Pivotal role of paricalcitol in the treatment of calcific uremic arteriolopathy in the presence of a parathyroid adenoma.

Calcific uremic arteriolopathy, or calciphylaxis, is a serious and life-threatening complication of end-stage renal disease. Its pathogenesis is not yet fully elucidated and treatment is controversial. In the presence of severe hyperparathyroidism, parathyroidectomy should be considered. We report a case of a woman on maintenance hemodialysis therapy with calciphylaxis and parathyroid adenoma who refused to undergo parathyroidectomy. She was treated successfully with a combination of noncalcium phosphate binders, cinacalcet, and paricalcitol. Subcutaneous plaques disappeared, and the necrotic lesion was healed. Discontinuation of paricalcitol led to an increase in serum parathyroid hormone levels and reappearance of the patient's symptoms, whereas its reintroduction resulted in complete remission of the clinical picture. Paricalcitol, a less calcemic vitamin D analogue, is also a selective vitamin D receptor activator with a number of nonclassic actions (such as inhibition of inflammation and ossification-calcification) that could prove beneficial in cases of calciphylaxis.

Mediastinal gastroenteric cyst in a neonate containing respiratory-type epithelium and pancreatic tissue.

Mediastinal gastroenteric cyst is an uncommon congenital malformation and a distinct histopathological entity within the family of foregut duplication cysts. This lesion is mainly encountered in neonates and infants. Histologically, it is characterized by double-layered smooth muscle wall and gastric lining mucosa. We report on a case of a 2-day-old girl, with a posterior mediastinal cystic mass associated with T3-T4 hemivertebrae, presenting with severe respiratory distress. The cyst was multilocular, surgically removed, and histopathologic analysis revealed that it was of gastroenteric type. However, in numerous areas of the lesion, respiratory-type epithelium was observed, as well as pancreatic tissue. After removal of the lesion the patient made an uneventful recovery and shows no signs of long-term pulmonary sequelae. We failed to demonstrate in the available literature the presence of this variable epithelial lining within a single mediastinal foregut cyst. In addition, pancreatic tissue within an intrathoracic enteric cyst has been reported only twice.

Urinary levels of epidermal growth factor, interleukin-6 and monocyte chemoattractant protein-1 may act as predictor markers of renal function outcome in immunoglobulin A nephropathy.

AIM: Urinary cytokine excretion may reflect histological changes in immunoglobulin A nephropathy (IgAN), and their measurement can give information about disease outcome. METHODS: Thirty-three IgAN patients were prospectively followed for 5.6 +/- 3.1 years. Urinary levels of monocyte chemoattractant protein-1 (MCP-1), interleukin (IL)-6 and epidermal growth factor (EGF) were measured at diagnosis and repeated 1 year later for IL-6 and EGF. RESULTS: Urinary MCP-1 and IL-6 levels were increased significantly, while EGF excretion reduced in IgAN patients, compared to controls. IL-6 urinary levels showed significant positive correlation with chronic histological lesions. Patients were classified into five groups, according to the Haas classification system. MCP-1 and IL-6 urinary levels were increased, whereas EGF levels were reduced in the progression of staging. EGF urinary excretion was a strong predictor factor of disease outcome, significantly correlated with creatinine clearance at time of diagnosis (r = 0.5, P = 0.005), and at the end of follow up (r = 0.6, P = 0.001). Urinary EGF levels measured a year later could predict long-term outcome better, and a cut of 0.05 pg/mg urine creatinine levels could distinguish between progressors and non-progressors. CONCLUSION: Urinary MCP-1, IL-6 and EGF levels may represent histology in IgAN. EGF excretion can be a predictive marker and its serial measurements may give information about disease outcome and the effect of treatment.

Unusual manifestation of diarrhea-associated haemolytic uraemic syndrome in an adult.

Hemolytic-Uremic Syndrome (HUS) is an uncommon disease characterized by microangiopathic hemolytica anaemia, thrombocytopenia, and acute renal failure. There are two forms of HUS: diarrhoea (D+)- and non-diarrhoea (D-)-associated HUS. We report the case of a 21-year-old woman presented to our department with jaundice, anaemia, thrombocytopenia, and anuria, preceded by a diarrheal prodrome, secondary to infection with Escherichia coli O157:H7. The whole clinical and laboratory investigation led to the diagnosis of HUS. Her condition was complicated with cholestasis, liver dysfunction, bleeding from the vagina, and myocardial involvement. She was treated only with fresh frozen plasma transfusions and hemodialysis, and despite the long duration of anuria (22 days), the patient showed subsequent improvement over days until full recovery one month later.

Serum thyrotropin concentration as a biochemical predictor of thyroid malignancy in patients presenting with thyroid nodules.

PURPOSE: Serum thyrotropin (TSH) is a well-established growth factor for thyroid nodules and suppression of TSH concentrations by administering exogenous thyroxine may interfere with the growth of established nodules as well as the formation of new thyroid nodules. The aim of this study was to investigate whether serum TSH at presentation is a predictor of thyroid malignancy in patients with thyroid nodules. METHODS: A total of 565 patients without overt thyroid dysfunction, who presented with palpable thyroid nodule(s) between 1988 and 2004 and underwent at least one fine-needle aspiration biopsy, were retrospectively evaluated. RESULTS: The final diagnostic outcome was established after surgery (n = 122) or after a minimum of 1-year clinical follow-up period. Higher rates of malignancy were observed in patients with serum TSH in the upper tertile of the normal range (P = 0.026). Binary logistic regression analysis revealed significantly increased adjusted odds ratios for the diagnosis of malignancy in patients with serum TSH 1.5-4.0 mIU/l when compared to those with either TSH 0.4-0.8 mIU/l (P = 0.005) or TSH 0.9-1.4 mIU/l (P = 0.007). CONCLUSIONS: The risk of malignancy in thyroid nodules increases in parallel with TSH concentrations within the normal range. TSH concentration at presentation is an independent predictor of thyroid malignancy.

Fibrotic mechanisms in idiopathic rapidly progressive glomerulonephritis: the role of TGF-beta1 and C5b-9.

BACKGROUND: Idiopathic IRPGN is a form of renal vasculitis in which a high chronicity index is present despite minimal impairment of renal function. The present study investigated the mechanisms underlining the relatively early appearance of fibrosis. METHODS: In all, 34 patients (17 males) with biopsy proven idiopathic RPGN were included. On light microscopy, the percentage and evolution stage of crescents, the presence of glomerular necrosis, the degree or severity of arteriosclerosis, as well as the extent of tubulointerstitial (TIN) infiltration, interstial fibrosis, and tubular atrophy were assessed. Monoclonal antibodies were used to identify infiltrating macrophages, HLA-DR (+), alpha-SMA (+), and PCNA (+) cells, the expression of the adhesion molecule ICAM-1, the growth factor TGF-beta1, and the terminal complement component C5b-9. RESULTS: The presence of glomerular necrosis correlated positively with the number of SMA (+) cells in TIN (p = 0.036). Glomerular TGF-beta1 expression had positive correlation with tubular C5b-9 expression. The tubulointerstitial TGF-beta1 expression correlated with tubular C5b-9 expression (p = 0.001) and TGF-beta1 expression (p = 0.009). Independent factors predicting the severity of renal function impairment were the CRP levels (p = 0.002) and the degree of arteriosclerosis (p = 0.01). CRP levels correlated with the severity of interstitial infiltration and fibrosis (p = 0.02), the expression of TGF-beta1 in the glomeruli (p = 0.009) and the interstitial space (p = 0.001), and the intensity of tubular ICAM-1 and C5b-9 expression (p = 0.023, p = 0.002, respectively). The severity of proteinuria showed a significant correlation with the expression of TGF-beta1 in the glomeruli (p = 0.033) and the tubulointerstitium (p = 0.019). CONCLUSIONS: The activation of interstitial fibroblasts seems to be an early phenomenon that is related to the extent of glomerular necrosis. Glomerular TGF-beta1 may induce tubular expression of C5b-9. Increased tubular C5b-9 expression may result in interstitial fibrosis through increased TGF-beta1 production.

Necrotic vasculitis in a patient with abdominal fibromatosis and Guillain-Barré syndrome.

The case of a 65-year-old woman presenting with Guillain-Barré syndrome is herein reported. Tomographic investigation revealed abdominal and retroperitoneal fibromatosis. During her hospitalization, renal involvement ensued, and subsequent renal biopsy demonstrated findings of crescentic pauci-immune glomerulonephritis negative for ANCA antibodies and with characteristics indicative of necrotic angiitis. The simultaneous existence of the three diseases in the same patient as well as the relation between necrotic vasculitis and G-B syndrome is speculated, and the relevant literature is reviewed.

Predictors of outcome in idiopathic rapidly progressive glomerulonephritis (IRPGN).

BACKGROUND: Small vessel vasculitides are known to follow a devastating course towards end-stage renal disease, unless treated with immunosuppressive regiments. We investigated the value of clinical, histological and immunohistochemical parameters as predictors of outcome at diagnosis in patients with pauci immune necrotizing glomerulonephritis. METHODS: In 34 patients the percentage and evolution stage of crescents, the presence of glomerular necrosis, the degree or severity of arteriosclerosis, as well as the extent of tubulointerstitial infiltration, interstial fibrosis and tubular atrophy were assessed. Monoclonal antibodies were used to identify infiltrating macrophages, alpha-SMA(+) and PCNA(+) cells, the expression of integrins alpha3beta1 and LFA-1beta, the adhesion molecule ICAM-1, the growth factor TGF-beta1 and the terminal complement component C5b-9. RESULTS: 24 pts (70.6%) showed a complete or partial response to the treatment. The follow-up period was 20 +/- 22 months. At multivariate analysis, serum CRP (p = 0.024), the intensity of tubular expression of C5b-9 (p < 0.0001) as well as the extent of glomerular and tubular expression of alpha3beta1 integrin (p = 0.001 and 0.008 respectively) independently predicted the response to treatment. The response rate was better in ANCA(+) pts (p = 0.008). The extent of interstitial infiltrate (p < 0.0001), the severity of tubulointerstitial fibrosis (p < 0.0001) and the severity of tubular TGF-beta1 expression (p < 0.0001) were independent predictors of long term outcome of renal function. CONCLUSION: Patients with ANCA-associated renal vasculitis seem to respond better to the treatment. Acute phase reactants, such as CRP, implying a more intense parenchymal inflammatory reaction, as well as the intensity of the de novo expression of C5b-9 and the glomerular and tubular expression of alpha3beta1 integrin predict the response to therapy. The severity of TIN lesions and of the tubulo-interstitial TGF-beta1 and C5b-9 expression predict an unfavourable outcome.

Renal cancer in a patient with Crohn's disease and secondary amyloidosis.

Herein we report the case of a patient suffering from renal amyloidosis secondary to Crohn's disease (CD) who presented with anuria and anasarca 8 years after commencement of colchicine treatment. End-stage renal disease was confirmed. Renal imaging prior to hemodialysis showed tumor of the left kidney. Histopathology after nephrectomy revealed secondary amyloidosis as well as the existence of cancer (hypernephroma). We discuss the presence of renal amyloidosis secondary to CD and at the same time renal cancer development, a combination that has not been reported so far, and we emphasize the surprisingly long renal survival of this patient after colchicine treatment.

Induction and long-term treatment with cyclosporine in membranous nephropathy with the nephrotic syndrome.

BACKGROUND: Cyclosporine A (CyA) has been shown to be effective in membranous nephropathy (MN). However, the optimal dose and the duration of treatment remain controversial issues. We evaluated the efficacy of low-dose CyA alone or combined with corticosteroids as induction and long-term treatment for nephrotic patients with MN. METHODS: In the first part of the study, 51 nephrotic patients with MN were treated either with CyA and prednisolone (n=31) or CyA alone (n=20) for 12 months. Patients who responded with complete remission (CR) or partial remission (PR) were placed on long-term treatment with lower doses of CyA and prednisolone or CyA alone. The mean follow-up of the second part of the study was 26+/-16 months and 18+/-7 months, respectively. RESULTS: After 12 months of treatment, 26 patients in the combination group and 17 patients in the monotherapy group had a CR or PR of proteinuria (P=NS). Renal function was unchanged in the two groups. During long-term treatment relapses were more frequent in the monotherapy group (47 vs 15%, P<0.05). Daily CyA dose was higher in non-relapsers in both groups (combination 1.4+/-0.5 vs 1.0+/-0.3 mg/kg, P<0.001, monotherapy 1.5+/-0.4 vs 1.1+/-0.2 mg/kg, P<0.003). Relapsers in both groups had lower CyA trough levels (72+/-48 ng/ml) compared with non-relapsers (194+/-80 ng/ml) (P<0.03). Renal function and proteinuria remained stable during the follow-up. CONCLUSION: This study suggests that 12-month therapy with CyA (+/-prednisolone) is effective in inducing remission in most nephrotic patients with MN and well-preserved renal function. Longer treatment with lower doses is a useful approach to maintain remission. Relapses occur more frequently in the monotherapy group and usually are associated with CyA trough levels<100 ng/ml.

Antibiotics-induced acute interstitial nephritis in 6 children.

INTRODUCTION: Antibiotics-induced acute interstitial nephritis (AIN) is a rare disorder in children, and the diagnosis is often delayed. However, many commonly prescribed antibiotics seem to be implicated. PATIENTS AND METHODS: We reviewed the medical records of 6 children, age range from 10 months to 14 years, with biopsy-confirmed antibiotics-induced AIN. Clinical presentation, morphological findings, and outcomes are reported. RESULTS: Symptoms of AIN started 2-4 weeks after antimicrobial therapy with beta-lactam antibiotics in 5 children and with gentamicin in 1 child. All patients presented with acute renal failure and fever. The glomerular filtration rate was dramatically reduced in 2 cases and mildly reduced in 4 patients. Two of our patients had supportive treatment, 2 received corticosteroid therapy, and 2 children remained under peritoneal dialysis for 12 and 22 days, respectively. Five patients had a full recovery of their renal function, and 1 child, 2 years later, still presented impairment of the renal function. CONCLUSION: AIN should be considered in case of acute renal failure in children, mostly when other common causes have been excluded, and there is a history of drug exposure.

Colchicine treatment of liver fibrosis.

BACKGROUND/AIMS: Because of its antifibrotic and anti-inflammatory effects, colchicine has been proposed as a treatment for liver disease. The results from clinical trials have however been inconsistent. The aim of the present study was to evaluate the effect of colchicine in the treatment of patients with hepatic fibrosis of various etiologies. METHODOLOGY: Thirty-eight patients were randomized to receive either colchicine 1 mg per day (n=21, group A) or no antifibrotic agent (n=17, group B). Treatment lasted for at least 12 months. Liver biopsy was performed prior to entry and after 12 months. Liver function tests, serum aminoterminal peptide of procollagen III (PIIINP) levels and CD4:CD8 ratio of peripheral blood T lymphocytes (PBTLs) were performed at baseline and bimonthly or every 4 months post-treatment. RESULTS: Mean albumin serum levels increased 12 months post-treatment period only in group A (p<0.05). Mean serum PIIINP levels did not change significantly after 12 months of treatment in group A; in 7 patients a reduction in mean serum PIIINP levels was noticed during 24-month post-treatment follow-up period (p<0.05). At baseline, a correlation between focal or bridging necrosis and CD4:CD8 ratio of PBTLs was noticed in group A (p < 0.05). The mean serum CD4:CD8 ratio was increased after 12 months of colchicine treatment (p<0.05) associated with abrogation of this correlation; comparison between the two groups revealed increased CD4:CD8 ratio in group A at 12 months (p<0.05). The histological findings according to Knodell criteria in both groups remained unchanged after 12 months follow-up. The treatment was well tolerated in all patients. CONCLUSIONS: Long-term colchicine treatment in patients with hepatic fibrosis appears to exert an anti-inflammatory, anti-fibrotic and immunomodulatory effect.

MPGN secondary to Lyme disease.

Lyme disease is a multisystem disorder with protean clinical manifestations that is caused by the tick-transmitted spirochete Borrelia burgdorferi. Infection caused by B burgdorferi is known to induce glomerulonephritis in animals. We report a patient with acute postinfection membranoproliferative glomerulonephritis after the clinical multisystem manifestation of Lyme disease, which was confirmed serologically. Although the patient was dialysis dependent for a protracted period of 5 months, the final outcome was excellent.

Focal segmental glomerulosclerosis in a patient with large bilateral asymptomatic adrenal myelolipomas.

Adrenal myelolipomas are rare benign tumors, usually discovered by chance in patients with hypertension, obesity or various endocrine disorders. Focal segmental glomerulosclerosis (FSGS) can occur as a primary disease or in a variety of secondary settings. So far, no association between the two conditions has been described. We report a case of a woman admitted for nephrotic syndrome, in which a coexistence of FSGS and bilateral large adrenal myelolipomas was revealed.

C5b-9 and adhesion molecules in human idiopathic membranous nephropathy.

BACKGROUND: Cellular immune responses and C5b-9 seem to play an important role in the pathogenesis and progression of idiopathic membranous nephropathy (IMN). The aim of the study was to investigate the role of C5b-9 and adhesion molecules in the pathogenesis of the disease. METHODS: The clinical and pathological data of 35 patients with biopsy-proven IMN were correlated with immunohistochemical findings using monoclonal antibodies against T lymphocytes, monocytes/macrophages (MM), HLA-DR antigens, C5b-9, and adhesion molecules such as alpha3beta1, LFA-1beta, and ICAM-1. RESULTS: In the glomeruli, C5b-9 deposits showed a significant correlation with the intensity of IgG and C3 deposition. The stage of the disease had a significant negative relationship with the glomerular alpha3beta1 expression. In the tubulointerstitium (TIN), the number of HLA-DR(+) cells was highly correlated with the numbers of total T lymphocytes, MM, and LFA-1beta(+) cells, as well as with the percentage of tubules with C5b-9 deposits. The extent of ICAM-1 expression in the TIN was significantly correlated with the numbers of interstitial MM, HLA-DR(+), and LFA-1beta(+) cells, as well as with the extent of tubular C5b-9 deposition. The severity of tubular atrophy and interstitial fibrosis had a relationship with the numbers of total T lymphocytes, MM, HLA-DR(+), and LFA-1beta(+) cells and with the extent of tubular C5b-9 deposition and ICAM-1 expression in the TIN. Serum creatinine (Scr) was highly correlated with the numbers of interstitial total T lymphocytes, MM, HLA-DR(+), and LFA-1beta(+) cells. Moreover, Scr had a significant relationship with the severity of tubular atrophy and interstitial fibrosis, as well as with the extent of tubular C5b-9 deposition and ICAM-1 expression in the TIN. Proteinuria was significantly correlated with the extent of tubular alpha3beta1 expression. CONCLUSIONS: In IMN, C5b-9 formation may be secondary to IgG and C3 deposition. Proteinuria may contribute to the TIN damage by altering the expression of alpha3beta1 integrins in tubular cells. De novo ICAM-1 and C5b-9 expression within the TIN as well as the activated interstitial cells may be important factors leading to renal damage and renal function impairment.