ADPKD disorder clinical manifestations

1. ADPKD
CLINICAL MANIFESTATIONS

2. Renal Size
• ADPKD is a multisystem disorder.
• Renal size increases with age, and renal enlargement eventually
occurs in 100% of patients with ADPKD.
• The severity of the structural abnormality correlates with the
manifestations of ADPKD, such as pain, hematuria, hypertension, and
renal impairment.

3. Cyst Development and Growth
• Many manifestations of ADPKD are directly related to renal cyst
development and enlargement.
• CRISP has provided invaluable information to the understanding of
how the cysts develop and grow. The mean increase over 3 years was
204 mL or 5.3% per year. The rates of change of total kidney and total
cyst volumes and of right and left kidney volumes were strongly
correlated.
• Baseline TKV predicted the subsequent rate of increase in renal
volume and decline in renal function.

4. Renal Function Abnormalities
• Impaired urinary concentrating capacity is common even at early
stages of ADPKD.
• 60% of children cannot maximally concentrate their urine. Plasma
vasopressin levels are increased.
• Newer studies suggest that the urinary concentrating defect and
elevated vasopressin values may contribute to cystogenesis.
• Defective medullary trapping of ammonia and transfer to the urine
caused by the concentrating defect may contribute to the low urine
pH values, hypocitric aciduria, and predisposition to stone formation.

5. • Reduced renal blood flow is another early functional defect.
• It may be caused by the changes in intrarenal pressures,
neurohumoral or local mediators, and/or intrinsic vascular
abnormalities.
• Mild to moderate persistent proteinuria (150-1500 mg/day) may be
found in a significant number of patients in the middle to late stages
of the disease. It is an indicator of a more progressive disease.

6. Hypertension
• Hypertension (blood pressure ≥ 140 mm Hg systolic /90 mm Hg
diastolic), found in approximately 50% of 20- to 34 year-old patients
with ADPKD and normal renal function, is present in nearly 100% of
patients with ESKD.
• The association between renal size and the prevalence of
hypertension supports the hypothesis that stretching and
compression of the vascular tree by cyst expansion causes ischemia
and activation of the renin angiotensin aldosterone system (RAAS).

7. There is stronger evidence for the local activation of the intrarenal
RAAS. It includes
(1) partial reversal of the reduced renal blood flow, increased renal
vascular resistance, and increased filtration fraction by short- or long-
term administration of an ACE inhibitor,
(2) shift of immunoreactive renin from the juxtaglomerular apparatus
to the walls of the arterioles and small arteries,
(3) ectopic synthesis of renin in the epithelium of dilated tubules and
cysts,
(4) ACE-independent generation of angiotensin II by a chymase-like
enzyme

8. Pain
• Pain is the most frequent symptom (60%) reported by adult patients
with ADPKD.
• Acute pain - renal hemorrhage,
passage of stones, and
urinary tract infections.
• Vascular endothelial growth factor (VEGF) produced by the cystic
epithelium -angiogenesis,
hemorrhage into cysts, and
gross hematuria.

9. • Renal cell carcinoma (RCC) is a rare cause of pain in ADPKD.
• It may manifest at an earlier age in patients with ADPKD, and a higher
proportion of sarcomatoid, bilateral, multicentric, and metastatic
tumors.
• A solid mass on USG, speckled calcifications on CT and contrast
enhancement, and tumor thrombus and regional lymphadenopathies
on CT or MRI should raise the suspicion of a carcinoma.

10. Renal Failure
• The development of renal failure in ADPKD is highly variable. In most
patients, renal function is maintained within the normal range
because of compensatory adaptation, despite relentless growth of
cysts, until the fourth to sixth decade of life
• By the time renal function starts declining, the kidneys usually are
markedly enlarged and distorted with little recognizable parenchyma
on imaging studies. At this stage, the average rate of decline in
glomerular filtration rate (GFR) is approximately 4.4 to 5.9 mL/min/yr.

11. Risk factors for RF
1) The mutated gene (PKD1 vs. PKD2),
2) Type of mutation in PKD1 (truncating versus nontruncating),
3) Modifier genes determine to a significant extent the clinical course
of ADPKD
4) Male gender,
5) Diagnosis before the age of 30 years,
6) First episode of hematuria before age 30 years,
7) Onset of hypertension before age 35 years,
8) Hyperlipidemia,
9) low level of high-density lipoprotein cholesterol,
10)sickle cell trait

12. Hematuria and Cyst Hemorrhage
• Visible hematuria may be the initial presenting symptom and occurs
in up to 40% of patients with ADPKD over the course of the disease.
• Cyst hemorrhage is a frequent complication and produces gross
hematuria when the cyst communicates with the collecting system.
• If symptoms of hematuria or flank pain last longer than 1 week or if
the initial episode of hematuria occurs after age 50 years, neoplasm
should be excluded.

13. Urinary Tract Infection and Cyst Infection
• Urinary tract infection (UTI) is common in ADPKD
• UTI - cystitis, acute pyelonephritis, cyst infection, and perinephric
abscesses.
• women are affected more frequently than men.
• Escherichia coli, Klebsiella and Proteus species, and other
Enterobacteriaceae.
• The route of - retrograde from the bladder; therefore cystitis should
be promptly treated to prevent complicated infections.

14. • When there is fever and flank pain with suggestive diagnostic imaging
but blood and urine cultures are negative, cyst aspiration under US
or CT guidance should be undertaken to culture the organism and
inform the selection of antimicrobial therapy

15. Nephrolithiasis
• Renal stone disease occurs in about 20% of patients with ADPKD.
Most stones are composed of uric acid, calcium oxalate, or both.
• Uric acid stones are more common in ADPKD than in stone formers
without ADPKD.
• Predisposing metabolic factors include
decreased ammonia excretion,
low urinary pH, and
low urinary citrate concentration
urinary stasis

16. • Extrarenal Manifestations

17. Polycystic Liver Disease
• Most common extrarenal manifestation of ADPKD.
• In contrast to the renal phenotype, the ADPKD genotype is not
associated with the severity or growth rate of PLD in patients with
ADKPD.
• Most simple hepatic cysts are solitary, and PLD should be suspected
when four or more cysts are present in the hepatic parenchyma.
• The liver in PLD contains multiple microscopic or macroscopic cysts
that result in hepatomegaly but typically there is preservation of
normal hepatic parenchyma and liver function.

18. • Hepatic cysts are exceedingly rare in children with ADPKD.
• Their prevalence by MRI in the CRISP study was 58%, 85%, and 94%,
respectively, in participants age 15 to 24, 25 to 34, and 35 to 44 years.
• Women develop more cysts at an earlier age than men. Women who
have multiple pregnancies or who have used oral contraceptives
(OCs) or estrogen replacement therapy (ERT) in the postmenopausal
period may have worse disease.

19. • Typically, PLD is asymptomatic, but reported symptoms have become
more frequent as the life span of patients with ADPKD is prolonged
with dialysis and transplantation.
• Symptoms include dyspnea, orthopnea, early satiety
gastroesophageal reflux, mechanical low back pain, uterine prolapse,
and even rib fracture, directly by mass effect include hepatic venous
outflow obstruction, IVC compression, portal vein compression, and
bile duct compression presenting as obstructive jaundice.

20. • Congenital hepatic fibrosis, always found in association with
autosomal recessive PKD, can, rarely, coexist with ADPKD.
• Contrary to PKD, which affects members of several generations
in these families, congenital hepatic fibrosis is seen in only one
generation and is not transmitted vertically, suggesting the
importance of modifier genes.
• These patients present with manifestations of portal
hypertension, but hepatocellular function is normal.

21. Intracranial Aneurysms
• About 8% of patients with ADPKD.
• Intracranial aneurysms occur in 6% of patients with a negative family
history and 16% of those with a positive family history.
• Most are asymptomatic. Focal findings, such as cranial nerve palsy
and seizure, may result from compression of local structures by an
enlarging aneurysm .

22. • Yearly rupture rates increase with size, ranging from less than 0.5%
for aneurysms smaller than 5 mm in diameter to 4% for aneurysms
larger than 10 mm.
• The mean age at rupture in ADPKD is 39 years (vs. 51 years in the
general population), with a range of 15 to 69 years.
• Most patients have normal renal function, and up to 29% have
normal BP at rupture.

24. • Screening is not indicated for all patients with ADPKD
• Indications for screening :
F/H of intracranial aneurysm or SAH
Previous aneurysm rupture
Preparation for elective surgery with potential hemodyna-
-mic instability e.g airline pilots, significant patient
Anxiety despite adequate information about the risks

25. Other Vascular Abnormalities
• Thoracic aortic and cervicocephalic arterial dissections, coronary
artery aneurysms, and retinal artery and vein occlusions.
• Thoracic aortic dissection is seven times more common in ADPKD
than in the general population in autopsy series, but reported cases
are rare.
• Coronary aneurysms and abdominal aortic aneurysms

26. Cardiac Manifestations
• Mitral valve prolapse - 25% of patients with ADPKD by
echocardiography.
• Mitral regurgitation, tricuspid regurgitation, and tricuspid prolapse
also occur more frequently in ADPKD than in unaffected kindred.

27. • Screening echocardiography is not indicated unless a murmur is
detected on physical examination.
• Small, hemodynamically insignificant pericardial effusion can be
detected by CT scanning in up to 35% of patients with ADPKD.

28. Other Associated Conditions
• Cyst formation -pancreas, seminal vesicles, and arachnoid
membrane.
• Seminal vesicle cysts - multiple and bilateral, are found in 40% of
ADPKD compared with 2% of nonaffected males.
• Ovarian cysts are not associated with ADPKD.
• Pancreas and arachnoid membrane cysts -5% and 8% of patients,
respectively.

29. • Epididymal and prostate cysts also may occur with increased
frequency.
• Sperm abnormalities with defective motility are common in ADPKD
and rarely may be a cause of male infertility.
• Spinal meningeal diverticula
• colonic and duodenal diverticula

30. • Diverticular Disease
Colonic diverticulosis and diverticulitis are more common in patients
with ADPKD and ESKD than in those with other renal diseases.

31. Bronchiectasias
• PC1 is expressed in the motile cilia of airway epithelial cells.
Bronchiectasis occurs 3 times more frequently in patients with
ADPKD than in control individuals