Epidemiological characteristics of patients with Hutchinson-Gilford progeria syndrome and progeroid laminopathies in China.

BACKGROUND: Hutchinson-Gilford progeria syndrome (HGPS) and progeroid laminopathies (PL) are extremely rare genetic diseases with extremely poor prognoses. This study aims to investigate the epidemiological and genotypic characteristics of patients with HGPS/PL in China. METHODS: Using a cross-sectional study design, general characteristics and genotypic data of 46 patients with HGPS/PL from 17 provinces in China were analyzed. RESULTS: Among the 46 patients with HGPS/PL, 20 patients are HGPS, and the rest are PL; the identified total prevalence of HGPS/PL is 1/23 million. Among 42 patients with gene reports, 3 carried compound heterozygous mutations in the ZMPSTE24 while the other 39 carried LMNA mutations. Among PL, LMNA c.1579 C > T homozygous mutation was the most common. The onset of classic genotype HGPS is skin sclerosis in the first month after birth. The primary clinical manifestations of PL patients include skin abnormalities, growth retardation, and joint stiffness. The median age of onset for PL was 12 (6,12) months. CONCLUSIONS: In China, the identified total prevalence of HGPS/PL is 1/23 million. 92.8% of the genetic mutations of HGPS/PL were located in LMNA, and the rest in ZMPSTE24. Most patients of HGPS/PL have skin abnormalities as the earliest manifestation. Compared to PL, the classic genotype HGPS starts earlier. IMPACT STATEMENT: Hutchinson-Gilford progeria syndrome (HGPS) and progeroid laminopathies (PL) are extremely rare genetic diseases with extremely poor prognoses. To date, there is a paucity of epidemiological data related to HGPS/PL in China. This study first examined the genotypic, phenotypic, and prevalence characteristics of 40-50% of the cases of HGPS/PL in mainland China through a collaborative international registry effort. In China, the identified total prevalence of HGPS/PL is 1/23 million. 92.8% of the genetic mutations of HGPS/PL are located in LMNA. LMNA c.1579 C > T homozygous mutations are the most common form of gene mutations among the Chinese PL population.

Advances in imaging techniques to assess kidney fibrosis.

As a sign of chronic kidney disease (CKD) progression, renal fibrosis is an irreversible and alarming pathological change. The accurate diagnosis of renal fibrosis depends on the widely used renal biopsy, but this diagnostic modality is invasive and can easily lead to sampling error. With the development of imaging techniques, an increasing number of noninvasive imaging techniques, such as multipara meter magnetic resonance imaging (MRI) and ultrasound elastography, have gained attention in assessing kidney fibrosis. Depending on their ability to detect changes in tissue stiffness and diffusion of water molecules, ultrasound elastography and some MRI techniques can indirectly assess the degree of fibrosis. The worsening of renal tissue oxygenation and perfusion measured by blood oxygenation level-dependent MRI and arterial spin labeling MRI separately is also an indirect reflection of renal fibrosis. Objective and quantitative indices of fibrosis may be available in the future by using novel techniques, such as photoacoustic imaging and fluorescence microscopy. However, these imaging techniques are susceptible to interference or may not be convenient. Due to the lack of sufficient specificity and sensitivity, these imaging techniques are neither widely accepted nor proposed by clinicians. These obstructions must be overcome by conducting technology research and more prospective studies. In this review, we emphasize the recent advancement of these noninvasive imaging techniques and provide clinicians a continuously updated perspective on the assessment of kidney fibrosis.

Renoprotection with sodium-glucose cotransporter-2 inhibitors in children: Knowns and unknowns.

Sodium-glucose cotransporter-2 (SGLT2) inhibitors represent novel hypoglycemic drugs for the treatment of adult diabetes that have shown considerable potential for cardioprotection and renoprotection. This new drug can inhibit SGLT2 at the proximal tubule, increase glucosuria and natriuresis, and thus decreases the serum glucose level and blood pressure. Furthermore, the tubuloglomerular feedback activated by the natriuresis can decrease glomerular hyperfiltration, acknowledged as the main foundation of renoprotection. Several studies have confirmed the protective effects of SGLT2 inhibitors on the kidneys of adult diabetic patients and those with non-diabetic nephropathy; however, limited researches are seen in paediatric patients. In this review, we have summarized the mechanisms of action of SGLT2 inhibitors, the current experiences in adults, results of exploratory studies in children, and adverse events & obstacles of paediatric use. We further explore the potential and possible future research direction of SGLT2 inhibitors in paediatric diseases.