Is There a Long-Term Risk for Donors With Heterozygous MEFV Mutation After Kidney Donation?

BACKGROUND: Familial Mediterranean fever (FMF) is an autosomal-recessive autoinflammatory disorder manifested severely by systemic amyloidosis. It has been hypothesized that heterozygous carriers may also have susceptibility to certain symptoms or even diseases. Because the living kidney donors of patients with FMF are generally relatives of the kidney recipients, there is a high possibility that the donors will have a heterozygous mutation of the FMF gene. The goal of this study was to investigate the long-term kidney function of donors who are carriers of the Mediterranean fever (MEFV) gene. METHODS: The medium- to long-term outcomes of 12 asymptomatic donors were compared with MEFV gene carriers and 24 non-FMF recipients' donors. RESULTS: Heterozygous carriers and the control group were similar with respect to age, sex, and follow-up period. The preoperative estimated glomerular filtration rate and 24-hour urine proteinuria levels were similar in the MEFV carrier and control groups. Four years after the donation, both groups had similar estimated glomerular filtration rates, but the change in 24-hour urine protein was statistically higher in the MEFV carrier group, and no significant change was observed in the control group (P = .004). At the end of the follow-up period, neither overt proteinuria nor kidney failure was seen in either group. CONCLUSIONS: This study showed that the medium- to long-term results of the kidney donors who are carriers of the MEFV gene seem to be safe. However, there was more of a tendency for an increase in proteinuria in the MEFV gene carriers compared with control subjects, which necessitated further long-term care for these donors.

Average Tacrolimus Trough Level in the First Month After Transplantation May Predict Acute Rejection.

BACKGROUND: Although tacrolimus is one of the essential drugs used for the prevention of rejection in kidney recipients, target trough levels are not well established. In this study, we aimed to investigate the association between average tacrolimus trough levels (TTLs) of the first month after transplantation and biopsy-proven acute rejection (BPAR) during the first 12 months after transplant. METHODS: A total of 274 patients who underwent kidney-alone transplantation between 2002 and 2014 were enrolled in the study. Average TTLs of the first month were assessed by means of receiver operating characteristic (ROC) curve analysis to discriminate patients with and those without BPAR. Univariate and multivariate Cox proportional hazards models were used to determine the effect of average TTLs of the first month on BPAR. RESULTS: According to ROC curve analysis, the highest area under the curve (AUC) was obtained from 8 ng/mL (AUC = 0.73 ± 0.11; 95% confidence interval [CI], 0.62-0.84). Forty-two (31.8%) of the 132 patients with average TTLs <8 ng/mL and 13 (9.1%) of 142 patients with ≥8 ng/mL had BPAR during the first 12 months after transplant (P < .001). In univariable analysis, average TTLs of the first month <8 ng/mL were associated with higher risk of BPAR (P < .001), and the significance remained in Cox multivariable analysis (hazard ratio, 2.79; 95% CI, 1.76-3.82; P = .001). No significant differences were observed in the glomerular filtration rate, cytomegalovirus, BK viremia, or BK nephropathy between groups at post-transplant month 12. CONCLUSIONS: Keeping the average TTLs of the first month after transplantation at ≥8 ng/mL not only prevents BPAR occurrence but also minimizes the toxic effects of the use of a single-trough level.

Risk Factors of Hyperuricemia After Renal Transplantation and Its Long-term Effects on Graft Functions.

BACKGROUND: Hyperuricemia is a common complication in renal transplant recipients. Recent studies have suggested that hyperuricemia may contribute to the deterioration of graft function. METHODS: In this study, we aimed to investigate the risk factors related to hyperuricemia and the effects of hyperuricemia on graft dysfunction, graft survival, cardiovascular events, and mortality rates. Between the years 2005 and 2016, 141 renal transplantation patients with at least 5 years of follow-up were included in this retrospective cohort study. Multi-linear regression analysis was used to determine the relationship between mean serum uric acid level and estimated glomerular filtration rate (eGFR). RESULTS: The average transplant age was 37.1 ± 12.1 years and the average follow-up time was 83.09 ± 20.30 months; the prevalence of patients with hyperuricemia was 39 (27.6%). The mean uric acid levels were higher in women (P < .001) in the condition of dyslipidemia (P = .026), ß-blocker usage (P = .002), and thiazide diuretics (P = .020). Patients with hyperuricemia (P < .001), new-onset hypertension (P = .027), ß-blocker usage (P = .005), and thiazide diuretics (P = .040) had statistically different eGFR levels than other recipients. Multivariant regression analyses showed that eGFR levels after transplantation were correlated with mean uric acid levels (ß = -0.46, P = .001), donor age (ß = -0.18, P = .048), recipient age (ß = -0.28, P = .0003), and mean hemoglobin levels (ß = 0.31, P = .003). CONCLUSIONS: There was no difference in graft loss, general mortality, and cardiovascular events between normo-uricemic and hyperuricemic groups. Increased uric acid levels contribute to eGFR decline in patients with renal transplantation. On the other hand, effects of uric acid levels on graft survival, cardiovascular events, and general mortality are still controversial.

Prevalence and Risk Factors of BK Viremia in Patients With Kidney Transplantation: A Single-Center Experience From Turkey.

BACKGROUND: BK virus is the cause of nephropathy, which can progress to graft loss after kidney transplantation. In this study, we aimed to investigate the prevalence and risk factors of BK viremia in patients with kidney transplantation at our center. METHODS: This was a retrospective single-center study. We included recipients transplanted between 2010 and 2015. Patients were stratified according to BK virus DNA follow-up values into three groups (0-999 copies/mL, 1000-9999 copies/mL and ≥10,000 copies/mL). The parametric t test and the non-parametric χ2 test were used to detect differences between groups. Multivariate analysis was used to identify risk factors for BK viremia. RESULTS: One hundred eighty-three patients were included in the study, with mean follow-up time of 33.6 ± 14.9 months. BK viremia prevalence was found 15.8% (n = 29), and time to detection of viremia was 7.6 months. Cadaveric transplantation and matching human leukocyte antigen (HLA) A24 and HLA B55 subgroups were found to be independent risk factors for BK viremia [odds ratio (OR), 3.65; 95% confidence interval (CI), 1.42-9.39; P < .001; OR, 4.94; 95% CI, 1.84-13.2; P < .001 and OR, 14.03; 95% CI, 1.07-183.5; P = .04, respectively]. Risk factors for BKV level ≥10,000 copies/mL cadaveric transplantation, male sex, and HLA A24 matching (OR, 4.53; 95% CI, 1.49-13.7; P < .001; OR, 3.47; 95% CI, 1.11-10.86; P = .03 and OR, 3.63; 95% CI, 1.08-12.1; P = .03, respectively). CONCLUSIONS: Patients should be followed more carefully for BK viremia who have cadaveric transplantation, are male, and have matching in certain HLA groups, which were independent risk factors in the present study. Our results are important to individualize screening methods and provide early diagnosis in our country.

Urgency Priority in Kidney Transplantation: Experience in Turkey.

BACKGROUND: In Turkey, according to the directions of National Organ and Tissue Transplant Coordination System, a system has been established since 2008 of urgency priority for kidney transplantation in cases with imminent lack of access for either hemodialysis or peritoneal dialysis. In this study, we compared patient and graft outcomes between patients on the national waiting list having urgency priority for kidney transplantation (UKT) and those having the other kidney from the same deceased donor (control group). METHODS: We examined retrospective data of patients, who underwent transplantation under urgency priority allocation in Turkey from 2010 to 2014 and compared that group with other patients receiving kidney transplants from the same deceased donors (control group). Then we compared these patients for early and long-term patient and graft outcomes. RESULTS: Forty-seven patients had UKT, and 40 patients received transplants from the same deceased donors. Mean follow-up of patients after transplantation was 18 ± 12 months. Eight patients with UKT and 4 patients in the control group lost their grafts. At follow-up, 7 patients died in the UKT group, and 4 patients died in the control group. Patient survival in the UKT group was 90% at 1 year and 83% at 2 years, and in the control group was 93% at 1 year and 84% at 2 years (P = .384). Graft survival was 87% at 1 year and 81% at 2 years in UKT, and 91% at both 1 and 2 years in the control group (P = .260). CONCLUSIONS: Although patients with UKT showed lower graft and patient survivals than the control group, the difference was statistically nonsignificant. UKT can be an obligatory treatment model for patients with lack of vascular or peritoneal access for dialysis.

Pregnancy After Kidney Transplantation: Outcomes, Tacrolimus Doses, and Trough Levels.

Although pregnancy after kidney transplantation has been considered as high risk for maternal and fetal complications, it can be successful in properly selected patients. It is well known that pregnancy can induce changes in the plasma concentrations of some drugs; however, there has been very limited information about tacrolimus pharmacokinetics during pregnancy. In this study, we evaluated the tacrolimus doses, blood levels, and the outcomes of pregnancies in kidney allograft recipients. From 2004 to 2014, we found 16 pregnancies in 12 kidney allograft recipients at our center. We reviewed the files and data reports including fetal outcomes, graft function, complications, tacrolimus trough levels, and doses. We analyzed the tacrolimus trough levels and doses before pregnancy, during pregnancy (monthly), and in the postpartum period. Throughout the pregnancy, we aimed to achieve tacrolimus trough levels between 4 and 7 ng/mL. All patients were on triple immunosuppression, including tacrolimus, azathioprine, and prednisolone. In total, 11 of 16 (68.7%) pregnancies were successful, with a mean weight gain of 12.5 ± 1.66 kg. One patient developed gestational diabetes mellitus and 2 had preeclampsia. Although 5 of 11 babies were found to have low birth weight, 4 of these were premature. Two patients lost their grafts, 1 due to acute rejection and the second due to progression of chronic allograft dysfunction. We have shown that tacrolimus doses need to be significantly increased to keep appropriate trough levels during pregnancy (the doses: before, 3.20 ± 0.9 mg/day; first trimester, 5.03 ± 1.5; second trimester, 6.50 ± 1.8; third trimester, 7.30 ± 2.3; post-partum, 3.5 ± 0.9). In conclusion, the dose of tacrolimus needs to be increased to provide safe and stable tacrolimus trough levels during pregnancy. Although pregnancy can be successful in most cases, it should be kept in mind that there is an increased risk of maternal and fetal complications, including allograft loss, low birth weight, spontaneous abortus, and preeclampsia.

Compression of ultrashort laser pulses in planar hollow waveguides: a stability analysis.

We investigate compression of ultrashort laser pulses by nonlinear propagation in gas-filled planar hollow waveguides, using (3+1)- dimensional numerical simulations. In this geometry, the laser beam is guided with a fixed size in one transverse dimension, generating significant spectral broadening, while it propagates freely in the other, allowing for energy up-scalability. In this respect the concept outperforms compression techniques based on hollow core fibers or filamentation. Small-scale self-focusing is a crucial consideration, which introduces mode deterioration and finally break-up in multiple filaments. The simulation results, which match well with initial experiments, provide important guidelines for scaling the few-cycle pulse generation to higher energies. Pulse compression down to few-cycle duration with energies up to 100 mJ levels should be possible.

Terahertz radiation source in air based on bifilamentation of femtosecond laser pulses.

A new terahertz (THz) source in air based on the bifilamentation of femtosecond laser pulses is reported. This THz radiation is 1 order of magnitude more intense than the transition-Cherenkov THz emission from femtosecond laser filaments reported recently and shows different angular and polarization properties. We attribute it to the emission from a bimodal transmission line created by two plasma filaments.