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Polycystic Kidney Disease (polycystic + kidney_disease)
Kinds of Polycystic Kidney Disease Selected AbstractsCAROLI'S SYNDROME AND ADULT POLYCYSTIC KIDNEY DISEASEANZ JOURNAL OF SURGERY, Issue 4 2007Susan Shedda Caroli's disease is a cystic disease of the liver, which has been rarely associated with adult onset polycystic kidney disease. Three cases have been reported in the English Medline search. The presentation of this fourth case discusses the issues surrounding the treatment of Caroli's disease in the setting of a renal transplant. [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] Polycystins: what polycystic kidney disease tells us about spermMOLECULAR REPRODUCTION & DEVELOPMENT, Issue 4 2004Abraham L. Kierszenbaum Abstract Experimental evidence indicates that the membrane-associated proteins polycystin-1 and polycystin-2 operate as a receptor-calcium channel complex that regulates signaling pathways essential for modulation of renal tubulogenesis. Polycystic kidney disease is characterized by defective renal tubular structure and results from mutations in either PKD1 or PKD2 genes. Recent data suggest that polycystin-1 and polycystin-2 might localize to primary cilium in principal cells of renal collecting tubules and are thought to act as mechanosensors of fluid flow and contents. Ciliary bending by fluid flow or mechanical stimulation induce Ca2+ release from intracellular stores, presumably to modulate ion influx in response to tubular fluid flow. Polycystins are also emerging as playing a significant role in sperm development and function. Drosophila polycystin-2 is associated with the head and tail of mature sperm. Targeted disruption of the PKD2 homolog results in nearly complete male sterility without disrupting spermatogenesis. Mutant sperm are motile but are unable to reach the female storage organs (seminal receptacles and spermathecae). The sea urchin polycystin-1-equivalent suPC2 colocalizes with the polycystin-1 homolog REJ3 to the plasma membrane over the acrosomal vesicle. This localization site suggests that the suPC2-REJ3 complex may function as a cation channel mediating acrosome reaction when sperm contact the jelly layer surrounding the egg at fertilization. Future studies leading to the identification of specific ligands for polycystins, including the signaling pathways, might define the puzzling relationship between renal tubular morphogenesis and sperm development and function. Mol. Reprod. Dev. 67: 385,388, 2004. © 2004 Wiley-Liss, Inc. [source] An epidemiological study of renal pathology in tuberous sclerosis complexBJU INTERNATIONAL, Issue 6 2004Finbar J. O'Callaghan OBJECTIVES To report the frequency of renal symptoms and complications of patients with tuberous sclerosis complex (TSC), to describe the ultrasonographic appearance of the kidneys in a population-based sample, and to investigate the relationship between a history of renal haemorrhage and renal lesions identified by ultrasonography. PATIENTS AND METHODS As part of an epidemiological study, 179 patients with TSC were identified as living in the Wessex Region in the South of England. Patients were interviewed and examined in their homes, to elicit the presence of renal symptoms or a history of renal complications. Renal ultrasonography was used in consenting patients in their homes. RESULTS There was a history of renal complications in 16 (9%) patients; 149 consented to interview and examination, and 19 gave a history of renal symptoms in the previous year; 124 had renal ultrasonography; 86 (69%) had renal angiomyolipomas and 37 (30%) had renal cysts. Large lesions (>3 cm in diameter) were strongly associated with a history of symptomatic bleeding, although significant haemorrhage occurred in a 6-year-old child with small angiomyolipomas. CONCLUSIONS The formation of angiomyolipoma in TSC is common. Polycystic kidney disease, renal carcinoma and renal failure, although rare, occur in TSC. Most patients with angiomyolipomas have neither complications nor symptoms. There was no appreciable difference between the sexes in the risk of developing these lesions. Although less commonly seen in the very young, there is no identifiable relationship after adolescence between age and the risk of having a renal angiomyolipoma. Bleeding tends to occur from large lesions (>3 cm) but most such patients have remained asymptomatic to date. [source] Transgenic mice expressing tamoxifen-inducible Cre for somatic gene modification in renal epithelial cellsGENESIS: THE JOURNAL OF GENETICS AND DEVELOPMENT, Issue 5 2006Irma S. Lantinga-van Leeuwen Abstract Gene inactivation often leads to an embryonic-lethal phenotype. In focal diseases like renal cell carcinomas and polycystic kidney disease, somatic gene inactivation in subsets of cells is likely to occur at later stages. We generated a transgenic mouse line with an inducible form of Cre recombinase for conditional gene modifications in kidney epithelial cells. To this end a 1.4-kb promoter fragment of the kidney-specific cadherin gene (KspCad) was cloned upstream of a tamoxifen-inducible Cre recombinase (CreERT2) encoding sequence. Expression and activity of Cre was evaluated using reverse transcriptase polymerase chain reaction (RT-PCR) analysis and by crossbreeding to Z/EG reporter mice. One KspCad-CreERT2 line showed kidney-specific Cre expression and mediated recombination upon tamoxifen treatment in Z/EG reporter mice. No reporter gene expression was detected in untreated animals or in extrarenal tissues upon treatment. Within the kidneys, enhanced green fluorescent protein (EGFP) fluorescence was observed in epithelial cells in several nephronic segments. In addition, the system successfully recombined a floxed Pkd1 gene. genesis 44:225,232, 2006. © 2006 Wiley-Liss, Inc. [source] A mouse model for cystic biliary dysgenesis in autosomal recessive polycystic kidney disease (ARPKD),HEPATOLOGY, Issue 5 2005Markus Moser Autosomal recessive polycystic kidney disease (ARPKD) is an important cause of liver- and renal-related morbidity and mortality in childhood. Recently, PKHD1, the gene encoding the transmembrane protein polyductin, was shown to be mutated in ARPKD patients. We here describe the first mouse strain, generated by targeted mutation of Pkhd1. Due to exon skipping, Pkhd1ex40 mice express a modified Pkhd1 transcript and develop severe malformations of intrahepatic bile ducts. Cholangiocytes maintain a proliferative phenotype and continuously synthesize TGF-,1. Subsequently, mesenchymal cells within the hepatic portal tracts continue to synthesize collagen, resulting in progressive portal fibrosis and portal hypertension. Fibrosis did not involve the hepatic lobules, and we did not observe any pathological changes in morphology or function of hepatocytes. Surprisingly and in contrast to human ARPKD individuals, Pkhd1ex40 mice develop morphologically and functionally normal kidneys. In conclusion,our data indicate that subsequent to formation of the embryonic ductal plate, dysgenesis of terminally differentiated bile ducts occurs in response to the Pkhd1ex40 mutation. The role of polyductin in liver and kidney may be functionally divergent, because protein domains essential for bile duct development do not affect nephrogenesis in our mouse model. Supplementary material for this article can be found on the HEPATOLOGYwebsite (http://www.interscience.wiley.com/jpages/0270-9139/suppmat/index.html). (HEPATOLOGY 2005.) [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] Pregnancy complicated by Caroli's disease with polycystic kidney disease: A case report and following observationsJOURNAL OF OBSTETRICS AND GYNAECOLOGY RESEARCH (ELECTRONIC), Issue 4pt2 2008Mika Tsunoda Abstract Caroli's disease and Caroli's syndrome are rare congenital disorders characterized by non-obstructive cystic dilatation of the intrahepatic bile ducts. These disorders are often associated with autosomal recessive polycystic kidney disease. A young woman at 11 weeks of gestation was referred to our hospital for proper management of Caroli's disease during pregnancy. Magnetic resonance imaging and laboratory tests revealed Caroli's disease with chronic renal failure caused by polycystic kidney disease. She received diet control, erythropoietin and prophylactic oral antibiotics. Her pregnancy course was uneventful, and she gave birth at 37 weeks of gestation. Thereafter, her renal function gradually worsened. Hemodialysis was begun 5 years after parturition. Though the courses of pregnancies complicated by Caroli's disease or Caroli's syndrome are variable and can include life-threatening conditions, uneventful outcomes can be expected if careful management prevents biliary and renal infection. [source] Polycystins: what polycystic kidney disease tells us about spermMOLECULAR REPRODUCTION & DEVELOPMENT, Issue 4 2004Abraham L. Kierszenbaum Abstract Experimental evidence indicates that the membrane-associated proteins polycystin-1 and polycystin-2 operate as a receptor-calcium channel complex that regulates signaling pathways essential for modulation of renal tubulogenesis. Polycystic kidney disease is characterized by defective renal tubular structure and results from mutations in either PKD1 or PKD2 genes. Recent data suggest that polycystin-1 and polycystin-2 might localize to primary cilium in principal cells of renal collecting tubules and are thought to act as mechanosensors of fluid flow and contents. Ciliary bending by fluid flow or mechanical stimulation induce Ca2+ release from intracellular stores, presumably to modulate ion influx in response to tubular fluid flow. Polycystins are also emerging as playing a significant role in sperm development and function. Drosophila polycystin-2 is associated with the head and tail of mature sperm. Targeted disruption of the PKD2 homolog results in nearly complete male sterility without disrupting spermatogenesis. Mutant sperm are motile but are unable to reach the female storage organs (seminal receptacles and spermathecae). The sea urchin polycystin-1-equivalent suPC2 colocalizes with the polycystin-1 homolog REJ3 to the plasma membrane over the acrosomal vesicle. This localization site suggests that the suPC2-REJ3 complex may function as a cation channel mediating acrosome reaction when sperm contact the jelly layer surrounding the egg at fertilization. Future studies leading to the identification of specific ligands for polycystins, including the signaling pathways, might define the puzzling relationship between renal tubular morphogenesis and sperm development and function. Mol. Reprod. Dev. 67: 385,388, 2004. © 2004 Wiley-Liss, Inc. [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] Review: The role of microRNAs in kidney diseaseNEPHROLOGY, Issue 6 2010JORDAN YZ LI ABSTRACT MicroRNAs (miRNAs) are short non-coding RNAs that modulate physiological and pathological processes by inhibiting target gene expression via blockade of protein translation or by inducing mRNA degradation. These miRNAs potentially regulate the expression of thousands of proteins. As a result, miRNAs have emerged rapidly as a major new area of biomedical research with relevance to kidney disease. MiRNA expression has been shown to differ between the kidney and other organs as well as between different kidney regions. Furthermore, miRNAs have been found to be functionally important in models of podocyte development, diabetic nephropathy and polycystic kidney disease. Of particular interest, podocyte-specific deletion of Dicer, a key enzyme in the biogenesis of miRNA, results in proteinuria and severe renal impairment in mice. One miRNA (miR-192) can also act as an effector of transforming growth factor-, activity in the high-glucose environment of diabetic nephropathy. Differential expression of miRNAs has been reported in kidney allograft rejection. It is anticipated that future studies involving miRNAs will generate new insights into the complex pathophysiology underlying various kidney diseases, generate diagnostic biomarkers and might be of value as therapeutic targets for progressive kidney diseases. The purpose of this review is to highlight key miRNA developments in kidney diseases and how this might influence the diagnosis and management of patients with kidney disease in the future. [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] Rothia dentocariosa sepsis in a pediatric renal transplant recipient having post-transplant lymphoproliferative disordersPEDIATRIC TRANSPLANTATION, Issue 3 2006Silke Wiesmayr Abstract: Background: Rothia dentocariosa (RD) is a Gram-positive rod that colonizes the human oral cavity and can cause infective endocarditis. Result: We report on a six-yr-old boy who underwent renal transplantation for polycystic kidney disease at the age of eight months. He developed post-transplant lymphoproliferative disorders after four yr and progressive graft failure. Following chemotherapy, the patient presented with neutropenia and sepsis. RD was isolated from blood and treatment with piperacillin/tazobactam was initiated; however, the child died because of multiorgan failure. Discussion: To the best of our knowledge, this is the first case of RD sepsis in a pediatric solid organ transplant recipient. [source] Disease Stage Characterization of Hepatorenal Fibrocystic Pathology in the PCK Rat Model of ARPKDTHE ANATOMICAL RECORD : ADVANCES IN INTEGRATIVE ANATOMY AND EVOLUTIONARY BIOLOGY, Issue 8 2010Stephen B. Mason Abstract The rat Pck gene is orthologous to the human PKHD1 gene responsible for autosomal recessive polycystic kidney disease (ARPKD). Both renal and hepatic fibrocystic pathology occur in ARPKD. Affected humans have a variable rate of progression, from morbidly affected infants to those surviving into adulthood. This study evaluated the PCK rat, a model of slowly progressive ARPKD. This model originated in Japan and was rederived to be offered commercially by Charles River Laboratories (Wilmington, MA). Previous studies have described the basic aspects of PCK pathology from privately held colonies. This study provides a comprehensive characterization of rats from those commercially available. Rats were bred, maintained on a 12:12 hr light/dark cycle, fed (7002 Teklad), and water provided ad libitum. Male and female rats were evaluated from 4 through 35 weeks of age with histology and serum chemistry. As the hepatorenal fibrocystic disease progressed beyond 18 weeks, the renal pathology (kidney weight, total cyst volume) and renal dysfunction (BUN and serum creatinine) tended to be more severe in males, whereas liver pathology (liver weight as % of body weight and hepatic fibrocystic volume) tended to be more severe in females. Hyperlipidemia was evident in both genders after 18 weeks. Bile secretion was increased in PCK rats compared with age-matched Sprague Dawley rats. The PCK is an increasingly used orthologous rodent model of human ARPKD. This characterization study of hepatorenal fibrocystic pathology in PCK rats should help researchers select stages of pathology to study and/or monitor disease progression during their longitudinal studies. Anat Rec 293:1279,1288, 2010. © 2010 Wiley-Liss, Inc. [source] Embolization of Polycystic Kidneys as an Alternative to Nephrectomy Before Renal Transplantation: A Pilot StudyAMERICAN JOURNAL OF TRANSPLANTATION, Issue 10 2010F. Cornelis In autosomal polycystic kidney disease, nephrectomy is required before transplantation if kidney volume is excessive. We evaluated the effectiveness of transcatheter arterial embolization (TAE) to obtain sufficient volume reduction for graft implantation. From March 2007 to December 2009, 25 patients with kidneys descending below the iliac crest had unilateral renal TAE associated with a postembolization syndrome protocol. Volume reduction was evaluated by CT before, 3, and 6 months after embolization. The strategy was considered a success if the temporary contraindication for renal transplantation could be withdrawn within 6 months after TAE. TAE was well tolerated and the objective was reached in 21 patients. The temporary contraindication for transplantation was withdrawn within 3 months after TAE in 9 patients and within 6 months in 12 additional patients. The mean reduction in volume was 42% at 3 months (p = 0.01) and 54% at 6 months (p = 0.001). One patient required a cyst sclerosis to reach the objective. The absence of sufficient volume reduction was due to an excessive basal renal volume, a missed accessory artery and/or renal artery revascularization. Embolization of enlarged polycystic kidneys appears to be an advantageous alternative to nephrectomy before renal transplantation. [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] Successful Management of Eviscerated Renal Allograft with Preservation of FunctionAMERICAN JOURNAL OF TRANSPLANTATION, Issue 5 2008H. Jeon Although most wound complications after renal transplantation are minor, the renal allograft, in its superficial and extraperitoneal location, is vulnerable to exposure if there is wound breakdown resulting in loss of overlying tissue. We describe a 66-year-old man who received a renal allograft from a deceased donor for end-stage renal disease (ESRD) secondary to polycystic kidney disease. His immediate posttransplant course was complicated by delayed graft function from acute tubular necrosis, reexploration for perigraft hematoma and subsequent wound dehiscence. After unsuccessful conservative wound care, the renal allograft became completely eviscerated due to fascial retraction of the dehisced wound. While the allograft was initially covered with a pedicled rectus femoris muscle flap, several local tissue rearrangements were required for definitive coverage. The allograft function was recovered after initial flap coverage and was subsequently maintained; follow-up more than 2 years after transplantation has demonstrated not only continued stable graft function but also complete healing of the dehiscent wound. [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] Linkage confirms canine pkd1 orthologue as a candidate for bull terrier polycystic kidney diseaseANIMAL GENETICS, Issue 4 2009C. A. O'Leary Summary Bull terrier polycystic kidney disease (BTPKD) is a Mendelian disorder with many features reminiscent of human autosomal dominant polycystic disease, the latter disease being due to mutations at PKD1 and PKD2 loci. We investigated the role of the canine pkd1 orthologue in BTPKD via linkage analysis of a large kindred in which the disorder is segregating. Twelve microsatellite markers around the canine pkd1 locus (CFA6) were amplified from the genomic DNA of 20 affected and 16 unaffected bull terriers. An additional 28 affected dogs were genotyped at five key microsatellites. A highly significant multi-point LOD score that peaked over the canine pkd1 locus was observed (LOD = 6.59, best two-point LOD score LOD = 6.02), implicating this as the BTPKD locus. [source] CAROLI'S SYNDROME AND ADULT POLYCYSTIC KIDNEY DISEASEANZ JOURNAL OF SURGERY, Issue 4 2007Susan Shedda Caroli's disease is a cystic disease of the liver, which has been rarely associated with adult onset polycystic kidney disease. Three cases have been reported in the English Medline search. The presentation of this fourth case discusses the issues surrounding the treatment of Caroli's disease in the setting of a renal transplant. [source] Complementary roles of prenatal sonography and magnetic resonance imaging in diagnosis of fetal renal anomaliesAUSTRALIAN AND NEW ZEALAND JOURNAL OF OBSTETRICS AND GYNAECOLOGY, Issue 3 2010Ibrahim A. ABDELAZIM Objectives:, This study was designed to assess the role of magnetic resonance imaging (MRI) in refining the diagnosis of prenatally suspected fetal renal abnormalities following screening ultrasound. Patients and methods:, Twenty pregnant women, with suspected fetal renal abnormality detected during screening ultrasound and more than 14 weeks' gestation, were included in this observational prospective study at Ain Shams University Maternity Hospital from March 2004 to March 2005 after informed consent and after approval of the study protocol by the institute ethics committee. Results:, The MRI could diagnose correctly 10 cases of hydronephrosis, one case of polycystic kidney disease (PCKD), one case of RA, two normal case and two cases of intra-abdominal masses (IA Mass) (16 of 18 cases). The prenatal ultrasound could diagnose correctly eight cases of hydronephrosis, one case of PCKD, one case of renal agenesis, one case of multicystic kidney disease and one case of IA Mass (12 of 18 cases). The prenatal ultrasound and MRI gave different diagnoses in eight cases and gave the same diagnosis in 12 cases. The MRI could diagnose the aetiology of congenital renal cysts in 10 of the 20 studied cases (50%). Conclusion:, Magnetic resonance imaging can be used as a complementary tool in the assessment of sonographically suspected fetal renal anomalies. [source] Auscultation and echocardiographic findings in Bull Terriers with and without polycystic kidney diseaseAUSTRALIAN VETERINARY JOURNAL, Issue 5 2005CA O'LEARY Objective To investigate a possible association between Bull Terrier polycystic kidney disease (BTPKD) and cardiac disease, to determine the prevalence of mitral valve disease (MVD) and left ventricular outflow tract obstruction (LVOTO) in the Australian Bull Terrier population, and to compare auscultation and echocardiography in detection of cardiac disease in Bull Terriers. Design Ninety-nine Bull Terriers, ranging in age from 8 weeks to 13 years and 11 months were auscultated and examined using renal ultrasonography; 86 were also examined using echocardiography. The prevalence and severity of heart defects in dogs with BTPKD was compared with that in dogs without BTPKD. Results Nineteen of these 99 dogs were diagnosed with BTPKD. Forty-two percent of Bull Terriers with BTPKD and 28% of those without BTPKD had murmurs characteristic of mitral regurgitation or LVOTO. How recently an animal was descended from an ancestor with BTPKD was associated with presence (P = 0.008) and loudness of a murmur (P = 0.009). Overall, echocardiography detected MVD in 39% of Bull Terriers, with increased prevalence in older animals (P = 0.003). Mitral stenosis was found in eight cases. Fifty-three percent of dogs in this study had evidence of LVOTO, with obstruction consisting of a complex of lesions including dynamic or fixed subvalvular LVOTO, significantly narrowed left ventricular outflow tract or valvular aortic stenosis. Dogs with BTPKD, or those descended from dogs with BTPKD, were more likely to have MVD (P = 0.006), and while LVOTO was not more common in these dogs, if they did have LVOTO, they were more likely to have severe obstruction than dogs with no ancestors with BTPKD (analysed in three ways P = 0.028 to 0.001). In this study, 46% of Bull Terriers without a murmur or arrhythmia had cardiac disease detected on echocardiographic examination. Conclusion Cardiac disease, especially MVD and LVOTO, was common in Bull Terriers in this study, and those with BTPKD had an increased risk of cardiac abnormalities. Auscultation did not detect a significant number of Bull Terriers with cardiac disease. [source] Renal pathology of polycystic kidney disease and concurrent hereditary nephritis in Bull TerriersAUSTRALIAN VETERINARY JOURNAL, Issue 6 2002CA O'LEARY Objective To describe the renal lesions in Bull Terrier poly-cystic kidney disease (BTPKD), to confirm that the renal cysts in BTPKD arise from the nephron or collecting tubule, and to identify lesions consistent with concurrent BTPKD and Bull Terrier hereditary nephritis (BTHN). Design Renal tissue from five Bull Terriers with BTPKD and eight control dogs was examined by light and transmission electron microscopy. Clinical data were collected from all dogs, and family history of BTPKD and BTHN for all Bull Terriers. Results In BTPKD the renal cysts were lined by epithelial cells of nephron or collecting duct origin that were usually squamous or cuboidal, with few organelles. They had normal junctional complexes, and basal laminae of varying thicknesses. Glomeruli with small, atrophic tufts and dilated Bowman's capsules, tubular loss and dilation, and interstitial inflammation and fibrosis were common. Whereas the lesions seen in BTHN by light microscope were nonspecific, the presence of characteristic ultrastructural glomerular basement membrane (GMB) lesions and a family history of this disease indicated concurrent BTHN was likely in three of five cases of BTPKD. Conclusion This paper provides evidence that renal cysts in BTPKD are of nephron or collecting duct origin. In addition, GBM lesions are described that strongly suggest that BTPKD and BTHN may occur simultaneously. [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] Pseudoexon activation in the PKHD1 gene: a French founder intronic mutation IVS46+653A>G causing severe autosomal recessive polycystic kidney diseaseCLINICAL GENETICS, Issue 2 2009L Michel-Calemard First page of article [source] Liver and kidney disease in ciliopathies,,AMERICAN JOURNAL OF MEDICAL GENETICS, Issue 4 2009Meral Gunay-Aygun§ Abstract Hepatorenal fibrocystic diseases (HRFCDs) are among the most common inherited human disorders. The discovery that proteins defective in the autosomal dominant and recessive polycystic kidney diseases (ADPKD and ARPKD) localize to the primary cilia and the recognition of the role these organelles play in the pathogenesis of HRFCDs led to the term "ciliopathies." While ADPKD and ARPKD are the most common ciliopathies associated with both liver and kidney disease, variable degrees of renal and/or hepatic involvement occur in many other ciliopathies, including Joubert, Bardet,Biedl, Meckel,Gruber, and oral,facial,digital syndromes. The ductal plate malformation (DPM), a developmental abnormality of the portobiliary system, is the basis of the liver disease in ciliopathies that manifest congenital hepatic fibrosis (CHF), Caroli syndrome (CS), and polycystic liver disease (PLD). Hepatocellular function remains relatively preserved in ciliopathy-associated liver diseases. The major morbidity associated with CHF is portal hypertension (PH), often leading to esophageal varices and hypersplenism. In addition, CD predisposes to recurrent cholangitis. PLD is not typically associated with PH, but may result in complications due to mass effects. The kidney pathology in ciliopathies ranges from non-functional cystic dysplastic kidneys to an isolated urinary concentration defect; the disorders contributing to this pathology, in addition to ADPKD and ARPKD, include nephronophithisis (NPHP), glomerulocystic kidney disease and medullary sponge kidneys. Decreased urinary concentration ability, resulting in polyuria and polydypsia, is the first and most common renal symptom in ciliopathies. While the majority of ADPKD, ARPKD, and NPHP patients require renal transplantation, the frequency and rate of progression to renal failure varies considerably in other ciliopathies. This review focuses on the kidney and liver disease found in the different ciliopathies. Published 2009 Wiley-Liss, Inc. [source] | |||||||||||||||||||||||||