Kidney Diseases

Li, Jing; Haase, Volker H.; Hao, Chuan-Ming

doi: 10.1159/000527835pmid: 36756084

Background: Anemia is a common complication of chronic kidney disease. The hypoxia-inducible factor prolyl hydroxylase inhibitor (HIF-PHI) is a new class of oral drugs for the treatment of renal anemia. Summary: Clinical trials have consistently shown that HIF-PHIs can effectively increase hemoglobin in both the dialysis population and the nondialysis population. The effects of HIF-PHIs in treating renal anemia include promoting endogenous erythropoietin production and facilitating iron mobilization. Several studies suggest that the erythropoiesis effect of roxadustat is less affected by inflammation. Careful monitoring of thromboembolic events and tumor before and during HIF-PHI treatment is necessary. Key Messages: HIF-PHIs are effective in correcting renal anemia. The long-term safety of HIF-PHIs needs to be further studied.

Liu, Wenyu; Yu, Shengqiang

doi: 10.1159/000528066pmid: 36756081

Background: Mineralocorticoid receptor antagonists (MRAs) protect cardiorenal function by robust anti-inflammatory and antifibrotic functions beyond classical functions of maintaining fluid and electrolyte homeostasis. The application of traditional steroidal MRAs to chronic kidney disease (CKD) has been limited by adverse events, especially when combined with renin-angiotensin system inhibitors, guideline-recommend drugs for CKD patients. Recently, the development of nonsteroidal MRAs gives patients with CKD a promising option. Summary: The discovery of nonsteroidal MRAs is based on the molecular structure of the mineralocorticoid receptor (MR) and differs in structure from spironolactone, a progesterone derivative. The structure of nonsteroidal MRAs determines their more effective and selective inhibition of MR providing patients more benefits with fewer adverse effects than MRAs. Recently, two types of nonsteroidal MRAs, finerenone and esaxerenone, have been authorized for clinical use. We elaborate on the physiological and pathophysiological mechanisms of MR, review the history of MRAs, compare two generations of MRAs, and introduce the forward clinical trials of finerenone and esaxerenone. Key Messages: Finerenone reduces the cardiovascular and kidney composite outcomes in diabetic patients with CKD eliciting a cardiorenal protection effect. Esaxerenone can effectively reduce blood pressure in hypertensive patients and albuminuria in diabetic patients with CKD. The risk of hyperkalemia is controllable and acceptable through the serum potassium-based dose titrate. Combination therapy with sodium-glucose cotransport-2 inhibition or a new potassium binder may be a safer and more efficient approach.

Syeda, Madiha Zahra; Hong, Tu; Zhang, Chao; Ying, Songmin; Shen, Huahao

doi: 10.1159/000528156pmid: 36756082

Background: Since their discovery, around 150 years, eosinophils research has been a field of changing perspective, and new directions are emerging since then. Summary: Initially, eosinophils were perceived as terminally differentiated cytotoxic effector cells. Clearly, eosinophils are capable of playing functions other than immune responses, which is not surprising given their intricate interactions with pathogens as well as other circulating leukocytes. Attempts to comprehend the eosinophil biology and functions have yielded remarkable insights into their roles in human health and sickness. The use of FDA-approved eosinophils-targeting biologics has provided exciting opportunities to directly explore the contributions of eosinophils in disease etiology in humans. Key Messages: In this review, we will focus on the eosinophils’ lifecycle and discuss the current state of knowledge from mouse models and retrospective human studies demonstrating eosinophils’ roles in the pathogenesis of human diseases such as asthma, cancer, and kidney disorders. Despite three recently approved anti-eosinophil agents, a number of key questions and challenges remain far from settled, thereby generating opportunity to further explore this enigmatic cell. A comprehensive understanding of eosinophils biology and function will surely aid in developing improved therapeutic strategies against eosinophils-associated disorders.

Montgomerie, Christina; Spaak, Jonas; Evans, Marie; Jacobson, Stefan H.

doi: 10.1159/000527299pmid: 36756083

Introduction: Complex integrated information on disease mechanisms and in-hospital outcomes in mild to moderate acute kidney injury (AKI) is scarce. Methods: The Stockholm Prospective AKI Cohort Study (SAKIS) included all patients (≥18 years, n = 1,519) with community-acquired AKI (KDIGO criteria) admitted to the nephrology ward at Danderyd University Hospital, Stockholm, Sweden, between 2009 and 2018. Detailed laboratory measures were registered. Odds ratio for hypo- and hyperkalemia, recovery of kidney function by 30% and 50%, and in-hospital mortality were assessed by logistic regression analysis. Results: Factors independently associated with the presence of hyperkalemia at admission were high age, high serum creatinine (sCr), and low C-reactive protein (CRP). Signs of malnutrition, inflammation, and acidosis were seen in 31% of patients. Kidney recovery, defined as a reduction of sCr by 30% in-hospital (63% of all patients), was associated with higher age, female sex, lower body mass index (BMI), higher hemoglobin, and higher CRP. Factors independently associated with mortality (4.4% of patients) were high age, high BMI, and low albumin. Conclusion: This study provides a detailed description of community-acquired AKI and comprehensive analyses of integrated clinical and laboratory data associated with kidney recovery. Features related to anemia, albuminuria, malnutrition, inflammation, and acidosis associate with partial or moderate short-term recovery of kidney function, with disturbances in potassium homeostasis, and with in-hospital mortality. Future studies are warranted to analyze the long-term consequences of AKI in terms of risk of kidney failure, cardiovascular morbidity, and mortality.

Wang, Qin; Wang, Yu; Yang, Chao; Wang, Jinwei; Shi, Ying; Wang, Haibo; Zhang, Luxia; Zhao, Ming-Hui

doi: 10.1159/000527967pmid: 36756086

Introduction: The aim of this study was to explore the chronological trends in clinical features and utilization of healthcare resources for hospitalized patients with urolithiasis in China. Methods: Patients with urolithiasis were extracted from the Hospital Quality Monitoring System, a national database of hospitalized patients in China, based on the International Classification of Diseases, Tenth Revision, codes. Variables including demographic characteristics, comorbidities, treatment modalities for urolithiasis, length of hospital stay, and expenditures were collected and analyzed. Results: Among 79.8 million hospitalized patients, 3.5 million were diagnosed with urolithiasis with an increasing trend (from 3.0% in 2013 to 4.0% in 2018). Most of these patients had upper urinary tract calculi (76.6% in 2013 and 81.7% in 2018). Middle-aged patients (46–65 years) constituted the largest proportion with a stable trend (from 46.9% in 2013 to 48.8% in 2018), while the proportion of older patients (>65 years) showed an increasing trend (from 23.7% in 2013 to 27.4% in 2018). The percentages of gout/hyperuricemia, hypertension, diabetes, and cardiovascular disease among the hospitalized patients with urolithiasis increased steadily, with the sharpest increases in patients from rural areas. Overall, 656,952 patients (18.9%) received surgical interventions for urolithiasis. The proportions of ureteroscopy and extracorporeal shockwave lithotripsy increased steadily during the 6-year study period, with simultaneous decreases in open surgery and percutaneous nephrolithotomy. The median length of hospital stay decreased from 10 days to 8 days. The cost of urolithiasis intervention accounted for 2.0% of the total hospitalization fee in 2013 and increased to 2.7% in 2018. Conclusions: The analysis showed an increasing trend in the percentage of hospitalized patients with urolithiasis, accompanied by an increased percentage of the total hospitalization fee for urolithiasis intervention during the 6-year study period. Based on the increasing trends in the proportion of older patients (>65 years) and percentages of metabolic comorbidities among patients with urolithiasis, an increased burden of urolithiasis on the healthcare system in China is anticipated.

Sun, Zhuo; Shao, Xiaotong; Wu, Haotian; Zhao, Yaxian; Cao, Yidan; Li, Danhua; Sun, Ying; Wang, Qingling

doi: 10.1159/000528010pmid: 36756085

Introduction: Phosphatase and tensin (PTEN) is a multifunctional gene associated with the normal development and physiological function of various tissues including the kidney. However, its role in renal tubular reabsorption function has not been well elucidated. Methods: We generated a renal tubule-specific Pten knockout mouse model by crossing Pten^fl/fl mice with Ksp-Cre transgenic mice, evaluated the effect of Pten loss on renal tubular function, and investigated the underlying mechanisms. Results: Pten loss resulted in abnormal renal structure and function and water retention in multiple organs. Our results also demonstrated that aquaporin-2 (AQP2), an important water channel protein, was upregulated and concentrated on the apical plasma membrane of collecting duct cells, which could be responsible for the impaired water balance in Pten loss mice. The regulation of Pten loss on AQP2 was mediated by protein kinase B (AKT) activation. Conclusions: Our results reveal a connection between PTEN gene inactivation and water retention, suggesting the importance of PTEN in normal kidney development and function.