Safety and efficacy of one and two booster doses of SARS-CoV-2 mRNA vaccines in kidney transplant recipients: A randomized clinical trial.

BACKGROUND: Kidney transplant recipients are at risk for a severe course of COVID-19 with a high mortality rate. A considerable number of patients remains without a satisfactory serological response after the baseline and adjuvant SARS-CoV-2 vaccination schedule. METHODS: In this prospective, randomized study, we evaluated the efficacy and safety of one and two booster doses of mRNA vaccines (either mRNA-1273 or BNT162b2) in 125 COVID-19 naive, adult kidney transplant recipients who showed an insufficient humoral response (SARS-CoV-2 IgG <10 AU/ml) to the previous 2-dose vaccination schedule. The primary outcome was the difference in the rate of a positive antibody response (SARS-CoV-2 IgG ≥10 AU/ml) between one and two booster doses at 1 month after the final booster dose. RESULTS: A positive humoral response was observed in 36 (62%) patients receiving two booster doses and in 28 (44%) patients receiving one booster dose (odds ratio [OR], 2.10, 95% confidence interval [CI], 1.02-4.34, p = .043). Moreover, median SARS-CoV-2 IgG levels were higher with two booster doses (p = .009). The number of patients with positive virus neutralizing antibody (VNA) levels was numerically higher with two booster doses compared to one booster dose, but without statistical significance (66% vs. 50%, p = .084). There was no significant difference in positive seroconversions rate and antibody levels between mRNA-1273 and BNT162b2. CONCLUSION: A higher number of kidney transplant recipients achieved a positive antibody response after two booster doses compared to one booster dose.

A Randomized Trial of Valganciclovir Prophylaxis Versus Preemptive Therapy in Kidney Transplant Recipients.

SIGNIFICANCE STATEMENT: Although cytomegalovirus (CMV) infection is an important factor in the pathogenesis of kidney allograft rejection, previous studies have not determined the optimal CMV prevention strategy to avoid indirect effects of the virus. In this randomized trial involving 140 kidney transplant recipients, incidence of acute rejection at 12 months was not lower with valganciclovir prophylaxis (for at least 3 months) compared with preemptive therapy initiated after detection of CMV DNA in whole blood. However, prophylaxis was associated with a lower risk of subclinical rejection at 3 months. Although both regimens were effective in preventing CMV disease, the incidence of CMV DNAemia (including episodes with higher viral loads) was significantly higher with preemptive therapy. Further research with long-term follow-up is warranted to better compare the two approaches. BACKGROUND: The optimal regimen for preventing cytomegalovirus (CMV) infection in kidney transplant recipients, primarily in reducing indirect CMV effects, has not been defined. METHODS: This open-label, single-center, randomized clinical trial of valganciclovir prophylaxis versus preemptive therapy included kidney transplant recipients recruited between June 2013 and May 2018. After excluding CMV-seronegative recipients with transplants from seronegative donors, we randomized 140 participants 1:1 to receive valganciclovir prophylaxis (900 mg, daily for 3 or 6 months for CMV-seronegative recipients who received a kidney from a CMV-seropositive donor) or preemptive therapy (valganciclovir, 900 mg, twice daily) that was initiated after detection of CMV DNA in whole blood (≥1000 IU/ml) and stopped after two consecutive negative tests (preemptive therapy patients received weekly CMV PCR tests for 4 months). The primary outcome was the incidence of biopsy-confirmed acute rejection at 12 months. Key secondary outcomes included subclinical rejection, CMV disease and DNAemia, and neutropenia. RESULTS: The incidence of acute rejection was lower with valganciclovir prophylaxis than with preemptive therapy (13%, 9/70 versus 23%, 16/70), but the difference was not statistically significant. Subclinical rejection at 3 months was lower in the prophylaxis group (13% versus 29%, P = 0.027). Both regimens prevented CMV disease (in 4% of patients in both groups). Compared with prophylaxis, preemptive therapy resulted in significantly higher rates of CMV DNAemia (44% versus 75%, P < 0.001) and a higher proportion of patients experiencing episodes with higher viral load (≥2000 IU/ml), but significantly lower valganciclovir exposure and neutropenia. CONCLUSION: Among kidney transplant recipients, the use of valganciclovir prophylaxis did not result in a significantly lower incidence of acute rejection compared with the use of preemptive therapy. CLINICAL TRIAL REGISTRY NAME AND REGISTRATION NUMBER: Optimizing Valganciclovir Efficacy in Renal Transplantation (OVERT Study), ACTRN12613000554763 .

Insufficient response to mRNA SARS-CoV-2 vaccine and high incidence of severe COVID-19 in kidney transplant recipients during pandemic.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) mRNA vaccination may fail to sufficiently protect transplant recipients against coronavirus disease 2019 (COVID-19). We retrospectively evaluated COVID-19 in kidney transplant recipients (n = 226) after BNT162b2 mRNA vaccine administration. The control group consisted of unvaccinated patients (n = 194) during the previous pandemic wave. We measured anti-spike protein immunoglobulin G (IgG) levels and cellular responses, using enzyme-linked immunosorbent spot assay, in a prospective cohort after vaccination (n = 31) and recovery from COVID-19 (n = 19). COVID-19 was diagnosed in 37 (16%) vaccinated and 43 (22%) unvaccinated patients. COVID-19 severity was similar in both groups, with patients exhibiting a comparable need for hospitalization (41% vs. 40%, p = 1.000) and mortality (14% vs. 9%, p = .726). Short posttransplant periods were associated with COVID-19 after vaccination (p < .001). Only 5 (16%) patients achieved positive SARS-CoV-2 IgG after vaccination, and 17 (89%, p < .001) recovered from COVID-19 (median IgG levels, 0.6 vs. 52.5 AU/ml, p < .001). A cellular response following vaccination was present in the majority (n = 22, 71%), with an increase in interleukin 2 secreting T cells (p < .001). Despite detectable T cell immunity after mRNA vaccination, kidney transplant recipients remained at a high risk of severe COVID-19. Humoral responses induced by vaccination were significantly lower than that after COVID-19.

Substitution of citrate with tissue plasminogen activator (rt-PA) for catheter lock does not improve patency of tunnelled haemodialysis catheters in a randomised trial.

BACKROUND: The study aim was to establish if substitution of citrate with rt-PA for catheter lock once weekly can reduce the incidence of catheter-related blood stream infections (CR-BSI) or improve patency of tunneled haemodialysis catheters. METHODS: All incident patients undergoing insertion of a tunneled haemodialysis catheter were screened and included except those suffering infection or using oral anticoagulation. Study participants were randomized into two arms according to the solution applied as catheter lock: receiving either trisodium citrate (Citra-LockTM 4%) only or rt-PA (Actilyse® 1 mg/ml) on the middle session each week with citrate used on the first and third sessions. The incidence of CR-BSI (confirmed by positive blood culture), catheter non-function (complete obstruction), and malfunction (blood flow < 250 ml/min) was recorded. Statistical significance was tested with ANOVA, post hoc analysis was performed by means of multiple linear regression. RESULTS: Totally, 18 patients were included and followed during 655 haemodialysis sessions. No episode of CR-BSI was detected while 6 catheter non-functions (0.9% sessions) and 101 malfunctions (15.4% sessions) were recorded. The incidence of both events was equal between the study arms: 4 non-functions and 55 malfunctions in the rt-PA arm and 2 non-functions and 46 malfunctions in the citrate arm (p = 0.47 and p = 0.24, respectively). Additionally, the mean blood flow achieved did not differ significantly between the arms: 326 ± 1,8 and 326 ± 1,9 ml/min (p = 0.95) in rt-PA and citrate arms, respectively. Post hoc analysis identified time elapsed since previous session (ß = 0.12, p = 0.005) and malfunction on previous session (ß = 0.25, p < 0.001) as significant factors affecting the occurrence of malfunction. By contrast, the study arm, rt-PA application on previous session, and catheter vintage did not enter the model. CONCLUSION: Substitution of citrate with rt-PA for catheter lock does not reduce the incidence of catheter malfunction neither does it affect the blood flow achieved during haemodialysis. Catheter patency is related rather to the time interval between sessions and to previous malfunction (thus probably reflecting undefined individual factors). The incidence of CR-BSI within pre-selected haemodialysis population is sporadic (less than 1 per 4.3 patient years in our sample). TRIAL REGISTRATION: Australian New Zealand Clinical Trials Registry, ACTRN12612000152820 . Retrospectively registered 03/02/2012.

Cytomegalovirus prevention strategies and the risk of BK polyomavirus viremia and nephropathy.

Polyomavirus BK (BKV) is the cause of polyomavirus-associated nephropathy resulting in premature graft loss. There are limited data regarding the role of cytomegalovirus (CMV) infection and its prevention in developing BKV viremia and PVAN. In a prospective study, we analyzed 207 consecutive renal transplant recipients previously enrolled in 2 randomized trials evaluating different CMV prevention regimens with routine screening for BKV and CMV. Of these, 59 received valganciclovir and 100 valacyclovir prophylaxis; 48 patients were managed by preemptive therapy. At 3 years, the incidence of BKV viremia and PVAN was 28% and 5%, respectively. CMV DNAemia developed in 55% and CMV disease in 6%. Both BKV viremia (42% vs 23% vs 21%, P = .006) and PVAN (12% vs 2% vs 2%, P = .011) were increased in patients treated with valganciclovir prophylaxis compared to valacyclovir and preemptive therapy. Using multivariate Cox proportional hazard regression, valganciclovir prophylaxis was independent predictor of BKV viremia (hazard ratio [HR] = 2.38, P = .002) and PVAN (HR = 4.73, P = .026). In contrast, the risk of subsequent BKV viremia was lower in patients with antecedent CMV DNAemia (HR = 0.50, P = .018). These data suggest valganciclovir prophylaxis may be associated with increased risk of BKV viremia and PVAN. CMV DNAemia did not represent a risk for BKV.

Viral load and duration of BK polyomavirus viraemia determine renal graft fibrosis progression: histologic evaluation of late protocol biopsies.

BACKGROUND: Polyomavirus BK (BKV) infection of the renal allograft causes destructive tissue injury with inflammation and subsequent fibrosis. METHODS: Using a prospective cohort of patients after kidney transplantation performed between 2003 and 2012, we investigated the role of BKV viraemia in the development and progression of interstitial fibrosis and tubular atrophy (IFTA). The primary outcome was moderate-to-severe IFTA assessed by protocol biopsy at 36 months. RESULTS: A total of 207 consecutive recipients were enrolled. Of these, 57 (28%) developed BKV viraemia with 10 (5%) cases of polyomavirus-associated nephropathy (PVAN). Transient (<3 months) BKV viraemia occurred in 70% of patients, and persistent (≥3 months) BKV viraemia in 30%. A high viral load (≥10 000 copies/mL) was detected in 18% and a low viral load (<10 000 copies/mL) in 61%, while the viral load could not be determined in 21%. Moderate-to-severe IFTA was significantly increased in high [71%; odds ratio (OR) = 12.1; 95% confidence interval (CI) 1.62-90.0; P = 0.015] or persistent BKV viraemia (67%; OR = 6.33; 95% CI 1.19-33.7; P = 0.031) with corresponding rise in 'interstitial fibrosis + tubular atrophy' scores. Only patients with transient low BKV viraemia showed similar incidence and progression of IFTA to the no-BKV group. Persistent low BKV viraemia was uncommon yet the progression of fibrosis was significant. Only recipients with PVAN experienced inferior graft survival at 5 years. CONCLUSIONS: These data suggest that only transient low BKV viraemia does not negatively affect the progression of allograft fibrosis in contrast to excessive risk of severe fibrosis after high or persistent BKV viraemia.

Less renal allograft fibrosis with valganciclovir prophylaxis for cytomegalovirus compared to high-dose valacyclovir: a parallel group, open-label, randomized controlled trial.

BACKGROUND: Cytomegalovirus (CMV) prophylaxis may prevent CMV indirect effects in renal transplant recipients. This study aimed to compare the efficacy of valganciclovir and valacyclovir prophylaxis for CMV after renal transplantation with the focus on chronic histologic damage within the graft. METHODS: From November 2007 through April 2012, adult renal transplant recipients were randomized, in an open-label, single-center study, at a 1:1 ratio to 3-month prophylaxis with valganciclovir (n = 60) or valacyclovir (n = 59). The primary endpoint was moderate-to-severe interstitial fibrosis and tubular atrophy assessed by protocol biopsy at 3 years evaluated by a single pathologist blinded to the study group. The analysis was conducted in an intention-to-treat population. RESULTS: Among the 101 patients who had a protocol biopsy specimen available, the risk of moderate-to-severe interstitial fibrosis and tubular atrophy was significantly lower in those treated with valganciclovir (22% versus 34%; adjusted odds ratio, 0.31; 95% confidence interval, 0.11-0.90; P = 0.032 by multivariate logistic regression). The incidence of CMV disease (9% versus 2%; P = 0.115) and CMV DNAemia (36% versus 42%; P = 0.361) were not different at 3 years. CONCLUSIONS: Valganciclovir prophylaxis, as compared with valacyclovir, was associated with a reduced risk of moderate-to-severe interstitial fibrosis and tubular atrophy in patients after renal transplantation. TRIAL REGISTRATION: Australian New Zealand Clinical Trials Registry ( ACTRN12610000016033 ). Registered on September 26, 2007.

[Cytomegalovirus and polyomavirus infection after renal transplantation]. / Cytomegalovirová a polyomavirová infekce po transplantaci ledviny.

Viral infections are among the most common infectious complications affecting transplant recipients. Due to immunosuppressive therapy predominantly affecting cellular immunity and thus successfully reducing the incidence of acute rejection, there is a higher incidence of viral infections. Herpesviruses and polyomaviruses are ubiquitous pathogens which have the ability to persist in a state of latent infection. In addition to post-transplant reactivation, donor-induced primoinfection can also occur, leading to increased morbidity and contributing to decreased survival of patients. Moreover, there are long-term indirect effects, resulting in an impaired function of the transplanted organs and their premature loss. This article provides a brief overview of infections which have the greatest impact on transplant recipients, i.e. cytomegalovirus and BK polyomavirus, their diagnosis, prevention and treatment.Key words: BK virus - cytomegalovirus - ganciclovir - immunosuppressive therapy - JC virus - kidney transplantation - polyomavirus - polyomavirus-associated nephropathy - preemptive therapy - prophylaxis - valaciclovir.

The impact of viral load and time to onset of cytomegalovirus replication on long-term graft survival after kidney transplantation.

BACKGROUND: Asymptomatic cytomegalovirus (CMV) infection is associated with graft dysfunction and failure. However, no study assessed CMV viral load in terms of the risk for graft failure. METHODS: In a prospective cohort of kidney transplant recipients, we assessed the impact of CMV DNAemia on the overall graft survival and the incidence of moderate-to-severe interstitial fibrosis and tubular atrophy (IF/TA) in protocol biopsy at 36 months. CMV DNAemia was stratified by viral load in whole blood. RESULTS: A total of 180 patients transplanted from October 2003 through January 2011 were included and followed for 4 years; 87 (48%) patients received 3-month prophylaxis with valacyclovir and 45 (25%) with valganciclovir; 48 (27%) were managed by pre-emptive therapy. Within 12 months of transplantation, CMV DNAemia developed in 102 (57%) patients with 36 (20%) having a viral load of ≥2,000 copies/ml. Multivariate Cox analysis identified CMV DNAemia as an independent risk factor for graft loss (hazard ratio 3.42; P=0.020); however, after stratification by viral load, only CMV DNAemia ≥2,000 copies/ml (hazard ratio 7.62; P<0.001) remained significant. Both early-onset (<3 months; P=0.048) and late-onset (>3 months; P<0.001) CMV DNAemia ≥2,000 copies/ml were risk factors for graft loss. The incidence of moderate-to-severe IF/TA was not significantly influenced by CMV DNAemia. CONCLUSIONS: Kidney transplant recipients having CMV DNAemia with a higher viral load irrespective of the time to onset are at increased risk for graft loss.

[Pros and cons of dual kidney transplantation]. / Klady a rizika duální transplantace ledvin.

Dual kidney transplantation is one of the options to utilize so called marginal grafts, kidneys that would be insufficient for normal single transplantation. This time consuming and burdensome surgical procedure can be beneficial in precisely selected patients. This method requires correct algorithm of donors and recipients selections, than we can expect the best results.Key words: dual kidney transplantation, marginal donor, chronic renal failure, expanded criteria donor.

Citrate-Buffered Dialysis Solution (Citrasate) Allows Avoidance of Anticoagulation During Intermittent Hemodiafiltration-At the Cost of Decreased Performance and Systemic Biocompatibility.

Reportedly, citrate-based dialysis solution enables heparin dose tapering or even complete exclusion, particularly in postdilution hemodiafiltration (HDF). The aim of the study was to verify this strategy in predilution setting and to assess its short-term safety, efficacy, and biocompatibility. Ten regular hemodialysis patients were assigned to predilution HDF on acetate- and citrate-based dialysis solutions (0.8 mmol/l trisodium citrate) at random order. Acetate HDF was performed using routine dose of heparin while citrate HDF was heparin free. Plasma calcium, thrombin-antithrombin complexes (TAT), and citrate levels were measured at 0, 30, 60, 120, and 240 min. Following each session, a semiquantitative dialyzer clotting score (DCT 1-5) was assessed and HDF adequacy was determined as spKt/V. Statistical relevance was tested by ANOVA with pP < 0.05 held significant, data are given as means ± standard deviations. All sessions were accomplished successfully, premature termination or circuit re-setting was not necessary. However, DCT was significantly higher in citrate-HDF compared to acetate-HDF regimen (3.4 ± 0.65 and 1.8 ± 0.79, respectively, P = 0.002) as well as TAT generation rate (increase per session by factor 11.0 ± 8.43 and 2.1 ± 1.26, respectively, P = 0.004 between regimens). Ionized calcium declined only by the end of citrate-HDF (from 1.09 ± 0.086 to 0.99 ± 0.030 mmol/L, P = 0.002) yet without accompanying clinical symptoms. Systemic citrate levels increased along the citrate-HDF session but stayed an order of magnitude below concentrations needed to establish citrate anticoagulation (peak at 0.276 ± 0.112 mmol/L). Dialysis adequacy estimated by spKt/V was found lower in citrate-HDF vs. acetate-HDF (1.48 ± 0.163 and 1.58 ± 0.165, respectively, P = 0.006). Although predilution HDF using citrate-based dialysate is feasible without heparin, both dialysis adequacy and biocompatibility is significantly compromised. Therefore, this approach can be adopted for a single procedure but is not acceptable on a regular basis.

The DESCARTES-Nantes survey of kidney transplant recipients displaying clinical operational tolerance identifies 35 new tolerant patients and 34 almost tolerant patients.

BACKGROUND: Kidney recipients maintaining a prolonged allograft survival in the absence of immunosuppressive drugs and without evidence of rejection are supposed to be exceptional. The ERA-EDTA-DESCARTES working group together with Nantes University launched a European-wide survey to identify new patients, describe them and estimate their frequency for the first time. METHODS: Seventeen coordinators distributed a questionnaire in 256 transplant centres and 28 countries in order to report as many 'operationally tolerant' patients (TOL; defined as having a serum creatinine <1.7 mg/dL and proteinuria <1 g/day or g/g creatinine despite at least 1 year without any immunosuppressive drug) and 'almost tolerant' patients (minimally immunosuppressed patients (MIS) receiving low-dose steroids) as possible. We reported their number and the total number of kidney transplants performed at each centre to calculate their frequency. RESULTS: One hundred and forty-seven questionnaires were returned and we identified 66 TOL (61 with complete data) and 34 MIS patients. Of the 61 TOL patients, 26 were previously described by the Nantes group and 35 new patients are presented here. Most of them were noncompliant patients. At data collection, 31/35 patients were alive and 22/31 still operationally tolerant. For the remaining 9/31, 2 were restarted on immunosuppressive drugs and 7 had rising creatinine of whom 3 resumed dialysis. Considering all patients, 10-year death-censored graft survival post-immunosuppression weaning reached 85% in TOL patients and 100% in MIS patients. With 218 913 kidney recipients surveyed, cumulative incidences of operational tolerance and almost tolerance were estimated at 3 and 1.5 per 10 000 kidney recipients, respectively. CONCLUSIONS: In kidney transplantation, operational tolerance and almost tolerance are infrequent findings associated with excellent long-term death-censored graft survival.

Randomized trial of valganciclovir versus valacyclovir prophylaxis for prevention of cytomegalovirus in renal transplantation.

BACKGROUND AND OBJECTIVES: Both valganciclovir and high-dose valacyclovir are recommended for cytomegalovirus prophylaxis after renal transplantation. A head-to-head comparison of both regimens is lacking. The objective of the study was to compare valacyclovir prophylaxis with valganciclovir, which constituted the control group. DESIGN, SETTINGS, PARTICIPANTS, & MEASUREMENTS: In a randomized, open-label, single-center trial, recipients of renal transplants (recipient or donor cytomegalovirus-seropositive) were randomly allocated (1:1) to 3-month prophylaxis with valacyclovir (2 g four times daily) or valganciclovir (900 mg daily). Enrollment occurred from November of 2007 to April of 2012. The primary end points were cytomegalovirus DNAemia and biopsy-proven acute rejection at 12 months. Analysis was by intention to treat. RESULTS: In total, 119 patients were assigned to valacyclovir (n=59) or valganciclovir prophylaxis (n=60). Cytomegalovirus DNAemia developed in 24 (43%) of 59 patients in the valacyclovir group and 18 (31%) of 60 patients in the valganciclovir group (adjusted hazard ratio, 1.35; 95% confidence interval, 0.71 to 2.54; P=0.36). The incidence of cytomegalovirus disease was 2% with valacyclovir and 5% with valganciclovir prophylaxis (adjusted hazard ratio, 0.21; 95% confidence interval, 0.01 to 5.90; P=0.36). Significantly more patients with valacyclovir prophylaxis developed biopsy-proven acute rejection (18 of 59 [31%] versus 10 of 60 [17%]; adjusted hazard ratio, 2.49; 95% confidence interval, 1.09 to 5.65; P=0.03). The incidence of polyomavirus viremia was higher in the valganciclovir group (18% versus 36%; adjusted hazard ratio, 0.43; 95% confidence interval, 0.19 to 0.96; P=0.04). CONCLUSIONS: Valganciclovir shows no superior efficacy in cytomegalovirus DNAemia prevention compared with valacyclovir prophylaxis. However, the risk of biopsy-proven acute rejection is higher with valacyclovir.

The efficacy and cost-effectiveness of valacyclovir in cytomegalovirus prevention in solid organ transplantation.

Prevention of cytomegalovirus infection using antiviral prophylaxis or the pre-emptive therapy approach is an integral part of management of patients after solid organ transplantation. Regarding renal transplantation, valacyclovir is currently the only antiviral agent recommended for prophylaxis as an alternative to valganciclovir. This review article discusses studies documenting the efficacy and safety of valacyclovir prophylaxis as well as those comparing valacyclovir with other prophylactic regimens or with pre-emptive therapy. Also addressed are the economic aspects supporting the cost-effectiveness of valacyclovir prophylaxis and demonstrating lower costs compared with other cytomegalovirus preventive strategies.

Long-term outcomes of pre-emptive valganciclovir compared with valacyclovir prophylaxis for prevention of cytomegalovirus in renal transplantation.

Prevention of cytomegalovirus (CMV) is essential in organ transplantation. The two main strategies are pre-emptive therapy, in which one screens for and treats asymptomatic CMV viremia, and universal antiviral prophylaxis. We compared these strategies and examined long-term outcomes in a randomized, open-label, single-center trial. We randomly assigned 70 renal transplant recipients (CMV-seropositive recipient or donor) to 3-month prophylaxis with valacyclovir (n=34) or pre-emptive valganciclovir for significant CMV viremia detected at predefined assessments through month 12 (n=36). Among the 55 patients who had a protocol biopsy specimen available at 3 years to allow assessment of the primary outcome, 9 (38%) of 24 patients in the prophylaxis group and 6 (19%) of 31 patients in the pre-emptive therapy group had moderate to severe interstitial fibrosis and tubular atrophy (odds ratio, 2.50; 95% confidence interval, 0.74-8.43; P=0.22). The prophylaxis group had significantly higher intrarenal mRNA expression of genes involved in fibrogenesis. The occurrence of CMV disease was similar in both groups, but pre-emptive therapy improved 4-year graft survival (92% versus 74%; P=0.049) as a result of worse outcomes in patients with late-onset CMV viremia. In conclusion, compared with valacyclovir prophylaxis, pre-emptive valganciclovir therapy may lead to less severe interstitial fibrosis and tubular atrophy and to significantly better graft survival.

Pharmacoeconomic impact of different regimens to prevent cytomegalovirus infection in renal transplant recipients.

BACKGROUND: The aim of this study was to determine the cost impact of four different strategies for prevention of cytomegalovirus (CMV) disease after renal transplantation. METHODS: Hospitalization data and medical resource utilization data were prospectively collected alongside two randomized trials. In the first trial, the patients were randomized to 3-month prophylaxis with either oral ganciclovir (1 g t.i.d., n = 36) or valacyclovir (2 g q.i.d., n = 35), and to the control group (n = 12) managed by deferred therapy. In the second trial, the patients were randomly assigned to 3-month valacyclovir prophylaxis (n = 34) or preemptive therapy with valganciclovir (900 mg b.i.d. for a minimum of 14 days, n = 36) for significant CMV DNAemia. The cost analysis involved all real costs directly related to CMV during the first year after renal transplantation. RESULTS: The mean CMV-associated costs per patient were EUR 4,581, 2,577, 4,968, and 8,050 in patients in the ganciclovir, valacyclovir, preemptive, and deferred therapy groups, respectively (p < 0.001). Valacyclovir prophylaxis was significantly less expensive than any other regimen. The cost of one episode of CMV disease was EUR 7,510 per patient. Due to excessive incidence of CMV disease, deferred therapy was the most expensive strategy (p < 0.001). CONCLUSIONS: Valacyclovir prophylaxis is less expensive strategy compared with any other regimen.

Advances in cytomegalovirus-preventive strategies in solid organ transplantation: defending pre-emptive therapy.

Prevention of cytomegalovirus (CMV) infection is an important part of clinical care provided to patients after solid organ transplantation. While the optimal preventive strategy has not been defined, most centers rely on universal prophylaxis or pre-emptive therapy. This article comments on recent studies designed to identify strategies that effectively reduce the incidence of late-onset CMV disease as the main problem associated with prophylaxis, and on recent data regarding the development of CMV-specific immunity depending on the CMV-preventive regimen used. Despite an apparent trend to prefer prophylaxis in clinical practice, this approach does not seem to be based on robust evidence.

Evaluation of three different methods to prevent dialyzer clotting without causing systemic anticoagulation effect.

Thrombogenicity is one of the most important biocompatibility markers of artificial material. Anticoagulation is commonly used to reduce thrombogenicity of the extracorporeal circuit (ECC) during intermittent hemodialysis (IHD). In some situations, systemic anticoagulants are contraindicated. The aim of our study was to compare thrombogenicity parameters during IHD with three different methods without a systemic anticoagulation effect. In a prospective, randomized, and crossover study, we examined 10 stable patients during IHD with (i) regular saline flushes of ECC; (ii) regional citrate anticoagulation (RCA); and (iii) AN69 ST membrane after ECC priming according to the manufacturer's recommendations. Before IHD and after 10, 60, 120, and 240 min, we measured the platelet count and the plasma concentrations of platelet factor 4 (PF4) and thrombin/antithrombin complexes (TAT). All 10 procedures with RCA were successfully completed after 4 h, whereas 6/10 procedures with saline flushes and 5/10 procedures with AN69 ST were finished prematurely because of clotting (P < 0.05). The TAT production was significantly increased during saline flushes and AN69 ST compared with RCA (P < 0.05). Platelet activation demonstrated by rising PF4 was present during all three methods. Markers of coagulation cascade activation were progressively increasing during IHD with RCA, saline flushes, and AN69 ST. The activation was significantly lower during RCA, and according to thrombogenicity, RCA is the most effective among compared anticoagulation methods.