Treatment with 1, 25-Dihydroxyvitamin D3 Preserves Glomerular Slit Diaphragm-Associated Protein Expression in Experimental Glomerulonephritis

Fibroblast growth factor-23 is a bone-derived hormone that increases urinary phosphate excretion and inhibits hydroxylation of 25-hydroxyvitamin D. Recent studies suggest that fibroblast growth factor-23 may be an early biomarker of CKD progression. However, its role in kidney function decline in the general population is unknown. We assessed the relationship between baseline (1990-1992) serum levels of intact fibroblast growth factor-23 and incident ESRD in 13,448 Atherosclerosis Risk in Communities study participants (56.1% women, 74.7% white) followed until December 31, 2010. At baseline, the mean age of participants was 56.9 years and the mean eGFR was 97 ml/min per 1.73 m 2 . During a median follow-up of 19 years, 267 participants (2.0%) developed ESRD. After adjustment for demographic characteristics, baseline eGFR, traditional CKD risk factors, and markers of mineral metabolism, the highest fibroblast growth factor-23 quintile (.54.6 pg/ml) compared with the lowest quintile (,32.0 pg/ml) was associated with risk of developing ESRD (hazard ratio, 2.10; 95% confidence interval, 1.31 to 3.36; trend P,0.001). In a large, community-based study comprising a broad range of kidney function, higher baseline fibroblast growth factor-23 levels were associated with increased risk of incident ESRD independent of the baseline level of kidney function and a number of other risk factors.

Section: Discussionmentioning

confidence: 94%

Serum Fibroblast Growth Factor-23 Is Associated with Incident Kidney Disease

Rebholz

Grams

Coresh

et al. 2015

“…Active vitamin D analogues ameliorate renal function in a rat model of chronic allograft nephropathy, 29 in subtotally nephrectomized rats, 7,[30][31][32] and in other models of CKD. 8 34 reduction of glomerular inflammation, and reduction of tubular cell proliferation. 7 VDR signaling also interferes with important pathways of CKD progression, including the reninangiotensin system (RAS), 35 epidermal growth factor receptor, 36 and TGF-b signaling.…”

Section: Discussionmentioning

confidence: 99%

“…Of note, vitamin D signaling protects against progression of chronic renal lesions in different models of CKD. [7][8][9][10][11][12][13][14][15] More recently, calcitriol and paricalcitol, two agonists of VDR signaling, have been shown to lessen albuminuria in patients with IgA nephropathy 16 and diabetic nephropathy, 17 respectively. In addition, two community-based studies and a small observational study in patients with CKD who have not had transplantation found an association between low 25(OH)D levels and the risk of ESRD 18 or eGFR decline.…”

mentioning

confidence: 99%

Vitamin D Status and Outcomes After Renal Transplantation

Bienaimé

Girard

Anglicheau

et al. 2013

100

Kidney transplant recipients usually have low vitamin D levels, especially in the early posttransplantation period, but the association between vitamin D status with renal outcomes is not well described in this population. Here, we studied a prospective cohort of 634 kidney recipients who underwent transplantation at a single institution between January 2005 and June 2010. In this cohort, low 25-hydroxyvitamin D concentrations 3 months after transplantation did not predict early death or graft loss but were independently associated with lower measured GFR at 12 months (P=0.001) and higher risk for interstitial fibrosis and tubular atrophy (P=0.01). In contrast, levels of calcium, phosphorus, calcitriol, parathyroid hormone, or fibroblast growth factor-23 were not consistently associated with any of the studied outcomes. In conclusion, low 25-hydroxyvitamin D concentration measured 3 months after transplantation is an independent risk factor for interstitial fibrosis progression and is associated with a lower GFR 1 year after transplantation. 24: 831-841, 201324: 831-841, . doi: 10.1681 Kidney transplantation is the preferred treatment for the increasing number of patients with ESRD. Transplantation allows patients to avoid the heavy constraints associated with dialysis therapy and is associated with a lower mortality and morbidity than is hemodialysis. 1 Evolution of GFR in transplant recipients appears to be imprinted at an early stage after the surgery. Indeed, the estimated GFR (eGFR) reached 1 year after transplantation is critically associated with allograft outcome. 2,3 This observation prompts research on modifiable factors affecting GFR in the first year after transplantation. J Am Soc NephrolVitamin D is a critical hormone controlling mineral homeostasis. It promotes phosphate and calcium absorption by the gut and increases calcium reabsorption by the renal distal tubule, thereby providing the positive calcium and phosphorus flux required for bone mineralization.

“…39 In the anti-Thy 1.1 model of glomerulonephritis, rats treated with 1,25(OH) 2 D 3 had less albuminuria 40 and showed preserved slit diaphragm protein morphology. 9 22-Oxacalcitriol, a vitamin D analog, reduced urine albumin excretion and prevented mesangial cell proliferation and extracellular matrix expansion in two different rat models of glomerulosclerosis. 10,41 Mesangial cell proliferation and extracellular matrix expansion are two of the pathologic processes that lead to progressive glomerulosclerosis.…”

Section: Clinical Epidemiology Wwwjasnorgmentioning

confidence: 99%

“…Activated vitamin D, 1,25-dihydroxyvitamin D [1,25(OH)2D], suppresses renin biosynthesis in mice, and vitamin D deficiency stimulates renin production. 8 In different animal models, 1,25(OH)2D or its analogs reduced proteinuria levels; preserved glomerular podocyte structure 9 ; decreased levels of TGF-␤1, an inducer of renal fibrosis; and inhibited mesangial cell proliferation, a marker of renal injury. 10 Low 25(OH)D levels were associated with albuminuria in a cross-sectional analysis of NHANES III.…”

mentioning

confidence: 99%

25-Hydroxyvitamin D Levels, Race, and the Progression of Kidney Disease

Melamed

Astor

Michos

et al. 2009

173

131

Black individuals have lower 25-hydroxyvitamin D [25(OH)D] levels and experience a disproportionate burden of ESRD compared with white individuals. Animal studies suggest that vitamin D has renoprotective effects. We evaluated the contribution of low 25(OH)D levels on incidence of ESRD using data from the Third National Health and Nutrition Examination Survey-linked Medicare claims files (n ϭ 13,328). We included baseline (1988 through 1994) measurements of 25(OH)D and assessed the incidence of ESRD through July 31, 2001. Overall, 34% of non-Hispanic black individuals had 25(OH)D levels Ͻ15 ng/ml compared with 5% of non-Hispanic white individuals (P Ͻ 0.001). During a median of 9.1 yr, 65 participants developed ESRD. After adjustment for demographic, socioeconomic, and clinical and laboratory factors (including diabetes, hypertension, estimated GFR, and albuminuria), participants with 25(OH)D levels Ͻ15 ng/ml had a 2.6-fold greater incidence of ESRD than those with levels Ն15 ng/ml (incidence rate ratio 2.64; 95% confidence interval [CI] 1.00 to 7.05; P ϭ 0.05). After adjustment for clinical covariates but not 25(OH)D levels, non-Hispanic black individuals had a 2.83-fold (95% CI 1.03 to 7.77) higher risk for developing ESRD compared with non-Hispanic white individuals. Additional adjustment for 25(OH)D levels reduced the risk by 58% (incidence rate ratio 1.77; 95% CI 0.38 to 8.21). In summary, low 25(OH)D levels associate with development of ESRD even after adjustment for multiple risk factors. Low 25(OH)D levels may account for a substantial proportion of the increased risk for ESRD experienced by black individuals.