Circulatory Imbalance of Essential and Toxic Trace Elements in Pre-dialysis and Hemodialysis Patients.

The status of essential and toxic trace elements in patients with different stages of chronic kidney disease (CKD) is still unclear and not well characterized. The present study examined the circulatory levels of a wide panel of trace elements (Al, Cr, Mn, Co, Ni, Cu, Zn, As, Se, Rb, Sr, Cd, Pb, and U) in hemodialysis patients (HD group) and pre-dialysis patients with stage 3 CKD (PD group). Comparisons were made between groups of patients and healthy individuals from the control group (CG). The levels of Al, Mn, Co, Ni, Cu, As, Se, Sr, and Pb were higher, while the levels of Cr, Zn, Rb, Cd, and U were lower in HD patients than in our CG. Higher levels of Al and Se, as well as lower levels of As, Sr, Zn, Rb, and U were significant and distinguished HD from PD. Among other analyzed elements, Co, Se, and U are the only trace elements that did not distinguish PD from CG at a statistically significant level. The HD group had lower serum U levels than the PD group, and this could be a result of hemodialysis. This study also revealed that the Cu/Zn ratio could be used as a marker for early and late detection of renal failure. Marked changes of essential and toxic trace element levels in sera indicate additional pathophysiological events in CKD, which could additionally contribute to the preexisting increased morbidity of HD patients. Measurement of trace elements in HD patients should be performed routinely.

Sclerostin and DKK1 circulating levels associate with low bone turnover in patients with chronic kidney disease Stages 3 and 4.

BACKGROUND: Disordered mineral and bone metabolism is a common complication of chronic kidney disease (CKD). Bone biopsy remains the gold standard tool for evaluating renal osteodystrophy (ROD), but it is an invasive procedure. Despite a growing interest in the ability of newer bone biomarkers to discriminate between different forms of ROD, data on pre-dialysis patients are scarce. METHODS: A cross-sectional study was conducted in a cohort of 56 patients with CKD Stages 3 and 4. Participants underwent a transiliac bone biopsy after a course of double tetracycline labelling. Circulating levels of Wnt signalling inhibitors sclerostin and Dickkopf-1 (DKK1), soluble receptor activator of nuclear factor-κB ligand (sRANKL) and osteoprotegerin were measured and correlated with histomorphometric analysis results. RESULTS: Most patients had abnormal bone histology and low-turnover bone disease was the predominant form of ROD. Characteristics associated with high bone turnover were worse renal function, lower serum calcium and higher intact parathyroid hormone and fibroblast growth factor-23 levels. Patients with low bone turnover, on the other hand, presented with higher sclerostin along with lower DKK1 and sRANKL levels. In the multivariable logistic regression analysis, sclerostin and DKK1 levels were independently associated with low-turnover bone disease. CONCLUSIONS: Our results suggest that circulating levels of Wnt signalling inhibitors sclerostin and DKK1 are predictive of low-turnover bone disease in patients not yet on dialysis. Further research is needed to assess the performance of these bone turnover biomarkers, compared with histomorphometric analysis, in the diagnosis and treatment monitoring of ROD.

Efficacy and safety of calcium carbonate in normophosphataemic patients with chronic kidney disease Stages 3 and 4.

BACKGROUND: Disordered bone and mineral metabolism are a common complication of chronic kidney disease (CKD). Phosphate binders are often prescribed in advanced CKD, when hyperphosphataemia develops. Little is known about the role of these drugs in earlier stages, when serum phosphorus levels are kept in the normal range by increased urinary excretion. METHODS: A retrospective, controlled observational study was conducted on a cohort of 78 pre-dialysis patients. Subjects had CKD Stage 3 or 4, normal serum phosphorus levels and increased urinary fractional excretion of phosphate. Thirty-eight patients receiving calcium carbonate for 24 months were compared with 40 patients under no phosphate binders, regarding mineral metabolism parameters and vascular calcification scores. RESULTS: Calcium carbonate decreased mean urinary fractional excretion of phosphate and median 24-h urine phosphorus, whereas no significant change was seen in the control group. Mean serum phosphorus and median serum intact parathyroid hormone (iPTH) remained stable in treated patients but increased in the control group. Vascular calcification, assessed by Kauppila and Adragão scores, worsened under calcium carbonate with no significant change in the control group. CONCLUSIONS: Calcium carbonate reduced urinary phosphate excretion and prevented the rise in phosphorus and iPTH serum levels in a cohort of normophosphataemic pre-dialysis patients. However, treatment was associated with increased vascular calcification, suggesting that calcium-based phosphate binders are not a safe option for CKD patients.

Balancing the Covid-19-motivated vascular access guidelines and patient-centred care of pre-dialysis candidates.

The recommendations recently proposed by the European and American Vascular Societies in this new 'Covid-19' era regarding the triage of various vascular operations into urgent, emergent and programmed based on the nature of their pathology aim at reserving health care expenses and hospital staff towards managing the current unexpected worldwide pandemic to the highest possible degree. The suggestion for implementation of these changes into real-world practice, however, does not come without a cost. In particular, the recommendation for deferral of access creation in pre-dialysis patients, ethical, socio-economic and medico-legal issues arise which should be seriously taken into consideration. At the end of the day, vascular access creation is the lifeline of haemodialysis patients and the indication for surgery warrants patient-specific clinical judgement rather than 'group labelling'.

Differences in Risk Factors and Prevalence of Vascular Calcification between Pre-Dialysis and Hemodialysis Balkan Nephropathy Patients.

Aims: The aim of this study was to compare the risk factors and prevalence of vascular calcification (VC) in pre-dialysis and hemodialysis (HD) patients with Balkan endemic nephropathy (BEN) or other kidney diseases (non-BEN). Materials and Methods: The study involved 115 patients, 32 pre-dialysis and 83 HD patients, separated into groups of BEN and non-BEN patients. In addition to interviews, objective examinations and laboratory analyses, VC was assessed using Adragao score. Results: Patients with BEN were significantly older in both groups, while pre-dialysis BEN patients had significantly lower systolic blood pressure, serum cholesterol and phosphorus levels, but higher urinary excretion of phosphorus than non-BEN patients. These differences were lost in HD groups. In pre-dialysis patients, prevalence of VC was lower in BEN than in non-BEN group and mean VC score differed significantly between them (2.8 (1.7) vs. 4.6 (1.8); p = 0.009). No significant difference in VC score was found between BEN and non-BEN patients on HD. Multivariate analysis showed that in pre-dialysis patients VC score >4 was associated with lower iPTH and higher serum cholesterol level, but in the HD group with higher serum triglyceride level and longer HD vintage. Conclusions: Lower prevalence of risk factors for VC in the BEN than non-BEN patients was found in pre-dialysis but not in HD group and this was reflected in the prevalence and severity of VC in the groups. Prevalence of VC and mean VC score were significantly lower in pre-dialysis BEN than in non-BEN patients but not for those on HD.

Effects of Cardiovascular Events on End-Stage Renal Disease and Mortality in Patients With Chronic Kidney Disease Before Dialysis.

Cardiovascular events (CVEs) are major complications in patients with chronic kidney disease (CKD). However, few studies have investigated the effects of CVEs on end-stage renal disease (ESRD) and mortality of pre-dialysis patients. We followed 377 CKD patients who were at stage ≥G3 at first clinic visit in the Shuuwa General Hospital between April 2005 and July 2014. After taking baseline patient data, we evaluated renal survival rates and all-cause and CVE-related mortality in patients with CVEs [(+)CVEs] and without CVEs [(-)CVEs]. A total of 99 CVEs occurred in 93 study patients (57.0% cardiac events, 43.0% cerebrovascular events, and 6.5% peripheral artery disease events). During the study period, 127 patients reached ESRD over a median of 4.51 years' follow-up. Kaplan-Meier analysis found longer renal survival rates in the (-)CVEs group compared with the (+)CVEs group. Forty patients died during the study period over a median of 5.43 years' follow-up. Survival rates for all-cause and CVE-related mortality of (-)CVEs patients were higher than in (+)CVEs patients. After adjustment for sex, age, current smoking, blood pressure, diabetes, estimated glomerular filtration rate, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, left ventricular hypertrophy, body mass index, albumin, hemoglobin, calcium, phosphate, C-reactive protein, and spot urine protein, the occurrence of CVEs was still a significant risk factor for ESRD (HR 1.516, P = 0.017) and all-cause mortality (HR 7.871, P < 0.001). Our findings suggest that the occurrence of CVEs is a potent risk factor for ESRD and mortality in CKD patients before dialysis.

Efficacy of erythropoietin in renal function of pre-dialysis patients with chronic renal failure / 대한내과학회지

BACKGROUND: Anemia is one of the most important risk factors for cardiovascular morbidity and mortality in patients with chronic renal failure. The most effective treatment modality for anemia is erythropoietin injection. Besides erythropoietic effect, erythropoietin has multiple beneficial effects such as anti-oxidant, anti-hypoxic, anti-apoptotic and vasculogenetic effects, and prevents tubular lesions and interstitial fibrosis. Despite lots of advantages of erythropoietin therapy, the number of patients treated with this agent is modest, particularly during the pre-dialysis chronic renal failure. We conducted a clinical trial to evaluate the effects of erythropoietin on renal function in the anemic pre-dialysis patients with chronic renal failure. METHODS: Data of 23 pre-dialysis patients with chronic renal failure were analyzed retrospectively 6 months prior, and prospectively 6 months after the initiation of erythropoietin therapy. Erythropoietin was admitted at a dose of 3000 IU weekly with supplementary iron. RESULTS: The average hematocrit and hemoglobin rose from 22.1+/-2.5%, 7.4+/-0.8 g/dL to 28.4+/-4.2%, 9.6+/-1.5 g/dL, respectively. When linear regression analysis was applied to pre- and post-erythropoietin glomerular filtration rate and 1/Cr, mean rate of decline of glomerular filtration rate were significantly delayed (p=0.039) but that of 1/Cr had a tendency to be delayed but was not statistically meaningful (p=0.099). CONCLUSIONS: Treatment of the anemia with low dose erythropoietin in pre-dialysis patients with chronic renal failure is relatively safe and may slow the rate of renal function deterioration.