Iodinated contrast media inhibit oxygen consumption in freshly isolated proximal tubular cells from elderly humans and diabetic rats: Influence of nitric oxide

Peter Hansell,Angelica Fasching,Fredrik Palm,Per Liss

doi:10.3109/03009734.2016.1144664

Peter Hansell, Angelica Fasching + Show 2 more

Open Access

https://doi.org/10.3109/03009734.2016.1144664

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Abstract

Objectives Mechanisms underlying contrast medium (CM)-induced nephropathy remain elusive, but recent attention has been directed to oxygen availability. The purpose of this study was to evaluate the effect of the low-osmolar CM iopromide and the iso-osmolar CM iodixanol on oxygen consumption (QO2) in freshly isolated proximal tubular cells (PTC) from kidneys ablated from elderly humans undergoing nephrectomy for renal carcinomas and from normoglycemic or streptozotocin-diabetic rats.Materials PTC were isolated from human kidneys, or kidneys of normoglycemic or streptozotocin-diabetic rats. QO2 was measured with Clark-type microelectrodes in a gas-tight chamber with and without each CM (10 mg I/mL medium). L-NAME was used to inhibit nitric oxide (NO) production caused by nitric oxide synthase.Results Both CM reduced QO2 in human PTC (about –35%) which was prevented by L-NAME. PTC from normoglycemic rats were unaffected by iopromide, whereas iodixanol decreased QO2 (–34%). Both CM decreased QO2 in PTC from diabetic rats (–38% and –36%, respectively). L-NAME only prevented the effect of iopromide in the diabetic rat PTC.Conclusions These observations demonstrate that CM can induce NO release from isolated PTC in vitro, which affects QO2. Our results suggest that the induction of NO release and subsequent effect on the cellular oxygen metabolism are dependent on several factors, including CM type and pre-existing risk factors for the development of CM-induced nephropathy.

Highlights

Contrast medium (CM)-induced nephropathy (CIN) is the third leading cause of acute renal failure in patients who have been admitted to the hospital, accounting for 10% of all cases [1,2]
Isolated human proximal tubular cells (PTC) were unaffected by L-NAME alone, whereas both iopromide and iodixanol significantly reduced QO2 (Figure 1)
PTC isolated from diabetic rats had increased baseline QO2 compared with corresponding controls (Figure 2)

Summary

Introduction

Contrast medium (CM)-induced nephropathy (CIN) is the third leading cause of acute renal failure in patients who have been admitted to the hospital, accounting for 10% of all cases [1,2]. The underlying causes of CIN remain to be established, but several mechanisms have been suggested, with hypoxic insults to the renal medulla dominating the arena [3,4]. Due to the vascular architecture of the renal medulla with countercurrent exchange vessels (vasa recta) the oxygen availability is low already during normal physiological conditions. Pre-existing renal impairment is a well-established risk factor for the development of CIN. It has been suggested that CM may cause medullary hypoxia which results in the development of CIN. A combination of various mechanisms is responsible for the development of CIN [4], but the pathophysiological relevance of direct effects of CM on tubular cells is contentious [8], as are the other proposed etiologies [4,9]

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