Volume 61, No. 1/2004(January)
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 Clinical Nephrology
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Originals
Prevalence of proteinuria and the development of chronic kidney disease in HIV-infected patients
Abstract
S.K. Gupta1, B.W. Mamlin2, C.S. Johnson3, M.D. Dollins4, J.M. Topf5 and M.P. Dubé1
1Division of Infectious Diseases, 2Division of General Internal Medicine, 3Division of Biostatistics, 4Division of Nephrology, Indiana University School of Medicine, Indianapolis, IN, and 5Section of Nephrology, The University of Chicago, Chicago, IL, USA
Aims: HIV-related renal diseases are increasingly prevalent and are associated with proteinuria and rapid progression to end-stage renal failure. Early treatment with highly active antiretroviral therapy (HAART) and ACE inhibition may prevent the development of chronic kidney disease (CKD), but studies evaluating the epidemiology of proteinuria and early CKD in HIV-infected patients are lacking. Methods: All consecutive patients at Wishard Memorial Hospital (Indiana University) whose initial HIV documentation occurred from 1990 to 1998, were retrospectively studied using a computerized medical record system. Clinical data were abstracted from time of first HIV documentation through 12/31/2000. The proportions of patients who developed CKD (doubling of serum creatinine from an initial level £ 1.5 mg/dl) and who had proteinuria (³ 1+ protein on the first urine dipstick after HIV documentation) were calculated. Case mix and laboratory variables at the time of HIV documentation were compared between those who did and did not develop CKD and between those who had and did not have initial proteinuria. Results: Of 487 subjects with initially normal renal function, 10 (2% (95% CI, 1 – 4%)) developed CKD. In univariable analysis, black race, a diagnosis of diabetes or hypertension and proteinuria were all significantly associated with the development of CKD; 89 (29% (95% CI, 24 – 35%)) of 289 evaluable subjects had ³ 1+ proteinuria on urine analysis. Multivariable regression revealed only older age (OR 1.08 per year increase; 95% CI, 1.03 – 1.14) to be associated with proteinuria. Conclusions: A small, but potentially clinically meaningful proportion of HIV-infected patients develop CKD, and there appears to be a high prevalence of proteinuria on the first urine analysis obtained after HIV documentation.
Originals
Glomerular expression of biglycan and decorin and urinary levels of decorin in primary glomerular disease
Abstract
M. Kuroda, H. Sasamura, E. Kobayashi, R. Shimizu-Hirota, Y. Nakazato, M. Hayashi and T. Saruta
Department of Internal Medicine, School of Medicine, Keio University, Tokyo, Japan
Aims: Recent studies have suggested that small leucine-rich proteoglycans (SLRP) of the extracellular matrix play a major role in modulating the activity of growth factors and in regulating the deposition of collagens. In this study, the expression of the SLRPs biglycan and decorin in the glomeruli of patients with primary glomerular disease (minimal change disease, IgA nephropathy, and membranous nephropathy) and urine immunoreactive levels were examined. Methods: Renal biopsy specimens were obtained from patients with minimal change disease, IgA nephropathy and membranous nephropathy. Immunohistochemical staining was performed on fresh-frozen samples using anti-biglycan and anti-decorin antibodies. Examination of urine proteoglycan excretion from a total of 26 patients and 8 normal volunteers was performed by indirect ELISA. Results: In normal kidney samples, biglycan and decorin expression was found predominantly in the intrarenal arteries and tubulointerstitium, with only minimal expression in the glomeruli. Glomerular expression of these proteoglycans in glomerular disease was unchanged in all of the 4 patients examined with minimal change disease. In the case of IgA nephropathy or membranous nephropathy, some of the patients showed minimally increased immunostaining of either biglycan or decorin, but there were no signs of simultaneous upregulation of both proteoglycans. To further examine the changes in proteoglycan expression, ELISA was performed on urine samples. Urine biglycan levels were below detection levels, but high values of urine decorin immunoreactivity were found in the patients with glomerular disease. A significant negative correlation was found between urine decorin and creatinine clearance. Conclusion: These results suggest that distinct changes in the expression of the SLRPs biglycan and decorin may be seen in patients with primary glomerular disease. Moreover, the negative relationship between urine decorin levels and renal function supports the hypothesis that decorin may be involved in the pathophysiology of renal dysfunction in humans.
Originals
The remission of nephrotic syndrome with cyclosporin treatment does not attenuate the progression of idiopathic membranous nephropathy
Abstract
D.S. Goumenos, P. Kalliakmani, S. Tsakas, F. Sotsiou and J.G. Vlachojannis
1Department of Internal Medicine-Nephrology, University Hospital, Patras, and 2Department of Pathology, “Evangelismos” General Hospital, Athens, Greece
Background: Idiopathic membranous nephropathy (IMN), a common cause of nephrotic syndrome in adults, is usually treated by combination of corticosteroids with cytotoxic drugs. In cases resistant to this regimen, the use of cyclosporin A (CsA) is followed by frequent remissions of the nephrotic syndrome. Aim: The purpose of this study was to estimate the effectiveness of prednisolone and small doses of CsA as first-line treatment of nephrotic patients with IMN, in relation to the progression of the disease, based on functional and histological changes. Patients and methods: Sixteen patients, with nephrotic syndrome due to IMN and well-preserved renal function, were treated with prednisolone (starting dose: 0.5 mg/kg bw/day) and CsA (starting dose: 3 mg/kg bw/day) for 24 months. A repeat renal biopsy was performed after 18 months of treatment in 10 patients with remission of nephrotic syndrome, to estimate the activity of the disease and to identify any features of CsA toxicity. Results: Remission of the nephrotic syndrome was observed in 14 out of 16 patients after 5 ± 2 months of treatment. Complete remission was observed in 8 and partial remission in 6 patients (urinary protein was reduced from 6.9 ± 3.4 – 0.2 ± 0.06 g/24 h and 1.2 ± 1.0 g/24 h, respectively, p < 0.01). The renal function was well preserved in 13 out of 16 patients over a 24-month period of treatment. Deterioration of renal function was observed in 3 patients (creatinine clearance reduced from 86 ± 21 – 37 ± 17 ml/min, p < 0.05) who had either persistent nephrotic syndrome or frequent relapses. Relapses of the nephrotic syndrome were observed in 5 of 14 patients. Repeat renal biopsies showed that glomerular sclerosis, tubulointerstitial injury, vascular hyalinosis and stage of the disease were deteriorated in most patients. Isometric vacuolization of tubular epithelial cells was observed in 2 of 10 patients. Conclusion: IMN nephrotic patients treated with prednisolone and low doses o f cyclosporin A showed a high remission rate of nephrotic syndrome. However, progression of chronic histological lesions was found in repeat renal biopsies. This suggests that cyclosporin can frequently induce remission of nephrotic syndrome in IMN patients, but even low doses of the drug are not free of potential renal toxicity.
Originals
Mycophenolate mofetil in children with multidrug-resistant nephrotic syndrome
Abstract
A.K. Bayazit, A. Noyan, N. Cengiz and A. Anarat
1Department of Pediatric Nephrology, School of Medicine, Cukurova University, and 2Department of Pediatrics, Adana Hospital, Baskent University, Adana, Turkey
Aim: The aim of the present study is to report our clinical experiences with MMF in problematic children with chronic glomerulonephritis resistant to corticosteroids and/or other immunosuppressive drugs. Patients and methods: Ten patients with chronic glomerulonephritis resistant to treatment with corticosteroids and other immunosuppressive drugs were treated with mycophenolate mofetil (MMF). Causes of chronic glomerulonephritis were mesangial proliferative glomerulonephritis (4), membranoproliferative glomerulonephritis (3), chronic sclerosing glomerulonephritis (1), focal segmental glomerulosclerosis (1), diffuse endo- and extracapillary proliferative glomerulonephritis (1). MMF 15 mg/kg was used in combination with low-dose corticosteroids and angiotensin-converting enzyme inhibitors. Results: During 24 weeks of MMF therapy, no significant changes were detected in mean serum creatinine, albumin and proteinuria. Severe leukopenia was seen in 1 patient. Additional adverse effects, including nausea and diarrhea, were observed in another patient when the dosage was increased to 20 mg/kg per day. During MMF treatment proteinuria decreased slightly without remission in 6 of 10 patients. Conclusion: Further data and clinical trials are needed to evaluate the possible role of MMF in the treatment of chronic glomerulonephritis of similar etiologies in pediatric patients.
Originals
Differential expression of b-chemokines MCP-1 and RANTES and their receptors CCR1, CCR2, CCR5 in acute rejection and chronic allograft nephropathy of human renal allografts
Abstract
M. Rüster1, H. Sperschneider1, R. Fünfstück1, G. Stein1 and H.-J. Gröne2
1Department of Internal Medicine III, Friedrich Schiller University, Jena, and 2Department of Cellular and Molecular Pathology, German Cancer Research Center, Heidelberg, Germany
Background: The b-chemokines MCP-1 (CCL2) and RANTES (CCL5) have been shown to play important roles in acute renal transplant rejection (AR) and chronic allograft nephropathy (CAN). The potential relationship of expression of these chemokines, their chemokine receptors CCR1, CCR2, CCR5, and the cell populations of inflammatory infiltrate, histological and clinical diagnoses were investigated in biopsies at the time of AR and compared with biopsies of CAN. Methods: In 24 renal transplant biopsies with AR (n = 15) and CAN (n = 9), the expression of MCP-1 and RANTES, their receptors CCR1, CCR2, and CCR5 and the infiltration with monocytes/ macrophages and T cells were studied. Results: As previously described, chemokine and chemokine receptor expression was found mainly in mononuclear cells infiltrating the interstitium and glomeruli. In the tubulointerstitial area and glomeruli the expression of MCP-1, RANTES, and their receptors correlated with an infiltration by monocytes/macrophages. Biopsies with CAN revealed a lower expression of MCP-1, RANTES, CCR1, CCR2 and CCR5 in tubulointerstitial cells, and a significantly lower infiltration with MRP14-positive monocytes/ macrophages than biopsies with AR. In AR, MCP-1 and CCR1 showed a lower expression compared to RANTES, CCR2, and CCR5. Conclusions: The positive correlation between chemokines and chemokine receptors and infiltrating leukocytes during acute rejection, the lower but detectable expression of MCP-1, RANTES, CCR1, CCR2 and CCR5 in CAN, and the differences in the quantity of expression between the different chemokines and chemokine receptors point to a complex regulation of chemokine expression in renal allografts. Since chemokines are not only involved in inflammation but also in tissue regeneration, this could have impact on the development of CAN.
Originals
Single and serial measurements of cardiac troponin I in asymptomatic patients on chronic hemodialysis
Abstract
M.A. Roberts, D. Fernando, N. Macmillan, G. Proimos, L.A. Bach, D.A. Power, S. Ratnaike and F.L. Ierino
1Department of Nephrology, 2Department of Cardiology, 3Division of Laboratory Medicine, and 4Department of Medicine, Austin Health, Heidelberg, Victoria, Australia
Aims: Coronary artery disease is the major cause of death in patients with end-stage renal failure on dialysis. This study aimed to assess the predictive value of a single cardiac troponin I (cTnI), and also the kinetics of serial values. Methods: Since cTnI is a potential biomarker of cardiac outcome, the present study examined single cTnI measurements (n = 88 patients) and its predictive value for future cardiac events, and a kinetic substudy of serial weekly cTnI measured for 8 weeks (n = 57) in a group of patients on hemodialysis. Results: Single cTnI measurements: 9 patients (10.2%) had a detectable cTnI at baseline and 79 patients (89.8%) had a negative baseline cTnI. There were no significant differences in age, sex, history of ischemic heart disease, diabetes, smoking or dyslipidemia between patients with detectable and negative cTnI. At the end of 9 months, the rate of combined primary endpoints, which included myocardial infarction, cardiac death and cardiac revascularization, was significantly higher in the patients with a detectable baseline cTnI (55.6%), compared to patients with a negative cTnI (6.3%) (p = 0.0007). Serial weekly cTnI measurements: significant fluctuations in cTnI were noted over time; 27% of patients with an undetectable cTnI measured at baseline had subsequent detectable levels in the serial follow-up. Conclusion: A single detectable cTnI in asymptomatic patients on hemodialysis defines patients at high risk of future cardiac events. However, the incidence of detectable cTnI levels is markedly increased when serial weekly measurements are performed. The clinical significance of detectable serial measurements of cTnI is the focus of ongoing studies.
Originals
Efficacy of reteplase in poorly functioning hemodialysis catheters
Abstract
A. Falk, W. Samson, J. Uribarri and J.A. Vassalotti
1Department of Radiology, and 2Department of Medicine, Division of Nephrology, The Mount Sinai-NYU Medical Center, New York, NY, USA
Aim: This is a retrospective study of reteplase efficacy for restoration of flow in occluded and poorly functioning hemodialysis catheters. Patients and methods: From May 1, 2001 to December 31, 2001, all hemodialysis patients seen at our university dialysis center with occluded or poorly functioning (< 200 ml/min blood flow) catheters treated with reteplase were included in the study. All catheters had been in place for more than 48 hours. Reteplase 0.4 U was instilled into each port; dwell time was 30 minutes. If aspiration had not been possible, reteplase had remained in the catheter for an additional 30 minutes. If flow was established (> 200 ml/min), the catheter was used for dialysis. If flow was not adequately established after 1 hour, the patient was referred for catheter exchange. Results: Reteplase (0.4 U) was used in 50 instances to restore or improve blood flow rates in a total of 23 catheters in 19 patients. Reteplase was effective in establishing adequate blood flow rates during the current and next dialysis session in 44/50 (88%) cases; 6 cases required 1-hour dwell time. Six cases (in 5 patients) required catheter exchange; in these, an anatomic or pathologic complication was responsible for catheter malfunction. No adverse events were related to reteplase instillation during the study. Conclusion: Data suggest that reteplase is safe and effective in restoring flow to malfunctioning hemodialysis catheters. Results are comparable to those achieved with alteplase.
Originals
Hyponatremia in peritoneal dialysis patients
Abstract
J. Uribarri, S. Prabhakar and T. Kahn
1Renal Division, Mount Sinai School of Medicine, New York, USA and
2Renal Division, Texas Tech University Health Sciences Center, Lubbock, Texas (SP) and 3Bronx Veterans Administration Medical Center, Bronx, New York, USA
Background: Low serum sodium is uncommon in peritoneal dialysis (PD), which is surprising in view of the important role of normal kidney function to regulate water and sodium balance. Methods: We report 2 cases of persistent hyponatremia with balance studies in Case 1. We performed measurements of dialysate sodium and volume output over 24 hours in a group of chronic PD patients. Results: The low serum sodium concentration did not vary too much with overall fluid removal via dialysis in patient 1, mainly because large quantities of sodium were removed in the dialysate. In the 24-hour studies, a significant relationship was found between net daily PD sodium removal and net daily dialysate volume removed (r = 0.65). There was no relationship between net daily PD sodium removal and serum sodium concentration. There was a linear direct correlation between serum and dialysate sodium concentration (r = 0.8) as shown by others previously. Conclusions: These results suggest that the main determinant of PD sodium loss is net dialysate ultrafiltration volume. Water loss via dialysis is necessarily associated with sodium loss. In order to maintain a normal serum sodium concentration salt intake must be proportional to the water loss induced by dialysis. The stimuli that allow dialysis patients to maintain this delicate balance between water and salt intake are of considerable interest but remain undetermined.
Case reports
Pregnancy in membranous glomerulonephritis – course, treatment and outcome
Abstract
Z. Katzir, S. Rotmensch, M. Boaz, A. Biro, A. Michlin and S. Smetana
1Nephrology and Hypertension Institute, 2Department of Gynecology and Obstetrics, and 3Epidemiology Unit, the E. Wolfson Medical Center, Holon, Israel
Background: The effect and outcome of pregnancy in women with preexisting glomerulonephritis is a controversial issue. Case: We report the clinical course and treatment of a 23-year-old pregnant woman with biopsy-proven membranous glomerulonephritis. When she conceived, the patient had been in stable remission for 1 year. In the 14th week of pregnancy, the patient developed uncontrolled hypertension and nephrotic syndrome. Daily 1 g methylprednisolone intravenous pulses were administered for 3 days, followed by a 4-week course of oral prednisone, 50 mg/day. Clinical improvement and normalization of arterial blood pressure were achieved. Oral prednisone 60 mg was administered on alternate days for another 4 weeks following 3 days of pulse therapy. At the end of treatment (26th gestational week), we observed a decrease of proteinuria (from 10.6 – 4.8 g/24 h) and rise in serum albumin (from 2.1 – 2.9 g/100 ml). At this time, blood pressure was 130/85. In the 34th week, a normal healthy male newborn was delivered by cesarean section. One year later she felt well, her blood pressure was 140/90, serum albumin was 3.4 g/100 ml, urine protein was 1.65 g/24 h and renal function was normal. The patient’s child was healthy and well developed. Conclusion: Judicious use of a specific therapy to the underlying renal disease during pregnancy, together with a continuous supervision, can improve outcomes of these particular high-risk conditions.
Case reports
Pamidronate-induced nephrotoxic tubular necrosis – a case report
Abstract
S. Smetana, A. Michlin, E. Rosenman, A. Biro, M. Boaz and Z. Katzir
1Nephrology Institute and 4Epidemiology Unit, Edith Wolfson Medical Center, Holon, 2Sackler Faculty of Medicine, Tel Aviv University, and
3Pathology Institute, Shaare Zedek Medical Center, Jerusalem, Israel
Few cases of pamidronate (bisphosphonate class of drugs) nephrotoxicity in humans have been previously reported in the literature. In 7 patients, the pamidronate-related nephrotoxicity was attributed to focal collapsing glomerulosclerosis [Markowitz et al. 2001], and in 1 patient was related to tubulo-interstitial inflammatory nephritis [Van Doorn et al. 2001]. We report herein on a 65-year-old Caucasian female patient who presented with acute chronic renal failure due to pamidronate-induced toxic proximal tubular necrosis without immunologic or inflammatory tubulo-interstitial involvement. The acute pattern of renal failure resolved following cessation of pamidronate administration in this patient for osteoporosis; the patient also had a monoclonal gammopathy of unspecific origin (MGUS).
Case reports
A case of secondary hyperparathyroidism whose high turnover bone improved after the direct injection of acetic acid into the parathyroid glands
Abstract
N. Onoda, S. Kurihara, Y. Sakurai, E. Osono, K. Owada, M. Suga, H. Adachi and H. Yoneshima
Division of Nephrology, Kasukabe Shuwa Hospital, Saitama, Japan
A 48-year-old male was admitted to our hospital because of increasing knee pain and thigh muscle weakness. He had been undergoing hemodialysis for 15 years. His serum intact PTH value was 1,600 pg/ml with elevated ALP (387 IU/l) and osteocalcin (400 ng/ml). Ultrasound (US) examination disclosed 2 enlarged parathyroid glands. Because of poor cardiac function, an US-guided acetic acid injection into the enlarged parathyroids (percutaneous acetic acid injection therapy; PAIT) was performed. Soon after the PAIT, his arthralgia disappeared. Serum PTH fell to 220 pg/ml with the regression of bone marker 1 year following the PAIT. The size of his parathyroid glands dramatically regressed and 1 of the enlarged glands finally disappeared. Repeated bone biopsies following double tetracycline labeling showed a significant improvement from osteitis fibrosa to the mild lesion. This is the first known case report of severe secondary hyperparathyroidism whose PTH and high turnover bone was successfully managed by the direct injection of acetic acid into the parathyroid glands. As long as we pay attention to avoiding recurrent nerve palsy induced by acetic acid, US-guided PAIT may be an alternative to percutaneous ethanol injection therapy (PEIT) or surgical parathyroidectomy (PTx).
Case reports
Mechanical hemolysis in a hemodialysis patient with carotid-jugular arteriovenous fistula
Abstract
K.-L. Kuo, Y.-H. Chou and D.-C. Tarng
1Division of Nephrology, Department of Medicine, 2Department of Radiology, Taipei Veterans General Hospital, and 3Faculty of Medicine, National Yang-Ming University School of Medicine, Taipei, Taiwan
Renal anemia is mainly caused by inadequate synthesis of erythropoietin from diseased kidneys. At the present time, recombinant human erythropoietin (rHuEPO) is used to correct anemia successfully in most patients with end-stage renal diseases. Nevertheless, poor response to rHuEPO still exists in some hemodialysis patients and its mechanism in some cases remains obscure. Herein, we describe a rare case of rHuEPO hyporesponsiveness due to mechanical hemolysis induced by a traumatic carotid-jugular arteriovenous fistula (AVF) in the presence of subclinical aluminum intoxication. Following surgical resection of the traumatic AVF and 8 months of desferrioxamine treatment, the responsiveness to rHuEPO was restored and the rHuEPO dose requirements reduced.
Letters to the Editor
Acute renal failure secondary to hemoglobinuria in a patient with a left ventricular assist device
Abstract
R.P. Varghese, B. Piraino and M. Unruh
Letters to the Editor
Recurrence of type III membranoproliferative glomerulonephritis after renal transplantation
Abstract
G.V. Ramesh Prasad, F. Shamy and J.S. Zaltzman
Letters to the Editor
An unusual case of a vesical stone presenting gross hematuria in a boy
Abstract
H.J. Kim, Y.B. Jeong, S. Lee, W. Kim and S.K. Park
