Post-transplantation nephroptosis causing recurrent episodes of acute renal failure and hypertension secondary to intermittent vascular torsion of intraperitoneal renal allograft.

Nephroptosis is a rare complication in renal transplantation, but one with significant associated risk. Due to non-specific clinical features, there may be a substantial delay in diagnosis and loss of the transplanted kidney due to renal pedicle thrombosis. We present a case of post-transplantation nephroptosis after simultaneous pancreas and kidney transplant, which resulted in accelerated hypertension and reversible acute kidney injury >1 year after transplantation. Prompt detection of this rare entity leading to expeditious surgical intervention is necessary to preserve viability of the renal allograft.

Invasive squamous cell bladder cancer of the ureterovesical junction in a renal transplant patient: a case report.

It is well established in the literature that the incidence of malignancy is higher in transplant patients than in the general population. Risk factors and screening guidelines for transplant patients have been proposed, but are far from standardized. In this case report, we discuss the treatment course of a 73-year-old female with a history of renal tuberculosis, who developed squamous cell carcinoma at the transplant ureterovesical junction 6 years following graft placement. To our knowledge, this is the second reported case in a patient with a history of renal tuberculosis.

A Nationwide Analysis of Kidney Autotransplantation.

There are limited data regarding outcomes of patients underwent kidney autotransplantation. This study aims to investigate outcomes of such patients. The nationwide inpatient sample database was used to identify patients underwent kidney autotransplantation during 2002 to 2012. Multivariate analyses using logistic regression were performed to investigate morbidity predictors. A total of 817 patients underwent kidney autotransplantation from 2002 to 2012. The most common indication of surgery was renal artery pathology (22.7%) followed by ureter pathology (17%). Overall, 97.7 per cent of operations were performed in urban teaching hospitals. The number of procedures from 2008 to 2012 were significantly higher compared with the number of them from 2002 to 2007 (473 vs 345, P < 0.01). The overall mortality and morbidity of patients were 1.3 and 46.2 per cent, respectively. The most common postoperative complications were transplanted kidney failure (10.7%) followed by hemorrhagic complications (9.7%). Obesity [adjusted odds ratio (AOR): 9.62, P < 0.01], fluid and electrolyte disorders (AOR: 3.67, P < 0.01), and preoperative chronic kidney disease (AOR: 1.80, P = 0.03) were predictors of morbidity in patients. In conclusion, Kidney autotransplantation is associated with low mortality but a high morbidity rate. The most common indications of kidney autotransplantation are renal artery and ureter pathologies, respectively. A kidney transplant failure rate of 10.7 per cent was observed in patients with kidney autotransplantation. The most common postoperative complication was hemorrhagic in nature.

Immunological Challenges Facing Translation of Alginate Encapsulated Porcine Islet Xenotransplantation to Human Clinical Trials.

Transplantation of alginate-encapsulated islets has the potential to treat patients suffering from type I diabetes, a condition characterized by an autoimmune attack against insulin-secreting beta cells. However, there are multiple immunological challenges associated with this procedure, all of which must be adequately addressed prior to translation from trials in small animal and nonhuman primate models to human clinical trials. Principal threats to graft viability include immune-mediated destruction triggered by immunogenic alginate impurities, unfavorable polymer composition and surface characteristics, and release of membrane-permeable antigens, as well as damage associated molecular patterns (DAMPs) by the encapsulated islets themselves. The lack of standardization of significant parameters of bioencapsulation device design and manufacture (i.e., purification protocols, surface-modification grafting techniques, alginate composition modifications) between labs is yet another obstacle that must be overcome before a clinically effective and applicable protocol for encapsulating islets can be implemented. Nonetheless, substantial progress is being made, as is evident from prolonged graft survival times and improved protection from immune-mediated graft destruction reported by various research groups, but also with regard to discoveries of specific pathways involved in explaining observed outcomes. Progress in the latter is essential for a comprehensive understanding of the mechanisms responsible for the varying levels of immunogenicity of certain alginate devices. Successful translation of encapsulated islet transplantation from in vitro and animal model testing to human clinical trials hinges on application of this knowledge of the pathways and interactions which comprise immune-mediated rejection. Thus, this review not only focuses on the different factors contributing to provocation of the immune reaction by encapsulated islets, but also on the defining characteristics of the response itself.

Hand-Assisted Laparoscopic Donor Nephrectomy in Complete Situs Inversus.

Complete situs inversus is a rare congenital anomaly characterized by transposition of organs. We report a case of renal transplantation using a kidney from a living complete situs inversus donor. The recipient was a 59-year-old female with end-stage renal disease because of type 2 diabetes mellitus. The donor was the 56-year-old sister of the recipient with complete situs inversus. CT angiogram of the abdomen and pelvis showed complete situs inversus and an otherwise normal appearance of the bilateral kidneys with patent bilateral single renal arteries and longer renal vein in the right kidney. The patient was taken to the operating room for a hand-assisted laparoscopic right donor nephrectomy. The patient tolerated the procedure well and was discharged home in good condition on postoperative day 1. The recipient experienced no episodes of acute rejection or infection, with serum creatinine levels of 0.8-1.2 mg/dL. Laparoscopic donor nephrectomy in a patient with complete situs inversus remains a technically feasible operation and the presence of situs inversus should not preclude consideration for living kidney donation.

Kidney transplantation in obese patients.

The World Health Organization estimated that in 2014, over 600 million people met criteria for obesity. In 2011, over 30% of individuals undergoing kidney transplant had a body mass index (BMI) 35 kg/m(2) or greater. A number of recent studies have confirmed the relationship between overweight/obesity and important comorbidities in kidney transplant patients. As with non-transplant surgeries, the rate of wound and soft tissue complications are increased following transplant as is the incidence of delayed graft function. These two issues appear to contribute to longer length of stay compared to normal BMI. New onset diabetes after transplant and cardiac outcomes also appear to be increased in the obese population. The impact of obesity on patient survival after kidney transplantation remains controversial, but appears to mirror the impact of extremes of BMI in non-transplant populations. Early experience with (open and laparoscopic) Roux-en-Y gastric bypass and laparoscopic sleeve gastrectomy support excellent weight loss (in the range of 50%-60% excess weight lost at 1 year), but experts have recommended the need for further studies. Long term nutrient deficiencies remain a concern but in general, these procedures do not appear to adversely impact absorption of immunosuppressive medications. In this study, we review the literature to arrive at a better understanding of the risks related to renal transplantation among individuals with obesity.

Total pancreatectomy and islet autotransplantation: A decade nationwide analysis.

AIM: To investigate outcomes and predictors of in-hospital morbidity and mortality after total pancreatectomy (TP) and islet autotransplantation. METHODS: The nationwide inpatient sample (NIS) database was used to identify patients who underwent TP and islet autotransplantation (IAT) between 2002-2012 in the United States. Variables of interest were inherent variables of NIS database which included demographic data (age, sex, and race), comorbidities (such as diabetes mellitus, hypertension, and deficiency anemia), and admission type (elective vs non-elective). The primary endpoints were mortality and postoperative complications according to the ICD-9 diagnosis codes which were reported as the second to 25(th) diagnosis of patients in the database. Risk adjusted analysis was performed to investigate morbidity predictors. Multivariate regression analysis was used to identify predictors of in-hospital morbidity. RESULTS: We evaluated a total of 923 patients who underwent IAT after pancreatectomy during 2002-2012. Among them, there were 754 patients who had TP + IAT. The most common indication of surgery was chronic pancreatitis (86%) followed by acute pancreatitis (12%). The number of patients undergoing TP + IAT annually significantly increased during the 11 years of study from 53 cases in 2002 to 155 cases in 2012. Overall mortality and morbidity of patients were 0% and 57.8 %, respectively. Post-surgical hypoinsulinemia was reported in 42.3% of patients, indicating that 57.7% of patients were insulin independent during hospitalization. Predictors of in-hospital morbidity were obesity [adjusted odds ratio (AOR): 3.02, P = 0.01], fluid and electrolyte disorders (AOR: 2.71, P < 0.01), alcohol abuse (AOR: 2.63, P < 0.01), and weight loss (AOR: 2.43, P < 0.01). CONCLUSION: TP + IAT is a safe procedure with no mortality, acceptable morbidity, and achieved high rate of early insulin independence. Obesity is the most significant predictor of in-hospital morbidity.

Impact of donor age and weaning status on pancreatic exocrine and endocrine tissue maturation in pigs.

BACKGROUND: During the process of islet isolation, pancreatic enzymes are activated and released, adversely affecting islet survival and function. We hypothesize that the exocrine component of pancreases harvested from pre-weaned juvenile pigs is immature and hence pancreatic tissue from these donors is protected from injury during isolation and prolonged tissue culture. METHODS: Biopsy specimens taken from pancreases harvested from neonatal (5-10 days), pre-weaned juvenile (18-22 days), weaned juvenile (45-60 days), and young adult pigs (>90 days) were fixed and stained with hematoxylin and eosin. Sections were examined under a fluorescent microscope to evaluate exocrine zymogen fluorescence intensity (ZFI) and under an electron microscope to evaluate exocrine zymogen granule density (ZGD). RESULTS: Exocrine content estimation showed significantly lower ZFI and ZGD in juvenile pig pancreases (1.5 ± 0.04 U/µm(2) , ZFI; 1.03 ± 0.07 × 10(3) /100 µm(2) , ZGD) compared to young adult pigs (2.4 ± 0.05U/µm(2) , ZFI; 1.53 ± 0.08 × 10(3) /100 µm(2) ZGD). Islets in juvenile pig pancreases were on average smaller (105.2 ± 11.2 µm) than islets in young adult pigs (192 ± 7.7 µm), but their insulin content was comparable (80.9 ± 2.2% juvenile; 84.2 ± 0.3% young adult, P > 0.05). All data expressed as mean ± SEM. CONCLUSION: Porcine islet xenotransplantation continues to make strides toward utilization in clinical trials of type 1 diabetes. Porcine donor age and weaning status influence the extent of exocrine maturation of the pancreas. Juvenile porcine pancreases may represent an alternative donor source for islet xenotransplantation as their exocrine component is relatively immature; this preserves islet viability during extended tissue culture following isolation.

The effect of Nrf2 pathway activation on human pancreatic islet cells.

BACKGROUND: Pancreatic islets are known to contain low level of antioxidants that renders them vulnerable to oxidative stress. Nrf2 is the master regulator of numerous genes, encoding antioxidant, detoxifying, and cytoprotective molecules. Activation of Nrf2 pathway induces up-regulation of numerous genes encoding antioxidant and phase II detoxifying enzymes and related proteins. However, little is known regarding the role of this pathway in human islet cells. The aim was to investigate the effect of Nrf2 activator (dh404, CDDO-9,11-dihydro-trifluoroethyl amide) on human islet cells. METHODS: Human islets were obtained from cadaveric donors. After dh404 treatment, Nrf2 translocation, mRNA expression, and protein abundance of its key target gene products were examined. The proportion of dh404-treated or non-treated viable islet beta cells was analyzed using flowcytemetry. The cytoprotective effects against oxidative stress and production of inflammatory mediators, and in vivo islet function after transplantation were determined. RESULTS: Nrf2 nuclear translocation was confirmed by con-focal microscope within 2 hours after treatment, which was associated with a dose-dependent increase in mRNA expression of anti-oxidants, including NQO1, HO-1, and GCLC. Enhanced HO-1 expression in dh404 treated islets was confirmed by Western Blot assay. Islet function after transplantation (2000 IEQ/mouse) to diabetic nude mice was not affected with or without dh404 treatment. After induction of oxidative stress with hydrogen peroxide (200 µM) the proportion of dh404-treated viable islet cells was significantly higher in the dh404-treated than untreated islets (74% vs.57%; P<0.05). Dh404 significantly decreased production of cytokines/chemokines including IL-1ß, IL-6, IFN-γ and MCP-1. CONCLUSION: Treatment of human pancreatic islets with the potent synthetic Nrf2 activator, dh404, significantly increased expression of the key anti-oxidants enzymes, decreased inflammatory mediators in islets and conferred protection against oxidative stress in beta cells.

Juvenile porcine islets can restore euglycemia in diabetic athymic nude mice after xenotransplantation.

BACKGROUND: Porcine islet xenotransplantation has been demonstrated in many animal studies to cure experimentally induced diabetes. However, several issues currently impede the translation of porcine islet xenotransplantation to sustained insulin independence clinically. Although adult pigs have mature islets that secrete insulin in response to a glucose challenge, and are physiologically similar to humans, there are logistical considerations with adult porcine tissue that are not present with juvenile porcine tissue. To circumvent these issues, we have identified 18- to 21-day-old preweaned juvenile pigs as islet donors as we have previously demonstrated superior islet yields and function from juvenile pigs using our islet isolation protocols. METHODS: We evaluated the efficacy of islets isolated from 18- to 24-day-old Yorkshire swine in vitro using a standard glucose-stimulated insulin response assay, and in vivo after xenotransplantation under the kidney capsule of streptozotocin-induced 8- to 10-week-old male athymic nude mice. The mice were monitored for a period of 60 days after transplantation, after which the grafts were explanted and analyzed. RESULTS: Diabetic athymic nude mice transplanted with 1500 to 3000 islet equivalents (IEq) of islets achieved sustained normoglycemia for up to 60 days after islet transplantation. When the grafts were explanted with the kidney, a rapid return to hyperglycemia was observed. CONCLUSIONS: Efficacy and dose-titration studies evaluating these islets in immunocompetent and nonobese diabetic mouse models are underway. The results of these studies will permit application for nonhuman primate and pivotal clinical trials in human diabetic patients in the near future.

Treatment With Dimethyl Fumarate Attenuates Calcineurin Inhibitor-induced Nephrotoxicity.

BACKGROUND: Cyclosporine A (CsA) is an immunosuppressive drug which has been widely used to prevent rejection after organ transplantation. However, its therapeutic use is limited by nephrotoxicity, in part mediated by oxidative stress. The present study aims to investigate the protective effects of dimethyl fumarate (DMF) on CsA-induced nephrotoxicity by enhancing the antioxidant defense system. METHODS: Male Sprague-Dawley rats were treated with CsA (n = 8, 20 mg/kg per day intraperitoneally) or CsA + DMF (n = 7, 50 mg/kg per day orally) for 28 days. Renal function, histopathology, malondialdehyde (MDA), myeloperoxidase levels, and antioxidant enzyme expression were determined. RESULTS: The DMF cotreatment ameliorated CsA-induced renal dysfunction as evidenced by significant decrease in serum creatinine (CsA 0.79 ± 0.02 mg/dL vs CsA + DMF 0.62 ± 0.04 mg/dL, P = 0.001) and urea (CsA 66.9 ± 0.4 mg/dL vs CsA + DMF 53.3 ± 2.6 mg/dl, P < 0.0001) levels, as well as improvement of creatinine clearance. Dimethyl fumarate also significantly decreased serum MDA and renal tissue MDA and myeloperoxidase contents. The protein expression of NAD(P)H quinone oxidoreductase-1, a major cellular antioxidant and detoxifying enzyme, was significantly enhanced by DMF administration in kidney. CONCLUSIONS: Administration of DMF has a protective potential against CsA nephrotoxicity. The protection afforded by DMF is mediated in part through inhibiting oxidative stress and inflammation and enhancing the antioxidant capacity.

Pharmacological activation of Nrf2 pathway improves pancreatic islet isolation and transplantation.

Oxidative stress is a major cause of islet damage and loss during the islet isolation process. The Nrf2 pathway plays a critical role in protecting the cells against oxidative stress. The aim of this study was to investigate the effect of an Nrf2 activator (dh404) on islet isolation and transplantation in a rodent model. Islet isolation was conducted using Nrf2-deficient and wild-type mice and vehicle-treated and Nrf2 activator (dh404)-treated rats. Islet yield, viability, and Nrf2 pathway activity were determined. An in vivo islet potency test was done. Islet yield and viability in Nrf2-deficient mice was significantly lower compared to wild-type (p < 0.05) mice. Furthermore, administration of dh404 to normal Sprague-Dawley rats enhanced nuclear translocation of Nrf2 and elevated HO-1 expression in the pancreas. Islet yield and viability in dh404-treated rats was significantly higher compared to the vehicle-treated group (p < 0.05). The diabetes cure rate in nude mice with chemically induced diabetes was significantly greater in those transplanted with islets from the dh404-treated group (6/9) than vehicle-treated rats (2/9, p < 0.05). The Nrf2 pathway plays a significant role in protecting islets against stress caused by the isolation process. Pharmacological activation of the Nrf2 pathway significantly increased HO-1 expression, improved islet yield, viability, and function after transplantation.

Islet and stem cell encapsulation for clinical transplantation.

Over the last decade, improvements in islet isolation techniques have made islet transplantation an option for a certain subset of patients with long-standing diabetes. Although islet transplants have shown improved graft function, adequate function beyond the second year has not yet been demonstrated, and patients still require immunosuppression to prevent rejection. Since allogeneic islet transplants have experienced some success, the next step is to improve graft function while eliminating the need for systemic immunosuppressive therapy. Biomaterial encapsulation offers a strategy to avoid the need for toxic immunosuppression while increasing the chances of graft function and survival. Encapsulation entails coating cells or tissue in a semipermeable biocompatible material that allows for the passage of nutrients, oxygen, and hormones while blocking immune cells and regulatory substances from recognizing and destroying the cell, thus avoiding the need for systemic immunosuppressive therapy. Despite advances in encapsulation technology, these developments have not yet been meaningfully translated into clinical islet transplantation, for which several factors are to blame, including graft hypoxia, host inflammatory response, fibrosis, improper choice of biomaterial type, lack of standard guidelines, and post-transplantation device failure. Several new approaches, such as the use of porcine islets, stem cells, development of prevascularized implants, islet nanocoating, and multilayer encapsulation, continue to generate intense scientific interest in this rapidly expanding field. This review provides a comprehensive update on islet and stem cell encapsulation as a treatment modality in type 1 diabetes, including a historical outlook as well as current and future research avenues.

In vitro maturation of viable islets from partially digested young pig pancreas.

Isolation of islets from market-sized pigs is costly, with considerable islet losses from fragmentation occurring during isolation and tissue culture. Fetal and neonatal pigs yield insulin unresponsive islet-like cell clusters that become glucose-responsive after extended periods of time. Both issues impact clinical applicability and commercial scale-up. We have focused our efforts on a cost-effective scalable method of isolating viable insulin-responsive islets. Young Yorkshire pigs (mean age 20 days, range 4-30 days) underwent rapid pancreatectomy (<5 min) and partial digestion using low-dose collagenase, followed by in vitro culture at 37°C and 5% CO2 for up to 14 days. Islet viability was assessed using FDA/PI or Newport Green, and function was assessed using a glucose-stimulated insulin release (GSIR) assay. Islet yield was performed using enumeration of dithizone-stained aliquots. The young porcine (YP) islet yield at dissociation was 12.6 ± 2.1 × 10(3) IEQ (mean ± SEM) per organ and increased to 33.3 ± 6.4 × 10(3) IEQ after 7 days of in vitro culture. Viability was 97.3 ± 7% at dissociation and remained over 90% viable after 11 days in tissue culture (n = ns). Glucose responsiveness increased throughout maturation in culture. The stimulation index (SI) of the islets increased from 1.7 ± 2 on culture day 3 to 2.58 ± 0.5 on culture day 7. These results suggest that this method is both efficient and scalable for isolating and maturing insulin-responsive porcine islets in culture.

Noninvasive evaluation of the vascular response to transplantation of alginate encapsulated islets using the dorsal skin-fold model.

Alginate encapsulation reduces the risk of transplant rejection by evading immune-mediated cell injury and rejection; however, poor vascular perfusion results in graft failure. Since existing imaging models are incapable of quantifying the vascular response to biomaterial implants after transplantation, in this study, we demonstrate the use of in vivo laser speckle imaging (LSI) and wide-field functional imaging (WiFI) to monitor the microvascular environment surrounding biomaterial implants. The vascular response to two islet-containing biomaterial encapsulation devices, alginate microcapsules and a high-guluronate alginate sheet, was studied and compared after implantation into the mouse dorsal window chamber (N = 4 per implant group). Images obtained over a 14-day period using LSI and WiFI were analyzed using algorithms to quantify blood flow, hemoglobin oxygen saturation and vascular density. Using our method, we were able to monitor the changes in the peri-implant microvasculature noninvasively without the use of fluorescent dyes. Significant changes in blood flow, hemoglobin oxygen saturation and vascular density were noted as early as the first week post-transplant. The dorsal window chamber model enables comparison of host responses to transplanted biomaterials. Future experiments will study the effect of changes in alginate composition on the vascular and immune responses.

Association of pre-transplant blood pressure with post-transplant outcomes.

BACKGROUND: Previous studies have indicated U-shaped associations between blood pressure (BP) and mortality in dialysis patients. We hypothesized that a similar association exists between pre-transplant BP and post-transplant outcomes in dialysis patients who undergo successful kidney transplantation. METHODS: Data from the Scientific Registry of Transplant Recipients were linked to the five-yr cohort of a large dialysis organization in the United States. We identified all dialysis patients who received a kidney transplant during this period. Unadjusted and multivariate adjusted predictors of transplant outcomes were examined. RESULTS: A total of 13 881 patients included in our study were 47 ± 14 yr old and included 42% women. There was no association between pre-transplant systolic BP and post-transplant mortality, although a decreased risk trend was observed in those with low post-dialysis systolic BP. Compared to patients with pre-dialysis diastolic BP 70 to <80 mmHg, patients with pre-dialysis diastolic BP <50 mmHg experienced lower risk of post-transplant death (hazard ratios [HR]: 0.74, 95% CI: 0.55-0.99). However, compared to patients with post-dialysis diastolic BP 70 to <80 mmHg, patients with post-dialysis diastolic BP ≥100 mmHg experienced higher risk of death (HR: 3.50, 95% CI: 1.57-7.84). In addition, very low (<50 mmHg for diastolic BP and <110 mmHg for systolic BP) pre-transplant BP was associated with lower risk of graft loss. CONCLUSIONS: Low post-dialysis systolic BP and low pre-dialysis diastolic BP are associated with lower post-transplant risk of death, whereas very high post-dialysis diastolic BP is associated with higher mortality in kidney transplant recipients. BP variations in dialysis patients prior to kidney transplantation may have a bearing on post-transplant outcome, which warrants additional studies.

Colorectal surgery in kidney transplant recipients: a decade of trends and outcomes in the United States.

There is paucity of data evaluating the trends and outcomes of colorectal surgery (CRS) in kidney transplant recipients (KTRs). Using the Nationwide Inpatient Sample 2001 to 2010, a retrospective review of CRS performed in KTRs was performed. Trends, demographics, indications, and outcomes were examined for elective and emergent cases and compared with the general population (GP) on multivariate logistic regression. A total of 2616 KTRs underwent CRS, 50 per cent of which were done emergently. KTRs developed colon and rectal cancer at a younger age and had significantly higher incidence of comorbidities compared with the GP. Diverticular disease was the most common indication for surgery (48%) followed by cancer (30.6%). Compared with the GP, KTRs had higher rates of mortality (6.29 vs 3.64%), wound complications (8.02 vs 5.37%), and acute renal failure (ARF) (17.14 vs 7.10%) (all P < 0.05). No difference was seen in the incidence of anastomotic leak. On multivariate analysis, KTRs had higher associated odds of ARF (odds ratio, 2.02; P < 0.001), whereas the odds of mortality, wound, and anastomotic complications were similar to the GP. Emergency surgery in KTRs was associated with worse outcomes compared with the elective setting. KTRs undergoing CRS have unique characteristics that are different than the GP. They are at an increased risk of complications, especially acute renal failure.

Timing of return to dialysis in patients with failing kidney transplants.

In the last decade, the number of patients starting dialysis after a failed kidney transplant has increased substantially. These patients appear to be different from their transplant-naïve counterparts, and so may be the timing of dialysis therapy initiation. An increasing number of studies suggest that in transplant-naïve patients, later dialysis initiation is associated with better outcomes. Very few data are available on timing of dialysis reinitiation in failed transplant recipients, and they suggest that an earlier return to dialysis therapy tended to be associated with worse survival, especially among healthier and younger patients and women. Failed transplant patients may also have unique issues such as continuation of immunosuppression versus withdrawal or the need for remnant allograft nephrectomy with regard to dialysis reinitiation. These patients may have a different predialysis preparation work-up, worse blood pressure control, higher or lower serum phosphorus levels, lower serum bicarbonate concentration, and worse anemia management. The choice of dialysis modality may also represent an important question for these patients, even though there appears to be no difference in mortality between patients starting peritoneal versus hemodialysis. Finally, failed transplant patients returning to dialysis appear to have a higher mortality rate compared with transplant-naïve incident dialysis patients, especially in the first several months of dialysis therapy. In this review, we will summarize the available data related to the timing of dialysis initiation and outcomes in failed kidney transplant patients after returning to dialysis.

Achieving donor management goals before deceased donor procurement is associated with more organs transplanted per donor.

BACKGROUND: There is a national shortage of organs available for transplantation. Implementation of preset donor management goals (DMGs) to improve outcomes is recommended, but uniform practices and data are lacking. We hypothesized that meeting DMGs before organ procurement would result in more organs transplanted per donor (OTPD). METHODS: The eight organ procurement organization in United Network for Organ Sharing Region 5 selected 10 critical care end points as DMGs. Each organ procurement organization submitted retrospective data from 40 standard criteria donors. "DMGs met" was defined as achieving any eight DMGs before procurement. The primary outcome was ≥4 OTPD. Binary logistic regression was used to determine independent predictors of ≥4 OTPD with a p<0.05. RESULTS: Three hundred twenty standard criteria donors had 3.6±1.6 OTPD. Donors with DMGs met had more OTPD (4.4 vs. 3.3, p<0.001) and were more likely to have ≥4 OTPD (70% vs. 39%, p<0.001). Independent predictors of ≥4 OTPD were age (odds ratio [OR]=0.94), serum creatinine (OR=0.65), thyroid hormone use (OR=2.0), "DMGs met" (OR=4.4), and achieving the following individual DMGs: central venous pressure 4 mm Hg to 10 mm Hg (OR=1.9), ejection fraction>50% (OR=4.0), Pao2:FIO2>300 (OR=4.6), and serum sodium 135 to 160 mEq/L (OR=3.4). CONCLUSIONS: Meeting DMGs before procurement resulted in more OTPD. Donor factors and critical care end points are independent predictors of organ yield. Prospective studies are needed to determine the true impact of each DMG on the number and function of transplanted organs.