Understanding Polycystic Kidney Disease: Guest Column by Dr Francisco Salcido-Ochoa

Dr Francisco Salcido-Ochoa on ADPKD

Polycystic Kidney Disease is a relatively common disorder that is usually hereditary. 

Medical Channel Asia invites Dr Francisco Salcido-Ochoa, distinguished renal specialist and transplant immunologist and founder of Francisco Kidney & Medical Centre, to explain the intricacies of Polycystic Kidney Disease. 

What is Polycystic Kidney Disease?

Autosomal Dominant Polycystic Kidney Disease, commonly referred to as ADPKD or simply Polycystic Kidney Disease, stands as a notable hereditary condition stemming from genetic mutations responsible for maintaining the intricate structure of our kidneys. While statistical prevalence varies globally, it is estimated that around 5 to 10 cases per 10,000 births are affected by this condition – a figure that places it within the realm of relatively common disorders.

These genetic mutations initiate a gradual distortion of the microtubules within the kidneys, the very pathways through which urine’s precursor would normally navigate. Over time, this anomaly prompts the formation of balloon-like structures termed cysts, each harbouring a fluid of its own. These cysts multiply and expand with the passing years, resulting in progressive enlargement of the kidneys over the span of decades. Unfortunately, this physical growth doesn’t translate into improved functionality; instead, kidney function tends to decline as the condition advances.

How does someone get Polycystic Kidney Disease?

Polycystic Kidney Disease is intricately tied to genetic inheritance. This hereditary condition operates within established genetic patterns and is passed down through familial lines. However, it’s important to note that not all family members will necessarily be affected by the disease.

Think of our genetic makeup as a blueprint, a complex code governing our biology. Within this framework, abnormalities can arise. In the case of Polycystic Kidney Disease, the prevailing abnormality often involves chromosome 16, which is implicated in roughly 80% of cases. This genetic variation sets in motion the development of cysts within the kidneys, contributing to the clinical manifestations of the disease. Interestingly, those harbouring this specific genetic irregularity tend to experience a more challenging disease course in comparison to individuals with an alternate mutation found on chromosome 4 – the second most prevalent genetic aberration associated with the condition. Furthermore, a subset of cases stems from mutations occurring in other genetic components.

An intriguing aspect of Polycystic Kidney Disease is its sporadic occurrence. In some instances, an individual develops a genetic mutation that marks the origin of the disease within their family. While not inherited from previous generations, this mutated genetic code can be passed on to descendants.

It’s crucial to dispel any misconceptions: Polycystic Kidney Disease is distinct from conditions influenced by lifestyle factors such as type 2 diabetes; it doesn’t share the characteristics of autoimmune disorders; nor can it be transmitted like an infectious ailment. Instead, it stands as a testament to the intricate interplay of genetics.

What are the Risk Factors Associated with Faster Disease Progression in Polycystic Kidney Disease?

The advancement of Polycystic Kidney Disease hinges on a multitude of determinants that warrant comprehensive consideration. These factors intricately interplay, shaping the trajectory of the disease:

Genetic Mutation Profile: The foundation of genetic composition assumes prominence. The nature of the genetic mutation responsible for polycystic kidneys emerges as a pivotal determinant. Patients harbouring mutations in chromosome 16 often face a heightened risk of accelerated disease progression, contrasting those with mutations in chromosome 4.

Familial History of Early Kidney Failure: A hereditary legacy assumes significance. Individuals with a familial precedent marked by premature total kidney failure encounter a heightened likelihood of facing an expedited disease course.

Gender Disparity: Gender introduces an unexpected dimension. Males, unfortunately, grapple with a more aggressive disease trajectory compared to their female counterparts.

Kidney Size: The dimensions of the kidneys come into play. Enlarged kidneys paradoxically predict an unfavourable prognosis. Advanced techniques, such as magnetic resonance imaging (MRI), offer the capacity to precisely quantify kidney volume, providing invaluable prognostic insights.

Proteinuria (the presence of protein leakage in urine): Proteinuria amplifies the risk of hastened disease progression, introducing a layer of complexity.

Bleeding kidney cysts: A history of cystic bleeding elevates the risk of an accelerated disease course.

Sodium Excretion in Urine: Sodium homeostasis influences disease progression. Elevated sodium excretion in urine is linked to an escalated risk of accelerated advancement.

Concomitant Kidney Conditions: Concurrent battles come to the forefront. Patients contending with additional kidney-affecting conditions, particularly when inadequately managed, experience an intensified disease progression risk. Common culprits like hypertension and diabetes mellitus, or less frequent contenders like glomerulonephritis, contribute to the complex interplay.

Nephrotoxic Drug Usage: Medication considerations offer a cautionary narrative. Nephrotoxic drugs, typified by certain non-steroidal anti-inflammatory drugs (NSAIDs) like ibuprofen, naproxen, diclofenac, celecoxib, etoricoxib, etc can affect kidney function. Prudent decision-making is imperative, necessitating consultation with healthcare professionals to ensure the compatibility of painkillers with kidney health.

Nephrotoxic Imaging Agents: Imaging procedures warrant vigilance. The utilization of nephrotoxic agents during imaging studies, such as radio-contrast agents in computed tomographies (CTs), introduces a risk factor that may contribute to expedited total kidney failure.

Navigating the intricate matrix of these risk factors is pivotal in comprehending and managing the dynamic clinical course of Polycystic Kidney Disease. Consultation with medical experts and meticulous adherence to personalized care plans emerge as fundamental in shaping the course of this complex condition.

What Are the Symptoms of Polycystic Kidney Disease?

The presentation of symptoms in individuals with polycystic kidney disease can exhibit a diverse spectrum, with some remaining asymptomatic during the initial stages. Discovery often unfolds through:

Screenings and Assessments: Many cases come to light during routine health evaluations, triggered by indications such as high blood pressure, protein or blood leakage in urine, or potential kidney abnormalities.

Incidental Findings: Diagnostic imaging, like ultrasound, undertaken for unrelated reasons may unveil the presence of polycystic kidney disease.

Familial Vigilance: Individuals with a family history of the condition might opt for proactive investigation, involving kidney imaging or genetic testing.

However, as the condition advances, manifestations can become more pronounced:

Kidney Enlargement: The expanding kidneys can encroach upon neighbouring organs within the abdominal cavity, contributing to sensations of bloatedness and discomfort.

Symptoms of Advanced Kidney Disease: A considerable number of patients ultimately experience a decline in kidney function until total kidney failure, giving rise to symptoms commonly associated with advanced kidney disease. These include fatigue, malaise, itchiness, nausea, vomiting, lack of appetite, and weight loss. Fluid retention can manifest as leg swelling and shortness of breath, while excessive thirst might occur due to inadequate urine concentration. In addition, blood pressure management becomes increasingly challenging as the disease advances, potentially exacerbating hypertension.

Complications and Pain: Cyst rupture is an occasional complication, giving rise to flank pain and blood in the urine. Chronic pain, often stemming from kidney enlargement and increased tension on the kidney’s covering (capsule), is another facet. Pain can also arise from tension on the main urinary tube (ureter) or the kidney’s blood vessels, caused by overstretching.

Extrarenal Organ Involvement: Polycystic Kidney Disease can extend its impact beyond the kidneys. Cysts may form in the liver, pancreas, and epididymis (adjacent to the testicles). Notably, the brain can be affected, potentially leading to aneurysmal dilations in cerebral arteries, resulting in headaches or even critical ruptures. The gastrointestinal tract may develop diverticula, sack-like protrusions that can lead to infections, bleeding, or rupture. Abdominal hernias, marked by protrusion through a weakened abdominal wall, can also emerge, potentially causing discomfort or complications. The condition can affect the cardiovascular system, contributing to valve disorders or aneurysms in coronary arteries, bearing the risk of rupture with potentially severe consequences.

Understanding these multifaceted symptoms and potential complications is essential in comprehending the intricacies of Polycystic Kidney Disease. Timely consultation with healthcare professionals and vigilant management remain paramount in navigating this complex landscape.

All these potential findings need to be taken into consideration when evaluating patients with polycystic kidney disease. The exclusion of brain aneurysms is crucial for patients who are considered for kidney transplantation.

How Is Polycystic Kidney Disease Diagnosed?

The diagnostic path for Polycystic Kidney Disease varies based on factors such as family history and presenting symptoms. Here is a comprehensive overview of the diagnostic process:

Family History: The diagnostic journey is often simplified when there is a familial history of the disease. This insight can guide healthcare professionals in their assessment.

Imaging Studies: Diagnosis is frequently initiated through imaging techniques such as ultrasound, computed tomography (CT), or magnetic resonance imaging (MRI). These scans may be undertaken to investigate kidney issues, high blood pressure causes, or for unrelated purposes.

Confirmatory Imaging: CT or MRI scans play a pivotal role in confirming the diagnosis or evaluating potential complications. The presence of ten or more cysts in each kidney is highly indicative of Polycystic Kidney Disease. This is particularly when accompanied by enlarged kidneys and cysts in other organs such as the liver. However, diagnosing the condition can be more challenging when fewer cysts are detected.

Genetic Testing: Genetic testing, while not routinely conducted due to limited availability and cost considerations, can provide a definitive diagnosis. This approach is especially valuable for individuals within a family with a history of polycystic kidney disease. It aids in the precise exclusion of the diagnosis or offers essential insights for potential kidney donors. Consequently, it prevents unforeseen complications post-donation. Genetic testing is also valuable for family planning purposes. Nevertheless, the decision to undergo genetic testing demands careful consideration due to the potential emotional and psychological impact of early diagnosis. It is important to emphasize that genetic testing entails both advantages and challenges, including potential emotional implications. Obtaining informed consent is crucial to ensure patients understand the benefits and potential drawbacks of genetic testing before proceeding.

Navigating the diagnostic pathway of Polycystic Kidney Disease necessitates a collaborative approach between patients and healthcare providers, taking into account individual circumstances and informed decision-making.

What is the Treatment of Polycystic Kidney Disease?

Addressing Polycystic Kidney Disease entails a multifaceted approach that focuses on mitigating progression, managing symptoms, and considering renal replacement therapy when required. While no cure exists due to its genetic nature, effective strategies can enhance the quality of life and potentially delay the onset of end-stage kidney disease:

Disease Progression Retardation: Slowing or minimizing the progression of the disease assumes paramount importance. A combination of measures, including medications, dietary modifications, lifestyle adjustments, and safeguarding kidney health against further insults, is imperative. Rapid disease deterioration can expedite the journey toward total kidney failure, yielding complications and potentially shortening life expectancy.

Tolvaptan is a medication which has emerged as a significant contender in reducing the size of polycystic kidneys and retarding disease progression. However, its adoption is governed by factors such as availability, cost, and potential side effects. Regular monitoring of sodium and liver enzyme levels is a prerequisite due to the medication’s side-effect profile. Patients at high risk of progression and possessing the means (or insurance coverage) should consider Tolvaptan. For those who cannot access it, maintaining ample hydration by consuming around 3-3.5 litres of water per day is advised.

Blood Pressure Control: Aggressive blood pressure management plays a central role in slowing disease progression. Target blood pressure levels for individuals with Polycystic Kidney Disease are much lower than those for patients with other chronic kidney diseases, particularly for younger individuals. Antiproteinuric medications, which also reduce blood pressure, are also prescribed due to their renoprotective effects.

Comprehensive & Holistic Management: Rigorous management of associated conditions and comorbidities is pivotal in safeguarding kidney function and overall health. Ensuring other health issues are well-controlled minimizes additional stress on the kidneys.

Renal Replacement Therapy: For those who reach end-stage kidney disease, kidney transplantation stands as the preferred mode of therapy. However, if transplantation is not feasible, hemodialysis is prioritized over peritoneal dialysis. This is due to the potential space constraints posed by enlarged kidneys in the abdominal cavity.

Ongoing Research: Research endeavours in genetic therapy offer a glimpse of hope. Ongoing studies are exploring potential breakthroughs in treatment strategies.

Psychosocial Support: Living with a chronic condition like Polycystic Kidney Disease can have emotional and psychological implications. Exploring resources for psychosocial support, coping strategies, and maintaining a positive outlook is pivotal for better physical and mental well-being, despite the disease. Psychologists and medical social workers are professionals able to provide a listening ear and moral support. There are also certain patient advocacy organizations and support groups dedicated to polycystic kidney disease. These platforms can provide valuable resources, community connections, and a space for sharing experiences and insights.

Empowering patients with knowledge about disease management, facilitating early intervention, and promoting collaboration between healthcare providers and individuals with Polycystic Kidney Disease play a pivotal role in optimizing outcomes and enhancing the patient’s journey.

When Do the Kidneys Need to Be Removed in Polycystic Kidney Disease?

The decision to remove polycystic kidneys arises in specific circumstances, driven by considerations of patient well-being and optimal medical management. Kidney removal, or nephrectomy, becomes necessary under the following circumstances:

Size-Related Constraints: Enlarged polycystic kidneys can reach proportions that significantly encroach upon the abdominal space, causing discomfort and impairing the normal functioning of other organs. In preparation for kidney transplantation, creating adequate space becomes essential, motivating kidney removal.

Complications: Severe complications, such as persistent or recurrent bleeding, severe and refractory infections, or the formation of abdominal hernias due to the enlarged kidneys’ pressure, can necessitate kidney removal. These complications can compromise both kidney function and overall health.

Suspected Renal Cancer: While rare, the unique anatomical distortions in polycystic kidneys can make early detection of renal cancer challenging. If suspicion arises or doctors confirm malignancy, cancer management may warrant kidney removal.

The decision to remove polycystic kidneys is a complex one. It requires a thorough assessment of risks, benefits, and the patient’s overall medical condition. Close collaboration between healthcare providers and patients is crucial. It helps in determining the optimal course of action, ensuring the best possible outcomes and quality of life for individuals with polycystic kidney disease.

Share via

Also worth reading

People also read:

Dr Sandy Ng Periodontal Disease
Periodontal Disease: The Silent Scourge of Oral Health

Periodontal disease, commonly known as gum disease, is a pervasive but often overlooked health issue. This oral condition affects the gums and the bones that support your teeth, and if left untreated, can lead to tooth loss and increased risks for other health problems. This article dives further into this condition, with advice from Dr Sandy Ng, General Dentist at Q&M Dental City Square Mall.

Read More »
World Toothache Day 2023
Toothache Day 2023

Did you know that teeth can’t regenerate and that it is the only part of the human body that can’t heal itself? Read more

Read More »