Introduction 

• There is no exemption while talking about hereditary disease in kidneys . Like every other organ ,kidneys & urinary tract have chances of being genetically impaired and run in families over generations.
• Most of them are recognised at childhood or prenatally in Ultrasound examination during stage of pregnancy
• Some may be either  Dominant or Recessive  .Some may  affect directly or indirectly ,mild to severe over kidneys 
• Apart from the role of urologist ,nephrologist ,nutritionist, an additional role of medical geneticist comes into action in order to treat the patient 

 Genetic or hereditary Kidney disease are classified as cystic and non-cystic diseases

a.Cystic hereditary Kidney disease includes

1.Autosomal dominant polycystic kidney disease/ADPKD

2.Autosomal recessive polycystic kidney disease/ARPKD

3.Tuberous Sclerosis

4.Von Hippel Lindau 

b.Non-cystic hereditary Kidney disease includes

1.Alport Syndrome /Hereditary Nephritis

2.Thin basement membrane Nephropathy

3.Fabry Disease

• Cystic hereditary Kidney Disease 

              1.Autosomal Dominant Polycystic Kidney Disease (ADPKD)

• Affects 1 in 500 people or 1 in 1000
• Almost 25% of cases are de novo (new)
• can leads to further progression to End stage renal disease at age of 50-55 in affected PKD 1 gene ,at age 70-75 in PKD 2
• The genes affected are PKD1 ,PKD2,PKD3 
• While most of the affected cases have mutations in the PKD1 gene  followed by PKD2 ,Very few of the PKD3 genes .

The renal complications are

• Hematuria (55-60%cases)
• Infections (35-50%)
• Stones due to deposits of uric acid ,calcium oxalate
• Decreases in ability to concentrate
• Progresses to ESRD 

Non-renal complications are

• Hepatic cysts more prevalent in women 
• Hernias in abdominal wall
• Seminal vesicle cysts 
• Hypertension
• Intracranial aneurysms
• Valvular prolapse or regurgitation

Treatment

• Maintaining hypertension less than 130/80 with use of ARBs or ACE inhibitors
• Hematuria -minimizing risk and avoiding trauma to back and abdomen 
• Urinary tract infection-often need to prolong it 
• Need lipophilic antibiotics such as Cipro,trimethoprim,chloramphenicol
• Stones may occur in 25% of patients usually by uric acid 

Diagnostic test 

Age                        Number Of Cysts

15-39.                   At least 3 uni or bilateral 

40-59.                  At least 2 in each kidney

60 or above         At least 4 in each kidneys 

   2.Autosomal Recessive Polycystic Kidney Disease (ARPKD)

• less common when compared with ADPKD
• malformation complex confined to both  kidneys and liver
• Ectatic dilatation of collecting ducts 
• Present at perinatal or natal stages
• Neonates have enlarged kidneys and also respiratory hypoplasia
• Hyponatremia presents in high incidence 
• Can have retarded growth irrespective of the disease 
• Hypertension is most common and present at early stages
• Progresses to chronic kidney disease during childhood only
• Kidney stones are very common 
• Other conditions such as hepatic fibrosis and portal hypertension can be a big trouble 

 3.Tuberous Sclerosis

• Autosomal dominant Cystic disease
• It usually affects 1/5000,1/10000
• The mutated gene was TSC1 and TSC2 
• the clinical features have a characteristic triad known as vogt’s triad 

                     Seizures

                     Mental retardation

                     Angiofibromas (fasical)

• Many hamartomatous type of tumors are evident
• Renal manifestations include Cysts ,Angiomyolipomata
• Other include cardiac rhabdomyoma
• Clinical diagnostic criteria are dominated by neurologic and dermatologic manifestations

Microscopic features shows 

•  Shagreen patch which is a connect tissue nevus 
• Ash spots which are hypo pigmented macules 
• Cortical tubers 

4.Von Hippel Lindau

• It is a systemic disorder including clear cell renal carcinoma 
• It is an autosomal dominant disease 
• Occurs in 1/ 36000 people
• Kidneys with varying degree of cystic burden and infections are common
• Central nervous system with hemangioblastomas in the retina, cerebellum and spine 
•   Can have  pheochromocytoma and other multiple pancreatic cysts 

(b)Non cystic hereditary Kidney Disease

5.Alport syndrome

• Affects 1/50000 to 1/10000 people 

• It is an X-linked disorder (85%)which occurs as a result of mutation in COL4A5 gene
• And can be autosomal recessive in almost 15 % and Autosomal dominant in about 5%
• Mutations in the gene encoding for alpha chains of type IV collagen 

Clinical presentation

• Usually occurs in males 
• In females the disease is mild ,if present only presents with microscopic hematuria and no progression of kidney failure or disease
• The disease progresses from glomeruli to End stage renal disease
• Nephrotic syndrome occurs in 30-40% patients
• Hearing loss or deafness
• Ocular abnormalities
• Positive family history of hematuria and kidney failure associated with deafness
• Diagnosis is confirmed through kidney or skin biopsies 

Renal manifestations

• Asymptomatic persistent microscopic Hematuria
• Episodes of hematuria,sometimes even after respiratory infection
• Men can reach young adulthood,hypertension and proteinuria,progressive chronic kidney disease
• End Stage renal disease  at age of 16-35 years in males 

Treatment

• The ideal treatment option is kidney Transplantation 

6.Thin basement membrane Nephropathy

• Also known as benign familial hematuria
• In this the basement membrane gets thinned out and associates with urinary abnormalities 
• It is an hereditary disease often caused due to mutations in alpha chains of type 4 collagen as alport syndrome
• Can presents gross or microscopic Hematuria
• Does Not cause any renal failure 

7.Fabry disease 

• It is an X – linked disorder 
• It occurs as a result of deficiency of alpha-galactosidase A enzyme

Clinical manifestations

• Nephrotic range proteinuria 
• Painful paresthesias of hands
• Premature CAD,CHF mimicking hypertrophic CMP
• Slow progression of chronic kidney disease to end stage renal disease in early 20 or 30’s of age
• Cutaneous angiokeratomas
• Corneal opacities
• Microscopic features include Zebra or myeloid bodies which get deposited as lamellated membrane structures. 

Treatment

• Includes Intravenous replacement recombinant human DNA 

8.Few other diseases includes

Juvenile nephronophthisis

• It is an autosomal recessive disease
• Is under classification of cystic disease complex characterized by diffuse Interstitial fibrosis with thick basement membrane 
• Medullary cysts are common

Nephrogenic diabetes insipidus

• It is an X linked recessive and autosomal recessive type 
• The gene affected was ADHRV2
• Clinical symptoms includes insensitivity of renal  concentrating system

Liddle’s syndrome

• It is an hereditary tubular transport disorder 
• This disease is caused by mutation of genes coding for beta and gamma subunits of sodium channels 

Gitelman syndrome

• It is also an hereditary tubular transport disorder
• Characteristics includes hypercalcemia  alkalosis associated with  hypocalcemia and hypomagnesemia
• Other diseases such as X-linked recessive nephrolithiasis, Dent’ disease and X-linked phosphatemic rickets  are hypercalciuric nephrolithiasis 

Bartter’s syndrome

• It is an Autosomal recessive characterized by mutation of gene encoding for furosemide sensitive Na-k-2C/co transporter located in Henle’s loop 

Lowe syndrome 

Diagnosis 

Certain procedures help to detect the state of kidneys and helpful to provide information for further evaluation regarding the healthy or unhealthy tissue left.

1.ultrasound 

2.CT scan

3.MRI scan 

Treatment 

The overall treatment for any kind of hereditary Kidney Disease concentrates on the prevention of further spread or progression of disease .Usually treated to the clinical signs and symptoms patient presents with

1.Cystic growth

For high or rapid risk of ADPKD  ,Tolvaptan therapy is recommended . Precautions should be taken .Use under supervision of expert 

2.Blood pressure 

As mentioned earlier before initiating the medical therapy , conventional therapies are considered .Salt or sodium restricted diet ,physical fitness,habit restrictions can bring down the blood pressure .If not under control then the medical therapies are considered . Antihypertensive drugs such as ACE inhibitors,ARBs.

3.Pain 

Sometimes cystic pain in unavoidable and need to be treated through medications which Sclerosis the cyst or through surgical removal

4.Hematuria

Blood in the urine is one of the commonest feature present in almost every disease .Consuming enough fluids based on the existed known cause can be helpful

5.Kidney failure 

Care should be take if in case there is chances of progressive Kidney failure .Sometimes procedures such as dialysis or preemptive Transplantations are best considered 

6.Aneurysms

Surgical clipping or by evaluating the cause and treating accordingly.

In Spite of being treated with the medications or surgically,emotional support is needed for patients to cope up with the condition by both the physician or family ,friends .

Frequently asked questions

1. What kind of kidney diseases are hereditary?

• The most commonest out of these are Autosomal dominant polycystic kidney disease

2.What causes genetic kidney disease?

• Abnormal genes which undergo mutations can causes any kind of genetic disease that run in families due to the passage of  mutated genes 

3.What is the only cure for Hereditary Kidney disease?

• Possibly there is no cure but can be prevented ,control few signs and symptoms based on its severity 

4.What age does Hereditary Kidney Disease start ?

• It is present at natal,perinatal stages since birth ,but symptoms are more relevant in 30 or 40 years of age 

5.What test is used for Hereditary Kidney Disease?

• Kidney gene pool is used to determine the affected gene 

6.Does the Hereditary Kidney Disease Skip ?

• Yes,in conditions of recessiveness the gene may skip,in dominant conditions there might be a chance of 50% to escape but still have a possible chance of 50% to heridate 

7. Is kidney damage hereditary?

• While some types of kidney disease may be inherited, 
• when kidney disease is found in multiple family members,then  the cause of the disease is not due to genetics.

8.How do you prevent genetic kidney disease?

Making healthy choices can improve the quality of life and they are  

1. Controlling your blood pressure

2.Controlling your blood sugar if you have diabetes. 

3.Following a low-salt, low-fat diet.

9.How fast does polycystic kidney disease 

• Rapid progression of disease  is defined as growth of total kidney volume (TKV) > 5% per year or a fall in estimated glomerular filtration rate of ≥5 mL/min/1.73 m2 per year.

10.Can a blood test detect polycystic kidney disease?

To find out if you have CKD or Hereditary disease , your doctor can do 2 major tests

1.Blood tests to check for the abnormal genes that cause the disease.

2.An imaging test, such as an ultrasound, CT, or MRI scan – Imaging tests that create pictures of the inside of the body.