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Abstract

B. Ling, M. Walczyk, A. Agarwal, W. Carroll, W. Liu and R. Brenner

¹Mountain Kidney Associates, Asheville, NC, ²Northwest Renal Clinic Inc., Portland, OR, ³Ohio State University Medical Center, Columbus, OH, and ⁴Amgen Inc., Thousand Oaks, CA, USA
Background: Darbepoetin alfa is an erythropoiesis-stimulating glycoprotein that functions by the same mechanism as recombinant human erythropoietin (rHuEPO), but has a three-fold longer serum half-life. Reduction in the frequency of darbepoetin alfa administration would be beneficial to patients with renal disease and their healthcare providers. This study evaluated the effect of extending the darbepoetin alfa dosing interval to once monthly in patients with chronic kidney disease (CKD) not receiving dialysis. Methods: This study was a multicenter, open-label study of 97 patients with CKD not on dialysis. Patients receiving stable subcutaneous doses of darbepoetin alfa once every two weeks were converted to darbepoetin alfa once monthly for 29 weeks. The proportion of patients who successfully maintained hemoglobin concentrations between 10.0 and 12.0 g/dl and the mean darbepoetin alfa dose were evaluated. Safety measurements (e.g. adverse events, laboratory parameters, blood pressure) and seroreactivity were assessed. Results: Hemoglobin concentration was maintained within the target range in 79% (95% confidence interval (CI) = 71% to 87%) of all patients receiving darbepoetin alfa and in 85% (95% CI = 78% – 93%) of patients who completed the study period. The mean ± standard deviation monthly darbepoetin alfa dose was similar between baseline (88.7 ± 49.9 mg) and the evaluation period (86.6 ± 78.8 mg). The safety profile for monthly darbepoetin alfa administration was comparable with that previously observed with more-frequent administration. Conclusion: Patients with CKD who are clinically stable on darbepoetin alfa administered once every two weeks can be safely and effectively converted to darbepoetin alfa administered once monthly.Correspondence to:
B. Ling, MD
Mountain Kidney Associates
10 McDowell Street
Asheville, NC 28801, USA
Email: loganling@aol.com

Abstract

R.D. Swartz, R.T. Bustami, J.M. Daley, B.W. Gillespie and F.K. Port

¹Department of Internal Medicine, Division of Nephrology, University of Michigan Health System, ²University Renal Research and Education Association (URREA), and ³Department of Biostatistics, University of Michigan School of Public Health, Ann Arbor, MI,
Background: Mortality in severe acute renal failure (ARF) requiring renal replacement therapy (RRT) approximates 50% and varies with clinical severity. Continuous RRT (CRRT) has theoretical advantages over intermittent hemodialysis (IHD) for critical patients, but a survival advantage with CRRT is yet to be clearly demonstrated. To date, no prospective controlled trial has sufficiently answered this question, and the present prospective outcome study attempts to compare survival with CRRT versus that with IHD. Methods: Multivariable Cox-proportional hazards regression was used to analyze the impact of RRT modality choice (CRRT vs. IHD) on in-hospital and 100-day mortality among ARF patients receiving RRT during 2000 and 2001 at University of Michigan, using an “intent-to-treat” analysis adjusted for multiple comorbidity and severity factors. Results: Overall in-hospital mortality before adjustment was 52%. Triage to CRRT (vs IHD) was associated with higher severity and unadjusted relative rate (RR) of in-hospital death (RR = 1.62, p = 0.001, n = 383). Adjustment for comorbidity and severity of illness reduced the RR of death for patients triaged to CRRT and suggested a possible survival advantage (RR = 0.81, p = 0.32). Analysis restricted to patients in intensive care for more than five days who received at least 48 hours of total RRT, showed the RR of in-hospital mortality with CRRT to be nearly 45% lower than IHD (RR = 0.56, n = 222), a difference in RR that indicates a strong trend for in-hospital mortality with borderline statistical significance (p = 0.069). Analysis of 100-day mortality also suggested a potential survival advantage for CRRT in all cohorts, particularly among patients in intensive care for more than five days who received at least 48 h of RRT (RR = 0.60, p = 0.062, n = 222). Conclusion: Applying the present methodology to outcomes at a single tertiary medical center, CRRT may appear to afford a survival advantage for patients with severe ARF treated in the ICU. Unless and until a prospective controlled trial is realized, the present data suggest potential survival advantages of CRRT and support broader application of CRRT among such critically ill patients.Correspondence to:
R.D. Swartz, MD
Division of Nephrology
3914 Taubman Ctr, Box 0364
University of Michigan Health System
Ann Arbor, MI 48109-0364, USA
Email: rswartz@med.umich.edu

Abstract

L. Zhang, M. Wang and H. Wang

Division of Nephrology, Peking University First Hospital, Beijing, China
Background: Acute renal failure in chronic kidney disease (A/C) constitutes an important part of acute renal failure (ARF), but until now there has been no research focusing on this entity. Patients and methods: Clinical data were collected from all patients diagnosed as A/C by clinical materials and renal biopsy over a 12-year period (January 1990 – December 2001) in the renal department of a teaching hospital, and the incidence, etiology, pathological and clinical features of A/C, and factors predicting prognosis were studied. Results: Altogether, 104 patients of A/C were identified, which accounted for 35.5% of biopsied acute renal failure cases during the same period. Drug-induced acute renal interstitial/tubular-interstitial disease, prerenal ARF and flare-up of lupus nephritis were the most common causes of ARF in A/C patients. More than one third of A/C were associated with drugs, which occurred more commonly in older patients. After an average hospitalization of 28.5 days, about 39 patients required dialysis, 23 patients became dialysis-independent. The mortality was 1.9%. Furthermore, serum creatinine (Scr) returned to normal level (< 133 mmol/l) in 46.2% of all patients; Scr decreased by 15%, yet not normal in 26.0%. Multivariate logistic regression analysis indicated that hypertension, requirement of dialysis therapy and high Scr level were independent predictors of poor renal outcome. Conclusion: A/C constitutes an important part of ARF, and drug-induced ARF is prominent in China. Because early diagnosis and correct treatment may obviously affect prognosis, enough attention should be paid to this entity.Correspondence to:
H. Wang, MD

Division of Nephrology

Peking University First Hospital

No. 8. Xishiku Street

Beijing, China 100 034
Email: why@bjmu.edu.cn

Abstract

J.-M. Chang, S.-P. Lin, H.T. Kuo, J.-C. Tsai, Y. Tomino, Y.-H. Lai and H.-C. Chen

¹Department of Nephrology, Kaohsiung Medical University,
²Department of Internal Medicine, Hsiao-Kang Municipal Hospital, Taiwan, and ³Division of Nephrology, Juntendo University, Tokyo, Japan
Aims: Recent progress in PTH assay has revealed that the intact PTH assay kit in current use does not differentiate between the truncated 7-84 PTH molecule and the 1-84 PTH molecule. In our series, we examined the effectiveness of a new PTH assay as a noninvasive method of evaluating severity of uremic hyperparathyroidism. Methods and materials: Two hundred and seventy hemodialysis (HD) patients recruited from three HD centers were included and divided into subgroups according to the conventional iPTH assay results. Pre-dialysis blood samples were collected and subjected to two different PTH assays: “intact” PTH assay (iPTH) and “whole” PTH (wPTH) assay. Two biochemical markers of bone remodeling were also examined. Results: In all cases, PTH levels determined by the wPTH assay were in the average 32.3% lower than those determined by the iPTH assay. The difference of the results of the two PTH assay methods, which indicated the portion of 7-84 PTH fragments of the total PTH molecules measured with the iPTH assay, was gradually increased while the severity of uremic hyperparathyroidism increased. Biochemical markers of bone formation/resorption showed a similar change. Conclusion: The portion of the 7-84 PTH fragments and markers of increased bone turnover increased in proportion to the severity of uremic hyperparathyroidism. This finding disproves the hypothetical role of 7-84 PTH fragments alone as the noninvasive marker of low-turnover bone disease in HD patients.Correspondence to:
H.-C. Chen, MD, PhD
Division of Nephrology
Kaohsiung Medical University
100 Shih-Chuan 1st Rd
Kaohsiung 807, Taiwan
Email: chenhc@kmu.edu.tw

Abstract

G.J. Vlachojannis, K. Scholz-Pedretti, W. Fierlbeck, H. Geiger, J. Pfeilschifter and M. Kaszkin

¹Pharmazentrum Frankfurt, and ²Department of Nephrology, University Hospital, Frankfurt/Main, Germany
Background: Group IIA secreted phospholipase A2 (sPLA2-IIA) has been implicated in various inflammatory processes including the kidney. Previously it has been shown that potent proinflammatory cytokines such as interleukin 1b (IL-1b) increase sPLA2-IIA expression and secretion in rat mesangial cells. Aim: The present study examines the effects of glucose on sPLA2-IIA regulation in interleukin-1b (IL-1b) treated mesangial cell cultures and in diabetic kidneys of Sprague-Dawley rats. Materials and Methods: Rat mesangial cells were grown either in low glucose (5,55 mM D-Glucose) or high glucose (25 mM) conditions followed by assessment of sPLA2-IIA transcription, expression and secretion after 24 h. The model of streptozotocin induced diabetes mellitus in Sprague-Dawley rats was used for the in vivo experiments. Diabetic kidneys where examined for sPLA2-IIA-mRNA and -protein expression as well as IL-1b-levels at 2, 4 and 6 weeks after induction of diabetes mellitus. Results: Increased concentration of glucose had a weak, but significant stimulatory effect on sPLA2-IIA expression, which was markedly up-regulated (2 – 3-fold) in IL-1b treated mesangial cells compared to the levels obtained in low glucose medium. Concerning the underlying mechanism, we found that high concentration of glucose increased the activity of the rat sPLA2-IIA-promoter, whereas mRNA stability was not affected. Furthermore, the in vivo experiments revealed a marked up-regulation of sPLA2-IIA mRNA and protein in the diabetic rat kidneys 2 – 4 weeks after induction. Since the strong up-regulation of sPLA2-IIA in vitro under high glucose conditions occurred mainly in presence of cytokine, we measured the levels of IL-1b in diabetic kidneys by ELISA. We detected rat IL-1b only in diabetic, but not in control rat kidneys. Conclusions: The changes of sPLA2-IIA expression under increased glucose concentrations as well as in diabetic rat kidneys suggest a function of this enzyme as an acute phase protein providing lipid autacoids that may contribute to early changes in the course of diabetic nephropathy.Correspondence to:
PD Dr. med. M. Kaszkin
Institute for General Pharmacology and Toxicology
Pharmazentrum Frankfurt
University Clinic
Theodor-Stern-Kai 7
60590 Frankfurt/Main, Germany
Email: marietta.kaszkin@h-r-s.biz

Abstract

M. Fukuda, K. Morozumi, T. Oikawa, M. Motokawa, T. Usami, A. Yoshida and G. Kimura

¹Department of Internal Medicine and Pathophysiology, Nagoya City University Graduate School of Medical Sciences, and ²Kidney Center, Nagoya Daini Red Cross Hospital, Nagoya, Japan
We present the case of a 69-year-old man with nephrotic syndrome and renal insufficiency, who developed lobular glomerulonephritis. An electron microscopy examination of a renal biopsy showed microtubular structures of 24 nm in diameter in the subendothelial space and the paramesangial area. These deposits were PAS-positive and Congo red-negative, and revealed predominantly positive staining for k light chain. There was no evidence of diseases with highly organized glomerular deposits, such as amyloidosis, cryoglobulinemia, systemic lupus erythematosus or paraproteinemia. Therefore, the patient was diagnosed to have immunotactoid glomerulopathy (ITG). During a seven-year course he has not developed any disease known to be associated with organized glomerular immune deposits. Hence, we believe ITG occurred as a primary glomerular disease in this case. We also highlight cases of ITG with microtubular deposits that have been reported in Japan, compare these cases to previous reports, and show that the characteristics of the Japanese cases are male predominance; a high incidence of membranoproliferative glomerulonephritis (MPGN); a low incidence of monoclonal gammopathy and hematological malignancies and a higher incidence of hypocomplementemia.
Correspondence to:
M. Fukuda, MD Department of Internal Medicine and Pathophysiology Nagoya City University Graduate School of Medical Sciences Mizuho-ku, Nagoya 467-8601, Japan
Email: m-fukuda@med.nagoya-cu.ac.jp

Abstract

A. Raff, T. Hebert, J. Pullman and M. Coco

¹Renal Division, and ²Department of Pathology, Montefiore Medical Center, Albert Einstein College of Medicine, Bronx, NY, USA
The prognosis for adults with acute post-streptococcal glomerulonephritis (PSGN) who present with crescentic glomerulonephritis and nephrotic proteinuria is not known. We report a patient with rapidly progressive glomerulonephritis and nephrotic-range proteinuria following acute pharyngitis, in whom serologic and kidney biopsy findings led to a diagnosis of PSGN. The patient was treated with corticosteroids and anti-hypertensive medications resulting in improvement in renal function and decrease in proteinuria. These results suggest that aggressive treatment of crescentic PSGN with nephrotic syndrome can result in a favorable outcome.Correspondence to:
M. Coco, MD Montefiore Medical Center 111 East 210th Street Bronx, NY 10467, USA
Email: mcoco@montefiore.org

Abstract

M. Almansori, T. Kovithavongs and M.U. Qarni

¹Department of Medicine and ²Division of Nephrology, University of Alberta, Edmonton, Alberta, Canada
Selective cyclooxygenase-2 (COX-2) inhibitors are relatively newer antiinflammatory drugs that produce comparable antiinflammatory and analgesic effects to the nonselective nonsteroidal antiinflammatory drugs (NSAIDs); but with fewer sympto-matic gastric and duodenal ulcers. Limited data are available concerning the toxicity associated with COX-2 inhibitors outside the gastrointestinal tract. The NSAIDs have been known for their nephrotoxic potentials including minimal-change disease (MCD) with interstitial nephritis. Although the recent data suggests that COX-2 inhibitors may have the same adverse renal effect as NSAIDs, there is only one case report describing minimal change disease and acute interstitial nephritis (AIN) associated with a COX-2 inhibitor, celecoxib. We are reporting a case of MCD and acute tubular necrosis (ATN) but without interstitial nephritis in a patient treated with celecoxib. Although the proteinuria in our patient resolved completely after discontinuation of celecoxib, the renal function did not. We suggest that heightened suspicion of this side effect of COX-2 inhibitors should be maintained in all patients taking this class of drugs who present with nephrotic syndrome.Correspondence to:
M. U. Qarni, MD, FRCPC, FACP 11-107F Clinical Sciences Building University of Alberta Edmonton, AB T6G 2G3, Canada
Email: Uwais.qarni@ualberta.ca

Abstract

J.-B. Esteve, V. Launay-Vacher, I. Brocheriou, A. Grimaldi and H. Izzedine

¹Department of Medicine and ²Division of Nephrology, University of Alberta, Edmonton, Alberta, Canada
We report a case of biopsy-proven acute interstitial nephritis (AIN) in a 50-year-old diabetic woman, who had been treated with celecoxib for 4 weeks before presentation. She presented with clinical findings of renal proximal tubulopathy, aseptic leukocyturia and acute renal failure. A kidney biopsy specimen showed AIN with intense tubuli and eosinophilic infiltrate in the interstitium. She recovered normal renal function two weeks after cessation of celecoxib and use of a corticosteroid. A review of the literature yielded eight cases of COX-2 inhibitor-associated AIN with a biopsy-proven diagnosis. Among the reported cases, AIN was diagnosed after an average of 8.3 months of therapy (SD 12 months, range 3 days – 3 years) with 25 mg rofecoxib or 200 mg celecoxib daily. Common symptoms included asthenia, anorexia, nausea and vomiting. The classic triad of fever, rash and eosinophilia was uncommon. Typical laboratory features included hematuria, proteinuria, eosinophilia. Renal failure was common at the time of diagnosis. Mean serum creatinine levels were 0.86 ± 0.11 mg/dl, 5.66 ± 3.50 mg/dl and 1.15 ± 0.24 before treatment, at time of diagnosis and 1 – 2 months after COX-2 inhibitor withdrawal, respectively. Three patients required emergency hemodialysis. After cessation of COX-2 inhibitor treatment, patients recovered completely with a normalized serum creatinine level after one to two months. Management consisted of withdrawal of the COX-2 inhibitor drug and in four patients, corticosteroid therapy was well-tolerated and may have been beneficial.Correspondence to:
H. Izzedine, MD
Department of Nephrology
Pitié SalpêtriPre Hospital
47-83 Boulevard de l’Hôpital
75013 Paris, France
Email: hassan.izzedine@psl.ap-hop-paris.fr

Abstract

S. Chinen, T. Tana, K. Kohagura, M. Yamazato, K. Iseki and S. Takishita

Department of Investigative Medicine, Cardiovascular Medicine, Nephrology and Neurology, Third Department of Internal Medicine, ¹University of the Ryukyus, ²Tana Medical Clinic and ³Dialysis Unit, University Hospital of the Ryukyus, Okinawa, Japan
A 16-year-old Japanese girl was admitted to our hospital on February 27, 2001, for acute renal failure. She had not shown proteinuria or hematuria in any school examination through 2000. The first renal biopsy specimen showed focal segmental glomerulosclerosis and tubulointerstitial change. Electron microscopy showed numerous myeloid bodies in the glomerular epithelium suggesting the diagnosis of Anderson-Fabry disease. After electron microscopy, we measured WBC a-galactosidase A, which was slightly decreased to 36.1 nmol/mgP/h (normal: 49.8 – 116.4). WBC a-galactosidase A levels for other family members were 74.3 for the mother, 4.8 for the father, 45.6 for the elder sister, and 16.3 for the younger sister. During the follow-up, she had two episodes of nephrotic syndrome, which responded well to steroid therapy. Both second and third renal biopsy showed numerous myeloid bodies by electron microscopy. A 52-year-old man, the father of the case one patient, was admitted for renal biopsy because of proteinuria and low levels of WBC a-galactosidase. Biopsy specimen showed typical changes under light microscopy and typical myeloid bodies by electron microscopy. Our cases underscore the importance of electron microscopy when examining the biopsy specimen and suggest that undiagnosed Anderson-Fabry disease may be present, in particular on chronic dialysis.Correspondence to:
K. Iseki, MD
Dialysis Unit
University Hospital of the Ryukyus
207 Uehara, Nishihara, Okinawa 903-0215, Japan
Email: chihokun@med.u-ryukyu.ac.jp

Abstract

E. Svarstad¹, L. Bostad², Ø. Kaarbøe¹, G. Houge³, C. Tøndel⁴, P.T. Lyngdal⁵ and B.M. Iversen¹

¹Renal Research Group, Institute of Medicine, ²The Gade Institute, Department of Pathology, ³Department of Medical Genetics, ⁴Division of Paediatrics, Department of Clinical and Molecular Medicine, University of Bergen, Bergen, and ⁵Department of Nephrolo
We describe a man and a woman with Fabry’s disease. Renal biopsies showed late and early stages respectively of focal and segmental glomerulosclerosis (FSGS) and vascular changes. Clinically the hemizygous patient had advanced renal disease with nephrotic range proteinuria and serum creatinine 122 µmol/l. The female carrier had minimal albuminuria, borderline GFR with a normal serum creatinine, acroparesthesias, moderate fatigue, tinnitus and headache accompanied by ischemic cerebral lesions. Enzyme replacement therapy (ERT) was initiated according to our Fabry protocol, partly due to the renal morphologic findings. We conclude that FSGS and vascular changes may be an early morphologic finding in Fabry’s disease, even in patients with subtle albuminuria. The potential role of FSGS as a marker of progressive renal disease in some Fabry patients is discussed. As FSGS and vascular changes obviously may exist across a wide range of clinical presentations and have potential prognostic implications, we suggest that a renal biopsy should be performed prior to enzyme replacement therapy in all adult Fabry patients with proteinuria of various levels. Efforts should be made to develop a scoring system to evaluate potential histologic markers. Protocol biopsies may have therapeutic implications and may provide valuable information in the evaluation of start and dosing of ERT.Correspondence to:
E. Svarstad

Renal Research Group

Medical Department

5021 Haukeland University Hospital, Norway
Email: einar.svarstad@helse-bergen.no

Abstract

G. Sahin, M.F. Acikalin and A.U. Yalcin

Departments of ¹Nephrology and ²Pathology, Osmangazi University Medical School, Eskisehir, Turkey
Anemia is an important cause of morbidity in patients suffering from chronic renal failure, and erythropoietin is a milestone of anemia treatment. Various factors may cause erythropoietin resistance. Herein, we describe the case of 32-year-old man who presented with anemia and weakness. He developed progressive renal failure secondary to recurrent kidney stones. One year before admission, he developed anemia for which he had been treated with erythropoietin. However, the anemia persisted. Examination of bone marrow biopsy specimen showed that the marrow was extensively replaced with oxalate crystals and fibrous connective tissue with severe decrease of hematopoietic cells. To the best of our knowledge, our patient represents the first case in the literature describing the association between the oxalate deposition and EPO resistance.Correspondence to:
G. Sahin, MD Yenikent Mah 60 D Blok D: 4 26050 Yenikent/ Eskisehir, Turkey
Email: garipsahin@superonline.com

Abstract

J. Guitard, N. Kamar, M. Mouzin, J.S. Borde, T. Tran-Van, D. Durand and L. Rostaing

¹Department of Nephrology, Dialysis and Transplantation, ²Department of Urology, and ³Service d’Explorations Fonctionnelles Physiologiques, CHU Rangueil, Toulouse Cedex, France
We report on the first case of acute renal failure related to obstructive urinary tract lithiasis involving sulfadiazine crystals in a kidney transplant recipient. This patient had disseminated toxoplasmosis which was treated by sulfadiazine (4 g/day) and pyrimethamine (50 mg/day). In the fourth week of anti-toxoplasmosis therapy, he presented with obstructive acute renal failure: the plasma creatinine level increased from 220 mmol/l to 547 mmol/l. A percutaneous pyelography was conducted showing the presence of a lithiasis located at the junction between the graft ureter and the bladder. Six days later, he underwent surgery to retrieve an orange-colored, friable stone. Its spectrophotometric analysis confirmed that the stone consisted of N-acetyl sulfadiazine crystals.
Correspondence to:
Prof. L. Rostaing
Department of Nephrology
Dialysis and Transplantation
CHU Rangueil
1 avevue jean PoulhPs, TSA 50032
31059 Toulouse Cedex 9, France
Email: rostaing.l@chu-toulouse.fr

Abstract

R. Farag, J.A. Schulak, F.W. Abdul-Karim and J.K. Wasman

¹Department of Pathology, and ²Department of Surgery, Case Western Reserve University School of Medicine and University Hospitals of Cleveland, Cleveland, OH, USA
Angiosarcoma in the setting of immunosuppressed renal transplant recipients is exceedingly rare. In this report, we describe the occurrence of angiosarcoma arising at an arteriovenous fistula site of a 39-year-old renal transplant recipient that clinically mimicked a thrombosed aneurysm. These tumors are histologically high-grade and clinically aggressive malignancies. They have a predilection for arteriovenous fistula sites. The literature on this uncommon entity is reviewed and possible histogenesis is discussed. Correspondence to:
J. Wasman, MD
Department of Pathology
Case Western Reserve University
School of Medicine and University Hospitals of Cleveland
11100 Euclid Avenue
Cleveland, OH 44106, USA
Email: jay.wasman@uhhs.com

Abstract

M. Senatore, C. Sapio, A. Di Somma, G. Caporale, A. Russo and G.C. Gallo

Abstract

R. Rault

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Volume 63, No. 5/2005(May)