The Prognostic Nutritional Index and Glycemic Status Synergistically Predict Early Renal Function Decline in Type 2...

Background/Objectives: The Prognostic Nutritional Index (PNI), which integrates serum albumin and lymphocyte count, reflects both nutritional and inflammatory status. However, its role in early renal function decline among patients with type 2 diabetes (T2D), particularly in relation to glycemic control, remains unclear. This study aimed to: (1) characterize the dose-response relationship between PNI and early renal function decline in type 2 diabetes using restricted cubic splines; (2) identify whether glycemic control (HbA1c) modifies the PNI-renal decline association; and (3) evaluate the clinical utility of combining PNI and HbA1c for risk stratification. Methods: We analyzed data from 1711 community-based participants with T2D who had preserved renal function at baseline. The PNI was calculated as serum albumin (g/L) + 5 × lymphocyte count (×10⁹/L). The primary outcome was a composite of rapid estimated glomerular filtration rate (eGFR) decline (>3 mL/min/1.73 m² per year) or incident chronic kidney disease (CKD) stage 3. Restricted cubic spline models, multivariable regression, and Johnson-Neyman analyses were used to examine non-linearity and effect modification by glycated hemoglobin (HbA1c). Results: A consistent inverse linear association was observed between PNI and the rate of eGFR decline (P for non-linearity > 0.05). Johnson-Neyman analysis further demonstrated that the protective association of PNI was statistically significant within an HbA1c range of 7.24% to 8.71%. Stratification by clinical cut-offs revealed a significant effect modification by glycemic status. The inverse linear association between PNI and renal risk was most pronounced under hyperglycemic stress, as evidenced by the markedly elevated incidence (50.0%) among individuals with both poor glycemic control (HbA1c ≥ 8%) and low PNI (<50). Conversely, under good glycemic control (HbA1c < 8%), this inverse association was substantially attenuated, with a lower incidence observed in the low-PNI subgroup (6.7%) than in the high-PNI subgroup (15.9%). These findings indicate that the protective role of PNI is conditional upon the glycemic milieu. Conclusions: The PNI demonstrates a stable linear association with early renal function decline in T2D, with its protective effect most pronounced at suboptimal HbA1c levels. Combining PNI and HbA1c effectively identifies a high-risk subgroup characterized by synergistic risk, underscoring the need for integrated nutritional and glycemic management.