Clinicopathologic features of infection-related glomerulonephritis with IgA deposits: a French Nationwide study.

BACKGROUND: Infection-related glomerulonephritis with IgA deposits (IRGN-IgA) is a rare disease but it is increasingly reported in the literature. Data regarding epidemiology and outcome are lacking, especially in Europe. We aimed to assess the clinical, pathologic and outcome data of IRGN-IgA. METHODS: Clinical and outcome data from patients from 11 French centers over the 2007-2017 period were collected retrospectively. We reviewed pathologic patterns and immunofluorescence of renal biopsies and evaluated C4d expression in IRGN-IgA. We analyzed the correlation between histological presentation and outcome. RESULTS: Twenty-seven patients (23 men, mean age: 62 ± 15 years) were included. Twenty-one (78%) had Staphylococcus aureus infection and twelve (44%) were diabetic. At the time of biopsy, 95.2% had haematuria, 48.1% had a serum creatinine level of > 4 mg/dL, and 16% had hypocomplementemia. The most common pathologic presentation included mesangial (88.9%) and endocapillary proliferative glomerulonephritis (88.9%) with interstitial fibrosis and tubular atrophy (IF/TA) (85.1%). Diffuse and global glomerular C4d expression was found in 17.8%, mostly in biopsies with acute or subacute patterns, and was associated with a short delay between infection and renal biopsy compared to segmental and focal staining. After median follow-up of 13.2 months, 23.1% died, 46.2% had persistent renal dysfunction and 15.4% reached end-stage renal disease. Renal outcome was correlated to IF/TA severity. CONCLUSIONS: Infection-related glomerulonephritis with IgA deposits is usually associated with Staphylococcus infections and mainly affects adult men. This entity has a poor prognosis which is correlated to interstitial fibrosis and tubular atrophy severity.

No impact of disseminated intravascular coagulation in kidney donors on long-term kidney transplantation outcome: A multicenter propensity-matched study.

The diagnosis of disseminated intravascular coagulation (DIC) is often considered to be a contraindication to organ donation. The aim of this study was to evaluate the impact of DIC+ donors on kidney recipient (KR) evolution. We identified 169 KRs with DIC+ donation after brain death donors between January 1996 and December 2012 in 6 French transplant centers. Individuals were matched using propensity scores to 338 recipients with DIC- donors according to donor age and sex, whether expanded criteria for the donor existed, graft year, and transplantation center. After kidney transplantation, delayed graft function was observed in 28.1% of DIC+ KRs and in 22.8% of DIC- KRs (NS). Renal allograft survival at 1, 5, and 10 years was 94.5%, 89.3%, and 73.9% and 96.2%, 90.8%, and 81.3% in DIC+ KRs and DIC- KRs, respectively (NS). The median estimated glomerular filtration rate (eGFR) was similar between DIC+ and DIC- KRs at 3 months, 1 year, and 10 years: 45.9 vs 48.1 mL/min, 42.1 vs 43.1 mL/min, and 33.9 vs 38.1 mL/min, respectively. Delayed calcineurin inhibitor introduction or induction had no impact on delayed graft function rate or eGFR evolution at 10 years after transplantation in DIC+ KRs. Donor DIC did not seem to affect initial outcome, long-term graft function, or allograft survival.

Efficacy of eculizumab in an adult patient with HIV-associated hemolytic uremic syndrome: A case report.

INTRODUCTION: Hemolytic uremic syndrome (HUS) in Human Immunodeficiency Virus (HIV)-positive patients has become a rare cause of kidney injury since the era of highly active antiretroviral therapy (HAART). Plasma exchange and antiretroviral therapy were previously recommended but often failed to achieve remission. We report a case of HUS in a HIV-positive patient treated successfully with eculizumab. CASE SUMMARY: A 52-year-old woman presented to hospital with acute renal failure, thrombocytopenia, anemia, and hypoxemia. She had been diagnosed with HIV infection in 1997. Kidney biopsy showed several fibrinous microthrombi in the glomerular capillaries, formation of thrombi in arterioles, moderate parietal and mesangial deposits of C3 and Immunoglobulin M, and intense glomerular and arterial deposits of Complement component 5b9 complement component. Serum HIV viral load was 227,848 copies/mL, and CD4 lymphocyte count was 120 cells/µL. A diagnosis of HIV-associated HUS was made. The patient had no confounding cause of HUS. Initiation of eculizumab and HAART resulted in complete hematological remission on day 32 and dialysis withdrawal on day 110. The patient has not relapsed during long-term follow-up (M17). CONCLUSION: This observation suggests that eculizumab can achieve remission in HIV patients with HUS.

Dendritic cells in chronic mycobacterial granulomas restrict local anti-bacterial T cell response in a murine model.

BACKGROUND: Mycobacterium-induced granulomas are the interface between bacteria and host immune response. During acute infection dendritic cells (DCs) are critical for mycobacterial dissemination and activation of protective T cells. However, their role during chronic infection in the granuloma is poorly understood. METHODOLOGY/PRINCIPAL FINDINGS: We report that an inflammatory subset of murine DCs are present in granulomas induced by Mycobacteria bovis strain Bacillus Calmette-guerin (BCG), and both their location in granulomas and costimulatory molecule expression changes throughout infection. By flow cytometric analysis, we found that CD11c(+) cells in chronic granulomas had lower expression of MHCII and co-stimulatory molecules CD40, CD80 and CD86, and higher expression of inhibitory molecules PD-L1 and PD-L2 compared to CD11c(+) cells from acute granulomas. As a consequence of their phenotype, CD11c(+) cells from chronic lesions were unable to support the reactivation of newly-recruited, antigen 85B-specific CD4(+)IFNgamma(+) T cells or induce an IFNgamma response from naïve T cells in vivo and ex vivo. The mechanism of this inhibition involves the PD-1:PD-L signaling pathway, as ex vivo blockade of PD-L1 and PD-L2 restored the ability of isolated CD11c(+) cells from chronic lesions to stimulate a protective IFNgamma T cell response. CONCLUSIONS/SIGNIFICANCE: Our data suggest that DCs in chronic lesions may facilitate latent infection by down-regulating protective T cell responses, ultimately acting as a shield that promotes mycobacterium survival. This DC shield may explain why mycobacteria are adapted for long-term survival in granulomatous lesions.

[Determination of ethanol concentrations from bile and its importance in forensic medicine]. / Epébol történo etilalkohol meghatározás jelentosége az igazságügyi orvostani gyakorlatban.

Determination of post-mortem ethanol concentration is a very important analytical examination in forensic toxicological daily routine. But in many cases, blood and urine are not available in appropriate quality and quantity for the analysis. In these cases, other biological matrices such as liquor vitreous humor, saliva, bile, etc. can be used for ethanol concentration determination. In toxicological laboratories, these kinds of examinations have been done for decades. In our institute, we compared the ethanol concentrations of blood, urine and bile samples collected from 115 autopsies. Determination of ethanol levels was carried out by using headspace GC according to international practice. The average of ethanol concentration ratios ([blood]/[bile]) was 1,220. Furthermore, we examined the pH of bile samples, but we did not find any relationships between ethanol levels and pH values. In 90 percent of results, positive correlation can be shown between bile and blood ethanol levels. In remaining cases, we tried to account for the reasons of differences by looking into autopsy reports.

Distribution of ghrelin-immunoreactive neuronal networks in the human hypothalamus.

Ghrelin has been discovered as the endogenous ligand of the growth hormone secretagogue receptor (GHS-R). It stimulates growth hormone secretion and also potently increases food intake. To date, ghrelin is the only known peripheral orexigenic hormone. Recent studies have demonstrated that in addition to peripheral organs, ghrelin is also synthesized in the hypothalamus. In the present study, we examined the distribution of the ghrelin-immunoreactive (IR) elements in the human hypothalamus. Ghrelin-IR fibers were widely distributed throughout the hypothalamus. Based on the thickness of fibers, major subtypes of ghrelin-IR axons were observed: thick fibers with large varicosities and very fine axons with or without small varicosities. Dense networks of ghrelin-IR axons were observed in the hypothalamic suprachiasmatic, paraventricular, supraoptic, dorsomedial, ventromedial and infundibular nuclei and in the periventricular area. Ghrelin-IR axons also appeared in the external layer of the pituitary stalk. Ghrelin-IR cell bodies were not detected. Since hypothalamic regions innervated by ghrelin-IR axons also take part in the regulation of food intake and energy balance, the centrally synthesized ghrelin may play a major role in the central regulation of energy metabolism in humans.

Jumping and falling death in children, adolescents, and young adults.

INTRODUCTION: Evaluation of fatal jumps and falls from height in children, adolescents and young adults needs careful medico-legal investigation. The aim of this study was to examine the distribution of undetermined falling from height, accidental falling, and suicidal jumping cases between 1990-2003. METHODS: Copies of death certificates relating to falling from height and jumping deaths in Hungarian youths from the ages of 0-24 years of those resident in Hungary were obtained. RESULTS: 215 (34.1%) accidental falls, 394 (62.6%) suicidal jumping, and 21 (3.3%) undetermined intent were investigated. A significant increase was detected in suicidal jumping death in the age group of 15-19 years (OR=0.7, CI=0.49-0.98, p=0.039), and in the age group of 20-24 years (OR=0.72, CI=0.54-0.96, p=0.025) in the most recent 5 year study period. CONCLUSION: Data concerning the scene investigation, detailed forensic autopsy, and family history have important role in the differentiation of fatal jumping or falling cases. Further investigation about the characteristics injuries may help the final determination of violent death causes at youth, and more effort should be directed to an effective prevention strategy for jumping or falling death cases.