Obesity-related nephropathy is associated with renal function progression. However, some studies have associated a high body mass index (BMI) with improved renal outcomes—this 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.

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.

Glycated hemoglobin (HbA1c) levels are commonly used to indicate long-term glycemic control. An HbA1c level of 6.5–5.7% is defined as pre-diabetes and is proposed as a criterion for diagnosing metabolic syndrome (MetS). However, HbA1c levels can be affected by chronic kidney disease (CKD). Whether HbA1c is associated with clinical outcomes in nondiabetic CKD patients with or without MetS is still unknown. This study included 1270 nondiabetic CKD stage 1–4 Asian patients, divided by HbA1c and MetS. Through linear regression, HbA1c was positively associated with age, waist circumference, hemoglobin levels, and C-reactive protein and was negatively associated with malnutrition–inflammation. HbA1c levels were 5.5% (0.6%) and 5.7% (0.6%) in non-MetS and MetS, respectively (p < 0.001). In Cox regression, higher-level HbA1c was associated with worse composite renal outcome in MetS patients, but with better renal outcome in non-MetS patients: Hazard ratio (HR) (95% confidence interval [CI]) of HbA1c ≥5.7%, compared with HbA1c <5%, was 2.00 (1.06–3.78) in MetS and 0.25 (0.14–0.45) in non-MetS. An association between HbA1c and all-cause mortality was not found. In conclusion, higher HbA1c levels are associated with worse renal outcomes in nondiabetic CKD stage 1–4 patients modified by the presence of MetS.

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.

Iron deficiency is prevalent in women and patients with chronic kidney disease (CKD). Iron deficiency is not only related to anemia but contributes to adverse consequences for the kidney as well. Whether iron status is associated with renal outcomes after considering sex and anemia in patients with CKD stage 1–4 is unclear. Thus, we investigated the association of iron or iron saturation with renal outcomes in a CKD cohort. During a follow-up of 8.2 years, 781 (31.2%) patients met the composite renal outcome of renal replacement therapy and a 50% decline in renal function. In linear regression, iron was associated with sex, hemoglobin (Hb), and nutritional markers. In a fully adjusted Cox regression model, the male patients with normal iron had a significantly decreased risk of renal outcomes (hazard ratio (HR) 0.718; 95% confidence interval (CI) 0.579 to 0.889), but the female patients did not exhibit this association. The non-anemic patients (Hb ≥ 11 g/dL) had a decreased risk of renal outcomes (HR 0.715; 95% CI 0.568 to 0.898), but the anemic patients did not. In the sensitivity analysis, transferrin saturation (TSAT) showed similar results. When comparing iron and TSAT, both indicators showed similar prognostic values. In conclusion, iron deficiency, indicated by either iron or iron saturation, was associated with poor renal outcomes in the male or non-anemic patients with CKD stage 1–4.