Unveiling the enigma of acute kidney disease: predicting prognosis, exploring interventions, and embracing a multidisciplinary approach

( Szu-yu Pan ),( Thomas Tao-min Huang ),( Zheng-hong Jiang ),( Li-chun Lin ),( I-jung Tsai ),( Tsung-lin Wu ),( Chih-yi Hsu ),( Ting Wang ),( Hui-chuen Chen ),( Yu-feng Lin ),( Vin-cent Wu ) 대한신장학회 2024 Kidney Research and Clinical Practice Vol.43 No.4

Acute kidney disease (AKD) is a critical transitional period between acute kidney injury and chronic kidney disease. The incidence of AKD following acute kidney injury is approximately 33.6%, and it can occur without identifiable preceding acute kidney injury. The development of AKD is associated with increased risks of chronic kidney disease, dialysis, and mortality. Biomarkers and subphenotypes are promising tools to predict prognosis in AKD. The complex clinical situations in patients with AKD necessitate a comprehensive and structured approach, termed “KAMPS” (kidney function check, advocacy, medications, pressure, sick day protocols). We introduce “MAND-MASS,” an acronym devised to summarize the reconciliation of medications during episodes of acute illness, as a critical component of the sick day protocols at AKD. A multidisciplinary team care, consisting of nephrologists, pharmacists, dietitians, health educators, and nurses, is an optimal model to achieve the care bundle in KAMPS. Although the evidence for patients with AKD is still lacking, several potential pharmacological agents may improve outcomes, including but not limited to angiotensin-converting enzyme inhibitors, angiotensin receptor blockers, mineralocorticoid receptor antagonists, sodium-glucose cotransporter 2 inhibitors, and glucagon-like peptide 1 receptor agonists. In conclusion, accurate prognosis prediction and effective treatment for AKD are critical yet unmet clinical needs. Future studies are urgently needed to improve patient care in this complex and rapidly evolving field.

Pleotropic effects of hypoxia-inducible factor-prolyl hydroxylase domain inhibitors: are they clinically relevant?

Chou Yu-Hsiang,Pan Szu-Yu,Lin Shuei-Liong 대한신장학회 2023 Kidney Research and Clinical Practice Vol.42 No.1

Anemia is common in patients with chronic kidney disease (CKD) and is mainly caused by insufficient production of erythropoietinfrom fibrotic kidney. Because anemia impairs quality of life and overall prognosis, recombinant human erythropoietin-related products(erythropoiesis-stimulating agents, ESAs) have been developed to increase hemoglobin level for decades. However, many safety concernshave been announced regarding the use of ESAs, including an increased occurrence of cardiovascular events, vascular accessthrombosis, cancer progression, and recurrence. Hypoxia-inducible factor (HIF) is crucial to erythropoietin production, as a result, prolylhydroxylase domain (PHD) enzyme inhibitors have been new therapeutic agents for the treatment of anemia in CKD. They can beadministered orally, which is a preferred route for patients not undergoing hemodialysis. In clinical trials, PHD inhibitor could inducenoninferior effect on erythropoiesis and improve functional iron deficiency compared with ESAs. Although no serious adverse eventswere reported, safety is still a concern because HIF stabilization induced by PHD inhibitor has pleotropic effects, such as angiogenesis,metabolic change, and cell survival, which might lead to unwanted deleterious effects, including fibrosis, inflammation, cardiovascularrisk, and tumor growth. More molecular mechanisms of PHD inhibition and long-term clinical trials are needed to observe thesepleotropic effects for the confirmation of safety and efficacy of PHD inhibitors.

Comparison of the Infant and Adult Adipose-Derived Mesenchymal Stem Cells in Proliferation, Senescence, Anti-oxidative Ability and Differentiation Potential

Wu Szu-Hsien,Yu Jin-Huei,Liao Yu-Ting,Liu Kuo-Hao,Chiang En-Rung,Chang Ming-Chau,Wang Jung-pan 한국조직공학과 재생의학회 2022 조직공학과 재생의학 Vol.19 No.3

BACKGROUND: Infant adipose-derived mesenchymal stem cells (ADSCs) collected from excised polydactyly fat tissue, which was surgical waste, could be cultured and expanded in vitro in this study. In addition, the collecting process would not cause pain in the host. In this study, the proliferation, reduction of senescence, anti-oxidative ability, and differentiation potential in the infant ADSCs were compared with those in the adult ADSCs harvested from thigh liposuction to determine the availability of infant ADSCs. METHODS: Proliferation was determined by detecting the fold changes in cell numbers and doubling time periods. Senescence was analyzed by investigating the age-related gene expression levels and the replicative stress. The superoxide dismutase (SOD) gene expression, adipogenic, neurogenic, osteogenic, and tenogenic differentiation were compared by RTqPCR. The chondrogenic differentiation efficiency was also determined using RT-qPCR and immunohistochemical staining. RESULTS: The proliferation, SOD (SOD1, SOD2 and SOD3) gene expression, the stemness-related gene (c-MYC) and telomerase reverse transcriptase of the infant ADSCs at early passages were enhanced compared with those of the adults’. Cellular senescence related genes, including p16, p21 and p53, and replicative stress were reduced in the infant ADSCs. The adipogenic genes (PPARc and LPL) and neurogenic genes (MAP2 and NEFH) of the infant ADSC differentiated cells were significantly higher than those of the adults’ while the expression of the osteogenic genes (OCN and RUNX) and tenogenic genes (TNC and COL3A1) of both demonstrated opposite results. The chondrogenic markers (SOX9, COL2 and COL10) were enhanced in the infant ADSC differentiated chondrogenic pellets, and the expression levels of SODs were decreased during the differentiation process. CONCLUSION: Cultured infant ADSCs demonstrate less cellular senescence and replicative stress, higher proliferation rates, better antioxidant defense activity, and higher potential of chondrogenic, adipogenic and neurogenic differentiation.

Biomarkers in pursuit of precision medicine for acute kidney injury: hard to get rid of customs

( Kun-mo Lin ),( Ching-chun Su ),( Jui-yi Chen ),( Szu-yu Pan ),( Min-hsiang Chuang ),( Cheng-jui Lin ),( Chih-jen Wu ),( Heng-chih Pan ),( Vin-cent Wu ) 대한신장학회 2024 Kidney Research and Clinical Practice Vol.43 No.4

Traditional acute kidney injury (AKI) classifications, which are centered around semi-anatomical lines, can no longer capture the complexity of AKI. By employing strategies to identify predictive and prognostic enrichment targets, experts could gain a deeper comprehension of AKI’s pathophysiology, allowing for the development of treatment-specific targets and enhancing individualized care. Subphenotyping, which is enriched with AKI biomarkers, holds insights into distinct risk profiles and tailored treatment strategies that redefine AKI and contribute to improved clinical management. The utilization of biomarkers such as N-acetyl-β-D-glucosaminidase, tissue inhibitor of metalloprotease-2·insulin-like growth factor-binding protein 7, kidney injury molecule-1, and liver fatty acid-binding protein garnered significant attention as a means to predict subclinical AKI. Novel biomarkers offer promise in predicting persistent AKI, with urinary motif chemokine ligand 14 displaying significant sensitivity and specificity. Furthermore, they serve as predictive markers for weaning patients from acute dialysis and offer valuable insights into distinct AKI subgroups. The proposed management of AKI, which is encapsulated in a structured flowchart, bridges the gap between research and clinical practice. It streamlines the utilization of biomarkers and subphenotyping, promising a future in which AKI is swiftly identified and managed with unprecedented precision. Incorporating kidney biomarkers into strategies for early AKI detection and the initiation of AKI care bundles has proven to be more effective than using care bundles without these novel biomarkers. This comprehensive approach represents a significant stride toward precision medicine, enabling the identification of high-risk subphenotypes in patients with AKI.