Role of ticlopidine on adriamycin-induced nephropathy.

The effect of ticlopidine on rats with adriamycin nephropathy was observed during 26 weeks. In the ticlopidine-treated nephrotic animals (TNG), proteinuria was less than in the untreated nephrotic animals (NG), but this difference was significant only at week 6 (TNG = 47.27 +/- 16.52 versus NG = 100.08 +/- 13.83 mg/24 h, p < 0.01) and week 26 (TNG = 157.00 +/- 28.73 versus NG = 217.00 +/- 21.73 mg/24 h, p < 0.01) after ADR injection. NG presented severe tubulointerstitial abnormalities with a tubulointerstitial lesion index of 3+. No difference in glomerular lesions was observed among the groups (NG median = 6%, TNG median = 4% and TCG median = 2%). The tubulointerstitial lesion index of TNG was less intense (median = 2+) but not different from those of the control groups (CG median = 1+; TCG median = 0+) nor NG (median = 3+). We concluded that the treatment with ticlopidine produced some partially beneficial effects but did not prevent the development of adriamycin-induced nephropathy.     

Effect of allopurinol in the course of adriamycin induced nephropathy

The role of superoxide in adriamycin-induced nephropathy (single dose; i.v. 3 mg/kg) has been studied by blocking superoxide synthesis through the administration of allopurinol (500 mg/L in drinking water). In Experiment I (EI), allopurinol administration was started 3 days prior to nephropathy induction and continued until day 14. In Experiment II (EII) allopurinol administration was started 2 weeks after nephropathy induction and was maintained until the end of the experiment (26 weeks). Affected glomeruli frequency and tubulointerstitial lesion index (TILI) were determined at Weeks 2 and 4 (EI) and Week 26 (EII). In EI, the 24 h mean proteinuria in the nephrotic control group (NCG-I) differed from that of the treated nephrotic group (TNG-I) at Week 1 (TNG = 33.3 +/- 6.39 mg/24 h; NCG = 59.8 +/- 6.3 mg/24 h; p < 0.05) and 2 (NCG-I = 80.0 +/- 17.5 mg/24 h; TNG-I = 49.1 +/- 8.4 mg/24 h; p < 0.05). No glomerular alterations were observed and TILI medians were not different in both nephrotic groups at week 2 (NCG-I = 1+: TNG = 1+) and 4 (NCG = 4+; TNG = 4+). In EII, NCG-II and TNG-II presented different 24 h proteinuria values only at Week 6, (136.91 +/- 22.23 mg/24 h and 72.66 +/- 10.72 mg/24 h, respectively; p < 0.05). Between nephrotic groups, there was no statistical difference in the median of affected glomeruli (CNG-II = 56%; TNG-II = 48%) and TILI (NCG-II = 8+; TNG-II = 9+). Thus, allopurinol was associated with a transient reduction in proteinuria and it did not alter the progression of the nephropathy.     

Elevated Plasma Fibronectin Levels in Rats with Immune and Toxic Glomerular Diseases

We measured plasma fibronectin levels by a rocket immunoelectrophoresis in rats with chronic serum sickness induced by repeated injections of ovalbumin and in rats with epithelial nephropathy induced by a single injection of adriamycin. In the early phases of the immune model, rats presented granular deposits of lgG in the mesangial area with no or descreteproteinuria (<40 mg/24 h). Fibronectin levels in that group were significantly higher (450 ± 90 μg/mL) than in normal rats of the same age (350 ± 46; p < 0.01). When animals presented IgG deposits in the capillary wall, an important nephrotic syndrome developed in most of them. Fibronectin levels then increased very significantly (863 ± 153 μg/mL; p < 0.0005). In the model of adriamycin nephropathy, fibronectin significantly increased (580 ± 110 μg/mL; p < 0.0005) from the first week, when proteinuria was in a range 40–60 mg/24 h. However, the levels were higher (860 ±175 μg/mL; p < 0.0005) when a complete nephrotic syndrome developed. At this time, plasma fibronectin levels correlated directly in both models with the degree of proteinuria and inversely with the total serum protein concentration. Our results show that plasma fibronectin levels increased very early in animals with immune and toxic damage of the kidney. The highest elevated values found thereafter, when a full nephrotic syndrome was present, suggest an increased synthetic rate of that glycoprotein linked to that situation.     

Effects of cyclosporine on adriamycin induced nephropathy

SUMMARY: The effect of cyclosporine on adriamycin nephropathy was studied over both short (6 weeks) and long (26 weeks) periods. In the short-term study, cyclosporine was introduced 2 weeks after nephritis induction and in the long-term study, 14 weeks after the first adriamycin injection. the animals with adriamycin nephropathy treated with cyclosporine, studied for 6 weeks, developed proteinuria with increasd renal size and glomerular area. the nephrotic animals treated with cyclosporine showed less proteinuria than the nephrotic control animals. There were no differences in glomerular area, creatinine clearance or serum creatinine and kidney weight between the treated nephrotic group and the health control group. the nephrotic animals, studied for the longer period, developed intense proteinuria, decreased creatinine clearance, glomerular necrosis and sclerosis, severe tubulointerstitial nephritis, increased hydroxyproline concentration and tubulointerstitial area. No difference was observed between the nephrotic animals treated with cyclosporine and those not treated. In conclusion, Cyclosporine A reduced proteinuria, glomerular hypertrophy and kidney weight in rats with short-term nephropathy but had no effect on the established nephropathy.     

Neutrophil gelatinase-associated lipocalin (NGAL): a new marker of cyclosporine nephrotoxicity?

The aim of work was to investigate whether serum and urinary neutrophil gelatinase-associated lipocalin (sNGAL and uNGAL, respectively) are potential biomarkers of early cyclosporine A (CsA) nephrotoxicity in steroid-dependent nephrotic children (SDNS). The study group (I) consisted of 19 children with SDNS aged 9.46?±?5.52 years treated with CsA. The children were examined four times: at proteinuria relapse, prior to CsA treatment, then after 3, 6, and 12 months of CsA treatment. The control group (II) consisted of 18 healthy children aged 3–15 years. A commercial enzyme-linked immunosorbent assay method was used to measure NGAL concentration. The sNGAL level in SDNS children prior to the administration of CsA was similar to that in the healthy controls (p?>?0.05), but it increased significantly during the course of treatment (p?<?0.01). The uNGAL/creatinine (cr) ratio in SDNS patients was higher before the withdrawal of CsA therapy (p?<?0.05), and was also increased at the consecutive examinations (p?<?0.01). There was a positive correlation between both sNGAL and uNGAL levels and CsA serum level. However, based on the serum and urinary NGAL/cr receiver operating characteristic curve and area under the curve (AUC) analysis, it remains uncertain whether uNGAL is a good predictor of cyclosporine nephropathy. Both sNGAL and uNGAL concentrations increased during the course of CsA treatment. Further studies in larger groups of patients are therefore necessary to confirm our experimental data that increased NGAL levels may be a non-invasive marker for the early detection of tubulointerstitial damage in CsA nephrotoxicity.     

Recovery from cyclosporine-associated arteriolopathy in childhood nephrotic syndrome

Cyclosporine (CS) is well recognized to be effective in the treatment of children with steroid-dependent and steroid-resistant nephrotic syndrome (NS), but its use can result in chronic nephrotoxicity. The histological changes that occur after CS discontinuation are unknown. Therefore, we examined the histological changes [CS-associated arteriolopathy (CAA), tubulointerstitial lesions, and focal glomerular lesions] in renal biopsy specimens after the drug had been discontinued in eight children with idiopathic nephrotic syndrome (NS). These children had been treated with long-term moderate-dose CS and had shown mild-to-moderate chronic CS nephrotoxicity. The degree of CAA improved significantly after CS discontinuation (mean CAA grade from 1.30±0.46 to 0.25±0.46, P=0.028). CAA disappeared in six of these children after CS discontinuation. However, the tubulointerstitial lesions and the focal glomerular lesions did not change after CS discontinuation. In conclusion, in children with idiopathic NS, CAA is improved by discontinuation of CS, but tubulointerstitial changes and focal glomerular lesions do not regress with drug discontinuation. Received: 16 January 2001 / Revised: 26 April 2001 / Accepted: 27 April 2001     

Pregnancy‐Specific Protein B (bPSPB) and Progesterone Monitoring of Post‐Partum Dairy Cows with Placental Retention

The relationship between placental retention, progesterone and pregnancy‐specific protein B (bPSPB) was determined in 60 calving Holstein cows. The cows were divided into two groups with placental retention (WPR, n=16) and no placental retention (NPR, n=44). Every 4 days, until 60 days post‐partum, blood samples were taken and the uteri were checked using ultrasonography. The puerperal characteristics of NPR and WPR were as follows: mean days of abnormal vaginal discharge: 20.2 ± 5 versus 35.6 ± 7 (P < 0.01); mean intervals to uterine involution: 21.4 ± 3.7 versus 27.6 ± 7.6 days (P < 0.01); rate of endometritis: 25 versus 100 % (P < 0.01). The mean numbers of oestrus cycles per cow were 1.75 ± 0.5 versus 0.85 ± 0.9 (P < 0.05) and the mean durations of the first oestrus cycle were 18 ± 3.5 versus 16 ± 2.1 days (P > 0.05). The mean intervals to first ovulation were 21.5 ± 8.4 versus 35 ± 19 days (P < 0.01). bPSPB blood concentrations were higher in the WPR group at calving with 955 ± 170 versus 750 ± 205 ng/ml (P < 0.01) and also during the first 32 days post‐partum with 173.68 ± 47.3 versus 131.0 ± 29.2 ng/ml (P < 0.01). The mean bPSPB half‐life was similar in the two groups: 6.9 ± 2.5 versus 6.5 ± 2.1 days (P > 0.05). In conclusion, it was found that placental retention was associated with a higher rate of endometritis, a lower number of cycles, longer interval to first post‐partum ovulation and higher concentration of bPSPB at calving and during the post‐partum period. The positive relationship between bPSPB concentrations and calf birth weight and their association with post‐partum pathological events may be useful in monitoring animals presenting high concentrations at calving.     

Urinary and glomerular podocytes in patients with chronic kidney diseases

Backgrounds

Podocytes are highly differentiated epithelial cells involved in glomerular filtration. This study determines the clinical and histological significance of podocyte detachment and excretion in urine in patients with chronic kidney diseases.

Methods

Renal biopsy was performed in 59 patients (30 males, 29 females; mean age 48 ± 2 years), including 24 patients with immunoglobulin (Ig)A nephropathy, six each with focal segmental glomerulosclerosis, membranous nephropathy, and minimal change nephrotic syndrome, and 17 with other renal disorders. The number of glomerular podocytes and severity of morphological damage were evaluated in renal biopsy samples. Urinary podocytes were detected by anti-human podocalyxin antibody. The urinary IgG/albumin ratio and urinary peroxide products were assessed by gel electrophoresis and the 2′,7′-dichlorodihydrofluorescein-diacetate method, respectively.

Results

A decrease in glomerular podocytes was associated with age (r = ?0.33; P < 0.05), glomerulosclerosis (r = ?0.43; P < 0.01), tubulointerstitial lesions (r = ?0.46; P < 0.01), and low estimated glomerular filtration rates (r = 0.32; P < 0.05). Increased urinary podocyte excretion correlated with proteinuria (r = 0.36; P < 0.01), and was observed more frequently in patients with active histological lesions. Podocyte loss correlated with lower selectivity of proteinuria in patients with minimal change nephrotic syndrome and focal segmental glomerulosclerosis (r = ?0.90; P < 0.001). Moreover, urinary peroxide products increased in association with glomerulosclerosis (r = 0.39; P < 0.05).

Conclusions

Urinary podocyte excretion reflects ongoing glomerular injury in various kidney diseases, and podocyte loss correlated with glomerulosclerosis and impaired selectivity of proteinuria.     

Treatment of nephrotic idiopathic membranous nephropathy with monthly i.v. pulse cyclophosphamide and oral steroids: a single centre's retrospective study

Aim: While the best treatment of nephrosis‐inducing idiopathic membranous nephropathy (IMN) is controversial, some trials have suggested positive outcomes following treatment with oral cyclophosphamide used in combination with steroids. However, data on i.v. cyclophosphamide plus steroids in treatment of nephrotic IMN are few. Methods: The charts of every patient diagnosed with membranous nephropathy in the Renal Division of Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, from January 2003 to December 2009 (n = 189) were retrospectively analyzed. Patients with nephrotic IMN (n = 32) were treated with monthly i.v. cyclophosphamide (500–750 mg/m²) and oral prednisone for at least 6 months. Efficacy as well as safety and tolerability of this regimen were evaluated. Result: Thirty‐two patients with nephrotic IMN (56% male, age 51.5 ± 12.6 years, estimated glomerular filtration rate 73.7 ± 20.0 mL/min per 1.73 m²) were included in our study. During the median follow‐up duration of 30.0 (12.5–42.8) months, 40.6% of patients achieved complete remission, while 40.6% achieved partial remission. Relapse occurred in five patients in a median of 16 (11.5–26) months after cessation of immunosuppressive treatment. No patients developed renal insufficiency during the follow up, while 16 side‐effects were noted in 10 patients. Complete remission rates at 3, 6 and 15 months were 0%, 12.5% and 40.6% and remission rates were 21.9%, 68.8% and 81.2%, respectively. Complement 3 deposition was significantly associated with the probability of non‐remission. Conclusion: Monthly i.v. pulse cyclophosphamide plus oral steroids may be an alternative treatment option in Chinese patients with nephrotic IMN.     

IgA肾病肾病综合征临床病理特点及肾脏病理危险因素

目的：探讨IgA肾病肾病综合征患者临床病理特点及肾脏病理损害的危险因素。方法：选择1987年～2006年经肾活检确诊IgA肾病并表现为肾病综合征的患者118例，分析其临床病理特点，按肾脏病变轻重分为A组（n=34，包括Lee氏分级Ⅰ级、Ⅱ级）、B组（n=84，Ⅲ、Ⅳ、Ⅴ级），比较两组临床指标，并多因素分析影响肾脏病理损害的危险因素。结果：A、B两组高血压分别占11．8％ vs 63．1％；肾衰竭分别占15％ vs 41．7％；A、B两组尿蛋白≥6g／24h者分别占58．8％ vs 32．1％；尿红细胞满视野分别为14．7％ vs 50％。A组高血压、肾衰竭、镜下尿红细胞满视野发生率显著低于B组（P〈0．01），尿蛋白≥6g／24h发生率显著高于B组（P〈0．01）。A组平均动脉压、血肌酐明显低于B组（P〈0．01）；而尿蛋白定量、血红蛋白显著高于B组（P〈0．05）。多因素分析显示IgA肾病肾病综合征患者肾脏病理损害重的危险因素有平均动脉压、尿蛋白〈6g／24h、镜下尿RBC〉5．0×10^7／L（0R值分别为1．048，3．227，6．578；P值分别为0．034，0．047，0．002），血红蛋白是保护性因素（OR=0.723，P=0．035）。随着平均动脉压的升高、血红蛋白的降低、镜下尿红细胞数的增多，肾脏病理损害程度加重（P〈0．01）。结论：IgA肾病肾病综合征患者临床、病理表现存在差异，高血压、血红蛋白水平、24h尿蛋白排泄量、镜下尿红细胞程度有助于判断肾脏病理损害轻重。     

Ischemia/reperfusion‐induced necrosis and apoptosis in the cells isolated from rat skeletal muscle

Necrosis was considered to be the solo mechanism for ischemia/reperfusion (I/R)‐induced cell death. Recent evidence from I/R models of the heart, liver, kidney, and brain indicates that apoptosis is a major contributor to I/R‐induced cell death. However, evidence of I/R‐induced apoptosis in skeletal muscle is sparse and divided. The purpose for the present study was to investigate I/R‐induced necrosis and apoptosis in the cells isolated from rat skeletal muscle. A rat gracilis muscle model was used. After surgical preparation, clamps were applied on the vascular pedicle to create 4 h of ischemia and released for 24 h of reperfusion (I/R, n = 10). Clamping was omitted in sham I/R rats (sham I/R, n = 10). The muscle samples were harvested after 24 h of reperfusion for the process of cell isolation. Cells were stained by Propidium Iodide (PI) or Annexin V‐FITC or both. Twenty thousand cells from each muscle sample were scanned and analyzed by flow cytometry. The average percentage of live cells was 45 ± 2% in the I/R group versus 65 ± 3% in the sham I/R group (p < 0.01). The average percentage of necrotic cells was 18 ± 1% in I/R versus 12 ± 1% in sham I/R (p < 0.01). The average percentage of apoptotic cells was 40 ± 3% in I/R versus 27 ± 3% in sham I/R (p < 0.01). Our results clearly demonstrated that I/R not only causes necrosis, but also accelerates apoptosis in the cells isolated from rat skeletal muscle. © 2007 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 26:351–356, 2008     

Rekombinanter Faktor VIIa in der Hämorrhagiebehandlung des Schwerstverletzten

Background

The aim of the study was to assess whether the use of recombinant factor VIIa (rFVIIa) in trauma patients was associated with improved outcome.

Patients and methods

Patients documented in the TraumaRegistry of the German Society for Trauma Surgery (primary admissions; Injury Severity Score, ISS≥?9) who received rFVIIa in the first 6 hours upon admission (rFVIIa?+) were matched with patients that had not received rFVIIa (rFVIIa?).

Results

The matching comparison yielded two identical groups with 100 patients each (rFVIIa+: average age 40.6±18.5 years, ISS 47.1±16.7 versus rFVIIa─: 40.1±19.1 years, ISS 45.1±15.6). Patients were administered an average of 18.3±13.1 (rFVIIa+) versus 19.5±14.0 (rFVIIa─) red blood cell units (p=0.55) and 15.2±13.7 (rFVIIa+) versus 15.0±13.1 (rFVIIa─) units of fresh frozen plasma (p=0.92). Thromboembolisms occurred in 5% (rFVIIa+) versus 2% (rFVIIa─) (p=0.44), multiple organ failure (MOF) in 82% versus 62% (p=0.003) and hospital mortality was 48% versus 43% (p=0.57), respectively.

Conclusion

The early use of rFVIIa in severely injured patients was not associated with either lower transfusion requirements or with mortality reduction but with increased MOF.     

Effect of cyclosporine on adriamycin induced nephritis

The effects of cyclosporine A (CSA) administration, started as early as renal lesion is induced, on the development of Adriamycin-induced nephropathy were assessed by comparing the time course of this nephropathy in rats receiving CSA with that in non-treated animals (group ADR) over 16 weeks. Throughout the experiment, no significant difference in proteinuria was observed between the groups. At the end of the experiment, there was no significant difference between the groups regarding the frequency of glomerular lesion (Group AADR: Md = 23%, P25 = 15%, P75 = 75%; Group ADR-CSA: Md = 48%, P25 = 11%, P75 = 70%); tubulointerstitial lesion index (Group ADR: Md = 1.5, P25 = 1.0, P75 = 2.5); glomerulosclerosis area (Group ADR = 18.2 +/- 4.2%; Group ADR-CSA = 13.2 +/- 1.4%); and, interstitial fibrosis area (Group ADR+V: 1.75 +/- 0.10%; group ADR-CSA: 1.34 +/- 0.09%). In conclusion, CSA, when administered since nephropathy induction does not change the course of the disease.     

贫血加重IgA肾病患者的临床和病理改变

目的 分析IgA肾病合并贫血患者的临床病理特征.方法 收集经肾活检确诊的IgA肾病患者临床资料409例,按照贫血与否分为非贫血组和贫血组,回顾性分析两组患者的临床和病理资料.结果 与非贫血组比较,贫血组患者的肾小球损伤和肾小管间质萎缩程度较重、24 h尿蛋白增多和eGFR降低.Spearman相关分析结果显示,血红蛋白、eGFR与肾脏病理损伤呈负相关(P＜0.05),血尿酸、24h尿蛋白与肾脏病理损伤呈正相关(P＜0.05).多因素Logistic回归分析发现贫血是肾小管间质萎缩的独立危险因素.结论 IgA肾病合并贫血患者的临床和病理损伤重于IgA肾病非贫血的患者,贫血参与IgA肾病的进展.     

Effects of buffering in hypercapnia and hypercapnic hypoxemia

Anesthetized, paralyzed and mechanically ventilated pigs were exposed to extreme hypercapnia (Paco_2-20 kPa) at Fio₂ 0.4 for 480 min, with (n = 6) or without (n = 6) continuous infusion of isotonic buffers (bicarbonate and trometamol). Arterial pH was higher in buffered animals than controls, 7.21 ±0.01 vs 7.01±0.01 (mean ± s.e.mean, P < 0.01). Serum osmolality and Paco₂ did not differ between groups throughout the experiment. The hemodynamic response to hypercapnia was attenuated in the buffered group, who had lower heart rate, 133 ± 6 vs 189±12 min^-1 (P < 0.01), mean arterial pressure (MAP) 109 ± 4 vs 124 ± 4 mmHg (14.5 ± 0.5 vs 16.5 ± 0.5 kPa) (P < 0.05), mean pulmonary arterial pressure 16±1 vs 23 ± 1 mmHg (2.1 ±0.1 vs 3.1 ±0.1 kPa) (P < 0.01), and pulmonary vascular resistance (PVR) 249 ± 21 vs 343 ± 20 dyn s-cm^-5 (2490±210 vs 3430±200 μN-s-cm^-5) (P < 0.01), compared with the control group. Subsequently, both groups were exposed to hypercapnic hypoxemia by stepwise increases in Fio₂ (0.15, 0.10, 0.05) at 30-min intervals, while Fico₂ was kept at 0.2. PVR increased in both groups (P < 0.05) but, except for heart rate, all hemodynamic differences between the groups disappeared during hypoxia. At Fio₂ 0.15, buffered animals had higher arterial oxygen saturation (73 ± 5%) than the controls (55 ± 5%), (P < 0.05). The control animals died after 1–29 min (mean 14 min) at Fio₂ 0.10, while all buffered animals survived Fio₂ 0.10 with stable MAP (122 ± 14 mmHg (16.3 ± 1.9 kPa). The buffered animals died after 4–22 min (mean 15 min) at Fio₂ 0.05. We conclude that buffering to a pH of 7.21 attenuates the observed hemodynamic response in extreme hypercapnia and improves survival in hypercapnic hypoxemia.     

Applicant perceptions of new selection systems are a function of their performance in the selection procedure

Introduction

Screening practices for selecting surgery trainees have been criticized for subjectivity, inefficiency, and inability to predict performance. This study explored applicant perceptions to an untraditional selection process.

Aluminum-Induced Osteogenesis in Osteopenic Rats with Normal Renal Function

Previous studies have shown a different effect of aluminum (Al) on bone metabolism in animals with chronic renal failure and conversely, positive osteogenic effects in animals with normal renal function. The aim of this study was to evaluate the effect of aluminum on bone metabolism in osteopenic rats. We studied male Wistar rats with severe osteopenia induced by adding NH4Cl (2%) to the drinking water over a 6-month period. The rats were divided into two groups and followed for 4 months. The Aluminum group (G1) received AlC13 intraperitoneally (10 mg/kg/5 days/week) (n = 8); the Control group (G2) did not receive any treatment after stopping the administration of NH4Cl (n = 5). In all animals we measured biochemical markers (serum Ca, P, Cr, Al, osteocalcin, hydroxyproline) as well as bone mineral density and bone histomorphometry (BV/TV, CTh, ObS/BS, OTh, and NOc/TV). Bone aluminum content, measured by atomic absorption spectrometry, was 101.6 ± 13 μg/g in the Al overloaded group and 1.31 ± 0.14 in controls. Bone mineral density, evaluated by dual X-ray absorptiometry (DXA) at the proximal extremity of the tibia was significantly higher in G1 (0.292 ± 0.01 g/cm² versus 0.267 ± 0.02 g/cm²). No significant differences were found between the biochemical markers. In the histomorphometric parameters we observed significant differences in G1 compared with G2: an increase in BV/TV (18.59 ± 5.6 versus 7.69 ± 3.08%) and in CTh (0.52 ± 0.06 versus 0.36 ± 0.07 mm) with a moderate increment of the osteoid thickness (14.05 ± 4.72 versus 5.25 ± 0.9 μm) (P < 0.05). Changes in others parameters and the relationship between biochemical parameters of bone remodeling, Al, and histology were analyzed. These findings indicate that in rats with normal renal function, Al is able to induce bone formation even when osteopenia is present. Received: 23 December 1996 / Accepted: 2 September 1997     

A prospective study on the use of mycophenolate mofetil in children with cyclosporine-dependent nephrotic syndrome

Cyclosporine A (CsA) has relieved children with steroid-dependent nephrotic syndrome (NS) from steroid toxicity. However, most patients frequently relapse again when CsA is withdrawn, resulting in the development of CsA nephropathy for its long-term use. In order to assess the efficacy of mycophenolate mofetil (MMF) therapy, we prospectively analyzed 12 children with idiopathic steroid-dependent NS requiring long-term CsA therapy with MMF for at least 6 months. Mean follow-up after starting MMF was 11 months (range 6–42). The mean MMF dose required was 610±95 mg/m²/12 h, which maintained mean predose mycophenolic acid (C0-MPA) levels of 2.4±1.1 mcg/ml. Treatment with MMF resulted in CsA and/or prednisolone (PSL) sparing, with a reduction in mean CsA dose from 3.5±1.3 to 1.5±2.4 mg/kg/day (p<0.01), and mean PSL dose from 0.29±0.16 to 0.21±0.11 mg/kg/day (p<0.05). Nine of 12 patients (75%) were finally able to be weaned off CsA. Mean relapse rates decreased from 2.7±1.6 to 0.6±0.9 episodes/year (p<0.01). Relapse-free ratio on MMF therapy was lower in patients whose average C0-MPA levels were less than 2 mcg/ml (p<0.05). Our experience demonstrates that MMF therapy results in significant CsA and/or steroid sparing and reduction in relapse rates in children with CsA-dependent NS.     

Urinary 3H-Tetracycline and Pyridinium Crosslinks Differ in Their Response to Calcium Restriction in Mature and Aged Rats

The aim of this study was to evaluate bone resorption (BR) in rats by two methods: chronic ³H-tetracycline labeling (³HTC) and pyridinium crosslink excretion (PYDX), and compare the sensitivity of these markers in two age groups. Female Sprague-Dawley rats at 12–29 weeks of age (``mature', n = 12) and at 40–57 weeks of age (``aged', n = 22) were examined. Skeletal incorporation of ³HTC in aged rats was 43 ± 8% of that in mature animals (P < 0.01), indicating an age-related decrease in bone turnover. BR was modulated over 9 weeks by calcium restriction (CR), measured by urinary excretion of both ³HTC and PYDX, and compared with age-matched, calcium-adequate controls. At baseline, urinary excretion of ³HTC was not significantly different between age groups, whereas urinary PYDX was 14–20% higher in mature compared with aged rats (P < 0.01). CR produced a 32–39% peak increase in BR (P < 0.01) compared with controls that did not differ significantly between marker or age group. Urinary ³HTC was elevated at weeks 1–3 (P < 0.01) and reached maximal values at week 2 (32 ± 17%). Urinary PYDX, however, was not elevated until week 2, reached maximal levels at week 3 (39 ± 15%), and remained elevated until week 6 (P < 0.01). These data indicate that although both markers are elevated by CR, marker response differs with age, and variability exists for acute and chronic responses. Received: 6 February 1998 / Accepted: 1 October 1998     

263例成人原发性局灶节段肾小球硬化性肾小球肾炎临床病理分析

目的 了解我国南方地区原发性局灶节段肾小球硬化性（FSGS）肾小球肾炎的发病情况及探讨FSGS临床与病理特征的关系。方法 收集1988年7月至2005年7月经我院肾活检确诊为原发性FSGS的263例成人患者的临床及肾脏病理资料并进行分析。 结果 （1）原发性FSGS占同期成人原发性肾小球疾病 7.02%,占成人原发性肾病综合征（NS）6.33%，其构成比近年有逐渐升高的趋势。青壮年为成人FSGS的主要患病人群，临床以不同程度的蛋白尿为特征，以NS为主要临床表现的有133例，占50.6%。（2）主要病理特征： 48.4%患者肾小球硬化比率≥25%，肾小球硬化并伴有肾小管间质病变者占88.6%，其中伴严重肾小管间质病变占25.2%。（3）肾小球硬化程度及小管间质病变程度与Ccr呈负相关 (P ＜ 0.01），并与Scr水平呈正相关(P ＜ 0.05）。肾小球硬化程度与小管间质病变程度呈正相关(P ＜ 0.01），与血浆白蛋白水平呈正相关(P ＜ 0.05）。肾小管间质病变是FSGS患者出现肾功能不全的重要影响因素。结论 原发性FSGS是成人肾病综合征的主要病理类型之一，就诊时肾小球硬化及肾小管间质纤维化已损害明显，并与肾功能损害密切相关。早期诊断和及时治疗，从而延缓FSGS的进展仍是广大肾脏病工作者探索的重要课题。