Introduction:
These disorders, which might have inherited or non-inherited etiologies, can cause extrarenal symptoms in children and adults. Some of the most prevalent renal abnormalities are the renal cysts brought on by these disorders, which can range in severity from end-stage renal disease to clinically inconsequential cysts. Simple renal cysts are the most frequently acquired kidney cysts, while autosomal dominant polycystic kidney disease (ADPKD), a subtype of hepatorenal fibrocystic disease (HRFCD), is the most common genetic RCD in adults.
Clinical variables, such as patient age, symptoms, renal function, and cyst characteristics (for example- size, shape, location, and number), are commonly used to differentiate and diagnose renal cystic disease. Laboratory tests, genetic testing, and renal imaging are used in diagnostic studies. Supportive care, monitoring and treating problems, and, in certain cases, transplantation are the usual components of management.
What Is the Etiology Behind Renal Cystic Abnormalities?
RCD can be categorized as inherited or non-inherited (developmental dysplasia, de novo mutations, or systemic illnesses) and includes a variety of underlying problems. The pathophysiologic origins of RCD are now better understood because of scientific advancements. Therefore, some diseases can be classified as either ciliopathies (which include mutations affecting renal tubular cilia) or dysplasias (which include abnormalities in renal anatomy). With the exception of ADPKD, most forms of RCD have genetic etiologies and initially manifest in children or teenagers. ADPKD is the most common RCD seen in adulthood.
Mutations in the PKD1 and PKD2 genes cause ADPKD. These mutations result in dysregulated tubular epithelial adhesion, aberrant ciliary activity, cell differentiation, and dysfunctional ion channels, all contributing to active fluid release into cysts. In ADPKD, renal cysts may rupture, resulting in hematuria or infection. Patients have a 25 % chance of developing nephrolithiasis and a greater-than-normal risk of developing pyelonephritis. The development of hepatic cysts is influenced by estrogen levels, which is why women are more likely than men to acquire liver cysts. Pregnancies more than once or exposure to different estrogens can raise this probability even more. Interstitial fibrosis and vascular sclerosis could also appear. The embryologic bile ducts persist and enlarge, resulting in hepatic cysts when normal ductal plate remodeling fails.
ARPKD manifests in childhood and is caused by mutations in the PKHD1 gene. Patients who survive till adulthood have some degree of liver fibrosis, and severe cases cause perinatal death, usually from pulmonary hypoplasia. As a result of renal tubular dilatation, imaging reveals tiny cystic lesions as opposed to the massive, non-communicating cysts seen with ADPKD.
What Are Renal Cystic Abnormalities in Inherited Diseases?
Three types of polycystic kidney disease are listed below.
A common cause of adult-onset, end-stage kidney disease is ADPKD, which is brought on by mutations in the PKD1 and PKD2 genes, which encode polycystin-1 and polycystin-2, respectively. The more common mutation, PKD1, has been found in about 85% of cases. It has an incidence of 5 % to 10 % in the dialysis population and is linked to numerous extrarenal symptoms.
Hepatorenal fibrocystic abnormalities are the result of autosomal recessive polycystic kidney disease (ARPKD), a rare ciliopathy brought on by PKHD1 mutations that alters the fibrocystin-polyductin complex, a protein normally found in the basal bodies of renal tubular cells and primary cilia. Due to pulmonary hypoplasia, it has a significant perinatal mortality rate and is linked to hypertension and improper liver development.
Neonates and newborns with a family history of PKD are more likely to develop glomerulocystic kidney disease, while not all instances are linked to mutations in PKD1 or PKD2. This disorder is linked to glomerular cyst formation and enlarged Bowman's space as a result of centrosome or renal tubular primary cilia gene abnormalities. Mutations in HFN1β cause hypoplastic kidneys with abnormalities in the renal calyces and collecting systems, accounting for about 10 % of cases. Notably, HFN1β is hypothesized to control PKD2 and PKHD1 transcription.
Nephronophthisis: Nephronophthisis is an uncommon autosomal recessive disease that can strike anyone at any age, although it primarily affects children and young adults. It causes end-stage renal failure before the age of thirty. Mutations in a number of genes, including NPH1 and NPH5, produce nephronophthisis, the most common genetic cause of end-stage renal failure in the first three decades of life. The age at which ESRD onset occurs is used to characterize the variations of this illness further.
Juvenile nephronophthisis is the most prevalent variation, with an incidence rate of 9:8.3 million births. Extrarenal symptoms, such as those related to hereditary syndromes like Senior-Loken syndrome (linked to retinitis pigmentosa) or Joubert syndrome (linked to cerebellar vermis aplasia), are present in 10 % to 20 % of cases. Usually, cysts are discovered joined to the collecting tubules as opposed to separated, as in Parkinson's disease.
Autosomal Dominant Tubulointerstitial Kidney Disease (ADTKD): Recently, a set of uncommon autosomal dominant genetic illnesses known as medullary cystic kidney disease (MCKD) were reclassified because of abnormalities in numerous genes. Although this categorization is still developing, it can be distinguished by ADTDK and the particular gene mutation (for example - ADTKD-UMOD). These mutations result in misfolded proteins that cause tubular and interstitial fibrosis by way of cytotoxicity. The UMOD gene is the site of the most frequent mutation. Between the ages of 40 and 70, ADTKD gradually advances to end-stage renal disease (ESRD). Depending on the particular gene mutation, extrarenal symptoms can include diabetes, gout, or neurodevelopmental disorder. Initially, the kidneys are typically normal in size, but as the illness worsens, they may shrink.
Cysts Linked to Tumor Syndromes: Autosomal dominant gene mutations with varied penetrance cause these cysts, which include Von Hippel-Lindau disease and tuberous sclerosis.
How to Diagnose Renal Cystic Abnormalities in Inherited Diseases?
Studies on Diagnostic Imaging:
Renal ultrasound is the recommended method for assessing RCD. Patients who have substantial hypertension, recurrent UTIs, flank discomfort, or other clinical symptoms of RCD, renal cysts accidentally discovered during prenatal ultrasounds, or those who have a family history of polycystic kidney disease and are at least eighteen years old are among those who qualify for ultrasound imaging.
Other Approaches:
If results from ultrasound imaging are inconclusive, additional evaluation of RCD may be conducted using renal CT and MRI. For certain disorders, like tuberous sclerosis and simple and complex renal cysts, these modalities can provide a clearer picture of the characteristics of the cyst or the course of the disease.
Genetic Examination: Genetic testing for known mutations may be considered when diagnosing patients suspected of having hereditary etiologies of RCD.
Laboratory Research:
Laboratory investigations are carried out to evaluate renal function or detect non-renal RCD symptoms, such as liver illness.
What Are the Treatment Options for Renal Cystic Abnormalities in Inherited Diseases?
The primary focus of RCD management is supportive care, which includes treating and monitoring any side effects, including discomfort, infection, and hypertension. The majority of patients with polycystic kidney disease have hypertension, and there are numerous ways to manage this condition. Angiotensin-converting enzyme inhibitors and angiotensin receptor blockers are preferred treatments. Moreover, calcium channel blockers can keep blood pressure below 130/80 mm Hg. The majority of hypertensive patients will need more than one medication, yet effective hypertension therapy can mitigate the disease's tendency to worsen renal function.
Disease of Autosomal Dominant Polycystic Kidneys
Drinking two to three liters of water daily is recommended for ADPKD to naturally inhibit vasopressin, which can help prevent cyst formation and expansion.
Other precautions include exercising frequently, maintaining a normal weight, controlling hypertension, and limiting sodium intake to ≤2 g of salt daily.
In addition to being useful for ADPKD, tolvaptan is a vasopressin receptor antagonist at the V2 receptor that has been demonstrated to reduce the formation and development of renal cysts. Tolvaptan is the only medicine approved by the US Food and Drug Administration (FDA) for ADPKD. It blocks vasopressin signaling, which would otherwise increase intracellular cyclic adenosine monophosphate, increasing renal cysts' growth and proliferation.
A course of antibiotics that effectively penetrate cysts, such as Ciprofloxacin, Clindamycin, Sulfamethoxazole-Trimethoprim, Erythromycin, Chloramphenicol, or Tetracycline, can be used to treat cyst infections in ADPKD patients.
Disease of the Autosomal Recessive Polycystic Kidney
There is only symptomatic management for ARPKD, which includes supportive respiratory therapy for pulmonary insufficiency, dialysis or kidney transplantation for end-stage renal failure, salt restriction, anti-hypertensives for hypertension, and loop diuretics for edema. Currently, the only curative treatment for ARPKD is transplantation.
Conclusion
Clinicians in adult and pediatric nephrology should collaborate to guarantee proper continuity of care for patients with renal cystic disease who may debut as children but go on to become adults. RCD typically requires a care team with specialized knowledge (such as perinatologists, neonatologists, hepatologists, nephrologists, and geneticists) to coordinate care for the patient, especially for diseases diagnosed in very young patients.
