Clinicopathological Relevance of PAX8 Expression Patterns in Acute Kidney Injury and Chronic Kidney Diseases.

Transcription factor PAX8, expressed during embryonic kidney development, has been previously detected in various kidney tumors. In order to investigate expression of PAX8 transcription factor in acute kidney injury (AKI) and chronic kidney diseases (CKD), immunohistochemical analysis was performed. Presence, location and extent of PAX8 expression were analyzed among 31 human kidney samples of AKI (25 autopsy cases, 5 kidney biopsies with unknown etiology and 1 AKI with confirmed myoglobin cast nephropathy), as well as in animals with induced postischemic AKI. Additionally, expression pattern was analyzed in 20 kidney biopsy samples of CKD. Our study demonstrates that various kidney diseases with chronic disease course that results in the formation of tubular atrophy and interstitial fibrosis, lead to PAX8 expression in the nuclei of proximal tubules. Furthermore, patients with PAX8 detected within the damaged proximal tubuli would be carefully monitored, since deterioration in kidney function was observed during follow-up. We also showed that myoglobin provoked acute kidney injury followed with large extent of renal damage, was associated with strong nuclear expression of PAX8 in proximal tubular cells. These results were supported and followed by data obtained in experimental model of induced postischemic acute kidney injury. Considering these findings, we can assume that PAX8 protein might be involved in regeneration process and recovery after acute kidney injury. Thus, accordingly, all investigation concerning PAX8 immunolabeling should be performed on biopsy samples of the living individuals.

Nonasthmatic Churg-Strauss syndrome superimposed on chronic pyelonephritis: a case report.

Churg-Strauss syndrome (CSS) is a granulomatous small-vessel vasculitis. Asthma is seen in the majority of patients with CSS, but atypical nonasthmatic forms of CSS are also being recognized. We herein describe a 67-year-old woman with a history of chronic pyelonephritis and drug allergy reactions who was admitted to our hospital because of worsening renal function preceded by fever, purpura, sinusitis, and a positive urine culture that confirmed a urinary infection. She was initially treated with pipemidic acid for 7 days, followed by clarithromycin for sinusitis. Laboratory tests on admission showed an absolute eosinophil count of 1750 cells/µL and serum creatinine concentration of 4.72 mg/dL. Urine and blood cultures showed no growth. Kidney biopsy revealed crescent formations with diffuse interstitial fibrosis and foci of eosinophil infiltration. An atypical form of CSS was diagnosed based on tissue eosinophilia, peripheral eosinophilia, and sinusitis. Intravenous methylprednisolone and cyclophosphamide pulse therapy together with hemodialysis treatment improved the patient's clinical condition but did not resolve the kidney damage. The onset of an atypical form of CSS in our patient manifested as symptoms and signs mimicking those of chronic pyelonephritis and drug allergy reactions. The patient's chronic kidney disease finally progressed to dialysis dependence.

PRMT1 expression in renal cell tumors- application in differential diagnosis and prognostic relevance.

BACKGROUND: Protein arginine methyltransferase-1 (PRMT1) is associated with the progression of various tumor types and the process of epithelial to mesenchymal transition (EMT). However, the expression of PRMT1 in renal cell tumors (RCT) is unknown. METHODS: We evaluated PRMT1 immunohistochemical (IHC) expression on tissue microarray (TMA) of 208 specimens of RCT, including clear cell renal cell carcinomas (ccRCC), papillary RCC type I and II (pRCC I and II), chromophobe RCC (chRCC), renal oncocytomas (RO), collecting duct carcinomas - Bellini (CDC) and multilocular cystic renal cell neoplasms of low malignant potential (MLCRN-LMP). Moreover, a subset of ccRCC, pRCC, chRCC, RO were also studied using conventional sections. PRMT1 expression in tumor tissue was compared to the IHC expression of EMT-related transcription factors (ZEB1, RUNX1, and TWIST1) and cell surface markers (ß-catenin, N- and E-cadherin). Additionally, qRT-PCR expression of PRMT1 in ccRCC, pRCC, and chRCC was evaluated and the results were compared to the mRNA PRMT1 transcript profiling data in The Cancer Genome Atlas (TCGA) and Genotype-Tissue Expression (GTEx) cohort. RESULTS: PRMT1 immunoreactivity was observed in the majority of ccRCC, RO, all MLCRN-LMP, but in a minority of chRCC (p = 0.044), and it was associated with low grade and low stage ccRCC (p = 0.014; p = 0.044, respectively). ZEB1 immunoreactivity was noted in all RO, in minority of chRCC and neither of MLCRN-LMP (p < 0.001). The majority of PRMT1-negative ccRCC was negative to ZEB1 and showed cytoplasmic expression of TWIST1 (p = 0.028; p < 0.001, respectively). PRMT1 positive ccRCC mostly expressed RUNX1 (p = 0.019). PRMT1 and ZEB1 expression were associated with better cancer-specific survival in patients with ccRCC (p = 0.029; p = 0.009, respectively). In multivariate analysis, ZEB1 expression was an independent prognostic factor for cancer-specific survival (hazard ratio [HR], 0.367; p = 0.026). Significant IHC heterogeneity was observed in PRMT1, ZEB1 and TWIST1 expression (p < 0.001). Homogenous loss of PRMT1 was associated with high grade and high stage ccRCC, while the homogenous loss of PRMT1 and ZEB1 was more frequent in patients who died of ccRCC (p = 0.017; p = 0.040; p = 0.044; p = 0.009, respectively). Relative mRNA-PRMT1 expression in both cohorts was down-regulated in tumor tissue compared to non-tumor parenchyma (p = 0.009). Unlike in our samples, mRNA-PRMT1 expression in the TCGA cohort was not correlated to ccRCC tumor stage or grade. PRMT1, ZEB1, and TWIST1 expression were not associated with EMT related aberrant ß-catenin expression, a gain of N-cadherin or loss of E-cadherin expression. Only RUNX1 was associated with a gain of N-cadherin (p = 0.003). CONCLUSIONS: IHC expression of PRMT1 may be characteristic for low grade and low stage ccRCC, while the homogenous loss of PRMT1 may be significant for high grade and high stage ccRCC. Both, PRMT1 and/or ZEB1 expression, could be associated with better survival of the patients with ccRCC.

Modulation of NCAM/FGFR1 signaling suppresses EMT program in human proximal tubular epithelial cells.

Neural cell adhesion molecule (NCAM) and fibroblast growth factor receptor 1 (FGFR1) cross-talk have been involved in epithelial-to-mesenchymal transition (EMT) process during carcinogenesis. Since EMT also contributes to maladaptive repair and parenchymal damage during renal fibrosis, we became encouraged to explore the role of NCAM/FGFR1 signaling as initiating or driving forces of EMT program in cultured human proximal tubular epithelial cells (TECs). TECs stimulated with TGF-ß1 (10ng/mL) was used as an established in vitro EMT model. TGF-ß1 downstream effectors were detected in vitro, as well as in 50 biopsies of different human kidney diseases to explore their in vivo correlation. NCAM/FGFR1 signaling and its modulation by FGFR1 inhibitor PD173074 (100nM) were analyzed by light microscopy, immunolabeling, qRT-PCR and scratch assays. Morphological changes associated with EMT appeared 48h after TGF-ß1 treatment and was clearly apparent after 72 hours, followed by loss of CDH1 (encoding E-Cadherin) and transcriptional induction of SNAI1 (SNAIL), SNAI2 (SLUG), TWIST1, MMP2, MMP9, CDH2 (N-Cadherin), ITGA5 (integrin-α5), ITGB1 (integrin-ß1), ACTA2 (α-SMA) and S100A4 (FSP1). Moreover, at the early stage of EMT program (24 hours upon TGF-ß1 exposure), transcriptional induction of several NCAM isoforms along with FGFR1 was observed, implicating a mechanistic link between NCAM/FGFR1 signaling and induction of EMT. These assumptions were further supported by the inhibition of the EMT program after specific blocking of FGFR1 signaling by PD173074. Finally, there was evidence for an in vivo TGF-ß1 pathway activation in diseased human kidneys and correlation with impaired renal excretory functions. Collectively, NCAM/FGFR1 signaling appears to be involved in the initial phase of TGF-ß1 initiated EMT which can be effectively suppressed by application of FGFR inhibitor.

Effects of Single and Combined Losartan and Tempol Treatments on Oxidative Stress, Kidney Structure and Function in Spontaneously Hypertensive Rats with Early Course of Proteinuric Nephropathy.

Oxidative stress has been widely implicated in both hypertension and chronic kidney disease (CKD). Hypertension is a major risk factor for CKD progression. In the present study we have investigated the effects of chronic single tempol (membrane-permeable radical scavenger) or losartan (angiotensin II type 1 receptor blocker) treatment, and their combination on systemic oxidative status (plasma thiobarbituric acid-reactive substances (pTBARS) production, plasma antioxidant capacity (2,2'-azino-bis(3-ethylbenzothiazoline-6-sulphonic acid, pABTS), erythrocyte antioxidant enzymes activities) and kidney oxidative stress (kTBARS, kABTS, kidney antioxidant enzymes activities), kidney function and structure in spontaneously hypertensive rats (SHR) with the early course of adriamycin-induced nephropathy. Adult SHR were divided into five groups. The control group received vehicle, while the other groups received adriamycin (2 mg/kg, i.v.) twice in a 21-day interval, followed by vehicle, losartan (L,10 mg/kg/day), tempol (T,100 mg/kg/day) or combined T+L treatment (by gavage) during a six-week period. Adriamycin significantly increased proteinuria, plasma lipid peroxidation, kidney protein oxidation, nitrite excretion, matrix metalloproteinase-1 (MMP-1) protein expression and nestin immunostaining in the kidney. Also, it decreased kidney antioxidant defense, kidney NADPH oxidase 4 (kNox4) protein expression and abolished anti-inflammatory response due to significant reduction of kidney NADPH oxidase 2 (kNox2) protein expression in SHR. All treatments reduced protein-to-creatinine ratio (marker of proteinuria), pTBARS production, kidney protein carbonylation, nitrite excretion, increased antioxidant capacity and restored kidney nestin expression similar to control. Both single treatments significantly improved systemic and kidney antioxidant defense, bioavailability of renal nitric oxide, reduced kMMP-1 protein expression and renal injury, thus retarded CKD progression. Losartan improved blood pressure, as well as tubular injury and restored anti-inflammatory defense by reverting kNox2 expression to the control level. Interestingly, tempol was more successful in reducing systemic oxidative stress, proteinuria, kMMP-1 and glomerulosclerosis. However, combined treatment failed to overcome the beneficial effects of single treatments in slowing down the progression of ADR-induced nephropathy in SHR.

Granulomatous interstitial nephritis associated with influenza A: H1N1 infection--A case report.

INTRODUCTION: The causes of acute tubulointerstitial nephritis can be grouped into four broad categories: medications, infections, immunologic diseases, or idiopathic processes. Here we report a 17-year-old female who developed acute kidney injury (AKI) due to granulomatous interstitial nephritis (GIN) associated with influenza A: H1N1 infection. CASE OUTLINE: The illness presented after two weeks of respiratory tract infection, skin rash and hypermenorrhea. On admission the patient was febrile, with bilateral pedal edema, macular skin rash, and auscultatory finding that suggested pneumonia. Laboratory investigations showed normocytic anemia, azotemia, hematuria and proteinuria. Renal ultrasound was normal. Antinuclear antibodies, antineutrophil cytoplasmic antibodies, lupus anticoagulant, antiphospholipid antibodies were negative with normal complement. Urine cultures including analysis for Mycobacterium tuberculosis were negative. The diagnosis of influenza A: H1N1 infection was made by positive serology. A kidney biopsy showed interstitial nephritis with peritubular granulomas. Glomeruli were normal. Staining for immunoglobulins A, M, G, and F was negative. The girl was treated with oseltamivir phosphate (Tamiflu; Genentech, Inc., South San Francisco, CA, USA) for five days, as well as with tapered prednisone after a starting dose of 2 mg/kg. The treatment resulted in a complete remission during two years of follow-up. CONCLUSION: We present a severe but reversible case of GIN and AKI associated with influenza A: H1N1 infection. Although a causal effect cannot be confirmed, this case suggests that influenza A: H1N1 should be considered in the differential diagnosis of GIN manifested with AKI in children.

Early post-transplant lymphoproliferative disorder ­ Case of fatal lymphoma after kidney transplantation.

Introduction: Post-transplant lymphoproliferative disorder (PTLD) is a common malignancy following organ transplantation. Risk for PTLD is associated with the use of anti-thymocyte globulin in the prevention and treatment of acute rejection following kidney transplantation. Case Outline: We report a case of fatal PTLD presented with sudden onset of fever. A 33-year-old male patient with primary diagnosis of left kidney agenesia underwent kidney transplantation six years following hemodialysis treatment initiation. Deceased donor was a 66-year-old female whose cause of death was cerebrovascular accident. Immunosuppressive regimen consisted of basiliximab, corticosteroids, tacrolimus, and mycophenolate mofetil. Six months upon transplantation the patient was hospitalized due to fever of unknown origin. All microbiological samples were negative, but abdominal ultrasound revealed round solid mass in the right native kidney. Right nephrectomy was performed showing tumor 35 × 35 × 20 mm in size within the 70 × 40 × 35 mm kidney. Pathohistological analysis confirmed very rare monomorphic B-cell PTLD ­ B-cell lymphoma, unclassifiable, with features intermediate between diffuse large B-cell lymphoma and classical Hodgkin lymphoma. Conclusion: We consider this case of PTLD following kidney transplantation particular because of the tumor mass in native kidney after basiliximab induction and rare pathohistology. In a transplanted patient with fever, PTLD must always be considered, irrespective of immunosuppressive regimen.

Variable Expression of Neural Cell Adhesion Molecule Isoforms in Renal Tissue: Possible Role in Incipient Renal Fibrosis.

Rare neural cell adhesion molecule (NCAM) positive cells have been previously described within the normal human adult kidney interstitium, speculating that they could increase in the interstitium with incipient interstitial renal fibrosis (IRF). In the present study, among 93 biopsy samples of various kidney diseases, NCAM+ interstitial cells were detected in 62.4% cases. An increased number of NCAM+ cells was significantly observed only in incipient IRF compared to normal renal tissues and advanced IRF stages (p<0.001), independently of underlying diseases (p = 0.657). All three major NCAM isoforms' RT-PCR bands were visible either in normal or in kidneys with incipient IRF, albeit their mRNA expression levels measured by qRT-PCR were different. Applying qRT-PCR on pure NCAM+ cells population, obtained by laser capture microdissection, significant mRNA over-expression of NCAM140kD isoform was found in NCAM+ cells within incipient IRF (p = 0.004), while NCAM120kD and NCAM180kD isoforms were not changed significantly (p = 0.750; p = 0.704; respectively). Simultaneously, qRT-PCR also showed significant αSMA (p = 0.014) and SLUG (p = 0.004) mRNAs up-regulation within the NCAM+ cells of incipient IRF, as well as highly decreased matrix metalloproteinases (MMP) -2 and -9 mRNAs (p = 0.028; p = 0.036; respectively). However, using double immunofluorescence MMP-9 could still be detectable on the protein level in rare NCAM+ cells within the incipient IRF. Further characterization of NCAM+ cells by double immunofluorescent labeling revealed their association with molecules involved in fibrosis. Fibroblast growth factor receptor 1 (FGFR1) and α5ß1 integrin were extensively expressed on NCAM+ cells within the incipient IRF areas, whereas human epididymis protein-4 (HE4) was found to be present in few NCAM+ cells of both normal and interstitium with incipient fibrosis. Heterogeneity of NCAM+ interstitial cells in normal and incipient IRF, concerning molecules related to fibrosis and variable expression of NCAM isoforms, could suggest diverse role of NCAM+ cells in homeostasis and in regulation of renal fibrosis in diseased kidneys.

Glomerular nestin expression: possible predictor of outcome of focal segmental glomerulosclerosis in children.

BACKGROUND: A high prevalence of chronic kidney disease among children with focal segmental glomerulosclerosis (FSGS) leads to a permanent quest for good predictors of kidney dysfunction. Thus, we carried out a retrospective cohort study in order to examine known clinical and morphological predictors of adverse outcome, as well as to investigate glomerular nestin expression as a potential new early predictor of kidney dysfunction in children with FSGS. Relationships between nestin expression and clinical and morphological findings were also investigated. METHODS: Among 649 renal biopsy samples, obtained from two children's hospitals, FSGS was diagnosed in 60 children. Thirty-eight patients, who met the criteria for this study, were followed up for 9.0 ± 5.2 years. Using Kaplan-Meier and Cox's regression analysis, potential clinical and morphological predictors were applied in two models of prediction: after disease onset and after the biopsy. RESULTS: The present study revealed the following significant predictors of kidney dysfunction: patients' ages at disease onset, as well as age at biopsy, resistance to corticosteroid treatment, serum creatinine level, urine protein/creatinine ratio, vascular involvement, tubular atrophy, interstitial fibrosis, and decreased glomerular nestin expression. CONCLUSIONS: The most important finding of our study is that nestin can be used as a potential new early morphological predictor of kidney dysfunction in childhood onset of FSGS, since nestin has been obviously decreased in both sclerotic and normal glomeruli seen by light microscopy.

NCAM and FGFR1 coexpression and colocalization in renal tumors.

Neural cell adhesion molecule (NCAM) and fibroblast growth factor receptor (FGFR) have a role in epithelial-mesenchymal transformation during tumor genesis. Interplay between both molecules activates FGFR signaling and it could be responsible for tumor development. Renal epithelial tumors were analyzed for FGFR1 and NCAM coexpression by immunohistochemistry and for colocalization of these molecules on the particular tumor cells by triple immunofluorescence. Detection of NCAM isoforms in renal tumors was evaluated by RT-PCR. Applying immunohistochemistry we revealed that the majority of analyzed renal neoplasms, including renal cell carcinoma (RCC) and oncocytoma coexpressed NCAM and FGFR1. Triple immunofluorescent technique confirmed that both markers are commonly colocalized on the same tumor cells. Interestingly, it seemed that different position of NCAM and FGFR1 expression on renal tumor cells is related to renal tumor type or grade: exclusively membranous FGFR1/NCAM expression occurred in low grade clear cell RCC (cRCC); cytoplasmatic and membranous expression was present in high grade cRCC and other RCC types; oncocytoma showed only cytoplasmatic staining of both markers. NCAM-140 and NCAM-120 were detected in almost all analyzed renal neoplasms. Expression of both molecules on different cell compartments in various kidney tumors indicated that NCAM/FGFR1 interaction could play distinct roles in renal tumor genesis.

Pulmonary renal syndrome in a child with coexistence of anti-neutrophil cytoplasmic antibodies and anti-glomerular basement membrane disease: case report and literature review.

BACKGROUND: Pulmonary renal syndrome (PRS), denoting the presence of diffuse alveolar hemorrhage and glomerulonephritis as manifestations of systemic autoimmune disease, is very rare in childhood. The coexistence of circulating anti-neutrophil cytoplasmic antibody (ANCA) and anti-glomerular basement membrane (GBM) disease in children affected by this syndrome is exceptional, with unfavorable outcome in five out of seven patients reported to date. We describe a child with PRS associated with both circulating anti-myeloperoxidase (anti-MPO) ANCA and anti-GBM disease on renal biopsy who was successfully treated with immunosuppressive therapy. CASE PRESENTATION: A 10-year old girl presented with fever, fatigue, malaise, and pallor followed by hemoptysis and severe anemia. Diffuse alveolar hemorrhage was revealed on fiberoptic bronchoscopy. Renal findings consisted of microscopic hematuria, moderate proteinuria, and anti-GBM disease on renal biopsy. ANCA with anti-MPO specificity were present whereas anti-GBM antibodies were on borderline for positivity. Methyl-prednisolone pulses followed by prednisone led to cessation of hemoptysis, marked improvement of lung fuction, and normal finding on chest x-ray within 10 days. An immunosuppressive regimen was then given consisting of prednisone daily for 4 weeks with subsequent taper on alternate day, i.v. cyclophosphamide pulses monthly for 6 doses, followed by mycophenolate mofetil that resulted in normal lung function tests, hemoglobin concentration, and anti-MPO level within four subsequent weeks. During 10-months of follow-up she remained well, her blood pressure and renal function tests were normal, and proteinuria and hematuria gradually resolved. CONCLUSION: We report a child with an exceptionally rare coexistence of circulating ANCA and anti-GBM disease manifesting as PRS in whom renal disease was not the prominent part of clinical presentation, contrary to other reported pediatric patients. A review of literature on disease with double positive antibodies is also presented. Evaluation of a patient with PRS should include testing for presence of different antibodies. An early diagnosis and rapid institution of aggressive immunosuppressive therapy can induce remission and preserve renal function. Renal prognosis depends on the extent of kidney injury at diagnosis and appropriate treatment.

Rapidly progressive course of primary renal synovial sarcoma--case report.

INTRODUCTION: Primary kidney sarcoma, especially synovial sarcoma (SS), is a very rare neoplasm. Preoperative signs and symptoms are very similar to renal cell carcinoma, therefore, the proper diagnosis is very difficult and usually made after nephrectomy.This is a case report of primary renal SS. CASE OUTLINE: A 38-year-old man presented with a history of fever and hematuria, and right flank pain 3 weeks ago. Abdominal computerized tomography revealed a heterogeneous well-marginated soft tissue mass arising in the lower part of the right kidney. Right nephrectomy was performed. A cystic tumor of 120 x 85 mm in size with soft solid growth, and with the extensive areas of hemorrhage and necrosis was seen on gross examination. Histopathology revealed a neoplasm composed of solid monomorphic sheets of spindle cells. Immunohistochemistry showed tumor cells strongly positive for BCL2, CD99, CD56 and vimentin, and focally positive for epithelial membrane antigen (EMA). The histological diagnosis of primary renal SS was based on morphology and immunohistochemistry. FISH analysis and RT-PCR was carried out on formalin-fixed paraffin-embedded tissue sections. The molecular analysis demonstrated translocation of SYT gene on chromosome 18 and SSX2 gene on chromosome X. The findings were consistent with diagnosis of SS. CONCLUSION: Our case shows that histopathological diagnosis of primary kidney SS, although difficult, is possible to be made on the basis of morphological and immunohistochemical analysis. However, this diagnosis should be corroborated by molecular techniques confirming SYT-SSX translocation on chromosome 18 and chromosome X. Here we present visceral monophasic SS with aggressive clinical course and poor outcome.

Expression of neural cell adhesion molecule in renal cell carcinoma.

Neural cell adhesion molecule (NCAM) is important for cell migration and it could be expressed in some renal cell carcinoma (RCC). In recent decades, the incidence of RCC has been steadily rising by 2-4% each year. In this study NCAM expression and correlation with nuclear grade in different RCC were analyzed. We analyzed NCAM expression on 7 different RCC cell lines and 32 different RCC by immunohistochemistry, immunofluorescence, Western blot and FACS analysis. NCAM expression is detected in 6 cell lines and 16 RCC cases. NCAM-140 kDa isoform is expressed in different RCC and RCC cell lines. NCAM expression in non-invasive clear cell RCC is lower than in clear cell RCC with high nuclear grade. Expression of NCAM is not exclusive for specific RCC type, so NCAM can not be used as a specific diagnostic marker for RCC. NCAM expression is in correlation with nuclear grade in clear cell RCC, suggesting that NCAM expression is involved in aggressive behavior and metastatic potential in RCC.

Indications and results of renal biopsy in children: a 10-year review from a single center in Serbia.

BACKGROUND: This study was conducted to retrospectively investigate the indications for renal biopsy in native kidneys and to analyze pathological findings in the last 10 years in a single tertiary pediatric hospital in Serbia. METHODS: All patients who underwent renal biopsy at our hospital between 2001 and 2010 were included in the present study. Renal biopsy was performed under fluoroscopy with a biopsy gun. All renal biopsies were studied under light and immunofluorescent microscopy, while electron microscopy was rarely performed. RESULTS: The study group included 150 patients (56% female) who underwent 158 percutaneous native kidney biopsies. Median age was 11.5 years (range 0.2-20 years). The most frequent indications for renal biopsy were nephrotic syndrome (32.9%), asymptomatic hematuria (23.4%), urinary abnormalities in systemic diseases (15.8%) and proteinuria (11.4%). Primary glomerulonephritis (GN) was the most common finding (57.4%), followed by secondary GN (15.5%) and tubulointerstitial diseases (4.5%). According to histopathological diagnosis, the most common causes of primary GN were focal segmental glomerulosclerosis (20.9%), mesangioproliferative GN (14.6%), IgA nephropathy (8.9%) and minimal change disease (13%). Lupus nephritis (6%) and Henoch-Schönlein nephritis (4%) were the most common secondary glomerular diseases. CONCLUSIONS: The epidemiology of glomerular disease in our single-center report is similar to that in data from adjacent Croatia and Greece. Focal segmental glomerulosclerosis was the dominant histopathological finding, followed by mesangioproliferative GN and IgA nephropathy.

Morphology of Balkan endemic nephropathy: current state.

Balkan endemic nephropathy (BEN) is interesting renal disease, because of its unique clinical, epidemiological and morphological characteristics: intensive interstitial fibrosis and tubular atrophy without any inflammation. In the present paper we evaluate the incidence of BEN from the morphological point of view for the last decade. Therefore we analyzed material obtained from autopsies, kidney biopsies and nephrectomy due to upper urothelial cancer (UUC) from the patients which were divided into two groups: those with permanent residence in BEN areas and those from nonendemic areas. At the Institute of Pathology, University of Belgrade for the last 15 years we had only 1 autopsy due to BEN out of 6,825. More than 30 years ago there were over 50 autopsy cases of BEN at the same institute. For the last decade we had only 2 kidney biopsies suspected for BEN out of 2,182, but morphologically not confirmed as BEN. However, previously we had over 40 kidney biopsies diagnosed as early or late stage of BEN. At the Clinical Center of Serbia 180 nephrectomies were performed due to UUC. The incidence of UUC for the last five years in BEN regions has significantly decreased, whereas at the same time in non-BEN regions it has remained on the same level. There was no morphological difference of the renal tissue adjacent to tumor between patients from BEN and non-BEN regions. According to our study based on routine pathological work, we could clearly conclude that BEN today is more clinical and epidemiological than a morphological entity.

[A patient with systemic lupus erythematosus and lupus nephritis: a 12-year follow-up].

INTRODUCTION: Systemic lupus erythematosus (SLE) is a chronic immunological disease causing a significant morbidity and mortality in younger women and involving several organs and systems, most often the kidneys, being consequently the incidence of lupus nephritis (LN) about 60%. CASE REPORT: We reported a 57 year-old patient with the diagnosed SLE in 1995. Pathohistological analysis of kidney biopsy revealed LN type V. The patient was treated with corticosteroid pulses and azathioprine during one year. A remission was achieved and maintained with prednisone, 15 mg daily. Nephrotic relapse was diagnosed in 2006 and the second kidney biopsy revealed recent kidney infarction due to extensive vasculitis. Soon, a cerebrovascul insult developed and CT-scan revealed endocranial infarctus. The patient was treated with corticosteroids and cyclophosphamide pulses (totally VI monthly pulses), and also with low-molecular heparine, anticoagulants and salicylates because of the right leg phlebothrombosis. After the pulses, the patient was adviced to take prednisone 20 mg daily and azothioprine 100 mg daily, and 6 months later mycophenolate mofetil because of persistent active serological immunological findings (ANA 1:320) and nephrotic syndrome. Mycophenolate mofetil was efficient in inducing and maintaining remission of nephrotic syndrome. CONCLUSION: The aim of LN treatment is to achieve and maintain remission, improve patients' outcome, reduce the toxicity of immunosuppressive drugs and the incidence of relapses.Mycophenolate mofetil was shown to be efficient in inducing and maintaining remission of nephrotic syndrome in the frame of LN.

The effects of potassium channel opener P1075 on the human saphenous vein and human internal mammary artery.

Because adrenergic contractions can contribute to the development of life-threatening spasm of coronary artery bypass graft, this study was performed to investigate the effect of adenosine 3-phosphate (ATP)-sensitive K channel (KATP) opener P1075 on contractions of isolated human saphenous vein (HSV) and human internal mammary artery (HIMA). Phasic contractions were evoked by electric field stimulation (20 Hz) and noradrenaline. The sustained contractions were evoked by phenylephrine. The presence of pore-forming Kir6.1 and Kir6.2 subunits of the KATP channels in the HIMA and only Kir6.2 in the HSV was confirmed immunomorphologically. P1075 inhibited in the HSV only, the electrical field stimulation contractions more strongly than noradrenaline contractions. In addition, the phenylephrine contractions of HSV were more sensitive to P1075 in comparison to those of HIMA. Glibenclamide, a KATP channel blocker antagonized the vasodilatation produced by P1075 in both grafts differently, because its effect was more prominent on the P1075-induced inhibition of contractions of HSV than of HIMA. We conclude that P1075 has a vasorelaxant effect and inhibited adrenergic contractions of the tested grafts. This effect is graft and vasoconstrictor selective and seems to be mediated by Kir6.1- and/or Kir6.2-containing KATP channels. Thus, P1075 can be considered as a potential drug in the prevention of graft spasm.

[Pax-2 antigen expression in kidney tumours].

UNLABELLED: Pax-2 transcriptional factor is expressed during kidney development and could re-express in renal tumors. The aim of this study was to examine Pax-2 expression in different types of renal cell carcinoma (RCC) in order to see whether it is good immunohistochemical marker. METHOD: We analyzed 48 different renal tumours stained with Pax-2 antibody. Pax-2 positive reaction was noticed in nucleus or cytoplasm. Expression of this antigen in tumours tissue was correlated with tumour stage and nuc-lear grade. Pax-2 expression between different histological RCC types was analyzed by chi2 test and Fishers test for two in-depended samples. RESULTS: Pax-2 is expressed by a high percentage of re-nal tumors regardless of histologic type. Significant diffe-rence of Pax-2 expression between oncocytomas and chromofobe RCC was found. CONCLUSION: Nuclear expression of Pax-2 is useful diagnostic kidney tumour marker. Pax-2 showed stronger expression in lower malignancy kidney tumours and in oncocytomas, than in high grade RCC like in those with sarcomatoid differentiation

[Autosomal recessive polycystic kidney disease: case report].

INTRODUCTION: Autosomal recessive polycystic kidney disease is the most common heritable cystic renal disease occurring in infancy and childhood. The clinical spectrum of signs and symptoms of this disease is widely variable ranging from perinatal death to a milder progressive form, which cannot be diagnosed until adolescence. CASE OUTLINE: A female neonate born in the 35th/36th week of gestation. The findings of all standard medical examinations of the neonate done by the mother were within normal limits. A few days before delivery physicians at a regional medical centre revealed enlarged kidneys and oligohydramnios. The delivery was performed by caesarean section. The vital functions of the newborn were in critical condition so that she was referred to the University Children's Hospital in Belgrade. Soon after admission, despite all undertaken measures, the infant died. Autopsy was done at the Institute of Pathology of the Belgrade Clinical Centre. All findings were typical for autosomal recessive polycystic kidney disease. The kidneys were hugely enlarged, with cystically dilated collecting ducts that almost completely replaced the renal parenchyma. The lungs were mildly hypoplastic. The liver showed dilated portal spaces, with multiple irregularly branching bile ducts. The cause of death was respiratory distress and renal failure. CONCLUSION: In all cases of congenital anomalies of the kidney with lethal ending it is necessary to perform autopsy and aimed genetic investigation.

Reduced progression of adriamycin nephropathy in spontaneously hypertensive rats treated by losartan.

BACKGROUND: The aim of the study was to investigate the antihypertensive effects of angiotensin II type-1 receptor blocker, losartan, and its potential in slowing down renal disease progression in spontaneously hypertensive rats (SHR) with adriamycin (ADR) nephropathy. METHODS: Six-month-old female SHR were randomly selected in six groups. Two control groups (SH(6), SH(12)) received vehicle. Groups ADR(6), ADR+LOS(6) and ADR(12), and ADR+LOS(12) received ADR (2 mg/kg/b.w. i.v.) twice in a 3-week interval. Group ADR+LOS(6) received losartan (10 mg/kg/b.w./day by gavages) for 6 weeks and group ADR+LOS(12) for 12 weeks after second injection of ADR. Animals were killed after 6 or 12 weeks, respectively. Haemodynamic measurements were performed on anaesthetized animals, blood and urine samples were taken for biochemical analysis and the left kidney was processed for morphological studies. RESULTS: Short-term losartan treatment, besides antihypertensive effect, improved glomerular filtration rate and ameliorated glomerulosclerosis resulting in decreased proteinuria. Prolonged treatment with losartan showed further reduction of glomerulosclerosis associated with reduced progression of tubular atrophy and interstitial fibrosis, thus preventing heavy proteinuria and chronic renal failure. Losartan reduced uraemia and increased urea clearance in advanced ADR nephropathy in SHR. Histological examination showed that losartan could prevent tubular atrophy, interstitial infiltration and fibrosis in ADR nephropathy. CONCLUSION: Losartan reduces the rate of progression of ADR-induced focal segmental glomerulosclerosis to end-stage renal disease in SHR.