How to routinely collect data on patient-reported outcome and experience measures in renal registries in Europe: an expert consensus meeting

Despite the potential for patient-reported outcome measures (PROMs) and experience measures (PREMs) to enhance understanding of patient experiences and outcomes they have not, to date, been widely incorporated into renal registry datasets. This report summarizes the main points learned from an ERA-EDTA QUEST-funded consensus meeting on how to routinely collect PROMs and PREMs in renal registries in Europe. In preparation for the meeting, we surveyed all European renal registries to establish current or planned efforts to collect PROMs/PREMs. A systematic review of the literature was performed. Publications reporting barriers and/or facilitators to PROMs/PREMs collection by registries were identified and a narrative synthesis undertaken. A group of renal registry representatives, PROMs/PREMs experts and patient representatives then met to (i) share any experience renal registries in Europe have in this area; (ii) establish how patient-reported data might be collected by understanding how registries currently collect routine data and how patient-reported data is collected in other settings; (iii) harmonize the future collection of patient-reported data by renal registries in Europe by agreeing upon preferred instruments and (iv) to identify the barriers to routine collection of patient-reported data in renal registries in Europe. In total, 23 of the 45 European renal registries responded to the survey. Two reported experience in collecting PROMs and three stated that they were actively exploring ways to do so. The systematic review identified 157 potentially relevant articles of which 9 met the inclusion criteria and were analysed for barriers and facilitators to routine PROM/PREM collection. Thirteen themes were identified and mapped to a three-stage framework around establishing the need, setting up and maintaining the routine collection of PROMs/PREMs. At the consensus meeting some PROMs instruments were agreed for routine renal registry collection (the generic SF-12, the disease-specific KDQOL™-36 and EQ-5D-5L to be able to derive quality-adjusted life years), but further work was felt to be needed before recommending PREMs. Routinely collecting PROMs and PREMs in renal registries is important if we are to better understand what matters to patients but it is likely to be challenging; close international collaboration will be beneficial

Selenium-containing amino acids are targets for myeloperoxidase-derived hypothiocyanous acid: determination of absolute rate constants and implications for biological damage

Elevated MPO (myeloperoxidase) levels are associated with multiple human inflammatory pathologies. MPO catalyses the oxidation of Cl−, Br− and SCN− by H2O2 to generate the powerful oxidants hypochlorous acid (HOCl), hypobromous acid (HOBr) and hypothiocyanous acid (HOSCN) respectively. These species are antibacterial agents, but misplaced or excessive production is implicated in tissue damage at sites of inflammation. Unlike HOCl and HOBr, which react with multiple targets, HOSCN targets cysteine residues with considerable selectivity. In the light of this reactivity, we hypothesized that Sec (selenocysteine) residues should also be rapidly oxidized by HOSCN, as selenium atoms are better nucleophiles than sulfur. Such oxidation might inactivate critical Sec-containing cellular protective enzymes such as GPx (glutathione peroxidase) and TrxR (thioredoxin reductase). Stopped-flow kinetic studies indicate that seleno-compounds react rapidly with HOSCN with rate constants, k, in the range 2.8×103–5.8×106 M−1·s−1 (for selenomethionine and selenocystamine respectively). These values are ~6000-fold higher than the corresponding values for H2O2, and are also considerably larger than for the reaction of HOSCN with thiols (16-fold for cysteine and 80-fold for selenocystamine). Enzyme studies indicate that GPx and TrxR, but not glutathione reductase, are inactivated by HOSCN in a concentration-dependent manner; k for GPx has been determined as ~5×105 M−1·s−1. Decomposed HOSCN did not induce inactivation. These data indicate that selenocysteine residues are oxidized rapidly by HOSCN, with this resulting in the inhibition of the critical intracellular Sec-dependent protective enzymes GPx and TrxR

Oxidative protein labeling in mass-spectrometry-based proteomics

Oxidation of proteins and peptides is a common phenomenon, and can be employed as a labeling technique for mass-spectrometry-based proteomics. Nonspecific oxidative labeling methods can modify almost any amino acid residue in a protein or only surface-exposed regions. Specific agents may label reactive functional groups in amino acids, primarily cysteine, methionine, tyrosine, and tryptophan. Nonspecific radical intermediates (reactive oxygen, nitrogen, or halogen species) can be produced by chemical, photochemical, electrochemical, or enzymatic methods. More targeted oxidation can be achieved by chemical reagents but also by direct electrochemical oxidation, which opens the way to instrumental labeling methods. Oxidative labeling of amino acids in the context of liquid chromatography(LC)–mass spectrometry (MS) based proteomics allows for differential LC separation, improved MS ionization, and label-specific fragmentation and detection. Oxidation of proteins can create new reactive groups which are useful for secondary, more conventional derivatization reactions with, e.g., fluorescent labels. This review summarizes reactions of oxidizing agents with peptides and proteins, the corresponding methodologies and instrumentation, and the major, innovative applications of oxidative protein labeling described in selected literature from the last decade

Glomerular filtration rate-estimating equations for patients with advanced chronic kidney disease

Renal function is often estimated using one of several glomerular filtration rate (GFR) estimating equations. However, there is no consensus which estimating equation performs best in patients with advanced renal failure. We compared the performance of five different estimated GFR (eGFR) equations [Cockcroft-Gault, Modification of Diet in Renal Disease (MDRD), Chronic Kidney Disease (CKD) Epidemiology collaboration (CKD-EPI) and Mayo Clinic and Lund-Malm] with measured GFR (plasma iohexol clearance) in 2098 referred CKD patients with mGFR 30 mL/min/1.73 m(2). There were 398 patients with an mGFR 10 mL/min/1.73 m(2), 1974 with a measured GFR (mGFR) 1120 mL/min/1.73 m(2) and 749 patients with mGFR 2130 mL/min/1.73 m(2). Across the entire range, the median bias of eGFR was lowest for the Lund-Malm equation (0.7 mL/min/1.73 m(2)), followed by the CKD-EPI (1.2 mL/min/1.73 m(2)), the MDRD (1.6 mL/min/1.73 m(2)), Mayo Clinic equation (1.7 mL/min/1.73 m(2)) and Cockcroft-Gault equation (4.6 mL/min/1.73 m(2)). The best accuracy within 30 of mGFR was also for Lund-Malm (76), while it was similar for CKD-EPI, MDRD and Mayo (6567). The Cockcroft-Gault had the worst accuracy of only 54.The median bias was stable across mGFR categories, while the accuracy within 30 of mGFR became worse with decreasing mGFR. All equations performed best among patients with hereditary kidney diseases and tubulointerstitial disease. Accuracy was generally worse for patients 65 years of age and for those with diabetic nephropathy. In patients with advanced renal failure, the GFR-estimating equations show reasonably good performance on the population level. On the individual patient level, they are inaccurate, especially in elderly patients and those with diabetic nephropathy

Incidence and risk factors for hip or other bone fractures among hemodialysis patients in the Dialysis Outcomes and Practice Patterns Study.

The available data on bone fractures in hemodialysis (HD) patients are limited to results of a few studies of subgroups of patients in the United States. This study describes the prevalence of hip fractures and the incidence and risk factors associated with hip and other fractures in representative groups of HD facilities (n=320) and patients (n=12 782) from the 12 countries in the second phase of the Dialysis Outcomes and Practice Patterns Study (2002-2004). Among prevalent patients, 2.6% had a prior hip fracture. The incidence of fractures was 8.9 per 1000 patient years for new hip fractures and 25.6 per 1000 for any new fracture. Older age (relative risk (RR)(HIP)=1.91, RR(ANY)=1.33, P900 pg/ml were associated with an elevated risk of any new fracture (RR=1.72, P<0.05) versus PTH 150-300. The results suggest that greater selectivity in prescribing several classes of psychoactive drugs and more efficient treatment of secondary hyperparathyroidism may help reduce the burden of fractures in HD patients