Volume 67, No. 5/2007(May)
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 Clinical Nephrology
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Review
Pharmacokinetics and antimicrobial dosing adjustment in critically ill patients during continuous renal replacement therapy
Abstract
D. Kuang, A. Verbine and C. Ronco
1Department of Nephrology, Dialysis and Transplantation, San Bortolo Hospital, Vicenza, Italy, 2Department of Nephrology, Huashan Hospital, Fudan University, Shanghai, P.R. China
Appropriate antimicrobial therapy poses one of the greatest challenges during the management of a septic patient in the intensive care unit (ICU). Acute renal failure (ARF) is a common complication of sepsis and often occurs as a component of multiple organ dysfunction syndrome. Continuous renal replacement therapy (CRRT) is increasingly used as an effective extracorporeal blood purification therapy in this critically ill patient population. Available data demonstrate that sepsis, ARF and different modalities of CRRT may have profound effects on the pharmacokinetics and pharmacodynamics of various antimicrobial agents used in the ICU. Guidelines for antimicrobial prescription which will fit the individual patient undergoing a particular method of treatment are still unavailable. Understanding the principles of drug removal by CRRT and pharmacokinetics of various agents can help to modify the drug dosage and dosing intervals for individualized therapy. Meanwhile, monitoring the drug serum concentration is still mandatory whenever clinically feasible.Correspondence to:
Prof. C. Ronco Department of Nephrology, Dialysis and Transplantation San Bortolo Hospital Via Rodolfi 37 36100 Vicenza, Italy
Email: cronco@goldnet.it
Originals
Single daily dose of cyclosporine in patients with primary glomerulonephritis and nephrotic syndrome
Abstract
F.M. Rasche, F. Keller, G. Kunze, B. Boesler and D. Czock
Medical Department, Division of Nephrology, University Hospital Ulm, Germany
Aims: Single daily dose cyclosporine (SDD-CsA) might be a new option providing comparable efficacy, increased compliance and less nephrotoxicity compared to standard twice-daily dose cyclosporine (TDD-CsA). The aim of this trial was to prove the feasibility of SDD-CsA as primary and secondary maintenance therapy in patients with nephrotic syndrome. Methods: We treated 25 adult patients with nephrotic syndrome and chronic primary glomerulonephropathy with SDD-CsA for a period of 12 months or more. 12 patients were pre-treated with twice-daily dose cyclosporine (TDD-CsA) and were then switched secondarily to a single daily dose after a median period of 8 months (sSDD-CsA). 13 patients were treated primarily with single daily dose cyclosporine (pSDD-CsA). Results: In primary SDD-CsA patients, proteinuria decreased significantly from 9.2 – 0.8 g/l (p = 0.02) and serum protein increased significantly from 54 – 71 g/l (p = 0.03) during the study period. In secondary SDD-CsA patients, serum protein increased further (64 – 69, p = 0.04) after switching to SDD-CsA. In secondary SDD-CsA patients, the median total daily CsA dose was significantly lower (200 mg) with SDD-CsA compared to previous twice-daily dosing (300 mg, p = 0.01). Serum creatinine did not differ significantly before and after therapy and between the groups. Conclusions: SDD-CsA is effective in patients with nephrotic syndrome as primary and secondary maintenance therapy. SDD-CsA allows for significantly lower total daily doses, probably with less nephrotoxicity.Correspondence to:
Prof. F. Keller University Hospital Ulm Medical Department Division of Nephrology Robert-Koch-Straße 8 89081 Ulm, Germany
Email: frieder.keller@uni-ulm.de
Originals
Renal pathological change in patients with Type 2 diabetes is not always diabetic nephropathy: a report of 52 cases
Abstract
F. Huang, Q. Yang, L. Chen, S. Tang, W. Liu and X. Yu
1Department of Nephrology, The First Affiliated Hospital, 2Department of Endocrinology and Metabolism, The Second Affiliated Hospital, Sun Yat-sen University, Guangzhou, China
Aims: The present study examined the relationship between clinical features and renal histological changes in the Type 2-diabetic patients and evaluated the usefulness of renal biopsy in the diagnosis of diabetic versus non-diabetic kidney disease. Methods: 52 patients with Type 2-diabetic mellitus were retrospectively analyzed for differential clinical, laboratory features and pathological characteristics including overt proteinuria (> 0.5 g/day), elevated serum creatinine and/or the development of hematuria. Results: Of 52 patients, 20 cases (38.5%) showed no detectable diabetic lesions and, thus, were diagnosed as non-diabetic renal disease (NDRD), while 32 patients (61.5%) exhibited diabetic nephropathy. Interestingly, while 29 patients showed diabetic nephropathy (DN) alone, NDRD was also found in 3 patients with DN. Clinically, 24 out of 52 patients (46.16%) had a diagnosis consistent with the pathological findings, while 10 (19.23%) were diagnosed incorrectly. Compared to NDRD patients, patients with DN had prolonged diabetic history with or without retinopathy, while 25% of patients with NDRD exhibited mesangial proliferative glomerulonephritis. Conclusions: NDRD was a common feature in Type 2-diabetic patients with renal involvement. The absence of retinopathy and short periods of diabetic history may be useful indicators for diagnosis of NDRD clinically.Correspondence to:
X. Yu, MD Department of Nephrology The First Affiliated Hospital Sun Yat-sen University, Guangzhou 510080, China
Email: yuxq@mail.sysu.edu.cn
Originals
Tonsillectomy in the treatment of pediatric Henoch-Schönlein nephritis
Abstract
C.N. Inoue, Y. Chiba, T. Morimoto, T. Nishio, Y. Kondo, M. Adachi and S. Matsutani
1Department of Pediatrics, Red Cross Sendai Hospital, 2Department of Pediatrics, Tohoku University School of Medicine, 3Department of Otolaryngology, Red Cross Sendai Hospital, Sendai, Japan
The exact pathophysiology of HSN remains to be elucidated. Hence, a therapeutic strategy that enables curative treatments for all the various grades of HSN patients has yet to be established. We report our experience performing tonsillectomy combined with steroid therapy for 16 pediatric proteinuric Henoch-Schönlein nephritis (HSN) patients. All patients exhibited hematuria and proteinuria in their first HSN attack with the mean age of onset 7.7 years (range 4.75 – 13.9 years). Nine patients were diagnosed with clinically severe HSN presenting with massive proteinuria (> 1 g/m2/day). Renal biopsy findings performed in 6 patients were Grade II (3), Grade III (2) and Grade IV (1) according to the International Study of Kidney Diseases in childhood classification. Tonsillectomy was performed after 1 – 4 cycles of methylprednisolone pulses during oral prednisolone (0.5 – 1.5 mg/kg/day) therapy. In 2 patients, oral cyclophosphamide therapy was added before the tonsillectomy. The interval between the onset of HSN and tonsillectomy was 97.4 ± 24.5 days (range 27 – 424 days). In all patients, proteinuria had disappeared by 6 months after the tonsillectomy and the urine findings had normalized. The interval between therapy initiation and complete remission was 9.6 ± 2.0 months (range 2 – 26 months). Over follow-up periods of 4.9 ± 0.6 years (range 2.2 – 9.3 years), no recurrences of Henoch-Schönlein purpura or HSN were observed. There was a significant correlation between early tonsillectomy performance and decreased time until normalization of the urine findings, indicating that the tonsils may have pivotal roles in the initiation and progression of HSN. Their elimination might promote the reversal of nephritis. Although this study is retrospective, we suggested that tonsillectomy at an early stage of HSN may be beneficial by shortening the period of illness and contributing to clinical recovery. Randomized controlled trials will be needed to confirm this supposition. Correspondence to:
C.N. Inoue, MD, PhD Department of Pediatrics Red Cross Sendai Hospital 2-43-3, Yagiyamahon-cho, Taihaku-ku, Sendai 982-8501, Japan
Email: chnagano@sendai.jrc.or.jp
Originals
The continuous erythropoietin receptor activator (C.E.R.A.) corrects anemia at extended administration intervals in patients with chronic kidney disease not on dialysis: results of a phase II study
Abstract
R. Provenzano, A. Besarab, I.C. Macdougall, D.H. Ellison, A.P. Maxwell, W. Sulowicz, M. Klinger, B. Rutkowski, R. Correa-Rotter and F.C. Dougherty on behalf of the BA16528 Study Investigators
1Division of Nephrology, St. John Hospital, Detroit, MI, USA, 2Division of Nephrology and Hypertension, Henry Ford Hospital, Detroit, MI, USA, 3Renal Unit, Cheyne Wing, King’s College Hospital, London, UK, 4Division of Nephrology and Hypertension, Oregon Health and Science University, Portland, OR, USA, 5Nephrology Unit, Belfast City Hospital, Belfast, Northern Ireland, 6Department of Nephrology, University Hospital, Krakow, Poland, 7Department of Nephrology and Transplantation Medicine, Medical University, Wroclaw, Poland, 8Clinic of Nephrology, Medical University, Gdansk, Poland, 9Instituto Nacional De Ciencias Médicas y Nutrición Salvador Zubirán, Mexico City, Mexico and 10Pharma Development, F. Hoffmann-La Roche Ltd., Basel, Switzerland
Aim: This study was designed to assess the potential of the continuous erythropoietin receptor activator (C.E.R.A.) to correct anemia at extended administration intervals in erythropoiesis-stimulating agent-naïve patients with chronic kidney disease (CKD) not on dialysis and to determine its optimal starting dose. Methods: Patients were assigned to subcutaneous C.E.R.A. at 3 doses: 0.15, 0.30 and 0.60 µg/kg/wk. During the first 6 weeks, dose adjustments for efficacy were not permitted in order to assess dose response. Within each of the 3 dose groups, patients were randomized to receive C.E.R.A. QW, Q2W or Q3W; the total dose during the first 6 weeks was the same for a particular dose group across the frequency subgroups. During the next 12 weeks, dose was adjusted according to predefined hemoglobin (Hb) criteria. The primary efficacy parameter was change in Hb over 6 weeks, estimated from regression analysis between baseline and the point at which the patient received a dose change or blood transfusion. It therefore provided an estimate of Hb increase based on starting dose. Other endpoints included Hb response rate (proportion of patients with a Hb increase >= 1.0 g/dl on 2 consecutive occasions). A 1-year extension period investigated long term tolerability and efficacy. Results: A dose-dependent relationship was noted in the mean change in Hb from baseline over 6 weeks (p < 0.0001), independent of administration schedule (p = 0.9201). There was also a significant relationship between Hb change and median serum C.E.R.A. concentration (p < 0.0001). Erythropoietic responses were sustained in all groups with mean changes from baseline in Hb > 1.2 g/dl observed at doses ³ 0.30 mg/kg/wk. Hb response rate increased with increasing dose: 67, 72 and 90% with C.E.R.A. 0.15, 0.30 and 0.60 µg/kg/wk, respectively. Generally, the median Hb response time was faster with increasing dose (89, 43 and 31 days, respectively). Response was unrelated to administration frequency. Stable Hb concentrations were maintained throughout the 1-year extension period. C.E.R.A. was generally well tolerated, and the most common adverse events were hypertension, urinary tract infection and renal failure. Conclusions: C.E.R.A. corrected anemia and maintained sustained and stable control of Hb over 1 year. These results suggest that 0.60 mg/kg subcutaneous C.E.R.A. given twice monthly is a suitable starting dose for further investigation in Phase III studies in patients with CKD not on dialysis.Correspondence to:
Dr. R. Provenzano Division of Nephrology St. John Hospital 22201 Moross Road, Suite 150 Detroit, MI 48236, USA
Email: robert.provenzano@stjohn.org
Case Reports
Retroperitoneal hematoma compressing a single functioning kidney: an unusual cause of obstructive renal failure
Abstract
M. Monge, I. Vaida, S.S. Modeliar, A. Solanilla, N. Airapetian, C. Presne, R. Makdassi, A. Fournier and G. Choukroun
1Department of Nephrology, Internal Medicine and Intensive Care Unit, 2Hematology, University Hospital, Amiens, France
We report a case of a retroperitoneal hematoma occurring in a patient under anticoagulation therapy for deep-venous thrombosis and presenting as an anuric acute renal failure. A coexisting polycythemia vera led to misdiagnosis that could have been life-threatening. A woman, known for polycythemia vera and a single functioning right kidney, was admitted with mild abdominal pain in a context of recent deep venous thrombosis under low-molecular weight heparin. Clinical examination revealed hepatomegaly associated with polycythemia vera. Biochemical evaluation disclosed an acute renal failure, and renal ultrasonography showed no dilation of the renal pelvis. Retroperitoneal hematoma resulted in shock, progressive anemia and obstructive renal failure, related to renal pelvic compression. A right renal indwelling catheter was introduced to restore urine flow after one hemodialysis session, and an inferior vena cava filter was placed because of anti-coagulation contra-indication. However, pulmonary embolism occurred, so that oral anticoagulants were introduced. The hematoma resorbed spontaneously, and a year after this episode, the patient is still alive and well. Retroperitoneal hematoma is a rare cause of obstructive acute renal failure and a life-threatening complication of anti-coagulation therapy.Correspondence to:
M. Monge, MD Department of Nephrology Internal Medicine and Intensive Care Unit Amiens University Hospita Av R Laennec 80054 Amiens, France
Email: mongematt@yahoo.fr
Case Reports
An unusual cause of acute renal failure in a kidney transplant recipient: Salmonella enteritidis post-infectious glomerulonephritis
Abstract
A. Pillet, J. Guitard, M. Mehrenberger, N. Kamar, C. Orfila, D. Ribes, A. Modesto and L. Rostaing
1Department of Nephrology, Dialysis and Multiorgan Transplantation and 2Department of Histopathology, CHU Rangueil, Toulouse, France
Background: Salmonella enteritidis-associated acute renal failure has often been described and is usually a result of dehydration or of rhabdomyolysis. A few cases of acute renal failure with glomerular syndrome, caused by S. enteritidis infection, have been reported in the literature, but none have been proven by histological findings. Methods: Herein, we report on a case of S. enteritidis-related glomerulonephritis that occurred in a 42-year-old male transplant recipient. He was admitted with fever, signs of urinary infection, diarrhea, and nephritic syndrome, i.e. edema, hypertension, increase in serum creatinine, microscopic hematuria, proteinuria. His urine culture tested positive for S. enteritidis. Results: Under light microscopy, the graft biopsy showed proliferative and exudative endocapillary glomerulonephritis. In addition, there was polymorphonuclear infiltration of the interstitium, and extra-capillary proliferation in one glomerulus. Immunofluorescence showed granular deposits of C3 in the mesangium. Electron microscopy showed electron-dense deposits typical of humps. He fully recovered on a double antibiotic therapy that included ofloxacin and amikacin. Conclusion: Although acute renal failure related to non-typhoidal Salmonella infections are often related to dehydration or rhabdomyolysis, this case report shows that it might also be related to immune complex-mediated glomerulonephritis manifesting as nephritic syndrome.
Correspondence to:
Prof. L. Rostaing Department of Nephrology, Dialysis and Transplantation CHU Rangueil, 1 avenue Jean Poulhès, TSA, 50032 31059 Toulouse Cedex 9, France
Email: rostaing.l@chu-toulouse.fr
Case Reports
Dialysis catheter-induced superior vena cava syndrome and downhill esophageal varices
Abstract
M.W. Greenwell, S.L. Basye, S.S. Dhawan, F.D. Parks and S.R. Acchiardo
1Department of Internal Medicine, Division of Nephrology, University of Tennessee Health Science Center, 2Department of Radiology, Methodist University Hospital, Memphis, TN, USA
Superior vena cava stenosis is a well-documented complication of central venous dialysis catheters. Rarely, this obstruction can lead to the formation of downhill esophageal varices. We present a case of esophageal varices as a complication of dialysis catheter-induced superior vena cava stenosis, which became symptomatic after the placement of an upper extremity arteriovenous graft and resolved with percutaneous angioplasty and stenting of the superior vena cava stricture.Correspondence to:
M.W. Greenwell, MD University of Tennessee Health Science Center Department of Internal Medicine Division of Nephrology 920 Madison Avenue, Suite 200 Memphis, TN 38103, USA
Email: mandsgreen@excite.com
Letters to the Editor
A case of a pregnant woman developing systemic lupus erythematosus during pregnancy
Abstract
S. Matsuo, E. Uchida, S. Shimajiri and G. Nishihara
Letters to the Editor
Chylous ascites and chylothorax due to membranous nephropathy
Abstract
H.B. Colak, T. Alici, H. Tekce, D. Öz, A. Erol, F. Aras and S. Kursat
