Future of non-invasive graft evaluation:A systematic review of proteomics in kidney transplantation

BACKGROUND Despite the developments in the field of kidney transplantation,the already existing diagnostic techniques for patient monitoring are considered insufficient.Protein biomarkers that can be derived from modern approaches of proteomic analysis of liquid biopsies(serum,urine)represent a promising innovation in the monitoring of kidney transplant recipients.AIM To investigate the diagnostic utility of protein biomarkers derived from proteomics approaches in renal allograft assessment.METHODS A systematic review was conducted in accordance with PRISMA guidelines,based on research results from the PubMed and Scopus databases.The primary focus was on evaluating the role of biomarkers in the non-invasive diagnosis of transplant-related com-plications.Eligibility criteria included protein biomarkers and urine and blood samples,while exclusion criteria were language other than English and the use of low resolution and sensitivity methods.The selected research articles,were categorized based on the biological sample,condition and methodology and the significantly and reproducibly differentiated proteins were manually selected and extracted.Functional and network analysis of the selected proteins was performed.RESULTS In 17 included studies,58 proteins were studied,with the cytokine CXCL10 being the most investigated.Biological pathways related to immune response and fibrosis have shown to be enriched.Applications of biomarkers for the assessment of renal damage as well as the prediction of short-term and long-term function of the graft were reported.Overall,all studies have shown satisfactory diagnostic accuracy of proteins alone or in combination with conventional methods,as far as renal graft assessment is concerned.CONCLUSION Our review suggests that protein biomarkers,evaluated in specific biological fluids,can make a significant contribution to the timely,valid and non-invasive assessment of kidney graft.

Endothelial dysfunction in the kidney transplant population:Current evidence and management strategies

The endothelium modulates vascular homeostasis owing to a variety of vasoconstrictors and vasodilators.Endothelial dysfunction(ED),characterized by impaired vasodilation,inflammation,and thrombosis,triggers future cardiovascular(CV)diseases.Chronic kidney disease,a state of chronic inflammation caused by oxidative stress,metabolic abnormalities,infection,and uremic toxins damages the endothelium.ED is also associated with a decline in estimated glomerular filtration rate.After kidney transplantation,endothelial functions undergo immediate but partial restoration,promising graft longevity and enhanced CV health.However,the anticipated CV outcomes do not happen due to various transplant-related and unrelated risk factors for ED,culminating in poor CV health and graft survival.ED in kidney transplant recipients is an underrecognized and poorly studied entity.CV diseases are the leading cause of death among kidney transplant candidates with functioning grafts.ED contributes to the pathogenesis of many of the CV diseases.Various biomarkers and vasoreactivity tests are available to study endothelial functions.With an increasing number of transplants happening every year,and improved graft rejection rates due to the availability of effective immunosuppressants,the focus has now shifted to endothelial protection for the prevention,early recognition,and treatment of CV diseases.

Expanding role of antibodies in kidney transplantation

The role of antibodies in kidney transplant(KT)has evolved significantly over the past few decades.This role of antibodies in KT is multifaceted,encompassing both the challenges they pose in terms of antibody-mediated rejection(AMR)and the opportunities for improving transplant outcomes through better detection,prevention,and treatment strategies.As our understanding of the immunological mechanisms continues to evolve,so too will the approaches to managing and harnessing the power of antibodies in KT,ultimately leading to improved patient and graft survival.This narrative review explores the multifaceted roles of antibodies in KT,including their involvement in rejection mechanisms,advancements in desensitization protocols,AMR treatments,and their potential role in monitoring and improving graft survival.

Comparative study of living donor kidney transplants:Right vs left

BACKGROUND Transplant teams often hesitate to use the right kidney(RK)in living donor(LD)transplants due to the complexities of anastomosing the short,thin-walled right renal veins,which can potentially lead to graft loss or graft dysfunction.Nevertheless,circumstances may arise where selecting the RK over the left kidney(LK)is unavoidable.Consequently,it is crucial to thoroughly examine the implications of such a choice on the overall transplant outcome.AIM To compare transplant outcomes between recipients of RK and LK while examining the factors that influence these outcomes.METHODS We retrospectively analyzed data from adult patients who received LD kidney transplants involving meticulous patient selection and surgical techniques at our center from January 2020 to December 2023.We included all kidney donors who were over 18,fit to donate,and had undergone diethylenetriamine pentaacetic acid split function and/or computed tomography based volumetry.The variables examined comprised donor and recipient demographics,and outcome measures included technical graft loss(TGL),delayed or slow graft function(SGF),and post-transplant serum creatinine(SC)trends.We used a logistic regression model to assess the likelihood of adverse outcomes considering the donor kidney side.RESULTS Of the 250 transplants performed during the period,56(22%)were RKs.The recipient demographics and transplant factors were comparable for the right and LKs,except that the donor warm and cold ischemia time were shorter for RKs.TGL and SGF each occurred in 2%(n=1)of RKs and 0.5%(n=1)of LKs,the difference being insignificant.These complications,however,were not related to the venous anastomosis.One RK(2%)developed delayed graft function after 48 hours,which was attributable to postoperative hypoxia rather than the surgical technique.The post-transplant SC trend and mean SC at the last follow-up were similar across both kidney sides.CONCLUSION The donor kidney side has little impact on post-transplant adverse events and graft function in LD transplants,provided that careful patient selection and precise surgical techniques are employed.

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

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

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

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

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.

Clinical use of donor-derived cell-free DNA in kidney transplantation

Traditional monitoring of kidney transplant recipients for allograft dysfunction caused by rejection involves serial checks of serum creatinine with biopsy of the renal allograft if dysfunction is suspected.This approach is labor-intensive,invasive and costly.In addition,because this approach relies on a rise in serum creatinine above historical baselines,injury to the allograft can be extensive before this rise occurs.In an effort to address this,donor-derived cell-free DNA(dd-cf DNA)is being used with increasing frequency in the clinical setting as a means of diagnosing a rejection of the renal allograft early in the course.This can poten-tially allow for early intervention to minimize not only injury,but the intensity of antirejection therapy needed and the avoidance of side effects.Here,we will review the available methodology for the determination and quantification of dd-cf DNA,the data supporting its use in clinical practice and the limitations of this technology.

Kidney transplantation outcomes: Is it possible to improve when good results are falling down?

Famure et al describe that close to 50%of their patients needed early or very early hospital readmissions after their kidney transplantation.As they taught us the variables related to those outcomes,we describe eight teaching capsules that may go beyond what they describe in their article.First two capsules talk about the ideal donors and recipients we should choose for avoiding the risk of an early readmission.The third and fourth capsules tell us about the reality of cadaveric donors and recipients with comorbidities,and the way transplant physicians should choose them to maximize survival.Fifth capsule shows that any mistake can result in an early readmission,and thus,in poorer outcomes.Sixth capsule talks about economic losses of early readmissions,cost-effectiveness of tran-splantation,and how to improve outcomes and reduce costs by managing a risky patient-portfolio.Seventh capsule argues about knowing your risk behavior to better manage your portfolio;and Eighth capsule about the importance of the center experience in transplanting complex patients.We finish with some lessons of the importance of the transplantation process and the collaboration with other disciplines in order to prevent the conditions that lead to early readmissions.

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

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

Impact of Medicaid expansion on kidney transplantation in the State Oklahoma

BACKGROUND There is no data evaluating the impact of Medicaid expansion on kidney tran-splants(KT)in Oklahoma.AIM To investigate the impact of Medicaid expansion on KT patients in Oklahoma.METHODS The UNOS database was utilized to evaluate data pertaining to adult KT reci-pients in Oklahoma in the pre-and post-Medicaid eras.Bivariate analysis,Kaplan Meier analysis was used to estimate,and cox proportional models were utilized.RESULTS There were 2758 pre-and 141 recipients in the post-Medicaid expansion era.Post-expansion patients were more often non-United States citizens(2.3%vs 5.7%),American Indian,Alaskan,or Pacific Islander(7.8%vs 9.2%),Hispanic(7.4%vs 12.8%),or Asian(2.5%vs 8.5%)(P<0.0001).Waitlist time was shorter in the post-expansion era(410 vs 253 d)(P=0.0011).Living donor rates,pre-emptive transplants,re-do transplants,delayed graft function rates,kidney donor profile index values,panel reactive antibodies levels,and insurance types were similar.Patients with public insurance were more frail.Despite increased early(<6 months)rejection rates,1-year patient and graft survival were similar.In Cox proportional hazards model,male sex,American Indian,Alaskan or Pacific Islander race,public insurance,and frailty category were independent risk factors for death at 1 year.Medicaid expansion was not associated with graft failure or patient survival(adjusted hazard ratio:1.07;95%CI:0.26-4.41).CONCLUSION Medicaid expansion in Oklahoma is associated with increased KT access for non-White/non-Black and non-United States citizen patients with shorter wait times.1-year graft and patient survival rates were similar before and after expansion.Medicaid expansion itself was not independently associated with graft or patient survival outcomes.Ongoing research is necessary to determine the long-term effects of Medicaid expansion.

Clinical course and outcome of adult patients with primary focal segmental glomerulosclerosis with kidney function loss on presentation

BACKGROUND Kidney function loss or renal insufficiency indicated by elevated creatinine levels and/or an estimated glomerular filtration rate(eGFR)<60 mL/minute/1.73 m²at presentation in patients with primary focal segmental glomerulosclerosis(FSGS)is commonly seen as a poor prognostic marker for kidney survival.However,a pre>vious study from our center suggested this may be due to hemodynamic factors.AIM To observe the clinical and biochemical parameters,treatment response,kidney survival,and overall outcomes of adult patients with primary FSGS presenting with kidney function insufficiency.METHODS This retrospective observational study was conducted at the Department of Nephrology,Sindh Institute of Urology and Transplantation,Karachi,Pakistan,from January 1995 to December 2017.During this period,401 biopsy-proven primary FSGS patients were identified,of which 98(24.4%)presented with kidney function loss or renal insufficiency defined as eGFR<60 mL/minute/1.73 m²at presentation and were studied in detail.RESULTS Among the 98 patients with renal function loss on presentation,the mean age was 30.9 years±13.6 years with a male-to-female ratio of 2.5:1.The mean serum creatinine level was 2.2 mg/dL±1.3 mg/dL and mean eGFR 37.1 mL/minute/1.73 m2±12.8 mL/minute/1.73 m2.The mean 24-hour urinary protein excretion was 5.9 g/day±4.0 g/day,and the mean serum albumin was 2.1 g/dL±1.0 g/dL(median:1.5 g/dL).The mean systolic blood pressure(BP)was 132.7 mmHg±19.8 mmHg,and the mean diastolic BP was 87.4 mmHg±12.7 mmHg.Steroid treatment was given to 81(82.6%)of 98 patients for an average duration of 19.9 weeks±14.4 weeks,with a mean total steroid dose of 4.4 g±1.5 g.Treatment response showed that 20(24.6%)patients achieved complete remission,9(11.1%)achieved partial remission,and 52(64.1%)did not respond.The baseline eGFR was significantly lower in the non-responsive group(P=0.006).The distribution of FSGS variants was also significantly different among steroid-responsive and non-responsive groups(P=0.012).CONCLUSION Renal function loss in FSGS patients at presentation does not necessarily indicate irreversible kidney function loss and a significant number of patients respond to appropriate treatment of the underlying disease.

Interferon-free regimens in patients with hepatitis C infection and renal dysfunction or kidney transplantation

Treatment of patients with chronic kidney disease(CKD) and chronic hepatitis C(CHC) differs from that used in the general CHC population mostly when glomerular filtration rate(GFR) is below 30 m L/min, as sofosbuvir, the backbone of several current regimens, is officially contraindicated. Given that ribavirin free regimens are preferable in CKD, elbasvir/grazoprevir is offered in CHC patients with genotype 1 or 4 and ombitasvir/paritaprevir and dasabuvir in genotype 1b for 12 wk. Although regimens containing peginterferon with or without ribavirin are officially recommended for patients with CKD and genotype 2, 3, 5, 6, such regimens are rarely used because of their low efficacy and the poor safety and tolerance profile. In this setting, especially in the presence of advanced liver disease, sofosbuvirbased regimens are often used, despite sofosbuvir contraindication. It seems to have good overall safety with only 6% or 3.4% of CKD patients to discontinue therapy or develop serious adverse events without drug discontinuation. In addition, sustained virological response(SVR) rates with sofosbuvir based regimens in CKD patients appear to be comparable with SVR rates in patients with normal renal function. Treatment recommendations for kidney transplant recipients are the same with those for patients with CHC, taking into consideration potential drug-drug interactions and baseline GFR before treatment initiation. This review summarizes recent data on the current managementof CHC in CKD patients highlighting their strengths and weaknesses and determining their usefulness in clinical practice.

Sexual and reproductive function in end-stage renal disease and effect of kidney transplantation

Advanced chronic kidney disease is associated with impaired spermatogenesis and testicular damage. Semen analysis typically shows a decreased volume of ejaculate, oligo-or complete azoospermia, and a low percentage of motile sperm. Erectile dysfunction （ED） is also common in patients with chronic renal failure （CRF） and is observed in excess of 50% of these patients. There have been ongoing improvements in survival and quality of life after renal transplantation. One of the most impressive aspects of successful renal transplantation in the young people is the ability of the male patient to father a child. In this article we first review pathophysiology of reproductive failure in end-stage renal disease （ESRD）, then ED in ESRD and its management are discussed, finally sexual function in renal transplant patients and management of ED in these patients are reviewed.

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

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

Perioperative risk factors associated with delayed graft function following deceased donor kidney transplantation:A retrospective,single center study

BACKGROUND There is an abundant need to increase the availability of deceased donor kidney transplantation(DDKT)to address the high incidence of kidney failure.Challenges exist in the utilization of higher risk donor organs into what appears to be increasingly complex recipients;thus the identification of modifiable risk factors associated with poor outcomes is paramount.AIM To identify risk factors associated with delayed graft function(DGF).METHODS Consecutive adults undergoing DDKT between January 2016 and July 2017 were identified with a study population of 294 patients.The primary outcome was the occurrence of DGF.RESULTS The incidence of DGF was 27%.Under logistic regression,eight independent risk factors for DGF were identified including recipient body mass index≥30 kg/m^(2),baseline mean arterial pressure<110 mmHg,intraoperative phenylephrine administration,cold storage time≥16 h,donation after cardiac death,donor history of coronary artery disease,donor terminal creatinine≥1.9 mg/dL,and a hypothermic machine perfusion(HMP)pump resistance≥0.23 mmHg/mL/min.CONCLUSION We delineate the association between DGF and recipient characteristics of preinduction mean arterial pressure below 110 mmHg,metabolic syndrome,donorspecific risk factors,HMP pump parameters,and intraoperative use of phenylephrine.

Complement activation and long-term graft function in ABO-incompatible kidney transplantation

BACKGROUND ABO-incompatible and ABO-compatible kidney transplantation are equivalent in terms of short-term graft and patient survival. This is thought to be the result of ABO-incompatible graft accommodation, which occurs when anti-blood group antibodies re-occur after transplantation but somehow do not yield their detrimental effect. The underlying mechanism is unclear, but one of the hypotheses is that this is the result of complement inhibition. Since virtually all ABO-incompatible graft biopsies are C4d positive, this complement inhibition must occur somewhere in the complement cascade after the formation of C4d has already taken place, but where exactly is unclear. It is also unclear whether complement inhibition is complete. Incomplete accommodation could explain why recent studies have shown that long-term graft function in ABOincompatible transplantation is somewhat inferior to ABO-compatible kidney transplantation.AIM To unravel the relationship between pre-transplant anti-ABO antibodies,complement activation, and long-term graft function.METHODS We included all 27 ABO-incompatible transplantations that were performed between 2008 and 2013 at the Academic Medical Center Amsterdam and the University Medical Center Groningen. For each ABO-incompatible transplantation, we included four ABO-compatible controls matched by age, sex,and transplantation date.RESULTS Graft and patient survival were not significantly different. The slope of kidney function during five-year follow-up was also not significantly different, but ABOincompatible recipients did have a lower kidney function at three months(creatinine clearance 58 vs 69 mL/min, P = 0.02, Modification of Diet in Renal Disease 46 vs 52 mL/min/1.73 m^2, P = 0.08), due to a high rate of early rejection(33% vs 15%, P = 0.03), mostly T-cell mediated. Pre-transplant anti-ABO Ig G titers were positively correlated with C5b-9 staining, which itself was positively correlated with the occurrence of T-cell mediated rejection. This may be the result of concurrent C5a formation, which could function as a costimulatory signal for T-cell activation.CONCLUSION Co-stimulation of T-cell activation by ongoing complement activation by antiABO antibodies may be responsible for an impaired long-term graft function in ABO-incompatible kidney transplantation.

An Observational Study on the Clinical and Nutritional Factors Determining the Kidney Function at One Year after Transplantation

Objective: The aim of the present study was to investigate the clinical and nutritional factors influencing the renal function of the transplanted kidney during a one-year follow-up period after transplantation. Patients: The present prospective observational study included 52 patients who underwent kidney transplantation at Jichi Medical University Hospital from 2014 to 2016. Results: The serum creatinine (sCr) concentration at one month after transplantation was closely related to the concentration at 12 months. The recipients were divided into two groups based on the sCr concentration at one month after transplantation. Recipients with a sCr concentration greater than or equal to the median were classified into Group H, while those with concentrations that were less than the median were classified into Group L. A stepwise multiple regression analysis demonstrated that the salt intake in male recipients was an independent predictor of the renal function at 12 months (β = 0.663, p β = 0.618, p < 0.01). Moreover, in female recipients, the BMI and serum uric acid values in Group H were significantly higher than those in Group L. The BMI values of the female recipients in Group H were significantly higher than those in Group L at all times during the follow-up period (p < 0.01). Conclusion: The daily salt intake was independently associated with the renal function at one year after kidney transplantation in male recipients. In female recipients, the BMI was independently associated with the sCr concentration during the one-year follow-up period.

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

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

Application and management of continuous glucose monitoring in diabetic kidney disease

Diabetic kidney disease(DKD)is a common complication of diabetes mellitus that contributes to the risk of end-stage kidney disease(ESKD).Wide glycemic var-iations,such as hypoglycemia and hyperglycemia,are broadly found in diabetic patients with DKD and especially ESKD,as a result of impaired renal metabolism.It is essential to monitor glycemia for effective management of DKD.Hemoglobin A1c(HbA1c)has long been considered as the gold standard for monitoring glycemia for>3 months.However,assessment of HbA1c has some bias as it is susceptible to factors such as anemia and liver or kidney dysfunction.Continuous glucose monitoring(CGM)has provided new insights on glycemic assessment and management.CGM directly measures glucose level in interstitial fluid,reports real-time or retrospective glucose concentration,and provides multiple glycemic metrics.It avoids the pitfalls of HbA1c in some contexts,and may serve as a precise alternative to estimation of mean glucose and glycemic variability.Emerging studies have demonstrated the merits of CGM for precise monitoring,which allows fine-tuning of glycemic management in diabetic patients.Therefore,CGM technology has the potential for better glycemic monitoring in DKD patients.More research is needed to explore its application and management in different stages of DKD,including hemodialysis,peritoneal dialysis and kidney transplantation.