bluuebunny/crossref_metadata_2025_split huggingface dataset:
Hypocomplementemia Discloses Genetic Predisposition to Hemolytic Uremic Syndrome and Thrombotic Thrombocytopenic Purpura
Authors: NORIS MARINA , RUGGENENTI PIERO , PERNA ANNALISA , ORISIO SILVIA , CAPRIOLI JESSICA , SKERKA CHRISTINE , VASILE BEATRICE , ZIPFEL PETER F. , REMUZZI GIUSEPPE 
Published: May 2021

Abstract.
Familial hemolytic uremic syndrome (HUS) and thrombotic thrombocytopenic purpura (TTP) carry a very poor outcome and have been reported in association with decreased serum levels of the third complement component (C3). Uncontrolled consumption in the microcirculation, possibly related to genetically determined deficiency in factor H—a modulator of the alternative pathway of complement activation—may account for decreased C3 serum levels even during disease remission and may predispose to intravascular thrombosis. In a case-control study by multivariate analysis, we correlated putative predisposing conditions, including low C3 serum levels, with history of disease in 15 cases reporting one or more episodes of familial HUS and TTP, in 25 age- and gender-matched healthy controls and in 63 case-relatives and 56 control-relatives, respectively. The relationship between history of disease, low C3, and factor H abnormalities was investigated in all affected families and in 17 controls. Seventy-three percent of cases compared with 16% of controls (P < 0.001), and 24% of case-relatives compared with 5% of control-relatives (P = 0.005) had decreased C3 serum levels. At multivariate analysis, C3 serum level was the only parameter associated with the disease within affected families (P = 0.02) and in the overall study population (P = 0.01). Thus, subjects with decreased C3 serum levels had a relative risk of HUS or TTP of 16.56 (95% confidence interval [CI], 1.66 to 162.39) within families and of 27.77 (95% CI, 2.44 to 314.19) in the overall population, compared to subjects with normal serum levels. Factor H abnormalities were found in four of the cases, compared with three of the healthy family members (P = 0.02) and none of the controls (P = 0.04) and, within families, factor H abnormalities were correlated with C3 reduction (P < 0.05). Reduced C3 clusters in familial HUS and TTP is likely related to a genetically determined deficiency in factor H and may predispose to the disease. Its demonstration may help identify subjects at risk in affected families.
A Cholesteryl Ester Transfer Protein Gene Mutation and Vascular Disease in Dialysis Patients
Authors: KIMURA HIDEKI , GEJYO FUMITAKE , YAMAGUCHI TOMOKO , SUZUKI SATORU , IMURA TOSHIO , MIYAZAKI RYOICHI , ARAKAWA MASAAKI 
Published: May 2021

Abstract.
Among patients undergoing maintenance hemodialysis, a decreased high-density lipoprotein cholesterol (HDL-C) concentration is among the most common abnormalities of lipid metabolism and apparently is an independent risk factor for vascular disease. A common missense mutation of cholesteryl ester transfer protein gene, D442G (Asp 442 to Gly), increases HDL-C levels through the reduced activity of cholesteryl ester transfer from HDL to VLDL, but the mutation also may lead to reduced activity of reverse cholesterol transport. To investigate the effect of the D442G polymorphism on atherosclerotic complications in dialysis patients, the genotype and allele frequency of the polymorphism were determined in 414 unselected dialysis patients and 220 control subjects, and postprandial serum lipid levels were measured in the dialysis patients. A similar genotype distribution was found between hemodialysis patients and healthy control subjects, and in dialysis patients with and without vascular disease. Serum levels of total cholesterol and HDL-C did not differ between patients with and without the mutation and in patients with and without vascular disease. However, patients with sub-median HDL-C levels (<45 mg/dl) had an independent odds ratio of 1.8 for vascular disease (95% confidence interval, 1.04 to 3.2; P < 0.05). In this low-HDL-C subgroup, patients with the D442G mutation had a significantly higher prevalence of vascular disease than those with no mutation (54.5% versus 24.4%; P < 0.05), and an independent odds ratio of 4.9 (95% confidence interval, 1.05 to 22.65; P < 0.05). In conclusion, the D442G mutation is an independent risk factor for atherosclerotic complications in dialysis patients with HDL-C levels below 45 mg/dl.
Pathophysiology of Edema Formation in Children with Nephrotic Syndrome Not Due to Minimal Change Disease
Authors: VANDE WALLE JOHAN G. J. , DONCKERWOLCKE RAYMOND A. , KOOMANS HEIN A. 
Published: May 2021

Abstract.
It has been shown that children with nephrotic syndrome due to minimal change disease (MCD) can present with avid salt retention and stimulated vasoactive hormones, as well as with stable edema. The present study examines these conditions in children with nephrotic syndrome not due to MCD (non-MCD). In six children with hypovolemic symptoms (congenital nephrotic syndrome in four), strong sodium retention (fractional sodium excretion, FENa, 0.2 ± 0.2%) was found. Lithium clearance (FELi) and maximal water excretion (V
max) were suppressed, suggesting avid sodium reabsorption throughout the nephron. Aldosterone, renin, and norepinephrine were elevated. Sixteen other children with non-MCD had stable edema. FENa was 1.8 ± 1.1%, whereas FELi, V
max, and hormones were normal, and not different from data in 35 nonproteinuric children. In children with MCD, 12 presented with hypovolemic symptoms and strong sodium retention (FENa 0.3 ± 0.3%), whereas 15 were stable (FENa 1.1 ± 0.7%). Regarding tubular sodium handling and hormones, the same distinction could be made as for the children with non-MCD. However, hypoproteinemia differed. In the children with non-MCD lesions, plasma colloid osmotic pressure was significantly lower in the hypovolemic types (4.2 ± 0.4 mmHg) than in those with stable edema (13.0 ± 3.8 mmHg; P < 0.05); in MCD, no such difference existed (respectively, 8.1 ± 3.0 and 9.9 ± 2.2 mmHg). In summary, children with nephrotic syndrome may present with pathophysiologic pictures of decreased effective circulating volume or of stable edema, regardless of whether they have non-MCD or MCD. The pathogenesis of the hypovolemic picture seems to be different, since it is associated with extreme hypoproteinemia only in the children with non-MCD.
The Peritoneal Membrane in Peritoneal Dialysis Patients
Authors: CHAGNAC AVRY , HERSKOVITZ PEARL , WEINSTEIN TALIA , ELYASHIV SIMCHA , HIRSH JUDITH , HAMMEL ILAN , GAFTER UZI 
Published: May 2021

Abstract.
The surface area of the peritoneal membrane in contact with dialysate is an important determinant of solute transport across the peritoneum. Yet there is no method for its estimation in peritoneal dialysis patients. In this study, stereologic methods were applied to computerized tomography (CT) imaging of the peritoneal membrane to estimate the peritoneal membrane surface area. The method was first validated by implementing stereologic methods on a phantom of known surface area. The phantom was a distorted bottle filled with contrast media. Series of thin helical CT sections were performed, and random sections were obtained after reconstruction. A transparent counting grid was placed over the random sections. The surface area was estimated using 9, 18, and 36 random sections. To calculate the coefficient of variation (CV) of the method, 20 different combinations of 9, 18, and 36 random sections were used. With 36 random sections, the error in estimation of the bottle's surface area was - 9.4% to + 8.8%. The CV was 5.0%. Decreasing the number of sections used to 18 and 9 yielded a CV of 7.8 and 12.3%, respectively. This method was then applied to the peritoneal membrane, which was visualized by instilling dialysate containing contrast media into the peritoneal cavity of peritoneal dialysis patients. The estimated peritoneal membrane surface area of six patients was 0.55 ± 0.04 m2. This novel method permits the measurement of the peritoneal membrane surface area with a high degree of accuracy.
Mortality in End-Stage Renal Disease
Authors: VONESH EDWARD F. , MORAN JOHN 
Published: May 2021

Abstract.
Recent registry studies comparing mortality between peritoneal dialysis (PD) and hemodialysis (HD) patients show conflicting results. The purpose of this study is to determine whether previously published results showing higher mortality for patients treated with PD versus HD in the United States continue to hold true over the period 1987-1993. National mortality rates for PD and HD were extracted from the U.S. Renal Data System (USRDS) annual reports for the cohort periods: 1987-1989, 1988-1990, 1989-1991, 1990-1992, and 1991-1993. Using Poisson regression, death rates per 100 patient years were compared between PD and HD for each cohort period controlling for age, gender, race, and cause of end-stage renal disease (diabetes versus nondiabetes). When incident patients and patients with a prior transplant were included in the analysis, starting with the 1989-1991 cohort, we found little or no difference in the relative risk (RR PD:HD) of death between PD and HD (1987-1989: RR = 1.17, P < 0.001; 1988-1990: RR = 1.12, P < 0.001; 1989-1991: RR = 1.06, P = NS; 1990-1992: RR = 1.06, P = NS; 1991-1993: RR = 1.08, P = 0.043). After a test for goodness-of-fit, separate analyses for diabetic patients and nondiabetic patients were done to examine unexplained variation in death rates. For nondiabetic patients, there was less than a 1% difference in the adjusted 1-yr survival between PD and HD from 1989-1993 (1989-1991: RR = 1.05, P = NS; 1990-1992: RR = 1.04, P = NS; 1991-1993: RR = 1.07, P < 0.01). Among diabetic patients, the PD:HD death rate ratio varied significantly according to gender and age. For the average male diabetic patient, there was little or no difference in risk between PD and HD from 1989-1993 (1989-1991: RR = 1.02, P = NS; 1990-1992: RR = 1.05, P = NS; 1991-1993: RR = 1.08, P < 0.01). For diabetic patients under the age of 50, those treated with PD had a significantly lower risk of death than those treated with HD (1989-1993: 0.84 ≤ RR ≤ 0.89, P < 0.005). Over the same period, female diabetic patients treated with PD had a higher risk, on average, than HD (1.18 ≤ RR ≤ 1.19, P < 0.001) as did diabetic patients over the age 50 (1.28 ≤ RR ≤ 1.30, P < 0.001). Unlike previously published results that were restricted to prevalent-only patients, this national study of both prevalent and incident patients found little or no difference in overall mortality between PD and HD. The recent trends in mortality likely reflect the inclusion of incident patients, but they may also reflect changes in case-mix differences and/or improved PD practice. Additional incident-based studies that allow for additional case-mix adjustments are needed to better compare outcomes between HD and PD.
The ETA Receptor Blocker LU 135252 Prevents Chronic Transplant Nephropathy in the “Fisher to Lewis” Model
Authors: ORTH STEPHAN R. , ODONI GIULIO , AMANN KERSTIN , STRZELCZYK PIOTR , RASCHACK MANFRED , RITZ EBERHARD 
Published: May 2021

Abstract.
The effect of the orally highly bioavailable and specific endothelin A (ETA) receptor antagonist LU 135252 was assessed in a model of chronic renal allograft nephropathy. Kidneys of Fisher rats were orthotopically grafted to Lewis rats. Fisher autografts and kidneys after uninephrectomy served as controls. All animals received low-dose cyclosporin A (CsA; 1.5 mg/kg body wt) for 10 d after surgery. Allotransplanted animals were then randomized to receive standard diet or a diet designed to deliver 30 mg of LU 135252/kg body wt per d for 35 wk. BP was monitored telemetrically. Treatment with LU 135252 did not affect systolic or diastolic pressure. Indices of glomerulosclerosis (GSI), and tubulointerstitial and vascular damage were measured. Chronic transplant nephropathy was almost completely prevented by LU 135252 compared with untreated allografts or kidneys of uninephrectomized controls, i.e., GSI 0.7 ± 0.12 versus 1.6 ± 0.25 (P < 0.001) versus 0.7 ± 0.06 (P < 0.001). Allograft weight and serum creatinine were significantly lower in treated versus untreated animals. The results are consistent with the notion that ETA receptor-mediated events play a role in the genesis of chronic transplant nephropathy.
Influence of Donor Factors on Early Function of Graft Kidneys
Authors: SURI DEEPIKA , MEYER TIMOTHY W. 
Published: May 2021

Abstract.
Factors which influence graft function can be divided into donor factors that affect both kidneys from the same donor equally and postdonor factors that affect each kidney individually. This study assessed the influence of donor factors on graft function early after transplantation. Sixty-one donors who provided kidneys that were transplanted locally into two separate recipients were identified. Recipient creatinine clearance values were estimated from serum creatinine concentrations using a computer model. Pairwise ANOVA showed that donor factors accounted for 35 to 45% of the variation in recipient creatinine clearance from 2 d to 2 wk posttransplantation. Although donor factors had a large aggregate effect during this period, individual factors that influenced graft function could not be identified from analysis of donor medical records. At 6 mo after transplantation, the effect of donor factors on graft function was no longer discernible. These results show that the condition of the donor exerts an important influence on graft function early after transplantation. More detailed study is required to identify individual factors that contribute to this effect.
Effect of Danaparoid Sodium on Proteinuria, von Willebrand Factor, and Hard Exudates in Patients with Diabetes Mellitus Type 2
Authors: VAN DER PIJL JOHAN W. , LEMKES HERMAN H. P. J. , FRÖLICH MARIJKE , VAN DER WOUDE FOKKO J. , VAN DER MEER FELIX J. M. , VAN ES LEENDERT A. 
Published: May 2021

Abstract.
In diabetic nephropathy, heparan sulfate glycosaminoglycan side chains are reduced in glomerular basement membranes proportionally to the degree of proteinuria. Recently, it was demonstrated that additional therapy with danaparoid sodium, a mixture of sulfated glycosaminoglycans with mainly heparan sulfate, lowered proteinuria in type 1 diabetes patients with diabetic nephropathy. A randomized placebo-controlled parallel study was performed with 750 anti-Xa units of danaparoid sodium once daily in type 2 diabetes patients with severe proteinuria. The aim of the study was to evaluate the possible effects of danaparoid sodium on proteinuria, endothelial dysfunction, and hard exudates in the retina and to determine the safety/tolerability of this drug. Twenty-two patients completed the study, and one patient had to stop prematurely after 6 wk of danaparoid sodium treatment because of urticaria at the injection sites. Apart from a small decrease of hemoglobin and minor skin hematomas at the injection site in five patients in the danaparoid sodium group, no other safety parameters showed any clinically or statistically significant difference between and within groups. The relative change in time of both the urinary albumin and protein excretion rate corrected for creatinine did not differ between both treatment arms (P = 0.2 and 0.49, respectively). No retinal complications or changes of hard exudates occurred. von Willebrand factor was elevated in both groups, but was not influenced by either treatment modality. Contrary to the beneficial effects that occurred in type 1 diabetes patients with diabetic nephropathy, treatment for 8 wk with 750 anti-Xa units of danaparoid sodium gave no reduction of proteinuria, hard exudates, and von Willebrand factor.
Transmembrane Proteins in the Tight Junction Barrier
Authors: FANNING ALAN S. , MITIC LAURA L. , ANDERSON JAMES MELVIN 
Published: May 2021

Abstract.
Three types of transmembrane proteins have been identified within the tight junction, but it remains to be determined how they provide the molecular basis for regulating the paracellular permeability for water, solutes, and immune cells. Several of these proteins localize specifically within the continuous cell-to-cell contacts of the tight junction. One of these, occludin, is a cell adhesion molecule that has been demonstrated to influence ion and solute permeability. The claudins are a family of four-membrane spanning proteins; unexpectedly, other members of this family have already been characterized without recognizing their relationship to tight junctions. Junction adhesion molecule, the most recently identified tight junction component, is a member of the Ig superfamily and influences the paracellular transmigration of immune cells. A plaque of cytoplasmic proteins under the junction may be responsible for scaffolding the transmembrane proteins, creating a link to the perijunctional actin cytoskeleton and transducing regulatory signals that control the paracellular barrier.
Gentamicin Inhibits Renal Protein and Phospholipid Metabolism in Rats
Authors: SUNDIN DAVID P. , SANDOVAL RUBEN , MOLITORIS BRUCE A. 
Published: May 2021

Abstract.
Studies were undertaken to characterize the mechanism of aminoglycoside-induced nephrotoxicity. Early time points in gentamicin treatment (1 to 3 d) were used to investigate the development of toxic events without the complication of gross morphologic cellular alterations. Enzyme activities of cortical homogenates and brush border membrane (BBM) preparations documented little effect on specific activities or the ability to isolate representative membrane fractions. In vivo protein synthesis experiments demonstrated that gentamicin reduced cellular protein synthesis after 2 d of treatment. This inhibition increased to 50% on the third day. Total cellular proteins synthesis was inhibited to the same extent as BBM protein synthesis. However, gentamicin had different effects on homogenate versus BBM phospholipids. The total phospholipid contents in cortical homogenates and BBM from treated animals were increased, compared with control animals. A significant decrease in phospholipid synthesis was observed only in homogenates from treated animals. When effects on individual phospholipids were investigated, only an increase in phosphatidylinositol levels was observed in cortical homogenates from treated rats. However, gentamicin treatment was demonstrated to increase the levels of phosphatidylinositol and phosphatidylcholine, while decreasing the level of sphingomyelin (SPH), in BBM. Incorporation of 32P into SPH, phosphatidylserine, and phosphatidylethanolamine was inhibited in cortical homogenates from gentamicin-treated animals; among BBM phospholipids, however, a significant decrease was observed only for SPH synthesis. It was concluded that inhibition of phospholipid degradation was quantitatively the major contributor to the effects of gentamicin on phospholipid metabolism. Confocal microscopic studies, using tracer amounts of fluorescently labeled gentamicin, revealed gentamicin in large, mostly basal structures. Correlative electron microscopic studies, using photo-oxidation techniques, demonstrated that these structures consisted of lysosomal, Golgi complex, and mitochondrial structures. These observations suggest retrograde trafficking of gentamicin and indicate a general mechanism of gentamicin-induced nephrotoxicity.
Silica Exposure in Anti-Neutrophil Cytoplasmic Autoantibody-Associated Glomerulonephritis and Lupus Nephritis
Authors: HOGAN SUSAN L. , SATTERLY KAREN K. , DOOLEY MARY ANNE , NACHMAN PATRICK H. , JENNETTE J. CHARLES , FALK RONALD J. 
Published: May 2021

Abstract.
Anti-neutrophil cytoplasmic autoantibody (ANCA)-associated small-vessel vasculitis (SVV) and systemic lupus erythematosus (SLE) are rare diseases with unknown causes. Silica dust exposure has been suggested to be an environmental factor that may increase the risk of developing these and other autoimmune disorders. This is a report of two case-control studies to determine whether silica dust exposure is independently associated with ANCA-SVV with glomerulonephritis and SLE nephritis. Patients were screened through a collaborative network of 225 private practice and university nephrologists (the Glomerular Disease Collaborative Network). Patients with ANCA-SVV or SLE, all with biopsy-proven renal involvement, were included. Control subjects were patients without ANCA-SVV or SLE who had been referred to the same renal clinics and were matched for gender, race, and age (within 5 yr). Exposures to silica, exposures to other environmental agents, and smoking histories were evaluated using a self-administered questionnaire. Enrollment consisted of 65 patients with ANCA-SVV and 51 patients with SLE nephritis. Silica dust exposure was reported by 46% of patients with ANCA-SVV, compared with 20% of control subjects (P = 0.001). The odds ratio of silica dust exposure was 4.4 times greater for patients with ANCA-SVV, compared with control subjects (95% confidence interval, 1.36 to 13.4; P = 0.013). The odds ratios for silica dust exposure were similar for patients with ANCA-SVV with lung or sinus vasculitis (odds ratio, 4.5; 95% confidence interval, 0.99 to 20.83; P = 0.054) and those without lung or sinus vasculitis (odds ratio, 4.7; 95% confidence interval, 1.34 to 16.24; P = 0.016). Silica dust exposure was reported by 12% of patients with SLE nephritis, compared with 25% of control subjects (P = 0.047). The odds ratio for exposure to silica dust was not statistically different for patients with SLE nephritis, compared with control subjects (odds ratio, 0.001; 95% confidence interval, <0.01 to >100; P = 0.993). Activities and environments known to cause high levels of exposure to silica dust were associated with ANCA-SVV but not with SLE nephritis.
Impact of Sodium and Ultrafiltration Profiling on Hemodialysis-Related Symptoms
Authors: OLIVER MATTHEW J. , EDWARDS LLOYD J. , CHURCHILL DAVID N. 
Published: May 2021

Abstract.
Dialysate sodium and ultrafiltration profiling are two methods to reduce symptoms during hemodialysis. The objective of the study was to determine the efficacy of combining these techniques to reduce symptoms in chronic hemodialysis patients. Blood volume changes were measured to determine whether any benefit of profiling could be explained through this mechanism. Patients were randomized to profiled dialysate sodium and ultrafiltration or constant dialysate sodium and ultrafiltration. The study was a two-period, two-treatment, crossover design with repeated measures. The primary outcome was hypotension and/or symptomatic events observed by the dialysis nurse. Secondary outcomes were symptom survey scores, weights, BP, and blood volume changes. Thirty-three patients were randomized. On standard treatment, 30.6% of dialysis sessions were symptomatic compared with 20.4% on profiled treatments. The odds ratio for the development of hypotension or symptomatic event on profiled treatments was 0.61 (95% confidence interval, 0.39 to 0.96) compared with standard treatment. Patients had lower symptom scores by questionnaire in both the intradialytic and the interdialytic periods during profiled treatments. Predialysis weight was greater during profiled treatments by 0.3 kg (P = 0.008), but there were no differences in postdialysis weight, BP, or thirst. There was no difference in maximum decrease in blood volume during the two treatments (standard, -11.2%; profiled, -10.0%; P = 0.08), but there was a significant difference in the rate of change in blood volume (standard, -2.96%/h; profiled, -1.96%/h; P < 0.001). Decrease in blood volume, rate of change in blood volume, and predialysis weights were not associated with hypotension or symptomatic dialysis sessions. In conclusion, dialysate sodium and ultrafiltration profiling significantly reduces hemodialysis-related symptoms. Profiling reduces the slope of the blood volume curve during dialysis, but blood volume changes are not predictive of symptomatic events for an individual patient.