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Introduction We aimed to determine the mortality rate, cause of death, and rate of end-stage kidney disease (ESKD) in adults with nephrotic syndrome (NS). Methods We conducted a national registry–based study, including all 522 adults who had a kidney biopsy for NS in Scotland in 2014–2017. We linked the Scottish Renal Registry to death certificate data. We performed survival and Cox proportional hazards analyses, accounting for competing risks of death and ESKD. We compared mortality rates with those in the age- and sex-matched general population. Results A total of 372 patients had primary NS; 150 had secondary NS. Over a median follow-up of 866 days, 110 patients (21%) died. In patients with primary NS, observed versus population 3-year mortality was 2.1% (95% CI 0.0%–4.6%) versus 0.9% (0.8%–1.0%) in patients aged, Graphical abstract

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.

Recent advances in the world of glomerular diseases have largely focussed on remission induction with immune modulating therapy. It is well recognised that even with the best available treatments, patients with glomerular diseases may have an increased risk of progressive renal and cardiovascular disease.The arrival of large trials looking at the benefits of sodium-glucose cotransporter 2 inhibitors (SGLT2i) in patients with chronic kidney disease (CKD) and diabetes or not has shifted the entire focus of current management and the shift needs to go further. This review summarises the background to these landmark trials and provides practical guidance for implementation of the results in a general nephrology clinic. In sub-group analyses of the Dapagliflozin and Prevention of Adverse Outcomes in Chronic Kidney Disease (DAPA-CKD) clinical trial, SGLT2i improved renal outcomes in patients with immunoglobulin A (IgA) nephropathy highlighting the potential for this drug class in glomerular disease. We also discuss where the gaps in evidence are and where future trials in glomerular diseases, be they primary or secondary, should be focussed.The renal community has never before had evidence of this strength upon which to base recommendations for patients with CKD and we should be grasping it with both hands.

BackgroundSmall 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.MethodsUsing 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.Results339 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).ConclusionsSeasonality 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.

Background:\ud \ud 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).\ud Methods:\ud \ud 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.\ud Results:\ud \ud 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 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.\ud Conclusion:\ud \ud 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.

Background and Aims Outcomes in ANCA vasculitis remain difficult to predict and therapeutic decision-making can be challenging. We aimed to establish if a renal risk score (RRS) could predict outcomes in this population. Method The Scottish Renal Biopsy Registry is a complete national dataset of all renal biopsies performed in Scotland. Those who had a first renal biopsy between 01/01/2014 and 31/12/2017 with evidence of ANCA vasculitis were included. Demographic data, treatment regimens, episodes of relapse and patient and kidney survival were recorded, retrospectively. The RRS was calculated using the system proposed by Brix et al (1). Each patient was categorised according to % of normal glomeruli (N0 >25%, N1 10 to 25%, N2 25%) and eGFR (CKD-EPI) at time of biopsy (eGFR: G0 >15 mL/min/1.73 m2, G1 ≤15 mL/min/1.73 m2). Individual scores were summated and patients defined as low, medium or high risk. Cox proportional hazard models were created for survival to ESKD, relapse and death, stratified by risk category. Analyses were conducted using R statistical software. Results Two-hundred and forty-six patients with biopsy proven ANCA vasculitis were identified. Fifty percent (n=123), 46% (n=112) and 5% (n=11) were stratified as low, medium and high risk respectively. Fifty-two percent (n=129) were male and mean age at biopsy was 66.7±12.2 years. This was similar across the risk categories. Mean eGFR was lower in the high-risk category (High risk 8.6±6.1 ‘v’ Low risk 45.7±26.0 ml/min/1.73m2, p Those categorised as medium or high risk were more likely to receive plasma exchange and/or haemodialysis at presentation (p Conclusion A simple RRS, using routinely reported data, in patients with renal biopsy proven ANCA vasculitis can help to predict development of ESKD. It may also be predictive of future relapse in those with a lower RRS, most likely explained by reduced irreversible damage in this group. The RRS could inform monitoring and treatment decisions. Whilst the numbers are small, a unique strength of this data is that it is based on a complete national dataset making it less susceptible to bias from regional variations in diagnostic and therapeutic practice.

Background and Aims The reported incidence of lupus nephritis (LN) is approximately 6.1 cases per million population per year in Scotland based on Scottish Renal Registry biopsy data. Despite immunosuppressive treatment, approximately 10-30% of patients will progress to established renal failure (ERF) within 15 years. In December 2007, our unit moved from a protocol of Cyclophosphamide/ steroid induction with Azathioprine/ Prednisolone maintenance to Mycophenolate/ steroid induction and maintenance. We undertook this study to compare remission rates before and after this change. Method A retrospective electronic patient record analysis was performed for all patients in our centre with a documented native renal biopsy showing a histopathological diagnosis of LN, between 1 July 1993 and 31 December 2017. Repeat biopsies were excluded. Baseline demographics, histopathological class and first and second line induction and maintenance therapies were recorded. Endpoints analysed were; partial and complete response (as defined in KDIGO Clinical Practice Guideline for Glomerulonephritis 2012), time to achieve this response, relapse, progression to ERF and death. Results 120 patients who underwent a biopsy during the 24.5-year period received a diagnosis of lupus nephritis. 82.5% of patients were Caucasian. Median duration of follow-up was 72 months. 15% of patients died and 5% developed ERF within the follow-up period, representing one death per 56 patient years and one incident case of ERF per 168 patient years. There were 40 patients in the pre-December 2007 group and 80 in the post-December 2007 group. Those in the earlier group were younger, with a mean age of 35.4 years versus 44.8 years in the later group (p=0.002). 23% had class V in the earlier group compared to 15% in the later group (p=0.31). Proportions of female patients were 80% and 75% in the early and late groups respectively (p=0.54). Median creatinine was 106µmol/L in the pre-December 2007 group and 89.5 µmol/L in the post-December 2007 group (p=0.96). Patients in the pre- and post- December 2007 groups had comparable rates of complete response, at 72% and 71% respectively. However, those diagnosed before December 2007 were slower to respond, with a median time to achieve complete response of 10.5 months, compared to 6 months in those diagnosed after 1 December 2007 (p=0.007). Conclusion Following a change in our immunosuppressive induction regimen from Cyclophosphamide/ steroids to Mycophenolate/ steroids, our response rates have remained similar, however speed of attaining remission has improved.

Background and Aims Seasonal variation of ANCA associated vasculitis (AAV) and a possible link to extrinsic infective triggers is predominantly based on single centre epidemiological data. Despite frequent confounding factors including difficulty in identifying the precise time of disease onset, seasonality may be associated with the type of vasculitis and may impact the incidence of renal involvement. Therefore, the aim of this study was to explore if there is an association between seasonality, severity and incidence of biopsy-proven renal vasculitis in the Scottish population. Method Using the Scottish renal biopsy registry, we identified all adult native renal biopsies performed across Scotland between 2014 and 2018 with a diagnosis of AAV, including microscopic polyangiitis (MPA) and granulomatosis with polyangitis (GPA). Demographic data including ANCA antibody status, histological diagnosis, estimated glomerular filtration rate (eGFR) and proteinuria at presentation were recorded. Seasons were defined as autumn (September – November), winter (December-February), spring (March – May) and summer (June - August). Statistical analysis was performed using multivariate ANOVA analysis and Student’s t-test in parametric data. Results 339 cases of biopsy proven AAV were identified and included in the analysis. In this cohort, 53% were female with mean patient age of 65.6 years (± 13). Mean estimated glomerular filtration rate (eGFR) at the time of diagnosis of AAV was 32 (± 27.2) mL/min/1.73m2 and median urinary protein creatinine ratio (uPCR) was 146mg/mmol (IQR 79.8 – 271.3). Diagnosis of MPA n=209(62%) was more common than GPA n=130(38%) and patients with MPA were significantly younger at presentation (63.5 ± 13.6 ‘vs’ 67 ± 12.7 years, p = 0.017). Otherwise, these groups did not differ in mean eGFR (MPA 29.6 ± 25.7 ‘vs’ GPA 34.8 ± 27.6 mL/min/1.73m2) or median uPCR (MPA 147, IQR 78.6 – 286.5 ‘vs’ GPA 139, IQR 80.5 – 261 mg/mmol) at onset. We observed a mean of 3.5 (± 1) new cases of MPA and 2.1 (± 0.7) new cases of GPA per month, with no significant difference observed in month-to-month comparison. Seasonal analysis showed mean occurrence of 11.4 (± 4.5) cases of MPA in autumn, 11.2 (± 4.9) in winter, 10.6 (± 1.5) in spring and 8.6 (± 1.9) in summer months. In GPA, mean 6.6 (±2.7) cases occurred each autumn, 5.4 (± 3) in winter, 7.2 (± 2.9) in spring and 6.4 (± 0.9) in summer months. Overall, no significant differences in monthly or seasonal incidence across 5 years of monitoring were detected. Similarly, we observed no difference in renal function at presentation during different seasons for MPA (mean eGFR range 21.8 – 37.6 mL/min/1.73m2, uPCR median range 112 – 167.5 mg/mmol) or GPA (mean eGFR range 32-37 mL/min/1.73m2; uPCR median range 110 – 244 mg/mmol). Conclusion Our data suggest that there is no seasonal variation in the incidence of AAV diagnosed on kidney biopsy in patients living in Scotland. Additionally, patients present with similar levels of kidney function regardless of season. Thus traditional holiday periods i.e. Easter/Christmas do not seem to lead to a delay in diagnosis. This is the first study to consider seasonality in a complete national cohort and suggests that seasonal extrinsic factors do not play a major role in the pathogenesis leading to AAV onset.

Background and Aims Individuals living in areas of multiple socioeconomic deprivation have reduced life expectancy and experience health inequalities. Chronic kidney disease is more common in areas of social deprivation and these patients are more likely to develop end stage kidney disease. Vasculitis is a rare but significant cause of kidney disease. The impact of socioeconomic status on disease activity or outcomes in patients with ANCA Associated Vasculitis (AAV) is yet to be fully explored. The aim of this study was to establish whether there is an association between the incidence of biopsy-proven renal vasculitis and socioeconomic status, as measured by the Scottish Index of Multiple Deprivation (SIMD). Method Using the Scottish renal biopsy registry, we identified all adult native renal biopsies performed across Scotland between 2014 and 2018 with a diagnosis of AAV. Patient’s postcode and SIMD (2016) rank were recorded. Patients were separated into quintiles of SIMD rank. Baseline demographics were recorded. We derived the denominator population from the 2016 SIMD census. Data were calculated per million population (PMP) served. Results 339 biopsy proven cases of AAV were identified. 6 cases were excluded as postcode was unavailable. Overall, mean age was 65.9 (±13.0) years and 45% of patients were male. At time of diagnosis, mean estimated glomerular filtration rate (eGFR) was 61.7 (±25.7) ml/min/1.73m2 and median urinary protein creatinine ratio (uPCR) was 134mg/mmol (IQR 64-21). Microscopic Polyangiits n=205(65%) was more common than Granulomatosis with Polyangiits n=128(35%). The incidences of kidney biopsy proven AAV were similar across all quintiles of deprivation. In the most deprived 20% of population, incidence rate of kidney biopsy proven AAV was 11.2 per million person-years vs 13.0 per million person-years in least deprived 20% of population. Patients in areas of greatest relative deprivation were younger (64.0 (±12.3) vs. 68.1 (±12.7) years) and had slightly less proteinuria at diagnosis (99mg/mmol (IQR 35-211) vs. 138mg/mmol (IQR 78-281)) when compared to patients living in least deprived areas. However, there was no difference in level of renal function at diagnosis (33.8 (±29.6) ml/min/1.73m2 vs 31.5 (±23.2) ml/min/1.73m2). Conclusion Our complete national dataset shows that there is no significant difference in incidence of renal AAV across the spectrum of socioeconomic deprivation. The analysis of renal function at presentation suggests no evidence of an association between deprivation and delay in diagnosis in a healthcare system free at the point of access.

Background: Hypertension is prevalent in chronic kidney disease (CKD). Studies suggest that reduction in dietary salt intake reduces blood pressure (BP). We studied relationships between salt intake, BP and renin–angiotensin system regulation in order to establish if it is disordered in CKD. Methods: Mechanistic crossover study of CKD patients versus non-CKD controls. Participants underwent modified saline suppression test prior to randomization to either low or high salt diet for 5 days and then crossed over to the alternate diet. Angiotensin-II stimulation testing was performed in both salt states. BP, urea and electrolytes, and plasma aldosterone concentration (PAC) were measured. Results: Twenty-seven subjects were recruited (12 CKD, 15 control). There was no difference in age and baseline BP between the groups. Following administration of intravenous saline, systolic BP increased in CKD but not controls (131 ± 16 to 139 ± 14 mmHg, P=0.016 vs 125 ± 20 to 128 ± 22 mmHg, P=0.38). Median PAC reduced from 184 (124,340) to 95 (80,167) pmol in controls (P=0.003), but failed to suppress in CKD (230 (137,334) to 222 (147,326) pmol (P=0.17)). Following dietary salt modification, there was no change in BP in either group. Median PAC was lower following high salt compared with low salt diet in CKD and controls. There was a comparable increase in systolic BP in response to angiotensin-II in both groups. Discussion: We demonstrate dysregulation of aldosterone in CKD in response to salt loading with intravenous saline, but not to dietary salt modification.

Background: The impact of multiple socio-economic deprivation on patient outcomes in primary renal diseases is unknown. We aimed to assess whether risk of death or requiring renal replacement therapy (RRT) in patients with primary glomerulonephritis (GN) was higher in patients living in an area of multiple socio-economic deprivation. Methods: Patients undergoing native renal biopsy between 2000 and 2014 were identified. Baseline demographics, postcode at time of biopsy, follow-up blood pressure, proteinuria and time to death or RRT were recorded. The Scottish Index of Multiple Deprivation (SIMD) is a multidimensional model used to measure deprivation based on postcode. Using SIMD, patients were separated into tertiles of deprivation. Results: A total of 797 patients were included, 64.2% were male with mean age of 54.1 (standard deviation 17.0) years. Median follow-up was 6.3 (interquartile range 3.7-9.4) years during which 174 patients required RRT and 185 patients died. Patients in the most deprived tertile of deprivation were significantly more likely to die than those in the least deprived tertile [hazard ratio (HR) 2.2, P < 0.001], independent of age, baseline serum creatinine and blood pressure. They were not more likely to require RRT (P = 0.22). The increased mortality risk in the most deprived tertile was not uniform across primary renal diseases, with the association being most marked in focal segmental glomerulosclerosis (HR 7.4) and IgA nephropathy (HR 2.7) and absent in membranous nephropathy. Conclusion: We have demonstrated a significant independent 2-fold increased risk of death in patients with primary GN who live in an area of multiple socio-economic deprivation at the time of diagnosis as compared with those living in less deprived areas.

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.

Background and Aims: Acute tubulointerstitial nephritis (ATIN) is a potentially reversible cause of acute kidney injury with the majority of cases drug related. Our aims were to examine the incidence profile of patients with ATIN in Scotland and to assess the impact of corticosteroid treatment. Design and Methods: All adult patients with biopsy-proven ATIN, diagnosed between 2000 and 2012, presenting to renal units serving 1.9 of Scotland’s 5 million population were included. Patient demographics, presenting, aetiologic and pathologic features, treatment given and outcome were extracted from patient records. Results: In total, 171 cases representing 4.7% of native renal biopsies were identified. Median serum creatinine (sCr) was 327 μmol/l at biopsy (106 μmol/l at baseline). Eosinophilia, fever or rash was present in 57% with all 3 in only 1.1%. Active urinary sediment was found in 68%. Aetiology appeared drug induced in 73%. Proton pump inhibitors (PPIs) were likely causative in almost as many cases as antibiotics (35% each) and were more frequently implicated than non-steroidal anti-inflammatory drugs (20%). Number of PPI-related cases paralleled the rising prescription of these drugs. Corticosteroids were prescribed in 59% of drug-induced ATIN (median sCr at biopsy: 356 μmol/l vs. 280 μmol/l in those managed conservatively). There was no difference in sCr at 1, 6 and 12 months, with similar proportions of both groups experiencing complete renal recovery (48% vs. 41%) and becoming dialysis dependent (10% in both). Conclusions: Incidence of biopsy-proven ATIN in Scotland has been rising over the past decade with the majority of cases drug induced. Evidence supporting corticosteroid treatment is lacking.

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.

Background. Blockade of the mineralocorticoid receptor (MR) in patients with chronic kidney disease (CKD) improves surrogate cardiovascular outcomes, such as left ventricular mass. Animal models of renal disease support a pathological role of mineralocorticoids, in the context of a high sodium intake. We aimed to assess the regulation of mineralocorticoid biosynthesis in patients with CKD. Methods. Seventy patients with CKD stages 3/4 and 30 patients with essential hypertension (EH) were recruited. Patients underwent detailed clinical phenotyping, drug history and biochemical assessment. Patients completed a 24-h urine collection for measurement of urinary tetrahydroaldosterone (THALDO) and tetrahydrocorticosterone (THDOC) excretion rates (measured using gas chromatography-mass spectrometry) and urinary electrolytes. The factors which correlated significantly with THALDO and THDOC excretion were entered into linear regression models. Results. Patients with EH and CKD were well matched with no significant differences in gender, age or weight. The mean estimated glomerular filtration rate (eGFR) in CKD patients was 38.6/min/1.73 m 2 . The mean urinary excretion rates of THALDO, THDOC and 24-h urinary sodium (24-h USod) were not significantly different between CKD and EH patients. The level of renal function did not correlate with THALDO or THDOC excretion. In patients with CKD, 24-h USodium (r= 0.614, P < 0.001) and 24-h UPotassium (r= 0.538, P < 0.001) were positively correlated with THALDO excretion. On multivariate linear regression analysis, 24-h USod was the strongest independent predictor (P = 0.004) of THALDO and THDOC excretion in CKD. In patients with EH, no relationship was seen between mineralocorticoid excretion and 24-h urinary sodium excretion. Conclusions. In patients with CKD, 24-h urinary sodium excretion is the strongest positive predictor of urinary mineralocorticoid excretion. The nature of this relationship is unexpected, novel, not seen in patients with EH and may explain the association seen between high urinary sodium excretion, mineralocorticoids and poor outcomes in patients with CKD.

Background:\ud \ud 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.\ud Methods:\ud \ud 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.\ud Results:\ud \ud 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 30).\ud Conclusions:\ud \ud 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.

Severe acute kidney injury (AKI) among hospitalized patients often necessitates initiation of short-term dialysis. Little is known about the long-term outcome of those who recover to normal renal function. The aim of this study was to determine the long-term renal outcome of patients experiencing AKI requiring dialysis secondary to hypoperfusion injury and/or sepsis who recovered to apparently normal renal function.All adult patients with AKI requiring dialysis in our centre between 1 January 1980 and 31 December 2010 were identified. We included patients who had estimated glomerular filtration rate (eGFR)60 mL/min/1.73 m 2 12 months or later after the episode of AKI. Patients were followed up until 3 March 2015. The primary outcome was time to chronic kidney disease (CKD) (defined as eGFR persistently 60 mL/min/1.73 m 2 ) from first dialysis for AKI.Among 2922 patients with a single episode of dialysis-requiring AKI, 396 patients met the study inclusion criteria. The mean age was 49.8 (standard deviation 16.5) years and median follow-up was 7.9 [interquartile range (IQR) 4.8-12.7] years. Thirty-five (8.8%) of the patients ultimately developed CKD after a median of 5.3 (IQR 2.8-8.0) years from first dialysis for AKI giving an incidence rate of 1 per 100 person-years. Increasing age, diabetes and vascular disease were associated with higher risk of progression to CKD [adjusted hazard ratios (95% confidence interval): 1.06 (1.03, 1.09), 3.05 (1.41, 6.57) and 3.56 (1.80, 7.03), respectively].Recovery from AKI necessitating in-hospital dialysis was associated with a very low risk of progression to CKD. Most of the patients who progressed to CKD had concurrent medical conditions meriting monitoring of renal function. Therefore, it seems unlikely that regular follow-up of renal function is beneficial in patients who recover to eGFR 60 mL/min/1.73 m 2 by 12 months after an episode of AKI.

Background. Premature sudden cardiovascular death is the commonest cause of death in end-stage renal disease (ESRD) patients and is associated with uraemic cardiomyopathy [left ventricular hypertrophy (LVH), systolic dysfunction (LVSD) or LV dilation]. High-energy phosphates (HEP), quantified using phosphorus-31 magnetic resonance spectroscopy, are reduced in patients with diabetes, heart failure and uraemia. Phosphocreatine:b adenosine triphosphate (PCr:ATP) ratio is an index of metabolic activity. We compared resting HEPs in ESRD patients and hypertensive patients (with and without LVH) who had normal renal function (LVH-only or normal myocardia). We also assessed associations of HEP levels with abnormalities of uraemic cardiomyopathy. Methods. Fifty-three ESRD and 30 hypertensive patients (18 with LVH, 12 with normal myocardia) underwent phosphorus magnetic resonance spectroscopy of their left ventricle. PCr:ATP ratios were calculated from 31 P-MR spectra obtained from long-axis views of the left ventricle. Results. There were no significant differences in age, LV mass, chamber sizes and ejection fraction between patient groups. PCr:ATP was significantly lower in ESRD patients compared to hypertensive patients, irrespective of the presence or absence of LVH (P ¼ 0.01). In the ESRD group, PCr:ATP was significantly lower in patients with LVSD (P ¼ 0.05) and LV dilation (P ¼ 0.01). LVH was not associated with significant difference in PCr:ATP. Conclusions. ESRD patients have lower HEP levels compared to hypertensive patients. Lower PCr:ATP ratio, indicating altered myocardial metabolic function in ESRD patients, is associated with features of uraemic cardiomyopathy.

BACKGROUND: Contemporary studies analysing the long-term outcomes of patients with idiopathic membranous nephropathy and nephrotic syndrome in the era of evidence-based antiproteinuric and immunosuppressive therapies are sparse. Controversy also persists regarding which immunosuppression (IS) regimen to use. In this retrospective cohort study, we aimed to characterize time to partial remission (PR), complete remission (CR), requirement for renal replacement therapy (RRT) or death. We aimed to assess which factors predicted RRT or death and determine the impact of IS on outcome. METHODS: Ninety-five consecutive adult patients attending two centres between 1997 and 2008 were identified. Baseline demographics and subsequent treatment and outcome were recorded. RESULTS: Ninety-five percent of patients were prescribed angiotensin-converting enzyme inhibitors and/or angiotensin-receptor blocker (ACEI/ARB) therapy, 78% statin therapy, 70% antiplatelets and 38% IS. The 5-year actuarial rates for PR, CR, RRT and death were 76.4, 24.4, 11.9 and 16.8%, respectively. In patients achieving at least one PR, the 5-year actuarial risk of relapse was 32.8%. Using multivariate survival analysis, achievement of remission was the factor most strongly associated with reduced risk of RRT or death. There was no significant difference in outcomes between patients who did or did not receive IS, although patients receiving IS had more severe disease. Contrary to published findings, 81.8% of patients treated with the Ponticelli regimen (6 months of alternating prednisolone and cyclophosphamide or chlorambucil) suffered significant treatment-related complications compared with 19% of patients prescribed the Cattran regimen (prolonged combined low-dose prednisolone and cyclosporine). CONCLUSIONS: Using an approach of widespread ACEI/ARB treatment and targeted IS, 76% of patients can expect to have achieved at least one PR by 5 years. Achievement of remission is the factor most strongly associated with reduced risk of RRT and death. Treatment with IS is associated with significant treatment complications.

Elevated FGF-23 is a predictor of mortality and is associated with LVH in CKD. It may be a biomarker or a direct toxin. We assessed the relationship between FGF-23 and LVH in CKD using CMRI. In vitro we studied the effect of phosphate, FGF-23, and Klotho on E-selectin and VCAM production in HUVECs. FGF-23 concentration correlates negatively with eGFR and positively with LVMI. FGF-23 was an independent predictor of LVH in CKD. E-selectin and VCAM production was elevated in HUVECs cultured in high phosphate with FGF-23 or Klotho. This effect was attenuated in cells exposed to both FGF-23 and Klotho. FGF-23 is an independent predictor of LVH as measured by CMRI. We show preliminary data which supports that FGF-23 is toxic resulting in activation of the vascular endothelium. We do not prove causality with elevated FGF-23 and LVH. Further research should ascertain if lowering levels of FGF-23 translates to improved clinical outcomes.

Background Left ventricular hypertrophy (LVH) is common in patients with end-stage renal disease (ESRD) and an independent risk factor for premature cardiovascular death. Left atrial volume (LAV), measured using echocardiography, predicts death in patients with ESRD. Cardiovascular magnetic resonance (CMR) imaging is a volume-independent method of accurately assessing cardiac structure and function in patients with ESRD. Study Design Single-center prospective observational study to assess the determinants of all-cause mortality, particularly LAV, in a cohort of ESRD patients with LVH, defined using CMR imaging. Setting & Participants 201 consecutive ESRD patients with LVH (72.1% men; mean age, 51.6 ± 11.7 years) who had undergone pretransplant cardiovascular assessment were identified using CMR imaging between 2002-2008. LVH was defined as left ventricular mass index >84.1 g/m 2 (men) or >74.6 g/m 2 (women) based on published normal left ventricle dimensions for CMR imaging. Maximal LAV was calculated using the biplane area-length method at the end of left ventricle systole and corrected for body surface area. Predictors CMR abnormalities, including LAV. Outcome All-cause mortality. Results 54 patients died (11 after transplant) during a median follow-up of 3.62 years. Median LAV was 30.4 mL/m 2 (interquartile range, 26.2-58.1). Patients were grouped into high (median or higher) or low (less than median) LAV. There were no significant differences in heart rate and mitral valve Doppler early to late atrial peak velocity ratio. Increased LAV was associated with higher mortality. Kaplan-Meier survival analysis showed poorer survival in patients with higher LAV (log rank P = 0.01). High LAV and left ventricular systolic dysfunction conferred similar risk and were independent predictors of death using multivariate analysis. Limitations Only patients undergoing pretransplant cardiac assessment are included. Limited assessment of left ventricular diastolic function. Conclusions Higher LAV and left ventricular systolic dysfunction are independent predictors of death in ESRD patients with LVH.

Renal transplant recipients have a markedly increased risk of premature cardiovascular disease (CVD) compared with the general population, although considerably lower than that of patients receiving maintenance haemodialysis. CVD in transplant recipients is poorly characterised and differs from the nonrenal population, with a much higher proportion of fatal to nonfatal cardiac events. In addition to traditional ischaemic heart disease risk factors such as age, gender, diabetes and smoking, there are additional factors to consider in this population such as the importance of hypertension, left ventricular hypertrophy and uraemic cardiomyopathy. There are factors specific to transplantation such immunosuppressive therapies and graft dysfunction which contribute to this altered risk profile. However, understanding and treatment is limited by the absence of large randomised intervention trials addressing risk factor modification, with the exception of the ALERT study. The approach to managing these patients should begin early and be multifactorial in nature.

Background and objectives: Left ventricular hypertrophy (LVH) is an independent risk factor for premature cardiovascular death in hemodialysis (HD) patients and one of the three forms of uremic cardiomyopathy. Cardiovascular magnetic resonance (CMR) is a volume-independent technique to assess cardiac structure. We used CMR to assess the determinants of left ventricular mass (LVM) and LVH in HD patients. Design, setting, participants, & measurements: A total of 246 HD patients (63.8% male; mean age 51.5 ± 12.1 yr) underwent CMR on a postdialysis day. LVM was measured from a stack of cine loops and indexed for body surface area (LVM index [LVMI]). Demographic, past biochemical, hematologic, and dialysis data were collected by patient record review. Results up to 180 d before CMR were collected. LVH was defined as LVMI >84.1 g/m2 (male) or >76.4 g/m2 (female). Results: A total of 157 (63.8%) patients had LVH. LVH was more common in patients with higher predialysis systolic BP, predialysis pulse pressure, and calcium-phosphate product (Ca × PO4). Furthermore, LVH was significantly associated with higher end-diastolic and systolic volumes and lower ejection fraction. There were positive correlations with LVMI and end-diastolic and systolic volumes. There were weak positive correlations among LVMI, mean volume of ultrafiltration, and Ca × PO4. Using multivariate linear and logistic regression (entering one BP and cardiac variable), the independent predictors of LVMI and LVH were end-diastolic volume, predialysis systolic BP, and Ca × PO4. Conclusions: The principal determinants of LVM and LVH in HD patients are end-diastolic LV volume, predialysis BP, and Ca × PO4.

Premature cardiovascular disease is much more common in renal transplant recipients than the general population, although less common than in patients relying on maintenance haemodialysis. Cardiovascular disease in renal transplant recipients differs from the traditional atherosclerotic model. Although ordinary risk factors such as age, gender, diabetes, hypertension, and smoking still apply, others such as left ventricular hypertrophy and uraemic cardiomyopathy are relevant. Transplantation also adds specific risks such as immunosuppressive therapies and acute rejection. Understanding and managing the cardiovascular risk in this population is limited by a lack of large-scale randomized trials. The approach to managing the cardiovascular risk profile of these patients should be multifactorial and start even before transplantation.

Dietary sodium intake is associated with hypertension and cardiovascular risk in the general population. In patients with chronic kidney disease, sodium intake has been associated with progressive renal disease, but not independently of proteinuria. We studied the relationship between urinary sodium (UNa) excretion and UNa to creatinine ratio and mortality or requirement for renal replacement therapy in chronic kidney disease. Adult patients attending a renal clinic who had ≥1 24-hour UNa measurement were identified. Twenty-four-hour UNa measures were collected and UNa to creatinine ratio calculated. Time to renal replacement therapy or death was recorded. Four hundred twenty-three patients were identified with mean estimated glomerular filtration rate of 48 mL/min per 1.73 m 2 . Ninety patients required renal replacement therapy and 102 patients died. Mean slope decline in estimated glomerular filtration rate was −2.8 mL/min per 1.73 m 2 per year. Median follow-up was 8.5 years. Patients who died or required renal replacement therapy had significantly higher UNa excretion and UNa to creatinine ratio, but the association with these parameters and poor outcome was not independent of renal function, age, and albuminuria. When stratified by albuminuria, UNa to creatinine ratio was a significant cumulative additional risk for mortality, even in patients with low-level albuminuria. There was no association between low UNa and risk, as observed in some studies. This study demonstrates an association between UNa excretion and mortality in chronic kidney disease, with a cumulative relationship between sodium excretion, albuminuria, and reduced survival. These data support reducing dietary sodium intake in chronic kidney disease, but additional study is required to determine the target sodium intake.

Introduction: Excess aldosterone is associated with increased cardiovascular risk. Aldosterone has a permissive effect on vascular fibrosis. Cardiovascular magnetic resonance imaging (CMR) allows study of vascular function by measuring aortic distensibility. We compared aortic distensibility in primary aldosteronism (PA), essential hypertension (EH) and normal controls and explored the relationship between aortic distensibility and pulse wave velocity (PWV).\ud \ud Methods: We studied PA (n=14) and EH (n=33) subjects and age-matched healthy controls (n=17) with CMR, including measurement of aortic distensibility, and measured PWV using applanation tonometry. At recruitment, PA and EH patients had similar blood pressure and left ventricular mass.\ud \ud Results: Subjects with PA had significantly lower aortic distensibilty and higher PWV compared to EH and healthy controls. These changes were independent of other factors associated with reduced aortic distensibility, including aging. There was a significant relationship between increasing aortic stiffness and age in keeping with physical and vascular aging. As expected, aortic distensibility and PWV were closely correlated.\ud \ud Conclusion: These results demonstrate that PA patients display increased arterial stiffness compared to EH, independent of vascular aging. The implication is that aldosterone invokes functional impairment of arterial function. The long-term implications of arterial stiffening in aldosterone excess require further study.

Background Chronic kidney disease (CKD) and coronary artery disease (CAD) are independently associated with increased vascular stiffness. We examined whether renal function contributes to vascular stiffness independently of CAD status. Methods We studied 160 patients with CAD and 169 subjects without CAD. The 4-variable MDRD formula was used to estimate glomerular filtration rate (eGFR); impaired renal function was defined as eGFR Results Patients with CAD and impaired renal function had greater PWV compared to those with CAD and normal renal function (10.2 [9.1;11.2] vs 7.3 [6.9;7.7] m/s; P P P Conclusions Renal function is a determinant of vascular stiffness even in patients with severe atherosclerotic disease. This was paralleled by differences in markers of cell adhesion and inflammation. Increased vascular stiffness may therefore be linked to inflammatory remodeling of the vasculature in people with impaired renal function, irrespective of concomitant atherosclerotic disease.

Background— Primary aldosteronism (PA) is common and associates with excess cardiovascular morbidity independent of blood pressure. Exposure to aldosterone and sodium leads to cardiac fibrosis and hypertrophy in humans and animals possibly mediated by inflammation and oxidative stress. We aimed to clarify the effects of aldosterone excess on myocardial structure and composition in human subjects with PA and essential hypertension using contrast-enhanced cardiac magnetic resonance imaging as well as explore the mechanistic basis for any observed differences. Methods and Results— Twenty-seven subjects with recently diagnosed PA and 54 essential hypertension controls were recruited. Subjects underwent gadolinium-enhanced cardiac magnetic resonance; noninfarct related myocardial fibrosis was identified by a diffuse pattern of late gadolinium enhancement. Patients also underwent assessment of pulse wave velocity, measurement of circulating superoxide anion and C-reactive protein, as well as blood pressure and biochemical assessment. Subjects were well matched with no difference in severity or duration of hypertension. There was a significant increase in the frequency of noninfarct late gadolinium enhancement in PA (70%) when compared with essential hypertension subjects (13%; P Conclusions— These data illustrate that patients with PA exhibit frequent myocardial fibrosis as demonstrated by late gadolinium enhancement using cardiac magnetic resonance imaging; this finding is independent of blood pressure. This may be mediated partly through inflammation and oxidative stress. This study highlights the importance of specific targeting of aldosterone excess as well as blood pressure reduction to minimize cardiac morbidity in PA.

Blockade of the MR (mineralocorticoid receptor) in CKD (chronic kidney disease) reduces LVMI [LV (left ventricular) mass index] and proteinuria. The MR can be activated by aldosterone, cortisol and DOC (deoxycorticosterone). The aim of the present study was to explore the influence of mineralocorticoids on LVMI and proteinuria in patients with CKD. A total of 70 patients with CKD and 30 patients with EH (essential hypertension) were recruited. Patients underwent clinical phenotyping; biochemical assessment and 24 h urinary collection for THAldo (tetrahydroaldosterone), THDOC (tetrahydrodeoxycorticosterone), cortisol metabolites (measured using GC–MS), and urinary electrolytes and protein [QP (proteinuira quantification)]. LVMI was measured using CMRI (cardiac magnetic resonance imaging). Factors that correlated significantly with LVMI and proteinuria were entered into linear regression models. In patients with CKD, significant predictors of LVMI were male gender, SBP (systolic blood pressure), QP, and THAldo and THDOC excretion. Significant independent predictors on multivariate analysis were THDOC excretion, SBP and male gender. In EH, no association was seen between THAldo or THDOC and LVMI; plasma aldosterone concentration was the only significant independent predictor. Significant univariate determinants of proteinuria in patients with CKD were THAldo, THDOC, USod (urinary sodium) and SBP. Only THAldo excretion and SBP were significant multivariate determinants. Using CMRI to determine LVMI we have demonstrated that THDOC is a novel independent predictor of LVMI in patients with CKD, differing from patients with EH. Twenty-four hour THAldo excretion is an independent determinant of proteinuria in patients with CKD. These findings emphasize the importance of MR activation in the pathogenesis of the adverse clinical phenotype in CKD.

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.

Background. Chronic kidney disease (CKD) is associated with increased cardiovascular morbidity and mortality. We hypothesized that the level of proteinuria would correlate with left ventricular mass, providing a potential link between elevated protein excretion, left ventricular hypertrophy (LVH) and the increased mortality seen in patients with CKD. In order to do this, we assessed the determinants of left ventricular mass, measured using cardiac magnetic resonance (CMR) imaging, in patients with CKD. Methods. Patients attending the renal clinic with CKD stages 2-4 and diabetic nephropathy (n = 26) and IgA nephropathy (n = 23) were recruited. They underwent detailed demographic, biochemical and vascular phenotyping and CMR imaging. Proteinuria was measured using spot protein: creatinine ratio (PCR). Left ventricular mass index (LVMI) was calculated from short-axis cine imaging using Argus software and adjusted for body surface area. Results. Log-PCR correlated significantly with LVMI, as did waist circumference, pulse pressure and systolic blood pressure. LVMI was higher in men. When these variables were entered into a linear regression model, log-PCR (P = 0.006) and systolic blood pressure (P < 0.001) independently predicted LVMI. Renal function was not associated with LVMI. Conclusions. Using volume-independent CMR imaging, we have demonstrated that the level of urinary protein excretion is independently and significantly associated with left ventricular mass in patients with CKD. This relationship was independent of blood pressure. This finding provides a novel link between CKD and increased cardiovascular risk.

Renal transplant recipients have a markedly increased risk of premature cardiovascular disease (CVD) compared with the general population, although considerably lower than that of patients receiving maintenance haemodialysis. CVD in transplant recipients is poorly characterised and differs from the nonrenal population, with a much higher proportion of fatal to nonfatal cardiac events. In addition to traditional ischaemic heart disease risk factors such as age, gender, diabetes and smoking, there are additional factors to consider in this population such as the importance of hypertension, left ventricular hypertrophy and uraemic cardiomyopathy. There are factors specific to transplantation such immunosuppressive therapies and graft dysfunction which contribute to this altered risk profile. However, understanding and treatment is limited by the absence of large randomised intervention trials addressing risk factor modification, with the exception of the ALERT study. The approach to managing these patients should begin early and be multifactorial in nature.

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.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.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 (GCFV) (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 GCFV 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 GCFV.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.