Early Kidney Dysfunction Research Articles

Development of a kidney microphysiological system hardware platform for microgravity studies

Determining the physiological effects of microgravity on the human kidney is limited to relatively insensitive tests of biofluids (blood and urine) that do not return abnormal results until more than 50% of kidney function is lost. We have developed an “organ on chip” microphysiological model of the human kidney proximal tubule (PT-MPS) that can recapitulate many kidney functions and disease states and could play a critical role in determining mechanisms of early kidney dysfunction in microgravity. However, the ground-based PT-MPS system is incompatible with spaceflight as it requires a large pneumatic system coupled to a cell incubator for perfusion and intensive hand-on manipulation. Herein, we report the hardware engineering and performance of the Kidney Chip Perfusion Platform (KCPP), a small, advanced, semi-autonomous hardware platform to support kidney microphysiological model experiments in microgravity. The KCPP is composed of five components, the kidney MPS, the MPS housing and valve block, media cassettes, fixative cassettes, and the programable precision syringe pump. The system has been deployed twice to the ISSNL (aboard CRS-17 and CRS-22). From each set of ISSNL experiments and ground-based controls, we were able to recover PT-MPS effluent for biomarker analysis and RNA suitable for transcriptomics analysis demonstrating the usability and functionality of the KCPP.

Glycoprotein Acetyls Associate With Intraglomerular Hemodynamic Dysfunction, Albuminuria, Central Adiposity, and Insulin Resistance in Youth With Type 1 Diabetes

ObjectivesGlycoprotein acetyls (GlycA's) are biomarkers of systemic inflammation and cardiovascular disease, yet little is known about their role in type 1 diabetes (T1D). In this study we examined the associations among GlycA's, central adiposity, insulin resistance, and early kidney injury in youth with T1D. MethodsGlomerular filtration rate and renal plasma flow by iohexol and p-aminohippurate clearance, urine albumin-to-creatinine ratio (UACR), central adiposity by dual-energy x-ray absorptiometry, and estimated insulin sensitivity were assessed in 50 youth with T1D (16±3.0 years of age, 50% female, glycated hemoglobin 8.7%±1.3%, T1D duration 5.7±2.6 years). Concentrations of GlycA were quantified by targeted nuclear magnetic resonance spectroscopy. Correlation and multivariable linear regression analyses were performed. ResultsGlycA's were higher in girls vs boys (1.05±0.26 vs 0.84±0.15 mmol/L, p=0.001) and in participants living with overweight/obesity vs normal weight (1.12±0.23 vs 0.87±0.20 mmol/L, p=0.0004). GlycA's correlated positively with estimated intraglomerular pressure (r=0.52, p=0.001), UACR (r=0.53, p<0.0001), and trunk mass (r=0.45, p=0.001), and inversely with estimated insulin sensitivity (r=−0.36, p=0.01). All relationships remained significant after adjustment for age, sex, and glycated hemoglobin. ConclusionsAs biomarkers of inflammation, GlycA's were higher in girls and those with overweight or obese body habitus in T1D. GlycA's associated with parameters of early kidney dysfunction, central adiposity, and insulin resistance.

Renal Transplant in Elderly End-Stage Renal Disease Patients: Impact of Comorbidities and Posttransplant Adverse Events on Outcomes.

Elderly renal transplant continues to be debated because of age-related factors affecting transplant success and long-term prognosis. We investigated the effects ofrecipient age and predictors of renal transplant outcomes in elderly renal transplant recipients. We retrospectively analyzed 506 patients who had a first renal transplant between January 2010 and December 2020; there were 165 recipients aged ≥60 years (elderly) and 341 recipients aged <60 years (young).We collected recipient, donor, and transplant characteristics and assessed 1-, 3-, and 5-year overall patient and death-censored graft survival and risk factors influencing outcomes ofrenal transplant in elderly recipients. Elderly recipients showed significantly lower 1-, 3-, and 5-year patient survival rates (96.3%, 89.8%, 80.9%) than young recipients (98.8%, 98.5%, 97.8%; P < .001). However, death-censored graft survival rates were not significantly different (P = .459) between elderly (96.3%, 94.3%, 93.2%) and young recipients (97.7%, 97.0%, 93.9%). Advanced recipient age was identified as an independent risk factor for patient survival, irrespective of donor age. In elderly recipients, male gender (hazard ratio 2.013; 95% CI, 1.110-3.649), pretransplant cardiovascular disease (hazard ratio 1.774; 95% CI, 1.030-3.553), and posttransplant chestinfection (hazard ratio 2.421; 95% CI, 1.439-4.076) were significant predictors of inferior patient survival. Proteinuria at 1 month (hazard ratio 1.006; 95% CI, 1.000-1.011) and low estimated glomerular filtration rate at 3 months (hazard ratio 0.943; 95% CI, 0.899-0.988) posttransplant were early predictors of worse death-censored graft survival. Elderly renaltransplantrecipients showed promising 5-year patient and death-censored graft survival, exceeding 80%, despite higher mortality risk compared with young recipients. Optimizing outcomes of elderly renal transplant necessitates a multifaceted approach encompassing meticulous pretransplant cardiovascular disease assessment, rigorous posttransplant chest infection prevention and management, and proactive monitoring for early posttransplant kidney dysfunction, to permit timely intervention.

Early Kidney and liver Dysfunction Associated with Exposure to Crude Oil in Al-Ahdab field

Although the detrimental effects of crude oil on many types of plants and animals have been broadly studied, not enough research has been done on how exposure to oil affects human health. In the present work, we tried to inspect their effect on the liver and kidney functions of the Al-Ahdab field workers as well as the local population living close to the oil drilling sites (Fadak city). A randomly selected 150 subjects they don’t suffer from chronic diseases (50 subjects from workeres of Al-Ahdab field They have been working in the field for more than ten years and 50 subjects from Fadak city they don’t work in the Al-Ahdab field and 50 subjects from Al- kut city far from the Al-Ahdab field also they don’t work in the Al-Ahdab field as control) aged higher than 40 years were taken under consideration. The level of urea, creatinine, bilirubin, aspartate transaminase and alanine transaminase enzymes in serum were evaluated by spectrophotometer. Where it was found that the levels of urea, creatinine, liver enzymes, and bilirubin were higher among the Al-Ahdab field workers than the control. We also found that the residents of Fadak City, which is very close to the Al-Ahdab field oil extraction, were also high compared to the control but less than the Al-Ahdab field workers. The study reveals that long-term exposure to the pollutants produce from oil extraction may lead to harm effect to liver and kidney functions of workers in oil extraction field and populations living in polluted sites.

Urinary Albumin-to-Creatinine Ratio in Normal Range, Cardiovascular Health, and All-Cause Mortality

Although cumulative evidence suggests that elevated urinary albumin-to-creatinine ratio (UACR) in the normal range (<30 mg/g) may be associated with an increased risk of mortality, few studies have investigated whether cardiovascular health (CVH) modifies the harmful outcomes of high-normal UACR. To investigate associations of traditionally normal UACR and CVH with all-cause mortality. This cohort study used National Health and Nutrition Examination Survey data from 2005 through 2018 and linked mortality information until 2019. Data were analyzed from March 1 through October 31, 2023. The study included adult participants aged 20 to 79 years with a normal UACR (<30 mg/g) based on Kidney Disease: Improving Global Outcomes criteria. The UACR was treated as a continuous variable and categorized into tertiles delineated as low (<4.67 mg/g), medium (4.67-7.67 mg/g), and high (7.68 to <30 mg/g). Cardiovascular health was assessed using Life's Essential 8 scores and grouped as poor (0-49 points), moderate (50-79 points), and ideal (80-100 points). Multivariable Cox proportional hazards regression was used to estimate hazard ratios (HRs) and 95% CIs for associations of UACR with all-cause mortality in total participants and as stratified by CVH groups. The study included 23 697 participants (mean [SD] age, 45.58 [15.44] years; 11 806 women [49.7%] and 11 891 men [50.3%]). During the median 7.8 years (range, 4.5-11.1 years) of follow-up, 1403 deaths were recorded. Near-linear associations were observed for continuous UACR and CVH with all-cause mortality. Compared with the low UACR group, high UACR in the normal range showed an increased mortality risk in the moderate and poor CVH groups (CVH [50-79]: HR, 1.54 [95% CI, 1.26-1.89]; CVH [0-49]: HR, 1.56 [95% CI, 1.10-2.20]), with a significant multiplicative interaction of UACR and CVH (P < .001). The findings suggest that high UACR within the normal range is associated with a significantly increased risk of all-cause mortality, with the association more pronounced in adults with poor CVH status. These findings highlight the importance of risk management for early kidney dysfunction, particularly among individuals with poor CVH.

1148-P: Glycoprotein Acetyls (GlycA) Associate with Intraglomerular Hemodynamic Dysfunction, Albuminuria, Central Adiposity, and Insulin Resistance (IR) in Youth with Type 1 Diabetes (T1D)

GlycA is a biomarker of systemic inflammation and cardiovascular disease, yet little is known about this biomarker in T1D. We examined the associations among GlycA, central adiposity, IR, and early kidney injury in adolescents with T1D. Glomerular filtration rate (GFR) and renal plasma flow (RPF) by iohexol and p-aminohippurate clearance, respectively, urine albumin-to-creatinine ratio (UACR), central adiposity by dual-energy x-ray absorptiometry (DXA), and estimated insulin sensitivity (eIS) by the CACTI equation were assessed in youth with T1D (n=50, 16.0±3.0 years, 50% female, HbA1c 8.7±1.3%, T1D duration 5.7±2.6 years, UACR 6 [5-14] mg/g, GFR 189±40 mL/min). Intraglomerular pressure (PGLO) was estimated by the Gomez equations. Concentrations of GlycA were quantified by targeted nuclear magnetic resonance spectroscopy. Correlation and multivariable linear regression analyses were performed. GlycA was higher in girls vs. boys (1.05±0.26 vs. 0.84±0.15 mmol/L, p=0.001), and in participants who were overweight or obese vs. normal weight (1.12±0.23 vs. 0.87±0.20, p=0.0004). GlycA correlated positively with estimated PGLO (r=0.52, p=0.001), UACR (r=0.53, p&amp;lt;0.0001) and trunk mass (r=0.45, p=0.001) and negatively with eIS (r=-0.36, p=0.01). All relationships remained significant after adjustment for age, sex, and HbA1c. In youth with T1D, GlycA, a biomarker of inflammation, was found to be higher in girls with T1D and those of overweight/obese habitus, compared to boys with T1D. Additionally, GlycA associated with parameters of early kidney dysfunction, central adiposity, and IR. Disclosure T.Reinicke: None. S.Gross: None. D.Cherney: Other Relationship; Boehringer Ingelheim-Lilly, Merck, AstraZeneca, Sanofi, Mitsubishi-Tanabe, Abbvie, Janssen, Bayer, Prometic, BMS, Maze, Gilead, CSL-Behring, Otsuka, Novartis, Youngene, Lexicon and Novo-Nordisk, Research Support; Boehringer Ingelheim-Lilly, Merck, Janssen, Sanofi, AstraZeneca, CSL-Behring and Novo-Nordisk. T.B.Vigers: None. L.Pyle: None. L.Driscoll: None. F.H.Mahmud: None. A.Dart: None. M.E.Pavkov: None. R.G.Nelson: None. P.Bjornstad: Advisory Panel; AstraZeneca, Novo Nordisk, Lilly, Horizon Therapeutics plc, Boehringer Ingelheim (Canada) Ltd., LG Chem, Consultant; Bayer Inc., Bristol-Myers Squibb Company. A.Caldwell-mcgee: None. C.Birznieks: None. D.Carrasco: None. M.Marcovecchio: None. K.J.Nadeau: None. K.L.Tommerdahl: None. M.Pauley: None. J.K.Snell-bergeon: None. Funding Junior Research Fellowship Award

COMPARISON BETWEEN CENTRAL AND AUTOMATED PERIPHERAL BLOOD PRESSURE MEASUREMENT FOR EARLY DETECTION OF KIDNEY DYSFUNCTION IN HYPERTENSIVE PATIENTS

Objective: To assess the difference of blood pressure measurements using central and automated peripheral blood pressure measurement (oscillometric) devices among patients with primary hypertension for early detection of kidney dysfunction and the validity of automated BP measurement device compared with non-invasive central BP measurement device for diagnosis of hypertension. Also, to link between parameters such as augmentation index and pulse wave velocity index and early kidney dysfunction markers. Design and method: The study is a case-comparative study that included 201 patients with primary hypertension (108 patients with chronic kidney disease and 93 patients without kidney disease). Exclusion criteria were patients presenting with secondary hypertension, diabetes mellitus (DM), end stage renal disease (ESRD) on regular dialysis, young patients below 40 and above 70 years old and patients with collagen diseases. All patients underwent blood pressure measurement by OMRON M2 and Mobil-O-Graph devices, kidney function assessment and abdominal ultrasonography. Results: Patients with chronic kidney disease were significantly older (60.02±9.1 vs. 55.33±8.5; P &lt; 0.001), with longer duration of hypertension (7.56±5.9 vs. 6.05±5.8; P = 0.020) in comparison to those without chronic kidney disease. Automated peripheral measurement of systolic blood pressure, diastolic blood pressure and pulse pressure were significantly higher in comparison to central blood pressure. Patients with chronic kidney disease had significantly higher augmentation index (24.06±12.6 vs. 19.02±10.8; P &lt; 0.001) and pulsed wave velocity (8.66±1.5 vs. 8.69±6.8; P = 0.004) in comparison to those without chronic kidney disease. Augmentation index had positive correlation with pulse wave velocity (r = 0.183, P = 0.005). There was negative correlation between both pulse wave velocity and augmentation index and estimated glomerular filtration rate (r = -0.318, P &lt; 0.001), and (r = -0.236, P &lt; 0.001), respectively. Hence, arterial stiffness parameters are good positive test for prediction of chronic kidney disease. Conclusions: There is a strong agreement between non-invasive centrally and automated peripherally measured blood pressure in diagnosis of hypertension. But non-invasive central measurements are preferred over automated measurements for early prediction and detection of renal impairment.

Metabolically healthy obesity is associated with higher risk of both hyperfiltration and mildly reduced estimated glomerular filtration rate: the role of serum uric acid in a cross-sectional study

BackgroundThe impact of metabolically healthy obesity (MHO) on kidney dysfunction remains debatable. Moreover, few studies have focused on the early stages of kidney dysfunction indicated by hyperfiltration and mildly reduced eGFR. Thus, we aimed to investigate the association between the MHO and early kidney dysfunction, which is represented by hyperfiltration and mildly reduced estimated glomerular filtration rate (eGFR), and to further explore whether serum uric acid affects this association.MethodsThis cross-sectional study enrolled 1188 residents aged ≥ 40 years old from Yonghong Communities. Metabolically healthy phenotypes were categorized based on Adult Treatment Panel III criteria. Obesity was defined as body mass index (BMI) ≥ 25 kg/m2. Mildly reduced eGFR was defined as being in the range 60 < eGFR ≤ 90 ml/min/1.73m2. Hyperfiltration was defined as eGFR > 95th percentile after adjusting for sex, age, weight, and height.ResultsOverall, MHO accounted for 12.8% of total participants and 24.6% of obese participants. Compared to metabolically healthy non-obesity (MHNO), MHO was significantly associated with an increased risk of mildly reduced eGFR (odds ratio [OR] = 1.85, 95% confidence interval [CI] 1.13–3.01) and hyperfiltration (OR = 2.28, 95% CI 1.03–5.09). However, upon further adjusting for uric acid, the association between the MHO phenotype and mildly reduced eGFR was reduced to null. Compared with MHNO/non-hyperuricemia, MHO/non-hyperuricemia was associated with an increased risk of mildly reduced eGFR (OR = 2.04, 95% CI 1.17–3.58), whereas MHO/hyperuricemia was associated with an observably increased risk (OR = 3.07, 95% CI 1.34–7.01).ConclusionsMHO was associated with an increased risk of early kidney dysfunction, and the serum uric acid partially mediated this association. Further prospective studies are warranted to clarify the causality.

Lipoprotein subclasses and early kidney dysfunction in young type 1 diabetes mellitus patients

Lipoprotein subclasses and early kidney dysfunction in young type 1 diabetes mellitus patients

Tangled relationship between insulin resistance and microalbuminuria in children with obesity.

Childhood obesity represents a complex disease with a well-known cardiometabolic burden including fatty liver, type 2 diabetes, metabolic syndrome, and cardiovascular disease. From a pathogenic point of view, insulin resistance (IR) represents the key factor underlying the spectrum of these obesity consequences. As observed in adults, recent data supported the occurrence of microalbuminuria (MA) as marker of early kidney dysfunction and its potential link with cardiometabolic factors also in children with obesity. In fact, a well-documented pathophysiological hypothesis both in adults and children supported an intimate correlation with the major feature of obesity such as IR through the influence of insulin on renal hemodynamics. Based on the clinical and prognostic relevance of this relationship in daily practice (including an increased risk of chronic kidney disease development overtime), more scientific attention needs to be paid to the evaluation of early kidney damage in children with obesity. In this paper, we attempt to address three debated questions regarding the intriguing liaison between IR and MA in children with obesity: (1) What is the prevalence of pediatric MA? (2) What is the state of art of MA in children with obesity? and (3) Is there a link between IR and MA in children with obesity?

Risk Prediction for Early Post-Donation Kidney Dysfunction in Live Kidney Donors Using a Common Data Model

Risk Prediction for Early Post-Donation Kidney Dysfunction in Live Kidney Donors Using a Common Data Model

Predictors of early renal dysfunction after heart transplantation: a report from the International Consortium on Primary Graft Dysfunction

Abstract Background Renal dysfunction is a common complication after heart transplantation (HT). Renal replacement therapy (RRT) after HT has been associated with increased risk of death. Long-term renal dysfunction is associated mainly to immunosuppressive therapy but is also strongly related to post-transplant renal failure. Predictors of early renal dysfunction after HT have not been clearly identified. Purpose We aimed to define predictors of early renal dysfunction after HT. Methods Our consortium includes 10 centers in the US, Canada and Europe. We collected data on all consecutive single-organ HT recipients from 2010 to 2020. The primary outcome was early renal dysfunction (ERD), defined as a composite of need for RRT or creatinine ≥2.5 mg/dL 24 hours after HT. We assessed the incidence of early renal dysfunction and performed univariate and multivariate analyses to identify the recipient and transplant characteristics associated with its development. Results We included 2,764 HT recipients: 282 (10.2%) presented early renal dysfunction and 2482 (89.8%) did not. Recipients who presented postoperative renal dysfunction were more frequently male, Caucasian, with previous sternotomy, higher baseline creatinine, longer ischemic time and worse donor LVEF. They were also more likely to be under RRT, intravenous inotropes or ECMO support and there was more incidence of severe primary graft dysfunction (PGD) (Table 1). Multi-variable logistic regression demonstrated that the strongest predictors for post-transplant renal dysfunction were development of severe PGD (OR 5.26, 2.88–9.62, p&amp;lt;0,001) and RRT prior to HT (OR 5.80, 2.93–11.5, p&amp;lt;0.001). Other predictors were male sex, previous sternotomy, long ischemic time and need for inotropes prior to HT. Conclusions Early renal dysfunction is a common complication after HT with an incidence around 10% in a large and contemporary cohort. The presence of PGD and need for RRT pre-transplant were the strongest predictors for its development. Interestingly, emergent transplantation or need for MCS were not independently associated with ERD. Further studies are needed to identify patients at high risk of early and late kidney dysfunction that may benefit from combined transplantation. Funding Acknowledgement Type of funding sources: None.

Cardiac Autonomic Nerve Dysfunction Predicts Incident Retinopathy and Early Kidney Dysfunction in Adolescents With Type 1 Diabetes.

Cardiac autonomic neuropathy (CAN) may contribute to vascular complications in diabetes. We hypothesized that adolescents with CAN are at greater risk of diabetic retinopathy and early kidney dysfunction. In this prospective longitudinal study of 725 adolescents with type 1 diabetes without retinopathy and albuminuria at baseline, early CAN was defined as one or more abnormalities in seven heart rate tests derived from a 10-min electrocardiogram. Retinopathy was defined as the presence of one or more microaneurysms, early kidney dysfunction as an albumin excretion rate (AER) >7.5 μg/min, and albuminuria as an AER >20 μg/min. Multivariable generalized estimating equations were used to examine the association between CAN and retinopathy or early kidney dysfunction. Cox proportional hazards regression analysis was used to assess cumulative risks of incident retinopathy and albuminuria. At baseline, the mean age of the sample was 13.6 ± 2.6 years, 52% were male, and mean diabetes duration was 6.1 ± 3.3 years. Over a median follow-up of 3.8 (interquartile range 2.2-7.5) years, the complication rate 27% for retinopathy, 16% for early kidney dysfunction, and 3% for albuminuria. The mean study HbA1c was 72.3 ± 16 mmol/mmol (8.6 ± 1.4%). CAN predicted incident retinopathy (odds ratio 2.0 [95% CI 1.4, 2.9]) and early kidney dysfunction (1.4 [1.0, 2.0]) after adjusting for HbA1c and diabetes duration. CAN also predicted retinopathy (hazard ratio 1.57 [95% CI 1.09, 2.26]) and albuminuria (2.30 [1.05, 5.04]) independently of HbA1c. CAN predicted incident retinopathy and kidney dysfunction in adolescents with type 1 diabetes, likely reflecting autonomic microvascular dysregulation contributing to complications. Therefore, screening and interventions to reduce CAN may influence the risk of complications.

Evaluation of kidney dysfunction in childhood cancer survivors

BackgroundThe major increase in the survival rate among children with cancer is due to improvement in the diagnosis and treatment. Despite this increase, childhood cancer survivors (CCS) are at high risk of developing late complications such as nephrotoxicity due to chemotherapy. So, we aimed to detect early subclinical kidney dysfunction among CCS.MethodsThis cross-sectional study was implemented on 52 survivors of childhood cancer recruited from Pediatric Oncology Unit, Menoufia University. Laboratory evaluations for each participant, including complete blood count, serum urea, creatinine, urinary protein, urinary calcium, uric acid, and serum cystatin C and urinary Neutrophil Gelatinase Associated Lipocalin (UrNGAL) by ELISA were obtained.ResultsEstimated GFR was decreased in 23.1% of cases, with elevated serum cystatin C, UrNGAL and UrNGAL/Cr. There was a significant increase of Uprotein/Cr, UCa/Cr, UACR (p = 0.02), UrNGAL and UrNGAL/Cr (P < 0.001) in patients with tubular dysfunction compared without tubular dysfunction. There was a significant difference between two groups regarding cisplatin (P = 0.03) and high-dose methotrexate chemotherapy (p = 0.04). The AUCs for detecting kidney tubular dysfunction by UrNGAL and UrNGAL/Cr were 0.807 and 0.747.ConclusionA significant tubular dysfunction among childhood cancer survivors receiving chemotherapy as cisplatin and high-dose methotrexate.ImpactDetection of kidney dysfunction mainly tubular in childhood cancer survivors after finishing chemotherapy.Urinary NGAL is a good predictor for detection of tubular dysfunction in childhood cancer survivors after finishing chemotherapy.

Clinical application of intraoperative somatic tissue oxygen saturation for detecting postoperative early kidney dysfunction patients undergoing living donor liver transplantation: A propensity score matching analysis.

BackgroundSomatic tissue oxygen saturation (SstO2) is associated with systemic hypoperfusion. Kidney dysfunction may lead to increased mortality and morbidity in patients who undergo living donor liver transplantation (LDLT). We investigated the clinical utility of SstO2 during LDLT for identifying postoperative kidney dysfunction.Patients and methodsData from 304 adults undergoing elective LDLT between January 2015 and February 2020 at Seoul St. Mary’s Hospital were retrospectively collected. Thirty-six patients were excluded based on the exclusion criteria. In total, 268 adults were analyzed, and 200 patients were 1:1 propensity score (PS)-matched.ResultsPatients with early kidney dysfunction had significantly lower intraoperative SstO2 values than those with normal kidney function. Low SstO2 (< 66%) 1 h after graft reperfusion was more highly predictive of early kidney dysfunction than the values measured in other intraoperative phases. A decline in the SstO2 was also related to kidney dysfunction.ConclusionsKidney dysfunction after LDLT is associated with patient morbidity and mortality. Our results may assist in the detection of early kidney dysfunction by providing a basis for analyzing SstO2 in patients undergoing LDLT. A low SstO2 (< 66%), particularly 1 h after graft reperfusion, was significantly associated with early kidney dysfunction after surgery. SstO2 monitoring may facilitate the identification of early kidney dysfunction and enable early management of patients.

Perioperative kidney injury in liver transplantation: a prospective study with renal histology and measured glomerular filtration rates

Background Acute kidney injury (AKI) is frequent after liver transplantation (LT), with impact on graft function, morbidity and mortality. Although multifactorial, the pathophysiology of perioperative kidney injury remains unclear. Our aims were to analyze the frequency, evolution and risk factors for kidney impairment during the peri- and early post-operative period. Methods In a prospective, single-center study of 27 adult patients undergoing first single-organ LT, we analyzed measured glomerular filtration rate (mGFR) pre-transplant, at post-operative day (POD) 10, and at 1, 3, 12 and 36 months. Kidney and liver graft biopsies were performed during LT. Results A median mGFR decline of 45% was detected from pre-transplant to POD 10, correlating strongly with the mGFR evolution from baseline to 12 months (rs = 0.80, p<.001) and baseline to 36 months (rs = 0.82, p<.001). AKI occurred in 59% of recipients within 48 h of LT, notably before the introduction of calcineurin inhibitors on POD 3. AKI was strongly associated with mGFR at 12 and 36 months. Kidney and liver graft biopsies showed only minor histological changes. Donor and recipient body mass index, recipient age, model of end-stage liver disease score, diagnosis of hepatitis C, donor cause of death, as well as bleeding, transfusions and duration of the anhepatic phase correlated with early kidney dysfunction. Conclusion The greatest decline in mGFR was evident within 10 days and AKI within hours of LT, irrespective of baseline mGFR and before introduction of calcineurin inhibitors. Very early post-LT kidney injury has substantial consequences for long-term kidney function.

Diet, obesity, and the gut microbiome as determinants modulating metabolic outcomes in a non-human primate model

BackgroundThe objective of this study was to increase understanding of the complex interactions between diet, obesity, and the gut microbiome of adult female non-human primates (NHPs). Subjects consumed either a Western (n=15) or Mediterranean (n=14) diet designed to represent human dietary patterns for 31 months. Body composition was determined using CT, fecal samples were collected, and shotgun metagenomic sequencing was performed. Gut microbiome results were grouped by diet and adiposity.ResultsDiet was the main contributor to gut microbiome bacterial diversity. Adiposity within each diet was associated with subtle shifts in the proportional abundance of several taxa. Mediterranean diet-fed NHPs with lower body fat had a greater proportion of Lactobacillus animalis than their higher body fat counterparts. Higher body fat Western diet-fed NHPs had more Ruminococcus champaneliensis and less Bacteroides uniformis than their low body fat counterparts. Western diet-fed NHPs had significantly higher levels of Prevotella copri than Mediterranean diet NHPs. Western diet-fed subjects were stratified by P. copri abundance (P. copriHIGH versus P. copriLOW), which was not associated with adiposity. Overall, Western diet-fed animals in the P. copriHIGH group showed greater proportional abundance of B. ovatus, B. faecis, P. stercorea, P. brevis, and Faecalibacterium prausnitzii than those in the Western P. copriLOW group. Western diet P. copriLOW subjects had a greater proportion of Eubacterium siraeum. E. siraeum negatively correlated with P. copri proportional abundance regardless of dietary consumption. In the Western diet group, Shannon diversity was significantly higher in P. copriLOW when compared to P. copriHIGH subjects. Furthermore, gut E. siraeum abundance positively correlated with HDL plasma cholesterol indicating that those in the P. copriLOW population may represent a more metabolically healthy population. Untargeted metabolomics on urine and plasma from Western diet-fed P. copriHIGH and P. copriLOW subjects suggest early kidney dysfunction in Western diet-fed P. copriHIGH subjects.ConclusionsIn summary, the data indicate diet to be the major influencer of gut bacterial diversity. However, diet and adiposity must be considered together when analyzing changes in abundance of specific bacterial taxa. Interestingly, P. copri appears to mediate metabolic dysfunction in Western diet-fed NHPs.6J_wxx79_1pf52UFxoCxzkVideo abstract

T-Cell Expression and Release of Kidney Injury Molecule-1 in Response to Glucose Variations Initiates Kidney Injury in Early Diabetes.

Half of the mortality in diabetes is seen in individuals <50 years of age and commonly predicted by the early onset of diabetic kidney disease (DKD). In type 1 diabetes, increased urinary albumin-to-creatinine ratio (uACR) during adolescence defines this risk, but the pathological factors responsible remain unknown. We postulated that early in diabetes, glucose variations contribute to kidney injury molecule-1 (KIM-1) release from circulating T cells, elevating uACR and DKD risk. DKD risk was assigned in youth with type 1 diabetes (n = 100; 20.0 ± 2.8 years; males/females, 54:46; HbA1c 66.1 [12.3] mmol/mol; diabetes duration 10.7 ± 5.2 years; and BMI 24.5 [5.3] kg/m2) and 10-year historical uACR, HbA1c, and random blood glucose concentrations collected retrospectively. Glucose fluctuations in the absence of diabetes were also compared with streptozotocin diabetes in apolipoprotein E -/- mice. Kidney biopsies were used to examine infiltration of KIM-1-expressing T cells in DKD and compared with other chronic kidney disease. Individuals at high risk for DKD had persistent elevations in uACR defined by area under the curve (AUC; uACRAUC0-10yrs, 29.7 ± 8.8 vs. 4.5 ± 0.5; P < 0.01 vs. low risk) and early kidney dysfunction, including ∼8.3 mL/min/1.73 m2 higher estimated glomerular filtration rates (modified Schwartz equation; Padj < 0.031 vs. low risk) and plasma KIM-1 concentrations (∼15% higher vs. low risk; P < 0.034). High-risk individuals had greater glycemic variability and increased peripheral blood T-cell KIM-1 expression, particularly on CD8+ T cells. These findings were confirmed in a murine model of glycemic variability both in the presence and absence of diabetes. KIM-1+ T cells were also infiltrating kidney biopsies from individuals with DKD. Healthy primary human proximal tubule epithelial cells exposed to plasma from high-risk youth with diabetes showed elevated collagen IV and sodium-glucose cotransporter 2 expression, alleviated with KIM-1 blockade. Taken together, these studies suggest that glycemic variations confer risk for DKD in diabetes via increased CD8+ T-cell production of KIM-1.

Early Kidney Dysfunction in Metabolic-Associated Fatty Liver Disease: Is Transient Elastography Useful as a Screening Method?

Introduction: Increasing evidence suggests an association between metabolic-associated fatty liver disease (MAFLD) and CKD. Timely prediction of early kidney dysfunction (EKD) is thus essential in this population although a screening method is not stablished. We aimed to evaluate the role of transient elastography (TE) in predicting EKD in patients with MAFLD. Materials and Methods: A prospective cohort study that included patients with MAFLD scheduled for evaluation was performed between May 2019 and January 2020. Demographic, clinical, and laboratory data and TE parameters were prospectively obtained. EKD was defined as microalbuminuria (urinary albumin-to-Cr ratio 30–300 mg/g) and estimated glomerular filtration rate ≥60 mL/min/1.73 m². Significant liver fibrosis was defined as liver stiffness measurement (LSM) ≥8.2 kPa. Results: Of the included 45 patients with MALFD, 53.3% were of female gender with mean age of 53.5 ± 10.9 years. EKD was found in 17.8% of patients. MAFLD patients with EKD were significantly more obese (BMI ≥30) (75.0 vs. 32.4%, p = 0.045) and had significantly higher LSM (8.5 ± 4.1 vs. 5.8 ± 2.2 kPa, p = 0.01). After adjustment of potential confounders for EKD, the presence of liver fibrosis remained a significant predictor of EKD, being associated with a 14.3-fold increased risk of EKD (p = 0.04). The optimal cutoff value of LSM to predict EKD was 6.1 kPa (sensitivity: 85.7%; specificity: 67.6%). Conclusion: Significant liver fibrosis is associated with a significant increased risk of EKD in patients with MAFLD, regardless of other comorbidities. Higher levels of LSM, particularly >6.1 kPa, alert for timely identification of EKD and associated comorbidities, as well as their control, in order to prevent the development of CKD in the long term.

Early Kidney Dysfunction after Liver Transplantation. Analysis of the Factors Involved in its Appearance and its Limpact on the Evolution of Patients

Purpose: Post-liver transplantation acute renal dysfunction is a poorly studied issue. We provide the results of an analysis, focused on identifying factors favoring its appearance, and analyzing the real impact of its development on the evolution of patients. Method: Observational single-center study carried out in a Spanish Liver Transplant Unit on a cohort of patients undergoing orthotopic liver transplantation from a cadaveric donor between May 2011 and October 2018. The presence of acute renal dysfunction (RIFLE criteria) was considered as a decrease in glomerular filtration rate (GFR) greater than 50% 48 hours after transplantation compared to the GFR immediately before transplantation. Results: Of 237 transplants performed, 172 met the inclusion criteria. They were mostly male patients (78%), with a median age and biological MELD score of 54 years and 15 points, respectively, and a prevalence of diabetes mellitus and arterial hypertension of 31 and 25%, respectively. The incidence of acute renal dysfunction was 29.7%, and the independent predictive factors for its development were pre-transplant arterial hypertension (Odds Ratio (OR) of 2.7), and pre-transplant deterioration of the recipient's liver function (OR 4,1). The development of acute renal dysfunction favors the appearance of early liver graft dysfunction according to the Olthoff et al criteria (p = 0.005). Although the survival at 3 and 6 months of the patient decreases (93.4 and 89.7% vs. 80 and 75%, respectively), and graft (90.9 and 87.9% vs. 80 and 75%, respectively), it does not alter the long-term survival of either of the two (p = 0.109 and 0.72, respectively). Conclusion: The factors that favor the appearance of early acute renal dysfunction after liver transplantation are arterial hypertension and the deterioration of liver function. Its establishment favors the development of early liver graft dysfunction and worsens patient and graft survival in the short and medium term, although it does not affect the long-term survival of both or kidney function.