Giacomo Quattrocchio

The Fate of Aggregated Immunoglobulin A Injected in IgA Nephropathy Patients and Healthy Controls

Organ uptake of IgA-containing immunologically active material was studied in humans by intravenous (IV) injection of 131I-labeled heat-aggregated human secretory IgA (HAS-IgA) in nine patients affected by primary IgA nephropathy and 10 normal volunteers. Aggregated secretory IgA was found to be removed almost exclusively by the liver. The peak activity in liver was reached at 21.1 minutes (range, 18 to 26 minutes) in patients and 19 minutes (range, 14 to 22 minutes) in controls. The rate of increase of liver radioactivity was found to be significantly slower in patients (with a mean slope of 5.0; range, 3.4 to 7.1 v 7.6, 5.6 to 11.4; P less than 0.02). The mean liver to precordium ratio at the peak time was significantly lower in patients (mean value, 2.3; range, 1.9 to 3.1) compared with controls (mean value, 3.3; range, 2.4 to 4.0) (P less than 0.02). These data confirm the pivotal role of the liver in the removal of aggregated IgA in humans and the defective clearance capacity of this test probe in IgA nephropathy patients.

Acute pyelonephritis in adults: a case series of 223 patients

BACKGROUND Acute pyelonephritis (APN) is a common disease which rarely evolves into abscesses. METHODS We prospectively collected clinical, biochemical and radiological data of patients hospitalized with a diagnosis of APN from 2000 to 2008. RESULTS Urinary culture was positive in 64/208 patients (30.7%) and blood cultures in 39/182 cases (21.4%). Two hundred and thirteen patients were submitted to computed tomography (CT) or nuclear magnetic resonance (NMR): confirmation of APN was obtained in 196 patients (92%). Among these, 46 (23.5%) had positive urine culture, 31 (15.8%) had positive blood culture and 15 (7.6%) had positive cultures of both urine and blood. In 98 patients, either urine or blood cultures were negative, but CT/NMR were positive for APN. Fifty of the 213 patients submitted to CT/NMR (23.5%) had intrarenal abscesses: only 2 were evidenced by ultrasound examination. No differences were found between patients with positive or negative CT with regards to fever, leucocytosis, C-reactive protein, pyuria, urine cultures and duration of symptoms before hospitalization. No differences were found between patients with or without abscesses with regards to these parameters and risk factors. Patients with abscesses had a longer duration of treatment and hospitalization. CONCLUSIONS Our data suggest that in APN it is not always possible to routinely document urinary infection in a clinical setting. This finding could be explained by previous antibiotic treatment, low bacterial growth or atypical pathogens. Systematic CT or NMR is necessary to exclude evolution into abscesses, which cannot be suspected on clinical grounds or by ultrasound examination and may also develop in the absence of risk factors.

Clearance of polymeric IgA aggregates in humans.

Clearance of aggregated human secretory immunoglobulin A (AHS-IgA) was studied in nine patients affected by primary IgA nephropathy (IgAGN) and six normal volunteers from the medical staff. Samples of whole blood, erythrocytes, and serum were taken from 3 to 120 minutes after injection of 0.5 mg of 131iodine-labeled AHS-IgA. No significant radioactivity was recorded on erythrocytes. The clearance curve of AHS-IgA from the circulation, calculated by measuring trichloroacetic acid precipitable radioactivity in serum, was found to be biexponential with an initial fast component significantly prolonged in patients (mean half-time, 19.4 minutes, range, 14 to 26 minutes) compared with controls (mean, 12.2 minutes, range, 7.6 to 16.8 minutes; P less than 0.01). These data indicate that clearance of aggregated polymeric IgA does not involve the erythrocyte transport system and seems to be defective in IgAGN patients.

ACUTE PYELONEPHRITIS: ANALYSIS OF 52 CASES

Acute pyelonephritis (APN) is a frequent disease, but diagnostic approach, evolution into abscesses, and indication to hospitalization are still open problems. We have made a retrospective analysis of APN cases observed in our hospital. We identified 58 patients (pt) and selected 52 of these who presented fever and loin pain at the onset (31 were hospitalized in Nephrology and 21 in other units). Urine culture was positive in 11/48 cases (22.9%), blood cultures in 3/26 cases (11.5%) (Escherichia coli). Renal sonography was normal in 20/48 cases (41.6%) and suggestive for APN in 23/48 cases (47.9%). CT with contrast medium was normal in 9/28 cases (32.1%) and positive in 19/28 cases (67.8%), with evidence of unique or multiple hypodense areas; abscesses were found in 8 patients (28.5%). No statistically significant differences were found between patients with positive or negative CT as regards fever, leukocytosis, ESR, CRP, CRP at 20 days, urinary leukocytes, urine culture, duration of symptoms before hospitalization. Moreover no differences were found between patients with and without abscesses. CT was performed more frequently among patients hospitalized in Nephrology than among patients hospitalized in other services (24/31—77.4%—vs. 4/21—19%—, p = 0.05). NMR was abnormal in 6/9 cases. A radiographic documentation of APN was obtained in 61.53% of patients with clinical diagnosis of APN. Of these, only 18.7% had positive urine culture. In conclusion, our data suggest that demonstration of urine infection is not necessary for APN diagnosis, when clinical and/or radiologic diagnosis of APN has been made. Evolution into abscesses is frequent and not easily susceptible on clinical ground; for this reason we think it is advisable to perform CT or NMR systematically. Differences in clinical behavior between different units suggest the need for diagnostic guidelines.

Rituximab therapy for IgA-vasculitis with nephritis: a case series and review of the literature.

Henoch–Schonlein purpura, also called IgA-vasculitis, is a systemic small vessels vasculitis with immunoglobulin A1-dominant immune deposits. The optimal treatment remains controversial. Because IgA-vasculitis is characterized by leukocyte infiltration of the blood vessel walls along with immunoglobulin A deposition, and because glucocorticosteroids inhibit inflammatory processes, early administration of glucocorticosteroids has been postulated to be effective, but this indication remains controversial. Immunosuppressive agents (azathioprine, cyclophosphamide, cyclosporine, mycophenolate) have been used in combination with glucocorticosteroids without definitive evidence of effectiveness. The efficacy of rituximab in adult IgA-vasculitis has been reported in few cases. We described a monocentric experience on the use of rituximab in adult IgA-vasculitis with biopsy-proven nephritis. The patients achieved a complete remission of nephritis and syndromic manifestations, and no patients experienced adverse reactions. These data have been compared with the limited literature nowadays available.

IgG4-related nephropathy

Abstract IgG4-related disease (IgG4-RD) is a recently recognized disorder, often with multiple organ involvement, characterized by dense tissue infiltration of IgG4-positive plasma cells, storiform fibrosis, obliterative phlebitis and frequently elevated serum IgG4 concentration. The kidney can be involved either directly or indirectly. The most frequent direct renal manifestations of IgG4-RD are IgG4-related tubulointerstitial nephritis (TIN) and membranous glomerulonephropathy. Retroperitoneal fibrosis (RPF) is another condition that is frequently IgG4-related and that can indirectly affect the kidney causing ureteral obstruction and hydronephrosis. Contrast-enhanced computerized tomography, magnetic resonance imaging and 18F-fluorodeoxyglucose positron emission tomography/computed tomography show different imaging findings and are useful tools for monitoring therapeutic response. Steroid treatment is the first line of therapy, but relapsing or refractory forms of the disease are frequently observed and require more aggressive therapeutic approaches. At our centre, we treated three cases of aggressive IgG4-related TIN and two cases of IgG4-related RPF with an intensified, immune suppressive protocol, obtaining good results without severe adverse effects.

Renal biopsy in patients over 75: 131 cases.

Introduction: Demographic analysis shows the ageing of the global population and the consequent increase in the age of hospitalized subjects and of patients starting dialysis. Hence, interest in the feasibility, safety, and usefulness of renal biopsy in elderly patients is growing. We examined the data of 131 patients over the age of 75 who underwent renal biopsy. We analyzed the safety of the procedure, treatment, and outcomes. Results: Histological diagnoses included: membranous glomerulonephritis (GN) 20.6%, crescentic GN 12.9%, IgAGN 10.6%, focal segmental glomerulosclerosis 9.1%, acute GN 4.5%, amyloidosis 9.1%, and acute tubular necrosis 3.8%. Mean glomerular obsolescence was 28.9 ± 27.9%. Mean age of the patients was 78.7 ± 5.73 years. At the time of biopsy, serum creatinine (SCr) was 4.47 ± 2.56 mg/dL and proteinuria was 4.82 ± 6.78 g/day. Targeted treatment was given to 51.9% of patients, 52.9% of whom had a good clinical response. Eight patients had clinically non-relevant side effects (11.7%). A positive response (defined as a more than 50% reduction of SCr, or by partial or complete remission of proteinuria) was observed in 36 patients (52.9%). 76 patients were monitored for 57 ± 9.89 months: 18 patients were on dialysis (follow-up 2.56 ± 3.61 months), 15 died (follow-up 58.5 ± 13.43 months), and 52 remained under nephrologic observation for 36 ± 31 months (SCr was 2.56 ± 0.75 mg/dL and proteinuria was 4.82 ± 6.78 g/day). Conclusion: In our experience, renal biopsy is safe even in very elderly patients; it allowed targeted treatment in 51.9% of patients, 52.9% of whom had a good clinical response, possibly contributing to prolonged patient survival and improved quality of life.

Is it possible to diagnose primary anti-phospholipid syndrome (PAPS) on the basis of renal thrombotic microangiopathy (PAPS nephropathy) in the absence of other thrombotic process?

The kidneys are a major target of PAPS. The histologic lesions of PAPS nephropathy are vascular; among them thrombotic microangiopathy (TMA) is the most characteristic. It is still not clear in the literature whether the nephropathy can be the unique manifestation of PAPS in the absence of other thrombotic processes; that is: do the renal microthrombotic lesions allow to make the diagnosis of PAPS in presence of anti-phospholipid antibodies (APA)? With this purpose we present three clinical cases. The first patient had severe hypertension C4 hypocomplementemia, thrombocytopenia, and mitralic valve insufficiency. LAC and anti-cardiolipin antibodies at high titre were positive. The histologic picture was characterized by basement membrane reduplication and arteriolar mucoid degeneration, which are features of early phase of TMA. The second patient had severe hypertension. The detection of anti-cardiolipin antibodies was performed several times and resulted positive three times, four months after the diagnosis as well. The renal histologic features were consistent with late lesions of TMA. The third patient had severe hypertension, rapidly progressive renal failure, tricuspidal valve insufficiency and two positive anti-phospholipid antibodies determinations three weeks apart (in two occasions anti-cardiolipin and in one occasion LAC as well were found). The renal lesions were characteristic for TMA. In conclusion we think that patients with TMA and anti- phospholipid antibodies can be considered affected by PAPS, as the thrombotic process is represented by thrombosis in preglomerular arterioles, which leads to TMA.

lndium-111-Labeled Granulocyte Head Accumulation in Patients with Wegener’s Granulomatosis

Among the symptoms of systemic vasculitis, purulent rhinorrhea with painful sinusitis is thought to be relatively specific to Wegener’s granulomatosis (WG). Sixteen patients with rapidly progressive g

Retroperitoneal fibrosis and schistosomiasis: A causal relationship?

Retroperitoneal fibrosis (RPF) is characterized by replacement of the normal tissue of the retroperitoneum with fibrosis and/or chronic inflammation. About two-thirds of cases of RPF are idiopathic and one-third is secondary to drugs, infections (tuberculosis, syphilis, actinomycosis, fungal infections), retroperitoneal hemorrhage, or malignancy. We report the case of a patient who was diagnosed as having RPF and schistosomiasis caused by Schistosoma haematobium with histological documentation. He was treated with praziquantel and afterwards with corticosteroids with remission of RPF. To our knowledge, the association between schistosomiasis and RPF has not been described in the literature. We postulate that there is a causal relationship between these two conditions.