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1.  Transperitoneal Laparoscopic Nephrectomy for Autosomal Dominant Polycystic Kidney Disease 
Compared to open surgery, laparoscopic nephrectomy for autosomal dominant polycystic kidney disease appears to be a feasible and safe approach.
Objective:
This study focuses on laparoscopic nephrectomy for autosomal dominant polycystic kidney disease (ADPKD).
Material and Methods:
We retrospectively reviewed 21 consecutive patients who had previously undergone laparoscopy between 2007 and 2010. Data were compared to that obtained from 19 consecutive patients who had open surgery between 2004 and 2007. Clinical parameters, operative data, perioperative mortality, postoperative complications, and length of hospital stay were compared using χ2 and Student t tests for qualitative and quantitative variables, respectively.
Results:
Nephrectomy is usually performed to create space for renal transplantation (81% and 79%, respectively). Operating time was longer with the laparoscopic approach (180 min vs. 128 min, P = .001). Blood loss was comparable in the 2 groups (154 vs. 222 ml, P = .359) but 3 patients were transfused in the open surgery group as compared with 1 patient in the laparoscopic group. No conversion was needed. There was a trend in the laparoscopic group with respect to lower consumption of analgesics in the postoperative period (P = .06). Delay to transit recovery (2.1 d vs 4.1 d, P < .001) and hospital stay (5.2 d vs. 8.28 d, P = .002) were significantly decreased in the laparoscopic group. The interval from surgery to renal transplantation was lower in patients operated on laparoscopically (3.1 vs. 12 mo). Complications occurred in 33% of the patients in the laparoscopic group as compared with 68% in the open surgery group (P = .22). Severe complications were less frequent in the laparoscopic group (9.5% vs. 37%, P = .04).
Conclusion:
Laparoscopic nephrectomy is a feasible and safe procedure for ADPKD. Morbidity is significantly reduced compared with the open approach.
doi:10.4293/108680812X13462882736178
PMCID: PMC3535813  PMID: 23318070
Kidney; Renal insufficiency; Polycystic kidney; Laparoscopy
2.  Incidental renal cell carcinoma presenting in a renal transplant recipient with autosomal dominant polycystic kidney disease: a case report 
Introduction
We report an instructive case of incidental renal cell carcinoma in a patient with autosomal dominant polycystic kidney disease who underwent simultaneous bilateral native nephrectomy and living donor renal transplantation.
Case presentation
A 57-year-old Asian man with end-stage kidney disease due to autosomal dominant polycystic kidney disease received a living kidney graft from his brother. Because of recurrent infection, chronic pain and enlarged kidneys, he underwent a bilateral nephrectomy with concomitant renal transplantation. The total weight of the removed kidneys was 6kg; the maximal diameter of the larger kidney was 28cm. His left kidney had a 1cm diameter tumor. Pathology indicated papillary renal cell carcinoma. At the time of this report, the transplant kidney function was normal with no evidence of local recurrence or distant metastasis.
Conclusion
This case shows and reinforces the importance of considering the possibility of an occult malignancy in the native kidneys of patients with autosomal dominant polycystic kidney disease. Simultaneous bilateral native nephrectomy should be considered in these renal transplant recipients not only for preventing the development of adverse symptoms but also for detecting an occult malignancy.
doi:10.1186/1752-1947-6-154
PMCID: PMC3423017  PMID: 22691223
3.  Hand-Assisted Laparoscopic Nephrectomy for Polycystic Kidney Disease 
Hand-assisted laparoscopic nephrectomy for polycystic kidney disease seemed to result in shorter length of hospital stay and reduced need for transfusion compared with patients undergoing the same procedure with an open technique.
Background and Objectives:
Historically, nephrectomy for autosomal dominant polycystic kidney disease was performed by an open technique. We performed this study to compare outcomes in hand-assisted laparoscopic nephrectomy with open nephrectomy in this population.
Methods:
Charts of patients with autosomal dominant polycystic kidney disease who underwent nephrectomy by a transplant surgeon from January 1, 2000, to December 31, 2011, were reviewed. The hand-assisted laparoscopic nephrectomy group was compared with the open group. Data collected included unilateral versus bilateral nephrectomy, operative time, complications, transfusion requirement, and length of stay.
Results:
Of the 78 patients identified, 18 underwent open transabdominal nephrectomy, 56 underwent hand-assisted laparoscopic nephrectomy, and 2 underwent hand-assisted laparoscopic nephrectomy that was converted to an open procedure. Two patients were excluded because another major procedure was performed at the same time as the nephrectomy. Operative times were similar. Patients undergoing open bilateral nephrectomy were more likely to receive transfusion (odds ratio, 3.57 [95% confidence interval, 0.74–17.19]; P = .016), and the length of stay was longer in the open groups (5.9 days vs 4.0 days for unilateral [P = .013] and 7.8 days vs 4.6 days for bilateral [P = .001]). Overall complication rates were similar. The most frequent complications associated with hand-assisted laparoscopic nephrectomy were the development of an incisional hernia at the hand-port site and arteriovenous fistula thrombosis.
Conclusion:
Hand-assisted laparoscopic nephrectomy can be safely performed without increased operative times or complications. The hand-assisted laparoscopic nephrectomy group enjoyed a shorter length of stay, and fewer patients in this group received transfusion. For patients considering renal transplantation, avoidance of transfusion is important to prevent sensitization and limiting access to compatible organs.
doi:10.4293/108680813X13654754535719
PMCID: PMC3771795  PMID: 23925022
Nephrectomy; Polycystic kidney disease
4.  Autosomal dominant polycystic kidney disease with ectopic unilateral multicystic dysplastic kidney 
BMC Nephrology  2013;14:38.
Background
Autosomal dominant polycystic kidney disease (ADPKD) is the most common hereditary renal disorder. In most cases, ADPKD similarly affects bilateral kidneys.
Case presentation
Among the 605 ADPKD patients that were followed up by our center, we identified two male patients with unilateral ADPKD. The cases were remarkable because the patients also had ectopia and multicystic dysplasia in the contralateral kidney, which are generally sporadic disease conditions. Both patients tested positive for polycystic kidney disease 1 mutation, but negative for hepatocyte nuclear factor 1 beta mutation. Moreover, the deterioration of their kidney function seemed to be quicker than their age- and sex-matched controls and siblings. Both patients had started a long-term hemodialysis in their 40s.
Conclusion
Anatomical and genetic abnormality in patients with ADPKD may be more frequent and complex than previously believed. The compensatory capacity in patients with ADPKD is fragile, and missing one kidney could accelerate the deterioration of renal function.
doi:10.1186/1471-2369-14-38
PMCID: PMC3601018  PMID: 23413949
Autosomal dominant polycystic kidney disease; Ectopia; Multicystic dysplasia; Unilateral
5.  Acute Kidney Injury in ADPKD Patients with Pneumonia 
Background. In animal models, polycystic kidneys are susceptible to acute kidney injury (AKI). We examined the occurrence of AKI in a cohort of autosomal dominant polycystic kidney disease (ADPKD) and non-ADPKD patients with acute pneumonia. Design. All ADPKD patients admitted to Mayo Clinic Rochester for pneumonia from January 1990 to April 2010 were examined. Sixty-three patients had lobar infiltration and consolidation on chest X-ray. After excluding patients on dialysis, with organ transplantation, and on chronic immunosuppression, 24 remaining ADPKD patients were enrolled. Twenty-three of the 24 were matched with 92 (1 : 4 ratio) non-ADPKD pneumonia patients based on their baseline eGFR. AKI was defined as serum creatinine elevation ≥0.3 mg/dL. Results. Sixteen of the 23 ADPKD patients (69.6%) and 36 of the 92 (39.1%) non-ADPKD patients developed AKI, P = 0.008. In both groups, those who developed AKI had a lower baseline eGFR (41.1 ± 5.00 versus 58.7 ± 11.8 in ADPKD and 40.2 ± 3.65 versus 51.8 ± 2.24 mL/min/1.73 m2 in the non-ADPKD group), more intensive care unit admissions, and longer hospital stays. AKI was associated with a reduced survival in both groups. Conclusions. Patients with ADPKD admitted for acute pneumonia had more frequent episodes of AKI than non-ADPKD patients with comparable kidney function.
doi:10.4061/2011/617904
PMCID: PMC3144716  PMID: 21811681
6.  Unilateral autosomal dominant polycystic kidney disease with contralateral renal agenesis: a case report. 
Journal of Korean Medical Science  2003;18(2):284-286.
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.
PMCID: PMC3055028  PMID: 12692431
7.  Molecular genetic diagnosis of autosomal dominant polycystic kidney disease in a newborn with bilateral cystic kidneys detected prenatally and multiple skeletal malformations. 
Journal of Medical Genetics  1993;30(5):419-422.
We report a case of an unusual prenatal presentation of polycystic kidneys associated with multiple skeletal limb defects, including polydactyly, syndactyly, bilateral agenesis of the tibia, and club foot. The ultrasonographic picture was consistent with a diagnosis of polycystic kidney disease, either the adult onset autosomal dominant type (ADPKD) or the early onset autosomal recessive form (ARPKD). However, there was a positive family history for ADPKD. Linkage analysis was performed in 10 family members, of whom four were affected, using six flanking DNA markers tightly linked to the PKD1 locus on chromosome 16p, and one marker linked to the putative PKD2 locus on chromosome 2p. Lod score determinations indicated that the affected gene in the family is most likely PKD1. The patient inherited the disease linked haplotype from his affected mother.
Images
PMCID: PMC1016382  PMID: 8320707
8.  The impact of type II diabetes mellitus in patients with autosomal dominant polycystic kidney disease 
Nephrology Dialysis Transplantation  2011;27(7):2862-2865.
Background
The epidemic of obesity and diabetes is increasing within the USA and worldwide. We have previously shown that body mass index has increased significantly in autosomal dominant polycystic kidney disease (ADPKD) subjects seen at our center in more recent years. However, the impact of Type II diabetes in ADPKD patients has not been well studied.
Methods
This retrospective cohort study compared clinical characteristics in 44 pre-renal transplant patients with ADPKD and diabetes and 88 age- and sex-matched non-diabetic patients with ADPKD who were seen at the University of Colorado between 1977 and 2008. The primary outcomes in this study were renal volume determined by renal ultrasonography, renal function assessed by estimated glomerular filtration rate and time to onset of end-stage renal disease or death by Kaplan–Meier analyses.
Results
Diabetic patients had significantly larger kidney volumes than those with ADPKD alone [geometric mean (95% confidence interval (CI)]: 2456 (1510–3992) versus 1358 (1186–1556) cm3, P = 0.02. Among those whose age at hypertension diagnosis was known, the diabetic ADPKD patients had earlier median (95% CI) age at onset of hypertension compared to those with ADPKD alone: 32.5 (28–40) versus 38 (35–42) years, P = 0.04. Diabetic ADPKD patients tended to have an earlier median age of death than those with ADPKD alone.
Conclusions
Patients with ADPKD and type II diabetes have larger renal volumes, earlier age at diagnosis of hypertension and may die at a younger age compared to those patients with ADPKD alone. This study emphasizes the importance of diabetes risk management in ADPKD.
doi:10.1093/ndt/gfr744
PMCID: PMC3398061  PMID: 22207329
ADPKD; chronic kidney disease; diabetes; hypertension; renal failure
9.  Atypical Presentation of Perforated Sigmoid Diverticulitis in a Kidney Transplant Recipient with Autosomal Dominant Polycystic Kidney Disease 
Perforated sigmoid diverticulitis, a complication of colonic diverticulosis commonly associated with autosomal dominant polycystic kidney disease (ADPKD), can be life-threatening in allogeneic kidney transplant recipients in the postoperative period. Immunosuppressive medications not only place the patient at risk for intestinal perforation, but also mask classic clinical symptoms and signs of acute abdomen, and subsequently lead to delayed diagnosis and treatment. We report a case of an ADPKD patient post kidney transplantation presenting with nausea, vomiting, and abdominal pain without signs of peritonitis. Chest x-ray revealed free air under the diaphragm consistent with intestinal perforation. Post kidney transplant recipients with ADPKD presenting with abdominal pain should prompt a search for possible perforated colonic diverticulitis in order to diagnose and treat this life-threatening condition early.
PMCID: PMC3727570  PMID: 23901392
autosomal dominant polycystic kidney disease (ADPKD); diverticulitis; diverticulosis; kidney transplant
10.  Positron emission tomography in the diagnostic pathway for intracystic infection in adpkd and "cystic" kidneys. a case series 
BMC Nephrology  2011;12:48.
Background
Intracystic infection, in Autosomal Dominant Polycystic Kidney Disease (ADPKD) and in kidneys with multiple cysts, is a diagnostic and therapeutic challenge, as conventional imaging techniques may not discriminate among "complicated" cysts (infection, bleeding, neoplasia), and as the clinical picture may be attenuated, in particular in early phases. Positron Emission Tomography with fluorodeoxyglucose (FDG-PET) was recently suggested as a tool to detect infection in ADPKD, in single cases and small series.
The aim of the study was to report on the role of FDG-PET in the work-up of 10 cases of suspected cystic infections, affected by ADPKD or with multiple kidney cysts.
Methods
Observational study. Review of clinical charts and of the imaging data since the use of FDG-PET for detecting cystic infections (2008-2010).
Results
In 2008-2010, 6 patients with ADPKD and 4 with multiple kidney cysts were referred for suspected intracystic infections (3 males, 7 females, aged 55-83 years, in all CKD stages); in one case the imaging was done in the work-up of a complicated "uremic" cyst. The clinical picture, the usual inflammatory markers and/or the conventional imaging techniques did not allow conclusive diagnosis at referral or during follow-up (ultrasounds in all, CT in 8/10). Nine patients displayed inflammatory signs (increase in C-reactive protein and other biochemical markers) and constitutional symptoms (fever in 9/10).
FDG-PET was positive in 6 cases (5 kidney and 1 liver cyst), was repeated during follow-up in 4 patients and was negative in 4 cases. In the positive cases, FDG-PET guided the therapeutic choices; in particular, the duration of therapy was supported by imaging data in the 4 cases with multiple scans. No relapse was recorded after discontinuation of antibiotic therapy in the treated patients. The negative cases did not develop clinical signs of cystic infection over follow-up.
Conclusion
In this case series, the largest prospective one so far published and the only one including different types of renal cysts, FDG-PET is confirmed as a promising diagnostic tool for detecting intracystic infection in ADPKD and in multiple kidney cysts, and a potential guide for tailoring therapy. Further larger and multicenter studies are needed to evaluate the cost-benefit ratio and the limits of this imaging technique in the clinical setting.
doi:10.1186/1471-2369-12-48
PMCID: PMC3197475  PMID: 21957932
Positron emission tomography; polycystic kidney disease; infection; kidney cysts; long-term antibiotic therapy
11.  Post transplant urinary tract infection in Autosomal dominant polycystic kidney disease a perpetual diagnostic dilema - 18-fluorodeoxyglucose - Positron emission computerized tomography - A valuable tool 
Urinary tract infection (UTI) is the most common infection contracted by renal allograft recipients. In patients of autosomal dominant polycystic kidney disease (ADPKD), cyst infection presents a complex diagnostic and therapeutic challenge especially in the post transplant period. Accurate diagnosis forms the cornerstone in salvaging the graft from potentially catastrophic outcome. We describe a case of xanthogranulomatous pyelonephritis (XPN) in the native kidney in a patient of post transplant ADPKD which presented as frequently relapsing UTI with graft dysfunction where in accurate diagnosis was made possible with the aid of 18-fluorodeoxyglucose (FDG) - Positron emission computerized tomography (PET/CT).
doi:10.4103/0972-3919.90266
PMCID: PMC3237213  PMID: 22174521
ADPKD; PET/CT; transplantation; UTI; xanthogranulomatous pyelonephritis
12.  Bilateral hand-assisted laparoscopic nephrectomy in adult polycystic kidney disease patients: a UK centre experience 
Journal of Medicine and Life  2012;5(2):226-231.
Purpose: We report our experience with bilateral hand-assisted laparoscopic nephrectomy in patients with adult polycystic kidney disease.
Materials & methods: Between November 2009 and November 2010, 3 patients with adult polycystic kidney disease underwent bilateral hand-assisted laparoscopic nephrectomy in our institution. Indications for bilateral nephrectomy included recurrent cyst hemorrhage, impaired gastrointestinal function and early satiety due to direct intestinal compression by large polycystic kidneys, and anatomical lack of space for future renal transplantation. We retrospectively reviewed the records of these patients and we are reporting our experience.
Results: All three patients successfully underwent bilateral hand-assisted laparoscopic nephrectomy with a mean operating time of 208 minutes (range 195 to 220). There were no conversions to open procedure. Blood loss was less than 100 ml in all cases. Mean renal unit size was of 2037 g (range 1798 to 2214). Hospital stay ranged from 10 to 12 days. One patient developed a chest infection postoperatively and suffered from a prolonged ileus. Another patient developed a retroperitoneal hematoma, which was treated conservatively.
Conclusions: Bilateral hand-assisted laparoscopic nephrectomy is a feasible and safe procedure in adult polycystic kidney disease patients, which has potential benefits of a shorter hospital stay and reduced morbidity and mortality in comparison to open procedure.
PMCID: PMC3391893  PMID: 22802898
laparoscopy; nephrectomy; laparoscopic nephrectomy; hand-assisted laparoscopic nephrectomy; adult polycystic kidney disease
13.  Risk of intracranial hemorrhage associated with autosomal dominant polycystic kidney disease in patients with end stage renal disease 
BMC Nephrology  2014;15:39.
Background
An analysis of intracranial hemorrhage (ICH) in a national sample of autosomal dominant polycystic kidney disease (ADPKD) patients receiving long-term dialysis has not been reported. It is often assumed that patients with ADPKD are not at increased risk of ICH after starting dialysis. We hypothesized that patients with ADPKD would have a higher subsequent risk of ICH even after the start of chronic dialysis.
Methods
Retrospective cohort study of Medicare primary patients with and without ADPKD in the United States Renal Data System (USRDS), initiated on chronic dialysis or transplanted between 1 January 1999 and 3 July 2009, and followed until 31 December 2009. Covariates included age, gender, race, prior stroke, diabetes mellitus, dialysis modality, body mass index, serum albumin and other co-morbid conditions from the Medical Evidence Form. Primary outcome was ICH, based on inpatient and outpatient Medicare claims, and all-cause mortality. Kaplan-Meier analysis was used for unadjusted assessment of time to events. Cox regression was used for assessment of factors associated with ICH and mortality. We performed competing risk regression using kidney transplant and death as competing risks. Kidney transplant was also modeled as a time-dependent covariate in Cox regression.
Results
Competing risk regression demonstrated that ADPKD had a subhazard ratio 2.97 for ICH (95% CI 2.27-3.89). Adjusted Cox analysis showed that ADPKD patients had an AHR for death of 0.59 vs. non-ADPKD patients (95% CI 0.57-0.61).
Conclusions
ADPKD is a significant risk factor for ICH among patients on maintenance dialysis. Our Medicare primary cohort was older than in previous studies of intracranial aneurysm rupture among ADPKD patients. There are also limitations inherent to using the USRDS database.
doi:10.1186/1471-2369-15-39
PMCID: PMC3939494  PMID: 24571546
Intracranial hemorrhage; Intracranial aneurysm; Autosomal dominant polycystic kidney disease; Stroke; Dialysis; USRDS; Competing risk
14.  Emphysematous polycystic renal infection 
Indian Journal of Nephrology  2010;20(4):205-206.
Autosomal dominant polycystic kidney disease (ADPKD) is one of the commonest hereditary disorders. Urinary tract infection is a common complication of this disease. However emphysematous infections in ADPKD have seldom been reported. We report a case of emphysematous polycystic renal infection with Gram negative (Escherichia coli) septicemia in a nondiabetic patient with ADPKD who succumbed to his illness despite aggressive management including early nephrectomy.
doi:10.4103/0971-4065.73457
PMCID: PMC3008950  PMID: 21206683
Autosomal dominant polycystic kidney disease; emphysematous polycystic renal infection; pyopneumocyst
15.  Compromised Cytoarchitecture and Polarized Trafficking in Autosomal Dominant Polycystic Kidney Disease Cells 
The Journal of Cell Biology  2000;149(1):111-124.
Cystogenesis associated with autosomal dominant polycystic kidney disease (ADPKD) is characterized by perturbations in the polarized phenotype and function of cyst-lining epithelial cells. The polycystins, the protein products of the genes mutated in the majority of ADPKD cases, have been described recently, but the pathological mechanism by which causal mutations result in the mislocalization of cell membrane proteins has remained unclear. This report documents the dissociation from the ADPKD cell basolateral membrane of three molecules essential for spatial organization and exocytosis. The adherens junction protein E-cadherin, the subcellular disposition of which governs intercellular and intracellular architecture, was discovered sequestered in an internal ADPKD cell compartment. At the same time, sec6 and sec8, components of a complex critical for basolateral cargo delivery normally arrayed at the apico-lateral apex, were depleted from the ADPKD cell plasma membrane. An analysis of membrane transport revealed that basolateral trafficking of proteins and lipids was impaired as a result of delayed cargo exit from the ADPKD cell Golgi apparatus. Apical transport proceeded normally. Taken together with recent documentation of an association between polycystin-1 and E-cadherin (Huan and van Adelsberg 1999), the data suggest that causal mutations disrupt E-cadherin–dependent cytoarchitecture, adversely affecting protein assemblies crucial for basolateral trafficking.
PMCID: PMC2175108  PMID: 10747091
basolateral; adherens junction; epithelia; autosomal dominant polycystic kidney disease (ADPKD); polycystin
16.  Nephrectomy in patients with Caroli’s and ADPKD may be associated with increased morbidity 
Autosomal dominant polycystic kidney disease (ADPKD), characterized by multiple bilateral renal cysts, is the most common inherited disorder of the kidney and an important cause of end-stage renal disease (ESRD). Caroli’s disease is a much less frequent condition with ectasia of the intrahepatic biliary system. A clear association between autosomal recessive and Caroli’s disease has been described, but only 4 cases of ADPKD and Caroli’s disease have been reported with 2 postoperative mortalities. The aim of this case is to increase the awareness of intra-operative and postoperative complications. A 66 year-old male was diagnosed with ADPKD and Caroli’s disease with hepatosplenomegaly and 4 episodes of ascending cholangitis. After 3 years of hemodialysis for ESRD, he received a cadaveric renal allograft. Subsequently, he developed paroxysmal atrial fibrillation. Upon anticoagulation, he developed multiple episodes of gross hematuria from the left native kidney. After the anticoagulation therapy was discontinued, he underwent bilateral nephrectomies of his native kidneys. Intra-operatively, a splenic laceration could not be managed conservatively. Therefore, splenectomy was performed. In addition, he developed ascending cholangitis post-operatively that was treated with antibiotics. He was discharged on postoperative day 18. Genetic testing revealed that the patient is heterozygote for a large deletion in PKD1 gene, which encompasses all tested exons (exons 1–44).
doi:10.5489/cuaj.10054
PMCID: PMC3104419  PMID: 21470545
17.  Acute abdomen and ascites as presenting features of autosomal dominant polycystic kidney disease 
World Journal of Hepatology  2012;4(12):394-398.
We describe a patient with sudden onset of abdominal pain and ascites, leading to the diagnosis of autosomal dominant polycystic kidney disease (ADPKD). Her presentation was consistent with acute liver cyst rupture as the cause of her acute illness. A review of literature on polycystic liver disease in patients with ADPKD and current management strategies are presented. This case alerts physicians that ADPKD could occasionally present as an acute abdomen; cyst rupture related to ADPKD may be considered in the differential diagnoses of acute abdomen.
doi:10.4254/wjh.v4.i12.394
PMCID: PMC3554804  PMID: 23355918
Autosomal dominant polycystic kidney disease; Acute abdominal pain; Ascites; Polycystic liver disease
18.  Therapeutic mTOR Inhibition in Autosomal Dominant Polycystic Kidney Disease: What Is the Appropriate Serum Level? 
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
doi:10.1111/j.1600-6143.2010.03152.x
PMCID: PMC3697013  PMID: 20642692
Disease transmission; DNA sequencing; donor risk; mTOR inhibitor; peripheral blood; polycystic kidney disease; renal allograft biopsies; renal medicine; sirolimus
19.  TGF-β Mediated Epithelial-Mesenchymal Transition in Autosomal Dominant Polycystic Kidney Disease 
Yonsei Medical Journal  2009;50(1):105-111.
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 α-SMA, E-cadherin, vimentin, TGF-β1 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 α-SMA+ myofibroblasts in ADPKD. Cystic tubular epithelial cells in ADPKD lost epithelial marker (E-cadherin) and expressed mesenchymal markers (α-SMA, vimentin). There were significant increases of α-SMA (34.3 ± 11.7% vs 0.9 ± 1.5%), vimentin (19.9 ± 3.9% vs 3.3 ± 1.4%), TGF-β1 (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-β, Smad 2/3 and markers of EMT. It suggests that TGF-β mediated EMT has a role in progression of ADPKD.
doi:10.3349/ymj.2009.50.1.105
PMCID: PMC2649848  PMID: 19259356
Epithelial mesenchymal transition; antosomal dominant polycystic kidney disease
20.  Marginal donor kidney in a marginal recipient: Five year follow-up 
Indian Journal of Nephrology  2010;20(2):100-102.
The widening gap between demand and supply of organs became apparent as organ shortage became more severe. Organs previously considered unsuitable for transplantation are currently being used. Autosomal dominant polycystic kidney disease (ADPKD) is a hereditary disease characterized by slow progressive cystic changes and deterioration of renal function. We provide our experience with an ADPKD patient who received a kidney from 38-year-old deceased donor ADPKD-affected kidney for renal transplantation.
doi:10.4103/0971-4065.65306
PMCID: PMC2931124  PMID: 20835327
Autosomal dominat polycystic kidney disease; cadaveric donor; marginal donor
21.  Chronic asymptomatic pyuria precedes overt urinary tract infection and deterioration of renal function in autosomal dominant polycystic kidney disease 
BMC Nephrology  2013;14:1.
Background
Urinary tract infection (UTI) occurs in 30%-50% of individuals with autosomal dominant polycystic kidney disease (ADPKD). However, the clinical relevance of asymptomatic pyuria in ADPKD patients remains unknown.
Methods
We retrospectively reviewed medical records of 256 ADPKD patients who registered to the ADPKD clinic at Seoul National University Hospital from Aug 1999 to Aug 2010. We defined the asymptomatic pyuria as more than 5-9 white blood cells in high-power field with no related symptoms or signs of overt UTI. Patients were categorized into 2 groups depending on its duration and frequency: Group A included non-pyuria and transient pyuria patients; Group B included recurrent and persistent pyuria patients. The association between asymptomatic pyuria and both the development of overt UTI and the deterioration of renal function were examined.
Results
With a mean follow-up duration of 65.3 months, 176 (68.8%) out of 256 patients experienced 681 episodes of asymptomatic pyuria and 50 episodes of UTI. The annual incidence of asymptomatic pyuria was 0.492 episodes/patient/year. The patients in group B showed female predominance (58.5% vs. 42.0%, P=0.01) and experienced an upper UTI more frequently (hazard ratio: 4.612, 95% confidence interval: 1.735-12.258; P=0.002, adjusted for gender and hypertension). The annual change in estimated glomerular filtration rate (ΔeGFR) was significantly larger in magnitude in group B than in group A (-2.7±4.56 vs. -1.17±5.8, respectively; P=0.01). Age and Group B found to be the independent variables for ΔeGFR and developing end-stage renal disease (16.0% vs. 4.3%, respectively; P=0.001).
Conclusions
Chronic asymptomatic pyuria may increase the risk of developing overt UTI and may contribute to declining renal function in ADPKD.
doi:10.1186/1471-2369-14-1
PMCID: PMC3545884  PMID: 23295127
Polycystic kidney disease; Chronic renal failure; Glomerular filtration rate; Pyuria; Urinary tract infection
22.  Quality of life of patients with ADPKD—Toranomon PKD QOL study: cross-sectional study 
BMC Nephrology  2013;14:179.
Background
The quality of life (QOL) of patients with autosomal dominant polycystic kidney disease (ADPKD) has not been investigated well. This study was performed to clarify the QOL of patients with ADPKD and to identify factors that affected their QOL.
Methods
The present cross-sectional study is part of a prospective observational study on the QOL of ADPKD patients. Patients with ADPKD who were referred to Toranomon Hospital between March 2010 and November 2012 were enrolled. The short form-36 (SF-36) questionnaire and our original 12-item questionnaire were used to evaluate QOL. We analyzed the results of the questionnaire survey and then investigated correlations between QOL and clinical features.
Results
A total of 219 patients (93 men and 126 women) were enrolled and their mean age was 55.1±10.8 years. There were 108 patients on dialysis. The SF-36 scores (PCS, MCS, and RCS) of all patients were significantly lower than the mean scores for the Japanese population. Stepwise multiple regression analysis demonstrated that Hb, serum Alb, ascites, and cerebrovascular disease all had a significant influence on the PCS, while mental disease had a significant influence on the MCS and serum Alb significantly influenced the RCS. The total liver and kidney volume (TLKV) and the dialysis status were not significantly associated with any of the SF-36 scores by multiple regression analysis, but TLKV was closely correlated with abdominal distention and distention had an important influence on QOL. Pain, sleep disturbance, heartburn, fever, gross hematuria, and anorexia also affected QOL, but these variables were not correlated with TLKV.
Conclusions
Several factors influence QOL, so improving symptoms unrelated to TLKV as well as reducing abdominal distention can improve the QOL of ADPKD patients.
doi:10.1186/1471-2369-14-179
PMCID: PMC3765978  PMID: 23978051
Quality of life; Polycystic kidney disease; Dialysis; Total liver and kidney volume
23.  Urine MicroRNA as Potential Biomarkers of Autosomal Dominant Polycystic Kidney Disease Progression: Description of miRNA Profiles at Baseline 
PLoS ONE  2014;9(1):e86856.
Background
Autosomal dominant polycystic kidney disease (ADPKD) is clinically heterogenic. Biomarkers are needed to predict prognosis and guide management. We aimed to profile microRNA (miRNA) in ADPKD to gain molecular insight and evaluate biomarker potential.
Methods
Small-RNA libraries were generated from urine specimens of ADPKD patients (N = 20) and patients with chronic kidney disease of other etiologies (CKD, N = 20). In this report, we describe the miRNA profiles and baseline characteristics. For reference, we also examined the miRNA transcriptome in primary cultures of ADPKD cyst epithelia (N = 10), normal adult tubule (N = 8) and fetal tubule (N = 7) epithelia.
Results
In primary cultures of ADPKD kidney cells, miRNA cistrons mir-143(2) (9.2-fold), let-7i(1) (2.3-fold) and mir-3619(1) (12.1-fold) were significantly elevated compared to normal tubule epithelia, whereas mir-1(4) members (19.7-fold), mir-133b(2) (21.1-fold) and mir-205(1) (3.0-fold) were downregulated (P<0.01). Expression of the dysregulated miRNA in fetal tubule epithelia resembled ADPKD better than normal adult cells, except let-7i, which was lower in fetal cells. In patient biofluid specimens, mir-143(2) members were 2.9-fold higher in urine cells from ADPKD compared to other CKD patients, while expression levels of mir-133b(2) (4.9-fold) and mir-1(4) (4.4-fold) were lower in ADPKD. We also noted increased abundance mir-223(1) (5.6-fold), mir-199a(3) (1.4-fold) and mir-199b(1) (1.8-fold) (P<0.01) in ADPKD urine cells. In ADPKD urine microvesicles, miR-1(2) (7.2-fold) and miR-133a(2) (11.8-fold) were less abundant compared to other CKD patients (P<0.01).
Conclusions
We found that in ADPKD urine specimens, miRNA previously implicated as kidney tumor suppressors (miR-1 and miR-133), as well as miRNA of presumed inflammatory and fibroblast cell origin (miR-223/miR-199), are dysregulated when compared to other CKD patients. Concordant with findings in the primary tubule epithelial cell model, this suggests roles for dysregulated miRNA in ADPKD pathogenesis and potential use as biomarkers. We intend to assess prognostic potential of miRNA in a followup analysis.
doi:10.1371/journal.pone.0086856
PMCID: PMC3906110  PMID: 24489795
24.  Characteristics of Intracranial Aneurysms in the Else Kröner-Fresenius Registry of Autosomal Dominant Polycystic Kidney Disease 
Background
Patients who harbor intracranial aneurysms (IAs) run a risk for aneurysm rupture and subsequent subarachnoid hemorrhage which frequently results in permanent deficits or death. Prophylactic treatment of unruptured aneurysms is possible and recommended depending on the size and location of the aneurysm as well as patient age and condition. IAs are major manifestations of autosomal dominant polycystic kidney disease (ADPKD). Current guidelines do not suggest surveillance of IAs in ADPKD except in the setting of family history if IA was known in any relative with ADPKD. Management of IAs in ADPKD is problematic because limited data exist from large studies.
Methods
We established the Else Kröner-Fresenius Registry for ADPKD in Germany. Clinical data were assessed for age at diagnosis of IAs, stage of renal insufficiency, and number, location and size of IAs as well as family history of cerebral events. Patients with symptomatic or asymptomatic IAs were included. All patients with ADPKD-related IAs were offered mutation scanning of the susceptibility genes for ADPKD, the PKD1 and PKD2 genes.
Results
Of 463 eligible ADPKD patients from the population base of Germany, 32 (7%) were found to have IAs, diagnosed at the age of 2–71 years, 19 females and 13 males. Twenty (63%) of these 32 patients were symptomatic, whereas IAs were detected in an asymptomatic stage in 12 patients. IAs were multifocal in 12 and unifocal in 20 patients. In 26 patients (81%), IAs were diagnosed before end-stage renal failure. Twenty-five out of 27 unrelated index cases (93%) had no IAs or cerebral events documented in their relatives with ADPKD. In 16 unrelated index patients and 3 relatives, we detected germline mutations. The mutations were randomly distributed across the PKD1 gene in 14 and the PKD2 gene in 2 index cases. Questionnaires answered for 320/441 ADPKD patients without IAs revealed that only 45/320 (14%) had MR angiography.
Conclusion
In ADPKD, rupture of IAs occurs frequently before the start of dialysis, is only infrequently associated with a family history of IAs or subarachnoid hemorrhage, and is associated with mutations either of the PKD1 or the PKD2 gene of any type. Screening for IAs is widely insufficiently performed, should not be restricted to families with a history of cerebral events and should be started before end-stage renal failure.
doi:10.1159/000342620
PMCID: PMC3492998  PMID: 23139683
Intracranial aneurysms; Autosomal dominant polycystic kidney disease; Preventive medicine
25.  Absence of mTOR Inhibitor Effect on Hepatic Cyst Growth: A Case Report of a Kidney Transplant Recipient with Autosomal Dominant Polycystic Kidney Disease 
Some experimental studies have suggested a beneficial effect of the mammalian target of rapamycin (mTOR) inhibitor use on hepatic and renal cyst growth in patients with autosomal dominant polycystic kidney disease (ADPKD). However, the results of clinical studies are conflicting and the role of mTOR inhibitors is still uncertain. We report the case of a patient with ADPKD who underwent deceased kidney transplantation because of an end-stage renal disease. The evolution was uneventful with an excellent graft function under cyclosporine (CsA) monotherapy. Some years later, the patient developed a symptomatic hepatomegaly due to growth of cysts. CsA was replaced by sirolimus, an mTOR inhibitor, in order to reduce or control the increase in the cyst and liver volume. Despite the switch, the hepatic volume increased by 25% in two years. Finally sirolimus was stopped because of the lack of effect on hepatic cyst growth and the presence of sirolimus side effects. The interest of our case resides in the followup by MRI imaging during the mTOR inhibitor treatment and 15 months after the restart of the initial immunosuppressive therapy. This observation indicates that mTOR inhibitors did not have significant effect on cyst-associated hepatic growth in our patient, which is consistent with some results of recent large clinical studies.
doi:10.1155/2012/513025
PMCID: PMC3530859  PMID: 23304619

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