Victor Parsons

PLATELET PROTECTION AND HEPARIN SPARING WITH PROSTACYCLIN DURING REGULAR DIALYSIS THERAPY

When prostacyclin (5 ng kg-1 min-1) was given during dialysis it enhanced the biological activity of heparin and prevented the activation and consumption of platelets. No adverse effects were observed. The reduction in heparin requirements produced by prostacyclin should make dialysis, safer, particularly for patients at risk of bleeding, while preserving the biocompatibility of the dialysis circuit. It remains to be established whether prevention of platelet activation will confer long-term benefit by inhibiting the prothrombotic state induced by haemodialysis, thereby reducing the risk of atherosclerosis in uraemic patients.

Uremic Cardiomyopathy: Potential Role of Vitamin D and Parathyroid Hormone

44 patients receiving regular hemodialysis therapy were investigated using M-mode echocardiography and systolic time intervals to examine the effects of parathyroid hormone (PTH) and vitamin D on left ventricular function. 12 patients were treated with 1 microgram daily of 1, alpha-hydroxycholecalciferol for 6 weeks, which produced a decrease in plasma PTH concentration from 1,883 +/- 226 to 1,123 +/- 289 ng/l. Fractional fibre shortening (FS) increased from 34.6 to 37.6% (p less than 0.025) and mean velocity of fibre shortening (Vcf) increased from 1.21 to 1.32 circ/s (p less than 0.01). A second group of 20 patients was studied before and after the plasma magnesium concentration was increased from 1.25 to 1.70 mmol/l, resulting in a fall in plasma PTH concentration from 546 to 418 ng/l (p less than 0.001). This was associated with an increase in both FS from 32.4 to 34.3%, and Vcf from 1.19 to 1.21 circ/s. A third group of 6 patients with severe hyperparathyroidism underwent total parathyroidectomy, FS increased from 34.9 to 36.3% and Vcf increased from 1.22 to 1.38 circ/s. In conclusion, our results indicate that vitamin D and PTH do influence left ventricular function in uremic patients on chronic hemodialysis, and that a reduction in plasma PTH levels is beneficial to the uremic heart.

Aluminium in bone from patients with renal failure.

Some samples of bone from patients with renal failure contained more aluminium than others, and the concentration tended to be highest in patients who had been uraemic or on dialysis longest. The significance of the association of raised concentrations of aluminium in bone with renal failure is discussed.

SUBSTITUTION OF ALUMINIUM SALTS BY MAGNESIUM SALTS IN CONTROL OF DIALYSIS HYPERPHOSPHATAEMIA

For two years all 28 patients undergoing hospital haemodialysis were switched from a dialysate magnesium (Mg) of 0.85 mmol/l to one containing none. Oral aluminium hydroxide was discontinued, and magnesium carbonate was substituted as a phosphate binder. After 24 months on this regimen predialysis aluminium concentration had fallen significantly. There was no significant change in predialysis phosphate, which remained above the normal range; nor was there evidence of increased secondary hyperparathyroidism as judged by parathyroid hormone immunoassay and biochemical or clinical criteria. Predialysis Mg concentrations tended to fall towards the normal range. Aluminium-containing phosphate binders seem to be unnecessary for the control of dialysis hyperphosphataemia. Magnesium carbonate may be an alternative and less toxic compound.

PROGRESSION OF DIABETIC NEPHROPATHY

Although deterioration of renal function in diabetic nephropathy varies considerably from one diabetic to another, its rate is constant in individuals. For each patient there is a linear relation between period (months) which elapses from the time serum creatinine becomes greater than 200 mumol/l and the inverse the inverse of the serum-creatinine. The observation is of practical importance in predicting the time at which end-stage renal failure will develop, so that treatment can be planned in advance.

Fish Oil Modifies Lipids and Reduces Platelet Aggregability in Haemodialysis Patients

Haemodialysis patients have an exceptionally high incidence of death from cardiovascular causes, related in part to abnormalities of lipids and platelets. Eskimos, however, have a low incidence of myocardial infarction and have a high dietary intake of fish, rich in omega-3 polyunsaturated fatty acids. We have, therefore, studied the effect of a fish oil MaxEPA, containing 3.6 g of the omega-3 polyunsaturated fatty acid eicosapentaenoic acid on lipids and platelet function in haemodialysis patients. Following 8 weeks of therapy there was a 35% fall in triglycerides, a 10% rise of high-density lipoprotein (HDL) cholesterol, a 36% rise of HDL2 cholesterol fraction and a 54% rise of the HDL2:HDL3 cholesterol ratio. The platelet aggregation to adenosine diphosphate and collagen was significantly reduced. The activated whole-blood clotting time was prolonged from 141 to 153 s, and 69% of patients showed a reduction of factor VIII related antigen which is usually elevated in haemodialysis patients and is thought to be a marker of endothelial damage. The blood pressure fell from 147/82 to 124/74. We have thus shown that a dietary supplement of eicosapentaenoic acid produces potentially beneficial effects on lipids, platelets, and blood pressure and may help to protect against atheroma and thus cardiovascular mortality in high-risk haemodialysis patients.

Cimetidine: prophylaxis against upper gastrointestinal haemorrhage after renal transplantation.

The incidence of upper gastrointestinal haemorrhage within four months of renal transplantation was studied in two groups of patients. Thirty patients who received prophylactic cimetidine suffered no episodes of upper gastrointestinal haemorrhage, while six of the 33 patients who did not receive cimetidine suffered haemorrhages and one of them died as a result. The difference between the groups was significant. The results suggest that the prophylactic use of cimetidine in patients receiving renal transplants is worth while.

Aluminium-Induced Anaemia in Haemodialysis Patients

It appears well established that a microcytic, hypochromic anaemia is present in patients receiving regular haemodialysis treatment, who also suffer from chronic aluminium intoxication. This characteristic anaemia is slightly improved following deionization or reverse-osmosis treatment of dialysate water. Iron deficiency has been tentatively excluded as a cause of this anaemia by measurement of serum ferritin levels. The exact mechanisms involved in the pathogenesis of this anaemia are still to be fully elucidated but a disturbance in haem synthesis and porphyrin metabolism seems probable, and secondary effects of PTH in the bone marrow may be involved. Evidence has accumulated that aluminium is the most likely ion responsible for this anaemia but other ions, trace metals in excess or deficiency and potentially toxic substances cannot be excluded yet.

Effect of graft perfusion with two CD45 monoclonal antibodies on incidence of kidney allograft rejection.

In a blind trial, 77 patients were randomised to receive first cadaver kidney allografts that had been perfused either with a pair of CD45 monoclonal antibodies (mAbs), in an attempt to reduce the immunogenicity of passenger leucocytes, or with control human albumin solution. No complications of mAb perfusion were observed. Patient and allograft survival were similar in both groups. Rejection episodes were recorded in 7 (18%) of the patient with mAb perfused allografts compared with 24 (63%) of the controls.

Non‐insulin‐dependent Diabetes and Renal Replacement Therapy

Reports of renal replacement therapy in diabetes usually refer to patients with insulin‐dependent diabetes mellitus (IDDM) only, and little is known about renal failure in non‐insulin‐dependent diabetics (NIDDM). A high proportion, 46/141 (32%), of the diabetics treated at our unit since 1974 had NIDDM. They were older at treatment (56 ± 9 years, mean ± SD) compared to the IDDM patients (39 ± 10 years, p<0.001), and had a shorter duration of diabetes (13 ± 8 years versus 23 ± 8 years, p<0.001). Asians and Afro‐Caribbeans accounted for 48% of the NIDDM patients (22/46) compared to only 7% of those having IDDM (6/95, p<0.0001). Non‐diabetic renal disease accounted for the renal failure in 32% (15/46) of the NIDDM patients but only in 10.5% (10/95) of the IDDMs (p<0.001). Despite these differences the prevalence of other diabetic complications (retinopathy, neuropathy, and cardiovascular disease) was similar. Patient survival after transplantation was poorer in NIDDM than IDDM (23% and 57%, respectively, at 2 years). Survival on dialysis was equally poor in NIDDM and IDDM. Thus, NIDDM patients treated for renal failure are more commonly non‐European and more often have non‐diabetic renal disease. Yet other diabetic complications occur to the same extent in both IDDM and NIDDM patients with diabetic nephropathy.