Molecular Mechanisms Of Progression From Acute Kidney Injury To Acute Kidney Disease And Then To Chronic Kidney Disease

This article will provide a comprehensive overview of the molecular pathways involved in the transition from acute kidney injury (AKI) and acute kidney disease (AKD) to chronic kidney disease (CKD). The links between renal injury and the pathophysiological mechanisms of AKI and AKD are highlighted, including renal hypoperfusion, sepsis, nephrotoxicity, and immune responses. In addition, various molecules play key roles in inflammation and hypoxia, triggering maladaptive repair, mitochondrial dysfunction, immune system responses, and cellular senescence of renal cells. Key signaling pathways such as Wnt/β-catenin, TGF-β/SMAD, and Hippo/YAP/TAZ promote fibrosis and affect renal function. The renin-angiotensin-aldosterone system (RAAS) initiates a cascade leading to renal fibrosis, with aldosterone exacerbating oxidative stress and cellular changes, thereby promoting fibrosis. Clinical evidence suggests that RAS inhibitors can prevent CKD progression, especially after AKI, although more extensive trials are needed to confirm their full impact.

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Inflammation

Although AKI has been implicated in various mechanisms, it is primarily considered a complex clinical syndrome driven by a sudden illness with systemic effects [1]. After acute injury, stressed cells and damaged tissues may release damage-associated molecular patterns (DAMPs), which interact with pattern recognition receptors (PRRs) such as Toll-like receptor 4 (TLR4) to activate innate immune pathways, leading to the production of proinflammatory cytokines, chemokines, and reactive oxygen species (ROS), ultimately leading to further cell necrosis and tissue damage [2-3]. Intracellular molecules released by necrotic tubular cells, such as high-mobility group box 1 protein (HMGB1), histones, heat shock peptides, and fibrinogens, enter the extracellular space and aggravate the inflammatory cascade [4]. In addition, the continued release of inflammation-related fibrogenic cytokines, such as transforming growth factor β (TGF-β) and interleukin-13 (IL-13), can trigger epithelial-mesenchymal transition (EMT), which may lead to renal fibrosis and chronic renal failure [5]. The most prominent signaling pathways involved in the expression of inflammation-related genes include nuclear factor κB (NF-κB), mitogen-activated protein kinase (MAPK), and STAT pathway components. NF-κB is a key nuclear transcription factor that plays a critical role in regulating genes associated with inflammatory responses and in the release of proliferative inflammatory cytokines, chemokines, and adhesion factors. The NF-κB family consists of five related protein members: p50, p52, RelA (p65), RelB, and c-Rel. The inactivation of NF-κB is regulated by IκB kinase (IKK) [6]. IKK is phosphorylated and rapidly degraded in response to ROS and cytokines.

This process leads to the release of free NF-κB dimers, which are then phosphorylated and translocated to the nucleus. Subsequently, this translocation promotes the transcription of inflammation-related genes [7]. However, studies have shown that silent information regulated transcript 1 (SIRT1), also known as Sirtuin1, has the potential to mitigate renal damage [8]. SIRT1 is a histone deacetylase, and overexpression of SIRT1 in renal tubular epithelial cells (TECs) inhibits NF-κB activation. This inhibition occurs through deacetylation of the Lys310 residue on the RelA/p65 subunit or by reducing the activity of the acetyltransferase P300/CBP[9]. Therefore, the SIRT1 pathway provides a potential therapeutic target for alleviating AKI. Diosmin, a glycosylated polyphenolic flavonoid found in Citrus aurantium, alleviates renal fibrosis mainly through anti-inflammatory effects that rely on SIRT3-mediated NF-κB p65 nuclear expression[10]. In addition, targeted therapies that inhibit inflammatory processes in the context of kidney disease have also received attention. This includes regulating the NF-εB pathway and specifically inhibiting NF-κB/NLRP3 activity by regulating the NF-κB signaling pathway using microRNAs (miRNAs)[11].

Hypoxia

TECs rely on ATP in the mitochondrial respiratory chain through Na-K-ATPase to maintain renal function, a process that is highly dependent on oxygen. Hypoxia during AKI leads to mitochondrial dysfunction, increased ROS production, and endothelial damage, which further induce peritubular capillary rarefaction, exacerbate tissue hypoxia, and perpetuate this cycle [12]. Hypoxia has been shown to significantly increase miR-493, leading to the inhibition of the cell cycle regulator oncoprotein (stathmin-1, STMN-1). This induction leads to G2/M cell cycle arrest and the release of a large number of cytokines in vitro [13]. In addition, hypoxia-inducible factors (HIFs) are also involved in the development of renal fibrosis after AKI. Generally, HIF is composed of various subunits, including various α subunits (HIF1/2/3α) and shared HIF1β. Under normal physiological conditions, HIF-1α is hydroxylated by prolyl hydroxylase domain (PHD) proteins and then bound to the Von Hippel-Lindau (VHL) E3 ubiquitin ligase, followed by degradation in the proteasome [14]. Under hypoxic conditions, inhibition of PHD proteins leads to the translocation of HIF-1/2α into the nucleus, where it binds to HIF-1β and further initiates gene transcription, including the expression of vascular endothelial growth factor (VEGF), erythropoietin (EPO), and glucose transporter 1 (GLUT1) [15]. Whether HIF is a protective factor for renal fibrosis is still under debate. Some studies have shown that HIF is involved in regulating profibrotic genes and promoting renal fibrosis through the TGF-β, NF-κB, and phosphatidylinositol 3-kinase/protein kinase B (PI3K/Akt) pathways or through the G2/M cell cycle arrest pathway via p53 upregulation [16-17]. In contrast, some authors have found that under hypoxic conditions, HIF-1α binds to FoxO3, which is considered a renal protective factor after AKI, and subsequently inhibits the hydroxylation and degradation of FoxO3 [18]. SerpinA3K is another novel biomarker of the transition from AKI to CKD in animal models. Knockout of SerpinA3K leads to increased FoxO3 expression and improved cellular response to hypoxic injury, indicating that Serpin A3K is involved in renal oxidative response, HIF1α pathway and apoptosis[19-20].

Studies exploring the effectiveness of PHD inhibitors in renal injury have highlighted the positive effects of HIF on renal fibrosis[21]. Roxadustat (FG-4592) is a pioneering HIF-PHI developed by FibroGen nearly a decade ago. It works by inhibiting PHD proteins, thereby regulating the dynamics between HIF synthesis and degradation[22]. The drug has been approved in many countries for patients with renal anemia associated with CKD[23]. In addition, studies have shown that roxadustat affects renal injury by inhibiting inflammatory factors, reducing mitochondrial damage, and reducing the levels of Bax and cleaved caspase-3, thereby reducing apoptosis[24]. In addition, it inhibits the renal fibrosis process by maintaining redox balance and enhancing renal vascular regeneration. This effect is mediated by the HIF-1α/vascular endothelial growth factor A (VEGFA)/VEGF receptor 1 (VEGFR1) signaling pathway and the promotion of the expression of the endogenous antioxidant superoxide dismutase 2 (SOD2) [25].

Signaling pathways involved in the renal fibrosis process

Inappropriate repair after tubular injury induces progressive renal fibrosis and destruction of normal renal structure, which is considered to be a key pathological mechanism leading to CKD [26-27]. The transformation of various local stromal cells in the kidney to myoblasts plays an important role in progressive renal fibrosis, including effects on renal myoblasts and pericytes/perivascular myoblasts, EMT, endothelial cell to mesenchymal transition (EndMT) and macrophage (bone marrow-derived) to myogenic transition (MMT) [28]. Myoblasts lead to excessive production and deposition of extracellular matrix in the renal parenchyma, ultimately leading to chronic renal fibrosis and loss of renal function [29]. The complex process of renal fibrosis involves serious molecules, mainly the Wnt/β-catenin, TGFβ1/SMAD and Hippo signaling pathways.

01 Wnt/β-Catenin signaling pathway

The Wnt/α-Catenin pathway plays an important role in the occurrence and signal transduction of renal fibrosis[30-31]. Under normal circumstances, Wnt/β-catenin activation is responsible for cell repair and regeneration after acute injury of renal tissue; however, sustained activation of this pathway may lead to renal fibrosis and ultimately induce CKD[32]. In normal physiological processes, a protein complex composed of five proteins inactivates the Wnt/β-catenin pathway by phosphorylation to prevent overactivation of the pathway and renal fibrosis. However, under pathological conditions, Wnt ligands bind to Frizzled (FZD), low-density lipoprotein (LDL) receptor-related protein 5/6 (LRP5/6), and LRP, which are mainly derived from the cytoplasm of renal tubular cells, resulting in reduced phosphorylation of β-catenin and its conversion to an active form of downstream signals, including TGF-β1/SMAD signaling, RAS, Snail1, Twist1, matrix metalloproteinase 7 (MMP-7), transient receptor potential canonical 6 (TRPC6), and plasminogen activator inhibitor-1 (PAI-1), leading to fibroblast activation [33-34]. Sustained expression of Wnt ligands ultimately induces myoblast transformation, leading to fibrosis [29]. In addition, WNT/β-catenin signaling is involved in CKD-associated vascular calcification and mineral bone disease. For example, the WNT/β-catenin pathway is tightly regulated by the DKK family of proteins. In particular, DKK3 is released by "stressed" TECs, which leads to renal fibrosis and is associated with a short-term risk of CKD progression and AKI [32].

02 TGF-β1/SMAD signaling pathway

The TGF-β1/SMA signaling pathway is another important mechanism that promotes the transition to myoblasts and renal fibrosis [35]. TGF-β1 is produced in an inactive state and binds to latent associated peptide (LAP) and latent TGF-β1 binding protein (LTBP). Various triggers, such as ROS, can release TGF-β1 from LAP and LTBP, thereby activating TGF-β1. The active form of TGF-β1 binds to the type II TGF-β1 receptor (TβRII) and further binds to the type I TGF-β2 receptor (TαRI), inducing phosphorylation of the SMAD2/SMAD3 complex, thereby activating SMAD4. SMAD4 induces the translocation of SMAD2/SMAD3 from the cytoplasm to the nucleus, and this complex ultimately activates miRNA-21 and miRNA-192, ultimately leading to extracellular matrix production and renal fibrosis. In contrast, SMAD7 is an inhibitory SMAD induced by SMAD3 transcription, regulating the function of SMAD3 and acting as a negative feedback mechanism for the TGF-β1/SMAD pathway[37-38].

Under normal physiological conditions, a large amount of SMAD7 is present to inhibit the TGFβ1/SMAD pathway by degrading TβRI through the ubiquitin-proteasome degradation mechanism[39]. Under pathological conditions, overexpression of SMAD3 induces SMAD7 protein degradation by SMAD ubiquitination regulator 1 (Smurf1), SMAD ubiquitination regulator 2 (Smurf2) and arkadia[40-41]. This process further contributes to the pro-proliferative process, inducing the transition to myeloblasts and inducing the progression of renal fibrosis[42-44].

03 Hippo signaling pathway

The Hippo pathway was first discovered 20 years ago and is believed to be involved in cell growth, proliferation, and apoptosis. It plays a key role in regulating organ size, tissue regeneration, and tumor development[45]. Various physiological and pathological signals can induce the Hippo signaling pathway, including extracellular matrix (ECM) stiffness, cell polarity, and energy stress[46]. Upstream membrane receptors act as receptors for extracellular growth inhibitory signals. When inhibitory signals bind to the receptors, TAO kinase activates the Hippo pathway by phosphorylating STE20-like serine/threonine kinase 1/2 (MST1/2), forming a complex with the adapter protein Salvador 1 (SAV1). Subsequently, the complex phosphorylates large tumor suppressor (LATS1/2) and LATS1/2 interacting protein MOB kinase activator 1 (MOB1), and then the phosphorylated LATS1/2-MOB1 complex phosphorylates YAP and TAZ, which promotes cytoplasmic polyubiquitination and subsequent degradation of YAP/TAZ by the proteasome[47]. In contrast, inactivation of the Hippo pathway leads to dephosphorylation of upstream kinases, causing active YAP/TAZ to migrate to the nucleus. There, they interact with various transcription factors, including members of the TEA domain DNA binding family (TEAD1-4), to regulate cell proliferation[48]. YAP/TAZ also bind to other transcription factors, including TCF/LEF transcription factors, SMAD1, SMAD2/3, and p37[49].

Studies have shown that the Hippo pathway is associated with AKI[50]. During the AKI recovery phase, YAP protein levels in both the cytoplasm and nucleus of renal TECs are increased, and they are also positively correlated with changes in YAP and TEAD expression[51]. In addition, the Hippo pathway is associated with EMT in renal TECs, which is a key process in the transition from AKI to CKD. EMT occurs through activation of the TGF-β/Smad pathway and loss of polarity of tubular epithelial cells. This polarity is mainly maintained by the Crumbs (CRB)/PALS1 complex, which also regulates the Hippo signaling pathway[52-53]. Studies have shown that traditional Chinese medicine may affect the Hippo pathway and regulate renal fibrosis, although clinical evidence for its use in kidney disease is still insufficient [49]. Triptolide, a trioxidized diterpenoid compound, has been found to inhibit EMT in TECs and reduce renal fibrosis by regulating the Hippo signaling pathway [54]. In addition, quercetin (Triptolide), a bioflavonoid drug, activates the Hippo signaling pathway and may slow the progression of kidney disease and help prevent renal fibrosis [48]. Another compound, Verteporfn (VP), is a photosensitizer used to treat age-related macular degeneration that can bind to YAP and disrupt its interaction with TEAD, which may improve tubulointerstitial inflammation and fibrosis [55-56].

Innate and adaptive immunity

In addition to the myoblast transition, the immune system plays a crucial role in various aspects of the pathophysiology of kidney injury and repair. In the acute phase of injury, components of the innate immune system, such as macrophages and neutrophils, are recruited to the site of injury. They release proinflammatory cytokines, such as interleukin 6 (IL-6) and tumor necrosis factor-alpha (TNF-α), which enhance the inflammatory response. In the later stages of AKI, the immune system also participates in the repair process. For example, macrophages (which exhibit an M1 phenotype during acute injury and exacerbate the inflammatory process by releasing IL-1, IL-6, and TNF-α) switch to an M2 phenotype, mediating the inflammatory cascade and propagating the repair process [57-58]. However, M2 macrophages participate in renal fibrosis through MMT or a variety of growth factors [43]. TECs release Wnt ligands, which promote the phenotypic transition of macrophages from M1 to M2, thereby promoting fibrosis [59].

Macrophages also secrete Wnt proteins, TGF-β1, and TIMPs, which play a key role in renal fibrosis by participating in the synthesis and deposition of extracellular matrix [60]. Elevated complement levels in renal cells have also been implicated in the pathogenesis of renal fibrosis. For example, elevated levels of C1q in PDGFRβ-positive pericytes lead to increased inflammation and renal scarring. This has been attributed to increased production of cytokines such as IL-6, monocyte chemoattractant protein-1 (MCP-1; CCL2), and macrophage inflammatory protein-1α (MIP1-α; CCL3) [61]. C1r and C1s mRNA and protein expression also increase during fibrosis, which leads to increased levels of C3 fragments, ultimately propagating downstream responses of the complement system, leading to myofibroblast transformation and activation of renal fibrosis [62]. Animal studies have shown that C5 knockout and the use of C5R antagonists can reduce tissue fibrosis [63]. Other studies have shown that inhibition of C1r serine proteases or C3a/C3aR can effectively alleviate interstitial fibrosis in different mouse models [64-65].

The adaptive immune system is also involved in the AKI process. During the initial injury process, renal dendritic cells present antigens to T cells. Activated T cells then release proinflammatory cytokines, including interferon-γ (IFN-γ), leading to an overall inflammatory cascade [66]. Much like the phenotypic shift observed in macrophages, regulatory T cells, which are powerful mediators of the immune system, become identifiable in the kidney. These regulatory T cells inhibit the activation of many different immune cells through contact-dependent mechanisms and the release of soluble mediators such as IL-10, which induces phosphorylation of STAT1, 3, and 5, thereby promoting repair and anti-fibrotic processes after injury [67-69].

Mitochondrial dysfunction

AKI, especially ischemic injury, can lead to mitochondrial dysfunction because hypoxia disrupts the electron transport chain in mitochondria and produces excessive amounts of free radical-containing species. These harmful molecules further damage renal tubular cells[70]. In recent studies, mitochondrial dysfunction has also been increasingly recognized as a key factor in the transition from AKI to CKD[29,71]. Basically, mitochondrial homeostasis is maintained by three processes: mitochondrial dynamics, mitophagy, and mitochondrial biogenesis[72]. Mitochondrial dynamics includes two different processes: fragmentation (regulated by DRP1) and fusion (regulated by MFN1, MFN2, and OPA1). Autophagy is the process by which damaged mitochondria are selectively degraded by autophagy, which is regulated by the PINK1-PARK2 pathway, the BNIP3 and NIX pathways, and the FUNDC1 pathway. Mitochondrial biogenesis is mainly regulated by peroxisome proliferator-activated receptor γ coactivator-1α (PGC-1α), which solves the increased cellular energy demand during cell proliferation and replenishes the mitochondrial content in newly formed cells[70-73]. Animal studies have shown that regulation of these genes involved in mitochondrial homeostasis processes affects the process of kidney injury, renal fibrosis, and apoptosis of renal tubular epithelial cells[74-77]. For example, elevated levels of PGC-1α in renal tubular cells increase mitochondrial mass and provide renal protection after ischemia and acute injury without causing cell death [78]. In contrast, global loss of PGC-1α leads to severe renal dysfunction in septic AKI [77].

G2/M arrest pathway and cellular senescence

The initiation of DNA damage response (DDR) signaling is essential for the repair mechanism of proximal renal epithelial cells after AKI. When repair is incomplete, damaged cells are arrested in the G2/M phase to stabilize genetic factors [79-80]. These cells subsequently show significant upregulation of messenger RNA (mRNA) expression of profibrotic growth factors such as TGF-β1 and connective tissue growth factor (CTGF), ultimately leading to interstitial fibrosis [27-81]. Target of rapamycin (TOR) autophagy-specific coupled compartment (TASCC), a novel complex present in G2/M-arrested renal tubular cells, has been implicated in cellular senescence [82]. Cyclin G1 (CG1) plays a key role in the development of TASCC, and studies have shown that specific deletion or inhibition of CG1 in the proximal tubules, a key component of the TASCC complex, significantly attenuates renal fibrosis.

Epithelial Toll-like and IL-1 receptors (TLR/IL-1Rs) are other factors that mediate cellular senescence and G2/M arrest pathways [83]. After AKI, activation of TLRs by IL-1 and DAMPs can trigger excessive inflammatory responses and promote interstitial fibrosis; in contrast, deletion of Myd88, a TLR/IL-1 downstream protein and an NF-κB upstream protein, can improve renal fibrosis after renal injury [83-84]. Therefore, targeting tubules undergoing G2/M cell cycle arrest is a promising therapeutic approach, and several interventions have been documented. For example, piffthrin-α, an inhibitor of the key cell cycle regulator p53, is a promising candidate for use after AKI to reduce renal fibrosis after AKI [85]. The PTBA analogue methyl 4-(phenylthio)butyrate (M4PTB), a histone deacetylase inhibitor, has also been shown to reduce G2/M arrest in damaged tubular cells, thereby reducing interstitial fibrosis [86]. Other studies have revealed the effectiveness of specific inhibitors targeting cyclin-dependent kinase 4/6, a key mediator of cell cycle progression from G1 to S phase, in optimizing damaged tubular cell cycle progression [87-88].

Renin-angiotensin-aldosterone system

The RAAS is initiated by renin release from the juxtaglomerular cells of the kidney. It converts angiotensinogen formed in the liver into angiotensin I (Ag I), which is subsequently converted to angiotensin II (Ag II) through the action of angiotensin-converting enzyme (ACE). Prolonged and overactivated RAAS after AKI can lead to CKD progression through various mechanisms [89]. Binding of Ag II to Ag II receptor type 1 (AT1R) activates the RhoGEF/RhoA/ROCK cascade and induces overexpression of NF-κB, PAI-1, MAPK/extracellular signal-regulated kinase (ERK) 1/2, and NADPH oxidase. NADPH oxidase, the enzyme that generates ROS, increases intracellular oxidative stress and leads to overexpression of TGF-β/SMAD and MAPK/ERK1/2[90-91]. All of these molecules contribute to organ remodeling and tissue fibrosis. In addition, AT1R activation mediates the balance between intracellular nitric oxide (NO) and calcium levels through the PI3K/Akt pathway. Inhibition of endothelial nitric oxide synthase (eNOS) and increased cytoplasmic calcium levels through inositol 1,4,5-triphosphate (IP3) increase the resistance of the efferent arterioles and disrupt the autoregulation of the afferent arterioles, ultimately leading to glomerular hyperfiltration and sclerosis[90,992-93].

Aldosterone is a mineralocorticoid that is thought to be involved in the process of renal fibrosis, independent of its role in increasing blood pressure by mediating salt retention. Aldosterone affects the kidney by inducing the production of ROS, upregulating the expression of EGFR and AT1R, and activating NF-κB and activator protein-1 (AP-1). These molecular events further promote cell proliferation, apoptosis, and phenotypic transformation of epithelial cells, which in turn trigger the expression of TGF-β, CTGF, and PAI-1, ultimately leading to the development of renal fibrosis [94-95].

Many clinical trials support the renal protective effects of RAS inhibitors (such as ACE inhibitors and AT1a receptor blockers) in patients with diabetic or proteinuric non-diabetic CKD [96-97]. A meta-analysis involving 70,801 patients showed that exposure to ACEi/ARB after AKI was associated with a lower risk of AKI recurrence and CKD progression [98]. However, only a few observational studies have explored the effects of RAS inhibitors on the transition from AKI to CKD. Furthermore, there has not been a large-scale randomized controlled trial evaluating the effects of RAS blockade on AKI and the subsequent development of CKD. The role of RAS activity in the acute phase and severity of AKI remains uncertain.

Conclusion

The classification of renal diseases into AKI, AKD, and CKD highlights the risk of progression and the causal relationship between AKI/AKD and CKD. AKI arises after multiple insults, leading to complex pathophysiological events such as cellular hypoxia, inflammation, and nephrotoxicity, and subsequent renal injury. The inflammatory response plays a central role in AKI, and cellular stress leads to the release of DAMPs and the activation of innate immunity, resulting in further injury and fibrosis. Molecular pathways including NF-κB, MAPK, and STAT play key roles in the inflammation and fibrosis associated with AKI. Maladaptive repair mechanisms after AKI, involving the transition of various renal cells to myoblasts, have a major impact on the progression of CKD. The Wnt/β-catenin, TGF-β/SMAD, and Hippo signaling pathways play a key role in this transition, promoting fibrosis and affecting renal function. Mitochondrial dysfunction, cellular senescence, hypoxia, and RAAS are also key factors in the progression of AKI and the transition to CKD, especially RAAS, which plays an important role in renal remodeling and fibrosis. Although the importance of RAAS is recognized, more research is needed to fully understand its role in the development of AKI and subsequent CKD.

How Does Cistanche Treat Kidney Disease?

Cistanche is a traditional Chinese herbal medicine used for centuries to treat various health conditions, including kidney disease. It is derived from the dried stems of Cistanche deserticola, a plant native to the deserts of China and Mongolia. The main active components of cistanche are phenylethanoid glycosides, echinacoside, and acteoside, which have been found to have beneficial effects on kidney health.

Kidney disease, also known as renal disease, refers to a condition in which the kidneys are not functioning properly. This can result in a buildup of waste products and toxins in the body, leading to various symptoms and complications. Cistanche may help treat kidney disease ase through several mechanisms.

Firstly, cistanche has been found to have diuretic properties, meaning it can increase urine production and help eliminate waste products from the body. This can help relieve the burden on the kidneys and prevent the buildup of toxins. By promoting diuresis, cistanche may also help Reduce high blood pressure, a common complication of kidney disease.

Moreover, cistanche has been shown to have antioxidant effects. Oxidative stress, caused by an imbalance between the production of free radicals and the body's antioxidant defenses, plays a key role in the progression of kidney disease. ies help neutralize free radicals and reduce Oxidative stress, thereby protecting the kidneys from damage. The phenylethanoid glycosides found in cistanche have been particularly effective in scavenging free radicals and inhibiting lipid peroxidation.

Additionally, cistanche has been found to have anti-inflammatory effects. Inflammation is another key factor in the development and progression of kidney disease. Cistanche's anti-inflammatory properties help reduce the production of pro-inflammatory cytokines and inhibit the activation of inflammation mandatory pathways, thus alleviating inflammation in the kidneys.

Furthermore, cistanche has been shown to have immunomodulatory effects. In kidney disease, the immune system can be dysregulated, leading to excessive inflammation and tissue damage. Cistanche helps regulate the immune response by modulating the production and activity of immune cells, such as T cells and macrophages. This immune regulation helps reduce inflammation and prevent further damage to the kidneys.

Moreover, cistanche has been found to improve renal function by promoting the regeneration of renal tubes with cells. Renal tubular epithelial cells play a crucial role in the filtration and reabsorption of waste products and electrolytes. In kidney disease, these cells can be damaged, leading to damaged renal function. Cistanche's ability to promote the regeneration of these cells helps restore proper renal function and improve overall kidney health.

In addition to these direct effects on the kidneys, cistanche has been found to have beneficial effects on other organs and systems in the body. This holistic approach to health is particularly important in kidney disease, as the condition often affects multiple organs and systems. che has been shown to have protective effects on the liver, heart, and blood vessels, which are commonly affected by kidney disease. By promoting the health of these organs, cistanche helps improve overall kidney function and prevent further complications.

In conclusion, cistanche is a traditional Chinese herbal medicine used for centuries to treat kidney disease. Its active components have diuretic, antioxidant, anti-inflammatory, immunomodulatory, and regenerative effects, which help improve renal function and protect the kidneys from further damage. , cistanche has beneficial effects on other organs and systems, making it a holistic approach to treating kidney disease.