Alejandro Iotti

Immunoglobulin A Nephropathy and Ulcerative Colitis

The immune response has largely been implicated in the pathogenesis of inflammatory bowel disease (ulcerative colitis and Crohn’s disease) and immunoglobulin A nephropathy. We present a 26-year-old woman with a long past history of asymptomatic macroscopic hematuria who later developed several episodes of bloody stools and abdominal pain. A colonic biopsy disclosed ulcerative colitis and a renal biopsy was consistent with immunoglobulin A nephropathy. Immunoglobulin A nephropathy is the most common glomerulonephritis, being end-stage renal disease a rare but the most serious complication. It can be primary or secondary, but the association between both entities is unusually observed. We discuss the possible immunologic mechanisms involved and believe the initial immunologic derangement originates in the bone marrow. We suggest both conditions must be considered when either a patient with ulcerative colitis and micro- or macrohematuria or with renal involvement and a past history of diarrhea or abdominal pain presents.

Analysis of Survival in 400 Surgically Resected Non-small Cell Lung Carcinomas: Towards a Redefinition of the T Factor

Introduction: The tumor, node, metastasis (TNM) system has been recognized internationally as the standard for staging disease extension, but despite the improvements of the 1997/2002 international staging system, there may be marked differences in postoperative 5-year survival rates within each stage. There is controversy about the impact of tumor size itself as a variable unrelated to stage. The objective of this study was to analyze the influence of tumor size on the survival in patients with surgically resected non-small cell lung carcinoma (NSCLC). Methods: Between August 1985 and January 2006, 400 patients underwent pulmonary resection with a curative intention for non-small cell lung carcinoma. Patients were excluded if they had received neoadjuvant chemotherapy. The clinicopathological records of each patient were examined for prognostic factors such as age, sex, right or left side cancer, histology, tumor location, tumor size, clinical nodal stage number, and distribution of metastatic nodes. Results: Operative mortality was 2.2% for lobectomy and 18% for pneumonectomy (p < 0.05). Adenocarcinoma was the most common type (n = 245, 61.2%). Surgery was considered a complete resection in 341 patients (85.2%). When only patients without neoplastic hilar or mediastinal metastases (pN0) were included, the difference in survival was significantly different in terms of tumor size (log rank 28.46, p < 0.0001). Univariate analysis for the group of pN0 patients showed survival was not significantly affected by age, sex, side, or adenocarcinoma histology. In the multivariate analysis, tumor size and the T factor were found to have maintained its independent prognostic effects on overall survival. Among patients with pN0 tumors smaller that 15 mm in diameter, 5-year survival was 95% whereas patients with tumors bigger than 16 mm in diameter had a 5-year survival of 65% (p < 0.0001). Conclusion: In conclusion, our data suggest that tumors over 15 mm are associated with shorter 5-year survival in all TNM stages. Current TNM categories are not sufficiently discriminatory and the T factor requires to be reevaluated in further revisions of the TNM classification.

Belatacept and mediastinal histoplasmosis in a kidney transplant patient.

Background: In transplantation immunosuppression enhances the appearance of opportunist infections. An ideal balance between the prevention of rejection, the lowest risk of infections and the highest rates of graft survival is a continuous challenge. Lower doses of immunosuppression may diminish the risk of infections, metabolic and hemodynamic complications or even of malignancy, but may expose patients to episodes of acute rejection. New drugs are being developed to improve graft survival at the lowest risk of side effects. Belatacept has recently been introduced in kidney transplantation to inhibit the co-ligand signal of T cell stimulation. It is a drug with a safe profile, is well-tolerated and appears to improve long-term survival of kidney grafts. However, there may be an increase in opportunistic infections which may be facilitated by T cell depression, as Aspergillus sp., Cryptococcus neoformans or tuberculosis. Case Presentation: We describe a 59-year-old female who developed fever, clinical wasting and a mediastinal mass 31 months after receiving a living non-related kidney transplant while on belatacept therapy. A mediastinal node biopsy disclosed the presence of Histoplasma capsulatum. Infection successfully resolved after appropriate antifungal treatment. Conclusions: To our knowledge, this is the first reported case of Histoplasma capsulatum in a kidney transplanted patient on belatacept therapy

In IgA Nephropathy, Glomerulosclerosis Is Associated with Increased Urinary CD80 Excretion and Urokinase-Type Plasminogen Activator Receptor-Positive Podocyturia

Background: Podocyturia may determine the evolution to podocytopenia, glomerulosclerosis, and renal failure. According to the Oxford classification of IgA nephropathy (IgAN), the S1 lesion describes glomerulosclerosis. Urokinase-type plasminogen activator receptor (uPAR) participates in podocyte attachment, while CD80 increases in glomerulosclerosis. We measured uPAR-positive urinary podocytes and urinary CD80 (uCD80) in controls and in IgAN subjects with M1E0S0T0 and M1E0S1T0 Oxford scores to assess a potential association between podocyturia, inflammation, and glomerulosclerosis. Methods: The groups were as follows: controls (G1), n = 20 and IgAN group (G2), n = 39, subdivided into M1E0S0T0 (G2A), n = 21 and M1E0S1T0 (G2B), n = 18. Among the included variables, we determined uPAR-positive podocytes/gram of urinary creatinine (gUrCr) and uCD80 ng/gUrCr. Biopsies with interstitial fibrosis and tubular atrophy <10% were included. Results: Groups were not different in age and gender; urinary protein-creatinine (uP/C) ratio, Chronic Kidney Disease-Epidemiology Collaboration (CKD-EPI) equation, uPAR-positive podocytes/gUrCr, and uCD80 were significantly increased in G2 versus G1. G2A and G2B were not different in age, gender, hypertension, and follow-up. G2B displayed significantly higher uP/C, uPAR-positive podocytes, uCD80, and lower CKD-EPI versus G2A. Strong significant correlations were encountered between uCD80 and podocyturia in G2A and G2B. However, when G1 was compared to G2A and G2B separately, the differences with respect to uP/C, uPAR-positive podocytes, and podocyturia were significantly stronger versus G2B than versus G2A. Conclusions: IgAN presents elevated uCD80 excretion and uPAR-positive podocyturia, while CD80 correlates with podocyturia. Glomerulosclerosis (S1) at the time of biopsy is associated with higher uP/C, lower renal function, increased uPAR-positive podocyturia, and CD80 excretion, and is independent of M1. In IgAN, uPAR may participate in podocyte detachment.

Enfermedad renal por depósito idiopático de cadenas livianas: Caso clínico

Idiopathic Light Chain disease (ILCD) is a systemic disease characterized by a deposit in different organs of light chain monoclonal immunoglobulins, produced by an abnormal clone ofB cells. It is usually found in the course ofa plasma cell dyscrasia and in other lymphoproliferative alterations; however it may occur in absence of any hematologic disease and is denominated as idiopathic. We report a 51-year-old mole admitted to the hospital due to anasarca. Laboratory evaluation showed a serum creatinine of 1.4 mg/dl, a serum albumin of1.6 g/dl, a serum cholesterol of 687 mg/dl and a proteinuria of 5.3 g/day Light chains with a predominance of a monoclonal component were identified in urinary proteins by electrophoresis and kappa chains were identified by immunofixation. A renal biopsy showed a diffuse nodular glomerulopathy with a 35% tubular atrophy and interstitial sclerosis. Electron microscopy confirmed light chain deposition. The bone marrow biopsy showed a myeloid hyperplasia. Thepatient was initially treated with methylprednisolone and plasmapheresis with a reduction in serum creatinine and disappearance of urinary kappa component. Albuminuriapersisted and a malnutrition-inflammatory complex syndrome was diagnosed. Hemodialysis with ultrafiltration was started along with cyclophosphamide. Thepatient receivedhemodialysisforsixmonths and continued with methylprednisolone.Idiopathic Light Chain disease (ILCD) is a systemic disease characterized by a deposit in different organs of light chain monoclonal immunoglobulins, produced by an abnormal clone of B cells. It is usually found in the course ofa plasma cell dyscrasia and in other lymphoproliferative alterations; however it may occur in absence of any hematologic disease and is denominated as idiopathic. We report a 51-year-old mole admitted to the hospital due to anasarca. Laboratory evaluation showed a serum creatinine of 1.4 mg/dl, a serum albumin of1.6 g/dl, a serum cholesterol of 687 mg/dl and a proteinuria of 5.3 g/day Light chains with a predominance of a monoclonal component were identified in urinary proteins by electrophoresis and kappa chains were identified by immunofixation. A renal biopsy showed a diffuse nodular glomerulopathy with a 35% tubular atrophy and interstitial sclerosis. Electrón microscopy confirmed light chain deposition. The bone marrow biopsy showed a myeloid hyperplasia. The patient was initially treated with methylprednisolone and plasmapheresis with a reduction in serum creatinine and disappearance of urinary kappa component. Albuminuria persisted and a malnutrition-inflammatory complex syndrome was diagnosed. Hemodialysis with ultrafiltration was started along with cyclophosphamide. The patient received hemodialysis for six months and continued with methylprednisolone.