Volume 64, No. 3/2005(September)
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 Clinical Nephrology
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Originals
Clinicopathological features and the prognosis of IgA nephropathy in Japanese children on long-term observation
Abstract
R. Nozawa, J. Suzuki, A. Takahashi, M. Isome, Y. Kawasaki, S. Suzuki and H. Suzuki
Department of Pediatrics, Fukushima Medical University School of Medicine, Fukushima, Japan
Aims: Clinicopathological features were investigated to clarify the ultimate prognosis and prognostic indicators for patients with IgA nephropathy in Japanese children. Methods: We evaluated the outcomes of 181 patients in whom IgA nephropathy was diagnosed before the age of 15 years since September 1979 and followed-up at least for three years with regard to clinical data at the onset of symptoms and renal histologic data. Results: After mean follow-up of 7.3 years from onset, 91 patients of 181 (50.3%) were in clinical remission at the last examination, 24 (13.2%) had isolated hematuria, 59 (32.6%) had hematuria and proteinuria. Eighteen of 59 (9.9%) had proteinuria more than 1 g per 24 hours. Hypertension was observed in 12 cases and 7 (3.9%) developed end-stage renal disease. Except 7, no patient had reduced renal function and elevated serum creatinine at the final follow-up. Predicted renal survival rate from onset was 92.3% at 10 years and 89.1% at 20 years. In multivariable analysis, age at onset and chronic changes of tubulointerstitium were associated with poor outcome. Conclusions: Of 181 children with IgA nephropathy, 50% regressed, remaining 46% had hematuria and/or proteinuria and 4% of patients lapsed into end-stage renal disease. Our results indicate that childhood IgA nephropathy has a benign course and the risk for end-stage renal disease is lower than that of adults. Age at onset and tubulointerstitial lesions were the strong predictors of a progressive course of childhood IgA nephropathy.Correspondence to:
R. Nozawa, MD
Hikarigaoka-1
Fukushima-city, Fukushima, 960-1295, Japan
Email: ruri-n@fmu.ac.jp
Originals
Effects of dual blockade of the renin angiotensin system in hypertensive type 2 diabetic patients with nephropathy
Abstract
J.P.S. Matos, M. de Lourdes Rodrigues, V.L. Ismerim, E.M. Boasquevisque, V. Genelhu and E.A. Francischetti
1Hypertension Clinic, Laboratory of Clinical and Experimental Pathophysiology, 2Department of Clinical Pathology, 3Department of Nuclear Medicine, Rio de Janeiro State University, Rio de Janeiro, Brazil
Aim: To evaluate the effects of combined treatment of an ACE inhibitor and an angiotensin II receptor antagonist on parameters related to the progression of renal disease in type 2 diabetic patients. Methods: 20 hypertensive type 2 diabetic patients with non-nephrotic proteinuria (0.5 – 3.0 g/day) and estimated creatinine clearance ³ 40 ml/min/ 1.73m2 were randomly assigned to be treated with perindopril 8 mg/day (Per), irbesartan 300 mg/day (Irb) or a combination of both with the same doses (Per + Irb). Each treatment phase lasting 16 weeks was preceded by a four-week washout period. Diuretics, clonidine and hydralazine were used as supplementary drugs for blood pressure control. Patients were evaluated at baseline and at the end of each treatment phase. Results: 15 (3M/12F) patients completed all the phases. Use of Per, Irb and Per + Irb led to a reduction in 24-hour mean blood pressure of 6 mmHg, 4 mmHg and 4 mmHg, respectively. Changes in glomerular filtration rate were not significant at any phase. Renal plasma flow was significantly more elevated with Irb than Per. Treatment with both Irb and Per + Irb induced similar plasma renin elevation, but treatment with Per did not, suggesting escape. Plasma aldosterone was reduced only by treatment with Per + Irb (–36%, p < 0.02). Reduction in proteinuria during Per + Irb (–33%) was not significantly different from Per (–34%) or Irb (–22%). Urinary transforming growth factor b1 (TGF-b1) excretion was significantly reduced with both Irb (–24%, p < 0.05) and Per + Irb (–36%, p < 0.05) but not with Per (–11%, p = 0.60). Conclusion: Only combined therapy with irbesartan plus perindopril concurrently reduces plasma aldosterone, proteinuria and urinary TGF-b1.Correspondence to:
E.A. Francischetti, MD
Hospital Universitario Pedro Ernesto
Av. 28 de setembro, 77
20551-030 Rio de Janeiro, Brazil
Email: eafranc@uerj.br
Originals
Fomepizole may change indication for hemodialysis in methanol poisoning: prospective study in seven cases
Abstract
K.E. Hovda, S. Froyshov, H. Gudmundsdottir, N. Rudberg and D. Jacobsen
1Department of Acute Medicine, 2Department of Nephrology, and 3Department of Clinical Chemistry, Ullevaal University Hospital, Oslo, Norway
Background: Treatment of methanol poisoning includes administration of buffer, antidote and hemodialysis. The role of hemodialysis using the new antidote fomepizole has not been studied. We studied the kinetics of methanol and formate during hemodialysis, and the possibility for delayed hemodialysis in the methanol poisoned patients without severe metabolic acidosis or visual disturbances. Patients and methods: Prospective case series study on methanol, formate and dialysis kinetics in 7 cases of severe methanol poisoning treated with buffer, fomepizole and hemodialysis (average 7 hours, range 5 – 8). Four patients were dialyzed early after diagnosis was obtained, while three were dialyzed “electively” the next day. Results: The median pH upon admission was 6.9 (range 6.6 – 7.5) and median base deficit 20.4 mmol/l (range 5.1 – 30.0). Their median S-methanol was 76.3 mmol/l (range 15.6 – 140.6) and S-formate 13.6 mmol/l (range 3.3 – 21). The median half-life of methanol during fomepizole treatment before dialysis was 71.2 hours (range 69.3 – 77); compared to 2.5 hours (range 1.7 – 3.3) during procedure. The median half-life of formate during dialysis was 1.7 hours (range 1.5 – 1.9). The median dialysis clearance of methanol was 222 ml/min (range 204 – 232) and for formate 225 ml/min (range 220 – 229) at a blood flow of 250 ml/min. One patient died and 2 were discharged with permanent visual and cerebral sequelae, whereas one died one year later. All three patients, in whom “elective” hemodialysis was performed, were discharged without sequelae. Conclusion: The efficacy and side effect profile of fomepizole may change the role of hemodialysis in methanol poisoning. More patients may be stabilized in local hospitals and transferred for “elective” dialysis, if methanol removal is still indicated after correction of metabolic acidosis.Correspondence to:
K.E. Hovda, MD
Department of Acute Medicine
Ullevaal University Hospital
0407 Oslo, Norway
Email: knov@uus.no,kehovda@yahoo.no
Originals
Apoptotic markers on lymphocytes and monocytes are unchanged during single hemodialysis sessions using either regenerated cellulose or polysulfone membranes
Abstract
C.-C. Wu, T.-N. Liao, K.-C. Lu, J.-S. Chen, P. Chu, S.-H. Lin, C.-H. Chuang and Y.-F. Lin
1Graduate Institute of Medical Sciences, National Defense Medical Center, and 2Department of Medicine, Division of Nephrology, Tri-Service General Hospital, 3Department of Medical Technology, Chung-Hwa College of Medical Technology, 4Department of Medicine, Division of Nephrology, Cardinal Tien Hospital, Fu-Jen Catholic University, School of Medicine, Taipei, Taiwan
Background: There is an increased rate of apoptosis of peripheral blood mononuclear cells (PBMCs) in patients undergoing hemodialysis (HD), but little is known about how different dialysis membranes may contribute to the process. We, therefore, studied the influence of two different dialysis membranes on apoptotic markers during HD. Methods: 8 healthy controls and 8 patients on regular HD 3 times per week were enrolled in this cross-controlled study. Patients received HD using polysulfone and then regenerated cellulose dialysis membranes for one week each, sequentially. Serum was collected for C-reactive protein (CRP) detection; flow cytometry with dual antibody staining was used to measure the apoptotic markers Fas (CD95), FasL (CD178) and TNF-R2 (CD120b) in T cells (CD3+), B cells (CD19+), and monocytes (CD14+) at 0, 15, 120 and 240 min after starting HD. We also measured total leukocyte numbers and differential white cell counts. Results: Hemodialysis patients revealed lymphocytopenia, monocytopenia, higher CRP levels and higher Fas and TNF-R2 expression on lymphocytes and monocytes at baseline when compared with normal controls. Leukocyte numbers, including neutrophils, lymphocytes and monocytes, dropped significantly after 15 min of dialysis. There were no significant differences in Fas levels during hemodialysis on T and B lymphocytes or on monocytes. T lymphocyte FasL (CD178) levels remained unchanged throughout the process. There was a significantly lower overall level of CD120b at 15 min of HD, whereas this marker was higher on monocytes after dialysis. There were no significant differences in the levels of apoptotic markers between the two membranes. Conclusion: Our results suggest that uremia itself contributes to PBMC apoptosis. The two different dialysis membranes used in this study did not influence apoptotic markers on PBMCs significantly, but increased TNF-R2 expression on monocytes during a single dialysis session.
Correspondence to:
Y. Feng Lin, MD
Division of Nephrology
Department of Medicine
Tri-Service General Hospital, No. 325, Sec. 2
Cheng-Kung Road
Neihu 114, Taipei, Taiwan, ROC
Email: linyf@ndmctsgh.edu.tw
Originals
Comparison of different methods for hemodialysis evaluation by means of ROC curves: from artificial intelligence to current methods
Abstract
E.A. Fernández1, R. Valtuille2, J.M.R. Presedo3 and P. Willshaw4
1Catholic University of Córdoba and Conicet, Córdoba, 2Fresenius Medical Care, Argentina, 3University of Santiago de Compostela, Santiago de Compostela, Spain, and 4School of Health Science, University of Wales, Swansea, UK
Background: The National Kidney Foundation Guidelines (DOQI) and the European Renal Association (ERA) have set standards for adequacy of hemodialysis treatment. They recommended minimum single pool doses of 1.2 (Kt/Vsp DOQI), and 1.4 (Kt/Vsp ERA) and a “standard” urea removal ratio (URR) of 65%. Here, we compare an Artificial Intelligence Method (AIM) based on an Artificial Neural Network (ANN) and the usual methods for hemodialysis treatment follow-up such as Smye, Daugirdas, standard urea reduction ratio (URR using post-dialysis urea concentration) and modified URR [Cheng et al. 2001] against equilibrated Kt/V and URR calculated using a 60 min post-dialysis urea concentration. Methods: We used ROC analysis to evaluate and compare these methodologies. We also propose a method to find a minimum target dose that maximizes the sensitivity, specificity and positive predictive values of the diagnostic tool. Results: From a URR point of view, the ANN, stdURR and mURR perform almost equally well with an area under the curve (AUC) of 0.90, 0.93 and 0.92, respectively, but the ANN achieved the lowest false positive rate (FPR = 7.94%) and error rate (ER = 12.7%). When Kt/V is used as a dose index, the logarithmic single- and double-pool equations perform almost equally (AUC 0.957 and 0.962), and the ANN method achieves an AUC of 0.934. The lowest FPR was for ANN and Kt/Vsp (4.76%), which also achieved the lowest ER of 6.39%. Conclusions: For both cases (URR and Kt/V), the minimum doses required to achieve the lowest FPR and ER for the standard methods (stdURR and Kt/Vsp) were higher than those reported by the DOQI guidelines, being 70% for stdURR and 1.35 for Kt/Vsp, whereas for those methods using the double-pool Kt/V or equilibrated URR, the dose targets were close to those recommended by DOQI and ERA. Our proposed method for target dose selection is easy to understand, and it takes into account both accuracy and confidence of the adequacy tool. We found the ANN method to be superior to the Smye method for estimation of equilibrated urea, and the results presented here suggest that ANN methods could be useful tools in the analysis of nephrology data.Correspondence to:
E.A. Ferández, PhD
Universidad Católica de Córdoba
Fac. de Ingeniería
Camino Alta Gracia Km 10
Córdoba 5000, Argentina
Email: elmerfer@yahoo.com
Originals
Biocompatibility parameters in in-vitro simulated automated versus continuous ambulatory peritoneal dialysis
Abstract
A. Fusshoeller, J. Baehr, B. Tiemann, B. Grabensee and J. Plum
Department of Nephrology, Heinrich Heine University of Düsseldorf, Germany
Background: In peritoneal dialysis, the usage of automated peritoneal dialysis (APD) has been steadily increased. As APD means larger volumes of solution and more frequent contact times with fresh dialysate, an additive negative impact on biocompatibility data, exceeding the known effect of conventional PD fluids, seems possible. For an in-vitro comparison of APD and CAPD, a new cell culture system has recently been established. Methods: A double chamber cell culture system with human mesothelial cells on top of a permeable membrane and growth medium beyond was used for mimicking CAPD and APD. Reflecting the in vivo equilibration pattern, we compared an eight-hour CAPD with a CCPD setting, using a conventional PD solution. Cell viability was assessed with a MTT assay and cell function via constitutive and stimulated IL-6 release. CA125 was measured as a parameter of mesothelial cell integrity, and TGF-1b was measured as an index of induction of fibrosis. Results: Both the CAPD and the CCPD mode resulted in a significantly lower MTT assay and stimulated IL-6 release compared to growth medium. TGF-1b and CA125 release did not differ between the PD modes and control. The CAPD and the CCPD mode itself did not differ with regard to MTT assay, IL-6 release, TGF-1b and CA125 generation. Conclusion: From the in-vitro model imitating the acute exposure of mesothelial cells with conventional PD fluid in a CCPD and CAPD mode, there is no evidence that APD, due to the larger volumes of solution and more frequent contact times with fresh dialysate, has an acute, additive negative impact on biocompatibility parameters indicative for peritoneal host defense, mesothelial cell integrity and peritoneal fibrosis.Correspondence to:
Dr. A. Fußhöller
Moorenstraße 5
40225 Düsseldorf, Germany
Email: Andreas.Fusshoeller@uni-duesseldorf.de
Case reports
A case of monoclonal immunoglobulin light- and heavy-chain deposition disease exhibiting atypical deposition with fibrillary structures, successfully treated with chemotherapy
Abstract
A. Nakatsuka, Y. Maeshima, A. Sarai, H. Yanai, H. Sugiyama, Y. Yamasaki and H. Makino
1Department of Medicine and Clinical Science, 2Department of Pathology, Okayama University Graduate School of Medicine and Dentistry, Okayama, Japan
We report a case of light and heavy chain deposition disease (LHCDD), a rather rare monoclonal immunoglobulin deposition disease (MIDD) with successful therapeutic effect. A 58-year-old woman suffered from proteinuria and renal insufficiency (serum creatinine 1.0 mg/dl, creatinine clearance 49.2 ml/min) in February 2003. In serum and urine samples, monoclonal IgG-k was detected. A bone marrow aspiration showed a slightly hypocellular marrow and plasma cell population was increased to 7.0%. Renal histological findings revealed lobulated glomeruli with nodular lesions on light microscopy, characteristic findings of MIDD. Intense deposition of IgG heavy chains in the linear pattern in the glomerular and tubular basement membranes was observed. Immunohistochemistry revealed both k and l light chain depositions in glomeruli. Electron-microscopic examination revealed fine granular electron-dense deposits accompanied by microfibrils. Based on these findings, this patient was diagnosed as LHCDD. She received three courses of melphalan and prednisone chemotherapy, resulting in disappearance of proteinuria, prevention of renal functional deterioration and the decrease of monoclonal immunoglobulin. This case clearly demonstrates that the earlier and accurate diagnosis and initiation of chemotherapy at the early stage with serum creatinine level below 4.0 mg/dl are necessary to improve renal and patient outcome.Correspondence to:
Dr. Y. Maeshima
Assistant Professor of Medicine
Department of Medicine and Clinical Science
Okayama University
Graduate School of Medicine and Dentistry
2-5-1 Shikata-cho
Okayama, 700-8558, Japan
Email: ymaeshim@md.okayama-u.ac.jp
Case reports
Nephrotic syndrome preceding Hodgkin's lymphoma by 13 months
Abstract
N. Bhatt
University Hospital of Wales, Cardiff, UK
This report documents the occurrence of a minimal change nephrotic syndrome in a patient antedating the recognition of Hodgkin’s lymphoma. An 18-year-old woman presented with the clinical symptoms of nephrotic syndrome and was started on prednisolone with partial response. 13 months after the diagnosis was made, she presented with weight loss and right upper abdominal pain for two months. Kidney biopsy revealed minimal change glomerulonephritis. She subsequently developed cervical lymphadenopathy, which on excision biopsy report, turned out to be Hodgkin’s disease, nodular sclerosing type. Hodgkin’s lymphoma clinical stage IIIB was diagnosed. A review of literature yielded altogether three cases in which the onset of nephrotic syndrome preceded the diagnosis of Hodgkin’s lymphoma by more than 12 months.Correspondence to:
N. Bhatt, MD
Carmathen flat, Carmarthen House
University Hospital of Wales
Heath Park Cardiff CF14 4XW, UK
Email: bhattradio@hotmail.com
Case reports
De novo seropositive rheumatoid arthritis during immunosuppressive treatment after kidney transplantation
Abstract
T. Forslund, J. Ahonen, E. Elomaa, T. Parviainen and I. Matinlauri
1Renal Unit, 2Division of Rheumatology, Department of Medicine, 3Department of Radiology, 4Department of Clinical Physiology, Central Finland Health Care District Hospital of Jyväskylä, and 5Department of Tissue Typing, Finnish Red Cross, Blood Service, Helsinki, Finland
We detected de novo seropositive erosive rheumatoid arthritis (RA) in a patient seven years after successful cadaveric kidney transplantation (RTx). RA developed in spite of treatment with cyclosporine A (CyA), methylprednisolon (MP) and azathioprine (Aza), compounds often also used for treatment of active RA. Renal failure was due to diabetes mellitus (DM) nephropathy. Besides a slight increase in C-reactive protein (CRP) concentration two years after RTx, the clinical symptoms of RA were observed seven years after RTx. RA was confirmed by X-ray examination, isotopic skeletal scan and positive serum RA factor. After switching Aza to methotrexate (Mtx) treatment, his symptoms disappeared and CRP concentration returned to normal. Our patient had HLA DRB1*0101, *0401 alleles and DQB1*0501, *0302 alleles which have strong genetic association with both DM and RA. To our best knowledge, this is the first case in which de novo seropositive erosive RA developed while on treatment with triple immunosuppression after RTx. The immunosuppressive treatment probably masked the inflammation and symptoms of RA.Correspondence to:
T. Forslund, MD, PhD
Head of Renal Unit
Department of Internal Medicine
Central Finland Health Care District Hospital of Jyväskylä
40100 Jyväskylä, Finland
Email: terje.forslund@ksshp.fi,terje.forslund@med.uib.no
Case reports
Supplement nephropathy due to long-term, high-dose ingestion of ascorbic acid, calcium lactate, vitamin D and laxatives
Abstract
T. Ohtake, S. Kobayashi, K. Negishi and H. Moriya
Department of Nephrology, and Kidney and Dialysis Center, Shonan Kamakura General Hospital, Yamazaki, Kamakura, Japan
A 48-year-old Japanese woman previously in good health was found to have severe proximal tubular dysfunction with a high serum level of ascorbic acid (57.3 mg/ml, reference range: 1.9 – 15.0 mg/ml). Renal biopsy specimen showed marked tubulointerstitial damage, i.e. tubular atrophy, dilatation of tubular lumen with flattened tubular epithelial cells, vacuolization of proximal and distal tubular epithelial cells, and severe interstitial fibrosis with mild infiltration of mononuclear cells. Calcified lesions, which caused tubular obstruction or stenosis, were also seen in interstitial area adjacent to degenerated proximal tubuli. Hypokalemic nephropathy, probably due to long-term use of laxatives, was clearly shown. However, calcified lesions seemed to be caused by inappropriate excessive daily ingestion of ascorbic acid (6 000 mg/day), calcium lactate, and vitamin D because of the patient’s misunderstanding that these supplements could keep her in a good health. This condition may be clinically called “supplement nephropathy”.Correspondence to:
T. Ohtake, MD, PhD
Department of Nephrology and Kidney and Dialysis Center
Shonan Kamakura General Hospital
1202-1 Yamazaki
Kamakura, 247-8533, Japan
Email: ohtake@shonankamakura.or.jp
Letters to the Editor
Amyloidosis: an infrequent cause of non-diabetic renal disease in patients with type 2 diabetes mellitus
Abstract
D. Torun, F. Bolat, S. Sezer and F.N. Ozdemir
Letters to the Editor
Duodenal biopsy may be preferred first for diagnosis of renal amyloidosis in patients with nephrotic syndrome
Abstract
A. Zumrutdal, R. Ozelsancak, F. Bolat, S. Sezer and F. Nurhan Ozdemir
Letters to the Editor
Post-splenectomy pseudohyperkalemia in a patient with chronic idiopathic myelofibrosis and thrombocytosis
Abstract
F. Nakhoul, R. Ramadan, M. Maron and Z. Abassi
Letters to the Editor
Intravenous immunoglobulin- induced reversible neutropenia in a renal transplant patient
Abstract
A. Singh, F. Arif and S.D. Smith
