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

Abstract

The commonly accepted manifestations of renal insufficiency are usually not recognized in patients with autosomal dominant polycystic kidney disease (ADPKD) until the fourth decade of life (1). However, many ADPKD patients with GFRs indistinguishable from normal are unable to increase the osmolality of urine above 800 mosm/kg H 2 O after overnight dehydration or after the parenteral administration of supplementary vasopressin. 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.The baseline urine volumes, osmolar excretion rates, and plasma arginine vasopressin (AVP) and copeptin concentrations were not appreciably different between ADPKD patients and controls in this study; however, after overnight dehydration, the plasma levels of AVP and copeptin were significantly and persistently higher in the ADPKD subjects, and the urine osmolality was persistently lower than in the controls. The authors found evidence of an intact hypothalamic mechanism for the osmotic release of vasopressin, meaning that the defect must lie in the kidneys. Interestingly, ADPKD patients had higher plasma and lower urine concentrations of urea after achieving the highest elevation of urine osmolality, suggesting that urea clearance was decreased in the ADPKD patients even though eGFR was not different between study patients and control subjects. The urea excretion rate after dehydration was not reported; however, the similar baseline osmolar excretion rates make it unlikely that the urea excretion rates in the ADPKD patients were different from normal.The plasma urea levels were elevated in the ADPKD patients, possibly reflecting a decreased renal urea clearance. Because plasma sodium levels were equal in patients and control subjects, the increased urea concentration probably accounts for the consistent elevation of plasma osmolality in ADPKD patients compared with control subjects. Because urea distributes relatively freely in body water, it is unlikely that the small increase in plasma osmolality caused by increased urea concentration was responsible for the increased plasma concentrations of AVP and copeptin in the ADPKD patients. On the other hand, the restriction of water intake unquestionably increased plasma levels of vasopressin and copeptin and the reabsorption of free water in the patients, although to a lesser degree than in control subjects. A nonosmotic vasopressin releasing mechanism, e.g., extracellular fluid volume contraction, is a reasonable possibility and, in this regard, careful measurements of changes in body weight and urine volume before and after water restriction wo...

Kidney concentrating capacity in children with autosomal recessive polycystic kidney disease is linked to glomerular filtration and hypertension

“…In our previous study [6] along with further pediatric and adult studies [5,7,8,20,21], it has been shown that approximately 50% of patients with ADPKD have impaired kidney concentrating ability and reduced concentration capacity. These impairments were linked to ambulatory BP and the number of kidney cysts, but not to GFR.…”