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Biomedical subjects

J S Cheigh

Publications and source records attributed to J S Cheigh.

At least 37 records · Page 2Linked to original sources
PubMed1989

Hypertension in kidney transplant recipients. Effect on long-term renal allograft survival.

To examine the effects of hypertension on renal graft function, we studied the clinical course of 144 kidney transplant recipients who had functioning grafts for three to 13 years. The patients were divided into three groups: normotensive (n = 32), controlled hypertensive (n = 49) and uncontrolled hypertensive group (n = 63). In addition to the difference in their blood pressure status, the three groups had significantly different levels of serum creatinine at entry to the study (mean +/- SE in mg/dL: 1.41 +/- 0.02, 8.89 +/- 0.02 and 2.30 +/- 0.03, respectively, P = .0002). Cumulative graft survival (CGS) at ten years for normotensive patients was 81%, whereas it was 58% for controlled hypertensive patients and 50% for uncontrolled hypertensive patients. The difference of CGS between normotensive and hypertensive patients was significant (P = .01), whereas the difference between the two hypertensive groups, controlled v. uncontrolled, was not. If serum creatinine levels at entry to the study were adjusted and the CGS of hypertensive patients was compared to normotensive patients with comparable levels of serum creatinine, the differences in CGS between the two groups were no longer significant. Regression analyses for potential prognostic factors revealed that serum creatinine levels were of more primary importance as a prognostic variable than blood pressure status. We conclude that hypertension is an important risk factor for renal graft survival, but control of hypertension alone does not appear to improve it. Graft survival appears to be influenced more by the severity of graft dysfunction at entry to the study irrespective of blood pressure control.

Adolescent↗
PubMed1989

OKT3-associated adverse reactions: mechanistic basis and therapeutic options.

OKT3, a prototypic monoclonal antibody directed at the lineage-specific CD3 antigen expressed on mature T cells, is an effective immunosuppressant in organ graft recipients. Unfortunately, a variety of adverse reactions are observed following the first and second doses of OKT3. In a series of experiments designed to examine the signaling repertoire of OKT3, it was found that (1) OKT3 is an effective substitute for the alloantigen stimulus in the activation of antigen-specific memory T cells; (2) OKT3 is a potent inducer of cytolytic activity (secondary cytotoxic T-cell activity as well as natural killer-cell activity); (3) OKT3 is also an inducer of interleukin-2 and interferon gamma production; and (4) of the immunosuppressants currently in clinical use, cyclosporine greater than methylprednisolone greater than 6-mercaptopurine (an in vivo cleavage product of azathioprine) in curtailing T-cell activation with OKT3. Collectively, these observations suggest a potential mechanistic basis for the adverse reactions associated with OKT3 and provide experimental support for therapeutic strategies that include the use of cyclosporine and/or methylprednisolone before OKT3 administration.

Antibodies, Monoclonal↗
PubMed1989

Kidney transplantation in insulin dependent diabetic patients: improved survival and rehabilitation.

Between 1977 and 1986, 50 insulin-dependent diabetic patients received a kidney transplant, 19 from living related donors and 31 from cadaveric donors. Cumulative patient survival was 81% and graft survival was 64% and 33% for living related and cadaveric donor kidneys, respectively, at five years. These results are comparable to that of nondiabetic patients. While physical performance and visual acuity significantly improved after a successful kidney transplantation, neuropathies and angiopathies might not improve. Physical performance improved even in those patients whose nerve conduction time had deteriorated. These findings suggest that kidney transplantation is an effective means of improving survival and rehabilitation of diabetic patients with end-stage renal disease.

Adult↗
PubMed1987

Optimization of donor specific blood transfusion in kidney transplantation.

1. One hundred milliliters of stored whole blood DST, three times at weekly intervals is a practical, less immunizing and effective approach to enhance graft survival in recipients of a living-related donor kidney. 2. This protocol could also be used in sibling donor/recipient pairs who do not share a haplotype as well as in those who share two haplotypes to enhance graft survival. 3. The use of a short course of Cs (6 mg/kg/d for three weeks) along with DST appears to reduce the sensitization rate even lower. The dose of Cs used in this study produced no clinically significant adverse reactions, whereas Aza (1 mg/kg/d) often produces leukopenia. 4. DST produces significantly suppressed donor specific MLC responses in the early post-DST period; however, it increases the response at a later time. DST modulates immune responses in such a way that secondary responses upon grafting are more readily reversible by immunosuppressive agents.

Adult↗
PubMed1985

Impact of renal donation. Long-term clinical and biochemical follow-up of living donors in a single center.

Forty-six renal donors who responded to a questionnaire and two additional donors with nephrotic syndrome and renal insufficiency were studied. The mean age was 46 +/- 2.0 years (mean +/- SE). Duration of follow-up was 6 +/- 0.5 years. Serum creatinine levels increased from 1.0 +/- 0.03 mg/dl before donation to 1.2 +/- 0.04 mg/dl at follow-up. The incidence of proteinuria (more than 150 mg over 24 hours) was 39 percent. The serum creatinine level was 1.0 +/- 0.08 mg/dl and 1.2 +/- 0.06 mg/dl in the proteinuric and nonproteinuric groups, respectively. The incidence of hypertension was 31 percent with a serum creatinine level of 1.1 +/- 0.11 mg/dl and 1.2 +/- 0.07 mg/dl in the hypertensive and normotensive groups, respectively. One patient with nephrotic syndrome had proliferative glomerulonephritis. It is concluded that renal donation is associated with a minimal but statistically significant increment in serum creatinine levels. The incidence of mild hypertension and proteinuria is increased, but impact on renal function is minimal as assessed by serum creatinine determination.

Adolescent↗
PubMed1984

Induction of immune alterations and successful renal transplantation with a simplified method of donor-specific blood transfusion.

We developed a new and simplified donor-specific blood transfusion (DSBT) protocol for prospective kidney transplant recipients from one-haplotype-mismatched related donors. Prospective kidney donors gave 450 ml of blood in a quad-pack unit, and the blood was stored in a blood bank. Twenty-five patients were transfused with 100 ml of the respective donor's whole blood at 1, 8, and 15 days after its storage. After DSBT, only three (12%) developed donor-specific lymphocytotoxic antibodies. Following DSBT, donor-specific mixed lymphocyte culture (MLC) was significantly suppressed, without any accelerated (secondary-type) response in early MLC. In addition, sera obtained after DSBT also suppressed donor-specific MLC significantly. Sixteen recipients subsequently received a kidney transplant from the donor, and all had functioning grafts at three months, but one lost the graft thereafter (graft survival rate: 94% at 12 months). This study indicates that (1) 100 ml of stored whole-blood DSBT three times at weekly intervals is a practical, less immunizing, and effective approach to enhance graft survival in recipients of a one-haplotype-mismatched graft; and (2) immune consequences of DSBT include induction of donor-specific cellular and humoral adaptive responses that might be conducive to successful graft outcome.

Adolescent↗
PubMed1983

Systemic lupus erythematosus in patients with chronic renal failure.

The clinical courses of 36 patients with systemic lupus erythematosus (SLE) in whom chronic renal failure developed and who required dialysis for more than three months were studied. At the time dialysis was initiated, 14 of 36 patients (38.9 percent) had clinically active SLE, but only three of 24 (12.5 percent) had activity in subsequent years while receiving dialysis therapy. In the majority of patients, however, renal disease progressed to end-stage despite clinical quiescence of SLE. During the follow-up period (mean +/- SD, 36 +/- 39.8 months), eight patients died--six from infections and two from cardiac disease. Actuarial survival rates at one, two, and five years after dialysis treatment were 91.1, 78.8, and 68.9 percent, respectively. This study suggests that the progression of renal disease to end-stage in patients with SLE may be mediated by nonimmunologic mechanisms as well as SLE-related immunologic insults. In most of these patients undergoing long-term dialysis, SLE remains clinically inactive despite persistent serologic abnormalities. Survival of the patients undergoing dialysis is comparable with that of the general dialysis population.

Adolescent↗
PubMed1983

Focal segmental glomerulosclerosis in renal transplants.

This is a study of the incidence and clinicopathological significance of focal segmental glomerulosclerosis (FSG) in 154 renal allografts (22 biopsies, 128 nephrectomies and four necropsies) from 137 cadaveric and 17 living-related donors. FSG was identified in 18 grafts (11.7%) from 16 patients: six as recurrent FSG in four patients (two developed FSG in two consecutive transplants) and 12 as de novo FSG. The incidence of recurrent FSG in patients who had FSG as their original kidney disease was 30.8% whereas that of de novo FSG in patients who had renal diseases other than FSG was 8.7%. Histologically, recurrent FSG was characterized by mild degrees of obliterative arteriopathy of rejection and preferential involvement of the juxtamedullary glomeruli. Whereas, in de novo FSG, the occlusive vascular changes of rejection were severe and the glomeruli in the outer cortical region were mostly involved. Clinically, however, the differences between them were less clear, although nephrotic syndrome tends to occur more often and earlier in patients with recurrent FSG. Obliterative arteriopathy of chronic rejection and consequent glomerular ischemia appeared to be of major importance in the pathogenesis of de novo FSG in renal allografts.

Adolescent↗
PubMed1983

Natural history of cadaveric kidney transplants in the absence of early acute rejection.

The foremost goal in organ transplantation is to achieve normal graft function without rejection. 31 (8.7%) of 357 cadaveric kidney transplant had no evidence of rejection for the first 3 months. Among these, 2 patients died with a functioning graft and four grafts failed during the 1- to 7-year follow-up period. Actuarial graft survival rates of these patients were 96.8 and 79.0% at 2 and 5 years, respectively, as compared with 64.6 and 51.2%, respectively, for the controls (p less than 0.01). Multiple preoperative blood transfusions and the adjunctive immunosuppressive therapy with retroplacental gamma globulin appeared to be playing a role for the induction of the 'no-rejection' state. However, continuous immunosuppressive therapy is necessary to maintain graft function.

Adolescent↗
PubMed1983

The advantage of measurement of intact PTH in the prediction of clinical response and calcium metabolism after subtotal parathyroidectomy for renal osteodystrophy.

As previously reported, the circulating half-life of carboxyterminal PTH is greatly prolonged in renal failure (mean t1/2 33.20 +/- 10.18 hrs), while intact PTH is much less affected (t1/2 less than one hour). Preoperative intact PTH levels were strongly predictive of clinical response to subtotal parathyroidectomy, and may help to differentiate the nature of metabolic bone disease in symptomatic dialysis patients. Intact PTH levels showed strong correlation with postoperative calcium metabolism, allowing prediction of extent of postoperative hypocalcemia. Carboxyterminal PTH levels, influenced by renal function as well as by functional parathyroid state, were poorly predictive of response to parathyroidectomy and not correlated with postoperative calcium metabolism.

Adult↗
PubMed1982

Enhanced kidney graft survival with retroplacental source gamma-globulin. Results of a 5-year prospective study at a single center.

We examined the possibility that retroplacental source gamma-globulin (RPGG), with its content of anti-HLA antibodies, would improve cadaver kidney graft survival rates. In a 5-year controlled prospective study of 208 transplants, we found that the addition of RPGG to a standard immunosuppressive drug regimen (azathioprine and prednisone) resulted in significant improvement of the cumulative survival rate (CSR) of first and second grafts. At 2 years, the overall CSR of first grafts increased from a control value of 37% +/- 6 to 52% +/- 6 (P = 0.037). Among second graft recipients, the CSR increased from a value of 19% +/- 8 to 50% +/- 10 (P = 0.014). This improvement in graft survival was seen as early as 3 months after surgery and was sustained through 3 years without added recipient morbidity or mortality. When recipient populations were stratified for various factors, those groupings remonstrative of an intact or active humoral immune response capacity were found to have the highest survival rates in the study; 2-year graft CSRs of 70% +/- 6 and 65% +/- 10 were found in recipients with preformed antibody resulting from blood transfusions (P - 0.003) and cytomegalovirus infectivity (P = 0.0006), respectively. These findings indicate that the improved graft survival seen in this study may have resulted from a recipient's immunological response to challenge with RPGG.

ABO Blood-Group System↗
PubMed1981

Declining transplantability of prospective kidney transplant recipients.

The total number of cadaveric kidney transplants has been declining, despite an increasing dialysis population, greater understanding of transplant immunology, and improved transplant management. To explore the causes of this decline, various factors were studied in 140 dialysis patients who were awaiting transplantation and 100 consecutive recipients of cadaveric kidney transplants. The study indicates that there is a growing, now predominant, prospective kidney recipient population that is highly sensitized because of previous blood transfusions and kidney transplantations. As a result, 92% of the prospective recipients exhibit varying degrees of lymphocytotoxic antibodies. Thus, a major problem in clinical transplantation is the growing number of dialysis patients who are virtually untransplantable. The declining number of cadaveric kidney transplantations may be caused by, in part, changing immunologic characteristics in the recipient population.

Antilymphocyte Serum↗