bluuebunny/crossref_metadata_2025_split huggingface dataset:
Intermittent versus Continuous Intraperitoneal Glycopeptide/Ceftazidime Treatment in Children with Peritoneal Dialysis-Associated Peritonitis
Authors: SCHAEFER FRANZ , KLAUS GÜNTER , MÜLLER-WIEFEL DIRK E. , MEHLS OTTO 
Published: April 2021

Abstract.
Intermittent intraperitoneal antibiotic administration appears as a practical and economical therapeutic concept in continuous peritoneal dialysis (CPD)-related peritonitis, but the equivalence of this principle with standard continuous treatment awaits confirmation by prospective, randomized clinical trials. This study evaluates the efficacy, safety, and clinical acceptance of an initial combination treatment including a glycopeptide (vancomycin or teicoplanin) and ceftazidime, each applied either intermittently or continuously, in a cohort of pediatric patients with CPD-related peritonitis. Patients randomized for continuous treatment received an intraperitoneal loading dose of glycopeptide and ceftazidime followed by maintenance doses added to each dialysate bag. In the intermittent treatment groups, the glycopeptide was administered in two loading doses 7 d apart, and ceftazidime during one dialysis cycle per day. Initial treatment response was evaluated after 60 h by the change in a Disease Severity Score and by the clinical decision to continue initial treatment. Of 152 patients observed for a total of 234 patient years, 90 patients developed 195 episodes of peritonitis (including 27 relapses within 4 wk after end of treatment). Dialysate cultures were positive in 83% of the episodes. In Gram-positive peritonitis (79% of culture-positive cases), the primary success (overall 95%) and relapse rates (21%) were not different between continuous and intermittent, or between vancomycin and teicoplanin treatment. Oversensitivity reactions occurred in three and ototoxicity in one vancomycin-treated patient, whereas no such side effects were observed with teicoplanin. Residual renal function declined during peritonitis episodes regardless of treatment modality. In Gram-negative peritonitis (18% of cases), intermittent ceftazidime treatment was less successful than continuous treatment according to clinical judgment (3 of 11 versus 10 of 14, P < 0.05), but not when rated by Disease Severity Score (8 of 11 versus 12 of 14). In conclusion, intermittent and continuous intraperitoneal treatment of CPD-related peritonitis with glycopeptides and ceftazidime is equally efficacious and safe when measured by objective clinical criteria. This contrasts with a strong tendency of clinicians to move from intermittent to continuous treatment in severe peritonitis.
Renal Thrombotic Microangiopathy Associated with Anticardiolipin Antibodies in Hepatitis C-Positive Renal Allograft Recipients
Authors: BAID SEEMA , PASCUAL MANUEL , WILLIAMS WINFRED W. , TOLKOFF-RUBIN NINA , JOHNSON STEPHEN M. , COLLINS BERNARD , CHUNG RAYMOND T. , DELMONICO FRANCIS L. , COSIMI A. BENEDICT , COLVIN ROBERT B. 
Published: April 2021

Abstract.
Hepatitis C virus (HCV) infection has been associated with de novo or recurrent membranoproliferative glomerulonephritis and acute transplant glomerulopathy in transplanted kidneys. Recently, anticardiolipin antibodies (ACA) have been linked with chronic HCV infection. A few reports have suggested an association between ACA and renal allograft thrombosis. This study examines the clinical and pathologic features of HCV-positive renal allograft recipients at our institution. From 1990 to 1996, 379 kidney transplants were performed. We identified 18 recipients (4.8%) with HCV-positive serology pretransplant. Determination of IgG and IgM ACA was performed by enzyme-linked immunosorbent assay, using pretransplant sera. Among the 18 patients, five patients presented with biopsy-proven de novo renal thrombotic microangiopathy (RTMA), occurring 5 to 120 d (median, 14 d) after transplant. No differences in pretransplant characteristics were observed between patients with (n = 5) or without (n = 13) RTMA. All five patients had a positive ACA test (either IgG or IgM titer > 2 SD above normal), compared with only one of 13 patients without RTMA. The mean value for IgG ACA was significantly higher in the RTMA patients than in patients without RTMA (22.9 ± 14.1 versus 6.9 ± 4.9 IgG phospholipid units, P = 0.02); however, there were no significant differences in IgM ACA titers. Rheumatoid factor and complement C4 levels were normal in pretransplant sera of patients with RTMA. Patients with RTMA had their cyclosporine withdrawn (four of five) or the dose was decreased (one of five), and one of five underwent plasmapheresis. Four of five patients died within 5 yr after transplant, compared with no deaths in the other 13 patients. Finally, as a control group, seven HCV-negative renal allograft recipients who presented with RTMA/hemolytic uremic syndrome during the same time period were found to have normal ACA values (IgG or IgM). RTMA associated with ACA in HCV-positive renal allograft recipients may represent a new clinical entity. The occurrence of this syndrome may have deleterious consequences for patient and graft survival.
The Role of Selectins in Glomerular Leukocyte Recruitment in Rat Anti-Glomerular Basement Membrane Glomerulonephritis
Authors: DE VRIESE AN S. , ENDLICH KARLHANS , ELGER MARLIES , LAMEIRE NORBERT H. , ATKINS ROBERT C. , LAN HUI Y. , RUPIN ALAIN , KRIZ WILHELM , STEINHAUSEN MICHAEL W. 
Published: April 2021

Abstract.
Leukocytes play a central role in the pathogenesis of anti-glomerular basement membrane glomerulonephritis (anti-GBM GN). Understanding the mechanisms underlying their recruitment in the glomerulus is of critical importance, because this may lead to more specific anti-inflammatory drug design. The requirement for integrins, especially from the β2 group, and their Ig superfamily counter-receptors has been established, however, the role of selectins remains controversial. An intravital microscopy technique was developed to study concomitantly the glomerular and venular leukocyte kinetics and the hemodynamic alterations in a rat model of anti-GBM GN, induced by injection of 10 mg of nephrotoxic serum (NTS). Histologic studies of the kidney were performed in parallel and urinary protein excretion was measured. The animals received NTS alone or were pretreated with either a monoclonal antibody against the β2 integrin CD11b (OX42, 4 mg/kg) or fucoidan F7 (FF7, 8 mg/kg), an oligosaccharide that blocks both L- and P-selectin function. Administration of NTS resulted in a time-dependent increase in the number of adherent leukocytes in the glomeruli and a parallel decrease of the perfused glomerular capillary area. Substantial proteinuria was observed. Pretreatment with OX42 significantly attenuated these changes. FF7 almost abolished the rolling of the leukocytes in the venules, thus demonstrating efficient anti-selectin activity. Nevertheless, FF7 had no influence on the glomerular events or on the development of proteinuria. These results confirm that glomerular leukocyte adhesion in anti-GBM GN is CD11b-dependent. However, selectin-mediated interaction between the leukocytes and the glomerular capillary endothelium does not appear to be a prerequisite for leukocyte adhesion in the glomerulus. These results therefore question the potential utility of anti-selectin therapy in the treatment of anti-GBM GN.
Clinical and Pathologic Findings in Two New Allelic Murine Models of Polycystic Kidney Disease
Authors: VOGLER CAROLE , HOMAN SHARON , PUNG ALETHA , THORPE CONSTANCE , BARKER JANE , BIRKENMEIER EDWARD H. , UPADHYA POORNIMA 
Published: April 2021

Abstract.
Patients with inherited cystic kidney diseases have progressive cystic dilation of nephrons with concomitant loss of functional renal parenchyma and renal failure. Animal models of inherited cystic kidney disease are useful for study of the pathogenesis and molecular basis of cystic renal diseases. This article describes the clinical and pathologic features in two spontaneously occurring murine models of inherited polycystic kidney disease due to independent allelic mutations on mouse chromosome 8. The mutations, designated kat and kat2J
, affect a chromosomal segment homologous to a region of human chromosome 4q35; the altered gene has not yet been identified. An allelism test showed that the mutations are at the same locus. The phenotype, inherited as an autosomal recessive, is more severe in kat2J/kat2J
mice. Their kidneys are morphologically normal at birth, but by 3 mo of age, cysts affect all levels of the nephron. Adult males have testicular hypoplasia and they are sterile. A few of the oldest kat2J/kat2J
mice have focal portal bile duct proliferation and dilation. kat2J/kat2J
mice develop anemia and uremia and die before 1 yr of age. In kat/kat mice, the renal cystic disease progresses more slowly but is morphologically similar to that of kat2J/kat2J
mice. The progressive cystic transformation of the kidneys in these allelic murine models resembles that seen in humans with autosomal dominant polycystic kidney disease.
Glomerular Hyperfiltration in Experimental Diabetes Mellitus
Authors: VALLON VOLKER , RICHTER KERSTIN , BLANTZ ROLAND C. , THOMSON SCOTT , OSSWALD HARTMUT 
Published: April 2021

Abstract.
An increase in Na+/glucose cotransport upstream to the macula densa might contribute to the increase in single nephron GFR (SNGFR) in early diabetes mellitus by lowering the signal of the tubuloglomerular feedback, i.e., the luminal Na+, Cl-, and K+ concentration sensed by the macula densa. To examine this issue, micropuncture experiments were performed in nephrons with superficial glomeruli of streptozotocin-induced diabetes mellitus in rats. First, in nondiabetic control rats, ambient early distal tubular concentrations of Na+, Cl-, and K+ were about 21, 20, and 1.2 mM, respectively, suggesting collection sites relatively close to the macula densa. Second, glomerular hyperfiltration in diabetic rats was associated with a reduction in ambient early distal tubular concentrations of Na+, Cl-, and K+ by 20 to 28%, reflecting an increase in fractional reabsorption of these ions up to the early distal tubule. Third, in diabetic rats, early proximal tubular application of phlorizin, an inhibitor of Na+/glucose cotransport, elicited (1) a greater reduction in absolute and fractional reabsorption of Na+, Cl-, and K+ up to the early distal tubule, and (2) a greater increase in early distal tubular concentration of these ions, which was associated with a more pronounced reduction in SNGFR. These findings support the concept that stimulation of tubular Na+/glucose cotransport by reducing the tubuloglomerular feedback signal at the macula densa may contribute to glomerular hyperfiltration in diabetic rats. Glomerular hyperfiltration in diabetic rats serves to compensate for the rise in fractional tubular reabsorption to partly restore the electrolyte load to the distal nephron.
Immunohistochemical Localization of Multispecific Renal Organic Anion Transporter 1 in Rat Kidney
Authors: TOJO AKIHIRO , SEKINE TAKASHI , NAKAJIMA NORIKO , HOSOYAMADA MAKOTO , KANAI YOSHIKATSU , KIMURA KENJIRO , ENDOU HITOSHI 
Published: April 2021

Abstract.
Renal proximal convoluted tubules have an important role, i.e., to excrete organic anions, including numerous drugs and endogenous substances. Recently, multispecific organic anion transporter 1 (OAT1) was isolated from rat kidney. In this study, the cellular and subcellular localization of OAT1 in rat kidney was investigated. Kidneys from normal rats were perfused and fixed with periodate-lysine-paraformaldehyde solution and were then processed for immunohistochemical analysis using the labeled streptavidin-biotin method, preembedding horseradish peroxidase method, and immunogold method. Light microscopic examination revealed immunostaining for OAT1 in the middle portion of the proximal tubule (S2 segment), but not in the initial portion of the proximal convoluted tubule, next to the glomerulus. Nephron segments other than the S2 segment and the renal vasculature were not stained with antibody to OAT1. Electron-microscopic observation using a preembedding method revealed that OAT1 was exclusively expressed in the basolateral membrane of S2 segments of proximal tubules. The immunogold method showed no labeling for OAT1 in the cytoplasmic vesicles, suggesting that OAT1 may not move together with organic anions into the cells. These results are consistent with previous physiologic data showing that organic anions, including para-aminohippurate, are taken up by the basolateral Na+-independent organic anion/dicarboxylate exchanger and excreted at S2 segments. In conclusion, OAT1 was localized to the basolateral membrane of S2 segments of proximal tubules in rat kidneys.
Nodular Glomerulosclerosis with Deposition of Monoclonal Immunoglobulin Heavy Chains Lacking CH1
Authors: MOULIN BRUNO , DERET SOPHIE , MARIETTE XAVIER , KOURILSKY OLIVIER , IMAI HIROKAZU , DUPOUET LUC , MARCELLIN LUC , KOLB ISABELLE , AUCOUTURIER PIERRE , BROUET JEAN-CLAUDE , RONCO PIERRE M. , MOUGENOT BÉATRICE 
Published: April 2021

Abstract.
The objective of this study was to further characterize the clinical and immunopathologic features of heavy chain deposition disease (HCDD), a recently described entity. Four patients were diagnosed as having HCDD on a kidney biopsy. All presented with nodular glomerulosclerosis with deposition of γ1 heavy chains lacking CH1 epitopes, but without light chains. Two different patterns were observed in the serum. First, patients 1 and 2 had a circulating monoclonal IgGλ containing a short γ1 heavy chain lacking CH1 epitopes, with an apparent molecular weight of 40 kD consistent with a complete CH1 deletion. Biosynthetic experiments also showed that the deleted heavy chain was produced in excess compared with light chains, and was secreted in vitro together with half Ig molecules, although these abnormal components were not detected by Western blot analysis of whole serum. Second, patients 3 and 4 had a circulating monoclonal IgG1λ with an apparently normal, nondeleted heavy chain subunit, but serum fractionation followed by immunoblotting revealed an isolated monoclonal γ1 chain lacking CH1 epitopes. These data strongly suggest that renal deposition of a CH1-deleted heavy chain circulating in low amounts in the serum as a free unassembled subunit is a major feature of HCDD. The CH1 deletion is most likely responsible for the premature secretion in blood of the heavy chain by a clone of plasma cells.
Renal Function in High-Output Heart Failure in Rats
Authors: WILLENBROCK ROLAND , PAGEL INES , SCHEUERMANN MICHAELA , HÖHNEL KLAUS , MACKENZIE HARALD S. , BRENNER BARRY M. , DIETZ RAINER 
Published: April 2021

Abstract.
The physiologic and pathophysiologic importance of natriuretic peptides (NP) has been imperfectly defined. The diminished renal responses to exogenous atrial NP in heart failure have led to the perception that the endogenous NP system might be less effective and thus contribute to renal sodium retention in heart failure. This study tests the hypothesis that in experimental heart failure, the renal responses to an acute volume load are still dependent on the NP system. The specific antagonist HS-142-1 was used to block the effects of NP in a model of high-output heart failure induced by an aortocaval shunt. Plasma cGMP levels and renal cGMP excretion were significantly lower in shunted and sham-operated rats receiving HS-142-1, compared with vehicle-treated controls, indicating effective blockade of guanylate cyclase-coupled receptors. Baseline sodium excretion and urine flow rate were lower in HS-142-1-treated sham-operated rats (15.2 ± 1.1 μl/min versus 27.5 ± 3.1 μl/min with vehicle, P < 0.001) and in HS-142-1-treated shunted rats (8.1 ± 1.3 μl/min versus 19.9 ± 2.3 μl/min with vehicle, P < 0.001). After an acute volume load, the diuretic and natriuretic responses were attenuated by HS-142-1 in control and shunted rats. The renal responses were reduced by HS-142-1 to a significantly greater extent in shunted rats than in control rats. HS-142-1 did not induce any significant systemic hemodynamic changes in either group, nor did it alter renal blood flow. However, the GFR in HS-142-1-treated shunted rats was lower than that in vehicle-treated shunted rats, both at baseline (0.6 ± 0.3 ml/min versus 2.1 ± 0.4 ml/min with vehicle, P < 0.05) and after an acute volume load (1.2 ± 0.4 ml/min versus 2.6 ± 0.4 ml/min with vehicle, P = 0.01), whereas no such effect was observed in control rats. These data indicate that the maintenance of basal renal function and the responses to acute volume loading are dependent on the NP system. The NP seem to be of particular importance for the maintenance of GFR in this model of experimental heart failure. These observations provide new insights into the importance of the renal NP system in heart failure.
Hematocrit Level and Associated Mortality in Hemodialysis Patients
Authors: MA JENNIE Z. , EBBEN JIM , XIA HONG , COLLINS ALLAN J. 
Published: April 2021

Abstract.
Although a number of clinical studies have shown that increased hematocrits are associated with improved outcomes in terms of cognitive function, reduced left ventricular hypertrophy, increased exercise tolerance, and improved quality of life, the optimal hematocrit level associated with survival has yet to be determined. The association between hematocrit levels and patient mortality was retrospectively studied in a prevalent Medicare hemodialysis cohort on a national scale. All patients survived a 6-mo entry period during which their hematocrit levels were assessed, from July 1 through December 31, 1993, with follow-up from January 1 through December 31, 1994. Patient comorbid conditions relative to clinical events and severity of disease were determined from Medicare claims data and correlated with the entry period hematocrit level. After adjusting for medical diseases, our results showed that patients with hematocrit levels less than 30% had significantly higher risk of all-cause (12 to 33%) and cause-specific death, compared to patients with hematocrits in the 30% to less than 33% range. Without severity of disease adjustment, patients with hematocrit levels of 33% to less than 36% appear to have the lowest risk for all-cause and cardiac mortality. After adjusting for severity of disease, the impact of hematocrit levels of 33% to less than 36% is vulnerable to the patient sample size but also demonstrates a further 4% reduced risk of death. Overall, these findings suggest that sustained increases in hematocrit levels are associated with improved patient survival.
Physiology and Pathophysiology of Renal Aquaporinsa
Authors: NIELSEN SØREN , KWON TAE-HWAN , CHRISTENSEN BIRGITTE MØNSTER , PROMENEUR DOMINIQUE , FRØKIÆR JØRGEN , MARPLES DAVID 
Published: April 2021

Abstract.
The discovery of aquaporin membrane water channels by Agre and coworkers answered a long-standing biophysical question of how water specifically crosses biologic membranes, and provided insight, at the molecular level, into the fundamental physiology of water balance and the pathophysiology of water balance disorders. Of nine aquaporin isoforms, at least six are known to be present in the kidney at distinct sites along the nephron and collecting duct. Aquaporin-1 (AQP1) is extremely abundant in the proximal tubule and descending thin limb, where it appears to provide the chief route for proximal nephron water reabsorption. AQP2 is abundant in the collecting duct principal cells and is the chief target for vasopressin to regulate collecting duct water reabsorption. Acute regulation involves vasopressin-regulated trafficking of AQP2 between an intracellular reservoir and the apical plasma membrane. In addition, AQP2 is involved in chronic/adaptational regulation of body water balance achieved through regulation of AQP2 expression. Importantly, multiple studies have now identified a critical role of AQP2 in several inherited and acquired water balance disorders. This concerns inherited forms of nephrogenic diabetes insipidus and several, much more common acquired types of nephrogenic diabetes insipidus where AQP2 expression and/or targeting are affected. Conversely, AQP2 expression and targeting appear to be increased in some conditions with water retention such as pregnancy and congestive heart failure. AQP3 and AQP4 are basolateral water channels located in the kidney collecting duct, and AQP6 and AQP7 appear to be expressed at lower abundance at several sites including the proximal tubule. This review focuses mainly on the role of AQP2 in water balance regulation and in the pathophysiology of water balance disorders.
Evidence for an Essential Role of Megalin in Transepithelial Transport of Retinol
Authors: CHRISTENSEN ERIK ILSØ , MOSKAUG JAN ØIVIND , VORUM HENRIK , JACOBSEN CHRISTIAN , GUNDERSEN THOMAS E. , NYKJÆR ANDERS , BLOMHOFF RUNE , WILLNOW THOMAS E. , MOESTRUP SØREN K. 
Published: April 2021

Abstract.
Transepithelial transport of retinol is linked to retinol-binding protein (RBP), which is taken up and also synthesized in a number of epithelia. By immunocytochemistry of human, rat, and mouse renal proximal tubules, a strong staining in apical endocytic vacuoles, lysosomes, endoplasmic reticulum, Golgi, and basal vesicles was observed, in accordance with luminal endocytic uptake as well as a constitutive synthesis and basal secretion of RBP. Analysis of mice with target disruption of the gene for the major endocytic receptor of proximal tubules, megalin, revealed no RBP in proximal tubules of these mice. Western blotting and HPLC of the urine of the megalin-deficient mice instead revealed a highly increased urinary excretion of RBP and retinol, demonstrating that glomerular filtered RBP-retinol of megalin-deficient mice escapes uptake by proximal tubules. A direct megalin-mediated uptake of purified RBP-retinol was indicated by surface plasmon resonance analysis and uptake in immortalized rat yolk sac cells. Uptake was partially inhibited by a polyclonal megalin antibody and the receptor-associated protein. The present data show that the absence of RBP-binding megalin causes a significantly increased loss of RBP and retinol in the urine, demonstrating a crucial role of megalin in vitamin A homeostasis.
Natriuretic and Diuretic Actions of a Highly Selective Adenosine A1 Receptor Antagonist
Authors: WILCOX CHRISTOPHER S. , WELCH WILLIAM J. , SCHREINER GEORGE F. , BELARDINELLI LUIZ 
Published: April 2021

Abstract.
The natriuretic and diuretic action of a highly selective adenosine A1 receptor (A1AdoR) antagonist, 1,3-dipropyl-8-[2-(5,6-epoxy)norbornyl]xanthine (CVT-124), was investigated in anesthetized rats. CVT-124 (0.1 to 1 mg/kg) caused dose-dependent increases in urine flow and fractional and absolute sodium excretion of by six- to 10-fold and, at 0.1 mg/kg, increased the GFR (1.6 ± 0.1 to 2.5 ± 0.2 ml/min; P < 0.01). There were no changes in BP or heart rate. CVT-124 reduced absolute proximal reabsorption (26 ± 3 to 20 ± 2 nl/min; P < 0.05) despite unchanged proximally measured, single-nephron GFR (SNGFR) (42 ± 5 to 44 ± 4 nl/min; NS) and thereby decreased fractional proximal reabsorption (60 ± 3 to 46 ± 4%; P < 0.05). Despite increasing distal tubular fluid flow rate (5.4 ± 0.7 to 9.7 ± 0.9 nl/min; P < 0.001), it reduced the proximal-distal difference in SNGFR (before: 9.4 ± 1.0 versus during CVT-124: 4.6 ± 1.5 nl/min; P < 0.01), suggesting that it had blunted the effects of the macula densa on SNGFR. Direct measurements of maximal tubuloglomerular feedback (TGF) responses were made from proximal stop flow pressure (PSF) during orthograde loop perfusion from the proximal tubule with artificial tubular fluid at 40 nl/min. TGF was blunted by intravenous CVT-124 (0.5 mg/kg; ▵PSF with vehicle: 8.3 ± 0.6 versus CVT-124: 6.5 ± 0.3 mmHg; n = 9; P < 0.01). In conclusion, A1AdoR blockade reduces proximal reabsorption and uncouples it from glomerular filtration. It increases distal delivery of fluid yet does not activate a macula densa-dependent fall in SNGFR because it blunts the TGF response. Natriuresis accompanied by blockade of proximal glomerulotubular balance and TGF characterizes a new class of diuretic drugs.