Non-dialysis Chronic Kidney Disease Research Articles

Association between the intake of plant and animal proteins and the serum fibroblast growth factor-23 level in patients with chronic kidney disease analyzed by the isocaloric substitution model.

Fibroblast growth factor-23 (FGF23) is a phosphaturic hormone secreted by the bone in response to dietary phosphate intake. Since the phosphate content in the diet correlates with the protein content, both plant- and animal-based protein intake can increase the serum FGF23 level. However, a higher percentage of energy from plant protein than from animal protein is associated with a lower serum FGF23 level in patients with chronic kidney disease (CKD) in the United States. Since dietary habits differ between Asian and Western populations, we performed a cross-sectional study to determine the association between the percentages of energy from plant and animal proteins and the serum FGF23 level in Japanese CKD patients. In 107 non-dialysis CKD patients (age: 66 ± 9 years; estimated glomerular filtration rate: 56 ± 21 mL/min/1.73 m2), the percentages of energy from plant and animal proteins were assessed using a food frequency questionnaire based on food groups. Venous blood samples were used to measure the serum FGF23, phosphate, 1,25-dihydroxyvitamin D, and intact parathyroid hormone levels. The percentages of energy from plant and animal proteins showed a negative and positive association, respectively, with the serum FGF23 level. Furthermore, isocaloric substitution modeling showed that replacing animal protein with plant protein was associated with a low serum FGF23 level. Our findings suggest that encouraging diets with high plant protein level may prevent an increase in the serum FGF23 level in Japanese CKD patients.

Physical Frailty and Functional Status in Patients With Advanced Chronic Kidney Disease: A Systematic Review.

With an aging population and growing number of patients with chronic kidney disease (CKD), integrating the latest risk factors when deciding on a treatment plan can result in better patient care. Frailty remains a prevalent syndrome in CKD resulting in adverse health outcomes. However, measures of frailty and functional status remain excluded from clinical decision making. To examine the degree to which different measures of frailty and functional status are associated with mortality, hospitalization, and other clinical outcomes in patients with advanced CKD. Systematic review. Observation studies including cohort study, case-control study, or cross-sectional study examining frailty and functional status on clinical outcomes. There were no restrictions on type of setting or country of origin. Adults with advanced CKD, including both types of dialysis patients. Data including demographic information (e.g., sample size, follow-up time, age, country), assessments of frailty or functional status and their domains, and outcomes including mortality, hospitalization, cardiovascular events, kidney function, and composite outcomes were extracted. A search was conducted using databases Medline, Embase, and Cochrane Central Register for Controlled Trials. Studies were included from inception to March 17, 2021. The eligibility of studies was screened by 2 independent reviewers. Data were presented by instrument and clinical outcome. Point estimates and 95% confidence intervals from the fully adjusted statistical model were reported or calculated from the raw data. A total of 117 unique instruments were found among 140 studies. The median sample size of studies was 319 (interquartile range, 161-893). Most studies focused on incident and chronic dialysis patient populations, with only 15% of studies examining non-dialysis CKD patients. Frailty and lower functional status were associated with an increased risk for adverse clinical outcomes such as mortality and hospitalization. The 5 individual domains of frailty were also found to be associated with poor health outcomes. Meta-analysis could not be performed due to significant heterogeneity between studies and methods used to measure frailty and functional status. Many studies had issues with methodological rigor. Selection bias and the validity of data collection could not be ascertained for some studies. Frailty and functional status measures should be integrated to help guide clinical care decision making for a comprehensive assessment of risk for adverse outcomes among patients with advanced CKD. CRD42016045251.

Nuclear Factor Erythroid 2-Related Factor 2 (Nrf2) and Nuclear Factor-Kappa B (NF- κB) Expression in Chronic Kidney Disease Patients (CKD) from South India

Aim: The present study elucidated the expression level of Nrf2 and NF-κB, in chronic kidney disease (CKD) patients from South India. Further, the expression levels of these genes are analyzed for cytokines TNF-α and IFN-γ and various subgroups of cases including dialysis, non-dialysis, diabetic and non-diabetic CKD patients, and correlation analysis performed. Methods: 133 CKD patients and 133 healthy individuals were enrolled for the evaluation of NF-κB and Nrf2 expression by qPCR. Results: Upregulated Nrf2 mRNA expression (as fold change) was observed in diabetic (Fc: 1.13), and non-diabetic (Fc: 1.30) patients. Inversely, Nrf2 mRNA expression was down regulated in non-dialysis groups (Fc: 0.80). NF-κB expression was significantly upregulated in non-diabetic (Fc:1.92), non-dialysis (Fc:1.59), dialysis (Fc: 1.36) and CKD patients (pooled) (Fc: 1.27). A dysregulated NF-κB expression was observed in diabetic groups (Fc: 0.69). Nrf2 mRNA expression were positively correlated with IFN-γ expression in diabetes (r = 0.28, p = 0.05) and non-diabetic CKD patients (r = 0.37, p < 0.002). Likewise, TNF-α expression was positively correlated with Nrf2 expression in CKD (pooled) patients (r = 0.33, p < 0.000). A negative correlation was observed in Nrf2 and NF-κB expression in CKD (pooled) (r = -0.028, p = 0.833). Conclusion: The study concluded the down regulated Nrf2 and upregulated NF-κB expressions in non-dialysis patients. On the contrary, in diabetic CKD patients, the expression level of NF-κB was downregulated and Nrf2 was upregulated. Thus, a negative correlation was observed between Nrf2 and NF-κB genes with respect to their expression patterns.

Nuclear Factor Erythroid 2-Related Factor 2 (Nrf2) and Nuclear Factor-Kappa B (NF- κB) Expression in Chronic Kidney Disease Patients (CKD) from South India

Aim: The present study elucidated the expression level of Nrf2 and NF-κB, in chronic kidney disease (CKD) patients from South India. Further, the expression levels of these genes are analyzed for cytokines TNF-α and IFN-γ and various subgroups of cases including dialysis, non-dialysis, diabetic and non-diabetic CKD patients, and correlation analysis performed. Methods: 133 CKD patients and 133 healthy individuals were enrolled for the evaluation of NF-κB and Nrf2 expression by qPCR. Results: Upregulated Nrf2 mRNA expression (as fold change) was observed in diabetic (Fc: 1.13), and non-diabetic (Fc: 1.30) patients. Inversely, Nrf2 mRNA expression was down regulated in non-dialysis groups (Fc: 0.80). NF-κB expression was significantly upregulated in non-diabetic (Fc:1.92), non-dialysis (Fc:1.59), dialysis (Fc: 1.36) and CKD patients (pooled) (Fc: 1.27). A dysregulated NF-κB expression was observed in diabetic groups (Fc: 0.69). Nrf2 mRNA expression were positively correlated with IFN-γ expression in diabetes (r = 0.28, p = 0.05) and non-diabetic CKD patients (r = 0.37, p < 0.002). Likewise, TNF-α expression was positively correlated with Nrf2 expression in CKD (pooled) patients (r = 0.33, p < 0.000). A negative correlation was observed in Nrf2 and NF-κB expression in CKD (pooled) (r = -0.028, p = 0.833). Conclusion: The study concluded the down regulated Nrf2 and upregulated NF-κB expressions in non-dialysis patients. On the contrary, in diabetic CKD patients, the expression level of NF-κB was downregulated and Nrf2 was upregulated. Thus, a negative correlation was observed between Nrf2 and NF-κB genes with respect to their expression patterns.

Impact of volume status on sarcopenia in non-dialysis chronic kidney disease patients

There were few data regarding the association of volume status with sarcopenia using muscle mass, strength, and physical performance in non-dialysis chronic kidney disease (ND-CKD) patients. We aimed to evaluate the association between volume status and sarcopenia in ND-CKD patients. Our retrospective study analyzed data from a previous study which included ND-CKD patients who had stable renal function. Our study used its baseline data alone. The edema index and muscle mass were measured using a multi-frequency bioimpedance analysis machine. The edema index was calculated using extracellular water/total body water ratio. The skeletal muscle index (SMI, kg/m2) was calculated using appendicular muscle mass per height squared. Handgrip strength (HGS, kg) was measured during the standing position in all patients. Dynamic gait speed (GS, m/s) was evaluated using 6-m walking speed. Patients with both low muscle mass (SMI < 7.0 kg/m2 for men and < 5.7 kg/m2 for women using bioimpedance analysis) and low HGS (< 28 kg for men and < 18 kg for women) or low GS (< 1.0 m/s) were classified as having sarcopenia. The patients (n = 147) were divided into tertiles based on the edema index level. The mean edema index in the low, middle, and high tertiles was 0.377 ± 0.006, 0.390 ± 0.003, and 0.402 ± 0.006, respectively. The edema index was significantly correlated with SMI, HGS, and GS (r = − 0.343 for SMI, − 0.492 for HGS, and − 0.331 for GS; P < 0.001 for three indicators). The SMI, HGS, and GS values were 8.1 ± 1.0 kg/m2, 33.0 ± 9.4 kg, and 1.2 ± 0.2 m/s in the low tertile,7.8 ± 1.2 kg/m2, 30.0 ± 7.5 kg, and 1.0 ± 0.3 m/s in the middle tertile, and 7.2 ± 1.4 kg/m2, 23.7 ± 7.4 kg, and 1.0 ± 0.3 m/s in the high tertile, respectively. Univariate analyses revealed that SMI was lower in patients in the high tertile than in those in the low tertile. HGS was lowest in high tertile, and GS was greatest in the low tertile. The high tertile for predicting sarcopenia had an odds ratio of 6.03 (95% CI, 1.78–20.37; P = 0.004) compared to low or middle tertiles. The results of multivariate analyses were similar to those of the univariate analyses. The subgroup analyses showed that statistical significance was greater in < 65 years and men than ≥ 65 years and women. The present study showed that the edema index is inversely associated with sarcopenia, muscle mass index, strength, and physical performance in ND-CKD patients. However, considering the limitations of our study such as its small sample size, this association was not strong. Further studies that include volume-independent measurements, data on physical activity and diet, and a larger number of patients are warranted to overcome these limitations.

Relationships between Sclerostin, Leptin and Metabolic Parameters in Non-Dialysis Chronic Kidney Disease Males.

Sclerostin is an inhibitor of the Wnt-beta-catenin pathway. The relationship between sclerostin and adipose tissue or between sclerostin and nutritional status has been the subject of research interest in the last decade. Sclerostin concentrations are elevated in patients with chronic kidney disease (CKD). Leptin is an adipocytokine which inhibits food intake by stimulating the satiety center in the hypothalamus. Leptin concentrations rise with the reduction of eGFR (glomerular filtration rate). The aim of this study was to investigate the possible association between sclerostin and leptin, between sclerostin and selected poor prognostic factors of CKD progression, and between sclerostin and nutritional parameters in non-dialysis CKD male patients. 101 men with non-dialysis CKD stage 3-5 were included in the study. Bioimpedance spectroscopy (BIS) was used to measure body composition. Blood samples were drawn to measure the serum concentrations of sclerostin, leptin, creatinine, hemoglobin (Hgb), parathormone (PTH), inflammatory markers, and markers of nutritional status. We also measured homeostatic model assessment of insulin resistance (HOMA-IR) as well as blood pressure. We observed a significant, positive relationship between sclerostin and age, leptin, and glycated hemoglobin (HgbA1c) concentrations. A significant, negative association was observed between sclerostin and eGFR. Sclerostin is associated with leptin in non-dialysis CKD male patients. Sclerostin is also related to metabolic disturbances such as hyperglycemia in this population.

Antidyslipidemia Pharmacotherapy in Chronic Kidney Disease: A Systematic Review and Bayesian Network Meta-Analysis

The benefits and safety of antidyslipidemia pharmacotherapy in patients with chronic kidney disease were not well defined so the latest evidence was summarized by this work. This systematic review and Bayesian network meta-analysis (NMA) included searches of PubMed, Embase, and Cochrane Library from inception to 28 February 2022, for randomized controlled trials of any antilipidaemic medications administered to adults with chronic kidney disease [CKD: defined as estimated glomerular filtration rate (eGFR) ≤ 60 mL/min/1.73 m2 not undergoing transplantation], using the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) tool to assess the certainty of the evidence. 55 trials and 30 works of them were included in our systematic review and NMA, respectively. In comparisons with no antidyslipidemia therapy or placebo, proprotein convertase subtilisin/Kexin type 9 inhibitors plus statin (PS) was the most effective drug regimen for reducing all-cause mortality (OR 0.62, 95% CI [0.40, 0.93]; GRADE: moderate), followed by moderate-high intensity statin (HS, OR 0.76, 95% CI [0.60, 0.93]; I2 = 66.9%; GRADE: moderate). PS, HS, low-moderate statin (LS), ezetimibe plus statin (ES), and fibrates (F) significantly decreased the composite cardiovascular events. The subgroup analysis revealed the null effect of statins on death (OR 0.92, 95% CI [0.81, 1.04]) and composite cardiovascular events (OR 0.94, 95% CI [0.82, 1.07]) in dialysis patients. In nondialysis CKD patients, statin-based therapies could significantly and safely reduce all-cause death and major composite cardiovascular events despite the presence of arteriosclerotic cardiovascular disease and LDL-c levels. Aggressive medication regimens, PS and HS, appeared to be more effective, especially in patients with established CAD.

Efficacy and Safety of Sevelamer Carbonate in Chinese Nondialysis Chronic Kidney Disease Patients with Hyperphosphatemia: A Randomized, Double-Blind, Parallel-Group Study

Introduction: Previous studies suggested that sevelamer carbonate is well tolerated with a favorable efficacy and safety profile in both dialysis and nondialysis patients in Europe; however, the efficacy remains controversial, and few studies have examined sevelamer carbonate therapy in other ethnic nondialysis CKD patients. This study assessed the efficacy and safety of sevelamer carbonate in Chinese nondialysis CKD patients with hyperphosphatemia. Methods: The multicenter, randomized, double-blind, parallel-group, placebo-controlled, and phase 3 clinical trial enrolled 202 Chinese nondialysis CKD patients with serum phosphorus ≥1.78 mmol/L. Patients were randomly assigned 1:1 to receive sevelamer carbonate (2.4–12 g per day) or placebo for 8 weeks. The primary outcome was the change in serum phosphorous between baseline and week 8. Results: Totally 482 Chinese patients were screened and 202 were randomized (sevelamer carbonate, n = 101; placebo, n = 101). The mean serum phosphorous decreased significantly in patients treated with sevelamer carbonate compared with placebo (−0.22 ± 0.47 vs. 0.05 ± 0.44 mmol/L, p < 0.0001). Significantly (p < 0.0001), decreases of serum total cholesterol, low-density lipoprotein cholesterol, and calcium-phosphorus (Ca × P) product levels from baseline to week 8 were shown in sevelamer carbonate group compared with placebo group. Serum intact parathyroid hormone was not significantly changed in the sevelamer carbonate group (p = 0.83). Patients in the sevelamer carbonate group experienced similar adverse events as the placebo group. Conclusion: Sevelamer carbonate is an effective and well-tolerated phosphate binder in advanced nondialysis CKD Chinese patients with hyperphosphatemia.

Gout among Patients with Dialysis: Prevalence, Associated Factors, Treatment Patterns, and Outcomes-Population-Based Retrospective Cohort Study.

Key Points Population-based retrospective cohort study to evaluate clinical correlates of gout and its impact on patients undergoing chronic dialysis.13.5% of US dialysis-dependent patients had gout and were older and male, with a higher prevalence of hypertension and cardiovascular disease.Gout diagnosis was associated with a higher incidence of cardiovascular conditions, levels of anemia, hospitalization, and mortality. Background An association between gout and nondialysis chronic renal disease has long been recognized, yet limited research exists regarding prevalence, treatment, anemia management, and outcomes in patients with ESKD undergoing dialysis. Methods Using data from United States Renal Data System, we conducted a population-based retrospective cohort study in adult patients covered by Medicare and on dialysis in 2017. Multivariate logistic regression models were used to estimate potential factors and odds of gout diagnosis. Antigout medications and impact on anemia management were assessed and compared between gout and nongout dialysis patients using descriptive and regression analyses. Associations for all-cause mortality and cardiovascular-related hospitalizations during 1 year of study follow-up were compared between gout and nongout patients using multivariate Cox regression models. Results Of 231,841 ESKD Medicare patients in 2017 undergoing continuous dialysis, 31,300 (13.5%) had one or more gout diagnostic code(s). Increased odds of having a gout diagnosis were independently associated with older age, male sex, Asian race, obesity, hypertension, and cardiovascular disease. Gout diagnosis was associated with higher prevalence for anemia as indicated by increased erythropoietin-stimulating agent requirements (odds ratio=1.18 for high versus low erythropoietin-stimulating agent dose, 95% confidence interval [95% CI], 1.14 to 1.22) and likelihood of blood transfusions (odds ratio=1.34, 95% CI, 1.30 to 1.38). During the 1-year study follow-up, mortality among gout versus nongout patients was higher by 3% (95% CI, 0 to 6) and a composite association of mortality and cardiovascular disease hospitalization was higher by 6% (95% CI, 3 to 9) after adjusting for comorbid conditions. Conclusions A gout diagnosis was found in 13.5% of US dialysis-dependent patients and was associated with a higher burden of comorbid cardiovascular conditions as well as an elevated incidence of hospitalization and mortality. These observations improve our current understanding of gout among the dialysis population and highlight the importance of new and better treatments to improve outcomes.

Uric Acid, Ferritin, Albumin, Parathyroid Hormone and Gamma-Glutamyl Transferase Concentrations are Associated with Uremic Cardiomyopathy Characteristics in Non-Dialysis and Dialysis Chronic Kidney Disease Patients.

Circulating uric acid, ferritin, albumin, intact parathyroid hormone and gamma-glutamyl transferase each participate in biochemical reactions that reduce or/and enhance oxidative stress, which is considered the final common pathway through which pathophysiological mechanisms cause uremic cardiomyopathy. We hypothesized that the respective biomarkers may be involved in the development of uremic cardiomyopathy characteristics and can be useful in their identification among chronic kidney disease patients. We assessed traditional and non-traditional cardiovascular risk factors including biomarker concentrations and determined central systolic blood pressure using SphygmoCor software and cardiac structure and function by echocardiography in 109 (64 non-dialysis and 45 dialysis) patients. Associations were evaluated in multivariate regression models and receiver operator characteristic (ROC) curve analysis. Each biomarker concentration was associated with left ventricular mass beyond stroke work and/or inappropriate left ventricular mass in all, non-dialysis and/or dialysis patients. Ferritin, albumin and gamma-glutamyl transferase levels were additionally associated with E/e' in all, non-dialysis and/or dialysis patients. Dialysis status influenced the relationship of uric acid concentrations with inappropriate left ventricular mass and those of gamma-glutamyl transferase levels with left ventricular mass and inappropriate left ventricular mass. In stratified analysis, low uric acid levels were related to inappropriate left ventricular mass in dialysis but not non-dialysis patients (interaction p=0.001) whereas gamma-glutamyl transferase concentrations were associated with left ventricular mass and inappropriate left ventricular mass in non-dialysis but not dialysis patients (interaction p=0.020 to 0.036). In ROC curve analysis, uric acid (area under the curve (AUC)=0.877), ferritin (AUC=0.703) and albumin (AUC=0.728) concentrations effectively discriminated between dialysis patients with and without inappropriate left ventricular hypertrophy, left ventricular hypertrophy, and increased E/e,' respectively. Uric acid, ferritin, albumin, parathyroid hormone and gamma-glutamyl transferase were associated with uremic cardiomyopathy characteristics and could be useful in their identification. Our findings merit validation in future longitudinal studies.

Prevalence, Risk Factors and Impact of Proteinuria-Associated Hypomagnesemia in Chronic Kidney Disease Patients: A Cross Sectional Study

Background and Aim: Chronic kidney disease (CKD) patients who have hypomagnesemia are at greater risk of mortality and progression. A limited amount of data is available on the prevalence of hypomagnesemia in kidney-related risk factors and chronic kidney disease patients. The present study aimed to assess the Proteinuria-associated hypomagnesemia in chronic renal disease patients: prevalence, risk factors, and effect. Patients and Method: This cross-sectional study was carried out on 128 chronic kidney disease patients in the Medicine Department of Shifa International Hospital, Rawalpindi from January 2022 to August 2022. Patients were categorized into two groups based on estimated glomerular filtration rate (eGFR) are as follows: group-I composed of Proteinuric and group-II non-proteinuric. Prior to study conduction, the ethical committee approved the protocol. Patients with prior history of ileostomy, malignancy, chronic diarrhea, colostomy, and using magnesium based medications were excluded. Detailed history, physical examination, and investigations such as serum total magnesium level (mg/dl), serum sodium level (mg/dl), serum creatinine (mg/dl), and total cholesterol and triglycerides (mg/dl) were recorded. Hypomagnesemia was defined as a serum magnesium level &lt; 1.8 mg/dL. Results: Of the total 128 CKD patients, there were 66 (51.6%) male and 62 (48.4%) females. Group I and II had 64 patients each. The overall mean age of group-I and group-II was 48.82±12.52 and 48.21±10.64 years respectively. The prevalence of hypomagnesemia (&lt;1.8 mg/dL) in the proteinuric group was 20 (31.3%). Diabetic patients are more susceptible to hypomagnesemia. The incidence of diabetic, hypertensive, and both diabetic and hypertensive was 12 (60%), 3 (15%), and 5 (25%) respectively among 20 hypomagnesemia. Hypomagnesemia patients had higher CRP (46 mg/L), UACR (2064 mg/g), lower serum potassium (56.4%), lower mean hemoglobin levels (10.2 g/dL), and lower serum sodium (34.9%) as compared to normomagnesemic patients 12 mg/L, 810 mg/g, 24.8%, 11.25 g/dL, and 8.6% respectively. Conclusion: The present study found that there is an independent association between hypomagnesemia and proteinuria in non-dialysis CKD patients. Anemia and hyperparathyroidism are risk factors for inflammation and anemia in CKD patients pre-dialysis. Dietary magnesium supplementation and hypomagnesemia correction may retard proteinuria and CKD progression in CKD patients. Keywords: Chronic kidney disease, Proteinuria-associated hypomagnesemia, Risk factors

Nutritional Adequacy of Essential Nutrients in Low Protein Animal-Based and Plant-Based Diets in the United States for Chronic Kidney Disease Patients

The nutritional adequacy of both animal-based and plant-based low protein diets (LPDs) and moderate protein diets that are recommended for patients with chronic kidney disease have not been well examined. We therefore analyzed the nutrient content of three representative LPDs and moderate protein diets (lacto-ovo vegetarian, omnivorous, and vegan) containing foods that are likely to be prescribed for nondialyzed chronic kidney disease or chronic dialysis patients in the United States to determine the nutritional adequacy at different levels of protein intake. Theoretical 3-day menus were developed as per current renal dietary guidelines to model each diet at 7 different levels of protein intake (0.5-1.2g/kilograms body weight/day [g/kg/d]). The diets were analyzed for their content of essential amino acids (EAAs) and other essential nutrients. At an a priori recognized inadequate dietary protein level of 0.5g/kg/d, all 3 diets failed to meet the Recommended Dietary Allowances (RDAs) for the following EAAs: histidine, leucine, lysine, and threonine. The omnivorous LPD met both the RDA and Estimated Average Requirement at levels of 0.6g protein/kg/d or more. The lacto-ovo and vegan diets at 0.6 and 0.8g protein/kg/d, respectively, were below the RDA for lysine. The amounts of several other vitamins and minerals were not uncommonly reduced below the RDA or Adequate Intake with all 3 LPDs. In comparison to omnivorous LPDs, both vegan and lacto-ovo LPDs are more likely to be deficient in several EAAs and other essential nutrients. To provide sufficient amounts of all EAA, vegan and lacto-ovo LPDs must be carefully planned to include adequate amounts of appropriate dietary sources. Supplements of some other essential nutrients may be necessary with all three LPDs.

Serum triglycerides level is independently associated with renal outcomes in patients with non-dialysis chronic kidney disease: Results from KNOW-CKD study.

To investigate whether high serum triglycerides (TG) level is associated with adverse renal outcomes in patients with non-dialysis chronic kidney disease (CKD), a total of 2,158 subjects from a prospective cohort study (Korean Cohort Study for Outcome in Patients With Chronic Kidney Disease) were divided into the quartile by serum TG level. The primary outcomes were composite renal events, which is defined as a composite of decline of kidney function (the first occurrence of > 50% decline of estimated glomerular filtration rate or doubling of serum creatinine from the baseline) or onset of end-stage renal disease (initiation of dialysis or kidney transplantation). During the median follow-up of 6.940 years, the cumulative incidence of composite renal event was significantly differed by serum TG level in Kaplan-Meier curve analysis (P < 0.001, by Log-rank test). Cox regression analysis demonstrated that, compared to that of the 1st quartile, the risk of composite renal event was significantly higher in the 4th quartile (adjusted hazard ratio 1.433, 95% confidence interval 1.046 to 1.964). The association between high serum TG level and adverse renal outcome remained consistent in the cause-specific hazard model. Subgroup analyses revealed that the association is modified by age, estimated glomerular filtration rate, and spot urine albumin-to-creatinine ratio. In conclusion, high serum TG level is independently associated with adverse renal outcomes in patients with non-dialysis CKD. Interventional studies are warranted to determine whether lowering serum TG levels may alter the natural course of CKD.

Prise en charge de la carence martiale au cours de la maladie rénale chronique : mise au point et proposition d’un algorithme

Iron deficiency is very common in chronic kidney disease, even before the dialysis stage. It is an independent factor of morbidity and mortality in patients with non-dialysis chronic kidney disease. During chronic kidney disease, iron deficiency is defined by a transferrin saturation <20% and/or a serum ferritin <100 μg/L. In France, about half of non-dialysis chronic kidney disease patients have absolute iron deficiency (transferrin saturation <20% and serum ferritin <100 μg/L) and/or functional iron deficiency (transferrin saturation <20% and serum ferritin >100 μg/L). Despite this, iron deficiency is usually not investigated. In fact, more than 60% of nephrologists do not assess iron status at least once a year. In addition, iron deficiency is rarely treated: only 12% of patients are prescribed oral or intravenous iron. Early detection and treatment are fundamental and should be systematic. In order to help improve the management of iron deficiency among non-dialysis chronic kidney disease patients, we propose an algorithm that takes into account current recommendations and the most recent data from the literature. Initial blood test requires the measurement of hemoglobin concentration, transferrin saturation and serum ferritin. A transferrin saturation <20% establishes the diagnosis of iron deficiency and the serum ferritin level points towards an absolute or functional deficiency. The combination of both values makes it possible to adapt the treatment, particularly in an inflammatory context where oral iron is not effective.

Periodic limb movements among dialysis and non-dialysis chronic kidney disease patients: a comparative study

BackgroundPeriodic leg movement disorder is defined as periodic episodes of repetitive limb movements during sleep that mainly occurs in the lower limb, including the hips, knees, and toes, and sometimes affects the upper limb. It may be accompanied by frequent nocturnal arousals, and if so, this sleep disturbance may cause excessive daytime sleepiness. Chronic kidney disease patients are at risk of periodic leg movements and common causes are iron deficiency, anemia, raised serum calcium, and central and peripheral nervous system disorders. This study aimed to screen the prevalence of periodic limb movements among chronic kidney disease patients using full-night attended polysomnography, compare dialysis with non-dialysis CKD patients, and correlate PLM prevalence with the HGB level and degree of renal impairment.ResultsThis cross-sectional study was carried out on one hundred chronic kidney disease patients during the period between May 2017 and March 2020. The patients were subdivided into two groups: group I included patients on regular hemodialysis (n = 50), and group II included patients not on dialysis. All patients were screened for periodic limb movement using full-night attended polysomnography. Our study revealed a high prevalence of periodic limb movements in both groups of chronic kidney disease patients (60% in dialysis and 66% in non-dialysis patients) with mean PLM indices insignificantly higher in group I than group II (29.90 ± 19.19/h vs. 17.54 ± 13.56/h, P-value = 0.748). Moreover, there was a significant positive correlation between periodic leg movements and serum urea level (r-value = 0.38 and 0.33 and P-value = 0.04 and 0.030 in group I and group II consequently). Also, we reported a significant negative correlation between periodic leg movements and hemoglobin level (r = −0.251 and −0.291 and P-value = 0.037 and 0.010 in group I and group II consequently).ConclusionPeriodic leg movement disorder is highly prevalent among CKD patients either on dialysis or not, and good management of renal dysfunction and anemia in those patients can help in the management of PLM.

Correlation between Degree of HT with Degree of Albuminuria in Non-dialysis Chronic Kidney Disease Patients at Hypertension Kidney Polyclinic Dr. Soetomo General Hospital

Background: Hypertension (HT) in chronic kidney disease (CKD) occurs through increased activity Renin Angiotensin Aldosterone System (RAAS). According ISH 2020, degree of HT is divided into grade 1 and 2. Uncontrolled HT cause damage glomerular capillaries, thereby affecting presence of albuminuria. According KDIGO 2013, degree of albuminuria is divided into mild, moderate, and severe. Albuminuria that lasts more than 3 months indicates CKD. Until now, research on correlation between degree of HT with degree of albuminuria is still limited. This study aims to determine correlation between degree of HT with degree of albuminuria in non-dialysis CKD patients at Hypertension Kidney Polyclinic Dr. Soetomo General Hospital. Methods: Analytical observational study with cross sectional design using medical records of non-dialysis CKD patients at Hypertension Kidney Polyclinic Dr. Soetomo General Hospital for period of May-October 2021, according to inclusion and exclusion criteria. Correlation test using spearman test. Results: There were 75 study subjects with male (61.3%), age 46-65 years old (42.7%), comorbidities other than HT were DM (32%), HT duration <5 years (58.7% ), controlled HT (66.7%), taking 1 anti-HT (74.7%), ARB (26.7%), severe albuminuria (50.7%). This study showed no correlation between degree of HT with degree of albuminuria (p-value=0.982). Conclusion: There is no correlation between degree of HT with degree of albuminuria in non-dialysis CKD patients at Hypertension Kidney Polyclinic Dr. Soetomo General Hospital.

Use of Hypoxia-Inducible Factor Prolyl Hydroxylase Inhibitor Agents for Anemia in Non-Dialysis-Dependent Chronic Kidney Disease: A Systematic Review and Meta-Analysis

Background: Anemia is a common complication associated with chronic kidney disease (CKD), driven by decreased erythropoietin (EPO) production and dysregulated iron metabolism. Anemia is associated with decreased quality of life, as well as increased cardiovascular events, dialysis requirements, and mortality. Treatment classically consists of iron repletion and erythropoietin stimulating agents (ESA). However, use of these agents can be associated with hyporesponsiveness, a need for close monitoring to avoid adverse cardiovascular events, and patient inconvenience due to subcutaneous or intravenous administration. Hypoxia-inducible factor prolyl hydroxylase inhibitors (HIF-PHIs) are novel oral therapeutic agents that promote accumulation of HIF transcription factors and expression of HIF-responsive genes, leading to increased synthesis of EPO and proteins involved in iron metabolism. Multiple large randomized controlled trials (RCTs) investigating the safety and efficacy of HIF-PHIs in the treatment of anemia of non-dialysis dependent CKD (NDD-CKD) have been completed. However, to the best of our knowledge, there have been no recent comprehensive systematic reviews synthesizing this evidence. Aim: The objective of this systematic review is to assess the safety and efficacy of HIF-PHIs in the treatment of anemia caused by NDD-CKD. Methods: A comprehensive search of MEDLINE, Embase, Cochrane (CENTRAL), and the grey literature was done from inception to April 2022. Studies were screened at abstract and full-text level independently and in duplicate. English-language phase three RCTs investigating the use of HIF-PHIs versus placebo or ESAs in anemia of NDD-CKD were included. Baseline characteristics, intervention details, comparator details, and outcome measurement timing were collected. Our primary efficacy outcome measures were mean change in hemoglobin from baseline and proportion of patients achieving a hemoglobin response. Our primary safety outcome was major adverse cardiac events (MACE) defined as a composite of nonfatal myocardial infarction, nonfatal stroke, and all-cause mortality. Meta-analysis was done using DerSimonian and Laird random effects model and reported as relative risks (RR) or mean differences (MD) with 95% confidence intervals (CI). Results: 14 studies with a total of 12,681 patients were included in the analysis. HIF-PHIs were associated with increased hemoglobin response rate compared to placebo (RR 9.02, 95%CI 6.85,11.86, p<0.005; I2=56%, N=5). There was no significant difference in hemoglobin response rate for HIF-PHIs versus ESAs (RR 0.97, 95%CI 0.9,1.04, p=0.36; I2=76%, N=9). HIF-PHIs were associated with an increased change in hemoglobin from baseline compared to placebo (MD=1.57, 95%CI 1.29,1.85, p<0.05; I2=93%, N=4). There was no significant difference in mean change in hemoglobin from baseline between HIF-PHIs and ESAs (MD -0.06, 95%CI -0.19,0.07, p=0.38; I2=0, N=2). There was no statistically significant difference in MACE between HIF-PHI and placebo (RR 1.14, 95%CI 0.93,1.40, p=0.2; I2=11%, N=4) or ESA (RR 1.03, 95%CI 0.89, 1.19, p=0.70; I2=23%, N=9). Conclusion: HIF-PHIs are associated with increased mean change in hemoglobin and hemoglobin response rate compared to placebo. HIF-PHIs are non-inferior to ESAs for these outcomes. When used to current hemoglobin targets, MACE outcomes are similar to those seen with ESAs.

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

The Codevelopment of "My Kidneys & Me": A Digital Self-management Program for People With Chronic Kidney Disease.

Health care self-management is important for people living with nondialysis chronic kidney disease (CKD). However, the few available resources are of variable quality. This work describes the systematic codevelopment of "My Kidneys & Me" (MK&M), a theory-driven and evidence-based digital self-management resource for people with nondialysis CKD, guided by an established process used for the successful development of the diabetes education program MyDESMOND (Diabetes Education and Self-Management for Ongoing and Newly Diagnosed, DESMOND). A multidisciplinary steering group comprising kidney health care professionals and researchers and specialists in the development of complex interventions and digital health provided expertise in the clinical and psychosocial aspects of CKD, self-management, digital health, and behavior change. A patient and public involvement group helped identify the needs and priorities of MK&M and co-design the resource. MK&M was developed in 2 sequential phases. Phase 1 involved the codevelopment process of the MK&M resource (content and materials), using Intervention Mapping (IM) as a framework. The first 4 IM steps guided the development process: needs assessment was conducted to describe the context of the intervention; intervention outcomes, performance objectives, and behavioral determinants were identified; theory- and evidence-based change methods and practical strategies to deliver change methods were selected; and program components were developed and refined. Phase 2 involved the adoption and adaptation of the existing MyDESMOND digital platform to suit the MK&M resource. The needs assessment identified that individuals with CKD have multiple differing needs and that delivering a self-management program digitally would enable accessible, tailored, and interactive information and support. The intended outcomes of MK&M were to improve and maintain effective self-management behaviors, including physical activity and lifestyle, improve knowledge, promote self-care skills, increase self-efficacy, and enhance well-being. This was achieved through the provision of content and materials designed to increase CKD knowledge and patient activation, reduce health risks, manage symptoms, and improve physical function. Theories and behavior change techniques selected include Self-Management Framework, Capability, Opportunity, Motivation Behavior model components of Behaviour Change Wheel and taxonomy of behavior change techniques, Health Action Process Approach Model, Common Sense Model, and Social Cognitive Theory. The program components developed comprised educational and behavior change sessions, health trackers (eg, monitoring blood pressure, symptoms, and exercise), goal-setting features, and forums for social support. The MyDESMOND digital platform represented an ideal existing platform to host MK&M; thus, the MyDESMOND interface and features were adopted and adapted for MK&M. Applying the IM framework enabled the systematic application of theory, empirical evidence, and practical perspectives in the codevelopment of MK&M content and materials. Adopting and adapting a preexisting platform provided a cost- and time-efficient approach for developing our digital intervention. In the next stage of work, the efficacy of MK&M in increasing patient activation will be tested in a randomized controlled trial.

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.