High Calcineurin Inhibitor Intrapatient Variability Is Associated With Renal Allograft Inflammation, Chronicity, and Graft Loss

Introduction: Extra efferent arterioles, also known as polar vasculosis (PV), are often observed in the glomerular vascular pole and are associated with glomerular hypertrophy, indicating early recurrent diabetic kidney disease (DKD) in renal allografts. However, its significance in patients without diabetes remains uncertain. Methods: A total of 9,004 renal allograft biopsy specimens obtained between January 2007 and December 2017 at Tokyo Women’s Medical University were retrospectively analyzed to examine the clinical and pathological significance of PV in renal allografts. PV was identified in 186 biopsy specimens obtained from 165 patients. The PV group comprised 46 patients; 35 patients without DKD and 11 patients with DKD as the initial cause of ESRD, whose clinical information was available and treated with the calcineurin inhibitor (CNI) tacrolimus. The non-PV group comprising patients with renal allografts matched for age and postoperative day included 93 patients without DKD and 16 patients with DKD as the initial cause of ESRD. Results: In patients with nondiabetic renal allografts, systolic blood pressure was significantly higher in the PV group than in the non-PV group. The trough tacrolimus levels during the overall study period and at 2 weeks, 1 month, and 2 years after transplantation were significantly higher in the PV group compared with the non-PV group. Glomerulomegaly was significantly more common. Moreover, ah and aah scores in Banff score were significantly higher in the PV group than in the non-PV group. In those with diabetic renal allografts, although the clinical parameters and tacrolimus trough levels in all time periods were not significantly different between the PV and non-PV groups, the ah score was significantly higher in the PV group. Conclusion: PV was associated with CNI toxicity in nondiabetic but not in diabetic renal allografts. The pathogenesis of PV in renal allografts is considered to be multifactorial.

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Effect of steroid-free low concentration calcineurin inhibitor maintenance immunosuppression regimen on renal allograft histopathology and function

Nephrology Dialysis Transplantation ◽

10.1093/ndt/gfr608 ◽

2011 ◽

Vol 27 (5) ◽

pp. 2077-2083 ◽

Cited By ~ 6

Author(s):

N. Nainani ◽

N. Patel ◽

N. Tahir ◽

R. Kumar ◽

E. Weber-Shrikant ◽

...

Keyword(s):

Renal Allograft ◽

Calcineurin Inhibitor ◽

Low Concentration ◽

Maintenance Immunosuppression ◽

And Function ◽

Immunosuppression Regimen

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Immunosuppression with Calcineurin Inhibitor after Renal Transplant Failure Inhibits Allosensitization

Biomedicines ◽

10.3390/biomedicines8040072 ◽

2020 ◽

Vol 8 (4) ◽

pp. 72 ◽

Cited By ~ 1

Author(s):

Covadonga López del Moral Cuesta ◽

Sandra Guiral Foz ◽

David Gómez Pereda ◽

José Luis Pérez Canga ◽

Marina de Cos Gómez ◽

...

Keyword(s):

Graft Failure ◽

Calcineurin Inhibitor ◽

De Novo ◽

Immunosuppressive Treatment ◽

Graft Loss ◽

Multivariate Logistic Regression Analysis ◽

Human Leukocyte ◽

Leukocyte Antigen ◽

Single Antigen ◽

Transplant Failure

Immunosuppression withdrawal after graft failure seems to favor sensitization. A high percentage of calculated panel-reactive antibody (cPRA) and the development of de novo donor specific antibodies (dnDSA) indicate human leukocyte antigen (HLA) sensitization and may hinder the option of retransplantation. There are no established protocols on the immunosuppressive treatment that should be maintained after transplant failure. A retrospective analysis including 77 patients who lost their first renal graft between 1 January 2006–31 December 2015 was performed. Two sera were selected per patient, one immediately prior to graft loss and another one after graft failure. cPRA was calculated by Single Antigen in all patients. It was possible to analyze the development of dnDSA in 73 patients. By multivariate logistic regression analysis, the absence of calcineurin inhibitor (CNI) at 6 months after graft failure was related to cPRA > 75% (OR 4.8, CI 95% 1.5–15.0, p = 0.006). The absence of calcineurin inhibitor (CNI) at 6 months after graft loss was significantly associated with dnDSA development (OR 23.2, CI 95% 5.3–100.6, p < 0.001). Our results suggest that the absence of CNI at the sixth month after graft loss is a risk factor for sensitization. Therefore, maintenance of an immunosuppressive regimen based on CNI after transplant failure should be considered when a new transplant is planned, since it seems to prevent HLA allosensitization.

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