High risk of renal outcome of metabolic syndrome independent of diabetes in patients with CKD stage 1-4: The ICKD database.

AIMS: To investigate whether metabolic syndrome (MetS) could predict renal outcome in patients with established chronic kidney disease (CKD). MATERIALS AND METHODS: We enroled 2500 patients with CKD stage 1-4 from the Integrated CKD care programme, Kaohsiung for delaying Dialysis (ICKD) prospective observational study. 66.9% and 49.2% patients had MetS and diabetes (DM), respectively. We accessed three clinical outcomes, including all-cause mortality, RRT, and 50% decline in estimated glomerular filtration rate events. RESULTS: The MetS score was positively associated with proteinuria, inflammation, and nutrition markers. In fully adjusted Cox regression, the hazard ratio (HR) (95% confidence interval) of MetS for composite renal outcome (renal replacement therapy, and 50% decline of renal function) in the DM and non-DM subgroups was 1.56 (1.15-2.12) and 1.31 (1.02-1.70), respectively, while that for all-cause mortality was 1.00 (0.71-1.40) and 1.27 (0.92-1.74). Blood pressure is the most important component of MetS for renal outcomes. In the 2 by 2 matrix, compared with the non-DM/non-MetS group, the DM/MetS group (HR: 1.62 (1.31-2.02)) and the non-DM/MetS group (HR: 1.33 (1.05-1.69)) had higher risks for composite renal outcome, whereas the DM/MetS group had higher risk for all-cause mortality (HR: 1.43 (1.09-1.88)). CONCLUSIONS: MetS could predict renal outcome in patients with CKD stage 1-4 independent of DM.

Non-insulin-based insulin resistance indices for predicting all-cause mortality and renal outcomes in patients with stage 1-4 chronic kidney disease: another paradox.

Non-insulin-based insulin resistance (IR) indices serve as the indicators of metabolic syndrome (MetS) but have limited value for predicting clinical outcomes. Whether the obesity paradox affects the predictive value of these indicators in patients with chronic kidney disease (CKD) remains unknown. We investigated whether MetS and non-insulin-based IR indices can predict all-cause mortality and renal outcomes in a prospective observational study with stage 1-4 CKD Asians (N = 2,457). These IR indices were associated with MetS. A Cox regression model including body mass index (BMI) revealed an association between MetS and renal outcomes. Among the IR indices, only high triglyceride-glucose (TyG) index was associated with adverse renal outcomes: the hazard ratio of Q4 quartile of the TyG index was 1.38 (1.12-1.70). All-cause mortality was marginally associated with MetS but not high IR indices. Low TyG and TyG-BMI indices as well as low BMI and triglyceride were paradoxically associated with increased risks of clinical outcomes. The triglyceride-to-high-density lipoprotein cholesterol ratio and metabolic score for IR indices were not associated with clinical outcomes. In conclusion, MetS and TyG index predict renal outcome and obesity paradox affects the prediction of IR indices in patients with stage 1-4 CKD.

The prognostic value of URR equals that of Kt/V for all-cause mortality in Taiwan after 10-year follow-up.

Kt/V and URR (urea reduction ratio) measurements represent dialysis adequacy. Single-pool Kt/V is theoretically a superior method and is recommended by the Kidney Disease Outcomes Quality Initiative guidelines. However, the prognostic value of URR compared with Kt/V for all-cause mortality is unknown. The effect modifiers and cut-off values of the two parameters have not been compared. We investigated 2615 incident hemodialysis patients with URR of 72% and Kt/V (Daugirdas) of 1.6. The average patient age was 59 years, 50.7% were female, and 1113 (40.2%) died within 10 years. URR and Kt/V were both positively associated with nutrition factors and female sex and negatively associated with body weight and heart failure. In Cox regression mod-els for all-cause mortality, the hazard ratios (HRs) of high URR groups (65-70%, 70-75%, and > 75%) and the URR < 65% group were 0.748 (0.623-0.898), 0.693 (0.578-0.829), and 0.640 (0.519-0.788), respectively. The HRs of high Kt/V groups (Kt/V 1.2-1.4, 1.4-1.7, and > 1.7) and the Kt/V < 1.2 group were 0.711 (0.580-0.873), 0.656 (0.540-0.799), and 0.623 (0.498-0.779), respec-tively. In subgroup analysis, Kt/V was not associated with all-cause mortality in women. The prognostic value of URR for all-cause mortality is as great as that of Kt/V. URR > 70% and Kt/V > 1.4 were associated with a higher survival rate. Kt/V may have weaker prognostic value for women.

Association between Body Mass Index and Renal Outcomes Modified by Chronic Kidney Disease and Anemia: The Obesity Paradox for Renal Outcomes.

Obesity-related nephropathy is associated with renal function progression. However, some studies have associated a high body mass index (BMI) with improved renal outcomes­this is referred to as the obesity paradox for renal outcomes, especially in relation to advanced chronic kidney disease (CKD). Central obesity can explain the obesity paradox in all-cause mortality. However, whether obesity or central obesity is associated with renal outcomes (renal replacement therapy or a 50% decline in the estimated glomerular filtration rate) in patients with advanced CKD remains unclear. Our study included 3605 Asian patients with CKD stages 1−5 divided into six groups according to their BMI (between 15 and 35 kg/m2). Through linear regression, BMI was positively associated with hemoglobin and albumin at CKD stages 4 and 5. In the competing risk Cox regression model, a high BMI (27.5−35 kg/m2) was associated with renal outcomes at CKD stages 1−3, but not stages 4 and 5. A high BMI was associated with renal outcomes in patients with hemoglobin ≥11 g/dL, but not <11 g/dL. A high waist-to-hip ratio was not associated with renal outcomes. We conclude that the CKD stage and anemia may explain the obesity paradox in renal outcomes in patients with CKD.

Hyperuricemia, a Non-Independent Component of Metabolic Syndrome, Only Predicts Renal Outcome in Chronic Kidney Disease Patients without Metabolic Syndrome or Diabetes.

Uric acid (UA) is elevated in metabolic syndrome (MS) and diabetes (DM). UA is associated with central obesity and blood glucose and is proposed as a criterion of MS. Previous reports showed that UA could predict renal outcome in CKD. However, recent clinical trials did not demonstrate the benefits of urate-lowering agents (ULA) for renal outcome. Whether the prognostic value of UA for renal outcome is independent of MS or secondary to MS in CKD patients is unknown. Our study included 2500 CKD stage 1−4 Asian patients divided by UA tertiles and MS/DM. In linear regression, UA was associated with obesity, C-reactive protein, and renal function. In Cox regression, high UA was associated with worse renal outcome in non-MS/DM, but not in MS/DM: hazard ratio (95% confidence interval) of UA tertile 3 was 3.86 (1.87−7.97) in non-MS/DM and 1.00 (0.77−1.30) in MS/DM (p for interaction < 0.05). MS was associated with worse renal outcome, but redefined MS (including hyperuricemia as the 6th criteria) was not. In conclusion, hyperuricemia is associated with worse renal outcome in non-MS/DM and is not an independent component of MS in CKD stage 1−4 patients. Hyperuricemia secondary to MS could not predict renal outcome.

Normal weight and waist obesity indicated by increased total body fat associated with all-cause mortality in stage 3-5 chronic kidney disease.

Patients with chronic kidney disease (CKD) demonstrate a survival benefit with a high body mass index (BMI); this is the obesity paradox. Central obesity has a higher prognostic value than BMI, even in those with normal weight. Whether total body fat percentage (TBF%) provides more information than BMI and waist circumference (WC) remains unknown. We included 3,262 Asian patients with stage 3-5 CKD and divided these patients by TBF% and waist-to-height ratio (WHtR) quartiles (Q1-Q4). TBF% was associated with BMI, WC, nutritional markers, and C-reactive protein. In all patients, BMI but not TBF% or WHtR demonstrated a survival paradox. In patients with BMI <25 kg/m2, but not in those with BMI ≥ 25 kg/m2, TBF% Q4 and WHtR Q4 were associated with all-cause mortality, with hazard ratios [HRs; 95% confidence intervals (CIs)] of 2.35 (1.31-4.22) and 1.38 (1.06-1.80), respectively. The HRs of TBF% Q4 for all-cause mortality were 2.90 (1.50-5.58) in patients with a normal WC and 3.81 (1.93-7.50) in patients with normal weight and normal WC (All P for interaction < 0.05). In conclusion, TBF% can predict all-cause mortality in patients with advanced CKD and a normal weight, normal WC, or both.

U-Shaped Association between Waist-to-Hip Ratio and All-Cause Mortality in Stage 3-5 Chronic Kidney Disease Patients with Body Mass Index Paradox.

The obesity paradox, referring to the association of high body mass index (BMI) with low all-cause mortality risk, is found in patients with chronic kidney disease (CKD). Central obesity is associated with metabolic syndrome and may have better prognostic value than BMI for all-cause mortality. Whether central obesity is associated with all-cause mortality in cases of obesity paradox in CKD patients remains unknown. We included 3262 patients with stage 3-5 CKD, grouped into five quintiles (Q1-5) by waist-to-hip ratio (WHR). Low WHR and BMI were associated with malnutrition and inflammation. In Cox regression, high BMI was not associated with all-cause mortality, but BMI < 22.5 kg/m2 increased the mortality risk. A U-shaped association between central obesity and all-cause mortality was found: WHR Q1, Q4, and Q5 had higher risk for all-cause mortality. The hazard ratio (95% confidence interval) of WHR Q5 and Q1 for all-cause mortality was 1.39 (1.03-1.87) and 1.53 (1.13-2.05) in male and 1.42 (1.02-1.99) and 1.28 (0.88-1.85) in female, respectively. Waist-to-height ratio and conicity index showed similar results. Low WHR or low BMI and high WHR, but not high BMI, are associated with all-cause mortality in advanced CKD.