Volume 72, No. 1/2009(July)
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 Clinical Nephrology
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Editorial
My best wishes for the future of “Clinical Nephrology”!
Editorial
Many thanks and Goodbye to Professor Koch – welcome to Professor Malluche!
Abstract
J. Feistle and F. Feistle
Editorial
“Tempora mutantur et nos mutamur in illis” – “Times are changing, and so are we”
Abstract
H.H. Malluche and B.P. Sawaya
Lead Article
The five most commonly used intact parathyroid hormone assays are useful for screening but not for diagnosing bone turnover abnormalities in CKD-5 patients
Abstract
J. Herberth1, M.-C. Monier-Faugere1, H.W. Mawad1, A.J. Branscum2, Z. Herberth1, G. Wang1, T. Cantor3 and H.H. Malluche1
1Division of Nephrology, Bone and Mineral Metabolism, University of Kentucky, 2Departments of Biostatistics, Statistics, and Epidemiology, University of Kentucky, Lexington, KY, and 3Scantibodies Laboratory, Inc., Santee, CA, USA
Background/Aims: Assessment of bone turnover for management of renal osteodystrophy is part of routine care in chronic kidney disease Stage 5 (CKD-5) patients. Measurement of intact parathyroid hormone (iPTH) is the most commonly used surrogate marker for bone turnover in these patients. The current study was conducted to evaluate the predictive value of the five most commonly used iPTH assays for bone turnover. Methods: In a cross-sectional study, 84 CKD-5 patients underwent bone biopsy and blood drawings for determination of iPTH and total serum alkaline phosphatase (AP). Results: Histologically, patients presented with a broad range of bone turnover abnormalities as determined by activation frequency and bone formation rate/bone surface. Results of the five iPTH assays in each patient correlated but were significantly different. There were also significant differences between iPTH measurements at the same bone turnover level. Using Kidney Disease Outcome Quality Initiative recommended iPTH ranges, all assays showed comparably poor diagnostic performance. At 80% specificity, cut-off values of the 5 iPTH assays for low bone turnover varied from 165 to 550 pg/ml and for high bone turnover from 404 to 1,003 pg/ml. Sensitivities at these cutoffs remained below acceptable standards. Addition of AP measurements to iPTH did not improve diagnostic accuracy. Conclusions: Precise assessment of bone turnover will require utilization of established and novel bone markers reflecting effects of bone turnover rather than measuring only iPTH or other effectors.Correspondence to:
H.H. Malluche, MD
Division of Nephrology, Bone and Mineral Metabolism
University of Kentucky
800 Rose Street MN564
Lexington, KY 40536-0298, USA
Email: hhmall@uky.edu
Original
The relationship between chronic hepatitis B infection and bone mineral, metabolism in peritoneal dialysis patients
Abstract
Y.-L. Liu1,2, S.-M. Wang1, H.-H. Lin1,2, I-K. Wang1, H.-L. Kuo1,2, Y.-F. Yang1, J.-H. Liu1, C.-Y. Chou1, H.-C. Yeh1, I-W. Ting1, C.-A. Tsai3 and C.-C. Huang1
1Division of Nephrology and Kidney Institute, Department of Medicine, China Medical University Hospital, 2Graduate Institute of Clinical Medical Science, China Medical University and 3Department of Public Health, China Medical University, Taichung, Taiwan
Objective: Abnormality of bone mineral metabolism is a common complication in chronic liver disease and/or chronic renal disease patients. We designed this study to evaluate the relationship between chronic hepatitis B infection and bone mineral metabolism in peritoneal dialysis patients. Patients and methods: Serum calcium[adj], phosphorus, calcium and phosphorus product (Ca × P), along with intact parathyroid hormone (iPTH) levels were compared in peritoneal dialysis patients with and without chronic hepatitis B infection. Results: A total of 220 patients (142 female, 78 male) with a mean age of 56.30 ± 14.28 (range 19 – 86) years old were recruited, 23 showed chronic hepatitis B infection and 197 showed none. No statistically significant difference in serum calcium[adj] levels (9.90 ± 0.85 mg/dl vs. 10.08 ± 0.80 mg/dl, p = 0.354), phosphorus levels (5.26 ± 1.58 mg/dl vs. 5.21 ± 1.35 mg/dl, p = 0.879) and calcium and phosphorus product (Ca × P) (52.23 ± 17.54 mg2/dl2 vs. 52.42 ± 14.16 mg2/dl2, p = 0.960) between groups with and without chronic hepatitis B infection was observed. Serum iPTH levels were significantly lower in chronic hepatitis B patients (median 143 pg/ml, range 3.42 – 889) than in the control group (median 235 pg/ml, range 3 – 2381) (p = 0.035). As analyzed by multi-variable linear regression, chronic hepatitis B was a predictor of lower serum iPTH levels (beta = –0.271; p = 0.030) after adjustments for age, gender, serum calcium and phosphorus levels and diabetes. Conclusion: No significant difference in serum calcium[adj]), phosphorus and calcium and phosphorus product (Ca × P) levels appeared between peritoneal dialysis patients with and without chronic hepatitis B infection. Serum iPTH levels proved to be definitely lower in chronic hepatitis B infection patients.Correspondence to:
C.-C. Huang, MD
Division of Nephrology and Kidney Institute
Department of Medicine, China Medical University
Hospital, No.2, Yu-der Rd., North District
Taichung City 404, Taiwan
Email: cch@www.cmuh.org.tw
Original
Plasma adiponectin concentration has an inverse and a non linear association with estimated glomerular filtration rate in patients with K/DOQI 3 – 5 chronic kidney disease
Abstract
P.W.B. Nanayakkara1,2, C.Y. Le Poole1,3, D. Fouque4, C. van Guldener5, C.D.A. Stehouwer6, Y.M. Smulders1,2, F.J. van Ittersum3, C.E.H. Siegert7, J. Drai8, P.J. Kostense9 and P.M. ter Wee4
1Department of Internal Medicine, 2Institute for Cardiovascular Research, 3Department of Nephrology, VU University Medical Center, Amsterdam, The Netherlands, 4Département de Néphrologie, University Claude Bernard, Lyon, France, 5Department of Internal Medicine, Amphia Hospital, Breda, 6Department of Medicine, University Hospital Maastricht, Maastricht, 7Department of Nephrology, St. Lucas Andreas Hospital, Amsterdam, The Netherlands, 8Biochemistry, Centre Hospitalier Lyon Sud, France, 9Clinical Epidemiology and Biostatistics, VU University Medical Center, Amsterdam, The Netherlands
Background: Chronic kidney disease (CKD) is associated with an increased incidence of cardiovascular disease (CVD). A few studies have demonstrated elevated plasma adiponectin and leptin levels in CKD. The aims of this study were to assess whether 1) estimated glomerular filtration rate (eGFR) is associated with plasma leptin and adiponectin; and 2) adiponectin and leptin (partly) explain associations of CKD with endothelial dysfunction, insulin resistance, and low-grade inflammation in patients with K/DOQI Stage 3 – 5 CKD. Methods: Baseline data from 91 patients with Stage 3 – 4 CKD in the anti-oxidant therapy in chronic renal insufficiency study, a randomized, double-blind, placebo-controlled trial, in which the effects of oxidative stress-lowering treatment on vascular function and structure were studied, and from 50 dialysis naïve patients, who took part in an open-label, randomized study that compared two peritoneal dialysis regimens, used in the analysis. All subjects for both the studies were recruited in the same centres. Results: The association between eGFR and adiponectin was non-linear. In multivariate analysis, log-eGFR (unstandardized beta = ¯8.303 µg/ml, p < 0.0001) was the strongest determinant of adiponectin, and body mass index the strongest determinant of leptin (beta = 2.477 ng/ml, p < 0.0001). Plasma adiponectin and leptin did not modify the associations between eGFR and plasma von Willebrand factor or soluble vascular adhesion molecule-1. Plasma leptin had the strongest association with the homeostatic model assessment (HOMA-IR) index. Plasma C-reactive protein had no association with adiponectin or leptin. Conclusions: In patients with K/DOQI Stage 3 – 5 CKD, renal function had a significant non-linear inverse association with and was the strongest predictor of adiponectin. BMI was the strongest predictor of plasma leptin. Plasma adiponectin and leptin did not explain, and thus presumably are not involved in, the association between eGFR and some markers of endothelial dysfunction.Correspondence to:
Dr. P.W.B. Nanayakkara, MD
Department of Internal Medicine
VU University Medical Center
PO Box 7057
1007 MB Amsterdam
The Netherlands
Email: p.nanayakkara@vumc.nl
Original
Mycophenolate mofetil as maintenance therapy in patients with vasculitis and renal involvement
Abstract
C. Iatrou1, S. Zerbala1, I. Revela1, E. Spanou1, S. Marinaki2, L. Nakopoulou3 and J. Boletis2
1Center for Nephrology “G. Papadakis”, General Hospital of Nikea, Nikea, Pireaus, 2Department of Nephrology, Laiko Hospital, and 3A’ Department of Pathology, Athens National University Medical School, Athens, Greece
Aim: Cytotoxic drugs have reduced the mortality in patients with ANCA-associated vasculitis (AASV) but their use carries a substantial risk of toxicity. Efforts are made to switch from cytotoxic drugs to less toxic maintenance regimens. In this study we aimed to assess the efficacy of mycophenolate mofetil (MMF) as maintenance therapy in patients with AASV and renal involvement. Methods: 22 patients with newly diagnosed AASV, microscopic polyangiitis (MPA) (n = 16), Wegener’s granulomatosis (WG, n = 4), renal limited vasculitis (RLV, n = 1) and Churg-Strauss syndrome (CSS, n = 1) and renal involvement were followed for a median of 42 months (range 24 – 101). After 6 months of standard induction therapy, patients were switched to MMF monotherapy for 18 months. Renal parameters i.e. serum creatinine, proteinuria and urine sediment, BVAS scores and ANCA titers were assessed at baseline, after induction and after 18 months with MMF. Results: After the end of induction, 3 of the 4 patients who were initially hemodialysis (HD) dependent, remained on HD and were withdrawn from further analysis. In the remaining 19 patients, the improvement in renal function (p < 0.001), hematuria (p = 0.011), proteinuria (p = 0.007) and BVAS scores (p < 0.001) after induction was sustained after 18 months maintenance with MMF and no patient relapsing during this period. Until the end of the follow up, 31.58% of patients relapsed, at a median of 21.5 months (range: 18 – 60). Side effects were transient and infrequent. Conclusion: In patients with AASV and renal involvement, MMF seems to be an effective and well tolerated option in sustaining short- and medium-term remission.Correspondence to:
C. Iatrou, MD
Amaryssias Artemidos 32-34
K.A 151-24 Maroussi, Athens, Greece
Email: ciatroug@otenet.gr
Original
Glomerular lesions in HIV-positive patients: a 20-year biopsy experience from Northern Italy
Abstract
M. Nebuloni1, G. Barbiano di Belgiojoso2, A. Genderini2, A. Tosoni1, N. Landriani2, M. Heidempergher2, P. Zerbi1 and L. Vago1
1Pathology Unit, “L. Sacco” Department Clinical Sciences and 2 Nephrology Unit, “L.Sacco” Hospital, University of Milan, Milan, Italy
Aim: Glomerular involvement in HIV-positive patients is quite heterogeneous. In the present paper we reviewed 73 renal biopsies performed during a period of more than 20 years in a single Nephrology Unit, Milan, Northern Italy, in order to evaluate the aspects of single types of glomerular lesions (including HIV associated nephropathy-HIVAN), grouped according to histological patterns and clinical presentation. Moreover, in the group of non-HIVAN patients, the possible differences in histological characteristics from non-HIV lesions were investigated. Materials and methods: Renal tissues were obtained by percutaneous biopsies and were studied by light microscopy, immunofluorescence and electron microscopy. For the histological description three histological groups were identified: HIVAN, immune complex glomerulonephritis (GN) and glomerulopathies not related to immune-mediated mechanisms (so-called “various” glomerulopathies). Results: HIVAN was observed in 9 cases, immune complex GNs in 40 cases (10 mesangial proliferative GN, 8 membranoproliferative GN, 5 lupus-like GN, 4 “acute” GN, 2 crescentic GN, 4 IgA nephropathy, 4 membranous GN and 3 immunotactoid GN) and “various” glomerulopathies in 24 cases (13 non-collapsing focal segmental glomerulosclerosis, 3 minimal changes, 3 end-stage renal disease, 4 diabetic nephropathy and one amyloidosis). Conclusions: Our 20-year biopsy series of HIV-related glomerular involvement confirmed the heterogeneity of lesions. In our series, the vast majority of HIV-related GN are the so-called immune complex GNs, with some peculiar aspects, as multiple site location of deposits and a frequent tendency towards sclerosis, in agreement with experimental data regarding HIV and fibrosis.Correspondence to:
M. Nebuloni, MD
Pathology Unit, “L. Sacco” Dept. Clinical Sciences
University of Milan, “L.Sacco” Hospital
Via G.B. Grassi 74, 20157 Milan, Italy
Email: manuela.nebuloni@unimi.it
Original
Characteristics of proliferative glomerulo-nephritis with monoclonal IgG deposits associated with membranoproliferative features
Abstract
R. Masai1, H. Wakui1, A. Komatsuda1, M. Togashi1, N. Maki1, H. Ohtani2, Y. Oyama3 and K. Sawada1
1Third Department of Internal Medicine, Akita University School of Medicine, 2Department of Nephrology and Dialysis, Akita Kumiai General Hospital, Akita, and 3Department of Internal Medicine, Municipal Sakata Hospital, Sakata, Japan
Background: Proliferative glomerulonephritis with monoclonal IgG deposits (PGNMID) associated with membranoproliferative features is an extremely rare entity. Information on clinicopathological features and prognosis in this entity is limited. Methods: We reviewed 5,443 renal biopsies processed at our department, and identified 4 patients with PGNMID associated with membranoproliferative features. We evaluated clinicopathological features and outcomes in these patients, and characterized paraprotein deposits by immunofluorescence studies. Results: Three out of 4 patients had nephrotic syndrome with renal insufficiency at presentation. Cryoglobulin or monoclonal protein in serum and urine was not detected. Renal biopsy showed membranoproliferative features with or without nodular formation. Tubulointerstitial and vascular alterations were mild in three patients. All patients had glomerular IgG-kappa deposits. Heavy chain subclass analysis performed in 3 patients showed IgG3 deposits. Immunofluorescence studies using antibodies specific for gamma-heavy chain CH1, CH2, and CH3 domains and gamma3 hinge did not show any apparent deletion. Confocal microscopy revealed glomerular colocalization of light and heavy chains. On electron microscopy, granular deposits were predominantly mesangial and subendothelial. All patients were treated with steroids and cytotoxic agents, but no effect on proteinuria was observed. The renal outcome was progressive in all patients. Early death was observed in two elder patients. No patient had overt myeloma or lymphoma at presentation or over the course of follow-up (mean 43 months). Conclusions: Our study suggests a predominance of IgG3-kappa glomerular deposits of nondeleted whole immunoglobulin molecules in PGNMID associated with membranoproliferative features. The clinical outcome in patients with this entity appears to be poor.Correspondence to:
H. Wakui, MD
Third Department of Internal Medicine
Akita University School of Medicine
1-1-1 Hondo, Akita City, Akita 010-8543, Japan
Email: wakui@med.akita-u.ac.jp
Original
Long-term outcome of single pediatric donor kidney transplants between African-American and non-African-American adults
Abstract
A. Paramesh1, R. Zhang2, C.L. Yau3, S. Balamuthusamy2, R. Shenava2, M. Killackey1, B. Alper2, E. Simon2, D. Slakey1 and S. Florman1
Departments of 1Surgery and 2Medicine, School of Medicine, Department of 3Biostatistics, School of Public Health and Tropic Medicine, Tulane University, New Orleans, LA, USA
Background: African-American (AA) ethnicity has been considered a risk factor for graft loss after kidney transplant. The long-term graft survival of single pediatric donor kidney transplants in AA adults has not been reported. Methods: We retrospectively compared the outcome of 43 AA and 32 non-African-American (NAA) adults transplanted with single pediatric kidneys from donors aged 10 years or less in our center. A combination of tacrolimus, mycophenolic acid and steroid was utilized as the maintenance therapy. Results: Similar immunosuppressive dose and targeted level were achieved between the AA and the NAA groups. Median body weight (BW) of donors was 20 kg (8 – 36) in the AA group and 19 kg (8.5 – 35) in NAA group. There was no statistically significant difference in the incidence of rejection between the AA and NAA groups (26 vs. 16%, p = 0.45). The surgical complications, delayed graft function, and development of proteinuria and focal and segmental glomerulosclerosis (FSGS) were similar in both groups. The patient and graft survivals in the AA group were slightly higher compared to the NAA group. The death-censored analysis demonstrated no difference in graft survival between the AA and NAA groups (p = 0.90): 86 vs. 82% at 1 year, 70 vs. 71% at 3 years, and 62 vs. 64% at 5 years. Conclusions: Single pediatric donor kidney transplant in AA adults can be achieved with acceptable complications and equivalent long-term outcomes as in NAA adults in the era of potent immunosuppressive regimen.Correspondence to:
R. Zhang, MD
FASN
1415 Tulane Ave, TW-35
New Orleans, LA 70112, USA
Email: rzhang@tulane.edu
Original
Influence of dialysis modality on renal transplant complications and outcomes
Abstract
Q. Yang1, S. Zhao1, W. Chen1, H. Mao1, F. Huang1, Z. Zheng1, L. Chen2, J. Fei2 and X. Yu1
1Department of Nephrology, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou and 2Department of Organ Transplantation, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, PR China
Aims: The present study investigated the influence of the pretransplant dialysis modality, hemodialysis (HD) or peritoneal dialysis (PD), on renal transplant complications and outcomes. Methods: 402 cadaveric renal transplant patients maintained on HD (N = 303) or PD (N = 99) for more than 3 months prior to transplantation were studied retrospectively, and a total of 345 patients were followed up for 30.2 ± 15.2 months. The impact of HD or PD on acute rejection, delayed graft function (DGF), infection, chronic rejection, and the survival rate of graft and patients were analyzed. Results: There was no significant difference between the HD and PD groups with regard to the causes of end-stage renal disease, age, gender, blood pressure, hemoglobin, HLA match, hot and cold ischemia time, and hepatitis C virus infection. The incidence rates of DGF, acute rejection, chronic rejection and cytomegalovirus and other infections were also not significantly different between the HD and PD groups. However, compared to HD, patients with PD had longer dialysis duration (p < 0.05), but less hepatitis B infection (p < 0.05) and post-transplant infection (p < 0.05). In contrast, in those PD patients with hepatitis B infection, graft loss was significantly increased (19.23% vs. 8.86% , p = 0.021). The incidence of acute rejection episodes was higher in HD patients who had pretransplant dialysis for more than 12 months (p < 0.05). The overall patient and graft survival rates within 5 years between the HD and PD groups were not significantly different (p > 0.05). Conclusions: The influence of PD and HD on complications after renal transplant at 1 year and 5 years and graft survival rates was similar, and therefore, either HD or PD can be chosen as the pretransplant dialysis modality. However, patients in the PD group had a reduced incidence of hepatitis virus infection, suggesting that PD may have certain advantages over HD as a preoperative substitution therapy for renal transplantation.Correspondence to:
X. Yu, MD, PhD
Department of Nephrology
The First Affiliated Hospital
Sun Yat-sen University
Guangzhou 510080, China
Email: yuxq@mail.sysu.edu.cn
Case Report
Successful therapeutic use of a single-dose of rituximab on relapse in adults with minimal change nephrotic syndrome
Abstract
Y. Sawara, M. Itabashi, C. Kojima, H. Tabata, D. Kamei, K. Kawanishi, T. Moriyama, H. Sugiura, M. Tsukada, T. Takei, T. Ogawa, T. Yoshida, J. Arai, K. Uchida, K. Tsuchiya and K. Nitta
Department of Medicine, Kidney Center, Tokyo Women’s Medical University, Tokyo, Japan
Minimal change nephrotic syndrome (MCNS) usually is considered to have a good renal prognosis, but the frequency of relapses is a therapeutic challenge to physicians. The treatment of patients with multiple relapses remains a matter of controversy, because few controlled studies are available. We report the case of a 25-year-old man who experienced relapses of MCNS. Single-dose rituximab therapy (total dose 500 mg) was given during the fourth relapse. Complete remission occurred 10 days later, when no CD19/20-positive B cells were detected in the blood. This the first report of efficacy of single-dose rituximab therapy to treat multi-relapsing MCNS in an adult patient.Correspondence to:
T. Takei, MD, PhD
Department of Medicine
Kidney Center
Tokyo Women’s Medical University
8-1 Kawada-cho
Shinjuku-ku, Tokyo 162-8666, Japan
Email: ttakei@kc.twmu.ac.jp
Case Report
Sunitinib treatment in patients with severe renal function impairment: a report of four cases by the Hellenic Cooperative Oncology Group
Abstract
G. Lainakis1, A. Bamias1, E. Psimenou1, G. Fountzilas2 and M.A. Dimopoulos1
1Department of Clinical Therapeutics, University of Athens, Medical School, Athens, and 2Department of Medical Oncology, Papageorgial Hospital, School of Medicine, Aristotle University, Thessaloniki, Greece
Sunitinib is approved for the treatment of metastatic renal cell carcinoma (RCC). No data are available on sunitinib use specifically in patients with significantly impaired renal function. We evaluated the safety and efficacy of sunitinib in patients with advanced RCC and Grade 4 renal function impairment. Four patients had a calculated creatinine clearance of 15 – 29 ml/min/1.73 m2 prior to initiation of sunitinib. Three patients tolerated treatment well with no renal toxicity: 2 received 17 and 5 cycles of sunitinib at full dose, while 1 received 5 cycles with a dose reduction due to myelotoxicity. We observed one partial response and two patients had stable disease for 24 and 4 months, respectively. The 4th patient had a creatinine clearance of 18 ml/min/1.73 m2 and had treatment discontinued during the first cycle due to poorly controlled hypertension and deterioration of his renal function. We conclude that sunitinib can be administered to the majority of patients with RCC and significant renal function impairment.Correspondence to:
A. Bamias, MD, PhD
57A Taygetou st, Vrilissia
Athens 152 35, Greece
Email: abamias@med.uoa.gr
Case Report
Acute renal failure due to amiodarone-induced hypothyroidism
Abstract
R. Luciani, C. Falcone, F. Principe, G. Punzo and P. Menè
Department of Nephrology, Sant’Andrea University Hospital, University of Rome “La Sapienza”, Rome, Italy
Renal alterations in hypothyroidism include decreased glomerular filtration rate and renal plasma flow. We herein report a case of amiodarone -induced hypothyroidism associated with a rapid decrease of renal function, reversible upon amiodarone withdrawal. A 72-year-old man presented to our clinic in August 2007 reporting a recent deterioration of renal function. Ten weeks before he was admitted to another hospital for a supraventricular tachyarrhythmia treated with carvedilol 12.5 mg/day and amiodarone 400 mg/day. On admission, laboratory tests revealed altered renal function (serum creatinine 6 mg/dl, blood urea nitrogen 78 mg/dl) and severe hypothyroidism (free T4 0.27 pg/ml, free T3 1.49 pg/ml, TSH 183.36 mU/l). Amiodarone and carvedilol were stopped, while levothyroxine 75 mcg/die was started. After three months renal function had completely recovered to 1.9 mg/dl, BUN 28 mg/dl, with concurrent improvement of thyroid function free T4 14.2 pg/ml, free T3 6.4 pg/ml, TSH 15.5 mU/l.Correspondence to:
Dr. R. Luciani
Department of Nephrology
Sant’Andrea Hospital
University of Rome “La Sapienza”
Via di Grottarossa 1035-1039
00189 Rome, Italy
Email: rluciani@ospedalesantandrea.it
Letter to the Editor
Low magnesium status and diabetes mellitus and hypertension
Abstract
K. Kisters, M.Q. Nguyen, B. von Ehrlich, D.H. Liebscher and M. Hausberg
Errata
