[Nephrogenic systemic fibrosis and use of MR contrast media]. / Nefrogen systemisk fibrose ved bruk av MR-kontrastmiddel.

BACKGROUND: Nephrogenic systemic fibrosis (NSF) is a new and probably iatrogenic disorder. It was first described time in 2000 and associated with the use of gadolinium containing MR contrast media in patients with impaired renal function in 2006. MATERIAL AND METHOD: We describe a case of NSF identified at Haukeland University Hospital and give a brief overview of the disease, based on literature retrieved from a non-systematic search. RESULTS AND INTERPRETATION: NSF is a serious systemic disorder with active inflammation and fibrosis, particularly in skin, but also in other tissue such as skeletal muscle, heart and oesophagus. The condition is very difficult to treat. Awareness of the illness has led to changes in guidelines and clinical practice regarding use of gadolinium-containing contrast media in patients with renal impairment.

Glomerular charge barrier and development of proteinuria in passive Heymann nephritis.

BACKGROUND/AIM: Passive Heymann nephritis (PHN) in rats is a commonly used model of membranous glomerulonephritis in man where the cause of proteinuria is not fully resolved. This study was designed to investigate the role of the glomerular charge barrier in development of PHN proteinuria. METHODS: We studied female Sprague-Dawley rats (n = 33) at days 0, 2, 5 and 14 after induction of PHN by injection of antiserum against renal tubular epithelial antigens (anti-Fx1A). Measuring clearance of chymotrypsinogen A (Chym, MW 25,000, 21 A) and similar sized anionic chymotrypsinogen (aChym), together with (51)Cr-EDTA, we hypothesized an increased sieving coefficient (theta) of aChym in the early phase of PHN due to impairment of the glomerular charge barrier. RESULTS: No proteinuria was seen at day 2 (5.8 +/- 1.4 mg/ 24 h, p > 0.05), while protein excretion increased to 23.2 +/- 2.9 mg/24 h (p < 0.05) at day 5 (84 +/- 2% albumin) and further to 544.3 +/- 51.1 mg/24 h (p < 0.01) at day 14 (60 +/- 1% albumin; p < 0.01, day 5 vs. day 14). theta aChym was similar to control at day 2 (0.49 +/- 0.03, p > 0.05), increased at day 5 to 0.62 +/- 0.02 (p < 0.01) but decreased at day 14 to 0.39 +/- 0.02 (p < 0.01). The sieving coefficient of Chym (theta Chym) was decreased at day 14 (p < 0.05). The ratio of theta aChym to theta Chym was increased at day 5 (p < 0.01) but was elsewhere similar to control. CONCLUSION: The increased ratio of theta aChym to theta Chym and selective albuminuria at day 5 indicates an initial impairment of the glomerular charge barrier in PHN.

Glomerular charge selectivity is impaired in hypertensive nephropathy.

BACKGROUND: In hypertensive nephropathy the morphological changes and albuminuria seem to start in the inner cortex but the mechanism of proteinuria is unknown. We tested the hypothesis of reduced glomerular charge selectivity in the juxtamedullary cortex of old spontaneously hypertensive rats (SHR) as a cause of proteinuria in rats with hypertensive nephropathy. METHODS: The glomerular charge barrier was evaluated in 80-week-old SHR and age-matched normotensive Wistar-Kyoto rats (WKY) by measuring the glomerular clearance of radiolabelled cationic and anionic chymotrypsinogen (Chym and aChym, MW 25,000) accumulated by the proximal tubular cells in the outer, middle and inner cortex following intravenous injection. The glomerular filtration rates (GFR) in the cortical zones were obtained by aprotinin (MW 6500) and the sieving coefficient (theta) of the protein tracers calculated as their glomerular clearance/GFR. RESULTS: The theta aChym was similar in SHR and WKY except in the inner cortex where it was 35% higher in SHR (0.65+/-0.05) than in WKY (0.48+/-0.03) (P = 0.01). The ratio of theta aChym to theta Chym was increased from 0.55+/-0.06 to 0.77+/-0.05 (P<0.02) in the inner cortex of SHR, whereas theta Chym remained the same in all cortical zones. Finally, the percentage of glomeruli with adsorption droplets in podocytes quantified by light microscopy was higher in the inner than the outer cortex of SHR (P<0.05). CONCLUSIONS: The study supports the theory of a functioning glomerular charge barrier. An increased relative clearance of aChym in the inner cortex of SHR indicates impairment of the charge barrier, which, at least in part, could explain the increased protein excretion in SHR with hypertensive nephropathy.

Renal hemodynamics during development of hypertension in young spontaneously hypertensive rats.

BACKGROUND/AIMS: Cross-transplantation studies between animals with genetic hypertension and normotensive animals indicate a key role of the kidney in development of hypertension, and studies in young spontaneously hypertensive rats (SHR) have shown reduced glomerular filtration rate (GFR) and renal blood flow (RBF) for a short period at the age of 4-6 weeks during blood pressure increase. We tested the hypothesis that a decline in GFR during development of hypertension in SHR might be more pronounced in juxtamedullary cortex than other cortical zones. METHODS: By use of the aprotinin method, total and zonal cortical GFR was measured in anaesthetized Wistar-Kyoto (WKY) rats and SHR at the ages of 2, 4, 6, 8 and 10 weeks. RBF was measured by a transit time flowmeter. RESULTS: Body and kidney weights in SHR and WKY were not significantly different in any age group (p >0.05). Mean arterial blood pressure (MAP) was not different at the age of 2 weeks (79 +/- 6 mm Hg in SHR and 74 +/- 5 mm Hg in WKY, p > 0.05), but was significantly higher in 4-week-old SHR (104 +/- 1 mm Hg) compared to 4-week-old WKY (77 +/- 3 mm Hg) (p < 0.01). The difference in blood pressure increased with age from 4 to 10 weeks. RBF, total GFR, and outer, middle, and inner cortical GFR increased with age but were not different in SHR and WKY in any age group (p >0.05). Renal vascular resistance was increased from 4 weeks of age in SHR (21.5 +/- 1.8), significantly higher than WKY (14.4 +/- 0.9 mm Hg x ml(-1) x min.g) (p < 0.01) and stayed at higher values in older age groups (p < or = 0.01). CONCLUSION: RBF, total and zonal GFR are not significantly different in anaesthetized SHR compared to WKY at ages from 2 to 10 weeks and GFR in juxtamedullary cortex is not decreased in SHR during onset of hypertension. The results from the present study indicate that development of hypertension cannot be explained by a temporary decline in RBF or total or zonal GFR.

Age-dependent regulation of vasopressin V1a receptors in preglomerular vessels from the spontaneously hypertensive rat.

Experiments were performed to get insight into the role of AVP receptor V(1a) regulation with age, i.e., during development and maintenance of high blood pressure. Previous studies showed an increased gene expression and renal vascular response to AVP in young spontaneously hypertensive rats (SHR). The age regulation of the V(1a) receptor was examined in preglomerular vessels from 5-, 10-, 20-, and 70-wk-old SHR using normotensive Wistar-Kyoto rats (WKY) as controls. Real-time PCR and ligand binding were used for analysis of receptor expression, and the change in cytosolic calcium concentration during stimulation of isolated preglomerular vessels with AVP was studied. Studies showed an increase of the V(1a) receptor protein and mRNA from 5-and 10-wk-old SHR compared with vessels from 20- and 70-wk-old SHR. In 5-wk-old SHR receptor density was 84 +/- 13 fmol/mg protein, and 38 +/- 11 fmol/mg protein in 70-wk-old SHR (P < 0.05). mRNA in the 5- and 70-wk-old SHR was 15,854 +/- 629 and 3,181 +/- 224 V(1a) mRNA/108 18S ribosomal RNA, respectively (P < 0.001). Values from WKY at all ages were similar to 20- and 70-wk-old SHR. During stimulation with AVP, the change in cytosolic calcium in vessels from 5-wk-old SHR increased 234 +/- 59 nM, whereas the increase was 89 +/- 9 nM in 70-wk-old SHR (P = 0.03). These results indicate that the V(1a) receptor is increased at protein and mRNA level during development of hypertension in SHR but is normalized when hypertension is established.