Here we present a set of materials tackling the most important aspects of pregnancy management in women with CKD. Three articles, publicized in this issue of "Nephrology and Dilaysis" journal, follow the theme of WKD 2018 campaign "Kidneys and Women's health". Preconception counseling and pregnancy management in women with CKD represent a multidisciplinary problem, and nephrologists, as well as obstetricians, should play a leading role, defi ning both preconception measures and treatment strategies during pregnancy to ensure better outcomes. The authors of presented articles are recognized experts, successfully demonstrated in the real practice high effi cacy of cooperation between nephrologists and obstetricians. Their papers cover such important issues as urinary tract infections, anemia, and mineral-bone disorders in pregnant women with CKD. We strongly hope that these materials will meet the demands of the audience and become an important source of knowledge in the fi eld of reproductive health of women with kidney diseases, which actually raise growing interest worldwide

Pregnant women with chronic kidney disease (CKD) are at risk of developing of urinary tract infection (UTI) due to the presence of additional risk factors. In these women, true bacteriuria was found equally frequent at all stages of CKD, in those with chronic pyelonephritis in 70% of cases, in patients with chronic glomerulonephritis in 45% of cases (p=0.02). According to the results of the national multicenter study "DARMIS", the intestinal pathogen of UTI in pregnant women with CKD is E. coli, characterized by multiple resistance to antibacterial drugs, as well as a high frequency of regional detection of strains with production of beta-lactamases of the extended spectrum of action - 9.6% as a whole in Russia, 25% in the Moscow region. UTI in pregnant women with CKD occurs in the form of: (1) asymptomatic bacteriuria, (2) acute cystitis; (3) acute pyelonephritis in patients with glomerular pathology, (4) exacerbation of chronic pyelonephritis, including renal transplant. The influence of the nature of primary renal disease on clinical symptoms, the tendency to recurrence and generalization of the infectious inflammatory process in urinary tract in pregnant women with asymptomatic bacteriuria, exacerbation of chronic and obstructive pyelonephritis are discussed. Diagnostic criteria in pregnant women with UTI are discussed. Modern approaches to the tactics of antibiotic therapy and prevention are presented in accordance with national and international recommendations, the structure of pathogens, the peculiarities of the clinical course, and kidney function. Pregnant women with CKD who underwent UTI have a high risk of giving birth to premature babies who were required to carry out artificial lung ventilation and transfer to stage nursing.

The review is devoted to the problem of calcium and magnesium homeostasis and its regulation in the human body. Taking into account the latest achievements of molecular biology, the process of passive and active transport of Ca2+ and Mg2+ in the intestine, bones and renal tubules is considered. The role of claudine in the transport of divalent cations in the thick ascending limb of the Henle loop is discussed. The peculiarities of the topology of claudins are considered, which determine the functioning of dense intercellular contacts in the renal tubules and their significance for the process of paracellular reabsorption of Ca2+ and Mg2+. The role of the TRP family channels in the reabsorption of Ca2+ and Mg2+ in the distal nephron is described. The special role of TRPV5 and TRPV6 channels in the active transcellular transfer of these cations, which is of great importance in the regulation of calcium and magnesium homeostasis, is emphasized. Modern views on the role of calcium-sensitive receptors in the regulation of the extracellular level of divalent cations are given. Issues of regulation of renal transport of Ca2+ and Mg2+ are discussed.

The review highlights the issues of changes in the calcium and magnesium homeostasis expressed in the development of hyper- and hypocalcaemia, as well as hypomagnesaemia. The features of primary hyperparathyroidism, malignant hypercalcaemia, and vitamin D intoxication are discussed. Special attention is paid the approaches of modern molecular biology to etiology and pathogenesis of syndrome and non-syndrome forms of hereditary hypercalcaemia, such as multiple endocrine neoplasia, familial hypocalciuric hypercalcaemia, neonatal severe primary hyperparathyroidism; manifestations of hypocalcemia in the form of autosomal dominant hypocalcemia and Bartter syndrome type V; as well as hereditary manifestations of hypomagnesemia as hypomagnesemia with secondary hypocalciuria, family hypomagnesemia with hypercalciuria and nephrocalcinosis, isolated dominant hypomagnesemia with hypocalciuria, Gitelman syndrome. Modern principles and methods of correction of hypercalcemia and hypomagnesemia are discussed.

Aim: to determine the incidence and clinical features of anemia in women with chronic kidney disease (CKD) during pregnancy and postpartum period and the effect of anemia on pregnancy outcomes in women with CKD. Methods: 290 pregnant women with CKD 1-5 stages (age 29.4±5.01 years) and disease duration 12.0 [6.0; 20.5] years, observed in 2011-2017, and 19 healthy pregnancies (age 29.54 ± 4.35 years) were included to the study. During pregnancy and in puerperium clinical blood test was taken and serum creatinine, albumin, fibrinogen, C-reactive protein, serum iron, ferritin, soluble transferrin receptors, folates and erythropoietin were studied. Results: anemia was detected in 36.8% of healthy pregnant women, in 36.0% of women with CKD stage 1, in 50.0% of women with CKD 2, 78.7% in women with CKD3A, 83.3% in women with CKD 3B, 85.7% in women with CKD 4, and in 100% of those with CKD stage 5. Severe anemia occurred only in CKD 3-5 with a frequency of 7.4%. The lowest values of hemoglobin level were observed in women with CKD 3-5 in the postpartum period - 86 [77;101.5] g/l. In patients with anemia, the mean hemoglobin content in erythrocyte, levels of transferrin and albumin were significantly lower, and erythrocyte size heterogeneity coefficient and ferritin level were higher. In CKD pregnant women there was no correlation between hemoglobin and erythropoietin levels. A significant positive correlation of hemoglobin level with terms of delivery and the Quetelet index was revealed in all trimesters of pregnancy. Conclusion: anemia is common in CKD pregnant women, develops due to erythropoietin deficiency, in part due to iron deficiency and systemic inflammation, and has adverse effect on pregnancy outcomes.

Objective: to estimate the state and the rate of bone metabolism in women with chronic kidney disease (CKD) 1-3 stages during pregnancy. Materials and methods: observational cross-sectional and prospective study included 137 pregnant women. CKD 1-3 stage had 85 of them: 64 with CKD 1-2 stage, 21 with CKD 3 stage. Median age 29 years, second and third trimester (42 and 37, respectively). The comparison group consisted of 52 pregnant women with of the same age and gestational age without CKD. Dynamic examination was carried out in 18 cases with CKD 1-3 stage. Ionized, total calcium and inorganic phosphorus, 25-OH vitamin D, parathyroid hormone (PTH), the activity of total alkaline phosphatase (ALP), osteocalcin (OC), N-terminal propeptid of type 1 procollagen (P1NP) and β-isomer of C-terminal telopeptide of type I collagen (β-CTX) were determined. Results: serum calcium, phosphorus and PTH levels in all the examined pregnant women were within their normal range. In pregnant with CKD 3 stage, a deficiency of vitamin D was more significant (р<0.02) compared to pregnant women without CKD and pregnant with CKD 1-2 stage. The levels OC and P1NP and β-CTX in pregnant with CKD 3 stage were higher than in the control group and pregnant women with CKD 1-2 stage. It was also higher in pregnant women with CKD 1-3 stages in the third trimester in comparison with the second one, although remained within the limits of reference values. Significant direct correlations were found between serum concentrations of P1NP and OC (r=0.575, р<0.001), P1NP and ALP (r=0.415, р=0.001), OC and ALP (r=0.276, р=0, 02) and vitamin D and PTH (r=0.235, р=0.04). A significant inverse correlation was found between the blood levels of vitamin D and P1NP (r=-0.344, р=0.002). Conclusions: the peculiarities of bone metabolism in pregnant with CKD of 3 stage are manifested by the vitamin D deficiency and the acceleration of bone formation and resorption to a greater extent in the third trimester.

We present a clinical case of a 34 years old female patient who simultaneously developed two rare conditions: microscopic polyangiitis and atypical hemolytic uremic syndrome (aHUS) associated with a polymorphism in diacylglycerol kinase-ε gene (DGKE), which seems to be the first case of aHUS associated with DGKE mutation in an adult patient. We suggest that the patient experienced chronic subclinical course of thrombotic microangiopathy (TMA) since adolescence, because persistent proteinuria and slowly progressive chronic kidney disease were first found when she was at the age of 13. She developed ANCA-associated vasculitis at the age of 34 with dialysis-dependent renal failure and alveolar hemorrhage that were accompanied by an acute episode of TMA. Treatment with high-dose of corticosteroids, cyclophosphamide and plasmapheresis was initiated. Alveolar hemorrhage have been resolved. However, severe hypertension, hemolytic anemia and thrombocytopenia persisted despite treatment. Plasma resistance was considered to be an indication for treatment with eculizumab, which proved to be beneficial. However, kidney function did not recover. Possible interactions between complement system, DGKE and their possible role in the pathogenesis of TMA are discussed

Nephropathy associated with a mutation in mucin 1 coding gene, a rare hereditary kidney disease characterized by an autosomal dominant type of inheritance, minor changes in urine analysis, development of tubular atrophy and interstitial fibrosis, a slow progressive decrease in renal function. In 2014 at a KDIGO conference, this disease, together with some others having similar clinical and morphological features, was grouped under the common name of autosomal dominant tubulointerstitial kidney disease. Kidney biopsy is not of great importance for the diagnosis of this disease. The only currently known mutation is a single cytosine insertion into a string of 7 cytosines in the variable-number tandem repeat (VNTR) region of the MUC-1 gene. This mutation cannot be detected either by sequencing by Sanger or by a new generation sequencing and is determined by a specially developed method of genetic analysis. We report a case of a 13-year-old girl with a strong family history of chronic kidney disease who was tested positive for the MUC1 mutation.

Porphyria cutanea tarda (PCT) and pseudoporphyria are most frequent photosensitive vesiculobullous skin disorder in hemodialysis patients. PCT is a disorder in the heme biosynthesis that results from a reduction in the activity of the hepatic enzyme uroporphyrinogen decarboxylase (URO-D). The abnormal heme biosynthesis produces a pathogenic accumulation of intermediary metabolites (porphyrins) in the liver, plasma and skin. The symptoms of PCT occur because of the accumulation of photosensitizing porphyrins in the skin. In patients receiving dialysis, PCT has several linked pathogenic mechanisms. The most relevant factors are viral hepatitis C, hepatic iron overload and impaired clearance of porphyrins. Diagnosis of PCT is established by identification of characteristic symptoms and finding a substantial elevation in the level of porphyrins in plasma; fecal porphyrins are also increased. Primary management of PCT involves removing susceptibility factors, depletion of iron stores, and reducing porphyrin levels in the liver and blood. We report a case of PCT that developed in a patient on maintenance HD for 8.5 years; 2 more exacerbations were observed in the next 7.5 years. The diagnosis of PCT was confirmed by the detection of a substantial elevation of porphyrins in plasma. The relationship between exacerbations with viral hepatitis C activity, iron levels was not always observed. Because of comorbidity, therapeutic phlebotomy was problematic and treatment modality was combination of hydroxychloroquine and haemodiafiltration.