Human papillomavirus is detected in transitional cell carcinoma arising in renal transplant recipients

"This is a non-final version of an article published in final form in Pathology The Journal of the Royal College of Pathologists of Australasia 41 (3) pp.245-247"Aims: We investigated the role of human papillomavirus HPV in the development of transitional cell carcinoma TCC arising in renal transplant recipients. Methods: Genomic DNA was extracted from 10 m paraffin embedded sections of five TCCs arising in five renal transplant recipients using the QIAamp DNA mini kit according to the manufacturer's instructions. β-globin PCR was performed to test DNA adequacy. Samples were tested for the presence of HPV DNA by broad spectrum HPV PCR method using non-biotinylated SPF10 primers SPF1A, SPF1B, SPF1C, SPF1D, SPF2B, SPF2D which amplify a short 65 bp fragment. Positive bands were identified on a 3 gel. Positive samples underwent a second HPV PCR and were amplified using biotinylated SPF10 primer set, which amplifies the same 65 bp region of the L1 open reading frame. INNO-LiPA line probe assay was then performed to genotype the samples which uses a reverse hybridisation principle. Results: Four of five TCCs examined were positive for HPV. The high risk HPV16 was detected in three cases whereas in the fourth case an unclassifiable HPV genotype was present. In all DNA samples, β-globin amplification was successful. Conclusions: Our results indicate that HPV and in particular HPV16 may play an aetiological role in the development of TCC in renal transplant patients.Peer reviewedSubmitted Versio

The myogenic response in uremic hypertension

The myogenic response in uremic hypertension.BackgroundThe constriction of resistance arteries in response to an increase in transmural pressure, the myogenic response, is thought to be an important determinant of peripheral vascular resistance and therefore of arterial blood pressure. Since raised peripheral resistance is known to occur in uremic hypertension, abnormal myogenic constriction might be responsible. We sought to assess the myogenic response of resistance arteries from the subtotal nephrectomy rat model of uremic hypertension.MethodsUremic Wistar-Kyoto (WKYU) rats, and sham-operated normotensive (WKYC) and spontaneously hypertensive (SHRC) controls were studied in parallel. Skeletal muscle arteries were mounted on a pressure myograph and allowed to develop myogenic constriction. The active internal diameter was measured at increasing lumen pressures from 20 to 200 mm Hg. Vascular smooth muscle then was relaxed in a calcium free solution containing nitroprusside, and the passive internal diameter measured at the same pressure steps. The ratio of active to passive diameter at any given pressure was used to assess the myogenic response.ResultsMyogenic constriction was not increased in either WKYU or SHRC compared to WKYC at pressures up to 180 mm Hg.ConclusionsIncreased myogenic tone is not the cause of uremic hypertension

Do oral aluminium phosphate binders cause accumulation of aluminium to toxic levels?

<p>Abstract</p> <p>Background</p> <p>Aluminium (Al) toxicity was frequent in the 1980s in patients ingesting Al containing phosphate binders (Alucaps) whilst having HD using water potentially contaminated with Al. The aim of this study was to determine the risk of Al toxicity in HD patients receiving Alucaps but never exposed to contaminated dialysate water.</p> <p>Methods</p> <p>HD patients only treated with Reverse Osmosis(RO) treated dialysis water with either current or past exposure to Alucaps were given standardised DFO tests. Post-DFO serum Al level > 3.0 μmol/L was defined to indicate toxic loads based on previous bone biopsy studies.</p> <p>Results</p> <p>39 patients (34 anuric) were studied. Mean dose of Alucap was 3.5 capsules/d over 23.0 months. Pre-DFO Al levels were > 1.0 μmol/L in only 2 patients and none were > 3.0 μmol/L. No patients had a post DFO Al levels > 3.0 μmol/L. There were no correlations between the serum Al concentrations (pre-, post- or the incremental rise after DFO administration) and the total amount of Al ingested.</p> <p>No patients had unexplained EPO resistance or biochemical evidence of adynamic bone.</p> <p>Conclusions</p> <p>Although this is a small study, oral aluminium exposure was considerable. Yet no patients undergoing HD with RO treated water had evidence of Al toxicity despite doses equivalent to 3.5 capsules of Alucap for 2 years. The relationship between the DFO-Al results and the total amount of Al ingested was weak (R²= 0.07) and not statistically significant. In an era of financial prudence, and in view of the recognised risk of excess calcium loading in dialysis patients, perhaps we should re-evaluate the risk of using Al-based phosphate binders in HD patients who remain uric.</p

Evidence of a causal and modifiable relationship between kidney function and circulating trimethylamine N-oxide

The host-microbiota co-metabolite trimethylamine N-oxide (TMAO) is linked to increased cardiovascular risk but how its circulating levels are regulated remains unclear. We applied "explainable" machine learning, univariate, multivariate and mediation analyses of fasting plasma TMAO concentration and a multitude of phenotypes in 1,741 adult Europeans of the MetaCardis study. Here we show that next to age, kidney function is the primary variable predicting circulating TMAO, with microbiota composition and diet playing minor, albeit significant, roles. Mediation analysis suggests a causal relationship between TMAO and kidney function that we corroborate in preclinical models where TMAO exposure increases kidney scarring. Consistent with our findings, patients receiving glucose-lowering drugs with reno-protective properties have significantly lower circulating TMAO when compared to propensity-score matched control individuals. Our analyses uncover a bidirectional relationship between kidney function and TMAO that can potentially be modified by reno-protective anti-diabetic drugs and suggest a clinically actionable intervention for decreasing TMAO-associated excess cardiovascular risk