https://www.thelancet.com/pdfs/journals/lancet/PIIS0140-6736(14)61375-1.pdf

Cushing's syndrome

Bone metabolism and disease in chronic kidney disease

Note: This article was originally published with an incorrect version of the Acknowledgments, which appeared on p. 218 of the print version. The correct version of the Acknowledgments appeared on pp. 1–2. The corrected article is available below.

/pdf/human-health-risk-assessment-for-aluminium-aluminium-oxide-5dfetd69xm.pdf

Human Health Risk Assessment for Aluminium, Aluminium Oxide, and Aluminium Hydroxide

Soft-tissue calcification is a prominent feature in both chronic kidney disease (CKD) and experimental Klotho deficiency, but whether Klotho deficiency is responsible for the calcification in CKD is unknown. Here, wild-type mice with CKD had very low renal, plasma, and urinary levels of Klotho. In humans, we observed a graded reduction in urinary Klotho starting at an early stage of CKD and progressing with loss of renal function. Despite induction of CKD, transgenic mice that overexpressed Klotho had preserved levels of Klotho, enhanced phosphaturia, better renal function, and much less calcification compared with wild-type mice with CKD. Conversely, Klotho-haploinsufficient mice with CKD had undetectable levels of Klotho, worse renal function, and severe calcification. The beneficial effect of Klotho on vascular calcification was a result of more than its effect on renal function and phosphatemia, suggesting a direct effect of Klotho on the vasculature. In vitro, Klotho suppressed Na-dependent uptake of phosphate and mineralization induced by high phosphate and preserved differentiation in vascular smooth muscle cells. In summary, Klotho is an early biomarker for CKD, and Klotho deficiency contributes to soft-tissue calcification in CKD. Klotho ameliorates vascular calcification by enhancing phosphaturia, preserving glomerular filtration, and directly inhibiting phosphate uptake by vascular smooth muscle. Replacement of Klotho may have therapeutic potential for CKD.

Klotho Deficiency Causes Vascular Calcification in Chronic Kidney Disease

https://www.kidney-international.org/article/S0085-2538(15)57945-3/pdf

The spectrum of bone disease in end-stage renal failure—An evolving disorder

Osteomalacic dialysis osteodystrophy: Evidence for a water-borne aetiological agent, probably aluminium.

Ototoxicity of erythromycin in peritoneal dialysis patients.

Assessment of glomerular filtration rate during pregnancy using the MDRD formula

PERITONITIS IN CONTINUOUS AMBULATORY PERITONEAL DIALYSIS: Laboratory and Clinical Studies

Correction of acidosis in hemodialysis patients increases the sensitivity of the parathyroid glands to calcium. In this study, the parathyroid response to the correction of acidosis in eight hemodialysis patients was determined by performing dynamic assessment of parathyroid function before and after the correction of acidosis. The parathyroid response to intravenous calcitriol before and after the correction of acidosis was also assessed. After optimal correction of acidosis, there were no significant changes in blood pH, ionized calcium, phosphate, or alkaline phosphatase values, but the level of venous total CO2 increased significantly. Parathyroid hormone/ionized calcium curves were displaced downward after correction of acidosis, but not after the administration of intravenous calcitriol. The correction of metabolic acidosis in hemodialysis patients with secondary hyperparathyroidism can suppress parathyroid hormone secretion by increasing the sensitivity of the parathyroid glands to ionized calcium.

M. K. Ward

Papers

Osteomalacic dialysis osteodystrophy: Evidence for a water-borne aetiological agent, probably aluminium.

Ototoxicity of erythromycin in peritoneal dialysis patients.

Assessment of glomerular filtration rate during pregnancy using the MDRD formula

PERITONITIS IN CONTINUOUS AMBULATORY PERITONEAL DIALYSIS: Laboratory and Clinical Studies

Correction of acidosis in hemodialysis patients increases the sensitivity of the parathyroid glands to calcium.