Cholecalciferol supplementation increases FGF23 in peritoneal dialysis patients with hypovitaminosis D: a randomized clinical trial.

BACKGROUND: Vitamin D deficiency is common in peritoneal dialysis (PD) patients, so its supplementation has been advocated as potentially beneficial. METHODS: Double-blind, placebo-controlled, randomized clinical trial. Subjects on PD treated with high calcium peritoneal dialysate (Ca 3.5 mEq/l) and serum levels of 25-hydroxi vitamin D (25D) < 20 ng/ml were randomized to receive cholecalciferol (4800 IU/daily) or placebo for 16 weeks. The outcome measures were the effects on the osteogenic biomarkers osteoprotegerin (primary endpoint), intact fibroblast growth factor-23 (iFGF23), osteocalcin, osteopontin, iPTH, 1,25-dyhydroxivitamin D (1,25D), and interleukin-6. RESULTS: Fifty-eight subjects were randomly assigned. Baseline characteristics were similar in both groups. Cholecalciferol supplemented subjects had a significant increase in serum 25D (from 11.4 ± 5.0 to 28.3 ± 10.3 ng/ml), 1,25D and iFGF23 compared with placebo group. iFGF23 levels increased an average of 10,875 pg/ml per month (95% CI 11,778-88,414) in the cholecalciferol group and was unchanged in the placebo group (2829 pg/ml, 95% CI - 2181 to 14,972). Extremely high iFGF23 levels (> 30,000 pg/ml) were observed in 74% of subjects receiving cholecalciferol although iFGF23 returned to baseline values after 32 weeks of withdrawal. The observed changes in iFGF23 correlated with 1,25D levels and were not modified by other variables. No difference was observed between groups in osteoprotegerin or other osteogenic biomarkers levels. CONCLUSIONS: Cholecalciferol supplementation increases serum 25D levels in subjects on PD exposed to high calcium dialysate, yet it induces an exponential increase of iFGF23 in most patients, which disappear after withdrawal of supplementation and may be a major concern for this maneuver.

Garlic powder ameliorates cisplatin-induced nephrotoxicity and oxidative stress.

cis-Diamminedichloroplatinum (II) (cisplatin) is an effective chemotherapeutic agent successfully used in the treatment of a wide range of tumors. Nevertheless, nephrotoxicity has restricted its clinical use. The use of more than a few antioxidants has shown that reactive oxygen species are involved in cisplatin-induced nephrotoxicity. In the present work the effect of garlic powder, a recognized antioxidant, on cisplatin-induced nephrotoxicity and oxidative and nitrosative stress was studied. Rats were fed with a 2% garlic powder diet for 4 weeks. A single injection of cisplatin (7.5 mg/kg) induced tubular damage and an increase in the following markers of renal injury 3 days later: blood urea nitrogen, serum creatinine, and urinary excretion of N-acetyl-beta-D-glucosaminidase. The cisplatin injection also increased 3-nitrotyrosine and 4-hydroxy-2-nonenal immunostaining in renal cortex and medulla. It was found that the garlic powder feeding was able to prevent by 40-59% the alterations in the markers of renal injury studied, by 33% the histological damage, and by 38-75% the increase in markers of oxidative and nitrosative stress. It is concluded that the ability of garlic powder to ameliorate cisplatin-induced renal injury is associated with its antioxidant properties. Our data support the use of garlic powder as a renoprotective agent.

S-allylcysteine ameliorates ischemia and reperfusion induced renal damage.

The effect of the garlic-derived antioxidant S-allylcysteine (SAC) on renal injury and oxidative stress induced by ischemia and reperfusion (IR) was studied in this work. Rats were anesthetized and subjected to right nephrectomy; 15 min later ischemia was induced for a period of 40 min and then the rats were subjected to a reperfusion period of 6 h after which they were killed to obtain blood and the left kidney. SAC was given at a dose of 100 mg/kg 30 min before nephrectomy, 15 min before ischemia, immediately before reperfusion and 2 h after reperfusion. IR-induced renal injury was evident by the increase in blood urea nitrogen (BUN) and serum creatinine as well as by the renal structural damage which was assessed by histological analysis. IR-induced oxidative stress was evident by the increase in immunostaining with 4-hydroxy-2-nonenal (4-HNE). SAC treatment was able to ameliorate the increase in BUN and serum creatinine and to decrease the structural damage. This protective effect was associated with a decrease in the immunostaining for 4-HNE. It is concluded that the antioxidant properties of SAC are involved in its protective effect on renal ischemia and reperfusion injury.

Protective effects of garlic powder against potassium dichromate-induced oxidative stress and nephrotoxicity.

Potassium dichromate (K(2)Cr(2)O(7))-induced nephrotoxicity is associated with oxidative stress. In the present work the effect of garlic powder, a recognized antioxidant, on K(2)Cr(2)O(7)-induced nephrotoxicity and oxidative stress was studied. Rats were fed a 2% garlic powder diet for 1 month. A single injection of K(2)Cr(2)O(7) (15 mg/kg) to rats induced tubule interstitial damage and an increase in the following markers of renal injury 2 days later: blood urea nitrogen (4.6-fold), serum creatinine (9.7-fold), proteinuria (35.9-fold), urinary excretion of N-acetyl-beta-d-glucosaminidase (12.9-fold) and glutathione-S-transferase (2.3-fold) and a decrease of 65% in serum glutathione peroxidase activity. In addition, K(2)Cr(2)O(7) injection increased the following nitrosative and oxidative stress markers in kidney: 3-nitrotyrosine (1.9-fold), 4-hydroxy-2-nonenal (2.1-fold), malondialdehyde (1.8-fold) and protein carbonyl content (1.7-fold). It was found that garlic powder feeding was able to prevent by 44-71% the alterations in the markers of renal injury studied, by 55% the histological damage, and by 47-100% the increase in markers of oxidative and nitrosative stress. It is concluded that the ability of garlic powder to ameliorate K(2)Cr(2)O(7)-induced renal injury is associated with its antioxidant properties. Our data support the use of garlic powder as a renoprotective agent.

Nordihydroguaiaretic acid attenuates potassium dichromate-induced oxidative stress and nephrotoxicity.

Larrea tridentata also known as Creosote bush, Larrea, chaparral, greasewood or gobernadora has been used in the folk medicine for the treatment of several illnesses. The primary product that is present at high concentrations in the leaves from this plant is nordihydroguaiaretic acid (NDGA) which is a powerful antioxidant. On the other hand, potassium dichromate (K(2)Cr(2)O(7))-induced nephrotoxicity is associated with oxidative stress. The aim of this work was to study the effect of NDGA on K(2)Cr(2)O(7)-induced nephrotoxicity and oxidative stress. Nephrotoxicity was induced by a single injection of K(2)Cr(2)O(7) (15 mg/Kg). A group of K(2)Cr(2)O(7)-treated rats was administered NDGA by mini osmotic pumps (17 mg/Kg/day). The results show that NDGA was able to ameliorate the structural and functional renal damage evaluated by histopathological analysis and by measuring proteinuria, urinary excretion of N-acetyl-beta-d-glucosaminidase, serum creatinine, and serum glutathione peroxidase activity. In addition, immunostaining of 4-hydroxy-2-nonenal and 3-nitrotyrosine, markers of oxidative and nitrosative stress, respectively, was ameliorated by the NDGA treatment. These data strongly suggest that the antioxidant properties of NDGA are involved in its renoprotective effect in K(2)Cr(2)O(7)-treated rats.

Renoprotective and antihypertensive effects of S-allylcysteine in 5/6 nephrectomized rats.

Progressive renal damage and hypertension are associated with oxidative and nitrosative stress. On the other hand, S-allylcysteine (SAC), the most abundant organosulfur compound in aged garlic extract (AG), has antioxidant properties. The effects of SAC and AG on blood pressure, renal damage, and oxidative and nitrosative stress were studied in five-sixths nephrectomized rats treated with SAC (200 mg/kg ip) and AG (1.2 ml/kg ip) every other day for 30 days. Proteinuria and serum creatinine and blood urea nitrogen concentrations were measured on days 0, 5, 10, 15, and 30, and systolic blood pressure was recorded on days 0, 15, and 30. The degree of glomerulosclerosis and tubulointerstitial damage, the immunostaining for inducible nitric oxide synthase, 3-nitrotyrosine, poly(ADP-ribose), and the subunits of NADPH oxidase p22phox and gp91phox, and the activity of SOD were determined on day 30. SAC and AG reduced hypertension, renal damage, and the abundance of inducible nitric oxide synthase, 3-nitrotyrosine, poly(ADP-ribose), p22phox, and gp91phox and increased SOD activity. Our data suggest that the antihypertensive and renoprotective effects of SAC and AG are associated with their antioxidant properties and that they may be used to ameliorate hypertension and delay the progression of renal damage.