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Dominant Polycystic Kidney Disease (dominant + polycystic_kidney_disease)
Kinds of Dominant Polycystic Kidney Disease Selected AbstractsTherapeutic mTOR Inhibition in Autosomal Dominant Polycystic Kidney Disease: What Is the Appropriate Serum Level?AMERICAN JOURNAL OF TRANSPLANTATION, Issue 7 2010G. Canaud Autosomal dominant polycystic kidney disease (ADPKD) is the most common inherited renal disease, and sirolimus, a mammalian target of rapamycin (mTOR) inhibitor, has been shown to significantly retard cyst expansion in animal models. The optimal therapeutic dose of sirolimus is not yet defined. Here, we report the history of a previously unknown ADPKD deceased donor whose kidneys were engrafted in two different recipients. One of the two received an immunosuppressive regimen based on sirolimus for 5 years while the other did not. After transplantation, both patients developed severe transplant cystic disease. Donor DNA sequence identified a new hypomorphic mutation in PKD1. The rate of cyst growth was identical in the two patients regardless of the treatment. While sirolimus treatment reduced the activation of mTOR in peripheral blood mononuclear cells, it failed to prevent mTOR activation in kidney tubular cells, this could account for the inefficiency of treatment on cyst growth. Together, our results suggest that the dose of sirolimus required to inhibit mTOR varies according to the tissue. [source] Mosaicism in Autosomal Dominant Polycystic Kidney Disease Revealed by Genetic Testing to Enable Living Related Renal TransplantationAMERICAN JOURNAL OF TRANSPLANTATION, Issue 1 2008A. Connor Patients with end-stage renal disease (ESRD) secondary to autosomal dominant polycystic kidney disease (ADPKD) receive fewer living-related kidney (LRK) transplants than other groups with ESRD. This relates to the difficulties in excluding the disease in potential donors. We report a case which highlights these difficulties and, by discovery of mosaicism for a new mutation, illustrates the role of clinical and molecular genetic resources in assessing young related kidney donors for patients with ADPKD. [source] Novel method for genomic analysis of PKD1 and PKD2 mutations in autosomal dominant polycystic kidney disease,HUMAN MUTATION, Issue 2 2009Ying-Cai Tan Abstract Genetic testing of PKD1 and PKD2 is useful for diagnosis and prognosis of autosomal dominant polycystic kidney disease (ADPKD), particularly in asymptomatic individuals or those without a family history. PKD1 testing is complicated by the large transcript size, complexity of the gene region, and the extent of gene variations. A molecular assay was developed using Transgenomic's SURVEYOR Nuclease and WAVE Nucleic Acid High Sensitivity Fragment Analysis System to screen for PKD1 and PKD2 variants, followed by sequencing of variant gene segments, thereby reducing the sequencing reactions by 80%. This method was compared to complete DNA sequencing performed by a reference laboratory for 25 ADPKD patients from 22 families. The pathogenic potential of gene variations of unknown significance was examined by evolutionary comparison, effects of amino acid substitutions on protein structure, and effects of splice-site alterations. A total of 90 variations were identified, including all 82 reported by the reference laboratory (100% sensitivity). A total of 76 variations (84.4%) were in PKD1 and 14 (15.6%) in PKD2. Definite pathogenic mutations (seven nonsense, four truncation, and three splicing defects) were detected in 64% (14/22) of families. The remaining 76 variants included 26 missense, 33 silent, and 17 intronic changes. Two heterozygous nonsense mutations were incorrectly determined by the reference laboratory as homozygous. "Probably pathogenic" mutations were identified in an additional five families (overall detection rate 86%). In conclusion, the SURVEYOR nuclease method was comparable to direct sequencing for detecting ADPKD mutations, achieving high sensitivity with lower cost, providing an important tool for genetic analysis of complex genes. Hum Mutat 0, 1,10, 2008. © 2008 Wiley-Liss, Inc. [source] Retroperitoneal laparoscopic decortication of simple renal cysts using the bipolar PlasmaKinetic scissorsINTERNATIONAL JOURNAL OF UROLOGY, Issue 4 2006AHMET TEFEKLI Objectives:, To analyse the efficacy, safety and feasibility of retroperitoneal laparoscopic decortication of simple renal cysts using bipolar PlasmaKinetic scissors. Methods:, Records of 19 patients who underwent laparoscopic decortication of simple renal cysts, performed with bipolar PlasmaKinetic scissors without additional fulguration of the base or the margin of resection, were retrospectively reviewed. Long-term symptomatic and radiological outcomes were assessed. Results:, One single cyst was treated in fourteen (73.7%) cases, two cysts in three (15.8%) cases, three cysts in one (5.2%) case and multiple cysts in one case with autosomal dominant polycystic kidney disease. They were peripherally located in thirteen, peripelvic in three, and parenchymal in two cases. An average of 3.1 trochars were used for each procedure. The mean operating time was 82.5 ± 16.7 min (range, 50,135). Neither open conversion nor blood transfusion was necessary. A total of six minor complications were encountered. Mean hospital stay 2.3 ± 0.9 days (range, 1,4). After a mean follow up of 14.3 ± 5.9 months (range, 3,24), symptomatic success was achieved in 89.5%, and radiological success was accomplished in 88.2%. An asymptomatic cyst recurrence was observed in one (5.9%) case, and one (5.9%) case with residual pain had new cyst formation at another site of the kidney. Conclusions:, Retroperitoneal laparoscopic cyst decortication using bipolar PlasmaKinetic scissors is a feasible and efficient method, eliminating further fulguration of the base and the margins of the cysts. Operating times are shorter than previously published series and highly satisfactory long-term success rates are achieved. [source] Assessment of renal function with color Doppler ultrasound in autosomal dominant polycystic kidney diseaseINTERNATIONAL JOURNAL OF UROLOGY, Issue 3 2001Akira Kondo Abstract Background: Measurement of renal blood flow by color Doppler ultrasound is useful for assessment of renal function in a variety of renal disorders. In autosomal dominant polycystic kidney disease (ADPKD), however, it might be difficult to visualize interlobar arteries because of deformity of renal structure. To evaluate the usefulness of color Doppler in ADPKD, parameters determined by blood flow examination were compared with the results of ordinal renal function tests. Methods: Twenty-one patients with ADPKD were examined by color Doppler ultrasound measurement. In each patient, 10 interlobar arteries in both kidneys were investigated. Minimum blood flow velocity (Vmin), maximum blood flow velocity (Vmax), mean blood flow velocity (Vmean), acceleration, resistive index and pulsatility index were measured in relation to the results of creatinine clearance, serum creatinine, blood urea nitrogen and 15 and 120 min values of the phenolsulfonphthalein test. Results: In all patients, interlobar arteries were able to be visualized and blood-flow profile was measured. Although variations of Vmin, Vmax, Vmean and acceleration were relatively large, the resistive index and pulsatility index varied little in each kidney. Mean values of Vmin (P < 0.005), Vmean (P < 0.05), resistive index (P < 0.005) and pulsatility index (P < 0.005) were well correlated to creatinine clearance with statistical significance. Conclusions: In ADPKD, color Doppler ultrasound measurement is a useful method for assessment of renal function and could be used for monitoring the dynamic state of renal blood flow as a non-invasive technique. [source] Polycystin-2 associates with the polycystin-1 homolog, suREJ3, and localizes to the acrosomal region of sea urchin spermatozoaMOLECULAR REPRODUCTION & DEVELOPMENT, Issue 4 2004Anna T. Neill Abstract Polycystin-2, the protein mutated in type 2 autosomal dominant polycystic kidney disease, is an integral transmembrane protein with nonselective cation channel activity. Here we report on the sea urchin sperm homolog of polycystin-2 (suPC2). Like other polycystin-2 family members, suPC2 is a six-pass transmembrane protein containing C-terminal cytoplasmic EF hand and coiled-coil domains. The protein localizes exclusively to the plasma membrane over the sperm acrosomal vesicle. This localization coincides with the previously reported localization of the sea urchin PC1 homolog, suREJ3. Co-immunoprecipitation shows that suPC2 and suREJ3 are associated in the membrane. The location of suPC2 sug-gests that it may function as a cation channel mediating the sperm acrosome reaction. The low cation selectivity of PC2 channels would explain data indicating that Na+ and Ca2+ may enter sea urchin sperm through the same channel during the acrosome reaction. Mol. Reprod. Dev. 67: 472,477, 2004. © 2004 Wiley-Liss, Inc. [source] Carotid vascular remodelling in patients with autosomal dominant polycystic kidney diseaseNEPHROLOGY, Issue 1 2009SHU RONG SUMMARY Aim: To study carotid vascular wall remodelling in patients with autosomal dominant polycystic kidney disease (ADPKD) using integrated backscatter signal (IBS) analysis. Methods: Included in the study were: 60 ADPKD patients with preserved renal function, including 32 patient with hypertension and 28 with normotension; 25 patients with essential hypertension; and 30 healthy volunteers. Carotid intima-media thickness (IMT) was measured by 2-D conventional ultrasonography. Acoustic tissue characterization of the carotid wall was assessed by IBS analysis, and the percentage of regions considered as fibromatosis was calculated in all groups. Results: Carotid IMT in hypertensive ADPKD patients (0.8 ± 0.05 vs 0.68 ± 0.02 mm, P < 0.01 and 0.8 ± 0.05 vs 0.56 ± 0.04 mm, P < 0.01 respectively) and patients with essential hypertension (0.79 ± 0.03 vs 0.68 ± 0.02 mm, P < 0.01 and 0.79 ± 0.03 vs 0.56 ± 0.0 4 mm, P < 0.01 respectively) was significantly greater than that of normotensive patients and healthy subjects. Carotid IMT in normotensive ADPKD patients was also significantly greater than that in healthy subjects (0.68 ± 0.02 vs 0.56 ± 0.04 mm, P < 0.01). Calibrated IBS (C-IBS) in hypertensive ADPKD patients was significantly greater than that in patients with essential hypertension and normotensive ADPKD patients (,21.2 ± 1.51 dB vs ,23.1 ± 1.61 dB, P < 0.05; ,21.2 ± 1.51 dB vs ,24.5 ± 1.34 dB, P < 0.01). C-IBS in normotensive ADPKD patients was significantly greater than that in healthy subjects (,24.5 ± 1.34 dB vs ,26.2 ± 1.69 dB, P < 0.01). The percentage of regions that could be considered as fibromatosis in hypertensive ADPKD patients was significantly greater than that in patients with essential hypertension and normotensive ADPKD patients (30.0% vs 22.4%, P < 0.05; 30.0% vs 17.9%, P < 0.01). The percentage of regions that could be considered as fibromatosis in normotensive ADPKD patients was significantly greater than that in healthy subjects (15.2% vs 10.3%, P < 0.01). Conclusion: Carotid remodelling occurs in the early stage of ADPKD and can be aggravated by hypertension. Fibrosis contributes to the vascular rearrangement. [source] Screening for intracranial aneurysms in autosomal dominant polycystic kidney diseaseNEPHROLOGY, Issue 4 2003Review Article SUMMARY: Screening patients with autosomal dominant polycystic kidney disease (ADPKD) for asymptomatic intracranial aneurysms has been proposed as a method of reducing the morbidity and mortality associated with aneurysm rupture. However, recent studies have shown lower spontaneous rupture rates of small aneurysms and higher risks of significant complications with interventions than previously reported. Risk-benefit analysis has not demonstrated any benefit of screening ADPKD patients without a history of subarachnoid haemorrhage (SAH) for intracranial aneurysms, and has suggested that screening might cause harm. [source] Therapeutic mTOR Inhibition in Autosomal Dominant Polycystic Kidney Disease: What Is the Appropriate Serum Level?AMERICAN JOURNAL OF TRANSPLANTATION, Issue 7 2010G. Canaud Autosomal dominant polycystic kidney disease (ADPKD) is the most common inherited renal disease, and sirolimus, a mammalian target of rapamycin (mTOR) inhibitor, has been shown to significantly retard cyst expansion in animal models. The optimal therapeutic dose of sirolimus is not yet defined. Here, we report the history of a previously unknown ADPKD deceased donor whose kidneys were engrafted in two different recipients. One of the two received an immunosuppressive regimen based on sirolimus for 5 years while the other did not. After transplantation, both patients developed severe transplant cystic disease. Donor DNA sequence identified a new hypomorphic mutation in PKD1. The rate of cyst growth was identical in the two patients regardless of the treatment. While sirolimus treatment reduced the activation of mTOR in peripheral blood mononuclear cells, it failed to prevent mTOR activation in kidney tubular cells, this could account for the inefficiency of treatment on cyst growth. Together, our results suggest that the dose of sirolimus required to inhibit mTOR varies according to the tissue. [source] Mosaicism in Autosomal Dominant Polycystic Kidney Disease Revealed by Genetic Testing to Enable Living Related Renal TransplantationAMERICAN JOURNAL OF TRANSPLANTATION, Issue 1 2008A. Connor Patients with end-stage renal disease (ESRD) secondary to autosomal dominant polycystic kidney disease (ADPKD) receive fewer living-related kidney (LRK) transplants than other groups with ESRD. This relates to the difficulties in excluding the disease in potential donors. We report a case which highlights these difficulties and, by discovery of mosaicism for a new mutation, illustrates the role of clinical and molecular genetic resources in assessing young related kidney donors for patients with ADPKD. [source] Novel role for polycystin-1 in modulating cell proliferation through calcium oscillations in kidney cellsCELL PROLIFERATION, Issue 3 2008G. Aguiari Objectives: Polycystin-1 (PC1), a signalling receptor regulating Ca2+ -permeable cation channels, is mutated in autosomal dominant polycystic kidney disease, which is typically characterized by increased cell proliferation. However, the precise mechanisms by which PC1 functions on Ca2+ homeostasis, signalling and cell proliferation remain unclear. Here, we investigated the possible role of PC1 as a modulator of non-capacitative Ca2+ entry (NCCE) and Ca2+ oscillations, with downstream effects on cell proliferation. Results and discussion: By employing RNA interference, we show that depletion of endogenous PC1 in HEK293 cells leads to an increase in serum-induced Ca2+ oscillations, triggering nuclear factor of activated T cell activation and leading to cell cycle progression. Consistently, Ca2+ oscillations and cell proliferation are increased in PC1-mutated kidney cystic cell lines, but both abnormal features are reduced in cells that exogenously express PC1. Notably, blockers of the NCCE pathway, but not of the CCE, blunt abnormal oscillation and cell proliferation. Our study therefore provides the first demonstration that PC1 modulates Ca2+ oscillations and a molecular mechanism to explain the association between abnormal Ca2+ homeostasis and cell proliferation in autosomal dominant polycystic kidney disease. [source] | |||||||||||||