Do Infectious Diseases After Kidney Retransplantation Differ From Those After First Kidney Transplantation?

Background: Infectious diseases (IDs) are highly relevant after solid organ transplantation in terms of morbidity and mortality, being among the most common causes of death. Patients undergoing kidney retransplantation (re-K-Tx) have been already receiving immunosuppressive therapy over a prolonged period, potentially facilitating subsequent infections. Comparing ID events after re-K-Tx and first kidney transplantation (f-K-Tx) can delineate patterns and risks of ID events associated with prolonged immunosuppression. Methods: We included adult patients with records on f-K-Tx and re-K-Tx in the Swiss Transplant Cohort Study. We analyzed ID events after f-K-Tx and re-K-Tx within the same patients and compared infection rates, causative pathogens, and infection sites. Recurrent time-to-event analyses were performed for comparison of infection rates. Results: A total of 59 patients with a median age of 47 years (range, 18-73) were included. Overall, 312 ID events in 52 patients occurred. In multivariable recurrent event modeling, the rate of ID events was significantly lower after re-K-Tx (hazard ratio, 0.70; P = .02). More bacterial (68.9% vs 60.4%) and fungal (4.0% vs 1.1%) infections were observed after f-K-Tx but fewer viral infections (27.0% vs 38.5%) as compared with re-K-Tx (P = .11). After f-K-Tx, urinary and gastrointestinal tract infections were more frequent; after re-K-Tx, respiratory tract and surgical site infections were more frequent (P < .001). Conclusions: ID events were less frequent after re-K-Tx. Affected sites differed significantly after f-K-Tx vs re-K-Tx.

Frequency and impact on renal transplant outcomes of urinary tract infections due to extended-spectrum beta-lactamase-producing Escherichia coli and Klebsiella species.

Background: Enterobacterales are often responsible for urinary tract infection (UTI) in kidney transplant recipients. Among these, Escherichia coli or Klebsiella species producing extended-spectrum beta-lactamase (ESBL) are emerging. However, there are only scarce data on frequency and impact of ESBL-UTI on transplant outcomes. Methods: We investigated frequency and impact of first-year UTI events with ESBL Escherichia coli and/or Klebsiella species in a prospective multicenter cohort consisting of 1,482 kidney transplants performed between 2012 and 2017, focusing only on 389 kidney transplants having at least one UTI with Escherichia coli and/or Klebsiella species. The cohort had a median follow-up of four years. Results: In total, 139/825 (17%) first-year UTI events in 69/389 (18%) transplant recipients were caused by ESBL-producing strains. Both UTI phenotypes and proportion among all UTI events over time were not different compared with UTI caused by non-ESBL-producing strains. However, hospitalizations in UTI with ESBL-producing strains were more often observed (39% versus 26%, p = 0.04). Transplant recipients with first-year UTI events with an ESBL-producing strain had more frequently recurrent UTI (33% versus 18%, p = 0.02) but there was no significant difference in one-year kidney function as well as longer-term graft and patient survival between patients with and without ESBL-UTI. Conclusion: First-year UTI events with ESBL-producing Escherichia coli and/or Klebsiella species are associated with a higher need for hospitalization but do neither impact allograft function nor allograft and patient survival.

Immune Monitoring-Guided Versus Fixed Duration of Antiviral Prophylaxis Against Cytomegalovirus in Solid-Organ Transplant Recipients: A Multicenter, Randomized Clinical Trial.

BACKGROUND: The use of assays detecting cytomegalovirus (CMV)-specific T cell-mediated immunity may individualize the duration of antiviral prophylaxis after transplantation. METHODS: In this randomized trial, kidney and liver transplant recipients from 6 centers in Switzerland were enrolled if they were CMV-seronegative with seropositive donors or CMV-seropositive receiving antithymocyte globulins. Patients were randomized to a duration of antiviral prophylaxis based on immune monitoring (intervention) or a fixed duration (control). Patients in the control group were planned to receive 180 days (CMV-seronegative) or 90 days (CMV-seropositive) of valganciclovir. Patients were assessed monthly with a CMV ELISpot assay (T-Track CMV); prophylaxis in the intervention group was stopped if the assay was positive. The co-primary outcomes were the proportion of patients with clinically significant CMV infection and reduction in days of prophylaxis. Between-group differences were adjusted for CMV serostatus. RESULTS: Overall, 193 patients were randomized (92 in the immune-monitoring group and 101 in the control group), of whom 185 had evaluation of the primary outcome (87 and 98 patients). CMV infection occurred in 26 of 87 (adjusted percentage, 30.9%) in the immune-monitoring group and in 32 of 98 (adjusted percentage, 31.1%) in the control group (adjusted risk difference, -0.1; 95% confidence interval [CI], -13.0% to 12.7%; P = .064). The duration of prophylaxis was shorter in the immune-monitoring group (adjusted difference, -26.0 days; 95%, CI, -41.1 to -10.8 days; P < .001). CONCLUSIONS: Immune monitoring resulted in a significant reduction of antiviral prophylaxis, but we were unable to establish noninferiority of this approach on the co-primary outcome of CMV infection. CLINICAL TRIALS REGISTRATION: NCT02538172.

Immunogenicity of High-Dose Versus MF59-Adjuvanted Versus Standard Influenza Vaccine in Solid Organ Transplant Recipients: The Swiss/Spanish Trial in Solid Organ Transplantation on Prevention of Influenza (STOP-FLU Trial).

BACKGROUND: The immunogenicity of the standard influenza vaccine is reduced in solid-organ transplant (SOT) recipients, so new vaccination strategies are needed in this population. METHODS: Adult SOT recipients from 9 transplant clinics in Switzerland and Spain were enrolled if they were >3 months after transplantation. Patients were randomized (1:1:1) to a MF59-adjuvanted or a high-dose vaccine (intervention), or a standard vaccine (control), with stratification by organ and time from transplant. The primary outcome was vaccine response rate, defined as a ≥4-fold increase of hemagglutination-inhibition titers to at least 1 vaccine strain at 28 days postvaccination. Secondary outcomes included polymerase chain reaction-confirmed influenza and vaccine reactogenicity. RESULTS: A total of 619 patients were randomized, 616 received the assigned vaccines, and 598 had serum available for analysis of the primary endpoint (standard, n = 198; MF59-adjuvanted, n = 205; high-dose, n = 195 patients). Vaccine response rates were 42% (84/198) in the standard vaccine group, 60% (122/205) in the MF59-adjuvanted vaccine group, and 66% (129/195) in the high-dose vaccine group (difference in intervention vaccines vs standard vaccine, 0.20; 97.5% confidence interval [CI], .12-1); P < .001; difference in high-dose vs standard vaccine, 0.24 [95% CI, .16-1]; P < .001; difference in MF59-adjuvanted vs standard vaccine, 0.17 [97.5% CI, .08-1]; P < .001). Influenza occurred in 6% of the standard, 5% in the MF59-adjuvanted, and 7% in the high-dose vaccine groups. Vaccine-related adverse events occurred more frequently in the intervention vaccine groups, but most of the events were mild. CONCLUSIONS: In SOT recipients, use of an MF59-adjuvanted or a high-dose influenza vaccine was safe and resulted in a higher vaccine response rate. CLINICAL TRIALS REGISTRATION: Clinicaltrials.gov NCT03699839.

Surgical site infections after kidney transplantation are independently associated with graft loss.

Surgical site infections (SSIs) are common health care-associated infections. SSIs after kidney transplantation (K-Tx) can endanger patient and allograft survival. Multicenter studies on this early posttransplant complication are scarce. We analyzed consecutive adult K-Tx recipients enrolled in the Swiss Transplant Cohort Study who received a K-Tx between May 2008 and September 2020. All data were prospectively collected with the exception of the categorization of SSI which was performed retrospectively according to the Centers for Disease Control and Prevention criteria. A total of 58 out of 3059 (1.9%) K-Tx recipients were affected by SSIs. Deep incisional (15, 25.9%) and organ/space infections (34, 58.6%) predominated. In the majority of SSIs (52, 89.6%), bacteria were detected, most frequently Escherichia coli (15, 28.9%), Enterococcus spp. (14, 26.9%), and coagulase-negative staphylococci (13, 25.0%). A BMI ≥25 kg/m2 (multivariable OR 2.16, 95% CI 1.07-4.34, P = .023) and delayed graft function (multivariable OR 2.88, 95% CI 1.56-5.34, P = .001) were independent risk factors for SSI. In Cox proportional hazard models, SSI was independently associated with graft loss (multivariable HR 3.75, 95% CI 1.35-10.38, P = .011). In conclusion, SSI was a rare complication after K-Tx. BMI ≥25 kg/m2 and delayed graft function were independent risk factors. SSIs were independently associated with graft loss.

[Frequency of Prescription of Non-steroidal Anti-inflammatory Drugs: Analysis of Compulsory Health Insurance Billing Data]. / Verschreibung von nicht-steroidalen Antirheumatika: Analyse von Abrechnungsdaten der OKP.

Frequency of Prescription of Non-steroidal Anti-inflammatory Drugs: Analysis of Compulsory Health Insurance Billing Data Abstract. According to the nephrology recommendation in the Choosing Wisely campaign, non-steroidal anti-inflammatory drugs should be avoided in people with cardiac and renal diseases. This study provides quantitative data on the use of NSAIDs in Switzerland as well as indications of how the billing frequency of NSAIDs in high-risk individuals has changed since the introduction of the recommendation. METHOD: Secondary analysis of billing data from compulsory health insurance. The frequency of NSAID use was stratified by sociodemographics and the comorbidities "cardiology" and "renal insufficiency". RESULTS: It was shown for the first time that 33.6% of the total study population, 42.1% of the cardiac risk population and 18% of the renal risk population used NSAIDs. There was a slight tendency for the billing frequency to decrease after the introduction of the recommendation. DISCUSSION: Further studies are needed as a matter of priority to quantify the use of potentially harmful NSAIDs in other risk groups and, on the basis of the ensuing study results, a wider use of the Choosing Wisely recommendations must be considered, especially in the general population.

Impact of different urinary tract infection phenotypes within the first year post-transplant on renal allograft outcomes.

In this study, we investigated the clinical impact of different urinary tract infection (UTI) phenotypes occurring within the first year after renal transplantation. The population included 2368 transplantations having 2363 UTI events. Patients were categorized into four groups based on their compiled UTI events observed within the first year after transplantation: (i) no colonization or UTI (n = 1404; 59%), (ii) colonization only (n = 353; 15%), (iii) occasional UTI with 1-2 episodes (n = 456; 19%), and (iv) recurrent UTI with ≥3 episodes (n = 155; 7%). One-year mortality and graft loss rate were not different among the four groups, but patients with recurrent UTI had a 7-10 ml/min lower eGFR at year one (44 ml/min vs. 54, 53, and 51 ml/min; p < .001). UTI phenotypes had no impact on long-term patient survival (p = .33). However, patients with recurrent UTI demonstrated a 10% lower long-term death-censored allograft survival (p < .001). Furthermore, recurrent UTI was a strong and independent risk factor for reduced death-censored allograft survival in a multivariable analysis (HR 4.41, 95% CI 2.53-7.68, p < .001). We conclude that colonization and occasional UTI have no impact on pertinent outcomes, but recurrent UTI are associated with lower one-year eGFR and lower long-term death-censored allograft survival. Better strategies to prevent and treat recurrent UTI are needed.

Impact of Hyponatremia after Renal Transplantation on Decline of Renal Function, Graft Loss and Patient Survival: A Prospective Cohort Study.

BACKGROUND: Hyponatremia is one of the most common electrolyte disorders observed in hospitalized and ambulatory patients. Hyponatremia is associated with increased falls, fractures, prolonged hospitalisation and mortality. The clinical importance of hyponatremia in the renal transplant field is not well established, so the aim of this study was to determine the relationships between hyponatremia and mortality as main outcome and renal function decline and graft loss as secondary outcome among a prospective cohort of renal transplant recipients. METHODS: This prospective cohort study included 1315 patients between 1 May 2008 and 31 December 2014. Hyponatremia was defined as sodium concentration below 136 mmol/L at 6 months after transplantation. The main endpoint was mortality. A secondary composite endpoint was also defined as: rapid decline in renal function (≥5 mL/min/1.73 m2 drop of the eGFR/year), graft loss or mortality. RESULTS: Mean sodium was 140 ± 3.08 mmol/L. 97 patients displayed hyponatremia with a mean of 132.9 ± 3.05 mmol/L. Hyponatremia at 6 months after transplantation was associated neither with mortality (HR: 1.02; p = 0.97, 95% CI: 0.47-2.19), nor with the composite outcome defined as rapid decline in renal function, graft loss or mortality (logrank test p = 0.9). CONCLUSIONS: Hyponatremia 6 months after transplantation is not associated with mortality in kidney allograft patients.

Pre-transplant donor-specific HLA antibodies and risk for poor first-year renal transplant outcomes: results from the Swiss Transplant Cohort Study.

The aim of this study was to analyze first year renal outcomes in a nationwide prospective multicenter cohort comprising 2215 renal transplants, with a special emphasis on the presence of pre-transplant donor-specific HLA antibodies (DSA). All transplants had a complete virtual crossmatch and DSA were detected in 19% (411/2215). The investigated composite endpoint was a poor first-year outcome defined as (i) allograft failure or (ii) death or (iii) poor allograft function (eGFR ≤25 ml/min/1.73 m2 ) at one year. Two hundred and twenty-one (221/2215; 10%) transplants showed a poor first-year outcome. Rejection (24/70; 34%) was the most common reason for graft failure. First-year patient's death was rare (48/2215; 2%). There were no statistically significant differences between DSA-positive and DSA-negative transplants regarding composite and each individual endpoint, as well as reasons for graft failure and death. DSA-positive transplants experienced more frequently rejection episodes, mainly antibody-mediated rejection (both P < 0.0001). The combination of DSA and any first year rejection was associated with the overall poorest death-censored allograft survival (P < 0.0001). In conclusion, presence of pre-transplant DSA per se does not affect first year outcomes. However, DSA-positive transplants experiencing first year rejection are a high-risk population for poor allograft survival and may benefit from intense clinical surveillance.

Age at Time of Kidney Transplantation as a Predictor for Mortality, Graft Loss and Self-Rated Health Status: Results From the Swiss Transplant Cohort Study.

Introduction: The effect of age on health outcomes in kidney transplantation remains inconclusive. This study aimed to analyze the relationship between age at time of kidney transplantation with mortality, graft loss and self-rated health status in adult kidney transplant recipients. Methods: This study used data from the Swiss Transplant Cohort Study and included prospective data of kidney transplant recipients between 2008 and 2017. Time-to-event analysis was performed using Cox' regression analysis, and -in the case of graft loss- competing risk analysis. A random-intercept regression model was applied to analyse self-rated health status. Results: We included 2,366 kidney transplant recipients. Age at transplantation linearly predicted mortality. It was also predictive for graft loss, though nonlinearly, showing that recipients aged between 35 and 55 years presented with the lowest risk of experiencing graft loss. No relationship of age with self-rated health status was detected. Conclusion: Higher mortality in older recipients complies with data from the general population. The non-linear relationship between age and graft loss and the higher scored self-rated health status at all follow-up time-points compared to the pre-transplant status -regardless of age- highlight that age alone might not be an accurate measure for risk prediction and clinical decision making in kidney transplantation.

[The renal transplant patient in primary care: do´s and don´ts]. / Der nierentransplantierte Patient in der Hausarztpraxis: dos and don'ts.

The renal transplant patient in primary care: do's and don'ts Abstract. Kidney transplantation is the best therapeutic option for patients with end-stage renal disease regarding mortality, quality of life and cost efficiency. In the medium to long term patients may be seen primarily by the general nephrologist and family physician. In this article we give a rough overview about care of the adult renal transplant recipient combined with practical advice for family doctors.

[Hyperkalemia - what the general practitioner must know]. / Hyperkaliämie - was der Hausarzt wissen muss.

Hyperkalemia can be a challenge for the general practitioner as it can prove to be benign as well as life-threatening. From a diagnostic point of view, four possibilities have to be differenciated: a pre-analytical cause, potassium release through cell lysis, a potassium shift, a reduced renal excretion of potassium. The first differential diagnosis can often be carried out by a thorough medical history, in particular the medication intake. Also, the first clinical and laboratory investigations can take place at the general practitioner's clinic. If the hyperkalemia proves to be a true hyperkalemia or cannot be explained by poly-medication and known diseases of the patient, not yet identified renal, endocrine or cardiac diseases should be searched for. If a serious condition is identified as the cause of hyperkalemia the patient should be referred to a specialized clinic.

Une hyperkaliémie peut représenter un challenge au cabinet médical car elle peut aussi bien s'avérer bénigne que menaçante pour la vie du patient. Sur le plan diagnostique, quatre possibilités sont à différencier: une cause pré-analytique, la libération de potassium par une lyse cellulaire, un déplacement du potassium, une diminution de l'excrétion rénale du potassium. Le premier diagnostic différentiel s'effectue souvent par une anamnèse précise, en particulier une anamnèse médicamenteuse. De même, les premières investigations cliniques et de laboratoire peuvent être faites au cabinet médical. Si l'hyperkaliémie ne s'avère pas être une pseudohyperkaliémie ou si une polymédication et la maladie de base ne suffisent pas à l'expliquer, une cause rénale, endocrinologique ou cardiaque ­ jusque-là méconnue ­ doit être recherchée. Si la cause de l'hyperkaliémie est une affection grave, le patient devrait être adressé à une consultation spécialisée.

Novel rescue procedure for inferior vena cava reconstruction in living-donor liver transplantation using a vascular graft recovered 25 h after donors' circulatory death and systematic review.

Liver transplantation is a lifesaving treatment for patients suffering from end-stage liver disease. Rarely, acute congestion of the inferior vena cava (IVC) is being encountered because of tumor compression. MELD allocation does not reflect severity of this condition because of lack of organ failure. Herein, a patient is being presented undergoing urgent living-donor liver transplantation (LDLT) with IVC reconstruction for a fast-growing hepatic epithelioid hemangioendothelioma (HEH). IVC reconstruction using a venous graft recovered from a 25-h after circulatory-death prior transplantation became necessary to compensate severe venous congestion. Additionally, a systematic review of the literature searching MEDLINE/PubMed was performed. Protocol and eligibility criteria were specified in advance and registered at the PROSPERO registry (CRD42013004827). Published literature of IVC reconstruction in LDLT was selected. Two reports describing IVC reconstruction with cryopreserved IVC grafts and one IVC reconstruction using a deceased after-circulatory-death-donor IVC graft were included. Follow-up was at 12 and 13 months, respectively. Regarding the graft recovery in the setting of living-related donation, this graft remained patent during the nine-month follow-up period. This is the first report on the use of a venous graft from a circulatory-death-donor, not eligible for whole organ recovery. We demonstrate in this study the feasibility of using a size and blood-group-compatible IVC graft from a cold-stored donor, which can solve the problem of urgent IVC reconstruction in patients undergoing LDLT.

Alterations of the thoracic spine in Marfan's syndrome.

OBJECTIVE: The purpose of this study was to determine if the thoracic vertebral elements are altered in patients with Marfan's syndrome. MATERIALS AND METHODS: Thirty patients underwent helical CT of the thorax because of suspected thoracic aortic dilatation and acute dissection. Thirteen had Marfan's syndrome and 17 did not. Two reviewers, unaware of the final diagnosis, evaluated the images by consensus for laminar thickness, foraminal width, dural sac ratios, and vertebral scalloping for T2-T12. RESULTS: At T9-T12, dural sac ratios at the midcorpus level (p = 0.031) and foraminal width (p = 0.0124) were significantly greater in the patients with Marfan's syndrome than in the patients without. Dural sac ratios at lower endplate levels (p = 0.0685), laminar thickness (p = 0.951), and vertebral scalloping (p = 0.24) were not significantly greater in the patients with Marfan's syndrome than in the patients without. CONCLUSION: Because the phenotypic expression of Marfan's syndrome is variable, information on the spine from thoracic studies in combination with major criteria may be helpful clinically.

Reoperations and late adverse outcome in Marfan patients following cardiovascular surgery.

OBJECTIVES: Anulo-aortic ectasia represents the most common cardiovascular manifestation requiring surgery in Marfan patients. Aim of this report was to analyze the type of presentation and the incidence of cardiovascular lesions and the clinical follow-up after initial surgery, mainly aortic root repair or replacement. METHODS: Between 1/1990 and 6/2003 a total of 71 patients (mean age 29+/-17 years, 8-65 years) received first surgical treatment at our institution. 69 received root repair or replacement. 22 patients presented with acute aortic dissection (31%), out of them, 3 pregnant females and 1 just after delivery. Composite graft replacement was performed in the majority of patients (61/71, 85%). Aortic valve sparing root repair was performed in 7 patients, supra-coronary graft with refixation of the aortic valve in 2 and replacement of the descending aorta in 1 patient. All patients underwent close clinical and imaging follow-up in a specialized outpatient consultation. RESULTS: During a mean follow-up interval of 5.2+/-1.8 years, 14 patients (20.5%) underwent a total of 27 aortic reoperations. Seven patients had one and 6 patients had up to 4 reoperations; 13/14 patients had chronic aortic dissection. There was no hospital mortality and no major cardiac or neurologic morbidity following reoperation. During follow-up, 2 patients suffered from acute type B dissection following aortic root surgery and 3 patients surprisingly died: 2 from a rupture of a normal-sized descending aorta and one from intracranial hemorrhage. These 5 patients had had uncomplicated primary aortic root operation. CONCLUSIONS: The incidence of reoperations is significantly higher in patients who presented initially with acute type A aortic dissection than in those with dilatation only. In addition, this survey demonstrates that unexpected fatal outcome may appear in the remaining native aorta following uncomplicated elective aortic root surgery, even if the aorta is normal-sized. A close follow-up of all Marfan patients is necessary to detect asymptomatic changes requiring surgery because complex elective redo-operations can be performed with a very low perioperative risk.