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Secondary hyperparathyroidism is one of the most frequent metabolic abnormalities found in patients with chronic kidney disease. The calcium-sensing receptor senses extracellular calcium and is the principal regulator of parathyroid hormone secretion. Cloning of the calcium-sensing receptor led to the development of calcimimetics, drugs that decrease parathyroid hormone secretion through the positive allosteric modulation of this receptor. Cinacalcet was the first oral calcimimetic approved by the US Food and Drug Administration (FDA) in 2004 for the treatment of secondary hyperparathyroidism in adult patients on dialysis. Although cinacalcet has demonstrated safety and effectiveness, it has two main problems: gastrointestinal side effects that result in poor adherence, and the inhibitory action on CYP2D6 with the possibility of interactions with commonly used medications. To address the problem of oral compliance, Etelcalcetide, a small synthetic polycationic peptide IV calcimimetic was introduced in 2017. This drug showed a 10% greater decrease in serum parathyroid hormone values compared to cinacalcet but no better gastrointestinal tolerance, with greater risk of hypocalcemia. Several structural modifications were introduced in cinacalcet to produce a new compound called evocalcet. This drug, which was introduced in Japan in 2018, has considerably enhanced bioavailability and decreased both the inhibitory effect on CYP2D6 and half of the gastrointestinal side effects of cinacalcet. Finally, a novel non-peptidic injectable calcimimetic agent, upacicalcet, became available in Japan in 2021. This agent has greater clearance by hemodialysis and shows no effect on gastric emptying. More studies are needed comparing the old calcimimetics to the new ones to establish their future role in the treatment of secondary hyperparathyroidism in chronic kidney disease (CKD) G5D., (© 2024. The Author(s) under exclusive licence to Italian Society of Nephrology.)

Chronic kidney disease (CKD) has emerged as one of the leading noncommunicable diseases affecting >10% of the population worldwide. Bone and mineral disorders are a common complication among patients with CKD resulting in a poor life quality, high fracture risk, increased morbidity and cardiovascular mortality. According to Kidney Disease: Improving Global Outcomes, renal osteodystrophy refers to changes in bone morphology found in bone biopsy, whereas CKD-mineral and bone disorder (CKD-MBD) defines a complex of disturbances including biochemical and hormonal alterations, disorders of bone and mineral metabolism and extraskeletal calcification. As a result, the management of CKD-MBD should focus on the aforementioned parameters, including the treatment of hyperphosphatemia, hypocalcemia, abnormal PTH and vitamin D levels. Regarding the bone fragility fractures, osteoporosis and renal osteodystrophy, which constitute the bone component of CKD-MBD, anti-osteoporotic agents constitute the mainstay of treatment. However, a thorough elucidation of the CKD-MBD pathogenesis is crucial for the ideal personalized treatment approach. In this paper, we review the pathology and management of CKD-MBD based on the current literature with special attention to recent advances., (© 2024 The Author(s). Therapeutic Apheresis and Dialysis published by John Wiley & Sons Australia, Ltd on behalf of International Society for Apheresis and Japanese Society for Apheresis.)

Background: Lynch syndrome (LS) is the most frequent hereditary tumor syndrome and is associated with an increased risk of colorectal cancer (CRC). While gene-specific and age-specific differences are considered in patient surveillance, gender-specific risks in the development of CRC have been reported in many studies but are not consistently documented., Objective: This systematic review aims to investigate gender-specific differences in CRC development among LS patients., Material and Methods: A systematic literature search following PRISMA 2020 guidelines was conducted in the PubMed, Ovid, The Cochrane Library and Web of Science databases. A total of 688 studies were screened, and 41 met the inclusion criteria., Results: Men have a higher risk of CRC and develop CRC earlier compared to women., Conclusion: These findings indicate gender-specific differences in the risk of CRC among LS patients, although they do not currently justify separate surveillance strategies., (© 2024. The Author(s), under exclusive licence to Springer Medizin Verlag GmbH, ein Teil von Springer Nature.)

Four European Reference Networks (ERN-EYE, ERKNet, Endo-ERN, ERN-ITHACA) have teamed up to establish a consensus statement and recommendations for Bardet-Biedl syndrome (BBS). BBS is an autosomal recessive ciliopathy with at least 26 genes identified to date. The clinical manifestations are pleiotropic, can be observed in utero and will progress with age. Genetic testing has progressively improved in the last years prompting for a revision of the diagnostic criteria taking into account clinical Primary and Secondary features, as well as positive or negative molecular diagnosis. This consensus statement also emphasizes on initial diagnosis, monitoring and lifelong follow-up, and symptomatic care that can be provided to patients and family members according to the involved care professionals. For paediatricians, developmental anomalies can be at the forefront for diagnosis (such as polydactyly) but can require specific care, such as for associated neuro developmental disorders. For ophthalmology, the early onset retinal degeneration requires ad hoc functional and imaging technologies and specific care for severe visual impairment. For endocrinology, among other manifestations, early onset obesity and its complications has benefited from better evaluation of eating behaviour problems, improved lifestyle programs, and from novel pharmacological therapies. Kidney and urinary track involvements warrants lifespan attention, as chronic kidney failure can occur and early management might improve outcome. This consensus recommends revised diagnostic criteria for BBS that will ensure certainty of diagnosis, giving robust grounds for genetic counselling as well as in the perspective of future trials for innovative therapies., (© 2024. The Author(s).)

Background: Cardiovascular death is the main cause of death in patients with end-stage kidney disease (ESKD). Left ventricular hypertrophy (LVH) and left atrial diameter (LAD) enlargement are frequent cardiac alterations in patients with ESKD and are major risk factors for cardiovascular events. However, it remains unclear whether there is an association between combined LAD or LVH and all-cause or cardiovascular mortality in this population., Methods: A single-centre, retrospective cohort study including 576 haemodialysis (HD) patients was conducted. Patients were evaluated by cardiac ultrasound, and the study cohort was divided into four groups according to LAD and LVH status: low LAD and non-LVH; low LAD and LVH; high LAD and non-LVH; and high LAD and LVH. We used Kaplan-Meier analysis and Cox proportional hazard regression to analyse all-cause and cardiovascular mortality after multivariate adjustment., Results: LAD was associated with an increased risk of all-cause mortality (HR 2.371, 1.602-3.509; p < 0.001). No significant differences were found between LVH and the risk of all-cause mortality. Patients with high LAD and LVH had significantly greater all-cause and cardiovascular mortality than did those with low LAD and non-LVH after adjustments for numerous potential confounders (HR 3.080, 1.608-5.899; p = 0.001) (HR 4.059, 1.753-9.397; p = 0.001)., Conclusion: Among maintenance haemodialysis (MHD) patients, LAD was more strongly associated with mortality than was LVH. A high LAD and LVH are associated with a greater risk of mortality. Our results emphasize that the occurrence of LAD and LVH in combination provides information that may be helpful in stratifying the risk of MHD patients., (© 2024. The Author(s), under exclusive licence to Japanese Society of Nephrology.)

Aortic stiffness, measured by carotid-femoral pulse wave velocity (PWV), is a predictor of cardiovascular (CV) mortality in patients with end-stage renal disease (ESRD). Aortic stiffness increases aortic systolic and pulse pressures (cSBP, cPP) and augmentation index adjusted for a heart rate of 75 beats per minute (AIx@75). In this study, we examined if the integration of multiple components of central blood pressure and aortic stiffness (ICPS) into risk score categories could improve CV mortality prediction in ESRD. In a prospective cohort of 311 patients with ESRD on dialysis who underwent vascular assessment at baseline, 118 CV deaths occurred after a median follow-up of 3.1 years. The relationship between hemodynamic parameters and CV mortality was analyzed through Kaplan-Meier and Cox survival analysis. ICPS risk score from 0 to 5 points were calculated from points given to tertiles, and were regrouped into three risk categories (Average, High, Very-High). A strong association was found between the ICPS risk categories and CV mortality (High risk HR = 2.20, 95% CI: 1.05-4.62, P = 0.036); Very-High risk (HR = 4.44, 95% CI: 2.21-8.92, P < 0.001) as compared to the Average risk group. The Very-High risk category remained associated with CV mortality (HR = 3.55, 95% CI: 1.37-9.21, P = 0.009) after adjustment for traditional CV risk factors as compared to the Average risk group. While higher C-statistics value of ICPS categories (C: 0.627, 95% CI: 0.578-0.676, P = 0.001) was not statistically superior to PWV, cPP or AIx@75, the use of ICPS categories resulted in a continuous net reclassification index of 0.56 (95% CI: 0.07-0.99). In conclusion, integration of multiple components of central blood pressure and aortic stiffness may potentially be useful for better prediction of CV mortality in this cohort., (© 2024. The Author(s), under exclusive licence to Springer Nature Limited.)

Introduction: This study aimed to assess the effectiveness of calcimimetics in reducing the risk of fractures in dialysis patients with secondary hyperparathyroidism (SHPT)., Material and Methods: A comprehensive literature search was conducted using PubMed, Embase, and Cochrane Library for articles published through December 9, 2023. The quality of each trial was evaluated using the Cochrane Collaboration tool. Meta-analysis was performed using a random-effects model, and effect measures across studies were synthesized. The risk ratio (RR) and 95% confidence interval (CI) were used to quantify the risk of fracture., Results: We identified seven studies involving 6481 dialysis patients with SHPT. The administration of calcimimetics reduced fracture incidence compared to placebo or conventional treatment (RR: 0.50, 95% CI 0.29-0.88, p = 0.02). Calcimimetics demonstrated a low number needed to treat (NNT) to prevent an incident fracture (NNT: 47)., Conclusion: The use of calcimimetics offers a significant benefit in reducing the risk of fractures in patients undergoing dialysis with SHPT., (© 2024. The Japanese Society Bone and Mineral Research.)

Background: Left ventricular hypertrophy (LVH) is highly prevalent in haemodialysis (HD) patients and is associated with an increased risk of death. Roxadustat and recombinant human erythropoietin (rHuEPO, abbreviated as EPO) are the main treatment strategies for renal anaemia in HD patients, but it has not been clear whether there is a difference in their effect on LVH., Methods: In this multi-centre, prospective, randomized trial of 12-month duration, study participants were randomized in a 1:1 ratio to the roxadustat group or the EPO group. The doses of both treatment regimens were adjusted so that the patients had a haemoglobin level of 10.0-12.0 g per dL. The primary study endpoint was the change from baseline to 12 months in the left ventricular mass index (LVMI, g/m 2 ) measured by echocardiography., Results: In total, 114 patients were enrolled. The mean age was 50 years, and the median dialysis duration was 33 months. Sixty-one patients were men, and 24 were diabetic. LVMI decreased from 116.18 ± 27.84 to 110.70 ± 25.74 g/m 2 in the roxadustat group. However, it increased from 109.35 ± 23.41 to 114.99 ± 28.46 g/m 2 in the EPO group, with a significant difference in the change in LVMI between the two groups [-5.48 (-11.60 to 0.65) vs. 5.65 (0.74 to 10.55), p < 0.05]. Changes in left ventricular mass, end-diastolic volume and 6-min walk test seemed superior in the roxadustat group. There were no significant differences in other cardiac geometry, biochemical parameters and major adverse cardiovascular events between the two groups., Conclusions: Compared to EPO, roxadustat is more helpful in the regression of LVH in HD patients., (© 2024 The Association for the Publication of the Journal of Internal Medicine.)

Cardiovascular disease (CVD) is the leading cause of end-stage mortality in chronic kidney disease (CKD) patients. However, CVD and CKD are inextricably linked, as microalbuminuria is an independent risk factor for CVD. Herein, we investigated changes in cardiac function and its risk factors in CKD patients who had different urine albumin-to-creatinine ratios (UACRs) and estimated glomerular filtration rates (eGFRs). We prospectively enrolled 182 CKD patients, classified into three groups based on UACRs and eGFRs. Fifty healthy volunteers were included as controls. Changes in clinical and echocardiographic parameters were assessed in each group, and factors independently associated with strain parameters were further analyzed. Compared with those in the control group, the albuminuria but unimpaired renal function (ALB-CKD G1-2), albuminuria and impaired renal function (ALB-CKD G3), and normoalbuminuric CKD (NACKD) groups had decreased left ventricular (LV), right ventricular (RV), and left atrial (LA) strains, the LA contractile strain being the only statistically comparable parameter. Stepwise multiple linear regression analysis revealed varying factors independently correlating with the LV global longitudinal strain. The LA reservoir and conduit strains independently correlated with LV diastolic function in stage 3 CKD associated with comorbid albuminuria or normoalbuminuria. LV function was a partial determinant of LA and RV function in the ALB-CKD G3 group, whereas ventricular and atrial function were independent of each other in the ALB-CKD G1-2 and NACKD groups. Clinical intervention should focus on specific factors affecting cardiac function in patients to reduce the risk of CVD-related death., (© 2024. The Author(s), under exclusive licence to Springer Nature B.V.)

Background: Chronic kidney disease leads to cardiac remodelling of multifactorial origin known as "uraemic cardiomyopathy", the reversibility of which after kidney transplantation (KT) remains controversial. Our objectives were to assess, in the modern era, changes in echocardiographic parameters following KT and identify predictive clinical and biological factors associated with echocardiographic changes., Methods: One hundred six patients (mean age 48 ± 16, 73% male) who underwent KT at the University Hospital of Nancy between 2007 and 2018 were retrospectively investigated. Pre- and post-KT echocardiography findings (8.6 months before and 22 months after KT on average, respectively) were centralised, blind-reviewed and compared., Results: A majority of patients (60%) had either a left ventricular (LV) ejection fraction < 50%, at least moderately abnormal LV mass index or left atrial (LA) dilatation at pretransplanted echocardiography. After KT, LV remodelling and diastolic doppler indices did not significantly change whereas LA volume index (LAVI) increased (35.9 mL/m 2 post-KT vs. 30.9 mL/m 2 pre-KT, p = 0.006). Advancing age, cardiac valvular disease, delayed graft function, lower post-KT haemoglobin, and more severe post-KT hypertension were associated with higher LAVI after KT. Higher post-KT serum creatinine, more severe post-KT hypertension and lower pre-KT blood calcium levels were associated with a deterioration in LAVI after KT., Discussion/conclusion: Adverse remodelling of the left atrial volume occurred after KT, predominantly in patients with lower pre-KT blood calcium, poorer graft function and post-KT hypertension. These results suggest that a better management of modifiable factors such as pre-KT hyperparathyroidism or post-KT hypertension could limit post-KT cardiac remodelling., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany.)

Inorganic phosphate (Pi) is an essential component of many biologically important molecules such as DNA, RNA, ATP, phospholipids, or apatite. It is required for intracellular phosphorylation signaling events and acts as pH buffer in intra- and extracellular compartments. Intestinal absorption, uptake into cells, and renal reabsorption depend on a set of different phosphate transporters from the SLC20 (PiT transporters) and SLC34 (NaPi transporters) gene families. The physiological relevance of these transporters is evident from rare monogenic disorders in humans affecting SLC20A2 (Fahr's disease, basal ganglia calcification), SLC34A1 (idiopathic infantile hypercalcemia), SLC34A2 (pulmonary alveolar microlithiasis), and SLC34A3 (hereditary hypophosphatemic rickets with hypercalciuria). SLC34 transporters are inhibited by millimolar concentrations of phosphonoformic acid or arsenate while SLC20 are relatively resistant to these compounds. More recently, a series of more specific and potent drugs have been developed to target SLC34A2 to reduce intestinal Pi absorption and to inhibit SLC34A1 and/or SLC34A3 to increase renal Pi excretion in patients with renal disease and incipient hyperphosphatemia. Also, SLC20 inhibitors have been developed with the same intention. Some of these substances are currently undergoing preclinical and clinical testing. Tenapanor, a non-absorbable Na + /H + -exchanger isoform 3 inhibitor, reduces intestinal Pi absorption likely by indirectly acting on the paracellular pathway for Pi and has been tested in several phase III trials for reducing Pi overload in patients with renal insufficiency and dialysis., (© 2023. The Author(s), under exclusive license to Springer Nature Switzerland AG.)

Aims/Introduction: Chronic kidney disease (CKD) is a very important issue globally because of the risk of its progressing to end‐stage renal disease. We aimed to identify factors contributing to long‐term estimated glomerular filtration rate (eGFR) decline to determine an early diagnosis and prevent CKD progression. Materials and Methods: From January 2003 to December 2006, 5,507 individuals underwent health checkups at our hospital's Preventive Medicine Research Center. We ultimately enrolled 2,175 individuals. The eGFR was ≥60 mL/min/1.73 m2 at the start of observation period, which was 20 years. The event onset time was the day that the eGFR became <30 mL/min during the 20‐year period. Baseline risk factors – in particular, the effect of plasma glucose levels on the eGFR – were extracted and evaluated by using Fine and Gray analysis. Results: During the 20‐year observation, the hazard ratio (HR) of CKD progression was examined. A fasting plasma glucose (FPG) level ≥105 mg/dL was significantly associated with the risk of CKD progressing to an eGFR <30 mL/min. This trend was similar in the slope of eGFR. An FPG ≥105 mg/dL or an glycated hemoglobin level ≥6.5% was useful for intervening in CKD progression. Multivariate analysis showed that independent risk factors were an FPG level ≥105 mg/dL (HR 1.9; P < 0.001), age ≥60 years (HR 3.86; P < 0.001), obesity (HR 1.61; P < 0.01) and urinary protein (HR 1.55; P < 0.01). Conclusions: For early intervention against a reduction in the eGFR, detecting mild increases in FPG ≥105 mg/dL in patients with CKD with or without diabetes is useful. [ABSTRACT FROM AUTHOR]

Introduction: Asymmetric dimethylarginine (ADMA), a cardiovascular risk factor, increases in renal failure. The aim of this study was to investigate ADMA levels in normal weight and obese patients on hemodialysis. Methods: In this cross-sectional study, 43 normal weight and 43 obese patients on regular hemodialysis were examined. Malnutrition-inflammation score (MIS), anthropometry, circulating ADMA, lipid profiles including triglycerides (TG), total cholesterol (TC), low-density lipoprotein (LDL), high-density lipoprotein (HDL) and lipid ratios, glucose homeostasis parameters, blood pressure, and high-sensitivity C-reactive protein (hs-CRP) were assessed. Results: Serum levels of ADMA were significantly lower in the obese compared to the normal weight patients (10268.2 ± 10092.4 vs. 13765.2 ± 9951.3 ng/l, P = 0.03). At the same time MIS score (6.1 ± 2.4 vs. 10.7 ± 3.2, P < 0.001), systolic blood pressure (119 ± 26.8 vs. 134.2 ± 24.7 mmHg, P = 0.018) and mean arterial pressure (91.3 ± 18.6 vs. 100.9 ± 15.9 mmHg, P = 0.028) were significantly lower in the obese than the normal weight group. Fasting blood glucose (P = 0.045), TG/HDL (P = 0.03), TC/HDL (P = 0.019), and LDL/HDL (P = 0.005) ratios, and hs-CRP (P = 0.015) levels were significantly higher in the obese than in the normal weight group. Conclusion: Circulating ADMA was significantly lower in obese than in normal weight patients on hemodialysis, which was concomitant with lower MIS, indicating a better nutritional inflammatory status, and lower blood pressure. [ABSTRACT FROM AUTHOR]

Introduction: According to the conducted studies, breast cancer is one of the most common malignant tumors, and its incidence rate is increasing yearly. One of the measures to reduce the mentalities from breast cancer is early diagnosis of biomarkers, such as Leptin polymorphisms (rs7799039 and rs2167270), and timely treatment. Leptin is an adipocytokine made by fat cells, playing a crucial role in cell proliferation, survival, migration, and immune response. The present study aimed to assess the association between polymorphisms in the Leptin gene and breast cancer risk in Arak, Iran. Materials & Methods: Two SNPs of the Leptin gene (rs7799039 and rs2167270) were genotyped by PCR-RFLP method (polymerase chain reaction-restriction fragment length polymorphism) in a case-control study, including 80 breast cancer patients and 80 healthy controls. In this study, all statistical analyses were performed in SPSS software (version 26) using the Chi-Squared test at P˂ 0.05 significant level. Results: Based on the results, rs7799039 and rs2167270 showed no significant association with breast cancer risk (P=0.183 and P=0.86, respectively). In this study, the mean age in the patient group was 47 ( an age range of 28-79 years). Conclusion: As evidenced by the obtained results, Leptin gene polymorphisms (rs7799039 and rs2167270) did not increase the risk of breast cancer in the Arak population in Iran. Although based on the present study results, there was no significant association between Leptin gene polymorphisms and breast cancer risk, according to the prominent role of the Leptin gene, the polymorphisms of this gene could be used as biomarkers to predict breast cancer in other populations. [ABSTRACT FROM AUTHOR]

Background: For many decision makers in Health Technology Assessment the EQ-5D-5L is the standard measure of health-related quality of life (HRQL). However, evidence has shown the limitations of the measure in certain disease areas, including dermatology. Alopecia areata (AA) is associated with a significant HRQL impact, partly due to the emotional impact of hair loss. Objectives: This study explores the psychometric properties of the EQ-5D-5L in people with AA in reference to the short-form 36 version 2 (SF-36v2), the Alopecia Areata Patient Priority Outcomes (AAPPO), the Severity of Alopecia Tool (SALT) and the Patient Global Impressions of Change (PGI-C). Methods: Data from participants with AA enrolled in the ALLEGRO-2b/3 trial (NCT03732807) of ritlecitinib were analysed. Participants completed the AAPPO measure (an AA-specific measure assessing emotional symptoms and activity limitations), PGI-C, EQ-5D-5L and SF-36v2 across 48-weeks of follow up. Extent of scalp hair loss was assessed using the SALT. Ceiling effects, known groups validity, convergent validity and responsiveness were examined. Known groups were defined by SALT score and a PGI-C defined response from baseline. Exploratory factor analysis was also performed. Results: Data were available from 612 adult participants. Ceiling effects were observed for the EQ-5D-5L (55.3–61.2%) and analyses suggested that the EQ-5D did not capture important differences between patients that the SF-36v2 did. The EQ-5D-5L very weakly correlated with SALT score, whereas the AAPPO correlated more strongly with the extent of hair loss. Compared with the EQ-5D-5L, the AAPPO was better able to discriminate between known groups defined by SALT and PGI-C. An exploratory factor analysis suggested that the EQ-5D-5L had limitations in content validity compared with the AAPPO. Conclusions: The EQ-5D-5L may not adequately measure the burden of AA on patients' HRQL. Insensitivity to the burden of AA suggests that the EQ-5D-5L may not measure treatment-related benefit with hair regrowth. Data from other measures could be considered if they are shown to be more relevant. Plain Language Summary (PLS): Do frequently used health-related quality of life questionnaires accurately measure the impact of alopecia areata? Alopecia areata (AA) is a disease that causes hair loss on the scalp and, in some cases, other parts of the body. It affects 18.4 million people worldwide. We know that AA can have a significant impact on a person's health-related quality of life (HRQL). Understanding the impact of AA on HRQL is important, but frequently used questionnaires to assess HRQL may not accurately measure the impact of the condition. This study uses data from a clinical trial (ALLEGRO-2b/3 trial) conducted in patients with AA from multiple countries to examine whether frequently used HRQL questionnaires can measure the impact of AA. We compared the HRQL of people with different levels of hair loss to see how well these questionnaires measure the impact of AA. We used data from 612 participants who took part in the trial. We found that some of the frequently used questionnaires did not detect differences between people with different levels of hair loss or those who thought their condition had improved compared with those who did not, suggesting that they may not accurately measure the impact of AA. Overall, some frequently used questionnaires to assess HRQL may not be appropriate for use in people with AA. Other ways of measuring HRQL may be more appropriate for understanding the full impact of AA. [ABSTRACT FROM AUTHOR]

Introduction: Chronic Kidney Disease (CKD) is a multifaceted medical condition characterised by the gradual loss of kidney function over time, often leading to a myriad of complications affecting various organ systems in the body. Among these complications, Pulmonary Hypertension (PH) has emerged as a significant yet under-recognised co-morbidity, particularly in patients with advanced CKD stages 4 and 5. PH is defined by elevated mean Pulmonary Arterial Pressure (PAP) and increased Pulmonary Vascular Resistance (PVR). Understanding the intricate relationship between CKD and PH is essential for effective management and improved patient outcomes. Aim: To study the prevalence and severity of PH in patients with CKD stages 4 and 5 and to explore the relationship between PH and co-morbidities such as Type 2 Diabetes Mellitus (DM2) and systemic Hypertension (HTN) in these patients. Materials and Methods: This cross-sectional analysis was performed in the Department of General Medicine at Dr. D.Y. Patil Medical College, Hospital and Research Centre, Dr. D. Y. Patil Vidyapeeth (Deemed to be University), Pune, Maharashtra, India on 100 cases from September 2022 to May 2024. The patients were divided into CKD stages 4 and 5 based on the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation. PH was diagnosed based on 2D Echocardiography (ECHO) and categorised into mild, moderate and severe. Quantitative variables were compared using an unpaired t-test between CKD stages 4 and 5. Qualitative variables were compared using the Chi-square or Fisher's-exact test. Results: The mean age of the study participants was 56.25±12.45 years. A total of 66% of the study participants were diagnosed with stage 4 CKD. In this study, a statistically non significant association was seen between the stages of CKD and the grades of PH (p-value=0.74). No significant association was found between diabetes and PH (p-value=0.97) in CKD stages 4 and 5. The median Pulmonary Artery Systolic Pressure (PASP) was found to be higher in non diabetics and non hypertensives in CKD stages 4 and 5 and this was statistically significant (p<0.0001). Conclusion: The prevalence of PH among CKD patients was 78%. However, the severity of PH was not found to be significantly associated with the severity of CKD. Co-morbidities were present in a substantial number of cases, but no significant correlation was identified. [ABSTRACT FROM AUTHOR]

Anemia is a common but often underdiagnosed and undertreated geriatric syndrome in hospitalized older patients. In this retrospective multicenter study, we aimed at characterizing the prevalence, risk factors, diagnostic and treatment approach to anemia in older patients admitted to acute care hospitals, focusing on differences between nephrology and geriatrics units. Prevalence and risk factors for anemia, diagnostic inertia (lack of iron, vitamin B12, and folate status assessment), replacement inertia (omitted treatment with iron, vitamin B12 or folic acid), and erythropoiesis-stimulating agents (ESA) inertia were explored. 1963 patients aged 82.7 (6.8) years were included in the study; 66.7% of the study population had anemia; among anemic patients, diagnostic inertia and replacement inertia were common with rates of 22–31% and 50–87%, respectively; omitted treatment with ESA affected 67.2% of patients and was more prevalent in geriatric units. In most cases, patients with ESA inertia were not routinely screened for iron tests. COPD, cancer, eGFR 45–60 ml/min were associated with increased tendency to ESA inertia. In conclusion, anemia had a high prevalence in older patients discharged from acute care units, but it is often underdiagnosed and undertreated. [ABSTRACT FROM AUTHOR]

Objectives: To apply cardiac magnetic resonance imaging (CMR) for detailed myocardial characterization in uremic cardiomyopathy (UC), hypertensive cardiomyopathy (HTN), and hypertrophic cardiomyopathy (HCM) aiming to enrich the understanding of UC's etiology and further support the development of therapeutic strategies. Methods: A total of 152 patients (age: 49.2 ± 9.9 years; 65.8% male) underwent routine CMR from June 2016 to March 2023. Retrospectively, 53 patients with UC, 39 patients with HTN, 30 patients with HCM, and 30 healthy controls were included. Functional analysis, feature tracking of the left ventricle and left atrium, and myocardial T1, T2, and T2* mapping were performed. Statistical analysis included Pearson correlation and ROC analysis to define correlations and discriminators between groups. Results: UC patients demonstrated significantly higher native T1 (p < 0.001 for all) and T2 (p < 0.002 for all) values compared with the other three groups. UC patients revealed higher left atrial reservoir strain rate (p < 0.001 for all) and left atrial conduit strain rate (p < 0.001 for all) absolute values as compared with HTN and HCM patients. A significant correlation between T1 and T2 values in UC patients (r = 0.511, p < 0.001) was found. The combination of T1 values and strain parameters was the best discriminator between UC and HTN patients (AUC = 0.872, 95% CI: 0.801–0.943) and between UC and HCM patients (AUC = 0.840, 95% CI: 0.746–0.934). Conclusion: UC reveals distinguishing tissue characteristics as evidenced by T1 and T2 mapping, as well as distinguishing functional strain parameters as compared with other hypertrophic phenotypes such as HTN and HCM. Critical relevance statement: The use of CMR imaging in UC patients offers incremental information to elucidate its complex etiology, contributing to ongoing discourse on effective treatment pathways. Key Points: This study investigated uremic, hypertensive, and hypertrophic cardiomyopathies using cardiac MRI. UC patients have higher T1 and T2 values and better preserved cardiac function. Combined strain and T1 values distinguish UC from other cardiomyopathies. [ABSTRACT FROM AUTHOR]

Newfoundland and Labrador (NL) has a long history of resource development, exploitation, and frequent mismanagement. Even before joining the Canadian confederation in 1949, industries such as mining, fishing, and forestry had significantly shaped the province. Recently, a new "resource" has been recognized: NL's genetic data, often described as a "genetic gold mine" and "the new oil." These analogies reflect the perception of genetic data as a valuable resource, resonating in a province historically reliant on resource extraction. Since the early 2000s, NL's genetic data has been recognized as a unique asset, prompting provincial reports on its management. Renewed interest has emerged with a local biotechnology company aiming to leverage NL's unique genetic architecture. This paper examines the implications of conceptualizing genetic information as a resource, exploring how this fits within existing resource development frameworks and policies, and considering its potential to shape policies for managing the benefits and burdens of genetic data exploitation. I conclude that while the NL genome is not a natural resource in the traditional sense, the province nevertheless needs to take more direct responsibility for its development and to ensure that any potential benefits from exploiting it are shared with the population. [ABSTRACT FROM AUTHOR]

Aims: Renal dysfunction in patients with chronic heart failure predicts a poor prognosis. Tolvaptan has a diuretic effect in patients with chronic kidney disease and heart failure without adverse effects on renal function. We aimed to determine the effects of tolvaptan and predictors of worsening renal function in patients with heart failure. Methods and results: This post hoc analysis was a sub‐analysis of a single‐centre prospectively randomized trial on the early and short‐term tolvaptan administration. We enrolled 201 participants with decompensated heart failure between January 2014 and March 2019 (early group, n = 104; age: 79.0 ± 12.8 years; late group, n = 97; age: 80.3 ± 10.8 years). Renal ultrasonography was performed before and after the administration of tolvaptan. Urine output and oral water intake significantly increased during tolvaptan administration. The difference between water intake and urine volume increased during tolvaptan administration. Changes in body weight, blood pressure, heart rate, and estimated glomerular filtration rate (eGFR) in both groups were comparable. The changes in peak‐systolic velocity (PSV), acceleration time (AT) of the renal arteries, and resistance index were comparable. The changes in PSV and end‐diastolic velocity (EDV) of the interlobar arteries increased following tolvaptan administration (Δmax PSV: 0.0 ± 14.8 cm/s before tolvaptan vs. 5.6 ± 15.7 cm/s after tolvaptan, P = 0.002; Δmean PSV: 0.4 ± 12.3 vs. 4.9 ± 12.7 cm/s, P = 0.002; Δmax EDV: −0.2 ± 3.5 vs. 1.4 ± 4.0 cm/s, P = 0.001; Δmean EDV: −0.0 ± 3.1 vs. 1.1 ± 3.4 cm/s, P = 0.003). The renal artery AT was negatively correlated with the eGFR (Δmax AT: beta = −0.2354, P = 0.044; Δmean AT: beta = −0.2477, P = 0.035). Conclusions: Tolvaptan increased the PSV and EDV of the interlobar artery, which may mean tolvaptan increased renal blood flow. The renal artery AT may be a surrogate for worsening renal function. [ABSTRACT FROM AUTHOR]

Purpose: The aim of this study was to analyze the effect of chronic kidney disease (CKD) on the short-term outcomes and prognosis of colorectal cancer (CRC) patients who underwent primary surgery. Methods: CRC patients who underwent radical surgery were included from Jan 2011 to Jan 2020 in a single hospital. The short-term outcomes and prognosis were compared between the CKD group and the Non-CKD group using propensity score matching (PSM) analysis. Results: A total of 4056 patients undergoing CRC surgery were included, including 723 patients in the CKD group and 3333 patients in the Non-CKD group. After 1:1 PSM, there were 666 patients in each group, respectively. No significant difference was found in baseline characteristics between the two groups. (p>0.05). After PSM, the CKD group had a longer postoperative hospital stay (P=0.009) and a higher incidence of overall complications (p=0.050). Cox analysis was performed on matched patients to find predictors of overall survival (OS) and disease-free survival (DFS). We found that age (p<0.01, HR=1.045, 95% CI=1.028-1.062), tumor stage (p<0.01, HR=1.931, 95% CI=1.564-2.385) and overall complications (p<0.01, HR=1.858, 95% CI=1.423-2.425) were independent predictors of OS. Age (p<0.01, HR=1.034, 95% CI=1.020-1.049), tumor stage (p<0.01, HR=1.852, 95% CI=1.537-2.231), and overall complications (p<0.01, HR=1.651, 95% CI=1.295-2.10) were independent predictors of DFS. However, CKD was not an independent predictor of OS or DFS (OS: p=0.619, HR=1.070, 95% CI=0.820-1.396; DFS: p=0.472, HR=1.092, 95% CI=0.859-1.389). Conclusion: CKD prolonged postoperative hospital stay; however, CKD might not affect major postoperative complications, OS or DFS of CRC. [ABSTRACT FROM AUTHOR]

Obesity is a major public health issue due to its association with type 2 diabetes, hypertension, and other cardiovascular risks. The BBSome, a complex of eight conserved Bardet–Biedl syndrome (BBS) proteins, has emerged as a key regulator of energy and glucose homeostasis as well as cardiovascular function. However, the importance of adipocyte BBSome in controlling these physiological processes is not clear. Here, we show that adipocyte-specific constitutive disruption of the BBSome through selective deletion of the Bbs1 gene adiponectin (AdipoCre/Bbs1fl/fl mice) does not affect body weight under normal chow or high-fat and high-sucrose diet (HFHSD). However, constitutive BBSome deficiency caused impairment in glucose tolerance and insulin sensitivity. Similar phenotypes were observed after inducible adipocyte-specific disruption of the BBSome (AdipoCreERT2/Bbs1fl/fl mice). Interestingly, a significant increase in renal sympathetic nerve activity, measured using multifiber recording in the conscious state, was observed in AdipoCre/Bbs1fl/fl mice on both chow and HFHSD. A significant increase in tail-cuff arterial pressure was also observed in chow-fed AdipoCre/Bbs1fl/fl mice, but this was not reproduced when arterial pressure was measured by radiotelemetry. Moreover, AdipoCre/Bbs1fl/fl mice had no significant alterations in vascular reactivity. On the other hand, AdipoCre/Bbs1fl/fl mice displayed impaired baroreceptor reflex sensitivity when fed HFHSD, but not on normal chow. Taken together, these data highlight the relevance of the adipocyte BBSome for the regulation of glucose homeostasis and sympathetic traffic. The BBSome also contributes to baroreflex sensitivity under HFHSD, but not normal chow. NEW & NOTEWORTHY: The current study show how genetic manipulation of fat cells impacts various functions of the body including sensitivity to the hormone insulin. [ABSTRACT FROM AUTHOR]

Background The haemodialysis (HD) population is sedentary, with substantial cardiovascular disease risk. In the general population, small increases in daily step count associate with significant reductions in cardiovascular mortality. This study explores the relationship between daily step count and surrogate markers of cardiovascular disease, including left ventricular ejection fraction (LVEF) and native T1 (a marker of diffuse myocardial fibrosis), within the HD population. Methods This was a post hoc analysis of the association between daily step count and metabolic equivalent of task (MET) and prognostically important cardiac magnetic resonance imaging parameters from the CYCLE-HD study (ISRCTN11299707). Unadjusted linear regression and multiple linear regression adjusted for age, body mass index, dialysis vintage, haemoglobin, hypertension and ultrafiltration volume were performed. Significant relationships were explored with natural cubic spline models with four degrees of freedom (five knots). Results A total of 107 participants were included [age 56.3 ± 14.1 years, 79 (73.8%) males]. The median daily step count was 2558 (interquartile range 1054–4352). There were significant associations between steps and LVEF (β = 0.292; P  = .009) and steps and native T1 (β = −0.245; P  = .035). Further modelling demonstrated most of the increase in LVEF occurred at up to 2000 steps/day and there was an inverse dose–response relationship between steps and native T1, with the most pronounced reduction in native T1 between ≈2500 and 6000 steps/day. Conclusions The results suggest an association between daily step count and parameters of cardiovascular health in the HD population. These findings support the recommendations for encouraging physical activity but are not the justification. Further research should evaluate whether a simple physical activity intervention improves cardiovascular outcomes in individuals receiving maintenance HD. [ABSTRACT FROM AUTHOR]

Background: Anaemia is a common but treatable condition that predicts adverse clinical outcomes. However, standards of anaemia management vary considerably. Aim: To estimate the prevalence of anaemia and extent of screening for common underlying causes in the healthcare system in the Republic of Ireland. Design & setting: We conducted a retrospective cohort study of 112 181 adult patients, aged ≥18 years, who had a full blood count performed in 2013, using data from the National Kidney Disease Surveillance System. Method: The prevalence of anaemia was determined across demographic and clinical subgroups, according to World Health Organization (WHO) definitions. The proportion screened for iron, vitamin B12, and folate deficiency was determined within a 3-month follow-up period and the corresponding prevalence for each deficiency determined. Results: The overall prevalence of anaemia was 12.0% (95% confidence interval [CI] = 11.8% to 12.2%) and was higher in women than men (13.2% versus 10.5%, P<0.001). Anaemia increased with advancing age (33.4% for those aged >75 years) and worsening kidney function (8.2%, 10.9%, 33.2%, and 63.8% for each estimated glomerular filtration rate [eGFR] categories >90, 60–89, 30–59 and <30 ml/min/1.73 m², respectively, P<0.001). After 3-months' follow-up, the proportion screened for iron deficiency was 11.2% based on transferrin saturation and 33.7% using serum ferritin. Screening for folate and B12 deficiency was 17.6% and 19.8%, respectively. Among screened patients, the prevalence of iron deficiency, B12, and folate deficiency was 37.0%, 6.3%, and 5.8%, respectively. Conclusion: The burden of anaemia in the healthcare system is substantial especially for older patients and those with advanced kidney disease. Low screening rates for iron, B12, and folate deficiency are common and warrant quality improvement initiatives. [ABSTRACT FROM AUTHOR]

Objective: To determine the impacts to research the impacts of pain's Specialized Pain Management Nursing Care in the perioperative period on pain symptoms and life quality of patients experiencing minimally invasive surgery for spinal injury. Method: Eighty patients with a spinal injury who underwent minimally invasive surgery in the Department of Orthopedics of Baoding No.1 Hospital from January 2018 to December 2021 were retrospectively analyzed. They were split into two groups following different nursing methods (n=40 each group). Specialized Pain Management Nursing Care were given to patients in the observation group. Those in the control group were given treated with routine care. Their pain score and nursing effect were compared, after which their quality of life, daily living ability and complication rate compared and analyzed. Results: The pain degree in the control group was considerably more than that in the observation group in the 1st postoperative period. The pain degree, which decreased in both groups, slumped more significantly in the observation group on the 2nd and 3rd postoperative days. The postoperative hospital stays and pain duration in the observation group were shorter than those in the control group (P<0.05), and the nursing effect was significantly better than that in the control group (P<0.05). After postoperative nursing intervention. Conclusion: Minimally invasive surgery integrated with the Specialized Pain Management Nursing Care can remarkably ameliorate pain after spinal injury surgery, reducing complications' incidence, and improving the life quality for patients. [ABSTRACT FROM AUTHOR]

Purpose: The occurrence of a second primary cancer (SPC) after primary esophageal carcinoma (EC) or gastric cardia carcinoma(GCC) is well acknowledged. However, previous research on the risk of SPC among these patients has been predominantly conducted in Asian countries. Yet, notable population-dependent variation in histological types and risk profiles exists. This register-based study assesses the histology-specific risk of SPC among individuals initially diagnosed with a first primary EC or GCC. Patients and Methods: We obtained data on 7197 patients diagnosed with EC/GCC in Finland between 1980 and 2022 from the Finnish Cancer Registry. Standardized incidence ratios (SIR) of SPC were subsequently calculated relatively to the cancer risk of the general population. Results: The average and median follow-up times were 2.8 years and 10.5 months. Adenocarcinomas and squamous cell carcinomas comprised 57.8% (n = 4165) and 36.6% (n = 2631) of all cases, respectively. An increased SIR was noted among EC/GCC patients after 15– 20 years of follow-up (SIR 1.49, 95% CI: 1.01– 2.11). Among adenocarcinoma patients, an increased SIR for SPCs of the digestive organs was seen in the 40– 54-year-old group (SIR 9.86, 95% CI: 3.62– 21.45). Squamous cell carcinoma patients displayed increased SIRs for cancer of the mouth/pharynx (SIR 3.20, 95% CI: 1.17– 6.95) and respiratory organs (1.77, 1.07– 2.76). Conclusion: Healthcare professionals should be aware of the increased risk of SPCs occurring in the mouth/pharynx, respiratory and digestive organs in survivors of EC/GCC. Patients should be advised about this risk and remain alert for symptoms, even beyond the standard 5-year follow-up period. [ABSTRACT FROM AUTHOR]

Objective: Preeclampsia (PE) is a pregnancy-related multi-organ disease and a significant cause of incidence rate and mortality of pregnant women and newborns worldwide. Delivery remains the only available treatment for PE. This study aims to establish a dynamic prediction model for PE. Methods: A total of 737 patients who visited our hospital from January 2021 to June 2022 were identified according to the inclusion and exclusion criteria, forming the primary dataset. Additionally, 176 singleton pregnant women who visited our hospital from July 2022 to November 2022 comprised the verification set. We investigated different gestational weeks of sFlt-1/PLGF (soluble FMS-like tyrosine kinase-1, placental growth factor) ratio combined with maternal characteristics and routine prenatal laboratory results in order to predict PE in each trimester. Multivariate logistic regression was used to establish the prediction model for PE at different gestational weeks. The discrimination, calibration, and clinical validity were utilized to evaluate predictive models as well as models in external validation queues. Results: At 20–24 weeks, the obtained prediction model for PE yielded an area under the curve of 0.568 (95% confidence interval, 0.479–0.657). At 25–29 weeks, the obtained prediction model for PE yielded an area under the curve of 0.773 (95% confidence interval, 0.703–0.842)and 0.731 (95% confidence interval, 0.653–0.809) at 30–34 weeks. After adding maternal factors, uterine artery pulsation index(Ut-IP), and other laboratory indicators to the sFlt-1/PLGF ratio, the predicted performance of PE improved. It found that the AUC improved to 0.826(95% confidence interval, 0.748 ∼ 0.904) at 20–24 weeks, 0.879 (95% confidence interval, 0.823 ∼ 0.935) at 25–29 weeks, and 0.862(95% confidence interval, 0.799 ∼ 0.925) at 30–34 weeks.The calibration plot of the prediction model indicates good predictive accuracy between the predicted probability of PE and the observed probability. Furthermore, decision-curve analysis showed an excellent clinical application value of the models. Conclusion: Using the sFlt-1/PLGF ratio combined with multiple factors at 25–29 weeks can effectively predict PE, but the significance of re-examination in late pregnancy is not significant. [ABSTRACT FROM AUTHOR]

Background: Patients with end-stage renal disease (ESRD) who are on hemodialysis (HD) have reduced vascular compliance and are likely to develop heart failure (HF). In this study, we estimated the prevalence of HF pre- and post-HD in ESRD using the current guidelines. Methods: We prospectively investigated HF in ESRD patients on HD using echocardiography pre- and post-HD. We used the structural and functional abnormality criteria of the 2021 European Society of Cardiology guidelines. Results: A total of 54 patients were enrolled. The mean age was 62.6 years, and 40.1% were male. Forty-five patients (83.3%) had hypertension, 28 (51.9%) had diabetes, and 20 (37.0%) had ischemic heart disease. The mean N-terminal-pro brain natriuretic peptide BNP (NT-proBNP) level was 12,388.8 ± 2,592.2 pg/dL. The mean ideal body weight was 59.3 kg, mean hemodialysis time was 237.4 min, and mean real filtration was 2.8 kg. The mean left ventricular ejection fraction (LVEF) was 62.4%, and mean left ventricular end-diastolic diameter was 52.0 mm in pre-HD. Post-HD echocardiography showed significantly lower left atrial volume index (33.3 ± 15.9 vs. 40.6 ± 17.1, p = 0.030), tricuspid regurgitation jet V (2.5 ± 0.4 vs. 2.8 ± 0.4 m/s, p < 0.001), and right ventricular systolic pressure (32.1 ± 10.3 vs. 38.4 ± 11.6, p = 0.005) compared with pre-HD. There were no differences in LVEF, E/E′ ratio, or left ventricular global longitudinal strain. A total of 88.9% of pre-HD patients and 66.7% of post-HD patients had either structural or functional abnormalities in echocardiographic parameters according to recent HF guidelines (p = 0.007). Conclusions: Our data showed that the majority of patients undergoing hemodialysis satisfy the diagnostic criteria for HF according to current HF guidelines. Pre-HD patients had a 22.2% higher incidence in the prevalence of functional or structural abnormalities as compared with post-HD patients. [ABSTRACT FROM AUTHOR]

Autosomal dominant polycystic kidney disease (ADPKD) is a genetic kidney disease with high phenotypic variability. Furthering insights into patients' ADPKD progression could lead to earlier detection, management, and alter the course to end stage kidney disease (ESKD). We sought to identify patients with rapid decline (RD) in kidney function and to determine clinical factors associated with RD using a data-driven approach. A retrospective cohort study was performed among patients with incident ADPKD (1/1/2002-12/31/2018). Latent class mixed models were used to identify RD patients using differences in eGFR trajectories over time. Predictors of RD were selected based on agreements among feature selection methods, including logistic, regularized, and random forest modeling. The final model was built on the selected predictors and clinically relevant covariates. Among 1,744 patients with incident ADPKD, 125 (7%) were identified as RD. Feature selection included 42 clinical measurements for adaptation with multiple imputations; mean (SD) eGFR was 85.2 (47.3) and 72.9 (34.4) in the RD and non-RD groups, respectively. Multiple imputed datasets identified variables as important features to distinguish RD and non-RD groups with the final prediction model determined as a balance between area under the curve (AUC) and clinical relevance which included 6 predictors: age, sex, hypertension, cerebrovascular disease, hemoglobin, and proteinuria. Results showed 72%-sensitivity, 70%-specificity, 70%-accuracy, and 0.77-AUC in identifying RD. 5-year ESKD rates were 38% and 7% among RD and non-RD groups, respectively. Using real-world routine clinical data among patients with incident ADPKD, we observed that six variables highly predicted RD in kidney function. [ABSTRACT FROM AUTHOR]

Parathyroid hormone (PTH) and fibroblast growth factor 23 (FGF23) each play a central role in the pathogenesis of chronic kidney disease (CKD)-mineral and bone disorder. Levels of both hormones increase progressively in advanced CKD and can lead to damage in multiple organs. Secondary hyperparathyroidism (SHPT), characterized by parathyroid hyperplasia with increased PTH secretion, is associated with fractures and mortality. Emerging evidence suggests that these associations may be partially explained by PTH-induced browning of adipose tissue and increased energy expenditure. Observational studies suggest a survival benefit of PTHlowering therapy, and a recent study comparing parathyroidectomy and calcimimetics further suggests the importance of intensive PTH control. The mechanisms underlying the regulation of FGF23 secretion by osteocytes in response to phosphate load have been unclear, but recent experimental studies have identified glycerol-3-phosphate, a byproduct of glycolysis released by the kidney, as a key regulator of FGF23 production. Elevated FGF23 levels have been shown to be associated with mortality, and experimental data suggest off-target adverse effects of FGF23. However, the causal role of FGF23 in adverse outcomes in CKD patients remains to be established. Further studies are needed to determine whether intensive SHPT control improves clinical outcomes and whether treatment targeting FGF23 can improve patient outcomes. [ABSTRACT FROM AUTHOR]