Polycystic kidney disease: PMM2 mutation causes PKD and hyperinsulinism
Nature Reviews Nephrology 13, 321 (2017). doi:10.1038/nrneph.2017.58 Author: Ellen F. Carney Researchers have identified a previously undescribed genetic disorder that presents with hyperinsulinaemic hypoglycaemia (HI) and polycystic kidney disease (PKD) in childhood (HIPKD). They report that this disease is caused by a promoter mutation in PMM2, which encodes the N-glycosylation enzyme phosphomannomutase 2.The coexistence
We report that calcium oxalate (CaOx) crystal deposition led to rapid tubule dilation, activation of PKD-associated signaling pathways, and hypertrophy in tubule segments along the affected nephrons. Blocking mTOR signaling blunted this response and inhibited efficient excretion of lodged crystals. This mechanism of “flushing out” crystals by purposefully dilating renal tubules has not to our knowledge been previously recognized. Challenging PKD rat models with CaOx crystal deposition or inducing calcium phosphate deposition by increasing dietary phosphorus intake led to increased cystogenesis and disease progr...
Autosomal dominant polycystic kidney disease (ADPKD) is mainly characterised by the development and enlargement of renal cysts that lead to end-stage renal disease (ESRD) in adult patients. Other clinical mani...
A potential treatment for polycystic kidney disease - a genetic disorder that causes the kidneys to swell with multiple cysts and can eventually lead to organ failure - has shown promising results in animal testing. A study describing the drug's development and testing appears today in Nature Communications. The study shows an approximately 50 percent reduction in kidney size in afflicted mice following treatment.
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ConclusionsIntracranial aneurysms are more frequent in patients with ADPKD, and the average age of intracranial artery rupture in patients with ADPKD is earlier than in the general population. It is necessary to consider proper evaluation and management of intracranial aneurysms when counseling ADPKD patients who will undergo kidney transplantation.
Conclusions: Mutations in PKD1 and PKD2 are the most common cause of ADPKD in Saudi patients with typical ADPKD. Abbreviations: ADPKD: Autosomal dominant polycystic kidney disease; CFTR: Cystic fibrosis transmembrane conductance regulator; EGF: Epidermal growth factor; MCIC: Mayo Clinic Imaging Classification; PKD: Polycystic kidney disease; TSC2: Tuberous sclerosis complex 2. PMID: 31488014 [PubMed - in process]
Studies on comorbidities seen with CKD reviewed here examine controlled vs uncontrolled gout, psychiatric diagnoses, and screening for intracranial aneurysm.
Nature Reviews Nephrology, Published online: 05 September 2019; doi:10.1038/s41581-019-0183-yIncreasing evidence suggests that dysregulation of cellular metabolism has a role in the pathophysiology of autosomal dominant polycystic kidney disease. Here the authors discuss the underlying pathways and review efforts to use pharmacological interventions and lifestyle modifications to slow disease progression.
Abstract Polycystic kidney disease (PKD) is one of the most common genetic kidney diseases, characterized by the formation of fluid-filled renal cysts, which eventually lead to end-stage renal disease. Despite several decades of investigation, explicit molecular and cellular mechanisms underpinning renal cyst formation have been unresolved until recently, severely hampering the development of effective therapeutic approaches. Currently, most PKD therapies have been developed for limiting disease complications, such as hypertension. Although Tolvaptan has been approved for treating PKD in few countries, the associa...
CONCLUSIONS: The study draws attention to important discrepancies between different decision algorithms for tolvaptan eligibility in ADPKD patients. PMID: 31473739 [PubMed - as supplied by publisher]