Early Chronic Kidney Disease Research Articles

Neutrophil extracellular traps in the cross-talk between periodontitis and chronic kidney disease

BackgroundThe objective was to evaluate the level of neutrophil extracellular traps (NETs) in patients with chronic kidney disease (CKD) and periodontitis, and to explore the relationship between NETs and both diseases.Methods63 CKD and 40 non-CKD participants were recruited and underwent periodontal examination, among which 35 early CKD patients underwent periodontal therapy. The concentrations of NETs were determined by dsDNA assay in gingival crevicular fluid (GCF) and plasma, and by flow cytometry or immunofluorescence assay in blood and gingival tissues. The correlations between NETs and clinical parameters were analyzed. The influence of periodontal therapy on periodontitis, CKD and NETs concentrations was also evaluated.ResultsCKD patients had higher concentrations of NETs in plasma than non-CKD patients, and NETs concentrations were also increased in both GCF and plasma of patients with periodontitis than that of periodontally healthy patients. NETs concentrations were positively correlated with increased clinical parameters of CKD and periodontitis. The positive correlation between CKD and periodontitis was demonstrated. Moreover, periodontal therapy ameliorated periodontitis and CKD, and reduced NETs concentrations in GCF of patients.ConclusionsThis study revealed that NETs might be a possible bridge between periodontitis and CKD, and suggested the potential target for therapy.

Evaluation of urinary volatile organic compounds as a novel metabolomic biomarker to assess chronic kidney disease progression

BackgroundThere is a need to develop accurate and reliable non-invasive methods to evaluate chronic kidney disease (CKD) status and assess disease progression. Given it is recognized that dysregulation in metabolic pathways occur from early CKD, there is a basis in utilizing metabolomic biomarkers to monitor CKD progression. Volatile Organic Compounds (VOCs), a form of metabolomic biomarker, are gaseous products of metabolic processes in organisms which are typically released with greater abundance in disease conditions when there is dysregulation in metabolism. How urinary VOCs reflect the abnormal metabolic profile of patients with CKD status is unknown. Our study aimed to explore this.MethodsIndividuals aged 18–75 years undergoing kidney biopsy were included. Pre-biopsy urine samples were collected. All biopsy samples had an interstitial fibrosis and tubular atrophy (IFTA) grade scored by standardized assessment. Urine supernatant was extracted from residue and sampled for stir bar sorptive extraction followed by Gas chromatography–mass spectrometry (GC-MS) analysis. Post-processing of GC-MS data separated complex mixtures of VOCs based on their volatility and polarity. Mass-to-charge ratios and fragment patterns were measured for individual VOCs identification and quantification. Linear discriminant analysis (LDA) was performed to assess the ability of urinary VOCs in discriminating between IFTA 0 (‘no or minimal IFTA’ i.e. <10%, IFTA), IFTA 1 (‘mild IFTA’ i.e. 10–25% IFTA) and IFTA ≥ 2 (‘moderate or severe IFTA’ i.e. >25% IFTA). Linear regression analysis adjusting for age, sex, estimated glomerular filtration rate, diabetes mellitus (DM) status, and albuminuria was conducted to determine significantly regulated urinary VOCs amongst the groups.Results64 study participants (22 individuals IFTA 0, 15 individuals IFTA 1, 27 individuals IFTA ≥ 2) were included. There were 34 VOCs identified from GC-MS which were statistically associated with correct classification between the IFTA groups, and LDA demonstrated individuals with IFTA 0, IFTA 1 and IFTA ≥ 2 could be significantly separated by their urinary VOCs profile (p < 0.001). Multivariate linear regression analysis reported 4 VOCs significantly upregulated in the IFTA 1 compared to the IFTA 0 group, and 2 VOCs significantly upregulated in the IFTA ≥ 2 compared to the IFTA 1 group (p < 0.05). Significantly upregulated urinary VOCs belonged to one of four functional groups - aldehydes, ketones, hydrocarbons, or alcohols.ConclusionsWe report novel links between urinary VOCs and tubulointerstitial histopathology. Our findings suggest the application of urinary VOCs as a metabolomic biomarker may have a useful clinical role to non-invasively assess CKD status during disease progression.

Five-year outcomes of a holistic programme for managing early chronic kidney disease in primary care.

Holistic Approach in Lowering and Tracking Chronic Kidney Disease (HALT-CKD) is a nationwide programme that was introduced in 2017 to combat CKD in Singapore. This study aims to evaluate outcomes of the HALT-CKD programme and identify factors influencing disease progression among early CKD patients. We conducted a retrospective cohort study involving adult patients aged 21 to 80 with CKD stages G1-G3A, recruited from 5 Singapore polyclinics between 2017 and 2018. The primary outcome-time to progression to advanced CKD (G3B-G5)-was tracked until March 2023, based on patients' last known serum creatinine levels. Descriptive statistics and Cox regression were used. Patients who followed up with other institutions, were deceased or defaulted without developing (or experiencing) the outcome were censored. We studied 3800 patients (mean age: 61.9 years) for a median of 4.7 years. Among them, 12.6% developed advanced CKD despite statistically significant improvements in HbA1c, blood pressure and albuminuria levels. Increasing age, female sex, clinic, baseline creatinine, diastolic blood pressure and HbA1c significantly shortened time to CKD progression. Macro-albuminuria at baseline (hazard ratio [HR] 1.77, 95% confidence interval [CI] 1.19- 2.61) and at analysis (HR 2.22, 95% CI 1.55-3.19) significantly accelerated advanced CKD progression. Patients who had their angiotensin-converting enzyme inhibitor (ACEi)/angiotensin receptor blocker (ARB) dose reduced or discontinued progressed to advanced CKD earlier (HR 1.92, 95% CI 1.50-2.45). Counselling and sodium-glucose cotransporter-2 inhibitor (SGLT2i) use did not significantly delay CKD progression. Maintaining optimal ACEi/ARB dosage is essential to delay CKD progression. Premature cessation or reduction of this dosage should be discouraged. Further research on counselling and SGLT2i use in early CKD is needed to address the growing burden of CKD.

Preterm Birth and Kidney Health: From the Womb to the Rest of Life.

Chronic kidney disease (CKD) is a widespread condition often resulting from multiple factors, including maternal influences. These risk factors not only heighten the likelihood of developing CKD but increase the risk of a preterm birth. Adverse events during nephrogenesis can disrupt kidney development, leading to a reduced number of nephrons. As survival rates for preterm infants improve, more individuals are living into adulthood, thereby elevating their risk of CKD later in life. This review aims to explore the connections between preterm birth, kidney development, and the increased risk of CKD, while proposing practical solutions for the future through a multidisciplinary approach. We examine human studies linking preterm birth to negative kidney outcomes, summarize animal models demonstrating kidney programming and reduced nephron numbers, and consolidate knowledge on common mechanisms driving kidney programming. Additionally, we discuss factors in the postnatal care environment that may act as secondary insults contributing to CKD risk, such as acute kidney injury (AKI), the use of nephrotoxic drugs, preterm nutrition, and catch-up growth. Finally, we outline recommendations for action, emphasizing the importance of avoiding modifiable risk factors and implementing early CKD screening for children born preterm. Together, we can ensure that advancements in kidney health keep pace with improvements in preterm care.

Dietary phosphorus and renal disease in cats: where are we?

Phosphorus is an essential nutrient required for the normal function of every cell in the body and a deficiency in dietary phosphorus may lead to adverse effects. Conversely, high dietary phosphorus may cause kidney damage in otherwise healthy adult cats, particularly when provided in highly bioavailable forms and when the calcium-to-phosphorus ratio is low. For cats that have chronic kidney disease (CKD), phosphorus is the most important mineral in its pathogenesis and morbidity. As the disease progresses, elevated phosphorus may increase the risk of complications such as soft tissue mineralization, which can lead to a further decrease in renal function. Additionally, the hormones secreted in response to increased circulating phosphorus have harmful effects, such as bone resorption, and can cause cardiovascular pathology. Very low phosphorus diets can also be problematic in cats with early CKD, potentially leading to hypercalcemia. There is currently a lack of maximum safety limits for dietary phosphorus in accepted nutritional guidelines in North American and Europe, which makes it difficult to assess the safety of some higher phosphorus cat foods. Additionally, information regarding phosphorus bioavailability is unknown for many diets and there are no commercially available tests. Similarly, there is no consensus regarding phosphorus requirement and recommended intake in cats with International Renal Interest Society stage 1-4 CKD despite there being targets for serum phosphorus. This review evaluates dietary phosphorus in healthy cats and cats with renal disease, and describes how newer research is informing evolving clinical approaches in feline nutrition. The article is aimed at general practitioners, internal medicine specialists and veterinary nutritionists. Information provided in this article is drawn from the published literature.

Evaluation of Novel Biomarker of Early Atherosclerosis in Patients With Chronic Kidney Disease in Wasit Governorate

The aim of the study was to evaluate some Biomarkers in patients with athreoscelerosis in Wasit Province. Atherosclerosis is a chronic arterial disease and a major cause of vascular death. Fatty streaks in arterial walls gradually develop into atheroma and characteristic plaques. The acute rupture of these atheromatous plaques causes local thrombosis, leading to partial or total occlusion of the affected artery. The clinical consequences of these plaques depend on their site and the degree and speed of vessel occlusion . Its major clinical manifestations include ischemic heart disease (IHD), ischemic stroke, and peripheral arterial disease. The study took place in the a hemodialysis unit Al-Zahraa Teaching Hospital in Wasit Governorate during the period from November 2023 to April 2024. This study aimed to examine risk factors (age, gender, high blood pressure, smoking, left ventricular hypertrophy, diabetes mellitus, dyslipidemia, physical inactivity) for atherosclerosis in the general population and patients with chronic kidney disease. Also studying the effect of some novel biomarkers (Homocysteine, Fibrinogen, myeloperoxidase, lipoprotein-associated phospholipase A2, pentraxin 3). The study include (90) samples: (60) patients suffering from early atherosclerosis and chronic kidney disease (dialysis stage) and 30 samples of healthy people (control group), their ages ranged from (40 to 70 years). The samples were divided into two age groups, where the first group had an average age of 40-55 years and the second group was 56-70 years old , the categories were divided equally into males and females Samples were collected based on the incidence of kidney disease first, and then the main risk factors of early atherosclerosis were relied upon, which are (smoking, age, sex, dyslipidemia, hypertension, diabetes, left ventricle valve, physical inactivity). The results of our study regarding diagnostic markers of atherosclerosis showed a significant increase in biomarkers (MPO, PTX3, HCy, FG and LpPLA2)of infected people at p ≥ 0.5. In patients with atherosclerosis the level of new biomarkers showed a significant increase in serum of infected people compared to healthy people at p&lt;0.5. This is an important indication of the importance of these biomarkers in detecting the disease.

Prevalence and associated factors of chronic kidney disease among Truká Indigenous adults in Cabrobó, Brazil: a population-based study

The prevalence of chronic kidney disease (CKD) is increasing worldwide, especially in developing countries, due to factors such as lifestyle changes and the rise of non-communicable diseases. Populations living in socioeconomically disadvantaged areas are subject to a higher burden of CKD. However, the burden of CKD on Brazilian Indigenous people, especially those undergoing an advanced urbanisation process, has not yet been described. This cross-sectional study included 1715 Truká Indigenous adults from Cabrobó, Brazil. CKD was defined according to the Kidney Disease Improving Global Outcomes guidelines classification as a urinary albumin/creatinine ratio ≥30mg/g and/or an estimated glomerular filtration rate <60mL/min/1.73m2. Univariate and multiple logistic regression models were used to evaluate factors associated with CKD. Odds ratio (OR) with a 95% confidence interval (CI) was used to measure association. Out of the 1654 participants analysed (61 excluded due to missing data), the prevalence of CKD was 10% (95% CI, 8.6%-11.5%), with a higher prevalence in women compared to men (12.4% versus 6.9%, p<0.001). The mean age was 40.5 years, with 55.6% being women. In univariate analysis, female sex (OR, 1.9; 95% CI, 1.3-2.7), age ≥60 years (OR, 4.6; 95% CI, 3.2-6.6), cardiovascular disease (OR, 2.1; 95% CI, 1.1-4.1), and dyslipidemia (OR, 1.6; 95% CI, 1.1-2.4) were identified as associated factors with CKD. Multiple logistic regression analysis identified age ≥60 years, female sex, and dyslipidemia as independently associated factors with CKD. The prevalence of CKD among Truká Indigenous adults analysed is high and affects a higher proportion of women. Our study found no association between hypertension, diabetes, obesity, and CKD risk, despite their high prevalence. These findings assist in developing early CKD detection strategies in Brazilian Indigenous communities, supporting disease treatment and prevention. National Council for Scientific and Technological Development (CNPq)-Ministry of Science, Technology, and Innovation of Brazil, and the Maria Emília Foundation.

Advancements in Machine Learning and Deep Learning for Early Diagnosis of Chronic Kidney Diseases: A Comprehensive Review

Chronic kidney disease (CKD) is a prevalent and debilitating condition worldwide, characterized by progressive loss of kidney function over time. Early detection plays a crucial role in mitigating its impact on patient health and healthcare systems. In recent years, there has been a burgeoning interest in leveraging machine learning (ML) and deep learning (DL) techniques to enhance the early diagnosis of CKD. This comprehensive review explores the advancements in ML and DL models applied to CKD diagnosis, focusing on their ability to integrate diverse data sources including clinical biomarkers, imaging modalities, and patient demographics. Key ML algorithms such as Support Vector Machines (SVM), Random Forests (RF), and neural network architectures like Convolutional Neural Networks (CNNs) and Long Short-Term Memory networks (LSTMs) are examined in the context of their performance in predicting CKD progression, classifying disease stages, and identifying at-risk populations. Furthermore, the review discusses challenges such as data quality, model interpretability, and integration into clinical practice, alongside emerging trends in explainable AI, transfer learning, federated learning, and integration with electronic health records (EHRs). By synthesizing findings from recent literature, this paper aims to provide insights into current methodologies, identify gaps for future research, and underscore the transformative potential of ML and DL in revolutionizing early CKD diagnosis and management..

Updated guidelines for chronic kidney disease.

Chronic kidney disease (CKD) is an increasingly common condition worldwide that leads to substantial mortality. Research in the past decade has informed significant advances in preventing CKD or delaying its progression, mainly through new medications. This progress, however, requires adequate screening and identification of early CKD to truly transform patient outcomes. Revised guidelines from the Kidney Disease: Improving Global Outcomes consortium of experts aim to help clinicians incorporate these advances into practice. This article summarizes key updates from the guidelines regarding the evaluation and management of CKD that can lead to better patient outcomes.

Classification and segmentation of kidney MRI images for chronic kidney disease detection

Chronic Kidney Disease (CKD) is a common ailment with significant public health implications, underscoring the critical importance of early detection and diagnosis for effective management. Our research focuses on utilizing deep learning models to accurately classify and segment kidney MRI images, aiding in the timely detection and diagnosis of CKD. Utilizing the Zenodo dataset comprising 1299 kidney MRI images from 100 T2-weighted abdomen MRI scans, our investigation reveals that Vision Transformers (ViT) based model EfficientNet_b1 exhibited superior performance compared to other models. It achieved an accuracy of 94.38% in distinguishing between healthy and CKD cases in kidney MRI image classification. Moreover, the pretrained models Densenet201 and VGG19, as well as the ViT-based models EfficientNet_b1 and tf_mobilenetv3_large_075, demonstrate remarkable sensitivity and accuracy while compared to identifying kidney MRI images which highlights the effectiveness of deep learning architectures in identifying diseases. Additionally, our segmentation analysis reveals that our proposed network, Resnet18-Self-ONN-UNet++, adeptly delineates kidney structures. The network shows remarkable performance in medical diagnosis and treatment planning, with an Intersection over Union (IoU) of 82.34% and DS of 91.57% when integrated with the Contrast Limited Adaptive Histogram Equalization (CLAHE) preprocessing technique and Simultaneous truth and performance level estimation (STAPLE) as post processing technique. In summary, deep learning-driven kidney MRI image classification and segmentation enhance medical imaging analysis, potentially aiding in early CKD diagnosis and treatment, thereby addressing critical public health concerns, and enhancing patient outcomes.

The Lived Experience of Patients with Chronic Kidney Disease: Insights From DISCOVER CKD

Introduction: Chronic kidney disease (CKD) can have a profound impact on patients’ lives. However, multinational data on patients’ lived experience with CKD are scarce. Methods: Individuals from the prospective cohort of DISCOVER CKD (NCT04034992), an observational cohort study, were recruited to participate in one-to-one telephone interviews to explore their lived experience with CKD. A target of 100 participant interviews was planned across four countries (Japan, Spain, the UK, and the USA). These qualitative interviews, lasting ∼60–90 min, were conducted in the local language by trained interviewers with specific experience in CKD, between January and June 2023. Transcribed interviews were translated into English for coding and analysis. Data were coded using qualitative research software. Results: Of the 105 participants interviewed, 103 were included in the final analysis. The average time since CKD diagnosis was 9.5 years, and at least half (50.5%) of participants had CKD stage 3A or 3B. CKD diagnosis was an emotional experience, driven by worry (n = 29/103; 28.2%) and shock (n = 26/103; 25.2%), and participants often reported feeling inadequately informed. Additional information was frequently sought, either online or via other healthcare providers. The proportion of participants reporting no impacts of CKD on their lives was highest in those with CKD stage 1 and 2 (64.3%). Conversely, every participant in the CKD stage 5 on dialysis group reported some impact of CKD on their lives. Across all participants, the most reported impacts were anxiety or depression (37.9%) or ability to sleep (37.9%). The frequency of the reported impacts appeared to increase with disease severity, with the highest rates observed in the dialysis group. In that group, the most frequently reported impact was on the ability to work (80.0%). Conclusion: Findings from this multinational qualitative study suggest that patients may experience symptoms and signs of disease prior to diagnosis; however, these are often nonspecific and may not be directly associated with CKD. Once diagnosed, the burden of CKD can have a diverse, negative impact on various aspects of patients’ lives. This highlights the need for early identification of at-risk individuals, and the importance of early CKD diagnosis and management with guideline-directed therapies to either prevent further deterioration of CKD or slow its progression, thus reducing symptom burden and improving quality of life.

Compliance with a Healthful Plant-Based Diet Is Associated with Kidney Function in Patients with Autosomal Dominant Polycystic Kidney Disease.

Autosomal dominant polycystic kidney disease (ADPKD) is a genetic kidney disorder with multiple cyst formation that progresses to chronic kidney disease (CKD) and end-stage kidney disease. Plant-based diets have attracted considerable attention because they may prevent CKD development. This study investigated whether adherence to a plant-based diet is associated with kidney function in patients with ADPKD. The overall plant-based diet index (PDI), healthful PDI (hPDI), and unhealthful PDI (uPDI) were calculated using dietary intake data. Among 106 ADPKD patients, 37 (34.91%) were classified as having advanced CKD (eGFR < 60 mL/min/1.73 m2). The overall PDI and hPDI were lower, but the uPDI was higher in patients with advanced CKD than in those with early CKD. The hPDI was negatively correlated with the neutrophil-to-lymphocyte ratio and platelet-to-lymphocyte ratio. Moreover, the hPDI was inversely associated with advanced CKD [odds ratio (OR): 0.117 (95% confidence interval (CI): 0.039-0.351), p < 0.001], and the uPDI was positively associated with advanced CKD [OR: 8.450 (95% CI: 2.810-25.409), p < 0.001]. The findings of the current study demonstrate that greater adherence to a healthful plant-based diet is associated with improved kidney function in ADPKD patients.

Barriers to early diagnosis of chronic kidney disease and use of sodium-glucose cotransporter-2 inhibitors for renal protection: A comprehensive review and call to action.

Chronic kidney disease (CKD) affects approximately 13% of people globally, including 20%-48% with type 2 diabetes (T2D), resulting in significant morbidity, mortality, and healthcare costs. There is an urgent need to increase early screening and intervention for CKD. We are experts in diabetology and nephrology in Central Europe and Israel. Herein, we review evidence supporting the use of sodium-glucose cotransporter-2 (SGLT2) inhibitors for kidney protection and discuss barriers to early CKD diagnosis and treatment, including in our respective countries. SGLT2 inhibitors exert cardiorenal protective effects, demonstrated in the renal outcomes trials (EMPA-KIDNEY, DAPA-CKD, CREDENCE) of empagliflozin, dapagliflozin, and canagliflozin in patients with CKD. EMPA-KIDNEY demonstrated cardiorenal efficacy across the broadest renal range, regardless of T2D status. Renoprotective evidence also comes from large real-world studies. International guidelines recommend first-line SGLT2 inhibitors for patients with T2D and estimated glomerular filtration rate (eGFR) ≥20 mL/min/1.73 m2, and that glucagon-like peptide-1 receptor agonists may also be administered if required for additional glucose control. Although these guidelines recommend at least annual eGFR and urine albumin-to-creatinine ratio screening for patients with T2D, observational studies suggest that only half are screened. Diagnosis is hampered by asymptomatic early CKD and under-recognition among patients with T2D and clinicians, including limited knowledge/use of guidelines and resources. Based on our experience and on the literature, we recommend robust screening programmes, potentially with albuminuria self-testing, and SGLT2 inhibitor reimbursement at general practitioner (GP) and specialist levels. High-tech tools (artificial intelligence, smartphone apps, etc.) are providing exciting opportunities to identify high-risk individuals, self-screen, detect abnormalities in images, and assist with prescribing and treatment adherence. Better education is also needed, alongside provision of concise guidelines, enabling GPs to identify who would benefit from early initiation of renoprotective therapy; although, regardless of current renal function, cardiorenal protection is provided by SGLT2 inhibitor therapy.

Deep learning radiomics based on ultrasound images for the assisted diagnosis of chronic kidney disease.

This study aimed to explore the value of ultrasound (US) images in chronic kidney disease (CKD) screening by constructing a CKD screening model based on grey-scale US images. According to the CKD diagnostic criteria, 1049 patients from Tongde Hospital of Zhejiang Province were retrospectively enrolled in the study. A total of 4365 renal US images were collected from these patients. Convolutional neural networks were used for feature extractions and a screening model was constructed by fusing ResNet34 and texture features to identify CKD and its stage. A comparative analysis was performed to compare the diagnosis results of the model with physicians. When diagnosing CKD or non-CKD, the receiver operating characteristic curve (AUC) of our model was 0.918 and that of the senior physician group was 0.869 (p < .05). For the diagnosis of CKD stage, the AUC of our model for CKD G1-G3 was 0.781, 0.880, and 0.905, respectively, while the AUC of the senior physician group for CKD G1-G3 was 0.506, 0.586, and 0.796, respectively; all differences were statistically significant (p < .05). The diagnostic efficiency of our model for CKD G4 and G5 reached the level of the senior physicians group. Specifically, the AUC of our model for CKD G4-G5 was 0.867 and 0.931, respectively, while the AUC of the senior physician group for CKD G4-G5 was 0.838 and 0.963, respectively (all p > .05). Our deep learning radiomics model is more effective than senior physicians in the diagnosis of early CKD.

Clinical and Economic Impact of Early Diagnosis of Chronic Kidney Disease in General Practice: The Endorse Study.

The underdiagnosis of chronic kidney disease (CKD) remains a significant public health concern. The Early chroNic kiDney disease pOint of caRe Screening (ENDORSE) project aimed to evaluate the clinical and economic implications of a targeted training intervention for general practitioners (GPs) to enhance CKD awareness and early diagnosis. Data on estimated Glomerular Filtration Rate (eGFR) and Urinary Albumin-Creatinine Ratio (uACR) were collected by 53 Italian GPs from 112,178 patients at baseline and after six months. The intervention involved six months of hybrid training provided by 11 nephrologists, which included formal lectures, instant messaging support, and joint visits for complex cases. The results demonstrated a substantial increase in the use of eGFR (+44.7%) and uACR (+95.2%) tests. This led to a 128.9% rise in the number of individuals screened for CKD using the KDIGO classification, resulting in a 62% increase in CKD diagnoses. The intervention's impact was particularly notable in high-risk groups, including patients with type 2 diabetes, hypertension, and heart failure. A budget impact analysis projected cumulative five-year savings of €1.7 million for the study cohort. When these findings were extrapolated to the entire Italian CKD population, potential savings were estimated at €106.6 million, highlighting significant cost savings for the national health service. The clinical simulation assumed that early diagnosed CKD patients would be treated according to current indications for dapagliflozin, which slows disease progression. The ENDORSE model demonstrated that targeted training for GPs can significantly improve early CKD detection, leading to better patient outcomes and considerable economic benefits. This approach shows promise for broader implementation to address the underdiagnosis of CKD on a national and potentially international scale.

Nanotherapeutic kidney cell-specific targeting to ameliorate acute kidney injury

Acute kidney injury (AKI) increases the risk of in-hospital death, adds to expense of care, and risk of early chronic kidney disease. AKI often follows an acute event such that timely treatment could ameliorate AKI and potentially reduce the risk of additional disease. Despite therapeutic success of dexamethasone in animal models, clinical trials have not demonstrated broad success. To improve the safety and efficacy of dexamethasone for AKI, we developed and characterized a novel, kidney-specific nanoparticle enabling specific within-kidney targeting to proximal tubular epithelial cells provided by the megalin ligand cilastatin. Cilastatin and dexamethasone were complexed to H-Dot nanoparticles, which were constructed from generally recognized as safe components. Cilastatin/Dexamethasone/H-Dot nanotherapeutics were found to be stable at plasma pH and demonstrated salutary release kinetics at urine pH. In vivo, they were specifically biodistributed to the kidney and bladder, with 75% recovery in the urine and with reduced systemic toxicity compared to native dexamethasone. Cilastatin complexation conferred proximal tubular epithelial cell specificity within the kidney in vivo, and enabled dexamethasone delivery to the proximal tubular epithelial cell nucleus in vitro. The Cilastatin/Dexamethasone/H-Dot nanotherapeutic improved kidney function and reduced kidney cellular injury when administered to male C57BL/6 mice in two translational models of AKI (rhabdomyolysis and bilateral ischemia reperfusion). Thus, our design-based targeting and therapeutic loading of a kidney-specific nanoparticle resulted in preservation of the efficacy of dexamethasone, combined with reduced off-target disposition and toxic effects. Hence, our study illustrates a potential strategy to target AKI and other diseases of the kidney.

Serum and Urinary Uromodulin in Dogs with Early Chronic Kidney Disease vs. Healthy Canine Population.

Serum and urinary uromodulin are evaluated as potential biomarkers of kidney disease. The aim of our research was to select a more appropriate form of uromodulin for the diagnosis of early stages of chronic kidney disease (CKD). We also focused on the influence of age and gender in one breed on uromodulin and on the possible interbreed differences. Serum uromodulin had the lowest values in dogs younger than 2 years but no effect of gender, breed, or CKD was observed. Urinary uromodulin indexed to urinary creatinine was significantly reduced in dogs in stage 2 of CKD (p = 0.003) in contrast to uromodulin converted to urine specific gravity. Urinary uromodulin with both corrections was significantly lower in Belgian shepherds compared to German shepherds (p < 0.0001, p = 0.0054) but was not influenced by gender or age. In stage 1 of CKD, urinary uromodulin correlated with kidney disease markers SDMA (p = 0.0424, p = 0.0214) and UPC (p = 0.0050, p = 0.0024). Urinary uromodulin appears to be more associated with CKD than serum uromodulin. Further studies with a larger number of patients are needed for the suitability of urinary uromodulin as a marker of early-stage disease.

The Effect of Sleep Habits on Quality of Life in Pediatric Patients With Chronic Kidney Disease.

Sleep disturbance has been studied in adult patients with early and end-stage chronic kidney disease (CKD). However, there are limited publications on the pediatric patient population. This paper evaluated the association between sleep disturbances and quality of life (QoL) inpediatricpatients with CKD. The study included 22 patients and 22 healthy controls from the pediatric nephrology outpatient clinic.All participants completed the Turkish Generic Health-Related Quality of Life Questionnaire for Children and Adolescents (HRQoLQ) and the Child Sleep Habits Questionnaire(CSHQ). Patients diagnosed with CKD were compared in terms of HRQoLQ and CSHQ scores within themselves as kidney replacement therapy (KRT) recipients and non-recipients and with the control group. The mean HRQoLQ total score of the patients was 89.0 ± 12.4 and the mean CSHQ total score was 46.7 ± 5.6; there was no correlation between the total scores (p=0.599). CSHQ total and subgroup scores were similar in patients with and without KRT. The CSHQ total and subgroup median scores were not different in the patient and control groups. According to the HRQoL scale, the total QoL score and the physical and emotional well-being subscale scores were lower in patients receiving KRT than in those not receiving KRT. Sleep problems and HRQoL should not be underestimated in the pediatric CKD population, especially in patients receiving KRT. Large-scale studies with long-term outcomes are needed to understand better and improve QoL.

Supplementation of vitamin E as an addition to a commercial renal diet does not prolong survival of cats with chronic kidney disease

BackgroundThe aim of this double-blind, placebo-controlled study was to investigate the effect of vitamin E supplementation as an addition to a commercial renal diet on survival time of cats with different stages of chronic kidney disease (CKD). In addition, we were interested whether vitamin E supplementation affects selected oxidative stress and clinical parameters. Thirty-four cats with CKD and 38 healthy cats were included in the study. Cats with CKD were classified according to the IRIS Guidelines; seven in IRIS stage 1, 15 in IRIS stage 2, five in IRIS stage 3 and seven in IRIS stage 4. Cats with CKD were treated according to IRIS Guidelines. Cats with CKD were randomly assigned to receive vitamin E (100 IU/cat/day) or placebo (mineral oil) for 24 weeks in addition to standard therapy. Plasma malondialdehyde (MDA) and protein carbonyl (PC) concentrations, DNA damage of peripheral lymphocytes and plasma vitamin E concentrations were measured at baseline and four, eight, 16 and 24 weeks thereafter. Routine laboratory analyses and assessment of clinical signs were performed at each visit.ResultsVitamin E supplementation had no effect on the survival time and did not reduce the severity of clinical signs. Before vitamin E supplementation, no significant differences in vitamin E, MDA and PC concentrations were found between healthy and CKD cats. However, plasma MDA concentration was statistically significantly higher (p = 0.043) in cats with early CKD (IRIS stages 1 and 2) than in cats with advanced CKD (IRIS stages 3 and 4). Additionally, DNA damage was statistically significantly higher in healthy cats (p ≤ 0.001) than in CKD cats. Plasma vitamin E concentrations increased statistically significantly in the vitamin E group compared to the placebo group four (p = 0.013) and eight (p = 0.017) weeks after the start of vitamin E supplementation. During the study and after 24 weeks of vitamin E supplementation, plasma MDA and PC concentrations and DNA damage remained similar to pre-supplementation levels in both the placebo and vitamin E groups.ConclusionsVitamin E supplementation as an addition to standard therapy does not prolong survival in feline CKD.

Guidelines for clinical evaluation of chronic kidney disease in early stages

BackgroundFor the development of pharmaceutical products in kidney field, appropriate surrogate endpoints which can predict long-term prognosis are needed as an alternative to hard endpoints, such as end-stage kidney disease. Though international workshop has proposed estimated glomerular filtration rate (GFR) slope reduction of 0.5–1.0 mL/min/1.73 m /year and 30% decrease in albuminuria/proteinuria as surrogate endpoints in early and advanced chronic kidney disease (CKD), it was not clear whether these are applicable to Japanese patients.MethodsWe analyzed J-CKD-DB and CKD-JAC, Japanese databases/cohorts of CKD patients, and J-DREAMS, a Japanese database of patients with diabetes mellitus to investigate the applicability of eGFR slope and albuminuria/proteinuria to the Japanese population. Systematic review on those endpoints was also conducted including the results of clinical trials published after the above proposal.ResultsOur analysis showed an association between eGFR slope and the risk of end-stage kidney disease. A 30% decrease in albuminuria/proteinuria over 2 years corresponded to a 20% decrease in the risk of end-stage kidney disease patients with baseline UACR ≥ 30 mg/gCre or UPCR ≥ 0.15 g/gCre in the analysis of CKD-JAC, though this analysis was not performed on the other database/cohort. Those results suggested similar trends to those of the systematic review.ConclusionThe results suggested that eGFR slope and decreased albuminuria/proteinuria may be used as a surrogate endpoint in clinical trials for early CKD (including diabetic kidney disease) in Japanese population, though its validity and cutoff values must be carefully considered based on the latest evidence and other factors.