Comprehensive Approach to the Polycystic Kidney Disease Patient: Clinical and Therapeutic Strategies in the Management of a Multifaceted Pathology

ABSTRACT


INTRODUCTION
Polycystic kidney disease (PKD) emerges as a paradigm of complexity in the field of inherited renal diseases.This genetic disorder, characterized by the formation of renal cysts, presents exceptional phenotypic variability and a wide range of clinical manifestations that challenge the clinical and therapeutic skills of health care professionals.As we unravel the complexities of its management, there is a pressing need for a multidisciplinary approach and a comprehensive understanding of this pathology.1PKD is divided into two main forms: autosomal dominant polycystic kidney disease (ADPKD) and autosomal recessive polycystic kidney disease (ARPKD).These variants present exceptional clinical and genetic heterogeneity, with a wide diversity in symptom severity, age of onset and disease progression.From a genetic approach, mutations in the PKD1 and PKD2 genes are responsible for most cases of ADPKD, whereas ARPKD is linked to mutations in genes such as PKHD1 and DZIP1L.1 The clinical manifestations of PKD are multifaceted, ranging from chronic low back pain, arterial hypertension and hematuria to extrarenal complications such as intracranial aneurysms and polycystic liver disease.This clinical diversity drives an urgent need for accurate diagnostic strategies and highly personalized therapeutics.1 Diagnosis of PKD is based on a thorough clinical evaluation, blood and urine tests, and advanced radiological imaging studies, with emphasis on the identification of distinctive features such as bilateral and multiple renal cysts.In addition, a selective genetic approach is required in cases of uncertain diagnosis or when atypical forms are suspected.1,2The management of PKD, a mainstay of this article, encompasses a diverse spectrum of therapeutic options.From symptomatic management to pharmacologic therapy to surgical therapy, a meticulous clinical strategy is required that is tailored to the severity of the disease and the patient's individual needs.2In this comprehensive review, we will explore in detail the accurate diagnosis, emerging therapeutic options, and Corresponding Author: Montoya Torres Emmanuel management of extrarenal complications associated with PKD.We will also emphasize the importance of a multidisciplinary approach, involving nephrologists, surgeons, geneticists and other specialists, to provide comprehensive care that improves the quality of life of patients affected by this complex renal pathology.PKD, with its unique complexity, requires a thorough understanding and a treatment approach that is tailored to its phenotypic and genotypic variability.2

EPIDEMIOLOGY
Polycystic kidney disease (PKD) emerges as a highly relevant entity in the renal disease landscape, given its hereditary nature and its ability to cause a wide spectrum of clinical manifestations and potentially devastating complications.A thorough understanding of the epidemiology of PKD plays a critical role in identifying at-risk populations, stratifying disease burden, and thereby planning public health interventions and making informed clinical decisions.2,3From an epidemiological perspective, PKD is classified into two main forms: autosomal dominant polycystic kidney disease (ADPKD) and autosomal recessive polycystic kidney disease (ARPKD).ADPKD, in particular, is the most prevalent variant and affects approximately 1 in 500 to 1,000 individuals worldwide, making it a globally significant genetic pathology.ARPDD, although less common, is characterized by a more severe clinical presentation and is associated with a variable incidence across ethnic populations, with prevalence rates ranging from 1 case per 20,000 to 40,000 births.3A crucial aspect of the relevance of PKD lies in its ability to trigger a progressive deterioration of renal function, leading to chronic renal failure in a substantial proportion of those affected.In addition, PKD can manifest with various extrarenal complications, such as arterial hypertension, intracranial aneurysms, polycystic liver disease, among others, adding further complexity to the clinical picture.These complications carry a significant risk for patient morbidity and mortality and require multidisciplinary medical care for their appropriate management.3 In this context, a thorough understanding of the epidemiology of PKD translates into the early identification of individuals at risk, allowing early diagnosis and thus the implementation of therapeutic and management strategies that can delay disease progression and improve patients' quality of life.In addition, epidemiological research continues to play an essential role in identifying modifiable risk factors and evaluating the efficacy of emerging therapies, contributing to the optimization of therapeutic approaches and the reduction of the disease burden associated with PKD worldwide.3,4CLINIC Polycystic kidney disease (PKD), a genetic disorder with multisystemic implications, is characterized by phenotypic heterogeneity encompassing a wide range of clinical manifestations.In its clinical presentation, two main forms are distinguished: autosomal dominant polycystic kidney disease (ADPKD) and autosomal recessive polycystic kidney disease (ARPKD), each with its own clinical expression profile.5,6 Polycystic kidney disease (PKD), an entity of genetic origin characterized by the formation of renal cysts, is broken down into types and subtypes that encompass a diversity of clinical and genetic manifestations, requiring a comprehensive understanding for effective clinical management.In this review, the main types and subtypes of PKD are explored: Autosomal dominant polycystic kidney disease (ADPKD): Classic form of ADPKD: This variant is the most common presentation and is associated with mutations in the PKD1 (polycystin-1) and, to a lesser extent, PKD2 (polycystin-2) genes.Patients with this classic form of ADPKD often present with a wide range of symptoms, including low back pain, hematuria, hypertension and multiple renal cysts.6Late-onset PKDD: Some individuals may experience disease onset later in life, usually after the age of 40.This variant is typically associated with mutations in the PKD2 gene and may manifest with slower progression and less severe symptoms compared to the classic form.6ADPKD with Extrarenal Complications: In some cases, ADPKD is accompanied by notable extrarenal complications, such as intracranial aneurysms, polycystic liver disease, and cysts in other organs, which broadens the clinical heterogeneity and complexity of its management.7 Autosomal Recessive Polycystic Autosomal Recessive Renal Disease (ARPKD): Neonatal/Infantile form of ERPAR: This variant manifests early in life, usually in infancy, and is characterized by progressive renal failure and systemic symptoms such as arterial hypertension, polyuria and polydipsia.It is associated with mutations in the PKHD1 (hepatocyte polycystin) and DZIP1L (ciliopathy) genes.7 Juvenile form of ERPAR: Although less severe than the neonatal form, juvenile ERPAR still occurs at an early age and can lead to significant renal complications, including chronic renal failure.Its genetic basis includes mutations in the TMEM67 gene.7 Atypical Forms of ERP: Autosomal Dominant Polycystic Kidney Disease with GANAB Mutations: This rare variant is characterized by mutations in the GANAB gene and has been associated with an atypical clinical presentation of ADPKD, including hepatic and renal cysts.ERPAR-Like: Some clinical cases, although presenting clinical and radiological manifestations suggestive of ERPAR, cannot identify mutations in classical ERPAR genes, suggesting the existence of mutations in as yet uncharacterized genes.7 Corresponding Author: Montoya Torres Emmanuel Differentiation between these types and subtypes of PKD is essential for appropriate clinical decision making, including the choice of specific therapies and prognostic assessment.The genetic and phenotypic complexity of PKD underscores the need for a multidisciplinary approach encompassing nephrology, medical genetics, and other relevant specialties in the management of this complex clinical entity.7,8

DIAGNOSIS
Accurate and timely diagnosis of polycystic kidney disease (PKD) is a critical component in the effective management of this heterogeneous genetic pathology, characterized by the formation of cysts in the kidneys.To comprehensively and strategically address the diagnosis of PKD requires the implementation of a multimodality approach that incorporates detailed clinical evaluation, advanced radiological imaging tests, and, in some cases, accurate genetic analysis.8,9Clinical Evaluation and Anamnesis: The diagnostic process begins a thorough clinical history, which should include an exhaustive exploration of the family history to detect possible inheritance patterns of the disease.Patients can provide relevant information on specific symptoms, such as recurrent low back pain, hematuria, arterial hypertension or other clinical manifestations.In addition, the presence of extrarenal complications, such as intracranial aneurysms or polycystic liver disease, which may be indicative of PKD, should be inquired.9,10 Physical examination: Physical examination may reveal important findings, such as palpable masses in the renal area, arterial hypertension or signs of extrarenal involvement, contributing to diagnostic suspicion and stratification of disease severity.10Laboratory tests: Laboratory tests, such as blood and urine tests, can provide valuable complementary data.The presence of microscopic or macroscopic hematuria and the detection of alterations in serum creatinine and urea nitrogen levels indicate renal dysfunction and may be indicative of progression of PKD.10 Radiological Imaging Tests: The backbone of diagnostic confirmation of PKD lies in imaging tests, especially abdominal ultrasound, which is an initially useful tool for detecting renal cysts.However, for a more accurate and detailed assessment of cyst morphology and size, as well as for differentiation between the various forms of PKD, computed tomography (CT) and magnetic resonance imaging (MRI) are commonly resorted to.These modalities provide three-dimensional visualization, allowing identification of small cysts and evaluation of extrarenal complications.11Genetic analysis: In cases of diagnostic uncertainty or when an atypical form of PKD is suspected, genetic analysis may be considered.
Sequencing of specific genes related to PKD, such as PKD1, PKD2 or genes less common in cases of ARPD, can confirm the diagnosis and provide valuable information on prognosis and therapeutic planning.11Diagnosis of PKD is a comprehensive process that requires a thorough clinical evaluation, the use of advanced imaging tests, and sometimes genetic analysis to achieve diagnostic certainty.A meticulous, multidisciplinary approach is essential to ensure an accurate diagnosis and provide a solid basis for the subsequent therapeutic management of this complex renal disease.11

TREATMENT
The effective management of polycystic kidney disease (PKD), a heterogeneous genetic entity characterized by the formation of renal cysts, requires a sophisticated and multidisciplinary therapeutic approach encompassing various medical and pharmacological strategies.In this comprehensive review, we explore the therapeutic options available for the management of PKD, taking into account its clinical complexity and genotypic variability.12Symptomatic Management and Control of Blood Pressure: The treatment of the symptoms and complications of PKD is a central aspect of the therapeutic approach.Low back pain, a frequent manifestation, is managed by analgesics and, in some cases, interventional procedures such as cyst sclerotherapy.Arterial hypertension, which affects a significant proportion of patients, requires rigorous control to prevent progressive renal deterioration and cardiovascular complications.To this end, antihypertensive agents including angiotensin-converting enzyme inhibitors (ACE inhibitors), angiotensin II receptor blockers (ARBs), diuretics, and other antihypertensive drugs are employed.122. Management of Extrarenal Complications: Since PKD can manifest with extrarenal complications, such as intracranial aneurysms and polycystic liver disease, the therapeutic approach is broadened to include monitoring and treatment of these conditions.The coexistence of intracranial aneurysms requires careful evaluation and follow-up by a medical team specializing in neurology and neurosurgery.Polycystic liver disease is addressed with supportive measures and, in severe cases, evaluation for liver transplantation may be considered.133. Vasopressin Targeted Therapies: Vasopressin inhibitors, such as tolvaptan, have emerged as a promising pharmacological option for the treatment of PKD.These agents act by reducing the production and action of vasopressin, which decreases the formation and growth of renal cysts.However, their use is associated with side effects and requires careful monitoring, including evaluation of liver and renal function.Tolvaptan has been approved in some countries for selected patients with ERP and preserved renal function.12,13 Corresponding Author: Montoya Torres Emmanuel

Continuing Research and Emerging Therapies:
Active research in the field of PKD has spurred the development of innovative therapies, including novel vasopressin inhibitors and gene therapies aimed at correcting underlying mutations.Ongoing clinical trials are evaluating the efficacy and safety of these emerging therapies, promising new therapeutic options in the future.12,13The management of polycystic kidney disease is a clinical challenge that requires a comprehensive approach combining symptom control, management of extrarenal complications, and the use of targeted pharmacologic therapies.Vasopressin inhibitor therapy and ongoing research represent areas of particular interest in the search for more effective treatments for this complex renal disease.12,13 Surgical therapy is a crucial component of the spectrum of approaches in the management of polycystic kidney disease (PKD), a genetic condition characterized by the formation of cysts in the kidneys.Patients with PKD may require surgical interventions at various stages of the disease to address specific complications or achieve effective symptom relief.This comprehensive review focuses on the clinical aspects, techniques, and advanced considerations of surgical therapy in the context of PKD. 13

SURGICAL APPROACH
Cystic nephrectomy: Cystic nephrectomy, also known as renal cyst resection, represents a key surgical intervention in the management of PKD, particularly when renal cysts reach a significant size or generate severe symptoms, such as intractable pain or compression of adjacent structures.This technique involves the selective removal of renal cysts, preserving healthy renal tissue whenever possible.Cystic nephrectomy can be performed laparoscopically or by open surgery, depending on the location and extent of the cysts, and is performed with the goal of relieving pain, improving renal function or preventing disease progression.14 Surgery for Extrarenal Complications: PKD may be associated with extrarenal complications, such as intracranial aneurysms or polycystic liver disease.In cases of intracranial aneurysms, neurovascular surgery may be required to address the risk of cerebral hemorrhage, involving embolization procedures or clipping surgery.Severe polycystic liver disease may require evaluation for liver transplantation or interventional procedures for the management of symptomatic liver cysts.14 Renal Transplantation: For patients with advanced-stage PKD, in which renal function deteriorates significantly, renal transplantation emerges as a key therapeutic option.Renal transplantation can offer substantial improvement in quality of life and survival by replacing dysfunctional polycystic kidneys with a healthy kidney from a matched donor.However, it is critical to consider the need for additional procedures, such as cyst sclerotherapy, prior to transplantation to minimize the possibility of subsequent surgical complications.14 Surgery in Cases of Hemorrhagic or Infectious Cysts: Renal cysts in patients with PKD may become hemorrhagic or infected, which may require emergency surgery to control bleeding or drain the renal abscess.These procedures involve resection of the affected cysts and, in severe cases, may include partial removal of the kidney.14 Advanced Considerations and Multidisciplinary Approach: Importantly, the decision to perform surgical therapy in patients with PKD should be individualized and based on a thorough assessment of disease severity, extent of symptoms, and the presence of extrarenal complications.A multidisciplinary approach involving nephrologists, surgeons, radiologists, and other specialists is essential for decision making and surgical planning, with the goal of maximizing clinical outcomes and quality of life for patients with PKD. 14 CONCLUSIONS Polycystic kidney disease (PKD) is a complex and heterogeneous clinical entity that presents a significant clinical challenge in its management.Throughout this article, we have explored in detail the various facets of this genetic pathology, from its diagnosis to its treatment, and have highlighted the importance of a comprehensive and multidisciplinary approach in its management.The conclusion of this analysis highlights the need for personalized clinical care that is tailored to the phenotypic and genotypic variability of PKD.Early identification of the disease through detailed clinical history, laboratory testing, and advanced radiological imaging studies is critical for accurate diagnosis and effective management.Consideration of family history and the search for extrarenal complications, such as intracranial aneurysms or polycystic liver disease, are essential steps in this diagnostic evaluation.In terms of therapy, we have emphasized the importance of addressing the symptoms and complications of PKD in a comprehensive manner.Control of arterial hypertension, relief of low back pain, and management of extrarenal complications are critical aspects of medical care.In addition, pharmacological therapy with vasopressin inhibitors, such as tolvaptan, has established itself as a promising option in the management of PRD in selected patients, although its use requires continuous monitoring and risk-benefit assessment.Surgical therapy, including cystic nephrectomy and surgery to address specific complications, plays an important role in the management of PKD, especially in situations of symptomatic cysts, severe extrarenal complications, or significant renal impairment.Surgical decision making should be individualized and based on careful evaluation of the patient's clinical situation.Ultimately, effective management of polycystic kidney disease requires a multidisciplinary approach involving Corresponding Author: Montoya Torres Emmanuel nephrologists, surgeons, geneticists and other relevant specialists.Collaboration among these professionals is essential to provide patients with PKD with comprehensive care focused on their individual needs.In summary, PKD is a complex disease that requires a comprehensive approach from diagnosis to treatment.Ongoing research and the development of emerging therapies promise significant improvements in the management of this disease in the future.The key lies in providing patients with PKD with comprehensive and personalized medical care that addresses their medical, physical and emotional needs in their quest for a better quality of life.