Jaromir Hacek

Nephrotic syndrome and acute kidney injury in a patient treated with lithium carbonate

Lithium carbonate has been used in psychiatry for decades for the treatment of depression and bipolar disorder. However, this medicine has several renal side effects such as nephrogenic diabetes insipidus, chronic tubulointerstitial nephritis, distal renal tubular acidosis and, rarely, nephrotic syndrome (NS).1 In addition, lithium intoxication can also lead to acute kidney injury (AKI).2 The pathogenesis of lithiuminduced NS is not fully understood, and underlying genetic predisposition or idiosyncratic causes are involved.3 The majority of patients recover after discontinuation of lithium treatment. Kidney biopsy usually shows minimal change disease (MCD), although focal segmental glomerulosclerosis has been seen.4

Clinical and cytopathological factors affecting the cellularity of urinary cell blocks and the implication for diagnosis and follow-up of urinary bladder urothelial carcinoma

The methodology of cell blocks (CBs) has long been an integrated part of cytology. However, there are very few data on CBs derived from urine. Their main disadvantage is a lack of cellularity, which limits their broader clinical applicability. Factors affecting cellular adequacy in urine remain unclear. We assessed the impact of basic clinical and cytopathological factors on the adequacy of cellularity in urinary CBs.

Urinary Neutrophil Gelatinase-Associated Lipocalin Does Not Distinguish Acute Rejection from Other Causes of Acute Kidney Injury in Pediatric Renal Transplant Recipients

BACKGROUND The aim of this prospective single center study was to investigate the ability of urinary neutrophil gelatinase-associated lipocalin (NGAL) to distinguish acute rejection from other causes of acute kidney injury (AKI) in children after renal transplantation. METHODS Fifteen children fulfilled the inclusion criteria (acute kidney injury (AKI) with allograft biopsy, at least 21 days after renal transplantation, no sepsis) during 2013 - 2014 in our pediatric transplantation center. The mean age was 14.8  2.8, median time after renal transplantation was 0.4 years (range 0.1 - 3.8). Urinary NGAL was measured in spot urine by Chemiluminescent Microparticle Immunoassay technology. RESULTS Four patients had biopsy proven acute rejection (rejection group), eleven children had AKI of other cause (non-rejection group). The median urinary NGAL concentration in the rejection group was not significantly different from NGAL in the non-rejection group (7.3 ng/mL, range 3.0 - 42.3 vs. 8.6 ng/mL, range 3.4 - 54.7, p = 0.48). There was a significant negative correlation between eGFR and urinary NGAL concentrations (r = -0.77, p < 0.001). CONCLUSIONS Our small study suggests that in children after renal transplantation, urinary NGAL cannot be used as a specific marker for distinguishing acute rejection from other non-rejection causes of AKI. Urinary NGAL was mainly associated with graft function but not with the etiology of AKI.

AB0599 Interleukin-35 in Idiopathic Inflammatory Myopathies

Background Interleukin-35 (IL-35) is a newly described heterodimeric cytokine that belongs to the IL-12 family and consists of p35 (IL-12a) and EBI3 (IL-27b) subunits. IL-35 exerts immunomodulatory activities in several autoimmune inflammatory diseases. Objectives The aim of this study was to assess IL-35 expression in muscle tissue of patients with idiopathic inflammatory myopathies (IIM) and to compare serum levels of IL-35 in patients with IIM to healthy controls and asses potential association with activity of IIM. Methods The expression of IL-35 was studied in a series of 19 muscle biopsy samples of idiopathic inflammatory myopathies (9 dermatomyositis, 10 polymyositis) and 10 non-inflammatory control muscle biopsies from patients with myasthenia gravis.Serum levels of IL-35 were measured in 23 PM, 28 DM and 15 cancer associated myositis patients as well as in 40 healthy controls.Disease activity was evaluated by the Myositis Disease Activity Assessment Tool (MYOACT) and by serum muscle enzymes. Results Both IL-35 subunits were found in immune cells of the inflammatory infiltrates in IIM muscle biopsies, no immunoreactivity was observed in muscle tissue of control patients.IL-35 serum levels were increased in all IIM patients compared to healthy controls (p<0.001). There were no differences in IL-35 serum levels between myositis subgroups. Serum IL-35 levels correlated with the overall MYOACT score, with extramuscular and muscle domains of MYOACT, with physicians global activity assessment and lactate dehydrogenase levels. Conclusions IL-35 subunits are overexpressed in inflammatory infiltrates in muscle tissue of IIM patients and elevated circulating IL-35 levels correlate with several disease activity parameters. These data suggest potential role of IL-35 in the pathogenesis of inflammatory myopathies. Acknowledgement Supported by MHCR support for conceptual development of a research organization (023728) and BTCure (115142–2). Disclosure of Interest None declared

Oral penicillin-associated acute kidney injury in an infant with acute pyelonephritis.

Beta‐lactam‐associated acute tubulointerstitial nephritis (ATIN) is a rare condition in childhood. We report the case of an infant with penicillin‐associated ATIN and concomitant acute pyelonephritis resulting in the development of severe acute kidney injury (AKI). The treatment consisted of penicillin suspension and appropriate AKI management, which required a short period of dialysis. Finally, full recovery and normalization of laboratory parameters occurred. We present here the first case of oral penicillin‐associated ATIN in childhood.

Idiopathic inflammatory myopathies – potential role of the immunoexpression of interleukin-35 in muscle biopsy and peripheral blood mononuclear cells

Background: Interleukin-35 (IL-35) is a newly described heterodimeric cytokine of the IL-12 family. Studies of immunopathogenesis in idiopathic inflammatory myopathies (IIM) are of interest for future biological therapies. Objective: To analyze expression of IL-35 in muscle biopsies and to study its effects on peripheral blood mononuclear cells (PBMC) in vitro to assess its pathogenetic and diagnostic value. Materials and methods: Immunoexpression of IL-35 subunits (p35, EBI3) was studied immunohistochemically in 23 muscle biopsies of IIM (12 dermatomyositis, 11 polymyositis), 10 non-inflammatory myopathies and 10 controls. PBMCs were stimulated with human recombinant IL-35 protein or TNF-&agr; in vitro. Taq-Man RT-PCR was performed to analyze gene expression after 6 hours and ELISA assays were used to confirm the protein secretion after 24 hours of stimulation. Results: We showed localization of both IL-35 subunits in B-cells, T-cells and macrophages of the inflammatory infiltrates in IIM. No immunoreactivity was observed in controls. We found that gene expression of both IL-35 subunits were dose- and time-dependently induced by TNF-&agr; in PBMCs. Conclusion: Our data suggest pro-inflammatory properties of IL-35 and its potential role in the pathogenesis of IIM. The immunohistochemical expression of IL-35 might be also of diagnostic help in muscle biopsy.

Surprisingly favorable outcome in a patient with Goodpasture's disease

1 Minnaganti VR, Cunha BA. Infections associated with uremia and dialysis. Infect Dis Clin North Am. 2001; 15:385–406. 2 Hauser AB, Stinghen AEM, Kato S et al. Characteristics and causes of immune dysfunction related to uremia and dialysis. Perit Dial Int. 2008; 28:S183–S187. 3 Diaz-Lagares C, Peter-Alverez R, Garcia-Hernandez FJ et al. Rates of and risk factors for severe infections in patients with systemic autoimmune diseases receiving biological agents off-label. Arthritis Res Ther. 2011; 13: R112. 4 Galloway JB, Hyrich KL, Mercer LK et al. Risk of septic arthritis in patients with rheumatoid arthritis and the effect of anti-TNF therapy: Results from British Society for Rheumatology Biologics Register. Ann Rheum Dis. 2011; 70:1810–1814. 5 Don BR, Spin G, Nestorov I, Hutmacher M, Rose A, Kaysen GA. The pharmacokinetics of etanercept in patients with end-stage renal disease on hemodialysis. J Pharm Pharmacol. 2005; 57:1407–1413. 6 Sign R, Cuchacovich R, Huang W, Epinoza LR. Infliximab treatment in a patient with rheumatoid arthritis on hemodialysis. J Rheumatol. 2002; 29:636–637. 7 Hammoudeh M. Infliximab treatment in a patient with rheumatoid arthritis on hemodialysis. Rheumatology. 2006; 45:357–359. 8 Iwamoto M, Honma S, Asano Y, Minota S. Effective and safe administration of tocilizumab to a patient with rheumatoid arthritis on hemodialysis. Rheumatol Int. 2011; 31:559–560. 9 Sugioka Y, Inui K, Koike T. Use of etanercept in a patient with rheumatoid arthritis on hemodialysis. Mod Rheumatol. 2008; 18:293–295. 10 Senel S, Kisacik B, Ugan Y, Kasifoglu T, Tunc E, Cobankara V. The efficacy and safety of etanercept in patients with rheumatoid arthritis and spondyloarthropathy on hemodialysis. Clin Rheumatol. 2011; 30:1369–1372. 11 Nakamura T, Higashi S, Tomoda K, Tsukano M, Baba S. Efficacy of etanercept in patients with AA amyloidosis secondary to rheumatoid arthritis. Clin Exp Rheumatol. 2007; 25:518–522. 12 Nakamura T, Higashi S, Tomoda K, Tsukano M, Arizono K, Nakamura T. Etanercept treatment in patients with rheumatoid arthritis on hemodialysis. Rheumatol Int. 2010; 30:1527–1528.