Vasopressin, Copeptin, and Renal Concentrating Capacity in Patients with Autosomal Dominant Polycystic Kidney Disease without Renal Impairment

Abstract

SummaryBackground and objectives Autosomal dominant polycystic kidney disease (ADPKD) is the most prevalent hereditary renal disease, characterized by cyst formation in the kidneys leading to end stage kidney failure. It is clinically acknowledged that ADPKD patients have impaired urine concentrating capacity, but the mechanism behind this observation is unknown.Design, setting, participants, & measurements Fifteen ADPKD patients (estimated GFR $60 ml/min per 1.73 m 2 ) and 15 age-and sex-matched healthy controls underwent a standard prolonged water deprivation test in which urine and plasma osmolality, vasopressin, and copeptin were measured. The effect of a synthetic vasopressin analog (desmopressin) injected at the moment of maximal urine concentrating capacity was also studied.Results After 14 hours of water deprivation, ADPKD patients tended to have higher plasma osmolality (P=0.07) and significantly higher vasopressin and copeptin levels (both P,0.05), whereas urine osmolality was similar in ADPKD patients and controls (710 versus 742 mOsmol/kg; P=0.61). Maximal urine concentrating capacity was lower in ADPKD patients (758 versus 915 mOsmol/kg in controls; P,0.001). At maximal urine concentrating capacity, plasma osmolality, vasopressin, and copeptin levels were significantly higher in ADPKD patients. The median increase in urine osmolality after desmopressin administration in ADPKD patients was less than in healthy controls.Conclusions Already early in their disease, ADPKD patients have impaired maximal urine concentrating capacity brought out upon dehydration, with no evidence of impaired hypothalamic response. To maintain fluid balance, vasopressin concentration increases, which is hypothesized to play a role in ADPKD disease progression.

Vasopressin-2 Receptor Signaling and Autosomal Dominant Polycystic Kidney Disease

“…15 In ADPKD, however, it is important to distinguish an early and rather mild urinary concentration deficit from the severe urinary concentration deficit associated with many forms of ESRD in the late course of the disease. In fact, as shown by Zittema et al 11 and Gabow et al 16 in large patient cohorts, maximal urine concentration capacities (maximal urine osmolality after overnight thirsting) are reduced but remain well above serum osmolality. In addition, Zittema et al 11 showed that patients carrying a polycystic kidney disease 1 (PKD1) mutation have early urine concentration deficits and increased vasopressin/copeptin levels.…”

“…[8][9][10][11] One key advance in the past 5 years was the development of more robust and reliable assays to measure and estimate concentration of vasopressin in the serum. 12 Copeptin, a 39-amino acid glycopeptide comprising the C terminus of the vasopressin precursor (preprovasopressin), is cosecreted with vasopressin by the neurohypophysis, which is somewhat comparable with cosecretion of the C peptide and insulin by the pancreas.…”

Arginine Vasopressin Promotes Redistribution of Adhesion Junction Protein E-Cadherin in Kidney Epithelial Cells

“…10 Besides the above-mentioned pathological observations, large-scale retrospective studies suggested a high-level plasma copeptin (a surrogate of vasopressin), is associated with the progression of kidney diseases. [11][12][13][14][15] For example, positive associations were found between copeptin levels with disease severity in autosomal dominant polycystic kidney disease (ADPKD) patients. [11][12][13][14] Higher serum level of copeptin was also detected in kidney transplant recipients who have accelerated renal function decline.…”

“…[11][12][13][14][15] For example, positive associations were found between copeptin levels with disease severity in autosomal dominant polycystic kidney disease (ADPKD) patients. [11][12][13][14] Higher serum level of copeptin was also detected in kidney transplant recipients who have accelerated renal function decline. 12 From currently available literatures, it is clear that vasopressin (VP) regulates water reabsorption by a®ecting cellular distribution of a water channel protein aquaporin 2 in kidney epithelial cells; 7,[16][17][18] however, whether VP a®ects other cellular proteins that are responsible for maintaining cell polarity of kidney tubules, and as a consequence, contributes to the kidney diseases progression is unclear.…”

Bully Renal Cysts Knock Down Urine-Concentrating Capacity in the Early Rounds

“…This "concentrating defect" can be detected in some young children and young adults decades before the GFR noticeably declines, indicating that parenchymal malfunction begins very early in the course of renal cystic disease (2). In an excellent study reported in this issue of CJASN, Zittema et al (3) confirm that maximal urine concentration capacity is lost in ADPKD patients compared with normal controls. Still at issue is the mechanism(s) by which ADPKD impairs the maximal concentration of the urine.…”