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Abstract

Clinical Nephrology, Vol. 86 – No. 5/2016 (287-289)

Successful return to peritoneal dialysis after a case of relapsing Sphingomonas paucimobilis peritonitis 

Jonathan Owen, Vaughan Washco, Efrain Reisin 

Section of Nephrology and Hypertension, Department of Medicine, Louisiana State University Health Sciences Center, New Orleans, LA, USA
Sphingomonas paucimobilis is an uncommon source of peritonitis in patients undergoing peritoneal dialysis (PD). Although only a small number of cases have been reported, treatment failure rate is extremely high, with removal of the peritoneal dialysis catheter noted in ~ 50% of reported cases. The potential damage to the peritoneal membrane from peritonitis with this organism and the ability to return to PD after infection is unknown. We report a unique case in which a patient was able to successfully return to PD after relapsing Sphingomonas paucimobilis peritonitis, without apparent effects to dialysis clearance or ultrafiltration. Correspondence to:
Jonathan Owen, MD LSUHSC New Orleans
Department of Medicine
Section of Nephrology and Hypertension
Room 330A,  1542 Tulane Ave,  New Orleans, LA 70112, USA 
Email: [email protected]

Abstract

Clinical Nephrology, Vol. 86 – No. 3/2016 (125-131)

Relationship between resistin and mortality in maintenance hemodialysis patients 

Po-Jui Chi¹#⁴, Hung-Hsiang Liou²#³, Bang-Gee Hsu⁴#⁵, Jen Pi Tasi¹#⁴ 

¹Division of Nephrology, Department of Medicine, Dalin Tzuchi General Hospital, Chiayi County, ²Division of Nephrology, Department of Medicine, Hsin-Jen Hospital, ³Dialysis Center, Hsin-Ren Clinics, New Taipei City, ⁴School of Medicine, Tzu Chi University, Hualien, and ⁵Division of Nephrology, Buddist Tzu Chi General Hospital, Hualien, Taiwan
Aims: Determine the relationship of serum resistin level with outcome in maintenance hemodialysis (HD) patients. Materials and methods: This 49-month prospective study enrolled 101 HD patients and examined their clinical and demographic characteristics. Results: 23 of the 87 patients in the cohort died. Survivors were younger, had higher body mass index, diastolic blood pressure, and serum levels of albumin, creatinine, potassium, and phosphate, and lower serum levels of resistin. Receiver operating characteristic (ROC) curve analysis indicated the optimal cut-off value of resistin for prediction of mortality was 127.4 ng/mL (area under the curve (AUC) = 0.667, p = 0.01). Cox proportional-hazards regression analysis indicated that advanced age (p < 0.001) and resistin level above 127.4 ng/mL (p = 0.004) were associated with increased mortality risk. Albumin (p = 0.048), creatinine (p = 0.014), potassium (p = 0.023), calcium (p = 0.021), and phosphate (p = 0.001) were associated with decreased mortality risk. Multivariate regression analysis indicated that advanced age (adjusted hazard ratio (aHR) = 1.11, p < 0.0001) and elevated resistin concentration (aHR = 2.442, p = 0.0387) increased the risk for mortality. Conclusions: Advanced age and serum resistin concentration above 127.4 ng/mL are independent risk factors for mortality in patients undergoing maintenance HD. Correspondence to:
Dr. Tsai Jen Pi
Division of Nephrology, Department of Medicine
Dalin Tzuchi General Hospital
NO.2, Minsheng Rd., Dalin, Township,
Chiayi County, 622, Taiwan
Email: [email protected]

Abstract

International Journal of Clinical Pharmacology and Therapeutics, Vol. 54 – No. 10/2016 (743-749)

Prevalence and type of antidepressant therapy used by German general practitioners to treat female patients with osteoporosis 

Julia Drosselmeyer¹, Michael Rapp², Karel Kostev³ 

¹Fresenius University of Applied Sciences, Idstein, ²Department of Social and Preventive Medicine, University of Potsdam, Potsdam, and ³IMS Health, Frankfurt am Main, Germany
Objective: To estimate the prevalence and type of antidepressant medication prescribed by German primary care physicians for patients with depression and osteoporosis. Methods: This study was a retrospective database analysis conducted in Germany utilizing the Disease Analyzer^® Database (IMS Health, Germany). The study population included 3,488 female osteoporosis patients aged between 40 and 90 years recruited from 1,179 general practitioner practices and who were initially diagnosed with depression during the index period (January 2004 to December 2013). Follow-up lasted up to 12 months and was completed in August 2015. Also included in this study were 3,488 nonosteoporosis controls who were matched (1 : 1) to osteoporosis cases on the basis of age, health insurance coverage, severity of depression, and physician carrying out the diagnosis. Results: After 12 months of follow-up, 30.1% of osteoporosis and 29.9% of nonosteoporosis patients with mild depression (p = 0.783), 52.4% of osteoporosis and 48.0% of non-osteoporosis patients with moderate depression (p = 0.003), and 39.4% of osteoporosis and 35.1% of nonosteoporosis patients with severe depression (p = 0.147) were being treated with antidepressants. Osteoporosis patients with moderate depression had a higher chance of being prescribed antidepressant therapy at the initial diagnosis (hazard ratio (HR): 1.12, p = 0.014). No differences were found between osteoporosis and nonosteoporosis patients regarding the proportion of patients receiving selective serotonin reuptake inhibitors (SSRI)/serotonin-noradrenaline reuptake inhibitors (SNRI), tricyclic antidepressant (TCA), or other antidepressants. Osteoporosis patients were more often referred to hospitals or psychiatrists for consultation. Conclusion: Osteoporosis patients are more often treated initially with antidepressants than non-osteoporosis patients, especially within the groups of patients with moderate or severe depression. TCA was the most frequently used antidepressant therapy class on initial diagnosis in both patient groups. Osteoporosis patients receive referrals to hospitals or psychiatrists more often than patients without osteoporosis. Correspondence to:
Prof. Dr. Karel Kostev
Senior Research Adviser
IMS Health – Epidemiology
Darmstäder Landstraße 108
60598 Frankfurt am Main, Germany
Email: [email protected]

Abstract

International Journal of Clinical Pharmacology and Therapeutics, Vol. 54 – No. 9/2016 (716-718)

Amoxicillin-induced aseptic meningitis: case report and review of published cases 

Viktorija Erdeljić Turk¹, Iveta Šimić¹,², Ksenija Makar-Aušperger¹, Matea Radačić-Aumiler¹ 

¹Division of Clinical Pharmacology, Department of Medicine, University Hospital Zagreb and ²Medical School, University of Zagreb, Zagreb, Croatia
Objective: Amoxicillin-induced aseptic meningitis (AIAM) is an extremely rare adverse reaction with only 12 reported cases. The term aseptic meningitis refers to patients who have clinical and laboratory evidence for meningeal inflammation with negative routine bacterial cultures. Since the exact pathogenesis is still unknown and clinical signs and cerebrospinalfluid (CSF) findings vary greatly, AIAM is usually a diagnosis of exclusion. Case summary: We report a clinical case of a patient referred to the clinical pharmacology outpatient clinic for consultation on suspected recurrent AIAM and a review of published cases. Conclusions: This report adds to the evidence-base of AIAM and emphasizes the importance of taking a thorough medication history in individuals with suspected meningitis. Considering the wide utilization of amoxicillin, it is important that healthcare providers are aware of AIAM. Correspondence to:
Viktorija Erdeljić Turk, MD, PhD
Department of Clinical Pharmacology
Department of Medicine
University Hospital Zagreb
Kišpaticeva 12, 10 000 Zagreb, Croatia
Email: [email protected]

Abstract

International Journal of Clinical Pharmacology and Therapeutics, Vol. 54 – No. 11/2016 (835-840)

Persistence with antipsychotics in dementia patients in Germany 

Anke Booker¹, Louis Jacob², Jens Bohlken³, Michael Rapp⁴, Karel Kostev¹ 

¹IMS Health, Epidemiology, Frankfurt, Germany, ²Department of Biology, Ecole Normale Supérieure de Lyon, Lyon, France, ³Psychiatric Practice Bohlken, Berlin, and ⁴Department of Social and Preventive Medicine, University of Potsdam, Potsdam, Germany
Background/Aims: To analyze the duration of treatment with antipsychotics in German dementia patients. Methods: This study included patients aged 60 years and over with dementia who received a first-time antipsychotic prescription by psychiatrists between 2009 and 2013. The main outcome measure was the treatment rate for more than 6 months following the index date. Results: A total of 12,979 patients with dementia (mean age 82 years, 52.1% living in nursing homes) were included. After 2 years of follow-up, 54.8%, 57.2%, 61.1%, and 65.4% of patients aged 60 – 69, 70 – 79, 80 – 89, and 90 – 99 years, respectively, received antipsychotic prescriptions. 63.9% of subjects living in nursing homes and 55.0% of subjects living at home also continued their treatment (p-value < 0.001). Conclusion: The percentage of dementia patients treated with antipsychotics is very high. Correspondence to:
Prof. Dr. rer. med. Karel Kostev
Epidemiology, Real World Evidence Solutions
IMS HEALTH GmbH & Co. OHG
Darmstädter Landstraße 108
60598 Frankfurt am Main, Germany 
Email: [email protected]

Abstract

International Journal of Clinical Pharmacology and Therapeutics, Vol. 55 – No. 3/2017 (275-285)

Meperidine-induced QTc-interval prolongation: prevalence, risk factors, and correlation to plasma drug and metabolite concentrations 

Guillermo Alberto Keller¹,², María Cecilia Villa Etchegoyen¹, Nicolás Fernández³, Nancy Mónica Olivera³, Patricia Noemi Quiroga³, Roberto Alejandro Diez¹, and Guillermo Di Girolamo¹ 

¹Drug Surveillance & Safety Center, Department of Pharmacology, School of Medicine, University of Buenos Aires, ²Emergency Department, Hospital General de Agudos Donación Francisco J. Santojanni, and ³Analytical Toxicology Advisory Centre (CENATOXA), Chair of Toxicology and Legal Chemistry, School of Pharmacy & Biochemistry, University of Buenos Aires, Buenos Aires, Argentina
A prolongation of the QTc-interval has been described for several opioids, including pethidine (meperidine). Objective: To evaluate in the clinical setting the frequency and risk factors associated with the QT-interval prolongation induced by meperidine. Research design and methods: We recruited patients requiring meperidine administration and recorded their medical history and comorbidities predisposing to QT-interval prolongation. Ionograms and electrocardiograms (ECGs) were performed at baseline and during treatment; QT was corrected using the Bazzet, Fridericia, Framinghan, and Hogdes formulas. We measured meperidine and normeperidine by gas chromatography. Values are expressed as mean ± SD (range). Results: 58 patients were studied (43.1% males). All patients received meperidine at a dose of 304 ± 133 (120 – 480) mg/day. Meperidine and normeperidine concentrations were 369 ± 60 (265 – 519) and 49 ± 17 (15 – 78) ng/mL, respectively. Intratreatment control found QTcB 370 ± 30 (305 – 433), QTcFri 353 ± 35 (281 – 429), QTcFra 360 ± 30 (299 – 429), QTcH 359 ± 27 (304 – 427), ΔQTcB +9 ± 42 (–90 to +136), ΔQTcFri +4 ± 45 (–86 to +137), ΔQTcFra +5 ± 40 (–77 to +129), and ΔQTcH +7 ± 40 (–76 to +129) ms. Meperidine concentration correlated with QTc-interval (R > 0.36) and ΔQTc (R > 0.69) but the correlation was even better for normeperidine concentration, QTc (R > 0.52) and ΔQTc (R > 0.81). Depending on the QTc correction formula used, 13 – 15 patients (22.41 – 25.86%) presented ΔQTc values > 30 ms, and 7 – 8 patients (12.07– 13.79%) showed ΔQTc values > 60 ms. Renal failure was associated with risk for ΔQTc > 30 ms of 3.74 (IC95% 1.73 – 8.10) and for ΔQTc > 60 ms of 4.27 (IC 95% 1.26 – 14.48). No patient developed arrhythmias during the study. Conclusions: Meperidine treatment causes ECG changes (QTc-interval prolongation) in high correlation with normeperidine plasma concentration. Renal failure increases the risk. Correspondence to:
Guillermo Alberto Keller, MD,
Second Chair of Pharmacology
Department of Pharmacology
School of Medicine, University of Buenos Aires
Paraguay 2155 – Piso 16, C1121ABG
Ciudad Autónoma de Buenos Aires, Argentina 
Email: [email protected]

Abstract

Clinical Nephrology, Vol. 87 – No. 3/2017 (147-151)

Acquired hemophilia A that developed during the induction of hemodialysis: the use of double-filtration plasmapheresis 

Aya Imafuku, Naoki Sawa, Yoshifumi Ubara, Kenmei Takaichi 

Department of Nephrology Center, Toranomon Hospital, Tokyo, Japan
Acquired hemophilia A (AHA) is a rare bleeding disorder caused by autoantibodies to coagulation factor VIII (FVIII). AHA onset during the induction of dialysis is extremely rare, and the management of blood access is difficult. We present a case of AHA that developed during induction of dialysis and treatment with double filtration plasmapheresis (DFPP). An 86-year-old man with chronic kidney disease was admitted to our hospital with multiple subcutaneous hemorrhages. Because of his prolonged activated partial thromboplastin time (aPTT) and high titer of inhibitors to FVIII, he was diagnosed with AHA, and prednisolone treatment was started. After 3 weeks of steroid therapy, his renal function deteriorated, and dialysis was needed. We performed femoral catheter placement under administration of recombinant activated factor VII (rFVIIa) to prevent bleeding. The patient developed catheter-related bloodstream infection and needed arteriovenous fistula (AVF) immediately. After 4 DFPP sessions, his hemostasis recovered to normal. AVF placement did not cause any complication, and he could safely undergo maintenance hemodialysis. Clinicians should suspect AHA in end-stage renal disease patients with acute onset of bleeding and an unexplained prolonged aPTT. DFPP is useful in patients with AHA that develops during induction of dialysis and requires surgical treatment. Correspondence to:
 Aya Imafuku, MD
Department of Nephrology Center
Toranomon Hospital
2-2-2 Toranomon Minato-ku, Tokyo 105-8470, Japan
Email: [email protected]

Abstract

International Journal of Clinical Pharmacology and Therapeutics, Vol. 54 – No. 11/2016 (890-898)

Effect of ulinastatin on serum inflammatory factors in Asian patients with acute pancreatitis before and after treatment: a meta-analysis 

Ling-Zhang Wang¹, Ming-Yu Luo¹, Jin-Shan Zhang², Fu-Gui Ge³, Jian-ling Chen¹, Chang-Qing Zheng⁴ 

¹Department of Emergency, ²Department of Radiology, LinYi People’s Hospital, ³Department of Surgery, Linyi Women’s and Children’s Hospital, LinYi, and ⁴Department of Gastroenterology, Shengjing Hospital, China Medical University, Shenyang, China
Objective: We applied a meta-analysis to explore the effect of ulinastatin (UTI) on the serum levels of C-reactive protein (CRP), interleukin 6 (IL-6), and tumor necrosis factor alpha (TNF-α) in Asian patients with acute pancreatitis (AP). Methods: Various databases were searched based on stringent inclusion and exclusion criteria to extract relevant cohort studies. Comprehensive Meta-analysis 2.0 (Biostat Inc., Englewood, NJ, USA) was applied for statistical analyses. Results: A total of 113 relevant studies (67 in Chinese, 46 in English) were initially retrieved. Finally, 11 eligible studies were enrolled in our meta-analysis with 399 pancreatitis patients. Meta-analysis results showed that after being treated with UTI, the serum levels of CRP, IL-6, and TNF-α were evidently decreased (CRP: SMD = –2.697, 95% CI = –4.399 ~ –0.994, p = 0.002; IL-6: SMD = –5.268, 95% CI = –9.850 ~ –0.687, p = 0.024; TNF-α: SMD = –5.666, 95% CI = –11.083 ~ –0.249, p = 0.040). Conclusion: UTI can effectively reduce the serum levels of CRP, IL-6, and TNF-α in Asian patients with AP, suggesting that UTI has anti-inflammatory effect on Asian patients with AP. Correspondence to:
Dr. Jian-ling Chen
Department of Emergency, LinYi People’s Hospital
NO.27 Jiefang Road, Lanshan District, LinYi 276000, P.R.China
Email: chenjianling1008@ 163.com

Abstract

Clinical Nephrology, Vol. 86 – No. 4/2016 (165-174)

Vitamin D levels, vitamin D supplementation, and prognosis in patients with chronic kidney disease 

Yossef Namir¹*, Matan Cohen²*, Yosef Haviv³, Itzchak Slotki¹, Linda Shavit¹ 

¹Adult Nephrology Unit, Shaare Zedek Medical Center, ²Department of Medicine, Shaare – Zedek Medical Center, Faculty of Medicine, Hebrew University, Jerusalem, and ³Soroka Medical Center and Ben Gurion University of the Negev, Beer Sheva, Israel
Background: Vitamin D (Vit D) deficiency plays a central role in the pathogenesis of chronic kidney disease (CKD) complications, both skeletal and nonskeletal. The purpose of this study was to examine whether 25(OH)D levels and supplementation with oral cholecalciferol (Vitamin D₃ (Vit D3)) are associated with morbidity and mortality among patients with significant CKD. Methods: CKD patients attending the nephrology clinic at Shaare Zedek Medical Center between July 1, 2008 and January 31, 2012, tested at least twice for 25(OH)D levels, were enrolled. Primary endpoints included death, end-stage renal disease (ESRD) requiring start of dialysis, a rise of at least 50% in serum creatinine, or composite endpoints of the above. Results: A total of 516 patients were studied, of whom 178, 257, and 81 patients had baseline vitamin D levels < 5 ng/mL, 15 – 30 ng/mL, and > 30 ng/mL, respectively. We found an association between baseline 25(OH)D level below 15 ng/mL and renal outcomes (start of dialysis or a rise of at least 50% in serum creatinine) in both crude and multivariate analyses (hazard ratio (HR) 3.17, 95% CI 1.12 – 8.94). Vit D3 supplementation demonstrated beneficial effects on combined renal outcomes and death in univariate analyses (p = 0.02). Moreover, an increment of 10 ng/mL in 25(OH)D levels was associated with a 25% reduction in mortality (HR 0.755 (95% CI 0.54 – 1.00), in crude but not adjusted analyses. Conclusions: Significant Vit D deficiency in CKD can serve as a biological marker indicating patients in whom adverse renal outcomes can be anticipated. Moreover, Vit D3 supplementation and rise of serum 25(OH)D levels may have beneficial influence on hard renal outcomes. 

*Equal contribution.Correspondence to:
Linda Shavit, MD
Adult Nephrology Unit
Shaare Zedek Medical Center
PO Box 3235, Jerusalem 91031, Israel
Email: [email protected]

Abstract

Clinical Nephrology, Vol. 86 – No. 4/2016 (175-182)

KDPI score is a strong predictor of future graft function: Moderate KDPI (35 – 85) and high KDPI (> 85) grafts yield similar graft function and survival 

Astha Gupta¹, George Francos¹, Adam Frank², Ashesh Shah² 

¹Nephrology Division, Department of Medicine and ²Transplant Division, Department of Surgery, Thomas Jefferson University, Philadelphia, PA, USA
Background: Efforts have been made to maximize the utility of each organ transplanted. Policy changes to capture unrealized graft years have been implemented utilizing the kidney donor profile index (KDPI). Understanding the impact of KDPI on long-term graft function is critical to an informed organ acceptance decision. Methods: We reviewed the records of 309 consecutive deceased adult donor kidney recipients who underwent kidney transplantation at our center. We obtained KDPI of the allografts directly from United Network for Organ Sharing (UNOS) and patients were divided into four categories: KDPI ≤ 20, KDPI 21 – 35, KDPI 36 – 85, and KDPI > 85. Results: Of the 309 recipients, 48 (15.5%) received kidneys from donors with KDPI ≤ 20, 57 (18.4%) from donors with KDPI 21 – 35, 161 (52.1%) from donors with KDPI 36 – 85, and 43 (13.9%) from donors with KDPI > 85. Older recipients were more likely to receive high KDPI kidneys (p = 0.025). Kaplan-Meier analysis demonstrated the KDPI > 35 group had worse survival than the KDPI ≤ 20 group, but KDPI 36 – 85 was not different from KDPI > 85. The rate of poor graft function differed at 1 year: 14.6% of KDPI ≤ 20 recipients, 14.3% of KDPI 21 – 35 recipients, 30.6% of KDPI 35 – 85 recipients, and 40.5% of KDPI > 85 recipients had serum creatinine greater than 2.0 mg/dL at 1 year. KDPI > 35 had statistically significantly greater incidence of poor graft function than KDPI ≤ 35 (p < 0.05). Conclusions: Our study demonstrates that high KDPI grafts behave more like moderate KDPI grafts (KDPI 35 – 85). Creatinine (Cr) greater than 2.0 mg/dL portends poorer long-term graft survival, and this outcome is similar amongst all recipients of KDPI > 35 allografts. Correspondence to:
Ashesh P. Shah, MD
Thomas Jefferson University
1025 Walnut Street, Suite 605
Philadelphia, PA 19107, USA
Email: [email protected]

Abstract

Clinical Nephrology, Vol. 86 – No. 4/2016 (183-189)

The effect of gender on aminoglycoside-associated nephrotoxicity 

Joel Neugarten, Ladan Golestaneh 

Nephrology Division, Department of Medicine, Montefiore Medical Center, Albert Einstein College of Medicine, Bronx, NY, USA
Aims: The kidney disease improving global outcomes (KDIGO) clinical practice guidelines for acute kidney injury (AKI) has endorsed the widely held belief that female gender is a risk factor for aminoglycoside-associated nephrotoxicity (AAN). In contrast, female gender is protective in animal models. In light of this dichotomy, we sought to explore this relationship in greater detail. Methods: We performed a meta-analysis of studies published between 1978 and 2015 which examined aminoglycoside nephrotoxicity and provided gender-specific data. Results: 24 studies were identified that provided univariate gender-specific data. The incidence of AAN did not differ between the sexes (odds ratio (OR) for females vs. males 1.00 (0.81, 1.22), p = 0.97, n = 5,980). Twelve studies utilized logistic regression analysis with gender as a covariate. Meta-analysis of the 5 studies that utilized multivariate analysis and reported gender-specific OR found no effect of gender on the risk of AAN (OR 0.99 (0.58, 1.69), p = 0.96, n = 2,994). Similarly, gender was not an independent risk factor for AAN in the remaining 7 studies that utilized multivariate analysis with gender as a covariate but failed to report gender-specific OR (n = 1,636). Discussion: Our meta-analysis contradicts the generally held consensus that female gender is an independent risk factor for the development of AAN. Our findings may have much wider implications insofar as AAN cannot be used as an example to support the conclusion of the KDIGO Clinical Practice Guidelines that female gender is an independent risk factor for AKI. Correspondence to:
Joel Neugarten, MD
 Renal Division, Montefiore Medical Center
111 E. 210 St., Bronx, NY 10467, USA 
Email: jneugart@ montefiore.org

Abstract

Clinical Nephrology, Vol. 86 – No. 4/2016 (190-199)

IL-1β promotes tubulointerstitial injury in  MPO-ANCA-associated glomerulonephritis 

Manabu Tashiro¹, Yoshie Sasatomi¹, Renya Watanabe¹, Maho Watanabe¹, Katsuhisa Miyake¹, Yasuhiro Abe¹, Tetsuhiko Yasuno¹, Kenji Ito¹, Naoko Ueki¹, Aki Hamauchi¹, Ritsuya Noda², Satoshi Hisano³, Hitoshi Nakashima¹ 

¹Division of Nephrology and Rheumatology, Department of Internal Medicine, Faculty of Medicine, Fukuoka University, ²Division of Nephrology, Department of Internal Medicine, Saiseikai Fukuoka General Hospital, and ³Department of Pathology, Faculty of Medicine, Fukuoka University, Fukuoka, Japan
Background: It is widely accepted that tubulointerstitial injury (TII) is caused by glomerular injury (GI) in glomerular diseases. Glomerular endocapillary inflammation may result in crescent formation and exuded protein leakage, which may induce TII in antineutrophil cytoplasmic antibody-associated glomerulonephritis (ANCAGN). However, some reports have indicated a glomerulonephritis-independent mechanism of TII in ANCAGN. The aim of this study was to determine the principle cytokines correlated with TII severity and to elucidate a characteristic mechanism for TII in ANCAGN. Methods: 28 myeloperoxidase-ANCA-positive ANCAGN patients were enrolled, and their kidney biopsy specimens were histologically evaluated with regard to GI and TII. The mRNA expression of various cytokines was examined in 28 specimens. Results: Interleukin (IL)-1β was significantly correlated with the severity of TII. The mRNA expression of Toll-like receptor 4 (TLR4) and Nod-like receptor family pyrin domain-containing-3 (NLRP3) also correlated with TII severity. Immunohistochemical analysis demonstrated that TLR4 protein was positively stained in the tubulointerstitial infiltrating cells. NRLP3 protein was detected in macrophages in the severe infiltrating area but was absent or only very faintly expressed in the glomeruli. These results indicated that NLRP3 inflammasome-dependent processing in macrophages releases the mature active form of IL-1β, which may lead to the development and deterioration of TII. Conclusions: Sterile inflammation leads to the formation of ANCA-mediated neutrophil extracellular traps (NETs), which may stimulate macrophages and dendritic cells via TLR4 and induce NF-κB-dependent mRNA expression and translation of pro-IL-1β. Simultaneously, damage-associated molecular pattern signals resulting from NETs promote NLRP3 inflammasome-dependent processing and release mature active IL-1β. Sterile inflammation utilizing the NLRP3 inflammasome might be a characteristic reaction limited to the tubulointerstitium. Thus, neutralizing IL-1β may be a promising strategy to suspend the progress of TII and improve the prognosis of chronic kidney disease resulting from ANCAGN. Correspondence to:
Hitoshi Nakashima, MD, PhD
 Division of Nephrology and Rheumatology
Department of Internal Medicine
Faculty of Medicine, Fukuoka University
Nanakuma 7-45-1, Jonan-ku 812-0180, Fukuoka, Japan 
Email: hnakashi@ fukuoka-u.ac.jp

Abstract

Clinical Nephrology, Vol. 86 – No. 4/2016 (200-202)

Prevention of recurrence of atypical hemolytic uremic syndrome post renal transplant with the use of higher-dose eculizumab 

Amy Riddell¹, Tim Goodship², Coralie Bingham¹ 

¹Royal Devon and Exeter Hospital, Barack road, Exeter, Devon and ²Institute of Genetic Medicine, Newcastle University, Central Parkway, Newcastle Upon Tyne, UK
Eculizumab, a terminal complement inhibitor, has recently been used successfully to both prevent and treat the recurrence of atypical hemolytic uremic syndrome (aHUS) post renal transplantation. We describe a case that highlights the need to monitor the effects of eculizumab on the complement system and in this case alter the dosage. Despite taking the standard recommended dose of eculizumab for an adult, this aHUS patient developed a low-grade thrombotic microangiopathy on biopsy within months of renal transplantation. Complement assays (trough CH50) showed small amounts of residual terminal pathway activity suggesting inadequate complement blockade on 1,200 mg eculizumab every 2 weeks. Following an increase in the dose of eculizumab to 1,500 mg every 2 weeks, lactate dehydrogenase (LDH), proteinuria, and creatinine decreased, and CH50 assay showed 0%. This case emphasizes the need to monitor clinical parameters and complement activity to ensure that adequate therapeutic blockade is achieved. Correspondence to:
Amy Riddell, MBBcH, MRCP
Royal Devon and Exeter, Hospital
Barack road, Exeter, Devon, EX2 5DW, UK
Email: [email protected]

Abstract

Clinical Nephrology, Vol. 86 – No. 4/2016 (203-228)

A systematic literature search and review of sodium concentrations of body fluids 

Elaine Kaptein¹, Divya Sreeramoju¹,², John Kaptein³, Matthew Kaptein¹ 

¹Department of Medicine, University of Southern California, Los Angeles, CA, ²Presence Saint Joseph Hospital-UIC, Chicago, IL, and ³Southern California Permanente Medical Group, Los Angeles, CA, USA
Background: Wide ranges of sodium concentrations for different body fluid losses have been noted with minimal substantiating data and variability among sources, leading to use of “cumulative fluid balance” regardless of composition in hospitalized patients. Aims: To define the sodium concentrations of fluid losses from the body. Method: We performed a systematic search and literature review in adult humans using PubMed database. Results: Inclusion criteria were met for 107 full-text articles. Mean sodium concentrations were significantly lower for acidic (mean ± SD: 44 ± 12 mEq/L) than for alkaline (55 ± 13 mEq/L) gastric fluid, higher for bile (185 ± 24 mEq/L) or pancreatic fluid (156 ± 3 mEq/L) than for all other body fluids, and similar for intact small bowel (119 ± 14 mEq/L) and ileostomy outputs (116 ± 25 mEq/L). Sodium concentrations were significantly greater for cholera-induced diarrhea (128 ± 18 mEq/L) and lower for osmotic-induced diarrhea (28 ± 16 mEq/L) than all other causes of diarrhea. For osmotic diarrheas, sorbitol-induced diarrhea sodium concentration was higher (63 ± 17 mEq/L) than for carbohydrate malabsorption (43 ± 20 mEq/L), lactulose (26 ± 19 mEq/L), Idolax (16 ± 13 mEq/L), or polyethylene glycol (13 ± 7 mEq/L). For secretory diarrheas, sodium concentration for idiopathic causes (53 ± 22 mEq/L) was lower than for neuroendocrine and villous tumors (75 ± 13 mEq/L) or nonosmotic laxatives (88 ± 33 mEq/L). For pleural, peritoneal, and edema fluid, sodium concentrations (137 ± 13 mEq/L) were similar to plasma. No data were found for wound fluid. Sodium concentration for sweat was 44 ± 17 mEq/L. Conclusions: This is the first in-depth review of verifiable sodium concentrations of body fluids most commonly lost in hospitalized patients. Sodium concentrations are fluid-specific and consistent. Sodium concentrations for diarrhea are associated with specific mechanisms/causes. These data should be useful to more accurately replace sodium and water content for specific body fluid losses. Correspondence to:
Elaine M. Kaptein, MD
Room 808 IRD, 2020 Zonal Avenue
Los Angeles, CA 90033, USA
Email: [email protected]

Abstract

Trace Elements and Electrolytes, Vol. 34 – No. 1/2017 (10-15)

Hair aluminum status in Croatia 

Ninoslav Mimica¹, Juraj Prejac², Vjeran Višnjević³, Andrey Skalny⁴, Berislaw Momčilović³ 

¹University Psychiatric Hospital Vrapče, Zagreb, Croatia School of Medicine, University of Zagreb, Zagreb, ²University Hospital Centre Zagreb, Department of Oncology, Zagreb, ³Institute for Research and Development of the Sustainable Ecosystems (IRES), Zagreb, Croatia, and ANO Center for Biotic Medicine, Moscow, Russia
Aluminum (Al) is an omnipresent non-essential trace element in the human environment; the risk of environmental Al exposure to the general population is on the rise world-wide. We have already shown that hair aluminum (H^Al) is a reliable long-term biological indicator of exposure to aluminum by the human body whereas whole blood is a short-term biological indicator. The aim of this paper is to assess the population Al exposure risk in the Croatian general population by analyzing H^Al in 1,073 apparently healthy persons (♂_n = 339 and ♀_n = 734) with the ICP MS; H^Al median (µg∙g^–1) was higher in men (7.64) than in women (6.18) (p < 0.01, χ²-test). We used the logistic bioassay sigmoid curve of median derivatives to analyze the natural distribution of Al in hair. The physiologically tolerable range, i.e., the linear part of the sigmoid curve, was 1.83 – 20.9 µg∙g^–1 in women and 2.39 – 27.7 µg∙g^–1 in men. Hair Al concentrations below or above this tolerable range indicate negligible low or excessively high Al exposure, respectively. Our results indicate that currently ~ 6% of Croatian men and women are overexposed to aluminum to a various degree. Correspondence to:
 Prof. Dr. Sci. Berislav Momčilović, MD
 Institute for Research and Development
of the Sustainable Ecosystems (IRES)
Srebrnjak 59, 10000 Zagreb, Croatia 
Email: [email protected]

Abstract

Clinical Nephrology, Vol. 86 – No. 5/2016 (283-286)

Icodextrin-induced acute pancreatitis in a peritoneal dialysis patient: a case report and literature review 

Sofia Rubinstein¹, Rafael Franjul¹, Sikander Surana¹, Joshua Fogel² 

¹Division of Nephrology and Hypertension, Nassau University Medical Center, East Meadow, and ²Department of Business Management, Brooklyn College, Brooklyn, NY, USA
The 7.5% icodextrin solution is widely used for long-dwell in peritoneal dialysis (PD) regimens as an alternative osmotic agent to glucose. It has been defined as a biocompatible agent because of its iso-osmolarity and is generally safe and well tolerated. Icodextrin and its hydrolyzed metabolites are found in systemic circulation. In serum, icodextrin interferes with amylase determination causing a significantly decreased plasma amylase level making it unreliable for the diagnosis of acute pancreatitis. Lipase measurement provides an alternative and accurate method for diagnosing acute pancreatitis (AP) in patients using icodextrin. Icodextrin-induced acute pancreatitis is not well described. The literature appears limited to two case reports. We describe a case of a man with end-stage renal disease (ESRD) on PD who developed acute pancreatitis following icodextrin use. We also provide a novel possible mechanism for understanding how icodextrin causes AP. Correspondence to:
Sofia Rubinstein, MD
Division of Nephrology and Hypertension
Nassau University Medical Center
2201 Hempstead Turnpike, Box 49
East Meadow, NY, 11554, USA
Email: [email protected]

Abstract

Trace Elements and Electrolytes, Vol. 34 – No. 1/2017 (34-39)

The levels of trace elements and homocysteine in arterial hypertension 

Gürkan Çıkım¹, Kenan İzgi², Ekrem Aksu³ 

¹Necip Fazil City Hospital, Laboratory of Biochemistry, Kahramanmaras, ²Erciyes University, Faculty of Medicine, Department of Medical Biochemistry, Kayseri, and ³Necip Fazil City Hospital, Department of Cardiology, Kahramanmaras, Turkey
Objective: In this study, we evaluated the levels of zinc, copper, iron, and homocysteine in 50- to 55-year-old male patients with newly diagnosed hypertension, and in patients with a diagnosis of hypertension for at least 3 years to a maximum of 5 years who were not under medication. Materials and methods: We evaluated the levels of zinc, copper, iron, and homocysteine in the groups of hypertension patients and in healthy individuals. The study included 50- to 55-year-old male patients who were admitted to the outpatient cardiology clinic of Kahramanmaras Necip Fazil City Hospital, presenting with chest pain, headache, and dizziness. The determination of zinc and copper levels in serum samples was performed using Perkin Elmer Analyst 800 Flame atomic absorption spectroscopy. Iron was measured using a colorimetric assay (Roche Hitachi Cobas C501 autoanalyzer). Homocysteine level was analyzed using ELISA. Results: The serum levels of zinc and copper in patients with newly diagnosed hypertension (group II) and in patients with a diagnosis of hypertension for 3 – 5 years (group III) were significantly lower compared to the control group (group I) (p < 0.001). Accordingly, the levels of homocysteine and iron in group II and group III were significantly higher compared to the control group (p for all < 0.001). There was no significant difference in the serum levels of iron and copper between the groups with hypertension (group II vs. group III) (p = 0.366; p = 0.295, respectively). Whereas homocysteine levels in group III were significantly higher than in group II (p < 0.001); zinc levels in group III were significantly lower than in group II (p < 0.001). Conclusion: Considering these results, we believe that the levels of iron, copper, homocysteine, and zinc have an effect on hypertension development. In addition, the effects of homocysteine and zinc on hypertension might be continued during disease progression. Thus, we believe that the levels of homocysteine and zinc could be an important parameter in the follow-up of hypertension. Additionally, it is necessary to add elements such as copper and zinc as well as antioxidants in the diet of these patients, and to prevent the increase of iron levels in hypertension. Correspondence to:
Gurkan Cikim, MD
Necip Fazil City, Hospital,
Laboratory of Biochemistry
46050, Kahramanmaras, Turkey
Email: [email protected]

Abstract

Clinical Nephrology, Vol. 86 – No. 5/2016 (253-261)

Second vascular access after failure of the first fistula in the elderly 

Tammy Hod¹, Alexander Goldfarb-Rumyantzev², Bhanu Patibandla³, Akshita Narra⁴, Robert Brown² 

¹Division of Nephrology, Brigham and Women’s Hospital and Harvard Medical School, ²Division of Nephrology, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, MA, ³Division of Pulmonary and Critical Care Medicine, Oregon Health and Science University, OR, and ⁴Department of Medicine, University of Connecticut School of Medicine, Farmington, CT, USA
Background: In patients with failure of an initial arteriovenous fistula (AVF), a subsequent vascular access is needed before hemodialysis (HD) initiation. Methods: To assess the optimal access strategy after a failed AVF, we linked data from the US Renal Data System with Medicare claims data identifying 21,436 patients ≥ 67 years old who started HD between January 1, 2005, and December 31, 2008, with an AVF placed as their first predialysis access. Of the 10,568 subjects whose AVF failed, 1,796 patients had an AVF placed as a second access predialysis (AVF2 group) and 399 patients had an arteriovenous graft placed as a second access predialysis (AVG2 group). Second access success was defined as HD initiation for the first HD session using this access avoiding need for a catheter. Results: The mean age for AVF2 and AVG2 groups was 75.9 ± 6.0 and 75.9 ± 5.9 years with a significantly greater percentage of men and whites in the AVF2 group and women and blacks in the AVG2 group. Overall, 53% of AVF2 group initiated dialysis using AVF2, and 66% of AVG2 group started dialysis using AVG2 (p < 0.001). The following variables were found to be associated with AVF2 failure: female gender, peripheral vascular disease (PVD), interventional procedures, and the absence of pre-ESRD nephrology care. AVG2 failure was associated with white race, lower body mass index (BMI), and the absence of pre-ESRD (end-stage renal disease) nephrology care. Conclusion: Since the success rate to avoid the use of a catheter was significantly higher in the AVG2 group than in the AVF2 group, an AVG may be a preferable choice of second access in certain patients, especially in females, blacks and those with PVD. Correspondence to:
Robert S. Brown, MD 
Division of Nephrology
Beth Israel Deaconess Medical Center
185 Pilgrim Rd, FA 811, Boston, MA 02215, USA 
Email: [email protected]

Abstract

Clinical Nephrology, Vol. 86 – No. 5/2016 (242-252)

Modulation of circulating endothelial progenitor cells by erythropoiesis-stimulating agents in patients with chronic kidney disease stage G5 and 5D 

Takashi Naito¹#⁵, Tsutomu Sanaka², Hayato Mikami¹#³, Asuka Soga³, Kotoko Yamatani¹#³, Kaori Segawa³, Moe Kawashima³, Tetsuya Yoshikura¹, Jun Niwayama⁴, Hideki Nishimura⁵, Tetsuya Ogawa⁵, Akitoshi Ando¹, Akira Teramoto⁶, Kosaku Nitta³ 

¹Department of Medicine, Tokyo Rosai Hospital, ²Life Style Disease Center, Edogawa Hospital, ³Department of Medicine, Kidney Center, Tokyo Women’s Medical University, Tokyo, ⁴Department of Medicine, Sumiyoshi Clinic Hospital, Ibaraki, ⁵Department of Medicine, Medical Center East, Tokyo Women’s Medical University, and ⁶Department of Neurosurgery, Tokyo Rosai Hospital, Tokyo, Japan
Aims: Circulating endothelial progenitor cells (EPCs) play a pivotal role in vasculogenesis and promote angiogenesis by secreting growth factors. Recent studies have suggested that erythropoietin (EPO) may accelerate not only angiogenesis but also vasculogenesis, beyond erythropoiesis. The aim of this study was to investigate whether two erythropoiesis-stimulating agents (ESAs) modulate vascular-related factors and EPC mobilization in patients with chronic kidney disease stage G5 and dialysis (CKD G5 and 5D). Materials and methods: We conducted a 12-week prospective study in 63 patients; 21 patients received recombinant human erythropoietin (rhEPO) (EPO group, 4,565.5 ± 1,994.4 IU/week), 21 patients received darbepoetin (DA) (DA group, 40.1 ± 13.8 µg/week), and 21 patients received no ESAs (no-ESA group). Vascular mediators, including EPCs, vascular endothelial growth factor, matrix metalloproteinase-2 (MMP-2), high-sensitivity C-reactive protein, and asymmetric dimethyl arginine, were measured at 0 and 12 weeks. EPCs were measured by flow cytometry as CD45^lowCD34⁺CD133⁺ cells. We also performed a subanalysis of dialysis (5D) patients (n = 32) in the three groups. Results: In the EPO group, EPC count increased significantly from 0 to 12 weeks in a dose-dependent manner (r = 0.62, p = 0.005), and the increase was more conspicuous in the subgroup of dialysis 5D patients. In the DA group, the EPC number did not change at 12 weeks. Neither rhEPO nor DA affected the serum levels of the aforementioned biomarkers other than EPC. Conclusion: We speculate that the pleiotropic effects of rhEPO and DA beyond their hematopoietic effects may differ between CKD G5 and 5D patients. Correspondence to:
Dr. Takashi Naito 
Division of Nephrology, Department of Medicine
Tokyo Rosai Hospital
4-13-21 Omori-minami, Tokyo 143-0013, Japan  
Email: takashi020304@ yahoo.co.jp and

Abstract

Clinical Nephrology, Vol. 86 – No. 5/2016 (262-269)

Data completeness as an unmeasured confounder in dialysis facility performance comparison with 1-year follow-up 

Jiannong Liu¹, Mahesh Krishnan², Jincheng Zhou¹#³, Kimberly Nieman¹, Yi Peng¹, David Gilbertson¹ 

¹Chronic Disease Research Group, Minneapolis Medical Research Foundation, Minneapolis, MN, ²DaVita Healthcare Partners, Denver, CO, and ³Division of Biostatistics, University of Minnesota, Minneapolis, MN, USA
Aims: Standardized mortality and hospitalization ratios (SMRs, SHRs) are used to measure dialysis facility performance in the US, with adjustment for demographics and comorbid conditions derived from the end-stage renal disease (ESRD) Medical Evidence (ME) Report. Sensitivities are low for ME-based comorbidity, and levels of under-reporting may differ among facilities. We aimed to assess the effect of data inaccuracy on performance comparison. Methods: Using the United States Renal Data System ESRD database, we included patients who initiated hemodialysis July 1 – December 31 in each of the years 2006 – 2010, had Medicare as primary payer, were aged ≥ 66 years, and had no prior transplant. Patients were followed from dialysis initiation to the earliest of death, transplant, modality change, or 1 year. SMRs and SHRs were calculated for for-profit/non-profit and rural/urban facilities for ME-based and claims-based comorbidity, separately. Cox models were used for expected number of deaths and piecewise Poison models for expected number of hospitalizations. Comorbidity agreement was measured by κ-statistic. Testing of differences between ME-based and claims-based SMRs/SHRs was performed by bootstrap. Results: In all, 73,950 incident hemodialysis patients were included. κ-values for comorbidity agreement were low, < 0.5, except for diabetes (0.77). Percentages of claims-based comorbidity were similar for for-profit and non-profit facilities; ME-based comorbidity was lower for for-profit facilities. Differences between ME-based and claims-based SMRs/SHRs were statistically significant. Compared with ME-based SMRs/SHRs, claims-based ratios decreased 0.9/0.6% for for-profit and 1/0.7% for urban facilities and increased 3.4/2.8% for non-profit and 5.9/4.1% for rural facilities. Conclusions: Comorbidity data source may affect performance evaluation. The impact is larger for smaller groups. Correspondence to:
Jiannong Liu, PhD 
Chronic Disease Research Group
Minneapolis Medical Research Foundation
914 South 8th Street, Suite S2.100,
Minneapolis, MN 55404, USA 
Email: [email protected]

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