J.F. Moorhead

LIPID NEPHROTOXICITY IN CHRONIC PROGRESSIVE GLOMERULAR AND TUBULO-INTERSTITIAL DISEASE

It is hypothesised that chronic progressive kidney disease may be mediated by abnormalities of lipid metabolism. A series of self-perpetuating secondary events follows an initial glomerular injury. Increased glomerular basement membrane permeability leads to loss of lipoprotein lipase activators, resulting in hyperlipidaemia. Circulating low-density lipoprotein binds with glycosaminoglycans in the glomerular basement membrane and increases its permeability. Filtered lipoprotein accumulates in mesangial cells and stimulates them to proliferate and produce excess basement membrane material. The proximal tubular cells metabolise some of the filtered lipoprotein and the remainder are altered on passage down the nephron. Luminal apoprotein precipitates, initiating or aggravating tubulo-interstitial disease, if the intraluminal pH is close to the isoelectric point of the apoprotein. The hypothesis offers new approaches to the study of chronic progressive kidney disease by proposing a major pathogenetic role for lipid abnormalities.

Symptomatic cytomegalovirus infection in seropositive kidney recipients: reinfection with donor virus rather than reactivation of recipient virus.

74 patients receiving cadaver kidney grafts were investigated prospectively for cytomegalovirus (CMV) infection. Among seropositive recipients CMV infection, especially symptomatic and disseminated infection, occurred significantly more frequently when kidneys came from seropositive than from seronegative donors. Since seropositive recipients can become infected with donor virus, the excess is probably accounted for by reinfection. This conclusion was supported by restriction enzyme typing of virus isolates from recipient pairs receiving kidneys from the same donor; proven reinfection with donor strain virus was significantly commoner than proven reactivation of recipient virus. Furthermore, symptoms occurred only in the proven reinfection group. Although the proportion of reinfections that caused symptoms was less than that seen in primary infections, prior natural infection with CMV clearly does not prevent symptomatic reinfection in seropositive recipients, a point which has profound implications for future vaccination strategies in renal allograft recipients and choice of donors.

HYPOPHOSPHATAEMIC OSTEOMALACIA AFTER CADAVERIC RENAL TRANSPLANTATION

Abstract Seven patients with functioning renal transplants were found to have serum-inorganic-phosphate levels below normal, and five of them had X-ray evidence of osteomalacia Evidence for a phosphate leak came from abnormal high values for phosphate clearance and correspondingly low values for tubular reabsorption of phosphate. There was a slight metabolic acidosis. The cause of the phosphate leak is uncertain, but it could be that in these patients the proximal tubule is unduly sensitive to normal levels of parathyroid hormone.

THREE YEARS' EXPERIENCE OF CONTINUOUS AMBULATORY PERITONEAL DIALYSIS

Patients on continuous ambulatory peritoneal dialysis (CAPD) were studied for three years. 29 of them who had been on CAPD for six months or more were compared with patients on intermittent peritoneal dialysis (IPD) and on haemodialysis (HD). CAPD patients had significantly higher levels of HDL-cholesterol than HD patients. Urea, potassium, phosphate, and urate levels were significantly lower, and haemoglobin levels significantly higher, than in the IPD and HD groups. 43 CAPD patients studied had a peritonitis rate of 2.22 episodes per patient-year. CAPD offers an alternative form of dialysis to those unsuitable for HD, but until peritonitis rates can be reduced CAPD cannot rival HD as a long-term treatment.

INFLUENCE OF HL-A MATCHING, ANTIGENIC STRENGTH, AND IMMUNE RESPONSIVENESS ON OUTCOME OF 349 CADAVER RENAL GRAFTS: 3 Years' Experience of the London Transplant Group

Abstract Kidney-graft survival in 349 cadaver renal transplants followed up for between six months and two years after transplantation has been analysed. A significantly better survival is seen when donor and recipient are matched for three or more of the HL-A antigen sites, and a better prediction of graft survival is obtained when matching for 2nd locus antigens alone than for 1st locus antigens alone. The existence of a gene or series of genes controlling immune responses to HL-A antigens is postulated and a possible means of identifying its effects is presented with a view to the selection of potentially unresponsive recipients for whom an HL-A incompatible kidney graft may be acceptable. Preliminary results of the mixed-lymphocyte-culture tests performed between well-matched donors and recipients shows that the degree of stimulation parallels HL-A match grade.

PERSISTENT HYPOPHOSPHATÆMIA AND OSTEOMALACIA IN DIALYSIS PATIENTS NOT ON ORAL PHOSPHATE-BINDERS: RESPONSE TO DIHYDROTACHYSTEROL THERAPY

Four patients who had been on regular haemodialysis for periods of 3 1/2 to 7 years became hypophosphataemic with plasma-phosphate concentrations of 2.5 mg/dl or less before dialysis. None of them had been taking oral phosphate-binders for 2 years or more. Histologically all the patients had an excess of osteoid on bone biopsy. Intestinal absorption of phosphate and calcium was impaired, despite normal or high serum-25-hydroxycholecaliferol concentrations. Treatment with oral dihydrotachysterol resulted in corrections of the phosphate malabsorption and increases in plasma-phosphate concentration. The initial low plasma-phosphate values in these patients before dialysis probably reflected a state of phosphate depletion caused by the combination of malabsorption, loss during dialysis, and a low dietary intake.

Can urinary thyroid hormone loss cause hypothyroidism

Four patients presented with nephrotic syndrome associated with hypothyroidism; none had thyroid antibodies. Hypothyroidism resolved on remission of nephrotic syndrome in two patients; thyroxine (T4) replacement was ineffective during periods of gross proteinuria in another, and the fourth had had normal thyroid function a year before presentation. Urinary T4 excretion was measured in ten further patients with proteinuria. It was detectable in the urine in five, who had significantly lower serum free T4 (8.5 [95% confidence interval 5.8-11.2] vs 13.9 [11.1-16.7] pmol/l; p less than 0.01) and free triiodothyronine (3.1 [2.2-4.0] vs 4.9 [3.8-6.0] pmol/l; p less than 0.01) concentrations than the five patients without detectable urinary T4.

DISORDERS OF BLOOD-LIPIDS IN RENAL DISEASE

Hyperlipidaemia is a characteristic feature not only of the nephrotic syndrome but also of chronic renal disease without the features of that syndrome. There is evidence for disordered lipid metabolism in patients with chronic renal disease. In these patients the disordered lipid metabolism, the precise cause of which is unknown, is characterised by hypertriglyceridaemia, the aetiology of which is probably multifactorial. Hyperlipidaemia is an important potential risk factor in the aetiology of cardiovascular disease, which may be a leading cause of death in patients undergoing long-term maintenance haemodialysis therapy.

MULTICENTRE COLLABORATION IN 162 TISSUE-TYPED RENAL TRANSPLANTS: The London and Regional Transplant Group, March, 1969, to December, 1970

Abstract Between March, 1969, and December, 1970, the London and Regional Transplant Group, which includes twenty-one centres in the United Kingdom and Eire, has been concerned with the exchange of 162 cadaver kidneys for transplantation. By December, 1970, the number of potential recipients awaiting kidneys had increased to over 300, and the proportion of well to poorly matched transplants had become greater, so that more than 55% are now in the well-matched category. The results indicate that the ante-mortem management of the donor is much more important than ischaemic times per se for the subsequent performance of the transplants, in that kidneys from mechanically ventilated individuals were functionally superior. The findings with regard to the influence of the level of HL-A matching support the concept that this system is of major importance with regard to kidney-graft survival.

Plasma hydroxyproline fractions in patients with dialysis osteodystrophy

Plasma hydroxyproline fractions were measured in 17 normal subjects and in 54 patients on maintenance haemodialysis therapy (MHT) with various degrees of dialysis osteodystrophy. On the basis of both radiological and histological findings these patients were divided into three groups: radiologically normal, histologically normal and those with osteitis fibrosa. The mean total plasma hydroxyproline concentrations were significantly elevated in all groups of MHT patients. However, these increases were mainly due to peptide-bound and free hydroxyproline fractions. The highest values for these two fractions were found in patients with osteitis fibrosa. The free to peptide-bound hydroxyproline ratio was not significantly altered in the majority of patients on dialysis; the mean ratio was significantly lower in patients with osteitis fibrosa when compared with patients with no histological evidence of bone disease. This finding would suggest that there is no inhibition of hydroxyproline catabolism in patients on haemodialysis and the measurements of both free and peptide-bound hydroxyproline were equally sensitive in identifying patients with osteitis fibrosa.