BACKGROUND:Clinicians caring for kidney transplant recipients (KTRs) most commonly use estimated glomerular filtration rate (eGFR) to guide medication dosing as it is the most readily available measure of kidney function. Which eGFR equations provide the most accurate medication dosing guidance for KTRs remains uncertain. METHODS:We studied 415 stable KTRs in Canada and New Zealand. Participants completed same-day measurements of creatinine and cystatin C and measured GFR (diethylenetriaminepentaacetic acid). Chronic Kidney Disease Epidemiology Collaboration, European Kidney Function Consortium, and transplant-specific eGFR equations were compared with both Cockcroft-Gault creatinine clearance (CrCl) and measured GFR. eGFR equations were assessed both indexed to a standardized body surface area (BSA) of 1.73 m 2 (milliliter per minute per 1.73 m 2 , as is conventional reporting from most clinical laboratories) and nonindexed (milliliter per minute) accounting for actual BSA. The primary outcome was the proportion of medication dosing discordance relative to Cockcroft-Gault CrCl or measured GFR for 8 commonly prescribed medications. Stratified analyses were performed on the basis of obesity status. RESULTS:Nonindexed eGFR equations (milliliter per minute) resulted in substantially lower medication dosing discordance compared with indexed eGFR equations (milliliter per minute per 1.73 m 2 ). These findings were most pronounced among KTRs with obesity, in whom underdosing was frequent. When compared with Cockcroft-Gault CrCl, the lowest proportion of discordance was found with the nonindexed 2023 transplant-specific equation. When compared with measured GFR, the lowest proportion of discordance was found with the nonindexed 2021 Chronic Kidney Disease Epidemiology Collaboration Cr/CysC equation. CONCLUSIONS:Nonindexed eGFR values accounting for actual BSA should be used by clinicians for medication dosing in KTRs. These findings may inform KT providers about which eGFR equations provide the safest, most accurate medication dosing guidance for KTRs.

BACKGROUND:Social determinants of health are non-medical factors that impact health. For patients with chronic kidney disease (CKD) progressing to kidney failure, the influence of social determinants of health on dialysis modality selection (haemodialysis vs. peritoneal dialysis (PD)) is incompletely understood. METHODS:Retrospective cohort study of 981 consecutive patients with advanced CKD referred to the Ottawa Hospital Multi-Care Kidney Clinic (Canada) who progressed to dialysis from 2010 to 2021. Multivariable logistic regression was used to measure odds ratios (OR) for the associations between social determinants of health (education, employment, marital status and residence) and modality of dialysis initiation. RESULTS:The mean age and estimated glomerular filtration rate were 64 and 18 mL/min/1.73 m2, respectively. Not having a high school degree was associated with lower odds of initiating dialysis via PD compared to having a college degree (29% vs. 48%, OR 0.55 (95% confidence interval (CI) 0.34-0.88)). Unemployment was associated with lower odds of initiating dialysis via PD compared to active employment (38% vs. 62%, OR 0.40 (95% CI 0.27-0.60)). Being single was associated with lower odds of initiating dialysis via PD compared to being married (35% vs. 48%, adjusted OR 0.52 (95% CI 0.39-0.70)). Living alone at home was associated with lower odds of initiating dialysis via PD compared to living at home with family (33% vs. 47%, adjusted OR 0.55 (95% CI 0.39-0.78)). CONCLUSIONS:Social determinants of health including education, employment, marital status and residence are associated with dialysis modality selection. Addressing these 'upstream' social factors may allow for more equitable outcomes during the transition from advanced CKD to kidney failure.

Background The transition from chronic kidney disease (CKD) to kidney failure is a vulnerable time for patients, with suboptimal transitions associated with increased morbidity and mortality. Whether social determinants of health are associated with suboptimal transitions is not well understood. Methods This retrospective cohort study included 1070 patients with advanced CKD who were referred to the Ottawa Hospital Multi-Care Kidney Clinic and developed kidney failure (dialysis or kidney transplantation) between 2010 and 2021. Social determinant information, including education level, employment status and marital status, was collected under routine clinic protocol. Outcomes surrounding suboptimal transition included inpatient (versus outpatient) dialysis starts, pre-emptive (versus delayed) access creation and pre-emptive kidney transplantation. We examined the association between social determinants of health and suboptimal transition outcomes using multivariable logistic regression. Results The mean age and estimated glomerular filtration rate were 63 years and 18 ml/min/1.73 m(2), respectively. Not having a high school degree was associated with higher odds for an inpatient dialysis start compared with having a college degree {odds ratio [OR] 1.71 [95% confidence interval (CI) 1.09-2.69]}. Unemployment was associated with higher odds for an inpatient dialysis start [OR 1.85 (95% CI 1.18-2.92)], lower odds for pre-emptive access creation [OR 0.53 (95% CI 0.34-0.82)] and lower odds for pre-emptive kidney transplantation [OR 0.48 (95% CI 0.24-0.96)] compared with active employment. Being single was associated with higher odds for an inpatient dialysis start [OR 1.44 (95% CI 1.07-1.93)] and lower odds for pre-emptive access creation [OR 0.67 (95% CI 0.50-0.89)] compared with being married. Conclusions Social determinants of health, including education, employment and marital status, are associated with suboptimal transitions from CKD to kidney failure.

Context Dietary consumption of phosphate is increasing, and elevated serum phosphate is associated with increased cardiovascular disease (CVD) risk. Sex differences in phosphate homeostasis and response to changes in dietary phosphate intake, which are not captured by clinically measured analytes, may contribute to differences in CVD presentation and bone disease. Objective To assess sex differences in acute phosphate homeostasis in response to a single oral phosphate challenge. Design Cross-sectional. Setting General community. Participants 78 participants (40-76 years) with measured glomerular filtration rate >60 mL/min/1.73 m(2) and no clinically diagnosed CVD and 14 young healthy adults. Main Outcome Measures To elucidate subtle alterations in phosphate homeostasis, we employ an acute challenge whereby the hormonal response, circulating mineral levels, and urinary excretion are assessed following an oral challenge of phosphate. Results Although both males and females had similar changes in circulating phosphate, calcium, and parathyroid hormone in response to the challenge, females excreted similar to 1.9x more phosphate and similar to 2.7x more calcium than males, despite not consuming calcium. These sex differences were recapitulated in healthy young adults. This excretion response did not correlate to age, serum phosphate, or estradiol levels. The females with greater excretion of phosphate had higher levels of bone resorption markers compared to formation markers. Conclusions Taken together, these data identify sex differences in acute phosphate homeostasis, specifically that females may mobilize and excrete endogenous sources of calcium and phosphate in response to oral phosphate compared to males. While high levels of dietary phosphate negatively impact bone, our results suggest that females may incur more risk from these diets.

Peer review aims to select articles for publication and to improve articles before publication. We believe that this process can be infused by kindness without losing rigor. In 2014, the founding editorial team of the Canadian Journal of Kidney Health and Disease (CJKHD) made an explicit commitment to treat authors as we would wish to be treated ourselves. This broader group of authors reaffirms this principle, for which we suggest the terminology "supportive review."

Rationale & Objective: The Kidney Failure Risk Equation (KFRE) is widely used to predict the risk of kidney replacement therapy (KRT) initiation in chronic kidney disease (CKD) stages G3-G5. The new Grams calculator developed for advanced CKD (stage G4+) predicts KRT initiation, cardiovascular events, and death by uniquely incorporating the competing risk of death. We aimed to validate this tool in a stage G4+ cohort for death and KRT. Study Design: Retrospective cohort study. Setting & Participants: 442 patients with CKD stage G4+ (mean +/- SD age, 73 +/- 12 years; mean +/- SD estimated glomerular filtration rate, 20 +/- 6.2 mL/min/1.73 m(2)) who visited the multidisciplinary CKD clinic at Kingston Health Sciences Center in Ontario, Canada. Outcomes & Analytical Approach: Discrimination and calibration were examined for the outcome of death using the 2- and 4-year Grams scores. The 2- and 5-year KFRE and 2- and 4-year Grams scores were compared in terms of discrimination and calibration for KRT. Results: There were 91, 161, and 206 death events and 90, 145, and 159 KRT events in our cohort at 2, 4, and 5 years, respectively. The Grams model demonstrated modest discrimination for death at 4 years (area under the curve [AUC] 0.70; 95% CI, 0.65-0.75) and performed worse at 2 years (AUC, 0.63; 95% CI, 0.57-0.70). It only overpredicted death by approximately 10% across most of the predicted range. Both models had similar discrimination for KRT at 2 years (KFRE AUC, 0.83; 95% CI, 0.78-0.88 and Grams AUC, 0.8; 95% CI, 0.76-0.87), 4 years (Grams AUC, 0.82; 95% CI, 0.77-0.86), and 5 years (KFRE AUC, 0.81; 95% CI, 0.76-0.85). There was excellent calibration for KRT using the 2-year KFRE and Grams values for predicted risk thresholds of <= 15% and using the 5-year KFRE and 4-year Grams values for predicted risk thresholds of <= 20%. At higher risk ranges, KFRE overpredicts and Grams underpredicts the KRT risk. Limitations: This is a single-center study with a primarily White cohort limited by smaller sample sizes at the higher ranges of the predicted risks, particularly for the Grams calculator. Conclusions: The Grams model provides moderately accurate death predictions, and consideration should be given to its incorporation into patient education and advanced care planning. Both the Grams and KFRE models remain clinically useful for determining KRT risks in advanced CKD.

Abstract Introduction Glomerular filtration rate (GFR) is measured from the late plasma disappearance curve of an exogenous tracer, after correction for the early decay – corresponding to the distribution of the tracer – using various equations. These equations display the highest discrepancies in the GFR range above 90 ml/min/1.73m2, and their respective performances against a reference, urinary GFR measurement are unclear. Methods In patients with mGFR \u003e90 ml/min/1.73m2 from six different cohorts, we compared GFR obtained from the plasma clearance of iohexol or 51Cr-EDTA, after correction using Chantler (C), Brochner-Mortensen (BM), Fleming (F), Jodal-Brochner-Mortensen (JBM), and Ng (N) equations, with urinary clearance of the same tracers or inulin. Results In 438 participants (median age 41 [ 39;42] years, 43% women), median urinary clearance was 100.8 [94.7;112.6] mL/min/1.73m2. Plasma clearances using the correction equations were 105.7 [96.8;119.2], 102.4 [95.2;112.9], 100.7 [93.6;111.1], 102.6 [95.2;113.4], and 106.0 [98.2;117.6] mL/min/1.73m2, for C, BM, F, JBM, and N, respectively. Concordance correlation coefficients between plasma and urinary clearances were poor for all equations. Compared to urinary clearances, BM, F, and JBM displayed the best accuracy within 10% (73, 72 and 71% respectively, versus 63 and 66% for C and N), while BM and JBM had the lowest median biases. Accuracy of all equations was especially low in the hyperfiltration range (urinary clearance \u003e130 ml/min/1.73m2). Conclusion The BM and JBM equations displayed the best overall performances to correct for the early disappearance curve. Results of these equations should be interpreted with caution, especially in the highest GFR range.

Introduction: Glomerular filtration rate (GFR) is measured from the late plasma disappearance curve of an exogenous tracer, after correction for the early decay—corresponding to the distribution of the tracer—using various equations. These equations display the highest discrepancies in the GFR range above 90 ml/min per 1.73 m2, and their respective performances against a reference, urinary GFR measurement are unclear. Methods: In patients with mGFR >90 ml/min per 1.73 m2 from 6 different cohorts, we compared GFR obtained from the plasma clearance of iohexol or 51Cr-ethylenediamine tetraacetic acid (EDTA), after correction using Chantler (C), Bröchner-Mortensen (BM), Fleming (F), Jodal-Bröchner-Mortensen (JBM), and Ng (N) equations, with urinary clearance of the same tracers or inulin. Results: In 438 participants (median age 41 [39–42] years, 43% women), the median urinary clearance was 100.8 (94.7–112.6) ml/min per 1.73 m2. Plasma clearances using the correction equations were 105.7 (96.8–119.2), 102.4 (95.2–112.9), 100.7 (93.6–111.1), 102.6 (95.2–113.4), and 106.0 (98.2–117.6) ml/min per 1.73 m2 for C, BM, F, JBM, and N, respectively. Concordance correlation coefficients between plasma and urinary clearances were poor for all equations. Compared with urinary clearances, BM, F, and JBM displayed the best accuracy within 10% (73%, 72%, and 71%, respectively, vs. 63% and 66% for C and N), whereas BM and JBM had the lowest median biases. Accuracy of all equations was especially low in the hyperfiltration range (urinary clearance >130 ml/min per 1.73 m2). Conclusion: The BM and JBM equations displayed the best overall performances to correct for the early disappearance curve. Results of these equations should be interpreted with caution, especially in the highest GFR range.

Stable carbon and nitrogen isotope compositions were determined for camelid bone collagen, hair, and wool (fibre) sampled from textiles from archaeological sites in the Santa Valley (north coast of Peru) occupied during Moche III (El Castillo, A.D. 300-500) and Moche IV (Guadalupito, A.D. 500-700) phases; a small number of camelid bone collagen samples were also analysed from the Late Suchimancillo Phase (A.D. 0-300). These data suggest that localised camelid husbandry was practiced in the Santa Valley from at least the Moche III phase. The nature of camelid husbandry likely involved animals being kept spatially segregated and fed a diverse range of fodder. The isotopic compositions of the bone collagen and wool textiles were very similar, which suggests that the wool that was used to produce the textiles was derived from local camelids rather than being acquired from the highlands. The transition from Moche III to Moche IV, which saw a significant increase in Mochica presence in the Santa Valley, was not accompanied by major changes in camelid husbandry practices. Localised camelid husbandry continued through this transition with minimal change; the prolonged droughts of the sixth century A.D. had no discernable effect on camelid husbandry, probably due to the special hydraulic conditions unique to the Santa Valley.

There are disparities in the diagnosis, treatment and prognosis for cardiovascular disease (CVD) between sexes and these differences are rooted, in part, in biology. Abnormalities in phosphate regulation and vascular calcification are important risk factors for CVD, even in the setting of preserved kidney function. Elevations of serum phosphate within the normal range are a risk factor for CVD. Abnormalities and differences in phosphate regulation are often not reflected in single circulating measurements of serum phosphate, but can be revealed by the acute circulating and mineral response to an oral phosphate challenge. The aim of this study was to assess the differences between sexes in the hormonal response and excretion capacity of an oral phosphate challenge. Healthy people (N=78) free of type 2 diabetes (T2D) and symptomatic CVD (∼10 males and ∼10 females from each decade between 40 and 80 years) were recruited from Kingston, Ontario, Canada. Following a 12-hour fast, participants consumed a 1250 mg phosphate drink (sodium phosphate) where blood and urine were collected hourly from baseline to 4 hours following the oral challenge. In the cohort, 43 of the participants were female and the average age for males and females was 58.4±10.8 and 60.0±9.6, respectively. Kidney function was normal, with eGFR measurements of 88±12ml/min/1.73m2 and 93±14ml/min/1.73m2, in males and females respectively. There was no difference in fasting baseline levels of phosphaturic hormones, fibroblast growth factor 23 (FGF-23) or parathyroid hormone (PTH) between sexes, nor was there an impact of age on either of these measures. Females had a similar fasted urinary phosphate-to-creatinine ratio as males, but higher circulating serum phosphate (1.2±0.1 mM v 1.0±0.1 mM, p<0.01). In response to the phosphate challenge, females increased their phosphate excretion more than males, significant for all measured time points (Figure 1A). There was a substantial increase in urinary excretion of calcium in females only (Figure 1B). Circulating calcium was not altered by the challenge nor different between the sexes. After adjustment for sex and age, testosterone was inversely correlated with fasted serum phosphate (r=-0.20) and urinary phosphate-to-creatinine ratio (r=-0.28), but not to measures of acute response to the oral challenge. Estradiol was not correlated to any measure of phosphate homeostasis, but correlated negatively to serum calcium (r=-0.30) and positively with post-challenge urinary calcium excretion (r=0.22), after adjustment for age and sex. Females have greater capacity to excrete a phosphate load than males and also excrete calcium in response to phosphate. Impaired acute phosphate response may lead to increased exposure to circulating phosphate, and in that way may contribute to the initiation or propagation of vascular calcification. Improved acute handling of phosphate may contribute to the lower prevalence of coronary artery calcification and lower risk of developing CVD in females. Phosphate as a stimulus for acute calcium excretion, as well as its correlation to estradiol, has potential importance in relation to dietary phosphate exposure and osteoporosis. These observed differences in mineral homeostasis between females and males may be important as, to date, there has been no attempt to identify sex-specific targets or sex-specific treatment approaches.

In archaeological populations the oxygen isotope composition (6180) of human bones and teeth can be used to reconstruct climatic conditions and landscape mobility by serving as a proxy for changes in delta O-18 of consumed water. Until now, providing this information at the seasonal scale, across broad periods of an individual's life, has been considered impossible because bone remodeling was thought to completely disrupt meaningful patterns preserved in bone microstructure. Recent studies, however, have described large (often > 1 mm) deposits of incremental primary bone persisting well into adulthood, and new technology permits finer scale analysis than ever before. Our objective was to determine the delta O-18 variation across human primary bone layers using high spatial resolution Secondary Ion Mass Spectrometry (SIMS). Results show patterned sinusoidal periodicity, similar to expectations for weather-induced fluctuations in seasonal drinking water. The bone formation rate suggested by the isotopic variation in our study is consistent with other histological assessments of primary lamellar bone formation. The technique thus enables sampling of delta(180) at approximately monthly intervals over more than a decade of bone deposition. Because bone is the most commonly recovered archaeological tissue, applications of this method, even using fragmentary remains, have the potential to enable more detailed reconstructions of political, economic, health, and sociocultural change at life history levels. Future applications may also include identification of remains in historic and forensic contexts and determination of developmental or pathogenic rates in ancient or modern health investigations.

This study investigates the diet of an eleventh century CE parish community located in northwestern Germany. We assessed the isotopic compositions of human ( n = 24) and faunal ( n = 17) bone collagen ( δ 13 C col , δ 15 N col ) and human structural carbonate ( δ 13 C sc ) using skeletal material recovered from the Dalheim cemetery. Traditional interpretation of the isotopic data indicates that Dalheim residents likely relied on a C 3 plant-based diet and consumed some terrestrial animal products without evidence of marine resource input in the diet. Bivariate and multivariate models used as an additional means to assess diet indicate minor consumption of C 4 plant foods in this community. The multivariate-isotope model identified regional similarities and differences in C 4 plant/marine food consumption and in dietary protein sources by comparing data from Dalheim with those of other medieval sites from the published literature. We did not observe sex differences in this population but differences in δ 15 N col suggest that juveniles consumed the lowest trophic level protein.

This study presents sulfur isotope compositions ( δ 34 S) for plants grown in a series of growth chamber and field experiments under controlled conditions. Maize, beans, and squash fertilized with a marine fertilizer (seabird guano) were significantly enriched in 34 S relative to the unfertilized control plants (by +4.0 to +7.2‰) in the growth chamber experiments. No 34 S enrichment was detected in the plants from the field experiment, which likely relates to the recent use of ammonium sulfate fertilizer in these fields and the retention of residual sulfate with a comparatively low δ 34 S. The field experiment provided a basis to estimate the apparent fractionation between soil and plant S associated with uptake and assimilation ( Δ 34 S), which ranged between −4 and −6‰ depending on the taxon and tissue. The use of marine fertilizers has the capacity to increase plant δ 34 S values and complicate quantitative reconstructions of ancient diet based on bulk stable isotope data.

The ancient Maya are known to have relied heavily on maize horticulture. In spite of the fact that maize was responsible for both the ideological and physical survival of the Maya, there was significant variability in the degree to which it was consumed. In this chapter, direct evidence of food consumption provided by the stable isotope composition of carbon and nitrogen is reviewed in terms of variability that existed across time, space, and social variables. Relationships between diet and significant temporal developments such as agricultural intensification, the collapse of Classic Maya society, and the Spanish conquest are examined, along with the use of diet to reconstruct political economies, gender, and status differentiation.

Stable carbon and nitrogen isotopic compositions were determined for wool textiles from the Lambayeque ( c . ad 1100–1320) occupation at Pacatnamú in the Jequetepeque Valley, northern Peru. The isotopic data demonstrate that the wool was not obtained via long‐distance exchange with the highlands and was most probably derived from locally raised camelids. In light of other lines of evidence (diversity of dyes used to produce the same colours in textiles and the low quality of the weaving), textiles at Pacatnamú appear not to have been as effective a marker of political power and prestige for local elites as they were elsewhere in the Andean region.

Background: The international initiative to standardize creatinine (Cr) assays by tracing reference materials to Isotope Dilution Mass Spectrometry (IDMS) assigned values was implemented to reduce interlaboratory variability and improve assay accuracy. Objective: The aims of this study were to examine whether IDMS standardization has improved Cr assay accuracy (bias), interlaboratory variability (precision), total error (TE), and attainment of recommended analytical performance goals. Methods: External Quality Assessment (EQA) data (n = 66 challenge vials) from Ontario, Canada, were analyzed. The bias, precision, TE, and the number of EQA challenge vials meeting performance goals were determined by assay manufacturer before (n = 32) and after (n = 34) IDMS implementation. Results: The challenge vials with the worst bias and precision were spiked with known common interfering substances (glucose and bilirubin). IDMS standardization improved assay bias (10.4%-1.6%, P < .001), but precision remained unchanged (5.0%-4.7%, P = .5) with performance goals not consistently being met. Precision and TE goals based on biologic variation were attained by only 29% to 69% and 32% to 62% of challenge vials. Conclusions: While IDMS standardization has improved Cr assay accuracy and thus reduced TE, significant interlaboratory variability remains. Contemporary Cr assays do not currently meet the standards required to allow for accurate and consistent estimated glomerular filtration rate assessment and chronic kidney disease diagnosis across laboratories. Further improvements in Cr assay performance are needed.