Social Isolation Is Associated With Rapid Kidney Function Decline and the Development of Chronic Kidney Diseases in Middle-Aged and Elderly Adults: Findings From the China Health and Retirement Longitudinal Study (CHARLS)

Background: There is limited evidence on the relationship between social isolation and renal outcomes. To address this gap, this study estimated the prospective relationship of social isolation with rapid kidney function decline and the development of chronic kidney disease (CKD) in middle-aged and elderly Chinese with normal kidney function.Methods: We analyzed data from 3,031 participants aged ≥ 45 years with baseline estimated glomerular filtration rates (eGFR) ≥ 60 ml/min/1.73 m2. All data were obtained from the 2011 and 2015 waves of the Chinese Longitudinal Study of Health and Retirement (CHARLS). eGFR was estimated based on a combination of serum creatinine and cystatin C. The primary outcome was rapid decline in renal function, as defined by an eGFR decrease of > 5 ml/min/1.73 m2 per year, while the secondary outcome was the development of CKD, as defined by an eGFR decrease to a level < 60 ml/min/1.73 m2.Results: During the follow-up of 4 years, 258 (8.5%) participants experienced a rapid decline in renal function, while 87 (2.9%) developed CKD. In the fully adjusted model, high social isolation was significantly related to an increased risk of experiencing a rapid decline in renal function (OR 1.805, 95% CI 1.310–2.487) and CKD onset (OR 1.842, 95% CI 1.084–3.129). Among the five components of social isolation, being unmarried, not participating in social activities, and living alone independently predicted declined renal function.Conclusions: Social isolation is significantly associated with the risk of rapid eGFR decline and CKD onset in middle-aged and older adults with normal kidney function in China.

Osteoporosis after heart transplantation with reference to immunosuppression and renal function

Background Osteoporosis is commonly found in heart transplantation (HT) recipients, and may develop as an adverse effect of the immunosuppressive therapy, as well as be a consequence of factors associated with heart failure prior to HT. Chronic kidney disease (CKD) is furthermore, like osteoporosis, frequently found in the HT patient population, and may also arise as a side-effect of the immunosuppressive therapy. Aims and method We sought to describe the bone mineral density (BMD) evolution, predictors of osteoporosis, and survival, as well as incidence of osteoporosis in relation to CKD up to 10 years after HT. The project was conducted as a retrospective cohort study including patients who underwent HT at an age of at least 20 years between January 1988 and June 2016 at our center. The project was approved by the local ethics board (approval nos. 2010/114, 2011/777, 2014/92). Results Pre-transplant BMD was a negative predictor of osteoporosis during the first post-operative year, with a HR of 0.13 (95% CI 0.063; 0.26; P<0.001) and 0.54 (95% CI 0.34; 0.85; P<0.001) in the lumbar spine and femoral neck, respectively, adjusted for age, gender, BMI, and immunosuppressive therapy. Similarly, pre-transplant BMD was a negative predictor of osteoporosis also up to 10 years after HT, with a HR of 0.19 (95% CI 0.11; 0.32; P<0.001) and 0.55 (95% CI 0.39; 0.78; P=0.001), in the lumbar spine and femoral neck, respectively, adjusted for age, gender, BMI, and immunosuppressive therapy. CKD stage 3 or worse before HT was associated with a greater gain in BMD after HT compared with CKD stage less than 3 or normal kidney function (−2.5% [−5.6; 0.6] versus −6.6% [−8.8;-4.5], P=0.029), and was not associated with osteoporosis (Figure 1). Also, the cumulative incidence of osteoporosis in the lumbar spine after HT was higher in the group with CKD stage less than 3 or normal kidney function. Conclusions The greatest drop in BMD occurs within the first year after HT. Short- and long-term incidence of osteoporosis is positively associated with pre-transplant bone strength, suggesting that early initiation of osteoporosis preventive treatment, pharmacologically and non-pharmacologically, may be beneficial in preventing long- and short-term fracture-related morbidity and morbidity after HT. Moreover, CKD stage 3 or worse before HT was associated with higher lumbar BMD after HT, and was not a predictor of osteoporosis. CKD stage less than 3 or normal kidney function before HT exhibited a greater BMD loss in the lumbar spine. Finally, the change in GFR during the first postoperative year was not associated with long-term BMD loss or osteoporosis. FUNDunding Acknowledgement Type of funding sources: Foundation. Main funding source(s): Anna-Lisa & Sven-Erik Lundgren's Foundation and ALF's Foundations, Lund, Sweden Figure 1

Effect of Low-dose Methotrexate on Estimated Glomerular Filtration Rate and Kidney Adverse Events: A Randomized Clinical Trial

Background: Low-dose methotrexate (LD-MTX) is contraindicated in advanced chronic kidney disease (CKD), but the kidney safety in normal kidney function or mild-to-moderate CKD is less clear. Methods: We performed a secondary analysis for eGFR and kidney AEs using the randomized double-blind, placebo-controlled Cardiovascular Inflammation Reduction Trial. Adults with cardiovascular disease and diabetes and/or metabolic syndrome were randomly allocated to oral LD-MTX (target dose 15-20 mg/week) or placebo. All participants took folic acid 1 mg six days/week. Exclusion criteria included systemic rheumatic disease and creatinine clearance <40 mL/min. The least-squares mean ΔeGFR from baseline was calculated at each study visit; the difference in eGFR between LD-MTX and placebo was compared. We used Cox proportional hazards models to compare rates of kidney AEs for LD-MTX versus placebo. Results: A total of 2,391 participants were randomized to LD-MTX and 2,395 to placebo. At baseline, mean age was 66 years, 19% were female, and mean eGFR was 80.0mL/min/1.73m2 (54% had Stage 2 CKD and 18% had Stage 3 CKD). Median follow-up was 23 months. The LD-MTX group had less decline in eGFR than placebo (difference in least-squares mean ΔeGFR from baseline to on-treatment visits: 0.93mL/min/1.73m2, 95%CI 0.45-1.40, p<0.001). There were 138 (incidence rate [IR] 2.97 per 100 person-years) kidney AEs in the LD-MTX group and 184 (IR 3.99 per 100 person-years) among placebo (hazard ratio [HR] 0.73, 95%CI 0.59-0.91) during safety laboratory monitoring. Conclusions: These results demonstrate the kidney safety of LD-MTX among patients with normal kidney function or mild/moderate CKD at baseline.

Potency of propofol for inducing loss of consciousness in end-stage kidney disease patients

It can be difficult for anesthesiologists to determine the optimal dose of propofol for end-stage kidney disease (ESKD) patients due to changes in drug disposition. The purpose of this study was to evaluate the potency of propofol for inducing loss of consciousness in ESKD patients. Patients with normal kidney function (Control group, n = 15), those with ESKD (ESKD group, n = 15), and those with ESKD undergoing cervical epidural anesthesia (ESKD-CEB group, n = 15) were administered propofol by target-controlled infusion (TCI) using the Schneider model. The effect-site concentration (Ce) of propofol started at 0.5 μg/ml and increased in increments of 0.5 μg/ml until the patient did not respond to verbal commands. The relationship between the probability (P) of loss of consciousness and the Ce of propofol was analyzed in each group using logistic regression. The Ce values of propofol at the time of loss of consciousness were 4.3 ± 0.9, 3.7 ± 0.9, and 3.3 ± 1.0 μg/ml for the Control, ESKD, and ESKD-CEB* groups, respectively (*significant difference vs. control, P < 0.05). The estimated Ce50 values for lost ability to respond to verbal command were 4.56, 3.75, and 3.21 μg/ml for the Control, ESKD, and ESKD-CEB groups, respectively. In conclusion, when inducing anesthesia in ESKD patients, we recommend using an initial dose similar to that of patients with normal kidney function, or rather starting with a lower dose.

Differential Performance of Neutrophil Gelatinase-Associated Lipocalin and Cystatin C to Predict Ischemic Stroke

Objective Both cystatin C (CysC) and neutrophil gelatinase-associated lipocalin (NGAL) are markers of kidney injury and may also be marker candidates for neuroinflammation. The aim of this article is to explore the relationship between kidney injury and ischemic stroke (IS).Methods 498 IS patients were enrolled, and 173 IS-related disease control (DC) patients and 293 healthy control (HC) subjects were randomly selected. We analyzed the relationship between the levels of serum kidney function markers (including NGAL, Cre, Ure, CysC and eGFR) and the occurrence of IS.Results When they were admitted to the hospital, the NGAL level of patients with first-onset IS was higher than that of both HC group (z=5.964, P<0.001) and DC (z=12.191, P<0.001); The level of CysC of them was higher than that of HC group (z=5.762, P<0.001), and was the similar with that of DC group (z=1.663, P=0.289). The partial correlation coefficient between NGAL and the occurrence of IS was the highest (rp=0.341, P<0.001) in IS patients with normal kidney function. However, the partial correlation coefficient between CysC and IS was the highest (rp=0.460) , P<0.001) in IS patients with chronic kidney disease (CKD). For patients with normal kidney function, only NGAL was a risk factor for IS [OR(95%CI)=6.54(3.75,11.41)], and had the certain predictive performance AUC=0.734(z=12.928, P<0.001). However, for CKD patients, CysC has better predictive performance for IS occurrence AUC=0.835 (z=11.343, P<0.001) and risk assessment ability [OR(95%CI)=5.97(2.45, 14.56)] than NGAL.Conclusion IS is related to kidney injury and neuroinflammation. NGAL and CysC are suitable for IS prediction in patients with normal kidney function and CKD, respectively. Researchers should pay attention to the changes of NGAL and CysC for the prevention and treatment of stroke in these two types of patients, respectively.

Association of Depressive Symptoms with Rapid Kidney Function Decline in Adults with Normal Kidney Function

Background and objectivesThe relationship of depressive symptoms with kidney function remains poorly investigated. We aimed to evaluate the prospective association between depressive symptoms and rapid decline in kidney function in Chinese adults with normal kidney function.Design, setting, participants, & measurementsA total of 4763 participants with eGFR≥60 ml/min per 1.73 m2 at baseline were enrolled from the China Health and Retirement Longitudinal Study. Baseline depressive symptoms were determined using a ten-item Center for Epidemiologic Studies Depression scale with a cutoff score of greater than or equal to ten to define high depressive symptoms. The GFR was estimated by a combination of serum creatinine and cystatin C. The primary outcome was rapid decline in kidney function, defined as an annualized decline in eGFR of ≥5 ml/min per 1.73 m2. Secondary outcome was defined as an annualized decline in eGFR of ≥5 ml/min per 1.73 m2 and to a level of <60 ml/min per 1.73 m2 at the exit visit.ResultsDuring a median follow-up of 4 years (interquartile range, 3.92–4.00), 260 (6%) participants developed rapid decline in kidney function. Overall, there was a significant positive association between baseline depressive symptoms and rapid decline in kidney function (per five-scores increment; adjusted odds ratio, 1.15; 95% confidence interval, 1.03 to 1.28) after adjustments for major demographic, clinical, or psychosocial covariates. Consistently, compared with participants with low depressive symptoms (total Center for Epidemiologic Studies Depression scale score less than ten), a significantly higher risk of rapid decline in kidney function was found among those with high depressive symptoms (total Center for Epidemiologic Studies Depression scale score greater than or equal to ten; adjusted odds ratio, 1.39; 95% confidence interval, 1.03 to 1.88). Similar results were found for the secondary outcome (per five-scores increment; adjusted odds ratio, 1.26; 95% confidence interval, 1.06 to 1.51).ConclusionsHigh depressive symptoms were significantly associated with a higher risk of rapid kidney function decline among Chinese adults with normal kidney function.

Does chronic kidney disease affect implant survival after primary hip and knee arthroplasty?

Aims To investigate whether chronic kidney disease (CKD) is associated with the risk of all-cause revision or revision due to a periprosthetic joint infection (PJI) after primary hip or knee arthroplasty. Methods This retrospective cohort study comprised 18,979 consecutive hip and knee arthroplasties from a single high-volume academic hospital. At a median of 5.6 years (interquartile range (IQR) 3.5 to 8.1), all deaths and revisions were counted. To overcome the competing risk of death, competing risk analysis using the cumulative incidence function (CIF) was applied to analyze the association between different stages of CKD and revisions. Confounding factors such as diabetes and BMI were considered using either a stratified CIF or the Fine and Gray model. Results There were 2,111 deaths (11.1%) and 677 revisions (3.6%) during the follow-up period. PJI was the reason for revision in 162 cases (0.9%). For hip arthroplasty, 3.5% of patients with CKD stage 1 (i.e. normal kidney function, NKF), 3.8% with CKD stage 2, 4.2% with CKD stage 3, and 0% with CKD stage 4 to 5 had undergone revision within eight years. For knee arthroplasty, 4.7% with NKF, 2.7% with CKD stage 2, 2.4% with CKD stage 3, and 7% of CKD stage 4 to 5 had had undergone revision. With the exception of knee arthroplasty patients in whom normal kidney function was associated with a greater probability of all-cause revision, there were no major differences in the rates of all-cause revisions or revisions due to PJIs between different CKD stages. The results remained unchanged when diabetes and BMI were considered. Conclusion We found no strong evidence that CKD was associated with an increased risk of all-cause or PJI-related revision. Selection bias probably explains the increased amount of all-cause revision operations in knee arthroplasty patients with normal kidney function. The effect of stage 4 to 5 CKD was difficult to evaluate because of the small number of patients. Cite this article: Bone Joint J 2021;103-B(4):689–695.