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.

Proteoglycan alterations in the rabbit corneal stroma after a lamellar incision.

PURPOSE: To investigate proteoglycans under minimally damaged epithelium after a lamellar microkeratome incision. SETTING: Collaborating university departments. METHODS: Anterior lamellar caps were excised from rabbit corneas and then resutured in place. Healing tissue was examined by electron microscopy with proteoglycan staining. RESULTS: In the weeks after surgery, regions of disorganized stromal matrix were populated by sulfated proteoglycan filaments that were much larger (up to 300 nm long) than those in quiescent stroma. CONCLUSIONS: Large, sulfated proteoglycans existed in rabbit corneas healing from lamellar incisions. These molecules appear to be a normal feature of corneal wound healing; because of their water-binding capacity, they might aid tissue restructuring.

Kikuchi-fujimoto disease: a rare cause of Fever in the returning traveller.

Background. Kikuchi-Fujimoto disease (KFD) is typically a self-limited, benign illness which presents with fever and lymphadenopathy. It is rare in Caucasians, normally occurring in those of Asian descent. The aetiology is poorly understood, but it appears to be an autoimmune disorder with a possible infectious trigger. The clinical features are such that it is often mistaken for infectious diseases or malignancy. Case Report. Here we describe a case of a 36-year-old Asian man who presented following a recent trip to Delhi, India. He described fever, neck swelling, and arthralgia. Given his travel history an infectious cause for his presentation was presumed but multiple investigations were negative. Persistence of his symptoms led to lymph node biopsy to investigate for malignancy; surprisingly this revealed a necrotizing lymphadenitis in keeping with KFD. The patient made a full recovery with supportive treatment only. Conclusion. This case presented an opportunity to reflect on two common presenting complaints-fever in the returning traveller and unexplained lymphadenopathy. Both presentations have a wide range of aetiologies to consider. Although KFD is rare, it is an important diagnosis to make as it can prevent further expensive and invasive investigations, as well as potentially harmful treatments and psychological stress to the patient.

Accurate, reproducible measurement of acetone concentration in breath using selected ion flow tube-mass spectrometry.

Using selected ion flow tube-mass spectrometry (SIFT-MS) for on-line analysis, we aimed to define the optimal single-exhalation breathing manoeuvre from which a measure of expired acetone concentration could be obtained. Using known acetone concentrations in vitro, we determined the instrument's accuracy, inter-measurement variability and dynamic response time. Further, we determined the effects of expiratory flow and volume on acetone concentration in the breath of 12 volunteers and calculated intra-individual coefficients of variation (CVs). At acetone concentrations of 600-3000 ppb on 30 days over 2 months there was an instrument measurement bias of 8% that did not change over time, inter-day and intra-day CVs were 5.6% and 0.0%, respectively, and the 10-90% response time was 500 ± 50 ms (mean ± SE). Acetone concentrations at exhalation flows of 193 ± 18 (mean ± SD) and 313 ± 32 ml s(-1) were 619 ± 1.83 (geometric mean ± logSD) and 618 ± 1.82 ppb in the fraction 70-85% by volume of exhaled vital capacity (V(70-85%)) and 636 ± 1.82 (geometric mean ± logSD) and 631 ± 1.83 ppb in V(85-100%). A difference was observed between acetone concentrations in the V(70-85%) and V(85-100%) fractions (p < 0.01), but flow had no effect. Median intra-individual CVs were 1.6-2.6%. On-line SIFT-MS measurement of acetone concentration in a single exhalation requires control of exhaled volume but not flow, and yields low intra-individual CVs and is potentially useful in approximating blood glucose and monitoring metabolic stress.