Rigi10™ Malleable Penile Prosthesis
Also Known As
ADPKD, Adult Polycystic Kidney Disease, Autosomal Dominant Polycystic Kidney Disease, PKD, ARPKD, Autosomal Recessive Polycystic Kidney Disease, Infantile Polycystic Kidney Disease, Potter Type I Polycystic Kidney Disease, Polycystic Renal Disease
Definition
Polycystic kidney disease (PKD) is a genetic disorder characterized by the development of numerous fluid-filled cysts in the kidneys, leading to progressive kidney enlargement and gradual decline in renal function.1 It exists in two primary hereditary forms: autosomal dominant polycystic kidney disease (ADPKD) and autosomal recessive polycystic kidney disease (ARPKD).2 ADPKD is more common, affecting approximately 1 in 400 to 1,000 people worldwide, while ARPKD is rarer, occurring in about 1 in 20,000 to 40,000 live births.3
ADPKD is a multisystem and progressive inherited disorder with bilateral renal cyst formation associated with kidney enlargement and extrarenal organ involvement, such as the heart, liver, pancreas, spleen, and arachnoid membranes.4 The disease is primarily caused by mutations in two genes: PKD1 (chromosome 16p13.3), accounting for approximately 85% of cases, and PKD2 (4q21), contributing to about 15% of cases.5 A small percentage (approximately 1%) of cases involve mutations in the GANAB gene, which presents with a milder kidney phenotype but more prominent liver disease.6
The pathophysiology of PKD involves abnormal function of polycystin proteins (PC1 and PC2), which are present in the primary cilia of renal epithelial cells and play crucial roles in cell proliferation, differentiation, and fluid secretion.7 These proteins regulate intracellular calcium levels and cyclic adenosine monophosphate (cAMP) signaling pathways. Dysfunction in these pathways leads to increased chloride secretion across the luminal membrane, primarily through the cystic fibrosis transmembrane conductor regulator (CFTR), resulting in fluid accumulation within cysts.8
As the disease progresses, continuous expansion of cysts compresses renal vessels, causing intrarenal ischemia and activation of the renin-angiotensin-aldosterone system, which contributes to hypertension—a common early manifestation of ADPKD.9 The cysts also trigger inflammatory responses in the surrounding renal parenchyma, promoting renal fibrosis. Progressive cyst expansion, increased systemic vascular resistance, sodium retention, and advancing renal fibrosis ultimately lead to end-stage kidney disease (ESKD) in many patients.10
Clinical manifestations typically do not appear until the third or fourth decade of life in ADPKD patients, while ARPKD often presents perinatally or in early childhood with more severe symptoms.11 Common complications include hypertension, kidney pain, urinary tract infections, kidney stones, and eventually, kidney failure requiring dialysis or transplantation.12
Clinical Context
Polycystic kidney disease (PKD) represents a significant clinical challenge in nephrology practice, with important implications for patient management, screening, and treatment.1 The clinical context of PKD encompasses diagnosis, disease monitoring, management of complications, and treatment strategies aimed at slowing disease progression and preserving kidney function.
Diagnosis of ADPKD typically occurs through imaging studies, with ultrasound being the most common initial modality due to its accessibility, safety, and cost-effectiveness.2 Diagnostic criteria are age-dependent, with younger patients (15-39 years) requiring fewer cysts for diagnosis than older individuals.3 Magnetic resonance imaging (MRI) and computed tomography (CT) provide higher sensitivity for detecting smaller cysts and are often used for more detailed evaluation or when ultrasound results are equivocal.4 Genetic testing is increasingly utilized, particularly in cases with atypical presentation, early-onset disease, or for family planning purposes.5
Disease progression monitoring is essential in PKD management, with total kidney volume (TKV) emerging as the most reliable biomarker of disease progression.6 The Mayo classification system (classes 1A, 1B, 1C, 1D, and 1E) stratifies patients from lowest to highest risk for worse disease outcomes, with the last three stages associated with higher risk for end-stage kidney disease (ESKD).7 This classification helps identify high-risk patients who would benefit from more aggressive management approaches.
Hypertension is a common early manifestation of ADPKD, often preceding significant decline in kidney function, and is associated with faster disease progression and increased cardiovascular morbidity.8 Blood pressure control is a cornerstone of ADPKD management, with a target of less than 130/80 mmHg recommended.9 Angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin receptor blockers (ARBs) are preferred antihypertensive agents due to their potential renoprotective effects beyond blood pressure control.10
Pain management is another important aspect of PKD care, as many patients experience acute or chronic pain related to cyst enlargement, infection, or kidney stones.11 Treatment approaches range from conservative measures (analgesics, tricyclic antidepressants) to interventional procedures (cyst aspiration, laparoscopic cyst fenestration) in severe cases.12
Cyst infections require prompt treatment with antibiotics that have good cyst penetration, such as fluoroquinolones, trimethoprim-sulfamethoxazole, and clindamycin.13 Persistent infections may necessitate cyst drainage or, in end-stage cases, nephrectomy.14
Nephrolithiasis occurs in approximately 20% of ADPKD patients, with uric acid stones being most common, followed by calcium oxalate stones.15 Management includes increased fluid intake, urinary alkalinization with potassium citrate (particularly for uric acid stones), and standard interventional approaches when necessary.16
Tolvaptan, a vasopressin V2 receptor antagonist, represents a significant advancement in ADPKD-specific therapy.17 Clinical trials have demonstrated its efficacy in slowing the increase in TKV and the decline in estimated glomerular filtration rate (eGFR).18 However, its use requires careful patient selection, monitoring for potential hepatotoxicity, and management of side effects such as polyuria and polydipsia.19
Lifestyle modifications are recommended for all PKD patients, including increased fluid intake (at least 3 liters daily) to suppress vasopressin and decrease cAMP production, sodium restriction (<2 grams daily), and regular physical activity.20
For patients progressing to ESKD, renal replacement therapy options include dialysis and kidney transplantation, with the latter offering superior outcomes in suitable candidates.21 Nephrectomy may be necessary in cases of massively enlarged kidneys causing significant symptoms or to create space for a transplant.22
Genetic counseling is an important component of care for PKD patients and their families, providing information about inheritance patterns, recurrence risks, and reproductive options.23 Preimplantation genetic diagnosis offers the possibility of selecting embryos without PKD mutations for couples undergoing in vitro fertilization.24