Autosomal Polycystic Kidney Disease Research Articles

Functional Abnormalities and Thyroid Nodules in Patients with End-stage Renal Disease.

Clinical and subclinical hypothyroidism is more common in patients with end-stage renal disease (ESRD) than in the general population. Patients with ESRD with hypothyroidism are more susceptible to cardiovascular disease, with an increased risk of mortality than those with normal thyroid function. Moreover, these patients have higher incidence of benign and malignant nodules. This was a retrospective study on 2,147 patients with ESRD on the renal transplant waiting list between 2000 and 2015 aimed at identifying the presence of hypothyroidism and associated variables. Hypothyroidism was detected in 437/2,147 (20.3%) patients, 289 of them having the subclinical form. Cardiovascular disease and older age were significantly associated with hypothyroidism, and autosomal polycystic kidney disease was correlated to goiter (p<0.001). Thyroid abnormalities, particularly hypothyroidism with nodules, should be investigated in patients with ESRD on a waiting list for renal transplant to control cardiovascular complications and cancer risk.

Profiling of miRNAs and target genes related to cystogenesis in ADPKD mouse models

Autosomal polycystic kidney disease (ADPKD) is a common inherited renal disease characterized by the development of numerous fluid-filled cysts in both kidneys. We investigated miRNA-mediated regulatory systems and networks that play an important role during cystogenesis through integrative analysis of miRNA- and RNA-seq using two ADPKD mouse models (conditional Pkd1- or Pkd2-deficient mice), at three different time points (P1, P3, and P7). At each time point, we identified 13 differentially expressed miRNAs (DEmiRs) and their potential targets in agreement with cyst progression in both mouse models. These targets were involved in well-known signaling pathways linked to cystogenesis. More specifically, we found that the actin cytoskeleton pathway was highly enriched and connected with other well-known pathways of ADPKD. We verified that miR-182-5p regulates actin cytoskeleton rearrangement and promotes ADPKD cystogenesis by repressing its target genes—Wasf2, Dock1, and Itga4—in vitro and in vivo. Our data suggest that actin cytoskeleton may play an important role in renal cystogenesis, and miR-182-5p is a novel regulator of actin cytoskeleton and cyst progression. Furthermore, this study provides a systemic network of both key miRNAs and their targets associated with cyst growth in ADPKD.

Misdiagnosis of Caroliʼs Disease: A Case Report

Caroli's disease (CD) is a rare inherited condition characterized by localized or diffused, multifocal, segmental dilatation of the intrahepatic bile ducts. Caroli's syndrome (CS) is a more complex form of a disease associated with congenital hepatic fibrosis (CHF) and often accompanied by cholangiocarcinoma, calculi of the intrahepatic duct, cholangitis, pancreatic cyst, and various renal disorders including autosomal polycystic kidney disease (PKD), medullary sponge kidney and medullary cystic disease. A 41-years-old man presented with high fever, chills, fatigue, nausea, vomiting, and pain in right upper abdominal quadrant. Physical examination showed poor general state, tachycardia, mild icterus and hepatosplenomegaly. Laboratory evaluation (Table 1) revealed increased parameters of acute inflammation, liver and kidney function tests; MRCP showed hepatosplenomegaly, multiple cysts in both kidneys with reduced parenchyma, and diffuse cystic/fusiform dilatation of the intrahepatic bile ducts (Image 1 and 2). As 9-month-old infant, he experienced first episode of pyelonephritis that became recurrent and accompanied with vesicoureteral reflux, resulted in chronic renal insufficiency diagnosed 23 years ago. Althought hepatosplenomegaly was verified in early childhood, no further testing were performed. During time, our patient developed recurrent cholangitis but without clear consensus between radiologist and gastroenterohepatologists about pathological substrate - CD, CS or primary sclerosing cholangitis (PSC), although MRCP was performed several times. Liver biopsy in 2007 showed multiple bile duct hamartomas (MBH), without evidence of CHF. Endoscopic retrograde cholangiopancreatography (ERCP) was performed in 2008, and endoscopist reported changes in bile duct suggesting PSC. In order to resolve the diagnostic dilemma, after resolving current episode, genetic testing (exome sequencing) was carried out, now we waiting the results. Based on recurrent cholangitis, cystic dilatation of the intrahepatic bile ducts associated with PKD, normal findings on extrahepatic bile ducts, and presence of MBH, we concluded that our patient most likely has CS. In some cases MRCP, ERCP, not even liver biopsy is not sufficient to clearly diagnose CD; in this case genetic analysis may be helpful. In children and adult patients who present with recurrent cholangitist and hepato/splenomegaly or in all cases with cholagitis and PKD, we must consider CD or CS.Table: Table. Laboratory Data on Admission to the HospitalFigure: MRCP, frontal section: Diffuse cystic/fusiform dilatation of the intrahepatic bile ducts, but more in the left lobe, with enlarged polycystic kidneys.Figure: MRCP reconstruction of the biliary tree: Multiple cystic dilatations communicating with intrahepatic biliary tree and normal caliber of common choledochal duct.

THU-418 - Clinical outcomes in polycystic liver disease comparing autosomal dominant polycystic liver disease with autosomal polycystic kidney disease: results of the PLD registry

THU-418 - Clinical outcomes in polycystic liver disease comparing autosomal dominant polycystic liver disease with autosomal polycystic kidney disease: results of the PLD registry

Polycystins and intercellular mechanotransduction: A precise dosage of polycystin 2 is necessary for alpha-actinin reinforcement of junctions upon mechanical stimulation

Polycystins 1 and 2, which are mutated in Autosomal Polycystic Kidney Disease, are involved in mechanotransduction through various mechanisms. In renal cells, polycystins not only have an important mechanotransductive role in primary cilia but are also present in intercellular contacts but their role there remains unclear. Here, we address the hypothesis that polycystins are involved in mechanotransduction via intercellular junctions, which would be expected to have consequences on tissue organization. We focused on the role of polycystin 2, which could be involved in mechanical organization at junctions either by its channel activity or by the direct recruitment of cytoskeleton components such as the F-actin cross-linker α-actinin. After mechanical stimulation of intercellular junctions in MDCK renal epithelial cells, α-actinin is rapidly recruited but this is inhibited upon overexpression of PC2 or the D509V mutant that lacks channel activity, and is also decreased upon PC2 silencing. This suggests that a precise dosage of PC2 is necessary for an adequate mechanosensitive α-actinin recruitment at junctions. At the multicellular level, a change in PC2 expression was associated with changes in velocity in confluent epithelia and during wound healing together with a loss of orientation. This study suggests that the mechanosensitive regulation of cytoskeleton by polycystins in intercellular contacts may be important in the context of ADPKD.

ECE1 gene variant shows tendency toward chronic kidney disease advancement among autosomal polycystic kidney disease patients

Background/PurposeAutosomal dominant polycystic kidney disease (ADPKD) is characterized by numerous epithelium-lined cysts in the kidney and is the leading genetic cause of end-stage renal disease worldwide. Endothelin-1 is a potent vasoactive peptide implicated in the regulation of basal vascular tone. Endothelin (ET)-converting enzyme 1 (ECE1) is well known for its critical role in the process of ET. MethodsWe investigated ECE1 gene variants to unravel ECE1 modifier effects associated with renal disease progression in ADPKD. Three ECE1 functional polymorphisms [rs213046 (−839 A>C), rs213045 (−338 G>T), and rs1076669 (Thr338Ile)] were genotyped using a fluorescence resonance energy transfer-based KASPar method in 106 ADPKD patients and 112 healthy participants. A Chi-square test was used to determine the relationship between ADPKD and ECE1 variants, and multivariate logistic regression analysis was performed to assess the effect of ECE1 variants on chronic kidney disease (CKD) progression. Mantel-Haenszel stratified analysis was performed to assess relationships between different CKD stages, hypertension, and their interaction. ResultsAll loci are polymorphic and followed a Hardy-Weinberg equilibrium. Distribution of ECE1 genotypes in controls and ADPKD groups was not statistically significant, and linkage disequilibrium was not strong between pairs of single-nucleotide polymorphisms. The rs213046 variant genotypes were overrepresented in advanced CKD stages (p = 0.031). ConclusionSignificant confounding effects of hypertension on CKD progression in ADPKD were observed. These results suggested that the ECE1 gene variant is a modifier of CKD advancement among ADPKD patients. 背景自體顯性多囊性腎病 (ADPKD) 的特點，是腎臟呈現相當多由上皮構成的囊腫，在全球是導致末期腎病 (ESRD) 的主要遺傳性原因。Endothelin-1 (ET-1) 是一種具有高度血管活性的胜肽，被認為與基礎血管張力的調節有關。眾所周知，endothelin (ET) 轉化酵素 1 (ECE1) 則在 ET 代謝上佔有重要的角色。 方法在本研究中，我們調查了在 ADPKD 患者間，ECE1 基因變體與 CKD 病情發展的可能關聯。我們採用以 FRET 為基礎的 KASPar 方法，對 106 位 ADPKD 患者及 112 位健康人士，作出 3 種 ECE1 功能性多態性 [rs213046 (-839 A>C)、rs213045 (-338 G>T) 及 rs1076669 (Thr338Ile)] 的基因型辨識。對於 ADPKD 與 ECE1 基因變體的關聯，我們採取卡方檢驗；ECE1 基因變體與 CKD 病情發展的關聯，以多變項邏輯迴歸進行分析；CKD 分期與高血壓的關聯及兩者的交互作用，則採用 Mantel-Haenszel 分層分析。 結果所有基因座 (loci) 均呈現多態性，且遵循 Hardy-Weinberg 平衡。ADPKD 患者與對照組間的 ECE1 基因型分佈並無明顯差別。單核苷酸多態性鹼基對 (SNP pairs) 之間，並未呈現出明顯的連鎖不平衡 (LD)。在晚期 CKD 患者間，rs213046 變體基因型呈現過度的表達 (p = 0.031)。 結論我們觀察到，在 ADPKD 患者間，高血壓是 CKD 病情發展的一個明顯的干擾因素。以上結果意味著，在 ADPKD 患者間，ECE1 基因變體可影響 CKD 的病情發展。

An autopsy case of vertebrobasilar dolichoectasia under hemodialysis due to autosomal dominant polycystic kidney disease.

A 60-year-old male with end-stage kidney disease due to autosomal polycystic kidney disease began maintenance hemodialysis in 2005. A brain CT scan showed dilatation of left vertebral artery, basilar artery, bilateral post cerebral artery, and middle cerebral artery. At the time, he was diagnosed as vertebrobasilar dolichoectasia. He was once admitted to our hospital for ischemic stroke. After discharge, he was treated with anticoagulant agent from 2010 to 2012 without any new stroke events. In March, 2012, he was admitted to our hospital for an evaluation of diplopia and left hemiplegia. Brain MRI showed acute ischemia of bilateral pons and right temporal lobe. He was once recovered with urokinase and argatroban, but 3 months after admission, he died with sudden hypotension and impaired consciousness. Autopsy revealed that subarachnoid hemorrhage due to the rupture of basilar artery aneurysm was responsible for this event.

Soluble receptor for advanced glycation end products inhibits disease progression in autosomal dominant polycystic kidney disease by down-regulating cell proliferation.

Autosomal polycystic kidney disease (ADPKD) is a highly prevalent genetic renal disorder in which epithelial-lining fluid-filled cysts appear in kidneys. It is accompanied by hyperactivation of cell proliferation, interstitial inflammation, and fibrosis around the cyst lining cells, finally reaching end-stage renal disease. Previously, we found high expression of ligands stimulating the receptor for advanced glycation end products (RAGE) in ADPKD mice. Furthermore, gene silencing of RAGE was revealed to cause reduction of cystogenesis via down-regulation of cell proliferation in vitro, and intravenous administration of anti-RAGE adenovirus in vivo also displayed alleviation of the disease. Here, we attempted to identify the role of soluble RAGE (sRAGE) in inhibiting the progression of ADPKD using 2 different ADPKD mouse models. sRAGE is an endogenously expressed form of RAGE that has no membrane-anchoring domain, thereby giving it the ability to neutralize the ligands that stimulate RAGE signals. Both overexpression of sRAGE and sRAGE treatment blocked RAGE-mediated cell proliferation in vitro. In addition, sRAGE-injected ADPKD mice showed reduced cysts accompanied by enhanced renal function, inhibition of cell proliferation, inflammation, and fibrosis. These positive therapeutic effects of sRAGE displayed little liver toxicity, suggesting it as a new potential therapeutic target of ADPKD with low side effects.

Blockade of interleukin-8 receptor signalling inhibits cyst development in vitro, via suppression of cell proliferation in autosomal polycystic kidney disease.

Autosomal dominant polycystic kidney disease (ADPKD) is a highly prevalent inherited disorder and results in the progressive development of cysts in both kidneys. In recent studies, several cytokines and growth factors secreted by the cyst-lining epithelia were identified to be upregulated and promote cyst growth. According to our previous study, chemokines with a similar amino acid sequence as human interleukin-8 (IL-8) are highly expressed in a rodent model with renal cysts. Therefore, in this study, we focused on whether IL-8 signalling is associated with renal cyst formation, and tested the possibility of IL-8 as a new therapeutic target for ADPKD. Expression of IL-8 and its receptor were screened either by enzyme linked immunosorbent assay (ELISA) or Western blot. Inhibited IL-8 signalling by antagonist for IL-8 receptor or gene silencing was tested in molecular levels, mainly through Western blot. And cell proliferation was measured by XTT assays. Finally, a three-dimensional culture was performed to understand how IL-8 affected cyst formation, in vitro. Interleukin-8 secretion and expression of its receptor highly increased in two different human ADPKD cell lines (WT9-7 and WT9-12), compared to normal human renal cortical epithelial cell line. Cell proliferation, which is mediated by IL-8 signal, was inhibited either by an antagonist or siRNA targeting for IL-8 receptor. Finally, a three-dimensional culture showed an alleviation of cystogenesis in vitro, after blocking the IL-8 receptor signals. These results suggest that IL-8 and its signalling molecules could be new biomarkers and a therapeutic target of ADPKD.

Copeptin (CTproAVP), a new tool for understanding the role of vasopressin in pathophysiology.

Arginine vasopressin (AVP) plays a key role in many physiologic and pathologic processes. The most important stimulus for AVP release is a change in plasma osmolality. AVP is also involved in the response and adaptation to stress. Reliable measurement of AVP is hindered by several factors. Over 90% of AVP is tightly bound to platelets, and its estimation is influenced by the number of platelets, incomplete removal of platelets or pre-analytical processing steps. Copeptin (CTproAVP), a 39-aminoacid glycopeptide, is a C-terminal part of the precursor pre-provasopressin (pre-proAVP). Activation of the AVP system stimulates CTproAVP secretion into the circulation from the posterior pituitary gland in equimolar amounts with AVP. Therefore CTproAVP directly reflects AVP concentration and can be used as a surrogate biomarker of AVP secretion. In many studies CTproAVP represents AVP levels and its behavior represents changes in plasma osmolality, stress and various disease states, and shows some of the various physiologic and pathophysiologic conditions associated with increased or decreased AVP. Increased CTproAVP concentration is described in several studies as a strong predictor of mortality in patients with chronic heart failure and acute heart failure. Autosomal polycystic kidney disease (ADPKD) patients have both central and nephrogenic defects in osmoregulation and CTproAVP balance. A possibility raised by these clinical observations is that CTproAVP may serve to identify patients who could benefit from an intervention aimed at countering AVP.

A New PKD1 Mutation Discovered in a Chinese Family with Autosomal Polycystic Kidney Disease

Background/Aims: Autosomal-dominant polycystic kidney disease (ADPKD), a heterogeneous genetic disorder characterized by massive kidney enlargement and progressive chronic kidney disease, is due to abnormal proliferation of renal tubular epithelium. ADPKD is known to be caused by mutations in PKD1 and PKD2 genes. Methods: In the present study, the mutation analysis of PKD genes was performed in a new Chinese family with ADPKD using Long-Range (LR) PCR sequencing and targeted next-generation sequencing (targeted DNA-HiSeq). Results: A unique 28 bp deletion (c.12605_12632del28) in exon 46 of the PKD1 gene was identified in two affected family members by LR PCR method, but not in any unaffected relatives or unrelated controls. Higher accuracy and less missing detection presented in LR PCR method compared with targeted DNA-HiSeq. This mutation c.12605_12632del28 (p.Arg4202ProextX146) resulted in a delayed termination of amino acid code, and was highly speculated pathogenic in this ADPKD family. Moreover, this newly identified frame-shift change was compared to the PKD gene database, but no similar mutation was yet reported. Conclusion: A novel frame-shift mutation, c. 12605_12632del28, in the PKD1 gene was found in a Chinese ADPKD family. All evidence available suggested that it might be the mutation responsible for the disease in that family.

Genetically modified pigs to model human diseases

Genetically modified mice are powerful tools to investigate the molecular basis of many human diseases. Mice are, however, of limited value for preclinical studies, because they differ significantly from humans in size, general physiology, anatomy and lifespan. Considerable efforts are, thus, being made to develop alternative animal models for a range of human diseases. These promise powerful new resources that will aid the development of new diagnostics, medicines and medical procedures. Here, we provide a comprehensive review of genetically modified porcine models described in the scientific literature: various cancers, cystic fibrosis, Duchenne muscular dystrophy, autosomal polycystic kidney disease, Huntington’s disease, spinal muscular atrophy, haemophilia A, X-linked severe combined immunodeficiency, retinitis pigmentosa, Stargardt disease, Alzheimer’s disease, various forms of diabetes mellitus and cardiovascular diseases.

Parallel Analysis of mRNA and microRNA Microarray Profiles to Explore Functional Regulatory Patterns in Polycystic Kidney Disease: Using PKD/Mhm Rat Model

Autosomal polycystic kidney disease (ADPKD) is a frequent monogenic renal disease, characterised by fluid-filled cysts that are thought to result from multiple deregulated pathways such as cell proliferation and apoptosis. MicroRNAs (miRNAs) are small non-coding RNAs that regulate the expression of many genes associated with such biological processes and human pathologies. To explore the possible regulatory role of miRNAs in PKD, the PKD/Mhm (cy/+) rat, served as a model to study human ADPKD. A parallel microarray-based approach was conducted to profile the expression changes of mRNAs and miRNAs in PKD/Mhm rats. 1,573 up- and 1,760 down-regulated genes were differentially expressed in PKD/Mhm. These genes are associated with 17 pathways (such as focal adhesion, cell cycle, ECM-receptor interaction, DNA replication and metabolic pathways) and 47 (e.g., cell proliferation, Wnt and Tgfβ signaling) Gene Ontologies. Furthermore, we found the similar expression patterns of deregulated genes between PKD/Mhm (cy/+) rat and human ADPKD, PKD1L3/L3, PKD1−/−, Hnf1α-deficient, and Glis2lacZ/lacZ models. Additionally, several differentially regulated genes were noted to be target hubs for miRNAs. We also obtained 8 significantly up-regulated miRNAs (rno-miR-199a-5p, −214, −146b, −21, −34a, −132, −31 and −503) in diseased kidneys of PKD/Mhm rats. Additionally, the binding site overrepresentation and pathway enrichment analyses were accomplished on the putative targets of these 8 miRNAs. 7 out of these 8 miRNAs and their possible interactions have not been previously described in ADPKD. We have shown a strong overlap of functional patterns (pathways) between deregulated miRNAs and mRNAs in the PKD/Mhm (cy/+) rat model. Our findings suggest that several miRNAs may be associated in regulating pathways in ADPKD. We further describe novel miRNAs and their possible targets in ADPKD, which will open new avenues to understand the pathogenesis of human ADPKD. Furthermore they could serve as a useful resource for anti-fibrotic therapeutics.

Hypertension and renal function deterioration in black Africans with autosomal polycystic kidney disease

Background: High blood pressure (HBP) is a leading cause of end-stage renal disease (ESRD) in black African populations and it is frequently associated with autosomal polycystic kidney disease (ADPKD). We assessed the impact of HBP on progression of renal disease in black Africans with ADPKD. Objectives and Methods: We performed a retrospective study between 1995 and 2010 in nephrology out-patient clinic. ADPKD was diagnosed according to recent unified criteria add reference and seventh Joint National Committee classification was used for HBP definition. Statistical analyzes were performed with Stata 12 (Statacorp LP, TX, USA). Results: We included 71 patients (39 males and 32 females) with a mean age of 47±5 years. Prevalence of hypertension was 71.8% and it was present at diagnosis of ADPKD in 48 patients (67.6%). Median delay between HBP and ADPKD diagnosis was 25.6 months. Mean systolic/diastolic blood pressure was 168±30/96±16 mm Hg. After median follow-up of 1823 days, adjusted incidence rate of ESRD in hypertensive and normotensive patients was respectively 0.05 events/100,000 patient-years and 0.03 events/100,000 patient-years ( P =0.02). Anti-hypertensive therapy included angiotensin-converting-enzyme (ACE) inhibitors in 51% of patients, but less than 1/3 normalized their blood pressure. At univariate analysis, ESRD was correlated with age, gender, body mass index, HBP and proteinuria. Multiple logistic regression analysis identified age (odds ratio (OR)=1.14; P =0.06) and HBP (OR=1.67; P =0.02) as associated with ESRD. Conclusion: Hypertension with organ damage is frequent in black African patients with ADPKD. Age and HBP at diagnosis were the main factors associated with ESRD.

A New PKD-1 Mutation Discovered in a Black African Woman With Autosomal Polycystic Kidney Disease

Autosomal polycystic kidney disease (ADPKD) is a genetic disorder with two causal PKD-1 and PKD-2. Genetic studies have demonstrated an important allelic variability between patients but few data are known about genetic variants in African populations. We report a new mutation found in a 41-year old women with mild chronic kidney disease secondary to ADPKD. Molecular genetic testing found a deletion of 2 nucleotides A and C at positions 7290 and 7291 followed by insertion of a 5-base pair (CTGCA) located in exon 18 of the PKD1 gene. This newly identified frame shifting was compared to the PKD gene database but no similar mutation was yet reported. Other screened family members did not present any mutation.

Successful Renal Transplantation in Patients with Polycystic Kidneys after Renal Contraction by Renal Artery Embolization - Report on 2 Cases

,Autosomal polycystic kidney disease is responsible for about 10% of the cases of end stage renal disease. The increase in kidney size is usually proportional to the degree of deterioration in renal function. At the time of transplantation, these nonfunctional kidneys can be massively enlarged and nephrectomy is required before renal transplantation. However, pretransplantation nephrectomy of polycystic kidneys has the potential risk of surgical complications, including ileus, hernias, infection, excessive bleeding and/or intestinal injury. We report here on two cases successful renal transplantation in patients with polycystic kidneys after renal contraction by renal artery embolization and without nephrectomy. The volume reduction was evaluated by CT before and 3 months after renal artery embolization and the reduction in volume was 48% and 44 % in each case, respectively. The embolization was well tolerated in both cases without immediate or delayed complications except for fever and lumbar flank pain. Four months after renal artery embolization, both of the patients successfully received a transplant from living donors.

State-of-the art data normalization methods improve NMR-based metabolomic analysis

Extracting biomedical information from large metabolomic datasets by multivariate data analysis is of considerable complexity. Common challenges include among others screening for differentially produced metabolites, estimation of fold changes, and sample classification. Prior to these analysis steps, it is important to minimize contributions from unwanted biases and experimental variance. This is the goal of data preprocessing. In this work, different data normalization methods were compared systematically employing two different datasets generated by means of nuclear magnetic resonance (NMR) spectroscopy. To this end, two different types of normalization methods were used, one aiming to remove unwanted sample-to-sample variation while the other adjusts the variance of the different metabolites by variable scaling and variance stabilization methods. The impact of all methods tested on sample classification was evaluated on urinary NMR fingerprints obtained from healthy volunteers and patients suffering from autosomal polycystic kidney disease (ADPKD). Performance in terms of screening for differentially produced metabolites was investigated on a dataset following a Latin-square design, where varied amounts of 8 different metabolites were spiked into a human urine matrix while keeping the total spike-in amount constant. In addition, specific tests were conducted to systematically investigate the influence of the different preprocessing methods on the structure of the analyzed data. In conclusion, preprocessing methods originally developed for DNA microarray analysis, in particular, Quantile and Cubic-Spline Normalization, performed best in reducing bias, accurately detecting fold changes, and classifying samples.Electronic supplementary materialThe online version of this article (doi:10.1007/s11306-011-0350-z) contains supplementary material, which is available to authorized users.

Hypertension in Black Africans with Autosomal Polycystic Kidney Disease

Introduction: High blood pressure (HBP) that is a leading cause of end-stage renal disease (ESRD) in black African populations and is frequently associated to autosomal polycystic kidney disease (ADPKD). This study aimed to describe prevalence and severity of HBP in black Africans with ADPKD and to identify associated risk factors. Patients and methods: We performed a retrospective study of 65 ADPKD patients regularly followed in outpatient nephrology clinic between 1995 and 2009. ADPKD was diagnosed according to recent unified criteria (2009). Statistical analyses were done with SPSS 16.0. Results: We included 65 patients (36 males and 29 females) with a mean age of 47 ± 5 years. Hypertension was found in 73.8 % of patients and it preceded diagnosis of ADPKD in 23 patients (median delay of 28 months). Mean systolic/diastolic blood pressure was 168 ± 30 /96 ± 16 mm Hg respectively. All hypertensive patients presented retinopathy and left ventricular hypertrophy. Two patients presented stroke. Fifty one percent of patients were treated with angiotensin converting enzyme inhibitors alone and 29% received combinations of anti-hypertensive drugs. One third of them had their blood pressure normalized. Patients with HBP at diagnosis showed a similar proportion of ESRD in comparison with normotensive patients (p=0.12). At univariate analysis, HBP was correlated with age, gender, BMI, GFR and proteinuria. Multiple regression analysis identified age (OR=1.95, p=0.05) and glomerular filtration rate (OR=2.33, p=0.001) as independently associated to HBP. Conclusion: Hypertension with organ damage is frequent in Senegalese patients with ADPKD. Age and glomerular filtration rate at diagnosis were the main risk factors of HBP identified in our patients.

Embolization of Polycystic Kidneys as an Alternative to Nephrectomy Before Renal Transplantation: A Pilot Study

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.

AUTOSOMAL DOMINANT POLYCYSTIC KIDNEY DISEASE AND HYPERTENSION: PP.30.182

Objective: Autosomal polycystic kidney disease (APKD) is a common hereditary renal disease with an incidence of 1/1.000 people, it's associated with development of hypertension and chronic kidney disease (CKD), both important cardiovascular risk factors (CRF). We considered this study to see the relationship between hypertension, CRF and CKD in APKD. Methods: The study was conducted in the Guadalajara's Hospital during 2009. Recording was made for sex, weight, height, BMI, CRF, target organ damage (TOD) (myocardial infarction, heart failure, coronary ischemia, stroke and CKD (GFR < 60 ml/min/1, 73m2), comorbidity (Charlson Index). The statistical analysis was carried out by percentages, qualitative variables by chi square and quantitative by Student t test. A p value <0.05 was considered statistically significant. Results: There have been 56 patients with APKD, hypertension was confirmed in 32 (57.1%), 55.4% women, BMI was 27.02 ± 4.08, mean age was 52.82 ± 18.91 and CKD in 9 (16.1%), 16.1% had TOD. The presence of hypertension was related to age >55 years in males and >65 in women (p = 0.009), but there were no significant differences in other CRF such as dyslipidemia, smoking, impaired fasting glucose, dyslipidemia, obesity, diabetes mellitus or metabolic syndrome, although hypertensive patients had more CKD this was not significant (p = 0.063). On the other hand the risk of TOD (p = 0.036, OR: 7.6 [95% CI 0,88–66,2]), age (p:0.007, 95% CI −23.3 to −3.8) and Charlson I. (p = 0.0001, 95% CI −2.50 to −1.01) was higher in hypertensive patients. (Table 01 and 02).Conclusions: We note a high prevalence of hypertension in patients with APKD. The hypertension in patients with APKD is associated with the presence of TOD, more comorbidity and age, and it's important that eight of nine patients with CKD were hypertensive. Further studies should be conducted to determine the actual role of APKD in the presence of reno-cardiovascular damage, on the other side as there is no specific treatment for APKD, it's important an adequate control of hypertension.