Incidental renal cell carcinoma post bilateral nephrectomy in autosomal dominant polycystic kidney disease

BACKGROUND Renal cell carcinoma(RCC)is more common in patients with autosomal dominant polycystic kidney disease(ADPKD)than in the general population.Diagnosing RCC in ADPKD is challenging due to the presence of multiple renal cysts,often leading to delays and difficulties in distinguishing RCC from cyst infection or hemorrhage.A total of 38 kidneys were excised from 19 patients,with a mean age of 56.8 years and an average hemodialysis duration of 84.2 months.Eight patients underwent open nephrectomies,and 11 underwent hand-assisted laparoscopic nephrec-tomies.RCC was detected in 15.8%of kidneys,affecting 21.1%of patients.Two patients had multifocal RCC in both kidneys.All RCC cases were pT1 stage,with the largest lesion averaging 16.5 mm in diameter.The average operative duration was 120 minutes,with intraoperative blood loss averaging 184.2 mL.Five patients required blood transfusions.Postoperative complications occurred in five patients,with a mean hospital stay of 17.1 days.The mean follow-up period was 28.1 months.CONCLUSION The prevalence of RCC is higher in patients with ADPKD with ESRD than in those with ESRD alone.Thus,clinicians should be cautious and implement surveillance programs to monitor the development of RCC in patients with ADPKD,particularly those on dialysis.

Safety and efficacy of transcatheter arterial embolization in autosomal dominant polycystic kidney patients with gross hematuria: Six case reports

BACKGROUND To retrospectively report the safety and efficacy of renal transcatheter arterial embolization for treating autosomal dominant polycystic kidney disease(ADPKD)patients with gross hematuria.CASE SUMMARY The purpose of this study is to retrospectively report the safety and efficacy of renal transcatheter arterial embolization for treating ADPKD patients with gross hematuria.Materials and methods:During the period from January 2018 to December 2019,renal transcatheter arterial embolization was carried out on 6 patients with polycystic kidneys and gross hematuria.Renal arteriography was performed first,and then we determined the location of the hemorrhage and performed embolization under digital subtraction angiography monitoring.Improvements in routine blood test results,routine urine test results,urine color and postoperative reactions were observed and analyzed.Results:Renal transcatheter arterial embolization was successfully conducted in 6 patients.The indices of 5 patients and the color of gross hematuria improved after surgery compared with before surgery.No severe complication reactions occurred.CONCLUSION For autosomal dominant polycystic kidney syndrome patients with gross hematuria,transcatheter arterial embolization was safe and effective.

Investigation of Demographic and Clinical Data of Patients with Autosomal Dominant Polycystic Kidney Disease

Background: Autosomal dominant polycystic kidney disease (ADPKD) is an important etiological factor causing chronic kidney disease (CKD), cardiovascular diseases and hypertension (HT). The purpose of the present study is to investigate the clinical information and demographic characteristics of autosomal dominant polycystic kidney disease patients who received treatment at our hospital for the last five years. Material and Method: Among 21400 people who sought care at Siirt State Hospital Urology and Nephrology Outpatient Clinics between January 2015 and January 2020 for various reasons, a total of 36 patients experiencing autosomal dominant polycystic kidney disease were included in the present research. Retrospective patient file access was used to gather demographic information and laboratory data. Results: The study included 36 patients in all, 25 (69.4%) male and 11 (30.6%) female. The patient’s average age was 50.8 ± 19.0. The average age at diagnosis was 43.4 ± 17.2. Family history was positive in 29 (80.5%) of the patients. There were hypertension in 27 (75.0%) patients, coronary artery disease in five (13.9%) patients, diabetes mellitus in five (13.9%) patients, left ventricular hypertrophy in 18 (50%) patients, proteinuria in 11 (30.6%) patients, and six (16.7%) patients had macroscopic hematuria. Liver cysts were found in 23 (63.9%) of the patients and nephrolithiasis in eight (22.2%). Discussion: Hypertension is the most common finding when clinical and demographic data of autosomal dominant polycystic kidney disease are examined. Providing blood pressure control reduces the risk of death due to left ventricular hypertrophy and slows down the rate at which chronic kidney disease progresses. The rate was found to be 80.5% for patients with a positive family history. It may be possible to diagnose and treat people with autosomal dominant polycystic kidney disease earlier by screening their family members.

Simultaneous kidney transplantation and ipsilateral native nephrectomy in patients with autosomal dominant polycystic kidney disease

The simultaneous kidney transplantation and ipsilateral native nephrectomy for autosomal dominant polycystic kidney disease does not seem to be associated with increased rates of comorbidity and complications.This outcome can efficiently be achieved when the indication and surgical approach of native nephrectomy are properly justified.

A Presumed Synonymous Mutation of PKD2 Caused Autosomal Dominant Polycystic Kidney Disease in a Chinese Family

Objective:Autosomal dominant polycystic kidney disease(ADPKD)is mainly caused by the pathogenic mutation of PKD1 or PKD2 gene and usually affects bilateral kidneys.Synonymous mutations are generally assumed to be neutral as they do not alter amino acids.Herein,we described an extremely rare ADPKD child caused by a heterozygous synonymous mutation of PKD2 gene accompanied by massive proteinuria and congenital solitary kidney.Methods:Clinical characteristics of the patients were summarized.Whole-exome sequencing was performed to screen the disease-causing gene mutation,and reverse transcription polymerase chain reaction(RT-PCR)and Sanger sequencing were applied to analyze the impact of the identified mutation on gene transcription and splicing.Results:Polycystic changes were found in the solitary kidney of a girl initially presented with nephrotic-range proteinuria.Thereafter her mother and 2 other family members were diagnosed to be ADPKD.Whole-exome sequencing of the proband identified a heterozygous synonymous mutation(c.1716G>A,p.Lys572=)located in the splicing site of exon 7 in PKD2 gene,which was co-segregated with the PKD phenotype in the family.RT-PCR and direct sequencing of amplified products revealed that this heterozygous synonymous mutation led to exon7 skipping in PKD2 gene.Conclusion:We reported an extremely rare child case of ADPKD2 in combination with solitary kidney and nephrotic-range proteinuria,and firstly confirmed the pathogenicity of a heterozygous synonymous mutation(c.1716G>A)in PKD2 gene.The results indicate that synonymous mutations should not be excluded from disease-causing if they are located in splicing site of an exon.

Autosomal dominant tubulointerstitial kidney disease with a novel heterozygous missense mutation in the uromodulin gene: A case report

BACKGROUND Autosomal dominant tubulointerstitial kidney disease(ADTKD)is a progressive chronic disease that is inherited in an autosomal dominant fashion.Symptoms include hyperuricemia,gout,interstitial nephritis,renal cysts,and progressive renal damage that can lead to end-stage renal disease.Mutations in the uromodulin gene(UMOD)characterize the ADTKD-UMOD clinical subtype of this disease.To date,>100 UMOD mutations have been identified.Early diagnosis of ADTKD-UMOD is important to treat the disease,slow down disease progression,and facilitate the identification of potentially affected family members.CASE SUMMARY We report a 40-year-old man harboring a novel heterozygous missense mutation in UMOD(c.554G>T;p.Arg185Leu).The patient had hyperuricemia,gout,and chronic kidney disease.The same mutation was detected in his daughter,aunt and cousin.CONCLUSION A single nucleotide substitution in exon 3 of UMOD was responsible for the heterozygous missense mutation(c.554G>T,p.Arg185Leu).

Successful endoscopic surgery for emphysematous pyelonephritis in a non-diabetic patient with autosomal dominant polycystic kidney disease: A case report

BACKGROUND Emphysema pyelonephritis(EPN)is a very dangerous type of urinary tract infection.It is a lethal disease that develops rapidly and causes the patient to deteriorate rapidly,and it can easily lead to systemic infections and even sepsis.The incidence is extremely low,and it is prevalent in patients with diabetes.We here report a case of EPN in a non-diabetic patient with autosomal dominant polycystic kidney disease(ADPKD).We share the diagnosis and treatment procedure for this extremely rare condition to make this disease easier to identify and address early.CASE SUMMARY A 47-year-old woman presented to the emergency department of our hospital with a high fever and left back pain lasting 4 d.She had a history of autosomal dominant polycystic kidney and polycystic liver.She was diagnosed with left type I EPN and her vital signs deteriorated so quickly that she underwent an emergency operation in which a D-J tube was inserted into her left ureter on the second day after admission.Two months later,she underwent a second-stage flexible ureteroscopy and lithotripsy.Despite postoperative sepsis,she finally recovered after active symptomatic support treatment and effective anti-infective treatment.CONCLUSION Although EPN is more likely to occur in diabetic patients,for non-diabetic patients with ADPKD and upper urinary tract obstruction,the disease also causes rapid deterioration.Early and accurate diagnosis and timely removal of the obstruction by invasive means may be able to save the damaged kidney and the patient’s life.

Tolvaptan ameliorated kidney function for one elderly autosomal dominant polycystic kidney disease patient: A case report

BACKGROUND Polycystic kidney disease(PKD)is a genetic disorder characterized by the growth of numerous cysts within the kidneys.Disease progress of some patients often occurs at the early stage.Thus,managing and controlling disease progress is important to slow the kidney function decline especially for the patient with other disorders.CASE SUMMARY One 80-year-old male autosomal dominant polycystic kidney disease(ADPKD)patient with chronic kidney disease and other clinical disorders was treated with tolvaptan and edoxaban.Estimated glomerular filtration rate,creatinine and uric acid were monitored during the treatment.In addition,the whole exome sequencing was performed to screen ADPKD genetic variants.The kidney function decline was prevented after using tolvaptan and edoxaban treatment and in the meantime,a venous thromboembolism was removed and leg and pedal edema were alleviated.One mutation c.10102G>A/p.D3368N in the PKD1 gene was identified.CONCLUSION Tolvaptan combined with edoxaban administration could delay kidney function decline and eliminate the edema caused by the thromboembolism.

Spontaneous coronary dissection should not be ignored in patients with chest pain in autosomal dominant polycystic kidney disease:A case report

BACKGROUND When autosomal dominant polycystic kidney disease(ADPKD)presents with acute coronary syndrome(ACS),the possibility of spontaneous coronary artery dissection(SCAD)should be highly considered.In some cases,SCAD is considered an extrarenal manifestation of ADPKD depending on the pathological characteristics of the unstable arterial wall in ADPKD.CASE SUMMARY Here,we report a 46-year-old female patient with ADPKD who presented with ACS.Coronary angiography revealed no definite signs of dissection,while intravascular ultrasound revealed a proximal to distal dissection of the left circumflex.After a careful conservative medication treatment,the patient exhibited favorable prognosis.CONCLUSION In cases of ADPKD co-existing with ACS,differential diagnosis of SCAD should be considered.Moreover,when no clear dissection is found on coronary angiography,IVUS should be performed to prevent missed diagnosis.

Acute Effects of Tolvaptan on Renal Hemodynamics in Autosomal Dominant Polycystic Kidney Disease —A Randomized, Cross-Over, Double Blind, Placebo-Controlled Study of Renal Plasma Flow and Glomerular Filtration Rate

Background: Previous studies have shown that reduced renal plasma flow (RPF) may play a role in progression of renal disease in autosomal dominant polycystic kidney disease (ADPKD). Tolvaptan, a vasopressin 2 antagonist, reduces growth of total kidney volume and slows the decrease in estimated glomerular filtration rate (eGFR) in ADPKD. The purpose of this randomized, cross-over, double-blind, placebo-controlled study was to investigate if acute tolvaptan treatment increases RPF in ADPKD patients. Methods: Eighteen ADPKD patients (chronic kidney disease stages I-III) were investigated twice (min. 10 days apart) after acute treatment with either tolvaptan 60 mg or placebo. Two hours after treatment RPF and GFR were estimated by Technetium-99m diethylenetriamine penta-acetic acid (99-mTc-DTPA) renography. During the examination day, central and brachial blood pressures (BP) were measured using Mobil-O-Graph? PWA. We also measured plasma concentrations of vasopressin (p-AVP), renin (PRC), angiotensin II (p-AngII) and aldosterone (p-Aldo), urine excretion of aquaporin 2 (u-AQP2), urine output (OU), urine osmolality (u-Osm) and fractional excretion of sodium (FENa). Results: 99-mTc-DTPA renography showed a similar RPF (673 ± 262 ml/min after tolvaptan vs. 650 ± 209 ml/min after placebo, p = 0.571) and GFR (78 ± 26 ml/min after tolvaptan vs. 79 ± 21 ml/min after placebo p = 0.774) after tolvaptan and placebo treatment. P-AVP and UO increased and u-Osm decreased after tolvaptan and remained unchanged during placebo. Systolic BP tended to decrease during renography during tolvaptan. Very small or insignificant changes were seen in PRC, p-AngII and p-Aldo. Conclusions: Acute tolvaptan treatment did not change renal hemodynamics in ADPKD.

Simultaneous nephrectomy during kidney transplantation for polycystic kidney disease does not detrimentally impact comorbidity and graft survival

BACKGROUND The lack of space,as an indication for a native unilateral nephrectomy for positioning a future kidney graft in the absence of other autosomal dominant polycystic kidney disease-related symptoms,remains controversial.AIM To evaluate the surgical comorbidity and the impact on graft survival of an associated ipsilateral native nephrectomy during isolated kidney transplantation in patients with autosomal dominant polycystic kidney disease.METHODS One hundred and fifty-four kidney transplantations performed between January 2007 and January 2019 of which 77 without(kidney transplant alone(KTA)group)and 77 with associated ipsilateral nephrectomy(KTIN group),were retrospectively reviewed.Demographics and surgical variables were analyzed and their respective impact on surgical comorbidity and graft survival.RESULTS Creation of space for future graft positioning was the main reason(n=74,96.1%)for associated ipsilateral nephrectomy.No significant difference in surgical comorbidity(lymphocele,wound infection,incisional hernia,wound hematoma,urinary infection,need for blood transfusion,hospitalization stay,Dindo Clavien classification and readmission rate)was observed between the two study groups.The incidence of primary nonfunction and delayed graft function was comparable in both groups[0%and 2.6%(P=0.497)and 9.1%and 16.9%(P=0.230),respectively,in the KTA and KTIN group].The 1-and 5-year graft survival were 94.8%and 90.3%,and 100%and 93.8%,respectively,in the KTA and KTIN group(P=0.774).The 1-and 5-year patient survival were 96.1%and 92.9%,and 100%and 100%,respectively,in the KTA and KTIN group(P=0.168).CONCLUSION Simultaneous ipsilateral native nephrectomy to create space for graft positioning during kidney transplantation in patients with autosomal dominant polycystic kidney disease does not negatively impact surgical comorbidity and short-and long-term graft survival.

Research on autosomal dominant polycystic kidney disease in China

Objective To review the history and recent development of research on autosomal dominant polycystic kidney disease （ADPKD） in China. Data sources Both Chinese and English literatures were searched in MEDLINE/CD ROM （1979 - 2006） and the Chinese Biomedical Literature Disk （1979 - 2006）. Study selection Published articles about ADPKD from mainland of China were selected. Data were mainly extracted from 58 articles which are listed in the reference section of this review. Results Some preliminary reports on cyst decompression surgeries and mutation analysis represent the contribution to the ADPKD research from China in the history. A serial of basic research and clinical studies on ADPKD in recent years also have been summarized. A technique platform for ADPKD research was firstly established. The genomics/proteomics/bioinformatics approach was introduced, which provide a lot of valuable information for understanding the pathogenesis. By denature high performance liquid chromatography （DHPLC） technique the entire PKD1 and PKD2 gene sequence screening system for Chinese Han population has been successfully established. Based on the characteristic data of Chinese patients, an integrated therapy protocol was put forward and won an advantage over the traditional therapy. Some novel experimental studies on therapy also were encouraging. Condusions Remarkable progress of ADPKD research in China have been made recently. Still many works, including the government support, international collaboration and active participation of more Chinese nephrologists, should be enhanced to advance this process in the near future.

The genetic framework for development of nephrolithiasis

Over 1%-15% of the population worldwide is affected by nephrolithiasis,which remains the most common and costly disease that urologists manage today.Identification of atrisk individuals remains a theoretical and technological challenge.The search for monogenic causes of stone disease has been largely unfruitful and a technological challenge;however,several candidate genes have been implicated in the development of nephrolithiasis.In this review,we will review current data on the genetic inheritance of stone disease,as well as investigate the evolving role of genetic analysis and counseling in the management of nephrolithiasis.

Transarterial Embolization for Treatment of Symptomatic Polycystic Liver Disease： More than 2-year Follow-up

Background： Currently, treatment of symptomatic polycystic liver disease （PLD） is still a challenging problem, especially for these patients who are not feasible for surgery. Minimally invasive options such as laparoscopic fenestration and percutaneous cyst aspiration with sclerotherapy demonstrated disappointing results due to multiple lesions. Because the cysts in PLD are mostly supplied from hepatic arteries but not from portal veins, transcatheter arterial embolization （TAE） of the hepatic artery branches that supply the major hepatic cysts can lead to shrinkage of the cyst and liver size, relieve symptoms, and improve nutritional status. This study aimed to evaluate the effectiveness of TAE with a mixture of N-butyl-2-cyanoacrylate （NBCA） and iodized oil for patients with severe symptomatic PLD during a more than 2-year follow-up, Methods： Institutional review board had approved this study. Written informed consent was obtained from all patients. From February 2007 to December 2014, twenty-three patients （20 women and 3 men; mean age, 49.0 ± 14.5 years） infeasible for surgical treatments underwent TAE. Changes in the abdominal circumferences, volumes of intrahepatic cysts, hepatic parenchyma volume, and whole liver, clinical symptoms, laboratory data, and complications were evaluated after TAE. Results： Technical success was achieved in all cases. No procedure-related major complications occurred. The median follow-up period after TAE was 48.5 months （interquartile range, 30.0-72.0 months）. PLD-related severe symptoms were improved remarkably in 86% of the treated patients; TAE failed to benefit in four patients （four patients did not benefit from TAE）. The mean maximum abdominal circumference decreased significantly from 1 06.0± 8.0 cm to 87.0 ± 15.0 cm （P = 0.021）. The mean intrahepatic cystic volume reduction rates compared with pre-TAE were 36% at 12 months, 37% at 24 months, and 38% at 36 months after TAE （P 〈 0.05）. The mean liver volume reduction rates were 32% at 12 months, 31% at 24 months, and 33% at 36 months （P 〈 0.05）. Conclusions： TAE with the mixture of NBCA and iodized oil appears to be a safe and effective treatment method for patients with symptomatic PLD, especially for those who are not good candidates for surgical treatments, to improve both hepatic volume and hepatic cysts volume.

Genetic Testing of the mucin I gene-Variable Number Tandem Repeat Single Cytosine Insertion Mutation in a Chinese Family with Medullary Cystic Kidney Disease

Background： Medullary cystic kidney disease （MCKD） is clinically indistinguishable from several other autosomal-dominant renal diseases： thus, molecular genetic testing is needed to establish a definitive diagnosis. A specific type of single cytosine insertion in the variable number tandem repeat （VNTR） of the mucin 1 （MUC1） gene is the only known cause of MCKD1; however, genetic analysis of this mutation is difficult and not yet offered routinely. To identify the causative mutation/s and establish a definitive diagnosis in a Chinese family with chronic kidney disease, clinical assessments and genetic analysis were performed, including using a modified genotyping method to identify the MUC1-VNTR single cytosine insertion. Methods： Clinical data from three patients in a Chinese family with chronic kidney disease were collected and evaluated. Linkage analysis was used to map the causative locus. Mutation analysis of uromodulin （UMOD） gene was performed using polymerase chain reaction （PCR） and direct sequencing. For MUC1 genotyping, the mutant repeat units were enriched by Mwol restriction, and then were amplified and introduced into pMD-18T vectors. The 192 clones per transformant were picked up and tested by colony PCR and second round of Mwol digestion. Finally, Sanger sequencing was used to confirm the MUC1 mutation. Results： Clinical findings and laboratory results were consistent with a tubulointerstitial lesion. Linkage analysis indicated that the family was compatible with the MCKDI locus. No mutations were found in UMOD gene. Using the modified MUC1 genotyping method, we detected the MUC1-VNTR single cytosine insertion events in three patients of the family; and mutation-containing clones were 12/192, 14/192, and 5/96, respectively, in the three patients. Conclusions： Clinical and genetic findings could support the MCKDI diagnosis. The modified strategy has been demonstrated to be a practical way to detect MUCI mutation.