Volume 73 (2010), No. 6/2010(June)
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Lead article
Acute tubulointerstitial nephritis related to antituberculous drug therapy
C. Schubert, W.D. Bates and M.R. Moosa
Page No. 413
Abstract
Clinical Nephrology, Vol. 73 – No. 6/2010 (413-419)
Acute tubulointerstitial nephritis related to antituberculous drug therapy
C. Schubert1, W.D. Bates2 and M.R. Moosa3
1Nephrologist, 2Division of Anatomical Pathology, Department of Pathology, NHLS (National health laboratory service) and 3Division of Nephrology, Department of Medicine, University of Stellenbosch, Cape Town, South Africa
Background: Acute tubulointerstitial nephritis (ATIN) as a complication of antituberculous therapy has been most commonly reported due to rifampicin therapy. This reaction typically occurs following re-exposure to the drug. This study undertook to investigate the clinicopathological features of ATIN related to antituberculous therapy. Methods: We performed a retrospective study of all adult patients with a biopsy-proven diagnosis of ATIN on chemotherapy for tuberculosis. The patients presented with acute renal failure at our institution during 1995 – 2007. The demographic, clinical, biochemical and histopathological features were studied. The patient outcome and management were analyzed. Results: 41 patients had histologically proven ATIN. 23 (56%) were female. The mean age at presentation was 42 years. The most common regimen included rifampicin used intermittently to treat pulmonary tuberculosis. The average duration of antituberculosis therapy was 19 days before presentation and the duration of the acute illness averaged 5 days. The most common clinical manifestation included gastro-intestinal symptoms occurring in 35 (85%) patients with associated hepatitis biochemically in 20 (53%) patients. No skin rashes were observed and eosinophilia was only present in two patients. Hematuria was observed universally without any significant proteinuria. Anemia was present in 37 (90%) patients, with associated thrombocytopenia in 15 (37%). Rifampicin was discontinued in 37 (90%) cases. Nine (22%) patients required dialysis. One patient failed to recover renal function and 4 (10%) patients died. Mortality was related to overwhelming tuberculosis infection. The main factor predicting the need for dialysis was duration of oliguria. Conclusion: ATIN is a rare, but serious complication of repeat antituberculous therapy mainly due to re-exposure to rifampicin. Although the renal prognosis is generally good the disease does carry significant morbidity and mortality risks. A high index of suspicion is needed in re-treatment patients. A suggested screening test is for microhematuria with urine dipstix.Correspondence to:
Prof. M.R. Moosa
Department of Medicine
Tygerberg Hospital
P.O. Box 19063
Parow, 7505, South Africa
Email: [email protected]
Original
Homocysteine and folic acid levels in hemodialysis patients treated with sevelamer hydrochloride
S. Goto, H. Fujii, J.-I. Kim and M. Fukagawa
Page No. 420
Abstract
Clinical Nephrology, Vol. 73 – No. 6/2010 (420-425)
Homocysteine and folic acid levels in hemodialysis patients treated with sevelamer hydrochloride
S. Goto1, H. Fujii1, J.-I. Kim2 and M. Fukagawa1,3
1Division of Nephrology and Kidney Center, Kobe University, School of Medicine, Kobe, 2Department of Internal Medicine, Chibune General Hospital, Osaka, and 3Division of Nephrology and Metabolism, Tokai University School of Medicine, Isehara, Japan
Background/aims: Folic acid deficiency has been reported to elevate plasma homocysteine levels and result in hyperhomocystinemia, which is an independent risk factor for cardiovascular disease. Sevelamer hydrochloride has the potential to bind with folic acid. To determine this effect of sevelamer hydrochloride on plasma homocysteine levels, change in serum folic acid and plasma homocysteine levels after administration of sevelamer hydrochloride in chronic hemodialysis patients was evaluated. Methods: Sevelamer hydrochloride was administered to 26 outpatients undergoing hemodialysis for 3 months. Serum and plasma samples were collected just before the dialysis session at baseline and 3 months. Results: Three months after the administration of sevelamer hydrochloride, serum folic acid levels significantly decreased (baseline vs. 3 months; 5.48 ± 1.81 vs. 4.79 ± 1.79 ng/ml, p < 0.05), whereas plasma homocysteine levels significantly increased (baseline vs. 3 months; 50.8 ± 35.9 vs. 67.6 ± 44.7 nmol/ml, p < 0.01). Conclusion: These findings suggest that sevelamer hydrochloride elevates plasma homocysteine levels, possibly by inhibiting the absorption of folic acid. Thus, the effect of sevelamer hydrochloride should be excluded while evaluating the increased plasma levels of homocysteine.Correspondence to:
M. Fukagawa, MD, PhD, FASN
Professor of Medicine
Division of Nephrology and Metabolism
Tokai University School of Medicine
143 Shimo-Kasuya, Ishehara
Kanagawa, 259-1193, Japan
Email: [email protected]
Original
The German registry for nephrogenic systemic fibrosis: findings from 23 patients
S. Becker, S. Walter, O. Witzke, B. Wilde, U. Hillen, D. Napieralski, A. Kreuter, P. Altmeyer, G. Schieren, A. Daul, L.-C. Rump and A. Kribben
Page No. 426
Abstract
Clinical Nephrology, Vol. 73 – No. 6/2010 (426-430)
The German registry for nephrogenic systemic fibrosis: findings from 23 patients
S. Becker1, S. Walter1, O. Witzke1, B. Wilde1, U. Hillen2, D. Napieralski3, A. Kreuter4, P. Altmeyer4, G. Schieren5, A. Daul6, L.-C. Rump5 and A. Kribben1
1Department of Nephrology, University Duisburg-Essen, 2Department of Dermatology, University Duisburg-Essen, 3Department of Controlling, University Duisburg-Essen, Essen, 4Department of Dermatology, Ruhr-University Bochum, Bochum, 5Department of Nephrology, Heinrich-Heine-University Düsseldorf, Düsseldorf, and 6Department of Nephrology, Elisabeth Krankenhaus Essen GmbH, Essen, Germany
Background and aim: Nephrogenic systemic fibrosis (NSF) is a highly debilitating disorder primarily affecting the skin, but also other organ compartments. So far, it has only occurred in patients suffering from acute or chronic renal failure, with almost all of them having been exposed to gadolinium-based contrast agents (GBCA). The NSF registry was initiated on behalf of the German Society of Nephrology. The aim was to analyze the development, risk factors and clinical course of patients suffering from NSF. Patients and methods: Between July 2007 and July 2009, 23 patients were registered (12/23 (52,2%) male and 11/23 (47,8%) female). Onset of NSF symptoms was between 2002 and 2008, with a maximum of 8 cases in 2005. Since January 2008 no patient with a new onset of NSF has been reported. On all patients nuclear magnetic resonance procedures were performed between 1 day and 3 years (median 30 days) before the onset of symptoms (“index procedure”). At the time of the index procedure 21/23 (91,3%) patients required dialysis, 15/22 patients (68,2%) showed signs and symptoms of atherosclerosis and 17/20 (76,5%) of inflammation. 22/23 patients remained in chronic kidney disease stage 5D. Upper and lower extremities were affected in 18/23 (78,3%) patients; 20/23 (87%) developed joint contractures. Results: Our data confirm previous observations that NSF is associated with impaired renal function and the application of GBCA. In individual cases the interval between the index procedure and the onset of symptoms lasted years. Conclusion: The incidence of NSF has decreased rapidly within the past 4 years. This could be due to general awareness within the medical community and the application of macrocyclic chelates.Correspondence to:
Prof. Dr. A. Kribben
Department of Nephrology
University Duisburg-Essen
Hufelandstraße 55
45122 Essen, Germany
Email: [email protected]
Original
The effect of etanercept on suppression of the systemic inflammatory response in chronic hemodialysis patients
B.R. Don, K.Kim, J. Li, T. Dwyer, F. Alexander and G.A. Kaysen
Page No. 431
Abstract
The effect of etanercept on suppression of the systemic inflammatory response in chronic hemodialysis patients
B.R. Don1, K.Kim2, J. Li2, T. Dwyer1, F. Alexander1 and G.A. Kaysen1,3,4
1Division of Nephrology, University of California Davis School of Medicine and the UC Davis Medical Center, 2Division of Biostatistics, Department of Public Health Sciences, University of California Davis School of Medicine, 3Department of Biochemistry and Molecular Medicine, University of California, School of Medicine, Davis CA, and the 4Department of Veterans Affairs Northern California Health Care System, Mather, CA , USA
Background: Inflammation strongly predicts all-cause and cardiovascular mortality among dialysis patients. The negative acute-phase proteins, albumin and prealbumin are both inversely associated with mortality. Both albumin and prealbumin levels are decreased by inflammation. We carried out a pilot study to establish whether treatment with the tumor necrosis factor-α receptor antagonist etanercept would be safe and result in improved levels of albumin and prealbumin in inflamed hypoalbuminemic (albumin < 3.8 g/dl, CRP > 8.0 mg/l) prevalent hemodialysis patients. Methods: We excluded patients who had infectious risk (hepatitis C or B positive, HIV positive, purified protein derivative (PPD) positive or having a history of tuberculosis, having a tunneled dialysis catheter) to find patients having both hypoalbuminemia and inflammation. Of 433 less than 6% met the inclusion criteria. 10 patients were randomized to receive etanercept or placebo twice weekly for 44 weeks. Results: There were no adverse infectious events. There was no significant difference for any of the measurements between the two groups. However there was a significant difference in the time-dependent effects of etanercept on prealbumin: increasing 20% in the etanercept group while decreasing in the placebo group. Conclusions: Administration of a TNF-α receptor antagonist appears safe in this selected population, despite the large increase in infectious risk observed in the dialysis patient population. The effect on surrogate markers of inflammation is small. Correspondence to:
G.A. Kaysen MD, PhD
Division of Nephrology
Genome and Biomedical Sciences Facility
451 Health Sciences Drive
University of California
Davis, CA 95616, USA
Email: [email protected]
Original
Keratinocyte cancer prevention with ACE inhibitors, angiotensin receptor blockers or their combination in renal transplant recipients
L. Moscarelli, M. Zanazzi, G. Mancini, E. Rossi, L. Caroti, G. Rosso, E. Bertoni and M. Salvadori
Page No. 439
Abstract
Clinical Nephrology, Vol. 73 – No. 6/2010 (439-445)
Keratinocyte cancer prevention with ACE inhibitors, angiotensin receptor blockers or their combination in renal transplant recipients
L. Moscarelli, M. Zanazzi, G. Mancini, E. Rossi, L. Caroti, G. Rosso, E. Bertoni and M. Salvadori
Renal Unit Careggi University Hospital, Florence, Italy
Background: Skin cancer (SC) is the most frequent malignancy after renal transplantation (RT), especially squamous and basal cell carcinoma. The observation that angiotensin II is a potent angiogenic and growth factor raises the possibility that blocking its effects could reduce the incidence of skin cancer. Objectives: To evaluate the incidence of keratinocyte cancer in RT recipients, the timing of occurrence of the skin events after RT; to compare the incidence of SC in our RT recipients and in RT patients on angiotensin converting enzyme inhibitors (ACEi), angiotensin receptor blockers therapy (ARBs) and their combination. Risk factors were also evaluated. Results: During follow up, 52 of 565 patients (9.2%), 38 males 14 females, developed SC at a median time of 59 months (range 29 – 74) after RT. 12 of 52 patients (23%) with SC were on ACEi, ARBs therapy or their combination. The incidence was significantly lower in user patients compared to non user (5.6% and 11.4% respectively). BCC was the most frequent type of keratinocyte cancer in non users and in users. No association with incidence of BCC or SCC was observed for other classes of antihypertensive drugs (calcium antagonists, β-blockers, α-blockers). Conclusion: This study confirms that RT patients are at high risk of SC. The use of ACEi or ARBs is associated with an approximately two-fold reduced risk of Keratinocyte cancers compared to non users in RT recipients. We did not observe an association between the incidence of SC and the use of other classes of antihypertensive drugs. Any chemoprotective effect of these agents may reflect inhibition of the growth factor activity of angiotensin II. Use of ACEi or ARBs, when this is possible, should be considered in RT patients with multiple risk factors.Correspondence to:
Dr. L. Moscarelli
Renal Unit Careggi
University Hospital
Viale Pieraccini 18
50139 Florence, Italy
Email: [email protected]
Original
Recombinant human erythropoietin dosing errors due to concentrated EPO
D.M. Spiegel and R.A. Nemenoff
Page No. 446
Abstract
Clinical Nephrology, Vol. 73 – No. 6/2010 (446-448)
Recombinant human erythropoietin dosing errors due to concentrated EPO
D.M. Spiegel and R.A. Nemenoff
University of Colorado Denver Health Sciences Center, Denver, CO, USA
Aims: Recombinant human erythropoietin (rHuEPO) is widely used to treat anemia. A dialysis provider enacted a policy utilizing 20,000 U/ml multi-dose vials for rHuEPO dosing. The purpose of this study was to determine the accuracy and precision in administering small rHuEPO doses from this vial. Methods: Ten registered nurses (RNs) were selected at random, supplied with a rHuEPO vial refilled with water, and instructed to withdraw the following amounts (1,200 U, 2,400 U, 3,600 U) using standard procedures and assuming the standard rHuEPO concentration of 20,000 U/ml. Samples were drawn up in duplicate and placed into 1.5 ml micro-centrifuge tubes. The volumes were measured using P-100 or P-200 microliter pipettes. The equivalent amount of rHuEPO was calculated by multiplying the volume by 20 U/µl. Results: The rHuEPO dosing errors were large and on occasion greater than 100% at the 1,200 U dose. The variability for each RN, while large, was less than the inter-RN variability (within-RN % error 9.6% vs. 29.8% between-RN % error at the 1,200 unit dose). Errors occurred in both directions, both under- and overdosing. Conclusion: Utilizing concentrated rHuEPO resulted in significant dosing errors at low rHuEPO doses. The implications include inaccurate medication administration and disparity between administered and billed dosages. Policy decisions that effect medication administration need to be carefully evaluated to determine their impact on patient well-being and safety.Correspondence to:
D.M. Spiegel, MD
University of Colorado Denver HSC
4545 E. 9th Ave., Suite 160
Denver, CO 80220, USA
Email: [email protected]
Original
Peritoneal dialysis without a physical peritoneal dialysis unit
E.I. Grapsa, S. Klimopoulos, P. Tseke, N. Papaioannou and H. Tzanatos
Page No. 449
Abstract
Clinical Nephrology, Vol. 73 – No. 6/2010 (449-453)
Peritoneal dialysis without a physical peritoneal dialysis unit
E.I. Grapsa1, S. Klimopoulos2, P. Tseke1, N. Papaioannou1 and H. Tzanatos3
1Renal Unit, Alexandra Hospital, 2Department of Surgery, Evagelismos Hospital, and 3Department of Nephrology, Aretaieio University Hospital, Athens, Greece
Under certain circumstances when patients need peritoneal dialysis (PD) but no physical unit or official staff are available, one has to improvise ways to serve such patients. In this study we describe our experience with such patients without a physical peritoneal dialysis unit. Patients and methods: Since 1997 we trained 33 patients, mean age 61.7 ± 12.8 years old. Catheter implantation was done in another hospital on them as out-patients. We used trained nurses made available by the company that supplies the PD solution. After 2004 the whole training was done at patients’ home, after having been accepted by the patients. Results: Catheter implantation was successful in all 33 patients. Catheter was removed from 2 patients (one and 4 years after implantation) because of relapsing peritonitis in the first and fungal infection in the second. The overall peritonitis rate was 0.18 episodes/patient year or one episode every 63.5 patient months. Actuarial patient survival was 90%, at one year, 83% at second year and 55% at third year. First and second year technique survival were 96%, and 90% respectively. Conclusion: Our results, should encourage those who want to provide peritoneal dialysis to their patients even when a physical peritoneal dialysis unit is not available.Correspondence to:
Dr. E. Grapsa
Kousidou 97
15772 Athens, Greece
Email: [email protected]
Original
An aid to the diagnosis of genetic disorders underlying adult-onset renal failure: a literature review
H. Joosten, Strunk, S. Meijer, J.E. Boers, M.J.H. Ariës, A.P. Abbes, H. Engel and J.R. Beukhof
Page No. 454
Abstract
Clinical Nephrology, Vol. 73 – No. 6/2010 (454-472)
An aid to the diagnosis of genetic disorders underlying adult-onset renal failure: a literature review
H. Joosten1*, A.L.M. Strunk2, S. Meijer1, J.E. Boers3, M.J.H. Ariës4, A.P. Abbes2, H. Engel2 and J.R. Beukhof1
1Department of Internal Medicine and Nephrology, 2Department of Clinical Chemistry, 3Department of Pathology, Isala Clinics, Zwolle, The Netherlands, 4Department of Neurology, University Medical Center Groningen, Groningen, The Netherlands, *Currently: Department of Internal Medicine and Nephrology, University Medical Center Groningen, Groningen, The Netherlands
Several genetic disorders can present in adult patients with renal insufficiency. Genetic renal disease other than ADPKD accounts for ESRD in 3% of the adult Dutch population. Because of this low prevalence and their clinical heterogeneity most adult nephrologists are less familiar with these disorders. As a guideline to differential diagnosis, we provide an overview of the clinical manifestations and the pathogenesis of the main genetic disorders with chronic renal insufficiency surfacing in adulthood and add an algorithm plus 4 tables. We also indicate where molecular genetics nowadays can be of aid in the diagnostic process. The following disorders are discussed by mode of inheritance: 1) Autosomal dominant: autosomal dominant polycystic kidney disease, nephropathies associated with uromodulin (medullary cystic disease and familial juvenile hyperuricemic nephropathy), renal cysts and diabetes syndrome, nail-patella syndrome, glomerulopathy with fibronectin deposits. 2) Not autosomal dominant: Nephronophthisis, Fabry disease, primary oxalosis, Adenine Phosphoribosyl Transferase deficiency, Alport syndrome, Lecithin-cholesterol acyltransferase deficiency, adult-onset cystinosis.Correspondence to:
H. Joosten, MD
Department of Internal Medicine and Nephrology
University Medical Center
Hanzeplein 1
9700 RB Groningen, The Netherlands
Email: [email protected]
Case Report
A case of frequently relapsing nephrotic syndrome combined with Perthes disease
K. Mori
Page No. 473
Abstract
Clinical Nephrology, Vol. 73 – No. 6/2010 (473-477)
A case of frequently relapsing nephrotic syndrome combined with Perthes disease
K. Mori
Pediatric Department, Seirei Sakura Citizen Hospital, Sakura-shi, Japan
Orally-administered steroids often induce osteonecrosis of the femoral head. In cases of Perthes disease, osteonecrosis of the femoral head occurs in children due to an unknown cause. Our subject was a 4-year-old boy who had to be given large amounts of steroids because of frequently relapsing nephrotic syndrome (FRNS) developed after the onset of Perthes disease. One month earlier, he would limp with his right leg, but his radiographs were normal. Later, facial edema appeared and he was brought to our hospital with heavy proteinuria. He was diagnosed with NS and prescribed prednisolone for 2 months. As he would limp occasionally during the treatment, he had an orthopedic examination at our hospital, and shrinkage of the right femoral head was disclosed. Perthes disease was diagnosed on the basis of his MRI and clinical history. Meanwhile, NS relapsed twice over a half year, and he was diagnosed as having FRNS. Cyclophosphamide was administered for 12 weeks. Four years later, MRI indicated that the femoral head slowly improved and he was able to walk without prosthetic support. These results suggest that in the course of healing from Perthes disease, the conventional method of using prednisolone has little impact on the femoral head.Correspondence to:
K. Mori, MD
Seirei Sakura Citizen Hospital
2-36-2 Ebaradai, Sakura-shi
Chiba Prefecture, 285-8765 Japan
Email: [email protected]
Case report
Arterial dissections in autosomal dominant polycystic kidney disease – chance association or part of the disease spectrum?
N. Nacasch, M. Werner, E. Golan and Z. Korzets
Page No. 478
Abstract
Clinical Nephrology, Vol. 73 – No. 6/2010 (478-481)
Arterial dissections in autosomal dominant polycystic kidney disease – chance association or part of the disease spectrum?
N. Nacasch1, M. Werner2, E. Golan1,3 and Z. Korzets1,3
Departments of 1Nephrology and Hypertension, and 2Diagnostic Imaging, Ultrasound Unit, Sapir Medical Center, Kfar-Saba, and the 3Sackler Faculty of Medicine, Tel-Aviv University, Ramat-Aviv, Israel
Autosomal dominant polycystic kidney disease (ADPKD) has been associated with a number of vascular abnormalities of which the most widely known is intracranial aneurysm (Berry aneurysm). Arterial dissections involving both the thoracic and abdominal aorta, coronary, cervical and vertebral arteries have been anecdotally reported usually within the context of a medical emergency. As hypertension is a frequent early accompaniment of ADPKD (50 – 70% of nonazotemic patients) the occurrence of these dissections has commonly been attributed to hypertension. However, the question arises whether ADPKD patients have an inherited predisposition to the development of arterial dissections or are the latter alternatively part of the spectrum of extrarenal manifestations of ADPKD? We report the case of a 61-year-old woman with ADPKD on maintenance hemodialysis in whom asymptomatic dissection of the abdominal aorta was first suspected on a routine abdominal ultrasound performed as part of her pretransplantation checkup. A computed tomographic angiogram (CTA) showed the presence of polycystic kidney and liver disease and confirmed the existence of synchronous dissection of the left subclavian artery and the abdominal aorta beginning below the renal arteries and extending to the bifurcation and left common iliac artery. Although the patient was hypertensive, her blood pressure was well controlled on relatively mild antihypertensive medication. This case highlights the association of arterial dissection in ADPKD and provides the stage for discussing the question posed above.Correspondence to:
Prof. Ze’ev Korzets
Meir Hospital
Sapir Medical Center
Kfar-Saba, 44281, Israel
Email: [email protected]
Case Report
Two patients with focal segmental glomerulosclerosis complicated by Cyclosporine-induced reversible posterior leukoencephalopathy syndrome
N. Sakai, Y. Kawasaki, T. Imaizumi, S. Kanno, H. Go, M. Mitomo, Y. Ushijima, K. Suyama, M. Ito, K. Hashimoto and M. Hosoya
Page No. 482
Abstract
Clinical Nephrology, Vol. 73 – No. 6/2010 (482-486)
Two patients with focal segmental glomerulosclerosis complicated by Cyclosporine-induced reversible posterior leukoencephalopathy syndrome
N. Sakai, Y. Kawasaki, T. Imaizumi, S. Kanno, H. Go, M. Mitomo, Y. Ushijima, K. Suyama, M. Ito, K. Hashimoto and M. Hosoya
Department of Pediatrics, Fukushima Medical University School of Medicine, Fukushima City, Fukushima, Japan
Reversible posterior leukoencephalopathy syndrome (RPLS) is a distinctive clinicoradiological entity observed in a variety of clinical settings. Cyclosporine (CyA)-RPLS has been reported in a few patients with focal segmental glomerulosclerosis (FSGS); however, there had been no reports on developed RPLS after the re-administration of CyA treatment. We report two patients with FSGS who developed CyA-induced RPLS and summarize the results of a literature review for similar patients. The two patients with FSGS presented here were a 4-year-old boy and a 9-year-old boy, who presented with steroid-resistant nephrotic syndrome (NS) and were treated with CyA. The first patient developed CyA-induced RPLS at the 7th day after the start of CyA treatment, and the second patient at the 16th day after the re-start of CyA treatment. The two patients complained of a visual disorder and exhibited signs of a disturbance in consciousness and hypertension. Electroencephalography (EEG) examinations revealed a generalized slow wave pattern, and magnetic resonance imaging (MRI) disclosed an area of high signal intensity in the white matter. Subsequently, CyA was discontinued and neurological symptoms improved and recrudescence of RPLS did not occur. Our findings suggest that patients with FSGS and NS who are treated with CyA should be closely monitored for the possible onset of RPLS, presenting as a disturbance in consciousness, visual disturbances and/or convulsions.Correspondence to:
Y. Kawasaki, MD
1 Hikariga-oka
Fukushima City
Fukushima 960-1295, Japan
Email: [email protected]
Case Report
A female infant with Frasier syndrome showing splice site mutation in Wilms’ tumor gene (WT1) intron 9
S. Fujita, K. Sugimoto, T. Miyazawa, H. Yanagida, N. Tabata, M. Okada and T. Takemura
Page No. 487
Abstract
Clinical Nephrology, Vol. 73 – No. 6/2010 (487-491)
A female infant with Frasier syndrome showing splice site mutation in Wilms’ tumor gene (WT1) intron 9
S. Fujita, K. Sugimoto, T. Miyazawa, H. Yanagida, N. Tabata, M. Okada and T. Takemura
Department of Pediatrics, Kinki University School of Medicine, Osaka-Sayama, Japan
Wilms’ tumor gene (WT1) abnormality leads to various disorders of differentiation as well as renal and urinary system abnormalities. Here we present a case of WT1 abnormality and steroid-resistant nephrotic syndrome in a female infant. The 3-year-old patient was initially diagnosed with proteinuria at an annual mass screening program for children aged three years and was referred to our hospital. She met the diagnostic criteria for nephrotic syndrome and showed normal renal function. The patient was treated with corticosteroids; however her condition showed resistance to corticosteroids. On renal biopsy, she was diagnosed with focal segmental glomerulosclerosis (FSGS). Because of the possibility of WT1 abnormality, an exon array analysis was conducted, which ruled out Denys-Drash Syndrome (DDS). The patient was then diagnosed with Frasier Syndrome (FS) on the basis of donor site mutation (IVS9+5G > A) of the splice site in the intron 9. Reports of female infants with FS are extremely rare. FS is one of the pre-mRNA splicing diseases, in which the occurrence of symptoms is associated with a decrease in the ratio of the lysine-threonine-serine (± KTS) isoform of the WT1 protein. A typical case exhibits 46 XY male karyotype and is characterized by male pseudohermaphroditism with cord-like gonadal structures as well as progressive nephropathy caused by FSGS. However, in female infants without such extrarenal signs, it is necessary to consider the analysis for WT1 intron 9 for conclusive diagnosis of FS, because the presence of nephropathy is the only symptom for possible detection.Correspondence to:
T. Takemura, MD
PhD Department on Pediatrics
Kinki University School of Medicine
377-2 Ohno-higashi
Osaka-Sayama, 589-8511, Japan
Email: [email protected]
Letter to the Editor
Systemic sclerosis sine scleroderma sine hypertension presenting as nephrotic syndrome
S. Chung, J.Y. Kim, Y.-A. Hong, S.H. Gil, J. Yu, J.C. Song, Y.S. Chang and C.W. Park
Page No. 492
Abstract
Systemic sclerosis sine scleroderma sine hypertension presenting as nephrotic syndrome
S. Chung1, J.Y. Kim1,2, Y.-A. Hong1,2, S.H. Gil1,2, J. Yu1,2, J.C. Song1, Y.S. Chang1 and C.W. Park2
1Division of Nephrology, St. Mary’s Hospital, and 2Division of Nephrology, Seoul St. Mary’s Hospital, The Catholic University of Korea, Seoul, Republic of Korea
