Early use of plasmapheresis for recurrent post-transplant FSGS

Recurrence of focal segmental glomerulosclerosis (FSGS) in an allograft is a challenging clinical situation because it frequently results in graft loss. We report our experience with early use of plasmapheresis in recurrent FSGS. Of the 18 (33%) children with biopsy-proven FSGS (in their native kidneys) transplanted at our institution, 6 had recurrence (elevated urine protein/creatinine ratios) post transplant and were treated with plasmapheresis. Patients who received treatment within 1 day of the recurrence (4/6) went into remission after 5–13 plasmapheresis treatments, within 5–27 days of starting treatment. Patients who did not respond to plasmapheresis (2/6) were treated 7 and 17 days after onset of proteinuria; 1 of these had acute tubular necrosis and acute rejection leading to graft loss and the other developed acute rejections, ongoing proteinuria, and subsequent graft loss. All 4 patients who went into remission have maintained good graft function, 22–53 months post transplant. In our experience early institution of plasmapheresis for recurrent post-transplant proteinuria in FSGS is effective.     

Complete remission of post-transplant FSGS recurrence by long-term plasmapheresis

Focal segmental glomerulosclerosis (FSGS) is known to recur in approximately 30% of renal allografts with graft loss in about half of these cases. The exact etiology remains unclear, though a putative circulating permeability factor or loss of inhibitory substances is being discussed. Different therapeutic approaches have been used. We report on a 10-year-old Arabian boy with a recurrence of FSGS immediately after transplantation. In addition to intensifying immunosuppressive therapy with high-dose cyclosporin A and cyclophosphamide, plasmapheresis was initiated and remission was achieved after 8 months. Three weeks after cessation of plasmapheresis a relapse occurred. Plasmapheresis was resumed and remission was achieved again after four additional sessions. The interval between plasmapheresis treatments was then gradually increased and fourteen months after transplantation plasmapheresis was stopped again. Since then (1.5 years after cessation of treatment) the patient has been in complete remission without any further episode of proteinuria. In conclusion, complete and sustained remission with stable renal function was achieved in our patient by long-term plasmapheresis in combination with intensified immunosuppression. Therefore, continuation of plasmapheresis treatment should be considered even in the situation of initial non-response.     

马蹄肾合并肾小球病的临床病理分析

也页目的：马蹄肾是先天性肾脏融合畸形,马蹄肾合并肾小球病时,由于担心肾穿刺术后并发症,很少进行肾活检,从而得不到明确的病理诊断,难以得到应有的正确治疗。本文通过总结分析马蹄肾合并肾小球病的临床病理资料,旨在提高其诊断与治疗水平。方法：收集2008年1月~2013年6月在解放军总医院就诊,通过影像学确诊马蹄肾且肾活检病理诊断为肾小球病的病例。回顾分析这些病例的临床资料、实验室检查、影像学检查、肾活检适应证的把握、肾穿刺注意事项、肾活检病理检查结果以及治疗随访的资料。结果：共5例患者影像学检查确诊马蹄肾且肾活检病理诊断为肾小球病。（1）临床上主要表现为夜尿增多、下肢水肿、高血压及尿检异常。（2）尿蛋白定量均〉1 g/24 h,血肌酐正常或偏高。（3）影像检查明确诊断为马蹄肾,均为下极融合。（4）均有肾活检的适应证,没有肾脏大血管畸形等禁忌证,患者血压均控制在140/90 mmHg以下,凝血功能正常;在患者签署知情同意书后,由经验丰富的医生在超声引导下用肾穿刺活检枪在“肾上极”进行肾活检;肾穿刺术后严密观察,患者没有出现术后并发症。（5）肾活检病理诊断分别为局灶节段性肾小球硬化、膜性肾病、原发性IgA肾病、过敏性紫癜肾炎（继发性IgA肾病）、狼疮肾炎。（6）根据肾活检病理结果给予相应的治疗,每月随访1次,随访6个月后结果显示患者尿蛋白定量明显下降、血压及血肌酐趋于稳定。结论：肾小球病是马蹄肾的重要合并症,充分评估其肾活检的意义及风险,明确其病理类型,有助于指导治疗、延缓疾病的进展。     

Management of extreme azotemia from urinary tract obstruction without dialysis. Clinical correlates and kinetic modeling of the recovery of renal function

The recovery of renal function following release of urinary tract obstruction with advanced azotemia determines both the need for emergency dialysis in the early post-obstructive period and the long-term planning for chronic kidney disease management. A man with prostatic cancer who presented with 16 days of anuria and a serum creatinine (Scr) of 42.7 mg/dl but had evidence suggesting residual renal function was managed conservatively and reached a steady-state Scr of 1.6 mg/dl within 84 h of urinary bladder catheterization. Modeling of the decrease in Scr taking into account the decline in the body creatinine pool that existed prior to the release of the obstruction and the accumulation in body fluids of creatinine produced after the release of the obstruction suggested that recovery of the value of glomerular filtration rate corresponding to the steady-state Scr occurred at the release of the urinary obstruction. The case illustrates both the clinical factors that may lead to the decision to postpone dialysis in a patient presenting with extreme obstructive azotemia and a novel method of modeling the recovery of renal function after release of the obstruction.     

骁悉(MMF)预防肾移植术后急性排斥的临床观察

应用新型免疫抑制剂MMF预防肾移植术后急性排斥进行随机对照临床观察。MMF应用组11例,对照组10例。随访十二个月以上,排斥均有病理证实。结果提示;MMF组发生急性排斥仅占9％(1/11),经小剂量激素冲击逆转。对照组发生急性排斥占30％(3/10),2例为难治性排斥,经大剂量激素、OKT_3治疗无效后改用MMF,急性排斥逆转,肾功能恢复正常,1例细胞性排斥经大剂量激素冲击治愈。对照组1例肝胰损害患者改用MMF后治愈。临床研究表明MMF具有预防和减少急性排斥发生的效果而且有抗难治性排斥的作用,还具有对CsA有严重并发症者的补救作用,MMF的安全性稳定。副作用主要是腹泻,减药可缓解。     

Pulse methylprednisolone treatment of idiopathic steroid-resistant nephrotic syndrome

Although much of the interest in pulse methylprednisolone therapy (PMT) has centered around its use in children with focal segmental glomerulosclerosis, PMT has also been shown to be effective in the treatment of other proteinuric renal diseases. We hypothesized that a PMT-based treatment protocol, derived from the Tune-Mendoza protocol, would effectively induce a more rapid remission in young children with idiopathic steroid-resistant nephrotic syndrome (SRNS). A retrospective analysis was conducted of 11 consecutive SRNS patients (mean age 3.6±1.5 years) that received PMT between 1 August 1992 and 1 May 1998. The initial mean urinary protein/urinary creatinine ratio (UP/UC, mg/mg) was 8.3±9.7 and mean estimated creatinine clearance (C _Cr) 137.7±47.0 ml/min per 1.73 m². An average of 24.8±10.5 PMT doses were given. The mean duration of PMT therapy until remission was 23.4±29.9 days (median 12 days). Cyclosporine and cyclophosphamide were used to maintain and extend remissions in 5 and 4 patients, respectively. At the conclusion of the study, the mean UP/UC was 0.12±0.22 and mean C _Cr 151.8± 39.8 ml/min per 1.73 m² (no C _Cr≤100 ml/min per 1.73 m²). Of the 11 patients, 9 attained complete remission. Adverse effects were mild and infrequent. This PMT protocol appears to safely and effectively induce remission in young children with SRNS. A future prospective trial that evaluates the efficacy of PMT in young children with SRNS is warranted. Received: 15 March 2000 / Revised: 14 August 2000 / Accepted: 18 August 2000     

晨尿蛋白/尿肌酐比值评估CKD患者尿蛋白排泄临床应用评价

目的 探讨晨尿蛋白/尿肌酐比值评估CKD患者尿蛋白排泄的临床价值.方法 选取住院慢性肾脏病患者136例,检测晨尿蛋白/尿肌酐和24h尿蛋白定量并进行相关性分析;分析GFR、性别、年龄、体重指数对二者相关性的影响,绘制ROC曲线分析确定晨尿蛋白/尿肌酐比值相对于24h尿蛋白定量≥0.15g,24h尿蛋白定量≥1.00g和24h尿蛋白定量≥3.00g的最佳诊断点.结果 晨尿蛋白/尿肌酐比值与24h尿蛋白定量呈显著正相关(r=0.83;P ＜0.001);GFR、性别、年龄、体重指数对二者的相关性没有影响;24h尿蛋白定量≥0.15g,24h尿蛋白定量≥1.00g和24h尿蛋白定量≥3.00g时,临床诊断敏感性和特异性最佳点分别为晨尿蛋白/尿肌酐比值≥0.20g/gcr,晨尿蛋白/尿肌酐比值≥0.95 g/gcr和晨尿蛋白/尿肌酐比值≥2.92g/gcr.结论 晨尿蛋白/尿肌酐比值可替代24h尿蛋白定量,监测肾脏病患者尿蛋白排泄情况.     

Completely reversed acute rejection is not a significant risk factor for the development of chronic rejection in renal allograft recipients

Although acute rejection (AR) has been shown to correlate with decreased long-term renal allograft survival, we have noted AR in recipients who subsequently had stable function for more than 5 years. We reviewed 109 renal graft recipients with a minimum of 1 year graft survival and follow-up of 5–8 years. Post-transplant sodium iothalamate clearances (IoCl) measured at 3 months and yearly thereafter were used to separate recipients into 2 groups. In 61 patients (stable group), there was no significant decrease ( > 20 % reduction in IoCl over 2 consecutive years) in IoCl. Forty-eight patients had significant declines in IoCl (decline group). Groups were compared for incidence, severity, timing, and completeness of reversal of AR. Rejection was considered completely reversed if the post-AR serum creatinine (Scr) returned to or below the pre-AR nadir Scr after antirejection therapy. The incidence of AR was not significantly different between groups (47 % vs 52 %). A trend toward a lower mean number of AR episodes per patient was noted in the stable group (0.69 vs 1.04, P = 0.096), but the timing of AR was not different. Steroid-resistant AR occurred in approximately 25 % of both groups. A striking difference was seen in complete reversal of AR, with the stable group having 100 % (42/42 episodes of AR in 29 patients) complete reversal whereas only 32 % (8/25) of the patients in the decline group had complete reversal (P < < 0.001). Of 8 declining patients with complete reversal, graft loss was due to chronic rejection (CR) in only 3. Seventeen declining patients had incomplete reversal of AR, and 82 % (14/17) lost their grafts to CR. Overall, only 8 % (3/37) of the recipients with complete reversal of AR developed CR. No patients with incompletely reversed AR had stable long-term function as measured by IoCl. AR is not invariably deleterious to long-term renal graft function if each episode of AR can be completely reversed. Received: 9 March 1999/Revised: 28 December 2000/Accepted: 11 April 2000     

Renal biopsy in children with asymptomatic hematuria or proteinuria: survey of pediatric nephrologists

The decision to perform a renal biopsy on children with asymptomatic hematuria or proteinuria remains a problem for clinicians. To assess the current opinion of 349 pediatric nephrologists on this issue, case summaries of a 9-year-old boy with 20 urinary red blood cells per high power field without proteinuria and a 9-year-old boy with 2+ proteinuria (600 mg/day) without hematuria were distributed to each specialist. Seventy-three percent (n=256; 31, male:female) responded. Five percent would biopsy the child with asymptomatic hematuria. The main reasons were academic interest, parental pressure for a diagnosis/prognosis and concern for future economic impact on the child (i.e., life insurance). The determinations to biopsy for hematuria were not related to age or sex of the nephrologist. In contrast, 38% (n=96) of the pediatric nephrologists would perform a biopsy on the child with proteinuria. The major reasons for biopsy were academic interest and potential for drug therapy. With a normal history, physical examination and laboratory/radiographic evaluation, the vast majority of pediatric nephrologists in North America support a conservative approach to the child with asymptomatic hematuria or proteinuria.     

Renal functional reserve in children with a previous episode of haemolytic-uraemic syndrome

Renal function [creatinine clearance (C _Cr)] and renal functional reserve (RFR) was measured in 16 children who had had haemolytic-uraemic syndrome (HUS) an average of 6.6±0.72 years previously. All patients had normal plasma creatinine and blood pressure and only 3 had proteinuria, which was mild in every instance. Patients were studied whilst ingesting three diets which provided an average of 1.5, 2.1 and 3.1 g protein/kg body weight per day, respectively. Diets were administered over three consecutive periods of 7 days each andC _Cr was measured on the 7th day of each diet. Values tended to correlate with protein intake. They were in the normal range when patients were taking 1.5 and 2.1 g protein diets and increased markedly in 13 of the 16 patients (P<0.001) when they ingested the high-protein diet (3.1 g). The effect on glomerular filtration rate (GFR)-measured byC _Cr and inulin clearance (C _in)-of an acute oral protein load was studied in 12 of the HUS patients and four control subjects. In the control periods, prior to the protein load, values forC _Cr were similar in the HUS and control subjects (104.0±11.0 vs 121.6±10.1 ml/min per 1.73 m², NS). HoweverC _in values were significantly reduced in HUS patients (59.5±9.2 vs 102.7±12.4 ml/min per 1.73 m², (P<0.025). TheC _Cr/C _in ratio in the patients averaged 2.10 compared with 1.13 in controls. Acute protein loading was accompanied by an increase inC _in in all controls but in only 8 of the 12 patients. Baseline values forC _in did not correlate with the presence or absence of protein-stimulated enhancement ofC _in. TheC _Cr/C _in ratios after protein loading remained twice as high in HUS patients as in controls. The data indicate thatC _Cr is not an accurate indicator of GFR in children who have had acute renal injury. Tubular secretion of creatinine represents a greater proportion of excreted creatinine in these children, may maintain serum creatinine in the normal range and mask the decrease in GFR. The study also emphasizes the problems of measuring RFR in these children.     

血清及尿白细胞介素-6检测在肾移植中的意义

目的探讨血、尿ＩＬ－６检测在肾移植急性排斥（ＡＲ）诊断及鉴别诊断中的作用。方法应用ＥＬＩＳＡ技术，分别对肾移植术后不同状态下患者血、尿ＩＬ－６水平进行检测。结果急性排斥及感染患者血ＩＬ－６水平较环孢素（ＣｓＡ）中毒、急性肾小管坏死（ＡＴＮ）、移植肾功能正常及正常对照组高。尿ＩＬ－６在急性排斥及感染组也较ＣｓＡ中毒、ＡＴＮ、移植肾功能正常组有明显升高，而急性排斥组较感染组升高更明显。结论血、尿ＩＬ－６水平的升高可作为判断肾移植急性排斥的指标之一；也可作为鉴别急性排斥反应与ＣｓＡ中毒、ＡＴＮ的重要参考指标；对鉴别急性排斥反应和感染具一定的参考价值     

Plasmapheresis treatment for recurrent focal sclerosis in pediatric renal allografts

Recurrence of focal segmental glomerulosclerosis (FSGS) in pediatric renal allografts is associated with a poor graft survival. This study reports on plasmapheresis for the treatment of recurrent FSGS in pediatric renal transplant recipients. The records of 100 consecutive pediatric (age <21 years) renal transplants were reviewed. Twenty patients had FSGS as the cause of renal failure. Eight of these (40%) had a recurrence (protein-uria >1 g/m² per day) within 1 month of transplantation. Five of six patients treated with plasmapheresis went into remission (<0.2 g/m² per day), receiving a total of 42±26 (12–73) sessions, with the mean number of sessions required to achieve a remission being 24±17 (8–51). One patient had a second recurrence 1 year following cessation of plasmapheresis and responded to another course of plasmapheresis. The 1 patient who did not respond to plasmapheresis had a delay in initiation of therapy of 42 days. Plasmapheresis initiated within 48 h of recurrence resulted in earlier remissions and improved graft survival among our patients. Plasmapheresis appears to be effective in treating recurrent FSGS following kidney transplantation and should be started as soon as possible. The number of plasmapheresis sessions used to achieve remission should be adjusted according to response rather than adhering to a fixed protocol. Received: 22 November 1999 / Revised: 2 March 2000 / Accepted: 6 March 2000     

Comparison of different equations for estimated glomerular filtration rate in patients with chronic kidney disease

Objective To compare different equations for estimated glomerular filtration rate (eGFR) in patients with chronic kidney disease (CKD). Methods Hospitalized patients with CKD from the nephrology department of the First Affiliated Hospital of Nanjing Medical University (Jiangsu Province Hospital) were recruited between December 2014 and May 2015. The calculations of eGFR and 24 h creatinine clearance rate (Ccr) were accomplished in three days after admission. The eGFRs were calculated separately using the 24 h creatinine clearance rate adjusted by the standard body surface area (Ccr_BSA), Cockcroft-Gault equation adjusted by the standard body surface area (eCcr_BSA), CKD-EPI creatinine equation (EPI_Cr), CKD-EPI cystatin C equation (EPI_CysC), CKD-EPI creatinine-cystatin C equation (EPI_Cr_CysC), simplified MDRD (MDRD) and China MDRD equations. The EPI_Cr_CysC equation was used as the standard and the precision and accuracy of the other six equations were compared and analyzed. Results A total of 403 CKD participants were enrolled in the study, with 228 male patients and a mean age of (54.9±18.4) years. The main primary diseases were chronic glomerulonephritis (43.7%) and diabetic nephropathy (13.2%). The median concentration of serum creatinine and cystatin C were 117.5 (69.7, 242.4) μmol/L and 1.80 (1.13, 3.31) mg/L, respectively. The median values of Ccr_BSA, eCcr_BSA, MDRD, China MDRD, EPI_Cr, EPI_CysC and EPI_Cr_CysC equations were 50.8 (21.1, 96.2), 51.9 (23.3, 93.2), 53.6 (23.0, 97.4), 52.2 (22.4, 94.1), 53.2 (22.1, 97.3), 35.1 (15.4, 67.0) and 49.1 (22.8, 82.3) ml?min-1?(1.73 m2)-1, respectively. There was well agreement among MDRD, China MDRD and EPI_Cr equations, while there were large differences between equations derived from CysC (EPI_Cr_CysC and EPI_CysC) and equations derived only from creatinine (EPI_Cr, MDRD, China MDRD, eCcr_BSA, Ccr_BSA equations). Compared with EPI_Cr_CysC equation (the reference equation), EPI_Cr equation showed the highest accuracy [percentage of other eGFR equation calculations that were ＞30% of the reference equation calculations (1-P30), 30.8%] while Ccr_BSA equation showed the lowest (1-P30, 42.4%). EPI_CysC equation showed the highest precision [inter-quartile range (IQR) of the difference, 11.7 ml?min-1?(1.73 m2)-1] while Ccr_BSA equation showed the lowest [IQR of the difference, 22.8 ml?min-1?(1.73 m2)-1]. Conclusions The agreement among equations derived only from creatinine is better; while it exhibits some differences between equations with cystatin C and equations derived only from creatinine. The accuracy of EPI_Cr equation is second only to EPI_Cr_CysC equation and it is currently the most suitable eGFR equation for clinical popularization of renal glomerular function assessment.     

葛根素对急性胆源性胰腺炎肾损害内皮素机制的干预

目的 探讨急性胆源性胰腺炎肾损害的内皮素机制,并观察中药葛根素对其的改善作用. 方法 选择急性胆源性胰腺炎伴肾功能损害的患者32例,随机分为术后加用葛根素组(A组)和术后常规处理组(B组),各16例.另选同期急性胆源性胰腺炎不伴有肾功能损害的患者16例为C组,选无胆源性胰腺炎的普通肝胆疾病患者16例为D组.观察术前及术后1周各组血清内皮素及肾功能指标内生肌酐清除率的变化. 结果 术前A、B、C三组ET值均高于D组(P＜0.001),A、B两组内皮素值均高于C组(P＜0.001).术后1周,A组内皮素值低于B组(P=0.014),A组Ccr值高于B组(P=0.002). 结论 内皮素缩血管、引起肾血流下降的作用是急性胆源性胰腺炎时肾脏功能损害的重要机制.葛根素可以降低急性胆源性胰腺炎肾损害患者的血清内皮素含量,提高Ccr值对急性胆源性胰腺炎肾损害有一定的改善作用.     

Differential risk of remission and ESRD in childhood FSGS

Focal segmental glomerulosclerosis (FSGS) is the leading cause of steroid-resistant nephrotic syndrome in childhood and the most common form of end stage renal disease (ESRD) from glomerular disease. In order to assess the risk of progression of children with primary FSGS and the impact of proteinuria remission status on disease progression, we undertook this study to describe a cohort of 60 children and adolescents from the Glomerular Disease Collaborative Network. Of the 60 patients included in the cohort, 58% were African American. Median age was 16 years. Proteinuria ranged from 1.0–24.0 g/day/1.73 m²; 57% were hypertensive, and the median estimated glomerular filtration rate (eGFR) was 90.2 ml/min/1.73 m². Complete remission was achieved in 20%, partial remission in 33%, and 47% have not achieved remission during follow-up with all prescribed therapy. Only ACE-I/ARB therapy was predictive of proteinuria remission in multivariate analysis (hazard ratio [HR] 3.35; 95% confidence interval [CI] 1.42–7.92). Renal survival was much improved in patients with complete or partial remission compared with no remission in univariate analysis. In multivariate analysis comparing no remission status, complete remission was associated with a 90% decreased risk of ESRD (HR 0.10, 95% CI 0.01–0.79, p =0.03). In summary, proteinuria remission status is a valid predictor of long-term renal survival in children with FSGS.     

Acute renal failure in cardiothoracic surgery patients: what is the best definition of this common and potent predictor of increased morbidity and mortality

BACKGROUND: Universal agreement on criteria for acute renal failure (ARF) is lacking. The purpose of the current study was to determine which of 6 definitions for ARF best predicted clinical outcomes in postoperative cardiothoracic surgery (CTS) patients. METHODS: Criteria for ARF were retrospectively applied to 1,085 CTS patients. General linear models analyzed length of stay (LOS) and ventilator days with logistic regression for mortality. RESULTS: Thirty-seven percent of patients met at least 1 of 6 definitions of ARF. For each 1-mg/dL increase from the initial creatinine, LOS increased by 6.96 days, ventilator days increased by 3.58 days, and mortality increased by 2.23 times (P < .0001). CONCLUSIONS: One definition that best predicted ARF was not found. ARF was a significant independent predictor of increased mortality, LOS, and ventilator days. Even small increases in creatinine correlate with clinically significant worsening of expected outcomes.     

A case of acute humoral rejection in liver transplantation: successful treatment with plasmapheresis and mycophenolate mofetil

We present a case of a 23-year-old female who underwent orthotopic liver transplantation (OLTx) for biliary atresia, 22 years after a failed Kasai operation. Unusually, her postoperative course was complicated by severe acute humoral rejection. In this case report, we discuss her management as well as the role of plasmapheresis in treating allograft dysfunction secondary to acute humoral rejection in liver transplant patients.     

Randomised open clinical trial of conversion from mycophenolate mofetil to azathioprine in cadaveric renal transplantation

Abstract Mycophenolate mofetil (MMF) is a powerful immunosuppressive drug with established efficacy and safety. The search for a less expensive immunosuppressive protocol has led to an open randomised clinical trial of conversion from MMF to azathioprine (Aza). A total of 28 renal allograft recipients treated with prednisone, cyclosporine, and MMF was randomised into two groups: converted (early conversion) and control (late conversion). Conversion from MMF to Aza was conducted at the end of the 4th post‐transplant month in the converted group and after the 12th month in the control. During the 20‐month observation period, biopsy‐proven acute rejection occurred more frequently in the converted than in the control group, although the difference was not statistically significant. Early conversion from MMF to Aza increased the risk of subsequent rejection in those patients who underwent at least one episode of acute rejection prior to conversion.     

同种异体肾移植患者血清SIL－2R水平变化及其临床意义

作者采用双抗体夹心酶联免疫吸附法（ＥＬＩＳＡ）对２０例同种异体尸肾移植患者进行了８９例次可溶性白介素２受体（ＳＩＬ－２Ｒ）检查。结果表明：移植前明显高于正常对照组，Ｐ＜０．００１。移植后随着肾功能的恢复而接近正常，但仍轻度高于正常对照组，Ｐ＜０．０１。发生急性排斥反应时较稳定期明显升高，Ｐ＜０．００１，且其上升时间早于血肌酐上升２～７天。而发生环孢素Ａ肾中毒或急性肾小管坏死时，血清ＳＩＬ－２Ｒ水平则变化不明显，Ｐ＜０．０５。因此，ＳＩＬ－２Ｒ的测定可作为移植肾排斥反应诊断和鉴别诊断的重要非创伤性指标。