[Vitamin D metabolism in kidney insufficiency: disorders of an endocrine regulatory zone].
The vitamin metabolite 25(OH)D is transformed into the active secosterole 1.25(OH)2D3 in the proximal tubular epithelium of the kidney. This transformation is disturbed in patients with renal insufficiency. However, this review shows that presumably not all vitamin D dependent disturbances in patients with renal insufficiency are explicable merely as the consequence of reduced renal synthesis of 1.25(OH)2D3 secondary to nephronal loss. In incipient renal failure, vitamin D dependent functions (calcemic action of PTH, intestinal absorption of Ca) are disturbed. Yet, circulating 1.25(OH)2D3 levels are slightly elevated. This finding is compatible with an inadequate response of the renal 1-alpha-hydroxylase system to activating stimuli (hyperparathyroidism, hypocalcemia, fasting hypophosphatemia) and/or end-organ resistance to the action of 1.25(OH)2D3. Osteomalacia in renal insufficiency cannot entirely be explained as the consequence of a reduction of the serum-concentration of any of the known vitamin D metabolites [25(OH)D3; 1.25(OH)2D3; 24.25(OH)2D3]. The relatively poor response of osteomalacia of uremic patients to the administration of 1.25(OH)2D3 leads to the question of whether other vitamin D metabolites or non-vitamin D related factors are important in its genesis. Critical information is lacking with respect to 1.25(OH)2D3 receptors, post receptor events and interaction between vitamin D metabolites and PTH in bone cells of such patients. A specific action of 1.25(OH)2D3 on longitudinal growth of uremic children has been described. However, several clinical and experimental studies failed to provide evidence of normalization of growth by 1.25(OH)2D3 and failed to show differences in this respect between vitamin D and 1.25(OH)2D3. Currently, it remains undecided whether vitamin D metabolites affect PTH secretion, and if so which vitamin D metabolite is involved. Clarification of this problem is of paramount importance for the therapeutic suppression of the parathyroids of uremic patients. Vitamin D metabolites play an important role in some organ functions unrelated to homeostasis of Ca-Pi-metabolism (e.g. muscle, testis, pancreas, etc). The loss of such function is of potential importance in the genesis of the uremic syndrome and its imcomplete reversal by hemodialysis.
D000042:Absorption; D000328:Adult; D000818:Animals; D002118:Calcium / Q000378:metabolism; D002648:Child; D012080:Chronic Kidney Disease-Mineral and Bone Disorder / Q000378:metabolism; D006130:Growth Disorders / Q000378:metabolism; D006801:Humans; D006961:Hyperparathyroidism / Q000378:metabolism; D007676:Kidney Failure, Chronic / Q000378:metabolism*; D010018:Osteomalacia / Q000378:metabolism; D010281:Parathyroid Hormone / Q000378:metabolism; D010710:Phosphates / Q000378:metabolism; D051381:Rats; D012632:Secosteroids / Q000378:metabolism; D014511:Uremia / Q000378:metabolism; D014807:Vitamin D / Q000378:metabolism* / Q000627:therapeutic use; D014808:Vitamin D Deficiency / Q000378:metabolism
D010281:Parathyroid Hormone; D010710:Phosphates; D012632:Secosteroids; D014807:Vitamin D; D002118:Calcium
Vitamin D-Metabolismus bei Niereninsuffizienz - Störung eines endokrinen Regelkreises.