Effects of mTOR inhibitor–related proteinuria on progression of cardiac allograft vasculopathy and outcomes among heart transplant recipients

We have previously described the use of sirolimus (SRL) as primary immunosuppression following heart transplantation (HT). The advantages of this approach include attenuation of cardiac allograft vasculopathy (CAV), improvement in glomerular filtration rate (GFR), and reduced malignancy. However, in some patients SRL may cause significant proteinuria. We sought to investigate the prognostic value of proteinuria after conversion to SRL. CAV progression and adverse clinical events were studied. CAV progression was assessed by measuring the Δ change in plaque volume (PV) and plaque index (PI) per year using coronary intravascular ultrasound. Proteinuria was defined as Δ urine protein ≥300 mg/24 h at 1 year after conversion to SRL. Overall, 137 patients were analyzed (26% with proteinuria). Patients with proteinuria had significantly lower GFR (P = .005) but similar GFR during follow-up. Delta PV (P < .001) and Δ PI (P = .001) were significantly higher among patients with proteinuria after adjustment for baseline characteristics. Multivariate Cox regression analysis showed higher all-cause mortality (hazard ratio 3.8; P = .01) with proteinuria but similar risk of CAV-related events (P = .61). Our results indicate that proteinuria is a marker of baseline renal dysfunction, and that HT recipients who develop proteinuria after conversion to SRL have less attenuation of CAV progression and higher mortality risk.     

Renal functional reserve in children with reduced renal mass: study by two dietary periods

It has been suggested that the renal functional reserve (RFR) defined by the rise in glomerular filtration rate (GFR) after a protein load could disappear in patients with severe nephron loss but with a normal GFR. This study compared, in 17 children, inulin clearance (C _in) measured by the plasma inulin plateau at the end of two 14-day randomized periods differing in protein intake: 100% (low protein, LP), or 200% (high protein, HP) of recommended dictary allowances (RDA). Diets were aimed at maintaining food habits and energy intake. Compliance was assessed by records of the last 3–4 days, an interview with the dietician and by urinary nitrogen measurements. Mean actual protein intake was 109% (56%–139%) RDA for the LP period and 220% (163%–319%) RDA for the HP period.C _in did not change in 14 children with GFR below (n=7) or within (n=7) the normal range.C _in was higher in the HP period than in the LP period (+32, 50, 63%) in 3 children who had a 50% (single kidneys) or a 25% (sclerosed glomeruli) nephron loss. Non-responding children had a GFR below 105 ml/min per 1.73 m². Nephron loss (70% sclerosed glomeruli) was estimated in only 1 child with no RFR. The results suggest that GFR measurement after prolonged dietary stimulation could help in evaluating the severity of nephron loss in children with normal or borderline GFR. The prognostic value of this test has to be confirmed by long-term follow-up.     

短期使用苯那普利对肾小球滤过膜通透性的影响

目的 :研究肾小球滤过膜对不同分子量蛋白质通透性能对苯那普利短期治疗的反应性。方法 :根据聚丙烯酰胺凝胶电泳和 2 4小时尿蛋白定量 ,计算出大分子量和中分子量尿蛋白排泄量。口服苯那普利 10mg/d ,共两天 ,测定用药前后2 4小时尿蛋白总量、尿蛋白圆盘电泳、平均动脉血压等。结果 :用药后大分子尿蛋白、平均动脉血压明显降低 ( 1.15± 0 .89)g/ 2 4hvs ( 0 .84± 0 .74)g/h ,P <0 .0 1;( 14 .19± 1.96)kPavs ( 12 .76± 1.12 )kPa ,P <0 .0 1) ,2 4小时尿蛋白总量、中分子尿蛋白数减少无显著性 ( 3 .16± 2 .2 4)g/ 2 4hvs ( 2 .83± 2 .2 7) g/ 2 4h ,P >0 .0 5 ;( 1.72± 1.2 2 )g/ 2 4hvs ( 1.62± 1.47) g/ 2 4h ,P >0 0 5 )。结论 :短期使用苯那普利可改善肾小球滤过膜对大分子蛋白的通透性。     

Measurement of the ratio of glomerular filtration rate to plasma volume from the technetium-99m diethylene triamine pentaacetic acid renogram: comparison with glomerular filtration rate in relation to extracellular fluid volume

Individual kidney glomerular filtration rate (IKGFR) can be measured from the renogram from the rate of uptake of technetium-99m diethylene triamine penta-acetic acid (^99mTc-DTPA). A blood sample is required to derive IKGFR in millilitres per minute, which is then usually normalised to body surface area. We describe a technique which does not require a blood sample, is already normalised for plasma volume and uses the robust Patlak plot for measuring renal uptake. The rate of kidney uptake, dR(t)ldt, at time = 0, as a fraction of the injected dose, is equal to the fraction of the plasma volume (PV) filtered per minute, i.e. IKGFR/PV. The gradient dR(0)/dt cannot be accurately measured directly but is equal to [ · LV(0)], where is the renal uptake constant (proportional to IKGFR) and LV is the count rate over a left ventricular ROI. LV(0) was obtained by extrapolation of LV(t), while a is the slope of the Patlak plot up to 3 min. GFR/PV (i.e. right plus left kidneys) in patients with normal renal function was about 0.04 min^–1, as would be expected from normal values of GFR (120 ml/min) and plasma volume (3 l). GFR/PV correlated significantly with the ratio of GFR to extracellular fluid volume (ECV), measured from the terminal exponential of the plasma clearance curve (GFR/PV = 3.2.GFR/ECV + 5.3 ml/min/1 [r = 0.82,n = 82]). GFR/PV (r = 0.74) and GFR/ECV (r = 0.82) both correlated inversely and non-linearly with plasma creatinine in 43 studies where the measurement was made within 1 week of the^99mTcDTPA study. They also correlated significantly with the plasma cyclosporin trough level in 14 patients with dermatomyositis on the 30 occasions when this measurement was made within 1 week of the renogram (r = –0.38,P < 0.05 for GFR/PV andr = –0.77,P < 0.001 for GFR/ECV). The ratio of GFR/PV to GFR/ECV is the ratio of extracellular fluid volume to plasma volume, and this was 4.0 (SD 0.99). We conclude that both GFR/PV and GFR/ECV can be easily measured with^99mTc-DTPA and are physiologically valid expressions of GFR. Although GFR/PV and GFR/ECV correlate with each other, the question is raised as to which of the two fluid volumes is the most appropriate for normalising GFR. Correspondence to: A.M. Peters     

Influence of serum albumin on renal function in nephrotic syndrome

 Glomerular filtration rate (GFR) and effective renal plasma flow (ERPF), determined by the clearances of inulin and para-aminohippuric acid, were evaluated in 119 children with different types of nephrotic syndrome and in different stages: the nephrotic stage (serum albumin <25 g/l), recovery stage (25–35 g/l), and remission (>35 g/l). GFR in the nephrotic stage was significantly lower than in remission and in controls, and was lowest at onset of the disease (84±6, 111±4, and 119±2 ml/min per 1.73 m²). ERPF was higher in the nephrotic stage than in recovery, especially in children with histological lesions. Thus the filtration fraction (FF) was greatly decreased in the nephrotic stage. In patients investigated both in the nephrotic and the remission phase, GFR and FF increased significantly. There was a direct correlation between the serum albumin concentration and FF and an inverse correlation between mean arterial pressure (MAP) and GFR and FF in all patients, a direct correlation between the serum albumin concentration and GFR in minimal change nephrotic syndrome patients, and an inverse correlation between ERPF and serum albumin in children with histological lesions. In conclusion, GFR and FF were decreased and ERPF increased in the nephrotic stage, normalizing in remission. The low GFR in the nephrotic stage was thus not dependent on hypoperfusion. We suggest that the low GFR is dependent on a very low ultrafiltration coefficient. The direct correlation between GFR and serum albumin and the indirect correlation between GFR and MAP suggest compensatory mechanisms that increase the ultrafiltration pressure to counteract the severely reduced ultrafiltration coefficient. Received: 19 November 1997 / Revised: 11 April 1998 / Accepted: 14 April 1998     

Efficiency of Superfine Glass Fiber Membrane\= Filters for Depleting Leukocytes

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5-Fu抑制兔眼滤过道成纤维细胞的AgNORs表达

目的　应用细胞增殖指标AgNORs,研究兔眼滤过道成纤维细胞 (Fb)增殖规律及 5 Fu的抗增殖作用。方法　取兔眼滤过道切片作AgNORs及HE染色 ,比较 5 Fu眼和对照眼FbAgNORs染色颗粒数量。结果　对照眼滤过道的咬切口、巩膜瓣下、结膜瓣下均有Fb增殖 ,且增殖活性第 7天最高 ,第 3 0天最低。 5 Fu眼FbAgNORs颗粒数显著低于对照眼 ,5 Fu抑制率为 44.9%～ 73 .0 %。结论　 5 Fu可以有效抑制咬切口、巩膜瓣下、结膜瓣下Fb的增殖活性     

An Experimental Study on Homoharringtonine Liposome and Glaucoma Filtration Surgery

Purpose: To observe the inhibitory action of homoharringtonine liposome during the healing process of wounds in the filtering sitesMethods: posterior sclerectomies were performed in 14 rabbits. Postoperatively one eye of each rabbit received subconjunctival injections of HH liposome and fellow eye received saline injection in a randomized masked fashion.Results; Fourteen days after operation the IOP of experimental eyes reduced significantly (P < 0.01) as compared with the controlled eyes, and the number of remaining filtering blebs increased noticeably (P< 0.05). Pathohistological examination revealed that the number of fibroblasts per square micron in the filtering sites and the thickness of the scars in the center of the filtering sites of the experimental eyes were less than those of the controlled eyes. No serious ocular toxic and side effects were found.Conclusion : This experiment suggests that homoharringtonine liposome can markedly inhibit the scar formation of filtering sites after glaucoma fi