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.     

Sarcomatoid transitional cell carcinoma originating from a duplicated renal pelvis

A case of sarcomatoid transitional cell carcinoma of the renal pelvis is reported. It was distinguished from carcinosarcoma by immunohistochemical study. The tumor was difficult to distinguish from a renal parenchymal tumor in imaging studies because it originated from a duplicated renal pelvis.     

Complications of autosomal dominant polycystic kidney disease in 50 haemodialysed patients. A case-control study

BACKGROUND: The impact of renal and extrarenal manifestations of autosomaldominant polycystic kidney disease (ADPKD) during chronic haemodialysis(HD) has never been assessed in a paired case-control study. METHODS: Comparison of the course of 50 ADPKD patients with 50 matchedcontrol (C) patients who started chronic HD at the same time. RESULTS: Follow-up averaged 48 and 39 months in the ADPKD and C groupsrespectively. Actuarial survival was similar in both groups.Prevalence of renal pain (36 vs 2%, P=0.0001), haematuria (36vs 16%, P<0.03) and renal infection (16 vs 2%, P<0.04)was higher in the ADPKD than in the C group. Nephrectomy duringHD was performed in six ADPKD (in 4 cases in preparation fortransplantation) and in one control patient. Number of patientswith coronary and heart valve complications was similar in bothgroups. Stroke occurred in three patients from both groups.Only two ADPKD patients experienced a single episode of painrelated to liver cyst. Prevalence of severe infection was similarin the ADPKD group (36%) and the C group (28%). Number and durationof hospitalizations were similar in both groups. CONCLUSIONS: The overall outcome of ADPKD patients on maintenance HD is similarto that of HD patients with other primary renal diseases. Complicationsrelated to cystic kidneys are frequent but rarely severe. Extrarenalmanifestations of ADPKD have a limited clinical impact in thisshort-term study.     

Outcomes of renal transplantation in patients with autosomal dominant polycystic kidney disease: a nationwide longitudinal study

Renal transplantation in patients with autosomal dominant polycystic kidney disease (ADPKD) is a medical and surgical challenge. Detailed longitudinal epidemiological studies on large populations are lacking and it is mandatory to care better for these patients. The success of such a project requires the development of a validated epidemiological database. Herein, we present the results of the largest longitudinal study to date on renal transplant in patients with ADPKD. The 15‐year outcomes following renal transplantation of 534 ADPKD patients were compared with 4779 non‐ADPKD patients. This comprehensive, longitudinal, multicenter French study was performed using the validated database, DIVAT (Données Informatisées et VAlidées en Transplantaion). We demonstrate that renal transplantation in ADPKD is associated with better graft survival, more thromboembolic complications, more metabolic complications, and increased incidence of hypertension, whereas the prevalence of infections is not increased. This study provides important new insights that could lead to a better care for renal transplant patients with ADPKD.     

Screening for intracranial aneurysms in autosomal dominant polycystic kidney disease

SUMMARY:   Screening patients with autosomal dominant polycystic kidney disease (ADPKD) for asymptomatic intracranial aneurysms has been proposed as a method of reducing the morbidity and mortality associated with aneurysm rupture. However, recent studies have shown lower spontaneous rupture rates of small aneurysms and higher risks of significant complications with interventions than previously reported. Risk-benefit analysis has not demonstrated any benefit of screening ADPKD patients without a history of subarachnoid haemorrhage (SAH) for intracranial aneurysms, and has suggested that screening might cause harm.     

Renal oncocytoma with bilateral synchronous renal cell carcinoma in a patient undergoing long-term hemodialysis

Abstract:   We report a case of bilateral synchronous renal cell carcinoma and renal oncocytoma in a 56-year-old male who had been treated with hemodialysis for 32 years. Because anemia gradually worsened, computed tomography and magnetic resonance imaging were carried out and revealed bilateral renal tumors within acquired cystic disease of the kidney. Bilateral nephrectomy was carried out, and the patient was diagnosed with multiple renal cell carcinomas and a single renal oncocytoma. To our knowledge, this is the first reported case of renal oncocytoma with synchronous renal cell carcinoma in a patient undergoing long-term hemodialysis.     

Angiotensin-converting enzyme activity and the ACE Alu polymorphism in autosomal dominant polycystic kidney disease.

BACKGROUND: Previous studies concerning Alu I/D polymorphism in the ACE gene and ADPKD severity have used the Alu genotypes as a representative of the true biological variable, namely ACE activity. However, wide individual and ethnic differences in the proportion of variance in ACE activity explained by the I/D genotype may have confounded these studies. This investigation examines the association between ADPKD severity and ACE in terms of plasma enzyme activity and I/D genotypes in individuals from three different countries. METHODS: Blood samples were collected from 307 ADPKD patients (116 Australian, 124 Bulgarian and 67 Polish) for determination of ACE activity levels and I/D genotypes. Chronic renal failure (CRF) was present in 117 patients and end-stage renal failure (ESRF) in 68 patients. RESULTS: ACE activity was related to the I/D genotype, showing a dosage effect of the D allele (P=0.006). The proportion of variance due to the Alu polymorphism was 14%. No difference in ACE activity and I/D genotype distribution was found between patients with CRF versus normal renal function (P=0.494; P=0.576) or between those with ESRF versus those without ESRF (P=0.872; P=0.825). No effect of the I/D genotype on age at development and progression to renal failure (CRF; ESRF) was detected in the overall group, and in subgroups based on ethnic origin, linkage status and sex. CONCLUSION: ACE is not likely to play a role as a determinant of ADPKD phenotype severity.     

Chromophobe renal cell carcinoma and 'capsulomas' with acquired cystic disease of the kidney in a long-term hemodialysis patient

Abstract:   Patients receiving long-term hemodialysis tend to develop renal cell carcinoma (RCC). Among such cases, chromophobe RCC and so-called 'capsulomas' are rarely reported. Here, we report a case of a Japanese woman in her early 70s, who developed both renal lesions after 17 years of hemodialysis. The patient received radical nephrectomy for enlarging renal mass. Grossly, the resected kidney showed a dominant tumor and small-sized subcapsular nodules. Histologically, two types of neoplasm, chromophobe RCC and 'capsuloma', existed with acquired cystic disease of the kidney. Chromophobe RCC had eosinophilic cytoplasm with perinuclear halos, and some tumor cells showed oncocytic features. Hale's colloidal iron staining showed a weakly positive cytoplasmic reaction. Immunohistochemistry was diffusely positive for cytokeratin 7, but negative for vimentin in the tumor cells. 'Capsulomas' were multiple subcapsular nodules composed almost entirely of smooth muscle-like cells with immunoreactivity for melanosome-associated antigen detected by HMB-45.     

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,     

Intraductal papillary mucinous tumor of the pancreas associated with autosomal dominant polycystic kidney disease

A 43-year-old male with a history of autosomal dominant polycystic kidney disease (ADPKD) was admitted to our center with severe abdominal pain and was diagnosed with acute pancreatitis. CT showed multiple cysts in the liver and both kidneys along with ADPKD and a cystic mass, 4 cm in diameter, in the pancreatic head. The main pancreatic duct was dilated to 1 cm in diameter. The patient was diagnosed with acute pancreatitis due to intraductal papillary mucinous tumor (IPMT), and pancreatoduodenectomy was performed. Histologic examination revealed a multiloculated cystic tumor filled with mucin in the head of the pancreas. Microscopically, the tumor was diagnosed as adenocarcinoma and was found to have invaded the main pancreatic duct. Although, in addition to our case, only seven cases with association between ADPKD and malignant neoplasms have been reported, five of these cases had neoplasms arising from the pancreas. Therefore, we suggest that some genetic interactions may exist between ADPKD and pancreatic carcinogenesis.     

常染色体显性遗传多囊肾的多囊素表达

目的研究多囊素的细胞定位,了解正常肾脏与肾组织多囊素的表达及分布差别。方法应用多囊素合成肽单抗抗ｐｅｐＰＢＰ１和抗ｐｅｐＰＢＰ３以及融合蛋白抗体抗ｆｐＡＨ４,对３例正常肾组织和８例多囊肾组织的标本做免疫组织化学染色定位。结果正常肾组织的多囊素组织化学定位主要分布在远端小管和集合管,髓质部更明显,近端小管弱染或阴性,肾小球上皮细胞也可着染。８例多囊肾组织的染色细胞在２８％～６０％,大多数为５０％,囊肿上皮染色比正常肾组织强,囊肿上皮染色强弱不同,少数囊肿上皮染色阴性。结论正常肾组织和多囊肾组织均可表达多囊素,多囊素染色以远端小管和集合管为主,细胞染色有差异性;多囊肾的囊上皮染色存在异质性。     

Causes analysis of 652 hospital stays in patients with autosomal dominant polycystic kidney disease

Objective To analyze the causes of 652 hospitalizations in the patients with autosomal dominant polycystic kidney disease (ADPKD). Methods The medical records of all ADPKD inpatients in our hospital from January 1, 1990 to December 31, 2010 were collected. The differences of hospitalization causes in different age, gender and period were analyzed. Results (1)In 652 hospitalizations, the most common cause was lumbar pain (15.2%), followed by cystic bleeding (14.6%), aggravating renal failure (10.1%), dialysis-related problems (9.4%), renal transplant related issues (8.3%), renal replacement therapy for ESRD (8.0%), urinary tract infection (6.4%), end stage renal failure (5.8%), hypertension (4.1%), renal cyst volume enlargement (3.7%), finding polycystic kidney disease (2.1%), urinary lithiasis (1.8%) and others (10.4%). (2)Younger patients were admitted into hospital because of polycystic kidney bleeding and finding PKD. With the increase of patients age, hospitalization due to dialysis-related problems increased, while many middle-aged patients were hospitalized because of back pain. (3)Male patients were admitted into hospital for aggravating renal failure, ESRD, kidney transplantation-related problems and urinary lithiasis, while female patients mainly for lumbar pain, dialysis-related problems and urinary tract infection. (4)The proportion was significantly reduced with time of finding PKD, renal failure and polycystic kidney bleeding, the proportion of renal cysts increasing and aggravating renal failure increased, there was a significant increase in the proportion of patients with hypertension, while a significant decrease in the proportion of patients with uncontrolled hypertension, and the average SBP was also significantly reduced. Conclusions The highest rate of hospitalization of ADPKD patients is in 40 to 60 age group. Cause of admission varies with age and gender, and changes with the change of time. Over the past decade, the proportion of hospitalization due to renal cysts enlargement and renal failure aggravation increased significantly. The incidence of hypertension is higher than that in the first 10 years, but hypertension control rate increases compared with the previous. Prevention should focus on finding the suppression measures of renal cysts enlargement.     

PKD2 mutations in a Czech population with autosomal dominant polycystic kidney disease.

BACKGROUND: Autosomal dominant polycystic kidney disease (ADPKD) is genetically heterogeneous and caused by mutations in at least three different loci. Based on linkage analysis, mutations in the PKD2 gene are responsible for approximately 15% of the cases. PKD2-linked ADPKD is supposed to be a milder form of the disease, its mean age of end-stage renal failure (ESRF) approximately 20 years later than PKD1. METHODS: We screened all coding sequences of the PKD2 gene in 115 Czech patients. From dialysis centres in the Czech Republic and from the Department of Nephrology of the General Hospital in Prague, we selected 52 patients (29 males, 23 females), who reached ESRF after the age of 63, and 10 patients (three males, seven females) who were not on renal replacement therapy at that age. The age of 63 was used as the cut-off because it is between the recently published ages of onset of ESRF for PKD1 and PKD2. From PKD families we also selected 53 patients (26 males, 27 females) who could be linked to either the PKD1 or PKD2 genes by linkage analysis. An affected member from each family was analysed by heteroduplex analysis (HA) for all 15 coding regions. Samples exhibiting shifted bands on gels were sequenced. RESULTS: We detected 22 mutations (six new mutations)-14 mutations in 62 patients (23%) with mild clinical manifestations, eight in 53 families (15%) with possible linkage to both PKD genes. As the detection rate of HA is approximately 70-80%, we estimate the prevalence of PKD2 cases in the Czech ADPKD population to be 18-20%. We identified nonsense mutations in eight patients (36.5%), frameshifting mutations in 12 patients (54.5%) and missense mutations in two patients (9%). CONCLUSION: In this study in the Czech population we identified 22 mutations (six of which were new mutations). The prevalence of PKD2 cases was 18-20% and the mean age of ESRF was 68.3 years. An at-least weak hot spot in exon 1 of the PKD2 gene was found.     

Renal and cardiac effects of antihypertensive treatment with ramipril vs metoprolol in autosomal dominant polycystic kidney disease.

BACKGROUND: Hypertension is a common complication in autosomal dominant polycystic kidney disease (ADPKD). This prospective randomized double-blind study was performed to compare the renal and cardiac effects of the ACE inhibitor ramipril and the beta-blocker metoprolol as first line therapy in ADPKD patients with hypertension. METHODS: Forty-six hypertensive ADPKD patients were randomized to either ramipril (n = 23) or metoprolol (n = 23). Twenty-four hour (24-h) ambulatory blood pressure (BP), glomerular filtration rate (GFR) as calculated by the Cockcroft and Gault formula, urinary albumin excretion (albumin/creatinine ratio), and left ventricular mass index (LVMI) were established at baseline and at yearly intervals. The total follow-up was 3 years. Baseline characteristics were similar in both groups. RESULTS: Mean arterial pressure (MAP) decreased significantly in both the ramipril and the metoprolol group (-8 +/- 2 and -6 +/- 2 mmHg; both P < 0.01). There was a significant decline in renal function during follow-up which was similar in patients treated with ramipril or metoprolol (-2.5 +/- 0.7 vs -2.9 +/- 0.8 ml/min/year; P = NS). After the 3 years follow-up, no differences in GFR, LVMI and urinary albumin excretion were observed between the ramipril and the metoprolol group (80.7 +/- 10.7 vs 78.0 +/- 7.6 ml/min, 102.6 +/- 6.8 vs 100.3 +/- 5.4 g/m(2); and 42.6 +/- 12.3 vs 70.3 +/- 32.5 mg/g, respectively; all P = NS). A post-hoc analysis evaluating the effects of BP control, revealed that LVMI increased in patients with standard BP control while it remained stable in patients with rigorous BP control with a significant difference in LVMI between the groups after 3 years of follow-up (110.5 +/- 6.3 vs 90.9 +/- 4.7 g/m(2); P = 0.017). Also, by the end of the study albuminuria was lower in patients with rigorous vs standard BP control (23.5 +/- 6.7 vs 94.8 +/- 35.4 mg/g; P = 0.05). CONCLUSIONS: In our study population of hypertensive ADPKD patients, no differences in renal function, urinary albumin excretion and LVMI were detected between those treated with ramipril or metoprolol, respectively, during a 3 years follow-up. Rigorous BP control prevented an increase in LVMI and reduced urinary albumin excretion, suggesting a crucial role of BP control for slowing progression of cardiac and renal organ damage in ADPKD.     

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.     

Chromophobe cell renal carcinoma with acquired cystic disease of the kidney in a long-term hemodialysis patient

We report a rare case of chromophobe cell renal carcinoma found in a 52-year-old female who had received hemodialysis therapy for 13 years. She was diagnosed as having a left renal tumor 7.5 cm in diameter with acquired cystic disease of the kidney (ACDK) by ultrasonographic examination during periodical systemic screening. As abdominal computed tomography scanning and enhanced color Doppler ultrasonography suspected that the hypervascular tumor was renal cell carcinoma, she underwent translumbar nephrectomy in July 2000. The histopathological diagnosis was chromophobe cell carcinoma with pT2 and grade 2 malignancy. Chromophobe cell carcinoma is uncommon among renal tumors with ACDK found in long-term hemodialysis patients.