Asghar, Muhammad S

ABSTRACT Chronic changes on kidney biopsy specimens include increasing amounts of arteriosclerosis, glomerulosclerosis, interstitial fibrosis and tubular atrophy, enlarged nephron size, and reduced nephron number. These chronic changes are difficult to accurately assess by visual inspection but are reasonably quantified using morphometry. This review describes the various patient populations that have undergone morphometric analysis of kidney biopsies. The common approaches to morphometric analysis are described. The chronic kidney disease outcomes associated with various chronic changes by morphometry are also summarized. Morphometry enriches the characterization of chronicity on a kidney biopsy and this can supplement the pathologist's diagnosis. Artificial intelligence image processing tools are needed to automate the annotations needed for practical morphometric analysis of kidney biopsy specimens in routine clinical care.

The coronavirus disease-2019 (COVID-19) infection has taken the world by storm within a few months. Evidence has suggested that patients with electrolyte imbalances at baseline may have a longer duration of hospital stay. We aimed to determine the factors associated with hyponatremia on admission in COVID-19 patients and its impact on the length of stay. We conducted a retrospective study including 521 patients who tested positive for COVID-19 and had their electrolytes checked on admission from June 2020 to October 2020. Patients with sodium <135 mmol/l were included in the hyponatremic group and were compared against normonatremic patients. The severity of COVID-19 was found to be more prevalent in the case group as compared to control (38.3% vs 29.2%; 21.1% vs 17.7%). Hyponatremic patients stayed more than 5 days in hospital (56.3% vs 46.5%), and stayed longer in special care (23.4% vs 20.0%) as compared to controls. Hyponatremic patients as compared to control were more likely to have diabetes (47.9% vs 30.0%), hypertension (49.0% vs 38.5%), ischemic heart disease (20.7% vs 15.4%), chronic liver disease (2.7% vs 1.2%), and chronic kidney disease (9.6% vs 3.8%). Upon matching on the age, the adjusted odds of hyponatremia in COVID-19-positive patients were 1.9 times among diabetic patients. Moreover, COVID-19-positive patients suffering from CKD had a higher risk of developing hyponatremia (OR = 2.3, 95% CI: 1.1–5.6). The risk of hyponatremia among COVID-19-positive patients is statistically higher in patients with 1 comorbidity (OR = 1.9, 95%CI: 1.3–3.4). Hyponatremia on admission can be used to forecast the length of hospital stay and the severity of illness in COVID-19 patients.

Background: Soluble urokinase plasminogen activator receptor (suPAR) is an inflammatory biomarker that is used to predict mortality, readmission, early discharge, and LOS, thus, serves as a useful tool for ED physicians. Our study aims to analyze the efficacy of suPAR in predicting these prognostic markers in ED. Methods: We performed a comprehensive search on 6 databases from the inception to 30th November 2022, to select the following eligibility criteria; a) observation or triage trial studies investigating the role of suPAR levels in predicting: 30 day and 90-day mortality, 30-day readmission, early discharge (within 24hr), and LOS in patients coming to AMU. Results: A total of 13 studies were included, with a population size of 35,178, of which 52.9% were female with a mean age of 62.93 years. Increased risk of 30-day mortality (RR = 10.52; 95% CI = 4.82–22.95; I2 = 38%; P < .00001), and risk of 90-day mortality (RR = 5.76; 95% CI = 3.35–9.91; I2 = 36%; P < .00001) was observed in high suPAR patients. However, a slightly increased risk was observed for 30-day readmission (RR = 1.50; 95% CI = 1.16–1.94; I2 = 54%; P = .002). More people were discharged within 24hr in the low suPAR level group compared to high suPAR group (RR = 0.46; 95% CI = 0.40–0.53; I2 = 41%; P < .00001). LOS was thrice as long in high suPAR level patients than in patients with low suPAR (WMD = 3.20; 95% CI = 1.84–4.56; I2 = 99%; P < .00001). Conclusion: suPAR is proven to be a significant marker in predicting 30-day and 90-day mortality in ED patients.

Abstract Aim Type 1 diabetes mellitus is widely recognized as a chronic autoimmune disease characterized by the pathogenic destruction of beta cells, resulting in the loss of endogenous insulin production. Insulin administration remains the primary therapy for symptomatic treatment. Recent studies showed that disease‐modifying agents, such as anti‐CD3 monoclonal antibodies, have shown promising outcomes in improving the management of the disease. In late 2022, teplizumab received approval from the US Food and Drug Administration (FDA) as the first disease‐modifying agent for the treatment of type 1 diabetes. This review aims to evaluate the clinical evidence regarding the efficacy of anti‐CD3 monoclonal antibodies in the prevention and treatment of type 1 diabetes. Methods A comprehensive search of PubMed, Google Scholar, Scopus and Cochrane Central Register of Controlled Trials (CENTRAL) was conducted up to December 2022 to identify relevant randomized controlled trials. Meta‐analysis was performed using a random‐effects model, and odds ratios with 95% confidence intervals (CIs) were calculated to quantify the effects. The Cochrane risk of bias tool was employed for quality assessment. Results In total, 11 randomized controlled trials involving 1397 participants (908 participants in the intervention arm, 489 participants in the control arm) were included in this review. The mean age of participants was 15 years, and the mean follow‐up time was 2.04 years. Teplizumab was the most commonly studied intervention. Compared with placebo, anti‐CD3 monoclonal antibody treatment significantly increased the C‐peptide concentration in the area under the curve at shorter timeframes (mean difference = 0.114, 95% CI: 0.069 to 0.159, p = .000). Furthermore, anti‐CD3 monoclonal antibodies significantly reduced the patients' insulin intake across all timeframes (mean difference = −0.123, 95% CI: −0.151 to −0.094, p < .001). However, no significant effect on glycated haemoglobin concentration was observed. Conclusion The findings of this review suggest that anti‐CD3 monoclonal antibody treatment increases endogenous insulin production and improves the lifestyle of patients by reducing insulin dosage. Future studies should consider the limitations, including sample size, heterogeneity and duration of follow‐up, to validate the generalizability of these findings further.

Significance Statement Nephrosclerosis (glomerulosclerosis, interstitial fibrosis, and tubular atrophy) is the defining pathology of both kidney aging and CKD. Optimal thresholds for nephrosclerosis that identify persons with a progressive disease are unknown. This study determined a young-age threshold (18–29 years) and age-based 95th percentile thresholds for nephrosclerosis on the basis of morphometry of kidney biopsy sections from normotensive living kidney donors. These thresholds were 7.1-fold to 36-fold higher in older (70 years or older) versus younger (aged 18–29 years) normotensive donors. Age-based thresholds, but not young-age threshold, were prognostic for determining risk of progressive CKD among patients who underwent a radical nephrectomy or a for-cause native kidney biopsy, suggesting that age-based thresholds are more useful than a single young-age threshold for identifying CKD on biopsy. Background Nephrosclerosis, defined by globally sclerotic glomeruli (GSG) and interstitial fibrosis and tubular atrophy (IFTA), is a pathology of both kidney aging and CKD. A comparison of risk of progressive CKD using aged-based thresholds for nephrosclerosis versus a single young-adult threshold is needed. Methods We conducted morphometric analyses of kidney biopsy images for %GSG, %IFTA, and IFTA foci density among 3020 living kidney donors, 1363 patients with kidney tumor, and 314 patients with native kidney disease. Using normotensive donors, we defined young-age thresholds (18–29 years) and age-based (roughly by decade) 95th percentile thresholds. We compared age-adjusted risk of progressive CKD (kidney failure or 40% decline in eGFR) between nephrosclerosis that was “normal compared with young,” “normal for age but abnormal compared with young,” and “abnormal for age” in patients with tumor and patients with kidney disease. Results The 95th percentiles in the youngest group (18–29 years) to the oldest group (70 years or older) ranged from 1.7% to 16% for %GSG, 0.18% to 6.5% for %IFTA, and 8.2 to 59.3 per cm 2 for IFTA foci density. Risk of progressive CKD did not differ between persons with nephrosclerosis “normal compared with young” versus “normal for age but abnormal compared with young.” Risk of progressive CKD was significantly higher with %GSG, %IFTA, or IFTA foci density that was abnormal versus normal for age in both cohorts. Conclusions Given that increased risk of progressive CKD occurs only when nephrosclerosis is abnormal for age, age-based thresholds for nephrosclerosis seem to be better than a single young-age threshold for identifying clinically relevant CKD.