The impact of co-morbid risk factors at the start of dialysis upon the survival of ESRD patients.

By using a computerized database, we have catalogued the presence of 29 co-morbid risk factors in 683 patients with end-stage renal disease who started dialysis from 1970 through 1989, with follow-up through 1992. The authors hypothesized that current end-stage renal disease patients have more serious co-morbid risk factors impacting upon their mortality rate. Quantitation of dialysis patient co-morbidity, as a measure of patient illness, is lacking in the general nephrology literature. Seven co-morbid risk factors have been reserved for new dialysis patients: hypertension, low albumin, cerebral vascular disease, peripheral vascular disease, pre-existing cardiac disease, abnormal EKG/old myocardial infarction, and congestive heart failure. Except for low serum albumin, the proportion of patients with the six other co-morbid risk factors has increased significantly over this 20-year period (p < 0.0001, chi-square test for hypertension, peripheral vascular disease, pre-existing cardiac disease, abnormal EKG/old myocardial infarction, and congestive heart failure, and p < 0.006 for cerebral vascular disease). In addition, the co-morbid risk factors of hypertension, low serum albumin, and pre-existing cardiac disease at the start of dialysis were strongly prognostic of survival. The Cox proportional hazards regression model identified these three risks, among other factors, that were significantly associated with a decreased survival, with risk ratios ranging from 1.40-1.66. These results support the authors' hypothesis that incoming end-stage renal disease patients, who recently start dialysis, are sicker than in the earlier years of the authors' program. If the authors' patients reflect the national end-stage renal disease population, the presence of co-morbid risk factors may, in part, explain the continuing high mortality of dialysis patients.

Home hemodialysis: patient outcomes during a 24-year period of time from 1970 through 1993.

In the United States, from 1983 to 1993, home hemodialysis use has decreased from 6% to 1.3% of the dialysis population, whereas continuous ambulatory peritoneal dialysis (CAPD) has increased to 20%. Most home hemodialysis programs have withered away because of current patient mix, increase in CAPD, proliferation of outpatient centers, disinterest in nephrologists, and fear of self-cannulation by patients. From 1970 through 1993, 896 patients began dialysis at North Shore and were followed up through 1994. During this period, 687 patients were on in-center hemodialysis, 95 on CAPD, 74 on home hemodialysis, and 40 on in-center peritoneal dialysis. The home hemodialysis patients were younger, with a median age of 44 versus 59 years for in-center hemodialysis patients, and had less comorbidity. The home hemodialysis group had fewer diabetic patients and no renal vascular patients. The 5-year and median survival estimates were significantly better for the home hemodialysis patients versus other dialysis modalities. More home hemodialysis patients received transplants. Compared with the other dialysis modalities, home hemodialysis patients showed significantly improved survival rates. When matched by age, sex, and end-stage renal disease (ESRD) diagnosis to corresponding in-center hemodialysis, the home hemodialysis patients still had significantly better survival rates, but the home hemodialysis patients had less comorbidity. In conclusion, home hemodialysis patients survive longer and have better rehabilitation than other dialysis patients. Reasons for better survival in addition to a younger age and more favorable ESRD diagnosis may include less comorbidity, more patient involvement, and longer dialysis time. Because of these better outcomes, home hemodialysis should be offered to more ESRD patients.

Comparison of methods for measuring albumin in peritoneal dialysis and hemodialysis patients.

Serum albumin levels have been used extensively as an indicator of morbidity in patients with end-stage renal disease. Recent evidence suggests that albumin levels vary considerably in hemodialysis patients depending on the laboratory method used, but formulas for comparing albumin values by different methods have not been developed. We prospectively evaluated the effects of measuring albumin by three different methods on paired plasma and serum from 23 patients on continuous ambulatory peritoneal dialysis (CAPD) and 53 patients on chronic maintenance hemodialysis. Plasma and serum gave virtually identical results independent of method used. In CAPD patients, bromcresol green and nephelometry gave nearly identical albumin measurements through the entire range of plasma levels. In contrast, bromcresol purple gave values that were 9.9 percent +/- 1.3 percent lower (P < 0.05). Hemodialysis patients showed a similar pattern with close agreement between bromcresol green and nephelometry, but bromcresol purple gave lower albumin levels by 19.1 percent +/- 1.2 percent (P < 0.05). The discrepancy in albumin in CAPD patients was significantly less than in the hemodialysis patients (P < 0.05), suggesting that there were fewer interfering substances in the blood of CAPD patients than in hemodialysis patients. Linear regression analysis was used to develop simple formulas for comparing albumin values obtained by the different methods in CAPD and hemodialysis patients. These studies show that values for albumin in blood vary significantly by method of analysis in CAPD and hemodialysis patients. By the use of these formulas, it becomes possible to compare albumin values between centers using different methods for the purpose of quality management.

Minimal change nephropathy associated with sclerosing mesenteritis.

A 65-year-old man with sclerosing mesenteritis developed the nephrotic syndrome. Percutaneous renal biopsy revealed classical histologic findings of minimal change nephropathy with a mild interstitial nephritis. Immunomodulation with prednisone led to a rapid and complete remission of the proteinuria but did not alter the course of the underlying sclerosing mesenteritis. The association of lymphomatous and nonlymphomatous neoplasms with minimal change nephropathy has been well-described. Our review of the literature indicates a parallel association of malignant lymphoma with sclerosing mesenteritis and a variety of disorders that constitute a spectrum of disease. The occurrence of this histopathologic form of renal injury and therapeutic response in the setting of a known lymphoreticular disorder suggests a role for a generalized alteration in cell-mediated immunity and not a tumor-induced elaboration of a factor(s) that directly damages the glomerular filtration barrier.

Renal vascular disease causing end-stage renal disease, incidence, clinical correlates, and outcomes: a 20-year clinical experience.

In the United States, the incidence of end-stage renal disease to hypertension has increased sharply over the last 8 years, especially in elderly white dialysis patients who demonstrate very poor survival rates. The 5-year survival rates were near 20% for patients 65 to 74 years old and 9% for those > or = 75 years of age. Our program experienced a sharp increase in cases of end-stage renal disease due to renal vascular disease after 1982. Renal vascular disease was characterized clinically in 83 of 683 dialysis patients either by angiography or asymmetric kidney size in patients with evidence of systemic atherosclerosis, hypertension, insignificant proteinuria, and a benign urinary sediment. The median age was 70 years, with 84% of the patients being older than 61 years. These patients had 56% 2-year, 18% 5-year, and 5% 10-year survival rates, which are quite similar to the 1992 US Renal Data System data. Patients with renal vascular disease have a significantly worse prognosis than other diagnostic groups, most likely due to their older age, underlying vascular disease, and coronary artery disease. We feel that a significant number of elderly white hypertensive patients described in the 1992 US Renal Data Service report have renal vascular disease as a cause of end-stage renal disease, highlighting the need to establish correct renal diagnoses. Hypertension should not be the end-stage renal disease diagnosis in elderly white hypertensive patients if clinical criteria suggest a diagnosis of renal vascular disease.

Death by withdrawal from dialysis: a 20-year clinical experience.

The reasons for withdrawal from dialysis are not well understood. The goals of this study were to determine the risk of dying by withdrawal from dialysis over time and to elucidate pertinent clinical correlates in 716 long-term dialysis patients. These patients were monitored from the initiation of dialysis through the time of death, transplant or transfer to another program during a 20-yr period from 1970 through 1989. The causes of death in the 340 deceased patients were analyzed. Clinical correlates and associated risk factors were evaluated in the patients who died from withdrawal from dialysis. Withdrawal from dialysis was defined as: "Death with manifestations of uremia because of withdrawal from dialysis. Underlying medical conditions should not have been active, leading to rapid deterioration with imminent death." Withdrawal from dialysis and cardiac events were the second leading cause of death, each accounting for 18.5% of the deaths. Patients stopping dialysis were older at the start of dialysis than were patients dying of other causes (P < 0.0006; Kruskal-Wallis test), with 65.1% of these patients 61 yr of age and older. Cancer, malnutrition, catabolism, and "dissatisfaction with life" were important associations with the decision to withdraw. More than 50% of patients withdrawing from dialysis had either diabetic nephropathy or atherosclerotic renal vascular disease. Withdrawal from dialysis was a common cause of death in these dialysis patients especially if they were over 61 and had systemic diseases such as diabetes mellitus and renal vascular disease. The reasons for a higher incidence of withdrawal in certain programs deserve further study.

Mortality in dialysis patients: analysis of the causes of death.

The objective of this study was to identify the causes of death in maintenance dialysis patients who survived at least 90 days and were monitored during a 16-year period. Of 532 patients starting dialysis, 222 died. The causes of death were grouped into six categories: cardiac, infectious, withdrawal from dialysis, sudden, vascular, and "other." The greatest number of deaths were due to infections, followed by withdrawal from dialysis, cardiac, sudden death, vascular, and other. The risk of dying increased for the first 4 years of dialysis, decreased in years 5 through 10, and had a second increase at 11 years. The mortality during the first 4 years consisted largely of infectious and cardiac deaths. The late peak of deaths was mainly due to infections and withdrawal from dialysis. Overall, infections accounted for more than 36% of all deaths. Withdrawal occurred in 21.2% of the patients and was most common in patients over age 61. Notably, cardiac deaths accounted for only 14.4% of all deaths and no patient died from a cardiac cause after surviving on dialysis more than 8.5 years. We conclude that infection is the leading cause of death in our dialysis patient population. Withdrawal from dialysis was a common cause of death, especially in older patients. Cardiac mortality was not as frequent as anticipated and occurred mainly in patients on dialysis less than 4 years, suggesting that it is the result of preexisting disease.

Plasma angiotensins in anephric humans: evidence for an extrarenal angiotensin system.

The recent identification of messenger RNAs encoding renin and angiotensinogen in nonrenal tissues raises the possibility that angiotensins (Ang) may be formed extrarenally and released into the plasma. The aim of this investigation was to test the hypothesis that plasma angiotensins may originate from extrarenal sites. Twenty-five patients with chronic renal failure (six surgically anephric and 19 with kidneys in situ) were studied prior to and after a standard hemodialysis treatment. Angiotensins were measured by extraction, high-pressure liquid chromatography (HPLC) separation, and radioimmunoassays. In patients with kidneys present, plasma renin activity (PRA) was 3.1 +/- 0.7 ng Ang I/ml/h. Ang I, Ang II, and Ang III levels were 70.6 +/- 9.0, 44.0 +/- 9.8, and 20.2 +/- 3.6 pg/ml, respectively. In all six anephric patients PRA was undetectable (less than 0.1 ng Ang I/ml/h). Ang I and Ang II were detected in four anephric patients, and Ang III was detected in three anephric patients (Ang I, 10.4 +/- 5.2; Ang II, 2.6 +/- 1.2; Ang III, 2.7 +/- 1.5 pg/ml, n = 6). At the completion of dialysis treatments, which reduced body weight by 2.5 +/- 0.2 kg in patients with kidneys and by 2.1 +/- 0.3 kg in anephric patients, there were no significant changes in PRA or plasma angiotensins in either group. Reduction in body water by hemodialysis did not increase the concentration of angiotensins in plasma. We conclude that there is a small but definite component of plasma angiotensin that is produced by nonrenal mechanisms and that is not stimulated by volume depletion.

Osteoarthropathy of patients undergoing long-term hemodialysis.

Maintenance hemodialysis, while capable of prolonging life, is an incomplete substitute for the patient's native functioning kidneys. Recently, it has become clear with time that long-term survivors of hemodialysis develop an osteoarthropathy differing from classic secondary hyperparathyroidism. The radiographic appearance includes erosive or destructive changes of articular surfaces, bone cysts, osteopenia, and periarticular calcific deposits. The most important clinical factor related to the development of the disease is increasing duration of hemodialysis. Although amyloid appears to be a causative factor, the exact etiology and treatment remain uncertain. It is important that the radiologist be aware of this entity and not mistake it for secondary hyperparathroidism, a variant of rheumatoid arthritis or infection.

Serum erythropoietin levels and hematocrit in end-stage renal disease: influence of the mode of dialysis.

Serum erythropoietin (Ep) levels were measured by radioimmunoassay in 70 patients with end-stage renal disease (ESRD) to evaluate the influence of the mode of dialysis on the relationship between serum Ep levels and the severity of anemia. Thirty-five patients were on hemodialysis (HD), seven were on intermittent peritoneal dialysis (IPD), and 28 were on continuous ambulatory peritoneal dialysis (CAPD). Compared to HD, CAPD patients had higher serum Ep (CAPD), 46.1 +/- 13.4 v HD, 16.9 +/- 2.2 mU/mL) and hematocrit (CAPD, 33.9 +/- 2.5 v HD, 24.8 +/- 1.4%; P less than 0.05). The Ep and Hct values for IPD patients were intermediate between the other two groups. Serum Ep levels were higher in CAPD patients in the first 4 weeks of initiation of CAPD (144 +/- 35 mU/mL, n = 6) than later (39 +/- 6.4 mU/mL, n = 24). A significant fluctuation in serum Ep and Hct values was noted in patients on all three modes of dialysis, when multiple samples were obtained at different time intervals. There was a weak correlation between serum Ep and Hct in the three groups of dialysis patients; r = 0.36, P less than 0.005. The data suggest that CAPD provides a better biochemical milieu for Ep production and responsiveness than HD treatment of ESRD.

Reduction in liver iron in hemodialysis patients with transfusional iron overload by deferoxamine mesylate.

Four hemodialysis patients with transfusional iron overload were treated with three times weekly intravenous (IV) deferoxamine mesylate during the dialysis treatment. Using a gamma ray scattering technique, significant reductions in liver iron content were documented, with a mean follow-up of 20 months. Three of the four patients showed significant improvements in liver enzymes. This decrease in liver iron content could not be predicted by clinical parameters or serum ferritin. Therapy proved to be safe and effective, but follow-up requires monitoring of tissue iron by means other than standard laboratory tests.

Spondyloarthropathy from long-term hemodialysis.

Twenty-six patients undergoing long-term hemodialysis who had hand and wrist abnormalities were examined for the presence of concurrent spinal disease. Six patients (23%) were found to have spinal disease on radiographs. In four, the findings resembled those of a destructive spondyloarthropathy, and in two, a less destructive erosive arthritis. A review of the spinal radiographs of 31 patients with normal hands and wrists revealed no such abnormalities. Postmortem examinations of two patients with spondyloarthropathy demonstrated extensive deposition of beta-2 microglobulin, an amyloid-like substance. The authors conclude that the disease is similar in both areas and represents a skeletal response to chronic renal failure and long-term hemodialysis. The disease may occur more frequently with an increased duration of hemodialysis, in one area of the skeleton if another area is already affected, and is probably not infectious if multiple areas are involved.

Predictors of survival in patients undergoing dialysis.

Survival and risk analyses were performed on all 532 patients in whom long-term dialysis was started from 1970 through 1985. During this 16-year period, starting age increased from 47 to 60 years (p less than 0.001), and the incidence of diabetes mellitus and renal vascular disease increased. Survival analysis showed age, renal diagnosis, type of dialysis, and year starting dialysis to be important predictors of survival. There was a fourfold rise in the risk ratio as starting age increased from 25 to 65 years. The risk was 1.5 times higher for those patients who did not start dialysis in 1978 through 1981 than for those who did. Risk decreased fivefold for patients choosing home hemodialysis. Home hemodialysis patients survived longer compared with patients utilizing other dialysis modalities, possibly because of a younger average age and a lower incidence of diabetes mellitus and renal vascular disease. There was greater than a threefold rise in risk ratio with the diagnosis of diabetes mellitus compared with either chronic glomerulonephritis or polycystic kidney disease. Older patients and those with diabetes mellitus formed the high-risk group; these two characteristics have been increasing during the last eight years of the study. It is concluded that although patients with high risk have an increased and a high mortality, overall survival has improved.

Osteoarthropathy of the hand and wrist in patients undergoing long-term hemodialysis.

Radiographs of the hand and wrist in 81 patients who had undergone hemodialysis for a minimum of 5 years (mean, 7.8 years) were reviewed. In 32 patients arthritic changes were found, consisting of articular erosions, joint space narrowings, periarticular cysts, and osteopenia. Seven of the 32 patients had periarticular calcific deposits. The frequency and severity of the radiographic findings increased with increasing duration of dialysis. It appears that in addition to the well-recognized secondary hyperparathyroidism there is another commonly occurring osteoarthropathy (40% in this series) related to long-term hemodialysis.

Role of erythropoietin in the reversal of anemia of renal failure with continuous ambulatory peritoneal dialysis.

We report serum erythropoietin levels in a patient who showed significant improvement in hematocrit when switched from hemodialysis to continuous ambulatory peritoneal dialysis (CAPD) treatment. This 22-year-old woman had severe anemia and low serum immunoreactive erythropoietin levels (8.0 +/- 1.2 mU/ml; n = 5) while on hemodialysis for 7 years. Serum erythropoietin levels were 80 and 177 mU/ml, 2 and 3 weeks, respectively, after starting CAPD. This was followed by an increase in reticulocyte count from 3.9 to 22% and hematocrit from 19 to 48%. The serum erythropoietin concentration obtained on CAPD treatment (62.7 +/- 15.2 mU/ml; n = 9) was significantly higher than that obtained on hemodialysis. Our findings indicate that CAPD facilitates increased erythropoietin production compared to hemodialysis and that the anemia of uremia may reverse if sufficient erythropoietin is available.

Nondilated obstructive uropathy: percutaneous nephrostomy performed to reverse renal failure.

Ureteral obstruction can lead to renal failure without involving detectable dilatation of the calyces, renal pelvis, or ureter proximal to the obstruction. This phenomenon was noted in seven patients who had clinical obstruction that we were not able to diagnose using computed tomography (CT) or ultrasonography (US). These patients underwent percutaneous nephrostomy (PCN), which resulted in brisk diuresis and improved renal function. We obtained an accompanying antegrade urogram in these cases, which demonstrated the level of obstruction and indicated that dilatation of the collecting system was minimal or not present. When obstructive uropathy is suspected, we believe it is essential to consider performing PCN to evaluate and potentially reverse renal failure, even when CT and US scanning do not demonstrate obstruction.

Listeriosis in patients with long-term hemodialysis and transfusional iron overload.

Over a four-year interval, four cases of Listeria monocytogenes bacteremia were observed among a population of 127 patients undergoing long-term hemodialysis. None had an underlying malignancy or were recently receiving immunosuppressive medications. A search for a predisposing factor suggested a relationship to transfusional iron overload. Although still a rare infection, the possibility of listeriosis must be kept in mind by physicians caring for patients undergoing hemodialysis, particularly those requiring blood transfusions.

Nuclear resonance scattering measurement of human iron stores.

Hepatic iron stores were measured noninvasively in 31 patients (thalassemia, hemodialysis, hemosiderosis, refractory anemia) with suspected iron overload, employing a nuclear resonance scattering (NRS) technique. The thalassemia patients were undergoing desferrioxamine chelation therapy during the NRS measurements. The hemodialysis patients were measured before chelation therapy. Iron levels measured by NRS were in general agreement with those determined in liver biopsies by atomic absorption spectroscopy. In addition, NRS measurements from the thorax of some of these patients suggest that this method may also prove useful for clinical assessment of cardiac iron.