Patient referral is influenced by dialysis centre structure in the Diamant Alpin Dialysis cohort study

BACKGROUND: Late referral (LR) to the nephrologist of patients with progressing chronic kidney disease (CKD) has numerous deleterious effects and is observed in many countries. The contributing factors associated with LR are controversial and poorly defined. We hypothesized that these factors might be better identified by analysing patients starting dialysis in three distinct European countries within the same area. METHOD: The referral and progression of kidney failure patterns were analysed with demographic, clinical and biological data in 279 non-selected consecutive patients starting dialysis in eight centres of three adjacent regions in France, Italy and Switzerland. RESULTS: Early referral (>6 months before the start of dialysis) was seen in 200 patients (71.6%), intermediate referral (1-6 months) in 42 (15.1%) and LR (<1 month) in 37 (13.3%). However inter-centre variations were between 2 and 19% for LR and 6-50% for combined late and intermediate referral. There were no differences at the national levels, but LR was more frequent in the large city centres than in the private or regional structures, with 31 out of 169 (18.3%), two out of 55 (5.4%) and four out of 55 (7.3%), respectively, of their patients (P<0.01). By multivariate analysis, it appears that, besides the presence of an active cancer and the CKD progression rate, the centre structure and the referring physician (primary care physicians and nephrologists are less responsible for LR than other medical specialists) play a significant role in the practice of LR. CONCLUSIONS: Within a dialysis cohort spread over adjacent regions of three countries, LR has the same global distribution pattern, indicating that different health and social security systems do not play a major role in inducing or preventing this practice. The contributing factors for LR that were identified are the type of the referring physician and the structure of the dialysis unit. Both factors are potential targets for an educational and collaborative approach

Neutralization, effector function and immune imprinting of Omicron variants

Currently circulating SARS-CoV-2 variants have acquired convergent mutations at hot spots in the receptor-binding domain$^{1}$ (RBD) of the spike protein. The effects of these mutations on viral infection and transmission and the efficacy of vaccines and therapies remains poorly understood. Here we demonstrate that recently emerged BQ.1.1 and XBB.1.5 variants bind host ACE2 with high affinity and promote membrane fusion more efficiently than earlier Omicron variants. Structures of the BQ.1.1, XBB.1 and BN.1 RBDs bound to the fragment antigen-binding region of the S309 antibody (the parent antibody for sotrovimab) and human ACE2 explain the preservation of antibody binding through conformational selection, altered ACE2 recognition and immune evasion. We show that sotrovimab binds avidly to all Omicron variants, promotes Fc-dependent effector functions and protects mice challenged with BQ.1.1 and hamsters challenged with XBB.1.5. Vaccine-elicited human plasma antibodies cross-react with and trigger effector functions against current Omicron variants, despite a reduced neutralizing activity, suggesting a mechanism of protection against disease, exemplified by S309. Cross-reactive RBD-directed human memory B cells remained dominant even after two exposures to Omicron spikes, underscoring the role of persistent immune imprinting

Chronic kidney disease, severe arterial and arteriolar sclerosis and kidney neoplasia: on the spectrum of kidney involvement in MELAS syndrome

<p>Abstract</p> <p>Background</p> <p>MELAS syndrome (MIM ID#540000), an acronym for Mitochondrial Encephalopathy, Lactic Acidosis and Stroke-like episodes, is a genetically heterogeneous mitochondrial disorder with protean manifestations and occasional kidney involvement. Interest in the latter is rising due to the identification of cases with predominant kidney involvement and to the hypothesis of a link between mitochondrial DNA and kidney neoplasia.</p> <p>Case presentation</p> <p>We report the case of a 41-year-old male with full blown MELAS syndrome, with lactic acidosis and neurological impairment, affected by the "classic" 3243A > G mutation of mitochondrial DNA, with kidney cancer. After unilateral nephrectomy, he rapidly developed severe kidney functional impairment, with nephrotic proteinuria. Analysis of the kidney tissue at a distance from the two tumor lesions, sampled at the time of nephrectomy was performed in the context of normal blood pressure, recent onset of diabetes and before the appearance of proteinuria. The morphological examination revealed a widespread interstitial fibrosis with dense inflammatory infiltrate and tubular atrophy, mostly with thyroidization pattern. Vascular lesions were prominent: large vessels displayed marked intimal fibrosis and arterioles had hyaline deposits typical of hyaline arteriolosclerosis. These severe vascular lesions explained the different glomerular alterations including ischemic and obsolescent glomeruli, as is commonly observed in the so-called "benign" arteriolonephrosclerosis. Some rare glomeruli showed focal segmental glomerulosclerosis; as the patient subsequently developed nephrotic syndrome, these lesions suggest that silent ischemic changes may result in the development of focal segmental glomerulosclerosis secondary to nephron loss.</p> <p>Conclusions</p> <p>Nephron loss may trigger glomerular sclerosis, at least in some cases of MELAS-related nephropathy. Thus the incidence of kidney disease in the "survivors" of MELAS syndrome may increase as the support therapy of these patients improves.</p

Imprinted antibody responses against SARS-CoV-2 Omicron sublineages

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Omicron sublineages carry distinct spike mutations resulting in escape from antibodies induced by previous infection or vaccination. We show that hybrid immunity or vaccine boosters elicit plasma-neutralizing antibodies against Omicron BA.1, BA.2, BA.2.12.1, and BA.4/5, and that breakthrough infections, but not vaccination alone, induce neutralizing antibodies in the nasal mucosa. Consistent with immunological imprinting, most antibodies derived from memory B cells or plasma cells of Omicron breakthrough cases cross-react with the Wuhan-Hu-1, BA.1, BA.2, and BA.4/5 receptor-binding domains, whereas Omicron primary infections elicit B cells of narrow specificity up to 6 months after infection. Although most clinical antibodies have reduced neutralization of Omicron, we identified an ultrapotent pan-variant–neutralizing antibody that is a strong candidate for clinical development

Associations between depressive symptoms and disease progression in older patients with chronic kidney disease: results of the EQUAL study

Background Depressive symptoms are associated with adverse clinical outcomes in patients with end-stage kidney disease; however, few small studies have examined this association in patients with earlier phases of chronic kidney disease (CKD). We studied associations between baseline depressive symptoms and clinical outcomes in older patients with advanced CKD and examined whether these associations differed depending on sex. Methods CKD patients (&gt;= 65 years; estimated glomerular filtration rate &lt;= 20 mL/min/1.73 m(2)) were included from a European multicentre prospective cohort between 2012 and 2019. Depressive symptoms were measured by the five-item Mental Health Inventory (cut-off &lt;= 70; 0-100 scale). Cox proportional hazard analysis was used to study associations between depressive symptoms and time to dialysis initiation, all-cause mortality and these outcomes combined. A joint model was used to study the association between depressive symptoms and kidney function over time. Analyses were adjusted for potential baseline confounders. Results Overall kidney function decline in 1326 patients was -0.12 mL/min/1.73 m(2)/month. A total of 515 patients showed depressive symptoms. No significant association was found between depressive symptoms and kidney function over time (P = 0.08). Unlike women, men with depressive symptoms had an increased mortality rate compared with those without symptoms [adjusted hazard ratio 1.41 (95% confidence interval 1.03-1.93)]. Depressive symptoms were not significantly associated with a higher hazard of dialysis initiation, or with the combined outcome (i.e. dialysis initiation and all-cause mortality). Conclusions There was no significant association between depressive symptoms at baseline and decline in kidney function over time in older patients with advanced CKD. Depressive symptoms at baseline were associated with a higher mortality rate in men

Renal transplantation from cadaveric donor after myocardial revascularization: still a matter of concern?

Renal transplantation in patients who have undergone coronary revascularization remains a matter of concern, few experiences have been reported in literature. From January 1997 to March 2003, 23 previously revascularized patients underwent renal transplants from cadaveric donors. We analyzed patient survival and cardiac events in this group of patients (group A) versus a similar population of 38 revascularized patients who were still on dialysis (group B) on the active waiting list (awl). After a similar follow-up (29.30 +/- 21.34 months versus 32.98 +/- 31.33 months; P = .56), survival was 100% for renal transplant patients and 94.74% for dialysis patients, two of whom (5.26%) died from acute myocardial infarction and four (10.52%) were excluded from the waiting list because of cardiac problems. The event-person ratio was 0.51 for group A patients (75% of events clustered within the first 6 months) and 0.71 for group B. The need for therapy with nitrates decreased from 11/23 (47.8%) to 6/23 (26%) after transplant. The ejection fraction remained stable (53.82% +/- 10.4% vs pre-Tx value of 54.8% +/- 9.4%). Renal survival was 100% (sCr = 1.4 +/- 0.4 mg/dL). Although no statistical significance has emerged, there was a general trend in favor of transplanted patients. On the basis of this experience we believe that coronary revascularization per se should no longer be a matter of concern for renal transplantation, which could be superior to dialysis for this type of patient