Review Article

Renal Amyloidosis: Complications and Management in the Hospital Setting

Kinjal Shah¹, Soura Rajeshwara², Christina Thymalil³, Alberto Ayala Aguilar^4,5, Erick Ayala Aguilar⁴, Ghazala Anjum⁶, Linette Pakroo⁷, Rishita Dave⁸, Ileana Patricia Crespin Henriquez⁹, Vianka Vanessa Yanez Montalvo¹⁰, Melanie Dayana Yanez Montalvo¹⁰, Maria Isabel Gomez-Coral^11*

¹Rutgers Edwards J Bloustein School of Public Policy and Planning, NJ, USA

²Shimoga Institute of Medical Sciences, Shivamogga, India

³Nova Southeastern University Dr. Kiran C. Patel College of Osteopathic Medicine (NSU-KPCOM)

⁴Universidad del Noreste, México

⁵University of Texas, MD Anderson Cancer Center, USA

⁶Liaquat College of Medicine & Dentistry, Karachi, Pakistan

⁷Windsor University, St. Kitts

⁸University of Medicine and Health Sciences, Saint Kitts

⁹Universidad Evangélica de El Salvador, El Salvador

¹⁰Universidad de Guayaquil, Ecuador

¹¹Universidad del Valle, México

Submission: November 07, 2024;;Published: November 18, 2024

*Corresponding author: Maria Isabel Gomez Coral, Department of Medicine, Universidad del Valle de, Mexico

How to cite this article: Kinjal S, Soura R, Christina T, Alberto Ayala A, Erick Ayala A, et al. Renal Amyloidosis: Complications and Management in the 002 Hospital Setting. JOJ Urology & Nephrology, 2024; 9(2): 555757. DOI:10.19080/JOJUN.2024.09.555757.

Abstract

Renal amyloidosis is a complex and progressive disease that leads to significant morbidity, particularly in the hospital setting, where complications can rapidly worsen patient outcomes. This article reviews the complications and management strategies associated with renal amyloidosis in hospitalized patients, focusing on the challenges posed by nephrotic syndrome, increased infection risk, and multi-organ involvement. Diagnostic obstacles in identifying renal amyloidosis in acutely ill patients are explored, emphasizing the need for a high index of suspicion and a comprehensive diagnostic approach. Management strategies highlighted include supportive care, infection prevention, fluid and electrolyte management, and targeted treatments for the underlying amyloid disease. Effective care requires a multidisciplinary team approach, bringing together expertise from nephrology, cardiology, infectious disease, and nutrition to address the diverse needs of these patients. By integrating early diagnosis with a collaborative care model, healthcare teams can improve the prognosis and quality of life for patients facing this challenging condition.

Keywords: Renal Amyloidosis; Nephrotic Syndrome; Multidisciplinary Care

Abbreviations: GIT: Gastrointestinal tract; NIDDK: National Institute of Diabetes and Digestive and Kidney Diseases; ESRD: End-stage renal disease; AL: Light Chain (amyloidosis); AA: Serum Amyloid A (amyloidosis); SAA: Serum Amyloid A; ATTR: Transthyretin (amyloidosis); TTR – Transthyretin; ApoAI: Apolipoprotein AI: ApoAII: Apolipoprotein AII; ApoAIV: Apolipoprotein AIV; SSA: Senile systemic amyloidosis; NT-proBNP: N-terminal pro B-type natriuretic peptide; CT : Computed Tomography; GI: Gastrointestinal; GI tract: Gastrointestinal tract; CKD: chronic kidney disease; AKI - Acute Kidney Injury; RTA: Renal Tubular Acidosis; AL: Light Chain (amyloidosis); PET-CT - Positron Emission Tomography: Computed Tomography: MRI - Magnetic Resonance Imaging; Echocardiography - Echocardiogram (commonly referred to as Echo): Congo red: A staining method (not abbreviated, but mentioned); PET: Positron Emission Tomography: RNAi - RNA interference; FDA: Food and Drug Administration; TTR: Transthyretin; CRISPR: Cas9 - Clustered Regularly Interspaced Short Palindromic Repeats: CRISPR-associated protein 9; sFLC – Serum: free light chains; eGFR: Estimated Glomerular Filtration Rate; NT-proBNP: N-terminal pro B-type natriuretic peptide; TTR: Transthyretin; CT: Computed Tomography; PET: Positron Emission Tomography

Introduction

Amyloidosis is a group of disorders characterized by abnormal protein (known as amyloid) buildup in tissues and organs, causing progressive damage, which may lead to death [1,2]. Amyloidosis may occur in organs such as the kidneys, heart, liver, spleen, nervous system, GIT, glands, musculoskeletal system, eyes, and oral cavity [3,4]. Amyloidosis can affect more than one organ at the same time; the symptoms and severity of the disease depend upon the affected organs and tissues. The kidney and heart are the most commonly affected [4]. Currently, 37 different proteins have been discovered to form amyloid deposits in tissue. Of these, 33 are secreted outside the cell (extracellular), and 4 are secreted inside the cell (intracellular) [5]. In the kidneys, amyloid buildup can affect glomerular filtration, leading to proteinuria, kidney damage, and renal failure [6,7]. According to the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK), nephrotic syndrome is the most common sequelae of amyloid deposition in the kidneys [7].

Untreated renal amyloidosis will ultimately lead to end-stage renal disease (ESRD) or death in a majority of cases [8]. Complications of ESRD include uremia, hyperkalemia, volume overload, heart disease, high blood pressure, and anemia [9-11]. Unfortunately, there is currently no cure for amyloidosis [12]. Ultimately, managing this illness aims to reduce amyloid burden and maintain or improve renal function by preventing further kidney injury (measurable by renal function tests). This is managed by therapy targeting the underlying amyloid formation process and supportive management [8]. The efficacy of the amyloidosis treatment depends on the specific proteins involved. Hence, management and prognosis are complicated due to the amyloid proteins' heterogeneous composition [13].

Treatment of renal amyloidosis may be hindered owing to its delay in diagnosis, as its initial symptoms (such as proteinuria and renal insufficiency) are non-specific. This may lead to the development of significant renal damage before the illness is finally diagnosed. Furthermore, diagnostic techniques often used have low sensitivity and specificity and may fail to distinguish between amyloid protein types, which leads to less specific treatment [13].

Pathophysiology

The mechanisms of amyloid deposition vary significantly among different types of amyloidosis. In AL (Light Chain) amyloidosis, the pathogenesis begins with plasma cell dyscrasia, leading to the overproduction of monoclonal light chains, predominantly λ chains. These abnormal light chains undergo conformational changes, forming β-sheet structures that aggregate into oligomers and eventually mature fibrils. The specific sequence variations in light chains influence their tissue tropism, commonly affecting the heart, kidneys, liver, and peripheral nerves. On the other hand, AA (Serum Amyloid A) amyloidosis develops secondary to chronic inflammatory conditions where persistent elevation of SAA protein occurs. The SAA protein undergoes proteolytic cleavage, and its N-terminal fragments form fibrils that predominantly deposit in the kidneys, spleen, liver, and GI tract [14,17]. Hereditary amyloidosis encompasses several distinct types, with ATTR (Transthyretin) being the most common. In ATTR, mutations in the TTR gene lead to destabilization of the TTR tetramer, resulting in monomer misfolding and rapid fibril formation. These deposits typically affect the heart and peripheral nerves and can cause carpal tunnel syndrome. Other hereditary forms include fibrinogen amyloidosis, where mutations in the fibrinogen α chain lead to predominantly renal deposition, and various apolipoprotein amyloidoses (ApoAI, ApoAII, ApoAIV), each with specific organ tropism.

Despite their different origins, all types share standard features in fibril formation, including protein misfolding, β-sheet structure formation, oligomerization, and mature fibril assembly. The resulting tissue damage occurs through direct cellular toxicity, mechanical disruption, oxidative stress, and inflammation. The progression of each type is influenced by factors such as protein concentration, environmental conditions, genetic modifiers, and age-related changes, leading to distinct patterns of organ involvement and clinical manifestations [14-16]. The type of amyloidosis can also determine clinical manifestation as specific groups of amyloidosis are associated with deposition in specific organ systems, such as wild-type transthyretin (ATTR) amyloidosis, which predominates in the cardiovascular system [17]. Wild-type ATTR cardiac amyloidosis presents as a restrictive cardiomyopathy due to excessive accumulation of misfolded protein. Clinicians will see increased bi-ventricular wall thickness and stiffness; atrial infiltration of wild-type ATTR can manifest as atrial fibrillation.

Wild-type ATTR amyloidosis is also associated with bilateral carpal tunnel, spinal stenosis, and biceps tendon rupture [18]. Non-hereditary transthyretin amyloidosis is also called senile systemic amyloidosis (SSA) due to its prevalence in older populations. Hereditary transthyretin amyloidosis, on the other hand, is an autosomal dominant mutation in Chromosome 18 with an early onset in patients around the 3rd decade [19]. In addition, AL amyloidosis, which most commonly involves the multi-organ system, also has important implications for the cardiovascular system.

In AL amyloidosis, amyloid proteins can deposit in arterioles in the heart, resulting in angina and even myocardial infarction. Free light chains seen in AL amyloidosis encourage lysosomal dysfunction, inducing the production of reactive oxygen species and cardiomyocyte death [18]. Definitive diagnosis is made through Congo red staining of cardiac biopsy; other serum biomarkers such as NT-proBNP and troponin may also be elevated [19]. Mainstay medical therapies are loop diuretics and mineralocorticoid receptor antagonists. Because of joint autonomic nervous system involvement, vasoconstrictors such as midodrine may be used to treat orthostatic hypotension [18].

Amyloidosis involving the respiratory system is rare, but uncommonly, amyloid protein can deposit in the pulmonary parenchyma and submucosa of bronchi and trachea, hilum of the lungs and lymph nodes, and pleura of the mediastinum where it clinically manifests as dyspnea, chest tightness, cough and hemoptysis [20]. Tracheobronchial amyloidosis was the most seen subtype of respiratory amyloidosis, with the less common presentation of nodular amyloidosis, infiltrating interstitial amyloidosis, and lymph node amyloidosis. Imaging tracheobronchial amyloidosis demonstrated non-specific findings such as increased lung markings, atelectasis, obstructive pneumonia, stenosis of the trachea, and thickened trachea and bronchus [20]. Bronchoscopy likely showed protrusions, thickening, and stenosis of the bronchial wall [20]. Management of respiratory amyloidosis is mainly dependent on symptomatology and presentation.

Gastrointestinal involvement can be seen in systemic and localized amyloidosis, characterized by the accumulation of extracellular misfolded protein in the different layers of the GI tract [21]. Infiltration of the mucosal layers is most seen in the duodenum, followed by the stomach. AL amyloidosis has been documented to infiltrate the muscularis mucosa, submucosa, and muscularis propria, leading to the formation of protrusion, which clinically manifests as bowel obstruction [21].

However, AA amyloidosis presents as diarrhea and malabsorption due to preferred involvement in the mucosa, leading to mucosal friability and inflammation erosion. Amyloidosis of the intrinsic nerve plexus and muscularis externa, which includes myenteric nerve plexus, submucosal nerve plexus, and the longitudinal and circular muscles in the GI system, leads to abnormal peristalsis, gastric emptying, and dysmotility [21]. GI involvement of amyloidosis may present with non-specific symptoms such as weight loss, fatigue, and anemia due to GI bleed; thus, ruling out other causes is vital.

Furthermore, hepatic amyloidosis presents as infiltration deposition of misfolded amyloid protein in the liver parenchyma, along sinusoids, and within blood vessel walls, causing excessive compression of hepatocytes [22]. In advanced cases, hepatomegaly and "rubbery elastic" consistency of the surface of the liver are seen; hepatic rupture, portal hypertension, and hepatic failure are rarely seen; however, they can occur; thus, a liver biopsy must be done with caution as not to trigger spontaneous rupture and hemorrhage. Other manifestations of hepatic involvement include proteinuria, elevated serum alkaline phosphatase, hyposplenism as characterized by Howell-Jolly bodies on peripheral blood smear, and hepatomegaly inconsistent with liver enzyme values. Radiological findings could be more specific. CT scans have been known to show hepatomegaly with heterogeneous decreased attenuation and rare calcifications [22]. Proteinuria and disease progression in renal amyloidosis are intimately connected through several mechanisms. Initially, amyloid deposits in the glomerular basement membrane and mesangium disrupt the normal filtration barrier, leading to protein leakage. This process begins with the loss of the glomerular filter's charge selectivity and size selectivity, primarily due to podocyte injury and effacement of foot processes caused by amyloid deposits. Proteins, mainly albumin, leak into the tubular system, triggering damaging effects. These filtered proteins are toxic to tubular cells, leading to tubular inflammation and fibrosis. The increased protein reabsorption by proximal tubular cells triggers the release of pro-inflammatory cytokines and growth factors, further promoting interstitial inflammation and fibrosis [14-22]. This creates a vicious cycle where proteinuria becomes a disease progression driver. The persistent high-grade proteinuria leads to hypoalbuminemia, which can worsen tissue edema and potentially increase amyloid deposition due to altered protein homeostasis. Additionally, the loss of specific binding proteins in the urine can lead to various metabolic complications. The severity of proteinuria often correlates with the rate of decline in renal function - patients with higher levels of proteinuria typically experience faster progression to nephrotic syndrome, leading to end-stage renal disease. Moreover, heavy proteinuria contributes to cardiovascular complications through multiple mechanisms, including altered lipid metabolism and increased thrombotic risk, which can further complicate the disease course [14-22].

Clinical Manifestations in Hospitalized Patients

Nephrotic Syndrome

A frequent renal complication in renal amyloidosis is nephrotic syndrome, a clinical scenario in which heavy proteinuria, hypoalbuminemia, and hypercholesterolemia are seen. Studies have shown that nearly 75% of the patients with renal amyloidosis present with peripheral edema secondary to nephrotic syndrome, renal failure, heart failure, or a mixture of these pathologies. Renal amyloidosis will present proteinuria from subnephrotic ranges to massive proteinuria with ranges from 20 to 30g/d, with over 65% of the patients developing nephrotic syndrome. Previous clinical retrospective data obtained from a revision of 474 found that peripheral edema could be present in up to 78% of the cases of renal amyloidosis [23-24].

Renal Amyloidosis: Chronic Kidney Disease (CKD) and Acute Kidney Injury (AKI)

The underlying mechanism behind the disruption of renal tissue is the deposition of amyloid in the renal cell architecture. This mechanism will eventually lead to latent tissue deposition of amyloid, progressing from a symptomatic stage to a proteinuric state lasting 10 to 20 years, followed by nephrotic and uremic phases, ultimately reaching end-stage renal disease within the same timeframe [25]. The chronic deposition of amyloid in the kidney is associated with progressive deterioration of renal function. The two described mechanisms are as follows: The first mechanism involves the accumulation of amyloid fibrils in the extracellular space, causing disruption and malfunction of surrounding tissue. The second mechanism considered an alternative is direct cellular toxicity caused by amyloidogenic precursor proteins, folding intermediates, aggregates, or fibrils. This latter mechanism may be mediated through interactions with cell surface receptors or entry into cells [24]. Acute kidney injury could be present in rare cases secondary to tubular cast amyloid nephropathy. Other Intrarenal complications are seen in renal amyloidosis; for example, Renal Tubular Acidosis (Type 1 RTA) or polyuria due to nephrogenic diabetes insipidus may be present in patients with severe tubular damage from amyloid deposition [26].

Extra-Renal Manifestations

In patients with renal amyloidosis, systemic amyloidosis can lead to extrarenal complications that exacerbate renal disease and impact overall prognosis. These manifestations often involve multiple organ systems, with particularly significant effects on the cardiovascular, autonomic, and gastrointestinal systems. Recognizing these complications in hospitalized patients is crucial for effective management and for preventing further deterioration of renal function [27-34].

Cardiovascular Complications

Cardiac involvement is common in systemic amyloidosis and can severely impact renal outcomes. Amyloid deposits in the myocardium can lead to restrictive cardiomyopathy, a condition characterized by impaired ventricular filling, leading to diastolic dysfunction and, ultimately, heart failure. This type of heart failure can be resistant to conventional therapies, and the presence of volume overload can worsen renal function, particularly in hospitalized patients. Additionally, amyloid deposition in the cardiac conduction system can lead to arrhythmias, which may require monitoring and management to prevent further complications [27-29].

Autonomic Dysfunction

Autonomic neuropathy is another significant extrarenal manifestation of systemic amyloidosis that complicates renal disease management. Patients may experience orthostatic hypotension, which can be severe and lead to falls or syncope, particularly in the hospital setting where mobility is often reduced. This condition complicates fluid management in patients with renal amyloidosis, as the balance between hypotension and volume overload becomes challenging to maintain. Autonomic dysfunction can also affect gastrointestinal motility and bladder function, further complicating care [30,31,34].

Gastrointestinal Manifestations

Gastrointestinal involvement in amyloidosis can be presented as malabsorption, chronic diarrhea, or constipation due to amyloid infiltration of the gastrointestinal tract. These symptoms can exacerbate malnutrition, which is already a concern in patients with renal disease, and lead to poor wound healing, delayed recovery, and increased susceptibility to infections. Additionally, gastrointestinal bleeding, although less common, can occur and may be difficult to control due to amyloid-related vascular fragility. Effective nutritional support and vigilant monitoring for gastrointestinal bleeding are essential in managing these patients in the hospital [32,33].

Diagnostic Challenges in the Hospital Setting

Diagnosing renal amyloidosis in hospitalized patients presents significant challenges due to its nonspecific symptoms, variable organ involvement, and overlap with other chronic conditions. Misdiagnosis or delayed diagnosis can lead to inappropriate treatment and worsen patient outcomes. Early and accurate diagnosis requires high clinical suspicion and appropriate use of laboratory and imaging modalities.

Nonspecific Clinical Presentation

Renal amyloidosis often presents with generalized symptoms such as fatigue, weight loss, and edema, which are common in various chronic and acute illnesses seen in hospitalized patients. These nonspecific symptoms make it challenging to identify renal amyloidosis without targeted testing. Patients frequently present with proteinuria or nephrotic syndrome, but these findings may also be seen in other kidney diseases, such as diabetic nephropathy or membranous nephropathy. Therefore, renal biopsy remains essential for definitive diagnosis, yet it is often delayed due to overlapping clinical features that mask the underlying cause [35].

Renal biopsy with Congo red staining and light microscopy is the gold standard for diagnosing renal amyloidosis, as it can confirm amyloid deposits and allow subtyping. However, in the hospital setting, obtaining a renal biopsy may be challenging due to patients’ comorbidities, anticoagulation therapy, and risk of bleeding. The biopsy also requires high histological expertise, and misinterpreting amyloid subtypes can lead to inadequate treatment [35-38]. In cases where biopsy is contraindicated, less invasive techniques, such as abdominal fat pad aspiration, can be used, but these have lower sensitivity and specificity in systemic amyloidosis, especially for renal involvement [38].

Limitation Biomarkers

Serum and urine markers, such as monoclonal protein studies and free light chain assays, can aid in diagnosing renal amyloidosis, particularly in AL (light chain) amyloidosis. However, these tests may yield false negatives or be non-specific, especially in patients with chronic kidney disease (CKD) or multiple comorbidities. False negatives are more likely in hospitalized patients with rapidly progressing renal dysfunction or high levels of background proteinuria. This diagnostic uncertainty often delays diagnosis and treatment initiation, worsening renal function [38-41].

. Imaging Modalities

Although non-invasive imaging tools like echocardiography and MRI can suggest cardiac amyloidosis, specific imaging for renal amyloidosis remains limited. PET-CT or MRI can sometimes indicate systemic amyloidosis by identifying soft tissue or organ infiltration. Still, these are often less specific in the kidneys and may not show definitive amyloid involvement. Thus, imaging is typically used with biopsy results rather than as a standalone diagnostic modality [35,39,41].

Complications of Renal Amyloidosis in Hospitalized Patients - References

Patients with renal amyloidosis who are present with nephrotic syndrome face a heightened risk of complications, particularly infectious ones, due to immune system suppression linked to hypoalbuminemia and protein loss. Nephrotic syndrome is associated with the urinary loss of critical proteins, including immunoglobulins, which play a vital role in immune response. The resultant hypoalbuminemia not only reflects this loss but also exacerbates immune impairment, rendering patients more vulnerable to bacterial infections and opportunistic pathogenicity to infection, significantly impacting patient outcomes in the hospital setting. For instance, studies have shown that hospitalized patients with renal amyloidosis and nephrotic syndrome experience higher rates of severe infections, which can prolong hospital stays and complicate treatment regimens. These infections often require aggressive management, as their progression can lead to systemic complications that may further destabilize kidney function. Therefore, closing for early signs of infection, combined with the judicious use of prophylactic antibiotics, is recommended to mitigate these risks and improve patient prognosis in a hospital environment [42-45].

Management Strategies for Hospitalized Patients

Managing hospitalized patients with renal amyloidosis requires a focus on supportive care, infection prevention, and treatment for underlying amyloidosis. Supportive care, including careful fluid and electrolyte management, is crucial, particularly for patients with nephrotic syndrome or concurrent cardiac involvement. Diuretics may be used to reduce edema, but fluid and sodium intake should be carefully restricted to prevent volume overload and worsening renal function from protein loss and hypoalbuminemia in nephrotic syndrome. Patients with renal amyloidosis face a high risk of infections, which can worsen hospital outcomes. Prophylactic antibiotics and vaccinations against pneumococcus and influenza may benefit these patients [46-51].

Additionally, early signs of infection must be vigilantly monitored to allow prompt intervention and minimize complications. The underlying amyloidosis should be considered and tailored to the amyloid subtype. AL amyloidosis patients, for example, may benefit from plasma cell-directed therapies to reduce amyloidogenic light chains, while those with AA amyloidosis require management of the underlying inflammatory condition. A multidisciplinary team involving nephrology, infectious disease, and cardiology specialists can optimize care and support better long-term outcomes [46-51].

Multidisciplinary Care and Collaboration

Multidisciplinary care is essential in managing renal amyloidosis, as these patients often present with multi-organ involvement requiring coordinated expertise across various specialties. Nephrologists are central in managing renal complications, including nephrotic syndrome and fluid balance. At the same time, cardiologists are essential for assessing and managing potential cardiac amyloid infiltration, which can complicate renal function and overall prognosis. The collaboration between these specialists allows for more comprehensive care tailored to the complex needs of these patients [52,53].

Infection prevention and management are critical components of care in renal amyloidosis, given the immunosuppressive effects of nephrotic syndrome and hypoalbuminemia. Infectious disease specialists contribute by advising on prophylactic antibiotics, vaccination strategies, and timely identification and management of infections, which are frequent and severe in amyloidosis patients. Additionally, dietitians play a vital role in managing nutritional needs, especially with the protein losses seen in nephrotic syndrome, aiming to improve nutritional status without exacerbating edema or worsening renal function [52-54].

Regular multidisciplinary team meetings allow for ongoing evaluation of the patient’s status and adjustments to the treatment plan as necessary. This collaborative approach has been shown to improve patient outcomes by enabling prompt identification of complications and individualized treatment adjustments. As a result, integrating a multidisciplinary team in the hospital setting for renal amyloidosis patients ensures that the various systemic complications are managed cohesively, leading to a more favorable prognosis and better quality of life for patients [52-55].

Emerging Research and Future Directions

Hereditary amyloidosis is a complex genetic condition characterized by accumulating amyloid proteins in various tissues, leading to progressive organ damage [56]. It has recently become a focal point for innovative therapeutic research. Targeted therapies, RNA interference (RNAi) agents, and gene-editing techniques are being explored as potential solutions for managing and possibly curing these debilitating conditions. Targeted therapies are a promising avenue due to their potential to precisely interrupt disease pathways at the molecular level with specific proteins involved in the disease process [57]. Many ongoing studies are investigating small-molecule inhibitors and monoclonal antibodies that bind directly to amyloid fibrils, aiming to disrupt or prevent their formation [57,58]. These therapies are designed to reduce amyloid deposition in organs, thereby slowing the progression of organ damage, alleviating disease symptoms and improving patient outcomes [57,58]. By tailoring treatment to target specific amyloid types, researchers hope to limit off-target effects and achieve more favorable therapeutic outcomes.

Novel Therapies

RNA interference (RNAi) agents, such as patisiran, represent a novel class of therapies that silence genes responsible for amyloid precursor proteins [59]. Patisiran is an FDA-approved RNAi agent that targets transthyretin (TTR) mRNA explicitly, reducing the production of the amyloidogenic TTR protein implicated in hereditary transthyretin amyloidosis [60]. This mechanism helps slow or halt disease progression, offering symptomatic relief for affected individuals [60]. Ongoing clinical trials are assessing the efficacy and safety of other RNAi agents and exploring optimal dosing schedules to maximize benefits while minimizing potential side effects.

Gene-editing techniques, particularly those leveraging CRISPR-Cas9 technology, are being explored for their curative potential in hereditary amyloidosis. By directly targeting and modifying the DNA of affected genes, CRISPR-based approaches aim to prevent the production of amyloidogenic proteins altogether [60,61]. This method, still in the experimental stages for amyloidosis, could eventually allow for single-treatment cures by permanently correcting disease-causing mutations [61]. While promising, gene-editing techniques' long-term effects and safety require careful study before they become widely available.

Biomarkers and Personalized Medicine

In renal amyloidosis, biomarkers hold significant potential to improve diagnosis, guide treatment, and monitor disease progression, particularly in light-chain (AL) amyloidosis, the most common form affecting the kidneys. Amyloid fibrils damage kidney tissues and make early detection crucial, as symptoms often appear late, leading to delayed diagnosis [53,54,60]. Key biomarkers, such as serum-free light chains (sFLC) and proteinuria, help identify AL amyloidosis by indicating the presence and progression of amyloid deposits [61]. Elevated serum creatinine and reduced estimated glomerular filtration rate (eGFR) are used to assess kidney function. However, they lack specificity to amyloidosis alone and do not fully capture the disease's complexity [53].

Emerging biomarkers, like galectin-3, have shown promise in predicting kidney injury and overall mortality in renal diseases, although further studies are needed to confirm their prognostic value, specifically for amyloidosis patients [62]. Cardiac biomarkers, including troponin and N-terminal pro-B-type natriuretic peptide (NT-proBNP), are also used in AL amyloidosis to evaluate cardiac involvement, which impacts patient outcomes [63-65]. Although traditionally focused on cardiac staging, these biomarkers could enhance renal staging if adapted to better reflect renal-specific progression [66]. Research is ongoing to develop a unified biomarker model for renal amyloidosis, although current limitations exist due to the disease's variability and the need for better-targeted renal-specific markers. Novel imaging techniques and biomarkers may further improve early diagnosis and tailored treatments. At the same time, anti-amyloid therapies, still under study, offer a future avenue to reduce amyloid deposits and potentially reverse some organ damage.

Conclusion

Renal amyloidosis presents a unique set of complications that make hospitalization particularly challenging, necessitating prompt recognition, comprehensive management, and interdisciplinary collaboration. Complications such as nephrotic syndrome, immunosuppression, and multi-organ involvement contribute to heightened morbidity and necessitate a multifaceted treatment approach to prevent rapid deterioration. Effective management in the hospital setting hinges on integrating supportive care, infection prevention, and targeted therapy for the underlying amyloid disease. Additionally, a multidisciplinary team approach ensures that each aspect of the disease is managed cohesively, offering the best chance for stabilization and improved patient outcomes. As research advances, new therapies and protocols hold promise for refining care strategies, ultimately aiming to improve the long-term prognosis of patients with renal amyloidosis in the hospital setting.

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