Kidney Related Signs and Symptoms of Autosomal Dominant Polycystic Kidney Disease (ADPKD)

With age, cystic renal enlargement occurs in all ADPKD patients. The severity of structural abnormality generally correlates with the renal manifestations including pain, hematuria, hypertension, and renal dysfunction. Massively enlarged kidneys can also cause compression of the neighboring organs and the inferior vena cava, leading to early satiety, dyspnea, and lower extremity edema.

Hypertension—Hypertension (HTN) occurs before the onset of renal failure in more than 80% of ADPKD patients. Although the prevalence increases with age, ADPKD is associated with an earlier onset and a signifi cantly increased incidence of HTN compared to those in the general population. The cause of HTN is multifactorial including activation of the intrarenal renin–angiotensin system, defects in nitric oxide endothelium-mediated vasorelaxation, elevated sympathetic activity, and possible defects in vascular smooth muscle cells directly associated with the PKD mutations. Early onset and/or uncontrolled HTN are signifi cant risk factors for faster renal disease progression and for mortality from cardiac complications such as left ventricular hypertrophy and coronary artery disease. Uncontrolled HTN can also worsen valvular heart disease and increase the risk of intracranial aneurysmal rupture and morbidity associated with rupture.

Pain—Episodes of acute flank pain are common. The potential etiologies are cyst hemorrhage, infection, stone, or, rarely, renal tumor. Massively enlarged kidneys can cause mechanical lower back pain. A small group of patients develops chronic flank pain without an identifiable etiology except for the enlarged kidneys. These patients are at risk for narcotic and/or analgesic dependence and medication-related complications.

Hematuria, cyst hemorrhage, and retroperitoneal hemorrhage—Gross hematuria may be the initial presenting symptom. It occurs in up to 42% of ADPKD patients and can result from cyst hemorrhage, stone, infection, or renal tumor. Most cyst hemorrhages are self-limited and resolve within 2–7 days. First episodes occurring in patients older than 50 years or episodes persisting for more than a week should be investigated to rule out neoplasm. Occasionally, hemorrhagic cysts can rupture into the retroperitoneum causing retroperitoneal bleeding. This can be severe and life threatening.

Urinary concentration defect—A urine concentration defect, often associated with mild polyuria, is the most common and earliest manifestation of ADPKD. It usually goes unnoticed and is well compensated by adequate fluid intake.

Nephrolithiasis—Nephrolithiasis occurs in approximately 20% of ADPKD patients and is five times more common than in the general population. The majority of stones are composed of uric acid and/or calcium oxalate. Uric acid stones occur more frequently in ADPKD than in non-ADPKD stone formers. Factors that may contribute to the lithogenicity are urinary stasis due to distorted renal architecture, hypocitraturia, and low urinary pH (promoting uric acid stone formation). The symptoms and signs of nephrolithiasis are similar to those of non-ADPKD stone patients.

Urinary tract or cyst infections—Whether urinary tract infections occur more frequently in ADPKD patients is unclear, but their risk of complicated infections is clearly increased. Infections include cystitis, pyelonephritis, renal cyst infection, and perinephric abscesses. They occur more frequently in females than in males. The main pathogens are Escherichia coli, Klebsiella, Proteus, and other Enterobacteriaceae. Symptoms and signs are urinary frequency and urgency for cystitis; fever, chills, nausea, vomiting, and flank pain for pyelonephritis, renal cyst infection, and perinephric abscesses.

Renal failure—ADPKD1 is associated with a 20-year earlier onset of end-stage renal failure compared to that of ADPKD2. Once the renal clearance starts to decline, it decreases linearly at a rate of approximately 5.0–6.4 mL/ minute/year. Both genetic and environmental factors play a role in renal disease progression. Among patients with ADPKD1, the location of the PKD1 mutation may influence renal outcome. The mutations located in the first half of the PKD1 gene (5' region) were shown to be associated with a slightly earlier onset of renal failure compared to the mutations located in the second half of the gene (3' region).

Additional risk factors that portend a poor renal outcome include male gender, sickle cell trait, diagnosis of ADPKD before age 30 years, first episode of gross hematuria before age 30 years, hypertension before age 35 years, hyperlipidemia, low high-density lipoprotein (HDL), and cigarette smoking.

The symptoms and signs of renal failure in ADPKD, which begin to appear when the glomerular filtration rate is reduced to <30–40 mL/minute/1.73 m2, mirror those of non-ADPKD chronic renal failure.