​Kembara Xtra - Medicine - Polycystic kidney Disease

​Kembara Xtra - Medicine - Polycystic kidney Disease 
There is a category of monogenic diseases that cause the development of renal cysts. Of them, autosomal dominant polycystic kidney disease (ADPKD) and autosomal recessive polycystic kidney disease (ARPKD) are the most common.
One of the most prevalent genetic diseases in people is ADPKD.

Epidemiology: ADPKD typically manifests later in life.
- 57 to 69 years is the average age for end-stage kidney disease (ESKD) - More serious illnesses affect men than women.
Up to 90% of persons develop liver cysts.
ARPKD is typically found in newborns. A small percentage of older kids and young adults may develop liver disease. There are situations when nonobstructive intrahepatic biliary dilatation occurs.
- found in all races and on all continents.
Incidence
ESKD mean age is 54.3 years for PKD1 mutation and 74 years for PKD2 mutation. ADPKD affects 1/400 to 1,000 live births, while ARPKD affects 1/20,000 live births with a carrier level of 1/70.
Prevalence
8.7/1 million in the US as ESKD, ADPKD; 7/1 million in Europe

Pathophysiology and Etiology  

In ADPKD, mutations in the genes encoding polycystins 1 and 2 (PC1 and PC2, respectively) disrupt the function of polycystins on the primary cilium, resulting in fluid-filled cysts that progressively grow in size and cause gross kidney enlargement and distortion of the renal architecture. Glomerular hyperfiltration makes up for the gradual loss of healthy glomeruli, so by the time GFR reduction is noticed, up to half of the initial functional glomeruli have already been irrevocably gone. The ARPKD - PKHD1 product fibrocystin is also seen in cilia. The majority of ADPKD patients eventually advance to ESKD.
ADPKD: Only 1% of nephrons develop cysts: - Autosomal dominant inheritance pattern, but a molecularly recessive disease with the 2-hit hypothesis - Requires both genetic and environmental variables
ARPKD: The gene exhibits a genotype-phenotype link and several mutations.

Genetics

50% of the children of a person with ADPKD, an autosomal dominant hereditary disease, are also affected.
- Genetic imprinting and genetic anticipation are also observed, along with 100% penetrance.
- Two genes were found.
85% of patients have PKD1 on chromosome 16p13.3, which encodes polycystin 1, and 15% of patients have PKD2 on chromosome 4q21, which encodes polycystin 2.
Siblings have a 1:4 risk of developing ARPKD, an autosomal recessive disorder; the gene PKHD1 on chromosome 6p21.1-p12 encodes fibrocystin.
RISK ELEMENTS
ESKD onset at or after age 55, stage III CKD development at or after age 40, the onset of HTN at or after age 18, total kidney volume greater than expected for a given age, or the occurrence of various comorbidities (gross hematuria, microalbuminuria) all indicate a more rapidly progressive clinical course.


Prevention Genetic advice


Accompanying Conditions 

Polycystic liver disease affects 58% of young people and 94% of people over 45, according to ADPKD.  Arachnoid (8%), seminal (40%), and pancreatic (5%).
- Vascular signs and symptoms
Aortic root dilatation and dissections are found in 16% of patients with family history and 6% of patients without intracerebral aneurysms.
- Cardiac signs and symptoms
Left ventricular hypertrophy - Diverticular illness; 25% mitral valve prolapse;
Liver involvement in ARPKD is inversely correlated with renal disease and includes congenital hepatic fibrosis with portal hypertension.

Diagnosis 
ADPKD - Positive family history (15% of mutations are new).
- Backache: 60%
- Hematuria, UTI, and HTN: 50% of patients aged 20 to 34; 100% had ESKD
- Renal problems
- Presymptomatic ADPKD screening for children at risk is not yet advised.
30% of infected newborns with ARPKD pass away:
Prenatal testing identifies oligohydramnios and enlarged echogenic kidneys.
Adults and adolescents who develop portal hypertension problems, such as esophageal varices and hypersplenism, later in life.

HTN, flank masses, and clinical examination


Differential diagnosis: Tuberous sclerosis (prevalence 1/6,000), ADPKD and ARPKD, 1/36,000 cases of Von Hippel-Lindau syndrome.
10-20% of pediatric renal failure cases are due to nephronophthisis, which also causes medullary cystic kidney disease. Multicystic dysplastic kidneys, the most prevalent type of bilateral cystic disorders in infants (prevalence: 1/4000), are highly malformed kidneys. Simple cysts are the most prevalent type of cystic anomaly. They can be unilateral or localized.
Sponge kidney with a medullary layer and acquired renal cystic disease
Cystic nephromas, a benign multilocular cyst, are renal cystic neoplasms. 

Laboratory Results 
Initial Lab and Imaging Tests (Electrolytes, BUN/creatinine, Urine Analysis, and Urinary Citrate) for ADPKD - Renal Dysfunction
 Reduced renal function, hypocitraturia, and aciduria The hyperfiltration
 An increase in creatinine
- Hematuria and moderate proteinuria on urine analysis
Anemia, thrombocytopenia, and leukopenia are all symptoms of ARPKD, along with electrolyte problems and renal failure.
The simplest diagnostic approach for ADPKD in the US is not the best for excluding the condition before the age of 40.
Renal hypertrophy occurs in everyone.
 In patients at risk: Two unilateral or bilateral renal cysts are 100% diagnostic by the age of 30. It can be detected in utero and occasionally has symptoms that are similar to ARPKD in children. Hepatic cysts are pathognomonic for ADPKD in young people.
The diagnosis is made in the absence of a family history by bilateral renal hypertrophy and cysts.
Ideally, a CT scan or MRI should be included in the initial evaluation.
MRI or CT measurements of kidney capacity are important indicators of progression.
 Beneficial for locating cysts in other organs
Less than five cysts by MRI rule out the diagnosis in persons under 40.
ARPKD - US: Enlarged, uniformly hyperechogenic kidneys (cortex and medulla).
- If a diagnosis is uncertain, a CT scan is more accurate.
- The diagnosis is aided by the presence of hepatic fibrosis.


Tests in the Future & Special Considerations
Beyond age 2 years, renal size decreases in ARPKD but continues to expand in ADPKD at an average rate of 5.27% per year. Diagnosis and prevention of secondary issues caused by renal and hepatic abnormalities Follow-up of combined renal volume to determine disease severity. Patients with progressing illness are identified by their total kidney volume.

Other/Diagnostic Procedures
When imaging results are unclear in ADPKD and for potential living related donors, genetic testing for PKD1 and PKD2 is an option.
Prenatal diagnosis is possible in roughly 72% of patients with ARPKD who have PKHD1.
Interpretation of Tests
Kidneys in ADPKD are diffusely cystic, although they nonetheless maintain their overall form despite being enlarged.
- Cysts are uniformly dispersed throughout the brain and medulla and range in size from a few millimeters to several centimeters.
- Despite originally emerging from the collecting ducts, they develop in every segment of the nephron.
- The size of one kidney may differ from the other.
- The discovery of more than ten cysts per kidney by ultrasonography in patients without a known family history is typically regarded as diagnostic.
There is a continuum of ARPKD disease, from minor renal disease with significant liver damage to severe renal disease with minimal liver damage.
- Fusiform dilatation of the collecting ducts in the brain and medulla during the neonatal period causes renal hypertrophy.
- The liver lesion is widespread but only affects the fibrotic portal regions.
In severe neonatal or infantile cases, a diagnosis is most usually made based on clinical imaging and supported by enlarged echogenic kidneys, a lack of other characteristics, and a negative family history.
The gold standard for diagnosing this illness is molecular diagnostic analysis.

Management 

HTN: moderate sodium restriction, weight management, and regular exercise; medications; angiotensin receptor blockers (ARBs); pain management; opioids and other analgesics; bed rest; and a limit on NSAIDs (they decrease renal function).
Hematuria: Reduce physical activity. Urolithiasis: treated with alkalinization of urine and hydration therapy; surgery as necessary. UTIs/infections of cysts: lipid-soluble antibiotics (e.g., trimethoprim-sulfamethoxazole and chloramphenicol) are more effective.

There are currently medications and treatments that specifically target cytogenic pathways, such as lowering cAMP levels in cystic tissues. In patients with early ADPKD, tolvaptan decreased the rate of kidney development and the predicted GFR decline.
HTN should be closely managed to avoid problems. If there are no contraindications, ACE inhibitors are preferable.
Antihypertensive medication use has been shown to lower mortality.
Statins are preferred for hyperlipidemia


Referral; primary management by a nephrologist; urologic consultation for the management of symptomatic/infected cysts; and genetic counseling are all essential.

Indications for surgery include uncontrollable high blood pressure, severe back and loin discomfort, and abdominal fullness. Renal function may also deteriorate as a result of growing cysts.
- Hematuria, bleeding, or recurrent UTI
 Percutaneous cyst aspiration injection of sclerosing agent; not typically performed due to recurrent fluid accumulation Open and laparoscopic cyst unroofing: may reduce pain and narcotics requirements; has not been proven to prevent renal failure or to prolong current renal function Renal transplant for ESKD


Admission 
extreme pain, filthy hematuria, and clots

Follow-Up None in the early stages of the illness; avoid strenuous activities if the illness worsens. Trauma-related recurrent gross hematuria is linked to a quicker deterioration in renal function.
patient observation
Follow renal and blood pressure function. Encourage drinking water. actively treat stone disease and UTI.
 Steer clear of nephrotoxic medications.
 Creatinine and blood pressure checks at least twice a year; more frequently as necessary.  Intracranial aneurysm detection

Diet 

A diet low in protein may delay renal failure.
Limit your caffeine intake because it might promote cyst growth.
High water consumption to lower ADH >3 L/day (7)[C]
PROGNOSIS
 Renal failure affects 2% of people by age 40, 23% by age 50, and 48% by age 73.  10- 15% of dialysis patients have ADPKD. Renal cell cancer incidence has not increased.

Complications include the development of renal failure and cyst rupture, infection, or bleeding. kidney calculi

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