Morbidity from Congenital Hepatic Fibrosis after Renal Transplantation for Autosomal Recessive Polycystic Kidney Disease

Presentation of autosomal recessive polycystic kidney disease (ARPKD) ranges from severe renal impairment and a high mortality rate in infancy to older children and adolescents with minimal renal disease and complications of congenital hepatic fibrosis (CHF), cholangitis and portal hypertension. Renal transplantation improves prognosis but it is unclear whether CHF in transplanted children follows the same clinical course as in older children with less severe renal disease. The aim of this study was to evaluate morbidity from CHF in ARPKD post renal transplantation. Data were analyzed for six males and eight females, transplanted for ARPKD (mean age 8.3 years, range 1-22.3 years) at the University of Minnesota between 1972 and 1998. Follow-up was for a mean of 14.5 years (range 3.1-33.6 years). One and 5 years patient survival rates were 93% and 86%, respectively. Overall five patients (36%) died; 4/5 deaths were related to CHF. Causes of death were hepatic failure immediately post transplant (n = 1), septicemia related to bile duct dilatation (n = 3) and multiorgan failure (n = 1). One and 5years graft survival rates were 87% and 70%, respectively. One patient had a combined liver-kidney transplant and two were re-transplanted. Initial signs of CHF were splenomegaly (n = 5), hepatosplenomegaly (n = 4) and gastrointestinal bleed (n = 2). Progression of CHF through childhood included hypersplenism (n = 7), esophageal varices with gastrointestinal bleeding (n = 5) and bile duct dilatation (n = 5). Portal hypertension was treated with portosystemic shunt (n = 3), sclerotherapy (n = 2), banding of varices (n = 1) and transjugular intrahepatic portosystemic shunt (n = 1). Of the nine survivors (mean age 12.8 years) 78% have functioning grafts (one liver-kidney transplant), 63% have portal hypertension and 22% have asymptomatic biliary dilatation. Complications of CHF developed in 79% of children who received a renal transplant for ARPKD. Mortality related to CHF occurred in 29% and accounted for 80% (4/5) of the deaths.     

The Effect of Smoking on Endothelial Dysfunction in Autosomal Dominant Polycystic Kidney Disease Patients with Preserved Renal Function

BackgroundIn autosomal dominant polycystic kidney disease (ADPKD), endothelial dysfunction (ED) is common and occurs much earlier than kidney function impairment. The impact of smoking on ED in ADPKD patients has not been previously studied. The aim of this study was to investigate the potential contribution of smoking habits to ED and subclinical atherosclerosis in these patients.MethodsThis case-control study included 54 ADPKD patients with preserved renal function and 45 healthy control subjects. ED was assessed using ischemia-induced forearm flow-mediated dilatation (FMD). Carotid intima-media thickness (CIMT) was measured from 10 mm proximal to the right common carotid artery. Clinical demographic characteristics and laboratory data were recorded for the patients and control group. Regression analysis was used to determine independent associations of ED and CIMT.ResultsFMD was significantly lower in the ADPKD patients (19.5 ± 5.63 vs. 16.56 ± 6.41, p = .018). Compared with nonsmoker ADPKD patients, smoker patients had significantly lower FMD values (18.19 ± 6.52 vs. 13.79 ± 5.27, p = .013). In multiple regression analysis, age (β = –0.294, 95% CI: −0.392: −1.96, p = .001) for FMD and smoking (β  =  1.328, 95% CI: 0.251, 2.404, p = .017) for CIMT were independent predictors.ConclusionsPatients with ADPKD had more impaired endothelial function and subclinical atherosclerosis compared with control subjects. Smoking may increase the risk of subclinical atherosclerosis in ADPKD patients.     

Native Nephrectomy in Renal Transplant Recipients With Autosomal Dominant Polycystic Kidney Disease

Introduction

Patients with autosomal dominant polycystic kidney disease (ADPKD) represent about 10% of kidney transplant recipients (KTR) and have unique needs regarding acceptance for this procedure. Whether native kidney nephrectomy (NKN) affects kidney transplantation (KT) outcomes remains a matter of debate, and more data is needed to establish a standard approach to KTR with ADPKD.

Adrenal Insufficiency Due to Isolated Adrenocorticotropin Deficiency Complicated by Autosomal Recessive Polycystic Kidney Disease

We describe a 29-old-year Japanese man with autosomal recessive polycystic kidney disease who was frequently hypoglycemic. Insulinoma as a cause of hypoglycemia was denied because the ratio of plasma immunoreactive insulin to glucose was low. Adrenal insufficiency was diagnosed because of the low urinary excretion of 17-hydroxycorticosteroids, and both blunted responses of plasma cortisol to an intravenous injection of adrenocorticotropin and of plasma adrenocorticotropin to an intravenous injection of human corticotropin releasing hormone were observed, although basal plasma concentrations of cortisol and adrenocorticotropin were normal. The elusion profile of plasma sample from our patient chromatographed on a Sephadex G-75 column showed two peaks of (1-39)-ACTH and β-lipotropin, with no evidence of high molecular weight form of ACTH. The plasma concentrations of thyroid stimulating hormone and growth hormone were within the normal range. These findings indicated that this patient with autosomal recessive polycystic kidney disease was associated with adrenal insufficiency due to isolated adrenocorticotropin deficiency.     

肾脏体积指标在监测成人型多囊肾病病情进展中的应用

成人型多囊肾病又称常染色体显性遗传性多囊肾病(ADPKD)是最常见的单基因遗传性肾病,发病率约为1/1000～1/500[1,2].     

Improvement of Endothelial Dysfunction with Simvastatin in Patients with Autosomal Dominant Polycystic Kidney Disease

Cardiovascular problems are a major cause of morbidity and mortality in patients with autosomal dominant polycystic kidney disease (ADPKD). Endothelial dysfunction (ED), which is an early manifestation of vascular injury, has been shown in patients with ADPKD. Statins have a beneficial effect in the reversal of ED. The aim of this study was to investigate the effects of a statin, simvastatin, on ED in patients with ADPKD. Sixteen patients with ADPKD having well-preserved renal function were included in the study. Endothelial function of the brachial artery was evaluated by using high-resolution vascular ultrasound. Endothelial-dependent dilatation (EDD) was expressed as the percentage change in the brachial artery diameter from baseline to reactive hyperemia. After the baseline evaluations of EDDs, patients were started treatment with simvastatin at a dose of 40 mg/day and were treated for six months. EDDs were recalculated after one and six months of therapy. Interleukin-6 (IL-6) and high-sensitivity C-reactive protein were also measured as markers of inflammation. Baseline EDD was 11.3 ± 6.9% in patients with ADPKD. After one month of simvastatin treatment, EDD increased significantly to 14.6 ± 4.6 % (P = 0.016 versus baseline). Endothelial-dependent dilatation further increased significantly to 18.9 ± 7.5 % (P = 0.011 versus baseline, P = 0.048 versus first month) after six months of therapy. There was also a significant decrease in the level of IL-6 from 21.6 ± 21.7 pg/mL to 9.1 ± 3.5 pg/mL (P= 0.002).

Six months of simvastatin therapy resulted in a significant improvement of ED in patients with ADPKD. This finding may be in part related to the pleiotropic effects of simvastatin.     

Ambulatory Blood Pressure and Endothelial Dysfunction in Patients with Autosomal Dominant Polycystic Kidney Disease

Cardiovascular problems are a major cause of morbidity and mortality in patients with autosomal dominant polycystic kidney disease (ADPKD). Endothelial dysfunction (ED), which is an early manifestation of vascular injury, has been shown in patients with ADPKD. However, the association between ambulatory blood pressure and ED has not been investigated in these patients. Forty-one patients with ADPKD having well-preserved renal function were included in the study. Ambulatory blood pressure monitoring was performed in all patients. Patients were divided into dipper and non-dipper groups. Endothelial function of the brachial artery was evaluated by using high-resolution vascular ultrasound. Endothelial-dependent dilatation was expressed as the percentage change in the brachial artery diameter from baseline to reactive hyperemia. The mean 24-hour systolic blood pressure was similar in both groups (125.5 ± 10.7 mmHg in dippers and 121.2 ± 14.3 in non-dippers, p > 0.05). There was also no significant difference between the mean 24-hour diastolic blood pressures in both groups (82.3 ± 9.6 mmHg in dippers and 77.1 ± 8.6 mmHg in non-dippers, p > 0.05). The nocturnal fall rate in systolic blood pressure was 11.1 ± 1.2% in dippers and 0.98 ± 0.9% in non-dippers (p = 0.001). The nocturnal fall rate in diastolic blood pressure was 14.0 ± 0.9% in dippers and 3.8 ± 0.8% in non-dippers (p = 0.001). Endothelial-dependent dilatation was significantly higher in dippers compared to non-dippers (6.22 ± 4.14% versus 3.57 ± 2.52%, p = 0.025). Non-dipper patients with ADPKD show significant ED, which has an important impact on cardiovascular morbidity and mortality.     

mTOR抑制剂在ADPKD中的应用

常染色体显性多囊肾病(autosomal dominant polycystic kidney disease,ADPKD)是人类最常见的遗传性肾病,其发病率为0.1%～2.5%[1],就诊多见于成人,其临床表现主要有肾脏体积增大、血尿、蛋白尿、高血压.     

Imaging-Based Diagnosis of Autosomal Dominant Polycystic Kidney Disease

The clinical use of conventional ultrasonography (US) in autosomal dominant polycystic kidney disease (ADPKD) is currently limited by reduced diagnostic sensitivity, especially in at-risk subjects younger than 30 years of age. In this single-center prospective study, we compared the diagnostic performance of MRI with that of high-resolution (HR) US in 126 subjects ages 16–40 years born with a 50% risk of ADPKD who underwent both these renal imaging studies and comprehensive PKD1 and PKD2 mutation screening. Concurrently, 45 healthy control subjects without a family history of ADPKD completed the same imaging protocol. We analyzed 110 at-risk subjects whose disease status was unequivocally defined by molecular testing and 45 unaffected healthy control subjects. Using a total of >10 cysts as a test criterion in subjects younger than 30 years of age, we found that MRI provided both a sensitivity and specificity of 100%. Comparison of our results from HR US with those from a previous study of conventional US using the test criterion of a total of three or more cysts found a higher diagnostic sensitivity (approximately 97% versus approximately 82%) with a slightly decreased specificity (approximately 98% versus 100%) in this study. Similar results were obtained in test subjects between the ages of 30 and 40 years old. These results suggest that MRI is highly sensitive and specific for diagnosis of ADPKD. HR US has the potential to rival the diagnostic performance of MRI but is both center- and operator-dependent.     

Predictors of Autosomal Dominant Polycystic Kidney Disease Progression

Autosomal dominant polycystic kidney disease is a genetic disorder associated with substantial variability in its natural course within and between affected families. Understanding predictors for rapid progression of this disease has become increasingly important with the emergence of potential new treatments. This systematic review of the literature since 1988 evaluates factors that may predict and/or effect autosomal dominant polycystic kidney disease progression. Predicting factors associated with early adverse structural and/or functional outcomes are considered. These factors include PKD1 mutation (particularly truncating mutation), men, early onset of hypertension, early and frequent gross hematuria, and among women, three or more pregnancies. Increases in total kidney volume and decreases in GFR and renal blood flow greater than expected for a given age also signify rapid disease progression. Concerning laboratory markers include overt proteinuria, macroalbuminuria, and perhaps, elevated serum copeptin levels in affected adults. These factors and others may help to identify patients with autosomal dominant polycystic kidney disease who are most likely to benefit from early intervention with novel treatments.