With the constant need for technique improvement for ensuring correct diagnoses and precise treatment, imaging examinations that use contrast media have become unavoidable and indispensable. However, the long-term effects of contrast media on renal function remain unclear in populations with advanced renal failure. This study aimed to examine the relationship between contrast media exposure and long-term trends in renal function in patients with renal failure.
This retrospective cohort study included patients with a definitive diagnosis of chronic kidney disease who visited medical institutions in Japan between April 2012 and December 2020. The cohort was divided into contrast agent therapy and non-contrast agent therapy groups. The assessment indices were the number of contrast exposures and renal function decline. Renal function decline was calculated based on observed chronic kidney disease stage trends and glomerular filtration rate correspondence tables sourced from various guidelines. A stratified analysis focusing on changes in renal function while accounting for the acceleration of chronic kidney disease progression was also performed.
After adjusting for patient background with propensity score matching, 333 patients each were included in both groups. The observation period was 5.3 ± 2.1 and 4.9 ± 2.2 years per case in the contrast-enhanced and non-contrast-enhanced groups, respectively. The baseline estimated glomerular filtration rate at the beginning of the observation period was 55.2 ± 17.8 mL/min/1.73 m2 in the contrast-enhanced groups (P = 0.65). Although only slightly different in both groups, the glomerular filtration rate change was 1.1 ± 3.3 mL/min/1.73 m2/year in the contrast agent therapy group and tended to be higher with contrast media exposure. Stratified analysis showed that the annual glomerular filtration rate changes in patients with more contrast media exposures and altered renal function were 7.9 ± 7.1 mL/min/1.73 m2/year and 4.7 ± 3.6 mL/min/1.73 m2/year in the contrast agent therapy and non-contrast agent therapy groups, respectively (1.69 times, P < 0.05).
We were able to identify a clinical trend of successful measures for preventing adverse renal outcomes associated with contrast media exposure. However, increased frequency of contrast media exposure has a long-term effect on renal function in patients with altered it. Appropriate treatment choices related to contrast media may control chronic kidney disease.

OBJECTIVE: To compare the effect of glucose-lowering drugs on peripheral nerve and kidney function in prediabetes.
METHODS: Multicenter, randomized, placebo-controlled trial in 658 adults with prediabetes treated for 1 year with metformin, linagliptin, their combination or placebo. Endpoints are small fiber peripheral neuropathy (SFPN) risk estimated by foot electrochemical skin conductance (FESC < 70 μSiemens) and estimated glomerular filtration rate (eGFR).
RESULTS: Compared to the placebo, the proportion of SFPN was reduced by 25.1% (95% CI:16.3-33.9) with metformin alone, by 17.3% (95% CI 7.4-27.2) with linagliptin alone, and by 19.5% (95% CI 10.1-29.0) with the combination linagliptin/metformin (p < 0.0001 for all comparisons). eGFR remained +3.3 mL/min (95% CI: 0.38-6.22) higher with the combination linagliptin/metformin than with the placebo (p = 0.03). Fasting plasma glucose (FPG) decreased more with metformin monotherapy -0.3 mmol/L (95%CI: -0.48; 0.12, p = 0.0009) and with the combination metformin/linagliptin -0.2 mmol/L (95% CI: -0.37; -0.03) than with the placebo (p = 0.0219). Body weight (BW) decreased by -2.0 kg (95% CI: -5.65; -1.65, p = 0.0006) with metformin monotherapy, and by -1.9 kg (95% CI: -3.02; -0.97) with the combination metformin/linagliptin as compared to the placebo (p = 0.0002).
CONCLUSIONS: in people with prediabetes, a 1 year treatment with metformin and linagliptin, combined or in monotherapy, was associated with a lower risk of SFPN, and with a lower decrease in eGFR, than treatment with placebo.

Electrochemical fluorination manufacture of perfluorooctane sulfonic acid (PFOS), one of the most studied per- and polyfluoroalkyl substances, produces mixtures of linear and branched isomers, but little is known about human exposure to linear or branched PFOS isomers. We examined determinants affecting isomer-specific patterns of PFOS in serum in two adult populations in the United States, the National Health and Nutrition Examination Survey (NHANES) and the Study of Women\'s Health Across the Nation Multi-Pollutant Study (SWAN-MPS). After adjusting for demographic variables, fish consumption (in both populations), a glomerular filtration rate above 90 mL/min/1.73 m2 (observed in NHANES; not tested in SWAN-MPS), premenopausal status (only observed in SWAN-MPS), and less consumption of processed food (observed in SWAN-MPS; not tested in NHANES) were associated with a higher proportion of linear PFOS. Non-Hispanic Black and Asian participants were likely to have a higher proportion of linear PFOS than non-Hispanic White participants in both populations. Our findings suggest that isomer-specific patterns of PFOS serum concentrations in humans vary depending on population characteristics that affect PFOS exposure and excretion. Consideration of specific PFOS isomers in future human biomonitoring and epidemiologic studies can provide useful insight to better understand PFOS exposure.

Among complications of malnutrition secondary to anorexia nervosa (AN) or atypical anorexia nervosa (AAN), renal impairment remains poorly elucidated. Evaluating renal function in hospitalized pediatric patients with AN and AAN undergoing refeeding will yield important information to guide clinicians in screening and managing renal dysfunction in this population.
This is a secondary analysis of data from the Study of Refeeding to Optimize Inpatient Gains trial, a multicenter randomized clinical trial comparing higher calorie refeeding versus lower calorie refeeding in 120 adolescents and young adults hospitalized with medical instability secondary to AN or AAN. Baseline disease characteristics were obtained. Vital sign measurements, weight, electrolytes, and fluid status were evaluated daily to ascertain medical stability. Renal function on admission and throughout hospitalization was quantified using daily creatinine measurement and calculation of the estimated glomerular filtration rate (eGFR) using the modified Schwartz equation. Regression analysis and mixed linear models were utilized to evaluate factors associated with eGFR.
Of the 111 participants who completed treatment protocol, 33% had a baseline eGFR less than 90, suggesting renal impairment. Patients who experienced more rapid weight loss and more severe bradycardia were more likely to have low admission eGFR. While eGFR improved during refeeding, eGFR change by day based on refeeding treatment assignment did not reach statistical significance (95% confidence interval, -1.61, 0.15]; p = .095).
Renal impairment is evident on admission in a significant number of adolescents and young adults hospitalized with AN and AAN. We demonstrate that short-term medical refeeding yields improvement in renal function.

There is an increasing interest in using zebrafish (Danio rerio) larva as a vertebrate screening model to study drug disposition. As the pronephric kidney of zebrafish larvae shares high similarity with the anatomy of nephrons in higher vertebrates including humans, we explored in this study whether 3- to 4-day-old zebrafish larvae have a fully functional pronephron. Intravenous injection of fluorescent polyethylene glycol and dextran derivatives of different molecular weight revealed a cutoff of 4.4-7.6 nm in hydrodynamic diameter for passive glomerular filtration, which is in agreement with corresponding values in rodents and humans. Distal tubular reabsorption of a FITC-folate conjugate, covalently modified with PEG2000, via folate receptor 1 was shown. Transport experiments of fluorescent substrates were assessed in the presence and absence of specific inhibitors in the blood systems. Thereby, functional expression in the proximal tubule of organic anion transporter oat (slc22) multidrug resistance-associated protein mrp1 (abcc1), mrp2 (abcc2), mrp4 (abcc4), and zebrafish larva p-glycoprotein analog abcb4 was shown. In addition, nonrenal clearance of fluorescent substrates and plasma protein binding characteristics were assessed in vivo. The results of transporter experiments were confirmed by extrapolation to ex vivo experiments in killifish (Fundulus heteroclitus) proximal kidney tubules. We conclude that the zebrafish larva has a fully functional pronephron at 96 h postfertilization and is therefore an attractive translational vertebrate screening model to bridge the gap between cell culture-based test systems and pharmacokinetic experiments in higher vertebrates.NEW & NOTEWORTHY The study of renal function remains a challenge. In vitro cell-based assays are approved to study, e.g., ABC/SLC-mediated drug transport but do not cover other renal functions such as glomerular filtration. Here, in vivo studies combined with in vitro assays are needed, which are time consuming and expensive. In view of these limitations, our proof-of-concept study demonstrates that the zebrafish larva is a translational in vivo test model that allows for mechanistic investigations to study renal function.

BACKGROUND: Myocardial infarction with nonobstructive coronary arteries (MINOCA) constitutes about 10% of the cases of acute coronary syndromes (ACS). It is a working diagnosis and requires further diagnostics to determine the cause of ACS.
METHODS: In this study, 178 patients were initially diagnosed with MINOCA over a period of 3 years at the Department of Invasive Cardiology of the University Clinical Hospital in Białystok. The value of estimated glomerular filtration rate (eGFR) was calculated for all patients. The patients were divided into 2 groups depending on the value of eGFR: group 1-53 patients with impaired kidney function (eGFR < 60 mL/min/1.73 m2; 29.8%) and group 2-125 patients with normal kidney function (eGFR ≥ 60 mL/min/1.73 m2; 70.2%).
RESULTS: In group 1, the mean age of patients was significantly higher than that of group 2 patients (77.40 vs 59.27; p < 0.0001). Group had more women than group 2 (73.58% vs 49.60%; p = 0.003). Group 1 patients had higher incidence rate of arterial hypertension (92.45% vs 60.80%; p < 0.0001) and diabetes (32.08% vs 9.60%; p = 0.0002) and smoked cigarettes (22.64% vs 40.80%; p = 0.020). Group 1 patients had higher incidence rate of pulmonary edema, cardiogenic shock, sudden cardiac arrest (13.21% vs 4.00%; p = 0.025), and pneumonia (22.64% vs 6.40%; p = 0.001). After the 37-month observation, the mortality rate of the patients with MINOCA was 16.85%. Among group two patients, more of them became deceased during hospitalization (7.55% vs 0.80%; p = 0.012), followed by after 1 year (26.42% vs 7.20%; p = 0.0004) and after 3 years (33.96% vs 9.6%; p < 0.0001). Multivariate analysis revealed that the factors increasing the risk of death in MINOCA are as follows: older age, low eGFR, higher creatinine concentration, low left ventricular ejection fraction, and ST elevation in ECG.
CONCLUSIONS: Impaired kidney function is diagnosed in every third patient with MINOCA. Early and late prognosis of patents with MINOCA and renal dysfunction is poor, and their 3-year mortality is comparable to patients with myocardial infarction with significant stenosis of the coronary arteries and impaired kidney function.

Glomerular filtration (GF) and active tubular secretion (ATS) contribute to renal drug elimination, with the latter remaining understudied across the pediatric age range. Therefore, we systematically analyzed the influence of transporter ontogeny on the relative contribution of GF and ATS to renal clearance CLR for drugs with different properties in children. A physiology-based model for CLR in adults was extrapolated to the pediatric population by including maturation functions for the system-specific parameters. This model was used to predict GF and ATS for hypothetical drugs with a range of drug-specific properties, including transporter-mediated intrinsic clearance (CLint,T) values, that are substrates for renal secretion transporters with different ontogeny patterns. To assess the impact of transporter ontogeny on ATS and total CLR, a percentage prediction difference (%PD) was calculated between the predicted CLR in the presence and absence of transporter ontogeny. The contribution of ATS to CLR ranges between 41 and 90% in children depending on fraction unbound and CLint,T values. If ontogeny of renal transporters is < 0.2 of adult values, CLR predictions are unacceptable (%PD > 50%) for the majority of drugs regardless of the pediatric age. Ignoring ontogeny patterns of secretion transporters increasing with age in children younger than 2 years results in CLR predictions that are not systematically acceptable for all hypothetical drugs (%PD > 50% for some drugs). This analysis identified for what drug-specific properties and at what ages the contribution of ATS on total pediatric CLR cannot be ignored. Drugs with these properties may be sensitive in vivo probes to investigate transporter ontogeny.

OBJECTIVE: Therapeutic ultrasound (TUS) is one of the most commonly used modalities in low back pain treatment. The objective of this study was to determine whether TUS applied to the low back region in patients with chronic low back pain had any effect on renal function.
METHODS: Forty patients with chronic low back pain were randomized to 2 groups by a block randomization method. Thirty-seven patients completed the final evaluation. All patients were treated for 5 sessions per week for 3 weeks with the same physiotherapy modalities (superficial heating and transcutaneous electrical nerve stimulation) and exercise therapy; in addition to these treatments, the second group was treated with TUS for 10 minutes (frequency, 1 MHz; intensity, 1.5 W/cm2 ; and effective irradiation area of the transducer head, 5 cm2 ). The serum creatinine, serum cystatin C, 24-hour urine creatinine, creatinine clearance, 24-hour urine microalbumin and microprotein, urine volume, and glomerular filtration rate were measured. The patients were evaluated at baseline (day 0) and the end of the treatment (day 21).
RESULTS: The serum cystatin C levels were increased in both groups, but this increase was not significant (P > .05). There was no difference between the groups in the percent change in all outcome measures (P > .05).
CONCLUSIONS: This showed that TUS applied to the low back region does not affect renal function.

The purpose of this review is to correlate predictions based on pre-clinical data with outcomes from clinical trials that examine the effects of incretin-based diabetes treatments on the kidney. The incretin-based treatments include agonists of the glucagon-like peptide 1 receptor (GLP-1R) and inhibitors of the enzyme, dipeptidyl peptidase-4 (DPP-4). In addition, what is known about the incretin-based therapies will be compared to what is known about the renal effects of SGLT2 inhibitors.
Large-scale clinical trials have shown that SGLT2 inhibitors reduce albuminuria and preserve estimated glomerular filtration rate (eGFR) in patients with diabetic nephropathy. A concise and plausible hemodynamic mechanism is supported by pre-clinical research on the physiology and pharmacology of SGLT2. Large-scale clinical trials have shown that incretin-based therapies mitigate albuminuria but have not shown beneficial effects on eGFR. Research on the incretin-based therapies has yielded a diverse array of direct effects throughout the body, which fuels speculation as to how these drugs might benefit the diabetic kidney and affect its function(s). But in vivo experiments have yet to confirm that the proposed mechanisms underlying emergent phenomena, such as proximal tubular fluid reabsorption, are the ones predicted by cell and molecular experiments. There may be salutary effects of incretin-based treatments on the diabetic kidney, but the system is complex and not amenable to simple explanation or prior prediction. This contrasts with the renal effects of SGLT2 inhibitors, which can be explained concisely.

OBJECTIVE: Although primarily a mental health disorder, anorexia nervosa (AN) has many physical consequences. Among them, the consequences on kidney function are often underestimated. We evaluated renal function in adolescent AN inpatients and investigated the correlation between the GFR and intrinsic patient characteristics.
METHODS: A single-center retrospective study was conducted on 51 patients hospitalized for the restrictive type of AN in 2013. Data were divided into: (1) medical history of AN; (2) growth parameters and vital signs upon admission; and (3) blood tests. The glomerular filtration rate (GFR) was calculated using the Cockroft-Gault, MAYO Clinical Quadratic (MCQ), Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI), the Modification of Diet in Renal Disease (MDRD), and Schwartz equations.
RESULTS: The calculated percentages of patients with a GFR below 90 mL/min/1.73 m2 according to the different equations were as follows: Cockroft-Gault, 45%; MDRD, 28%; CKD-EPI, 14%; MCQ, 12%, and Schwartz, 4%. There was a strong association between the body mass index (BMI) and the GFR according to all equations (p < 0.0001). The lowest heart rate was significantly associated with a reduced GFR according to the Cockroft-Gault equation (p = 0.03). The GFR values did not differ significantly after rehydration.
CONCLUSIONS: Clinicians should evaluate AN patients for renal complications, especially when the BMI and heart rate are very low. Dehydration was not solely responsible for renal impairment.
METHODS: Level III, single-center retrospective cohort study.