Autosomal Dominant Polycystic Kidney Disease Patient Research Articles

Fifteen-Year Follow-up of Transplantation of a Cadaveric Polycystic Kidney: A Case Report

Introduction Kidneys from donors affected by autosomal-dominant polycystic kidney disease (ADPKD) are in general considered unsuitable for transplantation. To the best of our knowledge, only 12 cases of ADPKD transplanted renal units have been reported in the English literature; most have only short-term follow-up. Methods We provide a review of these patients and share our experience with an ADPKD patient who received a 21-year-old deceased donor ADPKD-affected renal transplant and has been closely followed for 15 years. Based on the current literature, this report is the longest follow-up of a ADPKD donor transplant. Results Over the 15-year follow-up period, there have been no complications related to the ADPKD-affected donor kidney, including three kidney transplant biopsies. The graft continues to function well with the serum creatinine currently 1.2 mg/dL. Serial axial imaging has demonstrated that the cystic disease has slowly progressed in the donor renal unit, with the largest cyst having only increasing from 1.2 to 2.9 cm in diameter. Metachronous, bilateral laparoscopic nephrectomies of the native kidneys were performed owing to intractable pain from cystic enlargement. Conclusions Normal functioning deceased donor kidneys that show signs of early ADPKD should be considered acceptable for donation in select cases. These organs provide the recipient a safe, reasonable period of graft survival and have not been shown to cause adverse effects.

Autosomal Dominant Polycystic Kidney Disease Is Associated With an Increased Prevalence of Radiographic Bronchiectasis

Autosomal dominant polycystic kidney disease (ADPKD) is a common disease with several known extrarenal manifestations, although no known pulmonary features. The formation of renal cysts in ADPKD has been attributed to dysfunction of primary cilia and the primary cilia-related proteins polycystin-1 (in 85% of cases) and polycystin-2 in renal epithelial cells. The goals of this study were to characterize the normal expression of polycystin-1 in the motile cilia of airway epithelial cells and to evaluate lung structure in ADPKD patients. Airway epithelium from non-ADPKD patients was immunostained to localize polycystin-1 expression, and lung tissue from ADPKD patients was examined for pathologic changes. CT scans from ADPKD patients (n = 95) and a control group of non-ADPKD chronic kidney disease patients (n = 95) were retrospectively reviewed for the presence of bronchiectasis using defined criteria. Immunostaining revealed polycystin-1 expression in the motile cilia of non-ADPKD airway epithelial cells. Lung tissue from one of five available ADPKD patient autopsies revealed histologic changes of bronchiectasis. Review of CT scans revealed a threefold-increased prevalence of bronchiectasis in the ADPKD group compared to the control group (37% vs 13%, p = 0.002). ADPKD patients demonstrate an increased prevalence of radiographic bronchiectasis, a previously unrecognized manifestation of the disease. This association suggests that patients with primary cilia-associated diseases may be at risk for airway disease.

A Case Report of a Pyogenic Liver Abscess Caused by Fusobacterium Nucleatum in a Patient With Autosomal Dominant Polycystic Kidney Disease Undergoing Hemodialysis

Pyogenic liver abscess (PLA) is a process with significant morbidity and mortality and is a rare complication in an aisled way in patients with autosomal dominant polycystic kidney disease (ADPKD). In addition to hepatic cyst infection, intracystic hemorrhage is another complication seen in ADPKD patients; however, the liver parenchyma itself remains normal. A PLA located in normal liver tissue in these kinds of patients has not been previously reported. Fusobacterium nucleatum is an anaerobic bacterium with rare involvement other than in periodontal infections. A 58-year-old Caucasian male, who was on hemodialysis treatment from July 2004 due to end-stage renal disease secondary to ADPKD, was admitted with fever, rigor, chills, weakness, and abdominal pain of 10 days duration. During that time, ciprofloxacin 500 mg, twice daily, gentamycin 80 mg/48 h, and vancomycin 1 g/week, were prescribed, but treatment was interrupted by hospitalization. Physical examination on admission revealed that the patient had a fever of 39.8 degrees C, pallor, chills, right upper quadrant abdominal pain, and hepatosplenomegaly. Abdominal ultrasound revealed a 5.3 cm diameter collection with irregular configuration located in the caudate lobe. Abdominal computed tomography (CT) showed a large multiloculated hepatic collection. The PLA was managed with antibiotics (metronidazole) and continuous catheter drainage (8Fr drainage catheters [Abocath-T, Abbott, Sligo, Ireland]) into the abscess. Fluid culture was positive for F. nucleatum. Complete remission was obtained after 12 days without complications. We describe a PLA by F. nucleatum, in a very rare location in an ADPKD patient undergoing hemodialysis without complicated cysts, managed with antibiotics and percutaneous drainage with satisfactory resolution.

Transplantation rénale pour polykystose rénale autosomique dominante : spécificités de la préparation et du suivi des patients

Autosomal dominant polycystic kidney disease (ADPKD) which accounts for 15% of all renal transplantations emerges as the third cause of kidney transplantation in France. In addition to routine evaluation before transplantation, the ADPKD patient requires special assessment of three aspects: should potential kidney complications (recurrent upper tract infection or haemorrhage) or kidney size assessed by computed tomography require nephrectomy prior to transplantation? Is it advisable to detect intracranial aneurysm (ICA) in patients with a relative having experienced ruptured ICA? When transplantation from a living relative is considered, the existence of ADPKD in the donor should be formally ruled out by imaging or genetic studies. The risk of recurrence of ADPKD post-transplantation does not exist. Nevertheless other complications may occur. Thus, an increased incidence of colonic perforation has been reported. In addition, as compared to non-ADPKD patients, an increased risk for both skin cancer and new-onset post-transplant diabetes mellitus has been reported recently after kidney transplantation. Finally, because these patients suffer from an inherited syndrome, physicians should carefully consider the personal and familial history before and after transplantation in order to respond to fatalism in some cases, or to attenuate excessive enthusiasm in the others. Altogether, it apears that a specific approach is needed for ADPKD patients when considering renal transplantation.

New insights into ADPKD molecular pathways using combination of SAGE and microarray technologies

Autosomal dominant polycystic kidney disease (ADPKD) is caused by mutations in the PKD1 or PKD2 gene, but cellular mechanisms of cystogenesis remain unclear. In an attempt to display the array of cyst-specific molecules and to elucidate the disease pathway, we have performed comprehensive high-throughput expression analysis of normal and ADPKD epithelia in a two-step fashion. First, we generated expression profiles of normal and cystic epithelia derived from kidney and liver using serial analysis of gene expression (SAGE). We found 472 and 499 differentially expressed genes with fivefold difference in liver and kidney libraries, respectively. These genes encode growth factors, transcription factors, proteases, apoptotic factors, molecules involved in cell–extracellular matrix interactions, and ion channels. As a second step, we constructed a custom cDNA microarray using a subset of the differentially regulated genes identified by SAGE and interrogated ADPKD patient samples. Subsequently, a set of differentially expressed genes was refined to 26 up-regulated and 48 down-regulated genes with a p value of <0.01. This study may provide valuable insights into the pathophysiology of ADPKD and suggest potential therapeutic targets.

Transplantation of a cadaveric polycystic kidney in a patient with autosomal dominant polycystic kidney disease: long-term outcome

Introduction Kidneys from donors affected by autosomal dominant polycystic kidney disease (ADPKD) were considered unusable for transplantation. To the best of our knowledge, seven cases worldwide have now been described in the English literature since 1967 suggesting such donor organs may be acceptable under certain conditions. Most of these reports have only short-term follow-up. Methods We provide a review of these patients and share our experience with an ADPKD patient who had a cadaveric ADPKD transplant and has been closely followed for 10 years. Results During the 10-year period, the patient had three transplant biopsies without complication. This creatinine is currently 1.2 mg/dL. Serial computed tomography imaging indicated that the cystic disease slowly progressed during this time period. He eventually developed intractable pain in his native left kidney and underwent a laparoscopic nephrectomy. Conclusions Normal functioning cadaveric kidneys that show early signs of polycystic kidney disease should be considered acceptable for renal donation. These organs provide the recipient a safe, reasonable period of graft survival and have not been shown to cause adverse effects.

Acceptance of the 2003 Jean Hamburger Award

Acceptance of the 2003 Jean Hamburger Award

Coronary aneurysms in patients with autosomal dominant polycystic kidney disease.

Patients with autosomal dominant polycystic kidney disease (ADPKD) have an increased risk of intracranial aneurysms. Reports on arterial aneurysms in other locations have not been conclusive. The present study was initiated to investigate the prevalence of coronary aneurysms. Thirty ADPKD patients who had undergone coronary angiography on clinical indication were identified, 15 after renal transplantation. For each ADPKD patient, a control patient was identified with end-stage renal disease, investigated by coronary angiography, and matched for age, sex, and time relation to transplantation. All angiograms were retrieved and reevaluated with respect to aneurysms, defined as an increase in artery diameter by 50% or more, as well as to pathologic ectasias not fulfilling this criterion. Aneurysms were detected in four ADPKD patients and two control subjects. Five more ADPKD patients, but none of the control subjects, had minor ectasias. One ADPKD patient had a dissecting aortic aneurysm, and another died of aortic dissection during bypass surgery. This study adds to the evidence of an increased risk of extracranial aneurysms in ADPKD patients.

Cytokine profile in autosomal dominant polycystic kidney disease.

To elucidate the pathogenetic mechanism of renal parenchymal injury in autosomal dominant polycystic kidney disease (ADPKD) patients, typically characterized by renal cystic changes paralleled by interstitial inflammation and gradual fibrotic changes, the role of selected inflammatory mediators was evaluated in a group of ADPKD patients with normal glomerular filtration rate. The plasma concentrations of IL-6, IL-8, ICAM-1 and VCAM-1 (which may reflect systemic response to inflammation/infection) were increased in the ADPKD patient group. Coupled with decreased urinary excretion of the IL-1 receptor antagonist (which exerts an anti-inflammatory role), these results suggest that even in overt infection free status, the proinflammatory system is more activated and anti-inflammatory defence system weakened in ADPKD subjects. Our data support the current view that cytokines are candidate contributors to pathogenesis of ADPKD.