Effect Of Renal Transplantation Research Articles

The effect of renal transplantation on hyperhomocysteinaemia in dialysis patients, and the estimation of renal homocysteine extraction in patients with normal renal function

Background: The pathophysiology of hyperhomocysteinaemia in chronic renal failure (CRF) is unknown. Possible mechanisms are decreased renal homocysteine (Hcy) catabolism or inhibition of extrarenal Hcy metabolism by uraemic toxins.Methods: We studied the short-term effect on plasma Hcy concentration of improvement of renal function after successful kidney transplantation (n=8), and determined renal Hcy extraction by measurement of total Hcy in arterial and renal venous blood in 7 cardiac patients with normal renal function.Results: Post-transplantation, plasma Hcy decreased with improving renal function. In the cardiac patients, no significant renal Hcy extraction could be demonstrated, but tubular disposal of the filtered load could not be excluded.Conclusions: Because loss of such renal metabolism could lead to hyperhomocysteinaemia in CRF, it is necessary to determine the renal extraction of free Hcy in subjects with normal renal function to further investigate renal homocysteine metabolism.

Effect of renal transplantation on pulmonary function in patients with end-stage renal failure.

Ten patients with end-stage renal failure on maintenance dialysis underwent serial lung function tests before and at monthly intervals after renal transplantation. Mean values of forced expiratory volume within 1 s, forced vital capacity, and total lung capacity were within the normal range before and up to 6, months after transplantation. The mean value of residual volume (RV) was above the normal range during all periods measured (157.8 +/- 21.5% predicted before transplantation and 121.2 +/- 17.0% predicted at 6 months after transplantation). No statistically significant changes in lung volumes were detected over a course of 6 months, but there was a trend for a reduction in RV after transplantation. The single-breath diffusion capacity for carbon monoxide (DLCO) was in the high-normal range before transplantation (115.7 +/- 9.5% predicted). It remained high at 1 month after transplantation (124.5 +/- 12.2% predicted), but it gradually came down to the normal range from the 2nd month onwards. At 6 months after transplantation the mean DLCO was 83.8 +/- 7.3% of predicted which was significantly (p < 0.0001) lower than the value before transplantation. We conclude that raised DLCO and RV values occurred in patients with end-stage renal failure on maintenance dialysis which were most likely the result of pulmonary vascular congestion, and these abnormalities tend to improve after renal transplantation.

Effect of Renal Transplantation on Serum Oxalate and Urinary Oxalate Excretion

Serum levels of oxalate are elevated in uremic patients on dialysis. The effect of living related donor kidney transplants on serum and urine oxalate levels was studied in 8 patients. Serum and urine oxalate levels were measured prior to transplant, on the day of transplant and daily for 5 days postoperatively, and the results compared to those in 11 normal subjects. All transplanted kidneys functioned immediately. Serum oxalate fell from 55 +/- 9 mumol/l (484 +/- 79 micrograms/dl) before transplant to 21 +/- 3 mumol/l (185 +/- 26 micrograms/dl) the day after transplant, and to 9 +/- 2 mumol/l (79 +/- 18 micrograms/dl) 72 h after transplant. Serum oxalate in normal subjects was 9 +/- 2 mumol/l (79 +/- 18 micrograms/dl). During the initial 24 h after transplant urine oxalate averaged 1,244 +/- 150 mumol/l (109.5 +/- 13.2 mg), but fell to levels not statistically different from normal by 72 h after transplant. Rapid clearance of oxalate after transplant leads to transient hyperoxaluria until normal levels of serum oxalate are reached.

Elevated serum immunoreactive inhibin levels in peripubertal boys with chronic renal failure

Boys with chronic renal failure have delayed progress through puberty and have raised gonadotrophin and low testosterone levels indicative of disturbed hypothalamo-pituitary-testicular function. Most studies into the mechanisms underlying the dysfunction have concentrated on the LH-Leydig cell interaction. However, it is now possible to probe the FSH-Sertoli cell axis by measuring plasma immunoreactive inhibin, which is a marker of Sertoli cell function. This study investigated the FSH-Sertoli cell (immunoreactive inhibin) axis in boys with chronic renal failure on conservative and dialysis treatment as they progressed through puberty. The effect of renal transplantation in chronic renal failure was also investigated. Blood was drawn at 15-minute intervals between 2000 and 0700 h from 51 boys with chronic renal failure at various stages of puberty. The samples were divided into two pools, corresponding to the hormone secretion in the first and second part of the night. Single blood samples were drawn from a group of normal boys between 0800 and 1000 h. A total of 37 normal boys and 51 boys with chronic renal failure were examined immediately before and during puberty. Of a total of 80 pulse profiles taken in chronic renal failure, 36 were from transplanted and 44 from non-transplanted uraemic subjects. Immunoreactive inhibin, FSH and testosterone were measured using standard radioimmunoassays. The subjects were pooled into pubertal stages I, II/III and IV/V for analysis of hormone data. Early morning levels of immunoreactive inhibin like molecules (i-Inh) rose steadily with pubertal progression for all subject groups, those for boys with chronic renal failure being significantly elevated over normal boys from pubertal stage II/III onwards. Uraemic boys had higher levels than those who had been transplanted at all pubertal stages (P < 0.05). Early morning levels of FSH were significantly higher in uraemic patients with pubertal stages IV/V compared to our normal boys. There were no differences in i-Inh levels in plasma pooled from the samples taken between 2000 and 0115 h and 0130 and 0700 h for either treatment group at any stage of puberty. Testosterone levels rose in the second part of the profile from pubertal stages II/III onwards for both treatment groups. The proportional increase of testosterone was lower by mid puberty in uraemic than in transplanted children (percentage increases of 92 +/- 29 and 569 +/- 190 respectively, mean +/- SEM). i-Inh failed to correlate with FSH at any Tanner stage or for any subject group. Peripubertal boys with chronic renal failure have highly elevated serum immunoreactive inhibin and FSH levels which are partially reduced by renal transplantation. There was no evidence of any relationship between i-Inh and FSH secretion in either normal boys or in uraemic or transplanted boys with the exception of a positive correlation in late pubertal patients after transplantation. Finally, despite problems associated with the current immunoassay for inhibin, this assay may still prove to be a useful marker of Sertoli cell function in testicular pathology.

The effect of renal transplantation and treatment with cyclosporin A on the prevalence of Raynaud's phenomenon

The prevalence of Raynaud's syndrome was assessed in 100 consecutive renal allograft recipients treated with cyclosporin monotherapy who were then converted to prednisolone and azathioprine. Prior to transplantation 56% were symptomatic for Raynaud's, following transplantation 36% improved, but with the introduction of cyclosporin 39% developed de novo symptoms. After withdrawl of cyclosporin symptoms improved in 89%, and withdrawal was associated with an increase in glomerular filtration rate from 67±7 ml/min/1 73 m2 (mean±sem) to 79 ± 7 (p&lt;0.05) and a reduction in plasma creatinine, from 167± 17 μmol/1 to 148 ± 11 (p&lt;0.05) and serum bilirubin from 13±1 μmol/1 to 10±0.5 (p&lt;0.05) and alkaline phosphatase from 13.5± 1 KAu/dl to 10.6 ± 0.6 (p&lt;0.05). This suggests that cyclosporin not only has an effect on increasing vascular resistance in the major blood vessels but also affects the microcirculation. Nifedipine, which has been shown to reduce some of the side effects of cyclosporin, reduced the prevalence of Raynaud's following transplantation.

Prolactin, thymulin and zinc in chronic hemodialysis: effect of renal transplant

The interrelationships between PRL, thymulin and Zn, were studied in 25 patients with chronic renal failure (CRF) undergoing kidney transplantation and immunosuppressed with cyclosporine A (CsA). The possible role of serum PRL levels in predicting allograft rejection was also investigated. Before the kidney transplant serum PRL levels were significantly higher than in normals (mean +/- SE, 28.3 +/- 7.1 vs 7.5 +/- 0.6 micrograms/l, p less than 0.001) and their response to TRH (200 micrograms iv) was impaired (mean delta % at peak, 45.4 +/- 9.5 vs + 641 +/- 47.5, p less than 0.001). After kidney transplantation a dramatic decrease in serum PRL concentrations was observed in all patients, followed by a slight upward trend in the following two weeks, while TRH test administered on 3rd, 7th and 14th day, induced a progressive increase in serum PRL responses (delta % at peak, 201 +/- 43.3, 220 +/- 37.1 and 305 +/- 15.5, respectively). No difference in serum PRL patterns was observed between patients with (8 cases) and without (17 cases) clinical features and kidney fine needle biopsies suggestive of rejection. Basal serum Zn levels of patients with CRF (18.1 +/- 0.6 mumol/l) were similar to those observed in normals (17.7 +/- 0.2 mumol/l) and without any correlation with serum PRL levels. A decrement in serum Zn was recorded during CsA infusion and on the first day after the surgery, followed by a slight and slow upward trend. Basal serum thymulin titers were low [2.92 +/- 0.18 (1/log2)], were further reduced after CsA infusion [1.68 +/- 0.15 (1/log2)] and returned to the pretransplant levels in the two weeks after grafting.(ABSTRACT TRUNCATED AT 250 WORDS)

The effect of renal transplantation on a major endogenous ligand retained in uremic serum.

The effects of renal transplantation on serum concentrations of 3-carboxy-4-methyl-5-propyl-2-furanpropanoic acid (CMPF) and indole-3-acetic acid (IAA), which are endogenous ligands retained in uremic serum, and on phenytoin binding to serum protein were investigated. IAA, a weakly bound ligand, was rapidly excreted by the transplanted kidney during the first one to three days after renal transplantation, but CMPF, a strongly bound ligand, was slowly excreted. The binding defect of phenytoin was partially corrected by transplantation during the period of study. The results suggested that the prolonged drug binding defect observed despite successful renal transplantation is caused by a slower decrease of strongly bound ligands such as CMPF retained in uremic serum; hypoalbuminemia, usually observed after transplantation, may also contribute to this phenomenon.

Effect of renal transplantation on zinc metabolism and taste acuity in uremia. A prospective study.

The effect of successful renal transplantation on zinc metabolism and taste acuity was determined prospectively in 15 adult uremic patients. Before transplantation all patients had subnormal concentrations of zinc in plasma and hair, as well as abnormal taste detection and recognition thresholds for sodium (salty), sucrose (sweet), hydrochloric acid (sour), and urea (bitter). Following renal transplantation, abnormalities of taste acuity and zinc metabolism persisted and were accompanied by increased urinary zinc excretion in all patients. Normalization of zinc concentration in plasma and hair as well as taste acuity did not occur until one year after transplantation and was associated with a concomitant decrease in urinary zinc excretion. The plasma zinc levels and daily urinary zinc excretion were inversely related (r = 0.62, P less than .001) in all patients with normal allograft function. None of the zinc parameters was significantly related to azathioprine or corticosteroid dosage. The results of this study suggest that zinc deficiency and taste abnormalities of uremia persist up to one year posttransplant and may be related to increased urinary zinc losses. The mechanisms underlying post-transplant hyperzincuria as well as clinical significance of zinc deficiency following transplantation remain to be determined.

Phenytoin binding and renal transplantation.

Limited data are available on the effect of renal transplantation on the abnormal phenytoin (PHT) binding found in uremic patients. We studied PHT binding before and after transplantation in eight patients. Return of PHT binding to normal correlated well with recovery of renal function. Correlations with serum albumin and free fatty acid levels were also studied.

The Effect of Renal Transplantation with a Minimal Steroid Regime on Uraemic Hypertriglyceridaemia

We have studied the lipid and associated biochemical indices in 18 renal transplant patients maintained on an alternate day prednisolone regime. At an average 27 months following transplantation serum lipids were not significantly different from normals despite some renal impairment in the transplant recipients. In addition the blood sugar and plasma immunoreactive insulin levels were elevated in transplanted patients. The intravenous fat tolerance test (IVFTT) was not found to be different from that of normals. In some patients IVFTT was performed before and after transplantation and it was shown that K2 (fractional removal rate of Intralipid) improved from abnormal to normal values. Thus, it has been demonstrated that previously abnormal lipid levels can return to normal after transplantation and this may be related to alternate day steroid regimes. Impaired removal of triglyceride seen in chronic renal failure is improved by transplantation.

Effect of renal transplantation on the levels of choline in the plasma of uremic humans.

Plasma choline levels were measured in patients who received a kidney transplant, in donors who underwent nephrectomy and in nonrenal surgical patients. Choline was measured using a choline kinase assay. Choline levels in patients receiving a kidney fell from 29.8 +/- 1.86 microM before transplantation to 15.7 +/- 2.32 1 day later; this normal level was maintained for at least 7 months and in a single case for 2 years. Kidney donors and nonrenal surgery patients showed a significant decrease in plasma choline on the day following surgery but choline levels returned to normal by 3 days after surgery. Thus a transplanted functional kidney reduced the high plasma choline levels, associated with uremia, to normal and maintained these normal levels throughout the period of observation.

Effects of renal transplantation on left ventricular size and function.

Thirteen patients with chronic renal failure and uraemia were investigated by echocardiography preoperatively before and after haemodialysis and again after a successful renal transplantation to evaluate the cardiac changes caused by renal transplantation. After renal transplantation, the left ventricular end-diastolic and end-systolic diameters, as well as the cardiac index, decreased, probably because of the decreased left ventricular filling pressure. The left ventricular wall thickness and mass decreased, apparently as a result of the decrease of the left ventricular preload and also of the decrease of the afterload, because the systolic blood pressure decreased. The left atrial diameter decreased in response to the decreased left ventricular preload and wall hypertrophy. The changes in the indices of left ventricular function as a result of haemodialysis appeared to predict the changes seen after renal transplantation. Renal transplantation appears to have a tendency to result in normal left ventricular and left atrial volumes, as well as to lessen left ventricular hypertrophy, without significantly improving left ventricular function.

The Effect of Renal Transplantation on Plasma Protein Binding

The in vitro plasma protein binding was determined in nine maintenance hemodialysis patients who later underwent renal transplantation. The organic acid fluorescein (10 micrograms/ml) or the organic base quinidine (5 micrograms/ml) was added to the pre and post transplant serum of these patients. Drug concentrations were measured spectrophotofluorometrically after equilibrium dialysis. The results were compared with the plasma protein binding of eight normal volunteers. The patients on maintenance hemodialysis had lower plasma protein binding of fluorescein than normals (78 +/- 5% vs 89 +/- 4, p less than 0.001). Plasma protein binding improved significantly after renal transplantation (85 +/- 3, p less than 0.01) but was still lower than in normals (p 0.05). Plasma protein binding of quinidine was not significantly different than in normal volunteers (77 +/- 8%) either prior to (72 +/- 10%) or after (73 +/- 12%) kidney transplantation. Plasma protein binding of quinidine remains unaffected by renal transplantation. However, the abnormal plasma protein binding or organic acids in chronic renal failure may be significantly improved by renal transplantation.

Effect of renal transplantation on pituitary gonadal function

Twelve adult male patients who had undergone successful renal transplantation were investigated. The gonadotropin responses to 100 μg luteinizing hormone-releasing hormone (LRH) were studied, and basal serum testosterone and prolactin assayed. Significantly elevated mean basal levels of luteinizing hormone (LH) and follicle stimulating hormone (FSH) were found, associated with a correspondingly excessive LH and FSH response to LRH. Mean basal serum testosterone levels in the posttransplant patients were significantly lower than in normal controls, while the mean basal prolactin levels were similar in the two groups. The results were not influenced by the varying degrees of renal function found in the posttransplant patients.

Effect of renal transplantation on marrow mast cell hyperplasia of chronic renal failure.

Marrow mast cells have been counted in iliac bone from patients with chronic renal failure treated by renal transplantation. Mast cell numbers were initially increased but returned to the normal range in many patients after renal transplantation. Improvement in osteitis fibrosa and osteomalacia after transplant was not clearly related to this diminution in the number of mast cells. The use of prednisone in renal transplant patients may have some effect in reducing the numbers of mast cells. There is no fully acceptable explanation for the increase in marrow mast cells which occurs in chronic renal failure.

Effect of renal transplantation on uremic deafness: A Long-Term study

In order to investigate the influence of a functioning transplant on uremic hearing loss, audiometrical controls were performed on 13 patients before and after renal transplantation. During renal dialysis treatment there was a marked hearing loss for the higher frequencies between 2 000 and 8 000 Hz. Hearing capacity improved to normal after transplantation, the best audiometric results being obtained 21.4 (8-42) months after surgery. There was a significant improvement in hearing especially for middle- and high-tone frequencies. It is assumed that uremic toxins, possibly responsible for sensorineural hearing loss in patients with chronic renal failure may be sufficiently removed by a functioning transplant.

Effect of renal transplantation on protein binding of drugs in serum of donor and recipient.

Blood samples were obtained periodically before and for about 3 mo after renal transplantation from a donor (mother) and a recipient (9-yr-old son with bilateral nephrectomy) for determination of serum protein binding of salicylate and sulfisoxazole. Ten days after the transplant, the recipient had an acute rejection episode which was treated successfully. The free fraction values of the drugs in serum of the recipient was considerably above normal before transplantation, decreased to normal within 2 days after transplantation, increased again several days before the rejection episode and remained elevated for about 50 days, and then returned to normal. Serum protein binding of the drugs in the serum of the donor was decreased for only a few days after transplantation and then returned to normal.

The value of bone density measurements in predicting the risk of developing avascular necrosis following renal transplantation

The effect of renal transplantation is, in most instances, to restore a functioning kidney which can respond to the metabolic status of the patient. The serum phosphate returns to normal, the serum calcium rises and the hyperparathyroid state, during maintenance dialysis, resolves in many cases. In a variable proportion of those patients who have received a renal allograft, structural bone failure may occur, within the next few years (2). This condition, aseptic necrosis, is a major influence in determining how quickly a recipient of a successful graft can return to a completely normal way of life. Its aetiology is still obscure; of importance may be continued hyperparathyroidism, steroid therapy or both (2).

Effects of renal transplantation on uremic neuropathy. A clinical and electrophysiologic study.

In three of 10 patients with uremic neuropathy improvement began two months after successful renal transplantation, and functional recovery was complete in a year, although residual clinical signs and electrophysiologic abnormalities remained. Of two patients with moderately severe polyneuropathy, one recovered in eight months, but an older patient had only partial recovery after a year. The remaining five cases were subclinical; in three of these, nerve-conduction velocities returned to normal in four to six months. Compressive mononeuropathy, an additional complication in two patients, also improved. Electrophysiologic studies suggest that segmental remyelination and nerve axon regeneration are both a part of the reparative process.