Dahl, Neera K.

Key Points Kidney stones are common in patients with autosomal dominant polycystic kidney disease compared with matched controls with CKD. The increase in imaging seen in patients with autosomal dominant polycystic kidney disease correlates with the kidney stone burden in these patients. Background Patients with autosomal dominant polycystic kidney disease (ADPKD) may have more imaging studies than patients with other forms of CKD. We characterized the imaging burden of patients with ADPKD relative to a CKD population to determine which factors lead to increased imaging in patients with ADPKD. Methods We retrospectively reviewed patients seen at Yale Nephrology between January 2012 and January 2021. We collected demographic, clinical, and imaging data through automated query and manual chart review. Eight hundred seven patients with ADPKD were matched to 4035 CKD controls on the basis of criteria of sex, race, ethnicity, CKD stage, hypertension, and diabetes, but not age. The number of abdominal imaging studies were compared between ADPKD and CKD groups, and the effect of kidney stone diagnosis was further evaluated. Chi-square and t tests were used to evaluate demographic variables, and Kruskal Wallis and negative binomial regression models were used to evaluate differences between abdominal imaging studies. Results Patients with ADPKD had a greater number of total abdominal imaging studies ( P < 0.0001), ultrasounds ( P < 0.0001), and magnetic resonance imagings ( P = 0.02) compared with controls. In patients with preserved renal function (eGFR >60 ml/min per m 2 ), these differences persisted. Kidney stones were significantly more common among patients with ADPKD ( P < 0.0001). In multivariable assessment of imaging study counts using a negative binomial model controlling for kidney stones, ADPKD was no longer a significant predictor. In patients with ADPKD, pyelonephritis; cyst complications; lower eGFR; diabetes; coronary artery disease; kidney stones; lower body mass index; and being male, Black, and younger increased the likelihood of having more imaging studies. Conclusions The higher prevalence of abdominal imaging studies in patients with ADPKD correlated with the increased incidence of kidney stones observed in this population.

Patients with autosomal dominant polycystic kidney disease benefit from specialized care over their lifetimes, starting with diagnosis of the condition with ongoing discussion of both the renal course and extra-renal issues. Both renal and extra-renal issues may continue to cause major morbidity even after successful kidney transplant or initiation of RRT, and extra-renal disease aspects should always be considered as part of routine management. In this review, we will focus on updates in pain/depression screening, cardiac manifestations, liver and pancreatic cysts, kidney stone management, and genetic counseling. In some instances, we have shared our current clinical practice rather than an evidence-based guideline. We anticipate more standardization of care after the release of the Kidney Disease Improving Global Outcomes guidelines for management in autosomal dominant polycystic kidney disease later this year.

Genetic testing in nephrology is becoming increasingly important to diagnose patients and to provide appropriate care. This is especially true for autosomal dominant polycystic kidney disease (ADPKD) because this is a common cause of kidney failure and genetically complex. In addition to the major genes, PKD1 and PKD2 , there are at least six minor loci, and phenotypic, and in some cases, genetic overlap with other cystic disorders. Targeted next-generation sequencing, a low-cost, high-throughput technique, has made routine genetic testing viable in nephrology clinics. Appropriate pre- and post-testing genetic counseling is essential to the testing process. Carefully assessing variants is also critical, with the genetic report classifying variants in accordance with American College of Medical Genetics and Genomics guidelines. However, variant of uncertain significance (VUSs) may pose a significant challenge for the ordering clinician. In ADPKD, and particularly within PKD1 , there is high allelic heterogeneity; no single variant is present in more than 2% of families. The Mayo/Polycystic Kidney Disease Foundation variant database, a research tool, is the best current database of PKD1 and PKD2 variants containing over 2300 variants identified in individuals with polycystic kidney disease, but novel variants are often identified. In patients with a high pretest probability of ADPKD on the basis of clinical criteria, but no finding of a pathogenic (P) or likely pathogenic (LP) variant in a cystic kidney gene, additional evaluation of cystic gene VUS can be helpful. In this case-based review, we propose an algorithm for the assessment of such variants in a clinical setting and show how some can be reassigned to a diagnostic grouping. When assessing the relevance of a VUS, we consider both patient/family-specific and allele-related factors using population and variant databases and available prediction tools, as well as genetic expertise. This analysis plus further family studies can aid in making a genetic diagnosis.