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Background: Chronic active antibody-mediated rejection is a major etiology of graft loss in renal transplant recipients. However, there is no consensus on the optimal treatment strategies., Methods: Computerized records from Taichung Veterans General Hospital were collected to identify renal transplant biopsies performed in the past 7 years with a diagnosis of chronic active antibody-mediated rejection. The patients were divided into two groups according to treatment strategy: Group 1 received aggressive treatment (double filtration plasmapheresis and one of the followings: rituximab, intravenous immunoglobulin, antithymogycte globulin, bortezomib, or methylprednisolone pulse therapy); and group 2 received supportive treatment., Results: From February 2009 to December 2017, a total of 82 patients with biopsy-proven chronic antibody mediated rejection were identified. Kaplan-Meier analysis of death-censored graft survival showed a worse survival in group 2 (P = 0.015 by log-rank test). Adverse event-free survival was lower in group 1, whereas patient survival was not significantly different. Proteinuria and supportive treatment were independent risk factors for graft loss in multivariate analysis., Conclusions: Aggressive treatment was associated with better graft outcome. However, higher incidence of adverse events merit personalized treatment, especially for those with higher risk of infection. Appropriate prophylactic antibiotics are recommended for patients undergoing aggressive treatment.

Background: Despite the development of biomarkers and noninvasive imaging tools, biopsy remains the only method for correctly diagnosing patients with unexplained hematuria, proteinuria and renal failure. Renal biopsy has been performed for several decades in Taiwan; however, a national data registry is still lacking until 2013., Methods: The Renal Biopsy Registry Committee was established within the Taiwan Society of Nephrology in January 2013. A biopsy registry format, including basic demographic data, baseline clinical features, laboratory data, and clinical and pathological diagnosis was developed. Approval from the local institutional review board was obtained in each participating medical center., Results: From January 2014 to September 2016, 1445 renal biopsies were identified from 17 medical centers. 53.8% cases were reported in men. After excluding renal transplantation, renal biopsies were commonly performed in patients with primary glomerulonephritis (48.1%), secondary glomerulonephritis (36.2%), followed by tubulointerstitial diseases (12.3%) and vascular nephropathy (3.4%). Among primary glomerulonephritis, IgA nephropathy (26.0%), focal segmental glomerulosclerosis (21.6%), and membranous nephropathy (20.6%) were most frequently diagnosed. Diabetic nephropathy (22.4%) and lupus nephritis (21.8%) were the most common among secondary glomerulonephritis. Patients with minimal change disease and membranous nephropathy had heavier proteinuria than those with focal segmental glomerulosclerosis and IgA nephropathy (P < 0.001). Patients with minimal change disease had higher serum IgM and IgE levels. The most common cause of nephrotic syndrome in primary glomerular disease was membranous nephropathy (28.8%), followed by minimal change disease (28.2%). IgA nephropathy was the leading cause of chronic nephritic syndrome, acute nephritic syndrome, and persistent hematuria. The incidence of primary glomerulonephritis was approximately 2.19 in 100,000/year., Conclusions: This is the first report of the National Renal Biopsy Registry in Taiwan. IgA nephropathy is the most common primary glomerulonephritis, while membranous nephropathy is the most common cause of nephrotic syndrome. Primary glomerulonephritis distribution in Taiwan is slightly different from that in other Asian countries.

Renal biopsy remains the golden standard diagnosis of renal function deterioration. The safety in native kidney biopsy is well defined. However, it is a different story in allograft kidney biopsy. We conduct this retrospective study to clarify the safety of allograft kidney biopsy with indication.All variables were grouped by the year of biopsy and they were compared by Mann-Whitney U test (for continuous variables) or Chi-square test (for categorical variables). We collected possible factors associated with complications, including age, gender, body weight, renal function, cause of uremia, status of coagulation, hepatitis, size of needle, and immunosuppressants.We recruited all renal transplant recipients undergoing allograft biopsy between January of 2009 and December of 2014. This is the largest database for allograft kidney biopsy with indication. Of all the 269 biopsies, there was no difference in occurrence among the total 14 complications (5.2%) over these 6 years. There were only 3 cases of hematomas (1.11%), 6 gross hematuria (2.23%), 1 hydronephrosis (0.37%), and 2 hemoglobin decline (0.74%). The outcome of this cohort is the best compared to all other studies, and it is even better than the allograft protocol kidney biopsy. Among all possible factors, patients with pathological report containing "medullary tissue only" were susceptible to complications (P < 0.001, 1.8 of relative risk).In modern era, this study demonstrates the safety of allograft kidney biopsy with indication. Identifying the renal capsule before biopsy to avoid puncture into medulla is the most important element to prevent complications.

RANTES (Regulated on activation, normal T-cell expressed and secreted), recruits circulating leukocytes and augments inflammatory responses in many clinical conditions. Inflammatory responses in ischemia-reperfusion injury (IRI) significantly affect the unfavorable outcomes of acute kidney injury (AKI), and that infiltrating immune cells are important mediators of AKI. However, the significance of RANTES in AKI and whether hypoxia-induced LncRNAs are involved in the regulatory process of AKI are not known. Here we show that, in the kidney IRI mice model, significant RANTES expression was observed in renal tubular cells of wild type mice. RANTES deficient (RANTES(-/-)) mice showed better renal function by reducing the acute tubular necrosis, serum creatinine levels, infiltration of inflammatory cells and cytokine expressions compared to wild type. In vitro, we found that RANTES expression was regulated by NF-κB. Further, renal tubular cells showed deregulated LncRNA expression under hypoxia. Among HIF-1α dependent LncRNAs, PRINS (Psoriasis susceptibility-related RNA Gene Induced by Stress) was significantly up regulated in hypoxic conditions and had specific interaction with RANTES as confirmed through reporter assay. These observations show first evidence for RANTES produced by renal tubular cells act as a key chemokine in AKI and HIF-1α regulated LncRNA-PRINS might be involved in RANTES production.

Objectives: High terminal serum creatinine level in a deceased donor has been reported as the second most frequent cause of refusal for kidney transplantation. A growing body of evidence has shown a comparable outcome of kidney transplantation from deceased donors with acute kidney injury (AKI). However, the influence of the severity of AKI on graft outcomes remains to be elucidated., Methods: In this retrospective cohort study, 84 consecutive kidney transplants from 57 standard-criteria donors were classified into 4 groups by RIFLE (Risk, Injury, Failure, Loss of function, and End-stage renal disease) classification according to donor AKI severity before kidney procurement. The donor and recipient characteristics and graft outcomes were compared., Results: Of 84 kidney transplants, 56, 11, 10, and 7 recipients were in the Non-AKI, Risk, Injury, and Failure groups. The mean terminal creatinine was 1.1, 1.6, 2.3, and 4.4 mg/dL in these 4 groups. However, the graft outcomes, including primary nonfunction rate, delayed graft function rate, acute rejection rate, renal function, graft survival and overall survival over the first 5 years had no statistical difference. A trend toward increasing delayed graft function rate as the severity of AKI increased was observed (Non-AKI, Risk, Injury, and Failure: 26.8%, 36.4%, 60.0%, and 57.1%, P = .099)., Conclusions: Our study demonstrates that AKI before procurement does not cause adverse long-term graft outcomes. Standard-criteria donors with AKI are suitable for kidney transplantation, even with a high severity of AKI., (Copyright © 2014 Elsevier Inc. All rights reserved.)

Background Doubling of serum creatinine (DSC) in transplantation has been seen as the end-point of renal function without pathological evidence. We conducted this study to elucidate the relationship between DSC and pathological findings. Material and Methods We conducted a retrospective cohort study to illustrate pathologic changes in patients receiving a kidney biopsy in the previous 5 years with clinicopathological correlations to DSC and proteinuria. Results Of a total of 99 kidney recipients (146 biopsies), results of graft biopsy were as follows: calcineurin inhibitor toxicity (CNI) (38.7%) and rejection (36.9%). Compared to males, females had higher proportions of class I (p=0.003) and class II PRA (p<0.001), and a higher rejection rate (p=0.042), but had the same clinical outcomes as males, like eGFR at follow-up (p=0.882), DSC (p=0.703), and proteinuria (p=0.745).                         Pathological diagnoses and findings were related to proteinuria: glomerulopathy (HR=4.9, p=0.01), AMR (HR=2.5, p=0.025), especially acute AMR (HR=2.9, p=0.008), chronic glomerular change (HR=10.2, p=0.002), arteriolar hyaline (HR=2.3, p=0.026), and mesangial matrix change (HR=6.3, p=0.002).                         BK nephropathy and rejection were the only 2 risk factors. Pathological findings favoring AMR (PTC infiltration and glomerulitis) showed a greater risk of DSC compared with those favoring CMR (interstitial inflammation, intimal arteritis, and tubulitis). DSC was correlated with clinical manifestation (rejection) and provided strong pathological evidence. Conclusions There was more acute rejection and chronic pathological change in women, but outcomes were the same due to less activity of renin-angiotensin-aldosterone and hyperfiltration in females. DSC as an end-point of graft function can be used to identify recipients, especially AMR or mixed AMR and CMR. 1. All forms of support received by each author: None of the authors received support. 2. Any potential conflict of interest for each author: No conflict of interest for any of the authors.

Background: Multidetector computerized tomography (MDCT) is lesser invasive than conventional angiography and has the advantage of assessment of vessels and surrounding anatomic variants before laparoscopic nephrectomy., Methods: From May 2005 to March 2011, 62 consecutive living kidney donors of mean age 45.3 ± 12.7 years (range 24-70 y, male:female 26:36) underwent laparoscopic nephrectomy to paired recipients of mean age 44.8 ± 14.0 years (range 17-74 y, male:female 38:24). The clinical characteristics and laboratory data of donors and recipients were collected for analysis. Graft function as indicated by estimated glomerular filtration rate (eGFR) was obtained from the last stable visit of the donors and the best value displayed by the recipients., Results: There was no significant correlation between CT kidney volume and and eGFR. By univariate analysis, donor age was associated with worse graft function (-0.51 mL/min lower eGFR per 1 year of donor age; P < .0001). Female sex and higher effective renal plasma flow/body mass index ratio were associated with better graft function; conversely, body weight and BMI were associated with poor graft function upon univariate and multivariate analysis. An ERPF of <220 mL/min and a donor age >45 y showed significantly lower eGFR. There was no effect of CT kidney volume <100 mL., Conclusions: Our preliminary data suggest that CT kidney volume does not predict posttransplantation graft function, but MDCT is still important for analysis of anatomy before laparoscopic nephrectomy among living donors., (Copyright © 2012 Elsevier Inc. All rights reserved.)

Lupus nephritis constitutes the major cause of morbidity and mortality in SLE. The long-term outcome of renal transplantation in lupus patients remains controversial, and the recurrence of lupus activity is a major concern. This study aims to determine the long-term outcome of renal transplantation in Chinese lupus patients and the evolution of lupus activity. A total of 23 lupus patients undergoing renal transplantation were enrolled and compared with 94 matched controls. The overall patient and graft survival rates at 10 years post-transplant in lupus group were not different from the control group (95.2% and 57.7% vs. 90.7% and 66.3%). Recurrence of lupus nephritis in renal allograft and flare-ups of lupus activity were not observed in this study. The SLE group had less acute rejection than the control group (20.4% vs. 29.8%, P<0.05). The infection rate between the two groups was similar (39.1% vs. 51.1%, P=0.427), although SLE group had a significantly higher rate of developing avascular necrosis (17.4% vs. 2.1%, P=0.04). In conclusion, patient and graft survival rates and other major complications in Chinese lupus patients are comparable to non-lupus transplant recipients caused by other diseases. Chinese patients with SLE are suitable candidates for renal transplantation.

Unilateral ureteral obstruction (UUO) is a well-characterized hydronephrosis model exhibiting interstitial inflammatory-cell infiltration and tubular dilatation followed by tubulointerstitial fibrosis of the obstructed kidney. Our recent report indicates that rapamycin is effective for 50% of transplant recipients with chronic allograft nephropathy. In this study, we investigate the effect of rapamycin on UUO-induced renal fibrosis. UUO or sham-operated rats were randomly assigned to rapamycin or vehicle and were killed on days 7 and 14 after UUO or sham operation. Rapamycin decreased cross-sectional and gross-morphology changes in the obstructed kidney significantly. Rapamycin markedly blunted the increase in weight of the obstructed kidney, obstructed kidney length, and the obstructed/non-obstructed kidney weight ratio (by 74.6, 42.8, and 61.6% on day 14, respectively, all P<0.01). The scores for tubular dilatation, interstitial volume, interstitial collagen deposition, and alpha-smooth muscle actin (alpha-SMA) after UUO were significantly reduced by rapamycin. Rapamycin also decreased the number of infiltrative anti-ED1-positive cells and the gene expression of transforming growth factor (TGF)-beta1 (84.8 and 80.2% on day 7) after UUO (both P<0.01). By double immunostaining and Western analysis, rapamycin blocked the TGF-beta1-induced loss of E-cadherin expression and de novo increase of the expression of alpha-SMA in a dose-dependent manner. In conclusion, rapamycin significantly attenuated tubulointerstitial damage in a UUO-induced rat model of renal fibrosis, suggesting that rapamycin may have the potential to delay the progression of tubulointerstitial renal fibrosis.

The causes of renal failure are diverse. Among them, monoclonal gammopathy is one important but easily-missed cause in aged people. Monoclonal gammopathy may produce a large number of abnormal immunoglobulins and/or fragments and produce different kinds of deposition in tissues, including cast, crystal, fibril and granules. Cast nephropathy is considered the hallmark of the renal disease in patients with multiple myeloma. Crystaglobulinemia syndrome and crystal nephropathy, on the other hand, have been rarely reported. Herein, we report a case of multiple myeloma presented with irreversible renal failure. The biopsy showed massive crystal deposition in bone marrow and kidneys.

Background: Membranoproliferative glomerulonephritis (MPGN) is a relatively rare primary glomerulonephritis (GN). Its incidence has decreased progressively in the past two decades. To improve knowledge of this rare GN, a retrospective review of 22 patients during a 12-year period was undertaken., Methods: From November 1982 to December 1994, from a total 814 cases of primary GN, 22 patients with primary MPGN were diagnosed. Clinical data, medical records, renal pathology and outcome were reviewed., Results: Patients included 15 male and 7 females, aged from 11 to 67 years. The average follow-up period was 46.3 months, with a range of 1 to 140 months. Tissue was available for electromicroscopic study in 11 cases; of which 9 cases fulfilled morphologic criteria of Type I MPGN; the other 2 cases were Type II MPGN. The clinical presentations at diagnosis included nephrotic syndrome (86.4%), impaired renal function (63.6%), microhematuria (50%), gross hematuria (31.8%) and hypertension (50%). Low serum C3 was found in 40.9% cases, 44.4% in Type I and 50% in Type III MPGN. The positive rate of hepatitis B virus infection was 22.7% with 33.3% in Type I and none in Type III MPGN. All 22 patients received various combined antihypertensive agents, immunosuppressant, anticoagulant and antiplatelet agents at diagnosis, but 17 had progressive disease, 4 maintained normal renal function with proteinuria and only 1 had complete remission. Fifteen patients, including six Type I and no Type III MPGN, progressed to end-stage renal failure. Both patients with Type III MPGN maintained normal renal function and responded to treatment. The 5 and 10 year actuarial renal survival rates were 33.3% and 16.7% respectively. The median kidney survival time was 51.2 months., Conclusions: A majority of cases with MPGN presenting with impaired renal function (86.7%) and hypertension (85%) at diagnosis progressed to end-stage renal failure. Delayed diagnosis and poor compliance were possible reasons for compared with for worse prognosis previous reports. But two patients with Type III MPGN had favorable prognosis previously described. Treatments generally failed to halt disease progression. Since at least five cases (22.7%) maintained normal renal function after treatments, a course of immunosuppressant is probably indicated if there is no contraindication. Further study with a larger population is warranted to clarify this issue.

IgA nephropathy (IgA N) is the most common type of primary glomerulonephritis (GN) diagnosed in Taiwan. From February 1983 to May 1992, 194 patients with primary IgA N, representing 25.3% of the primary GN, were diagnosed by renal biopsy at this hospital. Clinicopathologic correlation was made in 175 cases of IgA N with adequate clinical and pathologic data including light-(LM), immunofluorescent (IF) and/or electron-(EM) microscopy. Modified classification of Meadow et al. was adopted for the histologic grading of glomerular lesions. Forty-nine biopsies (28.0%) showed Grade IV and V lesions (Grade IV, 10.9%; Grade V, 17.1%, respectively) in association with a high level of serum creatinine and a lower frequency of gross hematuria when compared with lesions of histologic Grades I to III. Patients with Grade V lesions revealed a high frequency of hypertension as compared with those with Grades I to IV. The frequencies of nephrotic range proteinuria in those with various grades of IgA N was not statistically significant in this study. One hundred and thirty patients were followed up for one to eight and half years or until end-stage renal disease (ESRD) developed (mean 3.9 years), excluding the biopsies done at ESRD or from the graft kidney. Forty-two patients (32.3%) had chronic renal insufficiency, of those 25 (19.2%) eventually developed ESRD. Seventy-five percent of the patients with histologic Grades IV and V showed progressive renal disease, while only 16% of patients with Grades I to III lesions revealed progressive disease, the latter indicating a more benign course (P < 0.0001).(ABSTRACT TRUNCATED AT 250 WORDS)