Early detection of interstitial lung disease in rheumatic diseases: A joint statement from the Portuguese Pulmonology Society, the Portuguese Rheumatology Society, and the Portuguese Radiology and Nuclear Medicine Society.

INTRODUCTION: Interstitial lung disease (ILD) contributes significantly to morbidity and mortality in connective tissue disease (CTD). Early detection and accurate diagnosis are essential for informing treatment decisions and prognosis in this setting. Clear guidance on CTD-ILD screening, however, is lacking. OBJECTIVE: To establish recommendations for CTD-ILD screening based on the current evidence. METHOD: Following an extensive literature research and evaluation of articles selected for their recency and relevance to the characterization, screening, and management of CTD-ILD, an expert panel formed by six pulmonologists from the Portuguese Society of Pulmonology, six rheumatologists from the Portuguese Society of Rheumatology, and six radiologists from the Portuguese Society of Radiology and Nuclear Medicine participated in a multidisciplinary discussion to produce a joint statement on screening recommendations for ILD in CTD. RESULTS: The expert panel achieved consensus on when and how to screen for ILD in patients with systemic sclerosis, rheumatoid arthritis, mixed connective tissue disease, Sjögren syndrome, idiopathic inflammatory myopathies and systemic lupus erythematous. CONCLUSIONS: Despite the lack of data on screening for CTD-ILD, an expert panel of pulmonologists, rheumatologists and radiologists agreed on a series of screening recommendations to support decision-making and enable early diagnosis of ILD to ultimately improve outcomes and prognosis in patients with CTD.

The trabecular bone score: Relationships with trabecular and cortical microarchitecture measured by HR-pQCT and histomorphometry in patients with chronic kidney disease.

The trabecular bone score (TBS) is a novel tool using grayscale variograms of the lumbar spine bone mineral density (BMD) to assess trabecular bone microarchitecture. Studies in patients with chronic kidney disease (CKD) suggest it may be helpful in assessing fracture risk. However, TBS has not been validated as a measure of trabecular architecture against transiliac bone biopsy with histomorphometry in CKD patients. We hypothesized that TBS would reflect trabecular architecture at the iliac crest in CKD patients. We obtained tetracycline double labeled transiliac crest bone biopsy, areal BMD of the spine, total hip, femoral neck (FN) and spine TBS by dual energy X-ray absorptiometry (DXA), and cortical and trabecular volumetric density and microarchitecture by high resolution peripheral quantitative computed tomography (HR-pQCT) in CKD patients from two centers: twenty-two patients from Columbia University Medical Center, USA and thirty patients from Hospital das Clinicas - Universidade de São Paulo, Brazil. Two patients were excluded for outlier status. Univariate and multivariate relationships between TBS and measures from DXA, HR-pQCT and histomorphometry were determined. Patients were 50.2 ±â€¯15.8 years old, 23 (46%) were men, and 33 (66%) were on dialysis. TBS was <1.31 in 21 (42%) patients and 22%, 14% and 10% had T-scores ≤ -2.5 at spine, FN and total hip respectively. In univariate regression, TBS was significantly associated with trabecular bone volume (BV/TV), trabecular width (Tb.Wi), trabecular spacing, cortical width but not with trabecular number or cortical porosity. FN Z-score and height were also associated with cancellous BV/TV and Tb.Wi, In multivariate analysis, TBS remained an independent predictor of BV/TV and Tb.Wi. There were no relationships between TBS and dynamic parameters from histomorphometry. These data suggest that TBS reflected trabecular microarchitecture and cortical width measured by bone biopsy in CKD patients. Future studies should address its utility in the identification of CKD patients who may benefit from fracture prevention strategies.

Biopsy vs. peripheral computed tomography to assess bone disease in CKD patients on dialysis: differences and similarities.

Results from bone biopsy and high-resolution peripheral quantitative computed tomography (HR-pQCT) were compared in 31 CKD patients. There was an agreement mainly for cortical compartment that may represent a perspective on the fracture risk assessment. HR-pQCT also provided some clues on the turnover status, which warrants further studies. INTRODUCTION: Chronic kidney disease (CKD) patients are at high risk of bone disease. Although bone biopsy is considered the best method to evaluate bone disease, it is expensive and not always available. Here we have compared, for the first time, data obtained from bone biopsy and HR-pQCT in a sample of CKD patients on dialysis. METHODS: HR-pQCT and dual-energy X-ray absorptiometry (DXA) were performed in 31 CKD patients (30 on dialysis). Biopsies were analyzed by quantitative histomorphometry, and classified according to TMV. RESULTS: We have found an inverse correlation between radius cortical density measured by HR-pQCT, with serum, as well as histomorphometric bone remodeling markers. Trabecular density and BV/TV measured through HR-pQCT in the distal radius correlated with trabecular and mineralized trabecular bone volume. Trabecular number, separation, and thickness obtained from HR-pQCT and from bone biopsy correlated with each other. Patients with cortical porosity on bone histomorphometry presented lower cortical density at the distal radius. Cortical density at radius was higher while bone alkaline phosphatase was lower in patients with low turnover. Combined, these parameters could identify the turnover status better than individually. CONCLUSIONS: There was an agreement between HR-pQCT and bone biopsy parameters, particularly in cortical compartment, which may point to a new perspective on the fracture risk assessment for CKD patients. Besides classical bone resorption markers, HR-pQCT provided some clues on the turnover status by measurements of cortical density at radius, although the significance of this finding warrants further studies.

Outcomes and Mortality in Renal Transplant Recipients Admitted to the Intensive Care Unit.

INTRODUCTION: In the intensive care unit (ICU), mortality is considered higher among renal transplant recipients than among nontransplantation patients. However, data regarding severe complications after kidney transplantation are scarce. MATERIALS AND METHODS: In this study, we evaluated all consecutive renal transplant recipients admitted to our ICU between July 2012 and July 2013 (n = 70), comparing their outcomes with those of a control group of nontransplantation patients admitted during the same period (n = 153). Among the transplant recipients, we compared survivors and nonsurvivors to identify predictors of ICU mortality. RESULTS: The mean age of the transplant recipients was 52 ± 13 years. Of the 70 transplant recipients, 18 (25%) required mechanical ventilation, 28 (40%) required inotropic support, and 27 (39%) required hemodialysis, all of which are factors that worsen the prognosis significantly. Twenty-two (31%) of the transplant recipients died in the ICU and 17 (24%) died within 30 days after ICU discharge, rates similar to those observed for the control group. CONCLUSIONS: We observed similar mortality between recipient and control groups, albeit the mortality was higher in the clinical group. In the multivariate model, the need for mechanical ventilation and the need for hemodialysis were independently associated with mortality.

Pneumocystis jirovecii pneumonia with an atypical granulomatous response after kidney transplantation.

Pneumocystis jirovecii pneumonia (PCP) continues to be a leading cause of morbidity and mortality in kidney transplant recipients. Granulomatous PCP is an unusual histological presentation that has been described in a variety of immunosuppressive conditions. Previous studies have demonstrated an association between granulomatous disorders and hypercalcemia, the purported mechanism of which is extrarenal production of 1,25-dihydroxyvitamin D by activated macrophages. Here, we report a case of granulomatous formation in a kidney transplant recipient with PCP who presented with hypercalcemia and suppressed parathyroid hormone, both of which resolved after successful treatment of the pneumonia. In immunocompromised patients, pulmonary infection associated with hypercalcemia should raise the suspicion of PCP and other granulomatous disorders.

De novo thrombotic microangiopathy after kidney transplantation: clinical features, treatment, and long-term patient and graft survival.

INTRODUCTION: Posttransplant thrombotic microangiopathy (TMA)/hemolytic uremic syndrome (HUS) can occur as a recurrent or de novo disease. METHODS: A retrospective single-center observational study was applied in order to examine the incidence and outcomes of de novo TMA/HUS among transplantations performed between 2000 and 2010. Recurrent HUS or antibody-mediated rejections were excluded. RESULTS: Seventeen (1.1%) among 1549 kidney transplant recipients fulfilled criteria for de novo TMA. The mean follow-up was 572 days (range, 69-1769). Maintenance immunosuppression was prednisone, tacrolimus (TAC), and mycophenolic acid in 14 (82%) patients. Mean age at onset was 40 ± 15 years, and serum creatinine was 6.1 ± 4.1 mg/dL. TMA occurred at a median of 25 days (range, 1-1755) after transplantation. Nine (53%) patients developed TMA within 1 month of transplantation and only 12% after 1 year. Clinical features were anemia (hemoglobin < 10 g/dL) in 9 (53%) patients, thrombocytopenia in 7 (41%), and increased lactate dehydrogenase in 12 (70%). Decreased haptoglobin was observed in 64% and schistocytes in 35%. Calcineurin inhibitor (CNI) withdrawal or reduction was the first step in the management of 10/15 (66%) patients, and 6 (35%) received fresh frozen plasma (FFP) and/or plasmapheresis. TAC was successfully reintroduced in six patients after a median of 17 days. Eight (47%) patients needed dialytic support after TMA diagnosis and 75% remained on dialysis. At 4 years of follow-up, death-censored graft survival was worse for TMA group (43.0% versus 85.6%, log-rank = 0.001; hazard ratio = 3.74) and there was no difference in patient survival (53.1% versus 82.2%, log-rank = 0.24). CONCLUSION: De novo TMA after kidney transplantation is a rare but severe condition with poor graft outcomes. This syndrome may not be fully manifested, and clinical suspicion is essential for early diagnosis and treatment, based mainly in CNI withdrawal and FFP infusions and/or plasmapheresis.

Lupus nephritis is more severe in children and adolescents than in older adults.

OBJECTIVE: To evaluate clinicopathological features and treatment response in patients with lupus nephritis (LN), comparing the childhood- and late-onset forms of the disease. METHODS: We retrospectively analyzed clinical presentation, treatment and evolution in patients diagnosed with LN by renal biopsy between 1999 and 2008. Patients were grouped by age-≤18 years (n = 23); and ≥50 years (n = 13)-and were followed for the first year of treatment. RESULTS: The baseline features of the childhood- and late-onset groups, respectively, were as follows: mean age, 15 ± 2 and 54 ± 5 years; female gender, 87% and 92%; hypertension, 87% and 77%; Systemic Lupus Erythematosus Disease Activity Index, 29 ± 9 and 17 ± 7 (p = 0.002); estimated glomerular filtration rate (eGFR), 86 ± 66 and 70 ± 18 ml/min; concurrent SLE/LN diagnosis, 90% and 15% (p < 0.001); crescents on biopsy, 74% and 30% (p = 0.02); activity index on biopsy, 4.8 ± 2.6 and 3.3 ± 1.9 (p = 0.10); and interstitial fibrosis (>10%), 39% and 61% (p = 0.08). Treatment consisted mainly of methylprednisolone, prednisone and intravenous cyclophosphamide, average cumulative doses being similar between the groups. After 12 months of treatment, the eGFR in the younger and older patients was 116 ± 62 and 78 ± 20 ml/min, respectively (p = 0.005). Three of the younger patients progressed to dialysis at 12 months, compared with none of the older patients. CONCLUSION: Childhood-onset LN seems to be more severe than is late-onset LN.