Mary Had a Little Ram

The Spanish Mission to Dra Abu el-Naga (Proyecto Djehuty) has been working in the Eighteenth Dynasty Theban Tombs of Djehuty (TT 11) and Hery (TT 12) and their environs since 2002. The excavators uncovered a deposit west of the courtyard of TT 11, consisting of a wrapped ram, a wooden coffin, and a dense deposit of pottery sherds. This is possibly one of the earliest excavated animal burials in the Theban area, and unusual in the fact that it is of a ram. This article focuses on exploring and contextualising this rare find of the late Second Intermediate Period/early New Kingdom.

Relationship between IgA Nephropathy and Porphyromonas gingivalis; Red Complex of Periodontopathic Bacterial Species

IgA nephropathy (IgAN) has been considered to have a relationship with infection in the tonsil, because IgAN patients often manifest macro hematuria just after tonsillitis. In terms of oral-area infection, the red complex of periodontal bacteria (Porphyromonas gingivalis (P. gingivalis), Treponema denticol (T. denticola) and Tannerella forsythia (T. forsythia)) is important, but the relationship between these bacteria and IgAN remains unknown. In this study, the prevalence of the red complex of periodontal bacteria in tonsil was compared between IgAN and tonsillitis patients. The pathogenicity of IgAN induced by P. gingivalis was confirmed by the mice model treated with this bacterium. The prevalence of P. gingivalis and T. forsythia in IgAN patients was significantly higher than that in tonsillitis patients (p < 0.001 and p < 0.05, respectively). A total of 92% of tonsillitis patients were free from red complex bacteria, while only 48% of IgAN patients had any of these bacteria. Nasal administration of P. gingivalis in mice caused mesangial proliferation (p < 0.05 at days 28a nd 42; p < 0.01 at days 14 and 56) and IgA deposition (p < 0.001 at day 42 and 56 after administration). Scanning-electron-microscopic observation revealed that a high-density Electron-Dense Deposit was widely distributed in the mesangial region in the mice kidneys treated with P. gingivalis. These findings suggest that P. gingivalis is involved in the pathogenesis of IgAN.

The Prevalence of Mesangial Electron-Dense Deposits in PLA2R-Positive Membranous Nephropathy

<b><i>Introduction:</i></b> Membranous nephropathy (MN) is a common cause of nephrotic syndrome in adults and can be primary or secondary. The antigenic target of antibodies in 70% of primary cases is phospholipase A2 receptor (PLA2R). The presence or absence of mesangial electron-dense deposits has been used to distinguish between primary and secondary MN. Mesangial deposits suggest MN due to lupus, infection, or other causes, though they are reported to occur in approximately 10% of primary MN. Staining for PLA2R is now frequently used for confirming a diagnosis of primary MN. If mesangial deposits predict a secondary cause, they should be more frequent in PLA2R-negative biopsies. <b><i>Methods:</i></b> A review of institutional kidney biopsies between March 2017 and June 2020 identified all cases of MN. Cases with a diagnosis of lupus or near “full-house” staining by immunofluorescence microscopy (IF) were excluded. Light microscopy, IF, and electron microscopy (EM) were performed. PLA2R staining was performed by IF. EM for all cases was reviewed and electron-dense deposit location, distribution, and size were determined. <b><i>Results:</i></b> Ninety-three cases of MN were identified, of which 86 had both PLA2R staining and EM performed. Of these, 51 cases (59%) were positive for PLA2R and 35 (41%) were negative. Mesangial electron-dense deposits were present in 22 (25.6%) of the 86 cases, including 27.5% (14/51) of PLA2R-positive cases and 22.8% (8/35) of PLA2R-negative cases. No difference was seen in size or distribution of deposits, or other features considered suggestive of secondary MN. <b><i>Conclusion:</i></b> PLA2R-negative cases were not more likely to have mesangial deposits than PLA2R-positive cases. Mesangial deposits should not be used as an indicator of secondary MN.

Clinical and morphological presentation of C3 glomerulopathy: a single-center study of 60 cases

INTRODUCTION. СЗ-glomerulopathy (СЗ-GP) is a spectrum of diseases caused by dysregulation of the alternative complement pathway. The present study was carried out taking into account the limited number of foreign and the absence of original studies in the Russian population.THE AIM. Analysis of clinical and morphological manifestations of СЗ-GP at the time of primary diagnosis.PATIENTS AND METHODS. Retrospective analysis of the etiology, clinical data and morphology of СЗ-GP identified in the period 2006-2021.RESULTS. The study included 60 cases. The average age of patients is 4З±17 years. Nephrotic syndrome was detected in 47 % of patients; in 58 % of cases the estimated glomerular filtration rate was <60 ml/ min/иЗ m2. The dominant morphological pattern was membranoproliferative glomerulonephritis (75% cases). In 2 cases, СЗ-GP debuted with clinical and morphological manifestations of the disease of minimal changes, in which the identification of characteristic electron-dense deposits became obvious when performing a second biopsy. 4 cases had at the onset classical signs of complement-mediated thrombotic microangiopathy (atypical hemolytic uremic syndrome) in combination with C3-GP or its subsequent development.Ultrastructural examination was performed in 40 cases. 8 patients (20%) were diagnosed dense deposit disease, 32 patients - C3-glomerulonephritis. Primary C3-GP was detected in 87 % of patients, secondary - in 13 % (monoclonal gammopathies - 10 %, autoimmune diseases - 3 %).Increased level of antibodies to factor H was detected in 2 of 12 patients who underwent this study. Nucleotide variants of unknown clinical significance in complement genes were detected in 2 out of 6 patients during molecular genetic testing.CONCLUSION. C3-GP is a severe variant of glomerular damage with a heterogeneous etiological structure, which requires the use of ultrastructural and molecular diagnostics, as well as clinical analysis and identification of pathogenetic mechanisms to determine approaches to therapy.

Excretion Patterns of Urinary Sediment and Supernatant Podocyte Biomarkers in Patients with Chronic Kidney Disease

Background: Podocyte depletion causes glomerulosclerosis, and persistent podocyte loss drives progression to end-stage kidney disease. Urinary sediment podocyte (u-sed Pod) mRNA excretion and urinary supernatant podocyte (u-sup PCX) protein have been used to monitor disease activity in glomerular diseases. However, the differences in these markers among pathologies have not been investigated. We examined the roles of these markers in kidney diseases. Methods: From January 2013 to March 2016, early morning urine samples were collected from 12 healthy controls and 172 patients with kidney disease (minor glomerular abnormality with mild proteinuria and/or microscopic hematuria, n = 15; minimal change nephrotic syndrome [MCNS], n = 15; membranous nephropathy [MN], n = 15; IgA nephropathy [IgAN], n = 60; crescentic glomerulonephritis [Cres GN], n = 19; lupus nephritis [LN], n = 10; others, n = 38). We examined u-sed Pod mRNA excretion, u-sup PCX protein and the urinary protein:creatinine ratio (u-PCR). Results: U-sed Pod mRNA excretion was significantly correlated with u-sup PCX protein (r = 0.37, p < 0.001). Both u-sed Pod mRNA excretion and u-sup PCX protein were significantly correlated with u-PCR (r = 0.53, p < 0.001 and r = 0.35, p < 0.001, respectively). Interestingly, u-sed Pod mRNA excretion was significantly increased in proliferative-type glomerulonephritis-including IgAN with extracapillary proliferative lesions, Cres GN and LN class IV-and significantly correlated with the rate of crescent formation, whereas u-sup PCX protein was significantly increased only in MN and subepithelial dense deposit-type LN compared with controls. Conclusions: Higher u-sed Pod mRNA excretion and u-sup PCX protein were associated with proliferative-type glomerulonephritis indicating podocyte detachment and subepithelial dense deposit-type glomerulonephritis, respectively. The results suggest that u-sed Pod mRNA excretion and u-sup PCX protein have usefulness for the diagnosis and measurement of disease activity with regard to glomerular diseases.

Mycoplasma pneumoniae Infection Associated C3 Glomerulopathy Presenting as Severe Crescentic Glomerulonephritis

C3 glomerulopathy (C3GP) is a group of diseases caused by a deregulated complement system, which encompasses both dense deposit disease and C3 glomerulonephritis. Renal manifestations of C3GP are primarily of proliferative glomerulonephritis, and only a few case reports of crescentic glomerulonephritis (CGN) in association with C3GP are available. Here is a case of an adult South-Asian female, who was diagnosed as seropositive acute Mycoplasma pneumoniae infection, with associated systemic manifestations, including immune-type extravascular haemolysis and nephrotic range proteinuria. Subsequent renal biopsy revealed CGN with disrupted Bowman’s capsules and necrotizing lesions. Immunofluorescence showed coarse granular mesangial C3 deposits with negative IgM, IgG, IgA, and C1q. The immunomorphological phenotype raised two possibilities including C3GP and infection-related glomerulonephritis (IRGN). Persistent proteinuria with no evidence of resolution even after 6 months of follow-up favoured C3GP over IRGN. The patient proceeded to end-stage renal failure requiring renal replacement despite aggressive immunosuppression. This case illustrates the rare association of CGN with C3GP induced by Mycoplasma pneumoniae infection, highlighting the importance of correct diagnosis as well as timely identification of triggering factors in CGN on patient outcome.