Alport syndrome (AS) is the most common genetic glomerular disease caused by mutations that affect type IV collagen. However, the clinical characteristics and significance of AS with kidney cysts are ...not well defined. This study investigated the prevalence and clinical significance of cystic kidney phenotype in AS.
Retrospective cohort study.
One hundred-eight patients with AS and a comparison cohort of 79 patients with IgA nephropathy (IgAN). Clinical, genetic, and imaging data were collected from medical records.
Cystic kidney phenotype evaluated by ultrasonography and defined as the presence of≥3 cysts in each kidney; demographic characteristics and estimated glomerular filtration rate (eGFR) at disease onset.
Cystic kidney phenotype in the AS and IgAN cohorts; time to chronic kidney disease (CKD) stage 3b and longitudinal changes in eGFR in the AS cohort.
Logistic regression analysis to test independent strengths of associations of clinical/demographic features with the binary outcome of cystic phenotype. Survival analysis for the outcome of reaching CKD stage 3b and linear mixed models for changes in eGFR over time in the AS cohort.
We studied 108 patients with AS; 76 (70%) had a genetic diagnosis. Autosomal dominant AS was prevalent, accounting for 68% of patients with a genetic diagnosis. Cystic kidney phenotype was observed in 38% of patients with AS and was associated with normal-sized kidneys in all but 3 patients, who showed increased total kidney volume, mimicking autosomal dominant polycystic kidney disease. The prevalence of cystic kidney phenotype was significantly higher in patients with AS when compared with the group of patients with IgAN (42% vs 19%; P=0.002). Patients with the cystic kidney phenotype were older and had more marked reduction in eGFR than patients without cystic changes. Among patients with AS, the cystic phenotype was associated with older age and a faster decline eGFR.
Retrospective, single-center study.
Cystic kidney phenotype is a common finding in AS. The cystic kidney phenotype is a common finding in AS, suggesting a possible role in cystogenesis for the genetic variants that cause this disease.
Hematuria is the classic renal presentation of Alport syndrome (AS), a hereditary glomerulopathy caused by pathogenic variants of the COL4A3-5 genes. An atypical kidney cystic phenotype has been rarely reported in individuals with these variants. To determine the prevalence of kidney cysts, we performed abdominal ultrasonography in a large group of patients with AS and a comparison group of patients with another glomerular kidney disease, IgA nephropathy (IgAN). Multiple kidney cysts, usually with normal kidney volume, were found in 38% of patients with AS. A few patients’ kidney volumes were large enough to mimic a different hereditary cystic kidney disease, autosomal dominant polycystic kidney disease. The overall prevalence of kidney cysts in AS was more than double that observed in the well-matched comparison group with IgAN. These findings emphasize the high prevalence of cystic kidney phenotype in AS, suggesting a likely association between the genetic variants that cause this disease and the development of kidney cysts.
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Simple kidney cysts, which are common and usually considered of limited clinical relevance, are associated with older age and lower glomerular filtration rate (GFR), but little has been known of ...their association with progressive chronic kidney disease (CKD).
Observational cohort study.
Patients with presurgical computed tomography or magnetic resonance imaging who underwent a radical nephrectomy for a tumor; we reviewed the retained kidney images to characterize parenchymal cysts at least 5mm in diameter according to size and location.
Parenchymal cysts at least 5mm in diameter in the retained kidney. Cyst characteristics were correlated with microstructural findings on kidney histology.
Progressive CKD defined by dialysis, kidney transplantation, a sustained≥40% decline in eGFR for at least 3 months, or an eGFR<10mL/min/1.73m2 that was at least 5mL/min/1.73m2 below the postnephrectomy baseline for at least 3 months.
Cox models assessed the risk of progressive CKD. Models adjusted for baseline age, sex, body mass index, hypertension, diabetes, eGFR, proteinuria, and tumor volume. Nonparametric Spearman’s correlations were used to examine the association of the number and size of the cysts with clinical characteristics, kidney function, and kidney volumes.
There were 1,195 patients with 50 progressive CKD events over a median 4.4 years of follow-up evaluation. On baseline imaging, 38% had at least 1 cyst, 34% had at least 1 cortical cyst, and 8.7% had at least 1 medullary cyst. A higher number of cysts was associated with progressive CKD and was modestly correlated with larger nephrons and more nephrosclerosis on kidney histology. The number of medullary cysts was more strongly associated with progressive CKD than the number of cortical cysts.
Patients who undergo a radical nephrectomy may differ from the general population. A radical nephrectomy may accelerate the risk of progressive CKD. Genetic testing was not performed.
Cysts in the kidney, particularly the medulla, should be further examined as a potentially useful imaging biomarker of progressive CKD beyond the current clinical evaluation of kidney function and common CKD risk factors.
Kidney cysts are common and often are considered of limited clinical relevance despite being associated with lower glomerular filtration rate. We studied a large cohort of patients who had a kidney removed due to a tumor to determine whether cysts in the retained kidney were associated with kidney health in the future. We found that more cysts in the kidney and, in particular, cysts in the deepest tissue of the kidney (the medulla) were associated with progressive kidney disease, including kidney failure where dialysis or a kidney transplantation is needed. Patients with cysts in the kidney medulla may benefit from closer monitoring.
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Background. According to foreign and domestic authors, a kidney cyst is one of the most common urological diseases and accounts for up to 2050%.
Aim. To evaluate the results of various methods of ...surgical treatment of patients with kidney cysts.
Materials and methods. An analysis was made of 124 case histories of patients who underwent inpatient treatment for symptomatic kidney cysts at the urology department of the Regional Clinical Hospital for the period 2016 to 2019. Also, an analysis of 50 case histories of patients who were hospitalized with the same diagnosis on the basis of the urological department of the emergency hospital for the same period.
Results. Puncture methods of treatment were used only in patients whose cysts radiologically corresponded to categories I and II according to Bosniak. On the basis of the urological department of the emergency hospital, 50 people were operated on in this way, of which 22 (44%) women and 28 (56%) men. The mean age of the patients was 58.25 years. Punctures of cysts with evacuation of contents without sclerotherapy 3 (6%) cases, and puncture of cysts with sclerotherapy with 96% ethyl alcohol 47 (94%) cases. The average age of patients who underwent surgery in the regional hospital was 56.612 years. According to MSCT, cysts of category I according to Bosniak were diagnosed in 96 patients (77.4%), category II in 11 (8.9%), category IIF in 11 patients (8.9%), category III in 6 (4.8%). Laparoscopic excision of the cyst wall was performed in most cases 109 (88%), laparoscopic nephrectomy was performed in 1 case (0.8%), laparoscopic nephrectomy in 10 (8%) cases, retroperitoneoscopic excision of the cyst wall 1 (0.8%), open intervention by lumbotomy access 3 (2.4%), of which nephrectomy was performed in two patients, one patient underwent kidney resection.
Conclusion. Surgical treatment of symptomatic kidney cysts was justified and necessary, as evidenced by the relief of symptoms and verification of cysts suspicious in terms of the likelihood of oncological pathology. Puncture methods of drainage and sclerotherapy are less radical, but justified in patients with high surgical risk. Excision of a cyst or resection of a kidney by laparoscopic access is an effective method of treatment that meets modern safety requirements for treatment.
Hepatocyte nuclear factor-1β (HNF-1β) is a DNA-binding transcription factor that is essential for normal kidney development. Mutations of HNF1B in humans produce cystic kidney diseases, including ...renal cysts and diabetes, multicystic dysplastic kidneys, glomerulocystic kidney disease, and autosomal dominant tubulointerstitial kidney disease. Expression of HNF1B is reduced in cystic kidneys from humans with ADPKD, and HNF1B has been identified as a modifier gene in PKD. Genome-wide analysis of chromatin binding has revealed that HNF-1β directly regulates the expression of known PKD genes, such as PKHD1 and PKD2, as well as genes involved in PKD pathogenesis, including cAMP-dependent signaling, renal fibrosis, and Wnt signaling. In addition, a role of HNF-1β in regulating the expression of noncoding RNAs (microRNAs and long noncoding RNAs) has been identified. These findings indicate that HNF-1β regulates a transcriptional and post-transcriptional network that plays a central role in renal cystogenesis.
•HNF-1β is a transcription factor that regulates branching morphogenesis and nephrogenesis in the developing kidney.•Mutations of HNF-1β in humans produce cystic kidney diseases.•HNF-1β governs the transcription and posttranscriptional regulation of cystic disease genes.
Tuberous Sclerosis Complex (TSC) is an autosomal dominant genetic disease caused by mutations in either
or
genes. Approximately, two million individuals suffer from this disorder worldwide. TSC1 and ...TSC2 code for the proteins harmartin and tuberin, respectively, which form a complex that regulates the mechanistic target of rapamycin complex 1 (mTORC1) and prevents uncontrollable cell growth. In the kidney, TSC presents with the enlargement of benign tumors (angiomyolipomas) and cysts whose presence eventually causes kidney failure. The factors promoting cyst formation and tumor growth in TSC are poorly understood. Recent studies on kidney cysts in various mouse models of TSC, including mice with principal cell- or pericyte-specific inactivation of TSC1 or TSC2, have identified a unique cystogenic mechanism. These studies demonstrate the development of numerous cortical cysts that are predominantly comprised of hyperproliferating A-intercalated (A-IC) cells that express both TSC1 and TSC2. An analogous cellular phenotype in cystic epithelium is observed in both humans with TSC and in TSC2
mice, confirming a similar kidney cystogenesis mechanism in TSC. This cellular phenotype profoundly contrasts with kidney cysts found in Autosomal Dominant Polycystic Kidney Disease (ADPKD), which do not show any notable evidence of A-IC cells participating in the cyst lining or expansion. RNA sequencing (RNA-Seq) and confirmatory expression studies demonstrate robust expression of Forkhead Box I1 (FOXI1) transcription factor and its downstream targets, including apical H
-ATPase and cytoplasmic carbonic anhydrase 2 (CAII), in the cyst epithelia of
(or
) knockout (KO) mice, but not in Polycystic Kidney Disease (
) mutant mice. Deletion of FOXI1, which is vital to H
-ATPase expression and intercalated (IC) cell viability, completely inhibited mTORC1 activation and abrogated the cyst burden in the kidneys of
KO mice. These results unequivocally demonstrate the critical role that FOXI1 and A-IC cells, along with H
-ATPase, play in TSC kidney cystogenesis. This review article will discuss the latest research into the causes of kidney cystogenesis in TSC with a focus on possible therapeutic options for this devastating disease.
Polycystic kidney disease is typified by cysts in the kidney and extra-renal manifestations including hypertension and heart failure. The main genetic underpinning this disease are loss-of function ...mutations to the two polycystin proteins, polycystin 1 and polycystin 2. Molecularly, the disease is characterized by changes in multiple signaling pathways including down regulation of calcium signaling, which, in part, is contributed by the calcium permeant properties of polycystin 2. These signaling pathways enable the cystic cells to survive and avoid cell death. This review focuses on the studies that have emerged in the past 5 years describing how the structural insights gained from PC-1 and PC-2 inform the calcium dependent molecular pathways of autophagy and the unfolded protein response that are regulated by the polycystin proteins and how it leads to cell survival and/or cell death.
•Polycystin 2 functions as a calcium permeant ion channel in ciliary plasma membrane and endoplasmic reticulum but its conductivity for cations may be location specific.•The unfolded protein release pathway and endoplasmic reticulum stress pathways are emerging ways in which polycystins can contribute to cell survival.•Polycystin proteins are novel interactors and regulators of organelle specific and macro-autophagic pathways.
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Kidney disease is a global health burden with high morbidity and mortality. Causes of kidney disease are numerous, extending from common disease groups like diabetes and arterial hypertension to rare ...conditions including inherited metabolic diseases (IMDs). Given its unique anatomy and function, the kidney is a target organ in about 10% of known IMDs, emphasizing the relevant contribution of IMDs to kidney disease. The pattern of injury affects all segments of the nephron including glomerular disease, proximal and distal tubular damage, kidney cyst formation, built-up of nephrocalcinosis and stones as well as severe malformations. We revised and updated the list of known metabolic etiologies associated with kidney involvement and found 190 relevant IMDs. This represents the 14th of a series of educational articles providing a comprehensive and revised list of metabolic differential diagnoses according to system involvement.
Alport syndrome (AS) is a progressive hereditary kidney disease characterized by hematuria, proteinuria, and progressive kidney dysfunction accompanied by sensorineural hearing loss and ocular ...abnormalities. Pathogenic COL4A3-5 variants can result in different AS spectra. Further, kidney cysts have been reported in adults with AS. However, the relationship between kidney cysts and AS remains unclear. Here, we report 3 cases of AS in children that occurred with kidney cysts. The patient in case 1 was initially diagnosed with IgA nephropathy at the age of 8 years but later developed bilateral multiple kidney cysts at the age of 17 years, suggesting autosomal-dominant polycystic kidney disease. Whole-exome sequencing identified a pathogenic COL4A5 variant and confirmed the AS diagnosis. The patients in cases 2 and 3 had already been diagnosed with X-linked AS using kidney biopsy and genetic analysis. Initial kidney ultrasonography showed nephromegaly; however, kidney cyst formation was observed during their annual follow-up. Our study supports the association between AS and kidney cysts. Kidney cysts in adolescents with suspected AS should not discourage clinicians from testing for pathogenic COL4A3-COL4A5 variants. Early detection of kidney cysts is critical because it may indicate kidney disease progression.
Kidney cysts are the most common kidney lesion, while congenital kidney cysts are mostly found in pediatric population. Neonatal kidney cysts can develop due to fetal malformations, rare genetic ...disorders or can be acquired which is very rare. Kidney cysts may be the only isolated finding or be part of the overall phenotype. They can be asymptomatic, found by ultrasound accidentally or can manifest from mild to life-threatening symptoms. Therefore, early diagnosis is very important. Autosomal dominant polycystic kidney disease and autosomal recessive polycystic kidney disease are the most common causes of kidney cysts in the neonatal population. This review highlights the most common kidney cystic diseases during the neonatal period and a rare clinical case of HNF1B-associated disease.
Background
Sickle cell disease (SCD) and autosomal dominant polycystic kidney disease (ADPKD) are relatively common genetic conditions with considerable overlap in clinical presentation. In addition ...to similarities between the signs and symptoms in sickle cell nephropathy and ADPKD, more than half of SCD patients have kidney cysts. The co-occurrence of these two diseases has not been previously reported in the literature.
Case diagnosis/treatment
A 16-year-old Black male with SCD had bilateral kidney enlargement and multiple simple cysts on ultrasound. Although kidney cysts are significantly more common in individuals affected with SCD, genetic testing with a broad kidney gene panel was performed to explore the possible presence of another underlying genetic cause of his cysts, in addition to SCD. A dual diagnosis of SCD and ADPKD was made following the identification of two copies of the common pathogenic sickle cell
HBB
variant (c.20A > T, p.Glu7Val) and a pathogenic missense variant in
PKD1
(c.8311G > A, p.Glu2771Lys).
Conclusions
SCD and ADPKD differ in pathophysiological mechanisms and treatment regimens. As such, it will be paramount for this teenager to be closely monitored for signs of diminished kidney function and to be co-managed as he transitions to adult care to ensure proper treatment and management. Early identification of individuals with both SCD and a co-occurring condition is crucial to ensuring proper clinical management. Furthermore, identifying and reporting additional patients with SCD and ADPKD dual diagnoses will help us to understand the co-occurring disease course and optimal treatments.
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