Increased thrombin generation in patients with chronic renal failure

The plasma concentration of prothrombin fragment 1+2 (F1+2) is considered a very sensitive parameter for specific detection of latent hypercoagulability. To evaluate the degree of hypercoagulation associated with chronic uremia, we measured F1+2 by ELISA in the plasma of 51 patients with severe or end-stage chronic renal failure (35 males, 16 females, aged 22–81 years): 24 on dietary treatment, 15 on combined dietary and once a week hemodialysis, and 12 on regular maintenance hemodialysis; 33 healthy subjects served as a control group. Plasma F1+2 showed a significant elevation in the group on dietary treatment; it was further increased in the group on once a week hemodialysis, and even more markedly increased in the group on maintenance hemodialysis. In patients on dietary treatment a positive correlation was found between plasma F1+2 and serum creatinine. In patients on maintenance hemodialysis, no increase in the F1+2 plasma level was found during the course of a single hemodialysis session. Low molecular weight heparin, administered to 7 patients on dietary treatment, caused a marked drop in the F1+2 plasma level, providing evidence that the elevation in F1+2 indicates an accelerated in vivo thrombin generation rather than impaired renal catabolism. The enhanced coagulation activation appears to be related to the reduction of residual renal function, i.e., to the severity of renal failure, and may contribute to the increased risk of vascular events in uremic patients.     

Effects of a low-phosphorus, low-nitrogen diet supplemented with essential amino acids and ketoanalogues on serum beta-endorphin in chronic renal failure

The effects of a vegetarian low-protein, low-phosphorus diet supplemented with essential amino acids and ketoanalogues, on the serum beta-endorphin, growth hormone, parathyroid hormone, thyroid hormones (T3 and T4), pituitary TSH and total cortisol were studied in 12 male chronic uremics. beta-Endorphin decreased, as well as growth hormone. Parathyroid hormone and T3 improved significantly, reaching almost normal values. It is hypothesized that the correction of the beta-endorphin excess may account in part for the improvement of some endocrinological and metabolic effects exerted by this dietary treatment. The possible pathophysiological mechanisms which could explain the antiendorphinic action of this treatment in uremic patients are discussed, as well as the possible beneficial endocrine and metabolic effects exerted by the fall in circulating beta-endorphin.     

Potential benefits of renal diets on cardiovascular risk factors in chronic kidney disease patients

Dietary manipulation, including protein, phosphorus, and sodium restriction, when coupled with the vegetarian nature of the renal diet and ketoacid supplementation can potentially exert a cardiovascular protective effect in chronic renal failure patients by acting on both traditional and nontraditional cardiovascular risk factors. Blood pressure control may be favored by the reduction of sodium intake and by the vegetarian nature of the diet, which is very important also for lowering serum cholesterol and improving plasma lipid profile. The low protein and phosphorus intake has a crucial role for reducing proteinuria and preventing and reversing hyperphosphatemia and secondary hyperparathyroidism, which are major causes of the vascular calcifications, cardiac damage, and mortality risk of uremic patients. The reduction of nitrogenous waste products and lowering of serum PTH levels may also help ameliorate insulin sensitivity and metabolic control in diabetic patients, as well as increase the responsiveness to erythropoietin therapy, thus allowing greater control of anemia. Protein-restricted diets may have also anti-inflammatory and anti-oxidant properties. Thus, putting aside the still debatable effects on the progression of renal disease and the more admitted effects on uremic signs and symptoms, it is possible that a proper nutritional treatment early in the course of renal disease may be useful also to reduce the cardiovascular risk in the renal patient. However, conclusive data cannot yet be drawn because quality studies are lacking in this field; future studies should be planned to assess the effect of renal diets on hard outcomes, as cardiovascular events or mortality.     

Effects of oral administration of heparan sulphate in the rat remnant kidney model

Heparins are useful for the protection of residual renal function in several nephropathies, but the anticoagulant action and the need of parenteral administration are two main drawbacks limiting their use in chronic renal failure patients. Heparan sulphate (HS) is a heparin-like mucopolysaccharide devoid of anticoagulant action and active orally. In this study, the effects of HS oral administration have been evaluated in 18 subtotally nephrectomized rats;18 untreated remnant kidney rats served as control. No mortality was observed in the HS-treated rats, whereas in the control rats the survival rate was 72.2% at 18 weeks. At the end of the study, HS-treated rats showed lower urinary protein excretion (44 +/- 22 vs. 80 +/- 54 mg/24 h, p < 0.01), lower urea plasma levels (75 +/- 34 vs. 134 +/- 105 mg/dl, p < 0.01) and higher creatinine clearance (66 +/- 15 vs. 47 +/- 21 ml/min. 10(2), p < 0.05) than control rats. Remnant kidney weight (2.3 +/- 1.1 vs. 1.3 +/- 0.2 g, p < 0.01) and heart weight (1.3 +/- 0.2 vs. 1.1 +/- 0.1 g, p < 0.05) were greater in the control than in the HS-treated rats, as well as the systemic blood pressure values (167 +/- 19 vs. 115 +/- 32 mm Hg, respectively, p < 0.001). The remnant kidney histological examination in the HS-treated rats showed a lower prevalence of glomerular sclerosis, mesangial proliferation, and a much less evident tubulointerstitial damage than in controls. The antiproliferative and anti-inflammatory actions of HS together with its protective action on the endothelium are the putative mechanisms that could account for our findings. In conclusion, the present study supports evidence of an antiproteinuric and a renoprotective effect of orally administered HS in subtotally nephrectomized rats. This is in keeping with the well-known effects exerted also by other heparins, but the effectiveness of an orally available heparin-like product in this animal model could suggest the possibility of a clinical use also in progressing chronic renal failure patients.     

Update on ovarian hyperstimulation syndrome: part 2--clinical signs and treatment

Patients with polycystic ovary syndrome (PCOS), hyperandrogenemia and hypothalamic ovarian dysfunction have a predisposition for developing ovarian hyperstimulation syndrome (OHSS). Choosing treatment protocols carefully, cautious stimulation, minimizing hCG dosages for ovulation induction, and refraining from embryo transfer in case of doubt, can markedly reduce the risk. In the treatment of moderate and severe hyperstimulation syndrome, adequate hydration with fluid balance, prophylaxis against thrombosis, ascites drainage when appropriate, and close monitoring and intensive-care monitoring if necessary, must be ensured. The aim of procedures in reproductive-medicine should be to achieve pregnancy rates that are as high as possible with as few side effects of the treatment as possible.     

Blood group A: an overseen risk factor for early-onset ovarian hyperstimulation syndrome?

Ovarian hyperstimulation syndrome (OHSS), a potentially life-threatening complication, is classified into two distinct forms, early-onset and late-onset OHSS. Few risk factors have been established, but no association with ABO blood group antigens was known. From January 2000 to October 2007, 122 patients with known blood groups and the diagnosis of OHSS were hospitalized. OHSS classification, pregnancies, age and time of in-patient treatment were collated. Two control groups were established. One group comprised 177 patients treated for infertility without developing OHSS (treatment/no OHSS) and known blood groups. A second one consisted of 2289 obstetric and gynaecological patients (O/G). OHSS grade I, II or III was found in 20, 47 and 55 patients, respectively. The pregnancy rate was 50.8% and did not differ among the different OHSS grades. Blood group A was significantly more frequent and blood group O less frequent in patients with early-onset OHSS compared with the two control cohorts (P = 0.009 versus treatment/no OHSS; P = 0.001 versus O/G). The odds ratio for patients with blood group A versus O to develop early-onset OHSS was 2.169 and 2.262, respectively. No increased risk for late-onset OHSS was found. Blood group A may be associated with early-onset OHSS in Caucasians.