Search

Background: Vitamin D deficiency is associated with increased risks of mortality in people with chronic kidney disease. The benefits and harm of vitamin D supplementation on cardiovascular outcomes and mortality are unknown. We aimed to assess the effectiveness of calcifediol in reducing mortality in patients with vitamin D insufficiency on hemodialysis compared to no additional therapy., Methods: A phase III, multicenter, randomized, open-label trial was conducted including 284 adults with vitamin D insufficiency undergoing hemodialysis who were randomly assigned to receive oral calcifediol or standard care for 24 months., Results: Two hundred eighty-four participants were enrolled (143 assigned to the calcifediol group and 141 to the no additional therapy group). The primary outcome (mortality) occurred in 34 and 31 participants in the calcifediol and control group, respectively [hazard ratio (HR) 1.03; 95% confidence interval (CI) 0.63-1.67]. Calcifediol had no detectable effects on cardiovascular death (HR 1.06; 95% CI 0.41-2.74), non-cardiovascular death (HR 1.13; 95% CI 0.62-2.04), nonfatal myocardial infarction (HR 0.20; 95% CI 0.02-1.67) or nonfatal stroke (HR could not be estimated). The incidence of hypercalcemia and hyperphosphatemia was similar between groups. None of the participants underwent parathyroidectomy., Conclusions: In adults treated with hemodialysis and who had vitamin D insufficiency, calcifediol supplementation for 24 months had inconclusive effects on mortality and cardiovascular outcomes., Trial Registration Number: NCT01457001., (© 2021. Italian Society of Nephrology.)

We herein report on a nationwide survey conducted in Italy to investigate the use of parathyroidectomy (PTX). In spite of the availability of newer and more effective drugs to control chronic kidney disease mineral bone disorder (CKD-MBD) biochemical abnormalities, PTX still remains a resource for nephrologists to use. However, observational analyses suggest that in recent years there has been a constant decline in the number of patients undergoing PTX. The reasons are not clear, though the increasing age and number of comorbidities of dialysis patients may partly explain this trend. Poor adherence to guidelines and/or geographical as well as logistic factors may also contribute to the lower use of PTX. The working group on CKD-MBD of the Italian Society of Nephrology launched a nationwide survey to investigate clinical practice patterns for PTX in Italy and identify modifiable factors that may limit accessibility to surgery.

Background: Parathyroid hormone (PTH) has been associated with anemia only in dialysis patients with severe hyperparathyroidism. Whether an association between PTH and hemoglobin also exists in patients with chronic kidney disease not on dialysis (CKD-patients) is still unclear. In this study we evaluated the association between PTH and hemoglobin in CKD-patients without severe secondary hyperparathyroidism., Methods: Hospitalized patients and outpatients (N = 979) were retrospectively evaluated and categorized according to PTH quartile and serum hemoglobin (<12.0, <11.0, <10.0 g/dl). Gender, diabetes, glomerular filtration rate (GFR), hemoglobin, PTH, markers of mineral metabolism, inflammation, iron status and nutrition were variables of adjustment in univariate and multivariate analysis., Results: An inverse association (p = 0.001) was observed between PTH and hemoglobin in patients as a whole, in diabetics, and in patients with GFR ≤60 ml/min. PTH was the single predictor of low hemoglobin in patients as a whole (unstandardized beta -2.12; p = 0.005), in diabetics (unstandardized beta -8.86; p = 0.007) and in patients with GFR ≤60 ml/min (unstandardized beta -2.52; p = 0.006). For each increase of quartile of PTH the risk of having hemoglobin level <10.0 mg/dl was more than doubled [hazard ratio (HR) 2.79, 95% confidence interval (CI) 2.00-3.88; p = 0.001]. The receiver operating characteristic curve showed that PTH ≥122 pg/ml had 67% sensitivity and 75% specificity in predicting hemoglobin level <10.0 g/dl with area under the curve of 0.758 (95% CI 0.73-0.78)., Conclusions: This study shows a significant inverse association between PTH and hemoglobin levels across the whole spectrum of non-dialysis CKD and a doubled risk of having serum hemoglobin <10.0 mg/dl in the absence of severely deranged PTH concentration. These findings may have clinical relevance in ascertaining the cause of unexplained low hemoglobin levels in CKD-patients.

Background: No study has evaluated the efficacy of non-calcium-containing phosphate binders in slowing progression of cardiac valve calcification or deterioration of kidney function in patients with chronic kidney disease not on dialysis. This study addressed these issues., Methods: Outpatients (n = 170) with stage 3-4 chronic kidney disease and either mitral or aortic valve calcification were evaluated in this single-center, single-arm, prospective observational study. Patients received sevelamer hydrochloride (1,600 mg/day) for 1 year. Cardiac valve calcification progression was assessed by echocardiography, and decline of renal function by estimated glomerular filtration rate. Parathyroid hormone, FGF-23 and C-reactive protein (CRP) serum concentration and urinary phosphorus excretion were assayed., Results: At the end of treatment with sevelamer (12th month), mitral valve calcification had decreased by 79.3% from baseline. At baseline, 69 patients had grade 1, 97 patients grade 2 and 4 patients grade 3 calcification scores; at the end of the study, 60 patients showed grade 1, and no mitral valve calcification was registered in the remaining patients. An aortic valve score of 1 was found in 32%, score of 2 in 58%, score of 3 in 9% and score of 4 in 1% of patients at baseline; at the end of the study, a score of 1 was found in 95% and a score of 2 in 5% of patients. Significant slowing down of renal function decline (p<0.001), reduction of FGF-23 and CRP concentration (p<0.0001) and phosphorus excretion (p<0.0001) were observed., Conclusions: One-year treatment with a non-calcium-containing phosphate binder may hamper the progression of cardiac valve calcification and slow the decline of renal function, as well as reduce serum concentration of FGF-23 and CRP and urinary phosphorus excretion.

Background: Hemodialysis patients have a high cardiovascular mortality, and hypertension is the most prevalent treatable risk factor. We aimed to assess the predictive significance of dialysis-to-dialysis variability in blood pressure in hemodialysis patients., Methods: We performed a historical cohort study in 1,088 prevalent hemodialysis patients, followed up for 5 years. The risk of cardiovascular death was determined in relation to dialysis-to-dialysis variability in blood pressure, maximum blood pressure and pulse pressure., Results: Variability in blood pressure was a predictor of cardiovascular death (hazard ratio [HR] = 1.242; 95% confidence interval [95% CI], 1.004-1.537; p=0.046). Also age (HR=1.021; 95% CI, 1.011-1.048; p=0.049), diabetes (HR=1.134; 95% CI, 1.128-1.451; p=0.035), creatinine (HR=0.837; 95% CI, 0.717-0.977; p=0.024) and albumin (HR=0.901; 95% CI, 0.821-0.924; p=0.022) influenced mortality. Maximum blood pressure and pulse pressure did not show any effect on cardiovascular death., Conclusion: Dialysis-to-dialysis variability in blood pressure is a predictor of cardiovascular mortality in hemodialysis patients, and blood pressure variability may be used in managing hypertension and predicting outcomes in dialysis patients.

Familial lecithin:cholesterol acyltransferase (LCAT) deficiency is an autosomal recessive disorder of lipoprotein metabolism, resulting from loss of function of lecithin:cholesterol acyltransferase (LCAT; EC 2.3.1.43), a key enzyme in extracellular cholesterol metabolism and reverse cholesterol transport (RCT). The human LCAT gene has been mapped to chromosome band 16q22, and consists of 6 exons encoding for a mature protein of 416 amino acids. In the present study, we describe the molecular phenotype of a patient with classical LCAT deficiency and progressive renal failure. Sequence analysis of the LCAT gene showed 2 homozygous missense mutations: the common variant p.S208T, described as a homozygous change for the first time, and a missense mutation characterized by the substitution of Leu372 to Arg. Clinical, biochemical and renal histological studies were also performed to elucidate the functional effects of these variations. In the proband and his brother, LCAT activity and plasma cholesterol esterification rate (CER) were absent, while plasma LCAT concentrations were slightly reduced. By light microscopy, silver-stained renal biopsy specimens of the proband showed focal segmental glomerulosclerosis, while electron microscopy detected lipid deposits with both vacuolar lucent appearance and electron-dense lamellar structures within the mesangial matrix and glomerular basement membrane. This study describes for the first time the occurrence of two homozygous missense mutations as the common variant p.S208T and the mutation p.L372R in familial LCAT deficiency.

Many studies have shown how gene mutations and genetic polymorphisms could influence secondary uremic hyperparathyroidism (HPTH), modulating parathyroid (PT) function and hyperplasia. Parathyroid hormone (PTH) gene expression and hormone secretion is regulated mainly by serum calcium, with a post-transcriptional effect, and by vitamin D with a transcriptional effect. PT cells retain the ability to proliferate and to apoptose. Hyperphosphatemia, hypocalcemia and vitamin D deficiency all stimulate PT cell proliferation. In the early stage of chronic uremia, PT proliferation is polyclonal, as in diffuse hyperplasia, whereas nodular hyperplasia growth is monoclonal with an increasingly recognized genetic background. HPTH has been associated with a number of familial diseases, such as multiple endocrine neoplasia-type 1 (MEN1), multiple endocrine neoplasia-type2A (MEN2A), neurofibromatosis type1 (NF1) and HPTH with multiple ossifying jaw fibromas (HPT-JT Syndrome). The genes involved in these diseases have been also investigated in secondary HPTH (sHPTH). Moreover, in sporadic and secondary uremic HPTH, clonal rearrangement and/or oncogene overexpression, gene deletions and tumor suppressor gene inactivation have been reported. However, each condition shows different patterns of genetic abnormalities. Finally, PT function modulation by genetic polymorphisms of vitamin D and calcium receptors and of the PTH gene is reviewed.