Compromised kidney function is associated with an array of environmental contaminants and pathogens that may be considered for regulation. However, there are few valuation estimates for kidney effects for use in benefit–cost analyses, particularly willingness-to-pay estimates. This paper is one of several surveys valuing morbidity developed by the OECD Surveys to elicit Willingness-to-pay to Avoid Chemicals-related negative Health Effects project, which aims to improve the basis for benefit–cost analyses. We report the results of a stated preference survey valuing reduced the risk of symptomatic chronic kidney disease, filling an important gap in the valuation literature and addressing a need for applied benefits analysis of chemical regulation. The survey was administered to representative samples in each of 10 countries: Canada, Chile, China, Denmark, Germany, Italy, Norway, Türkiye, the United Kingdom, and the United States. The mean (median) WTP for an average reduction of 3.5 in 1,000 of the risk of serious kidney disease over 5 years is $2,609 ($764), corresponding to a mean (median) value per statistical case (VSC) of chronic kidney disease of $805,000 ($224,000). The mean VSC varies between $700,000 for Canada and $1,200,000 for Türkiye.

Adherence to a Mediterranean lifestyle may be a useful primary and secondary prevention strategy for chronic kidney disease (CKD). This cross-sectional study aimed to explore adherence to a Mediterranean lifestyle and its association with cardiometabolic markers and kidney function in 99 people aged 73⋅2 ± 10⋅5 years with non-dialysis dependant CKD (stages 3–5) at a single Australian centre. Adherence was assessed using an a priori index, the Mediterranean Lifestyle (MEDLIFE) index. Cardiometabolic markers (total cholesterol, LDL-cholesterol, HbA1c and random blood glucose) and kidney function (estimated GFR) were sourced from medical records and blood pressure measured upon recruitment. Overall, adherence to a Mediterranean lifestyle was moderate to low with an average MEDLIFE index score of 11⋅33 ± 3⋅31. Adherence to a Mediterranean lifestyle was associated with employment (r 0⋅30, P = 0⋅004). Mediterranean dietary habits were associated with cardiometabolic markers, such as limiting sugar in beverages was associated with lower diastolic blood pressure (r 0⋅32, P = 0⋅002), eating in moderation with favourable random blood glucose (r 0⋅21, P = 0⋅043), having more than two snack foods per week with HbA1c (r 0⋅29, P = 0⋅037) and LDL-cholesterol (r 0⋅41, P = 0⋅002). Interestingly, eating in company was associated with a lower frequency of depression (χ2 5⋅975, P = 0⋅015). To conclude, Mediterranean dietary habits were favourably associated with cardiometabolic markers and management of some comorbidities in this group of people with non-dialysis dependent CKD.

Preterm birth (delivery <37 weeks of gestation) is associated with impaired glomerular capillary growth in neonates; if this persists, it may be a contributing factor in the increased risk of hypertension and chronic kidney disease in people born preterm. Therefore, in this study, we aimed to determine the long-term impact of preterm birth on renal morphology, in adult sheep. Singleton male sheep were delivered moderately preterm at 132 days (~0.9) of gestation (n = 6) or at term (147 days gestation; n = 6) and euthanised at 14.5 months of age (early adulthood). Stereological methods were used to determine mean renal corpuscle and glomerular volumes, and glomerular capillary length and surface area, in the outer, mid and inner regions of the renal cortex. Glomerulosclerosis and interstitial collagen levels were assessed histologically. By 14.5 months of age, there was no difference between the term and preterm sheep in body or kidney weight. Renal corpuscle volume was significantly larger in the preterm sheep than the term sheep, with the preterm sheep exhibiting enlarged Bowman’s spaces; however, there was no difference in glomerular volume between groups, with no impact of preterm birth on capillary length or surface area per glomerulus. There was also no difference in interstitial collagen levels or glomerulosclerosis index between groups. Findings suggest that moderate preterm birth does not adversely affect glomerular structure in early adulthood. The enlarged Bowman’s space in the renal corpuscles of the preterm sheep kidneys, however, is of concern and merits further research into its cause and functional consequences.

Introduction: Very low concentrations of high-sensitivity cardiac troponin can rule-out myocardial infarction (MI) at ED arrival in patients with chest pain. However, this single troponin rule-out strategy works poorly in patients with renal impairment and elevated baseline troponin levels. The objective of this study was to develop and validate a troponin adjustment strategy to accurately rule-out MI with a single hs-cTnTmeasurement in patients with kidney dysfunction. Methods: We used data from three cohorts of ED chest pain patients to develop an adjustment score for a high-sensitivity troponin T (hs-cTnT) assay in patients with kidney dysfunction. The derivation cohort (n = 8846) used administrative and registry data. Two validation cohorts (n = 1187 and 1092) were prospectively-collected. The score assigned points for increasing hs-cTnT levels and subtracted points for lower estimated glomerular filtration rate (eGFR). In the derivation cohort, hs-cTnT concentrations achieving 98.5% sensitivity in of patients with eGFR ≥60, 45-59, 30-44, 15-29 and <15 were assigned ascending positive integer values. Negative integer values were assigned to eGFR values 45-59, 30-44, 15-29 and <15. The scpres for troponin and eGFR were summed for each patient, with scores ranging from −4 to +5. The proportion of patients with 7-day MI ruled out by a score ≤0, sensitivity, NPV, negative likelihood ratio (LR-) and area under the curve (AUC) were quantified in each study cohort. Results: The derivation and validation cohorts had 7-day MI rates of 5.7, 8.6 and 9.1%. In the derivation cohort, a score ≤0 ruled out MI in 35% of patients, with a sensitivity for 7-day MI of 99.5% (95% CI 98-100), NPV of 99.9% (95% CI 98.4-99.9), LR- of 0.02 (95% CI 0.01-0.05) and AUC of 0.88. In the first validation cohort, a score ≤0 ruled out MI in 45% of patients, with a sensitivity for 7-day MI of 97% (95% CI 90-100%), NPV of 99% (95% CI 98-100%), LR- 0.06 (0.02-0.18) and AUC of 0.89. In the second validation cohort, a score ≤0 ruled out MI in 20% of patients, with a sensitivity for 7-day MI of 96% (95% CI 93-99%), NPV of 98% (95% CI 96-100%), LR- of 0.16 (95% CI 0.07-0.39) and AUC of 0.78. Conclusion: We developed and validated a simple scoring system to adjust hs-cTnT concentrations for a patient's kidney function that enables MI to be ruled out in a large proportion of chest pain patients using a single measurement on ED presentation.

Renal disease has a high incidence in cats, and some evidence implicates dietary P as well. To investigate this further, two studies in healthy adult cats were conducted. Study 1 (36 weeks) included forty-eight cats, stratified to control or test diets providing 1·2 or 4·8 g/1000 kcal (4184 kJ) P (0 or approximately 3·6 g/1000 kcal (4184 kJ) inorganic P, Ca:P 1·2, 0·6). Study 2 (29 weeks) included fifty cats, stratified to control or test diets, providing 1·3 or 3·6 g/1000 kcal (4184 kJ) P (0 or approximately 1·5 g/1000 kcal (4184 kJ) inorganic P, Ca:P 1·2, 0·9). Health markers, glomerular filtration rate (GFR) and mineral balance were measured regularly, with abdominal ultrasound. Study 1 was halted after 4 weeks as the test group GFR reduced by 0·4 (95 % CI 0·3, 0·5) ml/min per kg, and ultrasound revealed changes in renal echogenicity. In study 2, at week 28, no change in mean GFR was observed (P >0·05); however, altered renal echogenicity was detected in 36 % of test cats. In agreement with previous studies, feeding a diet with Ca:P <1·0, a high total and inorganic P inclusion resulted in loss of renal function and changes in echogenicity suggestive of renal pathology. Feeding a diet containing lower total and inorganic P with Ca:P close to 1·0 led to more subtle structural changes in a third of test cats; however, nephrolithiasis occurred in both diet groups, complicating data interpretation. We conclude that the no observed adverse effects level for total dietary P in adult cats is lower than 3·6 g/1000 kcal (4184 kJ), however the effect of inorganic P sources and Ca:P require further investigation.

Evidence from animal models indicates that exposure to an obesogenic or hyperglycemic intrauterine environment adversely impacts offspring kidney development and renal function. However, evidence from human studies has not been evaluated systematically. Therefore, the aim of this systematic review was to synthesize current research in humans that has examined the relationship between gestational obesity and/or diabetes and offspring kidney structure and function. Systematic electronic database searches were conducted of five relevant databases (CINAHL, Cochrane, EMBASE, MEDLINE and Scopus). Preferred Reporting Items for Systematic Reviews and Meta-analysis guidelines were followed, and articles screened by two independent reviewers generated nine eligible papers for inclusion. Six studies were assessed as being of ‘neutral’ quality, two of ‘negative’ and one ‘positive’ quality. Observational studies suggest that offspring exposed to a hyperglycemic intrauterine environment are more likely to display markers of renal dysfunction and are at higher risk of end-stage renal disease. There was limited and inconsistent evidence for a link between exposure to an obesogenic intrauterine environment and offspring renal outcomes. Offspring renal outcome measures across studies were diverse, with a large variation in offspring age at follow-up, limiting comparability across studies. The collective current body of evidence suggests that intrauterine exposure to maternal obesity and/or diabetes adversely impacts renal programming in offspring, with an increased risk of kidney disease in adulthood. Further high-quality, longitudinal, prospective cohort studies that measure indicators of offspring renal development and function, including fetal kidney volume and albuminuria, at standardized follow-up time points, are warranted.

Introduction: Patients with chronic kidney disease (CKD) are at high risk of cardiovascular events, and have worse outcomes following acute myocardial infarction (AMI). Cardiac troponin is often elevated in CKD, making the diagnosis of AMI challenging in this population. We sought to quantify test characteristics for AMI of a high-sensitivity troponin T (hsTnT) assay performed at emergency department (ED) arrival in CKD patients with chest pain, and to derive rule-out cutoffs specific to patient subgroups stratified by estimated glomerular filtration rate (eGFR). We also quantified the sensitivity and classification performance of the assays limit of detection (5 ng/L) and the FDA-approved limit of quantitation (6 ng/L) for ruling out AMI at ED arrival. Methods: Consecutive patients in four urban EDs from the 2013 calendar year with suspected cardiac chest pain who had a Roche Elecsys hsTnT assay performed on arrival were included f. This analysis was restricted to patients with an eGFR< 60 ml/min/1.73m2. The primary outcome was 7-day AMI. Secondary outcomes included major adverse cardiac events (death, AMI and revascularization). Test characteristics were calculated and ROC curves were generated for eGFR subgroups. Results: 1416 patients were included. 7-day AMI incidence was 10.1%. 73% of patients had an initial hsTnT concentration greater than the assays 99th percentile (14 ng/L). TCurrently accepted cutoffs to rule out MI at ED arrival ( 5 ng/L and 6 ng/L) had 100% sensitivity for AMI, but no patients with an eGFR less than 30 ml/min/1.73M had hsTnT concentrations below these thresholds. We derived eGFR-adjusted cutoffs to rule out MI with sensitivity >98% at ED arrival, which were able to rule out 6-42% of patients, depending on eGFR category. The proportion of patients able to be accurately ruled-in with a single hsTnT assay was substantially lower among patients with an eGFR <30 ml/min/1.73m2 (6-20% vs 25-43%). We also derived eGFR-adjusted cutoffs to rule-in AMI with specificity >90%, which accurately ruled-in up to 18% of patients. Conclusion: Cutoffs achieving acceptable diagnostic performance for AMI using single hsTnT sampling on ED arrival may have limited clinical utility, particularly among patients with very low eGFR. The ideal diagnostic strategy for AMI in patients with CKD likely involves serial high-sensitivity troponin testing with diagnostic thresholds customized to different eGFR categories.

Kidney diseases are the ninth leading cause of death in the USA. In these patients cardiovascular mortality is greater than in the general population. This observation, not completely explained by the so-called ‘traditional’ cardiovascular risk factors, lead the authors to postulate other ‘emerging’ ones found in chronic renal failure patients. Among these new findings, nutritional status, considered as the balance existing between nutrient requirements and intakes, plays an important role for the development of cardiovascular diseases. In fact several nutritional parameters are widely known as pathophysiological determinants of cardiovascular disturbances, which are based on accelerated atherosclerosis, due especially to enhanced oxidative stress and endothelial dysfunction. Chronic renal failure is a clinical condition that from many points of view seems to be a chronic inflammatory state, and many studies confirm this observation. This influences nutritional status especially in dialysis patients. Malnutrition is related in turn to accelerated atherosclerosis thus leading to a postulated ‘malnutrition, inflammation, atherosclerosis’ (MIA) syndrome in which malnutrition, inflammation and atherosclerosis contribute to an elevated cardiovascular mortality rate. The present review explores this issue, first by describing epidemiological aspects of malnutrition in chronic renal failure patients and then by analysing the specific biochemical and metabolic features of these patients.

Dietary soya protein substitution for casein initiated at weaning slows disease progression in animal models of chronic renal disease. As there is increasing evidence that fetal programming can have a significant impact on kidney physiology and function in offspring, the objective of the current study was to determine whether exposure to soya protein in the diet earlier than weaning would have further benefits. Han:SPRD-cy (cy/+) breeder rats were fed a casein-based or soya protein-based diet 2 weeks prior to mating, throughout pregnancy and during lactation. Following this maternal period, 3-week-old pups were given either the same or the alternate diet for a 7-week weaning period. Dietary soya protein compared with casein in the maternal or weaning period both independently resulted in less renal inflammation (macrophage infiltration lower by 24 % (P = 0·0003) and 32 % (P < 0·0001), respectively). When soya protein was given in both feeding periods, the effect was additive. Soya protein substitution for casein resulted in less oxidative damage as indicated by 28 % lower oxidized-LDL staining (P = 0·013) when present in the maternal period, or in the weaning period (by 56 %, P < 0·0001). Renal cell proliferation was reduced by 29–33 % (P < 0·05) in rats given soya protein whether the exposure was during the maternal or weaning period. Soya protein compared with casein in the maternal period also resulted in 33 % (P = 0·0013) less proteinuria, indicating superior renal function. Dietary soya protein during pregnancy and lactation represents a potential preventative approach in treating for those with congenital kidney diseases.

The primary hyperoxalurias type 1 (PH1) and type 2 (PH2) are autosomal recessive calcium oxalate kidney stone diseases caused by deficiencies of the metabolic enzymes alanine:glyoxylate aminotransferase (AGT) and glyoxylate/hydroxypyruvate reductase (GR/HPR), respectively. Over 50 mutations have been identified in the AGXT gene (encoding AGT) in PH1, associated with a wide variety of effects on AGT, including loss of catalytic activity, aggregation, accelerated degradation, and peroxisome-to-mitochondrion mistargeting. Some of these mutations segregate and interact synergistically with a common polymorphism. Over a dozen mutations have been found in the GRHPR gene (encoding GR/HPR) in PH2, all associated with complete loss of glyoxylate reductase enzyme activity and immunoreactive protein. The crystal structure of human AGT, but not human GR/HPR, has been solved, allowing the effects of many of the mutations in PH1 to be rationalised in structural terms. Detailed analysis of the molecular aetiology of PH1 and PH2 has led to significant improvements in all aspects of their clinical management. Enzyme replacement therapy by liver transplantation can provide a metabolic cure for PH1, but it has yet to be tried for PH2. New treatments that aim to counter the effects of specific mutations on the properties of the enzymes could be feasible in the not-too-distant future.