Hypovitaminosis D in patients undergoing kidney transplant: the importance of sunlight exposure

OBJECTIVES: Recent studies have shown a high prevalence of hypovitaminosis D, defined as a serum 25-hydroxyvitamin D level less than 30 ng/ml, in both healthy populations and patients with chronic kidney disease. Patients undergoing kidney transplant are at an increased risk of skin cancer and are advised to avoid sunlight exposure. Therefore, these patients might share two major risk factors for hypovitaminosis D: chronic kidney disease and low sunlight exposure. This paper describes the prevalence and clinical characteristics of hypovitaminosis D among patients undergoing kidney transplant. METHODS: We evaluated 25-hydroxyvitamin D serum levels in a representative sample of patients undergoing kidney transplant. We sought to determine the prevalence of hypovitaminosis D, compare these patients with a control group, and identify factors associated with hypovitaminosis D (e.g., sunlight exposure and dietary habits). RESULTS: Hypovitaminosis D was found in 79% of patients undergoing kidney transplant, and the major associated factor was low sunlight exposure. These patients had higher creatinine and intact parathyroid hormone serum levels, with 25-hydroxyvitamin D being inversely correlated with intact parathyroid hormone serum levels. Compared with the control group, patients undergoing kidney transplant presented a higher prevalence of 25-hydroxyvitamin D deficiency and lower serum calcium, phosphate and albumin but higher creatinine and intact parathyroid hormone levels. CONCLUSIONS: Our results confirmed the high prevalence of hypovitaminosis D in patients undergoing kidney transplant. Therapeutic strategies such as moderate sunlight exposure and vitamin D supplementation should be seriously considered for this population

Bone Plasticity in Response to Exercise Is Sex-Dependent in Rats

Purpose: To characterize the potential sexual dimorphism of bone in response to exercise.Methods: Young male and female Wistar rats were either submitted to 12 weeks of exercise or remained sedentary. the training load was adjusted at the mid-trial (week 6) by the maximal speed test. A mechanical test was performed to measure the maximal force, resilience, stiffness, and fracture load. the bone structure, formation, and resorption were obtained by histomorphometric analyses. Type I collagen (COL I) mRNA expression and tartrate-resistant acid phosphatase (TRAP) mRNA expression were evaluated by quantitative real-time PCR (qPCR).Results: the male and female trained rats significantly improved their maximum speed during the maximal exercise test (main effect of training; p<0.0001). the male rats were significantly heavier than the females, irrespective of training (main effect of sex; p<0.0001). Similarly, both the weight and length of the femur were greater for the male rats when compared with the females (main effect of sex; p<0.0001 and p<0.0001, respectively). the trabecular volume was positively affected by exercise in male and female rats (main effect of training; p = 0.001), whereas the trabecular thickness, resilience, mineral apposition rate, and bone formation rate increased only in the trained males (within-sex comparison; p<0.05 for all parameters), demonstrating the sexual dimorphism in response to exercise. Accordingly, the number of osteocytes increased significantly only in the trained males (within-sex comparison; p<0.05). Pearson's correlation analyses revealed that the COL I mRNA expression and TRAP mRNA expression were positively and negatively, respectively, related to the parameters of bone remodeling obtained from the histomorphometric analysis (r = 0.59 to 0.85; p<0.05).Conclusion: Exercise yielded differential adaptations with respect to bone structure, biomechanical proprieties, and molecular signaling in male and female rats.Univ São Paulo, Sch Med, Div Nephrol, São Paulo, BrazilUniv São Paulo, Sch Phys Educ & Sport, Dept Sports, São Paulo, BrazilUniv São Paulo, Inst Biomed Sci, Dept Anat, São Paulo, BrazilUniv São Paulo, Sch Med, Div Rheumatol, São Paulo, BrazilUniversidade Federal de São Paulo, Dept Physiol Sci, São Paulo, BrazilUniversidade Federal de São Paulo, Dept Physiol Sci, São Paulo, BrazilWeb of Scienc

Serum sclerostin is an independent predictor of mortality in hemodialysis patients

Background\ud Sclerostin (Scl) has recently emerged as a novel marker of bone remodeling and vascular calcification. However, whether high circulating Scl is also a risk factor for death is not well established. The purpose of this study was to test whether serum Scl would be associated with mortality.\ud \ud \ud Methods\ud we measured serum Scl in a hemodialysis patients’ cohort, which was followed during a ten-year period. Competing risk regression models were applied, as during the follow-up, patients were exposed to both events kidney transplant and death.\ud \ud \ud Results\ud Ninety-one patients aged 42.3 ± 18.8 years (55% of male gender, 15% of diabetes) were included. During the follow-up, 32 patients underwent kidney transplant and 26 patients died. Non-survivals presented higher FGF23, higher Scl and lower creatinine. There was an association between all-cause mortality and higher Scl (HR = 2.2), higher age (HR = 1.04) and presence of diabetes (HR = 2.27), by competing risk analyses. Even including potential markers of mortality, as creatinine, FGF 23, and gender, Scl, age and diabetes remained significantly related to higher mortality.\ud \ud \ud Conclusion\ud Serum Scl is an independent predictor of mortality in dialysis patients. However, whether clinical interventions to modulate Scl would be able to improve these patients survival needs to be determined.Fapes

Transcription factor HNF4α2 promotes osteogenesis and prevents bone abnormalities in mice with renal osteodystrophy.

Renal osteodystrophy (ROD) is a disorder of bone metabolism that affects virtually all patients with chronic kidney disease (CKD) and is associated with adverse clinical outcomes including fractures, cardiovascular events, and death. In this study, we showed that hepatocyte nuclear factor 4α (HNF4α), a transcription factor mostly expressed in the liver, is also expressed in bone, and that osseous HNF4α expression was dramatically reduced in patients and mice with ROD. Osteoblast-specific deletion of Hnf4α resulted in impaired osteogenesis in cells and mice. Using multi-omics analyses of bones and cells lacking or overexpressing Hnf4α1 and Hnf4α2, we showed that HNF4α2 is the main osseous Hnf4α isoform that regulates osteogenesis, cell metabolism, and cell death. As a result, osteoblast-specific overexpression of Hnf4α2 prevented bone loss in mice with CKD. Our results showed that HNF4α2 is a transcriptional regulator of osteogenesis, implicated in the development of ROD

Phosphorus Is Associated with Coronary Artery Disease in Patients with Preserved Renal Function

High serum phosphorus levels have been associated with mortality and cardiovascular events in patients with chronic kidney disease and in the general population. In addition, high phosphorus levels have been shown to induce vascular calcification and endothelial dysfunction in vitro. The aim of this study was to evaluate the relation of phosphorus and coronary calcification and atherosclerosis in the setting of normal renal function. This was a cross-sectional study involving 290 patients with suspected coronary artery disease and undergoing elective coronary angiography, with a creatinine clearance >60 ml/min/1.73 m2. Coronary artery obstruction was assessed by the Friesinger score and coronary artery calcification by multislice computed tomography. Serum phosphorus was higher in patients with an Agatston score >10 than in those with an Agatston score ≤10 (3.63±0.55 versus 3.49±0.52 mg/dl; p = 0.02). In the patients with Friesinger scores >4, serum phosphorus was higher (3.6±0.5 versus 3.5±0.6 mg/dl, p = 0.04) and median intact fibroblast growth factor 23 was lower (40.3 pg/ml versus 45.7 pg/ml, p = 0.01). Each 0.1-mg/dl higher serum phosphate was associated with a 7.4% higher odds of having a Friesinger score >4 (p = 0.03) and a 6.1% greater risk of having an Agatston score >10 (p = 0.01). Fibroblast growth factor 23 was a negative predictor of Friesinger score (p = 0.002). In conclusion, phosphorus is positively associated with coronary artery calcification and obstruction in patients with suspected coronary artery disease and preserved renal function

Predictive Factors of One-Year Mortality in a Cohort of Patients Undergoing Urgent-Start Hemodialysis.

BACKGROUNDChronic kidney disease (CKD) affects 10-15% of adult population worldwide. Incident patients on hemodialysis, mainly those on urgent-start dialysis at the emergency room, have a high mortality risk, which may reflect the absence of nephrology care. A lack of data exists regarding the influence of baseline factors on the mortality of these patients. The aim of this study was to evaluate the clinical and laboratory characteristics of this population and identify risk factors that contribute to their mortality.PATIENTS AND METHODSWe studied 424 patients who were admitted to our service between 01/2006 and 12/2012 and were followed for 1 year. We analyzed vascular access, risk factors linked to cardiovascular disease (CVD) and mineral and bone disease associated with CKD (CKD-MBD), and clinical events that occurred during the follow-up period. Factors that influenced patient survival were evaluated by Cox regression analysis.RESULTSThe patient mean age was 50 ± 18 years, and 58.7% of them were male. Hypertension was the main cause of primary CKD (31.8%). Major risk factors were smoking (19.6%), dyslipidemia (48.8%), and CVD (41%). Upon admission, most patients had no vascular access for hemodialysis (89.4%). Biochemical results showed that most patients were anemic with high C-reactive protein levels, hypocalcemia, hyperphosphatemia, elevated parathyroid hormone and decreased 25-hydroxy vitamin D. At the end of one year, 60 patients died (14.1%). These patients were significantly older, had a lower percentage of arteriovenous fistula in one year, and low levels of 25-hydroxy vitamin D.CONCLUSIONSThe combined evaluation of clinical and biochemical parameters and risk factors revealed that the mortality in urgent-start dialysis is associated with older age and low levels of vitamin D deficiency. A lack of a permanent hemodialysis access after one year was also a risk factor for mortality in this population

Predictive factors of one-year mortality in a cohort of patients undergoing urgent-start hemodialysis

Background Chronic kidney disease (CKD) affects 10-15% of adult population worldwide. Incident patients on hemodialysis, mainly those on urgent-start dialysis at the emergency room, have a high mortality risk, which may reflect the absence of nephrology care. A lack of data exists regarding the influence of baseline factors on the mortality of these patients. The aim of this study was to evaluate the clinical and laboratory characteristics of this population and identify risk factors that contribute to their mortality. Patients and methods We studied 424 patients who were admitted to our service between 01/2006 and 12/2012 and were followed for 1 year. We analyzed vascular access, risk factors linked to cardiovascular disease (CVD) and mineral and bone disease associated with CKD (CKD-MBD), and clinical events that occurred during the follow-up period. Factors that influenced patient survival were evaluated by Cox regression analysis. Results The patient mean age was 50 18 years, and 58.7% of them were male. Hypertension was the main cause of primary CKD (31.8%). Major risk factors were smoking (19.6%), dyslipidemia (48.8%), and CVD (41%). Upon admission, most patients had no vascular access for hemodialysis (89.4%). Biochemical results showed that most patients were anemic with high C-reactive protein levels, hypocalcemia, hyperphosphatemia, elevated parathyroid hormone and decreased 25-hydroxy vitamin D. At the end of one year, 60 patients died (14.1%). These patients were significantly older, had a lower percentage of arteriovenous fistula in one year, and low levels of 25-hydroxy vitamin D. Conclusions The combined evaluation of clinical and biochemical parameters and risk factors revealed that the mortality in urgent-start dialysis is associated with older age and low levels of vitamin D deficiency. A lack of a permanent hemodialysis access after one year was also a risk factor for mortality in this population121FUNDAÇÃO DE AMPARO À PESQUISA DO ESTADO DE SÃO PAULO - FAPESP2010/03867-

FGF-23 as a Predictor of Renal Outcome in Diabetic Nephropathy

Background and objectives Fibroblast growth factor 23 (FGF-23) has emerged as a new factor in mineral metabolism in chronic kidney disease (CKD). An important regulator of phosphorus homeostasis, FGF-23 has been shown to independently predict CKD progression in nondiabetic renal disease. We analyzed the relation between FGF-23 and renal outcome in diabetic nephropathy (DN). Design, setting, participants, & measurements DN patients participating in a clinical trial (enalapril+placebo versus enalapril+losartan) had baseline data collected and were followed until June 2009 or until the primary outcome was reached. Four patients were lost to follow-up. The composite primary outcome was defined as death, doubling of serum creatinine, and/or dialysis need. Results At baseline, serum FGF-23 showed a significant association with serum creatinine, intact parathyroid hormone, proteirturia, urinary fractional excretion of phosphate, male sex, and race. Interestingly, FGF-23 was not related to calcium, phosphorus, 25OH-vitamin D, or 24-hour urinary phosphorus. Mean follow-up time was 30.7 +/- 10 months. Cox regression showed that FGF-23 was an independent predictor of the primary outcome, even after adjustment for creatinine clearance and intact parathyroid hormone (10 pg/ml FGF-23 increase = hazard ratio, 1.09; 95% CI, 1.01 to 1.16, P = 0.02). Finally, Kaplan-Meier analysis showed a significantly higher risk of the primary outcome in patients with FGF-23 values of >70 pg/ml. Conclusions FGF-23 is a significant independent predictor of renal outcome in patients with macroalbuminuric DN. Further studies should clarify whether this relation is causal and whether FGF-23 should be a new therapeutic target for CKD prevention. Clin J Am Soc Nephrol 6: 241-247, 2011. doi: 10.2215/CJN.04250510FAPESP Fundacao de Amparo a Pesquisa do Estado de Sao Paul