Comorbidities as Risk Factors for Severe Disease in Hospitalized Elderly COVID-19 Patients by Different Age-Groups in Japan

<b><i>Introduction:</i></b> Old age is an independent risk factor (RF) for severe COVID-19; evidence for clinico-epidemiological characteristics among elderly COVID-19 patients is scarce. We aimed to analyze clinical and epidemiological characteristics and comorbidities associated with COVID-19 inpatients in age-stratified populations of an elderly COVID-19 cohort. <b><i>Methods:</i></b> We conducted a retrospective cohort study, using nationwide registry data of COVID-19 patients hospitalized before October 31, 2020 (major information entered in the registry as of December 28, 2020). Participants were divided by age according to the Japan Geriatrics Society and the Japan Gerontological Society: pre-old (65–74 years), old (75–89 years), and super-old (≥90 years). Multivariable logistic regression (MLR) analyses were conducted to identify stratified risk and relationships with comorbidities associated with worse outcomes in different age-groups of elderly patients. Demographics and supportive care were evaluated by category. <b><i>Results:</i></b> Data of 4,701 patients from 444 hospitals were included. Most patients (79.3%) had at least one comorbidity; the proportion of patients with hypertension was high in all categories. The proportion of patients with dementia, cardiovascular disease, and cerebrovascular disease increased with age. The percentage of patients who underwent invasive mechanical ventilation/extracorporeal membrane oxygenation was lower in the super-old group. In total, 11.5% of patients died (5.3%, pre-old; 15.2%, old; and 22.4%, super-old). MLR showed that the risk of critical illness differed among age-groups. Male sex was a significant RF in all ages. Collagen disease, moderate to severe renal disorder, and dialysis were significant RFs in older patients, while hematological malignancies and metastatic tumors were more important RFs for severe disease in relatively younger patients. Most of the RFs for critical illnesses were associated with death. <b><i>Conclusion:</i></b> Differences in the epidemiological and clinical characteristics among the different age-groups were found.

A New Genetic Insight for Orphan Renal Disorder, Fabry: A Review

Fabry is the rare X-linked genetic disorder caused due to mutation in Alpha –Galactosidase encoding GLA gene mutation in chromosome number 22. It has wide diversification in prevalence due to clinical heterozygosity. There are some potential biomarkers for the evaluation of normal or altered genes responsible for Fabry. Advances in the research of biomarkers over the years have made significant development for several clinical indicators, viz. urine-derived cells, oxidative stress, DNA methylation, etc. At present days the recommended therapies for the disease are Enzyme Replacement Therapy (ERT), Chaperone therapy (CT), and mRNA-based therapy, besides, some second-generation therapies which are still under clinical trials.

Nephrotonic and Nephroprotective medicinal herbs in traditional Persian Medicine: Review and assessment of scientific evidence

: The tendency to use herbal and complementary therapies has been increased dramatically in last decades. The aim of this study is reviewing nephrotonic and nephroprotective medicinal herbs in traditional Persian Medicine (TPM) historical books, and assessment of relevant scientific evidence and possible mechanisms of action. In this study, seven major references among pharmaceutical books of PM from the 11th to 19th centuries were selected and were searched with key words equivalent to “nephroprotection”. To find new studies, the scientific name of medicinal herbs which were repeated twice or more were searched using data bases including PubMed, and Google scholar with keywords of nephroprotective, renal disorder, renal failure and kidney. Also, probable effective mechanisms were explored with key words including oxidative stress, antioxidant, inflammation, anti-inflammatory and angiotensin-converting-enzyme inhibitor. 210 herbal remedies were found with kidney strengthening, nephroprotective, and atrophy prevention effects in reviewed books. The most repeated herbs were 41 Results of scientific evidence showed that the possible functional mechanisms of these plants include anti-inflammatory, anti-oxidative, blood pressure/glucose-lowering effect as well as improvement of glomerular filtration, prevention of tissue damage, and enhancing the reconstructive power of cells. The list of medicinal herbs in this study can be used as a base of future studies on production of new medicines for prevention or treatment of renal failure and for the enhancement of renal performance.

A new atypical splice mutation of PKD2 leading to autosomal dominant polycystic kidney disease in a Chinese family

Introduction: Autosomal dominant polycystic kidney disease (ADPKD) is a very common hereditary renal disorder. Mutations in PKD1 and PKD2, identified as disease-causing genes, cause about 85% and 15% of ADPKD cases, respectively. Methods: In this study, the mutation analysis of PKD genes was implemented in a Chinese family with suspected ADPKD using targeted clinical exome sequencing (CES). The candidate pathogenic variants were further tested by using Sanger sequencing and validated for co-segregation. In addition, reverse transcription-polymerase chain reaction (RT-PCR) was performed to test abnormal splicing and assess its potential pathogenicity. Results: A novel atypical splicing mutation which belongs to unclassified variants (UCVs), IVS6+5G>C, was identified in three family members by CES and was shown to co-segregate only with the affected individuals. RT-PCR reveals the abnormal splicing of exon 6, thus to cause truncating mutation. These findings suggest that the atypical splice site alteration, IVS6+5G>C, in the PKD2 gene is the potential pathogenic mutation leading to ADPKD in the Chinese family. Conclusion: The data available in this study provided strong evidence that IVS6+5G>C is the potential pathogenic mutation for ADPKD. Meantime, this case also emphasizes the significance of functional analysis of UCVs and genotype-phenotype correlation in ADPKD.

Uremic Stomatitis: A Case Report

Uremic stomatitis is a rarely reported oral mucosal disorder associated with renal disorder. It is mostly seen in cases of end stage renal disease or undiagnosed or untreated chronic renal failure. Its frequency has diminished due to the advent of renal dialysis. Clinically uremic stomatitis is characterised by the presence of painful plaques and crusts that are usually distributed on the buccal and labial mucosa, dorsal or ventral surface of the tongue, gingiva and the floor of the mouth. Ultimate treatment consists of improvement of blood urea concentration and underlying renal failure is supported by enhancement of oral hygiene with antiseptic mouthwashes and antimicrobial/ antifungal agents, if necessary. Here we report a case of a 50 year old Male patient who reported to the department with the complaint of inability to open mouth due to ulcers present intra-orally, who was a kidney patient undergoing dialysis, who was then treated with topical steroid and antifungal medications with follow up made once in a week.

Ppia is the most stable housekeeping gene for qRT-PCR normalization in kidneys of three Pkd1-deficient mouse models

Autosomal Dominant Polycystic Kidney Disease (ADPKD) is the most common inherited renal disorder, characterized by renal cyst development leading to end-stage renal disease. Although the appropriate choice of suitable reference is critical for quantitative RNA analysis, no comparison of frequently used “housekeeping” genes is available. Here, we determined the validity of 7 candidate housekeeping genes (Actb, Actg1, B2m, Gapdh, Hprt, Pgam1 and Ppia) in kidney tissues from mouse models orthologous to ADPKD, including a cystic mice (CY) 10–12 weeks old (Pkd1flox/flox:Nestincre/Pkd1flox/−:Nestincre, n = 10) and non-cystic (NC) controls (Pkd1flox/flox/Pkd1flox/-, n = 10), Pkd1-haploinsufficient (HT) mice (Pkd1+/−, n = 6) and wild-type (WT) controls (Pkd1+/+, n = 6) and a severely cystic (SC) mice 15 days old (Pkd1V/V, n = 7) and their controls (CO, n = 5). Gene expression data were analyzed using six distinct statistical softwares. The estimation of the ideal number of genes suggested the use of Ppia alone as sufficient, although not ideal, to analyze groups altogether. Actb, Hprt and Ppia expression profiles were correlated in all samples. Ppia was identified as the most stable housekeeping gene, while Gapdh was the least stable for all kidney samples. Stat3 expression level was consistent with upregulation in SC compared to CO when normalized by Ppia expression. In conclusion, present findings identified Ppia as the best housekeeping gene for CY + NC and SC + CO groups, while Hprt was the best for the HT + WT group.

Catechins: Therapeutic Perspectives in COVID-19-Associated Acute Kidney Injury

Data obtained from several intensive care units around the world have provided substantial evidence of the strong association between impairment of the renal function and in-hospital deaths of critically ill COVID-19 patients, especially those with comorbidities and requiring renal replacement therapy (RRT). Acute kidney injury (AKI) is a common renal disorder of various etiologies characterized by a sudden and sustained decrease of renal function. Studies have shown that 5–46% of COVID-19 patients develop AKI during hospital stay, and the mortality of those patients may reach up to 100% depending on various factors, such as organ failures and RRT requirement. Catechins are natural products that have multiple pharmacological activities, including anti-coronavirus and reno-protective activities against kidney injury induced by nephrotoxic agents, obstructive nephropathies and AKI accompanying metabolic and cardiovascular disorders. Therefore, in this review, we discuss the anti-SARS-CoV-2 and reno-protective effects of catechins from a mechanistic perspective. We believe that catechins may serve as promising therapeutics in COVID-19-associated AKI due to their well-recognized anti-SARS-CoV-2, and antioxidant and anti-inflammatory properties that mediate their reno-protective activities.

Proteomics to Metabolomics: A New Insight Into the Pathogenesis of Hypertensive Nephropathy

Background Hypertensive nephropathy (HN) is a high burden disorder and a leading cause of end-stage renal disorder. In spite of huge investigations, the underlying mechanisms are yet largely unknown. Systems biology is a promising approach to provide a comprehensive insight towards this complex disorder. Methods Protein expression profiles of kidney tubule and cortex sub-compartments were retrieved from the PRIDE database and the quality of the datasets were assessed using principal component analysis (PCA) and hierarchical clustering. Differentially expressed proteins (DEPs) were detected and their attributed metabolites were enriched and their interactions were assessed in multi-layer networks. Moreover, considering the DEPs and the predicted metabolites, key biomedical phenomena with a leading role in HN pathogenesis were proposed. Results Amino acid and purine metabolisms are the most prominent alteration in kidney cortex whereas dysregulation of energy hemostasis is a key pathogenic mechanism in tubule. Besides, actin cytoskeleton disorganization is an enriched pathway in both anatomical areas. Conclusion The proteomics profiles of kidney sub-compartments were analyzed using a top-down approach to infer the main pathogenic processes. The constructed holistic map of HN can be exploited to propose novel therapeutic strategies.