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Abstract

Clinical Nephrology, Vol. 76 – No. 1/2011 (1-8)

De novo once-monthly darbepoetin alpha treatment for the anemia of chronic kidney disease using a computerized algorithmic approach

E. Chalhoub, S. Frinak, G. Zasuwa, M.D. Faber, E. Peterson, A. Besarab and J. Yee

Henry Ford Hospital, Division of Nephrology and Hypertension, Detroit, MI, USA
Background: Anemia of chronic kidney disease (CKD) has been traditionally treated by erythropoiesis-stimulating agents (ESAs) and/or iron following manual determination of dose. We hypothesized that once-monthly (QM) algorithmically dosed darbepoetin α (DA) and iron administration would successfully treat anemia of CKD in ESA-naïve CKD subjects. Methods: QM DA and iron doses were determined via a computerized program targeting a hemoglobin (Hb) of 10.5 – 12.5 g/dl in anemic, ESA-naïve, CKD Stages 3 – 5 subjects. Six consecutive QM doses were administered. Hb, ferritin, and transferrin saturation were recorded. Data are presented as means ± standard deviation. Results: Anemia was identified in 133 subjects, with a mean follow-up of 188 days. DA doses and Hb were significantly greater at Months 3 and 6 compared to baseline (p < 0.05); DA doses were 109 ± 68 μg and 118 ± 91, respectively, at Months 3 and 6. Hemoglobin levels were correspondingly 11.3 ± 1.1 g/dl and 11.3 ± 1.0. 78% of patients achieved the target Hb by 6 months of therapy. The elevation of Hb was greater in non-proteinuric than proteinuric subjects at 6 months of treatment (11.6 ± 0.8 g/dl vs. 11.0 ± 1.1; p < 0.05), despite lower DA dose (96 ± 76 μg vs. 139 ± 98; p < 0.05). Conclusion: Successful treatment of the anemia of CKD by QM DA based upon a computerized dosing program was achieved by 6 months in 78% of ESA-naïve, CKD subjects.Correspondence to:
E. Chalhoub, MD
Division of Nephrology and Hypertension
2799 West Grand Blvd., CFP-517
Detroit, MI 48202, USA
Email: echalho1@hfhs.org

Abstract

Clinical Nephrology, Vol. 76 – No. 1/2011 (9-15)

Fewer dose changes with once-monthly C.E.R.A. in patients with chronic kidney disease

J.F.E. Mann¹, A. de Francisco², G. Nassar³ and B. Canaud⁴

¹KfH Kidney Center, Munich, and Department of Medicine IV, University of Erlangen-Nurnberg, Germany, ²Hospital Universitario Marqués de Valdecilla, Santander, Spain, ³Renal Research Inc., The Kidney Institute, Houston, TX, USA, and ⁴Nephrology, Dialysis and Intensive Care Unit, Lapeyronie University Hospital, CHRU Montpellier, Montpellier, France
Background: Frequent dosing and requirements for dose adjustments of erythropoiesis-stimulating agents (ESAs) create significant burdens for healthcare providers and have been associated with hemoglobin (Hb) cycling, hampering maintenance of target Hb levels. We compared the frequency of dose changes in dialysis patients who received methoxy polyethylene glycolepoetin beta; (a continuous erythropoietin receptor activator (C.E.R.A.)) or a shorter-acting ESA. Methods: Data were analyzed from three Phase III maintenance trials, using almost identical protocols, in dialysis patients treated with C.E.R.A. every 2 weeks (q2w) or every 4 weeks (q4w) or a comparator ESA (epoetin or darbepoetin alpha; at their previous dose/administration interval). Dosage was adjusted to maintain Hb ± 1 g/dl of baseline and 10 – 13.5 g/dl during titration (28 weeks) and evaluation (8 weeks), and 11 – 13 g/dl during follow-up (16 weeks). Results: Data were analyzed from 564 patients treated with C.E.R.A. q2w, 410 with C.E.R.A. q4w and 572 with comparator ESA at their usual dosing interval. Significantly fewer dose changes were needed in patients receiving C.E.R.A. q2w (p < 0.05) or C.E.R.A. q4w (p < 0.001) than in patients treated with comparator ESAs. Conclusion: This retrospective analysis suggests that C.E.R.A. q4w maintains Hb levels in dialysis patients and requires fewer dose changes compared with other ESAs.Correspondence to:
Prof. Dr. med. J.F.E. Mann
KfH Nierenzentrum
Isoldenstr. 15
80804 Munich, Germany
Email: Johannes.mann@kms.mhn.de

Abstract

Clinical Nephrology, Vol. 76 – No. 1/2011 (16-22)

Measurements on the routine chest radiograph as prognostic markers in Chinese peritoneal dialysis patients

N. Gao, B.C.-H. Kwan, K.-M. Chow, K.-Y. Chung, C.-B. Leung, P.K.-T. Li and C.-C. Szeto

Department of Medicine, Prince of Wales Hospital, The Chinese University of Hong Kong, Shatin, Hong Kong, China
Background: Fluid overload is a common problem in peritoneal dialysis (PD) patients. Cardiothoracic ratio (CTR) and vascular pedicle width (VPW) in routine chest radiograph are useful indicators of intravascular volume status and may represent important prognostic factors of PD patients. Methods: We measured VPW and CTR in 286 unselected prevalent PD patients. VPW was further adjusted for the thoracic diameter (VPWR). One-year actuarial survival, technique survival, and duration of hospitalization were analyzed. Results: The mean values of VPW, CTR, VPWR were 47.31 ± 4.73 mm, 0.542 ± 0.074, 0.170 ± 0.024, respectively. VPW correlated with age (r = 0.143; p = 0.016), body weight (r = 0.371; p < 0.001), body height (r = 0.271; p < 0.001), and Charlson’s index score (r = 0.153; p = 0.01). One-year patient survival was 87.8%, and technique survival was 82.2%. None of the radiological measurements had an independent effect on one-year actuarial or technique survival by multivariate analysis. Both CTR and VPWR correlated with the duration of hospitalization (r = 0.192 and 0.186, respectively (p = 0.001 and 0.002). Multivariate regression analysis by log-linear modeling showed that independent predictors of one-year hospitalization were VPWR, serum albumin, and SGA overall score. Conclusions: In Chinese PD patients, VPW was significantly correlated with age, body weight, body height and Charlson’s index score. VPWR was an independent predictor of the duration of hospitalization. Further studies are needed to confirm the prognostic value of these radiographic measurements in PD patients.Correspondence to:
Dr. C.C. Szeto, MD, FRCP, Professor
Department of Medicine & Therapeutics
Prince of Wales Hospital
Chinese University of Hong Kong
Shatin, N.T., Hong Kong, China
Email: ccszeto@cuhk.edu.hk

Abstract

Clinical Nephrology, Vol. 76 – No. 1/2011 (23-28)

Saliva urea dipstick test: application in chronic kidney disease

J.G. Raimann¹,²,³, W. Kirisits³, E. Gebetsroither³, M. Carter¹, J. Callegari¹, L. Rosales¹, N.W. Levin¹ and P. Kotanko¹,²,³

¹Renal Research Institute, ²Beth Israel Medical Center, New York City, NY, USA, and ³Department of Internal Medicine, Krankenhaus der Barmherzigen Brüder, Graz, Austria
Background: A noninvasive test for determining elevated levels of blood urea nitrogen (BUN) may be useful under circumstances in which there is limited access to laboratories. Because saliva urea nitrogen (SUN) parallels BUN, we investigated the diagnostic performance of a semiquantitative SUN dipstick to test for elevated BUN levels in patients with chronic kidney disease (CKD). Materials and methods: Patients with CKD Stages 1 to 5D were studied. 50 µl of saliva were transferred onto the SUN test strip (Integrated Biomedical Technology, Elkhart, Indiana, IN, USA). SUN was determined after 1 minute by visual comparison of the color of the moistened test pad with 6 calibrated color blocks. Interobserver reproducibility was evaluated by independent observers, masked to urea concentrations of 6 calibrated urea solutions. Correlation between SUN and BUN was quantified by Spearman’s rank correlation coefficient (R_S), Kappa Statistic was employed to evaluate within-sample reproducibility of duplicates. Receiver operating characteristic (ROC) analysis was used to assess the diagnostic performance of SUN. Results: 68 patients (31 females, 60 ± 14 years; 34 hemodialysis patients, 34 patients CKD Stages 1 – 4) were studied. Interobserver coefficient of variation was 4.9% at SUN levels > 50 mg/dl; within-sample reproducibility was 90%. SUN and BUN were correlated significantly (R_S = 0.63; p < 0.01). Elevated BUN was diagnosed with high accuracy by SUN determination (area under the ROC curve: 0.90 (95% CI 0.85 – 0.95)). Conclusion: Semiquantitative dipstick measurements of SUN can reliably identify CKD patients with elevated BUN levels.Correspondence to:
J.G. Raimann, MD
Renal Research Institute
207 East 94th Street, Suite 303
New York, NY 10128, USA
Email: j.raimann@gmx.net

Abstract

Clinical Nephrology, Vol. 76 – No. 1/2011 (29-39)

Viral hepatitis in renal transplantation

H. Papafragkakis¹, F. Fabrizi² and P. Martin³

¹Center for Liver Diseases, Miller School of Medicine, University of Miami, Miami FL, USA, ²Division of Nephrology and Dialysis, Maggiore Hospital, IRCCS Foundation, Milano, Italy, and ³Center for Liver Diseases, Miller School of Medicine, University of Miami, Miami, FL, USA
Chronic viral hepatitis remains common in the hemodialysis (HD) and renal transplantation population although measures to limit spread of hepatitis infection in HD units have markedly reduced its prevalence. Our review focuses on the current management of hepatitis B and C infections in renal transplant candidates before and after renal transplantation.Correspondence to:
P. Martin, MD
Center for Liver Diseases
Miller School of Medicine
University of Miami
1500 N.W. 12th Avenue, Suite 1101-E
Miami, FL 33136, USA
Email: PMartin2@med.miami.edu

Abstract

Clinical Nephrology, Vol. 76 – No. 1/2011 (40-48)

Epstein-Barr virus load for early detection of lymphoproliferative disorder in pediatric renal transplant recipients

M. Ishihara¹, E. Tanaka², T. Sato¹, H. Chikamoto², M. Hisano², Y. Akioka², S. Dohno¹, A. Maeda¹, M. Hattori², H. Wakiguchi¹ and M. Fujieda¹

¹Department of Pediatrics, Kochi Medical School, Kochi University, Kochi, and ²Department of Pediatric Nephrology, Kidney Center, Tokyo Women’s Medical University, School of Medicine, Tokyo, Japan
Aim: The aims of this study were to establish a protocol for monitoring Epstein-Barr virus (EBV) infection for identification of pediatric renal transplant recipients with a high risk of developing posttransplant lymphoproliferative disorder (PTLD) and to predict the development of PTLD. Subjects and methods: Peripheral blood mononuclear cells (PBMCs) and plasma EBV loads were measured by nested PCR (n-PCR) and real-time PCR (r-PCR) every 1 – 3 months after grafting in 17 pediatric recipients who were seronegative for EBV before grafting (4 with EBV-associated symptoms, including 2 with PTLD (Group A); 6 with asymptomatic persistent high EBV loads in PBMCs of > 1,000 copies/µgDNA for over 6 months (Group B); and 7 with neither EBV-associated symptoms nor persistent high EBV loads in PBMCs (Group C)). Results: n-PCR revealed EBV-DNA in PBMCs from all patients. The EBV genome was present in plasma in 3 (75%), 1 (17%), and 0 (0%) in Groups A, B and C (p < 0.01 for A vs. B and A vs. C). EBV loads detected by r-PCR in PBMCs were significantly higher in Groups A (p < 0.05) and B (p < 0.01) compared to Group C. EBV genomes in plasma were detected by n- and r-PCR in only the 2 cases with PTLD. One patient with lymphadenitis in Group A and 1 patient in Group B had EBV-DNA in plasma based on n-PCR, but the viral loads using r-PCR were < 250 copies/ml. Conclusion: EBV loads in PBMCs alone are insufficient for predicting EBV-associated symptoms including PTLD. Plasma EBV loads (over 250 copies/ml) estimated by r-PCR may be useful to distinguish PTLD from other EBV-associated diseases or asymptomatic viremia.Correspondence to:
M. Fujieda, MD
Department of Pediatrics
Kochi Medical School
Kochi University
Kohasu, Oko-cho, Nankoku
Kochi 783-8505, Japan
Email: fujiedam@kochi-u.ac.jp

Abstract

Clinical Nephrology, Vol. 76 – No. 1/2011 (49-56)

Henoch-Schönlein purpura in adults is not uncommon in elderly patients with an adverse prognosis

M. Schaier¹, J. Freitag¹, R. Dikow¹, C. Sommerer¹, M.-L. Gross-Weißmann², R. Waldherr², K. Andrassy¹, M. Zeier¹ and V. Schwenger¹

Department of ¹Nephrology and ²Pathology, University of Heidelberg, Heidelberg, Germany
Background: Henoch-Schönlein purpura (HSP) is a fairly common disease in children and adolescents. There are only limited data available for adults. Methods: A retrospective analysis was conducted to study renal manifestations in patients with HSP treated in our institution between 1982 and 2007. We divided our adult cohort according to age – under or over 60 years – to examine differences in elderly patients. Results: HSP was identified in 2.2% of patients referred to us for kidney biopsy. Purpuric lesions and renal involvement were found in all patients. An important triggering factor for the development of HSP in our series was chronic alcohol intake. Forty percent of our patients fulfilled the WHO criteria for alcoholics. Renal involvement was particularly prominent in patients over 60 years of age. At disease onset, estimated glomerular filtration rate (eGFR) was 63% lower in the elderly. Within a median follow-up of 8 years, renal function was significantly better in younger adults than in the elderly. 32% of the elderly have shown Modification of Diet in Renal Disease (MDRD) < 20 ml/min/1.73 m² in contrast to only 7% in patients < 60 years. Furthermore, significantly more elderly patients reached end-stage renal failure. Conclusion: The data indicate that renal manifestation of HSP in the elderly is severe and its outcome relatively poor, and worsens when compared to patients < 60 years.Correspondence to:
Dr. M. Schaier
University Hospital Heidelberg
Department of Nephrology
Im Neuenheimer Feld 162
69120 Heidelberg, Germany
Email: matthias_schaier@med.uni-heidelberg.de

Abstract

Clinical Nephrology, Vol. 76 – No. 1/2011 (57-63)

Prednisone monotherapy induced remission in a group of patients with membranous lupus nephritis

C. Bitencourt Dias¹, C.C. Pinheiro¹, P. Malafronte¹, S. Titan¹, G. Alves de Brito², J. Gera Abrão², V. dos Santos Silva², R. Toledo Barros¹ and V. Woronik¹

¹Division of Nephrology, Department of Internal Medicine, University of São Paulo and ²Departament of Internal Medicine, Hospital das Clínicas da Faculdade de Botucatu, University Estadual Paulistana, São Paulo, Brazil
The treatment of membranous lupus nephritis (MLN) is still controversial in the literature. We conducted a retrospective analysis of patients in two medical centers of São Paulo-Brazil in order to evaluate the clinical response in patients submitted to either a regimen with prednisone alone or to a double immunosuppressive regimen (prednisone plus cyclophosphamide or prednisone plus azathioprine). Methods: MLN female patients were enrolled in this retrospective study conducted from February 1999 to June 2007. Data were collected from the patients’ medical charts. Race distribution was similar in both groups: Caucasian (72.3%) and Afro-Latin-American (27.7%). The prednisone regimen consisted of 1 mg/kg/day for 8 weeks and tapering until 0.1 mg/kg/day (n = 29). The double immunosuppressive treatment consisted of the same doses of prednisone plus monthly intravenous cyclophosphamide or azathioprine for 6 months (n = 24). Criteria for remission (complete and partial) and renal function loss as well as flare criteria followed those used in the literature. Results: There was no difference between the prednisone group and the double immunosuppressive group regarding age (33.2 ± 9.4 vs. 29.1 ± 9.1 y), estimated GFR (76.5 ± 26.6 vs. 74.1 ± 39.6 ml/min/1.73 m²), serum albumin (2.8 ± 0.7 vs. 2.6 ± 0.3 g/dl), positive ANA (87.5 vs. 90.0%), positive anti- dsDNA (47.6 vs. 44.0%), renal SLEDAI indices (6.6 ± 2.6 vs. 7.0 ± 3.1), follow-up time (71 ± 46 vs. 62 ± 45 months), as well as proteinuria (3.1 ± 1.9 vs. 4.8 ± 2.4 g/day) and number of non-nephrotic patients (6 in the prednisone group vs. 3 in the double immunosuppressive group). The prednisone group presented higher C3 values (85.2 ± 31.5 vs. 62.3 ± 41.6 U/ml, p = 0.04). Clinical and laboratory characteristics at 6 months and at last follow-up did not reveal any differences between treatment regimens. Renal survival after an 8-year follow-up did not differ in both groups (prednisone group 86.2% vs. double immunosuppressive group 75%), and patients in both groups showed a high rate of renal flares (prednisone group 51.7% vs. double immunosuppressive group 62.5%). Univariate analysis showed that only patient age predicted flares (r = –0.048, p = 0.04). Borderline significance was obtained for proteinuria analysis (p = 0.07). Adverse effects did not differ between the groups. Conclusions: A regimen of corticosteroids in MLN induced a high remission rate after 6 months. Both treatment regimens showed a high flare rate and age was the only predictive parameter (r = –0.048, p = 0.04). Renal survival after 8 years did not differ between the groups.Correspondence to:
C.B Dias, PhD, MD
Rua Francisco Cruz 287
Apto 104
04117091, São Paulo SP, Brazil
Email: cristianebitencourt@uol.com.br

Abstract

Clinical Nephrology, Vol. 76 – No. 1/2011 (64-67)

Focal segmental glomerulosclerosis and partial deletion of chromosome 6p: a case report

A. Izu, H. Yanagida, K. Sugimoto, S. Fujita, M. Okada and T. Takemura

Department of Pediatrics, Kinki University School of Medicine, Osaka, Japan
´We treated a patient with 6p partial deletion syndrome diagnosed after proteinuria was detected during developmental examination 3 years after birth. External anomalies included ocular hypertelorism, saddle nose, elongated philtrum, tent-like lips, and low-set auricles. Mental retardation was evident. The karyotype was 46,XX,del(6) (p.22.1-p22.3) with an interstitial deletion. The kidneys showed no abnormality on imaging such as hydronephrosis, atrophy, or malformation. Examination of a renal biopsy specimen disclosed focal segmental glomerulosclerosis. No cardiac anomaly or Rieger anomaly, which often are present in this syndrome, were noted.Correspondence to:
T. Takemura, MD, PhD
Department of Pediatrics
Kinki University School of Medicine
377-2 Ohno-higashi
Osaka-Sayama 589-8511, Japan
Email: tsukasa@med.kindai.ac.jp

Abstract

Clinical Nephrology, Vol. 76 – No. 1/2011 (68-73)

Hemolytic uremic syndrome and rhabdomyolysis in a patient with succinate coenzyme Q reductase (complex II) deficiency

M.V. Micheletti¹, G. Lavoratti¹, S. Gasperini², M.A. Donati² and I. Pela¹

¹Pediatric Nephrology, Department of Pediatrics, and ²Center for Neuromuscular Diseases, Department of Nervous System, University of Florence, Meyer Hospital, Florence, Italy
Hemolytic uremic syndrome (HUS) is characterized by microangiopathic hemolytic anemia, thrombocytopenia and acute renal failure. Besides diarrhea-associated HUS, due to verotoxin-producing Escherichia coli, in children HUS without prodromal diarrhea may be associated with other infectious and autoimmune diseases, genetic defects of the complement-regulator alternative-pathway, and inborn errors of vitamin B12 metabolism. Rhabdomyolysis is the dissolution of skeletal muscle due to various causes, including inborn errors of metabolism. Recurrent rhabdomyolysis and HUS have been previously described in one patient with a genetic defect of oxidative phosphorylation. We report the case of a 2-year-old boy with recurrent HUS and rhabdomyolysis in whom a succinate coenzyme Q reductase (complex II) deficiency was diagnosed. We hypothesize that defects of oxidative phosphorylation could be another etiological factor in atypical HUS.Correspondence to:
Prof. I. Pela
Pediatric Nephrology Unit
Department of Pediatrics
Viale G. Pieraccini 24
50139 Florence, Italy
Email: ivana.pela@unifi.it

Abstract

Clinical Nephrology, Vol. 76 – No. 1/2011 (74-77)

Goodpasture’s disease complicating human immunodeficiency virus infection

P. Singh¹, M. Barry² and A. Tzamaloukas³

¹Division of Nephrology, ²Department of Pathology, UNM Health Sciences Center, University of New Mexico, and ³Renal Section (¹¹¹C), Raymond G Murphy VA Medical Center, Albuquerque, NM, USA
Goodpasture’s disease in association with human immunodeficiency virus (HIV) is rarely observed. Herein, we report a case of a 33-year-old Hispanic male who had both HIV and hepatitis C, and was subsequently diagnosed with autoantibodies to the glomerular basement membrane. On initial presentation he was anuric and hyperkalemic with an elevated creatinine. Hemodialysis was initiated, and a renal biopsy showed findings diagnostic of anti-glomerular basement membrane crescentic glomerulonephritis. Immunofluorescence microscopy showed strong (3+) linear staining of glomerular basement membranes by IgG, kappa; and lambda; light chains, and focal weaker staining of glomerular basement membranes for C3. Plasmapheresis, steroids and cyclophosphamide were all considered in treating this complex case. The patient received therapy with plasmapheresis and steroids during his initial hospitalization, but his renal function did not improve. He was discharged on hemodialysis 3 times per week. On a subsequent admission, the patient presented with symptoms and signs suggestive of pulmonary hemorrhage. Thus, plasmapheresis and cyclophosphamide were begun. His pulmonary symptoms improved with therapy, but he continued to require long-term hemodialysis. The development of Goodpasture’s syndrome in a patient with HIV infection creates diagnostic and therapeutic dilemmas. The decision to treat the patient with immunosuppressive medications should lead to enhanced surveillance for infections.Correspondence to:
P. Singh, MD
Division of Nephrology
University of New Mexico
MSC 10-5550
Albuquerque, NM 87131, USA
Email: psingh@salud.unm.edu

Abstract

Clinical Nephrology, Vol. 76 – No. 1/2011 (78-82)

Two cases of nephrotic syndrome (NS)-induced acute kidney injury (AKI) associated with renal hypouricemia

Y. Takeda¹, A. Abe¹, S. Nakanishi¹, M. Umezu¹, K. Hirano², H. Hayakawa², I. Ohno², K. Ichida², Y. Yamaguchi³, T. Hosoya² and M. Fukagawa¹

¹Division of Nephrology and Kidney Center, Kobe University School of Medicine, Hyogo, ²Division of Kidney and Hypertension, Department of Internal Medicine, Jikei University School of Medicine, Tokyo, and ³Yamaguchi’s Pathology Laboratory, Matsudo, Japan
Renal hypouricemia is a clinical disorder attributed to an increased renal urate excretion rate and is well known to involve a high risk of urolithiasis and exercise-induced acute kidney injury (AKI). This report concerns two interesting cases of nephrotic syndrome (NS)-induced AKI associated with renal hypouricemia. A 64-year-old female (Case 1) and a 37-year-old male (Case 2) were hospitalized because of AKI (serum creatinine: 2.07 mg/dl and 3.3 mg/dl, respectively), oliguria and NS. They were treated with prednisolone and temporary hemodialysis. Renal function improved, but hypouricemia persisted during hospitalization. Histological findings in both cases led to a diagnosis of minimal change nephrotic syndrome and identification of the diuretic phase of tubulointerstitial damage because of findings such as acute tubular necrosis. Furthermore, distal tubules of Case 2 showed an amorphous mass, possibly a uric acid crystal. Analysis of the two cases with the URAT1 gene, encoded by SLC22A12, found a homozygous mutation in exon 4 (W258stop) of each one. Our cases show that patients with renal hypouricemia may be susceptible to AKI without involvement of exercise if they possess some facilitators. Renal hypouricemic patients should therefore be carefully examined for all complications from renal hypouricemia because of high risk of AKI.Correspondence to:
M. Fukagawa, MD, PhD, FJSIM, FASN
Professor of Medicine
Division of Nephrology, Endocrinology and Metabolism
Tokai University School of Medicine
143 Shimo-Kasuya
Isehara, 259-1193, Japan
Email: fukagawa@tokai-u.ac.jp

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Volume 76, No. 1/2011(July)