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Depression and osteoporosis are common diseases in dialysis patients. In addition, patients with osteoporosis are more susceptible to depression. Contrary to previous anti-osteoporosis agents, denosumab and romosozumab could be used in dialysis patients and have similar action mechanisms for blocking RANKL. RANKL causes bone resorption after binding RANKL, but binding with OPG leads to suppress of bone resorption. In recent mice study, inhibition of RANKL with denosumab improved depressive-like phenotype. Besides, it was found that OPG was associated with depression. Therefore, this study aimed to investigate the association of depressive symptoms with RANKL and OPG in hemodialysis patients. We conducted a cross-sectional study with a total of 172 hemodialysis patients. The participants were measured for plasma RANKL, OPG, MMP-2, and MMP-9 levels. Logistic regression analysis was performed to evaluate the effect of RANKL and OPG on the presence of depressive symptoms. The depressive symptoms were observed in 90 (52.3%) subjects. RANKL tertile 3 had negative association with BDI score (β − 4.527, 95% CI − 8.310 to − 0.743) in univariate analysis, and this association persisted even after multivariate adjustments (β − 5.603, 95% CI − 9.715 to −1.491) in linear regression. In logistic regression between RANKL tertiles and depressive symptoms, RANKL tertile 3 had significantly lower unadjusted OR (0.40, 95% CI 0.19–0.86), and multivariate-adjusted OR (0.31, 95% CI 0.12–0.82) for depressive symptoms. OPG was not significantly associated with depressive symptoms. Higher plasma RANKL concentrations were significantly associated with lower depressive symptoms in HD patients. Trial registration WHO registry, No. KCT0003281, date: January 12, 2017. [ABSTRACT FROM AUTHOR]

Apparent treatment‐resistant hypertension (aTRH), defined as blood pressure (BP) that remains uncontrolled despite unconfirmed concurrent treatment with three antihypertensives, is associated with an increased risk of developing cardiovascular and renal complications compared with controlled hypertension. We aimed to identify the characteristics of aTRH patients with an elevated risk of major adverse cardiovascular events plus (MACE+; defined as stroke, myocardial infarction, or heart failure hospitalization) and end stage renal disease (ESRD). This retrospective cohort study included aTRH patients (BP ≥140/90 mmHg and taking ≥3 antihypertensives) from the United States–based Optum® de‐identified Electronic Health Record dataset and used machine learning models to identify risk factors of MACE+ or ESRD. Patients had claims for ≥3 antihypertensive classes within 30 days between January 1, 2015 and June 30, 2021, and two office BP measures recorded 1–90 days apart within 30 days to 11 months after the index regimen date. Of a total 18 797 070 patients identified with any hypertension, 71 100 patients had aTRH. During the study period (mean 25.5 months), 4944 (7.0%) patients had a MACE+ and 2403 (3.4%) developed ESRD. In total, 22 risk factors were included in the MACE+ model and 16 in the ESRD model, and most were significantly associated with study outcomes. The risk factors with the largest impact on MACE+ risk were congestive heart failure, stages 4 and 5 chronic kidney disease (CKD), age ≥80 years, and living in the Southern region of the United States. The risk factors with the largest impact on ESRD risk, other than pre‐existing CKD, were anemia, congestive heart failure, and type 2 diabetes. The overall study cohort had a 5‐year predicted MACE+ risk of 13.4%; this risk was increased in those in the top 50% and 25% high‐risk groups (21.2% and 29.5%, respectively). The overall study cohort had a predicted 5‐year risk of ESRD of 6.8%, which was increased in the top 50% and 25% high‐risk groups (10.9% and 17.1%, respectively). We conclude that risk models developed in our study can reliably identify patients with aTRH at risk of MACE+ and ESRD based on information available in electronic health records; such models may be used to identify aTRH patients at high risk of adverse outcomes who may benefit from novel treatment interventions. [ABSTRACT FROM AUTHOR]

Key Clinical Message: Microscopic polyangiitis is a rare autoimmune vasculitis, that could present with renal‐pulmonary symptoms, posing diagnostic challenges in patients with preexisting kidney disease. Timely diagnosis is crucial to improve patient outcomes. [ABSTRACT FROM AUTHOR]

Introduction: COVID-19, caused by SARS-CoV-2, has resulted in significant mortality and morbidity worldwide. Patients of chronic kidney disease who are on maintenance hemodialysis represent a vulnerable population cohort that is susceptible to severe disease. Hence, it is of utmost importance to prioritize vaccination in this population and to assess their response to said vaccination. Methods: This prospective analytical study was conducted at the Institute of Nephrology, Madras Medical College, between August 2021 and February 2022. Patients of chronic kidney disease stage 5 dialysis (CKD5D) who were on maintenance hemodialysis and who consented to receive COVID-19 vaccine were studied. Serum samples were obtained before vaccination, ≥28 days after receiving the first dose of the vaccine, and ≥28 days after receiving the second dose. Antibody titers against the spike protein were estimated using the Roche chemiluminescent immunosorbent assay. Patients were grouped into non-responders/seronegative (<0.8 U/ml) and responders/seropositive (≥0.8 U/ml), with a value ≥250 U/ml considered as robust response. Results: A total of 96 patients were included. The mean age was 36.70 (±11.53) years and 77.1% of them were male. The median dialysis vintage was 2 (IQR: 0.95-5) years. Twelve patients (9.9%) had a prior COVID-19 infection. Sixty-seven (69.8%) patients had received Covaxin and 29 (30.2%) had received Covishield vaccines. Among the 17 patients who were seronegative at baseline, 4 (23.52%) became seropositive after the first dose of the vaccine, and 11 (64.7%) were seropositive after the second dose, with high titers ("robust response") achieved in two patients (11.76%). No antibody response, despite two doses of the vaccine, was noted in six patients (35.29%). Conclusion: Our study showed a high baseline seropositivity rate, even prior to vaccination, which indicated a high rate of subclinical COVID infection. Among those who were seronegative at baseline, the seroconversion rate after two doses of Covaxin or Covishield was 64.70%. [ABSTRACT FROM AUTHOR]

Objective: We sought to evaluate the left atrial (LA) strain parameters of maintenance hemodialysis (MHD) patients before and after dialysis by two dimensional speckle tracking imaging (2D‐STI), and to explore the effect of volume load change on LA function. Methods: Seventy‐six patients with end stage renal disease (ESRD) on hemodialysis (HD) were enrolled in the study protocol. The median duration of dialysis was 24.0 (7.5, 59.5) months. In addition, 30 healthy subjects were selected as control group. Comprehensive echocardiography was performed immediately before and after hemodialysis to compare the changes in left atrial function. Results: Regarding LA strain parameters in patients of pre‐HD, the median (25th, 75th) LA reservoir, LA conduit, and LA contractile reserve were 28.0 (23.0, 34.5), −15.5 (−10.0, −21.5), −12.0 (−9.0, −16.0) respectively; the post‐HD were 26.0 (21.0, 29.0), −12.0 (−9, −15.5), −12.5 (−9, −15.5) respectively; and controls were 43.0 (36.0, 48.0), −24.0 (−18.0, −32.0), −17.0 (−15.0, −22.0) respectively. The left atrial strain parameters before HD were lower than controls, the differences were statistically significant, the p‐value were.000,.025, and.000, respectively. The reservoir function and conduit function of LA strain decreased after hemodialysis, the differences were statistically significant, the p‐value were.003 and.006, respectively. Regarding the contraction of LA, the differences between pre‐ and post‐HD were not statistically significant (p =.965). Conclusion: Hemodialysis removes excess water in human body, while LVGLS and Doppler parameters are greatly affected by reduced preload. New echocardiographic parameters, such as left atrial strain, can quantitatively evaluate the changes in left atrial function before and after hemodialysis in ESRD patients, which can provide valuable information for the overall cardiac evaluation in this specific population. [ABSTRACT FROM AUTHOR]

Background/Aims: The aim of this study is to investigate the utility of clinical [age, gender, mean arterial pressure (MAP)] and laboratory parameters [eGFR, hemoglobin (Hgb), serum levels of creatinine, uric acid, albumin, proteinuria, hematuria] and also histopathological lesions (Oxford classification parameters, crescents, intensity and pattern of staining for C3, C1Q, IgA, IgG, IgM) as progression markers in patients with IgA Nephropathy (IgAN). Methods: A total of 111 IgAN patients with a follow-up period >1 year or who reached kidney failure [GFR category G5 chronic kidney disease (CKD)] <1 year were investigated. Primary endpoint was the development of kidney failure or eGFR decline ≥50% from the baseline. Kaplan-Meier and Cox proportional hazards analyses were performed. Results: Mean follow-up period was 33±29 months. Thirty-seven (33.3%) patients progressed to kidney failure and 4 (3.6%) patients developed eGFR decline ≥50% from the baseline after a median of 23 and 65 months, respectively. In multivariate Cox regression analysis, baseline levels of Hgb (HR:0.782, 95% CI 0.559-0.973, p=0.037), serum uric acid (HR:1.293, 95% CI 1.023-1.621, p=0.046), eGFR (HR:0.966, 95% CI 0.947-0.984, p=0.004) and intensity of C3 staining (HR:1.550, 95% CI 1.198-1.976, p=0.049) predicted primary endpoint. Serum uric acid level was associated independently with T score (β=0.303, p=0.005) in patients with eGFR>30 ml/min/m2. Conclusions: Hyperuricemia and the deposition of C3 are independent risk factors for IgAN progression. [ABSTRACT FROM AUTHOR]

Objectives: This study aimed to determine the risk factors associated with the failure of arteriovenous fistulae (AVF) maturation. Methods: This retrospective cohort study was conducted from January 2014 to December 2018 in Sultan Qaboos University Hospital, Muscat, Oman. Patients were followed-up 3 months after surgery, and their electronic medical records were accessed for demographic and clinical data. Univariate analysis was used to determine the risk factors associated with early AVF maturation and multivariant analysis was used to determine the predictive factors for AVF failure. Results: A total of 269 patients were included. Female gender was a significant factor affecting AVF maturity (P = 0.049), while age (P = 0.626), diabetes (P = 0.954), hypertension (P = 0.378), dyslipidaemia (P = 0.907), coronary artery disease (P = 0.576), cerebrovascular accident (P = 0.864), congestive heart failure (P = 0.685), previous central venous catheterisation (P = 0.05), fistula type (P = 0.863) and fistula site (P = 0.861) did not affect AVF maturation. Binary logistic regression showed that all the risk factors were insignificant. Failure of early AVF maturation affected 11.5% in the cohort. Conclusion: This study found that the proportion of early AVF maturation at our hospital is at par with that in the international literature. Failure of AVF maturation was significantly associated with the female gender. These findings can help nephrologists and vascular surgeons prognosticate AVF maturation rates. However, a larger study is needed for definitive conclusions. [ABSTRACT FROM AUTHOR]

Introduction: Ocular manifestations of Haemodialysis (HD) are one of the important causes of morbidity in End-stage Renal Disease (ESRD) patients. According to studies, the incidence rate of glaucoma in the dialysis group was higher than that in the non dialysis group. Angle-closure glaucoma was found to be more common, which depends on anterior chamber morphology. Aim: To assess the effect of HD on Intraocular Pressure (IOP), Anterior Chamber Depth (ACD), and Lens Thickness (LT) in patients with ESRD. Materials and Methods: This was a single-centre crosssectional observational study conducted in the Department of Ophthalmology on 170 eyes of 87 patients undergoing HD for at least three months. The study was conducted between October 2020 and October 2022 at the Dialysis Centre of Bharati Vidyapeeth (DTU) Medical College and Hospital, Pune, Maharashtra, India. These patients underwent ophthalmological evaluation pre- and postdialysis. IOP, ACD, and LT were measured 30 minutes prior to and 30 minutes after the HD session. The paired t-test was used to compare differences in means, and a p-value of <0.05 was considered significant. Results: The mean age of the study participants was 57.63±11.95 years. There was a decrease in mean ACD by 0.08±0.29 mm (p=0.0001) and an increase in mean LT by 0.06±0.42 mm (p-value=0.0001) postdialysis. The changes in IOP were variable and not statistically significant (p=0.45). Conclusion: Postdialysis, a significant increase in LT was observed corresponding to a decrease in ACD. Although the change in IOP was variable, this change might be more significant in pre-existing narrow-angle patients undergoing dialysis. As a result, the present study underscores the urgency of refining screening protocols for HD patients to effectively address these identified ocular changes and associated risks. [ABSTRACT FROM AUTHOR]

[Display omitted] • Metabolomics reveals potential diagnostic markers for diabetic nephropathy (DN). • Lipid metabolism in podocytes emerges as pivotal in DN. • Cinaciguat activation of NO/sGC/PKG pathway shows promise in DN. • Tryptophan levels serve as prognostic indicators for DN progression. • Integration of metabolomics enhances understanding and management of DN. Diabetic nephropathy (DN), a severe complication of diabetes, involves a range of renal abnormalities driven by metabolic derangements. Metabolomics, revealing dynamic metabolic shifts in diseases like DN and offering insights into personalized treatment strategies, emerges as a promising tool for improved diagnostics and therapies. We conducted an extensive literature review to examine how metabolomics contributes to the study of DN and the challenges associated with its implementation in clinical practice. We identified and assessed relevant studies that utilized metabolomics methods, including nuclear magnetic resonance (NMR) spectroscopy and mass spectrometry (MS) to assess their efficacy in diagnosing DN. Metabolomics unveils key pathways in DN progression, highlighting glucose metabolism, dyslipidemia, and mitochondrial dysfunction. Biomarkers like glycated albumin and free fatty acids offer insights into DN nuances, guiding potential treatments. Metabolomics detects small-molecule metabolites, revealing disease-specific patterns for personalized care. Metabolomics offers valuable insights into the molecular mechanisms underlying DN progression and holds promise for personalized medicine approaches. Further research in this field is warranted to elucidate additional metabolic pathways and identify novel biomarkers for early detection and targeted therapeutic interventions in DN. [ABSTRACT FROM AUTHOR]

Background: In most cases, hypothyroidism is not linked to kidney disease. However, hypothyroidism has been shown to hasten the development of chronic kidney disease (CKD). Aim of the Work: to evaluate thyroid abnormalities in patients with end stage renal disease in a sample of Egyptian populations. Patients and Methods: This study was conducted with 70 Egyptian Patients selected from Nephrology department in Theodor Bilharz Research Institute, in a case control study, they were categorized into 2 groups Group 1: Stage V renal disease group (n = 40): patients with eGFR <15mL/min with no history of thyroid disease or receiving any thyroid medications. Group 2: Age and sex matched health population group (n = 30): with normal renal function with no history of thyroid disease or receiving any thyroid medications. All subjects underwent full thyroid profile, and estimated GFR. Results: Symptoms of thyroid dysfunction were more frequent in end stage group, the difference statistically were significant only in muscle weakness. TSH was statistically significantly higher in cases with hypothyroidism. TGABs were statistically significantly higher in cases with hypothyroidism. Antimicrosomal antibodies recorded only in hypothyroid cases, the differences were statistically significant. FT3, TSH, TGABs and thyroid volume statistically had perfect diagnostic performance in diagnosing hypothyroidism among end stage renal disease group. Conclusion: Frequency of hypothyroidism was higher in end stage renal disease patients compared to control group. So, it is important to keep monitoring thyroid functions in patients with advanced renal impairment that may enhance quality of life. [ABSTRACT FROM AUTHOR]

Introduction: Tuberous sclerosis complex (TSC) is a rare genetic disease, affecting TSC1 or TSC2 gene, that manifests as a multisystem disorder defined by the development of numerous benign tumors, called angiomyolipomas (AMLs). Due to TSC, mutations in the genes cause permanent activation of the mTOR pathway, leading to tumorogenicity, cellular proliferation distributed around blood vessels and lastly is mostly manifested in hemorrage. Renal complications due to TSC can lead to chronic kidney disease (CKD) and, in severe cases, endstage renal disease (ESRD), requiring renal replacement therapy. Case Report: A 35-year-old female patient known with CKD and a 10-year history of TSC, presented to Nephrology department for monthly check-up with lack of appetite, asthenia, nausea, vomiting, fatigue suggesting uremic syndrome. In 2013 an abdominal CT showed a right renal AML, giant left AML with retroperitoneal hemorrhage, indicating a mandatory left total nephrectomy. Renal AMLs can lead to complications such as local growth, mechanical pressure that is imposed on the renal parenchyma, and bleeding. In 2018, the patient was treated with Everolimus (immunosuppressant) with right kidney AML not growing further. The presence of AML on a solitary kidney, hypertension and the reduced number of nephrons precipitated the onset and progression of CKD. She developed proteinuria, possible glomerulosclerosis due to hyperfiltration on the remaining nephrons. Given all the facts, ESRD was established and a vascular access via an AV fistula was created. She was initiated in chronic hemodialysis because of severe azotemia associated with clinical symptoms. Discussions : Population-based studies found that 48-to-80 percent of patients, between ages 15-30, with TSC have kidney complications with the presence of AMLs and progression towards renal insufficiency. In patients undergoing maintenance hemodialysis, the mortality rate and morbidity burden are markedky elevated, accompanied by a diminished quality of life. Conclusions: Due to its infrequency, this case highlights the need to spread further awareness. Vigilant surveillance and therapeutic intervention targeting these renal manifestations are imperative to mitigate the risk of CKD in TSC patients. [ABSTRACT FROM AUTHOR]