bluuebunny/crossref_metadata_2025 huggingface dataset:
Effectiveness of Oral L-Arginine in First-Line Treatment of Erectile Dysfunction in a Controlled Crossover Study
Authors: Klotz T. , Mathers M.J. , Braun M. , Bloch W. , Engelmann U.
Published: April 2003

Background and Aims: Relaxation of cavernous smooth muscle is a parasympathetic and non-adrenergic, non-cholinergic mediated process which requires nitric oxide (NO). NO is synthesized from L-arginine by NO synthase (NOS). Some studies report good clinical results under oral L-arginine medication in the treatment of erectile dysfunction. We examined the effectiveness and safety of L-arginine in the treatment of mixed-type impotence. Methods: 32 patients (mean age 51.6 years) with mixed-type impotence diagnosed according to the results of sexual history and urological examination were enrolled in a randomized, placebo-controlled, crossover comparison of an oral placebo with 3 × 500 mg L-arginine/day. A validated questionnaire (KEED) was used to define the grade of impotence with a score. The treatment consisted of two 17-day courses (50 tablets). After a 7-day washout period the patients who initially received the placebo for 17 days were switched to L-arginine and vice versa. We assessed the efficacy with the validated questionnaire at the end of each drug period. Results: 30 patients (94%) completed the whole treatment schedule. Five (17%) patients reported a significant improvement in erectile function at the end of the L-arginine phase and 6 (20%) patients after the placebo period. 17 (56%) patients showed little improvement with L-arginine and 13 (43%) with placebo. In 8 patients (27%) of the verum group there was either no change in the ED score or even a slight worsening. No statistical difference in the impotence scores were found. No drug-related adverse effects occurred with L-arginine treatment. Conclusion: Oral L-arginine 3 × 500 mg/day is not better than placebo as a first-line treatment for mixed-type impotence.
Bilateral Emphysematous Pyelonephritis with Autosomal-Dominant Polycystic Kidney Disease Successfully Treated by Conservative Method
Authors: Shimizu Hirofumi , Hariu Kyouichi , Kamiyama Yutaka , Tomomasa Hiroshi , Iizumi Tatsuo , Yazaki Tsunetada , Umeda Takashi
Published: April 2003

Emphysematous pyelonephritis (EPN) is an uncommon and potentially life-threatening necrotizing inflammation of the renal parenchyma. EPN associated with autosomal dominant polycystic kidney disease (ADPCK) is extremely rare. We report such a case of bilateral EPN with ADPCK that was successfully treated with conservative methods. To our knowledge, our case is only the second to document bilateral EPN occurring with ADPCK and the first one to be treated successfully with conservative methods.
Arg60 Leu Mutation in the First Cytoplasmic Loop of the Platelet Thromboxane A2 Receptor Is Not Essential for Mediating Inhibitory Coupling between the Receptor and Adenylyl Cyclase
Authors: Fuse Ichiro , Higuchi Wataru , Aizawa Yoshifusa
Published: April 2003

Human platelet thromboxane A2 (TXA2) receptor (TXR) has been reported to functionally couple to the inhibitory GTP-binding protein for adenylyl cyclase (Gi). However, it still remains unclear which portions of the TXR structure are critical determinants in that coupling. We have previously reported several patients with platelet dysfunction, whose platelets showed impaired coupling between TXR and phospholipase C caused by an Arg60 to Leu mutation in the first cytoplasmic loop. To investigate whether this portion is essential for mediating inhibitory coupling between TXR and adenylyl cyclase, we analyzed the inhibition by the TXA2 analog of the PGE1 or forskolin-induced platelet cAMP increase in patients’ platelets, and found that the inhibition occurred normally. This suggests that Arg60 in the first cytoplasmic loop of the TXR is not involved in TXR-Gi coupling.
Approaches to Induction Therapy with Adult Acute Myeloid Leukaemia
Authors: Bishop James F.
Published: April 2003

Induction therapy of acute myeloid leukaemia (AML) with standard-dose chemotherapy will result in approximately 64% of patients achieving a complete remission (CR). New drugs which are active in induction therapy in randomised clinical trials are etoposide, idarubicin and high dose cytarabine. Intensification of induction treatment with etoposide or high-dose cytarabine does not appear to alter the CR rate but prolongs remission and has some impact on survival. High-dose cytarabine in induction combinations increase relapse-free survival compared to standard approaches. These induction results appear to parallel results obtained with post-remission therapies intensified with high-dose cytarabine. These studies provide clinical evidence that intensified induction with cytarabine in AML influences subsequent outcome but is more toxic, gives more profound myelosuppression post-remission and has benefit confined to younger patients.
Diagnosis and Monitoring Response to Treatment of Hepatosplenic Candidiasis in Patients with Acute Leukemia Using Magnetic Resonance Imaging
Authors: Sallah Sabah , Semelka Richard , Kelekis Nikolaos , Worawattanakul Suvipapum , Sallah Waddah
Published: April 2003

Hepatosplenic candidiasis (HSC) is a morbid complication encountered in immunocompromised individuals, especially, those being treated with intensive chemotherapy protocols for acute leukemia. Immediate recognition of this complication and initiation of appropriate treatment is crucial in order to control the infection, decrease the morbidity and mortality, and avoid delays in treatment of the underlying condition. The definitive diagnosis requires either positive blood cultures for yeasts in the presence of abnormal findings on imaging studies consistent with HSC, or liver biopsy demonstrating yeast forms or pseudohyphae. We describe our experience in the evaluation of 15 patients with HSC using magnetic resonance imaging (MRI) as a diagnostic and follow-up tool. The diagnosis of HSC was established by liver biopsy in 11 patients (73%), and by positive blood cultures for Candida in 4 patients (27%). All patients had MRI findings consistent with HSC during the study period. Amphotericin B was administered intravenously to all 15 patients (median duration of treatment, 62 days). Repeat MR images were obtained at 2 weeks, 6 weeks and then at monthly intervals until the resolution of abnormalities. The median time for the disappearance of MRI lesions was 9 weeks. Alterations in the appearance of lesions on MRI were noted throughout chemotherapy in all the 13 (86.6%) responding patients. Our results suggest that MRI when used in patients with high clinical suspicion for HSC provide an alternative for liver biopsy or other invasive diagnostic procedures and that appropriate response to treatment can be safely monitored by obtaining sequential MRI studies.
Band 3 Tokyo: Thr837-->Ala837 Substitution in Erythrocyte Band 3 Protein Associated with Spherocytic Hemolysis
Authors: Iwase Satsuki , Ideguchi Hiroshi , Takao Mayumi , Horiguchi-Yamada Junko , Iwasaki Masafumi , Takahara Shinobu , Sekikawa Tetsuaki , Mochizuki Seibu , Yamada Hisashi
Published: April 2003

We report a case of spherocytosis associated with erythrocyte band 3 deficiency. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis of erythrocyte membrane proteins showed that the patient’s band 3 was reduced to about 80% of the control level. Molecular analysis revealed that this quantitative alteration was accompanied by a novel base change at codon 837 (ACG→GCG) of the AE1 gene, resulting in substitution of alanine for threonine. In bone marrow mononuclear cells, both mutant and wild-type mRNA were comparably detected, suggesting that this mutation interfered with band 3 processing or assembly, leading to impaired accumulation of mutant band 3 in the plasma membrane.
Differential Diagnosis of Hb EE and Hb E-β°-Thalassemia by Protein and DNA Analyses
Authors: Wong S.C. , Aw T.C. , Suri R. , Wong C.K. , Plaseska D. , Efremov G.D.
Published: April 2003

DNA analysis was used to confirm the Hb EE genotype and to differentiate from the possible genotype of Hb E-β⁰-thalassemia in two Malay patients. The first patient was a 13-year-old Malay girl, whose parents were available for family studies. The second patient was a 69-year-old Malay woman with no living family members. The presence of Hb E in both propositi was confirmed by: (1) its characteristic electrophoretic mobilities on alkaline/acid gels; (2) its chromatographic properties on anion/cation exchangers, and (3) its mildly insoluble properties. However, differential diagnosis of Hb EE and Hb E-β⁰-thalassemia was challenging in these two cases. In the former, this was because of the possible interactions of the parents’ phenotypes; i.e., the mother had a similar phenotype. In the latter, it was due to the lack of any living family members for family studies. In this communication, we present the protein and DNA analyses, including data on the use of the restriction enzyme Mnl I, for the definitive diagnosis of the Hb EE genotype in the propositi of these two Malay families.
Renal Function in Adult Beta-Thalassemia/Hb E Disease
Authors: Ong-ajyooth Leena , Malasit Prida , Ong-ajyooth Sompong , Fucharoen Suthat , Pootrakul Pensri , Vasuvattakul Somkiat , Siritanaratkul Nopadol , Nilwarangkur Sanga
Published: April 2003

β-Thalassemia hemoglobin E (β-thal/Hb E) is the commonest form of hemoglobinopathy in Thailand. Shortened red cell life span, rapid iron turnover and tissue deposition of excess iron are major factors responsible for functional and physiological abnormalities found in various forms of thalassemia. Increased deposition of iron had been found in renal parenchyma of thalassemic patients, but no systematic study of the effect of the deposits on renal functions has been available. The purpose of this study is to describe the functional abnormalities of the kidney in patients with β-thal/Hb E and provide evidence that increased oxidative stress might be one of the factors responsible for the damage. Urine and serum samples from 95 patients with β-thal/Hb E were studied comparing with 27 age-matched healthy controls. No difference in the creatinine clearance was observed. β-thal/Hb E patients excreted significantly more urinary protein (0.8 ± 0.5 vs. 0.3±0.1 g/day, p < 0.001). Aminoaciduria was found in 16% of the patients. Analysis of urinary protein by SDS-PAGE electrophoresis and silver staining revealed abnormal pattern of protein with increased small molecular weight (<45 kD) bands. Morning urine analysis showed significant lower urine osmolality (578.3 ± 164.6 vs. 762.4 ± 169.9 mosm/kg, p < 0.001) in patients. Patients excreted more NAG (N-acetyl beta-D-glucosaminidase, 26.3 ± 41.3 vs. 8.4 ± 3.9 U/g Cr, p < 0.0001) and β2-microglobulin, 124.3 ± 167 vs. 71 ± 65.5 µg/g Cr, p = 0.001. Plasma and urine MDA (malonyldialdehyde) levels were both raised (p < 0.0001). Nine patients were selected for renal acidification study. All were found to be normal, but showed poor response to DDAVP challenge (urine osmolality 533 ± 71). This is the first report of renal tubular defects found associated with β-thal/Hb E disease. The mechanism leading to the damage is not known but it might be related to increased oxidative stress secondary to tissue deposition of iron, as indicated by the raised levels of serum and urine MDA. It is not known whether these functional defects would have any long-term effects on the patients. Further studies are warranted and means of prevention of these defects should urgently be sought.
Impaired Antioxidant Defense System in the Kidney Tissues from Rabbits Treated with Cyclosporine
Authors: Durak İlker , Karabacak H. İbrahim , Büyükkoçak Serap , Çimen M.Y. Burak , Kaçmaz Murat , Omeroglu Ethem , Öztürk H. Serdar
Published: April 2003

Enzymatic antioxidant defense system and antioxidant defense potential (AOP) were studied in kidney tissue from rabbits treated with cyclosporine (CsA, 25 mg/kg/day), antioxidant vitamins (E, 100 mg/kg/day plus C, 200 mg/kg/day), and CsA plus antioxidant vitamins, and in kidney tissue from control animals. Although no change was observed in superoxide dismutase (SOD) activity, glutathione peroxidase (GSH-Px) and catalase (CAT) activities were found decreased in kidney tissue exposed to CsA for 10 days compared with control tissue. The level of thiobarbituric acid-reagent substances (TBARS) was higher and antioxidant defense potential (AOP) lower in the CsA-treated group compared with the other groups. Histopathological examination reveals important subcellular damage in the renal tissue from the animals treated with CsA. Antioxidant vitamin therapy caused full improvement in the enzyme activities, TBARS levels and AOP, but the subcellular damage was partly ameliorated in the CsA plus vitamin group. Results suggest that CsA impairs the antioxidant defense system and reduces the antioxidant defense potential in the renal tissue. Antioxidant vitamin treatment protects the tissue in part against toxic effects of the drug.
Lessons from 20 Years of Leading a Pediatric Nephrology Program
Authors: Chan James C.M.
Published: April 2003

The patterns of patient referrals, the guidelines for diagnostic procedures and treatment, and the academic leadership have continued to change in the last two decades. The revolution brought about by molecular biology has dramatically changed the pace and direction of medical research during this period. In addition, the introduction of managed care competition in the past decade has dramatically challenged the practice of medicine. The effects of all these changes on nephrology and some lessons learned from developing and leading a regional pediatric nephrology program will be discussed. The role of the National Institutes of Health in changing research focus will be examined. These observations may be useful to those preparing to meet the challenges of clinical care and research in this competitive era.
Low Nitric Oxide Production in Patients with Chronic Renal Failure
Authors: Blum M. , Yachnin T. , Wollman Y. , Chernihovsky T. , Peer G. , Grosskopf I. , Kaplan E. , Silverberg D. , Cabili S. , Iaina A.
Published: April 2003

Background: Rats with chronic renal failure have a low nitric oxide (NO) production and a diminished NO excretion. The supplementation of L-arginine has an inhibitory effect on the progression of renal insufficiency. Methods: The present study was designed to determine whether chronic renal failure patients have a low NO production. Plasma and urine nitrate (NO3) and nitrite (NO2), stable metabolites of NO, were measured in 83 consecutive patients with chronic renal failure. The 83 chronic renal failure patients were divided into three groups: group 1, mild renal failure (creatinine clearance >60 ml/min/1.73 m2); group 2, moderate renal failure (creatinine clearance >30 <60 ml/min/1.73 m2), and group 3, severe renal failure (creatinine clearance <30 ml/min/1.73 m2). Thirty-three healthy volunteers served as controls. Results: The daily urinary NO excretion was significantly lower in patients with moderate and severe renal failure as compared with those with mild renal failure and normal controls. The lowest values were found in the severe renal failure group. When the 24-hour urinary NO excretion or NO per milligram creatinine and the NO clearance were correlated with the renal function in all patients as a group, these parameters were directly correlated with the creatinine clearance and inversely correlated with the serum creatinine level. The plasma NO concentration was not different between the three chronic renal failure groups, but higher than in the controls. Plasma NO in renal failure patients was not correlated with the creatinine clearance or serum creatinine levels. Conclusions: Chronic renal failure is a state of NO deficiency. Treatment strategies to increase NO production (L-arginine supplementation or other NO compounds) may prove to be useful in maintaining the renal function and slow the progression of renal disease.
Improvement of Uremic Autonomic Dysfunction after Renal Transplantation: A Heart Rate Variability Study
Authors: Yildiz A. , Sever M.Ş. , Demirel Ş. , Akkaya V. , Türk S. , Türkmen A. , Ecder T. , Ark E.
Published: April 2003

Autonomic dysfunction in hemodialysis patients is one of the components of uremic neuropathy. In this prospective study, we investigated the effect of renal transplantation on uremic autonomic dysfunction with long-term time-domain and frequency-domain heart rate variability. Fourteen hemodialysis patients (10 male, 4 female; mean age 33 ± 11 (range 16–50) years) were examined before and at the early after transplantation period (mean 4.6 ± 1.5 (range 3–7.5) months). The mean time spent on hemodialysis was 16.7 ± 15.6 (range 6–65) months. In time-domain analysis, significant increases in all parameters except pNN50 (SD, SDANN, SDNN, rMSSD) were observed after renal transplantation (p < 0.01). In frequency-domain analysis, low-frequency (LF) (0.04–0.15 Hz) and high-frequency (HF) (0.15–0.40 Hz) spectral power were found to be significantly increased after renal transplantation (4.54 ± 1.04 vs. 12.58 ± 8.69 for LF (p = 0.005), 2.80 ± 1.0 vs. 6.50 ± 3.55 for HF (p = 0.005)), but the LF/HF ratio was not different from a pretransplant period (1.71 ± 0.349 vs. 1.85 ± 0.49, p = 0.26). It was concluded that autonomic dysfunction in hemodialysis patients is reversible and renal transplantation reverses the sympathetic and parasympathetic autonomic dysfunction simultaneously and at a relatively early stage.
Renoprotective Effects of Captopril in Hypertension Induced by Nitric Oxide Synthase Inhibition in Experimental Nephritis
Authors: Uhlenius Nina , Tikkanen Tuula , Miettinen Aaro , Holthöfer Harry , Törnroth Tom , Eriksson Anders , Fyhrquist Frej , Tikkanen Ilkka
Published: April 2003

Objective: To investigate effects of angiotensin I converting enzyme (ACE) inhibition in experimental nephritis during chronic inhibition of nitric oxide (NO) synthase. Methods: Rats with and without autoimmune Heymann nephritis were treated with a NO synthase inhibitor L-NAME (50 mg/100 ml) and/or an ACE inhibitor captopril (20 mg/100 ml) in drinking water for 12 weeks. Urinary cGMP excretion was used as an indirect measure of NO activity. Blood pressure, urinary albumin, nitrite and nitrate levels, plasma ANP, and plasma renin activity were measured. Kidneys were examined with light microscopy and immunohistochemical methods. Results: Captopril treatment protected rats receiving L-NAME and none of the captopril-treated rats died. Mortality was greatest in the nephritis-L-NAME (57%) and L-NAME (43%) groups. Captopril normalized cGMP excretion, blood pressure, and prevented partly the appearance of albuminuria. Peritubular infiltration of mononuclear cells was clearly enhanced in the nephritis-L-NAME group (found in 80% of the rats) as compared with the nephritis (20%), L-NAME (40%), and control (0%) groups. The peritubular cell infiltration caused by L-NAME was prevented by captopril treatment. L-NAME-induced hypertension was associated with cardiac hypertrophy and this was prevented by captopril. Conclusions: NO may play an important renoprotective role in disease progression of chronic membranous glomerulonephritis. Captopril prevents L-NAME-induced hypertension, improves survival, and ameliorates renal damage in this type of nephritis. Dysfunction of renal NO pathways may be an important factor causing progressive renal damage in chronic nephritis. Our results suggest that the dysfunctional renal NO system may be beneficially activated by ACE inhibitors.
Hydrogen Peroxide Induces Necrosis, Apoptosis, Oncosis and Apoptotic Oncosis of Mouse Terminal Proximal Straight Tubule Cells
Authors: Takeda Michio , Shirato Isao , Kobayashi Mami , Endou Hitoshi
Published: April 2003

Hydrogen peroxide (H2O2) has been shown to be an important mediator of ischemic and toxic tubular damage. The purpose of this study was to identify the mode of cell death observed in H2O2-exposed cultures of mouse terminal proximal straight tubule (S3) cells. H2O2 induced a dose- and time-dependent decrease in viability of S3 cells. Morphologically, S3 cells exposed to H2O2 (0.05–0.1 mM) showed features of necrosis, apoptosis, oncosis and apoptotic oncosis, whereas necrosis occurred most frequently in every experimental condition tested. On the other hand, agarose gel electrophoresis of DNA extracted from S3 cells exposed to H2O2 revealed a typical DNA ladder pattern. These data suggest that H2O2-induced proximal tubule damages are associated with the induction of various modes of cell death including necrosis, apoptosis, oncosis and apoptotic oncosis, and with the activation of endonuclease.
Antiglomerular Basement Membrane Antibody-Mediated Glomerulonephritis after Intranasal Cocaine Use
Authors: Peces Ramón , Navascués Rafael A. , Baltar José , Seco Miguel , Alvarez Jaime
Published: April 2003

We report a case of rapidly progressive glomerulonephritis due to antiglomerular basement membrane (anti-GBM) antibodies that progressed to end-stage renal disease in a 35-year-old man who used intranasal cocaine on an occasional basis. In contrast to many prior reports of acute renal failure occurring with cocaine-associated rhabdomyolysis, this patient did not have any evidence of acute muscle damage and myoglobin release. Circulating anti-GBM antibodies and renal biopsy with linear IgG and C3 deposits confirmed the diagnosis of anti-GBM disease. The possibility of anti-GBM must be considered in the differential diagnosis of acute renal failure in cocaine addicts. This unusual combination raises complex questions regarding the pathogenesis of this type of renal injury.
Assessment of Occlusion of the Vascular Access in Patients on Chronic Hemodialysis: Comparison of Physical Examination with Continuous-Wave Doppler Ultrasound
Authors: Migliacci Rino , Selli Maria Laura , Falcinelli Francesca , Vandelli Lorenza , Lusvarghi Egidio , Santucci Antonella , Nenci Giuseppe G. , Gresele Paolo
Published: April 2003

Background: Dialysis access occlusion is the most common cause of hospitalization and a frequent indirect cause of mortality in patients on chronic hemodialysis. The clinical assessment of an arteriovenous shunt is presently the most widely adopted method for the diagnosis of vascular access occlusion in hemodialysis patients, but no studies have yet investigated objectively its sensitivity and positive predictive value (PPV). Continuous-wave (CW) Doppler ultrasound is a simple, inexpensive, and noninvasive technique for the assessment of arterial blood flow. We have carried out a prospective evaluation of the PPV of CW Doppler for the diagnosis of vascular access occlusion in hemodialysis patients and compared it with clinical investigation. Methods: Fourty-one hemodialysis patients with clinical diagnosis of occlusion of their fistula were studied, and in 23 of them the diagnosis of occlusion was objectively validated. Results: CW Doppler in the patients in whom occlusion was objectively validated showed PPV of 86 and 83% under basal conditions and after fistula compression, respectively, with sensitivities of 95 and 100%, respectively. Clinical diagnosis, under the same conditions, showed a PPV of 83% and a sensitivity of 100%. Conclusions: CW Doppler and clinical examination have a similar high sensitivity for the diagnosis of occlusion of the dialysis access; thus, there is no need to use routinely Doppler CW examination, unless objective documentation is required.
Relationship between Polymorphism in the Angiotensinogen, Angiotensin-Converting Enzyme or Angiotensin II Receptor and Renal Progression in Japanese NIDDM Patients
Authors: Tomino Yasuhiko , Makita Yuichiro , Shike Toshihide , Gohda Tomohito , Haneda Masakazu , Kikkawa Ryuichi , Watanabe Tsuyoshi , Baba Tsuneharu , Yoshida Hiroaki
Published: April 2003

We determined the relationship between the gene polymorphism of angiotensinogen (AGT), angiotensin-converting enzyme (ACE), or angiotensin II receptor (AT1R) and the progression of diabetic nephropathy in a multicenter trial of ethnically homogeneous Japanese patients with non-insulin-dependent diabetes (NIDDM). Gene polymorphism of ACE I/D, AGT M235T and AT1R A1166C was determined by polymerase chain reaction amplification using allele-specific primers. Japanese NIDDM patients (n = 1,152) were selected from several diabetic clinics. All patients were divided into three groups as follows: (1) group I (n = 407): normoalbuminuric patients; (2) group II (n = 327): microalbuminuric patients, and (3) group III (n = 418): overt albuminuric patients. Clinical factors for investigation in all patients were the date of birth, gender, levels of urinary albumin excretion, findings of the ocular fundus, duration of diabetes, hemoglobin A1c and blood pressure. It appears that genetic polymorphisms in the renin-angiotensin systems, i.e. ACE or AT1R, may affect the progression to renal failure of patients (especially females) with NIDDM.
Quality of Life in End-Stage Renal Disease Patients after Successful Kidney Transplantation: Development of the ESRD Symptom Checklist – Transplantation Module
Authors: Franke Gabriele Helga , Reimer Jens , Kohnle Mathias , Luetkes Peter , Maehner Nicole , Heemann Uwe
Published: April 2003

The End-Stage Renal Disease Symptom Checklist – Transplantation Module (ESRD-SCL®) was developed to assess the specific physical and psychological quality of life of renal transplant recipients, with a special focus on side effects of immune system suppression therapy. A list of potentially relevant items was administered to 458 transplant recipients. The symptoms present in >20% of patients were chosen, and factor analysis was used to create the final questionnaire which consists of 43 items in six dimensions: (1) limited physical capacity (10 items; internal consistency: Cronbach’s α = 0.85); (2) limited cognitive capacity (8 items, α = 0.82); (3) cardiac and renal dysfunction (7 items, α = 0.76); (4) side effects of corticosteroids (5 items, α = 0.77); (5) increased growth of gum and hair (5 items, α = 0.78), and (6) transplantation-associated psychological distress (8 items, α = 0.80). All questions are scored on a five-point Likert scale. Validity was demonstrated in correlation with corresponding SF-36 scales and in a stepwise hierarchical regression model predicting the subscales of the ESRD-SCL by sociodemographic and medical data. The ESRD-SCL was found to have adequate reliability, test-retest correlations in a subsample of 88 stable patients after 1 year, and construct validity.
Anticardiolipin Antibodies in Acute Poststreptococcal Glomerulonephritis and Streptococcal Impetigo
Authors: Ardiles Leopoldo , Ramirez Pablo , Moya Patricia , Caorsi Italo , Mezzano Sergio
Published: April 2003

Anticardiolipin (aCL) antibodies have been described in diverse clinical situations, linked to the risk of thrombosis in different vascular locations. They have been rarely studied in renal diseases, and occasionally they have been associated with glomerular thrombosis. We analyzed the incidence of aCL (isotypes IgG, IgA, and IgM) in samples, taken during the acute phase of the disease, from 27 well-documented patients having acute poststreptococcal glomerulonephritis. Twelve cases were positive on IgG testing, 1 case on IgA testing only, and no one was positive on IgM testing. A serological follow-up was performed with a second sample taken about 7 months later, for the patients initially positive on IgG testing showing persistence in 9. Clinical variables during the acute phase and after a follow-up period of 25 (range 6–89) months were analyzed for possible associations with the presence of these antibodies, but non was significantly related. Renal histopathological investigation did not reveal particular findings in the aCL-positive patients, and glomerular thrombosis was not found in any case. In addition, serum samples from 12 streptococcal impetigo patients without renal involvement were analyzed, showing similar incidence (4 positive on IgG testing, 1 of them positive on IgM testing as well, and no one positive on IgA testing) and titers of aCL antibodies. We conclude that the presence of aCL antibodies in acute poststreptococcal glomerulonephritis may be a marginal immunological phenomenon unrelated to the glomerular disease, triggered by the streptococcal infection.
Time Course of Cytokine mRNA Expression in Kidneys of Rats with Unilateral Ureteral Obstruction
Authors: Sommer Manfred , Eismann Ulrike , Deuther-Conrad Winnie , Wendt Thoralf , Mohorn Thomas , Fünfstück Reinhard , Stein Günter
Published: April 2003

The development of renal interstitial fibrosis (RIF) is related to the expression and excretion of cytokines and growth factors. Thus, we investigated the time course of mRNA expression of cytokines known as causative factors in a model of RIF in rats before and on day 10 after unilateral ureteral obstruction (UUO), when first signs of fibrosis were visible, as well as during progressive RIF. UUO causes a fivefold increase in mRNA expression of monocyte chemoattractant protein 1 15 days after surgery as compared with contralateral kidneys. The level remains elevated about three-fold up to day 25. The mRNA of the fibrogenic cytokine transforming growth factor beta 1 (TGF-β1) is increased two- to threefold during the time course, whereas the mRNAs of platelet-derived growth factor B chain (PDGF-B) and its receptor beta (PDGF-Rβ) increase after UUO, reaching their maxima on days 10–15. PDGF-B mRNA increase up to day 15, marking the onset of fibrosis, and decreases thereafter, whereas the expression of the PDGF-Rβ mRNA remains elevated more than threefold over the entire study period. Incubation of cultured renal fibroblasts with TGF-β1 and/or PDGF-B suggests that their specific action on cell growth and proliferation is maintained even when they are used in combination. The sustained elevation of TGF-β1 and PDGF-B/PDGF-Rβ mRNA levels confirms the assumption of a particular involvement of these cytokines in the pathogenesis of RIF. The mRNA expression of the gap junctional protein connexin 43 in ureteral ligated kidneys is increased sixfold already 5 days after UUO. In this way, the increased connexin 43 mRNA levels indicate a possible function in the remodeling of the kidney tissue after tubular damage and fibrosis.
Alterations of Arterial Function in End-Stage Renal Disease
Authors: London Gérard M.
Published: April 2003

Cardiovascular disease is a major cause of morbidity and mortality in patients with end-stage renal disease (ESRD). Epidemiological and clinical studies have shown that this is most frequently related to damage of large conduit arteries. Macrovascular disease develops rapidly in uremic patients and is responsible for the high incidence of ischemic heart disease, sudden death, peripheral artery diseases, and congestive heart failure. The most frequent causes of these complications are occlusive lesions due to atherosclerosis. Nevertheless, atherosclerosis, a disease characterized by the presence of plaques, represents only one form of structural response to metabolic and hemodynamic alterations which interfere with the process of aging, i.e., arteriosclerosis, characterized by dilation/hypertrophy and stiffening of arteries. The vascular complications in ESRD are ascribed to two different but associated mechanisms, namely atherosclerosis and arteriosclerosis. Whereas the former principally affects the conduit function with ischemic lesions being the most characteristic consequence, the latter primarily disturbs the cushioning function of large arteries. Arteriosclerosis in ESRD patients is characterized by diffuse dilation and hypertrophy of large conduit arteries and stiffening of arterial walls and represents a clinical form of accelerated aging process. The main clinical characteristics of arterial stiffening concern changes in blood pressure with isolated increase in systolic pressure and normal or lower diastolic pressure. The consequences of these alterations are: (1) an increased left ventricular afterload with development of left ventricular hypertrophy and increased myocardial oxygen demand and (2) altered coronary perfusion and subendocardial blood flow distribution. Epidemiological studies have identified arterial remodeling and stiffening as independent predictors of overall and cardiac mortality in ESRD patients.
Urinary N-Acetyl-β-D-Glucosaminidase and Neopterin Aid in the Diagnosis of Rejection and Acute Tubular Necrosis in Initially Nonfunctioning Kidney Grafts
Authors: Kotanko Peter , Margreiter Raimund , Pfaller Walter
Published: April 2003

Aim: The study aimed at investigating urinary neopterin, a marker of cellular immune response, and urinary N-acetyl-β-D-glucosaminidase (NAG), a marker of tubular damage, as noninvasive means to differentiate between acute tubular necrosis (ATN) and rejection in initially nonfunctioning (INF) human renal transplants. Methods: Seventy-two renal transplant patients were studied. Forty-five of them experienced an uncomplicated early posttransplant course, 27 patients suffered from INF. Twenty-two patients experienced ATN, 5 patients had a total of six biopsy-proven rejections. The NAG activity was measured by a colorimetric assay, neopterin by high-performance liquid chromatography. Receiver operating characteristics (ROC) analysis was applied to compute diagnostic performance and an optimal discriminating threshold. Results: Demographic characteristics (age, gender, cold and warm ischemia periods, HLA mismatches) and posttransplant urinary NAG and neopterin excretions did not differ between ATN and rejection groups. Both urinary NAG and neopterin excretions were lower in the control group (NAG 1.8 ± 1.0 U/mmol urinary creatinine; neopterin 270 ± 126 nmol/mmol urinary creatinine; mean ± SD) as compared with the ATN group (NAG 12 ± 10 U/mmol, p < 0.001 vs. control group; neopterin 303 ± 195 nmol/mmol, n.s.) and the rejection group (NAG 7 ± 8 U/mmol, p < 0.01; neopterin 508 ± 419 nmol/mmol, p < 0.01). The ratio of urinary neopterin to NAG excretion (uNNR; dimension nmol neopterin/U NAG activity) increased during rejections as compared with ATN (139 ± 74 vs. 50 ± 38 nmol/U, p < 0.01). The area under the ROC curve for uNNR was 0.88 ± 0.07 (p < 0.001). Applying a ROC-estimated optimal discriminator of uNNR (80 nmol/U), 16 patients with ATN and all six rejection episodes were classified correctly. Conclusion: The uNNR provides a noninvasive means to aid in the differential diagnosis of rejection and ATN in INF human renal transplants.
Dimensions of Arteriovenous Fistulas in Patients with Autosomal Dominant Polycystic Kidney Disease
Authors: Hadimeri Henrik , Hadimeri Ursula , Attman Per-Ola , Nyberg Gudrun
Published: April 2003

Background/Aim: Aneurysms are known manifestations of autosomal dominant polycystic kidney disease (ADPKD). We investigated whether the dimensions of arteriovenous fistulas created for performance of haemodialysis were affected by the original disease. Methods: The lumen diameter of the fistula was studied by ultrasound in 19 patients with ADPKD and in 19 control patients. The patients’ sex, age, the duration of their fistulas, haemoglobin values and blood pressure levels were similar in both groups. The monitoring was performed along the forearm part of the vein, and the maximal diameter was measured. The diameters at the two needle insertion sites were also measured. Results: The ADPKD patients had a significantly higher fistula diameter than the control patients: 12 (range 8–19) mm versus 8 (range 6–24) mm at the widest level (p = 0.003). There were no significant differences in the diameters at the needle insertion sites. Conclusion: The receiving veins of arteriovenous fistulas in patients with ADPKD have an abnormality that causes a greater than normal dilatation in response to the arterialization. We postulate that this phenomenon is linked with the increased prevalence of aneurysms in ADPKD.
Decreased Bilirubin-Binding Capacity in Uremic Serum Caused by an Accumulation of Furan Dicarboxylic Acid
Authors: Tsutsumi Yasuhiro , Maruyama Toru , Takadate Akira , Shimada Hidekata , Otagiri Masaki
Published: April 2003

In chronic renal failure, substances that are effectively excreted in healthy subjects accumulate in serum. These substances, uremic toxins, include a variety of organic acids. It has been reported that a decrease in the bilirubin (BR) binding capacity occurs in the serum of renal failure patients. 3-Carboxy-4-methyl-5-propyl-2-furanpropanoic acid (CMPF) has a high affinity for human serum albumin (HSA) and is a potent inhibitor of the serum protein binding of many drugs. We recently reported that CMPF and BR share the binding site for dicarboxylate molecules on the HSA molecule [Pharm Res 1999;16:916–923]. In this study, in order to confirm whether CMPF is involved in the decrease of BR serum binding capacity in chronic renal failure patients, the total concentrations of uremic toxins, CMPF, and indoxyl sulfate (IS) and the free BR concentration in serum from healthy volunteers and renal failure patients were determined. Both total CMPF and IS concentrations correlate with the free BR concentration. However, results from the peroxidase method reveal that IS cannot displace BR under the physiological condition [IS]/[HSA] <1. We, therefore, conclude that CMPF is one of the substances which contribute to the decreased binding capacity of BR in uremic serum.
Usefulness of a Highly Sensitive Urinary and Serum IL-6 Assay in Patients with Diabetic Nephropathy
Authors: Shikano Masahiko , Sobajima Hiroshi , Yoshikawa Hiroto , Toba Takako , Kushimoto Hiroko , Katsumata Hideki , Tomita Makoto , Kawashima Shirou
Published: April 2003

Background/Aim: Interleukin-6 (IL-6) promotes the growth of renal mesangial cells. IL-6 may play a major role in such mesangial proliferation, but there has been little research on IL-6 in relation to diabetic nephropathy because of the difficulty in measuring urinary and serum IL-6 levels. Using a newly developed, highly sensitive IL-6 assay, we studied the relationship between serum and urinary IL-6 and diabetic nephropathy. Methods: We investigated 72 patients with type 2 diabetes. Urinary and serum IL-6 concentrations were measured using a chemiluminescent enzyme immunoassay with a detection limit of 0.11 pg/ml. Results: There was a significant increase of the serum IL-6 level as diabetic nephropathy progressed, with the level being 1.4 ± 0.3 pg/ml in patients with normal albuminuria, rising to 2.4 ± 0.6 pg/ml in patients with microalbuminuria and then to 4.4 ± 0.8 pg/ml in those having proteinuria. The serum IL-6 level was also significantly correlated with fibrinogen and aortic pulse wave velocity. The urinary IL-6 level was also significantly increased in diabetic patients as nephropathy progressed. Both serum and urinary IL-6 levels were high in the group with nephropathy, but there was no correlation between the two. Conclusion: The urinary IL-6 level seems to be a good indicator of diabetic nephropathy, and atherosclerotic changes were related to the serum IL-6 level. The serum IL-6 may, therefore, be useful in the evaluation of atherosclerosis including nephropathy.
Increased Excretions of β2-Microglobulin, IL-6, and IL-8 and Decreased Excretion of Tamm-Horsfall Glycoprotein in Urine of Patients with Active Lupus nephritis
Authors: Tsai Chang-Youh , Wu Tsai-Hung , Yu Chia-Li , Lu Jia-Yu , Tsai Ying-Yang
Published: April 2003

Tubulointerstitial nephritis is a less frequently recognized but important complication of systemic lupus erythematosus. We have investigated the cytokine β2-microglobulin (β2M) and Tamm-Horsfall glycoprotein (THG) excretions in the urine of systemic lupus erythematosus patients to identify indices for evaluation of tubulointerstitial inflammation in lupus nephritis (LN). Daily urine was collected from 15 patients with active LN, from 12 patients with inactive LN, and from 17 normal subjects. The amounts of soluble interleukin (IL) 2 receptor, IL-6, IL-8, β2M, and THG in urine were measured. β2M and THG were regarded as indicators of proximal and distal renal tubule function, respectively. The urinary excretions of IL-6 and IL-8 were significantly higher in patients with active LN than in those with inactive LN and in normal individuals. The excretion of soluble IL-2 receptor in all three groups of subjects was not significantly different. On the other hand, the excretion of β2M in patients with LN was significantly higher than that in normal individuals. The excretion of β2M in patients with active or inactive LN was not significantly different. The THG excretion was lower in patients with active LN and tubulointerstitial inflammation as compared with patients with inactive LN or normal individuals. Six patients underwent pulse cyclophosphamide therapy during the course of experiments. Five of them showed a decrease in IL-8 and IL-6 excretions in urine after the treatment. The excretions of β2M and THG in urine, in addition to IL-6 and IL-8, can reflect the renal inflammatory activity in patients with lupus tubulointerstitial nephritis as well as in those having lupus glomerulonephritis.
Adequate Seroresponse to Influenza Vaccination in Dialysis Patients
Authors: Antonen Jaakko A. , Hannula Päivi M. , Pyhälä Reijo , Saha Heikki H.T. , Ala-Houhala Ilpo O. , Pasternack Amos I.
Published: April 2003

Background: Hemodialysis (HD) patients are immunocompromised, and they have been shown to react suboptimally to recommended vaccinations. Advances in dialysis therapy and other supportive measures may theoretically result in better immune system functions. Clinical evidence supporting this theory has, however, not been presented. With influenza vaccination response, we tried to address this question. Methods: 42 HD and 15 continuous ambulatory peritoneal dialysis (CAPD) patients were vaccinated with a trivalent influenza vaccine, and the seroresponses at 5 weeks were measured. The results were compared with those of similarly vaccinated 20 nephrology outpatient clinic patients with varying degrees of renal insufficiency and those of 31 cardiac patients with normal renal function. Results: The dialysis patients had higher prevaccination titers of hemagglutination-inhibiting (HI) antibodies to all three vaccine virus antigens than the other groups due to more frequent previous vaccinations. The dialysis patients exhibited lower antibody increases, but an almost comparable proportion of them reached a protective antibody level (HI titers ≧40) 5 weeks after vaccination [A/H3N2: 61% (cardiac patients), 35% (nephrology outpatient clinic patients), 67% (CAPD), and 36% (HD); A/H1N1: 71, 70, 80 and 60; B: 97, 90, 80, and 76%, respectively]. Among the HD group, all patients receiving parenteral calcitriol except 1 (83%), but only 50% of the other HD patients produced protective antibody titers at least to two out of three vaccine virus antigens. No other patient- or HD treatment-associated parameter was significantly related to the vaccination-induced antibody response. Conclusions: We conclude that influenza vaccination of dialysis patients according to current recommendations may be effective. Additionally, our results suggest that parenteral calcitriol treatment may augment the immune response of HD patients even in a clinically relevant way, an effect so far shown only in in vitro studies.
Complement-Mediated Killing of Mesangial Cells in Experimental Glomerulonephritis: Cell Death by a Combination of Apoptosis and Necrosis
Authors: Shimizu Akira , Masuda Yukinari , Kitamura Hiroshi , Ishizaki Masamichi , Ohashi Ryuji , Sugisaki Yuichi , Yamanaka Nobuaki
Published: April 2003

Immune system mediated, particularly antibody- and complement-mediated, glomerular injury triggers glomerulonephritis (GN). To characterize complement-mediated cytotoxicity in GN, we assessed the process of mesangial cell death induced by C5b-9 attack in Thy-1 GN. Cell injury was recognized morphologically, and nuclear DNA breaks were confirmed by the DNA nick end labeling (TUNEL) method as well as DNA gel electrophoresis. Thy-1 GN was induced in rats with anti-Thy-1.1 antibody injection. Mouse IgG (administered antibody) and rat C3 were detected in all glomeruli within 5 min after antibody injection. Damaged mesangial cells with condensed as well as TUNEL-positive nuclei could be observed at 20 min and became prominent at 40–60 min. Ultrastructurally, damaged mesangial cells contained condensed apoptotic nuclei from 40 to 60 min, whereas the cytoplasm showed necrotic degeneration. This was followed by progressive lysis of both nuclei and cytoplasm. The DNA ‘ladder’ pattern was observed by gel electrophoresis of extracted DNA between 40 and 60 min and correlated with the increased number of TUNEL-positive damaged mesangial cells. To examine the role of complement in this form of cell death, complement depletion was induced in rats by cobra venom factor. Complement-depleted rats showed no rat C3 deposition, rare TUNEL-positive mesangial cells, rare ultrastructural degenerated mesangial cells with apoptotic nuclei and necrotic cytoplasm, and no DNA ‘ladder’ pattern on gel electrophoresis at 40 min, although prominent mouse IgG was seen in glomeruli. To analyze milder forms of complement injury, a low dose of the antibody was administered to rats with a normal complement level. A few TUNEL-positive mesangial cells were detected in the glomeruli which contained apoptotic nuclei and necrotic cytoplasm. Our results indicate that an apoptotic death mechanism accompanies cell necrosis in complement-mediated mesangial cell destruction in GN and that this unusual form of cell death may represent a combination of apoptosis-necrosis within the same cell. Complement injury activates a ‘death program’ which in turn leads to irreversible damage of mesangial cells and which may contribute to initiation and development of GN.
Improvement of Renal Function in Patients with Chronic Gout after Proper Control of Hyperuricemia and Gouty Bouts
Authors: Perez-Ruiz Fernando , Calabozo Marcelo , Herrero-Beites Ana María , García-Erauskin Gorka , Pijoan Jose Ignacio
Published: April 2003

Aim: To evaluate the effect of nonsteroidal anti-inflammatory drug (NSAID) withdrawal on renal function in patients with chronic gout after proper control of hyperuricemia and gouty symptoms. Methods: Patients with chronic gout, who regularly used NSAIDs to control gouty symptoms prior to urate-lowering therapy, were prospectively followed up in an observational study. Risk factors for renal function impairment were recorded, and the clearance of creatinine (Ccr) was initially measured while on colchinine therapy to prevent gouty bouts. Therapy with urate-lowering drugs was started in order to keep serum urate levels under 6.0 mg/dl (275 µmol/l), and the Ccr was monitored during the follow-up period. Final assessment of the renal function was made after 1 year free from gouty bouts and without NSAID therapy during this period. Results: 87 patients completed a 1-year period of NSAID withdrawal. Low initial Ccr was related to age, hypertension, hypertriglyceridemia and the presence of previous renal diseases. After proper control of gout and NSAID withdrawal during 1 year, the mean Ccr significantly raised from 94 to 104 ml/min. The improvement was especially significant in patients whose initial Ccr was under 80 ml/min. Their mean Ccr rose from 60 to 78 ml/min, and 12 of 29 patients achieved normal Ccr at the end of the study. No risk factor correlated with improvement of the renal function. Conclusions: Renal function impairment in patients with chronic gout is mainly related to vascular risk factors, but improvement of the renal function was observed after proper control of hyperuricemia and NSAID withdrawal. Optimal control of hyperuricemia and, therefore, of symptoms of gout should be especially considered in patients with vascular risk factors in order to avoid renal function loss due to NSAID use.