Volume 57, No. 4/2002(April)
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 Clinical Nephrology
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Original
Analysis of three genetic markers in IgA nephropathy patients from a single region
Abstract
M. Drouet1, C. Aupetit1, Y. Denizot1, M. Bois3, F. Bridoux4, J.C. Aldigier2 and M. Cogné1
1Service d’Immunologie CNRS UMR 6101, Faculté de Médecine, 2Service de Néphrologie, CHRU Dupuytren, Limoges, 3Laboratoire d’Histocompatibilité, Centre de Transfusion Sanguine, Poitiers, and 4Service de Nephrologie, CHRU de la Milèterie, Poitiers, France
Background: IgA nephropathy (IgA-N) is the most common glomerular disease. Various genetic factors have been suspected to influence the disease, but they never have been studied in the same cohort of patients. Methods: In 125 IgA-N biopsy-proven cases, we studied by DNA techniques the allele distribution of 3 polymorphic loci: the angiotensin-converting enzyme (ACE) gene, the specific HLA-DQB1 gene and the hs1,2 enhancer of the alpa1 gene of the IgH locus. Patients were classified as progressive and non-progressive based on a creatininemia above 150 µl/ml or/and a deterioration of the clearance greater than 3 ml/min/year. We analyzed the influence of the polymorphism on the development and the progression of the disease. The control group consisted of 83 heathly subjects. Results: The frequency of HLA-DQB1*0602 was decreased in IgA-N patients (3.6% vs 10.2%, Pc = 0.04, RR = 0.36), suggesting a protective effect of this allele for IgA-N. Kaplan-Meyer analysis with the Cox-proportional hazard model revealed a shorter time between diagnosis and renal failure in patients with the B allele for the a1 gene hs1,2 enhancer (p = 0.04). ACE polymorphism did not influence the development or the progression of the disease. Conclusion: Genes controlling the immune response, such as HLA DQB1 and the a1 transcriptional enhancer gene, may influence the development and/or the progression of IgA-N nephropathy. Patients who develop an IgA-N nephropathy have a higher risk of severe evolution if they have a profile of high IgA humoral responder.Correspondence to:
Dr. M. Drouet; Service d’Immunologie et Immunogénétique, 2 Avenue Martin Luther King, CHRU Dupuytren, F-87000 Limoges, France
Email: drouet@unilim.fr
Original
Plasma bone-specific alkaline phosphatase changes in hemodialysis patients treated by alfacalcidol
Abstract
P. Ureña1,3, O. Bernard-Poenaru2,3, M. Cohen-Solal3 and M.C. de Vernejoul3
1Service de Néphrologie-Dialyse, Clinique de l´Orangerie, Aubervilliers, 2Service Central de Biophysique, Laboratoire de Biologie Endocrinienne, Hôpital Lariboisière, Paris, Cedex, and 3Inserm Unité 349, Hôpital Lariboisière, Paris, France
Vitamin D derivatives correct high bone remodeling by decreasing plasma iPTH concentration in uremic patients with secondary hyperparathyroidism. However, without bone biopsy, plasma iPTH alone might not provide sufficient information regarding vitamin D-induced bone changes. Plasma bone-specific alkaline phosphatase (bAP) seems more sensitive than iPTH in assessing the degree of bone remodeling. We prospectively studied the evolution of iPTH and bAP in 14 adult hemodialysis patients treated for 1 year by i.v. alfacalcidol pulses. The mean total alfacalcidol dose was 0.08 ± 0.02 g/kg/week. Ten patients completed the study, 2 patients had to be parathyroidectomized before week 24 because of hypercalcemia and uncontrolled hyperphosphatemia, and 2 other patients died before week 36. Mean iPTH levels diminished from 826 ± 300 pg/ml (range 507 – 1500 pg/ml) at baseline to 436 ± 371 pg/ml (range 18 – 1,095 pg/ml) after 52 weeks of treatment (48% of decrease). Only 2 patients normalized plasma iPTH levels while 8/10 normalized bAP. Five patients remained with plasma iPTH concentrations higher than 5-fold the normal value. In contrast, plasma bAP levels declined from 47.6 ± 32.2 ng/ml (range 15.4 – 130.0 ng/ml) at baseline to 17.8 ± 9.9 ng/ml (range 8.0 ± 38.0 ng/ml) at week 52 (63% of decrease). Bone histomorphometry was available in 6 patients after 15.8 ± 5.1 months of alfacalcidol treatment. None of them met the criteria of adynamic bone disease as they had increased bone resorption and marrow bone fibrosis. Bone formation rate was normal in 2 patients and unmeasurable in the other 4. Two patients showed signs of osteomalacia. In conclusion, alfacalcidol preferentially reduced bone formation rate rather than the other histological parameters of secondary hyperparathyroidism. It reduced plasma bAP more efficiently than iPTH.Correspondence to:
Dr. M.C. de Vernejoul; Inserm Unité 349, Centre Viggo Petersen, Hôpital Lariboisière, 2, rue Ambroise Paré, F-75475 Paris, Cédex 10, France
Email: brigitte.gouin@inserm.lrb.ap-hop-paris.fr
Original
Effect of biocompatibility of hemodialysis membranes on mortality in acute renal failure: a meta-analysis
Abstract
B.L. Jaber1, J. Lau2, C.H. Schmid2, S.A. Karsou1, A.S. Levey1 and B.J.G. Pereira1
1Divisions of Nephrology and 2Clinical Care Research, Department of Medicine, New England Medical Center Hospitals, Boston, MA, USA
Background: The effect of biocompatibility of hemodialysis membranes on mortality in acute renal failure (ARF) has been a subject of intense debate, with some, but not all studies reporting a lower risk of death among patients with ARF dialyzed with biocompatible membranes (BCM) compared to bioincompatible membranes (BICM). Objectives: We performed a meta-analysis of group data extracted from previously published studies of controlled clinical trials to assess the impact of BCM on the mortality among patients with ARF who required intermittent hemodialysis (IHD). Methods: BCM and BICM were defined as synthetic and cellulose-derived membranes (cuprophan and cellulose acetate), respectively. All controlled clinical trials comparing the effect of BCM to BICM on clinical outcomes in the setting of ARF were included. Original articles as well as abstracts were included. Data in Tables, Figures, and text were independently extracted by 2 of the authors. Risk ratios (RR) for mortality were combined using the random-effects model. Results: Seven studies with a total of 722 patients met the inclusion criteria. One hundred seventy-two (45%) of 384 patients died in the BCM group, compared with 156 (46%) of 338 patients in the BICM group. The RRs for mortality ranged from 0.56 – 1.28. Overall, the pooled RR for mortality was 0.92 (95% CI = 0.76 – 1.13) in favor of the BCM group. However, the test for heterogeneity in RR among studies was significant (chi2 = 8.6, p < 0.05). One study accounted for this significance, and once removed from the model, the RR for mortality was 0.94 (95% CI = 0.79 – 1.12), and the test for heterogeneity among studies lost its significance. Subgroup analyses comparing BCM to cuprophan membranes revealed that the RR for mortality was 0.82 (95% CI = 0.62 – 1.08) in favor of the BCM group, whereas in the subgroup of studies comparing BCM to cellulose acetate, the RR for mortality was 1.11 (95% CI = 0.87 – 1.44) in favor of the BCM group. Conclusion: This meta-analysis demonstrates that the use of BCM does not significantly affect mortality among patients with ARF who require IHD. However, subgroup analyses suggest that cellulose acetate membranes may offer a survival advantage when compared with synthetic membranes, which, in turn, may be more beneficial than cuprophan membranes. Available evidence does not permit a recommendation for or against the use of BCM in ARF. Large trials and pooled analyses of individual patient-level data will be required to assess sources of variability among studies and non-fatal outcomes of ARF.Correspondence to:
Dr. B.L. Jaber; Division of Nephrology, Box 391, New England Medical Center Hospitals, 750 Washington Street, Boston, MA 02111, USA
Email: bjaber@lifespan.org
Original
Comparison between oscillometric and auscultatory methods of ambulatory blood pressure measurement in hemodialysis patients
Abstract
R.M. Fagugli, L. Vecchi, F. Valente, P. Santirosi and M.M. Laviola
Nephrology and Dialysis Unit, Silvestrini Hospital, Perugia, Italy
Introduction: 24-hour ambulatory blood pressure monitoring (ABPM) is commonly used in clinical and research practice. Different methods have been used in BP recording, cuff-oscillometric or Korotkoff sound, and validation studies during ABPM have been performed on general as well as hypertensive populations. Hemodialysis (HD) patients have a high percentage of complications, such as vascular diseases, and they are subject to hyperkinetic blood flows and abrupt body weight changes secondary to HD, which can invalidate BP recording. Therefore, we wanted to compare the 2 methods on an HD population. Patients and methods: We performed 86 ABPMs on 44 patients (aged 60.8 ± 17.2 years) by using a device capable of the simultaneous recording of oscillometric and auscultatory BP (A&D Takeda TM2421). The data obtained with the 2 different ABPM methods have been compared, and the differences between auscultatory and oscillometric determinations have been analyzed, as presented by Bland and Altman [1986]. Results: The percentage of valid recordings was significantly higher with the oscillometric method than with the auscultatory method (93.6 ± 11.3% vs. 71.7 ± 17.04%, p < 0.001). 24-hour diastolic BP and night-time systolic BP were higher when recorded with the oscillometric method (DBP = 75.4 ± 9.6 mmHg vs. 71.8 ± 9.6 mmHg, p < 0.001, asleep SBP = 119.7 ± 23.3 mmHg vs. 116.2 ± 25.0 mmHg, p < 0.001), and the systolic night/day BP ratio was also higher (0.92 ± 0.10 vs. 0.90 ± 0.10, p < 0.001). Finally, the BP coefficient of variation ((SD/mean BP) × 100) was higher when auscultatory determinations were used (16.1 ± 4.6 vs. 14.6 ± 4.9). The limits of agreement between auscultatory and oscillometric BP determinations were for SBP = –6.44; 7.84 and for DBP = –3.66; 10.86. Conclusions: Differences between 24-hour oscillometric and auscultatory ABPM were reported in HD patients: the diastolic 24-hour and asleep systolic BP values and the systolic night/day ratio obtained with the oscillometric method were significantly higher. The higher coefficient of variation reported with the auscultatory method and the wider limits of agreement suggest that the 2 methods do not fully coincide and, in our opinion, the oscillometric method is preferable, due to the higher number of 24-hour valid measurements.Correspondence to:
Dr. R.M. Fagugli; U.O. Nefrologia e Dialisi, Ospedale Silvestrini, Azienda Ospedaliera di Perugia, S. Andrea delle Fratte, I-06100 Perugia, Italy
Email: rmfag@tin.it
Original
Leukopenia and thrombocytopenia in hemodialysis patients with hepatitis B or C virus infection and non-hemodialysis patients with hepatitis cirrhosis
Abstract
Y.-Y. Ng1, C.-C. Lin1, S.-C. Wu2, S.-J. Hwang1, C.-H. Ho1, W.-C. Yang1 and S.-D. Lee1
1Department of Medicine, Taipei Veterans General Hospital, and 2Institute of Public Health, National Yang-Ming University School of Medicine, Taipei, Taiwan, Republic of China
Aims: To investigate the relation of leukopenia and thrombocytopenia in hemodialysis (HD) patients with hepatitis C virus (HCV) infection. Materials and methods: The study included 86 HD patients with hepatitis B surface antigen-negative and hepatitis C antibody-negative, 28 HD patients with hepatitis C antibody-positive, 22 HD patients with hepatitis B surface antigen-positive, 78 non-HD patients with hepatitis B-induced liver cirrhosis and 38 non-hemodialysis patients with hepatitis C-induced liver cirrhosis. The following parameters were checked: anti-HCV, hepatitis B surface antigen, hemoglobin, hematocrit, white blood cells, platelets, calcium, phosphate, iron, ferritin, albumin, globulin, aspartate transaminase (AST), alanine transaminase (ALT) and C-reactive protein. The history of blood transfusions, medications, erythropoietin doses and adequate dialysis (KT/V) for 6 consecutive months was also recorded from charts. Results: The HD patients with positive serum anti-HCV and non-HD patients with hepatitis B- or C-induced liver cirrhosis had higher prevalences of leukopenia (39.3%, 43.6% and 50% vs. 15.1%; p < 0.001) and thrombocytopenia (67.9%, 89.7% and 81.6% vs. 34.9%; p < 0.001) than HD patients with serum anti-HCV(–)HbsAg(–). The WBC (4,432 ± 1,394, 4,792 ± 2,263 and 4,624 ± 2,446 vs. 5,590 ± 1,500/mm3; p < 0.001) and platelet counts (140 ± 45, 80 ± 50 and 89 ± 65 vs. 186 ± 62 × 103/mm3; p < 0.001) of HD patients with positive serum anti-HCV and non-HD patients with hepatitis B- or C-induced cirrhosis were also lower than HD patients without anti-HCV antibody. The liver cirrhosis patients had more thrombocytopenia than the HD patients with anti-HCV(+). The WBC and platelet counts did not vary between HD patients with HbsAg(+) and HD patients with anti-HCV(–)HBsAg(–). The durations of HD, hepatitis and liver cirrhosis were not related to the leukopenia or thrombocytopenia (p > 0.05). Conclusions: HCV infection associated with leukopenia and/or thrombocytopenia in HD patients is as common as in non-HD patients with liver cirrhosis. This may be due to the direct effect of hemopoiesis rather than the hyperspleenism of liver cirrhosis patients. There is a need for further prospective investigation to ascertain the clinical significance of leukopenia and thrombocytopenia in HD patients with anti-HCV(+). The prevalence of leukopenia and thrombocytopenia was higher in HD patients with hepatitis C than in HD patients with hepatitis B and HD patient without hepatitis.Correspondence to:
Dr. Y.-Y. Ng; Department of Medicine, Taipei Veterans General Hospital, 201, Shih-Pai Road, Sec. 2, Taipei, Taiwan 112, Republic of China
Email: ngyy@vghtpe.got.tw
Original
Effects of candesartan and perindopril on renal function, TGF-b1 plasma levels and excretion of prostaglandins in stable renal allograft recipients
Abstract
G.R. Hetzel1, D. Hermsen2, T. Hohlfeld3, A. Rettich1, F. Özcan1, A. Fußhöller1, B. Grabensee1 and J. Plum1
1Klinik für Nephrologie und Rheumatologie, 2Institut für klinische Chemie und Laboratoriumsdiagnostik, and 3Institut für Pharmakologie und klinische Pharmakologie, Heinrich-Heine-Universität, Düsseldorf, Germany
Aims: Although on account of their nephroprotective effects, ACE inhibitors and angiotensin receptor antagonists appear to be advantageous for patients after renal transplantation, their use in these patients has been limited up to now. This is in part due to the risk of inducing a decrease in the glomerular filtration pressure gradient with subsequent impairment of allograft function. The aim of the present study was to investigate the effects of ACE inhibitors and angiotensin receptor antagonists on renal function, excretion of prostaglandins as a parameter of glomerular hemodynamics and TGF-b1 plasma levels during an 8-week withdrawal phase in pretreated patients. Patients and methods: Sixteen patients with stable long-term allograft function undergoing therapy with candesartan (group 1) and 16 patients with stable long-term allograft function undergoing therapy with perindopril (group 2) were included in the study. Any signs of chronic allograft dysfunction were defined as exclusion criteria. Renal function, albuminuria, TGF-b1 plasma levels as well as the excretion of thromboxane B2 and 6-keto-prostaglandin-F-1a were monitored during an 8-week withdrawal phase of the angiotensin receptor antagonist or ACE inhibitor, respectively. Normotension was maintained throughout the study period through adjustment of other antihypertensive drugs. Results: Creatinine clearance as well as TGF-b1 plasma levels and the excretion of prostaglandins remained unchanged after discontinuation of candesartan or perindopril. However, after withdrawal of the substances a significant increase in albuminuria was noted in both patient groups throughout the observation period. After 8 weeks, median albuminuria had increased by 63% in group 1 and by 163% in group 2. Conclusions: We were able to demonstrate that the use of ACE inhibitors and angiotensin receptor antagonists in patients after renal transplantation is safe. Favorable effects of both substances on albuminuria were detectable in patients who showed no signs of chronic allograft dysfunction according to the usual criteria. Therefore, a nephroprotective effect of candesartan as well as of perindopril, is highly probable in patients after renal transplantation. Further investigations regarding routine use in these patients are therefore mandatory.Correspondence to:
Dr. G.R. Hetzel; Klinik für Nephrologie und Rheumatologie, Medizinische Einrichtungen der Heinrich-Heine-Universität, Moorenstraße 5, D-40225 Düsseldorf, Germany
Email: hetzel@med.uni-duesseldorf.de
Case Report
Membranoproliferative glomerulonephritis associated with low-grade B cell lymphoma presenting in the kidney
Abstract
M.B. Stokes1, B. Wood2 and Ch.E. Alpers2
1Department of Pathology, New York University Medical Center, New York, NY, 2Departments of Pathology and Laboratory Medicine, University of Washington Medical Center, Seattle, WA, USA
Low-grade B cell lymphoma of mucosa-associated tissue type (MALToma) rarely may involve the kidney. Membranoproliferative glomerulonephritis (MPGN) is an uncommon complication of B cell lymphoma and may be related to cryoglobulin and/or immunoglobulin synthesis by a secretory B cell clone. We report 2 patients with the novel renal biopsy findings of coexistent MALToma and MPGN. Both subjects presented with nephrotic proteinuria and renal insufficiency. One patient had a serum M protein (IgG k) but neither individual had any other clinical or serologic evidence of systemic disease, including hematolymphoid malignancy, autoimmune disease, cryoglobulinemia, or hepatitis C viral infection. Both renal biopsies demonstrated MPGN type I with immunoglobulin deposits that in 1 case showed light chain restriction (IgM k). Electron microscopy disclosed corresponding glomerular electron dense deposits in subendothelial locations. Both biopsies also contained atypical interstitial lymphoid infiltrates comprising marginal zone (centrocyte-like) cells that infiltrated tubules and showed extra-capsular extension. Immunostains demonstrated a predominantly B cell population that lacked expression of CD5 and cycline D1, and gene rearrangement studies confirmed the presence of a monoclonal B cell population in both cases. These findings indicate that low-grade B cell lymphoma in the kidney may be an unexpected finding in patients with nephrotic syndrome related to MPGN. Immunophenotypic and gene rearrangement studies are important ancillary tools for the evaluation of atypical lymphoid infiltrates in kidney biopsies.Correspondence to:
M.B. Stokes, MB; Department of Pathology, TH 480, NYU Medical Center, 560 First Avenue, New York, NY 10016, USA
Email: barry.stokes@ med.nyu.edu
Case Report
Carbamazepine-induced acute granulomatous interstitial nephritis
Abstract
J. Hegarty1, M. Picton1, G. Agarwal2, A. Pramanik2 and P.A. Kalra1
1Department of Renal Medicine, and 2Department of Elderly Care Medicine, Hope Hospital, Salford, UK
A 79-year-old man, newly started on carbamazepine, presented with rash, eosinophilia and liver dysfunction progressing to acute renal failure despite discontinuation of the anti-epileptic agent. Percutaneous renal biopsy revealed acute granulomatous interstitial nephritis, which responded successfully to high-dose oral steroid therapy.Correspondence to:
Dr. J. Hegarty; Department of Renal Medicine, Hope Hospital, Stott Lane, Salford M6 8HD, UK
Email: jan.hegarty@ ticketbox.net
Case Report
Retroperitoneal fibrosis: a case report of spontaneous resolution
Abstract
S. Pierre1, P.E. Cordy2 and H. Razvi1
1Division of Urology and, 2Department of Medicine (Nephrology), St. Joseph’s Health Care and the University of Western Ontario, London, Ontario, Canada
Aim: The purpose of this case report is to document an occurrence of spontaneous resolution of idiopathic retroperitoneal fibrosis and to review the investigation and management of this unusual condition. Materials and methods: A detailed case summary of a patient with retroperitoneal fibrosis is presented. Current citations in Index medicus from the English-speaking literature of relevance to the topic were reviewed. Conclusions: In this patient who refused open surgical intervention, bilateral stent placement allowed stabilization of renal function. CT-guided biopsy did not reveal malignancy. Serial CT imaging demonstrated gradual disappearance of the retroperitoneal mass. From the literature review, spontaneous resolution of this condition appears to be a rare phenomenon. Although often utilized, CT-guided biopsy may fail to exclude the presence of malignancy. Open surgical biopsy of the retroperitoneal mass and ureterolysis remain the standard of care for operative candidates. Establishing renal drainage and considering a trial of steroids or surveillance may be an option in carefully selected individuals.Correspondence to:
Dr. H. Razvi, Division of Urology, St. Joseph’s Health Care, 268 Grosvenor St., London, Ontario, Canada N6A 4V2
Email: hrazvi@julian.uwo.ca
Case Report
Unilateral renal cystic disease – report of one case and review of literature
Abstract
S.-P. Lin, J.-M. Chang, H.-C. Chen and Y.-H. Lai
Division of Nephrology, Department of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan
Clinical presentation of unilateral renal cystic disease (URCD) is characterized by multiple simple cysts in only 1 kidney. Involvement of other intra-abdominal organs is not found. Renal function is usually preserved despite the existence of multiple cysts. No genetic background can be delineated up to the present. We present 1 patient with URCD, who was evaluated for his right flank pain. Urinalysis and biochemical tests showed normal renal function (BUN 5.03 mmol/l, creatinine 110.5 mmol/l). Ultrasonographic examination was done and it revealed 2 right renal stones. Furthermore, multiple renal cysts over the juxta-medullary area were noted. His left kidney was intact. Computed tomography (CT) of both kidneys confirmed this finding. 99mTc-DTPA renal scan showed that the glomerular filtration rate of both kidneys was not significantly different. There was no family history of renal diseases. His parents, grandparents and siblings were examined for possible kidney lesions, but none of them had any renal cystic lesion. This patient was followed for only a relatively short period of time (3 years) and his renal function did not deteriorate. Follow-up image studies with sonography and CT were not different from the previous ones.Correspondence to:
Dr. Y.-H. Lai; Division of Nephrology, Department of Medicine, Kaohsiung Medical University, 100 Shih-Chuan 1st Road, Kaohsiung 807, Taiwan
Email: yuhsla@kmu.edu.tw
Letter to the editor
Relationship between urea reduction ratio (URR) and Kt/V in hemodialysis
Abstract
G. Virga, C. Gardin, S. Mastrosimone and A. Bonadonna
