Relationship between biochemical parameters and serum kynurenine pathway, body composition, muscle mass, and osteoporosis in patients with chronic renal failure

Objective: The aim of our study was to investigate the effects of kynurenine pathway metabolites on biochemical parameters, osteoporosis and body composition in individuals with CKD and also the relationship between these parameters. Methods: Our study was planned as a single-center, prospective and controlled study. Our study included 100 chronic kidney patients over the age of 18, GFR<60 ml/min and not on dialysis, 60 chronic kidney patients on dialysis and 42 people without known chronic disease who applied to Selçuk University Faculty of Medicine Internal Medicine Polyclinic between January 2024 and November 2024. A total of 202 patients were included. Participants in our study were grouped according to the KDIGO 2012 guideline CKD GFR stages. 72 patients with Stage 5, 26 with Stage 4, 27 with Stage 3b and 35 with Stage 3a were selected. A total of 10 dialysis patients were excluded from the study because bone densitometry could not be performed due to mobility limitations and patient noncompliance. The study was completed with 192 patients in total. At the beginning of the study, the patients' age, gender, comorbidities, and medications used were recorded. GFR, creatinine, urea, albumin, sodium, potassium, calcium, phosphorus, magnesium, chlorine, uric acid, total protein, glucose, alkaline phosphatase, hemogram, CRP, Parathotmon, vitamin D, vitamin B12, folate, ferritin, venous blood gas, spot urine microalbumin/creatinine, spot urine protein/creatinine were studied. In addition, waste blood taken during routine controls was not thrown away but stored under appropriate conditions and 3-OH anthranilic acid, 3-OH kynurenine, kynurenic acid, kynurenine and tryptophan levels were checked. Waist circumference, hip circumference, height, weight, body fat mass, fat-free mass measurement, total body fluid, intracellular fluid, extracellular fluid, third space fluid, body mass index, basal metabolic rate, nutritional index and body composition analysis were performed on the patients with the bioimpedance device in the Hemodialysis Unit. In addition, bone mineral densitometry measurements were performed on the patients and treatment of patients with osteoporosis was started. All data were evaluated using the SPSS 21.0 statistical package program. Criteria such as number, percentage, mean and standard deviation were used to calculate the data. Pearson correlation analyzes were used to evaluate the relationship between numerical variables. The significance level was taken as p<0.005. 78 Results: Of the 192 patients included in the study, 52.7% of the CKD group were male and 47.3% were female. In the control group, 45.2% were men and 54.8% were women. The average age of the patients was 59.43±10.73 in the CKD group and 56.64±5.31 in the control group.It was determined that the levels of 3-OH anthranic acid, kynurenic acid and kynurenine, which are the metabolites of the kynurenine pathway, were statistically significantly higher in the CKD group than in the control group, while the tryptophan level was statistically significantly lower than the control group. When the CKD group was compared according to stages, the kynurenine level was found to be statistically significantly higher in Stage 5 compared to the other stages of CKD. It was observed that the tryptophan level was statistically significantly lower in Stage 5 compared to other stages of CKD. In the CKD group, a negative relationship was found between kynurenic acid, kynurenine levels and GFR level, and a positive relationship was found between creatine level. There was a positive relationship between tryptophan level and GFR level and a negative relationship between creatine level. It was observed that the levels of 3-OH Anthranilic acid, 3-OH kynurenine, Kynurenic acid and kynurenine in dialysis patients in the CKD group were statistically significantly higher before dialysis than after dialysis. Waist circumference, hip circumference, body mass index, waist/hip ratio, total body fluid and extracellular fluid were found to be higher in the CKD group compared to the control group. L1-L2, L1-L3, L2-L3, L3-L4, neck, upper neck, WARDS score, trochanter and total T scores were found to be statistically significantly lower in the CKD group compared to the control group. In the CKD group, a statistically significant, low and insignificant negative correlation was found between kynurenic acid level and L3, L4, L1-L4, L2-L3, L2-L4, L3-L4 T scores. In the CKD group, a positive, statistically significant, low-insignificant correlation was detected between tryptophan level and L3, L4, L1-L4, L2-L3, L2-L4, L3-L4 and trochanter T scores. Conclusion: In our study, we found that metabolites formed as a result of tryptophan catabolism (kynurenine pathway) increased in individuals with CKD. These metabolites were observed to be at the highest level in CKD stage 5. We found a positive correlation between these molecules and creatine level and a negative correlation with eGFR. In our study, we found that there was a negative relationship between kynurenic acid, one of the metabolites formed as a result of tryptophan catabolism, and osteoporosis and BMD, and a positive relationship with tryptophan. In the literature, there are animal studies investigating the relationship between metabolites formed as a result of tryptophan catabolism and osteoporosis and BMD, but human studies are limited. Expanding studies examining the relationship between tryptophan catabolism (kynurenine pathway) and osteoporosis in CKD not only makes the kynurenine pathway a potential target for osteoporosis treatment in the future, but may also be useful in preventing the development of osteoporosis in the early stages of CKD.