A New Regenerative Solution To Chronic Kidney Disease

Chronic Kidney Disease: Is it a Growing Global Concern?

What if we tell you that one of the world’s fastest-growing health challenges is progressing silently among a huge population?  

Chronic kidney disease (CKD) progresses with time (at least 3 months), where the kidney’s function is altered. Kidneys become incapable of performing their normal jobs- filtering out harmful toxins, wastes, or extra water. They also help in red blood cell formation, maintaining adequate blood pressure and maintaining electrolyte balance in the blood. Compromised kidney function means a buildup of waste in the blood. 

Globally, 10% of the population is affected with Chronic Kidney Disease, among whom millions die from lack of accessible treatment [1]. Though it is true that not every individual with CKD experiences kidney failure, progression is worsened without early treatment.  

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Understanding Chronic Kidney Disease

How do Kidneys Function at the Cellular Level?

The human body has two kidney-shaped kidneys located towards the back. The key functions include:

• Removal of waste and extra water from the body 
• Maintains electrolyte and mineral balance
• Boost production of red blood cells
• Maintain bone health
• Helps maintain blood pressure 

What is Chronic Kidney Disease (CKD)?

In CKD, the kidneys get damaged, which increases the risk of developing other chronic conditions like hypertension or cardiovascular disease. chronic kidney disease stages have 5 distinct levels depending on glomerular filtration rate (GFR) (measurement of how well kidney filters one’s blood):

• Stage 1: GFR occurs at 90ml/min or higher. Here, the kidney functions well but has mild damage symptoms.
• Stage 2: GFR goes down to 60ml/min-89ml/min. Increased sign of kidney damage
• Stage 3: In 3a, GFR occurs between 45 and 59ml/min. In 3b, GFR occurs at 30 and 44ml/min. Kidney function is compromised. The symptoms mostly appear at the 3a stage. Adequate treatment can restrict individuals from further advancement.
• Stage 4: GFR between 15-29 ml/min. Kidney function becomes very poor; it’s almost nonfunctional.
• Stage 5: GFR <15ml/min. Complete kidney damage or failure can occur at any time. Individual relies on dialysis or transplantation is required. 

What are the Signs and Symptoms of CKD?

The common symptoms of CKD include:

• Frequent peeing tendency
• Fatigue, tiredness, loss of appetite
• Swelling on the hand, feet or ankles
• Breathlessness and skin issues
• Insomnia
• Itchy skin
• Causes of Chronic Kidney 

What are the Causes of CKD?

Causes of chronic kidney disease include:

• Diabetes Mellitus and Diabetic Nephropathy significant reduces GFR, persistent albuminuria
• Hypertension leads to fluid retention, creates hypertensive nephrosclerosis, and leads to vascular Damage
• Chronic Glomerulonephritis, where the glomeruli inside the kidney are damaged
• Polycystic Kidney Disease, a genetic condition where fluid-filled cysts grow in kidney
• Long-Term medication intake, such as nonsteroidal anti-inflammatory drugs (NSAIDs) or pain killers
• Recurrent Infections and Obstructive Disorders

How is CKD Diagnosed?

The nephrologist orders certain blood and urine tests that include the determination of:

• GFR shows how efficiently kidney is filtering the blood
• Serum creatine level, creatine is a muscle metabolic waste product, a high creatine level shows inefficient function of creatin
• Urine test to determine protein (albumin) and blood in pee
• Some other imaging based test includes ultrasound, MRI, CT or biopsy

How is CKD Treated?

Chronic Kidney Disease Treatments involve certain approach including:

• Medications– Certain medications including angiotensin-converting enzyme (ACE) inhibitors, angiotensin receptor blockers (ARBs), phosphate binders, erythropoietin, Vitamin D and calcitriol
• Kidney Dialysis– Dialysis involves using machines that remove waste products from the body.  There are two types of dialysis: hemodialysis (a patient’s own blood is circulated through a machine, waste material is removed, and blood is returned to the body). Peritoneal dialysis (dialysis solution is directly placed in the abdomen via a catheter, where the solution absorbs waste products and is removed)
• Kidney transplant– this involves replacing an unhealthy kidney with a healthy kidney.
• Lifestyle and Dietary management– maintaining blood sugar and blood pressure, along with dietary intervention, is key in CKD management. Some foods, including limiting protein intake, reducing cholesterol level, and limiting sodium and potassium in diet, create less strain on kidney function. 

However, all the above conventional treatments deal with managing the disease symptoms. Researchers in the past decade have explored the regenerative approach that can bring change from within. 

What Changes does the Regenerative Approach Introduce in CKD?

Stem cells, especially mesenchymal stem cells (MSCs), possess regenerative capability. The cells can differentiate into specific cell types along with paracrine signalling ability. This has made stem cells an ideal candidate for introducing repair and regenerating damaged cells/tissue in CKD. Stem cells in the kidney repair work with the following mechanism:

• Regeneration and Repair of Kidney Cells: Stem cells differentiate into kidney-specific cells like renal tubular cells, podocytes, etc. These aid in repair and regeneration
• Anti-Inflammatory Effect: Stem cells secrete various bioactive molecules like anti-inflammatory molecules that reduce inflammatory, one of the major contributor in kidney disease progression
• Immunomodulation: MSCs possess the ability to modulate immune response, potentially reducing the risk of immune rejection
• Paracrine Effect: MSCs secrete various growth factors and cytokines that potentially promote the repair of surrounding tissues. This improves kidney function.

Current Research & Clinical Trials in Regenerative Nephrology

• Clinical Trial Phase 1 (NCT05362786) using MSCs for CKD. The intravenous delivery of allogeneic MSCs in CKD patients. The study determined safety and tolerability in a dose-dependent manner [2].
• MSCs-derived extracellular vesicles in CKD patients. Early studies reflected improvement in renal functional markers (eGFR, creatinine), and modulation of inflammatory response [3]
• Research with bioactive scaffolds and extracellular vesicles on animal models with kidney injury demonstrated structural kidney regeneration. These preclinical trials are shaping the design of regenerative nephrology in human trials [4].

What are the Challenges in Transforming Regenerative Approaches into Therapeutics?

• Source of Cells and Quality: Determining the optimal source of obtaining stem cells and maintaining quality consistency is important
• Administration Method: Developing an effective method for administering stem cells for maximizing therapeutic benefits
• Safety and Efficacy: Large-scale clinical trials for determining long-term safety are important. Research mitigating potential risk with stem cell use, like tumorigenicity or adverse immune response, is important.
• Regulatory and Ethical Concerns: The use of stem cells for therapeutic purposes is subjected to complex regulatory and ethical considerations. Addressing such concerns to facilitate clinical application is crucial. 

”Did You Know” About CKD?

• Silent Progression: In the early stages (1 and 2), patients show negligible symptoms.
• Main Causes: Diabetes (diabetic nephropathy) and hypertension are leading comorbid factors potentially leading to CKD.
• CKD shares a strong link with the immune system and systemic inflammation that hinders the body’s ability to heal itself 

”Did You Know” About Stem Cell Therapy for CKD?

• Not a Replacement (Yet): Stem cell therapy is currently at an experimental stage
• Stem cell treatment is under clinical trial, used as add on treatment across many clinics.
• MSCs are the primary choice for kidney cell repair, reducing systemic inflammation and creating supportive conditions by releasing growth factors.  
• Early intervention potentially prevents the progression of CKD, introduces cell regeneration, reduces fibrosis, and induces an anti-inflammatory effect
• In India, 60-80% of the stem cell-based research for CKD showed a positive response

*NOTE: Use of superior quality stem cells ensures safety and efficacy of the treatment. Advancells, Noida, India, is among the leading stem cell research laboratories that culture and maintain superior quality stem cells for nephrology research. 

Conclusion

CKD is a silently progressing, life-threatening disease. The regenerative approach potentially lays a curative solution. Early diagnosis and intervention show effectiveness in slowing and prevention in disease progression.

Chronic Kidney Disease Patient Success Stories

References

1. National Kidney Foundation (NKF). Chronic kidney disease (CKD) – symptoms, causes, treatment. National Kidney Foundation; 2023. Available from: https://www.kidney.org/kidney-topics/chronic-kidney-disease-ckd
2. Mayo Clinic. Bone marrow–derived mesenchymal stem cell therapy for chronic kidney disease. ClinicalTrials.gov Identifier: NCT05362786. Available from: https://clinicaltrials.gov/study/NCT05362786
3. Quaglia M, Merlotti G, Colombatto A, Bruno S, Stasi A, Franzin R, Castellano G, Grossini E, Fanelli V, Cantaluppi V. Stem cell-derived extracellular vesicles as potential therapeutic approach for acute kidney injury. Frontiers in Immunology. 2022 Mar 10;13:849891.
4. Cha SG, Rhim WK, Kim JY, Lee EH, Lee SY, Park JM, Lee JE, Yoon H, Park CG, Kim BS, Kwon TG. Kidney tissue regeneration using bioactive scaffolds incorporated with differentiating extracellular vesicles and intermediate mesoderm cells. Biomaterials Research. 2023 Dec 5;27(1):126.

FAQ’s

Q- Can CKD be Cured?

Currently, CKD treatment focuses on preventive measures. With the emergence of regenerative therapeutics, a complete cure is potentially possible in the future.

Q- Is Regenerative Therapy for CKD Safe?

Yes, regenerative therapy to date has shown safety and efficacy with the use of MSCs for CKD patients. Currently, there is a need for large-scale clinical trials to determine long-term safety.

Q- When is Dialysis Necessary in CKD Patients?

Patients at Stage 5 with CKD, or who have a GFR <15ml/min, require dialysis. Common symptoms include fluid overload and symptoms of uremia.