Dialysis patients exhibit an inverse, L- or U-shaped association between blood pressure and mortality risk, in contrast to the linear association in the general population. We prospectively studied 9333 hemodialysis patients in France, aiming to analyze associations between predialysis systolic, diastolic, and pulse pressure with all-cause mortality, cardiovascular mortality, and nonfatal cardiovascular endpoints for a median follow-up of 548 days. Blood pressure components were tested against outcomes in time-varying covariate linear and fractional polynomial Cox models. Changes throughout follow-up were analyzed with a joint model including both the time-varying covariate of sequential blood pressure and its slope over time. A U-shaped association of systolic blood pressure was found with all-cause mortality and of both systolic and diastolic blood pressure with cardiovascular mortality. There was an L-shaped association of diastolic blood pressure with all-cause mortality. The lowest hazard ratio of all-cause mortality was observed for a systolic blood pressure of 165 mm Hg, and of cardiovascular mortality for systolic/diastolic pressures of 157/90 mm Hg, substantially higher than currently recommended values for the general population. The 95% lower confidence interval was approximately 135/70 mm Hg. We found no significant correlation for either systolic, diastolic, or pulse pressure with myocardial infarction or nontraumatic amputations, but there were significant positive associations between systolic and pulse pressure with stroke (per 10-mm Hg increase: hazard ratios 1.15, 95% confidence interval 1.07 and 1.23; and 1.20, 1.11 and 1.31, respectively). Thus, whereas high pre-dialysis blood pressure is associated with stroke risk, low pre-dialysis blood pressure may be both harmful and a proxy for comorbid conditions leading to premature death.
FSGS is a renal manifestation of MCs. The renal lesion can precede other manifestations of the genetic disease by many years. The striking arteriolar lesions in these cases may have resulted in glomerular hypertension and hyperperfusion, leading to secondary epithelial cell abnormalities and, ultimately, FSGS. However, primary epithelial cell dysfunction caused by mitochondrial defects could not be ruled out on morphological grounds. MCs should be considered in cases of so-called primary FSGS, particularly if there is a familial history of diabetes, neuromuscular disorders, or deafness.
Periodic systemic capillary leak syndrome (Clarkson disease) is characterized by unexplained attacks of a marked increase in capillary permeability. As leukotrienes, derived from arachidonic acid via the 5-lipoxygenase pathway, enhance capillary permeability, we studied arachidonate metabolism in leucocytes of a patient with capillary leak syndrome. Leucocyte-platelet suspensions, prepared from blood collected from the patient during asymptomatic periods (n = 11) produced greater amounts of 5-hydroxyeicosatetraenoic acid (5-HETE) than control suspensions (P less than 0.05). Peripheral leucocytes, collected during attacks (n = 3) and studied without addition of A23187 released LTB4 in vitro but not sulphidopeptides leukotrienes. This result was never observed with leucocytes from control subjects or from the patient out of a crisis. These results suggest that in the patient, peripheral leucocytes could be stimulated by an unknown, as yet to be determined, endogenous factor to produce more 5-HETE and LTB4. Whether LTB4 plays a pathogenic role in the capillary leakage remains to be determined.
Focal segmental glomerulosclerosis associated with mitochonlar disorders were the first to be studied, and direct evidrial cytopathy. dence of mitochondrial DNA (mtDNA) abnormalities Background. The nonspecific lesion of focal segmental glowas demonstrated as early as 1988 [1, 2]. These clinical merulosclerosis (FSGS) can occur as a primary disease or in manifestations are the consequences of cellular defects a variety of secondary settings. In mitochondrial cytopathies (MCs), the phenotypic expression of the disease depends on in oxidative phosphorylation and adenosine 5Ј-triphosthe degree of cellular dysfunction, and this correlates with the phate (ATP) production by mitochondria, and depend proportion of abnormal mitochondrial DNA in the cells and on the proportion of abnormal mtDNA in the cells and the dependence of tissues on oxidative metabolism. The most the dependence of each tissue on oxidative metabolism. common renal manifestation in MCs is tubular dysfunction; little has been reported about glomerular diseases. Until recently, MCs were considered to be rare; renal Methods. Cases of four adult patients with FSGS and MC are manifestations of MCs were considered to be restricted reported. Routine histology and mitochondrial DNA analysis to childhood. The most common renal clinical presentawere carried out on renal biopsies. Results. Family history and clinical manifestations in the tion of MCs is tubular dysfunction [3]. In adults, progresfour patients with FSGS suggested a diagnosis of MC. An sive renal failure has recently been reported [4], and a A3243G transition in the mitochondrial DNA tRNA leu(UUR) was number of childhood cases of focal segmental glomerulofound in lymphocytes and kidney. Glomerular lesions of FSGS sclerosis (FSGS) have also been reported [5-7]. This were associated with unusual hyaline lesions, which appeared to represent individual myocyte necrosis in afferent arterioles nonspecific glomerular lesion, which accounts for 20% of and small arteries. all nephrotic syndromes in adults, can occur as a primary Conclusion. FSGS is a renal manifestation of MCs. The redisease or in a variety of secondary settings. FSGS apnal lesion can precede other manifestations of the genetic dispears to be the immediate consequence of a primary or ease by many years. The striking arteriolar lesions in these cases may have resulted in glomerular hypertension and hypersecondary visceral glomerular epithelial cell defect or perfusion, leading to secondary epithelial cell abnormalities injury [8-10]. It is associated in many situations with and, ultimately, FSGS. However, primary epithelial cell dysglomerular hypertension and hyperperfusion [11, 12]. function caused by mitochondrial defects could not be ruled We report the association of MC and FSGS in four adults out on morphological grounds. MCs should be considered in cases of so-called primary FSGS, particularly if there is a familand suggest the role of this cellular dysfunction, which ial history of diabetes, neuromuscular disorders, or deafness. is ...
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