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Biomedical subjects

Niels Marcussen

Publications and source records attributed to Niels Marcussen.

23 records · Page 2Linked to original sources

Effects of renal denervation on tubular sodium handling in rats with CBL-induced liver cirrhosis.

This study was designed to examine the effect of bilateral renal denervation (DNX) on thick ascending limb of Henle's loop (TAL) function in rats with liver cirrhosis induced by common bile duct ligation (CBL). The CBL rats had, as previously shown, sodium retention associated with hypertrophy of the inner stripe of the outer medulla (ISOM) and increased natriuretic effect of furosemide in vivo, and semiquantitative immunoblotting showed increased expression of the furosemide-sensitive Na-K-2Cl cotransporter type 2 (NKCC2) in ISOM from CBL rats. DNX significantly attenuated the sodium retention in the CBL rats, which was associated with normalization of the natriuretic effect of furosemide, as well as a significant reduction in the expression of NKCC2 in the ISOM. However, the marked hypertrophy of the ISOM found in CBL rats was not reversed by DNX. Together, these data indicate that increased renal sympathetic nerve activity known to be present in CBL rats plays a significant role in the formation of sodium retention by stimulating sodium reabsorption in the TAL via increased renal abundance of NKCC2.

Aldosterone↗

Renal structural abnormalities following recovery from acute puromycin nephrosis.

BACKGROUND: Rats that recover from acute puromycin nephrosis later develop widespread glomerular and tubulointerstitial injury. The current study sought to identify structural changes present in the recovery phase that could precipitate progressive renal disease. METHODS: Stereologic studies were performed 10 weeks after administration of puromycin (PAN) or saline (Cont). Serial sections were examined to assess glomerular structure. RESULTS: Rats receiving puromycin developed heavy proteinuria that returned nearly to control levels at 10 weeks. Kidneys in these animals were moderately enlarged and exhibited expansion of the interstitium (PAN, 254 +/- 47 mm3; Cont, 152 +/- 23 mm3; P < 0.05). The average glomerular volume was not different from control (PAN, 1.90 +/- 0.38 x 10(6) microm3; Cont, 2.07 +/- 0.47 x 10(6) microm3), but a subpopulation of glomeruli of about half normal size was found in PAN rats. Serial sections revealed that most of these glomeruli were not connected to normal tubule segments. Serial sections also revealed that more than 90% of glomeruli in rats recovering from nephrosis had synechias joining the tuft to Bowman's capsule. Synechias occupied an average of 8 +/- 11% of the Bowman's capsule surface in PAN animals versus less than 1% of the surface in controls. The appearance of synechias was not associated with a reduction in the mean number of visceral or parietal epithelial cells per glomerulus. CONCLUSIONS: Acute puromycin nephrosis does not cause a notable reduction in visceral epithelial cell number. However, widespread glomerular injury characterized by synechia between the tuft and Bowman's capsule is present following remission of proteinuria. Progression of this residual glomerular injury could contribute to the late development of glomerular segmental sclerosis following recovery from acute nephrosis.

Acute Disease↗

Measurements of cortical interstitium in biopsies from human kidney grafts: how representative and how reproducible?

BACKGROUND: The aim of the study was to evaluate how well a biopsy from one region of a human renal allograft represented biopsies from other regions regarding the renal interstitial tissue assessed by stereology. Furthermore, we wanted to evaluate the reproducibility of the measurements. METHODS: Punch biopsies (3 mm) from six regions in each kidney were obtained from seven explanted renal grafts with varying degrees of clinically diagnosed chronic and acute rejection. One kidney, removed for a minor pelvic tumour, served as reference material. Using point counting on PAS-stained sections, the volume fraction of the interstitial tissue per glomerular cortex V(V)(interstitium/cortex) was estimated. From each kidney, two of the six biopsies were re-evaluated by the same observer. RESULTS: V(V)(interstitium/cortex) varied from 0.25 to 0.78 between the explanted kidneys vs 0.26 in the reference kidney. Variations within the kidneys were low, expressed by standard deviations (SD) of between 0.04 and 0.06, and coefficients of variation (CV) between 0.06 and 0.22. The SD estimated from repeated measurements was 0.04 and CV was 0.07. CONCLUSIONS: Biopsies from one region of the kidney were found to be representative for estimates of interstitial tissue in explanted human kidney grafts, and the degree of reproducibility was high when using point counting, as in the present study.

Adult↗

Losartan treatment normalizes renal sodium and water handling in rats with mild congestive heart failure.

This study was designed to examine the effect of losartan treatment on renal tubular function in rats with mild congestive heart failure (CHF) induced by ligation of the left anterior descending artery. In rats with CHF, there was a significant decrease in daily sodium excretion, which caused sodium retention relative to control rats. Renal function studies revealed that glomerular filtration rate and proximal tubular sodium handling were normal. However, expression of the Na(+)-K(+)-2Cl(-) cotransporter (NKCC2) in the thick ascending limb of Henle's loop was increased. Moreover, vasopressin-mediated renal water reabsorption, as evaluated by the aquaretic response to selective V(2)-receptor blockade, was significantly increased. Losartan treatment normalized expression of NKCC2 and decreased expression of the vasopressin-regulated water channel aquaporin-2. This was associated with normalization of daily sodium excretion and normalization of the aquaretic response to V(2)-receptor blockade. Together, these results indicate that, in rats with CHF, losartan treatment inhibits increased sodium reabsorption through NKCC2 in the thick ascending limb of Henle's loop and water reabsorption through aquaporin-2 in the collecting ducts, which may be involved in improving renal function in losartan-treated CHF rats.

Animals↗

Acute interstitial nephritis associated with the use of mesalazine in inflammatory bowel disease.

BACKGROUND: In the last 10 years several reports have linked oral 5-aminosalicylic acid (5-ASA) therapy to acute and chronic tubulointerstitial nephritis, but to our knowledge only 2 patients have been reported with terminal end-stage renal disease due to mesalazine (5-ASA). After 1 year of treatment with 5-ASA annual monitoring of serum creatinine is recommended. RESULTS: We report the development of end-stage renal disease in a patient 10 months after the last assessment of serum creatinine, which was normal at 71 micromol/l. CONCLUSION: Because of this dangerous side effect, we would like to recommend 6-monthly assessment of renal function.

Adolescent↗