Nikolay Mukhin

End-stage renal disease in ANCA-associated vasculitis

Abstract The outcomes in patients with anti‐neutrophil cytoplasmic antibody (ANCA)‐associated vasculitis have improved significantly over the past decades, although a significant proportion of them still reach end‐stage renal disease (ESRD). Renal replacement therapy (RRT) is associated with a relatively low risk of relapsing vasculitis as a result of anti‐rejection treatment after kidney transplantation or quiescence of the autoimmune process in haemodialysis patients, but a flare of vasculitis in the latter setting presents a challenge because the treatment is poorly tolerated. There are benefits of rituximab in haemodialysed patients, as it is more steroid sparing in the treatment of extrarenal disease. More favourable outcomes of kidney transplantation compared with haemodialysis support its use as a preferable method of RRT in patients with vasculitis remission or low disease activity.

[Impact of anemia correction on the production of the circulating morphogenetic protein α-Klotho in patients with Stages 3B-4 chronic kidney disease: A new direction of cardionephroprotection].

AIM To investigate the impact of anemia correction with erythropoiesis stimulants on the serum level of the circulating morphogenetic protein α-Klotho in patients with Stages 3B--4 chronic kidney disease (CKD). SUBJECTS AND METHODS 64 patients aged 42±8 years with Stages 3B--4 nondiabetic CKD were examined and divided into 2 groups: 1) 32 patients with anemia (the target hemoglobin levels could be achieved and kept with erythropoietin and iron saccharate in 20 patients (Group A) and those could not be done in 12 patients (Group 1B). A control group (Group 2) consisted of 32 non-anemic patients matched for gender, age, and degree of a glomerular filtration rate (GFR) reduction. Along with iron exchange indicators, the time course of changes in serum Klotho levels were examined in all the 64 patients during screening and one year after the end of the study. For correction of anemia, 32 patients with this condition (Groups 1A and 1B) took short-acting epoetin (hypodermic recormon 2,000 IU thrice per week + iron (intravenous venofer 5 ml of 100 mg once per week)) under control of hemoglobin levels and serum transferrin iron and ferritin saturation. After achieving the target hemoglobin level of 110-120 g/l, for its keeping, all the patients received, instead of short-acting epoetin, long-acting hypodermic darbepoetin-α 1.5 µg once every 2 months and intravenous iron saccharate 100 mg once every 2 weeks. RESULTS Among the 32 anemic patients in Group 1, 20 (63%) (Group 1 A) could achieve the target hemoglobin level (110--120 g/l) and maintain it within this range, by performing therapy with epoitin-β + iron saccharate; anemia (the hemoglobin level of <110 g/l) persisted in 12 (37%) patients (Group 1B) despite the fact that epoetin and iron saccharate had been administered. Group 1A was noted to have an increase in α-Klotho concentrations by an average of 100±11.6-pg/ml as compared to Group 1B (by only 72±4.2 pg/ml). At the same time, the α-Klotho levels in the control group by the end of the follow-up decreased by an average of 210±12.9 pg/ml as compared to the prescreening value. There was a direct correlation between hemoglobin and serum ferritin concentrations and iron ferritin saturation percentage and α-Klotho levels. It was ascertained that the hemoglobin concentration of ≥110 g/l with a sensitivity of 89% and a specificity of 75% could predict higher serum α-Klotho levels in CKD. The same patients were found to have an inverse relationship between the serum level of α-Klotho and the risk of cardiovascular events. CONCLUSION The serum level of the protein Klotho is not only a marker for the severity of CKD and its complications (anemia, left ventricular hypertrophy, and heart failure), but also a pathogenetic factor of CKD progression. Anemia correction with erythropoiesis stimulants has been shown to enhance the renal and extrarenal production of α-Klotho.

HCV-associated cryoglobulinemia vasculitis: are its days numbered?

We read with great interest the article by Saadoun et al 1 who investigated the efficacy and safety of a 24-week treatment with sofosbuvir and ribavirin in a small, open-label and uncontrolled study of patients with hepatitis C virus (HCV)-associated cryoglobulinemia vasculitis. However, the limitations of the VASCUVALDIC study diminish the validity of the conclusions, although we agree with the authors that it would be unethical to delay effective antiviral therapy given the established role of HCV in the development of cryoglobulinemia vasculitis and its unfavourable prognosis. As expected, the rate of sustained virological response (SVR) was higher (74%) than in previous trials of interferon-based antiviral treatment in patients with HCV-associated cryoglobulinemia vasculitis.2 ,3 However, this looks relatively moderate in light of the current efficacy of the interferon-free, all-oral antiviral regimens (up to 95%–100%). Nonetheless, the SVR rate was comparable with that identified in the previous phase III sofosbuvir plus ribavirin trial in patients with HCV infection.4 We can also assume that the proportion of virological responders among patients with HCV-associated cryoglobulinemia …

Giant cell arteritis: Genetic and epigenetic aspects

The paper describes clinical cases in 2 patients (brothers) with giant cell arteritis. It analyzes the genetic and epigenetic aspects of the disease. The data available in the Russian and foreign literature are given.

Autoinflammatory diseases and kidney involvement

Autoinflammatory disease (AID) is a new concept formulated from the results of studying the pathogenesis of familial periodic fevers, a heterogeneous group of genetically determined diseases characterized by causelessly recurrent exacerbations of the inflammatory process due to genetically determined disorders of innate immunity and accompanied by uncontrolled hypersecretion of interleukin-1 (IL-1). These mechanisms were a basic model for understanding a wide range of rheumatologic and other inflammatory diseases of the internal organs. The late diagnosis of AIDs and their ineffective treatment increase the risk for the development and progression of secondary AA amyloidosis. Elaboration of both clinical and effective laboratory criteria for diagnosing autoinflammation is of great importance for determining the tactics of anti-inflammatory therapy and prevention of complications.

[The serum level of the morphogenetic protein fibroblast growth factor 23 (FGF-23) as a marker for the efficiency of hyperphosphatemia therapy with phosphate-binding agents in chronic kidney disease].

AIM To study whether the excessive production of serum fibroblast growth factor 23 (FGF-23) may be reduced with phosphate-binding agents to treat hyperphosphatemia in patients with Stage VD chronic kidney disease (CKD). MATERIALS AND METHODS The investigation enrolled 25 patients with Stage VD CKD on regular hemodialysis (HD) (12 patients with chronic glomerulonephritis, 8 with tubulointerstitial nephritis, and 5 with hypertensive nephrosclerosis); among them there were 15 men and 10 women at the age of 21 to 65 years; their mean age at inclusion in the study was 43±4.5 years. The clinical, laboratory, and instrumental examination similar to that in patients with the early stages of CKD was done. Serum FGF-23 levels (Human FGF-23 ELISA kit using monoclonal antibodies to the full FGF-23 molecule) were investigated in all the 25 patients. A whole blood sample was taken 2 days after the last session of HD before initiation of its regular procedure. RESULTS The elevated serum FGF-23 concentrations in the patients on regular HD correlated with their HD duration (r=0.508; p<0.001). Along with this, a strong direct correlation (r=0.522; p<0.001) was found between the concentration of FGF-23 in the serum and inorganic phosphorus; at the same time hyperphosphatemia was less significantly associated with higher serum intact parathyroid hormone (PTH) levels (r=0.398; p<0.05). Lower FGF-23 and PHT levels were noted in a group of patients who could achieve and maintain the target serum inorganic phosphorus level (0.9-1.45 mmol/l) compared to that of patients with uncorrected hyperphosphatemia (>1.45 mmol/l) (p<0.01). A decrease in FGF-23 and PHT levels was achieved chiefly in the patients who had used phosphate-binders that contained no calcium (sevelamer hydrochloride). CONCLUSION Lower FGF-23 levels were observed in the patients with CHD on regular HD who can achieve and maintain the target serum inorganic phosphorus level when using phosphate-binders that do not contain calcium than in those with uncorrected hyperphosphatemia (p<0.01).

FRI0455 Serum Surfactant Protein D in Systemic Sclerosis Lung Fibrosis by Presence or Absence of Gastroesophageal Reflux: A Crossectional Monocentric Study

Background Serum surfact protein D (SP-D) levels are elevated in systemic sclerosis interstitial lung disease (SSc-ILD) (1). Gastroesophageal reflux disease (GERD) is suggested to be a risk factor for SSc-ILD (2). However, previous studies did not analyze SP-D by subgroups of SSc-ILD patients with and without GERD. Objectives Aim of our study was to evaluate SP-D as a biomarker of severity of SSc-ILD in the presence or absence of GERD. Methods 56 SSc patients underwent chest computertomography and lung function test to evaluate ILD, and gastroesophagoscopy for confirmation/exclusion of GERD. Extend of lung fibrosis >20%, presence of ground-glass opacity (GGO) and honey combing (HC) were compared between SSc-ILD patients with and without GERD by chi-square test. Serum samples were analyzed for SP-D by Enzyme Linked Immunosorbent Assay. Correlations were evaluated by Spearman rank correlation test. Kruskal-Wallis test or Mann–Whitney U test were used to compare SP-D levels between different patient groups (values in ng/ml, mean±SD). Results 49 patients (87.5%) were female, mean age was 46.5±14.4 years. 43 patients had limited and 13 patients diffuse cutaneous involvement. 27 patients had coexistent ILD and GERD (group 1), 16 patients had ILD but no GERD (group 2) and 13 patients had no ILD or GERD (group 3). All patients with GERD by gastroesophagoscopy had signs of ILD by computer tomography. SSc-ILD patients with vs without GERD had statistically significant more often an extend of lung fibrosis >20% (20/37 (74.1%) vs 6/16 (37.5%, p=0.018) and tendentially more often GGO (19/27 (70.4%) vs 7/16 (43.75%), p=0.084), but there was no difference in presence of HC. The levels of SP-D were not significant different between male and female (286±97 vs 227±170, p=0.169) neither between diffuse and limited cutaneous SSc patients (291±198 vs 218±150, p=0.218). In addition, SP-D did not correlate with age (r=0.221, p=0.102) or disease duration (r=-0.164, p=0.226). SP-D levels were higher in group 1 compared to group 2 and group 3 (316±156 ng/ml vs 237±134 ng/ml va 62±19 ng/ml, p<0.001), which is shown in figure 1. SP-D levels were highly correlated with the extend of lung fibrosis (r=0.783, p<0.001), and patients with FVC <70% had higher levels compared to patients without restrictive lung function (387±175 vs 189±130, p=0.001). Moreover, the level of SP-D was higher in SSc-ILD patients with than without GGO (334±146 vs 214±133, p=0.005) and higher in patients with than without HC (367±160 vs 223±111, p=0.002). Conclusions ILD-SSc patients with GERD have a more severe lung involvement and higher SP-D levels then ILD-SSc patients without GERD. Moreover, SP-D levels are much lower in SSc patients without ILD or GERD. Thus, our results suggest that GERD is linked with extend of lung fibrosis and may contribute to GGO, as SP-D was a valuable biomarker to monitor the severity of SSc-ILD. References Kumánovics et al.: Comprehensive investigation of novel serum markers of pulmonary fibrosis associated with systemic sclerosis and dermato/polymyositis. Clin Exp Rheumatol. 2008. Christmann et al.: Gastroesophageal reflux incites interstitial lung disease in systemic sclerosis: clinical, radiologic, histopathologic, and treatment evidence. Semin Arthritis Rheum. 2010. Disclosure of Interest None declared