Acute rhabdomyolysis associated with an echovirus 9 infection.

A 28-year-old long-distance runner experienced fever, chills, and brown urine 24 hours after a six-mile run. This was accompanied by a large rise in the creatine phosphokinase level and a rise in echovirus 9 titers from 1:16 to greater than 1:256 during a two-week period. A muscle biopsy specimen showed acute rhabdomyolysis, but no viral inclusion particles. Muscle energy metabolism analysis demonstrated no abnormalities. The patient was treated with forced saline diuresis, and he maintained normal renal function. He subsequently returned to long-distance running and has remained well for one year after the episode. This represents the first reported case, to our knowledge, of acute rhabdomyolysis associated with an echovirus 9 infection.

Bretylium kinetics in renal insufficiency.

Bretylium kinetics were examined in patients with varying degrees of renal impairment after a single intravenous dose of bretylium tosylate. Maximum plasma concentrations achieved at the end of the infusion, when normalized to the dose, correlated strongly with creatinine clearance. Drug disposition from plasma was biexponential, with a short distributive phase, but drug elimination was reduced, especially in patients with creatinine clearance below 30 ml/min X 1.73 m2. There was reduction in renal and total clearance and prolongation of t 1/2, with deteriorating renal function. In one patient who was reevaluated after a year, there was 76% reduction in the total clearance, corresponding to 43% deterioration of renal function. The difference of 33% between these values is due to a reduction of nearly 36% in volume of distribution, caused by the further deterioration of the renal function. Six-hour hemodialysis procedure on two anephric patients, resulted in an apparent one- to threefold increase in the computed bretylium clearance during dialysis, but the fraction of the total body load eliminated during the same period was not proportionally significant. The strong linear relationships between renal and total clearance, beta, and the creatinine clearance, may be helpful in adjusting dosage regimens for bretylium in patients with renal dysfunction.

Nephrotic-range proteinuria and hyperglycemia associated with clonidine therapy.

Glycosuria, hyperglycemia, and nephrotic-range proteinuria developed in a 68-year-old patient after clonidine was added to a stable antihypertensive regimen, which included metoprolol, of three years' duration. He later became glucose-intolerant with fasting hyperglycemia. Clonidine has been reported to transiently impair glucose tolerance. Persistent diabetes in a previously normoglycemic patient following clonidine has not been reported, and it supports the possibility that clonidine and metoprolol may have additive effects in suppressing endogenous insulin secretion.

The prognostic value of the eosinophil in acute renal allograft rejection.

A case report of marked peripheral blood eosinophilia and eosinophilic infiltration of a rejected renal allograft in a transplant recipient stimulated our review of the clinical course of 132 consecutive renal transplant recipients. A total of 187 acute rejections occurred in 112 patients. Diagnosis was made by renal biopsy in 124 cases. The percentage of eosinophils in the leukocyte differential of patients with irreversible rejection was 5.2 +/- 5.7 (mean +/- SD) versus that seen in patients with reversible rejection, 2.9 +/- 3.5 (P less than .05). The difference in the total eosinophil counts in each group was not statistically significant. Patients with peripheral blood eosinophil percentages greater than or equal to 4% had a 37.9% irreversible rejection rate, whereas those who had less than 4%, had a 22.4% loss rate (P less than .01). Six of seven patients with greater than or equal to 2% eosinophils in the inflammatory infiltrate of their renal allograft lost their kidney, whereas grafts with less than 2% eosinophils had a 36.8% loss rate (P less than .02). We conclude that the increased presence of eosinophils in the peripheral blood and/or renal allograft biopsy specimen is an adverse prognostic factor for acute rejection outcome.

Reevaluation of T cell subset monitoring in cyclosporine-treated renal allograft recipients.

The predictive value of peripheral blood T cell subset monitoring in renal allograft recipients has been questionable, and there has been no information concerning the correlation of T cell subset changes with the clinical event related to cyclosporine nephrotoxicity. This study was conducted to investigate the clinical usefulness of serial T cell subset monitoring in 34 consecutive renal transplant patients treated with cyclosporine by determining the total peripheral lymphocyte count and T cell subset counts using Leu-4, Leu-3ab, and Leu-2a monoclonal antibodies and flow cytometry up to 6 months after transplantation. The absolute counts of all cells were lower in transplanted patients than those of normal controls, but were not different from those of hemodialysis patients. During infection, the helper/suppressor (H/S) ratio and the cell counts, except for suppressor cells, decreased significantly. Within one week prior to rejection, all cell counts also decreased significantly. Furthermore, cell counts before steroid-resistant rejection were significantly lower than those before steroid-responsive rejection. In contrast, lymphocyte and T cell counts were increased significantly within one week prior to cyclosporine nephrotoxicity being diagnosed; the H/S ratio was not correlated with rejection or toxicity. These results indicate that H/S ratio is not associated with clinical events of renal allograft recipients, but serial lymphocyte and T cell subset counts can provide valuable information for the differentiation of rejection from cyclosporine nephrotoxicity, and also for predicting the outcome of the allograft rejection.

Enzyme-linked immunosorbent assay for serum renal tubular antigen in kidney transplant patients.

A mouse monoclonal antibody, specific for binding with the epithelial surface antigen in human renal proximal tubules, was produced by hybridoma culture. Using this antibody, an enzyme-linked immunosorbent assay was developed to measure the human renal tubular epithelial antigen (HRTE) concentrations in serum samples from 25 normal subjects and 66 consecutive renal allograft recipients. In 46 patients treated with azathioprine and prednisone, serum HRTE was elevated more than two-fold in 56 of 62 rejection episodes 2-5 days before the clinical diagnosis was made. Of the 56 rejection episodes, the antigen level fell to baseline after treatment in 44 steroid-responsive episodes, but it remained elevated in 8 steroid-resistant rejections, and it became undetectable 3-4 days after the initial elevation in 4 episodes in which allografts were lost to rejection. In 20 patients treated with cyclosporine and prednisone, all 25 rejection episodes demonstrated a greater than two-fold increase of serum HRTE 1-6 days prior to the diagnosis of rejection. The antigen level fell to baseline in 23 reversible rejection episodes, however serum HRTE remained elevated in 2 steroid-resistant patients whose grafts were lost to rejection. Cyclosporine nephrotoxicity without rejection was confirmed in 6 episodes, each of which demonstrated a more than two-fold increase in HRTE 2-4 days before toxicity was diagnosed. When the cyclosporine dose was reduced, the antigen level decreased as the serum creatinine declined. Serial determinations of serum HRTE in renal transplant recipients can provide valuable information for the early diagnosis and management of allograft rejection and cyclosporine nephrotoxicity.

U.S. nephrologists' attitudes towards renal transplantation: results from a national survey.

BACKGROUND: Renal transplantation is the optimal treatment for persons with end-stage renal disease (ESRD). A shortage of kidneys in the U.S. has focused increasing attention on the process by which kidneys are allocated. A national survey was undertaken to determine the relative importance of both clinical and nonclinical factors in the recommendation for renal transplantation by U.S. nephrologists. METHODS: We conducted a national random survey of 271 U.S. nephrologists using hypothetical patient scenarios to determine their recommendation for renal transplantation based on demographic, clinical, and social factors. Specifically, eight unique patient scenarios were randomly distributed to each survey respondent. RESULTS: According to responding nephrologists (response rate 53%), females were less likely than males to be recommended for renal transplantation [adjusted odds ratio (OR)=0.41; confidence interval (CI) 0.21, 0.79; for whites]. Asian males were less likely than white males to be recommended for transplantation (OR=0.46, CI 0.24, 0.91). Black-white differences in rates of recommendation were not found. Other factors associated with low rates of recommendation for renal transplantation included history of noncompliance (OR=0.17, CI 0.13, 0.23), <25% cardiac ejection fraction (OR=0.15, CI 0.10, 0.21), HIV infection (OR=0.01, CI 0.00, 0.01), and being >200 lbs (OR=0.73, CI 0.56, 0.95). CONCLUSIONS: Female gender, and Asian but not black race, were associated with a decreased likelihood that nephrologists would recommend renal transplantation for patients with end stage renal disease. The well-documented black-white disparities in use of renal transplantation may be due to unaccounted for factors or may arise at a subsequent step in the transplantation process.

Developing a health-related quality-of-life measure for end-stage renal disease: The CHOICE Health Experience Questionnaire.

The Choices for Healthy Outcomes in Caring for End-Stage Renal Disease ([ESRD] CHOICE) Study was designed to evaluate the effectiveness of alternative dialysis prescriptions. As part of CHOICE, we developed an instrument for measuring health-related quality of life (HRQOL) for patients with ESRD that would complement the Medical Outcomes Study 36-Item Short-Form Survey (SF-36) and be sensitive to differences in dialysis modality (hemodialysis [HD] and peritoneal dialysis [PD]) and dialysis dose. The selection of HRQOL domains to be included was based on: (1) a structured literature review of 47 articles describing 53 different instruments; (2) content analysis of five focus groups with HD and PD patients, nephrologists, and other providers; (3) a survey of 110 dialysis providers about features of different modalities that affect patient HRQOL; and (4) a semistructured survey of 25 patients with ESRD on the effects of dialysis on functioning and HRQOL. To help prioritize domains and items identified by these methods, a representative sample of 136 dialysis patients rated each item for frequency and bother. A panel of nephrologists provided advice about the salience of items to modality or dose. Items and scales were selected with a preference for existing measures tested in patients with ESRD and were tested for reliability and validity. The first four steps yielded 22 HRQOL domains that included 96 items: 8 generic domains in the SF-36 (health perceptions, physical, social, physical and emotional role function, pain, mental health, and energy); 8 additional generic domains (cognitive functioning, sexual functioning, sleep, work, recreation, travel, finances, and general quality of life); and 6 ESRD-specific domains (diet, freedom, time, body image, dialysis access [catheters and/or vascular], and symptoms). New items were developed or adapted to assess ESRD-specific domains. Scales for these items showed adequate internal consistency (Cronbach's alpha > 0.70, except for time [alpha = 0.57] and quality of life [alpha = 0.68]), as well as convergent and discriminant construct validity in a sample of 928 patients. The final questionnaire included 21 domains (time was deleted) and 83 items. We have designed a patient-centered instrument, the CHOICE Health Experience Questionnaire, that addresses domains that may be sensitive to differences in dialysis modality and dose and shows evidence for reliability and validity as a measure of HRQOL in ESRD.

Timing of nephrologist referral and arteriovenous access use: the CHOICE Study.

Recent clinical practice guidelines recommend the creation of an arteriovenous (AV) vascular access (ie, native fistula or synthetic graft) before the start of chronic hemodialysis therapy to prevent the need for complication-prone dialysis catheters. We report on the association of referral to a nephrologist with duration of dialysis-catheter use and type of vascular access used in the first 6 months of hemodialysis therapy. The study population is a representative cohort of 356 patients with questionnaire, laboratory, and medical record data collected as part of the Choices for Healthy Outcomes in Caring for End-Stage Renal Disease Center Study. Patients who reported being seen by a nephrologist at least 1 month before starting hemodialysis therapy (75%) were more likely than those referred later to use an AV access at initiation (39% versus 10%; P < 0.001) and 6 months after starting hemodialysis therapy (74% versus 56%; P < 0.01). Patients referred within 1 month of initiating hemodialysis therapy used a dialysis catheter for a median of 202 days compared with 64, 67, and 19 days for patients referred 1 to 4, 4 to 12, and greater than 12 months before initiating hemodialysis therapy, respectively (P trend < 0.001). Patients referred at least 4 months before initiating hemodialysis therapy were more likely than patients referred later to use an AV fistula, rather than a synthetic graft, as their first AV access (45% versus 31%; P < 0.01). These associations remained after adjustment for age, sex, race, marital status, education, insurance coverage, comorbid disease status, albumin level, body mass index, and underlying renal diagnosis. These data show that late referral to a nephrologist substantially increases the likelihood of dialysis-catheter use at the initiation of hemodialysis therapy and is associated with prolonged catheter use. Regardless of the time of referral, only a minority of patients used an AV access at the initiation of treatment, and greater than 25% had not used an AV access 6 months after initiation. Thus, further efforts to improve both referral patterns and preparation for dialysis after referral are needed.

US nephrologists' recommendation of dialysis modality: results of a national survey.

Selection of a dialysis modality for persons with end-stage renal disease (ESRD) has important lifestyle and occupational implications. The factors affecting modality choice remain unclear, resulting in a low rate of peritoneal dialysis (PD) in the United States compared with other countries. A national survey of 271 US nephrologists was conducted from June 1997 to June 1998 to assess the relative importance of nonclinical and clinical factors related to dialysis modality selection for patients with ESRD. Hypothetical patient scenarios were randomly assigned to nephrologists to determine their recommendation for dialytic therapy based on patient demographic, clinical, and social factors. US nephrologists were more likely to recommend PD for men with ESRD compared with women (39% versus 33%; P: < 0.05; adjusted odds ratio, 1.44; 95% confidence interval, 1.15 to 1.80), as well as for patients with good compliance (adjusted odds ratio, 11.80; 95% confidence interval, 9.29 to 15.01), weight less than 200 lb (adjusted odds ratio, 2.3; 95% confidence interval, 1.8 to 2.9), residual renal function (adjusted odds ratio, 2.14; 95% confidence interval, 1.71 to 2.70), absence of diabetes (adjusted odds ratio, 2.0; 95% confidence interval, 1.6 to 2.5), and living with family (adjusted odds ratio, 1.7; 95% confidence interval, 1.4 to 2.1). Nephrologists in practice for 11 or more years were less likely to recommend PD. The association of male sex with PD therapy suggests a potential bias or sensitivity to women's perception of body image. Race was not associated with PD recommendations after controlling for other demographic and clinical characteristics. Because the incident US ESRD population is increasingly characterized by factors associated with not selecting PD (diabetes, obesity, malnourishment, living alone, and substance abuse problems), our results suggest that PD use may decrease over time.

The political economy of nephrology.

An issue of Seminars devoted to "The Economics of Nephrology" requires consideration not only of the narrow economic issues affecting the specialty but also the public policies that establish its economic parameters. Some economic issues involve only the balancing of costs and revenues in a dialysis unit. Others turn on the ESRD policies of Medicare. Still others hinge on action by the US Congress and, by definition, are political in character. In nephrology, economics are intertwined with politics, hence the political economy of nephrology.

Structural changes following hypothermic preservation of human cadaveric kidneys.

Three kidneys preserved as though for transplantation became available for study. The clinical details relating to the donors and methods of preservation by simple hypothermia and pulsatile perfusion are presented. Light microscopic and ultrastructural features observed following perfusion fixation of the kidneys are described. All three kidneys showed some reversible ischemic cell damage, but only one showed evidence of ischemic cell damage that was considered to be irreversible. The latter was seen focally in the pars recta of the proximal convoluted tubules and in the ascending thick limb of the loop of Henle. The irreversible changes were present in the kidney that had undergone the longest period of simple hypothermic storage prior to transfer to pulsatile perfusion preservation. The similarity of the findings to those seen in vivo in the rat after one hour of total renal ischemia, followed by 24 hours' reflow, is discussed; a hypothesis is suggested to explain the site of the irreversible injury seen in the kidneys under study.

Patient profile and effect of dietary therapy on post-transplant hyperlipidemia.

The effect of dietary therapy on the serum lipid profile was examined in 32 post-transplant patients. Patients were transplanted more than 4 months before the study and had stable renal function and no other condition affecting lipid metabolism. Serum lipid profiles were determined on two serum samples obtained after a 12-hour fast. Seventeen patients who had pre-transplant hyperlipidemia (HLP) had similar HLP after transplantation. Of the 14 patients with normal pre-transplant profiles, 9 remained normal and 5 developed HLP. Twelve patients with HLP received out-patient dietary therapy providing less than 500 mg of cholesterol, less than 35% of calories from fat, less than 50% of calories from carbohydrate, and a P:S ratio greater than 1. Maintenance calories were based on the Harris-Benedict standard except for 9 overweight patients who were given less. After 3 months of therapy, serum cholesterol and triglycerides decreased to normal in 8 of 9 patients in whom both were elevated before dietary treatment and were unchanged in one patient. In 3 patients who had normal triglyceride but elevated cholesterol levels before therapy, cholesterol decreased but remained above normal; triglyceride increased in one patient and remained normal in two. High-density lipoprotein cholesterol (HDL-C) increased in all 12 patients and became normal in 11. Body weight fell in 11 of 12 patients receiving dietary therapy. Cholesterol, triglyceride, and HDL-C remained unchanged in 11 patients who did not undergo dietary treatment. Dietary therapy is a safe and effective way to treat post-transplant HLP.

Measuring and improving the health status of end stage renal disease patients.

This highlight reports on recent efforts to develop and promote health status measurement instruments for use in dialysis units that treat end-stage renal disease (ESRD) patients, most of whom are covered for all medical services under Medicare. Readers interested in a more detailed discussion of instruments, including associated data collection and data processing aspects, should consult a recently published account, with its extensive references, of four instruments currently being used in dialysis units (Rettig et al., 1997). Those interested in early reports of the clinical utility of such instruments should consult the following references (Kurtin et al., 1992; Meyer et al., 1994; and DeOreo, 1997).

Use of focus groups to identify concerns about dialysis. Choice Study.

BACKGROUND: Patients with end-stage renal disease (ESRD) may have quality-of-life (QOL) concerns that are not fully appreciated by their providers. The authors conducted focus groups with dialysis patients and dialysis professionals to determine whether this qualitative method would reveal differences between patients' and providers' views about: 1) domains of QOL that are affected by ESRD and dialysis; and 2) aspects of dialysis that affect QOL. METHODS: Separate focus group discussions were held with: 8 adult hemodialysis patients (mean age 50 years; 3 women; mean duration of dialysis 8.5 years), 5 adult peritoneal dialysis patients (mean age 54 years; 3 women; mean duration of dialysis 4.6 years), 8 nephrologists (mean of 12 years of dialysis practice), and 9 other health professionals involved in dialysis care (3 nurses, 2 dietitians, 2 social workers, and 2 technicians; mean of 10 years experience in dialysis care). Discussions were audiotaped, transcribed verbatim, and reviewed independently by three investigators to identify and categorize distinct thoughts. RESULTS: 1,271 distinct thoughts were identified and grouped into 20 related categories, which included ten QOL domains and ten aspects of dialysis that affect QOL. Compared with the professionals, the patients identified one additional relevant QOL domain (10 vs 9), and one additional aspect of dialysis that affects QOL (10 vs 9), and expressed more thoughts per domain (p < 0.05), although the contents of their comments were frequently similar. Among QOL domains, the numbers of related thoughts identified by patients and professionals, respectively, were: freedom/control (60, 89); social relationships (36, 11); anxiety (37, 4); role function (24, 10); energy (12, 10); body image (16, 4); sex (11, 21); mental attitude (21, 0); sleep (15, 1), and cognitive function (13, 7). Among aspects of dialysis that affect QOL, the numbers of thoughts identified by patients and professionals were: general dialysis issues (159, 105); relationships with staff (62, 110); patient education (63, 68); diet (44, 40); scheduling (57, 3); vascular or peritoneal access issues (31, 17), adaptation to dialysis (16, 14); dialysis dose (18, 8); symptoms (25, 0), and self-care (5, 24). CONCLUSIONS: Although health professionals have a good understanding of patient concerns about the effects of ESRD and dialysis, the focus group discussions revealed a breadth and depth of QOL concerns that they may not fully appreciate.