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1.
Pathologe ; 42(Suppl 1): 76-80, 2021 Nov.
Article in English | MEDLINE | ID: mdl-33646362

ABSTRACT

Apart from pulmonary disease, acute kidney injury (AKI) is one of the most frequent and most severe organ complications in severe coronavirus disease 2019 (COVID-19). The SARS-CoV­2 virus has been detected in renal tissue. Patients with chronic kidney disease (CKD) before and on dialysis and specifically renal transplant patients represent a particularly vulnerable population. The increasing number of COVID-19 infected patients with renal involvement led to an evolving interest in the analysis of its pathophysiology, morphology and modes of virus detection in the kidney. Meanwhile, there are ample data from several autopsy and kidney biopsy studies that differ in the quantity of cases as well as in their quality. While the detection of SARS-CoV­2 RNA in the kidney leads to reproducible results, the use of electron microscopy for visualisation of the virus is difficult and currently critically discussed due to various artefacts. The exact contribution of indirect or direct effects on the kidney in COVID-19 are not yet known and are currently the focus of intensive research.


Subject(s)
Acute Kidney Injury , COVID-19 , Humans , Kidney , RNA, Viral , SARS-CoV-2
2.
Pathologe ; 42(2): 183-187, 2021 Mar.
Article in German | MEDLINE | ID: mdl-33527157

ABSTRACT

Apart from pulmonary disease, acute kidney injury (AKI) is one of the most frequent and most severe organ complications in severe coronavirus disease 2019 (COVID-19). The SARS-CoV­2 virus has been detected in renal tissue. Patients with chronic kidney disease (CKD) before and on dialysis and specifically renal transplant patients represent a particularly vulnerable population. The increasing number of COVID-19 infected patients with renal involvement led to an evolving interest in the analysis of its pathophysiology, morphology and modes of virus detection in the kidney. Meanwhile, there are ample data from several autopsy and kidney biopsy studies that differ in the quantity of cases as well as in their quality. While the detection of SARS-CoV­2 RNA in the kidney leads to reproducible results, the use of electron microscopy for visualisation of the virus is difficult and currently critically discussed due to various artefacts. The exact contribution of indirect or direct effects on the kidney in COVID-19 are not yet known and are currently the focus of intensive research.


Subject(s)
Acute Kidney Injury , COVID-19 , Humans , Kidney , RNA, Viral , SARS-CoV-2
3.
Pathologe ; 39(6): 576-582, 2018 Nov.
Article in German | MEDLINE | ID: mdl-30167781

ABSTRACT

Nephrotoxicity or renal side effects of drugs are frequent and may vary in their clinical presentation. Various types of acute and chronic kidney disease are known to develop as a consequence or side effect of a long list of drugs with nephrotoxicity most commonly being associated with injury in the tubulointerstitial compartment. In addition, drug-induced glomerular and vascular disease have also been reported, either as the result of direct cellular injury or immune-mediated injury to glomerular or endothelial cells. From a clinical point of view it is important to recognize such drug-induced nephropathies early in order to prevent or adequately treat them to favour kidney recovery and to avoid long-lasting negative consequences for kidney function.This article will focus on the typical morphology and pathogenesis of some frequent drug-induced renal diseases.


Subject(s)
Acute Kidney Injury , Drug-Related Side Effects and Adverse Reactions , Kidney Diseases , Endothelial Cells , Humans , Kidney
4.
Histol Histopathol ; 33(8): 871-886, 2018 Aug.
Article in English | MEDLINE | ID: mdl-29616745

ABSTRACT

AIMS: Mast cells (MC) and dendritic cells (DC) have immune modulatory function and can influence T-cell activity. Both cell types have been found in atherosclerotic plaques and are thought to play an important role for plaque stability. Compared to matched segments of the non-renal population, patients with chronic kidney disease (CKD) show a more pronounced and more aggressive course of atherosclerosis with higher plaque calcification and significantly higher complications rates. It was the aim of this study to analyze the number and localization of MCs and DCs, macrophages, T- and B-cells as well as the expression of markers of inflammation such as CRP and NFκB in calcified and non-calcified atherosclerotic plaques of patients with CKD and control patients. METHODS: Fifty coronary atherosclerotic plaques from patients with endstage CKD (CKD, n=25) and control (n=25) patients were categorized according to the Stary classification and investigated using immunohistochemistry (markers for MC, DC, T, B, macrophage and NFκB). Expression was analyzed separately for the complete plaque area as well as for the different plaque subregions and correlations were analyzed. RESULTS: We found only very few DCs and MCs per lesion area with slightly increased numbers in calcified plaques. MCs per plaque area were significantly more frequent in CKD than in control patients and this was independent of plaque calcification. MCs were most frequently found in the shoulder and basis of the plaque. DCs per plaque area were significantly less in calcified plaques of CKD compared to control patients. In control, but not in CKD patients, DCs were significantly more frequent in calcified than in non-calcified plaques. Within the plaques DCs were similarly distributed between all 4 subregions. CONCLUSIONS: Coronary atherosclerotic plaques of CKD patients showed a significantly higher number of MCs whereas DCs were less frequent compared to control patients particularly if plaques were calcified. These findings might indicate a potential proinflammatory role of MCs, but not of DCs in atherosclerotic lesions of CKD patients, adding another characteristic of advanced atherosclerosis in these patients.


Subject(s)
Coronary Artery Disease/pathology , Coronary Vessels/pathology , Dendritic Cells/pathology , Mast Cells/pathology , Plaque, Atherosclerotic , Renal Insufficiency, Chronic/complications , Aged , B-Lymphocytes/immunology , B-Lymphocytes/pathology , Case-Control Studies , Coronary Artery Disease/complications , Coronary Artery Disease/immunology , Coronary Vessels/immunology , Dendritic Cells/immunology , Female , Humans , Inflammation Mediators/analysis , Macrophages/immunology , Macrophages/pathology , Male , Mast Cells/immunology , Middle Aged , Renal Insufficiency, Chronic/diagnosis , Severity of Illness Index , T-Lymphocytes/immunology , T-Lymphocytes/pathology , Vascular Calcification/pathology
5.
Internist (Berl) ; 58(12): 1319-1323, 2017 Dec.
Article in German | MEDLINE | ID: mdl-28555379

ABSTRACT

We report on a 59-year-old woman who presented with nausea, fatigue, arterial hypertension, and acute renal failure. Clinical examination, laboratory findings of blood and urine and abdominal sonography were inconclusive. Renal biopsy revealed infiltration by a diffuse large B­cell lymphoma. In fluorodeoxyglucose positron emission tomography/computed tomography tracer enrichment was demonstrated in both kidneys, skeletal system and retroperitoneal lymph nodes. Renal function improved already after the first cycle of R­CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, prednisone). After chemotherapy, a complete remission, normalization of blood pressure and renal function were achieved.


Subject(s)
Acute Kidney Injury/etiology , Hypertension/etiology , Lymphoma, Large B-Cell, Diffuse/diagnosis , Antibodies, Monoclonal, Murine-Derived/therapeutic use , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Biopsy , Bone and Bones/pathology , Cyclophosphamide/therapeutic use , Diagnosis, Differential , Doxorubicin/therapeutic use , Fatigue/etiology , Female , Humans , Kidney/pathology , Lymph Nodes/pathology , Lymphoma, Large B-Cell, Diffuse/drug therapy , Middle Aged , Nausea/etiology , Positron Emission Tomography Computed Tomography , Prednisone/therapeutic use , Rituximab , Vincristine/therapeutic use
6.
Oncoimmunology ; 5(5): e1127494, 2016 May.
Article in English | MEDLINE | ID: mdl-27467940

ABSTRACT

Beyond their mere presence, the distribution pattern of inflammatory cells is of special interest. Our hypothesis was that random distribution may be a clear indicator of being non-functional as a consequence of lack of interaction. Here, we have assessed the implication of cell-to-cell distances among inflammatory cells in anal squamous cell carcinoma and a possible association with survival data. Thirty-eight patients suffering from anal carcinoma were studied using tissue microarrays, double staining immunohistochemistry, whole slide scanning and image analysis software. Therapy consisted of concurrent radiochemotherapy. Numbers of stromal and intraepithelial tumor-infiltrating inflammatory cells (TIC) and the distances between cells were quantified. Double-staining of FoxP3(+) cells with either CD8(+), CD1a(+) or CD20(+) cells was performed. Measured cell-to-cell distances were compared to computer simulated cell-to-cell distances leading to the assumption of non-randomly distributed and therefore functional immune cells. Intraepithelial CD1a(+) and CD20(+) cells were randomly distributed and therefore regarded as non-functional. In contrary, stromal CD20(+) cells had a non-random distribution pattern. A non-random distance between CD20(+) and FoxP3(+) cells was associated with a clearly unfavorable outcome. Measured distances between FoxP3(+) cells were distinctly shorter than expected and indicate a functional active state of the regulatory T cells (Treg). Analysis of cell-to-cell distances between TIC has the potential to distinguish between suppressed non-functional and functionally active inflammatory cells. We conclude that in this tumor model most of the CD1a(+) cells are non-functional as are the intraepithelial CD20(+) cells, while stromal CD20(+) cells and FoxP3(+) cells are functional cells.

7.
Br J Cancer ; 113(3): 510-9, 2015 Jul 28.
Article in English | MEDLINE | ID: mdl-26110975

ABSTRACT

BACKGROUND: The prognosis of solid malignancies has been shown to depend on immunological parameters, such as macrophage polarisation (M1/M2). Recently, it was reported that preoperative oral surgery leads to a worsening of oral squamous cell carcinomas (OSCC) prognosis. Diagnostic incision biopsies are oral surgery procedures that might lead to healing-associated M2 macrophage polarisation with a potential negative influence on tumour biology. No studies have compared macrophage polarisation in OSCC biopsies and tumour specimens. METHODS: Preoperative diagnostic incision biopsies (n=25) and tumour resection specimens (n=34) of T1/T2 OSCC were processed for immunohistochemistry to detect CD68-, CD11c-, CD163- and MRC1-positive cells. Samples were digitised using whole-slide imaging, and the expression of macrophage markers was quantitatively analysed. RESULTS: Carcinoma tissues obtained during OSCC tumour resections showed a significantly (P<0.05) increased CD163 cell count (M2 macrophages) compared with tissues obtained during preoperative incision biopsies. Additionally, the CD163/CD68 ratio (an indicator of M2 polarisation) was significantly (P<0.05) higher in tumour resection specimens than in biopsies. CONCLUSIONS: This study revealed for the first time an increase in M2 polarisation in samples obtained during OSCC tumour resection surgery compared with preoperative incision biopsies. The biopsy-induced tissue trauma might explain the observed shift in macrophage polarisation towards the tumour-promoting M2 type and could lead to accelerated tumour progression.


Subject(s)
Carcinoma, Squamous Cell/immunology , Cell Polarity , Macrophages/physiology , Mouth Neoplasms/immunology , Biopsy , Carcinoma, Squamous Cell/metabolism , Carcinoma, Squamous Cell/pathology , Carcinoma, Squamous Cell/surgery , Chemotaxis , Disease Progression , Female , Humans , Immunohistochemistry , Macrophages/metabolism , Male , Middle Aged , Mouth Neoplasms/metabolism , Mouth Neoplasms/pathology , Mouth Neoplasms/surgery , Time Factors
8.
Am J Physiol Renal Physiol ; 308(3): F198-208, 2015 Feb 01.
Article in English | MEDLINE | ID: mdl-25391897

ABSTRACT

Expression of proximal tubular organic anion transporters Oat1 and Oat3 is reduced by PGE2 after renal ischemia and reperfusion (I/R) injury. We hypothesized that impaired expression of Oat1/3 is decisively involved in the deterioration of renal function after I/R injury. Therefore, we administered probenecid, which blocks proximal tubular indomethacin uptake, to abolish the indomethacin-mediated restoration of Oat1/3 regulation and its effect on renal functional and morphological outcome. Ischemic acute kidney injury (iAKI) was induced in rats by bilateral clamping of renal arteries for 45 min with 24-h follow-up. Low-dose indomethacin (1 mg/kg) was given intraperitoneally (ip) at the end of ischemia. Probenecid (50 mg/kg) was administered ip 20 min later. Indomethacin restored the expression of Oat1/3, PAH net secretion, and PGE2 clearance. Additionally, indomethacin improved kidney function as measured by glomerular filtration rate (GFR), renal perfusion as determined by corrected PAH clearance, and morphology, whereas it reduced renal cortical apoptosis and nitric oxide production. Notably, indomethacin did not affect inflammation parameters in the kidneys (e.g., monocyte chemoattractant protein-1, ED1+ cells). On the other hand, probenecid blocked the indomethacin-induced restoration of Oat1/3 and moreover abrogated all beneficial effects. Our study indicates that the beneficial effect of low-dose indomethacin in iAKI is not due to its anti-inflammatory potency, but in contrast to its restoration of Oat1/3 expression and/or general renal function. Inhibition of proximal tubular indomethacin uptake abrogates the beneficial effect of indomethacin by resetting the PGE2-mediated Oat1/3 impairment, thus reestablishing renal damage. This provides evidence for a mechanistic effect of Oat1/3 in a new model of the induction of renal damage after iAKI.


Subject(s)
Acute Kidney Injury/metabolism , Ischemia/drug therapy , Organic Anion Transport Protein 1/metabolism , Organic Anion Transporters, Sodium-Independent/metabolism , Reperfusion Injury/drug therapy , Acute Kidney Injury/drug therapy , Acute Kidney Injury/physiopathology , Animals , Disease Models, Animal , Female , Glomerular Filtration Rate/drug effects , Indomethacin/administration & dosage , Indomethacin/pharmacology , Ischemia/metabolism , Kidney/metabolism , Rats, Sprague-Dawley , Reperfusion Injury/metabolism
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