Dual kidney transplants from adult marginal donors successfully expand the limited deceased donor organ pool.

BACKGROUND: The need to expand the organ donor pool remains a formidable challenge in kidney transplantation (KT). The use of expanded criteria donors (ECDs) represents one approach, but kidney discard rates are high because of concerns regarding overall quality. Dual KT (DKT) may reduce organ discard and optimize the use of kidneys from marginal donors. STUDY DESIGN: We conducted a single-center retrospective review of outcomes in adult recipients of DKTs from adult marginal deceased donors (DD) defined by limited renal functional capacity. If the calculated creatinine clearance in an adult DD was <65 mL/min, then the kidneys were transplanted as a DKT. RESULTS: Over 11.5 yr, 72 DKTS were performed including 45 from ECDs, 17 from donation after cardiac death (DCD) donors, and 10 from standard criteria donors (SCD). Mean adult DD and recipient ages were both 60 yr, including 29 DDs and 26 recipients ≥65 yr of age. Mean pre-DKT waiting and dialysis vintage times were 12 months and 25 months, respectively. Actual patient and graft survival rates were 84.7% and 70.8%, respectively, with a mean follow-up of 58 months. One yr and death-censored graft survival rates were 90% and 80%, respectively. Outcomes did not differ by DD category, recipient age, or presence of delayed graft function (DGF). Eleven patients died at a mean of 32 months post-DKT (eight with functioning grafts) and 13 other patients experienced graft losses at a mean of 33 months. The incidence of DGF was 25%; there were two cases (2.8%) of primary non-function. Mean length of initial hospital stay was 7.2 d. Mean serum creatinine and glomerular filtration rate levels at 12 and 24 months were 1.5 and 53 and 1.5 mg/dL and 51 mL/min/1.73 m(2) , respectively. DKT graft survival and function were superior to concurrent single ECD and similar to concurrent SCD KTs. Two patients underwent successful kidney retransplantation, so the dialysis-free rate in surviving patients was 87%. The proportion of total renal function transplanted from adult DD to DKT recipients was 77% compared to 56% for patients receiving single KTs. CONCLUSIONS: Dual kidney transplantation using kidneys from adult marginal DDs that otherwise might be discarded offer a viable option to counteract the growing shortage of acceptable single kidneys. Excellent medium-term outcomes can be achieved and waiting times can be reduced in a predominantly older recipient population.

The Human Pancreas as a Source of Protolerogenic Extracellular Matrix Scaffold for a New-generation Bioartificial Endocrine Pancreas.

OBJECTIVES: Our study aims at producing acellular extracellular matrix scaffolds from the human pancreas (hpaECMs) as a first critical step toward the production of a new-generation, fully human-derived bioartificial endocrine pancreas. In this bioartificial endocrine pancreas, the hardware will be represented by hpaECMs, whereas the software will consist in the cellular compartment generated from patient's own cells. BACKGROUND: Extracellular matrix (ECM)-based scaffolds obtained through the decellularization of native organs have become the favored platform in the field of complex organ bioengineering. However, the paradigm is now switching from the porcine to the human model. METHODS: To achieve our goal, human pancreata were decellularized with Triton-based solution and thoroughly characterized. Primary endpoints were complete cell and DNA clearance, preservation of ECM components, growth factors and stiffness, ability to induce angiogenesis, conservation of the framework of the innate vasculature, and immunogenicity. Secondary endpoint was hpaECMs' ability to sustain growth and function of human islet and human primary pancreatic endothelial cells. RESULTS: Results show that hpaECMs can be successfully and consistently produced from human pancreata and maintain their innate molecular and spatial framework and stiffness, and vital growth factors. Importantly, hpaECMs inhibit human naïve CD4 T-cell expansion in response to polyclonal stimuli by inducing their apoptosis and promoting their conversion into regulatory T cells. hpaECMs are cytocompatible and supportive of representative pancreatic cell types. DISCUSSION: We, therefore, conclude that hpaECMs has the potential to become an ideal platform for investigations aiming at the manufacturing of a regenerative medicine-inspired bioartificial endocrine pancreas.

Donor-derived myeloid sarcoma in two kidney transplant recipients from a single donor.

We report the rare occurrence of donor-derived myeloid sarcoma in two kidney transplant patients who received organs from a single deceased donor. There was no evidence of preexisting hematologic malignancy in the donor at the time of organ recovery. Both recipients developed leukemic involvement that appeared to be limited to the transplanted organ. Fluorescence in situ hybridization (FISH) and molecular genotyping analyses confirmed that the malignant cells were of donor origin in each patient. Allograft nephrectomy and immediate withdrawal of immunosuppression were performed in both cases; systemic chemotherapy was subsequently administered to one patient. Both recipients were in remission at least one year following the diagnosis of donor-derived myeloid sarcoma. These cases suggest that restoration of the immune system after withdrawal of immunosuppressive therapy and allograft nephrectomy may be sufficient to control HLA-mismatched donor-derived myeloid sarcoma without systemic involvement.

A Single Center 11 Year Experience with 202 Pancreas Transplants in the New Millennium: Evolving Trends.

Our single center experience with pancreas transplantation (PTx) over an 11+ year period is reviewed. METHODS: We retrospectively studied outcomes in 202 consecutive PTxs in 192 patients at our center. All patients received either rabbit anti-thymocyte globulin (rATG) or alemtuzumab (Alem) induction with tacrolimus/mycophenolate mofetil and tapered steroids or early withdrawal. 179 PTxs (89%) were performed with portal-enteric and 23 with systemic-enteric drainage. RESULTS: From 11/01 to 3/13, we performed 162 simultaneous kidney-PTxs (SKPT), 35 sequential PTxs after kidney, and 5 PTx alone (40 solitary PTxs, SPT). 186 PTxs (92%) were primary and 16 were pancreas retransplants. With a mean follow-up of 5.5 years, overall patient (86% SKPT versus 87% SPT), kidney (74% SKPT versus 80% SPT), and pancreas graft survival (both 65%) rates were comparable. Causes of PTx loss were also similar between SKPT and SPT; the rates of early thrombosis were 8.6% and 5%, respectively. Acute rejection rates were similar between groups (SKPT 29% versus SPT 28%, p= not significant). A randomized trial of Alem versus rATG induction in SKPT demonstrated lower rates of acute rejection and infection in the Alem group. Consequently, Alem induction has been used exclusively in all PTxs since 2009. Early steroid elimination has been feasible in most patients. Surveillance PTx biopsy-directed immunosuppression has contributed to equivalent long-term outcomes in SKPT and SPT. Good results have been achieved in African-American patients and in patients with a type 2 diabetes phenotype. CONCLUSIONS: Excellent 5-year outcomes following PTx can be achieved as >86% of patients are alive, >87% of surviving patients are dialysis-free, 80% of surviving patients remain insulin-free, and 88% of surviving patients have detectable C-peptide levels.

Pancreas transplantation: The Wake Forest experience in the new millennium.

AIM: To investigate the Wake Forest experience with pancreas transplantation in the new millennium with attention to surgical techniques and immunosuppression. METHODS: A monocentric, retrospective review of outcomes in simultaneous kidney-pancreas transplant (SKPT) and solitary pancreas transplant (SPT) recipients was performed. All patients underwent pancreas transplantation as intent-to-treat with portal venous and enteric exocrine drainage and received depleting antibody induction; maintenance therapy included tapered steroids or early steroid elimination with mycophenolate and tacrolimus. Recipient selection was based on clinical judgment whether or not the patient exhibited measureable levels of C-peptide. RESULTS: Over an 11.25 year period, 202 pancreas transplants were performed in 192 patients including 162 SKPTs and 40 SPTs. A total of 186 (92%) were primary and 16 (8%) pancreas retransplants; portal-enteric drainage was performed in 179 cases. A total of 39 pancreas transplants were performed in African American (AA) patients; of the 162 SKPTs, 30 were performed in patients with pretransplant C-peptide levels > 2.0 ng/mL. In addition, from 2005-2008, 46 SKPT patients were enrolled in a prospective study of single dose alemtuzumab vs 3-5 doses of rabbit anti-thymocyte globulin induction therapy. With a mean follow-up of 5.7 in SKPT vs 7.7 years in SPT recipients, overall patient (86% SKPT vs 87% SPT) and kidney (74% SKPT vs 80% SPT) graft survival rates as well as insulin-free rates (both 65%) were similar (P = NS). Although mortality rates were nearly identical in SKPT compared to SPT recipients, patterns and timing of death were different as no early mortality occurred in SPT recipients whereas the rates of mortality following SKPT were 4%, 9% and 12%, at 1-, 3- and 5-years follow-up, respectively (P < 0.05). The primary cause of graft loss in SKPT recipients was death with a functioning graft whereas the major cause of graft loss following SPT was acute and chronic rejection. The overall incidence of acute rejection was 29% in SKPT and 27.5% in SPT recipients (P = NS). Lower rates of acute rejection and major infection were evidenced in SKPT patients receiving alemtuzumab induction therapy. Comparable kidney and pancreas graft survival rates were observed in AA and non-AA recipients despite a higher prevalence of a "type 2 diabetes" phenotype in AA. Results comparable to those achieved in insulinopenic diabetics were found in the transplantation of type 2 diabetics with detectable C-peptide levels. CONCLUSION: In the new millennium, acceptable medium-term outcomes can be achieved in SKPT and SPTs as nearly 2/3rds of patients are insulin independent following pancreas transplantation.

Osseus metaplasia in kidney allografts as a paradigm of regenerative medicine principles.

We report the sixth case of osseous metaplasia that has occurred in the last 5 years, after a deceased-donor renal transplant was performed on a young man. While its clinical significance is unclear and probably irrelevant, osseous metaplasia is one of the most relevant principles of regenerative medicine, where every bodily district contains progenitor cells that can generate cells specific to the germ layer from which they come. After the Case Report, we review the literature and speculate on the underlying pathophysiology of osseous metaplasia. Available data seem to support the hypothesis that osteogenic precursor cells, inducing factors, and a suitable environment are key for osseous metaplasia.

Alternative pathway dysfunction in kidney disease: a case report and review of dense deposit disease and C3 glomerulopathy.

Dysfunction of the alternative pathway of complement activation provides a pathophysiologic link between the C3 glomerulopathies dense deposit disease and glomerulonephritis with C3 deposition and the clinically and histologically distinct atypical hemolytic uremic syndrome. Previously, dense deposit disease was known as membranoproliferative glomerulonephritis type II, but paucity or complete lack of immunoglobulin deposition on immunofluorescence staining and advances in our understanding of alternative pathway dysregulation have separated it from immune complex-mediated membranoproliferative glomerulonephritis types I and III. We discuss a case of dense deposit disease and review the current pathologic classification, clinical course, treatment options, and related conditions.

Production and implantation of renal extracellular matrix scaffolds from porcine kidneys as a platform for renal bioengineering investigations.

BACKGROUND: It is important to identify new sources of transplantable organs because of the critical shortage of donor organs. Tissue engineering holds the potential to address this issue through the implementation of decellularization-recellularization technology. OBJECTIVE: To produce and examine acellular renal extracellular matrix (ECM) scaffolds as a platform for kidney bioengineering. METHODS: Porcine kidneys were decellularized with distilled water and sodium dodecyl sulfate-based solution. After rinsing with buffer solution to remove the sodium dodecyl sulfate, the so-obtained renal ECM scaffolds were processed for vascular imaging, histology, and cell seeding to investigate the vascular patency, degree of decellularization, and scaffold biocompatibility in vitro. Four whole renal scaffolds were implanted in pigs to assess whether these constructs would sustain normal blood pressure and to determine their biocompatibility in vivo. Pigs were sacrificed after 2 weeks and the explanted scaffolds were processed for histology. RESULTS: Renal ECM scaffolds were successfully produced from porcine kidneys. Scaffolds retained their essential ECM architecture and an intact vascular tree and allowed cell growth. On implantation, unseeded scaffolds were easily reperfused, sustained blood pressure, and were tolerated throughout the study period. No blood extravasation occurred. Pathology of explanted scaffolds showed maintenance of renal ultrastructure. Presence of inflammatory cells in the pericapsular region and complete thrombosis of the vascular tree were evident. CONCLUSIONS: Our investigations show that pig kidneys can be successfully decellularized to produce renal ECM scaffolds. These scaffolds maintain their basic components, are biocompatible, and show intact, though thrombosed, vasculature.

Pancreas transplantation: lessons learned from a decade of experience at Wake Forest Baptist Medical Center.

This article reviews the outcome of pancreas transplantations in diabetic recipients according to risk factors, surgical techniques, and immunosuppression management that evolved over the course of a decade at Wake Forest Baptist Medical Center. A randomized trial of alemtuzumab versus rabbit anti-thymocyte globulin (rATG) induction in simultaneous kidney-pancreas transplantation (SKPT) at our institution demonstrated lower rates of acute rejection and infection in the alemtuzumab group. Consequently, alemtuzumab induction has been used exclusively in all pancreas transplantations since February 2009. Early steroid elimination has been feasible in the majority of patients. Extensive experience with surveillance pancreas biopsies in solitary pancreas transplantation (SPT) is described. Surveillance pancreas biopsy-directed immunosuppression has contributed to equivalent long-term pancreas graft survival rates in SKPT and SPT recipients at our center, in contrast to recent registry reports of persistently higher rates of immunologic pancreas graft loss in SPT. Furthermore, the impact of donor and recipient selection on outcomes is explored. Excellent results have been achieved with older (extended) donors and recipients, in recipients of organs from donation after cardiac death donors managed with extracorporeal support, and in African-American patients. Type 2 diabetics with detectable C-peptide levels have been transplanted successfully with outcomes comparable to those of insulinopenic diabetics. Our experiences are discussed in the light of findings reported in the literature.

Coincident idiopathic focal segmental glomerulosclerosis collapsing variant and diabetic nephropathy in an African American homozygous for MYH9 risk variants.

Familial clustering of disparate kidney diseases including clinically diagnosed hypertensive and diabetic nephropathy, idiopathic focal segmental glomerulosclerosis, and HIV-associated nephropathy are often observed in African Americans. Admixture mapping recently identified the nonmuscle myosin heavy chain 9 gene (MYH9) as a susceptibility factor strongly associated with several nondiabetic etiologies of end-stage renal disease in African Americans, less strongly with diabetes-associated end-stage renal disease. MYH9-associated nephropathies reside in the spectrum of focal segmental glomerulosclerosis/focal global glomerulosclerosis. The renal histology in proteinuric African Americans homozygous for MYH9 risk variants with longstanding type 2 diabetes mellitus is unknown. We report a case of coincident idiopathic focal segmental glomerulosclerosis collapsing variant and diabetic nephropathy in an African American homozygous for the MYH9 E1 risk haplotype. This case demonstrates that diabetic African Americans with overt proteinuria can have mixed renal lesions, including those in the spectrum of MYH9-associated nephropathy. Careful interpretation of kidney biopsies in proteinuric African Americans with diabetes is necessary to exclude coincident nondiabetic forms of nephropathy, precisely define etiologies of kidney disease, and determine the natural history and treatment response in mixed lesions of diabetes-associated and MYH9-associated kidney disease.

Glomerulocystic kidney: one hundred-year perspective.

CONTEXT: Glomerular cysts, defined as Bowman space dilatation greater than 2 to 3 times normal size, are found in disorders of diverse etiology and with a spectrum of clinical manifestations. The term glomerulocystic kidney (GCK) refers to a kidney with greater than 5% cystic glomeruli. Although usually a disease of the young, GCK also occurs in adults. OBJECTIVE: To assess the recent molecular genetics of GCK, review our files, revisit the literature, and perform in silico experiments. DATA SOURCES: We retrieved 20 cases from our files and identified more than 230 cases published in the literature under several designations. CONCLUSIONS: Although GCK is at least in part a variant of autosomal dominant or recessive polycystic kidney disease (PKD), linkage analysis has excluded PKD-associated gene mutations in many cases of GCK. A subtype of familial GCK, presenting with cystic kidneys, hyperuricemia, and isosthenuria is due to uromodullin mutations. In addition, the familial hypoplastic variant of GCK that is associated with diabetes is caused by mutations in TCF2, the gene encoding hepatocyte nuclear factor-1beta. The term GCK disease (GCKD) should be reserved for the latter molecularly recognized/inherited subtypes of GCK (not to include PKD). Review of our cases, the literature, and our in silico analysis of the overlapping genetic entities integrates established molecular-genetic functions into a proposed model of glomerulocystogenesis; a classification scheme emerged that (1) emphasizes the clinical significance of glomerular cysts, (2) provides a pertinent differential diagnosis, and (3) suggests screening for probable mutations.

A randomized trial of alemtuzumab versus antithymocyte globulin induction in renal and pancreas transplantation.

BACKGROUND.: Alemtuzumab and rabbit antithymocyte globulin (rATG) are commonly used for induction of immunsuppression for kidney and pancreas transplantation, but the two agents have not been compared directly. METHODS.: We conducted a prospective randomized single-center trial comparing alemtuzumab and rATG induction in adult kidney and pancreas transplantation in patients treated with similar maintenance immunosuppression. RESULTS.: Between February 1, 2005, and September 1, 2007, 222 patients randomly received either alemtuzumab (n=113) or rATG (n=109) induction; 180 (81%) underwent kidney alone, 38 (17%) simultaneous pancreas-kidney, and 4 (2%) pancreas after kidney transplants. Of 180 kidney-alone transplants, 152 (84%) were from deceased donors, including 61 (34%) from expanded criteria donors. Retransplantation, human leukocyte antigen match, antibody titer, expanded criteria donors, race, cytomegalovirus status, delayed graft function, and immunologic risks were similar between the two induction groups. With a median follow-up of 2 years (minimum 1 year), overall patient, kidney, and pancreas graft survival rates were 96%, 89%, and 90%, respectively. Survival, initial length of stay, and maintenance immunosuppression (including early steroid elimination) were similar between alemtuzumab and rATG groups, but biopsy-proven acute rejection (BPAR) episodes occurred in 16 (14%) alemtuzumab patients compared with 28 (26%) rATG patients (P=0.02). Late BPAR (>12 months after transplant) occurred in 1 (8%) alemtuzumab patient and 3 (11%) rATG patients (P=NS). Infections and malignancy were similar between the two induction arms. CONCLUSION.: Alemtuzumab and rATG induction therapies were equally safe, but alemtuzumab was associated with less BPAR.

Distribution of pathologic findings in individuals with nephrotic proteinuria according to serum albumin.

BACKGROUND: Previous studies of the nephrotic syndrome have not carefully examined the relationship between serum albumin and the distribution of pathologic diagnoses found at the time of biopsy. The spectrum of pathologic findings in individuals with nephrotic proteinuria and a normal serum albumin has not been determined. Knowledge regarding the spectrum of findings in nephrotic proteinuria according to serum albumin levels may help nephrologists in the clinical decision making of when to perform a renal biopsy and in determining proper management of these patients. METHODS: Pathologic reports of native kidney biopsies performed for idiopathic proteinuria >3 g/24 h were reviewed. Clinical characteristics and biopsy findings were compared for individuals with serum albumin <30 g/L (Group I), 30 to <35 g/L (Group II) and >/=35 g/L (Group III). RESULTS: There were 57 patients in Group I, 20 in Group II and 35 in Group III. The proportion of individuals with focal and segmental glomerulosclerosis (FSGS) increased according to group: 26% in Group I, 45% in Group II and 74% in Group III. Of 35 patients in Group III, 34 had FSGS or advanced nephrosclerosis from another cause. Seven of 17 Group III patients with follow-up required dialysis after a mean interval of 6 years. Few of these patients received immunosuppressive therapy. CONCLUSIONS: As serum albumin increases in the nephrotic syndrome, the proportion of patients with FSGS increases. Patients with nephrotic proteinuria and a serum albumin >35 g/L suffer from FSGS, nephrosclerosis and have poor renal survival. When evaluating nephrotic patients, nephrologists should use this knowledge about the spectrum of disease in the clinical decision making of when to perform a biopsy and in providing the patient more precise information regarding risks, benefits and alternatives of the kidney biopsy procedure.

Experience with deceased donor kidney transplantation in 114 patients over age 60.

BACKGROUND: In the recent past, advanced age was a contraindication to kidney transplantation (KT). The purpose of this study was to review retrospectively our single center experience in deceased donor (DD) KT with respect to recipient age. METHODS: From 10/1/01 to 9/1/06, we performed 356 adult DD KTs. Patients received antibody induction in combination with tacrolimus, mycophenolate mofetil, and tapered steroids. RESULTS: A total of 114 (32%) patients were greater than 60 (including 25 >70 years), 186 (52%) were 40-59 years of age, and 56 (16%) were 19-39 years of age. Of the 114 older patients, 61 (54%) received KTs from expanded criteria DDs (ECD), more than the younger age groups (39% ECDs in patients 40-59 years versus 18% ECDs in patients 19-39 years, P < .0001). Mean waiting time (21 mo) was less for patients greater than 60 years compared with the other 2 groups combined (29 mo, P = .06). Patient survival was 91% in recipients greater than 60 years compared with 95% in those less than 60 years of age (P = NS) with a mean follow-up of 27 mo. Graft survival was similar for all 3 age groups (82% >60 years vs 83% in patients 40-59 years vs 87% in patients 19-39 years, P = NS). Initial and subsequent graft function, morbidity, and resource use were similar among groups. Patient survival [93% ECD vs 89% standard criteria DDs (SCD), P = NS) and graft survival (82% ECD vs 81% SCD, P = NS) rates were similar, whereas mean waiting times (18 mo ECD vs 25 mo SCD, P = .04) were less in patients greater than 60 years who received ECD KTs compared with patients greater than 60 years who received SCD KTs. CONCLUSIONS: Patients greater than 60 years account currently for one third of DD KTs performed at our center, and more than half receive kidneys from ECDs. By preferentially directing ECD kidneys to appropriately selected elderly patients, waiting times can be decreased and survival is similar compared with SCD KTs in the elderly. In addition, short-term outcomes can be achieved in patients greater than 60 years that are comparable with those in younger patients.

Recurring translocation (10;17) and deletion (14q) in clear cell sarcoma of the kidney.

CONTEXT: Clear cell sarcoma of the kidney (CCSK) is a prognostically unfavorable renal neoplasm of childhood. Previous cytogenetic studies of CCSK have reported balanced translocations t(10;17)(q22;p13) and t(10;17)(q11;p12). Although the tumor suppressor gene p53 is located at the chromosome 17p13 breakpoint, p53 abnormalities are rarely present in these tumors. OBJECTIVE: To identify cytogenetic abnormalities in CCSK and correlate these findings with other clinicopathologic parameters. DESIGN: A retrospective review of CCSK patients from 1990 to 2005 was conducted at our medical center. We performed clinical and histologic review, p53 immunohistochemical and classic cytogenetics (or ploidy analysis), and p53 fluorescence in situ hybridization analyses. RESULTS: Five male patients (age range, 6 months to 4 years) were identified with cytogenetic abnormalities. Of 3 cytogenetically informative cases, one revealed a clonal balanced translocation t(10;17)(q22;p13) and an interstitial deletion of chromosome 14, del(14)(q24.1q31.1), and the other 2 patients had normal karyotypes. Fluorescence in situ hybridization for p53 in the t(10;17) case revealed no deletion. Immunohistochemical evaluation of p53 demonstrated lack of nuclear protein accumulation in all cases. CONCLUSIONS: Together with the published literature, our results indicate that translocation (10;17) and interstitial deletions of chromosome 14q are recurring cytogenetic lesions in CCSK. To date, 3 cases of CCSK or "sarcomatoid Wilms tumors" have been reported to exhibit t(10;17). One previously reported case of CCSK contained deletion 14q. Results of p53 immunohistochemistry and/or p53 fluorescence in situ hybridization in this report suggest lack of mutations or deletions of this tumor suppressor in these CCSK cases. The t(10;17) breakpoint and deletion of chromosome 14q24 suggest that other genes are involved in tumor pathogenesis.

Experience with dual kidney transplants from donors at the extremes of age.

BACKGROUND: Dual kidney transplantation (DKT) from donors at the extremes of age represents one approach to expanding the organ donor pool. The purpose of this study was to review our experience with DKT from older donors and en bloc KT (EBKT) from small pediatric donors. METHODS: Deceased donor KTs performed at our center between October 2001 and November 2005, were reviewed retrospectively. If the calculated creatinine clearance in an expanded criteria donor was <65 mL/min, then the kidneys were transplanted dually into a single adult recipient. If a pediatric donor weighed <15 kg, then the kidneys were transplanted en bloc. In both instances, low-risk recipients were chosen (primary transplant, low sensitization, body mass index <25 kg/m(2), human leukocyte antigen matching). Donor, recipient, and transplant characteristics, waiting time, and outcomes were examined. RESULTS: Of a total of 279 deceased donor KTs during the 49-month study period, 15 (5%) recipients underwent DKT and 5 (2%) underwent EBKT. Mean donor age was 65.4 years and 21.4 months in the DKT and EBKT groups, respectively. Patient survival rates in both groups were 100% with a mean follow-up of 22 months (minimum, 6 months). Kidney graft survival rates were 80% (12/15) and 60% (3/5) in the DKT and EBKT groups, respectively. The combined incidence of delayed graft function was 10%. Mean 12-month glomerular filtration rates were 46 mL/min and 66 mL/min in the DKT and EBKT groups, respectively. CONCLUSIONS: DKT using kidneys from marginal elderly donors and EBKT from small pediatric donors appear to offer a viable option to counteract the shortage of acceptable kidney donors.

Intermediate-term outcomes with expanded criteria deceased donors in kidney transplantation: a spectrum or specter of quality?

OBJECTIVE: To compare intermediate-term outcomes in adult recipients of expanded criteria (ECD) versus concurrent standard criteria (SCD) deceased donor kidney transplants at a single center using a standardized approach. SUMMARY BACKGROUND DATA: Expanded criteria donors (ECDs) are a source of kidneys that increase the donor organ pool, but the value of transplanting these kidneys has been questioned because of concerns regarding diminished survival and predicted poorer intermediate-term outcomes. METHODS: Over a 47-month period, we performed 244 deceased donor kidney transplants into adult recipients, including 143 from SCDs and 101 from ECDs. Management algorithms were implemented to preserve nephron function, and recipient selection for an ECD kidney transplant was based on low immunologic risk. All patients received depleting antibody induction in combination with tacrolimus and mycophenolate mofetil. A total of 188 patients (77%) had at least a 1-year follow-up. RESULTS: ECDs were older, had a higher BMI, had an increased incidence of cerebrovascular brain death and preexisting donor hypertension, and had a lower estimated creatinine clearance (CrCl, all P < 0.01) compared with SCDs. Cold ischemic times were similar between groups, but more ECD kidneys were preserved with pulsatile perfusion (P < 0.01). ECD kidney recipients were older, less sensitized, had a lower BMI, had fewer 0-antigen mismatches, and had a shorter waiting time (all P < 0.01) compared with SCD kidney recipients. Actual patient (93%) and kidney graft (83%) survival rates were similar between groups with a mean follow-up of 24 months. The rates of delayed graft function (DGF), acute rejection, readmissions, operative complications, major infections, and resource utilization were comparable between groups. Renal function followed longitudinally was consistently better in SCD patients (P < 0.05). Black recipients had higher rates of DGF, acute rejection, and graft loss (P < 0.05), but the effects were less pronounced in the ECD group. CONCLUSIONS: By appropriate donor and recipient profiling and the use of management algorithms to project and protect renal function, excellent intermediate-term outcomes can be achieved with ECD kidney transplants that are comparable to SCD kidney transplants.

Optimal use of older donors and recipients in kidney transplantation.

BACKGROUND: The aging donor and recipient population have led to new challenges in kidney transplantation. The purpose of this study was to review retrospectively our single center experience in deceased-donor kidney transplantation, with respect to donor and recipient age. METHODS: From October 1, 2001, through February 20, 2004, we performed 144 deceased-donor kidney transplantations, which included 37 procedures (26%) in recipients > or =60 years old and 107 procedures (74%) in recipients 19 to 59 years old. The deceased-donor pool included 57 expanded criteria donors (ECD) and 87 standard criteria donors (defined as not ECD). ECD kidneys were used by matching estimated renal functional mass to recipient size (body mass index, <25 kg/m(2)), which included the use of dual kidney transplantations (n = 9). ECD kidney recipients were further selected on the basis of age >40 years and low immunologic risk. Recipients received rabbit antithymocyte globulin or alemtuzumab induction in combination with tacrolimus, mycophenolate mofetil, and steroids. RESULTS: The mean age differed between recipient groups (65 vs 46 years; P < .001). In recipients > or =60 years old, 23 recipients (62%) received kidney transplants from ECDs compared with 34 kidney transplants from ECDs (32%; P < .001) in recipients who were <60 years old. Patient survival was 89% in recipients who were > or =60 years old, compared with 95% in recipients who were <60 years old (P = .11), with a mean follow-up time of 27 months. Kidney graft survival rates were 84% in both recipient groups. Initial and subsequent graft function, rejection, infection, reoperation, length of stay, readmission, and resource use were similar among groups. CONCLUSION: By the matching of nephron mass with recipient size and avoiding the use of ECD kidneys in recipients with a high immunologic risk, short-term outcomes that are comparable with standard criteria donor kidneys in younger patients can be achieved with either older donors or recipients, regardless of age.

Clinico-pathologic findings in medullary cystic kidney disease type 2.

Medullary cystic kidney disease type 2 is an uncommon autosomal dominant condition characterized by juvenile onset hyperuricemia, precocious gout and chronic renal failure progressing to end-stage renal disease in the 4th through 7th decades of life. A family suffering from this condition is described. The patient in the index case presented with renal insufficiency as a child. A renal biopsy revealed tubular atrophy, and immunohistochemical staining of the tissue for uromodulin (Tamm Horsfall protein) revealed dense deposits in renal tubular cells. Genetic testing revealed a single nucleotide mutation (c.899G>A) resulting in an exchange of a cysteine residue for tyrosine (C300Y). Medullary cystic kidney disease type 2 (also known as uromodulin-associated kidney disease) likely represents a form of endoplasmic reticulum storage disease, with deposition of the abnormal uromodulin protein in the endoplasmic reticulum, leading to tubular cell atrophy and death.

Neuroblastoma in an adult.

Neuroblastoma is extremely rare in adults. Advances in classification and therapy have been recently made by an analysis of pediatric tumors. We present the case of a 39-year-old man who had Stage 1 neuroblastoma with unfavorable histologic features that was treated with surgery only. Neuroblastoma should be considered as a diagnosis for adult patients with a suprarenal mass and, if confirmed, neuroblastoma in adults should be classified and treated according to pediatric guidelines.