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Abstract

C. Schmidt¹, J. Tomiuk², E. Botzenhart¹, U. Vester³, M. Halber⁴, A. Hesse⁴, C. Wagner⁵, S. Lahme⁶, F. Lang⁷, K. Zerres¹, T. Eggermann¹ and members of the APN Arbeitsgemeinschaft für Pädiatrische Nephrologie: H. Bachmann, A. Bökenkamp, M. Fischbach, S.

¹Institute of Human Genetics, Technical University of Aachen,
²Institute of Anthropology and Human Genetics, Tübingen,
³Children’s Hospital, University of Essen, ⁴Department of Experimental Urology, University of Bonn, Germany, ⁵Institute of Physiology, University of Zürich, Switzerland, ⁶Department of Urology, University of Tübingen, and ⁷Institute of Physiology, University of Tübingen, Germany
Cystinuria is a hereditary disorder of cystine and dibasic amino acid transport across the luminal membrane of renal tubules and intestine, resulting in recurrent nephrolithiasis. While mutations in the SLC3A1 gene cause type I cystinuria, patients with non-type I cystinuria carry mutations in the SLC7A9 gene. Both gene products form the renal amino acid transporter rBAT/b0,+AT affected in cystinuria. In the present study a total of 59 patients with different ethnic background were screened for sequence variations in SLC7A9, out of these 32 were of German origin. For determination of allele frequencies of detected polymorphisms, 58 healthy German controls were investigated. Molecular-genetic analysis was performed using single-strand conformation polymorphism analysis, restriction assays and sequencing. Allele frequencies were analyzed statistically for the detected polymorphisms. In addition to the 6 already known variants we identified 7 new polymorphisms. Statistical analyses showed a significantly different distribution of alleles between German patients and German controls in case of the polymorphisms c.147C>T (exon 2), c.386C>T (exon 3), IVS3+22T>G, c.584C>T (exon 4), c.610T>C (exon 4), c.692C>T (exon 5), c.852C>A (exon 6) and c.872C>T (exon 6). In summary, our results show that cystinuria is a complex disease which is not only caused by mutations in SLC7A9 and SLC3A1, but also influenced by other modifying factors such as variants in SLC7A9.

Abstract

N. Takahashi, S. Yuasa, M. Fukunaga, T. Hara, K. Moriwaki, T. Shokoji, H. Hitomi, H. Fujioka, H. Kiyomoto, Y. Aki, M. Hirohata, K. Mizushige and M. Kohno

¹Second Department of Medicine, Kagawa Medical University, ²Kagawa Prefectural College of Health Science, ³Department of Integrated Medicine, Kagawa Medical University, and ⁴Mitoyo General Hospital, Kagawa, Japan
Background: Hemodialysis patients very often suffer from malnutrition with net loss of body muscle and fat stores. Since protein-calorie malnutrition has been considered to be highly associated with increased morbidity and mortality, it is important that the nutritional status is evaluated accurately and that long-term evaluation of the nutritional status is performed to obtain good outcome. Patients and methods: Forty-six patients (28 men and 18 women) undergoing maintenance hemodialysis were studied. Nutritional status of the patients was examined by dual-energy X-ray absorptiometry (DXA) and anthropometry measurements after a hemodialysis session and 4 years after the initial measurement. Results: Percent fat, the ratio of body fat (BF) to weight, determined by DXA correlated positively with body mass index (BMI) calculated from weight and height. There was also a significant positive correlation between lean body mass (LBM) determined by DXA and arm muscle circumference (AMC) calculated using the anthropometric method. In the study period of 4 years, LBM and bone mineral content (BMC) observed at the end point were significantly lower than those at the start. In contrast, BF and %fat at the end point were significantly higher as compared with those at the initial measurement. Conclusion: These results indicate that DXA is a reliable method for body composition analysis in chronic hemodialysis patients. Because the detection of early alterations in body composition may provide an early indication of the development of malnutrition, serial evaluation of body composition using DXA should be valid for assessment of the nutritional status.

Abstract

S. Simsek, A.L. Oen, E.F.I. Comans, J.J.M. v.d. Hoeven and J. Zijlstra

¹Department of Internal Medicine, ²Department of Radiology, ³Department of Nuclear Medicine, “Vrije Universiteit” Medical Centre, and ⁴Department of Internal Medicine, Ziekenhuis Amstelveen, Amstelveen, The Netherlands
Acute renal failure (ARF) as a consequence of non-Hodgkin lymphoma infiltration of the kidneys (LIK) is an uncommon complication of non-Hodgkin lymphoma. In literature, ARF due to LIK is reported in progressive disease. A case of non-oliguric acute renal failure secondary to relapse of large B cell non-Hodgkin lymphoma primarily localized in the mediastinum is reported. LIK of both kidneys was diagnosed by ultrasonography, computer tomography scan and 18-fluorodeoxyglucose positron emission tomography. No other causes for renal failure were found. The prognosis of renal involvement in relapsed non-Hodgkin lymphoma is poor, as is demonstrated by our case.

Abstract

H.H. Malluche, H. Mawad, D. Trueba and M.-C. Monier-Faugere

Division of Nephrology, Bone and Mineral Metabolism, Department of Internal Medicine, University of Kentucky, Lexington, KY, USA
Renal osteodystrophy may present with low, normal, or high bone turnover. An ideal parathyroid hormone (PTH) assay should discriminate between the bioactive whole PTH-(1-84) molecule and PTH fragments, including the PTH-(7-84) fragment. Most dialysis patients have “intact” PTH (iPTH) levels between 65 and 450 pg/ml, which are poorly predictive of bone turnover state, making the iPTH test of limited value for bone turnover prediction. iPTH levels higher than 500 pg/ml can be observed in some dialysis patients with low bone turnover, while iPTH levels as low as 100 pg/ml have been found in patients with bone turnover above normal, indicating the standard second generation iPTH assay is not a reliable sole indicator of bone turnover. The whole PTH immunoradiometric assay, a third generation assay, uses a detection antibody that recognizes antigenic determinants at the extreme aminoterminal (1-4) end of the PTH molecule, making the assay specific for biologically active whole PTH-(1-84). Comparing results using the whole PTH and iPTH assays, the PTH-(7-84) level is indirectly determined and the PTH-(1-84)/PTH-(7-84) ratio can be calculated. It was shown that PTH-(7-84) inhibits the calcemic effect of PTH-(1-84) and its stimulatory effect on bone turnover. In the interpretation of results using the PTH-(1-84)/PTH-(7-84) ratio, it must be taken into consideration that second generation “intact” PTH assays have different cross-reactivity with PTH-(7-84). Therefore, when comparing or analyzing PTH-(1-84)/PTH-(7-84) ratios, the employed PTH assays must be identical. The whole PTH assay and the PTH-(1-84)/ PTH-(7-84) ratio allow more meaningful interpretation of PTH trends, and offer a non-invasive means to more accurately diagnose bone disease in this population.

Abstract

R.B. Mazess and L. Elangovan

¹Bone Care International, Middleton, and ²Professional Practice Group, Darlington, WI, USA
Background/methods: We examined 21 clinical trials (16 articles and 5 abstracts) that compared intravenous (i.v.) and oral vitamin D analogs for the treatment of secondary hyperparathyroidism in hemodialysis patients. Nearly all the studies had severe limitations, especially study size. Only 2 studies utilized more than 25 patients per treatment arm; 11 of the 16 articles and 4 of the 5 abstracts had less than 15 patients per arm. Calcitriol and/or a-calcidol were studied in 20 trials of the 21 studies (15 of the 16 articles) while 1 article examined doxercalciferol. Results: No difference of efficacy between i.v. and oral dosing was found in 10 of the 15 articles in which efficacy was assessed. The i.v. route provided significantly faster suppression of elevated parathyroid hormone (PTH) and/or a greater degree of suppression in 5 of 15 applicable articles, but in 2 of these 5 studies the i.v. dose was substantially greater than the oral dose. Side effects, chiefly hypercalcemia, were noted in half of the articles. Six of 9 articles with detailed results found no significant difference; only 2 found significantly increased hypercalcemia with oral dosing, and 1 found significantly increased hypercalcemia with i.v. dosing. Only 3 articles reported on hyperphosphatemia and no difference was found for mode of administration. One factor influencing 19 of the 21 comparisons was the use of oral doses that were therapeutically equivalent to about half or less the i.v. dose given the lower bioavailability of oral D hormones. One larger study (70 patients) that compared equipotent dosing of the 2 administration routes found 4 times more hypercalcemia using oral than i.v. dosing (p < 0.001). Another factor complicating interpretation is that the treatment periods were short, with half being 16 weeks or less and only 2 lasting 36 weeks. Conclusion: Conclusions about the comparative efficacy and safety of the 2 administration routes require larger studies of longer duration that utilize therapeutically equivalent doses.

Abstract

M.S. Sever, E. Erek, R. Vanholder, G. Kantarci, M. Yavuz, A. Turkmen, H. Ergin, M.Y. Tulbek, M. Duranay, G. Manga, S. Sevinir and N. Lameire

For the Marmara Earthquake Study Group: ¹Department of Nephrology, Istanbul School of Medicine, Istanbul, ²Department of Nephrology, Cerrahpasa School of Medicine, Istanbul, ³Renal Division, University Hospital, Ghent, Belgium, ⁴Department of Nephrology, Marmara School of Medicine, Istanbul, ⁵Department of Nephrology, Uludag School of Medicine, Bursa, ¹Department of Nephrology, Istanbul School of Medicine, Istanbul, ⁶Department of Nephrology, Goztepe Social Security Hospital, Istanbul, ⁷Gulhane Military Hospital, Renal Division, Istanbul, ⁸Department of Nephrology, Etlik Social Security Hospital, Ankara, ⁹Department of Nephrology, Sisli Etfal State Hospital, Istanbul, ¹⁰Department of Nephrology, Bursa Social Security Hospital, Bursa, Turkey, and ¹¹University Hospital, Ghent, Belgium
Background: Hyperkalemia is a major cause of mortality in the patients who suffer from crush syndrome in the aftermath of major earthquakes. The aim of this study is to investigate the frequency and effects of hyperkalemia in the 639 victims of catastrophic Marmara earthquake that struck northwestern Turkey, in August 1999. Patients and methods: Within the first week of disaster, questionnaires were sent to 35 reference hospitals that treated the victims. Information on serum potassium which was provided in 595 out of 639 questionnaires was submitted to analysis. Results: In the patients who were admitted within the first 3 days of the disaster (n = 401) serum potassium was 5.4 ± 1.3 mEq/l, which was higher than in those admitted thereafter (n = 171) (4.5 ± 1.1 mEq/l) (p = 0.02). Considering the whole series, males (p = 0.01), patients needing dialysis support (p < 0.001) and non-survivors (p = 0.001) were characterized by higher serum potassium at admission. Seventy patients’ serum potassium was above 7 mEq/l, while 22 patients were hypokalemic (< 3.5 mEq/l). Admission potassium correlated with many clinical and laboratory variables indicating the severity of the trauma, and a logistic regression model with clinical and laboratory parameters upon admission, revealed potassium as the most significant predictor of dialysis needs in the victims admitted within the first 3 days (p = 0.008, OR = 3.33). Among the victims who were admitted to hospitals 1 week after the disaster, 8 had serum potassium levels above 6.5 mEq/l; among 4 of them were complicated by hyperkalemia even higher than 7.5 mEq/l. These findings undeline the importance of hyperkalemia during clinical course. Conclusion: The most important and fatal medical complication in crush syndrome patients is hyperkalemia. Risk of fatal hyperkalemia continues even after hospitalization. Empirical therapy at the scene is indicated especially in male victims with severe soft tissue traumas. Early detection and treatment of hyperkalemia may improve the final outcome of renal disaster victims.

Abstract

A. Ersoy¹, M. Yavuz¹, M. Usta¹, I. Ercan², I. Aslanhan¹, M. Güllülü¹, E. Kurt¹, G. Emir¹, K. Dilek¹ and M. Yurtkuran¹

Departments of ¹Nephrology and ²Biostatistics, Uluda
Background: We reviewed medical records of dialyzed patients admitted to our hospital after the Marmara earthquake and evaluated the factors affecting mortality in survivors and non-survivors according to the survival times. Patients and methods: Crush syndrome (CS) was diagnosed in 110 patients. Dialysis treatment was initiated in 60 patients; 21 of all died. The patients were divided into 2 groups which consisted of 39 survivors (Group A, 25 male, 14 female, mean age: 31 ± 2.2 years) and 21 non-survivors (Group B, 9 male, 12 female, mean age: 27 ± 3.0 years). Victims treated by any form of renal replacement therapy, including daily or intermittant hemodialysis and/or continuous venovenous hemodiafiltration. Clinical and laboratory findings were recorded regularly. Statistical analysis was performed with Kaplan-Meier method, log rank test and Cox regression analysis for the survival functions. Results: APACHE II scores were 13.5 ± 0.5 for Group A and 13 ± 0.9 for Group B. Dialysis support was started to patients in Group A in a mean period of 2.8 ± 0.2 days and in Group B in a mean period of 3.7 ± 0.6 days after the earthquake (p > 0.05). The most frequent site of trauma was lower extremity (61.5%) and upper + lower extremities (23%) in Group A, and lower extremity (38.1%) and trunk + lower extremity (23.8%) in Group B. The frequencies of abdominal trauma, pelvic fracture and thoracic trauma in Group B were 23.8%, 19% and 14.2%, respectively. Multiple trauma was more frequent in Group B than in Group A (42.8% vs 2.5%). The rates of fasciotomy, amputation and surgery were similar in both groups. The frequency of sepsis was higher in non-survivors. In our center, the overall mortality rate was 8%, mortality rate in CS was 21% and in dialyzed patients it was 35%. Mortality was mainly associated with sepsis. Survival periods (52.3 ± 4.0 days) in Group A were longer than in Group B (17.3 ± 2.5 days). With Cox regression analysis, the parameters such as systolic hypotension on admission, female gender, high serum peak creatine kinase (> 20,000 U/l) and multiple trauma including thoracic and abdominal regions, were factors increasing risk of mortality. Conclusion: As a result, sepsis, multiple trauma and severe crush injury were the main factors increasing mortality risk in dialyzed injuries after the earthquake.

Abstract

U. Anandh, S. Renuka, S. Somiah and L. Vincent

Department of Nephrology, St. John’s Medical College Hospital, Bangalore, India
Aim: To study epidemiology, laboratory parameters, outcome and factors determining outcome of patients presenting with acute renal failure in our hospital. Materials and methods: A prospective study between December 1997 – December 1999 in which all patients presenting with acute renal failure were included. Demographics, laboratory parameters, etiology, outcome and prognostic factors determining outcome were studied. Results: 642 patients were part of the study. The predominant underlying cause for ARF was sepsis (153/642); overall mortality was 26.5%. Patients who had sepsis were admitted in the ICU, and patients with oliguria had poorer outcome. Conclusion: Sepsis continues to be the predominant cause of ARF. Overall mortality of our patients is better, because of the case mix, a large percentage of patients had acute gastroenteritis as a cause of CRF.

Abstract

O. Bakoush, O. Torffvit, B. Rippe and J. Tencer

Department of Nephrology, Lund University Hospital, Sweden
Renal function in proteinuric glomerular diseases correlates to the changes in urine IgM but not to the changes in the degree of albuminuria. Background: Albuminuria is believed to correlate to the progression of renal failure in glomerular diseases. Nevertheless, many patients with glomerular disorders maintain their renal function despite persistent albuminuria. In previous studies, we found that the baseline urine excretion of IgM, rather than the degree of albuminuria, predicts the renal outcome in glomerulopathies. In the present study, we examine correlations between changes in the content and in the amount of urine proteins and renal survival during a follow-up time of 3.5 years. Methods: An observational study of a mean of 44 (± 3.6) months was conducted in 37 proteinuric patients (21 males and 16 females) with biopsy-verified primary glomerular disease. The patients were subdivided, according to the findings at the end of the study, into 3 groups, 1 group with decreasing albuminuria (by more than 50%), 1 group with persisting albuminuria and low (< 0.04 mg/mmol creatinine) urinary IgM excretion and 1 group with persisting albuminuria and with high (³ 0.04 mg/mmol) urinary IgM excretion. Results: All patients that showed remission of albuminuria had also low IgM excretion at the end of the study. All these patients, except 1, maintained their renal function. Patients with persistent albuminuria and high urinary IgM excretion showed a decrease in the glomerular filtration rate (GFR) of a mean of 9.6 ml/min/year compared to a mean GFR increase by 1.5 ml/min/year in patients with low IgM excretion and the same degree of albuminuria (p < 0.01). Seven out of the 9 patients in the former group fall in GFR by more than 5 ml/min/year compared to only 1 of the 10 patients in the latter group. Furthermore, the GFR alterations that occurred during follow-up time correlated in a higher degree to the changes in urinary IgM excretion (r = 0.6, p < 0.01) than to the changes in the degree of albuminuria, (r = 0.4, p < 0.05). A stepwise regression analysis indicated that increased urine IgM excretion is a strong predictor of the GFR decline (r = 0.73, p < 0.001). Conclusion: High urinary IgM excretion correlates to decreased GFR in primary glomerular diseases regardless of the degree of albuminuria. In parallel, low urinary IgM excretion indicates beneficial prognosis in these diseases. Since IgM passes the glomerular barrier entirely through large shunts or defects in the glomerular capillary wall, decreased urine content of IgM might be considered as a sign of recovery in the glomerular damage.

Abstract

A. Panesar and R. Agarwal

Department of Medicine, Division of Nephrology, Indiana University and RLR VA Medical Center, Indianapolis, IN, USA
Background: The kidneys may account for up to 20% of resting energy expenditure (REE), but there is controversy regarding the relationship between severity of renal impairment and REE. Furthermore, reduction in protein intake is associated with declining glomerular filtration rate (GFR) that contributes to malnutrition. If a selective aversion to protein intake or a global reduction in food intake takes place is not known. Methods: To define the relationship between REE and its relationship to GFR, we measured REE with indirect calorimetry, GFR with iothalamate clearance, and body composition with creatinine kinetics and skin-fold measurements in 16 patients with mild to moderate renal failure due to type 2 diabetes mellitus (n = 12) or glomerulonephritides (n = 4). Results: In univariate analysis, age, weight, height, body mass index, lean body mass, urine urea nitrogen but not hemoglobin or albumin correlated with REE. In multivariate analysis, lean body mass emerged as the strongest predictor of REE followed by GFR. A lower GFR was associated with a lower REE. Also, we found reduced REE, but not a fall in GFR, was associated with a fall in dietary protein intake. This supports the hypothesis that patients with CKD have no selective aversion to protein; reduction in dietary protein intake with progressive CKD is due to global reduction in food intake. Conclusions: We conclude that REE falls with declining renal function in patients with CKD. This is likely secondary to combination of reduced energy expenditure of kidneys, adaptation to decreased energy intake or alteration in cellular energy metabolism.

Abstract

O.E. Emovon¹, J.A.C. King², S.R. Smith³, C. Op’t Holt⁴, F. McDonald², D.N. Howell⁵ and B.J. Browne⁴

¹Department of Medicine, ²Department of Pathology, University of South Alabama, Mobile, ³Department of Medicine, Duke University Medical Center, Durham, ⁴Department of Surgery, University of South Alabama, Mobile, Alabama, and ⁵Department of Pathology, Duke University Medical Center, Durham, North Carolina, USA
Aims: Renal allograft biopsies play a critical role in renal transplantation. Acute rejection characterized by tubulitis and intimitis is of primary concern. There is an association between eosinophilic infiltrates and irreversible acute rejection; however, the significance of eosinophils in biopsies that fall short of the diagnostic threshold for acute rejection has not been well studied. This report describes clinical course, treatment and long-term outcome of 5 transplant recipients with biopsy histology that showed borderline changes associated with eosinophilic infiltrates. Methods: Clinical records were selected for review on the basis of biopsy histology satisfying the following criteria: presence of interstitial infiltrates with eosinophils, absence of definitive criteria for acute rejection and absence of findings suggestive of infection or cyclosporine toxicity. Results: All identified biopsies occurred within the first month of transplantation, and histology showed varying degrees of patchy mononuclear cell infiltrates composed of lymphocytes, with eosinophilic infiltrates, but no evidence of acute rejection based on Banff criteria. These patients were taking trimethoprim-sulfamethoxazole and ranitidine at the time of biopsy. Serum creatinine returned to baseline levels in each case after stopping both drugs, and remained stable during the duration of follow-up without any documented episode of acute rejection. No patient received specific therapy for acute rejection. Conclusion: This report suggests that independent of decisions on treatment with high-dose steroids or anti-lymphocyte antibody preparations, the management algorithm should include stopping drugs associated with acute interstitial nephritis when non-diagnostic biopsies show eosinophilic infiltrates.

Abstract

R. Kazancioglu, S. Sahin, R. Has, A. Turkmen, H. Ergin-Karadayi, L. Ibrahimoglu and S. Bozfakioglu

¹Department of Medicine, Division of Nephrology and ²Department of Obstetrics and Gynecology, Istanbul Faculty of Medicine, Istanbul University, and ³Goztepe SSK Hospital, Istanbul, Turkey
Pregnancy among women receiving hemodialysis as a renal replacement therapy is rare and the chance of a successful delivery is relatively low. In this article, we present 3 cases of women conceiving either before or after the initiation of hemodialysis. The various risks of each pregnancy and the outcome are discussed as well as the latest management guidelines for pregnant dialysis patients.

Abstract

N. Ferrara, P. Abete, M. Giordano, P. Ferrara, V. Carnovale, D. Leosco, F. Beneduce, T.Ciarambino, M. Varricchio and F. Rengo

¹Department of Gerontology, Geriatrics and Metabolic Diseases, Second University of Naples, ²“Salvatore Maugeri” Foundation, Telese Terme Institute, IRCCS, and ³Department of Clinical Medicine and Cardiovascular and Immunological Sciences, University of Naples “Federico II”, Italy
Neurotoxicity is an unusual complication of cephalosporin therapy. Only few cases of neurotoxicity induced by Cefepime have been described and probably the frequency of Cefepime-induced status epilepticus is underestimated. We report a case of an 82 year-old male, ESRD patient on chronic hemodialysis program affected by pneumonia, who received a treatment with intravenous Cefepime (1 g/day) and developed a seizure 4 days after the starting antibiotic therapy. Cefepime-induced neurotoxicity was suspected and its administration was immediately discontinued. In order to increase Cefepime clearance a hemodialysis session was urgently started and an improvement of his conscious level was observed. On the following day, after a second hemodialysis session his clinical condition and the status of neurotoxicity were completely recovered. The patient was discharged from the hospital in stable clinical condition one week later. At variance with the cases previously reported, the daily dose of Cefepime administrated to our patient was 50% lower and respected drug prescription dosage. Thus, we speculate on the hypothesis that advanced age of our patient and metabolic encephalopathy induced by chronic uremia made him more sensitive to the neurotoxicity induced by the drug. In conclusion, our case suggests that, in very old patients on long-term hemodialysis, it should be considered, to avoid neurotoxicity, to monitor the clinical neurological status, to use Cefepime at lower dosage than that allowed in patients with severe renal impairment (1 g/day) and, when possible, to evaluate Cefepime plasma levels. However, in these patients, other agents of the same class should be considered such as Cefotaxime and Ceftriaxone which are characterized by both an hepatic and renal excretion. In alternative to cephalosporins, antibiotics with the same action spectrum in the absence of neurological toxicity (i.e. Meropenem) should be recommended.

Abstract

A. Singh and A.T. Webb

Abstract

L.A. Calò, P.A. Davis and A. Semplicini

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Volume 59, No. 5/2003(May)