An updated review of the existing knowledge regarding uremic toxins facilitates the design of experimental studies. We performed a literature search and found 621 articles about uremic toxicity published after a 2003 review of this topic. Eighty-seven records provided serum or blood measurements of one or more solutes in patients with CKD. These records described 32 previously known uremic toxins and 56 newly reported solutes. The articles most frequently reported concentrations of β2-microglobulin, indoxyl sulfate, homocysteine, uric acid, and parathyroid hormone. We found most solutes (59%) in only one report. Compared with previous results, more recent articles reported higher uremic concentrations of many solutes, including carboxymethyllysine, cystatin C, and parathyroid hormone. However, five solutes had uremic concentrations less than 10% of the originally reported values. Furthermore, the uremic concentrations of four solutes did not exceed their respective normal concentrations, although they had been previously described as uremic retention solutes. In summary, this review extends the classification of uremic retention solutes and their normal and uremic concentrations, and it should aid the design of experiments to study the biologic effects of these solutes in CKD.

Summary: Secondary hyperparathyroidism (SHPT) is a challenge frequently encountered in the management of patients with chronic kidney disease (CKD). Downregulation of the parathyroid vitamin D and calcium-sensing receptors represent critical steps that lead to abnormalities in mineral metabolism: high phosphate, low calcium, and vitamin D deficiency. These imbalances result in parathyroid hyperplasia and contribute to vascular calcification. New studies have established a central role for fibroblast growth factor 23 (FGF-23) in the regulation of phosphate-vitamin D homeostasis. FGF-23 concentration increases in CKD and contributes to SHPT. Achieving current targets for the key mineral parameters in the management of SHPT set by the Kidney Disease Improving Global Outcomes (KDIGO) guidelines can be challenging. This review summarizes the current understanding and evidence supporting strategies for SHPT treatment in CKD patients. Treatment should include a combination of dietary phosphorus restriction, phosphate binders, vitamin D sterols, and calcimimetics. Parathyroidectomy is effective in suitable candidates refractory to medical therapy and the standard against which new approaches should be measured. Future strategies may focus on the stimulation of apoptotic activity of hyperplastic parathyroid cells.

Phosphorus retention is an important factor in the development of hyperparathyroidism secondary to renal failure. In vivo manipulation of phosphorus is associated with changes in serum calcium and calcitriol levels which in turn can modify parathyroid hormone synthesis and secretion. The present in vitro study evaluates whether high extracellular phosphorus has a direct effect on parathyroid hormone secretion. Fresh rat parathyroid glands were incubated in a media with phosphorus concentrations of 1, 2, 3, and 4 mM and subsequently exposed to calcium levels ranging from 0.4 to 1.35 mM. In 1.25 mM calcium, the parathyroid hormone secretion rate was similar in 1 and 2 mM phosphorus; however, a phosphorus concentration of 3 and 4 mM produced a 3- and 4-fold increase in the parathyroid hormone secretion, respectively, as compared with 1 mM phosphorus. While in 1 or 2 mM phosphorus an increase in calcium from 0.6 to 1.35 mM reduced parathyroid hormone secretion to 37%, in 4 mM phosphorus the same increase in calcium only inhibited parathyroid hormone secretion to 75%. Furthermore, the addition of arachidonic acid 20 μM, a substrate for inhibitory intracellular signal pathway, to the 4 mM phosphorus-1.35 mM calcium incubation media reduced the parathyroid hormone secretion to 34.5% (p < 0.05). In conclusion, our results indicate that in vitro, high phosphorus directly increases parathyroid hormone secretion. (J Bone Miner Res 1996;11:970-976)

The uremic syndrome is a complex mixture of organ dysfunctions, which is attributed to the retention of a myriad of compounds that under normal condition are excreted by the healthy kidneys (uremic toxins). In the area of identification and characterization of uremic toxins and in the knowledge of their pathophysiologic importance, major steps forward have been made during recent years. The present article is a review of several of these steps, especially in the area of information about the compounds that could play a role in the development of cardiovascular complications. It is written by those members of the Uremic Toxins Group, which has been created by the European Society for Artificial Organs (ESAO). Each of the 16 authors has written a state of the art in his/her major area of interest.