scholarly journals Whole-Blood Calcineurin Activity Is Not Predicted by Cyclosporine Blood Concentration in Renal Transplant Recipients

2001 ◽  
Vol 47 (9) ◽  
pp. 1679-1687 ◽  
Author(s):  
Raffaele Caruso ◽  
Norberto Perico ◽  
Dario Cattaneo ◽  
Giampiero Piccinini ◽  
Samantha Bonazzola ◽  
...  

Abstract Background: In transplant patients, current cyclosporine (CsA) dose monitoring with classic pharmacokinetics has demonstrated limitations. Evaluation of the activity of calcineurin (CN), the serine-threonine phosphatase enzyme target of CsA, has been proposed as a reliable way to optimize CsA dosing. Methods: CN activity was measured in whole blood in an attempt to overcome the high variability of results obtained previously with peripheral blood mononuclear cells (PBMCs). We also explored, in vitro, a possible relationship between the CsA concentration and CN inhibition in whole blood. Finally, we assessed whether the CsA blood trough concentration correlates with whole-blood CN activity in kidney transplant recipients (n = 15) on maintenance immunosuppression with CsA. Results: In 14 healthy individuals, less scattered CN activity values were documented in whole blood than in the PBMC fraction. Whole-blood CN activity was higher than the sum of the enzyme activity in each cell blood fraction. After ex vivo incubation of whole blood from healthy subjects (n = 5) with increasing concentrations of CsA (50–1000 μg/L for 1 h), a concentration-dependent inhibition of CN activity was found comparable to that in the PBMC fraction. Moreover, in 15 kidney transplant recipients, no relationship was found between CsA pharmacokinetic parameters and CN activity at time 0. However, a highly significant correlation was found between CN area under the CN activity-time curve, which represents the extent of the CN daily inhibition, and CN activity at time 0 (r = 0.79; P <0.01) and at 12 h postdosing (r = 0.96; P <0.01). Conclusions: Measuring CN activity in whole-blood samples is a reproducible method. In kidney transplant recipients, CsA trough concentrations do not predict baseline CN activity. Moreover, a single CN activity monitoring at baseline or at time 12 h post-CsA dosing may be a useful surrogate for the inhibition of this enzyme by CsA during 12 h.

2021 ◽  
Vol 16 ◽  
Author(s):  
Lukas J. Lehner ◽  
Klaus Kalb ◽  
Karl Weigand ◽  
Ulrich Pein ◽  
Peter Schenker ◽  
...  

Background/Objective: Tacrolimus HEXAL®/Crilomus® is an approved generic immunosuppressant for the prevention and treatment of rejection following renal transplantation. For safe and socioeconomically efficient conversion from the innovator to generic formulation, high-quality data are necessary, in view of the different and country-specific comorbidities and pharmacokinetics in kidney transplant recipients. Patients and Methods: From 2014 to 2017, we enrolled 32 kidney transplant recipients, receiving newly prescribed Tacrolimus HEXAL®/Crilomus® in 5 German centers. Efficacy and safety data were collected over 6-8 months and retrospectively compared to the period prior to conversion. Results: The mean tacrolimus trough level was 4.91 ng/mL standard deviation (SD) (SD ±1.7) before and 5.06 ng/mL (SD ±1.97) after conversion. Mean tacrolimus trough concentration-dose-ratio (+/- SD) was 187.1 ng/mL/mg/kg/day (SD 99.2) for the reference and 205.1 ng/mL/mg/kg/day (SD 133) for the generic product, resulting in a non-significant difference of 18.0 ng/mL/mg/kg/day (SD 71.8) (p=0.84, Wilcoxon V=180). Overall, dosing had to be changed in 4 (14.8%) patients. Graft function remained stable and no rejections occurred. Conclusion: In conclusion, conversion to the generic tacrolimus formulation can be considered safe and feasible in long-term kidney transplant recipients in Germany. As suggested by guidelines, a vigilant therapeutic drug monitoring is recommended to account for possible tacrolimus concentration variability on the individual patient level.


2010 ◽  
Vol 90 ◽  
pp. 950
Author(s):  
H. S. CIFTCI ◽  
T. K. AYNA ◽  
Y. Caliskan ◽  
H. TOZKIR ◽  
G. ISITMANGIL ◽  
...  

Nephron ◽  
2020 ◽  
pp. 1-7
Author(s):  
Muhammed Ahmed Elhadedy ◽  
Yazin Marie ◽  
Ahmed Halawa

By April 26, 2020, infections related to coronavirus disease 2019 (COVID-19) affected people from 210 countries and caused 203,818 reported deaths worldwide. A few studies discussed the outcome of COVID-19 in kidney transplant recipients. This short series demonstrates our experience in managing COVID-19 disease in renal transplant patients in the absence of strong evidence. We report 8 cases of kidney transplant recipients infected with COVID-19 (median age = 48.5 years; range = 21–71 years), including 4 males and 4 females. The most frequently associated comorbidity was hypertension. The most common presenting features were fever and cough. The main radiological investigation was a portable chest X-ray. Other common features included lymphopenia, high C-reactive protein, and a very high ferritin level. Overall, 1 patient was managed as an outpatient, the remaining 7 required hospital admission, 1 of them referred to the intensive therapy unit. Management included supportive treatment (intravenous fluid therapy, monitoring renal function, and symptomatic treatment with or without ward-based oxygen therapy depending on oxygen saturation) and discontinuation of the antiproliferative immunosuppressive drugs. Seven patients recovered and discharged home to self-isolate. One patient required intensive care treatment and mechanical ventilation. Supportive treatment could be sufficient for the management or to be tried first. We also found that short hospital stay with self-isolation on discharge reduces the burden on the health service and protect the staff and the public.


2020 ◽  
Vol 78 (7) ◽  
Author(s):  
Angela S Nishikaku ◽  
Marcel V Soldá ◽  
Giannina Ricci ◽  
Vinicius Ponzio ◽  
Carla Pagliari ◽  
...  

ABSTRACT Cryptococcosis is the second most common invasive fungal infection reported in renal transplant recipients. Tissue granulomatous inflammation is necessary to contain Cryptococcus infection. This study aims to analyze the granuloma patterns and in situ expression of regulatory T (Treg) immune response in tissue samples from 12 renal transplant recipients with cryptococcosis. Fungal isolates were molecularly identified as Cryptococcus neoformans species complex. A detailed characterization of granulomas in tissue samples from 12 kidney transplant recipients with cryptococcosis was described by checking six lung and six skin biopsies by conventional histology and for immunohistochemical detection of CD4 and Treg markers: forkhead box P3 (FoxP3), interleukin (IL)-10 and transforming-growth factor (TGF)-β. Granulomas were classified as compact, loose or mixed. Patients with mixed (n = 4) and compact (n = 3) granulomatous inflammation patterns were associated with a better prognosis and presented a higher number of CD4+FoxP3+T cells compared to the group of patients with loose granulomas. In counterpart, three out of five patients with loose granulomas died with cryptococcosis. We suggest that Treg may have a protective role in the tissue response to Cryptococcus infection given its association with compact and mixed granulomas in patients with better clinical outcomes.


2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 21155-21155
Author(s):  
B. E. Beltran ◽  
D. Morales ◽  
M. Medina ◽  
J. Espejo ◽  
R. Castillo ◽  
...  

21155 Background: Malignancy following kidney transplantation is an important medical problem during long-term follow-up. The accrual risk is approximately 100 times greater than the general population. We report some features of the cancers developed in our patient population Methods: We retrospectively reviewed records of 1050 kidney transplant recipients who received both unrelated or related allograft transplants from January 1972 to April 2006 and recorded the incidence of de novo malignancies that developed in this cohort. The study was carried out in two centers in Peru. The statistical method was descriptive and parametrical. Survival was calculated using the Kaplan-Meier method. Results: Forty-six cancer were diagnosed in 42 recipients (4.3%). Twenty six were men and 16 women, mean age was 46.0 years old (range:17–67). Malignancy was diagnosed between 2 to 240 months after transplantation. The tumors included Kaposi's sarcoma (KS) in ten patients, squamous cell carcinoma (SCC) in seven, basal cell carcinoma (BCC) in six, cervix cancer in four, colon and breast cancer in three and hepatocarcinoma in two. Also they were reported one case of small intestine cancer, osteosarcoma, pancreatic cancer, lung cancer, bladder cancer, schwanoma, melanoma, tongue cancer, postransplant lymphoproliferative disease, pelvis renal cancer and carcinomatosis from unknown primary. Thus, KS was the most common malignancy encountered in our series, with a prevalence of 0.95%, followed by SCC observed in 0.66% and BCC found in 0.57% of the patients. The average latency period between transplantation and development of malignancy was 25 months for KS, 72.0 months for SCC and 36.0 months for BCC. KS occurred earlier compared with the other cancers ( P < 0.05); We failed to demonstrate any correlation between age/sex and specific type of cancer. The 10 year - survival was 71%. Conclusions: The prevalence of cancer in our renal transplant recipients was 4.3%. KS and non melanoma skin cancer were the most frequent cancer. Low incidence of postransplant lymphoproliferative disease was found. No significant financial relationships to disclose.


2014 ◽  
Vol 2014 ◽  
pp. 1-9 ◽  
Author(s):  
Brian P. Boerner ◽  
Clifford D. Miles ◽  
Vijay Shivaswamy

New-onset diabetes after transplantation (NODAT) is a common comorbidity after renal transplantation. Though metformin is the first-line agent for the treatment of type 2 diabetes, in renal transplant recipients, metformin is frequently avoided due to concerns about renal dysfunction and risk for lactic acidosis. Therefore, alternative first-line agents for the treatment of NODAT in renal transplant recipients are needed. Sitagliptin, a dipeptidyl-peptidase-4 (DPP-4) inhibitor, has a low incidence of hypoglycemia, is weight neutral, and, in a small study, did not affect immunosuppressant levels. However, long-term sitagliptin use for the treatment of NODAT in kidney transplant recipients has not been studied. We retrospectively analyzed renal transplant recipients diagnosed with NODAT and treated with sitagliptin to assess safety and efficacy. Twenty-two patients were started on sitagliptin alone. After 12 months of followup, 19/22 patients remained on sitagliptin alone with a significant improvement in hemoglobin A1c. Renal function and immunosuppressant levels remained stable. Analysis of long-term followup (32.5±17.8 months) revealed that 17/22 patients remained on sitagliptin (mean hemoglobin A1c < 7%) with 9/17 patients remaining on sitagliptin alone. Transplant-specific adverse events were rare. Sitagliptin appears safe and efficacious for the treatment of NODAT in kidney transplant recipients.


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