Renal Abnormalities Research Articles

CD4+CD57+ senescent T cells as promoters of systemic lupus erythematosus pathogenesis and the therapeutic potential of senolytic BCL-2 inhibitor.

Systemic lupus erythematosus (SLE) is a complex autoimmune disease characterized by persistent activation of immune cells and overproduction of autoantibodies. The accumulation of senescent T and B cells has been observed in SLE and other immune-mediated diseases. However, the exact mechanistic pathways contributing to this process in SLE remain incompletely understood. In this study, we found that in SLE patients: (1) the frequency of CD4+CD57+ senescent T cells was significantly elevated and positively correlated with disease activity; (2) the expression levels of B-lymphoma-2 (BCL-2) family and interferon-induced genes (ISGs) were significantly upregulated; and (3) in vitro, the cytokine IL-15 stimulation increased the frequency of senescent CD4+ T cells and upregulated the expression of BCL-2 family and ISGs. Further, treatment with ABT-263 (a senolytic BCL-2 inhibitor) in MRL/lpr mice resulted in decreased: (1) frequency of CD4+CD44hiCD62L-PD-1+CD153+ senescent CD4+ T cells; (2) frequency of CD19+CD11c+T-bet+ age-related B cells; (3) level of serum antinuclear antibody; (4) proteinuria; (5) frequency of Tfh cells; and (6) renal histopathological abnormalities. Collectively, these results indicated a dominant role for CD4+CD57+ senescent CD4+ T cells in the pathogenesis of SLE and senolytic BCL-2 inhibitor ABT-263 may be the potential treatment in ameliorating lupus phenotypes.

Impact of inadequate empirical antibiotic treatment on outcome of non-critically ill children with bacterial infections

BackgroundThe impact of inadequate empirical antibiotic treatment on patient outcomes and hospitalization duration for non-life-threatening infections in children remains poorly understood. We aimed to assess the effects of inadequate empirical antibiotic treatment on these factors in pediatric patients.MethodsThe medical records of children admitted for infectious diseases with bacteria isolated from sterile sites between 2018 and 2020 were retrospectively reviewed. Patients who received adequate empirical treatment were compared with those who received inadequate treatment in terms of demographic, clinical, and laboratory variables.ResultsForty-eight patients who received inadequate empirical antimicrobial treatment were compared to 143 patients who received adequate empirical treatment. Inadequate empirical antimicrobial treatment did not significantly affect the length of hospital stay or the incidence of complications in non-critically ill children with bacterial infections. Younger age and underlying renal abnormalities were identified as risk factors for inadequate antimicrobial treatment, while associated bacteremia was more common in the adequate antimicrobial treatment group.Conclusionsinadequate antibiotic treatment did not affect the outcomes of non-critically ill children with bacterial infectious diseases. Therefore, routine empirical broad-spectrum treatment may not be necessary for these cases, as it can lead to additional costs and contribute to antibiotic resistance. Larger prospective studies are needed to confirm these findings.

New concepts in the physiopathology of hypertension. Purinergic receptors

Hypertension is a major risk of morbidity and mortality in patients when it is uncontrolled. In spite of improved therapies currently available for blood pressure control, their complications are far away from being accomplished. Therefore, chronic renal failure is frequently observed in hypertensive patients. Thus, insights on mechanisms that may contribute to arterial pressure control should be studied to prevent life-threatening cardiovascular disorders. Purinergic receptors have been recognized in the physiopathology of hypertension; this review summarizes their participation in the renal abnormalities of the kidney in hypertension. Several studies have suggested the activation of renal purinergic receptors under an elevated interstitial ATP milieu as a fundamental pathway that leads to generation and maintained hypertension. Elevated ATP concentration alters fundamental mechanisms involved in the long-term control of blood pressure such as pressure natriuresis, autoregulation of glomerular filtration rate and renal blood flow, as well as increased tubule-glomerular feedback responses, overall, these alterations decrease sodium excretion; in addition, the expression of ATP receptors is modified. Under a genetical background, ATP induces the production of vasoactive compounds, decreases renal function and induces tubulointerstitial injury before glomerular damage. Simultaneously, a deleterious interaction between angiotensin II and purinergic receptors lead to the progression of renal damage.

Urodynamic Abnormalities in Children with Primary Bilateral Vesicoureteral Reflux.

Bilateral vesicoureteral reflux (VUR) has been associated with poor long-term prognosis, and research focusing exclusively on its effect on urinary bladder function is lacking. This study aims to assess the urodynamic characteristics of children with bilateral VUR and identify factors influencing renal function. A retrospective analysis was performed on children diagnosed with bilateral VUR who underwent urodynamic examination in the outpatient department of our institution from January 2019 to January 2023. All patients underwent comprehensive assessments, including voiding cystourethrography, urinary system ultrasound and urodynamic examination, to analyse the urodynamic features associated with different clinical characteristics. The study included 148 children with bilateral VUR, amongst whom 92 (62.2%) exhibited urodynamic abnormalities, including idiopathic detrusor overactivity (DO) in 30 cases (20.3%) and dysfunctional voiding (DV) in 58 cases (39.2%). DV was prevalent in children under 5 years of age, whereas idiopathic DO was predominantly observed in children older than 2 years of age. Children older than 5 years of age exhibited a trend towards reduced bladder volume, whereas those younger than 2 years of age often had increased bladder volume and residual urine. Multivariate analysis identified bilateral severe VUR as an independent risk factor for abnormal estimated glomerular filtration rate. DV tends to be more common in younger children with larger bladder volumes and increased residual urine than in older children. By contrast, older children are more susceptible to idiopathic DO associated with smaller bladder volumes than younger children. Bilateral severe reflux increases the likelihood of renal functional abnormalities, which appear to be a consequence of congenital scarring rather than abnormalities in bladder function.

Cartilage within lipomyelomeningocele and ulnar longitudinal deficiency syndrome as VACTERL association, alliance in SHH/GLI3, and Wnt pathway: illustrative case.

Lipomyelomeningocele associated with an ulnar club hand in the spectrum of VACTERL association ([costo-]vertebral abnormalities; anal atresia; cardiac defects; tracheal-esophageal abnomalities, including atresia, stenosis, and fistula; renal and radial abnormalities; limb abnormalities; single umbilical artery) is a very rare and infrequently reported phenomenon. Within the fat mass of the lipoma, it is not common to find a well-defined cartilaginous mass with no attachments to the surrounding tissue. The authors present the case of a 3-month-old male with low-back swelling that was off-center to the left, accompanied by a left short forearm displaying outward bowing. Echocardiography showed an atrial septal defect. This rare VACTERL association comprises lipomyelomeningocele, atrial septal defect, and ulnar longitudinal deficiency syndrome. During surgical intervention for the lipoma, a well-defined cartilaginous mass was discovered within the adipose tissue. The manifestation of VACTERL association can be partially explained by the Shh/Gli and Wnt pathway defects. It is prudent to screen children with neural tube defects to be aware of any associated syndromes. This case is very rare, and the literature has contained no prior report on the VACTERL association of lipomyelomeningocele, atrial septal defect, and ulnar longitudinal deficiency.

Multiparametric renal function assessment in cirrhotic patients shows high prevalence of medically actionable changes in multiple modules.

Renal dysfunction is a common complication of cirrhosis, occurring either as part of multiorgan involvement in acute illness or secondary to advanced liver disease. To date, no study has comprehensively assessed multiple renal function parameters in hospitalized patients with cirrhosis through a multiparametric analysis of renal biochemistry markers. We conducted a retrospective, observational study including all consecutive patients hospitalized with cirrhosis who underwent a 43-multiparametric renal function assessment between January 1, 2021, and June 30, 2023. All patients showed at least one of the following renal abnormalities: Kidney Disease: Improving Global Outcomes stage G2 or higher, sodium and/or chloride excretion fraction <1%, electrolyte-free water clearance <0.4mL/min, or tubular maximum phosphate reabsorption capacity <0.8mmol/L. The estimated glomerular filtration rate equations significantly overestimated the measured creatinine clearance with median differences of +14mL/min/1.73m2 (95% CI 6-29) and +9mL/min/1.73m2 (95% CI 2-15) for European Kidney Function Consortium equations, respectively. Notably, 54% and 39% of patients demonstrated estimated glomerular filtration rates exceeding 30% of the measured creatinine clearance when the Chronic Kidney Disease - Epidemiology Collaboration and European Kidney Function Consortium formulas were employed, respectively. Substantial discrepancies in Kidney Disease: Improving Global Outcomes stage assignments were observed between the estimated glomerular filtration rate- and measured creatinine clearance-based assessments. This study underscores the value of a multiparametric renal function assessment as a routine tool for evaluating renal function in patients with cirrhosis. A high prevalence of medically actionable renal abnormalities spanning multiple renal function modules, including alterations in glomerular function, salt and solute-free water excretion, and proximal tubule phosphate reabsorption, has been demonstrated in hospitalized patients with cirrhosis.

Prevalence of Urinary Tract Infections and Antibiogram of Bacteria Isolated From Children With Sickle Cell Disease in Tanzania.

Introduction Individuals with sickle cell disease (SCD) are particularly vulnerable to urinary tract infections (UTIs) due to immunological deficits and renal abnormalities associated with the disorder. These infections can exacerbate underlying health issues and lead to severe complications if not managed promptly and effectively. Due to the heightened risk and potential consequences of UTIs in this population, this study aimed to determine their prevalence and explore the resistance patterns of causative pathogens among children attending the SCD Clinic at Muhimbili National Hospital (MNH), Dar es Salaam, Tanzania. Focusing on this demographic group, we sought to provide targeted insights to inform better clinical protocols and intervention strategies in regions heavily affected by SCD. Materials and methods This prospective cross-sectional study was conducted at the MNH, Dar es Salaam, Tanzania, with an enrollment over two months from 19th March to 21st May 2015. We diagnosed UTIs in children with SCD using dipstick and culture methods. Antibiotic susceptibility was assessed using the Kirby-Bauer disc diffusion method, evaluating resistance patterns to antibiotics such as ampicillin, cloxacillin, erythromycin, chloramphenicol, ceftriaxone, and trimethoprim-sulfamethoxazole. The diagnostic accuracy of the dipstick and culture methods was validated to ensure reliability in detecting UTIs. Statistical analysis was conducted using Statistical Product and Service Solutions (SPSS) software (Released 2019; IBM Corp., Armonk, New York, United States). Results Among the 250 children, 56 (22.4%) were UTI-positive according to the culture method and 62 (24.8%) were UTI-positive according to the dipstick test. Girls were more likely to be UTI-positive than boys (29.1% and 13.6%, respectively; p-value = 0.011). Escherichia coli was the most common uropathogen, followed by Klebsiella, Staphylococcus, Proteus, and Pseudomonas (44.2%, 26.9%, 21.2%, 3.8%, and 1.9%, respectively). All isolates were resistant to ampiclox. Resistance rates to ampicillin, erythromycin, cotrimoxazole, chloramphenicol, and ceftriaxone were 94.2%, 76.9%, 59.6%, 46.2%, and 21.2%, respectively. Conclusion This study indicated that dipsticks diagnosed more UTIs. The prevalence was higher in girls than in boys. Escherichia coli was the most commonly isolated antibiotic-resistant organism. High resistance levels were observed against the combination of ampicillin and cloxacillin. However,the isolates were less resistant to ceftriaxone. These results call for increased surveillance of resistant uropathogens in the pediatric population with SCD.

Are Kidneys Affected by SARS-CoV-2 Infection? An Updated Review on COVID-19-Associated AKI.

Human kidneys are an important target of SARS-CoV-2 infection, and many renal abnormalities have been found in patients with SARS-CoV-2 infection, including proteinuria, hematuria, and acute kidney injury. Acute kidney injury is now considered a common complication of COVID-19, and the epidemiology of AKI in SARS-CoV-2-infected patients continues to be controversial. We have carried out a narrative review to evaluate the frequency and risk factors for AKI among patients hospitalized due to COVID-19, and the latest surveys on this topic have been included. The mechanisms by which AKI occurs in COVID-19 patients have also been reviewed. Multiple risk factors for the development of AKI in patients with SARS-CoV-2 infection have been identified; these have been classified in various groups (management and background factors, among others). SARS-CoV-2 targets the kidneys by indirect activity, but SARS-CoV-2 infects tubular epithelial cells and podocytes. We retrieved 24 reports (n = 502,593 unique patients with SARS-CoV-2 infection) and found an incidence of AKI of 31.8% (range, 0.5% to 56.9%). Only a minority (n = 2) of studies had a prospective design. We found that the AKI risk was greater in SARS-CoV-2 patients who underwent in-hospital deaths vs. those who survived; the summary estimate of the unadjusted RR of AKI was 2.63 (95% CI, 2.37; 2.93) (random-effects model). A stratified analysis showed that the incidence of AKI was greater in those reports where the frequency of COVID-19-positive patients having comorbidities (diabetes mellitus, arterial hypertension, and advanced age) was high. The unadjusted relative risk (aRR) of AKI was greater in SARS-CoV-2 patients who underwent ICU admission vs. those who did not; the pooled estimate of AKI risk was 2.64 (95% CI, 1.96; 3.56) according to the random-effects model. AKI is a common complication of hospitalized SARS-CoV-2-infected patients, and some comorbidities are important risk factors for it. The direct activity of the virus on the kidneys has been mentioned in the pathogenesis of AKI in SARS-CoV-2 patients. Further studies are ongoing in order to identify the mechanisms underlying the kidney injury in this population. The role of AKI on survival in SARS-CoV-2-infected patients is another area of active investigation.

Olezarsen for Hypertriglyceridemia in Patients at High Cardiovascular Risk.

Reducing the levels of triglycerides and triglyceride-rich lipoproteins remains an unmet clinical need. Olezarsen is an antisense oligonucleotide targeting messenger RNA for apolipoprotein C-III (APOC3), a genetically validated target for triglyceride lowering. In this phase 2b, randomized, controlled trial, we assigned adults either with moderate hypertriglyceridemia (triglyceride level, 150 to 499 mg per deciliter) and elevated cardiovascular risk or with severe hypertriglyceridemia (triglyceride level, ≥500 mg per deciliter) in a 1:1 ratio to either a 50-mg or 80-mg cohort. Patients were then assigned in a 3:1 ratio to receive monthly subcutaneous olezarsen or matching placebo within each cohort. The primary outcome was the percent change in the triglyceride level from baseline to 6 months, reported as the difference between each olezarsen group and placebo. Key secondary outcomes were changes in levels of APOC3, apolipoprotein B, non-high-density lipoprotein (HDL) cholesterol, and low-density lipoprotein (LDL) cholesterol. A total of 154 patients underwent randomization at 24 sites in North America. The median age of the patients was 62 years, and the median triglyceride level was 241.5 mg per deciliter. The 50-mg and 80-mg doses of olezarsen reduced triglyceride levels by 49.3 percentage points and 53.1 percentage points, respectively, as compared with placebo (P<0.001 for both comparisons). As compared with placebo, each dose of olezarsen also significantly reduced the levels of APOC3, apolipoprotein B, and non-HDL cholesterol, with no significant change in the LDL cholesterol level. The risks of adverse events and serious adverse events were similar in the three groups. Clinically meaningful hepatic, renal, or platelet abnormalities were uncommon, with similar risks in the three groups. In patients with predominantly moderate hypertriglyceridemia at elevated cardiovascular risk, olezarsen significantly reduced levels of triglycerides, apolipoprotein B, and non-HDL cholesterol, with no major safety concerns identified. (Funded by Ionis Pharmaceuticals; Bridge-TIMI 73a ClinicalTrials.gov number, NCT05355402.).

First case of Hajdu-Cheney syndrome in Lithuania caused by novel NOTCH2 gene likely pathogenic variant

Hajdu-Cheney syndrome (HCS) is an extremely rare autosomal dominant skeletal disorder. The prevalence rate of less than 1 case per 1,000,000 newborns and only 50 cases were reported in the medical literature. HCS is characterized by progressive bone resorption in the distal phalanges (acro-osteolysis), progressive osteoporosis, distinct craniofacial changes, dental anomalies, and occasional association with renal abnormalities. HCS is caused by pathogenic variants in the NOTCH2 gene, 34th exon. We report first familial case of HCS caused by likely pathogenic variant of NOTCH2 gene c.6449delC, p.(Pro2150LeufsTer5).

Correlation Diagnostic Contribution of SPECT/CT Imaging to 99mTc-DTPA Dynamic Scintigraphy in Patients with Different Renal Pathologies

Introduction: Dynamic renal scintigraphy with 99mTechnetium diethylenetriaminepentaacetic acid (99mTc-DTPA) is a widely performed imaging method to evaluate kidney function of patients with various renal pathologies. However the one-stop-shop combination with subsequent SPECT/CT imaging is a rarely discussed topic. Objective: The aim of the study was to evaluate the diagnostic benefits of SPECT/CT imaging to 99mTc-DTPA dynamic renal scintigraphy. Materials and Methods: A group of 32 patients (21 females and 11 males) who underwent dy- namic nephroscintigraphy with subsequent SPECT/CT was retrospectively studied. A dose of 185MBq (5mCi) 99mTc-DTPA was intravenously applied. A low-dose non-contrast CT protocol was used for attenuation correction and anatomical correlation. Results: Impaired relative renal function in various degrees of left kidney was detected in 18 patients (56%) and of right kidney in 14 patients (44%). SPECT/CT imaging identified the particular cause for the renal dysfunction in the analyzed subjects. The hybrid imaging demonstrated urolithiasis in 11 patients, postoperative ureteral strictures in 5 patients, diagnosed urological cancer in 4 patients and external compression of ureter in 2 patients as a possible obstructive cause. Congenital renal anomalies were the identified causes of impaired renal function in 10 patients – hypoplastic kidney in 4 patients, duplex kidney in 2 patients, multiple cortical cysts in 2 patients, aberrant vessel obstructing the pyeloureteral segment in 1 patient and horseshoe kidney in 1 patient. Conclusion: Dynamic renal scintigraphy combined with SPECT/CT is a very useful clinical tool, by providing not only functional but also anatomical information of the urinary tract, especially in the evaluation of obstructive uropathies and congenital renal abnormalities, that has the potential to change clinical management.

AUTOTRANSPLANTATION WITH EXTRACORPORAL RECONSTRUCTION OF RENAL VESSELS: A CLINICAL CASE OF “THE NUTCRACKER SYNDROME” AND LEFT RENAL ARTERIES HYPOPLASIA COMBINATION

Ex vivo kidney autotransplantation with renal artery reconstruction is an effective method of surgical correction of vascular abnormalities (fibromuscular dysplasia, hypoplasia, and renal artery aneurysms) showing good long-term results. The combination of renal artery abnormalities with aorto-mesenteric compression syndrome (“the nutcracker” syndrome) is extremely rare and complicates the diagnosis making greatly. Renal artery hypoplasia is an abnormality that is rarely diagnosed and may not manifest clinically in the absence of contralateral kidney pathology as well as its vascular structures. Renal hypoplasia may be caused by mutations in the kidney development genes (HNF1B, PAX2, PBX1) and/or several environmental factors such as intrauterine growth retardation, maternal diseases (diabetes, hypertension), medication taken by the mother (renin-angiotensin system inhibitors or nonsteroidal anti-inflammatory drugs) and intoxication (smoking and alcohol). Premature delivery (before the 36th week) is also a risk factor due to incomplete nephrogenesis. Renal arteries hypoplasia is associated with fibromuscular dysplasia in most cases. The disease is characterized by non-inflammatory non-uniform focal hyperplasia of the renal artery wall with damage to small and medium arteries. Simultaneous damage to two or more vascular segments is detected in 25% of patients.&#x0D; A clinical case of successful treatment of “the nutcracker” syndrome (annular renal vein) combined with hypoplasia of the left main and accessory renal arteries associated with fibromuscular dysplasia is described. A 27-year-old female was admitted to the Department of Vascular Surgery of Municipal Noncommercial Enterprise of the Lviv Regional Council “Lviv Regional Clinical Hospital” on October 4, 2021, with complaints of pain in the left lumbar region and the left half of the abdomen, hematuria, proteinuria, a persistent increase in blood pressure. Ultrasound of the renal veins: the left renal vein in the aorto-mesenteric segment was not visualized, the posterior portion of the left renal vein was determined. Peak systolic velocity was up to 230 cm/s at the point of confluence with the inferior vena cava and 28 cm/s more distally. The vein was up to 12.0 mm in the renal hilum and up to 11.0 mm in the middle third. MSCT of the abdominal cavity, retroperitoneal space and pelvic organs: CT signs of pyelonephritis of the left kidney. Hypoplasia of the left kidney. Reactive para-aortic lymphadenopathy on the left. Hypoplastic left renal artery (3,8 mm) and presense of accessory ones, annular left renal vein. Angiomyolipoma of the right kidney (2,6 cm). Varicose veins of the small pelvis on the left. The patient underwent surgical treatment, namely ex vivo autovenous prosthetic repair of the left renal artery with autotransplantation of the left kidney. The course of the postoperative period was without complications, the reconstruction was functioning. Ultrasound of the renal vessels (1 week after the surgery): the blood flow was located in the renal hilum in the course of Doppler sonography of intrarenal branches. Venous outflow was unobstructed. Corticomedullary differentiation was marked satisfactorily.&#x0D; The study presented by us demonstrates the effectiveness of kidney autotransplantation for the correction of renal vascular abnormalities.&#x0D; Though of a solitary nature, the combination of renal vessels abnormalities complicates significantly the course of the disease and the possibilities of this pathology diagnostics.

Astragaloside IV attenuates renal tubule injury in DKD rats via suppression of CD36-mediated NLRP3 inflammasome activation.

In recent years, diabetic kidney disease (DKD) has emerged as a prominent factor contributing to end-stage renal disease. Tubulointerstitial inflammation and lipid accumulation have been identified as key factors in the development of DKD. Earlier research indicated that Astragaloside IV (AS-IV) reduces inflammation and oxidative stress, controls lipid accumulation, and provides protection to the kidneys. Nevertheless, the mechanisms responsible for its protective effects against DKD have not yet been completely elucidated. The primary objective of this research was to examine the protective properties of AS-IV against DKD and investigate the underlying mechanism, which involves CD36, reactive oxygen species (ROS), NLR family pyrin domain containing 3 (NLRP3), and interleukin-1β (IL-1β). The DKD rat model was created by administering streptozotocin along with a high-fat diet. Subsequently, the DKD rats and palmitic acid (PA)-induced HK-2 cells were treated with AS-IV. Atorvastatin was used as the positive control. To assess the therapeutic effects of AS-IV on DKD, various tests including blood sugar levels, the lipid profile, renal function, and histopathological examinations were conducted. The levels of CD36, ROS, NLRP3, Caspase-1, and IL-1β were detected using western blot analysis, PCR, and flow cytometry. Furthermore, adenovirus-mediated CD36 overexpression was applied to explore the underlying mechanisms through in vitro experiments. In vivo experiments demonstrated that AS-IV significantly reduced hyperglycemia, dyslipidemia, urinary albumin excretion, and serum creatinine levels in DKD rats. Additionally, it improved renal structural abnormalities and suppressed the expression of CD36, NLRP3, IL-1β, TNF-α, and MCP-1. In vitro experiments showed that AS-IV decreased CD36 expression, lipid accumulation, and lipid ROS production while inhibiting NLRP3 activation and IL-1β secretion in PA-induced HK-2 cells. AS-IV alleviated renal tubule interstitial inflammation and tubule epithelial cell apoptosis in DKD rats by inhibiting CD36-mediated lipid accumulation and NLRP3 inflammasome activation.

Renoprotective effect of hyperin against CdCl2 prompted renal damage by activation of Nrf-2/Keap-1 ARE pathway in male mice

Objectives This study explored the mitigating properties of hyperin (HYP) on renotoxicity induced by cadmium chloride (CdCl2). Methods Four groups of seven male albino mice each were used in this experiment. Group 1 served as the control, receiving no treatment. Group 2 received daily oral gavage of CdCl2 at 0.3 mg/kg body weight for 28 d. Group 3 received both CdCl2 (0.3 mg/kg) and HYP (100 mg/kg) daily using the same administration method. Finally, Group 4 received only HYP (100 mg/kg) daily. Results Cd exposure significantly increased kidney dysfunction markers (blood urea nitrogen and creatinine) and oxidative stress (reactive oxygen species [ROS] and malondialdehyde [MDA]). Conversely, it decreased antioxidant enzyme activities (glutathione peroxidase (GPx] and catalase [CAT]) and glutathione (GSH) levels. Nuclear factor erythroid 2-related factor 2 (Nrf-2) and antioxidant gene expression decreased, while Kelch-like ECH-associated protein 1 expression increased. Additionally, Cd exposure increased inflammatory mediators (nuclear factor kappa B, tumor necrosis factor alpha [TNF-α], interleukin-1β [IL-1β], and cyclooxygenase-2) and apoptotic markers (Bax and caspase-3), alongside decreased Bcl-2 expression and renal tissue abnormalities. Mitochondrial dysfunction manifested with diminished activities of Krebs cycle and respiratory chain enzymes, and reduced mitochondrial membrane potential. Co-treatment with HYP significantly attenuated these detrimental effects through its anti-apoptotic, antioxidant, and anti-inflammatory properties. Conclusion HYP co-treatment significantly attenuated CdCl2-induced renal damage in mice, suggesting its potential as a protective agent against Cd-induced kidney toxicity.

Clinical features and management of women with Mayer-Rokitansky-Küster-Hauser syndrome in a Thai population.

This study aimed to describe the clinical features, associated extragenital anomalies, and management of Mayer- Rokitansky-Küster-Hauser (MRKH) syndrome in a Thai population. This retrospective study analyzed the medical records of 96 patients with MRKH syndrome diagnosed and treated at a university hospital and tertiary referral center in southern Thailand between 2000 and 2022. The study included 96 patients with MRKH syndrome. The most common symptom was primary amenorrhea (88.5%), followed by difficulty or inability to engage in sexual intercourse (9.4%) and pelvic mass (2.1%). Notably, 80.3% of the patients did not have extragenital malformations and were diagnosed with MRKH type I (typical form), whereas 19.7% were categorized as MRKH type II (atypical form). Skeletal malformations were the most frequent extragenital anomalies and were present in 19.5% of patients, with scoliosis being the most common skeletal condition. Other extragenital malformations included renal (8.5%) and neurological (1.0%) abnormalities. Clinical vaginal examination revealed complete atresia in 21.8% and vaginal hypoplasia (median vaginal length, 3 cm) in 78.2% of the patients. Half of the patients did not receive treatment because they had not engaged in sexual intercourse. In this cohort, 41.7% of the patients had no difficulty performing sexual intercourse. Hence, self-dilation therapy or concomitant dilation was recommended. Only eight patients (8.3%) underwent surgical reconstruction of the vagina. This study confirmed the complexity and heterogeneity of the phenotypic manifestations of MRKH, including the degree of vaginal atresia and types and rates of associated malformations.

A Comparison of 68Ga-PSMA PET/CT-Based Split Renal Function with 99mTc-MAG3 Renography in Patients with Metastatic Castration-Resistant Prostate Carcinoma Treated with 177Lu-PSMA.

Physiological PSMA expression in the cells of the proximal renal tubules and consecutive radiopharmaceutical binding and retention could potentially lead to radioligand-therapy-induced nephrotoxicity. Thus, patients with metastatic castration-resistant prostate cancer undergo 99mTc-Mercaptoacetyltriglycine (MAG3) renal scintigraphy to assess kidney function and to exclude renal obstruction as part of their workup for PSMA-targeted radioligand therapy (RLT). 99mTc-MAG-3 renal scintigraphy often requires an additional visit to the nuclear medicine department and patients spend 30-90 min in the department, which is inconvenient and takes up camera time. In addition, the patients are subjected to a baseline 68Ga-PSMA PET/CT to assess for PSMA-positive disease prior to targeted radioligand therapy. The aim of this retrospective cross-sectional study was to compare 99mTc-MAG-3-based split renal function (SRF) with 68Ga-PSMA-derived SRF. This retrospective cross-sectional study included 28 patients with histologically proven metastatic castration-resistant prostate cancer (mCRPC) who received 177Lu-PSMA617. A comparison between the split renal function using 68Ga-PSMA PET/CT and the 99mTc-MAG-3-derived split renal function was carried out in 56 kidneys (n = 56). The SRF on 68Ga-PSMA was calculated using the volume and the average standard uptake value (SUVmean) within each VOI calculated as previously described by Roser et al.: SRF = (VOLUMEright) ∗ SUVmeanright/(VOLUMEright ∗ SUVmeanright + VOLUMEleft ∗ SUVmeanleft). Paired tests and correlation coefficients were used to compare 68Ga-PSMA and 99mTc-MAG-3. A visual comparison of kidney morphology on both studies was also performed. The median SRF of the right kidney was 49.9% (range: 3-91%) using 68Ga-PSMA PET/CT and 50.5% (range: 0-94%) with 99mTc-MAG3 scintigraphy. Notably, there was a strong correlation between SRF measurements obtained from PSMA and 99mTcMAG3, with a Pearson correlation coefficient of 0.957 (p < 0.001). Both 99mTc-MAG3 and 68Ga-PSMA PET/CT studies identified morphological renal abnormalities; there were nine hydronephrotic kidneys, four shrunken kidneys and one obstructed kidney, and there was a strong positive correlation between 68Ga-PSMA kidney morphology and 99mTcMAG3 renal scintigraphy kidney morphology, with a correlation coefficient of 0.93. PSMA-derived split function demonstrated a high correlation with renal function assessed on diuretic 99mTc-MAG3 renograms. PET-derived split renal function may, therefore, be considered an alternative to diuretic renogram-based split function. Furthermore, both 99mTc-MAG3 and 68Ga-PSMA PET/CT studies identified morphological renal abnormalities such as hydronephrosis, shrunken and obstructed kidneys. This correlation underscores the potential utility of 68Ga-PSMA imaging as a valuable tool for assessing kidney morphology as an alternative to renogram split function in clinical practice.

Amelioration of diabetic nephropathy in mice by a single intravenous injection of human mesenchymal stromal cells at early and later disease stages is associated with restoration of autophagy

Background and aimsMesenchymal stromal cells (MSCs) a potentially effective disease-modulating therapy for diabetic nephropathy (DN) but their clinical translation has been hampered by incomplete understanding of the optimal timing of administration and in vivo mechanisms of action. This study aimed to elucidate the reno-protective potency and associated mechanisms of single intravenous injections of human umbilical cord-derived MSCs (hUC-MSCs) following shorter and longer durations of diabetes.MethodsA streptozotocin (STZ)-induced model of diabetes and DN was established in C57BL/6 mice. In groups of diabetic animals, human (h)UC-MSCs or vehicle were injected intravenously at 8 or 16 weeks after STZ along with vehicle-injected non-diabetic animals. Diabetes-related kidney abnormalities was analyzed 2 weeks later by urine and serum biochemical assays, histology, transmission electron microscopy and immunohistochemistry. Serum concentrations of pro-inflammatory and pro-fibrotic cytokines were quantified by ELISA. The expression of autophagy-related proteins within the renal cortices was investigated by immunoblotting. Bio-distribution of hUC-MSCs in kidney and other organs was evaluated in diabetic mice by injection of fluorescent-labelled cells.ResultsCompared to non-diabetic controls, diabetic mice had increases in urine albumin creatinine ratio (uACR), mesangial matrix deposition, podocyte foot process effacement, glomerular basement membrane thickening and interstitial fibrosis as well as reduced podocyte numbers at both 10 and 18 weeks after STZ. Early (8 weeks) hUC-MSC injection was associated with reduced uACR and improvements in multiple glomerular and renal interstitial abnormalities as well as reduced serum IL-6, TNF-α, and TGF-β1 compared to vehicle-injected animals. Later (16 weeks) hUC-MSC injection also resulted in reduction of diabetes-associated renal abnormalities and serum TGF-β1 but not of serum IL-6 and TNF-α. At both time-points, the kidneys of vehicle-injected diabetic mice had higher ratio of p-mTOR to mTOR, increased abundance of p62, lower abundance of ULK1 and Atg12, and reduced ratio of LC3B to LC3A compared to non-diabetic animals, consistent with diabetes-associated suppression of autophagy. These changes were largely reversed in the kidneys of hUC-MSC-injected mice. In contrast, neither early nor later hUC-MSC injection had effects on blood glucose and body weight of diabetic animals. Small numbers of CM-Dil-labeled hUC-MSCs remained detectable in kidneys, lungs and liver of diabetic mice at 14 days after intravenous injection.ConclusionsSingle intravenous injections of hUC-MSCs ameliorated glomerular abnormalities and interstitial fibrosis in a mouse model of STZ-induced diabetes without affecting hyperglycemia, whether administered at relatively short or longer duration of diabetes. At both time-points, the reno-protective effects of hUC-MSCs were associated with reduced circulating TGF-β1 and restoration of intra-renal autophagy.Graphical abstract

Adult patients treated for bladder exstrophy at a young age: What are their current demands?

Bladder exstrophy-epispadias complex is a rare condition that necessitates numerous surgical procedures during a patient's youth to achieve adequate urine storage and continence. This study aimed to identify the specific needs and functional challenges faced by adults who underwent pediatric bladder exstrophy reconstructions and assessing the management of these issues in an adult population. A retrospective chart review was conducted for all bladder exstrophy complex patients who underwent surgery at a young age and were subsequently referred to our center between 2005 and 2020. Inclusion criteria included patients with cloacal or classical bladder exstrophy older than 18 years. We recorded the reasons for referral, management of contemporary complaints, types of past and present urinary reconstructions, and their current functional status. The study included 38 patients. The primary reasons for referral were incontinence (39%) and catheterization difficulties (24%). Management typically involved partial or complete surgical revision of their urinary reservoir, occasionally combined with a bladder neck procedure. Ultimately, only three patients continued to experience incontinence, while none reported catheterization issues after they underwent treatment at our center. Long-term exstrophy-related reconstruction complications included urinary tract infections (39%), stones (29%), stenosis (24%), fistulas (13%), chronic renal disease (16%), metabolic abnormalities (3%), and cancer (3%). Adults who previously underwent bladder exstrophy reconstruction exhibit a wide range of urologic reconstructions. Their needs often revolve around continence and catheterization concerns. Most patients with satisfactory functional outcomes perform selfcatheterization through a continent cutaneous channel and have either a continent pouch or an augmented bladder.

Renal sinus fat is associated with intrarenal hemodynamic abnormalities independent of visceral fat in patients with chronic kidney disease

ObjectiveObesity is a risk factor of chronic kidney disease (CKD), contributing to the rising incidence of cardiometabolic diseases. Renal sinus fat (RSF) is an ectopic fat depot located at the renal cavity that could impair renal function and hemodynamic through compression of renal structures. The major purpose of this study was to explore the relationship between RSF accumulation and renal dysfunction in CKD patients. MethodsWe evaluated the associations between computed tomography measured RSF volume and key clinical and histologic parameters involved in renal function and hemodynamics in 132 well-characterized CKD patients who underwent renal biopsy (median age: 62 years; 63.6% men). ResultsRSF volume normalized by renal volume (RSF%) positively correlated with obesity-related traits such body mass index and visceral fat volume (VFV) (all P < 0.001) whereas it negatively correlated with estimated glomerular filtration rate (eGFR) (ρ = −0.42, P < 0.001) and 24-h urinary creatinine clearance (CCr) (ρ = −0.34, P < 0.001). Notably, we found robust positive correlations between RSF% and renal resistive index (RRI) measured by the Doppler ultrasound (ρ = 0.40, P < 0.001), and the histological severity of global glomerular sclerosis (ρ = 0.48, P < 0.001) and interstitial fibrosis and tubular atrophy (IFTA) (ρ = 0.35, P < 0.001). In the multivariate linear regression models, after accounting for potential confounders including VFV, RSF% remained significantly associated with CCr (β = −0.26, P < 0.001), RRI (β = 0.17, P = 0.022), global glomerular sclerosis (β = 0.21, P = 0.002), and IFTA (β = 0.17, P = 0.012). ConclusionRSF accumulation is associated with renal dysfunction and hemodynamic abnormalities independent of visceral adiposity. Our results suggest that RSF may have a potential unique role in the pathogenesis of CKD.

Structural effect of the H992D/H418D mutation of angiotensin-converting enzyme in the Indian population: implications for health and disease

The Non synonymous SNPs (nsSNPs) of the renin-angiotensin-system (RAS) pathway, unique to the Indian population were investigated in view of its importance as an endocrine system. nsSNPs of the RAS pathway genes were mined from the IndiGenome database. Damaging nsSNPs were predicted using SIFT, PredictSNP, SNP and GO, Snap2 and Protein Variation Effect Analyzer. Loss of function was predicted based on protein stability change using I mutant, PremPS and CONSURF. The structural impact of the nsSNPs was predicted using HOPE and Missense3d followed by modeling, refinement, and energy minimization. Molecular Dynamics studies were carried out using Gromacsv2021.1. 23 Indian nsSNPs of the RAS pathway genes were selected for structural analysis and 8 were predicted to be damaging. Further sequence analysis showed that HEMGH zinc binding motif changes to HEMGD in somatic ACE-C domain (sACE-C) H992D and Testis ACE (tACE) H418D resulted in loss of zinc coordination, which is essential for enzymatic activity in this metalloprotease. There was a loss of internal interactions around the zinc coordination residues in the protein structural network. This was also confirmed by Principal Component Analysis, Free Energy Landscape and residue contact maps. Both mutations lead to broadening of the AngI binding cavity. The H992D mutation in sACE-C is likely to be favorable for cardiovascular health, but may lead to renal abnormalities with secondary impact on the heart. H418D in tACE is potentially associated with male infertility. Communicated by Ramaswamy H. Sarma