Introduction: Unlike idiopathic nephrotic syndrome (NS), hereditary podocytopathies are not expected to recur after kidney transplantation. However, some reports of posttransplant recurrence of NS in patients carrying variants in the NPHS2 gene have been described, notably with the p.Arg138Gln variant, which is more prevalent in Europe. The objective of this study was to assess the risk of recurrence after kidney transplantation in a large cohort of patients with biallelic NPHS2 pathogenic variants. Methods: Since January 2010, 61 patients identified at Necker-Enfants Malades Hospital and 56 enrolled in the PodoNet Registry with biallelic variants in the NPHS2 gene were transplanted and were compared with 44 transplanted children with steroid-resistant NS (SRNS) without any identified pathogenic variant. Results: Of the 117 patients, 23 carried the p.Arg138Gln variant in the homozygous state and 16 in the compound heterozygous state. The other 78 patients carried different variants in the homozygous (n = 44) or compound heterozygous state. Only 1 patient with NPHS2-related SRNS experienced posttransplant recurrence (median follow-up of cohort 8.5 years [2.5–15]). Conversely, 7 of 44 patients (16%) without any identified pathogenic variant recurred within a maximum of 7 days after transplantation (median follow-up 8.9 years [0.6–13.9]). Conclusion: In this large cohort, the risk of patients with causative variants in the NPHS2 gene to develop NS recurrence after kidney transplantation was extremely low. This is coherent with the pathophysiology of intrinsic slit-diaphragm disease. These data are reassuring and should be considered when counselling patients, making living kidney donation, whether related or not, a safe choice.

Background. Aging is a multifactorial process defined by an accumulation of damage in all tissues and organs, including the skin, throughout the lifespan of an individual. The reduction of both cellular and extracellular matrix components of the dermis during the aging process is followed by the alteration of the morphology of the skin tissue. This study was conducted to assess skin morphology in men before and 3 months after the intradermal injection of autologous fibroblastic cells.Methods. Tissue biopsies were surgically obtained before and 3 months after the treatment with autogenously harvested fibroblasts expanded in vitro, as well as after injection of phosphate-buffered saline. The thickness of collagen fiber bundles and number of fibroblasts in the dermis were analyzed in morphometric studies. The morphologic evaluation, using different methods of staining has been performed to analyze of extracellular matrix proteins, including collagen and reticular fibers, fibrillin-1-rich microfibrils, elastic fibers, and hyaluronic acid.Results. After administration of the cells, we found a noticeable increase in the number of fibroblasts within the dermis, a significant enlargement in diameter of the collagen fiber bundles, and an improvement in the density of reticular fibers, fibrillin-1-rich microfibrils, and elastic fibers compared with the initial, steady-state condition.Conclusions. The administration of autogenous fibroblasts could be an effective and safe adjunctive therapy to conventional health care treatment to prevent and reduce the age related accumulation of dermal tissue damage.

Pathogenesis of several renal diseases is strongly connected with cytokines. The polymorphism of IL1RN gene exists in intron 2 and is caused by variable number of 86bp sequence repeats. In addition, previous studies confirmed the association of IL1RN*2 with inflammatory diseases, among them glomerulonephritis. Therefore it raises the question whether VNTR polymorphism of IL1RN gene determines the susceptibility to DMP and its clinical course. The study group consisted of 56 children with DMP and 105 healthy children as controls. Genomic DNA was extracted from peripheral blood leukocytes. The IL1RN intron 2 VNTR polymorphism was determined by PCR technique with primers flanking the polymorphic region. Significant differences in genotype (p=0,032) and allele (p=0,045) frequencies were observed between children with DMP and control group. The genotype distribution was as follows: *1/*1 - 48,2%, *1/*2 - 30,4%, *1/*3 - 3,6%, *2/*2 - 14,3%, *3/*3 - 1,8%, *3/*4 - 1,8% in DMP group and *1/*1 - 58,1%, *1/*2 - 36,2%, *1/*3 - 3,8%, *2/*2 - 1,9% in controls. The prevalence of alleles in children with DMP was: *1 - 65,2%, *2 - 29,4%, *3 - 4,5%, *4 - 1,9% while in control group: *1 - 78,1%, *2 - 20%, *3 -1,9%. Additionally IL1RN*2 allele homozygosity showed eight fold higher risk for DMP (OR=8,58; 95%CI, 1,73 to 42,48; p=0,008). No association between IL1RN genotypes and response to steroid therapy or frequency of relapses was observed in the study group. Our results suggest that IL1RN*2 homozygosity predisposes to diffuse mesangial proliferation in Polish children.

Application of molecular biology techniques in investigations of acute lymphoblastic leukemia contributed to better understanding of leukemic transformation mechanisms and allowed more accurate evaluation of treatment efficacy. The idea of residual malignant cells (MRD) has been introduced in order to evaluate more accurately the real number of circulating leukemic cells and to improve the methods of treatment and survival rates [7]. Monoclonal rearrangements of IgH and TCR genes are unique features of the given leukemic clone which allows monitoring of minimal residual disease (MRD) using the method of polymerase chain reaction (PCR). The rearrangements of IgH gene may be used in monitoring of residual leukemic cells in most cases of B-cell acute lymphoblastic leukemia. Majority of MRD studies in ALL were performed exclusively in children [1, 3, 4, 5, 9, 12, 13, 15, 17, 18, 19, 21, 22]. Elimination of residual leukemic cells confirmed by negative results of PCR test may predict long -term event- free survivals [14]. Many reports underline that positive PCR result frequently predicts relapse; however, it should be emphasized, that the result depends mainly on frequency and timing of the studies. The positive PCR results are also associated mainly with the medullary relapse [9,12,15, 17,18,19,22]. It is suggested that quantitative evaluation of MRD is more important than positive result found in a single investigation [16,17]. Some authors believe that evaluation of MRD at the end of the treatment constitute a valuable test for identifying patients likely to relapse [5,6, 13,18]. Other authors underline the lack of predictive value of that test in every single time point, thus indicating the need for serial semi — quantitative studies [16,17].

Abnormalities in chromosomes of malignant cells comprise one of the independent prognostic factors in acute lymphoblastic leukemia in children. Depending on the type of the abnormality, the patients are assigned to the different risk groups [1,3,13]. Studies on isoenzymes and immunological markers provide valuable information on aetiology of ALL; however, the mystery of leukemic transformation or persistent malignancy are not yet cleared. Classification of ALL according to cytogenetic features, both modal and structural, turned out to be more promising approach [9]. The presence of specific cytogenetic abnormalities within leukemic cells prompted molecular studies on the breaking points within the genes and their protein products [15].

The survival rate in children with acute lymphoblastic leukemia (ALL) exceeds 70% with the use of current treatment protocols [11]. However, 30% of ALL patients eventually develop relapses [3]. It is believed that residual leukemic cells that survived despite chemotherapy are responsible for the recurrent leukemia. At presentation of disease patients with ALL have approximately 1012 leukemic cells [7]. After induction therapy at least 95% of all ALL children achieve remission [11]. However, this only means that the number of leukemic cells in bone marrow detected morphologically is below 5%. Approximately 1010 leukemic cells may still be present in patient′s body. Despite satisfactory results of treatment there is still space for survival improvement. One of the methods of therapy adjustment is identification of children who despite classification to the low or moderate risk groups would eventually relapse, and who probably would benefit from the more aggressive treatment. Identification of poor of moderate risk patients who would rather benefit from less aggressive or shorter treament is also a very important problem, since these patients could avoid irreversible sequela or intolerance of the prolonged chemotheraphy. Steroid- resistance detected using morphological criteria in the initial phase of theraphy turned out to be unfavorable prognostic factors with independent prognostic importance [5,8,12,14].

In acute leukemias malignant cells derived from the sole parent cell that underwent neoplastic transformation share identical configuration of Ig and TCR genes. Monoclonal rearrangements of Ig and TCR genes comprise unique features of the given leukemic clone, thus allowing the basis for monitoring of the minimal residual disease (MRD) using polymerase chain reaction (PCR) method in acute lymphoblastic leukemias [1,4,7,14,22]. Results of several clinical studies indicate that detection of residual leukemic cells in ALL correlates positively with relapse [5,10,14,20, 21,22]. Acute T-cell lymphoblastic leukemia is a clinically homogenous disease with high rate of treatment failures. Thus, T-cell immunophenotype is considered as an unfavourable prognostic factor. Intensification of treatment in that group of patients produced current results comparable with those achieved in patients with non- T-ALL [14,15,16]. Occurrence of relapse reflects ineffectiveness of chemotherapy and allogenic bone marrow transplantation is probably the only chance for cure. Ability to identify the population at risk of relapse would allow early alternative treatment. In that context TCRδ and TCRγ gene rearrangements represent the optimal target for monitoring of MRD using PCR assay in patients with T-ALL, since at least one allele is rearranged in 95% of patients and remains stable in more than 90% of cases [3], Also TCRδ gene rearrangements, present in 70% of patients with T-ALL, show limited potential of variety, thus allowing the use of procedures that detect patients with positive results, and vast diversity of junctional sites allows preparation of patient- specific probes [2,3], Studies performed by Dibenedetto et al. showed that residual malignant cell might be detected in PCR test 12-15 weeks after completion of induction therapy in almost all patients (94%), regardless of the therapy protocol [8]. Their analysis confirms the observation that presence of MRD 30-40 weeks after diagnosis is a predictor of poor prognosis. On the contrary, lack of residual leukemic cells in any time point after diagnosis is correlated positively with favourable prognosis. In this prospective study we investigated the group of 18 patients with childhood T-cell ALL in various time points of BFM 90 treatment protocol. We applied the method of polymerase chain reaction previously described by Vandenvelde et al. and Taylor et al. [18,19]. The aim of the study was to answer the question whether the presence of MRD in children with T-ALL might influence the outcome.

Increase of renal expression of transforming growth factor beta 1 (TGF-beta 1) gene caused by activation of the local renin-angiotensin system plays an important role in the pathogenesis of glomerulonephritis (GN). The aim of the present study was to measure the expression of renin and TGF-beta 1 genes (own modification of the RT-PCR method) in the isolated renal glomeruli or in the homogenates of renal biopsy specimens in children with various types of glomerulonephritis. The study enrolled 13 children with glomerulonephritis and 3 boys with Wilm's tumour (control group). The expression of the studied genes was presented using arbitrary units defined as multiplicity of the GAPDH gene. No significant difference was found in expression of mRNA renin in the biopsy specimens of the kidney between GN group and control group. Expression of the TGF-beta 1 gene was found in biopsy specimens in all patients from the control group, and only in one GN child, the sole one who was not treated with converting-enzyme inhibitors. No transcripts of the studied genes were found in all RNA samples obtained from the renal glomeruli using the microdissection method. The RT-PCR method applied in the present study allows evaluation of renal expression of renin and TGF-beta 1 genes. The authors would like to point out that storage of biopsy specimens at -80 degrees C would not prevent the total degradation of RNA during microdissection.

The study group consisted of 24 children with Henoch-Schoenlein purpura (HSP) (13 girls and 11 boys, aged 66-233 months) who were treated in the Ist Pediatric Department between 1980 and 1998. The I/D polymorphism of ACE gene was determined by PCR amplification of genomic DNA with primers flanking the polymorphic region. Our preliminary results suggest lack of association between ACE genotype and kidney function. However, further follow-up studies based on sufficient number of participants are necessary to elucidate the role of ACE polymorphism in appearance and progression of renal symptoms in HSP.

Two cases of hyperglycemia complicating therapy of childhood ALL with the use of L-asparaginase are described. Both patients required insulin administration. The relationship between L-aspa therapy and clinical manifestation of hyperglycemia seems to indicate that this could be the side effects of the drug.

The retrospective analysis was undertaken in order to assess treatment results of childhood ALL achieved in two "independent" units: in Białystok and Szczecin. It comprised 61 patients: 24 girls and 37 boys aged 10 - 197 months (median 64, mean 73 months), who between November 1987 and December 1992 were diagnosed as having ALL. 25 children, with risk factor greater than 0.8 were classified as intermediate risk patients. ALL 61 children were treated greater than 0.8 were classified as intermediate risk patients. ALL 61 children were treated according to BMF 86 protocol modification of the Polish Leukemia Study Group. The observation was closed in February 1993; the follow-up time was within the range of 10 - 72 months (median 32, mean 32 months). 7 patients (11.5%) did not enter remission, 4 children (6.6%) died in remission and 11 children (18.0%) relapsed. The probability of event-free survival (EFS) and disease-free survival (DFS) were 0.53 and 0.67 respectively. There was no statistical difference in p-EFS between standard and intermediate risk patients (SRG = 0.60 vs IRG = 0.53). It has been shown that p-EFS was not statistically influenced by age, sex, WBC, Hb level, paS-positive and acid-positive ALL. It has been suggested that protocol deviations were the main cause of the inferior (as compared to other domestic centers) treatment results.

As reported elsewhere, treatment results in childhood acute lymphoblastic leukemia (ALL) achieved in our institution are still unsatisfactory (T. Urasinski and J. Pogorazelski, unpublished data). After the median follow-up time of 33 months the probability of event-free survival (p-EFS) is 0.429 and relapses are the main reason for treatment failures. Thus the problem of relapsed ALL is of vital importance for us.