Stem Cells For Kidney Disorder Treatment

About Kidney Disorder

The kidneys are bean-shaped organs that filter blood and remove waste. They are also responsible for balancing electrolytes and fluid in blood, producing hormones, and regulating blood pressure. Kidney disorders disrupt these functions and compromise the composition of blood throughout the body.

Why are kidney disorders called a "silent killer"?

Chronic kidney disease (CKD) is often referred to as a "silent killer" because it typically presents no noticeable symptoms until it reaches an advanced stage. This makes early detection challenging, underscoring the importance of recognizing warning signs and undergoing regular health screenings.

Why is blood pressure regulation vital for kidney health?

High blood pressure can damage the blood vessels in the kidneys, impairing blood flow and leading to cell death and tissue injury—the initial stages of kidney damage. Maintaining healthy blood pressure is therefore critical in preventing or slowing the progression of kidney disease.

Can kidney disorders cause other health issues?

Yes. In addition to accumulating waste products in the blood, kidney dysfunction can lead to anemia. The kidneys produce erythropoietin, a hormone essential for red blood cell production. When hormone levels drop, red blood cell production decreases, causing anemia and compounding other health problems.

The treatment options for kidney disorders eliminate the cause of disease to slow or halt its progression. For instance, treating infection resulting in the disorder or managing lifestyle to keep blood pressure in control. These modalities fail to reverse the damage already occurred in the organ. In the advanced stages, the inability to repair damage can lead to kidney failure which ultimately requires organ transplantation as the last viable alternative.

This limitation has led researchers to explore innovative treatment options. Among these, stem cell therapy has gained attention for its potential to repair damaged kidney tissue and restore lost function. Stem cell therapy for kidney failure works by addressing disease mechanisms at the cellular level, offering therapeutic effects that conventional treatments lack.

Recent advancements have enabled personalized stem cell therapies, tailored to the severity of the disorder and individual patient characteristics. This marks a shift toward precise, strategic, and potentially transformative treatments in the field of nephrology.

Diagnosis

The following diagnostic test measure kidney disorders:

GFR Test: GFR or glomerular filtration test evaluates the filtration capacity of kidneys by estimating the amount of creatinine (by product of body metabolism) in blood. According to Kidney Disease Improving Global Outcomes (KDIGO), kidney disorders can be distinguished into six stages based on GFR:

• G1: GFR 90 mL/min/1.73 m²
• G2: GFR 60 to 89 mL/min/1.73 m²
• G3a: GFR 45 to 59 mL/min/1.73 m²
• G3b: GFR 30 to 44 mL/min/1.73 m²
• G4: GFR 15 to 29 mL/min/1.73 m²
• G5: GFR less than 15 mL/min/1.73 m²

Urine Test: Healthy kidneys don’t pass albumin in urine. Therefore, urine test determine the levels of albumin in urine to detect kidney disease. Depending on albumin-creatinine ratio (ACR), there are 3 stages of kidney disorder:

• A1: ACR less than 30 mg/g (<3.4 mg/mmol)
• A2: ACR 30 to 299 mg/g (3.4-34 mg/mmol)
• A3: ACR greater than 300 mg/g (>34 mg/mmol)

Imaging: Imaging by ultrasound or computed tomography (CT) scan assess kidney size, vascular obstruction, scarred tissue, and cyst formation.

Biopsy: Kidney biopsy is an analysis of the tissue sample from kidneys to estimate the underlying causes and the severity of organ damage.

Early Signs & Symptoms of Kidney Disorder

Symptoms of kidney disorders depend on the type of kidney injury/damage.

Acute kidney injury is marked by a sudden decline in kidney function, often triggered by trauma, infection, or medication toxicity. Common symptoms include:

• Hemorrhage (unusual bleeding)
• Fever, weakness and fatigue
• Diarrhea or bloody diarrhea
• Poor appetite
• Severe vomiting
• Abdominal pain
• Back pain
• Muscle cramps
• No urine output or high urine output
• Pale skin, rash, nosebleeds
• Swelling of the tissues
• Eye inflammation
• Detectable abdominal mass

Chronic kidney disease develops gradually over time, often without noticeable symptoms in the early stages.

As it progresses, the following symptoms may appear: Poor appetite, fatigue, and vomiting

• Bone pain and/or muscle cramps
• Headache and insomnia
• Itching and/or dry skin
• High urine output or no urine output
• Decline in mental acuity
• Swelling of feet and ankles

Available Types of Kidney Disorder

Kidney disorders can arise from diverse causes and affect different parts of the organ. For example, glomerulonephritis results from damage to the glomeruli—the kidney’s filtering units—while kidney stones form due to the accumulation of minerals and salts.

Kidney damage is generally classified into two main types based on the onset and progression:

Acute Kidney Injury (AKI): AKI is characterized by a sudden decline in kidney function, typically occurring within days of an injury or harmful insult. This condition leads to inflammation and kidney cell death. However, because the damage is often temporary, recovery is possible with timely removal of the causative factor such as drug or toxin.

Chronic Kidney Disease (CKD): CKD involves a gradual loss of kidney function over months or years. In addition to inflammation and cell death, CKD is marked by the accumulation of extracellular matrix, leading to scarring (fibrosis) within the kidney. This progressive damage is often irreversible and can ultimately result in complete organ failure.

Understanding the type and underlying mechanism of kidney damage is essential for determining appropriate treatment strategies and improving patient outcomes.

What Causes Kidney Disorder?

Kidney disorders can arise from a variety of causes, which are broadly classified into pre-renal, intrinsic, and post-renal categories:

Pre-renal Causes: These originate outside the kidneys and are typically related to reduced blood flow to the organ. Insufficient blood supply deprives the kidneys of essential oxygen and nutrients, ultimately leading to functional decline. Common prerenal causes include heart failure, severe dehydration, and vascular disorders that impair circulation.

Intrinsic Causes: Intrinsic kidney disorders stem from damage within the kidneys themselves. These may involve inflammation of blood vessels (vasculitis), infections such as glomerulonephritis, genetic conditions like polycystic kidney disease, autoimmune diseases such as lupus nephritis, and hereditary disorders like Goodpasture syndrome. These conditions directly affect the kidney’s structure, leading to tissue hardening, scarring, and progressive functional impairment.

Post-renal Causes: These are due to obstructions that block the outflow of urine from the kidneys, a condition known as obstructive nephropathy. Post-renal causes include prostate enlargement, urinary tract tumors, or kidney stones, all of which can lead to increased pressure within the kidney and damage over time.

Additionally, chronic conditions such as diabetes and hypertension significantly increase the risk of kidney disease. These systemic disorders gradually impair kidney function and, if left unmanaged, can result in complete organ failure.

What are available treatments for
Kidney Disorder ?

As the damage progresses, the kidneys lose their structure and function. Treatment options generally target the cause of the disorder to prevent its progression and lifestyle management to avoid kidney injury in the future. However, they cannot repair the damage that occurred, rendering the kidneys to function at reduced capacity.

Due to their regenerative potential, stem cell treatment for kidney disorders have been gaining attention. Stem cells change the cellular level pathways in the following manner:

• Stem cells lower the levels of inflammatory cytokines like IL1β, TNFα, INFϒ, etc., while increasing the levels of anti-inflammatory factors such as IL10 and TGFα to alleviate the inflammatory pathways of the disorder.
• They differentiate into kidney cells, thus reestablishing the renal population.
• These cells also promote kidney cell proliferation by secreting bFGF, HGF, IGF, etc..
• Their anti-fibrotic and angiogenesis properties exert protective and regenerative effects on the kidneys.
• These cells inhibit cell death by decreasing activation of p53, NH-2 terminal kinase, c-Jun, etc.
• They release VEGF and bFGF for blood vessel remodeling, which is effective in vascular causes of kidney failure.
• These cells also alleviate autoantibodies and increase the production of regulatory T cells that control autoimmunity. This effect is particularly beneficial in kidney disorders arising from autoimmune disorders.
• The antioxidant and anti-inflammatory properties of stem cells exert anti-fibrotic effects on the organ.

Frequently Asked Questions

Q1. Is stem cell therapy effective for kidney disorders?

Preclinical research and early clinical trials have demonstrated the effectiveness of stem cell therapy for chronic kidney and acute kidney disease. Stem cells drive cell regeneration and prevent further damage through their myriad therapeutic properties.

Q2. How are stem cells injected to treat kidney disorders?

Stem cell infusion, including dose, time interval, and administration route, depends on the treatment plan personalized to the patient. Generally, two administration routes—intravenous and intra-arterial (injection into the kidney artery)—are preferred for infusion into the kidney. The procedure is performed in a minimally invasive manner by a trained medical professional.

Q3. Which cells are used for stem cell treatment for Chronic Kidney Disease?

Clinical trials for CKD treatment have focused on mesenchymal stem cells (MSCs) for treating kidney disorders. Among various sources of MSCs, the umbilical cord has received more attention due to its higher regeneration potential, easy accessibility, painless extraction, and availability as an “off-the-shelf” therapy.

Q4. How much time will be required to notice improvements after stem cell therapy for CKD?

The degree of improvement and the time it takes to observe them vary from person to person. It also depends on the severity of organ damage and the patient’s overall health, including any comorbidities. Gradual improvements might be noticeable in the initial period, with the full benefits realized in a few months.