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Objective: The purpose of the study is to review our experience with patients over 80 years of age with end-stage renal disease (ESRD) treated with continuous ambulatory peritoneal dialysis (CAPD)., Design: The records of all patients over 80 years of age treated in our unit with CAPD since 1979 were reviewed., Setting: Out-patient CAPD facility., Patients: Eighteen patients over 80 years of age were identified and studied., Main Outcome Measures: The duration of CAPD therapy, duration of CAPD training, mortality rate, hospitalization rate, peritonitis rate, and family assessment were reviewed and analyzed., Results: The mean +/- SD duration of therapy was 20 +/- 17 months. Nine patients expired, 3 transferred to hemodialysis, 1 recovered renal function, and 5 remained on CAPD therapy. Peritonitis rates were 1.7 episodes/patient year. Of the organisms causing peritonitis, 56% were gram-positive bacteria. The average hospitalization rate was 13.9 days/patient year. The most frequent causes of hospitalization were peritonitis and cardiovascular disease., Conclusion: CAPD therapy is a reasonable therapeutic option for patients with end-stage renal disease over 80 years of age.

Hyperparathyroidism remains a cause of significant morbidity in dialysis patients. We studied pulse oral calcitriol, 5.0 micrograms biweekly to control hyperparathyroidism in 12 continuous ambulatory peritoneal dialysis (CAPD) patients. Parathyroid hormone (PTH) levels fell, while calcium and phosphorus levels remained in good control. Pulse oral calcitriol is an effective therapy for hyperparathyroidism in CAPD patients.

The optimal way to objectively measure the adequacy of continuous ambulatory peritoneal dialysis (CAPD) therapy remains controversial. It has been suggested that one-third or more of all CAPD patients are presently receiving "inadequate dialysis" when dialysis prescriptions are not carefully calculated. To better define the therapy being delivered in a large, freestanding CAPD center, weekly KT/V urea and creatinine clearance per 1.73 m2 body surface area were measured in 56 of 180 patients randomly selected from our unit in whom dialysis prescriptions were arbitrarily determined by nurses and physicians. In addition, protein catabolic rates and selected clinical outcome criteria were assessed. Weekly KT/V urea correlated with weekly creatinine clearance (r = 0.50) as well as with the protein catabolic rate (r = 0.45). Patients were arbitrarily divided into three groups based on KT/V urea measurements. Thirty percent of the patients had weekly KT/Vs < or = 1.4, 41% had KT/Vs between 1.5 and 1.8, and 29% had weekly KT/Vs > or = 1.9. Significant differences were not noted in hospitalization rates, erythropoietin doses, or serum albumin concentrations in patients with KT/Vs < or = 1.4 and in patients with KT/Vs > or = 1.9. Peritonitis rates were highest in the patients with KT/V > or = 1.9. Therefore, in patients randomly selected from our large CAPD center, 30% of the patients had weekly KT/V urea measurements < or = 1.4. The clinical significance of this finding remains uncertain.

The purpose of this study is to examine the natural history of Pseudomonas aeruginosa exit site infections in continuous ambulatory peritoneal dialysis (CAPD) patients treated with oral ciprofloxacin and local exit site care. A retrospective view was undertaken of 18 episodes of P. aeruginosa exit site infections developing in 17 patients maintained on CAPD during 1989 and 1990. Standardized therapy for the exit site infection consisted of oral ciprofloxacin (500 mg twice daily) and local exit site care with antiseptic agents. Fifteen (83%) of 18 of the pseudomonas exit site infections resolved with therapy. Three episodes (17%) required catheter removal to successfully eradicate the infection. Four of the 15 patients whose exit site infections resolved developed P. aeruginosa peritonitis 2 to 9 months after the clinical resolution of the exit site infection. The majority of pseudomonas exit site infections in CAPD patients can be successfully treated with oral ciprofloxacin and local care. Approximately 17% of the patients in this study required catheter removal to successfully eradicate the infection and an additional 22% of the patients developed pseudomonas peritonitis several months after the resolution of the exit site infection.

In 1989, a conference was held to discuss the current status of technique survival for patients treated with continuous ambulatory peritoneal dialysis (CAPD). Major reasons for patient drop-out from CAPD-peritonitis, inadequate dialysis, catheter-related problems and psychosocial factors-were reviewed, as were constructive techniques for dealing with these problems and areas for future investigation.

This review of adaptive changes in renal structure and function in subjects with reduced renal mass has two primary goals. One is to provide a description of the remarkable compensatory increases in glomerular filtration rate (GFR), and renal blood flow, at the level of individual nephrons, and the alterations in water and electrolyte transport by tubular epithelium. These processes preserve fluid and electrolyte balance in subjects with progressive renal failure, until whole kidney GFR is reduced to about 20 percent of normal, and provide the basis for conservative clinical medical management. The other aim is an attempt to provide an understanding of the mechanisms involved in compensatory adaptation, since this information, in addition to amplifying our understanding of renal transport processes, helps to elucidate the functional limitations placed on subjects with renal insufficiency. An attempt has been made to analyze both clinical observations and relevant experimental models and an effort has been made to correlate renal function with different patterns of renal injury.

The clinical course was reviewed of 102 renal allograft recipients between December 1967 and December 1973. Only 4 of 21 patients (19 per cent) who had 2 or more episodes of rejection during the first 2 months had a functioning graft at the end of 1 year, compared to 24 of 30 patients (83 per cent) who had no rejection episodes. A similar trend was seen 2 to 6 months after transplantation. During the first 2 years vigorous immunosuppressive therapy for rejection in the first few months resulted in 12 deaths (44 per cent) of 27 patients. Subsequent to this immunosuppressive therapy was modified and grafts were removed if there was not a prompt recovery of function after treatment, which resulted in a significant decrease in mortality rate to 16 per cent. There also was improvement in the over-all survival of patients with functioning grafts from 37 to 56 per cent. Serious complications and mortality could be related to high dosage of steroids and severe leukopenia. A white blood count of less than 1,000 m m.3 on 3 successive days was associated with a mortality rate of 52 per cent, compared to 15 per cent in those without leukopenia. Serious consideration should be given to early graft removal in patients who have 2 or more episodes of rejection in the first few months after transplantation, particularly when there is not a prompt improvement in renal function after immunosuppressive therapy. High doses of steroids (greater than 1 mg. per kg. for more than 26 days during the first 60 days) should be avoided to decrease morbidity and mortality rates from serious infections. The results of histocompatibility (HL-A) matching in 72 donor-recipient pairs indicated an improved graft survival when there was a match of 2 or more antigens, which is supported by the results recently reported by the Transplant Registry. The results of mixed lymphocyte reactions in 20 live donor-recipient pairs showed a marked improvement in graft survival when there was less than 20 per cent stimulation and it appeared that this reaction was of more important prognostic significance than the results of histocompatibility (HL-A) matching in these patients.

In 68 consecutive renal transplant biopsies, histopathologic changes and clinical status of the graft recipient, both at the time of biopsy as well as one month later, were evaluated by independent observers. Nine histologic features were graded semiquantitatively (scale, 0 to 4): glomerular endothelial swelling, proliferation, exudation and necrosis; interstitial edema and infiltrate: vascular endothelial edema, infiltration and necrosis. The total score for each biopsy was termed the acute rejection index (ARI). The validity of the ARI as a means of evaluation rejection reactions was established by correlating the ARI with a second, overall histopathologic categorization. Clinical status at the time of biopsy was classified by retrospective analysis of all clinical data except the biopsy. The mean ARI of patients with an acute clinical rejection was significantly higher than those of patients with just a chronic clinical rejection or no clinical rejection. The utility of the biopsy in predicting the response of the graft recipient to therapy was evaluated in those 46 patients in whom an acute rejection was diagnosed clinically and in whom a full and complete course of therapy for the acute clinical rejection was given. Of the 28 patients whom the pathologist predicted would response to therapy, 27 did show substantial improvement of their renal function up to one month following institution of treatment. Of the 18 patients whom the pathologist predicted would not respond to therapy, 15 had no clinical response. The data suggest that the transplant biopsy is helpful in 1) establishing the diagnosis of an acute rejection and 2) indicating whether or not the graft recipient will respond to standard immunosuppressive treatment for an acute rejection,

A retrospective study of the response of the leukocyte count to renal transplant rejection was performed in 159 rejection episodes. Results of the study showed that 1. contrary to what is commonly thought leukocytosis is the least common response to acute rejection and a decrease in leukocyte count is far more common, 2. a sudden decrease in leukocyte count in a previously stable patient can be an early sign of rejection, 3. there is a significantly greater incidence of graft loss in rejection episodes characterized by leukopenia and 4. the risk of infection following rejection is greatest in patients with rejection characterized by leukopenia.

The present study describes our experience with CAPD in an unselected group of patients presenting with endstage renal failure. Twenty-three consecutive patients were offered CAPD, in-center, and home hemodialysis. Twenty-two patients selected CAPD, including 14 patients more than 60 years of age, four patients with diabetes, and one with multiple myeloma. CAPD training was performed in an out-of-hospital office facility. One patient returned to hemodialysis following the development of resistant Pseudomonas peritonitis, two patients died of a myocardial infarction, and one patient died with a GI bleed. The other 18 patients are doing well. Assessment of 17 patients maintained on therapy for four months or more revealed that the patients are less depressed, less organic, and have fewer physical symptoms than previously reported for a comparable group of patients maintained on hemodialysis for a similar period of time. In conclusion, CAPD can be successfully employed, at least for the initial months of therapy, to treat the vast majority of patients with endstage renal disease. CAPD training and follow-up care can be provided in an out-of-hospital office facility.

The treatment of end-stage renal failure was studied in southern Connecticut from 1967 to 1975 by (1) calculating survival rates for center and home dialysis patients and cadaver and living related donor transplant recipients and (2) assessing the quality of life with structured interviews and psychological tests. While the survival rate for our home dialysis and transplant recipients were similar to previously reported data, mortality for our center dialysis patients was slightly higher than previously reported. Quality-of-life testing, disclosed that dialysis patients had a substantial impairment in all parameters. Transplant recipients achieved a better degree of rehabilitation. Physicians and patients should be aware of the problems that they are likely to face; otherwise, expectations and goals may be raised to unreachable and ultimately frustrating levels.

The long-term efficiency of chronic peritoneal dialysis was investigated during a 10-months follow-up period in eight patients with indwelling Tenckhoff catheters by determining sequential urea, creatine and glucose clearances. Dialysis was performed in the hospital with nurses changing commercially prepared 2-liter dialysate bottles. Mean +/- SE urea clearance declined from an initial valua of 23.6 +/- 1.5 ml/min to 17.7 +/- 1.2 at the termination of the study. The mean glucose and creatinine clearance also decreased from 14.1 +/- 0.9 to 10.2 +/- 0.7 and from 17.5 +/- 1.9 to 12.9 +/- 1.0, respectively. All of these decreases were statistically significant (p less than 0.05) by paired t testing analysis. It is concluded that the efficiency of chronic peritoneal dialysis may decline during maintenance therapy and that sequential clearance measurements should be obtained in all chronic peritoneal dialysis patients.

A 25-year-old woman survived a fulminant epidose of rapidly progressive renal failure with severe hemoptysis initially suspected of being Goodpasture's syndrome. Four years later the patient was diagnosed as having Wegener's granulomatosis.

We have studied the effect of intraperitoneal nitroprusside on small (urea) and middle (vitamin B12) molecule dialysis clearances in patients maintained on chronic peritoneal dialysis. Clearances were measured in six patients during the addition of 6 mg of nitroprusside to three and seven consecutive, hourly two-liter exchanges during the course of a routine dialysis treatment. Results indicate that clearances of urea and B12 both increased about 35 percent with the addition of the vasodilator for three exchanges. Clearances immediately returned to baseline values when administration of the vasodilator was discontinued. Addition of the drug to seven consecutive exchanges resulted in a sustained 35 percent increment in clearances. We conclude that addition of 6 mg of nitroprusside to peritoneal dialysis solution can result in a significant increment in both small and middle molecule clearances. Maintenance of the higher clearances requires sustained administration of the drug, which can be tolerated for at least six exchanges with no adverse side effects.

To evaluate the mechanism and role of hyperglucagonemia in the carbohydrate intolerance of uremia, 19 patients with chronic renal failure (12 of whom had undergone chronic hemodialysis for at least 11 mo) and 35 healthy control subjects were studied. Plasma glucagon, glucose, and insulin were measured in the basal state, after glucose ingestion (100 g), after intravenous alanine (0.15 g/kg), and during a 3-h continuous infusion of glucagon (3 ng/kg per min) which in normal subjects, raised plasma glucagon levels into the upper physiological range. Basal concentrations of plasma glucagon, the increment in glucagon after infusion of alanine, and post-glucose glucagon levels were three- to fourfold greater in uremic patients than in controls. The plasma glucagon increments after the infusion of exogenous glucagon were also two- to threefold greater in the uremics. The metabolic clearance rate (MCR) of glucagon in uremics was reduced by 58% as compared to controls. In contrast, the basal systemic delivery rate (BSDR) of glucagon in uremics was not significantly different from controls. Comparison of dialyzed and undialyzed uremics showed no differences with respect to plasma concentrations, MCR, or BSDR of glucagon. However, during the infusion of glucagon, the increments in plasma glucose in undialyzed uremics were three- to fourfold greater than in dialyzed uremics or controls. When the glucagon infusion rate was increased in controls to 6 ng/kg per min to produce increments in plasma glucagon comparable to uremics, the glycemic response remained approximately twofold greater in the undialyzed uremics. The plasma glucose response to glucagon in the uremics showed a direct linear correlation with oral glucose tolerance which was also improved with dialysis. The glucagon infusion resulted in 24% reduction in plasma alanine in uremics but had no effect on alanine levels in controls. It is concluded that (a) hyperglucagonemia in uremia is primarily a result of decreased catabolism rather than hypersecretion of this hormone; (b) sensitivity to the hyperglycemic effect of physiological increments in glucagon is increased in undialyzed uremic patients; and (c) dialysis normalizes the glycemic response to glucagon, possibly accounting thereby for improved glucose tolerance despite persistent hyperglucagonemia. These findings thus provide evidence of decreased hormonal catabolism contributing to a hyperglucagonemic state, and of altered tissue sensitivity contributing to the pathophysiological action of this hormone.

The pharmacokinetics of tobramycin and clindamycin were examined in patients undergoing peritoneal dialysis for chronic renal failure. Peak serum levels of tobramycin in functionally anephric patients were less than expected, probably secondary to a larger volume of distribution. Peritoneal dialysis resulted in a significant clearance of tobramycin, with a resultant reduction in serum half-life. The present data suggest that, if bactericidal serum levels of tobramycin are to be maintained in patients undergoing peritoneal dialysis, a parenteral loading dose be administered, followed by either (i) an identical dose every third half-life or (ii) one-half the loading dose every half-life. However, optimal therapy is best achieved by monitoring serum levels to insure appropriate drug dosage. Peak serum levels of clindamycin in functionally anephric patients were approximately twofold greater than those expected in normals after an identical parenteral dose. It is, therefore, recommended that the administered dose of this agent in functionally anephric patients be one-half of that required to produce desired peak serum levels in patients without renal impairment. Peritoneal clearance of clindamycin during dialysis was shown to be essentially zero, indicating that dialysis does not affect clindamycin disposition.

A total of 22 cases of acute rejection episodes occurring six months to five years after renal transplantation were retrospectively reviewed for the presence of fever, graft tenderness, increase in blood pressure, declining urine output, falling urine sodium level, change in WBC count, and patient's response to antirejection therapy. A total of 13 episodes were not associated with any of these symptoms or signs of an acute rejection episode; seven episodes were associated with an increase in blood pressure alone and only two episodes were associated with fever. Nineteen rejection episodes were confirmed by biopsy. In 16 of these late-rejection episodes, the patient had complete or partial response to therapy. Acute rejection episodes can occur months to years after transplantation; patients are typically asymptomatic; many patients do respond to therapy; and biopsy is often helpful in establishing the diagnosis.

In a population of 214 patients on continuous ambulatory peritoneal dialysis (CAPD), 415 peritoneal infections occurred between 1980 and 1986. Fourteen of these infectious events were caused by Pseudomonas aeruginosa (3.4%). None of those patients with P aeruginosa peritonitis were cured by medical therapy alone. Peritoneal catheter removal was necessary to achieve resolution of the infection. Significant patient morbidity from Pseudomonas infection included loss of peritoneal space for further dialysis and abscess formation. Our data suggests that prompt catheter removal should be seriously considered for chronic ambulatory peritoneal dialysis patients who develop P aeruginosa peritonitis.

The pharmacokinetics of cefamandole nafate, a new parenteral cephalosporin derivative, were evaluated in 11 patients with chronic renal failure (creatinine clearance less than 5 ml/min), including five patients during hemodialysis, four patients during routine peritoneal dialysis, and two patients during the interdialytic period. Peak serum levels of cefamandole were comparable to those observed in patients with normal renal function. Clearance of the drug during the interdialytic period and during hemodialysis and peritoneal dialysis was minimal, with a resultant significant prolongation of serum half-life. The nondialyzability of cefamandole is in contrast with reported studies of cephalothin, where significant reduction of the serum half-life was achieved during hemodialysis but not peritoneal dialysis. The concentration of cefamandole in the peritoneal dialysate after parenteral administration was observed to be bactericidal for many gram-negative pathogens and, with the exception of Streptococcus faecalis, most gram-positive organisms found in bacterial peritonitis in patients with severe renal failure. The present data suggest that if stable bactericidal serum levels of cefamandole are to be maintained during hemodialysis and peritoneal dialysis, a parenteral loading dose must be administered followed by one-half the loading dose every half-life.

We have reviewed our experience with 19 proximal forearm arteriovenous fistulas used in chronic hemodialysis. Thirteen functioned adequately, and of these 10 were complicated by dislodge needles during dialysis, arm edema or hematomas. Although 3 patients developed symptoms of arterial steal, none required ligation of the fistula. This experience suggests that antecubital fossa fistulas might best be used as a second line angioaccess when distal forearm fistulas have been unsuccessful or are impossible to contruct.

To examine the role of the kidney in the mechanism of impaired metabolic clearance of glucagon in renal failure, the renal handling of endogenous pancreatic glucagon was studied in rats with normal renal function and rats with renal insufficiency produced by 70% surgical ablation. Mean +/- SE renal extraction of glucagon in animals with normal renal function was 39 +/- 5%. Urinary losses of glucagon accounted for less than 2% of renal extraction. In contrast, in the animals with renal insufficiency (glomerular filtration rate reduced to one-third of normal), arterial glucagon increased 40% and renal extraction and extraction rate per gram kidney weight of glucagon were negligible, despite filtered loads of 204 +/- 42 pg/min per g kidney wt. These findings indicate a major role of the kidney in the metabolic clearance of glucagon under normal conditions and suggest that during renal insufficiency elevated plasma levels of glucagon occur, at least in part, as a result of a decreased renal turnover of the hormone.

A model for performing peritoneal dialysis in the rat was established which permitted the consistent measurement of dialysis clearances. The effects on urea and inulin clearances of interperitoneal vasodilators and 4.25% dextrose were compared. Isoproterenol, nitroprusside, histamine, and bradykinin, when added to 1.5% dextrose dialysate for three consecutive exchanges, all produced approximately a 20% increase in urea and inulin dialysis clearances. These increases in clearances persisted in the three subsequent exchanges when no drugs were added to the dialysate. The addition of isoproterenol, nitroprusside, or histamine to six consecutive exchanges did not produce a further increment in clearances. The use of 4.25% dextrose dialysate for three exchanges produced approximately a 50% increase in urea and inulin clearances. Clearances remained about 35% greater than control values in the subsequent three 1.5% dextrose exchanges.

In addition to the somatic problems associated with uremia and dialysis it is apparent that successful hemodialysis is dependent upon psychological adjustment to this type of therapy. While previous studies have focused on the patient or spouse as individuals, patterns of marital interactions and conflicts have not been systematically evaluated. These factors ere examined in 17 medically stable patients maintained on hemodialysis for a mean duration of 22 +/- 4 SE months. Standardized pssychiatric evaluation forms ere used to examine mood and cognition disturbances in all patients and spouses, and a deailed marital questionnaire, which each patient and spouse filled out independently, was used to evaluate fundamental aspects of the marital relationship...

This study was designed to (1) develop a simple technique of estimating 'middle-molecule' clearances in peritoneal dialysis patients using vitamin B12 as a marker; (2) evaluate changes in small- and middle-molecule clearances during a single 24- or 36-hour peritoneal dialysis, and (3) determine if using 4.25% rather than 1.5% dextrose exchanges alters the clearances of small and middle molecules. Measurement of clearance following the intramuscular injection of vitamin B12 was found to be a reliable method of estimating the clearance of middle molecules. Small- and middle-molecule clearances remain constant throughout an individual 24- or 36-hour dialysis. In addition, small-molecule clearances increase significantly with 4.25% dextrose dialysate but return to prior values when 1.5% dextrose dialysate is reinstituted.

Renal biopsies were performed on 21 of 27 Melanesian patients presenting with significant proteinuria in Vanuatu from 1983 to 1985. All patients had more than 2 g of proteinuria per 24 hours or clinical evidence of the nephrotic syndrome. The average age of the patients who were biopsied was 31 years. Three of the 21 patients had evidence of active malaria at the time of presentation, and all of these patients had Plasmodium falciparum. Renal histopathology revealed that six patients (29%) had amyloidosis and five patients (24%) had mesangiocapillary glomerulonephritis (type 1). Of particular note was the fact that only one patient had membranous glomerulonephropathy and only one patient had minimal change nephrotic syndrome, the two most common lesions reported in nephrotic patients in Europe and the United States. Thus, the spectrum of renal histopathology in patients presenting in Vanuatu with significant proteinuria is very different from that seen in Western Countries.

Systematic studies of relationships among depression, sexual function, and martial discord in hemodialysis patients and their spouses arelacking; existing studies focus upon only one of these three topics, or deal with patient or spouse as individuals rather than as a couple. We studied 17 chronic, medically stable hemodialysis patients and their husbands or wives. Although couples rated their degree of marital discord as low, the investigators rated it as high, based on the number and type of specific problems reported by the couple. The couples' evaluation may not represent denial, as has been commonly assumed. Instead their evaluation may imply that the disease and its treatment overshadow marital problems, even though couples recognize and react to these problems. Couples showed a high prevalence of sexual problems--in terms of overall satisfaction, frequency of intercourse, and specific dysfunctional symptoms (difficulty becoming excited, maintaining excitement, or having orgasm). We found a strong relationship between severity of depression and severity of sexual dysfunction in patients, but not in their mates. No strong relationship existed between a patient's depression score and marital discord, although spouses showed a trend toward correlation between severity of depression and martial discord. Younger couples, especially, seem not to want intercourse when severe martial discord exists. Patients' depression scores were comparable to thoseof psychiatric patients, while spouses' depression scores resembled those of normals. While psychosocial phenomena such as marital discord, sexual dysfunction, and depression are clear, causal chains are not. Despite disadvantages inherent in using questionnaires, short, self-administered, easily scored instruments may elicit problems with sex, marriage, and mood which might otherwise be overlooked by caretaking personnel.

Acute, reversible renal failure affecting primarily medullary structures, was produced by feeding rats a diet containing 5% oxonic acid and 2.5% uric acid for 7 days. Inulin clearance and selected tubular transport processes were studied and compared to controls. At the time of maximal renal injury, inulin clearance was reduced to 40% of control values, in association with a 60% reduction in urine concentrating ability, a 50% reduction in potassium excretion and a 56% reduction in ammonium excretion. During a 7-day recovery period, inulin clearance increased to 70% of control and potassium excretion returned to normal while the other tubular transport functions remained impaired. Thus, in acute renal failure, tubular functional impairments may recover at different rates.

The pharmacokinetics of digoxin and digitoxin in patients undergoing long-term hemodialysis were examined to determine which is the preferred cardiac glycoside in this patient population. Absorption curves from 0 to 24 hours after an oral dose of digitoxin were similar in dialyzed patients and in control patients. Serum glycoside concentrations after an oral dose of digoxin were higher in dialyzed patients than in control patients, significantly so from 2 to 24 hours, reflecting the absence of the predominantly renal route of excretion of digoxin. When nine dialyzed patients were placed on a maintenance dose of digoxin, 0.125 mg 5 days a week, serum levels plateaued at 30 days at a mean concentration (plus or minus SE) of 0.84 plus or minus 0.05 ng/ml. Maintenance therapy with 0.1 mg digitoxin 5 days a week resulted in stabilization of serum levels within 30 days at a mean concentration of 19 plus or minus 1 ng/ml. Variability in the serum glycoside concentrations was determined after stabilization of levels during 2 to 19 week follow-up periods with each drug. Variability in serum levels was somewhat increased during maintenance therapy with digitoxin. On the basis of the parmacokinetic data obtained in this study, no clear cut preference for one glycoside over the other could be established.

The clinical course was reviewed of 102 renal allograft recipients between December 1967 and December 1973. Only 4 of 21 patients (19 per cent) who had 2 or more episodes of rejection during the first 2 months had a functioning graft at the end of 1 year, compared to 24 of 30 patients (83 per cent) who had no rejection episodes. A similar trend was seen 2 to 6 months after transplantation. During the first 2 years vigorous immunosuppressive therapy for rejection in the first few months resulted in 12 deaths (44 per cent) of 27 patients. Subsequent to this immunosuppressive therapy was modified and grafts were removed if there was not a prompt recovery of function after treatment, which resulted in a significant decrease in mortality rate to 16 per cent. There also was improvement in the over-all survival of patients with functioning grafts from 37 to 56 per cent. Serious complications and mortality could be related to high dosage of steroids and severe leukopenia. A white blood count of less than 1,000 mm.3 on 3 successive days was associated with a mortality rate of 52 per cent, compared to 15 per cent in those without leukopenia. Serious consideration should be given to early graft removal in patients who have 2 or more episodes of rejection in the first few months after transplantation, particularly when there is not a prompt improvement in renal function after immunosuppressive therapy. High doses of steroids (greater than 1 mg. per kg. for more than 26 days during the first 60 days) should be avoided to decrease morbidity and mortality rates from serious infections. The results of histocompatibility (HL-A) matching in 72 donor-recipient pairs indicated an improved graft survival when there was a match of 2 or more antigens, which is supported by the results recently reported by the Transplant Registry. The results of mixed lymphocyte reactions in 20 live donor-recipient pairs showed a marked improvement in graft survival when there was less than 20 per cent stimulation and it appeared that this reaction was of more important prognostic significance than the results of histocompatibility (HL-A) matching in these patients.

The occurrence of acute rejection episodes following renal transplantation was correlated with one-year patient mortality and graft failure rates in a series of 102 consecutive transplant recipients. Twenty-one patients had two or more rejection episodes in the first two months post transplantation; 17 of these expired or lost their kidney compared to only 5 of 28 patients with no rejection episodes in this time period. Similarly, of the 14 patients who developed a second rejection episode 2--6 months post transplantation, 8 died or lost the graft compared to only 2 of 21 patients who had no rejection episodes in this time period. Thus, the development of a second rejection episode early after transplantation necessitating treatment with high dose prednisone therapy carries an ominous prognosis and suggests that serious consideration must be given to graft removal and subsequent retransplantation.