Volume 60, No. 1/2003(July)
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 Clinical Nephrology
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Review
Molecular mechanisms modifying the peritoneal membrane exposed to peritoneal dialysis
Abstract
G. Gillerot and O. Devuyst
Division of Nephrology, Université Catholique de Louvain Medical School, Brussels, Belgium
Over time, a significant proportion of patients an peritoneal dialysis (PD) develop an increased permeability for small solutes, which induces a faster absorption of glucose, and ultrafiltration failure by early dissipation of the osmotic gradient. Vascular proliferation and vasodilatation of preexisting vessels might represent the structural basis for increased effective peritoneal surface area encountered in these PD patients. Animal models have shown that local release of growth factors and nitric oxide in the peritoneal membrane (PM) may lead to the development of areas of neovascularization and/or submesothelial fibrosis. Long-term exposure to conventional, glucose-based dialysis fluids plays a central role in the pathogenesis of these structural modifications. Glucose degradation products and reactive carbonyl species, which are present both in glucose-based dialysates and uremic plasma, accelerate the formation of the advanced glycation end products in the PM, which may in turn initiate a range of cellular responses including stimulation of monocytes, secretion of inflammatory cytokines, proliferation of vascular smooth muscle cells, stimulation of growth factors, and secretion of matrix proteins. The changes in the PM may also be potentiated by uremia and hyperglycemia per se. These new insights into the molecular mechanisms operating in the PM have provided rationale for novel therapeutic strategies including the development of glucose-free PD solutions and two-chamber bags.
Originals
Clinical correlates of serial urinary membrane attack complex estimates in patients with idiopathic membranous nephropathy
Abstract
D.C. Cattran, R. Wald, P.E.C. Brenchley and B. Coupes for the North American Nephrotic Syndrome Group and the Genes, Gender and Glomerulonephritis Group
1Department of Medicine, Toronto General Hospital/University Health Network and University of Toronto, Canada and 2Renal Research, Manchester Institute of Nephrology and Transplantation, Manchester Royal Infirmary, Oxford Head, Manchester, UK
Aims: The membrane attack complex (MAC) plays a key role in the pathogenesis of experimental membranous nephropathy. However, the clinical significance of urinary MAC (UMAC) excretion in human idiopathic membranous nephropathy (IMGN) and other proteinuric glomerulopathies is not fully elucidated. Patients and methods: We studied 16 patients with IMGN and 4 with focal segmental glomerulosclerosis (FSGS) who participated in clinical trials. Serial measures of UMAC, proteinuria and serum indices of renal function were conducted over the 26 weeks of treatment. Patients with UMAC excretion at treatment outset were identified as UMAC (+). We compared UMAC (+) and UMAC (?) patients with respect to several parameters at treatment initiation and study completion including age, disease duration, serum creatinine, creatinine clearance and proteinuria. In the UMAC(+) group we compared changes in UMAC values over time with patient outcome. Results: There were no demographic or clinical characteristics at presentation and study completion that distinguished the 8 UMAC (+) patients from the 12 UMAC (?) patients. As well, UMAC positivity did not predict response to therapy. Among the 8 UMAC (+) patients, 4 (3 IMGN and 1 FSGS) responded to therapy and in all cases, UMAC became undetectable. Non-responders to therapy (2 IMGN and 2 FSGS) continued to excrete UMAC at the conclusion of treatment. Initial UMAC levels of responders and non-responders were similar. Conclusions: UMAC levels parallel proteinuria not only in IMGN but also in FSGS patients. Immunomodulation may reduce glomerular formation of MAC in IMGN. In both histologic subtypes, the reduction in filtered protein may diminish the activation of MAC at the tubulointerstitial interface. However, the clinical utility of measuring UMAC is limited by its low prevalence, the absence of histopathologic specificity and its equivocal role in predicting outcome.
Originals
Combined converting enzyme inhibition and angiotensin receptor blockade reduce proteinuria greater than converting enzyme inhibition alone: insights into mechanism
Abstract
J. Panos, M.F. Michelis, M.V. DeVita, R.H. Lavie and B.M. Wilkes
Nephrology Section, Department of Medicine, Lenox Hill Hospital and
The New York University School of Medicine, New York, NY, USA
Patients with various renal diseases receiving an angiotensin-converting enzyme inhibitor (CEI) were enrolled in a protocol to determine whether adding an angiotensin type 1 receptor blocker (ARB) reduces urinary protein excretion (UPE). All patients had significant proteinuria (range 517 – 8,562 mg/24 h) despite administration of CEI for at least 4 weeks. Following baseline measurements, losartan (50 mg/d) was started and testing was repeated at 1 month. Compared with CEI alone, combined CEI plus ARB reduced UPE by 45 ± 8% (p < 0.005). Compared with CEI alone, CEI + ARB lowered UPE in each patient independent of baseline protein excretion or renal diagnosis. Reduction in proteinuria occurred independent of changes in mean arterial blood pressure (MAP), suggesting that the mechanism involved local changes in glomerular dynamics. If renal angiotensin II (ANG II) formation occurred despite CEI, the ANG II formed would suppress plasma renin activity (PRA), and adding an ARB would cause PRA to rise. In 7 of 10 subjects, addition of ARB to CEI increased PRA (p < 0.03) suggesting that intrarenal ANG II formation occurred in CEI-treated subjects. As a second marker of ANG II tissue activity, we measured the effects adding ARB on plasma aldosterone (ALDO). In 9 of 10 subjects, ALDO was acutely lowered (p < 0.009) suggesting that ANG II levels were incompletely blocked by CEI. We conclude that: combined CEI and ARB reduces UPE greater than CEI alone; reduction in proteinuria is independent of changes in MAP or renal diagnosis; and the additive effects of CEI and ARB are due at least in part to greater inhibition of ANG II action at the tissue level in the kidneys and adrenal glomerulosa.
Originals
Daily weight gain and protein catabolic rate are lower over the long interdialytic interval
Abstract
A. Stragier and M. Jadoul
Department of Nephrology, University Clinic St-Luc, Université Catholique de Louvain, Brussels, Belgium
Background: The interdialytic weight gain (IDWG) and protein catabolic rate (PCR), expressed per 24 hours (daily), are usually assumed to be stable over the week in chronic hemodialysis (HD) patients. Methods: We studied different HD patient groups at different time points (study 1 in 1993: n = 48, study 2 in 1999: n = 16, study 3 in 2000: n = 112). Daily IDWG (calculated from post- and pre-dialysis body weight and interdialytic interval) and nPCR (calculated from kinetic modeling) were compared over short (2 days) and long (3 days) intervals. Results: In all groups of HD patients studied, both daily IDWG and nPCR were significantly (p < 0.05) lower (IDWG by 7 ? 15%, nPCR by 5 ? 6%) over long than short interdialytic intervals. This difference was observed whether or not blood sampling was planned after the long interval. This suggests selfrestriction of dietary intake over the long interdialytic interval. Conclusions: Daily IDWG and nPCR are lower over the long interdialytic interval. Studies should thus define or even standardize the period of time over which IDWG and nPCR are calculated.
Originals
Effects of vitamin supplementation on microcirculatory disturbance in hemodialysis patients without peripheral arterial disease
Abstract
M. Sato, Y. Matsumoto, H. Morita, H. Takemura, K. Shimoi and I. Amano
1Department of Dialysis Therapy, Social Insurance Chukyo Hospital, Nagoya, 2School of Nursing, University of Shizuoka, and
3Institute for Environmental Sciences, University of Shizuoka, Shizuoka, Japan
Aims: Dysfunctional endothelium caused by oxidative stress is thought to play a role in pathogenesis of a variety of conditions including atherosclerosis. We investigated whether a microcirculatory disturbance in hemodialysis (HD) patients was associated with increased oxidative stress and endothelial injury. Patients and methods: Transcutaneous oxygen tension (TcPO2) on the dorsum of the foot at rest was measured as a marker of microcirculation in 33 patients undergoing HD without clinical manifestations of peripheral arterial disease and 20 healthy controls. Furthermore, in order to examine whether TcPO2 was affected by antioxidants, oral supplementation with a combination of vitamin C (200 mg daily) and vitamin E (600 mg daily) was administered for 6 months to 8 patients with microcirculatory disturbance (TcPO2 values of 50 mmHg or less). Serum biochemical parameters including vitamins were also measured. Results: Mean TcPO2 value was significantly lower in HD patients than in control subjects (47.9 ± 13.5 mmHg versus 62.4 ± 11.9 mmHg, p < 0.001). After vitamin supplementation, TcPO2 values remarkably increased (40.6 ± 10.0 mmHg versus 57.4 ± 6.5 mmHg, p < 0.005). Serum vitamin C and vitamin E levels increased significantly as well, while serum levels of thrombomodulin, a marker of endothelial injury, and thiobarbituric acid reactants, a marker of lipid peroxidation, were significantly decreased in comparison with those before supplementation. Conclusions: Our results suggest that the microcirculatory disturbance in HD patients seems to be associated with endothelial damage caused by oxidative stress. Combined supplementation with vitamin C and vitamin E may be of clinical benefit in improving the cutaneous microcirculation by reducing oxidative stress.
Originals
Treatment of ?swing point stenoses? in hemodialysis arteriovenous fistulae
Abstract
A. Falk, V. Teodorescu, W.Y.W. Lou, J. Uribarri and J.A. Vassalotti
Departments of 1Radiology, 2Surgery, 3Biomathematical Sciences, and
4Medicine, Mount Sinai-NYU Medical Center, New York, NY, USA
Aim: This is a retrospective study of percutaneous transluminal balloon angioplasty (PTA) efficacy for treatment of surgical vein mobilization site (?swing point?) stenoses in hemodialysis arteriovenous fistulae (AVF) that fail to mature or are poorly functioning. Method: Between February 1, 1999, and February 28, 2001, 65 non-maturing or poorly functioning AVF were studied in 63 consecutive hemodialysis patients (30 male, 33 female, aged 26 ? 92 years). All AVF underwent contrast angiography to study the inflow artery, AVF, outflow and central veins. PTA of stenotic sites was performed to initiate or restore AVF function. Results: Seventy-eight venous and 2 arterial stenoses were found and treated with PTA in the 65 AVF. All PTA were technically successful. A total of 55 stenoses were identified in the vein at the site of surgical mobilization (?swing point?). Additionally, 19 cephalic and 4 central venous stenoses were found. During the study, 13 AVF underwent repeat PTA at the ?swing point?. Of the 65 AVF treated, 50 were being successfully used as an access site, 4 AVF were lost during follow-up (34 ? 688 days; mean: 258 days) and 8 patients died within the study period. The duration of functional patency of the treated AVF was 39 ? 660 days (mean: 280 days). Conclusion: Non-maturing or poorly functioning AVF frequently have stenoses in the outflow vein at the original site of surgical vein mobilization. These ?swing point stenoses? are amenable to PTA, which is a safe and effective treatment for prolonging AVF patency and function.
Case reports
Leptospirosis ? 3 cases and a review
Abstract
P. Gerke and L.C. Rump
1Renal Division, University Hospital Freiburg, and
2Marienhospital Herne, Ruhr-University Bochum, Herne, Germany
Leptospirosis is an infectious disease of variable severity characterized by sudden onset of headache, myalgia and prostration. Although most common in the tropics, an increasing number of cases is reported in Europe and Northern America. Severe forms referred to as Weil?s disease commonly involve kidneys, liver, lungs, CNS and heart and require early recognition and immediate initiation of adequate therapy. We describe 3 patients with Weil?s syndrome from an urbanized region in Southern Germany, who developed renal and respiratory failure. PCR facilitated early diagnosis, and therefore, specific treatment before serological tests were positive. Illustrating the case histories, initial presentations and clinical courses, we point out difficulties with early diagnosis and treatment. Furthermore, we offer a comprehensive overview on leptospirosis with emphasis on renal involvement, current diagnostic tools and evidence-based therapy.
Case reports
Macroglobulinemia and membranoproliferative glomerulonephritis in a hepatitis C virus- positive patient
Abstract
Y. Akashi, M. Inoh, N. Gamou, N. Yoshimune, M. Kinashi, S. Ohbayashi and N. Kurata
Department of Internal Medicine, Kinashi Ohbayashi Hospital, Tahamatu City, Kagawa, Japan
A 72-year-old female was admitted to our hospital for massive proteinuria. She had previously been diagnosed with hepatitis C virus (HCV) infection and macroglobulinemia. Renal histological examination demonstrated membranoproliferative glomerulonephritis (MPGN), and type 2 cryoglobulinemia was positive in her serum. It is generally recognized that MPGN is the most common nephritis associated with HCV infection and cryoglobulinemia, but this is the first report of an HCV-infected patient with macroglobulinemia associated with MPGN. After treatment with prednisolone and melphalan, proteinuria disappeared, but macroglobulinemia and cryoglobulinemia were not improved.
Case reports
Transjugular renal biopsy in an unconscious patient maintained on mechanical ventilation
Abstract
R. Sam, S.B. Chebrolu, C.V. Reyes, K.L. Pierce, Z. Molnar, R. Dhand and T.S. Ing
Departments of Medicine, Radiology and Pathology, 1Veterans Affairs Hospital, Hines, 2Stritch School of Medicine, Loyola University Chicago, Maywood, and 3Cook County Hospital, Chicago, Illinois, USA
Aim: Transjugular renal biopsy is a relatively new technique that has often been applied to patients with concomitant renal and liver diseases. It is believed that with this particular biopsy approach, one can avoid the high risk of conventional renal biopsy-related bleeding in patients who also often suffer from coagulopathy. However, other indications for this procedure have not been clearly defined. Herein, we describe an unconscious patient afflicted with acute renal failure and maintained on mechanical ventilation in whom the performance of a renal biopsy was deemed necessary. Methods: The transjugular renal biopsy technique was carried out because this unconscious patient could not follow breathing instructions for a conventional biopsy to be performed. Also, it would have been difficult for the patient to lay prone during the conventional biopsy procedure. Results: A total of 7 glomeruli were obtained and a diagnosis of vasculitis-related necrotizing glomerulonephritis and acute tubular necrosis was made. Subsequently, the patient was treated successfully with steroid therapy. Conclusion: Transjugular kidney biopsy should be considered in unconscious renal biopsy-requiring patients maintained on mechanical ventilation.
Letters to the Editor
An unusual presentation of sarcoidosis
Abstract
P. Carmichael and J.P. O?Donnell
Letters to the Editor
A case of acute renal failure, rhabdomyolysis and disseminated intravascular coagulation associated with scrub typhus
Abstract
S. Lee, K.P. Kang, W. Kim, S.K. Kang, H.B. Lee and S.K. Park
Letters to the Editor
Listeria monocytogenes peritonitis complicated by septic shock in a patient on continuous ambulatory peritoneal dialysis
Abstract
K.C. Tse, F.-K. Li, T.-M. Chan and K.-N. Lai
Letters to the Editor
Changes in individual serum b2-microglobulin in regular hemodialysis
Abstract
T. Yamada and T. Satoh
Letters to the Editor
Fibrates and renal function
Abstract
M. Gajdos and R. Dzúrik
Letters to the Editor
Focal-segmental dense deposit disease with prolonged asymptomatic hematuria
Abstract
J. Soma, K. Sato, T. Sakuma, H. Saito and H. Sato
