Although rare, hereditary diseases, such as autosomal dominant polycystic kidney disease (ADPKD) and Fabry disease (FD) may significantly progress towards severe nephropathy. It is crucial to ...characterize it accurately, predict the course of the illness and estimate treatment effectiveness. A huge effort has been undertaken to find reliable biomarkers that might be useful for an early prevention of the disease progression and/or any invasive diagnostic procedures. The study of proteomics, or the small peptide composition of a sample, is a field of study under continuous development. Over the past years, several strategies have been created to study and define the proteome of samples from widely varying origins. However, urinary proteomics has become essential for discovering novel biomarkers in kidney disease. Here, the extracellular vesicles in human urine that contain cell-specific marker proteins from every segment of the nephron, offer a source of potentially valuable urinary biomarkers, and may play an essential role in kidney development and kidney disease. This review summarizes the relevant literature investigating the proteomic approaches and potential applications in the regular studies of ADPKD and FD.
Background. Lanthanum carbonate (LC) has been proposed as a new phosphate binder. Presented here are the results from one centre that participated in a multicentre trial to assess the effect of ...treatment with LC and calcium carbonate (CC) on the evolution of renal osteodystrophy in dialysis patients. Bone biopsies were performed at baseline, after 1 year of treatment and after a further 2-year follow-up period to assess the lanthanum concentration in bone and plasma. Methods. Twenty new dialysis patients were randomized to receive LC (median dose 1250 mg) for 1 year (n = 10), followed by 2 years of CC treatment or CC (n = 10) during the whole study period (3 years). Results. After 36 weeks of treatment, steady state was reached with plasma lanthanum levels varying around 0.6 ng/ml. Six weeks after cessation of 1 year of treatment, the plasma lanthanum levels declined to a value of 0.17 ± 0.12 ng/ml (P < 0.05) and after 2 years to 0.09 ± 0.03 ng/ml. Plasma and bone lanthanum levels did not correlate with the average lanthanum dose at any time point. The mean bone concentration in patients receiving LC increased from 0.05 ± 0.03 to 2.3 ± 1.6 µg/g (P < 0.05) after 1 year and slightly decreased at the end of the study to 1.9 ± 1.6 µg/g (P < 0.05). Conclusions. Bone deposition after 1 year of treatment with LC is low (highest concentration: 5.5 µg/g). There is a slow release of lanthanum from its bone deposits 2 years after the discontinuation of the treatment and no association with aluminium-like bone toxicity.
Several microRNAs (miRNAs) have been linked to chronic kidney disease (CKD) mortality, cardiovascular (CV) complications and kidney disease progression. However, their association with clinical ...outcomes remains poorly evaluated. We used real-time qPCR to measure serum levels of miR-126 and miR-223 in a large cohort of 601 CKD patients (CKD stage G1 to G5 patients or on renal replacement therapy - CKD G5D) from Ghent University Hospital and 31 healthy controls. All-cause mortality and cardiovascular and renal events were registered as endpoints over a 6 year follow-up period. miR-126 levels were significantly lower from CKD stage G2 on, compared to controls. The serum levels of miR-223 were significantly lower from CKD stage G3B on. When considering overall mortality, patients with levels of either miR-126 or miR-223 below the median had a lower survival rate. Similar results were observed for CV and renal events. The observed link between the two miRNAs' seric levels and mortality, cardiovascular events or renal events in CKD appears to depend on eGFR. However, this does not preclude their potential role in the pathophysiology of CKD. In conclusion, CKD is associated with a decrease in circulating miR-223 and miR-126 levels.
Acute kidney injury (AKI) increases the risk of death in acute ischemic stroke (AIS) patients. Intravenous thrombolytic therapy (iv. rt-PA) seems to be the most effective treatment for AIS patients. ...The effects of AKI on iv. rt-PA treated AIS cases is less studied. Our paper addresses this issue.
45 consecutive stroke patients treated with iv. rt-PA (median age = 64 years; 29 male) and 59 age and sex matched controls not eligible for iv. rt-PA have been enrolled in our study. Subjects were followed-up until hospital release or death (median follow up time = 12 days).
The prevalence of AKI did not differ between iv. rt-PA treated patients and controls (35.5% vs. 33.89%). In both groups, AKI was associated with increased in-hospital mortality: 50.0% vs. 3.4% p<0.0001 (in the rt-PA treated), and 45% vs. 30.7% (in controls). AKI iv. rt-PA treated patients had a significantly higher risk of in hospital mortality as compared to the no-AKI iv. rt-PA treated (HR = 15.2 (95%CI 1.87 to 124.24; P = 0.011). In a Cox-multivariate model, the presence of AKI after iv. rt-PA remained a significant factor (HR = 8.354; p = 0.041) influencing the in-hospital mortality even after correction for other confounding factors. The independent predictors for AKI were: decreased eGFR baseline and elevated serum levels of uric acid at admission, (the model explained 60.2% of the AKI development).
The risk of AKI was increased in AIS patients. Thrombolysis itself did not increase the risk of AKI. In the iv. rt-PA patients, as compared to non-AKI, those which developed AKI had a higher rate of in-hospital mortality. The baseline eGFR and the serum uric acid at admission were independent predictors for AKI development in the iv. rt-PA treated AIS patients.
Proteome analysis of complex biological samples for biomarker identification remains challenging, among others due to the extended range of protein concentrations. High-abundance proteins like ...albumin or IgG of plasma and urine, may interfere with the detection of potential disease biomarkers. Currently, several options are available for the depletion of abundant proteins in plasma. However, the applicability of these methods in urine has not been thoroughly investigated. In this study, we compared different, commercially available immunodepletion and ion-exchange based approaches on urine samples from both healthy subjects and CKD patients, for their reproducibility and efficiency in protein depletion. A starting urine volume of 500 μL was used to simulate conditions of a multi-institutional biomarker discovery study. All depletion approaches showed satisfactory reproducibility (n=5) in protein identification as well as protein abundance. Comparison of the depletion efficiency between the unfractionated and fractionated samples and the different depletion strategies, showed efficient depletion in all cases, with the exception of the ion-exchange kit. The depletion efficiency was found slightly higher in normal than in CKD samples and normal samples yielded more protein identifications than CKD samples when using both initial as well as corresponding depleted fractions. Along these lines, decrease in the amount of albumin and other targets as applicable, following depletion, was observed. Nevertheless, these depletion strategies did not yield a higher number of identifications in neither the urine from normal nor CKD patients. Collectively, when analyzing urine in the context of CKD biomarker identification, no added value of depletion strategies can be observed and analysis of unfractionated starting urine appears to be preferable.
Fibroblast growth factor-23 (FGF23) appears to be one of the most promising biomarkers and predictors of cardiovascular risk in patients with heart disease and normal kidney function, but moreover in ...those with chronic kidney disease (CKD). This review summarizes the current knowledge of FGF23 mechanisms of action in the myocardium in the physiological and pathophysiological state of CKD, as well as its cross-talk to other important signaling pathways in cardiomyocytes. In this regard, current therapeutic possibilities and future perspectives are also discussed.
Abstract
Background
Publications from the last decade have increased knowledge regarding long-term risks after kidney donation. We wanted to perform a survey to assess how transplant professionals in ...Europe inform potential kidney donors regarding long-term risks. The objectives of the survey were to determine how they inform donors and to what extent, and to evaluate the degree of variation.
Methods
All transplant professionals involved in the evaluation process were considered eligible, regardless of the type of profession. The survey was dispatched as a link to a web-based survey. The subjects included questions on demographics, the information policy of the respondent and the use of risk calculators, including the difference of relative and absolute risks and how the respondents themselves understood these risks.
Results
The main finding was a large variation in how often different long-term risks were discussed with the potential donors, i.e. from always to never. Eighty percent of respondents stated that they always discuss the risk of end-stage renal disease, while 56% of respondents stated that they always discuss the risk of preeclampsia. Twenty percent of respondents answered correctly regarding the relationship between absolute and relative risks for rare outcomes.
Conclusions
The use of written information and checklists should be encouraged. This may improve standardization regarding the information provided to potential living kidney donors in Europe. There is a need for information and education among European transplant professionals regarding long-term risks after kidney donation and how to interpret and present these risks.
A multicenter study on the affects of lanthanum carbonate (Fosrenol™) and calcium carbonate on renal bone disease in dialysis patients.
Lanthanum carbonate (LC) (Fosrenol™) is a novel new treatment ...for hyperphosphatemia. In this phase III, open-label study, we compared the effects of LC and calcium carbonate (CC) on the evolution of renal osteodystrophy (ROD) in dialysis patients.
Ninety-eight patients were randomized to LC (N = 49) or CC (N = 49). Bone biopsies were taken at baseline and after one year of treatment. Acceptable paired biopsies were available for static and dynamic histomorphometry studies in 33 LC and 30CC patients. Blood samples were taken at regular intervals for biochemical analysis and adverse events were monitored.
LC was well tolerated and serum phosphate levels were well controlled in both treatment groups. The incidence of hypercalcemia was lower in the LC group (6% vs. 49% for CC). At baseline, subtypes of ROD were similarly distributed in both groups, with mixed ROD being most common. At one-year follow-up in the LC group, 5 of 7 patients with baseline low bone turnover (either adynamic bone or osteomalacia), and 4 of 5 patients with baseline hyperparathyroidism, had evolved toward a normalization of their bone turnover. Only one lanthanum-treated patient evolved toward adynamic bone compared with 6 patients in the CC group. In the LC group, the number of patients having either adynamic bone, osteomalacia, or hyperpara decreased overall from 12 (36%) at baseline to 6 (18%), while in the calcium group, the number of patients with these types of ROD increased from 13 (43%) to 16 (53%).
LC is a poorly absorbed, well-tolerated, and efficient phosphate binder. LC-treated dialysis patients show almost no evolution toward low bone turnover over one year (unlike CC-treated patients), nor do they experience any aluminum-like effects on bone.
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