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Abstract

N. Ieiri, O. Hotta and Y. Taguma

Department of Nephrology, Sendai Shakaihoken Hospital, Sendai, Miyagi, Japan
Background: Acute glomerulonephritis (AGN) is a rare complication of human parvovirus B19 (HPB19) infection. The clinical and pathological features of AGN associated with HPB19 (HPBAGN) have not yet been fully elucidated. Methods: We analyzed 10 HPBAGN cases, focusing on their clinical and serological features. We also performed histopathological examinations of renal biopsy specimens obtained from three of the 10 patients on day 15, 19 and 23, respectively, after the onset of symptoms. The phenotype of the glomerular infiltrating leukocytes in HPBAGN was determined by immunohistochemical staining and compared with that of glomerular infiltrating leukocytes in poststreptococcal AGN (PSAGN) and lupus nephritis. Results: The clinical course and laboratory data of the HPBAGN patients revealed female preponderance (male = 0, female = 10), erythema in 9 of the 10 patients, leukopenia in 3, positive antinuclear antibody titer in 4, hypocomplementemia with low levels of C3, C4, and CH50 in 9, and liver dysfunction in 7. Endocapillary hypercellularity of leukocytes was demonstrated in all three patients who underwent renal biopsy. In comparison with PSAGN and lupus nephritis with crescents there were less neutrophil in HPBAGN compared to marked macrophage infiltrates that were equally intense in both the control and the HPBAGN group. Conclusions: Our findings indicate that HPBAGN is characterized by female preponderance, erythema, leukopenia, positive antinuclear antibody titer, and hypocomplementemia, and that minor neutrophil infiltration may be related to mild clinical manifestations despite the marked fixation of glomerular leukocytes in HPBAGN.Correspondence to:
N. Ieiri, MD Department of Nephrology Sendai Shakaihoken Hospital Tsutsumimachi 3-16-1 Aoba-ku, Sendai, Miyagi, 981-8501, Japan
Email: no-ieiri@pf6.so-net.ne.jp

Abstract

T. Nakahata, H. Tanaka, K. Tsugawa, M. Kudo, K. Suzuki, E. Ito and S. Waga

¹Department of Pediatrics, Hirosaki University School of Medicine and ²National Aomori Hospital, Hirosaki, Japan
Aim: It has been reported that the pharmacokinetics of cyclosporin A (CsA) in children is different from that in adults. It appears that, in general, pediatric patients metabolize CsA more rapidly than adult patients, necessitating the use of higher dose of the drug in pediatric transplant recipients. In this context, we speculated that single-dose daily administration of low-dose CsA may be associated with a higher peak blood level without associated trough blood level elevation, and thereby yield better results and allow safer use of the drug than the conventional twice daily administration dosing used for the treatment of childhood idiopathic nephrotic syndrome (INS). Methods: A total of 10 children with steroid-dependent relapsing INS (9 with biopsy-proven minimal-change disease) who showed steroid toxicity were enrolled in the study. The initial daily dose of CsA (Neoral) used was around 2.0 mg/kg, given as a single daily dose before breakfast. The dose was subsequently adjusted to achieve a C1-C2 point blood level between 600 – 800 ng/ml. The dose of the concomitantly administered prednisolone was tapered following the commencement of CsA. Results: The mean daily CsA dosage, the mean C1-C2 point blood level and the mean trough blood level in the subjects were 2.2 ± 0.8 mg/kg, 754.0 ± 71.9 ng/ml and 42.7 ± 29.2 ng/ml, respectively. At the latest observation, after a mean duration of 17 months (6 – 24 months) of CsA therapy, the minimum dose of prednisolone required for maintenance of clinical remission and the calculated relapse rate were significantly decreased as compared to the respective pretreatment values (0.52 ± 0.46 mg/kg on alternate days, vs. 0.97 ± 0.63 mg/kg on alternate days, and 0.28 ± 0.32 times per six months, vs. 1.06 ± 0.41 times per six months, respectively, p = 0.005). No significant change was observed in the mean estimated GFR value as compared to the pretreatment value (183.1 ± 35.4 ml/min/1.73 m2 vs. 185.4 ± 39.3 ml/min/1.73 m2). No evidence of CsA nephrotoxicity was observed in a repeat renal biopsy performed around 12 months after the commencement of CsA therapy in two patients. Conclusions: Despite the limitations of the study, our results suggest that administration of low-dose CsA as a single daily dose with C1-C2 point blood level monitoring might be an equally effective and safe and, therefore, more cost-beneficial, protocol for the treatment of steroid-dependent cases of relapsing INS, as conventional twice-daily administration of CsA with trough blood level monitoring. Further studies to confirm the long-term efficacy and safety of this CsA treatment protocol in larger numbers of patients are, however, needed.Correspondence to:
H. Tanaka, MD
Department of Pediatrics
Hirosaki University School of Medicine
5 Zaifu-cho, Hirosaki 036-8562, Japan
Email: hirotana@cc.hirosaki-u.ac.jp

Abstract

W. Richmond, G. Colgan, S. Simon, M. Stuart-Hilgenfeld, N. Wilson and U.S. Alon

¹Section of Nephrology and ²Department of Medical Research, Children’s Mercy Hospital, University of Missouri, Kansas City, MO, USA
Background: Random urine Ca/creatinine (UCa/Cr) is used to estimate 24-hour Ca excretion. However, due to decreased urine creatinine excretion in children with decreased muscle mass (DMM), UCa/Cr overestimates their Ca excretion. Objective: To evaluate whether in children with DMM random urine Ca/osmolality (UCa/Osm) can accurately predict hypercalciuria (24-hour urine Ca > 4.0 mg/kg) and at which “cutoff” value. Methods: 19 children with DMM and 29 with normal muscle mass (NMM), ages 6 – 17 years, were studied. DMM was diagnosed based on clinical findings and decreased serum creatinine, and confirmed by low urine creatinine excretion. Over 24 hours, subjects collected each void separately. After each sample was analyzed, samples of each participant were combined to form a 24-hour specimen from which an aliquot (AL) was obtained; 24-hour urine Ca was first correlated with the corresponding AL Ca/Cr and Ca/Osm. As an internal control, a similar assessment of proteinuria was conducted. In the next step, AL data were compared with individual urine samples to identify the time of day when a random sample best correlates with AL. Results: The correlation coefficient between 24-hour Ca and AL Ca/Cr in all children was 0.61, in NMM 0.96, and in DMM 0.69 (in all p < 0.001). The correlation coefficient between 24-hour urine Ca and AL Ca/Osm in all children was 0.90, in NMM 0.90, and in DMM 0.91 (in all p < 0.001). In children with DMM, the correlation coefficient of 24-hour protein with AL protein/Cr was 0.75, and with protein/Osm 0.98 (both p < 0.001). Receiver operating characteristic curves showed UCa/Cr as a better predictor of 24-hour Ca > 4.0 mg/kg in NMM, whereas UCa/Osm was a better predictor of hypercalciuria in DMM patients. In NMM, UCa/Cr ratio > 0.20 had sensitivity of 88% and specificity of 96% in detecting 24-hour Ca > 4.0 mg/kg, whereas in those with DMM UCa/Osm (× 10) ratio of > 0.25 had sensitivity of 100% and specificity of 93% in detecting hypercalciuria. It was further found that random urine specimens collected between 9:00 a.m. and 2:00 p.m. best represented 24-hour urine data. Conclusion: In children with DMM, UCa/Osm can successfully replace UCa/Cr as a screening tool for hypercalciuria.Correspondence to:
U.S. Alon, MD
Section of Nephrology
Children’s Mercy Hospital
2401 Gillham Road
Kansas City, MO 64108, USA
Email: ualon@cmh.edu

Abstract

R. Garcia-Naveiro¹, A. Rodriguez-Carmona¹ and M. Pérez-Fontán¹,²

¹Division of Nephrology, Hospital Juan Canalejo, A Coruña, Spain, and ²Department of Medicine, University of A Coruña, Spain
Background: Estimations of glomerular filtration rate (GFR) obtained either by the modification of diet in renal disease study equation (MDRD-GFR) or by classic 24-hour urine collection-based methods (mean of creatinine and urea clearance (Ccr-ur)) are considered to be equivalent in patients with chronic renal failure (CRF). However, the agreement between both methods has been insufficiently studied in patients during the most advanced stages of CRF. Methods: We compared 615 estimations of GFR performed by both methods simultaneously in adult (> 18 years) patients with advanced (aCRF) (15 – 30 ml/min/1.73m2) and preterminal (tCRF) (< 15 ml/min/1.73m2) chronic renal failure. We also analyzed the influence of some relevant covariables (demographic characteristics, inflammatory and nutritional markers) with respect to the concordance between both methods. Results: In aCRF, mean GFR were 19.7 ± 5.5 (MDRD-GFR) and 19.3 ± 3.7 ml/min/1.73m2 (Ccr-ur) (mean difference 0.4 ml/min/1.73m2, 95% confidence interval CI –0.3/1.1, p = 0.26), with an intraclass correlation coefficient of 0.46. In tCRF, mean GFR was 12.5 ± 4.2 and 10.4 ± 2.7 ml/min/1.73m2, respectively (mean difference 2.1 ml/min/1.73m2, 95% CI 1.7/2.4, p < 0.0005), with an intraclass correlation coefficient of 0.43. Multivariate analysis identified lean body mass, body mass index, protein nitrogen appearance, proteinuria, gender, age, albumin (aCRF) and prealbumin (tCRF) as variables independently correlated with the difference MDRD-GFR minus Ccr-ur. Lean body mass was by far the strongest predictor of deviations between both methods, both in aCRF (R2 = 0.66, p < 0.0005) and tCRF (R2 = 0.49, p < 0.0005). Conclusions: MDRD-GFR and Ccr-ur show an acceptable agreement in advanced stages of chronic renal failure. However, MDRD-GFR produces estimations of GFR systematically higher than those given by the Ccr-ur method, in patients with tCRF. Moreover, this overestimation is particularly marked in some high risk subsets, including elderly patients and those presenting markers of a poor nutritional condition. Until this issue is further clarified, GFR should be estimated using Ccr-ur rather than MDRD-GFR in patients with tCRF, as also in older and malnourished patients with aCRF, as this may represent a more conservative and safer approach at the time of planning initiation of renal replacement therapy.Correspondence to:
Dr. M. Pérez Fontán
Division of Nephrology
Hospital Juan Canalejo
Xubias 84
15006 A Coruña, Spain
Email: mfontan@canalejo.org

Abstract

M. Tanaka, T. Ohashi, M. Kobayashi, Y. Eto, N. Miyamura, K. Nishida, E. Araki, K. Itoh, K. Matsu-shita, M. Hara, K. Kuwahara, T. Nakano, N. Yasumoto, H. Nonoguchi and K. Tomita

¹Department of Nephrology, Akebono Clinic, Kumamoto, ²Department of Gene Therapy, Institute of DNA Medicine, The Jikei University School of Medicine, Tokyo, ³Department of Metabolic Medicine, Kumamoto University School of Medicine, Kumamoto, ⁴Hara Medical Clinic, Kumamoto, ⁵Kuwahara Medical Clinic, Kumamoto, ⁶Nakano Medical Clinic, Kumamoto, ⁷Yasumoto Medical Clinic, Kumamoto, and ⁸Department of Nephrology, Kumamoto University Graduate School of Medical Sciences, Kumamoto, Japan
Background: Although previous studies reported that the prevalence of Fabry’s disease was 0.16 – 1.2% in hemodialysis (HD) patients based on measurement of a-galactosidase A (a-Gal A) activity, few reports detected female patients by the screening for a-Gal A. Here we determined the prevalence of Fabry’s disease not only in male but also in female HD patients by measuring a-Gal A. Methods: Plasma a-Gal A was measured in 696 consecutive males (n = 401) and females (n = 295) on HD. Patients with low plasma a-Gal A were examined for leukocyte a-Gal A, and patients with low leukocyte a-Gal A underwent a-Gal A gene sequence analysis for possible mutations, and family survey. Results: Among 15 patients with low plasma a-Gal A activity, 4 male patients with low leukocyte a-Gal A and 1 female patient revealing low plasma a-Gal A were detected in 696 HD patients (0.7% of total patients). 3 of these 5 patients were already diagnosed to have the classical type of Fabry’s disease. The other 2 patients were newly diagnosed as Fabry’s disease, and did not have typical manifestations of Fabry’s disease other than renal failure and left ventricular hypertrophy. DNA analysis of these 2 newly diagnosed patients revealed that each had an a-Gal missense mutation, previously identified (E66Q, M296I). Conclusion: Fabry’s disease should be considered in the etiology of unexplained end-stage renal disease. Not only affected males but also affected females undergoing HD patients can be readily diagnosed by a-Gal A activities and gene analysis. These patients and their family members may benefit from enzyme replacement therapy for Fabry’s disease.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

I. Mucsi¹,²,³, C. Almási¹, G. Deák¹,², A. Marton¹, C. Ambrus¹,², K. Berta², P. Lakatos¹, A. Szabó⁴ and C. Horváth¹

¹¹st Department of Internal Medicine, Semmelweis University Budapest, Hungary, ²Semmelweis University – Fresenius Medical Care Dialysis Center, Budapest, Hungary, ³Division of Nephrology, Faculty of Medicine, University of Toronto, Humber River Regional Hospital, Toronto, Ontario, Canada and ⁴¹st Department of Pediatrics, Semmelweis University Budapest, Hungary
Aims: An increasing amount of evidence suggests that 25-hydroxy vitamin D3 (25(OH)D3) may contribute to the bone health of patients with chronic kidney disease (CKD). The underlying vitamin D status of these patients, however, has often been neglected. In a cross-sectional study we assessed the association between vitamin D status and parathyroid function, bone turnover, bone mass and structure in patients on maintenance hemodialysis. Methods: 69 patients on maintenance hemodialysis were assessed by bone densitometry (DEXA) and quantitative bone ultrasound (QUS). Serum 25-hydroxy vitamin D3 levels, serum markers of bone turnover and clinical data were tabulated. Results: A high prevalence of potentially significant vitamin D3 deficiency was found in this patient group: 59% of the patients had a 25(OH)D3 level below 20 nmol/l. There was a significant negative correlation between serum 25(OH)D3 levels and serum intact parathyroid hormone (iPTH) (r = –0.231, p < 0.05), and this association remained significant after controlling for potential co-variables. Furthermore, we show here that serum 25(OH)D3 concentration is positively correlated with bone mineral density (BMD) measured at the radius (r = 0.424, p < 0.01). Finally, we show for the first time that 25(OH)D3 levels are significantly and independently correlated with broadband ultrasound attenuation (b = 0.262, p < 0.05) measured with calcaneal quantitative bone ultrasound (QUS) in patients with chronic renal failure. Conclusion: Vitamin D3 deficiency may contribute to the impaired bone health of patients on maintenance dialysis.Correspondence to:
Dr. I. Mucsi, M.D., Ph.D.
Division of Nephrology
Humber River Regional Hospital
200 Church Street
Toronto, Ontario, M9N 1N8, Canada
Email: mucsist@net.sote.hu

Abstract

M. Iyoda, K. Matsumoto, T. Hato, A. Kuroki, T. Shibata, K. Kitazawa and T. Sugisaki

Department of Nephrology, School of Medicine, Showa University, Tokyo, Japan
Herein we describe a case of a patient with elderly-onset systemic lupus erythematosus presenting as acute renal failure due to disseminated intravascular coagulation. A 78-year-old man was admitted to our hospital with fever and generalized lymphadenopathy. He was diagnosed as having systemic lupus erythematosus on the basis of renal involvement, hematological abnormality and positivity for antinuclear and anti-double-stranded DNA antibodies. Renal biopsy revealed lupus nephritis (class III and V (A/C)) with focal glomerular thrombosis. He responded to hemodialysis and corticosteroid therapy with remission of serological values and renal function. Possible mechanisms underlying the coexistence of these conditions are discussed.Correspondence to:
M. Iyoda, MD Department of Nephrology Showa University School of Medicine 1-5-8 Hatanodai Shinagawa-ku, Tokyo 142-8666, Japan
Email: iyoda@med.showa-u.ac.jp

Abstract

C.-S. Chang, A.-H. Yang and C.-H. Chang

¹Division of Nephrology, Department of Internal Medicine, Shin Kong Wu Ho-Su Memorial Hospital, Taipei, ²Department of Pathology and Laboratory Medicine Taipei Veterans General Hospital, Taipei, and ³School of Medicine, Fu Jen Catholic University, Tipei County, Taiwan
The duration of diabetes mellitus and presence of hyperglycemia appear to be important in the development of diabetic nephropathy. Here, we present three patients with edema, heavy proteinuria, chronic renal failure, in whom no past or present symptomatic glucose intolerance or diabetic retinopathy were found. The kidney biopsy of these patients showed diffuse glomerular basement membrane thickening and nodular glomerulosclerosis, which resembled diabetic nephropathy. The renal function of these patients deteriorated rapidly and renal replacement therapy started later in the average of 11 months since the first visiting. These cases were diagnosed as diabetic nodular glomerulosclerosis, although there was no obvious evidence for diabetes. The absence of overt diabetes and diabetic retinopathy at presentation of nodular glomerulosclerosis in these cases does not refute the hypothesis that metabolic consequence of hyperglycemia is a prerequisite for the pathogenesis of diabetic microangiopathy, but some factors other than hyperglycemia may be responsible for renal damage in our patients. The modifiable risk factors in such a condition are postulated and discussed.Correspondence to:
Dr. C.-H. Chang
Division of Nephrology
Department of Internal Medicine
Shin Kong Wu Ho-Su Memorial Hospital
95 Wen-Chan Road, Shih-Lin district
Taipei, Taiwan
Email: M001091@ms.skh.org.tw

Abstract

K. Fujisaki, K. Masutani, T. Yoshimitsu, K. Nakanishi, M. Matsumoto, H. Yagi, H. Ishizashi, Y. Fujimura, K. Takeda, H. Hirakata and M. Iida

¹Division of Nephrology, Aso Iizuka Hospital, Iizuka, ²Department of Medicine and Clinical Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka, ³Division of Pathology, Aso Iizuka Hospital, Iizuka, and ⁴Department of Blood Transfusion Medicine, Nara Medical University, Kashihara, Japan
We present a case of classical polyarteritis nodosa (PN) overlapping thrombotic thrombocytopenic purpura (TTP). A 70-year-old woman was transferred to our hospital because of general fatigue and fever. On admission, laboratory findings revealed leukocytosis, normochromic normocytic anemia and renal dysfunction. About one week later, she developed disturbance of consciousness, and laboratory findings revealed rapidly progressive thrombocytopenia and renal dysfunction. We suspected the presence of microscopic polyangiitis (MPA), based on mild elevation of myeloperoxidase (MPO) anti-neutrophil cytoplasmic antibody (ANCA). On post-admission Day 11, renal biopsy was performed but the diagnosis of MPA could not be confirmed because of the absence of glomerular crescent formation or vasculitis. However, the biopsy specimen showed many collapsed glomeruli and interstitial inflammation, indicating the presence of occlusive lesions, such as vasculitis in larger arteries. We instituted methylprednisolone pulse therapy, cyclophosphamide and plasma exchange, because the clinical symptoms also satisfied the criteria of TTP. Despite the intensive treatment, the patient died on 43rd day of hospitalization due to thalamic hemorrhage. Autopsy showed typical findings of classical PN including disruption of arterial walls and fibrinoid necrosis in the medium-sized arteries of the kidneys and colon. We detected reduced activity of von Willebrand factor-cleaving protease (VWF-CP) and the presence of plasma inhibitory IgG against VWF-CP. A better understanding of the mechanisms would be useful.Correspondence to:
K. Masutani, MD
Department of Medicine and Clinical Science
Graduate School of Medical Sciences
Kyushu University
Maidashi 3-1-1
Higashi-ku, Fukuoka, 812-8582, Japan
Email: masutani@kcu.med.kyushu-u.ac.jp

Abstract

N. Joss, G. Baxter, B. Young, L. Buist and R.S.C. Rodger

¹Renal Transplant, ²Radiology and ³Pathology Departments, Western Infirmary, Glasgow, UK
We report a patient who presented with a solid mass in her graft 15 years after renal transplantation. The appearances by ultrasound were consistent with either malignancy or lobar nephronia (focal acute bacterial nephritis). Biopsy confirmed the diagnosis of a lobar nephronia with marked inflammatory infiltrate and frank pus formation. Treatment with antibiotics was associated with resolution of the mass. Lobar nephronia is a diagnosis based upon renal ultrasonography and must be considered in a patient with a solid mass in the kidney.Correspondence to:
N. Joss, MD Renal Unit, Western Infirmary Dumbarton Road, Glasgow, UK
Email: nicola.joss@northglasgow.scot.nhs.uk

Abstract

H. Izzedine¹, V. Launay-Vacher¹, S. Karie¹, C. Caramella¹, F. de Person² and G. Deray¹

Departments of ¹Nephrology and ²Rheumatology, Pitié-Salpêtrière Hospital, Paris, France
Methotrexate (MTX) has become the most commonly prescribed disease-modifying anti-rheumatic drug. However, toxicity is an important drawback of MTX therapy and permanent discontinuation of MTX for adverse effects occurs in 1 patient out of 10. Although high-dose MTX is known to be nephrotoxic, data on low-dose MTX renal effects are scanty. We report an insidious and progressive deterioration of renal function during long-term low-dose MTX in a 59-year-old woman. Kidney biopsy revealed advanced kidney fibrosis with extensive interstitial and glomerular fibrosis, and vascular sclerosis. We suggest that patients on low-dose MTX therapy even alone, should be periodically monitored for creatinine levels.Correspondence to:
Dr. H. Izzedine
Department of Nephrology
Pitié-Salpêtrière Hospital
83, Blvd de l’Hopital
75013 Paris, France
Email: hassan.izzedine@psl.ap-hop-paris.fr

Abstract

A. Capitanini, A. Lupi, F. Osteri, I. Petrone, C. Del Corso, M. Straniti, M. Gallieni and A. Rossi

¹Civil Hospital, Pescia (Pistoia), and

²San Paolo Hospital, Milano, Italy
Aims: Sevelamer hydrochloride is a polymer containing multiple amines (40% amine hydrochloride) separated by one carbon from the polymer backbone, and it is not absorbed by the intestine. These amines are partially protonated and interact with phosphate molecules through ionic and hydrogen bonding, therefore reducing phosphate absorption and lowering serum phosphate concentration. Alterations of gastric pH, in particular excessive alkalinization, could interfere with sevelamer phosphate binding capacity. Case history: A 30-year-old dialysis patient affected by secondary hyperparathyroidism started sevelamer treatment, 4.8 g/day, with a basal serum phosphate of 6.9 mg/dl. The patient was also treated with omeprazole (20 mg/day) because of chronic gastritis. Phosphate levels normalized (4.2 mg/dl), but after four months of follow-up serum phosphate unexpectedly increased to 7.2 mg/dl. We found out that in the same period she had autonomously increased the dosage of omeprazole to 80 mg/day, due to worsening of dyspepsia. Gastric pH measurement showed a median level of 4.1, rather than the normal values of 1 – 2, indicating excessive pharmacological alkalinization. When omeprazole was reduced to the correct dose of 20 mg/day, we observed a rapid decrease of phosphate levels. Conclusion: This case report highlights the influence of gastric pH on sevelamer phosphate binding capacity. The high dose of omeprazole and the consequent excessive increase in gastric pH was probably responsible for a decreased phosphate binding capacity of sevelamer. When patients taking appropriate doses of sevelamer do not respond to treatment, a potential interaction with drugs determining an increase of gastric pH should be considered. Correspondence to:
A. Capitanini, MD

Division of Nephrology

Civil Hospital of Pescia

51017 Pescia (Pistoia),Italy
Email: drcapitanini@excite.it

Abstract

K. Kano, Y. Yamada, K. Nishikura, E. Kojima and O. Arisaka

Abstract

E. Koca, D. Cetiner, H. Goker, S. Aksu, O.I. Ozcebe, I.C. Haznedaroglu and C. Turgan

Abstract

O. Schück, V. Teplan, O. Marecková, J. Skibová and M. Stollová

Abstract

B. Breuer and C. Hornig

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Volume 64, No. 4/2005(October)