S. Alikhani

Hypomagnesemia and renal magnesium wasting in renal transplant recipients receiving cyclosporine

Following the adoption and use of cyclosporine as the drug of choice in the management of renal allograft recipients, several cases of symptomatic hypomagnesemia were noted. These observations prompted the current prospective study of serum concentration and urinary excretion of magnesium in 27 renal transplant recipients treated with cyclosporine and prednisone. Relevant laboratory measurements were obtained shortly before and regularly after transplantation. The results were compared with those obtained in a group of 17 allograft recipients treated with azathioprine and prednisone. The cyclosporine-treated patients showed a significant reduction in the serum magnesium concentration and an inappropriately increased urinary excretion and fractional excretion of magnesium, suggesting renal magnesium wasting. The observed hypomagnesemia required magnesium supplementation in nearly all cyclosporine-treated patients. In contrast, azathioprine-treated patients showed normal serum magnesium concentrations and required no magnesium supplementation. In conclusion, administration of cyclosporine in renal allograft recipients appears to be commonly associated with renal magnesium wasting and hypomagnesemia. Therefore, it is recommended that serum levels of magnesium be monitored regularly in renal allograft recipients receiving cyclosporine and that magnesium supplementation be employed as needed to avoid magnesium depletion.

Coagulation cascade, fibrinolytic system, antithrombin III, protein C and protein S in patients maintained on continuous ambulatory peritoneal dialysis.

We studied the coagulation cascade, fibrinolytic system and naturally occurring anticoagulants in a group of 14 patients with end-stage renal disease maintained on continuous ambulatory peritoneal dialysis (CAPD). The results were compared with those obtained in a group of ten normal volunteers. Plasma procoagulant activities of factors XII, XI, IX, VIII, VII, X and II were significantly greater in the CAPD group as compared to the normal control group. Likewise plasma concentrations of total and free protein S were increased in the CAPD group. Although the mean value for plasma factor V activity in the CAPD group was higher than that found in the control group the difference did not attain statistical significance. In addition plasma fibrinogen concentration and factor VIII-related antigen level were significantly increased in CAPD patients. No significant difference was found between the CAPD patients and the control group with respect to plasma levels of protein C, antithrombin III, plasminogen or alpha 2-antiplasmin. In summary, the results demonstrate a tendency for increased levels of various coagulation factors and protein S in CAPD patients with no significant alterations in the levels of various fibrinolytic and endogenous anticoagulant agents, i.e. antithrombin III and protein C. The clinical significance and the mechanism responsible for the observed changes require further investigation.

Effect of hemodialysis on contact group of coagulation factors, platelets, and leukocytes

Earlier reports have suggested possible activation and consumption of factor XII during hemodialysis. To investigate this possibility, a series of in vivo and in vitro experiments were conducted using different dialysis membranes and two different dialysates (acetate and bicarbonate). Factors XII and XI activities, factor XII concentration, and high-molecular-weight kininogen were measured. In addition, platelet count, white blood cell count, and hematocrit were monitored. Contrary to the previous reports, no discernible consumption of factor XII, factor XI, or high-molecular-weight kininogen was found irrespective of the type of membrane or the composition of the dialysate used. Transient leukopenia was noted with cellulosic membranes, whereas none occurred with polyacrylonitrile dialyzers. The composition of dialysate did not affect the white blood cell count during dialysis.

Increased Levels of Protein C Activity, Protein C Concentration, Total and Free Protein S in Nephrotic Syndrome

Plasma protein C (PC) antigen concentration has been shown to be normal or increased in patients with proteinuria. However, the available data concerning PC anticoagulant activity in nephrotic syndrome (NS) are limited. We measured plasma PC antigen concentration. PC anticoagulant activity, total and free protein (PS) concentrations, and antithrombin III (AT-III) antigen concentration in 21 adult patients with NS. The results were compared with those obtained in a control group of normal volunteers. PC antigen concentration and its anticoagulant activity were significantly increased in the NS group when compared with the normal control group. Likewise, plasma total and free PS values were significantly higher in the NS patients than the corresponding values found in the control group. In contrast, plasma AT-III antigen concentration was significantly reduced in patients with NS. A negative correlation was found between plasma PC and AT-III levels. These observations suggest that increased plasma PC concentration and anticoagulant activity in NS may afford some protection against the thrombotic diathesis associated with antithrombin deficiency and other coagulation abnormalities in this otherwise hypercoagulable state.

Urinary excretion and deficiency of prothrombin in nephrotic syndrome

Plasma and urinary prothrombin concentration and plasma prothrombin activity were measured in a group of 17 patients with the nephrotic syndrome. An immunologic assay using a monospecific antibody against human prothrombin was employed in the measurement of prothrombin concentration in the plasma and urine. Prothrombin-deficient plasma was used as the substrate in the measurement of plasma prothrombin activity. A control group consisting of five normal volunteers was included for comparison. Both the activity and concentration of prothrombin were significantly lower in the nephrotic group as compared with the control group. Significant quantities of immunoreactive prothrombin were detected in the urine of the majority of nephrotic patients. This study has provided unequivocal evidence of urinary excretion and acquired deficiency of prothrombin in the nephrotic syndrome.

Coagulation abnormalities in patients with end-stage renal disease treated with hemodialysis.

Plasma levels of various blood coagulation factors, antithrombin III and plasminogen were measured in 18 patients with end-stage renal disease treated by long-term hemodialysis. The results were compared with those obtained in a group of normal volunteers. Factors XII, IX and II activities were significantly reduced; factors VIII, VII and X levels were increased; and factors XI and V activities and high molecular weight kininogen concentration were comparable to the control group. Antithrombin III activity and concentration were significantly reduced. The mean plasma fibrinogen concentration was normal although levels above and below normal limits were noted in a few patients. Similarly the mean platelet count was normal, although mild thrombocytopenia occurred in several patients and thrombocytosis in one. In conclusion, the present study confirms published results about factor VIII and AT-III, and provides new information on changes of other coagulation factors in uremia treated by long-term hemodialysis.

Extrinsic and Common Coagulation Pathways in End-stage Renal Disease Associated with Spinal Cord Injury

Data on the effects of combined long-standing spinal cord injury (SCI) and end-stage renal disease (ESRD) on blood coagulation system are limited. We studied the extrinsic and common pathways of blood coagulation system in 9 men with SCI-ESRD treated with maintenance hemodialysis. Plasma procoagulant activities of factors (F)VII, X and II were measured in a clotting assay using appropriate deficient plasmas as substrate. In addition, the antigen concentration of FII was measured using monospecific antibodies against human FII raised in goat in a gradient plate immunodiffusion system. Also measured were plasma fibrinogen concentration and platelet count. The results were compared with those obtained in a group of 10 ambulatory ESRD patients and 8 normal control volunteers. Plasma coagulant activity of FVII was markedly elevated and plasma fibrinogen concentration was moderately increased in SCI-ESRD patients: In contrast, plasma FII was mildly depressed while platelet count was within normal limits in SCI-ESRD patients. The data indicate that the combination of SCI and ESRD can lead to the alteration of the extrinsic and common coagulation pathways. Further studies are needed to elucidate the precise mechanism and the clinical significance of the observed abnormalities.

Hypomagnesemia and Renal Magnesium Wasting in Renal Transplant Recipients Receiving Cyclosporine

Following the adoption and use of cyclosporine as the drug of choice in the management of renal allograft recipients, several cases of symptomatic hypomagnesemia were noted. These observations prompted the current prospective study of serum concentration and urinary excretion of magnesium in 27 renal transplant recipients treated with cyclosporine and prednisone. Relevant laboratory measurements were obtained shortly before and regularly after transplantation. The results were compared with those obtained in a group of 17 allograft recipients treated with azathioprine and prednisone. The cyclosporine-treated patients showed a significant reduction in the serum magnesium concentration and an inappropriately increased urinary excretion and fractional excretion of magnesium, suggesting renal magnesium wasting. The observed hypomagnesemia required magnesium supplementation in nearly all cyclosporine-treated patients. In contrast, azathioprine-treated patients showed normal serum magnesium concentrations and required no magnesium supplementation. In conclusion, administration of cyclosporine in renal allograft recipients appears to be commonly associated with renal magnesium wasting and hypomagnesemia. Therefore, it is recommended that serum levels of magnesium be monitored regularly in renal allograft recipients receiving cyclosporine and that magnesium supplementation be employed as needed to avoid magnesium depletion.