bluuebunny/crossref_metadata_2025 huggingface dataset:
Assessment of the Length of Each Hemodialysis Session by On-Line Dialysate Urea Monitoring
Authors: Hernandez-Herrera G. , Martin-Malo A. , Rodriguez M. , Aljama P.
Published: April 2003

Hemodialysis (HD) prescription is usually based on the periodical measurement of the Kt/V achieved in a midweek dialysis session. The purpose of the study was to assess the duration of each HD session to achieve a target dose of dialysis. This allowed to determine whether a given dialysis session may be considered representative of the other HD sessions. Seventy-two HD sessions were studied in 4 stable patients, who were randomly dialyzed during 3 consecutive periods, each lasting 2 weeks, using a different blood flow rate (Qb) in each period: 400, 300 or 200 ml/min. All HD were prolonged to achieve an on-line dialysate urea monitor (UM) Kt/V of 1.2. The UM Kt/V was compared with the Kt/V calculated using pre-HD, post-HD and rebound (45 min post-HD) plasma water urea concentrations. Comparison of the duration of the second midweek dialysis session with the length of the other HD showed 95% concordance intervals (±2 SD) of ±21.08 min for Qb 400, ±26.88 min for Qb 300 and ±37.02 min for Qb 200 ml/min. The 95% concordance intervals for whole body urea clearance were ±32.0, ±20.36 and ±15.62 ml/min for Qb 400, 300 and 200 ml/min, respectively. No differences were observed between UM Kt/V and blood-based double-pool Kt/V obtained by the second-generation Daugirdas (1.18 ± 0.08) and Garred (1.19 ± 0.08) Kt/V formulas. In conclusion, a great variability was observed between different HD sessions with regard to the whole body urea clearance and the time required to attain a target Kt/V even when the HD characteristics remained constant. The length of every HD required to achieve a target dose of dialysis can be assessed by on-line dialysate urea monitoring.
Cortical Na+,K+-ATPase Activity, Abundance and Distribution after in vivo Renal Ischemia without Reperfusion in Rats
Authors: Coux Gabriela , Trumper Laura , Elías M. Mónica
Published: April 2003

The aim of our work was to study the changes in activity, abundance and distribution of sodium, potassium-adenosine triphosphatase (Na+,K+-ATPase) in membranes of cortical tubular cells in an in vivo model of ischemic injury without reperfusion. Na+,K+-ATPase, alkaline phosphatase (AP) activities and their distribution in membranes isolated from renal cortex using a Percoll gradient were studied after different ischemic periods. Na+,K+-ATPase α-subunit protein abundance was analysed by Western-blot. Plasma urea and cortical adenosine 5’triphosphate (ATP) were also measured. In cortical homogenates 5 min of ischemia promoted a diminution in ATP content. Na+,K+-ATPase activity diminished after 40 min and AP after 100 min of ischemia. Na+,K+-ATPase activity in the Percoll gradient fractions after 5 min peaked at a higher density and was significantly decreased after 40 min. AP activity was decreased in typically enriched apical membranes after both times of ischemia. At each time studied Na+,K+-ATPase abundance was increased in cortical homogenates and membranes. Our results showed opposite effects of ischemia on Na+,K+-ATPase activity and abundance. Increased levels of Na+,K+-ATPase protein were observed. The enzyme would be rapidly delivered to membrane domains and become inactivated as ischemia persists.
Target Hemoglobin in Patients with Renal Failure
Authors: Eckardt K.-U.
Published: April 2003

15 years after recombinant erythropoietin (EPO) has become available for the treatment of renal anemia, the target hemoglobin concentration to be achieved is still controversial. A positive impact of partial correction of renal anemia on quality of life has been conclusively demonstrated. Several more recent studies indicate that further improvement of well-being can be achieved with normalization of hemoglobin levels. In addition, there is increasing evidence that anemia is associated with the progression of left-ventricular hypertrophy and mortality. These findings imply that correction of renal anemia has the potential to improve patient prognosis. However, in patients with advanced cardiac disease, the US normal hematocrit failed to demonstrate a prognostic benefit and instead suggested that the attempt to normalize hemoglobin may be harmful. Nevertheless, in patients with less advanced cardiac disease complete correction of renal anemia may prevent progressive ventricular dilatation. The impact of early anemia correction is currently tested in several trials in predialysis patients. Irrespective of the uncertainities about the upper target range, current US and European guidelines have defined a hemoglobin concentration of 11 g/dl as the lower target range on the basis of both symptomatic and prognostic considerations. In the majority of patients these minimum requirements are not yet achieved. Less then 10% of patients receive EPO prior to the onset of dialysis, the mean hemoglobin level at the start of dialysis is not higher than 9 g/dl and a significant proportion of patients permanently remain below 11 g/dl.
Persistence of Immunologic Memory in Long-Term Hemodialysis Patients and Healthcare Workers Given Hepatitis B Vaccine: Role of a Booster Dose on Antibody Response
Authors: Peces Ramón , Laurés Ana S.
Published: April 2003

Hepatitis B (HB) vaccine is effective in producing protection against HB virus infection, but the persistence of immunity remains largely unknown. Seventy-six hemodialysis (HD) patients (60 after primary HB vaccination and 16 with natural immunity) and 46 healthcare workers (32 after primary HB vaccination and 14 with natural immunity) were followed up for 10 years to evaluate the persistence of immunity. Ten years after vaccination, the analysis showed a lower seroconversion rate (38 vs. 75%, p < 0.001) in HD patients as compared with healthcare workers. In the follow-up period, the protective immunity developed through HB virus infection also showed a lower seroconversion rate (44 vs. 86%, p < 0.025) in HD patients as compared with healthcare workers. To assess the status of immunologic memory, we administered a booster dose of HB vaccine 3–12 years (mean 6.7 ± 0.6 years) after primary vaccination in a selected group of 37 HD patients who presented a decline of their antibodies or were nonresponders. In another group of 12 healthcare workers who had a decline of their antibodies, we also administered a booster dose of HB vaccine 5–8 years (mean 5.8 ± 0.3 years) after primary vaccination. Nineteen of the 37 HD patients (51%) presented an anamnestic response to the booster dose, and 15 of these (40%) were high responders. All of the healthcare workers responded to the booster dose with a high antibody response. We conclude that patients undergoing HD not only have lower rates of immunization to HB than healthy adults, but also that these are frequently transient. Booster doses after a primary course of vaccine are effective in about the half of HD patients who presented a decline of their antibodies or were nonresponders but whether they are necessary is unclear. The majority of healthcare workers continue to have high levels of protective HBs antibody for at least 10 years and routine boosters are not required.
Serum Levels of Advanced Glycosylation End Products in Diabetic Nephropathy
Authors: Kanauchi Masao , Nishioka Hisayuki , Dohi Kazuhiro
Published: April 2003

Background/Aims: Advanced glycosylation end products (AGEs) are important pathogenetic factors underlying diabetic complications. Recently, a highly reliable new enzyme-linked immunosorbent assay for these metabolites has been established. We used the assay to correlate AGEs in serum with renal function categories and histopathology in patients with diabetic nephropathy. Methods: Type 2 diabetic patients (n = 71) and healthy control subjects (n = 35) were studied. The diabetic subjects were divided into two groups: normal renal function and chronic renal failure not requiring dialysis. In renal biopsy specimens from 22 diabetic subjects with a normal renal function, the severity of glomerular lesions was assessed morphometrically in terms of the ratio of the area of periodic acid-Schiff stained mesangium to total glomerular area. Results: The serum AGE concentrations were higher in both undialyzed diabetic groups, especially in those with renal failure, than in the controls. The serum AGE concentrations increased with the severity of glomerular lesions (morphometric ratio under 15%, 2.85 ± 0.73 mU/ml; 15–24%, 4.01 ± 0.71 mU/ml; 25% or more, 5.12 ± 0.64 mU/ml). Conclusions: The serum AGE levels measured by the new enzyme-linked immunosorbent assay reflected the severity of glomerulopathy, and, therefore, it may be a clinically useful tool for assessing diabetic renal complications.
Differential Effects of FMLP-Activated Neutrophils from Patients with IgA Nephropathy Enhanced Endothelin 1 Production of Glomerular Mesangial Cells
Authors: Chen H.C. , Guh J.Y. , Chang J.M. , Lai Y.H.
Published: April 2003

Background: Neutrophil infiltration in the glomeruli is common in patients with IgA nephropathy (IgAN). The pathogenetic roles of the infiltrated neutrophils and their relationship with glomerular mesangial cells, however, are not clear. Methods: We examined the effects of coculture with N-formyl-methionyl-leucyl-phenylalanine (FMLP) activated neutrophils on the viability, endothelin 1 (ET-1) production, and ET-1 mRNA expression of rat glomerular mesangial cells. Neutrophils were isolated from 15 IgAN patients, from 13 patients with non-IgA mesangial proliferative glomerulonephritis (MsPGN), and from 10 normal controls. Results: The ET-1 production by mesangial cells was significantly higher after stimulation with FMLP-activated neutrophils from IgAN patients than that of MsPGN patients and normal controls, and this effect was significantly abolished by pretreating mesangial cells with superoxide dismutase and partly abolished by catalase. The ET-I mRNA expression of mesangial cells showed a parallel increase with ET-1 protein. The trypan blue exclusion test showed significant mesangial cell death after stimulation with FMLP-activated neutrophils as compared with quiescent neutrophils, and the cell death was also prevented by superoxide dismutase but not catalase. The FMLP-activated neutrophils from IgAN patients produced more superoxide than those of MsPGN patients and normal controls. Conclusion: The FMLP-activated neutrophils from patients with IgAN have differential effects in enhancing the cell death and the ET-1 production of glomerular mesangial cells through the release of superoxide.
Renal Involvement Induced by Human Parvovirus B19 Infection
Authors: Takeda Shin-ichi , Takaeda Chikako , Takazakura Eisuke , Haratake Joji
Published: April 2003

In an attempt to clarify the renal involvement induced by human parvovirus B19 (HPB19) infection, we investigated 6 adult patients with transient urinary abnormalities followed by erythema infectiosum. All patients had HPB19-specific IgM antibody and showed mild proteinuria of 0.2–1.2 g/day with or without microscopic hematuria. In 5 patients a decrease of complement was present, and in 2 the circulating immune complex levels were elevated. All patients showed mild or moderate endocapillary proliferation with leukocytic infiltrates in glomeruli and leukocytic infiltrates with edema around interlobular arteries and arterioles. Immunofluorescence microscopy revealed C3c deposits with immunoglobulins along the glomerular capillary walls and in the walls of small arteries and arterioles. Electron microscopic studies showed swelling of the endothelial cells and small electron-dense deposits in mesangium (in all 6 patients) and subendothelium (in 5 of 6 patients). However, HPB19 VP1 and VP2 capsid antigens were not demonstrated in the glomerulus or the vascular wall in any patient. These findings suggest that the renal lesions caused by an immune complex mediated phenomenon would be closely correlated with the HPB19 infection, although the precise mechanism is not entirely clear, and that in adults HPB19 should be thought of as a possible cause of acute postinfectious glomerulonephritis.
Vitamin E Inhibits Proliferation of Primary Cultured Human Mesangial and Endothelial Cells
Authors: Zhang Yixiang , Yasumoto Yuichiro , Mei Changlin , Arima Terukatsu
Published: April 2003

Background: Vitamin E (VE) has been used as an antioxidant and has been suggested to inhibit the proliferation of mesangial cells in rat and vascular endothelial cells. The direct effect of VE on primary cultures of mesangial cells (MC) and endothelial cells (EC) from the human glomerulus was studied. Methods: (1) MC (in 17 or 2.5% FCS DMEM) or EC (in 10 or 5% FCS CSC) at 5,000 cells/well was incubated with serial concentrations of VE from 0.05 to 50 µg/ml (0.06 to 60 IU/l). (2) MC was cocultured with 160, 80, 40 or 20 µg/ml of low-density lipoprotein (LDL) or oxidized LDL (ox-LDL) in 17 or 2.5% FCS DMEM with or without VE. After 3 days of incubation at 37°C in 5% CO2, cell proliferation was measured by the Premix WST-1 Assay System. Results: The concentration of VE that significantly inhibited the proliferation of MC cultured in 17 or 2.5% FCS DMEM was 50 or 2.5 µg/ml (60 or 3.0 IU/l), respectively, and that of EC in 10 or 5% FCS medium was 50 or 25 µg/ml (60 or 30 IU/l). VE at 25 µg/ml (30 IU/l) inhibited the LDL proliferative effect on MC cultured in 2.5 FCS DMEM by 21.79–93.21% in a LDL concentration-dependent manner. There was little difference between the effects of LDL and ox-LDL on the VE inhibitory effect on MC under our experimental conditions. Conclusion: VE at low concentrations had no effect on the proliferation of both MC and EC, but at high concentrations, it showed an inhibitory effect on both cells.
Steroid Pulse Therapy Combined with Tonsillectomy in IgA Nephropathy Associated with Diabetes mellitus
Authors: Furuta Takashi , Hotta Osamu , Horigome Ikuo , Chiba Shigemi , Noshiro Hiroo , Miyazaki Mariko , Satoh Mitsuhiro , Honda Satoko , Taguma Yoshio
Published: April 2003

Ten patients with biopsy-confirmed IgA nephropathy associated with diabetes mellitus underwent dietary weight control and three courses of intravenous pulses of methylprenisolone followed by prednisolone for 6–12 months and tonsillectomy. The average length of the follow-up period was 47.8 (range 30–96) months. As compared with pretreatment values, hematuria, proteinuria, body mass index, and hemoglobin A1c were significantly improved after treatment. There were no significant differences with regard to blood pressure and glycemic blood glucose control. There was no worsening of diabetic retinopathy and nephropathy. During steroid pulse therapy, the patients who were treated with insulin needed a higher dosage of insulin; after steroid pulse therapy, the dosage returned to baseline. Even patients with IgA nephropathy and diabetes mellitus could be treated with combined therapy and showed beneficial responses, it they succeeded in reducing body mass index.
Neuraminidase Treatment Abrogates the Binding Abnormality of IgA1 from IgA Nephropathy Patients and the Differential Charge Distribution of Its α-Heavy Chains
Authors: Hashim O.H. , Shuib A.S. , Chua C.T.
Published: April 2003

We have studied the interaction of the Gal-GalNAc-reactive champedak lectin-C with neuraminidase-treated and untreated IgA1 from IgA nephropathy patients. The binding ability of the lectin to untreated IgA1 from IgA nephropathy patients was significantly lower as compared to the untreated IgA1 from normal controls. This differential lectin-binding capacity was abrogated when the experiment was performed on neuraminidase-treated sera. Treatment of the serum IgA1 with neuraminidase also abrogated the differential charge distribution between the α-heavy chains of IgA nephropathy patients and normal controls.
Role of Ginsenoside-Rd in Cisplatin-Induced Renal Injury: Special Reference to DNA Fragmentation
Authors: Yokozawa Takako , Dong Erbo
Published: April 2003

DNA of LLC-PK1 cells cultured with cisplatin was fragmented to produce low-molecular-weight structures. Agarose gel electrophoresis of the DNA revealed a ladder pattern characteristic of apoptosis, indicating the induction of apoptosis by cisplatin. However, the degree of apoptosis was lower in cells cultured with cisplatin in the presence of ginsenoside-Rd, and this was accompanied by suppressed leakage of lactic dehydrogenase into the culture medium. The ladder pattern was detected on electrophoresis of DNA in renal tissue samples obtained from rats given an intravenous injection of cisplatin. Such DNA fragmentation was less conspicuous in rats given ginsenoside-Rd orally for 30 days prior to cisplatin administration. Significant suppression of the DNA fragmentation was also demonstrated by densitometry, and measurement of urea nitrogen and creatinine in blood also showed a marked decrease in their respective levels in rats administered ginsenoside-Rd. The present findings suggest that ginsenoside-Rd ameliorates cisplatin-induced renal injury, a process in which apoptosis plays a central role, and thereby causes restoration of the renal function.
Cerebral Hypoxia-Ischemia in Immature Rats: Involvement of Mitochondrial Permeability Transition?
Authors: Puka-Sundvall Malgorzata , Gilland Eric , Hagberg Henrik
Published: April 2003

The aim of this study was to evaluate the involvement of mitochondrial membrane permeability transition (MPT) after hypoxia-ischemia (HI) in 7-day-old rats. [14C]2-deoxyglucose (DOG) was administered to controls, and at various time points after HI. MPT in the cerebral cortex was measured as entrapment of DOG-6-P in mitochondria. Another group of rats was treated with the MPT inhibitor cyclosporin A (CsA; 10–50 mg/kg i.p.) or vehicle before and after HI, and the effect on brain injury and mitochondrial respiration was evaluated. A significant increase in DOG-6-P entrapment in mitochondria indicated that MPT occurred in two phases: a primary MPT after 0–1.5 h and a secondary MPT after 6.5–8 h of reperfusion. However, CsA did not affect brain injury or mitochondrial respiration. The data suggest that MPT occurred after HI but does not provide evidence for its involvement in the development of injury.
Monocyte-Related Determinants of Inflammation in Patients on Peritoneal Dialysis
Authors: Jacobson Stefan H. , Hylander Britta , Thylén Pia , Lundahl Joachim
Published: April 2003

Aims: We studied markers of monocyte activation, i.e., the cell surface expression of CD11b and CD62L, and the serum concentrations of monocyte chemotactic protein 1 (MCP-1; a monocyte-specific chemoattractant) and soluble vascular cell adhesion molecule 1 (sVCAM-1; an adhesion molecule involved in monocyte recruitment) in 20 patients on peritoneal dialysis (PD), in 25 patients with chronic renal insufficiency, and in 27 healthy subjects. Results: Monocytes obtained from the peripheral blood of PD patients had a significantly higher expression of CD62L (p = 0.02) as compared with monocytes from healthy subjects and a lower CD11b/CD18 expression as compared with monocytes collected from healthy subjects (p < 0.001) and from patients with renal insufficiency (p < 0.001). Monocytes from PD patients had, however, the capacity to increase the expression of CD11b following stimulation with a potent chemotactic factor. The serum concentrations of MCP-1 and sVCAM-1 were higher in PD patients (575 ± 51 and 1,517 ± 89 ng/ml) than in healthy subjects (225 ± 17 and 668 ± 64 ng/ml, respectively; p < 0.001 for both comparisons). There was a correlation between the levels of sVCAM-1 and MCP-1 (r = 0.48, p < 0.05) in patients on PD, but neither correlated with the monocyte expression of CD11b/CD18 or CD62L. The concentration of C-reactive protein was higher in patients on PD as compared with healthy subjects and correlated significantly with the concentration of sVCAM-1 (r = 0.63, p < 0.01). Conclusions: Monocytes in the peripheral circulation of patients on PD have a CD62Lhigh/CD11blow phenotype, indicating that they have not undergone complete differentiation. Patients also have an increase in the systemic chemotactic activity for monocytes in combination with increased levels of sVCAM-1 and C-reactive protein. These inflammatory aberrations may play a pathophysiological role in the response to inflammatory and infectious diseases in patients on PD.
IgA Nephropathy, Antineutrophil Cytoplasmic Antibodies and Crescentic Glomerulonephritis in a Patient with the Hermansky-Pudlak Syndrome
Authors: Tagboto Senyo , Carr Sue , Varghese Anitha , Allen Alice , Feehally John , Furness Peter
Published: April 2003

Hermansky-Pudlak syndrome is an uncommon cause of renal dysfunction. Because of the risk of bleeding in this condition, few patients have undergone a renal biopsy. Renal dysfunction has been attributed to the deposition of ceroid pigment in the tubules and interstitial fibrosis. We report a case with renal biopsy findings of ceroid deposition and interstitial fibrosis, but also of mesangial IgA deposition, crescentic glomerulonephritis, and an interstitial lymphocytic infiltrate. Furthermore, perinuclear antineutrophil cytoplasmic antibodies of the IgG subclass were detected in a blood sample. It is well known that ceroid pigment in this syndrome accumulates in monocytes, macrophages and T lymphocytes and it has been suggested that this may affect their function. We suggest that this novel combination of renal changes might be explained on the basis of alterations in immune mechanisms in the Hermansky-Pudlak syndrome.
Diuretics versus Angiotensin-Converting Enzyme Inhibitors in Autosomal Dominant Polycystic Kidney Disease
Authors: Ecder Tevfik , Edelstein Charles L. , Fick-Brosnahan Godela M. , Johnson Ann M. , Chapman Arlene B. , Gabow Patricia A. , Schrier Robert W.
Published: April 2003

Hypertension, which occurs commonly and early in autosomal dominant polycystic kidney disease (ADPKD), affects both renal and patient outcome. However, there is no consensus about the type of antihypertensive therapy that is most appropriate for patients with ADPKD. This historical prospective, nonrandomized study was designed to investigate the effect on renal function of diuretics versus angiotensin-converting enzyme (ACE) inhibitors in hypertensive patients with ADPKD who entered the study with comparable renal function. Among hypertensive ADPKD patients followed in our center, patients taking diuretics without any ACE inhibitors were included in the diuretic group (n = 14, male/female ratio 5/9, mean age 47 years), whereas patients taking ACE inhibitors but no diuretics were included in the ACE inhibitor (ACEI) group (n = 19, male/female ratio 11/8, mean age 41 years). For comparable blood pressure control, 21% of the ACEI group and 64% of the diuretic group (p < 0.05) needed additional antihypertensive medications. After an average follow-up period of 5.2 years, the creatinine clearance decreased significantly in the diuretic group (74 vs. 46 ml/min/1.73 m2, p < 0.0001) and in the ACEI group (83 vs. 71 ml/min/1.73 m2, p = 0.0005). The decrement in creatinine clearance was significantly larger in the diuretic group than the ACEI group (p < 0.05). The annual decrease in creatinine clearance was 5.3 ml/min/1.73 m2 in the diuretic group and 2.7 ml/min/1.73 m2 in the ACEI group (p < 0.05). A significant increase in urinary protein excretion occurred in the diuretic but not in the ACEI group. Hypertensive ADPKD patients treated with diuretics had a faster loss of renal function as compared with patients treated with ACE inhibitors, despite similar blood pressure control. This result will need to be further examined in a randomized study.
Hospitalizations for Bacterial Septicemia after Renal Transplantation in the United States
Authors: Abbott Kevin C. , Oliver, III James D. , Hypolite Iman , Lepler Lawrence L. , Kirk Allan D. , Ko Chia W. , Hawkes Clifton A. , Jones Camille A. , Agodoa Lawrence Y.
Published: April 2003

Background: It is common belief in the transplant community that rates of septicemia in transplant recipients have declined, but this has not been studied in a national population. Methods: Therefore, 33,479 renal transplant recipients in the United States Renal Data System from July 1, 1994 to June 30, 1997 were analyzed in a retrospective registry study of the incidence, associated factors, and mortality of hospitalizations with a primary discharge diagnosis of septicemia (ICD9 Code 038.x). Results: Renal transplant recipients had an adjusted incidence ratio of hospitalizations for septicemia of 41.52 (95% CI 35.45–48.96) compared to the general population. Hospitalizations for septicemia were most commonly associated with urinary tract infection as a secondary diagnosis (30.6%). In multivariate analysis, diabetes and urologic disease, female gender, delayed graft function, rejection, and pre-transplant dialysis, but not induction antibody therapy, were associated with hospitalizations for septicemia. Recipients hospitalized for septicemia had a mean patient survival of 9.03 years (95% CI 7.42–10.63) compared to 15.73 years (95% CI 14.77–16.69) for all other recipients. Conclusions: Even in the modern era, renal transplant recipients remain at high risk for hospitalizations for septicemia, which are associated with substantially decreased patient survival. Newly identified risks in this population were female recipients and pre-transplant dialysis.
Influence of Age on the Prognosis of Renal Transplant Recipients
Authors: Kappes Ulrike , Schanz Georg , Gerhardt Ulf , Matzkies Fritz , Suwelack Barbara , Hohage Helge
Published: April 2003

With aging, morphologic organ changes due to arteriosclerosis, hypertension, or diabetes increase, and renal transplantation tends to become less successful. We analyzed the outcome of transplantation in 123 recipients who underwent renal transplantation between January 1988 and December 1989. We assessed patient and graft survival after 1, 5, and 6 years as well as mortality and transplant failure and the incidence of rejections. We compared the results of patients aged under 60 years (group 1, n = 60) with the findings of patients aged over 60 years (group 2, n = 63). Immunosuppression was with ciclosporin A and prednisolone without exception. In patients under the age of 60, the overall patient survival at 1, 5, and 6 years was 97, 95, and 90% and was significantly compromised in recipients over the age of 60 (92, 80, and 75%). The 1-, 5- and 6-year graft survival rates were 92, 90, and 90% in recipients aged over 60 years and 88, 82, and 79% in recipients under the age of 60 years. The incidence of rejection was significantly higher in recipients under the age of 60. Patient mortality was mainly due to cardiovascular complications and transplant failure mainly related to transplant thrombosis. In older patients, renal transplantation is thought to be an option of survival rate improvement in comparison with hemodialysis. The incidence of transplant rejection is significantly lower, and this indicates a promising result regarding the long-term prognosis. As cardiovascular complications present as the main mortality factors of both transplant and patient, the prognosis is considered to be highly dependent on screening and treatment of these risk factors.
Leukocyte, Platelet and Endothelial Activation in Patients with Acute Renal Failure Treated by Intermittent Hemodialysis
Authors: Pina Oliveira de Sá Helena Manuel , Pinho Lucas Freitas Luís Alberto , Fonseca Alves Vera Cristina , Rebelo Garção Maria Fátima , Santos Rosa Manuel Amaro , Abreu Fernandes Marques Adelino Augusto
Published: April 2003

Background: Using different types of dialysis membranes to treat acute renal failure (ARF), clinical and experimental studies have demonstrated discordant results relatively to the effect of membrane bioincompatibility on patient outcome. Nevertheless, there are few data on the biocompatibility indices in patients with ARF who need to be treated by hemodialysis. Objective: To characterize the impact of intermittent hemodialysis (IHD) on indices of leukocyte, platelet and endothelial activation in patients with ARF. Patients and Methods: We prospectively studied 27 patients with severe ARF treated by IHD. They were characterized relatively to gender, age, ARF etiology, urinary output per 24 h, Simplified Acute Physiology Score (SAPS), number of dialysis sessions and outcome. We evaluated the effect of hemodialysis with two types of low-flux dialyzers (cuprophane and polysulfone dialyzers) on plasma concentrations of soluble TNF-RI (TNF-sR55), TNF-RII (TNF-sR75), interleukin (IL)-6, soluble CD23 molecule, soluble P-selectin and von Willebrand factor (vWF). Results: There were no significant differences between the two groups of patients dialyzed with cellulose-based and synthetic membranes in terms of age, sex, urinary output per 24 h, SAPS, number of dialysis sessions and mortality. We verified high plasma concentrations of TNF-sR55, TNF-sR75, IL-6, sCD23, sP-selectin and vWF in the global population studied. Patients dialyzed with cuprophane membranes showed significantly lower pre- and postdialysis concentrations of sP-selectin than patients dialyzed with polysulfone membranes. After a hemodialysis session, with correction for differences of blood hematocrit, we did not observe any significant modification in the concentrations of TNF-sR55, TNF-sR75, IL-6, sP-selectin and vWF of the plasma. On the other hand, a significant increase of sCD23 molecule was found in the group dialyzed with polysulfone membranes (p = 0.009). Conclusions: The group of 27 patients with ARF who needed IHD, showed increased plasma concentrations of some leukocyte, platelet and endothelial activation markers (TNF-sR55, TNF-sR75, IL-6, sCD23, sP-selectin and vWF). These mediators characterize the inflammatory and procoagulant state associated with this pathologic condition. After a hemodialysis session with these low-flux membranes (cellulose-based and polysulfone membranes), we did not observe any significant variation in the concentrations of TNF-sR55, TNF-sR75, IL-6, sP-selectin and vWF of the plasma. Patients dialyzed with polysulfone membranes presented higher basal plasma concentrations of sP-selectin and significant postdialysis increase of plasma concentrations of CD23 molecule compared to patients dialyzed with cuprophane dialyzers.
Risk Factors for Hypertension in Chronic Hemodialysis Patients: Baseline Data from the HEMO Study
Authors: Rocco Michael V. , Yan Guofen , Heyka Robert J. , Benz Robert , Cheung Alfred K.
Published: April 2003

A cross-sectional analysis was performed to determine risk factors associated with hypertension in 1,238 chronic hemodialysis patients upon enrollment into the HEMO Study. The mean pre- and post-dialysis systolic blood pressure were 152.4 ± 25.0 (mean ± SD) and 137.8 ± 24.6 mm Hg, respectively. The mean pre- and post-dialysis diastolic blood pressures were 82.1 ± 14.8 and 74.7 ± 13.8 mm Hg, respectively. Less than 30% of the study cohort had blood pressures that were normotensive by JNC VI guidelines. Risk factors associated with higher pre- and post-dialysis systolic blood pressures included the presence of diabetes mellitus, older age, increased number of prescribed antihypertensive medications, lower hematrocrit, and absence of arrhythmias. Variables associated with higher pre- and post-dialysis diastolic blood pressures included younger age, increased number of prescribed anti-hypertensive medications and absence of arrhythmias. There was also a nonlinear relationship between blood pressure and prescribed total ultrafiltration volume. A total ultrafiltration volume of >2.5 kg was associated with an elevation in pre-dialysis systolic and diastolic blood pressures. A total ultrafiltration volume of ≤2.5 kg was associated with an elevation in post-dialysis systolic and diastolic blood pressures. These data on ultrafiltration volume suggest that higher pre-dialysis blood pressures may be associated with excessive interdialytic weight gains due to patient noncompliance with fluid restriction and that higher post-dialysis blood pressures may be associated with a prescribed dry weight that is higher than the patient’s true dry weight. Better management of these parameters may improve the prevalence and severity of hypertension in this population.
Heparin-Induced Skin Necrosis in a Patient with End-Stage Renal Failure and Functional Protein S Deficiency
Authors: Denton Mark D. , Mauiyyedi Shamilla , Bazari Hasan
Published: April 2003

Skin ulceration is a well-characterized thrombotic complication of the heparin-induced thrombocytopenia (HIT) syndrome. We present the case of a 73-year-old diabetic woman nearing end-stage renal failure who developed extensive upper thigh, abdominal and buttock ulceration following initiation of subcutaneous heparin for prophylaxis against deep vein thrombosis. A preliminary diagnosis of calciphylaxis was made based on the classical distribution and macroscopic appearance of the ulceration in a patient with end-stage renal failure and secondary hyperparathyroidism. However skin biopsy showed complete absence of calcium deposits in the dermal microvasculature. The presence of extensive microthrombi within dermal vessels prompted serologic testing to detect a prothrombotic state. We identified the combined presence of heparin-dependent platelet activating (HIT) antibodies and functional protein S deficiency. To our knowledge this is the first reported case of a dialysis patient presenting with skin ulceration induced by heparin and protein S deficiency. This case highlights the importance of a skin biopsy and testing for a hypercoaguable state in patients with end-stage renal disease and skin ulceration. We suggest that HIT antibodies should be requested in all dialysis patients presenting with skin ulceration.
Reduction of the Homocysteine Plasma Concentration by Intravenously Administered Folinic Acid and Vitamin B12 in Uraemic Patients on Maintenance Haemodialysis
Authors: Buccianti Gherardo , Bamonti Catena Fabrizia , Patrosso Cristina , Corghi Enzo , Novembrino Cristina , Baragetti Ivano , Lando Giuliana , De Franceschi Michela , Maiolo Anna Teresa
Published: April 2003

Background: Hyperhomocysteinaemia is an independent cardiovascular risk factor which can induce vascular lesions, thus contributing to the early development of atherosclerosis. Low-dose folic acid supplementation reduces the pretreatment homocysteine plasma levels by 25–35%. Recent studies report that higher intravenous or oral administration of the active form of folic acid reduces the homocysteine plasma concentration by nearly 70%. The reduction could also be influenced by the thermolabile variant of methylenetetrahydrofolate reductase (tMTHFR) and by the dialysis modality. Methods: A cross-sectional clinical study was performed to evaluate the effect of a drug containing folinic acid and vitamin B12 on the plasma homocysteine concentration and whether this variable could also be influenced by the presence of a genetic variant of the methionine pathway and the use of different dialysis modalities. The plasma homocysteine concentration was measured in 55 patients undergoing haemodialysis, 27 of whom have been treated intravenously for megaloblastic anaemia using a drug containing low concentrations of folinic acid and vitamin B12 at the end of each dialysis session for 6 months. The presence of tMTHFR was sought by molecular analysis, and the role of the dialysis modality was also investigated. Results: The patients given the folic acid treatment had lower homocysteine plasma levels than those not so treated. The plasma homocysteine concentration was significantly higher in the tMRHFR homozygotes than in the patients with a normal genotype, significantly lower in the treated than in the untreated homozygotes, and significantly higher in the untreated homozygotes than in the untreated subgroup with a normal genotype. The homocysteine level was also significantly lower in the patients who underwent convective haemodialysis than in those who received standard bicarbonate dialysis. Conclusions: A drug containing low concentrations of folinic acid combined with vitamin B12 using an intermittent intravenous regimen is effective in reducing the homocysteine plasma concentration in uraemic patients. The homocysteine levels seem also to depend on genotype and dialysis modality.
IgA Nephropathy and Pulmonary Hemorrhage in an Adult
Authors: Fung Michelle , Churchill David , Alexopoulou Iakovina , Ingram Alistair
Published: April 2003

IgA nephropathy is the most common glomerular disease worldwide, but is generally renal limited or associated with a rash. Pulmonary hemorrhage has been very uncommonly associated with IgA nephropathy, although it is frequently seen in other glomerulonephritides. We describe a well-proven case of IgA nephropathy associated with pulmonary hemorrhage, in which immunosuppressive medication was administered. We also review the literature to make a case for immunosuppression in these rare patients.
Repeated Pregnancies in Patients with Non-Immunoglobulin A Mesangioproliferative Glomerulonephritis
Authors: Malik Ghulam Hassan , Al-Mohaya Suleiman , Shaikh Jamil F. , Al-Wakeel Jamal , Al-Hozaim Waleed , Kechrid Mohammad , Al-Duhami Hessa , Shetia Mohammad Sabry , El Gamal Hazem , Hammed Durdana
Published: April 2003

Aim: To analyze the effect of repeated pregnancies on underlying MesGN and see the reciprocal effect on maternal and fetal outcome. Patients and Methods: Pregnancy records of cases with histological diagnosis of MesGN were reviewed, and past medical histories recorded. Results: Cesarean section (CS). Only two patients developed renal insufficiency after undergoing 5 and 11 pregnancies and follow-up of 9 and 20 years respectively. Conclusion: The outcome of repeated pregnancies in patients with MesGN is comparable to normal deliveries. A higher incidence of pre-eclampsia, LBW babies and CS was noted in the post- compared to the pre-MesGN pregnancies. Repeated pregnancies do not influence the course of the MesGN.
Relationship between Urinary Calcium and Net Acid Excretion as Determined by Dietary Protein and Potassium: A Review
Authors: Lemann Jr. Jacob
Published: April 2003

Increasing urinary net acid (titratable acid + NH4 – HCO–3) excretion is accompanied by an increased urinary Ca excretion because of reduced renal tubular reabsorption of filtered Ca. The relationships between urinary Ca excretion rates and urinary net acid excretion rates are reviewed for data: (1) among healthy adults eating constant diets when net acid excretion is increased by increasing dietary protein, administering NH4Cl, or withdrawal of dietary KHCO3 or reduced by administering KHCO3; (2) among healthy adults eating constant diets providing varying amounts of protein and potassium, and (3) among healthy adults and Ca stone formers with and without idiopathic hypercalciuria eating ad libitum. The results show that urinary Ca excretion varies directly with net acid excretion by 0.035 mmol/mEq. The urinary net acid excretion increases by 0.10–0.15 mEq/mmol urinary urea, and urinary Ca increases by about 0.04 mmol/g dietary protein, while the urinary net acid excretion decreases as the ratio of urinary K/urea, a reflection of the dietary K relative to dietary protein, increases. The relationships between net acid excretion and both urinary urea and K/urea are similar among Ca stone formers without and with idiopathic hypercalciuria, but those with idiopathic hypercalciuria exhibit increased rates of urinary Ca excretion at all levels of net acid excretion.
Ecosystem of the Anticolana Valley
Authors: Prestininzi Alberto , Ludovici Giovanni
Published: April 2003

The results of an integrated environmental study on the geological, hydrogeological and ecological features of the area of formation of the low mineral content water of Fiuggi are briefly presented. The research programme, that was started in 1996 and is now in its final phase, was aimed at the following: (a) identifying the geological-structural limits of the hydrogeological basin; (b) building a model of the deep water circulation that should include an analysis of the rainfall and of the water balance, and (c) determining the vulnerable characteristics of the aquifer in relation to the human impact and setting up a monitoring system to control the different environmental parameters.
High Glucose Increases Inducible NO Production in Cultured Rat Mesangial Cells
Authors: Noh Hyunjin , Ha Hunjoo , Yu Mi Ra , Kang Shin Wook , Choi Kyu Hun , Han Dae Suk , Lee Ho Yung
Published: April 2003

Background/Aim: Increased nitric oxide (NO) generation and action have been suggested to be associated with glomerular hyperfiltration and increased vascular permeability early in diabetes. However, previous studies have primarily focused on the constitutive nitric oxide synthase (cNOS) pathway present in endothelial cells, and the role of the inducible NOS (iNOS) pathway in diabetic nephropathy has remained unclear. This study examined whether high glucose modulates NO synthesis by the iNOS pathway in rat mesangial cells. In addition, the effect of inhibition of the iNOS pathway on fibronectin production was determined to examine the role of the iNOS pathway in high glucose-induced extracellular expansion by mesangial cells. Methods: NO synthesis by the iNOS pathway was evaluated by nitrite and iNOS mRNA and protein productions. The effects of protein kinase C (PKC) inhibitor and aldose reductase inhibitor on the iNOS mRNA expression and aminoguanidine, a relatively specific inhibitor of the iNOS on fibronectin protein production were examined. Results: High 30 mM glucose concentration led to significant increases in nitrite production of rat mesangial cells upon stimulation with lipopolysaccharide (LPS) plus interferon-γ (IFN-γ) compared with control 5.6 mM glucose concentration. Mesangial iNOS mRNA expression and protein production also increased significantly in response to high glucose. The addition of calphostin C, a PKC inhibitor, and 6-bromo-1,3-dioxo-1H-benz[d,e]isoquinoline-2(3H)-acetic acid, an aldose reductase inhibitor, significantly suppressed the enhancement of iNOS mRNA expression in high glucose concentration. High glucose also significantly increased fibronectin protein production of mesangial cells upon stimulation with LPS plus IFN-γ compared to control glucose. Aminoguanidine reversed this high glucose-induced fibronectin production at dose inhibiting iNOS mRNA expression. Conclusions: These results indicate that high glucose enhances cytokine-induced NO production by rat mesangial cells, and that the activation of PKC and aldose reductase pathway may play a role in this enhancement. In addition, high glucose-induced NO production by the iNOS pathway may promote extracellular matrix accumulation by mesangial cells under certain condition.
Report of a Patient with a High Level of Parathyroid Hormone-Related Peptide Associated with Malignant Lymphoma Involving Multiple Bony Lesions
Authors: Kinugawa Naoko , Okimoto Yuri , Teraoka Naoko , Sakao Eiko , Horie Hiroshi
Published: April 2003

Hypercalcemia in malignant lymphoma is not common. Our case of malignant lymphoma with multiple bony lesions showed hypercalcemia (13 mg/dl) at the time of bone marrow relapse. The serum level of parathyroid hormone-related peptide increased to 142 pmol/l, which may be secreted by malignant lymphoma cells. The course of the patient was aggressive and she died from bone marrow relapse after 6 months of treatment including high-dose methotrexate, which caused acute nonoliguric renal failure. At autopsy there was extensive calcium deposition in the lungs, kidneys and pancreas and prominent tubular damage of kidneys.
Cancer-Associated Glycosphingolipid Antigens: Their Structure, Organization, and Function
Authors: Hakomori Sen-itiroh
Published: April 2003

Experimental and human cancers are often characterized by the presence of tumor-associated glycosphingolipid (GSL) antigens defined by monoclonal antibodies. Major progress has been made during the past two decades on structural identification of these antigens. None of these structures are truly ‘tumor-specific’. However, many of the antibodies show preferential or ‘specific’ reactivity with tumors, based on organizational differences of membrane GSLs in tumor cells versus normal cells. Clustered GSL antigens organized with transducer molecules in microdomain have been found recently to comprise a structural and functional unit involved in tumor cell adhesion coupled with signal transduction. Some of the GSL antigens have been identified as adhesion molecules recognized by carbohydrate-binding proteins or by complementary carbohydrates on target cells. Such adhesion, coupled with signaling, may initiate the metastatic process. Elucidating the mechanism of this initial adhesion/signaling step may lead to discovery of therapeutic agents that disrupt adhesion (‘antiadhesion therapy’) or normalize signaling (‘ortho-signaling therapy’). Tumor-associated GSL antigens are also a target in immunotherapy of tumors, including development of antitumor vaccines.
Additional Stem Cell Therapy for Graft Failure after Allogeneic Bone Marrow Transplantation
Authors: Min Chang-Ki , Kim Dong-Wook , Lee Jong Wook , Min Woo Sung , Kim Chun Choo
Published: April 2003

In this study we retrospectively evaluated the effect and outcome of a boost dose of donor stem cells without additional chemotherapy or total body irradiation. Between March 1983 and August 1999, 20 of 788 (2.5%) patients receiving allogeneic bone marrow transplantation (BMT) were treated with an additional boost dose of donor cells. The reasons for the use of the boost treatment were primary graft failure (early rejection; n = 7), secondary graft failure including late rejection (n = 10), refractory pure red cell aplasia caused by the remaining recipient cells producing anti-erythrocyte antibodies (n = 2), and donor lymphocyte infusion induced pancytopenia (n = 1). The patients were aged from 17 to 48 years (median age 31 years). The underlying diseases of the patients were severe aplastic anemia in 12 patients, acute myelogenous leukemia in 3, acute lymphocytic leukemia in 3, and chronic myelogenous leukemia in 2. The donors were human leukocyte antigen-identical siblings in 18 cases, 1 mismatched related donor, and 1 unrelated donor. The cell source was bone marrow in 6 cases and peripheral blood progenitor cells in 14. The median interval between BMT and the boost treatment was 7 weeks (range 1–124). No conditioning regimen was given prior to the boost treatment for 11 patients, while 4 received total nodal irradiation (TNI) plus antithymocyte globulin (ATG), 3 ATG alone, and 2 TNI plus steroid. The median infused booster mononuclear cell dose was 2.55 × 108/kg (range 0.28–37.0). Fifteen (75%) patients achieved a hematological recovery. After the boost treatment, 6 of 20 (30%) patients developed acute graft-versus-host disease (GVHD) ≧ grade II, 3 of whom had had prior GVHD. Five (31.3%) of the evaluable 16 patients developed chronic GVHD. The GVHDs were easily controlled using immunosuppressive agents except in the case of 1 patient. Five patients died after the boost treatment; 2 within 30 days, 2 within 60 days, and 1 after 32 months. The causes of death were: 3 engrafment failures, 1 late rejection, and 1 infection following GVHD. With a median follow-up of 31.5 months (range 6–92), the Kaplan-Meier method estimated that the overall survival rate 1 and 3 years after the boost treatment was 80 and 71%, respectively. The survival of patients with primary graft failure was determined to be significantly lower compared to that of patients with secondary graft failure, using the log rank test (p = 0.0176). Disease category, stem cell source, conditioning prior to a boost treatment, and year of boost treatment did not have an influence on survival. We conclude that the reinfusion of donor stem cells is frequently successful in achieving engraftment with rare occurrence of fatal GVHD. Furthermore, relatively good long-term survival was demonstrated.