection was a relatively frequent complication.

The pseudoaneurysm is caused by a tear through all the layers of a vessel, allowing a blood collection to form outside the blood vessel, but remaining in continuity with the vessel lumen. The blood is contained by the surrounding tissues and flows in and out of the pseudoaneurysm’s cavity during systole and diastole. The pseudoaneurysm has two components: a cavity and a neck by which the cavity communicates with the lumen of the feeding vessel.

We present a case of arteriovenous graft pseudoaneurysms treated endovascularly with stent grafts and make suggestions regarding the technique of evaluating the pseudoaneurysms and choosing the proper location to deploy the stent grafts to maximize the outcomes and minimize the length of the graft covered by the stent. We also comment on the selection of lesions that are suitable to be treated with this technique.

Steal syndrome is a well-described complication of arteriovenous fistulas used for hemodialysis access. Although distal revascularization with interval ligation appears to offer the greatest likelihood of symptom relief and vascular access salvage, not all fistulas are amenable to this procedure, particularly distal radiocephalic arteriovenous fistulas. In this report, we describe the treatment of steal syndrome in a patient with a distal radiocephalic arteriovenous fistula using a percutaneous approach and endovascular coils. After coil embolization of the distal radial artery and multiple collateral vessels, steal was no longer visualized using angiography, and the patient’s symptoms resolved.

In this study we show that recombinant adenovirus can augment hypoxanthine-guanine phosphoribosyltransferase (HPRT) levels in the central nervous system (CNS) of HPRT-deficient mice. Recombinant adenovirus containing the cDNA for rat HPRT (rHPRT) expressed from the Rous sarcoma virus LTR (RSV LTR) was constructed (AdRSVrHPRT). AdRSVrHPRT was injected into the right caudate nucleus of 7-week-old HPRT-deficient mice. Brains were analyzed for gene transfer, transgene expression and function by DNA PCR, in situ RNA hybridization, and enzyme bioactivity. The results show that rHPRT cDNA delivered by an adenoviral vector can augment HPRT levels in brain tissue and documents the utility of gene transfer to restore HPRT activity in an HPRT-deficient CNS.

We present a 58-year-old man with recurrent multiple myeloma treated with 2 autologous stem cell transplantations. He was admitted for dyspnea and found to have severe type B lactic acidosis with serum lactate level of 193.6 mg/dL. This case reviews malignancy-associated type B lactic acidosis and discusses its etiology, pathogenesis, and management.

A 35-year-old man presents with a 1-week history of progressive shortness of breath and an episode of hemoptysis earlier today. For the past 2 days he has had decreased urine volume and dark colored urine. He has no past medical history and takes no medications. Blood pressure is 145/85 mmHg. Pulse is 110 beats per minute. Temperature is 36.8 °C. Pulse oximetry is 87 % on room air. He is anxious and slightly pale. Pulmonary exam reveals bibasilar crackles. The remainder of his exam is unremarkable. His laboratory data is notable for a hemoglobin level of 10.9 g/dL and serum creatinine of 2.7 mg/dL. His chest X-ray shows bilateral pulmonary infiltrates.

The American Society of Nephrology and the fellowship training program directors in conjunction with the National Board of Medical Examiners developed a comprehensive assessment of medical knowledge for nephrology fellows in-training. This in-training examination (ITE) consisted of 150 multiple-choice items covering 11 broad content areas in a blueprint similar to the American Board of Internal Medicine certifying examination for nephrology. Questions consisted of case vignettes to simulate real-life clinical experience. The first examination was given in April 2009 to 682 fellows and six training program directors. Examinees felt that the examination was well structured and relevant to their training experience Longitudinal performance on the examination will be helpful in allowing training programs to utilize results from content areas in identifying deficits in medical knowledge as well as assessing the results of any curriculum changes.

Background. Concurrent chemoradiotherapy with cisplatin is the standard therapy for patients with unresectable locally advanced head and neck squamous cell carcinoma. However, cisplatin administration in patients on hemodialysis is complicated by the need to perform hemodialysis immediately after the infusion. Concurrent chemoradiation with cetuximab has been approved in definitive treatment of locally advanced head and neck cancer. Although cetuximab is not excreted via the kidneys, its use in patients on hemodialysis has not been reported. Methods and Results. We present the case of a 65-year-old man undergoing hemodialysis, with stage IVA squamous cell carcinoma of the hypopharynx. Given the logistics of performing hemodialysis immediately postcisplatin, he received concurrent chemoradiotherapy with cetuximab. He tolerated treatment well with minor side effects. Conclusion. Cetuximab can be safely used in patients with renal impairment. This is the first reported case of the use of cetuximab in a patient undergoing hemodialysis. © 2009 Wiley Periodicals, Inc. Head Neck, 2009

A variety of factors have been proposed to explain arteriovenous fistula primary failures in patients undergoing hemodialysis, including obesity, diabetes mellitus, female sex, and the absence of preoperative vein mapping. In this report, we describe 2 women for whom premature upper-extremity arteriovenous fistula failures occurred in the setting of venographic evidence of soft-tissue compression of the venous outflow with the patient's arm in the adducted position. In each instance, preoperative noninvasive duplex vein mapping showed veins of adequate diameter (0.28 to 0.54 cm), and further evaluation showed no evidence of a hypercoagulable state. Upper-extremity venography was used to assess central venous patency and fully assess the venous vasculature. Unlike the widely patent venous systems seen in the abducted position, venography performed with the upper extremities in adduction showed marked narrowing of the brachial and/or axillary veins. The hemodynamic effects of this narrowing were readily apparent in patient 2 with the appearance of collateral filling of the cephalic vein in the adducted position. Patient 1 had a body mass index of 39 kg/m 2 , and patient 2 had a body mass index of 34 kg/m 2 . Each patient had excess axillary soft tissue that appeared to compress the venous outflow in adduction. To our knowledge, this is the first report to radiographically document soft-tissue compression of the venous outflow of the upper extremity in the adducted position, suggesting a mechanism whereby obesity, or at least excess axillary fat, can lead to premature hemodialysis vascular access failures.

Recurrent episodes of acute rejection (AR) and/or the intense immunosuppression used for their treatment have been proposed as risk factors for BK nephritis (BKN; BK refers to the initials of the first patient from whom this polyomavirus was isolated). To further examine the relationship between AR and BKN, we analyzed all kidney transplants performed at our center between January 1999 and August 2001 (n = 286). After a mean follow-up of 737 +/- 22 d, we identified nine cases of BKN (3.1%). The mean time to diagnosis of BKN was 326 +/- 56 d. No patient with BKN had a prior history of AR. During the same period, 62 patients were diagnosed with AR (22%). The mean time to diagnosis of AR was 197 +/- 40 d (p = 0.01 vs. time to diagnosis of BKN). Despite aggressive therapy with methylprednisolone and, in some cases, anti-lymphocyte antibody, none of these patients with AR developed BKN. We compared the baseline characteristics of patients in both groups and found that BKN patients were more likely to be white people (78 vs. 44%, p = 0.05) and male (89 vs. 53%, p = 0.04). Moreover, the mean tacrolimus (TAC) levels before diagnosis were higher in BKN than in AR patients (11.7 +/- 0.5 vs. 6.5 +/- 0.6 ng/mL, p0.001). In summary, our study shows that BKN often occurs in the absence of prior episodes of AR. In addition, our findings suggest that white males exposed to higher TAC levels are at greater risk of developing BKN.

Eicosanoids are a family of lipid mediators derived from the metabolism of arachidonic acid. Eicosanoids, such as prostanoids and leukotrienes, have a wide range of biological actions including potent effects on inflammation and immunity. It has been almost 20 years since the first reports emerged suggesting a role for eicosanoids in transplantation. Since then, a number of functions have been ascribed to these mediators, ranging from immunomodulation to regulation of allograft hemodynamics. In this review, we will highlight the effects of eicosanoids in transplantation, focusing particularly on evidence provided by gene targeting studies. In the future, pharmacological manipulation of eicosanoids and their receptors may provide a novel approach for controlling inflammation and promoting allograft acceptance.

Marius C Florescu,1 KM Monirul Islam,2 Troy J Plumb,1 Sara Smith-Shull,3 Jennifer Nieman,3 Prasanti Mandalapu11Nephrology Department, 2Institute of Public Health, 3Department of Pharmacy, The Nebraska Medical Center, Omaha, NE, USABackground: Data on the risk factors and clinical course of hungry bone syndrome are lacking in dialysis and renal transplant patients who undergo parathyroidectomy. In this study, we aimed to assess the risks and clinical course of hungry bone syndrome and calcium repletion after parathyroidectomy in dialysis and renal transplant patients.Methods: We performed a retrospective review of parathyroidectomies performed at The Nebraska Medical Center.Results: We identified 41 patients, ie, 30 (73%) dialysis and eleven (27%) renal transplant patients. Dialysis patients had a significantly higher pre-surgery intact parathyroid hormone (iPTH, P

B K polyomavirus nephritis (BKN) has been linked to the newer immunosuppressants tacrolimus (TAC) and mycophenolate mofetil (MMF) even though risk factors for the disease have not been well defined. A recent study, however, suggested that BKN occurs as a complication of the treatment of acute rejection with methylprednisolone. To further examine the relationship between the treatment of acute rejection and BKN, we analyzed all kidney transplants performed at our center between January 1999 and August 2001 (n 286). After a mean follow-up of 622 63 days, we identified 9 cases of BKN (3.1%) using urine electron microscopy. Of these, 8 patients also underwent allograft biopsy, which confirmed the diagnosis. The mean time to diagnosis of BKN was 326 56 days. No patient with BKN had a history of acute rejection. During the same period, 59 (21%) patients were diagnosed with acute rejection and treated with methylprednisolone. The mean time to diagnosis of acute rejection was 197 40 days (P .01, vs time to diagnosis of BKN). None of these patients had subsequent development of BKN during the follow-up period. We compared the characteristics of patients with development of BKN with those of patients who had acute rejection and found that patients with BKN were more likely to be male (89% vs 53%, P .04) and white (78% vs 44%, P .05). Moreover, the mean TAC levels from the time of transplant to the time of diagnosis were higher in the BKN group than in the acute rejection group (12 1 vs 7 1 ng/mL, P .001). The treatment of BKN consisted mainly of a reduction in immunosuppression. MMF was discontinued in 7 of 9 patients, all of whom experienced disappearance of viruria (median time to negative result of urine electron microscopy, 147 days; range, 29-257) and remained independent of dialysis at last follow-up. In 2 of 9 BKN patients, MMF doses were only reduced. Neither patient had clearance of the viruria, and 1 ultimately lost the graft because of the viral infection. Conclusion: Our study does not show an association between acute rejection or its treatment and the development of BKN. Our findings suggest that these conditions tend to affect distinct groups of renal allograft recipients. Although there may be a potential relationship between high TAC levels and BKN, discontinuation of MMF was associated with clearance of viruria and preservation of renal function. From the Departments of Medicine, Nephrology, and Pathology, Duke University Medical Center, Durham, NC. © 2003 Elsevier Inc. All rights reserved. 0955-470X/03/1704-0000$30.00/0 doi:10.1016/j.trre.2003.10.019

Little information is available regarding ciprofloxacin pharmacokinetics and pharmacodynamics in sepsis patients receiving sustained low-efficiency dialysis (SLED). This study determined the pharmacokinetics and simulated pharmacodynamics of ciprofloxacin in ICU patients during SLED.