Renal Structural Abnormalities Research Articles

Medical Findings in Infants Prenatally Identified with Sex Chromosome Trisomy in Year One of Life.

Sex chromosome trisomies (SCT), including XXY, XYY, and XXX syndromes, have been historically underdiagnosed. Noninvasive prenatal cell-free DNA screening has significantly increased identification of these conditions, leading to a need for pediatric care for a growing population of newborns with SCT. Our goal was to analyze and compare perinatal features, medical diagnoses, and physical features in infants with prenatal identification of SCT conditions through the first year of life. The eXtraordinarY Babies Study is an ongoing, prospective natural history study of prenatally identified children with SCT conducted by interdisciplinary teams in Colorado and Delaware. Participants were enrolled prior to 12 months of age and had pregnancy, birth, medical histories, and physical exams completed by board-certified pediatricians at 2, 6, and/or 12-month visits. Descriptive statistics were followed by comparisons between SCT groups using t-tests or ANOVA, Fisher exact, and correlations between medical features with alpha of 0.05. Relative risks were calculated compared to general population rates. 327 infants were included in the analysis (XXY=195, XXX=79, XYY=53). Major congenital anomalies were rare (1.7%). Relative risk compared to general population was elevated for breastfeeding difficulties (51.7%;RR 2.7), positional torticollis (28.2%;RR 7.2), eczema (48.0%;RR 3.5), food allergies (19.3%;RR 2.4), constipation requiring intervention (33.9%;RR 7.6), small cardiac septal defects (7.7%;RR 17.2), and structural renal abnormalities (4.4%;RR 9.7). Inpatient hospitalization was required for 12.4%, with 59.5% of hospitalizations attributable to respiratory infections. These findings of medical conditions with a higher prevalence can inform anticipatory guidance and medical management for pediatricians caring for infants with SCT. Medical findings in largest cohort of prenatally identified infants with XXY, Trisomy X, and XYY from birth to 12 months and implications for pediatric care.What's Known on This Subject: One in ∼500 individuals have an extra X or Y chromosome, or sex chromosome trisomy (SCT). Prenatal screening is now routinely identifying SCT, however there are few studies to guide perinatal and infant care for these individuals.What This Study Adds: This prospective observational study presents medical features for 327 infants with prenatally identified SCT from birth through the first year of life. Results identify where proactive screenings and/or interventions may be warranted for infants with SCT.

Modulation of Sirtuin 3 by N-Acetylcysteine Preserves Mitochondrial Oxidative Phosphorylation and Restores Bisphenol A-Induced Kidney Damage in High-Fat-Diet-Fed Rats.

Bisphenol A (BPA) and high-fat diets (HFD) are known to adversely affect the kidneys. However, the combined effects of both cases on kidney health and the potential benefits of N-acetylcysteine (NAC) in mitigating these effects have not been investigated. To explore these aspects, male Wistar rats were fed with HFD and allocated to receive a vehicle or BPA. At week twelve, the BPA-exposed rats were subdivided to receive a vehicle or NAC along with BPA until week sixteen. Rats fed HFD and exposed to BPA showed renal dysfunction and structural abnormalities, oxidative stress, inflammation, and mitochondrial dysfunction, with alterations in key proteins related to mitochondrial oxidative phosphorylation (OXPHOS), bioenergetics, oxidative balance, dynamics, apoptosis, and inflammation. Treatment with NAC for 4 weeks significantly improved these conditions. The findings suggest that NAC is beneficial in protecting renal deterioration brought on by prolonged exposure to BPA in combination with HFD, and modulation of sirtuin 3 (SIRT3) signaling by NAC appears to play a key role in the preservation of homeostasis and integrity within the mitochondria by enhancing OXPHOS activity, maintaining redox balance, and reducing inflammation. This study provides valuable insights into potential therapeutic strategies for preserving kidney health in the face of environmental and dietary challenges.

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.

Kunxian capsule alleviates podocyte injury and proteinuria by inactivating β-catenin in db/db mice.

Diabetic kidney disease (DKD) remains the primary cause of end-stage renal disease (ESRD) globally, but treatment options are limited. Kunxian capsule (KXC) has been utilized for the treatment of autoimmune diseases and IgA nephropathy in China. However, its effect on DKD remains poorly investigated. Therefore, this study aimed to explore the protective effect of KXC in db/db mice and elucidate its underlying mechanism. The renoprotective effects of KXC were assessed in a DKD mouse model using male BKS db/db diabetic mice. After 8 weeks of treatment, the urinary albumin-to-creatinine ratio (UACR), blood biochemical parameters, renal histopathological manifestation, and podocyte ultrastructural changes were evaluated. Additionally, the expression of podocyte epithelial-to-mesenchymal transition (EMT) markers [WT1, ZO-1, and collogen I (Col1a1)] was quantitatively analyzed. Furthermore, we explored the role of KXC in the β-catenin signaling pathway to elucidate the underlying mechanism of KXC's renoprotective effect. KXC treatment effectively reduced albuminuria and attenuated renal structural abnormalities in db/db mice. Additionally, KXC restored the protein and mRNA expression of WT1 and ZO-1 while suppressing the expression of Col1a1 in db/db mice, indicating its ability to alleviate podocyte EMT. Mechanistically, KXC exerted a significant suppressive effect on the activation of β-catenin signaling in diabetic kidneys. KXC has the potential to protect podocytes during DKD by alleviating podocyte EMT through inactivating β-catenin signaling.

High-fat diet causes mitochondrial damage and downregulation of mitofusin-2 and optic atrophy-1 in multiple organs.

High-fat consumption promotes the development of obesity, which is associated with various chronic illnesses. Mitochondria are the energy factories of eukaryotic cells, maintaining self-stability through a fine-tuned quality-control network. In the present study, we evaluated high-fat diet (HFD)-induced changes in mitochondrial ultrastructure and dynamics protein expression in multiple organs. C57BL/6J male mice were fed HFD or normal diet (ND) for 24 weeks. Compared with ND-fed mice, HFD-fed mice exhibited increased body weight, cardiomyocyte enlargement, pulmonary fibrosis, hepatic steatosis, renal and splenic structural abnormalities. The cellular apoptosis of the heart, liver, and kidney increased. Cellular lipid droplet deposition and mitochondrial deformations were observed. The proteins related to mitochondrial biogenesis (TFAM), fission (DRP1), autophagy (LC3 and LC3-II: LC3-I ratio), and mitophagy (PINK1) presented different changes in different organs. The mitochondrial fusion regulators mitofusin-2 (MFN2) and optic atrophy-1 (OPA1) were consistently downregulated in multiple organs, even the spleen. TOMM20 and ATP5A protein were enhanced in the heart, skeletal muscle, and spleen, and attenuated in the kidney. These results indicated that high-fat feeding caused pathological changes in multiple organs, accompanied by mitochondrial ultrastructural damage, and MFN2 and OPA1 downregulation. The mitochondrial fusion proteins may become promising targets and/or markers for treating metabolic disease.

LBODP032 Case Report Of A 13 Years Old Female With A Novel Pathogenic Variant In The Hnf1b Gene

Abstract Background MODY5 results from mutations in the gene encoding hepatocyte nuclear factor 1 homeobox B (HNF1B), a transcription factor critical in development of the pancreas, liver, intestines, and the urogenital tract (1). We report the case of a pediatric patient with a novel frameshift variant (p. Phe309SerfsTer18) in the HNF1B gene accounting for the co-occurrence of diabetes mellitus and structural renal abnormalities. Clinical case: A 13-years-old female with chronic kidney disease stage 3 (eGFR = 48 ml/min/1.73m2) secondary to congenital dysplastic-appearing left kidney and surgical removal of a cystic dysplastic right kidney was referred to our diabetes clinic for hyperglycemia. She reported long-standing polyuria and polydipsia previously attributed to her kidney disease. She required laparoscopic right nephrectomy at age 5 years due to increasing cyst size. Her left kidney also has small renal parenchymal cysts which have been monitored over time. There is no known family history of kidney disease, and grandparents have a history of diabetes. Laboratory investigation revealed a random blood glucose of 478 mg/dL and a hemoglobin A1c of 12.2%. She was not in diabetic ketoacidosis. She had a detectable insulin level of 5.1 mcIU/mL and C-peptide was 3.4 ng/mL. She was initially presumed to have Type 1 diabetes based on a relatively low insulin level and started on basal-bolus insulin (up to 0.59 units/kg of weight/day). Glycosylated hemoglobin was 8.7% one month after diagnosis. Glutamic acid decarboxylase, zinc transporter, islet cell, and insulin autoantibodies were not detected, however, and she was then suspected to have either Type 2 diabetes or MODY. Approximately one year later, she was taken off insulin due to hypoglycemia and managed only with metformin 500 mg twice daily. Next-generation sequencing revealed a de novo pathogenic variant in HNF1B causing a frameshift deletion (p. Phe309SerfsTer18). Genetic testing of parents was negative. Once her diagnosis of MODY5 was made, she was started on glipizide 2.5 mg once daily which has been titrated up to a dose of 5 mg with some success. However, she has since been re-started on insulin (up to 0.2 units/kg/day) due to hyperglycemia keeping in line with the MODY5 phenotype likely causing destruction of beta cells over time (1). Conclusion We report a case of MODY5 with a novel frameshift mutation (p. Phe309SerfsTer18) in the HNF1B gene. This case highlights the importance of screening for HNF-1B mutations in those patients with structural renal abnormalities and hyperglycemia, as diagnosis can guide management decisions and provide prognostic information. Reference Bellanné-Chantelot C, Chauveau D, Gautier JF, et al. Clinical spectrum associated with hepatocyte nuclear factor-1beta mutations. Ann Intern Med. 2004;140(7): 510-517. doi: 10.7326/0003-4819-140-7-200404060-0000 Presentation: No date and time listed

Renal outcome in patients with complex anorectal malformations

Introduction: Anorectal malformations (ARMs) are one of the most frequent congenital malformations in pediatric surgery. Its estimated incidence ranges between 1 in 2000 and 1 in 5000 live newborns approximately. The aim of the work is to present the associated urinary anomalies and functional renal outcomes in patients with worse prognosis anorectal malformations treated in our department Material and methods: A retrospective review of the patients operated at our center with complex anorectal malformations was performed, including urological abnormalities and long-term renal follow-up. Collected data included the type of urinary abnormality, classified as high or low, renal function (glomerular filtration rate and blood creatinine level), the presence of chronic kidney failure (CKD), the need for surgery to correct the urinary abnormality, the need for kidney transplantation and complications and long-term results. Results: A total of 55 patients were included, 32 girls and 23 boys. Mean age at the time of corrective surgery for the anorectal malformation was 9 months (SD 2.18). The mean follow-up of the patients was 13 years (SD 7.01). Sixty-nine per cent of the patients presented some urological anomaly, being more frequent in the cloacal group. Renal structural abnormalities were found in 22 (40%) of 55 patients. They were identified in 11 (47%) cloacal patients, being the most frequent renal dysplasia (n=7; 32%), followed by position abnormalities in 3. Regarding the lower urinary tract anomalies, it was described in 32 (58%) patients. In the cloacal group, the incidence was 65%, being the most frequent vesicoureteral reflux (n = 14, 60%) as well as in the group of patients with a fistula to the prostatic urethra and in the group with exstrophies of the cloaca (n = 3, 42%). Regarding the rest of the lower urinary tract anomalies, the general incidence of anatomic bladder anomalies (bladder diverticulum, patent urachus) was 15%. As a pathology related to the upper urinary tract: primary obstructive megaureter 5%, ureterocele 1% and posterior urethral valves 1%. Conclusions: Patients with complex anorectal malformations have a significant risk for renal impairment. Adequate screening, high level of suspicion, treatment and long term follow up of any associated urinary anomaly in patients with complex anorectal malformations is essential to preserve renal function and prevent CKD. Care by a multidisciplinary team and adequate transition to adulthood is essential to optimize the medical management of patients and long-term outcomes.

MO269: The Frequency and Aetiology of Repeated Acute Kidney Injury Episodes Determines the Degree of Renal Damage

Abstract BACKGROUND AND AIMS Chronic kidney disease (CKD) is the most serious health problem and constitutes the 16th leading cause of death worldwide. Multiple studies have identified acute kidney injury (AKI) as a risk factor for the development and progression of CKD [1]. Despite extensive investigation of AKI and CKD in experimental models, the underlying mechanisms of the transition from AKI to CKD remain unclear. It is known that after an AKI episode, maladaptive responses may occur resulting in structural and fuctional abnormalities as parenchymal inflammation, tubular cell death, accumulation of extracellular matrix, and decreased glomerular filtration rate, among others [2]. We hypothesized that after the combination of different renal insults, the mechanisms of adaptative repair could be less effective causing renal structural abnormalities that might not be detected by common clinical parameters but could lead to CKD. METHOD We used 8-week-old, male Wistar rats. Animals were divided into four experimental groups: ‘Control’ group: SHAM-operated rats, which received saline solution, i.p.; ‘CDDP5-I/R’ group: 5 mg/kg cisplatin i.p., and after renal function normalization, 60-min ischemia-reperfusion to the left kidney; ‘Ctrl-I/R-I/R’ group: 60-minute renal ischemia-reperfusion to the left kidney, and 2 weeks later 60-min ischemia-reperfusion to the right kidney; ‘CDDP5-Ctrl-I/R’ group: 5 mg/kg cisplatin i.p, and 2 weeks after renal function normalization, 60-min ischemia-reperfusion. Blood and urine samples were collected at: day 0 (basal); day 4 (AKI development); day 8 (normalized renal function); day 9 (1 day after ischemia); days 56 and 90. Renal function was analyzed through the levels of plasma creatinine concentration (pCr), creatinine clearance, blood urea nitrogen and proteinuria, which were measured with colorimetric methods. Animals were sacrificed at days 56 and 90. Tissue samples were stained with Masson's trichrome, Sirius Red, Periodic Acid Schiff and Hematoxylin-–Eosin for histological analysis. RESULTS The combination of different experimental AKI episodes and the timeframe between those episodes were related to the extent of renal structural alterations, even though renal function was apparently normal. The ‘CDDP5-Ctrl-I/R’ group presented the highest level of structural abnormalities. In addition, in those groups in which an AKI was induced by CDDP5, more structural damage was detected than in the ‘Ctrl-I/R-I/R’ group. CONCLUSION The frequency of AKI episodes, the kind of insult and their combination determine the amount and degree of tissue damage which, however, is not correlated with a decline in renal function (determined by pCr or creatinine clearance, blood urea nitrogen or proteinuria). These subclinical alterations might be related to a poor prognosis and are a risk factor for the progression of CKD; therefore, new tools to determine renal function are needed to prevent the progression and mortality of the disease.

Association of prenatal renal ultrasound abnormalities with pathogenic copy number variants in a large Chinese cohort.

To assess the clinical utility of prenatal chromosomal microarray analysis (CMA) in fetuses with abnormal renal sonographic findings, and to evaluate the association of pathogenic or likely pathogenic copy number variants (P/LP CNVs) with different types of renal abnormality. This was a retrospective study of fetuses at 14-36 weeks screened routinely for renal and other structural abnormalities at the Maternal and Child Health Hospital of Guangxi Zhuang Autonomous Region. We retrieved and analyzed data from fetuses with abnormal renal sonographic findings, examined between January 2013 and November 2019, which underwent CMA analysis using tissue obtained from chorionic villus sampling (CVS), amniocentesis or cordocentesis. We evaluated the CMA findings according to type of renal ultrasound anomaly and according to whether renal anomalies were isolated or non-isolated. Ten types of renal anomaly were reported on prenatal ultrasound screening, at a mean ± SD gestational age of 24.9 ± 4.8 weeks. The anomalies were diagnosed relatively late in this series, as 64% of cases with an isolated renal anomaly underwent cordocentesis rather than CVS. Fetal pyelectasis was the most common renal ultrasound finding, affecting around one-third (34.32%, 301/877) of fetuses with a renal anomaly, but only 3.65% (n = 11) of these harbored a P/LP CNV (comprising: isolated cases, 2.37% (4/169); non-isolated cases, 5.30% (7/132)). Hyperechogenic kidney was found in 5.47% (n = 48) of fetuses with a renal anomaly, of which 39.58% (n = 19) had a P/LP CNV finding (comprising: isolated cases, 44.44% (16/36); non-isolated cases, 25.00% (3/12)), the highest diagnostic yield among the different types of renal anomaly. Renal agenesis, which accounted for 9.92% (n = 87) of all abnormal renal cases, had a CMA diagnostic yield of 12.64% (n = 11) (comprising: isolated cases, 11.54% (9/78); non-isolated cases, 22.22% (2/9); unilateral cases, 11.39% (9/79); bilateral cases, 25.00% (2/8)), while multicystic dysplastic kidney (n = 110), renal cyst (n = 34), renal dysplasia (n = 27), crossed fused renal ectopia (n = 31), hydronephrosis (n = 98), renal duplication (n = 42) and ectopic kidney (n = 99) had overall diagnostic rates of 11.82%, 11.76%, 7.41%, 6.45%, 6.12%, 4.76% and 3.03%, respectively. Compared with the combined group of CMA-negative fetuses with any other type of renal anomaly, the rate of infant being alive and well at birth was significantly higher in CMA-negative fetuses with isolated fetal pyelectasis or ectopic kidney, whereas the rate was significantly lower in fetuses with isolated renal agenesis, multicystic dysplastic kidney or severe hydronephrosis. The most common pathogenic CNV was 17q12 deletion, which accounted for 30.14% (22/73) of all positive CMA findings, with a rate of 2.51% (22/877) among fetuses with an abnormal renal finding. Fetuses with 17q12 deletion exhibited a wide range of renal phenotypes. Other P/LP CNVs in the recurrent region that were associated with prenatal renal ultrasound abnormalities included 22q11.2, Xp21.1, Xp22.3, 2q13, 16p11.2 and 1q21, which, collectively, accounted for 2.17% (19/877) of the fetuses with prenatal renal anomalies. In this retrospective review of CMA findings in a large cohort of fetuses with different types of renal ultrasound abnormality, the P/LP CNV detection rate varied significantly (3.03-39.58%) among the different types of kidney anomaly. Our data may help in the decision regarding whether to perform prenatal genetic testing in fetuses with renal ultrasound findings. Specifically, prenatal CMA testing should be performed in cases of hyperechogenic kidney, regardless of whether or not the anomaly is isolated, while it should be performed postnatally rather than prenatally in cases of fetal pyelectasis. © 2021 International Society of Ultrasound in Obstetrics and Gynecology.

Utility of Fractional Excretion of Urea (FeUrea) for differentiating AKI phenotypes in patients with cirrhosis and ascites.

Background and Aim: Acute renal failure (AKI) is a common complication of decompensated cirrhosis and confers a poor prognosis. AKI in these patients may result from functional decrease in renal function as in prerenal azotaemia (PRA) and Hepato-renal syndrome (HRS) or due to structural renal abnormalities as in acute tubular necrosis (ATN). These phenotypes of AKI have therapeutic and prognostic implications. However, in clinical practice, approaches to determine the cause of AKI in these patients are suboptimal.

Effects of endurance exercise on serum inflammatory cytokine level and kidney structure in a rat diabetes model

Diabete mellitus (DM) is becoming a global health problem. Whilst many studies have previously focused on the therapeutic effects of exercise on diabetes, insufficient data exist on its effectiveness on disease prevention. The present study was designed to evaluate the effects of endurance exercises on kidney injury and on the expression of metalloproteinases (MMPs), tissue inhibitors of metalloproteinases (TIMPs) and transforming growth factor (TGF)-β1. Type 2 diabetic rat model was created followng 8 weeks of feeding on high fat diet, followed by injection with streptozotocin (STZ; 30 mg/kg). A total of three different intensity endurance exercises, including low-intensity exercise (8 m/min and 0˚ slope), moderate-intensity exercise (15 m/min and 5˚ slope) and high-intensity exercise (20 m/min and 10˚ slope), were arranged during this process. Oral glucose tolerance (OGTT) and oral sucrose tolerance tests (OSTT) were performed in all rats 1 week after STZ injection. Serum interleukin-6 and tumor necrosis factor-α levels were measured using ELISA. After OGTT, all rats were sacrificed and kidney samples were removed for hematoxylin and eosin staining and western blot analyzes. Urea and ureatinine levels, representative of renal function, were estimated by using automatic biochemical analyzer. Rats in the DM group showed severe impaired glucose tolerance, which was alleviated in the moderate-intensity exercise (ME) and the high-intensity exercise (HE) groups. Inflammatory cytokines were also significantly reduced rats in the ME group compared with those in the DM group. No difference in renal function, MMP-9/TIMP-1 and TGF-β1 expression was observed. In addition, rats in the DM group exhibited glomerular enlargement with structural renal abnormalities, whilst those in the ME and HE groups showed improved symptoms. To conclude, no increased expression of inflammatory cytokines and renal fibrotic proteins could be observed in the present rat model of type-2 DM, but evident structural abnormalities can be observed in the kidneys. Medium-intensity endurance exercise can reduce serum inflammatory cytokine levels and prevent aberrant changes in renal structures.

Perinatal and infant outcome of fetuses with prenatally diagnosed hyperechogenic kidneys.

Hyperechogenic kidneys are a relatively rare antenatal finding, which can generate significant parental anxiety due to uncertain prognosis. We report on the perinatal and infant outcomes of a large cohort of fetuses with antenatally diagnosed hyperechogenic kidneys. This was a retrospective analysis of all cases diagnosed prenatally with hyperechogenic kidneys between 2002 and 2017 in a large tertiary fetal medicine unit. Hyperechogenicity was defined as kidney parenchyma with greater echogenicity than that of the liver. Pregnancy, pathological and postnatal outcomes were collected from hospital and general practitioner records up to 1 year of age. Abnormal renal outcome was defined as elevated creatinine beyond 6 months of age, hypertension requiring medication or major kidney surgery, such as nephrectomy. Severe abnormal renal outcome was defined as the need for dialysis or kidney transplant at any stage. Three-hundred and sixteen fetuses with hyperechogenic kidneys were identified at a mean gestational age of 21 (range, 13-37) weeks. The majority of cases (97%) had bilateral hyperechogenic kidneys. In the 265 cases with available follow-up data, other associated renal tract abnormalities were identified prenatally in 36%, concomitant extrarenal structural abnormalities in 39% and abnormal karyotype in 15% of cases. Of the 316 included cases, 139 did not survive, including 105 terminations of pregnancy, five intrauterine deaths and 29 early neonatal deaths. Only 4.3% (6/139) of these fetuses had isolated hyperechogenic kidneys while 28.1% (39/139) had associated multiple renal tract abnormalities alongside hyperechogenic kidneys and over two-thirds (67.6%; 94/139) had concomitant extrarenal abnormalities. Of the 177 cases that survived beyond 1 month of age, outcome data were available in 126. Of these, based on the antenatal findings, 60 (47.6%) cases had isolated hyperechogenic kidneys, 56 (44.4%) had associated renal structural abnormalities and 10 (7.9%) had additional extrarenal abnormalities. Considering renal outcome alone, kidney function was abnormal in 13 (21.7%), 10 (17.9%) and 0 (0%) infants in these three groups, respectively, although concurrent pathology clearly affected global outcome in the more complex cases. Neonatal mortality of 1.6% was observed in the isolated renal hyperechogenicity group. The presence of oligohydramnios or abnormal renal volume was not associated significantly with abnormal renal function (odds ratio (OR), 2.32 (99% CI, 0.54-10.02) and OR, 0.74 (99% CI, 0.21-2.59), respectively) in this group. Hyperechogenic kidneys are often complicated by associated renal tract and extrarenal abnormalities, aberrant karyotype and genetic disease, and these factors have a greater effect on overall outcome than does kidney echogenicity. The renal outcome of fetuses with isolated hyperechogenic kidneys is good generally, with over 70% of cases having normal renal function postpartum. Importantly, for prognostic counseling, all of the fetuses in this non-selected series with isolated hyperechogenic kidneys and normal amniotic fluid levels had normal renal outcome in infancy. © 2020 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology.

MO468NEW URINARY BIOMARKERS DETECT SUBCLINICAL RENAL DAMAGE AFTER SEVERAL ACUTE KIDNEY INJURY EPISODES

Abstract Background and Aims Acute kidney injury (AKI) represents a clinical problem due to its increasing prevalence and association with further morbidities. Observational studies have shown that AKI increases the risk of a new AKI episode, chronic kidney disease (CKD), CKD progression, end-stage renal disease (ESRD), and mortality. Serum creatinine (sCr) is the parameter most used by clinicians for determining AKI and the subsequent recovery, however its use presents several limitations. sCr lacks sensitivity for AKI and provides minimal insight into the renal structure. Indeed, increases in sCr are observed only when glomerular filtration rate decreases more than 50%. Therefore, new markers need to be identified to predict recovery after AKI and to detect residual structural alterations that can cause progression to CKD. We hypothesised that after AKI, there are renal structural abnormalities that cannot be detected by common clinical parameters but may be detected by urinary biomarkers. Method We used 4 weeks old male Wistar rats. Animals were divided into 5 experimental groups: Control group: SHAM operated rats, saline solution i.p.; “CDDP5-SHAM” group: 5 mg/kg cisplatin i.p.; “Ctrl-I/R60” group: 60-minute renal ischemia reperfusion in the left kidney; “CDDP5-I/R60” group: 5 mg/kg cisplatin i.p. and after renal function normalization, 60-minute ischemia-reperfusion (I/R60); “5/6 NEF” group: 5/6 nephrectomy. Blood and urine were collected at: day 0 (basal); day 4 (AKI development); day 8 (normalized renal function after AKI and induction of renal ischemia); day 9 (1 day after ischemia); day 13, day 20 and every week thereafter. Renal function was analyzed by sCr, creatinine clearance, blood urea nitrogen and proteinuria determination using colorimetric methods. Urinary biomarkers were analyzed at day 20 (12 days after the second damage and 20 after the first one) by western blot and ELISA. Animals were sacrificed at the same time point in which urinary biomarkers were determined, and renal tissue samples were stained with Masson´s trichrome, Sirius Red and Periodic Acid-Schiff for histological analysis. Results Frequency of AKI episodes is related to the amount and degree of subclinical alterations detected in the kidneys, even though renal filtration is apparently normal. We characterized a novel panel of urinary biomarkers (bk1-bk4) several days after the last insult (day 20) when renal function appeared normal; these biomarkers were present in highest concentrations in the CDDP5-I/R60 experimental group. Conclusion These results demonstrate the importance of the clinical implementation of biomarkers as useful tools for medical support and underline the limitations of the clinical parameters (e.g. sCr, estimated GFR) currently used for renal function assessment. The frequency of AKI episodes is related to a poor prognosis, so a follow up is necessary after AKI episodes in order to prevent mortality and progression of the disease.

Peri-renal adipose inflammation contributes to renal dysfunction in a non-obese prediabetic rat model: Role of anti-diabetic drugs

Diabetic nephropathy is a major health challenge with considerable economic burden and significant impact on patients’ quality of life. Despite recent advances in diabetic patient care, current clinical practice guidelines fall short of halting the progression of diabetic nephropathy to end-stage renal disease. Moreover, prior literature reported manifestations of renal dysfunction in early stages of metabolic impairment prior to the development of hyperglycemia indicating the involvement of alternative pathological mechanisms apart from those typically triggered by high blood glucose. Here, we extend our prior research work implicating localized inflammation in specific adipose depots in initiating cardiovascular dysfunction in early stages of metabolic impairment. Non-obese prediabetic rats showed elevated glomerular filtration rates and mild proteinuria in absence of hyperglycemia, hypertension, and signs of systemic inflammation. Isolated perfused kidneys from these rats showed impaired renovascular endothelial feedback in response to vasopressors and increased flow. While endothelium dependent dilation remained functional, renovascular relaxation in prediabetic rats was not mediated by nitric oxide and prostaglandins as in control tissues, but rather an upregulation of the function of epoxy eicosatrienoic acids was observed. This was coupled with signs of peri-renal adipose tissue (PRAT) inflammation and renal structural damage. A two-week treatment with non-hypoglycemic doses of metformin or pioglitazone, shown previously to ameliorate adipose inflammation, not only reversed PRAT inflammation in prediabetic rats, but also reversed the observed functional, renovascular, and structural renal abnormalities. The present results suggest that peri-renal adipose inflammation triggers renal dysfunction early in the course of metabolic disease.

Geniposide Improves Diabetic Nephropathy by Enhancing ULK1-Mediated Autophagy and Reducing Oxidative Stress through AMPK Activation.

Diabetic nephropathy (DN) is a common pathological feature in patients with diabetes and the leading cause of end-stage renal disease. Although several pharmacological agents have been developed, the management of DN remains challenging. Geniposide, a natural compound has been reported for anti-inflammatory and anti-diabetic effects; however, its role in DN remains poorly understood. This study investigated the protective effects of geniposide on DN and its underlying mechanisms. We used a C57BL/6 mouse model of DN in combination with a high-fat diet and streptozotocin after unilateral nephrectomy and treated with geniposide by oral gavage for 5 weeks. Geniposide effectively improves DN-induced renal structural and functional abnormalities by reducing albuminuria, podocyte loss, glomerular and tubular injury, renal inflammation and interstitial fibrosis. These changes induced by geniposide were associated with an increase of AMPK activity to enhance ULK1-mediated autophagy response and a decrease of AKT activity to block oxidative stress, inflammation and fibrosis in diabetic kidney. In addition, geniposide increased the activities of PKA and GSK3β, possibly modulating AMPK and AKT pathways, efficiently improving renal dysfunction and ameliorating the progression of DN. Conclusively, geniposide enhances ULK1-mediated autophagy and reduces oxidative stress, inflammation and fibrosis, suggesting geniposide as a promising treatment for DN.

Neonatal Outcome of Antenatally Diagnosed Hydronephrosis at a Tertiary Care Centre, Telangana, India: A Prospective Study

Introduction: Antenatal Hydronephrosis (ANH) is one of the most commonly detected congenital anomaly by antenatal sonogram. It requires periodic follow-up and in selected cases, early interventions are required in postnatal period. Aim: To study the relationship between Anteroposterior Diameter (APD) of foetal renal pelvis and postnatal outcome of hydronephrosis in neonates and to study the relation between APD of foetal renal pelvis and structural abnormalities of kidney. Materials and Methods: This prospective study included neonates whose antenatal scan showed hydronephrosis. The study was conducted during the period of November 2018 to November 2020, in Niloufer Hospital (Osmania Medical College), Hyderabad, Telangana, India. A total of 50 neonates were included. For all neonates postnatal monitoring with ultrasonography was done to detect structural anomalies and resolution of hydronephrosis. Micturating cystourethrogram was done in selected cases. The cases which needed surgery were treated accordingly. The Statistical Package for the Social Sciences (SPSS) version 24.0 was used for data analysis. Kruskal-Wallis Chi-square test was used to test the significance of difference between quantitative variables. The p-value less than 0.05 was taken as statistically significant. Results: Among 50 neonates enrolled in the study, 27 (54%) had transient hydronephrosis and 23 (46%) had urogenital structural abnormalities. Twenty-two cases (44%) required micturating cystourethrogram. Antenatal APD of 9.5 mm predicted the development of significant postnatal uropathy with a sensitivity of 74% and specificity of 89%. Antenatal APD of 9.5 mm had 100% sensitivity and 67% specificity in predicting the need for surgical intervention. Only 3 (6%) cases needed surgical intervention in neonatal period and all cases were kept under follow-up. Conclusion: All cases of ANH need postnatal evaluation and pertinent follow-up to detect significant uropathy for their proper management to prevent renal damage. Antenatal renal pelvic diameter has significant role in predicting the significant uropathy and surgical intervention.

Exogenous follistatin administration ameliorates cisplatin-induced acute kidney injury through anti-inflammation and anti-apoptosis effects.

This study was aimed to explore the effects of follistatin on cisplatin-induced renal dysfunction, histopathological changes, apoptosis, inflammation and oxidative damage in rats. Follistatin plays an important role in the developmental and regeneration processes of kidney by blocking the actions of activin, which is a member of transforming growth factor-β superfamily. Twenty seven rats were separated into 4 equal groups: Control, Cp (cisplatin, 6 mg/kg, intrapertoneally (ip)), F1 (cisplatin + 1 µg/day follistatin ip for 4 consecutive days) and F4 (cisplatin + 4 µg/day follistatin ip single dose) groups. Renal health was monitored by blood urea nitrogen, serum creatinine and histological analysis. Apoptosis, inflammation and oxidative stress was investigated in kidney tissue. Activin A levels in serum and kidney were evaluated as well. Follistatin administration showed a considerable nephroprotective effect against cisplatin-induced nephrotoxicity by preventing renal functional and structural abnormalities, apoptosis and inflammation. The activin A levels in both serum and kidney were also suppressed by follistatin administration. Exogenous follistatin ameliorates acute kidney injury, by blocking activin A. The renoprotective effect of follistatin against cisplatin-induced nephrotoxicity appears to be associated with its anti-inflammatory, antiapoptotic and direct nephroprotective actions (Tab. 1, Fig. 7, Ref. 23).

Prenatal Diagnosis of Bardet-Biedl Syndrome: A Case Study and Review of Literature

AbstractBardet-Biedl syndrome (BBS) is a rare autosomal recessive disease with a prevalence rate of 1 in 125,000–170,000. BBS can occur as a result of mutation in one of the 19 known genes of the BBS gene complex. The syndrome is mostly diagnosed post-natally based on the structural and functional manifestations of the disease in childhood like short stature, obesity, polydactyly or syndactyly, retinal dystrophy, structural renal abnormalities, neurodevelopment delays, mental retardation, diabetes mellitus. We present a case of Bardet-Biedl syndrome diagnosed prenatally at 18 weeks gestation based on prenatal ultrasound findings of post axial polydactyly with bilateral hyperechogenic kidneys. Clinical suspicion based on ultrasound findings was supplemented amniocentesis and clinical exome sequencing. This showed a pathogenic variant in homozygous state in the MKKS gene, consistent with Bardet-Biedl syndrome type 6. Unless BBS has been suspected antenatally, diagnosis of BBS is usually made in late childhood or early adulthood adding to the psychological, emotional and financial burden on the family. With advances in prenatal ultrasound techniques and tremendous improvement in genetic diagnosis of suspicious findings on ultrasonography, diagnosis of rare genetic disorders like BBS is now possible as early as the 18–20 weeks scan. This can aid in appropriate counseling of the family and timely intervention in children born with this condition.

The bio-sonographic index. A novel modality for early detection of acute kidney injury after complex vascular surgery. A protocol for an exploratory prospective study.

Acute kidney injury (AKI) is a common complication of complex aortic surgery with high mortality, morbidity and health care expense. The current definition of AKI does not allow for structural characterization of the kidneys and utilizes functional indices with substantial limitations leading to delayed diagnosis and ineffective interventions. The aim of this study is to develop a method of early detection of structural renal abnormalities that can precede and predict the occurrence of AKI in this population. We propose a novel combined index of ultrasonography (shear wave elastography), biomarkers of renal stress (urinary insulin growth factor binding protein-7, IGFBP-7 and inhibitor of tissue metalloproteinase-2, TIMP-2) and renal injury markers (urinary neutrophil gelatinase-associated lipocalin -NGAL)- the bio-sonographic index (BSI). A prospective observational study at a tertiary referral center will be performed enrolling 80 patients undergoing elective open and endovascular repair of the visceral aorta. The BSI will be evaluated at baseline, and at 6 and 24 hours after the procedure. The primary outcome is the occurrence of AKI according to the Kidney Disease Improving Global Outcomes (KDIGO) criteria. Each patient will be his/her own control. A reference group of 15 healthy volunteers who are not undergoing interventions will be enrolled to test the feasibility of and to refine the novel SWE protocol. The BSI will be tested for its predictability of the occurrence of AKI. Comparisons will be made between individual and combined components of the BSI and traditional markers used in the KDIGO definition; serum creatinine and urine output in terms of baseline status of the kidney. Correlations will be made between the BSI and conventional indices of AKI and exploratory analyses will be conducted to identify individual disease patterns using the BSI. We hypothesize that the BSI will be a sensitive index of early structural abnormalities that precede and predict the occurrence of AKI as defined by KDIGO in complex vascular surgery. ClinicalTrials.gov NCT04144894. Registered 1/6/2020.

Study on the inhibitive effect of Catalpol on diabetic nephropathy

AimsCatalpol (Cat) can ameliorate oxide stress and inflammation caused by diabetic nephropathy (DN), but the molecular mechanisms are unclear. This study was designed to investigate the anti-diabetic effects of Cat and its potential mechanism. Main methodsWe constructed high-fat diet/streptozotocin (HFD/STZ)-induced DN mice and high glucose (HG)-induced podocyte model. The hypoglycemic effect of Cat was analyzed by general features of DN mice. Kidney function was detected via ELISA assay and Western blotting. Renal histopathology analysis was conducted via hematoxylin and eosin (H&E), Masson and periodic acid-silver metheramine (PASM) staining. Cellular viability was measured by TUNEL assay. In order to further study the potential mechanisms of Cat, various proteins in AMPK/SIRT1/NF-κB pathway were detected in DN mice and podocytes with siRNA-AMPK intervention using Western blotting, respectively. Key findingsWe found hyperglycemia, renal structural and function abnormalities, and increased renal inflammation in DN mice. However, Cat effectively attenuated kidney damage caused by inflammation and increased AMPK, p-AMPK and SIRT1 levels. After AMPK-siRNA transfected into HG-induced podocyte model, AMPK, p-AMPK and SIRT1 levels were obviously decreased, while Cat reversed these chandes. The levels of p-NF-κB, ASC, Cleaved IL-1β, NLRP3, Cleaved caspase1 and GSDMD-N significantly decreased by Cat treatment both in DN mice and podocyte model, which indicated that Cat could activate AMPK/SIRT1/NF-κB pathway. SignificanceCat could effectively inhibit oxide stress and inflammation accompanied with pyroptosis and its mechanism might be related to AMPK/SIRT1/NF-κB pathway, indicating that Cat possessed potential value in the treatment of DN.