ADPKD is a commonly seen disorder that is observed in about 1 in 1000 live births. Almost 78 % of families with ADPKD express an abnormal Chr 16 (PKD1
Autosomal dominant polycystic kidney disease (ADPKD).
Abbreviations:
o ADPKD: Autosomal dominant polycystic kidney disease.
o Chr: Chromosome.
o CT: computed tomography.
o Dgx: Diagnosis.
o ESKD: end-stage kidney disease.
o FH: family history.
o HT: Hypertension.
o IVC: inferior vena cava.
o MRI: magnetic resonance imaging.
o Pn: Pyelonephritis.
o Sms: Symptoms.
o T/E: Thromboembolism.
o USS: Ultrasound scanning.
o UTI: urinary tract infection.
ADPKD is a commonly seen disorder that is observed in about 1 in 1000 live births. Almost 78 % of families with ADPKD express an abnormal Chr 16 (PKD1 locus). Rest of the remaining families (14 %) mostly showing a different defect involving a gene on Chr 4 (the PKD2 locus), while a minority of families expressing a defect in the GANAB gene, that encodes the glucosidase IIa subunit, or the DNAJB11 gene.
Ptns with PKD2 have a less severe phenotype than that observed in PKD1, however, neither subtypes considered benign. The reported risk factors for progressive kidney disease in ADPKD may include:
o Male sex,
o Renal size,
o Proteinuria,
o Associated HT,
o Earlier onset of Sms in age,
o High urinary Na+ excretion, &
o The culprit gene mutation within FH,
Ptns with ADPKD could be asymptomatic or seen with HT, haematuria, proteinuria, or renal dysfunction that accidentally detected by routine lab testing. Flank loin pain due to: [cystic hemorrhage, stones, or UTI] are the most commonly seen Sms reported by ptns. Ptns can be also presenting with Sms that could be attributed to cyst formation in other systemic organs, e.g., the liver, pancreas, spleen, etc...
Dgx is mostly made during routine clinical evaluation in a symptomless ptn with a +ve FH of ADPKD, working-up for a newly diagnosed HT, as accidental finding during image testing done for an unrelated problem (e.g., pregnancy, trauma, etc), and during assessment of ADPKD-related Sms (haematuria, cyst rupture, Pn, kidney stones, etc). Confirmatory diagnosis of ADPKD is mainly by imaging. On the other hand, genetic testing is usually reserved for atypical conditions or to exclude ADPKD in a young aged potential kidney donor:
1) Ptns with FH of ADPKD, with no Sms and with normal kidney function, an USS is usually adequate to diagnose or exclude the presence of ADPKD. In these subjects, MRI may be mandated if the results of the USS testing are not certain or equivocal or to further evaluation of an incidentally expected complications (e.g., kidney neoplasm or complex cyst). Some experts may proceed to genetic testing to assure the Dgx, if considered, as an alternate tool to follow-up testing with an MRI.
2) Ptns with a FH & typical finding of ADPKD, e.g., ptns with palpable kidney and lowered eGFR > obtain a CT or MRI instead of an initial USS. The preferability between CT or MRI rely primarily upon the ptn's renal function, considering the harm of contrast exposure with CT. Those with eGFR ≥60 mL/min/1.73 m2, we can consider CT without and with dye. Ptns with an eGFR <60 mL/min/1.73 m2, we prefer MRI.
3) There’re no settled imaging-based criteria for Dgx of ADPKD in ptns with absent FH. We can consider ADPKD Dgx if they have 10 or more cysts (≥5 mm) in each kidney, especially if the kidneys are enlarged in size or liver cysts are noted, and clear features of a different cystic disorder are currently lacking. Genetic testing should be proceeded, in ptns with equivocal imaging tests or with the need to establish an accurate Dgx (e.g., candidate for Tx or pre-natal programming).
4) Considering the available data in regard to the risk of progression, we proceed with genetic testing for Dgx among subjects related to families expressing the DNAJB11 mutation. Ptns with GANAB mutation, excluding the Dgx by image testing may be adequate based on their MILD phenotyping.
A timely diagnostic counselling by experienced clinicians is mandated for all ptns with possible ADPKD prior to diagnostic testing. Benefits versus adverse effects of diagnostic imaging, as well as genetic counselling and its impact on family planning should be all considered.
Other diseases rather than ADPKD must be recognized in the ptn with kidney cysts who is lacking a FH of the disease. The age of the ptn, a FH of other expected genetic diseases, and the finding of other manifestations help DD between other varieties.
CLINICAL MANIFESTATIONS
Substantially all subjects inheriting PKD1 or PKD2 mutations ultimately develop renal cysts that can be seen via USS testing. Age at which involved subjects show clinical manifestations, e.g., renal function decline or HT, is variable. Ptns with PKD1 usually observed with Sms at a younger age than ptns with PKD2 aberrations. Ptns with PKD1 typically show larger kidneys in size and more cystic changes than those with PKD2. Study: median age at presentation with ESKD was 54 & 74 y. for ptns with PKD1 & PKD2, resp.. However, early-onset disorder has been reported with both mutations. Ptns with ADPKD may show HT, haematuria/proteinuria syndrome, or renal function decline. Loin pain, due to renal hemorrhage, obstructive uropathy, or UTI, is the most seen Sm.
HT can be reported in most with normal renal function who’s reaching the 4th decade of age; HT is prevalent in almost 100 % among ptns with ESKD. Ptns may also present with Sms related to cysts involving other organs, e.g., liver, pancreas, spleen, or epididymis. Moreover, enlarged kidney & hepatic cysts may be compressing the IVC and, if is severe enough can induce hypotension, T/E, in addition to hepatic veins obstruction. Study: almost one 1/3rd of ptns with ADPKD can show ≥ 50 % compressed IVC as compared to controls. However, sequelae of compressed IVC, are not common but typically emerge with added risk factors (e.g., pregnancy, hypercoagulability states).
Most ADPKD deaths are related to cardiac causes. Study: ADPKD: causes of mortality include heart disorder (36 %), infectious episodes (24 %), & neurological accidents (12 %). Myocardial hypertrophy can be seen in 89 % of autopsy and coronary disease in 81 %. Neurologic deaths attributed to ruptured intracranial aneurysm (6 %) & HT-related intracerebral hemorrhage (5 %). No deaths related to renal cancer have been reported..
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