bluuebunny/crossref_metadata_2025_split huggingface dataset:
Transforming Growth Factor-β Is a Potent Inhibitor of Extracellular Matrix Degradation by Cultured Human Mesangial Cells
Authors: BARICOS WILLIAM H. , CORTEZ SHIRLEY L. , DEBOISBLANC MICHAEL , XIN SHI 
Published: April 2021

Abstract.
Accumulation of the glomerular extracellular matrix (ECM) is a pivotal event in the progression from acute glomerular injury to end-stage renal disease. Although enhanced ECM synthesis has been demonstrated to contribute to ECM accumulation, the role of decreased ECM degradation is largely unknown. It was previously shown that glomerular ECM degradation is mediated by a plasminogen activator (PA)/plasmin/matrix metalloproteinase 2 (MMP-2) cascade. However, little information is available regarding the factors that regulate the activity of this degradative cascade in normal or pathologic states. Transforming growth factor-β1 (TGF-β1) is shown here to be a potent inhibitor of ECM degradation by cultured human mesangial cells. Using human mesangial cells grown on thin films of 125I-labeled Matrigel, dose-dependent inhibition of ECM degradation in the presence of TGF-β1 was observed, reaching >90% inhibition with 0.4 ng/ml TGF-β1. Addition of anti-TGF-β antibodies (4 μg/ml) in the absence of exogenous TGF-β increased ECM degradation (1.8 ± 0.2-fold versus controls, P < 0.05). In contrast, platelet-derived growth factor, at concentrations up to 10 ng/ml, had no effect on ECM degradation. TGF-β completely blocked the conversion of plasminogen to plasmin and markedly reduced the conversion of latent MMP-2 to active MMP-2. TGF-β did not significantly alter the levels of tissue PA, total MMP-2, or tissue inhibitor of metalloproteinase-1, but did increase the levels of PA inhibitor-1 (1.8-fold, P < 0.05), the major physiologic inhibitor of PA. These data document that TGF-β is a potent inhibitor of ECM degradation by cultured human mesangial cells, and they suggest that decreased mesangial matrix degradation, caused by TGF-β-mediated decreases in the activity of the PA/plasmin/MMP-2 cascade, may contribute to the glomerular matrix accumulation that occurs in progressive renal disease.
Resistance to Remnant Nephropathy in the Wistar-Furth Rat
Authors: FITZGIBBON WAYNE R. , GREENE EDDIE L. , GREWAL JASJIT S. , HUTCHISON FLORENCE N. , SELF SALLY E. , LATTEN SAJATA Y. , ULLIAN MICHAEL E. 
Published: April 2021

Abstract.
The Wistar-Furth rat, an inbred strain resistant to actions of mineralocorticoids, was used to study the concept that mineralocorticoids contribute to progressive renal injury. It was postulated that if chronic nephropathy depends on aldosterone and if Wistar-Furth rats are resistant to aldosterone, remnant nephropathy would be attenuated in Wistar-Furth rats. Wistar-Furth rats and control Wistar rats were subjected to 5/6 nephrectomy or a sham procedure and then followed for 4 wk. Renal ablation resulted in hypertension at 4 wk in both strains (164 ± 5 [Wistar-Furth] versus 184 ± 7 [Wistar] mmHg mean arterial pressure), with sham animals remaining normotensive (134 ± 6 mmHg). Renal damage in response to 5/6 nephrectomy was greatly decreased in Wistar-Furth rats compared with Wistar rats. Albuminuria was markedly less in Wistar-Furth rats (12.7 ± 4.2 [Wistar-Furth] versus 97.4 ± 22.6 [Wistar] mg/d per 100 g body wt, P < 0.01). Glomerular damage, consisting of mesangial proliferation, mesangial lysis, and segmental necrosis, was observed in 42% of glomeruli from Wistar rats but in 0% of glomeruli from Wistar-Furth rats (P < 0.01). To address the possibility that higher BP in partially nephrectomized Wistar rats mediated the greater renal damage, the study was repeated, with Wistar rats (not Wistar-Furth rats) being treated with a hydralazine-reserpine-hydrochlorothiazide regimen. Although this antihypertensive regimen equalized BP (conscious systolic) (144 ± 8 mmHg [Wistar] versus 157 ± 7 mmHg [Wistar-Furth] at 4 wk), albuminuria remained more than 10-fold greater in Wistar rats. In summary, renal damage upon 5/6 nephrectomy was markedly reduced in Wistar-Furth rats, a finding not attributable to reduced systemic BP. Since Wistar-Furth rats have been shown previously to be resistant to the actions of mineralocorticoids, the data from the present study support the hypothesis that aldosterone mediates, at least in part, the renal injury attendant to renal mass reduction.
Evidence that Microdeletions in the α Globin Gene Protect Against the Development of Sickle Cell Glomerulopathy in Humans
Authors: GUASCH ANTONIO , ZAYAS CARLOS F. , ECKMAN JAMES R. , MURALIDHARAN KASINATHAN , ZHANG WEI , ELSAS LOUIS J. 
Published: April 2021

Abstract.
There is a large variability in the severity of the clinical manifestations of sickle cell anemia (SSA), including renal involvement. Haplotypes in the β-globin gene cluster associated with the geographical origin of the sickle mutation, as well as microdeletions in the α-globin genes, could provide an epigenetic influence on the heterogeneous outcome in SSA. It has been determined that the cause of progressive renal insufficiency in SSA is a glomerulopathy, clinically detected by the presence of macroalbuminuria (albumin excretion rate >300 mg/g creatinine). To investigate the role of the α-globin gene microdeletion and β-globin gene cluster haplotypes on the degree of glomerular involvement, 76 adult SSA patients (hemoglobin SS) were studied to determine the relationship between these genetic markers and the development of sickle cell glomerulopathy. Macroalbuminuria was present in 22 (29%) of 76 adult SSA patients. The coinheritance of microdeletions in one or two of the four α-globin genes (α-thalassemia) was associated with a lower prevalence of macroalbuminuria (13%) versus patients with intact α-globin genes (40%, P = 0.01). By contrast, there was no association between albuminuria and β-globin gene haplotypes (Central African Republic [CAR] versus non-CAR haplotypes). Patients with α-globin gene microdeletions had lower mean corpuscular volumes and mean corpuscular hemoglobin concentration than patients with all four α genes (86 ± 2 versus 99 ± 3 fl, and 33.9 ± 0.2 versus 34.9 ± 0.2%, respectively, P < 0.05). There were no such hematologic differences between CAR and non-CAR β-globin haplotypes. There were no differences in duration of disease (age), hemoglobin levels, reticulocyte index, and lactate dehydrogenase levels between those with and without glomerulopathy, but the mean arterial pressure was higher (87 ± 1 mmHg) in patients with intact α gene locus versus those with microdeletions (80 ± 2 mmHg, P < 0.05). It is concluded that the coinheritance of microdeletions in the α-globin gene locus in SSA patients confers “renoprotection” by mechanisms not related to the degree of anemia or the severity of hemolysis, but could be related to a reduced mean corpuscular volume or to a lower erythrocyte hemoglobin concentration.
Management of Bacteremia Associated with Tunneled-Cuffed Hemodialysis Catheters
Authors: BEATHARD GERALD A. 
Published: April 2021

Abstract.
The dominant problem associated with the use of tunneled-cuffed catheters is infection. When this occurs, two issues must be addressed: treatment of the infection and management of the catheter. The purpose of this 2-yr study was to report the results of a prospective observational series in which catheter management was based on the clinical picture presented by the patient. Data were collected on patients with catheter-related bacteremia (CRB) dealt with in one of three ways: (1) minimal symptoms with a normal-appearing tunnel and exit site (exchange over guidewire within 48 h of antibiotic initiation [Xchng group], 49 cases); (2) minimal symptoms but with tunnel or exit site infection (exchange over a guidewire with creation of a new tunnel [Nutunl group], 28 cases); and (3) severe clinical symptoms (catheter removal with delayed replacement after defervescence [Delay group], 37 cases). All cases were treated immediately with empiric antibiotics followed by 3 wk of antibiotic therapy based on culture sensitivities. A cure was defined as a 45-d symptom-free interval after antibiotic therapy was complete. A cure rate total of 87.8% for the Xchng group, 75% for the Nutunl group, and 86.5% for the Delay group was seen for the 114 episodes of CRB. It is concluded that in selected patients, catheter exchange over a guidewire within 48 h of antibiotic initiation followed by 3 wk of specific antibiotic therapy is a viable treatment option. Additionally, replacing the catheter in patients presenting with severe symptoms of sepsis as soon as they have defervesced is a reasonable approach to therapy.
Body Composition in Renal Transplant Patients
Authors: VAN DEN HAM EUGÉNIE C.H. , KOOMAN JEROEN P. , CHRISTIAANS MAARTEN H.L. , NIEMAN FRED H.M. , VAN KREEL BERNHARD K. , HEIDENDAL GUIDO A.K. , VAN HOOFF JOHANNES P. 
Published: April 2021

Abstract.
Whether multifrequency bioelectrical impedance analysis (MF-BIA), a relatively new method for measuring body composition, is also applicable for accurate body composition measurements in renal transplant (RTx) patients is not known. Therefore, the use of MF-BIA is validated in 77 RTx patients with a stable renal function at least 2 yr posttransplantation. MF-BIA is compared to isotope dilution techniques for measurement of body water compartments, and to dual energy x-ray absorptiometry (DEXA) and anthropometry for measurement of fat and fat free mass. Finally, DEXA and anthropometry are compared to each other. Method agreement is assessed by intraclass correlation coefficients (ICC) and plotted by Bland and Altman analysis. MF-BIA significantly underestimates total body water (TBW, 0.7 ± 2.1 L) and overestimates the extracellular water (ECW, 3.3 ± 1.8 L) compared to isotope dilution; the ICC between both techniques is 0.943 for TBW and 0.846 for ECW. The percentage body fat (BF) measured by MF-BIA is significantly higher than both BF measured by DEXA (3.4 ± 4.7%) or by anthropometry (5.5 ± 5.2%). The ICC between MF-BIA and DEXA is 0.887 and between MF-BIA and anthropometry 0.856. BF measured by DEXA is significantly higher than BF measured by anthropometry (2.1 ± 4.4%); their ICC is 0.913. In conclusion, MF-BIA seems to be suitable for measurement of TBW in RTx patients; however, method agreement between isotope dilution and MF-BIA for the measurement of ECW is not satisfactory. In the assessment of fat and fat free mass, the reliability of MF-BIA appears to be questionable. Method agreement between DEXA and anthropometry seems to be slightly better.
Polyomavirus Infection of Renal Allograft Recipients
Authors: NICKELEIT VOLKER , HIRSCH HANS H. , BINET ISABELLE F. , GUDAT FRED , PRINCE OLIVER , DALQUEN PETER , THIEL GILBERT , MIHATSCH MICHAEL J. 
Published: April 2021

Abstract.
Polyomavirus (PV) exceptionally causes a morphologically manifest renal allograft infection. Five such cases were encountered in this study, and were followed between 40 and 330 d during persistent PV renal allograft infection. Transplant (Tx) control groups without PV graft infection were analyzed for comparison. Tissue and urine samples were evaluated by light microscopy, immunohistochemistry, electron microscopy, and PCR. The initial diagnosis of PV infection with the BK strain was made in biopsies 9 ± 2 mo (mean ± SD) post-Tx after prior rejection episodes and rescue therapy with tacrolimus. All subsequent biopsies showed persistent PV infection. Intranuclear viral inclusion bodies in epithelial cells along the entire nephron and the transitional cell layer were histologic hallmarks of infection. Affected tubular cells were enlarged and often necrotic. In two patients, small glomerular crescents were found. In 54% of biopsies, infection was associated with pronounced inflammation, which had features of cellular rejection. All patients were excreting PV-infected cells in the urine. PV infection was associated with 40% graft loss (2 of 5) and a serum creatinine of 484 ± 326 μmol/L (mean ± SD; 11 mo post-Tx). Tx control groups showed PV-infected cells in the urine in 5%. Control subjects had fewer rejection episodes (P < 0.05) and stable graft function (P = 0.01). It is concluded that a manifest renal allograft infection with PV (BK strain) can persist in heavily immunosuppressed patients with recurrent rejection episodes. PV mainly affects tubular cells and causes necrosis, a major reason for functional deterioration. A biopsy is required for diagnosis. Urine cytology can serve as an adjunct diagnostic tool.
Regulation of Thick Ascending Limb Ion Transporter Abundance in Response to Altered Acid/Base Intake
Authors: KIM GHEUN-HO , ECELBARGER CAROLYN , KNEPPER MARK A. , PACKER RANDALL K. 
Published: April 2021

Abstract.
Changes in ammonium excretion with acid/base perturbations are dependent on changes in medullary ammonium accumulation mediated by active NH4
+ absorption by the medullary thick ascending limb. To investigate whether alterations in the abundance of medullary thick ascending limb ion transporters, namely the apical Na+/K+(NH4
+)/2Cl--cotransporter (BSC-1), the apical Na+/H+-exchanger (NHE3), and the Na+/K+-ATPase α1-subunit, may be responsible in part for altered medullary ammonium accumulation, semiquantitative immunoblotting studies were performed using homogenates from the inner stripe of the rat renal outer medulla. After 7 d of NH4Cl (7.2 mmol/220 g body wt per d) loading (associated with increased medullary ammonium accumulation), neither BSC-1 nor Na+/K+-ATPase protein expression was altered, but NHE3 protein abundance was significantly increased. On the other hand, both BSC-1 and Na+/K+-ATPase protein abundance was increased significantly in rats fed NaHCO3 (7.2 mmol/220 g body wt per d) for 7 d. Rats fed a high-NaCl diet (7.7 mEq Na+/220 g body wt per d) for 5 d also showed marked increases in both BSC-1 and Na+/K+-ATPase expression. The expression level of NHE3 protein did not change with either NaHCO3 or high NaCl intake. None of these three transporters showed a significant difference in abundance between the groups fed equimolar (7.2 mmol/220 g body wt per d for 7 d) NaHCO3 or NaCl. It is concluded that outer medullary BSC-1 and Na+/K+-ATPase α1-subunit protein abundance is increased by chronic Na+ loading but not by acid/base perturbations and that outer medullary NHE3 protein abundance is increased by chronic NH4Cl loading.
Dual Effect of Nitric Oxide Donors on Cyclooxygenase-2 Expression in Human Mesangial Cells
Authors: DÍAZ-CAZORLA MANUELA , PÉREZ-SALA DOLORES , LAMAS SANTIAGO 
Published: April 2021

Abstract.
Nitric oxide (NO) is emerging as a key regulator of gene expression, capable of playing either positive or negative roles. The results of this study indicate that NO exerts a dual effect on cyclooxygenase-2 (COX-2) expression in human mesangial cells (HMC). Treatment of HMC with NO synthase inhibitors attenuated interleukin-1β (IL-1β)/tumor necrosis factor-α (TNF-α)-elicited COX-2 protein and mRNA expression, suggesting a positive role of endogenous NO on COX-2 induction. However, NO donors (sodium nitroprusside [SNP] and S-nitroso-N-acetylpenicillamine [SNAP]) amplified cytokine-elicited COX-2 expression at early time points of treatment (up to 8 h for mRNA and up to 24 h for protein expression), but were inhibitory at later times. Oligonucleotide decoy experiments confirmed the importance of nuclear factor κB (NF-κB) activation for COX-2 induction by IL-1β/TNF-α. Treatment with N
G-nitro-L-arginine methyl ester (L-NAME) did not affect initial activation of NF-κB by IL-1β/TNF-α, but unveiled an inhibitory effect of NO generation on NF-κB activity after 4 h. In HMC supplemented with SNP, cytokine-induced NF-κB activation was potentiated at early times of induction (5 to 15 min), but inhibited at later times (1 to 4 h), suggesting a dual effect of NO donors on NF-κB activation. Interestingly, IκBα protein levels followed a reciprocal pattern of expression: IκBα levels were lower at early times of induction in NO donor-supplemented cells; however, after 1 h of treatment, IκBα levels became higher than in cells treated only with cytokines. In the presence of SNP, cytokine-elicited IκBα mRNA induction was initially delayed, but was amplified at later times. These changes in IκBα expression could contribute to the dual effects of NO donors on NF-κB activation and COX-2 expression in HMC.
Relationship between Kidney Size, Renal Injury, and Renal Impairment Induced by Shock Wave Lithotripsy
Authors: WILLIS LYNN R. , EVAN ANDREW P. , CONNORS BRET A. , BLOMGREN PHIL , FINEBERG NAOMI S. , LINGEMAN JAMES E. 
Published: April 2021

Abstract.
The relationship between kidney size and impaired renal function induced by shock-wave lithotripsy (SWL) was examined in 6- and 10-wk-old anesthetized pigs. Each pig received 2000 shock waves, 24 kV, or sham SWL to the lower pole calyx of one kidney. Bilateral GFR, renal plasma flow (RPF), and para-aminohippurate extraction was measured 1 h before and 1 and 4 h after SWL. The kidneys were then removed for morphometric analysis. Mean kidney weights were 66.1 ± 2.7 g (n = 9) and 103.1 ± 3.3 g (n = 8) in the SWL groups, and 60.1 ± 2.6 g (n = 9) and 82.3 ± 4.0 g (n = 9) in the sham-SWL groups. SWL-induced lesions occupied a significantly greater volume of the small kidneys (6.1 ± 1.7 vol % versus 1.5 ± 0.2 vol % in the large kidneys). RPF was significantly reduced by SWL in small and large kidneys, but to a significantly greater extent in small kidneys. RPF was also significantly reduced in the contralateral kidneys of both groups, but only at 1 h after SWL. SWL significantly reduced GFR to similar degrees in both kidneys of both groups, regardless of kidney size. Para-aminohippurate extraction was likewise reduced to similar degrees in both groups, but this effect was evident only in the SWL-treated kidneys, and only in the pole to which the shock waves had been applied. The injury induced by SWL affected a larger fraction of small kidneys than large ones, and the renal vasoconstriction induced by SWL was greatest in small kidneys.
Effect of Increasing Baseline Immunosuppression on the Prevalence of Clinical and Subclinical Rejection
Authors: NICKERSON PETER , JEFFERY JOHN , GOUGH JAMES , GRIMM PAUL , MCKENNA RACHEL , BIRK PATRICIA , RUSH DAVID 
Published: April 2021

Abstract.
This group has reported that treatment of subclinical rejection in the first 3 mo posttransplant with corticosteroids decreases late clinical rejections and improves graft function at 2 yr in renal transplant recipients. The current study was performed to determine whether an increase in baseline immunosuppression would decrease the prevalence of early subclinical rejections, as well as the incidence of early and late clinical rejections. Patients received mycophenolate mofetil (MMF) and Neoral cyclosporin A (CsA) posttransplant (n = 29), of which 17 underwent protocol biopsies at months 1, 2, 3, and 6 (Neoral + MMF Protocol Biopsy [Bx]), while 12 declined protocol biopsies (Neoral + MMF Control). These individuals were compared with 72 historical control patients treated with Sandimmune CsA and Imuran, of which 36 had undergone protocol biopsies at months 1, 2, 3, and 6 (Sandimmune + Azathioprine [AZA] Protocol Bx), and 36 had a protocol biopsy at month 6 (Sandimmune + AZA Control). Baseline immunosuppression with Neoral + MMF decreased the incidence of early clinical rejections (0 to 3 mo) and cumulative corticosteroid exposure, but had no impact on the prevalence of early subclinical rejection. Moreover, to maximally decrease the risk of developing late clinical rejections (months 7 to 12) in Neoral + MMF patients required that protocol biopsies be done and that subclinical rejection be treated. The paradoxical finding of recent clinical trials that a reduction in acute clinical rejection has not improved long-term graft outcome may be explained in part by the failure to control subclinical rejection.
The Luminal P2Y Receptor in the Isolated Perfused Mouse Cortical Collecting Duct
Authors: DEETJEN PHILIPP , THOMAS JO[Combining Diaeresis]RG , LEHRMANN HEIKO , KIM SUNG JOON , LEIPZIGER JENS 
Published: April 2021

Abstract.
Extracellular nucleotides regulate renal ion transport. With the use of in vitro perfusion and [Ca2+]i imaging, this study investigated whether mouse and rabbit cortical collecting ducts (CCD) respond to luminal nucleotides. In mouse CCD, luminal ATP (EC50: 10 μM) and UTP (EC50: 9.7 μM) increased [Ca2+]i with an initial peak and a plateau. To make certain that basolateral P2 receptors were not activated by luminal nucleotides via leak diffusion, luminal trypsin (1 μM), a known agonist for basolateral proteinase-activated receptors, was perfused. Mouse CCD that were responsive to luminal ATP were nonresponsive to luminal trypsin but always showed [Ca2+]i elevations by basolateral trypsin (10 or 100 nM). Luminal α,β- and β,γ-methylene ATP, 2-methyl-S-ATP, ADP, UDP, and 2′,3′-O-4-benzoylbenzoyl ATP had no effect (100 μM, n = 9). Without external Ca2+, luminal ATP still stimulated a [Ca2+]i increase. Mouse CCD also responded to basolateral ATP (EC50: 23 μM) and UTP (EC50: 23 μM) with smaller [Ca2+]i elevations. Confocal microscopy of perfused CCD showed that luminal ATP (100 μM) rapidly increased [Ca2+]i in nearly all cells (n = 6) and the same cells that responded to luminal ATP responded to basolateral ATP (100 μM). In contrast, rabbit CCD did not respond to luminal ATP/UTP (n = 8) despite ATP's known effect from the basolateral side (EC50: 34 μM). These data indicate the expression of luminal P2Y receptors (probably P2Y2) in principal cells of mouse CCD but not in rabbit CCD.
Inducible Nitric Oxide Synthase Attenuates Endothelium-Dependent Renal Microvascular Vasodilation
Authors: ICHIHARA ATSUHIRO , HAYASHI MATSUHIKO , NAVAR L. GABRIEL , SARUTA TAKAO 
Published: April 2021

Abstract.
Previous studies have demonstrated that inducible nitric oxide synthase (iNOS) plays a key pathophysiologic role during sepsis. The present study was designed to delineate the consequences of iNOS activation on renal microvascular function. Male Sprague-Dawley rats were given intraperitoneal injections of lipopolysaccharide (LPS; 4 mg/kg) at 16 h and 4 h before experimentation. Afferent and efferent arteriolar diameters from LPS-treated and control rats were assessed in vitro with the use of the blood perfused juxtamedullary nephron technique. Basal afferent and efferent arteriolar diameters of LPS-treated rats averaged 19.7 ± 0.9 (n = 7) and 18.3 ± 1.0 μm (n = 5), respectively, and were similar to those of control rats (20.8 ± 0.3 [n = 6] and 18.4 ± 0.6 μm [n = 6], respectively). Superfusion with the selective iNOS inhibitor S,S′-(1,3-phenylenebis[1,2-ethanediyl]) bisisothiourea (PBIT), at the doses of 0.01, 0.1, and 1 μM, significantly decreased afferent and efferent arteriolar diameters in a dose-dependent manner, whereas afferent or efferent arteriolar diameters of control rats were not altered in response to the same doses of PBIT. In the second series of experiments, superfusion with 10 μM acetylcholine (ACh) significantly increased afferent and efferent arteriolar diameters of LPS-treated rats by 14.9 ± 1.6% (n = 9) and 6.6 ± 1.1% (n = 6), respectively. The ACh-induced afferent and efferent arteriolar dilator responses were inhibited by superfusion with the nonselective NOS inhibitor N
ω-nitro-L-arginine (100 μM). However, afferent and efferent arteriolar dilator responses to ACh were significantly enhanced during selective iNOS inhibition with 1 μM PBIT (40.1 ± 0.7% and 25.2 ± 1.3%, respectively). These results suggest that activation of iNOS by LPS increases the influence of nitric oxide on afferent and efferent arteriolar tone and impairs endothelium-dependent nitric oxide effects.