In hemodialysis patients with moderate to severe secondary hyperparathyroidism, cinacalcet plus low-dose vitamin D sterols may attenuate vascular and cardiac valve calcification.

Hepatic ischemia reperfusion injury (IRI) is not only a pathophysiological process involving the liver, but also a complex systemic process affecting multiple tissues and organs. Hepatic IRI can seriously impair liver function, even producing irreversible damage, which causes a cascade of multiple organ dysfunction. Many factors, including anaerobic metabolism, mitochondrial damage, oxidative stress and secretion of ROS, intracellular Ca(2+) overload, cytokines and chemokines produced by KCs and neutrophils, and NO, are involved in the regulation of hepatic IRI processes. Matrix Metalloproteinases (MMPs) can be an important mediator of early leukocyte recruitment and target in acute and chronic liver injury associated to ischemia. MMPs and neutrophil gelatinase-associated lipocalin (NGAL) could be used as markers of I-R injury severity stages. This review explores the relationship between factors and inflammatory pathways that characterize hepatic IRI, MMPs and current pharmacological approaches to this disease.

Vitamin K (vitamin K1 or phylloquinone and vitamin K2, a series of menaquinones [MKs]) is involved in the production of bone and matrix amino acid g-carboxy-glutamic acid (Gla) proteins, regulating bone and vascular calcification. Low vitamin K concentrations are associated with increased risks of fractures and vascular calcification, and frequent complications in hemodialysis patients. We carried out an observational study to establish the prevalence of vitamin K deficiency and to assess the relationship between vitamin K status, vertebral fractures, vascular calcification, and survival in 387 patients on hemodialysis for !1 year. We determined plasma levels of vitamin K compound, bone-Gla-protein, matrix-Gla-protein, and routine biochemistry. Vertebral fractures (reduction in vertebral body height by !20%) and aortic and iliac calcifications were also investigated in a spine (D 5 -L 4 ) radiograph. Three-year patient survival was analyzed. Important proportions of patients had deficiency of MK7 (35.4%), vitamin K1 (23.5%), and MK4 (14.5%). A total of 55.3% of patients had vertebral fractures, 80.6% had abdominal aorta calcification, and 56.1% had iliac calcification. Vitamin K1 deficiency was the strongest predictor of vertebral fractures (odds ratio [OR], 2.94; 95% confidence interval [CI], 1.38-6.26). MK4 deficiency was a predictor of aortic calcification (OR, 2.82; 95% CI, 1.14-7.01), whereas MK5 deficiency actually protected against it (OR, 0.38; 95% CI, 0.15-0.95). MK7 deficiency was a predictor of iliac calcification (OR, 1.64; 95% CI, 1.03-2.60). The presence of vertebral fractures was also a predictor of vascular calcifications (OR, 1.76; 95% CI, 1.00-3.08). Increased alkaline phosphatase and C reactive protein (CRP), age, and cerebrovascular events were predictors of mortality. Our study suggests that the vitamin K system may be important for preserving bone mass and avoiding vascular calcification in hemodialysis patients, pointing out a possible role of vitamin K in bone and vascular health. Based on our results, we suggest that the general population should also be studied for vitamin K deficiency as a possible cause of both vertebral fractures and vascular calcification. ß

Warfarin inhibits vitamin-K dependent proteins involved in bone mineralization and the prevention of vascular calcification (bone Gla protein BGP, matrix Gla protein MGP). In this multicenter, cross-sectional study with 3-year follow-up, data from 387 patients on hemodialysis for ≥1 year at 18 dialysis units were analyzed. Patients on warfarin treatment for > 1 year (11.9% of the population) were compared with the remaining cohort for vertebral fractures, vascular calcifications and mortality. Vertebral fractures and vascular calcifications were sought in L-L vertebral X-rays (D5 to L4). Compared with controls, warfarin-treated male patients had more vertebral fractures (77.8 vs. 57.7%, p<0.04), but not females (42.1% vs. 48.4%, p=0.6); total BGP was significantly reduced (82.35 vs. 202 µg/L, p<0.0001), with lower levels in treated men (69.5 vs. women 117.0 µg/L, p=0.03). In multivariate logistic regression analyses, the use of warfarin was associated with increased odds of aortic (OR 2.58, p<0.001) and iliac calcifications (OR 2.86, p<0.001); identified confounders were age, atrial fibrillation, angina, PPI use and total BGP. Seventy-seven patients died during a 2.7±0.5 year follow-up. In univariate Cox regression analysis, patients on warfarin had a higher risk of all-cause mortality (HR 2.42, 95% CI 1.42-4.16, p=0.001) when compared with those untreated and data adjustment for confounders attenuated but confirmed the significant warfarin-mortality link (HR: 1.97, 95% CI: 1.02-3.84, P=0.046). In hemodialysis patients, additional studies are warranted to verify the risk/benefit ratio of warfarin, which appears to be associated with significant morbidity and increased mortality.

To diagnose iron deficiency in patients undergoing hemodialysis, the percentage of hypochromic RBCs (with cellular hemoglobin concentration <280 g/L [HYPO%]) and mean reticulocyte hemoglobin content (CHret) provided by the Siemens ADVIA 120 and 2120 analyzers (Siemens Diagnostic Solutions, Tarrytown, NY) were proposed as alternatives to biochemical tests. Sysmex, with its XE-5000 analyzer (Sysmex, Kobe, Japan), also proposed the percentage of erythrocytes with cellular hemoglobin content lower than 17 pg (%Hypo-He) and equivalent of the mean reticulocyte hemoglobin content (Ret-He) with similar clinical applications. Our aim was to verify the clinical usefulness of the biochemical and cellular parameters as predictors of iron deficiency in patients undergoing long-term hemodialysis. We studied 69 patients undergoing hemodialysis 3 times weekly. The baseline values of serum ferritin and percentage of transferrin saturation were poor predictors of iron responsiveness. Better ability was demonstrated by reticulocyte indices (area under the curve [AUC], 0.74 for CHret and 0.72 for Ret-He; best cutoff values, 31.2 and 30.6 pg, respectively) and erythrocyte parameters (AUC, 0.72 for HYPO% and 0.68 for %Hypo-He; best cutoff values, 5.8 and 2.7, respectively). The newly proposed Ret-He and %Hypo-He can provide clinicians with information equivalent to CHret and HYPO%.