Spectrum Of Chronic Kidney Disease Research Articles

All the might of the osteocyte: emerging roles in chronic kidney disease

Osteocytes are the most abundant type of bone cell and play crucial roles in bone health. Osteocytes sense mechanical stress and orchestrate osteoblasts and osteoclasts to maintain bone density and strength. Beyond this, osteocytes have also emerged as key regulators of organ crosstalk, and they function as endocrine organs via their roles in secreting factors that mediate signaling within their neighboring bone cells and in distant tissues. As such, osteocyte dysfunction has been associated with the bone abnormalities seen across a spectrum of chronic kidney disease. Specifically, dysregulated osteocyte morphology and signaling have been observed in the earliest stages of chronic kidney disease and have been suggested to contribute to kidney disease progression. More important, US Food and Drug Administration-approved inhibitors of osteocytic secreted proteins, such as fibroblast growth factor 23 and sclerostin, have been used to treat bone diseases. The present mini review highlights new research that links dysfunctional osteocytes to the pathogenesis of chronic kidney disease mineral and bone disorder.

Rationale and design of an investigator-initiated, multicenter, prospective, placebo-controlled, double-blind, randomized trial to evaluate the effects of finerenone on vascular stiffness and cardiorenal biomarkers in type 2 diabetes and chronic kidney disease (FIVE-STAR)

BackgroundThe overactivation of mineralocorticoid receptor (MR) plays a key pathological role in the progression of cardiovascular and renal diseases by promoting pro-inflammatory and pro-fibrotic signaling. Recently, it has been found that finerenone, a novel nonsteroidal selective MR antagonist, can robustly improve cardiorenal outcomes in patients with type 2 diabetes (T2D) and a wide spectrum of chronic kidney disease (CKD). However, the mechanisms underlying the cardiorenal benefits of finerenone are poorly understood. Further, whether the clinical benefits are mediated by an improvement in vascular stiffness is not confirmed. Therefore, the current study aims to evaluate the effects of finerenone on vascular stiffness as assessed using cardio ankle vascular index (CAVI) and relevant cardiorenal biomarkers in patients with T2D and CKD.MethodsThe Effects of Finerenone on Vascular Stiffness and Cardiorenal Biomarkers in Type 2 Diabetes and Chronic Kidney Disease (FIVE-STAR) is an ongoing, investigator-initiated, multicenter, prospective, placebo-controlled, double-blind, randomized clinical trial in Japan. Its target sample size is 100 subjects. Recruitment will be performed from September 2023 to July 2024. After obtaining informed consent, eligible participants with T2D and CKD (25 mL/min/1.73 m2 ≤ estimated glomerular filtration ratio [eGFR] < 90 mL/min/1.73 m2 and 30 mg/g Cr ≤ urinary albumin-to-creatinine ratio [UACR] < 3500 mg/g Cr) will be equally randomized to receive 24-week treatment with either finerenone (starting dose at 10 mg once daily in participants with a baseline eGFR < 60 mL/min/1.73 m2 or at 20 mg once daily in those with a baseline eGFR ≥ 60 mL/min/1.73 m2) or dose-matched placebo. The primary endpoint is the change from baseline in CAVI at 24 weeks. The secondary endpoints are changes from baseline in UACR at 12 and 24 weeks and relevant serum and urinary biomarkers at 24 weeks. As an exploratory endpoint, proteomic analysis using the Olink® Target 96 panels will be also performed.DiscussionFIVE-STAR is the first trial evaluating the therapeutic impact of finerenone on vascular stiffness and relevant cardiorenal biomarkers in patients with T2D and CKD. This study will provide mechanistic insights on the clinical benefits of finerenone based on recent cardiovascular and renal outcome trials.Trial registration Unique Trial Number, NCT05887817 (https://clinicaltrials.gov/ct2/show/NCT05887817) and jRCTs021230011 (https://jrct.niph.go.jp/latest-detail/jRCTs021230011).

Efficacy of Empagliflozin in Patients With Heart Failure Across Kidney Risk Categories

BackgroundEmpagliflozin reduces the risk of major heart failure outcomes in heart failure with reduced or preserved ejection fraction. ObjectivesThe goal of this study was to evaluate the effect of empagliflozin across the spectrum of chronic kidney disease in a pooled analysis of EMPEROR-Reduced and EMPEROR-Preserved (Empagliflozin Outcome Trial in Patients with Chronic Heart Failure with Reduced or Preserved Ejection Fraction, respectively). MethodsA total of 9,718 patients were grouped into Kidney Disease Improving Global Outcomes (KDIGO) categories based on estimated glomerular filtration rate (eGFR) and urine albumin-to-creatinine ratio into low-, moderate-, high-, and very–high-risk categories, comprising 32.0%, 29.1%, 21.9%, and 17.0% of the participants, respectively. ResultsIn the placebo arm, when compared with lower risk categories, patients at higher risk experienced a slower rate of decline in eGFR, but a higher risk of a composite kidney event. Empagliflozin reduced the risk of cardiovascular death or heart failure hospitalizations similarly in all KDIGO categories (HR: 0.81; 95% CI: 0.66-1.01 for low-; HR: 0.63; 95% CI: 0.52-0.76 for moderate-; HR: 0.82; 95% CI: 0.68-0.98 for high-; and HR: 0.84; 95% CI: 0.71-1.01 for very–high-risk groups; P trend = 0.30). Empagliflozin reduced the rate of decline in eGFR whether it was estimated by chronic slope, total slope, or unconfounded slope. When compared with the unconfounded slope, the magnitude of the effect on chronic slope was larger, and the effect on total slope was smaller. In EMPEROR-Reduced, patients at lowest risk experienced the largest effect of empagliflozin on eGFR slope; this pattern was not observed in EMPEROR-Preserved. ConclusionsThe benefit of empagliflozin on major heart failure events was not influenced by KDIGO categories. The magnitude of the renal effects of the drug depended on the approach used to calculate eGFR slopes.

Adrenal functional reserve in the full spectrum of chronic kidney disease.

Altered cortisol levels have been associated with an increase in mortality and a decrease in health-related quality of life in patients with chronic kidney disease (CKD); however, adrenal response to adrenocorticotropic hormone (ACTH) stimulation test has not been evaluated in patients with stage 3a to 5 CKD with and without renal replacement therapy (RRT). To evaluate adrenal function in patients with CKD. Adults with CKD underwent a low-dose cosyntropin stimulation test (1 µg synthetic ACTH), with serum cortisol levels being measured at 0, +30 and +60 minutes post-test. Sixty participants with stage 3, 4 and 5 CKD (with and without RRT) were included. None of the patients had adrenal insufficiency (AI). The correlation observed between cortisol concentration at baseline and 30 minutes and 1 hour after stimulation and glomerular filtration rate (GFR) was negative and statistically significant (r: -0.39 [p = 0.002], r: -0.363 [p = 0.004], r: -0.4 [p = 0.002], respectively). Since CKD early stages, cortisol levels increase as GFR decreases. Therefore, we conclude that systematic screening for AI is not necessary in CKD patients.

Longitudinal Patterns of Renal Function in Antineutrophil Cytoplasmic Antibody-Associated Vasculitis.

A spectrum of chronic kidney disease (CKD) and end-stage renal disease (ESRD) may occur in antineutrophil cytoplasmic antibody-associated vasculitis (AAV). The longitudinal trajectory of renal function in AAV is poorly understood. Patients with ≥2 creatinine measurements, including at baseline (±30 days of treatment initiation), were included from the Mass General Brigham AAV Cohort. We calculated estimated glomerular filtration rate (eGFR). We incorporated longitudinal changes in eGFR into a group-based trajectory model to identify patients with similar patterns of change in renal function. The chi-square test and the Kruskal-Wallis test were used to evaluate differences between groups in categorical variables and non-normally distributed continuous variables, respectively. In 255 AAV patients, we identified 4 renal trajectory groups: rapid decline (n=20), impaired (n=82), preserved (n=129), and recovery (n=24). The rapid decline and impaired groups had greater baseline comorbidity (P=0.01) and lower prevasculitis eGFR (P=0.02). Clinically significant CKD (eGFR <60 ml/minute/1.73 m2 ) persisted over 5 years in >75% of the impaired group, compared to <40% of patients in the preserved group (P < 0.001). ESRD occurred most frequently in the rapid decline (100%), followed by the impaired and preserved groups (7% each). Baseline AAV renal involvement was present prior to 95% of ESRD. However, ESRD etiology varied, with 90% of rapid-onset ESRD attributed to vasculitis, versus 17-44% in impaired or preserved groups (P=0.001). We identified 4 longitudinal patterns of renal function after AAV diagnosis. Our findings highlight the burden of CKD in AAV and provide a framework for future research into personalized care in this vulnerable population.

Approaches to the identification and management of depression in people living with chronic kidney disease: A scoping review of 860 papers.

Depression is prevalent across the spectrum of Chronic Kidney Disease and associated with poorer outcomes. There is limited evidence regarding the most effective interventions and care pathways for depression in Chronic Kidney Disease. To investigate how depression is identified and managed in adults with Chronic Kidney Disease. Scoping review. Systematic search of eight databases with pre-defined inclusion criteria. Data relevant to the identification and/or management of depression in adults with Chronic Kidney Disease were extracted. Of 2147 articles identified, 860 were included. Depression was most identified using self-report screening tools (n = 716 studies, 85.3%), with versions of the Beck Depression Inventory (n = 283, 33.7%) being the most common. A total of 123 studies included data on the management of depression, with nonpharmacological interventions being more frequently studied (n = 55, 45%). Cognitive Behavioural Therapy (n = 15) was the most common nonpharmacological intervention, which was found to have a significant effect on depressive symptoms compared to controls (n = 10). However, how such approaches could be implemented as part of routine care was not clear. There was limited evidence for antidepressants use in people with Chronic Kidney Disease albeit in a limited number of studies. Depression is commonly identified using validated screening tools albeit differences exist in reporting practices. Evidence regarding the management of depression is mixed and requires better-quality trials of both pharmacological and nonpharmacological approaches. Understanding which clinical care pathways are used and their evidence, may help facilitate the development of kidney care specific guidelines for the identification and management of depression.

Front Cover

The outside front cover image is based on the Original Article Finerenone in patients across the spectrum of chronic kidney disease and type 2 diabetes by glucagon-like peptide-1 receptor agonist use by Peter Rossing MD et al., https://doi.org/10.1111/dom.14883.

Prevalence of low bone mineral density (T-score ≤ - 2.5) in the whole spectrum of chronic kidney disease: a systematic review and meta-analysis.

The prevalence of low bone mineral density (LBMD) in people with chronic kidney disease (CKD) remains unknown. We identified a high prevalence of LBMD in CKD population. Thus, public health strategies should include efforts to prevent, early detect, and manage LBMD in CKD patients, especially in patients undergoing kidney replacement therapy. Mineral and bone disorders are common among patients with CKD, which affects bone mineral density. We conducted a systematic review and meta-analysis to estimate the prevalence of low bone mineral density (LBMD) in adults with CKD. We searched MEDLINE, EMBASE, Web of Science, CINAHL, and LILACS databases from inception to February 2021. Observational studies that reported the prevalence of LBMD in adults with CKD stages 3a-5D were included. The LBMD was defined according to the World Health Organization criterion (T-score ≤ - 2.5). Random-effect model meta-analyses were used to estimate the pooled prevalence of LBMD. Meta-regressions and subgroup analyses were conducted for stages of CKD, dialysis modality, gender, bone sites and morphology, and geographical region. This study was registered in PROSPERO, number CRD42020211077. One-hundred and fifty-three studies with 78,092 patients were included. The pooled global prevalence of LBMD in CKD was 24.5% (95% CI, 21.3 - 27.8%). Subgroup analyses indicated a higher prevalence of LBMD in dialysis patients (30%, 95% CI 25 - 35%) compared with non-dialysis CKD patients (12%, 95% CI 8 - 16%), cortical bone sites (28%, 95% CI 23 - 35%) relative to trabecular sites (19%, 95% CI 14 - 24%), while similar estimates in the European and the Asiatic continents (26%, 95% CI 21 - 30% vs 25%, 95% CI 21 - 29). The prevalence of LBMD in CKD patients is high, particularly in those undergoing dialysis and in cortical bone sites. Therefore, efforts to early diagnosis and management strategies should be implemented in clinical routine for an epidemiological control of LBMD in CKD patients.

A-22 | Predictors of 1-Year Mortality in 6656 Chronic Kidney Disease Patients Across Entire Spectrum of Coronary Artery Disease

There is limited data on outcomes of coronary artery disease (CAD) patients who undergo percutaneous coronary intervention (PCI) across the whole spectrum of chronic kidney disease (CKD). Hence we investigated the determinants of one-year post PCI mortality in this group.

Emerging Patient-Centered Concepts in Pain Among Adults With Chronic Kidney Disease, Maintenance Dialysis, and Kidney Transplant

Patient reports of moderate to severe pain are common across the spectrum of chronic kidney disease. The synergistic effects of comorbid depression and anxiety can lead to maladaptive coping responses to pain, namely pain catastrophizing and illness-related post-traumatic stress disorder. If underlying depression and anxiety and associated maladaptive coping responses are not treated, patients can experience an increased perception of pain, worsened disability, decreased quality of life, withdrawal from social activities, and increased morbidity and mortality. Meanwhile, interest in nonpharmacologic treatments for pain that targets coping as well as comorbid anxiety and depression has been increasing, particularly given the significant societal damage that has resulted from the opioid epidemic. Evidence-based, nonpharmacologic treatments have shown promise in treating pain in areas outside of nephrology. Currently, little is known about the effects of these treatments among adults with CKD, and particularly end-stage kidney disease, when chronic pain can become debilitating. In this review, we examine patient-centered concepts related to pain that have received little attention in the nephrology literature. We also describe emerging areas of research, including omics technologies for biomarker discovery and advanced symptom clustering methods for symptom phenotyping, which may be useful to future kidney disease research and treatment.

Spectrum of Chronic Kidney Disease in Children less Than 15 Years of Age at Tertiary Care Hospital

Spectrum of Chronic Kidney Disease in Children less Than 15 Years of Age at Tertiary Care Hospital

P1383ECONOMIC BENEFITS OF SWITCHING FROM INTRAVENOUS TO SUBCUTANEOUS ERTHROPOIESIS-SIMULATING AGENTS THERAPY FOR MANAGEMENT OF ANEMIA IN HEMODIALYSIS PATIENTS

Abstract Background and Aims Erythropoiesis stimulating agents (ESA’s) were introduced in the treatment of anemia in 1989 and it immediately led to a marked decline in the number of blood transfusions and improved quality of life in patients across the spectrum of chronic kidney disease. Several studies from the mid 1990s have shown that the required doses of Epoetin alpha were lower when administered subcutaneously (SQ). These studies led to guidelines by NKF (1997) and KDOQI (2001) recommending the use of SQ over intravenous (IV) as considerable cost savings could be achieved without compromising care. The rise in the reported cases of pure red cell aplasia (PRCA) led to a change in guidelines in 2006 and led to units changing exclusively to IV route. It was subsequently identified that polysorbate 80 from uncoated rubber stoppers in pre-filled syringes rather than the route of administration was the most plausible cause of PRCA. However, higher doses of ESAs, have been associated with adverse health outcomes across all hematocrit categories in hemodialysis patients. While the current practice is to administer ESAs to patients through IV route, SQ ESAs achieve the same target hemoglobin level at a reduced dose and cost. Given the dose -sparing advantages of SQ Epoetin alpha administration, we decided to gradually transition our patients to SQ and examined the cost of IV versus SQ treatment. The objective of our study was to determine the economic benefit of the change in the route of administration from IV to SQ ESA in hemodialysis patients. Method We conducted a retrospective cohort study in 215 hemodialysis patients who transitioned from IV Epoetin alfa to SQ at four hemodialysis sites in the province of Saskatchewan, Canada from September 2014 to July 2017. The dose and cost of different routes of Epoetin alfa administration per patient per month was calculated. Also, blood hemoglobin, markers of erythropoiesis (transferrin saturation and Ferritin), IV iron dose and cost were determined in relation to route of Epoetin alfa administration. The dependent t-test was used to compare mean variables between pre-switch and post-switch period. Differences in variables across three serum hemoglobin ranges (&amp;lt;95, 95-115, &amp;gt;115 gram/liter) were assessed using the independent t-test. Results The mean Epoetin alfa doses per patient per month (47,327.9±33,133.0 international unit) during pre-switch (IV) period were greater than of post-switch (SQ) period (34,253±24,858.1), a decrease of 27.62% (p&amp;lt;0.001). The mean hemoglobin concentration for patients in both periods remained stable (103.3±9.2 versus 104.3±13.3, p=0.34) and within the target range. The reduction in the dose of Epoetin alfa per patient per month (IU± standard deviation) upon conversion remained similar (IV versus SQ) in all the subcategories: hemoglobin &amp;lt;95 g/L (65,941 versus 52,717), hemoglobin 95-115g/L (42,120 versus 29,619) and (35,289 versus 17,651) for hemoglobin &amp;gt;115 g/L. There were no significant differences in transferrin saturation, Ferritin and IV iron dose and cost between the two study periods. The mean cost (CAD± SD) of Epoetin alfa per patient per month decreased from 674.4±477.4 pre-switch to 484.8±354.3 post-switch (p&amp;lt;0.001), a decrease of 28.11%; whereas, the cost of IV iron remained similar in pre- and post-switch period. Conclusion The (mean) cost of Epoetin alfa per patient per year in our study when given IV was $ 8,088 (CAD) and once converted to SQ was $ 5,817 (CAD) while achieving equivalent hemoglobin levels, a saving of $ 2271 (CAD) per year. Based on these values, if we extrapolate our savings to 900 prevalent patients to SQ Epoetin alfa we can realize a cost saving of $2,043,900 per year. Conversion of Epoetin alfa from IV to SQ led to substantial cost savings at our hemodialysis units.

SO012RENOPROTECTIVE EFFECTS OF FEBUXOSTAT AND ALLOPURINOL IN PATIENTS WITH HYPERURICEMIA AND CHRONIC KIDNEY DISEASES: A META-ANALYSIS

Abstract Background and Aims Hyperuricemia is associated with rapid deterioration of renal function in patients with chronic kidney disease (CKD). The two most common urate-lowering drugs available in the market are allopurinol and febuxostat. Randomized controlled trials (RTCs) have shown that the individual drugs have potential to slow down progression of renal function in patients with chronic kidney disease (CKD) and hyperuricemia. However, it is unclear which drug is more effective because of insufficient direct comparison between the two. Hence our study aims to perform a meta-analysis of RCTs to assess the renoprotective and urate-lowering effects between the two drugs in patients with CKD and hyperuricemia. Method A comprehensive literature search of randomized controlled trials using PubMed was performed with the following search terms: febuxostat, allopurinol, chronic kidney disease, renoprotection. Four prospective RCTs were selected and analyzed using Cochrane Revman v5.3. Outcomes assessed were change in serum creatinine, estimated glomerular filtration rate (eGFR), proteinuria and serum uric acid levels from baseline to 3 months post-initiation of therapy. Results Four relevant trials comprising of 486 patients were selected - 247 patients treated with febuxostat and 239 patients with allopurinol. No significant differences were found in the changes in serum creatinine (mean difference -0.04; CI -0.15, 0.07; P = 0.51) and eGFR (mean difference 1.57; CI -0.83, 3.97; P = 0.20) from baseline to 3 months between the febuxostat and allopurinol group. Decrease in proteinuria was significantly observed more in the febuxostat group (mean difference -50.13; CI -90.54; -9.71, P = 0.02). Similarly, serum uric acid levels were significantly more reduced in the febuxostat group (mean difference -1.11; CI -1.53, -0.68, P &amp;lt; 0.00001). Conclusion Our study showed that febuxostat is non-inferior in terms of delaying renal function decline (as measured by eGFR) but it offers a better anti-proteinuric as well as a urate-lowering effect. However, more studies are needed to assess the efficacy of febuxostat across the spectrum of chronic kidney disease, including those requiring hemodialysis.

The systemic microcirculation in dialysis populations.

In a rapidly expanding population of patients with chronic kidney disease, including 2million people requiring renal replacement therapy, cardiovascular mortality is 15 times greater than the general population. In addition to traditional cardiovascular risk factors, more poorly defined risks related to uremia and its treatments appear to contribute to this exaggerated risk. In this context, the microcirculation may play an important early role in cardiovascular disease associated with chronic kidney disease. Experimentally, the uremic environment and dialysis have been linked to multiple pathways causing microvascular dysfunction. Coronary microvascular dysfunction is reflected in remote and more easily studied vascular beds such as the skin. There is increasing evidence for a correlation between systemic microvascular dysfunction and adverse cardiovascular outcomes. Systemic microcirculatory changes have not been extensively investigated across the spectrum of chronic kidney disease. Recent advances in non-invasive techniques studying the microcirculation in vivo in man are increasing the data available particularly in patients on hemodialysis. Here, we review current knowledge of the systemic microcirculation in dialysis populations, explore whether non-invasive techniques to study its function could be used to detect early stage cardiovascular disease, address challenges faced in studying this patient cohort and identify potential future avenues for research.

Sclerostin within the chronic kidney disease spectrum

Sclerostin is sometimes presented as a promising biomarker in assessing bone health both in the general population and chronic kidney disease patients. However, it is still unclear whether it has any true added value compared to existing bone biomarkers in predicting bone turnover and/or bone density in chronic kidney disease patients. A wealth of papers has been published to evaluate the association between sclerostin and vascular calcifications development or even as prognostic biomarker for mortality, but often with conflicting results. Standardization and harmonization of analytical techniques is a prerequisite to advance clinical knowledge in sclerostin.

Spectrum of chronic kidney disease in China: A national study based on hospitalized patients from 2010 to 2015.

To investigate the spectrum of chronic kidney disease (CKD) in China. We used a large national in-patient database covering 878 class three hospitals and involving 64.7 million adult patients in China from 2010 to 2015. The class 3 hospital in China is ranked as the top tier of medical system in China with at least 500 beds and the accreditation from health authorities. The specific causes of CKD were extracted from the International Classification of Diseases-10 codes of discharge diagnoses. A total of 4.5% of hospitalized patients (1.8 million) were identified as CKD, with an increased percentage from 2010 (3.7%) to 2015 (4.7%). Increasing trends of diabetic kidney disease and hypertensive nephropathy were observed from 2010 to 2015 (19.5% vs 24.3% and 11.5% vs 15.9%, respectively), especially for urban residents from north China. The proportion of obstructive nephropathy also increased gradually (10.3% in 2010 vs 15.6% in 2015) and constituted another important cause of CKD for patients, especially for those from south China and rural residents. The spectrum of CKD is changing in China, with variations over time and geographic regions, which has implication regarding developing the prevention strategy of CKD.

Association of Bone Mineral Density With Fractures Across the Spectrum of Chronic Kidney Disease: The Regina CKD-MBD Study.

Background:Recent studies have demonstrated that measurement of areal bone mineral density by dual-energy x-ray absorptiometry (DXA) predicts fractures in patients with chronic kidney disease (CKD). However, whether fracture risk prediction through bone mineral density (BMD) is enhanced due to the assessment of biochemical markers of chronic kidney disease and mineral and bone disease (CKD-MBD) or clinical risk factors is not clear. We hypothesized that in a select cohort of patients managed in a CKD clinic, that combining T-Scores with biochemical markers would optimize fracture discrimination than using DXA alone.Objective:To examine the relationships among BMD, biochemical markers of CKD-MBD, and fracture risk across Kidney Disease Improving Global Outcomes (KDIGO) glomerular filtration rate (GFR) categories G3a to G5.Design:Retrospective study.Setting:Patients were recruited from the multidisciplinary CKD clinic, Regina General Hospital, Canada.Patients:A total of 374 patients who received a DXA scan upon initial referral to Regina Multidisciplinary CKD Program from January 31, 2001 to January 31, 2010, were included in this study. The patients were followed for a total of 5 years.Methods:We conducted a retrospective review of 374 consecutive patients who underwent DXA imaging at the point of entry into our multidisciplinary CKD program. Areal BMD, T- and Z-Scores were obtained at the lumbar spine, total hip, mean of left and right femoral neck, and the one-third radius. We collected data on demographic, cross-sectional biochemical markers of mineral metabolism and fractures (identified through self-reported questionnaires, hospital electronic medical records, and physician billing records). We were able to gather data on 8/11 variables of Fracture Risk Assessment (FRAX) tool.Results:In our cohort, 14.3% of GFR categories G3a and G3b, 15.7% of GFR category G4, and 19.7% of GFR category G5 experienced a clinical fracture during the study period. On multivariate analysis, each decline of 1.0 SD in total hip BMD T-Score was associated with a significant increase in the risk of fracture (OR = 1.46, 95% confidence interval [CI], 1.12-1.89). Adding CKD-MBD markers and clinical risk factors did not further contribute to the model. Low BMD was the only independent risk factor for fracture in patients with CKD.Limitations:Self-reporting by patients and administrative records were used to identify fractures. We did not perform spine imaging to ascertain morphometric vertebral fractures. We were unable to gather all 11 variables of FRAX score and information on ethnicity. We were unable to capture site of fracture (hips, spine, etc) from billing records. Albumin excretion rates were not collected at baseline. Treatment of the underlying bone disease with pharmacotherapeutic agents may have attenuated patients’ fracture risk and thus underestimated the association between BMD and future fracture.Conclusions:Our findings confirm that BMD predicts fracture. The addition of cross-sectional CKD-MBD parameters and clinical risk factors to BMD did not add to fracture prediction. Prospective studies should investigate the utility of longitudinal biochemical markers on improving fracture risk assessment.

Review on the Utility of Trabecular Bone Score, a Surrogate of Bone Micro-architecture, in the Chronic Kidney Disease Spectrum and in Kidney Transplant Recipients

Chronic kidney disease (CKD) is defined as abnormalities of kidney structure or function, present for >3 months, with implications for, among others, bone health. Advanced stages of CKD have an increased risk of fragility fractures. Trabecular bone score (TBS) is a relatively new gray-level textural parameter, which provides information on bone microarchitecture and has been shown to be a good predictor of fragility fractures independently of bone density and clinical risk factors. We aimed to review the scientific literature on TBS and its utility along the CKD spectrum and in kidney transplant recipients. In total, eight articles had investigated this topic: one article in patients with reduced kidney function, two in patients on hemodialysis, and five in kidney transplant recipients. In general, all the studies had shown an association between lower values of TBS and reduced kidney function; or lower TBS values among the hemodialysis or kidney transplant patients compared to healthy controls. Moreover, TBS was shown to be a good and independent predictor of fragility fractures in patients with CKD or who underwent kidney transplantation. TBS postulates itself as a valuable marker to be used in clinical practice as an assessor of bone microarchitecture and fracture risk predictor in these specific populations. However, evidence is to some extent limited and larger follow-up case-control studies would help to further investigate the TBS utility in the management of bone health damage and increased fracture risk in patients with CKD or kidney transplant.

Echocardiographic parameters and renal outcomes in patients with preserved renal function, and mild- moderate CKD

BackgroundEchocardiographic characteristics across the spectrum of chronic kidney disease (CKD) have not been well described. We assessed the echocardiographic characteristics of patients with preserved renal function and mild or moderate CKD referred for echocardiography and determined whether echocardiographic parameters of left ventricular (LV) and right ventricular (RV) structure and function were associated with changes in renal function and mortality.MethodsThis retrospective cohort study enrolled all adult patients who had at least one trans-thoracic echocardiography between 2004 and 2014 in our institution. The composite outcome of doubling of serum creatinine or initiation of maintenance dialysis or kidney transplantation was the primary outcome. Mortality was the secondary outcome.Results29,219 patients were included. Patients with worse renal function had higher prevalence of structural and functional LV and RV abnormalities. Higher estimated glomerular filtration rate (eGFR) was independently associated with preserved LV ejection fraction, preserved RV systolic function, and lower LV mass, left atrial diameter, pulmonary artery pressure, and right atrial pressure, as well as normal RV structure. 1041 composite renal events were observed. 8780 patients died during the follow-up. Pulmonary artery pressure and the RV, but not the LV, echocardiographic parameters were independently associated with the composite renal outcome. In contrast, RV systolic function, RV dilation or hypertrophy, LV ejection fraction group, LV diameter quartile, and pulmonary artery pressure quartile were independently associated with all-cause mortality.ConclusionsEchocardiographic abnormalities are frequent even in early CKD. Echocardiographic assessment particularly of the RV may provide useful information for the care of patients with CKD.

Strategies to manage cardiovascular risk in chronic kidney disease.

Cardiovascular disease (CVD) remains the leading cause of death across the spectrum of chronic kidney disease (CKD), including CKD not requiring dialysis and for patients requiring dialysis or kidney transplantation. There is a high prevalence of ‘conventional’ cardiovascular risk factors in patients with CKD such as hypertension, dyslipidaemia, diabetes mellitus, smoking, low physical activity/obesity and prior cardiovascular events. Many risk factors contribute to the aetiology and pathogenesis of CKD or are shared risk factors for CKD progression [1]. Furthermore, there are contributors to accelerated CVD specific to, or exaggerated in CKD. Examples include left ventricular hypertrophy (LVH), fluid and electrolyte shifts, proteinuria, functional vitamin D deficiency, hyperphosphataemia, chronic inflammation, vascular stiffness and/or vascular calcification. There are multiple other putative mechanisms for accelerated CVD in CKD patients, identified by phenotyping using state of the art imaging, physiological studies and molecular biology, although these are yet to translate to clinical practice. This NDT Digest will discuss the current clinical evidence for addressing CVD risk in CKD.