Pre-emptive pediatric kidney transplantation or not?

BACKGROUND: Kidney transplantation prior to dialysis (pre-emptive kidney transplantation, PKT) has been controversial because of the paucity of clinical evidence to clarify the risks and benefits of PKT. Several authors have confirmed a significant advantage of PKT in the treatment of patients with end-stage renal disease (ESRD). The aim of this study was to examine the characteristics of patients who received PKT or non-pre-emptive kidney transplant (NPKT). METHODS: We used a cohort of 323 consecutive kidney-transplanted children (53% boys) from Hospital da Criança Santo Antonio, Porto Alegre, Brazil, who underwent transplantation between January 2000 and December 2010. RESULTS: The main causes of ESRD were congenital anomalies of the kidney and urinary tract (CAKUT) (39%) and glomerulopathies (27.5%). The 12-, 36-, 60-, and 90-months death-censored graft survival rates were 97%, 92%, 86%, and 76%, respectively, in the PKT group, and 87%, 79%, 72%, and 65% in the NPKT group (P < .05). CONCLUSIONS: The results of this study suggest that pre-emptive transplantation is beneficial (hazard ratio = 0.37; 95% confidence interval: 0.18-0.82). The main causes of graft loss (n = 67) were recurrence of primary disease (21%), chronic allograft injury (17%), and death with a functioning graft (16%). We recommend PKT as a better choice for transplantation whenever possible to minimize ESRD morbidity and provide better long-term patient and graft survival.

Collaborative Brazilian Pediatric Renal Transplant Registry (CoBrazPed-RTx): A Report From 2004 to 2013.

BACKGROUND: The Collaborative Brazilian Pediatric Renal Transplant Registry started in 2004 as a multicenter initiative aiming to analyze, report, and share the results of pediatric kidney transplantation in Brazil. Data from all pediatric kidney transplants performed between January 2004 and December 2013 were recorded electronically and periodically updated. All patients under 18 years old from the participating centers were enrolled. Demographic data, etiology of chronic kidney disease, and patient and graft survival were analyzed. From a total of 2443 pediatric kidney transplants performed in Brazil during the study period, we report data from 1751 pediatric renal transplants performed in 13 centers enrolled in the collaborative study. Median age at transplantation was 12.4 years, and most of recipients were male (56%). The most common underlying renal etiologies were obstructive uropathy (31%) and glomerulopathy (26%). METHODS: According to donor source, 1155 (66%) of transplants were performed with deceased donors (DD). Initial immunosuppression consisted mainly of tacrolimus, mycophenolate, steroids, and induction therapy with anti-IL-2R antibodies. RESULTS: One-year graft survival (death-censored) was 93% and 90% (log rank test, P < .01), respectively, for living donor (LD) and DD. Graft losses (15%) were most frequently caused by vascular thrombosis, chronic allograft nephropathy, death with functioning kidney, acute rejection, and recurrent renal disease. Recipients of DD had 2.02 (95% confidence interval: 1.14-3.59) times the hazard of graft loss compared with those of LD (P = .015). Patient survival rates at 1 and 5 years were 98% and 97% for LD and 97% and 93% for DD, respectively. The mortality rate was 3.8%, mainly as the result of infection and cardiovascular disease. CONCLUSIONS: The results of this collaborative pediatric transplant study are comparable to international registries. Our effort has been able to maintain an exchange of information, both among the participating centers and with other international registries.

Biocorrosion of magnesium alloys: a new principle in cardiovascular implant technology?

OBJECTIVES: To develop and test a new concept of the degradation kinetics of newly developed coronary stents consisting of magnesium alloys. METHODS: Design of a coronary stent prototype consisting of the non-commercial magnesium based alloy AE21 (containing 2% aluminium and 1% rare earths) with an expected 50% loss of mass within six months. Eleven domestic pigs underwent coronary implantation of 20 stents (overstretch injury). RESULTS: No stent caused major problems during implantation or showed signs of initial breakage in the histological evaluation. There were no thromboembolic events. Quantitative angiography at follow up showed a significant (p < 0.01) 40% loss of perfused lumen diameter between days 10 and 35, corresponding to neointima formation seen on histological analysis, and a 25% re-enlargement (p < 0.05) between days 35 and 56 caused by vascular remodelling (based on intravascular ultrasound) resulting from the loss of mechanical integrity of the stent. Inflammation (p < 0.001) and neointimal plaque area (p < 0.05) depended significantly on injury score. Planimetric degradation correlated with time (r = 0.67, p < 0.01). CONCLUSION: Vascular implants consisting of magnesium alloy degradable by biocorrosion seem to be a realistic alternative to permanent implants.

Lateral and anterior plating of intra-articular distal femoral fractures treated via an anterior approach.

Thirty-five patients with 36 displaced distal femoral fractures (16 AO-type C2 and 19 AO-type C3) were treated with an anterior approach and double plating and followed for an average of 7 (3-44) months. Bone grafting with allograft and demineralized bone matrix was used. Postoperative therapy included immediate ROM and non-weight bearing for 12 weeks. Two patients died during hospitalization and one was lost to follow-up. Reductions were near anatomic in all but three patients. Uneventful healing by 16 weeks occurred in 24/36 fractures. Double plating via the anterolateral approach minimized stripping of the medial side and improved controlled access to the distal femur.

Polymerized degradable hyaluronan--a platform for stent coating with inherent inhibitory effects on neointimal formation in a porcine coronary model.

Biodegradable hyaluronan (hyaluronic acid, HA) made insoluble by self-cross-linking in the presence of N-(3-dimethylaminopropyl)-N'-ethyl carbodiimide (EDC) has been used to cover stents. The maximum polymer-mass on a 16-mm stainless steel stent is approximately 2 mg. During manual crimping and simulated application, the loss of polymerized HA is negligible. The insoluble HA coating has an advantageous inherent antiproliferative effect regarding neointimal formation after local vessel wall injury (overstretch model) and leads to a reduced inflammatory response compared to uncoated stainless-steel stents, used as control, in undiseased pig coronary arteries, over a follow-up period of four weeks. Thus, cross-linked HA stent coating warrants further research as an interactive degradable biomaterial with an inherent inhibitory effect on neointimal formation as a possible biomatrix for local drug delivery to reduce restenosis rate.

Renoprotective effect of the angiotensin-receptor antagonist irbesartan in patients with nephropathy due to type 2 diabetes.

BACKGROUND: It is unknown whether either the angiotensin-II-receptor blocker irbesartan or the calcium-channel blocker amlodipine slows the progression of nephropathy in patients with type 2 diabetes independently of its capacity to lower the systemic blood pressure. METHODS: We randomly assigned 1715 hypertensive patients with nephropathy due to type 2 diabetes to treatment with irbesartan (300 mg daily), amlodipine (10 mg daily), or placebo. The target blood pressure was 135/85 mm Hg or less in all groups. We compared the groups with regard to the time to the primary composite end point of a doubling of the base-line serum creatinine concentration, the development of end-stage renal disease, or death from any cause. We also compared them with regard to the time to a secondary, cardiovascular composite end point. RESULTS: The mean duration of follow-up was 2.6 years. Treatment with irbesartan was associated with a risk of the primary composite end point that was 20 percent lower than that in the placebo group (P=0.02) and 23 percent lower than that in the amlodipine group (P=0.006). The risk of a doubling of the serum creatinine concentration was 33 percent lower in the irbesartan group than in the placebo group (P=0.003) and 37 percent lower in the irbesartan group than in the amlodipine group (P<0.001). Treatment with irbesartan was associated with a relative risk of end-stage renal disease that was 23 percent lower than that in both other groups (P=0.07 for both comparisons). These differences were not explained by differences in the blood pressures that were achieved. The serum creatinine concentration increased 24 percent more slowly in the irbesartan group than in the placebo group (P=0.008) and 21 percent more slowly than in the amlodipine group (P=0.02). There were no significant differences in the rates of death from any cause or in the cardiovascular composite end point. CONCLUSIONS: The angiotensin-II-receptor blocker irbesartan is effective in protecting against the progression of nephropathy due to type 2 diabetes. This protection is independent of the reduction in blood pressure it causes.

Factors predictive of outcome in severe lupus nephritis. Lupus Nephritis Collaborative Study Group.

In 1992, we published the results of a prospective, controlled trial of aggressive therapy (high-dose prednisone plus oral cyclophosphamide alone or with plasmapheresis) in 86 patients with severe lupus nephritis. During this study, remission (serum creatinine < or =1.4 mg/dL [< or =123 micromol/L] and proteinuria < or =330 mg/d of protein) in renal disease occurred in 37 patients (43%). To assess the long-term effect of remission on patient and renal survival, we now report the results of our extended follow-up of these patients. After an average of 10 years of follow-up in the 86 patients, patient survival rates at both 5 and 10 years were 95% in the group that had a remission and 69% at 5 years and 60% at 10 years in the no-remission group (P < 0.001). Renal survival rates were 94% at both 5 and 10 years in the remission group compared with 46% at 5 years and 31% at 10 years in the no-remission group (P < 0. 0001). Features predictive of remission included stable renal function after 4 weeks on therapy, category IV lesion, lower chronicity index, white race, lower urine protein excretion level at baseline, and lower baseline serum creatinine level. The features predictive of end-stage renal disease were higher baseline serum creatinine level, presence of anti-Ro antibodies, and failure to attain a remission. Thus, in patients with the most severe forms of lupus nephritis, a remission of clinical renal abnormalities is associated with dramatic improvement in long-term patient and renal survival.

The Irbesartan type II diabetic nephropathy trial: study design and baseline patient characteristics. For the Collaborative Study Group.

BACKGROUND: Diabetic nephropathy is the most common cause of end-stage renal disease in the developed world. Angiotensin-converting enzyme inhibitors have been demonstrated to be renoprotective in type I diabetes and are now the standard of care for both hypertensive and non-hypertensive type I diabetic patients with any level of proteinuria. The role of blockade of the renin-angiotensin system in type II diabetic patients is not defined. The Collaborative Study Group has initiated the Irbesartan Type II Diabetic Nephropathy Trial (IDNT), studying the effect of the angiotensin II receptor antagonist irbesartan on progression of renal disease and mortality in type II diabetic patients with overt nephropathy and hypertension. Here we report the study design and baseline patient characteristics. METHODS: To qualify, hypertensive type II patients, age 30-70 years, must have a 24 h urinary protein excretion of >900 mg and a serum creatinine 90-265 micromol/l (1.0-3. 0 mg/dl) in women and 110-265 micromol/l (1.2-3.0 mg/dl) in men. Three treatment arms include irbesartan, placebo and amlodipine, with every attempt made to achieve similar blood pressure levels in all treatment arms. A total of 1650 patients will be enrolled utilizing approximately 225 clinics worldwide. The primary outcome measure is time to event to the composite end-point of doubling of serum creatinine, end-stage renal disease or death. The secondary outcome measure is time to composite end-point of fatal or non-fatal cardiovascular events. The average length of patient follow-up is expected to be approximately 36 months. RESULTS: The baseline characteristics of the study subjects are: age 59+/-8 years, duration of diabetes 15+/-9 years, height 168+/-11 cm (5 ft 6 in), weight 87+/-19 kg (192 lb), body mass index 31+/-7 kg/m(2), blood pressure 156+/-18 mmHg/85+/-11 mmHg, serum creatinine 150+/-53 micromol/l (1.7+/-0.6 mg/dl), creatinine clearance 66+/-34 ml/min and 24 h urine protein 4.0+/-3.5 g/day.

Effect of intensive blood pressure control on the course of type 1 diabetic nephropathy. Collaborative Study Group.

Diabetic nephropathy is the most common cause of end-stage renal disease in the United States. We undertook a study to assess the impact of assignment to different levels of blood pressure control on the course of type 1 diabetic nephropathy in patients receiving angiotensin-converting enzyme (ACE) inhibitor therapy. We also examined the long-term course of this well-characterized cohort of patients receiving ACE inhibitor therapy. One hundred twenty-nine patients with type 1 diabetes and diabetic nephropathy who had previously participated in the Angiotensin-Converting Enzyme Inhibition in Diabetic Nephropathy Study who had a serum creatinine level less than 4.0 mg/dL were randomly assigned to a mean arterial blood pressure (MAP) goal of 92 mm Hg or less (group I) or 100 to 107 mm Hg (group II). Patients received varying doses of ramipril as the primary therapeutic antihypertensive agent. All patients were followed for a minimum of 2 years. Outcome measures included iothalamate clearance, 24-hour creatinine clearance, creatinine clearance estimated by the Cockcroft and Gault formula, and urinary protein excretion. The average difference in MAP between groups was 6 mm Hg over the 24-month follow-up. The median iothalamate clearance in group I was 62 mL/min/1.73 m(2) at baseline and 54 mL/min/1.73 m(2) at the end of the study compared with a baseline of 64 mL/min/1.73 m(2) and final 58 mL/min/1.73 m(2) in group II. There were no statistically significant differences in the rate of decline in renal function between groups. There was a significant difference in follow-up total urinary protein excretion between group I (535 mg/24 h) and group II (1,723 mg/24 h; P = 0.02). Thirty-two percent of 126 patients achieved a final total protein excretion less than 500 mg/24 h. Patients from groups I and II had equivalent rates of adverse events. In patients with type 1 diabetes mellitus and diabetic nephropathy, the MAP goal should be 92 mm Hg or less for optimal renoprotection, if defined as including decreased proteinuria. With the combination of ACE inhibition and intensive blood pressure control, many patients can achieve regression or apparent remission of clinical evidence of diabetic nephropathy.

Captopril-induced reduction of serum levels of transforming growth factor-beta1 correlates with long-term renoprotection in insulin-dependent diabetic patients.

The renoprotective effect of captopril on progression of diabetic nephropathy was demonstrated by the Collaborative Study Group Captopril Trial and might be independent of blood pressure. Because angiotensin II is known to stimulate the prosclerotic cytokine, transforming growth factor-beta (TGF-beta), we postulated that the renoprotective effect may be due to inhibition of TGF-beta1 production. TGF-beta1 levels were measured in serum at baseline and 6 months from patients in the captopril trial. TGF-beta1 analyses were performed on all available patient sera. Analysis was performed between the percent change in TGF-beta1 levels during the first 6 months versus the percent change in glomerular filtration rate (GFR) in the subsequent 2 years. TGF-beta1 levels increased by 11% (P = 0. 003) in the placebo group (n = 24), whereas there was a decrease of 14% (P = 0.01) in the captopril group (n = 34). There was an inverse correlation between the percent change in TGF-beta1 levels during the first 6 months and the percent change in GFR over the ensuing 2-year period in patients from both the placebo (r = -0.55, P = 0. 005) and captopril groups (r = -0.45, P = 0.008). In patients with initial GFR below 75 mL/min, there was an even stronger correlation in percent change in TGF-beta1 levels and percent change in GFR in both placebo (n = 9, r = -0.69, P = 0.03) and captopril groups (n = 21, r = -0.73, P = 0.0001). Our data suggest that captopril decreases TGF-beta1 levels in diabetic nephropathy and that changes in TGF-beta1 levels may predict the course of diabetic nephropathy.

Remission of nephrotic syndrome in type 1 diabetes: long-term follow-up of patients in the Captopril Study.

In 1994, we reported a 3.4 +/- 0.8 year follow-up of the eight patients who experienced remission of nephrotic syndrome during the Collaborative Study Group-sponsored, multicenter trial of captopril therapy in patients with type 1 diabetes with nephropathy (Captopril Study). Of the 409 patients randomized to treatment on the Captopril Study, 108 had nephrotic syndrome (24-hour proteinuria >/= 3.5 g of protein) at baseline. Of these 108 patients, 8 experienced remission of nephrotic syndrome (proteinuria

Typing of rabies virus isolates by DNA enzyme immunoassay.

BACKGROUND: Alternatives to antigenic typing are needed for epidemiologic surveys of the rabies virus associated with translocated coyotes and foxes, especially in areas where a closely related rabies virus is transmitted by striped skunks. OBJECTIVES: We developed and evaluated two enzyme based typing methods for rabies virus. The products of a reverse transcription-polymerase chain reaction (RT/PCR) of the nucleoprotein gene were hybridized to type specific probes and detected by enzyme assay after immobilization on microtiter plates. STUDY DESIGN: We tested RT/PCR products of 27 rabies isolates by two different DNA enzyme immunoassays (DEIA) and evaluated the quality of the results from the corresponding nucleotide sequence of the samples. RESULTS: Using a set of two probes, one of the DEIAs correctly identified 26/27 samples as variants of rabies virus associated with either skunks, foxes, or coyotes. The identity of one fox rabies sample was unresolved by this assay. The second DEIA correctly identified 24/27 samples as variants of rabies virus associated with either skunks, foxes, or coyotes. This assay did not resolve the identity of two fox rabies samples, and misidentified one fox rabies sample as a skunk rabies sample. CONCLUSIONS: DEIA can be used for epidemiologic studies of variants of rabies virus associated with skunks, foxes, and coyotes. Both DEIA methods were effective when typing probes recognized changes at a minimum of two nucleotide positions between variants, but only one assay method was sufficiently stringent to detect a single base pair mismatch. The inherent mutability of RNA viruses must be considered when designing and evaluating typing methods.

Inhaled nitric oxide and inhaled prostaglandin E1: effect on left ventricular contractility when used for treatment of experimental pulmonary hypertension.

OBJECTIVE: Pulmonary hypertension (PHT) is a life-threatening complication after isolated heart and lung transplantation. Recent work has shown that inhaled nitric oxide (NO) in combination with inhaled prostaglandin E1 (PGE1) reduce pulmonary hypertension but their influence on cardiac contractility is less well defined. METHODS: This study investigated left ventricular contractility as measured by the 'Preload Recruitable Stroke Work-Relation' (PRSW) in 24 anesthetized open chest pigs, 12 receiving in random order NO (50 ppm), PGE1 (20 microg/ml) and their combination compared to 12 controls. PHT was induced by embolization with glass beads (500 microm). Prior to induction of PHT, sonomicrometric crystals were placed on the heart to measure instantaneous cardiac dimensions. Instantaneous intraventricular pressure (micro-tip catheter) and intraventricular dimensions were recorded digitally, while intraventricular volumes were calculated from the intraventricular dimensions applying the cylindric ellipsoidal volume model for the left ventricle. PRSW was calculated from the instantaneous pressure and volume data during rapid vena caval occlusion by analysis of generated pressure-volume loops. All data were analyzed by MANOVA and corrected for heart rate (level of significance #: P < 0.05); PRSW-slope measures contractility, (PRSW-X-intercept did not change significantly). RESULTS: PRSW-change +/- SEM (in percent of initial PRSW after induction of PHT) was -14.6% +/- 4.4% versus 1.6% +/- 4.4% for NO versus Control (P = 0.004), -8.8% +/- 4.6% versus 1% +/- 3.3% (P = 0.18) for PGE1 versus Control and -5.7% +/- 4.4% versus 2.5% +/- 4.2% for NO + PGE1 versus Control (P = 0.33), respectively. In summary, application of NO 50 ppm significantly reduced left ventricular contractility while PGE1 20 microg/ml and the combination of NO and PGE1 did not. CONCLUSION: If NO is not available, the sole application of nebulized PGE1 (20 microg/ml) appears to be safe with respect to left ventricular contractility in the setting of PHT. The combination of NO and PGE1 for the treatment of pulmonary hypertension should be considered for clinical application in situations where a combination of pulmonary hypertension and decreased left ventricular function is present.

Molecular epidemiology of rabies epizootics in Texas.

BACKGROUND: Texas is in the midst of two independent epizootics of rabies, involving coyotes (Canis latrans) and domestic dogs (Canis familiaris) in southern Texas and grey foxes (Urocyon cinereoargenteus) in west central Texas. The domestic dog/coyote (DDC) and grey for (TF) rabies virus variants cannot be differentiated by antigenic typing with currently available monoclonal antibodies. These two variants also cannot be distinguished from a third variant, Sonora dog (SD) rabies, that is not enzootic in Texas, but occasionally occurs in animals along the western border with Mexico. OBJECTIVES: To determine a method for the differentiation of the DDC. TF and SD variants, which is essential for epidemiologic monitoring of the Oral Rabies Vaccination Program (ORVP), a program instituted to control rabies in coyotes and grey foxes in Texas. STUDY DESIGN: Primers complementary to nucleoprotein sequence of either the DDC or TF rabies virus permit specific reverse transcription and amplification by polymerase chain reaction. In addition, general primers, which recognize a broad range of rabies variants, used in conjunction with a restriction digest for the differentiation of DDC, TF of SD rabies virus were investigated. RESULTS AND CONCLUSIONS: Of 122 specimens tested with specific primers. 111 (91%) were specifically identified as either DDC (33 samples) or TF (78 samples). Overly stringent conditions, enzyme inhibitors, or limiting RNA may account for the 11 non-amplifications. Amplification of RNA under less stringent conditions, with primers recognizing a broad range of rabies variants followed by digestion with either restriction enzyme Desulfovibrio desulfuricans I (Dde I) or Haemophilus influenzae Rf. (HinfI), was used to identify the 11 isolates that did not amplify with specific primers (6 DDC, 4 TF and 1 SD). In addition to these 11 isolates, the less stringent method of amplification, followed by enzyme digestion has identified a total of 125 additional specimens (26 DDC, 94 TF and 5 SD) that were not tested by variant-specific amplification. These data provide a means to track the spread of the different rabies virus variants and allow the ORVP to plan its vaccine disbursement by defining the two epizootic boundaries.

Cost-effective poster and print production with digital camera and computer technology.

OBJECTIVE: The purpose of this report is to describe a cost-effective method for producing black-and-white prints and color posters within a radiology department. CONCLUSION: Using a high-resolution digital camera, personal computer, and color printer, the average cost of a 5 x 7 inch (12.5 x 17.5 cm) black-and-white print may be reduced from $8.50 to $1 each in our institution. The average cost for a color print (8.5 x 14 inch [21.3 x 35 cm]) varies from $2 to $3 per sheet depending on the selection of ribbons for a color-capable laser printer and the paper used. For a 30-panel, 4 x 8 foot (1.2 x 2.4 m) standard-sized poster, the cost for materials and construction is approximately $100.

Exogenous surfactant treatment before and after sixteen hours of ischemia in experimental lung transplantation.

OBJECTIVE: A syngeneic, acute, double lung transplant model in the rat was used to determine the impact of exogenous surfactant treatment on graft function after prolonged cold storage. METHODS: The donor grafts were flush perfused, preserved for 16 hours, and then reperfused for 120 minutes. Untreated lungs served as controls (group I). In group II the recipient received a 200 mg/kg dose of surfactant (CuroSurf) before reperfusion. In groups III and IV, surfactant was administered before perfusion and harvesting (III, 20 mg/kg; IV, 200 mg/kg). Serial measurements of graft pulmonary vascular resistance, alveolar-arterial oxygen difference, and compliance were obtained. Final graft assessment included weight gain and histologic study. RESULTS: Repeated-measures analysis of variance showed significant improvement of graft performance in respect to compliance, alveolar-arterial oxygen difference, and pulmonary vascular resistance in donor surfactant treatment group IV (200 mg/kg) in comparison with recipient treatment (group II) and untreated controls (group I). Reducing the donor surfactant supplementation from 200 mg/kg to 20 mg/kg (group III) improved oxygenation and lung compliance as compared with untreated controls. Grafts in groups I and II had significantly more weight gain after 2 hours of reperfusion. Recipient treatment resulted in significantly more pulmonary hemorrhage in histologic sections. CONCLUSION: Donor treatment with exogenous surfactant is advantageous for preservation of graft function after extended ischemia. Positive effects may be seen with as little as 20 mg/kg of exogenous surfactant given before donor organ perfusion.

Influence of dextrans on lung preservation: is the molecular weight important?

BACKGROUND: The addition of dextran with a molecular weight of 40,000 Dalton in pulmonary preservation solutions has proved to be beneficial. However, dextrans of other size have not yet been investigated. Therefore, it is unclear whether dextran 40,000 represents the optimal additive for lung preservation solutions. METHOD: In a working rat heart-lung model, lung were preserved with regular Euro-Collins solution or with Euro-Collins solution containing 5% dextran of different sizes: 40,000 Dalton molecular weight; 70,000 Dalton molecular weight; 160,000 Dalton molecular weight. After 2 hours of ischemia functional (oxygenation; pulmonary vascular resistance) and structural (wet/dry-ratio, light microscopy) data were assessed and the amount of dextran in the lung tissue was measured. RESULTS: Lungs preserved with Euro-Collins solution 70,000 Dalton molecular weight or Euro-Collins solution 160,000 Dalton molecular weight exhibited superior functional and structural results when compared with Euro-Collins solution and Euro-Collins solution 40,000 Dalton molecular weight. Additionally, the least amount of dextran in the lung tissue was found in organs preserved with Euro-Collins solution 160,000 Dalton molecular weight after ischemia and reperfusion. CONCLUSIONS: Dextrans are useful additives for lung preservation solutions. However, the size of the molecules is important because dextrans of 160,000 Dalton molecular weight were superior to dextrans of lower molecular weight in our study.

Treatment of recurrent rejection in heart transplantation: cytolytic therapy or bolus steroids?

OBJECTIVES: The treatment of recurrent rejection in heart transplant recipients has been a controversial issue for many years. The intent of this retrospective study was to perform a risk-benefit analysis between treatment strategies with bolus steroids only versus anti-thymocyte globulins (RATG; 1.5 mg/kg q 4 days). METHODS: Between 1986 and 1993, 69 of 425 patients (17 male, 52 female; mean age 44 +/- 11 years) who had more than one rejection/patient per month (rej/pt per mo) in the first 3 postoperative months were defined as recurrent rejectors. RESULTS: Repetitive methylprednisolone bolus therapy (70 mg/kg q 3 days) was given in 27 patients (group M; 1.4 +/- 0.2 rej/pt per mo) and RATG therapy for one of the rejection episodes of the 42 remaining patients (group A; 1.5 +/- 0.2 rej/pt per mo). The quality of triple drug immunosuppression in the two study groups was comparable. The rejection-free interval (RFI) following RATG treatment in group A was 21.6 +/- 10 days and 22 +/- 11 in group M. In group M, 3 of 27 patients (11%) had a rejection treatment-related infection (2 bacterial; 1 viral) versus 6 of the 42 patients of group A (14.2%; bacterial 1, viral 5). During postoperative months 3-24, 0.15 +/- 0.12 rej/pat per mo were observed in group M and 0.21 +/- 0.13 rej/pat per mo in group A (n.s.). In this 21-month period cytolytic therapy for rejection was initiated in 8 of the remaining 21 patients of group M (38%) and 15 of the remaining 37 patients of group A (40.5%). The absolute survival and the individual causes of death were not affected by the type of initial treatment of recurrent rejection. The actuarial freedom of graft atherosclerosis is comparable in the two groups with 78% in group A versus 79% in group M free of graft atherosclerosis at 3 years postoperatively. CONCLUSIONS: A comparison of cytolytic therapy versus repeated applications of bolus steroids for treatment of recurrent rejection reveals no significant difference in the long-term patient outcome with respect to the incidence of future rejection episodes and survival.

The urine protein to creatinine ratio as a predictor of 24-hour urine protein excretion in type 1 diabetic patients with nephropathy. The Collaborative Study Group.

The purpose of this study was to determine the usefulness of a random urine specimen protein to creatinine (P/C) ratio in predicting 24-hour urine protein excretion (24 UP) in type 1 diabetic patients with overt nephropathy. Two hundred twenty-nine outpatient diabetic subjects enrolled in the Collaborative Study Group's multicenter clinical trial of "Angiotensin-Converting Enzyme Inhibition in Type 1 Diabetic Nephropathy" provided specimens for study, which encompassed a wide range of proteinuria (0.05 to 13.3 g/d). Twenty-four hour urine collections for total protein and creatinine (g/d) were obtained in the outpatient setting. This was followed shortly thereafter by an untimed single urine specimen for protein and creatinine (mg/dL). For longitudinal analysis, 33 patients provided two 24-hour urine collections with concomitant random urine specimens, separated by at least a 3-month period. Across the range of proteinuria that we studied, the log random urine P/C ratio correlated to log 24 UP (r = 0.90). The regression line was almost identical to the line of unity, which indicates that a patient's 24 U/P (in g/d) can be predicted directly from the random urine specimen P/C ratio (P/C = 24 UP in g/d). However, the standard deviations associated with these predictions were large, especially at the higher 24 UP values. Of the 33 patients who provided two time-separated specimens, the direction of change in P/C ratio was discordant with the direction of change in 24 UP in 14 of the 33 repeat specimens.(ABSTRACT TRUNCATED AT 250 WORDS)