Cyst fluid composition in human autosomal recessive polycystic kidney disease

Abstract

Sirs, Autosomal dominant polycystic kidney disease (ADPKD) is the most common monogenic renal disorder and frequently progresses to renal failure [1]. Because of its relative prevalence, it is the most well-characterized of the genetic cystic renal diseases. Histopathologically, the cysts are derived from all segments of the nephron, yet they “bud off” and separate from the tubule from which they are derived [1]. Cystic expansion is thought to be related to multiple biological processes including Na, Cl, and fluid secretion into cysts, processes that would tend to enlarge a discrete cyst and compress surrounding normal renal tissue [1]. Autosomal recessive polycystic kidney disease (ARPKD) is less common than ADPKD with an incidence of ~1 in 20,000 live births [1, 2]. Phenotypically, infants and children with ARPKD frequently present with hypertension, which generally appears well in advance of renal insufficiency [3]. Histologically, ARPKD is associated with ectasia and dilatation of renal collecting ducts and intra-hepatic bile ducts, and therefore does not retain the classic ADPKD “blind loop” sac-like cystic pattern [1]. We have previously examined the transepithelial Na transport properties of human ARPKD cystic epithelial cells in culture and reported that these cells absorb Na, as did normal age-matched counterparts. However, we showed, unexpectedly, that ARPKD cyst-lining cells reabsorbed Na at a rate ~50% greater than that of controls [4]. The Na absorptive flux in ARPKD cells was only modestly inhibited by high doses (100 mM) of amiloride, an inhibitor of the epithelial Na channel (ENaC) and Na-H antiporter [4]. Similar investigations of collecting duct epithelial cells derived from orpk mice, a murine model of ARPKD, suggested that these cells, like their human ARPKD counterparts, absorb Na at a higher rate than controls [5]. Based on these laboratory investigations, we were interested to determine if the in vitro studies could be validated in vivo. With institutional review board approval, we sought to characterize cyst fluid composition from ARPKD nephrectomy specimens at the time of renal transplantation. Cyst fluid (~0.1–0.3 ml samples, 8–11 samples per kidney) was collected in the operating room from freshly harvested pediatric ARPKD kidneys. Analysis of fluid aspirated from cysts within the renal parenchyma from three separate end-stage ARPKD kidney specimens revealed a low Na concentration and an osmolality similar to that of serum (Table 1). We speculate that the urine osmolality of ~300 mosmol/kg is due to the presence of urea, which was not measured. The cyst fluid R. Rohatgi Division of Nephrology, Department of Medicine, Mount Sinai School of Medicine, New York, NY 10029, USA