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Background: The diagnosis of myocardial necrosis in patients with chronic renal failure is often difficult because biochemical markers of cardiac damage such as creatine kinase MB (CKMB) and cardiac troponin T (cTnT) may be spuriously elevated. Recent small studies also report unexplained elevations in cardiac troponin I (cTnI) in chronic renal failure patients undergoing hemodialysis. The relative incidence of elevated cardiac troponins in this population and their relationship to clinical events remain unknown., Objective: To determine the incidence and prognostic significance of asymptomatic elevations of cTnT and cTnI in patients undergoing hemodialysis for chronic renal failure., Design: Prospective cohort study., Setting: University tertiary care teaching hospital., Patients: One hundred thirteen patients over 21 years of age undergoing onsite hemodialysis were enrolled between December 1997 and February 1998., Measurements: All-cause and cardiovascular mortality, hospitalization for acute myocardial infarction, unstable angina or congestive heart failure, new onset sustained arrhythmia or need for unscheduled emergency hemodialysis due to volume overload at 30 days and six months., Results: The incidence of abnormal results for cTnT, cTnI and CKMB were 42%, 15% and 4%, respectively. Independent predictors of mortality at six months were median age greater than 63 years (odds ratio 14.3, 95% CI 1.5 to 130.3, P=0.019) and positive cTnT (odds ratio 13.6, 95% CI 2.5 to 73.2, P=0.002). Diabetics were more likely to have positive cTnI and cTnT results than nondiabetics (P<0.001 and P=0.023, respectively)., Conclusions: cTnT is commonly elevated in patients with chronic renal failure even in the absence of acute coronary syndromes. cTnT may be an important independent prognostic marker in patients on hemodialysis for chronic renal failure. While less common, elevations of cTnI are more frequent than CKMB elevations. The basis of these cardiac troponin elevations is unclear. These findings may represent, in part, a subclinical myocardial injury, an inflammatory response to chronic renal failure or a chronically volume overloaded state.

In a regional CAPD program in Northern Alberta, Canada, the peritonitis rates among patients undergoing CAPD treatment were quite high: 1/8.3 and 1/7.4 per patient month from a population of 75 and 76 patients in 1989 and 1990 respectively. Our patient population is comprised of different ethnic groups, separated widely from the dialysis centre; over half of them are above the age of 60 years. As it is not possible to change the patient characteristics in our centre, we switched to the Twin-bag disconnect system in 83 out of a total of 103 patients in 1991. With this change our overall peritonitis rate has significantly improved to 1/14 per patient months and 1/17 per patient months in patients using the Twin-bag system. This improvement in the peritonitis rate has occurred without any change in our patient characteristics. We find the improvement in our peritonitis rate is due to the use of the new Twin-bag system, which provides total disconnection with no spikes and thereby reduces peritonitis due to touch contamination.

Cyclosporin A (CyA) is a powerful immunosuppressive agent whose lack of myelotoxicity makes it unique among nonsteroidal drugs currently given for immunosuppression. It has been used with initial success in recipients of kidney, liver, bone marrow and pancreas transplants, and it may also have clinical application in the treatment of autoimmune disorders. In regard to its use in transplant recipients, there are many remaining questions about its mechanism of action, the optimum dose, whether it should be used alone or with other immunosuppressants, whether it can suppress chronic rejection and what its long-term side effects may be. These questions can only be answered by further careful laboratory investigation and controlled clinical trials. Until then, CyA should only be administered in centres experienced in its use.

We assessed various immune responses against donor tissue to determine their value in the diagnosis and prediction of clinical rejection episodes. Twenty-six consecutive clinical renal-transplant recipients were examined. Cell-mediated lymphocytotoxicity preceded and accompanied 41 of 45 rejection episodes (P less than 0.001). Complement-dependent antibody was present in 12 of 15 rejections (P less than 0.002)--four not accompanied by, and eight in association with, cell-mediated lymphocytotoxicity. Mixed lymphocyte reactivity or nonreactivity and inhibition by autologous serum occurred equally often in rejection and quiescence. Lymphocyte-dependent antibody occurred during both rejection episodes and quiescent phases, with a greater frequency during quiescence (P = 0.05). Cell-mediated lymphocytotoxicity was the best predictor of rejection (P less than 0.05). Cell-mediated lymphocytotoxicity was the best predictor of rejection (P less than 0.001), and was more easily suppressed by standard immunosuppressive therapy, than complement-dependent antibody. If specific cell-mediated lymphocytotoxicity, with or without antibody, recurred after rejection therapy, the graft underwent further rejection.

We have previously reported that treatment of uremia by hypertonic hemodiafiltration (H-HDF) results in a more stable hemodynamic response as compared to standard hemodialysis (HD). The purpose of this study was to determine if plasma volume (PV) preservation was a significant factor in this response. Nine patients were studied during single treatment sessions of H-HDF and HD. Both sessions were 3 h in duration and the ultrafiltration rate and volume were matched. 10 microCi of 125I human serum albumin were injected 40 min before each session for measurement of PV. Changes in PV during the session were determined from the change in plasma albumin concentration and the hematocrit. The decrease in PV was significantly less during H-HDF. This was associated with a significantly higher plasma sodium and osmolality. The calculated effective osmolality during H-HDF was not only higher than in HD, but showed a significant increase at 2 and 3 h when compared to the baseline level (p less than 0.05). The calculated volume of extravascular mobilization was higher during H-HDF and is probably the mechanism of the PV preservation. In conclusion, this study demonstrates that PV is preserved during H-HDF better than during HD as a result of a more adequate plasma refilling; this appears to be mediated by an increased plasma effective osmolality.

In 56 patients 1-year renal-graft survival was significantly better (71% vs 40%) in those who had received blood before operation, confirming previous observations. In addition, transfusion on the day of operation proved to have been beneficial, both in those previously transfused (82% vs 64%) and in those never previously transfused (71% vs 28%). Irrespective of pretransplant transfusion, 1-year graft survival was significantly better (79% vs 44%) in those transfused on the day of operation.

Eight patients who met the clinical, immunological and renal morphologic criteria for systemic lupus erythematosus with diffuse proliferative nephritis were plasma exchanged on a monthly basis for a total of 119 months. Renal function, episodes of disease activity, hospitalizations, frequency of immunological abnormalities, and monthly quantity of steroid and azathioprine therapy were compared with their course up to one year prior to the onset of the plasma exchange program. The changes noted in these parameters indicate that chronic plasma exchange therapy is safe, may be beneficial and requires controlled prospective study to determine the role in the treatment of patients with systemic lupus erythematosus and diffuse proliferative glomerulonephritis.

Cerebral edema in uremic animals and humans, as well as an EEG deterioration in humans, has been reported after dialysis. Both are manifestations of the dialysis disequilibrium syndrome (DDS). This study was designed to analyze the changes induced by dialysis in the EEG pattern (spectral analysis), in the cerebral hydration, and ventricular size (computed tomography [CT] of the brain) in a group of 11 stable uremic patients. They volunteered for a randomized crossover study of 4 months each of standard hemodialysis (HD) and hypertonic hemodiafiltration (H HDF). H HDF is a dialysis technique that is shorter and more efficient than HD. An EEG recording, a CT scan of the brain, and blood biochemistry were performed before and after a HD (four hours, blood flow rate 250 mL/min) and a H HDF run (three hours, blood flow rate 400 mL/min). Approximately 6 weeks of stabilization on each treatment were allowed before these studies. No difference was found in the density of seven specific brain structures (base and apical cuts), when comparing pre- v post-HD, pre- v post-H HDF, pre- HD v pre-H HDF, and post-HD v post-H HDF. Furthermore, no difference was evident either in the bicaudate diameter of the lateral ventricles or in the transverse diameter of the third ventricle. In addition, no significant in-between- and within-treatment difference was observed when analyzing the EEG% power (3-7/7-13 Hz) data. In conclusion, this study shows neither a postdialysis change in brain density and ventricular size nor a postdialysis EEG deterioration in a group of stable uremic patients undergoing both a rapid and a standard dialysis treatment.(ABSTRACT TRUNCATED AT 250 WORDS)

We have developed an extracorporeal system for investigating in vitro the biofilm-adherent bacterial microcolonies (BABM) that grow on Tenckhoff catheters (TC), to study peritonitis in patients undergoing continuous ambulatory peritoneal dialysis (CAPD). A modified Robbins' device, attached to sampling plugs with TC discs and connected to the dialysate via a peristaltic pump, is run for 24 h; scrapings from pairs of TC discs are processed for assessment of viable BABM, one of each pair for culture by routine microbiology techniques and the other for examination by scanning and transmission electron microscopy (EM). No colonization was noted with fresh dialysis solutions and spent dialysates from patients without clinical peritonits; but, when bacterial suspensions were added to aliquots of the same dialysates, BABM were noted on both culture and EM. In a study of 4 patients on CAPD treatment, who had clinically evident peritonitis, routine cultures of spent dialysate were positive in only 2, but BABM were found in cultures and EM preparations of disc scrapings in all 4 cases. We conclude from these preliminary findings that this extracorporeal system is reliable, and well suited for studying the role of BABM in CAPD-associated peritonitis in vitro.

Percutaneous transluminal angioplasty has been applied to the treatment of transplant renal artery stenosis in 3 patients, 2 with severe hypertension resistant to medical therapy, and one with graft dysfunction related to the presence of the stenosis in the early post-transplant period. The clinical courses of the patients before and after angioplasty are illustrated and the usefulness of the technique in this difficult situation stressed.

A 34-year-old woman presented with postpartum renal cortical necrosis. Contrast-enhanced computerized tomography (CT) of her kidneys showed a narrow subcapsular band of increased density that was separated from the medulla by a distinct band of decreased density. This is analogous to the decreased cortical nephrogram seen on arteriography. The CT scan may be a useful, non-invasive diagnostic procedure in renal cortical necrosis.

The association between anemia and chronic renal failure has been recognized since the early 19th century. With the introduction of regular dialysis treatment, an understanding of all aspects of this uremic complication has become of great importance, including an appreciation of the hazards of multiple blood transfusions. This analysis of hemoglobin levels and transfusion requirements in 84 dialysis patients focuses specific attention on hemolytic mechanisms, blood loss, and the effect of bilateral nephrectomy on erythropoiesis. Because no replacement for renal erythropoietin is available, particular attention must be paid to less important, but partially correctable factors that contribute to anemia. Blood transfusion requirements can then be reduced to a minimum, together with the risks of hypersplenism, hepatitis, and sensitization of the patient to alloantigens.

The first reported case of rupture of the renal pelvis associated with transplantation is presented. The obstruction was in the ureteral tunnel of the hypertrophic bladder. The cause of the weakness in the pelvic wall could not be determined. Differential diagnosis was acute rejection and lymphocele. Excretory urography was diagnostic. Treatment included revision of the ureteroneocystostomy with repair of the defect and internal stenting. Postoperative morbidity was minimal and satisfactory graft function was maintained.

Morphometric studies were carried out on teeth extracted from normal human patients and compared with those extracted from patients suffering from chronic renal failure and patients being treated by chronic hemodialysis. The findings revealed that the predentin layer in patients suffering from chronic renal failure and patients undergoing chronic hemodialysis was significantly thicker than normal. These findings suggest that predentin is the metabolic equivalent of osteoid in bone and that increases in the predentin thickness may therefore be a reliable indicator of osteomalacia. It is suggested that the term odontomalacia be used to describe the changes occurring in the dentin of these patients.

A patient with preformed cytotoxic lymphocyte-dependent antibody (L.D.A.) against the specific renal transplant donor rapidly rejected the grafted kidney. The characteristics of rejection were not those of hyperacute rejection due to cytotoxic complement-dependent antibody or of acute rejection is attributed to the cytotoxic activity of L.D.A. The avoidance of transplants based on positive crossmatches by the L.D.A. test or at least the carrying out of the L.D.A. crossmatch is advised.

This study compared the acute and chronic effects on cardiac function of treatment with hypertonic hemodiafiltration (H HDF) and hemodialysis (HD). Cardiac function was assessed before, during and after a run of H HDF and HD using echocardiography and impedance cardiography in 10 patients in a randomized cross-over sequence, two months after stabilization on each treatment. Blood biochemistry was performed before and after each run. Ejection fraction and fractional shortening were significantly higher before the H HDF run, compared to the HD run, and this difference persisted during and after the treatment runs (both P less than 0.05). There was a corresponding significant difference in the increase of the velocity of circumferential fiber shortening and in the reduction of end systolic diameter during and after H HDF (P less than 0.05). Heart rate, stroke volume, cardiac output, systemic vascular resistance and mean arterial pressure did not differ significantly between the two treatments. Plasma calcium and bicarbonate were significantly higher (P less than 0.03) at the start of H HDF and this difference was enhanced at the end of the run. In conclusion, H HDF compared with HD, is associated with a better myocardial function in both the short and long term treatments. The evidence suggests that this may be due to improved levels of plasma calcium, bicarbonate, and/or the removal of an as yet unidentified myocardial toxin.

Screening for urinary tract infection was carried out in 23,427 schoolgirls, aged 5 to 14 years, using Uricult and, for hematuria, glycosuria and proteinuria using Hema-combistix. Cultures of 10(5) colonies per ml. or more on two occasions were obtained in 2.3% and a positive culture was confirmed by the family physician using standard culture techniques in 82.7% of cases, giving an overall incidence of infection of 1.9%. Fifty-eight percent of these children had no previous history of any urinary tract symptoms. Of the infected group 9.5% had pyelonephritic scarring, 58.7% chronic cystitis and 58.7% urethral stenosis. Two additional cases had unilateral ureteropelvic junction obstruction with hydronephrosis. Reflux occurred in 26.6% of those investigated by voiding cystogram. In 58% of cases the urinary tract infection was not accompanied by significant proteinuria, hematuria or pyuria.Proteinuria was detected on two occasions in 1.6% of the children and confirmed by the family physician in 33% of cases, giving an overall incidence of 0.5%. In this group 9.2% had evidence of pyelonephritic scarring without a positive urine culture.Hematuria was detected on two occasions in 0.6% of the children and was confirmed by the family physician in 53%, giving an overall incidence of 0.3%. Only one case with pyelonephritic scarring was seen in this group.Of the 25 cases with pyelonephritic changes only six had been previously diagnosed radiologically.Four previously unrecognized diabetics were also detected.

Immunological reactivity to donor antigens and serum concentrations of cyclosporin A were monitored in six patients after renal transplantation. At concentrations of 0.1--1.0 microgram/ml cyclosporin A prevented both donor-specific immune reactivity and clinical rejection during the early post-transplant course. Measurement of cyclosporin A levels and immunological indices allowed individual adjustment of the dosage so as to give excellent early graft function with few adverse effects.

Immune responses, specific to the stored donor tissue, were measured in 26 recipients over 4,000 days. CML positive crossmatches were associated with accelerated rejections (three cases). LDA positive crossmatches resulted in primary non-functioning kidneys (three cases). Post-transplantation. CML (16 hour inculation) was associated with rejection (p equals 0.001), highly predictive of rejection (p equals 0.001), and when positive after rejection treatment, was associated with a failure to respond (p equals 0.005 - 0.01). 51Cr-CDA was also associated with rejection (p equals 0.002). Recovery of these immunologic participants from the explanted kidney substantiated that they were important effector mechanisms in vivo.

Six cases of edema, three due to the nephrotic syndrome, one to congestive heart failure and two to chronic renal failure, are reported in which furosemide was administered in oral doses higher than those usually prescribed (up to 720 mg. a day), in order to obtain a satisfactory diuresis. In one case of severe prerenal failure secondary to cardiogenic shock and in one case of acute tubular necrosis secondary to hypotension at the time of operation, intravenous doses up to 990 and 1400 mg. per day respectively were able to reverse the oliguria. In eight additional patients who were on chronic hemodialysis, furosemide was administered to the amount of 1000 mg. per day orally in divided doses for two weeks, and produced a moderate diuretic response.The use of high doses of furosemide in edema and renal failure resistant to the usual therapeutic measures appears to be safe and effective.

Thyroid function was studied in 54 patients undergoing chronic hemodialysis. Serum thyroxine, triiodothyronine and free thyroxine and the free thyroxine index were significantly lower than normal. The levels of both serum thyroxine and the free thyroxine index tended to fall progressively the longer the patients were on hemodialysis. These findings, in association with low serum TSH levels and normal increase in radioactive iodine uptake by the thyroid after TSH injection, suggest that a defect in pituitary secretion of TSH may be responsible. Although some patients experienced symptomatic improvement after treatment with L-thyroxine the efficacy of this form of treatment in patients on chronic hemodialysis has not yet been established.