Human cytomegalovirus-related gastrointestinal disease after kidney transplantation: A systematic review.

BACKGROUND: Human-cytomegalovirus (hCMV) infection involving the gastrointestinal tract represents a leading cause of morbidity and mortality among kidney transplant (KT) recipients (KTRs). Signs and symptoms of the disease are extremely variable. Prompt anti-viral therapy administration and immunosuppression modification are key factors for optimizing management. However, complex work-up strategies are generally required to confirm the preliminary diagnosis. Unfortunately, solid evidence and guidelines on this specific topic are not available. We consequently aimed to summarize current knowledge on post-KT hCMV-related gastrointestinal disease (hCMV-GID). METHODS: We conducted a systematic review (PROSPERO ID: CRD42023399363) about hCMV-GID in KTRs. RESULTS: Our systematic review includes 52 case-reports and ten case-series, published between 1985 and 2022, collectively reporting 311 cases. The most frequently reported signs and symptoms of hCMV-GID were abdominal pain, diarrhea, epigastric pain, vomiting, fever, and GI bleeding. Esophagogastroduodenoscopy and colonoscopy were the primary diagnostic techniques. In most cases, the preliminary diagnosis was confirmed by histology. Information on anti-viral prophylaxis were extremely limited as much as data on induction or maintenance immunosuppression. Treatment included ganciclovir and/or valganciclovir administration. Immunosuppression modification mainly consisted of mycophenolate mofetil or calcineurin inhibitor minimization and withdrawal. In total, 21 deaths were recorded. Renal allograft-related outcomes were described for 26 patients only. Specifically, reported events were acute kidney injury (n = 17), transplant failure (n = 5), allograft rejection (n = 4), and irreversible allograft dysfunction (n = 3). CONCLUSIONS: The development of local and national registries is strongly recommended to improve our understanding of hCMV-GID. Future clinical guidelines should consider the implementation of dedicated diagnostic and treatment strategies.

Are there any relations among transplant centre volume, surgical technique and anatomy for donor graft selection? Ten-year multicentric Italian experience on mini-invasive living donor nephrectomy.

BACKGROUND: Selection of the right or left living donor kidney for transplantation is influenced by many variables. In the present multi centric study including 21 Italian transplant centres, we evaluated whether centre volume or surgical technique may influence the selection process. METHODS: Intra- and perioperative donor data, donor kidney function, and recipient and graft survival were collected among 693 mini-invasive living donor nephrectomies performed from 2002 to 2014. Centre volume (LOW, 1-50 cases; HIGH, >50 cases) and surgical technique (FULL-LAP, full laparoscopic and robotic; HA-LAP, hand-assisted laparoscopy; MINI-OPEN, mini-lumbotomy) were correlated with selection of right or left donor kidney and with donor and recipient outcome. RESULTS: HIGH-volume centres retrieved a higher rate of donor right kidneys (29.3% versus 17.6%, P < 0.01) with single artery (83.1% versus 76.4%, P < 0.05) compared with LOW-volume centres. Surgical technique correlated significantly with rate of donor right kidney and presence of multiple arteries: MINI-OPEN (53% and 13%) versus HA-LAP (29% and 22%) versus FULL-LAP (11% and 23%), P < 0.001 and P < 0.05, respectively. All donors had an uneventful outcome; donor bleeding was more frequent in LOW-volume centres (4% versus 0.9%, P < 0.05). CONCLUSIONS: Centre volume and surgical technique influenced donor kidney side selection. Donor nephrectomy in LOW-volume centres was associated with higher risk of donor bleeding.

Changes of liver enzymes and bilirubin during ischemic stroke: mechanisms and possible significance.

BACKGROUND: Small changes of bilirubin and liver enzymes are often detected during the acute phase of stroke, but their origin and significance are still poorly understood. METHODS: On days 0, 3, 7, and 14 after admission, 180 patients with ischemic stroke underwent serial determinations of bilirubin, GOT, GPT, γGT, alkaline phosphatase, C-reactive protein (CRP) and complete blood count. On days 0 and 7 common bile duct diameter was measured by ultrasound, and on day 3 cerebral infarct volume (IV) was calculated from CT scan slices. RESULTS: During the first week GOT, GPT, γGT (P < 0.001) and CRP (P = 0.03) increased with subsequent plateau, while significant decrements (P < 0.001) concerned unconjugated bilirubin, erythrocytes and haemoglobin. Alkaline phosphatase, direct bilirubin and common bile duct diameter remained stable. IV correlated with CRP, leukocytes, GOT, γGT (r > 0.3, P < 0.001 for all) and direct bilirubin (r = 0.23, P = 0.008). In multivariate analysis only CRP and GOT remained independently associated with IV (P < =0.001). The correlation of IV with GOT increased progressively from admission to day 14. GOT independently correlated with GPT which, in turn, correlated with γGT. γGT was also highly correlated with leukocytes. Unconjugated bilirubin correlated with haemoglobin, which was inversely correlated with CRP. CONCLUSIONS: The changes of bilirubin and liver enzymes during ischemic stroke reflect two phenomena, which are both related to IV: 1) inflammation, with consequent increment of CRP, leukocytes and γGT, and decrease of haemoglobin and unconjugated bilirubin and 2) an unknown signal, independent from inflammation, leading to increasing GOT and GPT levels.

Tacrolimus-Associated Terminal Ileitis After Kidney Transplantation, Mimicking Crohn Disease: A Case Report.

The onset of gastroduodenal ulcers is a frequent complication after transplantation, whereas cases of intestinal ulcers are sporadic and poorly described in the literature. A patient on immunosuppressive therapy with tacrolimus and mycophenolate mofetil after kidney transplant for immunoglobulin A-related glomerulonephritis developed symptoms compatible with Crohn disease 7 months after the transplant. The patient was hospitalized for abdominal pain, diarrhea, fever, and weight loss. Imaging and a colonoscopy showed signs of idiopathic inflammatory bowel disease (IBD) affecting the terminal ileum. Behcet's disease, post-transplant lymphoma, cytomegalovirus, Epstein-Barr virus, or mycobacteria infection were excluded. Mycophenolate mofetil was suspended, and steroid therapy was increased without clinical improvement. Eleven units of blood were required for severe anemia. A further colonoscopy revealed ulcerations involving the cecal fundus, ileocecal valve, and distal ileum with bowel stenosis and suspected ischemia. The patient, therefore, underwent an emergency laparoscopic ileocolic resection. The histologic examination did not reveal clear signs of IBD, ischemia, or viral infection of the ileum. The findings seemed indicative of iatrogenic damage from immunosuppressive therapy. The postoperative course was regular, and after 12 months, the patient was asymptomatic, on low-dose tacrolimus and prednisone therapy. During immunosuppressive therapy, the onset of isolated ileal ulcers, which can mimic IBD, may be a sporadic complication.

Primary versus Salvage Liver Transplantation after Curative-Intent Resection or Radiofrequency Ablation for Hepatocellular Carcinoma: Long-Term Oncological Outcomes.

Liver transplantation for hepatocellular carcinoma (HCC) may be performed ab initio, primary liver transplantation (PLT), or for HCC recurrence after previous treatments such as liver resection (LR) or radiofrequency ablation (RFA), salvage liver transplantation (SLT). The aim of this study was to evaluate the oncological outcomes of SLT vs. PLT. For this, a retrospective study was carried out on patients undergoing liver transplantation for HCC. The outcomes of PLT were compared with those of SLT. The primary outcome was disease-free survival (DFS). The secondary outcomes included overall survival (OS), cancer-specific survival (CSS), and major postoperative complications. A sub-analysis of SLT-LR and SLT-RFA was also performed. In total, 141 patients were included: 96 underwent PLT and 45 SLT. Among the SLT group, 25 patients had undergone previous LR while 20 had had RFA. There were no differences in the major postoperative complications. Unadjusted DFS was significantly longer in the PLT group (p = 0.02), as were OS (p = 0.025) and CSS (p = 0.001). There was no difference in DFS between PLT and SLT-LR groups, while a significant difference was found between the PLT and SLT-RFA groups (p = 0.035). Nonetheless, DFS was no different between the SLT-LR and SLT-RFA groups. PLT appears to offer superior long-term oncological outcomes to SLT. Both SLT-LR and SLT-RFA offer acceptable OS and CSS. Further prospective studies are needed to confirm these results, but the re-direction of grafts and transplant philosophy towards PLT rather than SLT may need to be considered.

Laparoscopic Nephrectomy for Massive Kidneys in Polycystic Kidney Disease.

BACKGROUND AND OBJECTIVES: Laparoscopic nephrectomy is now considered a feasible surgical approach, even for large kidneys. In the case of massive kidneys, laparoscopy can be problematic, so that some authors suggest an open approach. However, previous studies have shown that hand-assisted laparoscopic nephrectomy (HALN) may represent a useful compromise.We describe our hand-assisted laparoscopic technique for nephrectomy of large kidneys (> 2500 g) to encourage the use of laparoscopy for nephrectomy in autosomal dominant polycystic kidney disease. METHODS: We retrospectively analyzed data from 26 nephrectomies in 17 patients who underwent HALN for ADPKD and compared them to a group of 22 nephrectomies in 18 patients with open surgical technique. RESULTS: The duration of the procedure was significantly longer in the laparoscopic group, with a median of 180 minutes versus 90 minutes for the unilateral nephrectomies, and 240 minutes versus 122 minutes for the bilateral procedures. The median kidney weight in the open group was 2500 g (range 1300 - 4500 g), while the median weight in the HALN group was 2375 g (range 1000 - 4700 g). The median hospital stay was comparable. No significant differences were recorded in the intra- and postoperative complication rate. CONCLUSION: Hand-assisted laparoscopic nephrectomy can be considered a technique of choice for patients suffering from ADPKD requiring nephrectomy, also with massive kidneys weighing more than 3500 g. Compared to open nephrectomy, HALN can be performed safely, with reasonably longer operating times and without major complications, and offers a significant reduction in hospitalization time, pain and postoperative discomfort.

Long-Term Function of Kidneys From an Acute Renal Failure Donor on Continuous Venovenous Hemofiltration: A Case Report.

The organ shortage has induced many transplant centers to use suboptimal grafts, such as those from expanded criteria donors and donors after cardiac death. Acute renal failure donors, sometimes present in intensive therapy units, have been used in a very low number of cases due to the fear of primary nonfunction of this type of graft. There are few published studies about the utilization of donors with severe acute renal failure and there is no general consensus identifying unequivocal criteria for their use by different transplant centers. We transplanted 2 kidneys from a 67-year-old donor who suffered from acute renal failure as a consequence of extracorporeal circulation in cardiac surgery and died of a massive cerebral edema with cistern obliteration. The kidneys were discarded by other transplant centers due to the patient's acute renal failure, treated by continuous venovenous hemofiltration. Both transplants were successful and both grafts showed very good renal function after 6 months. One recipient suffered from delayed graft function and renal drug toxicity, which resolved 1 month post transplant. The long-term graft function at 10 years is acceptable, with very low proteinuria. As a growing gap between the inadequate supply and constantly high demand for kidney transplantation has led doctors to explore novel policies to increase the number of available organs over the last 2 decades, acute renal failure treated by continuous venovenous hemofiltration does not seem to be a contraindication for the utilization of grafts.

Generalized lymphedema in a sirolimus-treated renal transplant patient.

Generalized lymphedema is an extremely rare effect of sirolimus therapy in renal transplant recipients. We describe the development of this complication in a 56-yr-old woman, who was given an experimental protocol with cyclosporine, sirolimus, steroids, and basiliximab. Following the protocol, after one month, the patient was randomized to the "sirolimus only" group, while cyclosporine was completely suspended and the oral steroids were continued. Three months later, the patient was admitted for severe lymphedema of the lower limbs, with significant weight increase, massive ascites and dyspnea, but excellent renal function. A chest radiography and an ultrasound study of the heart showed a moderate pleural and pericardial effusion. An abdominal ultrasound scan showed two small lymphoceles next to the transplanted kidney, confirmed with a CT scan. After sirolimus discontinuation the generalized lymphedema started to improve and three months later all the symptoms had disappeared.

When a Diuretic Causes Pulmonary Oedema.

BACKGROUND: Hydrochlorothiazide (HCTZ) is one of the most popular drugs for the treatment of hypertension and heart failure. Most of its side effects are harmless and predictable, but some studies report a few life-threatening reactions to this drug, one of the most dangerous being acute pulmonary oedema. CASE REPORT: A 73-year-old woman was admitted to the Emergency Department with acute respiratory failure due to pulmonary oedema. Her past medical history included long-lasting hypertension with permanent atrial fibrillation and mitral stenosis. Her blood pressure control had been suboptimal, so her cardiologist had changed amlodipine to combination therapy with ramipril and HCTZ. However, 20 min after taking the new drug, the patient experienced fever, vomiting and diarrhoea immediately followed by acute onset of dyspnoea. CONCLUSION: Since HCTZ is one of the most popular drugs for hypertension treatment and millions of patients take it every day, it is important to keep in mind both the common adverse reactions as well as the dangerous, although rare, ones. LEARNING POINTS: Pulmonary oedema is a very unusual adverse reaction to hydrochlorothiazide, and a rare presentation of a common condition.Pulmonary oedema is not always due to heart problems.It is important to keep in mind that hypersensitivity reactions may have many different presentations.

Renal transplant from very old donors: how far can we go?

BACKGROUND: The organ shortage has led many transplant centers to accept kidneys from old, suboptimal deceased donors, and make increasing use of old-for-old allocation systems. We report the experience of an Italian transplant center in the utilization of "ultra-old" (>75 years old) donors. METHODS: Sixty grafts from donors aged 75 years or older (mean age 79.1 years, range 75-90 years) were used for 38 patients: 16 as single and 22 as double transplants. RESULTS: The actuarial graft survival rate was 73.7% for year 1, 69.8% for year 2, and 64.0% for year 3. The patient survival rate was 81.2% and remained stable for years 1, 2, and 3. The delayed graft function rate was 57.9%. Acute rejection and chronic allograft nephropathy rates were comparable with our other expanded criteria donors. The majority of the patients had stable creatinine levels, between 2 and 3 mg/mL after the second month, with sufficient creatinine clearance. CONCLUSIONS: Our results seems encouraging with patient and graft survival rates, complication rates, and renal function parameters being slightly worse than in expanded criteria donors, but still generally acceptable. The use of old kidneys in old recipients, bearing in mind their usual life expectancy, gives them a properly functioning kidney and improved quality of life.

Cyclosporin and tacrolimus increase plasma levels of adenosine in kidney transplanted patients.

The immunosuppressive agents, cyclosporin (CsA) and tacrolimus (FK506), display cardioprotective activities. The mechanism would consist on the inhibition of the enzyme, adenosine kinase (AK), leading to an increase in adenosine (ADO) levels. ADO, inosine (INO) and nucleotide plasma levels were measured in kidney transplant recipients before and 1, 2, 4, 6 and 8 h after the administration of CsA or FK506. After CsA and FK506 administration, ADO plasma levels significantly increased, reaching a peak level after 2 h (483 +/- 124 and 429 +/- 96 nm, respectively), and then progressively declined. Calculated peak values (t(max)) of ADO were slightly delayed with respect to those of CsA and FK506. Treatment with rapamycin did not influence the phenomenon. The dynamic profile of plasma changes of ADO, nucleotides and INO were consistent with the inhibition of the enzyme, AK. ADO increase may be clinically relevant in terms of anti-ischaemic, tissue protecting, and immunosuppressive activities as well as in terms of nephrotoxicity.

Massive hemothorax after removal of subclavian vein catheter: a very unusual complication.

A case of massive hemothorax developing a few minutes after removal of a central venous catheter is described in a 51-yr-old woman, who had undergone a renal transplant. The patient had an arteriovenous fistula for hemodialysis on the same side as the central catheter. The mechanism of the onset of this complication is discussed. We recommend avoiding positioning a central catheter on the same side as an arm arteriovenous fistula. Furthermore, we think it is necessary to monitor patients after removal, as is usually done after positioning, to detect this potentially fatal complication.