Abdominal sonographic study of autosomal dominant polycystic kidney disease

PURPOSE: The purpose of this study was to determine whether kidney size in patients who have autosomal dominant polycystic kidney disease (ADPKD) is related to renal function, hypertension, or extrarenal manifestations of the disease and to sonographically evaluate the abdominal manifestations of ADPKD. METHODS: Between 1994 and 1998, 400 individuals from 85 families with a history of ADPKD were examined. There were 213 persons with ADPKD and 187 unaffected family members; there were 182 males and 218 females, 1-82 years old (mean, 39.3 years). We obtained a complete medical history, performed a physical examination, measured the arterial blood pressure and serum creatinine levels, and performed abdominal sonography on each subject. The sonographic features that were studied were renal length and the presence and number of cysts on the kidneys, liver, and pancreas. RESULTS: There was a relationship between kidney size and age (p < 0.05), kidney size and renal function (p < 0.001), and kidney size and hypertension (p < 0.001). The overall prevalence of hepatic cysts in patients with ADPKD was 67%, and the prevalence increased with age. The presence of hepatic cysts was related to the severity of renal disease. Females had more severe polycystic liver disease, and massive polycystic liver disease (ie, hepatomegaly with innumerable cysts) was seen only in females. The prevalence of pancreatic cysts in the 187 persons in whom the pancreas was well evaluated sonographically was 5%. CONCLUSIONS: Kidney size in patients with ADPKD is related to renal function, hypertension, and extrarenal involvement and can be used to predict the outcome of the disease. Hepatic cysts are very common in patients with ADPKD and are related to age and renal function; pancreatic cysts are infrequent in these patients.     

Expression and cellular localisation of renal endothelin-1 and endothelin receptor subtypes in autosomal-dominant polycystic kidney disease

The major factors influencing the rate of progression of chronic renal disease in autosomal-dominant polycystic kidney disease (ADPKD) are unknown and there are currently no effective treatments for slowing the progression of chronic renal failure in ADPKD patients. As a first step in investigating the potential role of endothelin-1 (ET1) and its receptors (ETA and ETB) in the pathophysiology of progression in ADPKD, we have studied their expression and cellular localisation in ADPKD kidney. Immunoreactive ET1 was detected in cyst epithelia, mesangial cells and vascular smooth muscle cells suggesting continuing ET1 synthesis in the cystic kidney. Compared to healthy controls, ETA mRNA was 5-10-fold higher in ADPKD cystic kidney. In cystic kidney, neo-expression of ETA receptors was found overlying glomeruli and cysts and markedly increased in medium-sized renal arteries by microautoradiography. This is the first study to demonstrate a specific upregulation of ETA receptors in human renal disease. Future studies should address whether ETA selective antagonists may be effective in slowing renal disease progression in ADPKD.     

Effect of statin therapy on disease progression in pediatric ADPKD: design and baseline characteristics of participants

Autosomal dominant polycystic kidney disease (ADPKD) is the most common genetic kidney condition and is associated with important renal and cardiovascular manifestations in childhood. Renal cystic disease can be documented in some cases as early as in utero. Early intervention is critical if the long-term complications of this condition, including end-stage renal disease, are to be ameliorated. Here we describe our ongoing randomized double-blind placebo-controlled phase III clinical trial to assess the effect of pravastatin treatment on renal and cardiovascular disease progression in 107 children and young adults age 8-22 years with ADPKD who are receiving the angiotensin converting enzyme inhibitor lisinopril. Baseline demographic and laboratory data are provided. Results of this study could markedly impact the standard of care for evaluation and treatment of ADPKD in this population.     

Portal hypertension due to extensive hepatic cysts in autosomal dominant polycystic kidney disease.

Liver cysts are a well-recognized feature of autosomal dominant polycystic kidney disease (ADPKD) and occur in 77% of patients more than 60 years old. Serious sequelae, however, are rare, the two most common complications being pain and cyst infections. Portal hypertension has been reported in ADPKD due to the rare presence of congenital hepatic fibrosis. We report a case of ADPKD in a patient who had portal hypertension due to distortion of portal vein and venules by extensive hepatic cysts.     

Diagnosis of autosomal dominant polycystic kidney disease in utero and in the young infant

Autosomal dominant polycystic kidney disease (ADPKD), once thought to be a disease of the adult, is now being reported with increasing frequency in childhood. We report five cases and review eight cases from the literature of ADPKD diagnosed in the fetus or the young infant by sonographic evaluation and a positive family history. Renal enlargement (85%) was the most common and most helpful sonographic finding. Approximately 50% of the patients already had cysts large enough to detect by ultrasound. Increased renal echogenicity was present in nine of 10 cases. Although every case in this review had one parent affected with ADPKD, only five of 13 (38%) were aware of their disease prior to their pregnancy. Renal cystic disease diagnosed in the fetus and young infant should trigger an investigation of the family history and sonographic screening.     

Identification and localization of polycystin,the PKD1 gene product.

Polycystin, the product of autosomal dominant polycystic kidney disease (ADPKD) 1 gene (PKD1) is the cardinal member of a novel class of proteins. As a first step towards elucidating the function of polycystin and the pathogenesis of ADPKD, three types of information were collected in the current study: the subcellular localization of polycystin, the spatial and temporal distribution of the protein within normal tissues and the effects of ADPKD mutations on the pattern of expression in affected tissues. Antisera directed against a synthetic peptide and two recombinant proteins of different domains of polycystin revealed the presence of an approximately 400-kD protein (polycystin) in the membrane fractions of normal fetal, adult, and ADPKD kidneys. Immunohistological studies localized polycystin to renal tubular epithelia, hepatic bile ductules, and pancreatic ducts, all sites of cystic changes in ADPKD, as well as in tissues such as skin that are not known to be affected in ADPKD. By electron microscopy, polycystin was predominantly associated with plasma membranes. Polycystin was significantly less abundant in adult than in fetal epithelia. In contrast, polycystin was overexpressed in most, but not all, cysts in ADPKD kidneys.     

Chronic renal failure in a patient with Sotos syndrome due to autosomal dominant polycystic kidney disease

Sotos syndrome is characterised by accelerated growth, acromegalic appearance, mental retardation and social maladjustment. Most cases are sporadic, but familial cases have also been reported. We report a case of Sotos syndrome presenting with chronic renal failure due to autosomal dominant polycystic kidney disease (ADPKD). Ultrasonographic examination of the patient, his father and other family members revealed polycystic kidneys. Renal failure was present only in the Sotos case, who also had considerably larger cysts than other family members. We suggest that the underlying mechanism responsible from the somatic overgrowth in Sotos syndrome may also be linked with the development of larger cysts and earlier onset of renal failure in ADPKD. Although Sotos syndrome has been associated with urological abnormalities, chronic renal failure is very rare. To our knowledge, Sotos syndrome associated with ADPKD has not been reported before.     

Prenatal sonographic patterns in autosomal dominant polycystic kidney disease: a multicenter study.

OBJECTIVE: To determine whether a specific prenatal sonographic pattern can be identified for autosomal dominant polycystic kidney disease (ADPKD) and if so whether it would be helpful in orienting complementary analysis, properly counseling parents and adapting pregnancy management. METHODS: A retrospective multicenter study was conducted in four prenatal diagnostic centers. The records of fetuses with a prenatal ultrasound examination revealing abnormal kidneys and with a final diagnosis of ADPKD were analyzed. Ultrasound analysis included: amount of amniotic fluid, bladder size, renal length, presence or absence of renal cysts and size of renal pelves, and was focused on parenchyma echogenicity and status of corticomedullary differentiation. Postnatal follow-up was reviewed. RESULTS: Of the 27 patients included in the study, 25 had hyperechogenic renal cortex and 20 had hypoechogenic medulla resulting in increased corticomedullary differentiation (CMD). In six cases, the medulla was hyperechogenic leading to absent or decreased CMD. One patient had normal cortical echogenicity and CMD. Renal cysts were present during the prenatal period in four patients (at 22 weeks in one case and after 30 weeks in three cases). In 12 patients, the cysts appeared after birth (within the first 6 months of postnatal life in 10 cases and by the age of 1 year in two cases). Elevated blood pressure was observed in only two cases and moderate chronic renal failure in one case. CONCLUSION: We have described the sonographic presentation in fetuses with ADPKD: moderately enlarged hyperechogenic kidneys with increased CMD. Although not specific to ADPKD, these findings should prompt familial screening. Other prenatal sonographic features (absent or decreased CMD and cortical cysts) are less frequent.     

Peritoneoscopy in adult polycystic kidney disease: its diagnostic value.

The value of peritoneoscopy in the diagnosis of renal polycystic disease was tested in nine patients with adult polycystic disease and one with congenital hepatic fibrosis. The right kidney was visualized in all ten cases and the left in seven. Renal cysts were recognized by peritoneoscopy in eight of the ten patients. Factors impeding visualization of the kidneys and the cysts were: a) fixation of the splenic flexure of the colon; b) non-superficial renal cysts. Of six cases in which intravenous pyelography was not diagnostic, peritoneoscopy was positive in four. No correlation was found between the degree of hepatic and renal cystic involvement.     

Renal cystic diseases as a ciliopathy

Renal cystic disease is characterized by expansion of renal tubules. Abnormal cell proliferation and randomly oriented cell division angle are thought to induce cystic changes in renal tubules. Recent advancements have identified many of causative genes. Interestingly, those gene products are localized in cilia or centriole, suggesting that cilia have some role to control tubular diameter. Several systemic syndromes accompany renal cystic diseases, particularly nephronophthisis. To identify nephronophthisis related pathway will be a clue to understand mechanisms to develop not only renal cysts but also phenotypes associated with ciliopathies.     

Acquired renal cystic disease and its complications in continuous ambulatory peritoneal dialysis patients.

PURPOSE: To determine whether there is any difference in the prevalence of acquired cystic disease and malignancy of the kidney in patients on continuous ambulatory peritoneal dialysis (CAPD) and hemodialysis. DATA IDENTIFICATION: Relevant studies published from January 1983 to June 1991 were identified by manual search and MEDLINE search. STUDY SELECTION: We reviewed the studies in which acquired renal cystic disease and/or renal cell carcinoma developed in patients on CAPD. DATA EXTRACTION: Details of the prevalence of acquired cystic disease and renal malignancy as a complication of acquired cysts in CAPD patients were tabulated with the duration of treatment. RESULTS: Acquired cystic disease was observed in 195 of 425 CAPD patients (41.1%), which is comparable to the prevalence of 47.1% (520/1103) seen in hemodialysis patients. The overall prevalence of renal cell carcinoma accompanying acquired cystic disease in this series of CAPD patients was 2 of 375 (0.4%), which is comparable to the prevalence of 1.5% (17/1103) in hemodialysis patients. So far, eight other instances of renal cell carcinoma complicating acquired cystic disease in CAPD patients were described as case reports. Retroperitoneal bleeding due to the rupture of acquired cysts has been reported on a few occasions. CONCLUSION: In this review no differences were detected in the prevalence or severity of acquired renal cystic disease in patients treated with CAPD as compared with those on hemodialysis. Therefore, the incidence of complications associated with acquired cysts may also be the same for the two treatment modalities, although reports on such complications are rare.     

常染色体显性多囊肾病的预后评估及治疗

常染色体显性多囊肾病(autosomal dominant polycystic kidney disease, ADPKD)患病率为1‰~2‰, 属于罕见病, 临床主要表现为双侧肾囊肿且逐渐发展, 肾脏体积进行性增大, 肾功能逐步降低。PKD1基因突变约占81%, PKD2基因突变约占10.5%~22%。血管加压素(arginine vasopressin, AVP)和环磷酸腺苷(cyclic adenosine monophosphate, cAMP)信号通路在ADPKD囊肿发展过程中发挥重要作用。近年来发表的梅奥风险评估模型和PROPKD(predicting renal outcome in polycystic kidney disease)评分是ADPKD较好的预后评估模型, 已成为临床医生决策的重要依据。通过拮抗AVP受体, 抑制cAMP通路的托伐普坦已成为ADPKD首个特异治疗药物, 可有效抑制总肾脏体积的增长和保护肾功能。药物的长期安全性仍需进一步研究。     

Autosomal dominant polycystic kidney disease: recent advances in pathogenesis and treatment

Autosomal dominant polycystic kidney disease (ADPKD) is a common genetic disorder affecting 1 in 1,000 people in the general population and accounts for up to 10% of all patients on renal replacement therapy. Numerous fluid-filled epithelial cysts arise from different nephron segments as spherical dilatations or small out-pouchings, enlarge progressively and eventually become disconnected from the rest of the renal tubule. The development of cysts is accompanied by destruction of the renal parenchyma, interstitial fibrosis, cellular infiltration and loss of functional nephrons. ADPKD is not only a kidney disease but also a systemic disorder associated with intracranial arterial aneurysms, cardiac valvular defects, colonic diverticulosis and cyst formation in other organs such as the liver, spleen and pancreas. The identification of PKD1 and PKD2 together with the drive to elucidate the functions of their encoded proteins, polycystin-1 (PC1) and polycystin-2 (PC2), has led to an explosion of clinical and scientific interest in this common disorder. The aim of this review is to highlight recent advances in our understanding of ADPKD pathogenesis which are leading to exciting new treatment strategies.     

Improving recognition of inherited renal disease

Polycystic kidney disease and Alport's syndrome are the most common causes of inherited renal disease in the UK. An average GP practice is likely to have at least six patients with autosomal dominant polycystic kidney disease (ADPKD). The disorder is characterised by the formation of fluid-filled cysts in the kidneys resulting in progressive renal impairment. Mutations in two genes have been identified. The PKD1 gene abnormality is responsible for 85% of cases of ADPKD, patients with PKD2 mutations typically present later and progress more slowly. Patients with ADPKD can present with a positive family history, hypertension, flank pain, haematuria, renal insufficiency or proteinuria. The diagnosis has traditionally been based on ultrasound imaging. Screening will reduce the incidence of a late diagnosis when renal disease is advanced but a normal ultrasound scan in those under 30 years old is not conclusive. It is not recommended that children are screened. The key to minimising the rate of progressive disease is tight BP control. ACE inhibitors are recommended as the initial antihypertensive agent unless contraindicated. Alport's syndrome is a disorder characterised by abnormal type IV collagen which is found in the kidney, eyes, skin and ears. Around one in ten practices are likely to have a patient with Alport's syndrome. Eighty per cent of patients have the X-linked form of the disease. All first-degree relatives of a patient with confirmed Alport's syndrome should be offered screening. The combination of reduced hearing and urinary abnormalities in a young boy should alert GPs to consider this as a possible diagnosis and initiate referral. Diagnosis can be confirmed by renal or skin biopsy.     

Long-term Medical Management of the Liver Transplant Recipient: What the Primary Care Physician Needs to Know

Recognition, management, and prevention of medical complications and comorbidities after liver transplant is the key to improved long-term outcomes. Beyond allograft-related complications, metabolic syndrome, cardiovascular disease, renal dysfunction, and malignancies are leading causes of morbidity and mortality in this patient population. Primary care physicians have an important role in improving outcomes of liver transplant recipients and are increasingly relied on for managing these complex patients. This review serves to assist the primary care physician in the long-term management issues of liver transplant recipients.     

CT与SPECT在常染色体显性多囊肾治疗中的应用

目的 探讨CT与SPECT在常染色体显性多囊肾(ADPKD)治疗中的作用.方法 回顾性分析89例ADPKD患者的病历资料,观察各期患者术前CT表现特点及术前、术后SPECT肾动态显像的变化.结果 患者术前CT显示双肾体积增大,肾实质内多发大小不等的囊性低密度影,增强扫描后肾盂与囊肿对比明显.SPECT肾动态显像结果显示Ⅰ、Ⅱ、Ⅲ期患者术前肾小球滤过率(GFR)分别为(49.47±9.93)ml/min、(30.59±8.16)ml/min、(14.84±6.22)ml/min,术后分别为(52.14±8.67)ml/min、(43.77±9.33)ml/min、(14.65±5.61)ml/min.Ⅱ期患者术后GFR显著高于术前(P<0.05),Ⅰ、Ⅲ期患者术后GFR与术前相比,差异无统计学意义(P>0.05).结论 联合应用CT及SPECT有利于掌握肾脏形态及功能的综合信息,选择最佳手术时机及合理治疗方案.     

High-resolution ultrasonography in the differential diagnosis of cystic diseases of the kidney in infancy and childhood: preliminary experience

Autosomal recessive polycystic kidney disease, autosomal dominant polycystic disease, and glomerulocystic disease may all appear in the perinatal period as bilaterally enlarged echogenic kidneys. Current ultrasonographic equipment can better demonstrate the underlying pathologic state and assist in the differentiation of these conditions. The primary abnormality in autosomal recessive polycystic kidney disease is at the level of the collecting ducts, which are dilated and saccular. The nephrons remain normal. These dilated ectatic tubules are seen in their usual distribution as a radial array, with major ducts being perpendicular to the renal capsule, in both the renal cortex and the medulla. The peripheral renal cortex does not normally contain collecting ducts and remains unaffected in patients with mild disease. Autosomal dominant polycystic disease is characterized by cystic changes involving both the nephron and the collecting ducts. The nephron may become cystic at any point. Multiple discrete cysts of varying sizes are seen in both the renal cortex and the medulla in the severely affected infant. Subcapsular cysts are seen regularly. Glomerulocystic disease is an unusual sporadic condition characterized by the cystic dilation of the space of Bowman and the proximal convoluted tubule. On ultrasonographic examination tiny, isolated cysts, usually smaller than those occurring in autosomal dominant polycystic kidney disease, are seen in the echogenic renal cortex and may extend to the periphery of the kidney. No cysts are seen in the renal medulla. Correlation between pathologic findings and sonographic images is of value in correctly diagnosing these conditions.     

Localized cystic disease of the kidney: CT findings

Background: We assessed the clinical and computed tomographic (CT) features of localized cystic disease of the kidney and how these features differentiate this disease from other renal cystic diseases. Methods: Medical records and CT scans of seven patients with localized cystic disease were reviewed retrospectively. Pathologic confirmation in five patients was done by surgery. The subjects consisted of four males and three females, with an age range of 29–74 years. Results: Localized cystic disease in five patients was an incidental finding. Clinical presentations in the other two patients included dark urine color, palpable flank mass, and generalized weakness. There was no patient with impairment of renal function associated with renal cystic disease. Six patients had cystic renal lesions in the left kidneys, and one patient had lesions in the right kidney. Six patients had cysts in a localized area in the affected kidney, and the remaining patient had diffuse involvement of the entire kidney. The upper pole was most frequently involved. CT appearance was characterized by multiple, variable size cysts conglomerated to islets of cysts that were separated by the normal renal parenchymal band. Conclusion: Localized cystic disease of the kidney has characteristic CT findings that distinguish it from other renal cystic diseases, making follow-up without surgical intervention possible.     

Book reviews

Background: We assessed the clinical and computed tomographic (CT) features of localized cystic disease of the kidney and how these features differentiate this disease from other renal cystic diseases. Methods: Medical records and CT scans of seven patients with localized cystic disease were reviewed retrospectively. Pathologic confirmation in five patients was done by surgery. The subjects consisted of four males and three females, with an age range of 29–74 years. Results: Localized cystic disease in five patients was an incidental finding. Clinical presentations in the other two patients included dark urine color, palpable flank mass, and generalized weakness. There was no patient with impairment of renal function associated with renal cystic disease. Six patients had cystic renal lesions in the left kidneys, and one patient had lesions in the right kidney. Six patients had cysts in a localized area in the affected kidney, and the remaining patient had diffuse involvement of the entire kidney. The upper pole was most frequently involved. CT appearance was characterized by multiple, variable size cysts conglomerated to islets of cysts that were separated by the normal renal parenchymal band. Conclusion: Localized cystic disease of the kidney has characteristic CT findings that distinguish it from other renal cystic diseases, making follow-up without surgical intervention possible.