MO298A SPECIFIC TUBULAR APOA-I DISTRIBUTION IS ASSOCIATED TO FSGS RECURRENCE AFTER KIDNEY TRANSPLANTATION

2021 ◽  
Vol 36 (Supplement_1) ◽  
Author(s):  
Conxita Jacobs Cachá ◽  
Natàlia Puig Gay ◽  
Ander Vergara ◽  
Alejandra Gabaldon ◽  
Joana Sellares ◽  
...  
Keyword(s):  
Kidney Transplantation ◽  
Focal Segmental Glomerulosclerosis ◽  
Brush Border ◽  
Diagnostic Tool ◽  
Apical Membrane ◽  
Major Complication ◽  
Kidney Allograft ◽  
Tubular Cells ◽  
Apolipoprotein A ◽  
Positive Recurrent

Abstract Background and Aims A major complication primary focal segmental glomerulosclerosis (FSGS) is its recurrence after kidney transplantation that happens in 30 to 40% of the patients. The diagnosis of this relapses is not always easy as the histological lesions are not highly specific and appear after the proteinuria increase. Currently, there are no accurate biomarkers to detect FSGS recurrence. Our group identified a modified form of Apolipoprotein A-I (ApoA-I), named ApoA-Ib, specifically present in urine of recurrent FSGS patients after kidney transplantation. Aberrant forms of ApoA-I have also been described in urine of native primary FSGS patients and have associated this feature to a prominent staining of ApoA-I at the apical membrane of the tubular cells. In this study we aim to analyze the ApoA-I distribution in kidney allograft biopsies of recurrent FSGS patients. Method We detected ApoA-I by immunohistochemistry in kidney allograft biopsies of patients with FSGS relapse after kidney transplantation (urinary ApoA-Ib positive) and in kidney allograft biopsies of patients with a disease different from FSGS in the native kidney (No-FSGS, urinary ApoA-Ib negative). Results In ApoA-Ib positive recurrent FSGS patients, ApoA-I was prominently localized at the brush border of the tubular cells while in the No-FSGS patients ApoA-I was found along the cytoplasm of the tubular cells (Figure 1). Conclusion The localization of ApoA-I at the brush border of the tubular cells is a specific feature of primary FSGS in relapse. This suggests that ApoA-I staining in kidney biopsies, coupled with ApoA-Ib measurement in urine, could be used as a diagnostic tool of primary FSGS relapse after kidney transplantation due to its highly specific tubular distribution.

scholarly journals A Specific Tubular ApoA-I Distribution Is Associated to FSGS Recurrence after Kidney Transplantation

2021 ◽  
Vol 10 (10) ◽  
pp. 2174
Author(s):  
Conxita Jacobs-Cachá ◽  
Natàlia Puig-Gay ◽  
Ander Vergara ◽  
Maria-Alejandra Gabaldon ◽  
Joana Sellarés ◽  
...  
Keyword(s):  
Kidney Transplantation ◽  
Focal Segmental Glomerulosclerosis ◽  
Brush Border ◽  
Diagnostic Tool ◽  
Apical Membrane ◽  
Major Complication ◽  
Kidney Allograft ◽  
Tubular Cells ◽  
Apolipoprotein A ◽  
Segmental Glomerulosclerosis

A major complication of primary focal segmental glomerulosclerosis (FSGS) is its recurrence after kidney transplantation that happens in 30 to 40% of the patients. The diagnosis of these relapses is not always easy as the histological lesions are not highly specific and appear after the proteinuria increase. Currently, there are no accurate biomarkers to detect FSGS recurrence. Our group identified a modified form of Apolipoprotein A-I (ApoA-I), named ApoA-Ib, specifically present in the urine of recurrent FSGS patients after kidney transplantation. Aberrant forms of ApoA-I have also been described in the urine of native primary FSGS patients; this feature has been associated with prominent staining of ApoA-I at the apical membrane of the tubular cells. In this study, we aim to analyze the ApoA-I distribution in kidney allograft biopsies of recurrent FSGS patients. We detected ApoA-I by immunohistochemistry in kidney allograft biopsies of patients with FSGS relapse after kidney transplantation and in kidney allograft biopsies of patients with a disease different from FSGS in the native kidney (non-FSGS). In recurrent FSGS patients, ApoA-I was prominently localized at the brush border of the tubular cells, while in the non-FSGS patients, ApoA-I was found along the cytoplasm of the tubular cells. The localization of ApoA-I at the brush border of the tubular cells is a specific feature of primary FSGS in relapse. This suggests that ApoA-I staining in kidney biopsies, coupled with ApoA-Ib measurement in urine, could be used as a diagnostic tool of primary FSGS relapse after kidney transplantation due to its highly specific tubular distribution.

scholarly journals Orosomucoid 1 is involved in the development of chronic allograft rejection after kidney transplantation

2020 ◽  
Vol 32 (5) ◽  
pp. 335-346 ◽  
Author(s):  
Haruka Higuchi ◽  
Daisuke Kamimura ◽  
Jing-Jing Jiang ◽  
Toru Atsumi ◽  
Daiki Iwami ◽  
...  
Keyword(s):  
Kidney Transplantation ◽  
Kidney Transplant ◽  
Therapeutic Target ◽  
Allograft Rejection ◽  
Transplant Recipients ◽  
Kidney Transplant Recipients ◽  
Kidney Allograft ◽  
Tubular Cells ◽  
Chronic Allograft Rejection ◽  
Antibody Mediated Rejection

Abstract Chronic allograft rejection is the most common cause of long-term allograft failure. One reason is that current diagnostics and therapeutics for chronic allograft rejection are very limited. We here show that enhanced NFκB signaling in kidney grafts contributes to chronic active antibody-mediated rejection (CAAMR), which is a major pathology of chronic kidney allograft rejections. Moreover, we found that urinary orosomucoid 1 (ORM1) is a candidate marker molecule and therapeutic target for CAAMR. Indeed, urinary ORM1 concentration was significantly higher in kidney transplant recipients pathologically diagnosed with CAAMR than in kidney transplant recipients with normal histology, calcineurin inhibitor toxicity, or interstitial fibrosis and tubular atrophy. Additionally, we found that kidney biopsy samples with CAAMR expressed more ORM1 and had higher NFκB and STAT3 activation in tubular cells than samples from non-CAAMR samples. Consistently, ORM1 production was induced after cytokine-mediated NFκB and STAT3 activation in primary kidney tubular cells. The loss- and gain-of-function of ORM1 suppressed and promoted NFκB activation, respectively. Finally, ORM1-enhanced NFκB-mediated inflammation development in vivo. These results suggest that an enhanced NFκB-dependent pathway following NFκB and STAT3 activation in the grafts is involved in the development of chronic allograft rejection after kidney transplantation and that ORM1 is a non-invasive candidate biomarker and possible therapeutic target for chronic kidney allograft rejection.

Low-affinity transport of pyroglutamyl-histidine in renal brush-border membrane vesicles

1989 ◽  
Vol 257 (5) ◽  
pp. C971-C975 ◽  
Author(s):  
H. A. Skopicki ◽  
K. Fisher ◽  
D. Zikos ◽  
G. Flouret ◽  
D. R. Peterson
Keyword(s):  
Brush Border ◽  
Brush Border Membrane ◽  
Membrane Vesicles ◽  
Brush Border Membrane Vesicles ◽  
Proximal Tubular Cells ◽  
Tubular Cells ◽  
Luminal Membrane ◽  
Renal Brush Border Membrane ◽  
Proximal Tubular ◽  
Renal Brush Border

These studies were performed to determine if a low-affinity carrier is present in the luminal membrane of proximal tubular cells for the transport of the dipeptide, pyroglutamyl-histidine (pGlu-His). We have previously described the existence of a specific, high-affinity, low-capacity [transport constant (Kt) = 9.3 X 10(-8) M, Vmax = 6.1 X 10(-12) mol.mg-1.min-1] carrier for pGlu-His in renal brush-border membrane vesicles. In the present study, we sought to demonstrate that multiple carriers exist for the transport of a single dipeptide by determining whether a low-affinity carrier also exists for the uptake of pGlu-His. Transport of pGlu-His into brush-border membrane vesicles was saturable over the concentration range of 10(-5)-10(-3) M, yielding a Kt of 6.3 X 10(-5) M and a Vmax of 2.2 X 10(-10) mol.mg-1.min-1. Uptake was inhibited by the dipeptides glycyl-proline, glycyl-sarcosine, and carnosine but not by the tripeptide pyroglutamyl-histidyl-prolinamide. We conclude that 1) pGlu-His is transported across the luminal membrane of the proximal tubule by multiple carriers and 2) the lower affinity carrier, unlike the higher affinity carrier, is nonspecific with respect to other dipeptides.

scholarly journals Returning to dialysis after kidney allograft failure: the experience of the Italian Registry of Paediatric Chronic Dialysis

2021 ◽  
Author(s):  
Edoardo La Porta ◽  
Ester Conversano ◽  
Daniela Zugna ◽  
Roberta Camilla ◽  
Raffaella Labbadia ◽  
...  
Keyword(s):  
Kidney Transplantation ◽  
Chronic Dialysis ◽  
Supplementary Information ◽  
Dialysis Modality ◽  
Specific Population ◽  
Kidney Allograft ◽  
Allograft Failure ◽  
Younger Age ◽  
Complicated Course ◽  
Significant Mortality

Abstract Background The need for dialysis after kidney allograft failure (DAGF) is among the top five reasons for dialysis initiation, making this an important topic in clinical nephrology. However, data are scarce on dialysis choice after transplantation and clinical outcomes for DAGF in children. Methods Patients receiving chronic dialysis < 18 years were recorded from January 1991 to January 2019 by the Italian Registry of Pediatric Chronic Dialysis (IRPCD). We investigated factors influencing choice of dialysis modality, patient outcome in terms of mortality, switching dialysis modality, and kidney transplantation. Results Among 118 patients receiving DAGF, 41 (35%) were treated with peritoneal dialysis (PD), and 77 (65%) with haemodialysis (HD). Significant predictors for treatment with PD were younger age at dialysis start (OR 0.85 per year increase [95%CI 0.72–1.00]) and PD use before kidney transplantation (OR 8.20 [95%CI 1.82–37.01]). Patients entering DAGF in more recent eras (OR 0.87 per year increase [95%CI 0.80–0.94]) and with more than one dialysis modality before kidney transplantation (OR 0.56 for being treated with PD [0.12–2.59]) were more likely to be initiated on HD. As compared to patients on HD, those treated with PD exhibited increased but non-significant mortality risk (HR 2.15 [95%CI 0.54–8.6]; p = 0.28) and higher prevalence of dialysis-related complications during DAGF (p = 0.002) Conclusions Patients entering DAGF in more recent years are more likely to be initiated on HD. In this specific population of children, use of PD seems associated with a more complicated course. Graphical abstract A higher resolution version of the Graphical abstract is available as Supplementary information

scholarly journals Current Pharmacological Intervention and Medical Management for Diabetic Kidney Transplant Recipients

Pharmaceutics ◽  
2021 ◽  
Vol 13 (3) ◽  
pp. 413
Author(s):  
Theerawut Klangjareonchai ◽  
Natsuki Eguchi ◽  
Ekamol Tantisattamo ◽  
Antoney J. Ferrey ◽  
Uttam Reddy ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Kidney Transplantation ◽  
Kidney Transplant ◽  
Pharmacological Intervention ◽  
Diabetic Patients ◽  
Transplant Recipients ◽  
Kidney Transplant Recipients ◽  
Kidney Allograft ◽  
Post Transplant ◽  
Glucose Management

Hyperglycemia after kidney transplantation is common in both diabetic and non-diabetic patients. Both pretransplant and post-transplant diabetes mellitus are associated with increased kidney allograft failure and mortality. Glucose management may be challenging for kidney transplant recipients. The pathophysiology and pattern of hyperglycemia in patients following kidney transplantation is different from those with type 2 diabetes mellitus. In patients with pre-existing and post-transplant diabetes mellitus, there is limited data on the management of hyperglycemia after kidney transplantation. The following article discusses the nomenclature and diagnosis of pre- and post-transplant diabetes mellitus, the impact of transplant-related hyperglycemia on patient and kidney allograft outcomes, risk factors and potential pathogenic mechanisms of hyperglycemia after kidney transplantation, glucose management before and after transplantation, and modalities for prevention of post-transplant diabetes mellitus.

scholarly journals Successful long-term management of recurrent focal segmental glomerulosclerosis after kidney transplantation with costimulation blockade

2020 ◽  
Author(s):  
Thomas Mühlbacher ◽  
Kerstin Amann ◽  
Moritz Mahling ◽  
Silvio Nadalin ◽  
Nils Heyne ◽  
...  
Keyword(s):  
Kidney Transplantation ◽  
Focal Segmental Glomerulosclerosis ◽  
Costimulation Blockade ◽  
Segmental Glomerulosclerosis ◽  
Remission Maintenance ◽  
Maintenance Immunosuppression ◽  
Therapeutic Concepts ◽  
Allograft Outcome

Abstract Recurrence of primary focal segmental glomerulosclerosis (FSGS) occurs in up to 50% of patients after kidney transplantation and is associated with poor allograft outcome. Novel therapeutic concepts directly target podocyte function via B7-1 with inconsistent response. We present the case of a 19 yr. old patient with recurrent primary FSGS early after living donor kidney transplantation. Plasmapheresis and rituximab did not induce remission. Repetitive abatacept administration was able to achieve partial remission. Maintenance immunosuppression was subsequently switched to a belatacept-based CNI-free immunosuppression, resulting in sustained complete remission with excellent allograft function throughout a follow-up of more than 56 months.

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