Serum phosphate is associated with increased risk of bone fragility fractures in hemodialysis patients.

BACKGROUND: Bone fragility fractures are associated with high morbidity and mortality. This study analysed the association between the current biochemical parameters of CKD-MBD and bone fragility fractures in the COSMOS project. METHODS: COSMOS is a 3-year, multicentre, open cohort, prospective, observational study carried out in 6797 hemodialysis patients (227 centres from 20 European countries). The association of bone fragility fractures (outcome) with serum calcium, phosphate and PTH (exposure), was assessed using Standard Cox proportional hazards regression and Cox proportional hazards regression for recurrent events. Additional analyses were performed considering all-cause mortality as a competitive event for bone fragility fracture occurrence. Multivariable models were used in all strategies, with the fully adjusted model including a total of 24 variables. RESULTS: During a median follow-up of 24 months 252 (4%) patients experienced at least one bone fragility fracture (incident bone fragility fracture rate 28.5 per 1000 patient-years). In the fractured and non-fractured patients, the percentage of men was 43.7% and 61.4%, mean age 68.1 and 63.8 years and a haemodialysis vintage of 55.9 and 38.3 months respectively. Baseline serum phosphate > 6.1 mg/dL (reference value 4.3-6.1 mg/dL) was significantly associated with a higher bone fragility fracture risk in both regression models (HR: 1.53[95%CI: 1.10-2.13] and HR: 1.44[95%CI: 1.02-2.05]. The significant association persisted after competitive risk analysis (subHR: 1.42[95%CI: 1.02-1.98]) but the finding was not confirmed when serum phosphate was considered as a continuous variable. Baseline serum calcium showed no association with bone fragility fracture risk in any regression model. Baseline serum PTH > 800 pg/mL was significantly associated with a higher bone fragility fracture risk in both regression models, but the association disappeared after a competitive risk analysis. CONCLUSIONS: Hyperphosphatemia was independently and consistently associated with an increased bone fracture risk, suggesting serum phosphate could be a novel risk factor for bone fractures in hemodialysis patients.

Bone fractures and lumbar mineral density after renal transplantation. A long-term cross-sectional study.

BACKGROUND: The purpose of this work was to investigate the association of vertebral and peripheral fractures 10 yr after grafting with bone metabolic markers and body mass density (BMD). PATIENTS AND METHODS: One hundred thirty-eight recipients with stable graft function were included in a cross-sectional study. Graft function, biochemical mineral metabolism markers and body mass density (DEXA) were measured. Vertebral fractures were assessed by a semiquantitative analysis of lateral spine X-ray exam. RESULTS: At the time of the study, intact parathyroid hormone levels were 127.5 ± 78.4 pg/mL and serum calcidiol 20.4 ± 9.3 ng/mL. DEXA showed osteopenia in 47% and osteoporosis in 23% at lumbar spine, 51% and 14% at femoral neck, and 53% and 8% at trochanter. Eighty-five recipients presented vertebral fractures, 69 mild and 16 moderate/severe fractures. In the multivariate analysis, vertebral fractures were associated with older age (p = 0.010), length of follow-up (p = 0.022) and trochanter T-score (p = 0.038). Twenty-three patients presented peripheral fractures and 19 of them also had vertebral fractures. Patients with peripheral fractures were younger, mostly women and had lower BMD. CONCLUSIONS: Vertebral fractures were associated with lower BMD at trochanter. Most fractures were mild and were several times more frequent than in general population. Their clinical significance needs to be determined.

Comprehensive Cardiovascular and Renal Protection in Patients with Type 2 Diabetes.

Type 2 diabetes (T2DM) is one of the main public health care problems worldwide. It is associated with a marked increased risk of developing atherosclerotic vascular disease, heart failure, chronic kidney disease and death. It is essential to act during the early phases of the disease, through the intensification of lifestyle changes and the prescription of those drugs that have been shown to reduce these complications, with the aim not only of achieving an adequate metabolic control, but also a comprehensive vascular risk control. In this consensus document, developed by the different specialists that treat these patients (endocrinologists, primary care physicians, internists, nephrologists and cardiologists), a more appropriate approach in the management of patients with T2DM or its complications is provided. A particular focus is given to the global control of cardiovascular risk factors, the inclusion of weight within the therapeutic objectives, the education of patients, the deprescription of those drugs without cardiovascular benefit, and the inclusion of GLP-1 receptor agonists and SGLT2 inhibitors as cardiovascular protective drugs, at the same level as statins, acetylsalicylic acid, or renin angiotensin system inhibitors.

Are low levels of 25-hydroxyvitamin D a risk factor for cardiovascular diseases or malignancies in renal transplantation?

BACKGROUND: Observational studies in healthy people suggest an inverse relationship between 25-hydroxy-vitamin D (25(OH)D levels) and cardiovascular diseases and malignancies. We performed an observational prospective study in renal transplant recipients to investigate the effects of vitamin D deficiency on cardiovascular and malignancy risks. METHODS: From 389 renal transplant recipients, 331 with a functioning graft at 12 months were included in the study. Mineral metabolism parameters were measured at 1, 3, 4 and 12 months. Information regarding the cardiovascular events and malignancies were collected from an electronic database. RESULTS: According to the 1-year mean of 25(OH)D levels, 75 recipients (22.7%) had a normal vitamin D status, 161 (48.6%) had insufficiency and 95 (28.7%) had deficiency in vitamin D levels. During the follow-up, 80 recipients presented at least one cardiovascular event. The total cardiovascular diseases included: 27 patients with coronary diseases, 25 with cardiac failure, 18 with arrhythmia, 11 with acute cerebrovascular events and 19 with peripheral vascular disease. Cardiovascular events were not associated with 25(OH)D levels or vitamin D status, and the 10-year cumulative incidence was 29.3% for normal vitamin D status and 31.6% for insufficiency and 51.9% for deficiency (P = 0.216). Furthermore, Cox univariate analysis showed no association between cardiovascular events and vitamin D levels or vitamin D status. In addition, 53 recipients presented at least one malignancy: 33 non-melanoma skin malignancies and 20 non-skin malignancies (5 prostate, 3 kidney and urinary tract, 2 colon, 2 lung, 2 lymphoma, 2 breast and 4 from other locations). The cumulative incidence of malignancies was 21.3% for normal vitamin D status, 22.7% for insufficiency and 16.7% for deficiency (P = 0.818). CONCLUSIONS: Our data suggested that low vitamin D levels were not associated with an increased risk of cardiovascular diseases or malignancies. However, due to the small number of patients and events, the results should not be considered as definitive. Additional studies with a higher number of patients are required to elucidate the true impact of vitamin D status on cardiovascular and malignancy risks.

A retrospective study on outcome of microscopic polyangiitis in chronic renal replacement therapy.

BACKGROUND: Pauci-immune vasculitis is a heterogeneous disorder with an unfavourable prognosis. Renal involvement is frequently observed in antineutrophil cytoplasm autoantibody (ANCA)-associated small-vessel vasculitis and is an important cause of end-stage renal disease (ESRD). Renal replacement therapy (RRT) is frequently required. Although better prognosis under dialysis is well known, the long-term follow-up of pauci-immune renal vasculitis with RRT is rarely reported. METHODS: We described 24 patients with pauci-immune vasculitis and requirement of dialysis who were admitted in our institutions from January 1989 to December 2008. Mean age was 65 ± 12 years at the beginning of dialysis. There were 12 males and 12 females. Patients with Wegener's granulomatosis, Churg-Strauss syndrome or evidence of anti-glomerular basement membrane were excluded. The study group was formed by patients with a diagnosis of necrotizing extracapillary glomerulonephritis and microscopic polyangiitis. RESULTS: The distribution according to ANCAs was 14 p-ANCA (58%), 5 c-ANCA (21%) and 5 ANCA-negative (21%) pauci-immune renal vasculitis. Pulmonary renal syndrome (PRS) was observed in 10 patients at the onset of vasculitis. Corticosteroids and daily cyclophosphamide were administered to 18 patients, and one patient had intravenous cyclophosphamide. Five patients received isolated corticosteroid therapy. Early reduction in cyclophosphamide dosage was required in five patients due to leucopaenia. Mean follow-up after first dialysis was 89 ± 66 months (range 2-208). Twenty patients were included in haemodialysis (HD), and four patients were included in peritoneal dialysis (PD). At the end of the study, nine patients had received a cadaveric kidney transplant (KT). Relapses rate after the onset of dialysis was 0.03 episode/patient/year. PRS-associated relapses after beginning dialysis were observed in four patients. Main therapy in relapses was also corticosteroids and cyclophosphamide. Survival rates for year 1, 2 and 5 was 91%, 91% and 85%, respectively. Overall mortality at the end of the study was 31.8%. Five patients died in the PRS group, but only one death was associated with progressive pulmonary fibrosis. Higher mortality was observed in PRS vasculitis present at the onset of RRT (50% vs 16.7%, P = NS). Better outcome in patients who received a renal transplantation was observed (88.8% vs 53.8%, P = NS). Conclusions. Despite a low number of patients in this series, pauci-immune vasculitis prognosis under dialysis seems equal to other causes of chronic kidney disease. This study observed a low rate of relapses after beginning dialysis. Poor prognosis is related to severe complications at the beginning of RRT. Today, kidney transplantation is an important therapeutic option for these patients.

Optimizing the timing of nephrology referral for patients with diabetic kidney disease.

Age-standardized rates of diabetes mellitus (DM)-related complications, such as acute myocardial infarction, stroke or amputations, have decreased in recent years, but this was not associated with a clear reduction of the incidence of advanced chronic kidney disease (CKD) requiring renal replacement therapy. The early detection of diabetic kidney disease (DKD) is a key to reduce complications, morbidity and mortality. Consensus documents and clinical practice guidelines recommend referral of DM patients to nephrology when the estimated glomerular filtration rate falls below 30 mL/min/1.73 m2 or when albuminuria exceeds 300 mg/g urinary creatinine. Conceptually, it strikes as odd that patients with CKD are referred to the specialist caring for the prevention and treatment of CKD only when >70% of the functioning kidney mass has been lost. The increasing global health burden of CKD, driven in large part by DKD, the suboptimal impact of routine care on DKD outcomes as compared with other DM complications, the realization that successful therapy of CKD requires early diagnosis and intervention, the advances in earlier diagnosis of kidney injury and the recent availability of antidiabetic drugs with a renal mechanism of action and lack of hypoglycaemia risk, which additionally are cardio- and nephroprotective, all point towards a paradigm shift in the care for DM patients in which they should be referred earlier to nephrology as part of a coordinated and integrated care approach.

Salvage of accidentally sectioned peritoneal catheter: report of three cases.

Peritoneal dialysis (PD) accounts for 6% of patients on maintenance dialysis. There are several factors responsible for this low prevalence. Transfer of patients to hemodialysis when any problem in the technique is present is probably one of the most frequent reasons. Thus, when a problem in the PD catheter appears they are routinely removed instead of subjecting to salvage procedures. We report three cases of accidental cutting of the peritoneal catheter and present the steps taken to salvage the catheter without discontinuing the technique and avoiding withdrawal of the catheter.

[Evaluating renal function and indications for starting dialysis]. / Valoración de la función renal e indicaciones para el inicio de diálisis.

EVALUATION OF THE RENAL FUNCTION: For the follow-up of the graft renal function it must be measured the glomerular filtration rate by means of formulae that use the serum creatinine. The most used equation is the brief formula MDRD. - All patients transplanted must be included in the group of Renal Chronic Disease though the glomerular filtration rate is normal and there is no evidence of renal damage. - The measures of intervention proposed in the classification of the Renal Chronic Disease for its progressive establishment in the stage 1 to 3, must be applied to all the transplanted THE BEGINNING OF DIALYSIS: In spite of receiving attention of Nephrologists along the whole evolution, the patients with chronic dysfunction of the graft that need treatment with dialysis start later and with more uremic complications that the patients who start dialysis for the first time. - To change this trend, it is necessary to consider the treatment with dialysis when the glomerular filtration rate is lower than 15 ml/min/1,73 m2. If there appears any complication related to the uremia that cannot be handled by conservative treatment, the beginning of the dialysis is necessary. THE BEGINNING OF THE DIALYSIS OF PROGRAMMED FORM: The beginning of the dialysis of not programmed form in transplanted patients is difficult to justify if we take into account that such patients, have received nephrological attention along all their evolution. - To get a new vascular access in these patients can be difficult depending on the previous trombosis of arteriovenous fistulas. Therefore, it must be realized a prompt evaluation for de department of vascular surgery to guarantee a suitable vascular access. - As general norm, one must follow the same criterion advised for the not transplanted patient: the vascular access must be considered when the glomerular filtration rate is lower than 20 m/min/1,73 m2. - The patient who is going to be treated by dialysis peritoneal precise a very narrow follow-up to be able to programme the placement of the catheter peritoneal with a minimum of 15 days before beginning the training.

[Choosing the dialysis method for kidney transplant patients with advanced kidney disease]. / Elección de la modalidad de diálisis en la insuficiencia renal avanzada del paciente trasplantado renal.

The choice of the most of dialysis modality after renal graft loss is an unanswered question. Most patients start hemodialysis (HD) in this situation, because of several reasons: 1. In most dialysis programs HD predominates clearly over Peritoneal Dialysis (PD). 2. The star of dialysis in emergency situations makes the physician use HD 3. The fear of infections in case of maintenance of immunosupression to avoid immune response and to keep residual renal function in case of PD. A lot of patients could undergo PD in order to maintain the previous style of life, as an alternative in case of absence of vascular access and to avoid vascular accesses in children. Mortality seems to be greater in patients with graft loss than in those who start dialysis for the first time, although the comparison between both groups is methodologically difficult. However, there is no difference in mortality between patients who start HD and those who start PD. Studies comparing the rate of peritonitis in PD patients in both groups find controversial results. The analysis of the few, retrospective and biased studies which look for differences in patient survival in HD and DP suggests that prognosis of both groups is similar. The choice of dialysis modality must be similar to those patients which begin dialysis for the first time.

[Managing a failed kidney graft. Nephrectomy versus embolisation]. / Manejo del injerto renal fallido. Nefrectomía versus embolización.

The early diagnosis of the graft intolerance syndrome or a subclinical state of chronic inflammation due to a failed kidney allograft, is one of the goals that the nephrologists must fulfill to take a series of measures directed to solve this situation. Fever, haematuria, local pain and/or tenderness are the main clinical criteria to make a diagnosis. However, oftenly there are not any clinical symptoms and only the presence of parameters of chronic inflammation (elevated C-reactive protein, erythrocyte sedimentation rate, hypoalbuminemia and anemia resistant to erythropoietin therapy) are signs of this entity. Maintenance of immunosuppressive treatment is not advisable due to the risk of infections as well as the increase in cardiovascular risk (level evidence A). Transplantectomy is the best treatment if there are some associated complications such as allograft infection, neoplasia or high risk of graft rupture. However, surgical treatment is not exempt from risks and it is associated to a considerable rate of complications, with the consequent prolongation of the hospitalization stay. Therefore it is desirable to use less invasive procedures, such as embolization. This could be the first step unless the conditions enumerated in point 3 come up (Level evidence B). It is desirable to use prophylactic antibiotic before the embolization to avoid infectious complications (Level evidence B).

[Retransplant]. / Retrasplante.

Despite the advances in immunosuppressive therapy and in patient care, about 20-30% of patients will have lost their grafts after 3 years and this loss will continue by 3-4% per year. These patients are included in maintenance dialysis programmes and account for 4 to 10% of those admitted every year for maintenance dialysis therapy. Among those patients who loss their grafts 40-60% are included in transplant waiting lists. This increases the number of patients waiting for a graft and raises the dilemma about the rights to be included in deceased donor programmes. A common characteristic of these patients waiting for a second or even third transplant is the presence in the blood of antibodies to HLA antigens. A new transplant is the best therapeutic option for these patients, and the results are quite close to those achieved for the first graft. Moreover, a new transplant improves patient outcome when compared with those remaining in the waiting list. The best results are obtained in diabetic patients and in those between 18 to 50 years old (Evidence C). However, the percentage of patients retransplanted has not varied in the last years, possibly due to the wider criteria adopted on candidate selection that increases the waiting lists (Evidence B). In the second transplant, mismatched HLA-A,B antigens could be repeated if the recipient has not developed specific antibodies to these antigens. Recent cross-match has to be negative. Immunosuppressive therapy is similar to that used with first transplants. Lymphoproliferative diseases, BK virus nephropathy and primary glomerulonephritis do not preclude a second transplant (Evidence C).

Concentrated red grape juice exerts antioxidant, hypolipidemic, and antiinflammatory effects in both hemodialysis patients and healthy subjects.

BACKGROUND: Patients treated with hemodialysis frequently experience cardiovascular complications attributed, among other causes, to dyslipidemia, increased oxidative stress, and inflammation. OBJECTIVE: The aim of the study was to study the effects of dietary supplementation with concentrated red grape juice (RGJ), a source of polyphenols, on lipoprotein profile, antioxidant capacity, LDL oxidation, and inflammatory biomarkers. DESIGN: Twenty-six patients receiving hemodialysis and 15 healthy subjects were instructed to drink 100 mL RGJ/d for 14 d. Blood was drawn at baseline, twice during RGJ supplementation, and twice during the 6-mo follow-up period. As a control, 12 other randomly recruited hemodialysis patients not receiving RGJ were studied. Lipids, apolipoproteins, oxidized LDL, and antioxidant vitamins were measured in plasma. The bioavailability of RGJ polyphenols was assessed in healthy subjects. RESULTS: The maximum plasma concentration of quercetin was achieved 3 h after RGJ ingestion, which indicates that supplement-derived polyphenols are rapidly absorbed. In both healthy subjects and hemodialysis patients, RGJ consumption increased the antioxidant capacity of plasma without affecting concentrations of uric acid or ascorbic acid; reduced the concentration of oxidized LDL; and increased the concentration of cholesterol-standardized alpha-tocopherol. RGJ supplementation also caused a significant decrease in LDL-cholesterol and apolipoprotein B-100 concentrations, while increasing the concentrations of HDL cholesterol and apolipoprotein A-I. In a further study in hemodialysis patients, RGJ supplementation for 3 wk significantly reduced plasma monocyte chemoattractant protein 1, an inflammatory biomarker associated with cardiovascular disease risk. CONCLUSION: Dietary supplementation with concentrated RGJ improves the lipoprotein profile, reduces plasma concentrations of inflammatory biomarkers and oxidized LDL, and may favor a reduction in cardiovascular disease risk.

Lumbar bone mineral density in renal transplant patients on neoral and tacrolimus: a four-year prospective study.

BACKGROUND: This prospective study was designed to investigate the long-term evolution of bone mineral density (BMD) in kidney transplant recipients. METHODS: In 86 patients with functioning grafts, 65 on tacrolimus-based immunosuppression and 21 on cyclosporine-based immunosuppression, laboratory parameters and BMD measurements in lumbar spine (L2-L4) and femoral neck (FN) were performed by DEXA in the first month after transplantation (baseline) and yearly thereafter up to the fourth year. RESULTS: BMD did not change at 12 months in lumbar spine nor in the FN. Detailed analysis identified three patterns of BMD in lumbar spine at 12 months: BMD remained stable in 27 patients (31.4%), decreased >2% in 31 (36.0%) and increased >2% in 28 (32.6%). Patients with no change or gain presented a parallel increase of BMD in FN (P<0.001 in both groups). On multivariate analysis, the variables associated with no change or lumbar BMD loss were total prednisone dose in grams at 12 months (OR 1.402; 95% CI 1.038-1.893; P=0.028), calcitriol levels at 12 months (OR 0.936; 95% CI 0.892-0.982; P=0.007) and lumbar BMD at baseline (OR 1.006; 95% CI 1.002-1.010; P=0.002). Late treatment with calcium supplements and calcitriol did not improve osteopenia. CONCLUSIONS: One third of patients had bone loss mainly during the first year of follow-up. Bone loss was associated to higher baseline BMD, high steroid dose, and lower calcitriol levels at 1 year. Late administration of calcitriol and calcium supplements did not improve posttransplant osteopenia. More than 50% of patients were osteopenic 4 years after transplantation.

Choosing conservative therapy in chronic kidney disease.

INTRODUCTION: Incidence of use for various renal replacement therapies is well-known, but no data are available on conservative treatment use. OBJECTIVE: To assess the proportion of patients with chronic kidney failure receiving a conservative treatment. RESULTS: From July 1, 2013 to June 30, 2014, 232 patients with stage 5 CKD were seen in the Nephrology Department. After having received information on existing therapeutic options and having known the opinion of their treating physicians, 81 patients (35%) selected hemodialysis, 56 (24%) preferred peritoneal dialysis, 5 (2%) selected a preemptive transplant from a living donor, and in 90 (39%) a conservative treatment option was selected. In a univariate analysis using logistic regression, variables associated to a preference for conservative treatment were age, Charlson index excluding age, degree of walking difficulties, and functional dependence level, with the first three factors achieving statistical significance in a multivariate analysis. Presence of a severe disease resulting in a poor prognosis was the main reason for selecting a conservative treatment (49%), with the second one being patient refusal to receive a renal replacement therapy (26%). Mortality rate was 8.2/100 patient-months in conservative therapy group versus 0.6/100 patient-months in patients receiving renal replacement therapy (P<.001). In patients receiving conservative therapy, baseline glomerular filtration rate at the time of study enrollment was the sole variable showing a significant impact on survival. CONCLUSIONS: About 39% of patients with stage 5 CKD seen over a 1-year period in the Nephrology Department received conservative therapy. Age, co-morbidity, and functional disability were the factors associated to selecting a conservative therapy option.

Effects of a single, high oral dose of 25-hydroxycholecalciferol on the mineral metabolism markers in hemodialysis patients.

Vitamin D deficiency is common in dialysis patients with chronic kidney disease. Low levels have been associated with increased cardiovascular risk and mortality. We evaluated the administration of a high, single oral dose of 25-OH cholecalciferol (3 mg of Hidroferol, 180 000 IU) in patients on chronic hemodialysis. The 94 chronic hemodialysis patients with vitamin D deficiency 25 (OH)D <30 ng/mL included in the study were randomized into two groups. Follow-up time was 16 weeks. Neither the usual treatment for controlling Ca/P levels nor the dialysis bath (calcium of 2.5 mEq/L) were modified. Of the 86 patients who finished the study, 42 were in the treated group and 44 in the control group. An increase in 25(OH)D levels was observed in the treated group that persisted after 16 weeks and was associated with a significant decrease in parathyroid hormone (PTH) levels during the 8 weeks post-treatment. Baseline 1,25(OH)2 D levels of the treated group increased two weeks after treatment (5.9 vs. 21.9 pg/mL, P<0.001) but gradually reduced to 8.4 at week 16. The administration of a single 3 mg dose of 25-OH cholecalciferol seems safe in patients on hemodialysis and maintains sufficient levels of 25(OH)D with a decrease in PTH for 3 months.