Hyperfiltration can be detected by transcutaneous assessment of glomerular filtration rate in diabetic obese mice.

We addressed if hyperfiltration can be assessed transcutaneously in male diabetic obese mice (BTBRob/ob) at 12 and 24 wk and how this relates to glomerular parameters indicative for hyperfiltration. Transcutaneous assessment of FITC-Sinistrin clearance [transcutaneous assessment of glomerular filtration rate (tGFR)] was compared against classical plasma clearance. Kidney from SV620C-01-PEI perfused mice were harvested at 24 wk and processed for tissue clearing and classical histology. Perfusion patterns of glomerular capillaries, glomerular size, and vasodilation of the afferent arterioles were assessed. Although at 12 wk FITC-Sinistrin half-life (t1/2) for both tGFR and plasma clearance suggested hyperfiltration, this was not significant anymore at 24 wk. In kidneys of diabetic mice the diameter of the afferent arteriole was significantly larger and positively correlated with glomerular size. Glomerular perfusion pattern in these mice was heterogeneous ranging from non- to well-perfused glomeruli. Nonperfused glomerular areas displayed a strong periodic acid-Schiff's (PAS) positive staining. Collectively our data demonstrate that tGFR is a valid method to detect hyperfiltration. Hyperfiltration occurs early in BTBRob/ob mice and disappears with disease progression as a consequence of a reduced filtration surface. It remains to be assessed if tGFR is also a valid method in diabetic mice with severely compromised renal function.NEW & NOTEWORTHY tGFR measurement is a relatively new method to assess kidney function in conscious rodents, which can be repeated multiple times in the same animal to track the course of the disease and/or the effect of potential treatments. Since the literature was inconclusive on the suitability of this technique in obese mice, we validated it for the first time against classical plasma clearance in the commonly used BTBRob/ob mouse model.

Investigation of Different Methods of Intraoperative Graft Perfusion Assessment during Kidney Transplantation for the Prediction of Delayed Graft Function: A Prospective Pilot Trial.

Delayed graft function (DGF) after renal transplantation is a relevant clinical problem affecting long-term organ function. The early detection of patients at risk is crucial for postoperative monitoring and treatment algorithms. In this prospective cohort study, allograft perfusion was evaluated intraoperatively in 26 kidney recipients by visual and formal perfusion assessment, duplex sonography, and quantitative microperfusion assessment using O2C spectrometry and ICG fluorescence angiography. The O2C tissue spectrometry device provides a quantitative method of microperfusion assessment that can be employed during kidney transplantation as an easy-to-use and highly sensitive alternative to ICG fluorescence angiography. Intraoperative microvascular flow and velocity in the allograft cortex after reperfusion predicted DGF with a sensitivity of 100% and a specificity of 82%. Threshold values of 57 A.U. for microvascular flow and 13 A.U. for microvascular velocity were identified by an ROC analysis. This study, therefore, confirmed that impairment of microperfusion of the allograft cortex directly after reperfusion was a key indicator for the occurrence of DGF after kidney transplantation. Our results support the combined use of intraoperative duplex sonography, for macrovascular quality control, and quantitative microperfusion assessment, such as O2C spectrometry, for individual risk stratification to guide subsequent postoperative management.

Area-based socioeconomic status and mortality: the Ludwigshafen Risk and Cardiovascular Health study.

BACKGROUND: Low individual socioeconomic status (SES) is a known risk factor for morbidity and mortality. A related measure is the area-based SES (abSES), which describes the average SES of a region. The association of measures of abSES with morbidity and mortality is less well studied. METHODS: The Ludwigshafen Risk and Cardiovascular Health study consists of 3316 patients hospitalized for coronary angiography between 1997 and 2000 at a tertiary care centre in Germany. Patients were followed up for a median of 10 years. Two measures of abSES were used: the regional purchasing index (PPI, data obtained from IQVIA GmbH) and the German Index of Socioeconomic Deprivation (GISD, developed by the Robert-Koch Institute). The association of abSES with disease and with mortality was analysed using logistic regression and Cox proportional hazards regression, respectively. RESULTS: Study participants living in regions with higher abSES had lower HbA1c and high-sensitive C-reactive protein. A higher abSES was associated with lower prevalence of active smoking, vitamin D deficiency and diabetes mellitus. We further found significantly increased mortality for participants in the lowest PPI quartile (age- and sex-adjusted hazard ratio (95% CI) of 0.58 (0.38-0.90) as compared to the first quartile), and in the highest GISD tertile (HR of 1.32 (1.13-1.54) as compared to the first tertile). CONCLUSION: Living in an area with a low abSES was associated with a higher burden of diabetes mellitus, a higher percentage of severe vitamin D deficiency, higher systemic inflammation and a significant increase in mortality.

Quantitative assessment of microperfusion by indocyanine green angiography in kidney transplantation resembles chronic morphological changes in kidney specimens.

OBJECTIVE: ICG fluorescence angiography enables a quantitative real-time perfusion assessment in kidney transplantation. The results of intraoperative microperfusion of the kidney allograft were compared to the renal chronicity score in pre-transplantation kidney biopsy specimens. The intrarenal resistance index was calculated by duplex sonography as a method of reference. METHODS: Seventy-seven patients with end-stage renal disease undergoing kidney transplantation were prospectively included in two centers. Correlation analysis of chronic changes in kidney biopsy specimens and the IN of ICG fluorescence signal were investigated. RESULTS: The results yielded a significantly negative correlation for the renal chronicity (r = -0.294, P = 0.017) as well as the intestinal fibrosis and tubular atrophy score (r = -0.328, P = 0.007). There was a significant inverse relationship between the IN and the mean RI values of the upper pole of the kidney allograft. CONCLUSIONS: In summary, fluorescence angiography reflects preexisting morphological changes of the renal cortex. ICG angiography may serve as an alternative method for the assessment of microperfusion of the kidney allograft.

Renal Denervation in Patients with Resistant Hypertension-Assessment by 3T Renal 23Na-MRI: Preliminary Results.

BACKGROUND/AIM: Renal denervation (RDN) has been considered a promising therapy option for patients suffering from therapy-resistant hypertension. Besides, in blood-pressure regularization, the kidneys play a fundamental role in sodium ((23)Na) homeostasis. This study assesses the effect of RDN on renal (23)Na concentration using (23)Na magnetic resonance imaging (MRI). PATIENTS AND METHODS: Two patients with therapy-resistant hypertension underwent RDN. (23)Na-MRI, (1)H-MRI, including diffusion weighted imaging (DWI), as well as endothelial dysfunction assessment, were performed 1 day prior, as well as 1, 30 and 90 days after RDN. RESULTS: The renal corticomedullary (23)Na gradient did not change after RDN for all time points. Additionally, functional imaging and retinal vessel parameters were not influenced by RDN. Results regarding blood pressure changes and arterial stiffness, as well as patients' clinical outcome, were heterogeneous. CONCLUSION: RDN does not seem to alter renal (23)Na concentration gradients, as measured by MRI.

Long-term results of pancreas transplantation in patients older than 50 years.

Aging of the population and improvements in diabetes therapy have led to an increased number of older pancreas transplant candidates. The aim of our retrospective study was to evaluate pancreas transplantation (PT) outcomes in patients ≥ 50 years, as limited data exist in these patients. We analyzed 398 consecutive pancreas transplant patients from June 1994 to June 2009 for different outcomes (patient/graft survival, rejection rate, and surgical complications) between the age groups ≥ 50 years (n = 69) and <50 years (n = 329). Donor and recipient characteristics were similar except for recipient age (54.0 vs. 38.8 years), BMI (24.6 vs. 22.9 kg/m(2) ), and duration of diabetes mellitus (36.0 vs. 27.7 years). One-, 5-, and 10-year patient and graft (kidney/pancreas) survival were not significantly different between the groups with patient survival rates reaching 84% and pancreas graft survival up to 67% after 10 years. Surgical complications such as relaparotomy rate (34% vs. 33%) or pancreas graft thrombosis (14% vs. 11%) as well as 1-year rejection rates (35% vs. 31%) were not significantly different. PT in selected patients aged ≥ 50 years resulted in survival comparable with that of younger patients. In conclusion, advanced age should no longer be considered as an exclusion criterion for PT. However, good medical assessment and careful patient selection are necessary.

Effect of chronic kidney disease and comorbid conditions on health care costs: A 10-year observational study in a general population.

BACKGROUND: Chronic kidney disease (CKD) is common, but the longitudinal effects of CKD and associated comorbidities on health care costs in the general population are unknown. METHODS: Population-based cohort study of 2,988 subjects in Germany, aged 25-74 years at baseline, who participated both in the baseline and 10-year follow-up examination (1994/95-2004/05). Presence of CKD was based on serum creatinine and defined as an estimated glomerular filtration rate of <60 ml/min/1.73 m(2). Self-reported health services utilization was used to estimate costs. RESULTS: Health care costs at baseline and follow-up were higher for subjects with CKD. Controlling for socio-economics, lifestyle factors and comorbid conditions, subjects with baseline CKD, in comparison to those without, exhibited 65% higher total costs 10 years after baseline examination, corresponding to a difference in adjusted costs of EUR 743. Incident CKD was related to 38% higher total costs. Costs for inpatient treatment and drug costs were the major costs components, while CKD revealed no effect on outpatient costs. The effect of CKD was strongly modified by angina, myocardial infarction, diabetes, and anemia. CONCLUSIONS: The direct effect of CKD on costs is modified by comorbid conditions. Therefore, early treatment of CKD and its precipitous factors may save future health care costs.