Beneficial Effect of Successful Simultaneous Pancreas-Kidney Transplantation on Plasma Profile of Metalloproteinases in Type 1 Diabetes Mellitus Patients

It is not fully elucidated whether the restoring of normal glucose metabolism after successful simultaneous pancreas-kidney transplantation (SPK) improves vascular wall morphology and function in type 1 diabetic (T1D) patients. Therefore, we compared arterial stiffness, assessed by pulse wave velocity (PWV), carotid intima-media thickness (IMT), and biomarkers of arterial wall calcification in T1D patients after SPK or kidney transplantation alone (KTA). In 39 SPK and 39 KTA adult patients of similar age, PWV, IMT, circulating matrix metalloproteinases (MMPs) and calcification biomarkers were assessed at median 83 months post transplantation. Additionally, carotid plaques were visualized and semi-qualitatively classified. Although PWV and IMT values were similar, the occurrence of atherosclerotic plaques (51.3 vs. 70.3%, p < 0.01) and calcified lesions (35.9 vs. 64.9%, p < 0.05) was lower in SPK patients. There were significantly lower concentrations of MMP-1, MMP-2, MMP-3, and osteocalcin in SPK subjects. Among the analyzed biomarkers, only logMMP-1, logMMP-2, and logMMP-3 concentrations were associated with log HbA1c. Multivariate stepwise backward regression analysis revealed that MMP-1 and MMP-3 variability were explained only by log HbA1c. Normal glucose metabolism achieved by SPK is followed by the favorable profile of circulating matrix metalloproteinases, which may reflect the vasoprotective effect of pancreas transplantation.

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Beneficial effect of successful simultaneous pancreas-kidney transplantation on plasma profile of metalloproteinases in type 1 diabetes mellitus patients

10.21203/rs.3.rs-42379/v1 ◽

2020 ◽

Author(s):

Jerzy Chudek ◽

Aureliusz Kolonko ◽

Jacek Ziaja ◽

Tomasz Francuz ◽

Dorota Kamińska ◽

...

Keyword(s):

Kidney Transplantation ◽

Calcium Phosphate ◽

Glucose Metabolism ◽

Phosphate Metabolism ◽

Normal Glucose ◽

Pancreas Kidney Transplantation ◽

Simultaneous Pancreas Kidney ◽

Calcium Phosphate Metabolism ◽

Simultaneous Pancreas Kidney Transplantation

Abstract Background It is virtually unknown whether the restoring of normal glucose metabolism after successful simultaneous pancreas-kidney transplantation (SPK) improves vascular wall morphology and function in type 1 diabetic (T1D) patients. This study has been aimed to compare arterial stiffness, assessed by pulse wave velocity (PWV), carotid intima-media thickness (IMT) biomarkers of arterial wall calcification, and parameters of calcium-phosphate metabolism in T1D patients after SPK or kidney transplantation alone (KTA). Methods In 39 SPK and 39 KTA adult patients of similar age, PWV and IMT were measured at a median of 83 (62–109) months post-transplantation. Additionally, carotid plaques were visualized and semi-qualitatively classified. Circulating matrix metalloproteinases (MMPs), calcification biomarkers, and calcium-phosphate metabolism parameters were measured. Results Although PWV and IMT values were similar, the occurrence of atherosclerotic plaques (51.3 vs. 70.3%, p < 0.01), turned to be lower, especially in case of calcified lesions (35.9 vs. 64.9%, p < 0.05) in patients after SPK. There were significantly lower concentrations of MMP-1, MMP-2, MMP-3 and osteocalcin (OC) in SPK subjects. Among the analyzed biomarkers, only log MMP-1, log MMP-2 and log MMP-3 concentrations were associated with log HbA1c. In addition, both log MMP-1 and log MMP-3 were inversely related to estimated glomerular filtration rate (eGFR). Multivariate stepwise backward regression analysis revealed that MMP-1 and MMP-3 variability were explained only by log HbA1c, whereas OC variability only by eGFR. Conclusion Normal glucose metabolism achieved by simultaneously transplanted pancreas in T1D renal transplant recipients is followed by the favorable profile of circulating matrix metalloproteinases, which may reflect the vasoprotective effect of SPK.

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Simultaneous pancreas-kidney transplantation: Pro et Contra

Diabetes Mellitus ◽

10.14341/2072-0351-5814 ◽

2011 ◽

Vol 14 (4) ◽

pp. 32-37

Author(s):

Alexandra Mikhailovna Glazunova ◽

Malkhaz Viktorovich Kvaratskheliya ◽

Minara Shamkhalovna Shamkhalova ◽

Marina Vladimirovna Shestakova

Keyword(s):

Kidney Transplantation ◽

Glycated Hemoglobin ◽

Post Transplantation ◽

Artery Disease ◽

Pancreas Kidney Transplantation ◽

Transplantation Complications ◽

Simultaneous Pancreas Kidney ◽

Simultaneous Pancreas Kidney Transplantation ◽

Coronary Artery Disease Progression

The review addresses the questions of history, clinical features and outcomes of simultaneous pancreas-kidney transplantation in patients with diabetesmellitus type 1. This approach was shown to have positive aspects, such as improvement of glycemic control, rapid normalization and long-termmaintenance of glycated hemoglobin levels, disappearance of hypoglycemic events, and deceleration of coronary artery disease progression resultedin reduced incidence of cardiovascular mortality. Operative risk and post-transplantation complications are also described in details.

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A Valine Mismatch at Position 129 of MICA Is an Independent Predictor of Cytomegalovirus Infection and Acute Kidney Rejection in Simultaneous Pancreas–Kidney Transplantation Recipients

International Journal of Molecular Sciences ◽

10.3390/ijms19092618 ◽

2018 ◽

Vol 19 (9) ◽

pp. 2618 ◽

Cited By ~ 1

Author(s):

Rafael Michita ◽

José Chies ◽

Sabine Schramm ◽

Peter Horn ◽

Falko Heinemann ◽

...

Keyword(s):

Kidney Transplantation ◽

Natural Killer ◽

Cytomegalovirus Infection ◽

Independent Predictor ◽

Soluble Form ◽

First Year ◽

Post Transplantation ◽

Pancreas Kidney Transplantation ◽

Simultaneous Pancreas Kidney ◽

Simultaneous Pancreas Kidney Transplantation

The polymorphic major histocompatibility complex class I chain-related molecule A (MICA) and its soluble form (sMICA) interact with activating receptor natural-killer group 2 member D (NKG2D) on natural-killer (NK) and T cells, thereby modifying immune responses to transplantation and infectious agents (e.g., cytomegalovirus). Two single-nucleotide polymorphisms (SNPs), rs2596538GA in the MICA promoter and rs1051792AG in the coding region (MICA-129Val/Met), influence MICA expression or binding to NKG2D, with MICA-129Met molecules showing higher receptor affinity. To investigate the impact of these SNPs on the occurrence of cytomegalovirus infection or acute rejection (AR) in individuals who underwent simultaneous pancreas–kidney transplantation (SPKT), 50 recipient-donor pairs were genotyped, and sMICA levels were measured during the first year post-transplantation. Recipients with a Val-mismatch (recipient Met/Met and donor Val/Met or Val/Val) showed shorter cytomegalovirus infection-free and shorter kidney AR-free survival. Additionally, Val mismatch was an independent predictor of cytomegalovirus infection and kidney AR in the first year post-transplantation. Interestingly, sMICA levels were lower in rs2596538AA and MICA129Met/Met-homozygous recipients. These results provide further evidence that genetic variants of MICA influence sMICA levels, and that Val mismatch at position 129 increases cytomegalovirus infection and kidney AR risk during the first year post-SPKT.

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