Quantitative assessment of lumbar spine bone marrow in patients with different severity of CKD by IDEAL-IQ magnetic resonance sequence.

Background: Chronic kidney disease (CKD) has a significant negative impact on bone health. Bone marrow is an essential component of bone, mainly composed of trabecular bone and fat. The IDEAL-IQ sequence of MRI allows indirect quantification of trabecular bone mass by R2* and direct quantification of bone marrow fat content by FF map, respectively. Objective: Our objective was to explore the association of CKD severity with bone marrow using IDEAL-IQ and whether mineral and bone metabolism markers alter this association. Method: We recruited 68 CKD patients in this cross-sectional research (15 with CKD stages 3-4, 26 with stage 5, and 27 with stage 5d). All patients underwent lumbar spine IDEAL-IQ, BMD, and several bone metabolism markers (iPTH, 25-(OH)-VitD, calcium and phosphorus). Multiple linear regression analysis was used to examine the association of CKD severity with MRI measurements (R2* and FF). Results: More severe CKD was associated with a higher R2* value [CKD 5d versus 3-4: 30.077 s-1 (95% CI: 12.937, 47.217), P for trend < 0.001], and this association was attenuated when iPTH was introduced [CKD 5d versus 3-4: 19.660 s-1 (95% CI: 0.205, 39.114), P for trend = 0.042]. Furthermore, iPTH had an association with R2* value [iPTH (pg/mL): 0.033 s-1 (95% CI: 0.001, 0.064), P = 0.041]. Besides, FF was mainly affected by age and BMI, but not CKD. Conclusions: The bone marrow R2* value measured by IDEAL-IQ sequence is associated with CKD severity and iPTH. The R2* of IDEAL-IQ has the potential to reflect lumbar bone changes in patients with CKD.

Acute Kidney Injury After CT in Emergency Patients with Chronic Kidney Disease: A Propensity Score-matched Analysis.

INTRODUCTION: Acute kidney injury (AKI) after intravenous contrast administration for computed tomography (CT) occurs infrequently, but certain patients may be susceptible. This study evaluated AKI incidence among emergency department (ED) patients with pre-existing chronic kidney disease (CKD) undergoing CT exams. METHODS: This retrospective cohort study in an integrated healthcare system included ED patients previously diagnosed with CKD stages 3-5 (estimated glomerular filtration rate <60 milliliters per minute per 1.73 meters squared over at least three months), undergoing CT exams with or without intravenous contrast, from January 1, 2013-December 31, 2017. We excluded patients with CT prior to (30 days) or following (14 days) index CT and missing serum creatinine (sCr) measurements. We applied propensity score matching, and then multivariable regression adjustment for post-CT ED disposition and ED diagnosis, to calculate adjusted risk of AKI. Secondary patient-centered outcomes included 30-day mortality, end-stage renal disease (ESRD) diagnosis, and dialysis initiation. RESULTS: Among 103,573 eligible ED patients undergoing CT, propensity score matching yielded 5,589 pairs. Adjusted risk ratio (ARR) for AKI was higher overall for contrast-enhanced CT (1.60; 95% confidence interval [CI], 1.43-1.79). However, secondary outcomes were infrequent: 19/5,589 non-contrast vs 40/5,589 contrast patients with new dialysis initiation at 30 days (adjusted risk 0.3% vs 0.7%; adjusted risk reduction 0.4%; 95% CI, 0.1%-0.7%). CONCLUSION: In ED patients with chronic kidney disease undergoing CT, intravenous contrast was associated with higher overall adjusted risk of AKI, but patient-centered secondary outcomes were rare. The clinical significance of transient kidney injury after CT is unclear, although patients with advanced chronic kidney disease appear to have elevated risk.

Effects of chronic kidney disease and declining renal function on coronary atherosclerotic plaque progression: a PARADIGM substudy.

AIMS: To investigate the change in atherosclerotic plaque volume in patients with chronic kidney disease (CKD) and declining renal function, using coronary computed tomography angiography (CCTA). METHODS AND RESULTS: In total, 891 participants with analysable serial CCTA and available glomerular filtration rate (GFR, derived using Cockcroft-Gault formulae) at baseline (CCTA 1) and follow-up (CCTA 2) were included. CKD was defined as GFR <60 mL/min/1.73 m2. Declining renal function was defined as ≥10% drop in GFR from the baseline. Quantitative assessment of plaque volume and composition were performed on both scans. There were 203 participants with CKD and 688 without CKD. CKD was associated with higher baseline total plaque volume, but similar plaque progression, measured by crude (57.5 ± 3.4 vs. 65.9 ± 7.7 mm3/year, P = 0.28) or annualized (17.3 ± 1.0 vs. 19.9 ± 2.0 mm3/year, P = 0.25) change in total plaque volume. There were 709 participants with stable GFR and 182 with declining GFR. Declining renal function was independently associated with plaque progression, with higher crude (54.1 ± 3.2 vs. 80.2 ± 9.0 mm3/year, P < 0.01) or annualized (16.4 ± 0.9 vs. 23.9 ± 2.6 mm3/year, P < 0.01) increase in total plaque volume. In CKD, plaque progression was driven by calcified plaques whereas in patients with declining renal function, it was driven by non-calcified plaques. CONCLUSION: Decline in renal function was associated with more rapid plaque progression, whereas the presence of CKD was not.

Osteoporosis in Patients with Chronic Kidney Diseases: A Systemic Review.

Chronic kidney disease (CKD) is associated with the development of mineral bone disorder (MBD), osteoporosis, and fragility fractures. Among CKD patients, adynamic bone disease or low bone turnover is the most common type of renal osteodystrophy. The consequences of CKD-MBD include increased fracture risk, greater morbidity, and mortality. Thus, the goal is to prevent the occurrences of fractures by means of alleviating CKD-induced MBD and treating subsequent osteoporosis. Changes in mineral and humoral metabolism as well as bone structure develop early in the course of CKD. CKD-MBD includes abnormalities of calcium, phosphorus, PTH, and/or vitamin D; abnormalities in bone turnover, mineralization, volume, linear growth, or strength; and/or vascular or other soft tissue calcification. In patients with CKD-MBD, using either DXA or FRAX to screen fracture risk should be considered. Biomarkers such as bALP and iPTH may assist to assess bone turnover. Before initiating an antiresorptive or anabolic agent to treat osteoporosis in CKD patients, lifestyle modifications, such as exercise, calcium, and vitamin D supplementation, smoking cessation, and avoidance of excessive alcohol intake are important. Managing hyperphosphatemia and SHPT are also crucial. Understanding the complex pathogenesis of CKD-MBD is crucial in improving one's short- and long-term outcomes. Treatment strategies for CKD-associated osteoporosis should be patient-centered to determine the type of renal osteodystrophy. This review focuses on the mechanism, evaluation and management of patients with CKD-MBD. However, further studies are needed to explore more details regarding the underlying pathophysiology and to assess the safety and efficacy of agents for treating CKD-MBD.

Site-specific chelation therapy with EDTA-loaded albumin nanoparticles reverses arterial calcification in a rat model of chronic kidney disease.

Medial arterial calcification (MAC) is a common outcome in diabetes and chronic kidney disease (CKD). It occurs as linear mineral deposits along the degraded elastin lamellae and is responsible for increased aortic stiffness and subsequent cardiovascular events. Current treatments for calcification, particularly in CKD, are predominantly focused on regulating the mineral disturbance and other risk factors. Ethylene diamine tetraacetic acid (EDTA), a chelating agent, can resorb mineral deposits, but the systemic delivery of EDTA may cause side effects such as hypocalcemia and bone resorption. We have developed elastin antibody conjugated albumin nanoparticles that target only degraded elastin in vasculature while sparing healthy tissues. In this study, we tested a targeted nanoparticle-based EDTA chelation therapy to reverse CKD-associated MAC. Renal failure was induced in Sprague-Dawley rats by a high adenine diet supplemented by high P and Ca for 28 days that led to MAC. Intravenous delivery of DiR dye-loaded nanoparticles confirmed targeting to vascular degraded elastin and calcification sites within 24 hours. Next, EDTA-loaded albumin nanoparticles conjugated with an anti-elastin antibody were intravenously injected twice a week for two weeks. The targeted nanoparticles delivered EDTA at the site of vascular calcification and reversed mineral deposits without any untoward effects. Systemic EDTA injections or blank nanoparticles were ineffective in reversing MAC. Reversal of calcification seems to be stable as it did not return after the treatment was stopped for an additional four weeks. Targeted EDTA chelation therapy successfully reversed calcification in this adenine rat model of CKD. We consider that targeted NP therapy will provide an attractive option to reverse calcification and has a high potential for clinical translation.

Vitamin D supplementation enhances the fixation of titanium implants in chronic kidney disease mice.

Vitamin D (Vit D) deficiency is a common condition in chronic kidney disease (CKD) patients that negatively affects bone regeneration and fracture healing. Previous study has shown that timely healing of titanium implants is impaired in CKD. This study aimed to investigate the effect of Vit D supplementation on implant osseointegration in CKD mice. Uremia was induced by 5/6 nephrectomy in C57BL mice. Eight weeks after the second renal surgery, animals were given 1,25(OH)2D3 three times a week intraperitoneally for four weeks. Experimental titanium implants were inserted into the distal end of femurs two weeks later. Serum measurements confirmed decreased 1,25(OH)2D levels in CKD mice, which could be successfully corrected by Vit D injections. Moreover, the hyperparathyroidism observed in CKD mice was also corrected. X-ray examination and histological sections showed successful osseointegration in these mice. Histomorphometrical analysis revealed that the bone-implant contact (BIC) ratio and bone volume (BV/TV) around the implant were significantly increased in the Vit D-supplementation group. In addition, resistance of the implant, as measured by a push-in method, was significantly improved compared to that in the vehicle group. These results demonstrate that Vit D supplementation is an effective approach to improve the fixation of titanium implants in CKD.

Vitamin D deficiency, insulin resistance, and ventricular hypertrophy in the early stages of chronic kidney disease.

BACKGROUND: Chronic kidney disease (CKD) is associated with markedly increased cardiovascular (CV) risk. This increase is not fully explained by traditional CV risk factors but may in part be mediated by nontraditional risk factors, such as inadequate vitamin D (vit D) levels and insulin resistance (IR). Although IR is shown in nondiabetic CKD, its association with vit D deficiency and vascular disease in this population is unknown and what this study aims to investigate. MATERIALS AND METHODS: The study comprised 67 patients with CKD (eGFR ≥ 30 mL/min) and 15 healthy controls matched for age and sex. The phlogosis indexes, vit D levels, IR, carotid intima-media thickness (cIMT), and left ventricular mass index (LVMI) were measured. RESULTS: In our study, the mean value of LVMI and cIMT was significantly higher in patients with eGFR ≥ 30 mL/min compared with controls (p = 0.037 and p < 0.001). The IR and intact parathyroid hormone (iPTH) levels were increased in CKD patients, whereas the serum levels of vit D were significantly reduced (p = 0.044, p = 0.012, p = 0.038). A positive correlation was found between LVMI and IR (r = 0.704, p = 0.041) and a negative correlation was found between IR and vit D levels (r = -0.238, p = 0.031). CONCLUSIONS: In our study, IR and vit D deficiency were found to be independent predictors of left ventricular hypertrophy and atherosclerotic disease. Vitamin D deficiency and IR are thus associated with increased CV risk. More novel approaches to improving IR and vit D supplementation in the CKD population might lead to potential strategies for preventing excess CV mortality.