International variation in dialysis discontinuation in patients with advanced kidney disease.

BACKGROUND: Decisions about dialysis for advanced kidney disease are often strongly shaped by sociocultural and system-level factors rather than the priorities and values of individual patients. We examined international variation in the uptake of conservative approaches to the care of patients with advanced kidney disease, in particular discontinuation of dialysis. METHODS: We employed an observational cohort study design using data collected from patients maintained on long-term hemodialysis between 1996 and 2015 in facilities across 12 developed countries participating in the Dialysis Outcomes and Practice Patterns Study (DOPPS). The main outcome was discontinuation of dialysis therapy. We analyzed the association between several patient characteristics and time to dialysis discontinuation by country and phase of study entry. RESULTS: A total of 259 343 DOPPS patients contributed data to the study, of whom 48 519 (18.7%) died during the study period. Of the decedents, 5808 (12.0%) discontinued dialysis before death. Rates of discontinuation were higher within the first few months after initiation of dialysis, among older adults, among those with a greater number of comorbidities and among those living in an institution. After adjustment for age, sex, dialysis duration, diabetes and dialysis era, rates of discontinuation were highest in Canada, the United States and Australia/New Zealand (33.8, 31.4 and 21.5 per 1000/yr, respectively) and lowest in Japan and Italy (< 0.1 per 1000/yr). Crude discontinuation rates were highest in dialysis facilities that were more likely to offer comprehensive conservative renal care to older adults. INTERPRETATION: We found persistent international variation in average rates of dialysis discontinuation not explained by differences in patient case-mix. These differences may reflect physician-, facility- and society-level differences in clinical practice. There may be opportunities for international cross-collaboration to improve support for patients with end-stage renal disease who prefer a more conservative approach.

Imaging appearance of fibrosing diseases of the retroperitoneum: can a definitive diagnosis be made?

PURPOSE: To assess the frequency with which previously reported characteristic findings of retroperitoneal fibrosis (RPF) (a circumferential or almost circumferential peri-aortic mass centered at L4, which does not displace the abdominal aorta or proximal common iliac arteries) are present in patients with RPF, in patients with other fibrosing diseases, and in cancer patients referred to a subspecialty clinic with a suspected diagnosis of RPF, in order to determine whether diagnostic percutaneous biopsy can be avoided in some patients. METHODS: This HIPAA-compliant Institutional Review Board-approved retrospective study assessed clinical and CT and MR imaging abnormalities on imaging studies in 92 patients referred to a subspecialty clinic with suspected RPF over a 14-year period. Two reviewers, in consensus, determined the frequency of different CT and MRI findings in three groups of patients (Group 1: those with an eventual diagnosis of RPF, Group 2: those with a fibrosing disease associated with vascular or urologic abnormalities, and Group 3: those with cancer). Assessed imaging features included the presence of retroperitoneal masses, whether masses were single or multiple, whether such masses were circumferential or nearly circumferential, whether they displaced the aorta away from the spine (with the degree of such displacement measured), and whether there were abnormalities outside of the peri-aortic region of the retroperitoneum. The frequency with which findings previously reported as characteristic of RPF were present was determined for each of the three groups. Imaging results were correlated with the final diagnoses. RESULTS: Of 68 subjects eventually diagnosed with retroperitoneal fibrosis (RPF) (Group 1), 47 had peri-aortic retroperitoneal masses, 18 of which displaced the aorta anteriorly away from the spine. Of 12 subjects with fibrosing abnormalities related to vascular or urologic disease (Group 2), six had retroperitoneal masses, none of which displaced the aorta away from the spine. Of 12 subjects with malignancies (Group 3), six had peri-aortic retroperitoneal masses only two of whom had aortic displacement. Only 34 of 68 Group 1 subjects had peri-aortic masses characteristic of RPF, compared with six Group 2 subjects and one Group 3 subject. Subjects with characteristic retroperitoneal masses were significantly more likely to have benign disease than cancer (p = 0.009). CONCLUSION: Many patients with RPF do not have characteristic imaging findings. Contrary to prior publications, absence of aortic displacement is not seen in all patients with RPF and is seen in some cancer patients. Nonetheless, when infiltrative peri-aortic retroperitoneal soft tissue that does not displace the aorta is encountered on CT or MRI, RPF can be diagnosed with a high degree of confidence, obviating the need for biopsy.

Coronary artery involvement in idiopathic retroperitoneal fibrosis: computed tomographic findings.

We describe 2 patients with perivascular low-attenuation soft tissue and inflammatory changes surrounding the coronary arteries in the clinical setting of idiopathic retroperitoneal fibrosis. Neither patient had inducible ischemia on cardiac stress testing. The coronary arteries present an additional site of interest as connections between sclerosing diseases--including retroperitoneal fibrosis, fibrosing mediastinitis, autoimmune pancreatitis, sclerosing cholangitis, and other entities--continue to emerge.

Responses of human skin in organ culture and human skin fibroblasts to a gadolinium-based MRI contrast agent: comparison of skin from patients with end-stage renal disease and skin from healthy subjects.

OBJECTIVE: Nephrogenic systemic fibrosis is a clinical syndrome occurring in a small subset of patients with end-stage renal disease (ESRD). Exposure to certain of the gadolinium-based contrast agents during magnetic resonance imaging appears to be a trigger. The pathogenesis of the disease is largely unknown. The present study addresses potential pathophysiologic mechanisms. MATERIALS AND METHODS: We have compared responses in organ-cultured skin and skin fibroblasts from individuals with ESRD to responses of healthy control subjects to Omniscan treatment. RESULTS: Treatment of skin from ESRD patients with Omniscan stimulated production of matrix metalloproteinase-1 and tissue inhibitor of metalloproteinases-1, but not type I procollagen. The same treatment also stimulated an increase in hyaluronan production. Similar results were seen with skin from normal controls but basal levels were higher in ESRD patients. Fibroblasts in monolayer culture gave the same responses, but there were no differences based on whether the cells were isolated from the skin of healthy subjects or those with ESRD. CONCLUSION: These data indicate that Omniscan exposure alters an enzyme/inhibitor system responsible for regulating collagen turnover in the skin and directly stimulates hyaluronan production. The higher basal levels of type I procollagen, matrix metalloproteinase-1, tissue inhibitor of metalloproteinases-1, and hyaluronan in the skin from ESRD patients could contribute to the sensitivity of this patient population to fibrotic changes, which might be induced by exposure to some of the gadolinium-based contrast agents.

Collagenolytic activity is suppressed in organ-cultured human skin exposed to a gadolinium-based MRI contrast agent.

OBJECTIVE: Human skin produces increased amounts of matrix metalloproteinase-1 (MMP-1) when exposed in organ culture to Omniscan, one of the gadolinium-based MRI contrast agents (GBCA). MMP-1, by virtue of its ability to degrade structural collagen, contributes to collagen turnover in the skin. The objective of the present study was to determine whether collagenolytic activity was concomitantly up-regulated with increased enzyme. MATERIALS AND METHODS: Skin biopsies from normal volunteers were exposed in organ culture to Omniscan. Organ culture fluids obtained from control and treated skin were examined for ability to degrade type I collagen. The same culture fluids were examined for levels of MMP-1, tissue inhibitor of metalloproteinases-1 (TIMP-1), and complexes of MMP-1 and TIMP-1. RESULTS: Although MMP-1 was increased in culture fluid from Omniscan-treated skin, there was no increase in collagenolytic activity. In fact, collagenolytic activity declined. Increased production of TIMP-1 was also observed in Omniscan-treated skin, and the absolute amount of TIMP-1 was greater than the amount of MMP-1. Virtually all of the MMP-1 was present in MMP-1-TIMP-1 complexes, but the majority of TIMP-1 was not associated with MMP-1. When human dermal fibroblasts were exposed to TIMP-1 (up to 250 ng/mL), no increase in proliferation was observed, but an increase in collagen deposition into the cell layer was seen. CONCLUSION: Gadolinium-based MRI contrast agent exposure has recently been linked to a fibrotic skin condition in patients with impaired kidney function. The mechanism is unknown. The increase in TIMP-1 production and concomitant reduction in collagenolytic activity demonstrated here could result in decreased collagen turnover and increased deposition of collagen in lesional skin.

Idiopathic retroperitoneal fibrosis: a review of the pathogenesis and approaches to treatment.

Idiopathic retroperitoneal fibrosis (IRPF) is an increasingly recognized syndrome. The development of inflammation and fibrosis in the retroperitoneum most often results in a periaortic mass on computed tomography or magnetic resonance imaging that causes pain and constitutional symptoms. Its organ involvement results in urinary tract obstruction, bowel dysfunction, and venous compression with leg swelling, or thrombosis. The syndrome appears autoimmune in nature, but has no specific immunologic markers. However, nonspecific inflammatory indicators, such as sedimentation rate and C-reactive protein level, reflect disease activity and therapeutic response. Retroperitoneal fibrosis also can arise secondary to inflammatory, infectious, or malignant disease in retroperitoneal organs, in which case treatment is directed at the primary process. However, in patients with IRPF, initial treatment of the local mechanical complications must be followed by medical therapy with corticosteroids or, more recently, the addition of steroid-sparing agents. Although there are no controlled therapeutic trials, a number of reports with as few as 3 or as many as 28 cases describe sustained and effective steroid-sparing treatment with cyclophosphamide, azathioprine or colchicine, or such newer agents as mycophenolate mofetil or tamoxifen. Overall, IRPF responds to corticosteroid therapy initially but recurs without prolonged treatment. Sustained remission can be attained with steroid-sparing treatment. Kidney function can be preserved, and local organ dysfunction can remit for periods of 10 years or more. Although not randomized or controlled, the evidence convincingly supports a combination of initial surgical or urological intervention, along with early corticosteroid therapy for up to 6 months followed by either mycophenolate or tamoxifen for 1 to 3 years. What was previously believed to be an uncommon and challenging syndrome can be treated successfully when recognized by its characteristic presentation.

Effects of gadolinium-based magnetic resonance imaging contrast agents on human skin in organ culture and human skin fibroblasts.

OBJECTIVE: Nephrogenic systemic fibrosis (NSF) is a clinical syndrome linked with exposure in renal failure patients to gadolinium-based magnetic resonance imaging contrast agents (GBCAs). The pathogenesis of the disease is largely unknown. The present study addresses potential pathophysiological mechanisms. MATERIALS AND METHODS: Here, we have examined human skin in organ culture and human dermal fibroblasts in monolayer culture for responses to GBCA stimulation. RESULTS: Treatment of normal human skin in organ culture with Omniscan had no significant effect on type I procollagen but increased both matrix metalloproteinase-1 and tissue inhibitor of metalloproteinases-1. At the histologic level, many interstitial cells demonstrated cytologic features characteristic of activation (ie, light staining, oblong, plump nuclei). Omniscan, as well as 3 other magnetic resonance imaging contrast agents (Magnevist, Multihance, and Prohance), increased proliferation of human dermal fibroblasts in monolayer culture. Increased proliferation was accompanied by an increase in production of both matrix metalloproteinase-1 and tissue inhibitor of metalloproteinases-1 but no increase in type I procollagen. Concentrations required for effects differed among the 4 agents (Omniscan < Magnevist and Multihance < Prohance). In contrast to its effects on fibroblast function, Omniscan did not stimulate human epidermal keratinocyte proliferation when examined over a wide range of concentrations. CONCLUSION: These data provide evidence that GBCA exposure in ex vivo skin from healthy individuals increases fibroblast proliferation and has effects on the enzyme/inhibitor system that regulates collagen turnover in the skin.

Patient-staff interactions and mental health in chronic dialysis patients.

Chronic dialysis imposes ongoing stress on patients and staff and engenders recurring contact and long-term relationships. Thus, chronic dialysis units are opportune settings in which to investigate the impact of patients' relationships with staff on patient well-being. The authors designed the present study to examine the degree to which perceptions of open communication between patients and staff affect patient mental health. A one-year, two-wave longitudinal survey assessed patient (N = 109) perceptions of the interpersonal environment and mental health. Assessments included sharing personal information (open disclosure), assisting one another (helping), staff respect for patients (respect), and hierarchical patient-staff relations (formal staff authority). Cross-sectional and longitudinal regression analyses examined how these characteristics of the interpersonal environment relate to depression and subjective well-being among patients. Multivariate analysis showed that open disclosure correlated independently with lower levels of depression at baseline (N = 109) and a predicted significant decrease in depression over time (N = 64). Other interpersonal characteristics did not correlate with depression or subjective well-being at baseline or longitudinally. The interpersonal climate in chronic dialysis units influences patient well-being. Contrary to traditional views, open disclosure in patients' relationships with staff is not detrimental and contributes to well-being.

Nephrogenic systemic fibrosis: a report of 29 cases.

OBJECTIVE: The purpose of this study was to determine the incidence of nephrogenic systemic fibrosis and its relation to renal failure and the administration of gadolinium-based contrast material at an academic medical center. MATERIALS AND METHODS: A dermatopathology database was searched to identify patients in whom nephrogenic systemic fibrosis was diagnosed. The medical records of these patients were reviewed. Renal function concurrent with any administration of gadolinium-based contrast material was assessed, as was patient outcome. A database of patients undergoing long-term dialysis was reviewed separately to determine how many had received gadolinium and the frequency of nephrogenic systemic fibrosis among these patients. RESULTS: Twenty-nine patients were found to have had nephrogenic systemic fibrosis between November 15, 1999, and December 31, 2006. It was known that gadolinium-based contrast material had been administered to 25 of these patients before diagnosis. All 29 patients had compromised renal function (27 had chronic renal failure, and two had acute renal failure). Determination of the temporal relation between gadolinium-based contrast administration and symptom onset often was difficult. Only eight patients had severe morbidity. Nephrogenic systemic fibrosis developed in 12 (2.9%) of 414 patients undergoing long-term dialysis who received gadolinium-based contrast material. CONCLUSION: We confirm the strong association between nephrogenic systemic fibrosis and gadolinium-based contrast administration. Although the use of high doses of gadolinium and the occurrence of chronic renal failure have been implicated in other reports, several of our patients received standard doses of gadolinium, and two had transient acute renal failure before diagnosis. Most patients had mild or moderate symptoms. Nephrogenic systemic fibrosis developed in 2.9% of patients undergoing long-term dialysis who received gadolinium-based contrast material but in none of the long-term dialysis patients who did not receive gadolinium-based contrast material.

Predictors of postoperative acute renal failure after noncardiac surgery in patients with previously normal renal function.

BACKGROUND: The authors investigated the incidence and risk factors for postoperative acute renal failure after major noncardiac surgery among patients with previously normal renal function. METHODS: Adult patients undergoing major noncardiac surgery with a preoperative calculated creatinine clearance of 80 ml/min or greater were included in a prospective, observational study at a single tertiary care university hospital. Patients were followed for the development of acute renal failure (defined as a calculated creatinine clearance of 50 ml/min or less) within the first 7 postoperative days. Patient preoperative characteristics and intraoperative anesthetic management were evaluated for associations with acute renal failure. Thirty-day, 60-day, and 1-yr all-cause mortality was also evaluated. RESULTS: A total of 65,043 cases between 2003 and 2006 were reviewed. Of these, 15,102 patients met the inclusion criteria; 121 patients developed acute renal failure (0.8%), and 14 required renal replacement therapy (0.1%). Seven independent preoperative predictors were identified (P < 0.05): age, emergent surgery, liver disease, body mass index, high-risk surgery, peripheral vascular occlusive disease, and chronic obstructive pulmonary disease necessitating chronic bronchodilator therapy. Several intraoperative management variables were independent predictors of acute renal failure: total vasopressor dose administered, use of a vasopressor infusion, and diuretic administration. Acute renal failure was associated with increased 30-day, 60-day, and 1-yr all-cause mortality. CONCLUSIONS: Several preoperative predictors previously reported to be associated with acute renal failure after cardiac surgery were also found to be associated with acute renal failure after noncardiac surgery. The use of vasopressor and diuretics is also associated with acute renal failure.

Effect of time on sensitivity and specificity of access flow in predicting thrombosis.

Dialysis access monitoring may help decrease thrombosis-related morbidity. We investigated the effect of time elapsed since an access flow measurement on test accuracy of a novel flow monitoring method called variable flow (VF) Doppler. A retrospective review was conducted in 36 patients with prosthetic grafts for vascular access using access thrombosis as the clinical endpoint. Receiver operator characteristic (ROC) curves and test sensitivity and specificity were determined for various follow-up time intervals. ROC analysis showed increasing test discrimination for shorter time intervals. Sensitivity and specificity for a commonly used surveillance threshold (600 ml/min) showed specificity that was little changed (88-93%) from follow-up time intervals of 15 days to 6 months. However, sensitivity was low (21%) at 6 months, increased to 50% at 2 months, 67% at 1 month, and 100% at 15 days (a single event). Low access blood flow using VF Doppler predicts near-term thrombosis. These data further imply that the discriminative value of access flow monitoring appears to be highly dependent on time from the flow measurement, improving with shorter time intervals from the measurement.

Palliative care in chronic kidney disease: peer mentoring program personalizes advance directives discussions.

Medical professionals in nephrology are trained to think about improving quality and quantity of life with their patients, but only recently are they being urged to consider ways to improve end-of-life care. For many staff, this still feels contradictory. One nephrologist recently told these authors, "I was trained to help people live, not to help them die." The RWJF Promoting Excellence in End-of-Life Care work group has investigated, accumulated, and designed resources to help renal teams improve in this challenging arena. Peer mentoring is one such powerful resource, and, once in operation, is cost free. In conjunction with renal social work and the renal team, peer mentoring is a wonderful program that can decrease anxiety and preserve caring relationships in our burgeoning dialysis communities.

Nephrogenic fibrosing dermopathy: a novel cutaneous fibrosing disorder in patients with renal failure.

BACKGROUND: Nephrogenic fibrosing dermopathy is a newly recognized cutaneous fibrosing disorder marked by the acute onset of induration involving the upper and lower limbs in patients with acute or chronic renal failure. The etiology, pathogenesis, associated clinical conditions (other than renal failure), and ultimate course have not been defined in the few cases studied. Presently, there is no effective treatment, and the condition persists in most patients. METHODS: Clinical and histopathologic data on 13 patients from our institution with the diagnosis of nephrogenic fibrosing dermopathy were reviewed. Several clinical and laboratory parameters were examined to see if any were consistently associated with the disease. Biopsy specimens were analyzed to determine if there was a pattern to the evolution of fibrosis in these patients. RESULTS: All 13 patients had renal failure before disease onset: 8 were undergoing chronic hemodialysis, 2 were undergoing chronic peritoneal dialysis, and 3 with acute renal failure had never undergone dialysis before the development of dermopathy. Most patients had other serious underlying medical conditions. Many patients were taking erythropoietin, cyclosporine, or both before the onset of disease. In transplant patients, no histocompatibility antigens were found to be associated with the disease. There were various laboratory abnormalities, but none were consistently associated with the condition. In skin biopsy specimens taken 7 to 180 days after disease onset, there were histopathologic changes suggestive of a tissue reaction to injury, as well as the development of smooth muscle actin-positive myofibroblasts. CONCLUSION: Nephrogenic fibrosing dermopathy is a novel cutaneous fibrosing disorder that is distinguished from other sclerosing or fibrosing skin disorders by distinctive clinical and histopathologic findings occurring in the setting of renal failure. There were no additional clinical risk factors or laboratory findings common to the 13 patients studied, other than renal failure. The resemblance to a tissue injury reaction and the presence of myofibroblasts in the tissue specimens suggest that fibrogenic cytokines may be involved in the evolution of the disease.