Chlorinated urban water: a cause of dialysis-induced hemolytic anemia.

Unexplained acute hemolytic anemia is sometimes seen in uremic patients undergoing hemodialysis. Chloramines, which are oxidant compounds made up of chlorine and ammonia and are widely used as bactericidal agents in urban water supplies, have been found responsible for two recent epidemics, in dialyzed uremic patients, of acute hemolytic anemia characterized by Heinz bodies. Chloramines produce denaturation of hemoglobin, both by their direct oxidizing capacity and their ability to inhibit red cell reductive (hexose monophosphate shunt) metabolism.

Age, sex, and race inequality in renal transplantation.

We calculated the chance of receiving a kidney transplant in the United States in 1983, and in the Midwest from 1979 through 1985, considering age, sex, and race. In the United States, 23,026 patients began long-term dialysis and 6112 (27%) received a kidney transplant. Transplant rates were 31% for men and 21% for women. White patients had a 30% rate and nonwhite patients a 20% rate. Patients less than 11 to 35 years old had an 85% rate vs a 3% rate for those older than 56 years. When race, age, and sex were analyzed together, nonwhite patients aged 21 to 45 years had only half the chance of receiving a transplant compared with white patients of the same age and sex. Women aged 46 to 60 years had less than half the chance of receiving a transplant when compared with men of the same age and race. These data show that there are age, sex, and race imbalances in the distribution of renal transplantation. We believe these imbalances only partially have a morally neutral biological, medical, social, and cultural explanation and that there should be a fairer distribution of kidney transplants.

Long-term follow-up of 369 diabetic patients undergoing dialysis.

We studied the long-term outcome (after four years) in 233 patients with type I and 136 with type II diabetes mellitus treated with long-term dialysis between 1966 and 1982. The seven-year cumulative survival improved from 12% before 1976 to 20% after 1976. Sixty-eight of the patients survived for more than four years, and 25 are still alive. Of deaths, 51% were due to cardiovascular disease, 24% to the discontinuation of dialysis, 14% to infections, and 11% to other causes. Over the course of the study, older and sicker patients were increasingly accepted for dialysis, and younger and healthier patients were increasingly accepted for transplantation. The 25 patients who are still alive and undergoing dialysis were hospitalized 1.4 times per patient year for 19 hospital days per patient year the first year and for eight days per patient year after that. Two became blind, three had amputations, seven worked full-time. The results of long-term dialysis in patients with diabetes have improved greatly over the last two decades.

Adult hemolytic-uremic syndrome. A review of 37 cases.

BACKGROUND: Adult hemolytic-uremic syndrome is a serious, poorly understood disease with a high and variable mortality. We studied several demographic, clinical, and treatment variables, related them to outcome, and developed a new classification. METHODS: We analyzed data from 37 patients admitted from 1981 to 1991 who fulfilled four criteria (age > 16 years, microangiopathic hemolytic anemia, creatinine level > 150 mumol/L [> 1.7 mg/dL], and no artificial heart valve). Three outcome variables were studied (survival vs death, recurrence vs no recurrence, and chronic renal failure vs no chronic renal failure). RESULTS: Eleven (30%) of the patients died, 10 (27%) needed dialysis, five (14%) developed chronic renal failure, and nine (24%) had recurrent episodes. Patients who presented with colitis did not die or have recurrences, but they developed chronic renal failure as often as other patients. Patients with hemolytic-uremic syndrome secondary to other diseases had the worst survival and the most recurrences. Those without any triggering factor (primary cases) were in between. In multivariate analysis, hemolytic-uremic syndrome secondary to colitis, a higher white blood cell count at admission, and a high maximum mean arterial pressure were associated with good survival prognosis. CONCLUSIONS: The persistence of the trigger of adult hemolytic-uremic syndrome sets the stage for outcome. If the trigger is transient (such as Escherichia coli colitis), the disease will not recur and is rarely lethal. If no trigger is apparent (primary hemolytic-uremic syndrome) or the trigger persists (systemic lupus erythematosus and cancer), the syndrome has a high mortality and often recurs. We suggest a new classification: (1) extrinsic hemolytic-uremic syndrome: (a) toxic, (b) infectious; (2) intrinsic hemolytic-uremic syndrome: (a) primary, (b) secondary. The use of this classification, combined with simple data obtained at presentation and a further division of the cause as transient or persistent and irreversible, may improve the selection of therapy.

A prospective study of risk factors and decision making in discontinuation of dialysis.

BACKGROUND: Discontinuation of dialysis is a common cause of death. We performed a prospective study to determine if a detailed description of patients could be used to identify those at risk for discontinuing dialysis. METHODS: Two hundred thirty-five dialysis patients were studied for 3 1/2 years. Using questionnaires, medical chart analyses, and interviews, 300 sociodemographic, quality-of-life, medical and dialysis variables were prospectively obtained. The association of these variables with death from discontinuation of dialysis was studied in univariate and multivariate analyses. RESULTS: Seventy-six patients (32%) died during the follow-up period, 31 (41%) of cardiovascular problems, 13 (17%) of discontinuation of dialysis, and 32(42%) of other causes. Patients who discontinued dialysis were older (mean age, 66 vs 54 years), were more likely to be divorced or widowed (46% vs 16%), were more likely to live in nursing homes (31% vs 6%), spent less time outdoors (23% vs 53%), had twice as much comorbidity as other patients (major comorbidity score, 1.2 vs 0.6), had the same psychological quality-of-life score (60 vs 62) but a lower score on the Karnovsky Scale, and a higher physical discomfort index. In multivariate analysis, comorbidity, widowed or divorced status, and severe pain were independent predictors of discontinuation of dialysis, but no reliable predictive model could be created. A detailed analysis of the final event indicated that a relentless succession of problems often led nursing home patients to discontinue dialysis. These problems are common to all dialysis patients, especially those who have no one to support them in their suffering. CONCLUSIONS: Discontinuation of dialysis is common, and can been seen as a failure of and a relief from long-term dialysis. We believe mortality caused by discontinuation of dialysis could be decreased by better psychological support and improved management of ischemic problems and pain. We found no predictable model for such patients, but many successive acute problems in widowed and divorced patients seem to trigger the decision.

Mannitol intoxication in patients with renal failure.

Eight patients with severe mannitol intoxication were treated during the last ten years. These patients had CNS involvement out of proportion to uremia, severe hyponatremia, a large osmolality gap (high measured minus calculated serum osmolality), and fluid overload. Six patients were treated with hemodialysis and one patient received peritoneal dialysis. One patient died before any treatment could be started. Mannitol had a half-life of approximately 36 hours during the intervals without treatment. The ideal treatment is hemodialysis that rapidly removes mannitol (half-life, six hours) and replaces it with sodium; peritoneal dialysis removed mannitol slowly (half-life, 21 hours).

Dialysis discontinuation. A 'good' death?

BACKGROUND: Approximately 10% of the deaths of patients receiving long-term dialysis for end-stage renal disease are preceded by discontinuation of dialysis. We prospectively studied the decision to discontinue dialysis and whether, as is often stated, these patients have a prompt, predictable, and comfortable death. METHODS: All patients receiving hemodialysis in a hospital-based and a freestanding unit whose long-term dialysis was discontinued in 1990 were included in the study. Patients, providers, and families of prospectively enrolled cases were interviewed to determine the reasons for discontinuation; the patients' terminal courses were reviewed daily to collect information describing their quality of death. Retrospectively enrolled cases were studied by chart review and interviews of providers. The reasons for discontinuation of dialysis and a rating of the quality of their deaths (for prospectively studied patients only) were determined by interdisciplinary team consensus. Quality of death was rated on scales of 1 (worst) to 5 (best) according to duration of dying, discomfort, and psychosocial circumstances. RESULTS: Eighteen patients discontinued dialysis after a mean duration of 43.6 months of hemodialysis, and they lived a mean of 9.6 days after termination. The quality of death of the 11 patients who were enrolled prospectively was subjectively assessed as "good" (> 10 of a possible 15 points) for seven patients and "poor" for four patients. A good quality of death was more likely if dialysis was discontinued because of medical deterioration from progressive chronic disease (P = .009); none of the three patients whose dialysis was discontinued for other reasons had a good death (P = .024). CONCLUSIONS: A majority of the prospective cohort of patients who discontinued dialysis experienced a good death by our largely subjective criteria. Improved palliative therapy for some of these dying patients, however, could have ameliorated prolonged suffering, delirium, and inadequately treated pain that led to a poor quality of death.

Psychological, social, and somatic prognostic indicators in old patients undergoing long-term dialysis.

We prospectively studied the influence of 29 demographic, social, psychological, and somatic factors on survival of 78 patients over age 70 years receiving long-term dialysis. Three years after the prospective evaluation, 54% of the patients had died. Only four factors, all psychosocial, were prognostically important. The patients who survived rated higher on the Karnofsky scale (85 vs 78 points), gained less weight between dialyses (1.5 vs 1.9 kg), more often underwent home dialysis (44% vs 21%), and less often wished for transplantation (28% vs 57%). In stepwise and multiple regression analysis, home dialysis and Karnofsky scale resulted in best fit. No somatic variable predicted outcome. Thirty-one patients were reinterviewed three years later. At that time, more patients were depressed and had a lower income, fewer wanted a transplant, and five had lost their living companion. There was a decrease in the number of patients who cooked their own meals, spent time outdoors, went to church, or had hobbies. Activity on the Karnofsky scale decreased from 87 to 84 points. The home dialysis patients' perceived health decreased from 3.9 to 3.4 points. Our study shows that psychosocial, but not somatic variables, are prognostically important in survival of older patients undergoing dialysis, and there is a measurable decline in these variables during a three-year follow-up period.

Hemodialysis in diabetics: complications in insulin-dependent patients accepted for renal transplantation.

The hemodialysis complications in 67 insulin-dependent diabetic patients accepted for renal transplantation were compared with those in 67 nondiabetic hemodialysis patients. Eleven of the 67 diabetic patients died before receiving a renal transplant-four of myocardial infarction, three of dialysis-related causes, and four of infections. One of the 67 nondiabetic patients died of infection before transplantation. The diabetic patients experienced more complications on dialysis than did the nondiabetic patients; they were more hypertensive and required more ultrafiltration during dialysis. In addition, the diabetic patients had a higher incidence of hypertensive episodes during dialysis, as well as a high incidence of predialysis hyperglycemia. These findings suggest that diabetic patients with renal failure should be dialyzed more frequently and transplanted as soon as possible in order to decrease the complications associated with hemodialysis.

Dialysis symptoms and stabilization in long-term dialysis. Practical application of the CUSUM plot.

Six symptoms that occur during hemodialysis were investigated to determine their frequency and to define when a patient's condition becomes "stable." Three symptoms--nausea, hypotension, and muscle cramps--stabilized after 13 dialysis treatments (approximately one month). Two symptoms, hypertension and vomiting, stabilized after 17 and 20 dialyses, respectively. Headache showed little variation per dialysis. The changes in the frequency of these symptoms were detected through the use of the cumulative sum technique (CUSUM). This technique was found to be much more discriminating than the original data. Hemodialysis patients should not be considered "stable" for investigation of changes in techniques or therapy until after 1 1/2 months of dialysis. Even then, symptoms will be found during each dialysis.

Severe hypokalemia induced by hemodialysis.

During dialysis, it is assumed that the serum electrolyte levels asymptotically approach the concentration in the dialysate. In five patients, we observed an average 20% fall in serum potassium level, although the dialysate contained 42% more potassium than the predialysis serum. One patient had quadriplegia and near respiratory arrest as a complication of hypokalemia. The cause of the hypokalemia was a rapid shift of potassium from the extracellular to the intracellular space secondary to correction of acidosis. All patients entered dialysis with a history suggesting prolonged potassium loss, marked acidosis, and moderate hypokalemia; thus, the dialysate potassium concentration should be higher than normal, and frequent determinations of the serum potassium level should be performed. Therapy resulting in rapid correction of acidosis in uremic patients undergoing hemodialysis may cause large transcompartmental shifts of potassium. Potassium transfer across the dialysis membrane may be inadequate to compensate for such shifts, and life-threatening hypokalemia may occur.

Long-term dialysis and renal transplantation in lymphatic leukemia.

With increasing experience and skill with renal transplantation and dialysis, many disorders that were previously thought to contraindicate these procedures are no longer regarded as contraindications. We have previously reported that transplantation can successfully be performed in patients who have had malignant diseases if they seem to be cured after approximately 12 months. Although incurable malignancies have usually been regarded as absolute contraindications, successful dialysis and transplantation have been achieved in a patient with chronic lymphatic leukemia.

Dying well after discontinuing the life-support treatment of dialysis.

BACKGROUND: Cessation of life-prolonging treatments precedes death in an increasing number of cases, but little attention has been accorded to the quality of dying. OBJECTIVE: To examine the quality of dying following dialysis termination. PATIENTS AND METHODS: A prospective cohort, observational study involved 6 dialysis clinics in the United States and 2 clinics in Canada, and 131 adult patients receiving maintenance dialysis who died after treatment cessation. Sixty percent (n = 79) underwent patient (n = 23) and/or family (n = 76) interviews and follow-up with caretakers. A quality of dying tool quantified duration, pain and suffering, and psychosocial factors. RESULTS: The sample was 59% female, the age was 70.0+/-1.2 years old, the duration of dialysis was 34.0+/-2.8 months, and death occurred 8.2+/-0.7 days after the last dialysis treatment. (Data are given as mean +/- SE.) Thirty-eight percent of the subjects who completed the protocol were judged to have had very good deaths, 47% had good deaths, and 15% had bad deaths. During the last day of life, 81% of the sample did not suffer, although 42% had some pain and an additional 5% had severe pain. According to the psychosocial domain of the quality of dying measure, patients who died at home or with hospice care had better deaths than those who died in a hospital or nursing home. CONCLUSIONS: Most deaths following withdrawal of dialysis were good or very good. The influence of site of death and physician attitudes about decisions to stop life support deserves more research attention. Quality of dying tools can be used to establish benchmarks for the provision of terminal care.

Phosphorus-enriched hemodialysis for the treatment of patients with severe methanol intoxication.

Severe methanol poisoning requires treatment with prolonged and intensive hemodialytic therapy. Such treatment can engender either the de novo development of hypophosphatemia or the worsening of pre-existing hypophosphatemia. Phosphorus-enriched hemodialysis therapy can prevent the occurrence of this complication. We report three patients with severe methanol poisoning who were treated with phosphorus-enriched hemodialysis. Prevention or treatment of hypophosphatemia was successfully achieved with this dialytic technique.

Hemodialysis in an infant with propoxyphene intoxication.

A 10-month-old infant was treated with intensive supportive care and hemodialysis for severe propoxyphene intoxication. Dialysis clearance studies demonstrated that propoxyphene was removed from the serum at approximately 50% of the rate of blood urea nitrogen removal. Possibly because of tissue binding of the drug, the absolute quantity of propoxyphene removed by dialysis was small. The child survived the acute episode of intoxication but died of pulmonary complications several days later. The role of dialysis in propoxyphene intoxication remains to be established.

Exacerbation of diabetic renal failure following intravenous pyelography.

Twenty-two of 29 (76 per cent) diabetic patients with a creatinine level of more than 2 mg/100 ml had exacerbation of renal failure following intravenous pyelography. In nine patients this was irreversible. Particularly at risk seem to be patients with early onset diabetes (less than 40 years), and those patients with severe renal failure (creatine over 5 mg/100 ml). No less that 15 of 16 (93 per cent) such patients had problems after intravenous pyelography; of these, nine (56 per cent) had irreversible deterioration. This report, in context with the increasing number of case reports of similar findin.gs, indicates that intravenous pyelography is dangerous in patients with juvenile onset diabetes who have a creatinine level of more than 5 mg/100 ml.

Successful renal transplantation in patients with prior history of malignancy.

Eleven selected patients with a history of cancer have received renal transplants. In three patients the malignancies were diagnosed and treated before renal failure developed. Two patients underwent bilateral nephrectomies for the treatment of bilateral renal malignancy. In six patients the malignancy developed while they were uremic, and they received transplants after treatment of the tumor. Recurrent tumor developed in only one of the 11 (9 per cent) patients after receiving the transplant. Thus, patients with a history of malignancy can receive a transplant without accelerating growth of the tumor. We recommend a minimum period of one year between tumor treatment and transplantation to observe for tumor recurrences or metastases. A longer period of observation may be necessary in patients who have tumors with a poorer prognosis.

Etiology and prognosis in acute post-transplant renal failure.

During the last seven years we encountered 117 cases of acute renal failure after 492 renal transplants. The affected patients fall into two general groups that can be broadly identified by an 131I-Hippuran renogram: Those in whom low or no uptake is evident on the renogram (group 1) and those in whom good uptake is evident on the renogram (group 2). Fifty per cent of the patients in group 1 have renal arterial thrombosis or hyperacute rejection. These patients should have a renal arteriogram, and immediate nephrectomy may be necessary. The prognosis in these patients is very grave. In group 2, 89 per cent of the patients have acute tubular necrosis, and they do not differ prognostically from patients who experience immediate renal function. Invasive diagnostic procedures should be avoided in this group because they may increase the mortality rate. We believe that repeated renograms, a reduction in azathioprine dosage and careful dialysis is the only treatment necessary.

115 patients with first cadaver kidney transplants followed two to seven and a half years. A multifactorial analysis.

One hundred fifteen consecutive patients received first transplants from cadaver donors at the University of Minnesota between January 1, 1968, and May 31, 1973. All patients have been followed for at least two years. The two-year survival rate is 70 per cent and the two-year transplant function rate is 58 per cent. Considerable improvement in both patient survival and transplant function has been noted since 1971. The success of transplantation appears to depend to a large degree on the age of the transplant recipient, the number of HLA antigens matched between donor and recipient, and the dose of antilymphoblast globulin (ALG) administered to the recipient during the first two weeks after transplantation. Each of these factors appears to be important even when the other factors are controlled, and when patients with diabetes, suffering technical failure or hyperacute rejection, are excluded. The results utilizing well-matched cadaver kidneys plus large doses of ALG appear to be equivalent to those obtained with the use of mismatched kidneys from relatives, but further analysis will be required to draw a definite conclusion. Patients receiving poorly-matched cadaver kidneys do far less well than patients receiving mismatched related grafts, however, even when ALG is utilized.

Acute tubular necrosis after renal transplantation.

We evaluated the influence of dialysis requiring acute tubular necrosis on patient survival, and kidney survival and function in all 182 patients who needed dialysis immediately after transplantation at the University of Minnesota Hospitals. When compared to matched control patients not requiring dialysis, there was no difference at any point in patient survival. At 1 month there were more kidneys lost in the patients who developed acute tubular necrosis, but this difference was not present at 3 months or later. Acute tubular necrosis is a relatively innocent complication of renal transplantation and, if one avoids assaulting patients with invasive diagnostic procedures, does not give rise to an increased mortality nor, in the long run, to an increased loss of kidneys. Therefore, kidneys should not be discarded because of fear they might develop this complication.