Volume 61, No. 2/2004(February)
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 Clinical Nephrology
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Originals
Renal impairment in patients with inflammatory bowel disease: association with aminosalicylate therapy?
Abstract
M.M. Elseviers, G. D'Haens, E. Lerebours, C. Plane, J.-C. Stolear, G. Riegler, G. Capasso, M. Van Outryve, P. Mishevska-Mukaetova, S. Djuranovic, P. Pelckmans and M.E. De Broe for the 5-ASA Study Group
1Department of Nephrology, University Hospital of Antwerp,
2Department of Gastro-Enterology, University of Leuven, Belgium,
3Department of Gastro-Enterology, Hospital of Rouen,
4Department of Gastro-Enterology, University Hospital Bethune, France, 5
Background: In recent years, several case reports have been published suggesting an association between the use of 5-aminosalicylic acid (5-ASA) in patients with inflammatory bowel disease (IBD) and the development of chronic tubulo-interstitial nephritis. Apart from lesions associated to 5-ASA treatment, however, it is clear that IBD itself may also induce renal impairment, albeit the frequency is unknown. Methods: During 1 year, all IBD patients seen at the outpatient clinic of 27 European centres of gastro-enterology were registered and screened for renal impairment controlling for a possible association with 5-ASA therapy. Patients were questioned about their medical and drug history and their IBD disease activity. Renal screening (calculated creatinine clearance) was performed at baseline, after 6 and 12 months. Results: Included patients (n = 1,529) had a mean age of 39 (range 14 – 98), 56% had Crohn’s disease, 42% ulcerative colitis and 2% indeterminate colitis. Half of the patients used 5-ASA during the study period. Decreased creatinine clearance was observed in 34 patients, among them 13 with chronic renal impairment. Comparing patients with and without renal impairment, no difference could be observed in 5-ASA consumption. In contrast, patients with renal impairment were significantly older, had a lower body mass index and showed a higher frequency of male sex, bowel resection and stoma. Conclusion: Although the association between 5-ASA therapy and chronic tubulo-interstitial nephritis is clearly described in several case reports, this prospective study came to the reassuring conclusion that renal impairment in IBD patients is not frequently observed and is rarely associated with 5-ASA therapy.
Originals
Primary glomerular diseases in Brazil (1979 – 1999): is the frequency of focal and segmental glomerulosclerosis increasing?
Abstract
M. Bahiense-Oliveira1, L.B. Saldanha2, E.L. Andrade Mota3, D. Oliveira Penna1, R. Toledo Barros1 and J.E. Romão-Junior1
Divisions of 1Nephrology and 2Pathology, Hospital das Clínicas, University of São Paulo, São Paulo, Brazil, Instituto de Saúde Coletiva, Universida de Federal da Bahia, Salvador, Brazil
Aims: Different patterns of glomerulonephritis (GN) are reported from all over the world and the occurrence of primary GN is changing in the course of time. We report the frequencies of primary GN in a major teaching hospital in Brazil, from 1979 – 1999. Methods: The case files of renal biopsies of primary GN were reviewed. The included patients were > 14 years of age, with native kidneys, and the specimens were examined with at least light and immunofluorescence microscopy. We excluded biopsy results of patients with any kind of known secondary glomerular involvement. Differences in proportions of diagnoses between the periods over time were evaluated using Chi-square test for trend. Results: We considered 943 patients for the analysis. Focal and segmental glomerulosclerosis (FSGS) was the most common lesion (n = 279), followed by membranous GN (n = 140), membranoproliferative type I GN (n = 109) and IgA nephropathy (n = 109). FSGS (32.1%) was the most frequent diagnosis among nephrotic patients whereas IgAN (29.4%) predominated in non-nephrotic ones. The occurrence of FSGS increased from the earlier to the later periods: 22.3% (1979 – 1983), 23.7% (1984 – 1988), 35.7% (1989 – 1993), 33.9% (1994 – 1999), p < 0.05. The increase in frequency of FSGS was proportionally higher in non-nephrotic patients and FSGS became as common as IgA nephropathy in this group (31.6% and 28.0%, respectively) from 1994 – 1999. Conclusions: FSGS was the most common pattern of primary glomerulonephritis and its relative frequency seems to be increasing in biopsied patients over time. The reasons for this behavior are unclear and warrant further investigations.
Originals
Time course of serial cystatin C levels in comparison with
serum creatinine after application of radiocontrast media
Abstract
H. Rickli1, K. Benou2, P. Ammann3, Th. Fehr2, H.P. Brunner-La Rocca1, H. Petridis2, W. Riesen3 and R.P. Wüthrich2
Departments of 1Cardiology, 2Nephrology, and 3Clinical Chemistry, Kantonsspital, St. Gallen, Switzerland
Background: The delayed increase of creatinine after radiocontrast application is a potential reason for overlooking radiocontrast nephrotoxicity. Cystatin C may be more useful to rapidly assess a decrease in glomerular filtration rate (GFR). We compared cystatin C and creatinine to examine their kinetics after application of radiocontrast media. Patients and methods: Forty-one patients (60.8 ± 8.8 years, 68% males) with normal to subnormal GFR scheduled for coronary angiography (27% with angioplasty), were studied for serum cystatin C and creatinine levels before, 5 h, 24 h and 48 h after angiography. Furthermore, a1-microglobulin was checked for evidence of tubular damage. Results: At 5 hours after angiography, there was no significant change compared to baseline in either serum creatinine nor cystatin C. In comparison with the value immediately before coronary angiography, the increase of cystatin C achieved a maximum at 24 h after the application of the contrast agent (+7.2%). Within 48 h, cystatin C decreased to the level before angiography. Serum creatinine increased at 24 h (+7.7%) and continued to increase at 48 h (+11.3%). Conclusion: Cystatin C increases earlier after radiocontrast application compared with creatinine. Therefore, cystatin C needs to be investigated as a potential early marker for nephrotoxicity, especially in the upcoming setting of short-time hospitalizations for coronary angiographies and interventions. Thus, further studies in patients with renal failure undergoing radiocontrast application are warranted to assess the usefulness of cystatin C in respect of an earlier detection of radiocontrast nephrotoxicity.
Originals
Predictive value of interleukins 6, 8 and 10, and low HLA-DR expression in acute renal failure
Abstract
A. Åhlström1, M. Hynninen1, M. Tallgren1, P. Kuusela2, M. Valtonen3, R. Orko1, S. Siitonen2, O. Takkunen1 and V. Pettilä1
1Department of Surgery, Division of Anesthesiology and Intensive Care Medicine, 2Division of Clinical Microbiology, HUCH Laboratory Diagnostics, and 3Department of Internal Medicine, Division of Infectious Diseases, Helsinki University Hospital, Helsinki,
Aims: HLA-DR expression and plasma levels of pro- and anti-inflammatory cytokines (IL-6, IL-8 and IL-10) and their predictive value concerning survival of critically ill systemic inflammatory response syndrome (SIRS) patients with and without acute renal failure (ARF) were evaluated. Material: A total of 103 consecutive adult patients with SIRS from 2 university hospital intensive care units participated in the study. Method: Laboratory data for all patients were prospectively collected on the day of admission and 2 days thereafter. Patients with acute renal failure (ARF) and non-ARF patients were compared by Mann-Whitney U-test. Independent predictors of mortality were tested using forward stepwise logistic multiple regression analysis. The discriminative power of different variables was tested using receiver operating characteristic (ROC) curve analysis. Results: ARF developed in 36 patients (35%). ARF patients showed significantly lower HLA-DR expression and higher plasma levels of IL-6, IL-8 and IL-10 than non-ARF patients. In ARF, moderate discriminative power in predicting survival was observed for day 2 IL-6 and IL-10 plasma levels (AUCs 0.703 and 0.749, respectively). Conclusions: We found no clinically significant discriminative power in predicting survival of ARF patients for monocyte HLA-DR expression or cytokine plasma levels. Therefore, our results do not support the use of HLA-DR expression or cytokine plasma levels for that purpose.
Originals
Comparison of the severity of illness scoring systems for
critically ill cirrhotic patients with renal failure
Abstract
Y.-C. Chen, M.-H. Tsai, Y.-P. Ho, C.-W. Hsu, H.-H. Lin, J.-T. Fang, C.-C. Huang and P.-C. Chen
1Division of Critical Care Nephrology, and 2Division of Gastroenterology, Chang Gung Memorial Hospital, Chang Gung University, Taipei, Taiwan
Background: Mortality rates of cirrhotic patients with renal failure admitted to the medical intensive care unit (ICU) are high. End-stage liver disease is frequently complicated by disturbances of renal function. This investigation is aimed to compare the predicting ability of acute physiology, age, chronic health evaluation II and III (APACHE II and III), sequential organ failure assessment (SOFA), and Child-Pugh scoring systems, obtained on the first day of ICU admission, for hospital mortality in critically ill cirrhotic patients with renal failure. Methods: Sixty-seven patients with liver cirrhosis and renal failure were admitted to ICU from April 2001 – March 2002. Information considered necessary for computing the Child-Pugh, SOFA, APACHE II and APACHE III score on the first day of ICU admission was prospectively collected. Results: The overall hospital mortality rate was 86.6%. Liver disease was most commonly attributed to hepatitis B viral infection. The development of renal failure was associated with a history of gastrointestinal bleeding. Goodness-of-fit was good for SOFA, APACHE II and APACHE III scores. The APACHE III and SOFA models reported good areas under receiver operating characteristic curve (0.878 ± 0.050 and 0.868 ± 0.051, respectively). Conclusion: Renal failure is common in critically ill patients with cirrhosis. The prognosis for cirrhotic patients with renal failure is poor. APACHE III and SOFA showed excellent discrimination power in this group of patients. They are superior to APACHE II and Child-Pugh scores in this homogenous group of patients.
Originals
Evaluation of tubulointerstitial injury by Doppler ultrasonography in glomerular diseases
Abstract
T. Sugiura, A. Nakamori, A. Wada and Y. Fukuhara
Department of Internal Medicine, Osaka National Hospital, Osaka, Japan
Aims: While Doppler ultrasonography is used commonly in various renal diseases, its clinical value in diagnosis of renal parenchymal diseases, especially glomerular diseases, remains controversial. We investigated whether Doppler ultrasonography in glomerular diseases could discriminate tubulointerstitial lesions, which correlated closely with long-term prognosis for renal function. Methods: Sixty patients with primary or secondary glomerular diseases were examined by Doppler ultrasonography immediately before renal biopsy. The resistive index was calculated, as was the atrophic index (a newly proposed parameter defined as renal sinus length/renal length). These were compared with histologic changes in biopsy specimens. Results: Receiver operator characteristic analysis showed a resistive index of 0.65 to be the optimal for discriminating tubulointerstitial changes with specificity of 100% and sensitivity of 57.1%. Tubulointerstitial injury scores were significantly higher in patients with resistive indices exceeding 0.65 than in patients with a lower value. An atrophic index of 0.70 was also shown to be optimal with specificity 100% and sensitivity 61.9%. In combination, the 2 indices showed improved sensitivity; when the patients were divided into groups where both resistive and atrophic indices were normal (respectively £ 0.65 and £ 0.70) or where either or both were high, sensitivity rose to 85.7%, while specificity remained 94.4%. Conclusions: In combination, the resistive and atrophic indices discriminated tubulointerstitial injury in glomerular diseases with high specificity and sensitivity.
Originals
The presence of erythropoietin receptors in the human
peripheral nervous system
Abstract
K. Hassan, B. Gross, W. Simri, I. Rubinchik, H. Cohen, J. Jacobi, S.M. Shasha and B. Kristal
1Nephrology and Hypertension Department, 2Neurology Department and 3Pathology Department, Western Galilee Hospital, Nahariya, Israel
Erythropoietin (EPO) is a well-known hematopoietic factor and a major determinant of tissue oxygenation. EPO receptors have been identified on a wide variety of non-erythroid cell types including human central nervous system and peripheral nervous system of animal models. The presence or function of EPO receptors in human peripheral nervous system is unknown. By examining nerve segments from radicular and autonomic nerves using immunohistochemical methods, we demonstrated the presence of EPO receptors on myelin sheath of radicular nerves in the human peripheral nervous system.
Originals
Measurement of fiber bundle volume in reprocessed dialyzers
Abstract
S.S. Narsipur
Department of Medicine, SUNY Upstate Medical University, Syracuse, New York, USA
Background: Fiber bundle volume (FBV) is an important determinant of dialyzer re-use efficiency. This measurement is performed after the dialyzer has been pressure cleaned and may underestimate the degree of clotted fibers a patient actually encounters while on dialysis. Methods: Real-time online measure of FBV has been validated using an ultrasound dilution method and the Transonic HD01 monitor (Ithaca, NY, USA). Thirty-one stable chronic hemodialysis patients were studied during the first hour and then during the last 30 minutes of a typical dialysis session. Ultrasound velocity curves using a saline bolus were recorded by flow dilution sensors placed directly on the blood tubing using methods described previously. Blood volume within the dialyzer compartment was determined using a mathematical extrapolation of the measured transit time for a bolus of saline to pass through the dialyzer. These data were compared to FBV obtained using a Seartronics DRS4 (Fresinius, Walnut Creek, CA, USA) reprocessing machine both before and after the same dialysis session. Results: At onset of treatment mean FBV by ultrasound was 100.0 ± 2.7 ml and was unchanged at the end of the session at 100.0 ± 3.1 ml (p = 0.49). Before a dialysis session, mean FBV measured on the DRS4 reprocessing machine was 123.5 ± 2.1 ml and was unchanged following cleaning after dialysis at 121.7 ± 2.0 ml (p = 0.20). The correlation coefficient between methods was 0.78. Conclusions: FBV did not change during a dialysis session using an online real-time measure. The results of this study do not support concerns that hemodialysis patients may experience considerably less efficient dialysis than standard FBV determination would suggest due to undetected clotting.
Originals
Improving the delivery of continuous renal replacement therapy using regional citrate anticoagulation
Abstract
R. Swartz1, D. Pasko2, J. O’Toole1 and B. Starmann1
1Department of Internal Medicine, Division of Nephrology, and
2College of Pharmacy, University of Michigan, Ann Arbor, Michigan, USA
Aims: Regional citrate anticoagulation during acute renal replacement therapy (RRT) effectively prevents extracorporeal thrombosis and avoids bleeding risk. There have been a number of citrate anticoagulation protocols published; but a simple and predictable scheme with standardized components and procedures, as well as clearly defined citrate pharmacokinetics, is needed for continuous RRT (CRRT) that is now used frequently in the critical care setting. The present study sets forth methodology with standardized blood flow and dialysate composition, and with citrate and calcium infusions that are quantitatively linked to extracorporeal blood flow rate – a predictable and easily replicated CRRT paradigm. Materials and methods: CRRT using continuous venovenous hemofiltration with dialysis (CVVHD) was standardized using 150 – 200 ml/min blood flow, calcium-free dialysate with only moderate sodium (135 mEq/l) and bicarbonate (28 mEq/l) concentrations, and ultrafiltration limited to that needed for overall fluid balance in the intensive care unit. Citrate infusion (ACD-A solution) into the extracorporeal blood and calcium repletion in blood returned to the patient were proportional to blood flow. Anticoagulation was accomplished by keeping extracorporeal ionized calcium below 0.4 mM/l. Filter performance, citrate removal and changes in calcium, sodium and alkali were evaluated longitudinally. Results: CVVHD using this protocol delivered urea clearance exceeding 2 l/h (48 l/d) when filter function was sustained. Filter longevity was markedly improved using citrate when compared with standard heparin anticoagulation, and nursing time spent on initiating and trouble-shooting CRRT was approximately halved using this protocol. Sieving coefficients for urea, creatinine and citrate were approximately 0.9 and were sustained through nearly 3 days of filter use. Citrate clearance and removal were quantitatively linked to dialysate and ultrafiltration flow, resulting in 35 – 50% direct removal of the citrate-calcium chelate and reduced systemic citrate load. Serum tonicity and acid-base status were not problematic. The only notable side effect was modest calcium accumulation that necessitated reduction in calcium repletion rate. Conclusions: CVVHD is well suited to regional citrate anticoagulation. The present protocol is straightforward and predictable, with minor metabolic consequences that can be anticipated and adjusted. These results commend regional citrate anticoagulation to wider application.
Case reports
Membranous glomerulonephritis associated with hepatitis C virus infection: case report and literature review
Abstract
Y. Uchiyama-Tanaka, Y. Mori, N. Kishimoto, A. Nose, Y. Kijima, T. Nagata, Y. Umeda, H. Masaki, H. Matsubara and T. Iwasaka
Renal Division and 2Cardiovascular Center, Department of Medicine II, Kansai Medical University, Osaka, Japan
We describe the case of a 51-year-old man with hepatitis C virus (HCV) infection and a 3-month history of facial edema. Laboratory tests upon admission for renal biopsy showed normal renal function and normocomplementemia. Serum HCV antibody (Ab) and cryoglobulin were positive. Renal biopsy specimens showed features of membranous glomerulonephritis. The likely cause was immune complex-mediated glomerulonephritis associated with HCV infection. Reports of similar cases in the literature show the normocomplementemia and negative or slightly positive cryoglobulins observed in our case as well as seropositivity for circulating immune complexes containing HCV RNA. In our case, electron microscopic examination of the subepithelial glomerular lesions revealed massive virus-like particles within unusual multilayers of electron-dense deposits (EDDs), suggesting the existence of HCV in the glomeruli. In the addition to the unique histopathological feature the presence of La/SS-B antibody in his serum indicated an abnormal immune response associated with HCV. We advise him to undergo the therapy with new type of IFN such as pegIFN-a2a and/or anti-viral agent like ribavirin to achieve clinical and histopathological improvement.
Case reports
Multiple bilateral fibroadenomas of the breasts
requiring mastectomy in a renal transplant patient
Abstract
N. Kanaan and E. Goffin
Department of Nephrology, Université Catholique de Louvain, Brussels, Belgium
Fibroadenomas of the breast have been reported in female renal graft recipients and associated with the use of cyclosporin A (CsA). We report the case of a young patient given CsA who developed multiple bilateral fibroadenomas of the breasts 3 years after renal transplantation, leading to bilateral mastectomy. We discuss the association of CsA with fibroadenomas, the mechanisms by which the drug can act and review the literature. Based on these observations, an early conversion from CsA to tacrolimus should be considered; further observations are needed to assess the reversibility of the breast(s) lesions after such immunosuppressive regimen switch.
Case reports
Pure red-cell aplasia induced by anti-erythropoietin antibodies in peritoneal dialysis
Abstract
F. Coronel1, M. García-Mena1 and R. Martínez2
1Department of Nephrology, and 2Department of Hematology,
Hospital Clínico San Carlos, Madrid, Spain
There have been several recent reports of pure red-cell aplasia (PRCA) mediated by anti-erythropoietin antibodies (AEA) in patients with chronic renal failure treated with recombinant human erythropoietin (EPO). Among the factors thought to trigger this mechanism is the subcutaneous administration of EPO. Despite this being the normal route of administration in patients undergoing peritoneal dialysis (PD), to date there has only been 1 described case of PRCA due to AEA in PD. Herein, we report such a case involving a patient in whom a diagnosis of anemia due to PRCA was particularly difficult to make because of concomitant rectal bleeding.
Letters to the Editor
Hyperparathyroid hypercalcemic crisis in a patient on calcium and vitamin D supplementation
Abstract
R.J.A. Sims, D.J. Hosking, M.J.D. Cassidy and I. Dasgupta
Letters to the Editor
Effect of vitamin B12 on homocysteine plasma concentration in hemodialysis patients
Abstract
I. Baragetti, S. Furiani, V. Dorighet, E. Corghi, F. Bamonti Catena and G. Buccianti
