Tesevatinib ameliorates progression of polycystic kidney disease in rodent models of autosomal recessive polycystic kidney disease

AIMTo investigate the therapeutic potential of tesevatinib （TSV）, a unique multi-kinase inhibitor currently in Phase Ⅱ clinical trials for autosomal dominant polycystic kidney disease （ADPKD）, in well-defined rodent models of autosomal recessive polycystic kidney disease （ARPKD）. METHODSWe administered TSV in daily doses of 7.5 and 15 mg/kg per day by I.P. to the well characterized bpk model of polycystic kidney disease starting at postnatal day（PN） 4 through PN21 to assess efficacy and toxicity in neonatal mice during postnatal development and still undergoing renal maturation. We administered TSV by oral gavage in the same doses to the orthologous PCK model （from PN30 to PN90） to assess effcacy and toxicity in animals where developmental processes are complete. The following parameters were assessed： Body weight, total kidney weight; kidney weight to body weight ratios; and morphometric determination of a cystic index and a measure of hepatic disease. Renal function was assessed by： Serum BUN; creatinine; and a 12 h urinary concentrating ability. Validation of reported targets including the level of angiogenesis and inhibition of angiogenesis （active VEGFR2/KDR） was assessed by Western analysis.RESULTSThis study demonstrates that： （1） in vivo pharmacological inhibition of multiple kinase cascades with TSV reduced phosphorylation of key mediators of cystogenesis： EGFR, ErbB2, c-Src and KDR; and （2） this reduction of kinase activity resulted in signifcant reduction of renal and biliary disease in both bpk and PCK models of ARPKD. The amelioration of disease by TSV was not associated with any apparent toxicity.CONCLUSIONThe data supports the hypothesis that this multi-kinase inhibitor TSV may provide an effective clinical therapy for human ARPKD.

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.

Current management of autosomal dominant polycystic kidney disease

Autosomal dominant polycystic kidney disease （ADPKD）, the most frequent cause of genetic renal disease affecting approximately 4 to 7 million individuals worldwide and accounting for 7%-15% of patients on renal replacement therapy, is a systemic disorder mainly involving the kidney but cysts can also occur in other organs such as the liver, pancreas, arachnoid membrane and seminal vesicles. Though computed tomography and magnetic resonance imaging （MRI） were similar in evaluating 81% of cystic lesions of the kidney, MRI may depict septa, wall thickening or enhancement leading to upgrade in cyst classification that can affect management. A screening strategy for intracranial aneurysms would provide 1.0 additional year of life without neurological disability to a 20-year-old patient with ADPKD and reduce the fnancial impact on society of the disease. Current treatment strategies include reducing： cyclic adenosine monophosphate levels, cell proliferation and fluid secretion. Several randomised clinical trials （RCT） including mammalian target of rapamycin inhibitors, somatostatin analoguesand a vasopressin V2 receptor antagonist have beenperformed to study the effect of diverse drugs ongrowth of renal and hepatic cysts, and on deteriorationof renal function. Prophylactic native nephrectomy isindicated in patients with a history of cyst infection orecurrent haemorrhage or to those in whom space musbe made to implant the graft. The absence of largeRCT on various aspects of the disease and its treatmen leaves considerable uncertainty and ambiguity in many aspects of ADPKD patient care as it relates to end stage renal disease （ESRD）. The outlook of patients with ADPKD is improving and is in fact much better than that for patients in ESRD due to other causes. This review highlights the need for well-structured RCTs as a frst step towards trying newer interventions so as to develop updated clinical management guidelines.

Exome sequencing identifies compound heterozygous PKHD1 mutations as a cause of autosomal recessive polycystic kidney disease

Background Autosomal recessive polycystic kidney disease （ARPKD） is a rare inherited disease, which is a disorder with multiple organ involvement, mainly the kidney and liver. It is caused by mutations in the PKHD1 gene. Here, we reported the clinical characteristics of a case with ARPKD and analyze the genetic features of this patient as well as of his father using targeted exome sequencing and Sanger sequencing. Methods Genomic DNA was extracted from peripheral blood leukocytes obtained from a patient with ARPKD. The mutations were identified using exome sequencing and confirmed by Sanger sequencing. Results The patient was diagnosed as ARPKD based on ultrasonography and abdominal computed tomography which showed polycystic changes, multiple calcinosis of both kidneys, and multiple dilated bile ducts of the liver. Compound heterozygous PKHD1 gene mutations A979G and G5935A, which lead to substitution of an asparagine for an aspartate at amino acid 327 （N327D） and a glycine for an arginine at amino acid 1979 （G1979R） respectively, were identified using targeted exome sequencing and confirmed by Sanger sequencing for the patient. In addition, the father of the patient was identified to be a carrier of heterozygous A979G mutation of this gene. Conclusions We identified that the compound heterozygous PKHD1 gene mutations are the molecular basis of the patient with ARPKD. Targeted exome sequencing is suitable for genetic diagnosis of single-gene inherited diseases like ARPKD in which the pathogenic gene is a large.

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.

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.

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.

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.

Acute abdomen and ascites as presenting features of autosomal dominant polycystic kidney disease

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.

The Clinical Association of Autosomal Dominant Polycystic Kidney Disease and renal cell Carcinoma

Autosomal Dominant Polycystic Kidney Disease (ADPKD) is not currently considered to be a risk factor for renal cell carcinoma (RCC). We present data from our institution demonstrating incidence of RCC with ADPKD above the incidence rate for RCC in the general population, as well as that in patients with end-stage renal disease (ESRD). The discussion relates our findings in the context of the current literature including recent case reports published in this entity.

The Association between Autosomal Dominant Polycystic Kidney Disease and Renal Cell Carcinoma

Objectives: The relationship between autosomal dominant polycystic kidney disease (ADPKD) and renal cell carcinoma (RCC) is investigated to determine a link that would guide management due to elevated RCC risk. Current literature is inconclusive on this topic. Methods: This study is a retrospective chart review of patients having undergone nephrectomy. Those with pathology and history consistent with ADPKD were reviewed for presence of RCC. Results: The review at this institution revealed RCC in 18% of ADPKD patients who underwent nephrectomy. These rates are significantly higher than those found in the general population, and even greater than those would be expected in patients suffering end-stage renal disease (ESRD). Conclusions: Due to the increased prevalence of RCC in ADPKD, clinicians managing patients with ADPKD should maintain a high index of suspicion. Our data suggest a link between ADPKD and RCC, most likely at the genetic level. In light of this, we feel that further genetic research is needed to potentially discover the link between these two disease processes.

A Prospective Study on Clinical Profile of Autosomal Dominant Polycystic Kidney Disease (ADPKD) in Jammu for a Period of 1 Year

The Present Study was conducted in department of Medicine, Govt. Medical College, jammu, Where a total of 41 patients—29 males and 12 females—fulfilled the inclusion criteria of ADPKD, were gathered during the period of 1 year starting from Nov. 2011 to Oct. 2012. All the patients were subjected to a detailed history, clinical examination and laboratory investigations. X-ray chest (PA view), ECG and ultrasound of abdomen for kidneys, liver and spleen were done. Intravenous pyelogram and CT scan of abdomen was done when a definitive diagnosis of (ADPKD) could not be made on abdominal ultrasound. Echocardiography was done to evaluate cardiac murmurs and associated mitral valve prolapse, based on standard criteria. Male to female patients with ADPKD was 2.42:1. Maximum 17 (41.5%) patients of both gender were seen in 30 - 40 years age group, Family history of ADPKD was present in 18 (43.9%) patients;Hypertension, alone or in combination with renal failure, was present in 65.8% patients;Hypertension alone was present in 19 (46.3%) patients;8 (19.5%) patients with hypertension had renal failure;Low back pain was present in 24 (58.5%) and abdominal pain in 22 (53.7%) patients;15 (36.6%) patients presented with at least one episode of gross haematuria;Headache was experienced by 18 (43.9%) patients. On clinical examination, 24 (58.5%) were found to have palpable kidney and 10 (24.4%) had palpable liver. Spleen was palpable in 1 (2.4%) patient, Murmur of mitral valve prolapse was found in 2 (4.9%) Patients;3 (7.3%) patients having left ventricular hypertrophy;mean Hb was 11.2 g/dL. The liver cysts were found in 24.4% of the patients;Out of 10 (24.4%) patients with hepatic cyst involvement, 1 patient each was found to have evidence of portal hypertension and evidence of hepatic cyst infection. In the present study, hypertension was most common presentation of this disease. So, control of hypertension is very important to prevent progression of this disease. Patients who are detected to have ADPKD should be regularly followed-up to prevent further progression by timely intervention. Also, family members of patients should be screened for disease and initiate treatment as early as possible.

Role of calcium in polycystic kidney disease:From signaling to pathology

Autosomal dominant polycystic kidney disease （ADPKD） is the most common inherited monogenic kidney disease. Characterized by the development and growth of cysts that cause progressive kidney enlargement, it ultimately leads to end-stage renal disease. Approximately 85% of ADPKD cases are caused by mutations in the PKD1 gene, while mutations in the PKD2 gene account for the remaining 15% of cases. The PKD1 gene encodes for polycystin-1 （PC1）, a large multi-functional memb-rane receptor protein able to regulate ion channel complexes, whereas polycystin-2 （PC2）, encoded by the PKD2 gene, is an integral membrane protein that functions as a calcium-permeable cation channel, located mainly in the endoplasmic reticulum （ER）. In the primary cilia of the epithelial cells, PC1 interacts with PC2 to form a polycystin complex that acts as a mechanosensor, regulating signaling pathways involved in the differentiation of kidney tubular epithelial cells. Despite progress in understanding the function of these proteins, the molecular mechanisms associated with the pathogenesis of ADPKD remain unclear. In this review we discuss how an imbalance between functional PC1 and PC2 proteins may disrupt calcium channel activities in the cilium, plasma membrane and ER, thereby altering intracellular calcium signaling and leading to the aberrant cell proliferation and apoptosis associated with the development and growth of renal cysts. Research in this feld could lead to the discovery of new molecules able to rebalance intracellular calcium, thereby normalizing cell proliferation and reducing kidney cyst progression.

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.

Peritoneal dialysis for autosomal dominant polycystic kidney disease: a retrospective study

To describe the long-term clinical outcomes of patients with autosomal dominant polycystic kidney disease （ADPKD） who are on peritoneal dialysis （PD） therapy. We performed a retrospective matched-cohort analysis com- paring the clinical outcomes of 30 ADPKD patients with those of 30 non-diabetic patients who had bilateral small kidneys between July 1 2007 and July 31 2014. The patient groups were matched by age, gender, and time of PD initiation. There were no significant differences in the demographic or biochemical parameters, comorbid conditions, residual glomerular filtration rate, or Charison comorbidity score at the beginning of PD. The median renal volume was 1315 ml for the ADPKD group and 213 ml for the control group. Patients with ADPKD had similar 3-year patient survival （90.6% versus 86.3%, ,~=-0.807） and technique survival （89.2% versus 74.3%, P=0.506） compared with non-ADPKD patients. Also, there was no significant difference in the peritonitis-free survival between the ADPKD and control groups （P=0.22）, and rates of peritonitis were similar （0.19 versus 0.21 episodes per patient-year, P=-0.26）. No differences were observed in the incidence of PD-related complications, such as hernia and dialysate leak. ADPKD is not a con- traindication for PD, and a subgroup of ADPKD patients with relatively small kidney volume can be treated using PD.

2例围生期型常染色体隐性多囊肾病家系的PKHD1基因变异分析

目的对2例常染色体隐性多囊肾病(autosomal recessive polycystic kidney disease,ARPKD)家系进行基因变异分析,明确致病原因,为ARPKD的早期诊断、治疗、遗传咨询及产前诊断提供理论依据。方法收集2例胎儿引产组织及父母外周血进行全外显子测序分析,结合Sanger测序进行家系分析及位点验证。结果全外显子组测序及Sanger测序提示家系1胎儿PKHD1基因存在c.3436C>T(p.Q1146X)和c.1981A>C(p.T661P)复合杂合变异;家系2曾生育1例ARPKD患儿,1岁时死于心力衰竭,本例胎儿PKHD1基因存在c.9719G>A(p.R3240Q),c.10057C>T(p.L3353F)和c.7237C>T(p.R2413C)复合杂合变异。结论两个家系均为PKHD1基因变异导致的围生期型ARPKD,共发现5个基因变异位点,其中2个为新发变异位点,c.10057C>T和c.1981A>C均为错义变异。鉴于ARPKD基因型和表型的复杂性,及早进行家系的遗传咨询将有助于基因诊断和早期产前诊断。