Volume 58, No. 6/2002(December)
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 Clinical Nephrology
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Originals
Th1/Th2 balance in childhood idiopathic nephrotic syndrome
Abstract
K. Kaneko, K. Tuchiya, S. Fujinaga, R. Kawamura, Y. Ohtomo, T. Shimizu and Y. Yamashiro
Department of Pediatrics, Juntendo University School of Medicine, Tokyo, Japan
Aims: In view of the conflicting evidence of helper T cell type 1 (Th1) or type 2 (Th2) pattern of cytokine synthesis in childhood idiopathic nephrotic syndrome (INS) this study examined the balance of Th1 and Th2 which are characterized by intracellular cytokine production of interferon-g (IFNg) and interleukin-4 (IL-4), respectively. Subjects and methods: Sixteen children with steroid-sensitive INS (mean age 9.0 years) were included in this study, together with 15 healthy normal children (mean age 7.9 years) for the control group. Intracellular production of both IFNg and IL-4 in helper T cell (CD4+ cell) was investigated by a 3-color flow cytometry. Results: The cross-sectional data showed no significant differences of percentages of Th0 (IFNg+IL-4+ CD4+ cell), Th1 (IFNg+IL-4–CD4+ cell) and Th2 (IFNg–IL-4+ CD4+ cell) in CD4+ cells (p > 0.05). The Th1/Th2 ratio during nephrotic relapse did not differ from those during nephrotic remission and in normal healthy children (p > 0.05). Conclusion: We conclude that there is no significant skew of Th1/Th2 balance in childhood INS and that the cardinal immunological abnormality does not lie in helper T cells but in other cells, such as suppressor/cytotoxic T cells, natural killer cells or monocytes/ macrophage. To clarify the pathogenesis of INS, comprehensive studies for these cells would be worthwhile.
Originals
Color-coded duplex sonography study of arteriovenous fistulae and pseudoaneurysms complicating percutaneous renal allograft biopsy
Abstract
V.M. Brandenburg, R.D. Frank and J. Riehl
Department of Nephrology, University Hospital, RWTH Aachen, Germany
Background: The exact incidence and clinical impact of arteriovenous fistulae (AVF) and pseudoaneurysms as complications emerging from renal allograft biopsy are not well established. We therefore conducted a prospective study using color-coded duplex sonography (CCDS) to determine the frequency, clinical presentation and spontaneous occlusion rate of biopsy-related AVF and pseudoaneurysms in kidney transplant recipients. Methods: We investigated 72 consecutive patients undergoing renal allograft biopsy using an automated biopsy technique. CCDS was performed before, immediately after and up to more than 6 months after biopsy. The diagnosis of AVF was based on the presence of perivascular vibration artifacts and detection of typical Doppler curves. Pseudoaneurysms were diagnosed based on the presence of “to-and-fro” signals. Results: In 5 patients (6.9%), an AVF was detectable before biopsy. Post-biopsy AVF were found in 12 additional patients (16.7%) with a spontaneous occlusion rate of 50% within 48 hours and 75% after 4 weeks. Three (25%) AVF persisted longer than 1 year. Four patients (5.6%) were found to have pseudoaneurysms. All pseudoaneurysms were located closely to AVF and closed spontaneously. None of the post-biopsy AVF and pseudoaneurysms required specific therapy. In 2 patients (2.8%), allograft biopsy lead to significant hemorrhage independent of AVF or pseudoaneurysms. Conclusion: These results indicate that post-biopsy AVF and pseudoaneurysms are a frequent finding after automated renal allograft biopsy. The natural history of these lesions shows a high rate of early occlusion. The present data fail to demonstrate significant clinical impact of AVF and pseudoaneurysms after renal allograft biopsy.
Originals
Doxazosin, but not amlodipine decreases insulin resistance in patients with chronic renal failure: a prospective, randomized-controlled study
Abstract
A. Yildiz1, M. Hursit1, A.V. Çelik1, S.M. Kayacan1, H.Yazici1, V. Akkaya1, A.O. Gürol2 and K. Karsidag2
1Department of Internal Medicine, Division of Nephrology, Istanbul School of Medicine, and 2Department of Diabetology, Institute for Experimental Medical Research, Istanbul, Turkey
Doxazosin and insulin resistance
Insulin resistance (IR) in chronic renal failure (CRF) is well-known. In this randomized-controlled study, we aimed to compare the effect of doxazosin and amlodipine on IR in patients with CRF. Fifteen patients with CRF (male/female: 5/10, mean age: 46 ± 13 years) and 9 controls (male/female: 3/6, mean age: 35 ± 8 years) were included. Patients and controls had no family history of diabetes mellitus. Homeostasis model assessment (HOMA) was calculated as a marker of IR. Patients were grouped randomly to doxazosin (n = 8; 2 – 4 mg/day) and amlodipine (n = 7; 5 – 10 mg/day) arms. Baseline biochemical analysis (fasting serum glucose, BUN, creatinine, uric acid, cholesterol and cholesterol subgroups) and parameters related with insulin metabolism (insulin, C peptide, HOMA) were similar between amlodipine and doxazosin groups. There was no difference in age, gender and body mass index among study groups. The follow-up time was 12 weeks. Patients with CRF had higher HOMA (1.83 ± 0.55 vs 1.00 ± 0.36, p = 0.001), fasting insulin (8.06 ± 1.98 vs 4.46 ± 1.31 IU/l, p < 0.001) and serum triglyceride levels (197 ± 136 vs 112 ± 67 mg/dl, p = 0.04) as compared to controls. Serum HDL cholesterol levels were significantly lower in patients with CRF than controls (40 ± 10 vs 57 ± 14 mg/dl, p = 0.02). HOMA significantly decreased after doxazosin (1.91 ± 0.45 vs 1.41 ± 0.21, p = 0.02), however, no difference was found after amlodipine. Also, fasting insulin levels were decreased after a 12-week doxazosin therapy from 8.17 ± 1.22 vs 6.58 ± 0.84 IU/l, p = 0.02), but no change was seen after amlodipine. Lipid parameters did not significantly change during the study period in 2 groups. No adverse effect requiring drug discontinuation was observed during the 12-week period in the study groups. In conclusion, doxazosin decreases IR in patients with CRF, whereas amlodipine has no effect. This may be of advantage in the treatment of hypertension in this group of patients for preventing some long-term complication of IR.
Originals
b2-microglobulin and hypertensive complications in pregnant women at risk
Abstract
A. Ben-Haroush1, R. Bardin1, A. Erman2, M. Hod1, R.Chen1, B. Kaplan1 and J. Bar1
1Perinatal Division, Department of Obstetrics and Gynecology, and
2Nephrology and Hypertension Institute, Rabin Medical Center, Beilinson Campus, Petah Tiqva and Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel
Background and aim: b2-microglobulin (b2-m) is a polypeptide, which is freely filtered through the glomerular basement membrane and absorbed almost entirely by the proximal tubular cells. Preeclampsia, a common complication of pregnancy, is characterized by pathological renal changes, mainly glomerular lesions. The aim of the present study was to investigate whether serum b2-m measured in the early stages of pregnancy could be used as a marker to predict hypertensive complications in women at increased risk. Patients and methods: Serum b2-m concentrations were prospectively measured in 75 pregnant women with history of chronic hypertension, chronic renal disease, chronic vascular disease or preeclampsia and compared with those in 16 healthy pregnant women. Results: Of the 75 women in the study group, 10 (13%) developed preeclampsia and 20 (26%) had other complications, such as intrauterine growth restriction (n = 8), fetal or neonatal loss (n = 9) and delivery before 30 weeks of gestation (n = 8). Gestational age at delivery, birth weight and cesarean section rate were significantly worse in the patients with complications than in those without and in the healthy controls. No significant difference was detected in early serum b2-m concentrations between the women who later developed preeclampsia or other complications and those who did not. There was a significant positive correlation of b2-m concentrations with serum creatinine level (R2 = 0.394, p < 0.001), but not with gestational week at blood collection. Conclusion: Serum b2-m concentrations are not predictive of the development of preeclampsia or other complications in woman at risk.
Originals
The b2-microglobulin/cystatin C ratio - a potential marker of post-transplant lymphoproliferative disease
Abstract
A. Bökenkamp1, A. Grabensee1, B. Stoffel-Wagner2, C.Hasan1, T. Henne3, G. Offner3 and M.J. Lentze1
1Medical Center of Bonn University, The Children’s Hospital,
2Institute for Clinical Chemistry, Medical Center of Bonn University, Bonn and 3Children’s Hospital, Hanover Medical School, Hanover, Germany
Background: As a consequence of more intensified immunosuppression, post-transplant lymphoproliferative disease (PTLD) is increasingly observed in patients after solid-organ transplantation. b2-microglobulin, a low-molecular weight protein (MW 11.8 kDa), is produced by all nucleated cells as part of the HLA complex. Its serum concentration is directly correlated with prognosis in patients with lymphatic neoplasms. Like other low-molecular weight proteins, b2-microglobulin is eliminated by glomerular filtration. This complicates its use as a tumor marker in renal insufficiency. Cystatin C, a low-molecular weight protein of 13.3 kDa, is a new marker of kidney function largely unaffected by extrarenal disease. We, therefore, sought to assess the potential of the b2-microglobulin/cystatin C ratio (b2M/Cys) as a marker of lymphoproliferation. Patients and methods: b2M/Cys was determined by particle-enhanced immunonephelometry in sera from 132 children with different degrees of renal insufficiency, 5 of whom had lymphoproliferative disease. Renal function was assessed using the Schwartz formula. Results: b2M/Cys was constant between 1.2 and 2.4 mg/mg for Schwartz GFR ³ 40 ml/min×1.73 m2. With lower GFR, b2M/Cys rose progressively, maximum values being found in the hemodialysis patients (4.85 – 11.73). Healthy renal transplant recipients had b2M/Cys comparable to controls. With acute lymphoproliferative disease, all but one patient had significantly elevated b2M/Cys between 2.68 and 3.68 mg/mg, which returned to normal in remission (1.67 – 2.35 mg/mg). The sensitivity of a b2M/Cys ratio > 2.4 mg/mg for the detection of PTLD was 80%, the specificity 100%, positive predictive value 100%, negative predictive value 90%. Conclusion: The b2-microglobulin/cystatin C ratio is a promising parameter of lymphoproliferation in patients with normal or mildly impaired renal function.
Originals
Monocyte apoptosis in dialysis patients is Fas ligand-mediated
Abstract
R. Ranjan, H. Shah, J. Siu, E. Varghese, M. Bhaskaran, K. Reddy, A.A. Kapasi, J.D. Wagner and P.C. Singhal
Departments of Medicine, 1Long Island Jewish Medical Center, and
2North Shore University Hospital, New York, USA
Background: The mononuclear phagocyte system plays an important role in host defense. Since dialysis patients have been reported to show enhanced leukocytes apoptosis, we evaluated the mechanism of increased apoptosis of monocytes in dialysis patients. Methods: Apoptotic studies were carried out on monocytes isolated from dialysis patients as well as healthy subjects. The effect of dialysis sera and membranes was evaluated on monocyte apoptosis as well as monocyte expression of proapoptotic proteins such as Fas and FasL. To confirm the role of FasL, we evaluated the effect of activated secretory products on T cell apoptosis. In addition, we studied FasL content of dialysis sera and supernatants of activated monocytes. Results: Monocytes isolated from dialysis patients (MDP) showed a greater magnitude of apoptosis when compared to monocytes isolated from healthy subjects (MHS) (MHS, 3.6 ± 1.1% vs. MDP, 24.3 ± 1.4%). Sera of hemodialysis patients (SHD) promoted (p < 0.001) apoptosis of MHS when compared to pooled control sera (HPS) (HPS, 0.8 ± 0.5% vs. SHD, 11.5 ± 0.5% apoptotic cells/field). Dialysis membranes, cellulose acetate membranes in particular, promoted monocyte apoptosis. Interestingly, anti-FasL antibodies partly inhibited dialysis sera-induced monocyte apoptosis. Dialysis membranes also modulated monocyte expression of both Fas and FasL. Secretory products of activated monocytes also promoted T cell apoptosis. Dialysis sera and activated monocyte secretory products showed increased FasL content. Conclusions: These results suggest that dialysis patients have an increased rate of monocyte apoptosis, which is mediated through a uremic milieu (serum factors). One of these serum factors seems to be FasL. In addition, dialysis membranes seem to promote apoptosis independent of the uremic milieu. The present study provides a mechanistical insight into the enhanced apoptosis of monocytes in dialysis patients.
Originals
Relationship between body composition, sex hormones
and leptinemia in hemodialyzed patients with chronic renal failure
Abstract
J. Chudek, M. Adamczak, F. Kokot, H. Karkoszka, W. Ignacy, D. Klimek and A. Wiecek
Department of Nephrology, Endocrinology and Metabolic Diseases, Silesian University Medical School, Katowice, Poland
Background: Females are characterized by significantly higher plasma leptin concentration than males. It seems likely that sex hormones influence leptinemia independently from differences in body composition. The aim of the present study was to analyze the contribution of plasma concentrations of testosterone and estradiol on leptinemia in hemodialyzed patients. Methods: 110 hemodialyzed patients – HD (60 M, 50 F) and 70 healthy subjects (HS) (30 M, 40 F) were enrolled in this study. Plasma leptin, testosterone or estradiol and CRP concentrations and body composition by dual-energy X-ray absorptiometry (DEXA) were assessed. Results: Total body fat was significantly higher in females than in males (27.5 ± 1.5% vs. 17.2 ± 1.0% of body weight in HD and 36.0 ± 1.0% vs. 18.2 ± 1.4% in HS, respectively). Plasma leptin concentrations were markedly higher in females than in males both in HD (27.9 ± 5.4 ng/ml vs. 9.6 ± 1.9 ng/ml) and HS (16.5 ± 1.7 ng/ml vs. 3.1 ± 0.4 ng/ml). A highly significant, strong positive correlation was found between total fat mass (TFM) and leptinemia in all studied groups. No significant univaried correlation between plasma leptin and testosterone or estradiol concentrations respectively was found both in HD and HS. Multiple regression analyses showed that the main determinant of leptinemia is TFM (b = 0.623 and 0.798 in HS females and males respectively, and b = 1.058 and 0.797 in HD females and males respectively). Plasma concentration of testosterone (b = –0.139 and b = –0.075 in male HD and HS respectively) and estradiol (b = 0.199 and b = 0.046 in females HD and HS, respectively) contributed to leptinemia only in a minor degree. Conclusion: Both testosterone and estradiol are minor contributors to leptinemia both in HS and HD patients. The main determinant of leptinemia in these subjects is total body fat mass.
Originals
Clinical relevance of hemochromatosis-related HFE C282Y/H63D gene mutations in patients on chronic dialysis
Abstract
C. Canavese, D. Bergamo, S. Barbieri, M. Timbaldi, A. Thea, G. Martina, D. Damiani, R. Fenoglio, B. Donati-Marella and G. Priolo
1Section Nephrology, Departments of Internal Medicine of the University of Torino, Nephrology Units of the 2Martini and 3OIRM-CTO Hospital, and
4Analytical Chemistry Laboratory of the S. Giovanni Molinette Hospital, Torino, Italy
Background: The actual prevalence and the clinical relevance of gene mutations of HFE (which are linked to hemochromatosis) have not yet been established in patients on chronic dialysis. On the basis of theoretical premises, it could be hypothesized that these genetic determinants might influence the response to iron intake and the susceptibility for iron overload in patients in parenteral iron therapy. Furthermore, carriers for these mutations might be prone to develop sporadic porphyria cutanea tarda and cardiovascular events. Methods: C282Y/H63D mutations of HFE gene were evaluated in 132 patients (34 in peritoneal dialysis, 98 in HD) and correlated with biochemical parameters of iron status (ferritin (FER) concentration and transferrin saturation (TSAT)), red cell parameters (red cell size and hemoglobin content), erythropoietin (EPO) dosage, major cardiovascular events and C-reactive protein as marker of chronic inflammation, in patients without iron therapy and after i.v. iron supplementation (£ 60 mg/week) and with the presence of biopsy-proven porphyria. Results: C282Y heterozygous mutation was found in 8/132 (6.6%); H63D homozygous and heterozygous mutations were found in 3/132 (2.3%) and 22/132 (16%) patients, respectively. Two patients (1.5%) showed double heterozygosis. No differences in baseline serum FER and TSAT and the other biochemical and clinical parameters were found in patients bearing mutations alleles nor after continuous iron therapy at low dosages. However, the prevalence of patients capable of maintaining normal hemoglobin (Hb) level without EPO therapy is increased in the C282Y-mutated patients. Only 1 patient out of the 4 with biopsy-proven porphyria cutanea tarda was bearing gene mutations (H63D heterozygosis). Conclusion: C282Y/ H63D HFE gene mutations do not seem to be related to major abnormalities in biochemical parameters of iron status in dialysis patients without iron therapy or after i.v. iron supplementation, granted that low dosages are employed. Obviously, as our patients were exposed to a relatively uniform iron regimen in our clinical center (£ 60 mg/week), it is unclear if other dosing regimens will unmask clinically significant differences between the heterozygotes and normals. The fact that the C282Y-mutated patients more frequently maintain high Hb values without EPO is interesting as could suggest a better use of available iron for erythopoiesis, but needs to be confirmed in larger samples. No clear association is demonstrated with porphyria cutanea tarda and major cardiovascular events.
Originals
Long-term use of 1.1% amino acid dialysis solution in hypoalbuminemic continuous ambulatory peritoneal dialysis patients
Abstract
G.S. Taylor, V. Patel, S. Spencer, R.J. Fluck and C.W. McIntyre
1Renal Dietician, Department of Renal Medicine, Derby City General Hospital, Derby, UK, 2Sister, Peritoneal dialysis Unit, Department of Renal Medicine, Derby City General Hospital, Derby, UK, and 3Consultant Renal Physician, Department of Renal Medicine, Derby City General Hospital, Derby, UK
Introduction: Malnutrition is a common problem in patients treated with continuous ambulatory peritoneal dialysis (CAPD). Hypoalbuminemia in CAPD patients is an independent risk factor for death and is associated with malnutrition. Previous short-term studies have examined the use of amino acid based PD solutions in terms of albumin levels and anthropometric changes, but not clinical outcome. We report on the extended use of 1.1% amino acid based peritoneal dialysis solution (Nutrineal) and have assessed clinical utility in terms of nutrition, biochemical indices, dialysis adequacy and clinical outcomes. Methods: The effect of Nutrineal was studied retrospectively in 22 patients during the past 30 months. All patients had an albumin level of < 35 g/l prior to commencing Nutrineal, and had either a protein intake < 1.2 g/kg or weight loss of > 5% in the previous 3 months. 19 of the 22 patients underwent an 8-week trial of oral nutritional supplements with no improvement in serum albumin level. Albumin level, normalized protein catabolic rate, weight, Kt/V and creatinine clearance were assessed for all patients prior to Nutrineal and at the end of the study period. Results: The mean time on Nutrineal therapy was 13.6 months (range 6 – 26 months). There were no reported side effects of the treatment. There was an average of 1 episode of peritonitis per 23 treatment months, and only 1 patient died (4% annually adjusted mortality cf 8.9% on the peritoneal dialysis program as a whole). There was a significant increase in albumin level from 22.45 ± 0.97 range 14 – 33 g/l to 25.68 ± 1.159 range 16 – 35g/l (p = 0.0036). Normalized protein catabolic rate increased significantly, from 0.898 ± 0.053 to 1.085 ± 0.056 g/kg/day (p = 0.0057). Weight decreased slightly although this did not reach statistical significance. Kt/V and creatinine clearance both decreased significantly, but remained within the adequate range in > 80% of the patients. There was no significant change in residual renal function (mean residual creatinine clearance 3.8 ± 0.59 ml/min at the start of the study period, cf 3.4 ± 0.61 ml/min at the end). Conclusion: These data suggest that Nutrineal can be used safely and effectively for an extended period of time. Such use is associated with a low mortality rate and a low peritonitis rate, although dialysis adequacy is compromised to a degree.
Case reports
Pseudohyperkalemia occurring in a patient with chronic renal failure and polycythemia vera without severe leukocytosis or thrombocytosis
Abstract
H. Fukasawa, R. Furuya, A. Kato, K. Yonemura, Y. Fujigaki, T. Yamamoto and A. Hishida
1First Department of Medicine and 3Hemodialysis Unit, Hamamatsu University School of Medicine, Hamamatsu, and 2Department of Internal Medicine, Iwata City Hospital, Iwata, Japan
Pseudohyperkalemia is defined as a serum potassium concentration 0.4 mEq/l greater than the plasma concentration. The basis of this phenomenon is the release of intracellular potassium from platelets, leukocytes, or erythrocytes, commonly in the setting of extreme leukocytosis (> 10 × 104/ml) or thrombocytosis (> 60 × 104/ml). We report a case of pseudohyperkalemia in a patient with chronic renal failure and polycythemia vera without the finding of severe leukocytosis or thrombocytosis (white blood cell count 1.88 × 104/ml and platelet count 37.9 × 104/ml, respectively). The serum potassium concentration was 8.2 mEq/l, while the plasma potassium level was 6.4 mEq/l in a sample obtained simultaneously. The concentrations of platelet factor IV and b-thromboglobulin, known to be markers of platelet activation, were greater than 100 ng/ml and 200 ng/ml, respectively, indicating that platelet activation may have been related to the development of pseudohyperkalemia in this patient. These findings suggest that pseudohyperkalemia should be considered when hyperkalemia is seen in a patient with chronic renal failure and myeloproliferative disorders.
Case reports
Acute renal failure and hearing loss due to sodium bromate poisoning: a case report and review of the literature
Abstract
H. Sashiyama, Y. Irie, Y. Ohtake, K. Nakajima, H. Yoshida, T. Sakai and K. Okuda
1San-ai Memorial Hospital, and 2Industrial Intoxication Center, Tokyo Rosai Hospital, Tokyo, Japan
Acute renal failure with hearing loss due to sodium bromate intoxication is described. A 48-year-old woman who ingested permanent wave neutralizer in a suicide attempt and developed anuria was admitted to our hospital for hemodialysis. Bromate intoxication was suspected and hemodialysis was carried out; she required maintenance dialysis 3 times a week. Irreversible severe sensorineural hearing loss continued and peripheral polyneuropathy developed in the lower limbs. We measured the concentration of bromine in the serum before and after the first hemodialysis and found its removal rate to be 61.3%. This is the first report that proved the utility of hemodialysis for bromate intoxication in a clinical setting.
Case reports
Benign intracranial hypertension in a patient with chronic renal failure, precipitated by hemodialysis
Abstract
D. Shaw, W. Priestman and C.W. McIntyre
Letter to the Editor
Effects of candesartan and amlodipine on renal function and electrolytes in renal allograft recipients
Abstract
K. Kisters, F. Toknak, M. Kosch, M. Barenbrock and M. Hausberg
