Tocilizumab en el tratamiento del rechazo humoral crónico activo resistente a terapia estándar

IntroductionThere is no consensus on the most appropriate treatment for chronic active antibody-mediated rejection (cAMR). Recent studies suggest that treatment with tocilizumab (TCZ) may stabilize graft function, decrease the intensity of donor-specific HLA antibodies (DSAs) and reduce inflammation of microcirculation.Patients and methodsObservational study with renal allograft recipients diagnosed with cAMR (n = 5) who had not submitted a response to traditional treatment based on the combination of plasma replacements, immunoglobulins, and rituximab. Patients were told to be treated with TCZ as compassionate use in six doses per month (8 mg/kg/month). Renal function, proteinuria, and the intensity of DSAs were monitored during follow-up.ResultsFive patients, average age 60 ± 13 years, three male and two retrasplants (cPRA average 55%) with preformed DSAs. Treatment with TCZ was initiated within 47 ± 52 days of biopsy. In two cases treatment was discontinued after the first dose, by severe bicitopenia with cytomegalovirus viremia and by graft failure, respectively. In the three patients who completed treatment, no stability of renal function (serum creatinine from 1.73 ± 0.70 to 2.04 ± 0.52 mg/dL, e-FGR 4 6 ± 15 to 36 ± 16 mL/min), showed increased proteinuria (3.2 ± 4.0 to 6.9 ± 11.0 g/g) and the intensity of DSAs maintain stable. No changes were observed in the degree of inflammation of microcirculation (g + pt 4.2 ± 0.8 vs. 4.3 ± 1.0) or in the degree of transplant glomerulopathy (cg 1.2 ± 0.4 vs. 1.8 ± 1.0).ConclusionsTCZ therapy does not appear to be effective in modifying the natural history of chronic active antibody-mediated rejection, does not improve the degree of inflammation of microcirculation and does not reduces the intensity of DSAs.     

Predicting Renal Function Outcomes After Partial and Radical Nephrectomy

Background

Partial nephrectomy (PN) is generally favored for cT1 tumors over radical nephrectomy (RN) when technically feasible. However, it can be unclear whether the additional risks of PN are worth the magnitude of renal function benefit.

Glomerular lesions in adolescents with gross hematuria or the nephrotic syndrome

We report clinical and pathological data in 56 adolescents presenting with gross hematuria (GH) and 65 presenting with idiopathic nephrotic syndrome (INS). IgA nephropathy (present in 52%) and other mesangial lesions were found in the majority of the 56 patients with GH. Many of these patients had complex urological procedures prior to consideration of a nephrological problem. This often led to significant delays in making the appropriate diagnosis. Pathological lesions in the 65 patients with INS included minimal change NS (MCNS) in 31%, membranous glomerulonephritis (MGN) and focal segmental glomerulosclerosis (FSGS) in 18.5% each, and membranoproliferative GN (MPGN) in 12%. In 47 of the patients with INS, in whom no specific treatment had been given prior to renal biopsy, MCNS and MGN were observed with a similar frequency (26% and 23%, respectively), with FSGS and MPGN being found in 21% and 11%. These results indicate that the pathological lesions in adolescents with INS who undergo a renal biopsy more closely resemble those in adults, and are usually more severe than those in young children. However, it should be noted that our study was retrospective. Hence, there were probably some adolescents with INS who had a successful response to therapy and therefore did not have a renal biopsy performed. Southwest Pediatric Nephrology Study Group (Central Office, Baylor University Medical Center at Dallas, Tex., USA). Director, Ronald J. Hogg; Associate Directors, Fred G. Silva and F. Bruder Stapleton; Statistician, Joan S. Reisch; Administrative Assistant, Kaye Green. Participating Centers—Baylor College of Medicine, Houston, Tex.: Phillip L. Berry, L. Leighton Hill, Sami A, Sanjad, Edith Hawkins; Baylor University Medical Center, Dallas, Tex.: Ronald J. Hogg, Kaye Green; Tulane University Medical Center, New Orleans, La.: Frank Boineau, John E. Lewy, Radhakrishna Baliga, Patrick Walker; University of Arkansas, Little Rock, Ark.: Watson Arnold, Eileen Ellis, Edward Uthman; University of Colorado Health Science Center, Denver, Colo.: Gary M. Lum, Wiliam Hammond; University of Oklahoma Medical Center, Oklahoma City, Okla.: James Wenzl, James Matson, Geoffrey Altshuler, Sarah Johnson; University of Tennessee, Memphis, Tenn.: F. Bruder Stapleton, Shane Roy, III, Robert J. Wyatt, Charles McKay, William Murphy; University of Texas Health Science Center at Dallas, Tex.: Billy S. Arant Jr, Michel Baum, Fred G. Silva, Arthur Weinberg, Craig Argyle, Joseph Rutledge, Ed Eigenbrodt; University of Texas Medical School, Houston, Tex.: Susan B. Conley, Jacques Lemine, Ron Portman, Ann Ince, Regina Verani; University of Texas Health Science Center at San Antonio, Tex.: Michael Foulds, Sudesh Makker, Kanwal Kher, Melanie Sweet, Victor Saldivar, Fermin Tio; University of Texas Medical Branch, Galveston, Tex.: Ben H. Brouhard, Alok Kalia, Luther B. Travis, Lisa Hollander, Tito Cavallo, Srinivasan Rajaraman; University of Utah Medical Center, Salt Lake City; Utah: Eileen Brewer, Richard Siegler, Elizabeth Hammond, Theodore Pysher. Note that this list reflects the investigators' addresses and positions during the period of this study and not necessarily their current situations.     

Factors related to renal haemodynamics in young type-1 diabetes mellitus patients

The influence of metabolic control (HbA_1c), noradrenaline (NA) and insulin-like growth factors (IGF-I and IGF-II) on renal function and size was investigated in 11 insulin-dependent diabetes mellitus patients aged 11–17 years. Renal function was evaluated in terms of glomerular filtration rate (GFR) and effective renal plasma flow (ERPF). Renal size was determined as renal parenchymal volume (RPV) by ultrasonography. The patients' HbA_1c values ranged from 8.2% to 12.9% (normal range 5.5–8.5%) and their GFR and ERPF were higher than normal. Their IGF-II values were higher, and NA and IGF-I levels were lower than those of healthy controls. Inverse correlations between NA and GFR (r=–0.66) and NA and ERPF (r=–0.63) were found. No correlation was found between serum IGF-I and renal functional parameters. The IGF-II values correlated with GFR and HbA_1c (r=0.63,r=0.70 respectively). There were linear correlations between RPV and GFR, RPV and ERPF, HbA_1c and GFR, and ERPF and RPV. Decreased NA concentrations and increased IGF-II values appear to be factors contributing to renal hyperfunction in these patients.     

脂蛋白（a）对肾小球系膜细胞的作用

目的探讨脂蛋白（ａ）［Ｌｐ（ａ）］对肾小球系膜细胞（ＧＭＣ）的作用。方法将体外培养的系膜细胞，加脂蛋白（ａ）刺激后，测定细胞生长率和细胞上清中血小板活化因子（ＰＡＦ）、肿瘤坏死因子（ＴＮＦ）、乳酸脱氢酶（ＬＤＨ）及纤维连结蛋白（ＦＮ）水平，并以未经刺激者作对照。结果经脂蛋白（ａ）刺激４８小时，在终浓度５～２０ｍｇ／Ｌ时细胞生长率轻度增加，而在５０～４００ｍｇ／Ｌ时细胞生长率明显下降。刺激１８小时，细胞上清中ＰＡＦ的水平明显高于对照，且与脂蛋白（ａ）浓度呈明显正相关（ｒ＝０．９３７，Ｐ＜０．０１）；Ｌ９２９细胞的杀伤率有所增加，但未达５０％；ＬＤＨ的水平在脂蛋白（ａ）１００ｍｇ／Ｌ以下时有所增加；刺激１８、４８、７２小时后的细胞上清纤维连结蛋白均为阴性。结论脂蛋白（ａ）对系膜细胞体外增殖有低浓度轻度促进、高浓度抑制的双向作用，对细胞ＰＡＦ的产生具有浓度依赖的促进作用，并能增加细胞上清中ＬＤＨ及ＴＮＦ水平，因而可通过多种途径介导肾小球损伤。     

雷帕霉素对炎性反应状态下肾小球系膜细胞内脂质稳态的影响

Objective To investigate the effect of rapamycin on cholesterol homeostasis of glomerular mesangial cells and the underlying mechanism. Methods Glomerular mesangial cell line (HMCL) cells were cultured and divided into control group, IL-1β group and different concentration rapamycin groups. Intracellular cholesterol accumulation was observed and measured by oil O staining and HPLC. Real-time quantitative PCR and Western blot were used to detect the mRNA and protein expression of LDLR, PPARγ, LXRα, ABCA1 in HMCL after the treatment with IL-1β and rapamycin. Results Rapamycin had no significant influence on intracellular cholesterol concentration under normal condition. IL-1β significantly increased the intracellular cholesterol concentration by 143％ of control (P<0.05), and 10, 50, 100 ?滋g/L rapamycin could significantly inhibit the effect of IL-1β (87％, 116％, 96％ of control respectively, all P<0.05). Rapamycin could suppress the increased expression of LDLR caused by IL-1β on both mRNA and protein level in a dose-dependent manner（P<0.01）. Rapamycin dose-dependently up-regulated the reduced mRNA and protein expression of ABCA1, the decreased mRNA expression of PPARγ and LXRα induced by IL-1β as well (P<0.01）. Conclusion Rapamycin may contribute to the maintenance of intracellular cholesterol homeostasis in glomerular mesangial cells under inflammatory state by both reducing cholesterol uptake and promoting cholesterol efflux.     

血清胱抑素C对高血压和糖尿病早期肾功能损伤的诊断价值

目的探讨血清胱抑素C(Cys-C)水平对高血压、糖尿病早期肾功能损害的临床价值。方法收集22例高血压患者、28例糖尿病患者及44例肾病患者的血清标本,用酶法测定血清肌酐、尿素氮,用颗粒增强免疫比浊法测定血清Cys-C,放射免疫法测定β2-微球蛋白。结果血清Cys-C和β2-微球蛋白的异常检出率显著高于血清肌酐、尿素氮;高血压及糖尿病两组患者血清Cys-C水平均较正常对照组明显升高(P<0.01);肾病组各项检测指标均显著高于高血压组、糖尿病组和正常对照组。结论对早期肾功能损害的诊断价值,血清Cys-C测定敏感性稍次于β2-微球蛋白,但其特异性优于血清β2-微球蛋白,综合比较,血清Cys-C可作为高血压及糖尿病早期肾功能损害的辅助诊断指标之一。     

Hemangioma of the Prostatic Urethra: Hematospermia and Massive Postejaculation Hematuria with Clot Retention

The case of a 53-year-old man with hematospermia and massive postejaculation hematuria that caused urinary retention is described. This is the sixth case in the English and Japanese language literature. Cystourethroscopic examination revealed that a solitary raised tumor was present just distal to the vermontanum, and that bleeding was from its apex. Histologic examination of an excisional biopsy sample showed features compatible with hemangioma.     

Renal regulation of salt balance: a primer for non-purists

The greater than 40-fold range of voluntary salt intake in humans requires corresponding adjustments in renal excretion to maintain balance. Although many mechanisms have been implicated in the regulation of salt output by the kidney, surprisingly little consideration has been given to their quantitative significance and possible interaction. This survey summarizes the effects of changes in glomerular filtration rate, proximal peritubular physical factors, and plasma concentrations of aldosterone and atrial natriuretic factor (ANF), singly and in combination, on the level of salt excretion. Contrary to expectation, even large increases in filtration or decreases in proximal reabsorption have only minor natriuretic effects, due to constancy of fractional reabsorption in downstream nephron segments. Lack of aldosterone release increases salt excretion as much or more than the upstream mechanisms, whereas ANF-induced inhibition of reabsorption in the medullary collccting duct has the largest effect. It may be concluded, therefore, that the potency of these natriuretic factors increases with distance along the nephron, even though each is operating on a progressively small tubular load. However, none of the mechanisms, in isolation, is sufficient to explain salt balance over the range of voluntary intake. Combination of factors demonstrates synergism rather than simple additivity, resulting in more than enough reserve capacity for salt excretion.