Effects of high-fat diet on folic acid-induced kidney injury in mice.

Obesity is recognized as a significant contributor to the onset of kidney disease. However, the key processes involved in the development of kidney disease in obese individuals are not well understood. Here, we investigated the effects of high-fat diet (HFD)-induced obesity on folic acid (FA)-induced kidney injury in mice. Mice were fed an HFD for 12 weeks to induce obesity, followed by an additional intraperitoneal injection of FA. The results showed that mice fed HFD developed higher levels of kidney damage than those in the chow group. In contrast, mice exposed to both HFD and FA showed less fibrosis and inflammatory responses compared to the FA only treated group. Furthermore, the HFD with FA group exhibited elevated lipid accumulation in the kidney and reduced expression of mitochondrial proteins compared to the FA-treated group. Under in vitro experimental conditions, we found that lipid accumulation induced by oleic acid treatment reduced inflammatory and fibrotic responses in both renal tubules and fibroblasts. Finally, RNA sequencing analysis revealed that the inflammasome and pyroptosis signaling pathways were significantly increased in the HFD group with FA injection. In summary, these findings suggest that obesity increases renal injury due to a lack of appropriate inflammatory, fibrotic, and metabolic responses and the activation of the inflammasome and pyroptosis signaling pathways.

Renal Function and Its Impact on the Concentration of Ceftazidime-Avibactam: A cross-sectional study.

OBJECTIVES: This study measured the effect of renal function on the plasma concentrations of ceftazidime and avibactam in critically ill patients. We also sought to measure the concentration ratio of ceftazidime to avibactam. METHODS: This was a cohort study at a tertiary referral centre in Italy, on patients treated with continuous infusion of ceftazidime-avibactam (CAZ-AVI) between November 2019 and December 2023. The association between creatine clearance (CrCl) and free plasma ceftazidime and avibactam concentration, as well as CAZ-AVI ratio was explored to assess correlation and potential risk to fail to achieve target therapeutic concentration. RESULTS: 52 patients, predominantly male (75%), with a median age of 68.5 years were included. Our analyses provided strong evidence for inverse correlation between CrCl and both free-CAZ (r=-0.627; R2=0.3936; P<0.001) and free-AVI plasma concentration (r=-0.619; R2=0.3832; P<0.001). Overall CrCl alone could explain about 40% of overall variation of either free-CAZ and free-AVI. Linear models suggest that free-CAZ and free-AVI concentration drop of about 7.31% and 9.23% for each 10 point increase of CrCl, respectively. . Assessment of the CAZ-AVI ratio supports a direct linear association with CrCl suggesting that free-AVI concetration is more affected by CrCl variation than free-CAZ concentration. Patients with CrCl ≥130 mL/min showed a significantly higher risk of suboptimal drug exposure (i.e. less than 4 times the MIC) both to CAZ and AVI. CONCLUSION: The findings emphasize the need for individualized dosing strategies of CAZ-AVI based on renal function, for antibiotics used in critically ill patients. The study suggests that underdosing in patients with high CrCl is likely to be common and as such could affect drug effectiveness.

Chronic kidney diseases and inflammation research: a bibliometric analysis.

Background: Chronic kidney diseases (CKD) is a severe public health problem. This study aimed to explore the field of inflammation-related research in CKD from a bibliometric perspective. Methods: Relevant literature published between 2004 and 2023 were searched from the Web of Science database. The bibliometric analysis were performed to summarize countries, institutions, authors, journals and keywords using VOSviewer and CiteSpace. Results: A total of 9,287 publications on CKD and inflammation were included. Publications were mainly from the United States, China, Italy, Germany, and Japan. The findings revealed that the United States had the highest number of publications in this field, followed by China. There is strong collaboration between the two countries. The most productive institutions included the University of California system and the US Department of Veterans Affairs. Research hotspots primarily focused on inflammation mechanisms, biomarkers, and interventions. Conclusion: This study revealed the basic knowledge structure and provided a comprehensive insight into the research field of CKD and inflammation through bibliometric methods. Future studies should focus on early diagnosis, prevention, and treatment strategies of CKD, and explore more inflammation associated biomarkers and therapeutic targets for CKD.

Clinical glycoproteomics: methods and diseases.

Glycoproteins, representing a significant proportion of posttranslational products, play pivotal roles in various biological processes, such as signal transduction and immune response. Abnormal glycosylation may lead to structural and functional changes of glycoprotein, which is closely related to the occurrence and development of various diseases. Consequently, exploring protein glycosylation can shed light on the mechanisms behind disease manifestation and pave the way for innovative diagnostic and therapeutic strategies. Nonetheless, the study of clinical glycoproteomics is fraught with challenges due to the low abundance and intricate structures of glycosylation. Recent advancements in mass spectrometry-based clinical glycoproteomics have improved our ability to identify abnormal glycoproteins in clinical samples. In this review, we aim to provide a comprehensive overview of the foundational principles and recent advancements in clinical glycoproteomic methodologies and applications. Furthermore, we discussed the typical characteristics, underlying functions, and mechanisms of glycoproteins in various diseases, such as brain diseases, cardiovascular diseases, cancers, kidney diseases, and metabolic diseases. Additionally, we highlighted potential avenues for future development in clinical glycoproteomics. These insights provided in this review will enhance the comprehension of clinical glycoproteomic methods and diseases and promote the elucidation of pathogenesis and the discovery of novel diagnostic biomarkers and therapeutic targets.

Occupational risks associated with chronic kidney disease of non-traditional origin (CKDnt) in Brazil: it is time to dig deeper into a neglected problem / Riscos ocupacionais associados à doença renal crônica de origem não tradicional (DRCnt) no Brasil: é hora de nos aprofundarmos em um problema negligenciado

Abstract In the past decades, an epidemic of chronic kidney disease (CKD) has been associated with environmental and occupational factors (heat stress from high workloads in hot temperatures and exposure to chemicals, such as pesticides and metals), which has been termed CKD of non-traditional origin (CKDnt). This descriptive review aims to present recent evidence about heat stress, pesticides, and metals as possible causes of CKDnt and provide an overview of the related Brazilian regulation, enforcement, and health surveillance strategies. Brazilian workers are commonly exposed to extreme heat conditions and other CKDnt risk factors, including increasing exposure to pesticides and metals. Furthermore, there is a lack of adequate regulation (and enforcement), public policies, and strategies to protect the kidney health of workers, considering the main risk factors. CKDnt is likely to be a significant cause of CKD in Brazil, since CKD's etiology is unknown in many patients and several conditions for its development are present in the country. Further epidemiological studies may be conducted to explore causal associations and estimate the impact of heat, pesticides, and metals on CKDnt in Brazil. Moreover, public policies should prioritize reducing workers´ exposure and promoting their health and safety.

Resumo Nas últimas décadas, uma epidemia de doença renal crônica (DRC) tem sido associada a fatores ambientais e ocupacionais (estresse térmico decorrente de cargas de trabalho elevadas em altas temperaturas e exposição a produtos químicos, como agrotóxicos e metais), denominada DRC de origem não tradicional (DRCnt). Esta revisão descritiva tem como objetivo apresentar evidências recentes sobre estresse térmico, agrotóxicos e metais como possíveis causas de DRCnt e fornecer uma visão geral das estratégias brasileiras de regulamentação, fiscalização e vigilância sanitária relacionadas. Os trabalhadores brasileiros são comumente expostos a condições extremas de calor e outros fatores de risco de DRCnt, incluindo o aumento da exposição a agrotóxicos e metais. Além disso, há uma falta de regulamentação e fiscalização, políticas públicas e estratégias adequadas para proteger a saúde renal dos trabalhadores em relação aos principais fatores de risco. É provável que a DRCnt seja uma causa significativa de DRC no Brasil, uma vez que a etiologia da doença é desconhecida em muitos pacientes e diversas condições para seu desenvolvimento estão presentes no país. Estudos epidemiológicos devem ser realizados para explorar associações causais e estimar o impacto do calor, dos agrotóxicos e dos metais na DRCnt no Brasil. Além disso, as políticas públicas devem priorizar a redução da exposição dos trabalhadores e a promoção de sua saúde e segurança.

The significance of ferroptosis in renal diseases and its therapeutic potential.

Kidney diseases are significant global public health concern, with increasing prevalence and substantial economic impact. Developing novel therapeutic approaches are essential for delaying disease progression and improving patient quality of life. Cell death signifying the termination of cellular life, could facilitate appropriate bodily development and internal homeostasis. Recently, regulated cell death (RCD) forms such as ferroptosis, characterized by iron-dependent lipid peroxidation, has garnered attention in diverse renal diseases and other pathological conditions. This review offers a comprehensive examination of ferroptosis, encompassing an analysis of the involvement of iron and lipid metabolism, the System Xc - /glutathione/glutathione peroxidase 4 signaling, and additional associated pathways. Meanwhile, the review delves into the potential of targeting ferroptosis as a therapeutic approach in the management of acute kidney injury (AKI), chronic kidney disease (CKD), diabetic nephropathy, and renal tumors. Furthermore, it emphasizes the significance of ferroptosis in the transition from AKI to CKD and further accentuates the potential for repurposing drug and utilizing traditional medicine in targeting ferroptosis-related pathways for clinical applications. The integrated review provides valuable insights into the role of ferroptosis in kidney diseases and highlights the potential for targeting ferroptosis as a therapeutic strategy.

Targeted gene therapy for rare genetic kidney diseases.

Chronic kidney disease (CKD) is one of the leading causes of mortality worldwide because of kidney failure and the associated challenges of its treatment including dialysis and kidney transplantation. About one-third of CKD cases are linked to inherited monogenic factors, making them suitable for potential gene therapy interventions. However, the intricate anatomical structure of the kidney poses a challenge, limiting the effectiveness of targeted gene delivery to the renal system. In this review, we explore the progress made in the field of targeted gene therapy approaches and their implications for rare genetic kidney disorders, examining preclinical studies and prospects for clinical application. In vivo gene therapy is most commonly used for kidney-targeted gene delivery and involves administering viral and non-viral vectors through various routes such as systemic, renal vein and renal arterial injections. Small nucleic acids have also been used in preclinical and clinical studies for treating certain kidney disorders. Unexpectedly, hematopoietic stem and progenitor cells have been used as an ex vivo gene therapy vehicle for kidney gene delivery, highlighting their ability to differentiate into macrophages within the kidney, forming tunneling nanotubes that can deliver genetic material and organelles to adjacent kidney cells, even across the basement membrane to target the proximal tubular cells. As gene therapy technologies continue to advance and our understanding of kidney biology deepens, there is hope for patients with genetic kidney disorders to eventually avoid kidney transplantation.

Exploring the correlation between periodontal disease and serum biomarkers in haemodialysis patients.

BACKGROUND: Patients undergoing haemodialysis are more susceptible to infectious diseases, including periodontitis. This study aimed to investigate the Correlation between periodontal disease and serum markers in Yemeni haemodialysis patients. METHODS: A cross-sectional study was conducted on a sample of 70 haemodialysis patients. Patient interviews, clinical examinations, and laboratory tests were performed to collect data. Serum levels of albumin, calcium, phosphorus, haemoglobin, ferritin, and creatinine were measured, with separate measurements for cystatin C The association between categorical variables was assessed using the chi-square test and Pearson's correlation coefficient, considering a significance level of p < 0.05. RESULTS: Significant correlations were found between serum biomarkers and periodontal clinical parameters. Phosphorus, creatinine, albumin, ferritin, and creatinine levels correlated significantly with the Plaque Index (p < 0.001, p < 0.001, p = 0.015, p = 0.018, and p = 0.03). While the Ferritin level showed significant correlations with both the Plaque Index and Miller Classes (r = 0.281, p = 0.018 and r = 0.258, p = 0.031), respectively. The Calcium level showed a significant correlation with the Gingival Index (r = 0.266, p = 0.027). Cystatin C level was statistically correlated with mobility (r = 0.258, p = 0.031). Also, the result showed a significant correlation between Creatinine levels and Periodontitis (r = 0.26, p = 0.03). CONCLUSION: This study provides evidence of a strong association between periodontal disease and chronic kidney disease in Yemeni haemodialysis patients. The findings emphasize the significance of maintaining good oral health in the care of haemodialysis patients.

Evaluation and Management of Kidney Dysfunction in Advanced Heart Failure: A Scientific Statement From the American Heart Association.

Early identification of kidney dysfunction in patients with advanced heart failure is crucial for timely interventions. In addition to elevations in serum creatinine, kidney dysfunction encompasses inadequate maintenance of sodium and volume homeostasis, retention of uremic solutes, and disrupted endocrine functions. Hemodynamic derangements and maladaptive neurohormonal upregulations contribute to fluctuations in kidney indices and electrolytes that may recover with guideline-directed medical therapy. Quantifying the extent of underlying irreversible intrinsic kidney disease is crucial in predicting whether optimization of congestion and guideline-directed medical therapy can stabilize kidney function. This scientific statement focuses on clinical management of patients experiencing kidney dysfunction through the trajectory of advanced heart failure, with specific focus on (1) the conceptual framework for appropriate evaluation of kidney dysfunction within the context of clinical trajectories in advanced heart failure, including in the consideration of advanced heart failure therapies; (2) preoperative, perioperative, and postoperative approaches to evaluation and management of kidney disease for advanced surgical therapies (durable left ventricular assist device/heart transplantation) and kidney replacement therapies; and (3) the key concepts in palliative care and decision-making processes unique to individuals with concomitant advanced heart failure and kidney disease.

The multifaceted effects of mitochondria in kidney diseases.

Mitochondria serve as the primary site for aerobic respiration within cells, playing a crucial role in maintaining cellular homeostasis. To maintain homeostasis and meet the diverse demands of the cells, mitochondria have evolved intricate systems of quality control, mainly including mitochondrial dynamics, mitochondrial autophagy (mitophagy) and mitochondrial biogenesis. The kidney, characterized by its high energy requirements, is particularly abundant in mitochondria. Interestingly, the mitochondria display complex behaviors and functions. When the kidney is suffered from obstructive, ischemic, hypoxic, oxidative, or metabolic insults, the dysfunctional mitochondrial derived from the defects in the mitochondrial quality control system contribute to cellular inflammation, cellular senescence, and cell death, posing a threat to the kidney. However, in addition to causing injury to the kidney in several cases, mitochondria also exhibit protective effect on the kidney. In recent years, accumulating evidence indicated that mitochondria play a crucial role in adaptive repair following kidney diseases caused by various etiologies. In this article, we comprehensively reviewed the current understanding about the multifaceted effects of mitochondria on kidney diseases and their therapeutic potential.

Predictors of acute kidney injury in dengue patients: a systematic review and meta-analysis.

BACKGROUND: Dengue infection poses a significant global health challenge, particularly in tropical and subtropical regions. Among its severe complications, Acute kidney injury (AKI) stands out due to its association with increased morbidity, mortality, and healthcare burdens. This Meta-analysis aim to identify and evaluate the predictors of AKI among dengue patients, facilitating early detection and management strategies to mitigate AKI's impact. METHODS: We searched PubMed, EMBASE, and Web of Science databases, covering literature up to February 2024. We included human observational studies reporting on AKI predictors in confirmed dengue cases. Nested-Knowledge software was used for screening and data extraction. The Newcastle-Ottawa Scale was used for quality assessment. R software (V 4.3) was utilized to compute pooled odds ratios (ORs) and 95% confidence intervals (CIs) for each predictor. RESULTS: Our search yielded nine studies involving diverse geographic locations and patient demographics. A total of 9,198 patients were included in the studies, with 542 diagnosed with AKI. in which key predictors of AKI identified include severe forms of dengue (OR: 2.22, 95% CI: 1.02-3.42), male gender (OR: 3.13, 95% CI: 1.82-4.44), comorbidities such as diabetes mellitus (OR: 3.298, 95% CI: 0.274-6.322), and chronic kidney disease (OR: 2.2, 95% CI: 0.42-11.24), as well as co-infections and clinical manifestations like rhabdomyolysis and major bleeding. CONCLUSION: Our study identifies several predictors of AKI in dengue patients. These findings indicate the importance of early identification and intervention for high-risk individuals. Future research should focus on standardizing AKI diagnostic criteria within the dengue context and exploring the mechanisms underlying these associations to improve patient care and outcomes.

PARVB deficiency alleviates cisplatin-induced tubular injury by inhibiting TAK1 signaling.

Cisplatin-induced renal tubular injury largely restricts the wide-spread usage of cisplatin in the treatment of malignancies. Identifying the key signaling pathways that regulate cisplatin-induced renal tubular injury is thus clinically important. PARVB, a focal adhesion protein, plays a crucial role in tumorigenesis. However, the function of PARVB in kidney disease is largely unknown. To investigate whether and how PARVB contributes to cisplatin-induced renal tubular injury, a mouse model (PARVB cKO) was generated in which PARVB gene was specifically deleted from proximal tubular epithelial cells using the Cre-LoxP system. In this study, we found depletion of PARVB in proximal tubular epithelial cells significantly attenuates cisplatin-induced renal tubular injury, including tubular cell death and inflammation. Mechanistically, PARVB associates with transforming growth factor-ß-activated kinase 1 (TAK1), a central regulator of cell survival and inflammation that is critically involved in mediating cisplatin-induced renal tubular injury. Depletion of PARVB promotes cisplatin-induced TAK1 degradation, inhibits TAK1 downstream signaling, and ultimately alleviates cisplatin-induced tubular cell damage. Restoration of PARVB or TAK1 in PARVB-deficient cells aggravates cisplatin-induced tubular cell injury. Finally, we demonstrated that PARVB regulates TAK1 protein expression through an E3 ligase ITCH-dependent pathway. PARVB prevents ITCH association with TAK1 to block its ubiquitination. Our study reveals that PARVB deficiency protects against cisplatin-induced tubular injury through regulation of TAK1 signaling and indicates targeting this pathway may provide a novel therapeutic strategy to alleviate cisplatin-induced kidney damage.

Mendelian randomization analyses explore the effects of micronutrients on different kidney diseases.

Background: The impact of micronutrients, including vitamins and minerals, on different kidney diseases has been reported in some observational studies; however, their causal relationship remains uncertain. We aimed to ascertain the causal genetic relationships between micronutrients and different kidney diseases using the Mendelian randomization (MR) method. Methods: Instrumental variables (IVs) for genetically predicting calcium (Ca), iron (Ir), Zinc (Zn), selenium (Se), copper (Cu), vitamin D (Vit D), and vitamin C (Vit C) levels in humans were obtained, and a bidirectional two-sample MR was used to examine potential associations between the levels of these seven micronutrients and the risk of seven different kidney diseases including hypertensive renal disease, diabetic nephropathy, IgA nephropathy, membranous nephropathy, cystic nephropathy, chronic kidney disease (CKD), and chronic tubulo-interstitial nephritis. Five different MR analyses were conducted, with the main method being the inverse variance-weighted (IVW) method. Moreover, sensitivity analyses were performed to assess heterogeneity and potential pleiotropy. Results: The IVW method revealed that Ca levels were associated with a decreased risk of hypertensive renal disease (OR = 0.61, 95% CI: 0.40-0.93, p-value = 0.022), and Se levels were associated with a decreased risk of hypertensive renal disease (OR = 0.72, 95% CI: 0.53-0.99, p-value = 0.040), diabetic nephropathy (OR = 0.83, 95% CI: 0.73-0.93, p-value = 0.002), and CKD (OR = 0.87, 95% CI: 0.77-0.99, p-value = 0.028). Conversely, Vit D levels were associated with an increased risk of polycystic kidney disease (OR = 1.76, 95% CI: 1.15-2.69, p-value = 0.0095). In addition, no potential causal relationship was found between vitamin C levels, iron levels, zinc levels, and copper levels and different kidney diseases. Meanwhile, inverse Mendelian randomization showed no potential causal relationship between different chronic kidney diseases and micronutrients. The Cochrane's Q test, MR-Egger regression, and MR-PRESSO did not suggest heterogeneity and pleiotropy, providing evidence of the validity of the MR estimates. Conclusion: Our results indicate a cause-and-effect connection between micronutrients and certain kidney diseases, but additional study is required to provide more conclusive evidence. This research has the potential to assist clinicians in managing the consumption of specific micronutrients among individuals with chronic kidney diseases, as well as in promoting disease prevention among both healthy populations and those who are susceptible to chronic underlying conditions.

Postmenopausal status increases the risk of uric acid stones.

OBJECTIVE: This study investigated the impact of menopause on stone composition in women with urolithiasis. STUDY DESIGN: A cross-sectional study was conducted from March 2013 to March 2018. Women with urolithiasis patients were divided into two groups according to their menopause status. MAIN OUTCOME MEASURES: The clinical demographic characteristics, stone removal, stone composition, and urine chemistry were investigated. Univariate and multivariate survival analyses were performed to identify risk factors for the risk of uric acid stones. RESULTS: Our study enrolled 1221 female patients with stone diseases, 783 (64.1 %) of whom were postmenopausal (66 patients surgically menopause and 717 patients naturally menopause). Postmenopausal women had higher rates of diabetes and hyperuricemia, a higher serum uric acid level, a higher urinary specific gravity, and a lower estimated glomerular filtration rate. Stone analysis revealed calcium oxalate stones in 66.2 % of the patients, apatite stones in 19.4 %, calcium oxalate and calcium phosphate stones in 7.7 %, uric acid stones in 4.4 %, struvite stones in 2.0 %, and brushite stones in 0.2 %. Postmenopausal women had a higher rate of uric acid stones. Multivariate analysis confirmed that postmenopausal status and hyperuricemia were independent risk factors of uric acid stones. Postmenopausal women required more invasive procedures to remove the stones, and they had lower self-voiding rates. CONCLUSIONS: Postmenopausal women had higher rates of stone episodes, specifically related to uric acid stones. Given the prevalence and impact of chronic kidney diseases, factors that impede optimal renal function management in women must be identified to provide tailored treatment recommendations.

Usefulness and caveats of real-world data for research on hypertension and its association with cardiovascular or renal disease in Japan.

The role of real-world data, collected from clinical practice rather than clinical trials, has become increasingly important for investigating real-life situations, such as treatment effects. In Japan, evidence on hypertension, cardiovascular diseases, and kidney diseases using real-world data is increasing. These studies are mainly based on "the insurer-based real-world data" collected as electronic records, including data from health check-ups and medical claims such as JMDC database, DeSC database, the Japan Health Insurance Association (JHIA) database, or National Databases of Health Insurance Claims and Specific Health Checkups (NDB). Based on the insurer-based real-world data, traditional but finely stratified associations between hypertension and cardiovascular or kidney diseases can be explored. The insurer-based real-world data are also useful for pharmacoepidemiological studies that capture the distribution and trends of drug prescriptions; combined with annual health check-up data, the effectiveness of drugs can also be examined. Despite the usefulness of insurer-based real-world data collected as electronic records from a wide range of populations, we must be cautious about several points, including issues regarding population uncertainty, the validity of cardiovascular outcomes, the accuracy of blood pressure, traceability, and biases, such as indication and immortal biases. While a large sample size is considered a strength of real-world data, we must keep in mind that it does not overcome the problem of systematic error. This review discusses the usefulness and pitfalls of insurer-based real-world data in Japan through recent examples of Japanese research on hypertension and its association with cardiovascular or kidney disease.

Role of Magnesium, Effects of Hypomagnesemia, and Benefits of Magnesium Supplements in Cardiovascular and Chronic Kidney Diseases.

Cardiovascular diseases (CVDs) account for nearly half of chronic kidney disease (CKD)-related deaths. Hypomagnesemia has been associated with various cardiovascular conditions and predicts a decline in renal function leading to end-stage renal disease (ESRD). The objective of this review is to delve into and discuss the significance of magnesium (Mg) in cardiovascular and renal functions, the clinical consequences of hypomagnesemia on CVD and CKD, and the benefits of Mg supplementation in managing CVD and CKD. This review is the result of an extensive search for pertinent articles in databases like PubMed, Medline, PubMed Central, and Google Scholar. Based on the literature search conducted in this review, we concluded that Mg protects against various CVDs and delays the progression of CKD. Mg can regulate pathways associated with inflammation, oxidative stress, and fibrosis. Therefore, maintaining slightly elevated Mg levels and timely Mg supplementation may benefit patients with CVD and CKD. There is a need for additional prospective randomized controlled trials to fully comprehend the therapeutic effects of Mg on CVD and CKD along with setting individualized target levels for serum Mg in such patients.

Assessment of the causal relationship between inflammatory bowel diseases and chronic kidney diseases: A two-sample bidirectional mendelian randomization study among European population.

BACKGROUND: Kidney function can be impaired in patients with inflammatory bowel diseases (IBD), including Crohn's diseases (CD) and ulcerative colitis (UC). However, the causal relationship between IBD and chronic kidney diseases (CKD) remains unclear. METHODS: We determined the causal association between IBD and CKD by performing two-sample bidirectional mendelian randomization (MR) analyses. Independent genetic variants were selected as instrumental variables (IVs) of the exposure from open-access genome-wide association studies (GWAS) among European ancestry. IVs-outcome estimates were extracted from three separate GWAS for IBD and two for CKD, respectively. Inverse-variance-weighted model was used as the primary MR method. The pleiotropic effect and heterogeneity were evaluated. For either direction, analyses were performed per outcome database and were subsequently meta-analysed. RESULTS: Genetically predicted IBD was associated with higher risk of CKD (OR: 1.045, 95% CI: 1.016-1.073, P = 0.002) by including 42 344 IBD cases and 229 164 controls. Further analyses showed genetic liability to CD increased the risk of CKD (OR: 1.057, 95% CI: 1.027-1.087, p < 0.001) whereas UC did not (OR: 0.999, 95% CI:0.969-1.031, p = 0.970). In contrast, genetically predicted CKD was not associated with IBD (OR: 1.010, 95% CI: 0.965-1.056, p = 0.676), UC (OR: 1.011, 95% CI: 0.948-1.078, p = 0.746) and CD (OR: 1.024; 95% CI: 0.963-1.089, p = 0.447). CONCLUSIONS: We concluded that CD, but not UC, can increase the risk of CKD causally. CD, but not UC, can increase the risk of chronic kidney disease causally. These findings enhance our understanding of the differential impact of IBD subtypes on CKD. It may be necessary to monitor kidney function regularly in patients with CD.

microRNAs in kidney diseases: Regulation, therapeutics, and biomarker potential.

MicroRNAs (miRNAs) are small, non-coding RNA molecules that play a crucial role in regulating gene expression by inhibiting the translation of their specific target messenger RNAs. To date, numerous studies have demonstrated changes in the expression of miRNAs in the kidneys throughout the progression of both acute kidney injury (AKI) and chronic kidney disease (CKD) in both human patients and experimental models. The role of specific microRNAs in the pathogenesis of kidney diseases has also been demonstrated. Further studies have elucidated the regulation of these microRNAs in diseased kidneys. Besides, certain miRNAs are detected in plasma and/or urine in kidney diseases and are potential diagnostic biomarkers. In this review, we provide an overview of recent developments in our understanding of how miRNAs contribute to kidney diseases. We also explore the potential of miRNAs as both biomarkers and therapeutic targets for these conditions, and highlight future research directions.

Differences in palliative care needs between cancer patients and non-cancer patients at the start of specialized palliative care: A nationwide register-based study.

BACKGROUND: Patients with non-cancer disease are less likely to receive specialized palliative care than cancer patients. To be able to provide the best specialized palliative care, it is important to understand palliative care needs of non-cancer patients and whether the type and level of needs differ from those of cancer patients. Large studies including both cancer and non-cancer patients, using validated needs-assessment-tools, are needed to understand differences in palliative care needs at admittance to specialized palliative care. AIMS: To compare palliative care needs at the start of palliative care for cancer and non-cancer disease. DESIGN: Six-year nationwide register-based study. SETTING/PARTICIPANTS: This study included patients from all Danish specialized palliative care services (hospice care, hospital-based palliative care, home-based palliative care, or consultation) who completed a need-assessment-questionnaire. Ordinal logistic regression was performed to study the association between diagnosis and needs. RESULTS: Cancer patients had a higher probability of receiving specialized palliative care. Of the 44,315 palliative care admissions included in this study, 93.3% were on cancer patients. Independent of diagnosis patients experienced on average six needs and high levels of fatigue and impaired physical functioning. Non-cancer patients had significantly higher odds of insomnia, fatigue and impaired emotional functioning, physical functioning, and quality of life whereas cancer patients had higher odds of pain (except for patients with neurological disease). CONCLUSIONS: The higher levels of several symptoms/problems among non-cancer patients compared to cancer patients suggests that referral to specialized palliative care should be improved for non-cancer patients perhaps by improving identification of palliative needs.