Klotho and Fibroblast Growth Factor 23 Are Independent of Vitamin D, and Unlike Vitamin D, Are Not Associated With Graft- and Patient Survival After Kidney Transplantation.

Short-term survival after kidney transplantation is excellent but long-term survival remains suboptimal. The aim of the study was to explore the relationship between soluble α-Klotho (sKlotho) and intact fibroblast growth factor 23 (iFGF23) measured 8 wk and 1 y posttransplant with long-term graft- and patient survival in a cohort of kidney transplant recipients with deficient and nondeficient vitamin D (25[OH]D) levels. Methods: Vitamin D, sKlotho, and iFGF23 were measured 8 wk and 1 y posttransplant in 132 recipients transplanted between November 2012 and October 2013. Results: Of the 132 kidney transplant recipients, 49 had deficient vitamin D levels (<30 nmol/L) and 83 had nondeficient vitamin D levels (≥30 nmol/L) at 8 wk posttransplant. The mean age was 51 y and the median follow-up was 7.4 y. At 1 y posttransplant, vitamin D increased significantly. There were no significant differences in sKlotho or iFGF23 levels between the 2 vitamin D groups neither at 8 wk nor 1 y. sKlotho increased significantly and iFGF23 decreased significantly in the whole cohort. During the follow-up, there were 36 graft losses (27%) and 27 deaths (20%). Ninety-four percent of the transplant recipients with nondeficient vitamin D levels were alive with a well-functioning graft after 5 y using Kaplan-Meier survival estimates, compared with 84% of the patients with deficient vitamin D levels (P = 0.014). Klotho and FGF23 levels did not influence graft- and patient survival. Conclusions: In this nationwide cohort of kidney transplant recipients, long-term graft- and patient survival were significantly better in patients with vitamin D ≥30 nmol/L 8 wk posttransplant compared with those with vitamin D <30 nmol/L. sKlotho levels increased and iFGF23 levels decreased from 8 wk to 1 y posttransplant. Klotho and FGF23 levels were not associated with graft- and patient survival.

Glycated albumin and continuous glucose monitoring metrics across pregnancy in women with pre-gestational diabetes.

INTRODUCTION: Glycated albumin (GA), a biomarker reflecting short-term glycaemia, may be useful to assess glycaemic control in pregnancy. We examined the association between GA and continuous glucose monitoring (CGM) metrics across gestation. METHODS: In this prospective cohort study including 40 women with pre-gestational diabetes, blood samples for analysis of GA and glycated haemoglobin A1c (HbA1c) were collected at pregnancy week 12, 20, 24, 28, 32 and 36. In the CGM-group (n = 19), CGM data were collected from first trimester until pregnancy week 36. Receiver operating characteristic (ROC) curves were used to assess the accuracy of GA and HbA1c to detect poor glycaemic control, using CGM metrics as the reference standard. This study was conducted at Stavanger University Hospital, Norway, in 2016-2018. RESULTS: Glycaemic control improved across gestation with more time spent in target range, coinciding with decreased glycaemic variability and lower mean GA level. There was statistically significant correlation between GA and most CGM metrics. The area under the ROC curves (AUC) for detecting time in range <70% and time above range >25% for the pregnancy glucose target 63-140 mg/dl (3.5-7.8 mmol/L) were 0.78 and 0.82 for GA, whereas AUCs of 0.60 and 0.72 were found for HbA1c, respectively. CONCLUSIONS: Higher GA levels were associated with less time spent in target range, more time spent in the above range area and increased glycaemic variability. GA was more accurate than HbA1c to detect time above range >25% and time in range <70%.

Glycated albumin in pregnancy: LC-MS/MS-based reference interval in healthy, nulliparous Scandinavian women and its diagnostic accuracy in gestational diabetes mellitus.

Glycated albumin (GA) may be a useful biomarker of glycemia in pregnancy. The aim of this study was to establish the reference interval (RI) for GA, analyzed by liquid chromatography-tandem mass spectrometry (LC-MS/MS), in healthy, nulliparous pregnant women. In addition, we assessed the accuracy of GA and glycated hemoglobin A1c (HbA1c) in the diagnosis of gestational diabetes mellitus (GDM). Finally, we explored the prevalence of GDM in healthy nulliparas, comparing three diagnostic guidelines (WHO-1999, WHO-2013 and the Norwegian guideline). The study was carried out at Stavanger University Hospital, Norway, and included a study population of 147 pregnant nulliparous women. An oral glucose tolerance test (OGTT) was performed and used as the gold standard for GDM diagnosis. Blood samples for analysis of GA and HbA1c were collected at pregnancy week 24-28. A nonparametric approach was chosen for RI calculation, and receiver operating characteristic (ROC) curves were used to evaluate the diagnostic performance of GA and HbA1c. The established RI for GA in 121 pregnant women was 7.1-11.6%. The area under the ROC curves (AUCs) were 0.531 (GA) and 0.627 (HbA1c). According to the WHO-1999, WHO-2013 and the Norwegian guideline, respectively, 24 (16%), 36 (24%) and 21 (14%) women were diagnosed with GDM. Only nine women (6%) fulfilled the GDM-criteria of all guidelines. In conclusion, we established the first LC-MS/MS-based RI for GA in pregnant women. At pregnancy weeks 24-28, neither GA nor HbA1c discriminated between those with and without GDM. Different women were diagnosed with GDM using the three guidelines.

Neurofilament light in plasma is a potential biomarker of central nervous system involvement in systemic lupus erythematosus.

BACKGROUND: Neuropsychiatric manifestations (NP) are common in systemic lupus erythematosus (SLE). However, the pathophysiological mechanisms are not completely understood. Neurofilament light protein (NfL) is part of the neuronal cytoskeleton. Increased NfL concentrations, reflecting neurodegeneration, is observed in cerebrospinal fluid (CSF) in several neurodegenerative and neuroinflammatory conditions. We aimed to explore if plasma NfL could serve as a biomarker for central nervous system (CNS) involvement in SLE. METHODS: Sixty-seven patients with SLE underwent neurological examination; 52 underwent lumbar puncture, while 62 underwent cerebral magnetic resonance imaging (MRI). We measured selected auto-antibodies and other laboratory variables postulated to have roles in NP pathophysiology in the blood and/or CSF. We used SPM12 software for MRI voxel-based morphometry. RESULTS: Age-adjusted linear regression analyses revealed increased plasma NfL concentrations with increasing creatinine (ß = 0.01, p < 0.001) and Q-albumin (ß = 0.07, p = 0.008). We observed higher plasma NfL concentrations in patients with a history of seizures (ß = 0.57, p = 0.014), impaired motor function (ß = 0.36, p = 0.008), increasing disease activity (ß = 0.04, p = 0.008), and organ damage (ß = 0.10, p = 0.002). Voxel-based morphometry suggested an association between increasing plasma NfL concentrations and the loss of cerebral white matter in the corpus callosum and hippocampal gray matter. CONCLUSION: Increased plasma NfL concentrations were associated with some abnormal neurological, cognitive, and neuroimaging findings. However, plasma NfL was also influenced by other factors, such as damage accrual, creatinine, and Q-albumin, thereby obscuring the interpretation of how plasma NfL reflects CNS involvement. Taken together, NfL in CSF seems a better marker of neuronal injury than plasma NfL in patients with SLE.

Exploring health literacy in patients with chronic kidney disease: a qualitative study.

BACKGROUND: Patients with chronic kidney disease make day-to-day decisions about how to self-manage their disease. Chronic kidney disease (CKD) includes a risk for progression towards end-stage renal disease and the development of comorbidities, such as cardiovascular disease, which represents the leading cause of death among these patients. To reduce these risks, CKD patients are recommended to follow a healthy lifestyle with physical activity, food and fluid restrictions, and adherence to complex medication regimes throughout all phases of the disease. To manage the complexity of this health situation, health literacy (HL) is considered essential. The current prevailing understanding is that HL is a multidimensional concept and comprises a range of cognitive, affective, social, and personal skills that determine the motivation and ability to gain access to, understand, and use health information. Recently, we investigated multiple aspects of HL in CKD patients in a quantitative cross-sectional study utilizing the Health Literacy Questionnaire (HLQ) and observed that finding good health information and appraising health information were the most challenging aspects of HL. This study aimed to explore CKD patients' lived experiences of different dimensions of HL presented in the HLQ. METHODS: This qualitative study utilized in-depth semistructured interviews. Twelve patients with different levels of HL were included. The interviews were analyzed using thematic analysis as described by Braun and Clarke. RESULTS: We identified three main themes that were significant for CKD patients' HL: 1. Variation in people's attitudes and behavior as health information seekers, 2. The problem of fragmented healthcare in the context of multimorbidity makes the healthcare system challenging to navigate, and 3. The value of a good relationship with healthcare providers. CONCLUSION: CKD patients take different approaches to health information. Limiting or avoiding health information may be a strategy used by some individuals to cope with the disease and does not necessarily mean that health information is inaccessible or difficult to understand. Comorbidity and a fragmented healthcare system can make the healthcare system challenging to navigate. A good and trusting relationship with healthcare providers seems to promote several aspects of HL and should be promoted to optimize CKD patients' HL.

A cross-sectional study of health literacy in patients with chronic kidney disease: Associations with demographic and clinical variables.

AIM: The aim of this study was to investigate health literacy in patients with chronic kidney disease in a multidimensional perspective. DESIGN: A descriptive, cross-sectional study. METHODS: Patients with chronic kidney disease at stages 3-5 were included in the study between February-August 2017 (N = 187). Health literacy was measured by the Health Literacy Questionnaire (HLQ). Multiple linear regression analysis was performed to identify associations between health literacy and demographic and clinical variables. Hierarchical cluster analysis was performed to identify characteristics of groups with high and low health literacy. RESULTS: Finding and critical appraise health information were the most challenging dimensions of health literacy. Female gender, lower level of education, greater number of prescribed medications and depressive symptoms were associated with lower health literacy. The group identified with lowest health literacy was further characterized by living alone and presence of comorbidity.

The impact of calcineurin inhibitors on neutrophil gelatinase-associated lipocalin and fibroblast growth factor 23 in long-term kidney transplant patients.

BACKGROUND: Neutrophil gelatinase-associated lipocalin (NGAL), a protein with bacteriostatic functions rapidly excreted from stimulated or damaged epithelial cells, is elevated in acute and chronic kidney disease. A calcineurin dependent signaling pathway for fibroblast growth factor 23 (FGF23) has been revealed, but the effect of calcineurin inhibitors (CNIs) on the levels of NGAL and markers of mineral metabolism in long-term kidney transplant patients has not been explored. METHODS: In a cross-sectional study, 39 patients who received a first kidney transplant more than 10 years ago were split into two groups based on whether (n=28) or not (n=11) they used CNIs. Only patients with well-functioning grafts defined as an estimated glomerular filtration rate ≥45 mL/min per 1.73 m2 were included. RESULTS: The median levels of NGAL, intact parathyroid hormone (iPTH), and iFGF23 were significantly higher in CNI users vs CNI nonusers, 167.0 (134.0-235.0) ng/mL vs 105.0 (91.3-117.0) ng/mL, P<.001, 13.8 (10.0-17.3) pmol/L vs 8.4 (6.4-9.9) pmol/L, P=.003, and 81.6 (56.4-116.5) pg/mL vs 61.8 (43.3-72.1) pg/mL, P=.04 respectively. CONCLUSIONS: The median levels of iFGF23 were higher in CNI users compared to CNI nonusers giving support to the notion of a CNI induced FGF23 resistance in the parathyroid. The net result of CNIs side effects needs to be further explored.

Neutrophil Gelatinase-Associated Lipocalin, Fibroblast Growth Factor 23, and Soluble Klotho in Long-Term Kidney Donors.

BACKGROUND: The best treatment for end-stage renal disease (ESRD) is kidney transplantation. Twenty-seven percent of transplantations in Norway are from living donors. Recent studies have shown an increased risk of ESRD and increased mortality in donors. The aim of this study was to determine if the levels of the new biomarkers neutrophil gelatinase-associated lipocalin (NGAL), soluble Klotho (sKlotho), and fibroblast growth factor 23 (FGF23) are changed in kidney donors with normal kidney function defined as an estimated glomerular filtration rate (eGFR) >60 ml/min/1.73 m2 compared to patients with chronic kidney disease (CKD) stages 3-5 and healthy controls. METHODS: This is a cross-sectional, observational, single-center study including 35 kidney donors with an eGFR ≥60 ml/min/1.73 m2 5 years after donation, 22 patients with CKD stage 3 (eGFR 30-59 ml/min/1.73 m2), 18 patients with CKD stage 4 (eGFR 15-29 ml/min/1.73 m2), 20 patients with CKD stage 5 (eGFR <15 ml/min/1.73 m2), and 35 controls comparing levels of biomarkers in long-term kidney donors with those in CKD patients and healthy controls. RESULTS: The level of log NGAL was significantly higher in donors than in healthy controls (2.02 ± 0.10 vs. 1.89 ± 0.10 ng/ml; p < 0.001), and the level increased with declining kidney function. The log FGF23 level was nonsignificantly higher in donors than in controls, but it significantly increased with declining kidney function. The log sKlotho levels were significantly lower in patients with CKD stages 4 and 5 than in controls, but no difference was revealed between controls and donors. CONCLUSION: Kidney donors have significantly higher levels of NGAL than healthy controls after a median of 15 years (range 5-38). NGAL could be a valuable diagnostic marker in the future. FGF23 and sKlotho were not significantly different between donors and controls.

Benchmarking by HbA1c in a national diabetes quality register--does measurement bias matter?

BACKGROUND: Bias in HbA1c measurement could give a wrong impression of the standard of care when benchmarking diabetes care. The aim of this study was to evaluate how measurement bias in HbA1c results may influence the benchmarking process performed by a national diabetes register. METHODS: Using data from 2012 from the Norwegian Diabetes Register for Adults, we included HbA1c results from 3584 patients with type 1 diabetes attending 13 hospital clinics, and 1366 patients with type 2 diabetes attending 18 GP offices. Correction factors for HbA1c were obtained by comparing the results of the hospital laboratories'/GP offices' external quality assurance scheme with the target value from a reference method. RESULTS: Compared with the uncorrected yearly median HbA1c values for hospital clinics and GP offices, EQA corrected HbA1c values were within ±0.2% (2 mmol/mol) for all but one hospital clinic whose value was reduced by 0.4% (4 mmol/mol). Three hospital clinics reduced the proportion of patients with poor glycemic control, one by 9% and two by 4%. CONCLUSIONS: For most participants in our study, correcting for measurement bias had little effect on the yearly median HbA1c value or the percentage of patients achieving glycemic goals. However, at three hospital clinics correcting for measurement bias had an important effect on HbA1c benchmarking results especially with regard to percentages of patients achieving glycemic targets. The analytical quality of HbA1c should be taken into account when comparing benchmarking results.