Polycystic Kidney Disease
last authored:
last reviewed:
Introduction
Polycystic kidney disease can be autosomal-dominant (ADPKD), with usual adult onset, or autosomal-resessive (ARPKD), with infant or childhood onset. ARPKD is accompanied by congenital hepatic fibrosis, and is usually lethal within the first year of life due to renal failure. ADPKD affects 1/200-1/1000 and is responsible for 8-10% of chronic renal failure.
The Case of...
a simple case introducing clincial presentation and calling for a differential diagnosis to get students thinking.
Causes and Risk Factors
ADPKD is the most common heriditary renal disease, affecting 4-6 million people workdwide. At least three different genes have been implicated, including ADPKD1, which codes for polycystin-1, and ADPKD2, which codes for polycystin-2. These proteins are present in the renal tubular epithelium. Polycystin-1 is involved in intracellular phosphorylation, while polycystin-2 is a calcium channel. With ADPKD1 mutations, the small number of cysts that form suggests another mutation is also required for disease.
Smoking may contribute to cyst formation.
Pathophysiology
Macroscopically, kidneys are large and filled with clear yellow fluid-filled cysts, occasionally with hemorrhage into the cysts.
Protein mutations lead to deregulation in cell-cell or cell-matrix interactions. This leads to altered tubular epithelial growth and differentiation. Abnormal ECM, and fluid secretion leads to these epithelial lined cysts.
Cysts separate from parent tubules and accumulate fluid through cAMP-mediated salt secretion.
Extrarenal cysts can occur in the liver, pancreas, and spleen. Diverticulosis is also common.
Signs and Symptoms
Manifestations rarely occur before the age of 25.
- history
- physical exam
History
Acute abdominal flank pain along with hematuria is the most common manifestation.
Nonspecific, dull lumbar pain is frequent. Sharp, localized pain can result from cyst rupture, infection, or renal calculus.
Physical Exam
Large, palpable kidneys are often present, along with possible hepatomegaly.
Hypertension occurs in 60% of patients before renal insufficiency occurs.
Investigations
- lab investigations
- diagnostic imaging
Lab Investigations
Diagnostic Imaging
Diagnosis is made on evidence of multiple cysts throughout the parenchyma, together with renal enlargement. Ultrasound is best, though contrast CT can occasionally reveal more cystic involvement. A commercial genetic test is available, but best reserved for people with nondiagnostic imaging.
Differential Diagnosis
Treatments
Treatments are aimed at preventing complications and preserving renal function. Hypertension control is extremely important, as is early treatment of infections.
Cyst infections should be treated with TMP-SMX, chloramphenicol, or ciprofloxacin.
Bilateral nephroectomy may be required in people with large kidneys or those with frequent infections once dialysis is started, and transplantations is used to manage ESRD.
Patients and family members should be educated about inheritance and manifestations of the disease, especially as symptoms can arise later
The PKD Foundation has extensive patient resources
Consequences and Course
Urinary tract infection, pyelonephritis, and cyst infections are common, but morbidity and mortality are often the result of hypertension and attending MI or stroke.
Approximately 10% of patients have cerebral berry aneurysms, the most common cause of subarachnoid hemorrhage. 25% of patients develop mitral valve prolapse.
The natural history is variable, and end stage renal disease occurs in almost 50% of people over 60.
Poor prognostic factors include involvement of ADPKD1 gene, being male or black, hypertension, presentation at an earlier age, and gross hematuria.
Renal osteodystrophy can result from loss of vitamin D hydroxylation.
Anemia can result from loss of erythropoietin production.
Resources and References
Topic Development
authors:
reviewers:
 |