Renal biopsy: it is time for pragmatism and consensus.

To obtain truly informed consent, we must be able to advise our patients accurately about the relative risk and benefit of any treatment plan. Percutaneous renal biopsy remains the gold standard investigation in the evaluation of intrinsic renal disease. There have been significant improvements in practice over the past decades with regards to percutaneous renal biopsy. Across centres, we appear now to have reached agreement on many aspects of this procedure, such as the need for blood pressure control, avoidance of coagulopathy, use of spring-loaded needles under direct imaging guidance and a need to monitor for complications. The authors from Rush University Medical Centre provide reassurance that renal biopsy in the modern era remains a safe procedure with a low rate of significant bleeding. There remain areas of divergence in practice that may have unintended and deleterious consequences: administration of desmopressin and discontinuation of aspirin, for example, both carry a risk of thrombosis. It is our opinion that it is time to reach consensus on our interpretation of the available data and to draw up guidelines to standardize our biopsy practice internationally

Venous thromboembolism in primary nephrotic syndrome - is the risk high enough to justify prophylactic anticoagulation?

Background: The reported incidence of venous thromboembolism (VTE) in patients with nephrotic syndrome (NS) varies widely, as does the approach to prophylactic anticoagulation. We aimed to assess the incidence of VTE in patients with primary NS in order to inform a sample size calculation to determine if a future clinical trial will ever be feasible. Methods: All adults undergoing native renal biopsy for NS between 2008 and 2013 yielding a diagnosis of primary glomerulonephritis were identified. Baseline serum albumin, urine protein:creatinine ratio, estimated glomerular filtration rate, date of biopsy and histological diagnosis were recorded. Episodes of objectively verified VTE were identified using the electronic patient record. Sample size calculations were performed based on 2 independent samples with a dichotomous outcome and to achieve a power of 80% and p < 0.05. Results: Two hundred six patients were included of which 60% were male and mean age at biopsy was 55 years (SD 19). Median follow-up was 2.9 years (interquartile range (IQR) 1.6-4.7). Fourteen (6.8%) patients suffered VTE. Median time to diagnosis of VTE from renal biopsy was 36 days (IQR -22 to 178), with 6 VTEs occurring prior to biopsy and 1 during remission. In a total of 270 patient years of NS, there were 7 VTE that could potentially have been avoided if anticoagulation was given for the duration of NS, that is, 2.6% risk per year of NS; this risk was highest for patients with minimal change nephropathy at 13.3% per year of NS, compared to 0.65% per year of NS for those with idiopathic membranous nephropathy. Assuming a 75% reduction in the incidence of VTE with prophylactic anticoagulation, 972 participants would be required for a future clinical trial to have 80% power. Conclusions: Patients with primary NS are at an increased risk of VTE. The timing of VTE means that only half of episodes would be targeted by prophylactic anticoagulation. Given the low frequency of events, a well-powered clinical trial would be challenging to achieve

Risk factors for bleeding complications after nephrologist-performed native renal biopsy

Background: Bleeding is a recognized complication of native percutaneous renal biopsy. This study aimed to describe the incidence of major bleeding after biopsy in a single centre over a 15-year period and examine factors associated with major bleeding. Methods: We identified consecutive adult patients undergoing ultrasound-guided native renal biopsy in the Glasgow Renal and Transplant Unit from 2000 to 2014. From the electronic patient record, we collected data pertaining to biopsy indication, pre- and post-biopsy laboratory measurements, prescribed medication and diagnosis. Aspirin was routinely continued. We defined major bleeding post-biopsy as the need for blood transfusion, surgical or radiological intervention or death. Binary logistic regression analysis was used to assess factors associated with increased risk of major bleeding. Results: There were 2563 patients who underwent native renal biopsy (1499 elective, 1064 emergency). The average age of patients was 57 (SD 17) years and 57.4% were male. Overall, the rate of major bleeding was 2.2%. In all, 46 patients required transfusion (1.8%), 9 patients underwent embolization (0.4%), no patient required nephrectomy and 1 patient died as a result of a significant late retroperitoneal bleed. Major bleeding was more common in those undergoing emergency compared with elective renal biopsy (3.4 versus 1.1%; P < 0.001). Aspirin was being taken at the time of biopsy in 327 of 1509 patients, with no significant increase in the risk of major bleeding (P = 0.93). Body mass index (BMI) data were available for 546 patients, with no increased risk of major bleeding in 207 patients classified as obese (BMI >30). Conclusions: The risk of major bleeding following native renal biopsy in the modern era is low. Complications are more common when biopsy is conducted as an emergency, which has implications for obtaining informed consent. Our data support the strategy of not stopping aspirin before renal biopsy

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

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

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

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

Background: 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: 1) the percentage of non‐fibrotic cortex containing inflammation (NFI‐score), (NFI‐1=0‐24%, NFI‐2=25‐74%, NFI‐3=75‐100%), and 2) 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 eGFR >60 ml/min/1.73m2 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 (OR 16 (95% CI 5.2‐50)). In contrast, TA3 were 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

The interplay between affective and cognitive factors in shaping early proficiency in mathematics

Performing math tasks is a complex process that requires the recruitment of many cognitive and affective factors. Research on the interplay between cognitive and affective factors associated with math ability is surprisingly scarce in primary school children. In the present study, we examined the contribution of both general and mathspecific anxiety to math performance in a large sample of second-grade schoolchildren, and also their relation with different measures of both domain-general (i.e., spatial and verbal working memory, intelligence) and domain-specific cognitive correlates of math ability (i.e., different skills tapping the approximate number system, ANS). Results revealed a negative relation between general anxiety (but not math anxiety) and math performance, beyond the contribution of the cognitive abilities. Importantly, specific components of both verbal working memory (i.e., digit span) and ANS (i.e., approximate addition) mediated the relation between general anxiety and math performance. The educational implications of these findings are discussed

Reactivity to stress and the cognitive components of math disability in grade 1 children

This study investigated the relationship between working memory, processing speed, math performance and reactivity to stress in 83 grade 1 children, 39 with math disability (MD) in comparison to 44 typically achieving (TA) children. The purpose of this study was to investigate the cognitive components of MD and to determine whether stress was interfering with the processes believed to underlie MD. This study is the first to use a physiological index of stress (cortisol levels in saliva) to measure reactivity to stress and learning in children while completing tasks believed to underlie MD. The overall hypothesis was that children with high reactivity would perform more poorly on the working memory tasks believed to underlie MD and that children with MD and high reactivity would exhibit the poorest performance on the tasks that were impaired in children with MD. Nine tasks were administered to assess the core components of MD: working memory for numbers, working memory for words, digits backwards, letter number sequence, digit span forwards, processing speed for numbers and words, block rotation and math tasks. Saliva samples were collected for analysis of cortisol at Time 1 (Ti) as a pre-test baseline and Time 2 (T2) 30-minutes post-test as an index of stress. In addition, on a separate day, samples were collected Time 3 (T3) in the morning and Time 4 (T4) in the afternoon, to establish normal circadian rhythm. Participants were grouped by reactivity levels (high, moderate, and low) for effect size calculation. Children with MD were impaired on the Letter Number Sequence, and Quantitative Concepts tasks. Higher levels of reactivity significantly predicted poorer performance on the Working Memory for Numbers, Working Memory for Words, and Quantitative Concepts tasks. There were no differences between children with MD or TA in cortisol values at any of the times, in reactivity or circadian rhythm. The findings suggest that children with high reactivity may benefit from methods of emotional regulation to reduce reactivity, which may improve learning. Practical implications for educators include attention to the stress response in children, the identification of children with high reactivity and the provision of contextual support.Education, Faculty ofEducational and Counselling Psychology, and Special Education (ECPS), Department ofGraduat