Update on the reciprocal interference between immunosuppressive therapy and gut microbiota after kidney transplantation

Gut microbiota is often modified after kidney transplantation.This principally happens in the first period after transplantation.Antibiotics and,most of all,immunosuppressive drugs are the main responsible.The relationship between immunosuppressive drugs and the gut microbiota is bilateral.From one side immunosuppressive drugs modify the gut microbiota,often generating dysbiosis;from the other side microbiota may interfere with the immunosuppressant pharmacokinetics,producing products more or less active with respect to the original drug.These phenomena have influence over the graft outcomes and clinical consequences as rejections,infections,diarrhea may be caused by the dysbiotic condition.Corticosteroids,calcineurin inhibitors such as tacrolimus and cyclosporine,mycophenolate mofetil and mTOR inhibitors are the immunosuppressive drugs whose effect on the gut microbiota is better known.In contrast is well known how the gut microbiota may interfere with glucocorticoids,which may be transformed into androgens.Tacrolimus may be transformed by microbiota into a product called M1 that is 15-fold less active with respect to tacrolimus.The pro-drug mycophenolate mofetil is normally transformed in mycophenolic acid that according the presence or not of microbes producing the enzyme glucuronidase,may be transformed into the inactive product.

Predicting outcomes after kidney transplantation: Can Pareto’s rules help us to do so?

Kidney transplantation is the best option for kidney replacement therapy,even considering that most of the times the grafts do not survive as long as their recipients.In the Khalil et al's experience,published in this issue of the Journal,they analyze their second kidney graft survival and describe those significant predictors of early loss.This editorial comments on the results and put in perspective that most of the times,long-term graft survival could be inadvertently jeopardized if the immunosuppressive therapy is reduced or withdrawn for any reason,and that it could happen frequently if the transplant physician intends to innovate with the clinical care without proper evidence-based data.

Challenges to establishing and maintaining kidney transplantation programs in developing countries:What are the coping strategies?

Kidney transplantation(KT)is the optimal form of renal replacement therapy for patients with end-stage renal diseases.However,this health service is not available to all patients,especially in developing countries.The deceased donor KT programs are mostly absent,and the living donor KT centers are scarce.Single-center studies presenting experiences from developing countries usually report a variety of challenges.This review addresses these challenges and the opposing strategies by reviewing the single-center experiences of developing countries.The financial challenges hamper the infrastructural and material availability,coverage of transplant costs,and qualification of medical personnel.The sociocultural challenges influence organ donation,equity of beneficence,and regular follow-up work.Low interests and motives for transplantation may result from high medicolegal responsibilities in KT practice,intense potential psychosocial burdens,complex qualification protocols,and low productivity or compensation for KT practice.Low medical literacy about KT advantages is prevalent among clinicians,patients,and the public.The inefficient organizational and regulatory oversight is translated into inefficient healthcare systems,absent national KT programs and registries,uncoordinated job descriptions and qualification protocols,uncoordinated on-site investigations with regulatory constraints,and the prevalence of commercial KT practices.These challenges resulted in noticeable differences between KT services in developed and developing countries.The coping strategies can be summarized in two main mechanisms:The first mechanism is maximizing the available resources by increasing the rates of living kidney donation,promoting the expertise of medical personnel,reducing material consumption,and supporting the establishment and maintenance of KT programs.The latter warrants the expansion of the public sector and the elimination of non-ethical KT practices.The second mechanism is recruiting external resources,including financial,experience,and training agreements.

Thrombotic microangiopathy after kidney transplantation: Expanding etiologic and pathogenetic spectra

Thrombotic microangiopathy(TMA)is an uncommon but serious complication that not only affects native kidneys but also transplanted kidneys.This review is specifically focused on post-transplant TMA(PT-TMA)involving kidney transplant recipients.Its reported prevalence in the latter population varies from 0.8%to 14%with adverse impacts on both graft and patient survival.It has many causes and associations,and the list of etiologic agents and associations is growing constantly.The pathogenesis is equally varied and a variety of pathogenetic pathways lead to the development of microvascular injury as the final common pathway.PT-TMA is categorized in many ways in order to facilitate its management.Ironically,more than one causes are contributory in PT-TMA and it is often difficult to pinpoint one particular cause in an individual case.Pathologically,the hallmark lesions are endothelial cell injury and intravascular thrombi affecting the microvasculature.Early diagnosis and classification of PT-TMA are imperative for optimal outcomes but are challenging for both clinicians and pathologists.The Banff classification has addressed this issue and has developed minimum diagnostic criteria for pathologic diagnosis of PT-TMA in the first phase.Management of the condition is also challenging and still largely empirical.It varies from simple maneuvers,such as plasmapheresis,drug withdrawal or modification,or dose reduction,to lifelong complement blockade,which is very expensive.A thorough understanding of the condition is imperative for an early diagnosis and quick treatment when the treatment is potentially effective.This review aims to increase the awareness of relevant stakeholders regarding this important,potentially treatable but under-recognized cause of kidney allograft dysfunction.

Values of Donor Serum Lipids and Calcium in Predicting Graft Function after Kidney Transplantation:A Retrospective Study

Objective Delayed graft function(DGF)and early graft loss of renal grafts are determined by the quality of the kidneys from the deceased donor.As“non-traditional”risk factors,serum biomarkers of donors,such as lipids and electrolytes,have drawn increasing attention due to their effects on the postoperative outcomes of renal grafts.This study aimed to examine the value of these serum biomarkers for prediction of renal graft function.Methods The present study consecutively collected 306 patients who underwent their first single kidney transplantation(KT)from adult deceased donors in our center from January 1,2018 to December 31,2019.The correlation between postoperative outcomes[DGF and abnormal serum creatinine(SCr)after 6 and 12 months]and risk factors of donors,including gender,age,body mass index(BMI),past histories,serum lipid biomarkers[cholesterol,triglyceride,high-density lipoprotein(HDL)and low-density lipoprotein(DL)],and serum electrolytes(calcium and sodium)were analyzed and evaluated.Results(1)Donor age and pre-existing hypertension were significantly correlated with the incidence rate of DGF and high SCr level(≥2 mg/dL)at 6 and 12 months after KT(P<0.05);(2)The donor’s BMI was significantly correlated with the incidence rate of DGF after KT(P<0.05);(3)For serum lipids,merely the low level of serum HDL of the donor was correlated with the reduced incidence rate of high SCr level at 12 months after KT[P<0.05,OR(95%CI):0.425(0.202–0.97)];(4)The serum calcium of the donor was associated with the reduced incidence rate of high SCr level at 6 and 12 months after KT[P<0.05,OR(95%CI):0.184(0.045–0.747)and P<0.05,OR(95%CI):0.114(0.014–0.948),respectively].Conclusion The serum HDL and calcium of the donor may serve as predictive factors for the postoperative outcomes of renal grafts after KT,in addition to the donor’s age,BMI and pre-existing hypertension.

Preemptive living donor kidney transplantation:Access,fate,and review of the status in

BACKGROUND Preemptive living donor kidney transplantation(PLDKT)is recommended as the optimal treatment for end-stage renal disease.AIM To assess the rate of PLDKT among patients who accessed KT in our center and review the status of PLDKT in Egypt.METHODS We performed a retrospective review of the patients who accessed KT in our center from November 2015 to November 2022.In addition,the PLDKT status in Egypt was reviewed relative to the literature.RESULTS Of the 304 patients who accessed KT,32 patients(10.5%)had preemptive access to KT(PAKT).The means of age and estimated glomerular filtration rate were 31.7±13 years and 12.8±3.5 mL/min/1.73 m2,respectively.Fifty-nine patients had KT,including 3 PLDKTs only(5.1%of total KTs and 9.4%of PAKT).Twenty-nine patients(90.6%)failed to receive PLDKT due to donor unavailability(25%),exclusion(28.6%),regression from donation(3.6%),and patient regression on starting dialysis(39.3%).In multivariate analysis,known primary kidney disease(P=0.002),patient age(P=0.031)and sex(P=0.001)were independent predictors of achievement of KT in our center.However,PAKT was not significantly(P=0.065)associated with the achievement of KT.Review of the literature revealed lower rates of PLDKT in Egypt than those in the literature.CONCLUSION Patient age,sex,and primary kidney disease are independent predictors of achieving living donor KT.Despite its non-significant effect,PAKT may enhance the low rates of PLDKT.The main causes of non-achievement of PLDKT were patient regression on starting regular dialysis and donor unavailability or exclusion.

Gastrointestinal manifestations of long-term effects after COVID-19 infection in patients with dialysis or kidney transplantation:An observational cohort study

BACKGROUND Prolonged symptoms after corona virus disease 2019(Long-COVID) in dialysisdependent patients and kidney transplant(KT) recipients are important as a possible risk factor for organ dysfunctions,especially gastrointestinal(GI)problems,during immunosuppressive therapy.AIM To identify the characteristics of GI manifestations of Long-COVID in patients with dialysis-dependent or KT status.METHODS This observational,prospective study included patients with COVID-19 infection,confirmed by reverse transcription polymerase chain reaction,with the onset of symptoms between 1 January 2022 and 31 July 2022 which was explored at 3 mo after the onset,either through the out-patient follow-up or by telephone interviews.RESULTS The 645 eligible participants consisted of 588 cases with hemodialysis(HD),38 patients with peritoneal dialysis(PD),and 19 KT recipients who were hospitalized with COVID-19 infection during the observation. Of these,577(89.5%) cases agreed to the interviews,while 64(10.9%)patients with HD and 4(10.5%) cases of PD were excluded. The mean age was 52 ± 11 years with 52% women. The median dialysis duration was 7 ± 3 and 5 ± 1 years for HD and PD groups,respectively,and the median time post-transplantation was 6 ± 2 years. Long-COVID was identified in 293/524(56%) and 21/34(62%) in HD and PD,respectively,and 7/19(37%) KT recipients. Fatigue was the most prevalent(96%) of the non-GI tract symptoms,whereas anorexia(90.9%),loss of taste(64.4%),and abdominal pain(62.5%) were the first three common GI manifestations of Long-COVID. Notably,there were 6 cases of mesenteric panniculitis from 19patients with GI symptoms in the KT group.CONCLUSION Different from patients with non-chronic kidney disease,there was a high prevalence of GI manifestations of Long-COVID in dialysis-dependent patients and KT recipients. An appropriate long-term follow-up in these vulnerable populations after COVID-19 infection is possibly necessary.

Shifting perspectives in liver diseases after kidney transplantation

Liver diseases after kidney transplantation range from mild biochemical abnormalities to severe hepatitis or cirrhosis.The causes are diverse and mainly associated with hepatotropic viruses,drug toxicity and metabolic disorders.Over the past decade,the aetiology of liver disease in kidney recipients has changed significantly.These relates to the use of direct-acting antiviral agents against hepatitis C virus,the increasing availability of vaccination against hepatitis B and a better understanding of drug-induced hepatotoxicity.In addition,the emergence of the severe acute respiratory syndrome coronavirus 2 pandemic has brought new challenges to kidney recipients.This review aims to provide healthcare professionals with a comprehensive understanding of recent advances in the management of liver complications in kidney recipients and to enable them to make informed decisions regarding the risks and impact of liver disease in this population.

Successful treatment of a case of COVID-19 pneumonia following kidney transplantation using paxlovid and tocilizumab

BACKGROUND Since its initial detection in 2019,coronavirus disease 2019(COVID-19)pneumonia has rapidly spread throughout the world in a global pandemic.However,reports of COVID-19 pneumonia among patients following kidney transplantation have been limited and no uniform treatment guidelines for these patients have yet to be established.CASE SUMMARY Here,we report the case of a 39-year-old patient recovering from kidney transplantation who contracted perioperative COVID-19 pneumonia that was successfully controlled with oral paxlovid and a single intravenous drip infusion of tocilizumab following the discontinuation of immunosuppressive drugs.CONCLUSION Given the rapid spread of severe acute respiratory syndrome coronavirus 2 infections,clinicians should be aware of the potential for more cases of COVID-19 among patients following kidney transplantation and be familiar with appropriate treatment options and likely clinical outcomes.

Diagnosis and treatment of Whipple disease after kidney transplantation:A case report

BACKGROUND Kidney transplantation is the standard treatment for end-stage renal disease.Particularly,rare and specific pathogenic infections which are asymptomatic are often difficult to diagnose,causing delayed and ineffective treatment and thus seriously affecting prognosis.Tropheryma whipplei(T.whipplei)is a Gram-positive actinomycete widely found in soil,sewage,and other external environments and is present in the population as an asymptomatic pathogen.There is relatively little documented research on T.whipplei in renal transplant patients,and there are no uniform criteria for treating this group of post-transplant patients.This article describes the treatment of a 42-year-old individual with post-transplant T.whipplei infection following kidney transplantation.CASE SUMMARY To analyze clinical features of Whipple’s disease and summarize its diagnosis and treatment effects after renal transplantation.Clinical data of a Whipple’s disease patient treated in the affiliated hospital of Guizhou Medical University were collected and assessed retrospectively.The treatment outcomes and clinical experience were then summarized via literature review.The patient was admitted to the hospital due to recurrent diarrhea for 1 mo,shortness of breath,and 1 wk of fever,after 3 years of renal transplantation.The symptoms of the digestive and respiratory systems were not significantly improved after adjusting immunosuppressive regimen and anti-diarrheal,empirical antibiotic treatments.Bronchoscopic alveolar fluid was collected for meta-genomic next-generation sequencing(mNGS).The deoxyribonucleic acid sequence of Tropheryma whipplei was detected,and Whipple’s disease was diagnosed.Meropenem,ceftriaxone,and other symptomatic treatments were given,and water-electrolyte balance was maintained.Symptoms resolved quickly,and the patient was discharged after 20 d of hospitalization.The compound sulfamethoxazole tablet was continued for 3 mo after discharge.No diarrhea,fever,and other symptoms occurred during the 6-month follow-up.CONCLUSION Whipple’s disease is rare,with no specific symptoms,which makes diagnosis difficult.Polymerase chain reaction or mNGS should be immediately performed when the disease is suspected to confirm the diagnosis.

Efficacy and safety of local candida immunotherapy in recalcitrant warts in pediatric kidney transplantation:A case report

BACKGROUND Warts are common in recipients of kidney transplantation(KT).Resistant warts which are not amenable to conventional therapies may lead to significant morbidity.Limited data exists on safety and efficacy of local immunotherapy among immunocompromised KT recipients.CASE SUMMARY We report a seven-year-old child who presented with recalcitrant plantar periungual warts in the early KT period.Immunosuppression consisted of tacrolimus,mycophenolate and steroid.Due to failure of conventional anti-wart therapies,he was treated with two sessions of intralesional(IL)candida immunotherapy along with liquid nitrogen cryotherapy leading to complete resolution of the warts.Interestingly,de novo BK viremia was seen about three weeks following the last candida immunotherapy.This required reduction of immunosuppression and other anti-BK viral therapies.Allograft function remained stable but there were donor specific antibodies detected.There also was elevated level of plasma donor derived cell-free DNA.A pneumocystis jirovecii pneumonia occurred ten months following completion of immunotherapy that was successfully treated with trimethoprim-sulfamethoxazole.During this ten-month follow-up period,there have been no recurrence of warts,and transplant kidney function has remained stable.CONCLUSION Stimulation of cell-mediated immunity against the human papilloma virus induced by the IL candida immunotherapy is thought to be a cause for wart resolution.With this therapy,whether it is necessary to augment the immunosuppression to prevent rejection is unclear as that may come with a risk of infectious complications.Larger,prospective studies in pediatric KT recipients are needed to explore these important issues.

Infertility,pregnancy and breastfeeding in kidney transplantation recipients:Key issues

Chronic kidney disease(CKD),especially in advanced stages,is an important cause of infertility.In CKD patients,infertility has been linked to multiple factors.The pathophysiology of infertility related to CKD is complex and forked.Correction of modifiable factors can improve fertility in both genders.In males as well as females,successful kidney transplantation offers good chances of restoration of reproductive function.In female renal allograft recipients,recovery of reproductive functions in the post-transplant period will manifest as restoration of normal menses and ovulation.Owing to this improvement,there is a significant risk of unplanned pregnancy,hence the need to discuss methods of contraception before transplantation.In kidney transplant recipients,different contraceptive options for pregnancy planning,have been used.The selection of one contraception over another is based on preference and tolerability.Pregnancy,in renal transplanted females,is associated with physiologic changes that occur in pregnant women with native kidneys.Immunosuppressive medications during pregnancy,in a recipient with a single functioning kidney,expose the mother and fetus to unwanted complications.Some immunosuppressive drugs are contraindicated during pregnancy.Immunosuppressive medications should be discussed with renal transplant recipients who are planning to breastfeed their babies.In addition to antirejection drugs,other medications should be managed accordingly,whenever pregnancy is planned.

Predictors of graft function and survival in second kidney transplantation: A single center experience

BACKGROUND The increasing kidney retransplantation rate has created a parallel field of research,including the risk factors and outcomes of this advanced form of renal replacement therapy.The presentation of experiences from different kidney transplantation centers may help enrich the literature on kidney retransplantation,as a specific topic in the field of kidney transplantation.AIM To identify the risk factors affecting primary graft function and graft survival rates after second kidney transplantation(SKT).METHODS The records of SKT cases performed between January 1977 and December 2014 at a European tertiary-level kidney transplantation center were retrospectively reviewed and analyzed.Beside the descriptive characteristics,the survivals of patients and both the first and second grafts were described using Kaplan-Meier curves.In addition,Kaplan-Meier analyses were also used to estimate the survival probabilities at 1,3,5,and 10 post-operative years,as well as at the longest followup duration available.Moreover,bivariate associations between various predictors and the categorical outcomes were assessed,using the suitable biostatistical tests,according to the predictor type.RESULTS Out of 1861 cases of kidney transplantation,only 48 cases with SKT were eligible for studying,including 33 men and 15 women with a mean age of 42.1±13 years.The primary non-function(PNF)graft occurred in five patients(10.4%).In bivariate analyses,a high body mass index(P=0.009)and first graft loss due to acute rejection(P=0.025)were the only significant predictors of PNF graft.The second graft survival was reduced by delayed graft function in the first(P=0.008)and second(P<0.001)grafts.However,the effect of acute rejection within the first year after the first transplant did not reach the threshold of significance(P=0.053).The mean follow-up period was 59.8±48.6 mo.Censored graft/patient survival rates at 1,3,5 and 10 years were 90.5%/97.9%,79.9%/95.6%,73.7%/91.9%,and 51.6%/83.0%,respectively.CONCLUSION Non-immediate recovery modes of the first and second graft functions were significantly associated with unfavorable second graft survival rates.Patient and graft survival rates of SKT were similar to those of the first kidney transplantation.

Liver transplantation as an alternative for the treatment of intrahepatic cholangiocarcinoma: Past, present, and future directions

Intrahepatic cholangiocarcinoma(iCCA)is a rare biliary tract cancer with high mortality rate.Complete resection of the iCCA lesion is the first choice of treatment,with good prognosis after margin-negative resection.Unfortunately,only 12%-40% of patients are eligible for resection at presentation due to cirrhosis,portal hypertension,or large tumor size.Liver transplantation(LT)offers margin-negative iCCA extirpation for patients with unresectable tumors.Initially,iCCA was a contraindication for LT until size-based selection criteria were introduced to identify patients with satisfied post-LT outcomes.Recent studies have shown that tumor biology-based selection can yield high post-LT survival in patients with locally advanced iCCA.Another selection criterion is the tumor response to neoadjuvant therapy.Patients with response to neoadjuvant therapy have better outcomes after LT compared with those without tumor response to neoadjuvant therapy.Another index that helps predict the treatment outcome is the biomarker.Improved survival outcomes have also opened the door for living donor LT for iCCA.Patients undergoing LT for iCCA now have statistically similar survival rates as patients undergoing resection.The combination of surgery and locoregional and systemic therapies improves the prognosis of iCCA patients.

The Relationship between the intolerance of uncertainty and the fear of COVID-19 in patients awaiting kidney transplantation during the pandemic

Objective:This study aims to identify the relationship between the intolerance of uncertainty and the fear of COVID-19 in patients awaiting kidney transplantation during the COVID-19 pandemic.Methods:This descriptive and cross-sectional study was performed with the participation of 355 individuals.The data were collected with a patient information form,the intolerance of uncertainty scale–short form(IUS),and the fear of COVID-19 scale(FCV-19S).Results:The mean IUS–short form score of the participants was 53.03±5.11,and their mean FCV-19S score was 30.62±4.10.A statistically highly significant positive relationship was identified between the FCV-19S and IUS scores of the participants(r:0.850;P<0.001).Conclusion:As the patients’intolerance of uncertainty increased,their fears of COVID-19 also increased.For patients awaiting kidney transplantation during the COVID-19 pandemic,which is full of challenges,to cope with fear and uncertainty,it is recommended that patients are provided with care with a multidisciplinary team approach.

Association of physical activity with risk of chronic kidney disease in China:A population-based cohort study

Background:Information on the association between physical activity(PA)and the risk of chronic kidney disease(CKD)is limited.We aimed to explore the associations of total,domain-specific,and intensity-specific PA with CKD and its subtypes in China.Methods:The study included 475,376 adults from the China Kadoorie Biobank aged 30-79 years during 2004-2008 at baseline.An interviewer-administered questionnaire was used to collect the information about PA,which was quantified as metabolic equivalent of task hours per day(MET-h/day)and categorized into 4 groups based on quartiles.Cox regression was used to analyze the association between PA and CKD risk.Results:During a median follow-up of 12.1 years,5415 incident CKD cases were documented,including 1159 incident diabetic kidney disease(DKD)cases and 362 incident hypertensive nephropathy(HTN)cases.Total PA was inversely associated with CKD risk,with an adjusted hazard ratio(HR,95%confidence interval(95%CI))of 0.83(0.75-0.92)for incident CKD in the highest quartile of total PA as compared with participants in the lowest quartile.Similar results were observed for risk of DKD and HTN,and the corresponding HRs(95%CIs)were 0.75(0.58-0.97)for DKD risk and 0.56(0.37-0.85)for HTN risk.Increased nonoccupational PA,low-intensity PA,and moderate-to-vigorous-intensity PA were significantly associated with a decreased risk of CKD,with HRs(95%CIs)of 0.80(0.73-0.88),0.85(0.77-0.94),and 0.85(0.76-0.95)in the highest quartile,respectively.Conclusion:PA,including nonoccupational PA,low-intensity PA,and moderate-to-vigorous-intensity PA,was inversely associated with the risk of CKD,including DKD,HTN,and other CKD,and such associations were dose dependent.

Pleural empyema with endobronchial mass due to Rhodococcus equi infection after renal transplantation: A case report and review of literature

BACKGROUND Kidney transplantation is the best option for patients with end-stage renal disease.However,the need for lifelong immunosuppression results in renal transplant recipients being susceptible to various infections.Rhodococcus equi(R.equi)is a rare opportunistic pathogen in humans,and there are limited reports of infection with R.equi in post-renal transplant recipients and no uniform standard of treat-ment.This article reports on the diagnosis and treatment of a renal transplant recipient infected with R.equi 21 mo postoperatively and summarizes the charac-teristics of infection with R.equi after renal transplantation,along with a detailed review of the literature.Here,we present the case of a 25-year-old man who was infected with R.equi 21 mo after renal transplantation.Although the clinical features at the time of presentation were not specific,chest computed tomography(CT)showed a large volume of pus in the right thoracic cavity and right middle lung atelectasis,and fiberoptic bronchoscopy showed an endobronchial mass in the right middle and lower lobe orifices.Bacterial culture and metagenomic next-generation sequen-cing sequencing of the pus were suggestive of R.equi infection.The immunosup-pressive drugs were immediately suspended and intravenous vancomycin and azithromycin were administered,along with adequate drainage of the abscess.The endobronchial mass was then resected.After the patient’s clinical symptoms and chest CT presentation resolved,he was switched to intravenous ciprofloxacin and azithromycin,followed by oral ciprofloxacin and azithromycin.The patient was re-hospitalized 2 wk after discharge for recurrence of R.equi infection.He recovered after another round of adequate abscess drainage and intravenous ciprofloxacin and azithromycin.CONCLUSION Infection with R.equi in renal transplant recipients is rare and complex,and the clinical presentation lacks specificity.Elaborate antibiotic therapy is required,and adequate abscess drainage and surgical excision are necessary.Given the recurrent nature of R.equi,patients need to be followed-up closely.

Liver transplantation as an alternative for the treatment of perihilar cholangiocarcinoma: A critical review

Background:Perihilar cholangiocarcinoma(phCCC)is a dismal malignancy.There is no consensus regard-ing the best treatment for patients with unresectable phCCC.The present review aimed to gather the current pieces of evidence for liver transplantation and liver resection as a treatment for phCCC and to build better guidance for clinical practice.Data sources:The search was conducted in PubMed,Embase,Cochrane,and LILACS.The related references were searched manually.Inclusion criteria were:reports in English or Portuguese literature that a)patients with confirmed diagnosis of phCCC;b)patients treated with a curative intent;c)patients with the outcomes of liver resection and liver transplantation.Case reports,reviews,letters,editorials,conference abstracts and papers with full-text unavailability were excluded from the analysis.Results:Most of the current literature is based on observational retrospective studies with low grades of evidence.Liver resection has better long-term outcomes than systemic chemotherapy or palliation ther-apy and liver transplantation is a good alternative for selected patients with unresectable phCCC.All candidates for resection or transplantation should be medically fit and free of intrahepatic or extrahep-atic diseases.As a general rule,patients presenting with a tumor having a longitudinal size>3 cm or extending below the cystic duct,lymph node disease,confirmed extrahepatic dissemination;intraoper-atively diagnosed metastatic disease;a history of other malignancies within the last five years,and did not complete chemoradiation regimen and were medically unfit should not be considered for transplan-tation.Some of these criteria should be individually assessed.Liver transplantation or resection should only be considered in highly experienced hepatobiliary centers,and any decision-making must be based on a multidisciplinary evaluation.Conclusions:phCCC is a complex condition with high morbidity.Surgical therapies,including hepatec-tomy and liver transplantation,are the best option for better long-term disease-free survival.

Acute pancreatitis as a complication of acute COVID-19 in kidney transplant recipients

BACKGROUND Acute pancreatitis is a rare extrapulmonary manifestation of coronavirus disease 2019(COVID-19)but its full correlation with COVID-19 infection remains unknown.AIM To identify acute pancreatitis’occurrence,clinical presentation and outcomes in a cohort of kidney transplant recipients with acute COVID-19.METHODS A retrospective observational single-centre cohort study from a transplant centre in Croatia for all adult renal transplant recipients with a functioning kidney allograft between March 2020 and August 2022 to record cases of acute pancreatitis during acute COVID-19.Data were obtained from hospital electronic medical records.Severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)infection was proven by a positive SARS-CoV-2 real-time reverse transcriptase-polymerase chain reaction on the nasopharyngeal swab.RESULTS Four hundred and eight out of 1432(28.49%)patients who received a renal allograft developed COVID-19 disease.The analyzed cohort included 321 patients(57%males).One hundred and fifty patients(46.7%)received at least one dose of the anti-SARS-CoV-2 vaccine before the infection.One hundred twenty-five(39.1%)patients required hospitalization,141(44.1%)developed pneumonia and four patients(1.3%)required mechanical ventilation.Treatment included immunosuppression modification in 233 patients(77.1%)and remdesivir in 53 patients(16.6%),besides the other supportive measures.In the study cohort,only one transplant recipient(0.3%)developed acute pancreatitis during acute COVID-19,presenting with abdominal pain and significantly elevated pancreatic enzymes.She survived without complications with a stable kidney allograft function.CONCLUSION Although rare,acute pancreatitis may complicate the course of acute COVID-19 in kidney transplant recipients.The mechanism of injury to the pancreas and its correlation with the severity of the COVID-19 infection in kidney transplant recipients warrants further research.

Simultaneous pancreas-kidney transplantation for end-stage renal failure in type 1 diabetes mellitus: Current perspectives

Type 1 diabetes mellitus(T1DM)is one of the important causes of chronic kidney disease(CKD)and end-stage renal failure(ESRF).Even with the best available treatment options,management of T1DM poses significant challenges for clinicians across the world,especially when associated with CKD and ESRF.Substantial increases in morbidity and mortality along with marked rise in treatment costs and marked reduction of quality of life are the usual consequences of onset of CKD and progression to ESRF in patients with T1DM.Simultaneous pancreas-kidney transplant(SPK)is an attractive and promising treatment option for patients with advanced CKD/ESRF and T1DM for potential cure of these diseases and possibly several complications.However,limited availability of the organs for transplantation,the need for long-term immunosuppression to prevent rejection,peri-and post-operative complications of SPK,lack of resources and the expertise for the procedure in many centers,and the cost implications related to the surgery and postoperative care of these patients are major issues faced by clinicians across the globe.This clinical update review compiles the latest evidence and current recommendations of SPK for patients with T1DM and advanced CKD/ESRF to enable clinicians to care for these diseases.