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A small number of kidney transplant recipients abruptly lose function secondary to acute renal artery or vein thrombosis or more rarely a form of necrotizing vasculitis. We report a group of four kidney transplant recipients who lost... more
A small number of kidney transplant recipients abruptly lose function secondary to acute renal artery or vein thrombosis or more rarely a form of necrotizing vasculitis. We report a group of four kidney transplant recipients who lost renal function and share the following features: (1) diabetes (type I, insulin-dependent diabetes mellitus, type II or steroid-induced); (2) abrupt change/loss of renal function; (3) a concomitant clinical event (fever, viral symptoms, menometrorrhagia, viremia, bacteremia); (4) severe necrotizing vasculitis with hemorrhagic necrosis on histopathology; (5) patent renal artery and vein at time of transplant nephrectomy (i.e., no vascular thrombosis); and (6) high levels of peripheral serum gamma-IFN 1-5 days before transplant nephrectomy (467 +/- 175 pg/ml) compared with that of patients experiencing severe rejection (8.4 +/- 3.7 pg/ml) (P < 0.002). These data support the concept of a cytokine (IFN-gamma)-mediated accelerated inflammatory response resulting in graft loss from necrotizing vasculitis--the clinical equivalent of an organ-specific Shwartzman reaction.
Background/Objectives:Laparoscopic living donor nephrectomy (LLDN) of the right kidney is currently considered as part of standard of care; however, dealing with the renal hilum when performing ligation/division of its renal vessels is... more
Background/Objectives:Laparoscopic living donor nephrectomy (LLDN) of the right kidney is currently considered as part of standard of care; however, dealing with the renal hilum when performing ligation/division of its renal vessels is still a main concern. Here, we describe a simple-to-perform technique, i.e., flipping the fully mobilized right kidney to the midline so that the renal artery becomes anteriorly, which offers better visualization and easier dissection of the renal vessels (achieving maximized lengths) when performing hand-assisted LLDN of the right kidney.Methods:Living donors who underwent hand-assisted LLDN of the right kidney, along with their respective renal transplant recipients, were included in this report. Donor characteristics included renal artery and vein lengths; recipient characteristics included creatinine at months 12 – 36. Graft vein and arterial anastomosis data were also reported.Results:Nineteen living donors and 19 recipients, with median donor and recipient ages being 39 (24 – 60) and 53 (3 – 81) years, respectively, were included. None of the 38 patients had intra- or postoperative complications. Donor renal vein was anastomosed to the right external iliac vein (n = 16), right common iliac vein (n = 2), and inferior vena cava (n = 1). Gonadal vein (n = 1) and deceased donor iliac vein (n = 2) were used to increase the right renal vein length in 3 cases. Four donor kidneys had 2 arteries reconstructed side by side. None of the recipients developed any vascular or urological complications.Conclusions:The laparoscopic technique described is safe and allows better visualization of the right hilum, mainly the renal artery, and helps in stapling the renal vein and renal artery.
The First World Consensus Conference on Pancreas Transplantation provided 49 jury deliberations regarding the impact of pancreas transplantation on the treatment of diabetic patients, and 110 experts’ recommendations for the practice of... more
The First World Consensus Conference on Pancreas Transplantation provided 49 jury deliberations regarding the impact of pancreas transplantation on the treatment of diabetic patients, and 110 experts’ recommendations for the practice of pancreas transplantation. The main message from this consensus conference is that both simultaneous pancreas‐kidney transplantation (SPK) and pancreas transplantation alone can improve long‐term patient survival, and all types of pancreas transplantation dramatically improve the quality of life of recipients. Pancreas transplantation may also improve the course of chronic complications of diabetes, depending on their severity. Therefore, the advantages of pancreas transplantation appear to clearly surpass potential disadvantages. Pancreas after kidney transplantation increases the risk of mortality only in the early period after transplantation, but is associated with improved life expectancy thereafter. Additionally, preemptive SPK, when compared to SPK performed in patients undergoing dialysis, appears to be associated with improved outcomes. Time on dialysis has negative prognostic implications in SPK recipients. Increased long‐term survival, improvement in the course of diabetic complications, and amelioration of quality of life justify preferential allocation of kidney grafts to SPK recipients. Audience discussions and live voting are available online at the following URL address: http://mediaeventi.unipi.it/category/1st‐world‐consensus‐conference‐of‐pancreas‐transplantation/246.
Transplantation of the urinary bladder has not been reported in humans. We transplanted a portion of the donor bladder with an en bloc kidney graft in a 12-month-old girl. The child had a congenital hypoplastic single kidney with an... more
Transplantation of the urinary bladder has not been reported in humans. We transplanted a portion of the donor bladder with an en bloc kidney graft in a 12-month-old girl. The child had a congenital hypoplastic single kidney with an ectopic ureteral opening into the vagina. Her native bladder was extremely small. Bilateral kidneys were transplanted en bloc with their ureters connected to a patch of the donor bladder, which encompassed the bilateral ureterovesical junctions (UVJs) (bladder patch technique). Approximately one-third of the donor bladder wall was used. The bladder patch reperfused well via blood supply from the ureters. Posttransplant cystoscopy with retrograde cystogram revealed a viable transplanted bladder with normal emptying of transplanted ureters. No reflux across the donor UVJs was seen in a voiding cystourethrogram. The child is doing well with normal renal function at 18-month follow-up.
Lipid dysmetabolism is one of the main features of diabetes mellitus and manifests by dyslipidemia as well as the ectopic accumulation of lipids in various tissues and organs, including the kidney. Research suggests that impaired... more
Lipid dysmetabolism is one of the main features of diabetes mellitus and manifests by dyslipidemia as well as the ectopic accumulation of lipids in various tissues and organs, including the kidney. Research suggests that impaired cholesterol metabolism, increased lipid uptake or synthesis, increased fatty acid oxidation, lipid droplet accumulation and an imbalance in biologically active sphingolipids (such as ceramide, ceramide-1-phosphate and sphingosine-1-phosphate) contribute to the development of diabetic kidney disease (DKD). Currently, the literature suggests that both quality and quantity of lipids are associated with DKD and contribute to increased reactive oxygen species production, oxidative stress, inflammation, or cell death. Therefore, control of renal lipid dysmetabolism is a very important therapeutic goal, which needs to be archived. This article will review some of the recent advances leading to a better understanding of the mechanisms of dyslipidemia and the role of particular lipids and sphingolipids in DKD.
Significance Statement A signaling molecule that plays a role in the innate immune system, stimulator of IFN genes (STING), is a crucial regulator of the cyclic GMP-AMP synthase (cGAS)-STING pathway. This signaling pathway regulates... more
Significance Statement A signaling molecule that plays a role in the innate immune system, stimulator of IFN genes (STING), is a crucial regulator of the cyclic GMP-AMP synthase (cGAS)-STING pathway. This signaling pathway regulates inflammation and energy homeostasis under conditions of obesity, kidney fibrosis, and AKI, but its exact role in the pathogenesis of glomerular diseases remains unclear. The authors found that activation of STING in wild-type mice is sufficient to cause albuminuria and podocyte loss, and that the cGAS-STING signaling pathway is upregulated in mice with experimental diabetic kidney disease and Alport syndrome. They also demonstrated that either genetic or pharmacologic STING inhibition confers protection from kidney disease progression. These findings suggest that this signaling pathway plays an important role in mediating glomerular dysfunction. Background The signaling molecule stimulator of IFN genes (STING) was identified as a crucial regulator of the DNA-sensing cyclic GMP-AMP synthase (cGAS)-STING pathway, and this signaling pathway regulates inflammation and energy homeostasis under conditions of obesity, kidney fibrosis, and AKI. However, the role of STING in causing CKD, including diabetic kidney disease (DKD) and Alport syndrome, is unknown. Methods To investigate whether STING activation contributes to the development and progression of glomerular diseases such as DKD and Alport syndrome, immortalized human and murine podocytes were differentiated for 14 days and treated with a STING-specific agonist. We used diabetic db/db mice, mice with experimental Alport syndrome, C57BL/6 mice, and STING knockout mice to assess the role of the STING signaling pathway in kidney failure. Results In vitro, murine and human podocytes express all of the components of the cGAS-STING pathway. In vivo, activation of STING renders C57BL/6 mice susceptible to albuminuria and podocyte loss. STING is activated at baseline in mice with experimental DKD and Alport syndrome. STING activation occurs in the glomerular but not the tubulointerstitial compartment in association with autophagic podocyte death in Alport syndrome mice and with apoptotic podocyte death in DKD mouse models. Genetic or pharmacologic inhibition of STING protects from progression of kidney disease in mice with DKD and Alport syndrome and increases lifespan in Alport syndrome mice. Conclusion The activation of the STING pathway acts as a mediator of disease progression in DKD and Alport syndrome. Targeting STING may offer a therapeutic option to treat glomerular diseases of metabolic and nonmetabolic origin or prevent their development, progression, or both.
Renal artery aneurysm is an infrequently seen disease. The most feared symptom is rupture, which is often rapidly fatal. Indications for intervention include size, intractable symptoms and pregnancy. Many cases are managed by endovascular... more
Renal artery aneurysm is an infrequently seen disease. The most feared symptom is rupture, which is often rapidly fatal. Indications for intervention include size, intractable symptoms and pregnancy. Many cases are managed by endovascular techniques; however, very complex cases often are referred to the urologist. We report our experience with the rarely used technique of renal artery aneurysms repair comprised of nephrectomy, extracorporeal vascular reconstruction with aneurysmectomy, and autotransplant.
Renal artery injury from blunt abdominal trauma is a rare condition that is typically managed nonoperatively in hemodynamically stable patients. Revascularization can be achieved by stenting or surgical reconstruction of the renal artery.... more
Renal artery injury from blunt abdominal trauma is a rare condition that is typically managed nonoperatively in hemodynamically stable patients. Revascularization can be achieved by stenting or surgical reconstruction of the renal artery. All attempts at revascularization should minimize warm ischemic time. Here, we discuss a patient postmotor vehicle accident who presented to Ryder Trauma Center with intra-abdominal bleeding. He underwent emergency exploratory laparotomy with splenectomy and abdominal packing. Postoperative CT scan revealed a contrast nonenhancing left kidney. The patient then returned to the operating room and underwent in situ renal artery reconstruction after >4 hours of warm ischemia. The patient survived a 2-month hospital course and was discharged home after prolonged in-hospital stay and intensive care treatment. Nuclear medicine scan showed scarring and atrophy of the reattached kidney with 16.3% of overall function attributed to the affected kidney. Thi...
We wanted to determine if parametric cause-specific hazard modeling, including log-linear generalizations of underlying parameters to incorporate covariate effects, would provide accurate representations, particularly with nonproportional... more
We wanted to determine if parametric cause-specific hazard modeling, including log-linear generalizations of underlying parameters to incorporate covariate effects, would provide accurate representations, particularly with nonproportional hazards. Nonparametric ...
Focal segmental glomerulosclerosis (FSGS) is a common glomerular disorder that manifests clinically with the nephrotic syndrome and has a propensity to recur following kidney transplantation. The pathophysiology and therapies available to... more
Focal segmental glomerulosclerosis (FSGS) is a common glomerular disorder that manifests clinically with the nephrotic syndrome and has a propensity to recur following kidney transplantation. The pathophysiology and therapies available to treat FSGS currently remain elusive. Since the podocyte appears to be the target of apparent circulating factor(s) that lead to recurrence of proteinuria following kidney transplantation, this article is focused on the podocyte. In the context of kidney transplantation, the performance of pre- and post-reperfusion biopsies, and the establishment of in vitro podocyte liquid biopsies/assays allow for the development of clinically relevant studies of podocyte biology. This has given insight into new pathways, involving novel targets in innate and adaptive immunity, such as SMPDL3b, cGAS-STING, and B7-1. Elegant experimental studies suggest that the successful clinical use of rituximab and abatacept, two immunomodulating agents, in our case series, may...
HPV: human papillomavirus INTRODUCTION Patients with acquired immune deficiency syndrome or immunosuppression due to solid organ transplantation are at increased risk of treatmentresistant cutaneous warts, also known as recalcitrant... more
HPV: human papillomavirus INTRODUCTION Patients with acquired immune deficiency syndrome or immunosuppression due to solid organ transplantation are at increased risk of treatmentresistant cutaneous warts, also known as recalcitrant warts. There are numerous treatments for cutaneous warts, with varying efficacy and recurrence rates; overall, recurrence is common. We present the case of a 66-year-old woman with recalcitrant warts successfully treated with systemic administration of the 9-valent human papillomavirus (HPV) vaccine (Gardasil 9, Merck & Co Inc) prior to renal transplant.
BackgroundThe Coronavirus disease 2019(COVID‐19) pandemic has negatively impacted worldwide organ transplantation. However, there is limited information on recipients transplanted after SARS‐CoV‐2 infection. A full understanding of this... more
BackgroundThe Coronavirus disease 2019(COVID‐19) pandemic has negatively impacted worldwide organ transplantation. However, there is limited information on recipients transplanted after SARS‐CoV‐2 infection. A full understanding of this scenario is required, as transplantation is a life‐saving procedure and COVID‐19 remains an ongoing threat.MethodsAbdominal organ transplant recipients diagnosed with COVID‐19 prior to transplantation were identified by chart review and clinical data were collected. The primary outcome was the transplant outcome including graft loss, rejection and death, and reactivation of infection post‐transplant.ResultsWe identified 14 patients who received abdominal organ transplants after symptomatic PCR confirmed SARS‐CoV‐2 infection; four patients had a positive PCR at the time of admission for transplantation. The median time of follow‐up was 79 (22‐190) days. One recipient with negative PCR before transplant tested positive 9 days after transplant. One of 1...
Pancreas transplant achieves consistent long‐term euglycemia in type 1 diabetes. Allograft thrombosis (AT) causes the majority of early graft failure. We compared outcomes of four anticoagulation regimens administered to 95 simultaneous... more
Pancreas transplant achieves consistent long‐term euglycemia in type 1 diabetes. Allograft thrombosis (AT) causes the majority of early graft failure. We compared outcomes of four anticoagulation regimens administered to 95 simultaneous kidney‐pancreas or isolated pancreas transplanted between 1/1/2015 and 11/20/2018. Early postoperative anticoagulation regimens included the following: none, subcutaneous heparin/aspirin, with or without dextran, and heparin infusion. The regimens were empirically selected based on each surgeon's assessment of hemostasis of the operative field and personal preference. A sonographic‐based global scoring system of AT is presented. The 47‐month recipients and graft survival were 95% and 86%, respectively. Recipients with or without AT had similar survival. Five and four grafts were lost due to death and AT, respectively. Outcomes of prophylaxis regimens correlated with intensity of anticoagulation. Compared with no anticoagulation, an increase in he...
Background African Americans with lupus who receive kidney transplants have high prevalence of predictors of allograft failure, which can explain their poor outcomes. Methods Of 1223 African Americans and 1029 Caucasian Americans with... more
Background African Americans with lupus who receive kidney transplants have high prevalence of predictors of allograft failure, which can explain their poor outcomes. Methods Of 1223 African Americans and 1029 Caucasian Americans with lupus who received kidney transplants from deceased donors between 1987 and 2006 with complete records in the UNOS program, 741 pairs were matched in 16 predictors employing a predicted probability of group membership. The primary outcome was allograft failure. Main secondary outcomes were rejection, allograft failure due to rejection, and mortality. Results Matched pairs were predominantly women (82%) with a mean age of 39 years. Twenty-four percent of recipients received kidneys from expanded criteria donors. African Americans and Caucasian Americans matched well ( p ≥ 0.05): donor age, gender and race; recipient age, gender, education and insurance; dialysis prior to transplant, kidneys from expanded criteria donors, cold ischemia time, history of p...
Advances in technical aspects of pancreas transplantation and improvements in immunosuppression over the last decade have led to significant improvements in pancreas transplant outcomes in the short-term. Simultaneous kidney pancreas... more
Advances in technical aspects of pancreas transplantation and improvements in immunosuppression over the last decade have led to significant improvements in pancreas transplant outcomes in the short-term. Simultaneous kidney pancreas transplantation remains an attractive option for patients with type 1 diabetes (T1DM) and late chronic kidney disease (CKD), with 1-year pancreas graft survival rates of 86% in 2004. For the individual patient with T1DM and CKD, the various transplant options must be considered carefully, with attention to the timing of surgery relative to the need for dialysis, the challenge in managing diabetes with noninvasive medical therapy, and the assumption of risks attendant to each surgical option. This review summarizes the current status of simultaneous pancreas kidney transplantation and compares and contrasts outcomes with other potential treatment options.
Background Primary FSGS manifests with nephrotic syndrome and may recur following KT. Failure to respond to conventional therapy after recurrence results in poor outcomes. Evaluation of podocyte B7-1 expression and treatment with... more
Background Primary FSGS manifests with nephrotic syndrome and may recur following KT. Failure to respond to conventional therapy after recurrence results in poor outcomes. Evaluation of podocyte B7-1 expression and treatment with abatacept (a B7-1 antagonist) has shown promise but remains controversial. Methods From 2012 to 2020, twelve patients developed post-KT FSGS with nephrotic range proteinuria, failed conventional therapy, and were treated with abatacept. Nine/twelve (< 21 years old) experienced recurrent FSGS; three adults developed de novo FSGS, occurring from immediately, up to 8 years after KT. KT biopsies were stained for B7-1. Results Nine KTRs (75%) responded to abatacept. Seven of nine KTRs were B7-1 positive and responded with improvement/resolution of proteinuria. Two patients with rFSGS without biopsies resolved proteinuria after abatacept. Pre-treatment UPCR was 27.0 ± 20.4 (median 13, range 8–56); follow-up UPCR was 0.8 ± 1.3 (median 0.2, range 0.07–3.9, p &lt...

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