• Electrolytes & blood pressure
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• v.16 no.2
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• pp.23-26
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• 2018

A 22-year-old male patient was diagnosed with autosomal dominant polycystic kidney disease (ADPKD). He received conservative treatment with an angiotensin-converting enzyme inhibitor. Two years later, oral therapy, consisting of 60 mg tolvaptan per day, was initiated. Compared with height-adjusted total kidney volume, the rate of kidney growth reduced significantly from 7.33% to 0.66% annually, since commencement of the tolvaptan therapy. The liver enzyme profile and serum sodium level and osmolality were constantly within normal ranges. In Korea, this is the first reported case of a patient with ADPKD who received tolvaptan treatment for more than 1 year. This case demonstrates that long-term tolvaptan treatment appears to be safe, well tolerated, and effective for ADPKD.

• Journal of Genetic Medicine
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• v.13 no.1
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• pp.36-40
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• 2016

Tuberous sclerosis complex (TSC, MIM#191100) is an autosomal dominant neurocutaneous syndrome caused by mutation or deletion of TSC1 encoding hamartin or TSC2 encoding tuberin and characterized by seizure, mental retardation, and multiple hamartomas or benign tumors in the skin, brain, retina, heart, kidney, and lungs. The TSC2 gene on chromosome 16p13.3 lies adjacent to the PKD1 gene which is responsible for autosomal dominant polycystic kidney disease (MIM#173900). The TSC2/PKD1 contiguous gene syndrome (TSC2/PKD1 CGDS, MIM#600273) is caused by deletion of both TSC2 and PKD1 gene. We recently experienced a 15 month-old boy and a 26 month-old girl with TSC2/PKD1 CGDS confirmed by multiplex ligation-dependent probe amplification (MLPA) analysis. They showed not only typical neurologic manifestations of TSC such as epilepsy, subependymal nodules, and subcortical tubers, but also polycystic kidney disease. The contiguous gene syndrome involving PKD1 and TSC2 should be suspected in children with enlarged polycystic kidneys and TSC. MLPA analysis is a useful method for the genetic confirmation of TSC2/PKD1 CGDS.

• Biomolecules & Therapeutics
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• v.32 no.3
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• pp.291-300
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• 2024

Autosomal dominant polycystic kidney disease (ADPKD), a congenital genetic disorder, is a notable contributor to the prevalence of chronic kidney disease worldwide. Despite the absence of a complete cure, ongoing research aims for early diagnosis and treatment. Although agents such as tolvaptan and mTOR inhibitors have been utilized, their effectiveness in managing the disease during its initial phase has certain limitations. This review aimed to explore new targets for the early diagnosis and treatment of ADPKD, considering ongoing developments. We particularly focus on cell polarity, which is a key factor that influences the process and pace of cyst formation. In addition, we aimed to identify agents or treatments that can prevent or impede the progression of renal fibrosis, ultimately slowing its trajectory toward end-stage renal disease. Recent advances in slowing ADPKD progression have been examined, and potential therapeutic approaches targeting multiple pathways have been introduced. This comprehensive review discusses innovative strategies to address the challenges of ADPKD and provides valuable insights into potential avenues for its prevention and treatment.

• Journal of Veterinary Clinics
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• v.31 no.5
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• pp.466-468
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• 2014

Polycystic kidney disease (PKD) is characterized by multiple cysts within the renal parenchyma and is a common heritable disease in humans, dogs, and cats. However, a few cases of PKD have been described in captive pygmy hippopotamuses. Bilateral PKD was observed in a 33-year-old, 198-kg female pygmy hippopotamus during its necropsy in Seoul Zoo on 15 January 2013. The diagnosis of PKD was confirmed by gross findings and histopathological examination. One kidney was slightly enlarged, and the lower portion of other kidney contained a large cyst filled with light yellow, watery fluid. Both kidneys had numerous, variably sized fluid-filled cysts of 2 to 20 mm in diameter. Considerable portions of the renal cortex and medulla were replaced by cysts. Microscopic inspection showed that the cysts were lined with low cuboidal to flat epithelial cells. The present case report of PKD in a pygmy hippopotamus is the first in Korea.

• Clinical and Experimental Reproductive Medicine
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• v.49 no.4
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• pp.239-247
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• 2022

Objective: Asafoetida is a gum derived from Ferula assa-foetida, which is used in traditional Iranian medicine to treat some reproductive system disorders. The effects of asafoetida on ovarian tissue, expression of certain genes associated with polycystic ovary syndrome (PCOS), and levels of liver, kidney, and blood cell factors after treatment in a rat model were investigated. Methods: Thirty rats were divided into five groups: normal, polycystic, and treatment with three doses of asafoetida (12.5, 25, and 50 mg/kg for 3 weeks after PCOS induction). PCOS was induced by letrozole at a dose of 1 mg/kg administered orally for 3 weeks. Blood samples were taken, and the ovaries were removed and prepared for histomorphometric examination. Liver and kidney parameters were measured. The mRNA expression levels of luteinizing hormone receptor, CYP11A1, adenosine monophosphate-activated protein kinase, adiponectin, and adiponectin receptors 1 and 2 were also measured by real-time polymerase chain reaction. Results: The levels of liver, kidney, and blood parameters did not significantly differ between the treatment groups and the control group. At doses of 25 and 50 mg/kg, ovarian histopathology, especially the thicknesses of the theca and granulosa layers, was significantly improved relative to the PCOS group. The expression of target genes also improved in the 25 and 50 mg/kg treatment groups. Conclusion: Asafoetida can be used to treat PCOS as a complementary approach to conventional therapies. Asafoetida appears to act by regulating and activating metabolic and ovarian cycle enzymes.

• Journal of Veterinary Clinics
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• v.18 no.1
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• pp.70-73
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• 2001

Five-month-old a female mongrel puppy weighing 3.5 kg showed no systemic disorder and particular discomfort except abdominal distension at the first visit. On physical examination an irregular abdominal mass was palpated. One month later she was clumsy and uncoordinated. In addition, lethargy and anorexia were appeared. Then she became comatose and died in spite of initial therapy. In radiographic examination enlargement of both sides of kidney was observed. The hematological examination the dog had WBC of 16,250/$\mu$l, RBC of $7.2{\times}10^6$ $\mu$l, PCV of 32%, total protein of 8.0 g/dl, and fibrinogen of 900 mg/dl. In serum chemistry BUN was 87.4 mg/dl and creatinine was 5.1 mg/dl. Urinalysis revealed pH of 5.6, SG of 1.009 and protein of 500 mg/dl. In urine sediment test many RBCs, leukocytes, inflammatory cells and a few epithelial cells were observed. On histopathologic examination the size of right and left kidney were 15 cm, 16 cm in length, 6 cm, 6 cm in widths, respectively. Both sides of kidney were filled with brown-orange fluid and had irregular capsular surface. The cysts of various sizes were located throughout the cortex and medulla. No abnormality was found in any other organs. Histologically, cyst was lined by cuboidal to slightly flattened tubular epithelium and surrounded by mature fibrous connective tissue. Glomeruli, tubule and renal pelvis remained normal between cysts and exfoliated epithelial cells.

• BMB Reports
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• v.40 no.4
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• pp.467-474
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• 2007

Autosomal recessive polycystic kidney disease (ARPKD) is one of the important genetic disorders in pediatric practice. Mutation of the polycystic kidney and hepatic disease gene 1 (PKHD1) was identified as the cause of ARPKD. The gene encodes a 67-exon transcript for a large protein of 4074 amino acids termed fibrocystin, but its function remains unknown. The neoplastic-like in cystic epithelial proliferation and the epidermal growth factor/epidermal growth factor receptor (EGF/EGFR) axis overactivity are known as the most important characteristics of ARPKD. Since the misregulation of $Ca^{2+}$ signaling may lead to aberrant structure and function of the collecting ducts in kidney of rat with ARPKD, present study aimed to investigate the further mechanisms of abnormal proliferation of cystic cells by inhibition of PKHD1 expression. For this, a stable PKHD1-silenced HEK-293T cell line was established. Then cell proliferation rates, intracellular $Ca^{2+}$ concentration and extracellular signal-regulated kinase 1/2 (ERK1/2) activity were assessed after treatment with EGF, a calcium channel blocker and agonist, verapamil and Bay K8644. It was found that PKHD1-silenced HEK-293T cell lines were hyperproliferative to EGF stimulation. Also PKHD1-silencing lowered the intracellular $Ca^{2+}$ and caused EGF-induced ERK1/2 overactivation in the cells. An increase of intracellular $Ca^{2+}$ in PKHD1-silenced cells repressed the EGF-dependent ERK1/2 activation and the hyperproliferative response to EGF stimulation. Thus, inhibition of PKHD1 can cause EGF-induced excessive proliferation through decreasing intracellular $Ca^{2+}$ resulting in EGF-induced ERK1/2 activation. Our results suggest that the loss of fibrocystin may lead to abnormal proliferation in kidney epithelial cells and cyst formation in ARPKD by modulation of intracellular $Ca^{2+}$.

• Genomics & Informatics
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• v.10 no.1
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• pp.16-22
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• 2012

Autosomal dominant polycystic kidney disease (ADPKD) is characterized by formation of multiple fluid-filled cysts that expand over time and destroy renal architecture. The proteins encoded by the $PKD1$ and $PKD2$ genes, mutations in which account for nearly all cases of ADPKD, may help guard against cystogenesis. Previously developed mouse models of $PKD1$ and $PKD2$ demonstrated an embryonic lethal phenotype and massive cyst formation in the kidney, indicating that $PKD1$ and $PKD2$ probably play important roles during normal renal tubular development. However, their precise role in development and the cellular mechanisms of cyst formation induced by $PKD1$ and $PKD2$ mutations are not fully understood. To address this question, we presently created $Pkd2$ knockout and $PKD2$ transgenic mouse embryo fibroblasts. We used a mouse oligonucleotide microarray to identify messenger RNAs whose expression was altered by the overexpression of the $PKD2$ or knockout of the $Pkd2$. The majority of identified mutations was involved in critical biological processes, such as metabolism, transcription, cell adhesion, cell cycle, and signal transduction. Herein, we confirmed differential expressions of several genes including aquaporin-1, according to different $PKD2$ expression levels in ADPKD mouse models, through microarray analysis. These data may be helpful in $PKD2$-related mechanisms of ADPKD pathogenesis.

• Proceedings of the Korean Society of Veterinary Clinics Conference
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• 2009.04a
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• pp.302-302
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• 2009

• Animal cells and systems
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• v.10 no.2
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• pp.65-71
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• 2006

Autosomal Dominant Polycystic Kidney Disease (ADPKD) is one of the most common inherited renal disorders in the world. Mutations in PKD1 located on chromosome 16p13.3 are responsible for 85% of all the ADPKD patients whereas mutations in PKD2 on chromosome 4q21-23 are responsible for the rest of the cases. Genetic heterogeneity and the problems of mutation detection in PKD1 suggest that linkage analysis is an important approach to study the genetics of ADPKD. To evaluate the availability of six (CA)n microsatellite markers for the linkage analysis of ADPKD in the Korean population, we examined the allele frequencies and heterozygosities of the markers. With the exception of KG8, five markers were highly informative, with PIC values over 0.5, but the PIC value of KG8 marker was less informative than other five markers because of the low number of alleles. Therefore, this study will be useful in linkage analysis for ADPKD families in the Korean population.