Management strategies for common viral infections in pediatric renal transplant recipients

Viral infections have been considered as a major cause of morbidity and mortality after kidney transplantation in pediatric cohort.Children are at high risk of acquiring virus-related complications due to immunological immaturity and the enhanced alloreactivity risk that led to maintenance of high immunosuppressive regimes.Hence,prevention,early detection,and prompt treatment of such infections are of paramount importance.Among all viral infections,herpes viruses(herpes simplex virus,varicella zoster virus,Epstein-Barr virus,cytomegalovirus),hepatitis B and C viruses,BK polyomavirus,and respiratory viruses(respiratory syncytial virus,parainfluenza virus,influenza virus and adenovirus)are common in kidney transplant recipients.These viruses can cause systemic disease or allograft dysfunction affecting the clinical outcome.Recent advances in technology and antiviral therapy have improved management strategies in screening,monitoring,adoption of prophylactic or preemptive therapy and precise treatment in the immunocompromised host,with significant impact on the outcome.This review discusses the etiology,screening and monitoring,diagnosis,prevention,and treatment of common viral infections in pediatric renal transplant recipients.

Bilateral Avascular Necrosis of the Femoral Head in Renal Transplant Recipient: A Case Report

Osteoarticular complications are common after renal transplantation. The complications may result from the bone condition prior to transplantation or the iatrogenic effects of the treatments administered. These complications lead to significant morbidity and mortality, in addition to chronic pain and functional impairment. We report the clinical case of bilateral avascular necrosis (AVN) of the femoral head in a kidney transplant recipient. Clinical Case: 53-year-old male with a history of chronic hypertension. He underwent chronic hemodialysis for 12 months and was treated with Entecavir for chronic hepatitis B. The patient received a kidney transplant from a non-related living donor. Induction therapy included Thymoglobulin along with tapered corticosteroids, reaching a dose of 5 mg/day after 3 months, Mycophenolate mofetil (2 g/day), and Tacrolimus adjusted based on residual levels. There was good recovery of renal graft function. After six months, the patient reported bilateral hip pain and functional impairment of both lower limbs. Pelvic X-rays showed signs suggestive of bilateral AVN of the femoral heads. The diagnosis was confirmed by MRI. The patient underwent right hip drilling and total left hip replacement (THR). A right THR was performed a year later. Conclusion: AVN constitutes a frequent cause of morbidity and mortality after RT. The pathophysiology of osteonecrosis remains complex and multifactorial. We emphasize the importance of conducting a thorough assessment of bone health in patients both before and after RT.

Risk stratification of renal transplant recipients using routine parameters: Implication of learning from SARS-CoV-2 into transplant follow-up program

BACKGROUND Severe acute respiratory syndrome coronavirus-2(SARS-CoV-2)infection is a global pandemic that is associated with a high risk of morbidity and mortality among recipients of solid organ transplantation.In the course of acute SARS-CoV-2 infection,various laboratory markers have been identified as predictors for high risk of mortality.AIM To risk stratify renal transplant recipients(RTxR)using general demographic parameters,comorbidities and routine laboratory markers for the severity of the disease and its outcomes.We believe that learning about these routinely monitored parameters can help us plan better strategies for the RTxR follow-up program.METHODS This present study includes RTxR who acquired SARS-CoV-2 infection from March 2020 to February 2021.We recorded the basic demographics,comorbidities and routine laboratory markers.We investigated the impact of SARS-CoV-2 infection on RTxRs and risk-stratified the progression of disease severity and outcomes in terms of recovery or mortality.RESULTS From 505 RTxRs in our renal transplant follow-up program,29(7.75%)RTxRs had PCR-positive SARS-CoV-2 infection.We recorded 8 deaths from SARS-CoV-2 infection giving an overall mortality rate of 1.6%but a significant 27.6%mortality in SARS-CoV-2 positive recipients.Age more than 68 years,non-Caucasian ethnicity and male gender were associated with a significant drop in survival probability;P≤0.001.<0.001 and<0.0001 respectively.87.5%of the deceased were diabetic;P≤0.0.0001.Estimated glomerular filtration rate of less than 26 mL/min/1.73 m2,serum albumin less than 20 g/L,Hemoglobin less than 9.6 g/L and serum calcium less than 1.70 mmol/L were all associated with significantly increased risk of mortality;P=0.0128,<0.001,<0.0001 and 0.0061 respectively.CONCLUSION This study has identified some routinely used modifiable parameters in predicting a higher risk of mortality and morbidity.This knowledge can be used in RTxR follow-up programs by addressing these parameters early to help reduce the morbidity and mortality in RTxRs.

Morphological characteristics of spermatozoa before and after renal transplantation

Aim: To investigate the changes of the spermatozoa ultrastructures before and after renal transplantation in uremic patients. Methods: The sperm of five uremic patients before and after transplantation and four healthy volunteers were collected and examined by scanning electron microscopy. Results: Abnormal spermatozoa were found in patients pre-transplantation; abnormalities included deletion of the acrosome, absence of the postacrosomal and postnuclear ring, dumbbell-like changes of the head, tail curling, and absence of the mitochondrial sheath in the mid-segment. After renal transplantation, most of the spermatozoa became normal. Conclusion: There are many abnormalities with regard to the appearance and structure of the head, acrosome, mitochondria and tail of the spermatozoa in uremic patients. The majority of the spermatozoa returned to normal after renal transplantation, but a few still presented some abnormalities possibly relating to the administration of immunosuppressants.

Hepatitis B virus infection and renal transplantation

Although the prevalence of chronic hepatitis B virus (HBV) infection has declined in renal transplant recipients (RTRs), it remains a relevant clinical problem with high morbidity and mortality in long-term follow up. A thorough evaluation, including liver biopsy as well as assessment of HBV replication in serum (i.e. hepatitis B e antigen and/or HBV DNA) is required before transplantation. Interferon should not be used in this setting because of low efficacy and precipitation on acute allograft rejection. The advent of effective antiviral therapies offers the opportunity to prevent the progression of liver disease after renal transplantation. However, as far as we are aware, no studies have compared prophylactic and preemptive strategies. To date, the majority of RTRs with HBV-related liver disease have had a high virological and biochemical response to lamivudine use. However, lamivudine resistance is frequent with a prolonged course of therapy. Considering long-term treatment, antiviral agents with a high genetic barrier to resistance and lack of nephrotoxicity are suggested. The optimal strategy in RTRs with HBV infection remains to be established in the near future.

Reliability and validity of the Chinese version of CAHS among renal transplant recipients

Purpose:The purpose of this study was to assess the applicability of the Chinese version of Cognitive Appraisal of Health Scale(CAHS)for renal transplant recipients,and to make a preliminary evaluation of its reliability and validity.Methods:A total of 147 renal transplant recipients who attended a transplant follow-up clinic in a Level 3,Grade A hospital in Beijing were asked to complete the Chinese version of CAHS.Following completion the reliability and validity of the scale were tested.Results:The Cronbach alpha coefficient of Chinese version of CAHS among subscales of threat,harm,challenge and benign-irrelevant were 0.857,0.806,0.680,0.100 respectively;and the test-retest reliability coefficient were 0.791,0.601,0.624,0.470(p<0.01).Spearman correlation was used to test the four subscales'correlation between the item score and the total score,in which threat was 0.598e0.748,challenge was 0.517e0.651,harm was 0.528 e0.735 and benign-irrelevant was 0.507e0.651.These correlations were all statistically significant.The four common factors were extracted using factor analysis.The four factors accounted for 50.356%of the total variance.The SF-36 Physical Component Summary(PCS)and Mental Component Summary(MCS)scores were correlated with each subscale score in CAHS.Threat was weakly correlated to PCS,and was moderately correlated to MCS;harm was moderately correlated to both PCS and MCS;challenge was weakly correlated to both PCS and MCS and benign-irrelevant did not correlate with neither PCS nor MCS.The Chinese version of CAHS has been shown to have good discriminate and convergent validity.Conclusion:The Chinese version of the CAHS was supported to be applicable and to provide measurable performance in renal transplant recipients,thus it can be utilized with renal transplant recipients in China.

The clinical value of enzyme-multiplied immunoassay technique monitoring the plasma concentrations of cyclosporine A after renal transplantation

The feasibility and the clinical value of the enzyme-multiplied immunoassay technique （EMIT） monitoring of blood concentrations of cyclosporine A （CsA） in patients treated with CsA were investigated after kidney transplantation. The validation method was performed to the EMIT determination of CsA blood concentration, the CsA whole blood trough concentrations （Co） of patients in different time periods after renal transplantation were monitored, and combined with the clinical complications, the statistical results were analyzed and compared. EMIT was precise, accurate and stable, also with a high quality control. The mean postoperative blood concentration of CsA was as follows： 〈1 month, （281.4± 57.9）ng/mL; 2 - 3 months, （264.5 ± 41.2） ng/mL; 4 - 5 months, （236.4 ± 38.9） ng/mL; 6 - 12 months, （206.5± 32.6）ng/mL; 〉12 months, （185.6± 28.1）ng/mL. The toxic reaction rate of CsA blood concentration within the recommended therapeutic concentration was 14.1%, significantly lower than that of the none-recommended dose group （37.2%） （P〈0.05）; the transplantation rejection rate was 4.4%, significantly lower than that of the none- recommended dose group （22.5%） （P〈0.05）. Using EMIT to monitor the blood concentration of CsA as the routine laboratory method is feasible, and is able to reduce the CsA toxicity and rejection significantly, leading to achieving the desired therapeutic effect.

Fatal visceral disseminated varicella-zoster virus infection in a renal transplant recipient:A case report

BACKGROUND Visceral disseminated varicella-zoster virus(VZV)infection is a rare but lifethreatening disease.In transplant recipients with VZV infection,visceral dissemination may develop without skin eruptions,which leads to the failure of early diagnosis.CASE SUMMARY The patient was a 33-year-old male renal recipient who was referred to our hospital with severe upper abdominal pain of 3-d duration.On admission,the patient rapidly developed septic shock and multiple organ dysfunction syndrome with liver dysfunction and acute kidney injury.Next-generation sequencing of peripheral blood yielded 39224 sequence reads of VZV,and real-time polymerase chain reaction for VZV was positive,with 1.2×10^(7) copies/mL.The final diagnosis was visceral disseminated VZV infection.Acyclovir and supportive therapy were started,but the patient died of severe visceral organ damage 16 h after admission.CONCLUSION Visceral disseminated VZV infection is possible in renal transplant recipients presenting abdominal pain and rapidly-evolving organ damage without skin involvement.

Ultrasound Assessraent of Intima-media Thickness and Diameter of Carotid Arteries in Patients Undergoing Hemodialysis or Renal Transplantation

Renal transplant （RT） recipients have a high risk of developing cardiovascular diseases. However, the effects of renal transplantation on the development of arteriosclerosis have been controversial. The carotid intima-media thickness （CIMT） and diameter （CD） are important indicators of vascular remodeling and arteriosclerosis. In this study, 31 patients with hemodialysis （HD）, 31 RT recipients and 84 age- and gender-matched control subjects were enrolled. Their CIMT and CD were measured by ultrasonic radiofrequency tracking, and the linear regression models and Z test were used to identify the progression of arteriosclerosis and the risk factors. Compared with HD group, RT group had significantly lower CIMT and CD. CIMT was found to be associated with age, body weight, resistance index and diastolic velocity, while CD was associated significantly with age, body weight, pulsatility index, end diastolic velocity and diastolic blood pressure （DBP）, respectively. The correlation curves between CIMT and age showed the slopes of curves were decreased successively in control, RT and HD groups, and the curves between CD and age showed the slopes were decreased in order of RT 〉 control 〉 HD groups. It was concluded that CIMT and CD were significantly correlated with age in RT and moderately with age in HD patients. RT could reduce the progress of arteriosclerosis in patients with end-stage renal disease.

Diagnosis and management of ureteral complications following renal transplantation

When compared with maintenance dialysis,renal transplantation affords patients with end-stage renal disease better long-term survival and a better quality of life.Approximately 9% of patients will develop a major urologic complication following kidney transplantation.Ureteral complications are most common and include obstruction(intrinsic and extrinsic),urine leak and vesicoureteral reflux.Ureterovesical anastomotic strictures result from technical error or ureteral ischemia.Balloon dilation or endoureterotomy may be considered for short,low-grade strictures,but open reconstruction is associated with higher success rates.Urine leak usually occurs in the early postoperative period.Nearly 60% of patients can be successfully managed with a pelvic drain and urinary decompression(nephrostomy tube,ureteral stent,and indwelling bladder catheter).Proximal,large-volume,or leaks that persist despite urinary diversion,require open repair.Vesicoureteral reflux is common following transplantation.Patients with recurrent pyelonephritis despite antimicrobial prophylaxis require surgical treatment.Deflux injection may be considered in recipients with low-grade disease.Grade IV and V reflux are best managed with open reconstruction.

Epstein-Barr virus-positive post-transplant lymphoproliferative disordepresenting as hematochezia and enterobrosis in renal transplant recipients in China: A report of two cases

BACKGROUND Post-transplant lymphoproliferative disorder(PTLD) is a rare severe complication after renal transplantation, with an incidence of approximately 0.3%-2.0% in patients undergoing renal transplantation. The clinical manifestations of PTLD are often nonspecific, leading to tremendous challenges in the clinical diagnosis and treatment of PTLD.CASE SUMMARY We report two Epstein-Barr virus(EBV)-positive PTLD cases whose main clinical manifestations were digestive tract symptoms. Both of them admitted to our hospital because of extranodal infiltration symptoms and we did not suspect of PTLD until the pathology confirmation. Luckily, they responded well to the treatment of rituximab. We also discuss the virological monitoring, clinical characteristics, diagnosis, and treatment of PTLD.CONCLUSION PTLD is a deceptive disease and difficult to diagnose. Once patients are confirmed with PTLD, immune suppressant dosage should be immediately reduced and rituximab should be used as first-line therapy.

ABO incompatibility in renal transplantation

ABO blood group incompatibility(ABO-I)was historically considered an absolute contraindication to kidney transplantation due to the significant risk of acute antibody-mediated rejection and early graft loss.Nevertheless,the urge to minimize the gap between the candidates’number on the waitlist for kidney transplants and the available kidney donors encourage investigation into finding ways to use organs from ABO-I kidney donors,especially in the era of using more potent immunosuppression therapies.This review aims to discuss a general overview of ABO-I kidney transplantation and the different protocols adopted by some transplant centers to meaningfully overcome this barrier.

Renal transplant recipient seizure practical management

Seizures are not uncommon in renal transplant patients.The common aetiologies are metabolic disturbance associated with renal failure,immunosuppression and associated complications and infections.Their management can be challenging because of altered pharmacokinetics of antiepileptic drugs(AEDs)and their removal by dialysis.A practical approach to the management of seizure in renal transplant patients is discussed.This review highlights the guidelines for use of various AEDs in renal transplants.

Treatment of Donor-derived Carbapenem-resistant Klebsiella pneumoniae Infection after Renal Transplantation with Tigecycline and Extended-infusion Meropenem

Objective Donor-derived carbapenem-resistant Klebsiella pneumoniae(CRKP)infection has recently emerged as a critical early complication after renal transplantation.Although CRKP is usually sensitive to tigecycline,monotherapy with this drug is often less than effective.We investigated the efficacy of a combined regimen of tigecycline with high-dose,extended-infusion meropenem in the treatment of donor-derived CRKP infection after kidney transplantation.Methods From Jan.2016 to Dec.2017,a total of 12 CRKP isolates were detected from cultures of the organ preservation solution used for soaking the donor kidneys at our institute.Probable or possible donor-derived infection(DDI)was identified in 8 transplant recipients.Clinical data were retrospectively analyzed.Results Klebsiella pneumoniae carbapenemase-2(KPC-2)-producing CRKP was reported to be positive in organ preservation solution cultures at 3.5±0.9 days after transplantation,leading to surgical site(n=3),urinary tract(n=4),and/or bloodstream(n=2)infections in 8 recipients.The drug susceptibility tests showed that CRKP was sensitive to tigecycline,but resistant to meropenem.In 7 patients who received tigecycline combined with high-dose extended-infusion meropenem,DDIs were successfully cured.The length of hospital stay was 31(18–129)days,and the serum creatinine at discharge was 105.8±16.7µmol/L.The one remaining patient who received tigecycline combined with intravenous-drip meropenem died of septic shock.A median follow-up of 43 months(33–55)showed no recurrence of new CRKP infection in the 7 surviving recipients.Conclusion It was suggested that a prompt and appropriate combination therapy using tigecycline with high-dose extended-infusion meropenem is effective in treating donor-derived KPC-2-producing CRKP infection after renal transplantation.

Results of cataract surgery in renal transplantation and hemodialysis patients

AIMTo compare the effect of cataract surgery in renal transplantation and hemodialysis patients.METHODSWe evaluated 51 eyes of 31 renal transplantation patients, 41 eyes of 29 hemodialysis patients and 45 eyes of 32 normal control patients who received phacoemulsification and intraocular lens (IOL) implantation from January, 2000 to August, 2014 in the Beijing Friendship Hospital. Each individual underwent a blood routine and a kidney function examination. Routine ophthalmologic examination included best-corrected visual acuity (BCVA), a slit-lamp examination to detect cataract type, determination of intraocular pressure, a corneal endothelial count, and fundus examination. All patients received phacoemulsification and an IOL implantation.RESULTSFor the types of cataract in the three groups, transplantation group was significantly different from normal control group (P=0.04), the most kind is posterior subcapsular cataract (PSC) in transplantation group 33 (64.7%), hemodialysis group had no significantly difference from normal control group (P=0.43), and the difference between transplantation group and hemodialysis group also had significantly difference (P=0.02). For postoperative BCVA in the three groups, transplantation group had significantly difference from normal control group (P=0.03), hemodialysis group was significantly different from normal control group (P=0.00), and the difference between transplantation group and hemodialysis group also had significantly difference (P=0.00). The multiple linear regression equation is Y=0.007 hemoglobin (Hb)-0.000233 serum creatinine (Cr), R2=0.898. Postoperative fundus examination showed that hemorrhage, exudation, and macular degeneration were greater in the hemodialysis group.CONCLUSIONThis study showed that the PSC was more in the renal transplantation patients. BCVA was better and fundus lesions were less frequent in the renal transplantation group than in the hemodialysis group after cataract surgery. The multiple linear regression was showed that the Hb was positively correlated with postoperative BCVA, while Cr was negatively correlated with postoperative BCVA. These results may act as indicators in predicting visual acuity for the renal transplantation and hemodialysis patients.

Hepatitis B in renal transplant patients

Hepatitis B virus(HBV) poses a significant challenge for both dialysis patients and kidney transplant recipients despite its decreasing rates, especially in developed countries. The best preventive method is vaccination. Patients with chronic renal disease should ideally be vaccinated prior to dialysis, otherwise, reinforced vaccination practices and close antibody titer monitoring should be applied while on dialysis. HBV infected dialysis patients who are renal transplant candidates must be thoroughly examined by HBV-DNA, and liver enzyme testing and by liver biopsy. When needed, one must consider treating patients with tenofovir or entecavir rather than lamivudine. Depending on the cirrhosis stage, dialysis patients are eligible transplant recipients for either a combined kidney-liver procedure in the case of decompensated cirrhosis or a lone kidney transplantation since even compensated cirrhosis after sustained viral responders is no longer considered an absolute contraindication. Nucleoside analogues have led to improved transplantation outcomes with both long-term patient and graft survival rates nearing those of HBs Ag(-) recipients. Moreover, in the cases of immunized HBs Ag(-) potential recipients with concurrent prophylaxis, we are enabled today to safely use renal grafts from both HBs Ag(+) and HBs Ag(-)/antiHBc(+) donors. In so doing, we avoid unnecessary organ discarding. Universal prophylaxis with entecavir is recommended in HBV kidney recipients and should start perioperatively. One of the most important issues in HBV(+) kidney transplantation is the duration of antiviral prophylaxis. In the absence of robust data, it seems that prophylactic treatment may be discontinued in selected stable, low-risk recipients during maintenance immunosuppression and should be reintroduced when the immune status is altered. All immunosuppressive agents in kidney transplantation can be used in HBV(+) recipients. Immunosuppression is intimately associated with increased viral replication; thus it is important to minimize the total immunosuppression burden long term.

Dynamic regulation of anti-oxidation following donation repairing after circulatory determined death renal transplantation with prolonged non-heart-beating time

Donation after circulatory-determined death(DCD)is an important part of renal transplantation.Therefore,DCD renal transplantation animal model should be established to study the mechanism of organ injury.Here,we established a stable DCD rat renal transplantation model and investigated the dynamic regulation of graft self-repairing and antioxidant capacities with different non-heart-beating times(NHBTs).Male Sprague-Dawley rats were randomly divided into four groups with the NHBT of the donors from 0 to 15,30,and 45 minutes.Recipients in long NHBT groups had a significantly lower survival rate and poorer graft function than those in short NHBT groups.Grafts from the 15-minute and 30-minute NHBT groups showed light and severe injury respectively at an early stage after transplantation and recovered within 7 days after transplantation,whereas the self-repairing of the grafts in the 45-minute NHBT group was delayed.The expressions of proliferating cell nuclear antigen(PCNA)and von Willebrand factor(vWF)were dependent on NHBT.The expression of antioxidant proteins paralleled graft recovery.In conclusion,the recipients can up-regulate antioxidant capacity to enhance graft self-repairing in DCD renal transplantation.Prolonged NHBT can delay the self-repairing and antioxidation of grafts.

Idiopathic acute superior mesenteric venous thrombosis after renal transplantation: A case report

BACKGROUND Acute superior mesenteric venous thrombosis(MVT)is a rare condition associated with a high mortality rate.The treatment strategy for MVT is clinically challenging due to its insidious onset and rapid development,especially when accompanied by kidney transplantation.CASE SUMMARY Here we present a rare case of acute MVT developed 3 years after renal transplantation.A 49-year-old patient was admitted with acute abdominal pain and diagnosed as MVT with intestinal necrosis.An emergency exploratory laparotomy was performed to remove the infarcted segment of the bowel.Immediate systemic anticoagulation was also initiated.During the treatment,the patient experienced bleeding,anastomotic leakage,and sepsis.However,after aggressive treatment was administered,all thrombi were completely resolved,and the patient recovered with his renal graft function unimpaired.CONCLUSION The present case suggests that accurate diagnosis and timely surgical treatment are important to improve the survival rate of MVT patients.Bleeding with anastomotic fistula needs to be treated with caution because of grafts.Also,previously published cases of mesenteric thrombosis after renal transplantation were reviewed.

Coronavirus disease 2019 and renal transplantation

Ever since the severe acute respiratory syndrome virus causing coronavirus disease 2019(COVID-19)struck the world,global health strategies have changed significantly.According to the Centers for Disease Control and Prevention,kidney transplant recipients are stratified as being high risk of developing fatal illness from COVID-19 infection.Kidney transplant is the gold-standard treatment for end-stage kidney disease subjects.During the pandemic,significant concerns have emerged regarding continuation of kidney transplant surgeries and management of kidney transplant recipients post-transplant.The added risk of immunosuppression in this cohort was and remains a theoretical concern,posing a potential risk of transplantation rather than benefit.This comprehensive review aims to cover most of the faced challenges in kidney transplantation in different stages of the pandemic.In addition,it will elucidate the epidemiology,nature,course of the disease,surgical consideration in donors and recipients as well as role of immunosuppression and management of COVID-19 infected kidney transplant recipients during these extraordinary circumstances.

RELATIONSHIP BETWEEN CYTOMEGALOVIRUS INFECTION AND THE PRODUCTION OF ANTICARDIOLIPIN ANTIBODY IN RENAL TRANSPLANT RECIPIENTS

Objective To investigate the relationship between cytomegalovirus (CMV) infection and the production of anticardiolipin antibody (ACA) in renal transplant recipients.Methods Polymerase chain reaction (PCR) was used qualitatively for detection of CMV DNA in 146 renal transplant recipients.Meanwhile,enzyme linked immunosorbent assay (ELISA) was used for detection of ACA IgG in blood serum samples from these recipients and 32 healthy individuals. Results The ACA positive rate was 17.1% among the 146 renal transplant recipients,and that of the control group was 6.3%.There was no significant difference.However,the ACA positive rate of the renal transplant recipients infected with CMV was 31.2%.It was clearly higher than that of those with no infection of CMV and that of the control group ( P <0.005). Conclusion The production of ACA was closely related to CMV infection.It might be one of the factors of chronic angiopathy of the transplanted kidney due to CMV infection.