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This research explored the intact nephron hypothesis (INH) as a model for metformin dosing in patients with chronic kidney disease (CKD). The INH assumes that glomerular filtration rate (GFR) will account for all kidney drug handling even for drugs eliminated by tubular secretion like metformin. We conducted two studies: (1) a regression analysis to explore the relationship between metformin clearance and eGFR metrics, and (2) a joint population pharmacokinetic analysis to test the relationship between metformin renal clearance and gentamicin clearance. The relationship between metformin renal clearance and eGFR metrics and gentamicin clearance was found to be linear, suggesting that a proportional dose reduction based on GFR in patients with CKD is reasonable.

Purpose To investigate the association between urinary complement proteins and renal outcome in biopsy-proven diabetic nephropathy (DN). Methods Untargeted proteomic and Kyoto Encyclopedia of Genes and Genomes (KEGG) functional analyses and targeted proteomic analysis using parallel reaction-monitoring (PRM)-mass spectrometry was performed to determine the abundance of urinary complement proteins in healthy controls, type 2 diabetes mellitus (T2DM) patients, and patients with T2DM and biopsy-proven DN. The abundance of each urinary complement protein was individually included in Cox proportional hazards models for predicting progression to end-stage renal disease (ESRD). Results Untargeted proteomic and functional analysis using the KEGG showed that differentially expressed urinary proteins were primarily associated with the complement and coagulation cascades. Subsequent urinary complement proteins quantification using PRM showed that urinary abundances of C3, C9, and complement factor H (CFAH) correlated negatively with annual estimated glomerular filtration rate (eGFR) decline, while urinary abundances of C5, decay-accelerating factor (DAF), and CD59 correlated positively with annual rate of eGFR decline. Furthermore, higher urinary abundance of CFAH and lower urinary abundance of DAF were independently associated with greater risk of progression to ESRD. Urinary abundance of CFAH and DAF had a larger area under the curve (AUC) than that of eGFR, proteinuria, or any pathological parameter. Moreover, the model that included CFAH or DAF had a larger AUC than that with only clinical or pathological parameters. Conclusion Urinary abundance of complement proteins was significantly associated with ESRD in patients with T2DM and biopsy-proven DN, indicating that therapeutically targeting the complement pathway may alleviate progression of DN.

Determination of renal function is particularly important when prescribing antibiotics to elderly patients. This study aims to determine the correlation between estimated creatinine clearance and the estimated glomerular filtration rate, for a hospitalized population of very elderly patients, and to audit antibiotic prescribing errors.Retrospective cohort study of all patients ≥ 80 years hospitalized with antibiotic. Creatinine clearance was calculated using Cockcroft-Gault equation and estimated glomerular filtration rate by Modification of Diet in Renal Disease Study and Chronic Kidney Disease Epidemiology Collaboration equations. Dosing errors were determined through adjustment of daily define dose to renal function.The study included 589 patients. The correlation of Cockcroft-Gault with Modification of Diet in Renal Disease and Chronic Kidney Disease Epidemiology Collaboration was r = 0.98 and 0.96 for the minimum serum creatinine, and 0.97 and 0.93 for the maximum serum creatinine. Based on Cockcroft-Gault, there were errors in the daily defined dose in 45% in the minimum serum creatinine, and 52% in the maximum serum creatinine day. There was a discrepancy in the recording of errors of 14% to 16% when Cockcroft-Gault was compared with Modification of Diet in Renal Disease and Chronic Kidney Disease Epidemiology Collaboration.There was a good correlation of Cockcroft-Gault with the estimated glomerular filtration rate by Modification of Diet in Renal Disease or Chronic Kidney Disease Epidemiology Collaboration. Regardless of the equation used to estimate renal function there was a high rate of antibiotic dosing errors documented in this population.This study supports the maintenance of the Cockcroft-Gault equation for drug dosing in the very elderly population. Further studies are needed to investigate underlying causes of prescribing errors.Introdução: A determinação da função renal é particularmente importante na prescrição de antibióticos em doentes idosos. O objetivo deste estudo é correlacionar a clearance de creatinina com a taxa de filtração glomerular estimada, numa população hospitalizada de doentes muito idosos, e auditar os erros de prescrição antibiótica. Material e Métodos: Coorte retrospetivo de todos os doentes ≥ 80 anos hospitalizados com antibioterapia prescrita. A clearance de creatinina foi calculada através da equação Cockcroft-Gault, e a filtração glomerular estimada através das equações Modification of Diet in Renal Disease e Chronic Kidney Disease Epidemiology Collaboration. Os erros de prescrição foram determinados pelo ajuste da dose diária definida à função renal. Resultados: Foram incluídos 589 doentes. A correlação da Cockcroft-Gault com Modification of Diet in Renal Disease e Chronic Kidney Disease Epidemiology Collaboration foi r = 0,98 e 0,96 para a creatinina sérica mínima, e 0,97 e 0,93 para a creatinina sérica máxima. Com base na Cockcroft-Gault, a taxa de erro na dose diária definida foi 45% no dia da creatinina sérica mínima e 52% no dia da creatinina sérica máxima. Quando a Cockcroft-Gault foi comparada com a Modification of Diet in Renal Disease e a Chronic Kidney Disease Epidemiology Collaboration houve uma discrepância no registo de erros de 14% a 16%, respetivamente. Discussão: Verificou-se uma boa correlação entre a Cockcroft-Gault e as equações que calculam a filtração glomerular: Modification of Diet in Renal Disease ou Chronic Kidney Disease Epidemiology Collaboration. Independentemente da equação utilizada para estimar a função renal, foi documentada uma taxa elevada de erros na dose de antibióticos prescrita nesta população. Conclusão: Este estudo reforça a manutenção do uso da equação de Cockcroft-Gault para calcular a dose adequada de antibióticos na população muito idosa. Mais estudos são necessários para investigar as causas subjacentes aos erros de prescrição.

Jing Xiong,1,* Yunyun Qian,1,* Shikai Yu,1 HongWei Ji,1 Jiadela Teliewubai,1 Chen Chi,1 YuYan Lu,1 YiWu Zhou,1 XiMin Fan,1 Jue Li,2 Jacques Blacher,3 Yi Zhang,1 YaWei Xu1 1Department of Cardiology, Shanghai Tenth People’s Hospital, Tongji University School of Medicine, Shanghai, People’s Republic of China; 2The Research Institute of Clinical Epidemiology, Tongji University School of Medicine, Shanghai, People’s Republic of China; 3Paris Descartes University, AP-HP, Diagnosis and Therapeutic Center, Hôtel-Dieu, Paris, France*These authors contributed equally to this workCorrespondence: Yi Zhang; Yawei XuDepartment of Cardiology, Shanghai Tenth People’s Hospital, Tongji University School of Medicine, 301 Yanchang Road, Shanghai, 200072, ChinaTel +86-21-66308182Fax +86-21-66301051Email yizshcn@gmail.com; xuyawei@tongji.edu.cnObjective: To investigate the relationship between asymptomatic target organ damage (TOD) and different somatotypes in a population of elderly from Chinese community-dwelling.Methods: A total of 2098 Chinese senior residents from northern Shanghai older than 65 years were recruited in the research. The following somatotype parameters were recorded and analyzed: body mass index, waist circumference, hip circumference, and waist-hip ratio were recorded and calculated. Asymptomatic TOD, including urine albumin/creatinine ratio, estimated glomerular filtration rate (eGFR), intima-media thickness (IMT), left ventricular mass index (LVMI), left ventricular diastolic function, and carotid-femoral pulse wave velocity (PWV) was recorded using the MyLab30 Gold CV system and SphygmoCor.Results: Of all 2098 residents, 817 (38.9%) were overweight and 289 (13.8%) were obese. All somatotype measures were significantly correlated with TOD parameters (p< 0.05). After adjustment for age and male gender, in total population, LVMI (p< 0.001), cardiac diastolic function (E/Ea, p< 0.001), PWV (p< 0.001), eGFR (p=0.03), and urine albumin/creatinine ratio (p< 0.001) changed gradually and significantly correlated with increasing BMI values. Obesity and overweight were independently related to the incidence of LVH, LVDD, artery stiffness, carotid arterial plaque, and microalbuminuria.Conclusion: The incidence of asymptomatic TOD was significantly correlated with overweight and obesity, especially in women, whereas the underweight may favor in the prevention of TOD.Keywords: Chinese elderly cardiovascular risk

Aim Predicting progression in diabetic kidney disease (DKD) is critical to improving outcomes. We sought to develop/validate a machine-learned, prognostic risk score (KidneyIntelX™) combining electronic health records (EHR) and biomarkers. Methods This is an observational cohort study of patients with prevalent DKD/banked plasma from two EHR-linked biobanks. A random forest model was trained, and performance (AUC, positive and negative predictive values [PPV/NPV], and net reclassification index [NRI]) was compared with that of a clinical model and Kidney Disease: Improving Global Outcomes (KDIGO) categories for predicting a composite outcome of eGFR decline of ≥5 ml/min per year, ≥40% sustained decline, or kidney failure within 5 years. Results In 1146 patients, the median age was 63 years, 51% were female, the baseline eGFR was 54 ml min−1 [1.73 m]−2, the urine albumin to creatinine ratio (uACR) was 6.9 mg/mmol, follow-up was 4.3 years and 21% had the composite endpoint. On cross-validation in derivation (n = 686), KidneyIntelX had an AUC of 0.77 (95% CI 0.74, 0.79). In validation (n = 460), the AUC was 0.77 (95% CI 0.76, 0.79). By comparison, the AUC for the clinical model was 0.62 (95% CI 0.61, 0.63) in derivation and 0.61 (95% CI 0.60, 0.63) in validation. Using derivation cut-offs, KidneyIntelX stratified 46%, 37% and 17% of the validation cohort into low-, intermediate- and high-risk groups for the composite kidney endpoint, respectively. The PPV for progressive decline in kidney function in the high-risk group was 61% for KidneyIntelX vs 40% for the highest risk strata by KDIGO categorisation (p event for the high-risk group was 41% (p Conclusions KidneyIntelX improved prediction of kidney outcomes over KDIGO and clinical models in individuals with early stages of DKD. Graphical abstract

The CKD-EPI creatinine-based estimation equation for glomerular filtration rate (GFR) cannot be used in children, overestimates GFR in young adults, and its combination with the KDIGO recommended pediatric CKiD (Schwartz bedside) equation causes implausible increases in estimated GFR when switching from pediatric to adult care. By establishing sex-specific creatinine growth curves for children and young adults, creatinine levels of children and young adults below age 40 years were adjusted with 40 as assigned age and applied in the CKD-EPI equation. Validation was performed in 4005 children (2-17 years) and 3309 young adults (18-39 years) using metrics based on bias, precision, and accuracy including percentage of estimates within 30% (P30) of measured GFR (mGFR). Comparisons were made with the CKiD and Schwartz-Lyon equations in children. CKD-EPI with age-adjusted creatinine instead of actual age and creatinine led to extensive improvements in bias, precision, and accuracy at all ages, in both sexes and at all levels of mGFR. At mGFR below and above 75 mL/min/1.73m2, the P30 increased from 12% to 75% and 33% to 88% in children, respectively, and from 56% to 73% and 83% to 92% in young adults, respectively. In children adjusted CKD-EPI was more accurate than CKiD, especially above mGFR 75 mL/min/1.73m2 (P30 88% vs. 82%), while Schwartz-Lyon was more accurate than adjusted CKD-EPI at mGFR below 75 mL/min/1.73m2 (P30 81% vs. 75%). Thus, the proposed strategy based on age-adjusted creatinine in children and young adults makes the CKD-EPI equation applicable across the full spectrum of age and kidney function. ispartof: KIDNEY INTERNATIONAL vol:99 issue:4 pages:940-947 ispartof: location:United States status: published

Advanced age is a high-risk factor for exacerbation of coronavirus disease 2019 (COVID-19), which causes a high rate of mortality. Therefore, it is important to strengthen the warning and monitoring of severe patients, and early identify the severe and critically severe types in time in the clinical treatment of COVID-19. Moreover, it is necessary to pay attention to the adverse reactions and damage to vital target organs caused by treatment drugs. This study reports the successful experience of diagnosis and treatment of an older patient with COVID-19 accompanied by progressive renal impairment, and pertinent literature was reviewed to help clinicians raise awareness of the disease.

Objective: To report the case of a pediatric patient with bilateral hydronephrosis due to vesicoureteral junction obstruction (VUJO) that was treated non-surgically and to discuss the approach of this anomaly. Case Description: A 25-month-old boy was referred without complaints for consultation due to prenatal ultrasound showing kidneys with cysts. He was under antibiotic prophylaxis. No family history of kidney disease and/or inherited disorders was reported. Renal ultrasound (RUS) at 2 days of life showed bilateral hydronephrosis, thus ruling out the possibility of kidney cystic disease. Dynamic renal scintigraphy (DTPA) showed marked retention of the marker in the pyelocaliceal system bilaterally, with little response to diuretic drug. He was maintained under antibiotic prophylaxis, when a new RUS showed bilateral ureteral dilatation, abrupt stenosis in the ureterovesical transition region (0.2 cm caliber), moderate bilateral hydronephrosis, and slight renal cortical thickness, confirming the diagnosis of VUJO. At 2 years and 10 months of age, DTPA showed hydronephrosis and ureteral stasis in both kidneys secondary to stenosis at the vesicoureteral junction (VUJ) level, with preservation of kidney function and slow degree of emptying. We opted for a non-surgical approach. RUS at 10 years of age showed significant improvement of all parameters, with ureteral transverse diameter of 9 mm, preserved VUJ, and age-appropriate bilateral kidney development. Comments: VUJO is a major cause of prenatal hydronephrosis and can trigger a deterioration of kidney function. Its treatment is still controversial but should take into account the importance of clinical follow-up and serial imaging evaluation. Resumo Objetivo: Relatar o caso de um paciente pediátrico com hidronefrose bilateral devido à obstrução da junção vesicoureteral (OJVU) que foi tratado não cirurgicamente e discutir a abordagem desta anomalia. Descrição do caso: Um menino de 25 meses de idade foi encaminhado sem queixas para consulta devido à ultrassonografia pré-natal que mostrou rins com cistos. Ele estava sob profilaxia antibiótica. Nenhum histórico familiar de doença renal e/ou distúrbios hereditários foi relatado. A ultrassonografia renal (USR) aos 2 dias de vida mostrou hidronefrose bilateral, descartando assim a possibilidade de doença renal cística. A cintilografia renal dinâmica (DTPA) mostrou uma retenção acentuada do marcador no sistema pielocalicial bilateralmente, com pouca resposta ao diurético. O paciente foi mantido em profilaxia antibiótica, quando uma nova USR apresentou dilatação ureteral bilateral, estenose abrupta na região de transição ureterovesical (calibre 0,2 cm), hidronefrose bilateral moderada e leve espessura cortical renal, confirmando o diagnóstico de OJVU. Aos 2 anos e 10 meses de idade, a DTPA mostrou hidronefrose e estase ureteral em ambos os rins secundárias à estenose no nível da junção vesicoureteral (JVU), com preservação da função renal e grau lento de esvaziamento. Optamos por uma abordagem não cirúrgica. A USR aos 10 anos de idade mostrou melhora significativa de todos os parâmetros, com diâmetro transverso ureteral de 9 mm, JVU preservada, e desenvolvimento renal bilateral adequado à idade. Comentários: A OJVU é uma das principais causas de hidronefrose pré-natal e pode desencadear uma deterioração da função renal. Seu tratamento ainda é controverso, mas deve levar em consideração a importância do acompanhamento clínico e da avaliação seriada por imagem.

Chemotherapeutic agents require precise dosing to ensure optimal efficacy and minimize complications. For those agents which are removed from the body by the kidney, accurate knowledge of glomerular filtration rate (GFR) is critical. In addition, GFR needs to be determined rapidly, easily and, if possible, with little additional cost. The ability to easily measure GFR also allows for rapid detection of nephrotoxicity. Current methodologies include direct clearance measurement of an indicator substance or estimation of creatinine clearance or GFR through regression equations that use a serum marker such as creatinine or cystatin C. These methodologies all have shortfalls and limitations some of which are specific to the cancer patient. Newer methodologies that directly measure GFR are in clinical trials and offer the ability to rapidly and non-invasively provide accurate estimates of drug clearance as well as detection of nephrotoxicity. These methods offer the opportunity to refine drug dosing and improve outcomes.

Monitoring renal function is a vital part of kidney research involving rats. The laborious measurement of glomerular filtration rate (GFR) with administration of exogenous filtration markers does not easily allow serial measurements. Using an in-house database of inulin clearances, we developed and validated a plasma creatinine- and plasma urea-based equation to estimate GFR in a large cohort of male rats [development cohort n = 325, R2 = 0.816, percentage of predictions that fell within 30% of the true value (P30) = 76%] that had high accuracy in the validation cohort (n = 116 rats, R2 = 0.935, P30 = 79%). The equation was less accurate in rats with nonsteady-state creatinine, in which the equation should therefore not be used. In conclusion, applying this equation facilitates easy and repeatable estimates of GFR in rats. NEW & NOTEWORTHY This is the first equation, that we know of, which estimates glomerular filtration rate in rats based on a single measurement of body weight, plasma creatinine, and plasma urea.

Objective The present study investigated the predictive value of albuminuria for contrast-induced nephropathy (CIN) non-recovery in patients undergoing percutaneous coronary intervention (PCI). Methods We retrospectively enrolled 550 consecutive patients inflicted with CIN after PCI and reassessing kidney function among 1 week–12 months between January 2012 and December 2018. Patients were stratified into three groups according to urine albumin: negative group (urine dipstick negative), trace group (urine dipstick trace) and positive group (urine dipstick ≥ 1 +). The primary outcomes were CIN non-recovery (a decrease of serum creatinine which remains ≥ 25% or 0.5 mg/dL over baseline at 1 week–12 months after PCI in patients inflicted with CIN). The odds ratio (OR) of CIN non-recovery was analyzed by logistic regression using the negative urine dipstick group as the reference group. Results Overall, 88 (16.0%) patients had trace urinary albumin, 74 (13.5%) patients had positive urinary albumin and 40 (7.3%) patients developed CIN non-recovery. Patients with positive urinary albumin had significantly higher incidence of CIN non-recovery [negative (3.4%), trace (11.4%) and positive (23.0%), respectively; P P = 0.022; positive vs negative: OR 2.99, P = 0.021). These associations were consistent in subgroups of patients stratified by CIN non-recovery risk predictors. And CIN non-recovery was associated with an increased risk of long-term mortality during a mean follow-up period of 703 days (P Conclusion Preprocedural albuminuria was associated with CIN non-recovery in patients undergoing PCI.

Background: Rapid and accurate assessment of kidney function in patients after transplantation is of utmost importance. The aim of this study was to compare the relationships of serum creatinine and serum cystatin C with an estimated glomerular filtration rate (eGFR) in kidney transplants Saudi patients after a certain period of transplantation. Materials and Methods: In this prospective study, 127 patients were categorized into three groups based on their length of survival after kidney transplantation

The benefits and risks of aspirin therapy for patients with chronic kidney disease (CKD) who have a high burden of cardiovascular events (CVE) are controversial. To examine the effects of low-dose aspirin on major clinical outcomes in patients with CKD. As a prospective observational cohort study, using propensity score matching, 531 aspirin recipients and non-recipients were paired for analysis from 2070 patients and fulfilled the inclusion criteria among 2238 patients with CKD. The primary outcome was the first occurrence of major CVE. The secondary outcomes were kidney events defined as a > 50% reduction of estimated glomerular filtration rate from baseline, doubling of serum creatinine, or onset of kidney failure with replacement therapy, the all-cause mortality, and bleeding event. The incidence of CVE was significantly greater in low-dose aspirin users than in non-users (HR 1.798; P = 0.011). A significant association between aspirin use and an increased risk of CVE was observed only in the lowest quartile of body weight (HR 4.014; P = 0.019) (Q1

Serum bilirubin, a potent endogenous antioxidant, has been associated with decreased risks of cardiovascular disease, diabetes, and kidney disease. However, the effects of serum bilirubin on kidney transplant outcomes remain undetermined. We analyzed 1628 patients who underwent kidney transplantations between 2003 and 2017. Patients were grouped into sex-specific quartiles according to mean serum bilirubin levels, 3-12 months post-transplantation. Median bilirubin levels were 0.66 mg/dL in males and 0.60 mg/dL in females. The intra-individual variability of serum bilirubin levels was low (9%). Serum bilirubin levels were inversely associated with graft loss, death-censored graft failure, and all-cause mortality, independent of renal function, donor status, and transplant characteristics. Multivariable analysis revealed that the lowest serum bilirubin quartile was associated with increased risk of graft loss (HR 2.63, 95% CI 1.67-4.16, P < 0.001), death-censored graft failure (HR 2.96, 95% CI 1.62-5.40, P < 0.001), and all-cause mortality (HR 2.07, 95% CI 1.01-4.23, P = 0.046). Patients with lower serum bilirubin were also at greater risk of late-onset rejection and exhibited consistently lower glomerular filtration rates than those with higher serum bilirubin. Serum bilirubin levels were significantly associated with transplantation outcomes, suggesting that bilirubin could represent a therapeutic target for improving long-term transplant outcomes.

Purpose Patient factors such as age and glomerular filtration rate (GFR), have been implicated as causes for poor reproducibility of differential renal function (DRF) estimates on 99mTc-mercaptoacetyltriglycine (99mTc-MAG3) renography. This study aims to investigate factors associated with the reproducibility of DRF measurements. Methods The association between age, GFR and imaged derived image characteristics and reproducibility of repeated DRF estimates calculated using the area under the curve method and the Rutland Patlak method was analysed for cohort 1 (n = 127). The association between these variables and reproducibility of DRF was tested with univariate linear regression. The univariate linear regression results were used to plan the multiple linear regression combinations. The associations between variables identified and reproducibility of DRF values were then tested in a second cohort (n = 227). Results The R2 values for goodness-to-fit for the multiple regression models ranged from 0.33 to 0.49 for cohort 1 and from 0.17 to 0.22 for cohort 2. Left kidney to background ratio (LKTBR) was significant in all the multiple linear regression combinations (P

Introduction Differences in biochemical parameters of diabetic ketoacidosis in patients with end-stage kidney disease (ESKD) has not been established. Accordingly, we assessed the relationship between degree of metabolic acidosis and ß-hydroxybutyrate in patients with ESKD (eGFR < 15 mL/min/1.73 m2), moderate renal failure (eGFR 15–60), or preserved renal function (eGFR > 60). Methods This observational study included adults (18–80 years) with diabetes ketoacidosis (DKA), admitted to Emory University Hospitals between January 1, 2006 to December 31, 2016. DKA and renal stages were confirmed on admission laboratory values. Results Admission bicarbonate levels (13.9 ± 5 vs 13.4 ± 5.3 vs 13.8 ± 4.2 mmol/L, P = 0.7), and pH levels (7.2 ± 0.3 vs 7.2 ± 0.2 vs 7.2 ± 0.2, P = 0.8) were similar among groups. Patients with ESKD had lower mean ß-hydroxybutyrate level (4.3 ± 3.3 vs 5.6 ± 2.9 vs 5.9 ± 2.5 mmol/L, P = 0.01), but higher admission glucose (852 ± 340.4 vs 714.6 ± 253.3 mg/dL vs 518 ± 185.7 mg/dL, P < 0.01), anion gap (23.4 ± 7.6 vs 23 ± 6.9 vs 19.5 ± 4.7 mmol/L, P < 0.01), and osmolality (306 ± 20.6 vs 303.5 ± vs 293.1 ± 3.1mOsm/kg, P < 0.01) compared with patients with moderate renal failure and preserved renal function, respectively. The sensitivity of ß-hydroxybutyrate > 3 mmol/L for diagnosing DKA by bicarbonate level < 15 and Conclusions Significant metabolic differences were found among DKA patients with different levels of renal function. In patients with ESKD, a ß-hydroxybutyrate level > 3 mmol/L may assist with confirmation of DKA diagnosis.

Plasma cystatin C and shrunken pore syndrome (SPS) are associated with increased mortality in older adults. The objective was to assess the association between these markers of kidney function at admission and mortality in hip fracture patients. Hip fracture patients presenting at Lund University Hospital were eligible for inclusion. Cox regression was used to assess association between plasma cystatin C, creatinine, cystatin C- or creatinine-based estimations of glomerular filtration rate (eGFRCYS and eGFRCREA), or SPS (defined as eGFRCYS/eGFRCREA < 0.7) and mortality during one year follow up. Improvement in discrimination relative to the Nottingham Hip fracture score was assessed by Receiver Operational Characteristics (ROC) analysis and calculation of Net Reclassification Index (NRI). 996 patients were included in the study. Cystatin C, creatinine, eGFRCYS and eGFRCREA were associated with one-year mortality in both unadjusted and adjusted analyses. The association with mortality was stronger for cystatin C and for eGFRCYS than for creatinine and eGFRCREA. Patients with SPS had doubled mortality compared with patients without SPS (43.7 and 20.2%, respectively, p p = .006). None of the markers improved discrimination compared to the Nottingham Hip Fracture Score using ROC analysis whereas eGFRCYS and eGFRCREA improved NRI. Our conclusion is that plasma concentrations of creatinine or cystatin C, eGFRCYS or eGFRCREA or SPS at admission in hip fracture patients are associated with mortality when known risk factors are accounted for. Identification of high risk patients may be improved by eGFRCYS or eGFRCREA.

In Search of a Better Equation Although many experts agree that we should reconsider the use of race in equations for estimated glomerular filtration rate and in medicine more generally, precisely ...

Background: Glomerular filtration rate (GFR) estimation in older adults using a creatinine clearance/24-hour (CrCl) or an equation based on serum creatinine, are often considered equivalent by clinicians. Aim: To compare GFR estimated (eGFR) with the available equations and measured CrCl in patients ≥ 70 years. A secondary aim was to know the differences in chronic kidney disease (CKD) classification, when using the different eGFR formulas. Patients and Methods: In 144 patients aged 77 ± 5 years (58% men), CrCl was measured and GFR was estimated using MDRD, CKD-EPI, BIS-1 and FAS formulas. The eGFR and the stage of CKD were compared according to the different equations used. Results: GFR estimated by MDRD and CKD-EPI equations was 7.8 and 8.4 mL/min/1.73 m2 lower than 24-hour ClCr, respectively. This difference was even greater using the BIS-1 and FAS equations. Twenty-four-hour CrCl classified 47.2% of the patients in a category of renal function > 60 mL/min/1.73 m2, while MDRD and CKD-EPI equations classified just over a third, and BIS-1 and FAS formulas around 20% of the patients. Conclusions: The practice of considering equivalent the GFR estimation using the creatinine-based equations with measured creatinine clearance in older adults should be reconsidered, because their results differ markedly.

Aim Chronic kidney disease (CKD) is associated with unfavorable outcomes in patients with ischemic stroke. One major metabolic derangement of CKD is dyslipidemia, which can be managed by statins. This study aimed to investigate whether the association of statins with post-stroke outcomes would be affected by renal function. Methods We evaluated the association of statin therapy at discharge with 3-month outcomes according to the estimated glomerular filtration rate (eGFR) of 50,092 patients with acute ischemic stroke from the Taiwan Stroke Registry from August 2006 to May 2016. The outcomes were mortality, functional outcome as modified Rankin Scale (mRS), and recurrent ischemic stroke at 3 months after index stroke. Results Statin therapy at discharge was associated with lower risks of mortality (adjusted hazard ratio [aHR], 0.41; 95% confidence interval [CI], 0.34 to 0.50) and unfavorable functional outcomes (mRS 3-5; aHR, 0.80; 95% CI, 0.76 to 0.84) in ischemic stroke patients. After stratification by eGFR, the lower risk of mortality associated with statins was limited to patients with an eGFR above 15 mL/min/1.73 m2. Using statins at discharge was correlated with a lower risk of unfavorable functional outcomes in patients with an eGFR of 60-89 mL/min/1.73 m2. Statin therapy in patients with an eGFR of 60-89 mL/min/1.73 m2 may be associated with a higher risk of recurrent ischemic stroke compared with nonusers (aHR, 1.29; 95% CI, 1.07 to 1.57). Conclusions In patients with acute ischemic stroke, the associations of statins with mortality and functional outcomes was dependent on eGFR.

Background Worsening renal function (WRF) occurs in approximately 25% of acute heart failure patients, and both baseline characteristics and heart failure treatment may increase the risk of WRF. This study aimed to evaluate additional risk factors for WRF in acute heart failure, particularly those related to heart failure treatment. Methods This was a retrospective, observational, analytical study. The inclusion criteria were age 18 years or over, hospital admission due to acute heart failure, and having undergone at least two serum creatinine tests during admission. The eligible patients were classified into two groups: WRF and non-WRF. Predictors for WRF (including treatment parameters) were determined using logistic regression analysis. Results During the study period, there were 301 eligible patients who met the study criteria. Of those, 82 (27.24%) had WRF. There were two independent factors associated with WRF occurrence: baseline diastolic blood pressure and beta blocker treatment, with adjusted odds ratios (95% confidence interval) of 1.060 (1.008, 1.114) and 0.064 (0.006, 0.634), respectively. The Hosmer-Lemeshow Chi square for the final model was 6.11 (p = .634). Conclusions After examining several heart failure treatments and baseline factors, we found that beta blocker treatment results improvement in kidney function.

Background The clinical use of serum creatine (sCr) and cystatin C (CysC) in kidney function evaluation of critically ill patients has been in continuous discussion. The difference between estimated glomerular filtration rate calculated by sCr (eGFRcr) and CysC (eGFRcysc) of critically ill COVID-19 patients were investigated in this study. Methods This is a retrospective, single-center study of critically ill patients with COVID-19 admitted in intensive care unit (ICU) at Wuhan, China. Control cases were moderate COVID-19 patients matched in age and sex at a ratio of 1:1. The eGFRcr and eGFRcysc were compared. The association between eGFR and death were analyzed in critically ill cases. The potential factors influencing the divergence between eGFRcr and eGFRcysc were explored. Results A total of 76 critically ill COVID-19 patients were concluded. The mean age was 64.5 ± 9.3 years. The eGFRcr (85.45 (IQR 60.58–99.23) ml/min/1.73m2) were much higher than eGFRcysc (60.6 (IQR 34.75–79.06) ml/min/1.73m2) at ICU admission. About 50 % of them showed eGFRcysc < 60 ml/min/1.73 m2 while 25% showed eGFRcr < 60 ml/min/1.73 m2 (χ2 = 10.133, p = 0.001). This divergence was not observed in moderate group. The potential factors influencing the divergence included serum interleukin-6 (IL-6), tumor necrosis factor (TNF-α) level as well as APACHEII, SOFA scores. Reduced eGFRcr (

BACKGROUND: Rapid kidney decline is associated with mortality and cardiovascular disease, even in the absence of chronic kidney disease. American Indians (AI) have particularly high burden of kidney disease, cardiovascular disease, and stroke. This study aims to examine extreme loss in glomerular function in this population in association with clinical outcomes. METHODS: The Strong Heart Study, a large longitudinal cohort of adult AI participants, collected plasma creatinine at 3 examination visits between 1989–1999. Intraindividual regressions of estimated glomerular filtration rate (eGFR) provided linear estimates of change in kidney function over this time period. Surveillance with physician adjudication identified mortality and cardiovascular events between visit 3 through 2017. RESULTS: Mean change in eGFR was loss 6.8 mL/min over the ten year baseline (range: −66.0 to +28.9 mL/min). The top 1 percentile lost approximately 5.7 mL/min/year. Participants with extreme eGFR loss were more likely to have diabetes (95% vs 71%), hypertension (49% vs 33%), or longer smoking history, among smokers (19 pack years vs 17 pack years). CKD (eGFR20 mL/min over baseline period) was associated with mortality, independent of baseline eGFR: HR 3.5 (95% CI 2.7–4.4), and also independently associated with composite CVD events and CHF: HR 1.4 and 1.7 (95% CI 1.1–1.9 and 1.2–2.6), respectively. CONCLUSION: This is the first examination of decline in eGFR in association with mortality and CVD among AIs. The implications of these findings are broad: clinical evaluation may benefit from evaluating change in eGFR over time in addition to dichotomous eGFR. Also, these findings suggest there may be aspects of renal function that are not well-marked by clinical CKD, but which may have particular relevance to long-term renal and vascular health.

BackgroundCharacterizing the dynamics of serum creatinine concentrations (Scr) and associated creatinine clearance (CLcr) as a measure of kidney function in extremely low birth weight (≤ 1000 g; ELBW) neonates remains challenging.MethodsWe performed a retrospective study that included longitudinal Scr (enzymatic assay) data from 148 ELBW neonates up to 6 weeks after birth. Change of Scr and inter-individual variability was characterized with nonlinear mixed-effect modeling. Key covariates such as gestational age (GA), mode of delivery (MOD), and treatment with ibuprofen or inotropic agents were investigated.ResultsA total of 2814 Scr concentrations were analyzed. GA was associated with Scr at birth (higher with advancing GA), and GA and MOD showed an association with postnatal maturation of CLcr (faster clearance increase with advancing GA and after C-section). Small CLcr decrease (≤ 5%) was quantified during ibuprofen treatment. For a GA of 27 weeks, mean Scr (estimated CLcr) at birth was 0.61 mg/dl (0.23 ml/min), increasing to 0.87 mg/dl (0.27 ml/min) at day three, and decreasing to 0.36 mg/dl (0.67 ml/min) at day 42 after birth.ConclusionsWe report the first mathematical model able to characterize Scr and CLcr in ELBW neonates during the first 6 weeks of life in a quantitative manner as a function of GA, MOD, and ibuprofen treatment. This model allows the derivation of GA-adjusted reference ranges for ELBW neonates and provides a rationale for normative Scr concentrations, and as such will help clinicians to further optimize monitoring and treatment decisions in this vulnerable patient population.

Glomerular filtration rate (GFR) is routinely estimated using endogenous biomarkers due to the complexity of direct measurement methods. Cystatin C is a protease inhibitor produced in all nucleated cells. It is freely filtered and then catabolized by renal tubular cells. Therefore, plasma concentration of cystatin C depends primarily on GFR. Serum cystatin C is less affected by muscle mass, diet, race, gender and age than creatinine. In the general population, equations to estimate GFR based on cystatin C do not have a better performance than those based on creatinine. However, formulas that combine creatinine and cystatin C are more accurate and precise. Estimation of GFR based on cystatin C could be useful in populations in which creatinine value may be biased, such as people with extremely low or high muscle mass, cirrhosis and chronic cardiorenal syndrome. Due to its higher cost in comparison to creatinine, we recommend measuring cystatin C on these clinical situations and when a more accurate estimation of GFR is required.

The association between alcohol consumption and kidney function is intriguing, but study results are mixed and controversial. We examined the association of alcohol consumption with the overall change in kidney function over 12 years. We analyzed data from a population-based cohort that was part of the Korean Genome and Epidemiology Study. Primary exposure was total alcohol intake (non-drinkers, 0 to

Introduction: Large randomized trials testing the effect of a multifactorial weight-loss lifestyle intervention including Mediterranean diet (MedDiet) on renal function are lacking. Here, we evaluated the 1-year efficacy of an intensive weight-loss intervention with an energy-reduced MedDiet (erMedDiet) plus increased physical activity (PA) on renal function. Methods: Randomized controlled "PREvención con DIeta MEDiterránea-Plus"(PREDIMED-Plus) trial is conducted in 23 Spanish centers comprising 208 primary care clinics. Overweight/obese (n = 6,719) adults aged 55-75 years with metabolic syndrome were randomly assigned (1:1) to an intensive weight-loss lifestyle intervention with an erMedDiet, PA promotion, and behavioral support (intervention) or usual-care advice to adhere to an energy-unrestricted MedDiet (control) between September 2013 and December 2016. The primary outcome was 1-year change in estimated glomerular filtration rate (EGFR). Secondary outcomes were changes in urine albumin-to-creatinine ratio (UACR), incidence of moderately/severely impaired EGFR (, This work was supported by the official Spanish Institutions for funding scientific biomedical research, CIBER Fisiopatología de la Obesidad y Nutrición (CIBEROBN) and Instituto de Salud Carlos III (ISCIII), through the Fondo de Investigación para la Salud (FIS), which is cofunded by the European Regional Development Fund (5 coordinated FIS projects leaded by J.S.-S and J.V., including the following projects: PI13/00673, PI13/00492, PI13/00272, PI13/01123, PI13/00462, PI13/00233, PI13/02184, PI13/00728, PI13/01090, PI13/01056, PI14/01722, PI14/00636, PI14/00618, PI14/00696, PI14/01206, PI14/01919, PI14/00853, PI14/01374, PI14/00972, PI14/00728, PI14/01471, PI16/00473, PI16/00662, PI16/01873, PI16/01094, PI16/00501, PI16/00533, PI16/00381, PI16/00366, PI16/01522, PI16/01120, PI17/00764, PI17/01183, PI17/00855, PI17/01347, PI17/00525, PI17/01827, PI17/00532, PI17/00215, PI17/01441, PI17/00508, PI17/01732, PI17/00926; PI19/00957, PI19/00386, PI19/00309, PI19/01032, PI19/00576, PI19/00017, PI19/01226, PI19/00781, PI19/01560, and PI19/01332); the Especial Action Project entitled Implementación y evaluación de una intervención intensiva sobre la actividad física Cohorte PREDIMED-Plus grant to J.S.-S.; the European Research Council (Advanced Research Grant 2014–2019; agreement #340918) granted to M.Á.M.-G.; the Recercaixa (No. 2013ACUP00194) grant to J.S.-S.; grants from the Consejería de Salud de la Junta de Andalucía (PI0458/2013, PS0358/2016, and PI0137/2018); the PROMETEO/2017/017 grant from the Generalitat Valenciana; the SEMERGEN grant; funds from the European Regional Development Fund (CB06/03); International Nut & Dried Fruit Council – FESNAD (Long-term effects of an energyrestricted Mediterranean diet on mortality and cardiovascular disease 2014–2015, No. 201302) (PI: M.Á.M.-G.); the AstraZeneca Young Investigators Award in Category of Obesity and T2D 2017 (PI: D.R.); grant of support to research groups No. 35/2011 (Balearic Islands Gov.; FEDER funds) (J.A.T. and C.B.); the JR17/00022 (ISCIII) grant to O.C.; the Boosting young talent call grant program for the development of IISPV research projects 2019–2021 (Ref.: 2019/IISPV/03 grant to A.D.-L.); the Societat Catalana d’Endocrinologia i Nutrició (SCEN) Clinical-Research Grant 2019 (IPs: J.S.-S. and A.D.-L.). Collaborative Nutrition and/or Obesity Project for Young Researchers 2019 supported by CIBEROBN entitled Lifestyle Interventions and Chronic Kidney Disease: Inflammation, Oxidative Stress and Metabolomic Profile (LIKIDI study) grant to A.D.-L.

Background The study aimed to construct a clinical model based on preoperative data for predicting acute kidney injury (AKI) following cardiac surgery in patients with normal renal function. Methods A total of 22,348 consecutive patients with normal renal function undergoing cardiac surgery were enrolled. Among them, 15,701 were randomly selected for the training group and the remaining for the validation group. To develop a model visualized as a nomogram for predicting AKI, logistic regression was performed with variables selected using least absolute shrinkage and selection operator regression. The discrimination, calibration, and clinical value of the model were evaluated. Results The incidence of AKI was 25.2% in the training group. The new model consisted of nine preoperative variables, including age, male gender, left ventricular ejection fraction, hypertension, hemoglobin, uric acid, hypomagnesemia, and oral renin-angiotensin system inhibitor and non-steroidal anti-inflammatory drug within 1 week before surgery. The model had a good performance in the validation group. The discrimination was good with an area under the receiver operating characteristic curve of 0.740 (95% confidence interval, 0.726–0.753). The calibration plot indicated excellent agreement between the model prediction and actual observations. Decision curve analysis also showed that the model was clinically useful. Conclusions The new model was constructed based on nine easily available preoperative clinical data characteristics for predicting AKI following cardiac surgery in patients with normal kidney function, which may help treatment decision-making, and rational utilization of medical resources.

The effects of glucagon-like peptide-1 receptor agonists (GLP-1RAs) on renal outcomes in patients with type 2 diabetes at high cardiovascular risk are modest or neutral. However, GLP-1RAs may confer clinical benefits in those at high risk of progressive renal function loss. We examined the effects of once-weekly exenatide (EQW) on estimated glomerular filtration rate (eGFR) slope and urinary albumin:creatinine ratio (UACR) as a function of baseline UACR in 3503 EXSCEL participants (23.7%) with eGFR data available and 2828 participants (19.2%) with UACR change data available. EQW improved eGFR slope assessed via mixed model repeated measures, compared with placebo, in participants with baseline UACR >100 mg/g (0.79 mL/min/1.73 m2/year [95% confidence interval {CI} 0.24–1.34]) and UACR >200 mg/g (1.32 mL/min/1.73 m2/year [95% CI 0.57–2.06]), but not at lower UACR thresholds. EQW reduced UACR, compared with placebo, assessed via analysis of covariance, consistently across subgroups with baseline UACR >30 mg/g (28.2% reduction), baseline UACR >100 mg (22.5% reduction) and baseline UACR >200 mg (34.5% reduction). This post hoc EXSCEL analysis suggests that EQW reduces UACR, with improvement in eGFR slope specifically in participants with elevated baseline UACR.

Background. Iodinated contrast (IC) is a leading cause of hospital-based acute kidney injury (AKI). Contrast-induced acute kidney injury (CI-AKI) is a decline in renal function due to iodinated contrast administration and occurs more frequently in individuals with increasingly common risk factors, such as diabetes mellitus (DM). Physical training (PT) can have renoprotective effects on CI-AKI in diabetic nephropathy. The aim of this study was to evaluate the injury in kidneys of diabetic rats submitted to treatment with IC, evaluating the impact of PT on hemodynamics and renal function in addition to oxidative profile in diabetic rats submitted to IC-AKI. Materials and Methods. Adult male Wistar rats are randomized into four groups: citrate ( n = 7 ): control group, citrate buffer (streptozotocin-STZ vehicle), intravenous tail (iv), single dose; DM ( n = 7 ): STZ, 60 mg/kg, iv, single dose; DM+IC ( n = 7 ): DM rats treated with IC (sodium meglumine ioxithalamate, 6 mL/kg, intraperitoneal (ip), single dose); DM+IC+PT ( n = 7 ): DM rats treated with IC as mentioned and submitted to physical training. Renal function parameters (inulin clearance, neutrophil gelatinase-associated lipocalin (NGAL), serum creatinine, and urinary albumin), hemodynamics (renal blood flow and renal vascular resistance), and oxidative profile (urinary peroxides, urinary TBARS, urinary nitric oxide, and renal tissue thiols) were evaluated. Results. It was possible to observe a decrease in inulin clearance, renal blood flow, and thiols in renal tissue accompanied by an increase in urinary flow, serum creatinine, urinary albumin, renal vascular resistance, urinary peroxides, urinary nitrate, and TBARS in the DM group compared to the citrate group. The DM+IC group showed a reduction in inulin clearance, and the renal dysfunction was also seen by the increased NGAL. Renal hemodynamics and oxidative profile compared were also worsened in the DM group. PT improved renal function by increasing renal blood flow and thiol levels in renal tissue and reduced renal vascular resistance, metabolites of reactive oxygen, nitrogen species, and lipid peroxidation in the DM+IC+PT group compared to DM+IC. Conclusions. Our results confirmed that DM induction increases renal vulnerability to the toxicity of IC and an association between DM with IC predisposes to severe AKI with reduced renal function alongside with renal hemodynamic alterations and oxidative mechanism of injury. The PT showed a renoprotective effect in DM animals subjected to damage with IC by modulating renal hemodynamics and oxidative profile, confirming a potential to modify the risk of CI-AKI when diabetes mellitus is present.

Coronavirus disease 2019 (COVID-19) poses an unprecedented challenge to world health systems, substantially increasing hospitalization and mortality rates in all affected countries. Being primarily a respiratory disease, COVID-19 is mainly associated with pneumonia or minor upper respiratory tract symptoms; however, different organs can sustain considerable (if not terminal) damage because of coronavirus. Acute kidney injury is the most common complication of COVID-19-related pneumonia, and more than 20% of patients requiring ventilatory support develop renal failure. Additionally, chronic kidney disease is a major risk factor for COVID-19 severity and mortality. All these data demonstrate the relevance of renal function assessment in patients with COVID-19 and the need of early kidney-directed diagnostic and therapeutic approaches. However, the sole assessment of renal function could be not entirely indicative of kidney tissue status. In this viewpoint, we discuss the clinical significance and potential relevance of renal functional reserve evaluation in patients with COVID-19.

Bezafibrate (BzF) is eliminated by renal excretion and dosage must be reduced in patients with chronic kidney disease (CKD). There is a concern that BzF causes a further deterioration in renal function in patients with CKD. This study assessed whether BzF discontinuation or dose reduction in CKD patients improves renal function. 117 CKD patients treated with BzF between 2009 and 2014 were studied for demographics, comorbid conditions and laboratory variables. Data compared 2 groups: an intervention group of 64 patients where recommendations regarding BzF administration was implemented and a control group of 37 patients. Follow-up was maintained for 12 months. In the intervention group, estimated glomerular filtration rate (eGFR) increased from 38 to 42 mL/min/1.73 m2 (p = 0.01); blood urea levels decreased from 81 to 77 mg/dL (p = 0.04). Serum creatinine decreased by more than 0.2 mg/dL in 45% of the intervention group, as compared to 19% of the control group (p 2). In the intervention group, TG level increased from 183 to 220 mg/dL (p

IgG4-related disease (IgG4-RD) is an immune-mediated disorder often showing elevated serum IgG4 concentrations, dense T and B lymphocyte infiltration, and IgG4-positive plasma cells and storiform fibrosis. We prospectively evaluated for 4 years 5 patients with histologically proven IgG4-RD of whom 3 had tubulointerstitial nephritis (TIN) and 2 had retroperitoneal fibrosis (RPF). They received an intensive B depletion therapy with rituximab. The estimated glomerular filtration rate of TIN patients after 1 year increased from 9 to 24 ml/min per 1.73 m2. IgG/IgG4 dropped from 3236/665 to 706/51 mg/dl, C3/C4 went up from 49/6 to 99/27 mg/dl, and the IgG4-RD responder index fell from 10 to 1. CD20+ B cells decreased from 8.7 to 0.5%. A striking drop in interstitial plasma cell infiltrate as well as normalization of IgG4/IgG-positive plasma cells was observed at repeat biopsy. Both clinical and immunological improvement persisted over a 4-year follow-up. Treating these patients who were affected by aggressive IgG4-RD with renal involvement in an effort to induce a prolonged B cells depletion with IgG4 and cytokine production decrease resulted in a considerable rise in eGFR, with IgG4-RD RI normalization and a noteworthy improvement in clinical and histological features. Furthermore, the TIN subgroup was shown not to need for any maintenance therapy.

The importance of kidney damage in obese patients is due to the increasing incidence of nephropathies associated with metabolic disorders, their predisposition to a progressive course of the disease, and the need to optimize early disease detection. The purpose of our work is to study the level of cystatin C, ghrelin, and their interrelation in patients with early stages (I-II) of chronic kidney disease (CKD) against the background of obesity. The indicators of daily microalbuminuria in patients of both groups were studied, and it was found that in patients with stage 2 CKD with obesity, it was 1.2 times higher than in patients with stage 1 CKD with obesity. Patients of the second group revealed a direct middle correlation between daily albuminuria and body mass index (BMI), which indicates deterioration in the functional state of the kidneys against the background of obesity. We obtained an increase in the serum concentration of cystatin C in stage 2 CKD with obesity, reflecting the state of glomerular filtration and the degree of renal function decrease. Correlation analysis showed a positive relation of cystatin C with increased urinary albumin excretion in both groups, plasma creatinine content, BMI, and age. Simultaneously with the increase in the level of cystatin C and the decrease in the glomerular filtration rate, there was an increase in ghrelin levels in stage 2 CKD and the progression of obesity, while such dependence was not seen in stage 1 CKD.

Objectives To compare the effects of restoring mean arterial pressure with vasopressin or norepinephrine on systemic hemodynamics, renal blood flow, intrarenal perfusion and oxygenation, and renal function in ovine septic acute kidney injury. Design Interventional Study. Setting Research Institute. Subjects Adult Merino ewes. Interventions Flow probes were implanted on the pulmonary and renal arteries (and the mesenteric artery in sheep that received vasopressin). Fiber-optic probes were implanted in the renal cortex and medulla to measure tissue perfusion and oxygen tension (PO2). Conscious sheep were administered Escherichia coli to induce septic acute kidney injury. Vasopressin (0.03 IU/min [0.03-0.05 IU/min]; n = 7) or norepinephrine (0.60 μg/kg/min [0.30-0.70 μg/kg/min]; n = 7) was infused IV and titrated to restore baseline mean arterial pressure during 24-30 hours of sepsis. Measurements and main results Ovine septic acute kidney injury was characterized by reduced mean arterial pressure (-16% ± 2%) and creatinine clearance (-65% ± 9%) and increased renal blood flow (+34% ± 7%) but reduced renal medullary perfusion (-44% ± 7%) and PO2 (-47% ± 10%). Vasopressin infusion did not significantly affect renal medullary perfusion or PO2 and induced a sustained (6 hr) ~2.5-fold increase in creatinine clearance. Vasopressin reduced sepsis-induced mesenteric hyperemia (+61 ± 13 to +9% ± 6%). Norepinephrine transiently (2 hr) improved creatinine clearance (by ~3.5-fold) but worsened renal medullary ischemia (to -64% ± 7%) and hypoxia (to -71% ± 6%). Conclusions In ovine septic acute kidney injury, restoration of mean arterial pressure with vasopressin induced a more sustained improvement in renal function than norepinephrine, without exacerbating renal medullary ischemia and hypoxia or reducing mesenteric blood flow below baseline values.

Background Patients with primary hyperparathyroidism (pHPT) and impaired kidney function (estimated glomerular filtration rate (eGFR) Methods Historic cohort study. From the Danish National Patient Registry (NPR) and major medical biochemistry laboratories in Denmark, we identified 3585 patients with biochemically confirmed pHPT among whom n = 1977 (55%) were treated with PTX (PTX-group) whereas n = 1608 (45%) were followed without surgery (non-PTX group). Baseline was defined as time of diagnosis and kidney function was re-assessed 9–15 months after PTX (PTX group) or 9–15 months after diagnosis (non-PTX group). Results At follow-up, eGFR had decreased significantly in the PTX- compared to the non-PTX-group (median − 4% vs. − 1%, p 90 mL/min, but not for those with lower eGFR values. Findings did not differ between patients with mild compared to moderate/severe hypercalcemia. However, after mutual adjustments, we identified baseline levels of calcium, PTH, and eGFR as well as age and treatment (PTX vs. no-PTX) as independent predictors for changes in kidney function. Conclusion Compared to non-surgical surveillance, PTX is associated with a small but significant decrease in kidney function in pHPT patients with an initial normal kidney function.

Introduction: Cold ischemia-reperfusion injury (IRI) is an inevitable event that increases post-transplant complications. We have previously demonstrated that supplementation of University of Wisconsin (UW) solution with non-FDA-approved hydrogen sulfide (H2S) donor molecules minimizes cold IRI and improves renal graft function after transplantation. The present study investigates whether an FDA-approved H2S donor molecule, sodium thiosulfate (STS), will have the same or superior effect in a clinically relevant rat model of syngeneic orthotopic kidney transplantation. Method: Thirty Lewis rats underwent bilateral nephrectomy followed by syngeneic orthotopic transplantation of the left kidney after 24-hour preservation in either UW or UW+STS solution at 4 °C. Rats were monitored to post-transplant day 14 and sacrificed to assess renal function (urine output, serum creatinine and blood urea nitrogen). Kidney sections were stained with H&E, TUNEL, CD68, and myeloperoxidase (MPO) to detect acute tubular necrosis (ATN), apoptosis, macrophage infiltration, and neutrophil infiltration. Result: UW+STS grafts showed significantly improved graft function immediately after transplantation, with improved recipient survival compared to UW grafts (p

In addition to their fundamental role in clearance, the kidneys release select molecules into the circulation, but whether any of these anabolic functions provides insight on kidney health is unknown. Using aptamer-based proteomics, we characterized arterial (A)-to-renal venous (V) gradients for >1,300 proteins in 22 individuals who underwent invasive sampling. Although most of the proteins that changed significantly decreased from A to V, consistent with renal clearance, several were found to increase, the most significant of which was testican-2. To assess the clinical implications of these physiologic findings, we examined proteomic data in the Jackson Heart Study (JHS), an African-American cohort (n = 1,928), with replication in the Framingham Heart Study (FHS), a White cohort (n = 1,621). In both populations, testican-2 had a strong, positive correlation with estimated glomerular filtration rate (eGFR). In addition, higher baseline testican-2 levels were associated with a lower rate of eGFR decline in models adjusted for age, gender, hypertension, type 2 diabetes, body mass index, baseline eGFR, and albuminuria. Glomerular expression of testican-2 in human kidneys was demonstrated by immunohistochemistry, immunofluorescence, and electron microscopy, while single-cell RNA sequencing of human kidneys showed expression of the cognate gene, SPOCK2, exclusively in podocytes. In vitro, testican-2 increased glomerular endothelial tube formation and motility, raising the possibility that its secretion has a functional role within the glomerulus. Taken together, our findings identify testican-2 as a podocyte-derived biomarker of kidney health and prognosis.