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Background We aimed to investigate the safety and efficacy of an intensified B-cell depletion induction therapy (IBCDT) without immunosuppressive maintenance regimen compared with standard of care in biopsy-proven lupus nephritis (LN). Methods Thirty patients were administered an IBCDT (4 weekly rituximab [RTX] 375 mg/m2 and 2 more doses after 1 and 2 months; 2 infusions of 10 mg/kg cyclophosphamide [CYC], 3 methylprednisolone pulses), followed by oral prednisone (tapered to 5 mg/d by the third month). No immunosuppressive maintenance therapy was given. Thirty patients matched for LN class and age were selected as controls: 20 received 3 methylprednisolone pulses days followed by oral prednisone and mycophenolate mofetil (MMF) 2 to 3 g/d, whereas 10 were given the Euro Lupus CYC. MMF (1-2 g/daily) or azathioprine (AZA, 1-2 mg/kg/day) were given for > 3 years as a maintenance therapy. Results At 12 months, complete renal remission was observed in 93% of patients on IBCDT, in 62.7% on MMF, and in 75% on CYC (P = 0.03); the dose of oral prednisone was lower in the IBCDT group (mean ± SD 2.9 ± 5.0 mg/dl) than MMF (10.5 ± 8.0 mg/d, P < 0.01) or CYC group (7.5 ± 9.0 mg/d, P < 0.01). Mean follow-up after treatment was 44.5 months (interquartile range [IQR] 36–120 months), 48.6 months (IQR 36–120 months), and 45.3 (IQR 36–120 months) for IBCDT, MMF, and CYC, respectively. At their last follow-up visit, we observed no significant differences in proteinuria and serum creatinine, nor in the frequency of new flares among the 3 groups. Conclusion In biopsy-proven LN, the IBCDT without further immunosuppressive maintenance therapy was shown to be as effective as conventional regimen of MMF or CYC followed by >3-year maintenance either MMF or AZA regimen. Moreover, the use of IBCDT was associated with a marked reduction of glucocorticoid cumulative dose., Graphical abstract

IgG4-related disease (IgG4-RD) is an immune-mediated disorder often showing elevated serum IgG4 concentrations, dense T and B lymphocyte infiltration, and IgG4-positive plasma cells and storiform fibrosis. We prospectively evaluated for 4 years 5 patients with histologically proven IgG4-RD of whom 3 had tubulointerstitial nephritis (TIN) and 2 had retroperitoneal fibrosis (RPF). They received an intensive B depletion therapy with rituximab. The estimated glomerular filtration rate of TIN patients after 1 year increased from 9 to 24 ml/min per 1.73 m2. IgG/IgG4 dropped from 3236/665 to 706/51 mg/dl, C3/C4 went up from 49/6 to 99/27 mg/dl, and the IgG4-RD responder index fell from 10 to 1. CD20+ B cells decreased from 8.7 to 0.5%. A striking drop in interstitial plasma cell infiltrate as well as normalization of IgG4/IgG-positive plasma cells was observed at repeat biopsy. Both clinical and immunological improvement persisted over a 4-year follow-up. Treating these patients who were affected by aggressive IgG4-RD with renal involvement in an effort to induce a prolonged B cells depletion with IgG4 and cytokine production decrease resulted in a considerable rise in eGFR, with IgG4-RD RI normalization and a noteworthy improvement in clinical and histological features. Furthermore, the TIN subgroup was shown not to need for any maintenance therapy.

Patients (pts) with primary Membranous nephropathy (MN) have an autoimmune disease caused by autoantibodies against podocyte antigens and 60-80% of them have antibodies directed against the M-type phospholipase A2 receptor (PLA2R). Immunosuppressive treatment is recommended in high-medium risk pts. Recently the use of rituximab (RTX), has emerged as an important therapeutic option in pts with primary MN. The appropriate cumulative dose of RTX in PMN pts is still uncertain, and favorable outcomes even with low-dose of RTX has been described. We compared efficacy and safety of 3 different treatment regimens: low-dose RTX (Protocol 1, one dose of RTX 375 mg/m2), standard RTX protocol (Protocol 2, four weekly doses of rituximab 375 mg/m2) and Ponticelli’s regimen. 42 pts with primary MN and nephrotic syndrome were assigned to Protocol 1 (14 pts) or Protocol 2 (14 pts). All patients were followed for 24 months after RTX. Fourteen pts, matched for age and baseline serum creatinine (sCr) and proteinuria, treated with Ponticelli’s regimen were examined as controls. At 24 months, a significant improvement in proteinuria levels was observed in pts treated with Protocol 1 (7.5 ± 4.8 at T0; 0.21 ± 0.15 at T24, p

AL amyloidosis is caused by a clone of plasma cell. Due to the impact of the disease on patient survival, careful evaluation of organ involvement is essential and treatment should be tailored to single patient's risk. AIM: We analyzed the clinical, laboratory and histological characteristics of 21 elderly patients (pts) (mean age 74.7 ± 7.97 years, range 55–81) with AL amyloidosis, including 17 patients (81%) with biopsy-proven renal involvement, who were ineligible for bone marrow transplantation, and evaluated the impact of renal impairment on survival. Cardiac and renal involvement was found in 14 (67%) cases. Among the 17 patients with renal involvement, 12 had renal failure with proteinuria, and one showed isolated renal failure and vascular amyloid deposition. Hematological response occurred in 57.1% after first line therapy (75% after three cycles). In six of the patients with renal involvement, proteinuria decreased from 4.2 to 1.1 g/24 h (range 0.2–3 g/24 h), serum Creatinina (sCr) levels declined or stabilized. Severe renal failure at diagnosis was found to directly influence patient survival, while the Staging System for Renal Outcome in AL Amyloidosis did not associate with outcomes. To the best of our knowledge this is the first case series in which the whole cohort of patients with urinary or functional abnormalities underwent a histological evaluation. None of the patients were eligible for bone marrow transplantation. Hematologic response was 57.1%, while renal response was much lower (35%). Of note, the Staging System did not completely apply to this peculiar setting of patients in whom renal involvement was not presumptive but biopsy-proven. More aggressive approaches may be needed in these patients to avoid the inexorable progression of the disease.

Rituximab (RTX), an anti-CD20 monoclonal antibody, has shown to be an effective induction treatment for small-vessel vasculitides associated with antineutrophil cytoplasm antibodies (AAV) in both newly diagnosed and relapsing patients. However, the role of RTX in the management of the most severe cases of AAV remains to be fully elucidated. The aim of this study was to assess both safety and efficacy of an intensified B-cell depletion therapy (IBCDT) protocol, including RTX, cyclophosphamide (CYC), and methylprednisolone pulses without additional maintenance immunosuppressive therapy in a cohort of 15 AAV patients with the most severe features of AVV renal involvement (as

Patients with multiple myeloma often have kidney involvement with acute kidney injury which is frequently due to cast nephropathy. Hemodiafiltration with endogenous reinfusion (HFR) allows removal from the circulation of significant amounts of free light chains (FLCs) responsible for tubular damage.Between 2014 and 2018, 13 patients affected by multiple myeloma (64% λ chain and 36% k), including 10 cases with biopsy-proven cast nephropathy, were treated with this technique. Each patient had high free light chains levels at diagnosis: median 8586 mg/l for λ and 4200 mg/l for k, and stage III acute kidney injury (median serum creatinine 7.5 mg/dl). We initially performed daily HFR-Supra sessions and then modulated them based on renal response (mean 10 sessions/patient). At the same time, the patients also received various chemotherapy regimens, depending on their hematological criteria.Forty-six percent of patients showed at least partial renal function recovery within the third month, thus allowing dialysis discontinuation; 38% remained on dialysis. Two patients died. The mean reduction rate of free light chains at the end of the HFR-Supra cycle was 85% (k) and 40% (λ), respectively. Serum albumin remained stable during the whole treatment.In our experience, the synergistic effect of chemotherapy and HFR-Supra led to a recovery of renal function in 6 out of 13 patients presenting with severe dialysis-requiring acute kidney injury. HFR-Supra allowed stable albumin levels, with high free light chains removal rate, at a relatively low costs.

Background and Aims IgA-vasculitis (IgAV) is a systemic small vessels vasculitis characterized by deposition of underglycosylated IgA1 immune complexes. Renal involvement indicates severity of illness and chronic kidney disease represents the most serious long-term complication of IgAV. Presently, no treatment is specifically recommended in IgAV Glucocorticoids (GC) have been traditionally thought to be effective in tempering systemic symptoms, but did not show long-term benefits either in reducing flares or progression of kidney disease. The effectiveness of conventional immunosuppressants is controversial. Recently Rituximab (RTX) has been proved to be effective in a few case series of adults with IgAV. However, long term results are lacking. Aim of the study: to evaluate the effectiveness of RTX as first line therapy in induction and maintenance of remission of adults with IgAV with biopsy-proven crescentic glomerulonephritis. Method We reviewed the clinical records of patients with adult-onset IgAV treated with RTX at our Center. Patients included 8 males and 4 females, mean age 45 years (range 19-75) with mean follow-up duration of 31 months (range 6-144). Diagnosis was based on the combination of clinical assessment, serological tests and histological analysis according to EULAR criteria. All patients (pts) had a biopsy proven IgAV- severe nephritis. RTX was given for the treatment of relapsing or refractory disease or because of definite contraindications to standard dose CS and/or conventional immunosuppressants. Patients received 4 weekly doses of RTX (375 mg/m2) given alone (8 pts) or in combination with CS (4 pts). Disease activity was evaluated by Birmingham Vasculitis Activity Score version 3 at the onset and at 1, 6 and 12 months and at the end of follow up. Complete remission (CR) was defined as BVAS of 0 Results Eleven pts (91.7%) achieved a clinical response at 6 months. Ten pts had a CR while 1 pt had a partial response and was given an additional dose of RTX after 12 months from induction due to persistent proteinuria (1gr/24 hrs), despite systemic remission. He achieved a CR 6 months later. One patient did not respond to RTX and was switched to MMF. Among the 10 pts with CR, 1 patient needed maintenance doses of RTX every 6 months due to relapse of palpable purpura; 1 relapsed after 15 months and received a new induction course showing a CR again. Significant decrease in 24-hour proteinuria (P = 0.043), BVAS (P = 0.031),and CRP level from RTX initiation through the last follow-up visit was detected. RTX was generally well tolerated. One patient, who had a CR with RTX alone died after 6 months of follow-up for cardiovascular cause. Conclusion This extended experience confirms our initial results supporting the use of RTX in the treatment of IgAV with severe renal involvement. Indeed, RTX proved to be effective and safe for induction and maintenance of long-lasting remission. Present data also suggest that RTX is not only effective for severe and refractory IgAV, but can be also proposed as a first line therapy.

Background and Aims Immunoglobulin light chain amyloidosis (AL) with multi-organ involvement is characterized by poor outcome. Current treatment of AL targeting the underlying plasma cell clone has been adapted from the multiple myeloma (MM). Novel powerful drugs are expanding the therapeutic options. Daratumumab is a first-in-class anti-CD38 human antibody (IgG1κ) which proved to be effective in combination with bortezomib in MM refractory to conventional bortezomib-based regimens. Its effectiveness as a single agent and its safety in the treatment of AL amyloidosis is under study. Aim of the study: This study reports the experience with Daratumumab monotherapy in a series of severe patients with AL amyloidosis and multiorgan and biopsy-proven renal involvement. Method Five patients (2 males and 3 females), mean age 64 years (range 52-69) were treated with Daratumumab following antibody testing and extended RBC antigen phenotyping. Treatment protocol was as follows: 16 mg/kg Daratumumab i.v. administered weekly for 8 weeks, then 8 times every two weeks, and then monthly for 1 year. Premedication included oral paracetamol, and i.v. chlorphenamine and methylprednisolone. Results In patient #1, in dialysis, who was refractory to conventional therapies Daratumumab administration resulted in normalization of the FLC ratio with disappearance of serum M-component and Bence-Jones (BJ) proteinuria. In patient #2 who had a relapsing disease, Daratumumab treatment resulted in a rapid decrease of proteinuria (from 6.8 to 2.7gr/24 hours at the 16th dose) and N-terminal propeptide (NT-pro-BNP) levels (from 1844 pg/ml to 330 pg/ml) with disappearance of serum M-component and BJ proteinuria and normalization of the FLC ratio. Patient #3 was treated front-line. He had an impressive decrease of proteinuria from 9.3 to 2.2 gr/24 hrs and NT-proBNP levels (from 850 pg/ml to 225 pg/ml) with normalization of FLC ratio and disappearance of serum M-component. In patient #4, who was intolerant to conventional regimens, Daratumumab therapy resulted in decrease in proteinuria, disappearance of serum M-component and improvement in the FLC ratio, which were paralleled by a reduction of NT-proBNP levels. Patient #5 had a relapsing disease. Daratumumab achieved a decrease of proteinuria (from 2.5 to 1 gr/24 hrs9, a decrease of serum M-component with increase of FLC ratio (0.29, nv: 0.31 – 1.56). This was the only patient who experienced an infusion reaction during the first dose (grade 1). The 4 patients with still preserved renal function also showed renal response with sCr improvement or stabilization and a decrease in proteinuria levels These data were paralleled by the reduction of NT-proBNP values in the 3 patients with cardiac involvement. Conclusion Daratumumab monotherapy resulted in the disappearance of M-proteins in every patient with FLC ratio normalization in 4 out of 5 subjects and impressive decrease of proteinuria and pro-BNP values proving to be an effective therapeutic option for pretreated/naïve patients with severe AL with renal involvement.

Background and Aims: Many patients with End Stage Kidney Disease do not undergo percutaneous kidney biopsy (KB) and do lack a definite diagnosis. Whether KB is beneficial in the extreme patients’ categories, i.e., age >75 years and very late referrals with kidney disease requiring renal replacement therapy at the first evaluation, remains controversial. Aim: To analyse the benefit/risk balance in terms of therapeutic options and general outcome of KB procedure in these borderline categories. Method Files for all biopsies performed in our Centre between 2013 and 2019 (# 903 inpatients’ native kidney) were retrospectively analysed with special focus on histological diagnosis, biopsy complications, and post-biopsy patient’s outcome. Two groups of high risk patients were identified 1. >75 years old patients, and 2. patients requiring dialysis at the first clinical evaluation. A rigorous protocol of screening of the bleeding risks was adopted. Results Of the 903 biopsies, 217 cases (24%) had group 1, and 92 (10%) group 2 criteria. Group 1: mean age 80 years (range 75-92), main histological diagnoses: ANCA associated vasculitis (AAV) (12,4%); membranous nephropathy (MN) (11,5%), diabetic nephropathy (10,1%), IgA glomerulonephritis (IgAGN) (9,2%), cast nephropathy (9,2%), renal amyloidosis (9.2%), focal segmental glomerulosclerosis (FSGS - 7,8 %). Group 2: mean age 60 years (range 20-92), most frequent histological diagnosis: AAV (26,1%); cast nephropathy (19,6 %), nephroangiosclerosis (9,8%), IgAGN (7,6 %), diabetic nephropathy (6,5%), renal amyloidosis (5,4%); FSGS (4,3%). Five major complications (2,3%), including AV fistula with spontaneous resolution in 4 patients and 1 case of severe bleeding requiring arterial embolization, and 14 minor complications (6,5%), including post biopsy haematomas Conclusion Given its high diagnostic value (especially in patients who are willing to be transplanted), the prognostic significance (and the assessment of the extent of the renal sclerotic changes), and the potential impact on the treatment policy, indications to percutaneous kidney biopsy in elderly and dialysis patients should be probably revised.

Immunoglobulin-A vasculitis (IgAV) is a systemic small-vessel vasculitis in which renal involvement indicates severity of illness, and chronic kidney disease represents the most serious long-term complication. No treatment at present is specifically recommended for IgAV. Recently, rituximab (RTX) has been shown to be effective in case series of adults with IgAV. However, long term results are lacking. Aim of the study is to evaluate the effectiveness of RTX as induction therapy and maintenance of remission in adults with severe IgAV and aggressive glomerulonephritis.This study included 12 adult-onset patients, 8 males and 4 females, mean age 45.1 years (range 19-75) with a mean follow-up duration of 33.7 months (range 6-144). All patients had a severe IgAV with biopsy proven crescentic nephritis. RTX was given for the treatment of a refractory disease or because of definite contraindications to standard therapies.Eleven patients (91.7%) achieved a clinical response at 6 months. Ten patients had a complete response (CR) while one had a partial response and was given an additional dose of RTX after 12 months for persistent proteinuria (1gr/24 hrs) despite systemic remission. He achieved a CR 6 months later. One patient was considered unresponsive to RTX and was switched to MMF. Among the 10 patients with CR, 1 needed maintenance doses of RTX every 6 months for iterative relapsing of severe purpura, 1 relapsed after 15 months and received a new induction course showing a CR again. A significant decrease in BVAS (p=0.031) and 24-hour-proteinuria (p=0.043) from RTX initiation through the last follow-up has been detected. One patient, who had a CR with RTX alone died after 6 months for therapy-unrelated cardiovascular cause.RTX proved to be effective and safe for induction and maintenance of long-lasting remission in severe IgAV with aggresive renal involvement. Data also suggest that RTX can be indicated not only for refractory cases, but can be also proposed as a first line therapy.

Background:B cells play a key role In the pathogenesis of Lupus Nephritis (LN).Objectives:we aim to investigate the safety and efficacy of an intensified B-cell depletion induction therapy (IBCDT)without immunosuppressive maintenance regimen compared to standard of care in biopsy-proven LN.Methods:Thirty patients were administered an IBCDT (4 weekly Rituximab 375mg/m2 and 2more doses after 1&2 months;2 infusions of 10 mg/kg cyclophosphamide (CYC),3 methylprednisolone pulses), followed by oral prednisone (tapered to 5 mg/day by the 3rd month). No immunosuppressive maintenance therapy was given. Thirty patients matched for LN class and age were selected as controls: 20 received 3 methylprednisolone pulses days followed by oral prednisone and mycophenolate mofetil (MMF) 2-3 g/day, while 10 were given the Euro Lupus CYC.Results:At 12 months, complete renal remission was observed in 93% of patients on IBCDT, in 62.7% on MMF, and in 75% on CYC (p=0,03); the dose of oral prednisone was lower in the IBCDT group (mean±SD 2.9±5.0mg/dl) than MMF (10.5±8.0 mg/day,pConclusion:In biopsy proven LN, the IBCDT without further immunosuppressive maintenance therapy was shown to be as effective as conventional regimen of MMF or CYC followed by a 3-year maintenance MMF regimen. Moreover, the use of IBCDT was associated with a marked reduction of glucocorticoid cumulative dose.Disclosure of Interests:None declared

Immunoglobulin light chain amyloidosis is a rare systemic disease caused by monoclonal light chains (LCs) depositing in tissue as insoluble fibrils resulting in irreversible damage of vital organs. The mechanisms involved in aggregation and deposition of LCs are not fully understood, but CD138/38 plasma cells are undoubtedly involved in monoclonal LC production. We are reporting favorable effects on AL amyloidosis patients with renal involvement using the anti-CD38 monoclonal antibody Daratumumab. We speculate that research for the near future should be devoted to design similar therapeutic approaches for other diseases attributable to a plasma cell dyscrasia.

Immunoglobulin light chain amyloidosis (AL amyloidosis) is a rare systemic disease characterized by monoclonal light chains (LCs) depositing in tissue as insoluble fibrils, causing irreversible tissue damage. The mechanisms involved in aggregation and deposition of LCs are not fully understood, but CD138/38 plasma cells (PCs) are undoubtedly involved in monoclonal LC production.CD38 is a pleiotropic molecule detectable on the surface of PCs and maintained during the neoplastic transformation in multiple myeloma (MM). CD38 is expressed on T, B and NK cell populations as well, though at a lower cell surface density. CD38 is an ideal target in the management of PC dyscrasia, including AL amyloidosis, and indeed anti-CD38 monoclonal antibodies (MoAbs) have promising therapeutic potential. Anti-CD38 MoAbs act both as PC-depleting agents and as modulators of the balance of the immune cells. These aspects, together with their interaction with Fc receptors (FcRs) and neonatal FcRs, are specifically addressed in this paper. Moreover, the initiallyavailable experiences with the anti-CD38 MoAb DARA in AL amyloidosis are reviewed.

Minimal change disease (MCD) accounts for 15% of adult nephrotic syndrome (NS) cases. Adult-MCD patients may have more severe clinical features than pediatric patients. In children, Rituximab (RTX) has been used since 2006 to treat frequently relapsing NS. In adults, data about the efficacy of RTX for MCD are limited. We report our experience on the use of RTX in adult biopsy-proven MCD. Our series includes 6 adult patients (2 males and 4 females), age 45-73 years, treated with RTX (4 weekly doses of 375 mg/m2). Proteinuria decreased from 11,2 (23-4.8) g/24 hours to 0.6 (0-2) g/24 hours after 6 months, and to 0.4 (0-1, 4) g/24 h in the 4 pts with the longer follow-up. Creatinine decreased from 1.95 (0.5-5) mg/dl to 0.88 (0.6-1.3) mg/l. Five patients achieved a complete renal remission, while in 1 pt proteinuria decreased by 75%. RTX successfully depleted CD19 lymphocytes in 100% of pts for at least 6 months. No clinically relevant adverse events have been observed. This case series shows a remarkable efficacy of RTX in treatment of MCD. RTX can be an attractive alternative both in recurrent forms and in induction-therapy of MCD. RTX may be preferentially used in patients at a high risk of development of the adverse effects of corticosteroids and should be considered as an alternative option in patients with recurrent NS. Additional data are needed to inform clinical practice on how best to use RTX in this patient population, so that definitive randomized trials can be planned.

IgG4-related disease (IgG4-RD) is a recently recognized disorder, characterized by elevated serum IgG4 concentrations, dense tissue infiltration of IgG4-positive plasma cells and storiform fibrosis. Treatment is usually based on steroids, however, relapses and long-term adverse effects are frequent. We prospectively studied 5 consecutive patients with histologically-proven IgG4-RD and renal involvement, treated with an extended Rituximab protocol combined with steroids. Two doses of intravenous cyclophosphamide were added in 4 patients. Five patients with IgG-RD were investigated: three had tubulointerstitial nephritis (TIN), while two had retroperitoneal fibrosis (RPF). In the patients with TIN, renal biospy was repeated after 1 year. In the patients with TIN, estimated glomerular filtration rate (eGFR) at 12 months increased from 9 to 24 ml/min per 1.73 m2; IgG/IgG4 decreased from 3,236/665 to 706/51 mg/dl; C3/C4 increased from 49/6 to 99/27 mg/dl; CD20+ B-cells decreased from 8.7% to 0.5%; Regulatory T-cells decreased from 7.2% to 2.5%. These functional and immunologic changes persisted at 24 months and in two patients at 36 months. A repeat renal biopsy in the patients with TIN showed a dramatic decrease in interstitial plasma cell infiltrate with normalization of IgG4/IgG positive plasma cells. The patients with RPF showed a huge regression of retroperitoneal tissue. In this sample of patients with aggressive IgG4-RD and renal involvement, treatment aimed at depleting B cells and decreasing antibody and cytokine production was associated with a substantial, persistent increase in eGFR, and a definite improvement in immunologic, radiologic and histological parameters.

Acute pyelonephritis is a common disorder prevalently affecting young women, that may be severe in the elderly, in diabetics, in pregnant women and in immunosuppressed patients. The aim of this chapter is to try to elucidate some nebulous points, also through our own experience, regarding the relationship with vesico-ureteral reflux in adults, the frequency of complication with abscesses, the need for CT or magnetic resonance imaging, the long-term evolution. Acute pyelonephritis (APN) in the native kidney is a common disorder prevalently affecting young women. It is responsible for more than 100,000 hospitalizations per year in the U.S. APN is usually a benign disease, but it may be severe in the elderly, in diabetics, in pregnant women, and in immunosuppressed patients. Complicated APN may present renal abscesses or transformation into emphysematous pyelonephritis (EP). A pathogenic role is played by sexual activity, genetic predisposition, and urinary instrumentation. The correlation between APN and vesicoureteral reflux (VUR) in adults has not been clearly determined. The most common etiologic agent both in adults and in children is Escherichia coli. Diagnosis of APN is mainly clinical, but only CT or magnetic resonance are able to establish the exact definition and extent of the renal parenchymal lesions and to detect abscesses. The frequency of abscesses is largely underestimated in the literature and in clinical practice. The most severe cases of APN should be treated, at least at the onset, with parenteral antibiotics, and the patients should be hospitalized. Antibiotic treatment should include fluoroquinolone or a broad spectrum cephalosporin associated or not with an aminoglycoside for 10–14 days. Abscesses require longer treatment, and drainage may be necessary in large ones. The long-term evolution of APN seems favorable, even though cortical scar formation, development of proteinuria, or renal failure have been reported.

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 Â ± 27.9%. Mean age of the patients was 78.7 Â ± 5.73 years. At the time of biopsy, serum creatinine (SCr) was 4.47 Â ± 2.56 mg/dL and proteinuria was 4.82 Â ± 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 Â ± 9.89 months: 18 patients were on dialysis (follow-up 2.56 Â ± 3.61 months), 15 died (follow-up 58.5 Â ± 13.43 months), and 52 remained under nephrologic observation for 36 Â ± 31 months (SCr was 2.56 Â ± 0.75 mg/dL and proteinuria was 4.82 Â ± 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.

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.

Acute renal infarction is a rare condition whose diagnosis is often delayed. Major risk factors include atrial fibrillation, valvular or ischemic heart disease, renal artery thrombosis/dissection and coagulopathy. We reviewed the medical records of 18 patients admitted to our Nephrology Department between 1999 and 2015 for acute renal infarction diagnosed by computed tomography. Tc-99m dimercaptosuccinic acid (DMSA) scintigraphy was performed in some patients during follow-up to assess parenchymal lesions and estimate differential kidney function. Mean age was 59.8 years. Major associated risk factors included hypertension (44 %), obesity (33 %), atrial fibrillation (28 %), peripheral vascular disease (17 %), smoking (17 %), prior thromboembolic event (11 %), diabetes (11 %), estroprogestinic therapy (11 %). Seventy-two percent of patients presented with flank pain. Mean serum creatinine was 1.2 ± 0.6 mg/dl. Acute kidney injury occurred as the initial manifestation in two patients. Patients were managed conservatively, with low molecular weight heparin (83 %) or aspirin (11 %). At the end of follow-up serum creatinine was 1.1 ± 0.3 mg/dl; one patient remained on chronic hemodialysis. 58 % of patients who underwent renal scintigraphy after a median of 8 months had a reduced contribution of the previously affected kidney to total renal function. Risk factors associated with the development of chronic kidney disease following renal infarction are unknown. In our subjects, renal function remained stable in all but one patient who developed end stage renal disease. Further studies should focus on etiology and evolution of kidney function in patients with acute renal infarction.

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 antiphospholipid antibodies can be considered affected by PAPS, as the thrombotic process is represented by thrombosis in preglomerular arterioles, which leads to TMA.

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.

In 2012, the Piedmontese Clinical Nephrology Group retrospectively analyzed a cohort of patients diagnosed with focal and segmental glomerulosclerosis (FSGS) in Piedmont and the Aosta Valley, with a special focus on frequency of disease, choice and duration of treatment at disease onset and during relapses. Seventeen centers participated. The total number of FSGS cases was 467: 148 were diagnosed between 1991 and 2000 and 319 between 2001 and 2010, corresponding to a 127% increase in the latter decade. First-line treatment in 9 centers was full-dose corticosteroid (CS) for 4 months with 8 centers using CS for 2-3 months. One center used additional iv CS pulse treatment. Dosage tapering lasted 3-9 months; in one center dose tapering lasted for less than 3 months. During first relapse, 10 centers used CS as drug of choice, 4 centers CS and cyclosporin (CyA), 3 centers CS and cyclophosphamide (CyF), with one center using chlorambucil instead of CyF. In 2 centers CyA or CyF were each considered appropriate and employed on an individual basis. Only one center considered mycophenolate (MMF) as a treatment option. If multiple relapses occurred, 14 centers chose CyA as drug of choice, 2 centers CyF (in association with low-dose CS) and 1 center did not report any multiple relapses. Eight centers proposed a variation in therapeutic approach: MMF (5), Rituximab (3), Tacrolimus (1), CyF (1), ACTH (1). If CS dependence occurred, the maximum dose allowed was considered to be 15 mg/day in 2 centers, 12.5 mg/die in 4 centers, 10 mg/die in 4 more centers, 7.5 mg/die in 1 center, and 5 mg/die in a further one. Three centers did not refer any experience with CS dependence. Only 4 centers had direct experience with MMF and maintained treatment for about 3 years. In relapsing cases with a good response to CyA, the drug was discontinued after 5 years in 2 centers, after 3 years in 2 centers, 2 years in 4 centers, 1 year and a half in 2 centers, and 1 year in 3 centers. CyA was used as a long-term treatment in 3 centers. In conclusion, Piedmontese nephrologists followed K-DOQI guidelines in typical cases of FSGS. When the disease presents with an atypical course nephrologists' decisions appeared to be influenced by their experience with atypical drugs, such as MMF and Rituximab. Studies with other drugs are needed to improve the prognosis of forms of FSGS resistant to current treatments, which have remained virtually unchanged since the 1970s.

Acute pyelonephritis (APN) is a frequent pathological condition. Its etiology is prevalently due to E. coli and risk factors include sexual activity, genetic predisposition, old age and urinary instrumentation. No correlation between APN and vesicoureteral reflux has been established in adults. The diagnosis of APN is usually clinical, but computed tomography (CT) and magnetic resonance imaging (MRI) allow a more precise definition and can document evidence of abscesses. Severe cases should be treated with a fluoroquinolone or an extended-spectrum cephalosporin. Treatment should last 10-14 days. The long-term evolution of APN is prevalently favorable in adults, even though formation of cortical scars and development of macroalbuminuria and renal failure have been described. The formation of renal abscesses is underestimated and must be evaluated by CT or MRI. Abscesses need to be drained only when they are large, and medical treatment is successful in the majority of cases.

The Piedmont Group of Clinical Nephrology has compared the activity of 18 nephrology centers in the region Piedmont/Valle d'Aosta with regard to renal biopsy (RB). Data on the RBs performed in every nephrology unit, taking into account their entire experience (in some cases spanning more than 30 years), were analyzed. 3396 RBs were performed between 1996 and 2011. Thirty to forty percent were done in patients aged-65 years (1568 in patients-65 years, 29 in patients-85 years). 598 BRs were performed in children over the last 20 years. The following contraindications to RB were considered: chronic renal failure by 8 centers (44.4%), serum creatinine (SCr3 mg/dL) by 3 centers, longitudinal renal size8 cm by 3 centers, and renal cortex thickness1 cm by 2 centers. 1798 RBs were performed in patients with SCr2 mg/dL and 275 in patients on dialysis. The percentage of RBs performed in patients with SCr2 mg/dL ranged from 27% to 55% between centers. As regards RB in the course of acute renal failure in an ANCA-positive context, 4 centers allowed administration of corticosteroids and 8 centers administration of immunosuppressive treatment as well, even in the absence of histological data. In drug-related nephropathies, RB was considered indicated to confirm the farhypothesis of immunoallergic interstitial nephropathy either if the responsible drug was not among the traditional ones known to induce tubulo-interstitial renal disease or if the pharmacological hypothesis seemed no longer sufficient to justify the renal presentation. All centers but one were against performing RB in case of atheroembolic disease. Three centers performed RB in the intensive care unit. As regards RB in patients undergoing treatment with anticoagulants, aspirin was discontinued 5-14 days before the procedure (mean 8 days) and given again 7-15 days afterwards (mean 11.4 days). Ten centers replaced the anticoagulants with low-dose heparin, which was discontinued the day before the procedure; 11 centers asked advice from cardiologists. RB was repeated in 113 cases after a delay of 1 month to 8 years from the first RB. Our analysis shows uniformity in the approach to RB in this Italian region, with some differences compared with the literature: particular attention was paid to severely critical patients, elderly patients, and patients treated with anticoagulant drugs.

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.

The characteristics of patients hospitalized in nephrology wards in Italy have changed in recent years due to the aging Italian population and the increased immigration. We analyzed the demographic and clinical characteristics of patients hospitalized in our nephrology ward (17 beds) from 15 November 2008 to 15 November 2009. In this period there were 507 hospitalizations including 448 patients. The mean age was 64.4+/-18 years (range 16-96 years). Foreigners accounted for 10% of the total; their mean age was significantly lower than that of Italian patients (38.2+/-13.4 vs 67.4+/-15.9 years, p0.01). 36.3% of patients were on dialysis, 10% were transplant recipients: the reasons for admission in these cases were internal medicine related; 18.15% were hospitalized because of emergency unit crowding without indications for admission to a nephrology ward. Hospitalization lasted a mean of 13+/-13 days. The most frequent diagnosis at discharge was acute renal failure (ARF) (28.9%) (prerenal 42.1%, obstructive 12.2%, drug induced 6.8%, other causes of ARF 38.7%). Patients with ARF were older than patients with other kidney conditions (67.05+/-16.98 vs 56.03+/-18.65 years, p0.01). ARF resolved or improved in 86 patients (63.7%). Other diagnoses were cardiovascular disease 25.1%, glomerular disease 18.7%, acute pyelonephritis 10.6%, other 16.7%. Foreign patients presented infectionrelated diseases more often than Italian patients (39.2% vs 20.4%, p=0.02). 392 patients were discharged to their homes, 40 (7.9%) found a place in a long-term care facility or home for the elderly, 25 (4.9%) in other hospital units, and 50 patients died (9.8%). In conclusion, patients hospitalized in nephrology wards in 2009 were mostly elderly with a high frequency of cardiovascular disease and diabetes. The most frequent diagnosis was prerenal ARF. These data suggest the necessity of improving the prevention of this type of kidney disease. Moreover, the length of hospitalization, which is increasing because of difficult clinical and social situations, could be shortened if more nursing homes, convalescent homes and homes for the elderly were available in Italy.

Vesicoureteral reflux (VUR) may be congenital or acquired. The most frequent form of congenital VUR is primary VUR. Its prevalence in adults is not exactly known, but it is higher in women, whose greater propensity for urinary tract infections increases the likelihood of an instrumental examination leading to the diagnosis of less severe cases. In men, even severe VUR may go undiagnosed for a long time. Primary VUR is due to a defect in the valve mechanism of the ureterovesical junction. In physiological conditions, the terminal ureter enters the bladder wall obliquely and bladder contraction leads to compression of this intravesical portion. Abnormal length of the intravesical portion of the ureter due to a genetic mutation (whose location is yet to be established) leads to VUR. In its less severe forms VUR may be asymptomatic, but in 50-70% of cases it manifests with recurrent cystitis or pyelonephritis. The manifestations leading to a diagnosis of VUR in adults, besides urinary tract infections, are proteinuria, renal failure and hypertension. The gold-standard diagnostic examination is a micturating cystourethrogram. Reflux nephropathy develops as a result of a pathogenetic mechanism unrelated to high cavity pressure or urinary tract infections but due to reduced formation of the normal renal parenchyma (hypoplasia or dysplasia). Abnormal renal parenchyma development is attributable to the same genes that control the development of the ureters and ureterovesical junction. VUR is considered only a marker of this abnormal development, playing no role in scar formation. There is no conclusive evidence regarding the indications for VUR correction. However, the risk that VUR leads to recurrent pyelonephritis and reflux nephropathy must be kept in mind. VUR certainly has to be corrected in women who contemplate pregnancy.

The treatment of membranous glomerulonephritis (MGN) is controversial, especially in cases of no response to first-line treatment or multiple relapses. The Clinical Nephrology Group of Piedmont carried out a multicenter analysis of the treatment of patients affected by MGN in 15 nephrology units in Piedmont. The first treatment is usually started after a waiting period of 3-6 months in case of proteinuria in the nephrotic range but normal or slightly impaired renal function. A history of cancer, the presence of infectious disease, and secondary forms of MGN are criteria for exclusion from treatment. As first-line treatment, Piedmont nephrologists prescribe corticosteroids alternated with immunosuppressive drugs, generally preferring cyclophosphamide to chlorambucil. Only one nephrology unit uses cyclosporin A (CyA) as the first choice. In case of no response to treatment, a second therapeutic approach is undertaken after 2-12 months. Second-line treatment consists of CyA if immunosuppressive drugs were given before, and corticosteroids/ immunosuppressive drugs if CyA was the first treatment. A further choice may be ACTH or rituximab. In case of multiple relapses the treatment options are the same but previous immunosuppressive treatment, patient age, and the duration of kidney disease with a greater probability of renal failure and progression towards sclerosis require careful attention. Concern has been expressed regarding the potentially severe side effects of ACTH including myopathy, cataract and diabetes. In conclusion, the applied therapeutic approaches in Piedmont reflect the difficulty reported in the literature in identifying simple recommendations. ACTH and rituximab are increasingly preferred for the treatment of MGN and there is a need for prospective studies to determine the best protocol for rituximab and the safety profile of ACTH.

The nephrotoxicity of some cancer drugs is well known. Given the rapid development of cancer research, careful assessment of patients treated with new drugs, which may have new toxicity profiles, is mandatory. The nephrotoxicity of cisplatin is likely due to inhibition of autophagy priming, while that of methotrexate is related to direct tubular toxicity and intratubular precipitation. Both can be prevented by adequate hydration. The mechanism of radiation nephropathy development is unclear, but chronic oxidative stress and inflammation seem to play a key role. Mesangiolysis is a characteristic feature, followed by vascular alterations, atrophy, fibrosis, and necrosis. Inhibitors of vascular endothelial growth factor (VEGF), such as bevacizumab, sunitinib, and sorafenib, interfere with angiogenesis. Bevacizumab is a humanized monoclonal antibody which binds to circulating VEGF. Sunitinib and sorafenib are small molecules inhibiting tyrosine kinase of the intracellular domain of the VEGF receptor. Treatment with anti-VEGF drugs is frequently complicated by proteinuria, acute renal failure, and hypertension. The most frequent histological lesion is thrombotic microangiopathy. Inhibitors of the BCR-Abl tyrosine kinase domain on the Philadelphia chromosome (imatinib, nilotinib and dasatinib) may cause acute renal failure.

Isolated asymptomatic hematuria is frequently encountered in clinical practice but there are no established recommendations for its evaluation and management. There is controversy regarding which tests are necessary and whether renal biopsy is indicated. In the pediatric population, renal biopsy should be considered if there is evidence of progressive renal disease or when parents are worried about their child's diagnosis or prognosis. In adults, examinations for isolated microhematuria should include exclusion of pharmacological causes, journeys to endemic areas for S. haematobium or tuberculosis, sickle-cell disease, endometriosis and, in patients older than 40 years, kidney, ureteral or bladder cancer. Examination of urinary sediment may help in identifying the origin of microhematuria. If it is decided to perform a renal biopsy, the patient should be carefully informed of the possible complications of renal biopsy, including the possibility of finding normal renal tissue.

Conclusion. This short course of therapy with prednis- one and cyclophosphamide has been effective in a Background. IgA nephropathy is associated with a wide spectrum of possible lesions. Therefore, different subset of IgA nephropathy patients with florid glomer- ular changes and major urinary abnormalities, turning responses to anti-inflammatory or immunosuppressive therapies should be expected with acute inflammatory off phlogistic activity and preventing subsequent progression toward renal failure. changes, which are predominantly reversible, and with prevalently sclerotic lesions. Methods. The effects of a combined schedule of pred- nephropathy; renal disease progression nisone and cyclophosphamide was analysed in the specific subset of IgA nephropathy patients with acute inflammatory histologic changes associated with haem- aturia and proteinuria. Two groups of patients, with Introduction similar histologic lesions and clinical presentation, were considered. The first group (12 patients) was treated Due to its wide variability in clinical presentation and within 1 week after renal biopsy; starting with three histologic changes, IgA nephropathy has been defined pulses of methylprednisolone (1 g) followed by oral as a 'microcosmos of glomerular lesions' (1). Some prednisone (0.8 mg/kg body weight for 2 weeks, histologic lesions are irreversible and progress towards 0.6 mg/kg for another 2 weeks, 0.4 mg/kg for an obliteration of glomerular capillaries; others are additional 4 weeks, then slowly tapered by 5 mg each acute inflammatory processes, potentially susceptible month until discontinuation) and 1.5 mg/kg cyclophos- to reversal by means of antiphlogistic and immuno- phamide for 2 months. A second sample of eight suppressive therapies (1,2). Therefore, it is difficult to untreated patients served as a control group. Treated identify truly homogeneous subsets of patients for and untreated patients had diffuse mesangial prolifera- treatment trials (especially if the entry criteria are tion with florid crescents (8-60% in treated and based on a single variable such as urinary protein 10-40% in untreated patients) with mild degree of excretion). This possibly explains the conflicting results glomerular sclerosis and interstitial changes. Basal of reports on corticosteroids and cytotoxic drugs in creatinine (167 mmol/l, range 79-371 vs132 mmol/l, these patients (3). range 79-256) and proteinuria (3.0 g/24 h, 1.0-4.9 vs In order to assess the long-term effects of a combina- 3.3 g/24 h, 1.0-13.7) were not statistically different tion of prednisone and cyclophosphamide on renal between treated and untreated patients respectively. function in a subset of IgA nephropathy patients with Nine treated and six untreated patients were hypertens- acute phlogistic histologic changes associated with ive. Blood pressure treatment did not include ACE- haematuria and proteinuria, two samples of patients inhibitors. with similar histologic lesions and clinical presentation

Renal transplantation in patients who have undergone coronary revascularization remains a matter of concern, few experiences have been reported in literature. From January 1997 to March 2003, 23 previously revascularized patients underwent renal transplants from cadaveric donors. We analyzed patient survival and cardiac events in this group of patients (group A) versus a similar population of 38 revascularized patients who were still on dialysis (group B) on the active waiting list (awl). After a similar follow-up (29.30 +/- 21.34 months versus 32.98 +/- 31.33 months; P = .56), survival was 100% for renal transplant patients and 94.74% for dialysis patients, two of whom (5.26%) died from acute myocardial infarction and four (10.52%) were excluded from the waiting list because of cardiac problems. The event-person ratio was 0.51 for group A patients (75% of events clustered within the first 6 months) and 0.71 for group B. The need for therapy with nitrates decreased from 11/23 (47.8%) to 6/23 (26%) after transplant. The ejection fraction remained stable (53.82% +/- 10.4% vs pre-Tx value of 54.8% +/- 9.4%). Renal survival was 100% (sCr = 1.4 +/- 0.4 mg/dL). Although no statistical significance has emerged, there was a general trend in favor of transplanted patients. On the basis of this experience we believe that coronary revascularization per se should no longer be a matter of concern for renal transplantation, which could be superior to dialysis for this type of patient.

Smoking as a risk factor for end-stage renal failure in men with primary renal disease.BackgroundIt is not known whether smoking increases the risk of end-stage renal failure (ESRF) in patients with primary renal disease.MethodsWe performed a retrospective multicenter case-control study including 582 patients from nine centers in Germany, Italy and Austria. The diseases investigated were IgA glomerulonephritis (IgA-GN) as a model of inflammatory renal disease and autosomal dominant polycystic kidney disease (ADPKD) as a model of non-inflammatory renal disease. Cases were patients who had progressed to ESRF and controls were patients who were not in ESRF, that is, whose serum-creatinine failed to progress to >3mg/dl during the observation period and who did not require renal replacement therapy. Matching for renal disease (IgA-GN, ADPKD), gender, age at renal death and region of residence resulted in 102 individually matched pairs (IgA-GN N = 54, ADPKD N = 48). Multiple conditional logistic regression was used to estimate adjusted odds ratios for independent tobacco effects.ResultsIn men (matched pairs: IgA-GN N = 44, ADPKD N = 28), a significant dose-dependent increase of the risk to progress to ESRF was found (non-adjusted). The baseline risk was defined as 15 PY = 5.8 (2.0 to 17), P = 0.001. Systolic blood pressure, ACE inhibitor treatment and age at diagnosis emerged as potential confounders. After adjustment, the risk for ESRF in men with >5 PY was highly increased for patients without ACE inhibitor treatment [10.1 (2.3 to 45), P = 0.002] but not with ACE inhibitor treatment [1.4 (0.3 to 7.1), P = 0.65].ConclusionSmoking increases the risk of ESRF in men with inflammatory and non-inflammatory renal disease.

UNLABELLED PURPOSE AND DESIGN OF STUDY: In this retrospective analysis the effects of combined treatment with steroid pulses, cyclophosphamide and plasma exchange on six crescentic IgA glomerulonephritis (IgAGN) patients, selected on a histological basis, were examined. The histological criteria included involvement of more than 40% of glomeruli by cellular crescents. The effects of this treatment were compared to those observed in three untreated crescentic IgAGN patients and 12 treated patients who had extracapillary glomerulonephritis of different origins, i.e. ANCA-associated systemic or renal-limited vasculitis. All patients, except the three crescentic untreated IgAGN patients, received the same 2-month treatment according to a standardized protocol: steroid boli 15 mg/kg methylprednisolone for 3 consecutive days by intravenous infusion, followed by prednisone per os (1 mg/kg/day for 4 weeks, 0.75 mg/kg/day for 4 more weeks), cyclophosphamide per os 2.5 mg/kg/day for 8 weeks, and plasma exchange. RESULTS After this 2-month course of therapy, substantial clinical improvement was observed in both IgAGN and vasculitis patients. However, a second biopsy revealed that florid crescents persisted in IgAGN patients and, unlike the vasculitis group, during the long-term the initial clinical amelioration disappeared in one-half of the treated IgAGN cases. Nevertheless, even in the progressive cases, intensive treatment seemed to substantially delay the onset of dialysis. CONCLUSIONS Despite some clinical benefits of therapy, short-term reversal of active crescents appears less likely to occur in crescentic IgAGN than in vasculitis-associated crescentic GN. Intensive treatment seems sufficient to arrest, but inadequate to reverse, phlogistic lesions in IgAGN before development of chronic changes.

Two hundred and one patients had biopsies of their native kidneys with ultrasound-guided needle technique. They were evaluated on the second post-biopsy day with colour-coded Doppler sonography. Ten patients out of these 201 were found to have an arteriovenous fistula, which remained asymptomatic for the whole follow-up period (follow-ups ranged from 2 to 31 months). Four of these 10 patients developed a perirenal haematoma as well and five macroscopic haematuria. Our study shows that the systematic use of colour-coded Doppler sonography after renal biopsy facilitates diagnosis of arteriovenous renal fistula.