Patients with moderate CKD under specialist care have a high disease burden. Improved diagnostic accuracy, rigorous management of risk factors and unravelling of the genetic predisposition may represent strategies for improving prognosis.
The GCKD study will establish one of the largest cohorts to date of CKD patients not requiring renal replacement therapy. Similarities in its design with other observational CKD studies, including cohorts that have already been established in the USA and Japan, will allow comparative and joint analyses to identify important ethnic and geographic differences and to enhance opportunities for identification of relevant risk factors and markers.
Self-reported gout is common among patients with CKD and lower GFR is strongly associated with gout. Pharmacological management of gout in patients with CKD is suboptimal. Prospective follow-up will show whether gout and hyperuricaemia increase the risk of CKD progression and cardiovascular events in the GCKD study.
IntroductionSepsis is still a leading cause of morbidity and mortality, even in modern times, and thrombocytopenia has been closely associated with unfavorable disease outcome. Decreases in mitochondrial membrane potential (depolarization) were found in different tissues during sepsis. Previous work suggests that mitochondrial dysfunction of platelets correlates with clinical disease activity in sepsis. However, platelet mitochondrial membrane potential (Mmp) has not been investigated in a clinical follow-up design and not with regard to disease outcome.MethodsIn this study, platelet mitochondrial membrane depolarization was assessed by means of a fluorescent Mmp-Index with flow cytometry in 26 patients with sepsis compared with control patients. Platelet Mmp-Index on admission was correlated with the clinical disease scores Acute Physiology and Chronic Health Evaluation Score II (APACHE II), Sequential Organ Failure Score (SOFA), and Simplified Acute Physiology Score II (SAPS II). Finally, platelet Mmp-Index on admission and follow-up were compared in the group of sepsis survivors and nonsurvivors. Expression of the prosurvival protein Bcl-xL in platelets was quantified by immunoblotting.ResultsPlatelet mitochondrial membrane depolarization correlated significantly with the simultaneously assessed clinical disease severity by APACHE II (r = -0.867; P < 0.0001), SOFA (r = -0.857; P <0.0001), and SAPS II score (r = -0.839; P < 0.0001). Patients with severe sepsis showed a significant reduction in platelet Mmp-Index compared with sepsis without organ failure (0.18 (0.12 to 0.25) versus 0.79 (0.49 to 0.85), P < 0.0006) or with the control group (0.18 (0.12 to 0.25) versus 0.89 (0.68 to 1.00), P < 0.0001). Platelet Mmp-Index remained persistently low in sepsis nonsurvivors (0.269 (0.230 to 0.305)), whereas we observed recovery of platelet Mmp-Index in the survivor group (0.9 (0.713 to 1.017)). Furthermore, the level of prosurvival protein Bcl-xL decreased in platelets during severe sepsis.ConclusionIn this study, we demonstrated that mitochondrial membrane depolarization in platelets correlates with clinical disease severity in patients with sepsis during the disease course and may be a valuable adjunct parameter to aid in the assessment of disease severity, risk stratification, and clinical outcome.
Patients with peripheral arterial disease (PAD) may develop a broad range of peripheral nerve dysfunctions including pain and sensory deficiencies due to chronic ischemia mostly involving the lower limbs. To investigate the degree of sensory abnormalities in such patients quantitative sensory testing (QST) might be a useful tool. Forty-five patients and 20 controls were enrolled in the present study and underwent QST according to the protocol of the German Research Network on Neuropathic Pain. PAD was graded according to the Rutherford classification. PAD patients were divided into two groups: 16 patients with critical limb ischemia (severe PAD) and 29 patients with intermittent claudication (moderate PAD). QST revealed impaired cold and warm detection, increased mechanical and vibration detection thresholds, and increased perceptual wind-up on the affected leg (all p<0.001). Paradoxical heat sensation (p<0.05) and dynamic mechanical allodynia (p<0.01) were also observed. Subgroup analysis of patients without diabetes (control n=20, moderate PAD n=21, severe PAD n=8) confirmed most of these findings. In patients with severe PAD, sensory deficits were more pronounced than in patients with moderate PAD and were detected even in the face. These data indicate that QST can detect sensory abnormalities in PAD patients. While the pattern of decreased perception suggests deafferentation for Abeta-, Adelta-, and C-fiber inputs, the presence of allodynia suggests that central sensitization also plays a role in the pain state of PAD patients. Subgroup analysis points towards a PAD-associated peripheral neuropathy independent of diabetes.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.