Association between Uremic Toxin Concentrations and Bone Mineral Density after Kidney Transplantation

Abstract

Although uremic osteoporosis is a component of mineral and bone disorder in chronic kidney disease, uremic toxin (UT) concentrations in patients with end-stage kidney disease and bone mineral density (BMD) changes after kidney transplantation have not previously been described. We hypothesized that elevated UT concentrations at the time of transplantation could have a negative impact on bone during the early post-transplantation period. Hence, we sought to determine whether concentrations of UTs (trimethylamine-N-oxide, indoxylsulfate, p-cresylsulfate, p-cresylglucuronide, indole-3-acetic acid, hippuric acid, and 3-carboxy-4-methyl-5-propyl-furanpropionic acid) upon transplantation are predictive markers for (i) osteoporosis one month after transplantation, and (ii) a BMD decrease and the occurrence of fractures 12 and 24 months after kidney transplantation. Between 2012 and 2018, 310 kidney transplant recipients were included, and dual-energy X-ray absorptiometry was performed 1, 12, and 24 months after transplantation. The UT concentrations upon transplantation were determined by reverse-phase high-performance liquid chromatography. Indoxylsulfate concentrations upon transplantation were positively correlated with BMD one month after transplantation for the femoral neck but were not associated with osteoporosis status upon transplantation. Concentrations of the other UTs upon transplantation were not associated with osteoporosis or BMD one month after transplantation. None of the UT concentrations were associated with BMD changes and the occurrence of osteoporotic fractures 12 and 24 months after transplantation. Hence, UT concentrations at the time of kidney transplantation were not predictive markers of osteoporosis or fractures.

Prevalence of Musculoskeletal and Metabolic Disorders in Kidney Transplant Recipients: A Systematic Review and Meta-Analysis

“…As for the other variables, we can observe the large difference in prevalence estimates between the transplanted population and the general population for hypercalcemia [ 54 ], hyperparathyroidism [ 55 ], hyperuricemia [ 55 ], hypervitaminosis D [ 56 ], sarcopenia [ 57 ], low muscle mass [ 58 ], fractures [ 59 ] and gout [ 55 ], indicating an increase in the prevalence of these metabolic disturbances and musculoskeletal disorders after kidney transplantation. In the case of osteopenia and osteoporosis, the difference in prevalence between the two populations is small, although it is true that in the studies [ 60 , 61 ] we have found in the general population, it is not divided into zones, as it is in the studies [ 13 , 15 , 19 – 21 , 24 , 25 , 29 , 35 – 37 , 39 , 43 ] in the transplanted population, which divide the prevalence into lumbar and femoral areas, so that no conclusions could be drawn when comparing the two populations with regard to these two variables analysed.…”

“…The characteristics of the studies selected for this systematic review and meta-analysis are detailed in Table 1 . The study design was cross-sectional in 27 studies [ 11 , 12 , 14 , 15 , 18 – 21 , 23 – 32 , 34 – 37 , 41 – 45 ] (71.1%) and longitudinal in 11 [ 13 , 16 , 17 , 22 , 33 , 38 – 40 , 46 – 48 ] (28.9%). All these articles were published between 2001 and 2021, and most of them were conducted in Europe [ 13 , 14 , 16 , 19 – 24 , 29 – 31 , 35 , 36 , 38 , 39 , 42 ] (44.7%), although there were also studies from Asia [ 11 , 18 , 25 – 27 , 34 , 37 , 40 , 43 , 45 , 46 , 48 ] (31.6%), America [ 15 , 17 , 28 , 32 , 33 , 44 , 47 ] (18.4%) and Oceania [ 12 , 41 ] (5.3%).…”

“…For low muscle strength, the overall prevalence was 64.5% (95% CI: 43.1–81.3; I 2 = 94.4), and the prevalence of low muscle mass was 39.5% (95% CI: 20.3–62.6; I 2 = 95.3) ( Supplementary Figures S2, S3 ). (b) Osteopenia and osteoporosis: Eleven articles [ 13 , 15 , 19 – 21 , 24 , 25 , 29 , 36 , 37 , 43 ] investigated the prevalence in the lumbar area, and 12 [ 13 , 15 , 19 – 21 , 24 , 29 , 35 – 37 , 39 , 43 ] studied the prevalence in the femoral area, with 3,021 and 3,339 transplant recipients, respectively. The prevalence of osteopenia in the lumbar area was 30.7% (95% CI: 23.3–39.3; I 2 = 95.1).…”

“…(b) Osteopenia and osteoporosis: Eleven articles [ 13 , 15 , 19 – 21 , 24 , 25 , 29 , 36 , 37 , 43 ] investigated the prevalence in the lumbar area, and 12 [ 13 , 15 , 19 – 21 , 24 , 29 , 35 – 37 , 39 , 43 ] studied the prevalence in the femoral area, with 3,021 and 3,339 transplant recipients, respectively. The prevalence of osteopenia in the lumbar area was 30.7% (95% CI: 23.3–39.3; I 2 = 95.1).…”

Liquid Chromatography-Mass Spectrometry Analytical Methods for the Quantitation of p-Cresol Sulfate and Indoxyl Sulfate in Human Matrices: Biological Applications and Diagnostic Potentials

“…However, the mechanisms and the cause-effect relationships between IxS and gastric cancer development remain to be further proven. Batteux et al [ 94 ] characterized osteoporosis as measured by bone mineral density (BMD) and by bone fractures after transplantation [ 94 ] ( Table 2 ). It was evident that serum IxS concentrations at the time of transplantation exhibited a positive relationship with BMD in the femoral neck and the total hip at one-month post-transplant [ 94 ], but p CS did not generate significant correlations.…”