I.S. Henderson

Influence of coexisting disease on survival on renal-replacement therapy

Survival of patients on renal-replacement therapy (RRT) is no longer improving. Increasingly, such patients are older and have co-morbid conditions affecting organs other than the kidney. In a retrospective study, we calculated actuarial survival of 375 patients starting RRT during a 6 1/2 year period at renal units in Aberdeen and Dundee, UK, after stratification of patients into three risk groups (low, medium, and high) based predominantly on co-morbidity and to a lesser extent on age. 2-year survival differed significantly between low, medium, and high risk groups both before (86%, 60%, and 35%, respectively; p < 0.002 for all comparisons) and after (90%, 70%, 46%; p < 0.004 for all comparisons) excluding early deaths (within 90 days of starting RRT). Overall survival was 61% in Aberdeen and 68% in Dundee (p = 0.04), but 73% and 74%, respectively, when deaths in the first 90 days were excluded (p = 0.73). We conclude that RRT is a highly successful treatment (86% 2-year survival) for patients aged under 70 with no co-morbid conditions (low-risk group); that coexisting non-renal disease has an important influence on survival of patients on RRT; and that risk stratification and analysis of data including and excluding early deaths should allow more valid comparison of data from different centres.

Erythropoietin and spontaneous platelet aggregation in haemodialysis patients

Erythropoietin significantly, reversibly, and reproducibly increased in-vitro whole-blood spontaneous platelet aggregation in 15 patients on haemodialysis. During erythropoietin treatment, spontaneous platelet aggregation was significantly higher in these subjects than in non-uraemic controls; concomitant treatment with 300 mg aspirin daily reversed platelet hyperaggregability. Erythropoietin may promote thrombosis by an effect on platelet function.

Oxygen free radicals and platelet and granulocyte aggregability in renal transplant patients.

Oxygen free radical reaction products (plasma malon-dialdehyde), the free radical scavengers plasma thiol and red cell Superoxide dismutase (SOD), and whole blood platelet and granulocyte aggregation were measured in 23 renal transplant patients and 23 age-matched controls. Malondialdehyde-like material (MDA) was significantly increased in transplant patients compared with controls (transplants MDA [median, range], 7.7 [5.3–11.5] nmol/ml; controls MDA, 6.3 [5.4–8.7] nmol/ ml; P<0.001). The patients also had increased red cell Superoxide dismutase (transplants SOD, 128.1 [89.4–93.8] U/0.5 ml red cells; controls SOD, 95.9 [62.0–132.6] U/0.5 ml red cells; P<0.001) and reduced plasma thiol (transplants thiol, 428 [266–496] ftmol/L; controls thiol, 445 [358–501] μmol/L; P<0.05). These factors were not influenced by immunosuppressive therapy, duration of transplantation, or creatinine concentration. Transplant patients had significantly higher levels of collagen-induced and spontaneous whole blood platelet aggregation compared with controls (collagen: transplants, 72 [4–93]%; controls 43 [6–94]%; P<0.001; spontaneous: transplants 46 [11–93]%; controls 37 [10–75]%; P<0.05). Spontaneous platelet aggregation, however, was significantly correlated with creatinine concentration (r=0.525, P<0.02, Spearmans correlation), and was raised only in those patients with a degree of renal impairment. Granulocyte aggregation was increased in patients receiving cyclosporine (CsA [n=15], 57 [36–66]%; no cyclosporine [n=8], 45 [37–62]%; controls [n=23], 39 [31–61]%; P=0.004). Renal transplant patients are subject to oxidative cell damage, and may be at increased risk of vascular thrombosis. Possible contributory factors include an immunological reaction to the graft and/or the effects of immunosuppressive therapy.

Platelet aggregation in erythropoietin treated dialysis patients.

Recombinant human erythropoietin is a successful treatment for the anaemia of renal failure. Its use has however been associated with thromboembolic complications. Changes in platelet number and behaviour in vitro were studied in: (1) 23 haemodialysis patients, and 10 continuous ambulatory peritoneal dialysis patients (CAPD) treated with erythropoietin (EPO); (2) 14 untreated dialysis patients (7 haemodialysis, 7 CAPD), with intrinsically high haemoglobins; and (3) 23 age-matched non-uraemic normal controls. All patients treated with erythropoietin had a significant rise in haemoglobin (23 haemodialysis patients: pre-EPO median (range), 6.9 (5.1-8.1)g/dl; post-EPO, 10.9 (9.0--12.8)g/dl; 10 CAPD patients: pre-EPO, 7.8 (6.7-8.8)g/dl); post-EPO, 12.5 (9.9-14.3)g/dl; p < 0.01). Platelet number was significantly reduced in CAPD patients (pre-EPO: 327 (210-745) & 10(9)/1; post-EPO: 240(198-359) & 10(9)/l; p < 0.01) but not in haemodialysis patients. Spontaneous and collagen-induced whole blood platelet aggregation were significantly increased following erythropoietin treatment, both in haemodialysis (spontaneous platelet aggregation: pre-EPO, 39(12-78)%; post-EPO, 64(27-93)%, p < 0.01, collagen-induced platelet aggregation: pre-EPO, 61(3-95)%; post-EPO, 74(21-93)% p < 0.05), and CAPD patients (spontaneous platelet aggregation: pre-EPO, 38(18-81)%; post-EPO, 71 (41-95)%, p < 0.01, collagen-induced platelet aggregation; pre-EPO, 73(28-95)%; post-EPO, 90(44-95)%, p < 0.05). There was no significant change in aggregation to 1 μM ADP. Spontaneous and collagen-induced platelet aggregation were significantly higher in erythropoietin treated patients and untreated CAPD controls with high haemoglobins compared to age and haemoglobin-matched non-uraemic normal individuals (23 normals: spontaneous platelet aggregation, 37(10-75)%; collagen-induced platelet aggregation, 43(6-94)%, p < 0.001). Enhanced platelet aggregability is associated with vascular disorders. The increased red cell mass due to erythropoietin therapy may have physical and chemical effects on platelet function predisposing to thrombosis in this susceptible group of patients.

TREATMENT OF SEVERE ACUTE VASCULAR REJECTION IN A RENAL ALLOGRAFT WITH MYCOPHENOLATE MOFETIL AND HIGH DOSE STEROIDS

A case of a highly sensitised haemodialysis patient who developed severe vascular rejection in her third renal allograft is presented. This severe rejection episode responded to mycophenolate mofetil (MMF) and high dose steroids.

Calcium carbonate 1250 mg/1260 mg: an effective phosphate binder.

Calcium carbonate is currently the first choice phosphate binder in renal failure. In the UK its most widely prescribed formulation is a combination of calcium carbonate 420mg and glycine 180mg (TitralacR 3M Riker). In order to achieve adequate reduction in the serum phosphate level, up to 12 of these tablets may be required daily. In a group of seven patients, we have compared Titralac with two alternative preparations containing calcium carbonate 1250mg (Calcium-500R Macarthys Medical Ltd) and calcium carbonate 1260mg (CalcichewR Shire Pharmaceuticals Ltd). Given at a third of the daily number of Titralac tablets, both these newer preparations were effective phosphate binders and produced no statistically significant change in serum calcium and phosphate. The important advantage of such a reduced tablet load is improved patient compliance with phosphate binder therapy. Calcium-500 is also a cost-effective treatment slightly reducing the cost when compared with combined calcium carbonate 420mg and glycine 180mg.

The effect of cefodizime on phagocyte function in non-patient volunteers and patients with chronic renal failure: In vitro and ex vivo studies

Cefodizime has previously been shown to possess a number of immunomodulating properties in vivo and in vitro using several different test systems. Since most in vitro studies have been performed with cells from normal individuals, we first investigated whether cells from chronic renal failure patients would respond in vitro to cefodizime in the same way as healthy subjects. Subsequently, we investigated the effect of cefodizime (10 gover 10 days in 2-g doses) on phagocyte function ex vivo in an open study of 26 chronic renal failure patients and 16 healthy subjects. Polymorphonuclear leukocytes were tested for their ability to polarize in response to cefodizime and/or f-met-leu-phe peptide. Polymorphonuclear leukocytes and monocytes were tested for their ability to produce chemiluminescence on stimulation with either phagocytic (zymosan) or soluble phorbol myristate acetate stimuli. Phagocyte and lymphocyte membrane receptor expression was compared after exposure to cefodizime. Exposure to cefodizime in vitro causes a significant increase in polarization of polymorphonuclear leukocytes from both normal individuals and renal failure patients (bothP<0.001). It also caused increased chemotaxis and chemokinesis in a modified Boyden chamber assay. Cefodizime did not affect lucigenin-enhanced chemiluminescence and there were only minor effects on cell membrane antigen levels. In the ex vivo study there was a significant increase in polymorphonuclear leukocyte polarization (P<0.001) attributable to cefodizime, but other investigations showed no significant differences. The results suggest that cefodizime may act as a mild priming agent for some functions, particularly chemotaxis.

Poor response to erythropoietin

EDITOR,--Iain C MacDougalls editorial on poor response to treatment with erythropoietin outlines a rational approach to this problem.1 We agree with his scheme of how to investigate and manage patients who apparently show resistance to erythropoietin but would strongly advocate one further investigation--namely, assay of plasma erythropoietin concentrations in such patients. …

Parathyroidectomy in Uraemic Hyperparathyroidism: A Clinical Study

Osteodystrophy is a common and sometimes debilitating complication of renal failure. Hyperparathyroidism plays a crucial role in the development of this condition. Significant morbidity is also incurred by the effects of calcium deposition in other tissues. We report a series of 27 patients undergoing parathyroidectomy between May 1988 and November 1989. All had biochemical, radiological and clinical evidence of hyperparathyroidism. Surgery was well tolerated leading to an improved quality of life and avoidance of the need for aluminium containing phosphate binders.