scholarly journals Kidney Structural Features from Living Donors Predict Graft Failure in the Recipient

2020 ◽  
Vol 31 (2) ◽  
pp. 415-423 ◽  
Author(s):  
Naim Issa ◽  
Camden L. Lopez ◽  
Aleksandar Denic ◽  
Sandra J. Taler ◽  
Joseph J. Larson ◽  
...  
Keyword(s):  
Graft Failure ◽  
Clinical Characteristics ◽  
Interstitial Fibrosis ◽  
Kidney Transplant Recipient ◽  
Structural Features ◽  
Living Donors ◽  
Nephron Number ◽  
Tubular Atrophy ◽  
Cross Sectional ◽  
Arteriolar Hyalinosis

BackgroundNephrosclerosis, nephron size, and nephron number vary among kidneys transplanted from living donors. However, whether these structural features predict kidney transplant recipient outcomes is unclear.MethodsOur study used computed tomography (CT) and implantation biopsy to investigate donated kidney features as predictors of death-censored graft failure at three transplant centers participating in the Aging Kidney Anatomy study. We used global glomerulosclerosis, interstitial fibrosis/tubular atrophy, artery luminal stenosis, and arteriolar hyalinosis to measure nephrosclerosis; mean glomerular volume, cortex volume per glomerulus, and mean cross-sectional tubular area to measure nephron size; and calculations from CT cortical volume and glomerular density on biopsy to assess nephron number. We also determined the death-censored risk of graft failure with each structural feature after adjusting for the predictive clinical characteristics of donor and recipient.ResultsThe analysis involved 2293 donor-recipient pairs. Mean recipient follow-up was 6.3 years, during which 287 death-censored graft failures and 424 deaths occurred. Factors that predicted death-censored graft failure independent of both donor and recipient clinical characteristics included interstitial fibrosis/tubular atrophy, larger cortical nephron size (but not nephron number), and smaller medullary volume. In a subset with 12 biopsy section slides, arteriolar hyalinosis also predicted death-censored graft failure.ConclusionsSubclinical nephrosclerosis, larger cortical nephron size, and smaller medullary volume in healthy donors modestly predict death-censored graft failure in the recipient, independent of donor or recipient clinical characteristics. These findings provide insights into a graft’s “intrinsic quality” at the time of donation, and further support the use of intraoperative biopsies to identify kidney grafts that are at higher risk for failure.

scholarly journals HbA1c and Aortic Calcification Index as Noninvasive Predictors of Pre-Existing Histopathological Damages in Living Donor Kidney Transplantation

2020 ◽  
Vol 9 (10) ◽  
pp. 3266
Author(s):  
Kosuke Tanaka ◽  
Shigeyoshi Yamanaga ◽  
Yuji Hidaka ◽  
Sho Nishida ◽  
Kohei Kinoshita ◽  
...  
Keyword(s):  
Interstitial Fibrosis ◽  
Psoas Muscle ◽  
Living Donors ◽  
Aortic Calcification ◽  
Related Factors ◽  
Tubular Atrophy ◽  
Cross Sectional ◽  
Living Kidney Donors ◽  
Significant Difference ◽  
And Control

We previously reported that allografts from living donors may have pre-existing histopathological damages, defined as the combination of interstitial fibrosis (ci), tubular atrophy (ct), and arteriolar hyalinosis (ah) scores of ≧1, according to the Banff classification. We examined preoperative characteristics to identify whether the degree of these damages was related to metabolic syndrome-related factors of donors. We conducted a single-center cross-sectional analysis including 183 living kidney donors. Donors were divided into two groups: chronic change (ci + ct ≧ 1 ∩ ah ≧ 1, n = 27) and control (n = 156). Preoperative characteristics, including age, sex, blood pressure, hemoglobin A1c (HbA1c), aortic calcification index (ACI), and psoas muscle index (PMI), were analyzed. Comparing the groups, the baseline estimated glomerular filtration rate was not significantly different; however, we observed a significant difference for ACI (p = 0.009). HbA1c (p = 0.016) and ACI (p = 0.006) were independent risk factors to predict pre-existing histopathological damages, whereas PMI was not. HbA1c correlated with ct scores (p = 0.035), and ACI correlated with ci (p = 0.005), ct (p = 0.021), and ah (p = 0.017). HbA1c and ACI may serve as preoperative markers for identifying pre-existing damages on the kidneys of living donors.

scholarly journals Clinical characteristics and renal prognosis associated with interstitial fibrosis and tubular atrophy (IFTA) and vascular injury in lupus nephritis biopsies

2019 ◽  
Vol 49 (3) ◽  
pp. 396-404 ◽  
Author(s):  
Cianna Leatherwood ◽  
Cameron B. Speyer ◽  
Candace H. Feldman ◽  
Kristin D'Silva ◽  
José A. Gómez-Puerta ◽  
...  
Keyword(s):  
Lupus Nephritis ◽  
Vascular Injury ◽  
Clinical Characteristics ◽  
Interstitial Fibrosis ◽  
Tubular Atrophy ◽  
Renal Prognosis

Kidney Transplantation 2: Care of the Kidney Transplant Recipient

2017 ◽  
Author(s):  
Jamil Azzi ◽  
Belinda T. Lee ◽  
Anil Chandraker ◽  
Martina M McGrath
Keyword(s):  
Renal Transplantation ◽  
Interstitial Fibrosis ◽  
Kidney Transplant Recipient ◽  
Immune Monitoring ◽  
Renal Transplant Recipients ◽  
Transplant Recipients ◽  
Tubular Atrophy ◽  
Active Monitoring ◽  
Risk Factor Management ◽  
Management Of Complications

Renal transplantation is the preferred therapy for patients with end-stage kidney disease, leading to increased life expectancy, improved quality of life, and reduced health care resource use. Owing to their preexisting burden of disease, caring for renal transplant recipients is complex. Patient management following successful renal transplantation involves a multifactorial approach to cardiovascular risk factor management, along with titration of immunosuppression, management of complications related to immunosuppression, and active monitoring of allograft function. Recent advances in immunosuppressive management hold promise for improved long-term allograft survival. Finally, immune monitoring of transplant recipients is an area of considerable research, with the ultimate aim of individualized management of immunosuppression and the ability to induce transplant-specific tolerance. This review contains 7 figures,7 tables, and 117 references. Key words: cardiovascular disease, drug interactions, immunosuppression, infection, interstitial fibrosis and tubular atrophy, malignancy, rejection, tolerance

scholarly journals Procurement Biopsies in the Evaluation of Deceased Donor Kidneys

2018 ◽  
Vol 13 (12) ◽  
pp. 1876-1885 ◽  
Author(s):  
Dustin Carpenter ◽  
S. Ali Husain ◽  
Corey Brennan ◽  
Ibrahim Batal ◽  
Isaac E. Hall ◽  
...  
Keyword(s):  
Confidence Interval ◽  
Vascular Disease ◽  
Graft Failure ◽  
Interstitial Fibrosis ◽  
Frozen Section ◽  
Deceased Donor ◽  
Hazard Ratio ◽  
Donor Kidney ◽  
Tubular Atrophy ◽  
Deceased Donor Kidney

Background and objectivesBiopsies taken at deceased donor kidney procurement continue to be cited as a leading reason for discard; however, the reproducibility and prognostic capability of these biopsies are controversial.Design, setting, participants, & measurementsWe compiled a retrospective, single-institution, continuous cohort of deceased donor kidney transplants performed from 2006 to 2009. Procurement biopsy information—percentage of glomerulosclerosis, interstitial fibrosis/tubular atrophy, and vascular disease—was obtained from the national transplant database. Using univariable, multivariable, and time-to-event analyses for death-censored graft survival, we compared procurement frozen section biopsy reports with reperfusion paraffin-embedded biopsies read by trained kidney pathologists (n=270). We also examined agreement for sequential procurement biopsies performed on the same kidney (n=116 kidneys).ResultsFor kidneys on which more than one procurement biopsy was performed (n=116), category agreement was found in only 64% of cases (κ=0.14). For all kidneys (n=270), correlation between procurement and reperfusion biopsies was poor: overall, biopsies were classified into the same category (optimal versus suboptimal) in only 64% of cases (κ=0.25). This discrepancy was most pronounced when categorizing percentage of glomerulosclerosis, which had 63% agreement (κ=0.15). Interstitial fibrosis/tubular atrophy and vascular disease had agreement rates of 82% (κ=0.13) and 80% (κ=0.15), respectively. Ninety-eight (36%) recipients died, and 56 (21%) allografts failed by the end of follow-up. Reperfusion biopsies were more prognostic than procurement biopsies (hazard ratio for graft failure, 2.02; 95% confidence interval, 1.09 to 3.74 versus hazard ratio for graft failure, 1.30; 95% confidence interval, 0.61 to 2.76), with procurement biopsies not significantly associated with graft failure.ConclusionsWe found that procurement biopsies are poorly reproducible, do not correlate well with paraffin-embedded reperfusion biopsies, and are not significantly associated with transplant outcomes.

scholarly journals Pilot Analysis of Late Conversion to Belatacept in Kidney Transplant Recipients for Biopsy-Proven Chronic Tacrolimus Toxicity

2018 ◽  
Vol 2018 ◽  
pp. 1-6 ◽  
Author(s):  
Shruti Gupta ◽  
Ivy Rosales ◽  
David Wojciechowski
Keyword(s):  
Interstitial Fibrosis ◽  
Calcineurin Inhibitors ◽  
Transplant Recipients ◽  
Kidney Transplant Recipients ◽  
Tubular Atrophy ◽  
Transplant Patients ◽  
Number Of Patients ◽  
Allograft Function ◽  
The Mean ◽  
Arteriolar Hyalinosis

Background. Calcineurin inhibitors are associated with chronic nephrotoxicity, manifesting as interstitial fibrosis/tubular atrophy (IF/TA) and arteriolar hyalinosis. Conversion from tacrolimus to belatacept may be one strategy to preserve renal function. Methods. We conducted a retrospective review of renal transplant patients followed at our institution who were converted to belatacept and found to have chronic tacrolimus toxicity on biopsy. The primary outcome was eGFR at conversion as compared to eGFR at 3, 6, 12, and 24 months after conversion. We also assessed incidence of infection and rates of allograft survival at 1 year. Results. The average time between transplant and conversion was 11.9 years. There was no decrease in eGFR at any postconversion time point as compared with preconversion. The mean eGFR at time of preconversion was 32.9 mL/min, as compared with 35.6 mL/min at 3 months (p=0.09), 34.1 mL/min at 6 months (p=0.63), 34.9 mL/min at 12 months (p=0.57), and 39.6 mL/min at 24 months after conversion (p=0.92). Four of 7 patients had increases in their eGFR after conversion. All grafts were functioning at 1 year after conversion. Conclusion. While this study was limited by a small number of patients, belatacept conversion stabilized eGFR at all time points in patients with late allograft function due to chronic tacrolimus toxicity, with a trend towards increased eGFR at 3 months.

scholarly journals Membrane attack complex (MAC) deposition in renal tubules is associated with interstitial fibrosis and tubular atrophy: a pilot study

2022 ◽  
Vol 9 (1) ◽  
pp. e000576
Author(s):  
Shudan Wang ◽  
Ming Wu ◽  
Luis Chiriboga ◽  
Briana Zeck ◽  
Beatrice Goilav ◽  
...  
Keyword(s):  
Interstitial Fibrosis ◽  
Membrane Attack Complex ◽  
Staining Intensity ◽  
Cross Sectional Study ◽  
Renal Tubules ◽  
Tubulointerstitial Injury ◽  
Tubular Atrophy ◽  
Cross Sectional ◽  
Stage Renal Disease ◽  
Complement C9

IntroductionTreatment failures for lupus nephritis (LN) are high with 10%–30% of patients progressing to end-stage renal disease (ESRD) within 10 years. Interstitial fibrosis/tubular atrophy (IFTA) is a predictor of progression to ESRD. Prior studies suggest that tubulointerstitial injury secondary to proteinuria in LN is mediated by complement activation in the tubules, specifically through the membrane attack complex (MAC). This study aimed to investigate the associations between tubular MAC deposition with IFTA and proteinuria.MethodsIn this cross-sectional study, LN kidney biopsies were assessed for MAC deposition by staining for Complement C9, a component of the MAC. Chromogenic immunohistochemistry was performed on paraffin-embedded human renal biopsy sections using unconjugated, murine anti-human Complement C9 (Hycult Biotech, clone X197). Tubular C9 staining intensity was analysed as present versus absent. IFTA was defined as minimal (<10%), mild (10%–24%), moderate (25%–50%) and severe (>50%).ResultsRenal biopsies from 30 patients with LN were studied. There were 24 (80%) female sex, mean age (SD) was 33 (12) years old and 23 (77%) had pure/mixed proliferative LN. Tubular C9 staining was present in 7 (23%) biopsies. 27 patients had minimal-to-mild IFTA and 3 patients had moderate IFTA. Among the C9 + patients, 3 (43%) had moderate IFTA as compared with none in the C9- group, p=0.009. C9 + patients had higher median (IQR) proteinuria as compared with C9- patients: 6.2 g (3.3–13.1) vs 2.4 g (1.3–4.6), p=0.001 at the time of biopsy. There was no difference in estimated glomerular filtration rate (eGFR) between the C9 + and C9- groups.ConclusionThis study demonstrated that tubular MAC deposition is associated with higher degree of IFTA and proteinuria, which are predictors of progression to ESRD. These results suggest that tubular MAC deposition may be useful in classification of LN. Understanding the role of complement in tubulointerstitial injury will also identify new avenues for LN treatment.

A Higher Foci Density of Interstitial Fibrosis and Tubular Atrophy Predicts Progressive Chronic Kidney Disease after a Radical Nephrectomy for Tumor

2021 ◽  
pp. ASN.2021020267
Author(s):  
Luisa Ricaurte ◽  
Aleksandar Denic ◽  
Aidan Mullan ◽  
Ramya Narasimhan ◽  
Marija Bogojevic ◽  
...  
Keyword(s):  
Chronic Kidney Disease ◽  
Kidney Disease ◽  
Radical Nephrectomy ◽  
Clinical Characteristics ◽  
Interstitial Fibrosis ◽  
Tubulointerstitial Injury ◽  
Tubular Atrophy ◽  
Cox Models ◽  
Lower Egfr ◽  
Global Glomerulosclerosis

Background Chronic tubulointerstitial injury on kidney biopsy is usually quantified by the percentage of cortex with interstitial fibrosis/tubular atrophy (IF/TA). Whether other patterns of IF/TA or inflammation in the tubulointerstitium have prognostic importance beyond percentage IF/TA is unclear. Methods We obtained, stained, and digitally scanned full cortical thickness wedge sections of renal parenchyma from patients who underwent a radical nephrectomy for tumor in 2000 to 2015 and morphometrically analyzed the tubulointerstitium of the cortex for percentage IF/TA, IF/TA density (foci per mm2 cortex), percentage subcapsular IF/TA, striped IF/TA, percentage inflammation (both within and outside IF/TA regions), and percentage subcapsular inflammation. Patients were followed with visits every 6-12 months. Progressive chronic kidney disease (CKD) was defined as dialysis, kidney transplantation, or 40% decline from the postnephrectomy estimated glomerular filtration rate (eGFR). Cox models assessed risk of CKD or noncancer mortality with morphometric measures of tubulointerstitial injury after adjustment for percentage IF/TA and clinical characteristics. Results Among 936 patients (mean age, 64 years; postnephrectomy baseline eGFR, 48 ml/min per 1.73m2), 117 progressive CKD events and 183 noncancer deaths occurred over a median 6.4 years. Higher IF/TA density predicted both progressive CKD and noncancer mortality after adjustment for percentage IF/TA and predicted progressive CKD after further adjustment for clinical characteristics. Independent of percentage IF/TA, age, and sex, higher IF/TA density correlated with lower eGFR, smaller nonsclerosed glomeruli, more global glomerulosclerosis, and smaller total cortical volume. Conclusions Higher density of IF/TA foci (a more scattered pattern with more and smaller foci) predicts higher risk of progressive CKD after radical nephrectomy compared with the same percentage of IF/TA but with fewer and larger foci.

Interpreting CD56+ and CD163+ Infiltrates in Early versus Late Renal Transplant Biopsies

2015 ◽  
Vol 41 (4-5) ◽  
pp. 362-369 ◽  
Author(s):  
Sung Shin ◽  
Young Hoon Kim ◽  
Yong Mee Cho ◽  
Yangsoon Park ◽  
Seungbong Han ◽  
...  
Keyword(s):  
Kidney Transplant ◽  
Graft Failure ◽  
Interstitial Fibrosis ◽  
Human Kidney ◽  
The Other ◽  
Cell Infiltration ◽  
Tubular Atrophy ◽  
Antibody Mediated Rejection ◽  
Other Hand ◽  
Histologic Lesion

Background: CD56+ and CD163+ cell infiltration in human kidney transplant biopsies have not been fully evaluated. Methods: We investigated the association of CD56+ and CD163+ cell infiltration with human kidney transplant biopsies with antibody- or T-cell-mediated rejection (TCMR) and other histologic lesions. One hundred and seventy four clinically indicated transplant biopsies were included in this analysis. Immunohistochemical staining for C4d, CD56 and CD163 was performed. Results: One hundred and seventy four indication biopsies were divided into early (≤1 year posttransplant; n = 49) and late (>1 year posttransplant; n = 125) biopsies. High numbers of CD56+ cells were uncommon in early biopsies except for those with antibody-mediated rejection (AMR) only. On the other hand, high numbers of CD56+ cells were observed in late biopsies diagnosed as TCMR only, AMR only, and TCMR combined with AMR. In early biopsies, both CD56+ and CD163+ infiltrates correlated strongly with interstitial inflammation, tubulitis, and peritubular capillaritis (ptc) scores. The ci and ct scores, however, were correlated only with the number of CD56+ cells. In late biopsies, on the other hand, the number of CD56+ infiltrates was correlated only with ptc, while the number of CD163+ infiltrates was weakly correlated with any histologic lesion. Multivariable analyses showed that chronic active AMR and the number of CD56+ cells/10 HPF were independently associated with death-censored graft failure post-biopsy. The number of CD163+ cells was not correlated with any pathologic lesion and post-biopsy graft failure. CD56+ infiltrates were also associated with interstitial fibrosis and tubular atrophy. Conclusions: Intragraft CD56+ cell infiltrates were significantly associated with AMR and subsequent poor clinical outcomes.

Kidney Transplantation 2: Care of the Kidney Transplant Recipient

2017 ◽  
Author(s):  
Jamil Azzi ◽  
Belinda T. Lee ◽  
Anil Chandraker ◽  
Martina M McGrath
Keyword(s):  
Renal Transplantation ◽  
Interstitial Fibrosis ◽  
Kidney Transplant Recipient ◽  
Immune Monitoring ◽  
Renal Transplant Recipients ◽  
Transplant Recipients ◽  
Tubular Atrophy ◽  
Active Monitoring ◽  
Risk Factor Management ◽  
Management Of Complications

Renal transplantation is the preferred therapy for patients with end-stage kidney disease, leading to increased life expectancy, improved quality of life, and reduced health care resource use. Owing to their preexisting burden of disease, caring for renal transplant recipients is complex. Patient management following successful renal transplantation involves a multifactorial approach to cardiovascular risk factor management, along with titration of immunosuppression, management of complications related to immunosuppression, and active monitoring of allograft function. Recent advances in immunosuppressive management hold promise for improved long-term allograft survival. Finally, immune monitoring of transplant recipients is an area of considerable research, with the ultimate aim of individualized management of immunosuppression and the ability to induce transplant-specific tolerance. This review contains 7 figures,7 tables, and 117 references. Key words: cardiovascular disease, drug interactions, immunosuppression, infection, interstitial fibrosis and tubular atrophy, malignancy, rejection, tolerance

scholarly journals FC 120MAGNETIC RESONANCE IMAGING TEXTURE ANALYSIS PREDICTS INTERSTITIAL FIBROSIS / TUBULAR ATROPHY IN TRANSPLANTED KIDNEYS: A SINGLE CENTER CROSS-SECTIONAL STUDY

2021 ◽  
Vol 36 (Supplement_1) ◽  
Author(s):  
Francesco Fontana ◽  
Filippo Monelli ◽  
Alessia Piccinini ◽  
Giulia Besutti ◽  
Valeria Trojani ◽  
...  
Keyword(s):  
Machine Learning ◽  
Texture Analysis ◽  
Interstitial Fibrosis ◽  
Clinical Indication ◽  
Kidney Graft ◽  
Single Center ◽  
Resonance Imaging ◽  
Tubular Atrophy ◽  
Cross Sectional ◽  
Post Contrast

Abstract Background and Aims Interstitial fibrosis / tubular atrophy (IFTA) is a common, irreversible and progressive form of chronic allograft injury, and it is considered a critical predictor of kidney allograft outcomes. Inflammation, both microvascular and interstitial, is on the contrary regarded as a reversible form of graft injury. Since treatments for rejection and other causes of graft dysfunction bear substantial toxicity and could have limited efficacy, the extent of irreversible graft scarring is a crucial information for the clinician, to evaluate risks and benefits of specific therapies. The diagnosis of kidney graft pathology is acquired through graft biopsy, which is an invasive procedure and can be subjected to sampling bias. Magnetic resonance imaging (MRI), especially with functional techniques, has emerged as a possibility for non-invasive estimation of tissue fibrosis; nevertheless, functional MRI is not widely available. Texture analysis MRI (TA-MRI) is a radiomic technique that provides a quantitative assessment of tissue heterogeneity from standard MRI images, generating features that can be fitted into a machine-learning model to assess their ability to predict clinical or histological parameters. Method Single-center cross-sectional observational cohort study enrolling kidney transplant recipients who underwent graft biopsy and graft MRI imaging within 6 months from biopsy, both on clinical indication, at the “Azienda Ospedaliero-Universitaria di Modena”, Italy. The study was approved by the local Ethical Committee (AOU0010167/20). The primary outcome was to identify the best TA-MRI features subset for estimation of IFTA &gt; 50% in graft biopsy. Secondary outcomes were estimation of: IFTA &gt; 25%, presence of total inflammation (ti) and microvascular inflammation (glomerulitis + peritubular capillaritis [g+ptc]). Graft biopsy was reported according to Banff 2017 system. Radiomic analysis was performed on axial T2 pre-contrast and T1 fat-suppressed post-contrast sequences. The whole renal parenchyma (PAR) was segmented and labelled on T2 and T1, renal cortex (COR) only on T2. After imaging preprocessing, PyRadiomics was used to extract radiomic features. After removal of shape features, 93 features were included and reduced using LASSO regression to produce radiomic signatures. These were introduced in Machine Learning (ML) models to test the association with outcomes. Results are reported as AUC and a value of sensitivity and specificity. Results Sixty patients were included in the study, and 67 graft biopsy – graft MRI pairs were available for analysis. Demographic and clinical characteristics of enrolled patients are depicted in table 1; histological diagnosis and main Banff histological parameters from graft biopsies in table 2. Among ML models, three showed an acceptable performance. T2 COR “firstorder_minimum/firstorder_range/glrlm_run_entropy” for IFTA&gt;50% (AUC=0.77, sensitivity=73%, specificity=71%), T1 PAR “firstorder_energy” for IFTA&gt;25% (AUC=0.71, sensitivity=74%, specificity=51%), T1 PAR “firstorder_energy/gldm_small_dependence_low_gray_level_emphasis” for g+ptc &gt;0 (AUC=0.74, sensitivity= 78%, specificity=68%); see figures 1–3. No acceptable prediction was detected for ti &gt;0. Conclusion Our study shows that TA-MRI feature signatures can predict the degree of IFTA in graft biopsies, with an acceptable diagnostic performance. These results suggest to further investigating TA-MRI from standard MRI sequences as potential tool to assess graft chronic parenchymal injury. Moreover, since graft biopsy results can be jeopardized by limited sample size, we hypothesize that evaluation of IFTA through TA-MRI could provide more comprehensive information regarding the whole parenchyma. To test this hypothesis, we are currently evaluating the association of TA-MRI radiomic features and baseline eGFR and eGFR variation over time.

Sign in / Sign up

Export Citation Format

Share Document