Renal transplantation after removal of anti-HLA antibodies.
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Antilymphocyte Serum↗
Biomedical subjects
Z Varghese
Publications and source records attributed to Z Varghese.
Pathogenic roles of post-heparin lipases in lipid abnormalities in hemodialysis patients.
The relative roles of hepatic lipase and lipoprotein lipase in the pathogenesis of uremic lipid abnormalities were studied in 92 hemodialysis patients. Fasting serum cholesterol, triglyceride, and HDL-cholesterol concentrations were measured. Plasma lipoprotein electrophoretic patterns were determined in all patients. Hepatic lipase and lipoprotein lipase activities were selectively measured in post-heparin plasma in 59 patients. Hemodialysis patients had higher serum triglyceride and lower HDL-cholesterol concentrations than did their age and sex-matched control subjects. Both hepatic and lipoprotein lipase activities were reduced in hemodialysis patients. An inverse relation between lipoprotein lipase activities and serum triglyceride concentrations emerged. Lipoprotein lipase activities correlated with in vivo post-heparin fractional clearance rates of Intralipid. A positive correlation between lipoprotein lipase activities and HDL-cholesterol concentrations probably reflected impaired catabolism of triglyceride-rich lipoproteins being responsible for the low HDL-cholesterol concentrations. Hemodialysis patients (41.3%) had an abnormal lipoprotein (the 'mid-band'). While hepatic lipase activities did not correlate with any parameters of lipid metabolism, patients with 'low' hepatic lipase activities had a significantly higher prevalence of 'mid-bands' than did those with 'normal' activities. No evidence was developed to prove that the 'mid-band' lipoproteins were remnant particles.
Adolescent↗
The enhancing and sensitizing effects of donor blood components, including dendritic cells, in a rat renal allograft model.
In the DA-to-Lewis renal allograft model, donor whole blood enhanced renal allograft survival (14.5 +/- 7.6 days versus 6.9 +/- 0.6 days in controls [P less than 0.01]). The effect of individual cell components given in numbers equivalent to those present in the enhancing volumes of donor whole blood was studied. Immunization with donor red cells alone produced greater enhancement than that produced by whole blood (36.14 +/- 19.5 days [P less than 0.01]). B lymphocytes also enhanced allograft survival (16.0 +/- 3.9 days [P less than 0.01]). Although slight enhancement was observed with platelets (8.5 +/- 0.6 days) and 10(5) dendritic cells (8.4 +/- 0.5 days), in terms of allograft function dendritic cell immunization produced evidence of dose-dependent accelerated rejection. A similar finding was obtained with donor T cell immunization. Donor plasma had no effect. We conclude that, although donor blood has an overall enhancing effect on renal allograft survival in this model, the sensitizing and enhancing effects can be ascribed to individual types of cells.
Animals↗
Post-heparin hepatic and lipoprotein lipase activities in nephrotic syndrome.
Lipid metabolism was studied in 18 patients with nephrotic syndrome due to various glomerulonephritides. Nephrotic patients had hypercholesterolemia with or without hypertriglyceridemia. The mean serum high-density lipoprotein cholesterol concentration was not significantly reduced in nephrotic patients. Hepatic lipase and lipoprotein lipase activities were measured selectively in post-heparin plasma from all 18 patients using a substrate-specific method. The mean lipoprotein lipase activity in nephrotic patients was markedly reduced while the mean hepatic lipase activity was not significantly different from that of controls. Lipoprotein lipase activities correlated inversely with serum triglyceride concentrations, but positively with in vivo post-heparin fractional clearance rates of Intralipid and with serum high-density lipoprotein concentrations. Nephrotic serum inhibited lipoprotein lipase activity in normal subjects. The percentage inhibition, however, did not correlate with the degree of hypertriglyceridemia. A relatively weak inverse correlation was shown to exist between plasma albumin concentration and hepatic lipase activities.
Adolescent↗
Hepatitis B virus and host cell membrane antigens on a primary hepatocellular carcinoma cell line.
We have defined some membrane antigens of the cultured hepatocellular carcinoma cell line PLC/PRF/5, which contains the integrated genome of hepatitis B virus. Using fluoresceinated antibodies, we identified HLA Class 1 glycoprotein and HB surface antigen on the membrane. Only in a minority of cells was physical association of these antigens demonstrated by co-capping. The presence of a "division" antigen was indicated by reactivity of the cells with the murine monoclonal antibody OKT9.
Animals↗
Focal glomerular sclerosis and nephrotic syndrome with partial lecithin:cholesterol acetyltransferase deficiency and discoidal high density lipoprotein in plasma and urine.
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Child↗
Digital vascular imaging and selective renin sampling in evaluation of vascular anatomy in renal transplant recipients.
Sixty-five renal transplant recipients underwent digital vascular imaging of the graft and simultaneous selective venous sampling for plasma renin activity. Renal artery stenosis was found in seven patients but did not appear to be functionally important. Diffuse intrarenal arterial attenuation was found in seven patients and was associated with impaired graft function and perfusion; it may indicate chronic rejection. Lower pole hypoperfusion was found in nine patients without impaired graft function or perfusion; its clinical relevance is uncertain. Aneurysmal dilatation of the main renal artery was found in two patients. Severe hypertension was common in patients with these three major abnormalities, but a causal association between the abnormality and hypertension could rarely be inferred. It may be the abnormalities on digital vascular imaging, especially diffuse intrarenal arterial attenuation and lower pole hypoperfusion, are secondary to severe hypertension. Digital vascular imaging with simultaneous selective venous sampling for plasma renin activity is useful in evaluating the vascular anatomy of the grafted kidney and in assessing any abnormality found. The combined procedure was well tolerated by all patients with no complications and no incidence of acute tubular dysfunction or proteinuria after the investigation.
Adolescent↗
Failure of sodium aurothiomalate and triethyl phosphine gold to cause renal tubular injury in rheumatoid arthritis: implications for the aetiology of gold-related nephropathy.
The urinary excretion of two proteins, B-2-microglobulin (beta 2M) and N-acetyl-B-D-glucosaminidase (NAG) was measured in 25 patients with rheumatoid arthritis (RA) on nonsteroidal anti-inflammatory drugs (NSAID). Although beta 2M excretion was normal NAG excretion was raised. As NAG excretion by a group of osteoarthritis patients receiving similar doses of NSAIDs was normal, it is concluded that rheumatoid disease per se may be associated with mild renal tubular dysfunction. Twelve of the above 25 patients were then given oral triethylphosphine-gold (auranofin) 6 mg daily and urinary beta 2M and NAG were measured after 6 months' treatment. Urinary excretion of beta 2M and NAG was also measured in 13 patients with RA established on intramuscular sodium aurothiomalate (MGST) and NSAIDs. Neither auranofin nor myocrisin were found to further significantly increase beta 2M and NAG excretion. These results suggest that gold compounds are not toxic to renal tubular epithelium.
Acetylglucosaminidase↗
Dissociation between calcium and phosphate absorption in nephrotic syndrome.
Intestinal calcium and phosphate absorption have been measured in nine patients with nephrotic syndrome and normal renal function, by a combined radioisotope technique which allows simultaneous measurement of both quantities. The values obtained were compared with those obtained in 20 normal controls. Calcium absorption in the nephrotic group was significantly lower than in the control group (P less than 0.01), but phosphate absorption in the nephrotic group did not differ from controls. This dissociation between calcium and phosphate absorption provides further evidence for independent mechanisms governing the two absorption processes.
Adolescent↗
Acyclovir in hepatitis B antigen-positive chronic liver disease: inhibition of viral replication and transient renal impairment with iv bolus administration.
Six patients with hepatitis B virus (HBV) related chronic liver disease were treated with acyclovir, 5-15 mg/kg 8 hourly, given as an iv bolus or iv infusion over 1 h for up to 7 days. Two patients treated with 10 and 15 mg/kg 8 hourly showed a decrease in HBV-DNA polymerase and HBV-DNA when mean trough acyclovir plasma concentrations of 5.0 +/- 0.6 and 13.2 +/- 3.0 microM were attained. Inhibition of viral replication was not seen in patients treated with lower doses. Transient renal impairment was seen in two patients who received high dosage by the iv bolus mode of administration. This complication may be prevented by a high oral fluid intake or iv infusion of the drug over 1 h. Further study with acyclovir 15 mg/kg 8-hourly given as an iv infusion for longer periods is warranted.
Acyclovir↗
Association of primary sclerosing cholangitis with HLA-B8.
The frequency of HLA antigens was studied in 25 patients with primary sclerosing cholangitis and compared with a control group of 562 kidney donors. Fourteen patients also had ulcerative colitis. A significant increase in the frequency of HLA-B8 (60%) was found in the primary sclerosing cholangitis patients compared with controls (25%) (p less than 0.001). HLA-B8 was found in eight patients with ulcerative colitis. The frequency of HLA-B12 was significantly decreased (8%) compared with controls (30%) (p less than 0.02). Piecemeal necrosis was observed on liver histology in 66% of HLA-B8 positive and 50% of HLA-B8 negative patients. Low titres of serum autoantibodies were frequently found in the primary sclerosing cholangitis group but did not correspond to the presence of HLA-B8. Raised serum concentrations of IgM and IgG were not related to HLA-B8. This study has shown that in patients with primary sclerosing cholangitis there exists a disease susceptibility gene closely associated with the B locus of the major histocompatibility complex which may be modified by other factors such as ulcerative colitis. Patients with ulcerative colitis and HLA-B8 may be particularly liable to develop primary sclerosing cholangitis.
Autoantibodies↗
Insulin resistance and iron overload.
Glucose tolerance tests performed in 15 patients (10 males and 5 females, age range 6-34 years, mean 16 years) with transfusional iron overload revealed fasting and subsequent blood glucose concentrations within the normal range in all except one patients who was overtly diabetic. However, in all patients except one, blood glucose concentration at 2 hours was higher than the respective fasting glucose concentration. All but two of the patients (one of whom was diabetic) showed fasting and post glucose hyperinsulinism. All the patients had hepatic dysfunction of varying severity. It is hence suggested that the initial disturbance of carbohydrate metabolism in transfusional siderosis is insulin resistance, similar to that found in chronic liver disease. Overt diabetes is probably a later event, occurring when sufficient damage to pancreatic cells has occurred and appropriate hyperinsulinaemia cannot be sustained.
Adolescent↗
Nephrotoxicity of ionic and non-ionic contrast material in digital vascular imaging and selective renal arteriography.
We assessed the nephrotoxicity of ionic and non-ionic radiocontrast material (CM) in two groups of patients in a prospective study. One group of 25 potential live kidney donors was studied following conventional renal angiography, carried out as part of the routine pre-operative assessment. The other group of 49 renal transplant patients with varying degrees of renal impairment was studied following digital vascular imaging carried out for investigation of hypertension. Plasma creatine, urinary N-acetyl-D-glucosaminidase (NAG), urinary microglobulin (B2M) and urinary protein excretion were measured before and after the imaging procedure. There were no significant changes in these parameters following digital vascular imaging, but there were increases in plasma creatinine (p less than 0.005) and urinary NAG creatinine ratio (p less than 0.002) in the conventional angiography group following the procedure. Substantial proteinuria developed in 35% of patients following conventional angiography. The differences in nephrotoxicity of radiocontrast agents during the two procedures could not be accounted for by the dose of material used, but probably reflect the effect of differences in the route of administration on the maximal concentration of the material reaching the kidney. Non-ionic radiocontrast material proved less toxic than ionic and may be preferable in conventional angiography.
Acetylglucosaminidase↗
Blood transfusion for renal transplantation: benefits and risks.
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Antibody Formation↗
Digital vascular imaging and selective renin sampling in post-transplant hypertension. Which kidney is responsible?
Forty-four hypertensive transplant patients were investigated by digital vascular imaging of the graft and simultaneous selective venous sampling for plasma renin activity to attempt to identify those patients whose hypertension may be amenable to surgical treatment. Localization of renin hypersecretion was possible in 12 patients. In ten of these, hypersecretion originated from the native kidney and in two from the graft. Localization was possible in a significantly higher proportion of patients with severe hypertension (8 of 17), and all of these had native kidney hypersecretion. Bilateral nephrectomy may be indicated in these patients. No cases of functionally significant renal artery stenosis were identified. The other major types of abnormal vascular pattern found on digital vascular imaging, diffuse intra-renal arterial attenuation and lower pole hypoperfusion may be secondary to hypertension. This combined technique may be useful in the evaluation of post-transplant hypertension, especially when hypertension is severe.
Adult↗
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.
Apoproteins↗
Plasma LCAT activities in renal allograft recipients.
Plasma LCAT activities were measured in 51 renal allograft recipients as well in 18 patients before and after successful renal transplantation. The mean plasma LCAT activity of the 51 patients did not differ significantly from that of 27 normal subjects. When the patients were separated into two groups according to whether they had normal or impaired renal function, there was no significant difference in their mean LCAT activities. Plasma LCAT activities correlated significantly with total cholesterol and total triglyceride concentrations. The sequential study demonstrates that the low plasma LCAT activities in uraemic patients rose towards normal after successful transplantation. At the same time, total cholesterol and HDL-cholesterol concentrations also increased. The increase in LCAT activity after renal transplantation is due to increased concentrations of the enzyme and probably reflects increased turnover of triglyceride-rich lipoproteins.
Adult↗
Hypophosphataemia after parathyroidectomy in chronic renal failure.
Out of 24 patients receiving haemodialysis who were subjected to parathyroidectomy, 13 developed hypophosphataemia; this persisted for 3-52 weeks (mean 10.6 weeks). Before operation these 13 patients had had significantly higher plasma alkaline phosphatase activities (p less than 0.01) and significantly higher values in iliac crest bone biopsy samples for active resorption surface and active formation surface (p less than 0.05 in each case) than the group who remained normophosphataemic. Significantly more of the patients who remained normophosphataemic had shown periarticular calcification in preoperative skeletal radiographs (p less than 0.001). Hypophosphataemia may result from reduced mobilisation of phosphate from bone or its increased accretion into bone, and resorption of phosphate from periarticular mineral deposits may protect against development.
Adult↗