Non-dialysis Dependent Chronic Kidney Disease Patients Research Articles

Prognostic effect of masked morning hypertension in Chinese inpatients with non-dialysis chronic kidney disease: A multi-center retrospective study.

This study aimed to elucidate the prognostic role of Masked Morning Hypertension (MMH) in non-dialysis-dependent chronic kidney disease (NDD-CKD). 2,130 NDD-CKD patients of inpatient department were categorized into four blood pressure groups: clinical normotension (CH-), clinical hypertension (CH+) with morning hypertension (MH+), and without MH+ (MH-) respectively. The correlation between these four blood pressure types and the primary (all-cause mortality) and secondary endpoints (cardio-cerebrovascular disease [CVD] and end-stage kidney disease [ESKD]) was analyzed. The prevalences of morning hypertension and masked morning hypertension were 47.4% and 14.98%, respectively. Morning hypertension independently increased the risk of all-cause mortality (P=0.004) and CVD (P<0.001) but not ESKD (P=0.092). Masked morning hypertension was associated with heightened all-cause mortality (HR = 4.22, 95% CI = 1.31-13.59; P=0.02) and CVD events (HR = 5.14, 95% CI = 1.37-19.23; P=0.02), with no significant association with ESKD (HR = 1.18, 95% CI = 0.65-2.15; P=0.60). When considering non-CVD deaths as a competing risk factor, a high cumulative incidence of CVD events was observed in the masked morning hypertension group (HR = 5.16, 95% CI = 1.39-19.08). MMH is an independent risk factor for all-cause mortality and combined cardiovascular and cerebrovascular events in NDD-CKD patients, underscoring its prognostic significance. This highlights the need for comprehensive management of morning hypertension in this population.

Humoral Response Following 3 Doses of mRNA COVID-19 Vaccines in Patients With Non-Dialysis-Dependent CKD: An Observational Study.

Chronic kidney disease (CKD) is associated with a lower serologic response to vaccination compared to the general population. There is limited information regarding the serologic response to coronavirus disease 2019 (COVID-19) vaccination in the non-dialysis-dependent CKD (NDD-CKD) population, particularly after the third dose and whether this response varies by estimated glomerular filtration rate (eGFR). The NDD-CKD (G1-G5) patients who received 3 doses of mRNA COVID-19 vaccines were recruited from renal clinics within British Columbia and Ontario, Canada. Between August 27, 2021, and November 30, 2022, blood samples were collected serially for serological testing every 3 months within a 9-month follow-up period. The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) anti-spike, anti-receptor binding domain (RBD), and anti-nucleocapsid protein (NP) levels were determined by enzyme-linked immunosorbent assay (ELISA). Among 285 NDD-CKD patients, the median age was 67 (interquartile range [IQR], 52-77) years, 58% were men, 48% received BNT162b2 as their third dose, 22% were on immunosuppressive treatment, and COVID-19 infection by anti-NP seropositivity was observed in 37 of 285 (13%) patients. Following the third dose, anti-spike and anti-RBD levels peaked at 2 months, with geometric mean levels at 1131 and 1672 binding antibody units per milliliter (BAU/mL), respectively, and seropositivity rates above 93% and 85%, respectively, over the 9-month follow-up period. There was no association between eGFR or urine albumin-creatinine ratio (ACR) with mounting a robust antibody response or in antibody levels over time. The NDD-CKD patients on immunosuppressive treatment were less likely to mount a robust anti-spike response in univariable (odds ratio [OR] 0.43, 95% confidence interval [CI]: 0.20, 0.93) and multivariable (OR 0.52, 95% CI: 0.25, 1.10) analyses. An interaction between age, immunoglobulin G (IgG) antibody levels, and time was observed in both unadjusted (anti-spike: P = .005; anti-RBD: P = .03) and adjusted (anti-spike: P = .004; anti-RBD: P = .03) models, with older individuals having a more pronounced decline in antibody levels over time. Most NDD-CKD patients were seropositive for anti-spike and anti-RBD after 3 doses of mRNA COVID-19 vaccines and we did not observe any differences in the antibody response by eGFR.

Do Alpha-Ketoanalogues Slow Down Disease Progression in Non-Dialysis Dependent Chronic Kidney Disease?

Objective: To observe the effectiveness of keto-analogues in slowing down the disease progression in non-dialysis dependent CKD patients.Study Design: Quasi-experimental study.Place and Duration of Study: The study was carried out at Nephrology Department of Combined Military Hospital (CMH), Peshawar, Pakistan from August 2022 to 28 February 2023.Methods: Data was collected on 290 kidney disease improving global outcomes (KDIGO) stage 3 and 4 CKD patients through non-probability consecutive sampling technique. The cohort was divided into group A (Low protein diet) and B (ketodiet). Group A received low protein diet in addition to standard chronic disease treatment while Group B was labelled as keto-diet group which received ketoanalogues in addition to low protein diet and standard chronic kidney disease treatment. Baseline and six months eGFR was calculated and compared for both groups. SPSS version 23.00 was used for data analysis. The P value ≤ 0.05 was considered significant.Results: 286 patients aged 51.84±18.127 were selected for our study. 188(65.73%) were males while females were 98 (34.26%). There were 142 (50.34%) and 144(50.34%) patients in group A and B respectively. Duration of CKD in group A and B was 6.45±2.55 and 6.49±1.75 years respectively. The means difference of eGFR in group A (low protein diet) at baseline and after six months was 3.64±1.09mL/ min/ 1.73m2 while that of group B was 1.48±0.41 mL/ min/ 1.73m2 (P-value&lt;0.000). Conclusion: Ketoanalogues is an emerging therapy which slows down disease progression in non-dialysis dependent CKD patients. Although its use is recommended by some clinicians in CKD stage 3 and 4 non-dialysis dependent but still controversial.&#x0D; How to cite this: Saeed B, Khayam, Afridi Z, Ullah MS. Do Alpha-Ketoanalogues Slow Down Disease Progression in Non-Dialysis Dependent Chronic Kidney Disease?. Life and Science. 2023; 4(4): 427-431. doi: http://doi.org/10.37185/LnS.1.1.407

#2560 HEMOGLOBIN VARIABILITY AND ADVERSE CLINICAL EVENTS IN PATIENTS WITH NON-DIALYSIS-DEPENDENT CHRONIC KIDNEY DISEASE AND ANEMIA IN CONTINUOUS CARE

Abstract Background and Aims Anemia management in non-dialysis dependent chronic kidney disease (NDD-CKD) patients has attracted attention with the introduction of new treatment options, such as prolyl hydroxylase domain enzyme inhibitors (HIF-PHI). However, studies reporting comprehensive information on anemia management in NDD-CKD patients are limited. While previous studies reported increased risks of adverse clinical events associated with hemoglobin (Hb) fluctuation in hemodialysis patients, limited information is available in NDD-CKD patients. Method A retrospective cohort study was performed using a Japanese nationwide electronic medical record-based hospital database. Patients with stage ≥3a NDD-CKD, aged ≥18 years, and at least one recorded Hb &amp;lt;11 g/dL between January 1st 2013 and April 30th 2021 were included. Patients already receiving any anemia treatment (erythropoiesis stimulating agent (ESA), iron, or HIF-PHI) were excluded. Hb levels were collected at the index date (the date of the first recorded Hb &amp;lt;11 g/dL) and during the follow-up period. Clinical events included all-cause death, cardiovascular (CV) events (myocardial infarction, unstable angina pectoris, stroke, or hospitalization for heart failure), dialysis introduction, and red-blood-cell transfusion. Time-dependent Cox proportional hazard models, adjusted by clinically relevant variables were applied to assess the risk of clinical events associated with transitioning Hb fluctuation patterns, categorized into six groups: within the target Hb range (11–13 g/dL); consistently below the target (low); consistently above the target (high); low-amplitude fluctuation around the upper limit of the target (LAH); low-amplitude fluctuation around the lower limit of the target (LAL); and, high amplitude fluctuation across the target (HA). Results Of 162,170 patients with CKD, 26,626 (16.4%) NDD-CKD patients with Hb &amp;lt;11 g/dL were identified (median follow-up length, 1.9 years). The mean age was 75.9 years, and 37.8% were female. In overall patients, the mean (±SD) Hb levels at index and at 3, 6, and 12 months of follow up were 9.9±1.2 g/dL, 10.6±1.5 g/dL, 10.8±1.6 g/dL, and 10.9±1.6 g/dL, respectively. The proportion of patients with Hb &amp;lt;10 g/dL at index and at 12 months were 34.3% and 23.9%, respectively. In the subgroup of patients treated with ESA or HIF-PHI (n = 8,876), the mean Hb (±SD) levels had increased from 9.3±1.3 g/dL to 10.3±1.5 g/dL at 3 months, 10.5±1.5 g/dL at 6 months, and 10.6±1.5 g/dL at 12 months after treatment initiation. In this subgroup, the proportion of patients with Hb &amp;lt;10 g/dL had decreased from 70.0% to 30.1% at 12 months. Fig. 1 shows the Hb levels and proportions of patients with Hb &amp;lt;10 g/dL by treatment type. During the follow-up period, 5,991 (22.5%) deaths, 3,545 (13.3%) CV events, 4,231 (15.9%) dialysis introductions, and 5,561 (20.9%) red-blood-cell transfusions were observed. The risks of clinical events were significantly higher in the low and LAL Hb groups than in the target Hb group (Fig. 2). The hazard ratios (95% CIs) for death, CV events, dialysis introduction, and red-blood-cell transfusion in the low Hb group, compared to the target Hb group were 1.35 (1.20–1.52), 1.90 (1.58–2.27), 1.75 (1.39–2.20), and 2.80 (2.28–3.43), respectively, and in the LAL Hb group were 1.28 (1.14–1.43), 1.71 (1.43–2.04), 1.85 (1.48–2.33), and 1.64 (1.33–2.02), respectively. In HA Hb group, significantly higher risks for dialysis introduction and red-blood-cell transfusion were observed. Conclusion This study reports comprehensive information on anemia management in NDD-CKD patients in clinical practice. Despite treatment for Hb correction, 20–30% of patients persistently remained at low Hb levels. The increased risk of adverse clinical events associated with Hb fluctuations suggest that stable Hb control within the target range is important to reduce the risk of mortality and morbidity in patients with NDD-CKD and anemia.

Ferric Derisomaltose Evaluation in Patients with Non-Dialysis-Dependent Chronic Kidney Disease or Peritoneal Dialysis.

Iron deficiency anemia is common in patients with advanced chronic kidney disease (CKD). Ferric derisomaltose (FDI) enables iron repletion in a single dose, unlike other forms of iron for IV administration, which require multiple doses. Protocols are commonly used with other IV irons, but there are limited Canadian data for FDI, and no protocol exists. To evaluate the efficacy and safety of FDI for patients with CKD and to ascertain information related to its use in Canadian provinces. This retrospective cohort study involved patients with non-dialysis-dependent CKD (NDD-CKD) and patients undergoing peritoneal dialysis (PD) who received FDI in a tertiary hospital in Nova Scotia between June 2020 and May 2021. Each patient was followed for a minimum of 6 months. The efficacy outcomes were the changes from baseline in hemoglobin, transferrin saturation (TSAT), and ferritin after the first dose of FDI and at 3 and 6 months. The safety outcomes were the frequency and types of adverse reactions to FDI. Electronic surveys were sent to 33 Canadian renal pharmacists to gather information about FDI use, dosing, administration, monitoring, funding, and safety in their respective organizations. A total of 52 infusions were administered to 35 patients during the study period. The median times between doses 1 and 2 and between doses 2 and 3 were 19.1 and 6.6 weeks, respectively. The median change from baseline to first post-FDI follow-up blood work was significant for hemoglobin (9.0 g/L, p = 0.023), TSAT (11 percentage points, p < 0.001), and ferritin (271.4 μg/L, p < 0.001). Median darbepoetin doses decreased from baseline to 6 months (p < 0.001). Three adverse reactions occurred. At least 15 (65%) of the 23 survey respondents reported that FDI was funded by their province or was listed on their hospital drug formulary. This study provides evidence that FDI is an effective and safe treatment for anemia in NDD-CKD and PD patients.

Effects of hypoxia-inducible factor-prolyl hydroxylase inhibitors vs. erythropoiesis-stimulating agents on iron metabolism in non-dialysis-dependent anemic patients with CKD: A network meta-analysis.

To compare the effects of five hypoxia-inducible factor-prolyl hydroxylase domain inhibitors (HIF-PHIs), two erythropoiesis-stimulating agents (ESAs), and placebo on iron metabolism in renal anemia patients with non-dialysis-dependent chronic kidney disease (NDD-CKD). Five electronic databases were searched for studies. Randomized controlled clinical trials comparing HIF-PHIs, ESAs, and placebo in NDD-CKD patients were selected. The statistical program used for network meta-analysis was Stata/SE 15.1. The main outcomes were the change in hepcidin and hemoglobin (Hb) levels. The merits of intervention measures were predicted by the surface under the cumulative ranking curve method. Of 1,589 original titles screened, data were extracted from 15 trials (3,228 participants). All HIF-PHIs and ESAs showed greater Hb level-raising ability than placebo. Among them, desidustat demonstrated the highest probability of increasing Hb (95.6%). Hepcidin [mean deviation (MD) = -43.42, 95%CI: -47.08 to -39.76], ferritin (MD= -48.56, 95%CI: -55.21 to -41.96), and transferrin saturation (MD = -4.73, 95%CI: -5.52 to -3.94) were decreased, while transferrin (MD = 0.09, 95%CI: 0.01 to 0.18) and total iron-binding capacity (MD = 6.34, 95%CI: 5.71 to 6.96) was increased in HIF-PHIs versus those in ESAs. In addition, this study observed heterogeneity in the ability of HIF-PHIs to decrease hepcidin. Compared with darbepoetin, only daprodustat (MD = -49.09, 95% CI: -98.13 to -0.05) could significantly reduce hepcidin levels. Meanwhile, daprodustat also showed the highest hepcidin-lowering efficacy (84.0%), while placebo was the lowest (8.2%). For NDD-CKD patients, HIF-PHIs could ameliorate functional iron deficiency by promoting iron transport and utilization, which may be achieved by decreasing hepcidin levels. Interestingly, HIF-PHIs had heterogeneous effects on iron metabolism. https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=242777, Identifier CRD42021242777.

Retrospective Assessment of Total Cost of Care in Non-Dialysis Dependent Chronic Kidney Disease Patients Receiving Parenteral Iron Therapy for Iron Deficiency Anemia

Introduction Iron deficiency anemia (IDA) is a common comorbidity among patients with chronic kidney disease. Iron deficiency occurs in 15% to 48% of non-dialysis dependent chronic kidney disease (ND-CKD) patients with anemia. Parenteral iron therapy is often required in ND-CKD patients with IDA who cannot tolerate or are nonresponsive to oral iron. Available IV iron treatments vary in the amount of iron dose per administration, the number of infusions required to achieve complete iron repletion and drug acquisition cost. The objective of this study was to compare healthcare costs between ferric carboxymaltose (FCM) and low dose IV iron (LDI) for the treatment of IDA in ND-CKD patients. Methods Medical and pharmacy claims from IQVIA PharMetrics® Plus data were analyzed. Adult patients who received first (index) dose of FCM or LDI (i.e., iron sucrose, iron dextran, sodium ferric gluconate complex in sucrose) from 2017 to 2019 were included. Eligible patients were required to be continuously eligible 6 months before (baseline) and 12 months after index IV iron infusion and had medical claims associated with diagnosis of chronic kidney disease (ICD-10: N18.1 to N18.5) and IDA (ICD-10: D50.x) anytime during the 18-month study observation period. In addition, eligible FCM patients were required to receive a second dose of FCM within 21 days of index date. Patients who had claims associated with end stage renal disease (ICD-10: N18.5 and N18.6) or dialysis (HCPCS CPT code: 90935-90999) and patients who had received other IV iron products in the 6-month baseline period were excluded. Unadjusted mean number of IV iron infusions, outpatient visits and hospital admissions in the 6 months before and 12 months following index IV iron dose were summarized on a per-patient-per-month basis. Post-index monthly inpatient, outpatient, and total healthcare costs for FCM and LDI were compared using generalized linear model with gamma log-link adjusting for pre-index monthly cost, age, gender, year of index treatment and the Charlson Comorbidity Index (CCI). Sensitivity analyses comparing FCM versus iron sucrose were performed. Results Data from 3,727 FCM patients [mean (SD) age= 67.9 (13.8) years, 61% females, CCI (SD)=1.9 (2.5)] and 5,068 LDI patients [mean (SD) age=64.8 (15.0) years, 60% females, CCI (SD)=1.6 (2.4)] were analyzed. Within the LDI cohort, 3,489 patients received index iron sucrose treatment [mean (SD) age=64.6 (15.1) years, 60% females, CCI (SD)=1.5(2.4)]. Mean (SD) number of IV iron infusions was 0.24 (0.26) for FCM, 0.43 (0.52) for LDI and 0.46 (0.52) for iron sucrose during the post-index period. During the post-index period, FCM has a smaller increase in the number of outpatient visits (mean change from baseline=0.13) than LDI (mean change from baseline=0.64) and iron sucrose (mean change from baseline=0.70). The number of hospital admissions in the post-index period were numerically lower for FCM (mean change from baseline=-0.05) but numerically higher for LDI (mean change from baseline=0.04) and iron sucrose (mean change from baseline=0.05). Mean total health care cost increased during the 12-month period after IV iron treatment compared to baseline in all treatment groups. After adjusting for pre-index cost and other covariates, FCM treatment was associated with significantly lower post-index inpatient costs [adjusted cost ratio (ACR)= 0.73, p<0.0001], ER costs (ACR=0.76, p<0.0001), outpatient costs (ACR=0.73, p<0.0001) and total costs (including IV iron) (ACR = 0.81, p<0.0001) than LDI. Similar results were observed in the comparisons between FCM and iron sucrose. Conclusion Higher drug acquisition cost of FCM compared to LDI was primarily offset by lower inpatient and outpatient costs during the 12 months after FCM treatment for IDA in ND-CKD patients than LDI, resulting in significantly lower overall total health care cost for FCM compared to LDI. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal

Efficacy and safety of roxadustat for the treatment of anemia in non-dialysis chronic kidney disease patients: A systematic review and meta-analysis of randomized double-blind controlled clinical trials

To evaluate the efficacy and safety of roxadustat in the treatment of anemia in non-dialysis-dependent chronic kidney disease (NDD-CKD) patients. For this systematic review and meta-analysis, we searched for randomized controlled trials (RCTs) of anemia in NDD-CKD patients to assess the efficacy and safety of roxadustat. The primary efficacy endpoint was the proportion of patients who achieved a hemoglobin (Hb) response. Secondary efficacy endpoints were hepcidin, serum iron, serum ferritin (SF), total iron-binding capacity (TIBC), transferrin saturation (TAST), and low-density lipoprotein (LDL). In addition, adverse events (AEs) were compared. Meta-analyses were performed using Revman 5.4 software. The quality of the evidence was assessed using the Cochrane risk of bias tool. This study was conducted under a pre-established protocol registered with PROSPERO (registration number: CRD42021252331). Seven studies enrolled 4,764 patients, of whom 2,730 received roxadustat and 2,034 received placebo. The results of this meta-analysis showed that roxadustat increased Hb levels [weighted mean difference (WMD) = 1.43, 95% CI: 1.17 to 1.68, P < 0.001, I 2 = 95%], and Hb response [relative ratio (RR) = 8.12, 95% CI: 5.80 to 11.37, P < 0.001, I 2 = 61%]. In addition, roxadustat significantly increased transferrin TAST. During the treatment period in patients with anemia, the AEs of roxadustat compared with placebo was not statistically significant. Roxadustat can improve anemia in NDD-CKD patients by increasing Hb levels and regulating iron metabolism, but does not increase the incidence of AEs. [https://www.crd.york.ac.uk/prospero/], identifier [CRD42021252331].

The Influence of Iron-Deficiency Anaemia (IDA) Therapy on Clinical Outcomes and Healthcare Resource Consumptions in Chronic Kidney Disease Patients Affected by IDA: A Real-Word Evidence Study among the Italian Population.

Anaemia is a uraemia-related complication frequently found in non-dialysis-dependent chronic kidney disease (ND-CKD) patients, with iron-deficiency anaemia (IDA) as the main underlying mechanism. Given the suboptimal anaemia management in ND-CKD patients with a co-diagnosis of IDA, this study evaluated the role of IDA therapy on clinical outcomes and healthcare resource consumptions in an Italian clinical setting. A retrospective observational real-world analysis was performed on administrative databases of healthcare entities, covering around 6.9 million health-assisted individuals. From January 2010 to March 2019, ND-CKD patients were included and diagnosed with IDA in the presence of two low-haemoglobin (Hb) measurements. Patients were divided into IDA-treated and untreated, based on the prescription of iron [Anatomical-Therapeutic Chemical (ATC) code B03A] or anti-anaemia preparations (ATC code B03X), and evaluated during a 6-month follow-up from the index date [first low haemoglobin (Hb) detection]. IDA treatment resulted in significantly decreased incidence of all cause-related, cardiovascular-related, and IDA-related hospitalizations (treated vs. untreated: 44.5% vs. 81.8%, 12.3% vs. 25.3%, and 16.2% vs. 26.2%, respectively, p < 0.001). A healthcare direct cost estimation showed that overall mean expenditure per patient reduced by 47% with IDA treatment (5245€ vs. 9918€, p < 0.001), mainly attributable to hospitalizations (3767€ vs. 8486€, p < 0.001). This real-life analysis on Italian ND-CKD-IDA patients indicates that IDA therapy administration provides significant benefits in terms of patients’ clinical outcomes and healthcare cost savings.

Changes in Iron Availability with Roxadustat in Nondialysis- and Dialysis-Dependent Patients with Anemia of CKD.

Roxadustat, a hypoxia-inducible factor prolyl hydroxylase inhibitor, increases hemoglobin by stimulating erythropoietin synthesis and improving iron availability through facilitation of iron uptake and/or release from stores. In this exploratory analysis, we assessed the effect of roxadustat treatment on laboratory parameters related to iron metabolism in patients with anemia of chronic kidney disease (CKD). Data were pooled from pivotal, randomized, phase 3 roxadustat trials: three placebo-controlled, double-blind trials in nondialysis-dependent (NDD) CKD and three open-label, active-comparator (epoetin alfa) trials in dialysis-dependent (DD) CKD. In this exploratory analysis, mean changes from baseline in hemoglobin, iron parameters, and hepcidin, and intravenous (iv) iron use were evaluated. Pooled results in NDD CKD and DD CKD patients are reported. Overall, 4277 patients with NDD CKD and 3890 patients with DD CKD were evaluated. Hemoglobin increases with roxadustat treatment were accompanied by increases in serum iron and total iron-binding capacity (TIBC) and decreases in serum ferritin and hepcidin from baseline through week 52. With epoetin alfa, the hemoglobin increase was accompanied by decreases in serum ferritin and hepcidin, but serum iron decreased, and there was no change in TIBC. With placebo, there were no changes in hemoglobin, iron parameters, or hepcidin. During treatment, iv iron use was reduced with roxadustat versus placebo and epoetin alfa. In patients with NDD CKD and DD CKD, roxadustat treatment is associated with increases in serum iron and TIBC, accompanied by reduced hepcidin and indicative of improved iron kinetics. Patients treated with roxadustat achieved target hemoglobin levels with less iv iron use versus comparators. Practitioners treating patients with anemia of CKD with roxadustat should consider its unique effects when interpreting iron parameters.

Efficacy and safety of vadadustat compared to darbepoetin alfa on anemia in patients with chronic kidney disease: a meta-analysis.

As a novel oral agent in treating anemia of chronic kidney disease (CKD), several clinical trials of vadadustat have been conducted to compare with darbepoetin alfa. This study systematically reviews and investigates the efficacy and safety of vadadustat in the anemia treatment with different duration in both nondialysis-dependent CKD (NDD-CKD) and dialysis-dependent CKD (DD-CKD). Several main databases were searched for randomized controlled trials (RCTs) reporting vadadustat vs darbepoetin alfa for anemia patients with CKD. The outcome indicators were focused on hemoglobin (Hb), the percentage of patients within the target Hb, the need for RBC (Red Blood Cell) transfusions, and serious adverse events (SAEs). Four eligible studies with 8,026 participants were included. The changes of Hb levels from the baseline in the darbepoetin alfa group were significantly higher than that in the vadadustat group with DD-CKD (mean difference (MD) -0.19, [95% confidence interval (CI), -0.21 to -0.17], p < 0.0001). In NDD-CKD patients, the changes of Hb levels in the two groups are not significantly different (MD = -0.06, [95% CI, -0.18 to 0.05], p = 0.006), especially, during the treatment duration of 20-36weeks (MD = 0.02, [95% CI, -0.04 to 0.08], p = 0.51). The percentage of patients within the target Hb was significantly lower in the vadadustat group than that in the darbepoetin alfa group in DD-CKD patients (MD = 0.9, [95% CI, 0.86 to 0.94], p < 0.00001), while in NDD-CKD patients, there was no significant difference (MD = 1.05, [95% CI, 0.99 to 1.12], p < 0.00001). In terms of safety, the two agents had no significant difference in the incidence of RBC transfusions and SAEs (RR = 1.26 [95% CI, 0.99 to 1.61], p = 0.52; RR = 0.97, [95% CI, 0.94 to 1.01], p = 0.19; respectively). Compared to darbepoetin alfa, vadadustat had the same effect in raising the hemoglobin level in NDD-CKD patients in the short term. Vadadustat may become an effective and safe alternative for the treatment of patients with anemia and CKD, especially in NDD-CKD patients. As the application of vadadustat is still under exploration, future research should compensatefor the limitations of our study to estimate the vadadustat's value.

Serum adipocyte fatty acid-binding protein level is positively associated with aortic stiffness in nondialysis chronic kidney disease patients: A cross-sectional study.

Aortic stiffness (AS) is a major predictor of cardiovascular disease and mortality in patients with chronic kidney disease (CKD) and adipocyte fatty acid-binding protein (A-FABP) is a novel adipokine that is positively correlated with AS in the general population. Therefore, we investigated the correlation between serum A-FABP levels and AS in nondialysis CKD patients.Fasting blood samples and baseline characteristics were obtained in 270 patients with nondialysis CKD. Serum A-FABP concentrations were determined by enzyme immunoassay and carotid–femoral pulse wave velocity (cfPWV) measurements were acquired using a validated tonometry system. Patients with cfPWV >10 m/s formed the AS group, while those with values ≤10 m/s comprised the comparison group.Among 270 CKD patients, 92 patients (34.1%) were in the AS group. Compared to those in the comparison group, patients in the AS group were older (P < .001), had a higher prevalence of diabetes, along with higher serum A-FABP level (P < .001), larger waist circumference (P = .004), and lower estimated glomerular filtration rate (P = .001) but higher levels of body fat mass (P = .010), systolic blood pressure (P < .001), fasting glucose (P = .014), blood urea nitrogen (P = .009), and serum creatinine (P = .004). The serum log-A-FABP level was positively associated with log-cfPWV (β = 0.178, P = .001) in nondialysis CKD patients and multivariable logistic regression analysis identified serum A-FABP (P = .006), age (P = .001), and systolic blood pressure (P = .015) as independent predictors of AS in nondialysis-dependent CKD patients.Elevated A-FABP levels may be a significant predictor of AS in nondialysis CKD patients.

Hypoxia inducible factor-prolyl hydroxylase inhibitors in anemic patients with non-dialysis dependent chronic kidney disease: a meta-analysis of randomized clinical trials.

Anemia persists as a challenge in chronic kidney disease (CKD) patients. Current therapies are the injectable erythropoietin stimulating agents (ESA). Concerns have been raised regarding ESA cardiovascular safety, therefore search for an alternative, convenient and safe therapy is underway. Hypoxia inducible factors-prolyl hydroxylase inhibitors (HIF-PHI) are oral agents with promising results. Numerous small studies reported favorable effects with lack of large, powered studies. We conducted a meta-analysis of randomized clinical trials to assess the efficacy and safety of HIF-PHI in non-dialysis-dependent CKD patients. Primary outcome was hemoglobin (Hb) concentration post intervention. Secondary outcomes were all-cause mortality, MACE, and changes in iron metabolism (ferritin, hepcidin). We reported total and serious adverse effects. Data were pooled using a random effect model via RevMan 5.4 software. We identified 7 trials comprising of 8228 patients (mean age 66.5 ± 13.2years, 42% were females, 53% used iron replacement) with a mean follow-up of 52weeks. Compared with the standard of care (ESA), HIF-PHI were non-inferior for treatment of anemia, with comparable effect on mortality and major adverse cardiovascular events. HIF-PHI showed no major safety concerns. Main side effect of HIF-PHI was diarrhea. HIF-PHI might represent a safe, and convenient alternative to ESA in non-dialysis dependent CKD patients with anemia.

MO416: Predicting Serum Bicarbonate in Non-Dialysis Dependent CKD Patients

Abstract BACKGROUND AND AIMS Metabolic acidosis (HCO3 &amp;lt; 22 mmol/L) is associated with an increased hazard of death in patients with chronic kidney disease (CKD) [1, 2]. It is further associated with muscle wasting, bone disease, hypoalbuminemia, increased inflammation, protein malnutrition, and progression of CKD [3]. Hospital Civil de Guadalajara is an urban public hospital serving a population of low socioeconomic status for whom HCO3 measurements are not included in their healthcare services and create costs around 70% of which our population cannot afford. We aimed to develop a model allowing us to predict HCO3 in CKD patients and tested its diagnostic performance. METHOD Patients at CKD stage 3–5 from our pre-dialysis clinic were included in this retrospective, cross-sectional study which served as a model development. Creatinine, weight, height, calcium, phosphorus, sodium, potassium, chloride, urea, presence of diabetes, total body water calculated by the Watson equation and eGFR calculated with the CKD-EPI formula were utilized. We performed uni- and multivariate linear regression between measured serum HCO3 and the available variables. A hypothesis-driven step-wise approach for parameter inclusion based on the Akaike Information criterion and optimization of the coefficient of determination was employed to construct the final model predicting serum HCO3. Diagnostic performance for detecting metabolic acidosis using the estimated HCO3 (eHCO3) was evaluated by receiver operating characteristics curve (ROC) analysis and computation of sensitivity, specificity and the positive and negative predictive values (PPV, NPV). Post-test probabilities at different pre-test probabilities (prevalence) were assessed using Bayes’ theorem. RESULTS We screened 1089 patients and included 284 patients [62 (21 IQR), 56% male, 69±14kg, 27% at CKD stage 3 and 34% and 40% at stage 4 and 5, respectively] in the analysis. The final model [eHCO] = 21.47 + 0.61 Ca + 0.43 Na + 0.95 TBW-0.61 Pi-0.51 K-0.53 Cl-0.008 Urea + 0.95 If diabetic had an adjusted R2:0.57, RMSE 2.4 on 275df, P-value: &amp;lt;0.001. The mean difference between HCO3 and eHCO was 0 (95% CI −4.9 to 4.9). Diagnostic performance quantified as AUC ROC 0.87 (95% CI 0.83–0.91). At a prevalence of metabolic acidosis of 56% with a chosen threshold of 20 mEq/L, the model has a sensitivity of 56% and specificity of 95% and a PPV of 94% and NPV of 63%, at a prevalence of 56%. Simulation of the post-test probabilities using Bayesian analysis is shown in Figure 1. CONCLUSION At a considerably high specificity of 95%, we can make predictions with a relatively low risk of treating subjects without metabolic acidosis with bicarbonate. Given the cost saving for the patients and the added insights and diagnostic capability, we believe that the prediction of serum HCO3 by biochemical parameters as done in our model will prove useful in settings with limited resources such as our uninsured urban population in Mexico. Validation of our model is the next step and planned future research.

Osteosarcopenia in patients with non-dialysis dependent chronic kidney disease

Chronic kidney disease (CKD) is associated with a reduction in bone mineral density (BMD), but less is understood regarding the relation between BMD and muscle mass, especially in non-dialysis dependent-CKD (NDD-CKD). The aim of this study was to explore the prevalence and association of low BMD (osteopenia and osteoporosis) with markers of muscle mass and function in patients with NDD-CKD. This cross-sectional observational study included patients with NDD-CKD. Routine biochemical parameters including those related to mineral and bone metabolism were evaluated. Body composition was assessed by dual energy x-ray absorptiometry (DXA) for BMD (g/cm2), total and trunk body fat (%), total lean soft tissue (LST; kg), and appendicular skeletal muscle mass (ASM; kg) as the sum of the LST from the limbs. The latter two variables were used as markers of muscle mass, together with its height indexed values: ASM/height2 as ASM index (ASMI; kg/m2), and LST/height2 as LST index (LSTI, kg/m2). Muscle quality index (MQI) was calculated as handgrip strength (HGS)/mean ASMarms (kg/kg). Osteosarcopenia was defined according to referenced cut-points for patients presenting with low ASMI, HGS and BMD. Patients (n=257, 57.6% males) had a mean age=64.8±12.9 years, estimated glomerular filtration rate (eGFR)=30.1±12.9ml/min and body mass index (BMI)=26.8±4.8kg/m2. Patients with low BMD (39.4%) presented with lower BMI, LST, LSTI, ASM and ASMI for both sexes. BMD was positively and significantly correlated with LST, LSTI, ASM, ASMI and HGS. Low ASM was associated with low BMD (odds-ratio-OR; 95% confidence interval-CI: males OR=4.54, 2.02-10.21; females OR=4.45, 1.66-11.93). Linear multiple regression analysis (adjusted for sex and eGFR) showed significant associations between T-score with HGS (R2=0.288, R2 adjusted=0.272, standardized coefficient β=0.536, p<0.0001) and also with MQI (R2=0.095, R2 adjusted=0.075, standardized coefficient β=0.309, p=0.024). Osteosarcopenia was present in about 7% of participants and similarly distributed between sexes. Low BMD was prevalent, and associated with low markers of muscle mass and quality, in NDD-CKD patients of both sexes. In view of the known significance of these conditions, targeted interventions are needed to optimize body composition and functional status of these patients.

The efficacy of rehabilitation for elderly chronic kidney disease patients: a retrospective, single-center study.

As the geriatric population is growing rapidly, so is the prevalence of chronic kidney disease (CKD). Suitable rehabilitation programs are needed to decrease disability and improve functionality to maintain independence in activities of daily life. To assess the impact of CKD on the efficacy of rehabilitation in the geriatric population. Retrospective single-center cohort study, demographic and clinical data of 190 elderly, non-dialysis dependent CKD patients, who underwent rehabilitation, during 2016-2020 were analyzed. Early CKD patients had longer duration of rehabilitation as compared with advanced CKD (32.6 ± 19.5 vs. 25.1 ± 17.6days, p = 0.011) and tended to be more independent at discharge (37.2% vs. 27.9%, respectively; p < 0.001). Duration of rehabilitation, Mini-Mental State Examination (MMSE), Functional Independence Measurement (FIM) admission and estimated GFR were important predictors of FIM at discharge. Age was negatively correlated with admission FIM, eGFR, MMSE, and discharge FIM. The odds ratio for mortality among patients with advanced as compared to early CKD was 2.197 (CI 95% 1.159-4.166, p = 0.015). Existing rehabilitation programs raise questions of suitability for the consistently aging population, play an indispensable part in the goal of achieving functional independence in the elderly and should promote further investigation of the efficacy of rehabilitation for CKD patients. Advanced CKD was associated with lower FIM at admission and discharge, shorter duration of rehabilitation and more dependence at discharge, as compared to patients with early CKD. Implementing a multidisciplinary team, focused on the specific needs of geriatric CKD patients, with clear, objective parameters and goals may lead to better rehabilitative outcomes, with decreased public and private costs of ongoing care.

È possibile una gestione “ideale” della pandemia da malattia renale cronica?

Chronic Kidney Disease (CKD) is recognized as one of the major categories of noncommunicable epidemic diseases and in the last decades it has been largely growing in incidence and prevalence all over the world. Ideal management of CKD pandemic should be comprehensive of measures of tertiary, secondary, primary and primordial prevention. So, it should include prompt diagnosis and treatment of traditional and non-traditional risk factors for CKD, optimal conservative treatment for non-dialysis dependent CKD patients and appropriated dialysis therapy or renal transplantation for patients with end-stage renal disease. However, these goals are not easy to obtain on a global scale. It would be possible only by a broad and holistic approach, ranging from good governance to achievement of the sustainable development goals (SDGs).

Frequency and risk factors of frailty in nondialyzable chronic kidney disease geriatric patients

Background Frailty is an additional clinical and economic burden in the setting of chronic kidney disease (CKD). In this study, we aimed to determine the frequency and the risk factors for the occurrence of frailty in nondialyzable CKD geriatric patients' (stages 3–4). Patients and methods We conducted a cross-sectional, analytical study, which included consecutive patients with CKD, who attended the Nephrology Unit of Assiut University Hospital from April 2017 to April 2020. The total number of cases is 77 (21 of the control group and 56 of the patient group). Geriatric patients with aged more than or equal to 60 years and CKD stages 3–4 nondialysis dependent patients were included. The patients will be followed-up for 1 year. Results In terms of the frequency of frailty in geriatric CKD patients, the present study showed that 14.3% of the nondialyzable geriatric CKD patients had frailty. Regarding the predictors of frailty, the present study showed that nondialysis patients with frailty had significantly lower hemoglobin, mean corpuscular volume, mean corpuscular hemoglobin, platelet count, lymphocyte count, monocyte count, higher blood urea, higher serum creatinine, and higher basophil count. Notably, a lower serum magnesium level was noticed in the frail group. Conclusion In conclusion, frailty is not common in geriatric nondialysis dependent CKD patients. Independent risk factors for frailty in CKD include low serum magnesium and high serum creatinine.

Association between Serum Inorganic Phosphorus Levels and Adverse Outcomes in Chronic Kidney Disease: The Fukushima CKD Cohort Study.

Objective Although an association between serum inorganic phosphorus levels and a poor prognosis has been noted in dialysis patients, these associations have been insufficiently reported in non-dialysis-dependent chronic kidney disease (NDD-CKD) patients. This study attempted to determine the association between serum inorganic phosphorus levels and adverse outcomes in Japanese NDD-CKD patients. Methods We investigated the relationships between serum inorganic phosphorus levels and adverse outcomes, such as kidney events, cardiovascular events, and all-cause death, in Japanese NDD-CKD patients using longitudinal data from the Fukushima CKD Cohort Study with a median follow-up period of 2.8 years. The study evaluated 822 patients with NDD-CKD enrolled between June 2012 and July 2014. A kidney event was defined as a combination of doubling of the baseline serum creatinine or end-stage renal disease. Cox regression was performed to analyze the relationships of the quartile of the serum inorganic phosphorus with kidney events, cardiovascular events, and all-cause death. Results The frequency of kidney events per 1,000 person-years exhibited a U-shaped distribution based on serum inorganic phosphorus levels, with these levels not significantly associated with an increased risk of cardiovascular events and all-cause death. A multivariable Cox regression analysis showed an increased risk of kidney events for the highest quartile of the serum inorganic phosphorus levels (≥3.7 mg/dL) versus the second quartile (2.9-3.2 mg/dL, hazard ratio, 3.30; 95% confidence interval, 1.50-7.28; p=0.003). There were no significant associations between the serum calcium levels and adverse outcomes. Conclusion Serum inorganic phosphorus levels were associated with an increased risk of CKD progression in Japanese NDD-CKD patients.

Current status of the assessment of sarcopenia, frailty, physical performance and functional status in chronic kidney disease patients.

Low physical function, frailty, and sarcopenia are common complications of chronic kidney disease (CKD). In this article, we review the epidemiology and pathogenesis of low physical function, as well as its associations with adverse outcomes in CKD patients. Additionally, we present various traditional and novel methods for assessment of physical function in CKD patients. In nondialysis dependent (NDD) and dialysis-dependent CKD patients, the prevalence of low physical function, frailty, and sarcopenia are substantially higher than in the general population. The potential mechanisms of low physical function, frailty, and sarcopenia in CKD patients are due to various factors including underlying kidney disease, co-existing comorbidities, and certain therapeutic interventions utilized in CKD. Increasing evidence has also uncovered the ill effects of impaired physical function on clinical outcomes in CKD patients. Routine assessment of physical function is an under-utilized yet important component in the management of CKD patients. Future studies are needed to determine how prescription of exercise and increased daily physical activity can be tailored to optimize the health and well-being of NDD and dialysis-dependent CKD patients in pursuit of successful aging.