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.

Optimizing growth in pediatric renal transplant recipients: An update

Growth retardation is a significant complication observed in pediatric renal transplant recipients,originating from a multifactorial etiology.Factors contributing to growth impairment encompass pre-transplant conditions such as primary kidney disease,malnutrition,quality of care,growth deficits at the time of transplantation,dialysis adequacy,and the use of recombinant human growth hormone.Additionally,elements related to the renal transplant itself,such as living donors,corticosteroid usage,and graft functioning,further compound the challenge.Although renal transplantation is the preferred renal replacement therapy,its impact on achieving final height and normal growth in children remains uncertain.The consequences of growth delay extend beyond the physi-ological realm,negatively influencing the quality of life and social conditions of pediatric renal transplant recipients,and ultimately affecting their educational and employment outcomes.Despite advancements in graft survival rates,growth retardation remains a formidable clinical concern among children undergoing renal transplantation.Major risk factors for delayed final adult height include young age at transplantation,pre-existing short stature,and the use of specific immunosuppressive drugs,particularly steroids.Effective management of growth retardation necessitates early intervention,commencing even before transplantation.Strategies involving the administration of recombinant growth hormone both pre-and post-transplant,along with protocols aimed at minimizing steroid usage,are important for achieving catch-up growth.This review provides a comprehensive outline of the multifaceted nature of growth retardation in pediatric renal transplant recipients,emphasizing the importance of early and targeted interventions to mitigate its impact on the long-term well-being of these children from birth to adolescence.INTRODUCTION Children with chronic kidney disease(CKD)endure frequent hospitalizations and ongoing treatment,which significantly affect their quality of life.One of the most noticeable effects of CKD in children is poor growth,with stunted height being a common sign of chronic malnutrition.Growth assessment involves regularly measuring weight and height/length and comparing these against z-score charts,along with other anthropometric indicators like head circumference and mid-upper arm circumference.Data from the North American Pediatric Renal Trials and Collaborative Studies(NAPRTCS)registry shows that over 35%of children enrolled had stunted growth at the time of admission,with growth impairment being more severe in younger children(58%in those aged under 1 year,compared to 22%in those aged over 12 years).Additionally,the same data revealed that growth impairment worsens as the severity of the disease increases.Although recent advances in science have enabled better outcomes for children with CKD,in resource-limited settings,numerous children are still deprived of achieving optimal growth owing to the disease and its related factors.Stunting is a key indicator of chronic growth impairment in children.A study by Wong et al[1]in the United States Renal Data System found that each SD decrease in height among children with stage V CKD is linked to a 14%increase in the risk of death[1].Similarly,research by Furth et al[2]using data from the NAPRTCS indicated that children with a height standard deviation score(SDS)of-2.5 face a relative hazard of death of 2.07.Stunting also correlates with increased hospitalizations.A study in the United States followed 1112 pediatric patients with end-stage renal disease from 1990 to 1995.It showed that children with severe or moderate growth failure had higher hospitalization rates compared to those with normal growth.Specifically,the relative risk for hospitalization was 1.14(95%CI:1.1-1.2)for those with moderate growth failure and 1.24(95%CI:1.2-1.3)for those with severe growth failure,even after adjusting for age,sex,race,cause,and duration of end-stage renal disease,and treatment type[2](dialysis or transplant).The growth of a child significantly affects his/her psychological and overall well-being as an adult.Short children are often embarrassed by peers,and it has been observed that height influences employment status,with unemployment being more prevalent among stunted individuals.Further,marital opportunities can be fewer among stunted individuals[3].Hence,all measures to achieve adequate growth should be attempted in children with CKD,regardless of whether they undergo transplantation.

Peliosis hepatis complicated by portal hypertension following renal transplantation

Peliosis hepatis(PH)is a vascular lesion of the liver that mimics a hepatic tumor.PH is often associated with underlying conditions,such as chronic infection and tumor malignancies,or with the use of anabolic steroids,immunosuppressive drugs,and oral contraceptives.Most patients with PH are asymptomatic,but some present with abdominal distension and pain.In some cases,PH may induce intraperitoneal hemorrhage and portal hypertension.This study analyzed a 46-year-old male who received a transplanted kidney nine years prior and had undergone long-term immunosuppressive therapy following the renal transplantation.The patient experienced progressive abdominal distention and pain in the six months prior to this study.Initially,imaging studies revealed multiple liver tumor-like abnormalities,which were determined to be PH by pathological analysis.Because the hepatic lesions were progressively enlarged,the patient suffered from complications related to portal hypertension,such as intense ascites and esophageal varices bleeding.Although the patient was scheduled to undergo liver transplantation,he suffered hepatic failure and died prior to availability of a donor organ.

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.

EXPRESSION OF ICAM-1 AND LFA-1 MOLECULES IN RELATION TO RENAL ALLOGRAFT REJECTION IN RATS

Objective.The purpose of this study was to assess the renal graft expression of ICAM 1(intercellular adhesion molecule 1) and LFA 1(lymphocyte function associated antigen 1)molecule with relation to graft rejection. Methods.Rat kidney transplantation was performed according to the procedure of Kamada with some modification.Experimental rats were divided into 5 groups.The survival time of recipient rats and function of grafts after renal transplantation were observed.The sections of renal graft were stained for monoclonal antibody ICAM 1 and LFA 1, and then quantification of ICAM 1 and LFA 1 expression was accomplished by computer image analysis. Results.ICAM 1 and LFA 1 increased significantly in the renal allograft rejection group as compared with the non rejection groups(P<0 05). Conclusion.Both biopsy of renal graft and monitoring of ICAM 1 and LFA 1 are useful tools in diagnosing and treating acute rejection.

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.

Treatment of advanced rectal cancer after renal transplantation

Renal transplantation is a standard procedure for endstage renal disease today. Due to immunosuppressive drugs and increasing survival time after renal transplantation, patients with transplanted kidneys carry an increased risk of developing malignant tumors. In this case report, 3 patients with advanced rectal cancer after renal transplantation for renal failure were treated with anterior resection or abdominoperineal resection plus total mesorectal excision, followed by adjuvant chemotherapy. One patient eventually died of metastasized cancer 31 mo after therapy, although his organ grafts functioned well until his death. The other 2 patients were well during the 8 and 21 mo followup periods after rectal resection. We therefore strongly argue that patients with advanced rectal cancer should receive standard oncology treatment, including operation and adjuvant treatment after renal transplantation. Colorectal cancer screening in such patients appears justified.

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.

Asymptomatic hyperuricemia following renal transplantation

in the genesis and progression of kidney disease, and a few studies are beginning to show a possible benefcial effect of urate-lowering therapy. Whether this holds true for renal allograft recipients is not clear. In this short review evidence from epidemiological as well as intervention studies is summarized and discussed, with some practical considerations presented at the end.

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.

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.

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.

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.

Depressive symptoms and associated factors among renal-transplant recipients in China

Aim:This study aimed to explore depressive symptoms and associated factors among renal-transplant(RT)recipients in China.Methods:This study included 287 RT recipients.Data were collected from August to November 2014 by utilizing demographic forms,namely,the Self-rating Depression Scale and the Multidimensional Scale of Perceived Social Support.Descriptive statistics,Student's t test,Chi-square test,ANOVA,and multiple linear regression were used for data analysis.Results:More than half of the recipients presented depressive symptoms.All recipients in the four transplant period groups(≤5 yr,5e10 yr,10e15 yr,and>15 yr)reported greater depressive symptoms than the Norm.No significant difference was observed in the depressive symptoms in the four transplant period groups.Multiple linear regression indicated that depressive symptoms were significantly associated with employment status,economic burden,inhabitation area,and social support.Conclusion:Depression is common among RT recipients in China.Employment status,economic burden,inhabitation area,and social support are the main factors affecting depression among RT recipients.Follow-up clinics should prescribe the evaluation of depression as a routine examination for RT patients.Moreover,depressed recipients must be provided with individualized care by collecting information on the depressive symptoms,employment status,economic burden,inhabitation area,and perceived social support of recipients.

Cost of two different therapies for end-stage renal disease in northwest China

Currently,the growing number of end-stage renal disease patients in developing countries consumes a greater proportion of healthcare budget,and increasing attention is being focused on the cost-effectiveness of the procedure.We aimed to assess the cost-effectiveness of living-related renal transplantation (RTx) as compared with that for hemodialysis (HD) and identify medical factors associated with charges for RTx in northwestern China.This study was a retrospective analysis of 372 patients on regular HD and 122 living-related kidney transplant recipients on regular follow-up for at least 3 years in northwestern China.All data on charges included HD procedure,RTx procedure,the cost for donor operation,immunosuppression,and follow-up medicare.The average annual cost to all patients on HD and kidney recipients during the first 3 years after RTx was $14482/$31027,$13502/$11038,and $13382/$10243,respectively.The three variables were found to be significant in predicting increased costs for RTx:diltiazem administration,acute rejection and infection complications.We concluded that from the second year on,RTx in China was more effective and less costly than dialysis treatment,although recipients without diltiazem administration and with acute rejection or infection proved costlier during the first year after transplantation.

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.

Investigation on the Perceptions of Living Donors regarding Spousal Renal Donor Transplantation

In Japan the average waiting time to receive a kidney from brain-dead patients or those in cardiac death is about 14 years. Therefore there is an increasing reliance of kidneys from living donor. Spouses are an important source of living-donor kidney grafts because, despite poor HLA matching, the graft-survival rate is similar to that of parental-donor kidneys. This study investigated the perceptions of living donors regarding spousal renal donor transplantation. We interviewed 8 donors about their feelings after transplantation using structured interviews. Many donors were not anxious and did not consider donation dangerous. However, in the case that the rejection occurred, as a result, transplantation was unsuccessful, the donor felt vain, and regretted that she was donor. On the other hand, total nephrectomy is often performed as a treatment for small size （4 cm or less） renal tumors and many of these nephrectomized kidneys could be successfully transplanted after surgical restoration with satisfactory results. Because of the lack of necessary evidence, it is currently not allowed in Japan. We estimated the 5-year recurrence rate of cancer after restored kidney transplantation would be less than 6%.We also asked donors the rights and wrongs for using the restored kidneys.

Therapeutic effectiveness of pediatric renal transplantation in 63 cases

Objective： To explore the characteristic of operation, intra-operation treatment and the application of immunosuppressant in pediatric renal transplantation in order to improve therapeutic effectiveness. Methods： From March 1986 to October 2006, the clinical data of 63 children who underwent renal transplantation in our hospital were retrospectively analyzed. Results： The 1-, 3-, 5-, 10-year graft survival rates were 98.4%, 90.5%, 88.9% and 68.3%, respectively. And the corresponding patient survival rates were 100%, 95.2%, 92.1%, 71.4%. The body weight increased 4 to 12 kg and the body height grew up 2 to 6 cm during the first year post-transplantation. The main complications in the first year post-transplantation were hypertension （26/63, 41.3%）, crinosity （14/63, 22.2%）, drug-induced hepatic injury（11/63, 17.5%）, gingival hyperplasia （10/63, 15.8%）, pulmonary infection（9/63, 14.3%）, bone marrow suppression（5/63, 7.9%）, herpes （4/63, 6.3%） and diabetes （3/63, 4.8%）. Conclusion： Renal transplantation is a preferred method for the treatment of children in end-stage renal disease （ESRD）. Good tissue matching, proper operative time and pattern, peri-operactive care were essential to success, as well as appropriate immuno-suppressant strategy and good compliance.

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.