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Induction treatment with rabbit polyclonal antithymocyte globulins (ATGs) is frequent used in kidney transplant recipients with donorspecific HLA antibodies and shows acceptable outcomes. The two commonly used ATGs, Thymoglobulin and ATG-F have slightly different antigen profile and antibody concentrations. The two compounds have never been directly compared in a prospective trial in immunological high-risk recipients. Therefore we performed a prospective randomized controlled study comparing the two compounds in immunological high-risk kidney recipients in terms of safety and efficacy. Immunological high-risk kidney recipients, defined as the presence of HLA DSA but negative CDC-B and T-cell crossmatches were randomized 1:1 to receive ATG-F or Thymoglobulin. Maintenance immunosuppressive therapy consisted of tacrolimus, mycophenolate mofetil and steroids. The per-protocol analysis included 35 patients. There was no immediate infusion reaction observed with both compounds. No PTLD or malignancy occurred during the follow-up in both groups. The incidence of viral and bacterial infections was similar in both groups (p = 0.62). The cumulative incidence of clinical and subclinical antibody mediated allograft rejection as well as T-cell mediated allograft rejection during the first year between ATG-F and Thymoglobulin was similar (35% versus 19%; p = 0.30 and 11% versus 18%; 0.54 respectively). The two-year graft function was similar with a median eGFR of 56 ml/min/1.73m2 (range 21-128) (ATG-F-group) and 51 ml/min/1.73m2 (range 22-132) (Thymo-group) (p = 0.69). We found no significant differences between the compared study drugs for induction treatment in immunological high-risk patients regarding safety and efficacy during follow-up with good allograft function at 2 years after transplantation.

The human polyomaviruses BK virus and JC virus are nonenveloped viruses that have a diameter of 45 nm and a circular, double-stranded–DNA genome of 5300 bp. 1 Each of the two viruses is 70 percent homologous with the other and with simian virus 40 (SV40). 1 Typically, primary infection with the BK virus or JC virus occurs during childhood and does not produce specific symptoms; the prevalence on serologic testing is more than 80 percent among adults worldwide. 1 , 2 Serologic studies suggest that the BK virus and JC virus are transmitted independently of one another, most likely by the oral or respiratory . . .

Endothelins may play an important role in cyclosporine A (CsA)-induced renal vasoconstriction. Therefore, the effects of a mixed endothelin A and B receptor antagonist, bosentan (BO), on CsA were studied. BO was given either alone or combined with CsA to healthy subjects in a double-blind, placebo-controlled, cross-over study. Standardized renal hemodynamics took place after a single dose of BO or placebo and after seven days of regular intake of CsA + BO or CsA + placebo. CsA was administered as a dose-adjusted regimen to achieve predetermined target trough levels. A pharmacokinetic study of CsA and BO was performed. A single dose of BO did not affect renal hemodynamics. After seven days of coadministration with CsA, BO significantly attenuated both the overall CsA-induced fall of renal plasma flow (RPF; placebo, 594 ± 85; CsA + placebo, 490 ± 93; CsA + BO, 570 ± 106* mL/min, *P ß 0.01) and the maximal RPF fall (P ß 0.01) observed five hours after CsA intake. The CsA-induced rise of blood pressure and the decrease of glomerular filtration rate (GFR) were not influenced by comedication with BO. After seven days of CsA + BO, the area under the curve (AUC) of BO was nearly doubled compared with the AUC after a single dose of BO (P ß 0.05). To reach the CsA target trough levels after seven days, the average CsA dose was increased by 35% when given with BO, as compared with placebo (P = 0.01). CsA exposure (trough levels, AUC) was not statistically different after CsA + placebo and after CsA + BO. Assuming CsA nephrotoxicity is mainly due to vasoconstriction, BO has the potential to attenuate the CsA renal toxicity by markedly blunting the renal hypoperfusion effect of CsA. A complex drug interaction between BO and CsA was observed.

Background Urinary creatinine excretion is used as a marker of completeness of timed urine collections, which are a keystone of several metabolic evaluations in clinical investigations and epidemiological surveys. The current reference values for 24-hour urinary creatinine excretion rely on observations performed in the 1960s and 1970s in relatively small and mostly selected groups, and may thus poorly fit to the present-day general European population. The aim of this study was to establish and validate anthropometry-based age- and sex-specific reference values of the 24-hour urinary creatinine excretion on adult populations with preserved renal function. Methods We used data from two independent Swiss cross-sectional population-based studies with standardised 24-hour urinary collection and measured anthropometric variables. Only data from adults of European descent, with estimated glomerular filtration rate (eGFR) ≥60 ml/min/1.73 m 2 and reported completeness of the urinary collection were retained. A linear regression model was developed to predict centiles of the 24-hour urinary creatinine excretion in 1,137 participants from the Swiss Survey on Salt and validated in 994 participants from the Swiss Kidney Project on Genes in Hypertension. Results The mean urinary creatinine excretion was 193 ± 41 μmol/kg/24 hours in men and 151 ± 38 μmol/kg/24 hours in women in the Swiss Survey on Salt. The values were inversely correlated with age and body mass index (BMI). Based on current reference values (177 to 221 μmol/kg/24 hours in men and 133 to 177 μmol/kg/24 hours in women), 56% of the urinary collections in the whole population and 67% in people >60 years old would have been considered as inaccurate. A linear regression model with sex, BMI and age as predictor variables was found to provide the best prediction of the observed values and showed a good fit when applied to the validation population. Conclusions We propose a validated prediction equation for 24-hour urinary creatinine excretion in the general European population, based on readily available variables such as age, sex and BMI, and a few derived normograms to ease its clinical application. This should help healthcare providers to interpret the completeness of a 24-hour urine collection in daily clinical practice and in epidemiological population studies.

Background. Single-nudeotide polymorphisms (SNPs) in immune genes have been associated with susceptibility to invasive mold infection (IMI) among hematopoietic stem cell but not solid-organ transplant (SOT) recipients. Methods. Twenty-four SNPs from systematically selected genes were genotyped among 1101 SOT recipients (715 kidney transplant recipients, 190 liver transplant recipients, 102 lung transplant recipients, 79 heart transplant recipients, and 15 recipients of other transplants) from the Swiss Transplant Cohort Study. Association between SNPs and the end point were assessed by log-rank test and Cox regression models. Cytokine production upon Aspergillus stimulation was measured by enzyme-linked immunosorbent assay in peripheral blood mononuclear cells (PBMCs) from healthy volunteers and correlated with relevant genotypes. Results. Mold colonization (n = 45) and proven/probable IMI (n = 26) were associated with polymorphisms in the genes encoding interleukin Iß (IL1B; rs 16944; recessive mode, P = .001 for colonization and P = .00005 for IMI, by the log-rank test), interleukin 1 receptor antagonist (IL1RN; rs419598; P = .01 and P = .02, respectively), and β-defensin 1 (DEFB1; rs1800972; P= .001 and P = .0002, respectively). The associations with IL1B and DEFB1 remained significant in a multivariate regression model (P = .002 for IL1B rs16944; P = .01 for DEFB1 rs1800972). The presence of 2 copies of the rare allele of rs 16944 or rs419598 was associated with reduced Aspergillus-induced interleukin Iβ and tumor necrosis factor α secretion by PBMCs. Conclusions. Functional polymorphisms in IL IB and DEFB1 influence susceptibility to mold infection in SOT recipients. This observation may contribute to individual risk stratification.

Abstract 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. Lay Summary Patients living with a donor kidney need to take immunosuppressive medication to avoid organ rejection. As a result of the suppressed immune function, infections are a frequent complication. Kidney transplants do not often last the whole life of the patient, leading to a retransplantation. It is unknown whether the risk for infections is different after retransplantation. In this study, we analyzed 312 infections from 59 patients who underwent kidney retransplantation in the Swiss Transplant Cohort Study. Interestingly, we observed a lower infection rate after retransplantation. We found that bacterial infections were more frequent after the first transplantation, viral infections were more frequent after retransplantation, and there were differences in infection sites. Our results highlight that the risk for infections is different after a retransplantation. Hence, prophylactic strategies to avoid posttransplant infections might be adapted for patients undergoing retransplantation. Graphical Abstract Graphical abstract This graphical abstract is also available at Tidbit: https://tidbitapp.io/tidbits/do-infectious-diseases-after-kidney-re-transplantation-differ-from-those-after-first-kidney-transplantation/update

Metabolic syndrome after transplantation is a major concern following solid organ transplantation (SOT). The CREB-regulated transcription co-activator 2 (CRTC2) regulates glucose metabolism. The effect of CRTC2 polymorphisms on new-onset diabetes after transplantation (NODAT) was investigated in a discovery sample of SOT recipients ( n 1 =197). Positive results were tested for replication in two samples from the Swiss Transplant Cohort Study (STCS, n 2 =1294 and n 3 =759). Obesity and other metabolic traits were also tested. Associations with metabolic traits in population-based samples ( n 4 =46’186, n 5 =123’865, n 6 >100,000) were finally analyzed. In the discovery sample, CRTC2 rs8450 - AA genotype was associated with NODAT, fasting blood glucose and body mass index ( P corrected <0.05). CRTC2 rs8450 - AA genotype was associated with NODAT in the second STCS replication sample (odd ratio (OR)=2.01, P =0.04). In the combined STCS replication samples, the effect of rs8450 - AA genotype on NODAT was observed in patients having received SOT from a deceased donor and treated with tacrolimus ( n =395, OR=2.08, P =0.02) and in non-kidney transplant recipients (OR=2.09, P =0.02). Moreover, rs8450 - AA genotype was associated with overweight or obesity ( n =1215, OR=1.56, P =0.02), new-onset hyperlipidemia ( n =1007, OR=1.76, P =0.007), and lower high-density lipoprotein-cholesterol ( n =1214, β=-0.08, P =0.001). In the population-based samples, a proxy of rs8450G>A was significantly associated with several metabolic abnormalities. CRTC2 rs8450G>A appears to have an important role in the high prevalence of metabolic traits observed in patients with SOT. A weak association with metabolic traits was also observed in the population-based samples.

Rhodococcus equi is an animal pathogen that sometimes causes opportunistic infections in immunocompromised patients. Speck et al . present the case of a 62-year-old male renal transplant recipient who presented with fever, hemoptysis and left-sided pleuritic chest pain. After numerous investigations, a diagnosis of R. equi infection with bacteremic pleuropneumonia and pseudotumor was made. This Case Study describes the diagnosis and management of R. equi infection, which has a very varied clinical presentation in humans. Background A 62-year-old male kidney transplant recipient was admitted to hospital with a 14-day history of fever, hemoptysis and left-sided pleuritic chest pain. He had suffered malaise, weight loss, night sweats and exertional dyspnea over the previous 3 months. Imaging studies of the patient's chest revealed a noncavitated mass measuring 5 × 8 cm in the anterior segment of the left upper lobe of the lung and a left-sided pleural effusion with septa, and bacterial cultures revealed the presence of Rhodococcus equi . Investigations Physical examination, laboratory tests, chest X-ray, CT scan of the chest, bronchoscopy, and bacterial culture of blood, sputum, bronchoalveolar lavage fluid and pleural fluid. Diagnosis R. equi infection with bacteremic pleuropneumonia and pseudotumor. A secondary myopathy occurred 6 months after diagnosis of the infection as a result of a drug interaction between clarithromycin and simvastatin. Management Long-term combination antibiotic therapy (ciprofloxacin plus vancomycin or clarithromycin), resection of the inflammatory pseudotumor, and reduction of immunosuppressive therapy. Following the diagnosis of myopathy, simvastatin was discontinued.

Hypocalcaemia often occurs in patients after parathyroidectomy (PTX) due to hypoparathyroidism and/or hungry bone syndrome. To avoid hypocalcaemia, patients are substituted with large doses of calcium and vitamin D. Here, we present four patients, who developed acute renal failure with hypercalcaemia and/or histologically confirmed nephrocalcinosis after PTX due to oversubstitution with vitamin D analogues and calcium. As a consequence, serum and urinary calcium should be closely monitored after PTX, and calcium and vitamin D substitution should be continuously adapted to avoid not only hypocalcaemia but also nephrocalcinosis and hypercalcaemic renal failure.