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Primary cilia are specialized sensory organelles that protrude from the apical surface of most cell types. During the past 2 decades, they have been found to play important roles in tissue development and signal transduction, with mutations in ciliary-associated proteins resulting in a group of diseases collectively known as ciliopathies. Many of these mutations manifest as renal ciliopathies, characterized by kidney dysfunction resulting from aberrant cilia or ciliary functions. This group of overlapping and genetically heterogeneous diseases includes polycystic kidney disease, nephronophthisis, and Bardet-Biedl syndrome as the main focus of this review. Renal ciliopathies are characterized by the presence of kidney cysts that develop due to uncontrolled epithelial cell proliferation, growth, and polarity, downstream of dysregulated ciliary-dependent signaling. Due to cystic-associated kidney injury and systemic inflammation, cases result in kidney failure requiring dialysis and transplantation. Of the handful of pharmacologic treatments available, none are curative. It is important to determine the molecular mechanisms that underlie the involvement of the primary cilium in cyst initiation, expansion, and progression for the development of novel and efficacious treatments. This review updates research progress in defining key genes and molecules central to ciliogenesis and renal ciliopathies., (Copyright © 2020 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: The relevance of the cause of kidney disease to prognosis among patients with chronic kidney disease is uncertain., Study Design: Observational study., Settings & Participants: 6,245 nondialysis participants in the Study of Heart and Renal Protection (SHARP)., Predictor: Baseline cause of kidney disease was categorized into 4 groups: cystic kidney disease, diabetic nephropathy, glomerulonephritis, and other recorded diagnoses., Outcomes: End-stage renal disease (ESRD; dialysis or transplantation) and death., Results: During an average 4.7 years' follow-up, 2,080 participants progressed to ESRD, including 454 with cystic kidney disease (23% per year), 378 with glomerulonephritis (10% per year), 309 with diabetic nephropathy (12% per year), and 939 with other recorded diagnoses (8% per year). By comparison with patients with cystic kidney disease, other disease groups had substantially lower adjusted risks of ESRD (relative risks of 0.28 [95% CI, 0.24-0.32], 0.40 [95% CI, 0.34-0.47], and 0.29 [95% CI, 0.25-0.32] for glomerulonephritis, diabetic nephropathy, and other recorded diagnoses, respectively). Albuminuria and baseline estimated glomerular filtration rate were associated more weakly with risk of ESRD in patients with cystic kidney disease than the 3 other diagnostic categories (P for interaction, <0.001 and 0.01, respectively). Death before ESRD was uncommon in patients with cystic kidney disease, but was a major competing risk for participants with diabetic nephropathy, whose adjusted risk of death was 2-fold higher than that of the cystic kidney disease group (relative risk, 2.35 [95% CI, 1.73-3.18])., Limitations: Exclusion of patients with prior myocardial infarction or coronary revascularization., Conclusions: The cause of kidney disease has substantial prognostic implications. Other things being equal, patients with cystic kidney disease are at much higher risk of ESRD (and much lower risk of death before ESRD) than other patients. Patients with diabetic nephropathy are at particularly high risk of death prior to reaching ESRD., (Copyright © 2014 National Kidney Foundation, Inc. All rights reserved.)

Background: The presence of a few renal cysts is considered of little relevance in healthy adults, although acquired renal cystic disease occurs in advanced kidney failure. The objective of this study was to detail renal cystic and solid lesions and identify any association with clinical characteristics., Study Design: Clinical-pathologic correlation., Setting & Participants: Potential kidney donors undergoing a standardized evaluation at the Mayo Clinic in 2000-2008., Predictors: Age, kidney function, and chronic kidney disease risk factors., Measurements: Renal cystic and solid lesions by contrast-enhanced computed tomographic images., Outcomes: Cyst number, diameter, and location., Results: After excluding 8 with cystic disease, 7 of whom had autosomal dominant polycystic kidney disease, there were 1,948 potential kidney donors (42% men; mean age, 43 years). A cortical, medullary, or parapelvic cyst ≥5 mm was present in 12%, 14%, or 2.8%. For ages 19-49 years, 39%, 22%, 7.9%, and 1.6% had a cortical or medullary cyst ≥2, ≥5, ≥10, and ≥20 mm in diameter. For ages 50-75 years, 63%, 43%, 22%, and 7.8% had a cortical or medullary cyst ≥2, ≥5, ≥10, and ≥20 mm in diameter. The 97.5th percentile for number of cortical and medullary cysts ≥5 mm increased with age (10 for men and 4 for women in the 60- to 69-year group). After age and sex adjustment, cortical and medullary cysts ≥5 mm were associated with higher 24-hour urine albumin excretion, as well as increased body surface area, hypertension, and higher glomerular filtration rate in some analyses. Angiomyolipomas, hyperdense cysts, and enhancing masses or cysts with concerning features for malignancy occurred in 2.2%, 1.2%, and 0.6% and were associated with older age (P ≤ 0.05 for each)., Limitations: Persons with known chronic kidney disease were excluded., Conclusions: Renal cysts are common, particularly in older men, and may be a marker of early kidney injury because they associate with albuminuria, hypertension, and hyperfiltration., (Copyright © 2012 National Kidney Foundation, Inc. Published by Elsevier Inc. All rights reserved.)

This article cannot comprehensively cover the enormous strides made in defining the molecular and cellular basis of renal cystic diseases over the last decade. Therefore, it provides a brief overview and categorization of inherited, developmental, and acquired renal cystic diseases, providing a relevant, up-to-date bibliography as well as a useful list of informative Internet Web sites. Its major focus is the translational biology of polycystic kidney disease. It demonstrates how emerging molecular and cellular knowledge of the pathophysiology of particular diseases such as autosomal dominant polycystic kidney disease (ADPKD) and autosomal recessive polycystic kidney disease (ADPKD) can translate into innovative therapeutic insights.

Renal epithelial cysts are caused by hereditary or acquired etiologies of undetermined molecular mechanisms. The cysts develop within renal tubules by pathogenetic processes that involve cellular proliferation, accumulation of tubule fluid within distended cavities, and remodelling of extracellular matrix. Evidence is accumulating to support the view that renal cysts are composed of moderately dedifferentiated, immature epithelial cells that proliferate abnormally and transport solute and fluid by secretion, in contrast to the usual absorptive movement of liquid in normal renal tubules. The formation and expansion of renal cysts occurs in conjunction with alterations in the extracellular matrix, including thickening of the tubule basement membrane, infiltration of the interstitium with mononuclear inflammatory cells, and interstitial fibrosis. The pathogenetic elements of cyst formation are understood well enough that it is reasonable, and of considerable importance, to examine in animal models treatment strategies that may be hypothesized to allay the progression of cystic disease to end-stage renal failure.