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.

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.

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.

Impact of Vascular Variations on Living Donor Kidney Transplantation

Background: Kidney transplantation is the best treatment for end-stage chronic kidney disease. However, its realization is confronted by several difficulties among which are anatomical variations. Objective: The objective of our work was to describe the impact of renal pedicle variations on the operative procedure as well as the complications. Method: We conducted a retrospective study on living kidney donors and their recipients in the period from 2012 to 2017. Several variables were studied, in particular socio-demographic, operative and progression. Results: We identified 49 living donors whose mean age was 37.59 years with a male-to-female ratio of 3.9 and 45 ± 10.75 years in the recipients. The prevalence of renal vascular abnormalities was higher with a proportion of 46.94% in recipients. The left kidney was most frequently removed (75.51%) and then kept mainly in HTK (95.92%). These vascular anomalies were associated with a longer operating time but this difference was not statistically significant (p = 0.5804). They had no effect on hot and cold ischemia times (p = 0.9838, p = 0.8389). Complications were observed in 11 patients, all recipients, i.e. 11.22%, and were not related to the presence of vascular abnormalities (p = 0.086). We observed that 4.08% of deaths were all recipients. Conclusion: It seems that kidney transplantation with multiple renal arteries and/or veins does not significantly lengthen the operating time and does not promote the onset of complications.

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.

Right versus left fully robotic live donor nephrectomy and open kidney transplantation:Does the laterality of the donor kidney really matter?

Objective Robotic-assisted live donor nephrectomy(LDN)is being gradually adopted across transplant centers.The left donor kidney is preferred over right due to anatomical factors and ease of procurement.We aimed to study donor and recipient outcomes after robotic procurement and subsequent open implantation of right and left kidneys.Methods All fully robotic LDNs and their corresponding open kidney transplants performed at our center between February 2016 and December 2021 were retrospectively analyzed.Results Out of 196 robotic LDN(49[right]vs.147[left]),10(5.1%)donors had intra-operative events(6.1%[right]vs.4.8%[left],p=0.71).None of the LDN required conversion to open surgery.The operative times were comparable for the two groups.Nausea(13.3%)was the most common post-operative complication.There was no mortality in either LDN group.Herein,we report our outcomes on 156 recipients(39 right and 117 left allografts)excluding robotic implants,exports,and pediatric recipients.There were no significant differences between right and left kidney recipients with respect to 1-year post-transplant patient survival(100.0%vs.98.1%,p=0.45)or graft survival(93.9%vs.97.1%,p=0.11),or delayed graft function(7.7%vs.5.1%,p=0.55).Conclusion Non-hand-assisted robotic live donor nephrectomies can be safely performed with excellent outcomes.Right LDN was not associated with higher incidence of complications compared to left LDN.Open implantation of robotically procured right renal allografts was not associated with higher risk of recipient complications.

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.

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.

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.

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.

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.

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.

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.

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.

Surgical Complications of Kidney Transplantation in a Resource Limited Country: Retrospective Study of the First Five Years

Background: Kidney transplantation is the most efficient treatment for renal failure but may be ruined by complications. Objective: To report the surgical complications of renal transplantation and the therapeutic means applied. Method: It was a retrospective study including 42 files of kidney transplantation in Côte d’Ivoire. We report 11 cases of surgical complications of the recipient’s intervention during the first five years. Results: The mean age was 42.64 years (±15.04). In 90.9% of the cases, there was a comorbidity factor. Lymphocele and stenosis of the uretero vesical anastomosis were the most frequent complications. One death was observed. Conclusion: Kidney transplantation is an effective way of managing chronic renal failure. Postoperative complications are polymorphic and unpredictable.

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.

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.

Transplantation Therapy of Cats with Chronic Renal Failure

Abstract Dialysis therapy is not a radical cure of chronie renal failure in eats. while renal transplantation is the cure method, Renal transplantalion requires rigorous examinatinn of donor and receptor, and the procedure is strictly sterile. The main points of renal Iransplantalion are： renal artery and vein sutured to abdominal aorta and psterior vena tara, respectively; ureter sutured to bladder; minimizing the time of thermal isehemia. Cats should be given immunosuppressant betore lhe operation, and the drug should be administered throughout the life. Various indicators shouhl be mnnitored regularly to prevent the occurrence of immunologieal rejcetion.

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.