Can remote testing for chronic kidney disease improve outcomes without widening existing health inequalities? A collaborative quality improvement project in primary care.

BACKGROUND: In the UK, chronic kidney disease (CKD) is a prevalent, silent and strong predictor of cardiovascular disease. Identification of CKD is poor in primary care, particularly in minority ethnic and socio-economically deprived groups. AIM: To investigate feasibility of remote ACR testing to improve the detection and management of CKD in underserved groups. METHOD: 13 591 tests were sent out across South East London. Individuals with diabetes and no ACR in the past year were offered a remote ACR test to complete at home with a smartphone using a validated app (Healthy.io). We extracted data on demographics, medical comorbidities and medication. Analyses (Stata) describe who completed the test. RESULTS: Twenty-seven practices agreed to participate. Analyses of 6082 tests sent show the test completion rate was 46.8%. Adjusted odds ratios demonstrated that people were less likely to complete testing if over 70 years (OR 0.71, 95% CI 0.57 to 0.89) and over 80 (OR 0.43, CI 95% 0.33 to 0.56) compared to <40 years old; people from CORE20 groups (most deprived quintile) were also less likely to complete testing (OR 0.68, 95% CI 0.61 to 0.76) and those with missing data and those with no recorded healthcare interactions within the last 5 years were also less likely to complete testing. DISCUSSION: Remote ACR testing presents an opportunity to diagnose early CKD but there is still inequity in who completes testing. Engagement with stakeholders is needed to explore innovative ways to implement remote ACR testing to achieve equitable CKD screening.

Performance and pitfalls of the tools for measuring glomerular filtration rate to guide chronic kidney disease diagnosis and assessment.

Accurate diagnosis, classification and risk stratification for chronic kidney disease (CKD) allow for early recognition and delivering optimal care. Creatinine-based glomerular filtration rate (GFR), urinary albumin: creatinine ratio (UACR) and the kidney failure risk equation (KFRE) are important tools to achieve this, but understanding their limitations is important for optimal implementation.When accurate GFR is required (eg, chemotherapy dosing), GFR is measured using an exogenous filtration marker. In routine clinical practice, in contrast, estimated GFR (eGFR) from serum creatinine (SCr), calculated using the enzymatic method±UACR, is recommended. Limitations of SCr include non-GFR determinants such as muscle mass, diet and tubular handling. An alternative or additional endogenous filtration marker is cystatin C, which can be used alongside SCr for confirmatory testing of CKD. However, its role in the UK is more limited due to concerns regarding false positive results.The recommended creatinine-based eGFR equation in the UK is the CKD Epidemiology Collaboration 2009 equation. This was recently updated to a race-neutral 2021 version and demonstrated reduced bias in people of Black ethnicity, but has not been validated in the UK. Limitations are extremes of age, inaccuracy at greater GFRs and reduced generalisability to under-represented ethnicity groups.The KFRE (based on age, sex, SCr and UACR) has recently been developed to help determine 2-year and 5-year risk of progression to end-stage kidney disease. It has been validated in over 30 countries and provides meaningful quantitative information to patients. However, supporting evidence for their performance in ethnic minority groups and kidney diseases such as glomerulonephritis remains modest.In conclusion, early identification, risk stratification of kidney disease and timely intervention are important to impact kidney disease progression. However, clinician awareness of the limitations and variability of creatinine, cystatin C and the eGFR equations, is key to appropriate interpretation of results.

Estimated glomerular filtration rate equations in people of self-reported black ethnicity in the United Kingdom: Inappropriate adjustment for ethnicity may lead to reduced access to care.

Assessment in African populations suggest adjustment for ethnicity in estimated glomerular filtration rate (eGFR) equations derived from African Americans lead to overestimation of GFR and failure to determine severity in chronic kidney disease (CKD). However, studies in African Europeans are limited. We aimed to assess accuracy of eGFR equations, with and without ethnicity adjustment compared with measured GFR in people of Black ethnicity in the United Kingdom. Performance of MDRD, CKD-EPI (with and without ethnicity adjustment), Full Age Spectrum (FAS), revised Lund Malmö (LM Revised), and European Kidney Function Consortium (EKFC) eGFR equations were assessed compared to 51Cr-EDTA GFR studies extracted from hospital databases. Participants with albumin <30g/l, liver disease, <18 years, of non-Black or non-White self-reported ethnicity were excluded. Agreement was assessed by bias, precision and 30%-accuracy and was stratified for ethnicity and GFR. 1888 51Cr-EDTA studies were included (Mean age-53.7yrs; 43.6% female; 14.1% Black ethnicity). Compared to White participants, eGFR-MDRD and eGFR-CKD-EPI equations in Black participants significantly overestimated GFR (bias 20.3 and 19.7 ml/min/1.73m2 respectively, p<0.001). Disregarding the ethnicity adjustment significantly improved GFR estimates for Black participants (bias 6.7 and 2.4ml/min/1.73m2 for eGFR-MDRD and eGFR-CKD-EPI respectively, p<0.001). The LM Revised equation had the smallest bias for both White and Black participants (5.8ml and -1.1ml/min/1.73m2 respectively). 30%-accuracy was superior for GFR≥60ml/min/1.73m2 compared to <60ml/min/1.73m2 using eGFR-CKD-EPI equation for both White and Black participants (p<0.001). Multivariate regression methodology with adjustment for age, sex and log(serum creatinine) in the cohort yielded an ethnicity coefficient of 1.018 (95% CI: 1.009-1.027). Overestimation of measured GFR with eGFR equations using ethnicity adjustment factors may lead to reduced CKD diagnosis and under-recognition of severity in people of Black ethnicity. Our findings suggest that ethnicity adjustment for GFR estimation in non-African Americans may not be appropriate for use in people of Black ethnicity in the UK.

The NIH-NIAID Filariasis Research Reagent Resource Center.

Filarial worms cause a variety of tropical diseases in humans; however, they are difficult to study because they have complex life cycles that require arthropod intermediate hosts and mammalian definitive hosts. Research efforts in industrialized countries are further complicated by the fact that some filarial nematodes that cause disease in humans are restricted in host specificity to humans alone. This potentially makes the commitment to research difficult, expensive, and restrictive. Over 40 years ago, the United States National Institutes of Health-National Institute of Allergy and Infectious Diseases (NIH-NIAID) established a resource from which investigators could obtain various filarial parasite species and life cycle stages without having to expend the effort and funds necessary to maintain the entire life cycles in their own laboratories. This centralized resource (The Filariasis Research Reagent Resource Center, or FR3) translated into cost savings to both NIH-NIAID and to principal investigators by freeing up personnel costs on grants and allowing investigators to divert more funds to targeted research goals. Many investigators, especially those new to the field of tropical medicine, are unaware of the scope of materials and support provided by the FR3. This review is intended to provide a short history of the contract, brief descriptions of the fiilarial species and molecular resources provided, and an estimate of the impact the resource has had on the research community, and describes some new additions and potential benefits the resource center might have for the ever-changing research interests of investigators.

Using an intravenous catheter to carry out abdominal lavage in the gerbil.

Abdominal lavage is used in laboratory rodents for a variety of applications but carries an inherent risk of abdominal organ laceration; therefore, personnel carrying out this procedure must have considerable expertise. In this paper, the authors describe an improved method for delivering sterile media to and collecting peritoneal fluids from dark-clawed Mongolian gerbils (Meriones unguiculatus) that had been peritoneally infected with filarial nematode parasites (genus Brugia). To carry out this gravity-assisted technique, the authors used a catheter to introduce sterile media into the peritoneal cavity of each gerbil and then to passively drain peritoneal fluid and larval worms for collection. Average fluid recovery was consistently greater when using this gravity-assisted method than when using aspiration. Larval parasites were recovered by both methods. To recover large volumes of fluid using the standard method of abdominal lavage, personnel typically must euthanize rodents. This gravity-assisted technique allows researchers to collect large numbers of parasite larvae without euthanizing gerbils.

Use of microarray hybridization to identify Brugia genes involved in mosquito infectivity.

Brugia malayi and Brugia pahangi microfilariae (mf) require a maturation period of at least 5 days in the mammalian host to successfully infect laboratory mosquitoes. This maturation process coincides with changes in the surface composition of mf that likely are associated with changes in gene expression. To test this hypothesis, we verified the differential infectivity of immature (< or =3 day) and mature (>30 day) Brugia mf for black-eyed Liverpool strain of Aedes aegypti and then assessed transcriptome changes associated with microfilarial maturation by competitively hybridizing microfilarial cDNAs to the B. malayi oligonucleotide microarray. We identified transcripts differentially abundant in immature (94 in B. pahangi and 29 in B. malayi) and mature (64 in B. pahangi and 14 in B. malayi) mf. In each case, >40% of Brugia transcripts shared no similarity to known genes or were similar to genes with unknown function; the remaining transcripts were categorized by putative function based on sequence similarity to known genes/proteins. Microfilarial maturation was not associated with demonstrable changes in the abundance of transmembrane or secreted proteins; however, immature mf expressed more transcripts associated with immune modulation, neurotransmission, transcription, and cellular cytoskeleton elements, while mature mf displayed increased transcripts potentially encoding hypodermal/muscle and surface molecules, e.g., cuticular collagens and sheath components. The results of the homologous B. malayi microarray hybridization were validated by quantitative reverse transcriptase polymerase chain reaction. These findings preliminarily lend support to the underlying hypothesis that changes in microfilarial gene expression drive maturation-associated changes that influence the parasite to develop in compatible vectors.

Digoxin-carvedilol interactions in children.

Digoxin is often coadministered with carvedilol in children with severe ventricular failure. In eight children (age 2 weeks to 8 years), the oral clearance of digoxin decreased by half with carvedilol, and two of them had digoxin toxicity. Carvedilol increases serum concentrations of digoxin in children, and its dose may need to be reduced to avoid toxicity.