Aneta Czupryniak, Anna Kałużyńska, Anna Półtorak-Krawczyk, Bartosz Ostrowski, Bogusław Więcek, Marcin Tkaczyk Discussion Impaired endothelial function has been postulated as a link between accelerated atherosclerosis and NS [16, 17]. Children with NS are known to present with vascular com- plications much more often than the general population. Interestingly, there have been no studies assessing the peripheral circulation in NS; however, it was found that sympathetic hyperreactivity often accompanies proteinuric renal diseases [18]. The defective baroreflex control over renal sympathetic nerves might also be related to impaired renal sodium handling [18, 19]. Amongst the wide range of drugs prescribed in NS only CsA has been reported to directly influence endothelium and sympathetic activity and raise blood pressure by these pathways [5, 12]. In our study, the rate of temperature change in fingers after CST was significantly lower in NS patients treated with CsA than in healthy children, which suggests that the peripheral circulation is impaired in this group of subjects. The microcirculation damage in the study group was not severe enough to increase prevalence of RP, a symptom of significant vascular regulation impairment [20, 21]. This may result from either the young age of the patients or relatively low doses of CsA used due to its toxicity. Sharma et al. reported a case of a post-renal transplant patient in whom RP always occurred at the time of CsA dose increase and when plasma CsA concentration exceeded 300 ng/ml. Dose reduction and plasma CsA below 200 ng/ml led to RP resolution [10]. Static measurements of temperature distribution cannot serve as an objective examination as they considerably depend on the temperature of the surroundings. That was the reason why we applied a dynamic method of constant temperature registration after cooling the hands that detects even small but significant disturbances of blood flow. Apart from the destructive effect of NS on vasculature, CsA treatment may additionally distort vascular regulation. Lucini et al. and Stein et al. reported similar findings in patients treated with CsA after heart transplantation and with rheumatoid arthritis [5, 22]. Stein et al. found that CsA directly impaired vascular vasodilation through endothelium-related pathways rather than affecting nervous regulation [22]. Both sympathetic and parasympathetic parts of the autonomic nervous system are involved in vascular regulation. Ewing’s battery has long been used as a reliable tool for autonomic nervous function assessment. Heart rate variability with deep breathing, heart rate response to Valsalva manoeuvre and heart rate response to standing (30 : 15 ratio) verify mostly parasympathetic function, and blood pressure response to standing assesses sympathetic adrenergic function [11]. However, no relation between autonomic nervous system activity and microcirculation impairment in NS children was found. Both NS and CsA treatment may exert an effect on peripheral nerves, but in NS patients only the intrarenal sympathetic nervous system function was disturbed and was closely related to the renal sodium handling [8, 18, 23]. A distinct influence of CsA on renal and extrarenal small vessel reactivity was observed in transplanted rats by Gabriëls et al. [24]. Previous studies have reported on CsA-related neurotoxicity within the autonomic nervous system, while in contrast a recent publication questioned the role of increased sympathetic activity in the CsA-induced blood pressure rise [13, 22]. It seems that the doses of CsA routinely used in children and adolescents are probably too low to have a significant detrimental effect on autonomic nervous system activity [12]. Cyclosporine A nephrotoxicity depends on its vasoconstricting effect on afferent glomerular arterioles [7]. It was found that CsA decreased mRNA synthesis of nitric oxide synthase in rodents and induced direct endothelial damage [25]. These mechanisms might be responsible for CsA-induced hypertension. In our study group we had 5 children (26%) with hypertension, when in other studies the percentage of hypertensive children among CsA-treated patients varied from 10% to 12% [1]. Perhaps this increase may be related to longer CsA treatment (44 m vs. 34 or 22 in other studies) [1]. Many non-invasive techniques have been developed to measure arterial and peripheral blood flow in humans. The thermographic methods applied in our study were less invasive than ultrasound brachial artery relaxation in response to transient ischaemia applied in adult patients [26]. Thermography has become a standard indirect measurement in diagnosis of RP as painless and easily analysed [14]. It was observed that the changes in superficial hand temperature correlated positively with small vessel reactivity and furthermore might be applied to assess endothelial dysfunction [27]. Our study, however, has some limitations. The number of studied patients was relatively small, and drawing unequivocal conclusions from our experiment would be premature. Moreover, we have not studied children with NS but not treated with CsA, which if we had would have enabled us to precisely discern between the vascular damaging impact of NS and CsA treatment. However, one reason for that was the fact that at our centre nowadays few children with steroid-dependent (similar by clinical classification) NS are not treated with CsA. We tried to reduce this bias by qualifying 576 Arch Med Sci 4, August / 2010