The German CaRe high registry for familial hypercholesterolemia - Sex differences, treatment strategies, and target value attainment.

Background and aims: Familial hypercholesterolemia (FH) is among the most common genetic disorders in primary care. However, only 15% or less of patients are diagnosed, and few achieve the goals for low-density lipoprotein cholesterol (LDL-C). In this analysis of the German Cascade Screening and Registry for High Cholesterol (CaRe High), we examined the status of lipid management, treatment strategies, and LDL-C goal attainment according to the ESC/EAS dyslipidemia guidelines. Methods: We evaluated consolidated datasets from 1501 FH patients diagnosed clinically and seen either by lipid specialists or general practitioners and internists. We conducted a questionnaire survey of both the recruiting physicians and patients. Results: Among the 1501 patients, 86% regularly received lipid-lowering drugs. LDL-C goals were achieved by 26% and 10% of patients with atherosclerotic cardiovascular disease (ASCVD) according to the 2016 and 2019 ESC/EAS dyslipidemia guidelines, respectively. High intensity lipid-lowering was administered more often in men than in women, in patients with ASCVD, at higher LDL-C and in patients with a genetic diagnosis of FH. Conclusions: FH is under-treated in Germany compared to guideline recommendations. Male gender, genetic proof of FH, treatment by a specialist, and presence of ASCVD appear to be associated with increased treatment intensity. Achieving the LDL-C goals of the 2019 ESC/EAS dyslipidemia guidelines remains challenging if pre-treatment LDL-C is very high.

Effects of N-acetylcysteine on renal hemodynamics in contrast media-induced nephropathy.

BACKGROUND: N-acetylcysteine (NAC) has been proposed to prevent radiocontrast nephropathy in high-risk patients. METHODS: The effect of single-dose and prolonged administration of NAC before application of either the ionic, high-osmolar radiocontrast agent diatrizoate sodium (DTZ) or the nonionic, low-osmolar radiocontrast agent iohexol (IOH) in a rat model combining uninephrectomy, salt depletion, and administration of indomethacin was explored. Arterial blood pressure and total, cortical, and medullary blood flow were continuously recorded in anesthetized Sprague-Dawley rats. RESULTS: NAC had no effect on renal hemodynamics in control rats. Both DTZ and IOH induced biphasic changes in renal blood flow and cortical renal blood flux and persistently reduced medullary blood flux. Neither single-dose nor prolonged administration of NAC prevented the hemodynamic changes following administration of DTZ or IOH, respectively. Acute prophylactic administration of NAC prevented increased urinary ET excretion after injection of IOH and, to a smaller degree, of DTZ. Both an ionic, high-osmolar (DTZ) and a nonionic, low-osmolar (IOH) radiocontrast agent induce marked changes in renal hemodynamics in salt-depleted rats treated with indomethacin. CONCLUSIONS: Renal perfusion is not affected by NAC application in a model of experimental contrast nephropathy in rats. Other effects of NAC might thus account for the presumed renoprotective properties.

Comparison of early renal function parameters for the prediction of 5-year graft survival after kidney transplantation.

BACKGROUND: Early graft function (EGF) has an enduring effect on the subsequent course after kidney transplantation. This study compares quantitative parameters of EGF for the prediction of graft survival. METHODS: We involved 300 consecutive transplant recipients from deceased donors from 1989 to 2005. Urine output during 24 h post-transplant (UO), and serum creatinine after 1 week (Cr7) were taken for explanatory variables. We generated Kaplan-Meier (K-M) estimates of graft survival, by quintiles of the explanatory variable. Cox regression was applied to control for various recipient factors. RESULTS: K-M survival estimates indicate a threshold effect of UO and Cr7, which can dissect the risk of graft failure. The thresholds referring to the 2nd quintile correspond to a UO >630 ml and a Cr7 <2.5 mg/dl and were associated with a proportional hazard ratio of 0.52 (95% CI 0.33-0.84) and 0.34 (95% CI 0.18-0.65), respectively. Combining both of the parameters predicted a 5-year graft survival probability >90%, according to a hazard ratio of 0.21 (95% CI 0.09-0.46). Requirement of dialysis post-transplant lost its discriminatory power and was not a significant explanatory variable in the multivariate analysis. CONCLUSION: Routine parameters for monitoring of EGF display a threshold effect allowing accurate prediction of 5-year graft survival at the earliest point in time. The quantitative threshold levels for an optimum discriminatory power require validation in a larger, preferably multicentre database.

Treatment of proteinuria with low-molecular-weight heparin after renal transplantation.

The development of nephrotic-range proteinuria after renal transplantation is an unfavourable prognostic factor for graft survival. In contrast to that in other nephropathies, the role of renin-angiotensin blockade in kidney transplantation is less well defined, and its anti-proteinuric effect is markedly reduced in the presence of segmental glomerulosclerosis. Here, we describe two patients who developed severe proteinuria after renal transplantation, despite effective blood pressure control with an ACE inhibitor. Histological changes were consistent with IgA-nephropathy and focal segmental glomerulosclerosis. Both patients were treated with low-molecular-weight heparin in addition to pre-existing ACE inhibition. This regimen led to a significant and long-lasting reduction of proteinuria. Our data suggest that low-molecular-weight heparin possesses strong renoprotective properties, thus confirming previous data from experimental nephropathies. This approach might represent a promising new strategy for treatment of proteinuria after kidney transplantation.

Acetylcysteine for prevention of contrast nephropathy: meta-analysis.

BACKGROUND: Contrast nephropathy is associated with increased in-hospital morbidity and mortality and leads to extension of hospital stay in patients with chronic renal insufficiency. Acetylcysteine seems to be a safe and inexpensive way to reduce contrast nephropathy. We aimed to assess the efficacy of acetylcysteine to prevent contrast nephropathy after administration of radiocontrast media in patients with chronic renal insufficiency. METHODS: We did a meta-analysis of randomised controlled trials comparing acetylcysteine and hydration with hydration alone for preventing contrast nephropathy in patients with chronic renal insufficiency. The trials were identified through a combined search of the BIOSIS+/RRM, MEDLINE, Web of Science, Current Contents Medizin, and The Cochrane Library Databases. We used incidence of contrast nephropathy 48 h after administration of radiocontrast media as an outcome measure. FINDINGS: Seven trials including 805 patients were eligible according to our inclusion criteria and were analysed. Overall incidence of contrast nephropathy varied between 8% and 28%. Since significant heterogeneity was indicated by the Q statistics (p=0.016) we used a random-effects model to combine the data. Compared with periprocedural hydration alone, administration of acetylcysteine and hydration significantly reduced the relative risk of contrast nephropathy by 56% (0.435 [95% CI 0.215-0.879], p=0.02) in patients with chronic renal insufficiency. Meta-regression revealed no significant relation between the relative risk of contrast nephropathy and the volume of radiocontrast media administered or the degree of chronic renal insufficiency before the procedure. INTERPRETATION: Compared with periprocedural hydration alone, acetylcysteine with hydration significantly reduces the risk of contrast nephropathy in patients with chronic renal insufficiency. The relative risk of contrast nephropathy was not related to the amount of radiocontrast media given or to the degree of chronic renal insufficiency before the procedure.