Renal Allograft Patients Research Articles

EVALUATION OF SERUM PERIOSTIN AND PIIINP AS BIOMARKERS OF RENAL FIBROSIS AND FUNCTION DECLINE IN RENAL TRANSPLANT PATIENTS

This study aimed to evaluate the potential of serum periostin and N-terminal propeptide of type III procollagen (PIIINP) as biomarkers for predicting renal fibrosis and functional decline in renal transplant patients. We conducted a two-visit observational study among 86 renal allograft patients, reduced to 35 at the two-year follow-up due to the COVID-19 pandemic. Blood samples were collected at baseline and follow-up, while urine samples were collected only at follow-up. Serum levels of PIIINP and periostin were measured using ELISA kits, and various renal function parameters were assessed. Serum PIIINP levels showed a significant decrease over two years (p<0.001, Wilcoxon test), while periostin levels significantly increased (p<0.001, Wilcoxon test). These changes correlated with declines in renal function, as indicated by decreased serum albumin and creatinine clearance levels, and increased serum creatinine levels. Significant correlations were found between changes in PIIINP and creatinine clearance (Spearman coefficient = 0.352, p<0.05), as well as between changes in periostin and creatinine clearance (Spearman coefficient = 0.626, p<0.001). Our findings suggest that serum periostin and PIIINP levels are valuable biomarkers for assessing renal fibrosis and functional decline in renal transplant patients. These biomarkers may provide insights into disease progression and guide therapeutic interventions.

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.

Delayed-release rapamycin halts progression of left ventricular hypertrophy in subclinical feline hypertrophic cardiomyopathy: results of the RAPACAT trial.

Feline hypertrophic cardiomyopathy (HCM) remains a disease with little therapeutic advancement. Rapamycin modulates the mTOR pathway, preventing and reversing cardiac hypertrophy in rodent disease models. Its use in human renal allograft patients is associated with reduced cardiac wall thickness. We sought to evaluate the effects of once-weekly delayed-release (DR) rapamycin over 6 months on echocardiographic, biochemical, and biomarker responses in cats with subclinical, nonobstructive HCM. 43 client-owned cats with subclinical HCM. Cats enrolled in this double-blinded, multicentered, randomized, and placebo-controlled clinical trial were allocated to low- or high-dose DR rapamycin or placebo. Cats underwent physical examination, quality-of-life assessment, blood pressure, hematology, biochemistry, total T4, urinalysis, N-terminal pro-B-type natriuretic peptide, and cardiac troponin I at baseline and days 60, 120, and 180. Fructosamine was analyzed at screening and day 180. Echocardiograms were performed at all time points excluding day 120. Outcome variables were compared using a repeated measures ANCOVA. No demographic, echocardiographic, or clinicopathologic values were significantly different between study groups at baseline, confirming successful randomization. At day 180, the primary study outcome variable, maximum LV myocardial wall thickness at any location, was significantly lower in the low-dose DR rapamycin group compared to placebo (P = .01). Oral DR rapamycin was well tolerated with no significant differences in adverse events between groups. Results demonstrate that DR rapamycin was well tolerated and may prevent or delay progressive LV hypertrophy in cats with subclinical HCM. Additional studies are warranted to confirm and further characterize these results.

Observational Study of Early Outcomes in Single-Vessel and Multiple-Vessel Renal Allograft.

IntroductionEnd-stage renal disease (ESRD) is a global problem with a similar worldwide need for renal replacement therapy. However, the availability of transplant organs remains a challenge. Therefore, we conducted this study to measure early outcomes (up to one month) of renal allograft functions after renal transplant by assessing graft vascularity. We also measured the changes in serum creatinine and hemoglobin levels in single- and multiple-vessel renal allograft recipients.MethodsWe conducted an observational study of 108 renal allograft patients for two years. The study included all renal allograft recipients during the study period. The study excluded patients with a history of renal transplant, patients on antithrombotic therapy, a donor with previous surgery of graft kidney, and patients with anatomic abnormalities. Eighty-five patients were in the single-vessel group, and 23 were in the multiple-vessel group. Donors and recipients received standard pretransplant workup, including donor CT angiography and human leukocyte antigen crossmatching. We performed laparoscopic donor nephrectomies for all participants and perfused all renal arteries separately with Renograph solution (Claris Lifesciences, North Brunswick, NJ). A renal transplant was done in the right or left iliac fossa, noting warm and cold ischemia times. In single-vessel recipients, we anastomosed the renal artery to the external iliac artery (EIA), the renal vein to the external iliac vein (EIV), and the ureter to the bladder via a modified Lich-Gregoir technique. In multiple-vessel recipients, we performed bench anastomosis to make a single vessel, or we anastomosed vessels separately to the EIA, EIV, or the inferior epigastric artery for patients with a second small renal artery. We measured postoperative serum creatinine and hemoglobin levels for one month. In addition, we assessed graft vascularity with ultrasound-guided (USG) Doppler in the first postoperative week. We used IBM SPSS Statistics for Windows, version 21.0. (IBM Corp., Armonk, NY) for all data analyses.ResultsWarm ischemia time (WIT) was longer in multiple-vessel patients than in single-vessel patients, but the difference was insignificant (p=0.054). Cold ischemia time (CIT) was significantly longer in the multiple-vessel group than in the single-vessel group (p=0.048). We found no significant difference in serum creatinine or hemoglobin levels between groups during the study period. Perigraft collection occurred in three single-vessel patients and decreased vascularity in two multiple-vessel patients, according to USG Doppler.ConclusionsWe conducted this study to measure early outcomes of renal allograft functions after renal transplant by assessing graft vascularity, serum creatinine, and hemoglobin levels in single- and multiple-vessel renal allograft patients. According to our results, renal transplantation is not inferior in multiple-vessel allograft patients. We found no significant difference in serum creatinine levels one month postoperatively. Using multiple-vessel donors helps increase the limited donor pool, which is ultimately better for managing ESRD patients.

Correlation between Sonoelastography and Histopathological Findings in Evaluation of Chronic Renal Allograft Disease

Background Non-invasive evaluation tool for allograft kidney is important to predict chronic allograft dysfunction as it can be alternative to the invasive biopsy which is prone to so many complications. Sonoelastography can assess the stiffness of the allograft renal parenchyma, which is prone to undergo interstitial fibrosis.&#x0D; Objective To correlate sonoelastography with histopathology findings in the renal allografts.&#x0D; Method Sonoelastography was done in 60 renal allograft recipients prior to their biopsy for various indications. Estimated glomerular filtration rate (eGFR) of the patient were also obtained. Histopathology reports were collected to determine Banff score of interstitial fibrosis. Descriptive measurements (Mean ± standard deviation, Frequencies, Proportions) were calculated. Correlations among the variables were measured using Pearson’s correlation, independent sample t-test, and ANOVA.&#x0D; Result The mean strain index (SI) was lower in higher grades of fibrosis. There was significant difference in mean SI (F=18.264; df= 2,57; p &lt; 0.001) among the histological grades of fibrosis. Also a significant difference in SI among mild and moderate (S.E. 0.27, p value &lt; 0.001), mild and severe (S.E. 0.213, p value &lt; 0.001) as well as moderate and severe fibrosis (S.E. 0.244, p value &lt; 0.001) was seen. Significant correlation of eGFR with SI (p &lt; 0.001) was also seen.&#x0D; Conclusion Strain index, measured with sonoelastography, significantly correlated with different grades of tissue fibrosis. Thus it can be used as alternative method for evaluation of renal allograft patients to avoid complications of biopsy.

Split-Combine Click-SELEX Reveals Ligands Recognizing the Transplant Rejection Biomarker CXCL9.

Renal rejection is a major incidence in patients after kidney transplantation and associated with allograft scarring and function loss, especially in antibody-mediated rejection. Regular clinical monitoring of kidney-transplanted patients is thus necessary, but measuring donor-specific antibodies is not always predictive, and graft biopsies are time-consuming and costly and may come up with a histological result unsuspicious for rejection. Therefore, a noninvasive diagnostic approach to estimate an increased probability of kidney graft rejection by measuring specific biomarkers is highly desired. The chemokine CXCL9 is described as an early indicator of rejection. In this work, we identified clickmers and an aptamer by split-combine click-SELEX (systematic evolution of ligands by exponential enrichment) that bind CXLC9 with high affinity. The aptamers recognize native CXCL9 and maintain binding properties under urine conditions. These features render the molecules as potential binding and detector probes for developing point-of-care devices, e.g., lateral flow assays, enabling the noninvasive monitoring of CXCL9 in renal allograft patients.

Implication of TIGIT+ human memory B cells in immune regulation

Regulatory B cells (Bregs) contribute to immune regulation. However, the mechanisms of action of Bregs remain elusive. Here, we report that T cell immunoreceptor with Ig and ITIM domains (TIGIT) expressed on human memory B cells especially CD19+CD24hiCD27+CD39hiIgD−IgM+CD1c+ B cells is essential for effective immune regulation. Mechanistically, TIGIT on memory B cells controls immune response by directly acting on T cells and by arresting proinflammatory function of dendritic cells, resulting in the suppression of Th1, Th2, Th17, and CXCR5+ICOS+ T cell response while promoting immune regulatory function of T cells. TIGIT+ memory B cells are also superior to other B cells at expressing additional inhibitory molecules, including IL-10, TGFβ1, granzyme B, PD-L1, CD39/CD73, and TIM-1. Lack or decrease of TIGIT+ memory B cells is associated with increased donor-specific antibody and TFH response, and decreased Treg response in renal and liver allograft patients. Therefore, TIGIT+ human memory B cells play critical roles in immune regulation.

A ferroptosis-related gene signature for graft loss prediction following renal allograft

ABSTRACT Allogeneic kidney transplantation (renal allograft) is the most effective treatment for advanced kidney disease. Previous studies have indicated that ferroptosis participates in the progression of acute kidney injury and renal transplant failure. However, few studies have evaluated the prognostic value of ferroptosis on renal transplantation outcomes. In this study, a total of 22 differentially expressed ferroptosis-related genes (DFGs) were identified, which were mainly enriched in infection-related pathways. Next, a ferroptosis-related gene signature, including GA-binding protein transcription factor subunit beta 1 (GABPB1), cyclin-dependent kinase inhibitor 1A (CDKN1A), Toll-like receptor 4 (TLR4), C-X-C motif chemokine ligand 2 (CXCL2), caveolin 1 (CAV1), and ribonucleotide reductase subunit M2 (RRM2), was constructed to predict graft loss following renal allograft. Moreover, receiver operating characteristic (ROC) curves (area under the ROC curve [AUC] > 0.8) demonstrated the accuracy of the gene signature and univariate Cox analysis suggested that the gene signature could play an independent role in graft loss (p < 0.05). Furthermore, the nomogram and calibration plots also indicated the good prognostic capability of the gene signature. Finally, immune-related and cytokine signaling pathways were mostly enriched in renal allograft patients with poor outcomes. Considered together, a ferroptosis-related gene signature and nomogram based on DFGs were created to predict the 1-, 2- and 3- year graft loss probability of renal allograft patients.The gene signature could serve as a valuable biomarker for predicting graft loss, contributing to improving the outcome of allogeneic kidney transplantation.

Impact of HPyV9 and TSPyV coinfection on the development of BK polyomavirus viremia and associated nephropathy after kidney transplantation

BackgroundBK polyomavirus (BKPyV) persistently infects the urinary tract and causes viremia and nephropathy in kidney transplantation (KTx), recipients. In a previous study, we observed an increased incidence and load of BKPyV viremia in KTx patients coinfected with human polyomavirus 9 (HPyV9). Here we sought confirmation of this observation and explored whether novel HPyVs that have been detected in urine (HPyV9 and trichodysplasia spinulosa polyomavirus [TSPyV]) potentially aggravate BKPyV infection.MethodsA well‐characterized cohort of 209 KTx donor‐recipient pairs was serologically and molecularly analyzed for HPyV9 and TSPyV coinfection. These data were correlated with the occurrence of BKPyV viremia and BKPyVAN in the recipients within a year after KTx.ResultsSeropositivity for HPyV9 (19%) and TSPyV (89%) was comparable between donors and recipients and did not correlate with BKPyV viremia and BKPyVAN that developed in 25% and 3% of the recipients, respectively. Two recipients developed TSPyV viremia and none HPyV9 viremia. Modification of the predictive effect of donor BKPyV seroreactivity on recipient BKPyV viremia by HPyV9 and TSPyV was not observed.ConclusionsOur data provide no evidence for a promoting effect of HPyV9 and TSPyV on BKPyV infection and BKPyVAN in renal allograft patients. Therefore, we do not recommend including HPyV9 and TSPyV screening in KTx patients.

Robot-Assisted Radical Prostatectomy in a Post−Kidney Transplant Patient: An Initial Case Report in China

ObjectiveOur aim was to evaluate the general applicability, feasibility, and safety of robot-assisted radical prostatectomy (RARP) in Chinese renal allograft patients for prostate cancer removal. Patients and MethodsA 62-year-old patient diagnosed as having biopsy-proven localized prostate cancer in March 2016 who had undergone renal transplant 12 years ago was studied. The preoperative prostate-specific antigen value was determined to be 11.82 ng/mL and the Gleason score was determined to be 3 + 3. The RARP was carried out using a transperitoneal and posterior approach with 5 ports in May 2016. The most important technique was ensuring that the transplanted kidney and ureter remained untouched during the surgery. Only the right obturator lymph nodes were dissected because the renal allograft was overlying the iliac vessels. ResultsThe RARP was successfully concluded following 230 minutes with an estimated blood loss of 200 mL. There were no postoperative complications. Final pathology was T2cN0M0, Gleason 3 + 3. Following catheter removal, the patient was completely continent and was discharged with no change in serum creatinine or glomerular filtration rate levels. During a 21-month follow-up, unobstructed urination, no incontinence, no biochemical recurrence, and normal kidney function were observed. ConclusionRARP in Chinese renal allograft patients is a feasible method that can be accomplished with no injuries to the transplanted kidney or ureter and is achieved with favorable oncological and functional outcomes. In addition, post−kidney transplant male patients are recommended to have routine prostate-specific antigen screening for the early detection of prostate cancer.

Allograft and patient survival after sequential HSCT and kidney transplantation from the same donor-A multicenter analysis.

Tolerance induction through simultaneous hematopoietic stem cell and renal transplantation has shown promising results, but it is hampered by the toxicity of preconditioning therapies and graft‐versus‐host disease (GVHD). Moreover, renal function has never been compared to conventionally transplanted patients, thus, whether donor‐specific tolerance results in improved outcomes remains unanswered. We collected follow‐up data of published cases of renal transplantations after hematopoietic stem cell transplantation from the same donor and compared patient and transplant kidney survival as well as function with caliper‐matched living‐donor renal transplantations from the Austrian dialysis and transplant registry. Overall, 22 tolerant and 20 control patients were included (median observation period 10 years [range 11 months to 26 years]). In the tolerant group, no renal allograft loss was reported, whereas 3 were lost in the control group. Median creatinine levels were 85 μmol/l (interquartile range [IQR] 72‐99) in the tolerant cohort and 118 μmol/l (IQR 99‐143) in the control group. Mixed linear‐model showed around 29% lower average creatinine levels throughout follow‐up in the tolerant group (P < .01). Our data clearly show stable renal graft function without long‐term immunosuppression for many years, suggesting permanent donor‐specific tolerance. Thus sequential transplantation might be an alternative approach for future studies targeting tolerance induction in renal allograft recipients.

Calcineurin inhibitor-induced complement system activation via ERK1/2 signalling is inhibited by SOCS-3 in human renal tubule cells.

One factor that significantly contributes to renal allograft loss is chronic calcineurin inhibitor (CNI) nephrotoxicity (CIN). Among other factors, the complement (C-) system has been proposed to be involved CIN development. Hence, we investigated the impact of CNIs on intracellular signalling and the effects on the C-system in human renal tubule cells. In a qPCR array, CNI treatment upregulated C-factors and downregulated SOCS-3 and the complement inhibitors CD46 and CD55. Additionally, ERK1/-2 was required for these regulations. Following knock-down and overexpression of SOCS-3, we found that SOCS-3 inhibits ERK1/-2 signalling. Finally, we assessed terminal complement complex formation, cell viability and apoptosis. Terminal complement complex formation was induced by CNIs. Cell viability was significantly decreased, whereas apoptosis was increased. Both effects were reversed under complement component-depleted conditions. In vivo, increased ERK1/-2 phosphorylation and SOCS-3 downregulation were observed at the time of transplantation in renal allograft patients who developed a progressive decline of renal function in the follow-up compared to stable patients. The progressive cohort also had lower total C3 levels, suggesting higher complement activity at baseline. In conclusion, our data suggest that SOCS-3 inhibits CNI-induced ERK1/-2 signalling, thereby blunting the negative control of C-system activation.

Long-term outcomes of simultaneous heart and kidney transplantation in pediatric recipients.

Pediatric sHKTx has become an effective therapy for patients with combined cardiac and renal failure. Often, these patients develop human leukocyte antigen antibodies from their previous allografts and are therefore more difficult to re-transplant. We describe the largest case series of a predominantly sensitized pediatric sHKTx with emphasis on medical management and patient outcomes. Demographics, clinical characteristics, antibody, and biopsy data were retrospectively collected from University of California, Los Angeles database and correlated with short- and long-term patient and allograft outcomes of all sHKTx performed between 2002 and 2015. We identified seven pediatric patients who underwent sHKTx at our center. Mean age at time of sHKTx was 13.7years and 85.7% were re-graft patients. 57.1% were sensitized with cPRA >50% and another 57.1% had preformed donor-specific antibody. Five-year renal allograft survival and patient survival was 85.7% for both end-points. The remaining six patients are all alive (mean follow-up 78.5months) with good kidney and heart function. sHKTx in a population with increased immunological risk can be associated with good long-term outcomes and offers potential guidance to the pediatric transplant community where data are limited.

Selection for biopsy of kidney transplant patients by diffusion-weighted MRI.

To assess retrospectively whether diffusion-weighted magnetic resonance imaging (DW-MRI) allows physicians to determine the severity of histopathologic findings in biopsies of renal allograft patients with deteriorating renal function. Forty consecutive kidney transplant patients underwent DW-MRI and biopsy. Patients were assigned to one group with severe and to another group with normal or mild histopathologic findings. These two groups were compared based on a qualitative DW-MRI assessment (homo-/heterogeneity) and the combination of qualitative and quantitative DW-MRI parameters (ADC, and intravoxel incoherent motion, IVIM, parameters: D, f, D*). Sensitivity, specificity, and accuracy were determined for each parameter. Biopsy findings were severe in 25 patients and normal or mild in 15 patients. Qualitative DW-MRI led to a sensitivity of 44.0% and a specificity of 93.3%. Combined qualitative and quantitative DW-MRI led to an accuracy of 80% for both the minimal ADC (ADCmin) and the minimal perfusion fraction (fmin) with a sensitivity of 84.0% and 92.0% and a specificity of 73.3% and 60.0%, respectively. Combined qualitative and quantitative DW-MRI might allow physicians to determine the severity of histopathologic findings in biopsies of a high number of kidney transplant patients. • Qualitative DW-MRI is highly specific when predicting the severity of kidney transplant biopsy. • Allografts appearing heterogeneous on ADC are associated with severe histopathologic findings. • Combining qualitative and quantitative DW-MRI parameters improves the classification's sensitivity and accuracy. • Kidney transplant biopsies might be spared by combining qualitative and quantitative DW-MRI.

Conversion from Brand-Name Neoral to the Generic Ciqorin in Stable Renal Transplant Recipients

Background/Aims: Transplant physicians and patients are often reluctant to change to generic versions of immunosuppressive drugs with a narrow therapeutic index, such as ciclosporin (CsA). Thus, in routine follow-up for kidney transplant patients receiving CsA maintenance immunosuppressive therapy in our center, we evaluated the exchangeability of the brand name, Neoral, and the recently approved CsA generic formulation, Ciqorin. Methods: We assessed the complete 12-h CsA pharmacokinetic profile and direct measurement of glomerular filtration rate (mGFR) of 10 patients receiving stable doses of Neoral (138 ± 43 mg/day), at least 6 months after kidney transplantation (Neoral 1). The same evaluations were repeated 10 days after conversion to Ciqorin on a milligram-to-milligram basis and 10 days after reinstituting Neoral (Neoral 2). Results: The mean CsA area under the concentration-time curve increased slightly after switching from Neoral to Ciqorin (p = 0.03), but did not change significantly after Neoral was reintroduced (Neoral 1: 2,234 ± 783, Ciqorin: 2,452 ± 767, Neoral 2: 2,472 ± 784 ng × h/mL). There were no appreciable differences between the 2 CsA formulations in trough levels, maximum concentrations, or time to reach maximum concentrations. In all patients, renal function remained stable throughout the monitoring period (mGFR, Neoral 1: 52.0 ± 16.2; Ciqorin: 55.0 ± 19.0; Neoral 2: 55.8 ± 18.9 mL/min/1.73 m²), as did urinary and hematochemical parameters. Conclusions: In stable kidney transplant recipients, switching from Neoral to Ciqorin resulted in similar pharmacokinetic parameters and did not change renal allograft function, reassuring physicians and patients regarding the exchangeability of reference and generic CsA formulations.

Application of a Novel CT-Based Iliac Artery Calcification Scoring System for Predicting Renal Transplant Outcomes.

The objective of our study was to assess whether the degree and distribution of iliac artery calcifications as determined by a CT-based calcium scoring system correlates with outcomes after renal transplant. A retrospective review of renal transplant recipients who underwent CT of the pelvis within 2 years before surgery yielded 131 patients: 75 men and 56 women with a mean age of 52 years. Three radiologists assigned a separate semiquantitative score for calcification length, circumferential involvement, and morphology for the common iliac arteries and for the external iliac arteries. The operative and clinical notes were reviewed to determine which iliac arterial segment was used for anastomosis, the complexity of the operation, and whether delayed graft function (DGF) occurred. Renal allograft survival and patient survival were calculated using the Kaplan-Meier technique. Excellent interobserver agreement was noted for each calcification score category. The common iliac arteries showed significantly higher average calcification scores than the external iliac arteries for all categories. Advanced age and diabetes mellitus were independently predictive of higher scores in each category, whereas hypertension, cigarette smoking, hyperlipidemia, and sex were not. Based on multivariate analysis, only the calcification morphology score of the arterial segment used for anastomosis was independently predictive of a higher rate of surgical complexity and of DGF. None of the scores was predictive of graft or patient survival. However, patients with CT evidence of iliac arterial calcification had a lower 1-year survival after transplant than those who did not (92% vs 98%, respectively; p = 0.05). Only the calcification morphology score of the arterial segment used for anastomosis was significantly predictive of surgical complexity and of DGF. Routine pretransplant CT for calcification scoring in patients of advanced age or those with diabetes mellitus may enable selection of the optimal artery for anastomosis to optimize outcomes.

Comparison of BKV quantification using a single automated nucleic acid extraction platform and 3 real-time PCR assays

Monitoring peripheral blood for evidence of BK viremia through quantitative real-time PCR testing is an important management tool that allows for interventions that prevent nephropathy in renal allograft patients. This study compared the performance of 3 different real-time PCR assays for BKV quantification including 2 noncommercial tests (a historical assay “PEP” and 1 with improved genotypic inclusivity “V3T3”) and 1 using commercial reagents (Qiagen/artus, “artus”) after nucleic acid extraction of plasma with a single automated instrument (QIAsymphony). The measurable ranges (log10 copies/mL) were 2.7 to at least 8.0 for PEP and 2.0 to at least 8.0 for artus and V3T3 assays. Limits of detection (copies/mL) were 189, 56, and 28 for PEP, V3T3, and artus, respectively. Correlation experiments demonstrated linearity with original quantification results, although values obtained for the PEP assay were generally lower than those obtained for the V3T3 or artus assay across the measuring range. V3T3 and artus values were more closely related, although artus values were generally lower. The 3 assays returned different values from clinical plasma samples, likely due in part to variances in calibration. Low BKV concentrations were quantifiable by V3T3 and artus assays in plasmas that were previously deemed negative by PEP. These data underscore the need for monitoring with a single test to enable appropriate management decisions, and they suggest that an international preparation would be useful in harmonizing quantification of BKV viremia.

Recent advances in renal interstitial fibrosis and tubular atrophy after kidney transplantation

Although kidney transplantation has been an important means for the treatment of patients with end stage of renal disease, the long-term survival rate of the renal allograft remains a challenge. The cause of late renal allograft loss, once known as chronic allograft nephropathy, has been renamed “interstitial fibrosis and tubular atrophy” (IF/TA) to reflect the histologic pattern seen on biopsy. The mechanisms leading to IF/TA in the transplanted kidney include inflammation, activation of renal fibroblasts, and deposition of extracellular matrix proteins. Identifying the mediators and factors that trigger IF/TA may be useful in early diagnosis and development of novel therapeutic strategies for improving long-term renal allograft survival and patient outcomes. In this review, we highlight the recent advances in our understanding of IF/TA from three aspects: pathogenesis, diagnosis, and treatment.

Renal Outcomes After Treatment With Intensive Plasmapheresis and Intravenous Immunoglobulin in Renal Allograft Patients With Antibody-Mediated Rejection: A Single-Center Experience.

Renal Outcomes After Treatment With Intensive Plasmapheresis and Intravenous Immunoglobulin in Renal Allograft Patients With Antibody-Mediated Rejection: A Single-Center Experience.

Population PKPD of voclosporin in renal allograft patients

The aims of this population-pharmacokinetic/pharmacodynamic (POP-PKPD) analysis of voclosporin in renal allograft patients were to build a POP-PKPD model for voclosporin and calcineurin activity (CNa) and identify clinically relevant covariates that could assist dosing of the drug. POP-PKPD modeling was performed using a stochastic approximation of the standard expectation maximization (SAEM) algorithm for nonlinear mixed-effects as implemented in Monolix™ 3.2. Voclosporin whole blood concentrations were obtained from de novo renal allograft patients and assayed using a validated LC/MS/MS assay. CNa was measured using a (32)P-radiolabeled assay. A two-compartment model with simultaneous sigmoid inhibitory Emax model was used to describe the PKPD relationship between voclosporin concentration and CNa. The POP-PKPD model was then utilized to simulate an optimal initial dosing strategy. Eighty-seven patients were included in the POP-PKPD study. Population mean estimates (relative standard error, rse) for oral clearance (CL/F) and first compartment volume of distribution (V1), were 717 mL min(-1) (35%) and 2010 mL (17%), respectively. Maximum CNa Inhibition (Imax), effective concentration (C50), and baseline immunosuppression (S0) were 0.87 pmol/min/mg (8.0%), 123 ng/mL (10%), and 1.15 pmol/min/mg (4.0%), respectively. Covariate analyses demonstrated that age and body surface area significantly influenced CL/F: CLi=717(Agei/48.8)-0.57(BSAi/1.99)1.1, while serum triglycerides significantly altered S0: S0i=1.15(TRIGi/1.97)0.15.