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Abstract

N.J. Hepburn, M.M. Ruseva, C.L. Harris and B.P. Morgan

Department of Medical Biochemistry and Immunology, School of Medicine,
Cardiff University, Cardiff, UK
The complement system, an essential part of the innate immune system, defends the host against invading pathogens, prevents immune complex disease and aids the acquired immune response. Under normal conditions the host is protected from complement attack by an array of complement regulatory proteins. However, in certain contexts inappropriate complement activation can occur associating the C system with a variety of disease pathologies. This review focuses upon the role complement plays in a number of renal pathologies as well as the role of complement in three examples of extrarenal diseases: paroxysmal nocturnal hemoglobinuria, age-related macular degeneration and liver fibrosis. From the evidence discussed it is clear that mutations or polymorphisms in the complement regulators resulting in reduced levels or inefficient action dramatically enhance susceptibility to certain diseases and in particular render the kidney more vulnerable to complement attack. Additionally, deficiency in the complement components can predispose to disease through reduced clearance of apoptotic cells and subsequent generation of complement activating autoantibodies or enhanced formation of convertases resulting in heightened complement activation. As complement has devastating effects, in such disease contexts it has become a therapeutic target. Therapeutic intervention strategies discussed here focus upon the use of recombinant agents, the most promising of which are the anti-C5 antibody-derived reagents. These agents have proved effective in the treatment of paroxysmal nocturnal hemoglobinuria, nephritis and ischemia-reperfusion injuries and will no doubt, along with other reagents currently being developed, prove invaluable in the treatment of renal pathologies.Correspondence to:
N.J. Hepburn, PhD; Department of Medical Biochemistry and Immunology, Henry Wellcome Building, School of Medicine, Cardiff University,
Heath Park, Cardiff, CF14 4XN, UK
Email: hepburnnj@cardiff.ac.uk

Abstract

S. Prakash¹,², T. Kanjanabuch³,⁴, P.C. Austin⁵,⁶, R. Croxford⁵, C.-Y. Hsu¹, A.I. Choi¹ and D.C. Cattran²,⁶

¹University of California, San Francisco, CA, USA, ²University Health Network, Toronto, Canada, ³King Chulalongkorn Memorial Hospital, ⁴Chulalongkorn University, Bangkok, Thailand, ⁵Institute for Clinical Evaluative Sciences and ⁶University of Toronto, Canada
Background/Aims: Local variations in patient demographics and medical practice can contribute to differences in renal outcomes in patients with IgA nephropathy. We report the experiences of two groups of Asians with IgA nephropathy across continents. Materials and methods: We retrospectively examined two cohorts of Asian patients with IgA nephropathy from The King Chulalongkorn Memorial Hospital registry, Thailand (1994 – 2005), and The Metropolitan Toronto Glomerulonephritis registry, Canada (1975 – 2006), and compared their baseline characteristics. Slope of estimated glomerular filtration rate (eGFR) in each group was approximated using separate repeated measures regression models for each country. Results: There were 152 Canadian and 76 Thai patients. At the time of first presentation, Thai patients were more likely to be female (63.2 vs. 44.1%, p = 0.01), have less baseline proteinuria (1.2 vs. 1.7 g/d, p = 0.08) and more likely to receive angiotensin-converting enzyme inhibitors (ACE-I) or angiotensin receptor blockers (ARB) (64.0 vs. 15.2%, p < 0.01), or prednisone (41.3 vs. 4.6%, p < 0.01). The annual change in estimated glomerular filtration rate (eGFR) for the Thai and Canadian groups were –0.82 ml/min/1.73 m²/year and –3.35 ml/min/1.73 m²/year, respectively, after adjustment for age, sex, mean arterial pressure (MAP), proteinuria, body mass index, Haas histological grade, chronicity scores and baseline medications. Conclusions: Although disease severity was similar among IgA nephropathy patients in Canada and Thailand, more Thai patients were on ACE-I/ARB or prednisone therapy at baseline. Further prospective research is needed to explore international differences in demographic and environmental factors, health resources, and disease management to determine how they may impact long-term outcomes in Asians with IgA nephropathy.Correspondence to:
Dr. S. Prakash; University Health Network, University of Toronto, EN-14th Floor, Room 216, 200 Elizabeth Street, Toronto, ON, M5G2C4, Canada
Email: suma.prakash@utoronto.ca

Abstract

T. Nakamura¹, T. Inoue², N. Fujiwara¹, Y. Kawagoe¹, T. Sugaya³, Y. Ueda⁴, H. Koide⁵ and K. Node²

¹Department of Internal Medicine, Shinmatsudo Central General Hospital, Chiba, ²Department of Cardiovascular and Renal Medicine, Saga University Faculty of Medicine, Saga, ³Research Unit for Organ Regeneration, Riken Kobe Institute, Hyogo, ⁴Department of Pathology, Koshigaya Hospital, Dokkyo University School of Medicine, Saitama, ⁵Department of Medicine, Koto Hospital, Tokyo, Japan
Azelnidipine has been reported to have antioxidant effects and attenuates tubulointerstitial ischemia. The aim of the present study was to determine whether azelnidipine exerts additional renoprotective effects to angiotensin II receptor blockers (ARBs) in hypertensive patients with diabetic nephropathy and microalbuminuria. 45 hypertensive patients with diabetes mellitus and microalbuminuria who were already being treated with ARBs were enrolled in this study. Azelnidipine was added to the drug treatment of 30 patients (8 mg/day, n = 15, or 16 mg/day, n = 15) whilst the remaining 15 control patients were not treated with azelnidipine. In all patients, urinary 8-hydroxydeoxyguanosine (8-OHdG) levels and urinary liver-type fatty acid-binding protein (L-FABP) levels were significantly correlated (r = 0.587, p = 0.0006). However, urinary albumin excretion (UAE) was not correlated with the levels of urinary 8-OHdG (r = 0.1975, p = 0.2956) or urinary L-FABP (r = 0.2057, p = 0.2759). Azelnidipine significantly reduced UAE, urinary 8-OHdG and urinary L-FABP after 6 (p < 0.05) and 12 months (p < 0.05). Although blood pressure was comparable between the azelnidipine doses of 8 and 16 mg/day, the UAE (p < 0.05 after 12 months), urinary 8-OHdG (p < 0.05 after 6 and 12 months) and urinary L-FABP (p < 0.05 after 6 and 12 months) levels were more significantly reduced in patients receiving the higher dose of 16 mg/day. These data may suggest that the addition of azelnidipine treatment to therapy with ARBs has dose-dependent antioxidant and renoprotective effects beyond blood pressure-lowering effects in hypertensive diabetic nephropathy patients.Correspondence to:
T. Inoue, MD; Department of Cardiovascular and Renal Medicine, Saga University Faculty of Medicine, 5-1-1, Nabeshima, Saga 849-8501, Japan
Email: inouete@med.saga-u.ac.jp

Abstract

T. Sato¹, M. Fujieda¹, A. Maeda¹, E. Tanaka², M. Miyamura², H. Chikamoto², M. Hisano², Y. Akioka², Y. Ishiura¹, S. Dohno¹, M. Hattori² and H. Wakiguchi¹

¹Department of Pediatrics, Kochi Medical School, Kochi University, Kochi, and ²Department of Pediatric Nephrology, Kidney Center, Tokyo Women’s Medical University, School of Medicine, Tokyo, Japan
Aim: The aim of this study is to establish a monitoring method to prevent Epstein-Barr virus (EBV)-associated symptoms including post-transplant lymphoproliferative disorder (PTLD) that occur after pediatric renal transplantation. Subjects and methods: Circulating EBV loads were quantified by real-time PCR every 1 – 3 months after grafting in 22 pediatric recipients (13 EBV-seronegative [R(–)] and 9 EBV-seropositive [R(+)] recipients before grafting). The peripheral blood cell populations of non-specific activated killer cells (CD8⁺HLA-DR⁺ phenotype) in 13 R(–) recipients and EBV-specific cytotoxic T cells (CTLs) reactive with a tetramer expressing HLA-A24-restricted EBV-specific antigens in 8 of 13 R(–) recipients were determined by flow cytometry. Results: EBV-associated symptoms including PTLD (2 cases) were found in 4 R(–) and none of the R(+) recipients. The maximum of EBV load in the R(–) group was significantly higher that in the R(+) group. In R(–) recipients, 4 symptomatic cases had significantly more EBV genome than asymptomatic cases. EBV-specific CTLs were detected in 6 of the 8 R(–) recipients, but these CTLs could not be detected in 1 of the 2 cases at onset of PTLD. The percentage of CD8⁺HLA-DR⁺ cells was significantly higher in asymptomatic recipients than in recipients with EBV-associated symptoms whose EBV loads were over 400 copies/µg DNA. Conclusion: Monitoring of killer T cells and EBV loads may allow assessment of the risk of EBV-associated symptoms, and high EBV loads and low EBV-specific and/or non-specific CTL responses may be predictive for development of EBV-associated symptoms such as PTLD.Correspondence to:
M. Fujieda, MD; Department of Pediatrics, Kochi Medical School, Kochi University, Kohasu, Oko-cho, Nankoku, Kochi 783-8505, Japan
Email: fujiedam@kochi-u.ac.jp

Abstract

T. Shigematsu¹ and the Lanthanum Carbonate Group

¹Division of Nephrology and Blood Purification Medicine, Department of Medicine, Wakayama Medical University, School of Medicine, Wakayama City, Japan
Background: The efficacy of lanthanum carbonate as a phosphate binder for the treatment of hyperphosphatemia has been reported, but not from a double-blind, comparator-controlled comparative study. Methods: The safety and efficacy of lanthanum carbonate and calcium carbonate on serum phosphate and calcium levels in Japanese hemodialysis patients were assessed by a randomized, double-blind, comparator-controlled, parallel group, multicenter study. This study is the first study using a randomized, double-blind method to compare lanthanum carbonate and calcium carbonate as phosphate binders. Results: In the double-blind phase, the changes in the serum phosphate level were similar in the lanthanum carbonate and calcium carbonate groups. The differences in the corrected serum calcium level or the calcium × phosphate products between the 2 groups were not statistically significant. However, the mean change in the corrected serum calcium level from baseline to the last outpatient visit was significantly lower in the lanthanum carbonate group than in the calcium carbonate group. The incidence of hypercalcemia in the lanthanum carbonate group was also significantly lower than in the calcium carbonate group. Conclusion: Both compounds show similar efficacy on the serum phosphate level in patients undergoing hemodialysis when the dose is managed in a dose-variable and double-blind manner. However, lanthanum carbonate is superior in terms of lowering the incidence of hypercalcemia.Correspondence to:
T. Shigematsu, MD, PhD; Nephrology and Blood Purification Medicine, Wakayama Medical University, 881-1, Kimiidera Wakayama-City, Wakayama Prefecture, 641-8509, Japan
Email: taki@wakayama-med.ac.jp

Abstract

B.C.P. Koch¹, J.E. Nagtegaal¹, E.C. Hagen², W.Th. van Dorp³, J.B.S. Boringa⁴, G.A. Kerkhof⁵ and P.M. Ter Wee⁶

¹Department of Clinical Pharmacy, ²Department of Internal Medicine, Amersfoort, ³Department of Internal Medicine, Haarlem, ⁴Department of Neurology, Amersfoort, ⁵Department of Psychology, University of Amsterdam, ⁶Department of Nephrology, University Medical Centre, Amsterdam, The Netherlands
Background: Sleep disturbances have a major influence on quality of life. A commonly used measure of sleep disturbances is sleep efficiency. The purpose of this study was to investigate the prevalence of decreased subjective sleep efficiency in hemodialysis patients. An additional goal was to identify clinical, dialysis or laboratory parameters that are independently associated with decreased sleep efficiency. Methods: Adult stable hemodialysis patients (n = 112) filled out a sleep questionnaire during a three day investigation period. In addition, healthy control subjects (n = 44) filled out the same questionnaire. From this questionnaire sleep efficiency (ratio of total sleep time to time spent in bed) was derived as a measure for sleep disturbances in this population. Laboratory, demographic and dialysis data were collected during the investigation period. For statistical analysis linear regression models were used. Results: Median subjective sleep efficiency in hemodialysis patients was 80%, which was significantly less compared to the median subjective sleep efficiency of control subjects of 88% (p £ 0.05). Approximately 40% of the patients used sleep medication. However, less than 20% of them indicated improved sleep behavior when using these drugs. Elevated levels of phosphate and urea correlated independently with impaired sleep efficiency. Hemoglobin levels between 10 and 12 g/dl were associated with better sleep efficiency. Conclusion: In conclusion, decreased sleep efficiency was frequently reported in hemodialysis patients and can be associated with biochemical parameters. Hemoglobin, phosphate and urea levels can affect subjective sleep efficiency.Correspondence to:
B.C.P. Koch, PharmD; Department of Clinical Pharmacy, Meander MC, Postal box 1520,
3800 BM Amersfoort, The Netherlands
Email: bcp.koch@meandermc.nl

Abstract

R. Liebl¹ and B.K. Krämer²

¹KfH-Nierenzentrum, Regensburg and ²Marienhospital Herne, Ruhr-Universität Bochum, Germany
Membranous nephropathy is the most frequent cause of nephrotic syndrome in adults and the reason for renal failure and dialysis in 5%. After renal transplantation, recurrent membranous nephropathy occurs in 10 – 30%. There is no established therapy for recurrent membranous nephropathy. This case report describes a probably spontaneous clinical remission of a recurrent membranous nephropathy after renal transplantation. The message of the case report is that there could be spontaneous remissions of membranous nephropathy also after renal transplantation and that remissions seen after various therapeutic maneuvers as described in case reports and case series might either be the consequence of that therapy or represent spontaneous remission.Correspondence to:
Dr. R. Liebl; KfH-Nierenzentrum and internistisch-nephrologische Gemeinschaftspraxis, Günzstraße 4, 93059 Regensburg, Germany
Email: robert.liebl@kfh-dialyse.de

Abstract

C. Muller, F. Alenabi, F. Chantrel, S. Muller, C. Trivin and B. Faller

Department of Nephrology, Hôpital Civil de Colmar, Colmar, France
Membranous nephropathy rarely occurs as a familial disease. We report two siblings (brother and sister) who presented with nephrotic syndrome and many vascular complications. HLA identities and potential toxic exposure may be concurring in these cases.Correspondence to:
C. Muller, MD; Department of Nephrology, Hôpital civil de Colmar, Avenue Rome, 68000 Colmar,
France
Email: clotilde-muller@hotmail.fr

Abstract

N. Yildiz¹, F. Ardic¹, Ö. Ercidogan¹ and S. Coban²

¹Department of Physical Medicine and Rehabilitation and ²Department of Pathology, Faculty of Medicine, Pamukkale University, Denizli, Turkey
Articular involvement such as osteodystrophy, osteonecrosis, dialysis-related amyloidosis, septic arthritis, malignancy and various crystal-induced arthropathies among patients with chronic renal failure is common. Cases of pseudogout (calcium pyrophosphate deposition disease) in patients with renal failure have been seen rarely in the literature. In these cases, acute pseudogout arthritis in only one joint such as an elbow, a wrist or an ankle in uremic patients has been reported. In our case, unlike the previously reported cases, pseudogout is found for the first time as the cause of arthritis which is concomitant in both knee and wrist joints in an uremic patient.Correspondence to:
Prof. F. Ardic, MD; Department of Physical, Medicine and Rehabilitation, Faculty of Medicine, Pamukkale University, 6078 sok. No: 15/5 Kinikli, 20070, Denizli, Turkey
Email: fardic@pau.edu.tr

Abstract

M. Thaha¹, Pranawa¹, M. Yogiantoro¹, M. Tanimoto² and Y. Tomino²

¹Division of Nephrology-Hypertension, Department of Internal Medicine, Airlangga University School of Medicine, Surabaya, Indonesia, and ²Division of Nephrology, Department of Internal Medicine, Juntendo University School of Medicine, Tokyo, Japan
Malaria is an infectious disease caused by plasmodium, which lives and breeds in human blood cells, and is transmitted through the bites of Anopheles mosquitoes. Renal impairment, often caused by malaria, is acute renal failure (ARF) due to acute tubular necrosis (ATN). Dengue virus is transmitted from human to human through Aedes aegypti mosquito bites. Dengue hemorrhagic fever (DHF), the most severe stage of infection, is characterized by bleeding and shock tendencies (dengue shock syndrome, DSS). ARF is a less common complication in patients with DHF, with an incidence of less than 10%. Mixed infections of two infectious agents may cause overlapping symptoms and have been reported in Africa and India. We report here a patient with ARF due to mixed infection of severe malaria and DSS. The patient presented with fever and had a history of repeated malaria infection. Physical examination revealed stable vital signs and hepatosplenomegaly. Laboratory data showed hemoconcentration, thrombocytopenia and increased serum aminotransferase. Chest X-ray showed pleural effusion. A malarial antigen and thick smear examination showed the trophozoite stage of P. falciparum. On Day 3, blood pressure dropped to 80/60 mmHg, pulse was 120 beats/minute, weak, and body temperature 36.8 ºC, with icterus. Other tests revealed an increase of serum urea nitrogen and creatinine levels, and serologically anti-dengue IgG antibody (+) and anti-dengue IgM antibody (–). Based on these findings, we diagnosed the patient as having both malaria and DDS. We treated the patient with the parenteral anti-malarial agent, artemisinin. Supportive treatment and treatment of complications were also performed simultaneously for DSS. The patient experienced an oliguria episode but responded well to a diuretic. The patient was discharged after clinical and laboratory examinations showed positive progress.Correspondence to:
Prof. Y. Tomino, MD; Division of Nephrology, Department of Internal Medicine, Juntendo University School of Medicine, 2-1-1 Hongo, Bunkyo-ku, Tokyo, 113-8421, Japan
Email: yasu@med.juntendo.ac.jp

Abstract

M. Woznowski¹, I. Quack¹, J. Stegbauer¹, L.C. Rump¹, G. Schieren¹ and N. Büchner²

¹Department of Nephrology, Heinrich-Heine-University, Duesseldorf and ²Department of Nephrology, Marienhospital Herne, Ruhr-University Bochum, Germany
An appropriate phosphate homeostasis is absolutely required for correct bone mineralization and remodeling, for diverse signaling pathways as well as cell membrane formation. Its disequilibrium results in serious complications like hypophosphatemia and excessively reduced fractional tubule phosphate reabsorption (TRP). A rare cause of such a disturbed phosphate balance is tumor-induced osteomalacia (TIO) – a phosphate wasting disorder sometimes associated with certain mesenchymal tumors. These primitive tumors secrete so-called phosphatonins – recently identified factors involved in the regulation of phosphate homeostasis such as the secreted frizzled related protein 4 (sFRP-4), the fibroblast growth factors 7 and 23 (FGF-7/-23), or the matrix extracellular phosphoglycoprotein (MEPE). Progressive muscular weakness and spontaneous bone fractures caused by inadequate osteoid mineralization are the characteristic clinical symptoms, which completely resolve after tumor resection. Here we report a new case of TIO caused by tumor secreted FGF-23 and review the literature to facilitate the correct diagnosis of this rare disorder.Correspondence to:
M. Woznowski, MD; Department of Nephrology, Heinrich-Heine-University, Moorenstraße 5, 40225 Duesseldorf, Germany
Email: Magdalena.Woznowski@med.uni-duesseldorf.de

Abstract

M. Koch and M. Kohnle

Center of Nephrology, Mettmann, Germany
We describe the case of a young man with pseudohypoparathyroidism Type 1b – a rare genetic disorder characterized by end-organ resistance to parathormone (PTH) – and vitamin D intoxication sequelae due to inappropriate and poorly monitored calcitriol treatment in his adolescence, who could no longer be successfully treated by standard vitamin D treatment alone. Off-label administration of cinacalcet HCl, a calcimimetic approved for the treatment of secondary hyperparathyroidism, together with the vitamin D analog dihydrotachysterol, however, proved successful in controlling parathormone (PAH), bone-specific alkaline phosphatase (BAP), serum calcium, and phosphate levels.Correspondence to:
M. Koch, MD; Gartenstraße 8, 40822 Mettmann,
Germany
Email: Koch@dialyse-mettmann.de

Abstract

M. Tokunaga, M. Tamura, N. Kabashima, R. Serino, T. Shibata, M. Matsumoto, T. Miyamoto, M. Miyazaki, Y. Furuno, J. Nakamata, M. Takeuchi, H. Abe, M. Okazaki and Y. Otsuji

Abstract

M. Schina, P. Karsaliakos, T. Apostolou and G. Mousoulis

Abstract

B. Yildirim, G.S. Dumlu, S. Unal, H. Saritas, M. Yasar and E. Isikta

Abstract

K.M. Kim, J.M. Cho, H.J. Park, H.W. Kim, W.S. Yang, S.B. Kim, S.-K. Park, S.K. Lee, J.S. Park and J.W. Chang

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Volume 70, No. 5/2008(November)