Improved cognitive function after kidney transplantation compared to hemodialysis.

End-stage renal disease is associated with chronic stress that in turn may result in endocrine changes, affect cognitive, and physical capacities and increase the risk for cardiovascular events. The objective of this study was to evaluate and characterize possible stress parameters and compare cognitive function in those patients. Physiological and biochemical stress parameters as well as cognitive function were assessed in 17 hemodialysis and 18 renal transplant patients and both groups were compared. Serum cortisol and interleukin-6 levels were elevated in both groups but showed no significant difference. Cholesterol and low-density lipoprotein levels were significantly higher in patients following renal transplantation. While heart rate variability was comparable in both groups, most cognitive tests showed better results in renal transplant patients. We showed that: (1) cognitive function may improve following renal transplantation; (2) standard biochemical stress parameters are not useful to discriminate stress in patients with chronic kidney disease; and (3) heart rate variability is unaltered in this setting.

Functional Assessment of Fatigue and Other Patient-Reported Outcomes in Patients Enrolled in the Global aHUS Registry.

INTRODUCTION: Atypical hemolytic uremic syndrome (aHUS) is a progressive and potentially life-threatening disease characterized by complement-mediated thrombotic microangiopathy. Patients with aHUS may experience fatigue, which can negatively impact their lives, but there is a knowledge gap regarding disease burden in these patients. METHODS: In this longitudinal study, patients with aHUS from the Global aHUS Registry who completed patient-reported outcome assessments (Functional Assessment of Chronic Illness Therapy-Fatigue scale [FACIT-Fatigue], general health status, and work status) at ≥2 time points were assessed relative to treatment status: (i) never treated with eculizumab; (ii) on eculizumab at registry enrollment and continued therapy; and (iii) started eculizumab after registry enrollment. RESULTS: Patients who started eculizumab after the baseline visit (n = 23) exhibited improvements in fatigue (nearly 75% achieved clinically meaningful improvement), improved general health status (55%), and 25% to 30% rate reduction in symptoms of fatigue, weakness, irritability, nausea/vomiting, and swelling at last follow-up. Among patients already on eculizumab at registry enrollment (n = 295) and those never treated (n = 233), these parameters changed minimally relative to the baseline. Emergency room visits and hospital admissions were similar between groups. The number of health care provider visits and work days missed were higher in patients who started eculizumab after registry enrollment. CONCLUSION: These real-world findings confirm the detrimental effects of aHUS on patients' daily lives, including high levels of fatigue and impairments in general health status. The results suggest clinically meaningful improvement in fatigue, other patient-reported outcomes, and symptoms with eculizumab initiation after enrollment into the aHUS registry.

Self-management in adrenal insufficiency - towards a better understanding.

Patients with adrenal insufficiency (AI) require life-long glucocorticoid (GC) replacement treatment and dose adjustment in stress situations to prevent life-threatening adrenal crises. Herein this study we evaluated the patients' healthcare situation and their knowledge on AI, comparing various aspects to a prior survey in 209 physicians. Using a questionnaire, we conducted a comprehensive survey among 33 AI patients who were treated at the endocrine outpatient clinics of two University Hospitals in Germany. The majority of AI patients (97%) named their treating physician as main source for information. Overall, 89.7% of interviewees were satisfied with their medical treatment; however, about 1/3 reported controversies with healthcare professionals regarding GC replacement in various situation. Two thirds of AI patients increased their substitution dose temporarily within the last 12 months. However, not all patients had an emergency ID, and only 64.5% an emergency kit. None of the interviewed patients identified the need for adjustment in all given situations correctly. Almost 80% of patients did not correctly identify all symptoms of GC over- and under-replacement. Interestingly, we found no significant differences between patients and physicians regarding specific aspects of GC replacement. We showed that: (i) AI patients have some knowledge gaps on modalities and adequacy of GC replacement therapy; (ii) long-term management of patients with AI remains a challenge requiring an experienced specialist; and (iii) further education of physicians as primary source of information is necessary. Additional education may help AI patients to empower them to adequate self-treatment.

Beating the odds--surviving extreme hyperkalemia.

Severe hyperkalemia (>7 mmol/L) is a medical emergency because of possible fatal arrhythmias. We here report the case of a 58-year-old woman surviving extreme hyperkalemia (>10 mmol/L). The patient with a history of congestive heart failure, a DDD pacemaker and mild chronic renal insufficiency was admitted with progressive weakness and sudden onset of hypotension and bradycardia in the absence of any pacemaker action. Laboratory tests revealed an extreme serum potassium level of 10.1 mmol/L, with a slightly elevated serum creatinine of 149 µmol/L. Treatment with norepinephrine, sodium bicarbonate, and insulin improved both the hemodynamic situation and the serum potassium with subsequent regaining pacemaker actions even before additional hemodialysis normalized the potassium level. A thorough investigation demonstrated that several mechanisms contributed to the extreme potassium level: urinalysis and a low transtubular potassium gradient in the presence of metabolic acidosis with normal anion gap pointed to preexisting interstitial nephritis, with renal tubular acidosis type IV as the predisposing factor, whereas several drugs and acute impairment of renal function contributed to the dangerous situation. Despite the odds for fatal outcome, the patient recovered completely, and long-term management was initiated to prevent recurrent hyperkalemia.

No aggravation of renal injury in apolipoprotein E knockout mice (ApoE(-/-)) after subtotal nephrectomy.

BACKGROUND: There is substantial experimental evidence that various forms of dyslipidaemia aggravate the course of renal failure and that reversal of dyslipidaemia ameliorates progression of renal failure. The apolipoprotein E knockout mouse (ApoE(-/-)) is an established model of accelerated atherogenesis. We investigated whether the course of renal disease after uninephrectomy (UNX) and subtotal nephrectomy (SNX) is altered in ApoE(-/-) mice compared with their genetic controls. METHODS: Ten-week-old, male ApoE(-/-) mice (body weight 25+/-2 g) were subjected either to sham operation (sham), UNX or SNX. C57BL/6 sham, UNX and SNX mice served as controls (body weight 26+/-3 g). The food intake of ApoE(-/-) and C57BL/6 mice was kept identical by a pair-feeding protocol. After 12 weeks, mean arterial blood pressure and heart rate were measured in awake resting mice, the kidneys were perfusion fixed and analysed using quantitative histological methods, immunohistochemistry and RT-PCR. RESULTS: At baseline, the sham ApoE(-/-) mice had significantly higher (P<0.05) serum cholesterol and triglycerides than the controls. In parallel, mean arterial blood pressure was significantly elevated in sham ApoE(-/-) mice compared with controls (137+/-15 vs 116+/-4 mmHg; P<0.05). In the sham groups, the glomerulosclerosis index was significantly higher in the ApoE(-/-) mice (1.05+/-0.14 vs 0.57+/-0.07; P<0.05), whereas the tubulointerstitial damage score was comparable (0.06+/-0.04 vs 0.04+/-0.02; n.s.). After SNX there was a significant increase in glomerulosclerosis index, but no difference could be detected between ApoE(-/-) and controls (1.75+/-0.16 vs 1.61+/-0.01, n.s.). The same was true for the tubulointerstitial damage index. CONCLUSIONS: Despite some glomerulosclerosis and elevated mean arterial blood pressure at baseline, no acceleration of progression of renal disease was found in this genetic model of hyperlipoproteinaemia. This observation suggests that despite the known spontaneous histological changes in untouched kidneys, however, the presence of hyperlipidaemia in the ApoE(-/-) mouse does not cause more severe progression in the present models of moderate renal disease.

Cardiomyocyte loss in experimental renal failure: prevention by ramipril.

BACKGROUND: The development of left ventricular hypertrophy (LVH) and of structural abnormalities of the heart is a key abnormality in renal failure that potentially contributes to the high rate of cardiac death. In renal failure, the behavior of cardiomyocyte volume and number in the development of LVH has so far not been investigated. A potential role of the (local) renin-angiotensin system (RAS) in the genesis of LVH has been suspected. It was the aim of the present study in short-term experimental renal failure (1) to characterize cardiomyocyte volume and number and (2) to study whether they are affected by the angiotensin-converting enzyme (ACE) inhibitor ramipril. METHODS: Sprague-Dawley rats (N = 8 to 10 per group) had a subtotal nephrectomy (SNX) or sham operation and followed for 8 weeks. One SNX group received the ACE inhibitor ramipril (0.5 mg/kg body weight) in the drinking fluid. After perfusion fixation, the morphology of the heart was investigated using stereologic techniques. RESULTS: Systolic blood pressure was slightly, but not significantly, higher in untreated SNX, but the left ventricular (LV) weight and LV weight/body weight ratio (2.32 +/- 0.20 mg/g) were significantly higher in SNX than in sham-operated animals (1.90 +/- 0.16 mg/g). Sarcomeric length was not significantly different between SNX and sham-operated animals. There was an increase in the number of terminal deoxynucleotidyl transferase-mediated uridine triphosphate nick end labeling (TUNEL)-positive myocytes in SNX compared to sham-operated animals and a significant increase in cardiomyocyte volume (15,713 +/- 4557 microm3 vs. 10,067 +/- 2242 microm3, P < 0.01) as well as a decrease of cardiomyocyte numbers per unit myocardial volume (61.2 +/- 16.2 vs. 92.2 +/- 20.9 x 103/mm3) and per left ventricle (70.9 +/- 16.5 x 106 vs. 94.8 +/- 18.1 x 106, P < 0.05). Both abnormalities were abrogated by treatment with ramipril (6347 +/- 972.4 microm3 and 106 +/- 18.9 103/mm3 or 118 +/- 39.5 x 106, respectively), which also completely prevented the increase in LV weight/body weight ratio (1.83 +/- 0.14 mg/g). CONCLUSION: LVH in renal failure is characterized by cardiomyocyte hypertrophy, but also cardiomyocyte drop out. A role of the RAS is suggested by the beneficial effect of ramipril treatment that is not accounted for by differences in blood pressure.