The Outcome of Childhood Immunoglobulin A Nephropathy with Acute Kidney Injury at the Onset of the Disease-National Study.

Introduction: IgA nephropathy (IgAN) is the most common glomerulonephritis worldwide. Decreased glomerular filtration rate is a known risk factor for disease progression. Aim: We aimed to examine factors that may contribute to disease progression in children that present with impaired eGFR at the onset of IgAN. Materials and methods: Of the 175 patients with IgAN from the Polish Registry of Children with IgAN and IgAVN, 54 (31%) patients with IgAN who had an onset of renal function impairment (GFR < 90 mL/min) were eligible for the study. All of them were analyzed for initial symptoms (GFR according to Schwartz formula, creatinine, proteinuria, IgA, C3), renal biopsy result with assessment by Oxford classification, treatment used (R-renoprotection, P-prednisone+R, Aza-azathioprine+P+R, Cyc-cyclophosphamide+P+R, CsA-cyclosporine+P+R, MMF-mycophenolate mofetil+P+R), and distant follow-up. Based on the GFR score obtained at the end, patients were divided into two groups: A-GFR > 90 mL/min and B-GFR < 90 mL/min. Results: In the study group, the mean age of onset was 12.87 ± 3.57 years, GFR was 66.1 ± 17.3 mL/min, and proteinuria was 18.1 (0-967) mg/kg/d. Renal biopsy was performed 0.2 (0-7) years after the onset of the disease, and MESTC score averaged 2.57 ± 1.6. Treatment was R only in 39% of children, P+R in 20%, Aza+P+R in 28%, Cyc+P+R in 9%, CsA+P+R in 7%, and MMF+P+R in 3%. The length of the observation period was 2.16 (0.05-11) years. At the follow-up, Group A had 30 patients (56%) and Group B had 24 patients (44%). There were no significant differences in any of the other biochemical parameters (except creatinine) or proteinuria values between the groups and the frequency of the MESTC score ≥ 2 and <2 was not significantly different between Groups A and B. Patients with normal GFR at the follow-up (Group A) were significantly more likely to have received prednisone and/or immunosuppressive treatment than those in Group B (p < 0.05) Conclusions: In a population of Polish children with IgAN and decreased renal function at the onset of the disease, 56% had normal GFR in remote observation. The use of immunosuppressive/corticosteroids treatment in children with IgAN and impaired glomerular filtration rate at the beginning of the disease may contribute to the normalization of GFR in the outcome, although this requires confirmation in a larger group of pediatric patients.

Advanced microscopy analysis of the micro-nanoscale architecture of human menisci.

The complex inhomogeneous architecture of the human meniscal tissue at the micro and nano scale in the absence of artefacts introduced by sample treatments has not yet been fully revealed. The knowledge of the internal structure organization is essential to understand the mechanical functionality of the meniscus and its relationship with the tissue's complex structure. In this work, we investigated human meniscal tissue structure using up-to-date non-invasive imaging techniques, based on multiphoton fluorescence and quantitative second harmonic generation microscopy complemented with Environmental Scanning Electron Microscopy measurements. Observations on 50 meniscal samples extracted from 6 human menisci (3 lateral and 3 medial) revealed fundamental features of structural morphology and allowed us to quantitatively describe the 3D organisation of elastin and collagen fibres bundles. 3D regular waves of collagen bundles are arranged in "honeycomb-like" cells that are comprised of pores surrounded by the collagen and elastin network at the micro-scale. This type of arrangement propagates from macro to the nanoscale.

IgA Nephropathy in Children: A Multicenter Study in Poland.

IgA nephropathy (IgAN) is the most common form of glomerulonephritis in pediatric population. The clinical presentation of the disease in children ranges from microscopic hematuria to end-stage kidney disease. The aim of the study was to retrospectively assess clinical and kidney biopsy features in children with IgAN. We assessed a cohort of 140 children, 88 boys, 52 girls with the diagnosis of IgAN in the period of 2000-2015, entered into the national Polish pediatric IgAN registry. The assessment included the following: proteinuria, hematuria, glomerular filtration rate (GFR), arterial blood pressure, and the renal pathological changes according to the Oxford classification and crescents formation, as modifiable and unmodifiable risk factors. The incidence of IgAN in Poland was set at 9.3 new cases per year. The mean age at onset of IgAN was 11.9 ± 4.3 years, and the most common presentation of the disease was the nephritic syndrome, recognized in 52 % of patients. Kidney biopsy was performed, on average, 1.3 ± 2.0 years after onset of disease. Based on the ROC analysis, a cut-off age at onset of disease for GFR <90 mL/min/1.73 m2 (risk factor of progression) was calculated as 13.9 years. Unmodifiable lesions: segmental sclerosis, tubular atrophy/interstitial fibrosis (S1, T1-2) in the Oxford classification and crescents in kidney biopsy were significantly more common in Gr 1 (>13.9 years) compared with Gr 2 (<13.9 years), despite a significantly shorter time to kidney biopsy in the former. We conclude that IgAN in children may be an insidious disease. A regular urine analysis, especially after respiratory tract infections, seems the best way for an early detection of the disease.

[Platelet activation in relapse idiopathic nephrotic syndrome in children]. / Aktywacja plytek krwi w zaostrzeniu idiopatycznego zespolu nerczycowego u dzieci.

The role that platelets play in pathogenesis and thromboembolic complications of the idiopathic nephrotic syndrome (INS) in children still remains unclear. The aim of the study was to analyse of platelet activation in whole blood during first 8 weeks of ins. Study group comprised 24 children with 34 relapses of INS by ISKDC (group A). Obtained results were compared to 16 healthy children (group B). We assessed activation by the count of platelet aggregates, microparticles and surface expression of selected markers--CD62P (P-selectin), CD42b (part of von Willebrand factor receptor) at the onset INS, after 2 weeks of therapy. We found the increased counts of platelet aggregates and microparticles at the onset of INS with a systematic decrease in following 2 weeks. Furthermore, expression of CD42b was significantly lower at the beginning of therapy. There were no clear correlation between markers of activation and biochemical parameters in the study group. According to these findings we conclude that increased activation of blood platelets is an independent risk factor of thromboembolic complication in the early stages of relapse of INS. The role of platelets in pathogenesis or induction of ins relapse remains the matter for further investigation.

[Congenital hyperammonemia in neonates treated with hemodiafiltration]. / Hiperamonemia wrodzona u noworodków leczonych z zastosowaniem hemodiafiltracji.

Inborn defects of urea cycle often results in life-threatening hyperammonemia in neonates. The initial therapy of this disease comprises administration of benzoate sodium, arginine, lactulose, neomycin, and restrictive alimentation based on carbohydrates. Renal replacement therapy for ammonia removal should be considered for the most severe cases. We present a case report of two neonates with very rare inborn urea cycle disorders--deficiency of argininosuccinate lyase and carbamyl-phosphate synthetase, treated with spontaneous arterio-venous haemodiafiltration.

SOS mutator activity: unequal mutagenesis on leading and lagging strands.

A major pathway of mutagenesis in Escherichia coli is mediated by the inducible SOS response. Current models of SOS mutagenesis invoke the interaction of RecA and UmuD'(2)C proteins with a stalled DNA replication complex at sites of DNA lesions or poorly extendable terminal mismatches, resulting in an (error-prone) continuation of DNA synthesis. The precise mechanisms of SOS-mediated lesion bypass or mismatch extension are not known. Here, we have studied mutagenesis on the E. coli chromosome in recA730 strains. In recA730 strains, the SOS system is expressed constitutively, resulting in a spontaneous mutator effect (SOS mutator) because of reduced replication fidelity. We investigated whether during SOS mutator activity replication fidelity might be altered differentially in the leading and lagging strand of replication. Pairs of recA730 strains were constructed differing in the orientation of the lac operon relative to the origin of replication. The strains were also mismatch-repair defective (mutL) to facilitate scoring of replication errors. Within each pair, a given lac sequence is replicated by the leading-strand machinery in one orientation and by the lagging-strand machinery in the other orientation. Measurements of defined lac mutant frequencies in such pairs revealed large differences between the two orientations. Furthermore, in all cases, the frequency bias was the opposite of that seen in normal cells. We suggest that, for the lacZ target used in this study, SOS mutator activity operates with very different efficiency in the two strands. Specifically, the lagging strand of replication appears most susceptible to the SOS mutator effect.

[Metabolic disorders in children with urolithiasis]. / Zaburzenia metaboliczne u dzieci ze skapoobjawowa postacia kamicy dróg moczowych.

Nephrolithiasis is a common disease of multifactorial ethiopatogenesis. The majority of stone formers has disturbances in the metabolism and excretion of stone constituents, promotors or inhibitors of crystallization. The aim of our study was to evaluate metabolic disturbances in children with nephrolithiasis in the early stages of the disease. Cases with severe urinary obstruction, infection and glomerular filtration decrease were excluded. Daily calcium, uric acid, oxalate, phosphate, sodium, potassium, chloride, citrate, and magnesium excretion was examined in 27 children (12 M, 15 F, mean age--10.4 +/- 3.9 y). Hypercalciuria (10 cases) and hiperurykosuria (8 cases) were most often found in the studied group. We concluded that early diagnosis of metabolic background of stone formation (promotors and inhibitors) enables to apply proper preventive measures.

[Activation of coagulation cascade in children during an idiopathic nephrotic syndrome relapse]. / Aktywacja ukladu krzepniecia u dzieci w trakcie rzutu idiopatycznego zespolu nerczycowego.

UNLABELLED: The objective of this study was to assess concentrations of selected markers of coagulation in children with relapse of idiopathic nephrotic syndrome during a 6-week therapy. Study groups: 22 subjects (32 relapses)--14 males, 8 females (mean age 7.15 +/- 1.5 y.) with no thrombotic complications were included into the study. All children were clinically steroid-sensitive. METHODS: Coagulation markers (platelet count, thrombin time, APTT, INR, fibrinogen 1 + 2 fragments (F1 + 2), thrombin-antithrombin complexes (TAT), serum levels of D-dimer (DD), fibrin monomers (FM) and antithrombin activity (ATIII)) were measured three times: on admission, after 2 and 6 weeks. The control group consisted of 13 healthy children. RESULTS: Serum concentration of TAT or F1 + 2 did not differ between 3 stages (p > 0.05). However, values at 0 and 2 weeks were significantly higher than in control group (p < 0.05). We found no correlation between TAT or F1 + 2 and FBG, ALB, TCH, TG levels. [table: see text] CONCLUSIONS: The coagulation cascade in relapse of NS was activated during first 6 weeks of therapy whereas metabolic disturbances (low ALB, high FGB, TCH, TG, high platelets) normalized. It is speculative whether it was caused by active immunological process but definitely it resulted in "prothrombotic state" in INS patients.

Unequal fidelity of leading strand and lagging strand DNA replication on the Escherichia coli chromosome.

We have investigated the question whether during chromosomal DNA replication in Escherichia coli the two DNA strands may be replicated with differential accuracy. This possibility of differential replication fidelity arises from the distinct modes of replication in the two strands, one strand (the leading strand) being synthesized continuously, the other (the lagging strand) discontinuously in the form of short Okazaki fragments. We have constructed a series of lacZ strains in which the lac operon is inserted into the bacterial chromosome in the two possible orientations with regard to the chromosomal replication origin oriC. Measurement of lac reversion frequencies for the two orientations, under conditions in which mutations reflect replication errors, revealed distinct differences in mutability between the two orientations. As gene inversion causes a switching of leading and lagging strands, these findings indicate that leading and lagging strand replication have differential fidelity. Analysis of the possible mispairs underlying each specific base pair substitution suggests that the lagging strand replication on the E. coli chromosome may be more accurate than leading strand replication.

O(-•) chemical ionization of carbonyl compounds.

The negative ion chemical ionization mass spectra of twentyeight C4 to C7 carbonyl compounds were recorded using the oxide radical anion O(-•) as reagent ion. As noted earlier, the reactions occurring include H(+) abstraction, H 2 (+•) abstraction, H- atom displacement, and alkyl radical displacement. In addition, the [M-2H](-) ions fragment further by alkyl radical elimination. The relative importance of these reactions depends strongly on molecular structure, with the result that isomer distinction frequently is possible. Where this is not possible, as for isomeric aldehydes, the collisional charge inversion mass spectra of common product ions provides isomer distinction. The H 2 (+•) abstraction reaction is shown to involve abstraction not only of two hydrogens from the same α-carbon but also, in part, abstraction of one hydrogen from each α-carbon.