[A simulation study of the reliability and accuracy of Cox-TEL method for estimating hazard ratio and difference in proportions for long-term survival data containing cured patients].

OBJECTIVE: To explore the applicable conditions of the Cox-TEL (Cox PH-Taylor expansion adjustment for long-term survival data) method for analysis of survival data that contain cured patients. METHODS: The simulated survival data method based on Weibull distribution was used to simulate and generate the survival data with different cure rates, censored rates, and cure rate differences. The Cox-TEL method was used for analysis of the generated simulation data, and its performance was evaluated by calculating its type Ⅰ error and power. RESULTS: Almost all the type Ⅰ error of the hazard ratios (HRs) obtained by the Cox-TEL method under different conditions were slightly greater than 0.05, and this method showed a good test power for estimating the HRs for data with a large sample size and a large difference in proportions (DPs). For the data of cured patients, the type Ⅰ error of the DPs obtained by the Cox-TEL method was well around 0.05, and its test power was robust in most of the scenarios. CONCLUSION: The Cox-TEL method is effective for analyzing data of uncured patients and obtaining reliable HRs for most of the survival data with a sample size, a low censored rates, and a large difference in cure rates. The method is capable of accurately estimating the DPs regardless of the sample size, censored rates, or the cure rates.

First-in-human feasibility study of the aXess graft (aXess-FIH): 6-Month results.

OBJECTIVE: The creation of an arteriovenous fistula (AVF) is considered the most effective hemodialysis (HD) vascular access. For patients who are not suitable for AVF, arteriovenous grafts (AVGs) are the best access option for chronic HD. However, conventional AVGs are prone to intimal hyperplasia, stenosis, thrombosis, and infection. Xeltis has developed an AVG as a potential alternative to currently available AVGs based on the concept of endogenous tissue restoration. The results of the first 6-month follow-up are presented here. METHODS: The aXess first-in-human (FIH) study [NCT04898153] is a prospective, single-arm, multicenter feasibility study that evaluates the early safety and performance of the aXess Hemodialysis Graft. A total of 20 patients with end-stage renal disease were enrolled across six European investigational sites. RESULTS: At 6-months follow-up, all grafts were patent with primary and secondary patency rates were 80% and 100%, respectively. Three patients required a re-intervention to maintain graft patency, while one re-intervention was required to restore patency. One graft thrombosis and zero infections were reported. CONCLUSION: The expected advantages of the novel aXess Hemodialysis Graft over conventional AVGs would be evaluated by the analysis on long-term safety and effectiveness during the 5-year follow-up of the currently ongoing trial.

Treatment of IgA Nephropathy: A Rapidly Evolving Field.

The pivotal event in the pathophysiology of IgA nephropathy is the binding of circulating IgA-containing immune complexes to mesangial cells, with secondary glomerular and tubulointerstitial inflammation and fibrosis. The paramount difficulty in the management of IgA nephropathy is the heterogeneity in its clinical presentation and prognosis, requiring an individualized treatment approach. Goal-directed supportive care remains the bedrock of therapy for all patients, regardless of risk of progression. Sodium-glucose transporter 2 inhibitors and sparsentan should be integral to contemporary supportive care, particularly in patients with chronic kidney damage. Pending the development of reliable biomarkers, it remains a challenge to identify patients prone to progression due to active disease and most likely to derive a net benefit from immunosuppression. The use of clinical parameters, including the degree of proteinuria, the presence of persistent microscopic hematuria, and the rate of eGFR loss, combined with the mesangial hypercellularity, endocapillary hypercellularity, segmental glomerulosclerosis, tubular atrophy/interstitial fibrosis, crescents score, is currently the best approach. Systemic glucocorticoids are indicated in high-risk patients, but the beneficial effects wane after withdrawal and come at the price of substantial treatment-associated toxicity. Therapies with direct effect on disease pathogenesis are increasingly becoming available. While targeted-release budesonide has garnered the most attention, anti-B-cell strategies and selective complement inhibition will most likely prove their added value. We propose a comprehensive approach that tackles the different targets in the pathophysiology of IgA nephropathy according to their relevance in the individual patient.

Mayo Clinic Consensus Report on Membranous Nephropathy: Proposal for a Novel Classification.

Membranous nephropathy (MN) is a pattern of injury caused by autoantibodies binding to specific target antigens, with accumulation of immune complexes along the subepithelial region of glomerular basement membranes. The past 20 years have brought revolutionary advances in the understanding of MN, particularly via the discovery of novel target antigens and their respective autoantibodies. These discoveries have challenged the traditional classification of MN into primary and secondary forms. At least 14 target antigens have been identified, accounting for 80%-90% of cases of MN. Many of the forms of MN associated with these novel MN target antigens have distinctive clinical and pathologic phenotypes. The Mayo Clinic consensus report on MN proposes a 2-step classification of MN. The first step, when possible, is identification of the target antigen, based on a multistep algorithm and using a combination of serology, staining of the kidney biopsy tissue by immunofluorescence or immunohistochemistry, and/or mass spectrometry methodology. The second step is the search for a potential underlying disease or associated condition, which is particularly relevant when knowledge of the target antigen is available to direct it. The meeting acknowledges that the resources and equipment required to perform the proposed testing may not be generally available. However, the meeting consensus was that the time has come to adopt an antigen-based classification of MN because this approach will allow for accurate and specific MN diagnosis, with significant implications for patient management and targeted treatment.

Mayo Clinic consensus report on membranous nephropathy: proposal for a novel classification.

Membranous nephropathy (MN) is a pattern of injury caused by autoantibodies binding to specific target antigens, with accumulation of immune complexes along the subepithelial region of glomerular basement membranes. The past 20 years have brought revolutionary advances in the understanding of MN, particularly via the discovery of novel target antigens and their respective autoantibodies. These discoveries have challenged the traditional classification of MN into primary and secondary forms. At least 14 target antigens have been identified, accounting for 80%-90% of cases of MN. Many of the forms of MN associated with these novel MN target antigens have distinctive clinical and pathologic phenotypes. The Mayo Clinic consensus report on MN proposes a 2-step classification of MN. The first step, when possible, is identification of the target antigen, based on a multistep algorithm and using a combination of serology, staining of the kidney biopsy tissue by immunofluorescence or immunohistochemistry, and/or mass spectrometry methodology. The second step is the search for a potential underlying disease or associated condition, which is particularly relevant when knowledge of the target antigen is available to direct it. The meeting acknowledges that the resources and equipment required to perform the proposed testing may not be generally available. However, the meeting consensus was that the time has come to adopt an antigen-based classification of MN because this approach will allow for accurate and specific MN diagnosis, with significant implications for patient management and targeted treatment.

[Construction and evaluation of a nomogram for predicting the prognosis of patients with colorectal cancer with peritoneal carcinomatosis treated with cytoreductive surgery plus hyperthermic intraperitoneal chemotherapy].

Objectives: To construct a nomogram incorporating important prognostic factors for predicting the overall survival of patients with colorectal cancer with peritoneal metastases treated with cytoreductive surgery (CRS) plus hyperthermic intraperitoneal chemotherapy (HIPEC), the aim being to accurately predict such patients' survival rates. Methods: This was a retrospective observational study. Relevant clinical and follow-up data of patients with colorectal cancer with peritoneal metastases treated by CRS + HIPEC in the Department of Peritoneal Cancer Surgery, Beijing Shijitan Hospital, Capital Medical University from 2007 January to 2020 December were collected and subjected to Cox proportional regression analysis. All included patients had been diagnosed with peritoneal metastases from colorectal cancer and had no detectable distant metastases to other sites. Patients who had undergone emergency surgery because of obstruction or bleeding, or had other malignant diseases, or could not tolerate treatment because of severe comorbidities of the heart, lungs, liver or kidneys, or had been lost to follow-up, were excluded. Factors studied included: (1) basic clinicopathological characteristics; (2) details of CRS+HIPEC procedures; (3) overall survival rates; and (4) independent factors that influenced overall survival; the aim being to identify independent prognostic factors and use them to construct and validate a nomogram. The evaluation criteria used in this study were as follows. (1) Karnofsky Performance Scale (KPS) scores were used to quantitatively assess the quality of life of the study patients. The lower the score, the worse the patient's condition. (2) A peritoneal cancer index (PCI) was calculated by dividing the abdominal cavity into 13 regions, the highest score for each region being three points. The lower the score, the greater is the value of treatment. (3) Completeness of cytoreduction score (CC), where CC-0 and CC-1 denote complete eradication of tumor cells and CC-2 and CC-3 incomplete reduction of tumor cells. (4) To validate and evaluate the nomogram model, the internal validation cohort was bootstrapped 1000 times from the original data. The accuracy of prediction of the nomogram was evaluated with the consistency coefficient (C-index), and a C-index of 0.70-0.90 suggest that prediction by the model was accurate. Calibration curves were constructed to assess the conformity of predictions: the closer the predicted risk to the standard curve, the better the conformity. Results: The study cohort comprised 240 patients with peritoneal metastases from colorectal cancer who had undergone CRS+HIPEC. There were 104 women and 136 men of median age 52 years (10-79 years) and with a median preoperative KPS score of 90 points. There were 116 patients (48.3%) with PCI≤20 and 124 (51.7%) with PCI>20. Preoperative tumor markers were abnormal in 175 patients (72.9%) and normal in 38 (15.8%). HIPEC lasted 30 minutes in seven patients (2.9%), 60 minutes in 190 (79.2%), 90 minutes in 37 (15.4%), and 120 minutes in six (2.5%). There were 142 patients (59.2%) with CC scores 0-1 and 98 (40.8%) with CC scores 2-3. The incidence of Grade III to V adverse events was 21.7% (52/240). The median follow-up time is 15.3 (0.4-128.7) months. The median overall survival was 18.7 months, and the 1-, 3- and 5-year overall survival rates were 65.8%, 37.2% and 25.7%, respectively. Multivariate analysis showed that KPS score, preoperative tumor markers, CC score, and duration of HIPEC were independent prognostic factors. In the nomogram constructed with the above four variables, the predicted and actual values in the calibration curves for 1, 2 and 3-year survival rates were in good agreement, the C-index being 0.70 (95% CI: 0.65-0.75). Conclusions: Our nomogram, which was constructed with KPS score, preoperative tumor markers, CC score, and duration of HIPEC, accurately predicts the survival probability of patients with peritoneal metastases from colorectal cancer treated with cytoreductive surgery plus hyperthermic intraperitoneal chemotherapy.

Study protocol of a prospective single-arm multicenter clinical study to assess the safety and performance of the aXess hemodialysis graft: The pivotal study.

BACKGROUND: Arteriovenous grafts (AVGs) are used for patients deemed unsuitable for the creation of an autogenous arteriovenous fistula (AVF) or unable to await maturation of the AVF before starting hemodialysis. However, AVGs are prone to infection and thrombosis resulting in low long-term patency rates. The novel aXess Hemodialysis Graft consists of porous polymeric biomaterial allowing the infiltration by cells and the growth of neotissue, while the graft itself is gradually absorbed, ultimately resulting in a fully functional natural blood vessel. The Pivotal Study will examine the long-term effectiveness and safety of the aXess Hemodialysis Graft. METHODS: The Pivotal Study is a prospective, single-arm, multicenter study that will be conducted in 110 subjects with end-stage renal disease who are not deemed suitable for the creation of an autogenous vascular access. The primary efficacy endpoint will be the primary patency rate at 6 months. The primary safety endpoint will be the freedom from device-related serious adverse events at 6 months. The secondary endpoints will include the procedural success rate, time to first cannulation, patency rates, the rate of access-related interventions to maintain patency, the freedom from device-related serious adverse events and the rate of access site infections. Patients will be followed for 60 months. An exploratory Health Economic and Outcomes Research sub-study will determine potential additional benefits of the aXess graft to patients, health care institutions, and reimbursement programs. DISCUSSION: The Pivotal study will examine the long-term performance and safety of the aXess Hemodialysis Graft and compare the outcome measures with historical data obtained with other graft types and autogenous AVFs. Potential advantages may include superior long-term patency rates and lower infection rates versus currently available AVGs and a shorter time to first cannulation compared to an autologous AVF. As such, the aXess Hemodialysis Graft may fulfill an unmet clinical need in the field of hemodialysis access.

Oral Anticoagulation in Patients With Advanced Chronic Kidney Disease and Atrial Fibrillation: Beyond Anticoagulation.

The optimal approach to prevent stroke and systemic embolism in patients with advanced chronic kidney disease (CKD) and atrial fibrillation remains unresolved. We conducted a narrative review to explore areas of uncertainty and opportunities for future research. First, the relationship between atrial fibrillation and stroke is more complex in patients with advanced CKD than in the general population. The currently employed risk stratification tools do not adequately discriminate between patients deriving a net benefit and those suffering a net harm from oral anticoagulation. Anticoagulation initiation should probably be more restrictive than is currently advocated by official guidelines. Recent evidence reveals that the superior benefit-risk profile of non-vitamin K antagonist oral anticoagulants (NOACs) vs vitamin K antagonists (VKAs) observed in the general population and in moderate CKD can be extended to advanced CKD. The NOACs yield better protection against stroke, cause less major bleeding, are associated with less acute kidney injury and a slower decline of CKD, and are associated with a lower incidence of cardiovascular events than VKAs. The VKAs may be harmful in CKD patients, in particular in patients with a high bleeding risk and labile international normalized ratio. The better safety and efficacy of NOACs as opposed to VKAs may be particularly evident in advanced CKD as a result of better on-target anticoagulation with NOACs, harmful off-target vascular effects of VKAs, and beneficial off-target vascular effects of NOACs. The intrinsic vasculoprotective effects of NOACs are supported by animal experimental evidence as well as by findings of large clinical trials and may result in use of NOACs beyond their anticoagulant properties.

[Comparison of prediction ability of two extended Cox models in nonlinear survival data analysis].

OBJECTIVE: To compare the predictive ability of two extended Cox models in nonlinear survival data analysis. METHODS: Through Monte Carlo simulation and empirical study and with the conventional Cox Proportional Hazards model and Random Survival Forests as the reference models, we compared restricted cubic spline Cox model (Cox_RCS) and DeepSurv neural network Cox model (Cox_DNN) for their prediction ability in nonlinear survival data analysis. Concordance index was used to evaluate the differentiation of the prediction results (a larger concordance index indicates a better prediction ability of the model). Integrated Brier Score was used to evaluate the calibration degree of the prediction (a smaller index indicates a better prediction ability). RESULTS: For data that met requirement of the proportion risk, the Cox_RCS model had the best prediction ability regardless of the sample size or deletion rate. For data that failed to meet the proportion risk, the prediction ability of Cox_DNN was optimal for a large sample size (≥500) with a low deletion (< 40%); the prediction ability of Cox_RCS was superior to those of other models in all other scenarios. For example data, the Cox_RCS model showed the best performance. CONCLUSION: In analysis of nonlinear low maintenance data, Cox_RCS and Cox_DNN have their respective advantages and disadvantages in prediction. The conventional survival analysis methods are not inferior to machine learning or deep learning methods under certain conditions.

[Comparison of 7 methods for sample size determination based on confidence interval estimation for a single proportion].

OBJECTIVE: To compare different methods for calculating sample size based on confidence interval estimation for a single proportion with different event incidences and precisions. METHODS: We compared 7 methods, namely Wald, AgrestiCoull add z2, Agresti-Coull add 4, Wilson Score, Clopper-Pearson, Mid-p, and Jefferys, for confidence interval estimation for a single proportion. The sample size was calculated using the search method with different parameter settings (proportion of specified events and half width of the confidence interval [ω=0.05, 0.1]). With Monte Carlo simulation, the estimated sample size was used to simulate and compare the width of the confidence interval, the coverage of the confidence interval and the ratio of the noncoverage probability. RESULTS: For a high accuracy requirement (ω =0.05), the Mid-p method and Clopper Pearson method performed better when the incidence of events was low (P < 0.15). In other settings, the performance of the 7 methods did not differ significantly except for a poor symmetry of the Wald method. In the setting of ω=0.1 with a very low p (0.01-0.05), failure of iteration occurred with nearly all the methods except for the Clopper-Pearson method. CONCLUSION: Different sample size determination methods based on confidence interval estimation should be selected for single proportions with different parameter settings.

Clinicopathological characteristics and disease chronicity in native kidney biopsies in Flanders.

Background: The Flemish Collaborative Glomerulonephritis Group (FCGG) registry provides complete population data on kidney disease epidemiology in the region of Flanders (Belgium), as it captures all native kidney biopsies performed in its population of 6.5 million inhabitants. Methods: From 2017 until 2019, 2054 adult kidney biopsies were included from 26 nephrology centers (one biopsy per patient). Data on nephrotic and nephritic syndrome were available in 1992 and 2026 biopsies, respectively. In a subgroup of 898 biopsies containing ≥10 glomeruli from 2018 to 2019, disease chronicity was graded using the Mayo Clinic Chronicity Score (MCCS). The association between clinical variables and MCCS was determined using simple and multiple linear regression models. Results: Nephrotic syndrome (present in 378 patients, 19.0%) was most frequently caused by minimal change disease in younger patients (18-44 years), membranous nephropathy in older patients (45-74 years) and amyloidosis in the elderly (>75 years). Nephritic syndrome (present in 421 patients, 20.8%) was most frequently caused by immunoglobulin A nephropathy (IgAN) in younger patients (18-64 years) and ANCA-associated vasculitis (AAV) in older patients (>64 years). AAV and IgAN were the most frequent underlying diagnoses in biopsies in which crescents were identified. In multivariable analysis, acute and chronic kidney disease and diagnoses of diabetic kidney disease, nephrosclerosis and hyperoxaluria/hypercalcemic nephropathy were associated with the highest MCCS increases. Conclusions: The FCGG registry validates data from previous Western European registries and provides a snapshot of disease chronicity in the whole biopsied Flemish population.

Influence of dietary crude protein on growth performance and apparent and standardized ileal digestibility of amino acids in corn-soybean meal-based diets fed to broilers.

This study aimed to examine the influence of dietary CP on the apparent ileal digestibility (AID) and standardized ileal digestibility (SID) of amino acids (AA) and test the additivity of AA digestibility in corn-soybean meal-based diets fed to broilers. Six experimental diets comprising a nitrogen-free diet and five corn-soybean meal-based diets containing 6.0%, 9.5%, 13.0%, 16.5%, and 20.0% CP were prepared. Increments in CP and AA concentrations were achieved by increasing the inclusion rate of corn and soybean meal at the expense of cornstarch. All diets contained 0.5% chromic oxide, which was included as an indigestible index. A total of 960 Ross 308 male broilers 19-day-old male broilers (Ross 308), with a mean BW of 628 g (SD = 58.0), were allocated to six dietary treatment groups in a randomized complete block design, with each treatment group have eight replicate cages and 20 birds per cage. All birds were fed the experimental diets for 4 days. On d 23, individual BW and feed intake were recorded, followed by collection of ileal digesta samples from the distal ileum. Regarding growth, the final BW, weight gain, feed intake, and gain to feed ratio increased linearly (P < 0.001) as dietary CP concentrations increased. With the increase in dietary CP concentrations from 6.0% to 20.0%, the AID of all AA, except Arg, increased linearly (P < 0.05). However, the SID of all AA, except Arg, Cys, and Pro, remained unaffected by CP concentrations in the diets. This study indicated that dietary CP concentrations from 6.0% to 20.0% have an effect on the growth performance of birds and the AID of most AA; however, the SID of most AA was not affected by dietary CP concentrations in the corn-soybean meal-based diets. In conclusion, the SID of AA is more additive than the AID of AA in poultry diets containing CP in the range of 6.0% to 20.0%.

[Medical costs of brucellosis patients in Datong of Shanxi province, 2017-2019].

Objective: To explore the medical costs and influencing factors of patients diagnosed with Brucellosis in Datong of Shanxi province. Methods: Information on demographics, medical visits, and costs of patients diagnosed with Brucellosis between January 1, 2017, and December 31, 2019, were collected. Health care utilization and medical costs were analyzed from different genders, age groups, underlying diseases, clinical stages, and comorbidities. Results: A total of 2 289 patients (1 715 outpatient and 574 inpatient cases) were included in the analysis. 72.0% (1 649/2 289) were male, with an average age of (49.6±15.5) years; age between 45-59 years was the dominant group (36.2%,829/2 289). The mean age of inpatients (51.4±16.0) was higher than that of outpatients (49.0±15.2)(Z=-4.01, P<0.001). The average number of outpatient visits per outpatient was (1.6±1.5) times. The duration of hospitalization was (14.6±9.9) and (20.8±11.4) days for patients with central nervous system complications and (16.6±9.5) days for vascular system complications. Of the inpatients, 51.0% (293/574) had underlying diseases, and 30.3% (174/574) had endocrine and metabolic diseases. 54.0% (310/574) of inpatients were diagnosed with acute Brucellosis, and 46.0% (264/574) were diagnosed with chronic Brucellosis. A total of 64.3% (369/574) of inpatients had complications, 30.3% (174/574) of digestive system complications, followed by skeletal system complications (29.1%, 167/574). Among outpatients, age significantly affected medical costs (P<0.001). For inpatients, age and complications and treatment effect were influential factors (P<0.05). Patients with the combined skeletal system and central nervous system complications had significantly higher medical costs (P<0.001). Conclusions: The medical costs for outpatient cases of Brucellosis were moderate. However, the economic burden was higher for inpatients, especially those with skeletal and neurological complications. Early detection, diagnosis, and treatment of cases were essential to avoid chronic Brucellosis and its complications and reduce medical costs.

Effects of corn particle size on growth performance, gastrointestinal development, carcass indices and intestinal microbiota of broilers.

This experiment was conducted to investigate the effects of different corn particle sizes on growth performance, gastrointestinal development, carcass processing yields and intestinal microbiota of caged broilers. One-day-old Ross 308 broilers were randomly divided into 8 treatments with 10 replicates per treatment and 30 birds per replicate pen. The experiment lasted 37 d. Feed and water were provided ad libitum. The results showed as follows: birds fed diets with the FG corn between d 1 and 13 and CG corn between d14 to 37 had increased body weight, daily gain, and feed intake (P < 0.05). Birds fed diets with CG corn between d 24 to 37 had a heavier relative weight of gizzard at d 38 (P < 0.05). Birds fed diets with FG corn from d 1 to 13 and the CG corn from d 14 to 37 had a higher carcass yield and a relative thigh weight at d 38 (P < 0.05). The intestinal microbiota was significantly affected by different corn particle sizes. The relative abundance of Lactobacillaceae was significantly decreased, whereas that of Peptostreptococcaceae was increased (P < 0.05) in birds fed with the CG corn between d1 to 37. The relative abundance of Acinetobacter was significantly increased in birds fed the FG corn between d1 to 37 (P < 0.05). In conclusion, the use of FG corn in the starter phase and CG corn in the grower and finisher phases was beneficial to growth performance, gastrointestinal development and intestinal microbial structure of broilers reared in cages.

Immune Senescence Markers Predict the Cellular Immune Response to BNT162b2 Vaccination in Hemodialysis Patients.

Background: Chronic kidney disease is associated with increased risk of frailty and accelerated immune senescence, potentially affecting the immune response to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccination. Methods: Humoral and cellular responses against the spike protein of SARS-CoV-2 were determined in 189 COVID-naive hemodialysis patients at week 4 and 8 after vaccination with 2 doses of BNT162b2. Frailty indicators and immune senescence markers were determined at baseline to identify predictors of the immune response. Results: Controlling for age, activities of daily living (ADLs), instrumental ADLs, walking pace, and the clinical frailty score correlated negatively and hand grip strength positively with the humoral response. Controlling for age, the proportions of memory CD4+ T cells, memory CD8+ T cells, CD28null T cells, and CD57+CD8+ T cells correlated negatively with the humoral response, whereas the proportions of memory CD4+ T cells and CD28null T cells correlated negatively and the CD4/CD8 ratio positively with the cellular response. In a multivariate model, only the proportions of memory CD4+ T cells and CD28null T cells independently predicted the cellular response. Conclusions: Markers of immune senescence, but not frailty indicators, independently predict the cellular immune response after vaccination in hemodialysis patients, overruling the effect of chronological age.

[Guillain-Barre syndrome associated with COVID-19]. / Sindrom Giiena­Barre, assotsiirovannyi s COVID-19.

This paper reports two cases of Guillain-Barre syndrome associated with coronavirus infection COVID-19. The clinical symptoms and neurological status of patients, the data of the additional examination and the features of the prescribed therapy are described in detail. The issue of the tropicity of the SARS-CoV-2 virus to human nervous tissue and its possible ways of affecting the peripheral nervous system is discussed.

Epidemiology of native kidney disease in Flanders: results from the FCGG kidney biopsy registry.

Background: The Flemish Collaborative Glomerulonephritis Group (FCGG) registry is the first population-based native kidney biopsy registry in Flanders, Belgium. In this first analysis, we report on patient demographics, frequency distribution and incidence rate of biopsied kidney disease in adults in Flanders. Methods: From January 2017 to December 2019, a total of 2054 adult first native kidney biopsies were included. A 'double diagnostic coding' strategy was used, in which every biopsy sample received a histopathological and final clinical diagnosis. Frequency distribution and incidence rate of both diagnoses were reported and compared with other European registries. Results: The median age at biopsy was 61.1 years (interquartile range, 46.1-71.7); male patients were more prevalent (62.1%) and biopsy incidence rate was 129.3 per million persons per year. Immunoglobulin A nephropathy was the most frequently diagnosed kidney disease (355 biopsies, 17.3% of total) with a similar frequency as in previously published European registries. The frequency of tubulointerstitial nephritis (220 biopsies, 10.7%) and diabetic kidney disease (154 biopsies, 7.5%) was remarkably higher, which may be attributed to changes in disease incidence as well as biopsy practices. Discordances between histopathological and final clinical diagnoses were noted and indicate areas for improvement in diagnostic coding systems. Conclusions: The FCGG registry, with its 'double diagnostic coding' strategy, provides useful population-based epidemiological data on a large Western European population and allows subgroup selection for future research.

Acute glomerulonephritis.

Glomerulonephritis is a heterogeneous group of disorders that present with a combination of haematuria, proteinuria, hypertension, and reduction in kidney function to a variable degree. Acute presentation with full blown nephritic syndrome or rapidly progressive glomerulonephritis is uncommon and is mainly restricted to patients with post-infectious glomerulonephritis, anti-neutrophil cytoplasmic antibodies-associated vasculitis, and anti-glomerular basement membrane disease. Most frequently, patients present with asymptomatic haematuria and proteinuria with or without reduced kidney function. All glomerulonephritis disorders can show periods of exacerbation, but disease flairs characteristically occur in patients with IgA nephropathy or C3 glomerulopathy. The gold standard for the diagnosis of a glomerulonephritis is a kidney biopsy, with a hallmark glomerular inflammation that translates into various histopathological patterns depending on the location and severity of the glomerular injury. Traditionally, glomerulonephritis was classified on the basis of the different histopathological patterns of injury. In the last few years, substantial progress has been made in unravelling the underlying causes and pathogenetic mechanisms of glomerulonephritis and a causal approach to the classification of glomerulonephritis is now favoured over a pattern-based approach. As such, glomerulonephritis can be broadly classified as immune-complex glomerulonephritis (including infection-related glomerulonephritis, IgA nephropathy, lupus nephritis, and cryoglobulinaemic glomerulonephritis), anti-neutrophil cytoplasmic antibodies-associated (pauci-immune) glomerulonephritis, anti-glomerular basement membrane glomerulonephritis, C3 glomerulopathy, and monoclonal immunoglobulin-associated glomerulonephritis. We provide an overview of the clinical presentation, pathology, and the current therapeutic approach of the main representative disorders in the spectrum of glomerulonephritis.