Kidney & blood pressure research最新文献

Introduction: We aimed to evaluate the prognostic impact of renal insufficiency and fluctuation of glomerular filtration observed during hospitalization for heart failure (HF).

Methods: We followed 3,639 patients hospitalized for acute HF and assessed the mortality risk associated with moderate or severe renal insufficiency, either permanent or transient.

Results: After adjustment, severe renal failure defined as estimated glomerular filtration (eGFR) <30 mL/min indicates ≈60% increase in 5-year mortality risk. Similar risk also had patients with only transient decline of eGFR to this range. In contrast, we did not observe any apparent mortality risk attributable to mild/moderate renal insufficiency (eGFR 30-59.9 mL/min), regardless of whether it was transient or permanent.

Conclusion: Even transient severe renal failure during hospitalization indicates poor long-term prognosis of patients with manifested HF. In contrast, only moderate renal insufficiency observed during hospitalization has no additive long-term mortality impact.

Introduction: Upper urinary tract stones combined with parenchymal infiltrative renal pelvic cancer are challenging to detect on imaging and to evaluate the differential diagnosis.

Case presentation: The symptoms and diagnoses in three cases of parenchymal infiltrative renal pelvic cancer and upper urinary tract stones that occurred between June 2019 and June 2022 were reviewed. Primary symptoms of lumbar discomfort and hematuria were evident in all 3 patients. Preoperative computed tomography (CT) abdominal imaging revealed that all three cases had hydronephrosis along with renal stones, while the other two cases only had localized hypoenhancement of the renal parenchyma, which was only thought to be limited inflammatory changes in the renal cortex as a result of the combination of renal pelvis infection. After percutaneous nephrolithotomy or ureteroscopic lithotripsy, a combined renal pelvis tumor was discovered in all of these instances. Radical tumor surgery was later performed. One patient who had several tumor metastases passed away 6 months after surgery. A case with multiple metastases was discovered 15 months after surgery and survived with the help of the current chemotherapy. A case with a bladder tumor recurrence was discovered 16 months after surgery and had transurethral bladder tumor electrosurgery and routine bladder perfusion chemotherapy.

Conclusion: Upper urinary tract stones and parenchymal infiltrative pyel carcinoma have atypical imaging, easily confused with infectious diseases. CT or computed tomography urography (CTU) must be considered by urologists. Patients who have a CT with local renal parenchyma density should be suspected of having parenchymal invasive renal pelvis carcinoma; a needle biopsy ought to be performed; and repeat biopsies may be performed if necessary. High-risk individuals need multiple, sufficient biopsies as needed and a comprehensive intraoperative assessment of the renal pelvic mucosa.

Introduction: Acute kidney injury (AKI) is a common clinical syndrome associated with high morbidity and mortality. Inhibition of the methyltransferase enhancer of zeste homolog 2 (EZH2) by its inhibitor 3-deazaneplanocin A (3-DZNeP) exerts renal benefits in acute renal ischemia-reperfusion injury (IRI). However, the underlying mechanisms are not completely known. This study aimed to elucidate the pathological mechanism of EZH2 in renal IRI by combination of multi-omics analysis and expression profiling in a public clinical cohort.

Methods: In this study, C57BL/6 J mice were used to establish the AKI model, which were treated with 3-DZNeP for 24 h. Kidney samples were collected for RNA-seq analysis, which was combined with publicly available EZH2 chromatin immunoprecipitation sequencing (ChIP-seq) data of mouse embryonic stem cell for a joint analysis to identify differentially expressed genes. Several selected differentially expressed genes were verified by quantitative PCR. Finally, single-nucleus sequencing data and expression profiling in public clinical datasets were used to confirm the negative correlation of the selected genes with EZH2 expression.

Results: 3-DZNeP treatment significantly improved renal pathology and function in IRI mice. Through RNA-seq analysis combined with EZH2 ChIP-seq database, 162 differentially expressed genes were found, which might be involved in EZH2-mediated pathology in IRI kidneys. Four differential expressed genes (Scd1, Cidea, Ghr, and Kl) related to lipid metabolism or cell growth were selected based on Gene Ontology and Kyoto Encyclopedia of Genes and Genome enrichment analysis, which were validated by quantitative PCR. Data from single-nucleus RNA sequencing revealed the negative correlation of these four genes with Ezh2 expression in different subpopulations of proximal tubular cells in IRI mice in a different pattern. Finally, the negative correlation of these four genes with EZH2 expression was confirmed in patients with AKI in two clinical datasets.

Conclusions: Our study indicates that Scd1, Cidea, Ghr, and Kl are downstream genes regulated by EZH2 in AKI. Upregulation of EZH2 in AKI inhibits the expression of these four genes in a different population of proximal tubular cells to minimize normal physiological function and promote acute or chronic cell injuries following AKI.

Introduction: Patients with idiopathic membranous nephropathy (IMN) are particularly susceptible to thromboembolism (TE). The phospholipase A2 receptor (PLA2R) antibody (Ab) has been indicated to work as an independent risk predictor for venous TE in IMN. This study aimed to further explore the predictive value of PLA2R Ab for both venous and arterial TE in IMN patients.

Methods: A total of 91 IMN patients were retrospectively selected and divided into anti-PLA2R-positive or anti-PLA2R-negative groups according to the anti-PLA2R Ab titer (cutoff: 20 RU/mL). Serum PLA2R Abs were estimated using ELISA. Anti-PLA2R-positive IMN patients were further assigned into two groups based on the presence or absence of TE.

Results: Twelve (18.18%) IMN patients with anti-PLA2R positivity had TE, including both venous and arterial TE. No TE occurred in the anti-PLA2R-negative group. IMN patients in the anti-PLA2R-positive group had significantly higher levels of total cholesterol and low-density lipoprotein than those in the anti-PLA2R-negative group. No significant difference was observed in the anti-PLA2R Ab titer between patients with and without TE. Patients with TE were significantly older than those without TE.

Conclusion: This study demonstrates that the positive status of anti-PLA2R Abs contributes to thrombosis formation in IMN.

Background: Cancer patients are prone to developing acute kidney disease (AKD), yet this phenomenon remains understudied compared to acute kidney injury (AKI). AKD, which often develops insidiously, can cause treatment interruptions, extended hospital stays, and increased mortality.

Summary: This perspective article explores the intricate relationship between AKD and cancer, focusing on prevalence, risk factors, implications for anticancer therapy, and long-term outcomes, including chronic kidney disease progression.

Key messages: To emphasize the importance of early detection and intervention, this work advocates for increased research and awareness among clinicians to improve patient outcomes and manage healthcare burdens associated with AKD in cancer patients.

Background: Physical exercise (PE) can regulate inflammation, cardiovascular health, sarcopenia, anaemia, and bone health in the chronic kidney disease (CKD) population. Experimental and clinical studies both help us better understand the mechanisms that underlie the beneficial effects of the exercise, especially in renal anaemia and CKD-mineral bone disorders (CKD-MBDs). Here, we summarize this evidence, exploring the biological pathways involved, locally released substances, and crosstalk between tissues, but also the shortcomings of current knowledge.

Summary: Anaemia: Both in healthy and CKD subjects, PE may mimic hypoxia, inhibiting PHDs; so hydroxylate HIF-α subunits may be translocated into the nucleus, resulting in dimerization of HIF-1α and HIF-1β, recruitment of p300 and CBP, and ultimately, binding to HREs at target genes to cause activation. However, in CKD subjects acute PE causes higher levels of lactate, leading to iron restriction by upregulating hepatic hepcidin expression, while chronic PE allows an increased lactate clearance and HIF-α and VEGFα levels, stimulating both erythropoiesis and angiogenesis.

Ckd-mbd: PE may improve bone health decreasing bone resorption and increasing bone formation throughout at least three main pathways: (a) increasing osteoprotegerin and decreasing RANKL system; (b) decreasing cytokine levels; and (c) stimulating production of myokines and adipokines.

Key messages: Future research needs to be defined to develop evidence-based exercise guidance to provide optimal benefit for CKD using exercise interventions as adjuvant therapy for CKD-related complications such as anaemia and CKD-MBD.

Introduction: The aims of this study are to explore the factors affecting mild cognitive impairment in patients with chronic kidney disease (CKD) who are not undergoing dialysis and to construct and validate a nomogram risk prediction model.

Methods: Using a convenience sampling method, 383 non-dialysis CKD patients from two tertiary hospitals in Chengdu were selected between February 2023 and August 2023 to form the modeling group. The patients were divided into a mild cognitive impairment group (n = 192) and a non-mild cognitive impairment group (n = 191), and factors such as demographics, disease data, and sleep disorders were compared between the two groups. Univariate and multivariate binary logistic regression analyses were used to identify independent influencing factors, followed by collinearity testing, and construction of the regression model. The final risk prediction model was presented through a nomogram and an online calculator, with internal validation using Bootstrap sampling. For external validation, 137 non-dialysis CKD patients from another tertiary hospital in Chengdu were selected between October 2023 and December 2023.

Results: In the modeling group, 192 (50.1%) of the non-dialysis CKD patients developed mild cognitive impairment, and in the validation group, 56 (40.9%) patients developed mild cognitive impairment, totaling 248 (47.7%) of all sampled non-dialysis CKD patients. Age, educational level, Occupation status, Use of smartphone, sleep disorders, hemoglobin, and platelet count were independent factors influencing the occurrence of mild cognitive impairment in non-dialysis CKD patients (all p < 0.05). The model evaluation showed an area under the ROC curve of 0.928, 95% CI (0.902, 0.953) in the modeling group, and 0.897, 95% CI (0.844, 0.950) in the validation group. The model's Youden index was 0.707, with an optimal cutoff value of 0.494, sensitivity of 0.853, and specificity of 0.854, indicating good predictive performance; calibration curves, Hosmer-Lemeshow test, and clinical decision curves indicated good calibration and clinical benefit. Internal validation results showed a consistency index (C-index) of 0.928, 95% CI (0.902, 0.953).

Conclusion: The risk prediction model developed in this study shows excellent performance, demonstrating significant predictive potential for early screening of mild cognitive impairment in non-dialysis CKD patients. The application of this model will provide a reference for healthcare professionals, helping them formulate more targeted intervention strategies to optimize patient treatment and management outcomes.

Introduction: Apela has a wide range of biological effects on the cardiovascular system, but the changes and significance of endogenous Apela in patients with chronic heart failure (CHF) and acute deterioration of cardiac and renal function are unclear.

Methods: A total of 69 patients with stable CHF combined with well-preserved renal function were enrolled and followed for 12 months. The effects of Apela on human renal glomerular endothelial cells (hRGEC), human glomerular mesangial cells (hMC), and human renal tubular epithelial cells (HK-2) were observed.

Results: Serum Apela concentration was positively correlated with NYHA class (r = 0.711) and N-terminal pro-brain natriuretic peptide (NT-proBNP) concentration (r = 0.303) but negatively correlated with left ventricular ejection fraction (LVEF) (r = -0.374) and 6-min walk distance (r = -0.860) in patients with stable CHF. Twenty-one patients experiencing deterioration of renal and cardiac function were diagnosed with cardiorenal syndrome (CRS) during the follow-up period. In addition, the serum Apela, as well as the difference in Apela between stable and worsening phases (ΔApela), was correlated with the estimated glomerular filtration rate (eGFR) and ΔeGFR in patients with CRS. Apela significantly inhibited the upregulated expression of MCP-1 and TNF-α induced by angiotensin II (AngII) in hRGEC, hMC, and HK-2 cells. Apela inhibited the adhesion of THP-1 cells to hRGEC and promoted the tubular formation of hRGEC. Moreover, Apela enhanced the expression of MMP-9 in hMC but inhibited the upregulated expression of α-SMA and vimentin in HK-2 cells by AngII.

Conclusion: This study suggests that the level of Apela can be used to diagnose heart failure and assess the severity of cardiac dysfunction in patients with stable CHF, and its dynamic changes can be used to evaluate the damage to renal function in patients with CRS. Apela plays multiple protective effects on renal cells, highlighting its clinical application prospect in the prevention and treatment of CRS.

Background: Kidney transplantation constitutes the most effective therapeutic option for patients suffering from end-stage renal disease but remains burdened by a high incidence of cardiovascular disease. To date, exercise is an important preventive strategy that has been underestimated; in kidney transplant patients, exercise programs lead to an improvement in cardiorespiratory performance, muscle strength, arterial stiffness, and patients' quality of life perception.

Summary: The nephrology and transplant community have moved from generic suggestions to specific indications regarding frequency, intensity, time, type, volume, and progression of physical exercise both in the pre- and posttransplant phase. The latest guidelines from the World Health Organization for patients with chronic conditions propose a combination of aerobic, muscle-strengthening, and multicomponent exercises (e.g., balance) to improve health. Based on recent evidence, a combined exercise program (aerobic and strength exercise) is largely proposed to kidney transplant recipients. Aerobic exercise should be performed at an intensity >60% of theoretical maximum heart rate or maximum oxygen uptake possibly every day, and strength training should be performed at a >60% the estimate single maximum repetition, at least 2 times per week.

Key messages: Physical exercise should be personalized in relation to the patient's baseline performance; increases must be progressive and gradual. Regular physical activity should also be recommended to patients awaiting for a transplant. Eventually, organizational models based on a network of nephrology units, transplant centers, sports medicine centers, and fitness center or outdoor gym are essential elements for overcoming the logistical barriers for prescribing and carrying out regular physical activity.