About Rare Kidney Diseases

What are Rare Kidney Diseases?

1. Rare kidney diseases include more than 150 rare disorders, generally characterized by low prevalence and often with multifactorial causation; these disorders often have a major impact on kidney function and general health. Although individually rare, they collectively affect millions around the world. More than 150 rare kidney diseases are recognized; most are inherited.
2.  These conditions may be due to genetic mutations, autoimmune disorders, or environmental causes and thus may present with several symptoms and complications. 
3. Most of these disorders are inherited, having a genetic cause in 72% of instances and beginning in childhood in 70% of them. Depending on the type of disease involved, they may vary from cysts to scarring in the organs to metabolic imbalances.

Genetics happens to be a major factor in the development of rare kidney diseases.

1. Monogenic causes can be identified in approximately 20% of patients with CKD onset before age 25 and in up to 10% of adults receiving renal replacement therapy.
2. 72% of the rare diseases have a genetic cause and 70% of them begin in childhood.
3. Genetic kidney diseases involve changes in genes that affect both structure and function of the kidney.
4. They are inherited in a pattern of autosomal dominance, autosomal recessive, or X-linked patterns

Common challenges in diagnosing and managing these conditions

1. Diagnostic Difficulties: Many patients experience prolonged periods of misdiagnosis due to the rarity and complexity of these diseases, often consulting multiple healthcare providers before receiving an accurate diagnosis.
2. Management Challenges: Treatment strategies vary widely, depending on the specific condition. Management often requires a multidisciplinary approach, integrating care from nephrologists and other specialists.

Few examples 

1. Alport Syndrome: A genetic disorder characterized by kidney disease, hearing loss, and eye abnormalities, primarily affecting males.
2. Fabry Disease: An inherited condition that leads to the accumulation of a specific type of fat in various organs, including the kidneys, potentially causing kidney failure over time.
3. Cystinosis: A genetic disorder that causes harmful levels of cystine to accumulate in the body, leading to kidney damage and often requiring a kidney transplant.
4. IgA Nephropathy: A disease where IgA antibodies build up in the kidneys, causing inflammation and potential kidney failure.
5. Abnormal Hemolytic-Uremic Syndrome (aHUS): A condition that can lead to kidney failure due to blood clots in the small blood vessels of the kidneys.
6. Polycystic Kidney Disease (PKD): A hereditary disorder where fluid-filled cysts develop in the kidneys, affecting their function and potentially leading to kidney failure.

General Symptoms of Rare Kidney Diseases

While the specific symptoms can vary depending on the underlying condition, there are some common general symptoms that may indicate a rare kidney disease:

1. High blood pressure – Damaged kidneys struggle to regulate blood pressure, often leading to hypertension.
2. Fatigue – Buildup of toxins and waste products in the body due to impaired kidney function can cause extreme tiredness and fatigue.
3. Changes in urine – This includes dark urine (from blood), foamy urine (from protein), and changes in frequency or amount of urine.
4. Swelling – Fluid buildup in the body, often in the legs, feet, or around the eyes, can occur when the kidneys cannot regulate salt and fluid balance.
5. Muscle cramps – Imbalances in electrolytes like calcium and potassium can lead to muscle cramps.
6. Itchy or dry skin – Mineral imbalances caused by kidney damage can make the skin itchy or dry.
7. Back pain – Some rare kidney diseases like polycystic kidney disease (PKD) can cause pain in the lower back or sides.
8. Changes in appetite – Stomach discomfort and loss of appetite can result from toxin buildup and other effects of kidney damage.

It’s important to note that these symptoms are not specific to rare kidney diseases and can have other causes. If you experience any of these symptoms, it’s crucial to consult with a nephrologist or other healthcare provider for proper evaluation and diagnosis.

Key Diagnostic Tests

1. Blood tests: Measure levels of waste products like creatinine and urea to assess kidney function. Creatinine clearance and estimated glomerular filtration rate (eGFR) provide an estimate of how much blood the kidneys can filter per minute. Blood tests also check for anemia.
2. Urine tests: Analyze urine for the presence of blood, protein, and other abnormal substances that can indicate kidney damage. The urine albumin-to-creatinine ratio (UACR) measures the amount of albumin in the urine.
3. Imaging tests: Kidney ultrasound, CT scan, or MRI can detect abnormalities in the size, shape, and structure of the kidneys. They help identify cysts, tumors, kidney stones, or blockages.
4. Kidney biopsy: In some cases, a small sample of kidney tissue is removed with a needle to examine under a microscope. This provides a definitive diagnosis of the type and cause of kidney disease.

Diagnostic Criteria

1. Chronic kidney disease (CKD) is diagnosed if the eGFR is less than 60 mL/min/1.73m2 for 3 months or more, or if there is evidence of kidney damage (e.g. protein in the urine) regardless of the eGFR.
2. CKD is staged from 1 to 5 based on the eGFR, with stage 1 being mildly decreased kidney function and stage 5 being kidney failure requiring dialysis or transplant.
3. Acute kidney injury is diagnosed by a rapid rise in serum creatinine or reduction in urine output over hours to days.

Early detection is key, as kidney disease often progresses silently without symptoms until the later stages. Regular screening is recommended for those at high risk, such as people with diabetes, hypertension, or a family history of kidney disease.

Scenario of Rare kidney diseases in India:

1. Chronic Kidney Disease of Unknown Etiology (CKDu): CKDu has been reported in certain regions of India like Andhra Pradesh, Odisha, Goa, and Chhattisgarh, with prevalence ranging from 17-28% in affected areas. The exact cause is unknown but suspected agents include cadmium, fluoride, arsenic, pesticides, etc. 
2. Uddanam Nephropathy: Uddanam Nephropathy is a type of CKDu reported in the Uddanam region of Andhra Pradesh, with a prevalence of 17%. Occupational risk factors like exposure to pesticides have been implicated. 
3. Tondaimandalam Nephropathy: Is a newly recognized type of CKDu in the Tondaimandalam region of South India. 
4. CKDu in Supebeda, Chhattisgarh: A high prevalence of CKDu has been reported in Supebeda, Chhattisgarh. 
5. Polycystic Kidney Disease (PKD): PKD is one of the most common inherited kidney disorders, but national prevalence data is lacking for India. 
6. Glomerulonephritis: Accounts for 14% of CKD cases in the Indian CKD Registry data. 

Overall CKD Prevalence: Population-based studies estimate the overall prevalence of CKD in India to be 0.79-17.2%, with advanced CKD (stages 4-5) at 1.6-2.2%.

Management of Kidney Disease in India

Healthcare Infrastructure:

India has approximately 820 nephrologists and 710 hemodialysis units with over 2,500 dialysis stations. There are also 172 transplant centers, primarily located in South India, with most being privately operated.

The government has initiated programs to establish stand-alone hemodialysis units to increase accessibility and affordability of treatment.

Renal Replacement Therapy (RRT):

Despite the availability of RRT, only about 10% of patients with end-stage renal disease (ESRD) have access to it. Annually, around 3,500 kidney transplants are performed, with a total of approximately 700 cadaver donors.

The cost of hemodialysis ranges from USD 15 to 40 per session, while Continuous Ambulatory Peritoneal Dialysis (CAPD) costs around USD 400 per month.

Government Initiatives:

The Indian government has launched the National Organ Transplant Program to facilitate organ transplantation on a national scale and has made strides in providing government-sponsored dialysis facilities (https://dghs.gov.in/content/1353_3_NationalOrganTransplantProgramme.aspx)

 The Pradhan Mantri National Dialysis Programme aims to provide affordable dialysis services across district hospitals.

Screening and Early Detection:

Screening high-risk individuals, such as those with diabetes and hypertension, is emphasized to detect kidney disease early. Community awareness programs are being implemented to educate the public about CKD risk factors and the importance of early diagnosis.

Problems Faced in Management

Access and Affordability:

The majority of dialysis units are privately run, making treatment costly and often unaffordable for many patients, particularly those below the poverty line.

There is a significant gap between the demand for renal replacement therapy and the available services, leading to high mortality rates among patients needing treatment.

Lack of Awareness and Education:

Many patients seek medical help only when symptoms become severe, which often occurs late in the disease progression. This delay in seeking treatment hampers effective management.

There is a need for increased public awareness regarding kidney health and the importance of regular check-ups, especially for at-risk populations.

Inequitable Distribution of Resources:

Healthcare facilities and nephrology expertise are unevenly distributed across urban and rural areas, leading to disparities in access to care.

The lack of a national registry for CKD makes it difficult to assess the true burden of the disease and plan effective healthcare strategies.

Cultural and Socioeconomic Barriers:

Socioeconomic factors, including poverty and lack of education, significantly impact patients’ ability to access and afford treatment. These barriers contribute to the overall burden of kidney disease in India.

Lifestyle Modifications

• Healthy Diet: Encourage a balanced diet that limits salt, potassium, and phosphorus intake. Working with a dietitian can help tailor a meal plan that meets individual needs.
• Physical Activity: Engage in regular physical activity for at least 30 minutes most days to help manage weight, reduce stress, and improve overall health.
• Weight Management: Achieving and maintaining a healthy weight is crucial, as being overweight can strain the kidneys.
• Avoid Smoking and Limit Alcohol: Quitting smoking and reducing alcohol consumption can significantly benefit kidney health.

Blood Pressure and Blood Sugar Control

• Blood Pressure Management: Maintain blood pressure below 130/80 mmHg using medications such as ACE inhibitors or angiotensin receptor blockers (ARBs). Regular monitoring is essential.
• Diabetes Management: For patients with diabetes, optimizing blood glucose levels is critical. Regular monitoring of blood glucose and A1C levels helps manage diabetes effectively.

Medication Management

• Regular Review of Medications: Adjust drug dosages based on renal function to prevent toxicity. This includes monitoring for adverse effects and interactions with other medications.
• Anemia Management: Administer erythropoiesis-stimulating agents (ESA) and iron supplements to maintain hemoglobin levels in patients with anemia related to CKD.

Fluid and Electrolyte Management

• Monitor Electrolytes: Regularly check and manage fluid, sodium, potassium, and phosphorus levels to prevent imbalances that can worsen kidney function.

Regular Monitoring

• Routine Check-Ups: Conduct regular blood tests, urine tests, and imaging studies to monitor kidney function and disease progression.
• Patient Education: Educate patients about their condition, treatment options, dietary restrictions, and the importance of adhering to the treatment plan.

Advanced Management Options

• Dialysis: For patients with end-stage kidney disease, dialysis may be necessary to remove waste products from the blood when the kidneys can no longer perform this function.
• Kidney Transplantation: This is an option for eligible patients, involving the replacement of a diseased kidney with a healthy one from a living or deceased donor.

Multidisciplinary Approach

• Team-Based Care: Involvement of a healthcare team, including nephrologists, dietitians, and primary care providers, is essential for comprehensive management of kidney disease.

References 

1. Chronic Kidney Disease of Unknown Etiology in India: What Do We Know and Where We Need to Go
   Oommen, J., Balaji, G., Jha, A., et al. (2021). Chronic Kidney Disease of Unknown Etiology in India: What Do We Know and Where We Need to Go. ScienceDirect. Link 
2. Chronic Kidney Disease in India: Challenges and Solutions
   Agarwal, S.K., Srivastava, A. (2018). Chronic Kidney Disease in India: Challenges and Solutions. Karger. Link 
3. Chronic Kidney Disease in India
   Varughese, S., Abraham, G. (2018). Chronic Kidney Disease in India. PMC. Link 
4. What do we know about chronic kidney disease in India: first report of the Indian CKD registry
   Rajapurkar, M.M., John, G.T., Kirpalani, A.L., et al. (2012). What do we know about chronic kidney disease in India: first report of the Indian CKD registry. BMC Nephrology. Link 
5. Prevalence of chronic kidney disease in India – Where are we heading?
   Varma, P.P. (2015). Prevalence of chronic kidney disease in India – Where are we heading? NCBI. Link