bluuebunny/crossref_metadata_2025 huggingface dataset:
Expression of the Molecule Detectable by Anti-Propolypeptide of von Willebrand Factor Antibody in Rat Mesangial Cells in Anti-Thy 1.1 mAb 1-22-3 Induced Glomerulonephritis: A Marker of Injured Mesangial Cells
Authors: Wakasugi Minako , Kawachi Hiroshi , Omori Saori , Takagi Junichi , Nishi Shinichi , Arakawa Masaaki , Shimizu Fujio
Published: April 2003

We have previously reported that propolypeptide of von Willebrand factor (pp-vWF) binds to collagen with an affinity comparable to that of mature vWF, inhibits collagen-induced platelet aggregation, is cross-linked with laminin, and also serves as a ligand for very-late antigen 4 integrin. These observations from in vitro experiments suggest that pp-vWF is incorporated in the extracellular matrix and affects the cell-matrix interaction and that pp-vWF functions in leukocyte recruitment to inflammatory and vascular injury sites. We, therefore, hypothesize that pp-vWF might be involved in the induction and/or progression of mesangial proliferative glomerulonephritis. To test this hypothesis, we examined the kinetics of the immunostaining of the molecule detectable by an affinity-purified anti-pp-vWF antibody in rat glomeruli in monoclonal antibody 1-22-3 induced glomerulonephritis. Immunostaining by pp-vWF antibody was observed in the nuclear rim of mesangial cells in monoclonal antibody 1-22-3 induced glomerulonephritis. Positive staining first appeared on day 10 after monoclonal antibody injection, when mesangial cell proliferation and mesangial matrix expansion had already begun. Staining was still detected on day 56, when morphologic alterations observed by light microscopy had been normalized. The pp-vWF antibody recognized molecule appeared later than α-smooth muscle actin or collagen type I. Positive staining was not detected in cultured mesangial cells. It should be noted that the positive staining by pp-vWF antibody in mesangial cells was still detected in previously injured glomeruli that have almost recovered normal morphology. These observations indicate that positive staining by pp-vWF antibody could be a very useful marker for identifying a past episode of injury in mesangial cells.
Increased Prevalence of Apolipoprotein E3/E4 Genotype among Swedish Renal Transplant Recipients
Authors: Roussos Louis , Florén Claes-Henrik , Carlson Joyce , Svensson Peter J. , Wallmark Anders , Ekberg Henrik
Published: April 2003

There is increasing evidence that lipoproteins are involved in the progression of kidney diseases and in the deterioration of kidney transplant function, although the exact mechanism is still not known. Common polymorphisms of apolipoprotein E genotype associate with the variability of lipoprotein levels and composition. We have, therefore, determined the apolipoprotein E genotype in a group of 112 renal transplant patients, of whom 27 had had an episode of acute vascular rejection, while 85 had not. We found no difference in apolipoprotein E genotype distribution or in relative allele frequency in the vascular rejection group as compared with the group without vascular rejection. The apolipoprotein E genotype distribution in the transplant group was also compared with that in a group of 407 healthy Swedish individuals. The E3/E4 genotype occurred with a significantly increased frequency in the transplant group: 38.3 versus 16% in the control group (p < 0.001). The prevalence of individuals carrying the Ε4 allele among the transplant group was also significantly higher (44%) as compared with the control group (30%; p < 0.01). This increase was entirely due to the predominant increase of E3/E4, as the E4/E4 genotype was less frequent in transplant recipients than in normal controls (3.5 vs. 10.6%; p < 0.05). The relative frequencies of Ε2 (0.044), Ε3 (0.716), and Ε4 (0.238) alleles in the renal transplant group were not different from those of normal controls (0.078, 0.718, and 0.202, respectively). With regard to the prevalence of E4/E4 in the two groups, the lack of difference in the relative frequency of the Ε4 allele must be interpreted with caution. The results thus suggest that the E3/E4 genotype may be associated with the progression of kidney disease leading to renal insufficiency. However, the apolipoprotein E genotype does not seem to influence the risk of vascular rejection among transplant recipients.
Immunogold Labelling of Cytokines in Glomeruli in Children with Various Renal Diseases
Authors: Nakajima Mitsuru , Kawahara Shingo , Sakagami Yoshitugu , Takagawa Ken , Akazawa Hideki , Kamitsuji Hidekazu , Yoshioka Akira
Published: April 2003

Precise localization of cytokines such as transforming growth factor-β (TGF-β), tumor necrosis factor-α (TNF-α), interleukin (IL)-1 and IL-6 was observed in glomeruli using immunogold electron microscopy in 21 children with various types of renal diseases. The distribution pattern of these cytokines, as well as immunoglobulins, C3c and fibrinogen (Fg), was essentially confined to the electron-dense deposits (EDDs) regardless of their location. Frequency of positive labelling of each cytokine was different among various types of renal disorder, that is, TGF-β was found mainly in lupus nephritis (LN), membranous nephropathy and IgA nephropathy, TNF-α in LN, and IL-1 in Henoch-Schönlein purpura nephritis. IL-6 was detected only in 1 case of LN. TNF-α was also found in the cytoplasm of glomerular epithelial cells. Furthermore, in order to evaluate the relation of cytokines to mesangial expansion, extracellular matrix components such as type IV collagen, laminin and fibronectin were stained. The result was that there was no significant correlation between the signal intensity or distribution pattern of cytokines and that of extracellular matrix components. These findings indicate that these cytokines could be associated with the formation of EDDs together with immunoglobulins, C3c and Fg. The involvement of each cytokine in renal pathophysiology might also depend upon the type of renal disease. They also raise the possibility that the glomerular epithelial cells might produce or absorb TNF-α. However, these results did not show significant correlation between cytokine involvement and mesangial expansion.
The Possible Role of c-fos Protein in Hypothalamus in Sleep Disturbance in Chronic Uremic Rats
Authors: Kim Young Ok , Choi Euy Jin , Ahn Hee Jong , Park Cheol Whee , Yang Chul Woo , Jin Dong Chan , Kim Yong Soo , Chang Yoon Sik , Bang Byung Kee
Published: April 2003

Sleep disturbance is very common in patients with chronic renal failure, but its mechanism is not clear. The activity of c-fos protein (FOS) in ventrolateral preoptic neurons (VLPO) is associated with the sleep pattern. The purpose of this study was to evaluate the relationship between sleep disturbance and the expression of FOS in VLPO of chronic uremic rats. Chronic uremia was induced by the 5/6 nephrectomized model. The movements of the rats were measured with infrared monitoring during the daytime (8.00–20.00) and nighttime (20.00–8.00). Rats were killed at 10.00 or 16.00 h for the daytime (uremic rats 7, control 8) and at 22.00 h for the nighttime (uremic rats 7, control 9). The expression of FOS in VLPO was examined with the immunohistochemical method. The number of recorded daytime movements in uremic rats was significantly higher than in control rats (458 ± 185 vs. 222 ± 41, p < 0.001), but the number of recorded nighttime movements in uremic rats was lower than in control rats (949 ± 430 vs. 1,618 ± 261, p < 0.001). In the daytime, the number of FOS immunoreactive cells in uremic rats was lower than in control rats (18.4 ± 5.3 vs. 42.8 ± 6.3, p < 0.001), but there was no difference between two groups in the nighttime (10.8 ± 8.4 vs. 12.5 ± 5.1, p = 0.62). There was a strong negative correlation between the number of recorded movements and the number of FOS immunoreactive cells in VLPO (r = –0.700, p < 0.001). This finding suggests that sleep disturbances in chronic uremic rats might be related to the decreased expression of FOS in VLPO.
Type IV Phosphodiesterase Inhibitor Is Effective in Prevention and Treatment of Experimental Crescentic Glomerulonephritis
Authors: Tam Frederick W.K. , Smith Jennifer , Agarwal Sangita , Karkar Ayman M. , Morel Delphine , Thompson Elizabeth M. , Pusey Charles D.
Published: April 2003

Background: Tumour necrosis factor alpha (TNF-α) has an important role in acute glomerular inflammation. Rolipram, a type IV phosphodiesterase inhibitor, has multiple anti-inflammatory effects including inhibition of TNF-α synthesis. Methods: We investigated the effects of rolipram in prevention and delayed treatment of crescentic glomerulonephritis in Wistar Kyoto rats. Glomerulonephritis was induced by injection of nephrotoxic serum. Results: In the preventive study, rolipram (6.25 mg/kg i.p. twice daily) was started 2.5 h before injection of nephrotoxic serum. Rolipram reduced the expression of TNF-α in glomeruli and renal tubules and abrogated glomerular injury on day 4 (99.7% reduction in albuminuria and 96.4% reduction in fibrin deposition). In the delayed-treatment experiment, rolipram was started 4 days after injection of nephrotoxic serum. Rolipram reduced renal excretion of TNF-α by 63% on day 7. TNF-α was not detected in the sera of treated or control rats. Delayed treatment was effective in crescentic glomerulonephritis, as shown by reduction in albuminuria by 38.1%, fibrin deposition by 60.8%, and crescent formation by 67% on day 7. Conclusions: Rolipram is effective both in prevention and treatment of experimental crescentic glomerulonephritis. This was associated with a reduction of renal production of TNF-α.
Effects of Postdialysis Urea Rebound on the Quantification of Pediatric Hemodialysis
Authors: Marsenić Olivera , Pavličić Dubravka , Bigović Gordana , Peco-Antić Amira , Jovanović Olga
Published: April 2003

Urea rebound (UR) causes single pool urea kinetic modeling (UKM), which is based on end-dialysis urea instead of its equilibrated value (Ceq), to erroneously quantify hemodialysis (HD) treatment. We estimated the impact of postdialysis UR on the results of formal variable volume single pool (VVSP) UKM [Kt/V, urea distribution volume (V), urea generation rate (G), normalized protein catabolic rate (nPCR), and urea reduction ratio (URR)] in children on chronic HD. Thirty-eight standard pediatric HD sessions in 15 stable patients (9 female, 6 male) aged 14.5 ± (SD) 3.28 years were investigated. The HD sessions lasted 3.75 ± 0.43 h. The single pool urea clearance was 4.84 ± 1.25 ml/min/kg. All HD sessions were evaluated by VVSP and URR (%) with postdialysis urea taken at the end of HD and with Ceq taken 60 min after the end of HD, incorporating double pool effects and representing true double pool values. The anthropometric V was calculated by Cheek and Mellits formulae for children. VVSP significantly overestimated Kt/V by 0.26 ± 0.18 U (1.68 ± 0.36 vs. 1.42 ± 0.30, p < 0.0001), i.e., 19.05 ± 13.07%, G/V (0.20 ± 0.04 vs. 0.18 ± 0.04, p < 0.0001), nPCR (1.26 ± 0.23 vs. 1.18 ± 0.22 g/kg/day, p < 0.0001), and URR (73.92 ± 6.49 vs. 69.22 ± 7.06, p < 0.0001). VVSP significantly underestimated kinetic V in comparison to anthropometric V (18.74 ± 4.04 vs. 20.76 ± 4.43 liters or expressed as V/body weight: 58 ± 8 vs. 65 ± 9%, p < 0.05), while double pool kinetic V was more accurate (21.45 ± 4.34 liters, V/body weight: 64 ± 6%, p > 0.05). We conclude that UR has a significant effect on all results of UKM even after standard pediatric HD, and the degree of this efffect is documented. We suggest an increase of the minimum required prescribed single pool Kt/V in children and reduction of any delivered single pool Kt/V by approxiamtely 0.26 Kt/V U. Overestimation of nPCR by approximately 0.08 g/kg/day and underestimation of V by 8.5% should be kept in mind.
Incidence of Acquired Renal Cysts in Biopsy Specimens
Authors: Liu Jian She , Ishikawa Isao , Horiguchi Takayasu
Published: April 2003

Aims: This study investigated whether or not acquired renal cysts develop in patients with mild chronic renal failure. Methods: A retrospective study was carried out using renal biopsy specimens from 720 patients. A renal cyst was defined as a tubule dilated >200 µm. Results: Renal cysts were found in 21 of 720 renal biopsy specimens. Serum creatinine of 21 patients with renal cysts was significantly higher than that of 699 patients without cysts (2.59 ± 2.64 vs. 1.09 ± 0.79 mg/dl) (p < 0.0001). Poor renal function (serum creatinine >1.6 mg/dl) reveals more cyst formation on biopsy specimens than good renal function (serum creatinine <1.5 mg/dl). Cysts were observed in 11 of 607 (1.8%) patients less than 50 years of age and in 10 of 113 (8.8%) patients over 51 years. To exclude simple cysts which are commonly observed in older subjects, 11 patients under 50 years of age were extensively examined. Mean serum creatinine was 2.98 ± 3.06 mg/dl (0.7–10.4 mg/dl). These 11 patients revealed low creatinine clearance of 47.5 ± 25.6 ml/min (5–71 ml/min). Creatinine clearances in 7 patients were 52–71 ml/min (serum creatinine 0.7–2.0 mg/ dl). One of 11 biopsy specimens with cysts was examined by immunohistochemistry on lectin. This specimen was positive for tetragonolobus lectin and negative for peanut lectin, suggesting that the epithelial cells lining the cyst were derived from proximal tubules, unlike those of simple cysts. Conclusion: These results suggest that low normal renal function such as creatinine clearances 52–71 ml/min due to nephron loss is sufficient to induce acquired cyst development in various renal diseases.
IgA Nephropathy and Reiter’s Syndrome
Authors: Satko Scott G. , Iskandar Samy S. , Appel Richard G.
Published: April 2003

Immunoglobulin A (IgA) nephropathy is the commonest type of primary glomerulonephritis worldwide. It has previously been reported in association with the seronegative spondyloarthropathies (ankylosing spondylitis, Behcet’s syndrome, psoriatic arthritis, Reiter’s syndrome and the postenteritic arthritides). Since this condition was first described in 1968, 5 previous case reports of biopsy-proven IgA nephropathy associated with Reiter’s syndrome have been published in the English-language literature. Here we report 2 more such cases, along with a review of the literature describing the association of IgA nephropathy and a number of other immune-complex-mediated glomerulonephritides with the seronegative spondyloarthropathies.
Protective Effect of Pyruvate upon Cultured Mesothelial Cells Exposed to 2 mM Hydrogen Peroxide
Authors: Shostak Avshalom , Gotloib Lazaro , Kushnier Raisa , Wajsbrot Valery
Published: April 2003

Rat peritoneal mesothelial cells in culture have the capability of generating hydrogen peroxide. Exposure of these cells to glucose-enriched, lactated-buffered fluids for peritoneal dialysis significantly increases the production of H2O2. Increased liberation of oxygen radicals also involves the risk of damaging the peritoneal membrane. Pyruvate being a natural oxidant scavenger abundantly present in mammalian cells, we hypothesized that its protective effects facing H2O2 can eventually be of relevance for the mesothelial monolayer of patients on long-term peritoneal dialysis. So far, we designed an experimental study in which rat peritoneal mesothelial cells in culture were exposed to 2 mM H2O2. Cell damage was estimated in terms of decreased capability of the mitochondrial dehydrogenases to reduce MTT. Addition of 2 mM sodium pyruvate to the medium prevented the negative effect of hydrogen peroxide. The MTT/protein values for the control group were 0.00357 ± 0.00075. The ratio after exposure to 2 mM H2O2 was 0.00217 ± 0.00028, whereas that detected in cells incubated in H2O2 plus pyruvate was 0.00325 ± 0.0082 (p < 0.05). These results indicate that pyruvate protected rat peritoneal mesothelial cells in culture against oxidant injury. These data are one more piece of evidence pointing at pyruvate as a potentially useful buffer for peritoneal dialysis solutions.
Relationship of Lipoprotein(a) and Its Phenotypes with the Albumin Excretion Rate in Diabetic Patients: A Multivariate Analysis
Authors: Hernández Cristina , Chacón Pilar , Martí Ramón , García-Pascual Luis , Mesa Jordi , Simó Rafael
Published: April 2003

Background/Aim: The possible association between lipoprotein(a) [Lp(a)] and albumin excretion rate (AER) is a topic that has generated conflicting views. The aim of this study was to determine the relationship between serum Lp(a) concentrations and AER in diabetic patients, taking into account Lp(a) phenotypes in a multivariate analysis. Methods: For this purpose 191 consecutive diabetic patients (69 type 1 and 122 type 2) were included in the study. Lp(a) was determined by ELISA and its phenotypes by SDS-PAGE followed by immunoblotting. Lp(a) phenotypes were grouped by size in small (F, B, S1, S2), big (S3, S4) and null. Results: Diabetic patients with an AER >20 µg/min presented higher Lp(a) concentrations than patients with an AER <20 µg/min: median 19 mg/dl versus 5 mg/dl (p < 0.0001). The differences remained at a significant level when the type of diabetes was considered. A linear correlation was observed between Lp(a) concentration and AER (type 1: r = 0.32, p = 0.01; type 2: r = 0.25, p < 0.05). The AER was independently correlated with Lp(a) concentrations in a multiple regression analysis (p < 0.01), and Lp(a) was independently associated with the presence of diabetic nephropathy in the logistic regression analysis. The overall frequency distribution of Lp(a) phenotypes differed significantly between patients with or without microalbuminuria (p < 0.05). In addition, the AER (µg/min) was different among the Lp(a) phenotypes: small 55 ± 122 (median 4.9), big 58 ± 123 (median 5.7) and null 3 ± 2 (median 2.3); p = 0.01. The significant difference mainly resulted from low AER (<10 µg/min) detected in all patients with the null phenotype. Conclusions: In diabetic patients the serum Lp(a) concentration is associated with AER. Thus, the elevated cardiovascular risk observed in diabetic patients with a high AER could be related to the Lp(a) concentration. Finally, patients with the null Lp(a) phenotype can be considered as a group at low risk of the development of diabetic nephropathy.
Polymorphism of the Angiotensin-Converting Enzyme Gene in End-Stage Renal Failure Patients
Authors: Aucella Filippo , Vigilante Mimmo , Margaglione Maurizio , Grandone Elvira , del Popolo Annamaria , Forcella Mauro , Procaccini Deni , Salatino Giovanna , Passione Antonio , Ktena Maria , De Min Alva , Stallone Carmine
Published: April 2003

The plasma levels of angiotensin-converting enzyme (ACE) are modulated by the insertion (I)/deletion (D) polymorphism within the ACE gene locus. An association between progressive renal disease, raised cardiovascular risk, and ACE plasma levels has been shown. To evaluate the genotype frequencies of the I/D polymorphism in terminal renal failure, we have enrolled 341 dialysis patients (321 on hemodialysis and 20 on peritoneal dialysis) in a district of southern Italy (Foggia). As controls, 1,307 subjects from the same area have been enrolled. Genomic DNA was obtained from leukocytes, and the ACE I/D polymorphism was determined by polymerase chain reaction. Among uremics, 151 subjects (44.3%) carried the DD genotype, 149 (43.7%) the ID, and 41 (12.0%) the II genotype. In controls, 560 subjects (42.8%) had the DD genotype, 577 (44.1%) the ID, and 170 (13.1%) the II genotype (p = n.s.). Among patients, the frequency of DD subjects was higher in men (48.3%) than in women (39.7%, p < 0.01). A slight different frequency of the DD genotype was found according to the duration of dialysis treatment: 47.5% in patients on dialysis up to 60 months and 41.7 and 40.6% in those with a dialytic age of 60–120 and >120 months, respectively (p for trend: 0.53). Patients with or without cardiovascular diseases, such as hypertension, left ventricular hypertrophy, coronary artery disease, and chronic cardiac failure, did not exhibit any difference in ACE I/D allele and genotype frequencies (p always >0.05). In conclusion, frequencies of the ACE DD genotype were similar in uremics and in controls and did not differ between patients with and without cardiovascular diseases. A nonsignificant inverse relationship with the time spent on dialysis was observed, suggesting that ACE I/D polymorphism may influence the cardiovascular death rate.
Reduction of Neutrophil Activation by Vitamin E Modified Dialyzer Membranes
Authors: Omata Momoyo , Higuchi Chieko , Demura Reiko , Sanaka Tsutomu , Nihei Hiroshi
Published: April 2003

Background/Aim: Transient leukopenia during hemodialysis due to neutrophil activation is attributed to bioincompatibility of the dailysis membrane, but the mechanism remains unclear. We studied the mechanism of neutrophilic activation by comparing a vitamin E modified membrane (CLEE) and a regular cellulose membrane (CLSS). Methods: (1) CLSS and CLEE membranes were used in a crossover clinical study in 7 chronic hemodialysis patients. Neutropenia, CD11b expression, and plasma C3a and myeloperoxidase concentrations were compared between the two dialyzer membranes. (2) Normal blood was circulated through CLEE and CLSS minimodels, and the same parameters were compared. (3) Blood samples with modified complement activities (EDTA: both classical and alternative pathways inactivated; EGTA+Mg: classical pathway inactivated; heating: alternative pathway inactivated; control: no modification) were incubated in the CLSS minimodel, and the neutrophilic activation was compared. Results: In clinical hemodialysis, neutropenia, CD11b expression, and C3a and myeloperoxidase levels were significantly lower when CLEE membranes were used. The same tendency was observed in minimodels. However, the degrees of inhibition in clinical dialysis, especially at the venous line, were significantly higher than in minimodels. As compared with controls, CD11b expression and myeloperoxidase level were significantly lower when both classical and alternative pathways were inactivated or when the classical pathway alone was inactivated, but were not significantly different when the alternative pathway alone was inactivated. Conclusions: Vitamin E modification of the dialyzer reduces some reactions of neutrophilic activation, such as CD11b expression and myeloperoxidase release, more effectively in the clinical situation than in ex vivo models, suggesting a possible effect of vitamin E in inhibiting bioreactions due to pyrogen in the dialysate. The classical complement pathway is required in membrane-induced neutrophilic activation, at least during the initial stage.
Assessing Residual Renal Function and Efficiency of Hemodialysis – an Application for Urographic Contrast Media
Authors: Sterner G. , Frennby B. , Månsson S. , Ohlsson A. , Prütz K.G. , Almén T.
Published: April 2003

Background: In patients on hemodialysis with end-stage renal disease there is an increasing interest in measuring both residual renal function (RRF) and quantity and quality of dialysis because insufficient dialysis gives higher mortality. For that purpose we have measured clearances of two urographic iodine (I) contrast media (CM) with different molecular masses (iohexol 821 u and iodixanol 1,550 u). These CM are filtered through glomeruli and dialysis membranes and have higher molecular masses than urea and creatinine and might represent the dialyzability of the hypothetic uremic toxins with a molecular mass of 300–5,000 u. Methods: Thirteen patients (8 of them were anuric) immediately after hemodialysis received 15 ml iohexol (300 mg I/ml i.v.) and 2 weeks later in the same way 15 ml iodixanol (320 mg I/ml). Nine other patients (2 anuric) received CM after only one dialysis; 8 got iohexol and 1 got iodixanol. After the CM injections the iodine concentrations were measured with X-ray fluorescence in blood and, when available, urine during the following 2 days including both the start and end of the next dialysis. Eighteen patients after two dialysis sessions, 2 weeks apart, received 10 ml iohexol i.v., and a single blood sample was taken at the start of the next dialysis 2 days later to determine RRF alone. Results: In the 10 anuric patients the extrarenal clearances (mean ± SD) were 2.5 ± 1.1 and 2.7 ± 1.1 ml/min/1.73 m2 for iohexol and iodixanol, respectively. In patients with RRF good correlations were demonstrated between body clearance, based on two blood samples, and renal clearance of CM. Good correlations (r2 = 0.853 for iohexol, r2 = 0.933 for iodixanol) were noted between two-sample and single-sample body clearances. Repeated single sample iohexol clearances gave a coefficient of variation of 15%. During dialysis the clearances of iohexol and iodixanol were, respectively, 69 ± 16 and 58 ± 11 ml/min/1.73 m2 when calculated from a single-pool model (hemodialysis clearance of CM from plasma). A median increase (rebound) of CM concentrations in plasma 45 min dialysis was 8% for iodixanol and 18% for iohexol. When the CM concentration 45 min after dialysis was used, the clearance values were by 8–10% lower and represented the hemodialysis clearance of CM from the extracellular compartments. The dialysis eliminations of iohexol and iodixanol were similar to that of urea, measured as percentage reduction of serum levels during dialysis. Conclusions: A single injection of CM at the end of dialysis followed by a single blood sample at the start of the next dialysis gives total body clearance, i.e., an estimation of the RRF. An additional blood sample at the end of the next dialysis gives dialysis efficiency.
Intracerebral Abscess Caused by Nocardia otitidiscaviarum in a Renal Transplant Patient – Cured by Evacuation plus Antibiotic Therapy
Authors: Hartmann Anders , Halvorsen Carl Erik , Jenssen Trond , Bjørneklett Arvid , Brekke Inge B. , Bakke Søren J. , Hirschberg Henry , Tønjum Tone , Gaustad Peter
Published: April 2003

We present a 50-year-old female who experienced generalized convulsion 3 months after a successful cadaveric renal transplantation. The first cerebral CT scan indicated cerebral frontal infarction. Repeat CT some days later revealed progressive lesions, and a highly malignant tumor or abscess was suspected. Antifungal and broad-spectrum antibacterial therapy was initiated. Cerebral MRI could not differentiate between these conditions, but a neutrophil granulocyte scan strongly suggested an infectious process. A stereotactic puncture of the frontal lobe was followed by temporary improvement. A severe progressive left-sided hemiparalysis gave indication for a craniotomy with evacuation of the abscess 9 days later. Culture of aspirated pus yielded growth of a gram-positive, rod-shaped bacterium, later identified as Nocardia otitidiscaviarum by sequencing the 16S rRNA. The patient was treated with meropenem plus rifampicin intravenously for 6 weeks followed by oral ciprofloxacin and rifampicin for 2 months. Due to pharmacokinetic interaction with rifampicin, the prednisolone dose was doubled, and the dose of tacrolimus had to be tripled for maintenance of adequate trough concentrations. Five months following cessation of antibiotic treatment, the patient has regained normal strength and function in her left-sided extremities and has a serum creatinine level of about 160 µmol/l (1.8 mg/dl).
Kidney, Patient and New Millennium Nephrology
Authors: Bonomini Vittorio , Colì Luigi , Scolari Maria P. , Stefoni Sergio , Vangelista Alba
Published: April 2003

The way nephrology develops in the new millennium is bound to be affected by changes in the nephrologist’s clinical environment, as well as by the progress made in basic research which will need to find a clinical application. The nephrologist can expect to be more and more involved in renal substitution therapy, not just providing the treatment, but also managing the cost of the service. In the field of nephropathology, the highest expectations surround molecular biology and its application to both acquired and hereditary renal disease; the goal is to find an outlet for gene therapy in clinical practice. Artificial substitution therapy will focus chiefly on the project of ‘intelligent dialysis’, whereby biological and diagnostic components are combined according the specific needs of the individual patient. The ideal scenario for renal transplantation in the coming millennium would be one where donor supply matches the demand (xenotransplant?), where immunomodulation is perfected, and where diagnoses are based on precise biomolecular events observed in real time.
Increased Rate of Adenine Incorporation into Adenine Nucleotide Pool in Erythrocytes of Patients with Chronic Renal Failure
Authors: Marlewski Maciej , Smolenski Ryszard T. , Szolkiewicz Marek , Aleksandrowicz Zenon , Rutkowski Boleslaw , Swierczynski Julian
Published: April 2003

Background: Elevated purine nucleotide pool (mainly ATP) in erythrocytes of patients with chronic renal failure (CRF) is a known phenomenon, however the mechanism responsible for this abnormality is far from being clear. We hypothesize that the increased rate of adenine incorporation into adenine nucleotide pool is responsible for the elevated level of ATP in uremic erythrocytes. Methods: In chronically uremic patients we evaluated using HPLC technique: (a) plasma adenine concentration; (b) the rate of adenine incorporation into adenine nucleotide pool in uremic erythrocytes. Additionally, the effect of higher than physiological phosphate concentration (2.4 mM) and lower than physiological pH (7.1) on adenine incorporation into erythrocytes adenine nucleotide pool was investigated. Healthy volunteers with normal renal function served as control. Results: The concentration of adenine in plasma of CRF patients was found to be significantly higher than in plasma of healthy subjects. In contrast, adenosine concentration was similar both in healthy humans and in CRF patients. In isolated erythrocytes of uremic patients (incubated in the medium pH 7.4, containing 1.2 mM inorganic phosphate) adenine was incorporated into adenine nucleotide pool at a rate approximately 2-fold higher than in erythrocytes from healthy subjects. The rate of adenosine incorporation into adenine nucleotide pool was similar in erythrocytes of both studied groups. Incubation of erythrocytes obtained from healthy subjects in the medium pH 7.4, containing 2.4 mM inorganic phosphate, caused the increase of adenine incorporation into adenine nucleotide pool by about 60%. Incubation of the cells in the pH 7.1 buffer containing 2.4 mM inorganic phosphate increased the rate of adenine incorporation into adenylate approximately 2-fold as compared to erythrocytes incubated in the medium pH 7.4 containing 1.2 mM inorganic phosphate. Erythrocytes obtained from uremic patients and incubated in the pH 7.1 medium containing 2.4 mM phosphate incorporated adenine into adenine nucleotide pool at a rate similar to erythrocytes incubated in the medium pH 7.4 containing 1.2 mM phosphate. Erythrocytes obtained from either healthy subjects or from patients with CRF and incubated in the presence of higher than physiological concentration of inorganic phosphate (2.4 mM) and lower than physiological pH (7.1) did not exhibit any increase in the rate of adenisine incorporation into adenine nucleotide pool. Conclusion: These results suggest that the increased rate of adenine incorporation into adenine nucleotide pool could be partially responsible for the increased concentration of ATP in uremic erythrocytes.
Lipophilic Antioxidants and Iron Status in ESRD Patients on Hemodialysis
Authors: Lim Paik-Seong , Chan Elsie-C. , Lu Tein-Chung , Yu York Leng , Kuo Shu-Yin , Wang Tsung Hsiu , Wei Yau-Huei
Published: April 2003

Cardiovascular disease remains the major cause of mortality in hemodialysis patients. Abnormal oxidative stress and impaired antioxidant defense may contribute to accelerated atherogenesis associated with uremia. As oxidative modification of lipids appears to be a prerequisite for the development of atherosclerotic lesions, lipophilic antioxidants may be protective. The aim of this study was to determine the plasma levels of lipophilic antioxidants in 82 hemodialysis patients and 30 controls and to investigate the influence of body iron status on the levels of lipophilic antioxidants. The patients were categorized into 3 groups according to their serum ferritin levels. We found that the plasma levels of lycophene, δ-tocopherol, γ-tocopherol and retinol of hemodialysis patients were lower than those of controls. On the other hand, both absolute and lipid-normalized plasma lycophene levels were significantly reduced in those patients in the groups with higher ferritin levels as compared to those with lower ferritin levels. In addition, our study showed that the lipid-normalized plasma levels of β-carotene and α-carotene of hemodialysis patients with higher ferritin levels were lower than those of the patients with lower levels. These data suggest that the plasma levels of lipophilic antioxidants are altered in end-stage renal disease on hemodialysis and may be considered as markers of oxidative stress in these patients. Most importantly, elevated serum ferritin levels may affect the levels of these lipophilic antioxidants.
Hemodialysis Does Not Influence the Peroxidative State Already Present in Uremia
Authors: Hirayama Aki , Nagase Sohji , Gotoh Michihiro , Takemura Katsumi , Tomida Chie , Ueda Atsushi , Aoyagi Kazumasa , Terao Junji , Koyama Akio
Published: April 2003

Hemodialysis (HD) patients are exposed to high oxidative stress, however, the nature of this stress is still unclear. In this study, we employed a specific lipid peroxidative product, phosphatidylcholine hydroperoxide (PCOOH), and evaluated the peroxidative effect of end stage renal disease by measuring thiobarbituric acid reactive substances (TBARS) and PCOOH in both plasma and erythrocyte membrane. We also surveyed plasma TBARS and PCOOH before and after HD sessions thereby assessing oxidative stress by a single HD procedure. The plasma TBARS level of healthy controls was 2.9 ± 0.4 nmol/ml. Those of HD patients before and after HD session were 5.1 ± 1.4 and 3.1 ± 0.5 nmol/ml, respectively, and the pre-HD plasma TBARS levels were significantly higher than those of controls and after HD. The Plasma PCOOH concentration of patients before HD was 119.7 ± 58.4 pmol/ml and was significantly higher than that of controls which was 88.6 ± 14.3 pmol/ml. After HD, the plasma PCOOH level decreased to 103.2 ± 36.0 pmol/ml, which was still significantly higher than that of controls. In erythrocytes, the PCOOH level of patients was 259.3 ± 105.4 nmol/g RBC and was significantly higher than that of controls with 88.6 ± 32.0 nmol/g RBC. Analyzed with respect to the cause of renal disease, the polycystic kidney disease patients showed significantly lower plasma PCOOH levels than the others. These results suggest that there is an increase of lipid peroxidation in both plasma and erythrocytes of HD patients, though this oxidative stress was not brought about by HD.
Serum Concentration of IL-2, IL-6, TNF-Alpha and Their Soluble Receptors in Children on Maintenance Hemodialysis
Authors: Zwolińska Danuta , Medyńska Anna , Szprynger Krystyna , Szczepańska Maria
Published: April 2003

In chronic renal failure patients a state of immunodeficiency paradoxically coexists with the activation of immune effector cells, including monocytes and lymphocytes. The activation of these cells leads to the release of cytokines. The aim of this study was to estimate the serum concentrations of IL-2, IL-6, TNF-α and their soluble receptors: IL-2 sRα, IL-6 sR, sTNF RI in children with chronic renal failure and young adults on maintenance hemodialysis (HD). The study included 16 HD patients (11 females, 5 males) aged 11–22 (mean 16.1 ± 3.1) years and a control group of 15 age-matched healthy children. Only the mean concentration of IL-6 was similar in HD patients and the control group. The levels of the other cytokines were significantly higher in patients undergoing HD compared to the healthy subjects. No significant differences were observed between the pre- and post-dialysis values or between the values obtained using various dialyzer membranes. These data suggest that immune cells in HD children are in an activated state and that neither a single dialysis session nor the type of dialyzer membrane has an influence on the cytokines examined.
Effect of Postural Change on Blood Volume in Long-Term Hemodialysis Patients
Authors: Ookawara Susumu , Suzuki Masayuki , Yahagi Tomoyasu , Saitou Mikio , Tabei Kaoru
Published: April 2003

In healthy subjects, the blood volume (BV) increases rapidly after postural change from standing to the supine position. However, little is known about the effect of postural change on BV in long-term hemodialysis (HD) patients. Therefore, we have examined the BV change caused by adopting the supine position from standing by continuous hematocrit monitoring, using the CRIT-LINE instrument, in 8 anuric HD patients. The hematocrit was monitored for 25 min with the patient in the supine position just before HD. The percentage change in the BV (% Δ BV) was calculated from the hematocrit and approximated using the equation: % Δ BV = b – [1 – exp(–c × time (min)] –a × time (min). Coefficient a was the slope of the linear part in the % Δ BV, b was the magnitude of BV increase and c was the rate of BV increase. Then we examined the relationship between the coefficients (a, b and c) and clinical parameters. In all patients, % Δ BV increased quickly after adopting the supine position. The mean increases were 2.8 ± 0.6% after 5 min and 4.8 ± 0.5% after 25 min. There was a significant correlation between the value of % Δ BV calculated from the hematocrit and the value calculated using above equation (0.92 < r < 0.99, p < 0.001). Although coefficient a did not correlate with a clinical parameter, coefficient b showed a significant positive linear correlation with the serum albumin level (r = 0.816, p < 0.05) and coefficient c showed a significant positive linear correlation with the percentage change in interdialytic weight gain (r = 0.736, p < 0.05). Furthermore, based on the % Δ BV, we calculated the change in total BV, which had increased by 181.5 ± 21.9 ml after 25 min in the supine position. In conclusion, the change in the BV with time by continuous hematocrit monitoring using the CRIT-LINE instrument can be approximated by a modified monoexponential equation. BV increased quickly in HD patients after postural change from standing to the supine position.
Autoantibodies against Oxidized LDL in Chronic Renal Failure: Role of Renal Function, Diet, and Lipids
Authors: Bergesio F. , Monzani G. , Ciuti R. , Cirami C. , Martinelli F. , Salvadori M. , Tosi P.L.
Published: April 2003

Lipid peroxidation (LP) has recently been suggested to trigger the atherosclerotic process as well as to worsen the progression of renal disease. Autoantibodies against oxidized low-density lipoproteins (Ox-LDLAb) were considered to provide a sensitive marker to detect LDL oxidation in vivo. To date few studies have been reported on Ox-LDLAb levels in patients with different degrees of renal failure. The aim of this study was to evaluate the influences of renal function, dietary manipulation, and lipids on Ox-LDLAb concentrations in uremic patients either on conservative or replacement therapy. Seventy-one patients (42 males, 29 females) aged 60 ± 19 years with chronic renal failure (CRF) of different etiology and degree were divided into four groups according to serum creatinine levels [sCr(mg/dl)] and diet: CRF I ≧1.5–3.0, CRF II > 3.0–5.5, and CRF III > 5.5 were all patients on a conventional low-protein diet, while a fourth group included patients on a vegetarian diet supplemented with keto analogues and amino acids (CRF SD >3.0). A further group was represented by patients on dialysis therapy. All patients were examined for Ox-LDLAb, triglycerides (TG), total cholesterol, HDL and LDL cholesterol, and apolipoproteins Apo A1, Apo B, and Lp(a). The results were compared with those of 20 controls (9 males and 11 females) aged 52 ± 11 years with sCr <1.5 mg/dl. Ox-LDLAb increased, although not significantly, with TG and Lp(a) from the early stages of CRF along with the deterioration of renal function. However, TG and Lp(a) levels were significantly higher in all groups of patients except those on vegetarian diet (CRF SD). This group also showed the lowest Ox-LDLAb levels. No relationship was observed between lipids or apolipoproteins and Ox-LDLAb. Hyperlipidemic patients did not show higher Ox-LDLAb levels than normolipidemics. Our results show a progressive increase of LP as the renal function declines, which may account for the increased risk of cardiovascular disease reported in uremia. Dialysis does not correct significantly the oxidative state observed in patients with end-stage renal disease. Vegan diet, by reducing LP, TG, and Lp(a), is supposed to decrease the risk of cardiovascular disease and worth being reconsidered as an alternative effective therapeutic tool in patients with advanced CRF.
Renal Functional Reserve in Patients with Recently Diagnosed Type 2 Diabetes mellitus with and without Microalbuminuria
Authors: Guízar Juan-Manuel , Kornhauser C. , Malacara J.M. , Amador N. , Barrera J.A. , Esparza R.
Published: April 2003

Background/Aims: During the first 10 years, two thirds of the patients with type 2 diabetes mellitus (DM) have microalbuminuria (MA). Functional renal reserve (FRR) and its relationship with proteinuria and metabolic control are unknown at the early phases of disease. We investigated the frequency of MA in recently diagnosed type 2 DM patients, and its association with FRR. Methods: We studied 181 type 2 DM patients with less than 6 months since diagnosis. Renal volume, MA, glomerular filtration rate (GFR) and renal plasma flow (ERPF) were evaluated before and after an acute oral protein load in 28 type 2 DM patients (14 with, and 14 without MA), and in 7 healthy subjects. Results: A total of 10.6% of the patients had MA. MA patients had higher cholesterol and triglyceride levels than those normoalbuminuric. Twenty recently diagnosed type 2 diabetic patients showed high basal GFR. Twelve of them had MA and insulin resistance. After the acute oral protein load, the control subjects and the patients without MA increased their GFR and their ERPF. The group with MA did not. Conclusions: Seventy-five percent of the patients were hyperfiltering. Normoalbuminuric patients had larger increase in GFR and ERRPF than MB patients. We conclude that FRR measurement can be an important tool for the diagnosis of latent diabetic nephropathy.
Intraglomerular Synthesis of Complement C3 and Its Activation Products in IgA Nephropathy
Authors: Abe Katsushige , Miyazaki Masanobu , Koji Takehiko , Furusu Akira , Shioshita Kei , Tsukasaki Shoko , Ozono Yoshiyuki , Harada Takashi , Sakai Hideto , Kohno Shigeru
Published: April 2003

Background: Complement activation is thought to be pathologically important in IgA nephropathy (IgAN). Although C3 deposition in the mesangium is found in IgAN, the origin of C3 is not clear. We recently demonstrated intraglomerular C3 synthesis in the human kidney; however, the activation and pathological role of locally synthesized C3 remains unclear. Here we performed nonradioactive in situ hybridization for C3 mRNA and immunohistochemistry for C3 and its activation products, such as C3d and membrane attack complex (MAC), to determine whether locally produced C3 in glomeruli was activated in IgA nephropathy. Methods: Renal samples from 14 patients with IgAN and 5 with minimal change nephrotic syndrome (MCNS) were examined. Uninvolved portions of surgically removed kidneys with tumors served as normal controls. Results: C3 mRNA was not detected in glomeruli in control tissue and MCNS, but was strongly expressed in resident glomerular cells of IgAN, including mesangial cells, glomerular epithelial cells and the cells of Bowman’s capsule. Examination of serial sections disclosed that more than 70% of cells positive for C3 mRNA were also stained for C3 protein, C3d, and MAC. Double staining for in situ hybridization and immunohistochemistry also revealed that those C3 mRNA signals were present in intraglomerular cells positive for C3. The expression of C3 mRNA and MAC in glomeruli correlated significantly with the degree of mesangial matrix expansion. Conclusions: Our results demonstrated that locally synthesized C3 is activated in the glomeruli of IgAN and that its expression correlated with the severity of mesangial matrix expansion. These findings suggest that activation of C3 may be involved in tissue injury in IgAN through the formation of membrane attack complex.
Polymorphism in Methylenetetrahydrofolate Reductase Gene: Its Impact on Plasma Homocysteine Levels and Carotid Atherosclerosis in ESRD Patients Receiving Hemodialysis
Authors: Lim Paik-Seong , Hung Wan-Ru , Wei Yau-Huei
Published: April 2003

The methylenetetrahydrofolate reductase (MTHFR) gene polymorphism has been shown to be associated with cardiovascular disease in healthy subjects as well as in patients with end-stage renal disease (ESRD). In this study, we examined the allelic frequency and genotype distribution of the MTHFR gene in 151 Chinese ESRD patients receiving hemodialysis and 135 healthy controls. In addition, we investigated the relationship between the MTHFR gene polymorphism and the plasma homocysteine (Hcy) level as well as the intima-media thickness of common carotid artery (CC-IMT) in these patients. The allelic frequency of the MTHFR gene with the C677T mutation in ESRD patients was 24.5% and that in healthy controls was 23%. Mean plasma Hcy level of the ESRD patients (23.1 ± 7.4 µmol/l) was significantly higher than that of the controls (10.1 ± 5.0 µmol/l), but did not correlate with vitamin B6 and vitamin B12 status. Moreover, the extent of hyperhomocysteinemia was genetically affected by the C677T mutation of the MTHFR gene. The plasma Hcy levels for the patients with the CC, CT and TT genotypes of the MTHFR gene were 22.3 ± 6.8, 22.8 ± 7.3, and 28.3 ± 2.8 µmol/l, respectively. In addition, we found that the patients bearing the TT genotype had the highest CC-IMT (0.93 ± 0.07 mm), whereas the lowest values (0.79 ± 0.13 mm) were observed in those who had the CC genotype. One-way ANOVA showed that the CC-IMT in the patients with the TT genotype was significantly greater than that of the patients with the CC genotype (p < 0.05). Moreover, the mean CC-IMT of the patients carrying either TT or CT genotype of the MTHFR gene was significantly higher than that of the patients bearing the CC genotype (0.86 ± 0.14 vs. 0.79 ± 0.13 mm, p = 0.002). Multiple regression analysis, in which the change in CC-IMT was used as the dependent variables, identified age, smoking, the MTHFR genotype (CC = 0, CT = 1, TT = 2) and diabetes mellitus as the independent variables significantly associated with the increase of CC-IMT (p < 0.001). These risk factors jointly explained 43.9% of the CC-IMT variation and age explained most of the variation (R2 = 0.34). We conclude that both the TT genotype and the T allele of the MTHFR gene are associated with the increase of CC-IMT in hemodialysis patients. The C677T mutation of the MTHFR gene may be an independent risk factor that predicts the development of carotid atherosclerosis in ESRD patients.