Dialysis‐related Amyloidosis: Is It Gone or Should It Be?

The prevalence and severity of dialysis‐related amyloidosis (DRA) appear to have decreased significantly over the last two decades, although recent, large‐scale epidemiological studies show that DRA continues to occur. Recent experimental findings have documented a direct cellular toxicity of β2microglobulin (β2m) fibrils but the mechanisms of β2m fibrillogenesis remain incompletely understood. Although a high plasma concentration of β2m is still considered as a prerequisite for developing DRA, other factors have been clearly incriminated such as older age at dialysis onset and longer dialysis vintage, or suspected effects such as proinflammatory effects of bioincompatible dialysis techniques. Improved dialysis technology has definitely played a role in delaying the onset of the disease, although the respective contributions of high‐flux biocompatible membranes, use of convective mode, and ultrapure dialysate remain imperfectly defined. Importantly, DRA still does exist and no current dialytic modality seems able to fully prevent it. Awaiting further progress in the understanding of DRA pathogenesis, the use of biocompatible high‐flux membranes and ultrapure dialysate is strongly recommended in order to minimize or delay its onset. Convective regimens may provide an additional benefit.     

Post‐transplant erythrocytosis: a disappearing phenomenon?

Abstract: Background: Erythrocytosis is relatively common post‐kidney transplantation and may have adverse consequences. This study examined whether the incidence of erythrocytosis has remained stable over time and explored the impact of this condition on patient outcomes. Methods: This was a retrospective single center review of an incidence cohort (transplanted between 1993 and 2005). Predictors of erythrocytosis and hemoglobin levels and subsequent patient and allograft survival were examined. Results: Erythrocytosis (hemoglobin >170 g/L for >1 month) was observed in 59 of 511 recipients. Erythrocytosis developed in only 8.1% of those transplanted from 1997 to 2005, compared with 18.7% in those transplanted from 1993 to 1996 (p = 0.0005). Independent predictive factors were use of angiotensin converting enzyme inhibitors/angiotensin receptor blockers (ACEi/ARBs) (HR 0.176, 95% CI 0.040–0.71, p = 0.016), male gender (HR 3.72, 95% CI 1.54–9.0, p = 0.003), and mycophenolic acid agents (HR 0.49, 95% CI 0.237–0.99, p = 0.049). Patients with erythrocytosis had superior overall survival (HR for death 0.105, 95% CI 0.014–0.760, p = 0.026) but a trend for worse death censored graft loss (univariate HR 2.06, 95% CI 0.91–4.65, p = 0.084). Conclusions: The incidence of erythrocytosis is falling and is likely related to greater ACEi/ARB use and possibly more antiproliferative immunosuppression. Patient survival is excellent in those with erythrocytosis, but long‐term graft survival may be compromised.     

Should Initial Surveillance of Vestibular Schwannoma Be Abandoned?

Early diagnosis of vestibular schwannoma (VS) has increased in recent years because of increased longevity and availability of magnetic resonance imaging (MRI). Initial conservative radiological surveillance is often requested by patients and physicians to establish whether these tumors are growing before embarking on intervention. Initial observation of at least 1 year in all small VS was therefore recommended by some authors. We evaluated our prospective skull base database of VSs that were managed with initial radiological surveillance to establish when this policy should be abandoned and what predicts future growth. Fifty-four consecutive patients with VS in our institution who were managed by initial yearly MRI scanning were studied. The MRI data were collected prospectively and analyzed by Kodak CareStream viewing software where VS maximum diameters in three perpendicular planes and volume were calculated. One patient was excluded from the analysis as he had only one MRI follow-up. The median age of the 53 patients was 59 years (range, 26 to 86 years), 25 were males and 28 were females, and 33 were under 65 years of age; 18 VSs were extracanalicular, 18 were intracanalicular, and 17 extended both inside and outside the canal; 21 VSs were 1.2 cm³ or less, 22 were 1.2 to 4 cm³, and the rest were >4 cm³. Using volumetric analysis, 29.72% of conservatively managed VS grew by at least 2 mm per year, and 70.82% did not grow in 5 years. Age, gender, symptoms, and side did not predict future growth. However, growth in the first year was a strong predictor of future growth (p < 0.001) and initial volume was also a strong predictor of future growth (p < 0.05). Twenty-nine percent of observed VSs grew by at least 2 mm per year in the first 5 years of surveillance. As the growth rate is slow, initial radiological surveillance is justified in elderly patients and patients with small VSs and nonserviceable hearing. Growth in the first year was a strong predictor of future growth. The reported treatment effect should be interpreted in the light of 70.24% of VSs that either shrink or do not change in the first 5 years.     

Pig‐to‐human heart transplantation: Who goes first?

Cardiac xenotransplantation has recently taken an important step towards clinical reality. In anticipation of the “first‐in‐human” heart xenotransplantation trial, we propose a set of patient characteristics that define potential candidates. Our premise is that, to be ethically justified, the risks posed by current state‐of‐the‐art options must outweigh the anticipated risks of a pioneering xenotransplant procedure. Suitable candidates include patients who are at high immunologic risk because of sensitization to alloantigens, including those who have exhibited early onset or accelerated cardiac allograft vasculopathy. In addition, patients should be considered (1) for whom mechanical circulatory support would be prohibitively risky due to a hypercoagulable state, a contraindication to anticoagulation, or restrictive physiology; (2) with severe biventricular dysfunction predicting unsuccessful univentricular left heart support; and (3) adults with complex congenital heart disease. In conclusion, because the published preclinical benchmark for clinical translation of heart xenotransplantation appears within reach, carefully and deliberately defining appropriate trial participants is timely as the basis for ethical clinical trial design.     

Are lipid‐dependent indicators of cardiovascular risk affected by renal transplantation?

Hyperlipoproteinemia has been reported to frequently occur in kidney transplanted patients, thus possibly explaining, at least in part, the increased incidence of cardiovascular disease in this population. To evaluate the impact of renal transplantation (Tx), and related immunosuppressive therapy, on plasma lipoprotein and Lp(a) profile, we selected a cohort of kidney transplanted patients (36 M/14 F; age 33.8 + 12.0 yr, range 13-62) lacking significant causes of hyperlipidemia. All patients received a triple immunosuppressive regimen and showed a stable renal function after Tx (plasma creatinine: 1.36 +/- 0.35 mg/dL). One year after Tx, we found a significant increase of total cholesterol (TC), LDL, HDL, ApoB and ApoA-I (p < 0.005), while plasma triglyceride levels remained unmodified. Lp(a) plasma levels after Tx were within the normal range and displayed a significant inverse relationship with apo(a) size. Noteworthy, LDL/HDL ratio and ApoB/ ApoA-I ratio in kidney transplanted patients were almost superimposable with those of normal controls. Specifically, LDL/HDL ratio significantly decreased in 64% of patients after Tx, due to a prevalent increase of HDL, and was associated with a moderate amelioration of plasma TG. In a multiple linear regression model, post-Tx HDL level was significantly related to recipient's age, gender, BMI and cyclosporine (CyA) trough levels (Adj-R2 = 0.35, p = 0.0002), with gender and CyA trough levels being the better predictors of HDL. In conclusion, immunosuppressive regimens, in themselves, do not appear to significantly increase the atherogenic risk related to lipoproteins. Rather, other factors can affect the lipoprotein profile and its vascular effects in renal transplant recipients.