scholarly journals Impact of Genetic Polymorphisms at the Promoter area of IL-10 Gene on Tacrolimus Level in Jordanian Renal Transplantation Recipients

2021 ◽  
Author(s):  
Bara’ah Khaleel ◽  
Al-Motassem Yousef ◽  
Mazhar AL-Zoubi ◽  
Muhammad AL-Ulemat ◽  
Ahmad Masadeh ◽  
...  
Keyword(s):  
Kidney Transplantation ◽  
Drug Disposition ◽  
Transplant Rejection ◽  
Interleukin 10 ◽  
Blood Levels ◽  
Solid Organ ◽  
Nucleotide Polymorphisms ◽  
Kidney Transplant Recipients ◽  
Post Transplantation ◽  
The Impact

Background Tacrolimus is a widely used immunosuppressant that prevents the solid organ transplant rejection. The pharmacokinetics of Tacrolimus show considerable variability. interleukin-10 (IL-10), in the host’s immune response after transplantation contributes to the variable CYP3A-dependent drug disposition of Tacrolimus. In current study, our aim is to evaluate the impact of single nucleotide polymorphisms (SNP) in the promoter region of of IL-10 on Tacrolimus dose requirements and the Dose Adjusted Concentration (DAC) of Tacrolimus among kidney transplantation recipients.  Methods Blood levels of Tacrolimus were measured using Micorparticle Enzyme Immunoassay (MEIA) for six months post-transplantation. Genotyping analysis was utilized using specific Polymerase Chain Reaction (PCR) followed by sequencing methods for 98 Jordanian kidney transplant recipients. Results Genotyping frequencies of IL-10 (-592) were (CC/CA/AA: 38, 46.7, 15.2%); IL-10 (-819) were (CC/CT/TT: 40.4, 44.1, 15.1%); and IL-10 (-1082) were (AA/AG/GG: 42.6, 44.7, 12.8%). The impact of IL-10 (-1082) on Tacrolimus DAC was gender dependent. Men carrying at least one A allele had significantly lower DAC than men carrying GG genotyping only in the first month post-transplantation [88.2±32.1 vs. 117.5±22.5 ng/ml per mg/kg/day, p=0.04].. Conclusion Our current study showed that the interaction between gender and IL-10 -1082 affects Tacrolimus DAC in Jordanian kidney transplantation recipients during the first month post-transplantation.

scholarly journals B-cell activating factor BAFF as a novel alert marker for the immunological risk stratification after kidney transplantation

2021 ◽  
Author(s):  
Antonia Margarete Schuster ◽  
N. Miesgang ◽  
L. Steines ◽  
C. Bach ◽  
B. Banas ◽  
...  
Keyword(s):  
Kidney Transplantation ◽  
B Cell ◽  
Graft Function ◽  
Risk Profile ◽  
Kidney Transplant Recipients ◽  
Post Transplantation ◽  
Antibody Mediated Rejection ◽  
B Cell Activating Factor ◽  
Medium Risk ◽  
Patients At Risk

AbstractThe B cell activating factor BAFF has gained importance in the context of kidney transplantation due to its role in B cell survival. Studies have shown that BAFF correlates with an increased incidence of antibody-mediated rejection and the development of donor-specific antibodies. In this study, we analyzed a defined cohort of kidney transplant recipients who were treated with standardized immunosuppressive regimens according to their immunological risk profile. The aim was to add BAFF as an awareness marker in the course after transplantation to consider patient’s individual immunological risk profile. Included patients were transplanted between 2016 and 2018. Baseline data, graft function, the occurrence of rejection episodes, signs of microvascular infiltration, and DSA kinetics were recorded over 3 years. BAFF levels were determined 14 d, 3 and 12 months post transplantation. Although no difference in graft function could be observed, medium-risk patients showed a clear dynamic in their BAFF levels with low levels shortly after transplantation and an increase in values of 123% over the course of 1 year. Patients with high BAFF values were more susceptible to rejection, especially antibody-mediated rejection and displayed intensified microvascular inflammation; the combination of high BAFF + DSA puts patients at risk. The changing BAFF kinetics of the medium risk group as well as the increased occurrence of rejections at high BAFF values enables BAFF to be seen as an awareness factor. To compensate the changing immunological risk, a switch from a weaker induction therapy to an intensified maintenance therapy is required.

scholarly journals The EKiTE network (epidemiology in kidney transplantation - a European validated database): an initiative epidemiological and translational European collaborative research

2019 ◽  
Vol 20 (1) ◽  
Author(s):  
M. Lorent ◽  
◽  
Y. Foucher ◽  
K. Kerleau ◽  
S. Brouard ◽  
...  
Keyword(s):  
Kidney Transplantation ◽  
Clinical Epidemiology ◽  
Main Body ◽  
Large Set ◽  
Kidney Transplant Recipients ◽  
Clinical Practices ◽  
Post Transplantation ◽  
Wide Range ◽  
Epidemiology Studies ◽  
Transplantation Outcomes

Abstract Background Kidney transplantation is considered to be the treatment of choice for people with end-stage renal disease (ESRD). However, due to the shortage of available organs and the increase in the ESRD prevalence in Europe, it is essential to improve transplantation outcomes by studying the related prognostic factors. Today, there is no European registry collecting data to perform such clinical epidemiology studies. Main body Entitled EKiTE, for European cohort for Kidney Transplantation Epidemiology, this prospective and multicentric cohort includes patients from Spanish (Barcelona), Belgian (Leuven), Norwegian (Oslo) and French (Paris Necker, Lyon, Nantes, Nancy, Montpellier, Nice and Paris Saint Louis) transplantation centers and currently contains 13,394 adult recipients of kidney (only) transplantation from 2005 and updated annually. A large set of parameters collected from transplantation until graft failure or death with numbers of post-transplantation outcomes. The long-term follow-up and the collected data enable a wide range of possible survival and longitudinal analyses. Conclusion EKiTE is a multicentric cohort aiming to better assess the natural history of the ESRD in European kidney transplant recipients and perform benchmarking of clinical practices. The data are available for clinical epidemiology studies and open for external investigators upon request to the scientific council. Short-term perspectives are to extend EKITE network to other European countries and collect additional parameters in respect of the common thesaurus.

scholarly journals Donor genetic variants in interleukin-6 and interleukin-6 receptor associate with biopsy-proven rejection following kidney transplantation.

2021 ◽  
Author(s):  
Felix Poppelaars ◽  
Mariana Gaya da Costa ◽  
Siawosh K. Eskandari ◽  
Jeffrey Damman ◽  
Marc A. Seelen
Keyword(s):  
Kidney Transplantation ◽  
Renal Transplantation ◽  
Renal Transplant ◽  
Interleukin 6 ◽  
Medical Center ◽  
Organ Donors ◽  
Nucleotide Polymorphisms ◽  
Increased Risk ◽  
Major Player ◽  
The Impact

Rejection after kidney transplantation remains an important cause of allograft failure that markedly impacts morbidity. Cytokines are a major player in rejection, and we, therefore, explored the impact of interleukin-6 (IL6) and IL-6 receptor (IL6R) gene polymorphisms on the occurrence of rejection after renal transplantation. We performed an observational cohort study analyzing both donor and recipient DNA in 1,271 renal transplant-pairs from the University Medical Center Groningen in The Netherlands and associated single nucleotide polymorphisms (SNPs) with biopsy-proven rejection after kidney transplantation. The C-allele of the IL6R SNP (Asp358Ala: rs2228145 A>C, formerly rs8192284) in donor kidneys conferred a reduced risk of rejection following renal transplantation (HR 0.78 per C-allele; 95%-CI 0.67-0.90; P=0.001). On the other hand, the C-allele of the IL6 SNP (at position-174 in the promoter; rs1800795 G>C) in donor kidneys was associated with an increased risk of rejection for male organ donors (HR per C-allele 1.31; 95%-CI 1.08-1.58; P=0.0006), but not female organ donors (P=0.33). In contrast, neither the IL6 nor IL6R SNP in the recipient showed an association with renal transplant rejection. In conclusion, donor IL6 and IL6R genotypes but not recipient genotypes represent an independent prognostic marker for biopsy-proven renal allograft rejection.

scholarly journals Impacts of Interleukin-18 Polymorphisms on the Incidence of Delayed-Onset Cytomegalovirus Infection in a Cohort of Kidney Transplant Recipients

2019 ◽  
Vol 6 (9) ◽  
Author(s):  
Isabel Pérez-Flores ◽  
Jose Luis Santiago ◽  
Cristina Fernández-Pérez ◽  
Elena Urcelay ◽  
María Ángeles Moreno de la Higuera ◽  
...  
Keyword(s):  
Kidney Transplant ◽  
Cytomegalovirus Infection ◽  
Disease Incidence ◽  
Defense Responses ◽  
Solid Organ ◽  
Nucleotide Polymorphisms ◽  
Transplant Recipients ◽  
Kidney Transplant Recipients ◽  
Cmv Infection ◽  
Delayed Onset

Abstract Background The incidence of cytomegalovirus (CMV) infection in solid organ transplant recipients may be reduced by antiviral prophylaxis, but this strategy may lead to delayed-onset CMV infection. The proinflammatory cytokine interleukin (IL)-18 plays a major role in viral host defense responses. This study examines the impacts of 2 single-nucleotide polymorphisms (SNPs) in the promoter region of the IL-18 gene, -607C/A (rs1946518) and -137G/C (rs187238), on the incidence of delayed-onset CMV infection in patients undergoing kidney transplant. Methods This retrospective study analyzed 2 IL-18 SNPs in consecutive adult kidney transplant recipients using real-time polymerase chain reaction with TaqMan probes. Participants were enrolled over the period 2005–2013 and stratified according to their IL-18 SNP genotype. The concordance index (Harrell’s c-index) was used as a measure of the discriminatory power of the predictive models constructed with bootstrapping to correct for optimistic bias. Results Seven hundred nine patients received transplants in the study period, and 498 met selection criteria. Cytomegalovirus infection and disease incidence were 38% and 7.5%, respectively. In multivariate competing risk regression models, carriers of the -607C/-137G haplotype who received prophylaxis showed a higher incidence of CMV replication after antiviral agent discontinuation (hazard ratio = 2.42 [95% confidence interval, 1.11–5.26]; P = .026), whereas CMV disease was not observed in those given prophylaxis who were noncarriers of this polymorphism (P = .009). Conclusions Our findings suggest that the -607C/-137G IL-18 haplotype is associated with a higher incidence of postprophylaxis CMV replication. The prior identification of this polymorphism could help select alternative measures to prevent delayed-onset CMV infection in these patients.

Interleukin-10(IL-10)1082-A and Tumor Necrosis Factor(TNF)-Alpha 238/308A Genotypes Are Associated with Earlier (Younger Than 55) Onset of Multiple Myeloma.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 4869-4869
Author(s):  
Meral Beksac ◽  
Merih Kizil ◽  
Ender A. Soydan ◽  
Esin Serbest ◽  
Klara Dalva
Keyword(s):  
Age Of Onset ◽  
Interleukin 10 ◽  
Tnf Alpha ◽  
Nucleotide Polymorphisms ◽  
Promoter Gene ◽  
Age Of Diagnosis ◽  
Definition Of ◽  
The Individual ◽  
The Impact ◽  
Secretory Pattern

Abstract The individual differences among the polymorphic regions of the cytokine genes involved in the pathogenesis of myeloma have been investigated by various groups: Neben et al have found the TNF238 A allel to be associated with a higher serum level of TNF-alpha and with better response to Thalidomide. The IL 10-1082 G promoter gene genotype have been found to be associated with high secretory pattern and in increased frequency among myeloma patients compared to normal controls by Zheng et al. Van Ness et al have reported the IL-10-G genotype to be associated with shorter survival compared to IL-10-A allele carriers None of these groups have analyzed the impact of these genotypes on age of onset. With an aim to analyze the association between the frequencies of the cytokines known to be important in the pathogenesis of Myeloma, TNF-alpha, IL-6, IL-10 and the age of diagnosis, we have isolated DNA from peripheral blood of 59 patients. Patients with a median age of 56(28–83)M/F:35/24 diagnosed and treated in our center between 2002–2004 were analyzed. To determine the TNF 238 and 308(G/A), IL-6 174(G/C), IL-10 1082(G/A),819(T/C) and 592(A/C) bp polymorphic allele frequencies Cytokine Genotyping Kit (Pel-Freeze) and/or Cytgen (OneLambda) Genotyping Trays have been used. Evaluation of results were done as described in the worksheets. Interpretation and definition of phenotypes(low and high secretory patterns) were based on the previously published reports. 30 patients(50,8%) were younger than 56 (median=the cutoff:56). TNF-A homozygous alelle couldnot be observed among all patients. The frequencies of all alleles were: TNF-alfa308A, TNF-alfa238A, IL-10 1082 G 20%, 20%, 12% respectively. IL-6 -GG/GC alleles which have been linked with high secretory pattern constituted the majority of the patients(58/59). When TNFalfa-A were detected based on the 238 bp reactivity the association of low phenotype with elder age was remarkable(p=0.019). This finding wasnot valid for the 308 bp location. IL-10 phenotypes were more complicated with an accumulation in the intermediate level of secretion. The impact of TNF was varified with the separate evaluation of this group, based on their TNF-238/308 genotype, p=0.031). Conclusion: There is a trend towards younger age of onset in Myeloma. Genetic factors for susceptibility have not been defined yet. The new tools for detection of single nucleotide polymorphisms have a promising role in this field. In our prospective study we have found a predominance of low IL-10 secretory A genotype and the high secretory TNF-A genotype among patients younger than 56. To our knowledge this is the first report on such an association. Investigation of other genes in linkeage with TNF on the neighboring MHC region may be necessary for understanding myeloma pathogenesis. Age TNF 238 H/L TNF 308 H/L TNF 238,308 H/L IL-10 H/I/L IL-10 I,TNF H(238 or 308)/ IL-10 I,TNF L(238 or308) L:Low, H: High,I:Intermediate secretory, TNF238A:H, TNF238G:L, TNF308A:H, TNF308G:L, IL-10G: H ≤55 5 / 7 6 / 24 7 / 5 1 /16 / 13 5 / 2 >55 1 / 16 6 / 23 4 / 13 6 /13 / 8 1 / 6 N=29, p=0.019 N=59, p=0.948 N=29, p=0.057 N=57, p=0.085 N=14, p=0.031

scholarly journals Post-transplant monitoring of lymphocyte counts predict the occurrence of CMV infection in early phase of kidney transplantation

2020 ◽  
Author(s):  
Sujuan Feng ◽  
Jing Yang ◽  
Xiaodong Zhang
Keyword(s):  
Kidney Transplantation ◽  
Peripheral Blood ◽  
Operating Characteristic ◽  
Roc Curves ◽  
Transplant Recipients ◽  
Kidney Transplant Recipients ◽  
Cmv Infection ◽  
Post Transplantation ◽  
Cmv Dnaemia

Abstract Objectives The aim of this study was to assess whether monitoring of the number of lymphocytes in peripheral blood was helpful for evaluating the risk of cytomegalovirus (CMV) infection after kidney transplantation. Methods The total numbers of lymphocyte in peripheral blood were measured at baseline and posttransplant months 1, 3 and 6. Risk factors for DNAemia in KTRs were analyzed using univariate logistic regression analyses. Areas under receiver operating characteristic (ROC) curves were applied to assess the accuracy of lymphocyte counts for predicting CMV DNAemia. Results After follow-up 6 months, CMV replication was detected in 12 (31.6%) kidney transplant recipients (KTRs). The total lymphocyte counts were significantly decreased in KTRs with CMV DNAemia in 1, 3 and 6 months. There was a negative correlation between CMV copies and the lymphocyte counts in 1, 3 and 6 months post-transplantation, and the decrease of lymphocyte counts in the 6 months post-transplantation was the risk factor of CMV DNAemia in the KTR. Patients with lymphocyte counts 1.085×109 cells/L had higher cumulative incidence of CMV infection.Conclusions The lymphocyte counts post kidney transplantation may be used as a simple and effective indicator for monitoring the CMV infection status in KTR and for predicting the risk of CMV DNAemia.

scholarly journals 210. Outcomes of Kidney Transplant Recipients with Donor Positive Blood Cultures

2021 ◽  
Vol 8 (Supplement_1) ◽  
pp. S213-S214
Author(s):  
Petros Svoronos ◽  
Prakhar Vijayvargiya ◽  
Pradeep Vaitla ◽  
James j Wynn ◽  
Elena Beam ◽  
...  
Keyword(s):  
Blood Culture ◽  
Kidney Transplant ◽  
Demographic Data ◽  
Blood Cultures ◽  
Solid Organ ◽  
Transplant Recipients ◽  
Kidney Transplant Recipients ◽  
Donor Blood ◽  
Post Transplantation ◽  
Duration Of Therapy

Abstract Background Based on expert opinion, solid organ transplant recipients from donors with bacteremia are treated with 7-14 days of pre-emptive antibiotic therapy (PAT). However, studies addressing necessity, optimal duration of therapy, and outcomes in kidney transplant recipients (KTR) are lacking. Methods We retrospectively reviewed all kidney transplants performed at our institution from 01/01/2015-01/01/2021 to identify those cases where matched deceased donors had positive blood cultures. Bacteremia was defined per CDC criteria. We analyzed rate of infection in the KTR with the same organism identified in the donor blood culture within 30 days of transplantation. Results A total of 56 KTRs with donor positive blood cultures were identified. Demographic data are summarized in Table 1. Twenty of 56 cases (35.8%) had bacteremia and 36 (64.2%) had organisms classified as common commensals. The most common organisms in the bacteremia group were Gram-negative bacteria (12/20) and Staphylococcus aureus (6/20). Most common commensals were coagulase-negative staphylococci (26/36) (Table 2). All KTR received preoperative antibiotics at the time of transplantation, primarily cefazolin (15/20), and vast majority received TMP/SMX prophylaxis, for Pneumocystis jirovecii, post-transplant (19/20). PAT was administered in 70% (14/20) cases of bacteremia for a median of 8.5 days (IQR 7-14), while six cases were left untreated (Table 2). In contrast, majority of cases with common commensals were not treated (75%, 27/36). Of the cases treated (9/36), median duration of therapy was 7 days (IQR 5-14). No cases of infection with the same organism identified in the donor blood culture were reported in KTR within 30 days of transplantation. Conclusion KTR donors with bacteremia who were treated received a median of 8.5 days of PAT with no instances of breakthrough infection. In contrast, majority of donor blood cultures with organisms classified as common commensals were not treated and did well. Future studies are needed to assess whether perioperative antibiotics coupled with TMP/SMX prophylaxis post-transplantation are sufficient in select cases of transplantation from donors with bacteremia. Disclosures All Authors: No reported disclosures

scholarly journals Expression of Senescence Marker TIGIT Identifies Polyfunctional Donor-Reactive CD4+ T Cells Preferentially Lost After Kidney Transplantation

2021 ◽  
Vol 12 ◽  
Author(s):  
Amy C. J. van der List ◽  
Nicolle H. R. Litjens ◽  
Mariska Klepper ◽  
Michiel G. H. Betjes
Keyword(s):  
T Cells ◽  
Kidney Transplantation ◽  
T Cell ◽  
Expression Profile ◽  
Cd4 T Cells ◽  
Effector Memory ◽  
Cell Phenotype ◽  
Kidney Transplant Recipients ◽  
Post Transplantation ◽  
Cytokine Expression Profile

Development of T-cell hyporesponsiveness to donor antigen may explain the substantial decreased risk for acute rejection in the years following kidney transplantation. The underlying mechanisms of donor-specific hyporesponsiveness (DSH) are largely unknown but may allow for lowering of immunosuppressive medication. Due to the onset of DSH being more rapid and pronounced in older recipients (+55 years), we hypothesized that immunosenescence/exhaustion of T lymphocytes would be a contributing factor. This study tested whether donor-reactive recipient T cells become hyporesponsive due to exhaustion from continuous stimulation by donor antigen. Circulating donor-reactive T cells of both young and elderly stable kidney transplant recipients (N=17) before and 3-5 years after transplantation were analyzed at the single cell level for expression of exhaustion markers by multi-parameter flow cytometry followed by unsupervised and unbiased clustering. Clusters containing cells of a particular expression profile with significant differential abundance after transplantation were identified and further analyzed. Unexpectedly, our results do not demonstrate an increase in exhausted donor antigen-reactive T cells post transplantation. Instead, we demonstrate a significant decrease in donor antigen-reactive CD4+ T cells expressing T cell immunoglobulin and ITIM domain (TIGIT) long after transplantation. Further analysis at earlier timepoints indicated that this decrease is already present at six months post transplantation. Characterization of these CD4+ T donor-reactive cells expressing TIGIT revealed them to have a predominantly central and effector memory T cell phenotype and a highly poly-functional cytokine expression profile. This study has therefore identified TIGIT as a marker for a previously undescribed polyfunctional donor-reactive CD4+ T cell population whose decline following kidney transplantation may explain development of DSH.

Association Between CYP3A4 and CYP3A5 Genotypes and Cyclosporine's Blood Levels and Doses among Jordanian Kidney Transplanted Patients

2019 ◽  
Vol 20 (8) ◽  
pp. 682-694 ◽  
Author(s):  
Sahar El-Shair ◽  
Mohammad Al Shhab ◽  
Khaled Zayed ◽  
Moaath Alsmady ◽  
Malek Zihlif
Keyword(s):  
Kidney Transplantation ◽  
Strong Association ◽  
Mean Difference ◽  
Allele Frequencies ◽  
Assay Method ◽  
Therapeutic Window ◽  
Blood Levels ◽  
Nucleotide Polymorphisms ◽  
Significant Difference ◽  
The Mean

Background: Cyclosporine is used as an immunosuppressive agent in kidney transplantation. It has a narrow therapeutic window. Cyclosporine is predominantly metabolized by CYP3A4 and CYP3A5. The most common Single Nucleotide Polymorphisms (SNPs) affecting cyclosporine metabolism (CYP3A4*1B, CYP3A4*1G, CYP3A4*22 and CYP3A5*3) were investigated among Jordanian kidney transplanted patients to find out the genotypes and allele frequencies of these SNPs. Additionally, this study investigated whether genotypes of CYP3A4 and CYP3A5 affect C2 blood levels, dosing of cyclosporine and the prevalence of acute rejection. Methods: Blood samples of 109 adult patients taking cyclosporine as their primary immunosuppressant for kidney transplantation were collected from the Prince Hamzah Hospital, Amman, Jordan. Patients’ first C2 blood levels and their first two given doses were collected. Patients were genotyped for the four SNPs using Polymerase Chain Reaction- restriction Fragment Length Polymorphism (PCR-RFLP) assay method. Results: Allele frequencies among Jordanian patients for CYP3A4*1B, CYP3A4*1G, CYP3A4*22 and CYP3A5*3 were 0.037, 0.399, 0.037 and 0.271, respectively. There was a significant association between CYP3A4*22 and mean difference in the second and first given doses (P=0.034). There was a big difference between CYP3A4*22 and the mean of the first C2 blood levels (P=0.063). Conclusion: There was a strong association between CYP3A4*22 and the mean difference between the second and first given doses. There was a trend of significant difference between the mean of the first C2 blood levels among heterozygous CYP3A4*22 patients. Pharmacogenomics may hold promise in assisting the prediction of the best cyclosporine dose and C2 blood level among Jordanian kidney transplant patients.

The Economic Burden of Post-transplant Events in Renal Transplant Recipients

2021 ◽  
Vol 3 (4) ◽  
Author(s):  
Gihan Hamdy Elsisi
Keyword(s):  
Kidney Transplantation ◽  
Acute Rejection ◽  
Real Life ◽  
Calcineurin Inhibitors ◽  
Therapeutic Index ◽  
Medical Community ◽  
Blood Levels ◽  
Renal Transplant Recipients ◽  
Post Transplantation ◽  
Stage Renal Disease

Kidney transplantation (KT) is considered the optimum treatment choice for end stage renal disease (ESRD) both from a clinical and economic perspective. The incidence of acute rejection (AR) from KD could differ according to different patient and donor characteristic, as well as, the type of immunosuppressant agent allocated. Thus, it is crucial to carefully examine the costs associated with the type of immunosuppressant agents as they directly affect the clinical outcomes of recipients. Tacrolimus which is one of the Calcineurin inhibitors (CI) have proven a huge success in kidney transplantation and are considered the cornerstone therapy post transplantation. Since the expiry of its patent in 2008, generic versions have been introduced in the market. While it has been widely accepted in the medical community to switch from brand to generic drug products provided that they have proven therapeutic bioequivalence, the switch has been documents to be sensitive case with particular products which are characterized by a narrow therapeutic index (NTI). Their concern is that most of the bioequivalence studies are conducted in health volunteers’ whom do not suffer any comorbidity which is not the case in real life settings. González et al., 2017 note that this conversion affected its dose and blood levels which lead to the occurrence of acute rejection episodes due to under immunosuppression and report that infectious adverse events occurred as a result of over immunosuppression. Another important observation that there was a post serum creatinine increase after the formulation conversion and also patients experienced greater incidence of magnesium wasting, and more episodes of rejection which led to greater institutional costs of care. These findings highlight that cost containment policies need to be revisited especially with NTI drugs as their extra monitoring costs might actually off-set the savings of the generic product in the short term.

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