Nephrogenic systemic fibrosis is a new, rare disease of unknown cause that affects patients with renal failure. Single cases led to the suspicion of a causative role of gadodiamide that is used for magnetic resonance imaging. This study therefore reviewed all of the authors' confirmed cases of nephrogenic systemic fibrosis (n ‫؍‬ 13) with respect to clinical characteristics, gadodiamide exposure, and subsequent clinical course. It was found that all had been exposed to gadodiamide before the development of nephrogenic systemic fibrosis. The delay from exposure to first sign of the disease was 2 to 75 d (median 25 d). Odds ratio for acquiring the disease when gadodiamide exposed was 32.5 (95% confidence interval 1.9 to 549.2; P < 0.0001). Seven (54%) patients became severely disabled, and one died 21 mo after exposure. No other exposure/event than gadodiamide that was common to more than a minority of the patients could be identified. These findings indicate that gadodiamide plays a causative role in nephrogenic systemic fibrosis. , previously known as nephrogenic fibrosing dermopathy, have been reported worldwide (1,2). The appearance of this new and serious disease has triggered considerable interest as to possible causative factors, including newly introduced clinical practices. However, until now, the eliciting factor(s) has not been identified. Mendoza et al. (3) recently reviewed the clinical picture of NSF. The typical patient is middle-aged and has ESRD. Most but not all are on regular dialysis treatment. The typical course begins with subacute swelling of distal parts of the extremities and is followed in subsequent weeks by severe skin induration and sometimes anatomic extension to involve thighs, antebrachium, and lower abdomen. The skin induration may be aggressive and associated with constant pain, muscle restlessness, and loss of skin flexibility. In some cases, NSF leads to serious physical disability, including wheelchair requirement. NSF initially was observed in and thought to affect solely the skin (thus the initial term nephrogenic fibrosing dermopathy), but more recent patient reports have demonstrated that several organs may be involved. Organ involvement may explain the suspected increased mortality of patients with NSF (3). There is no established treatment for NSF, but some cases have been reported to improve after kidney transplantation, and others seem to have been treated successfully with extracorporeal photopheresis (4).At the department of nephrology, Copenhagen University Hospital at Herlev, we became aware of a formerly unknown skin disease among our patients with ESRD during 2002 through 2005. Skin biopsies supported the clinical suspicion of NSF. Some of the case stories strongly indicated that the skin changes were elicited by contrast-enhanced magnetic resonance imaging (MRI). Since late 2001, we have used this method frequently for patients with ESRD, in particular for description of iliac and lower limb arteries before kidney transplantation (5). During the past 5 to 10 yr,...

To elucidate the causes of the diminished incretin effect in type 2 diabetes mellitus we investigated the secretion of the incretin hormones, glucagon-like peptide-1 and glucose- dependent insulinotropic polypeptide and measured nonesterified fatty acids, and plasma concentrations of insulin, C peptide, pancreatic polypeptide, and glucose during a 4-h mixed meal test in 54 heterogeneous type 2 diabetic patients, 33 matched control subjects with normal glucose tolerance, and 15 unmatched subjects with impaired glucose tolerance. The glucagon-like peptide-1 response in terms of area under the curve from 0-240 min after the start of the meal was significantly decreased in the patients (2482 +/- 145 compared with 3101 +/- 198 pmol/liter.240 min; P = 0.024). In addition, the area under the curve for glucose-dependent insulinotropic polypeptide was slightly decreased. In a multiple regression analysis, a model with diabetes, body mass index, male sex, insulin area under the curve (negative influence), glucose-dependent insulinotropic polypeptide area under the curve (negative influence), and glucagon area under the curve (positive influence) explained 42% of the variability of the glucagon-like peptide-1 response. The impaired glucose tolerance subjects were hyperinsulinemic and generally showed the same abnormalities as the diabetic patients, but to a lesser degree. We conclude that the meal-related glucagon-like peptide-1 response in type 2 diabetes is decreased, which may contribute to the decreased incretin effect in type 2 diabetes.

ObjectiveTo investigate associations between pre-eclampsia and later risk of kidney disease.DesignNationwide register based cohort study.SettingDenmark.PopulationAll women with at least one pregnancy lasting at least 20 weeks between 1978 and 2015.Main outcome measureHazard ratios comparing rates of kidney disease between women with and without a history of pre-eclampsia, stratified by gestational age at delivery and estimated using Cox regression.ResultsThe cohort consisted of 1 072 330 women followed for 19 994 470 person years (average 18.6 years/woman). Compared with women with no previous pre-eclampsia, those with a history of pre-eclampsia were more likely to develop chronic renal conditions: hazard ratio 3.93 (95% confidence interval 2.90 to 5.33, for early preterm pre-eclampsia (delivery <34 weeks); 2.81 (2.13 to 3.71) for late preterm pre-eclampsia (delivery 34-36 weeks); 2.27 (2.02 to 2.55) for term pre-eclampsia (delivery ≥37 weeks). In particular, strong associations were observed for chronic kidney disease, hypertensive kidney disease, and glomerular/proteinuric disease. Adjustment for cardiovascular disease and hypertension only partially attenuated the observed associations. Stratifying the analyses on time since pregnancy showed that associations between pre-eclampsia and chronic kidney disease and glomerular/proteinuric disease were much stronger within five years of the latest pregnancy (hazard ratio 6.11 (3.84 to 9.72) and 4.77 (3.88 to 5.86), respectively) than five years or longer after the latest pregnancy (2.06 (1.69 to 2.50) and 1.50 (1.19 to 1.88). By contrast, associations between pre-eclampsia and acute renal conditions were modest.Conclusions Pre-eclampsia, particularly early preterm pre-eclampsia, was strongly associated with several chronic renal disorders later in life. More research is needed to determine which women are most likely to develop kidney disease after pre-eclampsia, what mechanisms underlie the association, and what clinical follow-up and interventions (and in what timeframe post-pregnancy) would be most appropriate and effective.