Clinical practice guideline for the management of lipids in adults with diabetic kidney disease: abbreviated summary of the Joint Association of British Clinical Diabetologists and UK Kidney Association (ABCD-UKKA) Guideline 2024.

The contribution of chronic kidney disease (CKD) towards the risk of developing cardiovascular disease (CVD) is magnified with co-existing type 1 or type 2 diabetes. Lipids are a modifiable risk factor and good lipid management offers improved outcomes for people with diabetic kidney disease (DKD).The primary purpose of this guideline, written by the Association of British Clinical Diabetologists (ABCD) and UK Kidney Association (UKKA) working group, is to provide practical recommendations on lipid management for members of the multidisciplinary team involved in the care of adults with DKD.

Central and peripheral myeloid-derived suppressor cell-like cells are closely related to the clinical severity of multiple sclerosis.

Multiple sclerosis (MS) is a highly heterogeneous demyelinating disease of the central nervous system (CNS) that needs for reliable biomarkers to foresee disease severity. Recently, myeloid-derived suppressor cells (MDSCs) have emerged as an immune cell population with an important role in MS. The monocytic-MDSCs (M-MDSCs) share the phenotype with Ly-6Chi-cells in the MS animal model, experimental autoimmune encephalomyelitis (EAE), and have been retrospectively related to the severity of the clinical course in the EAE. However, no data are available about the presence of M-MDSCs in the CNS of MS patients or its relation with the future disease aggressiveness. In this work, we show for the first time cells exhibiting all the bona-fide phenotypical markers of M-MDSCs associated with MS lesions, whose abundance in these areas appears to be directly correlated with longer disease duration in primary progressive MS patients. Moreover, we show that blood immunosuppressive Ly-6Chi-cells are strongly related to the future severity of EAE disease course. We found that a higher abundance of Ly-6Chi-cells at the onset of the EAE clinical course is associated with a milder disease course and less tissue damage. In parallel, we determined that the abundance of M-MDSCs in blood samples from untreated MS patients at their first relapse is inversely correlated with the Expanded Disability Status Scale (EDSS) at baseline and after a 1-year follow-up. In summary, our data point to M-MDSC load as a factor to be considered for future studies focused on the prediction of disease severity in EAE and MS.

Clinical practice guidelines for management of hyperglycaemia in adults with diabetic kidney disease.

A significant percentage of people with diabetes develop chronic kidney disease and diabetes is also a leading cause of end-stage kidney disease (ESKD). The term diabetic kidney disease (DKD) includes both diabetic nephropathy (DN) and diabetes mellitus and chronic kidney disease (DM CKD). DKD is associated with high morbidity and mortality, which are predominantly related to cardiovascular disease. Hyperglycaemia is a modifiable risk factor for cardiovascular complications and progression of DKD. Recent clinical trials of people with DKD have demonstrated improvement in clinical outcomes with sodium glucose co-transporter-2 (SGLT-2) inhibitors. SGLT-2 inhibitors have significantly reduced progression of DKD and onset of ESKD and these reno-protective effects are independent of glucose lowering. At the time of this update Canagliflozin and Dapagliflozin have been approved for delaying the progression of DKD. The Association of British Clinical Diabetologists (ABCD) and UK Kidney Association (UKKA) Diabetic Kidney Disease Clinical Speciality Group have undertaken a literature review and critical appraisal of the available evidence to inform clinical practice guidelines for management of hyperglycaemia in adults with DKD. This 2021 guidance is for the variety of clinicians who treat people with DKD, including GPs and specialists in diabetes, cardiology and nephrology.

Association of British Clinical Diabetologists and Renal Association guidelines on the detection and management of diabetes post solid organ transplantation.

Post-transplant diabetes mellitus (PTDM) is common after solid organ transplantation (SOT) and associated with increased morbidity and mortality for allograft recipients. Despite the significant burden of disease, there is a paucity of literature with regards to detection, prevention and management. Evidence from the general population with diabetes may not be translatable to the unique context of SOT. In light of emerging clinical evidence and novel anti-diabetic agents, there is an urgent need for updated guidance and recommendations in this high-risk cohort. The Association of British Clinical Diabetologists (ABCD) and Renal Association (RA) Diabetic Kidney Disease Clinical Speciality Group has undertaken a systematic review and critical appraisal of the available evidence. Areas of focus are; (1) epidemiology, (2) pathogenesis, (3) detection, (4) management, (5) modification of immunosuppression, (6) prevention, and (7) PTDM in the non-renal setting. Evidence-graded recommendations are provided for the detection, management and prevention of PTDM, with suggested areas for future research and potential audit standards. The guidelines are endorsed by Diabetes UK, the British Transplantation Society and the Royal College of Physicians of London. The full guidelines are available freely online for the diabetes, renal and transplantation community using the link below. The aim of this review article is to introduce an abridged version of this new clinical guideline ( https://abcd.care/sites/abcd.care/files/site_uploads/Resources/Position-Papers/ABCD-RA%20PTDM%20v14.pdf).

[Clinical and epidemiological characteristics of SARS-CoV-2 infections in family physicians: A case-control study]. / Características clínico-epidemiológicas de la infección por el virus SARS-CoV-2 en médicos de familia: un estudio de casos y controles.

OBJECTIVE: To identify the sociodemographic, clinical and epidemiological characteristics associated with the presence of infection by the SARS-CoV-2 virus in family physicians who carry out their work in Primary Care (PC) or in Hospital Emergencies. DESING: Observational analytical case-control study. SITE: Primary care. PARTICIPANTS: 969 Primare Care Physicians, Hospital Emergency physicians and other extrahospitalry centers that had PCR for the detection of the SARS-CoV-2. Of these, 133 participated as cases (PCR positive) and 836 as controls (PCR negative). INTERVENTIONS: No. MAIN MEASUREMENTS: Sociodemographic and work, contact with a COVID-19 patient, symptoms present during the process, first manifested symptom, previous chronic pathologies, and tobacco use. RESULTS: 13.7% (95% CI: 11.6-16.0) were cases infected with SARS-CoV-2. The most frequently declared symptoms by those infected were a feeling of fatigue/tiredness (69.2%; 95% CI: 60.9-77.4%), cough (56.4%; 95% CI: 47.6-65.2%) and headache (55.6%; 95% CI: 46.8-64.4%).Using logistic regression, the variables independently associated with SARS-CoV-2 virus infection in Family Physicians were: previous contact with a COVID-19 patient (OR: 2.3; 95% CI: 1.2-4.2), present fatigue / tiredness (OR: 2.2; 95% CI: 1.2-3.9), smell alteration (4.6; 95% CI: 1.7-12.5), taste alteration (OR: 32.0; 95% CI: 9.6-106.8), cough (OR: 3.0; 95% CI: 1.7-5.3) and fever (OR: 6.1; 95% CI: 3.2-11.4). CONCLUSIONS: Symptoms independently related to SARS-CoV-2 virus infection in Family Physicians were fatigue, fever, cough, and altered taste and smell. The presence of these symptoms could facilitate the diagnosis of suspected COVID-19 disease and the earlier selection of those that require confirmatory tests.

[Hereditary breast and ovarian cancer syndrome: Diagnosis and therapeutic implications]. / Syndrome héréditaire de prédisposition au cancer du sein et de l'ovaire : diagnostic et implications thérapeutiques.

Patients who carry the BReast Cancer 1 or 2 (BRCA) gene mutations have an underlying hereditary predisposition for breast and ovarian cancers. These deleterious genetic mutations are the most common ones implicated in hereditary breast and ovarian cancers. Oncogenetic counselling plays a key role in identifying patient for BRCA testing and for mutation identification. BRCA1/2 carriers have to be followed up regularly and may justify breast and/or adnexal prophylactic surgery, according to the French National Cancer Institute guidelines (INCa). Poly- (DNA-riboses) polymerases inhibitors, notably olaparib, have a major role in the management of epithelial ovarian cancer in patients with BRCA mutation and many studies are ongoing to expand their indications in a near future.

Clinical-pathological correlations in post-transplant thrombotic microangiopathy.

AIMS: Post-transplant thrombotic microangiopathy (TMA) is a rare and clinically challenging finding in renal transplant biopsies. In addition to recurrent atypical haemolytic uraemic syndrome, TMA in renal transplants is associated with various conditions, such as calcineurin inhibitor (CNI) treatment, antibody-mediated rejection (ABMR), viral infections, sepsis, pregnancy, malignancies, and surgery. The therapeutic implications of this diagnosis are considerable. In order to better understand post-transplant TMA and to identify histological or clinical differences between associated causes, we conducted a multicentre retrospective study. METHODS AND RESULTS: Clinical parameters and transplant renal biopsy findings from 81 patients with TMA were analysed. Biopsies from 38 patients were also analysed with electron microscopy. On the basis of clinical-pathological correlation, TMA was attributed to a main aetiology, whenever possible. TMA occurred at a median of 30 days post-transplantation. Systemic features of TMA were present in only 18% of cases. Twenty-two per cent of cases were attributed to CNI and 11% to ABMR. Although other potentially contributing factors were found in 56% of patients, in most cases (63%) no clearly attributable cause of TMA was identified. Histological differences between groups were minimal. The detection of ultrastructural features that are usually associated with ABMR may help to establish ABMR as the cause of TMA. CONCLUSIONS: Although CNI and ABMR appear to be the main contributors to post-transplant TMA, the aetiology of most cases is probably multifactorial, and TMA cannot be unequivocally attributed to a single underlying aetiology. Morphological features of TMA are not discriminating, but electron microscopy may help to identify ABMR-associated TMA.

Guillain-Barré syndrome following the 2009 pandemic monovalent and seasonal trivalent influenza vaccination campaigns in Spain from 2009 to 2011: outcomes from active surveillance by a neurologist network, and records from a country-wide hospital discharge database.

BACKGROUND: Studies have shown a slight excess risk in Guillain-Barré syndrome (GBS) incidence associated with A(H1N1)pdm09 vaccination campaign and seasonal trivalent influenza vaccine immunisations in 2009-2010. We aimed to assess the incidence of GBS as a potential adverse effect of A(H1N1)pdm09 vaccination. METHODS: A neurologist-led network, active at the neurology departments of ten general hospitals serving an adult population of 4.68 million, conducted GBS surveillance in Spain in 2009-2011. The network, established in 1996, carried out a retrospective and a prospective study to estimate monthly alarm thresholds in GBS incidence and tested them in 1998-1999 in a pilot study. Such incidence thresholds additionally to observation of GBS cases with immunisation antecedent in the 42 days prior to clinical onset were taken as alarm signals for 2009-2011, since November 2009 onwards. For purpose of surveillance, in 2009 we updated both the available centres and the populations served by the network. We also did a retrospective countrywide review of hospital-discharged patients having ICD-9-CM code 357.0 (acute infective polyneuritis) as their principal diagnosis from January 2009 to December 2011. RESULTS: Among 141 confirmed of 148 notified cases of GBS or Miller-Fisher syndrome, Brighton 1-2 criteria in 96 %, not a single patient was identified with clinical onset during the 42-day time interval following A(H1N1)pdm09 vaccination. In contrast, seven cases were seen during a similar period after seasonal campaigns. Monthly incidence figures did not, however, exceed the upper 95 % CI limit of expected incidence. A retrospective countrywide review of the registry of hospital-discharged patients having ICD-9-CM code 357.0 (acute infective polyneuritis) as their principal diagnosis did not suggest higher admission rates in critical months across the period December 2009-February 2010. CONCLUSIONS: Despite limited power and underlying reporting bias in 2010-2011, an increase in GBS incidence over background GBS, associated with A(H1N1)pdm09 monovalent or trivalent influenza immunisations, appears unlikely.

CCL18 synergises with high concentrations of glucose in stimulating fibronectin production in human renal tubuloepithelial cells.

BACKGROUND: Diabetic nephropathy is the leading cause of end stage kidney disease worldwide. The pathogenesis of this disease remains elusive and multiple factors have been implicated. These include the effects of hyperglycaemia, haemodynamic and metabolic factors, and an inflammatory process that stimulates cellular signalling pathways leading to disease progression and severe fibrosis. Fibronectin (Fn) is an important protein of the extracellular matrix that is essential in fibrosis and its presence in increased amounts has been identified in the kidney in diabetic nephropathy. METHODS: Proximal tubuloepithelial (HK-2) cells were stimulated with high glucose (30 mM D-glucose) or glycated albumin (500 µg/mmol) + 4 mM D-glucose or their controls, Mannitol (26 mM + 4 mM D-glucose) and 4 mM D-glucose, respectively. Following 48 h of stimulation the supernatant was collected and MTT [3-(4,5-dimethylthiazole-2,5-diphenyltetrazolium bromide] assay performed to assess cell viability. HK-2 cells were also stimulated in the above environments with recombinant CCL18 (rCCL18) or MCP-1 (rMCP-1) for 48 h with quantification of Fn levels using ELISA. RESULTS: Co-stimulation of HK-2 cells with high concentrations of glucose and rCCL18 significantly increased Fn (p < 0.001), in comparison to high concentrations of glucose alone. HK-2 cells stimulated with glycated albumin consistently produced Fn and this did not alter following co-stimulation with rCCL18 or rMCP-1. CONCLUSION: This study demonstrates how stimulation with a specific chemokine CCL18 in high glucose upregulates the production of Fn from proximal tubuloepithelial cells. This may be relevant to the development of renal fibrosis in diabetic nephropathy.

Machine Learning-Based Time in Patterns for Blood Glucose Fluctuation Pattern Recognition in Type 1 Diabetes Management: Development and Validation Study.

BACKGROUND: Continuous glucose monitoring (CGM) for diabetes combines noninvasive glucose biosensors, continuous monitoring, cloud computing, and analytics to connect and simulate a hospital setting in a person's home. CGM systems inspired analytics methods to measure glycemic variability (GV), but existing GV analytics methods disregard glucose trends and patterns; hence, they fail to capture entire temporal patterns and do not provide granular insights about glucose fluctuations. OBJECTIVE: This study aimed to propose a machine learning-based framework for blood glucose fluctuation pattern recognition, which enables a more comprehensive representation of GV profiles that could present detailed fluctuation information, be easily understood by clinicians, and provide insights about patient groups based on time in blood fluctuation patterns. METHODS: Overall, 1.5 million measurements from 126 patients in the United Kingdom with type 1 diabetes mellitus (T1DM) were collected, and prevalent blood fluctuation patterns were extracted using dynamic time warping. The patterns were further validated in 225 patients in the United States with T1DM. Hierarchical clustering was then applied on time in patterns to form 4 clusters of patients. Patient groups were compared using statistical analysis. RESULTS: In total, 6 patterns depicting distinctive glucose levels and trends were identified and validated, based on which 4 GV profiles of patients with T1DM were found. They were significantly different in terms of glycemic statuses such as diabetes duration (P=.04), glycated hemoglobin level (P<.001), and time in range (P<.001) and thus had different management needs. CONCLUSIONS: The proposed method can analytically extract existing blood fluctuation patterns from CGM data. Thus, time in patterns can capture a rich view of patients' GV profile. Its conceptual resemblance with time in range, along with rich blood fluctuation details, makes it more scalable, accessible, and informative to clinicians.

Management of Hypertension in Patients With Diabetic Kidney Disease: Summary of the Joint Association of British Clinical Diabetologists and UK Kidney Association (ABCD-UKKA) Guideline 2021.

Diabetic kidney disease (DKD) accounts for >40% cases of chronic kidney disease (CKD) globally. Hypertension is a major risk factor for progression of DKD and the high incidence of cardiovascular disease and mortality in these people. Meticulous management of hypertension is therefore crucial to slow down the progression of DKD and reduce cardiovascular risk. Randomized controlled trial evidence differs in type 1 and type 2 diabetes and in different stages of DKD in terms of target blood pressure (BP). Renin-angiotensin blocking agents reduce progression of DKD and cardiovascular events in both type 1 and type 2 diabetes, albeit differently according to the stage of CKD. There is emerging evidence for the benefit of sodium glucose cotransporter 2, nonsteroidal selective mineralocorticoid antagonists, and endothelin-A receptor antagonists in slowing progression and reducing cardiovascular events in DKD. This UK guideline, developed jointly by diabetologists and nephrologists, has reviewed all available current evidence regarding the management of hypertension in DKD to produce a set of comprehensive individualized recommendations for BP control and the use of antihypertensive agents according to age, type of diabetes, and stage of CKD (https://ukkidney.org/sites/renal.org/files/Management-of-hypertension-and-RAAS-blockade-in-adults-with-DKD.pdf). A succinct summary of the guideline, including an infographic, is presented here.

Incidence, Risk Factors, and Effect on Allograft Survival of Glomerulonephritis Post-transplantation in a United Kingdom Population: Cohort Study.

Background: Post-transplant glomerulonephritis (PTGN) has been associated with inferior long-term allograft survival, and its incidence varies widely in the literature. Methods: This is a cohort study of 7,623 patients transplanted between 2005 and 2016 at four major transplant UK centres. The diagnosis of glomerulonephritis (GN) in the allograft was extracted from histology reports aided by the use of text-mining software. The incidence of the four most common GN post-transplantation was calculated, and the risk factors for disease and allograft outcomes were analyzed. Results: In total, 214 patients (2.8%) presented with PTGN. IgA nephropathy (IgAN), focal segmental glomerulosclerosis (FSGS), membranous nephropathy (MN), and membranoproliferative/mesangiocapillary GN (MPGN/MCGN) were the four most common forms of post-transplant GN. Living donation, HLA DR match, mixed race, and other ethnic minority groups were associated with an increased risk of developing a PTGN. Patients with PTGN showed a similar allograft survival to those without in the first 8 years of post-transplantation, but the results suggest that they do less well after that timepoint. IgAN was associated with the best allograft survival and FSGS with the worst allograft survival. Conclusions: PTGN has an important impact on long-term allograft survival. Significant challenges can be encountered when attempting to analyze large-scale data involving unstructured or complex data points, and the use of computational analysis can assist.

Frequency and predictive validity of olfactory and taste dysfunction in patients with SARS-CoV-2 infection.

BACKGROUND AND OBJECTIVE: Olfactory and taste dysfunction (OD, TD) have been considered symptoms of SARS-CoV-2 infection. However, its presence in certain populations, especially those with mild clinical symptoms, has not been clarified. The objective was to estimate the frequency of OD and TD, and its predictive validity in patients detected in Primary Care. PATIENTS AND METHODS: A cross-sectional study was carried out in the Spanish National Health System. An epidemiological survey was administered to patients who were requested the PCR test for SARS-CoV-2. Odds ratio (OR) were estimated to measure the magnitude of the association between OD and TD and the existence of SARS-CoV-2 infection. The sensitivity, specificity, and positive and negative predictive values (PPV, NPV) of these symptoms in SARS-CoV-2 infection were calculated. RESULTS: Of 1038 patients screened, 20.1% had SARS-CoV-2 infection. OD and DG were present in 64.4% (95% CI 56.0-72.1) and 56.2% (95% CI 47.9-64.2) of the subjects with infection, respectively. The OR for OD was 12.2 (95% CI 8.26-18.06) and for TD was 7.95 (95% CI 5.48-11.53). TD presented a sensitivity of 41.1% (95% CI 34.4-46.1), a specificity of 91.9% (95% CI 89.8-93.7), a PPV of 56.2% (95% CI48.0-64.2) and a NPV of 86.1% (95% CI 83.6-88.3), while the OD showed a sensitivity of 45.0% (95% CI 37.6-51.5), a specificity of 93.7% (95% CI 91.8-95.0), a PPV of 64.4% (95% CI 56.0-72.1) and a NPV of 87.1% (95% CI 84.7-89.2). CONCLUSIONS: More than half of the subjects with SARS-CoV-2 infection have OD or TD. The presence of OD or TD could be of diagnostic utility due to its ability to predict infection in more than half of the cases.

ANTECEDENTES Y OBJETIVO: La disfunción olfatoria (DO) y gustativa (DG) han demostrado ser síntomas de la infección por SARS-CoV-2. Sin embargo, su presencia en determinadas poblaciones, sobre todo en aquellas con cuadros clínicos leves, aún debe aclararse. El objetivo fue estimar la frecuencia de DO y DG, y su validez predictiva en pacientes detectados en Atención Primaria. PACIENTES Y MÉTODOS: Se realizó un estudio transversal en el Sistema Nacional de Salud español. Se administró una encuesta epidemiológica dirigida a pacientes a los que se les solicitó la prueba PCR para SARS-CoV-2. Se estimaron las odds ratio (OR) para medir la magnitud de la asociación entre la DO y DG y la existencia de infección por SARS-CoV-2. Se calculó la sensibilidad, la especificidad y los valores predictivos positivos (VPP) y negativos (VPN) de estos síntomas en la infección por SARS-CoV-2. RESULTADOS: Se captaron 1.038 pacientes, de los cuales el 20,1% presentaban infección por SARS-CoV-2. Las DO y DG estuvieron presentes en el 64,4% (IC 95% 56,0­72,1) y el 56,2% (IC 95% 47,9­64,2) de los sujetos con infección, respectivamente. La OR para la DO fue de 12,2 (IC 95% 8,26−18,06) y para la DG de 7,95 (IC 95% 5,48−11.53). La DG presentó una sensibilidad del 41,1% (IC 95% 34,4­46,1), una especificidad del 91,9% (IC 95% 89,8­93,7), un VPP del 56,2% (IC 95% 48,0­64,2) y un VPN de 86,1% (IC 95% 83,6­88,3), mientras que la DO mostró una sensibilidad del 45,0% (IC 95% 37,6­51,5), una especificidad del 93,7% (IC 95% 91,8­95,0), un VPP del 64,4% (IC 95% 56,0­72,1) y un VPN del 87,1% (IC 95% 84,7­89,2). CONCLUSIONES: Más de la mitad de los sujetos con infección por SARS-CoV-2 presentan DO o DG. La presencia de DO o de DG podría ser de utilidad diagnostica por su capacidad para predecir la infección en más de la mitad de las ocasiones.

[Frequency and predictive validity of olfactory and taste dysfunction in patients with SARS-CoV-2 infection]. / Frecuencia de aparición y validez predictiva de la disfunción olfatoria y del gusto en pacientes con infección por SARS-CoV-2.

BACKGROUND AND OBJECTIVE: Olfactory and taste dysfunction (OD, TD) have been considered symptoms of SARS-CoV-2 infection. However, its presence in certain populations, especially those with mild clinical symptoms, has not been clarified. The objective was to estimate the frequency of OD and TD, and its predictive validity in patients detected in Primary Care. PATIENTS AND METHODS: A cross-sectional study was carried out in the Spanish National Health System. An epidemiological survey was administered to patients who were requested the PCR test for SARS-CoV-2. Odds ratio (OR) were estimated to measure the magnitude of the association between OD and TD and the existence of SARS-CoV-2 infection. The sensitivity, specificity, and positive and negative predictive values (PPV, NPV) of these symptoms in SARS-CoV-2 infection were calculated. RESULTS: Of 1,038 patients screened, 20.1% had SARS-CoV-2 infection. OD and DG were present in 64.4% (95% CI 56.0-72.1) and 56.2% (95% CI 47.9-64.2) of the subjects with infection, respectively. The OR for OD was 12.2 (95% CI 8.26-18.06) and for TD was 7.95 (95% CI 5.48-11.53). TD presented a sensitivity of 41.1% (95% CI 34.4-46.1), a specificity of 91.9% (95% CI 89.8-93.7), a PPV of 56.2% (95% CI48.0-64.2) and a NPV of 86.1% (95% CI 83.6-88.3), while the OD showed a sensitivity of 45.0% (95% CI 37.6-51.5), a specificity of 93.7% (95% CI 91.8-95.0), a PPV of 64.4% (95% CI 56.0-72.1) and a NPV of 87.1% (95% CI 84.7-89.2). CONCLUSIONS: More than half of the subjects with SARS-CoV-2 infection have OD or TD. The presence of OD or TD could be of diagnostic utility due to its ability to predict infection in more than half of the cases.

Development of a multivariable gene-expression signature targeting T-cell-mediated rejection in peripheral blood of kidney transplant recipients validated in cross-sectional and longitudinal samples.

BACKGROUND: Acute T-cell mediated rejection (TCMR) is usually indicated by alteration in serum-creatinine measurements when considerable transplant damage has already occurred. There is, therefore, a need for non-invasive early detection of immune signals that would precede the onset of rejection, prior to transplant damage. METHODS: We examined the RT-qPCR expression of 22 literature-based genes in peripheral blood samples from 248 patients in the Kidney Allograft Immune Biomarkers of Rejection Episodes (KALIBRE) study. To account for post-transplantation changes unrelated to rejection, we generated time-adjusted gene-expression residuals from linear mixed-effects models in stable patients. To select genes, we used penalised logistic regression based on 27 stable patients and 27 rejectors with biopsy-proven T-cell-mediated rejection, fulfilling strict inclusion/exclusion criteria. We validated this signature in i) an independent group of stable patients and patients with concomitant T-cell and antibody-mediated-rejection, ii) patients from an independent study, iii) cross-sectional pre-biopsy samples from non-rejectors and iv) longitudinal follow-up samples covering the first post-transplant year from rejectors, non-rejectors and stable patients. FINDINGS: A parsimonious TCMR-signature (IFNG, IP-10, ITGA4, MARCH8, RORc, SEMA7A, WDR40A) showed cross-validated area-under-ROC curve 0.84 (0.77-0.88) (median, 2.5th-97.5th centile of fifty cross-validation cycles), sensitivity 0.67 (0.59-0.74) and specificity 0.85 (0.75-0.89). The estimated probability of TCMR increased seven weeks prior to the diagnostic biopsy and decreased after treatment. Gene expression in all patients showed pronounced variability, with up to 24% of the longitudinal samples in stable patients being TCMR-signature positive. In patients with borderline changes, up to 40% of pre-biopsy samples were TCMR-signature positive. INTERPRETATION: Molecular marker alterations in blood emerge well ahead of the time of clinically overt TCMR. Monitoring a TCMR-signature in peripheral blood could unravel T-cell-related pro-inflammatory activity and hidden immunological processes. This additional information could support clinical management decisions in cases of patients with stable but poor kidney function or with inconclusive biopsy results.

Defining Phenotypes in Diabetic Nephropathy: a novel approach using a cross-sectional analysis of a single centre cohort.

The global increase in Diabetes Mellitus (DM) has led to an increase in DM-Chronic Kidney Disease (DM-CKD). In this cross-sectional observational study we aimed to define phenotypes for patients with DM-CKD that in future may be used to individualise treatment We report 4 DM-CKD phenotypes in 220 patients recruited from Imperial College NHS Trust clinics from 2004-2012. A robust principal component analysis (PCA) was used to statistically determine clusters with phenotypically different patients. 163 patients with complete data sets were analysed: 77 with CKD and 86 with DM-CKD. Four different clusters were identified. Phenotypes 1 and 2 are entirely composed of patients with DM-CKD and phenotypes 3 and 4 are predominantly CKD (non-DM-CKD). Phenotype 1 depicts a cardiovascular phenotype; phenotype 2: microvascular complications with advanced DM-CKD; phenotype 3: advanced CKD with less anaemia, lower weight and HbA1c; phenotype 4: hypercholesteraemic, younger, less severe CKD. We are the first group to describe different phenotypes in DM-CKD using a PCA approach. Identification of phenotypic groups illustrates the differences and similarities that occur under the umbrella term of DM-CKD providing an opportunity to study phenotypes within these groups thereby facilitating development of precision/personalised targeted medicine.

Características clínico-epidemiológicas de la infección por el virus SARS-CoV-2 en médicos de familia: un estudio de casos y controles / Clinical and epidemiological characteristics of SARS-CoV-2 infections in family physicians: A case-control study

Objetivo: Identificar las características sociodemográficas, clínicas y epidemiológicas asociadas a la presencia de infección por el virus SARS-CoV-2 en médicos de familia que desempeñan su actividad laboral en atención primaria (AP) o en urgencias de hospital. Diseño: Estudio observacional analítico de casos y controles. Emplazamiento: Atención primaria. Participantes: Un total de 969 médicos de AP, urgencias hospitalarias y otros centros extrahospitalarios que dispusieran de RT-PCR para la detección del virus SARS-CoV-2. De estos, 133 participaron como casos (PCR positiva) y 836 como controles (PCR negativa).Intervenciones: No. Mediciones principales: Variables sociodemográficas y laborales, contacto con enfermo de COVID-19, síntomas presentes durante el proceso, primer síntoma manifestado, enfermedades crónicas previas y consumo de tabaco. Resultados: Del total de la muestra el 13,7% (IC 95%: 11,6-16,0), eran casos infectados con el SARS-CoV-2. Los síntomas declarados más frecuentemente por los infectados fueron sensación de fatiga/cansancio (69,2%; IC 95%: 60,9-77,4%), tos (56,4%; IC 95%: 47,6-65,2%) y cefalea (55,6%; IC 95%: 46,8-64,4%). Mediante regresión logística, las variables asociadas de manera independiente con la infección por virus SARS-CoV-2 en médicos de familia fueron: contacto previo con enfermo COVID-19 (OR: 2,3; IC 95%: 1,2-4,2), presentar fatiga/cansancio (OR: 2,2; IC 95%: 1,2-3,9), alteración del olfato (4,6; IC 95%: 1,7-12,5), alteración del gusto (OR: 32,0; IC 95%: 9,6-106,8), tos (OR: 3,0; IC 95%: 1,7-5,3) y fiebre (OR: 6,1; IC 95%: 3,2-11,4). Conclusiones: Los síntomas relacionados de forma independiente con la infección por el virus SARS-CoV-2 en médicos de familia fueron la fatiga, la fiebre, la tos y la alteración del gusto y del olfato. La presencia de estos síntomas podría facilitar el diagnóstico de sospecha de enfermedad COVID-19 y la selección más precoz de aquellos que precisan pruebas de confirmación.(AU)

Objective: To identify the sociodemographic, clinical and epidemiological characteristics associated with the presence of infection by the SARS-CoV-2 virus in family physicians who carry out their work in Primary Care (PC) or in Hospital Emergencies. Desing: Observational analytical case-control study. Site: Primary care. Participants: 969 Primare Care Physicians, Hospital Emergency physicians and other extrahospitalry centers that had PCR for the detection of the SARS-CoV-2. Of these, 133 participated as cases (PCR positive) and 836 as controls (PCR negative). Interventions: No. Main measurements: Sociodemographic and work, contact with a COVID-19 patient, symptoms present during the process, first manifested symptom, previous chronic pathologies, and tobacco use. Results: 13.7% (95% CI: 11.6-16.0) were cases infected with SARS-CoV-2. The most frequently declared symptoms by those infected were a feeling of fatigue/tiredness (69.2%; 95% CI: 60.9-77.4%), cough (56.4%; 95% CI: 47.6-65.2%) and headache (55.6%; 95% CI: 46.8-64.4%).Using logistic regression, the variables independently associated with SARS-CoV-2 virus infection in Family Physicians were: previous contact with a COVID-19 patient (OR: 2.3; 95% CI: 1.2-4.2), present fatigue / tiredness (OR: 2.2; 95% CI: 1.2-3.9), smell alteration (4.6; 95% CI: 1.7-12.5), taste alteration (OR: 32.0; 95% CI: 9.6-106.8), cough (OR: 3.0; 95% CI: 1.7-5.3) and fever (OR: 6.1; 95% CI: 3.2-11.4). Conclusions: Symptoms independently related to SARS-CoV-2 virus infection in Family Physicians were fatigue, fever, cough, and altered taste and smell. The presence of these symptoms could facilitate the diagnosis of suspected COVID-19 disease and the earlier selection of those that require confirmatory tests.(AU)

Frecuencia de aparición y validez predictiva de la disfunción olfatoria y del gusto en pacientes con infección por SARS-CoV-2 / Frequency and predictive validity of olfactory and taste dysfunction in patients with SARS-CoV-2 infection

Antecedentes y objetivo: La disfunción olfatoria (DO) y gustativa (DG) han demostrado ser síntomas de la infección por SARS-CoV-2. Sin embargo, su presencia en determinadas poblaciones, sobre todo en aquellas con cuadros clínicos leves, aún debe aclararse. El objetivo fue estimar la frecuencia de DO y DG, y su validez predictiva en pacientes detectados en Atención Primaria.Pacientes y métodosSe realizó un estudio transversal en el Sistema Nacional de Salud español. Se administró una encuesta epidemiológica dirigida a pacientes a los que se les solicitó la prueba PCR para SARS-CoV-2. Se estimaron las odds ratio (OR) para medir la magnitud de la asociación entre la DO y DG y la existencia de infección por SARS-CoV-2. Se calculó la sensibilidad, la especificidad y los valores predictivos positivos (VPP) y negativos (VPN) de estos síntomas en la infección por SARS-CoV-2.ResultadosSe captaron 1.038 pacientes, de los cuales el 20,1% presentaban infección por SARS-CoV-2. Las DO y DG estuvieron presentes en el 64,4% (IC 95% 56,0-72,1) y el 56,2% (IC 95% 47,9-64,2) de los sujetos con infección, respectivamente. La OR para la DO fue de 12,2 (IC 95% 8,26-18,06) y para la DG de 7,95 (IC 95% 5,48-11.53). La DG presentó una sensibilidad del 41,1% (IC 95% 34,4-46,1), una especificidad del 91,9% (IC 95% 89,8-93,7), un VPP del 56,2% (IC 95% 48,0-64,2) y un VPN de 86,1% (IC 95% 83,6-88,3), mientras que la DO mostró una sensibilidad del 45,0% (IC 95% 37,6-51,5), una especificidad del 93,7% (IC 95% 91,8-95,0), un VPP del 64,4% (IC 95% 56,0-72,1) y un VPN del 87,1% (IC 95% 84,7-89,2).ConclusionesMás de la mitad de los sujetos con infección por SARS-CoV-2 presentan DO o DG. La presencia de DO o de DG podría ser de utilidad diagnostica por su capacidad para predecir la infección en más de la mitad de las ocasiones. (AU)

Background and objective: Olfactory and taste dysfunction (OD, TD) have been considered symptoms of SARS-CoV-2 infection. However, its presence in certain populations, especially those with mild clinical symptoms, has not been clarified. The objective was to estimate the frequency of OD and TD, and its predictive validity in patients detected in Primary Care.Patients and methodsA cross-sectional study was carried out in the Spanish National Health System. An epidemiological survey was administered to patients who were requested the PCR test for SARS-CoV-2. Odds ratio (OR) were estimated to measure the magnitude of the association between OD and TD and the existence of SARS-CoV-2 infection. The sensitivity, specificity, and positive and negative predictive values (PPV, NPV) of these symptoms in SARS-CoV-2 infection were calculated.ResultsOf 1,038 patients screened, 20.1% had SARS-CoV-2 infection. OD and DG were present in 64.4% (95% CI 56.0-72.1) and 56.2% (95% CI 47.9-64.2) of the subjects with infection, respectively. The OR for OD was 12.2 (95% CI 8.26-18.06) and for TD was 7.95 (95% CI 5.48-11.53). TD presented a sensitivity of 41.1% (95% CI 34.4-46.1), a specificity of 91.9% (95% CI 89.8-93.7), a PPV of 56.2% (95% CI48.0-64.2) and a NPV of 86.1% (95% CI 83.6-88.3), while the OD showed a sensitivity of 45.0% (95% CI 37.6-51.5), a specificity of 93.7% (95% CI 91.8-95.0), a PPV of 64.4% (95% CI 56.0-72.1) and a NPV of 87.1% (95% CI 84.7-89.2).ConclusionsMore than half of the subjects with SARS-CoV-2 infection have OD or TD. The presence of OD or TD could be of diagnostic utility due to its ability to predict infection in more than half of the cases. (AU)

Staged Hand-Assisted Bilateral Native Nephrectomy for Management of Posttransplant Polyuria in an Adult with Dent's Disease.

Polyuria after kidney transplantation causes graft dysfunction and increased thrombotic risk. We present a case of a polyuric adult with Dent's disease who underwent staged bilateral native nephrectomies, the first operation before transplant and the second four months after transplant. This led to improved allograft function maintained during four years of follow-up. The retroperitoneal laparoscopic approach was well tolerated and allowed continuation of peritoneal dialysis before transplantation. A staged approach helps regulate fluid balance perioperatively and may be tailored to individual need according to posttransplant urine output. This novel approach should be considered for polyuric patients with tubular dysfunction including Dent's disease.