Translated to Russian by Elena Kamyshova, edited by Elena Zakharova Translation initiated by Russian Doalysis Society» Goce Spasovski Consultant Nephrologist, State University Hospital Skopje, Skopje, Macedonia. Raymond Vanholder Consultant Nephrologist, Ghent University Hospital, Ghent, Belgium. Состав Рабочей группы Bruno Allolio Consultant Endocrinologist, Wurzburg University Hospital, Wurzburg, Germany. Djillali Annane Consultant Intensivist, Raymond Poincare Hospital, University of Versailles Saint Quentin, Paris, France. Steve Ball Consultant Endocrinologist, Newcastle Hospitals and Newcastle University, Newcastle, UK. Daniel Bichet Consultant Nephrologist, Hospital, Montreal, Canada. Guy Decaux Consultant Internal Medicine, Erasmus University Hospital, Brussels, Belgium. Wiebke Fenske Consultant Endocrinologist, Wurzburg University Hospital, Wurzburg, Germany. Ewout Hoorn Consultant Nephrologist, Erasmus Medical Centre, Rotterdam, The Netherlands. Carole Ichai Consultant Intensivist, Nice University Hospital, Nice, France. Michael Joannidis Consultant Intensivist, Innsbruck University Hospital, Innsbruck, Austria. Alain Soupart Consultant Internal Medicine, Erasmus University Hospital, Brussels, Belgium. Robert Zietse Consultant Nephrologist, Erasmus Medical Centre, Rotterdam, The Netherlands. Группа по сбору и анализу доказательств Maria Haller Specialist Registrar Nephrology, KH Elisabethinen Linz, Linz, Austria. Evi Nagler Specialist Registrar Nephrology, Ghent University Hospital, Ghent, Belgium. Wim Van Biesen Consultant Nephrologist, Chair of ERBP, Ghent University Hospital, Ghent, Belgium. Sabine van der Veer Implementation Specialist, Amsterdam Medical Centre, Amsterdam, The Netherlands

The kidney plays a leading role in the creation and maintenance of physiological conditions in pregnancy for both mother and fetus. These conditions can be critical for the mother, because they include an increase in circulating blood volume, which can lead to a rise in blood pressure (hyperdynamic circulation type) that represents a danger for the fetus. Maintaining normal blood pressure in the hyperdynamic circulation type also largely driven by the kidney. The leading role in the changes in hormonal levels during pregnancy belongs to the pituitary gland. It regulates the adrenal glands, increasing the production of adrenotropic hormone, glucocorticoids and mineralocorticoids. The pituitary gland is involved in regulation of the immune system of the mother, which is critical in implantation of fertilized cells in the myometrium. The relationship of systemic and placental angiotensin II is discussed. An important role of progesterone (pregnancy hormone) under both normal and pathological pregnancy is described. It is the depletion of the adaptive functions of the kidney that is the reason for the switch stage 1 pre-eclampsia in second with renal symptoms (proteinuria, edema, and hypertension). Prevention and treatment of pre-eclampsia should be included in the maintenance and restoration of hyperdynamic circulation type. In modern literature the role of cardiotonic steroids in the mechanism of occurrence of preeclampsia is widely discussed. Available experimental and clinical data suggest that using antibodies to cardiotonic steroids is very promising for the treatment of preeclampsia.

Treatment of acute kidney injury (AKI) using renal replacement therapy is still associated with an unacceptably high mortality rate, with high frequency of transformation to chronic kidney disease and the need for dialysis therapy. All these reason stimulate a search for an alternative approach in the treatment of these patients. Aquaporins discovered in 2003 by P. Agre and R. MacKinnon are important integral transport proteins that contribute to maintaining the water homeostasis. In the case of acute kidney injury, impaired function of various types of aquaporins is a key pathophysiological factor that influences the outcome. Recent studies have established certain features of aquaporin dysfunction in AKI of ischemia/reperfusion or septic origin. In addition, a number of medications which can change the functional activity of aquaporins have been identified. This justifies the use of drugs stimulating expression of aquaporins in patients with AKI associated with polyuria, and inhibiting them when oligoanuria occurs. This review describes the features of aquaporin dysfunction in AKI and possible therapeutic approaches to modulate them in patients with this pathology.

For last ten years a substantial number of facts have been accumulated to reveal a crucial role of mitochondria in the development of acute kidney injury (AKI) under exposure to various damaging factors including ischemia/reperfusion, myoglobinuria, endotoxemic shock and nephrotoxic drugs. All these factors are associated with a distortion of normal functioning of renal mitochondria resulting in impropriate production of reactive oxygen species (ROS). Resultant oxidative stress disrupts or modifies a number of intracellular processes, leading to the loss in the efficiency of tubular epithelium and changes of the vessels reactivity. As a result, severe mitochondrial dysfunction leads to a decrease in the number of active nephrons. The review describes new approaches to the treatment of AKI via targeting the mitochondria. The first approach suggests the usage of new antioxidants selectively accumulated in mitochondria. Resultant high concentrations of antioxidants in these organelles allows one to cease the destructive chain of events underlying AKI and, consequently, to preserve kidney function. The second strategy is a mild uncoupling of mitochondrial respiration and oxidative phosphorylation in order to reduce generation of ROS by the respiratory chain. The third approach is associated with the activation of endogenous mechanisms of tolerance to oxidative stress by «training» the organ through exposure to short periods of ischemia. Pulses of ROS produced by mitochondria in these periods activate signaling pathways that make the organelle more tolerant to ROS-mediated damage. A number of available pharmacological agents are able to activate these pathways and reduce the severity of AKI tested in animal studies.

Last decades Сyclosporin A (CsA) is widely used for treatment of nephrotic syndrome (NS) in patients with several types of glomerulonephritis, mainly those with predominantly podocyte damage. Currently CsA became a useful treatment option for minimal change disease (MCD) and focal segmental glomerulosclerosis (FSGS), often applied in combination with steroids. CsA is recommended also for steroid-resistant NS or in cases when steroids are contraindicated or not well tolerated. Furthermore, CsA is used to maintain steroid-induced NS remission in steroid-sensitive NS in order to prevent relapses, and also for treatment of relapses. Here we present a review tackling the issues of GN pathogenesis and classification, and CsA influence on T-lymphocytes (immunosuppressive effect), non-immune cells and directly on podocytes (antiproteinuric effect), as actually CsA efficacy in FSGS is referred mostly to inhibition of calcineurin-dependent dephosphorylating and stabilization of podocytes cytoskeleton components, including sinaptopodyn, damaged by permeability factor. We also present available data concerning usage of CsA for treatment of MCD and FSGS.

Aim: to compare the results of the delivered dialysis dose assessment by classical biochemical method and by on-line spectrophotometry of spent dialysate, to analyze the factors able to influence on-line method accuracy. Method: During a yearlong study in a single dialysis center in 143 patients the 1001 parallel Kt/V assessments by spectrophotometry with Ademia option (Dialog Plus, BBraun) - UV-Kt/V and by Daugirdas-II formula with calculation of Kt/V as reference. Results: In the whole group the mean UV-Kt/V was 1.49±0.21 and eKt/V was 1.40±0.19 (p<0.001). The correlation between two methods was high - r=0.868 (p<0.001). Systematic error of spectrophotometric method was +5.7% (+0.083 unit of Kt/V), a random error - 7.3% (±0.106). The linear function (eKt/V)=0.819×(UV-Kt/V)+0,194, R2=0.754 gave the best fit for describing relation between the results. The deviation was not related to Kt/V value, ultrafiltration volume, baseline urea level, urea reduction ratio as well as to age, gender, duration of renal replacement therapy and diagnosis. The discrepancy was slightly higher (in favor UV-Kt/V) at low and high extracorporeal blood flow compared to its mean value (311 ml/min). At 87 of 12 381 dialysis sessions (0.7%) we registered deformed graph of on-line Kt/V related to impairment of blood intake to extracorporeal (13% of such cases), hypotension (11%), access recirculation (3%). Conclusion: Determination of Kt/V on-line by spectrophotometry of spent dialysate is in good consistence with classic blood-side method. It enables the monitoring of delivered dialysis dose at each session and helps searching the reason for discrepancy. The outlook for increasing method accuracy is related with the improvement of the algorithms of spectrophotometry data processing.

The pregnancy has more likely a poorer outcome in patients with chronic kidney disease (CKD) than in general population due to the increased frequency of serious complications including preeclampsia (PE) and placental insufficiency. Objectives: The study was undertaken to assess the effectiveness of heparin and antiplatelet therapy for prevention of complications and improvement pregnancy outcomes in women with chronic renal failure (CRF). Design and methods: the study included 15 women with CKD who already has got a wanted pregnancy during which they have not been treated with heparin and/or antiplatelet agents. At the beginning of a new pregnancy all patients had already CKD stage 3 (median GFR 49 mL/min) and were treated since the early stages of pregnancy with heparin and dipyridamole for the prevention of PE and placental insufficiency. The study group consisted of 16 pregnancies with the use of heparin and antiplatelet agents; the control group was 21 anamnestic pregnancies of the same women without receiving anticoagulants or antiplatelet agents. Results: in the study group the frequency of favorable outcomes of pregnancies was significantly higher than in the control group: 15 out of 16 (93.7%) versus 9 out of 21 (42.9%), p=0.002. None of the patients needed a permanent renal replacement therapy during 12 months after delivery. Conclusions: in women with CKD stage 3 heparin and dipyridamole helped to improve pregnancy outcomes: live birth and survival in the postnatal period without significant deterioration in renal function in mothers during the year.

Objective: The aim of the study was the evaluation of homocysteine transportation by plasma proteins and metabolic abnormalities associated with mitochondrial dysfunction in patients treated with chronic hemodialysis. Materials and Methods: Plasma samples from healthy donors and patients treated with chronic hemodialysis using two types of dialysis solution were studied: commonly used bicarbonate or one with succinate. Homocysteine and glutathione were quantified with HPLC. For evaluation of the filterability protein-bond aminothiols by ultrafiltration procedure we introduce filtering factor (F) that is the ratio of the aminothiol concentration in the ultrafiltrate to its overall concentration in the plasma. Results: In the group of healthy donors the value of 25th percentile of factor F for homocysteine was 0.44. Patients with moderate hyperhomocysteinemia showed the decreased filterability of homocysteine, but not glutathione. Low homocysteine filterability (F<0.44) shows the predominant binding of homocysteine to high molecular weight proteins or to protein aggregates, but not to the albumin fraction. Perhaps, the high value of F characterizes the “less dangerous” hyperhomocysteinemia. Conclusion: In this paper, we demonstrated the evaluation of decreased homocysteine transportation by plasma albumin in patients treated with chronic hemodialysis, and introduced the ultrafiltration procedure to estimate the homocysteine binding to macromolecular fraction of blood proteins. Application of succinate-containing dialysis solution was associated with the improvement in the homocysteine filterability of and with decreased level of the mitochondrial dysfunction markers compared to patients receiving bicarbonate hemodialysis.

The aim of the study: was to investigate whether cystatin C is associated with cardiac remodeling in patients with chronic kidney disease (CKD). Methods: The study included 86 patients with non-diabetic CKD. They were divided into 3 groups according to glomerular filtration rate (GFR): group one (n=33) with GFR 89-45 ml/min, group 2 (n=33) - 44-15 ml/min and hemodialysis patients (n=20) were included in the third group. All patients underwent echrocardiography and cystatin C level measurement. Results: The serum Cystatin C level in groups 1, 2, 3 were 1489.49±520.76 ng/ml; 2533.13±621.66 ng/ml; 5166.02±1586.61 ng/ml, respectively. The level of serum Cystatin C positively correlated with arterial hypertension (ρ=0.5, р<0.001) and negatively correlated with GFR (ρ=-0.9; р<0.0001). LVH was detected in 52% patients with CKD. The serum Cystatin C level correlated with left ventricular mass index (ρ=0.51, р<0.0001) and left ventricular hypertrophy (LVH) (ρ=0.5, р<0.0001). Left ventricular diastolic dysfunction (E/A<1.0) was detected in 46% patients with CKD. The Cystatin C level correlated with diastolic dysfunction (ρ=0.3, р=0.01), it was higher in patients with diastolic dysfunction than in patients without it (3013.14±337.6 ng/ml vs 2088.12±199.67 ng/ml; р=0.01, respectively). Multiple regression analysis have showed that factors associated with the cystatin C level were left ventricular mass index (β=0.31, р=0.03) and systolic blood pressure (β=0.25, р=0.036). Conclusion: In stage 3-5 CKD the high level of cystatin C were associated with left ventricular hypertrophy and diastolic dysfunction. The left ventricular mass index and systolic blood pressure correlated independently with the serum cystatin C level.

Cardio-renal cross talks are currently one of the key issues for nephrology, and cardio-renal syndrome is not only widely discussed in literature, but also well defined in clinical setting. Today we would like to draw your attention to case report of a rare syndrome, not only ever been discussed before in the Journal “Nephrology and Dialysis”, but in fact extremely rare observed in patients with ESRD. Authors provide interesting literature data concerning pathogenesis, clinical presentation and work-up findings in the specific type of cardiac damage - Takotsubo cardiomyopathy, firstly described in 1990, and present a case of Takotsubo cardiomyopathy developed during hemodialysis session. Of note, the authors concern hemodialysis procedure itself as a stress trigger for Takotsubo cardiomyopathy. We feel that such straightforward explanation may be somehow confusing. Lack of the information about the details of the hemodialysis session preceding heart attack, and also about the tolerance of hemodialysis treatment and syndialysis complications in the patient treated with hemodialysis for more that a year pose a natural question - why that particular HD session was so stressful for the patient and lead to such serious, life-threatening and unusual complication? We hope that presented case will raise an interest of the audience and update the knowledge of practitioners about the spectrum of cardiac damage in patients with CKD, including dialysis population.

Tako-Tsubo Cardiomyopathy (TCM), also known as stress-induced cardiomyopathy, “broken heart syndrome” or transient left ventricular apical ballooning syndrom is a recently described cardiac condition. TCM is an independent disease entity mimicking the clinical and instrumental presentation of acute coronary syndrome (ACS) in the absence of any evidence of obstructive atherosclerotic coronary artery lesion. Originally described in Japan, this syndrome is characterized by typical clinical and laboratory features of ACS in accordance with transient hypokinesis of the left ventricular apex. TCM occurs more often in postmenopausal elderly women and is associated with emotional or physical stress. In most cases TCM is benign and completely reversible condition. However close resemblance of clinical and instrumental manifistations of TCM to those of ACS is the cause of misdiagnosis at the early stage of the disease. The article presents a brief review of up to date data. TCM is a rare condition in patients with the end-stage renal disease. A case of TCM associated with maintenance hemodialysis is reported to our knowledge reported in the first time. We believe that stress during maintenance hemodialysis led to the TCM occurrence and therefore qualify this as a periprocedural complication.