Anna Sadowska

Introduction Early prognostic markers that identify high-risk patients could lead to increased surveillance, personalized immunosuppression, and improved long-term outcomes. The aim of this prospective study was to assess whether urine levels of CCL2 and CXCL10 can be valuable, non-invasive source of information about ongoing immune inflammation, tubular injury, progression of fibrosis and other damage features in the kidney allograft. Materials and Methods In this prospective study 40 patients who underwent a protocolar biopsy within 1 year post kidney transplant were included. The levels of chemokines CCL2 and CXCL10 with reference to creatinine in urine were assayed in all patients. Based on biopsy results research group (N=25) with diagnosis of BKV nephropathy, IFTA II-III, peritubular capillaritisis, C4d or rejection was selected. Patients with normal biopsy results were included as control group (N=15). CCL2 and CXCL10 levels were evaluated in individual groups. Chi-square test or Fisher exact test were used for categorical variables and 2-sample t-test for continuous variables. Correlations were determined using Spearman and Pearson rank correlation coefficients. P values less than 0.05 were considered significant. Results Median urinary CCL2-to-creatinine (Cr) ratio [ng/mmol] was significantly elevated in research group compared to control group (21.76 ± 18.57 vs 8.99 ±5.12, p=0.003). There was no statistical difference between groups regarding CXCL10/Cr ratio (7.96 ± 9.08 vs 5.58 ±5.7 p=0.32). Patients with BKV nephropathy (N=3) had much higher level of CCL2 [ng/l] than control group but the difference did not reach statistical significance (429.69 ± 166.49 vs 78.04 ±53.61, p=0.06). Discussion Urinary CCL2/Cr corresponds with ongoing damaging processes. The significance of CCL2 in BKV nephropathy should be further evaluated. Conclusion Urinary CCL2/Cr may be used as a non-ivasive tool useful for monitoring graft condition and predicting recipients with high risk of transplant kidney loss.

Introduction The exposure to mycophenolic acid (MPA) and drug effects might be due to inosine 5'-monophosphate dehydrogenase (IMPDH1) polymorphisms. Formation of lipid bodies in adipocytes associates with IMPDH translocation into those structures. In the mouse model of diet-induced obesity, MMF induced loss of body weight and fat content. Our study aims to evaluate whether IMPDH1 polymorphism rs2278294 correlates with malnutrition in kidney recipients treated with mycophenolate mofetil (MMF). Patients and Methods – 240 kidney recipients engrafted 1996-2009, longitudinal observation lasting at least five post-implantation years, treated with mycophenolate mofetil and either tacrolimus (n=100; 42%) or cyclosporine A (n=139; 58%). – BMI was calculated at 3,6,12, 24 and 60th post-transplant months. – Minimal BMI within three post-transplant months was regarded as baseline value. – SNP genetic variants of IMPDH1 (rs2278294) were genotyped by PCR-RFLP method. – Mixed models for repeated measurements after adjustment for baseline factors were used to test relation between rs2278294 polymorphism of IMPDH1 and BMI in 5 years follow-up (MIXED Procedure of SAS System). Results Genotypes frequencies for rs2278294 polymorphism of IMPDH1 were as follow: 27(11%) of AA homozygotes, 91(38%) GA heterozygotes and 122(51%) GG homozygotes In the subset of recipients with initially normal or diminished BMI(≤25kg/m2) there was a substantial increase of BMI at 6,12, 24 and 60 th post-tx months. Moreover, BMI increase was correlated with rs2278294 polymorphism of IMPDH1. Among allele G carriers (GG or GA) BMI gain was significantly slower than in AA homozygotes (p<0.0025; interaction effect). Mean values of BMI(kg/m2) at 3,6,12, 24 and 60 th months were as follow: 22.0 vs 22.5; 22.6 vs 23.6; 23.1vs 24.5; 23.6 vs 24.9 and 24,1 vs 24.8 kg/m2 in (GG or GA) and AA carriers, respectively. In cosequence, among G allele carriers 5% experienced seriously diminished BMI fulfilling malnutrition criteria (18.2, 18.2, 18.8 and 18.8, 19 kg/m2 at 3,6,12 24 and 60 th post-transplant months). In G allele carriers mycophenolate mofetil dimunition or withdrawal resulted solely in preserving the subset of patients prone to malnutrition. Conclusions Since the effect of rs2278294 on BMI was found at transplantation and persisted until 5th post-implantation year, we hypothesize that the variant of interest influences fat-tissue formation in humans.

Despite universal prophylaxis, late cytomegalovirus (CMV) infection occurs in a high proportion of kidney transplant recipients. We evaluated whether a specific viral T-cell response allows for the better identification of recipients who are at high risk of CMV infection after prophylaxis withdrawal. We conducted a prospective study in 19 pretransplant anti-CMV seronegative kidney graft recipients R- (18 from seropositive donors [D+] and one from a seronegative donor [D-]) and 67 seropositive recipients R(+) (59 from seropositive donors and eight from seronegative donors) who received antiviral prophylaxis with valganciclovir. The QuantiFERON-CMV (QF-CMV) assay was performed within the first and third months after transplantation. Blood samples were monitored for CMV DNAemia using a commercial quantitative nucleic acid amplification test (QNAT) that was calibrated to the World Health Organization International Standard. Twenty-one of the 86 patients (24%) developed CMV viremia after prophylaxis withdrawal within 12 months posttransplantation. In the CMV R(+) group, the QF-CMV assay yielded reactive results (QF-CMV[+]) in 51 of 67 patients (76%) compared with 7 of 19 patients (37%) in the CMV R(−) group (p = 0.001). In the CMV R(+) group, infection occurred in seven of 16 recipients (44%) who were QF-CMV(−) and eight of 51 recipients (16%) who were QF-CMV(+). In the CMV R(−) group, infection evolved in five of 12 recipients (42%) who were QF-CMV(−) and one of 7 recipients (14%) who were QF-CMV(+). No difference was found in the incidence of CMV infection stratified according to the QF-CMV results with regard to the recipients’ pretransplant CMV IgG serology (p = 0.985). Cytomegalovirus infection occurred in 15 of 36 patients (42%) with hypogammaglobulinemia (HGG) 90 days posttransplantation compared with two of 34 patients (6%) without HGG (p = 0.0004). Cytomegalovirus infection occurred in seven of 13 patients (54%) with lymphocytopenia compared with 14 of 70 patients (20%) without lymphocytopenia (p = 0.015). The multivariate analysis revealed that the nonreactive QuantiFERON-CMV assay was an independent risk factor for postprophylaxis CMV infection. In kidney transplant recipients who received posttransplantation prophylaxis, negative QF-CMV results better defined the risk of CMV infection than initial CMV IgG status after prophylaxis withdrawal. Hypogammaglobulinemia and lymphocytopenia were risk factors for CMV infection.

Aim of the study was to assess the impact of the recipient and donor interferon lambda-3 (IFNL3) single-nucleotide polymorphisms (SNPs) rs12979860 and rs8099917 on the course of hepatitis C virus (HCV) reinfection following liver transplantation. Material and methods : The study involved...

BACKGROUND Rapid bone loss occurs early after liver transplantation (Tx), concomitantly with intensified bone turnover. In the present study we investigated the effect of bisphosphonates (bisph) added to vitamin D (vitD) and calcium on bone mineral density (BMD) and bone biomarkers in liver graft recipients in the first posttransplant year. MATERIAL AND METHODS In 28 patients BMD was determined at the third month after Tx. In case of osteopenia (Tscore ≤-1.0) and no contraindications, oral bisph was started for 1 year (group BP, n=14); other patients served as controls (CON, n=14). The changes in BMD and biomarkers of bone formation were osteocalcin (OC), bone alkaline phosphatase (BAP), and resorption. Study endpoints were active isoform 5b of the tartrate-resistant acid phosphatase (TRACP5b), serum pyridinoline crosslinks (PYD), and urine excretion of deoxypyridinoline (Dpd) crosslinks. RESULTS In 19 (68%) patients, reduced BMD (T-score ≤1.0) was observed at baseline. The changes in lumbar BMD in BP and CON groups were 5.2% and 1.5%, respectively, not reaching statistical significance. Baseline PYD, Dpd/creat, and OC were elevated in all patients, indicating high bone turnover. We observed decrease in PYD and Dpd/creat in both groups; however, OC decreased only under bisph therapy. Increase in BAP was observed in the control group but not in the BP group. The changes in BAP and OC were significantly different (p<0.01). CONCLUSIONS Combining bisph with vitD and calcium is an effective bone- sparing strategy in liver transplant recipients in the first posttransplant year. Bisph more efficiently decreased the rate of bone turnover than vitD and calcium alone.