Inositol 1,4,5-triphosphate receptor 3 promotes renal cyst development in autosomal dominant polycystic kidney disease / 生理学报

The purpose of the present study was to determine the role of inositol 1,4,5-trisphosphate receptor 3 (IP3R3) in renal cyst development in autosomal dominant polycystic kidney disease (ADPKD). 2-aminoethoxy-diphenyl borate (2-APB) and shRNA were used to suppress the expression of IP3R3. The effect of IP3R3 on cyst growth was investigated in Madin-Darby canine kidney (MDCK) cyst model, embryonic kidney cyst model and kidney specific Pkd1 knockout (PKD) mouse model. The underlying mechanism of IP3R3 in promoting renal cyst development was investigated by Western blot and immunofluorescence staining. The results showed that the expression level of IP3R3 was significantly increased in the kidneys of PKD mice. Inhibiting IP3R3 by 2-APB or shRNA significantly retarded cyst expansion in MDCK cyst model and embryonic kidney cyst model. Western blot and immunofluorescence staining results showed that hyperactivated cAMP-PKA signaling pathway in the growth process of ADPKD cyst promoted the expression of IP3R3, which was accompanied by a subcellular redistribution process in which IP3R3 was translocated from endoplasmic reticulum to intercellular junction. The abnormal expression and subcellular localization of IP3R3 further promoted cyst epithelial cell proliferation by activating MAPK and mTOR signaling pathways and accelerating cell cycle. These results suggest that the expression and subcellular distribution of IP3R3 are involved in promoting renal cyst development, which implies IP3R3 as a potential therapeutic target of ADPKD.

Aplicación tópica de ácido tranexámico en urología: ¿Una alternativa de manejo? / Topical Application of Tranexamic Acid in Urology: An Alternative Management?

Los agentes antifibrinolíticos, como el ácido tranexámico, por medio de su administración endovenosa se usan en distintos procedimientos quirúrgicos para prevenir la pérdida de sangrado perioperatorio.[1] Este medicamento es un derivado sintético análogo de la lisina que bloquea los sititos de unión de la lisina en el plasminógeno, inhibiendo su conversión a plasmina e interfiriendo en la fibrinólisis.[2] La aplicación del ácido tranexámico para disminuir el riesgo de sangrado ha sido utilizado en procedimientos urológicos como la resección transuretral prostática (RTUP), prostatectomía radical y nefrolitotomía percutánea (NLP),[3] [4] [5] también se emplea para disminuir las hematurias persistentes en pacientes con poliquistosis renal y en otras hematurias macroscópicas de origen urológico.

Antifibrinolytic agents, such as tranexamic acid, by intravenous administration are used in various surgical procedures to prevent perioperative bleeding loss.[1] This drug is a synthetic lysine analog derivative that blocks the lysine binding sites on plasminogen, inhibiting its conversion to plasmin and interfering with fibrinolysis.[2] The application of tranexamic acid to reduce the risk of bleeding has been used in urological procedures such as transurethral resection of the prostate (TURP), radical prostatectomy and nephrolithotomy. The application of tranexamic acid to reduce the risk of bleeding has been used in urological procedures such as transurethral resection of the prostate (TURP), radical prostatectomy and percutaneous nephrolithotomy (PNL),[3] [4] [5] it is also used to reduce persistent hematuria in patients with polycystic kidney disease and other macroscopic hematuria of urological origin.

Enlarged multicystic dysplastic kidneys with oligohydramnios during infancy caused by NPHP3 gene mutation / 中华医学遗传学杂志

OBJECTIVE@#To explore the clinical features and genomic abnorm ality of a fetus enlarged multicystic dysplastic kidneys with oligohydramnios caused by NPHP3 gene mutation.@*METHODS@#The fetuse was found to have multicystic dysplastic kidneys with oligohydramnios upon ultrasonography during the second trimester. Following induced abortion, fetal tissue was collected for the extraction of DNA, chromosomal microarray analysis (CMA) and whole exome sequencing (WES). Sanger sequencing was used to verify the suspected variants in the family.@*RESULTS@#Antenatal ultrasound examination at 19 weeks showed "polycystic" kidneys with Oligohydramnios. Delivery was by induced labour because of the critically low amniotic fluid volume. Testing of CMA was normal. WES showed a compound heterozygous mutation of c.1817G>A, p.W606X; c.432dupA, p.E145Rfs*18 mutations are novel mutations in this study.@*CONCLUSION@#The research may further expand the NPHP3 gene mutation spectrum. Enlarged multicystic dysplastic kidneys with oligohydramnios caused by NPHP3 gene mutation at least include one or two splice site mutation, frameshift mutation or nonsense mutation foetal poor prognosis.

Trastornos metabólicos urinarios en pacientes urolitiásicos con enfermedad renal poliquística y sin ella / Urinary metabolic disorders in urolithiasis patients with and without polycystic kidney disease

Introducción: La urolitiasis se ha incrementado en las últimas décadas. La enfermedad renal poliquística autosómica dominante (ERPAD), enfermedad renal hereditaria más frecuente, ocupa un lugar preponderante. Objetivos: Identificar la frecuencia de presentación de los trastornos metabólicos urinarios en pacientes litiásicos cubanos con ERPAD y sin ella Métodos: Estudio descriptivo, transversal. Fueron estudiados 579 pacientes adultos sin ERPAD, seleccionados por muestreo simple aleatorio y los 21 pacientes con ERPAD, del total de pacientes con litiasis urinaria que se realizó estudio metabólico renal en el Laboratorio de Fisiopatología Renal del Instituto de Nefrología, en el periodo 2010-2015. Los datos fueron tomados de la historia clínica y del informe de estudio metabólico renal. La información se procesó de forma automatizada (SPSS 22.0). Se utilizó el promedio, desviación estándar, análisis de distribución de frecuencias y el test de homogeneidad. Resultados: En los pacientes con ERPAD predominó el sexo femenino (57,1 por ciento), mientras que en los pacientes sin ERPAD, el masculino (63,4 por ciento). Los trastornos más frecuentes en la población no poliquística fueron hipercalciuria (45,3 por ciento) e hipofosfatemia (17,1 por ciento). En los poliquísticos, aclaramiento aumentado de ácido úrico (38,1 por ciento) e hipercalciuria (23,8 por ciento). Se encontraron diferencias estadísticamente significativas para aumento del aclaramiento de ácido úrico (p = 0,01) e hiperfosfatemia (p = 0,04). Conclusiones: Los principales trastornos metabólicos de los pacientes litiásicos, tanto poliquísticos como no poliquísticos, son el aclaramiento de ácido úrico aumentado, hipercalciuria, hiperuricosuria e hipofosfatemia, aunque el orden de presentación es diferente. El aclaramiento de ácido úrico aumentado y la hiperfosfatemia se presentan con mayor frecuencia en los pacientes litiásicos poliquísticos(AU)

Introduction: Urolithiasis has increased in recent decades. Autosomal dominant polycystic kidney disease (ADPKD), the most common of all hereditary kidney diseases, occupies a predominant position in terms of incidence. Objectives: Identify the frequency of occurrence of urinary metabolic disorders in Cuban urolithiasis patients with and without ADPKD. Methods: A descriptive cross-sectional study was conducted of 579 adult patients without ADPKD selected by simple random sampling, and 21 patients with ADPKD, from the total urolithiasis patients undergoing renal metabolic evaluation at the Renal Physiopathology Laboratory of the Institute of Nephrology in the period 2010-2015. Data were obtained from medical records and reports of renal metabolic studies. Information was processed with the statistical software SPSS version 22.0. Average and standard deviation were estimated and use was made of frequency distribution analysis and homogeneity testing. Results: A predominance was found of female sex among patients with ADPKD (57.1 percent) and male sex among patients without ADPKD (63.4 percent). The most common disorders were hypercalciuria (45.3 percent) and hypophosphatemia (17.1 percent) in the non-polycystic population, and increased uric acid clearance (38.1 percent) and hypercalciuria (23.8 percent) in polycystic patients. Statistically significant differences were found in uric acid clearance increase (p = 0.01) and hyperphosphatemia (p = 0.04). Conclusions: The main metabolic disorders of lithiasis patients, polycystic as well as non-polycystic, are increased uric acid clearance, hypercalciuria, hyperuricosuria and hypophosphatemia, with a varying order of presentation. Increased uric acid clearance and hyperphosphatemia are more common in polycystic lithiasis patients(AU)

Genetic testing and prenatal diagnosis for a Chinese pedigree affected with Meckel-Gruber syndrome / 中华医学遗传学杂志

OBJECTIVE@#To carry out genetic testing and prenatal diagnosis for a Chinese couple whom had conceived two fetuses featuring multiple malformations including polycystic kidney, polydactyly and encephalocele.@*METHODS@#Following elective abortion, the fetus from the second pregnancy was subjected to whole exome sequencing. Suspected pathogenic variants were verified by Sanger sequencing of the fetus and its parents.@*RESULTS@#The fetus was found to harbor compound heterozygous variants of the CEP290 gene, namely c.2743G>T (p.E915X) and c.2587-2A>T, which were respectively inherited from its father and mother. The same variants were not detected among 100 healthy controls nor reported previously. Bioinformatic analysis suggested both variants to be deleterious. The fetus was diagnosed with Meckel-Gruber syndrome. Prenatal diagnosis for the couple during their next pregnancy suggested that the fetus did not carry the above pathogenic variants.@*CONCLUSION@#The compound heterozygous variants of the CEP290 gene probably underlay the pathogenesis of Meckel-Gruber syndrome in the second fetus. Above finding has provided a basis for genetic counseling and prenatal diagnosis for the couple, and also enriched the mutational spectrum of the CEP290 gene.

Prenatal diagnosis and genetic counseling in two pedigrees affected with infantile polycystic kidney disease due to PKHD1 gene mutations / 中华医学遗传学杂志

OBJECTIVE@#To detect potential mutations of the PKHD1 gene in two pedigrees affected with infantile polycystic kidney disease.@*METHODS@#Clinical data and peripheral venous blood samples were collected from the probands and their parents as well as fetal amniotic fluid cells. Genome DNA was extracted from the peripheral blood samples and amniotic fluid cells. Exons 32 and 61 of the PKHD1 gene were amplified with PCR and subjected to direct sequencing.@*RESULTS@#The proband of pedigree 1 was found to carry c.4274T>G (p.Leu1425Arg) mutation in exon 32 and c.10445G>C (p.Arg3482Pro) mutation in exon 61 of the PKHD1 gene, which were inherited from her father and mother, respectively. The fetus has carried the c.4274T>G (p.Leu1425Arg) mutation. In pedigree 2, the wife and her husband had respectively carried a heterozygous c.5979_5981delTGG mutation and a c.9455delA mutation of the PKHD1 gene. No chromosomal aberration was found in the umbilical blood sample, but the genetic testing of their fetus was failed. Based on software prediction, all of the 4 mutations were predicted to be pathogenic.@*CONCLUSION@#PKHD1 c.4274T>G (p.Leu1425Arg), c.10445G>C (p.Arg3482Pro), c.5979_5981delTGG and c.9455delA were likely to be pathogenic mutations. The results have facilitated genetic counseling and prenatal diagnosis for the two pedigrees.

The role of calmodulin in regulating calcium-permeable PKD2L1 channel activity

Polycystic kidney disease 2-like-1 (PKD2L1), polycystin-L or transient receptor potential polycystin 3 (TRPP3) is a TRP superfamily member. It is a calcium-permeable non-selective cation channel that regulates intracellular calcium concentration and thereby calcium signaling. Although the calmodulin (CaM) inhibitor, calmidazolium, is an activator of the PKD2L1 channel, the activating mechanism remains unclear. The purpose of this study is to clarify whether CaM takes part in the regulation of the PKD2L1 channel, and if so, how. With patch clamp techniques, we observed the current amplitudes of PKD2L1 significantly reduced when coexpressed with CaM and CaMΔN. This result suggests that the N-lobe of CaM carries a more crucial role in regulating PKD2L1 and guides us into our next question on the different functions of two lobes of CaM. We also identified the predicted CaM binding site, and generated deletion and truncation mutants. The mutants showed significant reduction in currents losing PKD2L1 current-voltage curve, suggesting that the C-terminal region from 590 to 600 is crucial for maintaining the functionality of the PKD2L1 channel. With PKD2L1608Stop mutant showing increased current amplitudes, we further examined the functional importance of EF-hand domain. Along with co-expression of CaM, ΔEF-hand mutant also showed significant changes in current amplitudes and potentiation time. Our findings suggest that there is a constitutive inhibition of EF-hand and binding of CaM C-lobe on the channel in low calcium concentration. At higher calcium concentration, calcium ions occupy the N-lobe as well as the EF-hand domain, allowing the two to compete to bind to the channel.

Fibrose hepática congênita e venopatia portal obliterativa sem hipertensão portal - revisão da literatura com base em um caso assintomático / Congenital hepatic fibrosis and obliterative portal venopathy without portal hypertension - a review of literature based on an asymptomatic case

ABSTRACT The disease and the case reported here are relevant especially because of their varied clinical presentation, possibility of being associated with other disorders affecting several organs and possible differential diagnoses. Congenital Hepatic Fibrosis is an autosomal recessive disease due to mutation in the PKHD1 gene, which encodes the fibrocystin/polyductine protein. It is a cholangiopathy, characterized by varying degrees of periportal fibrosis and irregular proliferation of bile ducts. Affected patients are typically diagnosed in childhood, but in some cases the disease may remain asymptomatic for many years. The exact prevalence and incidence of the disease are not known, but it is consider a rare disease, with a few hundred cases described worldwide. It can affect all ethnic groups and occur associated with various hereditary and non-hereditary disorders. The clinical presentation is quite variable, with melena and hematemesis being initial symptoms in 30%-70% of the cases. More rarely, they may present episodes of cholangitis. The disease has been classified into four types: portal hypertension, cholestasis / cholangitis, mixed and latent. Diagnosis begins with imaging tests, but the definition is made by the histopathological sample. So far, there is no specific therapy that can stop or reverse the pathological process. Currently, the therapeutic strategy is to treat the complications of the disease.

RESUMO A patologia e o caso aqui reportados são relevantes especialmente devido sua variada apresentação clínica, possibilidade de estar associada com outras desordens acometendo diversos órgãos e pelos possíveis diagnósticos diferenciais. A fibrose hepática congênita é uma doença autossômica recessiva, devido mutação no gene PKHD1, que codifica a proteína fibrocistina/poliductina. É uma colangiopatia, caracterizada por variados graus de fibrose periportal e proliferação irregular de ductos biliares. Os pacientes acometidos são tipicamente diagnosticados na infância, mas em alguns casos a doença pode permanecer assintomática por muitos anos. Exatas prevalência e incidência da doença não são conhecidas, mas sabe-se que é uma doença bastante rara, com algumas centenas de casos descritos no mundo. Pode afetar todos grupos étnicos e ocorrer associada com diversas desordens hereditárias e não-hereditárias. A apresentação clínica é bastante variável, com melena e hematêmese sendo sintomas iniciais em 30%-70% dos casos. Mais raramente, podem apresentar episódios de colangite. A doença tem sido classificada em quatro tipos: hipertensão portal, colestática/colangite, mista e latente. O diagnóstico inicia com exames de imagem, mas a definição é feita pela amostra histopatológica. Até o momento, não há terapia específica que possa parar ou reverter o processo patológico e a estratégia terapêutica atual é tratar as complicações da doença.

Quistes gigantes en la poliquistosis renal. Un indicador poco frecuente de nefrectomía / Giant polycystic kidney. A rare indication for nephrectomy

A 49-year-old male patient was diagnosed with ADPKD while the evaluation of urinary tract infection in 2010. He was suffering from nutritional problems due to gastro-intestinal disturbances and vomiting secondary to the pressure of the kidneys. He was also a candidate for kidney transplantation, but there was no adequate and enough space in the abdomen for the transplant kidney. Therefore, we performed open unilateral nephrectomy to the bigger kidney. As we now there is not too many cases regarding giant polycystic kidney nephrectomy, we presented our case to make additional contribution to the current literature

Se diagnosticó poliquistosis renal autosómica dominante a un paciente masculino de 49 años durante la evaluación de un cuadro de infección urinaria en 2010. El paciente padecía problemas nutricionales debido a trastornos gastrointestinales y vómitos causados por la presión de los riñones. Asimismo, era candidato a trasplante renal, pero el espacio del abdomen no era adecuado ni suficiente para realizar este procedimiento. Por lo tanto se realizó una nefrectomía unilateral, en el riñón de mayor tamaño. Debido a que no se conocen muchos casos de nefrectomía en pacientes con poliquistosis renal con quistes gigantes, presentamos este para realizar un aporte a la bibliografía existente

Basiliximab-Induced Non-Cardiogenic Pulmonary Edema in a Kidney Transplant Patient / 대한이식학회지

Induction therapy with basiliximab is widely administered after kidney transplantation to prevent acute rejection. Herein, we report a case of non-cardiogenic pulmonary edema induced by basiliximab. To the best of our knowledge, such case has not been reported to date in Korea. A 54-year-old man with polycystic kidney disease received kidney transplantation. As induction therapy, he was prescribed basiliximab. On day 4, the second dose of basiliximab was administered. The patient complained of acute hypoxia 23 hours later, which led to circulatory collapse. He was discharged 3 weeks later with stable renal function. Pulmonary edema was presumed to have been caused by increased pulmonary capillary permeability. A possible hypothesis for this event occurring after the second basiliximab injection is steroid-related effects. Non-cardiogenic pulmonary edema is a complication that might occur after basiliximab induction therapy. Physicians should be aware of this potentially life-threatening complication.

Femoral Neuropathy Secondary to Autosomal Dominant Polycystic Kidney Disease: A Case Report

Compressive femoral neuropathy is a disabling condition accompanied by difficulty in hip flexion and knee extension. It may result from retroperitoneal hematoma or bleeding, or from complications associated with pelvic, hip surgery, and renal transplants. A 55-year-old female with autosomal dominant polycystic kidney disease presented with proximal muscle weakness in lower extremities. The patient experienced recurrent renal cyst infection, with aggravated weakness during each event. Electromyography and nerve conduction study revealed bilateral femoral neuropathy. Computed tomography and magnetic resonance images were added to further identify the cause. As a result, a diagnosis of femoral neuropathy caused by enlarged polycystic kidney was made. Cyst infection was managed with antibiotics. Renal function was maintained by frequent regular hemodialysis. While avoiding activities that may increase abdominal pressure, rehabilitation exercises were provided. Motor strength in hip flexion and knee extension improved, and was confirmed via electrodiagnostic studies.

Incidental Detection of Peri-Renal Hemorrhage on F-18 FDG PET/CT Imaging in a Patient with Polycystic Kidney Disease / 대한핵의학회잡지

A 72-year-old male patient with a history of polycystic kidney disease and lung malignancy underwent F-18 fluorodeoxyglucose positron emission tomography/computed tomography (FDG PET/CT) for the evaluation of tumor recurrence. The FDG PET/CT and subsequent non-enhanced CT scans revealed a hemorrhage in the peri-renal space of the left original kidney. Interesting in this case was the incidental detection of unexpected peri-renal hemorrhage during an oncologic assessment with FDG PET/CT.

Autosomal Dominant Polycystic Kidney Desease Coexisting with Renal Dysplasia. First Case Described and Followed Since Prenatal Period

Autosomal dominant polycystic kidney disease (ADPKD) is the most frequent hereditary renal disease and causes terminal chronic renal failure. ADPKD is characterized by bilateral multiple renal cysts, which are produced by mutations of the PKD1 and PKD2 genes. PKD1 is located on chromosome 16 and encodes a protein that is involved in cell cycle regulation and intracellular calcium transport in epithelial cells and is responsible for 85% of ADPKD cases. Although nine cases of unilateral ADPKD with contralateral kidney agenesis have been reported, there have been no reports of early childhood ADPKD. Here, we report the only case of unilateral ADPKD with contralateral kidney dysplasia in the world in a four year-old girl who was intrauterinely diagnosed since she was 20 weeks old and followed for four years until present.

Pyonephrosis caused by Salmonella sp. in a patient with polycystic kidney disease undergoing hemodialysis / Pionefrose causada por Salmonella sp. em um paciente com doença renal policística submetido a hemodiálise

AIMS: This article reports a case of pyonephrosis caused by Salmonella sp. in a patient with polycystic kidney disease undergoing hemodialysis treatment. CASE DESCRIPTION: An elderly male patient previously diagnosed with polycystic kidney disease undergoing standard hemodyalitic treatment presented uronephrosis, evolving to pyonephrosis caused by Salmonella sp., and was successfully treated with ciprofloxacin. CONCLUSIONS: The polycystic kidney disease may have contributed to the bacteria's attachment to the kidney, due to increase of permeability of the intestinal mucosa, easier bacterial translocation to bloodstream and its subsequent accommodation in the infected organ.

OBJETIVOS: Este artigo relata um caso de pionefrose causada por Salmonella sp. em paciente com doença renal policística em tratamento por hemodiálise. DESCRIÇÃO DO CASO: Um paciente idoso do sexo masculino, previamente diagnosticado com doença renal policística, em tratamento convencional por hemodiálise, apresentou uronefrose, evoluindo a pionefrose causada por Salmonella sp., sendo tratado com sucesso com ciprofloxacino. CONCLUSÕES: A doença renal policística pode ter contribuído para a instalação da bactéria no rim, visto o aumento da permeabilidade da mucosa intestinal e maior facilidade de translocação da bactéria para a corrente sanguínea e seu posterior alojamento no órgão infectado.

Baseline General Characteristics of the Korean Chronic Kidney Disease: Report from the KoreaN Cohort Study for Outcomes in Patients With Chronic Kidney Disease (KNOW-CKD)

The KoreaN Cohort Study for Outcomes in Patients With Chronic Kidney Disease (KNOW-CKD) was developed to investigate various clinical courses and risk factors for progression of Korean chronic kidney disease (CKD). The KNOW-CKD study consists of nine clinical centers in Korea, and patients aged between 20 and 75 years with CKD from stage 1 to 5 (predialysis) were recruited. At baseline, blood and urine samples were obtained and demographic data including comorbidities, drugs, quality of life, and health behaviors were collected. Estimated glomerular filtration rate (eGFR) was calculated by 4-variable Modification of Diet in Renal Disease (MDRD) equation using isotope dilution mass spectrometry (IDMS)-calibrated serum creatinine measured at a central laboratory. As a dynamic cohort, a total of 2,341 patients were enrolled during the enrollment period from 2011 until 2015, among whom 2,238 subjects were finally analyzed for baseline profiles. The mean age of the cohort was 53.7 ± 12.2 year and 61.2% were men. Mean eGFR was 50.5 ± 30.3 mL/min/1.73 m². The participants with lower eGFR had a tendency to be older, with more comorbidities, to have higher systolic blood pressure (BP) and pulse pressure, with lower income level and education attainment. The patients categorized as glomerulonephritis (GN) were 36.2% followed by diabetic nephropathy (DN, 23.2%), hypertensive nephropathy (HTN, 18.3%), polycystic kidney disease (PKD, 16.3%), and other unclassified disease (6.1%). The KNOW-CKD participants will be longitudinally followed for 10 years. The study will provide better understanding for physicians regarding clinical outcomes, especially renal and cardiovascular outcomes in CKD patients.

Baseline Cardiovascular Characteristics of Adult Patients with Chronic Kidney Disease from the KoreaN Cohort Study for Outcomes in Patients With Chronic Kidney Disease (KNOW-CKD)

Cardiovascular disease (CVD) is the most common cause of death in patients with chronic kidney disease (CKD). We report the baseline cardiovascular characteristics of 2,238 participants by using the data of the KoreaN Cohort Study for Outcomes in Patients With Chronic Kidney Disease (KNOW-CKD) study. The cohort comprises 5 subcohorts according to the cause of CKD: glomerulonephritis (GN), diabetic nephropathy (DN), hypertensive nephropathy (HTN), polycystic kidney disease (PKD), and unclassified. The average estimated glomerular filtration rate (eGFR) was 50.5 ± 30.3 mL/min⁻¹/1.73 m⁻² and lowest in the DN subcohort. The overall prevalence of previous CVD was 14.4% in all patients, and was highest in the DN followed by that in the HTN subcohort. The DN subcohort had more adverse cardiovascular risk profiles (higher systolic blood pressure [SBP], and higher levels of cardiac troponin T, left ventricular mass index [LVMI], coronary calcium score, and brachial-ankle pulse wave velocity [baPWV]) than the other subcohorts. The HTN subcohort exhibited less severe cardiovascular risk profiles than the DN subcohort, but had more severe cardiovascular risk features than the GN and PKD subcohorts. All these cardiovascular risk profiles were inversely correlated with eGFR. In conclusion, this study shows that the KNOW-CKD cohort exhibits high cardiovascular burden, as other CKD cohorts in previous studies. Among the subcohorts, the DN subcohort had the highest risk for CVD. The ongoing long-term follow-up study up to 10 years will further delineate cardiovascular characteristics and outcomes of each subcohort exposed to different risk profiles.

Focal segmental glomerulosclerosis in atypical polycystic kidney disease

No abstract available.

Mitogen-activated Protein Kinases in the Development of Normal and Diseased Kidneys

Mitogen-activated protein kinases (MAPKs) play important roles in various cellular functions including proliferation, differentiation, and apoptosis. We showed that MAPKs are developmentally regulated in the rat kidney. p38 MAPK (p38) and extracellular signal-regulated kinase (ERK) were strongly expressed in the fetal kidney, whereas c-Jun N-terminal kinase (JNK) was detected predominantly in the adult kidney. The inhibition of p38 or ERK in organ culture resulted in reduced nephron formation with or without reduced kidney size. On the other hand, persistent fetal expression pattern of MAPKs, i.e., upregulation of p38 and ERK and downregulation of JNK, was observed in the cyst epithelium of human renal dysplasia, ovine fetal obstructive uropathy, and pcy mice, a model of polycystic kidney disease. Furthermore, activated p38 and ERK induced by cyclic stretch mediated proliferation and TGF-β1 expression in ureteric bud cells, probably leading to cyst formation and dysplastic changes. Inhibition of ERK slowed the disease progression in pcy mice. Finally, ERK and p38 were inactivated in the early embryonic kidney subjected to maternal nutrient restriction, characterized by reduced ureteric branching and nephron number. Thus, MAPKs mediate the development of normal and diseased kidney. Their modulation may result in novel therapeutic strategies against developmental abnormalities of the kidney.