Mucin-1 Gene Mutation and the Kidney: The Link between Autosomal Dominant Tubulointerstitial Kidney Disease and Focal and Segmental Glomerulosclerosis.

Glomerular diseases are one of the most frequent causes of chronic kidney disease, focal and segmental glomerulosclerosis being one of the commonest glomerulopathies. However, the etiology of this glomerular entity, which merely depicts a morphologic pattern of disease, is often not established and, in most of the patients, remains unknown. Nephrologists tend to assume focal and segmental glomerulosclerosis as a definitive diagnosis. However, despite the increasing knowledge developed in the field, genetic causes of glomerular diseases are currently identified in fewer than 10% of chronic kidney disease subjects. Moreover, unexplained familial clustering among dialysis patients suggests that genetic causes may be underrecognized. Secondary focal and segmental glomerulosclerosis due to genetic mutations mainly located in the podocyte and slit diaphragm can occur from childbirth to adulthood with different clinical presentations, ranging from mild proteinuria and normal renal function to nephrotic syndrome and renal failure. However, this histopathological pattern can also be due to primary defects outside the glomerulus. The present report illustrates an adult case of secondary focal and segmental glomerulosclerosis with a dominant tubulointerstitial damage that led to the pursue of its cause at the tubular level. In this patient with an undiagnosed family history of adult kidney disease, a genetic study unraveled a mutation in the mucin-1 gene and a final diagnosis of adult dominant tubular kidney disease-MUC1 was made.

In Acute IgA Nephropathy, Proteinuria and Creatinine Are in the Spot, but Podocyturia Operates in Silence: Any Place for Amiloride?

IgA nephropathy is the most frequent cause of primary glomerulonephritis, portends erratic patterns of clinical presentation, and lacks specific treatment. In general, it slowly progresses to end-stage renal disease. The clinical course and the response to therapy are usually assessed with proteinuria and serum creatinine. Validated biomarkers have not been identified yet. In this report, we present a case of acute renal injury with proteinuria and microscopic hematuria in a young male. A kidney biopsy disclosed IgA nephropathy. Podocyturia was significantly elevated compared to normal subjects. Proteinuria, renal function, and podocyturia improved promptly after steroids and these variables remained normal after one year of follow-up, when steroids had already been discontinued and patient continued on valsartan and amiloride. Our report demonstrates that podocyturia is critically elevated during an acute episode of IgA nephropathy, and its occurrence may explain the grim long-term prognosis of this entity. Whether podocyturia could be employed in IgA nephropathy as a trustable biomarker for treatment assessment or even for early diagnosis of IgA nephropathy relapses should be further investigated.

Initially Nondiagnosed Fabry's Disease when Electron Microscopy Is Lacking: The Continuing Story of Focal and Segmental Glomerulosclerosis.

Focal and segmental glomerulosclerosis is classified as either primary or secondary. We present a patient with a past history of biopsy-proven focal and segmental glomerulosclerosis. Despite initial response to dual blockade and steroids, proteinuria raised when steroids were decreased. After the patient was restarted on steroids, proteinuria did not improve. Another biopsy confirmed the previous diagnosis but suggested Fabry's disease, later confirmed by electron microscopy, α-galactosidase A serum and leukocyte deficiency as well as genetic studies. Proteinuria decreased when agalsidase ß was prescribed in parallel with steroid tapering, increased with steroid discontinuation and improved with meprednisone administration. This report highlights the relevance of electron microscopy in kidney biopsy. In glomerulosclerosis, despite specific treatment, secondary hemodynamic and immunologic pathways may contribute to the development of proteinuria and accelerate the renal disease progression due to the primary disease. We discuss possible pathophysiologic pathways involved in proteinuria in Fabry's disease according to the biopsy and the therapeutic response.

Carcinoma broncoalveolar: sobrevida a cinco años / Bronchioalveolar carcinoma: five year survival

The epidemiology and prognosis of bronchioalveolar carcinoma (BAC) is different from adenocarcinoma. We studied 28 patients who underwent surgical resection and in whom a final histologic diagnosis of bronchioalveolar carcinoma was made. Sixty one percent of patients were asymptomatic at the time of diagnosis. The most usual radiological presentations were pulmonary nodule (11), pulmonary mass (6) and diffuse infiltrate (6). Nine patients (9/25) were never smokers. Bronchoscopy provided the diagnosis only in 4/26 patients. Patients were classified as stage IA 11/24, IB 5/24 IIIB in 2/24 and IV in 6/24. Five-year survival for the entire group was 65%. Patients with focal lesions had a longer survival. The survival in patients who underwent potentially curative resections was 62.8 +/- 44.0 months. When surgery was considered non-curative, survival was 21.2 +/- 19.5 months (p = 0.0064). Five-year survival in stage IA patients was 80%. Survival of patients with non-mucinous histology was longer than those with mucinous type carcinomas (54.9 +/- 25.0 months vs. 5.33 +/- 4.04, p < 0.0001) but the 5-year-survival was not statistically different. In conclusion, BAC has a favourable prognosis. The best survival rate was found in focal forms, represented by early tumor, nodes, metastasis (TNM) stages and non-mucinous BAC among the histological groups.

Lipoblastoma-lipoblastomatosis associated with unilateral limb hypertrophy: a case report in a newborn.

Lipoblastoma is a benign mesenchymal tumor of embryonic adipose tissue, uncommon in infancy. Multicentricity, absence of a capsule and histopathology best defines a lipoblastoma. Synonyms for this lesion are embryonic lipoma, fetal lipoma, lipoblastic tumor, and congenital lipomatoid tumor. Lipoblastoma is more common in males (approximately 80%), is usually located in the subcutaneous soft tissue (benign lipoblastoma) or in the deep interstitium (benign lipoblastomatosis), or sometimes in all corporeal segments. Primary treatment is complete excision. Relapse is between 14-25%, many of which are more "mature," and difficult to differentiate from lipoma. The differential diagnosis includes liposarcoma, which is rare under ten years. Radical excision in children is recommended with relapses, especially with lipoblastomatosis. Chromosomal markers help discriminate between liposarcoma and lipoblastoma.

Late-onset cytomegalovirus-associated interstitial nephritis in a kidney transplant.

Cytomegalovirus is the most important viral infection in kidney transplants, but rarely affects the allograft after the sixth month posttransplantation. We present a patient who developed renal failure eighteen months posttransplant; a kidney biopsy showed cytomegalovirus inclusions, acute tubular necrosis and mild interstitial nephritis. After intravenous ganciclovir, renal function transiently improved. Cytomegalovirus pp65 antigen was weekly reported as negative. One month later another biopsy was performed due to renal failure. The findings were consistent with tubular atrophy and severe interstitial nephritis. No cytomegalovirus cellular inclusions were found on histology, including immunohistochemical and polymerase chain reaction studies; pp65 antigen studies were persistently negative. Despite an attempt to recover renal function with steroid therapy, the patient restarted hemodialysis 20 months posttransplantation. This report suggests that cytomegalovirus should be considered as a late cause of kidney failure even in the absence of infection-related symptoms. The irreversible allograft damage can be caused despite the successful eradication of the virus with intravenous ganciclovir.

Immunoglobulin A nephropathy and ulcerative colitis. A focus on their pathogenesis.

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.

[Follicular dendritic cell sarcoma in a lymph node]. / Sarcoma de celulas foliculares dendriticas en ganglio linfatico.

We report the case of a 39 years old man who presented with a rapidly enlarging, painless mass in his left side of the neck. The mass was excised and turned out to be a lymph node. Histologically, it showed a proliferation of oval to spindle cells growing in sheets and fascicles, occasionally forming a storiform pattern. Tumor cells showed large nuclei, dispersed chromatin and small evident nucleoli. Neoplastic cells were positive for immunohistochemical markers vimentin, CD 68, CD 21, CD 35 and R 4/23. Ultrastructural examination showed long cytoplasmatic processes joined by desmosomes. The patient was treated with local radiotherapy and is alive and well 18 months after the excision. Follicular dendritic cell sarcoma is a very unusual tumor that merits wider recognition.

[Liver histology in chronic hemodialysis patients infected with hepatitis C virus]. / Histología hepática en pacientes hemodializados crónicos infectados con el virus de la hepatitis C.

Liver biopsies were analyzed in 21 patients with chronic renal failure (CRF) who tested positive for Hepatitis C Virus (HCV), using Elisa II and/ or PCR. The study included 14 men and 7 women, the average age being 41 years old (range: 20-65). The average span of time under dialysis was 64 months (range: 12-192). Hbs ag. was positive in six patients. Patients underwent biopsy for showing persistent rise of transaminase for more than 6 months. The modified Knodell Index was used to grade hepatic lesions. All biopsies showed chronic hepatitis, of which 2 were associated with cirrhosis. Eight patients were infected with mild chronic hepatitis, ten were infected with moderate chronic hepatitis, and only three patients had a severe lesion. Fibrosis was mild in 13 cases, moderate in 6, and 2 had cirrhosis. Chronic Hepatitis C characteristic lesions analysis showed lymphoid nodules in 6 cases (29%), ductal epithelium lesions in 7 (33%), and steatosis in 7 (33%). Chronic HCV infection in our patients seems to have histologic characteristics similar to those reported in HCV positive non CRF patients.