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Introduction Recent studies have revealed the pivotal role of complement activation in the pathogenesis of antineutrophil cytoplasmic antibody–associated glomerulonephritis (ANCA-GN). This study investigated the clinicopathologic and prognostic significance of glomerular C3 deposition in the renal histopathology of patients with ANCA-GN. Methods We retrospectively identified 142 patients with ANCA-GN from 6 hospitals in Japan (2004–2020). C3 deposition was defined as C3 staining ≥1+ on a scale of 0 to 2+ using direct immunofluorescence (IF). The primary composite end points included a 30% reduction in estimated glomerular filtration rate (eGFR), end-stage kidney disease (ESKD), and death. We compared clinicopathologic features and long-term outcomes between patients with and without C3 deposition. Results C3 deposition was observed in 56 of 142 kidney biopsy samples (39.4%). Patients with C3 deposition had a lower serum C3 level (P = 0.002). During a median follow-up of 2.9 (interquartile range: 0.2–5.7) years, 69 events occurred and the cumulative event-free survival rate at 5 years was significantly lower in the C3-positive group than in the C3-negative group (log-rank: P = 0.002). In multivariable analysis, C3 deposition was significantly associated with the composite end points after adjusting for age, sex, baseline eGFR, serum C3 level, treatment, and the percentage of normal glomerulus, cellular crescents, global sclerosis, and interstitial damage (adjusted hazard ratio [HR] = 2.02, 95% confidence interval: 1.20–3.40, P = 0.008). Conclusion This study revealed that ANCA-GN patients with glomerular C3 deposition on IF had worse renal and overall survival rates., Graphical abstract

The aim of the study was to determine kidney survival and validate the novel international immunoglobulin A nephropathy (IgAN) prediction tool (PT) in the Latvian population. Adults with morphologically confirmed IgAN were included. Kidney survival was analysed with the Kaplan–Meier method. PT-assigned risk was compared with calculated risk by the Cox regression model. The Kaplan–Meier analysis included 95 patients. The five-year kidney survival Q3 was 24 months. Women had longer median kidney-survival time (> 60 months) than men (58 months). Median kidney survival in participants with MEST T0 was longer than 60 months; T1 and T2 were 40 and 18 months, respectively. Median kidney survival in participants with diastolic blood pressure (DBP) < 99 mmHg was longer than 60 months, whereas in patients with DBP 100–109 and 110 mmHg, it was 40 and 24 months, respectively. Cox regression analysis included 68 patients. A moderate degree of correlation was found between predicted and observed five-year risk (p = 0.001). Gender, tubular atrophy/interstitial fibrosis, DBP are significant factors affecting kidney survival. Since there was statistically significant correlation and reliability between PT and follow-up analysis data, we conclude that PT could be applied for use in the Latvian population.

Introduction: Clinical indicators or pathological features alone cannot reliably predict renal survival in patients with biopsy-confirmed diabetic nephropathy (DN). Therefore, this analysis sought to develop and validate a predictive model incorporating both clinical and pathological markers to predict renal outcomes in patients with biopsy-confirmed DN. Methods: A predictive nomogram was developed based upon data pertaining to 194 patients with biopsy-confirmed DN. The prognostic relevance of individual clinicopathological variables was assessed through univariate and multivariate Cox regression analyses. A prognostic nomogram was then developed and validated based upon concordance (C)-index values and calibration curves. Internal validation was conducted through bootstrap resampling, while the clinical utility of this model was assessed via a decision curve analysis (DCA) approach. Results: Nephrotic-range 24-h proteinuria, late-stage CKD, glomerular classification III–IV, and IFTA score 2–3 were all identified as independent predictors of poor renal outcomes in DN patients and were incorporated into our final nomogram. Calibration curves revealed good agreement between predicted and actual 3- and 5-year renal survival in DN patients with the C-index value for this nomogram at 0.845 (95% CI: 0.826–0.864). DCA revealed that our nomogram was superior to models based solely upon clinical indicators. Conclusion: A predictive nomogram incorporating clinical and pathological indicators was developed and validated for the prediction of renal survival outcomes in patients with biopsy-confirmed DN. This model will be of value to clinicians, as it can serve as an easy-to-use and reliable tool for physicians to guide patient management based on individualized risk.

Objectives: This study aims to assess the different predictors of renal and patient prognosis in anti-neutrophil cytoplasmic antibodies (ANCA)-associated vasculitis (AAV) patients with and without renal involvement. Patients and methods: A total of 79 patients (51 males, 28 females; mean age: 57.3±14.2 years; range, 18 to 71 years) with AAV between January 2006 and November 2019 were retrospectively analyzed. Demographic and laboratory data including the complement 3 (C3) serum levels and renal biopsy findings were extracted from the electronic and printed medical records of the hospital registry. Survival, renal survival, remission, and relapse outcomes were analyzed. Results: A total of 35% of the patients with renal involvement progressed to end-stage renal disease (ESRD). The dialysis requirement at the time of admission (hazard ratio [HR]: 21.95 [2.93-164.22]; p=0.003), estimated glomerular filtration rate (eGFR) (HR: 0.97 [0.94-0.99]; p=0.024) and Five-Factor Score (FFS) ≥2 at the time of diagnosis (HR: 3.59 [1.08-11.94]; p=0.037) were the predictors of ESRD. The five-year patient survival rate was 87.1%. The only predictor of mortality was age (HR: 1.07 [1.01-1.14]; p=0.024). The patients with hypocomplementemia (22%) had a lower remission rate (p=0.049), FFS ≥2 at the time of diagnosis (p=0.026), and higher levels of hematuria (p=0.004) and proteinuria (p=0.037). The FFS ≥2 at the time of diagnosis was an independent predictor of relapse (HR: 8.9 [1.02-77.36]; p=0.047). Conclusion: Our study suggests that the baseline renal function and FFS ≥2 at the time of diagnosis are the major prognostic factors for progression to ESRD in AAV patients. In addition, AAV patients with hypocomplementemia may have a lower remission rate.

Objective: To define predictors of response, time to response, flares, and long-term renal outcome in an inception cohort of proliferative lupus nephritis (PLN). Methods: We included 100 patients (80% female; mean age 31 ± 13 years) with biopsy-proven PLN (III, IV, III/IV + V). Clinical, laboratory, histological and therapeutical parameters were recorded at baseline, 6, 9, 12, 18, 24, 36, 72 months, time of flare, and last follow-up visit. Logistic and Cox-regression models were applied. Results: After induction treatment (69% received cyclophosphamide (CYC) and 27% mycophenolic acid (MPA)), partial (PR) or complete (CR) response was achieved in 59% (26% CR, 33% PR) and 67% (43% CR, 24% PR) of patients at 3 and 6 months, respectively; median time to PR was 3 months (IQR 5) and median time to CR was 6 months (IQR 9). Baseline proteinuria 0.8 g/day at 12 months was associated with a higher risk of flares (OR 4.12), while MPA and mixed classes with lower risk (OR 0.14 and OR 0.13, respectively). Baseline proteinuria >2 g/day and 12-month proteinuria >0.8 g/day correlated with a shorter time to flare (HR 2.56 and HR 2.57, respectively). At the end of follow-up, 10% developed stage 3–4 chronic kidney disease (CKD), and 12% end-stage renal disease (ESRD). Twelve-month proteinuria >0.8 g/day (OR 10.8) and interstitial fibrosis/tubular atrophy >25% (OR 7.7) predicted CKD or ESRD at last visit. Conclusions: Baseline proteinuria 0.8 g/day correlated with flares (ever) and time to flare and, along with baseline interstitial fibrosis/tubular atrophy >25%, predicted CKD or ESRD at the last visit.

The association between crescents and renal outcomes was inconsistent in a Chinese IgA nephropathy (IgAN) cohort, and limited research has investigated the prognosis of IgAN patients with crescents. Between January 2008 and January 2013, 169 consecutive IgAN patients with crescents in the Xijing Hospital, who were matched to IgAN patients without crescents at a 1:1 ratio by sex, age, eGFR, and proteinuria were reviewed. Combined events were defined by either a ≥ 50% reduction in eGFR or ESRD. All patients were followed for a mean of 49.9 ± 26.0 months, and 41 (12.1%) patients had developed combined events. Five multivariate Cox regression models were created, and crescents was an independent risk factor for combined events. In model 5, crescents (HR = 2.216, 95% CI 1.040–4.345, P = 0.039) were notably associated with the risk of combined events after adjusting for age, sex, smoking, TA-P, persistent hematuria, and TA-MAP. Of the IgAN patients with crescents, 17.2% had developed combined events. In the baseline variables model, age, proteinuria, eGFR, E1, T1–T2, and RAAS had statistically significant associations with combined events in the multivariate Cox regression analyses. In the time varying variables model, TA-P, persistent hematuria, and TA-MAP were independent risk factors for combined events. We validated that the presence of crescents was an independent predictor of combined events in Chinese IgAN patients. Age, proteinuria, eGFR, E1, T1–T2, RAAS, TA-P, persistent hematuria, and TA-MAP were independent risk factors for combined events in IgAN patients with crescents.

IntroductionLupus nephritis (LN) has a considerable impact on the morbidity and mortality of systemic lupus erythematosus (SLE) patients. Long-term comparative outcome data from the Indian subcontinent on treatment regimens with cyclophosphamide (CYP) and mycophenolate mofetil (MMF) are sparse. We assessed renal and patient survival for these patients in terms of the types of induction – CYP or MMF – and the two maintenance therapies – MMF or azathioprine (AZA).MethodsWe retrospectively analysed outcomes of 100 LN patients, 67 treated with CYP (26 class III, 25 class IV, 6 class III + V and 10 class IV + V; 40 Euro lupus regimen and 27 National Institutes of Health regimen) and 33 treated with a MMF-based regimen with steroids between July 2008 and June 2018. Data regarding demographic, clinical and histopathological features and the treatment given to all patients were extracted. Outcomes between the two regimens CYP and MMF were compared in terms of remission, dialysis and patient survival.ResultsThe clinical characteristics were similar in both groups, except that the activity index was higher in CYP patients (6.13 ± 4.48 vs. 4.61 ± 2.80). However, the chronicity index was similar. The overall remission rate was 70% at the end of induction. The rates of complete remission, partial remission and non-responders in the CYP group were 46.2%, 23.9% and 29.9%, respectively. However, in the MMF group, the corresponding rates were 57.6%, 12.1% and 30.3%, respectively. The 1-, 2-, 3-, 4-, 5- and 10-year patient survival rates in the CYP group were 89.5%, 86.2%, 86.2%, 83.8%, 83.8% and 83.8%, respectively. In the MMF induction group, the corresponding rates were 93.9%, 93.9%, 89%, 89%, 89% and 89%, respectively. At the end of the study, rates of end-stage renal disease in the MMF group and CYP group were 7.5% and 12.1%, respectively. The death-censored and non-censored renal survival rates were also similar in the long term. With regard to maintenance therapy, 3/56 (5.3%) in the MMF group and 7/34 (20.5%) in the AZA group experienced doubling of serum creatinine ( p = 0.03).ConclusionsLong-term outcomes in terms of patient and renal survival of LN patients treated with CYP and MMF induction are similar. Doubling of serum creatinine occurred more with AZA-based maintenance therapy than with MMF-based maintenance therapy. Most deaths occurred during induction, and sepsis was the most common cause of death.

The treatment options for systemic light chain amyloidosis (AL) are currently widening in an unprecedented way, brought about by an expanding arsenal of anti-myeloma therapy as well as by novel approaches to target toxic light chains and, most recently, deposited amyloid directly. In this context, accurate estimates of prognosis in AL, which allow for reliable patient advice and for example comparison of different therapies, are particularly important to clinicians. Some biomarkers and especially the genetic background of the underlying clonal disease as evaluated by interphase fluorescence in situ hybridization even have predictive value, enabling an appropriate treatment selection. Derived from the most frequently involved organs in AL, heart and kidney, this review focuses on overall survival and renal survival. A comprehensive overview and summary of reported prognostic factors and biomarkers in AL is given and the most important and validated factors are highlighted. Finally, established staging systems in AL as well as validated and perspective response criteria are presented.

Background Glomerular IgG deposition in patients with IgA nephropathy (IgAN) has been shown to be associated with poor renal survival; however, most published studies to date are too small-scale and inconsistent to provide guidance for clinical practice. Methods Based on renal biopsy findings, 742 patients were divided into the following groups: (i) IgA deposition alone (IgA) vs IgA + IgG deposition (IgA + IgG) and (ii) IgG co-deposition confined to the mesangium vs mesangium + capillary loops (CLs). The clinicopathological variables at biopsy and renal outcome were assessed. Results Of the 742 patients, 182 had IgG co-deposition and 51 had IgG deposits in the mesangium + CLs. Patients with IgG co-deposition were associated with severe clinical and pathological lesions, especially those with a location of IgG deposits in the mesangium +CLs. Kaplan–Meier analysis revealed that a lower renal cumulative survival rate was present in both patients with IgG co-deposition and those with a location of IgG deposits in the mesangium + CLs (all p

Background: The triglyceride–glucose (TyG) index is a simple, novel and reliable surrogate marker of insulin resistance. However, evidence for the prognostic impact of an elevated TyG index on IgA nephropathy (IgAN) is limited. Therefore, we evaluated the relationship between the TyG index and the risk of renal progression in IgAN. Method: This cohort study involved biopsy-proven IgAN between January 2009 and December 2018 in West China Hospital, in which patients were assigned to two groups based on the cut-off value of TyG using receiver operating characteristic (ROC) curves. A 1:1 matched-pair analysis was established to optimize the bias in IgAN by propensity score matching (PSM). The TyG index was calculated as ln [fasting triglyceride (mg/dL) × fasting glucose (mg/dL)/2]. The composite endpoint was defined by eGFR decreased ≥50% of the baseline level, end-stage kidney disease (ESKD), renal transplantation and/or death. Univariable and multivariable Cox proportional hazard models were applied to confirm the predictive value of the optimal marker. Results: Before PSM, a total of 1210 participants were ultimately included. During a median follow-up period of 55.8 months (range 37.20–79.09 months), 129 participants progressed to the composite endpoint (10.7%). After PSM, 366 patients were enrolled in the matched cohort, of whom 34 (9.3%) patients reached the endpoints. Based on the cut-off value of the TyG index, patients were divided into the low TyG index group (TyG ≤ 8.72, n = 690) and the high TyG index group (TyG > 8.72, n = 520). Further analysis demonstrated that a higher TyG index was significantly associated with a higher risk of reaching composite endpoints in IgAN patients in both the unmatched and matched cohorts (before PSM: HR 2.509, 95% CI 1.396–4.511, p = 0.002; after PSM: HR 2.654, 95% CI 1.299–5.423,p = 0.007). Conclusion: A high TyG index is associated with a higher risk of renal progression.

Interstitial fibrosis and tubular atrophy (IFTA) on a renal biopsy are strong indicators of disease chronicity and prognosis. Techniques that are typically used for IFTA grading remain manual, leading to variability among pathologists. Accurate IFTA estimation using computational techniques can reduce this variability and provide quantitative assessment by capturing the pathologic features. Using trichrome-stained whole slide images (WSIs) processed from human renal biopsies, we developed a deep learning (DL) framework that captured finer pathological structures at high resolution and overall context at the WSI-level to predict IFTA grade. WSIs (n=67) were obtained from The Ohio State University Wexner Medical Center (OSUWMC). Five nephropathologists independently reviewed them and provided fibrosis scores that were converted to IFTA grades: 50% (Severe). The model was developed by associating the WSIs with the IFTA grade determined by majority voting (reference estimate). Model performance was evaluated on WSIs (n=28) obtained from the Kidney Precision Medicine Project (KPMP). There was good agreement on the IFTA grading between the pathologists and the reference estimate (Kappa=0.622±0.071). The accuracy of the DL model was 71.8±5.3% on OSUWMC and 65.0±4.2% on KPMP datasets, respectively. Identification of salient image regions by combining microscopic and WSI-level pathological features yielded visual representations that were consistent with the pathologist-based IFTA grading. Our approach to analyzing microscopic- and WSI-level changes in renal biopsies attempts to mimic the pathologist and provides a regional and contextual estimation of IFTA. Such methods can assist clinicopathologic diagnosis.Translational statementPathologists rely on interstitial fibrosis and tubular atrophy (IFTA) to indicate chronicity in kidney biopsies and provide a prognostic indicator of renal survival. Although guidelines for evaluation of IFTA exist, there is variability in IFTA estimation among pathologists. In this work, digitized kidney biopsies were independently reviewed by five nephropathologists and majority voting on their ratings was used to determine the IFTA grade. Using this information, a deep learning model was developed that captured microscopic and holistic features on the digitized biopsies and accurately predicted the IFTA grade. The study illustrates that deep learning can be utilized effectively to perform IFTA grading, thus enhancing conventional clinicopathologic diagnosis.

Several studies have demonstrated the nephroprotective effects of estrogen on renal damage. In light of the inconsistent results of previous findings, this study aims to evaluate the in-depth role of menopausal hormone therapy (MHT) on the development of end stage renal disease (ESRD). 3,109,506 Korean adult women who had undergone a medical examination in 2009 (index year) were initially identified for inclusion in this study. We excluded subjects had not experienced menopause naturally, had data missing for at least one variable, and were diagnosed with ESRD within 1 year from the index year. MHT data was obtained from self-reporting questionnaires and the primary outcome was the development of ESRD from the index year until December 31, 2018. A final total of 1,460,311 subjects were included in this study. The participants were divided into four groups according to the duration of MHT; no history of MHT, MHT

Background and Aims Urinary Dickkopf-related protein-3 (DKK3), a stress-induced renal tubular glycoprotein, has been identified as a novel biomarker for chronic kidney disease patients at risk of kidney disease progression. The aim of our study was to assess urinary DKK3 as a diagnostic biomarker for predicting GFR loss and renal survival in a cohort of patients with ANCA-associated vasculitis Method We measured baseline urinary DKK3 levels in a cohort of patients diagnosed with ANCA-associated vasculitis (AAV), and repeated measurements at 1 and 3 months of diagnosis. Urinary DKK3 levels were normalized to urinary creatinine concentrations to account for dilution of the urine. The association between baseline uDKK3/creatinine levels and the rate of GFR loss was measured. The primary composite outcome was defined as an increase of >50% in baseline serum creatinine, initiation of renal replacement therapy or death. Results We included 36 AAV patients with a mean age 71.2 ±12.0 years, 55.6% males, with baseline eGFR at diagnosis 22.3 ±14.1 ml/min. There was a correlation between baseline DKK3-creatinine levels and age (r=0.48, p=0.003) and baseline eGFR (r=-0.327, p=0.051). Ten patients (27.8%) reached the primary composite outcome. Patients were then stratified into two groups according to baseline uDKK3 levels. The group of patients with baseline uDKK3-Creatinine >16000 pg/mg were older (76±12.5 vs 66.4 years, p=0.014), presented a lower baseline eGFR (16.2±10.8 vs 28.5±14.5 ml/min, p=0.007) and had higher baseline uCD163 levels (1135.1 [312.4-2537.5] vs 397.2 [146-809.4], p=0.089]). There were no differences in baseline proteinuria, microhematuria or histological class across the groups. After a median follow-up of three years, 44.4% of the patients in the highest DKK3 group reached the primary composite outcome, whereas only 11.1% of those with lower DKK3 levels reached the endpoint at the end of follow-up (p=0.026) . The area under the time-dependent curve for predicting the primary composite outcome according to uDKK3 was 0,677, with a sensibility of 80% and specificity of 61.5% at the cutoff 16056 pg/mg. Additionally, patients who had a >30% increase in uDKK3 levels after one month reached the primary composite outcome more often (40%) than those who remained with a stable or decreasing DKK3 levels (0%, p=0.04). There were no differences in the rate of change in DKK3 and the different treatment regimens. Conclusion Elevated urinary DKK3 levels help identify those patients who are at a higher risk of kidney disease progression and dialysis dependency over the next three years in ANCA-associated vasculitis. DKK3 monitoring could be considered in the follow-up of these patients to assess the effect of treatment and predict the long-term response.

Background and Aims Heat shock proteins(HSP) present an evolving role in immune response. ANCA associated vasculitis(AAV) is often associated with kidney injury and progression to chronic kidney disease(CKD) Method Twenty nine patients with biopsy proven renal AAV were followed(1995-2015). Study end point was renal death. Renal tissue at diagnosis was stained with monoclonal antibodies against HSP60 and HSP70. Interstitial inflammatory cells and interstitial fibrosis graded were evaluated as mild(0-50%) or severe(≥50%). Healthy renal tissue served as control. Survival analysis(Kaplan-Meier), Fisher’s exact test, or Test Chi-Square and bivariate analysis were performed. Statistical significance was set at Results Mean age and mean eGFR at baseline was 57,8±19.2 years and 24,47 ml/min/1,73m2 BSA respectively. Interstitial inflammatory infiltrates were present in most patients. Interstitial fibrosis was present in 10,3% of patients. Control biopsies showed a weak HSP expression. AAV-patients presented significantly higher HSP expression within crescents, proximal tubule, distal tubule and renal interstitium. Renal fibrosis associated with intense interstitial HSP70 expression(Pearson´s-R=0.521 p=0,004). Interstitial inflammatory infiltrates associated with increased distal tubular HSP60 expression(Pearson´s-R=0.672 p Conclusion Interstitial HSP70 overexpression is associated with worse renal outcomes in renal AAV. To our knowledge this is the first study that shows an association of renal heat shock protein expression and renal outcomes in an AAV cohort.

Background and Aims With increasing longevity, the numbers of elderly patients presenting with renal diseases including glomerular disease are increasing. Nephrotic syndrome (NS) is a common presentation of glomerular disease in the elderly. We performed this study to assess predictors of renal survival in this population. Method A retrospective study including one hundred and six patients aged 65 years or more hospitalized for NS in the Internal Medicine department A of Charles Nicolle hospital at Tunis, between January the 1st, 1975 and December the 31st, 2016. A multivariate study was carried out, the dependent variable being the evolution towards end-stage renal disease (ESRD). Results We studied 106 patients with an average age of 70 ± 4.5years [65-83 years] with a sex ratio (M/F) of 1.7. Twenty-three percent of patients were diabetic. The median proteinuria was 4.6 [3-19.5 g/l], the mean albumin level was 20 ± 5.6g/l and the mean protidemia was 50 ± 6.9 g/l. Nephrotic syndrome was impure in 89.6 % of patients with high blood pressure in 70.5 % of cases, hematuria ≥2 + in 34.7% of cases and renal failure in 88.4 % of cases. The renal biopsy was performed in 41 patients. The most common glomerular lesions were Membranous nephropathy (29 %) followed by amyloidosis (27 %). NS was secondary in 63.2 % of cases mainly to amyloidosis (35.8 %) and diabetes (19.8 %). Idiopathic nephropaty was dominated by membranous nephropathy (11.3 %) and primitive membranoproliferative glomerulonephritis (MPGN) (6.6 %). At the end of follow-up, 35 % of patients achieved complete or partial remission and 58.5 % progressed to ESRD. The multivariate study found as independent risk factors of progression to ESRD uremia ≥ 17 mmol/l (ORa =33.2 [1.3 - 837.7]; p Conclusion Elderly NS was characterized by a poor prognosis, in particular secondary to delayed and non-uniform treatment strategies, hence the need for rising physician awarness about this decease and consultation on a standardized treatment strategies.

Background The effect of renal biopsy on the prognosis of elderly patients with chronic kidney disease remains unclear. Thus, in this study, we aimed to evaluate the relationship between renal biopsy and renal survival in this population.Methods In this multi-centre retrospective study, the baseline characteristics among three groups were balanced by propensity matching. All patients were divided into three groups according to age and renal biopsy. The clinicopathological features at biopsy and renal outcomes during the follow-up were collected and analysed. Renal outcomes were defined as estimated glomerular filtration rate < 15 mL/min/1.73 m2, dialysis, renal transplantation, or death. The prognostic effects of renal biopsy were evaluated using Cox regression models. Results A total of 1313 patients were identified. After propensity matching, 390 patients were selected and divided into three groups. After a total follow-up period of 55 months, 20 (13.3%) patients (47.6% group 1 vs 7.41% group 2 vs 39.1% group 3) reached renal outcomes. No significant differences were found in renal outcomes among aged patients whether they underwent renal biopsy or not. Cox regression analysis revealed risk factors in aged patients including low albumin and high levels of proteinuria and serum creatinine (P < 0.05). Platelet count was significant only in aged patients who underwent renal biopsy (hazard ratio: 0.642, P < 0.05). Conclusion In conclusion, renal biopsy in the elderly has not shown benefits in terms of renal survival, conservative treatment appears to be a viable therapeutic option in the management of those people.

Background Antibody-mediated rejection (ABMR) is the leading cause of kidney graft loss worldwide. Criteria for acute humoral rejection (currently labeled active humoral rejection) established by the 2007 Banff classification are highly specific but lack sensitivity. Modifications to the Banff classification were introduced for its 2013 and 2017 versions in order to identify more cases of this entity. Purpose We intend to demonstrate that, compared to its 2007 version, the 2017 Banff classification bears an improved capacity for graft loss prediction when histologic criteria for active ABMR are met. Patients and methods Single-center retrospective cohort study. A random sample of 201 kidney recipients who underwent a graft biopsy since January 2004 was analyzed. Patients were classified as ever developing histologic characteristics of acute ABMR (2007 Banff) or not and renal survival between groups was compared. The same patients were then classified as ever developing histologic characteristics of active ABMR (2017 Banff) or not and renal survival was again compared. Presence of circulating donor-specific antibodies (DSA) was not taken into consideration. Results Patients were followed for a median 13.9 ± 7.9 years, during which grafts were biopsied on 537 occasions (2.7 ± 1.6 biopsies per graft). Baseline eGFR was 73.26 ± 17.6 ml/min and baseline creatinine 1.14 ± 0.25 mg/dl. Graft loss occurred in 38 recipients (18.9%) mainly due to ABMR (60.5%). Acute ABMR (2007 Banff) was identified in 11 recipients (5.5%) and graft survival did not differ between groups with and without active ABMR occurrence (log-rank p = 0.939). Active ABMR (2017 Banff) was found in 59 recipients (29%) and graft survival was better from the second post-transplant year onward in the group of patients without active ABMR occurrence (log-rank p = 0.001). Moderate microvascular inflammation was present in 89.6% of the 48 additional patients with active ABMR. Conclusion The 2017 Banff classification identifies more patients who develop active ABMR and stratifies graft loss risk better than the 2007 version.

Background Previous randomized-controlled trials have shown that targeting higher hemoglobin (Hb) levels using high dose of ESA in non-dialysis chronic kidney disease (NDCKD) patients resulted in poorer cardiovascular outcome; however, it remains unknown how high Hb levels achieved by ESA in clinical practice dose could affect renal outcome. Methods In a multicenter prospective observational study, Japanese NDCKD patients with an estimated glomerular filtration rate (eGFR) of ≥ 6 mL/min/1.73 m2 and renal anemia (Hb

Introduction: It is recommended that IgA nephropathy (IgAN) is treated with steroids when the glomerular filtration rate (GFR) is >50 ml/min and proteinuria >1 g/day. Few studies have been performed comparing the two accepted steroid regimens (1 g/day methylprednisolone pulses for 3 consecutive days at the beginning of months 1, 3 and 5, followed by 0.5 mg/kg prednisolone on alternate days vs. 1 mg/kg/day oral prednisolone). The aim of this study was to compare these two steroid regimens in IgAN treatment. Methods: We selected 39 patients with biopsy-proven IgAN treated with steroids. Mean age at diagnosis was 37.5 years, 23 males (59%), baseline proteinuria (Uprot) was 2.1 g/day and median serum creatinine (SCr) was 1.5 mg/dl. The mean follow-up period was 56 months. Twenty-five patients (64%) were treated with methylprednisolone pulses and 14 (36%) with oral steroids. Results: Patients treated with steroid pulses presented lower relapse risk, defined as the reappearance of Uprot >1 g/day and an Uprot increase of more than 50% (incidence rate ratio of 0.18, 95% CI 0.02–0.5). The Kaplan–Meier analysis showed longer relapse-free period (p = 0.019). This result was confirmed in a multivariate analysis (p = 0.026). However, we did not find other differences between the two steroid regimens. Conclusions: In comparison to oral steroids, the intravenous pulse regimen was associated with a lower risk of relapse in IgAN, a known independent negative predictor of renal survival. No differences were found regarding the other renal outcomes. Resumen: Introducción: Se recomienda el tratamiento de la nefropatía por IgA (NIgA) con esteroides cuando el índice de filtración glomerular (IFG) > 50 ml/min y proteinuria > 1 g/día. Pocos han sido los estudios realizados comparando los 2 esquemas de esteroides aceptados (1 g/día de metilprednisolona en pulsos durante 3 días consecutivos en el principio de los meses 1, 3 y 5 seguido de 0,5 mg/kg en días alternos de prednisolona vs. 1 mg/kg/día de prednisolona oral). El objetivo de este estudio fue comparar estos 2 esquemas de esteroides en el tratamiento de la NIgA. Métodos: Fueron seleccionados 39 pacientes con NIgA demostrada por biopsia y tratados con esteroides. La edad media al diagnóstico fue de 37,5 años, 23 varones (59%), proteinuria basal (Uprot) 2,1 g/día y la creatinina sérica mediana (SCR) 1,5 mg/dl. El periodo medio de seguimiento fue de 56 meses. Veinticinco de los pacientes (64%) fueron tratados con pulsos de metilprednisolona y 14 (36%) con esteroides orales. Resultados: Los pacientes tratados con pulsos de esteroides presentan menor riesgo de recaída, definido como la reaparición de una Uprot > 1 g/día y aumento de más del 50% de la Uprot (razón de tasa de incidencia: 0,18; IC 95%: 0,02-0,5) y el Kaplan-Meier mostró período más largo libre de recaída (p = 0,019). Este resultado se confirmó en un análisis multivariante (p = 0,026). Sin embargo, no se encontraron otras diferencias entre los esquemas de esteroides. Conclusiones: En comparación con los esteroides orales, el esquema en pulsos intravenosos se relacionó con un menor riesgo de recaída en la NIgA, un conocido predictor negativo independiente de la supervivencia renal. No se encontraron diferencias en cuanto a los otros outcomes renales. Keywords: IgA nephropathy, Steroid regimens, Renal survival, Palabras clave: Nefropatía por IgA, Esquemas de esteroides, Supervivencia renal

ObjectivesTo evaluate changes in demographic, clinical and histological presentation, and prognosis of lupus nephritis (LN) over time.Patients and methodsWe studied a multicentre cohort of 499 patients diagnosed with LN from 1970 to 2016. The 46-year follow-up was subdivided into three periods (P): P1 1970–1985, P2 1986–2001 and P3 2002–2016, and patients accordingly grouped based on the year of LN diagnosis. Predictors of patient and renal survival were investigated by univariate and multivariate proportional hazards Cox regression analyses. Survival curves were compared using the log-rank test.ResultsA progressive increase in patient age at the time of LN diagnosis (pConclusionsClinical presentation of LN has become less severe in the last years, leading to a better long-term renal survival.

Aim: Amyloid A amyloidosis is a rare complication of chronic inflammatory conditions. Most patients with amyloid A amyloidosis present with nephropathy and it leads to renal failure and death. We studied clinical characteristics and survival in patients with amyloid A amyloidosis. Methods: A total of 81 patients (51 males, 30 females) with renal biopsy proven amyloid A amyloidosis were analyzed retrospectively. The patients were divided into good and poor outcomes groups according to survival results. Results: Most of the patients (55.6%) had nephrotic range proteinuria at diagnosis. Most frequent underlying disorders were familial Mediterranean fever (21.2%) and rheumatoid arthritis (10.6%) in the good outcome group and malignancy (20%) in the poor outcome group. Only diastolic blood pressure in the good outcome group and phosphorus level in the poor outcome group was higher. Serum creatinine levels increased after treatment in both groups, while proteinuria in the good outcome group decreased. Increase in serum creatinine and decrease in estimated glomerular filtration rate of the poor outcome group were more significant in the good outcome group. At the time of diagnosis 18.5% and 27.2% of all patients had advanced chronic kidney disease (stage 4 and 5, respectively). Median duration of renal survival was 65 +/- 3.54 months. Among all patients, 27.1% were started dialysis treatment during the follow-up period and 7.4% of all patients underwent kidney transplantation. Higher levels of systolic blood pressure [hazard ratios 1.03, 95% confidence interval: 1-1.06, p = 0.036], serum creatinine (hazard ratios 1.25, 95% confidence interval: 1.07-1.46, p = 0.006) and urinary protein excretion (hazard ratios 1.08, 95% confidence interval: 1.01-1.16, p = 0.027) were predictors of end-stage renal disease. Median survival of patients with organ involvement was 50.3 +/- 16 months. Conclusion: Our study indicated that familial Mediterranean fever constituted a large proportion of cases and increased number of patients with idiopathic amyloid A amyloidosis. Additionally, it was observed that patient survival was not affected by different etiological causes in amyloid A amyloidosis. Resumo Objetivo: A amiloidose AA é uma complicação rara de condições inflamatórias crônicas. A maior parte dos pacientes com amiloidose AA apresenta nefropatia, que leva à insuficiência renal e à morte. Estudaram-se as características clínicas e a sobrevida em pacientes com amiloidose AA. Métodos: Analisaram-se retrospectivamente 81 pacientes (51 homens, 30 mulheres) com amiloidose AA comprovada por biópsia renal. Os pacientes foram divididos em grupos de desfecho bom e ruim de acordo com os resultados de sobrevida. Resultados: A maior parte dos pacientes (55,6%) tinha proteinúria na faixa nefrótica no momento do diagnóstico. Os distúrbios subjacentes mais frequentes foram a febre familiar do Mediterrâneo (FFM, 21,2%) e a artrite reumatoide (10,6%) no grupo de desfecho bom e a malignidade (20%) no grupo de desfecho ruim. Somente a pressão arterial diastólica no grupo de desfecho bom e o nível de fósforo no grupo de desfecho ruim foram mais elevados. Os níveis séricos de creatinina aumentaram após o tratamento em ambos os grupos, enquanto a proteinúria diminuiu no grupo de desfecho bom. O aumento na creatinina sérica e a diminuição na TFGe do grupo de desfecho ruim foram mais significativos no grupo de desfecho bom. No momento do diagnóstico, 18,5% e 27,2% de todos os pacientes tinham doença renal crônica avançada (estágios 4 e 5, respectivamente). A duração média da sobrevida renal foi de 65 ± 3,54 meses. Entre todos os pacientes, 27,1% iniciaram tratamento de diálise durante o período de seguimento e 7,4% de todos os pacientes foram submetidos a transplante renal. Níveis elevados de pressão arterial sistólica [taxas de risco (HR) 1,03, intervalo de confiança (IC) de 95%: 1 a 1,06, p = 0,036], creatinina sérica (HR 1,25, IC 95%: 1,07 a 1,46, p = 0,006) e excreção urinária de proteínas (HR 1,08, IC 95%: 1,01 a 1,16, p = 0,027) foram preditores de doença renal terminal. A mediana da sobrevida de pacientes com comprometimento de órgãos foi de 50,3 ± 16 meses. Conclusão: O presente estudo indicou que a FFM constituiu uma grande proporção de casos e crescente quantidade de pacientes com amiloidose AA idiopática. Adicionalmente, observou-se que a sobrevida do paciente não foi afetada pelas diferentes causas etiológicas na amiloidose AA.

Background Autosomal dominant polycystic disease (ADPKD) often results in renal failure. Recently, allelic influences of PKD1 mutation types on renal survival were extensively investigated. Here, we analyzed integrated influences of PKD1 mutation types and positions on renal survival. Methods We included 338 (82 pedigrees) and 72 (12 pedigrees) patients with PKD1 and PKD2 mutations, respectively, identified through comprehensive gene analysis of 101 probands with ADPKD. Genetic testing was performed using next-generation sequencing, long-range PCR, and multiplex ligation-dependent probe amplification. Pathogenic mutations were identified by a software package-integrated seven databases and provided access to five cloud-based computing systems. Results Mean renal survivals of carriers with PKD1 non-truncating-type mutations at positions upstream of G-protein-coupled receptor proteolytic site (GPS-upstream domain), transmembrane domain, or cytoplasmic C-terminal tail (CTT) domain were 70.2, 67.0, and 50.1 years, respectively (P

Resumen Antecedentes: Los registros de biopsias renales permiten la recogida de datos histopatológicos que, puestos en su conjunto, ayudan a comprender enfermedades y su historia natural. Objetivos: Analizar los datos del Registro de Glomerulonefritis de Castilla-La Mancha (GLOMANCHA) y la evolución de las diferentes enfermedades biopsiadas (1994-2008). Métodos: Se recogieron las 6 enfermedades biopsiadas más prevalentes durante los 14 años (941 biopsias) en 5 hospitales de la comunidad autónoma. En 2008 se evaluó la situación vital y renal de los pacientes y se analizaron los factores asociados a dicha situación en cada enfermedad. Resultados: De las 941 biopsias, el 59% fueron de varones con una edad media de 48 ± 18 años. En el momento de la biopsia la mediana de filtrado glomerular (FG) era de 50,3 (25,5-76,3) ml/min/1,73 m2 y la de proteinuria de 3,4 (1,5-6,4) g al día. La enfermedad más frecuente fue la nefropatía lúpica, seguida de la glomeruloesclerosis focal y segmentaria, y de la membranosa. El mejor pronóstico renal durante el seguimiento (media 7,3 ± 4,8 años) fue el de la nefropatía lúpica y la nefropatía por cambios mínimos; la glomeruloesclerosis focal y segmentaria y las glomerulonefritis rápidamente progresivas de tipo 3 tuvieron el peor pronóstico renal. Esta última, además, tuvo el peor pronóstico vital. Conclusiones: GLOMANCHA demuestra el mal pronóstico de las glomerulonefritis rápidamente progresivas de tipo 3, a diferencia de la nefropatía por cambios mínimos y lúpica. La función renal es un predictor independiente de supervivencia renal y de mortalidad en nuestra población. Abstract Background: Renal biopsy registries allow histopathological data to be collected to improve knowledge of different pathologies and their natural history. Aim: To analyse the data of the Castilla La Mancha Glomerulonephritis Registry (GLOMANCHA) and the evolution of the different biopsy-proven pathologies between 1994 and 2008. Methods: The 6 most common biopsy-proven pathologies were collected during the 14 years of the study (941 biopsies) in the 5 participant centres of the autonomous community. In 2008, we assessed patient renal survival and mortality and we evaluated associated factors to each situation for each pathology. Results: Of the 941 biopsies, 59% belonged to men, with a mean age of 48 ± 18 years. At the time of the biopsy, the median glomerular filtration rate was 50.3 (25.5-76.3) ml/min/1,73 m2 and median proteinuria was 3.4 (1.5-6.4) grams per day. The most common pathology were lupus nephropathy, followed by focal segmental glomerulosclerosis and membranous nephropathy. Lupus nephropathy and minimal change disease achieved the best renal prognosis during follow-up (mean 7.3 ± 4.8 years). Rapidly progressive glomerulonephritis type 3 and focal segmental glomerulosclerosis had the worst renal prognosis. In addition, rapidly progressive glomerulonephritis type 3 presented the worst vital prognosis. Conclusions: In GLOMANCHA, we demonstrate the poor prognosis of rapidly progressive glomerulonephritis type 3, in contrast to minimal change disease or lupus nephropathy. Renal function is an independent predictor of renal survival and mortality in this study.

ResumenAntecedentesLos registros de biopsias renales permiten la recogida de datos histopatológicos que, puestos en su conjunto, ayudan a comprender enfermedades y su historia natural.ObjetivosAnalizar los datos del Registro de Glomerulonefritis de Castilla-La Mancha (GLOMANCHA) y la evolución de las diferentes enfermedades biopsiadas (1994-2008).MétodosSe recogieron las 6 enfermedades biopsiadas más prevalentes durante los 14 años (941 biopsias) en 5 hospitales de la comunidad autónoma. En 2008 se evaluó la situación vital y renal de los pacientes y se analizaron los factores asociados a dicha situación en cada enfermedad.ResultadosDe las 941 biopsias, el 59% fueron de varones con una edad media de 48±18 años. En el momento de la biopsia la mediana de filtrado glomerular (FG) era de 50,3 (25,5-76,3) ml/min/1,73 m2 y la de proteinuria de 3,4 (1,5-6,4) g al día. La enfermedad más frecuente fue la nefropatía lúpica, seguida de la glomeruloesclerosis focal y segmentaria, y de la membranosa. El mejor pronóstico renal durante el seguimiento (media 7,3±4,8 años) fue el de la nefropatía lúpica y la nefropatía por cambios mínimos; la glomeruloesclerosis focal y segmentaria y las glomerulonefritis rápidamente progresivas de tipo 3 tuvieron el peor pronóstico renal. Esta última, además, tuvo el peor pronóstico vital.ConclusionesGLOMANCHA demuestra el mal pronóstico de las glomerulonefritis rápidamente progresivas de tipo 3, a diferencia de la nefropatía por cambios mínimos y lúpica. La función renal es un predictor independiente de supervivencia renal y de mortalidad en nuestra población.AbstractBackgroundRenal biopsy registries allow histopathological data to be collected to improve knowledge of different pathologies and their natural history.AimTo analyse the data of the Castilla La Mancha Glomerulonephritis Registry (GLOMANCHA) and the evolution of the different biopsy-proven pathologies between 1994 and 2008.MethodsThe 6 most common biopsy-proven pathologies were collected during the 14 years of the study (941 biopsies) in the 5 participant centres of the autonomous community. In 2008, we assessed patient renal survival and mortality and we evaluated associated factors to each situation for each pathology.ResultsOf the 941 biopsies, 59% belonged to men, with a mean age of 48±18 years. At the time of the biopsy, the median glomerular filtration rate was 50.3 (25.5-76.3) ml/min/1,73 m2 and median proteinuria was 3.4 (1.5-6.4) grams per day. The most common pathology were lupus nephropathy, followed by focal segmental glomerulosclerosis and membranous nephropathy. Lupus nephropathy and minimal change disease achieved the best renal prognosis during follow-up (mean 7.3±4.8 years). Rapidly progressive glomerulonephritis type 3 and focal segmental glomerulosclerosis had the worst renal prognosis. In addition, rapidly progressive glomerulonephritis type 3 presented the worst vital prognosis.ConclusionsIn GLOMANCHA, we demonstrate the poor prognosis of rapidly progressive glomerulonephritis type 3, in contrast to minimal change disease or lupus nephropathy. Renal function is an independent predictor of renal survival and mortality in this study.

Background: We aimed to evaluate the effect of immunosuppressant therapy for immunoglobulin A nephropathy (IgAN) patients with mild proteinuria (

Background:The role of ANCA type is well established for the risk of relapses of ANCA-associated vasculitis (AAV). However their association with renal involvement and its outcomes is less well understood.Objectives:To assess clinical and morphological features of ANCA-associated glomerulonephritis (ANCA-GN) and renal survival in ANCA-negative patients, proteinase-3-ANCA (pr3-ANCA) positive and myeloperoxidase-ANCA (MPO-ANCA) positive patients.Methods:We enrolled 53 patients with AAV, diagnosed according to Chapel Hill Consensus Conference (2012) definition and/or ACR (1990) criteria, with histologically proven renal involvement. There were 13 (24.5%) males, median age at onset was 48 (33; 57) years. Seven patients were ANCA-negative (13.3%), 17 (32.0%) patients were pr-3-ANCA positive and 29 (54.7%) patients were MPO-ANCA-positive. ANCA-associates glomerulonephritis (ANCA-GN) class was established according to Berden et al classification.1We retrospectively assessed ANCA renal risk score (ARRS) at disease onset.2Twelve patients (22.6%) developed end-stage renal disease (ESRD) after a median of 12 (6.5; 28) months. Renal survival rates were assessed by Kaplan-Meier method and compared by log-rank test.Results:The only significant difference was median BVAS score which was significantly higher in pr3-ANCA-positive (18 (17;20)) than in MPO-ANCA positive patients (15 (12; 18), p=0.012). Creatinine levels, eGFR, percentage of glomeruli with crescents, global sclerosis, and interstitial fibrosis and tubular atrophy didn’t depend on the presence of ANCA or type of the antibodies. The proportion of patients with focal, crescentic, mixed of sclerotic class of ANCA-GN was similar in all groups. There was no significant difference in the numbers of patients with low, medium or high risk of ESRD according to ARRS. One- and three-year renal survival rates were similar in ANCA-negative (81.7% and 60.0% respectively) and ANCA-positive patients (84.2% and 74.6% respectively, Figure 1A). One-year and three-year survival rates were higher in MPO-ANCA-positive (84.4% and 84.4% respectively) than in pr3-ANCA-positive patients (73.1% and 50.1% respectively), however the difference was not statistically significant (Figure 1B).Figure 1.Kaplan-Meier curves showing renal survival in ANCA-positive and ANCA-negative patients (A), and pr3-ANCA-positive and MPO-ANCA-positive patients (B)Conclusion:Our small study indicates that clinical and morphological features of renal involvement, as well as renal survival are similar in ANCA-negative and ANCA-positive patients and don’t depend on the type of ANCA.References:[1]Berden AE, Ferrario F, Hagen EC, et al. Histopathologic Classification of ANCA-Associated Glomerulonephritis. J Am Soc Nephrol. 2010;21(10):1628–1636.[2]Brix RB, Noriega M, Tennstedt P, et al. Development and validation of a renal risk score in ANCA-associated glomerulonephritis. Kidney Int. 2018;94(6):1177-1188.Disclosure of Interests: :Nikolai Bulanov Grant/research support from: This work was supported by the 5-100 Project, Sechenov University, Moscow, Ekaterina Stolyarevich: None declared, Anastasiia Zykova: None declared, Elizaveta Safonova: None declared, Elena Shchegoleva: None declared, Ekaterina Kuznezova: None declared, Mayra Bulanova: None declared, Pavel Novikov Grant/research support from: This work was supported by the 5-100 Project, Sechenov University, Moscow, Sergey Moiseev Grant/research support from: This work was supported by the 5-100 Project, Sechenov University, Moscow

Malignant hypertension is listed among the causes of secondary thrombotic microangiopathy (TMA), but pathogenic mutations in complement genes have been reported in patients with hypertension-induced TMA. Here we investigated the frequency and severity of hypertension in 55 patients with primary atypical hemolytic uremic syndrome (aHUS). A genetic analysis was performed in all patients, and funduscopic examination was performed in all the patients with Grades 2 and 3 hypertension. A cohort of 110 patients with malignant hypertension caused by diseases other than aHUS served as control. Thirty-six patients with aHUS presented Grade 2 or Grade 3 hypertension and funduscopic examination showed malignant hypertension in 19. Genetic abnormalities in complement were found in 19 patients (37% among patients with malignant hypertension). Plasmapheresis was performed in 46 patients and 26 received eculizumab. Renal and hematological responses were significantly lower after plasmapheresis (24%) than after eculizumab (81%). Renal survival was significantly higher in patients treated with eculizumab (85% at one, three and five years) compared to patients who did not receive this treatment (54%, 46% and 41%), respectively. Response to eculizumab was independent of hypertension severity and the presence of complement genetic abnormalities. Among patients with malignant hypertension caused by other diseases the prevalence of TMA was very low (5%). Thus, severe and malignant hypertension are common among patients with aHUS and eculizumab treatment leads to a higher renal survival when compared to plasmapheresis. However, TMA is uncommon among patients presenting with malignant hypertension caused by diseases other than aHUS., Work in this study was supported by the Instituto de Salud Carlos III /Fondo Europeo de Desarrollo Regional (ISCIII/FEDER) grants PI13/02502, PICI14/00350, and PI16/01685 (to MP), and grants PI13/00802, PI14/00883 and PI17/00130 (to JAM.); the ISCIII/FEDER Programa Miguel Servet, grants CP10/00479 and CPII16/00017 (to JAM); the Spanish “Ministerio de Economía y Competitividad/FEDER” [SAF2015-66287-R] (to SRdeC); the Autonomous Region of Madrid (S2017/BMD-3673) (to SRdeC, EA and MP); Red de Investigación Renal (RedInRen) (RD12/0021/0029) (to MP), the “Fundación Inocente” (Madrid, Spain).] (to SRdC), and the Spanish Society of Nephrology and Fundación Renal Ínigo Álvarez de Toledo (FRIAT) (to JAM).

International audience; The course of autosomal dominant polycystic kidney disease (ADPKD) varies among individuals, with some reaching ESRD before 40 years of age and others never requiring RRT. In this study, we developed a prognostic model to predict renal outcomes in patients with ADPKD on the basis of genetic and clinical data. We conducted a cross-sectional study of 1341 patients from the Genkyst cohort and evaluated the influence of clinical and genetic factors on renal survival. Multivariate survival analysis identified four variables that were significantly associated with age at ESRD onset, and a scoring system from 0 to 9 was developed as follows: being male: 1 point; hypertension before 35 years of age: 2 points; first urologic event before 35 years of age: 2 points; PKD2 mutation: 0 points; nontruncating PKD1 mutation: 2 points; and truncating PKD1 mutation: 4 points. Three risk categories were subsequently defined as low risk (0-3 points), intermediate risk (4-6 points), and high risk (7-9 points) of progression to ESRD, with corresponding median ages for ESRD onset of 70.6, 56.9, and 49 years, respectively. Whereas a score ≤3 eliminates evolution to ESRD before 60 years of age with a negative predictive value of 81.4%, a score \textgreater6 forecasts ESRD onset before 60 years of age with a positive predictive value of 90.9%. This new prognostic score accurately predicts renal outcomes in patients with ADPKD and may enable the personalization of therapeutic management of ADPKD

Background/Aims: Treatment of advanced Immunoglobulin A nephropathy (IgAN) patients with estimated glomerular filtration rate (eGFR) below 45 mL/min per 1.73 m2 remains inconsistent. The aim of this study is to compare the effects of corticosteroid and immunosuppressant therapies among these patients. Methods: A total of 201 adult patients with advanced IgAN (eGFR < 45 mL/min/1.73 m2 and proteinuria > 1 g/24h at biopsy) grouped into supportive care (SC), steroids alone (CS), and steroids plus immunosuppressant (IT) groups, were investigated between 30th December 2002 and 30th June 2016. The primary endpoint was the combined endpoint of a 50% decline in eGFR and/or end stage renal disease (ESRD: eGFR < 15 mL/min/1.73 m2 or maintenance renal replacement treatment). Responses to therapy included complete remission (CR: urinary protein excretion < 0.5 g/24h, with eGFR decrease less than 10% baseline), partial remission (PR: proteinuria decrease by > 50% baseline, with eGFR decrease less than 10% baseline), no response (NR: proteinuria decrease < 50% baseline, or eGFR decrease > 10% baseline) and ESRD. Kaplan–Meier and Cox proportional hazards analyses were performed. Results: During the follow-up period (37.2 ± 22.7 months), 6.8% patients in SC group, 25.0% in CS group, and 38.0% in IT group achieved CR or PR, while 78.4%, 62.5% and 49.3% patients in these 3 groups reached primary endpoint respectively (p < 0.001). Three-year renal survival rates in SC and combined immunosuppressive treatment groups (CS and IT groups) were 33.8% vs 51.2% (p = 0.02), and 5-year renal survival rates were 12.2% vs 21.3% (p = 0.1) respectively. Multivariate Cox regression analysis showed that hypertension (HR = 2.44, 95% CI 1.51–3.95; p < 0.001), Scr (HR = 1.01, 95% CI 1.00-1.01; p < 0.001), T1-T2 lesion (HR = 1.99, 95% CI 1.35–2.93; p = 0.001) were independent indicators of poor renal outcome. Conclusion: Immunosuppressive treatment (CS and IT therapy) may improve short-term renal outcome compared with supportive treatment in advanced IgAN patients.

Objective.To determine the association between crescents and renal outcomes, and the implications on therapeutic choices.Methods.There were 231 patients with biopsy-proven proliferative lupus nephritis (PLN) who were divided into 4 groups: 59 patients were in the noncrescent group (NC); 59 patients exclusively with segmental crescents were in the segmental crescent group (SC); patients with circumferential crescents were categorized into 2 groups according to the crescentic ratio (C1 had 64 patients with ≤ 25%, and C2 had 49 patients with > 25%). Their baseline laboratory tests, histopathological manifestations, and outcomes were compared.Results.Remission rates in NC, SC, C1, and C2 groups were 92.1%, 85.4%, 95.0%, and 76.1%, respectively. Fewer patients in the C2 group achieved complete remission than the other 3 groups. For longterm outcomes evaluated by serum creatinine (SCr) doubling or endstage renal disease (ESRD), the renal survival rate was lowest in the C2 group (p = 0.003). Including clinical and pathological variables in the Cox proportional hazard regression model separately, the multivariate analysis revealed that these were independent risk factors for SCr doubling or ESRD: baseline SCr (with every 1 mg/dl increase: HR = 1.834, 95% CI 1.465–2.296; p < 0.001), hemoglobin (with every 1 g/l increase: HR = 0.970, 95% CI 0.947–0.992; p = 0.009), the proportions of cellular crescents (with every 1% increase: HR = 1.040, 95% CI 1.015–1.066; p = 0.002) and fibrocellular crescents (with every 1% increase: HR = 1.085, 95% CI 1.013–1.163; p = 0.020), and severe renal tubular atrophy (HR = 5.348, 95% CI 1.278–22.373; p = 0.022).Conclusion.PLN with crescents > 25% had worse renal outcomes both in short and long terms. Proportions of cellular and fibrocellular crescents were independent risk factors for poor renal survival.

Immunoglobulin A nephropathy (IgAN) is the most frequent glomerular disease worldwide and a leading cause of end-stage renal disease. Particularly challenging to the clinician is the early identification of patients at high risk of progression, an estimation of the decline in renal function, and the selection of only those that would benefit from additional immunosuppressive therapies. Nevertheless, the pathway to a better prognostication and to the development of targeted therapies in IgAN has been paved by recent understanding of the genetic and molecular basis of this disease. Merging the data from the Oxford Classification validation studies and prospective treatment studies has suggested that a disease-stratifying algorithm would be appropriate for disease management, although it awaits validation in a prospective setting. The emergence of potential noninvasive biomarkers may assist traditional markers (proteinuria, hematuria) in monitoring disease activity and treatment response. The recent landmark trials of IgAN treatment (STOP-IgAN and TESTING trials) have suggested that the risks associated with immunosuppressive therapy outweigh the benefits, which may shift the treatment paradigm of this disease. While awaiting the approval of the first therapies for IgAN, more targeted and less toxic immunotherapies are warranted. Accordingly, the targeting of complement activation, the modulation of mucosal immunity, the antagonism of B-cell activating factors, and proteasomal inhibition are currently being evaluated in pilot studies for IgAN treatment.

Glomerular filtration rate (GFR) in patients with chronic kidney disease (CKD) identifies patients at risk for death or end-stage renal disease (ESRD). CKD staging by GFR should incorporate proteinuria to augment risk stratification. We therefore tested the predictive power of the combination of GFR with proteinuria in patients with different histologically-diagnosed types of glomerulonephritis (GN).In a retrospective analysis, 2,687 patients with different forms of GN from 123 Austrian centres were investigated. Full data sets were available from 1,892 subjects. Classes of CKD on the basis of estimated GFR (eGFR) and of proteinuria grouped as1, 1-3.5, and3.5 g/24 h were tested for their association with all-cause mortality and ESRD.During a median follow-up of 130 months [interquartile range (IQR) 90; 178] 478 patients (25.3 %) died. Median eGFR was 49 ml/min/1.73 m(2) (IQR 24; 81) and proteinuria 3.8 g/24 h (IQR 1.7; 8.0). Adjusted multivariate Cox regression indicated that renal survival but not overall survival is related to proteinuria3.5 g/24 h [as opposed to1 g/24 h; hazard ratio (HR) 1.91] and shows progression to ESRD. However, subgroup analyses revealed that this risk with proteinuria3.5 g/24 h exists only in patients with immunoglobulin (Ig)A GN (HR 4.93), miscellaneous GN (HR 1.74), and CKD stage 5 (HR 2.50). Additionally, proteinuria is a risk factor for renal survival in males more than in females with GN and proteinuria3.5 g/24 h (HR 1.91).Proteinuria is a strong risk factor for renal survival particularly in patients with proteinuria3.5 g/24 but not for all types of GN, nor for all CKD stages. Proteinuria is not a risk factor for overall survival in patients with GN.

Objective: This study aimed to determine the value of hypocomplementemia in predicting the renal and patient survival of patients with antineutrophil cytoplasmatic antibody-associated vasculitis (AAV). Methods: A retrospective analysis of 30 consecutive patients who were diagnosed with AAV and followed at our hospital from 1996 to 2011 was performed. Renal outcome was determined by the Modification of Diet in Renal Disease equation. Disease outcome measures included patient survival and accrual of chronic kidney disease (CKD) defined as an estimated glomerular filtration rate (eGFR) 2 from the date of diagnosis. Logistic regression analysis was used to identify predictors of survival. Results: At presentation, 6 (20%) patients had a low C3 level, which was significantly associated with older age (p = 0.009), higher C-reactive protein (p = 0.02), a lower eGFR (p = 0.03), and anti-MPO antibody positivity (p = 0.03). A low C3 level at presentation was significantly associated with a reduced eGFR at the last study visit (p = 0.015, OR = 11; 95% CI 1.27-95.15). During a mean follow-up of 9.0 ± 6.2 years, 8 (26.6%) patients had accrued CKD that was significantly associated with low C3 levels at presentation (p = 0.002, OR = 22; 95% CI 2.36-204.7). Mortality was significantly associated with low serum C3 levels at presentation (p = 0.02). Conclusion: We found that a low serum C3 level at the time of diagnosis was significantly associated with reduced renal and patient survival in patients with anti-MPO AAV. Our results suggest a role for complement activation in the pathogenesis of AAV.

Background and aims Raising evidence supported a prognostic utility of tubulointerstitial lesions in lupus nephritis (LN). The exact prevalence of tubulointerstitial abnormalities and its predictive value among paediatric onset systemic lupus erythematous (pSLE) cases, however, remained unknown. Methods Sixty-seven pSLE subjects diagnosed with LN with initial renal samples available were enrolled and followed for an average of 6.43±3.06 years. Renal histology was evaluated according to the International Society of Nephrology/Renal Pathology Society classification, National Institute of Health classification and tubulointerstitial activity index (TIAI). Results Tubulointerstitial injuries were observed in 38.81% of all LN cases, including 13.33% with non-proliferative lupus nephritis (nPLN) and 46.15% of with proliferative lupus nephritis (PLN). Tubulointerstitial injuries occurred solitarily in cases with nPLN(13.33%), but always associated glomerular changes and significantly impacted renal survival (p=0.032) among those with PLN. TIAI associated glomerular abnormalities (p=0.031) but did not correlate renal performance or subsequent outcome (p=0.445). Among the chronicity index, it was the chronic tubulointerstitial lesions which provided prognostic information (p=0.012). We observed a synergistic effect of all tubulointerstitial abnormalities rather than an individual factor attributed the prognostic utility (p=0.025 vs. p=0.083, 0.055, 0.354). Finally, considering tubulointerstitial injuries in PLN further discriminated subsequent renal outcome (p=0.006). Conclusions The prevalence and clinical significance of tubulointerstitial abnormalities were similar among the pSLE and the adult population. With its importance in identifying those at risk of renal failure, histologic classification considering tubulointerstitial lesions may potentially assist outcome prediction.

Resumo Objetivo A amiloidose AA e uma complicacao rara de condicoes inflamatorias cronicas. A maior parte dos pacientes com amiloidose AA apresenta nefropatia, que leva a insuficiencia renal e a morte. Estudaram‐se as caracteristicas clinicas e a sobrevida em pacientes com amiloidose AA. Metodos Analisaram‐se retrospectivamente 81 pacientes (51 homens, 30 mulheres) com amiloidose AA comprovada por biopsia renal. Os pacientes foram divididos em grupos de desfecho bom e ruim de acordo com os resultados de sobrevida. Resultados A maior parte dos pacientes (55,6%) tinha proteinuria na faixa nefrotica no momento do diagnostico. Os disturbios subjacentes mais frequentes foram a febre familiar do Mediterrâneo (FFM, 21,2%) e a artrite reumatoide (10,6%) no grupo de desfecho bom e a malignidade (20%) no grupo de desfecho ruim. Somente a pressao arterial diastolica no grupo de desfecho bom e o nivel de fosforo no grupo de desfecho ruim foram mais elevados. Os niveis sericos de creatinina aumentaram apos o tratamento em ambos os grupos, enquanto a proteinuria diminuiu no grupo de desfecho bom. O aumento na creatinina serica e a diminuicao na TFGe do grupo de desfecho ruim foram mais significativos no grupo de desfecho bom. No momento do diagnostico, 18,5% e 27,2% de todos os pacientes tinham doenca renal cronica avancada (estagios 4 e 5, respectivamente). A duracao media da sobrevida renal foi de 65 ± 3,54 meses. Entre todos os pacientes, 27,1% iniciaram tratamento de dialise durante o periodo de seguimento e 7,4% de todos os pacientes foram submetidos a transplante renal. Niveis elevados de pressao arterial sistolica [taxas de risco (HR) 1,03, intervalo de confianca (IC) de 95%: 1 a 1,06, p = 0,036], creatinina serica (HR 1,25, IC 95%: 1,07 a 1,46, p = 0,006) e excrecao urinaria de proteinas (HR 1,08, IC 95%: 1,01 a 1,16, p = 0,027) foram preditores de doenca renal terminal. A mediana da sobrevida de pacientes com comprometimento de orgaos foi de 50,3 ± 16 meses. Conclusao O presente estudo indicou que a FFM constituiu uma grande proporcao de casos e crescente quantidade de pacientes com amiloidose AA idiopatica. Adicionalmente, observou‐se que a sobrevida do paciente nao foi afetada pelas diferentes causas etiologicas na amiloidose AA.

Hematuria is a cardinal symptom in IgA nephropathy, but its influence on the risk of disease progression has been scarcely investigated. We followed a cohort of 112 patients with IgA nephropathy for a mean±SEM period of 14±10.2 years, during which clinical and analytic risk factors (including urine sediment examination) were regularly recorded. According to the magnitude of time-averaged hematuria, we classified patients as those with persistent hematuria and those with negative or minimal hematuria. We also classified patients according to the magnitude of time-averaged proteinuria (>0.75 or ≤0.75 g/d). The proportion of patients reaching ESRD or a 50% reduction of renal function was significantly greater among patients with persistent hematuria than patients with minimal or negative hematuria (30.4% and 37.0% versus 10.6% and 15.2%, respectively; P=0.01). Multivariable analysis revealed time-averaged hematuria, time-averaged proteinuria, renal function at baseline, and the presence of tubulointerstitial fibrosis on renal biopsy as independent predictors of ESRD. After hematuria disappearance, which occurred in 46% of the patients, the rate of renal function decline changed from -6.45±14.66 to -0.18±2.56 ml/min per 1.73 m2 per year (P=0.001). Patients with time-averaged proteinuria >0.75 g/d had significantly poorer renal survival than those with time-averaged proteinuria ≤0.75 g/d. However, on further classification by time-averaged hematuria, only those patients with time-averaged proteinuria >0.75 g/d and persistent hematuria had significantly worse renal survival than those in the other three groups. In conclusion, remission of hematuria may have a significant favorable effect on IgA nephropathy outcomes.

A prospective randomised trial to compare two different durations of maintenance immunosuppressive therapy for the prevention of relapse in anti-neutrophil cytoplasmic antibodies (ANCA)-associated vasculitis (AAV).Patients with AAV were recruited 18-24 months after diagnosis if they were in stable remission after cyclophosphamide/prednisolone-based induction followed by azathioprine/prednisolone maintenance therapy. They were randomised (1:1) to receive continued azathioprine/prednisolone to 48 months from diagnosis (continuation group) or to withdraw azathioprine/prednisolone by 24 months (withdrawal group). The primary endpoint was the relapse risk, from randomisation to 48 months from diagnosis.One hundred and seventeen patients were randomised and 110 remained to the trial end. At entry, median serum creatinine was 116 μmol/L (range 58-372), 53% were ANCA positive. The percentage of patients presenting with relapse was higher in the withdrawal than in the continuation treatment group (63% vs 22%, p0.0001, OR 5.96, 95% CI 2.58 to 13.77). ANCA positivity at randomisation was associated with relapse risk (51% vs 29%, p=0.017, OR 2.57, 95% CI 1.16 to 5.68). Renal function, ANCA specificity, vasculitis type and age were not predictive of relapse. Severe adverse events were more frequent in the continuation than withdrawal groups (nine vs three events), but the continuation group had better renal outcome (0 vs 4 cases of end-stage renal disease), with no difference in patient survival.Prolonged remission maintenance therapy with azathioprine/prednisolone, beyond 24 months after diagnosis reduces relapse risk out to 48 months and improves renal survival in AAV.ISRCTN13739474.

The care of children with lupus nephritis (LN) has changed dramatically over the past 50 y. The majority of patients with childhood-onset systemic lupus erythematosus (cSLE) develop LN. In the 1960's, prognosis in children was worse than in adults; therapies were limited and toxic. Nearly half of cases resulted in death within 2 y. Since this time, several diagnostic recommendations and disease-specific indices have been developed to assist physicians caring for patients with LN. Pediatric researchers are validating and adapting these indices and guidelines for the treatment of LN in cSLE. Classification systems, activity, and chronicity indices for kidney biopsy have been validated in pediatric cohorts in several countries. Implementation of contemporary immunosuppressive agents has reduced treatment toxicity and improved outcomes. Biomarkers sensitive to LN in children have been identified in the kidney, urine, and blood. Multi-institutional collaborative networks have formed to address the challenges of pediatric LN research. Considerable variation in evaluation and treatment has been addressed for proliferative forms of LN by development of consensus treatment practices. Patient survival at 5 y is now 95-97% and renal survival exceeds 90%. Moreover, international consensus exists for quality indicators for cSLE that consider the unique aspects of chronic disease in childhood.

Summary Tubulointerstitial fibrosis mediates the development of end-stage renal disease from renal injuries of all etiologies and is considered an important predictor of renal survival. Transforming growth factor-β (TGF-β) is one of the most important growth factors that promotes tubulointerstitial fibrosis, but the mechanisms whereby this occurs are not well defined. This is because TGF-β has pleiotropic effects that depend on the target cell type. This review discusses how TGF-β signaling in each of the relevant cell types (eg, tubular epithelium, fibroblasts) may contribute to tubulointerstitial fibrosis progression and suggests ways in which future research can improve our understanding of TGF-β–mediated tubulointerstitial fibrosis.

The renal outcome in patients with primary hyperoxaluria type 1 is partly determined by AGXT mutations, including but not limited to the p.Gly170Arg mutation. The study by Mandrile et al. reports on the largest cohort of patients genotyped yet, with long-term renal survival and medical treatment by pyridoxine. In addition to the common p.Gly170Arg mutation, three other mutations were shown to be potentially associated with slower evolution.

Objective:Genetic polymorphisms of the renin-angiotensin-aldosterone system (RAAS) may play a pivotal role in the development and progression of diabetic nephropathy. Therefore, we aimed to investigate whether genetic variation in the RAAS is related to renal survival in patients with diabetic nephr

Objective Several factors have been identified as predictive of future renal function in children with posterior urethral valves (PUV). Our aim was to analyse upper and lower urinary tract outcome in patients with PUV, and determine any factors from the period of early management that were predictive of future renal function. Methods The charts of 67 boys (mean age 2.4 years) diagnosed with PUV were reviewed. The most common presenting symptom was dribbling in 43.2% and UTI in 28.3%. Twenty-three (34.8%) patients developed end-stage renal disease aged 1–15 years. The mean time of renal survival was calculated as 7.8 (SEM = 0.73) years. Results Incontinence in patients over 5 years old, lower urinary tract dysfunction, serum creatinine level in first year or at the time of diagnosis, and presence of vesicoureteral reflux and high-grade bilateral reflux were significant risk factors for occurrence of renal failure in the future. Lower tract dysfunction was seen in 58.6% of patients. Postnatal diagnosis and presence of high-grade reflux were significant risk factors for the future occurrence of lower urinary tract dysfunction. Conclusion It is important to recognize that PUV have consequences not only during childhood or before treatment, but also during or after the treatment period. Long-term assessment and follow-up of upper and lower urinary tract functions after valve ablation is necessary.