Vitamin D and Glomerulonephritis

Abstract

Vitamin D presents a plethora of different functions that go beyond its role in skeletal homeostasis. It is an efficient endocrine regulator of the Renin–Angiotensin–Aldosterone System (RAAS) and erythropoiesis, exerts immunomodulatory effects, reduces the cardiovascular events and all-cause mortality. In Chronic Kidney Disease (CKD) patients, Vitamin D function is impaired; the renal hydrolyzation of its inactive form by the action of 1α-hydroxylase declines at the same pace of reduced nephron mass. Moreover, Vitamin D major carrier, the D-binding protein (DBP), is less represented due to Nephrotic Syndrome (NS), proteinuria, and the alteration of the cubilin–megalin–amnionless receptor complex in the renal proximal tubule. In Glomerulonephritis (GN), Vitamin D supplementation demonstrated to significantly reduce proteinuria and to slow kidney disease progression. It also has potent antiproliferative and immunomodulating functions, contributing to the inhibitions of kidney inflammation. Vitamin D preserves the structural integrity of the slit diaphragm guaranteeing protective effects on podocytes. Activated Vitamin D has been demonstrated to potentiate the antiproteinuric effect of RAAS inhibitors in IgA nephropathy and Lupus Nephritis, enforcing its role in the treatment of glomerulonephritis: calcitriol treatment, through Vitamin D receptor (VDR) action, can regulate the heparanase promoter activity and modulate the urokinase receptor (uPAR), guaranteeing podocyte preservation. It also controls the podocyte distribution by modulating mRNA synthesis and protein expression of nephrin and podocin. Maxalcalcitol is another promising alternative: it has about 1/600 affinity to vitamin D binding protein (DBP), compared to Calcitriol, overcoming the risk of hypercalcemia, hyperphosphatemia and calcifications, and it circulates principally in unbound form with easier availability for target tissues. Doxercalciferol, as well as paricalcitol, showed a lower incidence of hypercalcemia and hypercalciuria than Calcitriol. Paricalcitol demonstrated a significant role in suppressing RAAS genes expression: it significantly decreases angiotensinogen, renin, renin receptors, and vascular endothelial growth factor (VEGF) mRNA levels, thus reducing proteinuria and renal damage. The purpose of this article is to establish the Vitamin D role on immunomodulation, inflammatory and autoimmune processes in GN.

Gender Differences in Diabetic Kidney Disease: Focus on Hormonal, Genetic and Clinical Factors

“…Thus, vitamin D acts as a real steroid hormone and its level is influenced by estrogen status [ 133 ]. It exerts a modulating action at both tubular [ 134 ] and glomerular level [ 135 ], with peculiar protective action in DKD [ 136 ]. Moreover, pre- and post-menopausal DM women with an adequate vitamin D status seem to have a better glycemic control [ 137 ].…”

Vitamin D status in children and adolescents with type 1 diabetes in a specialized diabetes care centre in Bangladesh

“…Vitamin D acts as a real steroid hormone and its level is influenced by estrogen status 17 with protective action in DKD 18 . Vitamin D supplementation has also been demonstrated to significantly reduce proteinuria and slow kidney disease progression 19 …”

Cardiorenal Syndrome: New Pathways and Novel Biomarkers

“…Notwithstanding the pleiotropic effects that vitamin D exerts to prevent different conditions leading to renal impairment [ 58 , 59 , 60 ] to modulate renin-angiotensin-aldosterone system and to reduce CV risk [ 61 ], a connection with this hormone has not been fully validated in CRS patients. Mann et al [ 62 ] demonstrated that deficient serum levels of vitamin D are linked to a suppression of resting cardiac autonomic activity, while low 1,25-dihydroxy vitamin D levels correlated with unfavorable cardiac autonomic activity during an acute angiotensin II stressor challenge.…”