Dr. George Vasquez Rios (@GeorgeVasquezR2) is a graduate of the clinician-scientist track in Nephrology and Glomerular Disease at the Icahn School of Medicine at Mount Sinai. His research focuses on novel biomarkers, prognostic models of kidney disease, and subphenotype discovery, which has garnered recognition from the NIH/NIDDK, ASN, the NYSN, and the AFMR. He is dedicated to advancing his career as a nephrologist at the intersection of community care and academia, with a specific emphasis on glomerular diseases, precision medicine, and inclusive clinical trials. Dr Vasquez Rios is a 2023-24 AJKD Editorial Intern.

Kidney cysts are frequently observed across a spectrum of kidney conditions. We know that their presence in young or middle-aged individuals may raise concerns regarding genetically mediated kidney diseases, such as Autosomal Dominant Polycystic Kidney Disease or certain benign forms of Autosomal Dominant Tubulointerstitial Kidney Disease. Furthermore, the complex biology of cyst formation may be linked to a wide array of cellular processes affecting critical structural elements (e.g. ciliopathies) and protective tumor suppressive pathways, such as in the case of Von Hippel-Lindau disease or Tuberous Sclerosis, which can be well identified based on the integration of genetics and clinical profiles. Conversely, kidney cysts in the older adult population are less understood, and often overlooked by clinicians. Usually, acquired simple cysts in these individuals have been associated with aging, hyperfiltration, or remote ischemic events. However, it is unknown whether there is a relationship between kidney cyst number and/or type (cortical versus medullary) and the risk of kidney disease progression in those patients who underwent contralateral kidney nephrectomy.

In the study by Sabov et al, the authors retrospectively explored this question by evaluating patients who underwent total radical nephrectomy due to renal cell carcinoma. The anatomical and histological characteristics were obtained from the non-tumor-invaded kidney tissue to establish baseline measures of kidney disease (glomerulosclerosis, IFTA, etc.) and the morphometric characteristics of the cysts located in the remaining kidney. The association between these measures and kidney disease progression, defined by a composite outcome of sustained 40% decline in eGFR, GFR<10 mL/min per 1.73 m², or transition to kidney replacement therapy support, was evaluated via several models that accounted for traditional risk factors for kidney disease progression, which were adjusted sequentially.

Out of 1,195 patients, 50 patients developed the composite outcome over a median follow-up period of 4.4 years. Among the most salient findings, the authors reported that a higher number of cysts (cortical or medullary) were independently associated with CKD events. Further analysis revealed that the association between cortical cysts and advancing kidney disease was attenuated by traditional risk factors for CKD, suggesting that these could reflect processes related to aging or fibrosis. Interestingly, the presence of two or more medullary cysts was independently associated with a fourfold increase in the risk of CKD progression compared to not having medullary cysts. While cortical cysts correlated with glomerulosclerosis and IFTA, medullary cysts had only a modest correlation with chronicity on histology. The authors raised concerns about pathways other than fibrosis or tissue remodeling leading to such associations.

Despite the limitations intrinsic to the nature of retrospective cohort studies, relatively stringent inclusion criteria, and immortal time bias, among others, these findings are relevant and worthy of further investigation in larger multicentric analyses. Ideally, as the authors indicate, these studies could include genetic analyses to identify variants responsible for cystogenesis, covert ADTKD, or other latent forms of kidney disease associated with cystic manifestations. Certainly, the next time I evaluate a patient with acquired cystic kidney disease who has undergone total radical nephrectomy due to RCC, I will devote extra attention to examining the cystic phenotype.

Clinical approach to cyst evaluation, © Vasquez Rios.

– Post prepared by George Vasquez Rios (@GeorgeVasquezR2)

To view Sabov et al (subscription required), please visit AJKD.org.
Title: Association of Kidney Cysts With Progressive CKD After Radical Nephrectomy
Authors: Moldovan Sabov, Aleksandar Denic, Aidan F. Mullan, Anthony C. Luehrs, Timothy L. Kline, Bradley J. Erickson, Theodora A. Potretzke, R. Houston Thompson, Vidit Sharma, Peter C. Harris, and Andrew D. Rule
DOI: 10.1053/j.ajkd.2023.11.016