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Abstract

T.J. Stephenson, K.D.R. Setchell, C.W.C. Kendall, D.J.A. Jenkins, J.W. Anderson and P. Fanti

¹Division of Nutritional Science, College of Agriculture, University of Kentucky, ²Department of Internal Medicine, Division of Nephrology, Bone and Mineral Metabolism, College of Medicine, University of Kentucky Medical Center, ³Department of Internal Medicine, Division of Endocrinology and Molecular Medicine, College of Medicine, University of Kentucky Medical Center, Lexington, KY, ⁴Clinical Mass Spectrometry, Cincinnati Children’s Hospital Medical Center, Cincinnati, OH, USA, and ⁵Clinical Nutrition and Risk Factor Modification Center, St. Michael’s Hospital, University of Toronto, Toronto, Ontario, Canada
Background: Diabetic nephropathy is the most frequent cause of end-stage renal disease in the Western world. Dietary intake, including protein amount and type, seems to affect the progression of renal disease. This pilot study tested the hypothesis that substituting soy protein for animal protein in the diets of diabetics would help correct glomerular hyperfiltration. Methods: Twelve young adults (aged 29.9 ± 2.4 years) with type 1 diabetes mellitus (duration of diabetes 15.1 ± 2.3 years) and hyperfiltration (glomerular filtration rate, GFR > 120 ml/min/1.73 m2) completed a crossover, dietary intervention trial. After a four-week assessment of baseline characteristics and dietary habits, subjects were assigned to either a control or soy diet for eight weeks after which each subject was crossed over to the alternative diet for another eight-week period. Results: Mean GFR was significantly reduced (p < 0.02) after eight weeks on the soy diet (143 ± 7.4 ml/min/1.73 m2) compared with baseline (159 ± 7.7 ml/min/1.73 m2) and control diets (161 ± 10.0 ml/min/1.73 m2). Urinary excretion of the soy isoflavones was significantly higher (p < 0.01) at the end of the soy diet (genistein 1,014.6 ± 274.1 nmol/h, daidzein 2,645.1 ± 989.6 nmol/h) compared with baseline (genistein 53.7 ± 31.1 nmol/h, daidzein 151.1 ± 74.1 nmol/h) and control diets (genistein 41.1 ± 13.3 nmol/h, daidzein 127.5 ± 54.0 nmol/h). The soy diet significantly reduced total and LDL cholesterol by 7% and 9%, respectively. Conclusions: Implementation of a soy-based diet appears to reduce the GFR and total and LDL cholesterol of young adults with type 1diabetes and glomerular hyperfiltration, thus affecting positively their clinical profile.Correspondence to:
Dr. P. Fanti

Division of Nephrology - MC 7882

University of Texa

Health Science Center at San Antonio

7703, Floyd Curl Drive

San Antonio, TX 78229, USA
Email: fanti@uthscsa.edu

Abstract

M. Yenicesu, M.I. Yilmaz, K. Caglar, A. Sonmez, T. Eyileten, T. Kir, C. Acikel, N. Bingol, Y. Oguz, T.A. Ikizler and A. Vural

Department of ¹Nephrology, ²Internal Medicine, ³Epidemiology, Gülhane School of Medicine, Etlik-Ankara, ⁴Department of Biochemistry, Bayindir Medical Center, Ankara, Turkey, and ⁵Department of Nephrology, Vanderbilt University Medical Center, Nashville, TN, USA
Aims: Adiponectin seems to be an important modulator for metabolic and vascular diseases. We aimed to measure plasma adiponectin levels in type 2 diabetic patients and investigate any association with the severity of proteinuria. Methods: 80 patients (mean age, 46.9 ± 5.1 years; body mass index (BMI), 25.8 ± 1.98 kg/m2) and 47 healthy volunteers (mean age, 46.1 ± 5.5 years; BMI 26.74 ± 2.23 kg/m2) were included. Plasma adiponectin concentration, insulin levels, homeostasis model assessment (HOMA) indices, calculated glomerular filtration rate (GFR), high sensitive C reactive protein (hsCRP) and biochemistry panel were determined in all subjects. The association between adiponectin concentration and proteinuria was evaluated. Additionally, the relationship between adiponectin and hsCRP and calculated GFR were also investigated. Results: Adiponectin levels in patients were significantly lower than those of controls (n = 80; 8.76 ± 4.50 µg/ml for patients, n = 47; 24.27 ± 5.59 µg/ml for controls, p < 0.001). Plasma adiponectin levels in patients with proteinuria were significantly lower than those without proteinuria (n = 43; 6.81 ± 2.82 µg/ml for proteinuria, n = 37; 11.98 ± 3.32 µg/ml for no proteinuria, p < 0.001). There was a significant negative correlation between plasma adiponectin concentrations and the degree of proteinuria (r = –0.433, p < 0.001). There were also significant negative correlations between adiponectin concentrations and insulin levels as well as HOMA index in the patient group (r = –0.322, p = 0.004; r = –0.301, p = 0.032). Additionally there was a significant negative correlation between adiponectin and hsCRP levels in the patient group (r = –0.872, p < 0.001). Conclusion: The results show that adiponectin is lower in patients with type 2 diabetes and the levels are negatively correlated with the severity of proteinuria.Correspondence to:
M.I. Yilmaz, MD
Specialist in Nephrology
Department of Nephrology
Gülhane School of Medicine
06018 Etlik-Ankara, Turkey
Email: mahmutiyilmaz@yahoo.com

Abstract

S.R.S. Sprovieri, Y.A. Sens and D. Martini Filho

¹Department of Medicine and ²Department of Pathology, Santa Casa de São Paulo Faculty of Medical Sciences, São Paulo, Brazil
Aims: The pathogenesis of lupus nephritis (LN) has not been fully understood. The renin-angiotensin system (RAS) is implicated in various immunological and non-immunological phenomena, and the polymorphism of the RAS genes has been associated with cardiovascular and renal disease onset and outcome. Therefore, we evaluated the possible association between the polymorphism of the renin-angiotensin system genes and the development of the different types of histological lesions of lupus nephritis in Brazilian patients. Methods: 72 LN patients and 65 healthy subjects (sex-and ethnic-matched) were enrolled and compared in this study. Following the extraction of genomic DNA from the leukocytes of the peripheral blood, the genotypes of the angiotensin converting enzyme (ACE I/D), of the angiotensinogen (AGT M235T) and of the angiotensin II type 1 receptor (AGTR1 A1166C) were determined by the polymerase chain reaction. The renal lesions of the patients with LN were classified by the histological findings according to the WHO criteria. In addition, the activity and chronicity indices were used to assess the severity of renal involvement. Results: Among the 72 patients with LN, there were 17 class II, 8 class III, 40 class IV and 7 class V, according to the WHO criteria. Individuals with the III and IV classes of LN (WHO) showed a significantly increased DD genotype frequency of ACE I/D genes when compared to the control group (48% vs. 27.7%, c2 = 4.885, df = 1, p = 0.0442). No difference was found in the distribution of the AGT M235T and AGTR1 A1166C genotype frequencies among the LN of the different histological classes (WHO) and healthy controls. There was no association between genetic polymorphism of ACE, AGT M235T and AGTR1 A1166C and susceptibility to lupus nephritis, nor histological activity and chronicity indices in renal biopsy among the patients studied. Conclusions: This study suggests that the DD genotype of the ACE may be associated with the development of the more severe histological forms of lupus nephritis.Correspondence to:
S.R. Schwarzwälder Sprovieri
Diretoria Clínica
Santa Casa de São Paulo Central Hospital
Rua Dr. Cesário Motta Júnior 112
Vila Buarque, São Paulo, SP, Brazil
Email: luvieri@uol.com.br

Abstract

W. Yumura, S. Suganuma, K. Uchida, T. Moriyama, S. Otsubo, T. Takei, M. Naito, M. Koike, K. Nitta and H. Nihei

Department of Medicine, Kidney Center, Tokyo Women’s Medical University, Tokyo, Japan
Aim: Mizoribine (MZR) is a purine antimetabolic immunosuppressant agent that has few little severe adverse events. We studied whether maintenance therapy with MZR and prednisolone (PSL) in severe proliferative lupus nephritis patients could improve immunity, reduce proteinuria, prevent renal relapse, and reduce steroid dose. Method: Long-term maintenance therapy with MZR and PSL was evaluated in ten patients with biopsy-proven proliferative lupus nephritis. Patients with severe lupus nephritis, who had proteinuria of 0.5 g or more even after treatments with plasma exchange and/or pulse methyl prednisolone, were recruited. MZR at an average dose of 140 ± 10 (100 – 200) mg was administered two to three times/day in combination with PSL. The average period for the MZR maintenance therapy was 89.7 ± 5.5 (70 – 126) months. Urine protein excretion, serum hemolytic complement activity (CH50), C3, serum creatinine, general and biochemical blood examinations, anti-ds-DNA antibody were collected at each monthly medical examination. Results: All patients were females, mean age 43.0 ± 3.3 years. A significant decrease in proteinuria was noted two years after the combination therapy (p = 0.0016). Five patients experienced lupus nephritis relapse. Patients who did not experience relapses had their MZR combination therapy initiated earlier (p = 0.037) when compared with the patients who experienced relapses. Serum creatinine levels remained unchanged in all patients throughout treatment and follow-up, even during renal relapses. Levels of C3 and CH50 normalized as proteinuria decreased. None of the patients developed serious side effects during MZR treatment. A significant steroid-sparing effect was observed three years after initiating MZR (p = 0.0025). Conclusion: From our long-term observation, maintenance therapy with low-dose PSL combined with MZR can eliminate proteinuria and have steroid-sparing effect. Early initiation of the therapy can protect against renal relapses among severe proliferative lupus nephritis patients without serious side effects.Correspondence to:
W. Yumura, MD
Department of Medicine
Tokyo Women’s Medical University
8-1 Kawata-cho
Shinjuku-ku, Tokyo, 162-8666, Japan
Email: yumura@kc.twmu.ac.jp

Abstract

Y. Yang, K. Ohta, M. Shimizu, A. Nakai, Y. Kasahara, A. Yachie and S. Koizumi

¹Department of Pediatrics, Graduate School of Medical Science, and ²Department of Laboratory Sciences, School of Health Sciences, Faculty of Medicine, Kanazawa University, Kanazawa, Ishikawa, Japan
Aim: IgA nephropathy associated with heavy proteinuria is considered a more progressive form of this disease. In this report, we describe the favorable clinical effect of combination therapy with low doses of an angiotensin-converting enzyme inhibitor (ACEI) and angiotensin II receptor blocker (ARB) in the chronic stage of pediatric IgA nephropathy associated with heavy proteinuria. Patients: We initially used ACEI for seven children with IgA nephropathy and heavy proteinuria who did not achieve remission with the routine treatment including steroids. Results: With ACEI therapy alone, only three patients showed an antiproteinuric response. In one of the three patients, the proteinuria decreased by half, but was still over 1 g/day. In the other four patients, the proteinuria did not decrease. In these five patients, of whom one partial was a responder and four were non-responders for ACEI, ARB was added, and in marked contrast to ACEI therapy alone, the antiproteinuric effect was significantly augmented (p < 0.01). The antiproteinuric response induced by combination therapy was not accompanied by blood pressure changes. Urinary low-molecular protein and N-acetyl-b-D-glucosaminidase (NAG) levels tended to decrease after both ACEI alone and combination therapy. Conclusion: These data indicate that inhibition therapy of the angiotensin system not only decreases proteinuria levels but also protects renal tubular cells. Moreover, there were no obvious side effects associated with this therapy during the follow-up period of our clinical trial. In conclusion, this report shows that the combination of low doses of ACEI and ARB might provide marked antiproteinuric and long-term renoprotective effects in pediatric IgA nephropathy, with this approach appearing to be both well-tolerated and safe.
Correspondence to:
Dr. K. Ohta Department of Pediatrics Graduate School of Medical Science Kanazawa University 13-1 Takaramachi Kanazawa, Ishikawa 920-8641, Japan
Email: kohta@ped.m.kanazawa-u.ac.jp

Abstract

S. Herget-Rosenthal, F. Pietruck, L. Volbracht, T. Philipp and A. Kribben

¹Department of Nephrology, and ²Department of Clinical Chemistry,
University Hospital, Essen, University Duisburg-Essen, Germany
Aims: Acute renal failure (ARF), defined by a rapid decrease of glomerular filtration rate (GFR), is associated with high mortality. Early and accurate detection of decreasing GFR is critical to prevent the progression of ARF and to potentially improve its outcome. Serum creatinine, the conventional GFR marker, has major limitations. We prospectively evaluated whether serum cystatin C detected a rapid GFR decrease earlier and more accurately than serum creatinine. Methods: In ten patients undergoing nephrectomy for living related kidney transplantation, serum creatinine and cystatin C were determined daily. The decrease of GFR was quantitated preoperatively by creatinine clearance and MAG3 scintigraphy. The GFR decrease was defined by a 50 –100% increase of cystatin C or creatinine from preoperative values. Ten patients without renal impairment served as controls. Results: Initially, patients had a creatinine clearance of 105 ± 14 ml/min/1.73 m2. Due to nephrectomy, patients lost 45 ± 3% of their renal function. Serum cystatin C significantly increased already one, serum creatinine two days after nephrectomy. Cystatin C demonstrated an increase by 50 – 100% 1.4 ± 0.9 days earlier than creatinine (p = 0.009). Serum cystatin C performed well detecting the GFR decrease with higher diagnostic values compared to creatinine. This was indicated by a sensitivity of 50, 70 and 80% of cystatin C to detect the GFR decrease on the three days following nephrectomy. Conclusions: Serum cystatin C detects rapid GFR decreases one to two days earlier than creatinine. Cystatin C is an early and accurate marker to detect rapid GFR decreases as in ARF.Correspondence to:
Dr. S. Herget-Rosenthal
Klinik für Nieren- und Hochdruckkrankheiten
Universitätsklinikum Essen
Hufelandstraße 55
45122 Essen, Germany
Email: stefan.herget-rosenthal@uni-essen.de

Abstract

Y. Takahashi, A. Sano and M. Matsuo

Departments of ¹Pediatrics, ²Radiology and ³MR Center, Tenri Hospital, Nara, Japan
Aims: The nutcracker phenomenon (NCP) is the significant compression of the left renal vein (LRV) by the aorta and superior mesenteric artery (SMA), and found in the patients with so-called idiopathic renal bleeding, orthostatic proteinuria and severe orthostatic intolerance. The purpose of this study is to investigate clinical implications among these disorders possibly related to the NCP. Material and methods: We analyzed 93 pediatric patients (56 with idiopathic renal bleeding, 14 with massive orthostatic proteinuria and 23 with severe orthostatic intolerance), and the findings of 64 patients were compared on both digital subtraction angiography (DSA) and ultrasonography (US) to obtain a new US classification of the NCP with seven grades. Results: US grades of the NCP were well-correlated with DSA findings (rs = 0.797, p < 0.0001). LRV stenosis was a typical finding in patients with idiopathic renal bleeding. LRV occlusion was observed in 70% for severe orthostatic intolerance, and in contrast in 18% and 14% for idiopathic renal bleeding and massive orthostatic proteinuria, respectively. Collateral veins on color Doppler US as well as a mirror image of the SMA in the aorta on conventional US were found as subsidiary signs of LRV occlusion. Extreme dilatation of the LRV was present in 44% for massive orthostatic proteinuria and in 7% for idiopathic renal bleeding (p < 0.0001). Conclusions: A new US classification is useful for the diagnosis of the NCP in diverse clinical symptoms.Correspondence to:
Dr. Y. Takahashi Department of Pediatrics Tenri Hospital Mishima-cho 200 Tenri 632-8552, Nara, Japan
Email: t-taisei@tenriyorozu-hp.or.jp

Abstract

K. Shalansky and J. Jastrzebski

¹Pharmaceutical Sciences CSU, Vancouver General Hospital, Faculty of Pharmaceutical Sciences, and ²Division of Nephrology, Vancouver General Hospital, Faculty of Medicine, University of British Columbia, Vancouver, BC, Canada
Aims: In March 2003, our hemodialysis unit switched all patients from subcutaneous (s.c.) rHuEPO to intravenous (i.v.) darbepoetin. The primary outcome was to assess the efficacy of i.v. darbepoetin to maintain target serum hemoglobin (Hb) compared to s.c. rHuEPO. Secondary outcomes were to evaluate the manufacturer’s recommend guidelines for conversion of rHuEPO to darbepoetin, and to assess the cost implications of darbepoetin therapy. Methods: This was an 18-month open-label observational study of 95 hemodialysis patients. At the time of the switch to darbepoetin (baseline), data were collected retrospectively for six months and prospectively for 12 months, at three-month intervals. The first six months of darbepoetin therapy was considered a dose titration phase, thus, data were analyzed comparing two six-month periods: (–) six months to baseline (rHuEPO phase) and (+) 6 – 12 months (darbepoetin phase). Doses were titrated to a target Hb of 120 – 135 g/l. Results: There was no significant difference in Hb between phases at any time point. Mean Hb ranged from 119.6 – 121.5 g/l for rHuEPO and 121.9 – 123.4 g/l for darbepoetin. The median darbepoetin dose remained stable throughout the analysis at 30 mg/week while the median dose of rHuEPO rose from 8,000 U/week at minus six months to 9,000 U/week at baseline. Median 12-month cost savings associated with the administration of darbepoetin were estimated at $ 212,000. The recommended darbepoetin dose from the manufacturer’s conversion table was deemed too low for baseline rHuEPO doses above 17,000 U/week. A more simplified dose conversion nomogram was created. Conclusion: Darbepoetin was able to maintain similar serum Hb levels compared to rHuEPO at a substantially reduced cost.Correspondence to:
Dr. K. Shalansky
Pharmaceutical Sciences CSU
Vancouver General Hospital
855 W12th Ave,
Vancouver, BC V5Z 1M9, Canada
Email: karen.shalansky@vch.ca

Abstract

J.J. Kazama, K. Omori, N. Takahashi, Y. Ito, H. Maruyama, I. Narita, F. Gejyo, Y. Iwasaki and M. Fukagawa

¹Division of Clinical Nephrology and Rheumatology, Niigata University Graduate School of Medical and Dental Sciences, Niigata, ²Oita University of Nursing and Health Science, Hazama, Oita, and ³Kidney and Dialysis Center, Kobe University Hospital, Kobe, Hyogo, Japan
Background: Osteoprotegerin is a natural glycoprotein which plays a critical role in osteoclast physiology. Elevated levels of circulating osteoprotegerin may account for the development of bone and mineral metabolic abnormalities in uremia. Little is known about the effects of vitamin D therapy on the circulating osteoprotegerin levels in dialysis patients. Patients and methods: Fifty chronic dialysis patients whose plasma intact PTH levels were greater than 300 pg/ml were analyzed for the study. Following a four-week washout time during which all vitamin D administration was halted, 10 mg of maxacalcitol was intravenously injected thrice a week. Results: The circulating intact PTH, bone-specific alkaline phosphatase and intact osteocalcin levels were significantly lowered, while the serum calcium levels were elevated after the therapy. The osteoprotegerin levels significantly decreased after the therapy (p < 0.0001). Conclusion: Maxacalcitol therapy reduced the circulating osteoprotegerin levels and improved secondary hyperparathyroidism. The observed effects were the opposite of those expected from previous in vitro studies. Osteoprotegerin may mediate and/or modify the effect of active vitamin D therapy in dialysis patients.Correspondence to:
Dr. J.J. Kazama
Division of Clinical Nephrology and Rheumatology
Niigata University
Graduate School of Medical and Dental Sciences
1-754 Asahimachi-Dori
Niigata, Niigata 951-8510 Japan
Email: jjkaz@med.niigata-u.ac.jp

Abstract

M. Tanaka, K. Itoh, K. Matsushita, K. Matsushita, H. Fujii and M. Fukagawa

¹Department of Nephrology, Akebono Clinic, Kumamoto, and ²Division of Nephrology and Dialysis Center, Kobe University Graduate School of Medicine, Kobe, Japan
The conventional intact-PTH assay detects both (1-84)-PTH and C-terminal fragments. The newer PTH assays, bio-intact-PTH assay and whole-PTH assay, use an antibody that binds only if the first amino acid is present, making it specific for the complete molecule, (1-84)-PTH. Thus, the intact-PTH concentrations are theoretically higher than bio-intact-PTH concentrations, and the ratio of bio-intact-PTH/intact-PTH is usually less than 1. These findings are observed in normal subjects and patients with primary and secondary hyperparathyroidism. Here we present a hemodialysis patient with severe secondary hyperparathyroidism who was found to have abnormally higher plasma bio-intact-PTH concentrations than intact-PTH concentrations, and the abnormally high bio-intact-PTH/intact-PTH ratio improved after parathyroidectomy (PTx). The patient was a 67-year-old man on maintenance hemodialysis since 1995. Since 2003, he was found to have high plasma intact-PTH concentrations and two swollen parathyroid glands in the neck. PTx with forearm autograft was performed in October 2003. Before PTx, an abnormally high ratio of bio-intact-PTH/intact-PTH was detected (840 pg/ml/770 pg/ml, > 1), while the same ratio was improved to normal range (100 pg/ml/200 pg/ml, < 1). Recently, a few patients with parathyroid carcinoma have been found to have higher (1-84)-PTH concentrations than intact-PTH concentrations with abnormally high (1-84)-PTH/intact-PTH ratio. Moreover, a new molecular form of PTH distinct from (1-84)-PTH was detected in these patients. We speculate that the resected parathyroid gland in our patient might have produced a new molecular form of PTH that was less well detected by the conventional intact-PTH assay.Correspondence to:
M. Tanaka, MD, PhD Department of Nephrology Akebono Clinic, 5-1-1 Shirafuji, Kumamoto 861-4112, Japan
Email: tanaka@matusita-kai.or.jp

Abstract

O. Lambotte¹, A. Dürbach², R. Kotb¹, S. Ferlicot³, J.F. Delfraissy¹ and C. Goujard¹

¹Department of Internal Medicine, ²Department of Nephrology, and
³Department of Pathology, CHU Bicêtre AP-HP, Le Kremlin Bicêtre, France
The autoantibodies secreted by B lymphocytes have recently been shown to play an important role in autoimmune disease. B lymphocyte depletion by rituximab, a monoclonal anti-CD20 antibody, has been introduced for the treatment of several autoimmune disorders. Few reports have underlined its potential use for the treatment of systemic lupus erythematosus (SLE). We report here the occurrence of extracapillary glomerulonephritis associated with a thrombotic event shortly after rituximab treatment for a lupus flare-up in a patient with anticardiolipin antibodies. This observation suggests that rituximab alone may be insufficient to control severe SLE with glomerulonephritis and should therefore be used with caution in patients with this condition.
Correspondence to:
Dr. O. Lambotte
Department of Internal Medicine
CHU de Bicêtre
78 rue du Général Leclerc
94275, Le Kremlin Bicêtre, Cedex, France
Email: olivier.lambotte@bct.ap-hop-paris.fr

Abstract

K.T. Woo, K.S. Wong, Y.M. Chin, Y.K. Lau and G.S.C. Chiang

Abstract

H. Yamabe, N. Nakamura, M. Nakamura, M. Shimada, R. Kumasaka and S. Tsunoda

Abstract

S. Sanada, O. Hotta, M.Sato and Y. Taguma

Abstract

S.K. Bowry and U. Kuchinke-Kiehn

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Volume 64, No. 1/2005(July)