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A Literature Review of Liposorber treatment with Focal Segmental Glomerulosclerosis:

A Successful Intervention in Comparison to Chemotherapy Treatment.

Nikole Hardy, Ty Hundley, Danielle Huffman, Leialae Kanan

School of Nursing, Old Dominion University

NURS 363: Principles of Practice: Research as Foundation for Practice

Dr. Jamela Martin

July 15, 2022

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Literature Review of Liposorber treatment with Focal Segmental Glomerulosclerosis:

A Successful Intervention in Comparison to Chemotherapy Treatment.

Focal Segmental Glomerulosclerosis (FSGS) is a rare disease that attacks the glomeruli

of the kidneys that can lead to permanent kidney damage, kidney failure and can cause a serious

condition called Nephrotic Syndrome (Nephcure, 2021). FSGS is also a major cause of end stage

renal disease. A better understanding of the molecular basis of the disease can provide better

insight into forming therapeutic regimens (Potter, 2019). A common treatment for FSGS is

chemotherapy treatment but studies have led to the use of Liposorber treatment as an alternative.

This paper will focus on what FSGS is, different treatments for the disease while mainly

focusing on the comparison of benefits of Liposorber treatment versus chemotherapy for

treatment of FSGS, and that literature shows that liposorber is an effective treatment with Focal

Segmental Glomerulosclerosis as an alternative therapy to chemotherapy treatment.

Focal Segmental Glomerulosclerosis Patients

FSGS as a Disease

The glomeruli is the part of the kidney that filters the blood. In FSGS some of the

glomeruli are damaged but if this damage is not controlled it can lead to kidney failure. There are

six types of FSGS: primary, adaptive, genetic, viral, medication induced, and APOL 1-

associated. This disease is most common in African American males and rates of the disease

have been increasing which is thought to be directly related to chronic inflammation and obesity

(Rosenberg, 2017). Some patients are asymptomatic but there are several symptoms that have

been observed in individuals. Edema that is most noticeable around the eyes, hands, abdomen

and feet which also leads to weight gain, hypertension, hyperlipidemia, proteinuria,

hypoalbuminemia and high creatinine levels in the blood (Nephcure, 2021). The most common

symptoms include nephrotic syndrome which is characterized by edema, fatigue, loss of appetite,
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pleural effusion, abdominal pain, and hypertension (Sreepada, 2020). There has been a steady

increase in the incidence of primary FSGS over the last 20 years. In most reports of adult patients

that have appeared in recent years, there has been a 2–3 fold rise in the rate of diagnosis of the

disease (Kiffel, n.d.). In the United States 40,000 patients have FSGS and 60% do not respond to

treatment. 50% of these patients will progress to end stage kidney failure. There are about 1,000

FSGS patients that receive a kidney transplant and unfortunately FSGS returns 30-50% of the

time. FSGS is estimated to be responsible for 40% of adult nephrotic syndromes and 20% of

pediatric nephrotic syndromes and has an incidence of 7 per million. FSGS has an estimated

prevalence of 4% and is the most common primary glomerular disease resulting in end-stage

renal disease in the United States (Sprangers, 2016).

Common Treatments For Focal Segmental Glomerulosclerosis

The short term goal of treatment is to stop protein spillage or to lower the amount of

protein lost in the urine. The long term goal is preventing any further kidney damage and

preventing a relapse (Nephcure). The goal of pharmacotherapy is to preserve renal function,

reduce morbidity, and prevent disease complications in this common cause of primary

glomerular disease in adults. A simple intervention for this disease includes lifestyle changes

that the individual can make. FSGS causes podocyte injury that creates a kidney malfunction so

it is important that the individual’s blood pressure should be maintained within acceptable ranges

and one intervention for that is by following a low sodium diet (Beaudreuil, 2017). Common

medications prescribed for treatment include immunosuppressives, glucocorticoids, rituximab,

(Rosenberg) calcineurin inhibitors and plasmapheresis (Beaudreuil). With primary or secondary

FSGS with proteinuria the initial treatment is angiotensin-converting enzyme inhibitors (ACEIs)

or angiotensin receptor blockers (ARBs). If this treatment does not work they may require more
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aggressive treatment such as prednisone or immunosuppressive agents (Sreepada).

Unfortunately, some forms of FSGS can become steroid-resistant which requires various

alternative treatments including liposorber or chemotherapy treatment (Beaudreuil).

Unfortunately, while there are many risk factors that are known for this disease there is no

specific known cause and the diagnosis of FSGS is found by undergoing a kidney biopsy.

Typically blood work to evaluate how well your kidneys are still functioning, urine tests to check

for blood and protein in the urine, and genetic testing to try to determine a cause are usually

performed as well. (The American Kidney Fund, 2022)

Liposorber treatment

Liposorber treatment is the blood purification therapy that removes malignant

lipoproteins including low density lipoproteins from circulating the blood flow. It can also

rapidly reduce cholesterol levels. FSGS carries a tough prognosis and is resistant to most

steroids. Liposorber apheresis is a therapeutic approach to fight drug resistant FSGS and post

renal transplants to prevent the recurrence of FSGS (Frontiers in Pediatrics, 2022). FSGS

reoccurs in 30-40% of renal transplant patients, causing injury in 20-30%, and graft loss in 40-

50%. FSGS is the number one current reason that children face graft loss (Frontiers in Pediatrics,

2022). FSGS develops rapidly and frequently. A kidney transplant may seem like a great idea.

However, the recurrence rate is very high. Over half of the patients with recurrent FSGS in their

transplant will lose their kidney within 5 years. Of all the patients with FSGS who get a kidney

transplant, about 15% will lose the kidney due to recurrent FSGS (UNC, 2018). It is already an

excruciating process to get on the waitlist for a transplant and to have received one and it fails is

devastating mentally and physically. That is what led them to research the use of liposorber
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treatment before a kidney transplant. Low density lipoprotein adherence before kidney transplant

in FSGS patients is used to prevent the recurrence.

A study was conducted by the institutional review boards at Toko Women’s Medical

University, Tokyo. Five adult patients with FSGS underwent liposorber treatment before having

a living related donor kidney transplant. In all five patients the LDL cholesterol was all within

normal range. In case 2 urinary proteins increased. After five months post transplant another

urinalysis was performed to show urinary proteins remained normal. The graft survived with no

rejection reactions with any of the five patients and in addition there were no signs or symptoms

of recurrence of FSGS (Sannomiya, 2018). Another study was conducted using 17 adult patients

diagnosed with FSGS who were drug resistant or drug intolerant. The results showed an

improvement in the response rates to steroids or an immunosuppressive therapy and it concluded

with a partial or complete remission with patients with FSGS (Frontiers in Pediatrics, 2022). The

study provided improvement in the response rates to steroid or immunosuppressive therapy and

induced complete or partial remission of proteinuria in some patients with drug resistant primary

FSGS. These findings indicate the importance of early detection of the disease and referral in the

prognosis of FSGS (Ossareh, Yahyaei, Asgari , & Afghahi , 2020).

Liposorber treatment used with children diagnosed with Nephrotic syndrome

In the last few years, studies have reported an increase in frequency of focal segmental

glomerulosclerosis (FSGS) and a resistance in corticosteroid resistance without a similar increase

of FSGS (Narla & Swiateacka-Urban , 2020 ). 80% of children with nephrotic syndrome respond

to steroids. Liposorber is being evaluated as a potential solution to placing the remaining 20% of

children with nephrotic syndrome into remission. Liposorber (LDL-A) was able to decrease lipid

levels and induce complete or partial remission in the majority of patients. It therefore should be
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considered in pediatric patients with treatment resistant SRNS to prevent kidney disease

progression. LDL-A was able to significantly decrease the lipid levels in patients. Current studies

showed the glomerular sclerosis burden was less likely to respond (Al-mousily, 2021). When

liposorber treatments were being tested scientists were not expecting for the drug to place

patients into remission however, it did. It was used when every form of treatment was successful.

Once using the LDL-A patients saw a great decrease in the patients protein to creatinine ratio.

The machine used is available in most cities for it is also used for severe lymphedema. It is now

a FDA approved treatment for pediatric FSGS (Al-mousily, 2021).

Effects of Liposorber Treatment versus Chemotherapy

Primary FSGS commonly progresses to end-stage renal disease if left untreated due to its

poor prognosis. End-stage renal disease typically occurs two to eight years after initial diagnosis.

FSGS is a difficult disease to manage, while some patients undergo kidney transplants and

achieve complete or partial remission with various medications, patients commonly relapse.

Corticosteroids are the most common and effective therapy that has been used to achieve

remission. However, remission rates are only 20-50%. The use of corticosteroids also raises

concern due to adverse effects related to prolonged use. Hypertension, growth impairment, and

immune suppression commonly develop after much use causing further problems and disease

(Frontiers in Pediatrics, 2022). Liposorber treatment and chemotherapeutic agents, such as

Rituximab, have been studied for their effectiveness in managing FSGS and remission rates.

While these treatments need further evaluation, they are likely to become beneficial in the care of

FSGS.
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Liposorber

Liposorber treatment has been proven useful for pediatric patients and is being

considered as an upcoming treatment in NS and FSGS. It helps prevent the progression of kidney

disease by decreasing lipid levels and inducing partial or complete remission. It is becoming a

therapeutic approach for drug resistant FSGS and for patients who are recovering from a post-

renal transplant. Liposorber therapy is a form of blood purification that removes VLDL, LDL,

and triglycerides without affecting the serum HDL levels, therefore, reducing the lipid levels and

increasing kidney function. Liposorber treatment produced favorable outcomes. Due to the

reduction in lipid levels, response to steroids and calcineurin inhibitor therapy improved. There

was proven to be better blood flow and vasodilation, as well as anti-inflammatory effects (Raina

et al., 2022). According to a study performed by Frontiers in Pediatrics, patients who were

younger than 21 with drug resistant or intolerant NS with primary FSGS received 12 sessions of

Liposorber treatment over a span of 9 weeks. These patients were followed up with at 1,3,6,12,

and 24 months after completion of treatments. The study concluded that partial and complete

remission rates of NS at 1,3,6,12, and 24 month follow up were 14.3,50,66.7, 50, and 100%.

During the follow-up period, improvement or stable eGFR in all patients was noted. However,

there were limitations to this study due to the small number of subjects and high dropout rate.

Another study incorporated Liposorber treatment in combination with prednisolone. The

combination therapy induced partial and complete remission of NS in 7 out of 11 children at 1

month follow up. Out of those seven, five reached complete remission and had normal kidney

function for years after. To conclude, Liposorber treatment may be best for FSGS in combination

with steroids (Raina et al., 2022). Maximum benefit can also be achieved if Liposorber treatment
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is initiated early in the disease process due to better response rates, patients with a more severe

case of sclerosis are less likely to respond (Raina et al., 2022).

Chemotherapeutic Agent: Rituximab

Rituximab is being considered as an additional treatment for FSGS, with a goal of

reducing the use of steroids. Adding an immunosuppressive agent with a steroid as a treatment

option for FSGS would hopefully decrease adverse effects and reduce the relapse rates.

Rituximab is FDA approved for B-cell malignancies and connective tissue diseases, due to its

role in B-cell independent mechanisms (Hansrivijit et al., 2020). Rituximab also plays a role in

the function of podocytes, which is pivotal since FSGS is a rare podocytopathy (Elsevier, 2020).

Rituximab is used as an antibody to bind to CD20-positive lymphocytes. It is suggested that it

induces remission via two pathways. CD20 positive B cells are involved in the

immunopathogenesis of FSGS by the production of the circulating permeability factors, which

disrupt podocyte integrity. Rituximab also reduces the exposure to B-cell-induced local

interleukin-4, which causes foot process effacement and proteinuria (Zhong et al., 2022).

Research for rituximab included 16 different studies, with 221 patients. These studies included

patients older than 18 years of age, diagnosed with steroid resistant, frequent relapsing, or steroid

dependent disease. All patients were treated with rituximab with a median dose of 1500 mg/m2.

Findings based on 51 of these patients included an overall remission rate of 53.6%. Complete

remission was 42.9% and partial remission was 10.7%. The relapse rate of FSGS was 47.3%.

The dosage of rituximab did not affect the remission or relapse rates. To conclude, rituximab

reduced the number of relapses per year from 1.3 to 0 and significantly reduced the levels of

proteinuria and serum albumin. (Hansrivijit et al., 2020). Other research states rituximab

treatment is a promising regimen when taken with steroids, such as prednisone, to reduce relapse
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rates. It is also associated with lower frequency post-transplant nephrotic range proteinuria

(Elsevier, 2020). While these are promising findings, it is likely rituximab responds better to

mild disease and later diagnoses. Rituximab is likely to remain a second-line treatment due to its

high cost, (Zhong et al., 2022), but may remain a priority for patients with complex prognoses or

contraindications to first-line treatments (Elsevier, 2020).

Outcomes

Improvement of Symptoms

A main outcome accomplished by treatment for FSGS is the improvement of symptoms

causing Nephrotic Syndrome. The symptoms of Nephrotic Syndrome as stated above include

edema, fatigue, loss of appetite, pleural effusion, abdominal pain, and hypertension (Sreepada,

2020). Other symptoms of Nephrotic Syndrome include hypoalbuminemia, hyperlipidemia, and

proteinuria (NIDDK, n.d.). The improvement of these specific symptoms were monitored in

these studies. A study across four different pediatric centers monitored baseline proteinuria and

glomerular filtration rate to post treatment results, “patients demonstrated improvements in their

estimated GFRs at their most recent follow-up since LDL-A discontinuation” (Al-Mousily,

2021). Lipid levels were also monitored, LDL-A was successful at significantly reducing LDL,

total cholesterol, and triglyceride. The patients treated using LDL-A were found to have

improvement in their urine protein excretion, hyperlipidemia, hypoproteinemia, and renal

function as a result of this treatment. This suggests that LDL-A may therefore be an effective

therapy for nephrotic syndrome due to collapsing FSGS. Two patients at Nippon Medical School

Chiba Hokusoh Hospital achieved remission of Nephrotic Syndrome after LDL-A treatment.

Furthermore, the study following these patients concluded it is possible that early additional
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LDL-A is effective for patients with Acute Kidney Injury and drug-resistant Nephrotic

Syndrome (Terada, 2020).

Improved Rates of Remission

Another outcome accomplished by these treatments of FSGS is the improved rate of

remission. Partial remission (PR) is defined as urine protein to

creatinine ratio (UPC) of 0.2-2 (g/g) or decrease in UPC ≥ 50%, and

complete remission (CR) is defined as UPC < 0.2 (g/g). A study of FSGS

patients treated with rituximab resulted in a total remission rate of 19 out of 33 cases (Zhong,

2022). The Tokyo Women’s Medical University, followed 16 patients who were less than 16

years at the age of onset and had post-transplant recurrence of FSGS from 1993 to 2018. The

time period for remission was defined as the time from initiation of plasma exchange to

remission achieved by the end of treatment for recurrent FSGS. Ten patients were responders,

and six patients were non-responders. Univariate analysis showed that responders had a

significantly lower amount of maximum proteinuria at the time of recurrence (P = 0.015) and

more highly selective proteinuria (P = 0.013) than non-responders. The time to remission from

initiation of therapy was 2 months (interquartile range 0.2–4.4). In all responders, except for one

patient, remission was achieved within 6 months (Ban, 2021).

In a study of patients using LDL-A, Liposorber treatment, LDL-A was able to

significantly decrease the lipid levels in these patients and induce CR and PR in the majority.

(Al-Mousily, 2021). LDL apheresis (LDL-A) is now FDA approved for the treatment of

pediatric focal segmental glomerulosclerosis (FSGS). Effective management of hyperlipidemia

with LDL-A in SRNS patients may prevent progression of kidney disease and lead to remission.

At one-month follow-up, 1 of 7 patients attained partial remission of Nephrotic Syndrome while

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2 of 4 subjects, and 2 of 3 subjects had partial/complete remission at 3- and 6-months follow-up,

respectively. One of two patients followed up for 12 months had complete remission and one

patient had partial remission of NS after 24 months. Improved or stable eGFR was noted in all

patients over the follow-up period (Al-Mousily, 2021).

Conclusion

When analyzing different treatments for Focal Segmental Glomerulosclerosis, Liposorber

therapy and Chemotherapy are commonly used; however, a common question might lead to

which therapy is better? The purpose of this literature review paper was to utilize, analyze, and

interpret the data collected from multiple sources about liposorber treatment versus

chemotherapy. Based on our research, literature shows that liposorber is an effective treatment

with Focal Segmental Glomerulosclerosis as an alternative therapy to chemotherapy treatment.

The outcomes of Liposorber treatment showed improvements of symptoms causing Nephrotic

Syndrome as well as improvement in rates of remission. Although both therapies have their

benefits and risks, it’s ultimately up to the patient and care team to collaborate and find the most

effective treatment for them.

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