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Abstract In clinical practice, the glomerular filtration rate (GFR), a measurement of kidney functioning, is normally calculated using equations, such as the European Kidney Function Consortium (EKFC) equation. Despite being the most general equation, EKFC, just like previously proposed approaches, can still struggle to achieve satisfactory performance, limiting its clinical applicability. As a possible solution, recently machine learning (ML) has been investigated to improve GFR prediction, nonetheless the literature still lacks a general and multi-center study. Using a dataset with 19,629 patients from 13 cohorts, we investigate if ML can improve GFR prediction in comparison to EKFC. More specifically, we compare diverse ML methods, which were allowed to use age, sex, serum creatinine, cystatin C, height, weight and BMI as features, in internal and external cohorts against EKFC. The results show that the most performing ML method, random forest (RF), and EKFC are very competitive where RF and EKFC achieved respectively P10 and P30 values of 0.45 (95% CI 0.44;0.46) and 0.89 (95% CI 0.88;0.90), whereas EKFC yielded 0.44 (95% CI 0.43; 0.44) and 0.89 (95% CI 0.88; 0.90), considering the entire cohort. Small differences were, however, observed in patients younger than 12 years where RF slightly outperformed EKFC.

Rationale & Objective: Remote patient monitoring (RPM) could improve the quality and efficiency of acute kidney injury (AKI) survivor care. This study described our experience with AKI RPM and characterized its effectiveness. Study Design: A cohort study matched 1:3 to historical controls. Setting & Participants: Patients hospitalized with an episode of AKI who were discharged home and were not treated with dialysis. Exposure: Participation in an AKI RPM program, which included use of a home vital sign and symptom monitoring technology and weekly in-center laboratory assessments. Outcomes: Risk of unplanned hospital readmission or emergency department (ED) visit within 6 months. Analytic Approach: Endpoints were assessed using Cox proportional hazards models. Results: Forty of the 49 patients enrolled in AKI RPM (82%) participated in the program after hospital discharge. Seventy three percent of patients experienced one AKI RPM alert, most commonly related to fluid status. Among those with stage 3 AKI, the risk of unplanned readmission or ED visit within 6 months of discharge was not different between AKI RPM patients (n = 34) and matched controls (n = 102) (HR 1.33 [95% CI, 0.81-2.18]; P = 0.27). The incidence of an ED visit without hospitalization was significantly higher in the AKI RPM group (HR 1.95, [95% CI, 1.05-3.62]; P = 0.035). The risk of an unplanned readmission or ED visit was higher in those with baseline eGFR

Abstract Background There is uncertainty about the long-term risks of living kidney donation. Well-designed studies with controls well-matched on risk factors for kidney disease are needed to understand the attributable risks of kidney donation. Methods The goal of the Minnesota Attributable Risk of Kidney Donation (MARKD) study is to compare the long-term (> 50 years) outcomes of living donors (LDs) to contemporary and geographically similar controls that are well-matched on health status. University of Minnesota (n = 4022; 1st transplant: 1963) and Mayo Clinic LDs (n = 3035; 1st transplant: 1963) will be matched to Rochester Epidemiology Project (REP) controls (approximately 4 controls to 1 donor) on the basis of age, sex, and race/ethnicity. The REP controls are a well-defined population, with detailed medical record data linked between all providers in Olmsted and surrounding counties, that come from the same geographic region and era (early 1960s to present) as the donors. Controls will be carefully selected to have health status acceptable for donation on the index date (date their matched donor donated). Further refinement of the control group will include confirmed kidney health (e.g., normal serum creatinine and/or no proteinuria) and matching (on index date) of body mass index, smoking history, family history of chronic kidney disease, and blood pressure. Outcomes will be ascertained from national registries (National Death Index and United States Renal Data System) and a new survey administered to both donors and controls; the data will be supplemented by prior surveys and medical record review of donors and REP controls. The outcomes to be compared are all-cause mortality, end-stage kidney disease, cardiovascular disease and mortality, estimated glomerular filtration rate (eGFR) trajectory and chronic kidney disease, pregnancy risks, and development of diseases that frequently lead to chronic kidney disease (e.g. hypertension, diabetes, and obesity). We will additionally evaluate whether the risk of donation differs based on baseline characteristics. Discussion Our study will provide a comprehensive assessment of long-term living donor risk to inform candidate living donors, and to inform the follow-up and care of current living donors.

IMPORTANCE:. Meropenem dosing is typically guided by creatinine-based estimated glomerular filtration rate (eGFR), but creatinine is a suboptimal GFR marker in the critically ill. OBJECTIVES:. This study aimed to develop and qualify a population pharmacokinetic model for meropenem in critically ill adults and to determine which eGFR equation based on creatinine, cystatin C, or both biomarkers best improves model performance. DESIGN, SETTING, AND PARTICIPANTS:. This single-center study evaluated adults hospitalized in an ICU who received IV meropenem from 2018 to 2022. Patients were excluded if they had acute kidney injury, were on kidney replacement therapy, or were treated with extracorporeal membrane oxygenation. Two cohorts were used for population pharmacokinetic modeling: a richly sampled development cohort (n = 19) and an opportunistically sampled qualification cohort (n = 32). MAIN OUTCOMES AND MEASURES:. A nonlinear mixed-effects model was developed using parametric methods to estimate meropenem serum concentrations. RESULTS:. The best-fit structural model in the richly sampled development cohort was a two-compartment model with first-order elimination. The final model included time-dependent weight normalized to a 70-kg adult as a covariate for volume of distribution (Vd) and time-dependent eGFR for clearance. Among the eGFR equations evaluated, eGFR based on creatinine and cystatin C expressed in mL/min best-predicted meropenem clearance. The mean (se) Vd in the final model was 18.2 (3.5) liters and clearance was 11.5 (1.3) L/hr. Using the development cohort as the Bayesian prior, the opportunistically sampled cohort demonstrated good accuracy and low bias. CONCLUSIONS AND RELEVANCE:. Contemporary eGFR equations that use both creatinine and cystatin C improved meropenem population pharmacokinetic model performance compared with creatinine-only or cystatin C-only eGFR equations in adult critically ill patients.

Rationale & Objective: Innovative models are needed to address significant gaps in kidney care follow-up for acute kidney injury (AKI) survivors. Study Design: This quasi-experimental pilot study reports the feasibility of the AKI in Care Transitions (ACT) program, a multidisciplinary approach to AKI survivor care based in the primary care setting. Setting & Participants: The study included consenting adults with stage 3 AKI discharged home without dialysis. Interventions: The ACT intervention included predischarge education from nurses and coordinated postdischarge follow-up with a primary care provider and pharmacist within 14 days. ACT was implemented in phases (Usual Care, Education, ACT). Outcomes: The primary outcome was feasibility. Secondary outcomes included process and clinical outcomes. Results: In total, 46 of 110 eligible adults were enrolled. Education occurred in 18/18 and 14/15 participants in the Education and ACT groups, respectively. 30-day urine protein evaluation occurred in 15%, 28%, and 87% of the Usual Care, Education, and ACT groups, respectively (P

Abstract High‐dose methotrexate (HDMTX) pharmacokinetics (PKs), including the best estimated glomerular filtration rate (eGFR) equation that reflects methotrexate (MTX) clearance, requires investigation. This prospective, observational, single‐center study evaluated adult patients with lymphoma treated with HDMTX. Samples were collected at predefined time points up to 96 h postinfusion. MTX and 7‐hydroxy‐MTX PKs were estimated by standard noncompartmental analysis. Linear regression determined which serum creatinine‐ or cystatin C‐based eGFR equation best predicted MTX clearance. The 80 included patients had a median (interquartile range [IQR]) age of 68.6 years (IQR 59.2–75.6), 54 (67.5%) were men, and 74 (92.5%) were White. The median (IQR) dose of MTX was 7.6 (IQR 4.8–11.3) grams. Median clearance was similar across three dosing levels at 4.5–5.6 L/h and was consistent with linear PKs. Liver function, weight, age, sex, concomitant chemotherapy, and number of previous MTX doses did not impact clearance. MTX area under the curve (AUC) values varied over a fourfold range and appeared to increase in proportion to the dose. The eGFRcys (ml/min) equation most closely correlated with MTX clearance in both the entire cohort and after excluding outlier MTX clearance values (r = 0.31 and 0.51, respectively). HDMTX as a 4‐h infusion displays high interpatient pharmacokinetic variability. Population PK modeling to optimize MTX AUC attainment requires further evaluation. The cystatin C‐based eGFR equation most closely estimated MTX clearance and should be investigated for dosing and monitoring in adults requiring MTX as part of lymphoma management.

Objective: To assess 4 adverse renal outcomes in a heterogeneous cohort of patients with systolic heart failure (HF) who were prescribed sacubitril-valsartan vs angiotensin-converting enzyme inhibitor/angiotensin receptor blocker (ACEi/ARB). Patients and Methods: The OptumLabs Database Warehouse, which contains linked administrative claims and laboratory results, was used to identify patients with systolic HF who were prescribed sacubitril-valsartan or ACEi/ARB between July 1, 2015, and September 30, 2019. One-to-one propensity score matching and inverse probability of treatment weighting was used to balance baseline variables. Cox proportional hazards modeling was performed to compare renal outcomes in both medication groups, including 30% or more decline in estimated glomerular filtration rate (eGFR), doubling of serum creatinine, acute kidney injury (AKI), and kidney failure (eGFR < 15 mL/min per 1.73 m2, kidney transplant, or dialysis initiation). Results: A total of 4667 matched pairs receiving sacubitril-valsartan or ACEi/ARB were included; the mean follow-up period was 7.8±7.8 months. The mean age was 69.4±11 years; 35% were female, 19% black, and 15% Hispanic. The cumulative risk at 1 year was 6% for 30% or more decline in eGFR, 2% for doubling of serum creatinine, 3% for AKI, and 2% to 3% for kidney failure. Furthermore, no significant differences in risk were observed with sacubitril-valsartan compared with ACEi/ARB for a 30% or more decline in eGFR (hazard ratio [HR], 0.96; 95% CI, 0.79 to 1.10), doubling of serum creatinine (HR, 0.94; 95% CI, 0.69 to 1.27); AKI (HR, 0.80; 95% CI, 0.63 to 1.03), and kidney failure (HR 0.80; 95% CI, 0.59 to 1.08). Conclusion: Among patients with systolic HF, the risk of adverse renal outcomes was similar between patients prescribed sacubitril-valsartan and those prescribed ACEi/ARB.

Abstract Background Beta-lactams (i.e., penicillins, cephalosporins, carbapenems, monobactams) are the most widely used class of antibiotics in critically ill patients. There is substantial interpatient variability in beta-lactam pharmacokinetics which renders their effectiveness and safety largely unpredictable. One strategy to ensure achievement of therapeutic concentrations is drug level testing (“therapeutic drug monitoring”; TDM). While studies have suggested promise with beta-lactam TDM, it is not yet widely available or implemented. This protocol presents a mixed-methods study designed to examine healthcare practitioners’ perspectives on the use and implementation of beta-lactam TDM in the critically ill. Methods An explanatory sequential mixed-methods design will be used [QUANT → qual]. First, quantitative data will be collected through a web-based questionnaire directed at clinicians at three academic medical centers at different phases of beta-lactam TDM implementation (not yet implemented, partially implemented, fully implemented). The sampling frame will include providers from a variety of disciplines that interact with drug level testing and interpretation in the critical care environment including pharmacists, intensivists, infectious diseases experts, medical/surgical trainees, and advanced practice providers. Second, approximately 30 individuals will be purposively sampled from survey respondents to conduct in-depth qualitative interviews to explain and expand upon the results from the quantitative strand. Normalization Process Theory and the Consolidated Framework for Implementation Science will be used to guide data analysis. Discussion These data will be used to answer two specific questions: “What are ICU practitioners’ perspectives on implementing beta-lactam TDM?” and “What factors contribute to the success of beta-lactam TDM program implementation?” Results of this study will be used to design future implementation strategies for beta-lactam TDM programs in the critically ill. Trial registration NCT04755777 .

Abstract Background Primary hyperoxaluria type 1 (PH1) is associated with nephrocalcinosis (NC) and calcium oxalate (CaOx) kidney stones (KS). Populations of urinary extracellular vesicles (EVs) can reflect kidney pathology. The aim of this study was to determine whether urinary EVs carrying specific biomarkers and proteins differ among PH1 patients with NC, KS or with neither disease process. Methods Mayo Clinic Rare Kidney Stone Consortium bio-banked cell-free urine from male and female PH1 patients without (n = 10) and with NC (n = 6) or KS (n = 9) and an eGFR > 40 mL/min/1.73 m2 were studied. Urinary EVs were quantified by digital flow cytometer and results expressed as EVs/ mg creatinine. Expressions of urinary proteins were measured by customized antibody array and results expressed as relative intensity. Data were analyzed by ANCOVA adjusting for sex, and biomarkers differences were considered statistically significant among groups at a false discovery rate threshold of Q

Abstract Background Prior papers have been inconsistent regarding how much creatinine clearance (CrCl) overestimates glomerular filtration rate (GFR). A recent cross-sectional study suggested that measurement error alone could entirely account for the longstanding observation that CrCl/GFR ratio is larger when GFR is lower among patients with chronic kidney disease (CKD); but there have been no validation of this in other cohorts. Methods To fill these gaps in knowledge regarding the relation between CrCl and GFR, we conducted cross-sectional and longitudinal analysis of the Modification of Diet in Renal Disease study (MDRD) and African American Study of Kidney Disease and Hypertension (AASK); and cross-sectional analysis of a clinical dataset from the Mayo Clinic of four different patient populations (CKD patients, kidney transplant recipients, post kidney donation subgroup and potential kidney donors). In the cross-sectional analyses (MDRD, AASK and Mayo Clinic cohort), we examined the relation between the CrCl/iothalamate GFR (iGFR) ratio at different categories of iGFR or different levels of CrCl. In the MDRD and AASK longitudinal analyses, we studied how the CrCl/iGFR ratio changed with those who had improvement in iGFR (CrCl) over time versus those who had worsening of iGFR (CrCl) over time. Results Observed CrCl/iGFR ratios were generally on the lower end of the range reported in the literature for CKD (median 1.24 in MDRD, 1.13 in AASK and 1.25 in Mayo Clinic cohort). Among CKD patients in whom CrCl and iGFR were measured using different timed urine collections, CrCl/iGFR ratio were higher with lower iGFR categories but lower with lower CrCl categories. However, among CKD patients in whom CrCl and iGFR were measured using the same timed urine collections (which reduces dis-concordant measurement error), CrCl/iGFR ratio were higher with both lower iGFR categories and lower CrCl categories. Conclusions These data refute the recent suggestion that measurement error alone could entirely account for the longstanding observation that CrCl/GFR ratio increases as GFR decreases in CKD patients. They also highlight the lack of certainty in our knowledge with regard to how much CrCl actually overestimates GFR.

Background: Acute kidney injury (AKI) survivors are at heightened risk for poor short- and long-term health outcomes. Even among those who recover after an AKI episode, the risk for chronic kidney disease is 4- to 6-fold higher than in patients without AKI, underscoring the importance of identifying methods to improve AKI survivorship. Objective: The purpose of this report was to describe the development and feasibility of a novel multidisciplinary approach to caring for AKI survivors at care transitions (ACT). Design: Observational process improvement initiative. Setting: Single academic medical center in the United States. Patients: The studied population was adults with stage 3 AKI not discharging on dialysis who were established with a primary care provider (PCP) at our institution. Methods: An electronic health record tool was developed prior to implementation to identify AKI survivors. The ACT program encompassed engaging patients in the hospital, delivering education by nephrology-trained nurses before discharge, completing recommended laboratory testing after discharge, and conducting structured kidney-focused follow-up with a pharmacist and a PCP within 7 to 14 days after discharge. Patients could be referred for nephrology evaluation at the discretion of the PCP. Results: Preliminary data demonstrated that most AKI survivors of interest could be identified, educated, and followed up with this model. This strategy appeared feasible, scalable, and maximized the unique expertise of each member of the multidisciplinary team. Limitations: Small sample size, future assessment of process, clinical, and patient-reported outcomes needed. Conclusions: The multidisciplinary ACT workflow supported by clinical decision support was feasible and addressed gaps in existing care transition models. Team-based care delivery in primary care appears to be a mechanism to extend the capacity for kidney health monitoring for AKI survivors.

Background. Improving both patient and graft survival after kidney transplantation are major unmet needs. The goal of this study was to assess risk factors for specific causes of graft loss to determine to what extent patients who develop either death with a functioning graft (DWFG) or graft failure (GF) have similar baseline risk factors for graft loss. Methods. We retrospectively studied all solitary renal transplants performed between January 1, 2006, and December 31, 2018, at 3 centers and determined the specific causes of DWFG and GF. We examined outcomes in different subgroups using competing risk estimates and cause-specific Cox models. Results. Of the 5752 kidney transplants, graft loss occurred in 21.6% (1244) patients, including 12.0% (691) DWFG and 9.6% (553) GF. DWFG was most commonly due to malignancy (20.0%), infection (19.7%), cardiac disease (12.6%) with risk factors of older age and pretransplant dialysis, and diabetes as the cause of renal failure. For GF, alloimmunity (38.7%), glomerular diseases (18.6%), and tubular injury (13.9%) were the major causes. Competing risk incidence models identified diabetes and older recipients with higher rates of both DWFG and nonalloimmune GF. Conclusions. These data suggest that at baseline, 2 distinct populations can be identified who are at high risk for renal allograft loss: a younger, nondiabetic patient group who develops GF due to alloimmunity and an older, more commonly diabetic population who develops DWFG and GF due to a mixture of causes—many nonalloimmune. Individualized management is needed to improve long-term renal allograft survival in the latter group.

Background. Nephrolithiasis in living kidney donors is concerning due to the potential impact on long-term postdonation kidney function. Methods. We performed a cohort study of living kidney donors from 2 centers with a baseline computed tomography scan and implantation renal biopsy. Donors (>5 y since donation) completed a follow-up survey or underwent chart review to assess eGFR and incident hypertension. Stone formers were classified as symptomatic if they had a past symptomatic episode or asymptomatic if only incidental radiographic kidney stones were identified during donor evaluation. We compared baseline clinical, imaging, and biopsy characteristics by stone former status including review of metabolic evaluations in stone formers. Long-term risks of renal complications (low eGFR and hypertension) by stone former status were evaluated. Results. There were 12 symptomatic and 76 asymptomatic stone formers among 866 donors. Overall, baseline clinical characteristics and implantation biopsy findings were similar between stone formers and non-stone formers. After a median follow-up of 10 y, stone former status was not associated with eGFR

An amendment to this paper has been published and can be accessed via the original article.

Abstract Methods for estimating nephron number in a clinical setting may be useful for predicting renal outcomes. This study aimed to establish such a method using unenhanced computed tomography (CT) and biopsy-based stereology. Patients or living kidney donors simultaneously subjected to enhanced and unenhanced CT examinations were randomly assigned to development and validation groups. The enhanced CT-measured arterial phase and the venous phase images of kidneys were regarded as the true values for cortical volume and parenchymal volume, respectively. Linear multiple regression analysis was used to create models for estimating cortical volume using explanatory variables including unenhanced CT-measured parenchymal volume. Nephron number was determined as the product of cortical volume and the glomerular density in biopsies of donors. Five equations for estimating cortical volume were created and verified. In donors, estimated nephron number by unenhanced CT was consistent with that by enhanced CT, with minimal errors in all models (636–655 ± 210–219 vs. 648 ± 224 × 103/kidney). Clinical characteristics combined with parenchymal volume did not improve the equation over parenchymal volume alone. These results support the feasibility of estimating nephron number by a combination of unenhanced CT and biopsy-based stereology, with a possible application for renal disease patients who are often not suitable for contrast media.

Rationale & Objective: The number of glomeruli is often used to determine the adequacy of a kidney biopsy (eg, at least 10 glomeruli). It is often assumed that biopsy specimens with limited amounts of cortex are too imprecise for detection of focal pathology. Study Design: Clinical-pathologic correlation (cross-sectional). Setting & Participants: Living kidney donors who underwent a needle core biopsy of their kidney at the time of donation. Exposure: The amount of cortex biopsied as determined by either the number of glomeruli or area of cortex on histology. Outcome: The percentage of globally sclerotic glomeruli, density of interstitial fibrosis foci, and severity of arteriosclerosis were determined. Analytical approach: A beta-binomial model assessed how the mean percentage of globally sclerotic glomeruli and patient variability in percentage of globally sclerotic glomeruli differed with the number of glomeruli on the biopsy specimen. Additional models assessed the association of interstitial fibrosis and arteriosclerosis with number of glomeruli. Results: There were 2,915 kidney donors studied. Fewer glomeruli on the biopsy specimen associated with higher mean percentage of globally sclerotic glomeruli and higher patient variability in percentage of globally sclerotic glomeruli. Smaller cortical volume on imaging correlated with both less cortex on biopsy and higher percentage of globally sclerotic glomeruli. Based on a statistical simulation, the probability of patient percentage of globally sclerotic glomeruli ≥ 10% if the biopsy percentage of globally sclerotic glomeruli is ≥10% (positive predictive value) was 45% with 1 to 9 glomeruli versus 31% with 10 or more glomeruli; the negative predictive value was 91% versus 98%. Fewer glomeruli also associated with more interstitial fibrosis and arteriosclerosis. Limitations: The study was limited to living kidney donors. Patient variability in percentage of globally sclerotic glomeruli was based on a statistical model because multiple biopsy specimens per patient were not available. Conclusions: The amount of cortex on a needle core biopsy is not completely random. Chronic changes from loss of cortex contribute to low amounts of cortex on a kidney biopsy specimen. Index Words: Renal pathology, renal morphometry, renal cortex, glomeruli, glomerulosclerosis, kidney biopsy

OBJECTIVES:. Beta-lactam antibiotics exhibit high interindividual variability in drug concentrations in patients with critical illness which led to an interest in the use of therapeutic drug monitoring to improve effectiveness and safety. To implement therapeutic drug monitoring, it is necessary to define the beta-lactam therapeutic range—in essence, what drug concentration would prompt a clinician to make dose adjustments up or down. This objective of this narrative review was to summarize evidence for the “floor” (for effectiveness) and “ceiling” (for toxicity) for the beta-lactam therapeutic range to be used with individualized therapeutic drug monitoring. DATA SOURCES:. Research articles were sourced from PubMed using search term combinations of “pharmacokinetics,” “pharmacodynamics,” “toxicity,” “neurotoxicity,” “therapeutic drug monitoring,” “beta-lactam,” “cefepime,” “meropenem,” “piperacillin/tazobactam,” “ICU,” and “critical illness.” STUDY SELECTION:. Articles were selected if they included preclinical, translational, or clinical data on pharmacokinetic and pharmacodynamic thresholds for effectiveness and safety for beta-lactams in critical illness. DATA SYNTHESIS:. Experimental data indicate a beta-lactam concentration above the minimum inhibitory concentration of the organism for greater than or equal to 40–60% of the dosing interval is needed, but clinical data indicate that higher concentrations may be preferrable. In the first 48 hours of critical illness, a free beta-lactam concentration at or above the susceptibility breakpoint of the most likely pathogen for 100% of the dosing interval would be reasonable (typically based on Pseudomonas aeruginosa). After 48 hours, the lowest acceptable concentration could be tailored to 1–2× the observed minimum inhibitory concentration of the organism for 100% of the dosing interval (often a more susceptible organism). Neurotoxicity is the primary dose-dependent adverse effect of beta-lactams, but the evidence remains insufficient to link a specific drug concentration to greater risk. CONCLUSIONS:. As studies advance the understanding of beta-lactam exposure and response in critically ill patients, it is essential to clearly define the acceptable therapeutic range to guide regimen selection and adjustment.

Routine preventive cancer screening is not recommended for patients with end-stage renal disease (ESRD)11 Notable abbreviations: primary care (PC), End Stage Renal Disease (ESRD), United States Renal Data System (USRDS). due to their limited life expectancy. The current extent of cancer screening in this population is unknown. Primary care (PC) reminder systems or performance incentives may encourage indiscriminate cancer screening. We compared rates of cancer screening in patients with ESRD, with and without PC visits. This is a retrospective cohort study using United States Renal Data System (USRDS) billing data and electronic medical record data. Patients aged ≥18 years starting dialysis from 2001 to 2008, Midwest regional dialysis network were categorized with or without a PC visit (defined as an office visit in family practice, internal medicine, pediatrics, geriatrics or preventive medicine during the first two years of dialysis). Cancer screening was based on Current Procedural Terminology codes in USRDS. We identified 2512 incident dialysis patients (60% men, median age 65y). Cancer screening rates were more frequent among those seen in PC: 38% vs 19% (P = 0.0002), for breast; 18% vs 10% (P = 0.047) for cervical; 13% versus 8% (P = 0.024) for prostate; and 18% vs 9% (P = 0.0002) for colon cancer. Multivariable analyses found that those with PC were more likely to be screened after adjusting for age, sex, and comorbidities.In our practice, cancer screening rates among chronic dialysis patients are lower than those previously reported for our general population (64% for breast cancer). However, a sizeable proportion of our ESRD population does receive cancer screening, especially those still seen in primary care. Keywords: Breast cancer screening, Cervical cancer screening, Colon cancer screening, Dialysis, ESRD, Preventive screening, Prostate cancer screening

The data presented in this article are related to the research article entitled “The Diagnostic Value of Rescaled Renal Biomarkers Serum Creatinine and Serum Cystatin C and their Relation with Measured Glomerular Filtration Rate” (Pottel et al. (2017) [1]). Data are presented demonstrating the rationale for the normalization or rescaling of serum cystatin C, equivalent to the rescaling of serum creatinine. Rescaling biomarkers brings them to a notionally common scale with reference interval [0.67–1.33]. This article illustrates the correlation between rescaled biomarkers serum creatinine and serum cystatin C by plotting them in a 2-dimensional graph. The diagnostic value in terms of sensitivity and specificity with measured Glomerular Filtration Rate as the reference method is calculated per age-decade for both rescaled biomarkers. Finally, the interchangeability between detecting impaired kidney function from renal biomarkers and from the Full Age Spectrum FAS-estimating GFR-equation and measured GFR using a fixed and an age-dependent threshold is shown.

Non-invasive tests to identify age and early disease-associated pathology within the kidney are needed. Specific populations of urinary extracellular vesicles (EVs) could potentially be used for such a diagnostic test. Random urine samples were obtained from age- and sex-stratified living kidney donors before kidney donation. A biopsy of the donor kidney was obtained at the time of transplantation to identify nephron hypertrophy (larger glomerular volume, cortex per glomerulus and mean profile tubular area) and nephrosclerosis (% fibrosis, % glomerulosclerosis and arteriosclerosis). Renal parenchymal-derived EVs in cell-free urine were quantified by digital flow cytometry. The relationship between these EV populations and structural pathology on the kidney biopsy was assessed. Clinical characteristics of the kidney donors (n=138, age range: 20–70 years, 50% women) were within the normative range. Overall, urine from women contained more EVs than that from men. The number of exosomes, juxtaglomerular cells and podocyte marker–positive EVs decreased (p

Pharmacists are at the forefront of dosing and monitoring medications eliminated by or toxic to the kidney. To evaluate the effectiveness and safety of these medications, accurate measurement of kidney function is paramount. The mainstay of kidney assessment for drug dosing and monitoring is serum creatinine (SCr)-based estimation equations. Yet, SCr has known limitations including its insensitivity to underlying changes in kidney function and the numerous non-kidney factors that are incompletely accounted for in equations to estimate glomerular filtration rate (eGFR). Serum cystatin C (cysC) is a biomarker that can serve as an adjunct or alternative to SCr to evaluate kidney function for drug dosing. Pharmacists must be educated about the strengths and limitations of cysC prior to applying it to medication management. Not all patient populations have been studied and some evaluations demonstrated large variations in the relationship between cysC and GFR. Use of eGFR equations incorporating cysC should be reserved for drug management in scenarios with demonstrated outcomes, including to improve pharmacodynamic target attainment for antibiotics or reduce drug toxicity. This article provides an overview of cysC, discusses evidence around its use in medication dosing and in special populations, and describes practical considerations for application and implementation.

High-dose methotrexate (MTX; ≥1 g/m2) is a renally eliminated and nephrotoxic first-line therapy for central nervous system (CNS) lymphoma. Creatinine-based estimation of renal function is the recommended approach to dosing MTX in these cases, but nonrenal determinants of creatinine production and elimination in cancer patients such as malnutrition and cachexia lead to overestimation of glomerular filtration rate (GFR) by this method and a heightened risk for drug toxicity. Serum cystatin C is one of the first readily available, relatively inexpensive, endogenous biomarkers to emerge as a practical adjunct to creatinine for estimation of renal function for drug dosing. In this report, we describe two cases where cystatin C was used in conjunction with creatinine to inform MTX dosing for CNS lymphoma. In both cases, the estimated GFR was nearly 40% lower with the combination of the two biomarkers compared to creatinine-only estimates. Empiric MTX dose reductions as a product of these results likely spared the patients sustained exposure to toxic drug concentrations and facilitated earlier administration of supportive care interventions. Further prospective investigations with validated dosing regimens including cystatin C are warranted for high-dose MTX.

Abstract Aging is a nearly universal phenomenon in biology only partially controlled by genetic endowment. Individuals and their organs age at varying rates. The kidneys manifest the aging process by steady loss of nephrons and a corresponding decrease in glomerular filtration rate (GFR) beginning about age 30 years. The mechanisms responsible for this observation is are elusive. However, defining chronic kidney disease based on arbitrary, fixed thresholds of GFR in the later phases of life can be problematical as it may over-diagnosis CKD in the elderly. A modest, persisting reduction of GFR (around 45-59 ml/min/1.73m2) without abnormal proteinuria does not seem to confer much of an adverse effect on mortality and remaining life expectancy in older adults and the development of end-stage renal disease in such subjects is very uncommon. Old kidneys should not be equated with "diseased" kidneys.