Determinants of renal and patient outcomes in a Spanish cohort of patients with ANCA-associated vasculitis and renal involvement.

The classification of anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) remains controversial. The main objective of this study was to define the respective values of ANCA serotype-based classification, clinicopathological classification, and histopathological classification in predicting patient and renal outcomes in a Spanish cohort of patients with ANCA with specificity for myeloperoxidase, MPO-ANCA, versus ANCA with specificity for proteinase 3, PR3-ANCA. Two hundred and forty-five patients with ANCA-AAV and biopsy-proven renal involvement diagnosed between 2000 and 2104 were recruited in 12 nephrology services. Clinical and histologic data, renal outcomes, and mortality were analyzed. We applied the Chapel Hill Consensus Conference definition with categories for granulomatosis with the polyangiitis (GPA) and microscopic polyangiitis (MPA), the classification based on ANCA specificity, and the histopathological classification proposed in 2010. Eighty-two percent were MPO-ANCA positive and 18.0% PR3-ANCA positive. Altogether, 82.9% had MPA and 17.1% GPA. The median follow-up was 43.2 months (0.1-169.3). Neither ANCA-based serological nor clinical classification was predictive of renal outcomes or patient survival on bivariate or multivariate Cox regression analysis. Histopathological classification was found to predict development of end-stage renal disease (p = 0.005) in Kaplan-Meier analysis. ANCA specificity was more predictive of relapse than clinicopathological classification in multivariate analysis (HR 2.086; 95% CI 1.046-4.158; p = 0.037). In our Spanish cohort, a majority of patients had an MPO-ANCA-AAV. A classification based on ANCA specificity has a higher predictive value for relapse occurrence and could be used for decision-making with respect to induction treatment and maintenance therapies.

[On the Issue of Register of Patients of Gynecological Profile with Anemia Syndrome].

The abundant menorrhagia is the most prevalent cause of iron-deficient conditions in women. Though diagnostic of anemia is a simple task deficiency of knowledge in the area of hematology favors spreading and aggravation of anemia processes. The implementation of the register of patients with anemia syndrome into practical activities of physicians of all specialties is a modern direction of studying the given pathology. The proposed system of management of treatment diagnostic process permitted to optimize data collection related to disease, to ameliorate diagnostic search and to rationalize treatment of patients.

[Renal failure stages as predictors of mortality following acute coronary syndrome]. / El grado de insuficiencia renal como predictor de mortalidad tras un síndrome coronario agudo.

INTRODUCTION: renal glomerular filtration rate on hospital admission in patients presented with an acute coronary syndrome as a predictor for mortality. PATIENTS AND METHODS: The study analysed 290 patients admitted on hospital with an acute coronary syndrome during one year (2003). Renal function was estimated using the renal glomerular filtration rate by the MDRD formula. Patients were stratified in three groups: patients with a GFR > or = 60 ml/min/1,73 m2; n = 186, patients with GFR < 60 or > 30; n = 93 and patients with GFR < 30; n = 11. RESULTS: 66.6% of patients were males and 66.5% were older than 65 years old. 54.5% suffered from hypertension and 39% were diabetics. All patients with GFR < 30 ml/min had an acute coronary syndrome without elevation of ST segment. They were the oldest with a major proportion of previous cardiovascular events as cerebrovascular disease, peripheral vascular disease or myocardial infarction. Diagnostic procedures and treatments were less administered in patients with GFR < 30 ml/min. Although in the univariate analysis demonstrated that hospital mortality was related to GFR < 30 ml/min, sex, ageing, Killip > 1, ventricular function and cTnT elevation, only GFR < 30 ml/min, ageing, heart failure and ventricular dysfunction persisted significant in the multivariate analysis. Hospital mortality was 27.3% in patients with GFR < 30 ml/min, 7.5% in patients with GFR between 30-60 ml/min and 3.8% in patients with a GFR > or = 60 ml/min. Mortality after two years follow up was 27.3% in patients with GFR < 30 ml/min, 20.4% in patients with GFR between 30-60 ml/min and 10.2% in patients with a GFR > or = 60 ml/min. Mortality (hospital mortality and after two years of follow up) was increased in patients with GFR< 30 ml/min, ageing, heart failure and diabetes after adjusted for other prognostic factors. CONCLUSIONS: A reduced glomerular filtration rate is an independent risk factor for mortality in patients with an acute coronary syndrome. Estimation of the renal glomerular filtration rate might be used as prognostic value in these patients.

Conversion from calcineurin inhibitors to sirolimus in kidney transplant patients reduces the urinary transforming growth factor-beta1 concentration.

INTRODUCTION: Chronic allograft dysfunction (CAD) is the main cause of late transplant failure. Although several etiologies have been postulated, toxicity for calcineurin inhibitors (CNIs) is one of the most important causes of CAD, characterized by arteriolar hyalinosis, luminal narrowing, increased glomerulosclerosis, and tubulointerstitial damage. It's known that in transplant patients with CAD, fibrogenic mediators such as transforming growth factor beta (TGF-beta) are increased. Sirolimus is an immunosuppressive agent with a distinct mechanism of action compared with CNI. AIM: This study assessed variations in levels of fibrogenic mediators among CAD patients treated with CNIs, before and after conversion to sirolimus. PATIENTS AND METHODS: We studied twelve renal transplant patients with CAD on CNI treatment. TGF-beta in plasma and urine, endothelin-1, and vascular endothelial growth factor (VEGF) were studied before and 8 months after conversion to sirolimus treatment. RESULTS: TGF-beta urine levels decreased from 24.7 +/- 11.2 to 12.8 +/- 5.1 ng/24 h (P = .049). In plasma, a similar decrease trend was observed (22.2 +/- 32 to 10.3 +/- 3 ng/mL), although it was not significant (P = .079). Endothelin-1 showed a decrease (8.1 +/- 3 to 5.2 +/- 1.1 pmol/L; P = .1) and VEGF in plasma increased from 34.3 +/- 37 to 92.2 +/- 86 pg/mL (P = .051). CONCLUSIONS: Patients undergoing conversion from CNI to sirolimus treatment for CAD presented a significant decrease in TGF-beta urine levels, representing a decreased mediator of the CAD fibrogenic process.

[Peritoneal implants in patients affected by chronic renal failure in hemodialysis programme]. / Implantes peritoneales en pacientes con insuficiencia renal crónica en programa de hemodiálisis.

The presence of peritoneal implants detected by computered axial tomography (CT) is usually related to mesothelial primary neoformative processes or, more frequently to peritoneal metastasis or peritoneal carcinomatosis. Although the higher prevalence of neoplastic processes in the chronic renal failure population, the association of peritoneal implants and constitutional syndrome is not always correlated to peritoneal carcinomatosis. We present the case of two patients with chronic renal failure in hemodialysis programme, with abdominal insidious clinical, constitutional syndrome and similar peritoneal implants seen by CAT: the histologic analysis of peritoneal implants gave the definitive diagnostic of secondary amyloidosis and peritoneal tuberculosis respectively.

[Anti-glomerular basement membrane antibody mediated disease: revision of 32 cases and follow-up at one year of the diagnosis]. / Enfermedad por Ac anti-MBG: revisión de 32 casos y seguimiento al año del diagnóstico.

Anti-basement membrane antibody mediated disease is an unfrequent entity but with a high mortality and morbidity. We present a revision of 32 patients diagnosed of anti-basement membrane antibody mediated disease between 1983 and 1997, and their evolution at one year of the diagnosis. The clinical pattern of presentation was as a Goodpasture's syndrome (glomerulonephritis and lung haemorrhage) in 15 patients and glomerulonephritis without lung involvement in 17. We reviewed retrospectively the features at the clinical presentation, the different treatments, and the delay of the starting of it since the beginning of the symptoms, in order to evaluate a prognosis dats of the disease. After the retrospective study we deduce that anti-basement membrane antibody mediated disease has a high mortality although the different regimes of treatment applied (25%), and the need of renal replacement therapy at one year of diagnosis is also high (70.8%). The renal survival at one year of the diagnosis is low and the response to therapy depends on the serum creatinine value at the diagnosis. The contribution of immunocompetent leucocytes to renal hypercellularity suggests that both humoral and cell-mediated immunity play a role in this disease.

Henoch-Schönlein IgA glomerulonephritis complicating myeloma kidneys: case report.

Myeloma kidney is the principal pathological substrate of rapidly progressive renal failure in multiple myeloma. We report the unusual case of a 72-year-old male diagnosed with kappa Bence Jones myeloma with renal failure which needed dialysis. After treatment with vincristine, doxorubicin (Adriamycin), dexamethasone (VAD), and plasmapheresis, the renal function was recovered until serum creatinine level was <2 mg/dl. Six months later, the pathological counterpart of rapidly progressive renal failure was crescentic IgA proliferative glomerulonephritis as a manifestation of Henoch-Schönlein syndrome associated with sepsis caused by coagulase-negative staphylococci. This case suggests that mesangial IgA deposition should be considered within the spectrum of consequent glomerular lesion-associated chemotherapy occurring in multiple myeloma.

[Acute kidney failure as the clinical presenting form of renal Burkitt's lymphoma in an HIV-positive patient]. / Fracaso renal agudo como forma de presentación clínica de linfoma de Burkitt renal en un paciente HIV positivo.

Burkitt's lymphoma is a tumour often associated with low immunity as acute lymphoblastic leukaemia (l3) or infection by the human immunodeficiency virus (HIV). The incidence of renal affection is variable (34-62%) and there are different aetiologies. We present a case of acute renal failure in a patient with a Burkitt's lymphoma and renal infiltration, and infected by the human immunodeficiency virus.

Serum cystatin C as a new marker for noninvasive estimation of glomerular filtration rate and as a marker for early renal impairment.

Cystatin C is a nonglycosylated basic protein produced at a constant rate by all investigated nucleated cells. It is freely filtered by the renal glomeruli and primarily catabolized in the tubuli (not secreted or reabsorbed as an intact molecule). Because serum cystatin C concentration is independent of age, sex, and muscle mass, it has been postulated to be an improved marker of glomerular filtration rate (GFR) compared with serum creatinine level. We compared serum cystatin C level with other markers of GFR, such as serum creatinine level and creatinine clearance, and analyzed their variations based on iothalamate labeled with iodine 125 ((125)I-iothalamate) clearance ((125)I-ICl), used as the gold standard for GFR. The concentrations of the two different markers of GFR in patients with impaired renal function were classified according to (125)I-ICl. Twenty individuals with normal renal function ((125)I-ICl, 128 +/- 23 mL/min/1.73 m(2)) were used as the control group. Serum cystatin C level showed a greater sensitivity (93.4%) than serum creatinine level (86.8%). Also, serum cystatin C showed the greatest proportion of increased values in patients with impaired renal function (100%) compared with serum creatinine level (92.15%). Serum cystatin C levels started to increase to greater than normal values when GFR was 88 mL/min/1.73 m(2), whereas serum creatinine level began to increase when GFR was 75 mL/min/1.73 m(2). These data suggest that measurement of serum cystatin C may be useful to estimate GFR, especially to detect mild reductions in GFR, and therefore may be important in the detection of early renal insufficiency in a variety of renal diseases for which early treatment is critical.

[Anti-glomerular basement membrane disease: a new disease causing fever of unknown origin?]. / Enfermedad por anticuerpos anti-membrana basal: una nueva enfermedad causante de fiebre de origen desconocido?

Antiglomerular basement membrane disease is an autoimmune disorder characterized by the presence of antibodies directed against glomerular basement membrane. Pyrexia of unknown origin (PUO) is defined as temperatures higher than 38.3 degrees C on several occasions, with a duration of more than 3 weeks, and failure to reach a diagnosis despite 1 week of in-patient investigation. There is a large list of causes of PUO including infections, malignancies and autoimmune diseases, but antiglomerular basement disease has not been described as a cause. We present the first case of antiglomerular basement disease which presented with PUO.

Serum levels of soluble interleukin-2 receptor in patients with ANCA-associated vasculitis.

Serum soluble interleukin-2 receptor (sIL-2R) concentrations were determined using the ELISA method in 19 cases of ANCA-associated vasculitis. These patients were classified as 7 cases of Wegener's granulomatosis (WG) and 12 cases of microscopic polyangiitis (MPA). Elevated levels of sIL-2R were present in the sera of these patients. Levels of serum sIL-2R were not significantly different in patients with WG and MPA either in the active or inactive phase, so the results were expressed as a unified ANCA associated vasculitis group. Concentrations of serum sIL-2R were significantly higher in ANCA-associated vasculitis during the active phase than during the inactive phase (p<0.05), and serum sIL-2R levels were significantly increased in these patients, in the active or inactive stage, compared with a group of healthy subjects (p<0.05). In patients with vasculitis, serum sIL-2R levels correlated with serum levels of C-reactive protein (p<0.05). In the active phase, concentrations of serum sIL-2R correlated to creatinine concentrations. No correlation was found between sIL-2R and ANCA levels in any of the stages of the disease. These findings suggest cellular immune activation in ANCA associated vasculitis.

[Non-convulsive status epilepticus secondary to adjusted cefepime doses in patients with chronic renal failure]. / Estatus epiléptico no convulsivo secundario a cefepima a dosis ajustadas en enfermos con insuficiencia renal crónica.

Fever is one of the most frequent causes of hospital admission in patients with end-stage renal disease. Lack of an identified source of infection and/or lack of clinical response to the first empirical antibiotic treatment favour the use of broader spectrum antibiotics. The availability of fourth-generation cephalosporins (e.g. cefepime) and the increasing incidence of bacterial resistances to classical antibiotics has increased their use in the clinical practice. We present two cases of non-convulsive status epilepticus in patients with advanced chronic renal failure who received cefepime at doses corrected for the degree of renal function according to the manufacturer's instrument as. The clinical symptoms included shouthough, processes, disorientation, loss of attention, and the later appearance of myoclonus. In both cases the electroencephalogram (EEG) was compatible with non-convulsive epileptic status. After cefepime withdrawal there was a clinical remission of symptoms and normalization of the EEG. It is concluded that cefepime treatment can induce a non-convulsive epileptic status in patients with advanced chronic renal failure. Pharmacokinetic studies are urgently needed to clearly define the appropriate dose of cefepime in patients with advanced chronic renal failure.

Relationship between ANCA and disease activity in small vessel vasculitis patients with anti-MPO ANCA.

BACKGROUND: We analysed the usefulness of antineutrophil cytoplasmic antibodies (ANCA) as a marker of clinical activity in patients with small vessel vasculitis associated with anti-myeloperoxidase (MPO) ANCA. METHODS: We studied a group of 25 patients, 15 with microscopic polyangitis and 10 with renal limited vasculitis, so-called rapidly progressive glomerulonephritis type III. The clinical and serological follow-up was accomplished quarterly over an average of 2.79 +/- 2.08 years (range 0.25-6 years). ANCA was analysed by indirect immunofluorescence and enzyme-linked immunosorbent assays (ELISAs). RESULTS: At the time of diagnosis, all patients were ANCA positive (P-ANCA and anti-MPO). Following a standardized treatment, all patients except one achieved complete remission of vasculitis in <3 months. One patient suddenly died during the active phase (1 month of follow-up) and with positive ANCA. Seroconversion from positive to negative occurred in 24/25 patients (96%). Eighteen of these 24 patients (75%) achieved the seroconversion within the first 6 months. During the follow-up, two patients had four major relapses, all of them associated with positive ANCA. ANCA seroconversion from negative to positive was observed in one patient with microscopic polyangitis without clinical relapse of vasculitis. CONCLUSION: ANCA should be used in conjunction with other markers of disease activity in the management of microscopic polyangitis and renal limited vasculitis patients with anti-MPO ANCA.