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Abstract

Clinical Nephrology, Vol. 75 – No. 1/2011 (1-7)

Difference in coronary artery intima and media calcification in autopsied patients with chronic kidney disease

H. Yoshida¹, K. Yokoyama¹, T. Yaginuma¹, I. Ohkido¹, H. Yamamoto¹, Y. Utsunomiya¹, M. Kawakami² and T. Hosoya¹

¹Division of Kidney and Hypertension, Department of Internal Medicine, The Jikei University School of Medicine, Tokyo, and ²Department of Pathology, Seirei Sakura Citizen Hospital, Sakura, Japan
Background: In patients with chronic kidney disease (CKD), coronary artery calcification occurs at two distinct sites in the vessel wall: the intima and the media. Arterial media calcification (AMC), a nonocclusive condition, affects hemodynamics differently compared to arterial intima calcification (AIC), which occurs in atherosclerotic plaques. Arterial calcification is considered a cell-regulated process resembling intramembranous bone formation. The purpose of this retrospective observational study was to clarify the morphological differences between AIC and AMC and to evaluate the role of vascular smooth muscle cells (VSMCs) and macrophages in AIC and AMC formation. Methods: We histologically analyzed 14 tissue specimens from 14 autopsies of patients with CKD Stage 5D who underwent hemodialysis and 5 specimens from 5 patients with CKD Stage 2 – 3 (90 ml/min/1.73 m² > estimated GFR >= 30 ml/min/1.73 m²). We performed immunohistochemical staining of osteopontin (OPN) as a marker for bone matrix protein, alpha-smooth muscle actin (alphaSMA) for VSMCs, Cbfa1/Runx2 as a marker for osteoblastic differentiation of VSMCs, and CD68 for macrophages. Results: In the CKD 2/3 group, we also found AIC and AMC. OPN and CD68 expression in the CKD 2/3 group was similar to that in the CKD 5D group. Although we did not find Cbfa1/Runx2 positive cell expression in the CKD 2/3 group, we did find it in the CKD 5D group. We found CD68-positive cells predominantly in AIC and absent in AMC in both groups. Conclusions: These findings suggest that the influence of Cbfa1/Runx2 pathway in coronary artery calcification depends on the CKD Stage. Expression of CD68-positive cells depends on the location of the coronary artery calcification.Correspondence to:
H. Yoshida, MD
Division of Kidney and Hypertension
Department of Internal Medicine
The Jikei University School of Medicine
3-25-8, Nishi-Shinbashi, Minato-ku
Tokyo, 105-8471, Japan
Email: hiraku@jikei.ac.jp

Abstract

Clinical Nephrology, Vol. 75 – No. 1/2011 (8-15)

Sodium thiosulfate-based treatment in calcific uremic arteriolopathy: a consecutive case series

A.R. Sood¹,²,⁵, L.D. Wazny¹,³,⁵, C.B. Raymond¹,³,⁵, K. Leung⁵, P. Komenda¹,⁴, M. Reslerova¹,⁴, M. Verrelli¹,⁴, C. Rigatto¹,⁴ and M.M. Sood¹,⁴

¹Manitoba Renal Program, ²Department of Pharmacy, St. Boniface General Hospital, ³Department of Pharmaceutical Services, Health Sciences Centre, ⁴Section of Nephrology, University of Manitoba, and ⁵University of Manitoba, Winnipeg, Manitoba, Canada
Background: Calcific uremic arteriolopathy (CUA) is a rare complication in end stage renal disease with high mortality. Numerous case reports and one case series of 3 patients report the benefit of sodium thiosulfate (STS) for treatment of CUA. The purpose of this evaluation was to examine the response to a STS-based treatment approach in patients with CUA with 1 year follow up. Methods: A retrospective case series of 6 consecutive patients from Manitoba, Canada who met predefined diagnostic criteria for CUA and received STS between 2006 and 2008 were included. STS responders were defined as improvement in at least one of the following three parameters: pain severity, wound size and diagnostic imaging/radiography. Mortality, STS dose, duration, adverse events and cost were also collected. Results: Four patients were classified as responders. The 2 responders who survived at 1 year of follow-up demonstrated an improvement in all 3 parameters examined including an improvement in their follow-up diagnostic imaging results within the first 4 – 6 weeks of STS treatment. At 1 year of follow-up, 3 patients died. Conclusion: Using an STS-based multifaceted treatment approach for CUA, 4 patients responded but 3 of 6 patients died within 1 year. Further larger prospective studies are needed to delineate STS responders from non-responders.Correspondence to:
M.M. Sood, MD, FRCPC
St. Boniface General Hospital
409 Tacé Avenue
Winnipeg, Manitoba, Canada
Email: msood@sbgh.mb.ca

Abstract

Clinical Nephrology, Vol. 75 – No. 1/2011 (16-25)

Impact of immunosuppressive therapy on hepatitis C infection after renal transplantation

A. Kahraman¹, O. Witzke², A. Scherag³, C. Pütter³, M. Miller¹, A. Dechêne¹, S.R. Ross⁴, G. Gerken¹ and P. Hilgard¹,⁵

¹Department of Gastroenterology and Hepatology, ²Department of Nephrology, ³Institute for Medical Informatics, Biometry, and Epidemiology, ⁴Institute for Virology, University Hospital Essen, and ⁵Academic Teaching Hospital EVK, Muelheim a. d. Ruhr, Muelheim, Germany
Background: Among patients after renal transplantation (NTx), hepatitis C virus (HCV) infection is a risk factor for graft loss and patient death caused by hepatic decompensation. Also, HCV has been implicated in the pathogenesis of glomerular diseases in native and transplanted kidneys. Therefore, the aim of this retrospective cohort study was to determine the effects of the widely used calcineurin inhibitors (CNI) cyclosporine A (CsA) and tacrolimus (Tac) on hepatitis C virus replication, inflammatory activity, development of liver fibrosis, and long-term renal graft function. Subjects and methods: A cohort of 71 patients with HCV infection after kidney transplantation under immunosuppression with either CsA or Tac were analyzed for viral kinetics and serum transaminases. In addition, presence of liver fibrosis was detected by non-invasive measurements using the FibroScan. Graft function was determined biochemically. Patients with interferon therapy prior to transplantation were excluded from the study in order to avoid any impact of the antiviral therapy on outcomes. Results: In the early period after transplantation, hepatitis C viral load was lower in patients treated with Tac as compared to CsA. This effect became negligible 3 months after transplantation. However, hepatic inflammatory activity was reduced in the CsA-treated group. Extent of liver fibrosis was similar in both groups of HCV-infected patients as well as in a control group of non-HCV-infected patients after renal transplantation (NTx), respectively. Renal function and glomerular filtration rate, as calculated by the modification of diet in renal disease (MDRD) formula, were significantly better in patients treated with Tac. Conclusions: During long-term immunosuppression, the CNIs cyclosporine A versus tacrolimus showed no significant differences in HCV-infected patients after renal transplantation with respect to viral replication and development of liver fibrosis. However, function of the renal graft is significantly better preserved in patients receiving tacrolimus.Correspondence to:
P. Hilgard, MD
Associate Professor of Medicine
Academic Teaching Hospital EVK
Wertgasse 30
45468 Muelheim a. d. Ruhr, Germany
Email: philip.hilgard@evkmh.de

Abstract

Clinical Nephrology, Vol. 75 – No. 1/2011 (26-33)

The role of adiponectin in metabolic and vascular disease: a review

J. Cui, S. Panse and B. Falkner

Departments of Medicine and Pediatrics, Thomas Jefferson University, Philadelphia, PA, USA
Adiponectin is a protein secreted by adipose tissue. Unlike other adipocytokines produced by adipose tissue, adiponectin appears to have anti-inflammatory, anti-diabetic, and anti-atherogenic properties. Although secreted solely by adipose tissue, plasma levels of adiponectin are generally negatively related to total adipose mass; with higher plasma adiponectin levels in lean individuals and lower adiponectin levels in obese individuals. Plasma concentrations of adiponectin are lower in patients with insulin resistance compared to insulin sensitive patients; and lower in patients with diabetes compared to non-diabetics. A similar inverse relationship of plasma adiponectin level has been reported with hypertension (HTN), blood pressure level, and albuminuria. However, in chronic kidney disease (CKD) marked elevations in plasma adiponectin concentrations have been described. Plasma adiponectin levels are markedly elevated among patients with end-stage renal disease and are lower following kidney transplantation. Considering the inverse relationship of plasma adiponectin with renal function, the cardiovascular protective role of adiponectin in patients with CKD remains controversial. Further research on the distribution and function of different circulating fractions of adiponectin in patients with CKD will be needed in order to determine if adiponectin is a useful biomarker in patients with CKD.Correspondence to:
B. Falkner, MD
Department of Medicine
Division of Nephrology
Thomas Jefferson University
833 Chestnut Street, Suite 700
Philadelphia, PA 19107, USA
Email: Bonita.Falkner@jefferson.edu

Abstract

Clinical Nephrology, Vol. 75 – No. 1/2011 (34-48)

Fifty years of Balkan endemic nephropathy in Romania: some aspects of the endemic focus in the Mehedinti county

G. Gluhovschi¹, F. Margineanu², S. Velciov¹, C. Gluhovschi¹, F. Bob¹, L. Petrica¹, G. Bozdog¹, V. Trandafirescu¹ and M. Modalca²

¹Nephrology Department, University of Medicine and Pharmacy, Timisoara, and ²Dialysis Center Drobeta Turnu-Severin, Romania
Balkan endemic nephropathy (BEN) is a chronic tubulointerstitial nephritis seen primarily in countries in the Balkan Peninsula. The disease, which was first described in Romania 50 years ago, often manifests as a form of chronic nephritis that is also associated with upper urothelial cancers (UUC). This review summarizes the observations and studies performed in Romania regarding this disease during the last 50 years with particular emphasis on Mehedinti county. The paper analyzes current data on the epidemiology of the disease in this area, specifically in relation to the observations made in dialysis centers in the same area. It also discusses the diagnostic criteria of patients with BEN stemming from collaborations between specialists working in other countries affected by the disease. Moreover, the paper analyzes the main etiological factors suspected to play a role in BEN: aristolochic acid (the disease has many similarities to aristolochic nephropathy caused by Chinese herbs), mycotoxins, toxic substances from pliocene lignite, genetic factors, and viruses. Studies performed by Romanian authors are presented briefly in comparison to studies performed by other authors. Finally, given that BEN is an important health problem in the region, the relationship between BEN and UUC is further analyzed.Correspondence to:
Prof. Dr. G. Gluhovschi
Nephrology Department
University of Medicine and Pharmacy
Calea Aradului 8 Ap. 16
300088 Timisoara, Romania

Email: ggluhovschi@yahoo.com

Abstract

Clinical Nephrology, Vol. 75 – No. 1/2011 (49-58)

Relationship between insulin resistance and erythropoietin responsiveness in hemodialysis patients

M. Abe¹, K. Okada¹, M. Soma¹,² and K. Matsumoto¹

¹Division of Nephrology, Hypertension and Endocrinology, and ²Division of General Medicine, Department of Internal Medicine, Nihon University School of Medicine, Tokyo, Japan
Background: Insulin resistance is an independent predictor of cardiovascular mortality in hemodialysis (HD) patients. Inflammation plays an important role in insulin resistance, and adipocytokines, including tumor necrosis factor-alpha and leptin, can induce insulin resistance. However, data on insulin resistance and erythropoietin responsiveness in HD patients are lacking. Methods: We conducted a prospective, observational cohort study to clarify the relationship between insulin resistance and erythropoietin responsiveness in HD patients. Insulin resistance as assessed by the homeostasis model assessment for insulin resistance (HOMA-IR), levels of adiponectin and inflammatory cytokines, required erythropoietin (EPO) dose, and other metabolic parameters were measured in patients with (n = 52) and without diabetes (n = 55) over the course of 12 months. Results: The diabetes group had significantly higher serum leptin, high-sensitivity C-reactive protein, and interleukin-6 concentrations but lower serum adiponectin concentration. Average hemoglobin (Hb) levels during the 12-month study period were significantly lower in the diabetes group than in the non-diabetes group, and a higher dose of EPO was required in the diabetes group. There was a significant negative correlation between adiponectin and HOMA-IR, a significant positive correlation between EPO dose and HOMA-IR, and a significant negative correlation between EPO dose and adiponectin in the two groups. Insulin resistance as established by HOMA-IR and adiponectin was associated with EPO responsiveness in HD patients. HOMA-IR, Hb, and adiponectin levels were found to be independent predictors of EPO dose in HD patients with diabetes. Conclusion: Insulin resistance is associated with EPO responsiveness in HD patients. Patients in the diabetes group had a lower response to EPO than those in the non-diabetes group. For improvement in EPO response, insulin resistance may be a new target for treating HD patients.Correspondence to:
M. Abe, MD
Division of Nephrology
Hypertension and Endocrinology
Department of Internal Medicine
Nihon University School of Medicine
30-1, Oyaguchi Kami-chou, Itabashi-ku
Tokyo 173-8610, Japan
Email: mabe@med.nihon-u.ac.jp

Abstract

Clinical Nephrology, Vol. 75 – No. 1/2011 (59-62)

Biosimilar epoetin zeta in nephrology – a single-dialysis center experience

G. Lonnemann and E. Wrenger

Private Outpatient Clinic and Dialysis Centre, Langenhagen, Germany
Aim: An observational clinical study was performed to test the efficiency of the biosimilar product epoetin zeta to maintain stable hemoglobin levels in end-stage renal disease (ESRD) patients on intermittent high-flux hemodialysis. Patients and methods: Before the start of the study, 17 out of 18 patients were on various erythropoiesis-stimulating agents (ESA). After a run-in period of 2 months, all patients switched to epoetin zeta and were followed for 6 months. The initial weekly doses as well as the frequency of application per week were kept constant. To convert patients on darbepoetin (n = 12) to epoetin zeta, a factor of 1 : 200 was used. During the follow-up, hemoglobin levels, iron status, dialysis efficiency, body weight, and adverse events were monitored at least once a month. Results: Comparing time 0 (before the start of epoetin zeta) with the end of the study (6 months of epoetin zeta), no significant changes were observed: Hemoglobin 11.72 ± 0.64 g/dl versus 11.62 ± 0.70 g/dl (p = 0.64); weekly dose of ESA: 79.4 ± 57.7 IU/kg/week at start versus 91.8 ± 65.4 IU/kg/week at the end (p = 0.55). It is noteworthy that the frequency of application could be reduced to once a week or less with epoetin zeta in 66% of the 18 patients. After 6 months of epoetin zeta, 10 patients received 1 dose/week, and 2 patients received only 1 dose every 2 weeks. There were no significant changes in mean blood pressure, body weight and hemodialysis efficiency comparing the end with the start of the observation. No side effects attributable to the ESA-therapy have been observed. Conclusion: The biosimilar product epoetin zeta is safe in clinical practice and is effective and stable in the weekly dose as well as in the frequency of application. Biosimilars offer a welcome opportunity to reduce treatment costs of renal anemia.Correspondence to:
Prof. Dr. G. Lonnemann
Eickenhof 15
30851 Langenhagen, Germany
Email: Lonnemann@eickenhof-dialyse.de

Abstract

Clinical Nephrology, Vol. 75 – No. 1/2011 (63-69)

Pharmacokinetics and safety of multiple doses of daptomycin 6 mg/kg in noninfected adults undergoing hemodialysis or continuous ambulatory peritoneal dialysis

D.P. Benziger¹, P.E. Pertel², J. Donovan¹, S. Yankelev¹, R.J. Schwab³, S.K. Swan⁴ and C. Cannon⁴

¹Cubist Pharmaceuticals, Inc., Lexington, ²Novartis Institutes for Biomedical Research, Cambridge, MA, ³University of Nebraska Medical Center, Omaha, NE, and ⁴DaVita Clinical Research and Hennepin County Medical Center, Minneapolis, MN, USA
Aims: The purpose of this study was to characterize the pharmacokinetics and tolerability of daptomycin in subjects undergoing hemodialysis (HD) or continuous ambulatory peritoneal dialysis (CAPD). Method: 16 noninfected adults on stable dialysis regimens were enrolled. Daptomycin 6 mg/kg was administered after HD during a 48 h – 48 h – 72 h dialysis week or before a CAPD dwell time over a 48 h – 48 h – 48 h dialysis week. Pharmacokinetic parameters were described, and adverse events were monitored. Results: Daptomycin had mean half-lives in HD subjects of 28.0 and 35.9 h on Days 1 and 5, with corresponding values of 25.8 and 26.7 h in CAPD subjects. Steady state was reached by Day 5 in both groups. At steady state, HD subjects had a mean peak plasma concentration (C_max) of 81.6 µg/ml and a mean trough concentration of 15.3 µg/ml (on Day 8). In CAPD subjects, C_max was 93.9 µg/ml and the trough was 20.7 µg/ml (on Day 7). Adverse events were experienced by 71.4% and 66.7% of HD and CAPD subjects, respectively. Most of these were mild or moderate in intensity; however, 2 subjects experienced muscle spasms and mild creatine phosphokinase elevations although neither event was considered to be related to study drug. Conclusions: The pharmacokinetics of daptomycin 6 mg/kg support a dosing regimen of every 48 h in CAPD and thrice-weekly dosing in HD.Correspondence to:
D.P. Benziger, PhD
Cubist Pharmaceuticals, Inc.
65 Hayden Avenue
Lexington, MA 02421, USA
Email: david.benziger@cubist.com

Abstract

Clinical Nephrology, Vol. 75 – No. 1/2011 (70-73)

Unsuccessful application of taurolidine in the treatment of fungal peritonitis in peritoneal dialysis

M. Gallieni, G. Chiarelli, L. Olivi, M. Cozzolino and D. Cusi

Nephrology and Dialysis Unit, San Paolo Hospital, Dipartimento Medicina Chirurgia Odontoiatria, Facoltà di Medicina, Università degli Studi di Milano, Italy
Fungal peritonitis (FP) is a serious complication for peritoneal dialysis (PD) patients, determining hospitalization, technique failure, catheter loss and death. In the 2005 update, treatment recommendations for FP from the International Society of Peritoneal Dialysis (ISPD) advocate catheter removal immediately after fungi are identified by microscopy or culture. The availability of more eff ective medical treatments could therefore be of great importance. The aim of this report is to describe a case of a 43-year-old, diabetic, HIV positive PD patient with fluconazole resistant Candida peritonitis, who was treated with an i.p. taurolidine solution. Taurolidine is a non-antibiotic antimicrobial, with broad bactericidal and fungicidal properties. It has been used during surgery for lavage of the peritoneum in cases of peritonitis. Its mechanism of action is related to direct toxic action on micro-organisms, through a chemical reaction between active taurolidine derivatives and structures on the cell wall. Treatment failed because the patient had severe burning pain during i.p. administration of the drug, limiting its dose. PD catheter removal allowed complete recovery. It remains undetermined if, with different doses and methodology, taurolidine could be more effective in treating bacterial and/or fungal peritonitis. Currently, catheter removal remains the most effective therapy of fungal peritonitis.Correspondence to:
M. Gallieni, MD
Nephrology and Dialysis Unit
San Paolo Hospital
Dipartimento Medicina Chirurgia Odontoiatria
Facoltà di Medicina
Università degli Studi di Milano
Via di Rudinì, 8, 20142 Milano, Italy
Email: maurizio.gallieni@unimi.it

Abstract

Clinical Nephrology, Vol. 75 – No. 1/2011 (74-79)

Systemic non-amyloidotic fibril deposition disease: a probable variant form of fibrillary glomerulonephritis

J. Soma¹, K. Sato¹, I. Nakaya¹, M. Yahata¹, T. Sakuma² and H. Sato³

Departments of ¹Nephrology and ²Pathology, Iwate Prefectural Central Hospital, Morioka, and ³Department of Nephrology, Endocrinology and Hypertension, Tohoku University, Sendai, Japan
Fibrillary glomerulonephritis (FGN) is characterized by deposition of non-amyloidotic fibrillary material in glomeruli, and most patients with the disease show heavy proteinuria and hematuria, and progress into end-stage renal failure. We report a 62-year-old woman with FGN who showed mild proteinuria without hematuria and developed rapidly progressive renal failure requiring hemodialysis. Renal biopsy showed severe tubulointerstitial injury associated with non-amyloidotic fibrillary deposits in the tubular basement membrane, interstitium and vessel walls, in addition to glomeruli. The patient died from liver abscess 1 year after the introduction of hemodialysis. Postmortem examination showed the presence of non-amyloidotic fibrillary deposits arranged in tightly packed electron-dense and bundle-shaped structures in many organs. These findings suggest systemic non-amyloidotic fibril deposition in FGNCorrespondence to:
J. Soma, MD, PhD
Department of Nephrology
Iwate Prefectural Central Hospital
1-4-1 Ueda, Morioka 020-0066, Japan
Email: sjun@chuo-hp.jp

Abstract

Clinical Nephrology, Vol. 75 – No. 1/2010 (80-88)

An uncommon glomerular disease in an HIV patient: value of renal biopsy and review of the literature

C. Chen¹, K.D. Jhaveri⁴, C. Hartono²,⁵ and S.V. Seshan³

¹Department of Medicine, Tufts Medical Center, Boston, MA, ²Division of Nephrology and Hypertension and the ³Department of Pathology, New York Presbyterian Hospital-Weill Cornell Medical College, New York, ⁴Division of Nephrology, North Shore University Hospital, Manhasset, NY, and ⁵The Rogosin Institute, New York, NY, USA
Renal disease is not uncommon in those infected with HIV. The most common manifestation of HIV in the kidney is HIV-associated nephropathy (HIVAN). Other HIV- and non-HIV-related causes have been described in the literature. Immunotactoid glomerulonephritis (ITG) is a rare disorder found in 0.06% of renal biopsies characterized by organized tubular immune complex deposits, observed more often in Caucasians. ITG tends to occur in an older age group and in some patients has been associated with a hemopoietic malignancy. In this report, we describe a case of ITG occurring in an HIV-positive, hepatitis C (HCV)- and hepatitis B (HBV)-negative female, who presented with microscopic hematuria and proteinuria. A percutaneous kidney biopsy showed diffuse membranous glomerulopathy, with mild mesangial proliferation and segmental sclerosing lesions containing mainly IgG, Kappa- and C3-positive deposits. Electron microscopy revealed diffuse subepithelial tubular deposits diagnostic of ITG. Out of 5 reported HIV-positive cases and ITG in the literature, 3 were HCV+, 2 were Caucasian and 3 were African-American (AA) without detectable hematologic malignancy. We report another case of ITG in an HCV- and HBV-negative, AA female.Correspondence to:
K.D. Jhaveri, MD
North Shore University Medical Center
Great Neck, NY 11021, USA
Email: kjhaveri@nshs.edu

Abstract

Acute pancreatitis in a 2-year-old girl on peritoneal dialysis and using icodextrin solution

S. Fujinaga, N. Nishizaki, D. Hirano, H. Kanai, M. Suzuki, Y. Ohtomo, K. Kaneko and T. Shimizu

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Volume 75, No. 1/2011(January)