Withdrawal from dialysis: a palliative care perspective.

A retrospective chart review was conducted in this pilot study of 35 patients who withdrew from dialysis and were followed by a palliative care team. Data included etiology of end-stage renal disease, comorbid illnesses, mode of dialysis and duration, survival time after withdrawal, reason for withdrawal, mental competency, symptom management, and the nature of death. Mean survival time was 10 days. The most frequent symptoms following withdrawal were confusion, agitation, pain and dyspnea. 1/3 of the sample were cognitively impaired at the time of the withdrawal decision. 17% experienced suffering during the withdrawal period, 24% had unrelieved symptoms, 19% psychological distress, while just over 1/3 of patients died alone. With the provision of palliative care, symptom prevalence in the last 24 hours dropped from 53 to 20% for pain, 68 to 33% for agitation and 46 to 26% for dyspnea. Opioids and benzodiazepines were used in the treatment of over 90% of patients. Palliative medicine has the potential to improve the care of patients who discontinue dialysis.

Failure of chelation therapy in lead nephropathy.

A patient with lead nephropathy and gout was treated with three months of edetic acid chelation. The therapy resulted in normalization of a previously abnormal result of edetic acid lead mobilization test. Nevertheless, progressive renal insufficiency occurred. At autopsy, an increased bone lead content was documented, suggesting that the edetic acid lead mobilization test may underestimate total body lead stores and that chelation therapy may not be effective in reversing advanced lead nephropathy. Alternatively, a longer period of therapy may be necessary to remove lead stores. More studies are needed to determine the relationship between the results of the edetic acid test and bone lead stores. Methods other than the edetic acid lead mobilization test should be considered to monitor the adequacy of treatment in lead nephropathy.

Increased osmolal gap in alcoholic acidosis.

We studied a patient with alcoholic acidosis and an increased osmolal gap. Ethyl alcohol and other compounds that are known to increase serum osmolality in alcoholics were not detected. However, the levels of glycerol, acetone, and the acetone metabolites acetol and 1,2-propanediol were increased in the serum of this patient. On admission and 3 and 7 hours after admission, the combined serum osmolality of glycerol, acetone, acetol, and 1,2-propanediol accounted for 48%, 92%, and 62% of the increase in the osmolal gap above the highest normal level of 10 mOsm/kg H2O. The disappearance of the osmolal gap correlated with the correction of the acidosis and the concomitant reduction in serum glycerol and acetone levels. Elevations of endogenous glycerol, acetone, and acetone metabolite levels should now be added as causes for an increased osmolal gap in the alcoholic patient. Ingestion of toxic alcohols can no longer be assumed to be the only cause for an increased osmolal gap in alcoholic patients.

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.

Syndrome of inappropriate antidiuresis in Waldenström's macroglobulinemia.

Hyponatremia due to the syndrome of inappropriate antidiuresis rather than due to isotonic hyponatremia from hyperproteinemia developed in a patient with Waldenström's macroglobulinemia. The patient was unable to excrete a water load normally despite suppression of antidiuretic hormone to normal levels. The temporal relationship between control of the tumor and resolution of the hyponatremia suggests that the tumor either produced a substance that enhanced the hydro-osmotic effect of endogenous antidiuretic hormone or produced an antidiuretic substance immunologically different from antidiuretic hormone. The syndrome of inappropriate antidiuresis should be suspected in hyponatremic patients with Waldenström's macroglobulinemia.

Transplantation and 2-year follow-up of kidneys procured from a cadaver donor with a history of lupus nephritis.

BACKGROUND: Two patients underwent cadaver transplantation with kidneys from a donor with a history of World Health Organization Class IV/V lupus nephritis, and we report their clinical and pathological outcome. METHODS: The donor had a diagnosis of lupus nephritis made by renal biopsy 5 years before donation. At the time of donation, a biopsy was performed on the donor and on one of the recipients at 2 months and 1 year after the transplant. RESULTS: Both recipients underwent uneventful renal transplantation. On the first postoperative day, the donor's final pathological results became available. Although the frozen section seemed to be quite benign, the permanent sections revealed World Health Organization Class II/V lupus nephritis, with full house immunofluorescence and multiple electron dense deposits. Biopsies were performed on recipient #2 at 8 weeks and 1 year after the transplant. These revealed marked diminution followed by complete resolution of all tubular reticular structures and deposits as well as immunofluorescent activity. Both recipients remain with normal renal function and urinalysis at 3 years after the transplant. CONCLUSION: Although a history of clinically significant renal disease has been considered an absolute contraindication to kidney donation, with appropriate workup and caution, select patients may still be considered, which would increase the potential donor pool.

The effects of lipid-lowering agents on acute renal allograft rejection.

BACKGROUND: Preliminary results from clinical trials suggest that 3-hydroxy-3-methylglutaryl co-enzyme A reductase inhibitors may help prevent acute renal allograft rejection. However, the mechanism for this putative effect of 3-hydroxy-3-methylglutaryl co-enzyme A reductase inhibitors, and whether it is independent of lipid-lowering per SE are unknown. METHODS: Immediately after renal transplantation we randomly allocated (proportioned 2:1:2) patients to: 1) simvastatin (10 mg/day, n=53), 2) simvastatin placebo plus gemfibrozil (dose adjusted for renal function, n=36), and 3) simvastatin placebo (n=52). RESULTS: Simvastatin, but not gemfibrozil, reduced total and low density lipoprotein cholesterol during the first 90 days posttransplant. There were no major adverse effects of therapy. However, there were no effects of treatment on acute rejection. Indeed, survival free of acute rejection at 90 days was 72% in the simvastatin group, 72% in the gemfibrozil group, and 77% in the placebo control group (P=0.771). A post hoc power analysis suggested that there was only a 7.5% chance that a true effect of simvastatin on acute rejection (versus placebo) was not detected, and a 2.5% chance that an effect of gemfibrozil on acute rejection (versus placebo) was not detected in this study. CONCLUSION: Lipid-lowering agents may not reduce the incidence of acute renal allograft rejection. However, additional studies are needed to confirm this observation. In the mean time, many if not most renal transplant recipients should be treated with HMG-CoA reductase inhibitors starting early posttransplant to prevent cardiovascular disease complications. The results of this study suggest that starting lipid-lowering therapy immediately after renal transplantation is both safe and effective in lowering total and low density lipoprotein cholesterol.

Changing incidence of glomerular diseases in adults.

Studies performed at large metropolitan medical centers have reported an increasing incidence of idiopathic focal segmental glomerulosclerosis (FSGS) in adults. To determine whether a similar trend occurs in small urban and rural communities and to determine the role of race in these observations, we reviewed the patient records of all adults who underwent renal biopsies at our institution over the 20-year period from 1974 to 1994. The patients were grouped for analysis in 5-year intervals, 1975 to 1979, 1980 to 1984, 1985 to 1989, and 1990 to 1994, for the following diagnoses: FSGS, membranous nephropathy (MN), minimal change nephropathy (MCN), membranoproliferative glomerulonephritis (MPGN), immunoglobulin A (IgA) nephropathy, chronic glomerulonephritis, diabetic nephropathy, hypertensive nephrosclerosis, and chronic interstitial nephritis. Patients with secondary causes for these lesions were excluded. The relative frequency of FSGS increased from 13.7% during 1975 to 1979 to 25% during 1990 to 1994 (P < 0.05). The relative frequency of MN decreased from 38.3% during 1975 to 1979 to 14.5% during 1990 to 1994 (P < 0.01). There were no changes in the frequencies of MCN, MPGN, IgA nephropathy, chronic glomerulonephritis, diabetic nephropathy, hypertensive nephrosclerosis, or chronic interstitial nephritis over the 20-year period. However, there was a significant increase in the percentage of blacks with FSGS, from 0% in 1975 to 1979 to 22.6% in 1990 to 1994, and an increased percentage of Hispanics with FSGS, from 0% in 1975 to 1979 to 21.3% in 1990 to 1994 (P < 0.05). The modest increase in whites with FSGS did not reach statistical significance. The incidence of MN in blacks and whites decreased over the 20-year period. In the last 5 years, 15 patients per year had FSGS compared with 7 patients per year with MN (P < 0.05). No changes in age or sex between groups or over time accounted for these results. We conclude that FSGS is now diagnosed twice as often as MN and is the most common idiopathic glomerular disease at our hospital. Reasons for this increase include the emergence of FSGS in both Hispanics and blacks, with a modest increase of FSGS in whites. The increase in FSGS in the three most common races in our community suggests that factors other than genetic, perhaps environmental, have a role in the pathogenesis of FSGS.

Hemodynamic, cardiac, and electrolyte effects of low-dose aerosolized terbutaline sulfate in asthmatic patients.

STUDY OBJECTIVE: Aerosolized beta2-agonists have been associated with increased morbidity in asthmatics. These drugs cause transient increases in heart rate and decreases in serum potassium levels after these drugs are first utilized. This study is designed to elucidate whether beta-adrenergic tolerance to the hemodynamic, cardiac, and electrolyte effects of inhaled terbutaline occurs during 14 days of maintenance therapy. DESIGN: Eight patients with stable asthma weaned off beta2-agonist therapy were studied in a randomized, double-blinded, placebo-controlled study utilizing aerosolized terbutaline, 400 microg q6h. Hemodynamic measurements and M-mode echocardiography were performed before and 15 and 30 min after the initial dose of terbutaline or placebo and after a dose of aerosolized terbutaline after 14 days of aerosolized terbutaline maintenance therapy. Holter monitors were worn on the first day of placebo or terbutaline therapy and on day 14 of terbutaline therapy. Plasma potassium, bicarbonate, and glucose levels, pH, renin activity, and serum insulin and aldosterone levels were measured before and after 24 and 48 h after terbutaline or placebo therapy and after 14 days of aerosolized terbutaline maintenance therapy. RESULTS: Terbutaline increased cardiac index and decreased systemic vascular resistance greater after 14 days of therapy compared with the first dose (5.2+/-0.5 vs 4.4+/-0.6 L/min/m2; p<0.05; and 760+/-62 vs 1,016+/-118 dyne x s x cm(-5), p<0.01). After 14 days of terbutaline therapy, the mean maximum heart rate and number of episodes of heart rate > 100 beats/min were higher compared with the other study day (p<0.05). Plasma potassium level decreased from 4.29+/-0.09 to 3.65+/-0.16 mmol/L after 24 h of terbutaline and to 3.90+/-0.11 mmol/L after 48 h. Plasma potassium level returned to baseline after 14 d of terbutaline therapy. Plasma glucose and serum insulin levels rose significantly 24 h and 48 h after terbutaline and returned to baseline after 14 d of terbutaline therapy. Serum aldosterone level decreased significantly as serum potassium level decreased in the first 48 h of terbutaline therapy but returned to baseline levels after 14 d of terbutaline. CONCLUSIONS: Cardiovascular beta2-receptors in patients with stable asthma do not develop tolerance to the effects of low-dose aerosolized terbutaline after 14 days of maintenance therapy. In contrast, the homeostatic mechanisms regulating serum potassium develop tolerance to low-dose terbutaline maintenance therapy. Lack of cardiovascular tolerance to maintenance doses of aerosolized beta2-agonists may be important in increased morbidity if excessive amounts of these drugs are administered during asthma exacerbations.

Capsulectomy: a cure for the page kidney.

Hypertension is a known complication after renal trauma. The cause of posttraumatic hypertension can be renal scarring, infarction, hydonephrosis, infection, vascular injury, and parenchymal compression. The authors report on the case of a 16-year-old boy who experienced hypertension after blunt renal trauma. He had a dense fibrous pseudocapsule causing renal parenchymal compression, which lead to hypertension, a Page kidney. Evaluation with computed tomographic (CT) scan, radioisotope renal scan, renal Doppler, and angiogram confirmed the diagnosis. Removal of the renal capsule and the constricting fibrous pseudocapsule was curative.

Simplification of an erythropoiesis model for design of anemia management protocols in end stage renal disease.

Many end stage renal disease (ESRD) patients suffer from anemia due to insufficient endogenous production of erythropoietin (EPO). The discovery of recombinant human EPO (rHuEPO) over 30 years ago has shifted the treatment of anemia for patients on dialysis from blood transfusions to rHuEPO therapy. Many anemia management protocols (AMPs) used by clinicians comprise a set of experience-based rules for weekly-to-monthly titration of rHuEPO doses based on hemoglobin (Hgb) measurements. In order to facilitate the design of an AMP based on formal control design methods, we present a physiologically-relevant erythropoiesis model, and show that its nonlinear dynamics can be approximated using a static nonlinearity, a step that greatly simplifies AMP design. We demonstrate applicability of our results using clinical data.

Pulmonary hemorrhage and acute renal failure in a patient with mixed connective tissue disease.

Mixed connective tissue disease (MCTD) is considered to have a benign clinical course. Recently, renal disease has been recognized as a frequent complication (20%). This report describes a patient with MCTD who developed pulmonary hemorrhage and acute renal failure. The renal biopsy, in addition to a long-standing membranous nephropathy, revealed a tubulointerstitial nephritis. Immunofluorescent and electron microscopy showed immune complex deposition along the tubular basement membrane. Life-threatening, immune complex-mediated events can occur in the course of MCTD, manifested as pulmonary hemorrhage and tubulointerstitial nephritis.

Renal disease in cryoglobulinemia type II: response to therapy. A case report and review of the literature.

A case of cryoglobulinemia type II with membranoproliferative glomerulonephritis and vasculitis is described. Clinically and serologically the patient responded to cyclophosphamide and prednisone therapy. This correlated with improvement in the glomerular and interstitial lesions on renal biopsy specimens, although skin and renal vasculitis persisted over a 2-year period. These observations suggest important differences in the immunopathologic mechanisms involved in the vascular versus glomerular injury. Infiltration of macrophages were demonstrated in the glomerular capillary lumen while polymorphonuclear cells predominated in the vascular lesion. The presence of macrophages in the glomerular capillary lumen correlated with clinical proteinuria. A review of the literature also suggests that cyclophosphamide in combination with prednisone appears to be an effective therapeutic regimen for the glomerulonephritis of cryoglobulinemia. However, the correlation of clinical response and renal morphology in cryoglobulinemia has heretofore not been emphasized.

Impaired potassium and magnesium homeostasis in acute tubulo-interstitial nephritis.

Although acute tubulo-interstitial nephritis is increasingly recognized as a cause of acute renal failure, little is known about renal tubular function in this disease. We report on two patients with acute tubulo-interstitial nephritis who demonstrated abnormalities in proximal and distal tubular function. The first patient developed hyperkalemia presumably from a potassium secretory defect in the distal nephron. The second patient developed an incomplete Fanconi's syndrome with glycosuria and aminoaciduria and two heretofore unreported complications of acute interstitial nephritis: hypokalemia and hypomagnesemia secondary to urinary losses of these cations. Careful monitoring of renal tubular function is indicated in patients with acute tubulo-interstitial nephritis.