#3439 EXERCISE, METABOLIC SYNDROME AND CHRONIC KIDNEY DISEASE (CKD): THE EX-RED STUDY
Authors: Febles Raúl Morales , Martín Amelia González , Báez Daniel Sánchez , Mallén Patricia Isabel Delgado , Miquel Rosa , Torres Sara Estupiñan , Caso Maria Angeles Cobo , Perera Coriolano Cruz , Martin Laura Díaz , Luis-Lima Sergio , Rinne Federico Gonzalez , Porrini Esteban 
Published: June 2023

Abstract

Background and aims
Obesity and metabolic syndrome (MS) are risk factors for renal disease progression in patients with established chronic kidney disease (CKD). Although therapeutic exercise has a potential role to treat or ameliorate chronic diseases, the effect of this intervention on obesity/MS and major renal outcomes: proteinuria and/or glomerular filtration rate (GFR) in patients with CKD is scarcely known. In particular, the effect of exercise in short term changes in renal outcomes are unknown. So, the aim of the study is to evaluate the effect of therapeutic exercise on: (a) the amelioration of MS traits and (b) renal parameters, GFR and proteinuria, in patients with CKD and MS.

Method
This is a 6-month exploratory study that included clinically stable patients with CKD of different causes and MS with measured GFR of 30-90 ml/min/kg2. Patients were treated with an incremental protocol of exercise which was prescribed by a physiotherapist. Baseline treatment and increments in prescription were based on physical status and individual response on follow-up, treatment involved both aerobic and strength exercise. All patients start with aerobic exercise training 30-60 minutes and 5 times per week. Strength exercise was individualized and consisted of free weight exercises. The prescription was incremented every month. The following outcomes were considered: changes in GFR i.e., ≥ 7%, which is twice the variability of the method in our laboratory (https://lfr.ecihucan.es), and weight lost ≥ 5%, a change associated to lower cardiovascular risk. In parallel with exercise training, we designed a plan to evaluate and promote adherence using regular telephone calls, an activity tracker, and visits to the hospital. Measured glomerular filtration rate (iohexol-DBS), urine samples (albuminuria/proteinuria), anthropometric parameters and analytics were collected at baseline, 3 and 6 months. There is no evidence in the field to evaluate the sample size of the study. Then, we designed and explorative study including 40 cases.

Results
This is a preliminary analysis of 25 cases: 3 were lost of follow-up at 3 months, and so, we show data of 22 patients that finished the study. Mean age was 58 y ± 12 and 70% (N = 17) were male. All patients were obese or overweight and 17 (70%) were diabetic. The most frequent kidney diseases were glomerulonephritis (40%) and diabetic nephropathy (30%). Most patients were on ACE inhibitors/ARAs (96%) and lipid-lowering agents (52%). At 6 months, 5 (22%) patients did not have major changes in weight, which was attributed to low adherence to treatment, and so, were not considered for further analyses. Of the remaining cases (N = 17, 78%), all showed a reduction in weight: from 97 kg ± 18 to 87 ± 18, p˂0.001. These patients were then classified in 3 groups based on GFR changes: (A) decreased GFR (N = 6, 35%), with GFR changing from 54 ml/min ± 13 to 44 ± 14, p = 0.001; BMI decreasing from 33 kg/m2 ± 4 to 30 ± 5, p = 0.003 and TG from 211 mg/dL ± 98 to 127 ± 59, p = 0.026; (B) stable GFR (N = 7, 41%), GFR from 47 ml/min ± 22 to 46 ± 21, p = 0.2; BMI decreasing from 35 kg/m2 ± 3 to 31 ± 3, p = 0.002 and TG from 160 mg/dL ± 57 to 105 ± 29, p = 0.02; (C) increased GFR (N = 4, 24%), GFR increasing from 59 ml/min ± 16 to 66 ± 18; p = 0.015 and BMI decreasing from 39 kg/m2 ± 3 to 36.5 ± 2, p = 0.015. No significant changes were observed in albuminuria and other MS traits in the subgroups analyzed. No adverse events were found during follow-up.

Conclusion
exercise is an effective and safe intervention method to lose weight and improve dyslipidaemia in patients with MS and CKD. The effect of weight reduction on GFR is not universal. Some patients showed a reduction of GFR in line with the reduction of weight, which may reflect the correction of hyperfiltration related to obesity and MS. On the other hand, in some patients GFR remained stable or even increased after weight loss. The pathogenesis behind this aspect is clearly unexpected and unknown. The impact of GFR changes associated with weight and MS changes in CKD deserve detailed attention in ad hoc designed studies.