Association of ultrasonographic features with histologic findings in 71 dogs with protein-losing nephropathy (2008–2018)

OBJECTIVE To determine whether ultrasonographic features in dogs with protein-losing nephropathy (PLN) were associated with renal biopsy findings and compare corticomedullary ratios between dogs with PLN versus non-renal disease. ANIMALS 71 dogs with PLN and 33 dogs without renal disease. PROCEDURES Medical records and archived ultrasonographic images for dogs with PLN that underwent renal biopsy between 2008 and 2018 were reviewed. Corticomedullary ratios were measured. RESULTS In dogs with PLN, median serum creatinine and BUN concentrations and urine-protein-to-creatinine-ratio prior to renal biopsy were 3.4 mg/dL (interquartile range [IQR], 1.2 to 5.3 mg/dL), 80 mg/dL (IQR, 28 to 105 mg/dL), and 11.4 (IQR, 6.4 to 18.3), respectively. Histologic abnormalities within the tubulointerstitial space were associated with cortical echogenicity. Gastric wall thickness > 5 mm was associated with a histologic diagnosis of acute glomerular disease. Dogs with immune complex–mediated glomerular disease were more likely to have abnormal gastric mural architecture. Other ultrasonographic features of the kidneys, liver, and stomach and the presence of ascites did not help to differentiate immune complex–mediated from non-immune complex–mediated glomerular disease, acute from chronic disease, or amyloid from non-amyloid disease or distinguish whether tubulointerstitial disease was present or absent. Median left corticomedullary ratio for 66 dogs with PLN (1.2) was significantly higher than that for the 33 dogs without renal disease (1.0). Clinical Relevance Ultrasonographic features were poorly associated with specific pathological disorders in dogs with PLN. In this study, the corticomedullary ratio was higher in dogs with PLN, indicating the presence of cortical thickening, but the clinical relevance is unknown.

The parameters of gas discharge visualization (biophotonics) correlated with parameters of acupuncture points, EEG, HRV and hormones

Background. Previously we have been shown that exist strong canonical correlation between parameters of GDV and principal neuroendocrine factors of adaptation as well as parameters of leukocytogram, immunity and phagocytosis. This study, conducted on a much expanded contingent, will analyze the relationships between GDV parameters, on the one hand, and the parameters of acupuncture points (APs), EEG, HRV and adaptation hormones, on the other. Material and Methods. We observed twice 31 women and 29 men aged 26-76 years with dysfunction of neuroendocrine-immune complex. In the morning in basal conditions at first registered kirlianogram by the method of GDV by the device “GDV Chamber” (“Biotechprogress”, SPb, RF). Than we registered simultaneously EEG and HRV and recorded electrical conductivity of three pairs of Aps. Finally, a blood sample was taken to determine the plasma levels of the main hormones of adaptation: cortisol, testosterone and triiodothyronine. Results processed by method of canonical analysis, using the software package “Statistica 64”. Results. The coefficient of canonical correlation between the electrical conductivity of APs and gas-discharge image (GDI) parameters is 0,635; between APs and virtual Chakras parameters – 0,614; instead, between APs and GDV parameters as a whole – 0,707. The autonomic-endocrine constellation is somewhat more strongly associated with GDI parameters than with virtual Chakras parameters (0,769 vs 0,712). Additional inclusion of EEG parameters in the neuroendocrine set increases the strength of the canonical correlation to 0,869. Conclusion. The above data, taken together with the previous ones, state that between parameters of neuroendocrine-immune complex and GDV exist strong canonical correlation suggesting suitability of the latter method.

Rapidly progressive glomerulonephritis in children

Rapidly progressive glomerulonephritis (RPGN), characterized by a rapid development of nephritis with loss of kidney function in days or weeks, is typically associated histologically, with crescents in most glomeruli; and is a challenging problem, particularly in low resource settings. RPGN is a diagnostic and therapeutic emergency requiring prompt evaluation and treatment to prevent poor outcomes. Histopathologically, RPGN consists of four major categories, anti-glomerular basement membrane (GBM) disease, immune complex mediated, pauci-immune disorders and idiopathic /overlap disorders. Clinical manifestations include gross hematuria, proteinuria, oliguria, hypertension and edema. Diagnostic evaluation, including renal function tests, electrolytes, urinalysis/microscopy and serology including (anti GBM antibody, antineutrophil cytoplasmic antibody (ANCA)) starts simultaneously with management. An urgent renal biopsy is required to allow specific pathologic diagnosis as well as to assess disease activity and chronicity to guide specific treatment. The current guidelines for management of pediatric RPGN are adopted from adult experience and consist of induction and maintenance therapy. Aggressive combination immunosuppression has markedly improved outcomes, however, nephrotic syndrome, severe acute kidney injury requiring dialysis, presence of fibrous crescents and chronicity are predictors of poor renal survival. RPGN associated post infectious glomerulonephritis (PIGN) usually has good prognosis in children without immunosuppression whereas immune-complex-mediated GN and lupus nephritis (LN) are associated with poor prognosis with development of end stage kidney disease (ESKD) in more than 50% and 30% respectively. Given the need for prompt diagnosis and urgent treatment to avoid devastating outcomes, we conducted a review of the latest evidence in RPGN management to help formulate clinical practice guidance for children in our setting.Information sources and search strategy: The search strategy was performed in the digital databases of PubMed, Cochrane Library, google scholar, from their inception dates to December 2020. Three investigators independently performed a systematic search using the following search terms “Rapidly progressive glomerulonephritis” “children” “crescentic glomerulonephritis” “management” at the same time, backtracking search for references of related literature. doi: https://doi.org/10.12669/pjms.38.ICON-2022.5774 How to cite this:Moorani KN, Aziz M, Amanullah F. Rapidly progressive glomerulonephritis in children. Pak J Med Sci. 2022;38(2):417-425. doi: https://doi.org/10.12669/pjms.38.ICON-2022.5774 This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Extraglomerular immune complex deposition in lupus nephritis

Background Lupus nephritis (LN) is a common manifestation and a major cause of morbidity and mortality in systemic lupus erythematosus (SLE) patients. It is characterized by glomerular and often extraglomerular immune complex deposition. Purpose Given the emerging importance of the tubulointerstitial compartment, we conducted a retrospective study of 78 LN biopsies to enumerate the spectrum of extraglomerular immune complex deposition that can be observed in lupus nephritis by electron microscopy and to identify possible clinical or pathologic correlates. Results The presence of tubulointerstitial immune complex deposition often accompanied interstitial inflammation, but some discrepancies were also seen. Conclusions As target antigens are identified, correlation with glomerular, tubulointerstitial, and vascular immune complex deposition will be of increasing interest.

A case of immune-complex mediated glomerulonephritis associated with pembrolizumab

Introduction: Immune checkpoint inhibitors (ICI) are changing the way we treat cancer. However, these novel agents have various systemic adverse events that may preclude its use and cause poor patient outcomes. ICI-associated acute kidney injury is an emerging complication of this treatment. While tubulointerstitial disease is the most common pathologic finding of patients with ICI-associated AKI, there is sparse data in medical literature describing its association with glomerular disease. Case report: Here, we present a patient with metastatic lung adenocarcinoma who developed acute kidney injury and significant proteinuria after receiving pembrolizumab. The kidney biopsy revealed a membranoproliferative and diffuse segmental endocapillary proliferative pattern of glomerular injury. Management and outcome: Pembrolizumab was then held and high-dose prednisone was initiated, resulting in a rapid and dramatic improvement in kidney function and proteinuria. Discussion: We highlight a report of a patient diagnosed with immune-complex mediated glomerulonephritis associated with the use of pembrolizumab, who was successfully treated with drug withdrawal and corticosteroids.

Pseudomonas syringae effector HopZ3 suppresses the bacterial AvrPto1–tomato PTO immune complex via acetylation

The plant pathogen Pseudomonas syringae secretes multiple effectors that modulate plant defenses. Some effectors trigger defenses due to specific recognition by plant immune complexes, whereas others can suppress the resulting immune responses. The HopZ3 effector of P. syringae pv. syringae B728a (PsyB728a) is an acetyltransferase that modifies not only components of plant immune complexes, but also the Psy effectors that activate these complexes. In Arabidopsis, HopZ3 acetylates the host RPM1 complex and the Psy effectors AvrRpm1 and AvrB3. This study focuses on the role of HopZ3 during tomato infection. In Psy-resistant tomato, the main immune complex includes PRF and PTO, a RIPK-family kinase that recognizes the AvrPto effector. HopZ3 acts as a virulence factor on tomato by suppressing AvrPto1Psy-triggered immunity. HopZ3 acetylates AvrPto1Psy and the host proteins PTO, SlRIPK and SlRIN4s. Biochemical reconstruction and site-directed mutagenesis experiments suggest that acetylation acts in multiple ways to suppress immune signaling in tomato. First, acetylation disrupts the critical AvrPto1Psy-PTO interaction needed to initiate the immune response. Unmodified residues at the binding interface of both proteins and at other residues needed for binding are acetylated. Second, acetylation occurs at residues important for AvrPto1Psy function but not for binding to PTO. Finally, acetylation reduces specific phosphorylations needed for promoting the immune-inducing activity of HopZ3’s targets such as AvrPto1Psy and PTO. In some cases, acetylation competes with phosphorylation. HopZ3-mediated acetylation suppresses the kinase activity of SlRIPK and the phosphorylation of its SlRIN4 substrate previously implicated in PTO-signaling. Thus, HopZ3 disrupts the functions of multiple immune components and the effectors that trigger them, leading to increased susceptibility to infection. Finally, mass spectrometry used to map specific acetylated residues confirmed HopZ3’s unusual capacity to modify histidine in addition to serine, threonine and lysine residues.