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Janina Müller-Deile, Patricia Schröder, Lynne Beverly-Staggs, Rebecca Hiss, Jan Fiedler, Jenny Nyström, Thomas Thum, Hermann Haller, Mario Schiffer
So far the pathomechanism of preeclampsia in pregnancy is focussed on increased circulating levels of soluble fms-like tyrosin kinase-1 (sFLT-1) that neutralizes glomerular VEGF-A expression and prevents its signaling at the glomerular endothelium. As a result of changed glomerular VEGF-A levels endotheliosis and podocyte foot process effacement are typical morphological features of preeclampsia. Recently, microRNA-26a-5p (miR-26a-5p) was described to be also upregulated in the preeclamptic placenta. We found that miR-26a-5p targets VEGF-A expression by means of PIK3C2α in cultured human podocytes and that miR-26a-5p overexpression in zebrafish causes proteinuria, edema, glomerular endotheliosis and podocyte foot process effacement...
February 26, 2018: Scientific Reports
Karolina Panek-Laszczyńska, Andrzej Konieczny, Ewa Milewska, Krystyna Dąbrowska, Remigiusz Bąchor, Wojciech Witkiewicz, Zbigniew Szewczuk
CONTEXT: Preeclampsia (PE) is a pregnancy-related disease, and it is a leading cause of maternal and neonatal morbidity and mortality. It is characterized by the new onset of hypertension after 20 weeks of gestation together with signs of organ damage, most commonly the kidneys. The treatment of PE is symptomatic and final intervention requires delivery, regardless of the gestational age of the foetus. Furthermore, PE is a risk factor for developing cardiovascular disease and chronic kidney disease - even many years after the delivery...
November 27, 2017: Biomarkers: Biochemical Indicators of Exposure, Response, and Susceptibility to Chemicals
Hernán Trimarchi
Chronic kidney disease is a prevalent condition that affects millions of people worldwide and is a major risk factor of cardiovascular morbidity and mortality. The main diseases that lead to chronic kidney disease are frequent entities as diabetes mellitus, hypertension and glomerulopathies. One of the clinical markers of kidney disease progression is proteinuria. Moreover, the histological hallmark of kidney disease is sclerosis, located both in the glomerular and in the interstitial compartments. Glomerulosclerosis underscores an irreversible lesion that is clinically accompanied by proteinuria...
September 6, 2017: World Journal of Nephrology
Hernán Trimarchi, Romina Canzonieri, Amalia Schiel, Cristian Costales-Collaguazo, Aníbal Stern, Matías Paulero, Tatiana Rengel, José Andrews, Alejandro Iotti, Mariano Forrester, Fernando Lombi, Vanesa Pomeranz, Romina Iriarte, Alexis Muryan, Elsa Zotta
BACKGROUND: Podocyturia may determine the evolution to podocytopenia, glomerulosclerosis, and renal failure. According to the Oxford classification of IgA nephropathy (IgAN), the S1 lesion describes glomerulosclerosis. Urokinase-type plasminogen activator receptor (uPAR) participates in podocyte attachment, while CD80 increases in glomerulosclerosis. We measured uPAR-positive urinary podocytes and urinary CD80 (uCD80) in controls and in IgAN subjects with M1E0S0T0 and M1E0S1T0 Oxford scores to assess a potential association between podocyturia, inflammation, and glomerulosclerosis...
May 2017: Nephron Extra
Itsuko Furuta, Tianyue Zhai, Takeshi Umazume, Satoshi Ishikawa, Ami Hosokawa, Takashi Kojima, Kentaro Chiba, Takahiro Yamada, Mamoru Morikawa, Hisanori Minakami
AIM: Urine podocin mRNA expression and urine podocin : nephrin mRNA expression ratio (PNR) increase with increasing proteinuria during pregnancy complicated with pre-eclampsia (PE). This suggests that urine podocytes with reduced nephrin mRNA expression are abundant in pathological podocyturia. The aim of this study was therefore to determine post-partum changes in podocyturia and PNR in relation to proteinuria after pre-eclampsia (PE). METHODS: A total of 137 peripartum urine specimens, consisting of 72 and 65 from 24 and 30 women with PE and normotensive control pregnancies (NCP), respectively, were studied...
June 2017: Journal of Obstetrics and Gynaecology Research
Hernán Trimarchi, Romina Canzonieri, Amalia Schiel, Juan Politei, Cristian Costales-Collaguazo, Aníbal Stern, Matías Paulero, Tatiana Rengel, Lara Valiño-Rivas, Mariano Forrester, Fernando Lombi, Vanesa Pomeranz, Romina Iriarte, Alexis Muryan, Alberto Ortiz, María Dolores Sanchez-Niño, Elsa Zotta
Background. Despite enzyme replacement therapy, Fabry nephropathy still progresses. Podocyturia is an irreversible event that antedates proteinuria and leads to chronic renal failure. We evaluated a potential mechanism of podocyte detachment via the expression of the urokinase-type Plasminogen Activator Receptor (uPAR) in urinary podocytes of Fabry patients. Methods. This is a cross-sectional study that included controls (n = 20) and Fabry patients (n = 44) either untreated (n = 23) or treated with agalsidase-β (n = 21)...
2017: International Journal of Nephrology
H Trimarchi, M Paulero, R Canzonieri, A Schiel, A Iotti, C Costales-Collaguazo, A Stern, M Forrester, F Lombi, V Pomeranz, R Iriarte, T Rengel, I Gonzalez-Hoyos, A Muryan, E Zotta
IgA nephropathy is the most frequent cause of primary glomerulonephritis, portends erratic patterns of clinical presentation, and lacks specific treatment. In general, it slowly progresses to end-stage renal disease. The clinical course and the response to therapy are usually assessed with proteinuria and serum creatinine. Validated biomarkers have not been identified yet. In this report, we present a case of acute renal injury with proteinuria and microscopic hematuria in a young male. A kidney biopsy disclosed IgA nephropathy...
2017: Case Reports in Nephrology
Itsuko Furuta, Tianyue Zhai, Takeshi Umazume, Satoshi Ishikawa, Kinuko Nakagawa, Takashi Kojima, Takahiro Yamada, Mamoru Morikawa, Hisanori Minakami
Changes in hemodynamics and blood pressure occur shortly before and after childbirth regardless of the mode of delivery. This study aimed to test the hypothesis that parturition induces a temporal increase in podocyturia monitored by podocyte-specific protein podocin mRNA expression levels (Pod-mRNA). A total of 105 urine specimens, consisting of 43 and 62 from 18 and 20 otherwise healthy women with vaginal delivery (VD) and elective cesarean delivery (ECS), respectively, were studied. Determination of urine protein and creatinine (Cr) concentrations and quantitative analyses of Pod-mRNA, nephrin mRNA (Nep-mRNA), synaptopodin mRNA (Syn-mRNA), and aquaporin 2 mRNA expression were performed using RT-PCR in pelleted urine samples...
June 1, 2017: American Journal of Physiology. Renal Physiology
Itsuko Furuta, Tianyue Zhai, Takeshi Umazume, Satoshi Ishikawa, Kinuko Nakagawa, Rina Akaishi, Takahiro Yamada, Mamoru Morikawa, Hisanori Minakami
AIM: Hyperfiltration is a cause of podocyturia and occurs physiologically in the kidney of pregnant women. Podocyturia is increased in preeclamptic pregnancies, but it is unclear whether there is also any increase in uncomplicated pregnancies. This study was performed to examine whether podocyturia and urine aquaporin 2 mRNA expression are increased in healthy pregnant women (PW) compared to healthy non-pregnant women (NPW). METHODS: Eleven urines obtained from 11 NPW and longitudinal 76 urines from 40 PW with uncomplicated pregnancies (median number [range] of urine samples/person, 2 [1 - 3]) were studied...
February 11, 2017: Journal of Obstetrics and Gynaecology Research
Ligia Petrica, Mihaela Vlad, Adrian Vlad, Gheorghe Gluhovschi, Florica Gadalean, Victor Dumitrascu, Roxana Popescu, Cristina Gluhovschi, Petru Matusz, Silvia Velciov, Flaviu Bob, Sorin Ursoniu, Daliborca Vlad
AIMS: Detection of podocytes in the urine of patients with type 2 diabetes may indicate severe injury to the podocytes. In the course of type 2 diabetes the proximal tubule is involved in urinary albumin processing. We studied the significance of podocyturia in relation with proximal tubule dysfunction in type 2 diabetes. METHODS: A total of 86 patients with type 2 diabetes (34-normoalbuminuria; 30-microalbuminuria; 22-macroalbuminuria) and 28 healthy subjects were enrolled in the study and assessed concerning urinary podocytes, podocyte-associated molecules, and biomarkers of proximal tubule dysfunction...
September 2017: Journal of Diabetes and its Complications
Sooraj Baijnath, Saravanakumar Murugesan, Irene Mackraj, Prem Gathiram, Jagidesa Moodley
We investigated the effects of sildenafil citrate (SC) on podocyturia in N (ω)-nitro-L-arginine methyl ester hydrochloride (L-NAME) model of pre-eclampsia (PE). One hundred and twenty Sprague-Dawley rats (SDR) were divided into five groups like pregnant control (PC), early-onset PE (EOPE), late-onset PE(LOPE), early and late-onset PE with SC-treated groups [EOPE (SC); LOPE (SC)]. PE was induced in SDR by oral administration of L-NAME in drinking water for 4-8 days for EOPE and 8-14 day for LOPE. The blood pressure, urine volume and total urine protein were increased in EOPE and LOPE groups when compared to PC, and all the above parameters decreased in EOPE (SC) and LOPE (SC) groups when compared to EOPE and LOPE groups, respectively...
March 2017: Molecular and Cellular Biochemistry
Brent Fall, C Ronald Scott, Michael Mauer, Stuart Shankland, Jeffrey Pippin, Jonathan A Jefferson, Eric Wallace, David Warnock, Behzad Najafian
Chronic kidney disease is a major complication of Fabry disease. Podocytes accumulate globotriaosylceramide inclusions more than other kidney cell types in Fabry patients. Podocyte injury occurs early in age, and is progressive. Since injured podocytes detach into the urine (podocyturia), we hypothesized that podocyturia would increase in Fabry patients and correlate with clinical severity of Fabry nephropathy. Urine specimens from 39 Fabry patients and 24 healthy subjects were evaluated for podocyturia. Most of the Fabry patients and many healthy subjects had podocyturia...
2016: PloS One
Itsuko Furuta, Tianyue Zhai, Satoshi Ishikawa, Takeshi Umazume, Kinuko Nakagawa, Takahiro Yamada, Mamoru Morikawa, Hisanori Minakami
AIM: Podocyte depletion in the kidney is associated with end-stage kidney disease (ESKD). Pre-eclampsia (PE) increases the risk of ESKD in later life. This study was performed to determine whether nephrinuria (soluble nephrin in the urine) is correlated with proteinuria and/or podocyturia (podocytes in the urine) in PE women. METHODS: Eighty-three urine samples, consisting of 45 and 38 samples from 27 normotensive and nine PE women, respectively, underwent simultaneous determination of nephrin, protein, and creatinine concentrations in the urine supernatant and quantitative analysis of podocyte-specific protein mRNA expression...
January 2017: Journal of Obstetrics and Gynaecology Research
H Trimarchi, R Canzonieri, A Schiel, C Costales-Collaguazo, J Politei, A Stern, M Paulero, T Rengel, J Andrews, M Forrester, M Lombi, V Pomeranz, R Iriarte, A Muryan, E Zotta, M D Sanchez-Niño, A Ortiz
BACKGROUND: Certain glomerulopathies are associated with increased levels of CD80 (B7-1). We measured the urinary excretion of CD80, podocyturia and proteinuria in controls and in subjects with Fabry disease either untreated or on enzyme replacement therapy (ERT). METHODS: Cross-sectional study including 65 individuals: controls (n = 20) and Fabry patients (n = 45, 23 of them not on ERT and 22 on ERT). Variables included age, gender, urinary protein/creatinine ratio (UPCR), estimated glomerular filtration rate (eGFR), urinary uCD80/creatinine ratio (uCD80) and podocyturia...
October 13, 2016: Journal of Translational Medicine
Tianyue Zhai, Itsuko Furuta, Rina Akaishi, Satoshi Ishikawa, Mamoru Morikawa, Takahiro Yamada, Takahiro Koyama, Hisanori Minakami
Podocyte injury has been suggested to induce phenotypic alteration of glomerular podocytes and accelerate the detachment of podocytes from the glomeruli resulting in podocyturia. However, it is not clear whether podocyte phenotypic alteration occurs in the urine of women with preeclampsia (PE). Seventy-seven and 116 pelleted urine samples from 38 and 18 women at various stages of normal and PE pregnancies, respectively underwent quantitative analysis of podocyte-specific or associated protein mRNA expression, including podocin, nephrin, and synaptopodin using RT-PCR...
April 7, 2016: Scientific Reports
Ester Miranda Pereira, Adalberto Socorro da Silva, Anatália Labilloy, José Tiburcio do Monte Neto, Semiramis Jamil Hadad do Monte
INTRODUCTION: Fabry disease is a lysosomal storage disorder due to abnormalities in the GLA gene (Xq22). Such changes result in the reduction/absence of activity of the lysosome enzyme α-GAL, whose function is to metabolize globotriaosylceramide (Gb3). Renal disease is a major clinical outcome of the accumulation of Gb3. Podocyte injury is thought to be a major contributor to the progressive loss of the renal function and may be found altered even before the onset of microalbuminuria...
March 2016: Jornal Brasileiro de Nefrologia: ʹorgão Oficial de Sociedades Brasileira e Latino-Americana de Nefrologia
Hernán Trimarchi, Romina Canzonieri, Amalia Schiel, Juan Politei, Aníbal Stern, José Andrews, Matías Paulero, Tatiana Rengel, Alicia Aráoz, Mariano Forrester, Fernando Lombi, Vanesa Pomeranz, Romina Iriarte, Pablo Young, Alexis Muryan, Elsa Zotta
No abstract text is available yet for this article.
June 2016: Journal of Nephrology
H Trimarchi, R Canzonieri, A Muryan, A Schiel, A Araoz, M Paulero, J Andrews, T Rengel, M Forrester, F Lombi, V Pomeranz, R Iriarte, E Zotta
No specific or efficient treatment exists for Alport syndrome, an X-linked hereditary disease caused by mutations in collagen type IV, a crucial component of the glomerular basement membrane. Kidney failure is usually a major complication of the disease, and patients require renal replacement therapy early in life. Microhematuria and subsequently proteinuria are hallmarks of kidney involvement, which are due to primary basement membrane alterations that mainly cause endothelial thrombosis and podocyte contraction and ulterior irreversible detachment...
2016: Case Reports in Nephrology
Juliana B Mansur, Amélia R P Sabino, Sonia K Nishida, Gianna Mastroianni Kirsztajn
OBJECTIVE: To establish the occurrence and intensity of podocyturia and its relation to grade of disease activity, as defined by clinical and laboratory criteria. METHODS: Prospective, cross-sectional study involving 50 patients with lupus nephritis and 29 controls, which had podocyturia levels determined from random urine samples using an immunofluorescence technique. Disease activity was graded by BILAG (renal criteria) and an additional system used in the service (S2)...
2016: Renal Failure
Hernán Trimarchi, Romina Canzonieri, Amalia Schiel, Juan Politei, Aníbal Stern, José Andrews, Matías Paulero, Tatiana Rengel, Alicia Aráoz, Mariano Forrester, Fernando Lombi, Vanesa Pomeranz, Romina Iriarte, Pablo Young, Alexis Muryan, Elsa Zotta
BACKGROUND: Proteinuria suggests kidney involvement in Fabry disease. We assessed podocyturia, an early biomarker, in controls and patients with and without enzyme therapy, correlating podocyturia with proteinuria and renal function. METHODS: Cross-sectional study (n = 67): controls (Group 1, n = 30) vs. Fabry disease (Group 2, n = 37) subdivided into untreated (2A, n = 19) and treated (2B, n = 18). Variables evaluated: age, gender, creatinine, CKD-EPI, proteinuria, podocyte count/10 20× microscopy power fields, podocytes/100 ml urine, podocytes/g creatininuria (results expressed as median and range)...
December 2016: Journal of Nephrology
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