- This article refers to the disease. For the science-fiction author, see Phillip K. Dick.
Polycystic kidney disease (PKD or PCKD, also known as polycystic kidney syndrome) is a cystic genetic disorder of the kidneys.[1]
It occurs in humans and other animals. PKD is characterized by the presence of multiple cysts (hence, "polycystic") in both kidneys. The cysts are numerous and are fluid-filled resulting in massive enlargement of the kidneys. The disease can also damage the liver, pancreas, and in some rare cases, the heart and brain. The two major forms of polycystic kidney disease are distinguished by their patterns of inheritance.
Types
Autosomal dominant
ADPKD is a late-onset disorder characterized by progressive cyst development and bilaterally enlarged kidneys with multiple cysts. It is a genetic disorder resulting from mutations in either the PKD-1 or PKD-2 gene. Cyst formation begins in the womb from any point along the nephron, although <5% of total nephrons are thought to be involved. As the cysts accumulate fluid, they enlarge, separate entirely from the nephron, compress the neighboring renal parenchyma, and progressively compromise renal function.
ADPKD occurs in 1:400–1:1,000 individuals worldwide and accounts for ~4% of end-stage renal disease (ESRD). Over 90% of cases are inherited as an autosomal dominant trait, with the remainder likely representing spontaneous mutations. Mutations in the PKD-1 gene on chromosome 16 (ADPKD-1) account for 85% of cases, whereas mutations in the PKD-2 gene on chromosome 4 (ADPKD-2) represent the remainder. A few families appear to have a defect at a site that is different from either of these loci. Direct mutation analysis of isolated cysts suggests there is loss of heterozygosity, whereby a somatic mutation in the normal "wild-type" allele of a small number of Renal tubule leads to unregulated Cell growth of the cells that ultimately form the cyst lining.
Clinical features
Presenting symptoms and signs include abdominal discomfort, hematuria, urinary tract infection, incidental discovery of hypertension, abdominal mass, elevated serum creatinine, or cystic kidneys on imaging studies, patients usually have renal pain, and develop renal insufficiency.
Approximately 50% of patients with ADPKD have end-stage renal disease (ESRD) by the age of 60, but those with ADPKD-2 tend to have later onset and slower progression. Hypertension is common and often precedes renal dysfunction. Abdominal pain and early satiety and gastroesophageal reflux symptoms are common due to the mass effect of the enlarged kidneys. Cyst rupture or hemorrhage into a cyst may produce acute pain or symptoms and signs of localized peritonitis. Hematuria may result from cyst rupture into the collecting system or from uric acid or calcium oxalate kidney stones. Nephrolithiasis occurs in about 20% of patients.
Urinary tract infection occurs with increased frequency in ADPKD. Infection in a kidney or liver cyst is a particularly serious complication. It is most often due to Gram-negative bacteria and presents with pain, fever, and chills. Blood cultures are frequently positive, but urine culture may be negative because infected kidney cysts do not communicate directly with the collecting system. Distinguishing between infection and cyst hemorrhage is often a challenge, and the diagnosis relies mainly on clinical and bacteriological findings. Radiological and nuclear imaging studies are generally not helpful.
Risk factors for progressive kidney disease include younger age at diagnosis, black race, male gender, presence of polycystin-1 mutation, and hypertension.
Numerous extrarenal manifestations of ADPKD highlight the systemic nature of the disease and likely reflect a generalized abnormality in collagen and extracellular matrix. Patients with ADPKD have a risk of cerebral hemorrhage from a ruptured intracranial aneurysm as compared to the general population. Saccular aneurysms of the anterior cerebral circulation may be detected in up to 10% of asymptomatic patients on MRA screening, but most are small, have a low risk of spontaneous rupture, and do not merit the risk of intervention. In general, hemorrhage tends to occur before the age of 50 years, in patients with a family history of intracranial hemorrhage, those who have survived a previous bleed, have aneurysms larger than 10 mm and have uncontrolled hypertension. Other vascular abnormalities include aortic root and annulus dilatation.Cardiac valvular abnormalities occur in 25% of patients, most commonly mitral valve prolapse and aortic regurgitation. Although most valvular lesions are asymptomatic, some may progress over time and warrant valve replacement. Abdominal hernia and inguinal hernia also occur with a higher frequency than in the general population.
Diagnosis
The sensitivity of renal ultrasonography for the detection of ADPKD is 100% for subjects 30 years or older with a positive family history. Diagnostic criteria require two or more cysts in one kidney and at least one cyst in the contralateral kidney in young subjects, but four or more in subjects older than 60 years because of the increased frequency of benign simple cysts. Most often, the diagnosis is made from a positive family history and imaging studies showing large kidneys with multiple bilateral cysts and possibly liver cysts. Before the age of 30 years, CT scan or T2-weighted MRI is more sensitive for detecting presymptomatic disease because the sensitivity of ultrasound falls to 95% for ADPKD type 1 and <70% for ADPKD type 2.Genetic counseling is essential for those being screened. It is recommended that screening for asymptomatic intracranial aneurysms should be restricted to patients with a personal or family history of intracranial hemorrhage. Intervention should be limited to aneurysms larger than 10 mm. Someone with this disease has a 5% chance of getting brain aneurysms.
Treatment
At present, treatment is largely supportive, as there is no single therapy that has been shown to prevent the decline in kidney function. Hypertension control with a target blood pressure of 130/85 or less is recommended.Lower levels have been reported to slow the rate of loss of kidney function. A multidrug approach that includes agents to inhibit the renin-angiotensin system is frequently required. There is no compelling evidence to recommend a low-protein diet, especially in patients with advanced kidney dysfunction where optimizing nutritional status is important. Lipid-soluble antimicrobials, such as trimethoprim-sulfamethoxazole and quinolone antibiotics that have good tissue permeation, are the preferred therapy for infected kidney cysts. Pain management occasionally requires cyst drainage by percutaneous aspiration, sclerotherapy with alcohol or, rarely, surgical drainage. Patients with ADPKD appear to have a survival advantage on either peritoneal or hemodialysis compared to patients with other causes of ESRD. Those undergoing kidney transplantation may require bilateral nephrectomy if the kidneys are massively enlarged or have been the site of infected cysts. Posttransplantation survival rates are similar to those of patients with other causes of kidney failure, but patients remain at risk for the extrarenal complications of ADPKD.
Autosomal Recessive
Autosomal recessive polycystic kidney
In cats
Polycystic Kidney Disease (PKD) is also prevalent in Persian, Himalayan, and Exotic Cats.
There are 3 possible genotypes for PKD:
- 1) N/N (2 copies of the normal allele)
- 2) N/P Heterozygote (1 normal copy and 1 copy of the PKD mutation)
- 3) P/P (2 copies of the PKD mutation)
PKD DNA testing is available to identify these genotypes to help cat breeders make more informed decisions about mating patterns.
Potential alternative treatment
There is no cure for the disease[citation needed]. The option of a transplant generally only arises after the patient reaches End stage renal disease. The researches have shown that the disease could be treated with novel tyrosine kinase inhibitors, such as anthocyanin rich foods of berries and grapes [2], [3], [4]. Moreover, soy milk, or soy yogurt (fermented soy protein), could be of supplementary functions.
References
- ^ polycystic kidney disease at Dorland's Medical Dictionary
- ^ Sweeney, William E. et al. (2000). "Treatment of polycystic kidney disease with a novel tyrosine kinase inhibitor". Kidney International 57: 33 – 40. doi:10.1046/j.1523-1755.2000.00829.x.
- ^ Teller, Nicole et al. (2009). "Suppression of the Kinase Activity of Receptor Tyrosine Kinases by Anthocyanin-Rich Mixtures Extracted from Bilberries and Grapes". Journal of Agricultural Food and Chemistry 57 (8): 3094 – 3101. doi:10.1021/jf803094a.
- ^ Lipson, Steven M. et al. (2007). "Cranberry cocktail juice, cranberry concentrates, and proanthocyanidins reduce reovirus infectivity titers in African green monkey kidney epithelial cell cultures". Molecular Nutrition & Food Research 51 (6): 752 - 758. doi:10.1002/mnfr.200600276.
