Nephrogenic Systemic Fibrosis (NSF) Best Nephrologist In Delhi | Dr Rajesh Goel | Kidney Care Centre

Introduction

• Though an infrequent occurrence, NSF mostly affects people with a renal-related ailment, which is a severe and progressive fibrosing illness.
• Since their introduction in 1997, GBCAs have been linked to NSF in MRI Of the several GBCAs available, namely, gadopentetate dimeglumine, gadoterate meglumine, gadoversetamide, and gadobutrol, it is preferred for enhance MRI widespread application in diagnosing diseases. 
• This organization was unveiled early in the new millennium when it emerged that many patients with severe renal insufficiency, after taking GBCAs had been identified. 
• To enhance the images collected through MRI, contrast agents have the heavy metal called gadolinium.

Prevalence and Incidence

• The most observed GBCA related disease, incidence in patients with severe renal impairment is less than 4%. With the recommendations of the subsequent guidelines that restricted the utilization of GBCAs in at-risk patients, the occurrence significantly fell

Clinical Impact

• The strange casting of the skin and tissues in NSF patients is because of excessive development of fibrous tissue consequently after stimulation of these fibroblasts. 
• The clinical implication of NSF is that the skin, which is the primary affected organ becomes thickened, rough, and woody in nature. Fibrosis commonly starts in the lower extremities and then spreads to right across the axis of the body to the upper extremities. 
• Patients with severe joint contractures confining movements and causing severe pain. 
• The effects may also be life-threatening for those with conditions that affect internal organs such as the Kidneys along with other organs like heart, lungs and the liver, apart from the skin.

Causes

• Gadolinium is usually cleared rapidly by the kidneys but in patients with renal failure; it remains in patients’ body for longer duration which may be unsafe and produces fibrotic reactions.
•  Hence the cause of NSF remains undetermined, however, it is believed that gadolinium deposited in the tissues launches a fibrotic process. 
• Patients experiencing kidney diseases are especially affected because they have a shorter elimination half-life of gadolinium and, thus, can only eliminate the said compound from their bodies minimally.
• But they do not know how NSF pathophysiology works and that is essentially complex. Still, the ability of gadolinium ions to desquamate from chelates and to concentrate in various tissues, is present.
•  Thus, it is assumed that the deposition activates fibroblasts – the cells that are responsible for creation of collagen and other elements of the extracellular matrix. 

Risk Factors 

• The main risk factor for NSF in patients with severe renal impairment is exposure to GBCAs. Other factors include Acute renal damage, chronic kidney disease, and the number and length of exposures to GBCAs. 
• The other significant risk factors are the type or kind of employed gadolinium chelate (non-ionic linear agents have a higher risk) and the administration of higher quantities of GBCAs. 
• Due to protective measures placed on its usage especially in patients with impaired kidney function, NSF which is a very rare disease has been reported to be increasingly irritate rare.
•  The main population that are mostly affected by the disorder are those undergoing dialysis and those with end stage renal disease (ESRD).

Other contributing factors include as mentioned above are 

• Renal dysfunction patients
• with chronic kidney disease (CKD) are most affected and the highest risk is those in stage 4 and 5. The renal clearance of gadolinium in these phases is reduced due to remarkable decline in the GFR conspicuous in these phases. 
• Acute Kidney Injury (AKI): Patients having contrast-enhanced imaging during or shortly after AKI experience are prone to NSF because acute kidney injury will slow down the clearance of gadolinium.
• Patients on Hemodialysis or Peritoneal Dialysis are at risk since their kidneys’ ability to excrete gadolinium is reduced. Dialysis will remove a large part of the Gadolinium; however, it isn’t a 100% technique and may remain at the danger of NSF from remaining Gadolinium. 
• Prolonged Gadolinium Retention Impairs Renal Clearance: Filtration and excretion of gadolinium by kidneys are influenced with renal ailing especially when the kidneys are not functioning properly. This results in the body retaining gadolinium for a long time which can accumulate in various tissues and causes fibrosis. 
• The Inflammatory Reaction Fibroblast Activation: Gadolinium ions possess the capability of getting lodged in tissues and promoting inflammation if they are released from chelates. Myofibroblasts, fibroblasts and collagen as well as other Extra Cellular Matrix components are stimulated to form in response to this stimulus. 
• Fibrosis: The overproduction of collagen and fibrosis caused by these cells’ activation leads to the thickening and the increase of hardness of the skin as well as other tissues characteristic of NSF.

Signs and symptoms

• NSF impacts other body systems such as renal system, skin, musculoskeletal system as well as harming interior body organs. Here is a thorough rundown of all the symptoms, including kidney-related ones: 
• Renal Impairment: Those patients with non-specific fevers, most of them have severe renal failure. 
• Oliguria or low output and anuria or no output at all may operational perhaps be due to impaired functionality of the kidneys.
• This may build up more fluid in the lungs (pulmonary edema), as well as make one develop difficulty in breathing as well as swelling around the legs, ankles and feet (edema). 
• Consequently, due to often high arterial pressure, chronic renal disease is further complicated by the development of NSF. 
• In a state of hyperkalemia, the changes concerning the resting membrane potential put considerable strain on the heart as they jeopardize the normal generation of a population of action potential by cardiac pacemaker cells thus worsening and lead to cardiac arrhythmias.
• Dialysis Complications: The patient under dialysis feels the following complications like the complications of the station of access, clotting or infections.

• Once NSF has affected the skin, they could get dark hence have a hyperpigmentation According to NSF they may change color and become dark.
• It becomes pale and delicate; shrinking can be primary from fingers and toes and secondary from the arms and thighs and the trunk.
• “Peau d’orange” appearance: It may also cause skin rashes on the skin that changes it outlook to resemble an orange skin. 
• They may heal easily leaving a depression or become in elevated patches or lumps, all the of which give skin an increased thickness. 
• Musculoskeletal Joint Stiffness and Pain: Again, some of the depressing signs of arthritis are pain and stiffness of the joints and therefore, movement is restricted. 
• Pertaining to grave skin alteration, there are good grounds to believe that tight or intense fibrosis accustomed to ichthyosis, sometime skin cracking, stunted growth, immovable joints, and retarded physique developments.
• Reduced Mobility: Both, and contracture, are associated with joint pain and progression of stiffness reducing mobility and ADL. 
• Other cardiac issues include restrictive cardiomyopathy, and such can manifest itself in a situation where fibrosis has developed in the heart. 
• Lungs: Therefore, the patients will experience pulmonary fibrosis followed by diaphragmatic fibrosis and respiratory disorder, restricting lung disease. 
• Gastrointestinal system: All the symptoms related to swallowing and other GI aspects are traced to esophagitis and other Primary Organs of the Digestive System.

Other Symptoms include 

• Pruritus (Itching)
• Muscle Weakness
• Burning Sensations

Diagnosis

Clinical Assessment:

• To start off, the doctor will need to get a complete medical history from patients. They’ll pay special attention to any recent exposure you might have had to gadolinium-based contrast agents, as well as your renal (kidney) health and whether patients have undergone dialysis treatment.

Symptoms:

• Next, the doctor will be on the lookout for the typical signs and symptoms of NSF. These can include skin alterations, joint problems, and possible systemic involvement. It’s important to recognize these symptoms early on.

Physical Inspection:

• During the physical examination, the doctor will check for specific things:

• Skin Modifications:
• They’ll carefully examine the patient skin, looking for any changes. They’ll take note of any skin that feels thicker, harder, and has a “peau d’orange” texture. These are important indicators.

• Joint Contractures:
• The doctor will also evaluate the joints for contractures. They’ll assess the range of motion, any discomfort the patient might have, and stiffness in the joints. These are key factors to consider.

• Examining Symptoms Related to Renal Function:
• Lastly, the doctor will examine symptoms that could point to declining renal function. These symptoms include edema (swelling), high blood pressure, and decreased urine production.

• By combining all these methods, doctors can accurately diagnose NSFs and provide appropriate treatment. It’s important to share the patient’s complete medical history and any symptoms you’re experiencing with your healthcare provider.

Biopsy: Skin or Muscle Biopsy

• When it comes to getting a final diagnosis, a biopsy of the affected skin or muscle is the way to go. Here’s what the biopsy usually reveals:

• Thicker Collagen Bundles: Fibrosis, indicated by those collagen bundles getting thicker.
• Fibroblast Proliferation: The fibroblasts, which are cells, kick it up a notch and start producing more collagen and other stuff that makes up the extracellular matrix.
• Changes in Elastic Fibers: The skin or muscle might show some deviations from the norm when it comes to its elastic fibers.

Imaging: MRI

• MRI is for checking out changes in the skin and deeper tissues. But it’s not always the go-to option because it involves potential exposure to gadolinium. So, we need to be a bit cautious and consider other imaging techniques whenever possible.

Investigations 

Lab Examinations

• Serum Creatinine Levels: High levels of serum creatinine can indicate that the kidneys aren’t functioning their best.
• eGFR (Estimated Glomerular Filtration Rate): When it comes to chronic kidney disease stages 4 and 5, patients often have a low eGFR, which tells us that their kidney function is impaired.
• Renal Biomarkers: To get a better understanding of how the kidneys are doing, we might also check out other markers of kidney function.

Pathology of the Histopathology

Now, let’s talk about how we reach that final diagnosis:

• Dermal Fibrosis: When there’s increased collagen deposition in the dermis, we call it dermal fibrosis.
• Thickened Collagen Bundles: You’ll notice that the collagen bundles in the skin or muscle tissue might be thicker than usual.
• Elastic Fiber and Fibroblast Changes: There might be some anomalies in the elastic fibers and the count of fibroblasts.

• That’s the lowdown on biopsies, imaging, lab examinations, and histopathology. Remember, these tests help us get a clearer picture of what’s going on, so we can provide the best care possible.

• Through the integration of many diagnostic methodologies and inquiries, healthcare professionals can reliably identify NSF and distinguish it from other fibrosing conditions. The improvement of patient outcomes and quality of life is contingent upon early detection and management.

Treatment 

• When it comes to treating NSF, a combination of medical supervision, physical therapy, and sometimes surgery is used. The main goals of treatment are to reduce symptoms, slow down the progression of the illness, and improve the quality of life for those affected.
•  Now let’s take a closer look at the different treatment options, including medications and surgical procedures:

Medications:

Anti-inflammatory and immunosuppressive drugs: 

• Corticosteroids like prednisone can help reduce inflammation and slow down the growth of fibrosis.
•  Another immunosuppressive medication called methotrexate can control inflammation and stop the activity of fibroblasts. 
• Mycophenolic acid is yet another immunosuppressive medication that may help decrease fibrosis.

Antifibrotic agents: 

• Pentoxifylline, a drug that improves blood flow and prevents the development of fibroblasts, can be helpful in reducing fibrosis.
• Colchicine, known for its ability to prevent tissue fibrosis, also has antifibrotic properties. 
• Imatinib, a tyrosine kinase inhibitor, has shown potential in lowering collagen deposition and fibroblast activity.

Topical Interventions 

Moisturizers and emollients: 

• Used to moisturize the skin and reduce symptoms like dryness and irritation. 

Topical steroids: 

• Applied to afflicted regions to lessen thickness of the skin and localized irritation

Pain Control NSAIDs, or nonsteroidal anti-inflammatory drugs: 

• NSAIDs like ibuprofen and others can help control pain and minimize inflammation. 
• Analgesics: In cases of extreme pain, acetaminophen or stronger painkillers may be required.

These different treatment modalities can be used to tackle NSF, with the aim of easing symptoms, slowing down the progression of the disease, and ultimately improving the quality of life for those affected.

• Physical Medicine Flexibility of Movement Exercises: To avoid contractures and preserve joint flexibility. 

• Strength training: To increase general mobility and muscle strength. Occupational therapy: To enhance quality of life and help with daily activities. 

• Methods of Surgery Indications for fasciotomy include severe joint contractures and restricted range of motion. 

Procedure: To increase joint mobility and reduce pain, the fascia is surgically released.

• Indications for Skin Grafting: Severe fibrosis and ulceration of the skin with extensive skin involvement.

 Procedure: To improve function and attractiveness, damaged skin is removed and replaced with healthy skin grafts.

• The presence of infected or ulcerated areas is an indication of diarrheal disease. 

Procedure: To encourage recovery and stop more problems, dead or contaminated tissue is surgically removed. 

• Optimizing Dialysis Increasing the frequency of dialysis sessions can aid hemodialysis patients in lowering their body’s gadolinium levels. 

• Peritoneal Dialysis Adjustments: Changing dialysis schedules to improve gadolinium clearance.

• Supportive Care Providing sufficient nutrients to promote general health and healing is known as nutritional support. 

• Stay hydrated: Sustaining adequate hydrated to promote healthy kidney function and general wellbeing.

• Monitoring and Management of Comorbid Conditions: Conditions like diabetes and hypertension should be regularly monitored and treated. 

A multidisciplinary strategy is necessary for the treatment of (NSF), including medication, physical therapy, and maybe surgical procedures to manage symptoms and enhance quality of life.

Prevention

• Immediate treatment and early detection are essential for reducing the disease’s impact.
• Reducing the occurrence of NSF requires taking preventive steps, such as avoiding or using gadolinium-based contrast agents as little as possible in high-risk patients.

• Avoidance Strategies to reduce gadolinium-based contrast agent (GBCA) exposure in people with reduced renal function are the mainstay of NSF prevention:  

• Risk assessment: Prior to giving GBCAs to patients, carefully evaluate their renal function. Patients with significant renal impairment (eGFR < 30 mL/min/1.73 m2) should not use this medication. 
• Alternative Techniques for Imaging: When feasible, use non-contrast-enhanced MRI, ultrasonography, or other imaging methods. 
• GBCAs with low risk: Use of the more recent, macrocyclic GBCAs is preferred since they are less likely to dissociate and accumulate in tissues. 
• Informed Consent: Make sure that individuals receiving GBCAs, particularly those with impaired kidney function, are aware of the dangers involved.
• Post-procedure Monitoring: In high-risk patients, close observation of renal function and symptoms after GBCA administration.
• Kidney-Associated Problems Deteriorating Renal Function: NSF has the ability to worsen pre-existing renal impairment, which can result in additional reductions in renal function and possibly a rise in the requirement for dialysis. 

Complications 

• Dialysis Complications: Individuals on dialysis may be more susceptible to blood clots, infections, and other complications associated with the treatment. 

• Discomfort: Patients’ quality of life may be greatly impacted by chronic discomfort brought on by tightness of the skin, stiff joints, and weak muscles. 
• Decreased Quality of Life: Physical restrictions, long-term discomfort, and cosmetic disfigurement can all significantly lower one’s quality of life, with implications for one’s mental and emotional health. 
• Dependency: Severe NSF cases may result in a greater need for caretakers to help with everyday tasks, which can diminish independence and put more strain on family members and medical professionals.

Prevention

• Early Detection and Monitoring: Patients who are at risk should be regularly observed for early indications of NSF, particularly if they have renal impairment. 

• choosing alternate imaging modalities wherever feasible and limiting the use of gadolinium-based contrast agents in high-risk patients. 

• Optimized Dialysis: Making sure patients receiving dialysis receive it effectively in order to lower their gadolinium levels. 

• Physical treatment: Early implementation of physical and occupational treatment is recommended to preserve muscular strength and joint flexibility. 

• Prompt Treatment: To enhance outcomes and decrease the progression of the disease, skin and joint symptoms should be treated aggressively and early.

Frequently Asked Questions 

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• Source: https://www.kidneycarecentre.in/nephrogenic-systemic-fibrosis-nsf/