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Abstract

Clinical Nephrology, Vol. 76 – No. 4/2011 (259-265)

Effect of cinacalcet on bone mineral density of the radius in hemodialysis patients with secondary hyperparathyroidism

E. Ishimura¹, S. Okuno³, N. Tsuboniwa³, M. Ichii², K. Yamakawa³,T. Yamakawa³, S. Shoji³, Y. Nishizawa² and M. Inaba²

¹Department of Nephrology, ²Department of Metabolism, Endocrinology, and Molecular Medicine, Osaka City University Graduate School of Medicine, and ³Shirasagi Hospital, Osaka, Japan
Background/Aim: Cinacalcet, an allosteric modulator of the calcium sensing receptor, effectively reduces serum parathyroid hormone (PTH) in patients with secondary hyperparathyroidism. It is not well known whether bone mineral density (BMD) of hemodialysis patients with secondary hyperparathyroidism is altered after cinacalcet treatment. Methods: The BMD in the distal 1/3 of the radius and in the ultradistal radius, which are enriched with cortical and cancellous bone, respectively, was examined by dual X-ray absorptiometry, 1 year prior to, at the start, and 1 year after cinacalcet treatment, in 61 patients. Results: The BMD of both the distal 1/3 and ultradistal radius decreased significantly in the year prior to cinacalcet treatment (p < 0.01). However, the BMD at either site did not change significantly in the year after cinacalcet treatment. The annual changes in the BMD of the distal 1/3 radius increased significantly from –0.023 ± 0.029 g/cm²/year to –0.002 ± 0.033 g/cm²/year, prior to and after cinacalcet treatment, respectively; however, the annual changes in the BMD of the ultradistal radius did not change significantly prior to and after cinacalcet treatment. Conclusion: There was a significant association between cinacalcet treatment and reduction in BMD loss in patients with secondary hyperparathyroidism. Cortical bone, rather than cancellous bone, was particularly affected by cinacalcet treatment.Correspondence to:
E. Ishimura, MD, PhD
Department of Nephrology
Osaka City University
Graduate School of Medicine
1-4-3, Asahi-machi, Abeno-ku
Osaka 545-8585, Japan
Email: ish@med.osaka-cu.ac.jp

Abstract

Clinical Nephrology, Vol. 76 – No. 4/2011 (266-272)

A study of maintenance therapy after intravenous maxacalcitol for secondary hyperparathyroidism

M. Adachi¹, T. Miyoshi¹, N. Shiraishi¹, H. Shimada², S. Sakaguchi³, K. Tomita¹ and K. Kitamura¹

¹Department of Nephrology, Kumamoto University Graduate School of Medical Sciences, ²Josuikai Shimada Hospital, Kumamoto and ³Gyokuwakai Midorigaoka Clinic, Arao, Japan
Aim: Intravenous vitamin D therapy is an established treatment for secondary hyperparathyroidism (SHPT). However, no protocols have been established for maintenance therapy with intravenous or oral vitamin D after control of intact parathyroid hormone (iPTH) within the target range. Methods: Step I. For patients with SHPT (200 ≤ iPTH ≤ 500 pg/ml), a dose of 2.5 mg maxacalcitol (OCT) was administered intravenously three times a week with oral sevelamer hydrochloride; the dose was increased to a 10 µg maximum three times a week to control iPTH to < 150 pg/ml. Step II. When iPTH reached the target level, patients were assigned to Group A (oral alfacalcidol 1.0 µg/day) or B (oral alfacalcidol 0.25 µg/ day). Serum iPTH, calcium, and inorganic phosphorus were measured each month for 6 months. Maintenance rates for the target iPTH levels were evaluated, < 150 pg/ml at Step I and < 200 pg/ml at Step II. Results: iPTH decreased to < 150 pg/ml by OCT in 24 of 35 patients (68.6%). During the 24-week observation period, iPTH was controlled for 83.3% patients in Group A vs. 36.4% for Group B (p < 0.05). No dropouts due to hypercalcemia or hyperphosphatemia occurred. Conclusion: OCT dose titration was effective for SHPT. A higher daily dose of oral alfacalcidol (1.0 µg) appears to be more effective than a lower dose (0.25 µg) as maintenance therapy after iPTH control.Correspondence to:
M. Adachi, MD, PhD, Assistant Professor
Department of Nephrology
Kumamoto University Graduate
School of Medical Sciences
1-1-1 Honjo, Kumamoto
Kumamoto 860-8556, Japan
Email: m-adachi@gpo.kumamoto-u.ac.jp

Abstract

Clinical Nephrology, Vol. 76 – No. 4/2011 (273-283)

ACEI and ARB combination therapy in patients with macroalbuminuric diabetic nephropathy and low socioeconomic level: a double-blind randomized clinical trial

S.M. Titan, J.M. Vieira Jr., W.V. Dominguez, R.T. Barros and R. Zatz

Renal Division, Department of Clinical Medicine, Faculty of Medicine, University of São Paulo, Brazill
Objective: The combination of an ACE inhibitor (ACEI) and an angiotensin II receptor blocker (ARB) has been proposed for the treatment of diabetic nephropathy (DN), but doubts remain about its efficacy and safety. We compared the effects of combination therapy and ACEI monotherapy on proteinuria and on three urinary inflammatory cytokines (MCP-1, TGF-β and VEGF). Design and patients: 56 patients with macroalbuminuric DN received 40 mg/d enalapril for 4 months, followed by add-on 100 mg/day losartan or placebo for another 4 months. The primary and secondary endpoints were reduction of proteinuria and cytokine levels, respectively. Results: Proteinuria did not fall in either group. Repeated measures ANOVA revealed no difference between groups. A high side effect rate was observed (28.5%). Finally, unadjusted logistic regression showed no difference between groups, but after adjustments the risk of worsening proteinuria was higher in the combination therapy group (p = 0.04). The same pattern was observed for urinary MCP- 1. Conclusion: These results suggest that 1) in advanced DN with severe proteinuria and poor metabolic control, angiotensin II blockade may be less effective than in other groups of CKD patients. 2) In such patients, combination therapy may not afford superior renoprotection compared to enalapril. 3) Urinary MCP-1 is a promising biomarker for the response to ACEI and/or ARB treatment and for the risk of associated unwanted effects. Correspondence to:
S. Titan, MD, PhD
Av Dr Enéas de Carvalho Aguiar, 255
Nephrology Department
São Paulo, SP, 05403-000, Brazil

Email: silviatitan@superig.com.br

Abstract

Clinical Nephrology, Vol. 76 – No. 4/2011 (284-289)

Serum accumulation of a creatinine oxidative metabolite (NZ-419: 5-hydroxy-1- methylhydatoin) as an intrinsic antioxidant in diabetic patients with or without chronic kidney disease

G. Hasegawa¹, K. Nakano² and K. Ienaga³

¹Department of Endocrinology and Metabolism, Kyoto Prefectural University of Medicine Graduate School of Medical Science, ²Yamashiro Country Hospital, Kyoto, and ³Nippon Zoki Pharmaceutical Co. Ltd., Osaka, Japan
Aims: In mammals, creatinine (Cr) is catabolized by a dual oxidative pathway via 5-hydroxy-1-methylhydantoin or 5-hydroxycreatinine. The former, an intrinsic antioxidant, termed NZ-419, has been reported to prevent the progression of chronic renal failure in animal models. However, its clinical intrinsic serum level has not yet been reported. Methods: We analyzed serum NZ-419 levels in diabetic and nondiabetic patients with or without Stage 3 – 5 chronic kidney disease (CKD). Results: The levels of NZ-419 in diabetic patients with (88.1 ± 17.2 µg/dl, p < 0.001) or without (31.5 ± 2.4 µg/dl, p < 0.05) Stage 3 – 5 CKD were significantly higher than in nondiabetic normal controls (9.0 ± 5.6 µg/dl). The molar ratio data showed NZ-419/Cr was significantly higher in both diabetic patients with (p < 0.01) or without Stage 3 – 5 CKD (p < 0.001) compared to nondiabetic normal controls. No further increase occurred with increasing severity of renal failure. Furthermore, nondiabetic patients with or without Stage 3 – 5 CKD did not show significantly different molar ratio values than controls but had significantly higher values of NZ-419 levels (p < 0.001). Conclusions: Overproduction and decreased clearance played a major role in the increased NZ-419 levels we observed in the patients with diabetes and Stage 3 – 5 CKD, respectively. The existence of chronic renal failure did not further enhance this overproduction.Correspondence to:
Dr. G. Hasegawa
Department of Endocrinology and Metabolism
Kyoto Prefectural University of Medicine
Graduate School of Medical Science
Kamigyo-ku, Kyoto 602-8566, Japan
Email: goji@koto.kpu-m.ac.jp

Abstract

Clinical Nephrology, Vol. 76 – No. 4/2011 (290-295)

Carotid intima-media thickness and cerebral white matter lesions are more advanced in acute ischemic stroke patients with renal dysfunction

K. Ueda, Y. Watanabe, T. Katsumata, T. Kaneko, T. Otori, K. Utsumi, Y. Iino and Y. Katayama

Department of Internal Medicine, Division of Neurology, Nephrology, and Rheumatology, Nippon Medical School, Tokyo, Japan
Background: It has been shown that chronic kidney disease (CKD) is a risk factor for stroke, but there have been few studies on the relationship between CKD and stroke. The objective of this study was to investigate the relationship between renal dysfunction and cerebral white matter lesions or carotid plaque in patients with acute ischemic stroke. Methods: Subjects were 202 consecutive patients with ischemic stroke who were admitted to the Stroke Center of Nippon Medical School Hospital from January 2007 to July 2008. The estimated glomerular filtration (eGFR) was calculated and the relationship of renal dysfunction to the subtype of ischemic stroke, cardiovascular risk factors, cerebral white matter lesions on brain magnetic resonance imaging (MRI), and maximum intima-media thickness (IMT) of the carotid artery was analyzed statistically. Results: Among the 202 patients with ischemic stroke, 27.9% had an eGFR < 60 ml/min/1.73 m² (eGFR < 60 ml group). Age was significantly higher and a history of hypertension, diabetes, and ischemic heart disease was significantly more frequent in this group than in the group with eGFR ≥ 60 ml/min/1.73 m² (eGFR ≥ 60 ml group). Among the subtypes of ischemic stroke, atherothrombotic cerebral infarction was predominant and accounted for 41.1%, followed by cardiogenic cerebral infarction at 31.1%, lacunar infarction at 18.8%, and unclassified infarction at 8.9%. There was no significant difference in the distribution of ischemic stroke subtype between both groups. Deep and subcortical white matter hypertensity (DSWMH) and periventricular hyperintensity (PVH) were detected by brain MRI in 91.5% of the eGFR < 60 ml group. In the eGFR < 60 ml group, PVH was significantly more frequent than in the eGFR ≥ 60 ml group (p = 0.032) and DSWMH was also more frequent (p = 0.0519). The maximum IMT measured by carotid ultrasound was significantly larger in the eGFR < 60 ml group. Conclusion: In patients with acute ischemic stroke, the incidence of renal dysfunction was high like that of heart disease. In the eGFR < 60 ml group, carotid IMT was larger and the incidence of PVH was higher, so these patients presumably had more advanced atherosclerotic changes of the cerebral vessels.Correspondence to:
K. Ueda
1-1-5, Sendagi, Bunkyo-ku
Tokyo, 113 -8603, Japan
Email: kae@gd6.so-net.ne.jp

Abstract

Clinical Nephrology, Vol. 76 – No. 4/2011 (296-305)

Distribution of reference GFR in a development population – a critical factor for the establishment of a GFR estimation equation

Y.-C. Ma¹*, L. Zuo²*, Z.-M. Su¹, L. Chen², S. Meng¹, J.-J. Li¹, C.-L. Zhang² and H.-Y. Wang²

¹Department of Nephrology, China Rehabilitation Research Center, BeiJing BoAi Hospital, Capital Medical University Rehabilitation Medical College and ²Institute of Nephrology, Peking University First Hospital, Key Laboratory of Ministry of Health, Beijing, PR China

*These authors contributed equally to this work.
Background and aim: Our previous work showed that the performance of MDRD equations could be improved by modifying the original MDRD equation. However, during the modification we recognized that reference GFR (rGFR) distribution was not similar between the MDRD study and the Chinese Estimating GFR (eGFR) Investigation Study. This present study was designed to illustrate that the GFR estimating equation might be influenced by the difference of rGFR distribution in the development population. Racial factors might not be as important as once thought. Patients and methods: The Chinese eGFR Investigation Study dataset containing 684 CKD patients was defined as Dataset I, the modified MDRD equation for Chinese was defined as Equation 1. Datasets II and III were generated respectively by deleting 125 cases of CKD Stage 1 from Dataset I and by adding 297 cases of apparently healthy Chinese adults into Dataset I. eGFR was estimated using Equation 1. Using rGFR as dependent and eGFR as independent, linear regression models were constructed using Dataset II and Dataset III, respectively, and generated Equation 2 and Equation 3. The prevalence of eGFR less than 60 ml/min/1.73 m² in the adult Beijing population was calculated using Equation 1, 2 and 3. Results: The previous reported prevalence of decreased GFR using Equation 1 in the Beijing adult population was 1.3% (0.8 – 1.8). By using Equation 2 and Equation 3, the prevalence increased to 3.2% (2.49 – 4.13) and decreased to 0.8% (0.57 – 1.28), respectively. Conclusions: GFR estimating equation was influenced by rGFR distribution of the development dataset.Correspondence to:
J.-J. Li, MD
China Rehabilitation, Research Center
Beijing BoAi Hospital
Capital Medical University Rehabilitation Medical College
No 10, Jiao Men North Street, FengTai District
Beijing, China,100068
Email: crrcrenal@163.com

Abstract

Clinical Nephrology, Vol. 76 – No. 4/2011 (306-313)

Outcome of peritoneal dialysis in cirrhotic patients with end-stage renal disease – a 24-years’ experience in Taiwan

S.-T. Huang¹, Y.-W. Chuang¹, C.-H. Cheng¹,²,⁵, M.-J. Wu¹,⁴, C.-H. Chen¹,³,⁶, T.-M. Yu¹,³ and K.-H. Shu¹,²

¹Division of Nephrology, Department of Medicine, Taichung Veterans General Hospital, ²School of Medicine, Chung-Shan Medical University, ³School of Medicine, China Medical University, ⁴Institute of Clinical Medicine, National Yang Ming University, ⁵Department of Biotechnology, Hung Kuang University, and ⁶Department of Life Science, Tunghai University, Taichung, Taiwan
Background: Use of peritoneal dialysis (PD) in liver cirrhosis patients with end-stage renal disease remains controversial. Moreover, the long-term outcome in cirrhotic patients is unclear. The aim of the present study was to analyze the outcome of cirrhotic patients treated with PD in our center during the past 24 years. Methods: We retrospectively reviewed the data of cirrhotic patients who received PD between 1984 and 2009. A group of noncirrhotic patients who were age- and sex-matched during the same period were selected as controls. Peritonitis rates, complications and outcomes were compared. Results: A total of 30 cirrhotic patients and 60 control patients were included in the analysis. Peritonitis-free survival did not differ between groups. Gram-positive organisms, especially coagulase-negative staphylococcus and streptococcus sp., were the major causes of peritonitis in the cirrhotic patients. Also in the cirrhotic patients, complications such as umbilical hernia, chronic hypotension and erythropoietin resistance were more common as compared with controls. An initially higher solute and water transport capacity was observed in the cirrhotic patients, which became comparable to controls by the end of the 2nd year of treatment. Serum albumin concentrations were lower in cirrhotic patients (p = 0.01), and the decline of renal Kt/V was slower in cirrhotic patients as compared to that of controls (p < 0.0001). There was no significant difference in patient and technique survival between the two groups. Conclusion: Our study suggests that PD is an effective therapy with a comparable risk of peritonitis and solute clearance in liver cirrhosis patients with end-stage renal failure.Correspondence to:
K.-H. Shu, MD
Division of Nephrology
Department of Medicine
Taichung Veterans General Hospital
No.160, Sec.3, Chung-Kang Road
Taichung, 40705, Taiwan
Email: khshu@vghtc.gov.tw

Abstract

Clinical Nephrology, Vol. 76 – No. 4/2011 (314-322)

Effects of conventional versus biocompatible peritoneal dialysis solutions on peritoneal and systemic inflammation, malnutrition and atherosclerosis in CAPD patients

V. Stankovic-Popovic¹, V. Nesic², D. Popovic³, D. Maksic⁴, M. Colic⁵, S. Vasilijic⁵, Z. Vucinic⁶, B. Milicic⁷, S. Radjen⁸ and N. Dimkovic¹

¹Clinical Department for Renal Diseases, Zvezdara University Medical Center, ²Institute for Urology and Nephrology, ³Clinic for Gastroenterology, UCC of Serbia, ⁴Diagnostic-Outpatient Center, ⁵Institute for Medical Research, ⁶Department of Functional Diagnostics in Cardiology, Military Medical Academy, Belgrade, ⁷Department of Medical Informatics, School of Dentistry, and ⁸ Institute for Hygiene, Military Medical Academy, Belgrade, Serbia
Background: Chronic inflammation, malnutrition and atherosclerosis (MIA syndrome) are important predictors of high mortality in continuous ambulatory peritoneal dialysis (CAPD) patients. We aimed to evaluate the effects of PD solutions (standard vs. biocompatible) on some parameters of MIA syndrome in patients undergoing CAPD. Methods: 42 stable patients who were on CAPD at least 2.5 years participated in this cross-sectional study. Patients who had severe anemia (Hb < 10 g/l), immunomodulatory therapy, peritonitis or any inflammatory conditions for at least 3 months before the analysis, malignant disease and acute exacerbation of heart failure, were excluded. 21 (50%) patients were treated with standard PD solutions (CAPDP-1), while the remaining 21 (50% of patients) were treated with biocompatible PD solutions (neutral solutions with lower level of glucose degradation products and lower concentration of calcium, CAPDP-2). All patients underwent echocardiography and B-mode ultrasonography of common carotid arteries together with assessments of nutrition status and parameters of systemic and local inflammation. Results: There were no significant differences between the groups concerning age, gender, underlying disease, residual renal function, peritoneal transport characteristics, comorbidity or therapy applied. Patients from group CAPDP-2 had a significantly lower serum level of hs-CRP (3.7 ± 2.6 mg/l vs. 6.3 ± 4.5 mg/l; p = 0.023) and significantly better nutritional status confirmed by mid-arm circumference (p = 0.015), mid-arm muscle circumference (p = 0.002) and subjective global assessment (14.28% of patients in CAPDP-2 vs. 71% of patients in CAPDP-1 were malnourished; p = 0.000). Group CAPD-2 had less frequent left ventricular hypertrophy (p = 0.039), thinner intima-media thickness (p = 0.005), smaller carotid narrowing (p = 0.000) and fewer calcified plaques of common carotide arteries (p = 0.003). No significant difference between the CAPDP groups was observed in serum and effluent levels of inflammatory cytokines (IL-1, IL-6 and TNF-α) and CA-125 effluent level. Logistic regression analysis did not confirm that biocompatibility of PD solutions was an independent predictor of any parameter of MIA syndrome. Conclusions: According to the present study and logistic regression analysis, the effect of biocompatible CAPD solutions on parameters of malnutrition, inflammation and atherosclerosis have to be confirmed by well-designed and controlled studies in a higher number of patients.Correspondence to:
V. Stankovic-Popovic, MD
Clinical Department for Renal Diseases
Zvezdara University Medical Center
161, Dimitrija Tucovica Street
11 000 Belgrade, Serbia
Email: drendo@beotel.rs

Abstract

Clinical Nephrology, Vol. 76 – No. 4/2011 (323-329)

Lecithin-cholesterol acyltransferase (LCAT) deficiency without mutations in the coding sequence: a case report and literature review

K. Shoji¹, H. Morita¹,⁵, Y. Ishigaki², C.J. Rivard³, M. Takayasu¹, K. Nakayama¹, T. Nakayama¹, Y. Inoue¹, M. Ayaki⁴ and A. Yoshimura

¹Division of Nephrology, Department of Medicine, Showa University Fujigaoka Hospital, Yokohama, ²Division of Molecular Metabolism and Diabetes, Department of Internal Medicine, Tohoku University Graduate School of Medicine, Sendai, Japan, ³Division of Renal Diseases and Hypertension, University of Colorado Denver, Aurora, Colorado, USA, ⁴Department of Ophthalmology Showa University Fujigaoka Hospital, Yokohama, and ⁵Division of Nephrology and Rheumatology, Department of Internal Medicine, Aichi Medical University, School of Medicine, Nagakute, Japan
Familial lecithin-cholesterol acyltransferase (LCAT) deficiency (FLD) is a rare genetic disease characterized by corneal opacities, normocytic anemia, dyslipidemia, and proteinuria progressing to chronic renal failure. In all FLD cases, a mutation has been found in the coding sequence of the LCAT gene. FLD is clinically distinguished from an acquired form of LCAT deficiency by the presence of corneal opacities. Here we describe a 36-year-old woman presenting with clinical, pathological, and laboratory data compatible with FLD. Her mother and elder sister had corneal opacities. However, genetic analysis revealed there were no mutations in the LCAT coding sequences and no alterations in LCAT mRNA expression. Furthermore, we were unable to find any underlying conditions that may lead to LCAT deficiency. The present case therefore demonstrates that LCAT deficiency may be caused by factors other than mutations in the coding sequence and we suggest that a translational or posttranslational mechanism may be involved.Correspondence to:
H. Morita, MD
Division of Nephrology and Rheumatology
Department of Internal Medicine
Aichi Medical University
School of Medicine, Nagakute, Japan
Email: moritahi@aichi-med-u.ac.jp

Abstract

Clinical Nephrology, Vol. 76 – No. 4/2011 (330-333)

Young woman with branchio-oto-renal syndrome and a novel mutation in the EYA-1 gene

E. Nardi, A. Palermo, P. Cusimano, G. Mulè and G. Cerasola

Cattedra di Medicina Interna, Dipartimento di Medicina Interna, Malattie Cardiovascolari e NefroUrologiche, Excellence Center of the European Society of Hypertension, Università degli Studi di Palermo, Italy
Branchio-oto-renal (BOR) syndrome is an autosomal dominant disease clinically characterized by the coexistence of some or all of the following major disorders: deafness, cervical branchial fistulae, preauricular pits, and renal abnormalities. Most families with BOR syndrome have mutations on the EYA-1 gene on chromosome 8q. We present the case of a 23-year-old Italian woman without a familial history of BOR syndrome. The patient, who had hearing loss and a history of surgeries for correction of bilateral cervical branchial fistulae and bilateral preauricular pits, presented with renal impairment, hypertension and overt proteinuria. DNA sequencing showed a novel heterozygous mutation 1420-1421delCC in exon 14 of EYA-1 gene.Correspondence to:
E. Nardi, MD
Via Alcide De Gasperi 30
90146 Palermo, Italy
Email: emilionardi@virgilio.it

Abstract

Clinical Nephrology, Vol. 76 – No. 4/2011 (334-339)

Bilateral renal artery dissection following extreme exertion

S. Baroudi¹, B. Bastani¹, N. Balci², B.K. Bieneman², P. Sobti³ and G.C. Kudva⁴

¹Division of Nephrology, ²Department of Radiology, Saint Louis University School of Medicine, St Louis, ³Consultant Hematologist Oncologist, Cape Girardeau, and ⁴Division of Hematology/Oncology Saint Louis University School of Medicine, St.Louis, MO, USA
Dissection of a renal artery is rare and is usually associated with underlying arterial disease. Bilateral renal artery dissection following extreme exertion is exceptionally uncommon, and thus presents a diagnostic challenge. We report a case of a middle-aged, otherwise healthy man who presented to the hospital with left flank pain after a long bicycling trip. Initial laboratory tests and urinalysis were normal. Careful review of a contrast-enhanced computed tomography angiogram (CTA) with 3D reconstruction revealed bilateral segmental renal artery dissection and thrombosis with corresponding renal infarcts. He was treated medically and rapidly recovered.Correspondence to:
S. Baroudi, MD
4254 W. Woods Edge Ln
Muncie, IN 47304, USA
Email: drbaroudis@gmail.com

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Volume 76, No. 4/2011(October)