No abstract

These findings suggest that too small graft size, frequent in female-to-male transplants, could cause hypertrophy in both kidneys and glomeruli, thereby affecting allograft function and survival.

Lysosomal associated membrane protein 2 (LAMP2) is physiologically implicated in autophagy. A genetic LAMP2 defect causes Danon disease, which consists of two major phenotypes of myopathy and cardiomyopathy. In addition, arteriopathy may manifest on rare occasions but the pathological basis remains unknown. We encountered two Danon families that developed small-vessel vasculopathy in the coronary or cerebral arteries. To investigate the underlying mechanisms, we characterized the biological features of LAMP-2–deficient mice and cultured cells. LAMP-2–deficient mice at 9–24 months of age showed medial thickening with luminal stenosis due to proliferation of vascular smooth muscle cells (VSMC) in muscular arteries. Ultrastructural analysis of VSMC revealed various autophagic vacuoles scattered throughout the cytoplasm, suggesting impaired autophagy of long-lived metabolites and degraded organelles (i.e., mitochondria). The VSMC in Lamp2 null mice expressed more vimentin but less α-smooth muscle actin (α-SMA), indicating a switch from contractile to synthetic phenotype. Silencing of LAMP2 in cultured human brain VSMC showed the same phenotypic transition with mitochondrial fragmentation, enhanced mitochondrial respiration, and overproduction of reactive oxygen species (ROS). These findings indicate that LAMP-2 deficiency leads to arterial medial hypertrophy with the phenotypic conversion of VSMC, resulting from age-dependent accumulation of cellular waste generated by aberrant autophagy.

Decreased excretion of urinary A-megalin in four out of five patients with OCRL mutations suggests that LMW proteinuria may be caused by impaired megalin recycling within the proximal tubular cells. Homologous enzymes, similar to inositol polyphosphate-5-phosphatase B in mice, may help to compensate for defective OCRL-1 function during early childhood.

BackgroundCongenital nephrotic syndrome (CNS) is a rare disorder caused by various structural and developmental defects of glomeruli. It occurs typically as an isolated kidney disorder but associates sometimes with other systemic, extrarenal manifestations.Case PresentationsAn infant presented with severe CNS, which progressed rapidly to renal failure at age of 3 months and death at 27 months. The clinical phenotypes and genetic causes were studied, including the renal pathology at autopsy.Besides the CNS, the affected child had remarkable right-side predominant eye-ball hypoplasia with bilateral anterior chamber dysgenesis (microcoria). Brain MRI revealed grossly normal development in the cerebrum, cerebellum, and brain stem. Auditory brainstem responses were bilaterally blunted, suggesting a defective auditory system. At autopsy, both kidneys were mildly atrophied with persistent fetal lobulation. Microscopic examination showed a diffuse global sclerosis. However, despite of the smaller size of glomeruli, the nephron number remained similar to that of the age-matched control. Whole-exome sequencing revealed that the affected child was compound heterozygous for novel truncating LAMB2 mutations: a 4-bp insertion (p.Gly1693Alafs*8) and a splicing donor-site substitution (c.1225 + 1G > A), presumably deleting the coiled-coil domains that form the laminin 5–2-1 heterotrimer complex.ConclusionsOur case represents a variation of Pierson syndrome that accompanies CNS with unilateral ocular hypoplasia. The average number but smaller glomeruli could reflect either mal-development or glomerulosclerosis. Heterogeneous clinical expression of LAMB2 defects may associate with the difference in fetal β1 subtype compensation among affected tissues. Further study is necessary to evaluate incidence and features of auditory defect under LAMB2 deficiency.Electronic supplementary materialThe online version of this article (doi:10.1186/s12882-017-0632-4) contains supplementary material, which is available to authorized users.

Background Cardiac amyloidosis, a progressive cardiac disease, results from the accumulation of undegraded proteinaceous substrates in the extracellular matrix of the heart. It may present as acute coronary syndrome (ACS); therefore, a clear distinction remains challenging in clinical practice. We describe a case of cardiac amyloidosis mimicking ACS. Case summary A 72-year-old man experienced chest discomfort for 2 days. He gradually developed dyspnoea during the preceding month. Electrocardiogram (ECG) showed sinus rhythm with right bundle branch block and low voltage. Echocardiography revealed concentric left ventricular thickening, biatrial dilation, and preserved ejection fraction with predominantly left ventricular basal hypokinesis. Serial testing of the cardiac biomarkers showed persistently increased high-sensitive cardiac troponin T levels and normal serum creatine kinase myocardial band levels. He was diagnosed with ACS with haemodynamic stability. However, coronary angiography demonstrated non-obstructive coronary arteries. Furthermore, significant macroglossia and periorbital purpura were noticed. Laboratory investigations revealed elevated serum immunoglobulin free light chain (FLC) kappa and lambda levels with an increased FLC ratio. Histological analysis of the biopsied abdominal skin confirmed amyloidosis. Discussion Cardiac amyloidosis often presents as restrictive cardiomyopathy. The usual symptoms include dyspnoea and peripheral oedema. Chest pain may manifest rarely, leading to misdiagnosis as coronary artery disease. Some findings suggestive of cardiac amyloidosis include clinical signs such as amyloid deposits, dyspnoea, low ECG voltage, and basal-predominant hypokinesis with relative apical sparing in echocardiography. Serum FLC test and abdominal skin biopsy can confirm the diagnosis of amyloidosis when a myocardial biopsy is not feasible.

Purpose We aimed to investigate the prevalence and factors associated with falls in older adult outpatients during the coronavirus disease (COVID-19) pandemic in Vietnam. Patients and Methods From February 2022 to June 2022, this cross-sectional study included 814 patients (aged ≥60 years; mean age 71.8 ± 7.3 years; women, 65.2%) attending three geriatric clinics for a comprehensive geriatric assessment. Self-reported fall events in the past 12 months and post-COVID-19 falls were assessed. Factors associated with falls were determined using logistic regression analysis. Results In total, 188 patients (23.1%) had falls (single fall, 75.5%; recurrent falls, 24.5%). The most frequent location, time, and circumstance of falls were the bedroom (43.1%), morning (54.3%), and dizziness (34.6%), respectively. Most patients experienced health issues after falls (bruise/grazes, 53.7%; fracture, 12.8%; immobility, 9.6%; hospital admission, 14.9%). In the adjusted model, factors associated with falls were being underweight (odds ratio [OR] 2.50, 95% confidence interval [CI] 1.37–4.56, P = 0.003), limitations in instrumental activities of daily living (OR 2.03, 95% CI 1.05–3.95, P = 0.036), poor sleep quality (OR 1.83, 95% CI 1.10–3.05, P = 0.020), and fear of falling (OR 3.45, 95% CI 2.23–5.33, P <0.001). Among 357 COVID-19 infected patients, post-COVID-19 falls occurred in 35 patients (9.8%) and were associated with fear of falling (OR 3.14, 95% CI 1.18–8.40, P = 0.023) and post-COVID-19 lower limb weakness (OR 2.55, 95% CI 1.07–6.10, P = 0.035). Conclusion Our study found a substantial prevalence of falls among older outpatients during the COVID-19 pandemic in Vietnam. Management of factors associated with falls may be needed to reduce the burden of falls in the older population.

Objective To investigate the prevalence and factors associated with frailty in rural and urban older outpatients in Vietnam. Methods This cross‐sectional study included 1084 outpatients (aged ≥60 years; mean age 71.7 ± 7.4 years; female 65%) from rural (n = 600) and urban (n = 484) geriatric clinics from December 2019 to July 2020. Frailty was assessed using Fried frailty phenotype. Factors associated with frailty were assessed using logistic regression. Results Overall, frailty prevalence was 28% (rural, 26%; urban, 30%; p = 0.220). Factors associated with frailty were older age (odds ratio [OR] 1.16, 95% confidence interval [CI] 1.13–1.20, p < 0.001), being underweight (OR 1.88, 95% CI 1.10–3.27, p = 0.025) and limitations in activities of daily living (ADLs) (OR 6.04, 95% CI 1.63–22.41, p = 0.007) and instrumental ADLs (OR 5.83, 95% CI 3.74–9.08, p < 0.001). Higher education (OR 0.47, 95% CI 0.29–0.76, p = 0.002) and productive work (OR 0.39, 95% CI 0.21–0.71, p = 0.002) were protective factors against frailty. Conclusions In Vietnam, the prevalence of frailty in older outpatients was 28%, though not significantly different between urban and rural areas. Older age, being underweight and limitations in functional status can increase the odds of frailty, but higher education and productive work can reduce the odds of frailty.