bluuebunny/crossref_metadata_2025_split huggingface dataset:
Thrombotic Microangiopathy Associated with Parvovirus B 19 Infection after Renal Transplantation
Authors: MURER LUISA , ZACCHELLO GRAZIELLA , BIANCHI DANIELA , DALL'AMICO ROBERTO , MONTINI GIOVANNI , ANDREETTA BARBARA , PERINI MARINO , DOSSI ELISABETTA CURRO[Combining Grave Accent] , ZANON GIANFRANCO , ZACCHELLO FRANCO 
Published: April 2021

Abstract.
Human parvovirus B19 is considered an etiologic agent of aplastic anemia in immunosuppressed patients. Microscopic vasculitis, with or without renal involvement, has recently been attributed to this viral infection in immunocompetent patients. This study describes four cases of thrombotic renal graft microangiopathy presumably secondary to B19 infection. Twelve to 50 days after transplantation, four patients presented a renal graft dysfunction with creatinine rising to 360 to 1088 μmol/L and requiring hemodialysis in three cases. Renal involvement appeared after a systemic illness characterized by fever, fatigue and arthralgia, aplastic anemia (hemoglobin ranged from 5.3 to 7.8 g/dl), and thrombocytopenia. A thrombotic microangiopathy was observed in the renal biopsies, and the parvovirus B19 genome was isolated by PCR from the specimens. All four patients also became IgM-positive for parvovirus. Three of the four renal biopsies taken at the time of transplantation (T0) from the same patients were found positive for the B19 genome. Graft function recovered, with resolution of the aplastic anemia, within 22 to 110 d. Twenty biopsies performed as routine controls or for suspected acute rejection and nine T0 biopsies of patients with no signs of B19 infection were used. The B19 genome was found in two of 20 posttransplant biopsies and in one of nine T0 biopsies. The temporal association between aplastic anemia and the onset of thrombotic graft microangiopathy, isolation of the viral genome in renal specimens, seroconversion, and endothelial tropism of the virus suggests that B19 could be the etiologic agent of thrombotic microangiopathy in these cases. The development of the disease after infection could depend on other detrimental cofactors, which make the patient more susceptible to microthrombi formation in the renal microvasculature. The renal graft could represent the route of B19 transmission.
Localization of the Epithelial Ca2+ Channel in Rabbit Kidney and Intestine
Authors: HOENDEROP JOOST G. J. , HARTOG ANITA , STUIVER MARCHEL , DOUCET ALAIN , WILLEMS PETER H. G. M. , BINDELS RENÉ J. M. 
Published: April 2021

Abstract.
The epithelial Ca2+ channel (ECaC), which is exclusively expressed in 1,25-dihydroxyvitamin D3-responsive tissues, i.e., kidney, intestine, and placenta, is postulated to constitute the initial step in the process of transcellular Ca2+ transport. To strengthen this postulated function, the present study compares the segmental and cellular distribution of ECaC and the other Ca2+ transport proteins known to be involved in transcellular Ca2+ transport. In rabbit kidney, ECaC mRNA and protein expression were primarily present in the connecting tubule. Immunopositive staining for the ECaC protein was exclusively found at the apical domain of this tubular segment. Importantly, ECaC completely colocalized with calbindin-D28K, Na+-Ca2+ exchanger (NCX), and plasma membrane Ca2+ -ATPase (PMCA). A minority of cells along the distal tubule lacked immunopositive staining for ECaC and the other Ca2+ transporting proteins. These negative cells were identified as intercalated cells. In intestine, ECaC was present in a thin layer along the apical membrane of the duodenal villus tip, whereas the crypt and goblet cells were negative. Again, a complete colocalization was observed between ECaC, calbindin-D9K, and PMCA. In contrast to the kidney, NCX could not be detected in duodenum. The present finding that ECaC completely colocalizes with the Ca2+ transport proteins in the connecting tubule and duodenum, together with its apical localization, further substantiates the postulated function of ECaC as the gatekeeper of active Ca2+ (re)absorption.
Exaggerated Impact of ATP-Sensitive K+ Channels on Afferent Arteriolar Diameter in Diabetes Mellitus
Authors: IKENAGA HIDEKI , BAST JOSEPH P. , FALLET RACHEL W. , CARMINES PAMELA K. 
Published: April 2021

Abstract.
Experiments were performed to determine the involvement of ATP-sensitive K+ channels (KATP channels) in the renal afferent arteriolar dilation that occurs during the hyperfiltration stage of insulin-dependent diabetes mellitus (IDDM). IDDM was induced in rats by streptozotocin (STZ) injection, and adequate insulin was provided to maintain moderate hyperglycemia. Sham rats received vehicle treatments. Two weeks later, afferent arteriolar function was assessed using the in vitro blood-perfused juxtamedullary nephron technique. Baseline afferent arteriolar lumen diameter was greater in STZ rats (25.9 ± 1.1 μm) than in sham rats (20.8 ± 1.0 μm). Glibenclamide (3 to 300 μM) had virtually no effect on afferent arterioles from sham rats; however, this KATP antagonist caused concentration-dependent afferent arteriolar constriction in kidneys from STZ-treated rats, restoring lumen diameter to 20.6 ± 1.7 μm (P > 0.05 versus sham baseline). In both groups of rats, pinacidil (a cyanoguanidine KATP agonist; 0.3 to 300 μM) evoked concentration-dependent afferent arteriolar dilation, indicating the functional expression of KATP channels; however, lumen diameter was increased by 73% in STZ kidneys but only by 48% in sham kidneys. The gliben-clamide-sensitive afferent arteriolar dilator response to 1 μM PCO-400 (a benzopyran KATP agonist) was also accentuated in STZ kidneys. These observations suggest that increases in both the functional availability and basal activation of KATP channels promote afferent arteriolar vasodilation during the early stage of IDDM, changes that likely contribute to the etiology of diabetic hyperfiltration.
Bradykinin B1 Receptor-Mediated Changes in Renal Hemodynamics during Endotoxin-Induced Inflammation
Authors: SCHANSTRA JOOST P. , MARIN-CASTAN[Combining Tilde]O MARIA E. , PRADDAUDE FRANC[COMBINING CEDILLA]OISE , TACK IVAN , ADER JEAN-LOUIS , GIROLAMI JEAN-PIERRE , BASCANDS JEAN-LOUP , JEUNIER BENOIT 
Published: April 2021

Abstract.
Kinins have been shown to influence renal hemodynamics and function. Under physiologic conditions, most kinin effects involve bradykinin B2 receptors, but bradykinin B1 receptors are often induced during inflammation. The purpose of this study was to examine in vivo the effects of bradykinin B1 receptor activation on renal hemodynamics under normal and inflammatory conditions. In anesthetized rats, activation of bradykinin B1 receptors by arterial infusion of bradykinin B1 receptor agonist des-Arg9-bradykinin reduced renal plasma flow and GFR. Prior administration (18 h) of lipopolysaccharide to induce inflammation resulted in a larger bradykinin B1 receptor-induced reduction in renal plasma flow. Values of other parameters remained unchanged, thus resulting in an increased filtration fraction. The presence and the functionality of the bradykinin B1 receptor at the level of glomerular afferent and efferent arterioles were studied by mRNA expression analysis and intracellular calcium ([Ca2+]i) mobilization studies. Stimulation with des-Arg9-bradykinin of microdissected afferent arterioles from control and lipopolysaccharide-treated rats induced [Ca2+]i mobilization without any significant difference in amplitude between control and lipopolysaccharidetreated rats. However, des-Arg9-bradykinin only induced [Ca2+]i mobilization in efferent arterioles from lipopolysaccharide-treated rats. It is suggested that activation of bradykinin B1 receptors located along the efferent arteriole may participate in the modification of renal hemodynamics in inflammatory states.
The Affinity of the Organic Cation Transporter rOCT1 Is Increased by Protein Kinase C-Dependent Phosphorylation
Authors: MEHRENS THOMAS , LELLECK SILKE , C[COMBINING CEDILLA]ETINKAYA IBRAHIM , KNOLLMANN MARION , HOHAGE HELGE , GORBOULEV VALENTIN , BOKNÍK PETER , KOEPSELL HERMANN , SCHLATTER EBERHARD 
Published: April 2021

Abstract.
Members of the organic cation transporter (OCT) family are mainly expressed in kidney, liver, intestine, and brain. The regulation of the OCT type 1 from rat (rOCT1) stably transfected in HEK293 cells was examined using a fluorimetric technique, 1-[3H]methyl-4-phenylpyridinium uptake studies, and fast-whole-cell patch-clamp recordings. For the fluorescence measurements, the cation 4-(4-(dimethylamino)styryl)-N-methylpyridinium iodide (ASP+) was used as substrate. Uptake of ASP+ via rOCT1 was electrogenic, and its inhibition by other organic cations was consistent with previously reported radioactive tracer flux measurements. The inhibitor quinine was not translocated by the organic cation transporter in contrast to tetraethylammonium. Stimulation of diacyl glycerol-dependent protein kinase C (PKC) by sn-1,2-dioctanoyl glycerol (1 μM) resulted in an increase in initial ASP+ uptake rate by 216 ± 28% (n = 29). The effect was completely antagonized by the PKC inhibitor tamoxifen (20 μM, n = 22). Forskolin (1 μM), which activates adenylate cyclase and thereby protein kinase A (PKA), stimulated the initial rate of ASP+ accumulation by 51 ± 6% (n = 19). This effect was inhibited by the specific PKA inhibitor KT5720 (1 μM, n = 12). Inhibition of tyrosine kinases by aminogenestein (10 μM) reduced ASP+ uptake by 63 ± 7% (n = 7), while genestein or tyrphostin AG1295 (each 10 μM) were without significant effects. Incubation of the cells with sn-1,2-dioctanoyl glycerol (1 μM) increased the affinities of the transporter to tetraethylammonium, tetrapenthylammonium, and quinine by a factor of 58, 14.5, and 2.4, respectively. Western blot analysis revealed that rOCT1 protein was phosphorylated at a serine residue upon stimulation of PKC. In conclusion, it has been demonstrated that the organic cation transport by rOCT1 is stimulated by PKC, PKA, and endogenous tyrosine kinase activation. The PKC phosphorylates rOCT1 and leads to a conformational change at the substrate binding site.
Renal Enlargement Precedes Renal Hyperfiltration in Early Experimental Diabetes in Rats
Authors: BAK MARTIN , THOMSEN KLAUS , CHRISTIANSEN THORA , FLYVBJERG ALLAN 
Published: April 2021

Abstract.
The order of appearance between renal hypertrophy and hyperfunction in early experimental diabetes is still disputed. The reason for previous discrepant results is believed to be methodologic problems, as most previous studies of renal function have been performed in anesthetized animals. In the present study in nondiabetic and streptozotocin-diabetic animals, renal volume was measured by a noninvasive magnetic resonance imaging technique, while renal function parameters were measured in conscious, chronically catheterized animals. To avoid artifacts caused by the procedures associated with induction of streptozotocin-diabetes (fasting, brief anesthesia, and transient hypoglycemia) on renal growth and function, diabetic animals were injected with insulin to obtain euglycemia for 4 d before study start. At day 0, insulin administration was withdrawn and all animals developed hyperglycemia within 12 h. Renal volume and kidney function were measured on days 0, 1, 2, 3, 5, and 7. Renal enlargement was detectable at day 1 (20%) and reached an increase of 40% at day 7. No changes were seen in effective renal plasma flow or effective renal vascular resistance within the first 7 d after development of hyperglycemia. GFR tended to rise on day 5 and was increased by 16% at day 7. The absolute proximal reabsorption showed a pronounced rise (30%) at day 7, whereas no change was seen in the proximal tubular fluid output. It is concluded that renal enlargement precedes renal hyperfunction in the early phase after onset of experimental diabetes.
Nitric Oxide Synthesis Inhibition Does Not Impair Water Immersion-Induced Renal Vasodilation in Humans
Authors: DIJKHORST-OEI LIOE-TING , BOER PETER , RABELINK TON J. , KOOMANS HEIN A. 
Published: April 2021

Abstract.
Nitric oxide (NO) is tonically released in the kidney to maintain renal perfusion and adequate sodium and water clearance. Little is known about the role of NO in the renal adaptation to an acute volume challenge. This is important for our understanding of pathophysiologic conditions associated with impaired NO activity. This study examined the effects of NO synthesis inhibition on neurohumoral, renal hemodynamic, and excretory responses to head-out immersion (HOI). Seven healthy men underwent four 7-h clearance studies. One study served as a time control study (placebo infusion), and in one study N
G-monomethyl-L-arginine (L-NMMA; 3 mg/kg priming dose + 3 mg/kg per h) was infused during hours 2 to 5. In a third and fourth clearance study, HOI was applied from hours 3 to 5, during infusion of either placebo or L-NMMA. To assess the degree of NO synthesis inhibition, the effect of L-NMMA on [15N]-arginine-to-[15N]-citrulline conversion rate was studied in four others. HOI decreased mean arterial pressure (MAP) from 87 ± 3 to 76 ± 2 mmHg and renal vascular resistance (RVR) from 82 ± 6 to 70 ± 7 mmHg · min/L, and increased sodium excretion (UNaV) from 110 ± 27 to 195 ± 29 μmol/min and flow (UV) from 14.4 ± 1.4 to 15.8 ± 1.4 ml/min. L-NMMA caused profound and sustained increases in MAP and RVR and decreases in UNaV and UV. HOI superimposed on L-NMMA infusion decreased the elevated MAP from 93 ± 4 to 83 ± 2 mmHg and RVR from 111 ± 9 to 95 ± 7 mmHg · min/L, and increased UNaV from 41 ± 8 to 95 ± 15 μmol/min and UV from 10.0 ± 1.1 to 12.7 ± 1.4 ml/min. The relative changes were not significantly different from the effects of HOI without L-NMMA infusion. HOI decreased plasma renin activity and aldosterone and increased plasma atrial natriuretic peptide and urinary cGMP. L-NMMA decreased urinary cGMP, but did not affect the plasma hormones or the changes induced by HOI. L-NMMA decreased the [15N]-arginine-to-[15N]-citrulline conversion rate to one-third of baseline. The results indicate that in a state of NO deficiency in humans, the kidney can still respond to an acute volume challenge with vasorelaxation, diuresis, and natriuresis.
Minimizing Hemodialysis Vascular Access Trauma with an Improved Needle Design
Authors: ROSS EDWARD A. , VERLANDER JILL W. , KOO LILIA C. , HAWKINS IRVIN F. 
Published: April 2021

Abstract.
The maintenance and longevity of hemodialysis vascular access remains one of the most problematic topics in the care of dialysis patients. Although much attention has focused on neointimal hyperplasia, the repetitive trauma to vessel walls by dialysis needles causes significant cumulative damage that has undergone little investigation. Commercial needles have beveled tips with intentional cutting surfaces to ease insertion. It was hypothesized that a pencil-point conical-shaped needle would cause less damage by taking advantage of the elasticity of native fistulae and produce an improved hole configuration in synthetic materials with minimal ability to stretch. A needle was subsequently designed with a removable pencil-point trocar and a side arm for the dialysis tubing. Once the trocar is removed, the blunt-ended cannula can be advanced or can be subject to inadvertent motion without causing damage to the luminal surface of the access. The new design as well as standard 15-gauge hemodialysis needles were tested on Gore-Tex® graft material and two bovine carotid artery preparations. Scanning electron microscopy was used to study the hole patterns. For all materials, the commercial needle holes had typical crescent shapes, and the cuts sliced sequentially through the various layers. For grafts, the new design caused a linear defect parallel to the axis of the graft that may preserve longitudinal strength. Interestingly, that tear line was nearly perpendicular to the linear hole in the thin polytetrafluoroethylene overwrap, which would be consistent with maintenance of hoop integrity. It is believed that these nonoverlapping defects would also improve hemostasis. The bovine specimens tested the importance of tissue stretching: Fresh carotid artery had experimental holes dramatically smaller than those from standard needles. In the denatured tissue, the experimental needle provided less benefit than that observed in fresh tissue, which is likely due to limited elasticity of the preserved artery. Improvement in needle design thus provides distinct advantages for native vessels and unique less traumatic holes in current synthetic materials. Pencil-point needle designs may be particularly applicable to the development of new elastomeric graft material.
From Tonus to Tonicity
Authors: WALDEGGER SIEGFRIED , JENTSCH THOMAS J. 
Published: April 2021

Abstract.
Chloride channels are involved in a multitude of physiologic processes ranging from basal cellular functions such as cell volume regulation and acidification of intracellular vesicles to more specialized mechanisms such as vectorial transepithelial transport and regulation of cellular excitability. This plethora of functions is accomplished by numerous functionally highly diverse chloride channels that are only partially identified at the molecular level. The CLC family of chloride channels comprises at present nine members in mammals that differ with respect to biophysical properties, cellular compartmentalization, and tissue distribution. Their common structural features include a predicted topology model with 10 to 12 transmembrane regions together with two C-terminal CBS domains. Loss of function mutations affecting three different members of the CLC channel family lead to three human inherited diseases: myotonia congenita, Dent's disease, and Bartter's syndrome. These diseases, together with the diabetes insipidus symptoms of a knockout mouse model, emphasize the physiologic relevance of this ion channel family.
Effects of Low Dose Sympathetic Inhibition on Glomerulosclerosis and Albuminuria in Subtotally Nephrectomized Rats
Authors: AMANN KERSTIN , RUMP LARS CHRISTIAN , SIMONAVICIENE AURELIA , OBERHAUSER VITUS , WESSELS SABINE , ORTH STEPHAN R. , GROSS MARIE-LUISE , KOCH ANDREAS , BIELENBERG GERHARD W. , VAN KATS JORGE P. , EHMKE HEIMO , MALL GERHARD , RITZ EBERHARD 
Published: April 2021

Abstract.
A potential role of the sympathetic nervous system in progression of renal failure has received little attention. This study examined whether nonhypotensive doses of moxonidine, an agent that reduces sympathetic activity, affects glomerulosclerosis, urine albumin excretion, and indices of renal handling of norepinephrine (NE) in subtotally nephrectomized (SNX) rats. Sprague Dawley rats were SNX or sham-operated (control). SNX rats were either left untreated or treated with moxonidine in a dose (1.5 mg/kg body wt per d) that did not modify telemetrically monitored 24-h BP. Glomerular and renal morphology were evaluated by quantitative histology, immunohistochemistry, and in situ hybridization. Urine albumin excretion rate was analyzed by enzyme-linked immunosorbent assay, and kidney angiotensin II and NE content were measured using HPLC, 3H-NE uptake, and release. Body and kidney weight and BP were not significantly different between SNX with or without moxonidine. The glomerulosclerosis index was significantly lower in moxonidine-treated (0.88 ± 0.09) compared with untreated (1.55 ± 0.28) SNX rats, as was the index of vascular damage (0.32 ± 0.14 versus 0.67 ± 0.16). The number of proliferating cell nuclear antigen-positive glomerular and tubular cells per area was significantly higher in untreated SNX rats than in controls and moxonidine-treated SNX rats. The same was true for urine albumin excretion rate. Renal angiotensin II tissue concentration was not affected by moxonidine. In untreated SNX rats, renal nerve stimulation and exogenous NE induced an increase in isolated kidney perfusion pressure (102 ± 21 versus 63 ± 8 mmHg). Renal endogenous NE content was significantly lower in SNX rats than in controls (86 ± 14 versus 140 ± 17 pg/mg wet weight). Cortical uptake of [3H]-NE was not different, but cortical NE release was significantly higher in SNX rats than in controls. Reduced function of presynaptic inhibitory α-adreno-receptors is unlikely because an α2-adrenoceptor antagonist increased NE release. At subantihypertensive doses, moxonidine ameliorates renal structural and functional damage in SNX animals, possibly through central inhibition of efferent sympathetic nerve traffic. In kidneys of SNX rats, indirect evidence was found for increased activity of a reduced number of nerve fibers.
Dyadic Relationship Conflict, Gender, and Mortality in Urban Hemodialysis Patients
Authors: KIMMEL PAUL L. , PETERSON ROLF A. , WEIHS KAREN L. , SHIDLER NICOLE , SIMMENS SAMUEL J. , ALLEYNE SYLVAN , CRUZ ILLUMINADO , YANOVSKI JACK A. , VEIS JUDITH H. , PHILLIPS TERRY M. 
Published: April 2021

Abstract.
The effects of dyadic satisfaction and conflict have not been well defined in the hemodialysis (HD) population. The aim of this study was to determine whether the perception of decreased dyadic satisfaction was associated with mortality in patients treated with HD, and if so, whether there were different relationships between risk factors, and differential outcomes in men and women. A total of 174 HD patients, primarily African-Americans, involved in dyadic relationships for more than 6 mo had indices of dyadic satisfaction, depression, perception of illness effects, social support, behavioral compliance with the dialysis prescription, and plasma interleukin-1 (IL-1) and β-endorphin levels measured. Cox proportional hazards models assessed relative mortality risks. Patients' dyadic satisfaction scores correlated with β-endorphin levels. There was no correlation of IL-1 or β-endorphin with any psychosocial or behavioral compliance measure in the group as a whole. Correlations between psychosocial, medical, and neuroimmunologic variables were different in men and women. For women, dyadic satisfaction correlated with β-endorphin levels, depression, and perception of illness. Women with higher dyadic satisfaction and decreased dyadic conflict were at decreased mortality risk, but dyadic adjustment indices were unassociated with differential survival in the larger group of men. Correlations between neuroendocrine and immune markers are different in African-American male and female HD patients. Greater dyadic satisfaction and lower dyadic conflict are independently associated with decreased mortality in female African-American HD patients, of the same order of magnitude as medical risk factors. Such effects may be attributable to a relationship between dyadic satisfaction and conflict and health-related behaviors, or through an effect on neuroendocrine or immunologic status.