BACKGROUND: This observational cross-sectional study aimed to identify predictors of renal complications in pediatric patients with sickle cell disease (SCD) at King Salman Armed Forces Hospital, Tabuk, Saudi Arabia, over six months from February 2023 to July 2023. The study evaluated microalbuminuria as an early indicator of renal injury and explored its correlations with clinical and laboratory parameters and abdominal ultrasound (US) findings.
METHODS: Included were pediatric patients aged 1 to 14 years with confirmed SCD, excluding those with acute infections or pre-existing renal diseases. Data from 100 patients\' electronic medical records were analyzed using IBM SPSS Statistics for Windows, Version 26 (Released 2019; IBM Corp., Armonk, New York, United States), with a significance set at p ≤ 0.05.
RESULTS: The mean age was 7.6 ± 3.3 years, with 51 males and 49 females; 11 were diagnosed with Hb-S-beta thalassemia. Hydroxyurea (HU) compliance was high, with only four non-compliant patients, though all took folic acid. Among 42 tested for albuminuria, all had negative results (<30 mg/g creatinine). A significant association was found between SCD diagnosis and kidney, ureter, and bladder (KUB) US results (p=0.008), with abnormal KUB findings more prevalent in the Hb-S-beta thalassemia group. Patients with abnormal KUB results had significantly lower mean weight (p=0.024). Additionally, Hb-S-beta thalassemia patients had lower mean weight than hemoglobin SS (HGSS) patients (p=0.04). Though not statistically significant, Hb-S-beta thalassemia patients had higher mean systolic blood pressure (p=0.053).
CONCLUSIONS: Significant associations were identified between SCD diagnosis type and renal US results, with lower body weight emerging as a potential predictor of renal complications. High HU compliance and its impact on renal outcomes warrant further investigation. Routine monitoring of microalbuminuria and KUB US may aid early detection of renal complications in pediatric SCD patients. Further studies with larger sample sizes are recommended to validate these findings and develop comprehensive renal protective strategies.

UNASSIGNED: Mirabegron (MIRG) is a type of β3 adrenoceptor agonist that is considered an alternative therapy for the treatment of overactive bladder (OAB) symptoms. Cilostazol (CITZ) is a selective inhibitor of phosphodiesterase (III) that has various pharmacological effects.
UNASSIGNED: The current study aimed to highlight the regulatory effects of CITZ on MIRG-induced toxicity.
UNASSIGNED: Male rats were divided into six groups. Blood samples were collected to determine different hepatic and kidney function levels along with serum protein electrophoresis and inflammatory factor levels. Histopathological studies and oxidative stress (OS) were also assessed. Kidney and hepatic damage were detected following the administration of MIRG, especially at high doses, due to elevated OS, inflammation, and apoptotic marker levels.
UNASSIGNED: Rats receiving CITZ exhibited significant improvements in both hepatic and kidney functions, with decreased inflammation and OS.
UNASSIGNED: CITZ administration plays a beneficial role in alleviating hepatic and nephrotoxicity induced by MIRG by inhibiting OS and inflammation.

UNASSIGNED: Carotid-femoral pulse wave velocity (cfPWV) and ejection duration (ED) have different impacts on target organ damage (TOD). The aim of this study was to determine the relationship of cfPWV and ED with TOD.
UNASSIGNED: A total of 1254 patients (64.27% males) from Ruijin Hospital were enrolled in this study from December 2018 to August 2022. Medical records, blood samples and urine samples were collected. The cfPWV was measured and ED was generated using SphygmoCor software (version 8.0, AtCor Medical, Sydney, Australia). TOD including left ventricular hypertrophy (LVH), microalbuminuria, chronic kidney disease (CKD), and abnormality of carotid intima-media thickness (CIMT) were evaluated.
UNASSIGNED: Multiple stepwise linear regression models of cfPWV and ED (individually or together) showed that cfPWV was positively correlated with left ventricular mass index (LVMI) ( β = 0.131, p = 0.002) and Log (albumin-creatinine ratio, ACR) ( β = 0.123, p = 0.004), while ED was negatively correlated with LVMI ( β = -0.244, p < 0.001) and positively correlated with the estimated glomerular filtration rate (eGFR) ( β = 0.115, p = 0.003). When cfPWV and ED were added separately or together in multiple stepwise logistic regression models, cfPWV was associated with CKD [odds ratio (OR) = 1.240, 95% confidence interval (CI) 1.055-1.458, p = 0.009], while ED was associated with LVH (OR = 0.983, 95% CI 0.975-0.992, p < 0.001). In the control group with normal cfPWV and normal ED, LVH was significantly lower in patients with high ED (OR = 0.574, 95% CI 0.374-0.882, p = 0.011), but significantly elevated in those with high cfPWV and low ED (OR = 6.799, 95% CI 1.305-35.427, p = 0.023).
UNASSIGNED: cfPWV was more strongly associated with renal damage, while ED was more strongly associated with cardiac dysfunction. cfPWV and ED affect each other, and together have an effect on LVH.

Typical hemolytic uremic syndrome (HUS) can occur as a severe systemic complication of infections with Shiga toxin (Stx)-producing Escherichia coli. Its pathology can be induced by Stx types, resulting in toxin-mediated damage to renal barriers, inflammation, and the development of acute kidney injury (AKI). Two sphingosine kinase (SphK) isozymes, SphK1 and SphK2, have been shown to be involved in barrier maintenance and renal inflammatory diseases. Therefore, we sought to determine their role in the pathogenesis of HUS. Experimental HUS was induced by the repeated administration of Stx2 in wild-type (WT) and SphK1 (SphK1-/-) or SphK2 (SphK2-/-) null mutant mice. Disease severity was evaluated by assessing clinical symptoms, renal injury and dysfunction, inflammatory status and sphingolipid levels on day 5 of HUS development. Renal inflammation and injury were found to be attenuated in the SphK2-/- mice, but exacerbated in the SphK1-/- mice compared to the WT mice. The divergent outcome appeared to be associated with oppositely altered sphingolipid levels. This study represents the first description of the distinct roles of SphK1-/- and SphK2-/- in the pathogenesis of HUS. The identification of sphingolipid metabolism as a potential target for HUS therapy represents a significant advance in the field of HUS research.

UNASSIGNED: Acute liver and kidney injury is the most common complication after aortic surgery, which seriously affects the survival and safety of perioperative patients. The presence of chronic preoperative liver and renal insufficiency, presence of preoperative blood inflammation indicators, duration of intraoperative extracorporeal circulation, and volume of red blood cell transfusion are the main influencing factors for acute postoperative liver and kidney injuries. In recent years, with the research progress on oxidative stress, a growing body of evidence has demonstrated that oxidative stress may cause tissue damage after ischemia-reperfusion (IR). However, the impact of the oxidative stress of distal tissues caused by IR on liver and renal cells after arterial surgeries has not yet been elucidated.
UNASSIGNED: New Zealand white rabbits were used for the experiments and were divided into three groups. Among them, two groups were fed high-fat feed to establish a white rabbit model of hypertriglyceridemia, whereas the control group was provided with ordinary feed. In the experiment, white rabbits were subjected to occlusion of the infrarenal aorta abdominalis to simulate IR of the lower limbs. The effects of high triglyceride levels after the arterial IR of the lower limbs were investigated using the contents of reactive oxygen species (ROS) and malondialdehyde (MDA), a fat metabolite, in ischemic muscle tissues and blood tissues. One of the groups receiving high-fat feed received intervention with reduced glutathione (GSH) before IR of the lower limbs. Pathological studies were performed to identify the expression levels of inflammatory factors and inflammatory cells in liver and renal cells as well as cell apoptosis. The effects of GSH administration before IR on reducing the oxidative stress in adipose tissues and alleviating liver and kidney damage after stress response were investigated.
UNASSIGNED: After IR, the increases in ROS and MDA in ischemic muscle tissues and blood tissues were higher in white rabbits with high triglyceride levels than in those that only received ordinary feed or received intervention with GSH. In addition, for white rabbits with high triglyceride levels, the TNF-α expression levels in the liver increased after IR. Moreover, a considerable increase in the expression of TNF-α, IL-6, macrophages, and T lymphocytes were observed in renal cells. A large number of inflammatory cells and the formation of immune complexes were also noted in the glomeruli; in addition, cell apoptosis was promoted.
UNASSIGNED: This study showed that high triglyceride levels enhanced the oxidative stress response and increased ROS production in New Zealand white rabbits after arterial IR of the lower limbs. High ROS levels activated the expression of inflammatory factors and inflammatory cells in the liver and kidney, which affected cell functions and promoted apoptosis. At high triglyceride levels, GSH downregulated ROS production in oxidative stress after IR, thereby protecting liver and kidney functions.

UNASSIGNED: Hypoxia is one of the principal causes of renal diseases. This study aimed to evaluate the effects of Nigella sativa on dinitrophenol (DNP)-induced hypoxia renal damage in rats.
UNASSIGNED: Forty adult male rats were incorporated in this study. The rats were divided into four groups: control group, N. sativa group, DNP hypoxic group, and DNP + N. sativa group receiving N. sativa (400 mg/kg body weight). Serum and renal tissue erythropoietin (EPO) hormone and hypoxia-inducible factor-2α (HIF-2α) levels were measured. Renal oxidative stress biomarkers, inflammatory biomarkers, renal hemodynamics, and histopathological examination were evaluated.
UNASSIGNED: Administration of N. sativa highly significantly normalized serum EPO level, HIF-2α (P < 0.001 for each) in DNP + N. sativa treated rats as compared to DNP hypoxic rats. Furthermore, it highly significantly improved renal oxidative stress evident by decreased renal tissues malondialdehyde and increased superoxide dismutase, total thiol, and catalase activity (P < 0.001 for each). Furthermore, a highly significant decline of renal intercellular adhesion molecule-1, myeloperoxidase, and interleukin-6 was observed in DNP + N. sativa rats (P < 0.001 for each). Improvements in renal hemodynamics and kidney functions were also found after N. sativa administration (with P < 0.001 for all parameters). In addition, N. sativa treatment reduced renal histopathological changes of the DNP + N. sativa group. Our results were statistically analyzed using the Prism software package (GraphPad version 8.0).
UNASSIGNED: N. sativa has an alleviating effect on DNP-induced hypoxia renal damage and can restore kidney functions in rats\' animal models. These effects were through antioxidant, anti-inflammatory, and hemodynamic mechanisms.

OBJECTIVE: To evaluate the clinical features of patients with Systemic Lupus Erythematosus (SLE) and explore the risk factors of disease activity and renal damage.
METHODS: A retrospective study involving 194 patients were performed. Patients were divided into lupus nephritis (LN) group (63.40%) and non-LN group (36.60%), different disease activity group, and different renal function group according to the clinical data. Multivariate logistic regression analysis showed that albumin (ALB), uric acid (UC), total cholesterol (TC), and anti-dsDNA antibodies were the influencing factors of LN in patients with SLE (P < 0.05); ALB, UC, and complement 3(C3) were the influencing factors of lupus disease activity (P < 0.05); UC, C3, and hemoglobin (HB) were the influencing factors of abnormal renal function in SLE patients.
RESULTS: The results of the ROC curve showed that ALB, UA, and TC had certain predictive value for combined LN in patients with SLE, and the predictive value of ALB was greater than that of TC (P < 0.05); ALB, UA, and C3 being predictors of the activity of patients with SLE; BUN, UA, and HB all had certain predictive value for the abnormal renal function in patients with LN. SLE patients have the high incidence of renal impairment.
CONCLUSIONS: The results of this study suggest that patients with SLE should regularly monitor the levels of ALB, UA, TC, C3, and HB, as well as pay attention to the intervention of hyperlipidemia and hyperuricemia in patients with SLE to better control disease progression.

BACKGROUND: Complement activation may facilitate hypertension through its effects on immune responses. The anaphylatoxin C5a, a major inflammatory effector, binds to the C5a receptor 1 and 2 (C5aR1, C5aR2). We have recently shown that C5aR1-/- mice have reduced hypertensive renal injury. The role of C5aR2 in hypertension is unknown.
METHODS: For examination of C5aR2 expression on infiltrating and resident renal cells a tandem dye Tomato-C5aR2 knock-in reporter mouse was used. Human C5aR2 expression was analyzed in a single cell RNAseq data set from kidneys of hypertensive patients. Finally, we examined the effect of Ang II induced hypertension in C5aR2-deficient mice.
RESULTS: Flow cytometric analysis of leukocytes isolated from kidneys of the reporter mice showed that dendritic cells are the major C5aR2-expressing population (34%) followed by monocyte/macrophages (30%) and neutrophils (14%). Using confocal microscopy C5aR2 was not detected in resident renal or cardiac cells. In the human kidney C5aR2 was also mainly found in monocytes, macrophages and dendritic cells with a significantly higher expression in hypertension (p<0,05). Unilateral nephrectomy was performed followed by infusion of Ang II (0.75 ng/g/min) and a high salt diet in wildtype (n=18) and C5aR2-deficient mice (n=14). Blood pressure, renal injury (albuminuria, glomerular filtration rate, glomerular and tubulointerstitial injury, inflammation) and cardiac injury (cardiac fibrosis, heart weight, gene expression) did not differ between hypertensive wildtype and C5aR2-/- mice.
CONCLUSIONS: In summary, C5aR2 is mainly expressed on myeloid cells in the kidney in mice and humans but its deficiency has no effect in Ang II induced hypertensive injury.

BACKGROUND: Although renal damage is increasingly reported among the most undernourished patients with Anorexia Nervosa (AN), it remains underestimated in current practice, and often associated with acute dehydration. The purpose of our study was to evaluate the frequency, the extent, and the risk factors of renal involvement among adolescents and adults hospitalized in specialized units for AN.
METHODS: In this multi-center study, 197 consecutive participants were included, aged 13-65, from 11 inpatient eating disorder psychiatric units. Information on the course of AN, clinical characteristics, biological data, and medication were collected.
RESULTS: At admission, mean BMI was 13.1 (± 1.6) kg/m2 for a mean age of 20.74 (± 6.5) years and the z-score was - 3.6 (± 1.33). Six participants (3.0%) had hyponatremia, four (2.0%) had hypokalemia, and nine (4.5%) had hypochloremia. The Blood Urea Nitrogen/Creatinine ratio was over 20 for 21 (10.6%) participants. The mean plasma creatinine was 65.22 (± 12.8) µmol/L, and the mean eGFR was 74.74 (± 18.9) ml/min. Thirty- five participants (17.8%) had an eGFR > 90 ml/min, 123 (62.4%) from 60 to 90 ml/min, 35 (17.8%) from 45 to 60 ml/min, and 4 (2%) under 45 ml/min. In multivariate analysis, only BMI on admission was a determinant of renal impairment. The lower the BMI the more severe was the renal impairment.
CONCLUSIONS: When eGFR is calculated, it highlights renal dysfunction found in severe AN requiring hospitalisation in specialized units. The severity of undernutrition is an independent associated factor. Kidney functionality tests using eGFR, in addition to creatinine alone, should be part of routine care for patients with AN to detect underlying renal dysfunction.
AN is a psychiatric illness with organic repercussions that are not always visible nor frequently investigated. Renal damage, if detected, is often attributed to dehydration, and is thought to be rapidly reversible. Assessment of its severity and evolution is therefore not systematic, even in eating disorder units specialised in the care of patients with AN. Our study explored the assessment of renal impairment among adolescents and adults hospitalized in psychiatric units using eGFR calculation. Our results showed that fewer than 18% of the patients hospitalized had normal renal function and that among the various criteria, only BMI on admission was related to the extent of this impairment. Assessment of renal function by eGFR calculation and not only by creatinine measures should be performed routinely in all situations requiring hospitalization in anorexia nervosa, regardless of the reason for hospitalization.

BACKGROUND: Traditional biomarkers of chronic kidney disease (CKD) detect the disease in its late stages and hardly predict associated vascular damage. Integrin-linked kinase (ILK) is a scaffolding protein and a serine/threonine protein kinase that plays multiple roles in several pathophysiological processes during renal damage. However, the involvement of ILK as a biomarker of CKD and its associated vascular problems remains to be fully elucidated.
METHODS: CKD was induced by an adenine-rich diet for 6 weeks in mice. We used an inducible ILK knockdown mice (cKD-ILK) model to decrease ILK expression. ILK content in mice\'s peripheral blood mononuclear cells (PBMCs) was determined and correlated with renal function parameters and with the expression of ILK and fibrosis and inflammation markers in renal and aortic tissues. Also, the expression of five miRNAs that target ILK was analyzed in whole blood of mice.
RESULTS: The adenine diet increased ILK expression in PBMCs, renal cortex, and aortas, and creatinine and urea nitrogen concentrations in the plasma of WT mice, while these increases were not observed in cKD-ILK mice. Furthermore, ILK content in PBMCs directly correlated with renal function parameters and with the expression of renal and vascular ILK and fibrosis and inflammation markers. Finally, the expression of the five miRNAs increased in the whole blood of adenine-fed mice, although only four correlated with plasma urea nitrogen, and of those, three were downregulated in cKD-ILK mice.
CONCLUSIONS: ILK, in circulating mononuclear cells, could be a potential biomarker of CKD and CKD-associated renal and vascular damage.