Volume 67, No. 6/2007(June)
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 Clinical Nephrology
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Review
De novo thrombotic microangiopathy. An underrated complication of renal transplantation
Abstract
C. Ponticelli
Instituto Auxologico Italiano, Milano, Italy
After kidney transplantation thrombotic microangiopathy (TMA) may recur in patients with previous hemolytic uremic syndrome or may develop de novo. De novo TMA has been reported to occur in less than 1% of renal transplant recipients by large registries, but single center series reported an incidence of the disease as high as 14 � 20%. A number of factors may predispose to posttransplant TMA, including ischemia-reperfusion injury, acute rejection, viral infection. Immunosuppressive treatment can also contribute to the development of de novo TMA. Calcineurin inhibitors may cause or aggravate endothelial lesions through their pronecrotic, vasoactive and profibrotic activity. Anti-mTOR agents may delay the repair of the endothelial damage through their interference with endothelial growth factor. Usually, TMA develops in the early posttransplant period but may also occur later. Clinically, TMA is characterized by progressive renal failure and hypertension. Microangiopathic hemolytic anemia and thrombocytopenia may occur in about 60% of cases. Histologically, TMA may be localized to glomeruli or may involve arteries or both. The prognosis depends on the timely diagnosis and on histological picture. Treatment is based on the removal of inciting factors. Early plasmapheresis could improve clinical signs and symptoms and rescue renal function in a number of patients. Anecdotal successes have also been reported with intravenous immunoglobulins and rituximab.Correspondence to:
Prof. C. Ponticelli Via Ampere 126 20131 Milano, Italy
Email: claudio.ponticelli@fastwebnet.it
Originals
Beneficial effect of low-density lipoprotein apheresis (LDL-A) on refractory nephrotic syndrome (NS) due to focal glomerulosclerois (FGS)
Abstract
E. Muso, M. Mune, N. Yorioka, Y. Nishizawa, T. Hirano, M. Hattori, S. Sugiyama, T. Watanabe, K. Kimura, H. Yokoyama, H. Sato and T. Saito
1Department of Nephrology and Dialysis, The Tazuke Kofukai Medical Research institute Kitano Hospital, Osaka, 2Department of Clinical Nutrition, Graduate School of Human Health Science, Siebold University of Nagasaki, Nagasaki, 3Department of Advanced Nephrology, Graduate School Biomedical Sciences,, Hiroshima University, Hiroshima, 4Department of Metabolism, Endocrinology and Molecular Medicine, Osaka City University Graduate School of Medicine, Osaka, 5First Department of Internal Medicine, Showa University School of Medicine, Tokyo, 6Department of Pediatric Nephrology, Kidney Center, Tokyo Women�s Medical University, School of Medicine, Tokyo, 7Division of Nephrology, Department of Internal Medicine, Fujita Health University School of Medicine, Aichi, 8Department of Internal Medicine III, Fukushima Medical University School of Medicine, Fukushima, 9Department of Internal Medicine, Division of Gastroenterology and Hepatology, St. Marianna University School of Medicine, Kanagawa, 10Department of Gastroenterology and Nephrology, Division of Blood Purification, Graduate School of Medical Science, Kanazawa University, Kanazawa, 11Department of Nephrology, Endocrinology and Hypertension, Tohoku University Hospital, Miyagi, 12Division of Nephrology and Rheumatology, Department of Internal Medicine, Fukuoka University School of Medicine, Fukuoka, Japan
Aims: Hypercholesterolemia is one of the factors which deteriorate renal function in NS especially due to FGS. LDL-A is a potential option for treating NS due to FGS accompanied by hypercholesterolemia and resistant to conventional drug therapy with steroids and/or cyclosporine A (CsA). As reported by Muso et al. [2001], LDL-A combined with drug therapy yields more rapid relief from NS and better prognosis than drug therapy alone. However, very limited data are available on outcome at several years after treatment. The aim of this study was to clarify long-term outcome of NS patients treated with LDL-A and to evaluate the effectiveness of this treatment. Patients and methods: To clarify the long-term outcome of LDL-A, we conducted a retrospective survey on outcome up to 5 years. From 36 hospitals in Japan, 41 patients with NS whose short-term outcomes with LDL-A were reported from 1999 � 2004 were collected and analyzed. Results: In all, 29 and 15 patients with outcomes determined at 2 and 5 years after treatment, respectively, were obtained. At 2 and 5 years after treatment, 62 and 87% of patients, respectively, were classified into complete or Type 1 incomplete remission. The strength of correlations between outcome and several factors including parameters of renal function measured before and after treatment and treatment condition revealed that early administration of LDL-A after the onset of NS provided a good long-term outcome. The data also suggest that more drastic decrease of LDL favored a better prognosis. Conclusions: In NS due to FGS treated with LDL-A, long-term outcome was as good as short-term outcome. Early administration of LDL-A after the onset of NS provided a good long-term outcome. To obtain more precise findings regarding the effects of this treatment, a large-scale prospective study will be needed.Correspondence to:
Dr. E. Muso Department of Medicine Division of Nephrology and Dialysis Kitano Hospital The Tazuke Kofukai Medical Research Institute Osaka, Japan
Email: muso@kitano-hp.or.jp
Originals
Centropontine myelinolysis after correction of hyponatremia: role of associated hypokalemia
Abstract
A.E. Heng, P. Vacher, B. Aublet-Cuvelier, J.M. Garcier, V. Sapin, P. Deteix and B. Souweine
1Service de Néphrologie et Réanimation Médicale, Hôpital G. Montpied, 2Service d’Épidémiologie Médicale, 3Service d’Imagerie Médicale, CHU Clermont-Ferrand, 4Laboratoire de Biochimie, Hôpital G. Montpied, 5Faculté de Médecine, Université Clermont 1, Clermont-Ferrand, France
1Service de Néphrologie et Réanimation Médicale, Hôpital G. Montpied, 2Service d’Épidémiologie Médicale, 3Service d’Imagerie Médicale, CHU Clermont-Ferrand, 4Laboratoire de Biochimie, Hôpital G. Montpied, 5Faculté de Médecine, Université Clermont 1, Clermont-Ferrand, FranceCorrespondence to:
A.-E. Heng, MD CHU Clermont-Ferrand Service de Néphrologie Réanimation Médicale Hôpital Gabriel Montpied BP 69, 63003 Clermont Ferrand Cedex 1, France
Email: aheng@chu-clermontferrand.fr
Originals
C-reactive protein and low albumin are predictors of morbidity and cardiovascular events in chronic kidney disease (CKD) 3-5 patients
Abstract
S. Soriano, L. González, A. Martín-Malo, M. Rodríguez and P. Aljama
1Service of Nephrology and 2Unit of Investigation, University Hospital Reina Sofía, Córdoba, Spain
Background: Overall and cardiovascular mortality are significantly higher in hemodialysis patients with elevated C-reactive protein (CRP). The aim of this study was to determine whether CRP is a marker of overall and cardiovascular morbidity in chronic kidney disease (CKD) 3-5 patients. Methods: 90 chronic kidney disease 3-5 patients were prospectively followed during a period of 24 months. Cardiovascular events were defined as episodes of myocardial infarction, stroke, angina pectoris and/or peripheral vascular disease. Morbidity was analyzed in terms of both the need for hospital admission (> 48 h) and total number of days of hospitalization during the follow-up period. CRP was stratified into tertiles of low (< 8 mg/l), medium (8 – 10.5 mg/l) and high (> 10.5 mg/l). The use of some drugs such as ACE inhibitor and ARAII were also recorded. Results: During the follow-up period, 23 patients (25%) required hospital admission. New cardiovascular events were observed in 20 patients (22%), 10 patients died during the follow-up. Adjusted Cox regression analysis revealed that CRP and serum albumin significantly predicted the risk of cardiovascular events. Similarly, high CRP, low serum albumin and low hemoglobin levels predicted morbidity as measured by the number of hospitalizations. Hemoglobin and albumin levels were lower in patients with high CRP (>= 10.5 mg/l, highest tertile) as compared with low CRP levels (<= 8 mg/l, lowest tertile). Patients receiving treatment with angiotensin-converting enzyme (ACE) inhibitors or angiotensin II receptor Type 1 antagonist (ARA-II) had significantly lower levels of CRP than those who were not under such treatment (n = 46, CRP = 8.7 (5.1 – 29.8) vs n = 44, CRP = 10.4 (6.1 – 37.2), p < 0.05) (Figure 1). Conclusions: Our results show that CRP and low albumin, markers of inflammation, predict cardiovascular events and morbidity in CKD 3-5 patients before initiation of chronic hemodialysis.Correspondence to:
S.S. Cabrera, MD Servicio de Nefrología Hospital Universitario Reina Sofía Avda Menéndez Pidal s/n 14004 Córdoba, Spain
Email: marias.soriano.sspa@juntadeandalucia.es
Originals
Human serum paraoxonase concentration predicts cardiovascular mortality in hemodialysis patients
Abstract
Y. Ikeda, T. Suehiro, T. Itahara, Y. Inui, H. Chikazawa, M. Inoue, K. Arii and K. Hashimoto
1Department of Endocrinology, Metabolism and Nephrology, Kochi Medical School, Kochi University, 2Department of Internal Medicine, Tosa Municipal Hospital, 3Department of Internal Medicine, Kohoku Municipal Hospital, 4Department of Internal Medicine, Kubokawa Hospital, Kochi, Japan
Aims: Human serum paraoxonase (PON1) is associated with high-density lipoprotein, and inhibits oxidative modification of low-density lipoprotein. Therefore, PON1 is supposed to contribute to the prevention of atherosclerosis. We and other investigators have shown that the enzymatic activities and concentrations of PON1 were decreased in maintenance hemodialysis (HD) patients. However, the effect of PON1 status on the long-term outcome of HD patients has not been reported. In this study, we examined the association between baseline PON1 status and cardiovascular mortality in an observation study of an outpatient HD population. Patients and methods: The relation between baseline cardiovascular risk factors and clinical events was investigated, during 6 years of follow-up, in 81 HD patients (50 males and 31 females) whose enzymatic activities, concentrations and genetic polymorphisms of PON1 had been determined in a previous study. Results: During follow-up for 6 years, we recorded 42 deaths, including 24 fatal cardiovascular events. In univariate analyses, baseline PON1 concentration was associated with not only cardiovascular mortality (p < 0.005), but also all-cause mortality (p < 0.001) during the period of follow-up, as were age, preexisting cardiovascular disease (CVD) and hemoglobin concentration. In a multivariate Cox regression analysis, PON1 concentration retained significant associations with cardiovascular mortality (p < 0.05) and all-cause mortality (p < 0.005) even after correction of known risk factors for CVD or mortality in HD patients. Using Kaplan-Meier survival curves, we assessed the association between low and high concentrations of PON1 divided according to the median value (7.52 U/ml). Significantly increased cardiovascular mortality (log rank 6.125, p = 0.01) and all-cause mortality (log rank 7.113, p < 0.01) were detected in the patients with low PON1 concentrations. Conclusions: These data suggest that low PON1 concentration may be an independent predictor of cardiovascular mortality in maintenance HD patients.Correspondence to:
Y. Ikeda, MD, PhD Department of Endocrinology Metabolism and Nephrology Kochi Medical School Kochi University Kohasu, Okoh-cho, Nankoku, Kochi, 783-8505, Japan
Email: ikeday@kochi-u.ac.jp
Originals
Anemia associated with pegylated interferon-α2a and α2b therapy in hemodialysis patients
Abstract
M. Espinosa, M.D. Arenas, M.D. Aumente, G. Barril, J.M. Buades, B. Aviles, D. Carretero, M.A. Alvarez-Lara, F. Carnicer, A.M. Malo and P. Aljama
1Servicio de Nefrología, Hospital Universitario Reina Sofía, Cordoba, 2Servicio de Nefrologia, Hospital Perpetuo Socorro, Alicante, 3Servicio de Farmacia, Hospital Universitario Reina Sofia, Cordoba, 4Servicio de Nefrología, Hospital de la Princesa, Madrid, 5Servicio de Nefrologia, Hospital Son Llatzer, Palma de Mallorca, 6Servicio de Nefrologia, Hospital Costa del Sol, Marbella, 7Centro de Hemodiálisis, SOCODI, Cordoba and 8Servicio de Digestivo, Hospital General de Alicante, Spain
Aims: Anemia is a well-known side effect of interferon therapy since interferons are potent inhibitors of erythropoiesis. The aim of this study was to compare the anemia associated with pegylated interferon (PEG-IFN) α2a versus α2b therapy in hemodialysis patients (HD) with chronic hepatitis C. Methods: In order to study the anemia, doses of erythropoietic growth factors (EGF), hemoglobin (Hb) and erythropoietin resistance index (ERI) were compared at baseline and after PEG-IFN-α2a or α2b therapy in 16 HD patients with chronic C hepatitis. Pharmacokinetic studies were performed in 4 of those treated with PEG-IFN-α2b and 2 patients treated with PEG-IFN-α2a. Secondary end-points were viral response and serious adverse events. Results: At 4 – 6 months after the beginning of therapy, both PEG-IFN-α induced a significant increment in the erythropoietin resistance index. This increment was significantly higher in patients treated with PEG-IFN-α2a when compared with α2b (45 vs 9.9, p = 0.012). The pharmacokinetics of PEG-IFN-α2a and α2b in HD patients were different, the Cmax, Cmin and the area under the serum concentration time curve, were all higher in patients treated with PEG-IFN-α2a compared with PEG-INF-α2b. Discontinuation of therapy occurred in 2 (28.5%) of the 7 patients in the PEG-IFN-α2a group and in 4 (44%) of the 9 patients in the PEG-IFN-α2b group. Three (42%) subjects in the α2a group and 5 (55%) in the α2b group had a response at the end of the 48 weeks of therapy. In 4 (44.4%) of the 9 patients treated with α2b the viral response was sustained. Conclusions: In summary, patients treated with PEG-IFN-α2a have a major inhibitory effect on erythropoiesis. This could be explained by the different pharmacokinetic properties of PEG-IFN-α2a and α2b. Further studies are needed to clarify how these findings influence the efficacy, safety and cost-effectiveness of the PEG-IFN-α2.Correspondence to:
Dr. M. Espinosa Servicio de Nefrología Hospital Universitario Reina Sofia Avda. Menéndez Pidal s/n Cordoba 14004,Spain
Email: espinosahe@supercable.es
Originals
Six-year follow-up of azathioprine and mycophenolate mofetil use during the first 6 months of renal transplantation
Abstract
S.J. Rippin, A.L. Serra, H.-P. Marti and R.P. Wüthrich
Clinic for Nephrology, University Hospital, Zürich, Switzerland
Long-term follow-up examination to test whether therapy with mycophenolate mofetil (MMF) or azathioprine (AZA) during the first year translates into different graft or patient survival and graft function is important. Therefore, 6-year follow-up data of a group of 80 consecutive renal transplant recipients were analyzed. The first group of 40 patients was treated with AZA, cyclosporine and prednisone and the second group with MMF, cyclosporine and prednisone for the first 6 months. Graft failure rates were compared during follow-up. Creatinine, inverse slope of creatinine (delta/creatinine) and 24-hour proteinuria at 6 years post transplantation were compared. The Kaplan-Meier analyses for death-censored and non-censored graft failure showed no difference between the groups. Creatinine values at 6 years for the AZA Group were 139 ± 36 µmol/l (95% CI 125.9 – 151.2 µmol/l) and for the MMF Group 149 ± 52 µmol/l (95% CI 133.9 – 164.9 µmol/l). Delta/creatinine and 24-hour proteinuria at 6 years did not differ between the two groups. We conclude that an initial 6-month treatment with MMF as opposed to AZA reduced the early rejection rate, but did not result in superior long-term graft function or survival after 6 years of follow-up observation.Correspondence to:
Prof. R.P. Wüthrich Clinic for Nephrology University Hospital Rämistraße 100 8091 Zürich, Switzerland
Email: rudolf.wuethrich@usz.ch
Originals
Plasma adiponectin concentration in patients after successful kidney transplantation – a single-center, observational study
Abstract
M. Adamczak, M. Szotowska, J. Chudek, H. Karkoszka, L. Cierpka and A. Wieçek
1Department of Nephrology, Endocrinology and Metabolic Diseases, 2Department of General, Vascular and Transplant Surgery, Medical University of Silesia, Katowice, Poland
Background and aim: Adiponectin is an anti-inflammatory protein secreted almost exclusively by adipocytes which improves insulin sensitivity and presents antiatherogenic properties. Plasma adiponectin concentration is almost 3 times higher in hemodialysis patients and markedly decreased after successful kidney transplantation. However, until now, there are no studies analyzing plasma adiponectin concentration in kidney transplant patients (KTx) during the long-term period after transplantation. Therefore, the aim of present study was to examine plasma adiponectin concentration in KTx patients during the wide range of time after transplantation. Material and method: Single center, cross-sectional study including 228 KTx adult recipients (143 M and 85 F) with estimated glomerular filtration rate (eGFR) >= 15 ml/min, 80 hemodialysis patients (34 M and 46 F) and 52 healthy subjects (33 M and 19 F). Plasma adiponectin concentration was estimated together with HOMA-IR (homeostasis model assessment insulin resistance index) and plasma lipid profile. Results: In KTx patients plasma adiponectin concentration 14.0 (13.1 – 15.0) µg/ml was significantly (p < 0.001), lower than in hemodialysis ones 29.0 (24.7 – 33.3) µg/ml, however, significantly (p < 0.001) higher than in healthy subjects 10.1 (8.8 – 11.5) µg/ml. Among KTx patients the highest plasma adiponectin concentration was observed in the subgroup of patients surviving with the functioning graft more than 8 years after transplantation. In KTx patients, significant, negative correlations were found between plasma adiponectin concentration and BMI (p = 0.017), HOMA-IR (p = 0.02) and estimated GFR (p < 0.009), respectively. Multiple regression analysis performed in the group of KTx patients, with plasma adiponectin concentration as the dependent variable and BMI, age, gender, estimated GFR as independent variables showed that in this model (R2 = 0.09) plasma adiponectin concentration significantly depends on BMI (p = 0.035), gender (p = 0.004) and eGFR (p = 0.023). Conclusions: Patients with long-term renal graft survival are characterized by a higher plasma adiponectin concentration. Kidney graft function (assessed as estimated GFR) is an important factor influencing plasma adiponectin concentration.
Correspondence to:
Prof. Dr. Hab. A. Wieçek, FRCP (Edin.) Department of Nephrology, Endocrinology and Metabolic Diseases Medical University of Silesia Francuska 20/24 Str. 40-027 Katowice, Poland
Email: awiecek@spskm.katowice.pl
Case Reports
Treatment of severe hypothyroidism in a patient with progressive renal failure leads to significant improvement of renal function
Abstract
M.E. van Welsem and S. Lobatto
Department of Internal Medicine, Tergooiziekenhuizen Hilversum, Hilversum, The Netherlands
The case of a 41-year-old patient with end-stage renal failure and diabetes mellitus Type 1 who was being prepared for renal replacement therapy is described. After severe hypothyroidism was diagnosed, thyroid hormone substitution therapy was started. Subsequently, a substantial decline in serum creatinine was observed. Creatinine clearance rose from 19 to 40 ml/min and renal replacement therapy was no longer imminent. Several studies have described the pathophysiology of diminished renal function in hypothyroidism. Few studies or case reports have shown amelioration of end-stage renal failure as seen in our patient. The etiology is presumed to be multifactorial, in which hemodynamic effects and a direct effect of thyroid hormone on the kidney play an important role. Diagnosing signs of hypothyroidism and therapy with thyroid hormone in progressive renal failure could be very important in delaying the need for renal replacement therapy.Correspondence to:
Dr. S. Lobatto Department of Internal Medicine Tergooiziekenhuizen Hilversum Postbus 10016 1201 DA Hilversum, The Netherlands
Email: slobatto@zhh.nl
Case Reports
Acute renal failure due to mantle cell lymphoma – a case report and discussion of the literature
Abstract
J. Davies, D.A. Healey, K.M. Wood, K. Jones and N.S. Kanagasundaram
1Department of Infectious Diseases and Tropical Medicine, Royal Liverpool and Broadgreen University Hospital, Liverpool, 2Department of Nephrology, 3Department of Pathology, Freeman Hospital, Newcastle-upon-Tyne, UK
Acute renal failure secondary to lymphomatous infiltration of the kidneys is a rare manifestation raer mantle cell lymphoma (MCL). We present the case of a 76-year-old gentleman with acute renal failure an a background of previously treated low grade non-hodgkin lymphoma. At the time of presentation he complained only of mild lethargy und had no lymphadenopathy or organomegaly. Renal ultrasound revealed bilaterally enlarged kidneys and renal biopsy confirmed MCL. Mantle cell lymphoma runs an aggressive course and accurate diagnosis is very important in guiding appropriate treatment. This case demonstrates the importance of renal biopsy in the diagnosis of renal lymphomatous infiltration but also highlights the potential utility of histological examination in guiding targeted therapy.Correspondence to:
Dr. J. Davies Department of Infectious Diseases and Tropical Medicine Royal Liverpool and Broadgreen University Hospital Prescott Street Liverpool L7 8XP, UK
Email: rafikijaneuk@yahoo.co.uk
Case Reports
Two cases of calciphylaxis treated by parathyroidectomy: importance of increased bone formation
Abstract
H. Maeda, M. Tokumoto, H. Yotsueda, M. Taniguchi, K. Tsuruya, H. Hirakata and M. Iida
1Department of Medicine and Clinical Science, 2Department of Integrated Therapy for Chronic Kidney Disease, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan
Calciphylaxis (calcific uremic arteriolopathy) is a poorly understood and highly morbid syndrome of both vascular calcification and skin necrosis. The main histopathological finding is calcium deposits within arteriolar and small vessel walls, showing endovascular fibrosis associated with fat necrosis. The therapeutic strategy is to normalize the high calcium-phosphate products (Ca × P). When calciphylaxis is complicated with advanced renal hyperparathyroidism (HPT), parathyroidectomy (PTX) should be performed promptly. However, for patients with low PTH level, calciphylaxis is unresponsive to PTX, and such an approach may worsen hyperphosphatemia and hypercalcemia. We report two patients with calciphylaxis confirmed by skin biopsy. PTX was performed in both patients based on high PTH levels. PTH and Ca × P level decreased in both patients post PTX. In Case 1, the skin ulcers gradually improved and almost disappeared after PTX. However, in Case 2, new ulcers appeared after PTX. In Case 1, alkaline phosphatase (ALP) after PTX was approximately twice its level before surgery and PTX resulted in normalization of uptake on bone scintigraphy. However, no rise in ALP was noted in Case 2, probably due to long-term use of aluminum, which prevented bone formation. These findings suggest that differences in the extent of bone formation explain the different response in post-PTX ulcer healing.Correspondence to:
K. Tsuruya, MD, PhD Department of Integrated Therapy of Chronic Kidney Disease Graduate School for Medical Sciences Kyushu University Maidashi 3-1-1, Higashi-ku, Fukuoka 812-8582, Japan
Email: tsuruya@intmed2.med.kyushu-u.ac.jp
Letters to the Editor
IgA nephropathy in cystic fibrosis
Abstract
Naveen Bhatt and Nidhi Bhatt
Letters to the Editor
Non-infectious, non-struvite staghorn calculi with coexisting vesical stone
Abstract
I.Y. Yun, S. Lee, K.P. Kang, W. Kim, Y.B. Jeong, Y.G. Kim and S.K. Park
Letters to the Editor
A dire knee pain hamstringing hemodialysis
