Single vs dual (en bloc) kidney transplants from donors ≤ 5 years of age: A single center experience.

AIM: To compare outcomes between single and dual en bloc (EB) kidney transplants (KT) from small pediatric donors. METHODS: Monocentric nonprospective review of KTs from pediatric donors ≤ 5 years of age. Dual EB KT was defined as keeping both donor kidneys attached to the inferior vena cava and aorta, which were then used as venous and arterial conduits for the subsequent transplant into a single recipient. Donor age was less useful than either donor weight or kidney size in decision-making for kidney utilization as kidneys from donors < 8 kg or kidneys < 6 cm in length were not transplanted. Post-transplant management strategies were standardized in all patients. RESULTS: From 2002-2015, 59 KTs were performed including 34 dual EB and 25 single KTs. Mean age of donors (17 mo vs 38 mo, P < 0.001), mean weight (11.0 kg vs 17.4 kg, P = 0.046) and male donors (50% vs 84%, P = 0.01) were lower in the dual EB compared to the single KT group, respectively. Mean cold ischemia time (21 h), kidney donor profile index (KDPI; 73% vs 62%) and levels of serum creatinine (SCr, 0.37 mg/dL vs 0.49 mg/dL, all P = NS) were comparable in the dual EB and single KT groups, respectively. Actuarial graft and patient survival rates at 5-years follow-up were comparable. There was one case of thrombosis resulting in graft loss in each group. Delayed graft function incidence (12% dual EB vs 20% single KT, P = NS) was slightly lower in dual EB KT recipients. Initial duration of hospital stay (mean 5.4 d vs 5.6 d) and the one-year incidences of acute rejection (6% vs 16%), operative complications (3% vs 4%), and major infection were comparable in the dual EB and single KT groups, respectively (all P = NS). Mean 12 mo SCr and abbreviated MDRD levels were 1.17 mg/dL vs 1.35 mg/dL and 72.5 mL/min per 1.73 m(2) vs 60.5 mL/min per 1.73 m(2) (both P = NS) in the dual EB and single KT groups, respectively. CONCLUSION: By transplanting kidneys from young pediatric donors into adult recipients, one can effectively expand the limited donor pool and achieve excellent medium-term outcomes.

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.

Immunotactoid Glomerulopathy and Cryoglobulinemic Nephropathy: Two Entities with Many Similarities. A Unified Conceptual Approach.

Immunotactoid glomerulopathy is a rare disorder that has been characterized at the ultrastructural level. Due to its rarity, there are few comprehensive studies relating to this disorder. Electron microscopy essentially characterizes this disease. The glomerular electron dense deposits which are typical of this condition consist of aggregates of highly organized microtubular structures of various diameters, but generally measuring 30-50 nm in width with a propensity to dispose themselves in parallel bundles intersecting in different planes. This study compares a large series of patients with cryoglobulinemic nephropathy with a series of patients with immunotactoid glomerulopathy to address whether there may be similarities that warrant considering these two entities part of a spectrum. This study reviews the clinicopathologic features of both entities and emphasizes ultrastructural findings that characterize them. Significant immunomorphologic overlap was found when these two disorders were compared in this study. There were also striking similarities in clinical presentation/behavior, laboratory findings and prognosis. Proteomic analysis has also demonstrated similar spectra for both entities. We postulate that immunotactoid glomerulopathy and cryoglobulinemic nephropathy are part of the spectrum of renal manifestations in patients with circulating cryoglobulins and renal disease.

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.

Pancreas transplantation in C-peptide positive patients: does "type" of diabetes really matter?

BACKGROUND: In the past, type 2 (C-peptide positive) diabetes mellitus (DM) was a contraindication for simultaneous pancreas-kidney transplantation (SPKT). STUDY DESIGN: We retrospectively analyzed outcomes in SPKT recipients according to pretransplantation C-peptide levels ≥ 2.0 ng/mL or < 2.0 ng/mL. RESULTS: From November 2001 to March 2013, we performed 162 SPKTs including 30 (18.5%) in patients with C-peptide levels ≥ 2.0 ng/mL pretransplantation (C-peptide positive group, range 2.1 to 12.4 ng/mL) and 132 in patients with absent or low C-peptide levels (<2.0 ng/mL, C-peptide "negative"). C-peptide positive patients were older at SPKT, had a later age of onset and shorter duration of pretransplantation DM, and more were African-American (all p < 0.05) compared with C-peptide negative patients. With a mean follow-up of 5.6 years, patient (80% vs 82.6%), kidney graft (63.3% vs 68.9%), and pancreas graft survivals (50% vs 62.1%, all p = NS) rates were comparable in C-peptide positive and negative patients, respectively. At latest follow-up, there were no differences in acute rejection episodes, surgical complications, major infections, readmissions, hemoglobin A1c levels, serum creatinine, and estimated glomerular filtration rate levels between the 2 groups. C-peptide levels were higher (mean 5.0 vs 2.6 ng/mL, p < 0.05) and post-transplant weight gain (≥ 5 kg) was more common (57% vs 33%, p = 0.004) in the C-peptide positive group. Survival outcomes in C-peptide positive (n = 14) vs C-peptide negative (n = 22) African-American patients were similar, as were outcomes in C-peptide positive patients with a body mass index < or ≥ 28 kg/m(2). CONCLUSIONS: Patients with higher pretransplantion C-peptide levels appear to have a type 2 DM phenotype compared to insulinopenic patients undergoing SPKT. However, survival and functional outcomes were similar, suggesting that pretransplantation C-peptide levels should not be used exclusively to determine candidacy for SPKT.

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.

Influence of recipient age on deceased donor kidney transplant outcomes in the expanded criteria donor era.

METHODS: We performed a retrospective single-center review of 884 deceased donor (DD) kidney transplants (KTs) in patients (pts) aged ≥40 yr. RESULTS: One hundred and four (11.8%) pts were ≥70 (mean 74), 286 (32.3%) were 60-69 (mean 64), and 494 (55.9%) were 40-59 (mean 51) yr of age; the proportion receiving expanded criteria donor (ECD) kidneys were 66%, 49%, and 30%, respectively (p < 0.001). Mean waiting time (15 months) was shorter for pts ≥70 yr compared to the other two groups combined (23 months, p = 0.002). With mean follow-up ranging from 54 to 70 months, actual pt (81% vs. 72%, p = 0.002) and graft (66% vs. 58.5%, p = 0.03) survival rates were higher in the younger compared to the two older groups, whereas death-censored graft survival was similar (76% vs. 73%, p = NS). The incidence of death with a functioning graft correlated with older recipient age group, increasing from 13% to 18% to 23% (p = 0.01). The incidence of delayed graft function was similar (31.8% overall), and renal function, morbidity, and resource utilization were similar among groups. CONCLUSIONS: By directing ECD kidneys to selected older pts, waiting times are reduced and censored survival outcomes are similar to middle-aged patients, suggesting that matching strategies for graft and patient lifespan are warranted.

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.

Discarded human kidneys as a source of ECM scaffold for kidney regeneration technologies.

In the United States, more than 2600 kidneys are discarded annually, from the total number of kidneys procured for transplant. We hypothesized that this organ pool may be used as a platform for renal bioengineering and regeneration research. We previously showed that decellularization of porcine kidneys yields renal extracellular matrix (ECM) scaffolds that maintain their basic components, support cell growth and welfare in vitro and in vivo, and show an intact vasculature that, when such scaffolds are implanted in vivo, is able to sustain physiological blood pressure. The purpose of the current study was to test if the same strategy can be applied to discarded human kidneys in order to obtain human renal ECM scaffolds. The results show that the sodium dodecylsulfate-based decellularization protocol completely cleared the cellular compartment in these kidneys, while the innate ECM framework retained its architecture and biochemical properties. Samples of human renal ECM scaffolds stimulated angiogenesis in a chick chorioallantoic membrane assay. Importantly, the innate vascular network in the human renal ECM scaffolds retained its compliance. Collectively, these results indicate that discarded human kidneys are a suitable source of renal scaffolds and their use for tissue engineering applications may be more clinically applicable than kidneys derived from animals.

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.

Is collapsing C1q nephropathy another MYH9-associated kidney disease? A case report.

C1q nephropathy is a rare kidney disease that can present with nephrotic syndrome and typically has the histologic phenotype of either minimal change disease or focal segmental glomerulosclerosis (FSGS). Disagreement exists about whether it is a distinct immune complex-mediated glomerulopathy or it resides in the spectrum of FSGS-minimal change disease. Two African American patients with C1q nephropathy histologically presenting as the collapsing variant of FSGS (collapsing C1q nephropathy) and rapid loss of kidney function were genotyped for polymorphisms in the non-muscle myosin heavy chain 9 gene (MYH9). Both cases were homozygous for the MYH9 E1 risk haplotype, the variant strongly associated with idiopathic FSGS, collapsing FSGS in human immunodeficiency virus-associated nephropathy, and focal global glomerulosclerosis (historically attributed to hypertensive nephrosclerosis). Collapsing C1q nephropathy with rapid progression to end-stage renal disease appears to reside in the MYH9-associated disease spectrum.

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.

Experience in renal and extrarenal transplantation with donation after cardiac death donors with selective use of extracorporeal support.

BACKGROUND: Most reports of donation after cardiac death (DCD) donors are exclusive to kidney transplantation and report high rates of delayed graft function (DGF). STUDY DESIGN: From April 1, 2003, to October 3, 2007, we performed 53 kidney transplantations and 4 simultaneous kidney-pancreas transplantations from DCD donors. All DCD donor kidneys were managed with pulsatile perfusion preservation, and all simultaneous kidney-pancreas transplantation donors were managed with extracorporeal support. RESULTS: Of 53 DCD kidney transplantations, 44 (83%) were from standard criteria donors (SCD) and 9 (17%) from expanded criteria donors (ECD). With a mean followup of 12 months, actual patient and kidney graft survival rates were 94% and 87%, respectively. Patient and graft survival rates were 100% in the 4 simultaneous kidney-pancreas transplantations. Incidence of DGF was 57% (60% without versus 20% with extracorporeal support, p = 0.036). Comparison of the 53 DCD donor kidney transplantations with 316 concurrent donation after brain death (DBD) donor adult kidney transplantations (178 SCD, 138 ECD) revealed no differences in demographics or outcomes, except that the DCD donor group had fewer ECDs (17% DCD versus 44% DBD; p = 0.0002), fewer 0-antigen mismatch kidney transplantations (7.5% DCD versus 19% DBD; p = 0.05), and more kidneys preserved with pulsatile perfusion (100% DCD versus 52% DBD; p < 0.0001). Incidences of DGF (57% DCD versus 19% DBD; p < 0.0001) and acute rejection (19% DCD versus 10% DBD; p = 0.10) were higher in the DCD donor group, which resulted in a longer initial length of stay (mean 11 days DCD versus 8.0 days DBD; p = 0.006). CONCLUSIONS: Despite a high incidence of DGF in the absence of extracorporeal support and greater initial resource use, comparable short-term results can be achieved with DCD and DBD donor kidney transplantations.

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.