Minoxidil for Treatment of Resistant Hypertension in Chronic Kidney Disease--A Retrospective Cohort Analysis.

Resistant hypertension is still a challenge and reserve antihypertensive agents are often necessary to achieve blood pressure control. One reserve antihypertensive is minoxidil, a direct vasodilator that is known for its strong blood pressure-lowering effect, but contemporary studies are sparse. The authors retrospectively analyzed 54 inpatients with uncontrolled hypertension despite the combined use of current antihypertensive agents. To investigate the effect of minoxidil when added to other antihypertensive agents, blood pressure was evaluated at the time minoxidil treatment was initiated and at discharge. Minoxidil treatment was associated with a significant reduction in blood pressure from 162.4±15.1/83.2±12.7 mm Hg to 135.8±12.2/72.8±6.9 mm Hg (P<.0001). This effect was sustained across all analyzed subgroups. Although the well-known adverse events of minoxidil limit its widespread use, these data show that minoxidil as a reserve antihypertensive agent still has a niche indication in the particular subgroup of patients with treatment-resistant or uncontrolled hypertension.

Performance of the 1 mg dexamethasone suppression test in patients with severe obesity.

OBJECTIVE: To analyze the performance of the 1 mg dexamethasone suppression test (DST) in patients with obesity. Special attention was paid to the influence of interfering medication on DST. METHODS: In this prospective cohort study (Mannheim Obesity Study), patients with obesity were evaluated before bariatric surgery. For evaluation of hypercortisolism, a 1 mg dexamethasone-suppression test (DST) in all subjects was performed. Medication was assessed for possible interference. RESULTS: Two hundred seventy-eight patients with a mean age of 42.3 years (68.8% women) and a mean BMI of 47.9 ± 8.4 kg/m(2) were screened. Insufficient suppression of cortisol after DST was found in 24 patients (8.6%). In two patients hypercortisolism was confirmed. The specificity for DST was calculated at 92.0%. Only CYP3A4 inducers (n = 22, 7.9%) and estrogen therapy (n = 17, 6.1%) were significantly associated with falsely elevated cortisol after DST. Regression analysis excluded any interrelation between DST and anthropometry. CONCLUSIONS: Low prevalence of hypercortisolism (0.7 or <1.8%) was found. Specificity of DST in this cohort typically screened for hypercortisolism was 92.0% (≤ 50 nmol/L). DST should be avoided in patients taking CYP3A4 inducers or estrogen therapy, due to their significant interaction. In summary, the 1 mg DST is an adequate test for screening for hypercortisolism even in patients with extreme obesity.

Excellent graft and patient survival after renal transplantation from donors after brain death with acute kidney injury: a case-control study.

BACKGROUND: Whether organs from donors after brain death (DBD) with acute kidney injury (AKI) should be accepted for transplantation is still a matter of debate. METHODS: This was a retrospective, center-based, matched cohort study of 33 renal transplant patients who received a renal allograft from a DBD with AKI. Sixty-five kidney transplants without donor AKI transplanted directly before and after the index transplantation served as controls. RESULTS: All AKI donors were classified according to RIFLE criteria: 9.1 % Risk, 54.6 % Injury, and 36.4 % Failure. Mean serum creatinine was 2.41 ± 0.88 mg/dL at procurement and 1.06 ± 0.32 mg/dL on admission. AKI donors had lower 24-h urine production (3.22 ± 1.95 vs. 4.59 ± 2.53 L, p = 0.009) and received more frequently noradrenaline (93.9 vs. 72.3 %, p = 0.02) and/or adrenaline (15.2 vs. 1.5 %, p = 0.02). Recipient and transplant characteristics were similar except a more favorable HLA match in control patients (p = 0.01). Hemodialysis posttransplant was more frequently used in AKI recipients (14/33 [42.4 %] vs. 18/65 [27.7 %], p = 0.17). While significant elevations in serum creatinine were noted in these patients until 10 days after transplantation, this difference lost statistical significance by day 14. One-year graft survival was very similar when comparing the groups (93.6 % [95 % CI 76.8-98.4 %] vs. 90.3 % [95 % CI 79.6-95.5 %], log rank p = 0.58). CONCLUSIONS: Kidneys from AKI donors can be transplanted with excellent intermediate prognosis and should not be discarded.

Central vein stenosis in a dialysis patient: a case report.

INTRODUCTION: Central vein stenosis is not a rare problem in patients on dialysis. Placement of a central vein catheter for dialysis access substantially increases the risk of central vein stenosis. However, even in patients without a previous history of central vein catheter placement, a stenosis can be found in up to 40% of patients. CASE PRESENTATION: We report the case of a 60-year-old male Caucasian German dialysis patient who complained of dry cough, swelling of his right arm and facial edema. Computed tomography venography showed a near-total stenosis of his brachiocephalic vein. We discuss the incidence and risk of central vein stenosis in patients on dialysis and report on a successful minimally invasive interventional treatment. CONCLUSION: Central vein stenosis is not a rare problem in patients on hemodialysis and can even occur without previous placement of central venous catheters. High shunt volumes seem to increase the risk associated with central vein catheters.

Aneurysmal subarachnoid hemorrhage (aSAH) results in low prevalence of neuro-endocrine dysfunction and NOT deficiency.

Neuro-endocrine deficiencies have been argued to be common sequelae after aneurysmal subarachnoid hemorrhage (aSAH). As this, however, does not resemble our clinical experience, we studied the incidence of neuro-endocrine and neuropsychological deficits after aSAH. Twenty-six patients (20 females) were prospectively screened for neuro-endocrine and neuropsychological deficits 3, 6 and 12 months after aSAH. GH, IGF-1, prolactin, LH, FSH, estradiol, testosterone, ACTH as well as cortisol during ACTH-stimulation were assessed. Neuropsychological analysis covered verbal comprehension, short term and working memory, visuospatial construction, figural memory, psychomotor speed, attention, and concentration. During the study period 5 individuals demonstrated neuro-endocrine dysfunction. Hypogonadotrophic hypogonadism resolved spontaneously in 2 patients and central hypothyroidism in one of these patients during the study. After 12 months three patients presented low IGF-1 levels. 73.9% of our cohort was affected by neuropsychological deficits during follow-up. At 3, 6 and 12 months the prevalences were 56.5, 52.6 and 42.1%, respectively. Interestingly, all patients with neuro-endocrine dysfunction presented impaired clinical outcome with a GOS 4 at some time point of the study (GOS 4 vs. 5, 45.5% vs. 0, P = 0.007). We found a low prevalence of neuro-endocrine and a high prevalence of neuropsychological deficits in patients 3, 6 and 12 months after aSAH without significant interrelation. Spontaneous recovery of neuro-endocrine alterations most likely presents an adaption to or dysfunction after severe illness. This hypothesis is strengthened by the fact that only patients with inferior clinical outcome after aSAH as assessed by GOS demonstrated neuro-endocrine dysfunction.

Donor desmopressin is associated with superior graft survival after kidney transplantation.

BACKGROUND: A recent randomized trial showed that pretreatment of the brain-dead donor with low-dose dopamine improves immediate kidney graft function, by limiting injury from cold storage (ClinicalTrials.gov Identifier: NCT00115115). This study determines whether donor exposure to desmopressin (1-deamino-8-d-arginine-vasopressin [DDAVP]) before organ retrieval affects renal transplant outcome. METHODS: This retrospective multicenter cohort study, nested in the database of the dopamine trial, includes 264 deceased heart-beating donors with confirmed brain death and corresponding 487 renal allograft recipients transplanted at 60 European centers between March 2004 and August 2007. We assessed differences in delayed graft function, biopsy-proven acute rejections, and 2-year kidney graft survival in recipients of a DDAVP-exposed versus unexposed graft. RESULTS: DDAVP was associated with improved graft survival (85.4% vs. 73.6%, P=0.003). This survival benefit persisted after censoring for death with functioning graft (91.1% vs. 82.0%, P=0.01) and after adjustment for confounders including covariate adjustment from propensity scoring (hazard ratio 0.40, 95% confidence interval [CI] 0.21-0.77; P=0.006). Delayed graft function (odds ratio 0.97, 95% CI 0.57-1.65; P=0.92) and biopsy-proven acute rejections (odds ratio 1.32, 95% CI 0.70-2.49; P=0.40) were unaffected. The survival effect was enhanced after a shorter cold ischemic time less than 14 hr (91.3% vs. 77.8%, P=0.008) and after dopamine pretreatment (92.7% vs. 78.6%, P=0.006). By contrast, prolonged cold ischemic time more than or equal to 14 hr (91.2% vs. 86.5%, P=0.39) and assignment to the nondopamine group (89.7% vs. 84.8%, P=0.37) abrogated the survival advantage. CONCLUSIONS: Donor DDAVP seems to improve renal allograft survival. Combined use of donor DDAVP and low-dose dopamine should receive further evaluation.

Effects of donor pre-treatment with dopamine on survival after heart transplantation: a cohort study of heart transplant recipients nested in a randomized controlled multicenter trial.

OBJECTIVES: We determined the outcome of cardiac allografts from multiorgan donors enrolled in a randomized trial of donor pre-treatment with dopamine. BACKGROUND: Treatment of the brain-dead donor with low-dose dopamine improves immediate graft function after kidney transplantation. METHODS: A cohort study of 93 heart transplants from 21 European centers was undertaken between March 2004 and August 2007. We assessed post-transplant left ventricular function (LVF), requirement of a left ventricular assist device (LVAD) or biventricular assist device (BVAD), need for hemofiltration, acute rejection, and survival of recipients of a dopamine-treated versus untreated graft. RESULTS: Donor dopamine was associated with improved survival 3 years after transplantation (87.0% vs. 67.8%, p = 0.03). Fewer recipients of a pre-treated graft required hemofiltration after transplant (21.7% vs. 40.4%, p = 0.05). Impaired LVF (15.2% vs. 21.3%, p = 0.59), requirement of a LVAD (4.4% vs. 10.6%, p = 0.44), and biopsy-proven acute rejection (19.6% vs. 14.9%, p = 0.59) were not statistically different between groups. Post-transplant impaired LVF (hazard ratio [HR]: 4.95; 95% confidence interval [CI]: 2.08 to 11.79; p < 0.001), requirement of LVAD (HR: 6.65; 95% CI: 2.40 to 18.45; p < 0.001), and hemofiltration (HR: 2.83; 95% CI: 1.20 to 6.69; p = 0.02) were predictive of death. The survival benefit remained (HR: 0.33; 95% CI: 0.12 to 0.89; p = 0.03) after adjustment for various risks affecting mortality, including pre-transplant LVAD/BVAD, inotropic support, and impaired kidney function. CONCLUSIONS: Treatment of brain-dead donors with dopamine of 4 µg/kg/min will not harm cardiac allografts but appears to improve the clinical course of the heart allograft recipient. (Prospective Randomized Trial to Evaluate the Efficacy of Donor Preconditioning With Dopamine on Initial Graft Function After Kidney Transplantation; NCT00115115).

Impact of food and herbal medication on calcineurin inhibitor dose in renal transplant patients: a cross-sectional study.

The incidence and severity of interactions of herbal products with calcineurin inhibitor (CNI) metabolism in renal transplant recipients have not been systematically investigated. These patients have a high rate of herbal product consumption, including products interfering with CNI metabolism. The study aimed at identifying an impact of herbs and foods on CNI metabolism in a cohort of renal transplant recipients by conducting dietary interviews (1) in patients with very low and high CNI maintenance dose requirements and (2) by retrospective analysis of unexplained marked deviations from CNI baseline trough levels. Of 73 renal transplant recipients, 59 were treated with a CNI-based immunosuppressive regimen. Seven patients with an exceptionally high or low CNI dose were interviewed. Five of these seven patients had not consumed any plant product with known influence on CNI metabolism. In one patient chicory-coffee and bitter chocolate had been suspected as contributing to high CNI dose requirement, but the dose could not be lowered after discontinuation of these foods. Participating nephrologists reported three as yet unexplained temporary deviations from baseline CNI trough levels, of which two could be linked to newly started consumption of high volumes of herbal teas and the other to St. John's wort. Consumption of herbal products within the study cohort had no detectable impact on maintenance doses of CNI. However, herbal products, and specifically teas when consumed by the liter, could be linked to temporary strong deviations from CNI trough levels. The study demonstrates that as yet unnoticed herbal interactions with CNI can be detected by detailed dietary analysis, but that the overall impact on maintenance doses of CNI appears to be low.

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.

Use of highly sensitive C-reactive protein for followup of Wegener's granulomatosis.

OBJECTIVE: Since Wegener's granulomatosis (WG) represents a relapsing disease, efforts have been made to reliably predict relapses using blood tests. Followup measures such as conventionally determined C-reactive protein (CRP), antineutrophil cytoplasmic antibody (C-ANCA) titer, and proteinase-3 (PR3) ELISA are applied. We evaluated whether during remission elevated highly sensitive CRP (hsCRP) precedes relapse as a marker of subclinical inflammation and thus might improve clinical assessment. METHODS: We investigated 227 sera of 57 patients with WG: 74 sera collected from patients in remission who subsequently relapsed (before relapse), 30 sera collected during relapse, and 123 sera from patients in remission without relapse. We also distinguished between major and minor relapse. hsCRP, conventionally determined CRP (CRP), C-ANCA, PR3-ELISA, and erythrocyte sedimentation rate (ESR) were measured using commercial kits, and levels were correlated to clinical status. RESULTS: Only hsCRP and ANCA titer, but not CRP levels, were higher in sera from patients who subsequently relapsed versus those who did not, indicating patients at risk. Levels of hsCRP, CRP, and ESR were higher in sera collected during relapse than in the sera before relapse. hsCRP, conventional CRP, and ESR were also higher in samples collected during major relapse than before major relapse. Looking at the levels just before relapse compared to previous levels during remission, none of these measures rose directly before the clinical manifestation of the relapse. CONCLUSION: Our study provides evidence for an additional value of hsCRP in the clinical assessment of patients with WG.

Effects of a clinical pathway on quality of care in kidney transplantation: a non-randomized clinical trial.

PURPOSE: Standardization of care is essential for improving outcome of kidney transplantation (KT). Clinical pathways (CPs) are known to standardize and improve perioperative care for a number of interventions. In transplantation medicine, however, pertinent evidence is very limited. This study evaluates effects of a CP on quality of care in KT. MATERIALS AND METHODS: Consecutive patients (n=32) undergoing KT between July 2006 and August 2007 who were treated with a CP were compared to patients (n=44) treated without CP between January 2005 and June 2006. Several quality indicators regarding process and outcome were compared between groups. RESULTS: Quality of care was significantly higher in the CP group for the following indicators: timely removal of central venous catheters, wound drains, and Foley catheters and control of cyclosporine levels, respiratory exercising, and pain control. Median stay decreased non-significantly from 21.4 to 18.3 days. There was significantly less delayed graft function in the CP group. All other outcome indicators showed no significant differences. CONCLUSIONS: Implementation of a CP for KT improves the quality of perioperative treatment by standardizing care. Regarding effects on outcome, no clear conclusion can be drawn. We recommend that large randomized studies are conducted to evaluate the latter issue.

Retinoid X receptor beta polymorphisms do not explain functional differences in vitamins D and A response in Antineutrophil cytoplasmic antibody associated vasculitis patients.

It has been suggested that the retinoid X receptor beta (RXRB) gene is a risk factor for Wegener's granulomatosis. We addressed if there is a functional difference in the response to retinoic acid (RA) and vitamin D in Antineutrophil cytoplasmic antibody (ANCA) associated systemic vasculitis (AASV) patients and if this was associated with RXRB genotypes. TNFalpha and IL-10 production were measured in whole blood assay from AASV patients (n = 51) and healthy controls (HC, n = 67). One micromolar of 1,25-(OH)(2) D3, 9-cis RA (9c-RA) or all-trans RA (ATRA) was added to the assay. Genotyping was performed for exons 7 and 2 of the RXRB gene and for a microsatellite in vicinity of the RXRB gene. Lipopolysaccharide (LPS) mediated TNFalpha production and IL-10 were significantly lower in patients. Addition of 1,25-(OH)(2) D3, ATRA or 9c-RA, blunted TNFalpha production, more pronounced in patients. Although all three compounds inhibited IL-10 production significantly in HC, only 1,25-(OH)(2) D3 was found to be effective in patients. Allele distribution of the RXRB microsatellite differed significantly between patients and HC. This was not found for the SNP in exons 2 and 7. Genotype of the latter correlated with the ability of 1,25-(OH)(2) D3 and ATRA to inhibit IL-10 production. We provide immunological evidence for a functional difference in vitamins D and A responsiveness in AASV patients. Since the inhibition of TNFalpha was more effective in patients, vitamin D supplementation might be an additional therapeutical approach.

ANCA-associated vasculitis following influenza vaccination: causal association or mere coincidence?

Whether autoimmune or rheumatic disease may be precipitated after vaccination is controversially discussed among experts. Here we describe 4 cases of new onset or relapsing antineutrophil cytoplasmic antibodies associated vasculitis occurring in timely association with influenza vaccination. In the literature different subtypes of vasculitis have been repeatedly reported after influenza vaccination. Several trials in patients with preexisting auto-immune disease failed to indicate an increased risk for disease recurrence after influenza vaccination but these investigations might be underpowered to detect this very rare but relevant side effect. Although our report does not prove a causal association between vaccination and vasculitis, it seems possible that in rare cases vaccination might induce vasculitic disease.

Effects of donor pretreatment with dopamine on graft function after kidney transplantation: a randomized controlled trial.

CONTEXT: Kidney graft function after transplantation can be improved through pharmacological donor pretreatment to limit organ injury from cold preservation. OBJECTIVE: To determine whether pretreatment of brain-dead donors with low-dose dopamine improves early graft function in human renal transplant recipients. DESIGN, SETTING, AND PATIENTS: Randomized, open-label, multicenter, parallel-group trial of 264 deceased heart-beating donors and 487 subsequent renal transplants performed at 60 European centers between March 2004 and August 2007 (final follow-up, December 31, 2008). Eligible donors were stable under low-dose norepinephrine with a normal serum creatinine concentration on admission. INTERVENTIONS: Donors were randomized to receive low-dose dopamine (4 mug/kg/min). MAIN OUTCOME MEASURES: Dialysis requirement during first week after transplantation. RESULTS: Dopamine was infused for a median of 344 minutes (IQR, 215 minutes). Dialysis was significantly reduced in recipients of a dopamine-treated graft. Fewer recipients in the treatment group needed multiple dialyses (56/227; 24.7%; 95% CI, 19.0%-30.3%; vs 92/260; 35.4%; 95% CI, 29.5%-41.2%; P = .01). The need for multiple dialyses posttransplant was associated with allograft failure after 3 years (HR, 3.61; 95% CI, 2.39-5.45; P < .001), whereas a single dialysis was not (HR, 0.67; 95% CI, 0.21-2.18; P = .51). Besides donor dopamine (OR, 0.54; 95% CI, 0.35-0.83; P = .005), cold ischemic time (OR, 1.07; 95% CI, 1.02-1.11 per hour; P = .001), donor age (OR, 1.03; 95% CI, 1.01-1.05 per year; P < .001), and recipient body weight (OR, 1.02; 95% CI, 1.01-1.04 per kg; P = .009) were independent explanatory variables in a multiple logistic regression model. Dopamine resulted in significant but clinically meaningless increases in the donor's systolic blood pressure (3.8 mm Hg; 95% CI, 0.7-6.9 mm Hg; P = .02) and urine production before surgical recovery of the kidneys (29 mL; 95% CI, 7-51 mL; P = .009) but had no influence on outcome. CONCLUSION: Donor pretreatment with low-dose dopamine reduces the need for dialysis after kidney transplantation. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT00115115.

Complementary and alternative medications consumed by renal patients in southern Germany.

BACKGROUND: Complementary and alternative medicine (CAM) is frequently used in the general population, yet scant data are available regarding the prevalence of these medications in patients with end-stage renal disease (ESRD). OBJECTIVE: To survey patients with ESRD regarding their use of CAM and health foods. METHODS: Consecutive patients treated with dialysis or renal transplantation for ESRD were approached by nephrologists of 5 renal centers to report their usage of and knowledge on CAM and health foods by answering a questionnaire. Of 180 approached patients, 164 returned completed questionnaires for analysis. RESULTS: Fifty-seven percent of dialysis patients and 49% of transplant patients reported to be regular CAM-consumers. CAM consumption was positively associated with female sex and negatively with diabetes as comorbidity. Forty-one different CAM products had been named, with mineral supplements and vitamins ranking first. Besides CAM, many renal patients had regularly consumed herbal teas and citrus-juices (50% and 35%, respectively). Close to 40% of the documented CAM/health food consumptions have potential risks for patients because of constituents that either accumulate in renal failure or interact with pharmaceutical medication. However, only about 50% of dialysis patients, but 73% of transplant patients used to inform their physicians about CAM consumption (P = .005). Awareness about interaction risks linked to CAM was especially low in dialysis patients when compared to transplant patients (39% versus 78%, P < .0001) and increased when physicians had routinely questioned patients about their CAM consumption. Currently, however, patients reported that only a minority of physicians had taken an active interest into consumption of these substances. CONCLUSION: Consumption of CAM and health food is common among renal patients. Physicians are currently not adequately informed about CAM consumption by their patients. Because many products are at risk to either accumulate or cause interactions with medication, physicians should take an active role to inform themselves.