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Abstract

D. Dragovic, J.L. Rosenstock, S.J. Wahl, G. Panagopoulos, M.V. DeVita and M.F. Michelis

¹Division of Nephrology, and ²Department of Pathology, Lenox Hill Hospital, New York, NY, USA
Background: Idiopathic focal segmental glomerulosclerosis (FSGS) is one of the leading causes of the nephrotic syndrome in adults and an important cause of end-stage renal disease. Its incidence has dramatically increased in the last two decades and it is especially prevalent among black patients. The trend of FSGS incidence has not been reported beyond 1997. Methods: We retrospectively reviewed all renal biopsies performed at our institution between 1986 and 2002 and identified patients with diagnoses consistent with primary glomerulopathy (PG), which included: minimal-change disease (MCD), idiopathic focal segmental glomerulosclerosis (FSGS), membranous nephropathy (MGN), IgA nephropathy (IgA), membranoproliferative glomerulonephritis (MPGN) and mesangioproliferative glomerulonephritis. Patients with possible secondary causes for their renal disease were excluded. Clinical data at the time of biopsy and follow-up data were collected and analyzed. Results: During the period from January 1986 – December 2002, 299 renal biopsies were performed and 132 patients were diagnosed with PG. FSGS was the most common form of PG representing 37.8% of all PG followed by IgA 27.3%, MGN 16.6% and MCD 9.1%. Among FSGS patients 59% were females, 64% had nephrotic range proteinuria and 54% had the nephrotic syndrome. Mean serum creatinine was 2.0 ± 0.2 mg/dl and mean protein excretion was 6.1 ± 1.0 g/day. The incidence of FSGS increased from 19.3% (1986 – 1991) and 16.6% (1992 – 1997) to 58.5% in the period from 1998 – 2002. The increase occurred among black and Hispanic patients (33.3 – 79.2%) as well as white patients (12.5 – 51.5%). Black and Hispanic patients with PG presented for renal biopsy at a significantly younger age than white patients (p = 0.003), with mean age 37.5 ± 2.0 years vs. 50.3 ± 1.8 years. White FSGS patients were significantly older than white non-FSGS patients (mean age 56.4 ± 3.2 years vs. 48.0 ± 2.0 years, p = 0.03). Black and Hispanic FSGS patients were also older when compared to their non-FSGS counterparts (mean age 40.6 ± 2.8 years vs. 32.1 ± 2.0 years, p = 0.04). When patients were stratified by age (< 45 years and ³ 45 years), FSGS was the most common diagnosis in both age groups among black and Hispanic patients (55.1% and 88.8%) but only among older white patients (36.2%). Conclusions: The incidence of FSGS as a proportion of PG in our population has increased markedly in the most recent time period analyzed (1998 – 2002). The increase has occurred among both white and black and Hispanic patients. We also found that FSGS was most prevalent in patients ³ 45 years.Correspondence to:
J.L. Rosenstock, MD
130 E 77th Street, 5th Floor,
New York, NY 10021, USA
Email: jrosenstock@lenoxhill.net

Abstract

P. Meier, E. Dayer, P. Ronco and E. Blanc

¹Division of Nephrology, Department of Medicine, Hôpital de Sion,
²Division of Infectious Diseases and Immunology, Institut Central des Hôpitaux Valaisans, Sion, Switzerland, ³Institut National de la Santé et de la Recherche Médicale (INSERM) Unit ⁴⁸⁹, Hôpital Tenon (Assistance Publique-Hôpitaux de Paris) and Université Paris ⁶, France
Background/aim: Although CD4+ T cells are preactivated in patients with end-stage renal failure (ESRF), these patients present an impairment of T cell immune response, which is partly responsible for the higher incidence of infection in this population. The aim of the present study was to analyze the mechanisms underlying the altered function of activated CD4+ T cells in patients with ESRF. Methods: Thirty patients undergoing chronic hemodialysis (HD) and 20 patients with ESRF were compared with 15 sex- and age-matched controls. CD4+ T cell early activation (CD69, CD25), interleukin-2 (IL-2)/IL-2 receptor (IL-2R) system, and proliferation capacity of CD69+/CD4+ T cells were assessed ex vivo after blood draw sampling, in culture conditions and after phytohemagglutinin (PHA) stimulation. Results: Although the CD4+ T cell count was lower in chronic HD patients than in predialysis patients and controls (p = 0.007), CD4+ T cells showed a preactivation state as demonstrated by higher percentage of CD69+/CD4+ T cells and CD25+/CD4+ T cells in chronic HD patients compared with the other groups ex vivo. Furthermore, CD69+/CD4+ T cells from chronic HD patients spontaneously released more IL-2 (22 ± 6 pg/ml) than those from predialysis patients (12 ± 4 pg/ml, p = 0.005) and controls (5 ± 3 pg/ml, p = 0.001). However, after PHA stimulation, CD69+/CD4+ T cells from chronic HD patients expressed lower cell surface CD25 density, and were unable to show further activation. Indeed, these cells produced less IL-2 and released more soluble IL-2R, and correlatively with IL-2 production, they showed lower proliferation capacity compared with predialysis patients (p = 0.001) and controls (p < 0.001). They also displayed decreased responsiveness to exogenous human recombinant IL-2. The restoration of the PHA stimulation index of CD69+/CD4+ T cells from chronic HD patients in the presence of normal human serum as well as the decreased stimulation index of CD69+/CD4+ T cells from control subjects incubated with HD serum, strongly suggest that uremic toxins and mediators induced by HD affect the IL-2/IL-2R pathway. Conclusion: These findings demonstrate the presence, in chronic HD patients, and to lesser extent, in predialysis patients, of abnormally high proportion of spontaneously preactivated CD4+ T cells whose proliferation and further activation are blunted due to dysregulation of the IL-2/IL-2R system.

Correspondence to:
Dr. P. Meier

Division de Néphrologie

Centre Hospitalier Universitaire Vaudois (CHUV)

17, rue du Bugnon

1011 Lausanne, Switzerland
Email: Pascal.Meier@chuv.hospvd.ch

Abstract

N. Kuwae, J.D. Kopple and K. Kalantar-Zadeh

¹Division of Nephrology and Hypertension, Research and Education Institute, Harbor-UCLA Medical Center, Torrance, David Geffen School of Medicine at UCLA, Los Angeles, ²Department of Nephrology, Nakagami Hospital, Okinawa, Japan, ³UCLA School of Public Health, Los Angeles, and ⁴UC Berkeley, School of Public Health, Berkeley, CA, USA
Objectives: Lymphocyte percentage (LYM%), an independently measured value to reflect peripheral lymphocyte count and a possible nutritional marker, may be related to clinical outcome in maintenance dialysis (MHD) patients. Study design and setting: We examined the associations of the baseline white blood cell count (WBC) and LYM% with 12-month mortality and three measures of hospitalization in a cohort of 1,283 MHD patients from 10 outpatient DaVita dialysis clinics in Los Angeles County, as well as in a subcohort of 372 MHD patients with additional measures of inflammation, nutrition and comorbidity. Multivariate Cox and Poisson models that included 13 co-variates including case-mix features, dialysis dose, blood hemoglobin and serum albumin were explored. Results: Patients, aged 57.8 ± 15.2 years, included 49% men and 49% diabetics. Baseline WBC was 7,353 ± 2.427 per ml, and LYM% was 21.2 ± 7.3%. LYM% had significant correlations with “malnutrition-inflammation score” and inverse correlations with serum interleukin-6. The WBC and LYM% had significant but opposite predicting values for mortality and hospitalization, indicating that a high WBC and a low LYM% were each independently associated with increased mortality. After dividing each variable into four quartiles, only the highest WBC quartile (³ 8,500) but not the other middle two quartiles, predicted increased mortality. However, all three lower quartiles of LYM% vs. the highest quartile (based on quartile cutoffs of 16%, 20.3% and 25.5%) were significantly and progressively associated with greater risks of mortality and hospitalizations. The absolute lymphocyte count (LYM% times WBC/100) exhibited somewhat similar trends but its outcome predictability was not as strong as LYM%. Conclusions: A high WBC and a low LYM% are associated with significant increase in mortality and hospitalization in MHD patients. Lymphocyte percentage, compared to absolute lymphocyte count, appears to be a better nutritional and anti-inflammatory marker and a more sensitive predictor of mortality and hospitalization in MHD patients.Correspondence to:
K. Kalantar-Zadeh, MD, MPH, PhD

Assistant Professor of Medicine and Pediatrics

UCLA David Geffen School of Medicine

Division of Nephrology and Hypertension

Harbor-UCLA Medical Center

Harbor Mailbox 406

1000 West Carson Street

Torrance, CA 90509-2910, USA
Email: kamkal@ucla.edu

Abstract

A. Stragier and M. Jadoul

Department of Nephrology, Cliniques Universitaires St. Luc, Université Catholique de Louvain, Brussels, Belgium
Aims: The use of ultrapure dialysate decreases hemodialysis patients’ morbidity. Bacterial and endotoxin content of reverse osmosis (RO) water is usually lowered or eliminated by a combination of bacterial filtration and regular disinfection of the distribution. Whether bacterial filtration may be replaced by UV irradiation is unknown. Materials and methods: One, and subsequently two UV lamps were inserted in a complex RO water distribution circuit, devoid of bacterial filters. RO water bacterial content was checked weekly between RO water distribution disinfections. Results: With one UV lamp on the departure of the RO water circuit, bacterial results remained negative (< 1 cfu/ ml) till the second week after disinfection. Disinfection of the circuit was required every four weeks to comply with the AAMI Guidelines (< 200 cfu/ml). Failure of the lamp was followed by bacterial growth (up to 500 cfu/ml), promptly aborted after replacement of the failed lamp. Subsequent addition of a second UV lamp on the return line of the water circuit kept bacteria < 1 cfu/ml for up to five weeks. Endotoxin levels remained < 0.125 EU. Conclusions: UV irradiation preserves a low RO water bacterial/endotoxin content in the distribution line and is not associated with a measurable endotoxin increase.Correspondence to:
A. Stragier

Department of Nephrology

Cliniques Universitaires St-Luc

Université Catholique de Louvain

1200 Brussels, Belgium
Email: Andre.Stragier@pandora.be

Abstract

S.L. Hu and B.L. Jaber

¹Division of Renal Diseases, Department of Medicine, Rhode Island Hospital, Brown University School of Medicine, Providence, RI, and
²Division of Nephrology, Department of Medicine, Tufts New England Medical Center, Tufts University School of Medicine, Boston, MA, USA
Glomerular diseases associated with hepatitis C virus (HCV) infection are increasingly being recognized. Antiviral therapy with interferon-a (IFN-a) and ribavirin eradicate viral activity in a significant proportion of patients with chronic active hepatitis, often with amelioration of extrahepatic manifestations, including glomerular pathology. Unfortunately, adverse effects often preclude the use of IFN-a. We describe a patient with refractory nephrotic syndrome secondary to HCV-associated membranous nephropathy who sustained a complete remission following the initiation of ribavirin monotherapy. The existing literature on the association between these two disorders and therapy with ribavirin is reviewed.Correspondence to:
S.L. Hu, MD
Division of Renal Diseases
Department of Medicine
Rhode Island Hospital
Brown University School of Medicine
593 Eddy Street
Providence, RI 02903, USA
Email: shu@lifespan.org

Abstract

E. Jochum, V.M. Brandenburg, H.-P. Brodersen and U. Janssen

¹Department of Cardiology, Intensive Care Medicine and Nephrology, Krankenhaus St. Franziskus, Mönchengladbach, and
²Division of Nephrology and Immunology, University of Aachen, Germany
We report the first documented case of IgA nephropathy occurring after treatment of primary hyperparathyroidism. A 29-year-old man with a history of kidney stones and primary hyperparathyroidism underwent kidney biopsy for persistent proteinuria and microhematuria 18 months after resection of an ectopic parathyroid adenoma with subsequent normalization of serum calcium and parathyroid hormone levels. On ultrasound, renal intraparenchymal calcifications were noted. Renal biopsy revealed IgA nephropathy in addition to tubulointerstitial microcalcifications. The development of IgA nephropathy may have been influenced by hyperparathyroidism and/or its treatment. The case highlights the role of renal biopsy in patients with a history of kidney stones and abnormal urinary findings.Correspondence to:
Dr. U. Janssen
Innere Medizin II
Department of Cardiology, Intensive Care Medicine and Nephrology, Krankenhaus St. Franziskus, Kliniken Maria Hilf
Viersener Straße 450
41063 Mönchengladbach, Germany
Email: JanssenU@mariahilf.de

Abstract

R. Farah, R. Farah, M. Kolin, H. Cohen and B. Kristal

¹Department of Nephrology, Nahariya Hospital, B. Rappaport Faculty of Medicine, Technion, Nahariya, ²Department of Obstetrics and Gynecology, HaEmek Medical Center, Afula, ³Department of Nephrology, Nahariya Hospital, B. Rappaport Faculty of Medicine, Technion, Nahariya, ⁴Pathology Unit, Nahariya Hospital, B. Rappaport Faculty of Medicine, Technion, Nahariya, ⁵Nephrology and Hypertension Department, Nahariya Hospital, B. Rappaport Faculty of Medicine, Technion, Nahariya, Israel
Case report of a 70-year-old woman with the diagnosis of multiple myeloma and acute renal failure due to rhabdomyolysis (RDM) that was caused from the deposition of k light chain in muscle fibers. In addition, the deposition was found in the liver.Correspondence to:
R. Farah, M.D.
Nephrology Department
Western Galilee Hospital
Nahariya 22100, Israel
Email: raymondfarah@hotmail.com

Abstract

T. Liberek, A. Debska-Slizien, K. Preis, M. Swiatkowska-Freund, A. Liberek and B. Rutkowski

Departments of Nephrology, Transplantology and ¹Internal Medicine,
²Department of Obstetrics and Department of Pediatrics, Pediatric Gastroenterology and ³Oncology, Medical University, Gdansk, Poland
We present a successful pregnancy in a 37-year-old women with severe renal impairment due to medullary cystic disease. She presented five years earlier with hypertension and chronic renal failure with creatinine was 2.1 mg/dl (Ccr 35 ml/min). She had had two successful pregnancies in the past, nine and seven years earlier. Diagnosis of medullary cystic disease (MCD) was made based on typical ultrasound appearance, sodium wasting and acidosis out of the proportion to the degree of renal failure. Over the next 5 years, a slow progression of chronic renal failure was observed with creatinine reaching 5.1 mg/dl (Ccr 15,4 ml/min), shortly before she became pregnant in December 2001. Her hypertension remained well-controlled and serum creatinine decreased at the beginning of the second trimester to 3.7 mg/dl with subsequent increase toward the end of the pregnancy. She required increasing doses of erythropoietin and intravenous iron supplementation to maintain hemoglobin levels. The polyhydramnios developed necessitating five procedures of amnio reduction. She was not treated by dialysis. A boy weighing 1,600 g was delivered by cesarean section in the 35th week of gestation. The mother’s creatinine rose to 5.2 mg/dl (Ccr 15 ml/min) post partum and her renal function declined only slightly over the next 20 months. Our report illustrates that successful fetal and maternal outcome can be achieved even in cases of advanced renal failure preceding gestation. It appears that the type of renal disease influences the pregnancy course and outcome and thus should be considered in patient counseling and therapeutic decisions.Correspondence to:
Dr. T. Liberek
Department of Nephrology
Transplantology and Internal Medicine
Gdansk Medical University
Ul. Debinki 7
PL-80-211 Gdansk, Poland
Email: tlib@amg.gda.pl

Abstract

V.-C. Wu, K.-D. Wu, C.-C. Hung, S.-L. Lin, J.-W. Huang and P.-R. Hsueh

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Volume 63, No. 1/2005(January)