Management of autosomal dominant polycystic kidney disease in the era of disease-modifying treatment options

Autosomal dominant polycystic kidney disease (ADPKD) is the reported etiology in 10% of end-stage kidney disease (ESKD) patients and has an estimated prevalence of 12.5 million cases worldwide across all ethnicities. There have been major advancements over the last two decades in understanding the pathogenesis and development of disease-modifying treatment options for ADPKD, culminating in regulatory approval of tolvaptan for ADPKD patients at risk of rapid progression to kidney failure. This review highlights the genetic mutations associated with ADPKD, defines patients at risk of rapid progression to ESKD, and focuses on the management of ADPKD in the era of disease-modifying agents

A practical guide for the management of acute abdominal pain with fever in patients with autosomal dominant polycystic kidney disease.

peer reviewedAutosomal dominant polycystic kidney disease (ADPKD) is characterized by the development of numerous renal cysts leading to kidney enlargement and chronic kidney disease. Extra-renal manifestations, including polycystic liver disease and connective tissue defects, are frequently observed in ADPKD. Acute cyst complications, i.e. hemorrhage and infection, represent rare but severe conditions of ADPKD. The distinction between cystic versus non-cystic abdominal complications is often problematic. Here, we propose a practical guide for the diagnostic and therapeutic management of an "acute abdominal pain with fever" in patients with ADPKD

Outcomes of patients with autosomal‐dominant polycystic kidney disease on peritoneal dialysis: A meta‐analysis

Background: Complications related to peritoneal dialysis (PD) in patients with autosomal-dominant polycystic kidney disease (ADPKD), including intraperitoneal rupture of renal cyst, hernia, membrane failure and peritonitis, have been reported. However, long-term clinical outcomes of ADPKD patients on PD remain unclear. We performed this meta-analysis to assess the risks of death, technique failure and peritonitis in ADPKD patients on PD. Methods: A systematic review was conducted using MEDLINE, EMBASE and Cochrane databases from inception to October 2017 to identify studies that evaluated the outcomes of ADPKD patients on PD, including the risks of death, technique failure and peritonitis. Non-ADPKD patients on PD were used as controls. Effect estimates from the individual study were extracted and combined using the random-effect, generic inverse variance method of DerSimonian and Laird. Results: Twelve cohort studies with a total of 14 673 patients on PD (931 ADPKD and 13 742 non-ADPKD patients) were enrolled. Compared with non-ADPKD status, ADPKD was associated with significantly decreased mortality risk with pooled odds ratio (OR) of 0.68 (95% confidence interval (CI), 0.53–0.86; I 2 = 0). There were no associations of ADPKD with the risks of technique failure of PD and peritonitis with pooled OR of 0.93 (95% CI, 0.79–1.10; I 2 = 0) and 0.88 (95% CI, 0.75–1.05; I 2 = 0), respectively. We found no publication bias as assessed by Egger\u27s regression asymmetry test, with P = 0.90, 0.28 and 0.60 for the risks of mortality, technique failure and peritonitis in ADPKD patients on PD, respectively. Conclusion: Compared with non-ADPKD patients on PD, our study demonstrates that ADPKD patients on PD have 0.68-fold decreased mortality risk. There are no associations of ADPKD status with the risks of technique failure or peritonitis

Outcomes of Patients With Autosomal-Dominant Polycystic Kidney Disease on Peritoneal Dialysis: A Meta-Analysis

Background: Complications related to peritoneal dialysis (PD) in patients with autosomal-dominant polycystic kidney disease (ADPKD), including intraperitoneal rupture of renal cyst, hernia, membrane failure and peritonitis, have been reported. However, long-term clinical outcomes of ADPKD patients on PD remain unclear. We performed this meta-analysis to assess the risks of death, technique failure and peritonitis in ADPKD patients on PD. Methods: A systematic review was conducted using MEDLINE, EMBASE and Cochrane databases from inception to October 2017 to identify studies that evaluated the outcomes of ADPKD patients on PD, including the risks of death, technique failure and peritonitis. Non-ADPKD patients on PD were used as controls. Effect estimates from the individual study were extracted and combined using the random-effect, generic inverse variance method of DerSimonian and Laird. Results: Twelve cohort studies with a total of 14 673 patients on PD (931 ADPKD and 13 742 non-ADPKD patients) were enrolled. Compared with non-ADPKD status, ADPKD was associated with significantly decreased mortality risk with pooled odds ratio (OR) of 0.68 (95% confidence interval (CI), 0.53–0.86; I 2 = 0). There were no associations of ADPKD with the risks of technique failure of PD and peritonitis with pooled OR of 0.93 (95% CI, 0.79–1.10; I 2 = 0) and 0.88 (95% CI, 0.75–1.05; I 2 = 0), respectively. We found no publication bias as assessed by Egger\u27s regression asymmetry test, with P = 0.90, 0.28 and 0.60 for the risks of mortality, technique failure and peritonitis in ADPKD patients on PD, respectively. Conclusion: Compared with non-ADPKD patients on PD, our study demonstrates that ADPKD patients on PD have 0.68-fold decreased mortality risk. There are no associations of ADPKD status with the risks of technique failure or peritonitis

Subarachnoid Hemorrhage in Hospitalized Renal Transplant Recipients with Autosomal Dominant Polycystic Kidney Disease: A Nationwide Analysis

Background: This study aimed to evaluate the hospitalization rates for subarachnoid hemorrhage (SAH) among renal transplant patients with adult polycystic kidney disease (ADPKD) and its outcomes, when compared to non-ADPKD renal transplant patients. Methods: The 2005–2014 National Inpatient Sample databases were used to identify all hospitalized renal transplant patients. The inpatient prevalence of SAH as a discharge diagnosis between ADPKD and non-ADPKD renal transplant patients was compared. Among SAH patients, the in-hospital mortality, use of aneurysm clipping, hospital length of stay, total hospitalization cost and charges between ADPKD and non-ADPKD patients were compared, adjusting for potential confounders. Results: The inpatient prevalence of SAH in ADPKD was 3.8/1000 admissions, compared to 0.9/1000 admissions in non-ADPKD patients (p < 0.01). Of 833 renal transplant patients with a diagnosis of SAH, 30 had ADPKD. Five (17%) ADPKD renal patients with SAH died in hospitals compared to 188 (23.4%) non-ADPKD renal patients (p = 0.70). In adjusted analysis, there was no statistically significant difference in mortality, use of aneurysm clipping, hospital length of stay, or total hospitalization costs and charges between ADPKD and non-ADPKD patients with SAH. Conclusion: Renal transplant patients with ADPKD had a 4-fold higher inpatient prevalence of SAH than those without ADPKD. Further studies are needed to compare the incidence of overall admissions in ADPKD and non-ADPKD patients. When renal transplant patients developed SAH, inpatient mortality rates were high regardless of ADPKD status. The outcomes, as well as resource utilization, were comparable between the two groups

Autosomal Dominant Polycystic Kidney Patients May Be Predisposed to Various Cardiomyopathies

Mutations in PKD1 and PKD2 cause autosomal dominant polycystic kidney disease (ADPKD). Experimental evidence suggests an important role of the polycystins in cardiac development and myocardial function. To determine whether ADPKD may predispose to the development of cardiomyopathy, we have evaluated the coexistence of diagnoses of ADPKD and primary cardiomyopathy in our patients. Methods: Clinical data were retrieved from medical records for patients with a coexisting diagnosis of ADPKD and cardiomyopathies evaluated at the Mayo Clinic (1984–2015). Results: Among the 58 of 667 patients with available echocardiography data, 39 (5.8%) had idiopathic dilated cardiomyopathy (IDCM), 17 (2.5%) had hypertrophic obstructive cardiomyopathy, and 2 (0.3%) had left ventricular noncompaction. Genetic data were available for 19, 8, and 2 cases of IDCM, hypertrophic obstructive cardiomyopathy, and left ventricular noncompaction, respectively. PKD1 mutations were detected in 42.1%, 62.5%, and 100% of IDCM, hypertrophic obstructive cardiomyopathy, and left ventricular noncompaction cases, respectively. PKD2 mutations were detected only in IDCM cases and were overrepresented (36.8%) relative to the expected frequency in ADPKD (15%). In at least 1 patient from 3 IDMC families and 1 patient from a hypertrophic obstructive cardiomyopathy family, the cardiomyopathy did not segregate with ADPKD, suggesting that the PKD mutations may be predisposing factors rather than solely responsible for the development of cardiomyopathy. Discussion: Coexistence of ADPKD and cardiomyopathy in our tertiary referral center cohort appears to be higher than expected by chance. We suggest that PKD1 and PKD2 mutations may predispose to primary cardiomyopathies and that genetic interactions may account for the observed coexistence of ADPKD and cardiomyopathies