bluuebunny/crossref_metadata_2025_split huggingface dataset:
Hemodynamic Patterns and Spectral Analysis of Heart Rate Variability during Dialysis Hypotension
Authors: BARNAS MICHEL G. W. , BOER WALTHER H. , KOOMANS HEIN A. 
Published: April 2021

Abstract.
Intradialytic hypotension, a major source of morbidity during hemodialysis and ultrafiltration, is often accompanied by paradoxical bradycardia. Relatively little is known about the sequential changes in autonomic nervous system activity up to and during the hypotensive episode. Continuous, beat-to-beat measurements of BP and heart rate were made during hemodialysis in patients prone (n = 8) and not prone (n = 11) to develop intradialytic hypotension. Off-line spectral analysis of heart rate variability (HRV) was performed to assess changes in autonomic nervous system activity during dialysis sessions both with and without hypotension. The low frequency (LF) component of HRV is thought to correlate with sympathetic nervous system activity, the high frequency (HF) component with that of the parasympathetic nervous system. In the sessions not complicated by symptomatic hypotension (n = 26), mean arterial BP (MAP) hardly fell, whereas heart rate increased from 77 ± 2 to 89 ± 5 bpm (P < 0.05). The LF component of HRV increased from 45.2 ± 5.0 normalized units (nu) to 59.9 ± 4.9 nu (P < 0.05), whereas the HF component fell from 54.8 ± 5.0 to 40.2 ± 4.4 nu (P < 0.05). These changes agree with compensatory baroreflex-mediated activation of the sympathetic nervous system (and suppressed parasympathetic activity) during ultrafiltration-induced intravascular volume depletion. In the sessions complicated by severe symptomatic hypotension (n = 22), the changes in heart rate and the results of spectral analysis of HRV were similar to those reported above up to the moment of sudden symptomatic (nausea, vomiting, dizziness, cramps) hypotension, whereas MAP had already fallen gradually from 94 ± 3 to 85 ± 3 mmHg (P < 0.05). The sudden further reduction in MAP (to 55 ± 2 mmHg, P < 0.02) was invariably accompanied by bradycardia (heart rate directly before hypotension 90 ± 2 bpm, during hypotension 69 ± 3 bpm, P < 0.002). The LF component of HRV fell from 62.8 ± 4.6 nu directly before to 40.0 ± 3.7 nu (P < 0.05) during hypotension, whereas the HF component increased from 37.9 ± 4.7 to 60.3 ± 3.7 nu (P < 0.05). These findings agree with activation of the cardiodepressor reflex, involving decreased sympathetic and increased parasympathetic nervous system activity, respectively. These findings indicate that activation of the sympatho-inhibitory cardiodepressor reflex (Bezold-Jarisch reflex), which is a physiologic response to a critical reduction in intravascular volume and cardiac filling, is the cause of sudden intradialytic hypotension.
Volume Stress-Induced Peritoneal Endothelin-1 Release in Continuous Ambulatory Peritoneal Dialysis
Authors: MORGERA STANISLAO , KUCHINKE SIMONE , BUDDE KLEMENS , LUN ANDREAS , HOCHER BERTHOLD , NEUMAYER HANS-HELLMUT 
Published: April 2021

Abstract.
In long-term peritoneal dialysis, functional deterioration of the peritoneal membrane is often associated with proliferative processes of the involved tissues leading to peritoneal fibrosis. In continuous ambulatory peritoneal dialysis (CAPD), failure to achieve target values for adequacy of dialysis is commonly corrected by increasing dwell volume; in case of ultrafiltration failure, osmolarity of the dialysate gets increased. In a prospective study, the impact of increasing dwell volume from 1500 ml to 2500 ml per dwell (volume trial) or changing the osmolarity of the dialysate from 1.36 to 3.86% glucose (hyperosmolarity trial) on the peritoneal endothelin-1 (ET-1) release was analyzed. ET-1 is known to exert significant proliferative activities on a variety of cell types leading to an accumulation of extracellular matrix. A highly significant difference in the cumulative peritoneal ET-1 synthesis was found between the low- and high-volume exchange, whereas differences in the hyperosmolarity setting were only moderate. Sixty minutes after initiating dialysis, the cumulative ET-1 synthesis was 2367 ± 1023 fmol for the 1500 ml versus 6062 ± 1419 fmol for the 2500 dwell (P < 0.0001) and 4572 ± 969 fmol versus 6124 ± 1473 fmol for the 1.36 and 3.86% glucose dwell (P < 0.05), respectively. In conclusion, increasing dwell volume leads to a strong activation of the peritoneal paracrine endothelin system. Because ET-1, apart from being a potent vasoactive peptide, contributes to fibrotic remodeling, this study indicates that volume stress-induced ET-1 release might contribute to structural alteration of the peritoneal membrane in long-term peritoneal dialysis.
Angiotensin II Receptor Type 1 Gene Expression in Human Glomerulonephritis and Diabetes Mellitus
Authors: WAGNER JÜRGEN , GEHLEN FRANK , CIECHANOWICZ ANDRZEJ , RITZ EBERHARD 
Published: April 2021

Abstract.
The renin-angiotensin system plays an important role in the progression of chronic renal disease. Although the expression of renin and angiotensin-converting enzyme in experimental and human renal disease has been well characterized, no information is available regarding human angiotensin type 1 (AT1) receptor expression. The net effect of renin depends on AT1 receptor expression, among other factors. Receptor expression was determined in renal biopsy samples (including all tissue components) and isolated glomeruli from patients with glomerulonephritis (GN) or diabetic nephropathy (non-insulin-dependent diabetes mellitus). Biopsy samples and isolated glomeruli from tumor-free tissue from tumor nephrectomies served as controls. Human AT1 receptor gene expression was determined by quantitative reverse transcription-PCR, using an AT1 receptor deletion mutant as the internal standard. In whole biopsy samples from 37 patients with various types of GN, AT1 receptor mRNA levels were lower, compared with nine control biopsy samples (P < 0.001). AT1 receptor mRNA levels were also significantly lower (P < 0.001) in eight samples from patients with diabetic nephropathy. In microdissected glomeruli, AT1 receptor gene expression was significantly lower in samples from patients (n = 22) with various types of GN, compared with 12 microdissected tumor nephrectomy control samples (P < 0.0023). It is concluded that AT1 receptor mRNA expression is low in glomeruli of patients with chronic renal disease. This may reflect a regulatory response to (inappropriately) high intrarenal angiotensin II concentrations.
Immunohistochemical Evidence for an Increased Oxidative Stress and Carbonyl Modification of Proteins in Diabetic Glomerular Lesions
Authors: SUZUKI DAISUKE , MIYATA TOSHIO , SAOTOME NOBORU , HORIE KATSUNORI , INAGI REIKO , YASUDA YOSHINARI , UCHIDA KOJI , IZUHARA YUKO , YAGAME MITSUNORI , SAKAI HIDETO , KUROKAWA KIYOSHI 
Published: April 2021

Abstract.
Advanced glycation end products (AGE) include a variety of protein adducts whose accumulation has been implicated in tissue damage associated with diabetic nephropathy (DN). It was recently demonstrated that among AGE, glycoxidation products, whose formation is closely linked to oxidation, such as carboxymethyllysine (CML) and pentosidine, accumulate in expanded mesangial matrix and nodular lesions in DN, in colocalization with malondialdehyde-lysine (MDA-lysine), a lipoxidation product, whereas pyrraline, another AGE structure whose deposition is rather independent from oxidative stress, was not found within diabetic glomeruli. Because CML, pentosidine, and MDA-lysine are all formed under oxidative stress by carbonyl amine chemistry between protein amino group and carbonyl compounds, their colocalization suggests a local oxidative stress and increased protein carbonyl modification in diabetic glomerular lesions. To address this hypothesis, human renal tissues from patients with DN or IgA nephropathy were examined with specific antibodies to characterize most, if not all, carbonyl modifications of proteins by autoxidation products of carbohydrates, lipids, and amino acids: CML (derived from carbohydrates, lipids, and amino acid), pentosidine (derived from carbohydrates), MDA-lysine (derived from lipids), 4-hydroxynonenal-protein adduct (derived from lipids), and acrolein-protein adduct (derived from lipids and amino acid). All of the protein adducts were identified in expanded mesangial matrix and nodular lesions in DN. In IgA nephropathy, another primary glomerular disease leading to end-stage renal failure, despite positive staining for MDA-lysine and 4-hydroxynonenal-protein adduct in the expanded mesangial area, CML, pentosidine, and acrolein-protein adduct immunoreactivities were only faint in glomeruli. These data suggest a broad derangement in nonenzymatic biochemistry in diabetic glomerular lesions, and implicate an increased local oxidative stress and carbonyl modification of proteins in diabetic glomerular tissue damage (“carbonyl stress”).
Angiotensin-Converting Enzyme Inhibition and AT1 Receptor Blockade Modify the Pressure-Natriuresis Relationship by Additive Mechanisms in Rats with Human Renin and Angiotensinogen Genes
Authors: MERVAALA EERO , DEHMEL BASTIAN , GROSS VOLKMAR , LIPPOLDT ANDREA , BOHLENDER JÜRGEN , MILIA ANNA FRANCA , GANTEN DETLEV , LUFT FRIEDRICH C. 
Published: April 2021

Abstract.
The intrarenal factors responsible for hypertension in double-transgenic rats (dTGR) harboring human renin and human angiotensinogen genes are unclear. The pressure-natriuresis and -diuresis relationships in response to chronic angiotensin-converting enzyme (ACE) inhibition and AT1 receptor blockade were evaluated. Renal renin-angiotensin and nitric oxide (NO) system gene expression was also investigated. Six-week-old dTGR were treated for 3 wk with submaximal doses of cilazapril (10 mg/kg, orally) or losartan (10 mg/kg, orally) or with the drug combination. In untreated dTGR, pressure-natriuresis relationships were maximally shifted rightward by approximately 70 to 80 mmHg, and both renal blood flow (RBF) and GFR were markedly decreased. Submaximal cilazapril and losartan dosages both decreased systolic BP by 30 mmHg and shifted the pressure-natriuresis curves leftward by 25 to 30 mmHg. Cilazapril increased RBF and GFR to values observed in normotensive control animals but did not significantly affect fractional sodium excretion (FENa) or fractional water excretion (FEH2O) curves. In contrast, losartan had no significant effect on RBF or GFR but shifted the FENa and FEH2O curves leftward. The cilazapril and losartan combination completely normalized BP and shifted the pressure-natriuresis curves leftward more than did either drug alone. When cilazapril and losartan were administered at higher doses (30 mg/kg, orally), the two drugs equally shifted the pressure-natriuresis curves leftward, by 50 mmHg. Both drugs increased RBF and GFR; however, only losartan shifted FENa and FEH2O curves leftward. Human and rat renin and angiotensinogen genes were downregulated in dTGR and were increased by losartan and cilazapril treatments, whereas no changes in the expression of rat ACE and AT1A receptor genes were observed. Endothelial NO synthase expression was increased by cilazapril but not by losartan. Neither inducible NO synthase nor neural NO synthase gene expression was affected by drug treatments. Therefore, submaximal ACE inhibition enhanced sodium excretion mainly by increasing RBF and GFR, whereas submaximal AT1 receptor blockade decreased tubular sodium and water reabsorption. The combination of the two drugs produced an additive effect. The ACE inhibitor effects may involve increased endothelial NO synthase expression, perhaps related to the inhibition of bradykinin degradation.
Peritoneal Transport Properties and Dialysis Dose Affect Growth and Nutritional Status in Children on Chronic Peritoneal Dialysis
Authors: SCHAEFER FRANZ , KLAUS GÜNTER , MEHLS OTTO 
Published: April 2021

Abstract.
To evaluate a possible effect of peritoneal transport properties and dialysis dose on the physical development of children on chronic peritoneal dialysis, a cohort of 51 children was prospectively followed for 18 mo. Peritoneal transport characteristics were assessed by serial peritoneal equilibration tests (PET), dialysis efficacy by dialysate and residual renal clearance measurements, and growth and nutritional status by the longitudinal changes (Δ) of height SD score (SDS), body mass index (BMI) SDS, and serum albumin. Δ height SDS was negatively correlated with the creatinine equilibration rate observed in the initial PET (r = -0.31, P < 0.05). Multiple regression analysis confirmed the negative effect of the high transporter state (partial r
2 = 0.07), and disclosed an additional positive effect of dialytic CCr (partial r
2 = 0.11) and a weak negative effect of daily dialysate volume (partial r
2 = 0.04) on Δ height SDS. Δ BMI SDS was strongly age-dependent (r = -0.48, P < 0.001); while relative body mass gradually increased below 4 yr of age, it remained stable in older children. Positive changes in BMI SDS were associated with rapid PET creatinine equilibration rates (univariate r = 0.35, P < 0.05) and/or large dialysate volumes (multivariate partial r
2 = 0.11), suggesting a role of dialytic glucose uptake in the development of obesity. The change in serum albumin concentrations was positively correlated with dialysate volume (partial r
2 = 0.14), and negatively affected by dialytic protein losses (partial r
2 = 0.06). In conclusion, the peritoneal transporter state is a weak but significant determinant of growth and body mass gain in children on chronic peritoneal dialysis. Rapid small solute equilibration contributes to impaired growth but enhanced acquisition of body mass. Dialytic small solute clearance has a weak positive effect on statural growth independent of the transporter state, but does not affect body mass gain.
The Relationship of Untreated Borderline Infiltrates by the Banff Criteria to Acute Rejection in Renal Allograft Biopsies
Authors: MEEHAN SHANE M. , SIEGEL CHRISTOPHER T. , ARONSON ANDREW J. , BARTOSH SHARON M. , THISTLETHWAITE J. RICHARD , WOODLE E. STEVE , HAAS MARK 
Published: April 2021

Abstract.
The relationship of borderline infiltrates to acute rejection by Banff criteria in renal allografts of patients receiving only maintenance immunosuppression is not clear. Renal allograft biopsies with borderline lesions that were not treated with additional anti-rejection therapy were retrospectively studied. Sixty-five such biopsies were identified from 50 patients, and their outcome was determined by serum creatinine and/or histologic findings in subsequent biopsies, up to 40 d after the initial biopsy. In addition to the borderline infiltrates, there was evidence of acute cyclosporine or tacrolimus toxicity (58%), acute tubular necrosis (12%), and urinary obstruction (12%). Forty-day follow-up after 30 (46%) biopsies revealed serum creatinine <110% of baseline, and repeat biopsies were not indicated. In 17 (26%), the serum creatinine initially decreased, then increased, and follow-up biopsies showed acute rejection in nine. In 18 (28%), the creatinine remained elevated and follow-up biopsies revealed acute rejection in nine. The untreated borderline infiltrates were thus nonprogressive after 47 biopsies (72%) and progressed to histologic acute rejection after 18 (28%). When there was increasing or persistently elevated creatinine after the initial biopsy, 51% of cases (18 of 35) progressed to acute rejection. Infiltrates that progressed to rejection had more frequent glomerulitis (7 of 18 versus 3 of 47, P = 0.003) and Banff acute score indices (i+t+v+g) >2 (16 of 18 versus 29 of 47, P = 0.03). A majority (72%) of borderline infiltrates not given additional anti-rejection therapy did not progress to acute rejection over 40 d of follow-up, suggesting that conservative management of these lesions, at least in the short term, may be more appropriate than routine treatment as acute rejection.
Effect of Luminal Atrial Natriuretic Peptide on Chloride Reabsorption in Mouse Cortical Thick Ascending Limb
Authors: BAILLY CLAIRE 
Published: April 2021

Abstract.
Insofar as neutral endopeptidase inhibition has afforded evidence for a tubular luminal action of atrial natriuretic peptide (ANP), the present study was undertaken to investigate a possible effect of the peptide on chloride reabsorption (JCl) in thick ascending limb (TAL). Luminal addition of ANP to in vitro microperfused cortical TAL (CTAL) significantly decreased JCl with a threshold and a maximum concentration of 10-12 M and 10-9 M, respectively. A similar effect of 10-9 M ANP was observed in medullary TAL (MTAL). The effect of luminal ANP was significantly reduced by HS-142-1, a specific inhibitor of guanylyl cyclase receptor, and by H-8, a protein kinase G inhibitor, but was not affected by the protein kinase C inhibitor bisindolylmaleimide I. Unexpectedly, the effect of ANP was not additive with that of endothelin (ET), a peptide that was previously shown to decrease JCl in TAL through a calcium-independent, protein kinase C—mediated pathway. Indeed, ET-1 (10-8 M in the lumen) significantly decreased JCl and prevented a further effect of ANP on the same tubule. Similarly, the decrease of JCl induced by simultaneous addition of ET and ANP was not higher than that obtained with each agent alone. Conversely, the inhibitory effect of ANP was enhanced in the presence of cyclic guanosine monophosphate (cGMP; 10-6 M in the lumen). ET-1 significantly attenuated the ANP-stimulated generation of cGMP in microdissected CTAL and failed to prevent a further decrease of JCl promoted by a permeant cGMP analogue. It is concluded that luminal ANP decreased Cl reabsorption in mouse CTAL and MTAL. This effect was abrogated by ET-1 as a result of the inhibition of ANP-stimulated cGMP generation.
Expression of LOX-1, an Oxidized Low-Density Lipoprotein Receptor, in Experimental Hypertensive Glomerulosclerosis
Authors: NAGASE MIKI , KANAME SHINYA , NAGASE TAKASHI , WANG GANG , ANDO KATSUYUKI , SAWAMURA TATSUYA , FUJITA TOSHIRO 
Published: April 2021

Abstract.
Oxidized low-density lipoprotein (OxLDL) has been implicated in atherosclerosis and glomerulosclerosis. LOX-1 is a recently identified OxLDL receptor that is abundantly expressed in vascular endothelial cells. The aim of the present study was to investigate LOX-1 expression in the kidneys of hypertensive rats. Dahl salt-sensitive (DS) and salt-resistant (DR) rats were fed a 0.3% or 8% NaCl diet. Some DS 8% rats were treated with manidipine or hydralazine. LOX-1 gene expression was markedly elevated in the kidneys and glomeruli of hypertensive DS 8% rats compared with those of normotensive DR and DS 0.3% rats. Prolonged salt loading further increased the renal LOX-1 expression in DS rats. The LOX-1 upregulation in DS 8% rats was accompanied by renal overexpression of transforming growth factor-β1 and type I collagen, impaired renal function, and histologic glomerulosclerotic changes, all of which were ameliorated by antihypertensive treatment. LOX-1 was indeed expressed in the glomeruli in vivo and in cultured glomerular cells in vitro. However, LOX-1 expression was elevated in the aorta but not the kidneys of spontaneously hypertensive rats, which exhibited hypertension but minor glomerulosclerotic changes. In conclusion, the LOX-1 upregulation in the kidney of DS 8% rats was parallel to glomerulosclerotic changes and renal dysfunction, suggesting a possible pathogenetic role for renal LOX-1 in the progression to hypertensive glomerulosclerosis.
Differential Expression of Individual UT-A Urea Transporter Isoforms in Rat Kidney
Authors: BAGNASCO SERENA M. , PENG TAO , NAKAYAMA YUSHI , SANDS JEFF M. 
Published: April 2021

Abstract.
The rat renal urea transporter UT-A includes four mRNA isoforms: UT-A1, UT-A2, UT-A3, and UT-A4. This study detected by rapid amplification of cDNA ends (RACE), primer extension, and ribonuclease protection assay (RPA) a single transcription start site for UT-A1, UT-A3, and UT-A4, distinct from the one for UT-A2 and identified by 3′-RACE new transcripts of UT-A1, UT-A2, and UT-A3, characterized by alternative 3′ untranslated sequences (UTR). Expression of an alternative 3′UTR resulted in UT-A1 and UT-A2 transcripts that are approximately 400 bp shorter than the original cDNA. These mRNA isoforms (UT-A1b and UT-A2b) were present in low abundance in the inner medulla. Expression of an alternative 3′UTR for UT-A3 resulted in a 3.5 kb transcript (UT-A3b), which is 1.5 kb longer than the original UT-A3 cDNA. UT-A3b mRNA was easily detected by Northern hybridization in the inner medulla. This study examined whether different states of hydration induce homogeneous changes in mRNA expression of individual UT-A isoforms in the kidney. Analysis of UT-A1, UT-A1b, UT-A2, UT-A2b, UT-A3, and UT-A3b mRNA expression in rat kidney revealed that water deprivation markedly increases the relative abundance of UT-A2, UT-A2b, UT-A3, and UT-A3b mRNA in renal inner medulla, whereas UT-A1 and UT-A1b remain almost unchanged. The conclusion is that differential expression of individual UT-A mRNA isoforms occurs in the kidney and probably involves multiple regulatory mechanisms.
Polymorphism of Angiotensin Converting Enzyme, Angiotensinogen, and Angiotensin II Type 1 Receptor Genes and End-Stage Renal Failure in IgA Nephropathy
Authors: FRIMAT LUC , PHILIPPE CHRISTOPHE , MAGHAKIAN MARIE-NOE[Combining Diaeresis]LLE , JONVEAUX PHILIPPE , DE LIGNY BRUNO HURAULT , GUILLEMIN FRANCIS , KESSLER MICHE[Combining Grave Accent]LE 
Published: April 2021

Abstract.
The impact of renin-angiotensin system (RAS) gene polymorphism on the prognosis of IgA nephropathy (IgAN) is still debated. A longitudinal study of renal prognosis in patients with IgAN was conducted to search retrospectively for a genotype-phenotype association between RAS polymorphisms and end-stage renal failure (ESRF). A classification based on serum creatinine (Scr) and 24-h proteinuria (24-P) measured at the time of renal biopsy was used to estimate the risk of ESRF in IgAN: stage 1 (Scr ≤ 150 μmol/L and 24-P < 1 g), stage 2 (Scr > 150 μmol/L and 24-P < 1 g or Scr ≤ 150 μmol/L and 24-P ≥ 1 g), stage 3 (Scr > 150 μmol/L and 24-P ≥ 1 g). Deletion/insertion polymorphism (D/I) of the angiotensin I converting enzyme gene, M235T polymorphism (T/M) of the angiotensinogen gene and A1166C polymorphism (C/A) of the angiotensin II type 1 receptor gene were determined in 274 Caucasian men with biopsy-proven IgAN (n = 86, 112, and 76 in stages 1, 2, and 3, respectively). Mean global follow-up was 6 ± 5 yr after renal biopsy. For stages 1, 2, and 3, ESRF developed in 7 (8.1%), 39 (34.8%), and 49 (64.4%) cases (P < 0.0001), 11.7 ± 4, 5.4 ± 4, and 2 ± 2 yr, respectively, after renal biopsy (P < 0.001). The distributions of the three genotypes into the three stages were similar. Different distributions were observed when patients were grouped by stage and genotype: ID+DD: 72% in stage 1 versus 84.6% in stages 2 + 3 (P = 0.02; κ = 0.14); MT+TT: 66.2% in stages 1 + 2 versus 78.9% in stage 3 (P = 0.04; κ = 0.09); and AA+AC: 89.9% in stages 1 + 2 versus 97.4% in stage 3 (P = 0.04; κ = -0.1). However, with the use of the Cox proportional hazard model, none of the three genotypes was found to have predictive value for renal survival. Compared with Scr and 24-P, genotypes DD, TT, and AA are unlikely to serve as clinically useful predictors of ESRF in IgAN.