Volume 59, No. 2/2003(February)
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 Clinical Nephrology
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Originals
Insulin resistance highly associates with hypertension in IgA nephropathy
Abstract
M. Eiro, T. Katoh, Y. Sakuma, K. Sakurai, H. Suzuki, K. Asahi, K. Watanabe and T. Watanabe
Departments of Internal Medicine III and Pathology, Fukushima Medical University School of Medicine, Fukushima, Japan
Background: Insulin resistance has been reported to induce hypertension. Previous studies described that there was no relationship between insulin resistance and hypertension in patients with chronic renal diseases with mild to moderate renal dysfunction. The aim of the present study is to clarify the relationship between insulin resistance and blood pressure, renal function, histopathological changes and other characteristics in IgA nephropathy (IgAN). Methods: Eighty-eight IgAN patients were included in this cross-sectional study. Hypertension was diagnosed according to the WHO/ISH criteria. Insulin resistance was evaluated by homeostasis model assessment (HOMA-IR). Results: Male gender, age, body mass index, serum creatinine, urinary protein excretion, triglycerides and HOMA-IR were positively correlated with hypertension. CCr, serum albumin and HDL cholesterol were negatively correlated with blood pressure by Spearman?s simple correlation test. By logistic multivariate analysis, CCr, insulin resistance, age and male gender were significantly correlated with hypertension, independently of all other variables. Conclusions: Insulin resistance is not directly related to renal dysfunction, but is also independently associated with hypertension in IgAN. Since hypertension is considered as a risk factor for renal disease progression, insulin resistance may be an indirect deteriorating factor for IgAN. To identify and improve insulin resistance may be another therapeutic target in the clinical management of IgAN.
Originals
Hospitalized valvular heart disease in patients on renal transplant waiting list: incidence, clinical correlates and outcomes
Abstract
K.C. Abbott, P. Hshieh, D. Cruess, L.Y.C. Agodoa, P.G.Welch, A.J. Taylor and C.M. Yuan
1Nephrology Service, Walter Reed Army Medical Center, Washington, DC, and Uniformed Services University of the Health Sciences, 2Preventive Medicine and Biometrics, Uniformed Services University of the Health Sciences, 3NIDDK, NIH, Bethesda, MD, and 4Cardiology Service, Walter Reed Army Medical Center, Washington, DC, USA
Background: Patients with ESRD are at increased risk for heart valve calcification. It has not been established whether hospitalized valvular heart disease (VHD) is a substantial barrier to renal transplantation (RT) after transplant listing, or whether VHD progresses after RT. Methods: Using data from the USRDS, we studied 35,215 patients with ESRD enrolled on the renal transplant waiting list from July 1994 to June 1997. Cox non-proportional hazards regression models were used to calculate adjusted, time-dependent hazard ratios (HR) for RT and VHD. Results: In comparison to maintenance dialysis (2.2/1,000 person years), RT was independently associated with a lower hazard for hospitalization for VHD (0.7/1,000 person years, HR 0.28, 95% confidence interval 0.17 – 0.47). Renal transplant recipients had much lower rates of VHD after transplant than before (rate ratio (RR) 0.49, 95% CI 0.47 – 0.52). Patients with VHD were significantly less likely to receive RT (adjusted rate for RT 0.38, 95% CI 0.20 – 0.45) but patients who received valve replacement surgeries (VRS) were not affected (adjusted rate for RT 1.10, 95% CI 0.52 – 2.32, not significant). Conclusions: VHD is an uncommon but serious barrier to RT after listing, while VRS is not a significant barrier to RT. Established VHD does not appear to worsen after RT. Clinicians should consider giving increased attention to the detection and treatment of VHD during the pre-transplant evaluation.
Originals
Serum levels of total homocysteine, homocysteine metabolites and of advanced glycation end-products (AGEs) in patients after renal transplantation
Abstract
S. Franke1, A. Müller1, M. Sommer1, M. Busch1, R. Kientsch-Engel2 and G. Stein1
1Department of Internal Medicine IV, University of Jena, and
2Roche Diagnostics GmbH, Penzberg, Germany
Aims: Hyperhomocysteinemia has been described as an independent risk factor for cardiovascular diseases (CVD) influencing patient outcome. Advanced glycation end-products (AGEs) are involved in the pathogenesis of vascular damage in uremia. This study was undertaken to assess whether high serum levels of total homocysteine (tHcy) with its metabolites methylmalonic acid (MMA), methylcitric acid (MCA) and cystathionine (CYSTA) as well as elevated serum concentrations of the AGEs pentosidine and Ne-carboxymethyllysine (CML) are independent risk factors for CVD, left ventricular hypertrophy (LVH) or hypertension as well as kidney dysfunction in renal transplant recipients (RTR). Methods: Serum levels of tHCy, MMA, MCA and CYSTA were measured by a gas chromatographic-mass spectrometric assay, pentosidine by HPLC and CML using an ELISA assay. Results: All measured parameters were significantly higher in RTRs than in healthy subjects (p < 0.0001). The levels of pentosidine and CML as well as of tHcy and its metabolites correlated significantly with each other, but not with those of MMA and CYSTA. Significant correlations were also found between pentosidine and tHcy, MMA or MCA as well as between CML, MMA and MCA, respectively. Acute or chronic rejection did not influence these values. No significant differences were observed between patients with or without CVD or with hypertension. In RTRs with LVH, only the tHcy levels were significantly higher than in those RTRs without LVH (p = 0.006). Logistic regression analysis revealed an independent influence of tHcy on the presence of LVH. Conclusion: These results may indicate an association between high tHcy values and LVH. Further investigation is needed to determine whether a reduction of tHcy and Hcy metabolites and/or AGE serum concentrations would significantly improve patient outcome after undergoing renal transplantation.
Originals
Post-renal transplant syndrome of transient lower limb joint pain: description under a tacrolimus-based immunosuppression
Abstract
E. Goffin, B. Vande Berg, J.-P. Devogelaer, J.-M. Pochet, M. De Meyer, J.-P. Squifflet and Y. Pirson
Departments of 1Nephrology, 2Radiology, 3Rheumatology, 4Renal Transplantation, Cliniques Universitaires St. Luc, Universit
The occurrence of a post-renal transplant syndrome of lower limbs joint pain has been reported extensively over the last decade. Clinical examination of the symptomatic joints is often unremarkable and magnetic resonance imaging reveals abnormalities of the bone marrow suggestive of edema and/or hemorrhage. The main striking features of this syndrome are the spontaneous resolution of the symptoms within a few weeks as well as of the marrow abnormalities. This syndrome has been attributed to cyclosporine, given in the immunosuppression regimen or to epiphyseal impactions. We here document the occurrence of this syndrome in 5 kidney graft recipients given a tacrolimus-based immunosuppression.
Originals
A new system for regional citrate anticoagulation in continuous venovenous hemodialysis (CVVHD)
Abstract
A. Mitchell1, A.E. Daul1, M. Beiderlinden2, R.F. Schäfers1, U. Heemann1, A. Kribben1, J. Peters2, T. Philipp1 and R.R. Wenzel1
1Division of Nephrology and Hypertension, Department of Internal Medicine, and 2Department of Anesthesiology and Intensive Care Medicine, University Hospital, Essen, Germany
Background: CVVHD is an established renal replacement therapy in hemodynamically unstable ICU patients. Various methods for regional citrate anticoagulation have been developed to minimize bleeding complications. Metabolic alkalosis, the risk of severe hypocalcemia and need for continuous calcium substitution as well as treatment-associated hypernatremia have limited the success of systems employed so far. We have developed a new technique for regional citrate anticoagulation in CVVHD to overcome these deficiencies and have performed a validation study. Methods: One hundred and thirty-three filters with an overall treatment duration of 3,324 hours were used in 19 critically ill patients with bleeding complications. We used a calcium-containing dialysate (1.81 mmol/l Ca) to avoid mandatory systemic calcium supplementation. Sodium bicarbonate was added to the dialysate in variable concentrations (13 – 34 mmol/l) to control acid-base status and prevent hypernatremia. The resulting dialysate sodium concentrations were between 121 and 140 mmol/l. Blood flow was set at 75 ml /min. Infusion of a solution containing trisodium citrate and citric acid with an overall citrate concentration of 113 mmol/l was started at 250 ml/h. Primary endpoints were pre- and post-filter ionized calcium (Cai) concentrations, base excess and serum sodium. Filter life was assessed as a secondary end-point. Results: Control of electrolyte balance and azotemia was excellent (pre-filter serum Cai 1.06 ± 0.012 mmol/l (± SEM), post-filter Cai 0.23 ± 0.01 mmol/l, base excess –0.39 ± 0.4 mmol/l, serum sodium 137 ± 4 mmol/l, mean serum creatinine 1.8 ± 0.07 mg/dl). Normal base excess was achieved with a mean dialysate bicarbonate concentration of 26 mmol/l at a mean citrate infusion rate of 266 ± 4 ml/h. After 48 hours, 25% of filters were still patent, mean filter life was 26 ± 1.6 hours. No patient developed serious CVVHD-related adverse events. Conclusion: The new regional citrate anticoagulation system for CVVHD is safe, feasible and can avoid major complications of previously described methods, especially hypocalcemia, alkalosis and hypernatremia.
Originals
Content of reticulocyte hemoglobin is a reliable tool for determining iron deficiency in dialysis patients
Abstract
K. Tsuchiya, H. Okano, M. Teramura, Y. Iwamoto, N.Yamashita, A. Suda, K, Shimada, H. Nihei and M. Ando
1Department of Medicine IV, 2Department of Clinical Laboratory, Tokyo Women’s Medical University, 3Yoyogi Yamashita Clinic, 4Suda Clinic, 5Department of Biostatistics, STATZ Corporation, and 6Division of Nephrology, Tokyo Metropolitan Geriatric Hospital, Tokyo, Japan
Background: The evaluation of iron status in dialysis patients provides information essential to the planning of adequate recombinant human erythropoietin (rHuEPO) treatment. Iron status of the patients can be determined from the recently available measurement of content of reticulocyte hemoglobin (CHr). Methods: In this study, to clarify the accuracy of CHr in diagnosing iron deficiency in hemodialysis (HD) patients, we initially compared CHr with such conventional iron parameters as serum ferritin levels, transferrin saturation and serum soluble transferrin receptor levels. Secondly, we investigated the changes in CHr during iron supplementation for iron-deficient patients to determine whether this marker is a prospective and reliable indicator of iron sufficiency. The participants in this study were 149 hemodialysis (HD) patients and 53 age-matched healthy subjects. Iron deficiency was defined as having a TSAT of less than 20% and serum ferritin of less than 100 ng/ml. Conventional parameters of red blood cells and CHr were measured by an ADVIA120 autoanalyzer. Results: Mean CHr was 32.3 ± 2.2 pg in the patients undergoing hemodialysis treatment. CHr significantly correlated with iron parameters in the dialysis patients. Logistic regression analysis was performed to determine the relationship between CHr and each outcome measure, and CHr was the significant multivariate predictor of iron deficiency. Iron supplements given to the patients with low CHr and hematocrit (Hct) significantly increased Hct, resulting in a decrease in the weekly dosage of rHuEPO. Conclusions: CHr, measured simultaneously with Hct, is a sensitive and specific marker of iron status in dialysis patients.
Originals
Plasma serotonin and histamine levels in hemodialysis-related pruritus are not significantly influenced by 5-HT3 receptor blocker and antihistaminic therapy
Abstract
E. Weisshaar1, N. Dunker1, U. Domröse2, K.H. Neumann2 and H. Gollnick1
Departments of 1Dermatology, Venereology and 2Nephrology, Otto von Guericke University, Magdeburg, Germany
Background: Elevated plasma histamine levels are considered to play a part in the pathophysiology of hemodialysis-related pruritus. However, antihistaminic therapy often fails to provide sufficient relief. Elevated serotonin levels in patients on dialysis therapy have also been described but the effects of 5-HT3 receptor antagonists on hemodialysis-related pruritus remain controversial. Methods: we conducted a study to determine plasma histamine and serotonin levels before and after treatment with 5-HT3 receptor antagonists (tropisetron 5 mg and ondansetron 8 mg) and an antihistamine (cetirizine 10 mg). Eleven hemodialysis patients with a history of pruritus participated in this study, 10 healthy volunteers served as control group. Results: Histamine and serotonin values were normal in patients and controls. Treatment with cetirizine did not significantly reduce histamine levels in patients or in controls. Tropisetron and ondansetron likewise did not alter serotonin levels in patients. Tropisetron treatment did not significantly change serotonin levels in controls. Conclusion: Histamine and serotonin are no major mediators of pruritus in hemodialysis patients. Elevated histamine levels are occassionally seen and may be due to the increased mast cell number found in a subgroup of hemodialysis patients. Our findings explain the only marginal relief of antihistamines and the controversial antipruritic effect of serotonin receptor antagonists in hemodialysis-elated pruritus.
Originals
Increasing blood flow increases Kt/Vurea and potassium removal but fails to improve phosphate removal
Abstract
J.-P. Gutzwiller, D. Schneditz, A.R. Huber, C. Schindler, E. Garbani and C.E. Zehnder
1Division of Nephrology, Kantonsspital Liestal, University of Basle, Switzerland, 2Department of Physiology, Karl Franzens University of Graz, Austria, 3Central Laboratory, Kantonsspital Aarau, Switzerland, 4Institute for Social- and Preventive Medicine, University of Basle, Switzerland, and 5Clinica Las Condes, Santiago, Chile
Background: Hyperphosphatemia and hyperkalemia are major determinants of morbidity and mortality in hemodialysis patients. Half of the dialysis population suffers from hyperphosphatemia which is now recognized as an important cardiovascular disease risk factor. It is, therefore, necessary to improve the removal of these molecules. In this study, we investigated the effect of enhancing blood flow on Kt/V for urea (Kt/Vu), potassium and phosphate removal. Methods: Thirteen patients were investigated in a randomized, cross-over, prospective study using 3 blood flows (Qb) of 200, 250 and 300 ml/min which gave 39 standardized high-flux hemodialysis treatments. Effective blood flows were measured by ultrasonic flow meter. Quantification of delivered dialysis dose was performed by partial dialysate and ultrafiltrate collection for the determination of potassium and phosphate removal and by blood urea concentrations for determination of Kt/Vu. Results: Kt/Vu rose significantly from 1.10 ± 0.14 to 1.22 ± 0.14 and finally to 1.39 ± 0.16 (p = 0.0001) with increasing Qb similar to the increase in potassium removal from 53.0 ± 2.4 to 63.4 ± 2.6 and to 74.2 ± 3.8 mMol (p = 0.01). Phosphate removal only improved from 28.1 ± 1.3 to 31.4 ± 1.5 (p = 0.050) when Qb was increased from 200 to 250 ml/min but remained unchanged at 31.2 ± 1.5 mMol (NS compared to phosphate removal at Qb = 250 ml/min) when Qb was increased to 300 ml/min. Conclusions: Increasing delivered Kt/Vu and potassium removal with higher Qb fails to produce the same desired effect with phosphate removal during high-flux hemodialysis.
Case reports
Membranous glomerulopathy and acute interstitial nephritis following treatment with celecoxib
Abstract
G.S. Markowitz1, D.C. Falkowitz2, R. Isom3, M. Zaki4, S. Imaizumi5, G.B. Appel3 and V.D. D’Agati1
1Department of Pathology, Columbia University, College of Physicians and Surgeons, New York, NY, 2Department of Medicine, Hahnemann University Hospital, Philadelphia, PA, 3Department of Medicine, Columbia University, College of Physicians and Surgeons, New York, NY, 4Department of Medicine, Community Medical Center, Toms River, NJ, and 5Department of Pathology, Lankenau Hospital, Wynnewood, PA, USA
Both membranous glomerulopathy and acute interstitial nephritis have been reported to occur following treatment with non-steroidal anti-inflammatory drugs. We report the first cases of membranous glomerulopathy and acute interstitial nephritis following treatment with celecoxib (Celebrex), a selective COX-2 inhibitor. The rapid and complete resolution of both conditions following discontinuation of Celebrex strongly implicates this agent in disease pathogenesis. These cases enlarge the spectrum of potential renal toxicities of the COX-2-specific non-steroidal anti-inflammatory drugs.
Case reports
WT-1 and NPHS2 mutation analysis in patients with non-familial steroid-resistant focal-segmental glomerulosclerosis
Abstract
M.M. Löwik, E.N. Levtchenko, L.A.H. Monnens and L.P.W.J. van den Heuvel
University Medical Center Nijmegen, Department of Pediatrics, Nijmegen, The Netherlands
Background: Familial forms of steroid-resistant nephrotic syndrome with the histologic findings of focal-segmental glomerulosclerosis have frequently a genetic basis. For the non-familial forms this is still unresolved. Patients and methods: Ten children with non-familial steroid-resistant nephrotic syndrome along with focal-segmental glomerulosclerosis were tested for mutations in the WT-1 and NPHS2 genes. Results: In 1 patient, a mutation in intron 9 of the WT-1 gene and in 1 patient a heterozygous NPHS2 mutation could be detected. Both abnormalities are important for the treatment modalities and prognosis. Conclusion: Additional studies will have to provide a solid basis for the recommendation of mutation analysis in non-familial steroid-resistant focal-segmental glomerulosclerosis.
Letters to the Editor
Evolution of bone stiffness
in renal transplant patients measured by quantitative ultrasound
Abstract
M. Kosch, K. Kisters and M. Hausberg
Letters to the Editor
A case of early onset cyclosporine-induced hemolytic uremic syndrome resulting in renal graft loss
Abstract
W. Kim, B.J. La, S. Lee, H.C. Yu, B.H. Cho, M.J. Kang and S.K. Park
Letters to the Editor
Fluctuating levels of anti-GBM antibodies following a fungal infection in a patient with secondary amyloidosis
Abstract
G.C. Tsagalis, V. Margelos, N. Nikolopoulou and V.E. Hadjiconstantinou
