Potential anti-ageing effect of chondroitin sulphate through skin regeneration.

OBJECTIVE: Skin ageing is inevitably exposed through its typical features such as wrinkles and sagging. Therefore, skin anti-ageing is a major issue in cosmetic research to prevent and improve ageing symptoms using effective ingredients. Chondroitin sulphate (CS), a type of glycosaminoglycan, is an important structural component of the extracellular matrix (ECM) and is involved in various biological processes, such as cell proliferation, differentiation and migration. Here, we aimed to investigate the effects of CS on skin regeneration and examine its efficacy as a potential safe and effective skin anti-ageing ingredient. METHODS: We investigated the effects of CS on cell proliferation in normal human keratinocytes and fibroblasts. Then, cell migration, ECM synthesis and related signalling pathways were examined in fibroblasts through gene and protein expression analysis. Finally, the effect on skin wound healing and regeneration was validated using a full-thickness skin wound model and an aged skin model. RESULTS: Chondroitin sulphate treatment increased the proliferation of keratinocytes and fibroblasts. It also stimulated the migration and synthesis of ECM components of fibroblasts. Further analysis revealed that CS induced the expression of type I procollagen by activating the extracellular signal-regulated kinase pathway. Using a full-thickness skin wound model and an aged skin model, we confirmed that CS treatment promoted skin wound healing and regeneration. CONCLUSION: Together, our results indicated that CS has the potential to facilitate skin regeneration, implying that CS could be clinically applied to improve skin ageing.

OBJECTIF: Le vieillissement cutané est inévitable, dans ses caractéristiques intrinsèques nous trouvons l'apparition des rides et l'affaissement de la peau. Sachant cela, l'anti-âge cutané est un enjeu majeur de la recherche cosmétique où sa prévention ou son amélioration sont faites à l'aide d'ingrédients efficaces. Le sulfate de chondroïtine (CS), un type de glycosaminoglycane, est un composant structurel important de la matrice extracellulaire (ECM) et il est aussi impliqué dans les divers processus biologiques, tels que la prolifération, la différenciation et la migration cellulaire. Dans le travail présenté ici, nous avons étudié les effets du CS sur la régénération de la peau et son efficacité en tant qu'ingrédient anti-âge cutané sûr. MÉTHODES: Nous avons étudié les effets du CS sur la prolifération cellulaire des kératinocytes et fibroblastes humains normaux. Ensuite, la migration cellulaire, la synthèse de la ECM et les voies de signalisation associées ont été examinées dans les fibroblastes par l'analyse de l'expression des gènes et des protéines. Finalement, l'effet sur la cicatrisation et la régénération cutanées a été validé à l'aide d'un modèle de plaie cutanée « full thickness ¼ et d'un modèle de peau âgée. RÉSULTATS: Le traitement au sulfate de chondroïtine a augmenté la prolifération des kératinocytes et des fibroblastes. Il a également stimulé la migration et la synthèse des composants de la MEC des fibroblastes. Une analyse plus approfondie a démontré que CS induisait l'expression du procollagène du type I en activant la voie de la kinase régulée par le signal extracellulaire. En utilisant un modèle de plaie cutanée « full thickness ¼ et un modèle de peau âgée, nous avons confirmé que le traitement CS favorisait la cicatrisation et la régénération des blessures cutanées. CONCLUSION: Dans l'ensemble, nos résultats ont indiqué que le CS a le potentiel de faciliter la régénération de la peau, ce qui implique que le CS pourrait être appliqué cliniquement pour améliorer le vieillissement cutané.

Diagnostic value of haemoglobin A1c in post-partum screening of women with gestational diabetes mellitus.

AIMS: The aim of this study was to evaluate whether women with gestational diabetes mellitus could be screened using HbA1c for glucose metabolism status at 6-12 weeks post-partum. METHODS: We enrolled 699 pregnant women diagnosed with gestational diabetes mellitus from October 2005 to December 2013. A 75-g oral glucose tolerance test (OGTT) and HbA1c measurement were performed at 6-12 weeks after delivery. RESULTS: The prevalence of overt diabetes and pre-diabetes were 5.2% (n = 36) and 49.1% (n = 343), respectively, when using the 75-g OGTT as the gold standard. HbA1c alone identified 2.9% (n = 20) as having overt diabetes and 32.2% (n = 225) as having pre-diabetes. When American Diabetes Association cut-offs were applied, the sensitivity and specificity for HbA1c to diagnose overt diabetes were 19.4% and 98.0%, respectively. Pre-diabetes, according to the HbA1c criterion, had 41.2% sensitivity and 72.2% specificity. The misclassifications identified 97 positive differences, 233 negative differences and 369 ties (P < 0.05). The area under the receiver operating characteristic curves for detecting diabetes and pre-diabetes were 0.615 [95% confidence interval (95% CI), 0.515 to 0.716] and 0.588 (95% CI, 0.545 to 0.630), respectively. CONCLUSIONS: HbA1c may not be sensitive enough for an accurate diagnosis, but it is highly specific for diagnosing overt diabetes at 6-12 weeks post-partum in women with previous gestational diabetes mellitus.

Efficacy and safety of teneligliptin, a novel dipeptidyl peptidase-4 inhibitor, in Korean patients with type 2 diabetes mellitus: a 24-week multicentre, randomized, double-blind, placebo-controlled phase III trial.

We assessed the 24-week efficacy and safety of teneligliptin, a novel dipeptidyl peptidase-4 inhibitor, in Korean patients with type 2 diabetes mellitus (T2DM) that was inadequately controlled with diet and exercise. The present study was designed as a multicentre, randomized, double-blind, placebo-controlled, parallel-group, phase III study. Patients (n = 142) were randomized 2 : 1 into two different treatment groups as follows: 99 received teneligliptin (20 mg) and 43 received placebo. The primary endpoint was change in glycated haemoglobin (HbA1c) level from baseline to week 24. Teneligliptin significantly reduced the HbA1c level from baseline compared with placebo after 24 weeks. At week 24, the differences between changes in HbA1c and fasting plasma glucose (FBG) in the teneligliptin and placebo groups were -0.94% [least-squares (LS) mean -1.22, -0.65] and -1.21 mmol/l (-1.72, -0.70), respectively (all p < 0.001). The incidence of hypoglycaemia and adverse events were not significantly different between the two groups. This phase III, randomized, placebo-controlled study provides evidence of the safety and efficacy of 24 weeks of treatment with teneligliptin as a monotherapy in Korean patients with T2DM.

Measurement of pulp blood flow rates in maxillary anterior teeth using ultrasound Doppler flowmetry.

AIM: To measure pulp blood flow rates of clinically normal maxillary anterior teeth of healthy adults using ultrasound Doppler flowmetry (UDF). METHODOLOGY: A total of 359 anterior teeth from 63 patients (mean age, 29.8 years; range, 22-52 years; 26 females and 36 males) were included. The data were collected according to tooth type (three groups: central incisors, lateral incisors and canines). An MM-D-K (Minimax, Moscow, Russia) ultrasound Doppler imaging instrument was used to measure pulp blood flow. Differences between the tooth types were analysed with one-way anova and a Bonferroni correction at the 95% confidence level. RESULTS: The mean average linear velocities during the systolic period (Vams) of the central incisors, lateral incisors and canines were 0.58, 0.58 and 0.52 cm s(-1) , respectively. There were no significant differences in the mean Vams between the tooth types (P > 0.05). CONCLUSIONS: Within the limitations of this study, the pulp blood velocities of clinically normal, maxillary anterior teeth of healthy adults were between 0.5 and 0.6 cm s(-1) . There were no significant differences in mean blood flow rates between maxillary central incisors, lateral incisors and canines.

Clinical characteristics and outcomes of Clostridioides difficile infection in the intensive care unit: a KASID multi-centre study.

BACKGROUND: Despite the growing clinical and economic burden of Clostridioides difficile infection (CDI), data on CDI in the intensive care unit (ICU) in the Asia-Pacific region are lacking. METHODS: This retrospective study analysed 191 patients who were treated with CDI in the ICUs of three hospitals in South Korea from January 2017 to May 2021. Backward-stepwise multiple logistic regression was used to identify factors influencing the treatment response and mortality. RESULTS: Fifty-eight patients (30.4%) were considered immunocompromised. The mean Charlson comorbidity index was 5.65 ± 2.39 (10-year survival rate: 21%), the APACHE II score was 20.86 ± 7.78 (mortality rate: 40%), the ATLAS score was 5.45 ± 1.59 (cure rate: 75%), and the SOFA score was 7.97 ± 4.03 (mortality rate: 21.5%). Fifty-eight (30.4%) of the CDI cases were severe and 40 (20.9%) were fulminant. Oral vancomycin or oral metronidazole was the most frequently first-line treatments (N = 57; 32.6%). The 10-day response rate was 59.7% and the eight-week overall mortality rate was 41.4%. Fulminant CDI (OR 0.230; 95% CI 0.085-0.623) and each one-unit increment in the SOFA score (OR 0.848; 95% CI 0.759-0.947) were associated with treatment failure. High APACHE II (OR 0.355; 95% CI 0.143-0.880) and SOFA (OR 0.164; 95% CI 0.061-0.441) scores were associated with higher mortality. CONCLUSIONS: High-risk patients in the ICU had a higher mortality rate and a lower cure rate of CDI. Further research is required to provide more accurate prediction scoring systems and better clinical outcomes.

High fat stores in ectopic compartments in men with newly diagnosed type 2 diabetes: an anthropometric determinant of carotid atherosclerosis and insulin resistance.

OBJECTIVE: The objective of this study was to analyze how fat partitioning in the liver, muscle and visceral compartments is altered by diabetes and age, and whether altered fat distribution is associated with a higher carotid artery intima-media thickness (C-IMT) and insulin resistance. METHODS: This was an observational study performed on 21 young healthy men (mean age + or - s.d., 28.6 + or - 3.8 years) and 73 men with newly developed type 2 diabetes (38 young (29.2 + or - 4.1 years) and 35 middle-aged (47.1 + or - 6.0 years) subjects). Abdominal visceral and subcutaneous fat areas, mid-thigh muscle attenuation and liver attenuation characteristics were determined; the mid-thigh muscle was divided into low- and normal-density muscle areas. RESULTS: The young and middle-aged diabetic subjects had higher visceral fat areas, higher liver attenuation and higher lipid-rich muscle (greater low-density muscle area and decreased muscle attenuation) when compared with healthy individuals; however, no differences were observed between the two diabetic groups. In contrast, the C-IMT increased with both age and diabetes. On the basis of multiple regression analyses, mid-thigh low-density muscle area and muscle attenuation were independently associated with the C-IMT, and the mid-thigh normal-density muscle area and muscle attenuation were independent factors of insulin resistance. CONCLUSIONS: High fat stores within ectopic compartments were observed at an early stage in the development of diabetes. Furthermore, altered lipid partitioning within muscle was independently associated with carotid atherosclerosis and insulin resistance.

Core shell structure for solid gas synthesis of LiBD(4).

The formation of LiBD(4) by the reaction of LiD in a diborane/hydrogen atmosphere was analysed by in situ neutron diffraction and subsequent microstructural and chemical analysis of the final product. The neutron diffraction shows that nucleation of LiBD(4) already starts at temperatures of 100 degrees C, i.e. in its low temperature phase (orthorhombic structure). However, even at higher temperatures the reaction is incomplete. We observe a yield of approximately 50% at a temperature of 185 degrees C. A core shell structure of the grains, in which LiBD(4) forms a passivation layer on the surface of the LiD grains, was found in the subsequent microstructural (electron microscopy) and chemical (electron energy loss spectrometry) analysis.

Visceral fat amount is associated with carotid atherosclerosis even in type 2 diabetic men with a normal waist circumference.

OBJECTIVE: Our objective was to investigate whether determination of the quantity of visceral fat has an additional benefit in assessing atherosclerotic burden in men with type 2 diabetes compared with the traditional measurement of waist circumference (WC) alone. METHODS: This was an observational study performed in 368 men with type 2 diabetes, consecutively enrolled in Diabetes Clinics. Common carotid artery far-wall intima-media thickness (IMT), WC and visceral fat thickness (VFT), as measured by ultrasonography, were measured for each subject. Abdominal and visceral obesity were defined as a WC >90 cm and a VFT > or =47.6 mm, respectively. RESULTS: Among subjects with abdominal obesity (n=174), 35 subjects did not have visceral obesity. In contrast, among the subjects without abdominal obesity (n=194), 88 patients had visceral obesity. Despite no differences in age, glucose control, lipid profile and treatment modalities, there was a significant difference in carotid IMT based on VFT strata, but not WC strata. The subjects without abdominal obesity, but who had visceral obesity, had a higher carotid IMT compared with subjects with abdominal obesity, but without visceral obesity (maximal, 0.94+/-0.35 vs 0.78+/-0.17 mm; and average, 0.74+/-0.19 vs 0.64+/-0.14 mm, respectively, P<0.001). CONCLUSIONS: Subjects having visceral obesity, regardless of a normal WC, showed a higher carotid IMT compared with those with increased WC, but less visceral fat. In addition to WC, a direct estimation for visceral fat may provide an additional role in assessing atherosclerotic burden in men with type 2 diabetes.

Diagnostic value of glycated haemoglobin HbA(1c) for the early detection of diabetes in high-risk subjects.

OBJECTIVE: The aim of this study was to assess the validity of fasting plasma glucose (FPG) and/or glycated haemoglobin (HbA(1c)) as screening tests for the early detection of diabetes in high-risk subjects. METHODS: A total of 392 subjects (149 male and 243 female) with risk factors for diabetes were included. All subjects underwent a 75-g oral glucose tolerance test and HbA(1c) measurement. Receiver operating characteristic curve analysis was used to examine the sensitivity and specificity of FPG and HbA(1c) for detecting diabetes, which was defined as a FPG > or = 7.0 mmol/l or a post-challenge 2-h plasma glucose > or = 11.1 mmol/l. RESULTS: The prevalence of newly diagnosed diabetes was 22.4% (n = 88). The current guideline of FPG > or = 7.0 mmol/l for diabetes screening detected only 55.7% of diabetic subjects. The optimal cut-off points of HbA(1c) and FPG for the diagnosis of diabetes were 6.1% (sensitivity 81.8%, specificity 84.9%) and 6.1 mmol/l (sensitivity 85.2%, specificity 88.5%), respectively. The screening model using FPG > or = 6.1 mmol/l and/or HbA(1c) > or = 6.1% had sensitivities of 71.6-95.5% and specificities of 77.6-95.7% for detecting undiagnosed diabetes. CONCLUSIONS: The current American Diabetes Association diagnostic criteria, based only on FPG, are relatively insensitive in the detection of diabetes in high-risk subjects. The simultaneous measurement of FPG and HbA(1c) might be a more sensitive screening tool for identifying high-risk individuals with diabetes at an early stage.

Can machine perfusion decrease the likelihood of discard among biopsied kidneys?

Many factors, such as donor risk factors and renal function, have been shown to be associated with an increased likelihood of discard after recovering kidneys from deceased donors. When these factors are insufficient for assessment, renal biopsy is often performed at the time of harvest to assess suitability. Our aims were to identify factors that predict the discard of a biopsied kidney and to assess the impact of machine perfusion (MP) on kidney discard. We biopsied 678 kidneys from deceased donors aged >or=40 years from 2001 to 2006. We used a logistic regression model to estimate the adjusted odds ratios for kidney discard. Thirty-nine percent (n = 261) of biopsied kidneys were discarded. Kidneys with glomerulosclerosis (GS) > 20% had the highest likelihood of discard. Other significant predictors of discard included extreme donor age, final resistance (>40), atherosclerosis, interstitial fibrosis, arteriolosclerosis, and terminal serum creatinine value (SCr) > 1.5 mg/dL. MP kidneys (n = 69) were less likely to be discarded than cold storage (CS) kidneys after adjusting for other factors (adjusted odds ratio = .13, P < .001). In conclusion, abnormal biopsy findings were associated with the highest likelihood of discard. MP was used in only 10% of the cases; however, the use of MP was associated with a decreased likelihood of discard among biopsied kidneys.

Factors associated with discard of recovered kidneys.

We reviewed diseased donor (DD) kidney usage at a single Organ Procurement Organization in Southern California to more closely examine factors associated with discard. From 2001 to 2006, 3863 kidneys from 1959 DDs were recovered, but 454 (11.8%) were subsequently discarded. Among the discarded kidneys, 211 (46.5%) were discarded based upon biopsy findings, 19 (4.2%) due to anatomical abnormalities, 16 (3.5%) based on donor quality, and 14 (3.1%) because they were felt to be too old to be pumped. Multivariate logistic regression analysis was performed using significant prognostic factors upon univariate analyses. According to the magnitude of the adjusted odds ratio (AOR), significant prognostic factors for discard were extreme donor age (AOR = 24.1 of age 70-80 years, P < .001; AOR = 6.34 age 50-69 years, P < .001; AOR = 2.77 age 40-49 years, P < .001; and AOR = 3.09 age <10 years, P < .001 vs age 10-39 years), high final resistance (AOR = 8.86 of >40 vs others, P = .006), glomerulosclerosis (GS) > 20% (AOR = 5.94 vs GS 0%-5%/no biopsy, P < .001), severe atherosclerosis (AOR = 4.66, P = .003), abnormal anatomy (AOR = 2.7, P < .001), and moderate or severe arteriolosclerosis (AOR = 2.2 vs none/mild/no biopsy, P < .001). Among biopsy findings, the presence of GS > 20% was associated with the highest likelihood of discard. A high final resistance increased the likelihood of discard as well. In conclusion, these findings may help to set the groundwork toward a more uniform approach to organ utilization in donor service areas.

Cloning, expression and regulation of Schizosaccharomyces pombe gene encoding thioltransferase.

The genomic DNA encoding thioltransferase was isolated from Schizosaccharomyces pombe using the polymerase chain reaction. The amplified DNA fragment was confirmed by Southern hybridization, completely digested with HindIII and BamHI, and then ligated into the yeast-Escherichia coli shuttle vector pRS316, which resulted in plasmid pEH1. The insert of plasmid pEH1 was transferred into the multi-copy vector YEp357 to generate plasmid pYEH1. The determined nucleotide sequence harbors an open reading frame consisting of four exons and three introns, which encodes a polypeptide of 101 amino acids with a molecular mass of 11261 Da. Thioltransferase activity was increased 1.6-fold in Saccharomyces cerevisiae containing plasmid pYEH1, and 1.8- and 2.7-fold in S. pombe containing plasmid pEH1 and pYEH1, respectively. The upstream sequence and the region encoding the N-terminal six amino acids were fused into promoterless beta-galactosidase gene of the shuttle vector YEp357R to generate the fusion plasmid pYEHR1. Synthesis of beta-galactosidase from the fusion plasmid was found to be enhanced by zinc and NO-generating S-nitroso-N-acetylpenicillamine.

Characterization and regulation of glutathione S-transferase gene from Schizosaccharomyces pombe.

A glutathione S-transferase (GST) gene has been cloned from Schizosaccharomyces pombe for the first time. The nucleotide sequence determined was found to contain 2030 base pairs including an open reading frame of 229 amino acids that would encode a protein of a molecular mass of 27017 Da. The cloned GST gene was expressed and was found to function in S. pombe, Saccharomyces cerevisiae, and Escherichia coli. The plasmid pGT207 encoding the S. pombe GST gene appeared to be able to accelerate the growth of a wild type S. pombe culture. In a culture of S. pombe containing plasmid pGT207, the growth was inhibited less by mercuric chloride than in a culture with vector alone. The 1088 bp region upstream from the GST gene as well as the region encoding the N-terminal 14 amino acids was transferred into the promoterless beta-galactosidase gene of plasmid YEp357R to yield the fusion plasmid pYSH2000. beta-Galactosidase synthesis was induced by cadmium chloride, mercuric chloride, hydrogen peroxide, and menadione. It was also induced by high temperature. These results suggest that the cloned S. pombe GST gene is involved in the oxidative stress response.

Suppression of post-hypoxic and post-encephalitic myoclonus with levetiracetam.

Posthypoxic and postencephalitic myoclonus is often poorly controlled with current treatments. The authors successfully treated three patients with posthypoxic and postencephalitic myoclonus by using levetiracetam, a new antiepileptic drug. Levetiracetam appears to be a promising agent for treating action myoclonus caused by hypoxic and encephalitic brain injury-the degree of functional improvement may depend on the severity of associated motor dysfunction.

5-HT1A receptor-mediated activation of G-protein-gated inwardly rectifying K+ current in rat periaqueductal gray neurons.

5-hydroxytryptamine (5-HT) has been reported to modulate analgesia produced by opioids or electrical stimulation of the periaqueductal gray (PAG). 5-HT increases K+ conductance and inhibits the firing activity of the PAG neurons. We examined the electrophysiological and pharmacological characteristics of the K+ current involved in 5-HT-induced hyperpolarization of dissociated rat PAG neurons. Among the neurons tested, 5-HT activated inward K+ currents in 30-40%, whilst the remaining 60-70% did not respond to 5-HT. 5-HT activated an inwardly rectifying K+ current (I5-HT) in a concentration- and voltage-dependent manner. I5-HT was mimicked by a 5-HT1A receptor selective agonist, 8-OH-DPAT, and was reversibly blocked by a 5-HT1A receptor antagonist, piperazine maleate, but not by a 5-HT2 receptor antagonist, ketanserin. I5-HT was sensitive to K+ channel blockers such as quinine and Ba2+, but insensitive to 4-aminopyridine, Cs+ and tetraethylammonium. I5-HT was inhibited by GDP(beta)s and was irreversibly activated by GTP(gamma)s. I5-HT was significantly suppressed by N-ethylmaleimide and pertussis toxin, but not by cholera toxin. Second messenger modulators such as staurosporin, forskolin, and phorbol-12-myristate-13-acetate did not alter I5-HT. The present study indicates that 5-HT-induced hyperpolarization of the PAG neurons results from activation of the pertussis toxin-sensitive G-protein-coupled inwardly rectifying K+ currents through 5-HT1A receptors.

Roles of protein kinase A and C in the opioid potentiation of the GABAA response in rat periaqueductal gray neuron.

The periaqueductal gray (PAG) is the main target site of the opioid-induced analgesia. The present study was designed to examine the roles of protein kinase A (PKA) and C (PKC) in the opioid-induced modulation of the currents activated by an inhibitory neurotransmitter, gamma-aminobutyric acid (GABA). The PAG neurons were acutely isolated and voltage-clamped under the nystatin-perforated patch-clamp mode. The GABA-activated current was sensitively blocked by a GABA(A) receptor antagonist, bicuculline, and selectively carried by chloride ions. The GABA(A) receptor-activated Cl(-) current was potentiated by a mu-opioid receptor agonist, [D-Ala(2),N-MePhe(4),Gly(5)-ol]-enkephalin acetate (DAMGO). The GABA response was also potentiated by phorbol-12-myristate-13-acetate (PMA). Pretreatment with PMA occluded the DAMGO potentiation. However, both chelerythrine and 2-[1-(3-dimethylaminopropyl)indol-3-yl]-3-(indol-3-yl) maleimide (GF109203X) also potentiated the GABA response. Pretreatment with chelerythrine or GF109203X also occluded the DAMGO potentiation. Meanwhile, the GABA response was potentiated by N-(2-[p-bromocinnamylamino]-ethyl)-5-isoquinolinesulfonamide (H-89), while not altered by forskolin. Pretreatment with H-89 occluded the potentiation effect of DAMGO on the GABA response. In addition, the DAMGO effect was completely blocked by pretreatment with forskolin. From the result, it can be suggested that activation of mu-opioid receptor potentiates the GABA(A) response through the mediation of PKA inhibition, and that PKC is not directly involved in the action mechanism of DAMGO.

Cytomegalovirus antibody status and renal transplantation: 1987-1994.

We examined graft and patient survival rates of 47,146 patients in the United Network for Organ Sharing registry following transplants between donors and recipients who were cytomegalovirus (CMV) antibody negative and positive. CMV positivity increased with age to about 80% in patients over 60. Seropositivity was seen in 80% of Asians, 71% of African Americans, and 56% of Caucasians. In all age groups, females had a slightly higher incidence of positivity than males. Transplants involving CMV-positive donors resulted in lower graft survival rates than those with CMV-negative donors. This occurred regardless of whether the recipient was CMV negative or positive. The greatest effect was on patient survival rate, which, in turn, adversely affected graft survival rate. The CMV-positive-donor effect was primarily noted in (1) Caucasian recipients, (2) patients with HLA-A,B,DR mismatches, and (3) patients older than 15 years of age. In contrast, CMV-positive donors were not a risk factor for African American and Hispanic patients, CMV-positive Asian patients, patients younger than 16 years of age, and patients with no HLA-A,B,DR antigen mismatches. In conclusion, a kidney from a CMV-positive donor is a risk factor for certain patients and currently yields about a 4% overall lower graft survival rate at 3 years than a kidney from a CMV-negative donor.

Patient death after renal transplantation--an analysis of its role in graft outcome.

Whether patient deaths among renal transplant recipients should be counted as transplant failures when they occur while the transplant is still functioning is a controversial issue. Analyses of more than 45,000 first cadaver transplants reported to the UNOS Scientific Renal Transplant Registry between October 1987 and March 1995 showed that deaths among transplant recipients were strongly associated with the patient's age and presence of insulin-dependent diabetes. Other factors associated with poor early graft function were also associated with a significantly increased risk of death. Deaths within the first 5 years increased from 9% of recipients aged 2-15 to 30% of those over age 45 (P < 0.001). Deaths with a functioning graft occurred in 2% of the youngest patients and 13% in the older age group (P < 0.001). Among diabetics, 32% died within 5 years (12% with a functioning graft) compared with 10% (6% with graft function) of patients with glomerulonephritis (P < 0.001). When the transplanted kidney failed to function immediately or the patient required dialysis during the first week after transplant, 30% of patients died within 5 years compared with 20% when the graft functioned (P < 0.001). There was no difference in the percentage of deaths with a functioning graft. We conclude that deaths among renal transplant recipients follow an expected pattern in which the likelihood of death increases with age and diabetes.

Analyses of the UNOS Scientific Renal Transplant Registry at three years--early events affecting transplant success.

The success of cadaveric renal transplants in the first year is determined largely by events that transpire during the transplant hospitalization. This conclusion is based upon analyses of data on 19,525 cadaver donor renal transplants performed since October 1987 and reported to the UNOS Scientific Renal Transplant Registry from more than 200 centers nationwide. Graft survival rates at 1 year differed by 20-30% depending upon whether or not the transplanted kidney functioned immediately and upon whether the patient required dialysis during the first week posttransplant, experienced rejection, or was discharged with a kidney that was functioning well. Recipients whose discharge serum creatinine level was less than 2.6 mg/dl or whose graft was functioning well at the time of discharge had 88% 1-year graft survival. A multistep logistic regression analysis showed cold ischemia time, transfusions, donor age and cause of death, HLA-DR mismatches, and peak sensitization to be significant factors in the first week. Prophylactic antilymphocyte antibodies (ALG/OKT3) reduced the incidence of rejection from 30% to 20% during the transplant hospitalization, but apparently only delayed rejection. By 6 months there was only a 3% reduction with ALG and a 5% reduction with OKT3 in the incidence of reported rejection and a 2% difference in 1-year graft survival. Although graft and patient survival are important measures of transplant success, graft survival is predicted upon both early and late events. The course of the transplant during the initial hospitalization and the quality of function at discharge were the strongest determinants of 1-year graft survival.

Effects of changes in the criteria for nationally shared kidney transplants for HLA-matched patients.

BACKGROUND: Nine years ago, a prospective trial began in all U.S. transplant centers to determine whether the results of renal transplantation would improve with the nationwide shipment of kidneys from cadaveric donors to HLA-matched patients. Since then, the stringency of criteria for HLA matching have been liberalized twice, from sharing only those kidneys that matched at all six HLA-A, -B, -DR antigens, to sharing phenotypically HLA-matched kidneys, and most recently to sharing zero HLA-mismatched kidneys. METHODS: Data reported to the United Network for Organ Sharing Scientific Renal Transplant Registry from October 1987 to December 1996 were analyzed to examine the transplant results of nationally shared HLA-matched kidneys and the effects of changes to the HLA matching criteria on graft survival and the distribution of HLA-matched kidneys. RESULTS: The overall 1-year graft survival rate of 5102 HLA-matched transplants was 88% compared with 81% for 58,207 recipients of kidneys with at least one HLA mismatch (P < 0.001). HLA-matched kidneys had a projected 12-year graft half-life, 50% higher than the 8-year half-life of mismatched grafts (P < 0.01). After the first change in the match criteria in August 1990, 1365 phenotypically matched kidneys with fewer than six HLA antigens identified had an 89% 1-year graft survival rate compared with 84% for 466 six antigen-matched kidneys transplanted before the change. After March 1995, 1067 zero HLA-mismatched kidneys that were not phenotypically identical nor six antigen matched, had a 1-year graft survival rate of 88%. Graft survival has not decreased as a result of these changes in the criteria for national sharing, despite an increase in the percentage of matched transplants from 2.5% during the six antigen-match era to 15.5% during the zero antigen-mismatch era. CONCLUSIONS: Changes to the United Network for Organ Sharing policy for national sharing of HLA-matched kidneys have increased the number of patients, and especially minority patients, who can benefit by receiving a well-matched graft without compromising the high graft survival rates provided by an HLA-matched kidney.