Predictors of increase in chronicity index and of kidney function impairment at repeat biopsy in lupus nephritis.

OBJECTIVES: Based on available data, the histological predictors of long-term outcome of lupus nephritis (LN) are not clearly defined. Aims of this retrospective study were: (i) to evaluate the change of chronicity index from the first to second kidney biopsy and to find the predictors of chronicity index increase and (ii) to detect the clinical/histological features at first and at second kidney biopsy associated with long-term kidney function impairment. METHODS: Among 203 biopsy proven LN subjects, 61 repeated kidney biopsy 49 months after the first biopsy. The reasons for repeated biopsy were: nephritic flares in 25 (41%), proteinuric flares in 21 (36%) of patients and protocol biopsy in 14 (23%) of cases. RESULTS: During 23-year follow-up, 25 patients presented a decrease in glomerular filtration rate (eGFR) ≥30%. At repeat biopsy, chronicity index increased in 44 participants (72%) and did not increase in 17 (28%). Nephritic syndrome and serum creatinine >1.6 mg/dL at presentation correlated with chronicity index increase (p=0.031, 0.027, respectively), cyclophosphamide therapy tended to protect against chronicity index increase (p=0.059). Kidney flares occurred in 53.6% of patients with vs 23.5% of those without chronicity index increase (p=0.035). Chronicity index increases of 3.5 points in patients with kidney flares vs 2 in those without flares (p=0.001). At second, but not at first kidney biopsy, two different models predicted eGFR decrease at multivariate analysis. The first included activity index >3 (OR: 3.230; p=0.013) and chronicity index >4 (OR: 2.905; p=0.010), and the second model included moderate/severe cellular/fibrocellular crescents (OR: 4.207; p=0.010) and interstitial fibrosis (OR: 2.525; p=0.025). CONCLUSION: At second biopsy, chronicity index increased in 3/4 of participants. Its increase was predicted by kidney dysfunction at presentation and occurrence of LN flares. Kidney function impairment was predicted by both activity and chronicity index and by some of their components at repeated biopsy, but not at first biopsy.

Beyond ISN/RPS Lupus Nephritis Classification: Adding Chronicity Index to Clinical Variables Predicts Kidney Survival.

Background: A renewed interest for activity and chronicity indices as predictors of lupus nephritis (LN) outcome has emerged. Revised National Institutes of Health activity and chronicity indices have been proposed to classify LN lesions, but they should be validated by future studies. The aims of this study were (1) to detect the histologic features associated with the development of kidney function impairment (KFI), and (2) to identify the best clinical-histologic model to predict KFI at time of kidney biopsy. Methods: Patients with LN who had more than ten glomeruli per kidney biopsy specimen were admitted to the study. Univariate and multivariate logistic regression and Cox proportional hazards models were used to investigate whether activity and chronicity indices could predict KFI development. Results: Among 203 participants with LN followed for 14 years, correlations were found between the activity index, and its components, and clinical-laboratory signs of active LN at baseline. The chronicity index was correlated with serum creatinine. Thus, serum creatinine was significantly and directly correlated with both activity and chronicity indices. In the multivariate analysis, glomerulosclerosis (OR, 3.05; 95% CI, 1.17 to 7.91; P=0.02) and fibrous crescents (OR, 6.84; 95% CI, 3.22 to 14.52; P<0.001) associated with either moderate/severe tubular atrophy (OR, 3.17; 95% CI, 1.04 to 9.64; P=0.04), or with interstitial fibrosis (OR, 2.36; 95% CI, 1.05 to 5.32; P=0.04), predicted KFI. Considering both clinical and histologic features, serum creatinine (OR, 1.68; 95% CI, 1.31 to 2.15; P<0.001), arterial hypertension (OR, 4.64; 95% CI, 1.90 to 11.32; P<0.001), glomerulosclerosis (OR, 2.12; 95% CI, 1.00 to 4.50; P=0.05), and fibrous crescents (OR, 5.18; 95% CI, 2.43 to 11.04; P<0.001) independently predicted KFI. Older age (P<0.001) and longer delay between clinical onset of LN and kidney biopsy (P<0.001) were significantly correlated with baseline chronicity index. Conclusions: The chronicity index and its components, but not the activity index, were significantly associated with an impairment of kidney function. The Cox model showed that serum creatinine, arterial hypertension, chronic glomerular lesions, and delay in kidney biopsy predicted KFI. These data reinforce the importance of timely kidney biopsy in LN.

[The origins of the Renal Immunopathology Group of the Italian Society of Nephrology].

This article describes the birth and development of the Renal Immunopathology Group of the Italian Society of Nephrology. It collects the stories of nephrologists and pathologists who, since the early Seventies up to the first decade of this century, devoted their professional lives to the study of renal pathology with a strong personal involvement, characterized by enthusiasm, commitment, ability, strong spirit of cooperation, and friendship. All this enabled the Group to: propose the criteria for a standardized histological and immuno-histological examination of renal biopsies and reporting; produce several multicenter studies, whose results were also published in important international journals; to set up a national registry of renal biopsies; to organize a number of courses, some of which were associated with the publication of monographs, on various renal diseases. This article also traces the history of renal pathology in Italy from the second half of the Sixties - when young Italian nephrologists and pathologists from different institutions moved to French laboratories to learn new techniques to apply to renal biopsies - up to the present days. It also shows us how Italian renal pathology has been an essential tool for the development of the nephrological clinical practice and the advancement of scientific research.

Antiviral therapy of symptomatic HCV-mixed cryoglobulinemia after liver transplant: case report and literature review.

Hepatitis C virus (HCV) infection may be associated with extra-hepatic illness including mixed cryoglobulinemia (MC). Consistent evidence exists on HCV-MC in the non-transplantation setting but information on HCV-related cryoglobulinemia after solid organ transplantation is limited, particularly after liver transplantation (LT). We report on a 48-year-old man who developed HCV-associated cryoglobulinemic vasculitis with recurrent hepatitis after liver transplant. One year after transplant for HCV-positive cirrhosis, he presented severe cutaneous manifestations, and biopsy-proven cryoglobulinemic membrano-proliferative glomerulonephritis (MPGN). HCV RNA clearance occurred within a few weeks of antiviral therapy; sustained viral response (SVR) was obtained by one year of anti-HCV combination therapy (eight months of pegylated IFN/ribavirin and four months of standard IFN/ribavirin). SVR was linked to complete remission of skin, liver, and kidney abnormalities. Tolerance to the pegylated IFN/ribavirin regimen was not excellent due to the occurrence of lobar pneumonia with anemia; thus, peg-IFN was replaced by recombinant IFN, with a favorable outcome. Clinical and viral remission persisted over a 48-month follow-up. HCV-associated mixed cryoglobulinemia flareups following LT were successfully managed with combined antiviral therapy. HCV-related MC is uncommon in developed countries and this clearly hampers randomized controlled clinical trials aimed at evaluating the efficacy and safety of anti-HCV therapy after solid organ transplantation or in the non-transplantation setting.

The long-term outcome of renal transplantation of IgA nephropathy and the impact of recurrence on graft survival.

BACKGROUND: Few data are available on allograft survival at 15 years, the impact and the predictors of recurrence of the original disease in renal transplanted patients with IgA nephropathy (IgAN). METHODS: In this retrospective study, we compared the long-term outcome of renal transplant in 190 patients with IgAN with that of 380 non-diabetic controls and evaluated the impact of recurrence of IgAN on the graft outcome. RESULTS: At 15 years, the patient survival was 88.3% in IgAN patients and 82.6% in controls (P = 0.12), while the death-censored graft survival was 62.6 and 72.4%, respectively (P = 0.038). IgAN had a higher cumulative incidence of graft failures in comparison with controls even considering death as a competing risk (P = 0.025). At multivariate analysis, IgAN [relative risk (RR) = 1.468, P = 0.026], delayed graft function recovery (RR = 2.394, P = 0.000) and acute rejection (RR = 2.51, P = 0.000) were predictive of graft loss. IgAN recurred in 42 grafts (22.1%), of them, 12 were lost for recurrence and in another 6 recurrence was considered a concomitant cause of graft loss. The 15-year death censored graft survival was 68.3% in non-recurrent and 51.2% in recurrent patients (P = 0.069). Pure graft survival of non-recurrent IgAN patients was similar to that of controls (P = 0.406). At Cox analysis, the recurrence of IgAN significantly reduced from 1981 to 2010 (P = 0.0065, RR = 0.936). CONCLUSIONS: IgAN emerged as an independent predictor of worse graft outcome in the long-term. Recurrence of IgAN seems to progressively reduce in transplants performed from 1981 to 2010.

Outcome of fibrillary glomerulonephritis.

QUESTIONS UNDER STUDY: We assessed the long-term follow up of all the patients with fibrillary glomerulonephritis diagnosed since 1992 at our centre of reference for renal pathology in Basel. METHODS: We performed a retrospective surveillance study with mail questionnaire based follow-up of all patients with the diagnosis of fibrillary glomerulonephritis found in the database of the department of renal pathology in Basel from 1992 to 2007. The outcome was assessed in terms of endstage renal disease (ESRD), death, reduction of proteinuria and improvement of estimated glomerular filtration rate (eGFR). RESULTS: We obtained sufficient follow up data from 16 out of 20 identified patients. The mean follow up time was 35 months (1-115.1). Six patients died (37.5%), three without having ESRD. Six patients (37.5%) reached ESRD, five of them went on hemodialysis. Thirteen patients (81.3%) received an immunosuppressive therapy with steroids, five of them in combination with cyclophosphamide. The group without immunosuppressive therapy was too small to compare the two groups. In relation to the histological pattern membranous glomerulonephritis (MGN) had a better outcome as compared to the other histological patterns. CONCLUSIONS: FGN is a heterogeneous disease associated with significant risk of ESRD and mortality. The histological type of the glomerulonephritis may influence the course of the disease.

HBV-related liver disease in renal insufficiency: successful antiviral therapy with entecavir.

Hepatitis B virus (HBV) infection persists among patients with renal insufficiency in the industrialized world. A variety of therapeutic options are now available for the treatment of chronic hepatitis B infection, including potent new nucleos(t)ide analogs, along with standard and pegylated interferon. We report on a patient with aggressive hepatitis B and renal insufficiency who was successfully treated with nucleoside analogs (mostly entecavir monotherapy) for two years. He received intense immunosuppression for severe myopathy of lower limbs, probably related to vasculitis. HBV DNA (at the beginning, > 1 x 10(8) IU/mL) was no longer detectable in serum after a few months of antiviral therapy, while HBeAg and HBsAg seroconversion occurred with ALT normalization. Clinical signs of vasculitis disappeared. Five months after discontinuation of entecavir therapy, he remained HBsAg negative with detectable anti-HBs antibody in serum. We conclude that nucleos(t)ide analogs can offer excellent response in selected patients with renal insufficiency and hepatitis B-related liver disease. Prospective, controlled clinical trials are needed to confirm these encouraging results.

Membranoproliferative glomerulonephritis type I in renal transplantation patients: a single-center study of a cohort of 68 renal transplants followed up for 11 years.

BACKGROUND: To evaluate the long-term outcome of renal transplant patients with membranoproliferative glomerulonephritis (MPGN) type I and the impact of recurrence. METHODS: The outcomes of 68 renal transplants performed between 1976 and 2009 in 63 patients with MPGN were compared with those of 136 controls matched for time of transplantation, sex, age, and source of donors. RESULTS: The mean posttransplant follow-up was 131.3±83.8 months for patients with MPGN and 139.21±88.7 months for controls. At 15 years, patient survival rates were 76.2% in patients with MPGN and 78.8% in controls (P=ns), whereas pure graft survival rates were 68% in MPGN and 67.9% in controls (P=ns). MPGN recurred in 16 patients (23.5%) 44±30.3 months after transplant (range, 3.5-105 months). Of recurrent grafts, nine were lost for recurrence within 116.5±51.36 months, three patients died with functioning kidney, the other 4 grafts are functioning 156.7±47.5 months after transplantation. Graft survival at 15 years was 73.5% in nonrecurrent and 40.4% in recurrent patients (P=0.02). Patients with recurrence were younger at diagnosis of MPGN (17.64±5.02 years vs. 22.9±9.6 years; P=0.037) and had low C3 more frequently than nonrecurrent patients (75% vs. 28.8%; P=0.01). Proteinuria was higher in recurrent patients who lost the graft in comparison with those with functioning graft (7.14±4.05 vs. 2.86±1.95; P=0.02). CONCLUSIONS: The long-term patient and graft survival were similar in patients with MPGN and in controls. Recurrence occurred in one-fourth of patients and caused graft loss in 56%. Younger age at diagnosis of MPGN and low C3 during transplantation seems to be predictive of recurrence.

Carotid plaques in patients with long-term lupus nephritis.

OBJECTIVES: To evaluate the prevalence of carotid plaques in patients with long-term lupus nephritis (LN). METHODS: Intima-media thickness (IMT) and carotid plaques were evaluated with ultrasound in 75 patients after a follow-up of LN of 158+/-106 months and in 75 sex -and age-matched controls. Traditional and non-traditional atherosclerotic risks factors were also tested. RESULTS: IMT was not different between LN patients and controls, but 18% of LN patients had carotid plaques in comparison to 2.6% of controls (p=0.004). The LN patients more frequently had hypertension (p=0.0001), hypercholesterolemia (p=0.0001), were overweight (p=0.009), in menopause (p=0.01) than controls. More frequently, LN patients with carotid plaques had renal insufficiency (p=0.03), longer duration of lupus (p=0.05), anti-phospholipid antibodies (p=0.018), high C-reactive protein (p=0.03), high reactive oxygen species (p=0.001) than those without plaques. Patients with plaques were older (p=0.000001), in menopause (p=0.000001) and more frequently had cardio-vascular accidents during observation (p=0.02). The time of exposure to pathological values of systolic and diastolic blood pressure was longer (p=0.000001) and the percentage of pathological values of these variables during the follow-up was higher (p=0.000001) in patients with carotid plaques. At multivariate analysis, older age (p=0.0025), longer time of exposure to pathological values of blood pressure (p=0.015) and of cholesterol (p=0.04) were independent predictors of carotid plaques. CONCLUSIONS: Carotid plaques were more frequently found in LN patients than in controls. Although inflammatory markers and lupus related factors may contribute to the development of atherosclerosis, only traditional risk factors such as age, hypertension and hypercholesterolemia were the independent predictors.

Long-term outcome of renal transplantation in patients with idiopathic membranous glomerulonephritis (MN).

BACKGROUND: Little information is available about the long-term outcome of renal transplanted patients with idiopathic membranous nephropathy (MN). METHODS: The outcomes of 35 first renal transplants performed between 1975 and 2008 in patients with MN were compared with those of 70 controls transplanted in the same period and matched for sex, age and source of donors. RESULTS: The mean post-transplant follow-up was 117 ± 86 months for MN patients and 123 ± 83 months for controls. At 15 years, patient survival was 96% in patients with MN and 88% in the controls (P = ns), while graft survival rates were respectively 40% and 69% (P = 0.06). MN recurred in 12 patients (34%), namely in 4/8 (50%) patients who received the kidney from related living donors and in 8/27 (29.6%) who received the kidney from a deceased donor. Recurrence led to graft failure in six patients, all deceased donor kidney recipients, within 54 ± 33 months. The other six grafts are functioning 134 ± 73 months after transplantation. Patients with recurrence were more frequently females (42% vs 4.3%, P = 0.02). The recurrence occurred earlier (4.8 ± 3.0 vs 45.6 ± 46.9 months, P = 0.05), and there was a trend to develop a higher proteinuria (7.1 ± 5.5 vs 3.67 ± 2.6 g/24 h, P = 0.1) in grafts eventually lost because of recurrence. CONCLUSIONS: The long-term patient survival was similar in renal transplant recipients with MN and in controls. The graft survival was lower in MN patients than in controls, although the difference was at borderline significance. Recurrence occurred in one-third of the patients and caused graft loss in half of them.

Rituximab monotherapy for remission induction of proliferative lupus nephritis flares: description of 3 cases.

BACKGROUND: The efficacy and safety of rituximab when not associated with other immunosuppressive therapy in induction of remission of proliferative lupus nephritis (PLN) has not until now been proven. METHODS: We report on 3 patients with PLN (class IV), 1 with a nephritic flare and 2 with a proteinuric flare (all with nephrotic syndrome (NS)) treated with 3 intravenous methylprednisolone pulses for 3 consecutive days and with rituximab at day 3 and day 18 associated with oral prednisone. At the beginning of the fourth month of therapy, mycophenolate mofetil was combined with prednisone. RESULTS: Three months after the beginning of therapy, renal function improved in the patient with the nephritic flare, and proteinuria fell to within the non-nephrotic range in all 3 patients. At the end of a follow-up of 24 months, the patient with the nephritic flare had normal renal function (serum creatinine from 1.7 to 1 mg/dL) and mild proteinuria (from 6 to 0.7 g/24 hours). The second patient was in complete remission (proteinuria from 5 to 0.127 g/24 hours) 27 months after the beginning of therapy. In the last patient, followed for 10 months, mild proteinuria persisted (from 6.6 to 0.7 g/24 hours). The therapy was well tolerated by all patients. No adverse effects occurred during the follow-up. CONCLUSION: Although our results must be confirmed by larger prospective studies, rituximab associated with methylprednisolone pulses without any other concomitant immunosuppressive drug seems to be effective and safe for induction therapy of severe flares of PLN.

Severe reversible acute renal failure in idiopathic nephrotic syndrome.

BACKGROUND: Only few cases of acute renal failure (ARF) requiring dialysis have been reported in patients with idiopathic nephrotic syndrome (NS). This study aims to better define the clinical outcome and treatment of this condition. METHODS: A pilot enquiry regarding the occurrence of ARF requiring dialysis in patients with NS and biopsy proven minimal changes (MC) or focal segmental glomerulosclerosis (FSGS) was conducted among 5 nephrology centers. RESULTS: From 1996-2006, 6 patients with idiopathic NS (4 MC, 2 FSGS) developed ARF requiring dialysis early after onset of NS. At presentation all but 1 patient had elevated blood pressure. Patients were treated with dialysis from 7-40 days. All achieved complete or partial remission after 4-8 weeks of steroids. Recovery of renal function paralleled with the reduction of proteinuria. At renal biopsy proximal tubules showed a large amount of protein droplets, flattening of epithelial cells, and focal detachment of cells from the basal membrane. After a follow-up of 24-60 months, 5 patients had a relapse. Of these 4 were responsive to steroids, while one progressed to dialysis after an episode of hemolytic uremic syndrome related to cyclosporine treatment. ARF did not recur. CONCLUSION: ARF requiring dialysis is a rare and unexpected complication of idiopathic NS occurring in most cases early after presentation. These patients are sensitive to steroids that should be administered as promptly as possible in view of the potential noxious effect of protein overload on proximal tubular cells.

Long-term outcome of renal transplantation in adults with focal segmental glomerulosclerosis.

SUMMARY: Little information is available about the long-term results of kidney transplantation in adults with focal segmental glomerulosclerosis (FSGS). The outcomes of 52 renal transplants performed between 1988 and 2008 in 47 adults with FSGS were compared with those of 104 matched controls (median follow-up 93.4 vs. 109.4 months respectively). At 15 years, patient survival was 100% and graft survival 56% in FSGS patients vs. 88.3% and 64% respectively in controls (P = NS). FSGS recurred in 12 out of 52 grafts (23%) and led to graft failure in seven within 10 months (median). In the other five cases, proteinuria remitted and grafts are functioning 106 months (median) after transplantation. A second recurrence developed in five out of eight re-transplanted patients (62.5%) who lost their first graft because of recurrence; only one graft was lost. Patients with recurrence were more frequently male subjects (83% vs. 40%, P = 0.02), younger at diagnosis of FSGS (16.3 +/- 6.8 vs. 24.1 +/- 11.5 years, P = 0.03) and of younger age at transplantation (28.4 +/- 7.8 vs. 35.8 +/- 12.2 years, P = 0.05). Treatment with plasmapheresis plus ACE inhibitors achieved either complete or partial remission in 80% of the cases. Long-term patient and renal allograft survivals of adults with FSGS were comparable to those of controls. Recurrence was more frequent in young patients and in patients who lost a previous graft from recurrence. Graft loss resulting from a second recurrence is lower than expected.

Renal transplantation in adults with Henoch-Schonlein purpura: long-term outcome.

BACKGROUND: Little information is available about the long-term outcome of renal transplantation in adults with Henoch-Schonlein purpura (HSP). METHODS: We compared the outcomes of 17 patients with HSP who received 19 renal transplants with those of 38 controls matched for time of transplantation, age, gender and source of donor. The mean post-transplant follow-up was 109 +/- 99 months for HSP patients and 110 +/- 78 months for controls. RESULTS: The actuarial 15-year patient survival was 80% in HSP patients and 82% in controls, and the death-censored graft survival was 64% in HSP patients and in controls. The risks of acute rejection, chronic graft dysfunction, arterial hypertension and infection were not different between the two groups. In eight grafts (42%) recurrence of HSP nephritis was found (0.05/patient/year). In spite of therapy, one patient died and four eventually restarted dialysis respectively 10, 32, 35 and 143 months after renal transplant. Seventy-one percent of grafts transplanted in patients with necrotizing/crescentic glomerulonephritis of the native kidney had HSP recurrence in comparison to 12% of recurrences in patients with mesangial nephritis (P = 0.05) CONCLUSIONS: Long-term patient and allograft survival of HSP patients was good. However, 42% of HSP patients, particularly those with necrotizing/crescentic glomerulonephritis of the native kidneys, developed a recurrence of HSP nephritis that eventually caused the loss of the graft function in half of them.

The long-term outcome of 93 patients with proliferative lupus nephritis.

BACKGROUND: Few data are available about the very long-term outcome of patients with proliferative lupus nephritis. METHODS: Ninety-three Italian patients with biopsy-proven proliferative lupus nephritis (15 with class III, 9 with class III+V, 64 with class IV and 5 with class IV+V) followed for a median follow-up of 15 years in a single renal unit were considered for this observational study. Patients were treated with an induction treatment consisting of high doses of corticosteroids plus immunosuppressive agents in the more severe cases. This treatment was repeated in the event of a renal flare. Then corticosteroids and immunosuppressive agents were reduced to the minimal effective dose for maintenance. RESULTS: Renal survival including death was 97% at 10 years and 82% at 20 years. At the last follow-up visit, 59 patients were in complete renal remission, 18 were in partial renal remission, four patients had chronic renal insufficiency, six had entered end-stage renal disease and six patients had died. At multivariate analysis the lack of achievement of complete renal remission and the occurrence of nephritic flares were significantly correlated both with the risk of doubling plasma creatinine and death or dialysis. Those patients who entered complete renal remission had significantly less probability of developing nephritic flares. CONCLUSION: The long-term prognosis of Caucasian patients with proliferative lupus nephritis may be better than usually thought. Favorable factors for good long-term outcome are the achievement of complete renal remission, the absence of nephritic flares and their complete reversibility after therapy.

Multicenter study on hepatitis C virus-related cryoglobulinemic glomerulonephritis.

BACKGROUND: Mixed cryoglobulinemia is a multisystem disorder associated strongly with hepatitis C virus (HCV) infection. The kidney frequently is involved, and glomerulonephritis represents the key factor affecting prognosis. METHODS: Clinical, serological, immunogenetic, and morphological data were collected retrospectively from medical records of 146 patients with cryoglobulinemic glomerulonephritis who underwent biopsies in 25 Italian centers and 34 cryoglobulinemic controls without renal involvement. RESULTS: Eighty-seven percent of patients were infected with HCV; genotype 1b was more frequent than genotype 2 (55% versus 43%). Diffuse membranoproliferative glomerulonephritis was the most prevalent histological pattern (83%). Type II cryoglobulin (immunoglobulin Mkappa [IgMkappa]/IgG) was detected in 74.4% of cases. The remainder had type III (polyclonal IgM/IgG) cryoglobulins. A multivariate Cox proportional hazard model showed that age, serum creatinine level, and proteinuria at the onset of renal disease were associated independently with risk for developing severe renal failure at follow-up. Overall survival at 10 years was about 80%. Kaplan-Meier survival curves were worsened by a basal creatinine value greater than 1.5 mg/dL (>133 mumol/L), but were unaffected by sex and HCV infection. Cardiovascular disease was the cause of death in more than 60% of patients. CONCLUSION: Data confirm the close association between mixed cryoglobulinemia and HCV infection and between glomerulonephritis and type II cryoglobulin. Survival profiles are better than previously reported in the literature, probably because of improvement in therapeutic regimens. Causes of death reflect this improvement in survival, with an increased prevalence of cardiovascular events compared with infectious complications and hepatic failure, which were predominant in the past.

Thrombotic microangiopathy after kidney transplantation.

Two forms of post-transplant thrombotic microangiopathy (TMA) may be recognized: recurrent TMA and de novo TMA. Recurrent TMA may occur in patients who developed a nondiarrhoeal form of haemolytic uraemic syndrome (HUS) being particularly frequent in patients with autosomal recessive or dominant HUS. The recurrence is almost the rule in patients with mutation in complement factor H gene. Most patients eventually lose the graft. Treatment with plasma infusions or plasmapheresis is often disappointing, but few cases may be rescued. Intravenous immunoglobulins and rituximab have also been successful in anedoctic cases. De novo TMA is rarer. A number of factors including viral infection may be responsible of de novo TMA, but in most cases TMA is triggered by calcineurin inhibitors or mTOR inhibitors. The clinical presentation of de novo TMA may be variable with some patients showing clinical and laboratory features of HUS while others showing only a progressive renal failure. The prognosis is less severe than with recurrent TMA. Complete withdrawal of the offending drug may lead to improvement in many cases. The addition of plasma exchange may result in graft salvage in about 80% of cases.

Long-term outcome of idiopathic retroperitoneal fibrosis treated with surgical and/or medical approaches.

BACKGROUND: Retroperitoneal fibrosis is a severe disease that affects the ureters, causing renal insufficiency in three-quarters of patients. The optimal treatment is far from being established. METHODS: Seventeen patients with idiopathic retroperitoneal fibrosis and ureteral entrapment followed in our unit for at least 1 year were selected for this study. At presentation 13 patients had renal insufficiency. All patients received steroids, associated with ureterolysis in five (group 1), with azathioprine in six (group 2) and with tamoxifen in six (group 3). Four patients of group 2 and five of group 3 received ureteral stenting or nephrostomy. There were no significant differences among the three groups or the clinical and biochemical characteristics at presentation. RESULTS: All patients of groups 1 and 2 entered remission after therapy. One patient from group 3 did not respond to therapy. During a mean follow-up of 56 +/- 41 months, three patients (two from group 1, one from group 2, 18%) had a recurrence of the disease, which fully responded to retreatment in all three cases. At the last observation, all patients were alive; three patients (18%) had renal insufficiency, of them one from group 1 had to start dialysis 6 years after ureterolysis, one patient from group 2 and one from group 3 had serum creatinine of 1.5 mg/dl. Renal survival was 100% at 5 years and 80% at 10 years. CONCLUSIONS: In most patients, each of the three different therapeutic approaches restored renal function and significantly reduced the fibrotic mass in the short-term and maintained stable serum creatinine in the long-term.

Withdrawal of therapy in patients with proliferative lupus nephritis: long-term follow-up.

BACKGROUND: Whether corticosteroid and immunosuppressive therapy may be safely withdrawn in patients with proliferative lupus nephritis is still unclear. METHODS: In 32 patients with biopsy-proven proliferative lupus nephritis previously put into remission, therapy was gradually tapered off. RESULTS: When immunosuppressive therapy was stopped (median: 38 months; 25th-75th percentile: 24-81 months, after biopsy), 24 patients were in complete remission and eight had a median proteinuria of 1.05 g/24 h (25th-75th percentile: 0.91-1.1 g/24 h) with normal renal function. After stopping therapy, patients were followed for a median of 203 months (25th-75th percentile: 116-230 months). Fifteen patients (Group 1) never developed lupus activity. The other 17 patients (Group 2) developed lupus exacerbations in a median of 34 months (25th-75th percentile: 29-52 months) after stopping therapy and were re-treated. The only significant differences between the two groups were the longer median durations of treatment, 57 months (25th-75th percentile: 41.5-113.5 months) vs 30 months (25th-75th percentile: 18-41 months; P<0.009), and remission, 24 months (25th-75th percentile: 18-41) vs 12 months (25th-75th percentile: 7-20 months; P<0.02), before stopping therapy in Group 1 than in Group 2. At last follow-up, 12 patients of Group 1 were in complete remission, two had mild proteinuria and one had died. In Group 2, one patient died, 14 were in complete remission, one had mild proteinuria and in another patient serum creatinine doubled. CONCLUSIONS: Some patients with severe lupus nephritis who enter stable remission can be maintained without any specific treatment for many years. Those patients who have new flares can again go into remission with an appropriate treatment. The longer the treatment and remission before withdrawal, the lower the risk of relapse.

Urinary sediment features in proliferative and non-proliferative glomerular diseases.

BACKGROUND: The studies on urine sediment particles in patients with glomerular diseases (GD) are few and have focused only on single urine particles. In this study, we investigated the prevalence and number of 12 urine sediment particles in two groups of patients, one with proliferative GD, and the other with non-proliferative GD. METHODS: The urine sediment of 100 consecutive patients, with a renal biopsy-proven proliferative or non-proliferative GD and marked cylindruria, were examined a few hours before renal biopsy according to a standardized method. The urine particles investigated were erythrocytes, leukocytes, renal tubular cells, lipids and hyaline, hyaline-granular, granular, waxy, erythrocytic, leukocytic, epithelial and fatty casts. RESULTS: Patients with proliferative GD (n=52) had both a significantly higher prevalence of microscopic hematuria, leukocyturia, tubular epithelial cells, erythrocytic casts, epithelial casts, and significantly higher amounts of erythrocytes,leukocytes, tubular epithelial cells/20 high power field (HPF), erythrocytic and epithelial casts. On the other hand, patients with non-proliferative GD (n=48) had significantly higher numbers of fatty casts. In proliferative GD, leukocyturia was associated with intracapillary and extracapillary proliferation, crescents and fibrinoid necrosis at renal biopsy. At discriminant analysis, the two types of GD could be identified with 80.8% sensitivity and 79.2% specificity. By multiple logistic regression analysis, patients with erythrocytes, leukocytes and erythrocytic casts in the urine had an odds ratio (OR) of 9.91 (95% confidence interval (95% CI): 1.01-97.51), 7.85 (95% CI: 2.77-22.20), and 4.33 (95% CI: 1.41-13.31), respectively, of having proliferative GD. CONCLUSIONS: Our examination of the urine sediment shows that proliferative GD and non-proliferative GD differ in many respects.