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.

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.

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.

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.

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.

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.

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.

Dual kidney transplantation: a case-control comparison with single kidney transplantation from standard and expanded criteria donors.

BACKGROUND: The purpose of this study was to perform a case-matched cohort analysis of dual kidney transplantation (DKT) from expanded criteria donors (ECDs) compared to single kidney transplantation (SKT) from concurrent ECDs and standard criteria donors (SCDs, defined as non-ECD). METHODS: Deceased donor (DD) kidney transplants (KTs) performed at a single center between October 2001 and February 2006 were reviewed retrospectively. If the calculated DD creatinine clearance (CrCl) was <65 mL/min, then the kidneys were transplanted dually into a single patient. In the case of DKT and SKT from ECDs, low risk patients were chosen and informed consent was obtained. Patients in each group were matched for age, gender, race, transplant number, and time of transplant. RESULTS: Of 294 adult DD KTs performed, 16 (5%) were DKTs, which were matched with 16 concurrent SCD and 16 ECD SKT patients. Mean donor age in years (65 DKT vs. 33 SCD vs. 61 ECD; P<0.0001) and mean donor CrCl in ml/min (54 DKT vs. 91 SCD vs. 76 ECD; P=0.002) were different between groups. Patient survival was 100% in the DKT and SCD SKT groups and 94% in the ECD SKT group (mean follow up 23-28 months); graft survival rates in the DKT, SCD, and ECD groups were 81%, 81%, and 94%, respectively (P=NS). Graft function, rejection, and morbidity were similar between groups. CONCLUSIONS: DKT using kidneys from marginal ECDs is a viable option to counteract the growing shortage of available organs. Excellent short-term results and renal function can be achieved with older, low nephron mass donors provided that both kidneys are transplanted into a single recipient.

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.

Influence of pulsatile perfusion preservation on outcomes in kidney transplantation from expanded criteria donors.

BACKGROUND: Expanded criteria donors (ECDs) increase the donor organ pool, but the value of transplanting these kidneys has been questioned because of concerns about diminished survival, poorer renal function, and higher rates of delayed graft function. STUDY DESIGN: Retrospective analysis of intermediate-term outcomes in ECD kidney transplantations according to method of preservation at a single center using a standardized approach. RESULTS: Over a 5-year period, we performed 141 donations-after-brain-death ECD kidney transplantations into adult recipients. A total of 114 kidneys (81%) were managed with combined cold-storage and pulsatile perfusion preservation (PPP), and the remaining 27 (19%) were preserved with cold storage (CS). The PPP group had a higher proportion of kidneys preserved for longer than 30 hours (28% versus 0, p < 0.001) and a longer mean cold ischemia time (24.5 hours PPP versus 19 hours CS, p < 0.01). Other donor and recipient characteristics were similar between groups. Incidence of delayed graft function was 11% in PPP-stored kidneys versus 37% in CS kidneys (p = 0.002). With a mean followup of 27 months, patient (91% PPP versus 96% CS) and kidney graft survival (81% PPP versus 81.5% CS) rates were comparable. Mean 12-month serum creatinine (1.9 mg/dL) and calculated Modification of Diet in Renal Disease glomerular filtration rate (41 mL/min) values were similar between groups. CONCLUSIONS: Despite longer cold ischemia times, recipients of ECD kidneys managed with PPP had similar survival and functional outcomes, but experienced a marked reduction in the rate of delayed graft function.

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.

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.

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.

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.

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.

Acute renal failure in cystic fibrosis: association with inhaled tobramycin therapy.

We describe a 20-year-old patient with cystic fibrosis who developed acute nonoliguric renal failure associated with inhaled tobramycin. Clinical evaluation and renal biopsy findings were consistent with aminoglycoside-induced changes. Renal failure due to inhaled aminoglycosides has not been previously reported. The incidence may rise, however, with the increased use of this treatment modality. Measurable tobramycin levels due to inhalational therapy with conventional dosing in the reported patient indicate that the drug can be systemically absorbed, and renal tubular toxicity may occur.

Glomerulopathies with organized deposits.

Glomerulopathies with organized deposits are much less frequent than those with usual-type immune complex deposits, even in busy renal biopsy practices. It is important to be able to provide the correct diagnosis because of the therapeutic and prognostic implications that may follow. This goal is achieved by thoughtful consideration of all pathologic and clinical findings. This review presents the salient features of amyloidosis, cryoglobulinemic glomerulonephritis, fibrillary glomerulonephritis, immunotactoid glomerulopathy, collagenofibrotic glomerulopathy, and fibronectin glomerulopathy. We also point out matrical fibrillary deposits that may mimic some of the above entities at the ultrastructural level. Emphasis is placed, through comparative illustrations, on the prominent role of electron microscopy.

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.