bluuebunny/crossref_metadata_2025 huggingface dataset:
Cell Adhesion Molecule Expression in Murine Lupus-Like Nephritis Induced by Lipopolysaccharide
Authors: Baran Dana , Vendeville Benoît , Ogborn Malcolm , Katz Nili , Rubin Evelyn , Nguyen Vi
Published: April 2003

Background: Intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule (VCAM) are thought to play important roles in leukocyte recruitment to the kidney. We therefore chose to study mesangial cell adhesion molecule expression in vitro, and the role of these molecules in experimental lupus-like nephritis. Methods and Results: When cultured murine mesangial cells were stimulated with interferon-γ (IFγ) and tumor necrosis factor-α (TNFα), mRNA levels for ICAM-1 and VCAM markedly increased. These molecules were detected at the cell surface by flow cytometry. Since lipopolysaccharide (LPS) stimulates TNFα and IFγ production in vivo, we treated mice with Streptococcus minnesota LPS in order to study renal adhesion molecule expression. LPS treatment induced mesangial proliferative glomerulonephritis characterized by leukocyte infiltration, and increases in total glomerular cellularity, volume and matrix area. mRNA levels for ICAM-1 and VCAM were increased in the kidneys of LPS-treated versus control mice. ICAM-1 and VCAM molecules were constitutively expressed in renal vascular endothelium. At 3 and 5 weeks, this vascular staining intensified, and some ICAM-1 and VCAM expression was induced in the glomerular mesangium. ICAM-1 and VCAM induction occurred early and correlated in time with leukocyte infiltration. Conclusion: Interactions between cell adhesion molecules expressed by intrinsic glomerular cells and infiltrating leukocytes play a role in the initiation of LPS-induced lupus-like nephritis. These observations are potentially relevant to the understanding and treatment of certain types of human glomerulonephritis.
Plasma Concentration of Uroguanylin in Patients on Maintenance Dialysis Therapy
Authors: Fukae Hiroko , Kinoshita Hiroshi , Fujimoto Shouichi , Nakazato Masamitsu , Eto Tanenao
Published: April 2003

Background: Uroguanylin, originally isolated from urine, is a new natriuretic peptide. Its plasma level is increased in association with renal impairment and fluid retention in patients with renal diseases. Methods: Uroguanylin concentrations were measured in patients on hemodialysis (HD, n = 76) and those on continuous ambulatory peritoneal dialysis (CAPD, n = 10) using a sensitive ra- dioimmunoassay for human uroguanylin. Results: Plasma concentrations of immunoreactive (ir)-uroguanylin in the patients on HD and CAPD (212.0 ± 17.4 and 245.3 ± 39.5 fmol/ml) were significantly higher than the value for the normal controls (5.0 ± 0.3 fmol/ml). Plasma ir-uroguanylin levels before the start of regular HD were correlated with predialysis excess weight based on their dry weights (r = 0.33, p < 0.01) and with dialysis duration (r = 0.26, p < 0.05). The plasma levels in patients with HD, for whom high-flux membranes were used, were decreased at the end of regular HD as compared with the prior levels (p < 0.05), but not in those who underwent HD with conventional membranes. Conclusion: These findings suggest that the plasma ir-uroguanylin level is related to the patient’s volume status as well as renal impairment. Whether the accumulation of uroguanylin has a pathological effect has yet to be determined.
Protective Role of Extracellular Superoxide Dismutase in Hemodialysis Patients
Authors: Yamada Harutaka , Yamada Yasukazu , Adachi Tetsuo , Fukatsu Atsushi , Sakuma Masato , Futenma Arao , Kakumu Shinichi
Published: April 2003

Background: The superoxide anion and other oxygen radicals have been implicated in the progression of chronic renal failure, and are removed by extracellular superoxide dismutase (EC-SOD) in the extracellular space on the surface of the endothelium. A single-base substitution of the EC-SOD gene which reduces the binding capability to endothelial cells resulting in an increased serum concentration, has been identified in healthy persons and hemodialysis patients. Results: The proportion of patients with this mutation among hemodialysis patients in each 20 months’ duration after the initiation of hemodialysis was retrospectively studied. The percentage of substitution-positive patients declined 80 months after the start of hemodialysis in non-DM patients. In contrast, in DM patients, the rapid decrease was obvious as early as 40 months after the initiation of hemodialysis. By prospective study for 5 years, there were significant differences in the survival rate between patients with and without R213G in DM, but not in non-DM patients. Among those who died, the incidence of ischemic heart disease and cerebrovascular disease in cases with R213G was significantly higher than in cases without R213G. Conclusion: These results suggest that the presence of a substitution in the EC-SOD gene at the heparin-binding domain could be a prognostic marker of dialysis patients.
Predictive Value of Repeat Renal Biopsies in Children with Nephrotic Syndrome
Authors: Ahmad Hadi , Tejani Amir
Published: April 2003

In children who exhibit a frequently relapsing course of minimal change disease (MCD), treatment is often difficult and frustrating to the physician and the family since the goal of a sustained remission remains elusive. The progression of the disease is often unpredictable from its clinical presentation since the lesion of MCD may evolve into a more severe form, such as mesangial IgM nephropathy or focal segmental glomerulosclerosis (FSGS), without alteration in signs and symptoms. Alkylating agents such as cyclophosphamide, or immunosuppressives such as cyclosporine can induce a more sustained remission, but are fraught with inherent toxicity, which makes difficult the decision to use these drugs in patients with MCD. Over a 10-year period we studied 49 patients who had more than one renal biopsy. Repeat biopsies were performed either to delineate the morphological lesion prior to change in therapy, or to confirm suspected drug toxicity, which would necessitate discontinuation of therapy. A total of 83 repeat biopsies were performed in these 49 patients. Of the 49 patients, 25 had MCD, and in 21 of these the lesion evolved into either IgM nephropathy (n = 7) or FSGS (n = 14). Of patients with IgM nephropathy (n = 12), 50% evolved into FSGS. The clinical diagnosis made prior to the repeat biopsy did not confirm with the histological diagnosis in 43% of cases, and a change in therapy or cessation of therapy was carried out in 43 of 83 repeat biopsy instances. Since the complications were mild and the ability of clinical findings to accurately predict the histological lesion limited, we conclude that repeat renal biopsies are a useful tool to fashion optimal therapy in children with frequently relapsing nephrotic syndrome.
Water Immersion Increases Urinary Excretion of Aquaporin-2 in Healthy Humans
Authors: Buemi Michele , Corica Francesco , Di Pasquale Giuseppe , Aloisi Carmela , Sofi Marilena , Casuscelli Teresa , Floccari Fulvio , Senatore Massimino , Corsonello Andrea , Frisina Nicola
Published: April 2003

Many previous studies have shown that aquaporin-2 (AQP2), the vasopressin-regulated water channel, is excreted in the urine and that the excretion increases in response to vasopressin. Moreover, recently a close correlation between AQP2 excretion in urine and kidney AQP2 expression has been demonstrated, showing that urinary excretion of AQP2 is a reliable indicator for AQP-2 function. As head-out water immersion causes an expansion in the central vascular volume equal to that induced by 2 liters of saline, without modifying plasma composition, we used immersion in water to evaluate if the response to acute expansion of the central vascular volume could involve vasporessin (AVP) and AQP2. In healthy subjects, concentrations of plasma atrial natriuretic factor (ANF) and AVP, and urinary AQP2 were measured during a 2-hour immersion period. In all subjects, immersion caused a prompt and marked increase in immunoreactive ANF (23.0 ± 2.12 pg/ml at second hour vs. 2.17 ± 0.42 pg/ml at baseline) and in urinary excretion of AQP2 (23.9 ± 2.69 pmol/mg creatinine at second hour vs. 4.42 ± 0.14 pmol/mg creatinine at baseline), while a significant decrease was found in plasma AVP. Recovery was associated with a prompt return to pre-study levels. These findings demonstrate that heat-out water immersion stimulates urinary excretion of AQP2 in absence of an increase in plasma AVP.
Hyperlipidemic Nephropathy Induced by Adriamycin in Ovariectomized Rats: Role of Free Radicals and Effect of 17-Beta-Estradiol Administration
Authors: Montilla P. , Túnez I. , Muñoz M.C. , Delgado M.J. , Salcedo M.
Published: April 2003

The present study in rats evaluates the effects of the ovariectomy (OVX) with and without the simultaneous administration of 17β-estradiol (17βE2) on oxidative stress and hyperlipidemic nephropathy induced by a single high dose of adriamycin (AD). OVX enhances oxidative stress and worsens nephropathy induced by AD. These changes are prevented by simultaneous administration of 17βE2. OVX alone induced oxidative stress and hyperlipidemia without biochemical evidence of renal dysfunction. Our results revealed that ovarian hormones, especially estrogens, have a protective effect against oxidative stress and nephropathy induced by AD. Since the reactive oxygen species plays a role in the pathogenesis of renal lesion, it is important to emphasize that estrogens and their hydroxylated compounds function as biological antioxidants.
Proliferative Responses of Mesangial Cells to Growth Factors during Compensatory versus Dietary Hypertrophy
Authors: Weissgarten J. , Modai D. , Berman S. , Cohn M. , Galperin E. , Averbukh Z.
Published: April 2003

While the bulk of renal hypertrophy induced by contralateral nephrectomy or a high-protein diet consists of tubular cell growth, there is some evidence suggesting that mesangial cells play a role in this phenomenon. Previous data suggest that this role of mesangial cells is associated with their proliferation. We, therefore, undertook this investigation to assess the proliferative responses of mesangial cells, originating from single remaining kidneys or from kidneys of rats fed a high-protein diet, to epinephrine, endothelin, arginine vasopressin, neo-synephrine, or epidermal growth factor (EGF). All agents significantly enhanced the proliferation of normal mesangial cells, though the responses to neo-synephrine and EGF were significantly lower as compared with the other growth promoters. The mitogenic effects of the first three agents on single kidney mesangial cells were significant, but blunted as compared with control cells. This blunting was not evident in the case of the latter two mitogens. A significant enhancement of proliferation of mesangial cells originating from protein-fed rats was produced by epinephrine, neo-synephrine, and EGF. These effects were statistically not different from those observed in normal mesangial cells. The proliferative response to each of the mitogens used in the study proved highly specific for each mitogen, since it was abolished by respective specific inhibitors. Mesangial cells may play a role in the activation and later in progressive inhibition of renal hypertrophy in vivo.
Transient and Sequential Expression of Chemokine mRNA in Glomeruli in Puromycin Aminonucleoside Nephrosis
Authors: Ou Zhou Luo , Natori Yumiko , Natori Yasuhiro
Published: April 2003

Chemokines are a large family of low-molecular-weight proinflammatory cytokines that stimulate recruitment of leukocytes. We previously reported that among six chemokines, the expression of mRNAs for MCP-1, MCP-3, TCA3, and MIP-1α, but not for MIP-1β and RANTES, was markedly elevated in the renal cortex of rats with puromycin aminonucleoside induced nephrosis. In this study we have determined the glomerular expression of the chemokine mRNAs in this model using quantitative competitive reverse-transcriptase polymerase chain reaction. After an injection of puromycin aminonucleoside, the number of monocytes/macrophages and CD4+ and CD8+ cells markedly increased by day 5 and increased thereafter until day 10. The levels of mRNAs for MCP-1, MCP-3, and lymphotactin increased on day 5 and returned to their normal levels by day 7. The level of TCA3 mRNA increased on day 3, and that of MIP-1α mRNA increased on day 7, but both returned to their normal levels within 2 days. No increase in the mRNAs of MIP-1β or RANTES was observed until day 10. These results indicate that the expression pattern of the chemokine mRNAs in glomeruli resembles that in renal cortex, but is more transient and sequential.
Successful Interventional Treatment of Renal Insufficiency Caused by Renal Artery Pseudoaneurysm with Concomitant Arteriovenous Fistula
Authors: Barkhausen J. , Verhagen R. , Müller R.-D.
Published: April 2003

Asymptomatic arteriovenous fistulae and pseudoaneurysms are common after renal biopsy. We present a patient with a single kidney and symptomatic pseudoaneurysm of the renal artery with concomitant arteriovenous fistula as a rare complication following surgical embolectomy. The patient developed renal insufficiency because of a significant degree of vascular steal caused by the fistula. Dialysis was performed for more than 6 months until the fistula was diagnosed. The fistula and the pseudoaneurysm were successfully treated by superselective arterial embolization with metallic coils. Renal function improved within the next 2 weeks and no further dialysis was necessary.
The Obsession with High Dietary Protein Intake in ESRD Patients on Dialysis: Is It Justified?
Authors: Uribarri J.
Published: April 2003

Background: The belief that dialysis patients require a much higher intake of protein than the average person is widely held among nephrologists and a recent editorial review on the care of patients undergoing hemodialysis advised a protein intake of at least 1.5 g/kg/day in this population. In theory, the requirements for daily protein intake of dialysis patients should be the same as normals plus whatever extra obligatory nitrogen losses are imposed by the dialytic process. Since the average loss of protein and/or amino acids is about 8 g/day in peritoneal dialysis and 8 g per session in hemodialysis patients, the daily intake of protein in dialysis patients needs to be increased only by this small magnitude. Methods: All the literature reporting on nitrogen balance data on different protein intakes in chronic maintenance dialysis patients was reviewed and analyzed. Results: There were 3 balance studies adressing this issue in hemodialysis patients and 6 in peritoneal dialysis patients. These data show that dialysis patients are in nitrogen balance even with a protein intake as low as 0.7 g/kg/day. Conclusions: The nitrogen balance data confirm that in stable dialysis patients a safe requirement of protein intake is about 1 g/kg/day and attempts at increasing protein intake beyond this value are not warranted. The persistent recommendation of a high dietary intake of protein for dialysis patients may reflect the influence of two other issues: the belief that dialysis is a catabolic event, and the data showing an inverse correlation between protein intake and outcome.
Urinary Retinol-Binding Protein as a Prognostic Marker in the Treatment of Nephrotic Syndrome
Authors: Mastroianni Kirsztajn Gianna , Nishida Sonia K. , Silva Marcelo S. , Ajzen Horacio , Pereira Aparecido B.
Published: April 2003

We studied the urinary levels of retinol-binding protein (urRBP), an index of proximal tubular dysfunction, in patients with nephrotic syndrome before and approximately 2 months after the beginning of steroid therapy as a predictor of response to therapy which included for some patients courses of immunosuppressive drugs. Those patients with minimal-change disease, mesangial proliferative glomerulonephritis, and focal-segmental glomerulosclerosis who had normal pretreatment urRBP levels were responsive to treatment; occasionally, responsive patients had an initially elevated urRBP level which normalized during treatment. Contrariwise, those patients with abnormally high levels of urRBP which did not normalize during treatment did not respond to treatment. The chance of a patient with minimal-change disease, mesangial proliferative glomerulonephritis, or focal-segmental glomerulosclerosis and a pretreatment urRBP level equal to or >1.0 mg/l being resistant to steroid treatment is 30 times that of a patient with a urRBP level <1.0 mg/l and even higher, if we consider the levels obtained during treatment.
Oral Supplementation with γ-Linolenic Acid Extracted from Mucor circinelloides Improves the Deformability of Red Blood Cells in Hemodialysis Patients
Authors: Iijima Shigeruko , Otsuka Fujio , Kikuchi Hiroshi , Yamada Keiko , Nakajima Toshiaki , Yahiro Kenichi , Kondo Akihiro
Published: April 2003

Background: The development of abnormalities in red blood cell (RBC) deformability in patients undergoing hemodialysis remains a major problem, because it is related to peripheral microcirculation, oxygen supply, and various complications in such patients. γ-Linolenic acid (GLA; 18:3n-6), one of the polyunsaturated fatty acids and a precursor of prostaglandin E1, is reported to have a favorable effect on the deformability of circulating blood cells in diabetic patients. Methods: In order to clarify the efficacy of GLA on RBC deformability in 7 patients undergoing maintenance hemodialysis, we examined in a pilot study the changes in the deformability of RBC and the changes in the phospholipid fatty acid composition in both plasma and RBC membrane before and after high-dose oral supplementation with GLA derived from Mucor circinelloides for 12 weeks. Results: Before supplementation, the micropore passage time of RBC suspension, which is an indicator of RBC deformability, in these patients was markedly longer than that in healthy control subjects. After administering GLA, the prolonged passage time of the patients both rapidly and steadily decreased and nearly reached control levels. Light microscopic observations of RBCs using Giemsa stain revealed a decreased number of poikilocytes after supplementation. An analysis of the fatty acid composition before treatment and 8 weeks after starting the treatment showed the dihomo-γ-linolenic acid (DGLA; 20:3n-6) level in the plasma to have increased (p < 0.05), while the arachidonic acid (AA; 20:4n-6) concentration in the RBC membrane decreased (p < 0.05). The level of DGLA in the RBC membrane, the level of GLA, and the ratio of GLA + DGLA/AA in plasma and RBC membrane did not change significantly; however, these all tended to increase. Conclusion: The results of this pilot study indicate that the oral supplementation of GLA extracted from M. circinelloides improves the poor RBC deformability in hemodialysis patients, partly by inducing changes in the composition of fatty acids in plasma and RBC membrane.
Moderate Metabolic Acidosis and Its Effects on Serum Parameters in Hemodialysis Patients
Authors: Gao Hubin , Lew Susie Q. , Bosch Juan P.
Published: April 2003

We screened the laboratory data of 50 chronic hemodialysis patients selected randomly over a 21-month period to generate 158 data points which identified two groups: (1) those with a predialysis total CO2 concentration less than or equal to 19 mEq/l (data A; n = 57) and (2) those with a predialysis total CO2 concentration greater than 19 mEq/l (data B; n = 101). Then, both groups were compared for the following parameters: predialysis blood urea nitrogen (BUN), serum phosphorus, uric acid, creatinine, and albumin concentrations, Kt/V, urea reduction ratio, normalized protein catabolic rate, dry weight, ultrafiltration, blood flow and dialysis flow rates, duration of dialysis treatment, and blood pressure. Group data A had significantly higher predialysis BUN, phosphorus, and uric acid concentrations than group data B. There were significant inverse correlations between predialysis serum bicarbonate and predialysis BUN, phosphorus, and uric acid concentrations. Although it is not clear what the long term side effects of moderate metabolic acidosis are, we recommend its correction.
Constant, but Not Pulsed Calcitriol Suppresses Hemodialysis Patients’ Antigen-Induced Lymphocyte Proliferation
Authors: Hannula Päivi M. , Antonen Jaakko A. , Saha Heikki H.T. , Koivisto Anna-Maija , Krohn Kai J.E. , Pasternack Amos I.
Published: April 2003

Background/Aims: In vitro constant calcitriol [1,25-(OH)2D3] inhibits healthy individuals’ T lymphocyte proliferation at supraphysiological concentrations. In contrast, among hemodialysis patients, intravenous 1,25-(OH)2D3 pulse therapy of secondary hyperparathyroidism has been shown to be even immunostimulatory. We studied the effect of in vitro constant and intermittent 1,25-(OH)2D3 on lymphocyte antigen response of hemodialysis patients. Methods: Twelve hemodialysis patients’ peripheral blood mononuclear cells were stimulated with purified protein derivative of tuberculin (12.5, 25 and 50 mg/l) or tetanus toxoid (TT; 1,000, 5,000 and 10,000 Lf/l, limit of flocculation) for 7 days. Constant 1,25-(OH)2D3 was added to all cultures at concentrations of 0, 10–10 or 0.25 × 10–9 mol/l (0, 42 and 105 ng/l) and to half of the cultures additionally as a 0.75 × 10–9 mmol/l (315-ng/l) pulse on the 5th culture day. Results: TT-induced lymphocyte proliferation was statistically related to a constant 1,25-(OH)2D3 concentration (p = 0.001, analysis of variance). With constant 1,25-(OH)2D3 concentrations of 0, 42 and 105 ng/l, the TT-induced responses were 1.53, 1.44 and 1.40 log cpm, respectively (mean of TT concentrations). The responses of the (additionally) pulse-treated cells [1.65, 1.50 and 1.40 log cpm; concentrations of constant 1,25-(OH)2D3 as above] were similar to those of the nonpulsed cells. Thus constant, but not pulsed 1,25-(OH)2D3 decreased the TT responses. On the purified protein derivative of tuberculin response, neither constant nor pulsed 1,25-(OH)2D3 had any significant effect. Conclusions: The decline of TT response with constant 1,25-(OH)2D3 corresponds with findings on immunosuppressive action of 1,25-(OH)2D3 in previous studies done on normal subjects’ cells. This was not seen with intermittently applied 1,25-(OH)2D3. These results support the previous concept that intermittent 1,25(OH)2D3 therapy is not immunosuppressive in hemodialysis patients.
Molecular Biology of Transplantation
Authors: Krensky Alan M.
Published: April 2003

The past decade has witnessed an explosion in our understanding of the molecules involved in transplant rejection and acceptance. This review highlights our current understanding of antigen recognition, signal transduction, and effector mechanisms of the immune system. Such information has proven important in understanding the action of immunosuppressive drugs and will prove useful in the design of new immunotherapies.
Predictors of Final Adult Height after Renal Transplantation during Childhood: A Single-Center Study
Authors: Rodríguez-Soriano Juan , Vallo Alfredo , Quintela María Jesús , Málaga Serafín , Loris César
Published: April 2003

Aim: Assessment of final adult height and its predictive factors in children transplanted (RTx) and followed up in a single center. Methods: A cohort of 32 patients (17 boys, 15 girls) who received RTx before the age of 15 years and had reached a final adult height was selected. Twenty patients received a single RTx, 9 patients received two RTx, and 3 patients received three RTx. Seven children were transplanted preemptively, while the remaining 25 children received peritoneal dialysis for relatively short periods of time. In 11 patients, recombinant human growth hormone (rhGH) was administered either before (n = 8) or after (n = 3) RTx. Results: In 13 patiens (41%), the final height standard deviation score for chronological age (hSDS) was –2.3±0.5, below the 95% confidence limits for target height (group A), while in 19 patients (59%), it was –0.7±0.8, within the 95% confidence limits for target height (group B). The hSDS values at the start of dialysis and at the time of first RTx were significantly lower in group A than in group B. A higher hSDS at the start of dialysis and at the time of first RTx had a significant positive influence on the final height (FH), whereas a longer duration of dialysis had a significant negative effect on the FH. Administration of rhGH after RTx played an important role in the achievement of a normal FH in 3 girls. No differences were observed between group A and B with respect to age at start of dialysis, chronological or bone age at first RTx, number of rejection episodes, duration of the study period from last RTx to FH, glomerular filtration rate during this study period, or percentage of time on prednisone therapy. Conclusions: The FH is almost exclusively predetermined by the height achieved at the start of dialysis and at the time of first RTx. Therefore, to reach target adult height after RTx, the best strategy is to shorten the time of dialysis and to start rhGH administration at a young age and as early as possible during the course of chronic renal failure. Administration of rhGH after RTx is also highly effective, but, given its potential danger, still remains a matter of investigation.
Hyperleptinemia Is Not Correlated with Markers of Protein Malnutrition in Chronic Renal Failure
Authors: Rodríguez-Carmona Ana , Pérez Fontán Miguel , Cordido Fernando , García Falcón Teresa , García-Buela Jesús
Published: April 2003

Background: Serum leptin levels are increased in chronic renal failure (CRF) and may potentially contribute to protein malnutrition in this disorder. Method: Following a cross-sectional design, we performed a nutritional survey in a wide sample of uremic patients treated conservatively (n = 87), with peritoneal dialysis (n = 71) and with hemodialysis (n = 53). Then, we analyzed the correlation between serum leptin levels and markers of protein malnutrition. We used a multivariate approach, taking into consideration the confounding effect of other factors on the correlation between hyperleptinemia and protein malnutrition. Main Results: Both univariate and multivariate analysis disclosed a poor correlation between hyperleptinemia and markers of protein malnutrition. In fact, there were trends to a positive correlation between leptinemia and body protein stores, as estimated from the scrutinized markers. Persistence of the basic correlation between general intake, fat mass and leptin in CRF could partially explain these findings, but neither a negative correlation between leptin levels nor protein nutritional state could be disclosed after controlling for this factor. Conclusions: Our results do not support a first-line role for hyperleptinemia in the genesis of protein malnutrition of uremia.
Association of Anticardiolipin Antibodies with Vascular Access Occlusion in Hemodialysis Patients: Cause or Effect?
Authors: Haviv Y.S.
Published: April 2003

Background: Uremic patients on hemodialysis (HD) often display occlusive disorders despite their uremic thromboasthenia. The role of anticardiolipin antibodies (aCL) and the recently identified anti-β2-glycoprotein I antibodies (aβGPI) in these phenomena is unknown. Methods: The prevalence of IgG and IgM aCL and aβGPI was documented in 54 HD patients and 19 nondialyzed patients with chronic renal failure (CRF). The HD patients were further divided into arteriovenous (AV) access occluders and nonoccluders. Results: HD patients had a higher mean IgG aCL level than CRF patients (14.68 ± 3 vs. 2.96 ± 1 IU/ml, respectively, p < 0.0007). IgM aCL did not differ significantly. AV access occluders had a higher mean IgG and IgM aCL levels than nonoccluders (24.47 and 8.39 IU/ml in occluders vs. 8.45 and 3.59 IU/ml in nonoccluders, p < 0.0226 and p < 0.05, respectively). IgM and IgG aβGPI antibody levels were below the cutoff point and did not differ significantly between the various groups. Cardiovascular episodes were not correlated with the titer of aCL or aβGPI. Conclusion: These results indicate that HD, especially in patients with recurrent access occlusion episodes, is associated with elevated levels of IgG aCL, and that IgG aCL level may predict the occlusive status of HD patients.
Cardiovascular Mortality in Haemodialysis Patients Treated with Epoetin Beta – A Retrospective Study
Authors: Möcks J.
Published: April 2003

Aims: Anaemia is a major risk factor in end-stage renal disease (ESRD) and leads to enhanced cardiac output and left-ventricular hypertrophy (LVH). Recombinant human erythropoietin (rhEPO) partially corrects anaemia and reduces LVH in ESRD. The current study retrospectively analysed mortality data from haemodialysis patients included in the clinical development database for epoetin-β. Methods: The unselected database, set up to monitor safety from clinical studies of epoetin-β, comprised 3,111 adult haemodialysis patients included in 17 clinical trials in the clinical development programme (1987–1994). 1,726 and 466 patients were treated for >1 and >2 years, respectively. Untreated control patients (n = 246) were available in two studies. Mortality was measured from fatal adverse event documentation. Results: The controlled studies showed an approximately 20% reduction in the mortality risk for epoetin-β versus controls after 1 year. For the overall patient population, all-cause mortality fell from a peak (after about 150 days) of about 10 to about 6 deaths per 100 patient-years in the 3rd year of treatment (p < 0.01). The proportion of deaths due to cardiovascular causes fell from 50 to 20–30% over 3 years. The decline in cardiovascular mortality could not be explained by changes in covariate distribution or by drop-outs. Conclusions: The cardiovascular mortality risk decreased over time in this population of ESRD patients. The beneficial effects of long-term anaemia correction by epoetin-β therapy was a likely cause of this favourable development.
Significant Suppressive Effect of Low-Dose Temocapril, an ACE Inhibitor with Biliary Excretion, on FGS Lesions in Hypertensive Rats
Authors: Suyama Katsuo , Muso Eri , Yashiro Masatomo , Sasayama Shigetake
Published: April 2003

To investigate how the interruption of the renin-angiotensin system (RAS) and reduction of blood pressure (BP) affect the lesions of chronic focal and segmental glomerulosclerosis (FGS), we studied the effects of high and low doses of angiotensin-converting enzyme inhibitors (temocapril – TEM) a newly developed ACE inhibitor with biliary tract excretion, on the hypertensive model of FGS. A high dose of TEM significantly lowered BP and suppressed both intense proteinuria and glomerular extracapillary lesions including macrophage infiltration. On the other hand, although a low dose of TEM did not significantly lower BP throughout the experimental period, it prevented renal lesions almost in the same manner as high-dose TEM with suppression of c-myc gene expression in glomeruli. These findings suggest that in PAN-induced chronic FGS, the systemic BP elevation could not be the major factor for the progression of renal damage which TEM could prevent without significant lowering of BP.
Successful Pregnancy in a Patient with Polycystic Kidney Disease and Advanced Renal Failure without Prophylactic Dialysis
Authors: Hassan K. , Weissmam I. , Osman S. , Gery R. , Oettinger M. , Shasha S.M. , Kristal B.
Published: April 2003

Pregnancies in women suffering from advanced chronic renal failure are frequently associated with deterioration of maternal renal function, premature births and low birth weights. Prophylactic dialysis is sometimes instituted since this intervention ameliorates the uremic milieu and improves maternal status and fetal uterine environment. This report describes a successful pregnancy and delivery in a hypertensive woman with advanced chronic renal failure due to polycystic kidney disease without accelerating the natural deterioration of renal function and without instituting prophylactic dialysis. The infant was delivered at full term with a normal birth weight. Thirty months after delivery, growth and development of the child were normal and the rate of deterioration of maternal renal function, assessed by 1/creatinine, was unaffected by pregnancy. Conservative management and effective control of blood pressure may be sufficient to achieve successful pregnancy outcome when women with advanced chronic renal failure become pregnant.
L-Lysine Reduces Nonenzymatic Glycation of Glomerular Basement Membrane Collagen and Albuminuria in Diabetic Rats
Authors: Jyothirmayi G.N. , Modak R. , Reddi A.S.
Published: April 2003

In this study, we examined the hypothesis whether exogenous administration of L-lysine in drinking water would reduce nonenzymatic glycation of glomerular basement membrane (GBM) collagen and thus albuminuria in streptozotocin-diabetic rats. The rationale is that the administered lysine would combine with the circulating glucose and make it unavailable to react with Ε-amino groups of lysine of various proteins in these diabetic rats. Lysine (0.1%) was given to diabetic rats 7 days (early treatment) or 90 days (late treatment) after induction of hyperglycemia. The treatment was continued for 60 days. Diabetic rats had significantly higher glucose, glycosylated HbA1, kidney weight, nonenzymatic glycation of GBM collagen, albuminuria, and systolic blood pressure than normal rats. Early treatment with lysine prevented the rise in glycosylated HbA1 (normal 6.98 ± 0.71% vs. diabetic – early treatment – 7.78 ± 1.50%; p = NS), reduced glycosylation of GBM collagen by 86%, and significantly improved albuminuria. There was no significant effect on plasma glucose and systolic blood pressure. However, late treatment reduced the glycosylation of GBM collagen by 46% with a significant improvement in albuminuria. Plasma creatinine levels were not different between normal and untreated diabetic or lysine-treated diabetic rats; however, the creatinine clearance was significantly higher in all groups of diabetic rats (normal 0.45 ± 0.09 vs. diabetic 2.02 ± 0.39 ml/min; p < 0.001). The data suggest that early rather than late treatment is more beneficial in reducing nonenzymatic glycation of collagen, although both treatments significantly reduced albuminuria. There was no nephrotoxicity as assessed by plasma creatinine levels or creatinine clearances. These beneficial effects occurred independent of changes either in blood pressure or plasma insulin concentration.
Effects of Endothelin Receptor Antagonists on the Progression of Diabetic Nephropathy
Authors: Hocher Berthold , Schwarz Anja , Reinbacher Daniel , Jacobi Jaqueline , Lun Andreas , Priem Friedrich , Bauer Christian , Neumayer Hans-H. , Raschack Manfred
Published: April 2003

Background: Diabetic nephropathy is the leading cause of end-stage renal disease in European countries and is associated with an enhanced renal synthesis of endothelin (ET)-1. ETs are – beside its potent vasoconstrictor properties – very potent profibrotic acting paracrine hormones especially in the kidney. Methods: We analyzed in rats with streptozotocin-induced diabetes the effects of an ETA-type (ETA) receptor antagonist (LU 135252) in comparison to a combined ETA/ETB receptor antagonist (LU 224332) on the expression of interstitial and glomerular collagen type I, III and IV as well as on fibronectin and laminin by quantitative immunohistochemistry using a computer-aided image analysis system. Global glomerular matrix deposition was analyzed after PAS staining. In addition to the morphometric examination of the kidneys, we also investigated GFR, urinary albumin and total protein excretion. The diabetic rats were treated for 36 weeks. Results: Treatment with either LU 135252 or LU 224332 normalized the amount of PAS-positive material within the glomeruli. The expression of glomerular fibronectin and type IV collagen was increased 36 weeks after induction of diabetes. The overexpression of these two matrix proteins within the glomeruli of diabetic rats was completely abolished by both ET receptor antagonists, whereas protein excretion was only reduced by about 50% as compared to diabetic rats without treatment. Conclusion: The present study indicates that ETA receptor antagonists as well as combined ETA/ETB receptor antagonists reduce proteinuria and completely normalize the renal matrix protein expression in hyperglycemic rats with streptozotocin-induced diabetes. The antifibrotic effect seems to be mediated via the ETA receptor. ET receptor antagonists might be a new approach in the treatment of diabetic nephropathy.
Direct Effect of the Correction of Acidosis on Plasma Parathyroid Hormone Concentrations, Calcium and Phosphate in Hemodialysis Patients: A Prospective Study
Authors: Movilli Ezio , Zani Roberta , Carli Orsola , Sangalli Luisa , Pola Alessandra , Camerini Corrado , Scolari Francesco , Cancarini Giovanni C. , Maiorca Rosario
Published: April 2003

Background: Metabolic acidosis contributes to renal osteodystrophy and together with hyperphosphatemia, hypocalcemia and altered vitamin D metabolism may result in increased levels of intact parathyroid hormone (iPTH) and metastatic calcifications. However, the impact of the correction of metabolic acidosis on iPTH levels and calcium-phosphate metabolism is still controversial. Study Design: The effects of the correction of metabolic acidosis on serum concentrations of iPTH, calcium (Ca), phosphate (PO4) and alkaline phosphatase were prospectively studied. Twelve uremic patients on maintenance hemodialysis (HD) for 49 months (median; range 6–243 months) with serum bicarbonate levels ≤20 mmol/l were studied before and after 3 months of oral sodium bicarbonate supplementation. Predialysis serum bicarbonate, arterial pH, ionized calcium, plasma sodium, plasma potassium, serum creatinine, hemoglobin, Kt/V, postdialysis body weight, predialysis systolic and diastolic blood pressure were also evaluated before and after correction. Results: Serum bicarbonate levels and arterial pH increased respectively from 19.3 ± 0.6 to 24.4 ± 1.2 mmol/l (p < 0.0001) and 7.34 ± 0.03 to 7.40 ± 0.02 (p < 0.001). iPTH levels decreased significantly from 399 ± 475 to 305 ± 353 pg/ml (p = 0.026). No changes in total serum Ca, plasma PO4, serum akaline phosphatase, Kt/V, serum creatinine, hemoglobin, body weight, predialysis systolic and diastolic blood pressures were observed. iCa decreased significantly. Conclusions: Our study demonstrates that the correction of metabolic acidosis in chronic HD patients reduces iPTH concentrations in HD patients with secondary hyperparathyroidism possibly by a direct effect on iPTH secretion.
Platelet-Activating Factor Antagonist, SM-12502, Attenuates Experimental Glomerular Thrombosis in Rats
Authors: Hayashi Junichi , Hiromura Keijyu , Koizumi Ryuichi , Shimizu Yukihiro , Maezawa Akira , Nojima Yoshihisa , Naruse Takuji
Published: April 2003

Platelet-activating factor (PAF) is involved in many pathologic conditions through its potent proinflammatory and vasoactive effects. Using a specific PAF antagonist, SM-12502, we investigated the role of PAF in rat experimental glomerular thrombosis. In this model, sequential injections of nephrotoxic serum (NTS) and lipopolysaccharide (LPS) selectively induce glomerular fibrin deposition accompanied by neutrophil accumulation. SM-12502, when injected simultaneously with either NTS or LPS, strongly inhibited glomerular fibrin deposition in a dose-dependent manner. In contrast, neutrophil invasion was similar in both SM-12502-injected and uninjected rats, suggesting that the antithrombotic effect was not mediated by inhibition of neutrophil migration. However, serum myeloperoxidase activity, a marker of neutrophil activation, was significantly suppressed by treatment with SM-12502. From a previous finding supporting the indispensable role of neutrophils in this model and the current observations, SM-12502 is suggested to attenuate glomerular thrombosis by inhibiting neutrophil activation. Thus, the present findings suggest an involvement of PAF in this glomerular thrombosis model.
Nadroparin-Induced Calcinosis cutis in Renal Transplant Recipients
Authors: van Haren F.M.P. , Ruiter D.J. , Hilbrands L.B.
Published: April 2003

Low-molecular-weight heparins are routinely used to prevent deep venous thrombosis following renal transplantation in our department. We report 2 patients who developed tender erythematous subcutaneous nodules with induration, ulceration and necrosis at the site of subcutaneous administration of nadroparin. Both patients were renal transplant recipients with impaired graft function and high serum calcium-phosphate products. The diagnosis calcinosis cutis was confirmed by technetium-99m bone scan and by histological examination of biopsies. Both patients showed spontaneous recovery several weeks after discontinuation of nadroparin. Patients with chronic renal failure and hyperphosphatemia may be predisposed to develop calcinosis cutis. In addition, the role of the calcium content of nadroparin is discussed.
Upregulation of Fractalkine in Human Crescentic Glomerulonephritis
Authors: Furuichi Kengo , Wada Takashi , Iwata Yasunori , Sakai Norihiko , Yoshimoto Keiichi , Shimizu Miho , Kobayashi Ken-ichi , Takasawa Kazuya , Kida Hiroshi , Takeda Shin-ichi , Matsushima Kouji , Yokoyama Hitoshi
Published: April 2003

Background/Aim: To evaluate the importance of fractalkine, a novel member of the CX3C chemokine, and natural killer (NK) cells in human crescentic glomerulonephritis, we determined the presence of fractalkine in the diseased kidneys immunohistochemically, and the correlation among fractalkine, NK cells and the degree of renal damage. Methods: Twenty-three patients (13 males and 10 females) with primary or secondary crescentic glomerular disease were evaluated in this study. Fractalkine and CD16-positive cells including NK cells were detected immunohistochemically. Results: Fractalkine-positive cells were detected in the interstitium of 23 patients with crescentic glomerulonephritis, while they were not detected in the glomeruli. In addition, CD16-positive cells were detected in both the glomeruli (1.3 ± 0.2/glomerulus) and interstitium (1.3 ± 0.2/visual field). The number of fractalkine-positive cells in the interstitium correlated with the number of CD16-positive cells before glucocorticoid therapy (r = 0.43, p = 0.047, n = 23). The number of fractalkine-positive cells in the interstitium before glucocorticoid therapy (0.2 ± 0.1/visual field) decreased after therapy (0.1 ± 0.1/visual field, p = 0.050) in 11 cases tested. The number of CD16-positive cells in the diseased kidneys did not change after glucocorticoid therapy. Conclusion: These results suggest that the local production of fractalkine may explain the presence of CD16-positive cells including NK cells, which may participate in the interstitial lesions of human crescentic glomerulonephritis before corticoid therapy.
Inheritance of a Stable Mutation in a Family with Early-Onset Disease
Authors: Perrichot R.A. , Mercier B. , de Parscau L. , Simon P.M. , Cledes J. , Ferec C.
Published: April 2003

Autosomal/dominant polycystic kidney disease (ADPKD) exhibits a high inter- and intrafamilial heterogeneity partly explained by the involvement of at least 3 different genes in the disorder transmission. PKD1, the major locus, is located on chromosome 16p. The occurrence of very early-onset cases of ADPKD (sometimes in utero) in a few PKD1 families or the increased severity of the disease in successive generations raise the question of anticipation. This is a subject of controversial discussion. This report deals with the molecular analysis in families with very early-onset ADPKD. The finding of the same stable mutation with such different phenotypes rules out a dynamic mutation. The molecular basis of severe childhood PKD in typical ADPKD families remains unclear; it may include segregation of modifying genes or unidentified factors and the two-hit mechanism.
Sialyl Lewis X and Anti-P-Selectin Antibody Attenuate Lipopolysaccharide-Induced Acute Renal Failure in Rabbits
Authors: Hayashi Hirotsugu , Imanishi Noriaki , Ohnishi Masako , Tojo Shinichiro J.
Published: April 2003

Background/Aim: Acute renal failure (ARF) is one of the common problems associated with sepsis or multiple organ dysfunction syndrome (MODS). We have investigated the effects of inhibiting selectin-mediated cell adhesion on lipopolysaccharide-induced ARF in rabbits, using sialyl Lewis X oligosaccharide and PB1.3, an anti-human P-selectin monoclonal antibody, as inhibitors. Methods: ARF was induced by intravenous administration of lipopolysaccharide (0.3 mg/kg, i.v. bolus injection) to New Zealand White rabbits. Induction of ARF was characterized by increases in blood urea nitrogen (BUN), creatinine, and the number of polymorphonuclear leukocytes infiltrating glomeruli, and by fibrin deposition in glomeruli, and tubular dilatation in the kidney. Sialyl Lewis X oligosaccharide (14 mg/kg, i.v. bolus injection immediately before lipopolysaccharide administration and 9 mg/kg/h, i.v. infusion) or PB1.3 (5 mg/kg, i.v. bolus injection before lipopolysaccharide administration), anti-P-selectin antibody, were treated. Results: Treatment with sialyl Lewis X oligosaccharide inhibited the increases in BUN, creatinine, and the number of infiltrating polymorphonuclear leukocytes, and attenuated histopathological impairments. Similarly, treatment with PB1.3 prevented some of the characteristics associated with lipopolysaccharide-induced ARF, not but the increase in creatinine. Conclusion: These results suggest that selectin inhibitors, including sialyl Lewis X oligosaccharide and PB1.3, may provide clinical benefits in the prevention of ARF associated with sepsis and MODS. To our knowledge, this is the first report that P-selectin is directly involved in lipopolysaccharide-induced ARF in rabbits.
Pathogenesis of Focal Glomerulosclerosis
Authors: Bolton W. Kline , Abdel-Rahman Emaad
Published: April 2003

Focal segmental glomerulosclerosis (FSGS) is the histologic expression of diverse processes affecting the renal glomeruli and occurring in primary and secondary forms. A number of pathogenic factors have been identified in primary FSGS, and multiple etiologies have been defined as contributing factors for the development of secondary FSGS. There is a complex interplay between etiologic and pathogenic factors, progression factors and intervention in the phenotypic expression of FSGS. Key components include genetic predisposition, environmental influences and the impact on phenotype of pharmacologic intervention. The phenotypic spectrum for FSGS ranges from mild proteinuria and slow progression to a devastating clinical syndrome characterized by heavy proteinuria and rapid loss of renal function over a period of months. While the pathogenesis is unknown, much is known about factors which are involved in the development and progression of both primary and secondary FSGS. The ultimate goal of understanding pathogenesis is to provide specific nontoxic therapy for those patients who have a definable form of FSGS. While this goal is not yet in sight, many types of intervention, not addressed in the current chapter, can influence the course of various diseases presenting as FSGS. Until specific therapy can be fashioned, it is necessary for the clinician caring for these patients to appreciate the complex interaction of pathogenetic factors involved in the development and pregression of FSGS, as a rationale for providing intervention to prevent development of the disease and to slow its course.