Effects of phospholipase A2 receptor and thrombospondin type-1 domain-containing 7A expression in glomerular basement membranes on treatment response and renal outcome in membranous nephropathy.

BACKGROUND: The aim of this study was to define the clinicopathologic features of phospholipase A2 receptor (PLA2R) and/or thrombospondin type-1 domain-containing 7A (THSD7A) associated membranous nephropathy(MN) focusing on their impact to disease relapse and response to treatment. METHODS: A total of 201 patients were enrolled for baseline clinical and histopathological features and 102 patients with a clinical follow-up for more than 1 year were evaluated for outcomes. Immunohistochemical staining was performed with PLA2R and THSD7A antibodies on kidney biopsies and glomerular staining was evaluated. RESULTS: PLA2R expression was observed in 75% of the patients' biopsies; however, THSD7A expression was present only in 7 patients' biopsies (3.5%). No significant difference was found between histopathological and clinical features of PLA2R positive and negative patients, collectively. Glomerular PLA2R expression was significantly associated with complete and complete/partial remission with first-line treatment; however, overall complete, and complete/partial remission rates did not differ from PLA2R negative patients (p = 0.2 and p = 0.8). Male gender, the presence of IgG4 staining and a necessity of immunosuppressive treatment were significantly associated with glomerular PLA2R expression. One patient, who developed end-stage renal disease, had glomerular expression for both PLA2R and THSD7A. Three patients with THSD7A-positive MN achieved complete remission. CONCLUSIONS: The probability of achieving complete remission is high in patients with PLA2R-positive MN for whom the relapse rate was also higher. The overall renal outcome did not differ from PLA2R negative cases. Low incidence of THSD7A-positive MN reduces the possibility of future randomized controlled trials.

Renal Biopsy Prognostic Findings in Children With Atypical Hemolytic Uremic Syndrome.

BACKGROUND: The aim of this study was to investigate the histopathological findings in kidney biopsies in children with atypical hemolytic uremic syndrome (aHUS) and to determine whether specific pathological findings in aHUS have a prognostic value. METHODS: Renal biopsy specimens of 29 patients who were recorded in the national Turkish aHUS registry database were available for review. Histopathological findings were compared with the clinical and laboratory features at the presentation and the final outcome. RESULTS: The mean age at presentation and follow-up period was 4.9 ± 3.9 and 3.9 ± 3.0 years, respectively. The median time interval from the first symptom to biopsy was 10 days. Vascular thrombosis and interstitial fibrosis were significantly related to chronic kidney disease (CKD) requiring dialysis or kidney transplantation during follow-up (5.6-fold, for both). Glomerular necrosis, cortical necrosis, and glomerular sclerosis were markedly associated with CKD without dialysis (6.2-fold, 13.3-fold, and 8.8-fold, respectively). However, presence of endothelial swelling, subendothelial widening, and fragmented erythrocytes was found to be correlated with a favorable final outcome. CONCLUSIONS: Presence of vascular thrombosis, cortical necrosis, and glomerular sclerosis in histopathological evaluation correlated with developing CKD. Chronic changes in the interstitial compartment were also related to poor prognosis, a finding that has been shown for the first time in pediatric aHUS cases.

Changing trends in pediatric renal biopsies: analysis of pediatric renal biopsies in national nephrology registry data.

Renal biopsy is the gold standard method for determining the diagnosis, treatment, and prognosis in children with renal disease. This study aims to evaluate the histopathological features of pediatric renal biopsies obtained from the national nephrology registry in the last two decades. Data recorded in the Turkish Society of Nephrology Registry System (TSNRS) in 1991 as well as in between 2001 and 2010 were analyzed. A total of 3892 biopsies were recorded; with the least number in 1991 (total 103 biopsies from 17 centers) and the highest number in 2008 (total 654 biopsies from 23 centers). Glomerular diseases constituted the main group in the registry (62.64%), followed by systemic diseases (20.06%). Focal and segmental glomerulosclerosis (FSGS) and Henoch-Schönlein purpura (HSP) nephritis (IgA vasculitis) were the most common glomerular and systemic diseases, respectively. Overall prevalence of renal amyloidosis and membranous nephropathy (MN) was quite low (1.87% and 1.56%, respectively) in all periods. Compared to 1991, there was an increasing trend in the frequencies of certain disorders including hemolytic uremic syndrome (HUS), IgA nephropathy, and HSP nephritis; and there was a decrease in acute proliferative glomerulonephritis (GN) in 2008. As well as demonstrating the etiologies of renal diseases which can only be identified by renal biopsies, this study provides important information regarding the changing patterns of histopathological findings due to better management of pediatric renal diseases over the years in Turkey.

Unusual Presentation of an Adenocarcinoma of the Lung Metastasizing to the Mandible, Including Molecular Analysis and a Review of the Literature.

Lung cancer is the most frequent cause of cancer-related death worldwide. Metastases of non-small cell lung carcinoma to the oral and maxillofacial region are rare. Thus, the diagnosis of a metastatic lesion in the oral cavity is challenging to the clinician and to the pathologist. This report presents a case of a 72-year-old man with metastatic lung adenocarcinoma located in the posterior mandibular region. Next-generation sequencing analysis showed no important mutations in the relevant genes except in the TP53 tumor suppressor gene.

Clinicopathological Significance of the Proliferation Markers Ki67, RacGAP1, and Topoisomerase 2 Alpha in Breast Cancer.

Objectives The aims of this study are to evaluate expressions of Ki67, RacGAP1 (MgcRacGAP) and topoisomerase 2 alpha (TOP2a), the markers related with cell proliferation that have been proposed to affect the prognosis in the literature and correlate the results with clinicopathological parameters of breast cancer patients. Methods Ki67, RacGAP1, and TOP2a antibodies were applied immunohistochemically to the tissue micrarray blocks of 457 female breast cancer patients. The results were correlated with clinical, prognostic, histopathological features, and other immunohistochemical findings (estrogen receptor [ER], progesterone receptor [PR], HER2, cytokeratin [CK]5/6, CK14, epidermal growth factor receptor [EGFR] and vimentin), statistically. Results Ki67 expression demonstrated direct correlation with TOP2a expression, mitotic count, tumor grade, geographic necrosis, basal-like phenotype. RacGAP1 expression was directly correlated with TOP2a expression, nipple invasion, and number of metastatic lymph nodes, and it was inversely correlated with PR expression. TOP2a expression was directly correlated with vimentin and Ki67 expressions, mitotic count, tumor grade, and geographic necrosis, and nipple invasion, and negatively correlated with ER and PR expressions. Higher TOP2a and Ki67 expressions were correlated with shorter overall survival. Higher TOP2a expression and RacGAP1 positivity were directly correlated with shorter disease-free survival. Conclusion This study showed that the overexpressions of Ki67, RacGAP1, and TOP2a affect the prognosis adversely, thus to develop target therapies against RacGAP1 and TOP2a as well as using Ki67 as a part of routine pathology practice might be beneficial in breast cancer therapy and prediction of prognosis.

Preventive treatment of calcium oxalate crystal deposition with immortal flowers.

ETHNOPHARMACOLOGICAL RELEVANCE: A number of medicinal plants are used for their diuretic, urolithiatic and anti-inflammatory effects on urinary system problems in Turkey and the most common traditional remedy for kidney stones is the tea of immortal flowers. The aim of this study is to evaluate the preventive effect of infusions prepared from capitulums of Helichrysum graveolens (M.Bieb.) Sweet (HG) and Helichrysum stoechas ssp. barellieri (Ten.) Nyman (HS) on formation of kidney stones. MATERIALS AND METHOD: Sodium oxalate (Ox-70mg/kg intraperitoneally) was used to induce kidney stones on Wistar albino rats. At the same time, two different doses of the plant extracts (HG: 62.5 and 125mg/kg; HS: 78 and 156mg/kg) were dissolved in the drinking water and administered to animals for 5 days. Potassium citrate was used as positive control in the experiments. During the experiment, water intake, urine volume and body weights of the animals were recorded. At the end of the experiments, liver, kidney and body weights of the animals were determined; biochemical analysis were conducted on urine, blood and plasma samples. Histopathological changes in kidney tissues were examined and statistical analysis were evaluated. RESULTS: HS extract showed the highest preventive effect at 156mg/kg dose (stone formation score: 1.16), whereas a number of kidney stones were maximum in sodium oxalate group (stone formation score: 2.66). Helichrysum extracts decreased urine oxalate and uric acid levels and increased citrate levels significantly. In addition, Helichrysum extracts regulated the negative changes in biochemical and hematological parameters occurred after Ox injection. CONCLUSIONS: We conclude that Helichrysum extracts could reduce the formation and growth of kidney stones in Ox-induced urolithiasis and can be beneficial for patients with recurrent stones. In addition, this is the first study on the preventive effect of immortal flowers.

Protective effect of adrenomedullin on contrast induced nephropathy in rats / Efecto protector de la adrenomedulina en la nefropatía inducida por contraste en ratas

Background and aims: Contrast-induced nephropathy (CIN) has a growing incidence in which renal vasoconstriction and medullary hypoxia are important mechanisms. Therapeutic approaches are very restricted and there is a considerable interest in advancing preventive strategies. Adrenomedullin is a relatively novel peptide having antioxidant, vasoactive and vasodilatory properties. We aimed to investigate whether adrenomedullin might have a preventive role against the development of experimental CIN. Methods: Wistar albino rats (n=24) were allocated randomly into four equal groups of 6 each; Control (C), Adrenomedullin (A), Contrast Media (CM) and Adrenomedullin plus Contrast Media (ACM). All rats were deprived of water from day 1 to day 4 during 72 hours. Then, intravenous administrations of chemicals were performed. Adrenomedullin was given at dose of 12µg/kg to groups A and ACM. A single dose of high-osmolar contrast media; diatrizoate (Urografin 76%, Schering AG, Germany) was injected to groups CM and ACM at dose of 10mL/kg. On day 1 and 6 blood samples were drawn for renal function tests and inflammatory markers including TNF-α IL-1β, IL-6 and IL-18. After sacrification, kidney histologies were examined with hematoxylin-eosin staining. Results: Compared to CM group, serum cystatin-C levels on 6th day were found significantly lower in ACM group (p<0.05). Additionally, daily protein excretion rates, absolute changes in daily urine output and creatinine clearance values were significantly lower in ACM group than those in CM group (p<0.05). In histopathological evaluation, regarding the degree of tubular damage and medullary congestion scores, ACM group had slightly better scores compared to CM group; however the differences did not reach significance as shown in inflammatory markers. Conclusion: This study demonstrated a beneficial impact of adrenomedullin on deteriorated renal function tests in an experimental CIN model. Adrenomedullin might be a candidate agent for prophylaxis of CIN. However, further studies are needed to shed more light on this issue

Antecedentes y objetivos: La incidencia de la nefropatía inducida por contraste (NIC) está aumentando y la vasoconstricción renal y la hipoxia medular son mecanismos importantes. Los enfoques terapéuticos son muy limitados y existe un gran interés en avanzar en las estrategias preventivas. La adrenomedulina es un péptido relativamente nuevo con propiedades antioxidantes, vasoactivas y vasodilatadoras. Nuestro objetivo es investigar si la adrenomedulina puede jugar un papel preventivo frente al desarrollo de la NIC experimental. Métodos: Se distribuyeron ratas Wistar albinas (n = 24) de forma aleatoria en cuatro grupos de 6: control (C), adrenomedulina (A), medio de contraste (MC) y adrenomedulina más medio de contraste (AMC). Las ratas no ingirieron agua desde el día 1 al día 4 (durante 72 horas). Posteriormente, se les administraron las sustancias de forma intravenosa. Los grupos A y AMC recibieron una dosis de adrenomedulina de 12 µg/kg. Los grupos MC y AMC recibieron una única dosis de medio de contraste de alta osmolaridad: 10 ml/kg de diatrizoato (Urografin 76 %, Schering AG, Alemania). Los días 1 y 6 se tomaron muestras de sangre para realizar análisis de función renal y de marcadores inflamatorios, incluidos el TNF-α, IL-1β, IL-6 e IL-18. Tras el sacrificio, se examinaron las histologías renales con tinción hematoxilina-eosina. Resultados: En comparación con el grupo MC, los niveles de cistatina C sérica fueron significativamente inferiores en el grupo AMC (P < 0,05). Además, la tasa de excreción diaria de proteínas, los cambios absolutos en el gasto urinario diario y los valores de aclaramiento de la creatinina fueron significativamente inferiores en el grupo AMC que en el grupo MC (P < 0,05). En la evaluación histopatológica, en lo que respecta al grado de daño tubular y los valores de congestión medular, el grupo AMC presentaba niveles ligeramente mejores en comparación con el grupo MC. Sin embargo, según los marcadores inflamatorios, las diferencias no presentaron significación estadística. Conclusión: El estudio ha demostrado que la adrenomedulina resulta beneficiosa en los análisis de función renal deteriorada en un modelo experimental de NIC. Por lo tanto, la adrenomedulina puede ser un candidato para la profilaxis de la NIC. No obstante, se necesitan más estudios que arrojen luz sobre este tema

Protective effect of adrenomedullin on contrast induced nephropathy in rats.

BACKGROUND AND AIMS: Contrast-induced nephropathy (CIN) has a growing incidence in which renal vasoconstriction and medullary hypoxia are important mechanisms. Therapeutic approaches are very restricted and there is a considerable interest in advancing preventive strategies. Adrenomedullin is a relatively novel peptide having antioxidant, vasoactive and vasodilatory properties. We aimed to investigate whether adrenomedullin might have a preventive role against the development of experimental CIN. METHODS: Wistar albino rats (n=24) were allocated randomly into four equal groups of 6 each; Control (C), Adrenomedullin (A), Contrast Media (CM) and Adrenomedullin plus Contrast Media (ACM). All rats were deprived of water from day 1 to day 4 during 72 hours. Then, intravenous administrations of chemicals were performed. Adrenomedullin was given at dose of 12µg/kg to groups A and ACM. A single dose of high-osmolar contrast media; diatrizoate (Urografin 76%, Schering AG, Germany) was injected to groups CM and ACM at dose of 10mL/kg. On day 1 and 6 blood samples were drawn for renal function tests and inflammatory markers including TNF-α IL-1β, IL-6 and IL-18. After sacrification, kidney histologies were examined with hematoxylin-eosin staining. RESULTS: Compared to CM group, serum cystatin-C levels on 6th day were found significantly lower in ACM group (p<0.05). Additionally, daily protein excretion rates, absolute changes in daily urine output and creatinine clearance values were significantly lower in ACM group than those in CM group (p<0.05). In histopathological evaluation, regarding the degree of tubular damage and medullary congestion scores, ACM group had slightly better scores compared to CM group; however the differences did not reach significance as shown in inflammatory markers. CONCLUSION: This study demonstrated a beneficial impact of adrenomedullin on deteriorated renal function tests in an experimental CIN model. Adrenomedullin might be a candidate agent for prophylaxis of CIN. However, further studies are needed to shed more light on this issue.

Diverse phenotypic expression of NPHP4 mutations in four siblings.

Nephronophthisis (NPHP) is an autosomal recessive disease characterized by renal tubular basement membrane disruption, interstitial fibrosis and tubular cysts that progresses to end-stage kidney disease (ESKD). There are also characteristic extrarenal manifestations. Mutations of more than thirteen genes that can cause NPHP have been identified. We herein report four siblings from a consanguineous family, who carried the same NPHP4 mutations but presented with different disease phenotypes ranging from enuresis nocturna to ESKD. Diluted urine and echogenic kidneys in ultrasound examination were consistent, which is typical for 100% of the NPHP cases that have been described. Chronic kidney disease developed in the older two brothers. The observed phenotypic differences are likely to be related to environmental and epigenetic factors, oligogenic inheritance and modifier genes affecting the age of presentation of signs and symptoms. NPHP should be considered as an important cause of CKD in children, which insidiously progresses to ESKD, with no specific therapy available.

Micropapillary pattern in urothelial carcinoma: a clinicopathological analysis.

OBJECTIVES: Our aim was to review our pathological archive to find out the actual incidence of micropapillary pattern (MPP) in our urothelial carcinoma patient population and determine its correlation with clinical outcome. PATIENTS AND METHODS: 14 out of 170 cases with complete clinical follow-up were clinicopathologically analyzed. The extent of MPP was determined as tumor percentage. RESULTS: 12 further cases with MPP were defined in the review. The percentage of patients with positive MPP increased in parallel to the tumor stage. There was no considerable difference between MPP-positive and MPP-negative groups according to the progression rates in non-muscle-invasive and muscle-invasive groups. Progression-free survival was much shorter in MPP cases, but again without statistical significance. Also, there was no significant relation between percentage of MPP and progression-free survival. CONCLUSIONS: Awareness of pathologists about MPP and its highly possible relation with aggressive behavior must be raised, as it may be more common than reported. A multicentric review of a large number of cases with MPP is needed for a better definition of its biological behavior. Focal MPP cases may have a better prognosis but this needs to be confirmed.

Hamartoma of the larynx: an unusual cause of upper airway obstruction.

Hamartomas are rare lesions in the larynx. Both clinical and histopathological findings may be misleading to both the physician and the pathologist in terms of diagnosis. A 51-year-old female with the complaints of nonproductive cough and severe dyspnea lasting for a year was found to have a subglottic, submucosal mass almost totally obstructing the laryngeal lumen. Excisional biopsy was performed under suspensory direct laryngoscopy. Histopathological examination showed numerous, large, distended blood vessels, some of which had prominent thickened walls and mature adipose tissue beneath the surface epithelium. The final diagnosis was hamartoma, but we discussed its validity and other possible identifications in accordance with the literature.