Acute tubulointerstitial nephritis occurring with 1-year lapse in identical twins

We report monozygotic female twins who developed acute tubulointerstitial nephritis, with identical histological features and similar clinical symptoms, 1 year apart. Both patients presented with acute renal failure; only one developed bilateral uveitis after the onset of the nephritis.     

BK virus subtype 1 infection associated with tubulointerstitial nephritis in a renal allograft recipient

The BK polyomavirus (BKV) infects most of the human population, but clinically relevant infections are usually limited to individuals who are in an immunosuppressed state. The significance of BKV infection was investigated in a 50-year-old man who underwent cadaveric kidney transplantation and was treated with tacrolimus, mycophenolate mofetil and prednisolone. By staining renal biopsy specimens with a monoclonal antibody against BK large T antigen, we were able to observe the relationship between the appearance of the BKV antigen and the extent of immunosuppression in this patient. We also determined that BKV belonged to genotype I by analysis of viral DNA from the patient's urine.     

Repeat renal biopsy in a girl with tubulointerstitial nephritis and uveitis syndrome

A Japanese girl aged 8 years who presented with a 2-month history of uveitis subsequently developed tubulointerstitial nephritis. A percutaneous renal biopsy revealed massive interstitial mononuclear cell infiltrates consisting of CD4-positive T cells. Despite administration of topical corticosteroids, the ocular symptoms persisted. Systemic corticosteroid therapy dramatically reduced the ocular symptoms and urinary β₂-microglobulin (β 2MG) concentration. However, reducing the prednisolone dosage induced recurrence of uveitis associated with increased levels of urinary β 2MG. The CD4-positive T cell infiltration persisted in the second renal biopsy performed 6 months after the first renal biopsy. These observations suggest that the interstitial cell infiltration persists for a relatively long time in a proportion of patients with tubulointerstitial nephritis and uveitis syndrome (TINU). Although the renal outcome of TINU has been reported to be favorable, prolonged interstitial cell infiltration may affect long-term renal outcome. Selected patients with TINU should be followed with close observation. Received: 7 February 2001 / Revised: 8 June 2001 / Accepted: 27 June 2001     

Repeat renal biopsy in children with severe idiopathic tubulointerstitial nephritis

Idiopathic (primary) tubulointerstitial nephritis (TIN) of childhood is relatively rare. Four children, two with concomitant uveitis, aged 8–14 years, with idiopathic TIN who underwent repeat renal biopsy were retrospectively evaluated. At presentation, all had a significant elevation of the urinary ₂-microglobulin/creatinine ratio (2MG ratio), ranging from 10,100 to 44,550, with increased histological indices of tubulointerstitial scores (TI scores) in excess of 6 points. Three of the children received prednisolone (PSL) therapy following diagnosis, while the remaining child received the therapy 30 months after the first renal biopsy. In the children that received prompt PSL therapy, a rapid decrease in urinary 2MG ratio was observed and the TI scores obtained at a mean interval of 16 months after the first biopsy decreased to less than 5, while preserving renal function. In the remaining child that received delayed PSL therapy, persistent elevations of urinary 2MG ratio and TI scores were observed. He subsequently progressed to chronic renal insufficiency. These clinical findings suggest that persistent elevations of urinary 2MG ratio and TI scores are indicators of progression of renal failure in TIN. For successful treatment, early therapeutic intervention should be deployed in selected patients with severe idiopathic TIN.     

Renal tubular dysgenesis and tubulointerstitial nephritis antigen in juvenile nephronophthisis

Aim: The relationship between abnormalities of tubular architecture and tubulointerstitial nephritis antigen (TIN‐ag) in juvenile nephronophthisis (J‐NPH) was evaluated. Methods: Sixteen J‐NPH patients were examined. Nephrocystin‐1, TIN‐ag, type IV collagen, Fas antigen and the C5b‐9 complement complex were stained by immunohistochemical methods. Results: Renal tubules of patients with J‐NPH showed morphological abnormalities of tubular basement membranes (TBM) and frequent apoptosis of tubular epithelial cells. Additionally, the C5b‐9 complement complex was deposited within the TBM in the absence of immunoglobulin deposition, suggesting complement‐dependent TBM injury. Localization of TIN‐ag in the TBM of J‐NPH patients disclosed a partial defect or discontinuity in 14 of the 16 patients, while type IV collagen immunoreactivity was relatively preserved. These findings suggest that tubulogenesis is disturbed during nephronogenesis in J‐NPH patients because of a defect in nephrocystin, an NPHP gene product. TBM defects induce further morphological abnormalities such as cystic dilation of tubules; as tubular function impairment advances, the incomplete tubules may be injured by C5b‐9 complement complexes, followed by apoptotic cell death. Conclusion: TIN‐ag, which is important in early nephrogenesis, lacks normal activity, and vulnerable and incomplete tubules with deficient TIN‐ag expression are formed. Removal of these defective tubules by apoptosis combined with the C5b‐9 complement complex could be the primary reason for progression to end‐stage renal disease in J‐NPH patients.     

树突状细胞DC-SIGN在免疫介导实验性肾炎肾小管间质损伤中的作用及抗P选择素功能域单抗的干预调节

目的 探讨树突状细胞（DC）表面特异的胞间黏附分子3捕获非整合素 （DC-SIGN）在免疫介导肾毒血清性肾炎（NTN）肾小管间质损伤中的作用,以及抗P选择素功能域单抗（PsL-EGFmAb）的干预调节。 方法 WKY大鼠随机分为正常对照组、模型组及 PsL-EGFmAb干预组。模型组注射预制的兔抗大鼠肾毒血清1 ml/kg;PsL-EGFmAb组在注射肾毒血清同时及注射后2 h,注入PsL-EGFmAb 2 mg/kg;正常对照组则注射等量生理盐水。随后于实验第4、7、14 天,分别观察大鼠肾功能及肾组织病理变化,并采用免疫荧光法检测肾组织DC-SIGN+DC分布;实时定量 PCR 检测P选择素、T细胞表达和分泌因子（RANTES）、肿瘤坏死因子?琢（TNF-?琢）、白细胞介素（IL）-10、干扰素（IFN）-?酌、IL-4的mRNA 表达;流式细胞仪检测肾脏分离DC表面主要组织相容性复合体Ⅱ（MHCⅡ）、DC-SIGN、CD80表达;细胞迁移试验及混合淋巴细胞反应（MLR）检测DC迁移与刺激 T 细胞的能力;ELISA法测定MLR上清中IFN-γ、IL-4含量。 结果 NTN大鼠第4 天起,未成熟DC-SIGN+ DC即以肾间质为主浸润并于14 d成熟,且迁移及刺激 T 细胞增殖能力增强,其肾内分布与新月体形成、肾小管间质损伤程度及肾功能改变呈正相关。此外,大鼠第4 天起肾内趋化因子及促炎因子RANTES、 TNF-?琢 mRNA表达持续上调,而抗炎因子IL-10 mRNA于第4 天明显增强随后呈下调趋势;至14 d时IFN-γ/IL-4 mRNA比值增高,与DC成熟状况呈正相关。经PsL-EGFmAb干预,伴随DC 表面 DC-SIGN 及相应共刺激分子CD80表达下降,DC成熟、迁移及刺激 T 细胞增殖能力受抑,肾内促炎因子下降而抗炎因子上调,Th1/Th2 偏移受到抑制。同时大鼠肾内新月体形成减少,肾小管间质损伤程度减轻,且肾功能改善。 结论 DC-SIGN介导了DC 肾间质浸润,并可能是局部免疫反应失衡以及肾小管间质病变的重要调控因素。PsL-EGFmAb在抑制DC 迁移的同时可通过靶向DC-SIGN调抑 DC成熟及功能,进而发挥防治效应。     

Acute interstitial nephritis and nephrogenic diabetes insipidus following treatment with sulfamethoxazole‐trimethoprim and temozolomide

We report a case of acute interstitial nephritis with associated nephrogenic diabetes insipidus in a patient treated with temozolomide and sulfamethoxazole‐trimethoprim for glioblastoma multiforme. Kidney biopsy demonstrated focal tubulointerstitial change with tubular dilatation, epithelial change and interstitial inflammation. The patient's kidney function improved with cessation of sulfamethoxazole‐trimethoprim and treatment with hydrochlorothiazide for nephrogenic diabetes insipidus. Recommencement of temozolomide did not result in further deterioration in kidney function. In this case report, we discuss the novel association between sulfamethoxazole‐trimethoprim‐induced acute interstitial nephritis and nephrogenic diabetes insipidus, and suggest possible mechanisms involved.     

Erythropoietin and its non‐erythropoietic derivative: Do they ameliorate renal tubulointerstitial injury in ureteral obstruction?

Objectives: Pleiotropic effects of recombinant human erythropoietin (EPO) have recently been discovered in many non‐renal animal models. The renoprotective effects of EPO and carbamylated‐erythropoietin (CEPO), a novel EPO which has a small stimulatory effect on hemoglobin, have never been explored in unilateral ureteral obstruction (UUO), a chronic tubulointerstitial (TI) disease model which is independent of systemic factors. Methods: In order to examine the effects of EPO and CEPO treatments on renal TI injury, 36 male Sprague‐Dawley rats, weighing 250–320 g, underwent: UUO without treatment (group 1, n = 12), UUO with EPO (groups 2, n = 12), and UUO with CEPO (group 3, n = 12). EPO and CEPO were injected subcutaneously at a dose of 5000 u/kg to each respective rat at 1 day pre‐UUO and at day 3, 7 and 10 post‐UUO. After days 3, 7, and 14 of UUO, TI injury, collagen, α‐smooth muscle actin (α‐SMA) positive cell, ED1‐positive cell, terminal deoxynucleotidyl transferase (TdT) mediated nick‐end labeling (TUNEL)‐positive cell, and transforming growth factor‐β1 (TGF‐β1) messenger ribonucleic acid (mRNA) were determined. Bcl‐2 expression was also assessed to verify the mechanism of apoptosis. Results: At day 14 UUO caused severe TI injury with a significant increase in collagen, α‐SMA, ED1‐positive cell, TUNEL‐positive cell, and TGF‐β1 mRNA expression. Administration of EPO and CEPO significantly attenuated TI injury, collagen, ED1‐positive cells, and TUNEL‐positive cells. Only CEPO‐treated rats had decreased α‐SMA positive cells and TGF‐β1 mRNA. The expression of Bcl‐2 was demonstrated only in EPO‐treated rats. The hematocrit levels in EPO‐treated rats were higher than the control and CEPO‐treated rats. Conclusions: EPO and CEPO can limit 14‐day UUO‐induced TI injury by reducing inflammation, interstitial fibrosis, and tubular apoptosis.     

Serial renal biopsies in three girls with tubulointerstitial nephritis and uveitis syndrome

Tubulointerstitial nephritis and uveitis (TINU) syndrome is considered to have a good prognosis even without any immunosuppressive therapy, although there is no histological evidence to support this. The objective of this study was to evaluate, retrospectively, serial renal biopsy findings in three girls with TINU syndrome who were treated with prednisolone. At presentation, all patients had significantly elevated urinary β₂-microglobulin levels (7583–19,313 μg/l) and high serum creatinine levels (0.93–1.3 mg/dl). The elevated β₂-MG and creatinine levels persisted for 1 month, and renal biopsies were performed to establish a definitive diagnosis. The initial biopsy specimens of all patients revealed marked interstitial enlargement consisting of infiltration of lymphocytes; there was also notable tubulitis and infiltration of eosinophils. All patients received prednisolone therapy following the diagnosis. A second renal biopsy was performed 9 months after the first biopsy for two of three patients, and 2 years later for the third patient. The biopsy specimens taken at 9 months still showed histological changes of acute inflammation; in contrast, that taken at 2 years showed a lower degree of acute inflammation, but scar formation was observed in some regions. Based on these results, we conclude that selected TINU syndrome patients require some immunosuppressive therapy.     

The neurosurgical wound and factors that can affect cosmetic,functional, and neurological outcomes

Surgically accessing pathological lesions located within the central nervous system (CNS) frequently requires creating an incision in cosmetic regions of the head and neck. The biggest factors of surgical success typically tend to focus on the middle portion of the surgery, but a vast majority of surgical complications tend to happen towards the end of a case, during closure of the surgical site incisions. One of the most difficult complications for a surgeon to deal with is having to take a patient back to the operating room for wound breakdowns and, even worse, wound or CNS infections, which can negate all the positive outcomes from the surgery itself. In this paper, we discuss the underlying anatomy, pharmacological considerations, surgical techniques and nutritional needs necessary to help facilitate appropriate wound healing. A successful surgery begins with preoperative planning regarding the placement of the surgical incision, being cognizant of cosmetics, and the effects of possible adjuvant radiation therapy on healing incisions. We need to assess patient's medications and past medical history to make sure we can optimise conditions for proper wound reepithelialisation, such as minimizing the amount of steroids and certain antibiotics. Contrary to harmful medications, it is imperative to optimise nutritional intake with adequate supplementation and vitamin intake. The goals of this paper are to reinforce the mechanisms by which surgical wounds can fail, leading to postoperative complications, and to provide surgeons with the reminder and techniques that can help foster a more successful surgical outcome.     

Clinicopathological features and renal outcomes of IgA nephropathy with acute tubulointerstitial nephropathy

Objective To evaluate the clinicopathological characteristics and outcomes of IgA nephropathy (IgAN) with acute tubulointerstitial nephropathy (ATIN). Methods Patients who were diagnosed as IgAN with ATIN and IgAN without ATIN by renal biopsy in Peking University First Hospital were enrolled. There were 74 cases of IgAN with ATIN, and seventy-four cases of IgAN without ATIN were enrolled based on stratified sampling (chosen by 1∶1). The two groups were well matched with age, gender, follow-up time, mesangial hypercellularity(M), endocapillaryhypercellularity(E), segmental glomerulosclerosis(S), tubular atrophy/interstitial fibrosis(T) and cellular/fibrocellular crescent(C). The clinicopathological characteristics and outcomes of two groups were retrospectively analyzed. A composite end point, defined as 30% or 50% estimated glomerular filtration rate (eGFR) decline and end stage renal disease (ESRD) was used. Renal function and proteinuria during follow-up were observed. Renal survival was calculated by Kaplan-Meier survival analysis and risk factors of progression were analyzed by using univariate and multivariate Cox regression models. Results Seventy-four cases of IgAN with ATIN and seventy-four cases of IgAN without ATIN were enrolled. Serum creatinine [(185.6±83.2) μmol/L vs (146.3±69.2) μmol/L, P=0.010] and incidence of acute kidney disease (AKD) (31.1% vs 5.4%, P＜0.001) were higher in IgAN with ATIN group than those in IgAN without ATIN group. Patients in ATIN group received more immunosuppressive treatment (86.5% vs 58.1%, P＜0.001). During 1 year after biopsy, mean eGFR increased significantly in IgAN with ATIN group [(39.7±14.6) ml?min-1?(1.73 m2)-1 vs (47.2±19.9) ml?min-1?(1.73 m2)-1, P=0.017], but mean eGFR was not statistic different in IgAN without ATIN group [(60.0±30.5) ml?min-1?(1.73 m2)-1 vs (59.0±31.7) ml?min-1?(1.73 m2)-1, P=0.567]. Median follow-up was 23.0 months in IgAN with ATIN group, and Median follow-up was 30.0 months in IgAN without ATIN group. Incidence of composite end point had no significant differences between two groups. IgAN with ATIN was not the independent risk factor for end point. IgAN patients with ATIN were divided into two groups (with AKD and without AKD), then renal survival rate was higher (Log-rank test, χ2=5.293, P=0.021) and the risk for composite end point decreased by 79.2% (HR=0.208, 95%CI 0.046-0.939, P=0.041) in the group with AKD. Conclusions In IgAN, there is a subgroup of patients with the specific pathological phenotype combined with ATIN. Compared with those without AKD, the risk for composite end point of IgAN patients with ATIN and AKD showed a 79.2% decrease.     

The impact of reduced immunosuppression on graft outcomes in elderly renal transplant recipients

Abstract: Optimal immunosuppression (IS) for elderly kidney transplant recipients is unknown. We conducted a retrospective cohort study of recipients aged 60 yr or older to examine the impact of reduced IS on graft outcomes. Group 1 patients (n = 101) were initiated on mycophenolate mofetil 2 g/d and tacrolimus, target level 10–12 ng/mL; Group 2 patients (n = 88) with 1 g/d and 8–10 ng/mL, respectively. Dose adjustments were made as required. The groups were comparable except for diabetes, end‐stage renal disease duration, and induction. Mycophenolate mofetil dose was reduced in 62% and 38% of the patients, respectively (p < 0.01). Patients were followed for 23.8 ± 14.2 and 21.3 ± 11.8 months post‐transplant (p = 0.2). Twenty‐seven cases in Group 1 (26.7%) and eight in Group 2 (9.1%) lost their grafts (p = 0.01); 19 (18.8%) and 7 (8.0%) cases in each group because of death, respectively (p = 0.09). Sixteen patients in Group 1 (15.8%) and 18 in Group 2 (20.5%) experienced acute rejection (p = 0.36). Patients in Group 2 had a lower risk of graft loss compared with those in Group 1 [adjusted hazard ratio (HR): 0.27, p = 0.006, 95% CI: 0.11–0.69]. There were no significant differences between the groups regarding graft function, BK virus nephropathy, and CMV infection. Our results suggest that reduction in overall IS in this group was associated with improved graft and patient survival.     

A randomized exploratory trial of steroid avoidance in renal transplant patients treated with everolimus and low-dose cyclosporine.

BACKGROUND: Everolimus and cyclosporine exhibit synergistic immunosuppressive activity when given in combination. In this randomized trial, we explored whether the use of everolimus associated with low-dose cyclosporine could allow an early avoidance of steroids in de novo renal transplant recipients. METHODS: In this exploratory multicenter trial, 65 out of 133 patients treated with basiliximab (days 0 and 4), everolimus 3 mg/day and cyclosporine were randomized to stop steroids on the seventh post-transplant day (group A), whereas the remaining 68 continued low-dose steroid treatment (group B). RESULTS: During the follow-up, 30 patients of group A (46%) resumed steroids. According to the intention-to-treat analysis, the 3-year graft survival rate was 95% in group A and 87% in group B (P = ns). There were more biopsy-proven rejections in group A, the difference being of borderline significance (32% vs 18%; P = 0.059). After 3 years, mean creatinine clearance was 52.3 +/- 17.1 ml/min in group A and 52.2 +/- 21.5 ml/min in group B. It was similar in the group A patients who experienced rejection (49.8 +/- 14.7 ml/min) and those who did not (53.6 +/- 18.3 ml/min; P = 0.319). Mean serum cholesterol and triglyceride levels were, respectively, less than 250 mg/dl and less than 200 mg/dl in both groups, without any significant difference. Vascular thrombosis (0 vs 11.7%; P = 0.0043) was more frequent in group B. CONCLUSIONS: Treatment based on everolimus and low-dose cyclosporine allowed excellent renal graft survival and stable graft function at 3 years. An early discontinuation of steroids increased the risk of acute rejection, but was associated with a better graft survival in the long-term. However, it was well tolerated only by 54% of patients.     

Sunitinib‐related interstitial pneumonia after treatment with temsirolimus: A case of possible recall phenomenon

A 55‐year‐old Japanese man was admitted to Oita University Hospital (Oita, Japan) for pyrexia, malaise and dyspnea, and abnormal shadows on chest radiographs. He had started receiving sunitinib (37.5 mg a day for 3 weeks, followed by a 3‐week break before beginning the next dosing cycle) for metastatic renal cell carcinoma after the improvement of temsirolimus‐induced interstitial pneumonia. Sunitinib is a multiple tyrosine kinase receptor inhibitor approved for the treatment of metastatic renal cell carcinoma, and the most common clinical adverse effects of sunitinib are diarrhea, mucositis, stomatitis, hypertension, rashes and altered taste. We herein report a rare case of sunitinib‐related interstitial pneumonia after treatment with temsirolimus for metastatic renal cell carcinoma. This case suggests the possibility of recall phenomenon of drug‐induced pneumonia during the administration of additional chemotherapy.     

Demographics,management and treatment outcomes of benign and malignant retroperitoneal tumors in Japan

Objectives

To show the demographics, type of treatment and clinical outcomes of patients with retroperitoneal tumors in Japan.

Methods

We carried out a retrospective analysis of patients with retroperitoneal tumors treated between 2000 and 2012 at 12 university hospitals in Japan. Histology was re‐evaluated using the 2013 World Health Organization classification.

Results

A total of 167 patients were included in the analysis. The number of diagnosed patients increased over the 12‐year study period. Liposarcoma and schwannoma were the most common histological types among intermediate/malignant and benign tumors, respectively. The intermediate/malignant tumors were larger and were more frequently found in older people. Surgical resection was the primary treatment for 151 patients. The median survival duration for patients with malignant tumors was 91 months, and was significantly shorter than that for patients with benign and intermediate tumors (P < 0.01). R2 resection was associated with significantly shorter survival than R0/R1 resection for malignant tumors (P < 0.01), but not for intermediate. Grossly complete resection of the recurrent tumors improved survival.

Conclusion

The number of patients diagnosed with retroperitoneal tumors increased over time. R2 resection of primary tumors was found to be associated with poor prognosis in malignant tumors, but not in intermediate tumors. Complete surgical resection of recurrent tumors was associated with a better oncological outcome.     

Single graft loss in dual renal transplant recipients: impact of graft placement on recipient outcomes

We aimed to assess the impact of graft placement in dual renal transplantation on the risk for single graft loss and to report recipient outcomes. Between 2004 and 2007, 55 dual renal transplants were performed at our institution. Allografts were placed bilaterally (one in each iliac fossa) in 42 patients and unilaterally (both in the same iliac fossa) in 14 patients. Nine recipients (16.4%) underwent explantation of a single graft as a consequence of vascular thrombosis designated as the SINGLE group, whereas 46 had two functional allografts (DUAL group). There was a higher rate of graft loss in case of unilateral placement (n = 5/14) compared with bilateral placement (n = 4/41) (35.7% vs. 9.8%, P = 0.035). One‐year glomerular filtration rate was significantly lower in the SINGLE group (29.4 ml/min/1.73 m² vs. 49.4 ml/min/1.73 m² in the DUAL group, P < 0.05). Significantly, none of the nine recipients of the SINGLE group returned to dialysis with a mean follow‐up of 34.1 months. Graft survival at 1 year was 100% and 97.9% in SINGLE and DUAL groups, respectively. Unilateral placement of both allografts is associated with an increased risk of single graft loss and therefore lower renal function at 1 year. However, this strategy is safe in selected indications.     

In-vitro steroid sensitivity in patients with chronic uraemia and renal transplantation: possible association with HLA phenotypes

We studied in-vitro steroid sensitivity using the test of ADCCin 207 haemodialysed chronic uremic patients, 85 renal transplantpatients, and 75 healthy blood donors as normal controls. Theassociation of HLA phenotypes with the in-vitro steroid sensitivitywas assessed. The proportion of steroid-sensitive subjects wassignificantly higher in the normal control group than in thepatients. A significant association was observed between HLAB8 carriers and steroid resistance and between HLA DR6 carriersand steroid sensitivity.     

Effect of ABO blood type on the outcomes of patients with metastatic renal cell carcinoma treated with first-line tyrosine kinase inhibitors

Objectives

To assess the effect of blood type on survival outcomes and adverse events (AEs) in patients treated with tyrosine kinase inhibitors (TKIs) for metastatic renal cell carcinoma (mRCC).