Randomized clinical trial of non-antibiotic prophylaxis with d-Mannose plus Proanthocyanidins vs. Proanthocyanidins alone for urinary tract infections and asymptomatic bacteriuria in de novo kidney transplant recipients: The Manotras study.

BACKGROUND: Studies analyzing non-antibiotic alternatives in kidney transplant UTI's are lacking. d-Mannose, a simple sugar, inhibits bacterial attachment to the urothelium, as does Proanthocyanidins; both could act as a synergic strategy preventing UTI; nonetheless their efficacy and safety have not been evaluated in kidney transplant population yet. METHODS: This is a pilot prospective, double-blind randomized trial. Sixty de novo kidney transplant recipients were randomized (1:1) to receive a prophylactic strategy based on a 24-h prolonged release formulation of d-Mannose plus Proanthocyanidins vs. Proanthocyanidins (PAC) alone. The supplements were taken for the first 3 months after kidney transplant and then followed up for 3 months as well. The main objective of the study was to search if the addition of Mannose to PAC alone reduced the incidence of UTI and/or asymptomatic bacteriuria in the first 6 months post-transplantation. RESULTS: 27% of patients experienced one UTI episode (cystitis or pyelonephritis) while asymptomatic bacteriuria was very common (57%). Incidences according UTI type or AB were: 7% vs. 4% for cystitis episode (p 0.3), 4% vs. 5% for pyelonephritis (p 0.5) and 17% vs. 14% for asymptomatic bacteriuria (p 0.4) for patients in the Mannose+PAC group vs. PAC group respectively. The most frequent bacteria isolated in both groups was Escherichia coli (28% of all episodes), UTI or AB due to E. coli was not different according to study group (30% vs. 23% for Mannose+PAC vs. PAC alone p 0.37). CONCLUSIONS: Non-antibiotic therapy is an unmet need to prevent UTI after kidney transplantation; however, the use of d-Mannose plus PAC does not seem capable to prevent it.

False positive elevation in serum creatinine: a case report.

Background: Paraproteins can interfere with several substances, producing erroneous laboratory measurements. The diagnosis of kidney disease in patients with hematological disorders has important prognosis implications. An elevated creatinine with no other signs of kidney disease should prompt the idea of a spurious creatinine. Communication between the clinical team and the laboratory is key. Case presentation: In this case, we present a 68-year-old woman with an elevated creatinine and an IgM lambda paraprotein. Interestingly, there were no other signs of chronic kidney disease besides the creatinine value, with no albuminuria or microhematuria. A kidney biopsy showed normal parenchyma and ruled out the possibility of paraprotein-related damage. The monoclonal component and creatinine levels raised parallelly during follow-up while maintaining normal urea levels. This prompted the hypothesis of a falsely elevated creatinine. It was confirmed with a normal glomerular filtration rate determined by a radioisotope, a cystatin C measurement and a reduction in creatinine when diluting the sample. Conclusion: It is important to consider the possibility of a falsely elevated creatinine in patients with paraproteinemia and no other signs of kidney disease to avoid unnecessary diagnostic tests and for the prognostic implications.

The coexistence of diabetic retinopathy and diabetic nephropathy is associated with worse kidney outcomes.

Background: Up to 50-60% of patients with diabetes have non-diabetic kidney disease (NDKD) on kidney biopsy. Diabetic retinopathy (DR) is a microvascular complication of diabetes frequently associated with diabetic nephropathy (DN). The objective of the current study was to investigate the kidney outcomes and survival in patients with biopsy diagnoses of DN and NDKD according to the presence of DR. Methods: We conducted an observational, multicentre and retrospective study of the pathological findings of renal biopsies from 832 consecutive patients with diabetes from 2002 to 2014 from 18 nephrology departments. The association of DR with kidney replacement therapy (KRT) or survival was assessed by Kaplan-Meier and Cox regression analyses. Results: Of 832 patients with diabetes and renal biopsy, 768 had a retinal examination and 221/768 (22.6%) had DR. During a follow-up of 10 years, 288/760 (37.9%) patients with follow-up data needed KRT and 157/760 (20.7%) died. The incidence of KRT was higher among patients with DN (alone or with NDKD) and DR [103/175 (58.9%)] than among patients without DR [88/216 (40.7%), P < .0001]. The incidence of KRT was also higher among patients with only NDKD and DR than among those without DR [18/46 (39.1%) versus 79/331 (23.9%), P < .0001]. In multivariate analysis, DR or DN were independent risk factors for KRT {hazard ratio [HR] 2.48 [confidence interval (CI) 1.85-3.31], P < .001}. DN (with or without DR) was also identified as an independent risk factor for mortality [HR 1.81 (CI 1.26-2.62), P = .001]. Conclusions: DR is associated with a higher risk of progression to kidney failure in patients with histological DN and in patients with NDKD.

High exposure to tacrolimus is associated with spontaneous remission of recurrent membranous nephropathy after kidney transplantation.

Introduction: We aimed to characterize the incidence and clinical presentation of membranous nephropathy (MN) after kidney transplantation (KT), and to assess allograft outcomes according to proteinuria rates and immunosuppression management. Methods: Multicenter retrospective cohort study including patients from six Spanish centers who received a KT between 1991-2019. Demographic, clinical, and histological data were collected from recipients with biopsy-proven MN as primary kidney disease (n = 71) or MN diagnosed de novo after KT (n = 4). Results: Up to 25.4% of patients with biopsy-proven MN as primary kidney disease recurred after a median time of 18.1 months posttransplant, without a clear impact on graft survival. Proteinuria at 3-months post-KT was a predictor for MN recurrence (rMN, HR 4.28; P = 0.008). Patients who lost their grafts had higher proteinuria during follow-up [1.0 (0.5-2.5) vs 0.3 (0.1-0.5) g/24 h], but only eGFR after recurrence treatment predicted poorer graft survival (eGFR < 30 ml/min: RR = 6.8). We did not observe an association between maintenance immunosuppression and recurrence diagnosis. Spontaneous remission after rMN was associated with a higher exposure to tacrolimus before recurrence (trough concentration/dose ratio: 2.86 vs 1.18; P = 0.028). Up to 94.4% of KT recipients received one or several treatments after recurrence onset: 22.2% rituximab, 38.9% increased corticosteroid dose, and 66.7% ACEi/ARBs. Only 21 patients had proper antiPLA2R immunological monitoring. Conclusions: One-fourth of patients with biopsy-proven MN as primary kidney disease recurred after KT, without a clear impact on graft survival. Spontaneous remission after rMN was associated with a higher exposure to tacrolimus before recurrence.

Late poor outcomes of Clostridioides difficile infections in oncological patients: A multicentre cohort study.

Background: Cancer has been associated with an increased risk of in-hospital mortality in CDI patients. However, data on delayed mortality in cancer patients with CDI are scarce. Aim/Objective: The aim of the present study was to compare outcomes between oncological patients and the general population with Clostridioides difficile infection (CDI) after 90 days of follow-up. Methods: A multicenter prospective cohort study was conducted in 28 hospitals participating in the VINCat program. Cases were all consecutive adult patients who met the case definition of CDI. Sociodemographic, clinical, and epidemiological variables and evolution at discharge and after 90 days were recorded for each case. Findings/results: The mortality rate was higher in oncological patients (OR = 1.70, 95% CI: 1.08-2.67). In addition, oncological patients receiving chemotherapy (CT) presented higher recurrence rates (18.5% vs 9.8%, p = 0.049). Among oncological patients treated with metronidazole, those with active CT showed a higher rate of recurrence (35.3% vs 8.0% p = 0.04). Discussion: Oncological patients presented a higher risk of poor outcomes after CDI. Their early and late mortality rates were higher than in the general population, and in parallel, those undergoing chemotherapy (especially those receiving metronidazole) had higher rates of recurrence.

Persistent COVID-19 symptoms 1 year after hospital discharge: A prospective multicenter study.

OBJECTIVE: To determine the health status and exercise capacity of COVID-19 survivors one year after hospital discharge. METHODS: This multicenter prospective study included COVID-19 survivors 12 months after hospital discharge. Participants were randomly selected from a large cohort of COVID-19 patients who had been hospitalized until 15th April 2020. They were interviewed about persistent symptoms, underwent a physical examination, chest X-ray, and a 6-minute walk test (6MWT). A multivariate analysis was performed to determine the risk factors for persistent dyspnea. RESULTS: Of the 150 patients included, 58% were male and the median age was 63 (IQR 54-72) years. About 82% reported ≥1 symptoms and 45% had not recovered their physical health. The multivariate regression analysis revealed that the female sex, chronic obstructive pulmonary disease, and smoking were independent risk factors for persistent dyspnea. Approximately 50% completed less than 80% of the theoretical distance on the 6MWT. Only 14% had an abnormal X-ray, showing mainly interstitial infiltrates. A third of them had been followed up in outpatient clinics and 6% had undergone physical rehabilitation. CONCLUSION: Despite the high rate of survivors of the first wave of the COVID-19 pandemic with persistent symptomatology at 12 months, the follow-up and rehabilitation of these patients has been really poor. Studies focusing on the role of smoking in the persistence of COVID-19 symptoms are lacking.

Adoption of a novel smart mobile-health application technology to track chronic immunosuppression adherence in solid organ transplantation: Results of a prospective, observational, multicentre, pilot study.

BACKGROUND: Low adherence to chronic immunosuppression is associated with suboptimal transplantation outcomes. Mobile-health technology is a promising tool to monitor medication adherence, but data on patient engagement to these tools are lacking. METHODS: Prospective, observational, multicenter, 2-phase trial in kidney and liver transplant recipients, investigating the degree of engagement to TrackYourMed® (TYM), a novel m-Health technology with a QR code-scan app to track immunosuppression adherence and its association with drug monitoring. RESULTS: Out of 204 consecutive transplant patients, 90 patients were eligible to participate. 61 (68%) used TYM regularly, 21 (23%) never or barely used it, 5 (5.5%) were irregular users, and 3 (3.3%) were lost to follow-up. 6-month total correct intakes (CIN) ranged between 69%-76%, 12%-19% intakes were out-of-time (OUT), and 9%-12% were missed (MIS). Notably, a rate of intakes out of the scheduled time higher than 20% in the 6 days prior to blood immunosuppressant trough levels was associated with a higher intra-patient variability (17 IQR 13-21% vs. 29 IQR 23%-36%, p = .001), and with a higher dose-adjustment (p < .001). At 1 year, 53(59%) patients were still active users of TYM. CONCLUSIONS: Implementing m-Health technologies promoting immunosuppression adherence may be useful for a relevant number of transplant patients and help transplant physicians identifying erratic immunosuppression adherence.

Risk factors for non-diabetic renal disease in diabetic patients.

BACKGROUND: Diabetic patients with kidney disease have a high prevalence of non-diabetic renal disease (NDRD). Renal and patient survival regarding the diagnosis of diabetic nephropathy (DN) or NDRD have not been widely studied. The aim of our study is to evaluate the prevalence of NDRD in patients with diabetes and to determine the capacity of clinical and analytical data in the prediction of NDRD. In addition, we will study renal and patient prognosis according to the renal biopsy findings in patients with diabetes. METHODS: Retrospective multicentre observational study of renal biopsies performed in patients with diabetes from 2002 to 2014. RESULTS: In total, 832 patients were included: 621 men (74.6%), mean age of 61.7 ± 12.8 years, creatinine was 2.8 ± 2.2 mg/dL and proteinuria 2.7 (interquartile range: 1.2-5.4) g/24 h. About 39.5% (n = 329) of patients had DN, 49.6% (n = 413) NDRD and 10.8% (n = 90) mixed forms. The most frequent NDRD was nephroangiosclerosis (NAS) (n = 87, 9.3%). In the multivariate logistic regression analysis, older age [odds ratio (OR) = 1.03, 95% CI: 1.02-1.05, P < 0.001], microhaematuria (OR = 1.51, 95% CI: 1.03-2.21, P = 0.033) and absence of diabetic retinopathy (DR) (OR = 0.28, 95% CI: 0.19-0.42, P < 0.001) were independently associated with NDRD. Kaplan-Meier analysis showed that patients with DN or mixed forms presented worse renal prognosis than NDRD (P < 0.001) and higher mortality (P = 0.029). In multivariate Cox analyses, older age (P < 0.001), higher serum creatinine (P < 0.001), higher proteinuria (P < 0.001), DR (P = 0.007) and DN (P < 0.001) were independent risk factors for renal replacement therapy. In addition, older age (P < 0.001), peripheral vascular disease (P = 0.002), higher creatinine (P = 0.01) and DN (P = 0.015) were independent risk factors for mortality. CONCLUSIONS: The most frequent cause of NDRD is NAS. Elderly patients with microhaematuria and the absence of DR are the ones at risk for NDRD. Patients with DN presented worse renal prognosis and higher mortality than those with NDRD. These results suggest that in some patients with diabetes, kidney biopsy may be useful for an accurate renal diagnosis and subsequently treatment and prognosis.