Uremia Therapy Research Articles

Excess Morbidity in Patients with Uremia Therapy without Prior Care by a Nephrologist. Ifudu O, Dawood M, Homel P, Friedman EA. Am J Kidney Dis 28:841–845, 1996

Excess Morbidity in Patients with Uremia Therapy without Prior Care by a Nephrologist. Ifudu O, Dawood M, Homel P, Friedman EA. <i>Am J Kidney Dis</i> 28:841–845, 1996

Uremia therapy in patients with end-stage renal disease and human immunodeficiency virus infection: has the outcome changed in the 1990s?

We conducted a cross-sectional survey to determine the relative course of patients with end-stage renal disease (ESRD) and human immunodeficiency virus (HIV) infection sustained on maintenance hemodialysis. All 34 patients with ESRD and HIV infection receiving hemodialysis in one hospital-based and three community-based outpatient hemodialysis facilities in Brooklyn, NY, were studied. We documented their known duration of HIV infection, duration of ESRD, and hemodialysis prescription, and noted the presence of clinical acquired immunodeficiency syndrome (AIDS). Total CD 4 count, serum albumin concentration, and percent reduction of urea (predialysis blood urea nitrogen minus postdialysis blood urea nitrogen, divided by predialysis blood urea nitrogen × 100) were measured. The 34 study subjects (26 men and eight women) included 31 blacks (91%) and three Hispanics (9%) with a mean age of 42 ± 7.5 years, 29 (85%) of whom had AIDS. Twenty subjects (59%) had a history of intravenous drug abuse. Only six subjects (18%) were receiving an antiretroviral drug (zidovudine = five, dideoxyinosine = one). In 23 subjects (68%), AIDS was diagnosed prior to ESRD and was presumed to be the cause of renal failure (HIV-associated nephropathy). The mean known duration of HIV infection was 50.5 ± 34 months (median, 48 months); the mean duration of ESRD was 57 ± 50 months, the mean total CD 4 count was 140 ± 150 cells/μL (median, 70 cells/μL), the mean hematocrit was 28% ± 5%, and the mean serum albumin concentration was 3.5 ± 0.37 g/dL. All subjects were receiving erythropoietin for anemia correction. The mean length of the prescribed thrice-weekly hemodialysis sessions was 3.5 ± 0.4 hours. Our results suggest that the survival of many ESRD patients with HIV infection receiving hemodialysis has improved compared with the uniformly dismal survival rate reported in the 1980s. Decisions on whether to initiate renal replacement therapy in patients with AIDS and advanced renal failure should be individualized because the combination of ESRD and HIV infection does not necessarily signal near-term death.

Relative contributions of body iron status and uremia severity to anemia in patients with advanced chronic renal failure.

Anemia in chronic renal failure is predominantly caused by diminished erythropoietin synthesis by diseased kidneys. While iron deficiency is often stated as a cause of anemia in chronic renal failure prior to end-stage renal disease, its relative contribution is debated. It is speculated that rather than frank 'iron deficiency', many patients with chronic renal failure may indeed have impaired utilization of iron. We analyzed 139 consecutive patients with chronic renal failure starting maintenance hemodialysis to determine the relationship between hematocrit, measures of renal function (blood urea nitrogen and serum creatinine concentration), and measures of iron availability (serum transferrin saturation, serum iron level and serum ferritin). The 139 study subjects (60 men, 79 women) comprised 116 blacks (83%), 15 hispanics (11%), and 8 whites (6%) of a mean age 56 +/- 15 years. Only 23 (17%) of 139 subjects had positive hemoccult stool test for blood. Their mean hematocrit was 24 +/- 4.5%, mean blood urea nitrogen concentration was 121 +/- 38, mean serum creatinine concentration was 12.6 +/- 5.2 mg/dl, mean serum transferrin saturation was 22 +/- 14%, mean serum ferritin level was 235 +/- 194 U/l, mean serum iron level was 55 +/- 40 U/l, and mean total iron binding capacity was 254 +/- 93%. Multiple regression analysis with hematocrit as the outcome variable, and blood urea nitrogen level, serum creatinine concentration, serum albumin concentration, serum transferrin saturation, and serum ferritin level as the independent variables, showed an inverse correlation between hematocrit and serum creatinine concentration (p = 0.002). We conclude that in patients with chronic renal failure starting uremia therapy, anemia does not correlate with any of the commonly measured indices of body iron stores. We infer that impaired utilization of iron may be a significant factor in the anemia of chronic renal failure.

Excess morbidity in patients starting uremia therapy without prior care by a nephrologist

Many inner-city residents with progressive renal disease do not receive specialist care from a nephrologist, and often arrive in the emergency room manifesting life-threatening uremic symptoms requiring emergency rescue dialysis. We examined the relationship between the quality of medical care received during progression to end-stage renal disease, and the clinical condition and morbidity at initiation of renal replacement therapy. During a 5-year period (January 1990 to December 1994), we prospectively studied 139 consecutive inner-city residents with a confirmed diagnosis of chronic renal failure who were starting uremia therapy. At onset of study, subjects were sorted into one of three groups depending on the extent of medical care received during the 3 years immediately preceding initiation of hemodialysis: nephrologist, nonnephrologist (physician), or no medical care. Information obtained from each subject included length of hospital stay during the admission for initiation of dialysis therapy and the type of hemodialysis vascular access used for first dialysis treatment (permanent v temporary). Predialysis blood urea nitrogen concentration, serum creatinine concentration, serum albumin concentration, and serum bicarbonate concentration were measured once immediately before the first dialysis. The 139 study subjects (62 men and 77 women) comprised 116 blacks (83%), 15 Hispanics (11%), and eight whites (6%), and had a mean age of 56 ± 15 years (±SD). Only 59 (43%) subjects received prior specialist nephrologist care, and their mean length of hospital stay (12 ± 23 days) was shorter than that of subjects who received nonnephrologist care (n = 63 [45%]; 25 ± 21 days) or those who received no prior medical care (n = 17 [12%]; 29 ± 23 days) ( P = 0.002). Temporary hemodialysis vascular access was used for the first dialysis in all 17 (100%) of the subjects with no prior medical care, in 56 (89%) of the 63 subjects who received prior care from a nonnephrologist, and in 21 (36%) of the 59 subjects who received prior care from a nephrologist ( P = 0.0001). Subjects who received prior care from a nephrologist had a lower mean serum creatinine concentration at initiation of dialysis (11 ± 4.4 mg/dL) than did either the subjects who received nonnephrologist care (13 ± 5.4 mg/dL) or no medical care (16 ± 5.7 mg/dL) ( P = 0.003). In addition, subjects who received prior care from a nephrologist had less severe metabolic acidosis than the subjects in the other two groups ( P = 0.04). We infer that initiation of uremia therapy is delayed in inner-city residents with progressive renal failure who do not receive specialist nephrologic care, and that as a consequence these patients suffer excess short-term morbidity.

Enrollment parathyroid hormone level is a new marker of survival in hemodialysis and peritoneal dialysis therapy for uremia

The relatively high morbidity and mortality during dialytic therapy for end-stage renal disease (ESRD) in the United States is the subject of current inquiry. Identified risk factors for excess mortality include advanced age, diabetes, and malnutrition exemplified by a low serum albumin level. Parathyroid hormone (PTH) has long been thought to contribute to the toxicity of the uremic syndrome. We reviewed the course of patients maintained by hemodialysis (HD) and peritoneal dialysis (PD) to detect any correlation between the level of PTH when beginning dialytic therapy and subsequent morbidity and mortality. Study cohorts consisted of 175 HD and 113 PD patients followed for up to 9 years. Demographic characteristics such as age, race, gender, diabetic status, and prior months on dialysis, as well as biochemical parameters including albumin, creatinine, cholesterol, intact PTH, calcium, and phosphorus levels at enrollment were evaluated for their effect on patient survival. Expected survival was calculated by Cox proportional hazards analysis. Older age and lower enrollment serum creatinine level were associated with increased mortality in both HD and PD patients, whereas low serum albumin and low serum cholesterol levels also predicted high mortality in HD patients. In both HD and PD, patients with enrollment PTH level of ≤ 65 pg/mL had more than twice the mortality risk of those with PTH ≥ 200 pg/mL. Both observed and expected survival of patients with low PTH were significantly lower than the survival in patients with higher PTH. Five-year HD survivors and four-year PD survivors had significantly higher PTH levels at initiation of dialytic therapy than did those with shorter survival. PTH level correlated with serum creatinine and serum albumin in HD but only with serum creatinine in PD, supporting the inference that patients with high enrollment PTH were better nourished than those with lower PTH.

Bowel as a kidney substitute in renal failure

Maintenance peritoneal dialysis and hemodialysis sustain the lives of approximately 250,000 uremic patients in industrialized nations worldwide. The cost of uremia therapy, however, exceeds health care budgets in developing countries. As a consequence, most of those alive today have no chance of effective treatment should their kidneys fail. Extraction, modification, or recycling of nitrogenous wastes by the gastrointestinal tract is a potentially low-cost means of substituting for missing renal function. Multiple approaches to the bowel as a substitute kidney have been attempted. Direct removal of nitrogen-containing compounds by an external gut fistula, gastric, ileal, or colonic gavage (dialysis) or induced diarrhea extract water and urea but only minimal amounts of larger molecules such as creatinine. Binding of nitrogen compounds to inert orally administered sorbents such as charcoal or oxystarch has been pursued in advanced uremia. Modification of nitrogen compounds by ingesting enzymes derived from soil bacteria or packaged in artificial cells is an approach that, although exciting, is incompletely evaluated. Evidence indicates that strains of bacteria can be induced to synthesize enzymes that recycle urea and other nitrogen compounds retained by uremic individuals. Clinical trials to substantiate uncontrolled trials of bowel substitution in renal failure will, if positive, accelerate development of a practical regimen to extend life where no other means are possible.

Prealbumin is the best nutritional predictor of survival in hemodialysis and peritoneal dialysis

Patients undergoing dialytic therapy for end-stage renal disease (ESRD) have greater morbidity and mortality than age-matched individuals with similar demographics in the general population. Risk factors for early death during treatment for ESRD include advanced age, diabetes, hypertension, and malnutrition. We questioned whether the level of serum prealbumin at the start of uremia therapy might serve as a marker of subsequent survival in patients treated with maintenance hemodialysis (HD) and peritoneal dialysis (PD). Study cohorts included 111 HD and 78 PD patients followed for up to 5 years. Selected demographic characteristics and biochemical variables were tested for correlation with survival in each cohort. Variables evaluated included age, race, gender, diabetic status, and serum concentrations of albumin, creatinine, cholesterol, and prealbumin. For comparison, expected survival was calculated with Cox proportional hazards analysis, which accounts for confounding variables. We found that a higher relative risk (RR) of death in HD patients correlated with older age, the diagnosis of diabetes, and a serum prealbumin < 30 mg/dL. In PD patients, older age and the presence of diabetes correlated with a higher RR of death than in the standard population. When nutritional variables were analyzed separately, prealbumin < 30 mg/dL was the strongest variable that predicted mortality in HD patients (RR = 2.64, P = 0.002) and also predicted increased risk of mortality in PD patients (RR = 1.8, P = 0.035). Observed and expected survival was significantly higher in patients with enrollment prealbumin greater than 30 mg/dL in both HD and PD. The serum prealbumin level correlated significantly with other measures of nutrition, including serum albumin, serum creatinine, and serum cholesterol, in both HD and PD patients. Among tested markers of nutritional status, prealbumin level appears to be the single best nutritional predictor of survival in ESRD patients.

Hyperlipidemia in children: the role of uremia, steroids and cyclosporine therapy.

At present, there are very few studies that look at the effect of uremia, prednisone and cyclosporine therapy on the lipid profiles of children. This effect is important because of the potential association of hyperlipidemia and increased risk of cardiovascular morbidity and mortality and glomerulosclerosis. We measured fasting lipid profiles in 73 children. There were 21 controls, 18 patients treated with cyclosporine and prednisone, 9 patients treated with cyclosporine alone and 25 dialysis patients. Lipoprotein (a) levels were measured using direct binding 'sandwich' ELISA. Uremic children had higher levels of triglycerides and very-low-density lipoprotein as compared with the control group. Children receiving combination of cyclosporine and prednisone also had higher total cholesterol, triglycerides, low-density lipoprotein, very-low-density lipoprotein as compared to the control group. However, children receiving cyclosporine monotherapy had lipid profiles similar to the control group. Patients receiving cyclosporine and prednisone had higher total cholesterol, high-density lipoprotein and low-density lipoprotein as compared with the dialysis group. Evaluating lipoprotein (a) levels, children on cyclosporine monotherapy had lower lipoprotein (a) levels as compared with children on dialysis and those receiving both combination therapy. The total cholesterol/high-density lipoprotein-cholesterol ratio (TC/HDL) was similar among the study groups. In summary, uremic children and children receiving steroids with cyclosporine have elevated lipid levels. However, the increased risk for atherosclerosis is not evident because of similar levels of lipoprotein (a) and TC/HDL ratios among the study groups.

Resurgence of blood transfusion therapy in erythropoietin treated hemodialysis patients.

Anemia, a major component of the uremia syndrome before the introduction of recombinant human erythropoietin (EPO), was treated primarily with blood transfusions in patients with end-stage renal disease (ESRD). After multi-center trials of EPO in hemodialysis patients showed that blood transfusion requirements fell by > or = 50% in hemodialysis facilities using EPO, it was anticipated that blood transfusion therapy in hemodialysis patients would be eliminated in patients treated with EPO. The authors examined the annual rate of blood transfusions from 1983 to 1992 in hemodialysis patients admitted to an inner city municipal hospital. Hospital computer records were accessed to obtain a list of all patients admitted to the hospital who received a blood transfusion between 1983 and 1992. From these data, lists of transfused hemodialysis patients were generated. The authors compared the mean annual blood transfusion rate per hospital patient in the pre EPO era (1983-1985) with the same rate during the time of EPO trial (1986-1988) and during the time of wide clinical availability of EPO (1989-1992). In addition, the authors examined individual hospital medical records of hemodialysis patients who received transfusions in 1986 and 1992. The mean annual blood transfusion rate was 38% (range, 36-39%) in the pre EPO era, 19% (range, 16-24%) during the years of the EPO trial, and 23% (range, 21-24%) after EPO was widely used in 1989, comparing the latest rate with either of the two earlier times (p < 0.0001). Of all of the years tabulated, the blood transfusion rate was lowest in 1987, the second year of the EPO clinical trial, with only 94 (16%) of 592 hemodialyzed patients given a blood transfusion. The rate of blood transfusions remained low in 1988 (18%) but subsequently has increased. Using 1987 as a reference point, the rate of blood transfusion in hemodialysis patients increased in each of the subsequent years after 1988 (18%, p < 0.33); 1989 (23%, p < 0.001), 1990 (24%, p < 0.0001), 1991 (21%, p < 0.02), and 1992 (23%, p < 0.0001). The authors conclude that, despite the availability and broad use of EPO in uremia therapy since 1989, a significant proportion of hemodialysis patients receiving EPO treatment require blood transfusions for anemia.

Facing the Reality: The World Cannot Afford Uremia Therapy at the Start of the 21st Century

Although remarkably successful in prolonging useful life, there is minimal probability that the majority of the world's population will benefit from contemporary therapy for irreversible renal failure because of its inordinately high cost in light of available resources. While affluent nations establish priorities for allocation of slots for maintenance dialysis of recipients of organ transplants, poor and developing countries must await the development of inexpensive, low technology treatments to substitute for absent kidney function. One attractive potential alternative to contemporary uremia therapy is the use of the intestine as a giant substitute and somewhat displaced nephron. Possible means of extracting wastes via the gut include ingestion of a mixed oral sorbent, instillation of bacterial crystallized enzymes to transform nitrogenous wastes to essential amino acids, or administration of high osmolality laxatives to promote diarrhea containing nitrogenous wastes. Any of these approaches may extract sufficient solute and water to sustain anephric life. An optimistic view of evolving uremia therapy is that within the next decade pills and purges for the poor may supplant more effective though expensive high technology approaches now encompassed in so-called modern nephrology.

H reflexes as a measure for uremic polyneuropathy. A longitudinal study in patients treated with dialysis or renal transplantation

Assessment of peripheral nerve function in end stage uremia by clinical and conventional nerve conduction velocity studies was compared to that using H reflex measurements. The latter proved to be most sensitive technique. The results of the test correlated well with clinical and with other neuro-physiological measures. Nerve function as evaluated by H reflexes remained stable during the first 2 years of dialysis, but deteriorated later on. H reflex latencies shortened after renal transplantation. The results of H reflex measurements did not correlate with biochemical parameters, which makes the test a less attractive overall measure for the efficiency of therapy in uremia. In the follow-up of patients under treatment for uremic polyneuropathy, however, recording of H reflexes provides an important measure.

H reflexes as a measure for uremic polyneuropathy. A longitudinal study in patients treated with dialysis or renal transplantation

Assessment of peripheral nerve function in end stage uremia by clinical and conventional nerve conduction velocity studies was compared to that using H reflex measurements. The latter proved to be most sensitive technique. The results of the test correlated well with clinical and with other neuro-physiological measures. Nerve function as evaluated by H reflexes remained stable during the first 2 years of dialysis, but deteriorated later on. H reflex latencies shortened after renal transplantation. The results of H reflex measurements did not correlate with biochemical parameters, which makes the test a less attractive overall measure for the efficiency of therapy in uremia. In the follow-up of patients under treatment for uremic polyneuropathy, however, recording of H reflexes provides an important measure.

The ARRT of Uremia Therapy

The ARRT of Uremia Therapy

Clinical aspects of cardiomyopathy in dialysis patients.

The burden of cardiac disease in dialysis patients is high. Congestive heart failure, ischemic heart disease, left ventricular hypertrophy, and systolic dysfunction occur frequently and are associated with an adverse prognosis. In addition, during dialysis therapy anemia, hypoalbuminemia, low blood pressure, and lower serum creatinine levels are adverse predictors of mortality. Risk factors for systolic dysfunction include older age, ischemic heart disease, hyperparathyroidism, and smoking. Risk factors for left ventricular hypertrophy include older age, hypertension, anemia, and diabetes mellitus. Interventions with potential for improving cardiomyopathy include normalization of hematocrit with erythropoietin, improved uremia therapy, and angiotensin-converting enzyme inhibitors. Trials to determine the most appropriate interventions to reduce the impact of cardiac disease in chronic uremia are urgently required.

Dialytic therapy for diabetic patients with terminal renal failure.

Diabetes mellitus is the leading cause of irreversible renal failure in the United States, Japan, and industrialized Europe. Of those diabetic patients begun on uremia therapy, 80% are treated with hemodialysis and 12% with peritoneal dialysis. Continuous ambulatory peritoneal dialysis is proposed by some as appropriate primary therapy for many diabetics with end-stage renal disease (ESRD), but peritonitis is common at one episode per 11 to 21 patient-months. Cardiovascular disease is accelerated in patients with diabetic ESRD and is the most common cause of death in diabetic dialysis patients. Although survival of diabetic ESRD patients is lower than that of nondiabetic patients (1- and 5-year patient survival is 74% and 19%, respectively, in diabetics and 78% and 40%, respectively, in all ESRD patients), morbidity and mortality figures have improved steadily over the past two decades. When possible, renal transplantation is advised as the treatment most likely to effect rehabilitation and long survival.

Diabetic nephropathy. Management of the end-stage patient.

Diabetic nephropathy is currently the leading cause of new patients requiring dialysis in the United States. Management of the diabetic patient with ESRD is complicated by the frequent coexistence of complications affecting other organ systems, including retinopathy, cardiovascular disease, peripheral neuropathy, or autonomic neuropathy, manifested as gastroparesis, diarrhea or obstipation, cystopathy, or orthostatic hypotension. Associated clinical syndromes must be followed and treated, if possible, while preparing the patient to receive renal replacement therapy. Both the clinical condition and the psychosocial environment are key factors in choice of ESRD therapy for an individual patient. Rehabilitation data are best for patients who undergo kidney transplantation, but these data are confounded by the fact that the healthiest patients are referred for this treatment modality. Living, related kidney transplant is the preferred initial choice for the diabetic patient with kidney disease. At most centers, both in the United States and abroad, the cadaveric transplant is the second choice for uremia therapy. At the appropriate institution, the patient with type I diabetes may also be considered for a simultaneous cadaveric pancreas transplant. While awaiting cadaveric transplantation, or if contraindication to transplantation is present (chronic infection, recent malignancy, or severe cardiac disease), diabetic patients with severe impairment of the glomerular filtration rate (less than 10-15 ml/min) are referred for vascular access placement and/or insertion of a peritoneal catheter. The decision regarding the choice of CAPD vs. hemodialysis must be made on an individual basis. Rehabilitation and survival data for these therapies are similar, although technique survival rates for CAPD decline dramatically as time progresses because of infectious complications. In-center hemodialysis has the worst survival and rehabilitation profile, but the sickest, most debilitated patients with the highest number of comorbid conditions tend to be referred for that therapeutic modality. Most studies of rehabilitation were performed before use of recombinant human erythropoietin, and comparison between ESRD treatment modalities will have to be reevaluated now that the drug is routinely used.

Rationing of uremia therapy.

Rationing of uremia therapy.

Hypercalciuria Due to Combined Growth Hormone and Calcitriol Therapy in Uremia: Effects of Growth Hormone on Mineral Homeostasis in 75% Nephrectomized Weanling Rats

The administration of growth hormone (GH) in conjunction with calcitriol in uremia may increase urinary calcium and decrease renal phosphate excretion, which could have an adverse effect on the kidney in chronic renal insufficiency. The effect of 40 d of ovine GH, calcitriol, and the combination of GH and calcitriol on mineral excretion was studied in rapidly growing uremic rats. Uremia was produced by 75% nephrectomy, and the animals were fed a diet containing 8% protein with equal quantities of calcium (0.6%) and phosphate (0.6%). The uremic rats treated with ovine GH were significantly longer and heavier than the uremic control rats and the uremic rats treated with calcitriol alone. However, the combination of calcitriol and GH abolished the beneficial effect of GH on growth and increased urinary calcium excretion 4-fold over uremic controls whether expressed as calcium excretion per 100 g body weight, urine calcium to creatinine ratio, or as fractional calcium excretion. Calcitriol therapy alone also significantly increased calcium excretion, but not to the extent that the combination therapy did. This increased urinary calcium excretion in the GH plus calcitriol group was not associated with an increase in calcium and sodium intake, plasma ionized calcium, or urinary sodium excretion. The calcium content of the femurs from all uremic rat groups was significantly lower than that of the sham control rats; however, there was also no further decrease in bone calcium content in the GH plus calcitriol group compared with uremic controls. This indicated that bone was not the source of this excess urinary calcium.(ABSTRACT TRUNCATED AT 250 WORDS)

Hemodialysis and the Elderly Patient: Potential Advantages as to Quality of Life, Urea Generation, Serum Creatinine, and Less Interdialytic Weight Gain

A total of 204 patients treated by maintenance hemodialysis or continuous ambulatory peritoneal dialysis (CAPD) were studied to ascertain how advancing age influences adaptation to uremia therapy. No difference in Karnofsky score was noted among patients over 70 years of age and two groups of patients, 16 to 59, and 60 to 69 years of age, respectively. In a subset of 33 hemodialysis patients studied midweek, it was noted that increasing age is associated with a lower serum creatinine concentration, lower interdialytic weight gain, and a lower urea generation rate. These three findings contribute to a relative ease in treating older uremia patients with hemodialysis or CAPD, as they tend to be stable and compliant relative to younger patients.

Transcellular Disequilibrium and Intradialytic Catabolism Reduce the Reliability of Urea Kinetic Formulas

To elucidate the limits of single-pool models as regard aberrations induced by urea transcompartmental disequilibrium during urea kinetics, mass balances and fractional clearances were studied, and original formulas developed to calculate urea clearance and distribution volume. In the early dialytic phases, aberrations were more evident, with low kinetic volume (VK) values and kinetic clearance (KK) values double those obtained by dialysate collection (KDC). Over the whole session, both VDC and VK were underestimated (9.9 and 8.2%), compared with anthropometric data (VA). In 3 patients, the comparison of VA and VDC, and the behavior of effective body water clearance (KE), agreed with the hypothesis of dialysis-induced catabolism. Both disequilibrium and hypercatabolism can affect the reliability of the single-pool urea kinetic model; because of overlap, their effects are difficult to separate, and became particularly important in high-efficiency dialysis. A modified model, using V and CtET as input is suggested in order to establish the most appropriate dialysis prescription for uremia therapy.