Renal Abnormalities Research Articles

Exploring 17q12 Deletion Syndrome: A Case Report of Neurodevelopmental, Endocrine, and Genital Anomalies

Objective − 17q12 deletion syndrome is a rare genetic disease characterized by neurodevelopmental disorders, genital and renal abnormalities, and maturity-onset diabetes of the young type 5 (MODY5).Case Report − This case report details the case of a 13-year-old female with moderate intellectual disability, Mayer-Rokitansky-Küster-Hauser syndrome, multicystic dysplastic kidneys, and MODY5. Genetic testing revealed a 1.52-megabase heterozygous deletion on chromosome 17q12, encompassing the HNF1B and LHX1 genes, which was found to be inherited from the mother. Conclusion − This case underscores the importance of early genetic testing and multidisciplinary approach in managing the multisystemic manifestations of 17q12 deletion syndrome. Early diagnosis and appropriate management are crucial for improving the outcomes and quality of life for affected individuals.

Urinary tract infection and associated risk factors among pregnant women at a tertiary care hospital.

Objective: To determine prevalence of UTI in pregnant women and its associated risk factors at a tertiary care hospital. Study Design: Cross Sectional study. Setting: Department of Gynae & Obstetrics Independent University Hospital, Faisalabad. Period: 1-10-2022 to 31-3-2023. Methods: All pregnant patients visiting gynae OPD (5280) were enrolled for study. Mid-stream urine sample was taken and analyzed. UTI was diagnosed if >10 pus cells / HPF were seen. Inclusion Criteria: All pregnant females attending antenatal clinic during study period. Exclusion Criteria: Women with chronic renal disease. History of antibiotic treatment in last one week, Congenital renal abnormality. Patients on immuno suppressive therapy. Results: The prevalence of UTI in our study was 28%. In this study 593 patients (40%) were <20 years of age, 258(17%) were in 21-30 years age group, 246 (16%) were 31-40 years and 381(26%) were >40 years of age. In our study 526 (35%) were primigravidas, 249(17%) were G2, 272(18%) were G3 and 431 (29%) were G4 or above. In this study 698 (47%) patients were in first trimester, 320(22%) were in second trimester, 460(31%) in third trimester. Among risk factors 245 patients (16%) were anemic and 421(28%) were diabetic. Conclusion: The Prevalence of UTI in pregnant female of independent university hospital Faisalabad is quite high. Anemia and diabetes are major associated risk factors. Owing to its association with a number of complications, UTI needs to be diagnosed and treated promptly to lessen perinatal and maternal morbidity and mortality.

Evaluation of normal and abnormal fetal renal microvascular flow characteristics of three-dimensional MV-flow imaging

ObjectiveTo evaluate the applicability of three-dimensional MV-Flow imaging for prenatal renal diagnosis. MethodThis prospective study included normal and abnormal kidneys ranging from 20 to 40 weeks gestation between April and July 2023. All participants underwent conventional ultrasound and three-dimensional MV-Flow examinations. The renal volume and microvascular indexes were obtained by the three-dimensional MV-Flow. ResultsA total of 207 normal kidneys from 154 fetuses and 67 abnormal kidneys from 53 fetuses, with conditions such as renal cystic diseases, hyperechoic kidney, large kidney, and small kidney were included. Normal renal volume, vascularization index, and vascularization-flow index increased slightly with gestational age (p < 0.001). No correlation was found between gestational age and flow index (p = 0.604). The microvascular indexes decreased in the fetal renal cystic disease group while renal volume increased. Higher vascularization index and vascularization-flow index were observed in the hyperechoic kidney group. The microvascular indexes of the large and small kidney groups were within the reference range for normal kidneys. Only the autosomal dominant polycystic kidney disease exhibited an absence of distinct subcapsular microvascular flow in the MV-Flow image, referred to as the “thick shell sign”. ConclusionFetal renal volume, vascularization index, and vascularization-flow index increase with gestational age. Quantitative evaluation using 3D MV-Flow imaging reveals varying renal volume and microvascular perfusion characteristics among different fetal renal abnormalities.

Renal Inflammation, Oxidative Stress, and Metabolic Abnormalities During the Initial Stages of Hypertension in Spontaneously Hypertensive Rats.

Background: Hypertension is a major cause of mortality worldwide. The kidneys play a crucial role in regulating blood pressure and fluid volume. The relationship between the kidneys and hypertension is complex, involving factors such as the renin-angiotensin system, oxidative stress, and inflammation. This study aims to assess the levels of inflammatory markers, oxidative stress, and metabolic factors in the kidneys, focusing on their potential role in early renal damage and their association with the development of hypertension. Methods: This study was designed to compare the levels of selected inflammatory markers, e.g., interleukins, tumor necrosis factor-α (TNF-α), transforming growth factor, and serine/threonine-protein (mTOR); oxidative stress markers such as malondialdehyde, sulfhydryl group, and glucose (GLC); and metabolic markers among other enzymes, such as alanine transaminase (ALT), aspartate transaminase (AST), hexokinase II (HK-II), and hypoxia-inducible factor-1α (HIF-1α), as well as creatinine in the kidneys of spontaneously hypertensive rats (SHR/NCrl, n = 12) and Wistar Kyoto rats (WKY/NCrl, n = 12). Both juvenile (5 weeks old) and maturing (10 weeks old) specimens were examined using spectrophotometric methods, e.g., ELISA. Results: Juvenile SHRs exhibited reduced renal levels of all studied cytokines and chemokines, with lower oxidative stress and deficits in the mTOR and HK-II levels compared to the age-matched WKYs. Maturing SHRs showed increased renal levels of interleukin-1β (IL-1β), IL-6, IL-18, and TNF-α, alongside elevated carbonyl stress and increased HIF-1α as opposed to their control peers. The levels of all other studied markers were normalized in these animals, except for ALT (increased), ALP, and GLC (both reduced). Conclusions: This study underscores the significant impact of inflammatory, oxidative stress, and metabolic marker changes on renal function. Juvenile SHRs display lower marker levels, indicating an immature immune response and potential subclinical kidney damage that may contribute to hypertension development. In contrast, mature SHRs exhibit chronic inflammation, oxidative dysregulation, and metabolic disturbances, suggesting cellular damage. These changes create a feedback loop that worsens kidney function and accelerates hypertension progression, highlighting the kidneys' crucial role in both initiating and exacerbating this condition.

Effect of Sugammadex on Postoperative Pulmonary Complications and Rapid Recovery in Lung Cancer Patients Treated with Video-Assisted Thoracic Surgery: A Retrospective Cohort Study.

This study aimed to investigate the effects of sugammadex on postoperative pulmonary complications and rapid recovery in lung cancer patients undergoing video-assisted thoracic surgery (VATS). A retrospective analysis was conducted on the clinical data of 1131 lung cancer patients. Of these, 631 patients received sugammadex at the end of anesthesia, while 500 patients did not. To mitigate potential confounding factors, propensity score matching (PSM) was employed at a 1:1 ratio. After matching, 435 patients were obtained from each group. Patients who received sugammadex at the end of anesthesia were classified into Group S (n = 435) and those who did not receive sugammadex were Group P (n = 435). Postoperative pulmonary complications, indicators of recovery after surgery, nausea and vomiting, pain and lung infection scores and biochemical indices were compared between the two groups. Compared to Group P, Group S demonstrated statistically significant improvements across multiple perioperative and postoperative outcomes. Group S exhibited a lower incidence of postoperative pulmonary complications (χ2 = 9.52, p = 0.002), as well as reduced durations for several key time intervals: from the cessation of muscle relaxation to extubation (Z = 12.96, p < 0.001), from the conclusion of surgery to extubation (Z = 13.66, p < 0.001), and total operating theatre occupancy (Z = 5.81, p < 0.001). Furthermore, Group S showed accelerated recovery in terms of time to first oral intake (drink: Z = 3.80, p < 0.001; eat: Z = 3.80, p < 0.001), time to defecate (Z = 3.25, p = 0.001), and time to chest tube removal (Z = 5.04, p < 0.001). Pain management outcomes were also superior in Group S, with lower motor visual analogue scale (VAS) scores at both 24 h (Z = 4.71, p < 0.001) and 48 h (Z = 5.05, p < 0.001) postoperatively. Group S additionally demonstrated a lower modified Clinical Pulmonary Infection Score (mCPIS) (Z = 4.68, p < 0.001), reduced complication rates during the general anesthesia awakening period (χ2 = 23.54, p < 0.001), and a lower incidence of renal function abnormalities (χ2 =12.65, p < 0.001). Certain parameters, including total hospital stay duration and postoperative drainage volume, did not differ significantly between the two groups (p > 0.05). Sugammadex can effectively reduce the incidence of postoperative pulmonary complications in lung cancer patients treated with VATS, and help promote their rapid postoperative recovery with significant clinical benefits.

Insights into the Novel Biomarkers Expressed in Diabetic Nephropathy: Potential Clinical Applications.

Diabetic nephropathy (DN) is increasing worldwide in parallel with type 2 diabetes mellitus. Identifying diagnostic biomarkers for DN at an early stage is crucial due to the considerable societal and economic burden associated with diabetes mellitus (DM) and its risk factors. In the past, early indicators of microvascular problems, such as microalbuminuria (MA), have been used to predict the possibility of developing advanced chronic kidney disease (CKD). However, because of the incapacity of MA to appropriately estimate DN, particularly, non-albuminuric DN, additional markers have been suggested for recognizing the early renal abnormalities and structural lesions, even before MA. This study aims to assess the existing and future biomarkers used to diagnose or predict early DN. This review provides comprehensive insight into diagnostic approaches for early detection of CKD, addressing the following areas: (i) markers of glomerular damage, (ii) markers of tubular damage, (iii) oxidative stress biomarkers, (iv) inflammatory biomarkers and (v) futuristic biomarkers such as micro-ribonucleic acids (miRNAs), proteomics, metabolomics and genomics and gut microbiota. Early detection of DN may lead to improvement in clinical management and quality of life, emphasizing the importance of identifying a specific and reliable predictive biomarker. Emerging serum and urinary biomarkers offer promise for early DN diagnosis, potentially reducing prevalence and preventing progression to end-stage renal disease (ESRD). Further advancements in miRNAs, proteomics, metabolomics genomics and gut microbiota offer prospects for even earlier and more precise DN diagnosis.

12599 Early Remission Of Chromosome 6 Q 24-related Neonatal Diabetes Mellitus

Abstract Disclosure: R. Pratibha: None. K. Dummula: None. Introduction: Chromosome 6q24 imprinting abnormalities represent the predominant cause of transient neonatal diabetes mellitus (TNDM), accounting for over two-thirds of cases with an estimated prevalence of 1 in 400,000. While remission typically manifests by 3 months of age, herein we detail a case of Chromosome 6q24-related TNDM exhibiting remission by 1.5 months of age. We share our clinical experience in managing this case without hypoglycemia and using C-Peptide levels as a monitoring tool to track the resolution. Case: A female infant, born at 36 weeks via elective C-section due to fetal growth restriction and oligohydramnios, was closely monitored in the nursery for potential hypoglycemia. Contrary to the expectation, she displayed escalating hyperglycemia, necessitating insulin infusion within 25 hours of birth. Apgar scores were 7 and 9, and the birth weight was 2095 g (6th percentile). Maternal history included impaired glucose tolerance in a previous pregnancy with borderline glucose tolerance during this gestation. The newborn physical exam was unremarkable except for mild macroglossia. Despite initial blood glucose (BG) of 52 mg/dl, it rose to 257 mg/dL by 16 hours. Insulin drip was started at 24 hours due to BG of 304 mg/dL. The monogenic diabetes panel obtained on day of life (DOL) #2 was negative; no acidosis was observed. The C- Peptide was low at 0.2 ng/ml. Insulin infusion was continued until DOL # 20. A trial of glyburide commenced on DOL #9 while on Insulin drip, yielded minimal response, prompting a transition to short-acting insulin for correction of hyperglycemia (&amp;gt;250 mg/dL). C-peptide level during sulfonylurea (SU) trial remained low (0.5 ng/mL). The infant required 2 to 3 corrections per day with 0.05 units of Lispro Insulin, with the last dose administered at 44 days. She did not receive any long-acting Insulin. As of her last follow-up at the endocrine clinic at 57 days of age, the infant is thriving well and has normal blood glucose levels. The 6q24 Methylation-MLPA study showed duplication of 6q24 on the paternally inherited chromosome 6. Significantly, she never encountered hypoglycemia during her hospital stay. The C-peptide increased to 0.8 ng/ml at DOL#37 and had normalized to 1.3 ng/mL by DOL#57 indicating remission of TNDM. Conclusion: 6q24-related TNDM may often be characterized by features such as small for gestational age (SGA), macroglossia, umbilical hernia, cardiac and renal abnormalities. Early presentation of hyperglycemia with this phenotype must prompt its diagnostic evaluation. Early resolution by 1.5 months as seen in our case is uncommon. Uniquely, we used C-peptide as a tracking tool to guide resolution and manage insulin therapy. Presentation: 6/3/2024

Complement-mediated hemolytic uremic syndrome associated with postpartum hemorrhage: case series and systematic review of individual participant data

BackgroundPostpartum hemorrhage is considered a risk factor for pregnancy-associated complement-mediated hemolytic uremic syndrome (CM-HUS; previously known as atypical hemolytic uremic syndrome) but has not been systematically studied. MethodsA systematic review of individual participant data from case series and reports in addition to a case series from our institution. Search terms were “thrombotic microangiopathy,” “atypical hemolytic uremic syndrome,” and “complement mediated” combined with “pregnancy,” “postpartum,” and/or postpartum hemorrhage. Cases of thrombotic microangiopathy other than CM-HUS were excluded. Outcomes were clinical and laboratory characteristics of postpartum hemorrhage-associated CM-HUS, treatment, and outcomes. ResultsThirty-three studies including 48 women with postpartum hemorrhage-associated CM-HUS and 3 patients from our institution were included in the study. Most women presented at term (28/45; 62%), delivered by cesarean section (21/41; 51%), and had pregnancy complications, mainly preeclampsia (16/51; 31%) or fetal demise (/51; 18%). Hematological and renal abnormalities usually appeared within the first 24 hours postdelivery. The median platelet count was 46 × 109/L (IQR, 45), and the median maximal lactate dehydrogenase was 2638 U/L (IQR, 1866). Renal function normalized in 20/23 (87%) women treated with C5 inhibitors with or without plasma exchange; in 7/11 (63%) women treated with plasma exchange alone, but only in 3/17 (18%) patients treated with supportive care. Patients treated with C5 inhibitors and/or plasma exchange achieved significantly better renal outcomes compared with supportive care alone (P < .001). ConclusionCM-HUS is a rare complication following postpartum hemorrhage and occurs mainly in women with preeclampsia and/or following cesarean section. Patients treated with C5 inhibitors and/or plasma exchange had a better renal prognosis compared with patients who received supportive treatment alone.

Diagnosis of renal tumors in Birt-Hogg-Dube syndrome: Clinical presentation and risk factors in a single-center retrospective cohort

BackgroundBirt-Hogg-Dube (BHD) syndrome is a rare genetic condition associated with the development of renal tumors. This study aims to determine typical age ranges for detecting renal abnormalities, risk factors for tumor development, and long-term outcomes based on current surveillance strategies.MethodsA single-center multi-site retrospective cohort study was performed on all patients with BHD diagnosed from 2000 to 2023. Baseline demographics, pulmonary function, laboratory, radiologic, and histopathologic findings were collected. Logistic regression was used to assess predictor variables for the development of renal tumors with survival analysis evaluated from the date of BHD diagnosis to date of death or last known follow-up.ResultsThe study included 149 patients with BHD, 39 (26%) with diagnosed renal tumors, of which 28 had histopathologic confirmation. Mean age at renal tumor detection was 53.61 years. Older age and male sex were predictive of renal tumor development ((odds ratio 1.05; 95% CI, 1.01–1.08, P = 0.002) and (odds ratio 2.59; 95% CI, 1.17–5.73, P = 0.02), respectively). Time to all-cause mortality appeared shorter in those with renal tumors (Log-rank P = 0.02), though no deaths were from cancer or cancer-related complications.ConclusionsCurrent screening protocols for renal tumors in BHD suggest the most common presenting age range for presentation is late 40s to early 50s, with older age and male sex as risk factors for tumor development.

External ear malformations and cardiac and renal anomalies: A systematic review and meta-analysis.

External Ear Malformations (EEM) continue to be a common malformation seen in the pediatric patient population. This study aims to further elucidate the correlation between EEM and cardiac and renal anomalies. A systematic review and meta-analysis to study the incidence of cardiac and renal anomalies associated with syndromic and isolated (EEM). The literature search spanned multiple databases, including Google Scholar, PubMed, Scopus, Web of Science, and MEDLINE. Studies must be focused on EEM and cardiac and/or renal anomalies. Only articles written in English were included. General study characteristics, number of EEM patients, number of cardiac and renal anomalies and whether cases were syndromic were extracted from the studies. Of 1,058 initial studies, 33 were included for meta-analyses. Mean JBI score for all included studies was 92.06%, indicating acceptable study quality. Interrater reliability was high, with a Cohen kappa score for all studies of 0.94. The resulting pooled prevalence of cardiac abnormalities was 20% [95% CI:13-28%], while renal abnormalities were 13% [95% CI: 7-20%]. The most common anomalies were VSD (3.725%) and renal agenesis (2.04%). The presence of syndrome data across studies was not a significant modifier of prevalence rates. Primary limitation is due to heterogeneity in individual study methodology and reporting standards. These results highlight a higher prevalence of cardiac-related conditions than renal anomalies in patients with both syndromic and non-syndromic EEM in the included studies, underscoring the need for thorough clinical evaluations.

Molecular cytogenetic characterization of isolated recurrent 4q35.2 microduplication in Chinese population: a seven-year single-center retrospective study

BackgroundWith the extensive use of chromosomal microarray analysis (CMA), an increasing number of variants of uncertain significance (VOUS) have been detected. The objective of the present study was to elucidate the pathogenicity and clinical variability associated with isolated recurrent 4q35.2 microduplications within the Chinese population.MethodsThe present study involved 14 cases of isolated recurrent 4q35.2 microduplication (including 12 fetuses and 2 cases of pediatric patients) out of 5,188 subjects who sought genetic consultation at our hospital and received CMA detection. WES technology was subsequently utilized to identify additional sequence variants in a patient with multiple clinical anomalies.ResultsAll 14 cases exhibited isolated recurrent 4q35.2 microduplications spanning a 1.0-Mb region encompassing the ZFP42 gene. Among the 12 fetuses, 11 displayed normal clinical features, while one was born with renal duplication and hydronephrosis. Additionally, in the two pediatric patients, WES was performed for Case 1, who presented with congenital cataracts, severe intellectual disability, and seizures. This patient inherited the 4q35.2 microduplication from his phenotypically normal mother. WES identified a novel NM_000276:c.2042G > T (p.G681V) variant in the OCRL gene, which is associated with Lowe syndrome and may account for the observed phenotypic variability within this family.ConclusionA series of 14 cases with isolated recurrent 4q35.2 microduplications were investigated, highlighting a potential association with increased susceptibility to renal abnormalities. Further, the present findings may expand the mutation spectrum of the OCRL gene associated with Lowe syndrome and provide valuable insights for the genetic etiological diagnosis of patients with unexplained copy number variants.

Association of Angiotensin Converting Enzyme (insertion\deletion) and Angiotensin II Type 1 Receptor (A1166C) gene polymorphisms with diabetic nephropathy in Iraqi type 2 diabetic patients

Renin-angiotensin-aldosterone system abnormalities are the most prevalent cause of renal hemodynamic abnormalities, and candidate genes in this system are involved in the etiology of diabetic nephropathy (DN). A polymorphism in the angiotensin converting enzyme (ACE) gene I(insertion)\D(deletion) has been correlated to plasma ACE levels. Furthermore, the Angiotensin II Type 1 Receptor AGT1R (A1166C) expression pattern is highly related to nephropathy. The objectives of this study involved evaluating the frequency of the ACE (I/D) and AGT1R (A1166C) gene polymorphisms and investigating the association of these polymorphism with the development of DN in Iraqi patients with Type 2 diabetes mellitus (T2DM) and evaluating the levels of several urinary and serum markers in relation to studied polymorphisms. This is a cross-sectional study that included 161 T2DM patients whom were divided into two groups: T2DM with DN(included 98 patients) and normalbuminuric T2DM (included 63 patients). ACE gene polymorphism analysis revealed that the D allele was far more prevalent in DN patients compared to normalbuminuric patients (60.2% vs. 50.8%), while the I allele frequency was 39.8% in DN and 49.2% in normoalbuminuric patients. In addition, DN patients carrying the DD genotype had higher serum kidney injury molecule 1 (KIM1), serum cystatin C (CysC), and HbA1C and lower glomerular filtration rate (GFR) compared to ID+II genotypes. For AGT1R (A1166C), both DN and normalbuminuric patients had a comparable high prevalence of the AA genotype, followed by the AC genotype, while the CC genotype had been seen only in 3 patients. In conclusion, among the studied T2DM patients, individuals with DD genotype had higher frequency of DN and had 2-fold risk for DN compared to II genotype which had the lowest risk for DN. Also the current study shows that the A1166C polymorphisms of AGT1R distribution frequency were similar for both study groups with higher frequency for A allele compared to C allele and not associated with risk of DN in Iraqi T2DM Keywords: Angiotensin Converting Enzyme (I\D) gene polymorphism, Angiotensin II Type 1 Receptor (A166C) gene polymorphisms, Cystatin C, Diabetic nephropathy, Kidney injury molecule1.

Genetic analysis of a Chinese pedigree affected with Branchio-oculo-facial syndrome and a literature review

To explore the genetic etiology of a Chinese pedigree affected with Branchio-oculo-facial syndrome (BOFS) and summarize the prenatal phenotype of BOFS patients. A pedigree with BOFS which had presented at the Genetics and Prenatal Diagnosis Center of the First Affiliated Hospital of Zhengzhou University in December 2021 was selected as the study subject. Clinical data of the pedigree was collected. The fetus was subjected to routine prenatal ultrasound scan. Trio-whole exome sequencing (trio-WES) was carried out for the fetus and its parents, and candidate variant was verified by Sanger sequencing. Relevant literature was searched from the database to summarize the prenatal phenotype of BOFS patients. Ultrasound exam suggested the fetus had cleft lip and palate. Its father had presented with high palatal arch, prematurely grayed hair, occult cleft lip, congenital preauricular fistula, red-green color blindness and unilateral renal agenesis. Its grandfather also had high palatal arch, prematurely gray hair, protruding ears, congenital preauricular fistula and hearing disorders. Trio-WES revealed that the fetus and its father had both harbored a heterozygous c.890-1G>A variant of the TFAP2A gene. The same variant was not found in its mother. Sanger sequencing confirmed that its grandfather had also harbored the same variant. Based on the guidelines from the American College of Medical Genetics and Genomics (ACMG), the variant was rated as likely pathogenic (PVS1+PM2_Supporting). Combined with 36 similar cases retrieved from the literature, the prenatal phenotypes of BOFS patients had included growth restriction (25/37), renal abnormalities (10/37), cleft lip and palate (5/37) and oligohydramnios (5/37). The c.890-1G>A variant of the TFAP2A gene probably underlay the pathogenesis of BOFS in this pedigree. Discovery of the novel variant has enriched the mutational spectrum of the TFAP2A gene. The common prenatal phenotypes of BOFS have included growth restriction, renal abnormalities, cleft lip and palate and oligohydramnios. Delineation of the intrauterine phenotype of BOFS may facilitate its prenatal diagnosis, clinical diagnosis, treatment and genetic counseling.

Effect of Presence of Uni- or Bilateral Thyroid Adenoma on Recovery of Pituitary-Thyroid Axis and Creatinine Concentration in Radioiodine-Treated Cats.

Radioiodine therapy (RAIT) is the gold standard for treatment of hyperthyroidism in cats. The aim of this study was to evaluate the effect of the presence of uni- or bilateral thyroid adenoma on changes in total thyroxine (TT4), thyroid-stimulating hormone (TSH), and creatinine concentration over a period of 6 to 12 months following RAIT. Fifty-one hyperthyroid cats presented for RAIT between April 2021 and April 2022 were prospectively enrolled. Cats with an increased creatinine concentration (creatinine ≥ 140 µmol/L), renal morphology abnormalities, and suspected thyroid carcinoma were excluded. TT4, TSH, and creatinine were determined before and one week and one, three, six, and twelve months following RAIT. The effects of the re-examination timepoint following RAIT and the presence of uni- or bilateral thyroid adenoma based on technetium-99m scintigraphy on TT4, TSH, and creatinine were analysed by mixed effects modelling. Cats with bilateral adenoma had significantly higher TSH concentrations after RAIT compared to those with unilateral adenoma. TT4 concentration significantly decreased one week (p < 0.001) and again one month following RAIT (p < 0.001). TSH and creatinine concentration significantly increased one month post RAIT (both p < 0.001). As indicated by an increase in TSH concentration, the pituitary-thyroid axis needs a minimum of one month post RAIT to recover from hyperthyroidism-induced suppression, but hypothyroidism necessitating levothyroxine supplementation might not be diagnosed before 6 or even 12 months post RAIT. Although creatinine did not increase significantly after one month post RAIT in this cohort, an increased creatinine concentration was detected at later timepoints in individual cats.

Clinical Profile and Outcomes of Patients With Systemic Lupus Erythematosus.

Background Systemic lupus erythematosus (SLE) is a complex autoimmune disorder characterized by relapsing-remitting immune system activation, affecting multiple organ systems. Despite significant advances in understanding SLE's pathogenesis, there remains a need for comprehensive clinical profiling at the time of diagnosis to improve early detection and management. This study addresses this gap by providing a detailed analysis of the clinical presentation, disease activity, and patient outcomes using the Systemic Lupus International Collaborating Clinics (SLICC) criteria and Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) index. Methodology This cross-sectional observational study included 80 patients diagnosed with SLEusing the 2012 SLICC criteria. Patients were recruited from the Rheumatology department and other wards of Byramjee JeejeebhoyGovernment Medical Collegeand Sassoon General Hospital, Pune, India. All participants provided informed consent and institutional ethical approval was obtained. Data were collected through detailed clinical history, physical examinations, and standard tests such aschest X-rays, CBC, RFT, LFT, urine microscopy, creatine phosphokinase, ANA, AntiDsDNA, complement consumption, and Coombs' tests, with 2D echocardiography performed as needed. Follow-ups every three months over 1.5 years assessed disease activity using SLEDAI criteria. Patients aged 12 and above who met the SLICC criteria were included and those with other connective tissue disorders were excluded. Associations between clinical symptoms and organ involvement were analyzed using thechi-square testwith a p-value of <0.05 considered significant. Results The study evaluated 80 patients with SLE, revealing a predominantly female cohort (80%) with a mean age of 29.4 years and a standard deviation of 8.3 years, skewed towards younger age groups. Clinical manifestations were diverse; the most common symptoms were (83.75%), oral ulcers (98.75%), and alopecia (95%). Anemia (66.25%) was the most prevalent abnormality, followed by albuminuria and renal abnormalities. Organ involvement was highest in the renal system (50%) and mucocutaneous features, with lower incidences in cardiac, gastrointestinal, and vascular systems. Gender-specific analyses indicated significant differences in SLE nephritis (p=0.048) and autoimmune hemolytic anemia (p=0.046). Autoantibody profiles showed high positivity for ANA (98.8%) and DsDNA (61.3%). Clinical outcomes demonstrated that 68.8% of patients achieved remission and 16.3% experienced organ damage. The SLEDAI scores significantly improved over time, with substantial reductions from baseline to nine months (p<0.001). Conclusion In conclusion, this study provides a detailed examination of SLE, revealing that it predominantly affects young adults and is characterized by diverse manifestations including mucocutaneous symptoms, significant renal involvement, and notable autoantibody profiles. The high prevalence of anti-nucleosome and anti-dsDNA antibodies underscores their diagnostic and prognostic value. Clinically, the findings highlight the necessity for early detection and targeted management of SLE, particularly in addressing renal and mucocutaneous symptoms. Future research should focus on longitudinal studies to track disease progression, explore genetic and environmental influences, and investigate regional variations to enhance treatment strategies and patient outcomes.

Clonal monocytosis of renal significance

Clonal monocytosis reflects a preneoplastic or neoplastic sustained increase in the absolute monocyte count in the absence of reactive causes. Causes of clonal monocytosis include clonal cytopenias with monocytosis and acute and chronic myeloid neoplasms. Chronic myelomonocytic leukemia is a prototypical myelodysplastic/myeloproliferative overlap neoplasm in adults, characterized by sustained peripheral blood monocytosis. Renal abnormalities, including acute kidney injury and chronic kidney disease, are frequent in patients with chronic myelomonocytic leukemia and are predictors of worse outcomes. In addition, acute kidney injury/chronic kidney disease often limits eligibility for allogeneic stem cell transplantation or enrollment in clinical trials. In this review, we highlight clonal monocytosis-related etiologies that give rise to acute kidney injury and chronic kidney disease, with special emphasis on chronic myelomonocytic leukemia and lysozyme-induced nephropathy. Monocytes produce lysozyme, which, in excess, can accumulate in and damage the proximal renal tubular epithelium. Early identification of this etiology and a timely reduction in monocyte counts can salvage renal function. Other etiologies of renal injury associated with clonal monocytosis include direct renal infiltration by monocytes, renal extramedullary hematopoiesis, myeloproliferative neoplasm-associated glomerulopathy, autoimmune (membranous nephropathy, minimal change disease) and paraneoplastic manifestations, thrombotic microangiopathy, obstructive nephropathy due to myeloproliferation, and urate nephropathy due to tumor lysis syndrome. We propose to group these mechanistic etiologies of renal injury as clonal monocytosis of renal significance and provide guidance on their diagnosis and management.

O39 IMPACT OF UROMODULIN CONCENTRATION ON RENAL AND HAEMODYNAMIC PARAMETERS IN A BLACK AFRICAN COMMUNITY WITH A HIGH PREVALENCE OF HYPERTENSION

Background and Objective: The burden of hypertension (HTN) and related comorbidities disproportionately affects developing countries like South Africa, particularly in urban populations of African ancestry. This demographic exhibits a volume-dependent form of HTN that is resistant to antihypertensive drugs that target the renin-angiotensin-aldosterone system. Renal fluid retention or abnormalities may cause HTN in this group, thus the need to investigate various nephron components for a better understanding. Uromodulin is a potential biomarker for renal function and tubular reserve. However, the relationship with renal function, haemodynamic parameters and HTN in a Black African population is unknown. Therefore, the aim of this study was to explore the relationship between urinary uromodulin concentration and renal as well as haemodynamic parameters in a Black African community with a high prevalence of volume-dependent HTN. Methods: Systemic haemodynamics (central pressures [SphygmoCor] and echocardiographic aortic velocity and diameter measurements in the outflow tract), urinary uromodulin concentrations (ELISA assay) and renal function (creatinine clearance from 24-hour urine collections [n=370]) were determined in a Black African community (n=397). Results: No relationships between urinary uromodulin concentrations and age, body mass index, blood pressure or hypertension were noted. However, urinary uromodulin concentrations were higher in females than males, even after adjusting for several confounders (p=0.0007). Although urinary uromodulin concentrations were unrelated to renal function, an inverse relationship with stroke volume (SV) was observed (p=0.0023). The inverse relationship between SV and urinary uromodulin concentration was independent of confounders and present in hypertensives (p=0.007) but not normotensives (p=0.43). The hypertensives were noted to have a higher SV than the normotensives (p=0.047). Conclusion: In a Black African community sample with a high prevalence of volume-dependent primary hypertension, urinary uromodulin was inversely related to SV, particularly in participants with hypertension. These data suggest the need to investigate the mechanisms linking urinary uromodulin to haemodynamic parameters to identify novel pathways to target for better treatment strategies in hypertension.

Abstract P118: Effect of renal denervation on the blood pressure and progression of diabetic kidney disease in T2DN rats

Background: As a common complication of diabetes, diabetic kidney disease (DKD) is a chronic progressive disorder that can lead to kidney failure, and it is currently the leading cause of kidney replacement therapy in the USA and worldwide. Although renal denervation (RDNx) has recently been approved by the FDA to treat hypertension, contradictory findings have been reported on the effect of RDNx on the blood pressure and progression of DKD in type 2 diabetic mellitus. Here, we used type 2 diabetic nephropathy (T2DN) rats, a well-established non-obese model that displays similar renal abnormalities and hyperglycemic levels as seen in humans, to evaluate the effect of RNDx on the blood pressure and progression of DKD. Methods: Bilateral RDNx or sham surgeries were performed on male T2DN rats with mild and severe stages of DN (~20 or &gt;35 weeks old). The blood pressure was monitored chronically using radio telemetry throughout the entire experiment. 24-hr urine collection, glucose tolerance test, and GFR measurement were performed at baseline and at the end of the experiments. Blood and urine electrolytes were measured using a blood gas analyzer. The amount of norepinephrine in the kidney was evaluated by ELISA. Results: Bilateral RNDx were successfully performed on T2DN rats with a significant reduction of norepinephrine in the kidneys of the RDNx group (244±13 vs. 8±1 pg/mg for &gt;35 weeks old rats). The mean arterial pressure (MAP) and heart rate remain the same between the Sham and RDNx groups. The glucose tolerance test also indicates no difference between the two groups. While there is a significant decrease in the GFR in Sham group from baseline to week 3, the GFRs between Sham and RDNx groups are not different. Similarly, total body weight, kidney to total body weight ratio, heart to total body weight ratio, and blood and urine electrolytes are also not different between Sham and RDNx groups. Analysis of the younger group (~20 weeks old) is in progress. Conclusion: In summary, our data suggests that RDNx does not affect the blood pressure and progression of DKD in male T2ND rats, at least at the stage of severe kidney injury (&gt;35 weeks old). Funding sources: National Institute of Health R01 DK135644 and R01 DK129227, Department of Veterans Affairs I01 BX004024 (to AS), and APS Postdoctoral fellowship (to BX).

Challenges in diagnosis of Erdheim-chester disease: a case report

Background: Erdheim-Chester disease is a rare non-Langerhans cell histiocytosis characterized by the infiltration of lipid-laden macrophages into various tissues, leading to diverse clinical manifestations. Case Presentation: A 53-year-old male presented with a history of recurrent flank pain and obstructive uropathy over seven years, which led to multiple imaging studies and treatments for bilateral renal stones. Recent imaging, including a CT scan of the abdomen and pelvis, revealed bilateral perirenal soft tissue thickening extending into the renal sinus and pelvicalyceal systems, moderate hydronephrosis, and bilateral renal stones, suggestive of ECD. A CT-guided biopsy of the perinephric soft tissue confirmed the diagnosis. Histopathological analysis showed fibrofatty tissue with histiocytes exhibiting foamy cytoplasm, lymphocytes, plasma cells, and Touton cells. Immunohistochemistry stains were positive for Factor 13A and CD68 in histiocytes, confirming ECD. Conclusion: This case underscores the importance of considering ECD in patients with unexplained recurrent flank pain and renal abnormalities. Early recognition and biopsy are crucial for accurate diagnosis and management of this rare disease. The successful identification of ECD in this patient illustrates the critical role of advanced imaging and histopathological evaluation in diagnosing rare conditions.

Nandrolone decanoate induced kidney injury through miRNA-146a targeting IRAK1 and TRAF6 via activation of the NF-κB pathway: The effect of moderate exercise

Anabolic-androgenic steroids (AAS) abuse is linked to some abnormalities in several tissues including the kidney. However, the precise molecular mediators involved in AAS-induced kidney disorder remain elusive. The main objective of the present study was to investigate the effect of Nandrolone decanoate on kidney injury alone or in combination with moderate exercise and its related mechanisms. Thirty-two male Wistar rats were subdivided randomly into four groups. control (Con), Nandrolone (10 mg/kg)(N), Exercise (Exe), Nandrolone + Exercise (N+Exe). ResultsAfter 6 weeks, nandrolone treatment led to a significant increase in functional parameters such as serum cystatin c, urea, creatinine, albuminuria and Albumin/ creatinine ratio indicating kidney dysfunction. Moreover, nandrolone treatment increased vacuolization, focal inflammation, hemorragia, cast formation fibrosis in the renal tissue of rats. miRNA-146a increased in kidney tissue after nandrolone exposure by using RT-PCR which may be considered idealtheranomiRNAcandidates for diagnosis and treatment.Western blotting indicated that IRAK1, TRAF6, TNF-α, NF-κB, iNOS and TGF-β protein expressions were considerably elevated in the kidneys of nandrolone treated rats. Moderate exercise could alleviate the renal dysfunction, histological abnormalities and aforementioned proteins. Our findings suggested that nandrolone consumption can cause damage to kidney tissue probably through miRNA-146a targeting IRAK1 and TRAF6 via activation of the NF-κB and TGF-β pathway. These results provide future lines of research in the identification of theranoMiRNAs related to nandrolone treatment, which can be ameliorated by moderate exercise.