#2123 Ageing, renal function and frailty: analysis of the FRASNET study
Authors: Lanzani Chiara Livia , Simonini Marco , Citterio Lorena , Zagato Laura , Brioni Elena , Damanti Sarah , Messaggio Elisabetta , Concas Maria Pina , Querini Patrizia Rovere , Manfredi Angelo , Manunta Paolo 
Published: May 2024

Abstract

Background and Aims
Frailty is a common geriatric syndrome of significant public health importance. The kidney is one of the organs that progressively loses function with aging leading a decrease of glomerular filtration rate (GFR). In elderly the definition of eGFR threshold for the diagnosis of CKD is debated.
FRASNET study aims of identify the role of kidney function (glomerular and tubular involvement) in determining frailty among not community-dwelling elderly adults, also depending on the genetics of each single subject.

Method
The FRASNET study was a cross-sectional multicentre observational cohort study involving healthy. The exclusion criteria were: i) severe cognitive impairment, ii) severe health problems. They have been characterised for BP, GFR, sodium intake (Kawasaki formula), cognitive status, quality of life, anamnestic factors, health and socio-economic status. Frailty was determined according to modified Fried index by the presence of three conditions among reduced grip strength, reduced gait speed, low physical activity, self-reported exhaustion. We considered the number of drugs as an index of comorbidity. Genotyping of 20 targeted single nucleotide polymorphisms (SNPs) selected on renal and hypertension was performed. ANOVA and conditional inference tree analysis have been carried out.

Results
1183 individuals were included in the study sample. Median age was 72 [IQ 69-77]. 328 (27.7%) subjects were robust, 445 (37.6%) pre-frail, 410 (34.7%) frail. Frailty increases with age, especially after 75 years (from 28.9% to 75.7%).
The overall mean GFR was 71.8 ± 16.5 ml/min/1.73 m2.
Estimated 24 h urinary sodium excretion was 194.5 mEq/24 h with median fractional excretion of sodium (FeNa) 0.75%. In 31.9% of sample FeNa was greater than 1%.
Only 3% of subjects reported CKD. Moreover, 21.1% presented eGFR ≤ 60 and the prevalence of CKD increases according to age from 12.3% to 70.3%. CKD prevalence increases in linear manner across frailty classes from 20% in robust to 47.6% in frail. Conditional inference tree analysis confirmed the role of age, comorbidity and GFR in determining frailty. In oldest subjects (&gt;75 years old), the eGFR level most strongly associated with frailty was below 53 (ml/min/1.73 m2) (Fig. 1).
No differences in sodium excretion were observed according to frailty classes.
Moreover, we observed an increase of FeNa according to age and frailty classes form 0.71% (median (IQR 0.567)) to 0.79% (median (IQR 0.690)).
In frail group exaggerated FeNa (&gt;1%) is more frequent than in robust and pre-frail subjects (Chi-squared p = 0.021).
Even after the introduction of these variables in inferential trees the new proposed cut-off for GFR (53) is a main determinant of frailty in oldest (Fig. 2).
The eGFR parameter resulted associated with two genetic variants in RAAS system, rs5051 in the angiotensinogen gene (AGT) and rs2131127 in the angiotensin II receptor type 1 (AGTR1). The rs4293393 in uromodulin gene (UMOD) was confirmed associated with eGFR value.

Conclusion
The present study is part of the complex debate on the relationship among renal function, aging and frailty.
We can therefore conclude that glomerular filtration (eGFR below 50 and not the presence of CKD) must be considered among the factors that influence frailty.
Our study also showed a deterioration of tubular function in frail subject that can be expression of structural changes due to nephroangiosclerosis.