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.

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.

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.

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.

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.

Multiple socioeconomic deprivation and impact on survival in patients with primary glomerulonephritis.

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.

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.

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.

Predictors of sustained arteriovenous access use for haemodialysis.

BACKGROUND: Guidelines encourage early arteriovenous (AV) fistula (AVF) planning for haemodialysis (HD). The aim of this study was to estimate the likelihood of sustained AV access use taking into account age, sex, comorbidity, anatomical site of first AVF and, for pre-dialysis patients, eGFR and proteinuria. METHODS: 1,092 patients attending our centre who had AVF as their first AV access procedure between January 1, 2000 and August 23, 2012 were identified from the electronic patient record. The primary end-point was time to first sustained AV access use, defined as use of any AV access for a minimum of 30 consecutive HD sessions. RESULTS: 52.9% (n = 578) of the patients ultimately achieved sustained AV access use. The main reasons for AV access non-use were AVF failure to mature and death. The 3-year Kaplan-Meier probability of sustained AV access use was 68.8% for those not on renal replacement therapy (RRT) (n = 688) and 74.2% for those already on RRT (n = 404) at the time of first AVF. By multivariate analysis in patients not on RRT, male sex (HR 2.22; p < 0.001), uPCR (HR 1.03; p = 0.03) and eGFR (hazard ratio, HR 0.85; p < 0.001) were independent predictors of AV access use. In patients already on RRT, age (HR 0.98; p < 0.001) and peripheral vascular disease (HR 0.48; p = 0.02) were independent predictors of AV access use. CONCLUSION: Our data suggest that refinement of the current guideline for timing of AV access creation in planning RRT is justified to take into account individual factors that contribute to the likelihood of technical success and clinical need.

Association between urinary sodium, creatinine, albumin, and long-term survival in chronic kidney disease.

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.

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.

Proteinuria and outcome after renal transplantation: ratios or fractions?

BACKGROUND: Proteinuria is associated with poorer outcomes in renal transplant recipients. Fractional excretion of total protein (FEPR) may better reflect kidney damage than urine protein-to-creatinine ratio (PCR). METHODS: We assessed FEPR (FEPR = [serum creatinine × urine protein] / [serum protein × urine creatinine], %) and PCR ([urinary protein/urinary creatinine] × 1000, mg/mM) 1 year after first renal transplantation as predictors of transplant failure. The primary endpoints were transplant failure and death. The use of the tests was analyzed by constructing receiver operator characteristic curves and comparing the area under the curve. Using receiver operator characteristic analysis, patients were stratified into high- and low-risk groups. RESULTS: Two hundred nineteen recipients were followed up for a median of 4.9 years. At a median of 2.7 years, 11.4% (n=25) of the transplants failed. Eight percent (n=17) of the patients died. The area under the curve was higher for FEPR than PCR (0.92 vs. 0.84). Patients with an FEPR of 0.019% or higher had a 3.4-fold (P=0.003) increased risk of transplant failure and a 2.3-fold (P=0.02) increased risk of death compared with those with an FEPR of less than 0.019%. Patients with a PCR of 97 mg/mM or greater had a 2.1-fold (P=0.04) increased risk of transplant failure and a 1.6-fold (P=0.04) increased risk of death compared with those with a PCR of less than 97 mg/mM (P=0.04). In multivariate analysis with time to transplant failure as the dependent variable, FEPR and PCR were independent predictors of transplant failure (hazards ratio, 1.07 [P=0.013] and 1.03 [P=0.03], respectively). CONCLUSIONS: FEPR and PCR at 1 year are independent predictors of transplant failure, but FEPR may be superior.

Deceased donor transplantation in the elderly--are we creating false hope?

BACKGROUND: Increasing numbers of older patients are developing established renal failure and considering kidney transplant as a renal replacement therapy (RRT) option. The probability of older patients actually receiving a deceased donor kidney transplant is unclear, preventing informed choice about pursuing the option of transplantation. We sought to analyse our RRT population to determine the probability of receiving a deceased donor kidney transplant in patients commencing RRT categorized by age and for whom there was no suitable living kidney donor. METHODS: Patients commencing dialysis in our centre between 1992 and 2009 were identified. Time to listing on the deceased donor transplant waiting list and time to first deceased donor transplant were determined by Kaplan-Meier analysis for patients, categorized by age, with censoring at the date of first living donor kidney transplant, death or last dialysis. RESULTS: One-thousand-five-hundred-and-thirteen patients were categorized into groups by age in years [1: <35 (n = 134), 2: 35-49.9 (n = 207), 3: 50-64.9 (n = 415), 4: >65-74.9 (n = 438) and 5: ≥ 75 (n = 319)]. The probability of being listed for deceased donor transplant within 1 year of commencing RRT was 75, 54, 27, 4 and 0.8% in Groups 1-5, respectively. If listed, the probability of receiving a deceased donor transplant within 5 years of starting RRT was 81, 48, 26, 8 and 0% in Groups 1-5, respectively. In Groups 1-4, 93% (n = 63), 87% (n = 65), 76% (n = 45) and 100% (n = 7) of the patients, respectively, who received a deceased donor transplant were alive and off dialysis 1 year after transplant. The reason patients who were listed did not receive a transplant was usually death on the waiting list. CONCLUSIONS: The likelihood of being listed for transplant falls with increasing age at the time of starting RRT. Even for patients listed for transplant, the probability of older patients actually receiving a transplant is much lower than for younger patients, with only 8% of listed patients aged 65-74.9 years being transplanted within 5 years. This is partly the result of death on the waiting list but may also be related to organ allocation policies. Assessment for possible deceased donor transplantation involves a considerable investment in time and effort for the patient, as well as in health care resources, and a patient's decision whether to proceed with assessment should be informed by the kind of information we have produced. As there may be regional and national variations in practice, each centre should generate such data for use locally.

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.

Validation of the Toronto formula to predict progression in IgA nephropathy.

BACKGROUND/AIM: Predicting outcome in IgA nephropathy (IgAN) is difficult. The Toronto formula uses average mean arterial blood pressure and proteinuria during the first 2 years of follow-up (MAP(0-2), UP(0-2)) to predict the subsequent slope of estimated creatinine clearance (eCrCl). We aimed to validate the Toronto formula in a Scottish cohort and test the hypothesis that adding the slope eCrCl over the first 2 years of follow-up (eCrCl(0-2)) would improve the predictive utility of a similar multivariate model. METHODS: Adultsfrom our centre with biopsy-proven IgAN (n = 169) and at least 2 years of follow-up (median 129.4 months) were included. Clinical data were used to calculate MAP(0-2),UP(0-2),slope eCrCl(0-2 )and predicted slope eCrCl (using the Toronto formula). RESULTS: There was a significant correlation between predicted slope eCrCl using the Toronto formula and actual slope eCrCl (R(2 =) 0.21; p < 0.001). The formula predicted the actual rate of progression to within 4 ml/min/year in 75% of subjects, predicting patients with the most rapid deterioration with the greatest accuracy. The multivariate linear regression model created in our cohort using the same independent variables as the Toronto formula to predict the overall slope eCrCl had an R(2) of 0.22 (p < 0.001) and adding the slope CrCl(0-2) only increased this to 0.25. CONCLUSIONS: The Toronto formula is valid in a European population and useful for identifying patients at high risk of future deterioration in renal function. Adding slope eCrCl(0-2) to a predictive model containing MAP(0-2), andUP(0-2 )does not appear to improve prediction of the overall slope of eCrCl.

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.