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Abstract

PHOS-FAKE or PHOS-FATAL – does intake of phosphate from foods lead to elevated plasma phosphate and its associated cardiovascular risks?

P.A. Davis, V. Savica and L.A. Calò

Email: renzcalo@unipd.it

Abstract

Clinical Nephrology, Vol. 74 – No. 1/2010 (4-11)

PA21: a novel phosphate binder for the treatment of hyperphosphatemia in chronic kidney disease

P. Geisser and E. Philipp

Research and Development Department, Vifor Pharma – Vifor International Inc,
St. Gallen, Switzerland
Aim: Limitations of conventional phosphate binders have led to the development of novel non-calcium, non-aluminium agents for use in patients with chronic kidney disease (CKD). The iron-based agent PA21 (stabilized polynuclear iron(III)-oxyhydroxide) has high phosphate binding capacity in vitro. This study was undertaken to investigate the uptake of iron after oral administration of PA21 in order to identify any potential risk of iron overload in the clinical setting, and to obtain a preliminary assessment of the effect of PA21 on serum phosphate levels prior to larger trials over a longer treatment period. Materials and methods: An open-label, Phase I study was undertaken in which PA21 10 g/day was administered for 7 days to 8 nondialysis-dependent CKD patients (Stages 3 – 4), 8 maintenance hemodialysis patients and 8 healthy subjects. In addition, a single dose of radiolabeled PA21 was administered to determine iron uptake. Results: Median iron uptake (range) was 0.06% (0.008 – 0.44%), 0.02% (0 – 0.04%) and 0.43% (0.16% – 1.25%) in the nondialysis-dependent CKD patients, hemodialysis patients and healthy subjects, respectively. Serum phosphate level decreased over the 7-day treatment period in the nondialysis patients (1.44 ± 0.29 mmol/l to 1.10 ± 0.27 mmol/l, p < 0.01) and the hemodialysis patients (2.85 ± 0.78 mmol/l to 2.25 ± 0.85 mmol/, p < 0.01). The most common adverse event was diarrhea (n = 9); all cases were mild to moderate. Conclusion: Findings from this short-term study indicate that PA21 may be an efficacious and well-tolerated phosphate binder with low iron uptake that may offer a promising alternative to existing hyperphosphatemia therapies. These results will need to be confirmed with longer-term, controlled studies.Correspondence to:
P. Geisser, PhD
Research and Development Department
Vifor Pharma - Vifor International Inc.
Rechenstrasse 37
9001 St Gallen, Switzerland
Email: Peter.Geisser@viforpharma.com

Abstract

Clinical Nephrology, Vol. 74 – No. 1/2010 (12-18)

Impact of phosphate binder type on coronary artery calcification in hemodialysis patients

R. Shantouf¹,²,³, N. Ahmadi¹, F. Flores¹, J. Tiano¹, A. Gopal¹, K. Kalantar-Zadeh¹,²,³ and M.J. Budoff²,³

¹Division of Cardiology, ²Harold Simmons Center for Kidney Disease Research and Epidemiology, Los Angeles Biomedical Research Institute at Harbor-UCLA, Torrance, and ³David Geffen School of Medicine, University of California Los Angeles, Los Angeles, CA, USA
Aims: In individuals with chronic kidney disease (CKD), including those undergoing maintenance hemodialysis (MHD), coronary artery calcification (CAC) is common. We hypothesized that, in MHD patients, intake of the calcium-free phosphate binder sevelamer is associated with lower CAC compared to calcium-based phosphate binders (CBPB). Material and methods: This is a cross-sectional study of MHD patients, who underwent computerized tomography to assess coronary artery calcium scores (CACS). Patients were stratified into two mutually exclusive groups based on taking only a CBPB vs. sevelamer. Logistic regression was used to calculate adjusted odds ratio (OR) of CACS >= 400, CACS 100 <=; CACS < 400, 10 <=; CACS < 100 vs. CACS < 10. Results: 117 MHD patients were either on a CBPB alone (n = 60) or sevelamer alone (n = 57). Despite increased prevalence of DM in the sevelamer group (58%) as compared to the CBPB group (35%), CACS was significantly lower with sevelamer use (283 ± 83 vs. 494 ± 94, p = 0.02). The OR of significant CACS >=; 400 vs. CAC < 10 was 4.35 (95% confidence interval: 1.5 – 9.9, p = 0.008) for CBPB compared with sevelamer, after controlling for case-mix, cholesterol-lowering medication, DM, and inflammatory markers. Conclusion: In our cohort, significant CAC was significantly more prevalent among MHD patients taking CBPB as compared to sevelamer monotherapy.Correspondence to:
M.J. Budoff, MD
Los Angeles Biomedical Research Institute at Harbor-UCLA
1124 W. Carson Street, RB2
Torrance, CA 90502, USA
Email: mbudoff@labiomed.org

Abstract

Clinical Nephrology, Vol. 74 – No. 1/2010 (19-24)

Seasonal variation of vitamin D in patients on hemodialysis

R. Tolouian¹, D.S. Rao², M. Goggins², S. Bhat² and A. Gupta³

¹Division of Nephrology and Hypertension, Texas Tech University Health Science Center at El Paso, TX, ²Divisions of Nephrology and Bone and Mineral Research Laboratory (D.S.R.), Henry Ford Hospital, Detroit, MI, and ³Rockwell Medical Technologies, Wixom, MI, USA
Background: Seasonal and racial differences in serum 25-hydroxyvitamin D levels have been studied extensively in the general population but not in patients with end-stage renal disease (ESRD). Methods: Serum 25-hydroxyvitamin D levels, the best available index of vitamin D nutrition, was measured at the end of summer (September) in 142 chronic hemodialysis patients and again at the end of winter (April) in 73 of these 142 patients, to determine the prevalence and risk factors for vitamin D deficiency. Results: The prevalence of vitamin D depletion, as defined by serum 25-hydroxyvitamin D level of less than 20 ng/ml (50 nmol/l), was 54% at the end of summer and further increased to 86% by the end of winter (p < 0.0001 summer vs. winter). We observed that women and African-Americans had a greater prevalence of hypovitaminosis D (p < 0.0002 and p < 0.001 for both comparisons, respectively). Surprisingly, diabetic status, age, and the duration of ESRD were not associated with a significant increase in risk of vitamin D depletion. Conclusion: Vitamin D depletion is present in about half of ESRD patients with marked seasonal variations. Patients with ESRD should have more frequent assessments of their vitamin D nutrition by serum 25-hydroxyvitamin D levels, and vitamin D supplementation should be routinely prescribed, which may prevent many of the complications related to vitamin D deficiency and secondary hyperparathyroidism.Correspondence to:
A. Gupta, MB,BS, MD, Office of Chief Scientific Officer
Rockwell Medical
30142 S. Wixom Rood
Wixom, MI 48393, USA
Email: agupta@rockwellmed.com

Abstract

Clinical Nephrology, Vol. 74 – No. 1/2010 (25-32)

The effects of changing vitamin D levels on anemia in chronic kidney disease patients: a retrospective cohort review

P.T. Lac¹, K. Choi², I.-A. Liu³, S. Meguerditchian¹, S.A. Rasgon¹ and J.J Sim¹

¹Nephrology, Kaiser Permanente Los Angeles Medical Center, Los Angeles, CA, ²Occidente College, Los Angeles, CA, and ³Research and Evaluation, Kaiser Permanente Southern California, Pasadena, CA, USA
Background: Investigate whether changes in vitamin D levels affected erythropoiesis stimulating agent (ESA) requirements in chronic kidney disease (CKD) patients with anemia. Methods: A retrospective cohort study of nondialysis-dependent patients with CKD of all stages. Patients were anemic and on ESA with at least 2 documented 25-hydroxylated vitamin D (D25) levels drawn 4 months apart. Patients were grouped based on the change in their D25 levels. The primary end point evaluated was absolute change in the ESA doses needed to maintain target hemoglobin levels between 11 and 12 g/dl. Results: A total of 153 patients met the inclusion criteria for analysis. With the exception of the normal-to-low D25 group, patients showed a trend toward lower ESA doses with time. The low-to-normal vitamin D group showed a significant reduction in dose of 24% (1,415 units, p = 0.025). The normal-to-low group, however, showed a 22% increase in dose of 1,270 units (NS). Levels of Ca, PTH, and iron indexes were similar across all groups. Conclusion: Our retrospective cohort study demonstrates an ESA sparing effect in patients with vitamin D deficiency after repletion to normal levels. Conversely, there was a trend toward increased ESA requirements in patients who became vitamin D deficient from a previously normal state.Correspondence to:
J.J. Sim, MD
2nd Floor Nephrology
Kaiser Permanente Los Angeles Medical Center
4700 Sunset Blvd.
Los Angeles, CA 90027, USA
Email: John.J.Sim@kp.org

Abstract

Clinical Nephrology, Vol. 74 – No. 1/2010 (33-38)

Using quantum dots as fluorescence probe to evaluate the immune complex deposits in paraffin-embedded sections

J. Zhu¹, H. Chen¹, ², G. Ding¹, X. Zhu³, R. Zhu² and H. Yang¹

¹Department of nephrology, Renmin Hospital of Wuhan University, ²Department of Pathology, School of Basic Medical Science, Wuhan University and Wuhan Tumor Nanometer Diagnosis Engineering Research Center, Wuhan, PR China
Objective: To detect the immune complex deposits in IgA nephropathy (IgAN) by using quantum dots (QDs)-labeled immunofluorescence technology and to evaluate its significance. Methods: Using the fluorescence property of QDs and indirect immunofluorescence methods to detect the IgA and complement C3 in formalin-fixed paraffin-embedded (FFPE) tissues of IgAN. Minimal change disease (MCD) was used as a control. Results: Immunoglobulin and a complement were significantly detected in IgAN and manifested as special distribution of intensive salmon pink fluorescence. Compared with fluorescein isothiocyanate (FITC) tagging, QD signal showed better specificity and signal to noise ratio, and QD signal was not significantly quenched after 60 min of excitation. Conclusion: QDs can be used to label subcellular proteins and have obvious advantages compared with the traditional organic fluorophores. QDs-tagged fluorescence can be applied as a new method for clinical labeling detection in renal pathology.Correspondence to:
Dr. G. Ding
Department of Nephrology
Renmin Hospital of Wuhan University
238 Jiefang Road
Wuhan 430060, Hubei Province, PR China
Email: chu778899@yahoo.com.cn

Abstract

Clinical Nephrology, Vol. 74 – No. 1/2010 (39-45)

Kidney allograft biopsy: timing to complications

Z. Yablon¹, P. Recupero¹, J. McKenna¹, J. Vella¹,² and M.G. Parker¹,²

¹Division of Nephrology and Transplantation, Maine Medical Center and ²Tufts University School of Medicine, Portland, ME, USA
Background: Clinical Practice guidelines recommend that patients be observed overnight after kidney biopsy based upon data that 1/3 of bleeding complications occur 12 hours post-procedure. Retrospective studies of same day discharge after kidney allograft biopsy suggest this practice may be safe, but no prospective studies to date have examined time to bleeding complications. Methods: We conducted a single center, prospective, observational study of adult outpatient kidney allograft recipients undergoing elective percutaneous allograft biopsy who were observed for 8 hours post-procedure before discharge home. Bleeding complications were characterized as minor or major and tracked by time post-biopsy. Baseline demographics were assessed for correlation with complications. Results: 8/124 (6.4%) of patients had a bleeding complication and 7/8 (87.5%) of complications occurred within the observation window. 3.2 % were minor and 3.2% were major complications with one major complication occurring after the 8-hour period. Neither the baseline demographics nor drop in serum hemoglobin of > 1 g/dl 6 hours after biopsy predicted a bleeding complication. However, a drop of > 1.5 g/dl correlated with a significant bleeding event (p = 0.006). Conclusions: An 8-hour observation window captures the majority of bleeding complications after adult kidney transplant biopsy.Correspondence to:
M.G. Parker, MD, Director
Division of Nephrology and Transplantation
Associate Professor of Medicine
Tufts University School of Medicine
Maine Medical Center
22 Bramhall Street
Portland, ME 04102, USA
Email: parkem@mmc.org

Abstract

Clinical Nephrology, Vol. 74 – No. 1/2010 (46-52)

Ultrasound as a diagnostic tool to differentiate acute from chronic renal failure

C.A. Ozmen¹, D. Akin², S.U. Bilek¹, A.H. Bayrak¹, S.Senturk¹ and H. Nazaroglu¹

¹Department of Radiology, ²Department of Nephrology, Dicle University School of Medicine, Diyarbakir, Turkey
Aim: Renal ultrasound (US) is the most appropriate method for imaging renal failure; however, considerable overlap in renal size and renal echogenicity exists between normally and abnormally functioning kidneys. We compared the sonographic features of kidneys in patients with renal failure to investigate the potential role of renal US to distinguish acute from chronic renal failure and assessed the diagnostic role of body surface area-corrected renal length compared to measured renal length. Materials and methods: We included 127 consecutive patients with serum creatinine levels higher than 3 mg/dl and 33 healthy volunteers. The subjects with acute renal failure (ARF) and chronic renal failure (CRF) were compared for renal length, parenchymal thickness, parenchymal echogenicity, distinctness of the corticomedullary junction, and the presence of stones and cysts. Results: No significant differences in age, serum albumin, creatinine, weight, height, or gender distribution were found between patients with ARF and those with CRF, except in serum hemoglobin. The right and left kidney parenchymal thickness and renal length were significantly greater in ARF patients than in those with CRF (p < 0.0001). The mean parenchymal thickness and renal length were similar in ARF patients and the control group. Grade I hyperechogenicity was the most common finding during sonography. Conclusions: Renal length, parenchymal thickness, and echogenicity differed significantly between patients with acute and chronic renal failure. A renal US examination is still the most appropriate method for imaging renal failure and should be combined with other tests to distinguish acute from chronic renal failure.Correspondence to:
Dr. C.A. Ozmen
Dicle University School of Medicine
Department of Radiology
21280 Diyarbakir, Turkey
Email: cihanakgul@gmail.com

Abstract

Clinical Nephrology, Vol. 74 – No. 1/2010 (53-58)

Resistance management in chronic hepatitis B complicated by renal failure

J. Wiegand¹, T. Karlas¹, I. Schiefke², U. Krasselt³, T. Bock⁴, J. Mössner¹ and H.L. Tillmann¹, ⁵

¹Department of Medicine & Dermatology, Division of Gastroenterology and Rheumatology, University of Leipzig, Leipzig, ²Center for Gastroenterology and Hepatology, Markkleeberg, ³Pharmacy Schlehenapotheke, Leipzig, ⁴Department of Molecular Pathology, Institute for Pathology, University of Tuebingen, Tuebingen, Germany and ⁵Duke Clinical Research Institute, Duke University Medical Center, Durham, NC, USA
Therapy of chronic hepatitis B has improved by the invention of the potent nucleos(t)ide analogues entecavir, telbivudine and tenofovir disoproxil. Due to increasing prevalence of lamivudine resistance the appropriate first line therapy may prevent emergence of any new resistance and avoid combination therapy. The present case describes a complex history of chronic hepatitis B in the setting of renal failure after two renal transplants illustrating why lamivudine should not be used as first line treatment option any more. Instead, entecavir offers high antiviral potency, low risk for resistance and possible individual dose titration by an oral solution.Correspondence to:
Dr. med. J. Wiegand
Department of Medicine & Dermatology
Division of Gastroenterology & Rheumatology
University of Leipzig
Liebigstrasse 20
04103 Leipzig, Germany
Email: johannes.wiegand@medizin.uni-leipzig.de

Abstract

Clinical Nephrology, Vol. 74 – No. 1/2010 (59-64)

Successful hemodialysis in a phenytoin overdose: case report and review of the literature

M. Ghannoum¹, S. Troyanov², P. Ayoub¹, V. Lavergne³ and T. Hewlett⁴

¹Division of Nephrology, Verdun Hospital, University of Montreal, Verdun, Quebec, ²Division of Nephrology, ³Division of Medical Biology, Sacré-Cœur Hospital, University of Montreal, Montreal, Quebec, and ⁴Division of Nephrology, Cape Breton Regional Hospital, Sydney, Nova-Scotia, Canada
We describe the case of a 42-year-old female who presented to our care 1 hour after ingesting 3.6 g of phenytoin. She was stuporous 48 hours after admission despite supportive therapy. She was treated with hemodialysis (HD) for nearly 6 hours in order to remove phenytoin. Her level of consciousness improved markedly during the procedure. During HD, phenytoin levels decreased by 47% and measured half-life was 6.8 hours as compared to 116 hours when not on HD. Finally, we were able to remove 547 mg of phenytoin (directly measured from the dialysate), representing approximately a third of estimated body stores. The use of extracorporeal therapy in phenytoin overdose is reviewed here. We believe that in severe cases of phenytoin intoxication, hemodialysis can be used to accelerate total body burden of the drug, even if protein binding is significant.Correspondence to:
Dr. M. Ghannoum
Centre hospitalier de Verdun
4000 Boul. Lasalle, Verdun,
Quebec, H4G2A3, Canada
Email: marcghannoum@gmail.com

Abstract

Clinical Nephrology, Vol. 74 – No. 1/2010 (65-69)

Kidney transplant: a unique cure for severe nonischemic cardiac dysfunction

S. Sajid¹, N. Nickolay² and S. Bhandari¹

¹Department of Renal Medicine, and ²Department of Academic Cardiology, Hull and East Yorkshire Hospitals NHS Trust, Hull, UK
Cardiovascular complications are the leading cause of mortality among patients with end-stage renal disease, accounting for 50% of all deaths. The prevalence of heart failure amongst these patients is as high as 40% and is responsible for 12% of the total deaths. The mechanisms underlying these cardiac abnormalities remain unclear. Renal transplantation is normally contraindicated. We present a case of a hemodialysis patient with nonischemic severe cardiac dysfunction and chronic poor compliance with salt and water restriction, who demonstrated significant functional and clinical improvement after renal transplantation assessed by echocardiography, cardiac MRI, symptoms and number of hospital admissions. This case highlights the beneficial impact of renal transplantation in a young patient with uncontrollable chronic salt and water overload and nonischemic cardiac dysfunction. Despite the overt clinical and radiological severity in this case, use of scoring systems such as the Northern Regional Risk index demonstrated a low-to-medium risk during transplant assessment. Therefore, individualizing patients during pretransplant assessment and use of scoring systems may assist in further selection of appropriate patients for potential renal transplantation.Correspondence to:
Dr. S. Bhandari
Department of Renal Medicine
Hull and East Yorkshire Hospitals NHS Trust
Hull York Medical School
Kingston upon Hull, UK
Email: Sunil.Bhandari@hey.nhs.uk

Abstract

Clinical Nephrology, Vol. 74 – No. 1/2010 (70-73)

Mannitol-induced acute renal failure

S.-F. Tsai¹ and K.-H. Shu¹,²

¹Department of Medicine, Division of Nephrology, Taichung Veterans General Hospital, and ²School of Medicine, Chung-Shan Medical University, Taichung, Taiwan
A 62-year-old man was admitted to the ophthalmologic department for operation of retinal detachment. Mannitol and acetazolamide were prescribed to reduce intraocular pressure. Seven days after operation, gradual onset of drowsy consciousness occurred. The laboratory findings of hypertonic hyponatremia (109 mEq/l), hyperosmolality (341 mosm/kg), metabolic acidosis (pH: 7.17) and acute renal failure (serum creatinine: 8.2 mg/dl) dictated a diagnosis of mannitol-induced acute kidney injury. First, 3% saline was given, but consciousness kept deteriorated with worsened dyspnea and metabolic acidosis. Hemodialysis was then performed subsequently and his consciousness and renal function completely recovered. A special emphasis on the treatment of hypertonic hyponatremia was given.Correspondence to:
K.-H. Shu, MD
Division of Nephrology
Department of Medicine
Taichung Veterans General Hospital
No. 160, Section 3, Chung-Kang Road
Taichung, 407, Taiwan
Email: khshu@vghtc.gov.tw

Abstract

Clinical Nephrology, Vol. 74 – No. 1/2010 (74-80)

Tubulointerstitial nephritis with IgM-positive plasmacytoid large lymphocyte infiltration in a patient with primary biliary cirrhosis and Sjögren's syndrome

N. Takahashi¹, H. Kimura¹, Y. Kawajiri¹, D. Mikami¹, C. Yamamoto¹, K. Kasuno¹, N. Imai², T. Kuroda², S. Nishi², M. Yamamoto³ and H. Yoshida¹

¹Division of Nephrology, Department of General Medicine, Faculty of Medical Sciences, University of Fukui, Fukui, ²Division of Clinical Nephrology and Rheumatology, Niigata University Graduate School of Medical and Dental Sciences, Niigata, and ³Department of Internal Medicine, Fukui Kosei Hospital, Fukui, Japan
We report a 38-year-old woman diagnosed with tubulointerstitial nephritis (TIN) on renal biopsy, followed by being diagnosed with primary biliary cirrhosis (PBC) and Sjögren’s syndrome (SS). Immunohistochemically, the cellular infiltrates in TIN were mainly composed of small lymphocytes and IgM-positive plasmacytoid large lymphocytes. IgM-positive plasmacytoid large lymphocytes were not identical with, but colocalized with CD3- or CD20-positive lymphocytes. TIN in patients with PBC is very rare and little is known about immunohistochemical characteristics of infiltrating cells in this setting. To our knowledge, this is the first report demonstrating predominant infiltrating of IgM-positive plasmacytoid large lymphocytes in TIN due to PBC and SS.Correspondence to:
H. Yoshida, MD, PhD, Professor
Division of Nephrology
Department of General Medicine
Faculty of Medical Sciences
University of Fukui
Fukui, 910-1193, Japan
Email: hayoshi@u-fukui.ac.jp

Abstract

Anti-proteinuric effect of mizoribine monotherapy in three patients with membranous nephropathy

T. Fujita, C. Shimizu, K. Ito, Y. Fuke, A. Satomura and K. Matsumoto

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Volume 74, No. 1/2010(July)