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Use of a calcineurin inhibitor (CNI) immunosuppressant following kidney transplantation is associated with development of vasomotor nephrotoxicity. This study was undertaken to evaluate and compare the influences of CNI-based and CNI-free immunosuppressant regimens on two intrarenal vascular resistance parameters, the resistive index (RI) and the p...
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Citations
... Determination of the RI is a useful tool in assessing the prognosis for graft survival in the chronic period after transplantation, because it reflects the vascular status of the allograft (23)(24)(25)(26) . An RI > 0.8 are usually typical of allograft malfunction and death with a functioning graft (27) . Ba et al. (24) found that an increase > 1 in the RI could reflect absence of end-diastolic blood flow, resulting in a worse prognosis for renal allograft survival. ...
Objective:
To evaluate the association between shear wave elastography parameters and arterial resistance in kidney transplant recipients.
Materials and methods:
This was a prospective cross-sectional study involving consecutive adult kidney transplant recipients. All patients underwent color Doppler to evaluate the resistive index (RI) and ultrasound shear wave elastography for the quantification of renal allograft stiffness.
Results:
We evaluated 55 patients, of whom 9 (16.4%) had an RI defined as abnormal (≥ 0.79) and 46 (83.6%) had an RI defined as normal (< 0.79). The mean age was higher in the abnormal RI group than in the normal RI group (68.0 ± 8.6 years vs. 42.6 ± 14.1 years; p < 0.001), as was the mean shear wave velocity (2.6 ± 0.4 m/s vs. 2.2 ± 0.4 m/s; p = 0.013). Multivariate analysis identified two independent predictors of arterial resistance: age (OR = 1.169; 95% CI: 1.056 to 1.294; p = 0.003) and shear wave velocity (OR = 17.1; 95% CI: 1.137 to 257.83; p = 0.040).
Conclusion:
We observed an association between rigidity in the cortex of the transplanted kidney, as evaluated by shear wave elastography, and arterial resistance, as evaluated by color Doppler, in kidney transplant recipients.
... The latter may result in vasoconstriction and relative ischemia of macular optic fibers [12]. Interestingly, the vasoconstrictive effect of tacrolimus on renal microcirculation is mediated by a nitric oxide blockade [22] and causes a higher intrarenal resistance index (RI) measured by Doppler ultrasound as compared with m-TOR inhibitor immunosuppressive regimen [23]. Moreover, in patients with unilateral optic neuritis confirmed by pathological VEP results, unilateral changes in orbital hemodynamics were found, including the asymmetrically increased RI values [24,25]. ...
In kidney transplant recipients (KTRs), uraemia-induced central nervous system damage partly subsides, while the long-lasting exposure to tacrolimus may cause pathologic visual evoked potentials (VEP) findings, which have not been investigated yet. Thus, the aim of the present study was to assess the effect of tacrolimus maintenance treatment on bioelectrical function of optic nerves in stable KTRs. Sixty-five stable KTRs were enrolled, including 30 patients treated with twice-daily (Prograf) and 35 patients treated with prolonged once-daily (Advagraf) tacrolimus formulation. In all patients, pattern and flash VEP measurements were performed. Tacrolimus dosing and exposure were also analyzed. Overall, 129 eyes were analyzed. In pattern VEP, both (1°) and (15′) latencies of P100 waves were significantly longer, whereas (1°) and (15′) amplitudes were lower in the Advagraf group as compared with the Prograf group. Multivariate regression analyses revealed that the use of Advagraf (vs. Prograf) was independently associated with longer (1°) and (15′) P100 latencies and lower corresponding amplitudes, whereas log tacrolimus daily dose was only related to amplitudes in a whole study group. In flash VEP, log tacrolimus trough level was associated with negative changes in P2 wave amplitude irrespective of tacrolimus formulation, whereas its association with P2 latency was observed only in the Prograf group. Both the type of tacrolimus formulation and drug exposure influenced the VEP parameters in stable KTRs.
... It has been indicated that RI in the early post-transplantation period is correlated with long-term transplant function [19]. RI values higher than 0.8 were linked to allograft dysfunction [20]. But RI has recently been regarded as inapplicable for the diagnosis of renal allograft dysfunction due to the lack of discriminatory power [21]. ...
Background:
Renal transplantation is the treatment of choice in end-stage renal disease. Chronic allograft dysfunction is the leading cause of chronic allograft failure. Surveillance biopsy is the only reliable tool to detect early fibrosis in the allograft. There is a need for non-invasive methods for the detection of early development of renal allograft fibrosis.
Aims:
To analyze the reliability of sonographic elasticity index and resistive index measurements in the evaluation of renal transplant fibrosis using linear and convex transducers according to segmental anatomy.
Materials and methods:
Elasticity index and resistive index were measured in 28 renal transplants and correlated with clinical prognostic parameters. Donor age above 50 years old, post transplantation time over 60 months and serum creatinine level above 1.5 mg/dl were defined as poor prognostic parameters.
Results:
Renal transplant recipients with serum creatinine level above 1.5 mg/dl demonstrated higher mean elasticity index (p=0.006) with a convex probe and higher elasticity index in the middle segments both with a convex and a matrix linear probe (p=0.026, p=0.001). Renal transplant recipients with post-transplantation time of 60 months and more demonstrated higher resistive index values in the middle segments (p=0.016).
Conclusions:
Convex probe was able to detect the changes in mean stiffness better than the matrix linear probe. The measurements from subsegments might suggest that diffuse changes in stiffness can truly be detected in the middle segments or that fibrotic processes start from the middle segments of the renal transplants. Further studies correlated with histopathology are required to validate the findings.
... The safety of the immunosuppressive protocol was assessed by monitoring the frequency, severity, duration and relation with the study drug of adverse events throughout the study period, including episodes of serious infection, immunosuppressionrelated complications and deviations from the study protocol for any reason. Laboratory tests, including hematology, biochemistry and urinalysis, were performed at preconversion and 0, 2,4,8,12,20,28,36,44, and 52 weeks after conversion. Protocol biopsies were performed at the screening point and 1 yr after conversion. ...
... However, the continuous administration of CNI is associated with chronic vascular and tubulointerstitial lesions, which can cause irreversible nephropathy (26,27). Therefore, the beneficial effect of early CNI withdrawal and SRL conversion is at least partially due to a decrease in intrarenal vascular resistance parameters (28). A functional improvement in SRL conversion patients who were exposed to CNI less than 1 yr was observed, but no histological improvement was observed. ...
This study was designed to evaluate whether sirolimus (SRL) conversion effectively improves renal function and histopathology in calcineurin inhibitor (CNI)-treated renal recipients with mild to moderate renal insufficiency. SRL conversion from CNI was performed in patients who underwent kidney transplantation from 6 months to 5 yr prior to screening. Forty-five patients were enrolled. The effect of SRL conversion on graft function was evaluated, and protocol biopsies were performed preconversion and 1 yr after conversion. Overall graft function after SRL conversion gradually improved, and the improvement in renal function was closely associated with the shorter duration of CNI exposure. When we divided the patients by the duration of CNI exposure, the patients with less than 1 yr of CNI exposure demonstrated significant improvement, but patients with a greater than 1 yr CNI exposure did not exhibit significant improvement. In contrast, protocol biopsies demonstrated no significant improvements in the modified "ah" score or other Banff scores after SRL conversion. Furthermore, the duration of CNI treatment prior to SRL conversion was not associated with histological findings 1 yr after SRL conversion. SRL conversion improved graft function in renal recipients with mild to moderate renal insufficiency, but this effect is not accompanied by histological improvement.
Graphical Abstract
... In addition, sonoelastography has also wide range intra-and low interobserver agreement in renal transplants. The RI and PI have been used as indicators for assessing the hemodynamics of renal transplants (Lee et al. 2010; Gao et al. 2011; McArthur et al. 2011). Cutoff values of RI .0.8 and of PI .1.8 ...
... Cutoff values of RI .0.8 and of PI .1.8 are usually typical of both allograft malfunction and death with a functioning graft (Lee et al. 2010). In a recent study, McArthur et al. (2011) have stated that PI and RI in the early post-transplantation period correlated with long-term transplant function and can possible be used as prognostic indicators to aid risk stratification for future transplant dysfunction. ...
Real-time sonoelastography (RSE) is a relatively new imaging technique that visualizes relative difference in tissue hardness by evaluating changes in local strain in response to external stress. Our aim was to evaluate the ability of investigators to use sonoelastography to detect differences in renal cortical stiffness and assess the relationship between stiffness and clinical-Doppler parameters. In 42 adult renal transplant recipients, sonoelastography of kidney was performed to calculate the strain ratio (SR) of the central echo complex to the renal parenchyma. Resistive index (RI) and pulsatility index (PI) were also measured. Estimated glomerular filtration rate (eGFR) was calculated. Parenchymal stiffness showed significant positive correlation with RI and PI (r: 0.41 p = 0.007 and r: 0.48 p = 0.001, respectively). Parenchymal stiffness and eGFR did not have a significant correlation (p = 0.42). Interobserver agreement, expressed as intraclass correlation coeffiicient was 0.47 (95% CI: 0.05-0.70). Parenchymal stiffness (SR) showed significant positive correlation with RI and PI but sonoelastography has also wide range intra- and low interobserver agreement in renal transplants. Further studies are warranted in larger patient groups to determine the reliability of sonoelastography in renal transplants.
Background
Renal Doppler ultrasound intrarenal resistive index (RI) and pulsatility index (PI) are 2 noninvasive Doppler ultrasonographic markers to determine kidney allograft function, and have been used mainly for diagnosing allograft dysfunction during early posttransplantation periods. Little is known about the stability of RI and PI in allograft recipients receiving cyclosporine A (CyA)-, tacrolimus (TAC)-, or sirolimus (SRL)-based immunosuppressive regimens long-term after kidney transplantation.
Methods
This study assessed RI and PI by Doppler ultrasonography in 155 kidney allograft recipients between July 2012 and March 2013. The period from kidney transplantation to performance of allograft Doppler ultrasound was between 23 and 231 months in the TAC group (n = 75), 21 and 261 months in the CyA group (n = 25), and 21 and 210 months in the SRL group (n = 55).
Results
Univariate logistic regression analysis revealed no correlation between resistance indexes and estimated glomerular filtration rate, proteinuria, cholesterol, triglyceride, graft and patient survival, human leukocyte antigen mismatches, and creatinine. There was no significant difference among the TAC, CyA, and SRL treatment groups in terms of resistance indexes (RI and PI) (P = .193 and P = .216, respectively). Univariate logistic regression analysis revealed that RI and PI values correlated significantly with the recipients' ages (R = 0.375, P < .001), but not with donor age. The results of multivariate logistic regression analysis also revealed statistically the strongest correlation between recipients' ages and RI (95% confidence interval = 0.002, R² = 20.5%, P < .001) and PI (95% confidence interval = 0.008, R² = 16.2%, P < .001) values.
Conclusions
Intrarenal RI and PI remained stable over time in allograft recipients after transplantation, and there was no significant difference between calcineurin inhibitor-based and calcineurin inhibitor-free immunosuppressive treatment groups. Only recipients' ages showed a positive correlation with RI and PI values. Long-term allograft and patient survival were both excellent (100%) and associated with RI < 0.75.
Clinical evidence on the use of anti-mTOR drugs in renal transplantation ABSTRACT The calcineurin inhibitor drugs (CNI) are the mainstays of modern immunosuppression in renal transplantation, but they contribute significantly to the chronic graft loss and the high morbidity and mortality in this population for their deleterious effects on renal graft, cardiovascular profile and malignancies. The anti-mTOR drugs, sirolimus (SRL) and everolimus (EVE), are potent immunosuppressants with anti-proliferative and anti-migration properties. This confers them a potential protective role in graft dysfunction, the optimization of renal function and the appearance of malignancies. Indeed, clinical trials and observational studies have demonstrated that conversion from CNI to anti-mTOR-based maintanace therapy has beneficial effects on transplant outcomes in terms of renal function, without significant increase in acute rejection rates. In this review, we analyze the evidence of the use of anti-mTOR in the following clinical situations following renal transplantation: 1) Prevention of immune dysfunction and renal function preservation in de novo kidney transplantation and after early or late CNI withdrawal; 2) Chronic graft dysfunction, 3) Cardiovascular complications, 4) Diabetes de novo posttransplantation; and 5) De novo malignancies.
Calcineurin inhibitor drugs (CNI) are the mainstay of modern immunosuppression in renal transplantation. However, they contribute significantly to the chronic loss of renal grafts and the high morbidity and mortality in this population due to their deleterious effects on the renal graft, cardiovascular profile and tumour pathology. Anti-mTOR drugs, sirolimus (SRL) and everolimus (EVE) are potent immunosuppressants with antiproliferative and anti-migratory capacities. These properties mean that they have a potential protective role in graft dysfunction, in renal function optimisation and the appearance of malignant tumours. Indeed, clinical trials and observational studies have demonstrated that conversion from CNI to anti-mTOR-based maintenance therapy has beneficial effects on transplant outcomes in terms of renal function, without significant increase in acute rejection rates. This review article examines the evidence of the use of anti-mTOR in the following clinical situations following renal transplantation: 1) prevention of immune dysfunction and renal function preservation in de novo renal transplantation and after early or late CNI withdrawal; 2) chronic dysfunction of the renal graft; 3) cardiovascular effects; 4) de novo post-transplant diabetes, and 5) de novo tumour pathology.
