MR Brain Screening in ADPKD Patients

Background Adult polycystic kidney disease (ADPKD) still represents a major cause of renal failure and intracranial aneurisms (IA) have a higher prevalence in ADPKD than in the general population. Current guidelines suggest performing brain MRI only in the subjects with a positive familiar history of IAs or subarachnoid hemorrhage (SAH). This is a retrospective case-control analysis to evaluate the usefulness of a MR screening program in ADPKD patients. Methods We retrospectively analyzed all ADPKD patients followed in our outpatient clinic between 2016 and 2019 who underwent a brain MRI screening. We evaluated the presence of IAs and others brain abnormalities and compared our results with a non-ADPKD population (n = 300). We performed univariate and multivariate regression analysis to evaluate if general and demographic features, laboratory findings, clinical parameters and genetic test results correlated with IAs or other brain abnormalities presence. Results Among the patients evaluated 17 out of 156 (13.6%) ADPKD patients had IAs, compared to 16 out of 300 (5.3%) non-ADPKD controls (p < 0.005). Considering ADPKD patients presenting IAs, 12 (70.6%) had no family history for IAs or SAH. Genetic analysis was available for 97 patients: in the sub-population with IAs, 13 (76.5%) presented a PKD1 mutation and none a PKD2 mutation. We found that arachnoid cysts (AC) (p < 0.001) and arterial anatomical variants (p < 0.04) were significantly more frequent in ADPKD patients. Conclusion In our population ADPKD patients showed a higher prevalence of IAs, AC and arterial variants compared to non-ADPKD. Most of the IAs were found in patients presenting a PKD1 mutation. We found a significant number of alterations even in those patients without a family history of IAs or SAH. The practice of submitting only patients with familial IAs or kidney transplantation candidates to MRI scan should be re-evaluated.

Renal Transplantation from a Deceased Donor with Polycystic Kidney Disease

Renal transplantation is the gold standard treatment for patients with end-stage renal disease (ESRD) as it demonstrates improved long-term survival compared to patients who remain on renal replacement therapy. The widening gap between the demand and supply of organs warrants the expansion of donor criteria for renal transplantation. Kidneys with multiple cysts are often rejected for transplantation. Here, we present our recent experience of a 72-year-old patient with ESRD due to a biopsy-proven diabetic nephropathy who received a deceased donor kidney with adult polycystic kidney disease (APKD). At 31-month posttransplant, he had a serum creatinine of 1.6 mg/dL. Deceased donors affected by APKD should be considered an acceptable option for successful renal transplantation in select recipients, as well as an alternative kidney source to increase the donor pool.

Functional megalin is expressed in renal cysts in a mouse model of adult polycystic kidney disease

Background Autosomal dominant polycystic kidney disease (ADPKD) is characterized by the progressive growth of cysts and decline of renal function. The clinical feasibility of a number of potential disease-modifying drugs is limited by systemic, adverse effects. We hypothesize that megalin, a multi-ligand endocytic receptor expressed in the proximal tubule, may be used to facilitate drug uptake into cysts, thereby allowing for greater efficacy and fewer side effects. Methods The cyst expression of various tubular markers including megalin and aquaporin 2 (AQP2) was analyzed by immunohistochemistry (IHC) of kidney sections from the ADPKD mouse model (PKD1RC/RC) at different postnatal ages. The endocytic function of megalin in cysts was examined by IHC of kidney tissue from mice injected with the megalin ligand aprotinin. Results Cyst lining epithelial cells expressing megalin were observed at all ages; however, the proportion decreased with age. Concomitantly, an increasing proportion of cysts revealed a partial expression of megalin, expression of AQP2 or no expression of examined markers. Endocytic uptake of aprotinin was evident in megalin positive cysts, but only in those that remained connected to the renal tubular system. Conclusions Megalin expressing cysts were observed at all ages, but the proportion decreased with age possibly due to a switch in tubular origin, a merging of cysts of different tubular origin and/or a change in the expression pattern of cyst lining cells. Megalin expressed in cysts was functional suggesting that megalin-mediated endocytosis is a potential mechanism for drug targeting in ADPKD if initiated early in the disease.

Primary Histiocytic Sarcoma in Adult Polycystic Kidney Disease: Case Report and Review of Literature

Genetically driven tissue destruction followed by remodeling in adult polycystic kidney disease (APKD) raises the possibility of malignant transformation. Renal cell carcinoma (RCC) associated with APKD has been frequently reported in the literature; however, only a few cases of nonepithelial neoplasms arising in APKD have been described so far. Histiocytic sarcoma (HS) is a lymphohematopoietic malignant neoplasm that accounts for less than 1% of hematologic malignancies. In this article, we describe a case of primary HS occurring in a 61-year-old man with end-stage renal disease secondary to APKD. This is the first reported case of primary HS in the setting of APKD. The aberrant h-caldesmon expression seen in this case is another novel finding that has previously not been described. This case highlights the importance of morphology in guiding diagnostic workup and reiterates the necessity of maintaining a high index of suspicion for neoplastic entities in APKD.