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.     

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.     

Renal artery occlusion in autosomal dominant polycystic kidney disease

Several vascular abnormalities have been reported in autosomal dominant polycystic kidney disease (ADPKD). Occlusion of the renal artery is uncommon in ADPKD and can be associated with hypertension. We report a 38-year-old woman with ADPKD and severe hypertension, abdominal magnetic resonance angiogram and arteriography revealed left renal artery total occlusion. A revascularization approach was not considered feasible and she was given conservative treatment. We review the literature and make some comments about renal artery occlusion in ADPKD. This association should be kept in mind in cases of ADPKD with severe or resistant hypertension.     

Pathways of apoptosis in human autosomal recessive and autosomal dominant polycystic kidney diseases

Autosomal dominant polycystic kidney disease (ADPKD) is a major cause of end-stage renal disease in adults. Autosomal recessive (AR) PKD affects approximately 1:20,000 live-born children with high perinatal mortality. Both diseases have abnormalities in epithelial proliferation, secretion, and cell-matrix interactions, leading to progressive cystic expansion and associated interstitial fibrosis. Cell number in a kidney reflects the balance between proliferation and apoptosis. Apoptosis results from extrinsic (ligand-induced, expression of caspase-8) and intrinsic (mitochondrial damage, expression of caspase-9) triggers. Previous studies have suggested a role for apoptosis in PKD cyst formation and parenchymal destruction. Mechanisms underlying apoptosis in human ADPKD and ARPKD were examined by quantitative immunohistochemistry and Western immunoblot analyses of age-matched normal and PKD tissues. Caspase-8 expression was significantly greater in small cysts and normal-appearing tubules than in larger cysts in ADPKD kidneys. Caspase-8 also appeared early in the disease process of ADPKD. In ARPKD, expression of caspase-8 was most pronounced in later stages of the disease and was not confined to a specific cyst size. In conclusion, apoptosis in human ADPKD is an early event, occurring predominantly in normal-appearing tubules and small cysts, and is triggered by an extrinsic factor, but it occurs later in ARPKD.     

Intracranial aneurysms and dolichoectasia in autosomal dominant polycystic kidney disease.

BACKGROUND: Intracranial saccular aneurysms (ICA) are a known extrarenal manifestation of autosomal dominant polycystic kidney disease (ADPKD). In order to facilitate the definition of subgroups who are at risk for ICA and to determine the prevalence of ICA in these subgroups we studied ADPKD patients with a positive family history for a cerebral event, including cerebral stroke (group I) and intracranial bleeding or known ICA (group II). METHODS: Within an enrolment period of 21 months, 43 ADPKD patients from our outpatient clinic and hospital were examined with cerebral magnetic resonance angiography (MRA). RESULTS: ICA were detected in six patients (14%). Three out of 32 patients (9.4%) in group I and three out of 11 patients (27.3%) in group II had an ICA. A dolichoectasia of intracerebral vessels was found in two out of 43 patients (4.7%). CONCLUSIONS: Using MRA a high prevalence of ICA was shown only in patients with a family history of cerebral bleeding or ICA. A family history for cerebral stroke does not imply an elevated risk for ICA. However, dolichoectasia, rare in the normal population, was detected in two patients. We recommend screening for ICA in patients with a positive family history for cerebral bleeding or ICA. Because of potential complications, examiners should direct their attention to dolichoectasia in ADPKD patients.     

Pretransplant bilateral hand-assisted laparoscopic nephrectomy in adult patients with polycystic kidney disease.

Laparoscopic procedures continue to gain popularity over traditional open procedures for a number of abdominal and pelvic surgeries. With increasing experience, the application of this technique is rising because it provides an alternative, less invasive, approach to various surgical procedures. Herein, we report our experience with adult patients with polycystic kidney disease, requiring bilateral laparoscopic nephrectomy before renal transplantation.     

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,     

Cyst sclerotherapy with minocycline hydrochloride in patients with autosomal dominant polycystic kidney disease

BACKGROUND: The enlarged cysts in autosomal dominant polycystic kidney disease(ADPKD) frequently cause abdominal discomfort. Cyst sclerotherapywith minocycline hydrochloride was performed to relieve thissymptom. METHODS: Ten symptomatic ADPKD cases were recruited. As a sclerosant,minocycline hydrochloride solution (10 mg/dl) was used. Thissolution was instilled into the cysts under ultrasonographiccontrol. Renal volume was calculated before therapy and at 6-monthintervals thereafter. Renal function and blood pressure wereregularly monitored. The effect of sclerotherapy on symptomswas also assessed at 6-month intervals. RESULTS: At 6 months, renal volume was statistically lower than the presclerotherapy,and was associated with improvement in chronic symptoms. However,such ameliorating effects were blunted at 12 months. Renal volumereduction at 6 and 12 months showed a significant positive correlationwith the dose of minocycline injected. No significant influencein renal function and blood pressure was observed. CONCLUSIONS: These results suggest that cyst sclerotherapy with minocyclinehydrochloride is a valid treatment regime for the relief ofchronic symptoms in ADPKD cases, although repeated applicationof this approach may be required to obtain a more long-termeffect.     

Urinary tract infections,VUR, and autosomal dominant polycystic kidney disease

This case series of 16 patients with autosomal dominant polycystic kidney disease (ADPKD) describes 4 girls who presented with a urinary tract infection (UTI). Radiological evaluation revealed that each of these patients had vesicoureteral reflux (VUR). The frequency of VUR was significantly higher in the patients with ADPKD compared with otherwise healthy age-matched children who underwent testing after a UTI (100% versus 15%, P<0.002). These findings suggest VUR is an associated somatic anomaly in children with ADPKD that may contribute to the occurrence of UTI in this patient population.     

Selective, concurrent bilateral nephrectomies at renal transplantation for autosomal dominant polycystic kidney disease

PURPOSE: An algorithm was developed for performing bilateral nephrectomies for specific indications before or at renal transplantation in patients with autosomal dominant polycystic kidney disease. Outcomes for the living donor arm of the algorithm are reported. MATERIALS AND METHODS: Patients with autosomal dominant polycystic kidney disease and end stage renal disease were evaluated for transplantation. Patients with recurrent pyelonephritis, hemorrhage, pain, early satiety or kidneys that extended into the true pelvis underwent bilateral nephrectomies. Bilateral nephrectomies with concurrent renal transplantation were performed if a living renal donor was identified. If no living donor was identified, pre-transplantation bilateral nephrectomies were done and the patients were listed for cadaveric donor renal transplantation. The living renal donor arm of the algorithm was evaluated by comparing certain parameters for 15 and 17 patients with autosomal dominant polycystic kidney disease who underwent pre-transplantation and concurrent bilateral nephrectomies, respectively, including patient and graft survival, delayed graft function, graft function, length of stay for each surgery, transfusions and complications. RESULTS: No deaths, graft failures or delayed graft function occurred. In the delayed renal transplant group median time from nephrectomy to living donor transplantation was 124 days. Serum creatinine at discharge home and 1 year after transplantation for the pre-transplantation nephrectomy cohort was 2.0 and 1.3 mg/dl, respectively. Seven of the 17 patients with concurrent nephrectomy underwent transplantation before starting renal replacement therapy. A longer mean total hospital stay in the pre-transplantation nephrectomy cohort was the only statistically significance outcome variable. CONCLUSIONS: Selective bilateral nephrectomies at living donor renal transplantation results in decreased total length of stay without compromising patient or graft outcomes and it allows preemptive renal transplantation. Concurrent nephrectomy is safe and it further validates the algorithm for selective, concurrent bilateral nephrectomies for patients with autosomal dominant polycystic kidney disease who undergo living donor renal transplantation.     

End stage polycystic kidney disease: indications and timing of native nephrectomy relative to kidney transplantation

PURPOSE: We evaluated the indications for and outcome of pre-transplant, concomitant and post-transplant native nephrectomy in patients with end stage polycystic kidney disease (PCKD). MATERIALS AND METHODS: The records of 32 patients were retrospectively reviewed using the electronic database at our institution. RESULTS: Between January 1992 and December 2002, 171 patients with end stage PCKD received a kidney transplant at University of California-San Francisco. A total of 32 patients (18.7%) underwent pre-transplant (7, group 1), concomitant (16, group 2) or post-transplant (9, group 3) native nephrectomy. Of these patients 25 underwent bilateral nephrectomy. Median followup was 18 months. Indications for nephrectomy were hematuria, a renal mass and chronic pain in group 1, lack of space in group 2 and urinary tract infection in group 3. Mean operative time +/- SEM was 231 +/- 14, 370 +/- 24 and 208 +/- 14 minutes in groups 1 to 3, respectively (p = 0.001). Mean intraoperative blood loss was 533 +/- 105, 573 +/- 155 and 522 +/- 181 ml in groups 1 to 3, respectively (p not significant). Two group 2 patients required blood transfusions. Postoperative complications requiring surgical intervention included wound dehiscence in group 1 and abdominal bleeding in group 3. Mean hospital stay was comparable among groups 1 to 3 at 7 +/- 0.7, 8.6 +/- 1.2 and 6.3 +/- 0.6 days, respectively (p not significant). At 3 months mean serum creatinine was not significantly different between groups 2 and 3 at 1.3 +/- 0.1 and 1.5 +/- 0.2 mg/dl, respectively. CONCLUSIONS: Unilateral or bilateral nephrectomy for PCKD at transplantation is safe in terms of postoperative patient morbidity and graft function. We perform concomitant native nephrectomy when indicated, preferably in recipients of living donor kidney transplants.     

Laparoscopic renal denervation and nephropexy for autosomal dominant polycystic kidney disease related pain in adolescents

PURPOSE: We present our initial experience with laparoscopic renal denervation and nephropexy for ADPKD related pain in the adolescent population. MATERIALS AND METHODS: Four patients 15 to 19 years old previously diagnosed with ADPKD presented with chronic pain refractory to narcotic analgesics. These 4 patients underwent laparoscopic renal denervation of 5 kidneys. RESULTS: Mean operative time was 136 minutes and mean hospital stay was 2.75 days. All patients were pain-free at discharge home and remained pain-free at a mean followup of 11.5 months. CONCLUSIONS: We believe that laparoscopic renal denervation plus nephropexy is a promising option for uncontrolled ADPKD related pain in the adolescent population.     

Laparoscopic nephrectomy for autosomal dominant polycystic kidney disease

Background The authors reviewed their experience with laparoscopic nephrectomy for autosomal dominant polycystic kidney disease to evaluate whether patient-related or surgery-related factors influence operative outcomes.Methods A retrospective review was carried out of 22 consecutive laparoscopic nephrectomies performed by one surgeon in a university setting between March 1998 and March 2003. The impact of patient factors (body mass index, preoperative hemoglobin level, preoperative blood urea nitrogen and creatinine, kidney size and side, prior abdominal surgery, dialysis) and surgical factors (surgeon experience and preoperative embolization) on short-term outcomes (estimated blood loss, transfusion requirements, operative time, conversion, intra- and postoperative complications and length of stay) was analyzed using the Students t-test, Pearson correlation, and Mann–Whitney and Fisher tests.Results A total of 19 patients underwent 22 nephrectomies. The average patient age was 49 years (range, 36–65 years) and the average body mass index was 31.4 kg/m² (range, 20.4–64.5 kg/m²). Fourteen patients (68%) were receiving dialysis. Fifteen right (68%) and 7 left (32%) nephrectomies were performed. The median kidney size was 22 cm (range, 8–50 cm). Five patients (23%) had preoperative embolization. The median operative time was 255 min (range, 95–415 min). There were no mortalities. The intraoperative complication rate was 18% (1 vena cava laceration, 1 cecal perforation, 1 dialysis fistula thrombosis, 1 intrarenal bleeding requiring conversion), and the postoperative complication rate was 32% (1 myocardial infarction, 1 urgent laparotomy for clinical peritonitis, 1 minor bile fistula, 1 AV fistula thrombosis, 2 incisional hernias, 1 urinary retention). Four procedures (18%) were converted (1 for vena cava laceration, 1 for cecal perforation, 1 for intrarenal bleeding, 1 for adhesions). The median blood loss was 400 ml (range, 100–5000 ml). Eight patients (36%) received transfusions (median, 2 units). The median length of stay was 4 days. The patients who required blood transfusions had lower preoperative hemoglobin levels. Preoperative embolization did not affect surgical outcome. However, surgeon experience significantly reduced operative time.Conclusions Laparoscopic nephrectomy for autosomal dominant polycystic kidney disease is a safe procedure, providing patients with a short hospital stay. Complication and conversion rates are relatively high.Presented at the 11th International Congress of the European Association for Endoscopic Surgery and other Interventional Techniques (EAES), Glasgow, 15–18 June 2003     

Pretransplant laparoscopic nephrectomy in adult polycystic kidney disease: a single centre experience

OBJECTIVE

To report our experience with pretransplant laparoscopic nephrectomy in patients with autosomal dominant polycystic kidney disease (ADPKD), as ADPKD often progresses to end‐stage renal disease and most azotaemic patients with ADPKD have enlarged kidneys, making graft placement difficult.

MATERIAL AND METHODS

We retrospectively reviewed the medical records of 13 patients with renal failure attributable to ADPKD who underwent pretransplant laparoscopic nephrectomy (21 renal units) from August 2002 to December 2006. Five patients had a unilateral nephrectomy, seven had a staged bilateral nephrectomy, and one had a simultaneous bilateral nephrectomy. All patients underwent subsequent living‐related renal transplantation. The operative duration, haemoglobin decrease, blood transfusion, hospital stay, analgesic requirement and time to receipt of a transplant were compared with those of patients who underwent open pretransplant nephrectomy (14 patients) from 1984 to 2001.

RESULTS

Kidneys of a size to interfere with graft placement were the commonest indication for surgery (eight patients). In comparison with open surgery, the mean (sd ) hospital stay at 9.26 (2.9) vs 4.86 (0.9) days, analgesic requirement at 320 (120) vs 221 (120.5) mg of tramadol, blood transfusion rate at 1.3 (0.5) vs 0.9 (0.6) units, period to receive a graft kidney at 29.77 (4.6) vs 9.14 (3.38) days, were significantly less with laparoscopy. The complications noted were single instances of splenic capsular tear, pleural tear, sub‐acute intestinal obstruction and vena caval injury.

CONCLUSION

Pretransplant laparoscopic nephrectomy in patients with ADPKD has all the benefits of minimally invasive surgery such as reduced intraoperative blood loss and minimal postoperative pain leading to early and faster convalescence. These benefits help in decreasing the period between nephrectomy and transplantation. The surgeon needs to have considerable experience in laparoscopy before embarking on laparoscopic pretransplant nephrectomy.     

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。     

Retinitis pigmentosa associated with autosomal dominant polycystic kidney disease

SUMMARY: We report a case of a 35-year-old man with autosomal dominant polycystic kidney disease (ADPKD) who presented for the first time with end-stage renal failure. He had a long history of blurred vision and on examination had retinitis pigmentosa. to our knowledge, this is the second report on the association of retinitis pigmentosa with polycystic kidney disease.     

Retinitis pigmentosa associated with autosomal dominant polycystic kidney disease

We report a case of a 35-year-old man with autosomal dominant polycystic kidney disease (ADPKD) who presented for the first time with end-stage renal failure. He had a long history of blurred vision and on examination had retinitis pigmentosa. To our knowledge, this is the second report on the association of retinitis pigmentosa with polycystic kidney disease.