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Background Serum cystatin C–based estimated glomerular filtration rate (eGFRcys) generally associates with clinical outcomes better than serum creatinine–based eGFR (eGFRcr) despite similar precision in estimating measured GFR (mGFR). We sought to determine whether the risk of adverse outcomes with eGFRcr or eGFRcys was via GFR alone or also via non-GFR determinants among kidney transplant recipients. Methods Consecutive adult kidney transplant recipients underwent a standardized GFR assessment during a routine follow-up clinic visit between 2011 and 2013. Patients were followed for graft failure or the composite outcome of cardiovascular (CV) events or mortality through 2020. The risk of these events by baseline mGFR, eGFRcr and eGFRcys was assessed unadjusted, adjusted for mGFR and adjusted for CV risk factors. Results There were 1135 recipients with a mean baseline mGFR of 55.6, eGFRcr of 54.8 and eGFRcys of 46.8 ml/min/1.73 m2 and a median follow-up of 6 years. Each 10 ml/min/1.73 m2 decrease in mGFR, eGFRcr or eGFRcys associated with graft failure [hazard ratio (HR) 1.79, 1.68 and 2.07, respectively; P Conclusion eGFRcr better represents the true relationship between GFR and outcomes after kidney transplantation because it has less non-GFR residual association. Cystatin C is better interpreted as a nonspecific prognostic biomarker than is eGFR in the kidney transplant setting.

New Equations for Estimating GFR without Race Equations for estimating GFR with serum creatinine overestimate measured GFR in Blacks. The authors report new equations, without race as an inflation factor, using cystatin C and creatinine that reduced errors in estimation between Black participants and non-Black participants.Background Current equations for estimated glomerular filtration rate (eGFR) that use serum creatinine or cystatin C incorporate age, sex, and race to estimate measured GFR. However, race in eGFR equations is a social and not a biologic construct. Methods We developed new eGFR equations without race using data from two development data sets: 10 studies (8254 participants, 31.5% Black) for serum creatinine and 13 studies (5352 participants, 39.7% Black) for both serum creatinine and cystatin C. In a validation data set of 12 studies (4050 participants, 14.3% Black), we compared the accuracy of new eGFR equations to measured GFR. We projected the prevalence of chronic kidney disease (CKD) and GFR stages in a sample of U.S. adults, using current and new equations. Results In the validation data set, the current creatinine equation that uses age, sex, and race overestimated measured GFR in Blacks (median, 3.7 ml per minute per 1.73 m(2) of body-surface area; 95% confidence interval [CI], 1.8 to 5.4) and to a lesser degree in non-Blacks (median, 0.5 ml per minute per 1.73 m(2); 95% CI, 0.0 to 0.9). When the adjustment for Black race was omitted from the current eGFR equation, measured GFR in Blacks was underestimated (median, 7.1 ml per minute per 1.73 m(2); 95% CI, 5.9 to 8.8). A new equation using age and sex and omitting race underestimated measured GFR in Blacks (median, 3.6 ml per minute per 1.73 m(2); 95% CI, 1.8 to 5.5) and overestimated measured GFR in non-Blacks (median, 3.9 ml per minute per 1.73 m(2); 95% CI, 3.4 to 4.4). For all equations, 85% or more of the eGFRs for Blacks and non-Blacks were within 30% of measured GFR. New creatinine-cystatin C equations without race were more accurate than new creatinine equations, with smaller differences between race groups. As compared with the current creatinine equation, the new creatinine equations, but not the new creatinine-cystatin C equations, increased population estimates of CKD prevalence among Blacks and yielded similar or lower prevalence among non-Blacks. Conclusions New eGFR equations that incorporate creatinine and cystatin C but omit race are more accurate and led to smaller differences between Black participants and non-Black participants than new equations without race with either creatinine or cystatin C alone. (Funded by the National Institute of Diabetes and Digestive and Kidney Diseases.)

Objective To compare coronavirus disease 2019 (COVID-19) acute kidney injury (AKI) to sepsis-AKI (S-AKI). The morphology and transcriptomic and proteomic characteristics of autopsy kidneys were analyzed. Patients and Methods Individuals 18 years of age and older who died from COVID-19 and had an autopsy performed at Mayo Clinic between April 2020 to October 2020 were included. Morphological evaluation of the kidneys of 17 individuals with COVID-19 was performed. In a subset of seven COVID-19 cases with postmortem interval of less than or equal to 20 hours, ultrastructural and molecular characteristics (targeted transcriptome and proteomics analyses of tubulointerstitium) were evaluated. Molecular characteristics were compared with archived cases of S-AKI and nonsepsis causes of AKI. Results The spectrum of COVID-19 renal pathology included macrophage-dominant microvascular inflammation (glomerulitis and peritubular capillaritis), vascular dysfunction (peritubular capillary congestion and endothelial injury), and tubular injury with ultrastructural evidence of mitochondrial damage. Investigation of the spatial architecture using a novel imaging mass cytometry revealed enrichment of CD3+CD4+ T cells in close proximity to antigen-presenting cells, and macrophage-enriched glomerular and interstitial infiltrates, suggesting an innate and adaptive immune tissue response. Coronavirus disease 2019 AKI and S-AKI, as compared to nonseptic AKI, had an enrichment of transcriptional pathways involved in inflammation (apoptosis, autophagy, major histocompatibility complex class I and II, and type 1 T helper cell differentiation). Proteomic pathway analysis showed that COVID-19 AKI and to a lesser extent S-AKI were enriched in necroptosis and sirtuin-signaling pathways, both involved in regulatory response to inflammation. Upregulation of the ceramide-signaling pathway and downregulation of oxidative phosphorylation in COVID-19 AKI were noted. Conclusion This data highlights the similarities between S-AKI and COVID-19 AKI and suggests that mitochondrial dysfunction may play a pivotal role in COVID-19 AKI. This data may allow the development of novel diagnostic and therapeutic targets.

Background Beta-lactam therapeutic drug monitoring (BL TDM; drug level testing) can facilitate improved outcomes in critically ill patients. Yet less than 20% of hospitals have implemented BL TDM. The purpose of this study was to characterize provider perceptions and key considerations for successful implementation of BL TDM. Methods This was a sequential mixed methods study from 2020 to 2021 of stakeholders at three academic medical centers with varying degrees of BL TDM implementation - Mayo Clinic (BL TDM not implemented), University of Florida Health Shands (partially implemented), and Royal Brisbane and Women’s Hospital (fully implemented). Stakeholders completed a survey to characterize their knowledge, perceptions, and experience with BL TDM. A diverse group of 30 respondents were then purposively sampled for semi-structured interviews. Results from the two strands were integrated, themes were identified, and findings were situated within implementation science frameworks. Results Among the 138 survey respondents (22% response rate), the majority were physicians (38%) and pharmacists (33%). 71% practiced in critical care and 21% in infectious diseases. The majority of respondents felt BL TDM was relevant to their practice and improved medication effectiveness and safety (Figure 1). Two implementation themes were identified: individual internalization and organizational features. Individuals needed to internalize, make sense of, and agree to BL TDM implementation which was positively influenced by repeated exposure to evidence and expertise. The process of internalization seemed more complex with BL TDM than with other antibiotics (i.e., vancomycin). Organizational considerations relevant to BL TDM implementation included adequate physical and informational infrastructure, access to trained personnel, supportive governance/leadership, and robust process and workflow development. Conclusion We found broad enthusiasm about the relevance and potential benefits of BL TDM among stakeholders. Prior literature suggested the primary barrier to implementation was assay availability, but we identified many more individual and organizational attributes which impacted the scale and spread of BL TDM. Disclosures Sara Ausman, PharmD, Gilead: Honoraria Christina G. Rivera, PharmD, Gilead: Grant/Research Support|Gilead: Honoraria|Insmed: Honoraria Jason Roberts, BPharm(Hons), PhD, FSHP, FISAC, British Society of Chemotherapy: Grant/Research Support|Cipla: Honoraria|Gilead: Advisor/Consultant|MSD: Advisor/Consultant|MSD: Honoraria|Pfizer: Board Member|Pfizer: Honoraria|Qpex: Grant/Research Support|Sandoz: Board Member|Summit: Advisor/Consultant|Wolters Kluwer: Advisor/Consultant Marc H. Scheetz, PharmD, MSc, Abbvie: Advisor/Consultant|Allecra: Grant/Research Support|Merck: Advisor/Consultant|Nevakar: Advisor/Consultant|Nevakar: Grant/Research Support|Premier Healthcare Solutions: Honoraria|Spero: Advisor/Consultant|SuperTrans Medical: Advisor/Consultant|SuperTrans Medical: Grant/Research Support|Takeda: Advisor/Consultant|Third Pole Therapeutics: Advisor/Consultant.

Ultrasound is a key imaging tool for the evaluation of the kidney. Over the last two decades, methods to measure the mechanical properties of soft tissues have been developed and used in clinical practice, though the use in the kidney has not been as widespread as for other applications. The mechanical properties of the kidney are determined by the structure and composition of the renal parenchyma as well as the perfusion characteristics. As pathological processes change these factors, the mechanical properties change and can be used for diagnostic purposes as well as monitoring treatment or disease progression. Ultrasound-based elastography methods for evaluating the mechanical properties of the kidney use focused ultrasound beams to perturb the kidney and then high frame rate ultrasound methods are used to measure the resulting motion. The motion is analyzed to estimate the mechanical properties. This review will describe the principles of these methods and discuss several seminal studies related to characterizing the kidney. Additionally, an overview of the clinical use of elastography methods in native and kidney allografts will be provided. Perspectives on future developments and uses of elastography technology along with other complementary ultrasound imaging modalities will be provided.

RATIONALE & OBJECTIVE: While there are several well-known anatomical and physiological changes during pregnancy that could contribute to kidney stone formation, evidence that they increase the risk of kidney stones during pregnancy is lacking. This study aimed to determine whether there was an increased risk of a first-time symptomatic kidney stone during and after pregnancy. STUDY DESIGN: A population-based matched case-control study. SETTING & PARTICIPANTS: 945 female first-time symptomatic kidney stone formers aged 15–45 years and 1,890 age-matched female controls in Olmsted County, Minnesota from 1984–2012. Index date was the date of onset of a symptomatic kidney stone for both the case and their matched controls. EXPOSURE: The primary exposure was pregnancy with assessment for variation in risk across different time intervals before, during, and after pregnancy. Medical records were manually reviewed to determine the conception and delivery dates for pregnancies. OUTCOME: Medical record-validated first-time symptomatic kidney stone. ANALYTIC APPROACH: Conditional and unconditional multivariable logistic regression analysis. RESULTS: Compared to non-pregnant women, the odds of a symptomatic kidney stone in women was similar in the first trimester (OR, 0.92; p=0.8), began to increase during the second trimester (OR, 2.00; p=0.007), further increased during the third trimester (OR, 2.69; p=0.001), peaked at 0–3 months after delivery (OR, 3.53; p1 year ago) was also associated with a first-time symptomatic kidney stone (OR, 1.27; p=0.01). LIMITATIONS: Observational study design in predominantly white population. The exact timing of stone formation cannot be determined. CONCLUSIONS: Pregnancy increases the risk of a first-time symptomatic kidney stone. This risk peaks close to delivery and then improves by 1 year after delivery, though a modest risk of a kidney stone still exists beyond 1 year after delivery.

Background The class of antibiotics known as β-lactams are a commonly used due to their effectiveness and safety. Therapeutic drug monitoring has been proposed but requires an accurate assay along with well-characterized preanalytic stability, as β-lactams are known to be relatively unstable. Methods A high-throughput LC-MS/MS assay validation and stability study was performed for cefepime, meropenem, and piperacillin and tazobactam in serum. Patient samples, standards, and QCs were crashed with acetonitrile containing internal standard. Following centrifugation, an aliquot of the supernatant was diluted with clinical laboratory reagent water and analyzed by LC-MS/MS. Results The assay showed linearity between 0.5 and 60 µg/mL for each analyte. The intra- and interassay reproducibility at 3 different concentrations (approximately 2, 25, and 40 µg/mL) was Conclusions The LC-MS/MS assay showed acceptable performance characteristics for quantitation of β-lactams. With well-characterized stability, this assay can be used with residual specimens for pharmacokinetic modeling, which may lead to individualized dosing and improved patient care.

SARS-CoV-2 infection has become a major public health burden and affects many organs including lungs, kidneys, the liver, and the brain. Although the virus is readily detected and diagnosed using nasopharyngeal swabs by reverse transcriptase polymerase chain reaction (RT-PCR), detection of its presence in body fluids is fraught with difficulties. A number of published studies have failed to detect viral RNA by RT-PCR methods in urine. Although microbial identification in clinical microbiology using mass spectrometry is undertaken after culture, here we undertook a mass spectrometry-based approach that employed an enrichment step to capture and detect SARS-CoV-2 nucleocapsid protein directly from urine of COVID-19 patients without any culture. We detected SARS-CoV-2 nucleocapsid protein-derived peptides from 13 out of 39 urine samples. Further, a subset of COVID-19 positive and COVID-19 negative urine samples validated by mass spectrometry were used for the quantitative proteomics analysis. Proteins with increased abundance in urine of SARS-CoV-2 positive individuals were enriched in the acute phase response, regulation of complement system, and immune response. Notably, a number of renal proteins such as podocin (NPHS2), an amino acid transporter (SLC36A2), and sodium/glucose cotransporter 5 (SLC5A10), which are intimately involved in normal kidney function, were decreased in the urine of COVID-19 patients. Overall, the detection of viral antigens in urine using mass spectrometry and alterations of the urinary proteome could provide insights into understanding the pathogenesis of COVID-19.

The population is aging. Although older adults have higher rates of comorbidities and adverse health events, they represent a heterogeneous group with different health trajectories. Frailty, a clinical syndrome of decreased physiological reserve and increased susceptibility to illness and death, has emerged as a potential risk stratification tool in older patients with chronic kidney disease (CKD). Frailty is commonly observed in patients with CKD and associated with numerous adverse outcomes, including falls, decreased quality of life, hospitalizations, and death. Multiple pathologic factors contribute to the development of frailty in patients with CKD, including biological mechanisms of aging and physiological dysregulation. Current interventions to reduce frailty are promising, but additional investigations are needed to determine whether optimizing frailty measures improves renal and overall health outcomes. This review of frailty in CKD examines frailty definitions, the impact of frailty on health outcomes across the CKD spectrum, mechanisms of frailty, and antifrailty interventions (e.g., exercise or senescent cell clearance) tested in CKD patients. In addition, existing knowledge gaps, limitations of current frailty definitions in CKD, and challenges surrounding effective antifrailty strategies in CKD are considered.

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.

Background The Chronic Kidney Disease in Children Study (CKiD) equation for children and the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation for adults are recommended serum creatinine (SCr)-based calculations for estimating glomerular filtration rate (GFR). However, these equations, as well as their combination, have limitations, notably the problem of implausible changes in GFR during the transition from adolescence to adulthood and overestimation of GFR in young adults. The full age spectrum (FAS) equation addresses these issues but overestimates GFR when SCr levels are low. Objective To develop and validate a modified FAS SCr-based equation combining design features of the FAS and CKD-EPI equations. Design Cross-sectional analysis with separate pooled data sets for development and validation. Setting Research and clinical studies (n = 13) with measured GFR available. Patients 11 251 participants in 7 studies (development and internal validation data sets) and 8378 participants in 6 studies (external validation data set). Measurements Clearance of an exogenous marker (reference method), SCr level, age, sex, and height were used to develop a new equation to estimate GFR. Results The new European Kidney Function Consortium (EKFC) equation is a FAS equation with low bias (-1.2 mL/min/1.73 m2 [95% CI, -2.7 to 0.0 mL/min/1.73 m2] in children and -0.9 mL/min/1.73 m2 [CI, -1.2 to -0.5 mL/min/1.73 m2] in adults) across the FAS (2 to 90 years) and SCr range (40 to 490 µmol/L [0.45 to 5.54 mg/dL]) and with fewer estimation errors exceeding 30% (6.5% [CI, 3.8% to 9.1%] in children and 3.1% [CI, 2.5% to 3.6%] in adults) compared with the CKiD and CKD-EPI equations. Limitation No Black patients were included. Conclusion The new EKFC equation shows improved accuracy and precision compared with commonly used equations for estimating GFR from SCr levels. Primary funding source Swedish Research Council (Vetenskapsradet).

Objective To determine whether microstructural features on a kidney biopsy specimen obtained during kidney transplant surgery predict long-term risk of chronic kidney disease in the donor. Patients and Methods We studied kidney donors from May 1, 1999, through December 31, 2018, with a follow-up survey for the results of recent blood pressure and kidney function tests (estimated glomerular filtration rate [eGFR] and proteinuria). If not recently available, blood pressure and eGFRs were requested from a local clinic. Microstructural features on kidney biopsy at the time of donation were assessed as predictors of hypertension and kidney function after adjusting for years of follow-up, baseline age, sex, and clinical predictors. Results There were 807 donors surveyed a mean 10.5 years after donation. An eGFR less than 45 mL/min/1.73 m2 in 6.4% (43/673) of donors was predicted by larger glomerular volume per standard deviation (odds ratio [OR], 1.48; 95% CI, 1.08 to 2.04) and nephron number below the age-specific 5th percentile (OR, 3.38; 95% CI, 1.31 to 8.72). An eGFR less than 60 mL/min/1.73 m2 in 42.5% (286/673) of donors was not predicted by any microstructural feature. Residual eGFR (postdonation/predonation eGFR) was predicted by nephron number below the age-specific 5th percentile (difference, −6.07%; 95% CI, −10.24% to −1.89%). Self-reported proteinuria in 5.1% (40/786) of donors was predicted by larger glomerular volume (OR, 1.42; 95% CI, 1.08 to 1.86). Incident hypertension in 18.8% (119/633) of donors was not predicted by any microstructural features. Conclusion Low nephron number for age and larger glomeruli are important microstructural predictors for long-term risk of chronic kidney disease after living kidney donation.

Introduction: Acute kidney injury (AKI) affects 20% of hospitalized patients and worsens outcomes. To limit complications, post-discharge follow-up and kidney function testing are advised. The objective of this study was to evaluate the frequency of follow-up after discharge among AKI survivors. Methods: This was a population-based cohort study of adult Olmsted County residents hospitalized with an episode of stage II or III AKI between 2006 and 2014. Those dismissed from the hospital on dialysis, hospice, or who died within 30 days after discharge were excluded. The frequency and predictors of follow-up, defined as an outpatient serum creatinine (SCr) level or an in-person healthcare visit after discharge were described. Results: In the 627 included AKI survivors, the 30-day cumulative incidence of a follow-up outpatient SCr was 80% (95% confidence interval [CI]: 76% and 83%), a healthcare visit was 82% (95% CI: 79 and 85%), or both was 70% (95% CI: 66 and 73%). At 90 days and 1 year after discharge, the cumulative incidences of meeting both follow-up criteria rose to 82 and 91%, respectively. Independent predictors of receiving both an outpatient SCr assessment and healthcare visit within 30 days included lower estimated glomerular filtration rate at discharge, higher comorbidity burden, longer length of hospitalization, and greater maximum AKI severity. Age, sex, race/ethnicity, education level, and socioeconomic status did not predict follow-up. Conclusions: Among patients with moderate to severe AKI, 30% did not have follow-up with a SCr and healthcare visit in the 30-day post-discharge interval. Follow-up was associated with higher acuity of illness rather than demographic or socioeconomic factors.

Histology can provide insight into the biology of renal allograft loss. However, studies are lacking that use quantitative morphometry to simultaneously assess changes in mean glomerular volume and in the percentages of globally sclerosed glomeruli (GSG) and ischemic-appearing glomeruli in surveillance biopsies over time to determine whether such changes are correlated with late graft failure.We used digital scans of surveillance biopsies (at implantation and at 1 and 5 years after-transplantation) to morphometrically quantify glomerular volume and the percentages of GSG and ischemic-appearing glomeruli in a cohort of 835 kidney transplants. Cox proportional hazards models assessed the risk of allograft failure with these three glomerular features.From implantation to 5 years, mean glomerular volume increased by nearly 30% (from 2.8×10Glomerular changes reflect important pathologic processes that predict graft loss. Measuring glomerular changes quantitatively on surveillance biopsies, especially the proportion of ischemic-appearing glomeruli, may enhance the current Banff system and be a useful surrogate end point for clinical intervention trials.

Background Nephron hypertrophy and nephrosclerosis may be important determinants of CKD and mortality. However, studies of outcomes associated with these microstructural features have been limited to small tissue specimens from patients selected for either good kidney health or known kidney disease. Methods To determine whether microstructural features are predictive of progressive CKD and mortality outcomes, we studied patients who underwent a radical nephrectomy for a tumor. Large wedge sections of renal parenchyma distal to the tumor were stained and scanned into high-resolution images; we annotated the cortex and all glomeruli to calculate glomerular volume, cortex volume per glomerulus, and percentage of globally sclerotic glomeruli. Morphometric measurements also included percentages of artery luminal stenosis and interstitial fibrosis/tubular atrophy (IF/TA) of the cortex. At follow-up visits every 6-12 months, we determined which patients experienced progressive CKD (defined as dialysis, kidney transplantation, or a 40% decline from postnephrectomy eGFR). Cox models for these outcomes were adjusted for age, sex, body mass index, hypertension, diabetes, smoking, eGFR, and proteinuria. Results Among 936 patients (mean age, 64 years; postnephrectomy baseline eGFR, 48 ml/min per 1.73 m2), 117 progressive CKD events, 183 noncancer deaths, and 116 cancer deaths occurred during a median follow-up of 6.4 years. Larger glomerular volume, larger cortex per glomerulus, and higher percentage of globally sclerotic glomeruli or IF/TA predicted progressive CKD. Higher percentage IF/TA also predicted noncancer mortality. Microstructural features did not predict cancer mortality or recurrence. Conclusions After a radical nephrectomy, larger nephrons and nephrosclerosis predicted progressive CKD, and IF/TA predicted noncancer mortality. Morphometric analysis of renal parenchyma can predict noncancer clinical events in patients long after their radical nephrectomy.

The incidence and prevalence of kidney stones have increased over the past four decades. However, the diagnosis of 'kidney stone' can range from an incidental asymptomatic finding of limited clinical significance to multiple painful episodes of ureteral obstruction with eventual kidney failure. Some general strategies may be useful to prevent the recurrence of kidney stones. In particular, greater attention to kidney stone classification, approaches to assessing the risk of recurrence and individualized prevention strategies may improve the clinical care of stone formers. Although there have been some advances in approaches to predicting the recurrence of kidney stones, notable challenges remain. Studies of kidney stone prevalence, incidence and recurrence have reported inconsistent findings, in part because of the lack of a standardized stone classification system. A kidney stone classification system based on practical and clinically useful measures of stone disease may help to improve both the study and clinical care of stone formers. Any future kidney stone classification system should be aimed at distinguishing asymptomatic from symptomatic stones, clinically diagnosed symptomatic stone episodes from self-reported symptomatic stone episodes, symptomatic stone episodes that are confirmed from those that are suspected, symptomatic recurrence from radiographic recurrence (that is, with radiographic evidence of a new stone, stone growth or stone disappearance from presumed passage) and determine stone composition based on mutually exclusive categories.

Objective To characterize the use of cystatin C (cysC) across and within hospitals. Patients and Methods This 2-part study first evaluated access to cysC testing across 129 hospitals in the state of Minnesota, using a telephone-based survey. Second, granular data from a single center (Mayo Clinic) with on-site, rapid-turnaround testing ( Results Of the 114 hospitals (88%) that responded to the statewide survey, cysC was available in 91 (80%), but only 3 of 91 (3%) reported a turnaround time of Conclusion In the hospital, rapid-turnaround cysC testing is necessary for practical use but was not widely available in Minnesota. When available, a marked increase in cysC testing was observed over the study timeframe. Additional research is needed to determine optimal strategies for implementation of cysC within hospitals.

Background Nephrosclerosis, nephron size, and nephron number vary among kidneys transplanted from living donors. However, whether these structural features predict kidney transplant recipient outcomes is unclear. Methods Our study used computed tomography (CT) and implantation biopsy to investigate donated kidney features as predictors of death-censored graft failure at three transplant centers participating in the Aging Kidney Anatomy study. We used global glomerulosclerosis, interstitial fibrosis/tubular atrophy, artery luminal stenosis, and arteriolar hyalinosis to measure nephrosclerosis; mean glomerular volume, cortex volume per glomerulus, and mean cross-sectional tubular area to measure nephron size; and calculations from CT cortical volume and glomerular density on biopsy to assess nephron number. We also determined the death-censored risk of graft failure with each structural feature after adjusting for the predictive clinical characteristics of donor and recipient. Results The analysis involved 2293 donor-recipient pairs. Mean recipient follow-up was 6.3 years, during which 287 death-censored graft failures and 424 deaths occurred. Factors that predicted death-censored graft failure independent of both donor and recipient clinical characteristics included interstitial fibrosis/tubular atrophy, larger cortical nephron size (but not nephron number), and smaller medullary volume. In a subset with 12 biopsy section slides, arteriolar hyalinosis also predicted death-censored graft failure. Conclusions Subclinical nephrosclerosis, larger cortical nephron size, and smaller medullary volume in healthy donors modestly predict death-censored graft failure in the recipient, independent of donor or recipient clinical characteristics. These findings provide insights into a graft's "intrinsic quality" at the time of donation, and further support the use of intraoperative biopsies to identify kidney grafts that are at higher risk for failure.

This is the peer reviewed version of the following article: Delanaye, P., Björk, J., Courbebaisse, M., Couzi, L., Ebert, N., Eriksen, B.O., .... Nyman, U. (2021). Performance of creatinine-based equations to estimate glomerular filtration rate with a methodology adapted to the context of drug dosage adjustment. British Journal of Clinical Pharmacology, which has been published in final form at https://doi.org/10.1111/bcp.15132. This article may be used for non-commercial purposes in accordance with Wiley Terms and Conditions for Use of Self-Archived Versions. This article may not be enhanced, enriched or otherwise transformed into a derivative work, without express permission from Wiley or by statutory rights under applicable legislation. Copyright notices must not be removed, obscured or modified. The article must be linked to Wiley’s version of record on Wiley Online Library and any embedding, framing or otherwise making available the article or pages thereof by third parties from platforms, services and websites other than Wiley Online Library must be prohibited. Aim: The Cockcroft-Gault (CG) creatinine-based equation is still used to estimate glomerular filtration rate (eGFR) for drug dosage adjustment. Incorrect eGFR may lead to hazardous over- or underdosing. Methods: In a cross-sectional analysis, CG was validated against measured GFR (mGFR) in 14 804 participants and compared with the Modification-of-Diet-in-Renal-Diseases (MDRD), Chronic-Kidney-Disease-Epidemiology (CKD-EPI), Lund-Malmö-Revised (LMR) and European-Kidney-Function-Consortium (EKFC) equations. Validation focused on bias, imprecision and accuracy (percentage of estimates within ±30% of mGFR, P30), overall and stratified for mGFR, age and body mass index at mGFR Results: The CG equation performed worse than the other equations, overall and in mGFR, age and BMI subgroups in terms of bias (systematic overestimation), imprecision and accuracy except for patients ≥65 years where bias and P30 were similar to MDRD and CKD-EPI, but worse than LMR and EKFC. In subjects with mGFR 2, all equations performed similarly, and for BMI 2 CG and LMR had the best results though all equations had poor P30-accuracy. At BMI ≥ 25 kg/m2 the bias of the CG increased with increasing BMI (+17.2 mL/min at BMI ≥ 40 kg/m2). The four more recent equations also classified mGFR stages better than CG. Conclusions: The CG equation showed poor ability to estimate GFR overall and in analyses stratified for mGFR, age and BMI. CG was inferior to correctly classify the patients in the mGFR staging compared to more recent creatinine-based equations.

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.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).Observational process improvement initiative.Single academic medical center in the United States.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.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.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.Small sample size, future assessment of process, clinical, and patient-reported outcomes needed.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.Les patients qui survivent à un épisode d’insuffisance rénale aiguë (IRA) courent un risque plus élevé de mauvais résultats cliniques à court et à long terme. Même chez les patients qui se rétablissent, le risque de progression vers l’insuffisance rénale chronique (IRC) demeure de quatre à six fois plus élevé que chez les patients n’ayant jamais eu d’épisode d’IRA. Il est donc essentiel d’identifier des méthodes permettant d’améliorer la survie à un épisode d’IRA.L’objectif de cette étude était de décrire l’élaboration et la faisabilité d’une nouvelle approche multidisciplinaire pour la prise en charge des survivants d’un épisode d’IRA en transition de soins (Approche multidisciplinaire en Transition de Soins—AmTS).Initiative d’amélioration des processus menée par observation.Un seul centre médical universitaire aux États-Unis.La population étudiée était constituée d’adultes atteints d’IRA de stade 3 sans traitements de dialyse à leur sortie et qui avaient été mis en contact avec un fournisseur de soins primaires (FSP) dans l’établissement.Avant la mise en œuvre de l’intervention, un outil de dossier de santé électronique a été développé pour identifier les survivants à un épisode d’IRA. Le programme de l’AmTS comprenait la participation des patients pendant leur séjour à l’hôpital, une formation donnée par des infirmières formées en néphrologie avant le congé, les tests de laboratoire recommandés après la sortie de l’hôpital et un suivi structuré axé sur la santé rénale avec un pharmacien et un FSP dans les 7 à 14 jours suivant la sortie de l’hôpital. Il a été laissé à la discrétion des FSP d’aiguiller ou non leurs patients pour une évaluation en néphrologie.Des données préliminaires ont démontré qu’il était possible d’identifier, d’informer et d’assurer le suivi de la plupart des sujets d’intérêt (des survivants à un épisode d’IRA) avec ce modèle. Cette stratégie a semblé réalisable, évolutive et apte à optimiser l’expertise individuelle des membres de l’équipe multidisciplinaire.Faible taille de l’échantillon; une évaluation future du processus, des résultats cliniques et des résultats rapportés par les patients est nécessaire.Le processus de cette AmTS soutenue par une aide à la prise de décision clinique s’est avéré réalisable et a permis de combler les lacunes des modèles de transition des soins existants. Dans le contexte des soins primaires, la prestation de soins en équipe semble être un mécanisme permettant d’étendre la capacité de surveillance de la santé rénale des survivants à un épisode d’IRA.

Beta-lactam neurotoxicity is a relatively uncommon yet clinically significant adverse effect in critically ill patients. This study sought to define the incidence of neurotoxicity, derive a prediction model for beta-lactam neurotoxicity, and then validate the model in an independent cohort of critically ill adults.This retrospective cohort study evaluated critically ill patients treated with ≥ 48 h of cefepime, piperacillin/tazobactam, or meropenem. Two separate cohorts were created: a derivation cohort and a validation cohort. Patients were screened for beta-lactam neurotoxicity by using search terms and diagnosis codes, followed by clinical adjudication using a standardized adverse event scoring tool. Multivariable regression models and least absolute shrinkage and selection operator were used to identify surrogates for neurotoxicity and develop a multivariable prediction model.The overall incidence of beta-lactam neurotoxicity was 2.6% (n/N = 34/1323) in the derivation cohort and 2.1% in the validation cohort (n/N = 16/767). The final multivariable neurotoxicity assessment tool included weight, Charlson comorbidity score, age, and estimated creatinine clearance as predictors of neurotoxicity. Incidence of neurotoxicity reached 4% in those with a body mass index more than 30 kg/mIn this single center cohort of critically ill patients, beta-lactam neurotoxicity was demonstrated less frequently than previously reported. We identified obesity as a novel risk factor for the development of neurotoxicity. The prediction model needs to be further refined before it can be used in clinical practice as a tool to avoid drug-related harm.

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

BACKGROUND: Chronic tubulointerstitial injury on kidney biopsy is usually quantified by the percentage of cortex with interstitial fibrosis/tubular atrophy (IF/TA). Whether other patterns of IF/TA or inflammation in the tubulointerstitium have prognostic importance beyond percentage IF/TA is unclear. METHODS: We obtained, stained, and digitally scanned full cortical thickness wedge sections of renal parenchyma from patients who underwent a radical nephrectomy for a tumor over 2000–2015, and morphometrically analyzed the tubulointerstitium of the cortex for percentage IF/TA, IF/TA density (foci per mm(2) cortex), percentage subcapsular IF/TA, striped IF/TA, percentage inflammation (both within and outside IF/TA regions), and percentage subcapsular inflammation. Patients were followed with visits every 6–12 months. Progressive CKD was defined as dialysis, kidney transplantation, or 40% decline from the postnephrectomy eGFR. Cox models assessed the risk of CKD or noncancer mortality with morphometric measures of tubulointerstitial injury after adjustment for the percentage IF/TA and clinical characteristics. RESULTS: Among 936 patients (mean age, 64 years; postnephrectomy baseline eGFR, 48 ml/min per 1.73m(2)), 117 progressive CKD events and 183 noncancer deaths occurred over a median 6.4 years. Higher IF/TA density predicted both progressive CKD and noncancer mortality after adjustment for percentage IF/TA and predicted progressive CKD after further adjustment for clinical characteristics. Independent of percentage IF/TA, age, and sex, higher IF/TA density correlated with lower eGFR, smaller nonsclerosed glomeruli, more global glomerulosclerosis, and smaller total cortical volume. CONCLUSIONS: Higher density of IF/TA foci (a more scattered pattern with more and smaller foci) predicts higher risk of progressive CKD after radical nephrectomy compared with the same percentage of IF/TA but with fewer and larger foci.

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

INTRODUCTION AND OBJECTIVE:American Urologic Association guidelines prioritize nephron-sparing in patients with pre-existing chronic kidney disease (CKD). However, there have been few studies direc...

IMPORTANCE: Using the same level of estimated glomerular filtration rate (eGFR) to define chronic kidney disease (CKD) regardless of patient age may classify many elderly people with a normal physiological age-related eGFR decline as having a disease. OBJECTIVE: To compare the outcomes associated with CKD as defined by a fixed vs an age-adapted eGFR threshold. DESIGN, SETTING, AND PARTICIPANTS: This population-based cohort study was conducted in Alberta, Canada and used linked administrative and laboratory data from adults with incident CKD from April 1, 2009, to March 31, 2017, defined by a sustained reduction in eGFR for longer than 3 months below a fixed or an age-adapted eGFR threshold. Non-CKD controls were defined as being 65 years or older with a sustained eGFR of 60 to 89 mL/min/1.73 m(2) for longer than 3 months and normal/mild albuminuria. The follow-up ended on March 31, 2019. The data were analyzed from February to April 2020. EXPOSURES: A fixed eGFR threshold of 60 vs thresholds of 75, 60, and 45 mL/min/1.73 m(2) for age younger than 40, 40 to 64, and 65 years or older, respectively. MAIN OUTCOMES AND MEASURES: Competing risks of kidney failure (kidney replacement initiation or sustained eGFR 3 months) and death without kidney failure. RESULTS: The fixed and age-adapted CKD cohorts included 127 132 (69 546 women [54.7%], 57 586 men [45.3%]) and 81 209 adults (44 582 women [54.9%], 36 627 men [45.1%]), respectively (537 vs 343 new cases per 100 000 person-years). The fixed-threshold cohort had lower risks of kidney failure (1.7% vs 3.0% at 5 years) and death (21.9% vs 25.4%) than the age-adapted cohort. A total of 53 906 adults were included in both cohorts. Of the individuals included in the fixed-threshold cohort only (n = 72 703), 54 342 (75%) were 65 years or older and had baseline eGFR of 45 to 59 mL/min/1.73 m(2) with normal/mild albuminuria. The 5-year risks of kidney failure and death among these elderly people were similar to those of non-CKD controls, with a risk of kidney failure of 0.12% or less in both groups across all age categories and a risk of death at 69, 122, 279, and 935 times higher than the risk of kidney failure for 65 to 69, 70 to 74, 75 to 79, and 80 years or older, respectively. CONCLUSIONS AND RELEVANCE: This cohort study of adults with CKD suggests that the current criteria for CKD that use the same eGFR threshold for all ages may result in overestimation of the CKD burden in an aging population, overdiagnosis, and unnecessary interventions in many elderly people who have age-related loss of eGFR.

Objectives This study sought to characterize urinary and plasma C-type natriuretic peptide (CNP) in acute decompensated heart failure (ADHF) to define their relationship with clinical variables and to determine whether urinary and plasma CNP together add prognostic value. Background CNP is a protective hormone that is synthesized in the kidney and endothelium and possesses antiremodeling properties. Urinary and plasma CNP levels are elevated in pathophysiological conditions; however, their regulation and prognostic value in heart failure (HF) is unclear. Methods Urinary and plasma CNP were measured in 109 healthy subjects and 208 patients with ADHF; the 95th percentile of CNP values from healthy subjects established the normal contemporary cutoffs. Patients with ADHF were stratified based on urinary and plasma CNP levels for clinical characterization and the assessment of risk for adverse outcomes. Results There was no significant correlation between urinary and plasma CNP in both cohorts. Urinary and plasma CNP were significantly elevated in patients with ADHF, and both increased with disease severity and were positively correlated with plasma N-terminal pro–B-type natriuretic peptide (NT-proBNP). Of the patients with ADHF, 23% had elevations in both urinary and plasma CNP, whereas 24% had normal CNP levels. During a median follow-up of 3 years, patients with elevated urinary and plasma CNP had a significantly higher risk of rehospitalization and/or death (HR: 1.79; P = 0.03) and rehospitalization (HR: 2.16; P = 0.01) after adjusting for age, sex, left ventricular ejection fraction, renal function, and plasma NT-proBNP. The C-statistic and integrated discrimination analyses further supported that the addition of urinary and plasma CNP to established risk models improved the prediction of adverse outcomes in patients with ADHF. Conclusions Urinary and plasma CNP are differentially regulated in ADHF, and elevations in both provided independent prognostic value for predicting adverse outcomes.

Item does not contain fulltext Current criteria for the diagnosis of CKD in adults include persistent signs of kidney damage, such as increased urine albumin-to-creatinine ratio or a GFR below the threshold of 60 ml/min per 1.73 m(2) This threshold has important caveats because it does not separate kidney disease from kidney aging, and therefore does not hold for all ages. In an extensive review of the literature, we found that GFR declines with healthy aging without any overt signs of compensation (such as elevated single-nephron GFR) or kidney damage. Older living kidney donors, who are carefully selected based on good health, have a lower predonation GFR compared with younger donors. Furthermore, the results from the large meta-analyses conducted by the CKD Prognosis Consortium and from numerous other studies indicate that the GFR threshold above which the risk of mortality is increased is not consistent across all ages. Among younger persons, mortality is increased at GFR

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

Matrix-Gla-protein (MGP) is an inhibitor of vascular calcification. Its dephosphorylated and uncarboxylated inactive form, dpucMGP, is a marker of vitamin K status and of cardio-vascular outcomes in chronic kidney disease. We hypothesized that higher serum dpucMGP would be a biomarker of kidney stone disease. We measured serum dpucMGP in incident symptomatic kidney stone-formers and non-stone formers at a baseline visit. Symptomatic stone recurrence was assessed in the stones formers over a 5-year period. The association of dpucMGP with incident or recurrent kidney stones was assessed with and without adjustment for clinical, blood, and urine characteristics. There was no significant difference in serum dpucMGP level between 498 stone formers and 395 non-stone former (510 vs 501 pmol/L; p = 0.66). In a multivariable model adjusting for clinical, blood and urine chemistries, higher MGP was associated with lower risk of stone formation (OR = 0.674, 95% CI 0.522–0.870), contrary to previous reports. Among 375 stone formers with 5 years of follow-up, 79 (21%) had symptomatic recurrence. No difference in serum dpucMGP was evident in recurrent versus non-recurrent stone-formers (482 vs 502 pmol/L; p = 0.26). Serum dpucMGP was correlated with cystatin C levels in non stone-formers, incident stone-formers and recurrent stone-formers (r > 0.3, p

BACKGROUND: The medium- to long-term outcomes of living kidney donors with hypertension compared to normotensive donors are not well understood, especially with the recent changes in hypertension guidelines. METHODS: We studied a cohort of 950 living kidney donors using different definitions of hypertension based on either ≥140/90 or ≥130/80 mmHg thresholds and based on either office or ambulatory blood pressure readings. Microstructural features on kidney biopsy at the time of donation were compared using different definitions of hypertension. RESULTS: After adjusting for years of follow-up, age, sex, and baseline eGFR, hypertension (by any definition) did not significantly predict an eGFR < 45 ml/min/1.73 m(2) at a median follow-up of 10 years postdonation, though there was a borderline association with ambulatory blood pressure ≥ 130/80 mmHg predicting a 40% decline in eGFR (OR = 1.53, 1.00–2.36; p = .051). Proteinuria was predicted by office blood pressure ≥ 140/90 mmHg and by nondipper profile on nocturnal ambulatory blood pressure measurements. At the time of donation, larger glomeruli and arterial hyalinosis on biopsy were associated with hypertension defined by either ≥140/90 or ≥130/80 mmHg (by office or ambulatory measurements). Nocturnal nondipper status was associated with larger glomeruli size but not arteriolar hyalinosis when compared to dippers. CONCLUSIONS: In programs that accept donors with controlled hypertension, various definitions of hypertension are associated with histological findings in the donated kidney, but none predict a clinically significant decline in kidney function 10 years after donation. These data support allowing healthy individuals with controlled hypertension to donate a kidney. However, donors with office hypertension (≥140/90 mmHg) and nondippers (regardless of hypertension status) are at greater long-term risk for proteinuria, and particularly for these donors, longer follow-up is warranted.

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.

The use of the kidney function biomarker cystatin C (cysC) can improve the accuracy of vancomycin dosing for target trough attainment in nonobese patients. It is unknown whether cysC can also improve vancomycin target trough attainment in overweight and obese patients. We conducted a retrospective observational study of overweight or obese hospitalized adults with stable renal function administered intravenous vancomycin between January 2011 and July 2019. Linear regression models were used to predict initial steady-state vancomycin troughs using several factors, including various cysC- and serum creatinine (SCr)-based estimates of kidney function. We compared the predicted proportion of patients within the target trough range (10 to 20 mg/liter) using the derived models to that observed from usual care. Of the 200 included patients, the mean trough level was 15 ± 6.3 mg/liter. The optimal model to predict the initial trough included both cysC and SCr (R(2) = 0.48) rather than either biomarker alone. This model predicted that 79% (95% confidence interval [CI], 73% to 85%) of troughs could be between 10 and 20 mg/liter compared to the 62% observed in clinical practice (P

BACKGROUND: Single-nephron dynamics in progressive IgA nephropathy (IgAN) have not been studied. We applied novel methodology to explore single-nephron parameters in IgAN. METHODS: Nonglobally sclerotic glomeruli (NSG) and globally sclerotic glomeruli (GSG) per kidney were estimated using cortical volume assessment via unenhanced computed tomography and biopsy-based stereology. Estimated single-nephron GFR (eSNGFR) and single-nephron urine protein excretion (SNUPE) were calculated by dividing eGFR and UPE by the number of NSG. Associations with CKD stage and clinicopathologic findings were cross-sectionally investigated. RESULTS: This study included 245 patients with IgAN (mean age 43 years, 62% male, 45% on renin-angiotensin aldosterone system [RAAS] inhibitors prebiopsy) evaluated at kidney biopsy. CKD stages were 10% CKD1, 43% CKD2, 19% CKD3a, 14% CKD3b, and 14% CKD4–5. With advancing CKD stage, NSG decreased from mean 992,000 to 300,000 per kidney, whereas GSG increased from median 64,000 to 202,000 per kidney. In multivariable models, advancing CKD stage associated with lower numbers of NSG, higher numbers of GSG, and lower numbers of GSG + NSG, indicating potential resorption of sclerosed glomeruli. In contrast to the higher mean glomerular volume and markedly elevated SNUPE in advanced CKD, the eSNGFR was largely unaffected by CKD stage. Lower SNGFR associated with Oxford scores for endocapillary hypercellularity and crescents, whereas higher SNUPE associated with segmental glomerulosclerosis and tubulointerstitial scarring. CONCLUSIONS: SNUPE emerged as a sensitive biomarker of advancing IgAN. The failure of eSNGFR to increase in response to reduced number of functioning nephrons suggests limited capacity for compensatory hyperfiltration by diseased glomeruli with intrinsic lesions.

Background The Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) creatinine equation is routinely used to assess renal function but exhibits varying accuracy depending on patient characteristics and clinical presentation. The overall aim of the present study was to assess if and to what extent glomerular filtration rate (GFR) estimation based on creatinine can be improved. Methods In a cross-sectional analysis covering the years 2003–17, CKD-EPI was validated against measured GFR (mGFR; using various tracer methods) in patients with high likelihood of chronic kidney disease (CKD; five CKD cohorts, n = 8365) and in patients with low likelihood of CKD (six community cohorts, n = 6759). Comparisons were made with the Lund–Malmö revised equation (LMR) and the Full Age Spectrum equation. Results 7In patients aged 18–39 years old, CKD-EPI overestimated GFR with 5.0–16 mL/min/1.73 m2 in median in both cohort types at mGFR levels Conclusions None of the evaluated equations made optimal use of available data. Prospects for improved GFR estimation procedures based on creatinine exist, particularly in young adults and in settings where patients with suspected or manifest CKD are investigated.

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 Results Total EVs and EVs from different types of glomerular and renal tubular cells (11/13 markers) were significantly (Q Conclusions These results imply activation of distinct renal tubular and interstitial cell populations and processes associated with KS and NC, and suggest specific populations of urinary EVs and proteins are potential biomarkers to assess the pathogenic mechanisms between KS versus NC among PH1 patients.

The incidence and prevalence of kidney stones have increased over the past four decades. However, the diagnosis of 'kidney stone' can range from an incidental asymptomatic finding of limited clinical significance to multiple painful episodes of ureteral obstruction with eventual kidney failure. Some general strategies may be useful to prevent the recurrence of kidney stones. In particular, greater attention to kidney stone classification, approaches to assessing the risk of recurrence and individualized prevention strategies may improve the clinical care of stone formers. Although there have been some advances in approaches to predicting the recurrence of kidney stones, notable challenges remain. Studies of kidney stone prevalence, incidence and recurrence have reported inconsistent findings, in part because of the lack of a standardized stone classification system. A kidney stone classification system based on practical and clinically useful measures of stone disease may help to improve both the study and clinical care of stone formers. Any future kidney stone classification system should be aimed at distinguishing asymptomatic from symptomatic stones, clinically diagnosed symptomatic stone episodes from self-reported symptomatic stone episodes, symptomatic stone episodes that are confirmed from those that are suspected, symptomatic recurrence from radiographic recurrence (that is, with radiographic evidence of a new stone, stone growth or stone disappearance from presumed passage) and determine stone composition based on mutually exclusive categories.

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.

Drug-associated acute interstitial nephritis (AIN) is characterized by acute or subacute loss of kidney function, interstitial infiltrates, edema, and tubulitis on kidney biopsy, with a relative sparing of the glomerulus and vasculature (1). Estimates indicate that AIN is the primary finding in 2%–5% of all native kidney biopsies. In those biopsied for acute kidney dysfunction, the frequency of AIN is closer to 10%–30%, although the true burden of AIN likely remains underestimated (1). Due to procedural risk, biopsies are often deferred in favor of empirical discontinuation of the suspected offending agent. Several AIN etiologies have been identified, but the majority of cases (60%–70%) have been linked to drugs and toxins. Drug-associated AIN is thought to be a cell-mediated immune response, akin to a type 4 (delayed-type) hypersensitivity reaction (2). Mechanistic explanations for AIN include that drugs could act as haptens to modify the endogenous response to native renal proteins or induce an autoimmune reaction to the tubular basement membrane through molecular mimicry. Drugs could also rarely lead to systemic immune activation that contributes to deposition or sequestration of immune complexes in the renal interstitium (2,3). As early as 7 days after drug exposure, the early inflammatory lesions in AIN can begin to evolve into irreversible interstitial fibrosis. This likely explains why, even with the best available management, only 40%–50% of patients with AIN experience complete renal recovery (4). As more and diverse cases of drug-associated AIN have been reported, it is apparent that the “classic triad” of extrarenal manifestations—which include fever, rash, and eosinophilia—only occur in about 10% of patients (5,6). Rather, drug-associated AIN has a highly variable presentation. In 133 cases of biopsy-confirmed AIN (95 of which were drug-related), fever, rash, and eosinophilia individually occurred in 20%–23% of patients. Microscopic hematuria, sterile pyuria, and …

Background Reliable and valid tools to screen for malnutrition in the intensive care unit (ICU) remain elusive. The sarcopenia index (SI) [(serum creatinine/serum cystatin C) × 100], could be an inexpensive, objective tool to predict malnutrition. We evaluated the SI as a screening tool for malnutrition in the ICU and compared it with the modified-NUTRIC score. Materials and methods This was a historical cohort study of ICU patients with stable kidney function admitted to Mayo Clinic ICUs between 2008 and 2015. Malnutrition was defined by the Subjective Global Assessment. Diagnostic performance was evaluated with the area under the receiver operating characteristic curve (AUC) and multivariable logistic regression. Results Of the 398 included patients, 181 (45%) had malnutrition, with 34 (9%) scored as severely malnourished. The SI was significantly lower in malnourished patients than in well-nourished patients (64 ± 27 vs 72 ± 25; P = 0.002), and reductions in SI corresponded to increased malnutrition severity (P = 0.001). As a screening tool, the SI was an indicator of malnutrition risk (AUC 0.61) and performed slightly better than the more complex modified-NUTRIC score (AUC = 0.57). SI cutoffs of 101 and 43 had >90% sensitivity and >90% specificity, respectively, for the prediction of malnutrition. Patients with a low SI (≤43) had a significantly higher risk of mortality (HR = 2.61, 95% CI 1.06-6.48, P = 0.038). Conclusion The frequency of malnutrition was high in this critically ill population, and it was associated with a poor prognosis. The SI could be used to assess nutrition risk in ICU patients.

Objective Patients receiving dialysis are at increased risk for lower extremity amputations (LEAs) and postoperative morbidity. Limited studies have examined differences in 30-day outcomes of mortality and health care use after amputation or the preoperative factors that relate to worsened outcomes in dialysis patients. Our objective was to examine dialysis dependency and other preoperative factors associated with readmission or death after LEA. Methods A retrospective cohort study was conducted of dialysis-dependent and nondialysis patients undergoing major LEA in the 2012 to 2013 American College of Surgeons National Surgical Quality Improvement Program. Primary outcomes included death and hospital readmission within 30 days of amputation. Results Of 6468 patients, 1166 (18%) were dialysis dependent. The dialysis cohort had more blacks (39% vs 23%), diabetes (76% vs 58%), below-knee amputations (62% vs 55%), and in-hospital deaths (8% vs 3%; all P Conclusions Readmission or death after amputation is increased among dialysis patients. Predicting which dialysis patients are at highest risk for death is feasible, whereas predicting which will require readmission is less so. Risk factor identification may improve risk stratification, inform reimbursement policies, and allow targeted interventions to improve outcomes.

Introduction It is unknown whether patients receiving dialysis have a higher morbidity and mortality risk after hip fracture repair conferred by their kidney failure or by the high comorbidity burden often present. Methods We examined associations of dialysis dependency with postoperative complications, death, and readmission in a matched cohort study of U.S. patients undergoing hip fracture repair, from January 2010 to December 2013, in the American College of Surgeons National Surgical Quality Improvement Program. Matching included sex, age, race, diabetes mellitus, operation year, primary surgery type, and anesthesia technique. Results Among 22,621 patients, 377 dialysis-dependent patients were matched to 1508 nondialysis patients. Median age was 78 years (interquartile range = 68−85) years, 56% were men, 70% were white, 43% had diabetes, and 47% underwent fracture fixation under mostly (80%) general anesthesia. Dialysis-dependent patients had higher physical status classification, had more heart failure and hypoalbuminemia, and were less often smokers. After adjustment, a greater risk of prolonged postoperative stays beyond 7 days (odds ratio [OR] = 1.43, 95% confidence interval [CI] = 1.09−1.89), higher in-hospital mortality (OR = 3.13, CI = 1.72−5.7), and 30-day death (OR = 2.29, CI = 1.51−3.48) but not 30-day readmission (P = 0.09) was observed with dialysis dependency. Adjusted analyses in the original cohort (n = 22,621) were similar: the dialysis group had greater risk of prolonged postoperative stay (OR = 1.77, CI = 1.42−2.21), in-hospital mortality (OR = 2.65, CI = 1.74−4.05), and 30-day death (OR = 2.03, CI = 1.48−2.80) and 30-day readmission (OR = 1.62, CI = 1.66−2.26). Conclusion Dialysis dependency is associated with an increased risk of death and postoperative complications after hip fracture repair. These findings have implications for case-mix adjustment and quality metrics.

Routine preventive cancer screening is not recommended for patients with end-stage renal disease (ESRD)1 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., Highlights • Dialysis patients have relatively high rates of cancer screening. • Patients seen in primary care were more likely to get breast and colon ca screening. • Half of women over age 65 received breast cancer screening within two years.

Background Glomerular volume increases when demand exceeds nephron supply, which may lead to glomerulosclerosis. It is unclear if determinants of glomerular volume are consistent between populations that differ by severity of comorbidities.Methods We studied kidney biopsy specimens from living kidney donors (n=2453) and patients who underwent radical nephrectomy for a renal tumor (n=780). We scanned specimen sections into high-resolution digital images, manually traced glomerular profiles, and calculated mean glomerular volumes using the Weibel-Gomez stereologic formula (separately for nonsclerosed glomeruli and globally sclerosed glomeruli). We then assessed the relationship of glomerular volume with age, clinical characteristics, and nephrosclerosis on biopsy specimen.Results Compared with kidney donors, patients with tumors were older and more frequently men, obese, diabetic, or hypertensive, had more glomerulosclerosis and interstitial fibrosis on biopsy specimen, and had 12% larger nonsclerosed glomeruli (P 25%, and interstitial fibrosis >25% also associated with larger nonsclerosed glomeruli. Independent clinical predictors of larger nonsclerotic glomeruli were family history of ESRD, male sex, taller height, obesity, diabetes, and proteinuria. After adjustment for these characteristics, nonsclerotic glomerular volume did not differ between populations and was stable up to age 75 years, after which it decreased with age. Many of these findings were also evident with globally sclerotic glomerular volume.Conclusions Characteristics associated with glomerular volume are consistent between patient populations with low and high levels of comorbidity.