Estimated small dense low-density lipoprotein-cholesterol and the risk of kidney and cardiovascular outcomes in diabetic kidney disease.

AIMS: This study aimed to investigate the correlations between estimated small dense low-density lipoprotein-cholesterol (esd-LDL-c) and the development of end-stage kidney disease (ESKD), cardiovascular mortality, and all-cause mortality in individuals with diabetic kidney disease (DKD) or diabetes mellitus (DM) concomitant chronic kidney disease (CKD). METHODS: We analyzed the data from a biopsy-proven DKD cohort conducted at West China Hospital of Sichuan University between 2009 and 2021 (the DKD cohort) and participants with DM and CKD in the National Health and Nutrition Examination Survey (NHANES) 2011-2014 (the NHANES DM-CKD cohort). Cox regression analysis was also used to estimate associations between esd-LDL-c and the incidence of ESKD, cardiovascular mortality, and all-cause mortality. RESULTS: There were 175 ESKD events among 338 participants in the DKD cohort. Patients were divided into three groups based on esd-LDL-c tertiles (T1 < 33.7 mg/dL, T2 ≥ 33.7 mg/dL to <45.9 mg/dL, T3 ≥ 45.9 mg/dL). The highest tertile of esd-LDL-c was associated with ESKD (adjusted HR 2.016, 95% CI 1.144-3.554, p = .015). Furthermore, there were 99 deaths (39 cardiovascular) among 293 participants in the NHANES DM-CKD cohort. Participants were classified into three groups in line with the tertile values of esd-LDL-c in the DKD cohort. The highest tertile of esd-LDL-c was associated with cardiovascular mortality (adjusted HR 3.95, 95% CI 1.3-12, p = .016) and all-cause mortality (adjusted HR 2.37, 95% CI 1.06-5.32, p = .036). CONCLUSIONS: Higher esd-LDL-c was associated with increased risk of ESKD in people with biopsy-proven DKD, and higher cardiovascular and all-cause mortality risk among those with DM-CKD.

Evaluation of Determinants to Achieve Target Urea Reduction Ratio on Maintenance Hemodialysis Patients in Bangladesh.

Among patients with chronic kidney disease stage-5 who are treated with dialysis, the urea clearance during hemodialysis is a determinant of the mortality. Decreased serum albumin, serum calcium but increased phosphorus is associated with reduction of URR and mortality in these patients. This study was to compare two groups Urea Reduction Ratio (URR) and different type of biochemical parameters. URR was aimed to target according to Kidney Disease Outcomes Quality Initiative (KDOQI) guideline. This study was an observational study was carried out in the department of Nephrology. Serum Albumin, serum calcium, phosphate, hemoglobin and pre dialysis urea, post dialysis urea were measured from blood sample. URR was calculated by = (1- postdialysis urea/predialysis urea) × 100. Among the patients who under went hemodialysis, 17.31% patients URR was more than 65.0% and Mean±SD of URR was 67.21±1.9%. On the other hand, 82.68% patients URR was less than 65.0% and Mean±SD of URR was 57.4±5.2%. Most of the Biochemical parameters in this study were significantly different between two groups. Where as, there was no significant difference in Age, Sex, Body Mass Index (BMI). The URR is an accurate indicator, can help determination of adequate dialysis. This study aimed to find out the mean value of the urea reduction ratio and the association of biochemical parameters among End Stage Renal Disease (ESRD) patients on maintenance hemodialysis.

Triglyceride glucose index as a marker of primary patency rate of arteriovenous fistula in diabetic hemodialysis patients.

OBJECTIVE: Arteriovenous fistula (AVF) structures are vital formations used for hemodialysis. Diabetes mellitus (DM) is a critical disease affecting the vascular system. The triglyceride glucose (TyG) index has been shown to be associated with major adverse cardiovascular events in patients with Type 2 DM. In this study, we aimed to investigate the effect of the TyG index on the primary AVF patency of diabetic patients. PATIENTS AND METHODS: Between March 2018 and March 2023, patients with DM who underwent AVF surgery in our clinic due to end-stage renal disease were retrospectively included in this study. The patients who could receive hemodialysis were determined as Group 1, and those who could not were determined as Group 2. RESULTS: A total of 189 patients were included in the study. Those who did not develop AVF primary failure were included in Group 1 [n=138, median age = 59 (22-77) years], and those who did were included in Group 2 [n=51, median age = 63 (20-81) years]. In the multivariate analysis, age >70 years (OR: 0.871, 95% CI: 0.594-0.983, p=0.039), the presence of PAD (OR: 0.582, 95% CI: 0.0.458-0.896, p=0.046), and TyG index (OR: 0.879, 95% CI: 0.591-0.916, p<0.001) were determined as independent predictors for primary AVF failure. CONCLUSIONS: This study demonstrated that the TyG index value, calculated from blood samples taken at the time of hospital admission in hemodialysis patients with diabetes mellitus (DM), is an independent predictor of primary AVF failure following AVF surgery.

Seasonal variation of serum potassium in hemodialysis patients: myth or reality? A narrative review of literature.

Research has shown that patients undergoing hemodialysis experience seasonal variations in their serum potassium levels. There was inconsistent seasonal fluctuation in serum potassium levels among the hemodialysis population across different locations. In the form of narrative review for the first time, the article discusses the seasonal changes of serum potassium in this population and its potential reasons, this article demonstrates that it is primarily attributable to seasonal dietary potassium intake. However, existing studies have not quantified seasonal dietary potassium intake, so the results are still speculative. Furthermore, future research ought to further expound upon the clinical implications of seasonal variations in serum potassium levels among dialysis patients, as well as other influencing mechanisms such as the pathophysiological causes of these seasonal changes, particularly those pertaining to dietary, geographical, and regional factors. These findings contribute to a more thorough interpretation of laboratory results in hemodialysis patients and provide important guidance for their individualized dietary management.

High remnant-cholesterol levels increase the risk for end-stage renal disease: a nationwide, population-based, cohort study.

BACKGROUND: The effect of remnant-cholesterol (remnant-C) on incident end-stage renal disease (ESRD) has not been studied longitudinally. This retrospective cohort study evaluated the association between remnant-C and the development of ESRD in a nationwide Korean cohort. METHODS: Participants in a National Health Insurance Service health examination (n = 3,856,985) were followed up until the onset of ESRD. The median duration of follow-up was 10.3 years. The Martin-Hopkins equation was used to determine low-density lipoprotein cholesterol (LDL-C) levels from directly measured triglyceride, high-density lipoprotein cholesterol (HDL-C), and total cholesterol levels. Remnant-C levels were determined by subtracting HDL-C and LDL-C from total cholesterol. The risk for incident ESRD was calculated for each quartile of remnant-C, adjusting for conventional risk factors such as baseline renal function, comorbidities, and total cholesterol levels. RESULTS: ESRD developed in 11,073 (0.29%) participants. The risk for ESRD exhibited a gradual increase according to higher levels of remnant-C, with a 61% increased risk in the highest quartile than in the lowest (hazard ratio [HR] 1.61 [95% confidence interval (CI) 1.50-1.72]). The elevated risk for ESRD in the highest quartile versus the lowest quartile was more prominent in younger than in older subjects (20-29 years, HR 4.07 [95% CI 2.85-5.83]; 30-39 years, HR 2.39 [95% CI 1.83-3.13]; ≥ 70 years, HR 1.32 [95% CI 1.16-1.51]). In addition, the increased risk for ESRD related to higher remnant-C levels was greater in females than in males. CONCLUSIONS: Independent of conventional risk factors, remnant-C levels were positively associated with incident ESRD, particularly in younger populations and adult females. Reducing remnant-C levels may be a novel preventive strategy against ESRD.

Preanalytical considerations in quantifying circulating miRNAs that predict end-stage kidney disease in diabetes.

Our previous study identified 8 risk and 9 protective plasma miRNAs associated with progression to end-stage kidney disease (ESKD) in diabetes. This study aimed to elucidate preanalytical factors that influence the quantification of circulating miRNAs. Using the EdgeSeq platform, which quantifies 2,002 miRNAs in plasma, including ESKD-associated miRNAs, we compared miRNA profiles in whole plasma versus miRNA profiles in RNA extracted from the same plasma specimens. Less than half of the miRNAs were detected in standard RNA extraction from plasma. Detection of individual and concentrations of miRNAs were much lower when RNA extracted from plasma was quantified by RNA sequencing (RNA-Seq) or quantitative reverse transcription PCR (qRT-PCR) platforms compared with EdgeSeq. Plasma profiles of miRNAs determined by the EdgeSeq platform had excellent reproducibility in assessment and had no variation with age, sex, hemoglobin A1c, BMI, and cryostorage time. The risk ESKD-associated miRNAs were detected and measured accurately only in whole plasma and using the EdgeSeq platform. Protective ESKD-associated miRNAs were detected by all platforms except qRT-PCR; however, correlations among concentrations obtained with different platforms were weak or nonexistent. In conclusion, preanalytical factors have a profound effect on detection and quantification of circulating miRNAs in ESKD in diabetes. Quantification of miRNAs in whole plasma and using the EdgeSeq platform may be the preferable method to study profiles of circulating cell-free miRNAs associated with ESKD and possibly other diseases.

Thromboinflammatory Biomarkers of Cardiorenal Syndrome in Patients With End-Stage Renal Disease.

Cardiovascular disease is a prevalent complication in patients with end-stage renal disease (ESRD) on maintenance hemodialysis. In the ESRD patient population, cardiovascular mortality is 20 times higher compared to the general population. The strong relationship between both illnesses can be explained through cardiorenal syndrome (CRS). CRS encompasses a spectrum of disorders involving both the heart and kidneys in which acute or chronic dysfunction in one organ may induce a similar effect in the other organ. Current literature reveals that inflammation and thrombosis are integral to CRS development. Hence, this study aims to demonstrate whether thromboinflammatory biomarkers and laboratory parameters correlate with ESRD progression and the development of CRS. Ninety-five ESRD patients were recruited at Loyola University Medical Center hemodialysis unit. Epic chart analysis was used to determine patients with CRS. Biomarkers (C-reactive protein, tumor necrosis factor alpha, interleukin-6, Annexin V, L-fatty acid binding protein, monocyte chemoattractant protein 1, nitric oxide, von Willebrand factor, D-dimer, and plasminogen activator inhibitor-1) were profiled using the enzyme-linked immunosorbent assay method in patients with and without CRS in the ESRD cohort. All biomarkers were significantly elevated in ESRD patients compared to normal controls (P < .05) and laboratory parameters, ferritin (521.99 ± 289.33) and PTH (442.91 ± 1.50). Through EPIC chart analysis 47% of ESRD patients have CRS. D-dimer and TNF-α were significantly elevated in patients with CRS compared to patients without CRS. This study suggests that biomarkers, D-dimer, and TNF-α, can be good predictors of CRS in ESRD patients.

Management of serum phosphorus over a 1-year follow-up in patients on peritoneal dialysis prescribed sucroferric oxyhydroxide as part of routine care: a retrospective analysis.

BACKGROUND: Hyperphosphatemia is associated with increased morbidity and mortality in patients with end-stage kidney disease (ESKD). Whereas clinical and observational studies have demonstrated the effectiveness of sucroferric oxyhydroxide (SO) in controlling serum phosphorus (sP) in ESKD, data on the real-world impact of switching to SO in patients on peritoneal dialysis (PD) are limited. In this retrospective database analysis, we examine the impact of SO on sP management over a 1-year period among PD patients prescribed SO as part of routine clinical care. METHODS: We analyzed de-identified data from adults on PD in Fresenius Kidney Care clinics who were prescribed SO monotherapy between May 2018 and December 2019 as part of routine clinical management. Changes from baseline in sP levels, phosphate binder (PB) pill burden, and laboratory parameters were evaluated during the four consecutive 91-day intervals of SO treatment. RESULTS: The mean age of the 402 patients who completed 1 year of SO was 55.2 years at baseline, and they had been on PD for an average of 19.9 months. SO was initiated with no baseline PB recorded in 36.1% of patients, whereas the remaining 257 patients were switched to SO from sevelamer (39.7%), calcium acetate (30.4%), lanthanum (1.2%), ferric citrate (14.0%), or more than one PB (14.8%). Mean sP at baseline was 6.26 mg/dL. After being prescribed SO, the percentage of patients achieving sP ≤ 5.5 mg/dL increased from 32.1% (baseline) to 46.5-54.0% during the 1-year follow-up, whereas the mean number of PB pills taken per day decreased from 7.7 at baseline (among patients on a baseline PB) to 4.6 to 5.4. Serum phosphorus and PB pill burden decreased regardless of changes in residual kidney function over the 12-month period. Similar results were observed for the full cohort (976 patients who either completed or discontinued SO during the 1-year follow-up). CONCLUSIONS: Patients on PD who were prescribed SO as part of routine care for phosphorus management experienced significant reductions in SP and PB pills per day and improvements in sP target achievement, suggesting the effectiveness of SO on SP management with a concurrent reduction in pill burden.

Serum Lipoprotein(a) Levels as a Predictor of Aortic Stiffness in Patients on Long-Term Peritoneal Dialysis.

BACKGROUND Lipoprotein (a) [Lp(a)] is associated with atherosclerosis and cardiovascular mortality in patients with kidney failure. Aortic stiffness (AS), measured primarily by carotid-femoral pulse wave velocity (cfPWV), reflects vascular aging and precedes end-organ failure. This study aimed to evaluate the association between serum Lp(a) levels and cfPWV in patients undergoing peritoneal dialysis (PD). MATERIAL AND METHODS In this cross-sectional study, which included 148 patients with long-term PD for end-stage kidney failure, cfPWV was measured using a cuff-based method. AS was defined as a cfPWV exceeding 10 m/s, and an enzyme-linked immunosorbent assay was used to determine serum Lp(a) levels. Univariate and multivariate regression analyses were performed to identify the clinical correlates of AS. RESULTS There were 32 (21.6%) patients diagnosed with AS. Based on the multivariate logistic regression analysis, the odds ratio for AS was 1.007 (95% confidence interval, 1.003-1.011; P=0.001) for every 1 mg/L increase in Lp(a) levels. Multivariate linear regression analysis showed that Lp(a) (P<0.001), age (P=0.003), waist circumference (P=0.008), systolic blood pressure (P=0.010), and diabetes mellitus (P<0.001) were positively associated with cfPWV. The area under the receiver operating characteristic curve for Lp(a) in differentiating AS from non-AS was 0.770 (95% confidence interval, 0.694-0.835; P<0.0001). CONCLUSIONS Serum Lp(a) level was independently associated with cfPWV and AS in patients with PD.

Association of plasma ceramide with decline in kidney function in patients with type 2 diabetes.

Circulating ceramide levels are dysregulated in kidney disease. However, their associations with rapid decline in kidney function (RDKF) and end-stage kidney disease (ESKD) in patients with type 2 diabetes (T2D) are unknown. In this prospective study of 1746 T2D participants, we examined the association of plasma ceramide Cer16:0, Cer18:0, Cer24:0, and Cer24:1 with RDKF, defined as an estimated glomerular filtration rate (eGFR) decline of 5 ml/min/1.73 m2 per year or greater, and ESKD defined as eGFR <15/min/1.73 m2 for at least 3 months, on dialysis or renal death at follow-up. During a median follow-up period of 7.7 years, 197 patients experienced RDKF. Ceramide Cer24:0 (odds ratio [OR] = 0.71, 95% CI 0.56-0.90) and ratios Cer16:0/Cer24:0 (OR = 3.54 [1.70-7.35]), Cer18:0/Cer24:0 (OR = 1.89 [1.10-3.25]), and Cer24:1/Cer24:0 (OR = 4.01 [1.93-8.31]) significantly associated with RDKF in multivariable analysis; 124 patients developed ESKD. The ratios Cer16:0/Cer24:0 (hazard ratio [HR] = 3.10 [1.44-6.64]) and Cer24:1/Cer24:0 (HR = 4.66 [1.93-11.24]) significantly associated with a higher risk of ESKD. The Cer24:1/Cer24:0 ratio improved risk discrimination for ESKD beyond traditional risk factors by small but statistically significant margin (Harrell C-index difference: 0.01; P = 0.022). A high ceramide risk score also associated with RDKF (OR = 2.28 [1.26-4.13]) compared to lower risk score. In conclusion, specific ceramide levels and their ratios are associated with RDKF and conferred an increased risk of ESKD, independently of traditional risk factors, including baseline renal functions in patients with T2D.

Interferon-Gamma Release Assay Combined with Renal Indicators to Reduce the False-Negativity of Latent Tuberculosis Infection in End-Stage Renal Disease with Hemodialysis Patients.

BACKGROUND: Tuberculosis (TB) is still the main cause of mortality due to a single transfectant, Mycobacterium tuberculosis (MTB). Latent tuberculosis infection (LTBI) is a condition characterized by the presence of tuberculosis (TB) that is not clinically apparent but nonetheless shows a sustained response to MTB. Presently, tuberculin skin test (TST) and interferon gamma (IFN-γ) release assays (IGRAs) are mainly used to detect LTBI via cell-mediated immunity of T-cells. For people with end-stage renal disease (ESRD), the diagnosis of patients infected with MTB is difficult because of T-cell dysfunction. To get more accurate diagnosis results of LTBI, it must compensate for the deficiency of IGRA tests. METHODS: Sixty-seven hemodialysis (HD) patients and 96 non-HD patients were enrolled in this study and the study population is continuously included. IFN-γ levels were measured by the QuantiFERON-TB Gold In-Tube (QFT-GIT) test. Kidney function indicators, blood urea nitrogen (BUN), serum creatinine (Cr), and estimated glomerular filtration rate (eGFR) were used to compensate for the declined IFN-γ levels in the IGRA test. RESULTS: In individuals who were previously undetected, the results of compensation with serum Cr increased by 10.81%, allowing for about 28% more detection, and compensation with eGFR increased by 5.41%, allowing for approximately 14% more detectable potential among them and employing both of them could enhance the prior shortcomings of IGRA tests. when both are used, the maximum compensation results show a sensitivity increase rate of 8.81%, and approximately 23% of patients who were previously undetectable may be found. CONCLUSION: Therefore, the renal function markers which are routine tests for HD patients to compensate for the deficiency of IGRA tests could increase the accuracy of LTBI diagnosis.

Higher N-terminal pro-brain natriuretic peptide level at onset of peritoneal dialysis-related peritonitis is a risk factor for technique failure.

BACKGROUND: Recent studies have suggested that the N-terminal fragment of B-type natriuretic peptide (NT-proBNP) level serve as a significant risk factor for mortality in patients with end-stage renal disease. However, the relationship between NT-proBNP levels and technique failure in peritoneal dialysis-associated peritonitis (PDAP) remains unclear. This study investigated the relationship between NT-proBNP levels at the onset of PDAP and the risk of technique failure in patients with PDAP. METHODS: A retrospective analysis was conducted on patients with PDAP from December 1, 2009, to December 31, 2021, at our peritoneal dialysis center. We recorded all demographic and baseline clinical data at the time of admission for each PDAP episode. Logistic and Cox regression analyses were performed to assess the association between NT-proBNP levels and technique failure. RESULTS: Of 485 PDAP episodes included in this study, 130 episodes of technique failure were observed. Multivariate logistic analysis revealed that hospital stay, Na and NT-proBNP levels, and peritoneal dialysate white blood cell counts on days 3 and 5 were independently associated with technique failure. The receiver operating characteristic curve demonstrated that the NT-proBNP level was a better indicator than the other four variables in indicating technique failure. In the multivariate Cox regression analysis, after adjusting for confounding factors, higher NT-proBNP levels (HR of 3.020, 95% CI 1.771, 5.150, P < 0.001) were associated with PDAP technique failure. CONCLUSIONS: This retrospective study identified the serum NT-proBNP level at the onset of PDAP as an independent risk factor for technique failure in these patients.

Prognosis and factors related to severe secondary hyperparathyroidism in long-term peritoneal dialysis patients.

Secondary hyperparathyroidism (SHPT) can progress to severe SHPT (sSHPT), which affects the survival rate and quality of life of patients. This retrospective cohort study investigated risk factors for sSHPT and the association between SHPT and mortality (all-cause and infection-related) among 771 clinically stable patients (421 male patients; mean age, 51.2 years; median dialysis vintage, 28.3 months) who underwent >3 months of regular peritoneal dialysis (PD) between January 2013 and March 2021. The sSHPT and non-sSHPT groups comprised 75 (9.7%) (median progression, 35 months) and 696 patients, respectively. sSHPT was defined as a serum intact parathyroid hormone (PTH) level >800 pg/mL observed three times after active vitamin D pulse therapy. The influence of sSHPT on the prognosis of and risk factors for sSHPT progression were evaluated using logistic and Cox regression analyses. After adjusting for confounding factors, higher (each 100-pg/mL increase) baseline PTH levels (95% confidence interval (CI) 1.206-1.649, p < .001), longer (each 1-year increase) dialysis vintages (95% CI 1.013-1.060, p = .002), higher concomitant diabetes rates (95% CI 1.375-10.374, p = .010), and lower (each 1-absolute unit decrease) Kt/V values (95% CI 0.859-0.984, p = .015) were independent risk factors for progression to sSHPT in patients on PD. During follow-up, 211 deaths occurred (sSHPT group, n = 35; non-sSHPT group, n = 176). The sSHPT group had significantly higher infection-related mortality rates than the non-sSHPT group (12.0% vs. 4.3%; p < .05), and sSHPT was associated with increased infection-related mortality. In conclusion, patients with sSHPT are at higher risk for death and infection-related mortality than patients without sSHPT.

Risk factors for cardio-cerebrovascular events among patients undergoing continuous ambulatory peritoneal dialysis and their association with serum magnesium.

Serum magnesium levels exceeding 0.9 mmol/L are associated with increased survival rates in patients with CKD. This retrospective study aimed to identify risk factors for cardio-cerebrovascular events among patients receiving continuous ambulatory peritoneal dialysis (CAPD) and to examine their correlations with serum magnesium levels. Sociodemographic data, clinical physiological and biochemical indexes, and cardio-cerebrovascular event data were collected from 189 patients undergoing CAPD. Risk factors associated with cardio-cerebrovascular events were identified by univariate binary logistic regression analysis. Correlations between the risk factors and serum magnesium levels were determined by correlation analysis. Univariate regression analysis identified age, C-reactive protein (CRP), red cell volume distribution width standard deviation, red cell volume distribution width corpuscular volume, serum albumin, serum potassium, serum sodium, serum chlorine, serum magnesium, and serum uric acid as risk factors for cardio-cerebrovascular events. Among them, serum magnesium ≤0.8 mmol/L had the highest odds ratio (3.996). Multivariate regression analysis revealed that serum magnesium was an independent risk factor, while serum UA (<440 µmol/L) was an independent protective factor for cardio-cerebrovascular events. The incidence of cardio-cerebrovascular events differed significantly among patients with different grades of serum magnesium (χ2 = 12.023, p = 0.002), with the highest incidence observed in patients with a serum magnesium concentration <0.8 mmol/L. High serum magnesium levels were correlated with high levels of serum albumin (r = 0.399, p < 0.001), serum potassium (r = 0.423, p < 0.001), and serum uric acid (r = 0.411, p < 0.001), and low levels of CRP (r = -0.279, p < 0.001). In conclusion, low serum magnesium may predict cardio-cerebrovascular events in patients receiving CAPD.

Interleukin-16 is increased in dialysis patients but is not a cardiovascular risk factor.

Oxalate, a uremic toxin that accumulates in dialysis patients, is associated with cardiovascular disease. As oxalate crystals can activate immune cells, we tested the hypothesis that plasma oxalate would be associated with cytokine concentrations and cardiovascular outcomes in dialysis patients. In a cohort of 104 US patients with kidney failure requiring dialysis (cohort 1), we measured 21 inflammatory markers. As IL-16 was the only cytokine to correlate with oxalate, we focused further investigations on IL-16. We searched for associations between concentrations of IL-16 and mortality and cardiovascular events in the 4D cohort (1255 patients, cohort 2) and assessed further associations of IL-16 with other uremic toxins in this cohort. IL-16 levels were positively correlated with pOx concentrations (ρ = 0.39 in cohort 1, r = 0.35 in cohort 2) and were elevated in dialysis patients when compared to healthy individuals. No significant association could be found between IL-16 levels and cardiovascular events or mortality in the 4D cohort. We conclude that the cytokine IL-16 correlates with plasma oxalate concentrations and is substantially increased in patients with kidney failure on dialysis. However, no association could be detected between IL-16 concentrations and cardiovascular disease in the 4D cohort.

Comparative CKD risk prediction using homocitrulline and carbamylated albumin: two circulating markers of protein carbamylation.

BACKGROUND: Protein carbamylation, a post-translational protein modification primarily driven by urea, independently associates with adverse clinical outcomes in patients with CKD. Biomarkers used to quantify carbamylation burden have mainly included carbamylated albumin (C-Alb) and homocitrulline (HCit, carbamylated lysine). In this study, we aimed to compare the prognostic utility of these two markers in order to facilitate comparisons of existing studies employing either marker alone, and to inform future carbamylation studies. METHODS: Both serum C-Alb and free HCit levels were assayed from the same timepoint in 1632 individuals with CKD stages 2-4 enrolled in the prospective Chronic Renal Insufficiency Cohort (CRIC) study. Adjusted Cox proportional hazard models were used to assess risks for the outcomes of death (primary) and end stage kidney disease (ESKD) using each marker. C-statistics, net reclassification improvement, and integrated discrimination improvement were used to compare the prognostic value of each marker. RESULTS: Participant demographics included mean (SD) age 59 (11) years; 702 (43%) females; 700 (43%) white. C-Alb and HCit levels were positively correlated with one another (Pearson correlation coefficient 0.64). Higher C-Alb and HCit levels showed similar increased risk of death (e.g., the adjusted hazard ratio [HR] for death in the 4th carbamylation quartile compared to the 1st was 1.90 (95% confidence interval [CI] 1.35-2.66) for C-Alb, and 1.89 [1.27-2.81] for HCit; and on a continuous scale, the adjusted HR for death using C-Alb was 1.24 [1.11 to 1.39] per standard deviation increase, and 1.27 [1.10-1.46] using HCit). Both biomarkers also had similar HRs for ESKD. The C-statistics were similar when adding each carbamylation biomarker to base models (e.g., for mortality models, the C-statistic was 0.725 [0.707-0.743] with C-Alb and 0.725 [0.707-0.743] with HCit, both compared to a base model 0.723). Similarities were also observed for the net reclassification improvement and integrated discrimination improvement metrics. CONCLUSIONS: C-Alb and HCit had similar performance across multiple prognostic assessments. The markers appear readily comparable in CKD epidemiological studies.

The impact of accessibility to non-calcium-based phosphate binders and calcimimetics on mineral outcomes in patients receiving maintenance hemodialysis: A 10-year retrospective analysis of real-world data.

INTRODUCTION: Hyperphosphatemia and hyperparathyroidism are common in end-stage kidney disease and are associated with poor outcomes. In addition to adequate dialysis, medications are usually required for optimum control of serum phosphate and parathyroid hormone (PTH) levels. The use of calcium-based phosphate binders (CBPBs) and active vitamin D is associated with an increase in serum calcium and worsening vascular calcification. To overcome these limitations, non-calcium-based phosphate binders (NCBPBs) and calcimimetics have been developed. However, the coverage for these new medications remains limited in several parts of the world due to the lack of patient-level outcome data and cost. The present study examined the differences in mineral outcomes between two main categories of healthcare programs that provided different coverage for medications used to control mineral and bone disorders (MBD). The Social Security/Universal Coverage (SS/UC) program covered only CBPBs and active vitamin D, whereas the Civil Servant/State Enterprise (CS/SE) program provided coverage of CBPBs, active vitamin D, NCBPBs, and calcimimetics. METHODS: This 10-year retrospective cohort study examined the differences in mineral outcomes between two healthcare programs in maintenance hemodialysis patients. The differences in serum calcium, phosphate, and PTH levels, as well as the aortic arch calcification score, were analyzed according to dialysis vintage by linear mixed-effects regression analyses. The difference in the composite outcome of severe hyperparathyroidism and parathyroidectomy was analyzed by the Cox-proportional hazard regression model. RESULTS: 714 patients were included in the analyses (full cohort). Of these patients, 563 required at least one type of medication to control MBD (MBD medication subgroup). Serum calcium, phosphate, and the proportions of patients with hypercalcemia and hyperphosphatemia were substantially higher in the SS/UC group compared with the CS/SE group after appropriate adjustments for confounders in both the full cohort and the MBD medication subgroup. These findings were confirmed in propensity-score matched analyses. Higher parathyroid hormone levels and a higher rate of the composite endpoint of severe hyperparathyroidism and parathyroidectomy were also observed in the SS/UC group. A more rapid progression of aortic arch calcification was suggested in the SS/UC group, but between-group changes were not significant. CONCLUSION: Patients under the healthcare program that did not cover the use of NCBPBs and calcimimetics showed higher serum calcium and phosphate levels and a more rapid progression of hyperparathyroidism. The difference in the progression of vascular calcification could not be confirmed in the present study.