Bardet-Biedl syndrome (BBS), autosomal recessive, is characterized by rod-cone(retinal) dystrophy (>90%), truncal obesity (72%), postaxial polydactyly, cognitive impairment, male hypogonadotrophic hypogonadism, complex genitourinary malformations, and renal abnormalities and mental retardation. Renal disease is a major cause of morbidity and mortality. This disease entity falls under the category of ciliopathies. The molecular genetic profile of BBS is currently being investigated after the recent identification of 14 BBS genes involved in primary cilia-linked disease. Regular ophthalmologic evaluation, monitoring of renal function and lipid profile, and screening for diabetes mellitus; annual blood pressure measurement
What are the specific renal manifestations of this genetic disease?Renal malformations and abnormal renal function leading to end stage renal disease (ESRD) can be a major cause of morbidity. Renal manifestations include renal dysplasia characterized by malformation of the renal parenchyma and nephronophthisis which often presents with anemia, polyuria, and polydipsia in late childhood. FSGS and glomerular pathology also has been reported. Detrusor instability of the bladder or perhaps even duplication of the collecting system. A recent CJASN article summarized biopsy findings of this disease. This clinical study looked at 33 patients and found that renal abnormalities, including impairment of renal function and signs of chronic interstitial nephropathy of dysplastic nature, were documented in 82% of the patients. Hypertension was found in >30% of the patients and hyperlipidemia in >60%, and almost 50% had other metabolic abnormalities. Interesting, recently in another paper in Kidney International 2011, this disease model was used to study water absorption in the kidney. A cohort of patients with BBS had a urinary concentration defect even when kidney function was near normal and in the absence of major cyst formation. Subsequent in vitro analysis showed that renal cells in which a BBS gene was knocked down were unciliated, but did not exhibit cell cycle defects. The authors state that "As the vasopressin receptor 2 is located in the primary cilium, they studied BBS-derived unciliated renal epithelial cells and found that they were unable to respond to luminal arginine vasopressin treatment and activate their luminal aquaporin 2. The ability to reabsorb water was restored by treating these unciliated renal epithelial cells with forskolin, a receptor-independent adenylate cyclase activator, showing that the intracellular machinery for water absorption was present but not activated. These findings suggest that the luminal receptor located on the primary cilium may be important for efficient transepithelial water absorption."
46% of individuals with this entity have structural renal abnormalities, including calyceal clubbing or calyceal cysts, parenchymal cysts, fetal lobulation and diffuse cortical scarring, unilateral agenesis, and renal dysplasia. Clinical, this can manifest as structural abnormalities include decreased urine-concentrating capacity, renal tubular acidosis, and hypertension, stones and urinary tract infections. Progressive renal impairment frequently occurs in BBS and can lead to end-stage renal disease (ESRD) necessitating renal transplantation in up to 10% of affected individuals.
Image source: uscnk.com
Post a Comment