Anemia in Pregnancy With CKD.

Chronic kidney disease (CKD), anemia, and iron deficiency are global health issues affecting individuals in both high-income and low-income countries. In pregnancy, both CKD and iron deficiency anemia increase the risk of adverse maternal and neonatal outcomes, including increased maternal morbidity and mortality, stillbirth, perinatal death, preterm birth, and low birthweight. However, it is unknown to which extent iron deficiency anemia contributes to adverse outcomes in CKD pregnancy. Furthermore, little is known regarding the prevalence, pathophysiology, and treatment of iron deficiency and anemia in pregnant women with CKD. Therefore, there are many unanswered questions regarding optimal management with oral or i.v. iron and recombinant human erythropoietin (rhEPO) in these women. In this review, we present a short overview of the (patho)physiology of anemia in healthy pregnancy and in people living with CKD. We present an evaluation of the literature on iron deficiency, anemia, and nutritional deficits in pregnant women with CKD; and we evaluate current knowledge gaps. Finally, we propose research priorities regarding anemia in pregnant women with CKD.

Utility of the Venous Excess Ultrasound (VEXUS) score to track dynamic change in volume status in patients undergoing fluid removal during haemodialysis - the ACUVEX study.

BACKGROUND: The use of ultrasound assessment, including the Venous Excess Ultrasound (VEXUS) score, is increasingly being utilised as part of fluid status assessment in clinical practice. We aimed to evaluate the ability of the VEXUS score to track fluid removal during the course of the dialysis session and explore the relationship between traditional measures of fluid status and venous congestion. METHODS: Single-centre, observational study in patients undergoing intermittent haemodialysis, who presented above their target dry weight. Patients had serial assessment using VEXUS, lung ultrasound and selected echocardiographic measures, before, during and after fluid removal. RESULTS: Amongst 33 patients analysed, 5 (15%) had an elevated VEXUS score (> 0). There was no difference in starting weight, dry weight or amount of fluid removed in patients with a normal VEXUS score and those with an elevated VEXUS score. In all patients with elevated VEXUS scores, the degree of venous congestion improved during the course of fluid removal. All patients with an elevated VEXUS score had evidence of both right and left ventricular systolic impairment. CONCLUSION: In patients with ESRF undergoing haemodialysis, the incidence of venous congestion as measured by the VEXUS is low. In patients with elevated VEXUS scores, removal of fluid through haemodialysis improves the venous congestion score. The pattern of LV and RV systolic dysfunction suggests that VEXUS may be a reflection of cardiac failure rather than venous volume status. TRIAL REGISTRATION: Ethical approval was provided by South Central-Berkshire Research and Ethics Committee and registered on clinicaltrials.org (IRAS305720). TRIAL REGISTRATION: ISRCTN14351189 - Retrospectively registered on 30/11/2023.

Effects of rare kidney diseases on kidney failure: a longitudinal analysis of the UK National Registry of Rare Kidney Diseases (RaDaR) cohort.

BACKGROUND: Individuals with rare kidney diseases account for 5-10% of people with chronic kidney disease, but constitute more than 25% of patients receiving kidney replacement therapy. The National Registry of Rare Kidney Diseases (RaDaR) gathers longitudinal data from patients with these conditions, which we used to study disease progression and outcomes of death and kidney failure. METHODS: People aged 0-96 years living with 28 types of rare kidney diseases were recruited from 108 UK renal care facilities. The primary outcomes were cumulative incidence of mortality and kidney failure in individuals with rare kidney diseases, which were calculated and compared with that of unselected patients with chronic kidney disease. Cumulative incidence and Kaplan-Meier survival estimates were calculated for the following outcomes: median age at kidney failure; median age at death; time from start of dialysis to death; and time from diagnosis to estimated glomerular filtration rate (eGFR) thresholds, allowing calculation of time from last eGFR of 75 mL/min per 1·73 m2 or more to first eGFR of less than 30 mL/min per 1·73 m2 (the therapeutic trial window). FINDINGS: Between Jan 18, 2010, and July 25, 2022, 27 285 participants were recruited to RaDaR. Median follow-up time from diagnosis was 9·6 years (IQR 5·9-16·7). RaDaR participants had significantly higher 5-year cumulative incidence of kidney failure than 2·81 million UK patients with all-cause chronic kidney disease (28% vs 1%; p<0·0001), but better survival rates (standardised mortality ratio 0·42 [95% CI 0·32-0·52]; p<0·0001). Median age at kidney failure, median age at death, time from start of dialysis to death, time from diagnosis to eGFR thresholds, and therapeutic trial window all varied substantially between rare diseases. INTERPRETATION: Patients with rare kidney diseases differ from the general population of individuals with chronic kidney disease: they have higher 5-year rates of kidney failure but higher survival than other patients with chronic kidney disease stages 3-5, and so are over-represented in the cohort of patients requiring kidney replacement therapy. Addressing unmet therapeutic need for patients with rare kidney diseases could have a large beneficial effect on long-term kidney replacement therapy demand. FUNDING: RaDaR is funded by the Medical Research Council, Kidney Research UK, Kidney Care UK, and the Polycystic Kidney Disease Charity.

Adverse pregnancy outcomes in pregnant women with chronic kidney disease: A systematic review and meta-analysis.

BACKGROUND: Chronic kidney disease (CKD) is associated with an increased risk of adverse pregnancy outcomes, but the risk at different stages of CKD (defined by estimated glomerular filtration rate, eGFR) compared with women without CKD has not been quantified in large cohorts. OBJECTIVES: To quantify the association between CKD and adverse pregnancy outcomes according to CKD definition, CKD stage and presence or absence of diabetes. SEARCH STRATEGY: A systematic search of EMBASE and MEDLINE from inception to 5 January 2023. SELECTION CRITERIA: English-language randomised controlled trials as well as cohort and case-control studies investigating adverse pregnancy outcomes in pregnant women with CKD. DATA COLLECTION AND ANALYSIS: Two reviewers conducted independent data extractions. A random-effects model was used to estimate risk. MAIN RESULTS: We included 19 studies with 3 251 902 women. Defining CKD using eGFR or serum creatinine produced results with greater effect size but wider confidence intervals. Compared with CKD stages 1-2, women with CKD stages 3-5 have a greater risk, but also greater imprecision in the risk estimate, of the following outcomes: pre-eclampsia (OR 55.18, 95% CI 2.63-1157.68, vs OR 24.74, 95% CI 1.75-348.70), preterm birth (OR 20.24, 95% CI 2.85-143.75, vs OR 8.18, 95% CI 1.54-43.46) and neonatal intensive care unit admission (OR 19.32, 95% CI 3.07-121.68, vs OR 9.77, 95% CI 2.49-38.39). Women with diabetic kidney disease, compared with women without diabetic kidney disease, have higher risks of maternal mortality, small-for-gestational-age neonates, pre-eclampsia and gestational hypertension. CONCLUSIONS: There is heterogeneity in the definition of CKD in pregnancy. Future studies should consider ways to standardise its definition and measurement in pregnancy.

Reassuring pregnancy outcomes in women with mild COL4A3-5-related disease (Alport syndrome) and genetic type of disease can aid personalized counseling.

Individualized pre-pregnancy counseling and antenatal care for women with chronic kidney disease (CKD) require disease-specific data. Here, we investigated pregnancy outcomes and long-term kidney function in women with COL4A3-5 related disease (Alport Syndrome, (AS)) in a large multicenter cohort. The ALPART-network (mAternaL and fetal PregnAncy outcomes of women with AlpoRT syndrome), an international collaboration of 17 centers, retrospectively investigated COL4A3-5 related disease pregnancies after the 20th week. Outcomes were stratified per inheritance pattern (X-Linked AS (XLAS)), Autosomal Dominant AS (ADAS), or Autosomal Recessive AS (ARAS)). The influence of pregnancy on estimated glomerular filtration rate (eGFR)-slope was assessed in 192 pregnancies encompassing 116 women (121 with XLAS, 47 with ADAS, and 12 with ARAS). Median eGFR pre-pregnancy was over 90ml/min/1.73m2. Neonatal outcomes were favorable: 100% live births, median gestational age 39.0 weeks and mean birth weight 3135 grams. Gestational hypertension occurred during 23% of pregnancies (reference: 'general' CKD G1-G2 pregnancies incidence is 4-20%) and preeclampsia in 20%. The mean eGFR declined after pregnancy but remained within normal range (over 90ml/min/1.73m2). Pregnancy did not significantly affect eGFR-slope (pre-pregnancy ß=-1.030, post-pregnancy ß=-1.349). ARAS-pregnancies demonstrated less favorable outcomes (early preterm birth incidence 3/11 (27%)). ARAS was a significant independent predictor for lower birth weight and shorter duration of pregnancy, next to the classic predictors (pre-pregnancy kidney function, proteinuria, and chronic hypertension) though missing proteinuria values and the small ARAS-sample hindered analysis. This is the largest study to date on AS and pregnancy with reassuring results for mild AS, though inheritance patterns could be considered in counseling next to classic risk factors. Thus, our findings support personalized reproductive care and highlight the importance of investigating kidney disease-specific pregnancy outcomes.

The development and internal pilot trial of a digital physical activity and emotional well-being intervention (Kidney BEAM) for people with chronic kidney disease.

This trial assessed the feasibility and acceptability of Kidney BEAM, a physical activity and emotional well-being self-management digital health intervention (DHI) for people with chronic kidney disease (CKD), which offers live and on-demand physical activity sessions, educational blogs and videos, and peer support. In this mixed-methods, multicentre randomised waitlist-controlled internal pilot, adults with established CKD were recruited from five NHS hospitals and randomised 1:1 to Kidney BEAM or waitlist control. Feasibility outcomes were based upon a priori progression criteria. Acceptability was primarily explored via individual semi-structured interviews (n = 15). Of 763 individuals screened, n = 519 (68%, 95% CI 65 to 71%) were eligible. Of those eligible, n = 303 (58%, 95% CI 54-63%) did not respond to an invitation to participate by the end of the pilot period. Of the 216 responders, 50 (23%, 95% CI 18-29%) consented. Of the 42 randomised, n = 22 (10 (45%) male; 49 ± 16 years; 14 (64%) White British) were allocated to Kidney BEAM and n = 20 (12 (55%) male; 56 ± 11 years; 15 (68%) White British) to the waitlist control group. Overall, n = 15 (30%, 95% CI 18-45%) withdrew during the pilot phase. Participants completed a median of 14 (IQR 5-21) sessions. At baseline, 90-100% of outcome data (patient reported outcome measures and a remotely conducted physical function test) were completed and 62-83% completed at 12 weeks follow-up. Interview data revealed that remote trial procedures were acceptable. Participants' reported that Kidney BEAM increased their opportunity and motivation to be physically active, however, lack of time remained an ongoing barrier to engagement with the DHI. An randomised controlled trial of Kidney BEAM is feasible and acceptable, with adaptations to increase recruitment, retention and engagement.Trial registration NCT04872933. Date of first registration 05/05/2021.

Pregnancy-associated changes in urinary uromodulin excretion in chronic hypertension.

BACKGROUND: Pregnancy involves major adaptations in renal haemodynamics, tubular, and endocrine functions. Hypertensive disorders of pregnancy are a leading cause of maternal mortality and morbidity. Uromodulin is a nephron-derived protein that is associated with hypertension and kidney diseases. Here we study the role of urinary uromodulin excretion in hypertensive pregnancy. METHODS: Urinary uromodulin was measured by ELISA in 146 pregnant women with treated chronic hypertension (n = 118) and controls (n = 28). We studied non-pregnant and pregnant Wistar Kyoto and Stroke Prone Spontaneously Hypertensive rats (n = 8/strain), among which a group of pregnant Stroke-Prone Spontaneously Hypertensive rats was treated with either nifedipine (n = 7) or propranolol (n = 8). RESULTS: In pregnant women, diagnosis of chronic hypertension, increased maternal body mass index, Black maternal ethnicity and elevated systolic blood pressure at the first antenatal visit were significantly associated with a lower urinary uromodulin-to-creatinine ratio. In rodents, pre-pregnancy urinary uromodulin excretion was twofold lower in Stroke-Prone Spontaneously Hypertensive rats than in Wistar Kyoto rats. During pregnancy, the urinary uromodulin excretion rate gradually decreased in Wistar Kyoto rats (a twofold decrease), whereas a 1.5-fold increase was observed in Stroke-Prone Spontaneously Hypertensive rats compared to pre-pregnancy levels. Changes in uromodulin were attributed by kidney injury in pregnant rats. Neither antihypertensive changed urinary uromodulin excretion rate in pregnant Stroke-Prone Spontaneously Hypertensive rats. CONCLUSIONS: In summary, we demonstrate pregnancy-associated differences in urinary uromodulin: creatinine ratio and uromodulin excretion rate between chronic hypertensive and normotensive pregnancies. Further research is needed to fully understand uromodulin physiology in human pregnancy and establish uromodulin's potential as a biomarker for renal adaptation and renal function in pregnancy.

Evaluating the effect of a digital health intervention to enhance physical activity in people with chronic kidney disease (Kidney BEAM): a multicentre, randomised controlled trial in the UK.

BACKGROUND: Remote digital health interventions to enhance physical activity provide a potential solution to improve the sedentary behaviour, physical inactivity, and poor health-related quality of life that are typical of chronic conditions, particularly for people with chronic kidney disease. However, there is a need for high-quality evidence to support implementation in clinical practice. The Kidney BEAM trial evaluated the clinical effect of a 12-week physical activity digital health intervention on health-related quality of life. METHODS: In a single-blind, randomised controlled trial conducted at 11 centres in the UK, adult participants (aged ≥18 years) with chronic kidney disease were recruited and randomly assigned (1:1) to the Kidney BEAM physical activity digital health intervention or a waiting list control group. Randomisation was performed with a web-based system, in randomly permuted blocks of six. Outcome assessors were masked to treatment allocation. The primary outcome was the difference in the Kidney Disease Quality of Life Short Form version 1.3 Mental Component Summary (KDQoL-SF1.3 MCS) between baseline and 12 weeks. The trial was powered to detect a clinically meaningful difference of 3 arbitrary units (AU) in KDQoL-SF1.3 MCS. Outcomes were analysed by an intention-to-treat approach using an analysis of covariance model, with baseline measures and age as covariates. The trial was registered with ClinicalTrials.gov, NCT04872933. FINDINGS: Between May 6, 2021, and Oct 30, 2022, 1102 individuals were assessed for eligibility, of whom 340 participants were enrolled and randomly assigned to the Kidney BEAM intervention group (n=173) or the waiting list control group (n=167). 268 participants completed the trial (112 in the Kidney BEAM group and 156 in the waiting list control group). All 340 randomly assigned participants were included in the intention-to treat population. At 12 weeks, there was a significant improvement in KDQoL-SF.13 MCS score in the Kidney BEAM group (from mean 44·6 AU [SD 10·8] at baseline to 47·0 AU [10·6] at 12 weeks) compared with the waiting list control group (from 46·1 AU [10·5] to 45·0 AU [10·1]; between-group difference of 3·1 AU [95% CI 1·8-4·4]; p<0·0001). INTERPRETATION: The Kidney BEAM physical activity platform is an efficacious digital health intervention to improve mental health-related quality of life in patients with chronic kidney disease. These findings could facilitate the incorporation of remote digital health interventions into clinical practice and offer a potential intervention worthy of investigation in other chronic conditions. FUNDING: Kidney Research UK.

Female Infertility in Chronic Kidney Disease.

This review summarises the current literature regarding infertility in women with chronic kidney disease (CKD), describing the epidemiology, pathophysiology, investigations, and management options. The pathophysiology is multifactorial, with proposed mechanisms including disruption of the hypothalamus-pituitary-ovarian axis, chronic inflammation, oxidative stress, psychological factors, and gonadotoxic effects of medications such as cyclophosphamide. Diagnostic investigations in CKD patients seeking to conceive should be considered earlier than in the healthy population. Investigations should include hormonal profiling, including markers such as Anti-Mullerian Hormone and imaging such as ultrasound, to evaluate ovarian reserve and identify gynaecology pathology. Treatment options for infertility in CKD patients include GnRH agonists to preserve ovarian function during cyclophosphamide treatment, as well as assisted reproductive technologies including in vitro fertilisation and ovulation induction. However, these treatments must be tailored to the individual's health status, comorbidities, fertility requirements, and CKD stage. In conclusion, fertility is an important consideration for women with CKD, necessitating early investigation and tailored management. Early discussions regarding fertility are important in order to understand patients' family planning and allow for prompt referral to fertility services. While challenges exist, ongoing research aims to clarify the underlying mechanism and optimise treatment strategies, which are crucial for improving quality of life and overall health outcomes.

CRADLE-5: a stepped-wedge type 2 hybrid implementation-effectiveness cluster randomised controlled trial to evaluate the real-world scale-up of the CRADLE Vital Signs Alert intervention into routine maternity care in Sierra Leone-study protocol.

BACKGROUND: The CRADLE Vital Signs Alert intervention (an accurate easy-to-use device that measures blood pressure and pulse with inbuilt traffic-light early warning system, and focused training package) was associated with reduced rates of eclampsia and maternal death when trialled in urban areas in Sierra Leone. Subsequently, implementation was successfully piloted as evidenced by measures of fidelity, feasibility and adoption. The CRADLE-5 trial will examine whether national scale-up, including in the most rural areas, will reduce a composite outcome of maternal and fetal mortality and maternal morbidity and will evaluate how the CRADLE package can be embedded sustainably into routine clinical pathways. METHODS: CRADLE-5 is a stepped-wedge cluster-randomised controlled trial of the CRADLE intervention compared to routine maternity care across eight rural districts in Sierra Leone (Bonthe, Falaba, Karene, Kailahun, Koinadugu, Kono, Moyamba, Tonkolili). Each district will cross from control to intervention at six-weekly intervals over the course of 1 year (May 2022 to June 2023). All women identified as pregnant or within six-weeks postpartum presenting for maternity care in the district are included. Primary outcome data (composite rate of maternal death, stillbirth, eclampsia and emergency hysterectomy) will be collected. A mixed-methods process and scale-up evaluation (informed by Medical Research Council guidance for complex interventions and the World Health Organization ExpandNet tools) will explore implementation outcomes of fidelity, adoption, adaptation and scale-up outcomes of reach, maintenance, sustainability and integration. Mechanisms of change and contextual factors (barriers and facilitators) will be assessed. A concurrent cost-effectiveness analysis will be undertaken. DISCUSSION: International guidance recommends that all pregnant and postpartum women have regular blood pressure assessment, and healthcare staff are adequately trained to respond to abnormalities. Clinical effectiveness to improve maternal and perinatal health in more rural areas, and ease of integration and sustainability of the CRADLE intervention at scale has yet to be investigated. This trial will explore whether national scale-up of the CRADLE intervention reduces maternal and fetal mortality and severe maternal adverse outcomes and understand the strategies for adoption, integration and sustainability in low-resource settings. If successful, the aim is to develop an adaptable, evidence-based scale-up roadmap to improve maternal and infant outcomes. TRIAL REGISTRATION: ISRCTN 94429427. Registered on 20 April 2022.

A Randomized Trial of Intravenous Iron Supplementation and Exercise on Exercise Capacity in Iron-Deficient Nonanemic Patients With CKD.

Introduction: Patients with chronic kidney disease (CKD) are often iron deficient, even when not anemic. This trial evaluated whether iron supplementation enhances exercise capacity of nonanemic patients with CKD who have iron-deficiency. Methods: Prospective, multicenter double-blind randomized controlled trial of nondialysis patients with CKD and iron-deficiency but without anemia (Hemoglobin [Hb] >110 g/l). Patients were assigned 1:1 to intravenous (IV) iron therapy, or placebo. An 8-week exercise program commenced at week 4. The primary outcome was the mean between-group difference in 6-minute walk test (6MWT) at 4 weeks. Secondary outcomes included 6MWT at 12 weeks, transferrin saturation (TSAT), serum ferritin (SF), Hb, renal function, muscle strength, functional capacity, quality of life, and adverse events at baseline, 4 weeks, and at 12 weeks. Mean between-group differences were analyzed using analysis of covariance models. Results: Among 75 randomized patients, mean (SD) age for iron therapy (n = 37) versus placebo (n = 38) was 54 (16) versus 61 (12) years; estimated glomerular filtration rate (eGFR) (34 [12] vs. 35 [11] ml/min per 1.73 m2], TSAT (23 [12] vs. 21 [6])%; SF (57 [64] vs. 62 [33]) µg/l; Hb (122.4 [9.2] vs. 127 [13.2] g/l); 6MWT (384 [95] vs. 469 [142] meters) at baseline, respectively. No significant mean between-group difference was observed in 6MWT distance at 4 weeks. There were significant increases in SF and TSAT at 4 and 12 weeks (P < 0.02), and Hb at 12 weeks (P = 0.009). There were no between-group differences in other secondary outcomes and no adverse events attributable to iron therapy. Conclusion: This trial did not demonstrate beneficial effects of IV iron therapy on exercise capacity at 4 weeks. A larger study is needed to confirm if IV iron is beneficial in nondialysis patients with CKD who are iron-deficient.

The NightLife study - the clinical and cost-effectiveness of thrice-weekly, extended, in-centre nocturnal haemodialysis versus daytime haemodialysis using a mixed methods approach: study protocol for a randomised controlled trial.

BACKGROUND: In-centre nocturnal haemodialysis (INHD) offers extended-hours haemodialysis, 6 to 8 h thrice-weekly overnight, with the support of dialysis specialist nurses. There is increasing observational data demonstrating potential benefits of INHD on health-related quality of life (HRQoL). There is a lack of randomised controlled trial (RCT) data to confirm these benefits and assess safety. METHODS: The NightLife study is a pragmatic, two-arm, multicentre RCT comparing the impact of 6 months INHD to conventional haemodialysis (thrice-weekly daytime in-centre haemodialysis, 3.5-5 h per session). The primary outcome is the total score from the Kidney Disease Quality of Life tool at 6 months. Secondary outcomes include sleep and cognitive function, measures of safety, adherence to dialysis and impact on clinical parameters. There is an embedded Process Evaluation to assess implementation, health economic modelling and a QuinteT Recruitment Intervention to understand factors that influence recruitment and retention. Adults (≥ 18 years old) who have been established on haemodialysis for > 3 months are eligible to participate. DISCUSSION: There are 68,000 adults in the UK that need kidney replacement therapy (KRT), with in-centre haemodialysis the treatment modality for over a third of cases. HRQoL is an independent predictor of hospitalisation and mortality in individuals on maintenance dialysis. Haemodialysis is associated with poor HRQoL in comparison to the general population. INHD has the potential to improve HRQoL. Vigorous RCT evidence of effectiveness is lacking. The NightLife study is an essential step in the understanding of dialysis therapies and will guide patient-centred decisions regarding KRT in the future. TRIAL REGISTRATION: Trial registration number: ISRCTN87042063. Registered: 14/07/2020.

Improving kidney care for people with severe mental health difficulties: a thematic analysis of twenty-two healthcare providers' perspectives.

Introduction: People with severe mental health difficulties (SMHDs) and concurrent kidney disease have less access to quality kidney care and worse clinical outcomes. Our research investigates the barriers and facilitators to effective kidney care for people with SMHDs, and how care might be improved for this underserved population. Methods: We conducted semi-structured interviews with twenty-two physical (n = 14) and mental (n = 8) healthcare professionals with experience working with people with SMHDs and concurrent kidney disease. Interview data were analysed and interpreted using reflexive thematic analysis. Results: Four themes were generated from the data: 1. "It's about understanding their limitations and challenges, without limiting their rights" describes how some people with SMHDs need additional support when accessing kidney care due to challenges with their mental state, motivation, cognitive difficulties, or mistrust of the healthcare system. 2. "There are people falling through the cracks" describes how the separation of physical and mental healthcare, combined with under-resourcing and understaffing, results in poorer outcomes for people with SMHDs. 3. "Psychiatry is a black spot in our continuing medical education" describes how many renal healthcare providers have limited confidence in their understanding of mental health and their ability to provide care for people with SMHDs. 4. "When they present to a busy emergency department with a problem, the staff tend to go '…psych patient"" describes how stigma towards people with SMHDs can negatively impact quality of care. Conclusion: Healthcare professionals accounts' describe how people with SMHDs and kidney disease can have favourable outcomes if they have appropriate hospital, community and social supports. Findings indicate that effective management of kidney disease for people with SMHDs requires integrated physical and mental health care, which takes an individualised "whole person" approach to addressing the interaction between kidney disease and mental health.

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.

Pre-eclampsia is associated with complement pathway activation in the maternal and fetal circulation, and placental tissue.

OBJECTIVES: Pre-eclampsia (PE) is a leading cause of obstetric morbidity, with no definitive therapy other than delivery. We aimed to compare complement markers in maternal and fetal circulation, and placental tissue, between women with PE and healthy pregnant controls. STUDY DESIGN: Maternal and umbilical cord blood was tested for iC3b, C3, C4, properdin, Ba and C5b-9, and placental tissue for C3d, C4d, C9 and C1q, from women with PE (n = 34) and healthy pregnant controls (n = 33). Maternal properdin and Ba tests were repeated in a separate validation cohort (PE n = 35; healthy pregnant controls n = 35). MAIN OUTCOME MEASURES: Complement concentrations in maternal and umbilical cord blood, and placental immunohistochemical complement deposition. RESULTS: Women with PE had significantly lower concentrations of properdin (mean: 4828 vs 6877 ng/ml, p < 0.001) and C4 (mean: 0.20 vs 0.31 g/l, p < 0.001), and higher Ba (median: 150 vs 113 ng/ml, p = 0.012), compared to controls. After controlling for gestational age at blood draw, average properdin concentration was 1945 ng/ml lower in PE vs controls (95 % CI: 1487-2402, p < 0.001). Of the cord blood markers assessed, only Ba differed significantly between PE and controls (median: 337 vs 233 ng/ml, p = 0.004). C4d staining of the syncytiotrophoblast membrane was increased in PE vs controls (median immunoreactivity score 3 vs 0, p < 0.001). Maternal properdin and C4 were significantly negatively correlated with placental C4d staining. CONCLUSIONS: Our data confirm excessive placental complement deposition associated with significant concurrent changes in maternal and fetal circulating complement biomarkers in PE. Inhibition of complement activation is a potential therapeutic target.

Chronic kidney disease and severe mental illness: a scoping review.

BACKGROUND: People who have severe mental illness experience higher rates of long-term conditions and die on average 15-20 years earlier than people who do not have severe mental illness, a phenomenon known as the mortality gap. Long-term conditions, such as diabetes, impact health outcomes for people who have severe mental illness, however there is limited recognition of the relationship between chronic kidney disease and severe mental illness. Therefore, the aim of this scoping review was to explore the available evidence on the relationship between chronic kidney disease and severe mental illness. METHODS: Electronic databases, including MEDLINE, Embase, CINAHL, and PsycINFO were searched. The database searches were limited to articles published between January 2000-January 2022, due to significant progress that has been made in the detection, diagnosis and treatment of both SMI and CKD. Articles were eligible for inclusion if they explored the relationship between SMI and CKD (Stages 1-5) in terms of prevalence, risk factors, clinical outcomes, and access to treatment and services. Severe mental illness was defined as conditions that can present with psychosis, including schizophrenia, schizoaffective disorder, bipolar disorder, and other psychotic disorders. Thirty articles were included in the review. RESULTS: The included studies illustrated that there is an increased risk of chronic kidney disease amongst people who have severe mental illness, compared to those who do not. However, people who have severe mental illness and chronic kidney disease are less likely to receive specialist nephrology care, are less likely to be evaluated for a transplant, and have higher rates of mortality. CONCLUSION: In conclusion, there is a dearth of literature in this area, but the available literature suggests there are significant health inequalities in kidney care amongst people who have severe mental illness. Further research is needed to understand the factors that contribute to this relationship, and to develop strategies to improve both clinical outcomes and access to kidney care.

Exploring biopsychosocial correlates of pregnancy risk and pregnancy intention in women with chronic kidney disease.

INTRODUCTION: Women with Chronic Kidney Disease (CKD) are at increased risk of adverse pregnancy and renal outcomes. It is unknown how women with CKD understand their pregnancy risk. This nine-centre, cross-sectional study aimed to explore how women with CKD perceive their pregnancy risk and its impact on pregnancy intention, and identify associations between biopsychosocial factors and perception of pregnancy risk and intention. METHODS: Women with CKD in the UK completed an online survey measuring their pregnancy preferences; perceived CKD severity; perception of pregnancy risk; pregnancy intention; distress; social support; illness perceptions and quality of life. Clinical data were extracted from local databases. Multivariable regression analyses were performed. Trial registration: NCT04370769. RESULTS: Three hundred fifteen women participated, with a median estimated glomerular filtration rate (eGFR) of 64 ml/min/1.73m2 (IQR 56). Pregnancy was important or very important in 234 (74%) women. Only 108 (34%) had attended pre-pregnancy counselling. After adjustment, there was no association between clinical characteristics and women's perceived pregnancy risk nor pregnancy intention. Women's perceived severity of their CKD and attending pre-pregnancy counselling were independent predictors of perceived pregnancy risk. Importance of pregnancy was an independent predictor of pregnancy intention but there was no correlation between perceived pregnancy risk and pregnancy intention (r = - 0.002, 95% CI - 0.12 to 0.11). DISCUSSION: Known clinical predictors of pregnancy risk for women with CKD were not associated with women's perceived pregnancy risk nor pregnancy intention. Importance of pregnancy in women with CKD is high, and influences pregnancy intention, whereas perception of pregnancy risk does not.