Severe Chronic Kidney Disease Research Articles

Percutaneous endoscopic gastrostomy in children receiving peritoneal dialysis: A tertiary centre long-term experience and literature review.

Children with severe chronic kidney disease receiving maintenance peritoneal dialysis (PD) are often malnourished and may require nutritional supplementation. Recent PD guidelines address laparoscopic and open surgical gastrostomy as safe approaches in children established on PD, while existing evidence on percutaneous endoscopic gastrostomy (PEG) is still lacking; as well as the role of perioperative antibiotic and antifungal prophylaxis. Hence, this study aimed to report our experience with PEG placement in patients on PD and compare it with the available literature. We retrospectively reviewed the medical records from patients on PD, who underwent PEG placement at a tertiary referral centre between 2000 and 2020. Data on perioperative management, complications and outcomes were retrieved. An extensive literature search was performed; studies describing PEG placement and perioperative prophylaxis in patients on PD were used as a comparison. Descriptive statistical analysis was conducted. Seven patients (five males) were included. Perioperative antibiotic and antifungal prophylaxis were standard practice. At a median follow-up of 27 months (10-75), the peritonitis rate was 0.2 patient/years. No statistical significance was found between the peritonitis rate before and after PEG placement (p = 0.2). Patients' demographics and postoperative complications were comparable to the reported studies. Based on our experience, our technique of PEG insertion with antimicrobial prophylaxis is feasible and associated with an acceptable complication risk in patients on PD. Further multicentric studies about surgical technique in patients on PD will be necessary to verify the feasibility of PEG and standardise the perioperative protocol.

Association between prevalence and severity of chronic kidney disease and employment status: a nationwide study in Korea.

The prevalence of chronic kidney disease (CKD) is increasing globally, and understanding the association between CKD and employment status is crucial. This cross-sectional study aimed to investigate the association of CKD with employment and occupation type among patients with CKD. We analyzed data from 36,732 Korean adults aged ≥ 30 years, who participated in the Korean National Health and Nutrition Examination Survey between 2014 and 2021. CKD was detected based on the estimated glomerular filtration rate, and the employment status of the participants was classified into distinct categories: full-time permanent employment, unemployment, self-employment, and precarious employment. We analyzed the data using multiple logistic regression. We observed a significant association between CKD and a higher likelihood of unemployment compared to that in individuals without CKD (odds ratio, 1.70; 95% confidence interval, 1.47-1.96). This association was more prominent in patients with severe CKD. In the multivariable logistic analysis, patients with CKD had a higher likelihood for precarious employment (odds ratio, 1.29; 95% confidence interval, 0.92-1.88), self-employment (odds ratio, 1.3; 95% confidence interval, 0.90-1.88), and unemployment (odds ratio, 2.10; 95% confidence interval, 1.51-2.92) compared to individuals without CKD. Our study demonstrated that CKD is associated with a higher likelihood of unemployment and engagement in precarious employment. These findings highlight the challenges faced by patients with CKD in obtaining stable employment and emphasize the need for interventions to improve the employment outcomes of individuals with CKD.

Safety and efficacy of colchicine in crystal-induced arthritis flare in 54 patients with severe chronic kidney disease

IntroductionColchicine, commonly used in gout flare, is contraindicated in severe chronic kidney disease (CKD) (estimated glomerular filtration rate <30 mL/min). However, in this context, there are few alternatives, and colchicine...

Exploring dyslipidemia and cardiovascular morbidity in chronic kidney disease patients: A cross-sectional study

ABSTRACT Introduction: Chronic kidney disease (CKD) is a prevalent health concern with significant implications for patient health. This study investigates the relationship between dyslipidemia and cardiovascular morbidity in CKD patients. CKD is characterized by kidney damage, reduced glomerular filtration rate, and is associated with various complications, including cardiovascular disease. Dyslipidemia, characterized by abnormal lipid levels, is common in CKD patients and contributes to the development of atherosclerosis and cardiovascular complications. Materials and Methods: This 1-year cross-sectional observational study was conducted at a tertiary care center in northern India. The study included 160 patients aged 16 and above who had been diagnosed with CKD. Researchers conducted a comprehensive analysis of lipid profiles in these patients and assessed cardiovascular morbidity through a review of clinical records. Results: In our study, we observed that 96 out of 160 patients diagnosed with CKD exhibited lower than recommended levels of high-density lipoprotein (HDL). Furthermore, in patients with CKD Stages IV and V, low-density lipoprotein (LDL) cholesterol (LDL-C) levels were notably elevated. Triglyceride levels (TGs) were consistently elevated across the board in our study. Specifically, the mean TGLs were 159, 162.8, 211, and 246.8 in CKD Stages II, III, IV, and V, respectively, which was statistically significant. In addition, total cholesterol levels were found to be elevated in 110 out of 160 patients within our study group. Most of the patients with CKD were found to have systolic or diastolic dysfunction on two-dimensional echocardiography. Furthermore, associated coronary artery disease was higher in Grade III and Grade V CKD patients. The study yielded several notable findings regarding cardiovascular morbidity in CKD patients. Cardiovascular morbidity was observed in a significant proportion of CKD patients, highlighting the strong link between CKD and heart-related complications. Abnormal lipid profiles, such as low levels of HDL and elevated levels of LDL-C, were prevalent in CKD patients with cardiovascular morbidity. An association between the severity of CKD, as determined by Stage, and the presence of cardiovascular morbidity was evident. Patients with advanced CKD Stages (IV and V) were more likely to exhibit cardiovascular complications. Dyslipidemia, particularly elevated TGLs, was implicated as a potential contributor to cardiovascular morbidity in CKD patients. Conclusion: This study underscores the significance of cardiovascular morbidity in CKD patients and its association with dyslipidemia. Findings suggest that early diagnosis and management of dyslipidemia are essential for mitigating the long-term cardiovascular consequences in CKD patients. Health-care providers should be vigilant in monitoring lipid profiles in CKD patients and implementing appropriate interventions to reduce their risk of cardiovascular complications. By integrating the study’s findings on cardiovascular morbidity with dyslipidemia in CKD patients, health-care practitioners can better understand the multifaceted nature of this condition and tailor their treatment strategies accordingly.

Initiation patterns of anticoagulants for atrial fibrillation among older UK adults with and without chronic kidney disease, 2010–2020

BackgroundThere is a paucity of data on the initiation patterns of anticoagulants among older atrial fibrillation patients with and without chronic kidney disease (CKD).Setting and methodsWe used the UK Clinical...

Vitamin D Levels among Chronic Kidney Disease Patients at a Tertiary Care Hospital: A Cross-sectional Study

Introduction: In patients with Chronic Kidney Disease (CKD), a high prevalence of metabolite abnormalities has been observed. Numerous studies have demonstrated that individuals with reduced Glomerular Filtration Rate (GFR) are more susceptible to severe vitamin D deficiency compared to those with normal kidney function. Aim: To investigate the association between vitamin D levels and the severity of CKD among patients at Siddhartha Medical College, GGH in Vijayawada, Andhra Pradesh, India. Materials and Methods: The present hospital-based cross- sectional study was conducted at Siddhartha Medical College, GGH, Vijayawada, Andhra Pradesh, India from December 2021 to February 2022. A total of 100 CKD patients with a GFR of less than 60 mL/min/1.72 m2 were included in the study. Vitamin D levels were assessed using Chemiluminescence immunoassay (Access 2, Beckman Coulter), and vitamin D deficiency was defined as 25-OH vitamin D levels of less than 10 ng/mL, while insufficiency was defined as levels between 10 to 30 ng/mL. Statistical analysis was performed using Analysis of Variance (ANOVA) test and Pearson’s correlation test. Results: The mean age of the study population was 53.25±7.6 years, with the majority (32%) belonging to the 51-60 years age group. In terms of gender distribution, approximately three-fourths (72%) of the subjects were male. Hypertension was present in 44% of CKD patients, diabetes in 38%, and cardiovascular disease in 38%. Total 53% of CKD patients were classified as stage 4 on the Kidney Disease: Improving Global Outcome (KDIGO) CKD staging. Vitamin D deficiency was observed in 26% of patients, while 39% had insufficiency. A statistically significant association was found between the severity of CKD staging and mean vitamin D levels, with lower mean levels observed in stages 4 and 5. Conclusion: Vitamin D deficiency was present in one-fourth of the CKD patients, and it was more pronounced in advanced stages of CKD.

The Role of Uromodulin in Chronic Kidney Disease – A Systematic Review and Meta-Analysis

Background: Numerous studies have investigated the function of the biomarker uromodulin (UMD), which has shown promise in the diagnosis and severity assessment of chronic kidney disease (CKD). However, the results continue to be contradictory and inconclusive. Consequently, our goal was to investigate the connection between UMD and CKD patients, with a focus on their diagnostic utility and association with the severity of CKD based on the Kidney Disease Improving Global Outcomes (KDIGO) classification. Methods: We systematically searched PubMed, EMBASE, and Scopus using a predefined string to identify relevant studies. Included studies diagnosed CKD based on GFR according to Kidney Disease Outcomes Quality Initiative KDOQI guidelines or by calculating eGFR using the MDRD formula, meeting predefined criteria. Quality assessment was conducted using the Newcastle Ottawa Scale (NOS). The main outcome was the mean difference (MD) in serum UMD levels across CKD stages. Results: A total of 5 articles involving 1,094 subjects fulfilled our inclusion criteria and were included in our systematic review and meta-analysis. Significant differences in UMD levels were observed across multiple comparisons. When comparing CKD patients to controls, UMD levels showed a substantial MD of –115.719 (95% CI –163.297, -68.141). Similarly, UMD levels exhibited significant MDs when comparing controls vs. CKD 1 71.185 (95% CI 39.572, 102.798), controls vs. CKD 2 81.531 (95% CI 40.570, 122.491), controls vs. CKD 3 130.886 (95% CI 99.095, 162.677), controls vs. CKD 4 180.317 (95% CI 141.373, 219.262), controls vs. CKD 5 198.033 (95% CI 155.573, 240.494) and CKD 1-2-3 vs. CKD 4-5 89.540 (95% CI 47.561, 131.518). Conclusions: In conclusion, our systematic review and meta-analysis highlights pronounced differences in UMD levels across multiple comparisons in CKD. When comparing CKD patients with controls, a significant decrease in UMD levels is evident, indicative of potential implications in renal pathology. Moreover, the observed variations in UMD levels between different CKD stages underscore its potential utility as a biomarker for disease severity and progression. These findings contribute to our understanding of UMD dynamics in CKD and suggest avenues for further research into its diagnostic and prognostic significance in clinical practice.

Update on the efficiency and safety of orally administered nasal decongestants

Nasal congestion leading to obstruction is one of the main symptoms in acute rhinosinusitis (common cold), other upper respiratory infections and allergic rhinitis. The EPOS 2020 guidelines place oral decongestants as an efficient therapy for the relief of nasal obstruction. In Romania, there are more than 50 available nasal decongestants, so it is very important for practitioners from all medical domains to be aware of recent data regarding their effectiveness and safety profile. Recent concerns raised by both the Food and Drug Administration (FDA) and the European Medicines Agency (EMA) regarding the efficacy and safety of pseudoephedrine (PSE) and phenylephrine (PHE) emphasize the need for informed decision-making in prescribing. Notably, there were concerns raised about the association between PSE, reversible cerebral vasoconstriction syndrome (RCVS) and posterior reversible encephalopathy syndrome (PRES). EMA’s safety committee, Pharmacovigilance Risk Assessment Committee (PRAC), recently recommended measures to minimize risks of serious side effects when using medicines containing PSE. PRAC recommends that medicines containing PSE should not be used in patients with severe or uncontrolled hypertension and severe acute or chronic kidney disease or failure. Additionally, PRAC recommends healthcare professionals to counsel patients to discontinue the use of such medicines promptly and seek medical assistance if they experience symptoms suggesting PRES or RCVS, such as sudden onset of severe headache, confusion, vomiting, visual disturbances or seizures. While effectiveness of oral PSE is confirmed by clinical studies, expert consensus is unfavorable to PHE. Both in vitro and in vivo clinical pharmacology data indicate that neither the recommended doses nor higher doses of oral PHE demonstrate efficacy in alleviating symptoms of nasal congestion.

Efficacy and safety of denosumab treatment for Korean patients with Stage 3b-4 chronic kidney disease and osteoporosis.

We evaluated the efficacy and safety of denosumab treatment in severe chronic kidney disease (CKD) patients with osteoporosis. We also investigated whether the treatment affects the coronary artery calcifications. Twenty-seven postmenopausal women with Stage 3b-4 CKD and osteoporosis were enrolled. Twenty patients received denosumab plus calcium carbonate and vitamin D, and seven controls received calcium carbonate and vitamin D for 1 year. Dual-energy X-ray absorptiometry and coronary artery calcium (CAC) scoring computed tomography were performed before and after treatment. Hypocalcemic symptoms and serum calcium levels were evaluated. After 1 year of treatment, the percent changes of femur neck (3.6 ± 3.2% vs. -0.7 ± 4.4%, p = 0.033) and total hip (3.4 ± 3.8% vs. -1.9 ± 2.1%, p = 0.001) bone mineral density (BMD) were significantly increased in the denosumab treated group compared to the control group. However, the percent change of lumbar spine BMD did not differ between two groups (5.6 ± 5.9% vs. 2.7 ± 3.9%, p = 0.273). The percent change of bone alkaline phosphatase was significantly different in the denosumab-treated group and control group (-31.1 ± 30.0% vs. 0.5 ± 32.0%, p = 0.027). CAC scores did not differ between groups. No hypocalcemic events occurred in both groups. If carefully monitored and supplemented with calcium and vitamin D, denosumab treatment for 1 year provides significant benefits in patients with Stage 3b-4 CKD and osteoporosis. However, denosumab treatment did not affect coronary artery calcifications in these patients.

Kidney function and other associated factors of sarcopenia in community-dwelling older adults: The SCOPE study

AimSarcopenia is associated with several factors and medical conditions among older adults, though previous research has shown limitations and inconsistencies, especially regarding chronic kidney disease (CKD). We investigated the clinical and laboratory variables associated with sarcopenia and severe sarcopenia in older adults, focusing on kidney function measures. MethodsData from community-dwelling adults aged ≥75 years participating in the SCOPE multicenter prospective cohort study were assessed cross-sectionally. Comprehensive geriatric assessment was conducted; sociodemographic and lifestyle factors, clinical variables and comorbidities, anthropometric and bioelectrical impedance analysis, blood and urine laboratory variables were collected. EWGSOP2 revised criteria were used to define sarcopenia and its severity. Estimated glomerular filtration rate (eGFR) was calculated using creatinine and non-creatinine-based equations, and CKD stages were defined accordingly. Results1420 participants were included, prevalence of sarcopenia was 10.6 %, and 6 % had severe sarcopenia. Multivariate logistic regression analysis showed that age [OR =1.14; 95 %CI (1.09–1.19)], body mass index (BMI) [0.83 (0.79–0.88)], disability performing instrumental activities of daily living (IADL) [2.61 (1.69–4.06)], Mini Mental State Examination (MMSE) score <24 [2.75 (1.62–4.67)], osteoporosis [2.39 (1.55–3.67)], and stage 4 CKD defined by CKD-EPIBTP-B2M, a non-creatinine-based eGFR equation [2.88 (1.11–7.49)], were independently associated with sarcopenia; as were specifically with severe sarcopenia, with more pronounced associations. ConclusionsIn community-dwelling older adults, sarcopenia is a relevant condition and is associated with severe CKD, older age, IADL, cognitive impairments, osteoporosis and low BMI. These factors should be assessed for proper identification and management of older patients with sarcopenia, and even more so with severe sarcopenia.

Feasibility of contrast-free left atrial appendage closure with WATCHMAN FLX device for patients with chronic kidney disease.

Contrast media are generally necessary for transcatheter left atrial appendage closure (LAAC), however, it should be avoided in patients with chronic kidney disease (CKD). The objective of this study was to evaluate the safety and feasibility of contrast-free LAAC with WATCHMAN FLX device for patients with CKD. Among 141 patients undergoing LAAC using the WATCHMAN FLX between May 2021 and March 2023, we performed LAAC without contrast media in 10 patients. Procedural and follow-up results were evaluated. The device size was selected based on the transesophageal echocardiographic (TEE) measurements. The device shape was assessed by fluoroscopy, and the device position was adjusted by TEE images. The mean age was 78 ± 4.9years, CHADS2 score was 3.2 ± 1.1, and the estimated glomerular filtration rate (eGFR) was 28 ± 12mL/min/1.73m2. The procedure was completed without contrast media in ten patients. Partial recapture of the device was required in four patients, but the initially selected device was finally implanted in all patients. Mean procedure time was significantly shorter in the contrast-free LAAC than in the contrast-use LAAC (41.6 ± 14.1min vs 30.3 ± 7.6min, p = 0.01). Postprocedural eGFR did not change from baseline, and there were no adverse events during the hospital stay. Follow-up TEE or cardiac computed tomography performed within 3months after the procedure revealed no device-related thrombus or peri-device leak > 3mm, and oral antithrombotic therapy was discontinued in all patients. Our experience shows that contrast-free LAAC using the WATCHMAN FLX device was safe and feasible. Non-contrast LAAC is one of the therapeutic options for patients with severe CKD.

Euvolemic automated transfusion to treat severe anemia in sickle cell disease patients at risk of circulatory overload.

Red blood cell (RBC) transfusion remains a major treatment for sickle cell disease (SCD). Patients with SCD have a high prevalence of renal impairment and cardiorespiratory disease, conferring risk of transfusion-associated circulatory overload (TACO). We describe an approach, titled euvolemic automated transfusion (EAT), to transfuse SCD patients with severe anemia who are at risk of TACO. In EAT, plasmapheresis is performed using donor RBCs, rather than albumin or plasma, as replacement fluid. Euvolemia is maintained. A retrospective analysis was conducted of patients with SCD who underwent EAT at our institution over a 10-year period, to evaluate the efficacy and safety of EAT. Eleven SCD patients underwent 109 EAT procedures (1-59 procedures per patient). The median age was 42 years (IQR = [30-49]) and 82% (n = 9) were female. Most (82%; n = 9) patients had severe chronic kidney disease and 55% (n = 6) had heart failure. One (9%) patient had a history of life-threatening TACO. Mean pre- and post-procedure Hct values were 19.8% (SD ± 1.6%) and 29.1% (SD ± 1.4%), respectively. The average Hct increment was 3.2% per RBC unit. Only two EAT-related complications were recorded during the 109 procedures: central line-associated infection and citrate toxicity (muscle cramping). EAT used an average of two RBC units less than that projected for standard automated RBC exchange. Our findings suggest that EAT is safe and effective to treat patients with SCD and severe anemia, who are at risk for TACO. EAT requires fewer RBC units compared to automated RBC exchange.

AD Biomarkers in Chronic Kidney Disease and Kidney Transplant

AbstractBackgroundBlood biomarkers of Alzheimer’s disease (AD) are elevated in chronic kidney disease (CKD). Whether this is due to deceased kidney clearance or increased production, and how they change with kidney transplant (KT), is unclear.MethodWe examined serum AD biomarkers from CKD patients pre‐ to post‐KT and compared findings with controls without CKD or AD. Analyses were performed on a Simoa HD‐X, using pTau181 and Neuro 4 Plex E assays.Age was used for covariate adjustment in linear mixed models (LMM) analyzing phosphorylated tau 181 (ptau181), neurofilament light (NfL), amyloid beta (AB42, AB40, 42/40), and glial fibrillary acidic protein (GFAP). Change in p‐tau181 was our primary outcome. LMM included age and levels for control, pre‐KT, or 12‐weeks or 1‐year post‐KT. Based on residual patterns, the natural log (In) of each measure was used for final analyses. Linear contrasts were used to generate estimated differences between group/time points from age‐adjusted models. These included averaged pre‐KT, post‐KT, and control comparisons. Two degree‐of‐freedom tests compared the post‐KT measures to pre‐KT and controls.ResultThe 59 CKD patients were 52±12 years old and 13 controls were 51±8 years old. Pre‐KT, ln(p‐tau181) was higher than controls (p&lt;0.0001) and post‐KT (p&lt;0.0001) (Figure). Post‐KT p‐tau181 greatly decreased but remained higher than controls (p = 0.0004). There was no difference between 12 weeks and 1 year post‐KT levels (p = 0.70). ln(pTau) increased with age (p = 0.06). ln(NfL) followed a similar pattern; pre‐KT levels were higher than controls (p&lt;0.0001) and post‐KT (p&lt;0.0001). Post‐KT levels decreased but remained higher than controls (p&lt;0.0001). 12‐week and 1‐year post‐KT levels did not differ (p = 0.57). Levels increased with age (p&lt;0.0001). Pre‐KT AB42 was higher than controls (p&lt;0.0001) and post‐KT (p&lt;0.0001). Post‐KT, levels decreased but remained higher than controls (p = 0.005) and continued declining 1‐year post‐transplant (p = 0.01). In(AB40) and In(GFAP) showed the same pattern. The AB42/AB40 was not different pre‐KT vs controls (p = 0.58) and did not change following KT. Cognitive function improved post‐KT. Patients with residual kidney function had lower baseline levels of AD blood biomarkers.ConclusionIn severe CKD, blood biomarkers of AD are dependent on kidney function and caution should be used in interpreting them.

Chronic kidney disease and risk of kidney or urothelial malignancy: systematic review and meta-analysis.

Chronic kidney disease (CKD) is highly prevalent, affecting approximately 11% of US adults. Multiple studies have evaluated a potential association between CKD and urinary tract malignancies. Summary estimates of urinary tract malignancy risk in CKD patients with and without common co-existing conditions may guide clinical practice recommendations. Four electronic databases were searched for original cohort studies evaluating the association between CKD and urinary tract cancers (kidney cancer and urothelial carcinoma) through 25 May 2023, in persons with at least moderate CKD and no dialysis or kidney transplantation. Quality assessment was performed for studies meeting inclusion criteria using the Newcastle-Ottawa Scale. Meta-analysis with a random-effects model was performed for unadjusted incidence rate ratios (IRR) as well as adjusted hazard ratios (aHR) for confounding conditions (diabetes, hypertension and/or tobacco use), shown to have association with kidney cancer and urothelial carcinoma. Sub-analysis was conducted for estimates associated with CKD stages separately. Six cohort studies with 8617563 persons were included. Overall, the methodological quality of the studies was good. CKD was associated with both higher unadjusted incidence and adjusted hazard of kidney cancer (IRR 3.36, 95% confidence interval (CI) 2.32-4.88; aHR 2.04, 95% CI 1.77-2.36) and urothelial cancer (IRR 3.96, 95% CI 2.44-6.40; aHR 1.35, 95% CI 1.22-1.50) compared with persons without CKD. Examining incident urinary tract cancers by CKD severity, risks were elevated in stage 3 CKD (kidney aHR 1.89, 95% CI 1.56-2.30; urothelial carcinoma aHR 1.35, 95% CI 1.20-1.52) as well as in stages 4/5 CKD (kidney cancer aHR 2.30, 95% CI 2.00-2.66; urothelial carcinoma aHR 1.24, 95% CI 1.04-1.49). Even moderate CKD is associated with elevated risk of kidney cancer and urothelial carcinoma. Providers should consider these elevated risks when managing individuals with CKD, particularly when considering evaluation for the presence and etiology of hematuria.

Prospective Identification of Variables As Outcomes for Treatment (PIVOT): A Phase II Clinical Trial of Hydroxyurea for Children and Adults with HbSC Disease

Introduction: HbSC is a common form of sickle cell disease especially prevalent in West Africa. Despite experiencing similar clinical events as those with sickle cell anemia (HbSS or HbSβ 0 thalassemia), individuals with HbSC disease have received much less attention because disease complications occur less frequently and often manifest later in life. Retrospective reports suggest that hydroxyurea might benefit people living with HbSC disease, but rigorous prospective data are unavailable to describe potential treatment benefits, long-term safety, and appropriate study endpoints. We designed a Phase II clinical trial of hydroxyurea for children and adults with HbSC disease with the following aims: 1) to measure possible laboratory toxicities of hydroxyurea; 2) to assess the clinical effects of hydroxyurea on sickle-related clinical and laboratory parameters; and 3) to identify study endpoints that are suitable for a future definitive Phase III trial of hydroxyurea for HbSC disease. Methods: Prospective Identification of Variables as Outcomes for Treatment (PIVOT, Trial ID PACTR202108893981080) is a double-blind, randomized, placebo-controlled Phase II trial of hydroxyurea. Inclusion criteria included people with HbSC disease, age 5 to 50 years, receiving care at Korle Bu Teaching Hospital, Accra, Ghana. Exclusion criteria included treatment with hydroxyurea or other disease-modifying treatment or participation in a therapeutic trial in the previous 6 months, hospitalization &amp;gt;10 times in the past 12 months, pregnancy, severe chronic kidney disease or other underlying illness making participation ill-advised, previous myelosuppressive therapy or stem cell transplant, or inability to take hydroxyurea. After written informed consent, participants underwent initial screening for 2 months before randomization to placebo or hydroxyurea (donated by Addmedica, Inc, Paris) with a goal of treating ~100 participants in each arm for one year. Randomization is stratified by age and sex to ensure equal numbers of children and adults with balanced baseline characteristics in each arm. The primary study outcome is cumulative hematological toxicities after 12 months of treatment. Here we report the baseline characteristics of the enrolled cohort. Results: From April 2022 to June 2023, a total of 243 patients with HbSC disease (123 children, 120 adults) consented and began screening (Figure); after ~10% screen failures, 217 (112 children, 105 adults) were eligible for randomization. The average age (mean ± SD) at enrollment was 21.9 ± 14.6 years and 47% were female. Baseline medical history documented that almost all study participants (93%) reported previous hospitalization, while 87% had previous vaso-occlusive events, 78% had malaria, 21% reported transfusion, and 1 patient had a stroke. Baseline labs included hemoglobin = 11.0 ± 1.3 g/dL, HbF = 1.8 ± 1.5 %, ANC = 3.7 ± 1.8 x 10 9/L, and platelets 269 ± 115 x 10 9/L. Additional baseline laboratory studies include whole blood viscosity, ektacytometry, and point-of-sickling. Baseline assessment revealed a palpable spleen in 6 children (5%) and 1 adult (1%), but abdominal ultrasonography documented splenic tissue in 97% of children and 83% of adults with an average volume of 116 ± 71 mL (range 13 - 354 mL) and 222 ± 165 mL (range 4 - 707 mL), respectively. TCD examinations on children revealed an average maximum time-averaged mean velocity of 111 ± 19 cm/sec with 98% normal exams, 1% conditional, 0% abnormal, and 1% inadequate. Retinopathy was identified in 46% of children and 85% of adults, including both proliferative and non-proliferative findings. Near Infrared Spectrometry (NIRS), 6-minute walk, and Quality of Life were also collected. Discussion: Individuals with HbSC endure a substantial number of life-altering clinical complications and early mortality. Better treatments for this large group of people are desperately needed, and hydroxyurea is an obvious choice due to its low cost and ease of oral administration. Better understanding of the rate and severity of disease manifestations across the age span is needed to more completely understand the best time to treat this group to mitigate complications. Now fully enrolled, PIVOT will provide invaluable insights into the effects and potential benefits of hydroxyurea on clinical and laboratory outcomes among people living with HbSC disease.

Tolerability and Outcomes of Bruton Tyrosine Kinase Inhibitors for Chronic Lymphocytic Leukemia in Patients with Severe Renal Dysfunction

Introduction: There is limited data on the outcomes and tolerability of Bruton Tyrosine Kinase (BTK) inhibitors for chronic lymphocytic leukemia (CLL) in patients with severe renal dysfunction, particularly older adults. The most commonly prescribed BTK inhibitor, ibrutinib, is believed to be safe for mild to moderate renal dysfunction. However, severe renal failure has been excluded from prospective studies, and there is no guidance on dosing under the FDA label. Furthermore, ibrutinib itself can cause kidney injury and worsen existing renal dysfunction. This national Veterans Affairs (VA) analysis aims to review the safety and tolerability of BTK inhibitors in severe renal impairment. Methods: An electronic query of the VA Corporate Data Warehouse and retrospective chart review were performed to identify patients with CLL treated with a BTK inhibitor between 2013-2022 and who had severe chronic kidney disease defined as an estimated glomerular filtration rate (eGFR) &amp;lt; 30 ml/min/1.73 m 2 overlapping with their treatment period. Isolated acute kidney injuries lasting &amp;lt; 1 month were excluded. Fisher's exact test was utilized to evaluate categorical variables, logistic regression for binary outcomes, and log-rank and Cox regression for time-to-event analyses. Results: A total of 115 patients across 68 VA medical centers received 124 lines of BTK inhibitors with an eGFR &amp;lt; 30 (Table 1). The median duration of follow-up from the start of therapy was 26 months (range, 0.5 - 94). The median age was 74, and 98% were male, reflecting the U.S. veteran population. 64% had an eGFR &amp;lt; 30 at the start of therapy, with 18% requiring dialysis, while the remaining 36% experienced progressive renal dysfunction during treatment. The oral BTK agents prescribed were ibrutinib ( n = 103), acalabrutinib ( n = 18), and zanubrutinib ( n = 3). Most BTK inhibitors (n = 94 of 124 lines, 76%) were initiated at the FDA-label dose. 46 (37%) later required dose reduction, primarily due to drug toxicity ( n = 37). The most common reasons for dose reduction were cytopenia ( n = 10), failure to thrive ( n = 6), bleeding ( n = 5), and worsening renal function ( n = 5). Discontinuation of therapy for toxicity occurred in 50% (ibrutinib), 39% (acalabrutinib), and 33% (zanubrutinib). The most common reasons for discontinuation were infection ( n = 15), bleeding ( n = 10), arrhythmia ( n = 9), and disease progression ( n = 9). Among patients who received ibrutinib ( n = 103), the median progression-free survival (PFS) and overall survival (OS) were 45 and 49 months, respectively. In multivariate Cox regression, covariates associated with shorter PFS included the baseline severity of renal failure (HR 1.85, 95% CI 1.21 - 2.88), cirrhosis (HR 6.36, 95% CI 1.45 - 19.76), and heart failure (HR 4.20, 95% CI 1.82 - 9.47). Younger age, dialysis, and absence of atrial fibrillation at the start of therapy were protective in univariate but not multivariate models. Heart failure and cirrhosis retained their prognostic impact on OS in multivariate modeling. Factors including race, rural residence, obesity, IGHV status, and TP53 deletion were not significantly associated with survival in this cohort. The median duration of therapy of ibrutinib was 33 months. Ibrutinib dose reductions at initiation or during treatment were associated with a longer duration of therapy (Figure 1). Of note, dose reductions did not significantly reduce the response rate to ibrutinib or worsen survival. Interestingly, 11 patients had CLL-related kidney dysfunction. However, kidney function did not improve after treatment with a BTK inhibitor in any of the 115 patients. Progression of renal impairment was observed in 51 patients (50%) on ibrutinib, 8 (44%) on acalabrutinib, and none on zanubrutinib. The etiology of worsening renal function was uncertain for the majority of patients. Conclusion: The clinical outcomes of BTK inhibitors in patients with CLL and severe renal dysfunction have not been well-described. In our real-world data analysis, these agents appear to be a reasonable therapeutic option in severe renal impairment, including in older adults and those on dialysis. Lab monitoring is needed, given the risk of worsening renal function. Dose modifications may help improve tolerability without reducing efficacy. Unfortunately, severe renal dysfunction is unlikely to improve with CLL treatment, even in CLL-related kidney failure.

Chronic kidney disease and functional impairment in a longitudinal study of older adults in China

ObjectivesTo examine the associations of chronic kidney disease (CKD) with dynamic functional impairment among older Chinese adults.DesignThis was a prospective longitudinal study.SettingData were derived from the Chinese Longitudinal Healthy Longevity...

Patient-Reported Outcomes Measures, Polycystic Kidney Disease Burden, and Outcomes in Autosomal Dominant Polycystic Kidney Disease

Rationale & ObjectiveUsing OVERTURE (NCT01430494) study data on patient-perceived health, healthcare utilization, and productivity in autosomal dominant polycystic kidney disease (ADPKD), this research was conducted to characterize the burden of illness in ADPKD patients and assess whether patient-reported outcomes (PRO) assessment scores predict clinical and health-economic outcomes. Study DesignAnalyses of data from a prospective, observational study. Setting & ParticipantsThe study cohort comprised 3409 individuals with ADPKD in 20 countries, ages 12–78 years, in chronic kidney disease (CKD) stages G1–G5 and Mayo risk subclasses 1A–1E. PredictorsScores on PRO instruments, including disease-specific assessments (ADPKD-Impact Scale [ADPKD-IS], ADPKD-Urinary Impact Scale [ADPKD-UIS]) and generic measures. OutcomesClinical variables (e.g., height-adjusted total kidney volume [htTKV], estimated glomerular filtration rate [eGFR], abdominal girth) and health-economic outcomes. Analytical ApproachAssociations among variables were evaluated using Spearman correlations, logistic regression, and generalized linear mixed-effects repeated-measures models. ResultsBaseline CKD stage and Mayo risk classification showed little correlation with baseline PRO scores, although scores on disease-specific instruments and measures of physical functioning were worse at more severe CKD stages. PRO scores predicted hospitalizations and sick days at 6–18 months, with associations strongest for the ADPKD-IS. Whereas PRO scores were not associated with htTKV and eGFR, worse PRO scores were associated with greater abdominal girth. Poor baseline ADPKD-IS scores were positively associated with occurrence of ADPKD-related symptoms up to 18 months, including kidney pain (odds ratio [OR] 5.30, 95% confidence interval [CI] 2.75–10.24), hematuria (OR 4.58, 95% CI 1.99–10.53), and urinary tract infection (OR 4.41, 95% CI 1.93–10.11; P<0.001 for all). LimitationsMaximum 18 months of follow-up to assess outcomes. ConclusionsPRO scores predicted clinical and health-economic outcomes such as hospitalization and absence from work, underscoring the importance of quality of life assessment of individuals with ADPKD.

Real world prognostic impact and predictors of adherence to statin therapy after STEMI on first year follow up: results from the FAST STEMI registry

Abstract Background The impact of statin therapy on cardiovascular outcomes after ST-elevation acute myocardial infarction (STEMI) in real-world patients is understudied. Purpose The aim of this study was to identify predictors of low compliance to statin therapy and estimate its impact on cardiovascular (CV) outcomes and mortality in the first year after the index event. Methods We evaluated real-world adherence to the most common cardiovascular drugs by comparing the number of bought tablets in drugstores to the expected tablets at 1 year and on total follow-up length. A total amount of 6043 patients from 2012 to 2017 was enrolled in the FAST STEMI registry and followed up for 4,7±1,6 years; 299 patients with intraprocedural and intrahospital deaths were excluded. The main outcomes evaluated were all-cause death, cardiovascular death, myocardial infarction, major and minor bleeding events and ischemic stroke. The best compliance cut-off was found by ROC curve analysis with Youden index; Kaplan Meier and Cox proportional hazard models were performed to evaluate cumulative event rates of cardiovascular mortality at follow-up. Predictors of lower adherence were evaluated at univariate and multivariate analysis with logistic regression. Results From a total of 5744 patients 4333 were men (75,4%) with an average age of 64,7±12,5 years old; 699 (2,2%) were diabetic, 311 (5,4%) presented with severe chronic kidney disease (CKD) while 237 (4,1%) had previous ischemic cardiopathy disease. Mean statin adherence was 89,9% (IQR 41,1 – 100): after univariate and multivariate analysis age≥75 (OR 0.597, IC 0.514-0.692), previous ischemic stroke (OR 0.607, IC 0.416-0.886), known ischemic cardiopathy (OR 0.675, IC 0.503-0.904) and chronic kidney disease (OR 0.667, IC 0.552-0.879) resulted as predictors of lower compliance, whereas preserved ejection fraction (OR 1.282, IC 1.133-1.457) resulted predictor of adequate adherence to statin therapy. Statin adherence upper than 49.05% (identified at Youden’s analysis as best cut-off) reduced both cardiovascular (0,3% vs. 6,8%; HR 0.33; 95%CI 0.18-0.59; p = 0,001) and all-cause mortality (0,7% vs 18,1%, HR 0,22, 95%CI 0.15-0.37, p&amp;lt;0.001). Regarding cardiovascular outcomes, statin optimal adherence reduced ischemic stroke incidence (1% vs 2,5%, p=0.001) while there was no difference on the number of myocardial infarctions nor hemorrhagic events at 1-year follow up. Conclusions In the real-world setting, statin adherence after STEMI was independently associated to a reduction of cardiovascular mortality, all-cause mortality and ischemic stroke incidence at 1-year follow-up. Elderly age, previous ischemic stroke, known ischemic cardiopathy and CKD resulted as independent predictors of lower compliance to statin therapy.CV and all-cause mortalityCox regression on CV mortality at 1-year

Ticagrelor versus Clopidogrel in diabetes patients afflicted with acute coronary syndrome stratified by renal function

Abstract Background Ticagrelor has been recommended in place of clopidogrel as part of dual antiplatelet therapy (DAPT) in diabetic patients with acute coronary syndrome (ACS). Chronic kidney disease (CKD) patients also have a worse prognosis in the setting of ACS, but the safety and efficacy data for the use of P2Y12 inhibitors in moderate to severe CKD patients (eGFR &amp;lt;60 mL/min/1.73m2) are insufficient. Purpose There has been limited data on the outcome of prescribing ticagrelor compared to clopidogrel in ACS-DM patients with chronic kidney disease (CKD). Methods This prospective, nationwide, multi-center, observational study, the Acute Coronary Syndrome-Diabetes Mellitus Registry (ACS-DM Registry) was compiled from consecutive patients between October 1, 2013 and September 30, 2016. The primary end point was repeated revascularisation and the composite outcome was CV death, repeat revascularisation and CV-related readmission, was stratified by renal function stages. The Cox proportional hazards models and propensity score models were applied to six-months, one-year, and two-year post ACS, respectively. Results There were 539 patients with moderate to severe CKD or on dialysis identified from ACS-DM Registry. There were 451 patients eligible for inclusion criteria of which 116 patients were taking ticagrelor and 335 patients were taking clopidogrel. At our two-year follow-up, the unadjusted incidence of primary end point resulted higher in Ticagrelor group (HR 2.09, 95% CI 1.37-3.18, p = 0.001). After adjustment, ticagrelor also had poor primary end point event and composite outcome as compared to clopidogrel (HR 2.24, 95% CI 1.36-3.68, p = 0.002; HR 1.63, 95% CI 1.06-2.48, p = 0.024, respectively). In regards to the repeated revascularisation issue, the clopidogrel was preferable within the eGFR strata (CKD stage III: HR 2.53, 95% CI 1.32-4.84, CKD stage IV: 1.06 (0.09-12.51), CKD stage V: 1.91 (0.80-4.59), P for interaction=0.684). Conclusions Cardiovascular benefits associated with ticagrelor may not be as significant as in the landmark trial. Our results show that patients taking ticagrelor was associated with increased CV events as compared to clopidogrel in ACS-DM patients with stage III-V CKD.propensity score matchingForest plots