Obesity and bariatric surgery in kidney transplantation: A clinical review.

Obesity is increasing worldwide, and this has major implications in the setting of kidney transplantation. Patients with obesity may have limited access to transplantation and increased posttransplant morbidity and mortality. Most transplant centers incorporate interventions aiming to target obesity in kidney transplant candidates, including dietary education and lifestyle modifications. For those failing nutritional restriction and medical therapy, the use of bariatric surgery may increase the transplant candidacy of patients with obesity and end-stage renal disease (ESRD) and may potentially improve the immediate and late outcomes. Bariatric surgery in ESRD patients is associated with weight loss ranging from 29.8% to 72.8% excess weight loss, with reported mortality and morbidity rates of 2% and 7%, respectively. The most commonly performed bariatric surgical procedures in patients with ESRD and in transplant patients are laparoscopic sleeve gastrectomy (LSG) and laparoscopic Roux-en-Y gastric bypass. However, the correct timing of bariatric surgery and the ideal type of surgery have yet to be determined, although pretransplant LSG seems to be associated with an acceptable risk-benefit profile. We review the impact of obesity on kidney transplant candidates and recipients and in potential living kidney donors, exploring the potential impact of bariatric surgery in addressing obesity in these populations, thereby potentially improving posttransplant outcomes.

Abdominal wall complications after kidney transplantation: A clinical review.

INTRODUCTION: Abdominal wall complications are common after kidney transplantation, and although they have a minor impact on patient and graft survival, they increase the patient's morbidity and may have an impact on quality of life. Abdominal wall complications have an overall incidence of 7.7-21%. METHODS: This review will explore the natural history of abdominal wall complications in the kidney transplant setting, with a special focus on wound dehiscence and incisional herni, with a particular emphasis on risk factors, clinical characteristics, and treatment. RESULTS: Many patient-related risk factors have been suggested, including older age, obesity, and smoking, but kidney transplant recipients have an additional risk related to the use of immunosuppression. Wound dehiscence usually does not require surgical intervention. However, for deep dehiscence involving the fascial layer with concomitant infection, surgical treatment and/or negative pressure wound therapy may be required. CONCLUSIONS: Incisional hernia (IH) may affect 1.1-18% of kidney transplant recipients. Most patients require surgical treatment, either open or laparoscopic. Mesh repair is considered the gold standard for the treatment of IH, since it is associated with a low rate of postoperative complications and an acceptable rate of recurrence. Biologic mesh could be an attractive alternative in patients with graft exposition or infection.

Colorectal Cancer after Kidney Transplantation: A Screening Colonoscopy Case-Control Study.

The incidence of colorectal cancer in kidney transplant recipients has been previously reported with conflicting results. In this study, we investigated if the incidence of colorectal advanced neoplasms in kidney transplant recipients, evaluated with screening colonoscopy, was higher than in healthy individuals. One-hundred sixty kidney transplant recipients undergoing screening colonoscopy were compared with 594 age- and sex-matched healthy individuals. Advanced colorectal neoplasia was found in 22 patients (13.7%), including four patients (2.5%) with colorectal cancer. Compared with the healthy population, kidney transplant recipients did not have an increased risk of developing a colorectal cancer (OR 0.69; 95% CI 0.236-2.063, p = 0.688) although it developed at a younger age. In contrast, kidney transplant recipients had a higher risk of developing an advanced adenoma compared with the control group (OR 1.65; 95% CI 0.930-2.981, p = 0.04). In conclusion, kidney transplant recipients did not have an increased incidence of colorectal cancer compared with healthy population. However, transplant patients displayed a higher incidence of colorectal adenomas, suggesting that screening colonoscopy in kidney transplant recipients should be expanded to include even younger recipients (<50 years old).

Post-transplant colitis after kidney transplantation: clinical, endoscopic and histological features.

Chronic immunosuppression may increase the risk of post-transplant infection and medication-related injury and may also be responsible for the increased risk of gastrointestinal complications in kidney transplant recipients. Differentiating the various forms of post-transplant colitis is challenging, since most have similar clinical and histological features. This study evaluated the incidence of post-transplant gastrointestinal complications during screening colonoscopy. Kidney transplant recipients undergoing a colonoscopy for any reasons in the period 2014-2018 were included. Among the 134 patients completing the colonoscopy, 74 patients (56%) had an abnormal finding: an adenoma was found in 25 patients (18.6%), while 19 patients (14.1%) had colitis. Mycophenolic acid/related colitis was the most common colitis (6%), while 7 patients (5.2%) developed a de novo inflammatory bowel disease. Patients with post-transplant colitis were younger and with shorter time from transplant compared to patients without colitis. In conclusions, immunosuppression may predispose kidney transplant recipients to an increased risk of post-transplant colitis. Diagnostic colonoscopy should be encouraged in all transplant patients with refractory diarrhea and gastrointestinal symptoms to allow a prompt diagnosis and a timely treatment, finally improving the quality of life and long-term outcomes of affected patients.

Heme Oxygenase-1 and Carbon Monoxide Regulate Growth and Progression in Glioblastoma Cells.

In human glioma tumours, heme oxygenase-1 (HO-1) is overexpressed when compared with normal brain tissues and during oligodendroglioma progression. However, the molecular mechanisms mediated by HO-1 to promote glioblastoma remain unknown. We therefore aimed at investigating the effect of HO-1 expression and its selective enzymatic inhibition in two different cell lines (i.e. A172 and U87-MG). HO-1 was induced by hemin treatment (10 µM), and VP13/47 (100 µM) was used as a specific non-competitive inhibitor of HO-1 activity. Cell proliferation was measured by cell index measurement (xCelligence technology) and clonogenic assay, whereas cell migration was assessed by wound healing assay. Carbon monoxide-releasing molecules (CORMs) (i.e. CORM-3 and CORM-A1) were also used in a separate set of experiments to confirm the effect of HO-1 by-product in glioblastoma progression further. Our results were further validated using GSE4412 microarray dataset analysis and comparing biopsies overexpressing HO-1 with the rest of the cases. Our results showed that hemin was able to induce both HO-1 gene and protein expression in a cell-dependent manner being A172 more responsive to pharmacological upregulation of HO-1. Hemin, but not CORMs treatment, resulted in a significant increase of cell proliferation following 24 h of treatment as measured by increased cell index and colony formation capacity and such effect was abolished by VP13/47. Interestingly, both hemin and CORMs showed a significant effect on the wound healing assay also exhibiting cell specificity. Finally, our dataset analysis showed a positive correlation of HO-1 gene expression with ITGBI and ITGBII which are membrane receptors involved in cell adhesion, embryogenesis, tissue repair, immune response and metastatic diffusion of tumour cells. In conclusion, our data suggest that HO-1 and its by-product CO exhibit a cell-specific effect on various aspects of disease progression and are associated with a complex series of molecular mechanisms driving cell proliferation, survival and metastasis.

De Novo Cancer Incidence and Prognosis After Kidney Transplantation: A Single Center Analysis.

BACKGROUND: Malignancy is an important cause of mortality in renal transplants recipients. The aim of this study was to evaluate the incidence, prognosis, and survival of patients developing a de novo post-transplant cancer. METHODS: Using a retrospective cohort design, we evaluated the incidence of de novo cancers among kidney transplants patients in our hospital from January 2000 to December 2012. We also evaluated the patient survival after tumor diagnosis. RESULTS: We included 535 kidney transplants recipients with a mean follow-up of 7.8 years; among them, 39 (7.2%) developed malignancies. Median time from transplant to cancer diagnosis was 3 years, with a median age at diagnosis of 60 years. Male patients were significantly older at time of cancer diagnosis (68.5 years) compared with women (38 years, P < .05), and cancer diagnosis occurred significantly earlier in men (3.5 years since transplantation) than in women (8.5 years, P < .05). Among 39 patients affected by a de novo post-transplant cancer, 18 patients (46.2%) died, with an average age at death of 58.5 years. The average time from cancer diagnosis to death was 1.5 years. Among the group of patients who did not develop a post-transplant cancer, 83 patients (16.7%) died, with a median age at time of death of 54.5 years (P < .05). CONCLUSIONS: Kidney transplant recipients are at higher risk of developing a post-transplant cancer. Prognosis after cancer diagnosis is poor, probably as a consequence of a more aggressive behavior of cancer in transplant recipients. Intensive screening protocols could allow for an earlier diagnosis thereby improving the long-term outcome of these patients.

Impact of Incidental Findings During the Evaluation of Live Kidney Donors on Post-Transplant Outcomes: A Single Center Analysis.

BACKGROUND: A careful assessment of a living donor is mandatory to minimize the short- and long-term risk related to kidney donation. In this study, we evaluated the incidence of incidental findings (IFs) in a large population of potential living kidney donors. Moreover, this study evaluated if the presence of IFs could influence the chance of living kidney donation and post-transplant outcomes. METHODS: One hundred and sixty consecutive potential prospective living kidney transplant donors, who underwent a multidetector computed tomography angiography (MDCTA), were included in the study. An IF was defined as an incidentally discovered mass or lesion, detected by computed tomography angiography during the imaging evaluation of potential living donors. Clinical outcomes of living donors with IF were compared with those without IF. RESULTS: In 10 patients (6.2%) an incidental finding was detected at MDCTA assessment. Among the 10 patients presenting with an IF, 7 patients (4.3%) were excluded from the living donation: 2 patients with an adrenal lesion, 3 patients with cancer, and 2 patients with a large (>8 cm) renal cyst. Graft and patient survival of kidney transplant recipients of donors with IFs were not significantly different to those receiving a kidney from living donors without IFs. CONCLUSIONS: Incidental findings are frequently discovered during living kidney donor evaluation. Whereas most are asymptomatic or not clinically relevant, predonation screening could identify potentially life-threatening diseases at an earlier stage, allowing for a more radical treatment.

Thyroid disease and cancer in kidney transplantation: a single-center analysis.

BACKGROUND: Thyroid diseases are frequent in patients with end-stage renal disease, but data on renal transplant recipients are conflicting. This study evaluated the incidence of thyroid disease and cancer in a population of kidney transplant recipients performed in a single center. METHODS: Seven hundred sixty patients receiving a kidney transplantation between January 2000 and October 2017 were followed with thyroid ultrasonography to determine nodules together with thyroid hormone levels. Ultrasound-guided fine-needle aspiration citology (FNAc) was performed to the nodules > 10 mm . RESULTS: Two hundred four patients (26.8%) patients demonstrated functional or morphologic changes in the thyroid gland compared with pre-transplant period. Among the 204 patients with newly diagnosed thyroid disease, 165 patients had single or multiple nodular lesions less than 1 cm in diameter, and were followed yearly. Nodule size progression was observed in 23 patients (13.9%), and they underwent a FNAc. A total of sixty-two patients (30.3%) underwent FNAc. The biopsy samples were cytologically interpreted as benign in 20 patients (32.2%), suspicious in 40 patients (64.5%), or at high risk of cancer in 2 patients (3.2%). Forty-two patients underwent total thyroidectomy. At histological examination, 18 patients had a thyroid cancer (papillary cancer in 17 patients, follicular cancer in one). Thyroid cancer was more frequent in male patients with a mean time from transplant to diagnosis of 5.6 years. At a mean follow-up was 8 ± 1.2 years, all patients are alive with a normal functioning graft. CONCLUSIONS: Thyroid diseases are common in transplant recipients. Thyroid disease may evolve after transplantation, probably as a consequence of immunosuppression. A complete evaluation of thyroid disease is mandatory in kidney transplant recipients because early diagnosis and appropriate treatment of thyroid disease and cancer may significantly decrease the morbidity and mortality in these patients.

Mesenteric lymph nodes as alternative site for pancreatic islet transplantation in a diabetic rat model.

BACKGROUND: Islet transplantation has progressively become a safe alternative to pancreas transplantation for the treatment of type 1 diabetes. However, the long-term results of islet transplantation could be significantly increased by improving the quality of the islet isolation technique even exploring alternative islet transplantation sites to reduce the number of islets required to mitigate hyperglycemia. The goal of the study was to test the lymph node as a suitable anatomical location for islet engraftment in a rodent model. METHODS: Forty Lewis rats, 6-8 weeks old, body weight 250-300 g, have been used as islet donors and recipients in syngeneic islet transplantation experiments. Ten rats were rendered diabetic by one injection of 65 mg/Kg of streptozotocin. After pancreas retrieval from non diabetic donors, islet were isolated and transplanted in the mesenteric lymph nodes of 7 diabetic rats. Rats were followed for 30 days after islet transplantation. RESULTS: A total of 7 islet transplantations in mesenteric lymph nodes have been performed. Two rats died 24 and 36 h after transplantation due to complications. No transplanted rat acquired normal glucose blood levels and insulin independence after the transplantation. However, the mean blood levels of glycemia were significantly lower in transplanted rats compared with diabetic rats (470.4 mg/dl vs 605 mg/dl, p 0.04). Interestingly, transplanted rats have a significant weight increase after transplantation compared to diabetic rats (mean value 295 g in transplanted rats vs 245 g in diabetic rats, p < 0.05), with an overall improvement of social activities and health. Immunohistochemical analysis of the 5 mesenteric lymph nodes of transplanted rats demonstrated the presence of living islets in one lymph node. CONCLUSIONS: Although islet engraftment in lymph nodes is possible, islet transplantation in lymph nodes in rats resulted in few improvements of glucose parameters.

Change in kidney volume after kidney transplantation in patients with autosomal polycystic kidney disease.

BACKGROUND: The indication to bilateral nephrectomy in patients with autosomal dominant polycystic kidney scheduled for kidney transplantation is controversial. Indeed, the progressive enlargement of cysts may increase the risk of complications and the need for nephrectomy. However, very few studies investigated the change in kidney volume after kidney transplantation. MATERIAL AND METHODS: In this prospective cohort study, the change in native kidney volume in polycystic patients was evaluated with magnetic resonance imaging. Forty patients were included in the study. Kidney diameters and total kidney volume were evaluated with magnetic resonance imaging in patients who underwent simultaneous nephrectomy and kidney transplantation and in patients with kidney transplant alone, before transplantation and 1 year after transplantation. RESULTS: There was a significant reduction of kidney volume after transplantation, with a mean degree of kidney diameters reduction varying from 12.24% to 14.43%. Mean total kidney volume of the 55 kidney considered in the analysis significantly reduced from 1617.94 ± 833.42 ml to 1381.42 ± 1005.73 ml (P<0.05), with a mean rate of 16.44% of volume decrease. More than 80% of patients had a volume reduction in both groups. CONCLUSIONS: Polycystic kidneys volume significantly reduces after kidney transplantation, and this would reduce the need for prophylactic bilateral nephrectomy in asymptomatic patients.

Rare cause of odynophagia: Giant esophageal ulcer.

Gastrointestinal complications are a frequent cause of morbidity after transplantation and may affect up to 40% of kidney transplant recipients. Here we report a rare case of idiopathic giant esophageal ulcer in a kidney transplant recipient. A 37-year-old female presented with a one-week history of odynophagia and weight loss. Upon admission, the patient presented cold sores, and a quantitative cytomegalovirus polymerase chain reaction was positive (10(5) copies/mL). An upper endoscopy demonstrated the presence of a giant ulcer. Serological test and tissue biopsies were unable to demonstrate an infectious origin of the ulcer. Immunosuppression was reduced and everolimus was introduced. An empirical i.v. therapy with acyclovir was started, resulting in a dramatic improvement in symptoms and complete healing of the ulcer. Only two cases of idiopathic giant esophageal ulcer in kidney transplant recipients have been reported in the literature; in both cases, steroid therapy was successful without recurrence of symptoms or endoscopic findings. However, this report suggests that correction of immune imbalance is mandatory to treat such a rare complication.

Exploring new frontiers: sirolimus as a pharmacokinetic modulator in advanced cancer patients.

The mTOR pathway mediates many biologic functions such as transcriptional and translational control, and is a target for anticancer drug development. mTOR inhibitors, such as sirolimus (SRL), display immunosuppressive and antiproliferative properties, and the use of SRL in kidney transplant recipients reduces the risk of post-transplant cancer. However, its use in advanced cancer patients has not been fully evaluated. The authors review the study by Cohen et al., evaluating the dose for oral, weekly SRL alone or in combination with grapefruit juice or ketoconazole to achieve the desired whole-blood concentration with antitumoral activity. This study demonstrates that SRL can be feasibly administered orally once weekly and displays a similar pharmacokinetic profile compared with other mTOR inhibitors. This study encouraged the use of SRL in advanced cancer patients and can stimulate clinical trials with a larger number of patients, evaluating the role of SRL as a new targeted therapy in cancer patients.

Sirolimus in solid organ transplantation: current therapies and new frontiers.

Sirolimus (SRL) is a mammalian target of rapamycin inhibitor, which provides an immunosuppressive effect by inhibiting cell cycle progression. The encouraging results of combined SRL-cyclosporine therapy paved the way to further immunosuppressant combinations. Although SRL is relatively non-nephrotoxic when administered as monotherapy, it pharmacodynamically enhances the toxicity of calcineurin inhibitors. Other side effects may include hyperlipidemia and myelosuppression and less commonly wound healing impairment, proteinuria, edema and pneumonitis. Surprisingly, SRL also showed encouraging properties as an antiatherogenic and antineoplastic, opening a large spectrum of new potential applications. Whether SRL can be used safely over the long term with low doses of calcineurin inhibitors requires further study. The use of SRL as a corticosteroid-sparing agent also remains to be proven in controlled trials.

Chylous ascites following laparoscopic living donor nephrectomy. Case report.

Kidney transplantation is a therapeutic option of choice for patients with end-stage disease. Laparoscopic living donor nephrectomy (LLDN) is a less invasive alternative to the open procedure to increase the number of renal donors. However, several studies have reported that this technique requires a long learning curve, and that the complication rate varies from 6.4% to 16.5%. Among these, chylous ascites (CA) is a severe and rare complications of LLDN. The treatment option for this condition is primarily conservative. Surgery is considered after failure of conservative treatment and its role, however, remains controversial. We report a case of CA as a complication of laparoscopic donor nephrectomy. A 44 year old woman underwent LLDN of the left kidney. There were no intraoperative or immediate postoperative complications and the patient was discharged home on postoperative day 3. Two weeks after discharge, the patient returned for a routine follow-up visit and presented with abdominal distension, discomfort, and dyspnea. A CT scan of the abdomen with oral and intravenous contrast revealed significant ascites in all four quadrants of abdomen and pelvis. An ultrasound guided paracentesis was performed, and 7 L of chyle was aspirated Conservative management with medium chain triglyceride and spironolactone was immediately initiated; the symptoms improved after paracentesis, and the CA completely resolved after 3 days of therapy. However, to prevent recurrence, the patient consumed a low-fat medium chain triglyceride diet for 6 months. CA needs to be considered as a potential severe and rare complication of LLDN, and conservative management should be proposed to all patients, reserving the surgical treatment to treatment failure.

Anaesthesiological implications of Kimura's disease: a case report.

INTRODUCTION: Kimura's disease is a chronic inflammatory condition belonging to the angio-lymphatic proliferative group of disorders, usually affecting young men of Asian race, but is rare in Western countries. It is a benign but locally injurious disease, of unknown aetiology, whose classical clinical features are a tumour-like swelling, usually in the head and neck, with or without satellite lymphadenopathy, often accompanied by eosinophilia and elevated serum IgE. CASE PRESENTATION: We report the case of a 33-year-old Caucasian woman with an atypical localization of Kimura's disease, discussing the anaesthesiological implications and reviewing the current literature on Kimura's disease. CONCLUSIONS: The diagnosis of Kimura's disease can be difficult and misleading, and anaesthesiological precautions could be ignored. Patients with this disease are often evaluated for other disorders: unnecessary diagnostic tests and investigations, or even surgery, may be avoided by just being aware of Kimura's disease.

Anaesthesiologic protocol for kidney transplantation in two patients with Fabry Disease: a case series.

Fabry's Disease is a rare genetic syndrome, with a classic X-linked alpha -galactosidase A deficiency phenotype, responsible for glico-sphyngolypids metabolism impairment with clinical effects in several organs and functions. We describe the anaesthesiologic implications of two patients with Fabry disease who underwent a kidney transplantation from a deceased donor. We recommend careful preoperative evaluation, including cardiac sonography study and spirometry for Fabry disease patients, and according to our experience, we recommend advanced haemodynamic monitoring during surgery. Careful airway examination should be further performed, with particular attention to patient ventilability prediction and available alternative strategies for airway management in case of difficulties. A nephroprotective strategy and a particular care to the associated end-stage organ disease may significantly improve the long-term outcome of patients with Fabry Disease.

Klebsiella pneumoniae pulmonary infection with thyroid abscess: report of a case.

Thyroid abscess is a rare clinical entity, usually associated with a pyriform sinus fistula. A prompt diagnosis is important because it may progress rapidly into a life-threatening condition. We report a very unusual case of thyroid abscess associated with a lung infection, both caused by Klebsiella pneumoniae. The patient was treated successfully with a culture-appropriate antibiotic and an uneventful thyroid lobectomy. A delay in diagnosis of morbidities associated with a thyroid abscess may result in rapid exacerbation of this condition; therefore, prompt and appropriate treatment is mandatory for a successful outcome.

Cytomegalovirus and Clostridium difficile ischemic colitis in a renal transplant recipient: a lethal complication of anti-rejection therapy?

Intestinal ischemia is reported to be the most common gastrointestinal complication of renal transplantation and a potential cause of morbidity and mortality. The recent use of more potent immunosuppressive drug regimens has reduced the incidence of acute rejection, increasing the incidence of potentially fatal infectious complications, such as clinically important cytomegalovirus (CMV) infection. A 42-year-old kidney transplant recipient experienced on postoperative day 10 a dehiscence of the ureterovesical anastomosis, associated with a 7-cm longitudinal tear graft on the lower pole of the kidney and an ureteral ischemia. A graft biopsy demonstrated a mild acute rejection for which the patient received an unsuccessful administration of steroids, with progression of the rejection, so that 1 mg/kg/day antithymocyte globulin was administered. Two days later the patient presented with fever (39.5 degrees C), diffuse abdominal pain with tenderness and bloody diarrhea, and diagnosis of CMV colitis was achieved; rectal samples were taken for histologic examination, and Clostridium difficile toxin was isolated. A subtotal colectomy with Hartmann's procedure was performed, but the patient died 13 days later of a multiple organ failure. The risk of lethal CMV colitis is increased in patients being treated with anti-rejection therapy for severe acute rejection; the occurrence of simultaneous infection, such as pseudomembranous colitis, usually characterized by a favorable prognosis, increases the mortality rate in these patients.