Autosomal dominant polycystic kidney disease (ADPKD) is the most common hereditary renal disease. There are some reports in the literature concerning unilateral ADPKD. However, in adults, only a few cases of unilateral ADPKD with agenesis of contralateral kidney have been reported. We present a case of unilateral ADPKD with agenesis of contralateral kidney in a 66-yr-old man. Radiographic images showed the enlarged right kidney with multiple variable-sized cysts and the absence of the left kidney. The diagnosis of ADPKD was confirmed by the family screening. The patient received maintenance hemodialysis for endstage renal disease. We report a case of unilateral ADPKD associated with contralateral renal agenesis in a 66-yr-old male patient with a literature review.
Abdomen/pathology ; Aged ; Female ; Human ; Kidney/abnormalities* ; Male ; Pedigree ; Polycystic Kidney, Autosomal Dominant/diagnosis* ; Polycystic Kidney, Autosomal Dominant/pathology* ; Polycystic Kidney, Autosomal Dominant/physiopathology ; Radiopharmaceuticals/metabolism ; Technetium Tc 99m Dimercaptosuccinic Acid/metabolism

Autosomal dominant polycystic kidney disease (ADPKD) is the most common hereditary kidney disease. It is characterized by the dysregulated growth of kidney cysts, resulting in end-stage kidney failure. By identifying the genes involved in ADPKD and detailing the molecular pathology of the disease, putative therapeutic agents have been developed. However, clinical trials of vasopressin receptor antagonists and somatostatin analogues have raised several concerns among researchers and clinicians. Questions regarding when and who to treat and what surrogate marker to use for describing endpoints have been raised. This review focuses on the current methods for managing ADPKD and describes recent findings from clinical trials. The main difficulties associated with implementing therapeutic agents in patients with ADPKD and considerations for clinical settings will also be discussed.
Biomarkers ; Humans ; Hypertension ; Kidney ; Kidney Diseases ; Pathology, Molecular ; Polycystic Kidney Diseases ; Polycystic Kidney, Autosomal Dominant* ; Receptors, Vasopressin ; Renal Insufficiency ; Renal Insufficiency, Chronic ; Somatostatin

Autosomal dominant polycystic kidney disease (ADPKD) is a most common inherited renal disease, about 50% with a family history, although the exact etiology not yet clear. To date, ADPKD, a multisystem disorder without effective preventive and therapeutic means, has been shown to be detrimental to human health. Recent studies show that severe oligoasthenozoospermia, necrospermia, immotile sperm, azoospermia, epididymal cyst, seminal vesicle cyst, and ejaculatory duct cyst found in male ADPKD patients may lead to male infertility, though the specific mechanisms remain unknown. Structural anomaly of spermatozoa, defect of polycystin, mutation of PKD genes, and micro-deletion of the AZF gene could be the reasons for the higher incidence of abnormal semen quality in male ADPKD patients. Assisted reproductive techniques can increase the chances of pregnancy, whereas the health of the offspring should be taken into consideration. This article presents an overview of reproductive issues concerning infertile male ADPKD patients from the perspective of the morbidity, pathophysiological mechanism, diagnosis, and management of the disease.
Cysts ; pathology ; Ejaculatory Ducts ; pathology ; Female ; Humans ; Infertility, Male ; physiopathology ; Kidney ; pathology ; Male ; Mutation ; Polycystic Kidney, Autosomal Dominant ; physiopathology ; Pregnancy ; Reproductive Techniques, Assisted ; Semen Analysis ; Spermatozoa ; pathology

PURPOSE: Recent studies have showed that epithelial-mesenchymal transition (EMT) is a key process of glomerular and tubulointerstitial pathology in many chronic kidney diseases. However, there are no data of EMT in humane autosomal dominant polycystic kidney disease (ADPKD). PATIENTS AND METHODS: ADPKD kidneys (N = 5) with end stage renal disease (ESRD) and control kidneys (N = 4) were analyzed immnunohistochemically. We evaluated alpha-SMA, E-cadherin, vimentin, TGF-beta1 and Smad 2/3 expression in ADPKD and compared them with those in control kidney. These immunohistochemical findings were quantitatively analyzed by computer-assisted image analyzer and positive tubules (%). RESULTS: There were severe interstitial fibrosis and proliferation of alpha-SMA+ myofibroblasts in ADPKD. Cystic tubular epithelial cells in ADPKD lost epithelial marker (E-cadherin) and expressed mesenchymal markers (alpha-SMA, vimentin). There were significant increases of alpha-SMA (34.3 +/- 11.7% vs 0.9 +/- 1.5%), vimentin (19.9 +/- 3.9% vs 3.3 +/- 1.4%), TGF-beta1 (5.42 +/- 2.83% vs 0%) and Smad 2/3 (3.4 +/- 1.7% vs 0.7 +/- 0.6%) in ADPKD kidneys compared with control kidneys evidenced by computer-assisted image analyzer. When we analyze the positive tubules (%), the results were the same as computer-assisted image analyzer. CONCLUSION: Our results showed that the end stage of ADPKD is associated with TGF-beta, Smad 2/3 and markers of EMT. It suggests that TGF-beta mediated EMT has a role in progression of ADPKD.
Aged ; Biological Markers/metabolism ; Cell Division ; Disease Progression ; Epithelial Cells/*pathology ; Female ; Fibrosis ; Humans ; Kidney Glomerulus/pathology ; Kidney Tubules/pathology ; Male ; Mesoderm/*pathology ; Middle Aged ; Polycystic Kidney, Autosomal Dominant/*metabolism/*pathology ; Transforming Growth Factor beta/*metabolism

OBJECTIVETo investigate the expression and function of PKD1 and PKD2 in different kidney tissues and cell lines.

METHODSImmunoprecipitation, Western blotting, In situ hybridization and immunohistochemical staining methods were used to observe the expression of PKD1 mRNA and PKD2 mRNA and their protein abundance in different kidney tissues and cell lines.

RESULTSCoordinate expressions of PKD1 and PKD2 were found in all kidney tissues and cell lines. Distribution of PKD1 mRNA and PKD2 mRNA and their protein polycystin-1 and polycystin-2 in normal human adult kidney tissue were mainly expressed in the medullary collecting ducts and distal tubules. Positive staining was also found in the majority of cyst-lining epithelial cells of PKD1 cystic kidney tissue, PKD1 cyst-lining epithelia cell line and LLC-PK1. The expression level of them in cystic epithelia of ADPKD kidney tissue was much higher than that in adult renal tubules (P < 0.01).

CONCLUSIONSSimilar expression pattern of PKD1 and PKD2 and their different tissue distribution in different kidney tissues show that the molecular mutuality of PC-1 and PC-2 might be the base of their functional correlation. Polycystins might play an important role in the maintenance of tubular architecture.

Adult ; Animals ; Cell Line ; Gene Expression ; Humans ; Kidney ; metabolism ; Kidney Tubules, Collecting ; metabolism ; Kidney Tubules, Distal ; metabolism ; Kidney Tubules, Proximal ; cytology ; Polycystic Kidney, Autosomal Dominant ; pathology ; RNA, Messenger ; biosynthesis ; genetics ; Swine ; TRPP Cation Channels ; metabolism

Adolescent ; Child ; Child, Preschool ; DNA Mutational Analysis ; Diagnosis, Differential ; Humans ; Infant ; Infant, Newborn ; Liver Diseases ; diagnosis ; genetics ; pathology ; Lung Diseases ; diagnosis ; genetics ; pathology ; Magnetic Resonance Imaging ; Mutation ; Polycystic Kidney, Autosomal Dominant ; diagnosis ; genetics ; pathology ; Polycystic Kidney, Autosomal Recessive ; diagnosis ; genetics ; pathology ; Prenatal Diagnosis ; Receptors, Cell Surface ; genetics ; Tomography, X-Ray Computed

The mutation of the PKD1 gene causes autosomal dominant polycystic kidney disease (ADPKD), and the PKD1 gene encodes polycystin-1 (PC-1). PC-1 is thought to be a cell-cell/matrix adhesion receptor molecule at the cell surface that is widely expressed in the kidney. However, there are controversies about the role of PC-1 protein and its expression when using different antibodies to detect it. We used two PC-1 antibodies; C-20 (Santa Cruz, sc-10372) as the C-terminal antibody, and P-15 (Santa Cruz, sc-10307) as the N-terminal antibody. We evaluated the PC-1 expression by performing immunoblotting on the human embryonic kidney (HEK) 293 cells and the renal proximal tubular epithelial cell (RPTEC) lysates. We characterized the expression of PC-1 in the fetal, adult and polycystic kidneys tissues by performing immunohistochemistry. We confirmed the PC-1 expression in the HEK 293 cells and the RPTEC lysates, but the expression was very low. The PC-1 proteins were diffusely expressed in the tubular epithelial cells cytoplasm in the fetal and adult kidneys, and the PC-1 expression was more prominent in the proximal tubules of the fetal kidney. In the ADPKD kidney, the PC-1 proteins were heterogenously and weakly expressed in the tubular or cyst lining epithelial cells. Our data suggests that the development of the kidney may regulate the expression of PC-1, and an altered PC-1 expression may contribute to cyst formation in ADPKD.
TRPP Cation Channels/chemistry/*metabolism ; Protein Structure, Tertiary ; Polycystic Kidney, Autosomal Dominant/*metabolism ; Middle Aged ; Male ; Kidney/*embryology/metabolism/*pathology ; Immunohistochemistry ; Humans ; *Gene Expression Regulation, Developmental ; *Gene Expression Regulation ; Cytoplasm/metabolism ; Cell Line

Polycystic liver is the most common extra-renal manifestation associated with autosomal dominant polycystic kidney disease (ADPKD), comprising up to 80% of all features. Patients with polycystic liver often suffer from abdominal discomfort, dyspepsia, or dyspnea; however, there have been few ways to relieve their symptoms effectively and safely. Therefore, we tried transcatheter arterial embolization (TAE), which has been used in treating hepatocellular carcinoma. We enrolled four patients with ADPKD in Seoul National University Hospital, suffering from enlarged polycystic liver. We embolized the hepatic arteries supplying the dominant hepatic segments replaced by cysts using polyvinyl alcohol particles and micro-coils. The patients were evaluated 12 months after embolization for the change in both liver and cyst volumes. Among four patients, one patient was lost in follow up and 3 patients were included in the analysis. Both liver (33%; 10%) and cyst volume (47.7%; 11.4%) substantially decreased in two patients. Common adverse events were fever, epigastric pain, nausea, and vomiting. We suggest that TAE is effective and safe in treating symptomatic polycystic liver in selected ADPKD patients.
Aged ; Catheterization ; Cysts/*therapy ; Embolization, Therapeutic/instrumentation/*methods ; Female ; Hepatic Artery ; Humans ; Liver/pathology/physiology ; Liver Diseases/pathology/*therapy ; Middle Aged ; Polycystic Kidney, Autosomal Dominant/diagnosis/*therapy ; Polyvinyl Alcohol/therapeutic use ; Tomography, X-Ray Computed