Blood pressure and renal function in autosomal dominant polycystic kidney disease

  The purpose of this study was to identify hypertension in children and adolescents in an early stage of autosomal dominant polycystic kidney disease (ADPKD) by the application of ambulatory blood pressure monitoring (ABPM) over 24 h; 32 children and adolescents (mean age 12.3±4.7 years) were examined. The diagnosis was based on family history and ultrasound examination. In 21 children ADPKD was confirmed by molecular genetic analysis. At the time of the study, 45% patients were asymptomatic and all had glomerular filtration rates (GFRs) ≥65 ml/min per 1.73 m². By ABPM, 11 patients (34%) were defined as hypertensive (systolic or diastolic blood pressure >95th percentile), including 4 with an exclusive nocturnal hypertension. Of 7 patients with daytime hypertension, 4 had normal blood pressure by casual measurements. The nocturnal dip in blood pressure was reduced in 2 patients. Blood pressure correlated with renal size, but not with GFR, concentrating capacity, proteinuria, and plasma renin activity. The study reveals an early trend for increased blood pressure in children with ADPKD, requiring close supervision. Received October 18, 1996; received in revised form and accepted March 11, 1997     

Genotype-renal function correlation in type 2 autosomal dominant polycystic kidney disease

Autosomal dominant polycystic kidney disease (ADPKD) is a common Mendelian disorder that affects approximately 1 in 1000 live births. Mutations of two genes, PKD1 and PKD2, account for the disease in approximately 80 to 85% and 10 to 15% of the cases, respectively. Significant interfamilial and intrafamilial renal disease variability in ADPKD has been well documented. Locus heterogeneity is a major determinant for interfamilial disease variability (i.e., patients from PKD1-linked families have a significantly earlier onset of ESRD compared with patients from PKD2-linked families). More recently, two studies have suggested that allelic heterogeneity might influence renal disease severity. The current study examined the genotype-renal function correlation in 461 affected individuals from 71 ADPKD families with known PKD2 mutations. Fifty different mutations were identified in these families, spanning between exon 1 and 14 of PKD2. Most (94%) of these mutations were predicted to be inactivating. The renal outcomes of these patients, including the age of onset of end-stage renal disease (ESRD) and chronic renal failure (CRF; defined as creatinine clearance < or = 50 ml/min, calculated using the Cockroft and Gault formula), were analyzed. Of all the affected individuals clinically assessed, 117 (25.4%) had ESRD, 47 (10.2%) died without ESRD, 65 (14.0%) had CRF, and 232 (50.3%) had neither CRF nor ESRD at the last follow-up. Female patients, compared with male patients, had a later mean age of onset of ESRD (76.0 [95% CI, 73.8 to 78.1] versus 68.1 [95% CI, 66.0 to 70.2] yr) and CRF (72.5 [95% CI, 70.1 to 74.9] versus 63.7 [95% CI, 61.4 to 66.0] yr). Linear regression and renal survival analyses revealed that the location of PKD2 mutations did not influence the age of onset of ESRD. However, patients with splice site mutations appeared to have milder renal disease compared with patients with other mutation types (P < 0.04 by log rank test; adjusted for the gender effect). Considerable renal disease variability was also found among affected individuals with the same PKD2 mutations. This variability can confound the determination of allelic effects and supports the notion that additional genetic and/or environmental factors may modulate the renal disease severity in ADPKD.     

肾细胞凋亡与常染色体显性遗传性多囊肾病肾组织缺失的相关研究

目的 研究肾细胞凋亡与常染色体显性遗传性多囊肾病（ADPKD）肾组织进行性缺失的关系。方法 采用琼脂糖凝胶电泳、电镜和原位末端标记（TUNEL）法、Hoechst 33342染色法测定正常肾组织、ADPKD肾组织和体外培养的ADPKD囊肿衬里上皮细胞中凋亡DNA片段。对Tunel法结果作定量分析,计算机图象分析ADPKD肾脏CT检查中残余肾组织/囊肿组织截而积比值,与肾功能衰竭程度作相关分析。结果 无或有肾功能衰竭的ADPKD肾组织中肾小球、肾小管上皮和囊肿衬里上皮细胞、体外培养的ADPKD囊肿衬里上皮细胞均发生凋亡。正常肾组织中无细胞凋亡。ADPKD肾组织中平均每10个高倍视野凋亡的肾细胞计数,肾功能正常组（A组,3.60±1.22）与氮质血症期组（B组,8.17±1.56）、终末期肾衰组（C组,17.81±3.15）间比较差异有非常显著性意义（P<0.01）。ADPKD肾组织中凋亡肾细胞数与肾功能衰竭程度显著相关（r=0.95,P<0.01）。ADPKD残余肾组织/囊肿组织截面积比值,A组（2.04±0.32）与B组（0.91±0.03）、C组（0.37±0.09）间比较差异有非常显著性意义（P<0.01）。ADPKD肾功能分期相同组中凋亡肾细胞数与残余肾组织/囊肿组织截面积比值呈负相关（r=-0.90,P<0.05）。ADPKD残余肾组织/囊肿组织截面积比值与肾功能衰竭程度呈负相关（r=-0.80,     

The relationship between renal volume and renal function in autosomal dominant polycystic kidney disease

Background  

In patients with autosomal dominant polycystic kidney disease (ADPKD), renal cysts grow exponentially. Since remaining renal parenchyma has a capacity to compensate for the loss of glomerular filtration, the glomerular filtration rate (GFR) may be sustained until the disease progresses. The purpose of this study was to determine if renal volumetric indices and clinical parameters are associated with renal function in Japanese patients with ADPKD.     

Effect of simvastatin on renal function in autosomal dominant polycystic kidney disease.

BACKGROUND: In animal models, HMG-CoA reductase inhibitors were able to improve renal function and endothelium-dependent vascular reactivity. In various experimental renal diseases, including autosomal dominant polycystic kidney disease (ADPKD), HMG-CoA reductase inhibitors improved the rate of decline in renal function. We studied the effect of simvastatin on ADPKD patients. METHODS: In a double-blind cross-over study, 10 normocholesterolaemic ADPKD patients were treated in random order for 4 weeks with 40 mg simvastatin or placebo daily. After each treatment period, we investigated the effect of simvastatin on renal blood flow and endothelium-dependent vascular reactivity. These periods were separated by a 4-week wash-out period. RESULTS: After treatment with simvastatin, glomerular filtration rate (GFR) significantly increased from 124+/-4 ml/min to 132+/-6 ml/min (P<0.05). Simultaneously, effective renal plasma flow (ERPF) increased significantly from 494+/-30 ml/min to 619+/-67 ml/min after simvastatin treatment (P<0.05). These renal effects were accompanied by a significantly enhanced vasodilator response to acetylcholine in the forearm after simvastatin treatment. Total serum cholesterol levels were significantly reduced after treatment with simvastatin, from 4.24+/-0.32 to 3.17+/-0.22 mmol/l (P<0.001). CONCLUSION: We concluded that simvastatin treatment can ameliorate renal function in ADPKD patients, by increasing renal plasma flow, possibly via improvement of endothelial function. Long-term clinical trials with HMG-CoA reductase inhibitors are needed to confirm these results and to establish a chronic inhibiting effect of HMG-CoA reductase inhibitors on the progression towards end-stage renal disease in ADPKD patients.     

Assessment of renal function with color Doppler ultrasound in autosomal dominant polycystic kidney disease

BACKGROUND: Measurement of renal blood flow by color Doppler ultrasound is useful for assessment of renal function in a variety of renal disorders. In autosomal dominant polycystic kidney disease (ADPKD), however, it might be difficult to visualize interlobar arteries because of deformity of renal structure. To evaluate the usefulness of color Doppler in ADPKD, parameters determined by blood flow examination were compared with the results of ordinal renal function tests. METHODS: Twenty-one patients with ADPKD were examined by color Doppler ultrasound measurement. In each patient, 10 interlobar arteries in both kidneys were investigated. Minimum blood flow velocity (Vmin), maximum blood flow velocity (Vmax), mean blood flow velocity (Vmean), acceleration, resistive index and pulsatility index were measured in relation to the results of creatinine clearance, serum creatinine, blood urea nitrogen and 15 and 120 min values of the phenolsulfonphthalein test. RESULTS: In all patients, interlobar arteries were able to be visualized and blood-flow profile was measured. Although variations of Vmin, Vmax, Vmean and acceleration were relatively large, the resistive index and pulsatility index varied little in each kidney. Mean values of Vmin (P < 0.005), Vmean (P < 0.05), resistive index (P < 0.005) and pulsatility index (P < 0.005) were well correlated to creatinine clearance with statistical significance. CONCLUSIONS: In ADPKD, color Doppler ultrasound measurement is a useful method for assessment of renal function and could be used for monitoring the dynamic state of renal blood flow as a non-invasive technique.     

常染色体显性多囊肾病肾功能与部分参数的相关性分析

目的采用彩色多普勒超声测定常染色体显性多囊肾病(ADPKD)患者肾脏体积、肾血管最大峰值流速(Vmax)、最小峰值流速(Vmin)、血流量及阻力指数(RI),观察患者肾脏体积及肾血流各参数的变化情况与肾功能变化的关系.方法选取ADPKD患者70例,应用彩色多普勒超声测定患者双肾大小,按公式计算肾脏体积;测量肾动脉及囊肿周边叶间动脉最大峰值流速(Vmax)、最小峰值流速(Vmin)及血流量,并计算RI.测定患者Scr、BUN及血Alb,根据MDRD公式计算肾小球滤过率(GFR).随访18个月后再行一次上述超声及肾功能检查,比较患者肾脏体积、血流量、肾血管RI及肾功能变化情况,作超声检查各参数变化绝对值与GFR变化绝对值的相关性分析.结果(1)GFR正常组随访前后肾功能、肾脏体积及肾血流各参数无显著差异.而GFR异常组在随访前较之GFR正常组,GFR显著降低,肾脏体积显著增大,肾血流量显著减少,RI显著升高;随访18个月后,GFR异常组患者较之随访前肾功能显著下降,肾脏体积显著增大,肾血流量显著减少,RI显著升高.(2)肾脏体积变化的绝对值与GFR变化的绝对值存在显著正相关;肾动脉及叶间动脉血流量变化及RI变化绝对值与GFR变化的绝对值存在显著正相关.结论定期采用彩色多普勒超声检测ADPKD患者的肾脏体积大小、肾血管血流量与RI,是临床监测疾病进展、确定治疗时机、评价治疗效果及预测疾病转归的一种敏感而简便的新手段.     

Long-term outcome of renal transplantation in autosomal dominant polycystic kidney disease

This study was performed to determine the long-term outcome of renal transplantation in 54 patients with end-stage renal failure secondary to autosomal dominant polycystic kidney disease (ADPKD) and in 107 patients with renal diseases other than ADPKD or diabetes mellitus matched by gender, age, year of transplantation, and source of the allograft. The overall patient survival and patient survival with a functioning first renal allograft were similar in both groups. Infection and cardiovascular accidents were the leading causes of early and late death in both groups. No cause of death was greatly overrepresented in the ADPKD group. Serious complications from extrarenal manifestations of ADPKD following renal transplantation included a ruptured intracranial aneurysm in one patient, a dissection of the ascending thoracic aorta in one patient, and infected hepatic cysts in two patients. Neoplasia (other than skin or cervical) occurred in four ADPKD patients and in one control patient and included one lymphoma in each group. Two ADPKD and one control patient had monoclonal gammopathies of undetermined significance. No complications related to the retention of native kidneys were detected in 12 ADPKD patients with a mean follow-up of 3 years. Cysts were observed in the renal allografts of some patients in both groups at autopsy and in a prospective computed tomography (CT) study of the allograft. However, we failed to detect a significant difference in the occurrence and number of the cysts between ADPKD and control patients.     

Hypertension in autosomal dominant polycystic kidney disease

Autosomal dominant polycystic kidney disease (ADPKD) has been shown to be associated with a greater than 50 percent incidence of hypertension prior to deterioration in renal function as assessed by glomerular filtration rate. The present study provides evidence for increased cardiac pre-load, as assessed by plasma atrial natriuretic factor (ANF) and cardiac index, in hypertensive as compared to normotensive ADPKD. The hypertensive ADPKD patients exhibited an increased renal vascular resistance as compared to the normotensive patients in spite of comparable glomerular filtration rates. It is hypothesized that the renal involvement of hypertensive ADPKD patients causes an impaired renal response to the observed increase in cardiac index, and also may release a venoconstrictor (such as angiotensin) which contributes to the enhanced cardiac pre-load and thus the hypertension.     

Evaluation of autosomal dominant polycystic kidney disease by DTPA renal scintigraphy

Sixty patients with previously documented autosomal dominant polycystic kidney disease (ADPKD) were investigated using dynamic kidney scintigraphy with^99mTc-diethylenetriaminepentaacetic acid (DTPA). Patients were subdivided in respect of glomerular filtration rate (GFR) as follows: PKD I group (normal GFR), PKD II group (moderately reduced GFR), and PKD III (severely reduced GFR). Seintigraphic features, time activity curves, excretion parameters, global and individual kidney functions were analyzed. Because of GFR dependent sensitivity, in advanced renal failure being only 0.1, and low reproducibility (11% intraobserver, 22% interobserver),^99mTc-DTPA dynamic kidney scintigraphy cannot be generally recommended for the diagnosis of ADPKD, but has to become a routine method for functional evaluation of both global and individual renal functions, as well as degree of excretion disturbances in ADPKD patients.     

Angiogenesis and autosomal dominant polycystic kidney disease

Autosomal dominant polycystic kidney disease (ADPKD) is characterized by the growth of multiple cysts that in many cases result in end-stage renal disease. Current strategies to reduce cyst progression in ADPKD focus on modulating cell turnover, fluid secretion, and vasopressin signalling; but an alternative approach may be to target pathways providing “general support” for cyst growth, such as surrounding blood vessels. This could be achieved by altering the expression of growth factors involved in vascular network formation, such as the vascular endothelial growth factor (VEGF) and angiopoietin families. We highlight the evidence that blood vessels and vascular growth factors play a role in ADPKD progression. Recent experiments manipulating VEGF in ADPKD are described, and we discuss how alternative strategies to manipulate angiogenesis may be used in the future as a novel treatment for ADPKD.     

Nephrotic syndrome and rapid renal failure in autosomal dominant polycystic kidney disease

A 44-year-old man, with autosomal dominant polycystic kidney disease and hypertension under satisfactory control, developed nephrotic syndrome with negative serology. Open renal biopsy revealed focal glomerular sclerosis. Prior to the appearance of heavy proteinuria, serum creatinine was 1.7 mg/dl. After the nephrotic syndrome had been established, renal function deteriorated rapidly and hemodialysis was started within 2.6 years. In patients with autosomal dominant polycystic kidney disease, the appearance of nephrotic range proteinuria along with a rapid decline in renal function indicates the presence of a glomerular lesion, which needs to be investigated by renal biopsy.     

Renal disease progression in autosomal dominant polycystic kidney disease

Background

Autosomal dominant polycystic kidney disease is a lifelong progressive disorder. However, how age, blood pressure, and stage of chronic kidney disease (CKD) affect the rate of kidney function deterioration is not clearly understood.

Methods

In this long-term observational case study up to 13.9?years (median observation period for slope was 3.3?years), serum creatinine was serially measured in 255 mostly adult patients. The glomerular filtration rate was estimated (eGFR) using a modified Modification of Diet in Renal Disease Study method. The total kidney volume (TKV) has been measured in 86 patients at one center since 2006.

Results

As age increased, eGFR declined significantly (P?Conclusion The declining rate of eGFR was relatively constant and did not correlate with age or eGFR after adolescence. eGFR was already low in young adult patients with hypertension. As age increased after adolescence, eGFR declined and TKV increased similarly between normal and high blood pressure groups. eGFR starts to decline in patients with normal eGFR, suggesting that the decline starts earlier than previously thought.     

Mineral bone disease in autosomal dominant polycystic kidney disease

1. Download : Download high-res image (287KB)
2. Download : Download full-size image

     

Renal infections in autosomal dominant polycystic kidney disease

Renal infection is a common occurrence in autosomal dominant polycystic kidney disease (ADPKD) and often leads to serious complications, including perinephric abscess, septicemia, and death. Important predisposing factors include age, female sex, and recent instrumentation of the urinary tract. Renal infections in ADPKD are most commonly caused by gram-negative enteric organisms. Diagnosis of these infections may be difficult since some patients do not have bacteriuria. Eradication of cyst infections with conventional antibiotic therapy can be difficult despite in vitro sensitivity of responsible organisms to the agents administered. We review recent studies of the anatomic and functional characteristics of renal cysts and discuss their possible relevance to the treatment of renal cyst infections. Finally, we set forth guidelines for the use of diagnostic studies, antimicrobial therapy, and surgical intervention for polycystic kidney infections.     

Urinary citrate as a marker of renal function in patients with autosomal dominant polycystic kidney disease

International Urology and Nephrology - Autosomal dominant polycystic kidney disease (ADPKD) is frequent to find low urinary citrate levels. Recently, it has been suggested that urinary citrate...