Cope with copper: From molecular mechanisms of cuproptosis to copper-related kidney diseases.

Cuproptosis has recently been identified as a novel regulatory mechanism of cell death. It is characterized by the accumulation of copper in mitochondria and its binding to acylated proteins. These characteristics lead to the downregulation of iron-sulfur cluster proteins and protein toxicity stress, ultimately resulting in cell death. Cuproptosis is distinct from other types of cell death, including necrosis, apoptosis, ferroptosis, and pyroptosis. Cu induces oxidative stress damage, protein acylation, and the oligomerization of acylated TCA cycle proteins. These processes lead to the downregulation of iron-sulfur cluster proteins and protein toxicity stress, disrupting cellular Cu homeostasis, and causing cell death. Cuproptosis plays a significant role in the development and progression of various kidney diseases such as acute kidney injury, chronic kidney disease, diabetic nephropathy, kidney transplantation, and kidney stones. On the one hand, inducers of cuproptosis, such as disulfiram (DSF), chloroquinolone, and elesclomol facilitate cuproptosis by promoting cell oxidative stress. In contrast, inhibitors of Cu chelators, such as tetraethylenepentamine and tetrathiomolybdate, relieve these diseases by inhibiting apoptosis. To summarize, cuproptosis plays a significant role in the pathogenesis of kidney disease. This review comprehensively discusses the molecular mechanisms underlying cuproptosis and its significance in kidney diseases.

[Quantification of the burden of chronic kidney disease in Latin America: an invisible epidemicQuantificação da carga da doença renal crônica na América Latina: uma epidemia invisível]. / Cuantificación de la carga de la enfermedad renal crónica en América Latina: una epidemia invisibilizada.

Objective: 1) Describe the burden of chronic kidney disease in Latin American countries between 1990 and 2019; and 2) Estimate the correlation between disability-adjusted life years (DALYs) and the Sociodemographic Index and the Healthcare Access and Quality Index. Methods: Secondary and ecological analysis, based on the 2019 Global Burden of Diseases, Injuries and Risk Factors Study. Standardized mortality rates, years of life lost to due to premature death (YLLs),years of healthy life lost due to disability (YLDs) and DALYs due to chronic kidney disease were reported for 1990, 2005, and 2019. Information was disaggregated by country, sex, age group, and sub-cause. Results: Between 1990 and 2019, the burden of chronic kidney disease increased considerably in Latin American countries, becoming one of the main causes of mortality and DALYs. The standardized rate of DALYs for chronic kidney disease was largely due to the weight of premature deaths rather than disability. In 2019, Nicaragua, El Salvador, Mexico, and Guatemala had the highest standardized mortality rates for chronic kidney disease and DALYs, while Uruguay had the lowest. Conclusions: Chronic kidney disease is an invisible epidemic that places an excessive burden in terms of mortality and DALYs on Latin American countries. It is essential to join forces to tackle the disease in the region, and promote local actions that address the particularities of each country.

Objetivo: 1) Descrever a carga da doença renal crônica nos países da América Latina entre 1990 e 2019 e 2) estimar a correlação entre os anos de vida saudável perdidos (AVISA), o índice sociodemográfico e o índice de acesso e qualidade da saúde. Métodos: Análise secundária e ecológica, baseada no estudo Carga Global de Doenças, Lesões e Fatores de Risco 2019 (GBD). Foram informadas taxas de mortalidade padronizadas, anos de vida perdidos por morte prematura (AVP) por morte prematura, anos de vida ajustados por incapacidade (AVAI) e AVISA devido a doença renal crônica de 1990, 2005 e 2019. Os dados foram desagregados por país, sexo, faixas etárias e causas subjacentes. Resultados: Entre 1990 e 2019, a carga de doença renal crônica aumentou consideravelmente nos países da América Latina, tornando-se uma das principais causas de mortalidade e de AVISA. A taxa padronizada de AVISA devido à doença renal crônica foi influenciada em grande parte pelo peso das mortes prematuras, e não da incapacidade. Em 2019, Nicarágua, El Salvador, México e Guatemala se destacaram por terem as maiores taxas padronizadas de mortalidade por doença renal crônica e AVISA, ao passo que Uruguai teve as menores taxas. Conclusões: A doença renal crônica é uma epidemia invisível, que representa uma carga excessiva em termos de mortalidade e de AVISA para os países da América Latina. É essencial unir esforços na região para combater a doença, além de promover ações locais que atendam às particularidades de cada país.

Evaluating ChatGPT's efficacy in assessing the safety of non-prescription medications and supplements in patients with kidney disease.

Background: This study investigated the efficacy of ChatGPT-3.5 and ChatGPT-4 in assessing drug safety for patients with kidney diseases, comparing their performance to Micromedex, a well-established drug information source. Despite the perception of non-prescription medications and supplements as safe, risks exist, especially for those with kidney issues. The study's goal was to evaluate ChatGPT's versions for their potential in clinical decision-making regarding kidney disease patients. Method: The research involved analyzing 124 common non-prescription medications and supplements using ChatGPT-3.5 and ChatGPT-4 with queries about their safety for people with kidney disease. The AI responses were categorized as "generally safe," "potentially harmful," or "unknown toxicity." Simultaneously, these medications and supplements were assessed in Micromedex using similar categories, allowing for a comparison of the concordance between the two resources. Results: Micromedex identified 85 (68.5%) medications as generally safe, 35 (28.2%) as potentially harmful, and 4 (3.2%) of unknown toxicity. ChatGPT-3.5 identified 89 (71.8%) as generally safe, 11 (8.9%) as potentially harmful, and 24 (19.3%) of unknown toxicity. GPT-4 identified 82 (66.1%) as generally safe, 29 (23.4%) as potentially harmful, and 13 (10.5%) of unknown toxicity. The overall agreement between Micromedex and ChatGPT-3.5 was 64.5% and ChatGPT-4 demonstrated a higher agreement at 81.4%. Notably, ChatGPT-3.5's suboptimal performance was primarily influenced by a lower concordance rate among supplements, standing at 60.3%. This discrepancy could be attributed to the limited data on supplements within ChatGPT-3.5, with supplements constituting 80% of medications identified as unknown. Conclusion: ChatGPT's capabilities in evaluating the safety of non-prescription drugs and supplements for kidney disease patients are modest compared to established drug information resources. Neither ChatGPT-3.5 nor ChatGPT-4 can be currently recommended as reliable drug information sources for this demographic. The results highlight the need for further improvements in the model's accuracy and reliability in the medical domain.

A multi-hierarchical approach reveals d-serine as a hidden substrate of sodium-coupled monocarboxylate transporters.

Transporter research primarily relies on the canonical substrates of well-established transporters. This approach has limitations when studying transporters for the low-abundant micromolecules, such as micronutrients, and may not reveal physiological functions of the transporters. While d-serine, a trace enantiomer of serine in the circulation, was discovered as an emerging biomarker of kidney function, its transport mechanisms in the periphery remain unknown. Here, using a multi-hierarchical approach from body fluids to molecules, combining multi-omics, cell-free synthetic biochemistry, and ex vivo transport analyses, we have identified two types of renal d-serine transport systems. We revealed that the small amino acid transporter ASCT2 serves as a d-serine transporter previously uncharacterized in the kidney and discovered d-serine as a non-canonical substrate of the sodium-coupled monocarboxylate transporters (SMCTs). These two systems are physiologically complementary, but ASCT2 dominates the role in the pathological condition. Our findings not only shed light on renal d-serine transport, but also clarify the importance of non-canonical substrate transport. This study provides a framework for investigating multiple transport systems of various trace micromolecules under physiological conditions and in multifactorial diseases.

Role of Doppler Evaluation in Assessing the Maturation of the Arteriovenous Fistula for Hemodialysis: An Observational Study.

Introduction Arteriovenous fistulas (AVFs) are the preferred type of vascular access for hemodialysis due to their lower risk of complications. This study aimed to determine the role of Doppler evaluation in assessing AVF. Materials and methods We conducted an 18-month prospective observational study of 33 hemodialysis patients who underwent a procedure for the creation of AVF at the Department of Radio-Diagnosis at Sri Devaraj Urs Academy of Higher Education and Research. Patients were evaluated using color Doppler ultrasound. Participants underwent a careful history and clinical examination to diagnose the disease. All relevant parameters were documented in a structured study proforma. AVF maturation was assessed postoperatively at four weeks using Doppler ultrasound color flow evaluation by looking for vascular components (flow volume, vein, and arterial diameter). Data were analyzed using CoGuide V 1.0.3 Statistical Software (CoGuide, Bangalore, India). Results A total of 33 patients, with a mean age of 54.6 ± 7.8 years, were evaluated. Of the 33 participants, 24 (72.7%) were male, and nine (27.3%) were female. The majority (47%, n=16) of participants had diabetes mellitus, eight (24%) had hypertension, and 10 (29%) had both diabetes mellitus and hypertension. A brachiocephalic fistula was created in 45.5% of participants, and 33.33% had radiocephalic anastomoses. Five participants were diagnosed with AVF complications: two had a pseudoaneurysm, and three had a cephalic vein thrombus. Clinical and demographic characteristics (age, vascular components, and complications) were not significantly related to AVF maturation. Conclusions Doppler ultrasound plays an important role in selecting vessels for AVF preoperatively and assessing AVF maturation postoperatively, thus reducing the primary fistula failure rate. The findings suggest that Doppler evaluation can be a reliable tool for assessing AVF maturation and predicting surgical success, which could help healthcare providers make informed decisions about the best course of treatment for their patients. Continued research is warranted in this area to further understand the role of Doppler ultrasound in evaluating AVF surgery.

Associations of urinary fetuin-A with histopathology and kidney events in biopsy-proven kidney disease.

Background: Fetuin-A is implicated in the pathogenesis of vascular calcification in chronic kidney disease (CKD); however, the relationship between fetuin-A, histopathologic lesions and long-term kidney outcomes in patients with various types of kidney disease remains unclear. Methods: We measured urinary fetuin-A levels in 335 individuals undergoing clinically indicated native kidney biopsy. The expressions of fetuin-A mRNA and protein in the kidney were assessed using RNA sequencing and immunohistochemistry. The association of urinary fetuin-A with histopathologic lesions and major adverse kidney events (MAKE), defined as a decline in estimated glomerular filtration rate (eGFR) of at least 40%, kidney failure or death, was analyzed. Results: Urinary fetuin-A levels showed a positive correlation with albuminuria (rs = 0.67, P < .001) and a negative correlation with eGFR (rs = -0.46, P < .001). After multivariate adjustment, higher urinary fetuin-A levels were associated with glomerular inflammation, mesangial expansion, interstitial fibrosis and tubular atrophy, and arteriolar sclerosis. Using a 1 transcript per million gene expression cutoff, we found kidney fetuin-A mRNA levels below the threshold in both individuals with normal kidney function and those with CKD. Additionally, immunohistochemistry revealed reduced fetuin-A staining in tubular cells of CKD patients compared with normal controls. During a median 21-month follow-up, 115 patients experienced MAKE, and Cox regression analysis confirmed a significant association between elevated urinary fetuin-A and MAKE. This association remained significant after adjusting for potential confounding factors. Conclusion: Urinary fetuin-A is associated with chronic histological damage and adverse clinical outcomes across a spectrum of biopsy-proven kidney diseases.

Calcium signaling induces partial EMT and renal fibrosis in a Wnt4mCherry knock-in mouse model.

The renal tubular epithelial cells (TEC) have a strong capacity for repair after acute injury, but when this mechanism becomes uncontrollable, it leads to chronic kidney diseases (CKD). Indeed, in progress toward CKDs, the TECs may dedifferentiate, undergo epithelial-to-mesenchyme transition (EMT), and promote inflammation and fibrosis. Given the critical role of Wnt4 signaling in kidney ontogenesis, we addressed whether changes in this signaling are connected to renal inflammation and fibrosis by taking advantage of a knock-in Wnt4mCh/mCh mouse. While the Wnt4mCh/mCh embryos appeared normal, the corresponding mice, within one month, developed CKD-related phenotypes, such as pro-inflammatory responses including T-cell/macrophage influx, expression of fibrotic markers, and epithelial cell damage with a partial EMT. The Wnt signal transduction component ß-catenin remained unchanged, while calcium signaling is induced in the injured TECs involving Nfat and Tfeb transcription factors. We propose that the Wnt4 signaling pathway is involved in repairing the renal injury, and when the signal is overdriven, CKD is established.

Inhibition of HDAC6 with CAY10603 alleviates acute and chronic kidney injury by suppressing the ATF6 branch of UPR.

BACKGROUND: Histone deacetylase 6 (HDAC6) inhibitor CAY10603 has been identified as a potential therapeutic agent for the treatment of diabetic kidney disease (DKD). The objective of this study was to investigate the therapeutic effects of CAY10603 in mice with acute kidney injury (AKI) and chronic kidney diseases (CKD). METHODS: Renal immunohistology was performed to assess the expression levels of HDAC6 in both human and mouse kidney samples. C57BL/6J mice were intraperitoneal injected with lipopolysaccharide (LPS) to induce AKI; CD-1 mice were fed with adenine diet to induce adenine-nephropathy as CKD model. Serum creatinine, blood urea nitrogen and uric acid were measured to reflect renal function; renal histology was applied to assess kidney damage. Western blot and immunohistology were used to analyze the unfolded protein response (UPR) level. RESULTS: HDAC6 was significantly upregulated in renal tubular epithelial cells (RTECs) of both AKI and CKD patients as well as mice. In the murine models of AKI induced by LPS and adenine-induced nephropathy, CAY10603 exhibited notable protective effects, including improvement in biochemical indices and pathological changes. In vivo and in vitro studies revealed that CAY10603 effectively suppressed the activation of activating transcription factor 6 (ATF6) branch of UPR triggered by thapsigargin (Tg), a commonly employed endoplasmic reticulum (ER) stressor. Consistent with these findings, CAY10603 also displayed substantial inhibition of ATF6 activation in RTECs from both murine models of LPS-induced AKI and adenine-induced nephropathy. CONCLUSIONS: Collectively, these results suggest that CAY10603 holds promise as a potential therapeutic agent for both acute and chronic kidney injury.

Glomerulonephritis following COVID-19 infection or vaccination: a multicenter study in South Korea.

BACKGROUND: Despite the widespread impact of the severe acute respiratory syndrome coronavirus 2 (coronavirus disease 2019, COVID-19) and vaccination in South Korea, our understanding of kidney diseases following these events remains limited. We aimed to address this gap by investigating the characteristics of glomerular diseases following the COVID-19 infection and vaccination in South Korea. METHODS: Data from multiple centers were used to identify de novo glomerulonephritis (GN) cases with suspected onset following COVID-19 infection or vaccination. Retrospective surveys were used to determine the COVID-19-related histories of patients who were initially not implicated. Bayesian structural time series and autoregressive integrated moving average models were used to determine causality. RESULTS: Glomerular diseases occurred shortly after the infection or vaccination. The most prevalent postinfection GN was podocytopathy (42.9%), comprising primary focal segmental glomerulosclerosis and minimal change disease, whereas postvaccination GN mainly included immunoglobulin A nephropathy (IgAN; 57.9%) and Henoch-Schönlein purpura nephritis (HSP; 15.8%). No patient progressed to end-stage kidney disease. Among the patients who were initially not implicated, nine patients with IgAN/HSP were recently vaccinated against COVID-19. The proportion of glomerular diseases changed during the pandemic in South Korea, with an increase in acute interstitial nephritis and a decrease in pauci-immune crescentic GN. CONCLUSION: This study showed the characteristics of GNs following COVID-19 infection or vaccination in South Korea. Understanding these associations is crucial for developing effective patient management and vaccination strategies. Further investigation is required to fully comprehend COVID-19's impact on GN.

EXPRESS: Clinical Outcomes and Clinico-Pathological Correlations in Children with MPO-ANCA-Associated Glomerulonephritis Showing Renal Arteritis.

OBJECTIVE: The aim of this study was to evaluate the clinical features, pathological characteristics and prognosis in myeloperoxidase (MPO)-antineutrophil cytoplasmic antibodies-associated glomerulonephritis (AAGN) with renal arteritis. METHODS: The study involved 97 children from five pediatric clinical centers with MPO-AAGN who exhibited distinct clinical features. The patients were divided into AAGN-A+ and AAGN-A-, based on the presence or absence of arteritis, and the disparities in clinical, histopathological characteristics, and prognosis between the two groups were evaluated. RESULT: In contrast to the AAGN-A- group, the children in the AAGN-A+ group exhibited more pronounced clinical symptoms and renal pathological injury. Arteritis positively moderately correlated with the serum creatinine (Scr), IL-6 (interleukin-6), urinary neutrophil gelatinase-associated lipocalin (NGAL), negatively moderately correlated with serum complement C3. The renal survival rate in the AAGN-A+ group was significantly poorer than AAGN-A- group (χ2=4.278, P=0.039). Arteritis showed a good predictive value for end-stage kidney disease (ESKD), and C3 deposition and arteritis were independent risk factors for the development of ESKD in children with MPO-AAGN. CONCLUSION: Arteritis is a significant pathological change observed in children with MPO-AAGN, and the formation of arteritis may be related to the inflammatory response and activation of the complement system.

Prevention and treatment of ischaemic and haemorrhagic stroke in people with diabetes mellitus: a focus on glucose control and comorbidities.

Diabetes mellitus is a significant risk factor for both ischaemic and haemorrhagic stroke, affecting up to a third of individuals with cerebrovascular diseases. Beyond being a risk factor for stroke, diabetes and hyperglycaemia have a negative impact on outcomes after ischaemic and haemorrhagic stroke. Hyperglycaemia during the acute ischaemic stroke phase is associated with a higher risk of haemorrhagic transformation and poor functional outcome, with evidence in favour of early intervention to limit and manage severe hyperglycaemia. Similarly, intensive glucose control nested in a broader bundle of care, including blood pressure, coagulation and temperature control, can provide substantial benefit for clinical outcomes after haemorrhagic stroke. As micro- and macrovascular complications are frequent in people with diabetes, cardiovascular prevention strategies also need to consider tailored treatment. In this regard, the broader availability of sodium-glucose cotransporter 2 inhibitors and glucagon-like peptide 1 receptor agonists can allow tailored treatments, particularly for those with heart failure and chronic kidney disease as comorbidities. Here, we review the main concepts of hyperacute stroke management and CVD prevention among people with diabetes, capitalising on results from large studies and RCTs to inform clinicians on preferred treatments.

Engineered Extracellular Vesicles in Chronic Kidney Diseases: A Comprehensive Review.

Chronic kidney diseases (CKD) present a formidable global health challenge, characterized by a deficiency of effective treatment options. Extracellular vesicles (EVs), recognized as multifunctional drug delivery systems in biomedicine, have gained accumulative interest. Specifically, engineered EVs have emerged as a promising therapeutic approach for targeted drug delivery, potentially addressing the complexities of CKD management. In this review, we systematically dissect EVs, elucidating their classification, biogenesis, composition, and cargo molecules. Furthermore, we explore techniques for EV engineering and strategies for their precise renal delivery, focusing on cargo loading and transportation, providing a comprehensive perspective. Moreover, this review also discusses and summarizes the diverse therapeutic applications of engineered EVs in CKD, emphasizing their anti-inflammatory, immunomodulatory, renoprotective, and tissue-regenerating effects. It critically evaluates the challenges and limitations in translating EV therapies from laboratory settings to clinical applications, while outlining future prospects and emerging trends.

Lanthanum hydroxide protects kidney through gut microbiota in a rat model of chronic kidney disease.

The progression of chronic kidney diseases (CKD) is complex, influenced by a myriad of factors including gut microbiota. While emerging evidence suggests that gut microbiota can have beneficial effects in managing CKD, it is also recognized that dysbiosis may contribute to the progression of CKD and associated uremic complications. Our previous research has demonstrated the efficacy of lanthanum hydroxide in delaying kidney failure and preserving renal function. However, the role of lanthanum hydroxide in modulating gut microbiota in this context remains unclear. In our study, we induced CKD in rats using adenine, leading to gut microbial dysbiosis, kidney pathology, and disturbances in amino acid metabolism. In this adenine-induced CKD model with hyperphosphatemia, treatment with lanthanum hydroxide improved renal function. This improvement was associated with the restoration of gut microbial balance and an increase in urine ammonium metabolism. These results suggest that the therapeutic potential of lanthanum hydroxide in CKD may be partly due to its ability to reshape gut microbiota composition. This study underscores the significance of lanthanum hydroxide in kidney protection, attributing its benefits to the modulation of gut microbiota in a rat model of CKD.

Does home blood pressure monitoring improve blood pressure-related outcomes in people living with chronic kidney disease? A systematic review.

High blood pressure is an important risk factor for cardiovascular disease and disease progression in chronic kidney disease (CKD). Evidence on the effects of home blood pressure monitoring (HBPM) is limited. This review aimed to determine the effect of HBPM on systolic (SBP) and diastolic blood pressure (DBP) in patients with CKD. We searched medical literature databases for eligible studies presenting pre- and post-data for interventions utilizing HBPM. Study quality was assessed using the NHLBI tools for quality assessment. Heterogeneity prohibited a meta-analysis so estimates of effects were calculated along a sign test to examine the probability of observing the given pattern of positive effect direction. Eighteen studies were included (n = 1187 participants, mean age 56.7 [± 7.7] years). In 15 studies, HBPM was conducted within the context of additional high-level tailored support. Overall, the quality of n = 7/18 studies was rated as "good"; n = 6/18 were "fair," and n = 5/18 were rated as "poor." Interventions utilizing HBPM had a significant effect on SBP, with 14/16 studies favoring the intervention (88% [95% CI: 62%-98%], P = .002). Favorable effects were also seen on DBP (73% [95% CI: 45%-92%], P = .059). HBPM had a favorable effect on blood pressure goal attainment (86% [95% CI: 42%-100%], P = .062). HBPM in patients with CKD as part of a multicomponent intervention may lead to clinically significant reductions in blood pressure; however, research is needed to support the validity of this claim due to the high heterogeneity across the studies included.

Causality between allergic diseases and kidney diseases: a two-sample Mendelian randomization study.

Background: Evidence from observational studies and clinical trials suggests that the allergic diseases (ADs) are associated with kidney diseases (KDs). However, the causal association between them remains to be determined. We used bidirectional two-sample Mendelian randomization (MR) analysis to evaluate the potential causality between them. Methods: Mendelian randomization (MR) was performed using publicly available genome-wide association study (GWAS) summary datasets. Inverse variance weighted (IVW), weighted median, MR-Egger regression, simple mode, and weighted mode methods are used to evaluate the causality between ADs and KDs. Sensitivity and heterogeneity analyses were used to ensure the stability of the results. Results: The MR results indicated that genetic susceptibility to ADs was associated with a higher risk of CKD [odds ratio (OR) = 1.124, 95% CI = 1.020-1.239, p = 0.019] and unspecified kidney failure (OR = 1.170, 95% CI = 1.004-1.363, p = 0.045) but not with kidney stone, ureter stone or bladder stone (OR = 1.001, 95% CI = 1.000-1.002, p = 0.216), other renal or kidney problem (OR = 1.000, 95% CI = 1.000-1.001, p = 0.339), urinary tract or kidney infection (OR = 1.000, 95% CI = 0.999-1.001, p = 0.604), kidney volume (OR = 0.996, 95% CI = 0.960-1.033, p = 0.812) and cyst of kidney (OR = 0.914, 95% CI = 0.756-1.105, p = 0.354). No causal evidence of KDs on ADs was found in present study. Conclusion: Results from MR analysis indicate a causal association between ADs and CKD and unspecified kidney failure. These findings partly suggest that early monitoring of CKD risk in patients with ADs is intentional.

Overview of the Evolution of Hypertension: From Ancient Chinese Emperors to Today.

Hypertension is one of the most commonly treated conditions in modern medical practice, but despite its long history, it was largely ignored until the midpoint of the 20th century. This article will review the origins of elevated blood pressure from when it was first appreciated in 2600 BC to its most recent emerging treatments. Awareness of sustained elevations in blood pressure goes back to the Chinese Yellow Emperor's Classic of Internal Medicine (2600 BC); even then, salt was appreciated as a contributor to elevated pressure. Early treatments included acupuncture, venesection, and bleeding by leeches. About 1000 years later, the association between the palpated pulse and the development of heart and brain diseases was described by Ebers Papyrus (1550 BC). But really, it has only been since well after World War II that hypertension has finally been appreciated as the cause of so much heart, stroke, and kidney disease. We review the development of effective treatments for hypertension while acknowledging that so many people with hypertension in need of treatment have unacceptably poor blood pressure control. We explore why, despite our considerable and growing knowledge of hypertension, it remains a significant public health problem globally.

ML-CKDP: Machine learning-based chronic kidney disease prediction with smart web application.

Chronic kidney diseases (CKDs) are a significant public health issue with potential for severe complications such as hypertension, anemia, and renal failure. Timely diagnosis is crucial for effective management. Leveraging machine learning within healthcare offers promising advancements in predictive diagnostics. In this paper, we developed a machine learning-based kidney diseases prediction (ML-CKDP) model with dual objectives: to enhance dataset preprocessing for CKD classification and to develop a web-based application for CKD prediction. The proposed model involves a comprehensive data preprocessing protocol, converting categorical variables to numerical values, imputing missing data, and normalizing via Min-Max scaling. Feature selection is executed using a variety of techniques including Correlation, Chi-Square, Variance Threshold, Recursive Feature Elimination, Sequential Forward Selection, Lasso Regression, and Ridge Regression to refine the datasets. The model employs seven classifiers: Random Forest (RF), AdaBoost (AdaB), Gradient Boosting (GB), XgBoost (XgB), Naive Bayes (NB), Support Vector Machine (SVM), and Decision Tree (DT), to predict CKDs. The effectiveness of the models is assessed by measuring their accuracy, analyzing confusion matrix statistics, and calculating the Area Under the Curve (AUC) specifically for the classification of positive cases. Random Forest (RF) and AdaBoost (AdaB) achieve a 100% accuracy rate, evident across various validation methods including data splits of 70:30, 80:20, and K-Fold set to 10 and 15. RF and AdaB consistently reach perfect AUC scores of 100% across multiple datasets, under different splitting ratios. Moreover, Naive Bayes (NB) stands out for its efficiency, recording the lowest training and testing times across all datasets and split ratios. Additionally, we present a real-time web-based application to operationalize the model, enhancing accessibility for healthcare practitioners and stakeholders. Web app link: https://rajib-research-kedney-diseases-prediction.onrender.com/.

Caracterización del paciente diabético como antecedente para una intervención educativa / Characterization of diabetic patients as a background for an educational intervention

Introducción: La diabetes mellitus es una enfermedad no transmisible con una elevada comorbilidad, sobre todo, vinculada a la enfermedad renal crónica. La caracterización del paciente diabético, según variables epidemiológicas y los conocimientos de la enfermedad renal crónica que presentan, deben preceder a la valoración clínica y a la intervención educativa dirigida a modificar estilos de vida como parte de la atención primaria de salud. Objetivos: Caracterizar a pacientes diabéticos del Policlínico Santa Clara, según variables epidemiológicas seleccionadas, y la comorbilidad vinculada con la enfermedad renal crónica. Métodos: Se realizó un estudio descriptivo-exploratorio a los pacientes diabéticos en el consultorio médico de la familia 16-11 del Policlínico Santa Clara, de octubre del 2019 a junio del 2022. La población estuvo conformada por 79 pacientes diabéticos y la muestra por 60, según criterios de inclusión y exclusión. Se utilizaron técnicas de análisis estadístico: análisis de frecuencias simples, estadística descriptiva y la prueba de independencia de Chi cuadrado. Resultados: Predominó el sexo masculino; grupo etario de 55-59; diabetes mellitus tipo 2 y cifras elevadas de tensión arterial correlacionadas con la diabetes. Además, existió un nivel bajo de conocimientos acerca de las enfermedades renales crónicas. Conclusiones: Los resultados obtenidos permiten confirmar la relevancia de este tipo de estudios para elevar el nivel de conocimientos sobre la relación entre el padecimiento de diabetes mellitus y la enfermedad renal crónica, para contribuir a mejorar la calidad de vida de este grupo poblacional a través de una intervención educativa previamente orientada.

Introduction: diabetes mellitus is a non-communicable disease with high comorbidity and especially linked to chronic kidney disease. Characterization of diabetic patients according to epidemiological variables and knowledge of their chronic kidney disease must precede the clinical assessment and educational intervention aimed at modifying lifestyles as part of primary health care. Objectives: to characterize diabetic patients from Santa Clara Polyclinic according to selected epidemiological variables as well as the comorbidity linked to chronic kidney disease. Methods: a descriptive exploratory study was carried out on diabetic patients belonged to the 16-11 doctor's office in Santa Clara Polyclinic from October 2019 to June 2022. The population was made up of 79 diabetic patients and 60 formed the sample according to inclusion and exclusion criteria. Statistical analysis techniques such as descriptive statistics, simple frequency analysis and the Chi- square independence test were used. Results: males, age group 55-59 years, type 2 diabetes mellitus and high blood pressure levels correlated with diabetes predominated. Besides, a low level of knowledge on chronic kidney diseases was identified. Conclusions: the obtained results confirm the relevance of this type of studies to raise the level of knowledge on the relationship between diabetes mellitus and chronic kidney disease in order to contribute to the improvement of the quality of life of this population group through a previously oriented educational intervention.

A CKD Clinical Decision Support System: A Cluster Randomized Clinical Trial in Primary Care Clinics.

Rationale & Objective: The study aimed to develop, implement, and evaluate a clinical decision support (CDS) system for chronic kidney disease (CKD) in a primary care setting, with the goal of improving CKD care in adults. Study Design: This was a cluster randomized trial. Setting & Participants: A total of 32 Midwestern primary care clinics were randomly assigned to either receive usual care or CKD-CDS intervention. Between April 2019 and March 2020, we enrolled 6,420 patients aged 18-75 years with laboratory-defined glomerular filtration rate categories of CKD Stage G3 and G4, and 1 or more of 6 CKD care gaps: absence of a CKD diagnosis, suboptimal blood pressure or glycated hemoglobin levels, indication for angiotensin-converting enzyme inhibitor or angiotensin receptor blocker but not prescribed, a nonsteroidal anti-inflammatory agent on the active medication list, or indication for a nephrology referral. Intervention: The CKD-CDS provided personalized suggestions for CKD care improvement opportunities directed to both patients and clinicians at primary care encounters. Outcomes: We assessed the proportion of patients meeting each of 6 CKD-CDS quality metrics representing care gap resolution after 18 months. Results: The adjusted proportions of patients meeting quality metrics in CKD-CDS versus usual care were as follows: CKD diagnosis documented (26.6% vs 21.8%; risk ratio [RR], 1.17; 95% CI, 0.91-1.51); angiotensin-converting enzyme inhibitor or angiotensin receptor blocker prescribed (15.9% vs 16.1%; RR, 0.95; 95% CI, 0.76-1.18); blood pressure control (20.4% vs 20.2%; RR, 0.98; 95% CI, 0.84-1.15); glycated hemoglobin level control (21.4% vs 22.1%; RR, 1.00; 95% CI, 0.80-1.24); nonsteroidal anti-inflammatory agent not on the active medication list (51.5% vs 50.4%; RR, 1.03; 95% CI, 0.90-1.17); and referral or visit to a nephrologist (38.7% vs 36.1%; RR, 1.02; 95% CI, 0.79-1.32). Limitations: We encountered an overall reduction in expected primary care encounters and obstacles to point-of-care CKD-CDS utilization because of the coronavirus disease 2019 pandemic. Conclusions: The CKD-CDS intervention did not lead to a significant improvement in CKD quality metrics. The challenges to CDS use during the coronavirus disease 2019 pandemic likely influenced these results. Funding: National Institute of Diabetes and Digestive and Kidney Diseases (R18DK118463). Trial Registration: clinicaltrials.gov Identifier: NCT03890588.

This study aimed to improve the management of chronic kidney disease (CKD) through a clinical decision support (CDS) system. It involved 32 primary care clinics and 6,420 patients with CKD who had 1 or more of 6 CKD care improvement opportunities. The CDS provided personalized suggestions to both patients and clinicians about CKD care opportunities during primary care visits. After 18 months, the study found no significant differences between patients in clinics with CKD-CDS compared with usual care in diagnosing CKD, prescribing recommended medications, controlling blood pressure or glycated hemoglobin, nonsteroidal anti-inflammatory agent usage, or nephrology referrals. The coronavirus disease 2019 pandemic may have influenced results by introducing unforeseen implementation challenges, reduced visits, and less than expected CDS exposure.

Hypertension Related Co-Morbidities and Complications in Women of Sub-Saharan Africa: A Brief Review.

Hypertension is the leading cause of cardiovascular disease in women, and sub-Saharan African (SSA) countries have some of the highest rates of hypertension in the world. Expanding knowledge of causes, management, and awareness of hypertension and its co-morbidities worldwide is an effective strategy to mitigate its harms, decrease morbidities and mortality, and improve individual quality of life. Hypertensive disorders of pregnancy (HDPs) are a particularly important subset of hypertension, as pregnancy is a major stress test of the cardiovascular system and can be the first instance in which cardiovascular disease is clinically apparent. In SSA, women experience a higher incidence of HDP compared with other African regions. However, the region has yet to adopt treatment and preventative strategies for HDP. This delay stems from insufficient awareness, lack of clinical screening for hypertension, and lack of prevention programs. In this brief literature review, we will address the long-term consequences of hypertension and HDP in women. We evaluate the effects of uncontrolled hypertension in SSA by including research on heart disease, stroke, kidney disease, peripheral arterial disease, and HDP. Limitations exist in the number of studies from SSA; therefore, we will use data from countries across the globe, comparing and contrasting approaches in similar and dissimilar populations. Our review highlights an urgent need to prioritize public health, clinical, and bench research to discover cost-effective preventative and treatment strategies that will improve the lives of women living with hypertension in SSA.