Amyloid fibril structure from the vascular variant of systemic AA amyloidosis.

Systemic AA amyloidosis is a debilitating protein misfolding disease in humans and animals. In humans, it occurs in two variants that are called 'vascular' and 'glomerular', depending on the main amyloid deposition site in the kidneys. Using cryo electron microscopy, we here show the amyloid fibril structure underlying the vascular disease variant.

Organ manifestations of COVID-19: what have we learned so far (not only) from autopsies?

The use of autopsies in medicine has been declining. The COVID-19 pandemic has documented and rejuvenated the importance of autopsies as a tool of modern medicine. In this review, we discuss the various autopsy techniques, the applicability of modern analytical methods to understand the pathophysiology of COVID-19, the major pathological organ findings, limitations or current studies, and open questions.

Deceased Donor Kidney Transplantation in the Eurotransplant Senior Program (ESP): A Single-Center Experience from 2008 to 2013.

Background: The aim of this study was to evaluate the outcome after transplantation of deceased allografts in donor/recipient pairs aged ≥65 years enrolled in the Eurotransplant Senior Program (ESP).

Material And Methods: In this retrospective cohort study we evaluated data from 89 patients transplanted under the ESP protocol from 2008 to 2013. Outcome parameters included graft and patient survival, rate of biopsy-proven acute rejections (BPAR), peri- and post-operative complications, tumor development, development of donor-specific antibodies (DSA), and the prognostic role of preimplantation biopsies.

Janus kinase 3 regulates renal 25-hydroxyvitamin D 1α-hydroxylase expression, calcitriol formation, and phosphate metabolism.

Calcitriol, a powerful regulator of phosphate metabolism and immune response, is generated by 25-hydroxyvitamin D 1α-hydroxylase in the kidney and macrophages. Renal 1α-hydroxylase expression is suppressed by Klotho and FGF23, the expression of which is stimulated by calcitriol. Interferon γ (INFγ) regulates 1α-hydroxylase expression in macrophages through transcription factor interferon regulatory factor-1.

Donor acute kidney injury and short-term graft outcome in renal transplantation.

Background: With increased waiting times for kidney transplantation, marginal organs from expanded criteria donors (ECD) are increasingly offered for allocation. In addition to ECD status, donors may have suffered from acute kidney injury (AKI) prior to organ procurement.

Methods: In this retrospective cohort study, we studied short-term allograft function in 517 kidney transplants performed between the years 2008-2014.

Mutations in WDR19 encoding the intraflagellar transport component IFT144 cause a broad spectrum of ciliopathies.

Background: An emerging number of clinically and genetically heterogeneous diseases now collectively termed ciliopathies have been connected to the dysfunction of primary cilia. We describe an 8-year-old girl with a complex phenotype that did not clearly match any familiar syndrome.

Case-diagnosis/treatment: Hypotonia, facial dysmorphism and retardation were noted shortly after birth.

BK viremia and polyomavirus nephropathy in 352 kidney transplants; risk factors and potential role of mTOR inhibition.

Background: Polyomavirus BK nephropathy (PyVAN) remains an important cause of early graft dysfunction and graft loss in kidney transplantation.

Methods: In this retrospective, single centre cohort study we studied the incidence and outcome of BK viral infection in 352 patients transplanted in 2008-2011.

Results: During follow-up viral replication was detected in 48 patients (13.

Oncofertility: combination of ovarian stimulation with subsequent ovarian tissue extraction on the day of oocyte retrieval.

Background: New anticancer treatments have increased survival rates for cancer patients, but often at the cost of sterility. Several strategies are currently available for preserving fertility. However, the chances of achieving a pregnancy with one technique are still limited.

Platelets are not critical effector cells for the time course of murine passive crescentic glomerulonephritis.

Although platelets are well-known effector cells of inflammatory renal disease, clinical studies were not able to establish platelet inhibition as an effective therapy. Our previous studies using Vasodilator stimulated Phosphoprotein- and P2Y1-deficient mice suggested some early, but no long-term effects of platelets in passive crescentic glomerulonephritis. To define the role of platelets for this disease model, passive crescentic glomerulonephritis was induced in 72 C57Bl/6 mice by intraperitoneal injection of sheep anti-rabbit glomerular basement membrane antibody on 2 consecutive days.

From red to white urine: a patient's nightmare with a rather benign outcome.

Background: Chyluria is a medical condition with presence of chyle in the urine. The disease is most prevalent in endemic regions of Africa and the Indian subcontinent where it is mostly caused by parasitic infections, particularly lymphatic filariasis due to wucheria bancrofti. Non-parasitic chyluria, however, is a very rare finding.

Lack of intestinal epithelial atg7 affects paneth cell granule formation but does not compromise immune homeostasis in the gut.

Genetic polymorphisms of autophagy-related genes have been associated with an increased risk to develop inflammatory bowel disease (IBD). Autophagy is an elementary process participating in several cellular events such as cellular clearance and nonapoptotic programmed cell death. Furthermore, autophagy may be involved in intestinal immune homeostasis due to its participation in the digestion of intracellular pathogens and in antigen presentation.

Four subunits (αβγδ) of the epithelial sodium channel (ENaC) are expressed in the human eye in various locations.

Purpose: The epithelial sodium channel (ENaC) is typically expressed in sodium-absorbing epithelia. Several reports suggest that ENaC is also expressed in ocular tissues and may play a role in aqueous humor secretion and glaucoma. However, the precise localization of ENaC in the human eye is still unclear.

The protective effect of prolyl-hydroxylase inhibition against renal ischaemia requires application prior to ischaemia but is superior to EPO treatment.

Background: Inhibition of the HIF regulating prolyl hydroxylation domain (PHDs) proteins prior to renal injury (preconditioning) has been shown to protect the kidney via activation of hypoxia-inducible transcription factors (HIF). Application of erythropoietin (EPO), one of the HIF target genes, has also been shown to be nephroprotective, and it remains unclear to what extent the effect of HIF induction is mediated by EPO. It is also unknown whether HIF activation after the onset of ischaemia (postconditioning) is still able to protect the kidney.

Role of guanylate binding protein-1 in vascular defects associated with chronic inflammatory diseases.

Rheumatic autoimmune disorders are characterized by a sustained pro-inflammatory microenvironment associated with impaired function of endothelial progenitor cells (EPC) and concomitant vascular defects. Guanylate binding protein-1 (GBP-1) is a marker and intracellular regulator of the inhibition of proliferation, migration and invasion of endothelial cells induced by several pro-inflammatory cytokines. In addition, GBP-1 is actively secreted by endothelial cells.

Severe metabolic alkalosis and recurrent acute on chronic kidney injury in a patient with Crohn's disease.

Background: Diarrhea is common in patients with Crohn's disease and may be accompanied by acid base disorders, most commonly metabolic acidosis due to intestinal loss of bicarbonate.

Case Presentation: Here, we present a case of severe metabolic alkalosis in a young patient suffering from M. Crohn.

Autocrine VEGF-VEGF-R loop on podocytes during glomerulonephritis in humans.

Background: Vascular endothelial growth factor (VEGF) is the most important and tightly regulated angiogenic cytokine in the kidney. Its activity is critical for capillary/glomerular preservation and repair, and recent studies have also demonstrated its relevance for the preservation of podocytes.

Methods: The present study investigated a large number (n = 153) of renal biopsies from patients with glomerulonephritis (GN) and evaluated the expression and activity of the glomerular VEGF system [VEGF, VEGF-R1, VEGF-R2 and biologically active VEGF as identified by VEGF-VEGF receptor complexes (VEGF-VEGF-R)] in parallel with markers of renal function, injury and repair.

An unusual case of hyponatraemia.

The differential diagnosis of hyponatraemia is manifold and includes hormonal disorders such as primary adrenal insufficiency or hypothyroidism. The diagnosis of adrenal insufficiency is always suggestive in cases of hypotension associated with hyponatraemia, hyperkalaemia and metabolic acidosis. We herein report a case of severe hyponatraemia in a patient with Addison's disease.

Influence of cyclooxygenase inhibitors on the function of the prostaglandin transporter organic anion-transporting polypeptide 2A1 expressed in human gastroduodenal mucosa.

The human organic anion-transporting polypeptide 2A1 (OATP2A1) is a prostaglandin transporter expressed in several tissues and plays an important role for local distribution of prostaglandins, which contribute to the integrity of gastric mucosa. Blockade of prostaglandin pathways by cyclooxygenase (COX) inhibitors has been associated with serious side effects such as gastrointestinal ulceration and bleeding. However, little is known regarding OATP2A1 expression in the upper gastrointestinal tract and the potential impact of cyclooxygenase inhibitors on OATP2A1 function.

Hydroxyethylstarch impairs renal function and induces interstitial proliferation, macrophage infiltration and tubular damage in an isolated renal perfusion model.

Introduction: The aim of the study was to evaluate some of the underlying pathomechanisms of hydroxyethylstarch (HES) induced adverse effects on renal function using 24 porcine kidneys in an isolated perfusion model over six hours.

Methods: Infusion of either 10% HES 200/0.5, 6% HES 130/0.

Angiostatic immune reaction in colorectal carcinoma: Impact on survival and perspectives for antiangiogenic therapy.

Angiogenesis and inflammation are the 2 major stroma reactions in colorectal carcinoma (CRC). Guanylate binding protein-1 (GBP-1) is a key mediator of angiostatic effects of inflammation. Therefore, we hypothesized that GBP-1 may be a biomarker of intrinsic angiostasis associated with an improved outcome in CRC patients.

Correlation of enhanced thrombospondin-1 expression, TGF-beta signalling and proteinuria in human type-2 diabetic nephropathy.

Background: Activation of the thrombospondin-1 (TSP-1)-TGF-beta pathway by glucose and the relevance of TSP-1-dependent activation of TGF-beta for renal matrix expansion, renal fibrosis and sclerosis have previously been demonstrated by our group in in vivo and in vitro studies. Design and methods. We investigated renal biopsies (n = 40) and clinical data (n = 30) of patients with diabetic nephropathy.

Acute syphilitic chorioretinitis after a missed primary diagnosis: a case report.

Introduction: Syphilis is well known as an infectious disease which can present with a large variety of symptoms. Clinical diagnosis can be difficult and may be complicated in modern medicine by immunosuppressive treatment and possible side effects of medication.

Case Presentation: We describe a rare case of placoid chorioretinitis due to Treponema pallidum which developed after the primary symptom of proteinuria was not recognized as a rare manifestation of syphilis.

A murine model of site-specific renal microvascular endothelial injury and thrombotic microangiopathy.

Despite the importance of endothelial injury and healing for primary and secondary renal disease and the availability of genetically engineered mouse models, to date no generally applicable murine disease model with site-specific renal endothelial injury has been established. We induced specific microvascular renal injury via selective renal arterial perfusion of the lectin concanavalin A (Con A) followed by sheep anti-concanavalin A and harvested tissues after 4 h, 24 h, days 3 and 7. Compared to control kidneys, histological evaluation demonstrated endothelial cell injury with subsequent complement, and platelet activation and thrombosis by light and electron microscopy.

P2Y1 gene deficiency protects from renal disease progression and capillary rarefaction during passive crescentic glomerulonephritis.

The metabotropic receptor P2Y1 is necessary for full ADP-induced platelet activation and is localized on various intrinsic renal cells, including mesangial cells, podocytes, and endothelial cells. To date, nothing is known about the role of the P2Y1 receptor during inflammatory renal disease. The role of the P2Y1 receptor was investigated using 22 P2Y1 gene-deficient (-/-) and 27 wild-type (wt) mice during the time course of passive crescentic nephrotoxic glomerulonephritis.