Chronic Kidney Disease Stage Research Articles

The Effect of Denosumab on Risk for Emergently Treated Hypocalcemia by Stage of Chronic Kidney Disease

The Effect of Denosumab on Risk for Emergently Treated Hypocalcemia by Stage of Chronic Kidney Disease

Haemolytic uremic syndrome as a cause of chronic kidney disease stage 5 in children is in retreat: results from the Polish Registry of Kidney Replacement Therapy in children (2000-2023).

Haemolytic uremic syndrome (HUS) is a life-threatening disease with a historically poor prognosis in children receiving maintenance kidney replacement therapy (KRT). This study aimed to analyse the incidence and outcome of chronic kidney disease stage 5 (CKD5) due to Escherichia coli-HUS (STEC-HUS) and complement-mediated HUS (CM-HUS) in children, compared with controls with non-HUS CKD5 over the last 24years. The study included 1488 children undergoing KRT in Poland between 2000 and 2023. Thirty-nine patients with CM-HUS and 18 with STEC-HUS were identified and analysed for incidence, KRT modality and survival. The incidence rate of CKD5 was 0.09 cases/million age-related population (marp) for STEC-HUS and 0.23/marp for CM-HUS, while no new cases have been observed in recent years. CKD5 due to CM-HUS developed significantly earlier from initial HUS manifestation than in STEC-HUS (median 0.2 vs. 9.8years). CM-HUS was associated with younger age at initiation of KRT compared to STEC-HUS and non-HUS controls (median 6.0years vs. 10.9 and 10.9years), with higher risk of death (Hazard Ratio 1.92, 95% confidence interval 0.9-4.13) and worse 5-year kidney graft survival at 77%, 93% and 90%, respectively (p < 0.001). In recent years, both CM-HUS and STEC-HUS have become increasingly rare causes of CKD5 in children. CKD5 due to CM-HUS in the eculizumab era and due to STEC-HUS after improving supportive treatment is exceptional. Children on KRT due to STEC-HUS had a significantly better survival, shorter waiting time for kidney transplantation and better kidney graft survival compared to the CM-HUS group.

The renal-retinal connection - The eye in chronic kidney disease

Chronic kidney disease (CKD) is linked with several systemic complications, including ocular manifestations that can adversely affect quality of life. The prevalence and types of ocular changes in CKD patients, particularly their correlation with disease stages, are not well-documented. This study aims to evaluate the ocular manifestations in CKD and their association with different stages of the disease.A cross-sectional study on 70 CKD patients revealed a high prevalence of ocular abnormalities, including diabetic retinopathy, hypertensive retinopathy, and age-related macular degeneration. These conditions often worsened as CKD progressed, emphasizing the need for regular eye exams in CKD patients to prevent vision loss and address complications promptly. To investigate the prevalence and types of ocular manifestations in patients with chronic kidney disease (CKD) and to analyse their correlation with the stages of CKD. This cross-sectional, descriptive, non-interventional, hospital-based study was conducted over four months from May 2024 to August 2024 in the Department of Nephrology. Seventy patients with diagnosed CKD, aged 18 years and older, were included. Exclusion criteria were patients with reversible causes of renal failure, those who had undergone renal transplantation, and those who did not consent. A comprehensive ocular examination was performed on 140 eyes from the enrolled patients, assessing anterior and posterior segment findings, including visual acuity, eyelid conditions, conjunctival status, lens status, and fundus examination. The study included 38 males (54.3%) and 32 females (45.7%) with a mean age of 57 years. Hypertension and diabetes mellitus were the most common comorbidities, present in 71.4% and 64.3% of patients, respectively. Visual acuity deteriorated with advancing stages of CKD, with significant impairment and blindness observed predominantly in CKD stages 4 and 5. Anterior segment examination revealed that 62% of eyes had immature cataracts, and 38% were pseudophakic. Fundoscopic examination showed that 51.4% of patients had abnormal findings, including non-proliferative and proliferative diabetic retinopathy, hypertensive retinopathy, age-related macular degeneration, and glaucomatous disc changes. The severity of fundus abnormalities increased with the progression of CKD, highlighting a strong correlation between the degree of renal dysfunction and ocular health. Ocular manifestations are common in CKD patients and correlate with the severity of kidney disease. The prevalence of both anterior and posterior segment abnormalities underscores the need for regular ophthalmic evaluations in CKD patients to prevent vision loss and manage ocular complications early.

Using Chronic Kidney Disease as a Model Framework to Estimate Healthcare-Related Environmental Impact.

While the economic and clinical burden of chronic diseases are well documented, their environmental impact remains poorly understood. We developed a framework to estimate the environmental impact of a disease care pathway using chronic kidney disease (CKD) as an example. A life cycle assessment framework was developed for the CKD care pathway and validated by experts. Life cycle stages were characterised for resource utilisation based on a literature review and ecoinvent database inputs, in ten countries. The ReCiPe impact assessment method was used to calculate impacts across multiple environmental dimensions. At CKD stage5, kidney replacement therapies (KRT) have highest impact; emissions ranged between 3.5 and 43.9kg carbon dioxide equivalents (CO2e) per session depending on dialysis modality, and 336-2022kgCO2e for kidney transplant surgery, depending on donor type. Hospitalisations have a substantial environmental impact: a 1-day intensive care stay had highest impact (66.4-143.6kgCO2e), followed by a 1-day hospital stay (28.8-63.9kgCO2e) and an 8-h emergency room visit (14.4-27.5kgCO2e). Patient transport to and from healthcare sites was a key driver of environmental impact for all life cycle stages, representing up to 99.5% of total CO2e emissions. Full care pathways should be analysed alongside specific healthcare processes. Application of this framework enables quantification of the environmental benefits of preventative medicine and effective management of chronic diseases. For CKD, early diagnosis, and proactive management to reduce the need for KRT and hospitalisations could improve patient outcomes and reduce environmental burden.

Use of Aspirin and Initial Cardiovascular and Bleeding Risk in Patients with Chronic Kidney Disease

Background: Despite the high cardiovascular risk in patients with chronic kidney disease (CKD), the role of aspirin in primary prevention remains unclear. This study aimed to investigate the association between aspirin initiation in adults with CKD without prior cardiovascular disease (CVD) and the first cardiovascular and bleeding events using Korean nationwide cohort data. Methods: Among individuals aged 40–79 years with an estimated glomerular filtration rate between 15 and 59 mL/min/1.73 m2 who underwent routine health examinations between 2011 and 2016, 15,861 individuals who were newly prescribed aspirin at a dose of 100 mg/day were matched with 79,305 aspirin non-users by propensity score matching. The primary efficacy outcome was a composite of nonfatal atherosclerotic CVD or cardiovascular death. The primary safety outcome was hospitalization due to intracranial or gastrointestinal bleeding. Results: During a mean follow-up of 6.9±2.9 years, the incidence rates for the primary efficacy outcome in aspirin users and non-users were 8.0 and 9.0 per 1,000 person-years, respectively. Aspirin therapy initiation was not associated with the primary efficacy outcome (hazard ratio [HR], 0.93; 95% confidence intervals [CI], 0.86-1.04). However, the primary safety outcome of major bleeding was more frequent in aspirin users than in non-users (6.7 versus 4.7 per 1,000 person-years). The HR for this outcome in aspirin users versus non-users was 1.45 (95% CI, 1.32-1.59). Conclusions: No association was observed between aspirin use and the risk of nonfatal atherosclerotic CVD or cardiovascular death in patients with CKD stages G3 and G4 without prior CVD. Aspirin use was associated with higher risk of major bleeding.

Clinical characteristics and prognosis of steroid-resistant nephrotic syndrome in children: a multi-center retrospective study.

This study investigated the factors influencing the prognosis of children with steroid-resistant nephrotic syndrome (SRNS) in patients from the Guangxi region. We retrospectively analyzed clinical and pathological data of 279 patients with SRNS from six tertiary hospitals in Guangxi. Clinical data were compared between initial (I-SRNS) and secondary (S-SRNS) steroid resistance subgroups and Cox regression analysis was used to determine risk factors for chronic kidney disease (CKD) and CKD stage 5 (CKD5) in patients with SRNS. The median age of onset was 54 months. Thirty-three patients had extra-kidney manifestations. Fifty-two, 24, 57, 33, and 41 patients had hypertension, acute kidney injury, vitamin D deficiency, high intraocular pressure, and dwarfism, respectively. One hundred eighty-two and 92 patients had I-SRNS and S-SRNS, respectively. There were significant differences in sex, ethnicity, family history, incidence of hematuria, clinical classification, efficacy of immune agents, and prognosis between groups (P < 0.05). Among the 279 cases of SRNS, 239 had normal kidney function, 37 developed CKD, and 16 had CKD5. An increase in serum creatinine level (HR = 1.003) was significantly associated with CKD in children with SRNS, and effective immunosuppressant therapy decreased the CKD risk (HR = 0.168). Patients with increased serum creatinine levels (HR = 1.003) and acute kidney injury (HR = 4.829) were more likely to progress to CKD5. Children with S-SRNS showed a higher response to immunosuppressants than those with I-SRNS. Effective immunosuppressant therapy was found to protect against CKD, whereas increased acute kidney injury was an independent risk factor for CKD5.

Relationship between exercise habits and social isolation in older patients with predialysis CKD: a cross-sectional study

Abstract Background Maintaining exercise habits in older patients with predialysis chronic kidney disease (CKD) is important to prevent conversion to renal replacement therapy and improve prognosis. This study identified factors influencing exercise habits in older patients with predialysis CKD. Methods This cross-sectional study included 113 patients aged ≥ 65 years with stages 3–5 predialysis CKD who were admitted for CKD education purposes. Exercise habits were assessed using the transtheoretical model. Social isolation was assessed using the Lubben Social Network Scale (LSNS-6). Furthermore, the short physical performance battery (SPPB) and grip strength, exercise self-efficacy (SE), hemoglobin, and estimated glomerular filtration rate of the participants were assessed. Results Among the 55 patients who maintained exercise habits, 20 (57.1%) were at CKD stage 3, 19 (43.2%) were at CKD stage 4, and 16 (47.1%) were at CKD stage 5. The LSNS-6, SPPB, grip strength, and exercise SE scores significantly differed between the with exercise habits group and without exercise habits group (p &lt; 0.05). The multivariate logistic regression analysis results indicated that the LSNS-6 (OR:1.10; 95%CI:1.022–1.210) and exercise SE (OR:1.10; 95%CI:1.009–1.199) were significantly associated with exercise habits (p &lt; 0.05). Conversely, no significant associations were found between exercise habits and SPPB, grip strength, renal function, or anemia. Conclusions Social isolation and SE may be an important factor influencing exercise habits in older patients with predialysis CKD.

The effect of sevelamer on serum calcification propensity in patients with chronic kidney disease: the results of a multicentre, double-blind, placebo-controlled, randomized clinical trial

Abstract Background The serum calcification propensity test (or T50 test) might become a standard tool for the assessment of vascular calcification risk, and T50 might be a valuable biomarker in clinical trials of treatments intended to slow the progression of vascular calcification. Literature data suggest that non-calcium-containing phosphate binders can influence T50 in chronic dialyzed patients. However, it is not clear whether similar interventions are effective in patients at earlier stages of chronic kidney disease (CKD). Methods The “FGF23 Reduction efficacy of a new Phosphate Binder in CKD” (FRENCH) trial was a multi-centre, double-blind, placebo-controlled, randomized trial of sevelamer carbonate in participants with stage 3b/4 CKD. In this subanalysis of the FRENCH data, T50 and other laboratory variables (including fetuin A, and ionized and total magnesium) were measured centrally at baseline and after 12 weeks of treatment. Results A total of 96 patients were screened; 78 (55 men and 23 women) met the inclusion criteria and were randomized to receive placebo (n=39) or sevelamer carbonate (n=39). The median [interquartile range] patient age was 66 [56-72], the median eGFR was 25 [21-30] mL/min/1.73m², and the mean T50 was 335 (82) minutes. In a linear regression model, T50 was independently associated with serum ionized magnesium, fetuin-A and bicarbonate levels; and inversely associated with phosphate concentration. The within-group changes in the mean [95% confidence interval] T50 between week 0 and week 12 were not significant in the sevelamer group or the placebo group (4.6 [-13.6; 22.8] minutes (p=0.61) and 7.8 [-16.4; 32.1] minutes (p=0.51), respectively). Furthermore, we did not observe significant changes in fetuin-A and magnesium levels. Conclusion A 12-week course of the non-calcium-containing phosphate binder sevelamer carbonate was not associated with a significant change in T50 in patients with stage 3b/4 CKD. Phosphate binders might not be an effective strategy for modifying serum calcification propensity in non-dialysis-dependent patients with CKD.

PREVALENCE, Characteristics, and Awareness of Chronic Kidney Disease in Croatia: The EH-UH 2 Study

Background. National surveys have reported variable prevalence of chronic kidney disease (CKD), due to differences in the characteristics of the population, study design, equations used for the estimated glomerular filtration rate (eGFR), and definitions. The EH-UH 2 survey is the first study evaluating CKD prevalence, characteristics, and awareness in Croatia. Methods. This was a cross-sectional nationwide observational study designed to assess the prevalence of CKD and cardio–kidney–metabolic risk factors in Croatia, which included 1765 randomly selected subjects. We estimated the prevalence of CKD by means of the albumin-to-creatinine ratio (ACR) and eGFR (CKD-EPI equation). Comorbidities and anthropometric and social factors related to the prevalence of CKD were analyzed, and the CV risk profile was evaluated. Results. The weighted prevalence of CKD (any stage), CKD stage ≥G3A A2, and CKD defined only as an eGFR &lt;60 mL/min/1.73 m2 were estimated at 17.1%, 9.8%, and 7.9%, respectively. The prevalence was higher in men than in women (11.8% vs. 7.9%; p &lt; 0.001). The weighted prevalence of an ACR &gt;30 mg/g was 15.1%. Older age, male gender, diabetes, ePWV, and uric acid were independently associated with CKD prevalence. The awareness of CKD was 9.5%. Persons unaware of CKD were older with lower income, less education, more frequent diabetes, hypertension (less frequently controlled), and milder renal impairment. Conclusions. In Croatia, the estimated prevalence of CKD is high, being presented more frequently in men than in women. CKD patients have an unfavorable CV risk profile. The awareness of CKD is very low, reflecting poor health literacy in the general population but also in health-care workers.

Primary glomerular diseases and long-term adverse health outcomes: A nationwide cohort study.

Although glomerular diseases are the third most frequent cause of end-stage kidney disease worldwide, little is known about their long-term outcomes. In patients with chronic kidney disease (CKD) stage 3-5 enrolled in the Swedish Renal Registry, we compared risks of hospitalization, kidney replacement therapy (KRT), major cardiovascular events (MACE), and death of the four most frequent primary glomerular diseases (IgA nephropathy [IgAN], focal segmental glomerulosclerosis [FSGS], minimal change disease [MCD], and membranous nephropathy [MN]), and patients with CKD due to the most common non-communicable diseases (control-CKD). We identified 2396 patients with glomerular disease (97% biopsy-proven, 69% men, 57 years, eGFR 29mL/min/1.73m2, uACR 88mg/mmol, 1524 with IgAN, 398 FSGS, 94 MCD, and 380 MN) and 37,697 controls (64% men, 74 years, eGFR 25mL/min/1.73m2, uACR 23mg/mmol), mainly with diabetic nephropathy and nephroangiosclerosis. The median follow-up was 6.3 (3.3; 9.9) years. Compared with control-CKD, patients with primary glomerular diseases generally had a lower risk of hospitalization, MACE (adjusted hazard ratios [HRs] ranging from 0.44 to 0.88 depending on the etiology) and death (HRs ranging 0.45-0.76). Patients with IgAN and FSGS had a faster eGFR decline and a higher rate of KRT (HRs 1.26 [95%CI: 1.15-1.37] and 1.34 [1.15-1.57], respectively). Conversely, patients with MN and MCD had a lower KRT rate and slower eGFR decline. Despite having a lower relative risk of hospitalization, cardiovascular events and mortality, patients with IgAN and FSGS are at higher risk of CKD progression than the most common etiologies of CKD, emphasizing the need for more stringent treatment strategies in these patients.

Abstract 4134637: Impact of Glucagon-Like Peptide-1 Agonists on Cardiovascular Outcomes in Chronic Kidney Disease Stage 5: A Propensity Score-Matched Analysis

Background: Patients with chronic kidney disease stage 5 (CKD-5) face heightened risks of cardiovascular (CV) complications and mortality. Glucagon-like peptide-1 agonists (GLP-1a), primarily used in type 2 diabetes, are being investigated for potential CV benefits in this population. This study aims to evaluate the impact of GLP-1a treatment on CV outcomes and survival among CKD-5 patients. Methods: This retrospective cohort study utilized data of adult patients diagnosed with CKD-5 between January 2014 and August 2023 from the TriNetX global research network. A propensity score matching analysis of those treated with GLP-1a for at least six months versus those never exposed to GLP-1a therapy was conducted. Results: Our analysis showed significantly reduced odds for the composite primary outcome of acute myocardial infarction (AMI), stroke, and mortality (OR = 0.66, 95% CI: 0.57-0.78, p&lt;0.001), and other CV outcomes such as cardiac arrest, hypertensive crisis, and hypertensive urgency, among the GLP-1a cohort compared with the non-GLP-1a cohort. Kaplan-Meier survival analysis revealed a significantly higher five-year incidence-free probability for the composite primary outcome (63.5% vs. 50.5%, p&lt;0.001) and for other CV outcomes such as hypertensive events, AMI, cardiac arrest, and hemorrhagic stroke for the GLP-1a cohort. Conclusion: The study suggests that GLP-1a therapy in CKD 5 patients may confer certain CV benefits. Further investigations are warranted to elucidate the underlying mechanisms and confirm the therapeutic efficacy of GLP-1a in this patient population.

Abstract 4144567: Prevalence of Atrial Fibrillation in Amyloidosis and Their Association: A 5-Year Nationwide Analytical Cross-Sectional Study

Background: Atrial fibrillation (AF) is a common cardiac arrhythmia associated with significant morbidity and mortality. Amyloidosis (AM) is characterized by the accumulation of amyloid protein in various anatomical sites, including the heart, atria, and ventricles. This amyloid infiltration leads to adverse chamber remodeling, predisposing patients to tachyarrhythmias such as atrial fibrillation/flutter. This study aims to re-evaluate the association of AM with AF by using the large nationwide inpatient database over a total duration of 5 years. Methods: An analytical cross-sectional study was conducted utilizing the data from a survey-weighted national inpatient sample database covering admissions from Jan 2017 to Dec 2021. A total of 147,015,073 admissions of patients aged 18 years and above were included. Descriptive statistics and univariate logistic regression models were used to calculate prevalence rates and odds ratios (OR), respectively. The multivariate logistic regression model was then used to adjust various potential confounders, including age, gender, race, income, hypertension, diabetes, stage 3 or above chronic kidney disease (CKD), Charlson comorbidity index, and hospital-related factors. Results: The 5-year prevalence of AF was 36.73% and 15.42% in admissions with and without AM, respectively. Significant differences between the with AM and without AM groups were in mean ages (72.40 vs. 58.08), female (41.83% vs. 56.92%), race of Black (24.57% vs. 15.40%), and CKD stage 3+ (44.83% vs. 16.65%), respectively. The univariate logistic regression analysis showed an OR for AF of 3.18 (95%CI: 3.102 - 3.267, P&lt;0.000) in admissions with AM compared to those without. After adjustment for the potential confounders, the OR for AF decreased to 1.64 (95%CI 1.597- 1.686; P&lt;0.000) in patients with Amyloidosis compared to those without. Conclusion: This study confirms a significant association between amyloidosis and atrial fibrillation, demonstrating that patients with amyloidosis have a markedly higher prevalence of atrial fibrillation compared to those without. Univariate analysis showed an odds ratio of 3.18 for atrial fibrillation in amyloidosis patients, which remained significantly elevated at 1.64 after adjusting for confounders. These findings indicate the need for a comprehensive workup of suspected atrial fibrillation in amyloidosis patients. Further research should investigate the mechanisms behind this association and potential prevention.

Abstract 4134333: Blood pressure reduction in diabetic patients with resistant hypertension: results from the aprocitentan PRECISION study

Background: In patients with resistant hypertension (RHT), diabetes is a frequent comorbidity that increases the risk of cardiovascular events. The phase-3 PRECISION study demonstrated the efficacy of aprocitentan (APRO), a dual endothelin ET A /ET B receptor antagonist, to lower blood pressure (BP) in patients with RHT. In this pre-planned PRECISION post hoc analysis, we evaluated the BP lowering effect of APRO in diabetic patients. Methods: Eligible patients were hypertensive despite treatment with ≥3 antihypertensive medications from different classes. After ≥4 weeks of combination therapy (amlodipine/valsartan/hydrochlorothiazide), patients still hypertensive received single-blind placebo for a run-in period, followed by a 4-week double-blind part (APRO 12.5 mg, 25 mg, or placebo), a 32-week single-blind part (APRO 25 mg) and a 12-week double-blind withdrawal part (APRO 25 mg or placebo). The primary endpoint was change from baseline to Week 4 in mean trough office SBP. Results: Out of 730 patients, 395 (54%) had diabetes (APRO 12.5 mg, n=112; 25 mg, n=107; placebo, n=116). At Week 4, APRO reduced office SBP (12.5 mg: −14.6; 25 mg: −14.1 mmHg) vs placebo (−9.4 mmHg) in diabetic patients, with no treatment/diabetes status interaction (p=0.77). The reduction was maintained at Week 36 (−16.2 mmHg). APRO also reduced mean 24-hour ambulatory SBP at Week 4 (12.5 mg: −7.4 mmHg; 25 mg: −9.5 mmHg) vs placebo (−2.2 mmHg), most pronounced on night-time values (12.5 mg: −8.9 mmHg; 25 mg: −13.1 mmHg; placebo: −1.6 mmHg). At Week 40, after 4 weeks of withdrawal, office SBP increased in placebo patients (+3.6 mmHg) and remained stable with APRO 25 mg (+0.2 mmHg). A substantial reduction in urine albumin–creatinine ratio of 33% and 37% was observed at Week 4 for APRO 12.5 mg and 25 mg, respectively, compared with an increase of 11% for placebo. Edema/fluid retention were the most common adverse events; they were mild-to-moderate in most cases and dose dependent (9%, 23%, and 2% of patients receiving APRO 12.5 mg, 25 mg, and placebo, respectively, up to Week 4). During the study, 11 patients were hospitalized for heart failure (10 treated with APRO 25 mg and one with placebo). Among these, 6 had chronic kidney disease stage 3–4, and 5 had medical history of heart failure; no cases were fatal. Conclusion: APRO produced clinically relevant and sustained BP reduction in diabetic patients with RHT, consistent with the effect observed in the overall population.

Abstract 4117180: Hyperkalemia-Related Hospitalization Associated with Short-Term vs. Long-Term Outpatient SZC Therapy Among RAASi Users: The GALVANIZE Outcome study

Introduction: Patients receiving renin-angiotensin-aldosterone system inhibitors (RAASi) are at increased risk of developing hyperkalemia (HK). Sodium zirconium cyclosilicate (SZC) is used to treat HK, but the impact of duration of SZC on healthcare resource utilization (HRU) in RAASi users is unknown. The GALVANIZE Outcome study compared HK-related HRU among RAASi users between long-term and short-term SZC users. Methods: Adults with ≥1 outpatient prescription for SZC (index date) and ≥1 RAASi prescription spanning the index date were identified from a large US insurance claims database (7/2018-12/2022) and were stratified based on duration of SZC use. Long-term SZC users (&gt;90 days) and short-term SZC users (≤30 days) were exactly and propensity score matched on key baseline characteristics. Rates of HK-related hospitalizations or emergency department (ED) visits, HK-related ED visits, and HK-related hospitalizations were compared during follow-up from index to the earliest of 6 months post-index, end of data availability, other potassium binder use, or re-initiation of SZC post-discontinuation. Results: Among 1,586 matched pairs, the mean age was 65.5 years, 41.0% of patients were female, and most patients had any stage chronic kidney disease (91.9%), hypertension (90.8%), and diabetes (73.4%). Also, 30.0% of patients had heart failure. The most used RAASi therapies at index were angiotensin-converting enzyme inhibitors (57.3%) and angiotensin-receptor blockers (56.3%). Patients with long-term SZC use had a 44% lower rate of HK-related hospitalizations or ED visits, a 41% lower rate of HK-related hospitalizations and a 52% lower rate of HK-related ED visits than patients with short-term SZC use during follow-up (all p&lt;0.01; Figure 1). Conclusions: Among patients with RAASi and SZC therapy use, long-term SZC use was associated with significantly lower rates of HK-related HRU compared to matched patients with short-term SZC use. Funding: AstraZeneca

Abstract 4132409: Caspase-4/11 promotes a high-fat diet and chronic kidney disease-accelerated vascular inflammation via caspase-4/11-IL-1b two-tier trained immunity

Introduction: Chronic kidney disease (CKD) is a common inflammatory disease affecting &gt;15% of the adult population and 50% of all patients with advanced/end stages (4 to 5) of CKD have cardiovascular disease. Research Questions: How multiple disease risk factors interplay to accelerate vascular inflammation in CKD. Aim: To determine whether hyperlipidemia and CKD have a synergy in accelerating vascular inflammation via trained immunity (TI). Methods: we performed aortic pathological analysis and RNA-sequencing in high-fat diet (HFD)-fed 5/6 nephrectomy CKD (HFD+CKD) mice. Results: 1) HFD+CKD increases aortic cytosolic lipopolysaccharide (LPS) levels, caspase-11 (casp11) activation, and 998 gene expressions of TI pathways in the aorta (first-tier TI mechanism); 2) Casp11 —/— decreases aortic neointima hyperplasia, aortic recruitment of macrophages, and casp11-gasdermin D-mediated cytokine secretion; 3) Casp11 —/— decreases N-terminal gasdermin D (N-GSDMD) membrane expression on aortic endothelial cells and aortic IL-1b levels; 4) LPS transfection into human aortic endothelial cells results in casp4 (human)/casp11 (mouse) activation and increases N-GSDMD membrane expression; 5) IL-1b serves as the second-tier mechanism underlying HFD+CKD-promoted TI. Conclusion: Hyperlipidemia and CKD accelerate vascular inflammation by promoting two-tier trained immunity

Patient-reported outcome measures for life participation in patients with chronic kidney disease: a systematic review

Abstract Background The symptoms, comorbidities and treatment burden associated with chronic kidney disease (CKD) can be debilitating and limit life participation in patients with CKD not requiring kidney replacement therapy (KRT). The aim of this study was to identify the characteristics, content, and psychometric properties of patient-reported outcome measures (PROMs) used to assess life participation in patients with CKD. Methods We searched MEDLINE, Embase, PsycINFO, and CINAHL from database inception to February 2023 for all studies that reported life participation in patients with CKD (Stage 1–5 not requiring kidney replacement therapy). We analyzed the characteristics, dimensions of life participation and psychometric properties of the measures. Results From the 114 studies included, 20 (18%) were randomized trials, 3 (3%) were non-randomized trials, and 91 (80%) were observational studies. Forty-one different measures were used to assess life participation, of which six (15%) were author-developed measures. Twelve (29%) measures assessed life participation specifically, while 29 (71%) measures assessed broader constructs such as quality of life, which included questions relevant to life participation. The 36-Item Short Form Health Survey (SF-36) and Kidney Disease Quality of Life—Short Form (KDQOL-SF) were the most frequently used, in 39 (34%) and 24 (21%) studies, respectively. Many content domains for life participation were assessed including physical activities (walking, running, and sports), social activities, leisure activities, work or study and self-care. None of the measures for life participation were developed specifically for CKD. Four measures (EQ-5D-3 L, FACT-An, SF-6D, and SF-36) had validation data collected in patients with CKD. Conclusion The measures for life participation used in patients with CKD vary in content with few validated in the CKD population. There is a need for a validated measure to assess life participation in a meaningful and consistent way in all patients with CKD worldwide.

Correlation between Fundus Damage and Renal Function Deterioration in Chronic Kidney Disease Patients.

This study aimed to explore the correlation between the extent of fundus damage and the severity strategies for chronic kidney disease (CKD). We collected data from 118 CKD patients, including general information, renal function indicators, and fundoscopic examination results. The stages of CKD and degrees of fundus lesions were graded. SPSS 25.0 software facilitated the analysis of correlations using Kendall's tau-b correlation analysis and ordinal regression analysis. Statistically significant differences were observed among multiple CKD stages in the distribution of age, systolic blood pressure, diastolic blood pressure, hemoglobin, total cholesterol, homocysteine, cystatin C, serum creatinine, blood urea, eGFR, 24-hour urine protein, urine microalbumin, urine microalbumin/urine creatinine, and blood β2 microglobulin, complement C3. Notably, the levels of cytokeratin 19 fragment and transforming growth factor β significantly increased in all CKD stages. Kendall's tau-b correlation analysis revealed a significant positive correlation between CKD stage and fundus lesion grade. Ordinal regression analysis indicated that sex differences, total cholesterol levels, and hemoglobin levels were significant predictors of fundus lesion risk. Compared with patients at stage 5 CKD, the risk of fundus damage significantly lower in patients in stage 2 and stage 3, further demonstrating a positive correlation between renal function deterioration and increased risk of fundus damage. Routine fundus screening and early intervention for fundus lesions are vital for assessing CKD deterioration, providing new directions for future related research.

Burden of Kidney Disease in an Aging Population Living with HIV in the United States.

Antiretroviral therapy (ART) has significantly improved mortality rates for individuals living with HIV, but kidney disease remains prevalent, especially among older adults. Our study analyzed the burden of kidney disease in individuals aged 65 and older at The Miriam Hospital Immunology Center in Rhode Island. We calculated estimated glomerular filtration rates using the last creatinine values from 2019 and identified chronic kidney disease (CKD) stages. Results showed a 19% prevalence of moderate or severe CKD among adults living with HIV, rising to 39% for those aged 75 and older. Particularly striking was the increased prevalence among African American adults aged 65+, at 30.4%, rising to 50% for those over 75. In comparison, the National Institute of Diabetes and Digestive and Kidney Diseases reports that CKD stage 3 affects 20.1% of adults aged 65+, compared with just 1.2% in those younger than 65. Gender and racial disparities are evident; CKD stage 3 is more prevalent in females (5.8%) than males (4.4%). Our findings indicate that 32% of HIV-positive females have moderate-to-severe kidney disease, compared with 14% of males. Importantly, we did not account for hypertension, diabetes, and hepatitis C virus infection, which may influence renal outcomes. Our study shows that ART has reduced mortality, as more people with HIV now live longer, while also revealing the disproportionate burden of kidney disease among older adults and racial minorities, as well as a concerning trend among women; therefore, emphasizing the need for targeted health care strategies for high-risk groups.

Sodium-chloride difference is not strongly correlated with base excess in chronic kidney disease: an anion gap problem.

The prevalence of metabolic acidosis is high in patients with chronic kidney disease (CKD). For the diagnosis, a blood gas analysis is necessary, but not always available. The aim of the study was to evaluate the base excess (BE) of the sodium-chloride difference (BENa-Cl = Na+-Cl--34mmol/l) as a screening parameter for hyperchloremic metabolic acidosis. We retrospectively performed acid-base analyses of 168non-dialysedpatientswith CKDaccording to the physiologic and to the Stewart's approach. We performed linear regression analysis, Bland-Altman plot and receiver operating characteristics (ROC) analysis of BENa-Cland BE to evaluate the accuracy of BENa-Clpredicting the BE. We further investigated possible confounding factors. The corrected R2for the correlation of BENa-Cland BE was 0.60 (p < 0.001). The Bland-Altman plot showed a good overall agreement. The bias was negligible, but the 95%-limits of agreement showed a wide interval (10.4mmol/l). For BE ≤ 2mmol/l, the ROC analysis yielded an AUC of 0.89 and moderate sensitivity (0.75) and specificity (0.86) for the optimal BENa-Clthreshold (≤ 2mmol/l). Subgroup analysis showed similar results. The main factor for the imprecision of BENa-Clpredicting the BE across all stages of CKD is the variability of the serum anion gap (SAG). The BENa-Clis not an adequate parameter for screening of hyperchloremic acidosis because of the high variability of the SAG. Only, if the BENa-Clis ≤ 5mmol/l, a hyperchloremic acidosis should be suspected. Therefore, a complete blood gas analysis is necessary for the correct diagnosis of acid-base disorders in patients with chronic kidney disease.

Computational and Human Intelligence Methods for Constructing Practical Risk Prediction Models: An Application to Cardio-Renal Outcomes in Non-Diabetic CKD Patients

AbstractThe current investigation aimed to develop a novel approach for risk prediction modeling of clinical outcomes in common diseases based on computational and human intelligence techniques with no a priori input on risk factors using real-world individual patient-level data from administrative claims. Bootstrapping multivariable Cox regression and ant colony optimization were employed to develop time-to-first-event risk prediction models of cardio-renal outcomes in patients with non-diabetic chronic kidney disease (CKD) as a demonstration case. A cohort of 504,924 non-diabetic CKD stage 3 or 4 patients enrolled from 2008 to 2018 were identified in the US administrative de-identified claims database, Optum Clinformatics® Data Mart. Initial set of potential risk factors was derived from patient-level data at baseline and included more than 540,000 variables. Risk prediction models of hospitalization for heart failure, worsening of CKD stage from baseline and a renal composite outcome of end-stage kidney disease, kidney failure or need for dialysis in non-diabetic CKD stage 3 or 4 were built. Final model optimization was conducted using human intelligence to combine clinically similar features and build equivalence classes to ensure that risk factors included in the final model were routinely collected and easily interpretable by healthcare providers. Demonstrated validity of our approach in non-diabetic CKD offers opportunities for application in other therapeutic areas, with the potential to improve overall prognosis and decrease the clinical and economic burden of common diseases. The approach enables developing practical prediction models for risk estimation in routine clinical practice.