Chronic Allograft Nephropathy Research Articles

Egyptian pediatric kidney transplantation: highlights on post-transplant follow-up and management of complications by the Egyptian Pediatric Clinical Practice Guidelines Committee (EPG) Nephrology Group

BackgroundPediatric kidney transplantation is unique when compared to adults. They need optimum post-transplant care to achieve longer graft and patient survival. Infections, rejection, recurrence, malignancy, bone problems, hypertension, and surgical complications are the most important challenges that require prevention, early detection, and management. Chronic allograft nephropathy needs different approaches based on its related causes, allograft pathology, graft function, and availability of re-transplantation.Aim/objectivesThis national adapted guideline aims to frame evidence-based post-transplant recommendations adopted or adapted from EB source guidelines to optimize post-transplant patient care.MethodsOur guideline is evidence based adapted from four national and international source guidelines with permissions [KDIGO 2020, RA/BTS 2022–2018, EAU 2018] that were appraised with AGREE II instrument tool. We followed the “adapted ADAPTE” CPG formal adaptation methodology that consists of 3 phases and 24 steps and tools. Virtual monthly meetings all through the year 2023 were activated for reviewing and validation of final adaptation of evidence-based guideline draft, considering all comments of external reviewers. This guideline was registered in the practice guideline registration for transparency (PREPARE), number: PREPARE-2023CN364.ResultsRecommendation statements in guidelines stand for results in articles. Discussion of important recommendations and the rationale behind selection of adopted statements and tailoring of others to suit our local facilities, expertise, and renal native disease profile was presented in the text with reasons and references.ConclusionThe provided guidelines aim to improve graft and patient outcome through prevention and early management of complications and suggest research areas lacking validated research recommendations.

Kynurenine Pathway after Kidney Transplantation: Friend or Foe?

Kidney transplantation significantly improves the survival of patients with end-stage kidney disease (ESKD) compared to other forms of kidney replacement therapy. However, kidney transplant recipients' outcomes are not fully satisfactory due to increased risk of cardiovascular diseases, infections, and malignancies. Immune-related complications remain the biggest challenge in the management of kidney graft recipients. Despite the broad spectrum of immunosuppressive agents available and more detailed methods used to monitor their effectiveness, chronic allograft nephropathy remains the most common cause of kidney graft rejection. The kynurenine (KYN) pathway is the main route of tryptophan (Trp) degradation, resulting in the production of a plethora of substances with ambiguous properties. Conversion of Trp to KYN by the enzyme indoleamine 2,3-dioxygenase (IDO) is the rate-limiting step determining the formation of the next agents from the KYN pathway. IDO activity, as well as the production of subsequent metabolites of the pathway, is highly dependent on the balance between pro- and anti-inflammatory conditions. Moreover, KYN pathway products themselves possess immunomodulating properties, e.g., modify the activity of IDO and control other immune-related processes. KYN metabolites were widely studied in neurological disorders but recently gained the attention of researchers in the context of immune-mediated diseases. Evidence that this route of Trp degradation may represent a peripheral tolerogenic pathway with significant implications for transplantation further fueled this interest. Our review aimed to present recent knowledge about the role of the KYN pathway in the pathogenesis, diagnosis, monitoring, and treatment of kidney transplant recipients' complications.

Complications associated with kidney transplantation, causes of graft failure and mortality following kidney transplantation in patients with systemic lupus erythematosus: a meta-analysis

IntroductionDespite improvement in the management of systemic lupus erythematosus (SLE) during the past two decades, 10–22% of patients with lupus nephritis (LN) will progress to end-stage renal disease (ESRD). Kidney transplantation is among the possible treatment for patients with SLE progressing to ESRD. However, the issue with kidney transplantation in patients with SLE is controversial. In this analysis, we aimed to compare the complications associated with kidney transplantation, causes of graft failure and causes of mortality following kidney transplantation in patients with SLE with ESRD.MethodsThe sources of data included http://www.ClinicalTrials.gov, EMBASE, MEDLINE, Google Scholar, Web of Science and the Cochrane database. Revman software version 5.4 was used for the data analysis whereby risk ratio (RR) with 95% confidence intervals (CI) were used to represent data following analysis. In addition, the Q statistic test and the I2 statistic test were used to assess heterogeneity. A random effect statistical model was used and a subgroup outcome with a P-value less than 0.05 was considered statistically significant.ResultsA total number of 149,330 participants enrolled between the years 1968 and 2018 were included in this analysis with 7534 participants with SLE.Results of this analysis showed that mortality (RR 1.07, 95% CI 0.89–1.29; P = 0.45), graft failure (RR 1.22, 95% CI 0.99–1.55; P = 0.07) and delayed graft function (RR 1.01, 95% CI 0.44–2.34; P = 0.98) were not significantly higher in renal transplant patients with SLE versus a control group. When the causes of graft failure were analysed in renal transplant patients with SLE versus without SLE, acute graft rejection (RR 1.20, 95% CI 0.98–1.47; P = 0.07), chronic graft rejection (RR 0.76, 95% CI 0.57–1.03; P = 0.08), graft thrombosis (RR 1.47, 95% CI 0.83–2.63; P = 0.19), recurrence of disease (RR 3.08, 95% CI 1.00–9.47; P = 0.05) and chronic allograft nephropathy (RR 1.08, 95% CI 0.60–1.95; P = 0.80) were also not significantly higher in patients with SLE. On the basis of the analysis, mortality from any cardiac cause (RR 0.82, 95% CI 0.67–1.01; P = 0.06), sepsis (RR 1.19, 95% CI 0.93–1.53; P = 0.17), malignancy (RR 0.79, 95% CI 0.51–1.24; P = 0.31) and cerebrovascular attack (RR 0.76, 95% CI 0.44–1.30; P = 0.31) were not significantly different in kidney transplantation patients with versus without SLE.ConclusionsComplications associated with kidney transplantation including mortality, graft failure and delayed graft function were not significantly higher in patients with SLE when compared with a control group. The causes of graft failure and mortality after kidney transplantation were also comparable in both groups. Therefore, kidney transplantation represents a promising treatment in patients with SLE with ESRD.

Comparison of Adverse Events Following Immunosuppressant Administration for Pediatric Patients With Renal Transplants Categorized by Two-Year Age Increments Using the U.S. Food and Drug Administration Adverse Event Reporting System.

Background Immunosuppressants are frequently administered to prevent transplant rejection in patients with renal transplants but cause various adverse events. The incidence of each adverse event may differ between pediatric and adult patients with renal transplants. Because the development of organs and bodies in pediatric patients varies greatly annually, the incidence of each adverse event following immunosuppressant administration may vary by age. Consequently, the age-specific incidence of each adverse event in pediatric patients represents invaluable information for clinical settings. To clarify trends in the occurrence of adverse events by age, a large sample size for each age is required. However, it is difficult to conduct clinical trials in pediatric patients with renal transplants with a large sample size for each age. One method to address this difficulty is to use a database. Objectives This study aimed to investigate the trends in the occurrence of each adverse event following immunosuppressant administration in pediatric patients with renal transplants, categorized by two-year age increments. Methods We extracted data on pediatric patients aged 0-17 years who received immunosuppressants after renal transplant between January 2004 and March 2024 from the U.S. Food and Drug Administration Adverse Event Reporting System. Because adverse events were greatly affected by age, the patients were divided into groups by two-year age increments. We analyzed the relationship between the groups and the reporting proportion of each adverse event by using the reporting regression coefficient (RRC) from univariate regression analysis and the adjusted RRC (aRRC), which controlled for differences in patient background. Results Renal tubular necrosis, renal impairment, chronic allograft nephropathy, and headache were the adverse events that required more attention with increasing age because RRC and aRRC were significantly > 0. By contrast, Epstein-Barr virus infection was the adverse event that required attention, especially in younger pediatric patients, because RRC and aRRC were significantly < 0. Additionally, there were various trends among other adverse events, including those that required careful monitoring across all ages 0-17 years. Conclusions This study demonstrated that the types of adverse events requiring attention in pediatric patients with renal transplants differ by age. These findings can help enhance treatment and care in pediatric clinical settings.

Use of Donor-derived Cell-free DNA to Inform Tapering of Immunosuppression Therapy in Kidney Transplant Recipients: An Observational Study.

Immunosuppression therapy (IST) is required for allograft survival but can cause significant adverse effects. Donor-derived cell-free DNA (dd-cfDNA) is a validated noninvasive biomarker for active rejection in kidney transplant (KTx). Evidence supporting dd-cfDNA testing use in IST management is limited. In this single-center observational study, dd-cfDNA testing was performed in 21 KTx patients considered good candidates for mycophenolic acid (MPA) reduction. Patients with dd-cfDNA <1% at the first visit (enrollment) had their MPA dosage reduced; those with dd-cfDNA ≥1% had their MPA dosage maintained. Patients were monitored with dd-cfDNA for 6 additional visits. Of 21 patients enrolled in the study, 17 were considered low risk for rejection by dd-cfDNA and underwent MPA reduction; 4 patients were considered high risk for rejection by dd-cfDNA and had their initial MPA dosage maintained. Of the 4 patients considered high risk for rejection by dd-cfDNA, 1 experienced chronic allograft nephropathy and graft loss, and another received an indication biopsy that showed no evidence of rejection. Of the 17 patients considered low risk for rejection by dd-cfDNA, none experienced allograft rejection. dd-cfDNA was used for surveillance in a 6-mo period following MPA reduction; no untoward results were noted. This proof-of-concept study reports the use of dd-cfDNA to directly inform IST management in a cohort of KTx who were candidates for IST reduction.

The causes of death-censored graft loss among kidney transplant recipients

Objective: This study presents the causes of death-censored graft loss among kidney transplant recipients. Materials and Methods: Medical records of the patients, who had undergone kidney transplantation at a tertiary center between November 2010 and December 2018, were retrospectively reviewed. Death-censored graft loss was described as an irreversible graft failure signified by return to long-term dialysis (or re-transplantation). Inclusion criteria were: patients who had undergone kidney transplantation, and subsequently lost their first graft, and a follow-up of more than one year after kidney transplantation. Results: Of 269 kidney transplant recipients, 33 recipients with a mean age of 33.54 ± 15.37 years (17 male and 16 female) were included in the study. The rate of death-censored graft loss was 12.26%. Of graft failures, 3.03% occurred in the hyperacute phase, 18.18% in the acute phase, and 78.78% in the chronic phase. Chronic allograft nephropathy was the leading cause of graft failure (48.48%). Other causes were medical problems (18.18), immunological problems (18.18%) and surgical complications (15.15%). Conclusion: Identification of the true causes of graft failure described under the heading chronic allograft nephropathy is noteworthy. Comprehensive biochemical, physiological, pathological, immunological, and genetic research should be implemented to remove the obstacles in kidney transplantations.

ПОЧЕЧНО-КЛЕТОЧНЫЙ РАК ТРАНСПЛАНТАТА ПОЧКИ: ОПИСАНИЕ КЛИНИЧЕСКОГО СЛУЧАЯ И КРАТКИЙ ОБЗОР ЛИТЕРАТУРЫ

A retrospective analysis of a patient with renal cell carcinoma (RCC) in renal allografts is presented, providing a comprehensive overview of the patient's medical history, the findings from various examinations, and the surgical interventions. The patient had end-stage renal disease due to nephrosclerosis following a kidney allotransplantation in 2008 and subsequently developed chronic allograft nephropathy. Upon examination, a tumor was discovered in the lower pole of the transplanted kidney. As a result of the end-stage renal transplant failure development, the patient underwent radical surgical treatment using advanced image-guided surgical techniques. This case is a compelling example of the critical importance of regular, thorough screenings for patients undergoing immunosuppressive therapy to identify any potential neoplastic processes promptly. Keywords: Kidney transplantation, kidney carcinoma, renal allograft embolization, transplant nephrectomy.

Viral specific T cell therapy in kidney transplant recipients - A single-center experience.

Viral infections such as adenovirus (ADV), BK virus (BKV), and cytomegalovirus (CMV) after kidney transplantation negatively impact outcomes in transplant recipients despite advancements in screening and antiviral therapy. We describe our experience of using the virus-specific T cell therapy (VSTs) in kidney transplant recipients (KTR) at our transplant center. This is a retrospective, single center review of KTR with ADV, BKV and CMV infections between June 2021 and December 2022. These patients received third party VSTs as part of the management of infections. The immunosuppression, details of infection and outcome data were obtained from electronic medical records. Two cases of ADV infection resolved after one infusion of VSTs. The response rate of BKV and CMV infection was not as robust with close to 50% reduction in median viral load after VSTs. Out of 23 patients, two patients developed chronic allograft nephropathy from membranoproliferative glomerulonephritis and acute rejection. Patients that are resistant to antivirals or who have worsening viremia despite conventional management may benefit from VSTs therapy to treat underlying viral infection. Additional studies are needed to ascertain efficacy and short- and long-term risks secondary to VSTs.

The Use of Diffusion Tensor Imaging in the Identification of Acute Rejection and Chronic Allograft Nephropathy After Renal Transplantation.

Identifying the cause of renal allograft dysfunction is important for the clinical management of kidney transplant recipients. To evaluate the diagnostic efficiency of diffusion tensor imaging (DTI) for identifying allografts with acute rejection (AR) and chronic allograft nephropathy (CAN). Prospective. Seventy-seven renal transplant patients (aged 42.5 ± 9.5 years), including 29 patients with well-functioning stable allografts (Control group), 25 patients diagnosed with acute rejection (AR group), and 23 patients diagnosed with chronic allograft nephropathy (CAN group). 1.5 T/T2-weighted imaging and DTI. The serum creatinine, proteinuria, pathologic results, and fractional anisotropy (FA) values were obtained and compared among the three groups. One-way analysis of variance; correlation analysis; independent-sample t-test; intraclass correlation coefficients and receiver operating characteristic curves. Statistical significance was set to a P-value <0.05. The AR and CAN groups presented with significantly elevated serum creatinine as compared with the Control group (191.8 ± 181.0 and 163.1 ± 115.8 μmol/L vs. 82.3 ± 20.9 μmol/L). FA decreased in AR group (cortical/medullary: 0.13 ± 0.02/0.31 ± 0.07) and CAN group (cortical/medullary: 0.11 ± 0.02/0.27 ± 0.06), compared with the Control group (cortical/medullary: 0.15 ± 0.02/0.35 ± 0.05). Cortical FA in the AR group was higher than in the CAN group. The area under the curve (AUC) for identifying AR from normal allografts was 0.756 and 0.744 by cortical FA and medullary FA, respectively. The AUC of cortical FA and medullary FA for differentiating CAN from normal allografts was 0.907 and 0.830, respectively. The AUC of cortical FA and medullary FA for distinguishing AR and CAN from normal allografts was 0.828 and 0.785, respectively. Cortical FA was able to distinguish between AR and CAN with an AUC of 0.728. DTI was able to detect patients with dysfunctional allografts. Cortical FA can further distinguish between AR and CAN. 2 TECHNICAL EFFICACY: Stage 2.

Application of Real-Time Sound Touch Elastography for Evaluating Chronic Kidney Disease of Transplanted Kidneys

If chronic allograft nephropathy can be detected early and treated, the long-term survival rate of the transplanted kidney may be effectively improved. To compare the application value of real-time sound touch elastography (STE), strain elastography, and color Doppler flow imaging in evaluating chronic kidney disease of transplanted kidneys. A total of 101 patients with renal transplantation were divided into a normal group (serum creatinine <134 mol/L, 58 patients) and a chronic allograft nephropathy group after renal transplantation over 6 months (serum creatinine >134 mol/L, 43 patients). The maximum elastic modulus (Emax) was determined, and receiver operator characteristics were used to compare the diagnostic efficacy of STE ultrasound. Emean, Emax, B/A (the strain rate of the internal oblique muscle tissue/the strain rate of the central renal cortex) of cortical standard strain ratio in strain elastography, and resistance index (RI) between normal and chronic allograft nephropathy groups have statistical significance (P < .05). Emax is superior to B/A and arcuate artery RI in the chronic cortex in the diagnosis of renal dysfunction, and the area under the receiver operator characteristics curve is 0.88. The estimated glomerular filtration rate was negatively correlated with renal cortex Emax, B/A, and arcuate artery RI, among which Emax was the strongest (r=- 0.713, P < .001). The renal cortical Emax cut-off was 30.95 kPa, the sensitivity was 92%, the specificity was 88%, and the accuracy was 88%. The STE technique to evaluate chronic renal dysfunction after renal transplantation is more sensitive than traditional strain-type elastography and hemodynamic parameters, with renal function decline, renal cortex Emax, renal cortical B/A, and arcuate artery RI gradually increased, and renal cortex Emax was particularly obvious.

Prospective quantitative study: Doppler ultrasound in the evaluation of chronic renal allograft disease and correlation with histopathological finding.

Renal allograft biopsy is the gold standard for diagnosing chronic allograft nephropathy, but noninvasive methods are needed to avoid unnecessary biopsies. Doppler ultrasonography, particularly the resistive index (RI), correlates with renal allograft dysfunction. This study aims to assess the relationship between renal sonographic parameters and biochemical parameters in diagnosing graft interstitial fibrosis. The study evaluated 60 renal allograft recipients for sonographic renal morphological features and Doppler indices. The estimated glomerular filtration rate (eGFR) was calculated, and cortical fibrosis after the biopsy was determined using the Banff score. Continuous variables like mean and SD were calculated, and categorical variables were reported using frequencies and proportions. Associations were examined using independent sample t-tests, χ 2tests, and multivariate regression analysis. The mean eGFR was 75.23±25.45ml/min/1.73m2. A significant correlation of eGFR with RI (r=0.341, P=0.008) was seen. A significant difference in mean RI (F=10.167; df=2,57; P<0.001) was seen among the histological grades of fibrosis. Among the histological grades of fibrosis, significant differences in RI among mild and moderate (S.E. 0.033, P=0.043), mild and severe (S.E. 0.026, P=0.001) as well as moderate and severe (S.E. 0.036, P=0.029) was seen. Doppler was able to noninvasively predict allograft fibrosis and could be used as a complementary imaging tool during the follow-up of renal allograft patients. Future research is needed to improve evidence, diagnostic criteria, guidelines, and long-term impact.

Live Related Kidney Transplantation: Experience of 360 Patients in a Tertiary Care Hospital of Bangladesh

Background: Live related kidney transplantation is the most preferred form of renal replacement therapy worldwide including Bangladesh. However, it is challenging and also rewarding both for patients and treating physicians. BSMMU hospital has given maximum effort for its greater success. The aim of this study was to share our ten years’ experience regarding some aspects of live related renal transplantation. Methods: This retrospective study was conducted in nephrology department of BSMMU hospital from January 2002 to December 2015. Data were collected from hospital records and some previously conducted study on these transplant recipients. Results: A total of 360 live related kidney transplant recipients were evaluated during this period. Recipients Male: Female ratio was 1.57:1. Mean age of recipients were 39.58 ± 10.46 years. The causes of ESRD were chronic glomerulonephritis 220(61.60 %), diabetic nephropathy 58(16.24%), hypertensive nephrosclerosis 22 (6.16 %), chronic interstitial nephritis 11 (3.08 %), SLE 10(2.8%), ADPKD 6(1.68 %), unknown 19(5.32 %). Most of the donors were mother (21.84% %) followed by spouse mostly wife (20.44%) and sister (18.76 %). Almost all recipients were on MHD 352(97.78%), 2 were on CAPD and 06 were pre-emptive transplantation. Triple immunosuppressive protocol Cyclosporine or Tacrolimus, MPA or Azathioprine and Prednisolone were used in each patient. Recipients with poor HLA matching received Baciliximab in standard dose. CMV prophylaxis was given in selected patients and each patient received pneumocystis jirovecii prophylaxis. Common complications during post-operative period were ATN 41(11.48%), DGF 23(6.44%), Acute rejection 50(14%) and infection mainly urinary tract infection 46(12.88%) and RTI 14(3.92) followed by wound infection and other surgical complication. Presence of BK virus infection was studied in 29 transplant recipient and it was found to be positive in 6(20.7%) cases. Protocol biopsy was done in 37 transplant recipient in the 2008-2009 on day 14, and day 90 to see subclinical rejection and early graft dysfunction. On day 14th biopsy report showed 21(56.7%) normal histology, 5(13.5%) had subclinical rejection, 5(13.5%) had clinical rejection, 4(10.8 %) developed ATN, 2(5.2 % ) cyclosporine toxicity, and report at 3 month showed normal histology 18(48.60%), subclinical rejection 7(18.90%), clinical rejection 5(10.80%). Leading cause of chronic allograft dysfunction was chronic allograft nephropathy (CAN) 60(19.80%) followed by chronic cyclosporine toxicity 37(12.21%) and de-novo or recurrent glomerulonephritis. Mean post-transplant hospital stay was 18.46 ± 5.56 days. Mean duration of normalization of serum creatinine after surgery was 7.38 ± 3.88 days. At discharge 74.40% patients had normal renal function with mean serum creatinine 1.10 ± 0.26 mg/dl and 21.34% patients showed gradual improvement of renal function with mean serum creatinine 2.12 ± 0.97 mg/dl. In our study 1 year and 5 years’ graft survival was 93.88% and 75.16% respectively and 1 year and 5 years’ patient’s survival was 346(96.08%) and 290(81.2%). Conclusion: Our report shows that short and long term graft and patient survival is encouraging and comparable to other centers of both developing and some developed countries with limited resources and facilities.

Long-term effect of eplerenone treatment in children with chronic allograft nephropathy.

Literature supports the protective role of mineralocorticoid antagonist (MRA) against the renal injury induced by aldosterone in kidney transplant recipients. However, there is limited data available regarding the safety and efficacy of MRAs in pediatric renal transplant patients. Therefore, we aimed to investigate the effect of long-term eplerenone administration in children with chronic allograft nephropathy (CAN). Twenty-six renal transplant children with biopsy-proven CAN, an estimated glomerular filtration rate (eGFR ) > 40 mL/min per 1.73 m2 and with a significant proteinuria were included. Selected patients were randomly divided into two groups as follows; Group 1 (n = 10) patients received 25 mg/day eplerenone and Group 2 (n = 16) patients did not receive eplerenone for 36 months. Patients were examined in the renal transplant outpatient clinic biweekly for the first month and once a month thereafter. The primary outcome of the patients was compared. Mean eGFR stayed stable in group 1 patients, but significantly decreased in group 2 at 36 months (57.53 ± 7.53 vs. 44.94 ± 8.04 mL/min per 1.73 m2 , p = .001). Similarly, spot protein-creatinine ratio was significantly lower in group 1 compared to group 2 patients at 36 months (1.02 ± 7.53 vs. 3.61 ± 0.53, p < .001). Eplerenone associated hyperkalemia was not observed in group 1 patients (4.6 ± 0.2 vs. 4.56 ± 0.3, p = .713). The long-term eplerenone administration blunted the chronic allograft nephropathy by maintaining a stable eGFR levels and decreasing urine protein-creatinine ratio. Eplerenone associated hyperkalemia was not observed in our study.

Evaluation of Interstitial Fibrosis and Tubular Atrophy (IFTA) in Renal Allograft Biopsies:- Comparison of Visual Analysis with Morphometric Quantification and its Correlation with Renal Function

ABSTRACT Introduction: With the increase in number of allografts being performed, the frequency of chronic allograft nephropathy (CAN) has also increased. It is characterized clinically by a progressive decline in glomerular filtration rate, and histologically, by a progressive interstitial fibrosis (IF) and tubular atrophy (TA) which can even be seen in recipients with good allograft function. Objectives: To compare visual analysis with morphometric quantification of interstitial fibrosis and tubular atrophy (IFTA) in renal allograft biopsies and its correlation with renal function. Materials and Methods: A total of 29 renal allograft biopsies were evaluated for fibrosis and tubular atrophy by light microscopy by visual method on Masson’s trichrome-stained and PAS-stained sections, respectively, as well as by computer-assisted morphometry. IFTA was graded as per Banff working classification of renal allograft pathology, which includes a four-point estimate of the prevalence of IF (ci score) and for tubular atrophy (ct score). The estimation of IF and TA by the two methods was correlated with the renal function state; the serum creatinine level. Result: The percentage of IFTA showed statistically significant correlation between manual and morphometric methods (P &lt; 0.001). Each of the method was correlated with serum creatinine level. IF showed a good correlation with serum creatinine by both the methods; however, no correlation could be established between TA and serum creatinine by either method. Conclusion: When calculating scoring IFTA as per Banff criteria, by either the visual method or the morphometric method, there was a significant correlation between the two methods. However when expressed only as a percentage of total area, the visual method was associated with slight overestimation of both the parameters.

Effects of Treating Subclinical Rejection 2 Weeks After Kidney Transplantation, as Determined by Analyzing 1-Year Histologic Outcomes

Subclinical rejection (SCR) is associated with chronic allograft nephropathy. Therefore, early detection and treatment of SCR through a protocol biopsy (PB) can reduce the incidence of pathologic changes. This study evaluates the impact of early detection and treatment of SCR using a routine PB 2 weeks after kidney transplantation (KT) by examining histologic outcomes 1 year later. We reviewed 624 KT recipients at the Samsung Medical Center between August 2012 and December 2018. Protocol biopsy was planned 2 weeks and 1 year after transplantation. We compared the histologic changes between the 2 biopsies. After a propensity score matching analysis, we divided the patients into 2 groups: the proven normal group (n=256) and the rejection group (n=96) at the PB taken 2 weeks post-transplant. The rejection group showed no significant difference from the normal group in the flow of graft function or the Kaplan-Meier curve for graft survival. In the histologic outcomes, the pathologic differences between the groups significantly improved between the 2 time points. Treating SCR through a PB 2 weeks after KT can contribute to the maintenance of graft function and improve histologic changes 1 year after KT.

Pregnancy after kidney transplantation: Ibn Sina Rabat University hospital experience

Kidney transplantation (KT) restores the fertility of women with end-stage kidney disease (ESKD), thus offering them the possibility of having children. However, pregnancy after kidney transplantation is associated with high maternal-fetal morbidity. The purpose of this work is to report the experience of our service in pregnancies in kidney transplant recipients. We retrospectively studied the records of transplant recipients who had one or more pregnancies after KT. We analyzed clinical (blood pressure, weight gain, oedema, duration of pregnancy, obstetric complication) and biological (creatinine, urinary albumin excretion) parameters. Between 1998 and 2020, twenty-one pregnancies occurred in 12 transplant recipients. The average age of patients at the time of conception was 29 ± 5 years with a delay between KT and pregnancy of 43 ± 29 months. Seven pregnancies began with arterial hypertension (HTA) controlled under treatment, proteinuria before conception was negative in all pregnancies and renal function was normal with an average creatinine level of 10.1 ± 1,27 mg/L. Prior to pregnancy, immunosuppression regimens were based on anticalcineurin (n = 21) combined either with mycophenolate mofetil (MMF) (n = 10) or azathioprine (n = 8) or alone (n = 3). Immunosuppression regimens were all associated with corticosteroid therapy. Three months before conception, MMF was relayed by azathioprine in seven pregnancies, on the other hand three other unplanned pregnancies, started under MMF. During pregnancy, the appearance of proteinuria greater than 0,5 g/24 h was noted in three pregnancies in the third trimester. Pregnancy hypertension was found in three pregnancies, one of which progressed to pre-eclampsia. As for renal function, it remained stable with an average creatinine level of 10,3 mg/l in the 3rdtrimester. Two cases of acute pyelonephritis were noted. No episode of acute rejection was noted during and 3 months after pregnancy. The delivery was performed by caesarean section in 44.4%, after an average term of 37 week of amenorrhea ± 2.04 with three cases of prematurity. The average birth weight was 3 110 g ± 450 g. There was one case of spontaneous abortion and two cases of fetal death in utero. After post-partum, renal function remained stable in five patients. In six cases, there was impaired renal function either by acute rejection or secondary to chronic allograft nephropathy. In our department, a quarter of transplant recipients were able to carry a pregnancy with a rate of 89% of successful pregnancies. Pregnancy after KT requires special planning and monitoring. A multidisciplinary collaboration between transplant nephrologist, gynecologist and pediatrician is necessary by referring to the recommendations.

Comparative Study of OD (Tacrolimus Extended-Release Capsules) Versus Conventional Tacrolimus in Renal Transplant Patients

One of the common causes of chronic allograft nephropathy is non adherence to medications contributing to 30% of graft loss in developed world. The non-adherence is attributed to pill burden. Once-daily dosing of tacrolimus instead of conventional twice-daily dosing may enhance adherence to medication and improve long-term outcomes.

"Creating Blue Skies Overhead for All" Introduction of the 2022 Recipient of the Medawar Prize of the Transplantation Society: Professor Jeremy Chapman.

"Creating Blue Skies Overhead for All" Introduction of the 2022 Recipient of the Medawar Prize of the Transplantation Society: Professor Jeremy Chapman.

Comparative study of once daily tacrolimus (extended-release capsule) versus conventional twice daily tacrolimus in renal transplant recipients

Background: One of the common causes of chronic allograft nephropathy is nonadherence to medications, contributing to 30% of graft loss in the developed world. The non-adherence is attributed predominantly to pill burden. Once-daily dosing of tacrolimus instead of conventional twice-daily dosing may enhance adherence to medication and improve long-term outcomes. The present study is a retrospective analysis comparing the safety and effectiveness of De Novo (use from day 1) once daily (OD) Tacrolimus (extended-release capsules) to conventional twice-a-day (BD) tacrolimus, in renal transplant recipients operated at Suguna Hospital Bangalore India. Material and Methods: Records of 24 Transplant patients on De novo OD Tacrolimus were analyzed and compared retrospectively to 24 transplant patients treated De Novo with conventional BD tacrolimus on a regular follow-up for at least 2 yrs. post-transplant at our center. Results: Various parameters recorded till the last follow-up were analyzed and compared. The average weight of the cohort (64.6 kg vs. 66.6 kg), average tacrolimus dose (2.7 mg vs. 2.15 mg), average Tac dose/kg body weight (0.04 mg vs. 0.03 mg), average Sr.Creatinine, at Last, Follow up (1.2 mg/dl vs. 1.32 mg/dl) were comparable in both groups and were statistically insignificant (p &gt; 0.05). However, there was a higher incidence of Post-Transplant Diabetes Mellitus (PTDM) noted in the Conventional BD Tacrolimus group (20.83%) compared to the OD Tacrolimus group (4.1%) and it was statistically significant (p = 0.17). The Infection rate of 41.67% in the conventional BD Tacrolimus group was much higher compared to the OD Tacrolimus group (4.17%) which was statistically significant (p = 0.01). There was 100% patient and graft survival at the end of two years in both groups. Tacrolimus Dose for OD and Conventional BD dosing were similar, unlike earlier studies recommending a 10% increase in dose for OD tacrolimus compared to BD dosing. Conclusion: OD Tacrolimus dose is comparable to conventional BD dose Tacrolimus in its safety and Efficacy; however, it scores over conventional BD dose Tacrolimus in terms of post-transplant infections and post-transplant diabetes mellitus (PTDM) and a more stable serum trough level.

Association between Circulating MicroRNAs (miR-21-5p, miR-20a-5p, miR-29b-3p, miR-126-3p and miR-101-3p) and Chronic Allograft Dysfunction in Renal Transplant Recipients.

Chronic allograft dysfunction (CAD) is a major condition affecting long-term kidney graft survival. Serum microRNA (miRNA) has been reported as a biomarker for various conditions of allograft injuries. The upregulation of miR-21 is the best-known miRNA change in graft tissue, urine and plasma. However, the correlation of plasma miR-21 with the severity of CAD remains unclear. In our study, 40 kidney transplantation recipients with late graft survival for more than 10 years were enrolled. The CAD group (n = 20) had either an eGFR between 15 to 60 mL/min or a biopsy-proved chronic allograft nephropathy or rejection. The control group (n = 20) had an eGFR ≥ 60 mL/min without proteinuria and hematuria for a consecutive 3 months before the study. We performed RNA sequencing to profile the miRNAs expression. There were six differentially expressed miRNAs in the CAD group. Among them, miR-21-5p and miR-101-3p were decreased, and miR-20a-5p was increased. We found that miR-21-5p, miR-20a-5p and miR-101-3p all participated in the TGF-beta pathway. We demonstrated that decreased miR-21-5p and miR-101-3p, and increased miR-20a-5p were the novel CAD-associated miRNAs in the TGF-beta pathway. These findings may pave the way for developing early prediction miRNAs biomarkers for CAD, and possibly developing therapeutic tools in the field of kidney transplantation.