Can use of the serum anti-PLA2R antibody negate the need for a renal biopsy in primary membranous nephropathy?

BACKGROUND: Since the emergence of the anti-PLA2R antibody (PLA2R-Ab) test, nephrology practice has not changed dramatically, with most nephrologists still relying on a kidney biopsy to diagnose membranous nephropathy. In this study, we examined the clinical accuracy of the anti-PLA2R antibody test using ELISA in routine clinical care. METHODS: We conducted a retrospective analysis of PLA2R-Ab testing in 187 consecutive patients seen at a single UK centre between 2003 and 2020. We compared the kidney biopsy findings with the PLA2R-ab antibody test. Patients' demography, urine protein creatinine ratios, serum albumin, and treatment characteristics including supportive and immunosuppressive treatment were recorded. The clinical accuracy of the test (e.g. sensitivity and specificity, positive [PPV] and negative [NPV] predictive values) was calculated using the kidney biopsy findings as the diagnostic reference. RESULTS: Mean levels of PLA2R-Ab titre in primary membranous nephropathy were 217RU/ml in comparison to 3RU/ml for both secondary membranous nephropathy and other diagnoses. Most patients with a positive PLA2R-Ab test had a confirmed renal biopsy diagnosis of primary membranous nephropathy with: PPV of 97.3%, sensitivity 75.5%, NPV was 79.8% and specificity was 97.8% at a cut-off threshold of >20 RU/ml. CONCLUSION: The anti-PLA2R antibody test is a highly specific test for diagnosing membranous nephropathy, and the test has the potential to allow for the diagnosis and treatment in up to 75% of PMN cases without the need for a renal biopsy. Nevertheless, patients with negative PLA2R-Ab tests will still require a biopsy to confirm their diagnosis.

The role of noninvasive ventilation in the management of type II respiratory failure in patients with myotonic dystrophy.

Type 1 myotonic dystrophy (DM1) causes sleep disordered breathing and respiratory failure due to a combination of obstructive sleep apnoea, reduced central drive and respiratory muscle weakness. Noninvasive ventilation (NIV) is commonly used for treating respiratory failure in neuromuscular disease; however, there have been few studies assessing the role of NIV in DM1. The aim of this retrospective service evaluation was to investigate the impact of NIV adherence on hypercapnia and symptoms of hypoventilation in patients with DM1. Data on capillary carbon dioxide tension (P CO2 ), lung function, adherence to NIV and symptoms of hypoventilation were obtained from the records of 40 patients with DM1. Mean capillary P CO2 significantly reduced from 6.81±1.17 kPa during supervised inpatient set-up to 5.93±0.82 kPa after NIV set-up (p<0.001). NIV adherence reduced from 7.8 (range: 1.0-11.0) h per 24 h during supervised inpatient set-up to 2.9 (0-10.4) h per 24 h in the community. Overall 72% of patients used NIV <5 h per 24 h during follow-up, including 11% who discontinued NIV completely. There was no correlation between adherence to NIV and changes in capillary P CO2 . Patients who reported symptomatic benefit (50%) had higher adherence than those who did not feel benefit (p<0.05). In conclusion, in patients with myotonic dystrophy with Type II respiratory failure maintaining adherence is challenging.

High level of ß-(1,3)-d-glucan antigenaemia in cystic fibrosis in the absence of invasive fungal disease.

ß-(1,3)-d-glucan (BDG) is used to rule out invasive fungal disease (IFD) but its usefulness in cystic fibrosis (CF) has not been evaluated. We measured serum BDG in CF patients with no clinical suspicion of IFD. Samples from 46 adult CF patients during a stable period and during pulmonary exacerbation were tested. The association of BDG with clinical variables was analyzed. Three hundred and three non-CF patients with suspected IFD were used as comparators. Both samples were negative in 52% of CF patients, whereas 67% of comparators had only negative results (P=0.08). CF patients with pancreatic insufficiency and CF-related diabetes had fewer negative results (P<0.05 for both). Negative results were more common in older CF patients (P<0.05). Use of antibiotics, presence of fungi in sputum and CF liver disease did not impact BDG levels. In conclusion, patients with CF experience significant BDG antigenaemia in the absence of IFD.

A novel antifungal is active against Candida albicans biofilms and inhibits mutagenic acetaldehyde production in vitro.

The ability of C. albicans to form biofilms is a major virulence factor and a challenge for management. This is evident in biofilm-associated chronic oral-oesophageal candidosis, which has been shown to be potentially carcinogenic in vivo. We have previously shown that most Candida spp. can produce significant levels of mutagenic acetaldehyde (ACH). ACH is also an important mediator of candidal biofilm formation. We have also reported that D,L-2-hydroxyisocaproic acid (HICA) significantly inhibits planktonic growth of C. albicans. The aim of the present study was to investigate the effect of HICA on C. albicans biofilm formation and ACH production in vitro. Inhibition of biofilm formation by HICA, analogous control compounds or caspofungin was measured using XTT to measure biofilm metabolic activity and PicoGreen as a marker of biomass. Biofilms were visualised by scanning electron microscopy (SEM). ACH levels were measured by gas chromatography. Transcriptional changes in the genes involved in ACH metabolism were measured using RT-qPCR. The mean metabolic activity and biomass of all pre-grown (4, 24, 48 h) biofilms were significantly reduced after exposure to HICA (p<0.05) with the largest reductions seen at acidic pH. Caspofungin was mainly active against biofilms pre-grown for 4 h at neutral pH. Mutagenic levels (>40 µM) of ACH were detected in 24 and 48 h biofilms at both pHs. Interestingly, no ACH production was detected from D-glucose in the presence of HICA at acidic pH (p<0.05). Expression of genes responsible for ACH catabolism was up-regulated by HICA but down-regulated by caspofungin. SEM showed aberrant hyphae and collapsed hyphal structures during incubation with HICA at acidic pH. We conclude that HICA has potential as an antifungal agent with ability to inhibit C. albicans cell growth and biofilm formation. HICA also significantly reduces the mutagenic potential of C. albicans biofilms, which may be important when treating bacterial-fungal biofilm infections.