Altered Kidney Function Research Articles

Long-term effects of IVF on offspring kidneys: observations from adolescence to adulthood

Research questionWhat is the effect of in-vitro fertilization (IVF) on long-term health of offspring kidney? DesignWe established an IVF mouse model and subsequently observed renal structure, function, and cortical oxidative stress from the age of 2 months to ascertain any disparities compared to natural conceived (NC) offspring. And this kind of process continued until the mice reached 5 months old. ResultsWe found no significant difference in the body weight of mice aged 2 to 5 months between IVF and NC offspring. However, the renal/weight ratio of IVF offspring was higher than that of NC offspring at 2 months and 3 months, but this difference disappeared in offspring aged 4 to 5 months. IVF offspring at 5 months of age had lower urine creatinine (Ucr) levels compared to NC offspring. Moreover, The expression of ACE2 was observed to decrease in the kidneys of 4 to 5-month-old IVF mice, and the expression of AGTR1A was higher in 5-month-old IVF mice compared to NC mice. The malondialdehyde (MDA) level in 5-month-old IVF offspring was higher than in NC offspring. ConclusionOur study indicated that microvascular thickness in the kidneys of IVF offspring remains unchanged, but minor alterations in kidney function, RAS gene expression, and renal cortical oxidative stress were evident by 5 months of age.

Early metabolic and hemodynamic indicators of kidney dysfunction in mice offspring from parental low protein diet

BackgroundParental malnutrition, particularly a low-protein diet (LPD), causes oligonephropathy at birth and predisposes offspring to hypertension and chronic kidney disease later in life. The onset of adult kidney disease varies based on genetics and environmental factors, often with subclinical alterations in kidney function being overlooked. This study aimed to examine changes in kidney morphology before significant kidney function decline in the offspring of mice fed a low-protein diet.MethodsUsing a combination of histological analysis, kidney metabolic and hemodynamic panel assessments, and advanced statistical techniques such as Linear Discriminant Analysis (LDA) and Principal Component Analysis (PCA), we investigated the initial impact of a maternal low-protein diet (LPD) on kidney development and function. Our study utilized 12-week-old F1 mice from F0 parents fed either a low-protein diet (LPD) or a normal-protein diet (NPD) before the onset of hypertension.ResultsThe offspring (F1 generation) of parents (F0 generation) fed an LPD show reduced body weight from birth to P20. The kidney weight was also reduced compared to F1 offspring from parents fed an NPD. At 12 weeks of age, body weight normalized, but kidney weight remained low. Offspring of parents fed an LPD displayed abnormal kidney morphology, including dilated tubules, oligonephropathy, and fluid-filled cysts which had worsened with age. A kidney metabolic panel analysis at 12 weeks revealed a slight but consistent increase in urine albumin, plasma creatinine, mean urea, and BUN concentrations. Although no significant changes in hemodynamic variables were observed, 2/12 mice, both males, showed alterations in systolic blood pressure, suggesting sex-specific effects when comparing F1 mice from F0 fed either diet. Overall, kidney metabolic changes were strongly correlated to parental LPD.ConclusionOur findings indicate that significant kidney damage must accumulate in the F1 generation from parents fed an LPD before any detectable changes in blood pressure occur. Our study suggests that small variations in kidney metabolic function may point to early kidney damage and should not be overlooked in the offspring of these malnourished mice and likely humans.

Thyroid, neurodevelopmental, and kidney toxicities of common organic UV filters in embryo-larval zebrafish (Danio rerio), and their potential links

Organic UV filters (OUVFs) have been commonly used in sunscreen and many consumer products. Following dermal application, these compounds can enter circulation and may cause systemic effects in humans. In the present study, we chose four OUVFs frequently detected in the environment, i.e., avobenzone (AVB), benzophenone-3 (BP-3), octocrylene (OC), and octyl methoxycinnamate (OMC), and evaluated their thyroid, neurodevelopmental, and kidney toxicities. For this purpose, zebrafish embryos (<4 h post fertilization, hpf) were exposed to sublethal concentrations of AVB, BP-3, OC, or OMC until 120 hpf. Exposure to all OUVFs decreased thyroid hormone (TH) levels, probably by enhanced metabolism and excretion of THs (ugt1ab and/or sult1 st5) in the larval fish. Exposure to the OUVFs also induced hypoactivities and/or anxiety-like behaviors: Regulatory changes of mbp, gfap, c-fos, syn2a, sty1a, and stxbp1b genes, support the changes in normal neurobehavior of the larval fish. Moreover, the OUVFs exposure caused increased proteinuria in the fish, along with transcriptional changes of wt1, nephrin, podocin, and cdh17 genes, which could explain the observed reduction in kidney functions. Principal component analysis (PCA) implied the potential interplay of THs with neurogenesis, or podocyte differentiation of the larval fish. Toxicological consequences of altered TH homeostasis, neurobehavior, and kidney function at the early life stage warrant further investigations not only in humans but also in aquatic ecosystems.

Harnessing Nitric Oxide-Donating Benzofuroxans for Targeted Inhibition of Carbonic Anhydrase IX in Cancer.

We describe here the design and antitumor evaluation of benzofuroxan-based nitric oxide (NO)-donor hybrid derivatives targeting human carbonic anhydrases (hCAs) IX and XII. The most effective compounds, 27 and 28, demonstrated potent dual action, exhibiting low nanomolar inhibition constants against hCA IX and significant NO release. Notably, compound 27 showed significant antiproliferative effects against various cancer cell lines, particularly renal carcinoma A-498 cells. In these cells, it significantly reduced the expression of CA IX and iron-regulatory proteins, inducing apoptosis via mitochondrial caspase activity and ferroptosis pathways, as evidenced by increases in ROS, nitrite, and down-regulated expression of ferritin-encoding genes. In three-dimensional tumor models, compound 27 effectively reduced spheroid size and viability. In vivo toxicity studies in mice indicated that the compounds were well-tolerated, with no significant alterations in kidney function. These findings underscore the potential of benzofuroxan-based CA inhibitors for further preclinical evaluations as therapeutic agents targeting renal cell carcinoma.

Identification of risk factors for adverse drug events in a general hospital.

Adverse events (AEs), and particularly adverse drug events (ADEs), represent a health problem as they can cause permanent damage or death. Understanding the frequency, location, and causes of ADEs can prevent harm to patients. The Global Trigger Tool, produced by the Institute for Healthcare Improvement (GTT/IHI), is widely used to identify AEs. Recognizing the profile of patients who suffer ADEs can reveal clinical or individual characteristics that predispose to the occurrence of AEs. A cross-sectional study was carried out through a retrospective analysis of 120 medical charts of patients discharged from hospital between October 2020 and April 2021. Patients over 18 years old, with a length of stay of more than 24 h, were included. The list of triggers used was from the medication module of the GTT/IHI, which was adapted for use in the institution. Two primary reviewers and a medical reviewer applied this tool. The primary reviewers independently assessed the randomized charts. A meeting to achieve consensus among the reviewers was held every 2 weeks to validate the identified ADEs; classifications were based on harm severity. Multivariate logistic regression was utilized to assess the variables that predicted the occurrence of ADEs, using the backward stepwise method. A total of 43 ADEs were identified, with a frequency of 36 per 100 admissions (43/120). Of these, five ADEs (12%) were responsible for patients being admitted to hospital. In the case of in-hospital ADEs, there were 42.2 per 1000 patients/day. The clinical manifestation of altered kidney function (16%) and the anatomical drug group of the nervous system (33%) were the most frequent ADEs. The multivariate logistic regression model was significant (×2 = 44.960, P < .001), indicating that factors such as: known drug allergy [odds ratio 5.728; 95% confidence interval (CI): 1.249, 26.274, P = .025]; being clinically hospitalized (odds ratio 7.504; 95% CI: 1.654, 34.037; P = .009); number of medicines used (odds ratio 1.100; 95% CI: 1.054, 1.148; P < .001); and being under the care of internal medicine (odds ratio 3.633; 95% CI: 1.257, 10.511; P = .017) were predictor variables associated with the occurrence of ADEs. A significant percentage of hospitalized patients experienced at least one ADE, with rates surpassing those found in similar studies. The GTT/IHI effectively assessed medication-related harm, emphasizing the need for tailored triggers based on population characteristics. Predictor variables can inform preventive strategies. Overall, the tool facilitated a localized risk assessment of medication use.

Does Age Influence Immunosuppressant Drug Pharmacokinetics in Kidney Transplant Recipients?

The pharmacokinetics of immunosuppressant drugs may change with advancing age, potentially affecting patient outcomes. To characterise the effects of age on the pharmacokinetic and exposure parameters of tacrolimus, mycophenolate, and prednisolone. Pharmacokinetic profiling, involving whole blood tacrolimus, total and free plasma mycophenolic acid (MPA), total plasma mycophenolic acid glucuronide (MPAG), and total and free plasma prednisolone, was performed in an older and younger adult cohort. Thirteen samples were drawn on a single occasion, pre-oral dose and then at 0.25, 0.5, 0.75, 1, 1.25, 1.5, 2, 3, 4, 6, 9, and 12h post-dose. Non-compartmental analysis was conducted using the PKNCA package, and pharmacokinetic and exposure parameters were compared between age groups using a Mann-Whitney test. A regression analysis was conducted for free MPA and MPAG using significant variables of interest. This exploratory study included 21 older and 18 younger adults. Dose-adjusted tacrolimus, total MPA and free prednisolone pharmacokineticparameters were not different between age groups; however, for free MPA and MPAG, older recipients had significantly greater minimum and maximum concentrations, trough concentrations, and half-life. There was a two-fold increase in free MPA exposure in older adults (median dose-adjusted AUC0-12: 1284 vs. 684μgh/L, p<0.0001); MPAG exposure similarly increased. Age was significantly associated with free MPA and MPAG exposure, and free MPA exposure was associated with haematocrit (p<0.05). Differences in MPA were found with advancing age and may be due to altered kidney function, haematocrit, plasma protein binding and/or drug absorption. Future research should explore specific covariate contributions to this further.

Purinergic Receptor Antagonists: A Complementary Treatment for Hypertension.

The treatment of hypertension has improved in the last century; attention has been directed to restoring several altered pathophysiological mechanisms. However, regardless of the current treatments, it is difficult to control blood pressure. Uncontrolled hypertension is responsible for several cardiovascular complications, such as chronic renal failure, which is frequently observed in hypertensive patients. Therefore, new approaches that may improve the control of arterial blood pressure should be considered to prevent serious cardiovascular disorders. The contribution of purinergic receptors has been acknowledged in the pathophysiology of hypertension; this review describes the participation of these receptors in the alteration of kidney function in hypertension. Elevated interstitial ATP concentrations are essential for the activation of renal purinergic receptors; this becomes a fundamental pathway that leads to the development and maintenance of hypertension. High ATP levels modify essential mechanisms implicated in the long-term control of blood pressure, such as pressure natriuresis, the autoregulation of the glomerular filtration rate and renal blood flow, and tubuloglomerular feedback responses. Any alteration in these mechanisms decreases sodium excretion. ATP stimulates the release of vasoactive substances, causes renal function to decline, and induces tubulointerstitial damage. At the same time, a deleterious interaction involving angiotensin II and purinergic receptors leads to the deterioration of renal function.

The components of arginine and methylarginine metabolism are indicative of altered kidney function in intrauterine growth-restricted neonates.

Intrauterine fetal growth restriction (IUGR) affects up to 10% of all pregnancies. Severe IUGR is associated with impaired kidney development, reduced nephron endowment, and chronic kidney disease later in life. Currently, no early predictive biomarker exists for detecting altered kidney function in neonates with IUGR. Because nephrons produce key enzymes for the metabolism of arginine and methylarginine components, we quantified and compared the concentrations of arginine and methylarginine metabolites between IUGR and non-IUGR neonates to identify potential biomarkers for the early detection of altered kidney function in IUGR neonates. Seventy-one IUGR and 123 non IUGR neonates were examined. Serum and Urine samples were obtained between 30 h and 5 days of life and between 5 and 70 days of life. Serum concentrations of creatinine, urea, symmetric and asymmetric-dimethylarginine metabolites (SDGV, SDMA, ADGV, and ADMA), guanidino-2-oxo-caproic acid (GOCA), citrulline, homocitrulline, arginine, and homoarginine were quantified using LC-MS/MS and standard clinical laboratory methods. Datasets were compared by Mann-Whitney--Wilcoxon or Chi-square tests for continuous and discrete parameters. P values were corrected for multiple comparisons using the Bonferroni method. After Bonferroni correction, we found that serum creatinine, urea, SDGV, ADGV, and GOCA levels were significantly lower in neonates with IUGR. Consequently, the ratios of SDGV/SDMA, ADGV/ADMA, and GOCA/homoarginine were significantly lower in IUGR neonates. Our study suggests that arginine and methylarginine are possible early biomarkers for detecting altered kidney function in IUGR neonates.

Nuclear factor erythroid 2-related factor 2 activation in streptozotocin-induced diabetic rats normalize renal hemodynamics and oxygen consumption.

Diabetic kidney disease is a major contributor to end stage renal disease. A change in kidney oxygen homeostasis leading to decreased tissue oxygen tension is an important factor initiating alterations in kidney function in diabetes. However, the mechanism contributing to changed oxygen homeostasis is still unclear. Hyperglycemia-induced production of reactive oxygen species and an altered response to them have previously been demonstrated. In the present study, chronic treatment with DL-sulforaphane to induce nuclear factor erythroid 2-related factor 2 (Nrf2) expression, a master transcriptional regulator binding to antioxidant response elements inducing increased protection against reactive oxygen species, is studied. Sprague-Dawley rats were made diabetic using streptozotocin and either left untreated or received daily subcutaneous injections of DL-sulforaphane for 4 weeks. Age-matched non-diabetic rats served as controls. After 4 weeks of treatment, rats were anesthetized using thiobutabarbital, and kidney functions were studied in terms of glomerular filtration rate (GFR), renal blood flow (RBF), sodium transport, kidney oxygen consumption, and kidney oxygen tension. Mitochondria was isolated from kidney cortical tissue and investigated using high-resolution respirometry. GFR was increased in diabetics but not RBF resulting in increased filtration fraction in diabetics. DL-sulforaphane treatment did not affect RBF and GFR in controls but decreased the same parameters in diabetics. Increased GFR resulted in increased sodium transport and oxygen consumption, hence decreased efficiency in diabetics compared to controls. Increased oxygen consumption in diabetics resulted in decreased cortical tissue oxygen tension. DL-sulforaphane treatment decreased oxygen consumption in diabetics, whereas transport efficiency was not significantly affected. DL-sulforaphane treatment increased cortical pO2 in diabetics. DL-sulforaphane treatment affects renal hemodynamics, improving cortical oxygen tension but not mitochondrial efficiency.

#2317 Did acute kidney injury confer greater mortality in COVID-19 hospitalized patients? A Portuguese hospital experience in the third COVID wave

Abstract Background and Aims The outbreak of coronavirus disease 2019 (COVID-19) pandemic, which originated in December 2019, had a huge impact on healthcare worldwide. Numerous studies have reported alterations in kidney function among hospitalized patients with COVID-19, such as hematuria, proteinuria, and acute kidney injury (AKI). Histopathology exams in autopsies have identified various potential causes for the presence of AKI in these patients, with reports linking AKI to unfavorable outcomes across multiple countries. However, additional data concerning hospitalized COVID patients in Portugal are essential to further understand this aspect. Method Retrospective cohort study enrolling adult patients, who attended the Emergency Department and recorded positive polymerase chain reaction (PCR) results for SARS-CoV-2 from January 1 to January 31, 2021. AKI was diagnosed using the Kidney Disease Improving Global Outcome (KDIGO) classification based on serum creatinine (sCr) criteria and using a background creatinine available in the patient record. We performed an analysis of incidence, lethality, and possible risk factors of AKI in COVID-19 patients. Results The study encompassed a cohort of 239 patients, of whom 62 (25.94%) received a diagnosis of Acute Kidney Injury (AKI) based on KDIGO criteria. Within this subgroup, the average age was 77.65 years (±12.07), with a total of 29 male patients (46.78%). Notably, 30 deaths (48.39%) occurred during the hospital stay in this group. Regarding the AKI classification, 39 patients (62.9%) were classified as KDIGO-AKI stage 1, 14 patients (22.58%) as stage 2, and 9 patients (14.52%) as stage 3. Regarding the timing of the diagnosis of AKI, 54 (87%) occurred in the moment of admission, 7 patients (11.3%) were diagnosed within the first 48 hours and a solitary case (1.6%) was diagnosed after 7 days of hospitalization. In the non-AKI group, the mean age was 69.86 years (±15.95), and approximately 55% were male. Within this group, 49 deaths (27.7%) were recorded during hospitalization. Significantly higher mortality rates were observed in the AKI group, demonstrating a statistically significant difference (p &amp;lt; 0.01) and a relative risk of 1.75 or mortality during hospitalization for AKI patients. Furthermore, the duration of hospitalization was notably prolonged in the AKI group (p &amp;lt; 0.01), with a disparity of approximately three days. Individuals who developed AKI exhibited lower scores on the Barthel-dependence scale, indicative of higher dependence (p &amp;lt; 0.01), and were significantly older (p &amp;lt; 0.01) comparing with the ones that did not develop acute kidney injury. Additionally, it was remarkable that the leukocyte count at admission was more elevated in the AKI group (p = 0.03) compared to non-AKI patients with a difference of approximately 1.62×109/L. Conclusion Respiratory infections, including COVID-19, frequently lead to emergency department admissions and hospitalizations. This study validates an elevated prevalence of acute kidney injury (AKI) both at admission and during the hospital stay in such cases. The presence of AKI is linked to adverse outcomes, including mortality and extended hospital stays, underscoring the critical importance of promptly diagnosing AKI. Larger-scale studies are warranted in this field to enhance our understanding of this entity and therefore improve the outcomes related to this prevalent condition.

Kidney Function Tests and Continuous eGFR Decrease at Six Months after SARS-CoV-2 Infection in Patients Clinically Diagnosed with Post-COVID Syndrome.

The long-term sequelae of SARS-CoV-2 infection are still under research, since extensive studies showed plenty of systemic effects of the viral infection, extending even after the acute phase of the infection. This study evaluated kidney function tests six months after SARS-CoV-2 infection in patients clinically diagnosed with Post-COVID Syndrome, hypothesizing persistent renal dysfunction evidenced by altered kidney function tests compared to baseline levels. Continuous eGFR decrease <30 at six months post-infection was considered the main study outcome. Conducted at the "Victor Babes" Hospital, this retrospective observational study involved adults with laboratory-confirmed SARS-CoV-2 infection and clinically-diagnosed Post-COVID Syndrome, excluding those with prior chronic kidney disease or significant renal impairment. Kidney function tests, including serum creatinine, blood urea nitrogen (BUN), estimated glomerular filtration rate (eGFR), alongside markers of kidney damage such as proteinuria and hematuria, were analyzed. Among 206 participants, significant differences were observed between the control (n = 114) and the Post-COVID group (n = 92). The Post-COVID group exhibited higher serum creatinine (109.7 μmol/L vs. 84.5 μmol/L, p < 0.001), lower eGFR (65.3mL/min/1.73 m2 vs. 91.2 mL/min/1.73 m2, p < 0.001), and elevated BUN levels (23.7 mg/dL vs. 15.2 mg/dL, p < 0.001) compared to the control group. Regression analysis highlighted significant predictors of continuous eGFR decrease <30 at six months post-infection. The development of acute kidney injury (AKI) during the initial COVID-19 illness emerged as a strong predictor of reduced eGFR (β = 3.47, p < 0.001). Additional factors, including a creatinine increase (23 μmol/L above the normal range) and an elevated Albumin to Creatinine Ratio (ACR) (>11 mg/g above the normal range), were significantly associated with eGFR reduction. Patients with Post-COVID Syndrome demonstrate significant renal impairment six months post-SARS-CoV-2 infection. The study's findings stress the need for ongoing monitoring and intervention strategies for renal health in affected individuals, underscoring the persistent impact of COVID-19 on renal function.

Association between Polycystic Ovarian Syndrome, Impaired Kidney Function and Hyperuricaemia: A Systematic Review and Meta-analysis.

Polycystic ovarian syndrome (PCOS) is a gynaecological problem affecting women within reproductive age, accompanied by several metabolic anomalies, thus leading to alteration in kidney function and hyperuricaemia. Due to the high prevalence of cardiometabolic factors in PCOS, there is a need to anticipate an increased number of kidney impairments amongst these women. This review aims to investigate the potential link between PCOS, impaired kidney function, and elevated uric acid levels. By elucidating this association, we hope to provide clinicians with a tool to stratify the risk of kidney disease in women diagnosed with PCOS, based on readily available kidney function parameters. The recommendations used for the analysis were outlined in the Preferred Reporting Items for Systematic Reviews and Meta-Analyses 2020 guidelines. Subsequently, eligible studies were identified using several databases (MEDLINE, ProQuest and EBSCOhost) between 1996 and 2022, with a total of 13 studies included. Serum uric acid, serum creatinine, as well as estimated glomerular filtration rate (eGFR) were evaluated as the outcome of interest. Quality assessment for cohort, case-control and cross-sectional studies was conducted utilising the Newcastle-Ottawa Scale, while Review Manager 5.4 was utilised for meta-analysis. Uric acid was significantly higher in women with PCOS (mean difference [MD] = 0.70, 95% confidence interval [CI] [0.45-0.95], P < 0.00001). Meanwhile, serum creatinine and eGFR were statistically similar in each group (MD = 0.08, 95% CI [-0.05-0.21], P = 0.22 and MD = 3.54, 95% CI [-4.53-11.61], P = 0.39, respectively). This review showed that PCOS was significantly associated with elevated uric acid. However, no significant difference was found between eGFR and creatinine levels compared to healthy controls. Routine uric acid assessment in PCOS patients is recommended as a simple tool for risk stratification. No body mass index (BMI) subgroup analysis was done due to limited BMI reporting in our included studies. Quantitative analysis of all kidney function parameters was also limited by sparse data on urea and albumin. CRD42023410092 (02 April 2023).

Cystatin C Outperforms Creatinine in Predicting Cefepime Clearance in Pediatric Stem Cell Transplant Recipients

BackgroundPediatric hematopoietic stem cell transplant (HSCT) patients are at risk of developing both sepsis and altered kidney function. Cefepime is used for empiric coverage post-HSCT and requires dose adjustment based on kidney function. Since cefepime's anti-microbial efficacy is determined by the time free concentrations exceed bacterial minimum inhibitory concentration (MIC), it is important to assess kidney function accurately to ensure adequate concentrations. Serum creatinine (SCr) is routinely used to estimate glomerular filtration rate (eGFR) but varies with muscle mass, which can be significantly lower in HSCT patients, making SCr an inaccurate kidney function biomarker. Cystatin C (CysC) eGFR is independent of muscle mass, though steroid use increases CysC. ObjectivesTo describe how eGFR impacts cefepime pharmacokinetic/pharmacodynamic (PK/PD) target attainment in pediatric HSCT patients, to investigate which method of estimating GFR (SCr, CysC, combined) best predicts cefepime clearance, and to explore additional predictors of cefepime clearance. Study DesignPatients admitted to the pediatric HSCT unit who received ≥2 cefepime doses were prospectively enrolled. We measured total cefepime peak/trough concentrations between the 2nd-4th cefepime doses and measured SCr and CysC if not already obtained clinically within 24h of cefepime samples. eGFRs were calculated with Chronic Kidney Disease in Children U25 equations. Bayesian estimates of cefepime clearance were determined with a pediatric cefepime PK model and PK software MwPharm++. Simple linear regression was used to compare cefepime clearance normalized to body surface area (BSA) to BSA-normalized SCr-, CysC-, and SCr-/CysC-eGFRs, while multiple linear regression was used to account for additional predictors of cefepime clearance. For target attainment, we assessed the percentage of time free cefepime concentrations exceeded 1x MIC (%fT>1x MIC) and 4x MIC (%fT>4x MIC) using a susceptibility breakpoint of 8 mg/L for Pseudomonas aeruginosa. ResultsWe enrolled 53 patients (ages 1-30 years, median 8.9 years). SCr- and CysC-eGFRs were lower in patients who attained 100% fT>1xMIC compared to those who did not attain this target: 115 vs 156 mL/min/1.73m2 (p=0.01) for SCr-eGFR and 73.5 vs 107 mL/min/1.73m2 (p<0.001) for CysC-eGFR. SCr-eGFR was weakly positively correlated with cefepime clearance (adjusted [a]r2=0.14), while CysC-eGFR and SCr-/CysC-eGFR had stronger positive correlations (ar2=0.30 CysC, ar2=0.28 combo. There was a weak, significant linear association between increasing CysC-eGFR and decreased %fT>1xMIC (ar2=0.32) and %fT>4xMIC (ar2=0.14). No patients with a CysC-eGFR >120 mL/min/1.73 m2 achieved 100% fT>1xMIC or 50% fT>4x MIC. In multiple regression models, underlying diagnosis of hemoglobinopathy (in all models) and being pre-transplant (in SCr and combined models) were associated with increased cefepime clearance, while concomitant use of calcineurin inhibitors was associated with decreased cefepime clearance in all models. Overall, the combo-eGFR model with timing pre-transplant, hemoglobinopathy, and use of calcineurin inhibitors had the best performance (ar2=0.63). ConclusionsCysC-based eGFRs (CysC alone and combined) predicted cefepime clearance better than SCr-eGFR, even after considering steroid use. Increasing CysC eGFR correlated with decreased probability of PD target attainment, raising concerns for underdosing at high eGFRs. CysC should be included when estimating kidney function to provide adequate dosing of cefepime in pediatric HSCT patients.

A comprehensive analysis of albuminuria in canine chronic kidney disease.

Albuminuria, an important marker of decreased kidney function in chronic kidney disease (CKD), is not routinely used for CKD detection or proteinuria appearance. Its relationships with biochemical parameters and blood pressure in dogs are poorly understood. This study aimed to evaluate the relationship of albuminuria with various CKD markers, its correlation with the urinary protein to creatinine ratio (UPC), and hypertension in dogs with early stages of CKD. It also sought to determine the usability of the urinary albumin to creatinine ratio (UAC) for CKD screening. The study reviewed records of 102 dogs, categorising them into four groups based on disease status. UAC and UPC ratio, biochemistry and haematology variables, age, and systolic blood pressure were determined. The Pearson's correlation coefficient between log-transformed values of UPC and UAC was r = 0.902 (95% CI: 0.87 to 0.93). Median UAC ratio values were 2.1mg/g for the Healthy control group (n = 17), 54.2mg/g for early stages CKD (n = 42), 5.8mg/g for Acute sick control (n = 30), and 104mg/g for Chronic sick control (n = 13). Thresholding UAC ratio as an indicator for impaired kidney function with the threshold of 10mg/g (established based on the receiver operating characteristic curve) had a sensitivity 81.8%, specificity of 89.4%, positive predictive value (PPV) 90%, and negative predictive value (NPV) 80.1%. The correlation of UAC with biochemistry and haematology variables was statistically significant; for SDMA (μg/L), it was r = 0.566 and for other variables, it was weak to moderate. UAC was markedly elevated in cases of severe hypertension. UAC ratio was significantly different among dogs with impaired and not impaired kidney function. The correlation strength for the UAC and UPC ratios was high. UAC ratio may be a promising marker for proteinuria analysis in dogs with CKD or other kidney function alterations.

Exploration of tumor growth regression of quinoa and chia oil nanocapsules via the control of PIK3CA and MYC expression, anti-inflammation and cell proliferation inhibition, and their hepatorenal safety in rat breast cancer model

BackgroundThe second most common cancer in the world is breast cancer. Chemotherapy is used to treat breast cancer, but instances of multidrug resistance, targets that are not selective, and physicochemical issues raise doubts about its efficacy. So, the exploration of chemopreventive agents from efficient natural sources has been required. The chia and quinoa seeds have health-promoting activities that include cardio-protective, antidiabetic, and anticancer effects. Given the paramount importance of their oils and their potential bioactivities, this work aimed to assess the repressive effect of their oil nanocapsules against mammary tumors in rats. Rat models of chemically induced mammary tumors were gavaged with chia and quinoa nanocapsules for one month. The repressive effect of nanocapsules was studied by quantifying TNF-α, assessing the gene expression of proto-oncogenes (PIK3CA and MYC) using qRT-PCR, and analyzing the cell cycle in mammary tissue.ResultsThe studies clarified that the inhibition of tumors in response to quinoa and chia nanocapsules was associated with a reduction in TNF-α levels, proliferation capability, and motivation for apoptosis. Furthermore, quinoa and chia nanocapsule management repressed the activation of the MYC and PIK3CA genes. As well as nanocapsules modulated the liver enzymes and kidney function alterations induced in mammary tumor animals. Meanwhile, both oils' nanocapsules do not have an impact on the liver and kidneys of healthy rats.ConclusionsThe findings indicate that quinoa and chia nanocapsules are safe and can reduce tumor growth, suggesting a potential natural therapeutic target for breast cancer treatment.

The Dietary Fiber Inulin Slows Progression of Chronic Kidney Disease-Mineral Bone Disorder (CKD-MBD) in a Rat Model of CKD.

Chronic kidney disease (CKD)-mineral bone disorder (CKD-MBD) leads to fractures and cardiovascular disease. Observational studies suggest beneficial effects of dietary fiber on both bone and cardiovascular outcomes, but the effect of fiber on CKD-MBD is unknown. To determine the effect of fiber on CKD-MBD, we fed the Cy/+ rat with progressive CKD a casein-based diet of 0.7% phosphate with 10% inulin (fermentable fiber) or cellulose (non-fermentable fiber) from 22 weeks to either 30 or 32 weeks of age (~30% and ~15% of normal kidney function; CKD 4 and 5). We assessed CKD-MBD end points of biochemistry, bone quantity and quality, cardiovascular health, and cecal microbiota and serum gut-derived uremic toxins. Results were analyzed by two-way analysis of variance (ANOVA) to evaluate the main effects of CKD stage and inulin, and their interaction. The results showed that in CKD animals, inulin did not alter kidney function but reduced the increase from stage 4 to 5 in serum levels of phosphate and parathyroid hormone, but not fibroblast growth factor-23 (FGF23). Bone turnover and cortical bone parameters were similarly improved but mechanical properties were not altered. Inulin slowed progression of aorta and cardiac calcification, left ventricular mass index, and fibrosis. To understand the mechanism, we assessed intestinal microbiota and found changes in alpha and beta diversity and significant changes in several taxa with inulin, together with a reduction in circulating gut derived uremic toxins such as indoxyl sulfate and short-chain fatty acids. In conclusion, the addition of the fermentable fiber inulin to the diet of CKD rats led to a slowed progression of CKD-MBD without affecting kidney function, likely mediated by changes in the gut microbiota composition and lowered gut-derived uremic toxins. © 2023 The Authors. JBMR Plus published by Wiley Periodicals LLC. on behalf of American Society for Bone and Mineral Research.

POLYPHENOL-RICH LEAF EXTRACT OF Moringa oleifera Lam. ATTENUATES NEPHROTOXICITY AND OXIDATIVE STRESS IN CARBON TETRACHLORIDE (CCl )- 4 TREATED ALBINO RATS

This study evaluated the effect of polyphenol-rich leaf extract of Moringa oleifera (PRE-M. o) in carbon tetrachloride (CCl4)-induced nephrotoxic rats. Thirty-six (36) male albino rats were randomly divided into 6 groups. Groups one to six received 1mL/kg olive oil (normal group), 1mL/kg CCl4 (toxicity control group), N-acetyl cysteine with 1mL/kg CCl4, 50mg/kg PRE-M. o with 1mL/kg CCl4, 100mg/kg PRE-M. o with 1mL/kg CCl4 and 250mg/kg PRE-M. o with 1mL/kg CCl4. PRE-M o was administered orally, once daily for seven days while CCl4 prepared in olive oil was administered intraperitoneally on day seven. Twenty-four hours after, animals were sacrificed and Kidneys were dissected for histology, kidney homogenates were prepared and blood samples were collected for biochemical and antioxidant parameters. Effects were investigated using biochemical indices of renal function and oxidative stress. Total phenol, which was quantified in the extract and expressed as mgGAE/g increased with increasing concentrations of the extract. CCl4 caused a significant increase in serum creatinine, urea and uric acid concentrations as well as a significant decrease in total protein and albumin. Malondialdehyde increased while Glutathione (GSH) and superoxide dismutase (SOD) decreased significantly in the CCl4-treated rats. Histopathological study revealed altered glomerular and tubular architecture with noticeable interstitial haemorrhage and infiltration of inflammatory cells in kidney of rats exposed to CCL4. Treatment with PRE-M. o was able to significantly revert all altered parameters which showed that PRE-M. o can restore altered kidney function and ameliorate oxidative stress.

Investigating kidney function changes in young adults with COVID-19: Serum creatinine level, glomerular filtration rate, and biochemical profile analysis

The study’s objective was to comprehensively assess kidney function alterations in patients with COVID-19. The study was carried out in Moscow (Russia) in 2021. 100 patients of 19-30 years old (51 females and 49 males) took part in the survey. The study collected participant data on basal urine, serum creatinine, and estimated glomerular filtration rate from medical histories before COVID-19 infection. COVID-19 diagnosis (delta strain) was confirmed by polymerase chain reaction test. Serum creatinine was measured, considering age and race. Micro-albuminuria levels from daily urine samples were established. Laboratory blood tests included quantitative indices of blood-forming elements, hemoglobin levels, and biochemical parameters. Based on the results, the study observed a slight increase in serum creatinine levels after COVID-19 infection, with concentrations of 78.4±6.4 mmol/L before infection and 87.5±7.7 mmol/L after the disease (p≥0.05). The microalbuminuria-creatinine ratio also showed an increase. The glomerular filtration rate in renal glomeruli declined from 93.3±10.1 mL/min/1.73 m&lt;sup&gt;2&lt;/sup&gt; before infection to 78.9±8.7 mL/min/1.73 m&lt;sup&gt;2&lt;/sup&gt; after the disease (p≥0.05). These findings suggest a trend towards decreased kidney function in young patients with moderate COVID-19 severity. However, normoalbuminuric compared to creatinine was significantly higher than normal after COVID-19. Urine tests indicated a trend of decreased renal glomerular filtration rate. Clinical symptoms included high temperature, weakness, cough, and, in some cases, liquid stools. Laboratory findings revealed significant deviations in hematocrit, neutrophil, and eosinophil concentrations. Parallel tests focusing on cystatin C and beta-2 macroglobulin are recommended to assess kidney function and identify potential dysfunction.

The role of renal circadian biorhythms in lifelong LUTS.

This article delves into the intricate relationship between kidney function, diuresis, and lower urinary tract symptoms (LUTS) throughout the transitions of the human lifespan. It explores circadian regulation of urine production, maturation of renal function from birth to adulthood, and effects of aging on kidney function and LUTS. The complex connections between these factors are highlighted, offering insights into potential interventions and personalized management strategies. An international panel of seven experts engaged in online discussions, focusing on kidney function, diuresis, and LUTS throughout life. This manuscript summarizes expert insights, literature reviews, and findings presented during a webinar and subsequent discussions. Renal function undergoes significant maturation from birth to adulthood, with changes in glomerular filtration rate, diuresis, and tubular function. A circadian rhythm in urine production is established during childhood. Adolescents and young adults can experience persistent enuresis due to lifestyle factors, comorbidities, and complex physiological changes. In older adults, age-related alterations in kidney function disrupt the circadian rhythm of diuresis, contributing to nocturnal polyuria and LUTS. The interplay between kidney function, diuresis, and LUTS is crucial in understanding lifelong urinary health. Bridging the gap between pediatric and adult care is essential to address enuresis in adolescents and young adults effectively. For older adults, recognizing the impact of aging on renal function and fluid balance is vital in managing nocturia. This holistic approach provides a foundation for developing innovative interventions and personalized treatments to enhance quality of life for individuals with LUTS across all stages of life.

Role of Cardiac Troponins in Predicting Adverse Outcomes in Acute Coronary Syndrome With Renal Dysfunction.

A substantial global cause of mortality as well as disability is acute myocardial infarction (AMI). It is alsowidespread knowledge that patients with chronic kidney disease (CKD) possess greater mortality and cardiovascular disease risks than the rest of the population. A vital biomarker for the diagnosis of AMI is high-sensitive cardiac troponin T (hs-cTnT). Individuals afflicted with severe CKDfrequently exhibit increased hs-cTnTlevels, which can pose a significant diagnostic challenge in cases of non-ST elevation acute coronary syndrome (NSTE-ACS) necessitating revascularization. Alteration in kidney function exerts an impact on troponin levels, making a single value less useful. As the renal population has an increased risk of non-ST-segment elevation myocardial infarction (NSTEMI), serial tracking of cardiac biomarkers is essential to detect ACS in this population. Numerous studies using algorithmic remedies based on admission troponin and spontaneous variations in troponin concentration have been put forth by researchers to address these issues. A considerable majority of CKD patients can be accurately diagnosed or excluded from having AMI using the approach, which involves serial measures. Patients who suffer from kidney impairment exhibit lesser chances of undergoing angiography or revascularizationand receiving preventative therapies. Furthermore, their outcomes are comparatively poorer when compared to patients who possess normal kidney function. Despite studies indicating a higher risk of poor outcomes after AMI in this population, these patients are less likely to receive guideline-indicated care. In this study, we employed a systematic literature review (SLR) methodology to provide an account of the available studies and to draw attention to the importance of cardiac troponins in predicting unfavorable outcomes and algorithms in the prediction, diagnosis, and prognosis of patients with ACS and renal impairment. Eight papers were chosen for in-depth analysis after reviewing 86 articles from trusted publications between 2013 and August 3, 2023. The analysis considered factors such as sensitivity, severity of renal damage, algorithms used, the benefits of algorithms, and the challenges. One must examine the change in cardiac troponin (cTn) and take higher cut-off values into consideration in order to increase the sensitivity and specificity for the diagnosis of AMI. Higher levels of cTn have also been correlated prognostically to unfavorable outcomes like incident heart failure and death from cardiovascular causes. Also, raised troponin levels have been linked to all-cause and cardiovascular death in both dialysis patients and patients with CKD who did not receive dialysis. Future studies should concentrate on whether troponin testing can reclassify risk and provide treatment in people with CKD who are at the greatest threat of death. The clinical practice benefits of routinely measuring cardiac troponin concentrations are largely unknown. Future research should also concentrate on figuring out how troponin testing can influence clinical management and how to address the root reasons for chronic hs-cTnT elevation in patients with CKD, which may include elements like uremic toxicity, macrovascular or microvascular ischemia, anemia, as well as reduced renal clearance.