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PubMed1986

Renal function and laboratory evaluation.

This paper reviews the normal renal function in relation to common functional tests helpful to detect nephrotoxicity. The measurement of renal blood flow, intrarenal distribution of blood flow, and glomerular filtration rate remain the basic parameters of nephrotoxicity. Renal tubular function is accurately measured by standard clearance tests for solutes including electrolytes, glucose and amino acids. The renal concentrating capacity serves as a sensitive but non-specific measure of renal integrity. The measurement of plasma concentration of some solutes is helpful to identify nephrotoxicity, but is most effective when a profile of solutes is measured over a time period. Urinary protein excretion and particularly the excretion of enzymes may localize the nephrotoxicity in certain tubular segments. Due to the multiple functions of the kidney, no single test or group of tests can be relied upon to detect nephrotoxicity. A battery of tests including screening tests and specific tests to measure glomerular or tubular function must be selected to match the pattern of nephrotoxicity.

Amino Acids↗
PubMed1991

The UNOS Scientific Renal Transplant Registry--1991.

Based upon data reported to the UNOS Scientific Renal Transplant Registry between October 1987 and November 1991: 1. One-year graft survival rates were 79%, 73% and 62% for recipients of first (20,864), second (3,217), and multiple (673) cadaver donor transplants, respectively. 2. One-year graft survival rates were 94%, 89%, and 90% for first transplant recipients of kidneys from HLA-identical siblings (970), parents (1,487), and 1-haplotype-mismatched siblings (1,206), respectively. 3. Half-lives calculated after the first year were 7 years for cadaver donor transplants, 11 years for parent, 12 years for 1-haplotype sibling and, 27 years for HLA-identical sibling-donor first transplants. 4. The 1-year first transplant survival rate has improved from 78% in 1987-88 to 80% in 1990-91 transplants (p = 0.001). There has been an attendant decline in the percentage of broadly sensitized patients transplanted from 15% in 1987 to 8% in 1990 (p less than 0.01), which may have contributed to rising survival rates. 5. There has been a remarkable improvement in the 1-year graft survival of retransplanted patients from less than 70% in 1987-88 to 78% in 1990 (p less than 0.001). This improvement has been most notable in broadly sensitized patients and those with delayed graft function. 6. Diabetics who received a pancreas and kidney transplant (995) had 81% 1-year graft survival compared to 77% for those who received a kidney transplant only (p less than 0.002). 7. One-year graft survival rates decreased significantly in recipients of kidneys from donors aged under 16 or over 45. Survival was less than 70% when the donor was under 5 or over 60 compared to 81% when the donor was aged 16-45 (p less than 0.001) for recipients of first cadaver transplants. Delayed graft function occurred in 40% of cases when the donor was over 60 and 28% of cases when the donor was under 5. When function was delayed, survival was 50% for these marginal kidneys compared to 68% for younger adult kidneys with delayed function (p less than 0.001). Rejection also had a greater impact on survival of kidneys from donors under 5 or over 60. 8. The 1-year graft survival rate for 2,504 first transplant recipients of cadaver kidneys from young male victims of traffic accidents was 85%. The 1-year graft survival of 2,670 patients given kidneys from older female donors who died of cerebrovascular accidents was 73% (p less than 0.001).(ABSTRACT TRUNCATED AT 400 WORDS)

Adolescent↗
PubMed2006

Association of HLA class I antigen matching and early graft outcome in living donor kidney transplantation.

INTRODUCTION: HLA antigen matching often plays an important role in organ transplantation. As for HLA class I antigen matching, there are differences of opinion regarding its influence on the outcome of renal transplantations. The aim of this study was to evaluate the association of HLA class I antigen matching with early graft outcomes in living donor kidney transplantation. PATIENTS AND METHODS: We evaluated graft outcomes in the first month of transplantation. Major events were slow graft function (serum creatinine > 250 micromol/L at the end of first week), delayed graft function (patients requiring dialysis in first week), and acute rejection episode. Graft outcomes were compared for normal renal function (NRF, serum creatinine < or = 175 micromol/L) impaired renal function (IRF, serum creatinine > 175 micromol/L) or impaired graft function due to an acute rejection episode (IGF). RESULTS: The 115 subjects had a mean age of 29 +/- 8 years and their donors 38 +/- 11 years (P < .01). Immunosuppression included prednisolone, azathioprine, and cyclosporine. Parents, siblings, and others were kidney donors in 46%, 33%, and 21%, respectively. Comparisons between NRF/IRF (serum creatinine 133 +/- 24 vs 201 +/- 36 micromol/L, P < .01) and NGF/IGF (serum creatinine 146 +/- 44 vs 161 +/- 39 micromol/L, P < .05) showed no difference in number or pattern of HLA matching. CONCLUSION: HLA class I antigen matching may not produce an added influence on early graft outcome among living donor kidney transplantations.

Adult↗
PubMed1980

Evaluation of antitumor drug side effects in small animals.

This is an initial report on the development of screening tests for side effects of antitumor drugs, with small amounts of compound and short time intervals. These tests are based on acute dosing of mice and various blood or serum measurements: (a) total white blood cell count for leukopenia; (b) BUN for kidney toxicity; (c) SGPT for liver toxicity; and (d) creatine phosphokinase MB isozyme (CPK-MB) for cardiotoxicity. A correlation with the toxicity observed in other species is developed by establishing the effect of a prototype compound for each toxicity and tests of one or more compounds expected to lack such toxicity. On the basis of the limited number of compounds studied all four tests, although varying in sensitivity, seem to correlate with the results of tests in other species and with known effects in man. Final validation of these acute tests, especially the CPK-MB, will require both further study of histopathologic effects and correlation with results from clinical trials of an extended list of agents.

Alanine Transaminase↗
PubMed1975

Xenogeneic skin and kidney transplants in a closely related canine system, fox-dog.

Fox kidney and skin grafts were transplanted into dog recipients. Fox kidneys, transplanted en bloc into untreated dogs, survived 6.2 +/- 0.4 days. The skin transplants survived 5.9 +/- 1.4 days. The grafted kidneys showed almost normal function before rejection. Both skin and kidney rejection were mediated through a cellular mechansim. Performed natural antibodies against donor tissue were not present in the serum of the recipients. These results combined with absorption studies suggested a close relationship between fox and dog, but different number and morphology of chromosomes, immunoelectrophoretic patterns of serum proteins, and disparities of the transplantation antigens proved that the fox is a species quite separate from the dog. It was concluded that the fox-dog system, with its similarity to the chimpanzeeman relationship, offers a unique model to study clinically applicable methods of managing xenografts between closely related species.

Animals↗
PubMed2002

High transforming growth factor-beta and extracellular matrix mRNA response in renal allografts during early acute rejection is associated with absence of chronic rejection.

BACKGROUND: A case-control study was performed to investigate whether mRNA levels of transforming growth factor-beta (TGF-beta) and various extracellular matrix molecules in renal transplant biopsy specimens, taken during acute rejection episodes within 6 months of transplantation, discriminate between patients who show deterioration of graft function and develop chronic rejection (CR+ group), and those who do not develop chronic rejection (CR- group). METHODS: Patients in both the CR+ group (n=10) and the CR- group (n=18) had at least one biopsy-proven acute rejection episode within the first 6 months after transplantation. The two groups were similar with respect to donor-, recipient-, and transplantation-related clinical variables. Histologic changes (Banff classification) and the timing of the acute rejection episodes in the biopsies studied did not differ between groups. Renal cortical mRNA levels of TGF-beta1, collagen alpha1(IV), collagen alpha1(I), decorin, and the household gene glyceraldehyde-3-phosphate dehydrogenase in biopsy specimens taken during acute rejection episodes were quantified by real-time polymerase chain reaction. RESULTS: The mean TGF-beta mRNA level in the CR- group was 3.4 times higher than that in the CR+ group (P<0.04). The mean collagen IV, collagen I, and decorin mRNA levels in the CR- group were 4.2 times (P<0.05), 5.1 times (not significant), and 3.2 times (P<0.05) higher, respectively, than those in the CR+ group. The mean TGF-beta to decorin mRNA ratios between the two patient groups did not differ significantly. CONCLUSIONS: In summary, high mRNA levels for TGF-beta, collagen IV, and decorin, but not histopathologic changes, in biopsies taken during acute rejection episodes early after kidney transplantation are associated with absence of chronic rejection. We hypothesize that TGF-beta might have beneficial effects during acute rejection through its known antiinflammatory actions or as an inducer of tissue repair.

Acute Disease↗