Renal Abnormalities Research Articles

LncRNA CASC2 Alleviates Renal Interstitial Inflammation and Fibrosis through MEF2C Downregulation-Induced Hinderance of M1 Macrophage Polarization

Introduction: Long noncoding RNA (lncRNA) cancer susceptibility candidate 2 (CASC2) alleviates the progression of diabetic nephropathy by inhibiting inflammation and fibrosis. This study investigated how CASC2 impacts renal interstitial fibrosis (RIF) through regulating M1 macrophage (M1) polarization. Method: Nine-week-old mice underwent unilateral ureteral obstruction (UUO) establishment. Macrophages were induced toward M1 polarization using lipopolysaccharide (LPS) in vitro and cocultured with fibroblasts to examine how M1 polarization influences RIF. LnCeCell predicted that CASC2 interacted with myocyte enhancer factor 2 C (MEF2C), which was validated by dual-luciferase reporter assay. CASC2/MEF2C overexpression was achieved by lentivirus-expressing lncRNA CASC2 injection in vivo or CASC2 and MEF2C transfection in vitro. Renal injury was evaluated through biochemical analysis and hematoxylin-eosin/Masson staining. Macrophage infiltration and M1 polarization in the kidney and/or macrophages were detected by immunofluorescence, flow cytometry, and/or quantitative reverse transcription polymerase chain reaction (qRT-PCR). Expressions of CASC2, MEF2C, and markers related to inflammation/M1/fibrosis in the kidney/macrophages/fibroblasts were analyzed by qRT-PCR, fluorescence in situ hybridization, enzyme-linked immunosorbent assay, and/or Western blot. Result: In the kidneys of mice, CASC2 was downregulated and macrophage infiltration was promoted time-dependently from days 3 to 14 post-UUO induction; CASC2 overexpression alleviated renal histological abnormalities, hindered macrophage infiltration and M1 polarization, downregulated renal function markers serum creatinine and blood urea nitrogen and inflammation/M1/fibrosis-related makers, and offset UUO-induced MEF2C upregulation. LncRNA CASC2 overexpression inhibited fibroblast fibrosis and M1 polarization in cocultured fibroblasts with LPS-activated macrophages. Also, CASC2 bound to MEF2C and inhibited its expression in LPS-activated macrophages. Furthermore, MEF2C reversed the inhibitory effects of lncRNA CASC2 overexpression. Conclusion: CASC2 alleviates RIF by inhibiting M1 polarization through directly downregulating MEF2C expression. CASC2 might represent a promising value of future investigations on treatment for RIF.

A novel genotype-phenotype between persistent-cloaca-related VACTERL and mutations of 8p23 and 12q23.1.

The mechanism underlying anorectal malformations (ARMs)-related VACTERL (vertebral defects, anal atresia, cardiac defects, tracheo-esophageal fistula, and renal and limb abnormalities) remains unclear. Copy number variation (CNV) contributed to VACTERL pathogenicity. Here, we report a novel CNV in 8p23 and 12q23.1 identified in a case of ARMs-related VACTERL association. This 12-year-old girl presented a cloaca (urethra, vagina, and rectum opening together and sharing a single tube length), an isolated kidney, and a perpetuation of the left superior vena cava at birth. Her intelligence, growth, and development were slightly lower than those of normal children of the same age. Array comparative genomic hybridization revealed a 9.6-Mb deletion in 8p23.1-23.3 and a 0.52-Mb duplication in 12q23.1 in her genome. Furthermore, we reviewed the cases involving CNVs in patients with VACTERL, 8p23 deletion, and 12q23.1 duplication, and our case was the first displaying ARMs-related VACTERL association with CNV in 8p23 and 12q23.1. These findings enriched our understanding between VACTERL association and the mutations of 8p23 deletion and 12q23.1 duplication. IMPACT: This is a novel case of a Chinese girl with anorectal malformations (ARMs)-related VACTERL with an 8p23.1-23.3 deletion and 12q23.1 duplication. Cloaca malformation is presented with novel copy number variation in 8p23.1-23.3 deletion and 12q23.1 duplication.

The prevalence and associated risk factors of detectable renal morphological abnormalities in acromegaly.

The aim of this study was to investigate the prevalence of simple renal cysts (SRCs) and kidney stone disease (KSD) together with laboratory data in patients with acromegaly through comparisons with healthy subjects, and to examine the possible risk factors associated with these abnormalities in acromegaly. This retrospective, single-center study included 125 acromegaly patients (46.4 ± 11.6 years, 68 females/57 males) and 114 age-sex matched healthy individuals (45.3 ± 12.4 years, 59 females/55 males). Demographic data, clinical history, biochemical and abdominal/urinary system ultrasonographic data of the patients were reviewed. The SRC prevalence (28.8% vs. 8.8%, p < 0.001) and the longitudinal and transverse lengths of kidneys (p < 0.05) were significantly higher in patients with acromegaly compared to the control group. The presence of acromegaly was determined to increase the risk of SRC formation 12.8-fold. The prevalence of KSD was similar in both the patient and control groups (15.2% vs. 7.9%, p = 0.08). Patients with acromegaly with renal cysts (n = 36) compared to the group without cysts (n = 89) were older, had a higher male gender frequency, a longer pre-diagnosis symptom duration, and a higher incidence of hypertension and diabetes mellitus at the time of diagnosis. The multivariate logistic regression analysis showed that only advanced age and male gender were associated risk factors for SRCs in acromegaly patients. The results of this study showed that acromegaly disease significantly increased the prevalence of SRCs and kidney length compared to the age-sex matched healthy population, while the prevalence of KSD was similar. Advanced age and male gender were seen to be independent risk factors for SRC formation in patients with acromegaly.

Renoprotective Effect of Thymoquinone against Streptozotocin-Induced Diabetic Nephropathy: Role of NOX2 and Nrf2 Signals.

Diabetic nephropathy is an unavoidable complication of chronic uncontrolled diabetes mellitus. The pathogenesis of diabetic nephropathy is multifactorial, and the development of an effective therapy remains to be elucidated. The aim of the present study was to assess the role of NOX2 and Nrf2 in the protective mechanism of thymoquinone (THQ) against streptozotocin (STZ)-induced diabetic nephropathy. Rats were injected with STZ (55 mg/kg) to induce diabetes. The diabetic rats were orally treated with THQ (10 mg/kg/day) for eight weeks. STZ-treated rats exhibit an elevation of serum creatinine, serum urea, and creatinine clearance. The renal abnormalities were associated with increased NADPH oxidase isoform, NOX2 protein expression, and activity, along with elevated malondialdehyde (MDA). In addition, the tumor necrotic factor-alpha (TNF-α) level and nitric oxide (NO) bioavailability, as well as the transforming growth factor-beta (TGF)-β, were markedly increased. On the other hand, the nuclear factor-E2-related factor (Nrf2) protein expression was significantly reduced in diabetic rats compared to the control. However, treatment with THQ significantly reversed these alterations with subsequent ameliorating renal dysfunction and pathological abnormalities. The present study demonstrates that THQ could protect against STZ-induced diabetic nephropathy by modulating the Nrf2/NOX2 signaling pathway.

Considering Older Patients As Candidates for Auto Stem Cell Transplants: A Comprehensive Study on Toxicities and Survival Analysis

Introduction: High-dose chemotherapy and autologous stem cell transplantation (ASCT) are commonly used for relapsed/refractory (R/R) Hodgkin (HL) and non-Hodgkin lymphoma (NHL). However, concerns about treatment-related mortality (TRM) and toxicity limit its use in older patients (pts). Existing evidence suggests higher rates of complications and inferior overall survival (OS) in older pts, but conflicting findings suggest that outcomes may be influenced by comorbidities rather than age ( Lahoud O, Curr Oncol Rep. 2015). Our study comparing ASCT outcomes and toxicities in lymphoma pts in younger and older age groups. Methods: In this retrospective study, we analyzed lymphoma pts who underwent ASCT at the Princess Margaret Cancer Centre from January 2015 to December 2019. After Institutional Review Board approval, clinical data was collected from institutional databases and patient charts. The hematopoietic cell transplantation comorbidity index (HCT-CI) and Charlson Comorbidity Index (CCI) were retrospectively calculated. Response assessment was done by Lugano 2014 classification. Grade 3-5 nonhematologic toxicities were collected from admission to day 100 using Common Terminology Criteria for Adverse Events version 5. Overall survival (OS) and progression-free survival (PFS) were calculated from date of transplant to death or disease progression. OS and PFS assessed via Kaplan-Meier; log rank tests and Cox regression performed. The patients were divided into two age groups: Group A (&amp;lt;65 years) and Group B (≥65 years). Results: There were 334 pts who underwent ASCT. 332 pts were analyzed; 2 pts were lost to follow-up and 16 pts were day 1 transfers, making acute toxicity data unavailable. The median age was 53 (range: 18-71), 17% of pts being aged ≥65. The majority of pts (69%) had NHL (table 1). The Eastern Cooperative Oncology Group (ECOG) performance status was ≤1 for 91%. Group B had a higher proportion of pts with ECOG score =2 (18% vs 7%, p &amp;lt; 0.001 ) and higher CCI (88% vs 27% , p &amp;lt; 0.001). NHL and mantle cell lymphoma (MCL) were more prevalent in Group B (93%, 23% vs 68%, 12% respectively, p&amp;lt; 0.001). Thirteen percent of NHL pts were transformed disease. Both groups had similar percentage of pts with central nervous system (CNS) lymphoma (~ 5%). Conditioning regimens varied based on lymphoma type: most of the HL/aggressive lymphomas: Etoposide+Melphalan (ML), CNS lymphoma: Thiotepa based regimen, and MCL Cytarabine + ML+/- Total Body Irradiation. The majority (83%) were treated for R/R disease, while 17% received it as first-line treatment. Prior to transplant, 76% of pts were in CR. Median follow-up was 38 months. Median OS was not reached for Group A, and 73 months for Group B. Five year OS were 82% and 74% respectively (p = 0.05). Median PFS was 75.2 months for Group A and 43.0 months for Group B, with 5-year PFS of 54% and 47% respectively (p = 0.2). Twenty percent of pts died during follow-up, with only 4% being NRM. From the entire cohort 3% of patients died within 100 days post-transplant, with no difference between groups. Three pts died within 100 days of ASCT with 2 deaths from sepsis (Group A) and 1 death from Respiratory failure (Group B). Common transplant-related toxicities did not differ significantly between groups (figure 1). Group B had significantly higher rates of Renal (7%vs 18%), Respiratory (16% vs 6%), and Metabolism abnormalities (14% vs 5%) (p = 0.021-0.028). Group B needed more blood product transfusions by 100 days post-transplant: Packed Cells (mean) 1.7 vs 1.1 units (p 0.08), Platelets (mean) 3 vs 1.9 units (p 0.002). Group B had a longer average length of stay 18 days vs. 14 days (p &amp;lt; 0.001). About 6% of pts required ICU admission, and 4% were discharged to rehabilitation/long-term care facilities, with no group differences. Conclusions: The study concludes that ASCT can be safely performed in appropriately selected elderly pts. TRM rates were not significantly higher in older compared to younger pts with lymphoma. However, older pts did experience higher rates of specific toxicities including renal failure, pulmonary complications, metabolism abnormalities, longer hospital stays, and increased transfusion requirements. In the multivariate analysis, older pts exhibited shorter OS, influenced by lymphoma type and treatment response. Further research is needed to develop risk stratification and geriatric assessments to improve toxicity prediction in elderly pts undergoing ASCT.

Validation of Townes As Mice As a Model of Chronic Kidney Disease and Venous Thrombosis Associated with Sickle Cell Trait

Individuals with sickle cell trait (SCT) are heterozygous carriers of the sickle beta-globin gene. Systematic analyses of large cohort studies over the past decade have established that SCT is a risk factor for a limited number of complications, most notably chronic kidney disease (CKD) and venous thrombosis (VT). SCT red blood cells (RBCs) can undergo sickling, although the degree and duration of hypoxia required to produce sickling are much greater than in sickle cell disease due to the lower intra-erythrocyte sickle hemoglobin beta (HbS) concentration of 25-45%. Hypoxia-mediated HbS polymerization can be enhanced by cellular dehydration, hyperosmolarity and/or acidosis that may be encountered in the renal inner medulla. Furthermore, prolonged exposure of SCT RBCs to profound hypoxia, such as in the nidus of a venous clot, will also result in sickling. The objective of this study was to determine if Townes AS mice manifest kidney dysfunction analogous to their SCT human counterparts. Furthermore, we evaluated whether VT was more pronounced in a well-described model of inferior vena cava (IVC) stasis. We used humanized male sickle cell trait (AS) and age-matched genetic control (AA) mice (n=7-16). Analysis of urinary renal biomarkers (albuminuria, proteinuria, kidney injury marker 1 (KIM-1), osmolality) and kidney function (transcutaneous measurement of glomerular filtration rate (GFR)) were conducted at 4-week intervals from 8 to 40 weeks of age. VT was induced by complete occlusion of the IVC in AA and AS mice. Sickling of RBCs was determined by histological and electron microscopy analysis of the IVC clot. Senicapoc, an oral Gardos channel inhibitor, was administered twice daily (20mg/kg, bid) for 2 weeks to prevent AS RBC dehydration and subsequent sickling. Human HbS accounts for 30.1% of total Hb expression in AS mice. Consistent with human SCT, peripheral blood counts did not differ from AA controls. Basal plasma thrombin-antithrombin complex levels were also not different between AA and AS mice. We performed a longitudinal study of renal structure and function in AA and AS mice over 40 weeks. At 8 weeks of age, AS mice exhibited no differences in any parameter compared to AA controls. However, AS mice subsequently developed albuminuria and a moderate but statistically significant increase in GFR (Figure 1). At 36 and 40 weeks of age, we observed progressive loss of kidney function demonstrated by statistically significant decreased GFR accompanied by a significant increase in albuminuria in AS mice (Figure 1). Over time, proteinuria gradually increased in AS mice, and had doubled by 40 weeks of age compared to AA controls (4.6 ±1.1 vs. 2.3 ±0.4 mg/24h, p&amp;lt;0.05). Increased levels of urinary KIM-1, a marker of tubular damage, were observed in AS mice throughout the duration of the study, with the highest levels at 16 weeks (228.3 ± 32.6 pg/24h vs. 53.8 ± 8.5 pg/24h, respectively, p˂0.05). Urine osmolality was not different at 8 weeks of age, but progressively declined in AS mice with statistically significant changes vs. controls starting at 24 weeks until the end of study (1946 ±63 vs. 2672 ±135 mOsm/kg at 40 weeks, p=0.002). Histologic analysis confirmed glomerular injury (congestion, glomerulosclerosis) and tubular injury (medullary congestion, interstitial fibrosis) in 40 week old AS mice. Following 24 hours of IVC stasis, thrombus weight was significantly increased (p&amp;lt;0.01) in AS mice (mean±SEM; 29.0 mg +/- 1.7; n=8) compared to AA controls (20.0 mg ± 1.7; n=7). Histologic and electron microscopic evaluation demonstrated that severe hypoxia (pO 2 ≈ 10 mm Hg) present in the nidus of venous thrombi was associated with extensive sickling of RBCs in AS mice. To determine if the enhancement of VT observed in AS mice was mediated by RBC sickling, mice were pretreated with Senicapoc or vehicle. Compared to vehicle-treated AS mice (27.3 mg ± 2.2 n=9) pre-treatment with Senicapoc significantly reduced (p&amp;lt;0.05) clot weight (18.1mg ± 1.1; n=7) to that observed in untreated AA controls. In aggregate, our data demonstrate that Townes AS murine nephropathy closely mimics the renal abnormalities (impaired urinary concentration and albuminuria with later onset loss of GFR) described in humans with SCT. Furthermore, we have established a mouse model of the venous thrombotic complications associated with SCT and have demonstrated that hypoxia-induced sickling of RBCs may contribute to enhanced VT observed in AS mice.

Gypenoside XVII attenuates renal ischemia-reperfusion injury by inhibiting endoplasmic reticulum stress and NLRP3 inflammasome-triggered pyroptosis

BackgroundRenal ischemia-reperfusion (I/R) is one of the main causes of acute kidney injury (AKI), for which there is currently no effective treatment. Recently, the interaction between endoplasmic reticulum (ER) stress and pyroptosis during AKI has been investigated. AimThe purpose of this study was to investigate the protective effects of Gypenoside XVII (GP-17) against I/R-induced renal injury. MethodsIn this study, mice were divided into 6 groups, sham group, I/R group, GP-17 low-, medium-, high-dose group, and positive control 4-PBA group. The renal I/R was performed in mice by clamping the bilateral renal pedicles for 40 min, and then reperfusing for 24 h. Blood and kidney samples were collected for analysis. ResultsThe results showed that GP-17 improved renal function and alleviated renal histopathological abnormalities caused by I/R. In addition, GP-17 pretreatment significantly decreased the expression or phosphorylation of ER stress response proteins including BIP, p-PERK, and CHOP. Besides, GP-17 inhibited the expression of pyroptosis proteins including caspase-1, GSDMD, and apoptotic protein BAX. The inflammatory factor IL-1β in these GP-17 pretreatment groups was also significantly reduced. ConclusionGP-17 blocked NLRP3 inflammasome activation by inhibiting ERS, thereby inhibiting renal tubular cell pyroptosis and apoptosis, and prevented renal I/R injury.

Bardet-Biedl Syndrome: A Comprehensive Review of an Autosomal Recessive Ciliopathy

Bardet-Biedl Syndrome (BBS) is a rare, genetically heterogeneous, and autosomal recessive ciliopathy characterized by a complex clinical phenotype. This article provides a comprehensive review of BBS, exploring its genetic underpinnings, clinical manifestations, molecular mechanisms, and emerging therapeutic strategies. BBS is associated with primary ciliary dysfunction, leading to a spectrum of clinical features, including obesity, retinal degeneration, renal abnormalities, polydactyly, and cognitive impairments. Understanding the intricate molecular pathways involved in BBS pathogenesis, such as the role of the BBSome and the ciliary transition zone, is crucial for developing targeted treatments. This review also discusses recent advances in the field, including the potential application of gene therapy and small molecule interventions. The aim of this article is to consolidate current knowledge on BBS, shedding light on the complexities of this rare genetic disorder and the potential avenues for future research and therapeutic development.

The Second Case of Bardet-Biedl syndrome from Iraq: An educational article and expert opinion

Background: Bardet-Biedl syndrome and Laurence-Moon syndrome are rare autosomal recessive disorders with a similar phenotype. They are characterized by the gradual development of phenotype which includes cone-rod retinal dystrophy, obesity, and hypogonadism in males. Other associated abnormalities include learning disability and renal abnormalities. The two conditions are differentiated clinically by the presence of spasticity and the absence of polydactyly in Laurence-Moon syndrome. In 2002, we reported the first patient with Bardet-Biedl syndrome. The boy had polydactyly, obesity, retinal degeneration, and was hospitalized at the University Hospital in Al-Kadhimiyia because of the development of chronic renal failure. Patients and methods: The case of a 9-year-old obese Kurdish girl who had polydactyly of the hands and feet associated with reduced visual acuity is described.Results: A 9-year-old obese Kurdish girl had polydactyly of the hand and feet associated with reduced visual acuity that was attributed to myopia which was partially corrected with eye glasses. The parents were unrelated, and her younger 5-year sister had polydactyly of the feet only. No other family member known to have polydactyly. Both sisters had their extra-digits removed surgically. The girl was studying at fourth grade primary school and the parents reported no learning disability. Fundoscopy showed normal optic disc and periphery of the retina. The presence of retinitis pigmentosa was excluded. However, the foveal reflex was reported to be abnormal by the oophthalmologist. Electroretinography showed evidence of cone-rod dystrophy.Conclusion: The second case of Bardet-Biedl syndrome from Iraq is reported. The current evidence-based expert opinion suggests the use of long tem supplementation of citicoline, co-enzyme Q10 and lutein with hope of retarding the progression to blindness.

Efficacy and safety of telitacicept in patients with systemic lupus erythematosus: a multicentre, retrospective, real-world study

ObjectiveTo examine the efficacy and safety of telitacicept in the treatment of patients with SLE in everyday clinical practice.MethodsSeventy-two patients with active SLE who received telitacicept for more than 24...

Clinical application of 99mTc-DTPA dynamic renal scintigraphy with consequent SPECT/CT imaging in patients with different nephrological conditions

Introduction: Dynamic renal scintigraphy with 99mTechnetium diethylenetriaminepentaacetic acid (99mTc DTPA) is a generally used imaging technique for evaluating renal function of patients with various nephro-urological conditions. Clinical application of SPECT/CT nephroscintigraphy has rarely been discussed. Objective: The aim of the study was to evaluate the added value of SPECT/CT imaging to dynamic renal scintigraphy with 99mTc DTPA. Materials and Methods: Thirty two patients (66% female and 34% male) who underwent dynamic nephroscintigraphy with subsequent SPECT/CT with mean age 55.9±18.25 years was observed. The CT scan was performed with a low dose protocol. A dose of 185MBq (5mCi) 99mTc DTPA was administered intravenously. Results: Our analysis demonstrated impaired relative renal function in various degrees of left kidney in 18 patients (56%) and of right kidney in 14 patients (44%). SPECT/CT imaging revealed the specific cause, responsible for the renal dysfunction in the cases. The hybrid imaging demonstrated urolithiasis in 11 patients, postopertative strictures of ureter in 5 patients, diagnosed urological cancer in 4 patients, external compression of ureter from ovarian cyst in 1 patient and compression of ureter due to nephroptosis in 1 patient as a possible obstructive cause. In 10 patients congenital renal anomalies were the identified causes of impaired renal function – 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: The combination of conventional 99mTc DTPA dynamic renal scintigraphy with subsequent SPECT/CT could provide not only functional but also anatomical information of the urinary tract, especially in the evaluation of obstructive uropathies and congenital renal abnormalities, that can change the clinical management

Efficacy and safety of utidelone plus capecitabine in advanced first-line therapy for metastatic breast cancer: A multicenter real-world study

BackgroundThe purpose of this study was to compare the efficacy and safety of utidelone plus capecitabine for advanced first-line versus second-line or above therapy in metastatic breast cancer patients who had previously received anthracycline and taxane. At the same time, we compared the efficacy of utidelone plus capecitabine and vinorelbine plus cisplatin in advanced first-line treatment of metastatic breast cancer. Patients and methodsA retrospective cohort of 11 patients with metastatic breast cancer previously treated with anthracycline and taxane (including neoadjuvant and adjuvant therapies) for advanced first-line with utidelone plus capecitabine, 32 patients treated with second-line or above, and 60 patients with vinorelbine plus cisplatin between October 2011 and August 2022 was collected. The first and second groups were treated with utidelone plus capecitabine, and the third group was treated with vinorelbine plus cisplatin. The primary endpoint was progression-free survival (PFS), and secondary endpoints were overall survival (OS), objective response rate (ORR), and treatment safety. ResultsBy 03/31/2023, median PFS reached 11.70 months (95 % CI 0.093–0.141) in utidelone plus capecitabine group in the advanced first-line therapy, compared to 5.60 months (95 % CI 0.025–0.079) in the second-line or above therapy [HR 0.42, (95 % CI 0.226–0.787), P = 0.0077]. In utidelone plus capecitabine, the median OS was not reached in the advanced first-line therapy, with a mean overall survival of 23.16 months (95 % CI 0.198–0.265); whereas the median OS in the second-line or above therapy was 19.50 months (95 % CI 0.083–0.307), with a mean overall survival of 16.89 months (95 % CI 0.136–0.202) [HR 0.26, (95 % CI 0.098–0.678), P = 0.0495]. The ORR for advanced first-line therapy was 27.27 % (95%CI 0.060, 0.610) compared with 15.63 % (95%CI 0.053, 0.328) for second-line or above. In advanced first-line therapy, utidelone plus capecitabine was superior to vinorelbine plus cisplatin with a median PFS of 6.12 months (95 % CI 0.051–0.072) [HR 0.49, (95 % CI 0.286–0.839), P = 0.0291]. Compared with utidelone plus capecitabine, the median OS in vinorelbine plus cisplatin advanced first-line therapy group was 35.37 months (95 % CI 0.258–0.449), and the mean overall survival was 40.79 months (95 % CI 0.315–0.501) [HR 0.54, (95 % CI 0.188–1.568), P = 0.2587]. The ORR for vinorelbine plus cisplatin was 18.33 % (95 % CI 0.095, 0.304). The most common adverse events in our study were neurological toxicity, hand-foot syndrome, hematological toxicity, gastrointestinal toxicity, and hepatic and renal function abnormalities. There were no deaths due to adverse effects during the utidelone plus capecitabine treatment period. ConclusionsIn MBC, advanced first-line therapy with utidelone plus capecitabine resulted in more favorable PFS, OS, and ORR than second-line or above therapy. In advanced first-line therapy, utidelone plus capecitabine had superior PFS, and ORR compared with vinorelbine plus cisplatin. This study concludes that utidelone plus capecitabine is a more valuable chemotherapy option in advanced first-line MBC.

Sequence variants in different genes underlying Bardet-Biedl syndrome in four consanguineous families.

Bardet-Biedl Syndrome (BBS) is a rare (1:13,500-1-160,000) heterogeneous congenital disorder, characterized by postaxial polydactyly, obesity, hypogonadism, rod-cone dystrophy, cognitive impairment, and renal abnormalities (renal cystic dysplasia, anatomical malformation). To date about twenty-five genes have been identified to cause BBS, which accounts for about 80% of BBS diagnosis. In the current study, we have performed mutational screening of four Pakistani consanguineous families (A-D) with clinical manifestation of BBS by microsatellite-based genotyping and whole exome sequencing. Analysis of the data revealed four variants, including a novel/unique inheritance pattern of compound heterozygous variants, p.(Ser40*) and p.(Thr259Leufs*21), in MKKS gene, novel homozygous variant, p.(Gly251Val)] in BBS7 gene and two previously reported p.(Thr259Leufs*21) in MKKS and p.(Met1Lys) in BBS5 gene. The variants were found segregated with the disorder within the families. The study not only expanded mutations spectrum in the BBS genes, but this will facilitate diagnosis and genetic counselling of families carrying BBS related phenotypes in Pakistani population.

Dimethyl Fumarate Ameliorated Cardiorenal Anemia Syndrome and Improved Overall Survival in Dahl/Salt-Sensitive Rats.

Cardiovascular disease, chronic kidney disease, and anemia are known to adversely affect each other. Inflammation is commonly involved in these diseases. Cardiorenal anemia syndrome (CRAS) is the name given to this mutually harmful condition. Dimethyl fumarate (DMF) is a Food and Drug Administration-approved antioxidant and anti-inflammatory agent. The purpose of this study was to investigate the effects of DMF on Dahl/salt-sensitive (DS) rats as a CRAS model. Six-week-old DS rats were divided into three groups: the control group, the high-salt (HS) group, and the HS+DMF group. The HS and HS+DMF groups were fed a high-salt diet (8% NaCl) from 6 weeks of age. In the HS+DMF group, DMF (90 mg/kg per day) was orally administered from 6 to 15 weeks of age. Systolic blood pressure was measured every 2 weeks. The heart and renal injuries were assessed with histopathological analysis. The heart and renal expression of mRNAs was assessed by reverse-transcription polymerase chain reaction. DMF significantly improved overall survival, which was shortened by HS in DS rats. Systolic blood pressure increased in the HS group compared with the control group, and DMF tended to suppress this change. DMF ameliorated the cardiac and renal abnormalities confirmed in the HS group by histopathological analysis. Furthermore, the changes in mRNA expressions associated with disease exacerbation in the HS group were suppressed by DMF. DMF also improved anemia. This study suggests that DMF improves overall survival in DS rats through organ-protective effects and is effective against cardiorenal anemia syndrome. SIGNIFICANCE STATEMENT: Dimethyl fumarate was found to improve overall survival in Dahl/salt-sensitive rats, associated with its ability to ameliorate anemia and induce cardioprotective and renoprotective effects through anti-inflammatory and antifibrotic effects.

Two non-familial cases of Galloway-Mowat syndrome carrying the homozygous mutations of WDR73 and TP53RK

Galloway–Mowat syndrome (GAMOS) is a rare hereditary disease manifested as a combination of nephrotic syndrome and central nervous system impairment. To date, many GAMOS cases attributed to various gene mutations have been reported such as WHAMM, NUP107, WDR73, OSGEP, and TP53RK. We detected two novel homozygous mutations of WDR73 ‘’NM_032856:c.G287A:p.R96K‘’ and TP53RK ‘’NM_033550:c.A193O:p.K65Q‘’ in two female kids of the consanguineous parents from different families using whole exome sequencing. Both patients almost manifested similar neurodegenerative phenotypes, including developmental delay, microcephaly, hypotonia, and brain atrophy on magnetic resonance imaging during infancy. WDR73-positive GAMOS case manifested a late-onset minimal nephrotic syndrome at the age 4 years while TP53RK-positive case presented nephrotic syndrome at the age 1 which progressed to steroid-resistant nephrotic syndrome due to lack of remission after 4-6 weeks of initial treatment with prednisone. Despite the brain abnormalities and the onset time difference of renal abnormalities, both patients are still alive. Given the heterogeneity of the renal phenotype among GAMOS types, accurate recognition of expanding spectrum of phenotype findings and regular renal function screening are necessary for an early diagnosis and timely treatment.

Endocrine causes of hypertension: literature review and practical approach.

Hypertension (HTN) affects more than 30% of adults worldwide. It is the most frequent modifiable cardiovascular (CV) risk factor, and is responsible for more than 10 million death every year. Among patients with HTN, we usually distinguish secondary HTN, that is HTN due to an identified cause, and primary HTN, in which no underlying cause has been found. It is estimated that secondary hypertension represents between 5 and 15% of hypertensive patients [1]. Therefore, routine screening of patients for secondary HTN would be too costly and is not recommended. In addition to the presence of signs suggesting a specific secondary cause, screening is based on specific criteria. Identifying secondary HTN can be beneficial for patients in certain situations, because it may lead to specific treatments, and allow better control of blood pressure and sometimes even a cure. Besides, it is now known that secondary HTN are more associated with morbidity and mortality than primary HTN. The main causes of secondary HTN are endocrine and renovascular (mainly due to renal arteries abnormalities). The most frequent endocrine cause is primary aldosteronism, which diagnosis can lead to specific therapies. Pheochromocytoma and Cushing syndrome also are important causes, and can have serious complications. Other causes are less frequent and can be suspected on specific situations. In this article, we will describe the endocrine causes of HTN and discuss their treatments.

Analysis of factors associated with severe bleeding after percutaneous nephrolithotomy and evaluation of interventional embolization efficacy in male patients

Objective: To explore the factors associated with severe bleeding after percutaneous nephrolithotomy (PCNL) in male patients and evaluate the efficacy of interventional embolization. Methods: A retrospective case series study was conducted at Nankai Hospital of Tianjin, China, from January 2018 to October 2021. The clinical data of 230 male patients with upper urinary tract stones were analyzed. The observation indicators included age, hypertension, diabetes, renal function abnormalities, history of preoperative anticoagulant use, stone size, stone type, number of puncture channels, operation time and degree of hydronephrosis. To describe the clinical characteristics of bleeding after percutaneous nephrolithotomy in men, and analyze the factors associated with severe bleeding after PCNL. Single factor analysis was performed using the Chi-square (χ2) test, and multivariate analysis was performed using logistic regression analysis. Results: Univariate analysis showed that diabetes mellitus (χ2=4.90, P=0.027), abnormal renal function (χ2=18.32, P<0.001), history of preoperative oral anticoagulants (χ2=5.10, P=0.024), abnormal bleeding and coagulation function (χ2=8.22, P=0.004) and the number of puncture channels (χ2=22.08, P<0.001) were the related factors affecting bleeding after PCNL. Multivariate logistic regression analysis showed that diabetes mellitus (P=0.032), abnormal renal function (P<0.001), and the number of puncture channels (P<0.001) were the independent risk factors of bleeding after PCNL. Of the 28 patients with bleeding after PCNL, 25 were treated with interventional embolization, with a technical success rate of 100.0% and a clinical success rate of 89.3%. Conclusions: For patients with renal calculi and comorbid diabetes, renal function abnormalities, and multiple punctures, relevant preventive measures should be actively administered before PCNL to reduce the risk of postoperative bleeding. For patients with severe bleeding of the kidney after PCNL, TAE is a safe and effective minimally invasive treatment method.

Diverse ultrasound image features of unilateral genital tract obstruction with ipsilateral renal anomaly syndrome on genitourinary system segmental sequential ultrasound screening and the accuracy of ultrasonic diagnosis.

Unilateral genital tract obstruction with ipsilateral renal anomaly (UGTOIRA) syndrome is a rare congenital urogenital anomaly, characterized by different combinations of uterine abnormalities, unilateral cervical-vaginal obstruction, and ipsilateral renal abnormalities. Timely and correct diagnosis is critical. In this study, we analyzed the diverse ultrasound image features of UGTOIRA syndrome on genitourinary system segmental sequential ultrasound screening (SSUS) and the accuracy of ultrasonic diagnosis. The data from 59 patients with UGTOIRA syndrome over the last decade were analyzed retrospectively, which included ultrasound presentations and diagnoses of abnormalities of the uterus, cervix, and vagina, as well as the conditions associated with the bilateral fallopian tubes, ovaries, pelvis, kidneys and ureters, bladder, and urethra. All 59 patients (100%) were found to have ipsilateral renal agenesis, and the diagnostic accuracy of ultrasound was 100%. The uterus was correctively diagnosed as complete bicorporal uterus in 42 cases (71.2%), bicorporal septate uterus in 7 cases (11.9%), complete uterus septate in 8 cases (13.6%), partial uterus septate in 1 case (1.7%), and unilateral isthmus atresia in 1 case (1.7%). The cervix was correctively diagnosed as septate cervix in 28 cases (47.5%), double cervix in 17 cases (28.8%), unilateral small cervix in 5 cases (8.5%), unilateral obliterated cervical orifice in 5 cases (8.5%), partial development of the unilateral cervix with a blind end in 3 cases (5.1%), and unilateral completely undeveloped cervix appearing as a normal cervix in 1 case (1.7%). The vagina was correctively diagnosed as oblique vaginal septum (OVS) in 45 cases (76.3%), and normal vagina in 13 cases (22.0%) via preoperative ultrasound. In 1 case (1/59, 1.7%) of high OVS with ipsilateral obliterated external cervical orifice, the OVS was missed by preoperative ultrasound. The ultrasound diagnostic accuracy rates of uterine malformation, cervical malformation, vaginal malformation, hematoma location and volume, uterine communication, and cervical communication were respectively 100%, 100%, 98.3%, 100%, 100%, and 100%. The ultrasonic detection rate for a hole on the OVS was 0%, and the missed diagnosis rate was 100%. SSUS can be used to accurately evaluate uterine, cervical, and vaginal malformation, obstruction site, location and volume of keratocele, cervical or uterine communication, and ovarian endometriosis cyst in patients with UGTOIRA syndrome and ipsilateral urinary system malformation. However, ultrasound is unable to identify a hole on the OVS.

EP12.10: Flow Viewer enhances colour flow and aids in the diagnosis of a fetal renal abnormality

EP12.10: Flow Viewer enhances colour flow and aids in the diagnosis of a fetal renal abnormality

Managing Cancer Treatment in Patients with Renal Dysfunction: The Role of Chemotherapy.

Malignancy is characterized by damage to several vital organs, and utilizing chemotherapy as a treatment option can have toxic effects on healthy body tissues. Kidney function is commonly compromised by cancer and chemotherapy. These effects can be pre-renal, intrarenal, or postrenal. Tumor lysis syndrome and electrolyte disturbances are also common in this group of patients. Etiologies of this dysfunction are poorly understood; therefore, careful monitoring and management of renal function are required in such cases. This narrative review aimed to highlight some of the common renal abnormalities among patients receiving cancer and chemotherapy.