Cryptococcosis in kidney transplant recipients:Current understanding and practices

Cryptococcosis is the third most commonly occurring invasive fungal disease in solid organ transplant recipients(SOT).It is caused by encapsulated yeast,Cryptococcus species,predominantly Cryptococcus neoformans and Cryptococcus gattii.Though kidney transplant recipients are at the lowest risk of cryptococcosis when compared to other solid organ transplant recipients such as lung,liver or heart,still this opportunistic infection causes significant morbidity and mortality in this subset of patients.Mortality rates with cryptococcosis range from 10%-25%,while it can be as high as 50%in SOT recipients with central nervous system involvement.The main aim of diagnosis is to find out if there is any involvement of the central nervous system in disseminated disease or whether there is only localized pulmonary involvement as it has implications for both prognostication and treatment.Detection of cryptococcal antigen(CrAg)in cerebrospinal fluid or plasma is a highly recommended test as it is more sensitive and specific than India ink and fungal cultures.The CrAg lateral flow assay is the single point of care test that can rapidly detect cryptococcal polysaccharide capsule.Treatment of cryptococcosis is challenging in kidney transplant recipients.Apart from the reduction or optimization of immunosuppression,lipid formulations of amphotericin B are preferred as induction antifungal agents.Consolidation and maintenance are done with fluconazole;carefully monitoring its interactions with calcineurin inhibitors.This review further discusses in depth the evolving developments in the epidemiology,pathogenesis,diagnostic assays,and management approach of cryptococcosis in kidney transplant recipients.

Awareness of Cytomegalovirus Infection among a Population of Nigerian Kidney Transplant Recipients

Background: Cytomegalovirus (CMV) is the most important infection in kidney transplant recipients and has significant impact on long term recipient and graft survival. Objective: The aim of this study is to assess the level of awareness of CMV infection among a population of kidney transplant recipients in Lagos, Nigeria. Subjects and Methods: The assessment of the level of awareness of CMV infection among kidney transplant recipients attending post-transplant follow-up clinics in Lagos, Nigeria was done by means of a structured pre-tested self-administered questionnaire from October 2004 to July 2005. Results: A total of 40 kidney transplant recipients were studied. Thirty-two recipients were males and eight were females with M:F ratio of 4:1. The mean age of the recipients was 39 ± 11.6 years old. The recipients’ post-transplant duration ranged from 2 to 80 months (Mean 17.6 ± 18.6 months). Only four (10%) of kidney transplant recipients studied had ever heard of CMV infection and only one recipient (2.5%) was aware that CMV infection could affect a transplanted kidney, and that CMV infection could be transmitted from the donor kidney graft to the recipient. One recipient (2.5%) was aware that blood transfusion could be a mode of transmission of CMV infection. None of the recipients was aware that CMV infection could be sexually transmitted. All the four recipients who were aware of CMV infection obtained the information from their doctors. Conclusion: Despite its significant impact on kidney transplant recipient and graft survival, the level of awareness of CMV infection and its relevance to kidney transplantation was very low among kidney transplant recipients. Transplant units in the study environment should include information and education about CMV infection and its impact on the transplant recipient and graft survival in their counseling programme for transplant recipients.

Clinical study of sirolimus-associated interstitial pneumonitis in kidney transplant recipients

Objective To studt the sirolimus ( SRL) - associated interstitial pneumonitis,which is a severe side effect of sirolimus therapy. Methods In 7 renal grafts treated with SRL,interstitial pneumonitis ( 8 times) was diagnosed. One patient suffered a relapse after

Impact of bisphosphonate treatment on bone mineral density after kidney transplant

BACKGROUND Mineral bone disease is associated with chronic kidney disease and persists after kidney transplantation.Immunosuppressive treatment contributes to the patho-genesis of this disease.Bisphosphonate treatments have shown positive but inde-finite results.AIM To evaluate the effectiveness and safety of bisphosphonate treatment on post kidney transplantation bone mineral density(BMD).METHODS We included kidney transplant recipients(KTRs)whose BMD was measured after the operation but before the initiation of treatment and their BMD was measured at least one year later.We also evaluated the BMD of KTRs using two valid mea-surements after transplantation who received no treatment(control group).RESULTS Out of 254 KTRs,62(39 men)were included in the study.Bisphosphonates were initiated in 35 KTRs in total(20 men),1.1±2.4 years after operation and for a period of 3.9±2.3 years while 27(19 men)received no treatment.BMD improved significantly in KTRs who received bisphosphonate treatments(from-2.29±1.07 to-1.66±1.09,P<0.0001).The control group showed a non-significant decrease in BMD after 4.2±1.4 years of follow-up after surgery.Kidney function was not affected by bisphosphonate treatment.In KTRs with established osteoporosis,active treatment had a similar and significant effect on those with osteopenia or normal bone mass.CONCLUSION In this retrospective study of KTRs receiving bisphosphonate treatment,we showed that active treatment is effective in preventing bone loss irrespective of baseline BMD.

Translation and cross-cultural adaptation of the Kidney Transplant Questionnaire 25 to Greek

BACKGROUND Kidney transplantation leads to continuous improvement in the survival rates of kidney transplant recipients(KTRs)and has been established as the treatment of choice for patients with end-stage kidney disease.Health-related quality of life(HRQoL)has become an important outcome measure.It is highly important to develop reliable methods to evaluate HRQoL with disease-specific questionnaires.AIM To translate the disease-specific instrument Kidney Transplant Questionnaire 25(KTQ-25)to the Greek language and perform a cross-cultural adaptation.METHODS The translation and adaptation of the original English version of the KTQ-25 to the Greek language were performed based on the International Quality of Life RESULTS Eighty-four KTRs(59 males;mean age 53.5±10.7 years;mean estimated glomerular filtration rate 47.7±15.1 mL/min/1.73 m2;mean transplant vintage 100.5±83.2 months)completed the Greek version of the KTQ-25 and the 36-item Short-Form Health Survey,and the results were used to evaluate the reliability of the Greek KTQ-25.The Cronbach alpha coefficients for all the KTQ-25 dimensions were satisfactory(physical symptoms=0.639,fatigue=0.856,uncertainty/fear=0.661,appearance=0.593,emotions=0.718,total score=0.708).The statistically significant correlation coefficients among the KTQ-25 dimensions ranged from 0.226 to 0.644.The correlation coeffi-cients of the KTQ-25 dimensions with the SF-36 physical component summary(PCS)ranged from 0.196 to 0.550;the correlation coefficients of the KTQ-25 with the SF-36 mental component summary(MCS)ranged from 0.260 to 0.655;and the correlation coefficients of the KTQ-25 with the total scores with the SF-36 PCS and MCS were 0.455 and 0.613,respectively.CONCLUSION According to the findings,the Greek version of the KTQ-25 is valid and reliable for administration among kidney transplant patients in Greece.

Efficacy and Safety of Different Bisphosphonates for Bone Loss Prevention in Kidney Transplant Recipients： A Network Meta-Analysis of Randomized Controlled Trials

Background： Mineral and bone disorder is one of the severe complications in kidney transplant recipients （KTRs）. Previous studies showed that bisphosphonates had favorable effects on bone mineral density （BMD）. We sought to compare different bisphosphonate regimens and rank their strategies. Methods： We searched PubMed, Embase, and the Cochrane Central Register of Controlled Trials （CENTRAL） up to April 01, 2017,for randomized controlled trials （RCTs） comparing bisphosphonate treatments in adult KTRs. The primary outcome was BMD change. We executed the tool recommended by the Cochrane Collaboration to evaluate the risk of bias. We performed pairwise meta-analyses using random effects models and network meta-analysis （NMA） using Bayesian models and assessed the quality of evidence. Results： A total of 21 RCTs （1332 participants） comparing 6 bisphosphonate regimens were included. All bisphosphonates showed a significantly increased percentage change in BMD at the lumbar spine compared to calcium except clodronate. Pamidronate with calcium and Vitamin D analogs showed improved BMD in comparison to clodronate with calcium （mean difference [MD], 9.84; 95% credibility interval [CrI], 1.06-19.70）. The combination of calcium and Vitamin D analogs had a significantly lower influence than adding either pamidronate or alendronate （MD, 6.34; 95% CrI, 2.59-11.01 and MD, 6.16; 95% CrI, 0.54-13.24, respectively）. In temas of percentage BMD change at the femoral neck, both pamidronate and ibandronate combined with calcium demonstrated a remarkable gain compared with calcium （MD, 7.02; 95% CrI, 0.30-13.29 and MD, 7.30; 95% CrI, 0.32-14.22, respectively）. The combination of ibandronate with calcium displayed a significant increase in absolute BMD compared to any other treatments and was ranked best. Conclusions： Our NMA suggested that new-generation bisphosphonates such as ibandronate were more favorable in KTRs to improve BMD. However, the conclusion should be treated with caution due to indirect comparisons.

Relationship of Transforming Growth Factor-β1 and Arginase-1 Levels with Long-term Survival after Kidney Transplantation

In this study, we compared the serum levels of transforming growth factor-β1 （TGF-β1）, interleukin-10 （IL-10）, and arginase-1 in long-term survival kidney transplant recipients （LTSKTRs） with those in short-term survival kidney transplant recipients （STSKTRs）. We then evaluated the relationship between these levels and graft function. Blood samples were collected from 50 adult LTSKTRs and 20 STSKTRs （graft survival approximately 1-3 years post-transplantation）. All patients had stable kidney function. The samples were collected at our institution during the patients＇ follow-up examinations between March 2017 and September 2017. The plasma levels of TGF-β1, IL- 10, and arginase- 1 were analyzed using enzyme-linked immunosorbent assays （ELISA）. The levels of TGF-β1 and arginase-1 were significantly higher in the LTSKTRs than in the STSKTRs. The time elapsed since transplantation was positively correlated with the levels of TGF-β1 and arginase-1 in the LTSKTRs. The estimated glomerular filtration rate was positively correlated with the TGF-β1 level, and the serum creatinine level was negatively correlated with the TGF-β1 level. Higher serum levels of TGF-β1 and arginase-1 were found in LTSKTRs than in STSKTRs, and we found that TGF-β1 was positively correlated with long-term graft survival and function. Additionally, TGF-β1 and arginase-1 levels were positively correlated with the time elapsed since transplantation. On the basis of these findings, TGF-β1 and arginase- 1 may play important roles in determining long-term graft survival. Thus, we propose that TGF-β1 and arginase-1 may potentially be used as predictive markers for evaluating long-term graft survival.

Supportive care in transplantation: A patient-centered care model to better support kidney transplant candidates and recipients

Kidney transplantation(KT),although the best treatment option for eligible patients,entails maintaining and adhering to a life-long treatment regimen of medications,lifestyle changes,self-care,and appointments.Many patients experience uncertain outcome trajectories increasing their vulnerability and symptom burden and generating complex care needs.Even when transplants are successful,for some patients the adjustment to life post-transplant can be challenging and psychological difficulties,economic challenges and social isola-tion have been reported.About 50%of patients lose their transplant within 10 years and must return to dialysis or pursue another transplant or conservative care.This paper documents the complicated journey patients undertake before and after KT and outlines some initiatives aimed at improving patient-centered care in transplantation.A more cohesive approach to care that borrows its philosophical approach from the established field of supportive oncology may improve patient experiences and outcomes.We propose the"supportive care in transplantation"care model to operationalize a patient-centered approach in transplantation.This model can build on other ongoing initiatives of other scholars and researchers and can help advance patient-centered care through the entire care continuum of kidney transplant recipients and candidates.Multi-dimensionality,multi-disciplinarity and evidence-based approaches are proposed as other key tenets of this care model.We conclude by proposing the potential advantages of this approach to patients and healthcare systems.Core Tip:Kidney transplant recipients and candidates face several uncertainties in their care journey and have several expressed unmet healthcare needs.We recommend a structured and comprehensive approach to transplant care across the entire continuum of a transplant patient’s journey similar to what has been developed in the field of oncology.The supportive care in transplantation model can operationalize patient-centered care and build on the efforts of other researchers in the field.We postulate that such a model would significantly improve care delivery and patients’experiences and outcomes and potentially decrease healthcare utilization and cost.INTRODUCTION Patients with kidney failure benefit from(KT)[1,2],and experience improved survival rates when compared with dialysis[3-6].KT studies,using validated instruments,have also consistently demonstrated that kidney transplant recipients(KTRs)experience better health-related quality of life and several improvements in other disease-specific domains when compared with dialysis[7].In countries where dialysis is out of reach for many,the diagnosis of kidney failure would be futile without KT[8].Thus,increasing KT has been a priority for the nephrology and transplant communities.This priority has been reflected in recent global trends:Of the 79 countries where data were available,the International Society of Nephrology’s Global Kidney Atlas reported that the prevalence of KTRs in 2023 was 279 per million population which represented an increase of 9.4%from the data published four years prior[8].Despite this growth,KT can be a challenging journey for many patients and it is sometimes regarded as a‘cure’,which does not conform with the reality that many patients experience[9-13].KTRs must maintain a life-long treatment regimen of medications,lifestyle changes,self-care and medical appointments[14-17].As poignantly stated by a young female transplant recipient,“I thought everything would change once I got my kidney.I thought I would be healthy again”but after experiencing multiple side effects of immunosuppressive medications and graft loss,she stated,“I am just a different kind of patient now”[18].Indeed,a significant proportion of patients experience graft failure and return to dialysis;it is estimated that over 50%return to dialysis within 10 years of KT[19-23].Patients are often not prepared for this outcome and report several psychosocial and physical ramifications of graft failure[24,25].Overall,high symptom burden,adverse effects of immunosuppressants,risk of graft rejection or failure and mortality,contribute to complex needs,vulnerability and uncertainties for patients,increasing their care needs and treatment burden[26-30].In this paper,we highlight the complex journey that KTRs and candidates undertake that can generate varied outcome trajectories and complex healthcare needs.We highlight the need for a comprehensive patient-centered approach to care and conclude with a proposal for a“supportive care in transplantation”care model.

Frailty in kidney transplant candidates and recipients: pathogenesis and intervention strategies

With the rapid aging of the global population posing a serious problem,frailty,a non-specific state that reflects physiological senescence rather than aging in time,has become more widely addressed by researchers in various medical fields.A high prevalence of frailty is found among kidney transplant(KT)candidates and recipients.Therefore,their frailty has become a research hotspot in the field of transplantation.However,current studies mainly focus on the cross-sectional survey of the incidence of frailty among KT candidates and recipients and the relationship between frailty and transplantation.Research on the pathogenesis and intervention is scattered,and relevant review literature is scarce.Exploring the pathogenesis of frailty in KT candidates and recipients and determining effective intervention measures may reduce waiting list mortality and improve the long-term quality of life of KT recipients.Therefore,this review explains the pathogenesis and intervention measures for frailty in KT candidates and recipients to provide a reference for the formulation of effective intervention strategies.