Predicting outcome in acute interstitial nephritis: a case-series examining the importance of histological parameters.

AIMS: The clinical significance of common histological parameters in acute interstitial nephritis (AIN) is uncertain. We aimed to evaluate the utility of histology in predicting clinical outcomes in patients with AIN. METHODS AND RESULTS: Adult renal biopsies yielding a diagnosis of AIN between 2000 and 2015 were re-examined. Patients were divided into groups based on: (i) the percentage of non-fibrotic cortex containing inflammation (NFI score) (NFI-1 = 0-24%; NFI-2 = 25-74%; NFI-3 = 75-100%) and (ii) the percentage of cortex containing tubular atrophy (TA score) (TA1 = 0-9%; TA2 = 10-24%; TA3 = 25-100%). The primary outcome was a composite of ≥50% reduction in serum creatinine (sCr) or an estimated glomerular filtration rate (eGFR) > 60 ml/min/1.73 m2 1 year post-biopsy. From a total of 2817 native renal biopsies, there were 120 patients with AIN and adequate data for analysis. Of these, 66 (56%) achieved the primary outcome. On univariable logistic regression, NFI-3 was associated with a 16 times increased likelihood of achieving the primary outcome compared to NFI-1 [odds ratio (OR) = 16, 95% confidence interval (CI) = 5.2-50)]. In contrast, TA3 was associated with a 90% reduced likelihood of achieving the primary outcome compared to TA1 (OR = 0.10, 95% CI = 0.0-0.3). Maximal clinical utility was achieved by combining TA and NFI into a single prognostic 'TANFI' score, which had an independent predictive effect on the primary outcome in a multivariable regression model consisting of age, sex, baseline sCr and identified drug cause. CONCLUSIONS: In patients with biopsy-proven AIN, a lower percentage of cortical tubular atrophy and, paradoxically, a higher percentage of inflammation in non-fibrosed cortex were associated with an increased likelihood of a positive clinical outcome.

Proteinase-3 and myeloperoxidase serotype in relation to demographic factors and geographic distribution in anti-neutrophil cytoplasmic antibody-associated glomerulonephritis.

Background: In anti-neutrophil cytoplasmic antibody (ANCA)-associated glomerulonephritis, antigen specificity varies between myeloperoxidase (MPO) and proteinase 3 (PR3). This has been reported to vary in relation to age, gender, geography and extrarenal manifestations. However, studies are difficult to compare as criteria for inclusion vary. The aim of this study was to investigate the relationship between ANCA serotype, latitude, ultraviolet (UV) radiation levels, age, gender and renal function at diagnosis in a large study with uniform inclusion criteria. Methods: Patients with biopsy-proven ANCA-associated glomerulonephritis were identified from regional or nationwide registries in 14 centres in Norway, Sweden, the UK, the Czech Republic, Croatia, Italy and the USA during the period 2000-13. UV radiation levels for 2000-13 in Europe were obtained from the Swedish Meteorological and Hydrological Institute. Results: A total of 1408 patients (45.2% PR3-ANCA) were included in the study. In univariable analysis, PR3-ANCA was significantly associated with male gender {odds ratio [OR] 2.12 [95% confidence interval (CI) 1.71-2.62]}, younger age [OR per year 0.97 (95% CI 0.96-0.98)] and higher glomerular filtration rate [OR per mL/min 1.01 (95% CI 1.01-1.02); P < 0.001] at diagnosis but not with latitude or UV radiation. In multivariable logistic regression analysis, latitude and UV radiation also became significant, with higher odds for PR3-ANCA positivity at northern latitudes/lower UV radiation levels. However, the latitudinal difference in MPO:PR3 ratio is smaller than differences previously reported concerning microscopic polyangiitis and granulomatosis with polyangiitis. Conclusions: The ratio between PR3-ANCA and MPO-ANCA varies in glomerulonephritis with respect to age, gender, renal function and geographic latitude/UV radiation levels.

Obesity is not associated with progression to end stage renal disease in patients with biopsy-proven glomerular diseases.

BACKGROUND: Body mass index (BMI) is associated with renal disease progression in unspecified CKD. The relationship between BMI and primary glomerular disease (GN) may be more complex. We aimed to evaluate the association between BMI and renal disease progression in patients with primary glomerular disease (GN). METHODS: This was a single-centre retrospective cohort study performed in adult patients with biopsy-proven primary GN (excluding minimal change disease) from January 2000 to December 2015, with follow-up data until June 2017. BMI at time of biopsy was categorised as ≤25 kg/m2, > 25 to ≤30 kg/m2 and > 30 kg/m2. We used univariate and multivariate survival analyses to evaluate factors associated with progression to a composite endpoint of stage 5 CKD or renal replacement therapy (Major Adverse Renal Event - MARE) censoring for competing risk of death using Fine and Gray subdistribution hazards model. RESULTS: We included 560 patients with biopsy-proven primary GN and available BMI data: 66.1% were male with median age 54.8 (IQR 41.1-66.2) years and BMI 28.2 (IQR 24.9-32.1) kg/m2. Those with BMI 25-30 kg/m2 (n = 210) and with BMI > 30 kg/m2 (n = 207) were older (p = 0.007) with higher systolic and diastolic blood pressures (p = 0.02 and 0.004 respectively) than those with BMI < 25 kg/m2 (n = 132). There was a greater proportion of focal segmental glomerulosclerosis in those with higher BMI (3.9% in BMI < 25 kg/m2, 7.9% in BMI 25-30 kg/m2 and 10.7% in BMI > 30 kg/m2 of biopsies (p = 0.01)), but similar proportions of other GN diagnoses across BMI groups. Baseline eGFR (p = 0.40) and uPCR (p = 0.17) were similar across BMI groups. There was no interaction between BMI and time to MARE (log-rank p = 0.98) or death (log-rank p = 0.42). Censoring for competing risk of death, factors associated with progression to MARE were: younger age, lower baseline eGFR and higher uPCR, but not BMI (SHR 0.99, 95%CI 0.97-1.01, p = 0.31) nor blood pressure or GN diagnosis. CONCLUSION: BMI was not associated with progression to MARE in this patient cohort with primary GN. Efforts should be directed to managing other known risk factors for CKD progression.

Factors influencing withdrawal from dialysis: a national registry study.

BACKGROUND: Dialysis withdrawal is the third most common cause of death in patients receiving dialysis for established renal failure (ERF) in Scotland. We describe incidence, risk factors and themes influencing decision-making in a national renal registry. METHODS: Details of deaths in those receiving renal replacement therapy (RRT) for ERF in Scotland are reported to the Scottish Renal Registry via a unique mortality report. We extracted patient demographics and comorbidity, cause and location of death, duration of RRT and pertinent free text comments from 1 January 2008 to 31 December 2014. Withdrawal incidence was calculated and logistic regression used to identify significantly influential variables. Themes emerging from clinician comments were tabulated for descriptive purposes. RESULTS: There were 2596 deaths; median age at death was 68 [interquartile range (IQR) 58, 76] years, 41.5% were female. Median duration on RRT was 1110 (IQR 417, 2151) days. Dialysis withdrawal was the primary cause of death in 497 (19.1%) patients and withdrawal contributed to death in a further 442 cases (17.0%). The incidence was 41 episodes per 1000 patient-years. Regression analysis revealed increasing age, female sex and prior cerebrovascular disease were associated with dialysis withdrawal as a primary cause of death. Conversely, interstitial renal disease, angiographically proven ischaemic heart disease, valvular heart disease and malignancy were negatively associated. Analysis of free text comments revealed common themes, portraying an image of physical and psychological decline accelerated by acute illnesses. CONCLUSIONS: Death following dialysis withdrawal is common. Factors important to physical independence-prior cerebrovascular disease and increasing age-are associated with withdrawal. When combined with clinician comments this study provides an insight into the clinical decline affecting patients and the complexity of this decision. Early recognition of those likely to withdraw may improve end of life care.

Teaching percutaneous renal biopsy using unfixed human cadavers.

BACKGROUND: Percutaneous renal biopsy (PRB) is an important diagnostic procedure. Despite advances in its safety profile there remains a small but significant risk of bleeding complications. Traditionally, operators train to perform PRB through tutor instruction and directly supervised PRB attempts on real patients. We describe an approach to teaching operators to perform PRB using cadaveric simulation. METHODS: We devised a full day course hosted in the Clinical Anatomy Skills Centre, with places for nine candidates. Course faculty consisted of two Consultant Nephrologists, two Nephrology trainees experienced in PRB, and one Radiologist. Classroom instruction included discussion of PRB indications, risk minimisation, and management of complications. Two faculty members acted as models for the demonstration of kidney localisation using real-time ultrasound scanning. PRB was demonstrated using a cadaveric model, and candidates then practised PRB using each cadaver model. RESULTS: Written candidate feedback was universally positive. Faculty considered the cadaveric model a realistic representation of live patients, while the use of multiple cadavers introduced anatomical variation. CONCLUSIONS: Our model facilitates safe simulation of a high risk procedure. This might reduce serious harm associated with PRB and improve patient safety, benefiting trainee operators and patients alike.

The incidence of biopsy-proven IgA nephropathy is associated with multiple socioeconomic deprivation.

Chronic kidney disease is more common in areas of socioeconomic deprivation, but the relationship with the incidence and diagnosis of biopsy-proven renal disease is unknown. In order to study this, all consecutive adult patients undergoing renal biopsy in West and Central Scotland over an 11-year period were prospectively analyzed for demographics, indication, and histologic diagnosis. Using the Scottish Index of Multiple Deprivation, 1555 eligible patients were separated into quintiles of socioeconomic deprivation according to postcode. Patients in the most deprived quintile were significantly more likely to undergo biopsy compared with patients from less deprived areas (109.5 compared to 95.9 per million population/year). Biopsy indications were significantly more likely to be nephrotic syndrome, or significant proteinuria without renal impairment. Patients in the most deprived quintile were significantly more likely to have glomerulonephritis. There was a significant twofold increase in the diagnosis of IgA nephropathy in the patients residing in the most compared with the least deprived postcodes not explained by the demographics of the underlying population. Thus, patients from areas of socioeconomic deprivation in West and Central Scotland are significantly more likely to undergo native renal biopsy and have a higher prevalence of IgA nephropathy.

How safe is renal replacement therapy? A national study of mortality and adverse events contributing to the death of renal replacement therapy recipients.

BACKGROUND: Patients receiving treatment with renal replacement therapy (RRT) have high mortality, and ensuring patient safety in this population is difficult. We aimed to estimate the incidence and nature of medical adverse events contributing to the death of patients being treated with RRT. METHODS: This population registry-based retrospective case review study included all patients being treated with RRT for established renal failure in Scotland and who died between 1 January 2008 and 30 June 2011. Deaths were reviewed by consultant nephrologists using a structured questionnaire to identify factors contributing to death occurring in both the inpatient and outpatient setting. Reviewers were able to use any information source deemed relevant, including paper and electronic clinical records, mortality and morbidity meetings and procurator fiscal (Scottish coroner) investigations. Deaths occurring in 2008 and 2009 where avoidable factors were identified that may have or did lead to death of a patient were subject to further review and root cause analysis, in order to identify recurrent themes. RESULTS: Of 1551 deaths in the study period, 1357 were reviewed (87.5%). Cumulative RRT exposure in the cohort was 2.78 million person-days. RRT complications were the primary cause of death in 28 (2.1%). Health-care-associated infection had contributed to 9.6% of all deaths. In 3.5% of deaths, factors were identified which may have or did contribute to death. These were both organizational and human error related and were largely due to five main causes: management of hyperkalaemia, prescribing, out of hours care, infection and haemodialysis vascular access. CONCLUSIONS: Adverse events contributing to death in RRT recipients mainly relate to the everyday management of common medical problems and not the technical aspects of RRT. Efforts to avoid harm in this population should address these ubiquitous causes of harm.

Outcomes in ANCA-Associated Vasculitis in Scotland: Validation of the Renal Risk Score in a Complete National Cohort.

Introduction: Antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) causes autoimmune-mediated inflammation of small blood vessels in multiple organs, including the kidneys. The ability to accurately predict kidney outcomes would enable a more personalized therapeutic approach. Methods: We used our national renal biopsy registry to validate the ability of ANCA Renal Risk Score (ARRS) to predict end-stage kidney disease (ESKD) for individual patients. This score uses histopathological and biochemical data to stratify patients as high, medium, or low risk for developing ESKD. Results: A total of 288 patients were eligible for inclusion in the study (low risk n = 144, medium risk n = 122, high risk n = 12). Using adjusted Cox proportional hazard models with the low-risk group as reference, we show that outcome differs between the categories: high-risk hazard ratio (HR) 16.69 (2.91-95.81, P = 0.002); medium risk HR 4.14 (1.07-16.01, P = 0.039). Incremental multivariable-adjusted Cox proportional hazards models demonstrated that adding ARRS to a model adjusted for multiple clinical parameters enhanced predictive discrimination (basic model C-statistic 0.864 [95% CI 0.813-0.914], basic model plus ARRS C-statistic 0.877 [95% CI 0.823-0.931]; P <0.01). Conclusion: The ARRS better discriminates risk of ESKD in AAV and offers clinicians more prognostic information than the use of standard biochemical and clinical measures alone. This is the first time the ARRS has been validated in a national cohort. The proportion of patients with high-risk scores is lower in our cohort compared to others and should be noted as a limitation of this study.

Fractional excretions of albumin and IgG are the best predictors of progression in primary glomerulonephritis.

BACKGROUND: Proteinuria is the most sensitive predictor of development of progressive renal insufficiency, with increasing focus on the composition of proteinuria, particularly high molecular weight proteins such as immunoglobulin G (IgG) (molecular weight 150 kDa). Differing methods of assessing excretion of proteinuria molecules have limited interpretation of results. We aimed to assess the utility of available indices of IgG, total proteinuria and albumin excretions as predictors of chronic kidney disease (CKD) progression in patients with primary glomerulonephritis. METHODS: We recruited 97 patients with primary glomerulonephritis and measured 24-h urinary protein excretion, 24-h urinary albumin excretion, selectivity index, albumin:creatinine ratio, urinary IgG:creatinine ratio, fractional excretion of albumin (FE Alb) and fractional excretion of IgG (FE IgG) at baseline. The composite endpoint was developing stage 5 CKD, requiring RRT or death. Receiver operating characteristics curve analysis was used to assess the value of each measure in predicting outcome. From this analysis, high- and low-risk patient groups according to each measure were established. These were then tested using Kaplan-Meier and Cox survival analysis. RESULTS: During a median follow-up of 7.07 years, 23 patients developed the primary endpoint. FE IgG and FE Alb were the most sensitive predictive tests. The hazard ratios (HR) of developing the primary endpoint using FE IgG [HR 37.1 (95% CI 8.6-158.8)] and FE Alb [HR 35.2 (95% CI 8.2-150.8)] cut-offs were double those using the other measures. CONCLUSIONS: FE IgG and FE Alb are superior to conventional measures of proteinuria in predicting outcome in patients with primary glomerulonephritis, possibly because they are more accurate indicators of impairment of glomerular permselectivity. FE Alb should be used, in conjunction with other measures of proteinuria, in future studies of prediction of CKD progression.

ANCA-associated renal vasculitis is associated with rurality but not seasonality or deprivation in a complete national cohort study.

BACKGROUND: Small studies suggest an association between ANCA-associated vasculitis (AAV) incidence and rurality, seasonality and socioeconomic deprivation. We examined the incidence of kidney biopsy-proven AAV and its relationship with these factors in the adult Scottish population. METHODS: Using the Scottish Renal Biopsy Registry, all adult native kidney biopsies performed between 2014 and 2018 with a diagnosis of granulomatosis with polyangiitis (GPA) or microscopic polyangiitis (MPA) were identified. The Scottish Government Urban Rural Classification was used for rurality analysis. Seasons were defined as autumn (September-November), winter (December-February), spring (March-May) and summer (June-August). Patients were separated into quintiles of socioeconomic deprivation using the validated Scottish Index of Multiple Deprivation and incidence standardised to age. Estimated glomerular filtration rate and urine protein:creatinine ratio at time of biopsy were used to assess disease severity. RESULTS: 339 cases of renal AAV were identified, of which 62% had MPA and 38% had GPA diagnosis. AAV incidence was 15.1 per million population per year (pmp/year). Mean age was 66 years and 54% were female. Incidence of GPA (but not MPA) was positively associated with rurality (5.2, 8.4 and 9.1 pmp/year in 'urban', 'accessible remote' and 'rural remote' areas, respectively; p=0.04). The age-standardised incidence ratio was similar across all quintiles of deprivation (p=ns). CONCLUSIONS: Seasonality and disease severity did not vary across AAV study groups. In this complete national cohort study, we observed a positive association between kidney biopsy-proven GPA and rurality.

Hematuria Is Associated with More Severe Acute Tubulointerstitial Nephritis.

Acute tubulointerstitial nephritis (ATIN) is a common cause of acute kidney injury. Although haematuria is a risk factor for the development of renal disease, no previous study has analyzed the significance of haematuria in ATIN. Retrospective, observational analysis of 110 patients with biopsy-proven ATIN was conducted. Results: Haematuria was present in 66 (60%) ATIN patients. A higher percentage of ATIN patients with haematuria had proteinuria than patients without haematuria (89.4% vs. 59.1%, p = 0.001) with significantly higher levels of proteinuria (median (interquartile range) protein:creatinine ratio 902.70 (513-1492) vs. 341.00 (177-734) mg/g, p <0.001). Moreover, those patients with more haematuria intensity had a higher urinary protein:creatinine ratio (1352.65 (665-2292) vs. 849.60 (562-1155) mg/g, p = 0.02). Those patients with higher proteinuria were more likely to need renal replacement therapy (22.7 vs. 0%, p = 0.03) and to suffer relapse (4 vs. 0%, p = 0.03). At the end of follow up, haematuric ATIN patients had higher serum creatinine levels (3.19 ± 2.91 vs. 1.91 ± 1.17 mg/dL, p = 0.007), and a trend towards a higher need for acute dialysis (7 vs. 1%, p = 0.09) and renal replacement therapy (12.1 vs. 2.3%, p = 0.12). Haematuria is common in ATIN and it is associated with worse renal function outcomes.

The Oxford classification of IgA nephropathy: pathology definitions, correlations, and reproducibility.

Pathological classifications in current use for the assessment of glomerular disease have been typically opinion-based and built on the expert assumptions of renal pathologists about lesions historically thought to be relevant to prognosis. Here we develop a unique approach for the pathological classification of a glomerular disease, IgA nephropathy, in which renal pathologists first undertook extensive iterative work to define pathologic variables with acceptable inter-observer reproducibility. Where groups of such features closely correlated, variables were further selected on the basis of least susceptibility to sampling error and ease of scoring in routine practice. This process identified six pathologic variables that could then be used to interrogate prognostic significance independent of the clinical data in IgA nephropathy (described in the accompanying article). These variables were (1) mesangial cellularity score; percentage of glomeruli showing (2) segmental sclerosis, (3) endocapillary hypercellularity, or (4) cellular/fibrocellular crescents; (5) percentage of interstitial fibrosis/tubular atrophy; and finally (6) arteriosclerosis score. Results for interobserver reproducibility of individual pathological features are likely applicable to other glomerulonephritides, but it is not known if the correlations between variables depend on the specific type of glomerular pathobiology. Variables identified in this study withstood rigorous pathology review and statistical testing and we recommend that they become a necessary part of pathology reports for IgA nephropathy. Our methodology, translating a strong evidence-based dataset into a working format, is a model for developing classifications of other types of renal disease.

The Oxford classification of IgA nephropathy: rationale, clinicopathological correlations, and classification.

IgA nephropathy is the most common glomerular disease worldwide, yet there is no international consensus for its pathological or clinical classification. Here a new classification for IgA nephropathy is presented by an international consensus working group. The goal of this new system was to identify specific pathological features that more accurately predict risk of progression of renal disease in IgA nephropathy, thus enabling both clinicians and pathologists to improve individual patient prognostication. In a retrospective analysis, sequential clinical data were obtained on 265 adults and children with IgA nephropathy who were followed for a median of 5 years. Renal biopsies from all patients were scored by pathologists blinded to the clinical data for pathological variables identified as reproducible by an iterative process. Four of these variables: (1) the mesangial hypercellularity score, (2) segmental glomerulosclerosis, (3) endocapillary hypercellularity, and (4) tubular atrophy/interstitial fibrosis were subsequently shown to have independent value in predicting renal outcome. These specific pathological features withstood rigorous statistical analysis even after taking into account all clinical indicators available at the time of biopsy as well as during follow-up. The features have prognostic significance and we recommended they be taken into account for predicting outcome independent of the clinical features both at the time of presentation and during follow-up. The value of crescents was not addressed due to their low prevalence in the enrolled cohort.

Centre variation in incidence, indication and diagnosis of adult native renal biopsy in Scotland.

BACKGROUND: UK native renal biopsy incidence is unknown. Biopsy registries in other countries indicate that the incidence of renal biopsy varies widely. Indications for renal biopsy are largely opinion based. METHODS: The Scottish Renal Biopsy Registry aimed to analyse the incidence of native renal biopsy in Scotland and examine indications and diagnoses obtained where practice varied widely. RESULTS: Consecutive native adult renal biopsies performed in eight of the nine Scottish regions that include 82.4% of the population between 2002 and 2006 were examined. A total of 2480 native renal biopsies were performed equating 126.3 biopsies per million population per year (PMP/year). A total of 56.9% of patients were male, mean age 55.6 years (SD 1.3). The centres varied widely, from a lowest mean annual incidence of 65.8 PMP/year in Fife to the highest of 170.7 PMP/year in Tayside. The prospectively recorded indications and diagnoses were compared between Greater Glasgow, Clyde and Forth Valley (GC&FV) (population 1.56 million, 101.6 biopsies PMP/year) and Tayside (population 0.39 million, 177.4 biopsies PMP/year). Differing incidence of renal biopsy in these regions was mainly explained by patients with proteinuria and preserved renal function in the absence of nephrotic syndrome (19.2 PMP/year in GC&FV versus 60.8 PMP/year in Tayside), probably due to variation in nephrologists' opinion about the utility of biopsy for this indication. Tayside diagnosed more primary glomerulopathies, diabetic nephropathy and chronic ischaemia than GC&FV. CONCLUSIONS: We have demonstrated wide regional variability in incidence of native renal biopsy within a single country, with analysis suggesting that this is mainly explained by uncertainty about the utility of renal biopsy for patients with proteinuria and preserved renal function. Further studies are required to determine the value of renal biopsy in this setting.

Assessment of active tubulointerstitial nephritis in non-scarred renal cortex improves prediction of renal outcomes in patients with IgA nephropathy.

BACKGROUND: The addition of tubulointerstitial inflammation to the existing pathological classification of IgA nephropathy (IgAN) is appealing but was previously precluded due to reportedly wide inter-observer variability. We report a novel method to score percentage of non-atrophic renal cortex containing active tubulointerstitial inflammation (ATIN) in patients with IgAN and assess its utility to predict clinical outcomes. METHODS: All adult patients with a native renal biopsy diagnosis of IgAN between 2010 and 2015 in a unit serving 1.5 million people were identified. Baseline characteristics, biopsy reports and outcome data were collected. ATIN was calculated by subtracting the percentage of atrophic cortex from the percentage of total cortex with tubulointerstitial inflammation, with ≥10% representing significant ATIN. The primary outcome was a composite of requiring renal replacement therapy or doubling of serum creatinine. RESULTS: In total 153 new cases of IgAN were identified, of which 111 were eligible for inclusion. Of these, 76 (68%) were male and 54 (49%) had ATIN on biopsy. During a median follow-up of 2.3 years, 34 (31%) reached the primary outcome. On univariable Cox regression analysis, ATIN was associated with a five-fold increase in the primary outcome [hazard ratio (HR) (95% confidence interval) 4.9 (95% confidence interval (CI) 2.1-11.3)]. On multivariable analysis, mesangial hypercellularity, tubular atrophy and interstitial fibrosis and ATIN independently associated with renal outcome (P = 0.02 for ATIN). Inter-observer reproducibility revealed fair agreement in the diagnosis of ATIN (κ=0.43, P = 0.05). CONCLUSIONS: Within our centre, ATIN was significantly associated with renal outcome in patients with IgAN, independently of established histological features and baseline clinical characteristics.

The European Renal Association - European Dialysis and Transplant Association (ERA-EDTA) Registry Annual Report 2016: a summary.

BACKGROUND: This article summarizes the ERA-EDTA Registry's 2016 Annual Report, by describing the epidemiology of renal replacement therapy (RRT) for end-stage renal disease (ESRD) in 2016 within 36 countries. METHODS: In 2017 and 2018, the ERA-EDTA Registry received data on patients undergoing RRT for ESRD in 2016 from 52 national or regional renal registries. In all, 32 registries provided individual patient data and 20 provided aggregated data. The incidence and prevalence of RRT and the survival probabilities of these patients were determined. RESULTS: In 2016, the incidence of RRT for ESRD was 121 per million population (pmp), ranging from 29 pmp in Ukraine to 251 pmp in Greece. Almost two-thirds of patients were men, over half were aged ≥65 years and almost a quarter had diabetes mellitus as their primary renal diagnosis. Treatment modality at the start of RRT was haemodialysis for 84% of patients. On 31 December 2016, the prevalence of RRT was 823 pmp, ranging from 188 pmp in Ukraine to 1906 pmp in Portugal. In 2016, the transplant rate was 32 pmp, varying from 3 pmp in Ukraine to 94 pmp in the Spanish region of Catalonia. For patients commencing RRT during 2007-11, the 5-year unadjusted patient survival probability on all RRT modalities combined was 50.5%. For 2016, the incidence and prevalence of RRT were higher among men (187  and 1381 pmp) than women (101 and 827 pmp), and men had a higher rate of kidney transplantation (59 pmp) compared with women (33 pmp). For patients starting dialysis and for patients receiving a kidney transplant during 2007-11, the adjusted patient survival probabilities appeared to be higher for women than for men.

Is it necessary to stop antiplatelet agents before a native renal biopsy?

BACKGROUND: The practice of advising patients to stop antiplatelet agents before an elective renal biopsy is widespread. The aim of this study was to compare the rate of bleeding complications in two centres that have different policies regarding the ongoing use of antiplatelet agents in patients undergoing an elective renal biopsy. Neither centre routinely checks bleeding time before renal biopsy. A secondary aim, therefore, was to compare complication rates from this cohort with those reported in the literature where screening for prolonged bleeding time is standard practice. METHODS: A retrospective study of 1120 biopsies performed by nephrologists under direct ultrasound guidance in the two renal units in Glasgow, Scotland (Jan 2000 to May 2007) was undertaken. Antiplatelet agents were stopped 5 days before biopsy in one centre but continued in the other. Bleeding time was not measured before biopsy and pro-coagulants were not routinely administered. Major bleeding was defined as the need for blood transfusion, surgical or radiological intervention. Minor bleeding was defined as an >or=1.0 g/dL fall in haemoglobin following biopsy without the need for transfusion or intervention. RESULTS: Haemoglobin fell by >or=1.0 g/dL in 221 (19.7%) patients. There were 21 (1.9%) major bleeding complications. No patient died or required nephrectomy. Gender, advancing age or worse renal impairment was not associated with an increased likelihood of bleeding. Bleeding complications in 75 patients continuing antiplatelet agents were compared with those occurring in 60 patients whose antiplatelet agents were discontinued. Minor complications were commoner in the first group (31.0 versus 11.7%; P = 0.008), though there was no difference in the rate of major complications. CONCLUSIONS: The risk of major bleeding following a native renal biopsy under ultrasound guidance is low. Stopping antiplatelet agents before biopsy was associated with a lower rate of minor complications but there was no difference in the rate of major complications. Complication rates compare favourably with other published series in which bleeding time was checked and corrected.

Endothelial function in patients with proteinuric primary glomerulonephritis.

BACKGROUND: Cardiovascular disease is the commonest cause of mortality among patients with end-stage renal disease. Endothelial function and inflammation have previously been shown to be abnormal among such individuals, and are known to be important factors in the progression of atherosclerosis. The aim of this study was to assess endothelial function early in the natural history of renal disease. METHODS: Patients with primary glomerulonephritis, and healthy controls were recruited. In addition to routine laboratory assessment of renal function and proteinuria, assays were undertaken to measure CRP, vWF, VCAM and ICAM. Furthermore, a direct assessment of microvascular endothelial function was undertaken, using laser Doppler imaging to measure perfusion to areas of skin under the influence of transdermally delivered vasodilator agents. RESULTS: Data were collected from 39 patients and 22 controls. No patient was taking anti-platelet agents, statins or angiotensin-converting enzyme inhibitors at the time of endothelial function assessment. All 3 biomarkers of endothelial function were significantly elevated in the patient group compared to controls: ICAM 455 versus 359 ng/ml (p = 0.009), VCAM 1,101 versus 771 ng/ml (p = 0.007) and vWF 184 versus 125 IU/ml (p < 0.001). These differences remained significant after adjusting for blood pressure and body mass index. Endothelium-dependent and endothelium-independent vascular responses were blunted in the patient group, compared to controls (AUC: 2,204 vs. 3,721 PU for dependent and 2,190 vs. 3,555 PU for independent responses). CONCLUSIONS: Microvascular endothelial and vascular smooth muscle function is abnormal in patients with primary glomerulonephritis and moderate proteinuria but well-maintained renal function. We believe these findings to be of particular importance as they compare 2 well-matched groups in the absence of the confounding influence of drugs known to affect endothelial function.