Michael J. Germain

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.

Factors explaining the intention to give blood among the general population

Background and Objectives  The aim of this study was to identify factors explaining the intention to donate blood.

Executive summary of the KDIGO Controversies Conference on Supportive Care in Chronic Kidney Disease: developing a roadmap to improving quality care

Patients with advanced chronic kidney disease (CKD) have a high burden of physical and psychosocial symptoms, poor outcomes, and high costs of care. Current paradigms of care for this highly vulnerable population are variable, prognostic and assessment tools are limited, and quality of care, particularly regarding conservative and palliative care, is suboptimal. The KDIGO Controversies Conference on Supportive Care in CKD reviewed the current state of knowledge in order to define a roadmap to guide clinical and research activities focused on improving the outcomes of people living with advanced CKD, including those on dialysis. An international group of multidisciplinary experts in CKD, palliative care, methodology, economics, and education identified the key issues related to palliative care in this population. The conference led to a working plan to address outstanding issues in this arena, and this executive summary serves as an output to guide future work, including the development of globally applicable guidelines.

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.

A Longitudinal Study of Uremic Pruritus in Hemodialysis Patients

BACKGROUND AND OBJECTIVES Although uremic pruritus (UP) is a highly prevalent complication of chronic kidney disease, it remains poorly characterized. There have been no longitudinal studies of natural history, and no health-related quality of life (HR-QOL) instruments have been developed for UP. The objectives of this study were to describe the natural history of UP, to compare rating scales of itching intensity, and to assess usefulness and validity of HR-QOL instruments for UP. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS The intensity, severity, and effects of pathologic itching on HR-QOL were assessed prospectively in 103 patients with UP on chronic hemodialysis. Outcome measures were obtained at scheduled intervals over 3.5 months. RESULTS Itching daily or nearly daily was reported by 84% of patients and had been ongoing for >1 year in 59%. In 83%, pruritus involved large, nondermatomal areas with striking bilateral symmetry. Two thirds of the patients were using medications such as antihistamines, steroids, and various emollients without satisfactory relief of itching. Statistically significant associations were found among itching intensity, severity, and HR-QOL measures in domains such as mood, social relations, and sleep. Among patients with moderate-to-severe UP, changes in itching intensity of 20% or greater were associated with significant reductions in HR-QOL measures. CONCLUSIONS This first longitudinal study of UP describes key features of UP and its effect on HR-QOL. The assessment instruments we have developed are easily used, are responsive to changes in UP intensity, and should facilitate clinical evaluation and research to meet the needs of afflicted patients.

Denying the Dying Advance: Directives and Dialysis Discontinuation

A structured interview was administered to a sample of patients on maintenance dialysis and their attending physicians to obtain information on the documentation of their end-of-life treatment preferences. The majority of the patients reported never having considered stopping dialysis, or having discussed with their nephrologist or family the circumstances in which treatment should be discontinued. Only 7 patients (6%) had completed an advance directive; these patients were all men (P = 0.01) and tended to be better educated (P = 0.02). Only one of the nine physicians had completed an advance directive. In most cases, the dialysis patients and their treatment team staff were preoccupied with the struggles of daily life and had avoided or denied considerations of terminal illness and death. The literature on denial, medical illness, and dying is also reviewed as it relates to dialysis patients, end-of-life treatment, and terminal care.

The Renal Palliative Care Initiative.

Despite ongoing technological advances, patients with end-stage renal disease (ESRD) have a mortality rate of approximately 23% per year, and comorbid cardiovascular, cerebrovascular, and peripheral vascular disorders often make life on dialysis an ordeal. This patient population needs an improved approach to symptom assessment and control, as well as advance care planning and high-quality palliative care. Families need support during the lifetime and after the death of their loved ones. To address these needs, the Renal Palliative Care Initiative (RPCI) was instituted at Baystate Medical Center, a large tertiary care hospital, and at eight dialysis clinics in the Connecticut River Valley. With the cooperation of a large nephrology practice, the Western New England Renal and Transplant Associates, a core group of physicians, nurses, and social workers were trained in palliative medicine, and charged with the goals of developing and implementing innovative interventions. The RPCIs programs include symptom management protocols, advance care planning, and bereavement services for families and staff. The Initiative is increasing completion of formal advance directives by the patient population, while staff and families are particularly pleased with annual renal memorial services. The RPCI experience has much to offer the practice of nephrology, and it is relevant to ongoing efforts to extend palliative medicine beyond the traditional focus on cancer and AIDS.

Trough serum vancomycin levels predict the relapse of gram-positive peritonitis in peritoneal dialysis patients.

We reviewed 31 episodes of gram-positive peritonitis that occurred in our peritoneal dialysis population between 1990 and 1993 in an attempt to identify the risk factor(s) for peritonitis relapse. All patients were treated with 4 weekly doses of intravenous vancomycin. Vancomycin doses no. 1 and 2 were based on body weight (15 mg/kg with a 1-g minimum); vancomycin doses no. 3 and 4 were adjusted in an attempt to maintain the trough serum vancomycin level at greater than 12 mg/L. Nine peritonitis episodes complicated by a relapse were identified. Peritonitis episodes preceding a relapse were similar to relapse-free episodes with respect to patient age, diabetes, peritoneal dialysis modality, duration of peritoneal dialysis treatment, residual urea clearance, peritoneal fluid cell count, causative organism, and weekly vancomycin dose. However, cumulative 4-week mean trough vancomycin levels were consistently lower during peritonitis episodes preceding a relapse (7.8 +/- 0.6 mg/L during relapse-prone episodes v 13.7 +/- 0.9 mg/L during relapse-free episodes; P = 0.0004). Furthermore, relapses developed during nine of 14 peritonitis episodes demonstrating a 4-week mean trough vancomycin level less than 12 mg/L compared with zero of 17 episodes with a 4-week trough level greater than 12 mg/L (P < 0.05). The detection of a low initial 7-day trough vancomycin level also was a useful marker for subsequent peritonitis relapse. In 13 peritonitis episodes associated with an initial trough level less than 9 mg/L, nine were complicated by a relapse.(ABSTRACT TRUNCATED AT 250 WORDS)

Withholding and Withdrawal from Dialysis: What We Know About How Our Patients Die

Withholding and withdrawal of dialysis has been a reality since dialysis was invented. Only in the past 20 years has it been formally studied, and we still have a great deal to learn. The nephrology community has slowly come to accept that, for some of our patients, not having dialysis is a better option than continuing or initiating therapy. The principles of palliative care throughout the disease trajectory and hospice care at end of life are germane to this population due to its high symptom burden and mortality rate. We review what is currently known concerning patients who choose to withhold or withdraw from dialysis, and the current barriers (and solutions) to providing them with optimal palliative care.

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.