Volume 60, No. 2/2003(August)
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 Clinical Nephrology
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Originals
The pathogenesis of membranoproliferative glomerulonephritis in KwaZulu-Natal, South Africa is unrelated to hepatitis C virus infection
Abstract
N.D. Madala, S. Naicker, B, Singh, M. Naidoo, A.N. Smith and K. Rughubar
1Department of Medicine, 2 Department of Virology, and 3 Department of Anatomical Pathology, Nelson R. Mandela School of Medicine, University of Natal, Durban, South Africa
Idiopathic membranoproliferative glomerulonephritis (MPGN) is a well-defined clinicopathological entity with a poor prognosis, with 50% of patients progressing to end stage renal disease (ESRD) within 10 years. It was reported in about 36% of adult Black patients with nephrotic syndrome in our center previously [Seedat et al. 1988]. Hepatitis C virus (HCV) infection has been shown to be associated with cryoglobulinemic as well as non-cryoglobulinemic (or idiopathic glomerulonephritis). The aim of this study was to determine whether an association exists between HCV infection and idiopathic MPGN in a population with a relatively high prevalence of MPGN. We studied adult patients referred with glomerular disease over a two-year period, 104 patients had primary glomerulonephritis. All 23 (22%) patients with idiopathic MPGN were enrolled, as well as 32 age-matched patients presenting with other primary glomerular diseases. We examined serum from all 55 patients for evidence of HCV antibodies and HCV RNA. None of the 55 patients showed evidence of HCV infection. Chronic renal failure was present in 82.6% of the patients with idiopathic MPGN and it was advanced in 52,2%, who either were dialysis-requiring at presentation or progressed to ESRD soon thereafter; 30.4% had moderate chronic renal failure, while only 17.4% had normal renal function. HCV infection is not associated with idiopathic MPGN in our patients. Idiopathic MPGN remains an idiopathic disease, possibly with a poor prognosis in our population.
Originals
Clustering of post-diarrheal (Shiga toxin-mediated) hemolytic uremic syndrome in families
Abstract
R.L. Siegler, J.R. Sherbotie, N.D. Denkers and A.T. Pavia
1Division of Nephrology and Hypertension, and
2Division of Infectious Diseases, Department of Pediatrics,
University of Utah School of Medicine, Salt Lake City, USA
Aims: 1. To study the epidemiological and clinical features of Shiga toxin (Stx)-mediated (post-diarrheal) hemolytic uremic syndrome (HUS) occurring in more than 1 family member. 2. To compare familial with non-familial episodes, and concurrent familial with non-concurrent familial cases. 3. To determine the likelihood of Stx HUS occurring in a second family member. Methods: A retrospective review from January 1970 through September 2001 of families in whom Stx HUS occurred in more than 1 family member was conducted using a computerized HUS registry. It contains information on 373 episodes that occurred in 356 families from Utah and neighboring states. Cases were categorized as being either concurrent (i.e., occurring within a month of one another) or non-concurrent, and the study was limited to those with typical (post-diarrheal) episodes. Results: HUS occurred in 2 or more family members in 17 (4.8%) of the families in our registry. In 12 (3.4%) of these families episodes occurred with days to weeks of each other; in 5 families (1.4%) episodes were separated by intervals of several years. There were no statistically significant differences in demographic, seasonal, laboratory, clinical, or outcome variables between familial subsets (concurrent versus non-concurrent) or between familial and non-familial cases. Conclusions: When a child is diagnosed with D+ HUS, there is an increased risk that a second family member will also develop HUS; most often within days to weeks (i.e., within a month), but in some cases episodes may be separated by intervals of years. Non-concurrent cases suggest common environmental risk factors, or perhaps a genetic predisposition. Concurrent cases suggest a common source of infection or person-to-person transmission; a genetic predisposition cannot be excluded. These observations suggest that siblings of an index case who develop diarrhea should be kept under close surveillance.
Originals
Outcome of Henoch-Schoenlein nephritis with nephrotic-range proteinuria
Abstract
J. Ronkainen1, M. Ala-Houhala2, N.-P. Huttunen3, T.Jahnukainen4, O. Koskimies5, T. Örmälä6 and M. Nuutinen1
1Department of Pediatrics, Oulu University Hospital, Oulu,
2Department of Pediatrics, Tampere University Hospital, Tampere,
3Department of Pediatrics, Jyväskylä Central Hospital, Jyväskylä,
4Department of Pediatrics, Turku University Hospital, Turku,
5Department of Pediatrics, Helsinki University Central Hospital, Helsinki, and 6Department of Pediatrics, Kuopio University Hospital, Kuopio, Finland
Patients and methods: All children with Henoch-Schoenlein glomerulonephritis (HSP-GN) and nephrotic-range proteinuria (> 40 mg/h/m2), treated at 5 university hospitals and in 1 central hospital in Finland during in 1990 ? 1997, were analyzed retrospectively. The mean age of these 19 patients (8 girls, 11 boys) at the time of diagnosis was 9.9 years (range 4.6 ? 15.1 years). A renal biopsy had been performed in all cases, giving findings according to the classification used in the International Study of Kidney Diseases in Children (ISKDC) of grade II (4 patients), grade III (10), grade IV (4) and grade V (1). Six patients underwent a second biopsy. Results: The yearly incidence of nephrotic-range HSP-GN in Finland was 2 per 1 million children under 15 years of age. After a mean follow-up of 4.6 years (range 9 months ? 9.1 years), 3 patients (15.7%) had no signs of nephritis, 11 (57.9%) had proteinuria < 1 g/day or microscopic hematuria, 2 (10.5%) had proteinuria > 1 g/day, and 3 (15.7%) had developed ESRD or uremia. 47% of the patients needed medication for proteinuria at the time of the latest follow-up. The first kidney biopsy did not predict the outcome of HSP-GN, since all the patients with the poorest outcome had only ISKDC II-III findings in their first biopsy. Conclusion: According to our series, the morbidity in cases of HSP-GN with nephrotic-range proteinuria is high and a close clinical follow-up is needed. The treatment of HSP-GN patients should be based on the clinical presentation rather than on the biopsy findings.
Originals
Effect of fluvastatin and dipyridamole on proteinuria and renal function in childhood IgA nephropathy with mild histological findings and moderate proteinuria
Abstract
K. Kano, K. Nishikura, Y. Yamada and O. Arisaka
Department of Pediatrics, Dokkyo University School of Medicine, Tochigi, Japan
Aim: In recent reports, some kinds of HMG-CoA reductase inhibitors were able to decrease proteinuria and to improve renal function. Here we aimed to clarify the effect of fluvastatin (an HMG-CoA reductase inhibitor) on proteinuria and renal function in children with mild IgA nephropathy. Patients and methods: We conducted a prospective controlled study of 30 children who had been recently diagnosed with normocholesterolemic IgA nephropathy following the detection of a minor lesion or of focal mesangial proliferation and moderate proteinuria. The 30 patients were randomly assigned to receive both of 20 mg of fluvastatin and 5 mg/kg of dipyridamole (group 1), or 5 mg/kg of dipyridamole only (group 2) for 1 year. Results: By the end of the trial, urinary protein, hematuria, BUN and serum creatinine levels had significantly decreased in the patients of group 1 as compared to baseline. Serum total cholesterol, triglyceride and LDL cholesterol levels had significantly decreased, while serum total protein and albumin, and creatinine clearance had significantly increased in group 1 as compared to baseline and group 2. The urinary protein level had significantly decreased in the group 2 patients as compared to baseline, but only slightly. Conclusions: The results of this study suggest that fluvastatin and dipyridamole treatment yields an antiproteinuric effect and leads to the amelioration of renal function in moderately proteinuric patients with mild histological IgA nephropathy.
Originals
Pharmacokinetics of nateglinide and its metabolites in subjects with type 2 diabetes mellitus and renal failure
Abstract
T. Inoue, N. Shibahara, K. Miyagawa, R. Itahana, M. Izumi, T. Nakanishi and Y. Takamitsu
1Blood Purification Center, Osaka Medical College, Osaka, and
2Department of Kidney and Dialysis, Hyogo College of Medicine, Hyogo, Japan
Aims: We evaluated the benefits and safety of nateglinide, a novel oral hypoglycemic agent, in type 2 diabetes patients with renal failure. Methods: Single-dose pharmacokinetics were studied in 8 patients with type 2 diabetes and a low creatinine clearance (range 1.8 ? 16.5 ml/min/1.73 m2) up to 6 hours after 90 mg nateglinide administration. Next, we treated another group of 8 patients undergoing regular hemodialysis with nateglinide 90 mg/day for 1 ? 3 months. The effect of hemodialysis on metabolite accumulation was then tested. Results: After a single 90 mg dose, nateglinide significantly increased the post-prandial secretion of insulin and thereby reduced plasma glucose levels. Mean pharmacokinetic parameters (AUC0-6 10.45 mg/l/h; t1/2 1.89 h, Cl/F 10.19 l/h) were comparable with those reported in healthy subjects. A much larger AUC value than those previously reported of M1, a major metabolite in the urine of healthy subjects, was observed, and the plasma concentration of M1 did not decline up to 6 hours after. In patients treated on a regular basis, there was marked accumulation of M1, while nateglinide could not be detected 24 hours after the last dose. Plasma M1 levels were significantly reduced by the hemodialysis sessions. Conclusions: Single 90 mg dose of nateglinide was safe and effective in patients with renal failure. However, repeated administrations could cause prolonged hypoglycemia due to accumulation of M1, which is known to have a modest hypoglycemic activity. Hemodialysis may help to eliminate excessive accumulation of M1.
Originals
Comparison of 3 vancomycin dosage regimens during hemodialysis with cellulose triacetate dialyzers: post-dialysis versus intradialytic administration
Abstract
N.A. Mason, B.L. Neudeck, L.S. Welage, J.A. Patel and R.D. Swartz
1College of Pharmacy, The University of Michigan, 2Department of Pharmacy Services, University of Michigan Health System, 3School of Pharmacy, University of Wisconsin, 4Clinical Pathology Laboratories, University of Michigan Health System, and 5Division o
Aims: Traditionally, vancomycin is administered following dialysis to minimize drug loss when high-flux membranes are employed. Unfortunately, this approach is extremely inconvenient for patients and staff, requiring the patients to remain in the unit for at least 1 hour following dialysis. This study was designed to evaluate the feasibility of administering vancomycin during hemodialysis. Specifically, this study was designed to compare the pharmacokinetics of vancomycin when administered during the last 1 ? 2 hours of dialysis (i.e. intra-dialytic administration) to that administered after completion of dialysis. Materials and methods: In a randomized, 3-way crossover trial, the pharmacokinetics of vancomycin were evaluated in 9 hemodialysis patients, comparing vancomycin 15 mg/kg following dialysis (Phase I), vancomycin 15 mg/kg during the last hour of hemodialysis (Phase II) or vancomycin 30 mg/kg during the last 2 hours of hemodialysis (Phase III). Vancomycin plasma concentrations were obtained over an 8-day period and subsequent comparisons between the treatment approaches were made with paired t-tests or ANOVA, as appropriate. Dialysate vancomycin concentrations determined on Day 1 and Day 3 of Phases II and III were used to calculate the fraction of vancomycin dose removed, and were compared to plasma data using paired t-tests. Results: Vancomycin was significantly removed (33.4 to 39.5%) during a 3- to 4-hour high-flux dialysis session occurring on Day 3 after vancomycin administration. Mean serum concentrations immediately following intradialytic vancomycin administration of 15 mg/kg over the last hour of dialysis or 30 mg/kg over the last 2 hours of dialysis were initially high (77.7 and 95.5 mcg/ml respectively), but fell to 25.9 and 40.5 mcg/ml, respectively, by 4 hours post-dialysis. Predialysis concentrations on Days 3, 5 and 8 were similar for vancomycin 30 mg/kg administered over the last 2 hours of dialysis as compared with a 15 mg/kg dose given after dialysis. Vancomycin 15 mg/kg over the last hour of dialysis resulted in significantly lower subsequent predialysis concentrations than the other dosing schemes. Conclusions: Vancomycin administration of 30 mg/kg over the last 2 hours of dialysis achieves serum concentrations similar to conventional dosing of 15 mg/kg after dialysis and would allow dosing on a weekly basis.
Originals
Biofeedback controlled hemodialysis (BF-HD) reduces symptoms and increases both hemodynamic tolerability and dialysis adequacy in non-hypotension prone stable patients
Abstract
C.W. McIntyre, S.H. Lambie and R.J. Fluck
Department of Renal Medicine, Derby City General Hospital, Derby, UK
Background: It is now possible to link relative blood volume (RBV) measurements to a software loop designed to actuate a biofeedback response. This allows changes in RBV to determine constant alterations in both ultrafiltration rate and dialysate conductivity. RBV, plasma sodium and weight loss are driven throughout the treatment to achieve the best compromise. This system has been demonstrated to markedly reduce intradialytic hypotension in unstable patients. We have applied this treatment to stable, non-hypotension prone HD patients and report on the short-term outcomes. Methods: We prospectively studied all 15 patients in a dedicated 4-station minimal care treatment area. Patients were studied for 3 weeks of standard HD, to understand the morphology and response to RBV in that individual. BF-HD was then instituted for a similar period (after a 2-week optimization period). Dialysis adequacy was assessed with equilibrated Kt/V measurements and urea mass removed in spent dialysate. Results: We studied 263 treatment sessions. There was a reduction in symptomatic episodes (per patient over 3 weeks) from 3 ± 0.5 (0 – 9) to 0.13 ± 0.13 (0 – 2) with BF-HD, p < 0.001. Reductions in systolic BP > 40% fell from 1.4 ± 0.4 (0 – 4) to 0.46 ± 0.16 (0 – 2). Episodes of RBV falling > 10% fell from 6.3 ± 0.85 (1 – 13) to 1.13 ± 0.27 (0 – 4) with BF-HD, p < 0.001. Interdialytic weight gains fell from 2.08 ± 0.05 (0.35 – 3.8) kg to 1.82 ± 0.06 (0 – 3.7) kg, p = 0.009. Equilibrated Kt/V increased from 1.01 ± 0.03 (0.61 – 1.35) to 1.13 ± 0.03 (0.7 – 1.5), p = 0.01, and mass removed of urea increased from 24.9 ± 3 (12.8 – 45) g to 32.7 ± 1.9 (17.3 – 48.5) g. Conclusions: This is the first report of BF-HD increasing tolerability, reducing interdialytic fluid gains and enhancing urea clearance in non-hypotension prone chronic HD patients. These data suggest that the previously reported associated benefits of BF-HD may be applicable to the majority of HD patients.
Originals
Tuberculous peritonitis in uremic patients
Abstract
K.-H. Hung, C.-T. Lee, J.-B. Chen and K.-T. Hsu
Division of Nephrology, Department of Internal Medicine, Chang Gung Memorial Hospital at Kaohsiung, Taiwan, R.O.C.
Aims: To identify clinical features and treatment response of tuberculous peritonitis (TBP) in a uremic population, a retrospective case-control study was performed. Materials and methods: Thirteen uremic patients with TBP (Group I: 62.7 ± 6.8 years, male 54%) collected between January 1986 and January 2002 were compared with another two age- and sex-matched controls: 19 non-azotemic patients with TBP (Group II: 62.9 ± 7.3 years, male 47%) and 30 uremic patients without TBP (Group III: 61.1 ± 8.7 years, male 47%). Clinical information and data of ascites and blood examinations were evaluated. Results: Significant differences between Groups I and II were found in comorbidity, hypertension, anorexia, percentages of neutrophil and lymphocyte from blood and ascites, and serum calcium (sCa), phosphorus and albumin-adjusted calcium (sAACa). However, no significant differences in duration of symptoms, coexistent pulmonary tuberculosis (p = 0.061), duration or complications of therapy and mortality (p = 0.13) were detected. Significant differences between Groups I and III were found in peripheral white cell counts and percentages of neutrophil and lymphocyte as well as in serum creatinine (sCr), albumin, sCa, sAACa and intact parathyroid hormone (iPTH). Conclusions: Non-specific symptoms make the diagnosis of TBP in a uremic population difficult. However, neutrophil predominance in blood and ascites, hypoalbuminemia, relatively lower sCr and hypercalcemia with suppressed serum iPTH were found to be characteristic. In TBP uremic patients, therapy complications were not common and there was a tendency for higher mortality, largely due to septic shock.
Case reports
Four cases of red blood cell aplasia in association with the use of mycophenolate mofetil in renal transplant patients
Abstract
W. Engelen, G.A. Verpooten, M. Van der Planken, M.F. Helbert, J.L. Bosmans and M.E. De Broe
Department of Nephrology, University Hospital, Antwerp, Belgium
Mycophenolate mofetil (MMF) is one of the new immunosuppressive drugs used in renal transplantation. MMF inhibits the de novo purine synthesis. Since this purine synthesis in lymphocytes entirely depends on the de novo pathway, MMF is considered to cause a selective inhibition of T-and B lymphocytes. Recently, 4 transplant patients out of 30 developed a severe anemia in the early post-transplantation period. Their immediate post-transplantation immunosuppression consisted of corticosteroids, cyclosporine and MMF. They all received anti-T-lymphocyte globulin (ATG) as induction treatment or because of rejection. In all 4 patients, iron supplementation and a treatment with erythropoietin were started. Blood loss, deficiencies, hemolysis, drug interactions or viral infections were excluded as causes of the anemia. Bone marrow biopsies were carried out, showing pure red cell aplasia that was ascribed to the use of MMF. Cessation or reduction of MMF was followed by a hematological improvement after 5 ? 9 days. We hypothesized that MMF has a broader antiproliferative effect than its proposed lymphocyte-specific effect.
Case reports
Infection with polyomavirus type BK after renal trans-plantation
Abstract
M. Schmitz, M. Brause, G. Hetzel, U. Helmchen and B. Grabensee
1Clinic for Nephrology and Rheumatology, Heinrich Heine University, Düsseldorf, and 2Institute for Pathology, University Hospital Eppendorf, Hamburg
Tubulointerstitial nephritis caused by polyomavirus of the subtype BK (BK virus nephropathy, BKN) is an important cause of deterioration of renal allograft function after kidney transplantation. In 3 cases of BKN diagnosed at our center, the suspected diagnosis made on the basis of urine cytology and serum PCR was confirmed by electron microscopy and immunohistology of the renal graft biopsy. In 1 patient, stable renal function without further virus detection was seen after reduction of the immunosuppression. In 2 further patients there was loss of graft function. BKN is an important differential diagnosis of unclear deterioration of renal graft function. The risk is particularly high with use of tacrolimus and mycophenolate mofetil (MMF). Urine cytology and serum PCR are suitable screening tests, histology provides conclusive evidence. The only therapeutic option available at present is reduction of immunosuppressive therapy.
Case reports
Acute aortic thrombosis and renal infarction in acute cocaine intoxication: a case report and review of literature
Abstract
Y. Mochizuki, M. Zhang, L. Golestaneh, S. Thananart and M. Coco
Montefiore Medical Center, Albert Einstein College of Medicine, Bronx, New York, USA
Emergency room visits related to cocaine use have been increasing over the past 10 years, with the cost of cocaine-related hospitalization now more than 80 million dollars per year. Well-recognized and common complications associated with cocaine use include hypertension, cardiac ischemia, cerebrovascular accidents and rhabdomyolysis. Renal infarction is uncommon, while aortic involvement is even less documented in literature. We present the first report of a case of renal infarction and aortic thrombus in a patient who used nasal cocaine. This case suggests that aortic pathology should be considered in patients presenting with renal infarction related to cocaine use.
Case reports
Primary amyloidosis with multiple pulmonary nodular lesions and IgA nephropathy-like renal involvement
Abstract
M.L. Onozato, A. Tojo, S. Ogura, K. Asaba, A. Goto and T. Fujita
Division of Nephrology and Endocrinology, University of Tokyo, Japan
A 66-year-old woman demonstrated multiple nodular lesions in the lungs without symptoms, and laboratory tests and transbronchial lung biopsy (TBLB) had been negative for malignancy, tuberculosis and sarcoidosis 15 years ago. She developed proteinuria and hematuria 10 years later. Renal biopsy revealed focal segmental mesangial proliferation with predominant IgA deposition in the paramesangium, suggesting IgA nephropathy. However, electron-microscopic observation revealed 8 ? 12 nm fibril deposits in the interstitium and few in the mesangium that were positively stained with amyloid P protein and negative for amyloid A protein. Re-evaluation of previous TBLB samples showed apple-green birefringence with Congo-red staining that was resistant to potassium permanganate reaction. Electron-microscopic observation with high magnification and immunostaining for amyloid components led to a diagnosis of AL amyloidosis in this patient with predominant mesangial IgA deposition and slowly progressive nodular lesions in the lungs.
Case reports
Positron emission tomography reveals a leiomyosarcoma causing proteinuria
Abstract
B. Hegner, B. Krakamp, J.-P. Hedde, M. Brockmann, M. Weber and E. Schulze-Lohoff
1Department of Medicine I, 2Institute of Radiology, and 3Institute of Pathology, Merheim Medical Center, Cologne General Hospital, Medical Faculty of Cologne University, Cologne, Germany
Obstruction of the renal veins may result in proteinuria and is frequently caused by thrombosis or tumorous processes. Since thrombosis and malignancy may occur simultaneously in the venous outflow of the kidneys, search for an underlying intraluminal tumor may be impeded by extensive thrombosis in the lumen of renal and caval veins. We report the case of a 30-year-old man with moderate proteinuria which was caused by an obstructing process of the vena cava inferior and the renal veins. While the obstructive mass was initially misdiagnosed as thrombosis, positron emission tomography helped to reveal the tumorous character of the lesion and fine-needle biopsy allowed rapid diagnosis of a leiomyosarcoma originating from the caval or renal veins. We conclude that undelayed diagnosis of the cause of renal and caval vein obstruction is facilitated by early positron emission tomography and subsequent fine-needle biopsy to identify possible tumorous lesions.
Case reports
Acute renal failure from complete uterine prolapse: role of polycystic kidney disease
Abstract
J.L. Alexander, R. Rustom and J.M. Bone
Department of Medicine, University of Liverpool, Liverpool, UK
A 48-year-old female developed acute renal failure from obstruction caused by a complete uterine prolapse. She had polycystic kidney disease (ADPKD) with previously stable mild renal impairment. She presented with rapidly declining renal function and oliguria which reversed following manual reduction of the prolapse and insertion of a ring pessary. None of the usual risk factors for uterine prolapse were present, however ADPKD may have contributed to the prolapse. Rapid deterioration of renal function in female patients with ADPKD should prompt gynecological examination to exclude a uterine prolapse as a cause.
Letters to the Editor
Mesangiocapillary glomerulonephritis associated with ulcerative colitis: a 6-year follow-up of 2 cases
Abstract
N. Ashman, M. Sheaff and M.J. Raftery
Letters to the Editor
Effect of sivelestat, an inhibitor of neutrophil elastase, on rapidly progressive glomerulonephritis
Abstract
J. Soma, K. Sato, M. Suzuki, Y. Segawa and Y. Miyate
