Urinary calprotectin as a diagnostic tool for detecting significant bacteriuria.

Pyuria in dipstick examination serves as the most widespread screening tool for urinary tract infections (UTI). The absence of pyuria, however, does not exclude UTI. We investigated the diagnostic value of urinary calprotectin, a mediator protein of the innate immune system, which is released by leukocytes, for the detection of UTI and compared it with dipstick pyuria. Since even low numbers of leukocytes in the urine significantly increase urinary calprotectin concentrations, calprotectin might be a more sensitive marker than pyuria detected by dipstick. All 162 patients were prospectively included and underwent a urine dipstick, urine culture, quantification of proteinuria and determination of calprotectin in the urine. Urinary calprotectin was determined using an enzyme-linked immunosorbent assay (ELISA). UTI was defined as urine cultures with detection of one or a maximum of two uropathogenic bacteria with ≥ 105 colony-forming units per millilitre (CFU/ml). Exclusion criteria were acute kidney injury, chronic renal insufficiency and tumors of the urinary tract. 71 (43.8%) patients had a UTI. Of the 91 patients without UTI, 23 had a contamination and 19 had evidence of ≥ 105 CFU/ml considered to be asymptomatic bacteriuria. The median calprotectin concentration in patients with UTI and pyuria was significantly higher than in patients with UTI and without pyuria (5510.4 vs. 544.7 ng/ml). In ROC analyses, calprotectin revealed an area under the curve (AUC) of 0.70 for the detection of significant bacteriuria. Pyuria in dipstick examinations provided an AUC of 0.71. There was no significant difference between these AUCs in the DeLong test (p = 0.9). In patients with evidence of significant bacteriuria but without pyuria, a significantly higher calprotectin concentration was measured in the urine than in patients with neither pyuria nor UTI (544.7 ng/ml vs 95.6 ng/ml, p = 0.029). Urinary calprotectin is non-inferior to dipstick pyuria in the detection of UTI.

Dysfunctional high-density lipoprotein in chronic inflammatory rheumatic diseases.

Background: The mechanism explaining low cholesterol concentrations in chronic inflammatory rheumatic disease (CIRD) is incompletely understood. We hypothesized that chronic inflammation impairs the functionality of high-density lipoprotein (HDL), for example, by oxidative processes. Objectives: Assessment of oxidized HDL (HDLox), a marker of dysfunctional HDL, in newly diagnosed patients with CIRD before and after initiation of immunosuppressive therapy and comparison of HDLox values of patients with CIRD to non-CIRD controls. Design: Prospective observational trial. Methods: The study was conducted on 44 newly diagnosed CIRD patients, who were initiated on immunosuppressive therapy (baseline). A total of 136 patients without CIRD served as control. Lipid profiles including HDLox levels and C-reactive protein (CRP) were measured in both groups at baseline. In CIRD patients, measurements were repeated 12 weeks after baseline. Validated outcome tools for disease activity and function were assessed at baseline and 12 weeks. Results: A total of 33 (75%) patients with rheumatoid arthritis, 7(16%) with axial spondyloarthritis, and 4 (9%) with systemic lupus erythematosus were included. Groups were comparable for age and BMI. CIRD patients had higher HDLox concentrations (1.57 versus 0.78, p = 0.02) and tended to have lower low-density lipoprotein cholesterol, HDL cholesterol, and cholesterol concentrations compared to controls. HDLox (1.57 versus 1.4, p = 0.26) and CRP levels (2.1 versus 0.7 mg/dl, p < 0.01) decreased in CIRD patients from baseline to follow-up. Conclusion: CIRD is associated with an impairment of the anti-inflammatory properties of HDL as reflected by an increase in HDLox concentrations. This effect may contribute to the increased cardiovascular risk in chronic inflammatory diseases.

Patient knowledge about biosimilars and satisfaction with the education provided by rheumatologists or nurse specialists in a biosimilar multiswitch scenario - The perception study.

OBJECTIVE: To study the knowledge of patients with chronic inflammatory rheumatic diseases (CIRD) about biosimilars (bsDMARDs), assess patients' satisfaction after being educated about switching of bsDMARDs by rheumatologists compared to nurse specialists, and to explore the impact of multiple switches on patient satisfaction. METHODS: Adult patients with CIRD who underwent a non-medical switch from the adalimumab bsDMARDs GP2017 to the adalimumab bsDMARDs MSB 11022 were 1:1 randomized with randomly selected block sizes into two groups in which information about multiple switching of bsDMARDs was provided by either a nurse specialist or a rheumatologist. Validated outcome tools and standardized parameters for disease activity and function were assessed at baseline and 12 weeks after the switch. The primary endpoint was to evaluate whether satisfaction with care differs when education about switching is provided by rheumatologists or nurse specialists. Secondary endpoints were patients' knowledge about bsDMARDs and the efficacy and safety of switching in routine care. Patients' satisfaction with care was assessed by the Leeds Satisfaction Questionnaire. A structured questionnaire was used to assess the patient's knowledge. RESULTS: A total of 102 patients was randomized, with 40 educated by rheumatologists (39.2%) and 62 by nurse specialists (60.8%). Patients had moderate to low disease activity and limited impairment of physical function without progression on follow-up, implying that switching did not affected disease activity. Almost half of the patients (n = 50, 49%) had undergone one and 52 multiple switches (51%), respectively. Less than one-third of patients were able to correctly answer questions on manufacturing, effectiveness, clinical trial evidence, and cost of bsDMARDs. Patients were generally satisfied with the education - irrespective of whether the information had been provided by nurses or rheumatologists. No relevant differences in the outcomes assessed were observed. Efficacy and safety results were consistent with previously published data. CONCLUSION: Patient satisfaction after education about bsDMARDs and multiple switching by nurses and rheumatologists was equally good. Multiple switches had no negative impact on patient satisfaction, and outcomes after switching of bsDMARDs did not significantly worsen. Patients' knowledge about bsDMARDS was limited.

Biopsy findings after detection of de novo donor-specific antibodies in renal transplant recipients: a single center experience.

BACKGROUND: De novo donor-specific antibodies (DSA) are associated with an increased risk of antibody-mediated rejection and a substantial reduction of allograft survival. We hypothesized that detection of DSA should prompt a biopsy even in the absence of proteinuria and loss of estimated glomerular filtration rate (eGFR). However, data on a population without proteinuria or loss of kidney function is scant, and this is the main novelty of our study design. METHODS: Single center retrospective analysis on biopsy findings after detection of de novo DSA. One-hundred-thirty-two kidney and pancreas-kidney transplant recipients were included. Eighty-four of these patients (63.6%) underwent allograft biopsy. At the time of biopsy n = 50 (59.5%) had a protein/creatinine ratio (PCR) > 300 mg/g creatinine and/or a loss of eGFR ≥ 10 ml/min in the previous 12 months, whereas 40.5% did not. Diagnosis of rejection was performed according to Banff criteria. RESULTS: Seventy-seven (91.7%) of the biopsies had signs of rejection (47.6% antibody mediated rejection (ABMR), 13.1% cellular, 20.2% combined, 10.7% borderline). Among subjects without proteinuria or loss of eGFR ≥ 10 ml/min/a (n = 34), 29 patients (85.3%) showed signs of rejection (44.1% antibody mediated (ABMR), 14.7% cellular, 11.8% combined, 14.7% borderline). CONCLUSION: The majority of subjects with de novo DSA have histological signs of rejection, even in the absence of proteinuria and deterioration of graft function. Thus, it appears reasonable to routinely perform an allograft biopsy after the detection of de novo DSA.

Psychological Responses to the Coronavirus Disease 2019 Pandemic in Renal Transplant Recipients.

BACKGROUND: Renal transplant recipients are at increased risk for an adverse course of coronavirus disease 2019 (COVID-19), most likely due to immunosuppression and the high level of cardiovascular comorbidity. Many transplant recipients are aware of these facts. The psychological effects of this knowledge, however, remain elusive. METHODS: Cross-sectional study on 62 renal transplant recipients. Fifty cardiovascular outpatients without immunosuppression and 55 healthy subjects served as control. We performed a focused psychological assessment during the pandemic (April 2020) and compared the data with a time 6 months before. Additionally, an intergroup analysis was performed for the data during the pandemic. The analysis was performed by means of a questionnaire derived from KPD-38. We extracted 5 questions focusing on the parameters "life satisfaction" and perceived "action competence." Life satisfaction score ranged from 2 to 8, and the score for action competence from 5 to 20. RESULTS: Both life satisfaction and perceived action competence were significantly lower during the pandemic than 6 months before in all the 3 groups (P < .005 each). During the pandemic median levels of life satisfaction did not significantly differ between the 3 groups (transplant recipients 6, interquartile range [IQR] 4-7; cardiovascular patients 5, IQR: 4-6; healthy controls 6, IQR 5-7; Kruskal-Wallis P > .05). In contrast, the perceived action competence was higher in healthy subjects (15, IQR 12-17) than in both renal transplant recipients (13, IQR 10-15) and cardiovascular patients (13, IQR 8-14, Kruskal-Wallis P = .0003). CONCLUSION: The COVID-19 pandemic has negative effects on life satisfaction and perceived action competence in renal transplant recipients, cardiovascular patients without immunosuppression, and healthy subjects. The effects on life satisfaction in transplant recipients did not differ from nonimmunocompromised patients or healthy controls. In contrast, the feeling of reduced action competence exceeded healthy controls, most likely due to a subjective need for stricter social distancing to avoid infection.

Vaccination Against Urinary Tract Infection After Renal Transplantation.

BACKGROUND: Recurrent urinary tract infections (UTIs) increase mortality and reduce graft survival after renal transplantation. Because current prophylactic strategies such as methionine, cranberry juice, and antibiotics fail to sufficiently prevent recurrent infections in a substantial number of patients, there is a clinical need for alternative approaches. The present work describes first experiences with an immunization strategy against bacterial strains after kidney transplantation. METHODS: We performed a retrospective single-center analysis of an immunization approach against 10 strains of inactivated bacteria (StroVac). A total of 14 renal transplant recipients with 3 or more UTI episodes/year underwent immunization with 3 subcutaneous injections of inactivated bacteria (follow-up 12 months before to 12 months after immunization). These patients were compared to 14 renal transplant patients without immunization who were matched for number of UTIs and time after transplantation (24 months follow-up). We compared the UTI incidence and potential side effects, including development of de novo donor-specific antibodies (DSA). RESULTS: The immunization significantly decreased the incidence of UTIs from 3.4 ± 1.3 to 0.9 ± 1.0 by 74.9%. The incidence did not change from year 1 to year 2 of the observation period in the control group. Immunization was tolerated well, without any clinical complaints. There were no de novo DSAs in the first year after immunization. CONCLUSIONS: Immunization against inactivated bacterial strains substantially reduced the incidence of UTIs without eliciting any safety concerns in this small cohort of renal transplant recipients. This strategy may be a helpful expansion of our preventive measures in patients with recurrent UTIs.