**Background:** Chronic kidney disease (CKD) affects approximately 10% of the global population and is associated with high morbidity, mortality, and healthcare costs. While lower handgrip strength and slower walking pace have been linked to poor outcomes in patients with established CKD, their relationship with the development of incident CKD in the general population was uncertain. This study aimed to investigate the individual and combined associations of handgrip strength and walking pace with incident CKD using data from the UK Biobank.
**Methods:** The analysis included 417,504 UK Biobank participants (mean age 56.3 years, SD 8.1; 46.0% male) who were free of kidney disease at baseline (no self-reported CKD, eGFRcr ≥60 mL/min/1.73 m², and ACR <30 mg/g). Handgrip strength was measured using a Jamar hydraulic hand dynamometer, with the mean of right and left values used. Sex-specific quartiles were defined: Q1 (F: <19.5 kg; M: <34.0 kg), Q2 (F: 19.5–<23.5 kg; M: 34.0–<40.0 kg), Q3 (F: 23.5–<28.0 kg; M: 40.0–<45.5 kg), Q4 (F: ≥28.0 kg; M: ≥45.5 kg). Walking pace was self-reported as slow (7.3%), average (52.7%), or brisk (40.0%). Incident CKD was identified through linkage to health records using ICD-9/ICD-10 codes and OPCS-4 procedure codes. Cox proportional hazards models were used, with progressive adjustment for demographics, lifestyle factors, and laboratory values (Model 3). Median follow-up was 12.1 years (IQR 11.3–12.8).
**Key Results:** Over follow-up, 11,064 participants (2.7%) developed incident CKD. Handgrip strength showed a significant inverse dose-response relationship with CKD risk in both sexes (both P for trend <0.001). Compared with the lowest quartile (Q1), adjusted HRs (95% CI) for Q2, Q3, and Q4 were 0.84 (0.79–0.89), 0.76 (0.71–0.81), and 0.72 (0.67–0.77), respectively (Model 3). For walking pace, compared with slow pace, average pace was associated with HR 0.64 (0.60–0.68) and brisk pace with HR 0.53 (0.49–0.57) (Model 3). In the joint analysis, compared with participants who had both lower handgrip strength (Q1) and slow walking pace, the lowest risk was observed in those with both higher handgrip strength (Q2–Q4) and average or brisk walking pace (HR 0.51; 95% CI: 0.46–0.55). Results were robust to adjustment for a genetic risk score for eGFR, competing risk of death, and multiple sensitivity analyses. Stratified analyses showed no significant modification by most variables, though a potential interaction with age was noted.
**Clinical Implications:** This large prospective study provides the first robust evidence that simple, easily measured physical function indicators—handgrip strength and walking pace—are independently and jointly associated with incident CKD risk in the general population. The findings suggest that these measures, which can be assessed quickly in clinical settings, may help identify individuals at higher risk for CKD. Importantly, the combination of higher grip strength and faster walking pace was associated with a nearly 50% lower risk, highlighting the potential value of interventions targeting muscle strength and physical performance for CKD primary prevention. The associations persisted after adjustment for genetic risk, suggesting benefits may apply across the population. Limitations include the predominantly White, middle-aged/older cohort (limiting generalizability), potential healthy volunteer bias in UK Biobank, and the observational design precluding causal inference.