Immunogenicity of Class I HLA but not preformed low MFI donor specific antibodies correlates with outcomes after first renal transplantation.

BACKGROUND: The role of low levels of circulating donor specific antibodies (DSA) producing negative flow cytometry cross match is not completely defined. The purpose of this study was to examine the clinical significance of preexisting low levels of class I DSAs in flow cytometry cross match (FC CM) negative first kidney transplant recipients (KTRs). METHODS: All of the KTRs (n=41) had low levels of anti-class I antibodies only. The kidney transplant outcome was evaluated by the development of a deleterious effect (DE) in recipients in the study cohort (Group 1: DE+, Group 2: DE-). Positivity for DE was determined based on the following criteria: biopsy proven transplant glomerulopathy (TG), de novo development of DSAs, increasing MFI values for preexisting DSAs, and the development of biopsy proven AMR. Anti-HLA antibodies were tested using single antigen Luminex technology. The HLAMatchmaker computer algorithm was used for the immunogenicity analysis of antibody verified (AbVer) mismatched eplets (MME) at the HLA-A and B loci. RESULTS: The results of this study showed that the number of AbVer MME is larger (P=0.03) in the group of KTR who developed DE. We also demonstrated that the number of AbVer MME is a strong predictor of post-transplant DE. These results indicate that persistent weakly reactive DSA is not a significant risk factor for the development of post-transplant DE and that recipients with such antibodies can be successfully transplanted. CONCLUSIONS: Immunogenicity of AbVer MME at HLA-A and B loci is strong predictor of post-transplant increases of the MFI values of preexisting or de novo developed DSA in the FC CM negative first KTR. Avoiding of transplants with more than eleven Class I AbVer MMEs may be the optimal approach to reduce the risk of kidney graft failure.

OPO Strategies to Prevent Unintended Use of Kidneys Exported for High PRA (>98% cPRA) Recipients.

Since the advent of the Kidney Allocation System (KAS), matched candidates with high (>98%) panel reactive antibody (hPRA) are given priority over local candidates with lower PRA. This often leads to exporting of kidneys. Data for these kidneys are not detailed on routine reports. Twenty-two organ procurement organizations prospectively submitted data from August 2015 to July 2016, describing allocation practices of kidneys to hPRA patients and outcomes of these kidneys. Five hundred twenty out of 6924 procured kidneys were exported for hPRA recipients. Of these, 402 (77.3%) were transplanted into the intended recipient (IR); 100 (19.2%) were transplanted into unintended recipients (UR), and 18 (3.5%) were discarded. The most common reason for use in an UR was a positive crossmatch (XM) (63%). The most common reasons for discard were donor quality (44%) and ischemic time (39%). Prior to kidney export, when tissue crossmatching was done, 96.2% of the kidneys went to the IR, versus 80.7% following virtual CM, versus 56.7% when no crossmatching was performed (p < 0.0001). A significant number of kidneys exported for hPRA patients are not being used in the IR or are being discarded. The most common reason for this is positive tissue XM. We report that unintended use of the kidney was minimized when tissue was shipped and XM results were known prior to exporting the kidney.

Effect of Treatment With Tabalumab, a B Cell-Activating Factor Inhibitor, on Highly Sensitized Patients With End-Stage Renal Disease Awaiting Transplantation.

B cell-activation factor (BAFF) is critical for B cell maturation. Inhibition of BAFF represents an appealing target for desensitization of sensitized end-stage renal disease (ESRD) patients. We conducted a Phase 2a, single-arm, open-label exploratory study investigating the effect of tabalumab (BAFF inhibitor) in patients with ESRD and calculated panel reactive antibodies (cPRAs) >50%. The treatment period duration was 24 weeks. Eighteen patients received tabalumab, at doses of 240-mg subcutaneous (SC) at Week 0 followed by 120-mg SC monthly for 5 additional months. Patients were followed for an additional 52 weeks. Immunopharmacologic effects were characterized through analysis of blood for HLA antibodies, BAFF concentrations, immunoglobulins, T and B cell subsets, as well as pre- and posttreatment tonsil and bone marrow biopsies. Significant reductions in cPRAs were observed at Weeks 16 (p = 0.043) and 36 (p = 0.004); however, absolute reductions were small (<5%). Expected pharmacologic changes in B cell subsets and immunoglobulin reductions were observed. Two tabalumab-related serious adverse events occurred (pneumonia, worsening of peripheral neuropathy), while the most common other adverse events were injection-site pain and hypotension. Three patients received matched deceased donor transplants during follow-up. Treatment with a BAFF inhibitor resulted in statistically significant, but not clinically meaningful reduction in the cPRA from baseline (NCT01200290, Clinicaltrials.gov).

Allograft Pancreatectomy: Indications and Outcomes.

This study evaluated the indications, surgical techniques, and outcomes of allograft pancreatectomy based on a single center experience. Between 2003 and 2013, 47 patients developed pancreas allograft failure, excluding mortality with a functioning pancreas allograft. Early graft loss (within 14 days) occurred in 16, and late graft loss in 31. All patients with early graft loss eventually required allograft pancreatectomy. Nineteen of 31 patients (61%) with late graft loss underwent allograft pancreatectomy. The main indication for early allograft pancreatectomy included vascular thrombosis with or without severe pancreatitis, whereas one recipient required urgent allograft pancreatectomy for gastrointestinal hemorrhage secondary to an arterioenteric fistula. In cases of late allograft pancreatectomy, graft failure with clinical symptoms such as abdominal discomfort, pain, and nausea were the main indications (13/19 [68%]), simultaneous retransplantation without clinical symptoms in 3 (16%), and vascular catastrophes including pseudoaneurysm and enteric arterial fistula in 3 (16%). Postoperative morbidity included one case each of pulmonary embolism leading to mortality, formation of pseudoaneurysm requiring placement of covered stent, and postoperative bleeding requiring relaparotomy eventually leading to femoro-femoral bypass surgery 2 years after allograftectomy. Allograft pancreatectomy can be performed safely, does not preclude subsequent retransplantation, and may be lifesaving in certain instances.

Conversion from tacrolimus to belatacept to prevent the progression of chronic kidney disease in pancreas transplantation: case report of two patients.

Belatacept is a novel immunosuppressive agent that may be used as an alternative to calcineurin inhibitors (CNI) in immunosuppression (IS) regimens. We report two cases of pancreas transplant that were switched from tacrolimus (TAC) to belatacept. Case 1: 38-year-old female with pancreas transplant alone maintained on TAC-based IS regimen whose serum creatinine (SCr) slowly deteriorated from 0.6 mg/dL at baseline to 2.2 mg/dL, 16 months posttransplant. A native kidney biopsy performed showed CNI toxicity. The patient was started on belatacept and TAC was eliminated. Case 2: 49-year-old female with simultaneous pancreas-kidney transplant, maintained on TAC-based regimen where the SCr worsened over an initial 3-month period from a baseline of 1.0 to 3.0 mg/dL. Belatacept was started and TAC was lowered. Due to persistent graft dysfunction and kidney transplant biopsy still showing changes consistent with CNI toxicity, the TAC was then discontinued. At >1 year postbelatacept and off TAC follow-up, kidney function as measured by SCr remains stable at 1.0±0.2 mg/dL in both recipients. Neither patient developed rejection following the switch, and pancreas allograft function remains stable in both recipients.

Risk factors for native kidney dysfunction in patients with abdominal multivisceral/small bowel transplantation.

Kidney dysfunction is a recognized complication after non-renal solid organ transplantation, particularly after intestinal transplant. In our study, we reviewed data on 33 multivisceral transplant (MVT)- and 15 isolated small bowel (ISB)-transplant patients to determine risk factors for kidney dysfunction. Kidney function was estimated by modified diet in renal disease (MDRD) and Schwartz formula for adults and children, respectively. Acute kidney injury (AKI) was defined as an increase in the serum Cr (sCr) greater than twofold. Kidney function declined significantly at one yr after transplantation with 46% of subjects showing an estimated GFR (eGFR) <60 mL/min. Patients with an episode of AKI were more likely to have reduced eGFR than those without AKI (p < 0.025). In linear regression analyses, age, pre-transplant sCr, eGFR at postoperative day (POD) 30, 90, 180, 270, and tacrolimus level at POD 7 showed significant correlation with one yr post-transplant eGFR (p < 0.05). Pediatric patients and patients with MVT had lesser decline in kidney function compared with adults or patients with ISB. In conclusion, risk factors for post-transplant kidney dysfunction in intestinal transplantation included age, pre-transplant sCr, AKI episode, eGFR at POD 30, 90, 180, 270, and tacrolimus level at POD 7.

Simultaneous pancreas and kidney transplantation with concurrent allograft nephrectomy for recipients with prior renal transplants lost to BK virus nephropathy: two case reports.

Candidacy for retransplantation after allograft loss due to BK virus-associated nephropathy (BKVN) with or without allograft nephrectomy is controversial. This report describes 2 renal transplant recipients who lost their grafts to BKVN and subsequently underwent simultaneous kidney and pancreas transplantation with allograft nephrectomy.

Effect of desensitization in solid organ transplant recipients depends on some cytokines genes polymorphism.

Desensitization (DS) is widely used to decrease PRA in solid organs transplant candidates (TC). Various numbers of cycles of DS are required to reduce or eliminate donor specific antibodies (DSA). The goal of this study was to investigate if there was a correlation between polymorphism (PM) of some cytokine genes and intensity of DS required to make the recipient/donor cross match compatible. Thirty-one TCs were included in the study. Antibody specificity, percent of reactive antibodies (PRA) and serum concentration of cytokines were analyzed using the LUMINEX platform. PCR-SSP method was used for IL-1alpha, IL-1beta, IL-1R, IL-1Ralpha, IL-4Ralpha, IL-12, IFNgamma, TGFbeta1, TNFalpha, IL-2, IL-4, IL-6 and IL-10 gene PM analysis. Significant relationship between PM of genes encoding IL-4Ralpha, IFNgamma and IL-12 (p70) and susceptibility to DS was demonstrated (p=0.04, p=0.01 and p=0.05 respectively). Correlation between elevated serum level of IL-12 (p70) and A/A or C/A genotype at -1188 position was found in resistant to DS TCs (p=0.015). These results indicate that analysis PM of genes encoding IL-4R, IFNgamma and IL-12 enables to define the DS strategy in TCs more accurately regarding the number of plasmapheresis (PP) cycles and dose of intravenous immunoglobulin (IVIG).

Immediate retransplantation for pancreas allograft thrombosis.

Early pancreas allograft failure most commonly results from thrombosis and requires immediate allograft pancreatectomy. Optimal timing for retransplantation remains undefined. Immediate retransplantation facilitates reuse of the same anatomic site before extensive adhesions have formed. Some studies suggest that early retransplantation is associated with a higher incidence of graft loss. This study is a retrospective review of immediate pancreas retransplants performed at a single center. All cases of pancreas allograft loss within 2 weeks were examined. Of 228 pancreas transplants, 12 grafts were lost within 2 weeks of surgery. Eleven of these underwent allograft pancreatectomy for thrombosis. One suffered anoxic brain injury and was not a retransplantation candidate, one was retransplanted at 3.5 months and nine patients underwent retransplantation 1-16 days following the original transplant. Of the nine early retransplants, one pancreas was lost to heparin-induced thrombocytopenia, one recipient died with function at 2.9 years and the other grafts continue to function at 76-1137 days (mean 572 days). One-year graft survival for early retransplantation was 89% compared to 91% for all pancreas transplants at our center. Immediate retransplantation following pancreatic graft thrombosis restores durable allograft function with outcomes comparable to first-time pancreas transplantation.

Use of self-operated auditory prompts to decrease aberrant behaviors in students with moderate mental retardation.

We examined the effectiveness of self-operated auditory prompts when used to decrease the off-task and aberrant behaviors of two students with moderate mental retardation. Its purpose was to determine if self-operated auditory prompts could be effectively used by these individuals to decrease their off-task and aberrant behaviors in work settings and during transitional times between settings. A multiple-probe across settings design with a reversal and replication was used to evaluate the effectiveness of the self-operated auditory prompting system on aberrant student behaviors in school and community settings. Previous findings were replicated in this study that demonstrate that stimulus control can be achieved through the use of self-operated auditory prompts, and demonstrates that these prompts can serve to occasion a decrease in aberrant behaviors when used by individuals with moderate mental retardation in school and community settings.

Use of self-operated auditory prompts by workers with moderate mental retardation to transition independently through vocational tasks.

The use of single- and multiple-word self-operated auditory prompting systems by five school-age workers with moderate mental retardation to independently transition between an ordered chain of tasks was examined in two vocational settings. The effectiveness of single- and multiple-word self-operated auditory prompts was assessed using an alternating treatment design within a multiple probe across settings. Analysis of the data revealed a significant effect on the number of independent task changes made by workers when using the single- or multiple-word auditory prompting system. When prompting systems were compared with one another, no significant differences were found in the number of independent task changes made by workers. Self-operated auditory prompts served as the stimulus control for desired behavior, they were effective for teaching workers with moderate mental retardation to manage their own task change behavior, and their use generalized across settings without additional training.

Maintenance of adequate hemodialysis access. Prevention of neointimal hyperplasia.

The maintenance of adequate hemodialysis vascular access is frequently complicated in the patient with polytetrafluoroethylene (PTFE) A-V hemodialysis grafts by venous anastomotic stenosis. This stenosis is caused by neointimal hyperplasia (NIH), a response to vascular injury. In this study, the authors prospectively analyzed the effect of a short-term regimen consisting of administration of two medications, heparin and low molecular weight dextran, on the development of NIH at the venous anastomosis in 79 patients with PTFE A-V hemodialysis grafts. In addition, they evaluated other parameters' effects on the development of NIH. In comparison with control subjects, heparin had some effect in minimizing the development of NIH in the PTFE grafts when evaluated radiologically at 3 months, although this effect was not statistically significant. Low molecular weight dextran, however, had no trend or statistically significant effect on this venous anastomotic narrowing. Interestingly, patient age, use of calcium channel blockers, and presence of diabetes mellitus (DM) all appeared to affect the development of NIH. Increasing age and use of calcium channel blockers was associated with decreased development of NIH; conversely, DM was associated with worsened NIH. In evaluation of access survival (time to first access failure), degree of venous anastomosis stenosis at 3 months was not predictive. Patient time on dialysis pre graft placement was the only measured parameter related to access failure. The method of dialysis pre graft placement (hemodialysis versus peritoneal dialysis) was not a significant factor in early access failure. Pharmacologic treatment of venous anastomotic narrowing in PTFE hemodialysis grafts due to NIH continues to be difficult. Short-term treatment with the tested medication failed to statistically affect NIH. Patient age, use of calcium channel blockers, and presence of DM were all factors in the development of NIH. Of measured parameters, time on dialysis pre graft placement was the only factor correlated with early access failure. In future treatment regimens, one should consider more prolonged treatment. In addition, noted risk factors should be considered when determining type of renal replacement therapy.

A prescription model for peritoneal dialysis.

The authors have developed a mathematical model for peritoneal dialysis, based on the Popovich-Pyle-Moncrief approach, that is capable of predicting urea Kt/V and total weekly creatinine clearance for a variety of peritoneal dialysis therapies. This prescription model incorporates both diffusive and convective solute removal as well as ultrafiltration and lymphatic absorption. The primary input to the model is a single peritoneal equilibration test. Twenty-four hour dialysate collection is not required. Results from an extensive prospective clinical study performed with 100 patients at five dialysis centers indicate that the model is valid for predicting urea Kt/V and creatinine clearance for continuous ambulatory peritoneal dialysis and continuous cycling peritoneal dialysis. Predicted clearances agree with the clinical data from these patients to within an average difference of approximately 10%. This model promises to be a powerful tool to assist nephrologists in quantifying the amount of peritoneal dialysis delivered by a given prescription, tailoring it to individual patient needs, and investigating the potential efficacy of a variety of alternative therapies.

Comparison of diagnostic accuracy with carbon dioxide versus iodinated contrast material in the imaging of hemodialysis access fistulas.

PURPOSE: Imaging of dialysis fistulas was performed with use of carbon dioxide and iodinated contrast material. Images were then compared to assess the quality and accuracy of CO2 as a contrast agent. PATIENTS AND METHODS: Thirty-two patients underwent digital subtraction imaging of the fistulas performed with both iodinated contrast material and CO2 to evaluate the venous anastomosis. The images were blinded and the degree of stenosis was graded in 10% increments by two physicians. Statistical analysis including sensitivity, specificity, and accuracy of CO2 images was performed. RESULTS: There was no significant difference in physician ratings of the degree of venous stenosis (P > .30). Estimation of the degree of stenosis was significantly higher with CO2 than with ionic contrast material (P = .0001). When iodinated contrast material is used as the gold standard, the sensitivity, specificity, and accuracy of CO2 were 94%, 58%, and 75%, respectively. CONCLUSIONS: CO2 has a role as a contrast agent in the imaging of dialysis access grafts when the use of iodinated contrast material is of concern. CO2 is safe for venous injections; however, it should not be used to evaluate the arterial anastomosis with the "reflux technique."

Initial clinical experience with a new model of mass transfer for peritoneal dialysis.

A clinical pilot study compared predictions of a new model of peritoneal dialysis mass transfer to measured weekly KT/V urea (KTu/V) and weekly creatinine clearance (Ccr) in liters per 1.73 m2 in 50 patients from five centers (40 CAPD, 10 CCPD). The Robertson et al. model is unique in that it does not require a 24-hour collection of dialysate. Instead, model predictions are based on the results of a standard 4-hour peritoneal equilibration test (PET) and appropriate demographic data. Analysis revealed 12 collection errors, 8 affecting the PET and 4 affecting 24-hour dialysate volume. PET drainage volume was low in six cases, excessive in two; 24-hour volume was incomplete in three, excessive in one. Similar errors were not found in the remaining 38 patients. In the 38 patients with correctly performed PET and dialysate collections, agreement between predicted and measured values was excellent.

Self-administration of epoetin beta by peritoneal dialysis patients.

Recombinant human erythropoietin (epoetin) reverses the anemia of end stage renal disease. Benefits have been evaluated primarily in hemodialysis patients because of the ease of administration via existing intravenous access. Studies are under way to evaluate the feasibility of subcutaneous self-administration of epoetin in continuous ambulatory peritoneal dialysis (CAPD) patients. Preliminary study results, using the maintenance of target hemoglobin levels to measure success and a case study demonstrate the practicality of subcutaneous self-administration of epoetin in CAPD patients.

Treatment of Pseudomonas infections in peritoneal dialysis patients.

Pseudomonas species infections in the peritoneal dialysis population consist primarily of peritonitis or exit site infections. These organisms have traditionally proven difficult to eradicate, and the standard antibiotic regimen has carried the potential for nephrotoxicity. At our institution, all peritoneal dialysis patients with Pseudomonas exit site infections or peritonitis were treated with an antibiotic combination of intraperitoneal ceftazidime and oral ciprofloxacin. Treatment duration was dependent upon the site of infection. Recurrent exit site infections were treated with a repeated course of the antibiotics, and with surgical debridement and subsequent shaving of the external cuff of double-cuffed catheters. We saw a total of 11 Pseudomonas aeruginosa exit site infections in 7 patients (4 recurrent). Patients with recurrent infections were subsequently cured with the regimen as outlined above. Of 7 patients with Pseudomonas species peritonitis (aeruginosa, fluorescens, stutszeri, and maltophilia), 5 were cured with the initial antibiotic regimen. The 2 failures were both infected with Pseudomonas maltophilia, which is consistent with observed organism sensitivity data. The combination of ceftazidime and ciprofloxacin with the option for surgical debridement of the external cuff (in exit site infections) appears effective in the treatment of Pseudomonas species infections in the peritoneal dialysis population. Sensitivity data should be used to adjust the antibiotic regimen when appropriate.

Clinical experiences with a single use Y bagless CAPD system applying a quick disconnect clamp for external occlusion.

The Single Use Y set is a disposable CAPD system that incorporates the use of a Quick Disconnect Clamp (QDC) for external occlusion. The system is designed using two types of twist lock connectology. The twist lock bag connector located at the distal end of the set is designed with a flange that provides a safety shelf for proper hand position during bag connection. The proximal patient connector on the Y set is a twist lock design requiring placement of povidone-iodine in the disinfectant chamber of the connector prior to patient connection. The Single Use Y is discarded after use.

Unusual presentation of pulmonary edema in a hemodialysis patient.

Despite the technical advances made during the last several years, chronic dialysis still is plagued by continuing problems. Intermittent volume overload is one of the most common. The radiologic evidence of pulmonary edema can be confusing in the end-stage renal disease population. The following case illustrates a hemodialysis patient with pulmonary edema whose initial chest x-ray appeared more consistent with metastatic malignancy.