Persistent Post-Transplant Autonomous Hyperparathyroidism despite 23 Years of Excellent Renal Allograft Function

Abstract Background and Aims Pulse pressure (PP) is associated with risk of kidney disease. Association between visit-to-visit PP variability (VVPPV) and renal allograft outcomes is unknown. Method VVPPV, variation of PP between each consecutive BP measurement at 4, 12, 24, 36, and 48 weeks after kidney transplantation (KT), was determined by using coefficient of variation (CV = SD/Mean x 100%). VVPPV was then categorized into 12 strata (<5, 5 - <10, 10 - <15, 15 - <20, 20 - <25, 25 - <30, 30 - <35, 35 - <40, 40 - <45, 45 - <50, 50 - <55, and ≥55). Association between the categorized VVPPV and progression of renal allograft function, which was defined by a decrease in estimated glomerular filtration rate (eGFR) after 12-week post-KT, was examined by Cox proportional hazard regression analysis. Results Of all 102 renal transplant recipients from a single kidney transplant center, mean age±SD was 54.16±11.73 years and 63 patients (62%) was female. An incidence rate of worsening renal allograft function after 12-week post-KT was 0.017 person-weeks with a median survival time of 36 weeks (Figure 1). Every 5% increase in CV of PP was associated with a 14% increased risk of worsening post-transplant eGFR (hazard ratio (HR) 1.142431, 95% confidence interval (CI) 0.9999617 to 1.305199, and p value 0.050). After adjusted for age, gender, types of induction immunosuppressive medications, pretransplant body mass index category, every increase in 5% CV of PP was significantly associated with a 16% greater risk of worsening post-transplant eGFR (HR 1.160975, 95% CI 1.007967 to 1.337209, and p value 0.038). Conclusion VVPPV is an independent predictor of worsening renal allograft function.

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MO967A STUDY OF ACUTE KIDNEY INJURY IN RENAL ALLOGRAFT RECIPIENTS AND ITS IMPACT ON SHORT-TERM OUTCOME OF GRAFT FUNCTION

Nephrology Dialysis Transplantation ◽

10.1093/ndt/gfab110.0046 ◽

2021 ◽

Vol 36 (Supplement_1) ◽

Author(s):

Manzoor Parry

Keyword(s):

Acute Kidney Injury ◽

Kidney Disease ◽

Renal Allograft ◽

Graft Function ◽

Kidney Injury ◽

Term Outcome ◽

Post Transplant ◽

Native Kidney ◽

Allograft Function

Abstract Background and Aims Acute kidney injury (AKI) in renal allograft recipients (RAR) is an important factor for short and long-term allograft function and survival. RAR are at high risk of AKI. The etiology, risk factors, and outcomes of AKI in RAR differ from that of AKI in the community setting. This study aimed to evaluate the spectrum and impact of AKI episodes on RAR outcome. Method This was a single-centre, prospective observational study on 84 live RAR patients who developed 105 AKI episodes as per Kidney Disease Improving Global Outcome (KDIGO) criteria between January 2018 to December 2019. The severity of AKI was categorized as per KDIGO guidelines. Acute rejection, recurrence of native kidney disease, and de nova glomerulonephritis were diagnosed by graft biopsy. These patients were followed for 3 months after AKI episodes. Results The mean age of our study populations was 38.1 ± 13.2 years. Mean serum creatinine at the time of AKI episode was 2.63 ± 0.95 mg/dL. The causes of AKI in our study population were infections (n 48, 45.7% ), dehydration (n 25, 23.8%), biopsy-proven rejection (n 9,8.6%) calcineurin inhibitor toxicity (n 10, 9.5%), biopsy-proven acute tubular necrosis (n 4, 3.8%), recurrence of native kidney disease (n 4, 3.8%), and miscellaneous causes (n 5, 4.8%). Most of the AKI episodes (62.9%) developed in the first year of the transplant, while as 29 (27.6%) cases developed between 1st and 2nd post-transplant year and 10 (9.5%) cases developed AKI beyond 2 years post-transplant. Sixty-four cases (60.9%) of AKI were in KDIGO stage 1, 30 cases (28.6%) were in AKI stage 2 and 11 cases (10.5%) were in AKI stage 3. Previous episodes of AKI (p<0.0001), need for dialysis at the time of AKI (p=0.0016), and higher stage of AKI (p<0.0001) were the factors associated with nonrecovery of graft functions at 3 months follow-up. At 3 months of follow up, AKI had a significant impact on allograft function. Conclusion In our study, AKI in RAR had a significant impact on allograft function. Multiple episodes of AKI, need for dialysis, and higher stage of AKI appear to affect the renal recovery at 3 months post-AKI.

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Preservation of epoxyeicosatrienoic acid bioavailability prevents renal allograft dysfunction and cardiovascular alterations in kidney transplant recipients

Scientific Reports ◽

10.1038/s41598-021-83274-1 ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Thomas Duflot ◽

Charlotte Laurent ◽

Anne Soudey ◽

Xavier Fonrose ◽

Mouad Hamzaoui ◽

...

Keyword(s):

Endothelial Function ◽

Kidney Transplant ◽

Plasma Levels ◽

Renal Allograft ◽

Transplant Recipients ◽

Loss Of Function ◽

Kidney Transplant Recipients ◽

Allograft Dysfunction ◽

Allograft Function ◽

The Impact

AbstractThis study addressed the hypothesis that epoxyeicosatrienoic acids (EETs) synthesized by CYP450 and catabolized by soluble epoxide hydrolase (sEH) are involved in the maintenance of renal allograft function, either directly or through modulation of cardiovascular function. The impact of single nucleotide polymorphisms (SNPs) in the sEH gene EPHX2 and CYP450 on renal and vascular function, plasma levels of EETs and peripheral blood monuclear cell sEH activity was assessed in 79 kidney transplant recipients explored at least one year after transplantation. Additional experiments in a mouse model mimicking the ischemia–reperfusion (I/R) injury suffered by the transplanted kidney evaluated the cardiovascular and renal effects of the sEH inhibitor t-AUCB administered in drinking water (10 mg/l) during 28 days after surgery. There was a long-term protective effect of the sEH SNP rs6558004, which increased EET plasma levels, on renal allograft function and a deleterious effect of K55R, which increased sEH activity. Surprisingly, the loss-of-function CYP2C9*3 was associated with a better renal function without affecting EET levels. R287Q SNP, which decreased sEH activity, was protective against vascular dysfunction while CYP2C8*3 and 2C9*2 loss-of-function SNP, altered endothelial function by reducing flow-induced EET release. In I/R mice, sEH inhibition reduced kidney lesions, prevented cardiac fibrosis and dysfunction as well as preserved endothelial function. The preservation of EET bioavailability may prevent allograft dysfunction and improve cardiovascular disease in kidney transplant recipients. Inhibition of sEH appears thus as a novel therapeutic option but its impact on other epoxyfatty acids should be carefully evaluated.

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