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Abstract

Clinical Nephrology, Vol. 74 – No. 2/2010 (83-90)

Effect of parathyroid hormone and teriparatide on immune function of human adherent and non-adherent leukocytes

M. Castellanos¹, E. Jung², S.Y. Park³, G. Schuller-Levis², M. Odaimi⁴, S. Elsayegh⁵, M. Kleiner⁵, R. Elsoueidi⁴, N. Shtaynberg⁵ and E. Park²

¹Medical Research, Department of Medicine, Staten Island University Hospital, ²Laboratory of Cellular Immunology, Department of Developmental Neurobiology, NYS Institute for Basic Research in Developmental Disabilities, Staten Island, NY, USA, ³College of Veterinary Medicine, Konkuk University, Seoul, Korea, ⁴Division of Hematology/Oncology, and ⁵Division of Nephrology, Department of Medicine, Staten Island University Hospital, Staten Island, NY, USA
Clinical data indicate that patients with hyperparathyroidism due to chronic kidney disease have abnormal immune function. We evaluated the direct effect of parathyroid hormone (PTH) and two 1-34 peptide fragments of PTH on immune function in activated leukocytes from healthy donors. IL-6 and IL-8 were measured from supernatants from phytohemagglutinin-activated non-adherent and lipopolysaccharide-activated adherent leukocytes in the presence of PTH and the two peptides using ELISA. Data showed no significant change in IL-6 and IL-8 production using PTH (0.1 – 0.8 µM) or two peptides (0.2 – 1.6 µM). Lymphocyte proliferation using ³H-thymidine was not inhibited with 0.1 – 0.4 µM of PTH. However, lymphocyte proliferation was significantly inhibited at the highest dose (0.8 µM) of PTH. There was no effect of two peptides on lymphocyte proliferation. Except for inhibition of lymphocyte proliferation at the highest dose of PTH tested, our data demonstrate no direct effect of PTH and two peptide fragment on immune function.Correspondence to:
M.R. Castellanos, MD
Clinical Director of Research
Department of Medicine
475 Seaview Avenue
Staten Island, NY 10305, USA
Email: mario_castellanos@siuh.edu

Abstract

Clinical Nephrology, Vol. 74 – No. 2/2010 (91-96)

Serum alkaline phosphatase and mortality in hemodialysis patients

S. Beddhu¹, ², B. Baird², X. Ma², A.K. Cheung¹,² and T. Greene¹,²

¹Veterans Affairs Salt Lake City Healthcare System, and ²Department of Medicine, University of Utah, Salt Lake City, UT, USA
Background: Alkaline phosphatase is typically considered as an innocent by-stander, but emerging data suggest that alkaline phosphatase might play a pathogenic role in vascular calcification and thus contribute to increased mortality in hemodialysis patients. Study design: Longitudinal analyses of the existing HEMO Study database. Setting and participants: 1,827 HEMO Study participants. Predictor: Serum alkaline phosphatase level. Outcome and measurements: All-cause and cardiovascular mortality. Results: Based on the median serum alkaline phosphatase of 97 IU/l, participants were divided into low (< 97 IU/l) and high (>= 97 IU/l) serum alkaline phosphatase groups. The lower serum alkaline phosphatase group was associated with older age, male gender, non-black race and shorter dialysis years as well as higher serum calcium, higher serum calcium-phosphorus product and lower parathyroid hormone levels. Mean serum liver enzyme values were in the normal range in both groups, but the high alkaline phosphatase group had slightly higher values. In a multivariate time-dependent Cox model using baseline and follow-up values of serum alkaline phosphatase levels, adjusted for demographics, HEMO Study groups, comorbidity, bone metabolism parameters and liver enzymes, each doubling of serum alkaline phosphatase was significantly associated with increased hazard of all-cause (hazard ratio 1.44, 95% CI 1.30 – 1.59) and cardiovascular mortality (hazard ratio 1.35, 95% CI 1.16 – 1.57). Limitations: Nonstandardized measurements of alkaline phosphatase. Conclusions: Serum alkaline phosphatase is associated with increased mortality in hemodialysis patients, independent of bone metabolism parameters and liver enzymes. Alkaline phosphatase might be a potential therapeutic target in hemodialysis patients.Correspondence to:
S. Beddhu, MD
Associate Professor of Medicine
85 North Medical Drive East, Room 201
Salt Lake City, UT 84112, USA
Email: Srinivasan.beddhu@hsc.utah.edu

Abstract

Clinical Nephrology, Vol. 74 – No. 2/2010 (97-105)

Treatment of growth failure with growth hormone in children with chronic kidney disease: an open-label long-term study

D. Müller-Wiefel¹, H. Frisch², T. Tulassay³, L. Bell⁴ and Z. Zadik⁵

¹Paediatric Nephrology, University Medical Center, Hamburg, Germany, ²Universitäts-Kinderklinik, Vienna, Austria, ³Semmelweis University Medical School, Budapest, Hungary, ⁴Montreal Children’s Hospital, Montreal, Canada, and ⁵Kaplan Medical Center, Rehovot, Israel
Aims: To assess long-term efficacy and safety of recombinant human growth hormone (GH) in children with chronic kidney disease (CKD). Methods: An open-label, international, multicenter study. Children with CKD and growth failure received GH (0.35 mg/kg/week). The primary efficacy endpoint was a significant change in height velocity (HV) and height standard deviation score (SDS) versus baseline after 12 months of treatment, extended to 24 months, then to 5 years. Results: In total, 81 patients enrolled (CKD Stage 4 – 5 = 37, on dialysis = 27, post-transplant = 17). After 12 and 24 months of treatment, increases were seen in mean (SD) HV (4.6 (3.1) to 9.0 (3.6) cm/year and 4.5 (3.3) to 7.5 (2.9) cm/year, respectively; both p < 0.001), mean (SD) height SDS (–3.7 (1.7) to –3.0 (1.7) and –3.6 (1.5) to –2.5 (1.5), respectively; both p < 0.001) and mean (SD) HV SDS (–2.4 (2.5) to 3.8 (4.5) and –2.4 (2.2) to 1.1 (3.8), respectively; both p < 0.001). A normal height SDS was seen in 1% of children at baseline, 17% after 12 months and 43% after 24 months of treatment. Improvements were similar across CKD subgroups with the greatest improvements in CKD Stage 4 – 5. Among 31 patients who completed about 5 years of treatment, four reached final height. There was no undue bone age acceleration and no deterioration of kidney function. Ten adverse events were related to GH treatment. Conclusions: In this long-term study, GH treatment was associated with significant improvements in growth and height in children with CKD and growth failure, and was well tolerated.Correspondence to:
Prof. Dr. D.E. Müller-Wiefel
Paediatric Nephrology
University Medical Center
Hamburg Eppendorf
Martinistr. 52
20246 Hamburg, Germany
Email: muellerw@uke.uni-hamburg.de

Abstract

Clinical Nephrology, Vol. 74 – No. 2/2010 (106-112)

True vasculitis in lupus nephritis

A.A. Abdellatif¹,², S. Waris¹, A. Lakhani¹, H. Kadikoy¹, W. Haque¹ and L.D. Truong¹,², ³,⁴

Departments of ¹Medicine, ²Division of Nephrology, Baylor College of Medicine, Departments of ³Pathology and ⁴Division of Nephropathology, The Methodist Hospital, Houston, TX, USA
Vascular lesions are encountered frequently in renal biopsy specimens of patients with systemic lupus erythematosus (SLE) and can present in a variety of morphologic forms. True renal lupus vasculitis (TRLV) is one of the rare vascular lesions associated with lupus nephritis that has been infrequently reported in the medical literature. The primary focus on glomerular pathology and collective classification of the vascular lesions under lupus vasculopathy is one of the reasons why this form of inflammatory vasculitis has been under-recognized as a separate disease entity. Here we have comprehensively reviewed the literature on renal vascular involvement in SLE for a better understanding of the epidemiology, morphologic features, pathogenesis, clinical course and treatment of TRLV. It can be morphologically differentiated from other forms of renal vascular lesions in lupus nephritis, i.e. arteriosclerosis, uncomplicated vascular immune deposits, non-inflammatory necrotizing vasculopathy, and thrombotic microangiopathy. Despite close similarities with antineutrophil cytoplasmic autoantibody associated vasculitis (AASV), there are certain morphological differences that warrant a thorough investigation of the possible pauci-immune mechanism of pathogenesis. The vasculitis follows a severe clinical course in general with rapid progression to renal failure, although favorable outcomes have been reported in certain cases. The standard use of steroids and cytotoxic drugs has yielded variable results in the treatment of TRLV. Current treatment modalities being used in lupus nephritis and AASV have been compared in this article with focus on drugs acting on the inflammatory cells implicated in TRLV pathogenesis.Correspondence to:
A.A. Abdellatif, MD, FASN
Department of Medicine,
Baylor College of Medicine
One Baylor Plaza, BCM 620
Houston, TX 77030, USA
Email: abdula@bcm.edu

Abstract

Clinical Nephrology, Vol. 74 – No. 2/2010 (113-122)

Renal artery revascularization in patients with atherosclerotic renal artery stenosis and impaired renal function: conservative management versus renal artery stenting

L.E. Dichtel¹,²*, DF. Gurevich¹,²**, B. Rifkin³, P. Varma⁴,⁵, J. Concato¹,²,⁶ and A.J. Peixoto¹,²,⁷

¹Medical Service, VA Connecticut Healthcare System, West Haven, CT, ²Department of Medicine, Yale University School of Medicine, New Haven, CT, ³Nephrology Department, Hattiesburg Clinic, Hattiesburg, MS, ⁴Radiology Service, VA Connecticut Healthcare System, West Haven, CT, ⁵Department of Diagnostic Imaging, Yale University School of Medicine, New Haven, CT, and ⁶VACT Clinical Epidemiology Research Center, West Haven, CT, USA
Background: The impact of percutaneous renal artery angioplasty and stenting (PTRAS) for treatment of atherosclerotic renal artery stenosis (ARAS) is not fully understood, especially in patients with chronic kidney disease (CKD). The goal of this study was to compare renal outcomes in patients treated with PTRAS with those managed conservatively. Methods: Retrospective cohort study of 118 prevalent patients with significant ARAS and moderate-to-severe CKD who were treated medically (n = 71) or with PTRAS (n = 47). The primary endpoint was change in renal function over the first year after diagnosis/treatment. Results: Average age was 73 ± 8 years, baseline glomerular filtration rate was 37 ± 15 ml/min/1.73 m², and average follow-up was 34 months. Baseline characteristics were similar between the two groups, with the exception of higher diastolic blood pressure in the PTRAS group (75 versus 70 mmHg, p = 0.028). There were no significant differences between the two groups during follow-up. The decline in glomerular filtration rate was similar in both groups (–1.6 ml/min/1.73 m² in the medical group versus –1.4 ml/min/1.73 m² in the PTRAS group, p = 0.938). Multivariate models did not indicate an association between treatment modality and changes in renal function or rates of ESRD or death. Conclusion: In patients with advanced kidney disease, medical therapy and renal artery stenting appear comparable in stabilizing renal function for ARAS.Correspondence to:
A.J. Peixoto, MD
Medical Service – 111
950 Campbell Avenue
West Haven, CT 06516, USA
Email: aldo.peixoto@yale.edu

Abstract

Clinical Nephrology, Vol. 74 – No. 2/2010 (123-131)

Association of immune cell function assay with protocol biopsy findings and viral infections in well matched kidney transplant recipients

I. Helanterä and P. Koskinen

Department of Medicine, Division of Nephrology, Helsinki University Central Hospital and University of Helsinki, Helsinki, Finland
Background: Cylex^® Immune Cell Function Assay (ICFA) is in clinical use, but little is known about its association with screening of viral infections or findings in protocol biopsies. Patients and methods: We analyzed ICFA in our well-matched kidney transplant population. Helsinki University Hospital patients who received a kidney transplant after July 2007 were analyzed. Patients with at least 6 months follow-up and ICFA measured together with the screening for cytomegalovirus (CMV), or polyomaviruses from urine or plasma, or patients with a protocol biopsy at 6 or 12 months taken at the time of the ICFA were included (n = 27). Immunosuppression was usually implemented with mycophenolate mofetil (MMF), steroids and cyclosporine A (CyA). Biopsies were analyzed with chronic allograft damage index (CADI). Results: Mean immune response in 61 samples was 368 ± 179 ATP ng/ml. Immune response was lower during BK virus (BKV) or CMV viremia compared to no viremia (p = 0.009 and p = 0.017), and no viremia was seen if immune response was > 380. BK or JC viruria was not associated with low immune response. Immune responses did not differ between patients with high or low CADI scores or between patients with immune activation or no immune activation in biopsies. Immune response in our population was higher than previously reported without increased risk of rejections. ICFA correlated with viremia but not with findings in protocol biopsies. Conclusion: The optimal immune response in our population needs further studies.Correspondence to:
I. Helanterä, MD, PhD
Department of Medicine
Division of Nephrology
Helsinki University Hospital
Kasarmikatu 11-13
PO Box 263
00029 HUS, Helsinki, Finland
Email: ilkka.helantera@helsinki.fi

Abstract

Clinical Nephrology, Vol. 74 – No. 2/2010 (132-140)

A comparison of plasma cystatin C and plasma creatinine for the screening of renal function in lithium-treated patients

C.L. Olsson¹, B. Rippe² and H. Bendz³

¹Department of Psychiatry, Malmö University Hospital, Malmö, ²Department of Nephrology, and ³Department of Psychiatry, Lund University Hospital, Lund, Sweden
Background: Renal insufficiency is a serious complication of lithium treatment. Therefore, regular monitoring of plasma (P) creatinine is always part of lithium treatment safety routines. Recently P-cystatin C-estimated glomerular filtration rate (cystatin C-eGFR) had been launched as a preferable alternative to P-creatinine. Aims: To find out which of the two alternatives to prefer in the safety routines for lithium-treated patients. Material: All 201 patients on lithium treatment at the Department of Psychiatry in Lund, Sweden. Methods: During 14 months P-cystatin C was included in the safety routines besides routine P-creatinine every 4 months. At the end of the study period, 182 patients were eligible for analysis. With iohexol clearance as reference for GFR (performed in 111/182 patients) we calculated positive and negative predictive values (PPV, NPV) for P-creatinine and for creatinine-eGFR and cystatin C-eGFR, obtained by prediction equations. We also calculated the agreement between the measures of GFR (including repeatability). Results: PPV for cystatin C-eGFR (65%) was better than for creatinine-eGFR (48%). Combining the two resulted in a PPV of 56% and marginally increased NPV to 95%. The average of cystatin C-eGFR and creatinine-eGFR yielded PPV 67% and NPV 92%. The agreement between creatinine-eGFR and GFR was better than the agreement between cystatin C-eGFR and GFR, but both were clinically unacceptable. The repeatability of P-creatinine was acceptable for psychiatric purposes. The repeatability of cystatin C-eGFR was inferior to that of P-creatinine. Conclusion: Our results do not justify replacing P-creatinine by cystatin C-eGFR in the lithium treatment safety routines.Correspondence to:
Dr. H. Bendz
Department of Psychiatry
University Hospital of Lund
S-211 85 Lund, Sweden
Email: hans.bendz@med.lu.se

Abstract

Clinical Nephrology, Vol. 74 – No. 2/2010 (141-143)

Community-acquired Clostridium difficile-associated diarrhea in a patient on chronic peritoneal dialysis

M. Seo, N. Takahashi, T. Morita, S. Morimoto and T. Iwasaka

Second Department of Internal Medicine, Kansai Medical University, Hirakata, Osaka, Japan
A 66-year-old woman on chronic peritoneal dialysis was admitted because of intermittent diarrhea and abdominal pain, and anorexia for 1 month. She had not been given antibiotics nor hospitalized for at least 6 months prior to the onset of symptoms. Clostridium difficile and its toxin were detected in the stool and Clostridium difficile-associated diarrhea (CDAD) was diagnosed. Colonoscopic examination revealed pseudomembrane formation and colitis in the whole colon. Clostridium difficile and its toxin became negative 12 days after vancomycin administration. Thus, clinical suspicion to CDAD is important in dialysis patients presenting with abdominal symptoms even if it is apparently community-acquired with no history of antibiotic use and hospitalization.Correspondence to:
N. Takahashi, MD
Second Department of Internal Medicine
Kansai Medical University
2-3-1 Shinmachi, Hirakata
Osaka 573-1191, Japan
Email: takahasn@hirakata.kmu.ac.jp

Abstract

Cerebral venous sinus thrombosis in adult nephrotic syndrome

H. Xu, K. Chen, D. Lin, L. Dai, H. Chen and Z. Xu

Department of Nephrology, The Affiliated Hospital of Putian College and Fujian Medical University’s Teaching Hospital, Putian, Fujian, PR China
Cerebral venous sinus thrombosis (CVST) is an uncommon condition marked by clotting of blood in cerebral venous, dural sinuses, or cortical veins. It is rather rare that CVST is reported as a complication in nephrotic syndrome, which could have potentially fatal consequences. Here we report a young man with CVST as a complication of nephrotic syndrome, who was diagnosed with MRV and treated with local thrombolysis. We also reviewed 10 reported cases of CVST in adult nephrotic syndrome in the literature together with our current case. CVST in nephrotic syndrome appears to occur mostly in the 20 to 45-year-old adults with poorly controlled nephrosis or initial onset of nephrotic syndrome. Due to its various and nonspecific neurological presentations, early diagnosis with CT, MRI and/or MRV is essential for early intervention. Anticoagulation is the current treatment recommendation based on the available evidence.Correspondence to:
H. Xu, MD, MS
Department of Nephrology
The Affiliated Hospital of Putian College
181 Meiyuan Road
Putian, Fujian 351100, PR China
Email: haishanxu@hotmail.com

Abstract

Clinical Nephrology, Vol. 74 – No. 2/2010 (150-153)

HLA haplotype in a patient with systemic lupus erythematosus triggered by hepatitis B vaccine

D. Santoro¹, G. Vita², R. Vita³, A. Mallamace¹, V. Savica¹, G. Bellinghieri¹, S. Benvenga⁴ and S. Gangemi⁵

¹Unit of Nephrology and Dialysis, Department of Clinical and Experimental Medicine, ²Unit of Tissue Typing, Department of Pathology and Experimental Microbiology, ³Section of Endocrinology, Department of Clinical and Experimental Medicine, ⁴Section of Endocrinology, Department of Clinical and Experimental Medicine, Program of Molecular and Clinical Endocrinology and ⁵School and Division of Allergy and Clinical Immunology, Department of Human Pathology, AOU Policlinico G. Martino, Messina, Italy
Aim: Find an association between hepatitis B vaccine-related systemic lupus erythematosus and HLA. Material: A 27-year-old woman who developed a lupus nephritis after the administration of hepatitis B vaccine. Methods: We studied HLA antigen expression on lymphocytes and genomic haplotype. Class I-II HLA antigen typing was performed by the microlymphocytotoxicity test with the standard NIH method, and Class I-II HLA allele typing by polymerase chain reaction, using single-strand oligonucleotide dot-blot kits. Results: The serological haplotype was HLA A24/25, B18 (Bw6)/–, C–/–, DQ7/–, DR11(5)/52. The genomic haplotype was A*2403/2504, B*1825/1825, C*1207/ 1207, DRB1*1102/1132, DRB3*0202/0202, DQA1*0505/0505, DQB1*0301/0301. Then we sought for analogies with haplotypes known to be related to other systemic AID. Since we have found HLA alleles typical both of systemic lupus erythematosus and Sjogren’s syndrome, the persistence of ENA-SSA positivity was highly suspicious for a possible overlap syndrome. Conclusions: Hepatitis B vaccine can potentially trigger both the onset or the exacerbations of several autoimmune disorders, including systemic lupus erythematosus, by reduced immune complex clearance or molecular mimicry. This study represents the first report on the association between hepatitis B vaccine related systemic lupus erythematosus and HLA. Probably autoimmune reactions triggered by vaccines occur only in predisposed subjects, in which antigen presentation influenced by HLA haplotypes leads to the autoimmune cascade. More studies are needed to corroborate our hypothesis. They could disclose new pathways in the field of prevention.Correspondence to:
S. Gangemi
Padiglione H, 2 piano
AOU Policlinico G. Martino,
98125 Messina, Italy
Email: sebastiano.gangemi@unime.it

Abstract

Clinical Nephrology, Vol. 74 – No. 2/2010 (154-158)

Reversible posterior leukoencephalopathy syndrome in a patient with severe uremic encephalopathy

N. Tatsumoto¹, K. Fujisaki¹, H. Nagae¹, A. Ono-Fujisaki¹, N. Kura-Nakamura¹, M. Taniguchi¹, K. Masutani¹, K. Tsuruya² and M. Iida¹

¹Department of Medicine and Clinical Science, and ²Department of Integrated Therapy for Chronic Kidney Disease, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan
A 59-year-old male presented at our hospital with disturbance of consciousness. He had severe neurological disturbances associated with uremia caused by severe renal insufficiency. Cranial computed tomography (CT) was normal on admission. FLAIR-weighted MRI showed increased signal intensities bilaterally in the cortical and subcortical areas of the occipital lobe. Repeated hemodialysis resulted in improvement of the clinical symptoms and blood chemistry, and normalization of the MRI findings. Although the patient was discharged without neurological deficit, he had to be maintained on regular intermittent hemodialysis due to persistent renal failure. These reversible neuroradiological abnormalities may have been caused by reversible brain edema, but other pathoetiological factors should be also considered, such as abnormalities of cerebral metabolism and effects of uremic toxins.Correspondence to:
K. Tsuruya, MD, PhD
Department of Integrated Therapy for Chronic Kidney Disease
Graduate School of Medical Sciences
Kyushu University
Maidashi 3-1-1, Higashi-ku
Fukuoka 812-8582, Japan
Email: tsuruya@intmed2.med.kyushu-u.ac.jp

Abstract

Clinical Nephrology, Vol. 74 – No. 2/2010 (159-163)

A case of acute phosphate nephropathy in a patient with nephrotic syndrome and decreased serum fetuin-A

S.H. Han¹,²*, J.E. Lee¹*, S.H. Lee¹, J.J. Li³, S.W. Hong⁴, D.S. Han¹ and S.-W. Kang¹

¹Department of Internal Medicine, College of Medicine, Brain Korea ²¹ Project for Medical Science, Yonsei University, Seoul, ²Department of Internal Medicine, NHIC Ilsan Hospital, Goyangshi, Gyeonggi-do, Korea, ³Department of Internal Medicine, Nephrology and Dialysis Unit, the Affiliated Hospital, YanBian University Medical College, JiLin, China, and ⁴Department of Pathology, Yonsei University College of Medicine, Seoul, Korea

*These two authors contributed equally to this paper.
We report a case of APN after OSP use in a patient with nephrotic syndrome (NS). Renal biopsy revealed minimal change disease with multifocal calcium phosphate deposits within the tubules and in the interstitium. The serum level of fetuin-A, a systemic calcification inhibitor, was low during severely proteinuric state but normalized after remission of NS. To verify whether fetuin-A levels are low in NS patients, serum fetuin-A levels were determined in 10 patients with NS and 10 with asymptomatic microscopic hematuria (H). The mean serum fetuin-A levels were significantly lower in the NS group compared to the H group (p < 0.01). This finding suggests that a lower serum fetuin-A level may be associated with APN after OSP use in patients with NS, thus careful attention should be paid when colonoscopy using OSP is scheduled in this population.Correspondence to:
S.-W. Kang, MD, PhD
Department of Internal Medicine
Yonsei University College of Medicine
134 Shinchon-Dong
Seodaemoon-Gu, Seoul, 120-752, Korea
Email: kswkidney@yumc.yonsei.ac.kr

Abstract

Double synchronous primary renal cell carcinoma with different histotypes

T.H. Lee, W. Kim, S. Lee, K.P. Kang, Y.B. Jeong, M.J. Kang, S.G. Rho and S.K. Park

Abstract

Comment on “Minimal change nephrotic syndrome due to occupational mercury vapor inhalation”

M.J. Al Habbal

Abstract

Dr. Campbell’s response to: Comment on “Minimal change nephrotic syndrome due to occupational mercury vapor inhalation” from M.J. Al Habbal

G. Campbell

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Volume 74, No. 2/2010(August)