Search

More than 2 years after the pandemic, the availability of vaccination and the use of monoclonal antibodies and direct antivirals have changed the fate of COVID-19, allowing for a better management of the disease, reducing hospitalization rates, and improving survival. This study aims to describe the outcome of COVID-19 in a cohort of solid organ transplant recipients and the impact of novel antivirals against SARS-CoV-2. We conducted an observational retrospective cohort study. We enrolled solid organ transplant recipients with COVID-19 attending the A.O.U. Federico II of Naples and followed up from January 2022 to July 2022. We enrolled 40 SOTs with COVID-19. Our experience highlights the favorable impact of therapies with antivirals and monoclonal antibodies in the early stages of COVID-19. Interesting data concern the impact of immunosuppressive therapy on COVID-19, in particular the role of Mycophenolate (associated with deterioration to severe COVID-19) and Everolimus (protective for progression to severe disease) needs to be investigated. Our experience also confirms the fundamental role of vaccination and in particular the importance of the booster dose.

Background In kidney transplant recipients (KTR), the end-stage kidney disease (ESKD) risk dependent on the risk factors acting in native chronic kidney disease (CKD) remains undefined. Methods We compared risk and determinants of ESKD between 757 adult KTR and 1940 patients with native CKD before and after propensity-score (PS) analysis matched for unmodifiable risk factors [(age, sex, diabetes, cardiovascular disease and estimated glomerular filtration rate (eGFR)]. Results In unmatched cohorts, eGFR was lower in CKD versus KTR (45.9 ± 11.3 versus 59.2 ± 13.4 mL/min/1.73 m2, P < 0.001). During a median follow-up of 5.4 years, the unadjusted cumulative incidence of ESKD was consistently lower in unmatched KTR versus CKD. Conversely, in PS-matched analysis, the risk of ESKD in KTR was 78% lower versus CKD at 1 year of follow-up while progressively increased over time resulting similar to that of native CKD patients after 5 years and 2.3-fold higher than that observed in CKD at 10 years. R2 analysis in unmatched patients showed that the proportion of the outcome variance explained by traditional ESKD determinants was smaller in KTR versus native CKD (31% versus 70%). After PS matching, the risk of ESKD [hazard ratio (HR), 95% confidence interval (95% CI)] was significantly associated with systolic blood pressure (1.02, 1.01–1.02), phosphorus (1.31, 1.05–1.64), 24-h proteinuria (1.11, 1.05–1.17) and haemoglobin (0.85, 0.78–0.93) irrespective of KTR status. Similar data were obtained after matching also for modifiable risk factors. Conclusions In KTR, when compared with matched native CKD patients, the risk of ESKD is lower in the first 5 years and higher later on. Traditional determinants of ESKD account for one-third of the variability of time-to-graft failure.

Vaccination against SARS-CoV2 represents a key weapon to prevent COVID-19, but lower response rates to vaccination have frequently been reported in solid organ transplant recipients. The aim of our study was to evaluate the rate of seroconversion to SARS-CoV-2 mRNA vaccines in a cohort of kidney transplant recipients and the potential role of the different immunosuppressive regimens. We conducted an observational retrospective cohort study in kidney transplant patients vaccinated for COVID-19. For each patient, we evaluated IgG anti-S-RBD SARS-CoV-2 titers immediately before the administration of first COVID-19 vaccination dose, 20 days after the first dose and 40 days after the second dose. Moreover, we evaluated the type of immunosuppressive treatment and the incidence of vaccine breakthrough SARS-CoV-2 infection. We enrolled 121 kidney transplant patients vaccinated for COVID-19. At the time of administration of the first vaccine dose, all patients had a negative antibody titer; only 4.1% had positive antibody titers 20 days after the first dose. More than half patients 62 (51%) had protective antibody titers 40 days after the second dose. A total of 18 Solid Organ Transplant Recipients (SOTRs) (14.9%) got a SARS-CoV-2 breakthrough infection during the study period. With regard to immunosuppressive regimen, patients on mycophenolate-based regimen (48.7%) showed the lowest antibody response rates (27.5%) compared to other regimens. Our study confirms that kidney transplant patients show a poor response to two doses of COVID-19 vaccination. Moreover, in our study the use of mycophenolate is significantly associated with a non-response to COVID-19 m-RNA vaccines.

Proteinuria represents an increase in the urinary excretion of proteins. It could also follow kidney transplantation and affects more than 40% of kidney transplant patients per year. It results from protein increases in their filtered load, due to alterations in the selectivity of the glomerular capillary wall, or from defects in their tubular uptake. Different parameters are associated with the various stages of proteinuria and therefore allow characterizing of its severity. For this purpose, the variation of proteinuria was evaluated by loading input two parameters: glycemia and the blood level of the m-Tor inhibitor. Through combination of data with different machine learning algorithms, the goal of this research work was to evaluate how blood glucose values and the use of immunosuppressive drugs can lead to prediction proteinuria classification in patients.

Background The effects of kidney transplantation on male sexual function are controversial. Aim To evaluate the impact of kidney transplantation on erectile and ejaculatory function and to assess a possible correlation between some selected characteristics of patients and their erectile and ejaculatory function after renal transplantation. Methods An observational retrospective analysis was conducted on male patients who had undergone kidney transplantation from January 2009 to April 2019. A prospectively maintained database was used to collect all data. Patients were evaluated before kidney transplant and 6 and 12 months after kidney transplant. Male patients undergoing renal transplantation for any cause who were sexually active with a stable partner were included in the study. Outcomes The main outcome measures included the International Index of Erectile Function (IIEF-15) and the 4-item version of Male Sexual Health Quality–Ejaculation Disorders (MSHQ-EjD Short Form) questionnaires. The first 3 questions of the MSHQ-EjD Short Form were used to assess the ejaculatory function, whereas the fourth question was used to evaluate the ejaculation bother. Results A total of 95 patients were eligible in the study. The evaluation of sexual function was available in 56 patients (58.9%). Mean IIEF-15 significantly decreased at 6 months (P Clinical Implications Improvement of knowledge regarding the effects of kidney transplantation on sexual function and about the patient characteristics related to sexual health after transplantation. Strength & Limitations This is the first article that analyzes in depth the ejaculatory function in patients who had undergone kidney transplantation assessing ejaculation with a validated questionnaire. The main limitation is the retrospective design of the study. Conclusion Kidney transplantation appears to have a negative impact on sexual health, significantly worsening both erectile and ejaculatory functions. Age, diabetes, hypertension, smoking, pretransplantation testosterone levels, time for transplantation, as well as erectile and ejaculatory function before transplant were significantly related to erectile and ejaculatory functions after renal transplantation.

Kidney transplantation is the surgical operation by which one of the two original kidneys is replaced with another healthy one donated by a compatible individual. In most cases, donors are recently deceased. There is the possibility of withdrawing a kidney from a consenting living subject. Usually, living donors are direct family members, but they could be volunteers completely unrelated to the recipient. A much-feared complication in case of kidney transplantation is the appearance of infections. These tend to arise due to immune-suppressor drugs administered as anti-rejection therapy. In this review, we describe the gastrointestinal complications that can occur in subjects undergoing renal transplantation associated with secondary pathogenic microorganisms or due to mechanical injury during surgery or to metabolic or organic toxicity correlated to anti-rejection therapy. Some of these complications may compromise the quality of life or pose a significant risk of mortality; fortunately, many of them can be prevented and treated without the stopping the immunosuppression, thus avoiding the patient being exposed to the risk of rejection episodes., Graphical abstract

Background: Rocuronium can be used in patients with severe renal failure (creatinine clearance

Background Rocuronium can be used in patients with severe renal failure (creatinine clearance

INTRODUZIONE: Il rene trapiantato è esposto agli effetti dell’ischemia-riperfusione responsabili di ritardata ripresa funzionale dell’organo (delayed graft function; DGF). DGF può incidere negativamente sull’evoluzione del rene trapiantato. Nel presente studio è stato valutato il ruolo della lipocalina urinaria quale predittore di DGF. MATERIALI E METODI: Sono stati valutati pazienti sottoposti a trapianto di rene da donatore cadavere. Prelievi ematici erano effettuati immediatamente prima del trapianto. Le urine erano raccolte per le 24 ore successive al trapianto. DGF era definita dalla necessità di trattamento dialitico entro la prima settimana dal trapianto. RISULTATI: Sono stati valutati 20 pazienti. I pazienti che avevano una rapida ripresa funzionale del rene trapiantato (NO-DGF) erano 14 (70%). DGF era osservata in 6 pazienti. L’età media nei DGF era superiore (58±6 Vs 51±11, p=0.001). Nei pazienti DGF risultavano significativamente ridotta la diuresi (57±35 Vs 4150 ± 2230 ml/24h; p=0.001) e la escrezione urinaria di creatinina (191±184 Vs 683±660 mg/24h; p=0.001), misurate nel primo giorno successivo al trapianto. Non erano osservate significative differenze tra pazienti DGF e NO-DGF per la escrezione urinaria di lipocalina (1,20±2,20 Vs 2,44±4,0 mg/24h; p

Background Tacrolimus (TCR) is an immunosuppressive drug used by oral administration. Intravenous (IV) TCR administration is required under conditions of gastrointestinal diseases or abdominal surgery at the onset of paralytic ileus. The infusion formulation needs a large dilution and therefore a careful technical management during continuous infusion by 24 h and may determine anaphylaxis, cardiac arrhythmia, QT prolongation and torsades de pointes. Sublingual (SL) TCR administration was suggested as an alternative route. Design The aim of this study was to compare in the same kidney transplanted patients the TCR pharmacokinetic profiles by both the routes coupled with the pharmacoeconomic analysis. The study enrolled eight subjects undergoing renal transplantation and treated with TCR and methylprednisolone. TCR was administered by oral route at the scheduled dosage while the 50% of oral dosage was used by SL route, taking into account the absence of liver first pass. Results Except for AUC, which resulted significantly increased after oral administration, all exposure parameters were not significantly different between the two routes of administration. Analysis of dose-adjusted exposure parameters showed significant increases in AUC and Cmin after SL administration confirming a better bioavailability of the SL route compared with oral route. Cost saving was obtained using the SL rather than the IV route of TCR delivery. Conclusion When oral administration of TCR is not advised, SL delivery represents an attractive option to IV administration.

Kidney transplantation is frequently complicated by delayed graft function (DGF). DGF is associated with more frequent rejection episodes, increased need of post-transplantation biopsies, dialysis sessions and prolonged hospitalization. These complications may have negative impact on long-term survival of transplanted kidney.Urinary neutrophil gelatinase-associated lipocalin (uNGAL) is regarded as acute kidney injury marker.This preliminary study aimed at evaluating whether uNGAL may be early predictor of DGF in kidney transplanted patients.Urine samples were collected from renal transplant recipients on day 1 post-transplantation to determine 24/h urinary NGAL and creatinine excretion. On same day, routine blood chemistry was assessed.N. 20 renal transplant recipients were evaluated. DGF was observed in n. 6 patients (DGF-patients). In DGF-patients compared to NO-DGF-patients, mean age was higher (586 Vs 5111, p=0.001), while 24/h urine output (5735 Vs 4150 2230 ml/24h; p=0.001) and urinary creatinine excretion (191184 Vs 683660 mg/24h; p=0.001) were lower. No difference was found between DGF- and NO-DGF-patients in 24/h urinary NGAL excretion (1,202,20 Vs 2,444,0 mg/24h; p0.20). In univariate analysis, DGF was inversely associated to 24/h urine output (r2=-0.795, p=0.001) and urinary creatinine excretion (r2=-0.480, p=0.037) and positively to age (r2=0.446, p=0.049). In multivariate analysis 24/h urine output (p=0.014) and 24/h urinary creatinine excretion (p=0.039) were associated to DGF.This preliminary study suggests that 24/h urinary NGAL excretion, measured 1 day after kidney transplantation, is not a reliable predictor of DGF. Larger study with longer observation period is mandatory.

BACKGROUND: Renal transplantation (RT) is the most common solid organ transplant procedure. Several studies have reported on gonadal function in male and female RT recipients with controversial results. METHODS: Forty consecutive patients (20 male, 20 female) with a fully functioning allograft (serum creatinine 0.8-1.3 mg/dl) for at least 15 months after RT were included in the study. Their ages ranged from 23 to 44 years (median 38) and their post-RT follow-up lasted 15-86 months (median 23). FSH, LH, prolactin, 17-beta-estradiol, testosterone, androstenedione and dehydroepiandrostrone were determined in all patients and compared with a group of 80 healthy subjects. Pelvic ultrasonography was performed in all participants. RESULTS: Testosterone was below the normal range in 70% of male patients and within the lowest third in the remainder; a lack of LH increase indicated an inhibition of the reproductive axis. Male testosterone values were negatively influenced by calcineurine inhibitors treatment (P < 0.005), but positively influenced by a better graft function (P < 0.0001). Testicular and prostate volumes were reduced with respect to controls, with the latter related to circulating testosterone levels. Ten of the women (50%) had menstrual cycle disorders after RT, three being affected by transient, and three by persistent, amenorrhea. Another two patients had had transient polymenorrhea. In four women (20%), a premature ovarian failure was diagnosed. No relationship was found between female reproductive function and age, graft function or duration of the post-transplant period. Prolactin was lower in patients on calcineurin inhibitors (P < 0.01). CONCLUSIONS: Abnormalities of the reproductive system were frequent after successful RT in both genders.

Introduction This study aims to investigate possible risk factors for diverticulitis in kidney transplant recipients affected by colonic diverticulosis. Methods and Results We investigated 717 patients transplanted between 2000 and 2010. Diverticular disease was endoscopically diagnosed in 17 of 717 examined patients. Eight patients were diagnosed with autosomal dominant polycystic kidney disease (ADPKD); 9 of 17 patients underwent emergency surgery. We performed Hartmann's procedure on all patients, with a second stage performed at least 6 months later. Discussion Although the incidence of colonic diverticular perforation in kidney transplanted patients is similar to that observed in the general population, perforation in immunosuppressed patients is associated with a higher morbidity/mortality rate. In our study, the incidence of perforation is 1.25% (9 of 717), with almost half of the cases observed in patients with ADPKD (4 of 9). Such an observation is consistent with published data, in which patients with ADPKD are reported to more frequently develop colonic diverticulosis and its complications. One possible explanation might be related to a belated diagnosis of diverticulitis, which could initially simulate an inflammatory disease as a consequence of renal cysts. Also, steroids seem to be a predisposing factor for colonic perforation in these patients. Conclusions A timely surgery can significantly reduce mortality. In cases of elective surgery, mortality and morbidity are similar to those of immunocompetent patients; accordingly, this is the goal to be pursued. Early signs and symptoms are often masked by immunosuppressive therapy. In these patients, surgeons should always perform (1) abdominal computed tomography scanning and, in the presence of diverticulitis, reduce or withdraw immunosuppressive therapy; and (2) early surgery, with Hartmann's procedure being, in our opinion, the best choice. Before transplantation, elective surgery for colonic resection should be considered in patients with ADPKD or with a history of 1 or more episodes of acute diverticulitis who then regressed with medical therapy.

Massimo Sabbatini,1 Gianluca Garofalo,1 Silvio Borrelli,2 Sossio Vitale,1 Massimiliano Torino,1 Domenico Capone,3 Luigi Russo,3 Antonio Pisani,1 Rosa Carrano,1 Riccardo Gallo,1 Stefano Federico11Nephrology, Department of Public Health, University Federico II of Naples, 2Department of Nephrology, Second University of Naples, 3Department of Neurosciences, Unit of Clinical Pharmacology, University Federico II of Naples, Naples, ItalyPurpose: The aim of this study was to determine the prevalence of nonadherence in a cohort of renal transplant recipients (RTRs) and to evaluate prospectively whether more intense clinical surveillance and reduced pill number enhanced adherence.Patients and methods: The study was carried out in 310 stable RTRs in whom adherence, life satisfaction, and transplant care were evaluated by specific questionnaires (time 0). The patients under tacrolimus (TAC; bis in die [BID]) were then shifted to once-daily TAC (D-TAC) to reduce their pill burden (Shift group) and were followed up for 6 months to reevaluate the same parameters. Patients on cyclosporin or still on BID-TAC constituted a time-control group.Results: The prevalence of nonadherence was 23.5% and was associated with previous rejection episodes (P

This study investigates the potential pharmacokinetic interactions between an antimicrobial agent, moxifloxacin, and 2 immunosuppressant drugs, cyclosporine and tacrolimus, in kidney transplant recipients. Twenty-two kidney transplant patients needing antibiotic therapy for urinary tract infections are enrolled. Eleven patients are under cyclosporine treatment and the other 11 patients are under tacrolimus treatment. Because the urinary tract infections are caused by gram-negative aerobes sensitive to moxifloxacin, this antibiotic is administered by oral route at a dose of 400 mg/d for 1 week; in each patient pharmacokinetic studies are carried out before and at the seventh day of therapy. For both immunosuppressors, none of the pharmacokinetic parameters investigated show statistically significant differences between values obtained before and during treatment with moxifloxacin. In fact, the concentration-time profiles of monoclonal cyclosporine, polyclonal cyclosporine, and tacrolimus are not significantly different before and during the antimicrobial therapy. The results of the present study rule out interference of moxifloxacin with both cyclosporine and tacrolimus kinetics and indicate that the concomitant administration of the fluoroquinolone and cyclosporine or tacrolimus does not require modifications of the dosages of 2 immunosuppressant drugs.

BACKGROUND AND OBJECTIVE: Bacterial infections are common complications after organ transplantation. Fluoroquinolones are frequently used for treatment because of their broad spectrum of activity; but some of them, such as ciprofloxacin and norfloxacin, are reported to increase blood concentration of ciclosporin because they are metabolised by the liver through the same enzymatic pathway, the cytochrome P450 system. This study was performed to establish whether levofloxacin, a more recent fluoroquinolone that undergoes limited hepatic metabolism, interferes with metabolism and excretion of either ciclosporin microemulsion or tacrolimus. METHODS: Pharmacokinetic studies were carried out in two groups of renal transplant patients, on either ciclosporin or tacrolimus treatment, before and at the sixth day of treatment with levofloxacin. RESULTS: Levofloxacin significantly increased the mean area under the blood concentration-time curve (AUC) and the other pharmacokinetic parameters of ciclosporin and tacrolimus by about 25%. The interference of levofloxacin on the hepatic metabolism of these drugs was demonstrated by the concomitant decrease by 5% of polyclonal ciclosporin concentration, which is the expression of parent drug and its metabolites. Both before and during levofloxacin treatment we observed trough concentrations of monoclonal and polyclonal ciclosporin significantly lower in the evening (C(12)) than in the morning (C(0)); this observation suggests a circadian variation in the metabolism of this drug. However, no difference between C(0) and C(12) was observed with tacrolimus, confirming its more predictable bioavailability. CONCLUSION: Our data demonstrate that levofloxacin partially inhibits the metabolism of both ciclosporin microemulsion and tacrolimus, and therefore close therapeutic monitoring of these two drugs should be recommended during levofloxacin therapy.