Association between Kidney Donor Risk Index, kidney graft function and histological changes in early post-transplant graft biopsy.

Background: Proper assessment of donor organ quality is crucial for optimal kidney allocation and best long-term outcomes. The aim of this study was to analyze the association between the Kidney Donor Risk Index (KDRI) and histological parameters in early post-transplant graft biopsy in a Polish cohort of kidney transplant recipients. Methods: In 418 consecutive kidney transplant recipients, a histological evaluation of very early [at median 11 (9-13) post-transplant day] protocol core needle biopsy was performed and analyzed according to the Banff classification. Subjects were divided into quartiles of the KDRI value. Kidney graft function, patient and graft survival were also analyzed over a median follow-up period of 44 (26-56) months. Results: There was a significant trend toward greater intensity of chronic histology changes along the KDRI quartiles (χ2 = 20.8; P < .001), including interstitial fibrosis, tubular atrophy, mesangial matrix increase and arteriolar hyalinosis. Stepwise multivariate regression analysis revealed that only higher KDRI value independently increased the severity of chronic graft injury (rpartial = 0.340, P < .001). KDRI values were valuable in the determination of both early and long-term graft function. Conclusion: The KDRI values correlate with chronic histological changes found in early post-implantation kidney biopsies and can also be helpful in the prediction of graft outcome.

Intestinal Permeability in Patients Early after Kidney Transplantation Treated with Two Different Formulations of Once-Daily Tacrolimus.

Adequate tacrolimus blood exposure is crucial in the early post-renal transplant period and a gut epithelial barrier integrity may play a role. We prospectively investigated several markers of intestinal permeability in recent kidney transplant recipients (KTRs) treated with different tacrolimus extended-release formulations. Within each of the 49 KTR pairs that received grafts from the same donor, an early randomized conversion was performed from twice-daily (Prograf) to once-daily tacrolimus formulation: Advagraf or Envarsus. Plasma zonulin, calprotectin, circulating lipopolysaccharide (LPS), LPS-binding protein (LBP), intestinal fatty acid binding protein (FABP-2), and CD-14 levels were measured. There was no difference in the recipient age, dialysis vintage, BMI, and residual diuresis between Advagraf and Envarsus groups. FABP-2 and LPS levels were significantly associated with tacrolimus trough level, 3-h level, and area under the curve (AUC) in the Envarsus but not in the Advagraf group. AUC was independently increased by LPS and decreased by age, FABP-2 concentration, and the use of Envarsus formulation as compared with Advagraf. Functional changes of gastrointestinal tract in patients treated with Envarsus may influence intestinal tacrolimus absorption to a greater extent than in Advagraf-treated KTRs and may lead to inadequate variability of tacrolimus exposure early after kidney transplantation.

Potential Utility of Neutrophil-to-Lymphocyte, Platelet-to-Lymphocyte, and Neutrophil, Lymphocyte, and Platelet Ratios in Differential Diagnosis of Kidney Transplant Acute Rejection: A Retrospective, Propensity Score Matched Analysis.

BACKGROUND Acute kidney transplant rejection can negatively affect long-term graft function. The neutrophil-to-lymphocyte ratio and platelet-to-lymphocyte ratio have been proposed as non-invasive predictors of acute rejection in stable kidney transplant recipients. The aim of this study was to validate the predictive value of these ratios, as well as neutrophil, lymphocyte, and platelet ratios in the diagnosis of acute rejection during the early post-transplant period. MATERIAL AND METHODS After propensity score matching, we compared 71 kidney recipients with biopsy-proven acute rejection with 71 patients without rejection and also subjects with different histologic types of rejection. All 3 types of blood cell count-derived ratios were calculated 6 and 3 days prior to biopsy and on the day of biopsy. RESULTS There were 15 patients with T cell-mediated rejection, 33 with vascular rejection, and 23 with antibody-mediated rejection. The values of all examined ratios did not differ between subgroups with and without rejection. However, at all post-transplant study time-points, patients with antibody-mediated rejection had significantly higher values of all analyzed ratios than subjects with other types of rejection. In multivariate regression models, higher values of blood cell count-derived ratios were independently associated with the occurrence of antibody-mediated rejection. CONCLUSIONS In the early post-transplant period, the values of neutrophil-to-lymphocyte, platelet-to-lymphocyte, and neutrophil, lymphocyte, and platelet ratios were similar in patients with and without an acute rejection episode, but significantly higher values were found in subjects with antibody-mediated rejection as compared with other types of rejection and those without rejection. High values of analyzed ratios in patients with satisfactory early kidney graft function may be helpful in selecting subjects with increased risk of subclinical antibody-mediated rejection.

Clinical Outcomes of Transplanted Kidneys from Deceased Donors Using Different Generic Preservation Solutions.

Background and Objectives: StoreProtect Plus® is a preserving solution for cold organ storage, with a composition identical to Institute Georges Lopez (IGL-1) solution. The aim of this single center study was to compare the clinical performance of StoreProtect Plus with the generic counterpart of University of Wisconsin preservation fluid, named SPS-1®. Materials and Methods: The clinical outcomes of 168 consecutive organs preserved with StoreProtect Plus solution and 167 organs preserved with SPS-1 solution were compared. During an 18-month post-transplant follow-up period, kidney graft function, the frequency of acute rejection, post-transplant diabetes, and infectious complications, as well as patient and graft survival were analyzed. Results: There was significantly more immediate graft function (IGF) (39.3 vs. 24.0%; p < 0.01) and less slow graft function (SGF) (38.7 vs. 51.5%; p < 0.05) in the StoreProtect Plus group in comparison with the SPS-1 group, whereas the occurrence of DGF was similar in both groups. Long-term kidney graft function was comparable. Multivariate regression analysis showed that the use of StoreProtect Plus vs. SPS-1 solution (rpartial = 0.217; p < 0.001) and the amount of residual diuresis (rpartial = 0.147; p < 0.001) independently increased the occurrence of IGF, whereas Scr > 1.5 mg/dL prior to organ procurement (rpartial = −0.198; p < 0.001), longer CIT (rpartial = −0.170; p < 0.01), and CVD donor death (rpartial = −0.214; p < 0.001) were associated with SGF. Conclusions: The higher occurrence of IGF was found in kidney transplant recipients whose organs were preserved using StoreProtect Plus solution as compared with SPS-1 solution. The two groups did not differ in kidney graft function, the frequency of post-transplant complications, as well as patient and graft survival.

Visual evoked potentials as a method for the prospective assessment of tacrolimus neurotoxicity in patients after kidney transplantation.

INTRODUCTION: Neurotoxicity, including optic nerve injury, is one of the most common adverse effects of tacrolimus, the principal calcineurin inhibitor used after kidney transplantation (KTx). The electrophysiologic measurements of both pattern visual evoked potentials (PVEP) and flash visual evoked potentials (FVEP) are valuable when drug-induced optic neuropathy is suspected. OBJECTIVES: To determine whether VEP measurement is a sensitive and repeatable method for monitoring tacrolimus neurotoxicity. MATERIAL AND METHODS: This prospective study focused on 35 patients (20 M, 15F, 69 eyes, mean age 43 ± 11 years) who were at a median of 3.0 (IQR, 2.2-3.7) months after KTx at the time of the initial VEP evaluation and were treated with tacrolimus since KTx. The follow-up VEP examination was done after a median of 24 (22-27) months (both VEP measurements followed the ISCEV standards). The P100 wave latency and amplitude for the 1° and 15' PVEP simulations, and the P2 wave latency and amplitude for the FVEP were analyzed. RESULTS: For the 1° checks, the P100 wave latency and amplitude values were significantly worse in the follow-up examination compared to the early post-transplant time-point. Independent associations between FVEP parameters and the tacrolimus blood trough level were observed in the follow-up examination but not at the early post-transplant period. The P2 wave latency correlated with the tacrolimus trough level only in patients treated with the twice-daily, but not the once-daily, tacrolimus formulation. The brain derived neurotrophic factor (BDNF) level correlated with the P100 (15') latency (R = 0.499; p = 0.005) and the P2 latency (R = 0.409; p = 0.025) only in patients treated with the once-daily, but not the twice-daily, tacrolimus formulation. CONCLUSION: The observations in this study may support the rationale for the use of VEP measurements as non-invasive monitoring of subclinical tacrolimus neurotoxicity.

Transplanted kidney loss during colorectal cancer chemotherapy: A case report.

BACKGROUND: The overall risk of de novo malignancies in kidney transplant recipients (KTRs) is higher than that in the general population. It is associated with long-lasting exposure to immunosuppressive agents and impaired oncological vigilance due to chronic kidney disease. Colorectal cancer (CRC), frequently diagnosed in an advanced stage, is one of the most common malignancies in this cohort and is associated with poor prognosis. Still, because of the scarcity of data concerning adjuvant chemotherapy in this group, there are no clear guidelines for the specific management of the CRCs in KTRs. We present a patient who lost her transplanted kidney shortly after initiation of adjuvant chemotherapy for colon cancer. CASE SUMMARY: A 36-year-old woman with a medical history of kidney transplantation (2005) because of end-stage kidney disease, secondary to chronic glomerular nephritis, and long-term immunosuppression was diagnosed with locally advanced pT4AN1BM0 (clinical stage III) colon adenocarcinoma G2. After right hemicolectomy, the patient was qualified to receive adjuvant chemotherapy that consisted of oxaliplatin, leucovorin and 5-fluorouracil (FOLFOX-4). The deterioration of kidney graft function after two cycles caused chemotherapy cessation and initiation of hemodialysis therapy after a few months. Shortly after that, the patient started palliative chemotherapy because of cancer recurrence with intraperitoneal spread. CONCLUSION: Initiation of adjuvant chemotherapy for colon cancer increases the risk of rapid kidney graft loss driven also by under-immunosuppression.

Increased EBV DNAemia after Anti-SARS-CoV-2 Vaccination in Solid Organ Transplants.

The reactivation of latent viruses during SARS-CoV-2 infection is well recognized, and coinfection with Epstein−Barr virus (EBV) has been associated with severe clinical cases of COVID-19 infection. In transplant patients, EBV infection presents a significant challenge. Assessing the potential impact of SARS-CoV-2 vaccinations on EBV infections in stable kidney and liver transplant recipients was the objective of our study. Ten solid-organ-transplant (SOT) patients (eight kidney and two liver) vaccinated with standard doses of mRNA COVID-19 vaccines were included. EBV DNA viral load measurements were conducted prior to the vaccination and during a follow-up period (at the first month and after six months) after the second vaccine dose. After the second dose, a significant increase in median viremia was observed (p < 0.01) in 9 patients, and in one patient, the reactivation of EBV infection was found. Six months later, the median viremia decreased significantly (p < 0.05). The EBV viral load should be closely monitored as it could lead to the earlier diagnosis and treatment of EBV-related complications. Despite experiencing a decrease in the viral load six months post-vaccination, some patients still had a viral load over the baseline, which increased the risk of potential complications.

Analysis of Complications and Recipients' and Graft Survival in Patients 60 Years of Age and Older in the Long-Term Follow-up Period After Kidney Transplant: A Single-Center, Paired Kidney Analysis.

BACKGROUND: Long-term results of kidney transplant (KTx) in older patients may differ from younger recipients owing to increased cardiovascular comorbidities. The study aimed to analyze surgical and nonsurgical complications that develop in the long-term follow-up period after KTx, and factors that influence results of KTx in recipients aged 60 years and older (≥60) compared with younger recipients (<60). METHODS: One hundred seventy-five patients aged ≥60 years and 175 patients aged <60 years who received a kidney graft from the same deceased donor were enrolled in the study. In the long-term follow-up period (3 months to 5 years after KTx) the incidence of surgical and nonsurgical complications, as well as patient and kidney graft survival, were compared. Additionally, the influence of early complications on patients and kidney graft survival was assessed. RESULTS: There were no differences between recipients aged ≥60 years compared with recipients aged <60 years in occurrence of surgical complications (graft artery stenosis: 0.6% vs 2.3%; ureter stenosis: 3.4% vs 1.1%; lymphocele: 6.9% vs 3.4%) and nonsurgical complications (urinary tract infection: 19.4% vs 23.4%; pneumonia: 8.6% vs 8.6%; cytomegalovirus infection: 6.3% vs 8%; new-onset diabetes after transplant: 16.6% vs 17.1%; cancer incidence: 5.7% vs 4.6%; acute rejection episode: 13.1% vs 17.1%). Five-year recipient survival was lower in a group of patients aged ≥60 years (death, 15.4% vs 8%; death with functioning graft, 12% vs 5.1%). CONCLUSIONS: The incidence of surgical and nonsurgical complications, as well as kidney-graft survival, in recipients aged ≥60 years in a 5-year follow-up period is comparable to younger recipients aged <60 years.

Kidney Graft Failure and Patient Survival Modelling Based on Competing Risks Under Nonproportional Hazards.

We analyze data on Silesian patients after kidney transplantation under competing events scenarios where time to death and time to graft failure are considered as absorbing competing events. Our objectives are to use model diagnostics in identifying violations of proportionality assumption under the framework of subdistribution and cause-specific hazards. We use the Fine-Gray proportional hazards model for the subdistribution. Under the cause-specific hazards (CSH) scenario we use the Cox proportional hazards model and Gray's time-varying coefficients model and available model diagnostics. We show that violation of proportional subdistribution hazards assumption may be conveniently identified using residual diagnostics and properly accounted for by involving time interactions with appropriate model predictors. We also show that although the nonproportional effects on cumulative incidence do not necessarily translate in those on cause-specific hazards, they often take place simultaneously, and a violation of the proportionality assumption needs to be checked rigorously. Time-varying effects have a profound impact on clinical inference under competing risks. They do not translate directly between the frameworks of subdistribution and cause-specific hazards because the cumulative incidence is obtained via integrating the cause-specific hazard weighted by the overall survival function. Also, a different definition of the risk set is in place under the cumulative incidence and CSH framework, respectively. However, a simultaneous violation of the proportionality assumption under both frameworks is still possible. Clinical inference may change considerably when such a violation occurs. Nonproportional effects may be properly identified under each framework using available model diagnostics.

Clinical insights into the role of immunosuppression in solid organ transplant recipients with COVID-19.

INTRODUCTION: The COVID-19 pandemic has disproportionately affected patients who have undergone solid organ transplantation (SOT). OBJECTIVES: We aimed to assess a cohort of transplant recipients who developed COVID­19, with a focus on immunosuppressive regimen, blood tacrolimus levels, clinical course, and patient and graft outcomes. PATIENTS AND METHODS: During the first 12 months of the pandemic, we identified ambulatory SOT recipients, including kidney, liver, and heart transplant recipients, diagnosed with SARS­CoV­2 infection. Baseline and follow­up data on graft function, immunosuppression, and patient and graft outcomes were assessed. RESULTS: Of the 2091 ambulatory patients, we identified 201 transplant recipients (9.6%) with SARS­CoV­2 infection (kidney transplant, n = 112; heart transplant, n = 56; liver transplant, n = 33). Patients after recent kidney (during 2015-2020) or heart (during 2020) transplant were significantly more often diagnosed with COVID ­19 than patients with a longer time since transplant. Additionally, blood trough tacrolimus levels measured during or shortly after COVID­19 in 23 kidney graft recipients were significantly increased by a median of 76.1% (interquartile range, 47.4%-109.4%) relative to predose trough levels. However, liver function parameters were not elevated, necessitating a tacrolimus dose reduction in 73.9% of the patients. CONCLUSIONS: In our study, kidney transplant recipients showed significant disturbances of tacrolimus metabolism, which may account for kidney function worsening during COVID­19. Moreover, infection was more common in patients with recent kidney or heart transplant, which suggests that the level of immunosuppression may affect morbidity related to SARS­CoV­2 infection.

The Relationship between Initial Tacrolimus Metabolism Rate and Recipients Body Composition in Kidney Transplantation.

There are several premises that the body composition of kidney transplant recipients may play a role in tacrolimus metabolism early after transplantation. The present study aimed at analyzing the relationship between the body composition parameters assessed by bioimpedance analysis (BIA) and initial tacrolimus metabolism. Immediately prior to transplantation, BIA using InBody 770 device was performed in 122 subjects. Tacrolimus concentration-to-dose (C/D) ratio was calculated based on the first blood trough level measurement. There was no difference in phase angle, visceral fat area, lean body mass index (LBMI) and the proportion of lean mass as a percentage of total body mass between the subgroups of slow and fast metabolizers. However, subjects with LBMI ≥ median value of 18.7 kg/m2, despite similar initial tacrolimus dose per kg of body weight, were characterized by a significantly lower tacrolimus C/D ratio (median 1.39 vs. 1.67, respectively; p < 0.05) in comparison with the subgroup of lower LBMI. Multivariate regression analysis confirmed that age (rpartial = 0.322; p < 0.001) and LBMI (rpartial = -0.254; p < 0.01) independently influenced the tacrolimus C/D ratio. A LBMI assessed by BIA may influence the tacrolimus metabolism in the early post-transplant period and can be a useful in the optimization of initial tacrolimus dosing.

Type 1 Diabetic Patients After Simultaneous Pancreas and Kidney Transplantation Have Less Intense Periodontal Inflammation Compared to Kidney Recipients Treated with Insulin.

BACKGROUND Long-term diabetes predisposes to pathological changes in periodontal tissues. Improvement in this respect can be expected in patients after pancreas transplantation. The aim of this study was to assess and compare the intensity of periodontium pathological lesions and inflammation markers concentration in gingival crevicular fluid (GCF) in patients with type 1 diabetes (T1D) after kidney (KTx) or simultaneous pancreas and kidney transplantation (SPK). MATERIAL AND METHODS The study included 20 T1D patients after SPK and 16 after KTx, and 15 non-diabetic kidney recipients (control). Periodontal clinical parameters and concentration of selected biochemical markers of inflammation in GCF were assessed. The following tests were used in statistical data analysis: Shapiro-Wilk test, the t test, the Mann-Whitney U tests, one-way ANOVA with Tukey's post hoc test, and χ² test (also with Yate's correction). Moreover, linear regression and Pearson or Spearman correlation coefficient was used. RESULTS There were no differences in modified Sulcus Bleeding Index (mSBI) and GCF volume between the SPK group and control group, whereas values of these parameters in the KTx group were higher than in the SPK and control groups. Maximal clinical attachment loss and pocket depth and Periotest values were higher in diabetic recipients compared to controls, and did not differ between SPK and KTx. The concentration of IL-1ß, MMP-8, resistin, TNFalpha, and YKL40 in the GCF in the KTx group was higher than in the SPK and control groups. In the combined group of T1D patients, there was a correlation between blood HbA1c and mSBI, GCF volume, and resistin, TNF-alpha and YKL40 concentrations, and between resistin concentration and mSBI. CONCLUSIONS T1D patients after SPK show lower levels of inflammatory markers in GCF and present reduced intensity of periodontitis compared to kidney recipients treated with insulin. The severity of morphological changes in periodontium in T1D patients after KTx or SPK is higher than in non-diabetic kidney recipients.

Advanced Leiomyosarcoma of the Retroperitoneal Space in a Kidney Transplant Recipient with a History of Peritoneal Dialysis: A Case Report.

BACKGROUND Leiomyosarcoma frequently occurs in patients who are on immunosuppressive therapy. It is the second most common sarcoma in this population and is often associated with Epstein-Barr virus (EBV) infection. We present a case of advanced leiomyosarcoma of the retroperitoneal space in a kidney transplant recipient and discuss additional risk factors for oncogenesis. CASE REPORT A 44-year-old woman with a history of peritoneal dialysis and kidney transplantation was diagnosed with multiple liver lesions. PET-CT scanning showed a metabolically active tumor in the left lumbar region with numerous liver focal lesions. The histological examination of the liver lesion biopsy identified advanced retroperitoneal leiomyosarcoma with a high proliferative index and liver involvement. Unexpectedly, the relation with EBV infection was not proven. The patient was treated with first-line doxorubicin, with the simultaneous reduction of immunosuppression. Owing to disease progression after 6 cycles, the patient received second-line chemotherapy based on gemcitabine and docetaxel, which was terminated owing to unacceptable toxicity, despite an observed response. Third-line trabectedin-based therapy with good tolerance and stabilization of disease after 20 months was being maintained at the time of this report. CONCLUSIONS The increased cancer mortality in solid-organ transplant recipients requires an individualized approach and increased post-transplantation screening according to additional specific cancer risk factors. A further consideration is the hypothetical relevance of long-term peritoneal membrane irritation in peritoneal dialysis patients.

Safety of Antithymocyte Globulin Use in Kidney Graft Recipients During the COVID-19 Pandemic.

BACKGROUND There are many safety concerns regarding the use of antithymocyte globulin (ATG) in kidney transplant recipients (KTRs) during the ongoing COVID-19 pandemic. Hereby, we present our recent experience with ATG administration both as induction therapy and as an anti-rejection treatment. MATERIAL AND METHODS We retrospectively analyzed all patients transplanted during the first 12 months of the COVID-19 pandemic who were treated with thymoglobulin. The ATG dosing, lymphocyte number and percentage in blood smear, adverse effects (thrombocytopenia and infectious complications), and kidney graft function up to 12 months and patients' outcomes were analyzed and compared to KTRs who received basiliximab induction. RESULTS During pandemic, a total of 31 patients were treated with ATG and 59 received basiliximab. The median cumulative ATG doses were 275 (175-325) mg in the induction subgroup and 263 (200-275) mg in the anti-rejection treatment subgroup. Mild thrombocytopenia was noted in 7 (22.6%) and 13 (29.5%) patients, respectively. There were more infectious complications among patients treated with ATG as compared with the basiliximab subgroup (32.3 vs 10.2%, P<0.01), but there were similar incidence rates of thrombocytopenia. Kidney graft function up to 12 months after transplant was comparable (1.1 [1.0-1.9] vs 1.1 [1.0-1.4] mg/dl, respectively). CONCLUSIONS 1. ATG use in the induction protocol or as the anti-rejection treatment during the COVID-19 pandemic appears to be safe and the risk of adverse events is acceptable. 2. During the COVID-19 pandemic the necessary use of ATG should not be postponed, especially in KTRs with increased immunologic risk.

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.

COVID-19 infection in solid organ transplant recipients: A single-center experience with patients immediately after transplantation.

In our transplant center, infection with SARS-CoV-2 virus was confirmed in 4 organ transplant recipients (3 kidney and 1 liver transplant recipients) during their early post-transplant hospital stay. In this paper, we report the basic characteristics, management, clinical course, and outcomes of these patients.

Is Metabolic Acidosis a Novel Risk Factor for a Long-Term Graft Survival in Patients after Kidney Transplantation?

BACKGROUND: Results of both experimental and clinical studies suggest that metabolic acidosis (MA) contributes to the progression of chronic kidney disease (CKD) and mortality in CKD patients. It is unknown whether the same relationship exists in kidney transplantation (KTx) patients. The aim of this observational study was to examine this relationship between MA and both mortality and renal outcomes in patients after KTx. METHODS: Four hundred eighty-six (290 male; 196 female) patients aged 48 ± 12 years, at least 1 year after KTx, were analyzed. Blood HCO3- was measured, and patients were then observed over 3 years. MA was defined as the blood HCO3- concentration <22 mmol/L. The end points of survival analysis were death and initiation of dialysis therapy. In patients who did not reach the above-mentioned end points, the difference between final (after 3 years of follow-up) and initial estimated glomerular filtration rate (eGFR) was calculated. RESULTS: MA was initially diagnosed in 57 (12%) patients after KTx. Three-year patient survival was 89.5% in the MA group and 97.4% in the non-MA group (p = 0.001). Three-year graft survival was 73.7% for patients with MA and 93.0% for patients without MA (p < 0.001). In patients with MA who did not reach study end points, blood bicarbonate concentration at baseline correlated positively with a change in eGFR (R = 0.48, p = 0.002, n = 36). Such a correlation was not found in patients without MA (n = 388). CONCLUSIONS: (1) MA significantly increases the risk of mortality in patients after KTx. (2) The intensity of MA may be associated with progression of transplanted kidney dysfunction in KTx patients.

The Effect of Maintenance Treatment with Twice-Daily or Prolonged Once-Daily Tacrolimus Formulation on Visual Evoked Potentials in Stable Kidney Transplant Recipients.

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.

Number of Regularly Prescribed Drugs and Intrapatient Tacrolimus Trough Levels Variability in Stable Kidney Transplant Recipients.

High intra-patient variability (IPV) of tacrolimus levels is associated with poor long-term outcome after transplantation. We aimed to evaluate whether the number of regularly prescribed medications is associated with the tacrolimus IPV. We have studied 152 kidney transplant recipients (KTRs) with mean post-transplant time of 6.0 ± 3.1 years. The coefficient of variation (CV) as a measure of IPV was calculated in each individual patient. Data concerning the type and number of currently prescribed medications were collected. The participants were divided into four groups, based on the number of regularly prescribed drugs (≤3, 4-6, 7-9, ≥10 drugs, respectively). There was an increasing trend for median CV, proportional to the increasing number of medications [group 1: 0.11 (interquartile range, 0.08-0.14), group 2: 0.14 (0.01-0.17), group 3: 0.17 (0.14-0.23), group 4: 0.17 (0.15-0.30); p value for trend = 0.001]. Stepwise backward multivariate regression analysis revealed that the number of medications [partial correlation coefficient (rpartial) = 0.503, p < 0.001] independently influenced the tacrolimus IPV. Concomitant steroid or diuretics use increased IPV only in Advagraf-treated KTRs, whereas proton-pump inhibitor or statin use increased IPV in the Prograf group but not in the Advagraf group. A large number of concomitant medications significantly increases the tacrolimus IPV in stable KTRs.

Influence of Chronic Periodontitis on the Long-Term Mortality and Cardiovascular Events in Kidney Transplant Recipients.

Chronic periodontitis (CP) is associated with cardiovascular disease and mortality in different populations. The aim of this study was to examine an association of CP with hard endpoints in patients after kidney transplantation during a 15-year follow-up period. Study group consist of 117 patients (77M/40F, median age 44 years) divided into two subgroups: those with initially advanced CP (CPITN 3-4) and those with no or moderate CP (CPITN 0-2). All cardiovascular events, graft losses, and re-transplantations were recorded. All deaths were noted and verified, including those occurred after the return to dialysis therapy, the causes of death were identified. Cox regression with Firth's penalized maximum likelihood models were used for data analysis. During the observation period, 49 deaths occurred. Advanced CP (n = 35) was not associated with overall mortality but was associated with increased risk of death with functioning graft (DWFG) [HR 3.54 (1.20-10.45); p < 0.05]. Risk of graft loss was not associated with CP status. In conclusion, an advanced CP was independently associated with increased risk of DWFG, but not all-cause or cardiovascular mortality after renal transplantation.