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Advances in dermatology and venereology Acta Dermato-Venereologica
Fibroblast Growth-factor 23 and Calcium-binding Proteins are not Associated with Chronic Itch in Patients on Haemodialysis
Thomas METTANG 1, Kevin KUNZMANN 2, Heinz-Jürgen ROTH 3 and Elke WEISSHAAR 4
1
Department of Nephrology, DKD Helios Clinic, DE-65191 Wiesbaden, 2 Department of Endocrinology, Labor Limbach Heidelberg, 3 Department of Medical Biometry and Informatics, and 4 Department of Clinical Social Medicine, Occupational and Environmental Dermatology, University of Heidelberg, Germany. E-mail: t _ mettang @ t-online. de Accepted Sep 19, 2016; Epub ahead of print Sep 27, 2016
Chronic itch( CI) in haemodialysis, often termed uraemic pruritus, is a frequently experienced, tormenting and challenging symptom and a burden in afflicted patients( 1).
There has been an ongoing discussion about whether CI in chronic kidney disease is brought about by the common disturbance of calcium / phosphate homeostasis. This notion is supported by a number of observations. In the late 1960s, itch was reported to be resolved by parathyreoidectomy in patients with both severe hyperparathyroidism and CI( 2). Later Blachley et al.( 3) reported an increased calcium / phosphate load in the skin of patients with CI in haemodialysis and Momose et al.( 4) were able to demonstrate a disrupted calcium gradient in the skin of patients with CI.
An observational study found that patients with CI had higher serum-calcium levels( 5). It has been proposed recently that a vicious circle of metabolic derangements( malnourishment, inflammation, arteriosclerosis) may explain the exaggerated morbidity and mortality in a subset of haemodialysis patients. Inflammation might be the most deleterious factor in this scenario, contributing, among other factors, to the occurrence of CI in haemodialysis( 6, 7). It has also been shown that Fetuin-A, an important calcium-binding circulating protein, is downregulated by progressive inflammation in haemodialysis patients, thus promoting tissue-calcification( 8). Similarly, matrix Gla protein( MGP) has been shown experimentally to inhibit vascular calcifications( 9), whereas high levels of fibroblast growth-factor 23( FGF23), a potent player in calcium / phosphate-regulation, seem to be associated with increased inflammation and morbidity and mortality in patients with chronic kidney disease( CDK)( 10).
In a previous study we measured Fetuin-A levels in a small number of patients on haemodialysis and did not find any significant differences between patients with and without CI( 11). In the present study a larger number of patients was investigated for CI and a potential decrease in serum levels of calcium-binding proteins, such as Fetuin-A and MGP, or other factors known to influence calcium-phosphate regulation( e. g. FGF23) potentially leading to an increased tissue deposition of calcium salts.
PATIENTS AND METHODS
In a hospital-based single centre patients were screened for chronic itch( duration > 6 weeks). Eighteen patients reported CI, while another 18 randomly selected patients on haemodialysis did not report having had CI during at least 6 months prior to the investigation. None of the patients had been treated with ultraviolet( UV) phototherapy in the 6 months prior to this study. After having obtained informed consent, patients with CI were asked to score the intensity of current itch using a visual analogue scale( VAS) ranging from 0( no itch) to 10( worst imaginable itch). In both groups 10 ml blood was taken immediately after puncture of the arterio-venous fistula for haemodialysis.
The following laboratory measurements were performed: Fetuin-A, 25-hydroxyvitamin D3( 25 [ OH ] D3) total protein, albumin, calcium( corrected for serum albumin), phosphate, and high-sensitivity C-reactive protein( hsCRP). Fetuin-A( ELISA; Epitope Diagnostics, San Diego, CA, USA), MGP( ELISA BI 2062 Biomedica, Vienna, Austria) and FGF 23( C-terminal, ELISA, Biomedica Austria) were determined by means of an enzymelinked immunosorbent assay( ELISA). An electrochemiluminescence immunoassay( ECLIA) was used for measurement of 25( OH) D3. Total protein, calcium and phosphate were measured by means of the automated clinical chemistry analyser( MODU- LAR ANALYTICS ® P-Module( Roche Diagnostics, Penzberg, Germany). Albumin and hsCRP were determined by immunonephelometric measurement( BNII System Siemens Healthcare Diagnostics, Eschborn, Germany).
Statistical analyses were carried out using R 3.1.3 ®. Descriptive statistics were used to report medians and 1 st and 3 rd quartiles for demographic data and the variables under study stratified by itch status. The distribution of sex and the use of cinacalcet and 1-hydroxyvitamin D( 1 [ OH ] D) were provided as absolute and relative frequencies. Continuous variables were tested for differences between the patients reporting CI and non-CI patients, using the non-parametric Mann-Whitney U test or, for nominal variables, the χ 2-test. p-values below 0.05 were considered statistically significant. Due to the explorative nature of the analysis no adjustment for multiple testing was applied.
RESULTS
The median itch intensity of patients with CI was 6.5( Table SI 1). Serum levels of hsCRP of Fetuin A and MGP were significantly higher in patients with CI, but no significant differences were found between the 2 groups in serum-calcium, serum-phosphate, 25 [ OHD3 and FGF23.( Fig. S1 1, Table SI 1). Time on dialysis and hsCRP were
1 https:// www. medicaljournals. se / acta / content / abstract / 10.2340 / 00015555-2536
This is an open access article under the CC BY-NC license. www. medicaljournals. se / acta Journal Compilation © 2017 Acta Dermato-Venereologica. doi: 10.2340 / 00015555-2536 Acta Derm Venereol 2017; 97: 381 – 382