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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