Incidence Of Renal Outcomes Research Articles

Fibroblast growth factor 21 may be a strong biomarker for renal outcomes: a meta-analysis

Background Fibroblast growth factor 21 (FGF21) is deemed to play an important role in kidney outcomes, while the association between FGF21 and various kidney diseases remains largely unclear and inconsistent. Therefore, we conducted this meta-analysis to find out the role of FGF21 in various renal diseases. Methods The outcome indicator of our study was assessed by the pooled standard mean difference (SMD) with 95% confidence intervals (CIs) which were calculated by random-effect model analysis. The risk of bias was assessed by Non-Randomized Studies of Interventions (ROBINS-I) tool. Funnel plot combined with Egger’s and Begg’s tests was performed to estimate the publication bias that existed in the study. Results A total of 28 eligible studies with 19348 participants were included in our research. The agreement between authors reached a kappa-value of 0.88. Overall, the serum FGF21 level was strongly higher in CKD patients (SMD = 0.97 (ng/L); 95% CI, 0.70—1.24 (ng/L)) and the renal outcomes in T2DM patients (SMD = 0.54 (ng/L); 95% CI, 0.39–0.70 (ng/L)) compared with the control group. Consistent with this, the incidence of CKD (OR = 2.56; 95% CI, 1.72–3.81) and the incidence of renal outcomes (OR = 1.63; 95% CI, 1.31–2.01) in T2DM patients was significantly higher in the patients with high FGF21 concentration, indicating that high serum FGF21 level may predict the incidence of CKD and the renal outcomes in T2DM patients. Conclusion Serum FGF21 may be one of the strong predictors for various kidney diseases including the progression of CKD and the hard renal outcomes in type 2 diabetes patients, but more large-scale clinical research are needed to confirm this finding.

Validation of the classification for type 2 diabetes into five subgroups: a report from the ORIGIN trial.

Data analyses from Swedish individuals with newly diagnosed diabetes have suggested that diabetes could be classified into five subtypes that differ with respect to the progression of dysglycaemia and the incidence of diabetes consequences. We assessed this classification in a multiethnic cohort of participants with established and newly diagnosed diabetes, randomly allocated to insulin glargine vs standard care. In total, 7017 participants from the Outcome Reduction with Initial Glargine Intervention (ORIGIN) trial were assigned to the five predefined diabetes subtypes (namely, severe auto-immune diabetes, severe insulin-deficient diabetes, severe insulin-resistant diabetes, mild obesity-related diabetes, mild age-related diabetes) based on the age at diabetes diagnosis, BMI, HbA1c, fasting C-peptide levels and the presence of glutamate decarboxylase antibodies at baseline. Differences between diabetes subtypes in cardiovascular and renal outcomes were investigated using Cox regression models for a median follow-up of 6.2years. We also compared the effect of glargine vs standard care on hyperglycaemia, defined by having a mean post-randomisation HbA1c ≥6.5%, between subtypes. The five diabetes subtypes were replicated in the ORIGIN trial and exhibited similar baseline characteristics in Europeans and Latin Americans, compared with the initially described clusters in the Swedish cohort. We confirmed differences in renal outcomes, with a higher incidence of events in the severe insulin-resistant diabetes subtype compared with the mild age-related diabetes subtype (i.e., chronic kidney disease stage 3A: HR 1.49 [95% CI 1.31, 1.71]; stage 3B: HR 2.25 [1.82, 2.78]; macroalbuminuria: HR 1.56 [1.22, 1.99]). No differences were observed in the incidence of retinopathy and cardiovascular diseases after adjusting for multiple hypothesis testing. Diabetes subtypes also differed in glycaemic response to glargine, with a particular benefit of receiving glargine (vs standard care) in the severe insulin-deficient diabetes subtype compared with the mild age-related diabetes subtype, with a decreased occurrence of hyperglycaemia by 13% (OR 1.36 [1.30, 1.41] on glargine; OR 1.49 [1.43, 1.57] on standard care; p for interaction subtype × intervention = 0.001). Cluster analysis enabled the characterisation of five subtypes of diabetes in a multiethnic cohort. Both the incidence of renal outcomes and the response to insulin varied between diabetes subtypes. These findings reinforce the clinical utility of applying precision medicine to predict comorbidities and treatment responses in individuals with diabetes. ORIGIN trial, ClinicalTrials.gov NCT00069784.

Ambulatory blood pressure monitoring-based analysis of long-term outcomes for kidney disease progression

Non-dipping nocturnal blood pressure (BP) pattern is a predictor of the future decline of renal function; however, it is unclear whether it is still a risk for chronic kidney disease (CKD) patients with normal BP. To solve this question, a retrospective cohort study was conducted, and 1107 CKD patients who underwent ambulatory blood pressure monitoring (ABPM) were enrolled. We divided patients into 4 groups based on their nocturnal BP dipping pattern (dipper or non-dipper) and average 24-hour BP (hypertension or normotension). The cumulative incidence of composite renal outcomes, including a 40% reduction in eGFR, the induction of renal-replacement therapy, or death from renal causes, was analyzed. Overall, 86.1% of participants were non-dippers and 48.2% of them were normotensive. During the median follow-up period of 4.72 years, the incidence of renal composite outcomes was highest in hypertensive non-dipper patients, and was similar between normotensive dipper and non-dipper patients. Multivariate regression analysis revealed that the 24-hour systolic BP, amount of urinary protein, and hemoglobin values were associated with the incidence of renal outcomes. In conclusion, our ABPM-based analysis revealed that a non-dipping BP pattern with normotension does not predict the future incidence of composite renal outcomes in CKD patients.

SUN-291 PREDICTIVE FACTORS OF ESA HYPORESPONSIVENESS IN PRE-DIALYSIS CKD PATIENTS: SECONDARY ANALYSIS OF THE RADIANCE-CKD STUDY

Erythropoiesis-Stimulating Agents [ESA] hyporesponsiveness is related to poor renal outcome in management of renal anemia; however, it is difficult to predict which patients will be hyporesponsive. We previously reported on the RADIANCE-CKD study, a multicenter, open-label, randomized controlled study to evaluate renal outcome by different target hemoglobin [Hb] levels using epoetin beta pegol [CERA] in pre-dialysis CKD patients with poor response to ESA (ASN 2018). The aim of the present study was to predict the patients with ESA hyporesponsiveness among pre-dialysis CKD patients. Pre-dialysis CKD patients (362 patients) with poor response to ESA were randomly assigned to an intensive treatment group (I-group; target Hb level of ≥11 g/dl) or a conservative treatment group (C-group; target Hb level of baseline Hb ±1g/dl). The primary renal composite endpoint was a transition to renal replacement therapy, reduction of eGFR to <6 ml/min/1.73 m2, or >30% reduction of eGFR. In the 3-month landmark analysis, the incidence of renal outcome was evaluated in 3 categories of Hb levels (<10, 10 to <11, ≥11 g/dl) according to tertiles of ESA dose. ESA hyporesponsiveness patients (HYPO) were defined as achieved Hb level <11 g/dl with high tertile and achieved Hb level <10 g/dl with mid-tertile in I-group. The predictive factors of hyporesponsiveness patients were then assessed using a logistic regression model and estimated area under the receiver operating characteristic (ROC) curve. Mean age was 74.7 years and 58.6% of patients were male. Mean baseline eGFR in I-group and C-group were 15.3 and 15.9 ml/min/1.73 m2, respectively. Kaplan-Meier analysis and Cox proportional hazards analysis showed no significant difference in the primary end point between the two groups (99 and 109 events) during the 21-month observation period. In the 3-month landmark analysis, achieved Hb level and required ESA dose were higher in I-group. The incidence of the renal composite endpoint had a tendency to increase in accordance with decrease of Hb levels regardless of the ESA dose in both groups. A total of 30 (54.5%) HYPO patients had the renal composite endpoint, as compared with 54 (50.9%) non-HYPO. Based on the logistic regression analysis, 19 background characteristics (age, BW, eGFR, Alb, ferritin, Hb, CRP, etc.) and 14 biomarkers (IL-6, Hepcidin, TGFβ, CD147, PTH, 25Vitamin-D, etc.) were evaluated as predictive factors of HYPO. The obtained area under the ROC curve (AUC) was 0.88, with sensitivity of 84% and specificity of 84%. Using a branch-and-bound algorithm to find the highest likelihood score statistic for 6 variables, the selected variables were age, Hb, Hepcidin, TGFβ, CD147, and PTH; then, the estimated AUC was 0.82. The patients with ESA hyporesponsiveness among Japanese CKD patients can be predicted based on clinical characteristics and biomarkers in pre-dialysis.

Relationship between changes in body fat and a decline of renal function in the elderly.

Obesity is a risk factor for chronic kidney disease, and its prevalence among the elderly is increasing. We investigated the effects of changes in body fat percentage (BFP) on the longitudinal changes in the estimated glomerular filtration rate (eGFR) in the elderly. This prospective cohort study included 390 participants aged >65 years who underwent bioelectrical impedance analysis at baseline and follow-up as a part of the Korean Longitudinal Study on Health and Aging. After a median follow-up period of 5.3 years, BFP was significantly higher than that at the start point (P<0.05). Participants who had the largest increase in BFP had the highest BMI and waist circumference (WC) (P<0.001). The highest tertile had the highest white blood cell count and erythrocyte sedimentation rate, incidence of rapid progression, and decline in eGFR >25% (P≤0.017, P = 0.025, P = 0.005, respectively). The lowest tertile had the lowest triglyceride and highest high-density lipoprotein levels (P<0.05). The adjusted decline rate in eGFR was correlated with a change in BFP (P = 0.039), but not with that in BMI or WC. The highest tertile had a 4.875-fold increase in the risk for rapid progression to a decline in eGFR (95% CI: 1.366–17.397) and a 4.931-fold decrease in the risk to a decline in eGFR>25% (95% CI: 1.617–15.037), when compared with the lowest tertile. In subgroup analysis, the incidence of renal outcomes was significantly increased according to the increase in BFP in patients with lower eGFR (P≤0.010). A change in BFP may be associated with inflammation and dyslipidemia development, and longitudinal changes in body fat are related to a decrease in eGFR in the elderly.