NITRATE-CIN Study: Protocol of a Randomized (1:1) Single-Center, UK, Double-Blind Placebo-Controlled Trial Testing the Effect of Inorganic Nitrate on Contrast-Induced Nephropathy in Patients Undergoing Coronary Angiography for Acute Coronary Syndromes

Background: Contrast-induced nephropathy (CIN), an acute kidney injury resulting from the administration of intravascular iodinated contrast media, is a significant cause of morbidity/mortality following coronary angiographic procedures in high-risk patients. Despite preventative measures intended to mitigate the risk of CIN, there remains a need for novel effective treatments. Evidence suggests that delivery of nitric oxide (NO) through chemical reduction of inorganic nitrate to NO may offer a novel therapeutic strategy to reduce CIN and thus preserve long term renal function. Design: The NITRATE-CIN trial is a single-center, randomized, double-blind placebo-controlled trial, which plans to recruit 640 patients presenting with acute coronary syndromes (ACS) who are at risk of CIN. Patients will be randomized to either inorganic nitrate therapy (capsules containing 12 mmol KNO3) or placebo capsules containing potassium chloride (KCl) daily for 5 days. The primary endpoint is development of CIN using the Kidney Disease Improving Global Outcomes (KDIGO) criteria. A key secondary endpoint is renal function over a 3-month follow-up period. Additional secondary endpoints include serum renal biomarkers (e.g. neutrophil gelatinase-associated lipocalin) at 6 h, 48 h and 3 months following administration of contrast. Cost-effectiveness of inorganic nitrate therapy will also be evaluated. Summary: This study is designed to investigate the hypothesis that inorganic nitrate treatment decreases the rate of CIN as part of semi-emergent coronary angiography for ACS. Inorganic nitrate is a simple and easy to administer intervention that may prove useful in prevention of CIN in at-risk patients undergoing coronary angiographic procedures

HEROIC: a 5-year observational cohort study aimed at identifying novel factors that drive diabetic kidney disease: rationale and study protocol

Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ. INTRODUCTION: Diabetic kidney disease (DKD) is the leading cause of end-stage kidney disease worldwide and a major cause of premature mortality in diabetes mellitus (DM). While improvements in care have reduced the incidence of kidney disease among those with DM, the increasing prevalence of DM means that the number of patients worldwide with DKD is increasing. Improved understanding of the biology of DKD and identification of novel therapeutic targets may lead to new treatments. A major challenge to progress has been the heterogeneity of the DKD phenotype and renal progression. To investigate the heterogeneity of DKD we have set up The East and North London Diabetes Cohort (HEROIC) Study, a secondary care-based, multiethnic observational study of patients with biopsy-proven DKD. Our primary objective is to identify histological features of DKD associated with kidney endpoints in a cohort of patients diagnosed with type 1 and type 2 DM, proteinuria and kidney impairment. METHODS AND ANALYSIS: HEROIC is a longitudinal observational study that aims to recruit 500 patients with DKD at high-risk of renal and cardiovascular events. Demographic, clinical and laboratory data will be collected and assessed annually for 5 years. Renal biopsy tissue will be collected and archived at recruitment. Blood and urine samples will be collected at baseline and during annual follow-up visits. Measured glomerular filtration rate (GFR), echocardiography, retinal optical coherence tomography angiography and kidney and cardiac MRI will be performed at baseline and twice more during follow-up. The study is 90% powered to detect an association between key histological and imaging parameters and a composite of death, renal replacement therapy or a 30% decline in estimated GFR. ETHICS AND DISSEMINATION: Ethical approval has been obtained from the Bloomsbury Research Ethics Committee (REC 18-LO-1921). Any patient identifiable data will be stored on a password-protected National Health Services N3 network with full audit trail. Anonymised imaging data will be stored in a ISO27001-certificated data warehouse.Results will be reported through peer-reviewed manuscripts and conferences and disseminated to participants, patients and the public using web-based and social media engagement tools as well as through public events

Evidence of a causal and modifiable relationship between kidney function and circulating trimethylamine N-oxide

The host-microbiota co-metabolite trimethylamine N-oxide (TMAO) is linked to increased cardiovascular risk but how its circulating levels are regulated remains unclear. We applied "explainable" machine learning, univariate, multivariate and mediation analyses of fasting plasma TMAO concentration and a multitude of phenotypes in 1,741 adult Europeans of the MetaCardis study. Here we show that next to age, kidney function is the primary variable predicting circulating TMAO, with microbiota composition and diet playing minor, albeit significant, roles. Mediation analysis suggests a causal relationship between TMAO and kidney function that we corroborate in preclinical models where TMAO exposure increases kidney scarring. Consistent with our findings, patients receiving glucose-lowering drugs with reno-protective properties have significantly lower circulating TMAO when compared to propensity-score matched control individuals. Our analyses uncover a bidirectional relationship between kidney function and TMAO that can potentially be modified by reno-protective anti-diabetic drugs and suggest a clinically actionable intervention for decreasing TMAO-associated excess cardiovascular risk

Ethnic/Race Diversity and Diabetic Kidney Disease

Ethnicity and race are often used interchangeably in the literature. However, the traditional definition of race and ethnicity is related to biological (bone structure and skin, hair, or eye color) and sociological factors (nationality, regional culture, ancestry, and language) respectively. Diabetes mellitus (DM) is a huge global public health problem. As the number of individuals with Type 2 DM grows, the prevalence of diabetic kidney disease (DKD), which is one of the most serious complications, is expected to rise sharply. Many ethnic and racial groups have a greater risk of developing DM and its associated macro and micro-vascular complications

Systematic Review and the External Validity of Randomized Controlled Trials in Lupus Nephritis

Randomized controlled trials (RCTs) are considered the gold standard for assessing treatment efficacy. However, sampling bias can affect the generalization of results to routine clinical practice. Here we assessed whether patients with lupus nephritis (LN) seen in routine clinical practice would have satisfied entry criteria to the major published RCTs in LN. Methods: A systematic literature search from January 1974 to May 2015 was carried out, identifying all RCTs investigating LN induction treatment. Patients diagnosed with proliferative or membranous LN between 1995 and 2013 were identified from the Barts Lupus Centre database; baseline characteristics were compared with each RCT’s entry criteria to assess hypothetical inclusion or exclusion. Results: Of 363 articles, 33 RCTs met inclusion criteria. Of 137 patients newly diagnosed with LN (111 with proliferative/mixed proliferative and 26 with pure membranous LN), 32% would have been excluded from RCT entry (range 8%–73%). The main reasons for exclusion would have been too severe disease, too mild disease, or prior immunosuppressant use, which were exclusion criteria in 26, 20, and 22 RCTs, respectively. A total of 27 patients with LN (20%) were re-biopsied due to flare; 68% of these would have been ineligible to enter RCTs. Conclusion: Published RCTs do not truly reflect the heterogeneity of patients with LN in routine practice at our lupus center. The external validity of RCTs could be improved by including more representative patient cohorts. RCTs should be used as a guide but consideration should be given to similarities between individual patients and the characteristics of the trial cohorts before treatment decisions being made

Data from: Is lack of suitable housing a barrier to home-based dialysis therapy for patients with end-stage renal disease? A cohort study

Objective: To determine whether inadequate housing is the main barrier to the provision of home dialysis treatment. Design: Prospective observational study. Participants: All patients attending a predialysis clinic between 2006 and 2009 deemed medically suitable for home dialysis and not active on the preemptive transplant list. Setting: A predialysis clinic in a London teaching hospital. Main outcome measure: Assessment of patient's accommodation for suitability for home-based dialysis using departmental guidelines and the Government's Housing Health and Safety Rating System regulations 2005. Results: A lack of adequate housing prohibited the provision of home haemodialysis to all but one of these patients. Moreover, only 29% of homes assessed were suitable for peritoneal dialysis, despite the lower spatial demands of this form of renal replacement therapy. In addition to the specific requirements of dialysis, we also found that only 33% of the homes visited fulfilled the minimum standard of housing as defined in the Government's Decent Homes Standard, with multiple specific hazards identified across the properties. Conclusions: This study illustrates that the lack of suitable housing is a major barrier to the provision of home-based dialysis and underscores the need for this to be addressed urgently at both the central government and local authority levels. We suggest that it should be considered as a major priority to rehouse medically suitable patients with a view to enabling home-based therapy

A systematic review and meta-analysis of the evidence on inflammation in depressive illness and symptoms in chronic and end-stage kidney disease

BACKGROUND: Depression affects approximately 27% of adults with chronic kidney disease (CKD) and end-stage kidney failure (ESKF). Depression in this population is associated with impaired quality of life and increased mortality. The extent of inflammation and the impact on depression in CKD/ESKF is yet to be established. Through a systematic literature review and meta-analysis, we aim to understand the relationship between depression and inflammation in CKD/ESKF patients.METHODS: We searched nine electronic databases for published studies until January 2022. Titles and abstracts were screened against inclusion and exclusion criteria. Data extraction and study quality assessment was carried out independently by two reviewers. A meta-analysis was carried out where appropriate; otherwise a narrative review of studies was completed.RESULTS: Sixty studies met our inclusion criteria and entered the review (9481 patients included in meta-analysis). Meta-analysis of cross-sectional associations revealed significantly higher levels of pro-inflammatory biomarkers; C-reactive protein; Interleukin 6 (IL-6) and tumour necrosis factor-alpha in patients with depressive symptoms (DS) compared to patients without DS. Significantly lower levels of anti-inflammatory cytokine IL-10 were found in patients with DS compared to patients without DS. Considerable heterogeneity was detected in the analysis for most inflammatory markers.CONCLUSION: We found evidence for an association of higher levels of pro-inflammatory and lower anti-inflammatory cytokines and DS in patients with CKD/ESKF. Clinical trials are needed to investigate whether anti-inflammatory therapies will be effective in the prevention and treatment of DS in these patients with multiple comorbidities.</p

final hhd data for submission

Table of all patients included for home visits. Patients were identified by date of birth and hospital number which have been removed for confidentiality. Data extracted from our renal database. Outcome of visits supplied by renal social worker and predialysis nurse from logged home visits. Race as stated by patient. DM refers to diabetic or not, RRT refers to the modality of renal replacement implemented following home visit, DHS relates to whether home met basic government standards, HHSR code lists specific hazards in the home (max 4 per home listed) and temp accom refers to whether the accomodation was of a temporary nature, With regards RRT, APD donates automated peritoneal dialysis, CAPD continual ambulatory peritoneal dialysis, HD haemodialysis and the various initials following HD refer to the different renal units within out catchment