Volume 68, No. 1/2007(July)
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 Clinical Nephrology
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Review
Low-grade inflammation in chronic kidney disease patients before the start of renal replacement therapy: sources and consequences
Abstract
M.I. Yilmaz, J.J. Carrero, J. Axelsson, B. Lindholm and P. Stenvinkel
Divisions of Renal Medicine and Baxter Novum, Department of Clinical Science, Intervention and Technology, Karolinska Institutet, Karolinska University Hospital at Huddinge, Stockholm, Sweden
Low-grade inflammation is a common feature of chronic kidney disease (CKD) already before the start of renal replacement therapy, and evidence suggests that persistent inflammation may also be per se a risk factor for progression of CKD and vascular disease. Many factors, including retention of pro-inflammatory cytokines, advanced glycation end products, reactive oxygen species, autonomic dysfunctions and volume overload may contribute to inflammation when renal function declines. The aim of the present review is to summarize the causes and consequences of a chronic inflammatory state in the CKD population before start of renal replacement therapy, with special emphasis in polymorphnuclear leukocyte priming, which may be a key mediator in the induction of a vicious circle of oxidative stress and inflammation in CKD. A more thorough characterization of uremic retention solutes with regard to their specific pro- and anti-inflammatory properties is needed.Correspondence to:
P. Stenvinkel, MD, PhD
Department of Renal Medicine, K56
Karolinska University Hospital at Huddinge
141 86 Stockholm, Sweden
Email: peter.stenvinkel@ki.se
Originals
Cinacalcet HCl (Sensipar/ Mimpara) is an effective chronic therapy for hemodialysis patients with secondary hyperparathyroidism
Abstract
J.R. Sterrett, J. Strom, H.-K. Stummvoll†, U. Bahner, A. Disney, S.D. Soroka, C. Corpier, J.A. Arruda, L.E. Schwanauer, P.S. Klassen, K.A. Olson and G.A. Block
1St. Joseph Regional Medical Center, Paterson, NJ, 2Caritas St. Elizabeth’s Medical Center and Tufts University School of Medicine, Boston, MA, USA, 33. Interne Abteilung – Nephrologie, Krankenhaus der Elisabethinen Linz, Austria, 4KfH Kuratorium für Dialyse und Nierentransplantation e.V., University of Würzburg, Germany, 5Queen Elizabeth Hospital, Adelaide, SA, Australia, 6Center for Clinical Research, Dalhousie University, Halifax, Nova Scotia, Canada, 7Dallas Nephrology Associates, Dallas, TX, 8Department of Medicine, Section of Nephrology, University of Illinois, Chicago, IL, 9Amgen Inc., Thousand Oaks, CA and 10Denver Nephrologists, Denver, CO, USA
Aims: This 1-year double-blind, placebo-controlled, multicenter study evaluated the long-term safety and efficacy of cinacalcet for the treatment of secondary hyperparathyroidism in patients receiving hemodialysis. Method: Patients were randomly assigned in a 1 : 1 ratio to cinacalcet or control treatment groups. The initial dose of cinacalcet (or matching placebo) was 30 mg. Doses were titrated every 3 or 4 weeks based on the intact parathyroid hormone (iPTH) response and safety profile. Sequential doses included 30, 60, 90, 120 and 180 mg/d. Phosphate binders and vitamin D sterols were adjusted per protocol as needed to control levels of calcium and phosphorus. Efficacy and safety were compared between treatment groups among patients who completed the study (52 total weeks of treatment). Reasons for withdrawal are presented for patients who did not complete the study. Results: A total of 210 patients completed 52 weeks of double-blinded treatment with cinacalcet (n = 99) or placebo (n = 111). Over the last 6 months of the study, a greater proportion of patients in the cinacalcet group than the control group achieved an iPTH level <= 250 pg/ml (61.6 vs. 9.9%, p < 0.001) or a >= 30% decrease in iPTH from baseline (81.8 vs. 21.6%, p < 0.001). Mean iPTH levels decreased by –47.8% in the cinacalcet group and increased by +12.9% in the control group. Mean percentage changes in other laboratory values in the cinacalcet and control groups included the following: serum calcium –6.5 vs. +0.9% (p < 0.001), serum phosphorus –3.6 vs. –1.1% (p = 0.465), and Ca × P –9.9 vs. –0.3% (p = 0.006). The most commonly reported adverse events related to study drug by the investigators included nausea (13% cinacalcet, 5% control), investigator-reported hypocalcemia (11% cinacalcet, 1% control), vomiting (9% cinacalcet, 2% control), dyspepsia (5% cinacalcet, 4% control), and diarrhea (5% cinacalcet, 2% control). Conclusions: Treatment with cinacalcet is a safe and effective therapy for long-term control of secondary hyperparathyroidism. 1-year therapy with cinacalcet was associated with sustained, clinically significant reductions in calcium, Ca × P and iPTH which allowed a greater percentage of patients to achieve NKF-KDOQI target goals for PTH and Ca × P.Correspondence to:
J.R. Sterrett, MD Chairman Department of Medicine Medical Surgical Specialists 6101 Pine Ridge Road Naples, FL 34119, USA
Email: reidsterrett@yahoo.com
Originals
The prognostic value of the C-reactive protein levels in HD patients with death risk from infection
Abstract
M. Koch, B. Haastert and R. Trapp
1Center of Nephrology, Mettmann, 2Institute of Biometrics and Epidemiology, German Diabetes Center, Leibniz Center at Heinrich Heine University, Düsseldorf, Germany
Aims: Infection is considered the second leading cause of death in dialysis patients with end-stage renal disease (ESRD). However, infection prevalence as primary cause of death still seems to be underreported in the literature. We investigated the role of C-reactive protein (CRP) levels shortly before death as predictor of dying from an infection as primary cause of death in this patient group. Method: Between January 1997 through March 2006, we defined the primary causes of death in 231 of the 481 incident patients in our single-center study, who died during this time and assessed the overall prevalence of infection at different predefined CRP cutpoints (between 2 and 300 mg/l). By means of an adjusted multiple logistic regression model, we calculated the odds ratio of (log) CRP for death in 346 survivors and non-survivors with available CRP levels within 5 days of death. In the 96 non-survivors (i.e. cases) of this group, the association of (log) CRP and causes of death was determined by the multiple linear regression model. Results: Infection as a primary cause of death was initially diagnosed in 42% of the 231 non-survivors by standard parameters and clinically. However, the rate of patients possibly dying from this disease increased accordingly when also including cases without any clinical infection signs but with CRP values higher than a given cutpoint (between 2 and 300 mg/l), e.g. when including all cases with CRP cutpoints higher than 100 mg/l, overall prevalence of infection as cause of death increases to 57% (95% CI = 51 – 64%). Infection was significantly associated with higher CRP levels compared with cardiac death (p < 0.001), with an odds ratio of log CRP for death of 5.4 (95% CI = 3.8 – 7.7). Conclusions: Prevalence of infection as primary cause of death in ESRD patients may be even higher than currently stated in the literature. Therefore, to reduce mortality, infections should be further avoided and controlled in the future.Correspondence to:
M. Koch, MD Gartenstraße 8 40822 Mettmann, Germany
Email: Koch@dialyse-mettmann.de
Originals
The first human cell line-derived erythropoietin, epoetin-δ (Dynepo®), in the management of anemia in patients with chronic kidney disease
Abstract
K.J. Martin
Division of Nephrology, Saint Louis University, St. Louis, MO, USA
Aims: To evaluate the efficacy and safety of the first human cell line-derived erythropoietin, epoetin-δ, in the management of anemia in patients with chronic kidney disease. Methods: This was a multicenter, randomized, double-blind, parallel-group, active-control, Phase III study. Patients aged >= 18 years with chronic renal disease requiring hemodialysis, with hemoglobin (Hb) levels in the range 9.6 – 12.4 g/dl, and who had been treated with recombinant erythropoietin for >= 90 days before study entry were eligible. In the initial double-blind comparative study phase, patients were randomized in a 3 : 1 ratio to 24-week treatment with either intravenous (i.v.) epoetin-d (ED) or epoetin-a (EA). Patients then entered a 28-week open-label phase, receiving i.v. ED at a dose equal to that of i.v. ED or EA which they received at the end of the blinded phase. Results: In total, 752 patients were randomized, of whom 555 patients subsequently received ED and 191 patients EA, with 583 patients (77.5%) completing the double-blind phase and entering the open-label phase. There was no significant difference between groups for the primary endpoint: the average Hb level from Weeks 12 – 24 of the study. The adjusted mean average Hb level for the modified intent-to-treat (mITT) population was 11.57 g/dl in the ED group (n = 491, mean dose 63.5 IU/kg) and 11.56 g/dl in the EA group (n = 175, mean dose 62.8 IU/kg). Efficacy was maintained on long-term use. Data for Weeks 12 – 52 show that ED maintained patients’ Hb levels in the target range (10 – 12 g/dl) with a mean Hb level of 11.31 g/dl at a mean ED dose of 63.7 IU/kg. ED therapy was well tolerated, with a similar overall incidence of adverse events (AEs) (94.4%) to the EA group (92.1%) in the double-blind phase (most common events: hypotension, upper respiratory tract infection, muscle cramps, headache). AEs occurring during the open-label phase were generally similar in type and frequency to those reported during the double-blind phase. Conclusions: The human cell line-derived erythropoietin, epoetin-d, provides an effective, well tolerated new option for the management of anemia in patients with chronic kidney disease.Correspondence to:
K.J. Martin, MB, B.Ch, FACP
Division of Nephrology
Saint Louis University
3634 Vista Avenue
St. Louis, MO 63110, USA
Email: martinkj@slu.edu
Case Reports
Recovery of acute renal failure following bilateral renal artery angioplasty and stenting
Abstract
E. Kuznetsov, B. Schifferdecker, B.L. Jaber, P. Soukas and O. Liangos
1Department of Medicine, Division of Nephrology, 2Division of Vascular Medicine, Caritas St. Elizabeth’s Medical Center, Boston, MA, USA
Atherosclerotic renovascular disease commonly coexists with chronic kidney disease, and its optimal management remains unsettled. In this case report, we describe a 75-year-old woman with chronic kidney disease and critical atherosclerotic bilateral renal artery stenosis, who presented with a hypertensive emergency and developed acute renal failure following antihypertensive treatment. Bilateral percutaneous transluminal renal angioplasties (PTRA) with stent placement were performed and resulted in immediate recovery of renal function. The existing literature on this impressive response to PTRA is reviewed and discussed.Correspondence to:
O. Liangos, MD Caritas St. Elizabeth’s Medical Center CBR 423, Department of Medicine 736 Cambridge Street Boston, MA 02135, USA
Email: orfeas.liangos@caritaschristi.org
Case Reports
Postpartum hemolytic uremic syndrome in a patient with preexisting hypertension and resolving preeclampsia
Abstract
J.S. Karam, P. Pitiranggon, H. Wheat, B. Stefanick and R.C. Venuto
1Division of Nephrology, 2Department of Pathology, State University of New York at Buffalo, Buffalo, NY, USA
Postpartum hemolytic uremic syndrome (PHUS) is an uncommon and potentially devastating complication of pregnancy. We report a case of PHUS in a patient with chronic hypertension and preceding preeclampsia. Since early and appropriate therapy results in remission in most patients with PHUS, the sometimes subtle differences between this syndrome and preeclampsia are reviewed.Correspondence to:
R.C. Venuto, MD
Nephrology Department
Erie County Medical Center
462 Grider Street
Buffalo, NY 14215, USA
Email: acase@ams.ecmc.edu
Case Reports
Severe emphysematous pyelonephritis in a renal allograft: successful treatment with percutaneous drainage and antibiotics
Abstract
Y.-W. Chuang, C.-H. Chen, C.-H. Cheng, S.-W. Hung, T.M. Yu, M.J. Wu and K.-H. Shu
1Department of Medicine, Division of Nephrology,
2Department of Radiology, Taichung Veterans General Hospital and
3School of Medicine, Chung-Shan Medical University, Taichung, Taiwan
Emphysematous pyelonephritis is a rare, severe gas-forming infection of the kidney. Herein we report a case of a 51-year-old man who had received a cadaveric renal transplant 12 years ago. Post-transplant diabetes mellitus occurred 8 years later. He experienced urinary tract infection with graft pain one week before admission and presented with septic shock at the emergency room. Plain X-ray of the abdomen showed retroperitoneal air. A computed tomography scan of the abdomen showed retroperitoneal and extraperitoneal air being released from the graft kidney. These findings were compatible with extensive emphysematous pyelonephritis. The patient underwent percutaneous drainage. Blood culture and urine culture yielded Escherichia coli. After repeated percutaneous drainage and strong antibiotics for a prolonged period, the patient finally recovered.Correspondence to:
K.-H. Shu, MD
Division of Nephrology, Department of Medicine
Taichung Veterans General Hospital,
No. 160, Section 3, Chung-Kang Road
Taichung, 407, Taiwan
Email: khshu@vghtc.gov.tw
Case Reports
Rapid onset intratubular calcification following renal transplantation requiring urgent parathyroidectomy
Abstract
A. Sewpaul, J.A. Sayer, M.A.S. Mohamed, A. Ahmed, M. Shaw, V.R. Prabhu, K. Wood, N.A. Jones, D. Talbot and N.S. Kanagasundaram
1Renal Transplant Unit Freeman Hospital, 2Institute of Human Genetics, Newcastle University, International Center for Life, 3Department of Nephrology, Freeman Hospital, 4Department of Cellular Pathology, Royal Victoria Infirmary, 5Departments of Vascular and Endocrine Surgery, Freeman Hospital, Newcastle upon Tyne, United Kingdom
Background: Secondary hyperparathyroidism is a common complication of end-stage renal disease often requiring parathyroidectomy. Renal transplant with the restoration of normal renal function often allows resolution of hyperparathyroidism, avoiding the need for parathyroid surgery. However, a proportion of patients with hyperparathyroidism become overtly hypercalcemic after renal transplantation which poses management dilemmas between medical and surgical treatment. Case: We present the case of a 48-year-old man with end-stage renal failure known to have secondary hyperparathyroidism who received a living related renal transplant. Postoperatively he developed prompt hypercalcemia, polyuria, polydipsia and rapid onset intratubular calcification, leading to acute tubular necrosis diagnosed on renal biopsy on Day 7 post transplantation. He underwent surgical parathyroidectomy with resolution of his hypercalcemia and improved renal transplant function. Discussion: This case emphasizes the need for good management of secondary hyperparathyroidism together with close surveillance of PTH in patients awaiting renal transplantation. With good renal transplant function hyperparathyroidism usually resolves. Posttransplant surgical parathyroidectomy should be reserved for severe progressive end organ damage.Correspondence to:
Dr. J.A. Sayer
Institute of Human Genetics, Newcastle University
International Center for Life
Central Parkway
Newcastle upon Tyne, NE1 3BZ, United Kingdom
Email: j.a.sayer@ncl.ac.uk
Case Reports
Peritonitis associated with Pasteurella multocida in peritoneal dialysis patients – case report and review of the literature
Abstract
S.J. Antony and K.A. Oglesby
1Center for Infectious Diseases and Travel Medicine, 2Continuing Medical Education, Texas Tech University Health Sciences Center, El Paso, TX, USA
Pasteurella multocida is a zoonotic pathogen found in the oral cavities of domestic dogs and cats and other wild and domestic animals. 14 cases of peritoneal dialysis-associated Pasteurella multocida peritonitis linked to animal contact have been reported in the literature to date. In each case, the source of infection was believed to be a domestic cat or cats. One case of spontaneous bacterial peritonitis has been reported in a cirrhotic patient and was not linked to animal contact. Poor hygiene in relation to pets was considered the source of infection. We describe the first case of Pasteurella multocida peritonitis in a patient undergoing continuous ambulatory peritoneal dialysis (CAPD) believed to be caused by contact with dogs and discuss the relevant literature.Correspondence to:
S.J. Antony, MD, FACP
Center for Infectious Diseases and Travel Medicine
1205 N Oregon
El Paso, TX 79902, USA
Email: santony@elp.rr.com
Letters to the Editor
Pseudohyperkalemia identified in a myelofibrosis patient exhibiting giant platelets and nucleated red blood cells
Abstract
C. Duplessis, D. Rakowski, E. Yeung and M. Hopkins
Naval Hospital, Portsmouth, VA, USA
Correspondence to:
C. Duplessis, MD
4613 Burkett Court
Chesapeake, VA 23321, USA
Email: mduplessis4@cox.net
Letters to the Editor
Renal angiomyolipoma with a minimal fatty component mimicking renal cell carcinoma
Abstract
K.P. Kang, S. Lee, W. Kim, I.Y. Yun, S.Y. Park, S.Y. Lee, H.J. Kim and S.K. Park
1Department of Internal Medicine and Renal Regeneration Laboratory, 2Radiology, 3Urology, Chonbuk National University Medical School and Institute for Medical Sciences, Jeonju, Republic of Korea
Correspondence to:
S.K. Park, MD
Department of Internal Medicine and
Renal Regeneration Laboratory,
Chonbuk National University Medical School,
634-18, Keumam Dong, Jeonju, 561-712,
Republic of Korea
Email: parksk@chonbuk.ac.kr
Letters to the Editor
A case of hydronephrosis caused by a precaval right lower polar artery
Abstract
I.Y. Yun, S. Lee, K.P. Kang, W. Kim, S.Y. Lee, Y.G. Kim and S.K. Park
1Department of Internal Medicine, 2Diagnostic Radiology, and
3Department of Urology, Renal Regeneration Laboratory, Research Institute of Clinical Medicine, Chonbuk National University Medical School, Jeonju, Republic of Korea
Correspondence to:
S.K. Park, MD
Department of Internal Medicine
Renal Regeneration Laboratory
Chonbuk National University Medical School
634-18, Keum-Am Dong
Jeonju, 561-712, Republic of Korea
Email: kidney@chonbuk.ac.kr
Letters to the Editor
12 months cinacalcet therapy in hemodialysis patients with secondary hyperparathyroidism: effect on bone markers
Abstract
G. Jean, C. Chazot and B. Charra
Centre de Rein Artificiel, Tassin la demi-lune, France
Correspondence to:
Dr. G. Jean
Centre de Rein Artificiel
42 avenue du 8 mai 1945
69160 Tassin la demi-lune, France
Email: guillaume-jean-crat@wanadoo.fr
