What is polycystic kidney?
People often diagnosed as a polycystic kidney disease may become apprehensive about their future renal function and how it affects the other family members of their own. Though this disease runs in families there is always a chance to affect fifty percent of family members only and this chance is even less if the family size is small. To alleviate the fears about the polycystic kidney disease this topic will give a clearcut understanding about the disease, current diagnostic methods and treatment options
Polycystic kidney disease is one of the common inherited i.e. runs in families , kidney disease affecting 1 in 2000 population(approx ). It is the fourth most common cause for end stage renal disease in the world . The median age for ESRD is 50 years . Providing renal replacement therpy for those who got affected is a huge financial burden to the community ( aggregating 1.2 billon euros / year in europe )
Being a autosomal domenant condition affecting possibly 50% of the children if one of the parent affected by the disease. Due to diagnostic uncertainty especially in early in disease reflects the natural history of disease of the condition with a long phase of stable renal function. Children with ADPKD shows glomerular hypertrophy , microalbuminuroia,loss of urinary concentrating ability and loss of normal diurnal blood pressure rhythm as early sub clinical manifestations.
Whom To Screen
there are two options for screening the disease
1)cascade screening where the family members are screened
2)ptients with typical symptoms like urinary tract infections , microscopic hematuria renal pain ,or kidney stones
psychological symptoms reflective of concern often ignored likerisk of inhereting the disease,uncertainty about the timing , and options of delaying ESRD
HOW TO DIAGNOSE
There are two genes responsible for this disease PKD 1 and PKD 2 in 90% of population . mutations in these genes are responsible for this condition but nearly 10% patients no mutations were detected and in these patients no family history be there. There is recent evidence for the third gene is there GANAB with mild liver involvement.
How to predict progresion
1)total kidney volume TKV assesed with serial MRI scan or CT scan and basing on the these criteria three groups of patients low, intermedialte and high risk
2) genotype and age of onset of the disease
to improve the precision of dignosis combination of imaging, genetic and clinical screening will yield good results .
ADPKD is divided into three types
Type 1 : – PKD 1 gene is located short arm of 16 chromosome
Type 2 :- PKD 2 gene is located on the long arm of the 4 chromosome
Type 3: – PKD 3 GANAB gene has been identified nearly 8-10 % cases
Hepertension is the most common feature leading to the diagnosis of ADPKD . As the size of the of the kidney increases ( Total kidney volume increases nearly 5.2% per annum ) young individual with large kidney size loose kidney funcion rapidly .Hematuria (Blood in urine ) , Abdominal pain, frequent urination due to decreased concentrating ability of the kidneys .
Extra renal involvement
Though the name involves kidney disease other organ are also involved ( Extra reanl ) like cysts in the liver , pancrease,epidydymis . Aneurysms (Dilatation of blood vessels ) in the brain is one of the improtant disease which has catastophic presentation like sudden rupture may lead to sudden death hence all patients of ADPKD suggested to undergo screening CT scan . cadiac valve defects ( ASD & Mitral valve prolapse) may present with recurrent chest pain and shortness of breath .they should go cardiac evaluation . Large intestine conditions like diverticulosis may present with severe abdominal pain and massive hemorrahge .
Other cystic conditions that mimics ADPKD
Tuberous sclrosis complex and Von-Hipple – Lindau Disease and aquired cystic disease of the kidney Mimic cystic kidney disease with malignant potential and before diagnosing ADPKD these conditions should be ruled out .
In the earlier stages strict blood pressure control and adequate water in take is useful in dalay in progress of the disease. Serial measurement of kidney volume by MRI scan is useful is assesing the kidney disease. Other drugs tried in this condition is mainly for the reduce the size of the cysts or to reduce the fibrogenesis of the kidneys
1) Tolvaptin is one drug tried in this condition to delay the cyst growth . there .are several clinical studies conducted of the efficacy of this drug but results are not so encouraging and the current practice is this drug can be advised in early stages of the kidney disease . (ERA –EDTA ) .(TEMPO3/4 Trial) . the treatment is offered to the highest risk of developing ESRD and therefore potentially the ones to benefit .It is clear that the risks and benefits of taking tolvaptin will need careful monthly monitoring of liver function tests and the profound water diuresis need excessive water intake.
2) Other drugs like somatostatin analouges , Tyrosine kinase inhibitors are currently being tested in clinical trials . combination of tolvaptin with above drugs are in preclinical trails.
3) Mammalian Traget of Rapamycin is also under clinical evaluation
4) At preasent adequate water intake is advised to reduce the progression of cysts which may be more helpful than any other medication availabe so for aart from anti hypertensives and other supportive medications.
Does it cause cancer
Cysts in autosoamal dominant poly cystic disease may grow to huge size and they are considered to be precancerous. The chances of malignancy are even higher if it is associated other syndromes like tuberous sclerosis,von-hipple lindu disease and aquired cystic diseses of the kidneys.
Cyst infections are really trouble some
Cyst infections are common in the course of ADPKD as it cause rapid worsening of the renal function. The symptoms are fever with chills and rigors, fatigue, flank pain , dysuria,hematuria and increased frequency of urine. These patients were immediately admitted in the hospital and to be evaluated . bed rest, anto biotics,anti pyretics and other supportive medication were sufficient most of the times . In severe cases these patients may need renal replacement also.
Some times patients often presents with severe pain , hematuria and passing of blood clots in the urine. This is due to massive hemorrage in the cysts and these cases can be treated with rest and conservative medication . severe cases may need removal of the affeced kidney.
Pressure symptoms are the main culprit
In this condition renal function structers are normal but ther are compressed by the slowly expanding cysts that compress the normal functioing glomeruli that is the functional tissue of the kidney and results in loss of function. The treatment modalities are directed towords the arrest of the cyst growth by various means of medication
The Mangement of ADPKD , once considered an untreatble disease, is undergoing a major paradigm shift with more accurate diagnostic, prognostic,scoring and availbility of new disease modifying drugs .This leads more attention to words the patients with the polycystic disease, in turn, treatment and patient-centered research priorities are likely to alter the long – term management of ADPKD for patients and their families.