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Background: High intrapatient tacrolimus variability has been associated with worse clinical outcomes postrenal transplantation. Theoretically, tacrolimus levels consistently outside the target therapeutic window may result in allograft dysfunction as subtherapeutic tacrolimus levels predispose to episodes of acute rejection, whereas supratherapeutic levels may cause nephrotoxicity., Methods: We investigated the effect of tacrolimus variability in a "Symphony" style low-dose tacrolimus based regime, by collecting data from 432 patients over a 4-year period.Three hundred seventy-six patients were included, with a mean follow-up of 1495 days. Tacrolimus variability 6 to 12 months after renal transplantation was calculated, and outcomes were compared in low (n = 186) and high variability (n = 190) groups., Results: High variability patients were found to be at increased risk of rejection during the first posttransplant year (P = 0.0054) and to have reduced rejection-free survival (hazard ratio, 1.953; 95% confidence interval, 1.234-3.093; P = 0.0054). High variability patients had significantly worse (P < 0.0001) glomerular filtration rates at 1, 2, 3, and 4 years posttransplant. High variability patients were at increased risk of allograft loss (hazard ratio, 4.928; 95% confidence interval, 2.050-11.85; P = 0.0004)., Conclusions: This suggests that highly variable tacrolimus levels predict worse outcomes postrenal transplantation, although the causal nature of this relationship remains unclear. High tacrolimus variability may identify a subset of patients who warrant increased surveillance and patient education regarding dietary and medication compliance.

Female renal transplant recipients of childbearing age may ask what the outcomes are for pregnancy and whether pregnancy will affect graft function. We analyzed obstetric and transplant outcomes among renal transplant recipients in our center who have been pregnant between 1973 and 2013. A case-cohort study was performed identifying 83 pairs of pregnant and non-pregnant controls matched for sex, age, transplant vintage, and creatinine. There were 138 pregnancies reported from 89 renal transplant recipients. There were live births in 74% of pregnancies with high prevalence of prematurity (61%), low birth weight (52%), and pre-eclampsia (14%). Lower eGFR (OR 0.98; p = 0.05) and higher uPCR (OR 1.86; p = 0.02) at conception were independent predictors for poor composite obstetric outcome. Lower eGFR (OR 0.98; p = 0.04), higher uPCR (OR 1.50; p = 0.04), and live organ donation (OR 0.35; p = 0.02) were predictors of ≥20% loss of eGFR between immediately pre-pregnancy and one yr after delivery. There was no difference in eGFR at one, five, and 10 yr in pregnant women compared with non-pregnant controls and a pregnancy was not associated with poorer 10-yr transplant or 20-yr patient survival. Despite high rates of obstetric complications, most women had successful pregnancies with good long-term transplant function., (© 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

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

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.

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

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

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

Highlights from the article: Method to score percentage of non-atrophic renal cortex containing active tubulointerstitial inflammation (ATIN) in All adult patients with a native renal biopsy diagnosis of IgAN between 2010 and 2015 in a unit serving 1.5 million people Within our centre, ATIN was significantly associated with renal outcome in patients with IgAN, independently Patients received immunosuppression had ATIN on biopsy, of.