Social/economic costs and health-related quality of life in patients with juvenile idiopathic arthritis in Europe.

OBJECTIVE: The aim of this study was to determine the economic burden from a societal perspective and the health-related quality of life (HRQOL) of patients with juvenile idiopathic arthritis (JIA) in Europe. METHODS: We conducted a cross-sectional study of patients with JIA from Germany, Italy, Spain, France, the United Kingdom, Bulgaria, and Sweden. Data on demographic characteristics, healthcare resource utilization, informal care, labor productivity losses, and HRQOL were collected from the questionnaires completed by patients or their caregivers. HRQOL was measured with the EuroQol 5-domain (EQ-5D-5L) questionnaire. RESULTS: A total of 162 patients (67 Germany, 34 Sweden, 33 Italy, 23 United Kingdom, 4 France, and 1 Bulgaria) completed the questionnaire. Excluding Bulgarian results, due to small sample size, country-specific annual health care costs ranged from €18,913 to €36,396 (reference year: 2012). Estimated direct healthcare costs ranged from €11,068 to €22,138; direct non-healthcare costs ranged from €7837 to €14,155 and labor productivity losses ranged from €0 to €8715. Costs are also shown to differ between children and adults. The mean EQ-5D index score for JIA patients was estimated at between 0.44 and 0.88, and the mean EQ-5D visual analogue scale score was estimated at between 62 and 79. CONCLUSIONS: JIA patients incur considerable societal costs and experience substantial deterioration in HRQOL in some countries. Compared with previous studies, our results show a remarkable increase in annual healthcare costs for JIA patients. Reasons for the increase are the inclusion of non-professional caregiver costs, a wider use of biologics, and longer hospital stays.

Takayasu's arteritis: A study of 104 Italian patients.

OBJECTIVE: Takayasu's arteritis (TA) is a rare vasculitis. The Italian Takayasu's Arteritis study group was established with the aim to describe a large cohort of patients. METHODS: Data were collected by means of an ad hoc form. Demographic information, clinical history, vascular findings, treatment, risk factors, and comorbidities were analyzed. RESULTS: Data of 104 patients were collected. The median delay in diagnosis was 15.5 months (range 0-325 months). Age at onset <15 years was associated with a higher probability, whereas elevated erythrocyte sedimentation rate with a lower probability, of a delay in diagnosis. The majority of patients experienced nonspecific signs and symptoms indicative of an inflammatory disease in the early phase. Among vascular involvement, stenosis was the most frequent lesion, being present in 93% of patients, followed by occlusion (57%), dilatation (16%), and aneurysm (7%). Glucocorticoids were the mainstay of treatment in our series; however, treatment with cytotoxic agents was required in about half of the patients. Fifty-two patients underwent at least 1 surgical procedure. The main indications for intervention were renal vascular hypertension, cerebral hypoperfusion, and limb claudication. CONCLUSION: As with many rare diseases, delay in diagnosis is an important issue for patients with TA. The increasing occurrence of vascular lesions along with the disease progression put to question the long-term effectiveness of contemporary treatment. These data may be helpful in increasing physicians' awareness to prevent diagnosis delay, update guidelines, and plan future research projects.

Immunosuppressive treatment for idiopathic membranous nephropathy in adults with nephrotic syndrome.

BACKGROUND: Idiopathic membranous nephropathy (IMN) is the most common form of nephrotic syndrome in adults. The disease shows a benign or indolent course in the majority of patients, with a rate of spontaneous complete or partial remission of nephrotic syndrome as high as 30% or more. Despite this, 30-40% of patients progress toward end-stage renal failure (ESRF) within 5-15 years. OBJECTIVES: To assess the benefits and harms of immunosuppressive treatment for IMN in adults. SEARCH STRATEGY: We searched the Cochrane Renal Group Specialised Register (December 2003), The Cochrane Central Register of Controlled Trials (CENTRAL) (Cochrane Library Issue 4, 2003), MEDLINE and Pre-MEDLINE (1966 - December 2003), EMBASE (1980 - December 2003), reference lists of nephrology textbooks, review articles, prospective trial registers, relevant trials and abstracts from nephrology scientific meetings and the internet without language restriction. We also contacted principal investigators of controlled studies. SELECTION CRITERIA: Randomised controlled trials (RCTs) and quasi-RCTs comparing any immunosuppressive interventions for the treatment of IMN in adults. DATA COLLECTION AND ANALYSIS: Two reviewers independently assessed and extracted information. Information was collected on method, participants, interventions and outcomes (death, ESRF, proteinuria, serum creatinine, GRF, remission, adverse events). MAIN RESULTS: A total of 18 trials with 1025 patients were included. No differences were found when we combined data of all treatment categories as a group and compared them with placebo or no treatment. Oral glucocorticoids. No beneficial effect on any of the end points chosen for efficacy was observed. Alkylating agents showed a significant beneficial effect on complete remission (RR 2.37, 95%CI 1.32 to 4.25, P = 0.004) but not on partial remission (RR 1.22, 95%CI 0.63 to 2.35, P = 0.56) or complete or partial remission (RR 1.55, 95%CI 0.72 to 3.34, P = 0.27). Cyclophosphamide treatment resulted in significantly lower rate of discontinuations due to adverse events as compared to chlorambucil (RR 2.34, 95%CI 1.25 to 4.39, P = 0.008). There was no evidence of clinically relevant differences in favour of cyclosporin and there was insufficient data on anti-proliferative agents. REVIEWERS' CONCLUSIONS: This review failed to show any long-term effect of immunosuppressive treatment on patient and/or renal survival. There was an increased number of discontinuations due to adverse events in immunosuppressive treatment groups. Within the class of alkylating agents there is weak evidence supporting the efficacy of cyclophosphamide as compared to chlorambucil. On the other hand, cyclophosphamide had fewer side effects leading to patient withdrawal than chlorambucil.

Proteinuria and its consequences in renal disease.

UNLABELLED: Chronic renal diseases that involve proteinuria are typically characterized by an inexorable progression to end-stage renal failure. Many studies suggest that this progression may be the result of factors, such as intraglomerular hypertension and glomerular hypertrophy, that are unrelated to the initial disease. This paper reviews the mechanisms of progression of chronic renal diseases and discusses therapeutic strategies that should prevent or minimize further renal damage and the applicability of these strategies to patients with the rare X-linked lysosomal storage disorder Fabry disease. Renal involvement is a major feature of Fabry disease, which is characterized by vacuolated epithelial cells in the glomerulus and distal tubules, resulting from lipid inclusions within these cells. Although enzyme replacement therapy is the key strategy to halt the progression of Fabry disease, additional therapeutic options include blood pressure control, reduction of proteinuria, lipid control and inhibition of the renin-angiotensin system. CONCLUSION: A range of therapeutic options, used in conjunction with enzyme replacement therapy, may have beneficial effects on the renal manifestations of Fabry disease.

Modulating the profit motive to meet needs of the less-developed world.

The success, despite the problems, of academic/industrial collaborations over the past decade owes much to the profit motive. However, market-driven research and development has little to offer patients in the less-developed world. Some flexibility has already been demonstrated on drugs for orphan (rare or under-researched) diseases. Many diseases in less-developed countries are not rare. Academic researchers should be encouraging the establishment of funding for basic and clinical research that is directed at patients' needs in the less-developed world and that is independent of a commercial ethos.

Progression, remission, regression of chronic renal diseases.

The prevalence of chronic renal disease is increasing worldwide. Most chronic nephropathies lack a specific treatment and progress relentlessly to end-stage renal disease. However, research in animals and people has helped our understanding of the mechanisms of this progression and has indicated possible preventive methods. The notion of renoprotection is developing into a combined approach to renal diseases, the main measures being pharmacological control of blood pressure and reduction of proteinuria. Lowering of blood lipids, smoking cessation, and tight glucose control for diabetes also form part of the multimodal protocol for management of renal patients. With available treatments, dialysis can be postponed for many patients with chronic nephropathies, but the real goal has to be less dialysis-in other words remission of disease and regression of structural damage to the kidney. Experimental and clinical data lend support to the notion that less dialysis (and maybe none for some patients) is at least possible.

Mycophenolate mofetil for the treatment of Takayasu arteritis: report of three cases.

BACKGROUND: Takayasu arteritis is a rare form of chronic inflammatory disease of the large arterial vessels. Some patients do not respond to steroids or immunosuppressant drugs. OBJECTIVE: To evaluate the effect of mycophenolate mofetil in patients with severe Takayasu arteritis. DESIGN: Case series. SETTING: Clinical Research Center for Rare Diseases in Bergamo, Italy. PATIENTS: Three patients with Takayasu arteritis. INTERVENTION: Mycophenolate mofetil (2 g/d) given orally in two divided doses. MEASUREMENTS: Clinical evaluation and assessment of leukocyte counts were done weekly. Vascular lesions were assessed by using Doppler ultrasonography. RESULTS: All patients showed clinical benefit, and two resumed work after months of inactivity. Patients were also able to taper and discontinue steroid use. Mycophenolate mofetil was well tolerated, and no signs of toxicity were observed. CONCLUSIONS: Mycophenolate mofetil may be an alternative to steroids and cytotoxic agents in patients with Takayasu arteritis. Before results of controlled trials become available, mycophenolate mofetil should be considered only for patients who do not improve or stabilize with conventional therapy.

The first clinical and epidemiological programme on renal disease in Bolivia: a model for prevention and early diagnosis of renal diseases in the developing countries.

BACKGROUND: The prevalence and incidence of renal diseases in developing countries are not known. This lack of knowledge is an obstacle to the adoption of preventive measures which may be of great value in a social and economic environment where treatment options for end-stage renal failure are simply not available to the vast majority of the population. Urinalysis, a simple and inexpensive test, remains a cornerstone in the evaluation of the kidney and may also be easily employed in mass screening for renal abnormalities in a developing country. METHODS: An educational campaign on renal diseases was conducted in three selected areas of Bolivia. Urine samples were collected and sent to one of 21 participating clinical centers. Fresh urine specimens were screened using a dipstick for chemical analysis and by microscopic urinalysis after centrifugation. In those patients in whom urinary abnormalities were found, further investigations were carried out in order to define the diagnosis; these patients were enrolled in a 3-year follow-up program. RESULTS: Apparently healthy subjects (n = 14,082) were referred to the First Clinical and Epidemiological Program of Renal Diseases from rural and metropolitan areas in Bolivia. Urinary abnormalities were detected in 4261 subjects at first screening. The most common form of urinary abnormality was hematuria, which was found in 2010 (47% of positively screened subjects). Other renal abnormalities were leukocyturia (41%) and proteinuria (11%). Confirmatory tests and further clinical studies were then carried out in 1019 people. On a second screening 35% of the subjects had no urinary abnormalities; in the remaining people the following diagnosis were made: asymptomatic urinary-tract infection (48.4%), isolated benign hematuria (43.9%), chronic renal failure (1.6%), renal tuberculosis (1.6%). Other diagnosis were: renal stones 1.3%, diabetic nephropathy 1% and polycystic kidney diseases 1.9%. CONCLUSIONS: This study helped define for the first time the frequency of asymptomatic renal diseases in Bolivia. It shows that it is possible to screen a large population of patients at relatively low cost, providing the framework for further action that may help in the prevention and timely diagnosis of renal diseases.

Recent developments in the management of membranous nephropathy.

Idiopathic membranous nephropathy is one of the most commonly encountered forms of nephrotic syndrome in adults. The natural history of the disease, observed in a small sample of untreated patients, reveals that a large proportion of patients experience spontaneous remission, whereas approximately one third of them progress towards renal insufficiency, and thus require dialysis. Hence, several attempts to treat this condition have been investigated and several protocols, based on different combinations of corticosteroids and/or immunosuppressive agents, have been proposed. However, none of these protocols has been uniformly adopted by renal physicians, either because of no or limited efficacy of most of them, or due to the potential of short- and long-term untoward effects. In this review, we examine the available data on the natural course of the disease and the possibility of identifying clinical and laboratory characteristics that could help to predict the course of membranous nephropathy. We also summarise the results of the most relevant clinical trials, and offer an updated meta-analysis of treatment studies, including the latest data on cyclosporin.

Treatment of idiopathic membranous glomerulopathy.

The treatment of membranous nephropathy, the most common form of glomerular diseases causing nephrotic syndrome in adults, is still debated. A considerable percentage of patients have a spontaneous remission of the disease and reduction of urinary protein excretion with time. Studies in the past have indicated that prednisone may have beneficial effects, but this has not been confirmed by more recent investigation. Others have studied the association of methylprednisolone with cyclophosphamide or chlorambucil, but results are conflicting. The main reasons for the conflicting data are the variety of clinical presentations of the disease and the different study populations. Most trials performed so far have not included enough patients in each category to adequately detect differences between treatment groups and placebo groups. Several studies with few numbers of patients reported that cyclosporine effectively reduced proteinuria and may have less long-term toxicity than more conventional immunosuppressants. This finding, however, must be verified by appropriate clinical trials.

Prognosis of untreated patients with idiopathic membranous nephropathy.

BACKGROUND: Defining the most appropriate treatment for patients with idiopathic membranous nephropathy is a matter of controversy. The course of the disorder is often benign, and the immunosuppressive regimens used in some patients have uncertain benefits and substantial risks. We studied the natural history of idiopathic membranous nephropathy in patients who received only symptomatic therapy. METHODS: We prospectively studied 100 consecutive patients (68 men and 32 women; mean [+/- SD] age, 51 +/- 17 years) with biopsy-proved idiopathic membranous nephropathy. The patients received diuretic or antihypertensive drugs as needed, but no glucocorticoid or immunosuppressive drugs. We examined the patients and measured their urinary protein excretion and serum creatinine concentrations every 6 months for a mean of 52 months. RESULTS: Twenty-four (65 percent) of the 37 patients followed for at least five years had complete or partial remission of proteinuria; in 6 others (16 percent), end-stage renal disease developed, and they required dialysis. As calculated by the Kaplan-Meier method, the estimated probability (+/- the standard error of the estimate) of retaining adequate kidney function was 88 +/- 5 percent after five years and 73 +/- 7 percent after eight years. The prognosis was poorer in men and in patients over 50 years of age, but not in patients with the nephrotic syndrome, hypertension, or hypercholesterolemia. CONCLUSIONS: Most untreated patients with idiopathic membranous nephropathy maintain renal function for prolonged periods and are likely to have spontaneous remission. These results do not support the use of glucocorticoids and immunosuppressive drugs in patients with idiopathic membranous nephropathy.

Analysis by fast atom bombardment mass spectrometry of phospholipids from tubuli, glomeruli, and urine of normal rats and rats with acute renal failure.

Fast atom bombardment mass spectrometry was used to characterize phospholipids from tubuli and glomeruli of normal rats and rats with acute renal failure. It was possible to assess the molecular species of the principal phospholipidic classes. In all of them, the most abundant species contained a residue of arachidonic acid. The phospholipids of urine were also analyzed, showing the presence of the major molecular species of several phospholipid classes. Excretion of phospholipids was greater in urine from rats with acute renal failure.

Renal function at hospital admission as a prognostic factor in adult hemolytic uremic syndrome. The Italian Registry of Haemolytic Uremic Syndrome.

The clinical records of adult patients with a diagnosis of hemolytic uremic syndrome were retrospectively reviewed with the aim of evaluating the long-term outcome of renal function. The setting is the Italian Registry of Haemolytic Uraemic Syndrome, with which 13 Nephrology Centers have participated. Clinical and laboratory data of 43 patients with hemolytic uremic syndrome were evaluated. The mean age at onset was 34.3 +/- 18.3 yr. Men and women were equally affected. No seasonal trend in presentation was observed. In 20 patients, hemolytic uremic syndrome was primitive, whereas in 23, it was associated with another disease (cancer, preeclampsia, malignant hypertension, vasculitides). Gastrointestinal symptoms were the most frequently observed prodromes. Thirty (70%) patients required dialysis during the acute phase of the disease. Six patients died during the acute phase of the disease, and one died later after discharge (overall mortality, 16%). After 1 yr of follow-up, 11 (26%) patients had recovered a normal renal function, 14 (33%) had hypertension and/or renal insufficiency, and 11 (26%) were on regular dialysis. When prognostic factors of survival and recovery of renal function were considered, it was found that older age was associated with higher mortality in the acute phase, whereas severe renal involvement at the onset of the disease (as expressed by elevated serum creatinine) was associated with a long-term unfavorable prognosis.

Nature and extent of glomerular injury induced by cyclosporine in heart transplant patients.

We sought to clarify whether low-dose cyclosporine (5.0 +/- 2.2 mg/kg/day) given for more than two years to prevent cardiac graft rejection induced glomerular injury and to quantify the extent of the lesions. After renal hemodynamic studies, renal biopsy specimens were obtained from 10 patients on cyclosporine and analyzed by a novel morphometric technique consisting of a tridimensional reconstruction of the glomerular tuft. Autopsy kidney specimens from three patients with no clinical history of renal disease, and from four patients who died with dilatative cardiomyopathy served as controls. The glomerular filtration rate and renal plasma flow were significantly depressed below normal values in transplant recipients given cyclosporine, averaging 35 +/- 8 and 325 +/- 94 ml/min/1.73 m2, respectively. Conventional light microscopy of specimens from controls and from patients who died with dilatative cardiomyopathy did not reveal renal structural abnormalities. By contrast kidney specimens from cyclosporine-treated patients had obliterative arteriolopathy and ischemic-type changes, with thickening and wrinkling of glomerular capillary wall. Morphometrical analysis of 28 control glomeruli and 40 glomeruli from patients with dilatative cardiomyopathy showed glomerular capillary tuft volumes (VCT) ranging between 1.2 and 2.3 microns 3 x 10(-6), whereas of 102 glomeruli from cyclosporine-treated patients 42.1% had VCT lower than 1.2 microns 3 x 10(-6) and 24.4% VCT higher than 2.3 microns 3 x 10(-6).(ABSTRACT TRUNCATED AT 250 WORDS)