Early Stages Of Chronic Kidney Disease Research Articles

Early-Stage Chronic Kidney Disease and Related Health Care Spending

The global burden of chronic kidney disease (CKD) is substantial and potentially leads to higher health care resource use. To examine the association between early-stage CKD and health care spending and its changes over time in the general population. Cohort study using nationwide health checkup and medical claims data in Japan. Participants included individuals aged 30 to 70 years with estimated glomerular filtration rates (eGFR) of 30 mL/min/1.73 m2 or greater at the baseline screening in 2014. Data analyses were conducted from April 2021 to October 2023. The CKD stages at baseline, defined by the eGFR and proteinuria, were as follows: eGFR of 60 mL/min/1.73 m2 or greater without proteinuria, eGFR of 60 mL/min/1.73 m2 or greater with proteinuria, eGFR of 30 to 59 mL/min/1.73 m2 without proteinuria, and eGFR of 30 to 59 mL/min/1.73 m2 with proteinuria. The primary outcome was excess health care spending, defined as the absolute difference in health care spending according to the baseline CKD stages (reference group: eGFR ≥60 mL/min/1.73 m2 without proteinuria) in the baseline year (2014) and in the following 5 years (2015 to 2019). Of the 79 988 participants who underwent a health checkup (mean [SD] age, 47.0 [9.4] years; 22 027 [27.5%] female), 2899 (3.6%) had an eGFR of 60 mL/min/1.73 m2 or greater with proteinuria, 1116 (1.4%) had an eGFR of 30 to 59 mL/min/1.73 m2 without proteinuria, and 253 (0.3%) had an eGFR of 30 to 59 mL/min/1.73 m2 with proteinuria. At baseline, the presence of proteinuria and an eGFR less than 60 mL/min/1.73 m2 were associated with greater excess health care spending (adjusted difference, $178; 99% CI, $6-$350 for proteinuria; $608; 99% CI, $233-$983 for an eGFR of 30-59 mL/min/1.73 m2; and $1254; 99% CI, $134-$2373 for their combination). The study consistently found excess health care spending over the following 5 examined years. In this cohort study of nationwide health checkup and medical claims data in Japan, early-stage CKD was associated with excess health care spending over the 5 examined years, and the association was more pronounced with a more advanced disease stage.

Development and deployment of a nationwide predictive model for chronic kidney disease progression in diabetic patients.

Chronic kidney disease (CKD) is a major complication of diabetes and a significant disease burden on the healthcare system. The aim of this work was to apply a predictive model to identify high-risk patients in the early stages of CKD as a means to provide early intervention to avert or delay kidney function deterioration. Using the data from the National Diabetes Database in Singapore, we applied a machine-learning algorithm to develop a predictive model for CKD progression in diabetic patients and to deploy the model nationwide. Our model was rigorously validated. It outperformed existing models and clinician predictions. The area under the receiver operating characteristic curve (AUC) of our model is 0.88, with the 95% confidence interval being 0.87 to 0.89. In recognition of its higher and consistent accuracy and clinical usefulness, our CKD model became the first clinical model deployed nationwide in Singapore and has been incorporated into a national program to engage patients in long-term care plans in battling chronic diseases. The risk score generated by the model stratifies patients into three risk levels, which are embedded into the Diabetes Patient Dashboard for clinicians and care managers who can then allocate healthcare resources accordingly. This project provided a successful example of how an artificial intelligence (AI)-based model can be adopted to support clinical decision-making nationwide.

Prevalence of infertility and pregnancy loss among individuals with kidney disease in the Hispanic Community Health Study/Study of Latinos.

Hispanic/Latino individuals are less likely to receive optimal treatment for chronic kidney disease than non-Hispanic whites. This may be particularly detrimental for women of reproductive age as chronic kidney disease increases risk for infertility, menstrual irregularities, and pregnancy loss. While these maternal outcomes have been associated with advanced chronic kidney disease, their occurrence in early chronic kidney disease is unclear. Using baseline (2008-2011) and second study visit (2014-2017) data from the Hispanic Community Health Study/Study of Latinos, we retrospectively assessed the prevalence of chronic kidney disease as well as the association between chronic kidney disease and self-reported infertility, cessation of menses, hysterectomy, and nonviable pregnancy loss (experienced at less than 24 weeks gestation) in women of reproductive age (18-45 years). Multivariable survey logistic regression analyses determined the unadjusted and multivariable-adjusted prevalence odds ratios with 95% confidence intervals between chronic kidney disease and the separate outcomes. Among 2589 Hispanic/Latino women included (mean age = 31.4 years), 4.6% were considered to have chronic kidney disease. In adjusted analyses, women with chronic kidney disease did not have a significantly increased odds of infertility (odds ratio = 1.02, 95% confidence interval = 0.42-2.49), cessation of menses (odds ratio = 1.25, 95% confidence interval = 0.52-3.04), or hysterectomy (odds ratio = 1.17, 95% confidence interval = 0.61-2.25) compared to those without chronic kidney disease. In those with chronic kidney disease, the adjusted odds of a nonviable pregnancy loss occurring after baseline visit were increased (odds ratio = 2.11, 95% confidence interval = 0.63-7.02) but not statistically significance. The presence of early stage chronic kidney disease did not confer a significant risk of infertility, cessation of menses, or nonviable pregnancy loss.

РАННЯЯ ДИАГНОСТИКА ХРОНИЧЕСКОЙ БОЛЕЗНИ ПОЧЕК У ДЕТЕЙ С ПОМОЩЬЮ АЛГОРИТМОВ МАШИННОГО ОБУЧЕНИЯ

Background. Diagnosis of early-stage chronic kidney disease (CKD) is a global challenge, as late-stage disease is more commonly diagnosed. The development of modeling methods for making management decisions aimed at improving the efficiency of early diagnosis of CKD is an important scientific and practical task, which can be greatly supported by the use of machine learning algorithms (MLA). Aim. To improve the accuracy of diagnosis of CKD using data from history, clinical-instrumental, genetic examination and machine learning algorithms (MLA). Methods. Data were obtained from a single-center retrospective catamnestic cohort study (2011–2022) of children with CKD stage 1–4 aged 1 to 17 years. The main group included 128 children with CKD, and the comparison group included 30 children without any kidney disease. Two groups were comparable by sex and age. The data of anamnesis, clinical-instrumental and genetic examination were used to build a model for CKD diagnosis. The model was built using the MLA multivariate logistic regression (MLR). Three variables were used in the model: erythrocyte sedimentation rate in blood (β = 0,392; p<0,001); erythrocytes in urine (β = 1,225; p<0,001); and asthenic physique (β = 5,792; p<0,001). Results. A diagnostics model was obtained allowing prediction of CKD on a test sample with accuracy of 90,3% [80,6; 96,8], sensitivity of 92,0% [81,5; 100,0], specificity of 83,3% [50,0; 100,0], ROC-AUC = 90,0% [77,2; 100,0]. The resulting model is of excellent quality (>90%) as the ROC-AUC is 0,90 on the test sample. The cut-off point value of the probability of CKD is 0,25. Conclusions. We developed and tested the model that diagnoses early-stage CKD in children with high accuracy

Algorithm for Diagnosing Cardiovascular Pathology in Diabetes Mellitus

Introduction. The association of diabetes mellitus (DM) and cardiovascular diseases (CVD) is due to common pathophysiological processes that determine the prognosis and progression of both diseases. We studied the factors associated with the risk of developing cardiovascular pathology to create an algorithm for diagnosing it in patients diabetes mellitus. Patients and methods. A total of 449 patients (126 men and 323 women) with type 1 diabetes (133) and type 2 diabetes (316) were examined. The median age was 63 (53; 70) years. Serum cystatin C, C-reactive protein (CRP), homocysteine, interleukin-6 (IL-6), N-terminal natriuretic peptide (NTproBNP) and brain natriuretic peptide (BNP) levels, fibroblast growth factor (FGF-23) levels, tumor necrosis factor (TNF-α), chemokine MIG, endothelial growth factor (VEGF-A), chemokine RANTES were determined in all patients. Instrumental research methods included echocardiographic examination and ultrasound of the lower extremity and brachiocephalic arteries. Logistic regression and ROC analysis were used to assess the prognostic value of markers. Results. Cystatin C levels ≥0.96 mg/l were associated with increased natriuretic peptides in patients with diabetes and early stages of CKD (with GFR>60), IL-6 levels ≥2.13 mg/ml and FGF-23 ≥0.9 pmol/ l — with the risk of increasing natriuretic peptides, and IL-6 ≥0.9 pmol/l — with the risk of increase in left ventricular mass index. Based on the obtained results, we developed an algorithm for diagnosis of cardiovascular pathology in patients with diabetes mellitus. Conclusions. In the present study, we identified markers associated with the risk of adverse cardiovascular events in patients with diabetes and their diagnostic value.

Effect of Tyrosine Kinase Inhibitor Therapy on Estimated Glomerular Filtration Rate in Patients with Chronic Myeloid Leukemia

IntroductionThe advent of tyrosine kinase inhibitors (TKIs) was revolutionary in the management of chronic myeloid leukemia (CML). Although TKIs were generally considered to be safe, they can be associated with renal injury. We evaluated the effect of TKIs on renal functions in a cohort of patients with long-term follow-up. Material and MethodsWe retrospectively examined patients with chronic phase CML treated with TKIs. We analyzed the estimated glomerular filtration rate (eGFR) of patients from the initiation of TKI to the last follow-up. eGFR values of CML patients were compared to those of patients with stage 1 or 2 chronic kidney disease (CKD). ResultsA total of 195 patients with CML and 138 patients with CKD were examined. eGFR decline was 1.556 ml/min/1.73m2/year for patients with CML (P = .221). Patients receiving second-generation TKIs (2GTKI) were estimated to have 0.583 ml/min/1.73m2 higher eGFR value than that of the imatinib group, but it was not significant (P = .871). eGFR of patients who had used bosutinib had a downward trend. Duration of TKI therapy, age, and hypertension were found to be significant factors in eGFR decline for CML patients. Lower baseline GFR was associated with an increased risk of CKD development. ConclusionImatinib could result in a decline in eGFR which was clinically similar to early-stage CKD patients. We did not observe significant kidney function deterioration in patients receiving 2GTKIs including dasatinib and nilotinib. We recommend close renal function monitoring in patients receiving imatinib, especially for elderly patients with lower baseline eGFR and hypertension.

Wireless Detection of Trace Ammonia: A Chronic Kidney Disease Biomarker.

Elevated levels of ammonia in breath can be linked to medical complications, such as chronic kidney disease (CKD), that disturb the urea balance in the body. However, early stage CKD is usually asymptomatic, and mass screening is hindered by high instrumentation and operation requirements and accessible and reliable detection methods for CKD biomarkers, such as trace ammonia in breath. Enabling methods would have significance in population screening for early stage CKD patients. We herein report a method to effectively immobilize transition metal selectors in close proximity to a single-walled carbon nanotube (SWCNT) surface using pentiptycene polymers containing metal-chelating backbone structures. The robust and modular nature of the pentiptycene metallopolymer/SWCNT complexes creates a platform that accelerates sensor discovery and optimization. Using these methods, we have identified sensitive, selective, and robust copper-based chemiresistive ammonia sensors that display low parts per billion detection limits. We have added these hybrid materials to the resonant radio frequency circuits of commercial near-field communication (NFC) tags to achieve robust wireless detection of ammonia at physiologically relevant levels. The integrated devices offer a noninvasive and cost-effective approach for early detection and monitoring of CKD.

Effectiveness of the Nurse-led Self and Family Management Support Program among Adults with Early-stage Chronic Kidney Disease: A Randomized Controlled Trial

Chronic kidney disease is a significant health problem that leads to severe complications and premature death. Adults with early-stage chronic kidney disease need to maintain renal function and prevent the progression, which can be achieved through effective self-management. This randomized control trial with a two-arm pre-post-test aimed to investigate the effectiveness of the Nurse-led Self and Family Management Support Program for increasing disease knowledge and self-management among adults with early-stage chronic kidney disease. The sample consisted of dyads of 64 adults with the disease and their family members. The dyads were randomly assigned to the experimental arm (n = 32) and the control arm (n = 32). The experimental arm received the Nurse-led Self and Family Management Support Program, while the control arm received only usual care. Data was collected using a demographic data recording form, the Disease Knowledge Scale, and the Chronic Kidney Disease Self-Management Scale. Data analysis was undertaken using descriptive statistics, two-way repeated ANOVA with post hoc test, and independent t-test. From the results, the participants in the experiment arm had better disease knowledge and self-management than the control group at 4, 8, and 12 weeks after the program and were better than before the program. Nurses can apply this program to encourage individuals and family members to be involved in providing all aspects of support for self-management for adults with early-stage chronic kidney disease. However, further testing in other settings is needed.

Review of the applicability of the DASH diet for patients with chronic kidney disease and chronic liver disease

Hypertension is a significant risk factor for cardiovascular diseases, and the DASH diet effectively lowers blood pressure. However, individuals with Chronic Kidney Disease (CKD) and Chronic Liver Disease (CLD) need adaptations in potassium and sodium/water intake to adhere to the DASH diet. This literature review examines the applicability of the DASH diet for patients with CKD and CLD by analyzing findings from a comprehensive search of relevant academic databases. The review explores various sources, including clinical studies, research articles, and expert recommendations, to assess the effectiveness and suitability of the DASH diet in managing the dietary needs of individuals with CKD and CLD. The review reveals that the DASH diet, with its emphasis on reduced sodium intake and increased consumption of fruits, vegetables, whole grains, and lean proteins, shows promising results in managing blood pressure and improving overall cardiovascular health in individuals with early stage CKD and CLD. Furthermore, the review concludes that individuals with advanced CKD and CLD should exercise caution when considering the DASH diet, as modifications are necessary to accommodate their specific conditions. For patients with advanced CKD, careful management of potassium intake is essential to prevent hyperkalemia; while individuals with late-stage CLD should monitor both sodium and water intake to avoid dilutional hyponatremia. Additionally, the review also emphasized the importance of individualized dietary modifications and consultations with healthcare professionals for optimizing the benefits of the DASH diet, especially for those patients with later stages of CKD and CLD.

Clinical value of serum MMP-3 in chronic kidney disease

BackgroundChronic kidney disease (CKD) is defined as the progressive deterioration of renal parenchyma and decline in renal unit function. In the early stages of CKD(G1 + G2), symptoms are usually not obvious and cannot be effectively recognized on the basis of available clinical markers. Progression to the middle and late stages of CKD results in severe kidney damage with multiple complications causing adverse outcomes, including death. Therefore, the early diagnosis and monitoring of CKD is critical. Matrix metalloproteinase-3 (MMP-3), an extracellular matrix–degrading enzyme, plays an important role in kidney diseases. However, the clinical significance of serum MMP-3 levels in CKD has rarely been reported. MethodsWe quantified the serum MMP-3 levels of 237 patients with CKD and 96 healthy individuals by using a highly sensitive time-resolved fluorescence immunoassay and analyzed differences in MMP-3 levels among the stages of CKD and the correlations of these changes with clinical indicators. ResultsThe serum MMP-3 concentrations of patients with CKD (171.76 ± 165.22 ng/mL) were significantly higher than those of healthy controls (34.05 ± 22.93 ng/mL; P < 0.0001). In CKD, serum MMP-3 levels were significantly correlated with estimated glomerular filtration rate (eGFR) (r = − 0.5804, P < 0.0001), serum creatinine (CREA) (r = 0.5823, P < 0.0001), blood urea nitrogen (BUN) (r = 0.6106, P < 0.0001), and protein-to-creatinine ratio (r = 0.4992, P < 0.0001). Randomized forest analysis finds CREA, BUN, and MMP-3 most significant influences on CKD disease severity. The critical value of MMP-3 concentration of 40.39 ng/mL combined with eGFR was effective in diagnosing positive patients in the early (G1 + G2) stage of CKD and showed a positivity rate of 73.45 %. Moreover, in the early stages of CKD, patients with CKD who had serum MMP-3 concentration > 100 ng/mL had more severe renal impairment and inflammation than those with CKD who have lower serum MMP-3 concentrations. ConclusionElevated serum MMP-3 levels are correlated with decreased kidney function in CKD progression, and patients with concomitant inflammation may express high levels of serum MMP-3. Serum MMP-3 may assist eGFR in improving the diagnosis of patients with early CKD.

Effect of dietary protein intake on cognitive function in the elderly with chronic kidney disease: analysis of the National Health and Nutrition Examination Survey 2011–2014

Background Cognitive dysfunction is prevalent among the elderly diagnosed with chronic kidney disease (CKD). Low protein diets are used for retarding the progression of CKD in clinical practice. Nonetheless, the impact of dietary protein consumption on cognitive function in this population remains uncertain. Methods We recruited 2306 participants (≥60 years) from 2011 to 2014 National Health and Nutrition Examination Survey (NHANES). 24-h dietary recall questionnaire was utilized to evaluate protein intake. Cognitive function was measured using the Consortium to Establish a Registry for Alzheimer’s Disease (CERAD), Animal Fluency Test (AFT), and Digit Symbol Substitution Test (DSST). Participants’ characteristics were analyzed, and the interaction between protein consumption and CKD on cognitive impairment were analyzed using a logistic regression model. Results We divided participants into three groups based on CKD stages: no CKD, CKD stage G1 to G2 (19%), and CKD stage G3 to G5 (18%). The average protein intake was 0.97 g/(kg·d). In the higher protein intake group, CKD stages G1 to G2 elevated the risk of immediate memory impairment (OR: 2.441, 95% Cl: 1.161–5.132 for protein consumption in 1.0-1.2g/(kg·d); OR: 2.225, 95% Cl: 1.015–4.876 for protein consumption in >1.2 g/(kg·d)). However, no similar resuts were observed in the lower protein intake group. In addition, the interaction between CKD status and protein intake on immediate memory was statistically significant (p = .041). Conclusion A higher probability of cognitive impairment in the elderly with early-stage CKD may be linked to higher protein intake. Low protein diets may be a potential strategy to release cognitive impairment in the elderly with early-stage CKD.

Real-life use of tolvaptan in ADPKD: a retrospective analysis of a large Canadian cohort

Tolvaptan is the first disease-modifying drug proven to slow eGFR decline in high-risk patients with ADPKD. However, barriers from the patient perspective to its use in real-life settings have not been systemically examined in a large cohort. This was a single-center, retrospective study of 523 existing or new patients with ADPKD followed at the Center for Innovative Management of PKD in Toronto, Ontario, between January 1, 2016 to December 31, 2018. All patients underwent clinical assessment including total kidney volume measurements and Mayo Clinic Imaging Class (MCIC). Those who were deemed to be at high risk were offered tolvaptan with their preference (yes or no) and reasons for their choices recorded. Overall, 315/523 (60%) patients had MCIC 1C-1E; however, only 96 (30%) of them were treated with tolvaptan at their last follow-up. Among these high-risk patients, those not treated versus treated with tolvaptan were more likely to have a higher eGFR (82 ± 26 vs. 61 ± 27 ml/min/1.73 m2), CKD stages 1–2 (79% vs. 41%), and MCIC 1C (63% vs. 31%). The most common reasons provided for not taking tolvaptan were lifestyle preference related to the aquaretic effect (51%), older age ≥ 60 (12%), and pregnancy/family planning (6%). In this real-world experience, at least 60% of patients with ADPKD considered to be at high risk for progression to ESKD by imaging were not treated with tolvaptan; most of them had early stages of CKD with well-preserved eGFR and as such, were prime targets for tolvaptan therapy to slow disease progression. Given that the most common reason for tolvaptan refusal was the concern for intolerability of the aquaretic side-effect, strategies to mitigate this may help to reduce this barrier to tolvaptan therapy.

Prevalence of and factors associated with uncontrolled hypertension among patients with early chronic kidney disease attending tertiary hospitals in Dodoma, Tanzania: a cross-sectional study

ObjectiveTo determine the prevalence of uncontrolled hypertension and its associated factors among patients with early chronic kidney disease (CKD) attending medical outpatient clinics at tertiary hospitals in Dodoma, Tanzania.DesignCross-sectional study.SettingTwo...

Comparative effectiveness of first-line antihypertensive drug classes on the maintenance of estimated glomerular filtration rate (eGFR) in real world primary care

Renin-angiotensin system inhibitors (RASi), particularly angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin II receptor blockers (ARBs), are commonly used in the treatment of hypertension and are recommended for kidney protection. Uncertainty remains about the effectiveness of RASi being used as first-line antihypertensive therapy on eGFR maintenance compared to its alternatives, especially for those with no or early-stage chronic kidney disease (CKD). We conducted a retrospective cohort study of 19,499 individuals (mean age 64.1, 43.5% males) from primary care in Singapore with 4.5 median follow-up years. The study cohort included newly diagnosed individuals with hypertension (whose eGFR was mainly in CKD stages G1-G2) and initiated on ACEIs, ARBs, beta-blockers (BBs), calcium channel blockers (CCBs) or diuretics (Ds) as first-line antihypertensive monotherapy. We compared the estimated glomerular filtration rate (eGFR) curve before/after the drug initiation over time of patients under different drug classes and analyzed the time to declining to a more advanced stage CKD. Inverse probability of treatment weighting (IPTW) was used to adjust for baseline confounding factors. Two key findings were observed. First, after initiating antihypertensive drugs, the eGFR almost maintained the same as the baseline in the first follow-up year, compared with dropping 3 mL/min/1.73 m2 per year before drug initiation. Second, ARBs were observed to be slightly inferior to ACEIs (HR = 1.14, 95% CI = (1.04, 1.23)) and other antihypertensive agents (HR = 1.10, 95% CI = (1.01, 1.20)) in delaying eGFR decline to a more advanced CKD stage in the study population. Our results showed that initiating antihypertensive agents can significantly maintain eGFR for those newly diagnosed patients with hypertension. However, RASi may not be superior to other antihypertensive agents in maintaining eGFR levels for non-CKD or early stages CKD patients.

A Pilot Study for the Kidney Effects of Voxelotor in Sickle Cell Anemia

The kidneys are among the most commonly affected organ systems in sickle cell anemia (SCA) and an estimated 15% of deaths in patients with SCA are attributed to kidney failure (PMID 7993409). Angiotensin converting enzyme-inhibitors and angiotensin receptor blockers have been adopted to treat SCA-related chronic kidney disease (CKD) from the non-SCA literature, although demonstrated efficacy in SCA CKD has been marginal in a limited number of small, short-term studies (PMID 28589652). Therapies that directly target the pathophysiology of SCA-related kidney disease may stabilize or improve kidney function. Both the rate of hemolysis and the degree of anemia are associated with the development and progression of CKD in SCA (PMID 24329963, 21523807). Voxelotor inhibits hemoglobin polymerization in SCA red blood cells in the deoxygenated state, leading to a reduction in the rate of hemolysis and an increase in hemoglobin concentration. We conducted a pilot study to determine whether voxelotor can improve kidney function in adults with SCA (NCT 04335721). SCA (HbSS or HbSβ 0-thalassemia) patients ≥ 18 years old and with urine dipstick-defined hemoglobinuria (+ for blood &amp; ≤ 2 red blood cells/high power field), CKD stage 1 or 2 (urine albumin-to-creatinine ratio [ACR] ≥ 30 mg/g &amp; estimated glomerular filtration rate [eGFR] ≥ 60 mL/min/1.73m 2), and hemoglobin concentrations of 5.5 - 10.5 g/dL were eligible. The eGFR was calculated using the CKD-EPI 2009 creatinine-based equation without the race coefficient and the 2012 cystatin C-based equation. Patients were randomized to voxelotor 1,500mg/day for 48 weeks or standard of care, as defined by their primary SCA provider. First or second void urines were collected for urine ACR measurements. The primary endpoint was the change in urine ACR from the mean values at baseline and screening versus the mean values at 47 and 48 week visits. One patient randomized to standard of care was started on voxelotor at week 24 by his provider to improve his hemoglobin concentration. This patient is included in the voxelotor treatment group in combined analysis; the change in laboratory measures in this patient is based upon changes from the mean of values at week 12 and 24 to week 47 and 48 visits. Median and range values are provided. Between 3/2021 and 6/2022, 8 SCA patients with hemoglobinuria and urine ACR &amp;gt; 30mg/g crt observed during routine clinic visits were screened and 6 met the inclusion criteria. The median age of the enrolled cohort was 36 (27 - 63) years, 4 were male, 4 were on stable doses of hydroxyurea (median dose 1000mg/day; 500 - 1500mg/day) and 2 were on stable doses of lisinopril (5, 20mg/day) for at least 90 days before screening. Two other patients had been on lisinopril in the past but developed hyperkalemia prior to enrollment. The median values of kidney function measures at screening and baseline study visits were as follows: urine ACR, 251 (32 - 3132) and 392 (80 - 3101) mg/g crt; creatinine-based eGFR, 109 (93 - 136) and 115 (88 - 137) mL/min/1.73m 2; and cystatin C-based eGFR, 82 (61 - 141) and 85 (61 - 128) mL/min/1.73m 2, respectively. SCA patients who received voxelotor (n = 4) had a median increase in hemoglobin concentration of +0.9 g/dL (-0.4 - +2.6 g/dL) and reductions in indirect bilirubin concentration of -2.2 mg/dL (0 - -4 mg/dL) and reticulocyte % of -2.7% (-1.2 - -4.9%). Urine ACR (-59%, -21% - -100%) improved in SCA patients treated with voxelotor but worsened in those who received standard of care without voxelotor (n = 2) (+86.3%, 64 - 108%) (P=0.009) (Figure 1A). 24-hour urine protein concentrations also improved in those that received voxelotor (-45%, -25% - -100%) but increased in those who did not receive voxelotor (+122%, 113 - 131%) (P = 0.002) (Figure 1B). Changes in creatinine- and cystatin-C based eGFR from baseline were not significantly different between patients who received voxelotor and those who did not. This pilot study demonstrates that SCA patients with hemoglobinuria and early stages of CKD treated with voxelotor may have significant improvements in urine ACR and proteinuria after 24 - 48 weeks of therapy. These preliminary results support the concept that improving hemolytic anemia could be a targeted therapeutic approach to reduce biomarkers of kidney dysfunction, and they warrant larger, prospective clinical studies.

LncRNA FAS-AS1 served as a diagnostic biomarker of end-stage renal disease and mediated vascular calcification via regulating oxidative stress and inflammation

PurposeVascular calcification is a frequently occurring complication of end-stage renal disease (ESRD). This study focused on the significance of long non-coding RNA Fas cell surface death receptor-antisense 1(lncRNA FAS-AS1) in ESRD-related vascular calcification aiming to explore a potential biomarker for the detection. MethodsThe study enrolled 65 healthy individuals, 79 ESRD patients (48 patients with vascular calcification), and 93 early-stage (I-IV) chronic kidney disease (CKD) patients. The expression of FAS-AS1 in serum was evaluated by real-time quantitative polymerase chain reaction (PCR). The diagnostic potential of FAS-AS1 was assessed in discriminating ESRD patients, vascular calcification, and the severity of vascular calcification. In vitro, the vascular smooth muscle cells (VSMCs) were treated with a hyperphosphatemia medium to evaluate the effect of FAS-AS1 on VSMCs calcification. ResultsElevated serum FAS-AS1 was observed in ESRD patients, which could discriminate from healthy individuals and early-stage CKD patients. FAS-AS1 was associated with the development of ESRD and the occurrence of vascular calcification. FAS-AS1 was also upregulated in vascular calcification patients, especially the patients with severe calcification, which showed diagnostic significance in evaluating vascular calcification degrees. Calcified VSMCs showed significantly increased levels of Ca2+, reactive oxygen species (ROS), tumor necrosis factor-α (TNF-α), and interleukin 6 (IL-6), which was attenuated by silencing FAS-AS1. ConclusionsFAS-AS1 discriminated ERSD patients and was associated with the occurrence of vascular calcification. The knockdown of FAS-AS1 suppressed hyperphosphatemia-induced vascular calcification via alleviating oxidative stress and inflammation.

Osteoporosis in Renal Disease.

Osteoporosis is a disorder characterized by decreased bone mass and skeletal fragility with increased fracture risk. Chronic kidney disease presents with wide range of bone metabolic disorders, including osteoporosis. Osteoporosis prevalence is high in early stages of CKD; whereas in late stages, it coexists with renal osteodystrophy. Risk factors for osteoporosis include advancing age, low bone mineral density (BMD), glucocorticoid therapy, smoking, alcohol intake, etc. The diagnosis of osteoporosis in renal disease is made after assessment of BMD, in addition to exclusion of chronic kidney disease-mineral bone disorder (CKD-MBD), eliciting history of prior fragility fractures and relevant laboratory investigations. The treatment of osteoporosis varies with the different stages of CKD, with management in stages 1-3 being similar to the general population. Special emphasis must be laid on prevention of fractures as well.

An Intelligent Diagnostic System to Analyze Early-Stage Chronic Kidney Disease for Clinical Application

Chronic kidney disease (CKD) is a progressive condition characterized by the gradual deterioration of kidney functions, potentially leading to kidney failure if not promptly diagnosed and treated. Machine learning (ML) algorithms have shown significant promise in disease diagnosis, but in healthcare, clinical data pose challenges: missing values, noisy inputs, and redundant features, affecting early-stage CKD prediction. Thus, this study presents a novel, fully automated machine learning approach to tackle these complexities by incorporating feature selection (FS) and feature space reduction (FSR) techniques, leading to a substantial enhancement of the model’s performance. A data balancing technique is also employed during preprocessing to address data imbalance issue that is commonly encountered in clinical contexts. Finally, for reliable CKD classification, an ensemble characteristics-based classifier is encouraged. The effectiveness of our approach is rigorously validated and assessed on multiple datasets, and the clinical relevancy of the strategy is evaluated on the real-world therapeutic data collected from Bangladeshi patients. The study establishes the dominance of adaptive boosting, logistic regression, and passive aggressive ML classifiers with 96.48% accuracy in forecasting unseen therapeutic CKD data, particularly in early-stage cases. Furthermore, the effectiveness of the FSR technique in reducing the prediction time significantly is revealed. The outstanding performance of the proposed model demonstrates its effectiveness in addressing the complexity of healthcare CKD data by incorporating the FS and FSR techniques. This highlights its potential as a promising computer-aided diagnosis tool for doctors, enabling early interventions and improving patient outcomes.

Impact of early stages of CKD with and without proteinuria on cardiac remodelling in UK Biobank cohort

Abstract Background Chronic kidney disease (CKD) is an established predictor of left atrial (LA) and left ventricular (LV) morphological and functional changes, which translate into excessive cardiovascular morbidity and mortality. However, a focussed study exploring the impact of early stages of CKD defined as stage 1 (eGFR &amp;gt; 90 mL/min per 1.73 m2 + albuminuria) and stage 2 (eGFR 60–89 mL/min per 1.73 m2) with and without proteinuria on cardiac magnetic resonance (CMR) parameters is lacking. Purpose In this study, we analysed CMR structural and functional changes in participants with early stages of CKD in the UK Biobank population. Methods 41,095 participants from the UK Biobank imaging study were categorised into CKD stages. We calculated eGFR using the CKD-EPI 2021 equation and proteinuria was ascertained by the urinary protein creatinine ratio (defined as &amp;gt;30mg/mmol). We sought associations between CKD stages (exposure) and CMR parameters: LV end-diastolic volume (LVEDV), LV end-systolic volume (LVESV), LV stroke volume (LVSV), LV ejection fraction (LVEF), LV global functional index (LVGFI), LV myocardial contractile function (LVMCF), LV mass (LVM), LV mass-to-volume ratio (LVMVR), LV global longitudinal strain (GLS), LV global radial strain (GRS), LV global circumferential strain (GCS), LA maximum volume and left atrial emptying fraction. In the multivariable regression model, we adjusted for covariates including age, sex, ethnicity, height, body mass index, hypertension, diabetes, smoking status, and hyperlipidaemia Results Among the participants, 26,779 (65.1%) had normal kidney function, 2,787 (6.8%) stage 1 CKD, 10,534 (25.6%) stage 2 CKD without proteinuria, 689 (1.7%) stage 2 CKD with proteinuria, 241 (0.6%) CKD stage 3A (eGFR 59-45mL/min per 1.73 m2) without proteinuria, 28 (0.1%) stage 3A with proteinuria and 37 (0.1%) with more advanced CKD defined as stages 3B and above. Approximately 8 years after characterisation of CKD stages these participants underwent CMR. Using adjusted multivariable regression models setting normal kidney function as the reference group, the presence of proteinuria in stage 3 CKD was associated with smaller LV volume, lower LVM and more impaired LV function (LVSV beta=-11ml, 95% confidence interval (CI): -5 to -16ml and GLS beta=0.9%, 95% CI: 0.2 to 1.7%). Conclusions This study highlights the relationship between proteinuria in the early stages of CKD and cardiac remodelling patterns using CMR. CKD sub-characterisation with presence or absence of proteinuria should be considered for risk stratification.Figure 1

23-valent pneumococcal polysaccharide vaccine and the risk of renal progression in older patients with chronic kidney disease

BackgroundThe 23-valent pneumococcal polysaccharide vaccine (PPSV23) ensures favorable outcomes and reduces the risk of cardiac events in patients on dialysis. However, the effect of PPSV23 vaccination on renal function remains unknown, particularly in patients with chronic kidney disease (CKD). Therefore, we investigated the association between PPSV23 efficacy and renal progression in older patients (age ≥ 75 years) with CKD. MethodsThis multicenter, longitudinal cohort study was conducted using data (2008–2016) from the Epidemiology and Risk Factors Surveillance of CKD database. This database was associated with Taiwan's National Health Insurance Research Database (for period: 2008–2019). A total of 1195 older patients with CKD were recruited from 14 hospitals and communities across Taiwan. Renal progression was defined as a > 25% reduction in estimated glomerular filtration rate from the baseline value. ResultsA significant reduction in the risk of renal progression was observed in patients who had received PPSV23 (adjusted hazard ratio [HR]: 0.57; 95% confidence interval [CI]: 0.35–0.91). However, when stratified by CKD stage, this significant reduction was observed in patients with early-stage CKD but not in those with late-stage CKD. Furthermore, a significant reduction in the risk of renal progression was noted in male patients and those with hypertension. ConclusionOur findings support the protective effect of PPSV23 against renal deterioration in older patients with CKD.