A new morphologic index for the evaluation of renal biopsies in lupus nephritis

BACKGROUND: Various morphologic indices for the evaluation of renal biopsies in lupus nephritis have been developed, of which the most successful have been the NIH Activity Index (AI) and Chronicity Index (CI). We wished to develop a biopsy index from standard light and immunofluorescence (IF) material that would correlate yet more closely with clinical and outcome parameters than the current indices, and be applicable to both treated and untreated cases. METHODS: A cohort of 71 patients with lupus nephritis who had initial renal biopsies (Bx1) with systematic second biopsies (Bx2) at six months after induction therapy was studied, with a large number of light microscopic and IF variables evaluated. These were examined statistically to choose the combinations of variables with the highest overall correlations with clinical and outcome parameters. RESULTS: The adopted biopsy index comprised four elements: Glomerular Activity Index (GAI), a modification of the standard AI with the addition of glomerular monocytes and elimination of interstitial inflammation; Tubulointerstitial Activity Index (TIAI), evaluating several tubular epithelial and inflammatory components, including interstitial inflammation, but excluding tubular atrophy; Chronic Lesions Index, a modification of the standard CI, with the addition of glomerular scars; IF Index (IFI), a semiquantitative index of IF staining for six standard antisera for glomerular capillary, mesangial, tubulointerstitial, and vascular elements. The Biopsy Index showed a statistically higher correlation with clinical and outcome parameters than the NIH AI (P = 0.0170), the NIH CI (P = 0.0009), or their combination (P = 0.0444). At Bx1, comparisons between correlation coefficients for the appropriate AI or CI value and for the Biopsy Index, were: anti-DNA antibodies (0.30 vs. 045), serum creatinine (SCr; 0.33 vs. 0.48), proteinuria (0.22 vs. 0.36), hemoglobin (-0.21 vs. -0.45), and final renal function (0.22 vs. 0.40). Spearman rank correlations showed similar superiority for outcome parameters: doubling of SCr (0.1810 vs. 0.3018) and end-stage renal disease (0.0529 vs. 0.1925). The same improvement of correlations was seen at Bx2 for most parameters, particularly doubling of SCr (0.2716 vs. 0.4753). CONCLUSIONS: The Biopsy Index and/or its components show better correlations with clinical and outcome parameters than the standard AI and CI and other similar indices.     

Predictive value of renal pathology in diffuse proliferative lupus glomerulonephritis. Lupus Nephritis Collaborative Study Group

We tested the value of the activity (AI) and chronicity (CI) indices devised by Austin et al as predictors of outcome in lupus patients with diffuse proliferative glomerulonephritis (DPGN). Four renal pathologists independently scored the AI and CI on 84 renal biopsy specimens from patients with lupus DPGN followed for 109 +/- 74 weeks (mean +/- SD), and the mean score was compared to the development of renal failure and to adverse outcome (combined data for renal failure, death and predefined clinical stop points). Receiver operator characteristic curves were derived from a series of 2 x 2 tables in which one variable was renal failure or adverse outcome and the other variable was AI or CI dichotomized by a cut-off point. Over the entire range (0 to 10) of the CI there was no value that separated patients who developed renal failure from those who did not. The ROC curve analysis indicated that the sensitivity and specificity of the CI were too low to allow it to function as a good test. Once patients entering renal failure were identified, the mean CI approached but did not reach a significant difference when compared to the mean CI of those who did not go into renal failure (4.38 +/- 0.42, mean +/- SE vs. 3.19 +/- 0.23, P = 0.0620). The CI did not predict the adverse clinical outcomes. There was no cut-off value of the CI which separated patients who had an adverse outcome from those who did not, and this result was confirmed by ROC analysis.(ABSTRACT TRUNCATED AT 250 WORDS)     

Diffuse proliferative lupus nephritis: identification of specific pathologic features affecting renal outcome

Prerandomization renal biopsy specimens were examined in 102 patients upon entry into prospective therapeutic trials of lupus nephritis in an attempt to identify early predictors of renal failure outcome. All 11 renal failures occurred among the 72 individuals with diffuse proliferative or membranoproliferative glomerulonephritis (DPGN/MPGN); thus, these patients were at modestly, but significantly, increased risk of endstage renal disease compared to those with focal proliferative, membranous, or mesangial glomerulonephritis. Considering the low incidence of endstage renal disease among patients with DPGN/MPGN, we sought to refine the prognostic information obtained from renal morphology by semiquantitative scoring of individual histologic features and by derivation of composite histologic scores specified by Activity (AI) and Chronicity (CI) Indices. Among the 72 patients with DPGN/MPGN, the composite AI was more strongly predictive of renal failure than were the individual active histologic features; cellular crescents and extensive fibrinoid necrosis yielded positive associations, while endocapillary proliferation, leucocytic exudation, and hyaline thrombi in glomeruli and interstitial inflammation by themselves did not emerge as useful prognostic indicators. However, chronicity items (glomerular sclerosis, fibrous crescents, tubular atrophy, and interstitial fibrosis) considered individually, as well as in the composite CI, were highly predictive of renal failure outcome. Particularly striking was the prognostic value of tubular atrophy; all 11 renal failures were among the 43 patients with tubular atrophy on prerandomization renal biopsy. While no single pathologic variable improved outcome predictions among those with tubular atrophy, examination for interactions among variables revealed that glomerular sclerosis and cellular crescents had a synergistic effect which augmented the prognostic information derived from analysis of tubular atrophy alone.(ABSTRACT TRUNCATED AT 250 WORDS)     

Monocytes and glomerulonephritis associated with remote visceral infection

The biopsies of 8 patients with diffuse proliferative glomerulonephritis associated with remote visceral infection (GN-RVI) were evaluated by histochemistry and electron microscopy for the presence and extent of intraglomerular monocytic infiltration. The sites of infection were cardiac valves (2 cases), ventriculoatrial shunts (2 cases), lungs (2 cases), blood (1 case) and retroperitoneal space (1 case). Seven of the patients had an elevated serum creatinine (1.5-6.5 mg/dl) and all had proteinuria, hematuria and an active urinary sediment. Histochemical investigation using the alpha-naphthyl acetate stain for nonspecific esterase (NSE) was conducted in 7 of the biopsies and showed relatively numerous intraglomerular monocytes in 5 cases. Electron microscopy demonstrated conspicuous monocytic infiltration of glomeruli in the 1 biopsy in which histochemistry was not done and in the 5 cases with high NSE indices (mean number of NSE + cells/glomerulus). The mean NSE index for the group was 4.5 (+/- 3.1) (range = 0.6-10.0). This was compared to the mean NSE indices for other types of diffuse proliferative glomerulonephritis (GN) - GN associated with mixed essential cryoglobulinemia (GN-CRY) (4 cases), membranoproliferative GN, type I (MPGN) (18 cases), post-infectious GN (PIGN) (9 cases) and diffuse lupus GN (GN-SLE) (35 cases). The NSE index for GN-RVI was less than that of GN-CRY (9.1 +/- 5.8) but greater than those of PIGN (3.5 +/- 2.5), GN-SLE (2.6 +/- 2.3) and MPGN (1.3 +/- 1.3). The differences between the GN-RVI index and those of GN-CRY, PIGN and GN-SLE were not significant but the difference between GN-RVI and MPGN was (p less than 0.01, Student's test).     

Fibrillary and immunotactoid glomerulonephritis: Distinct entities with different clinical and pathologic features

BACKGROUND: Controversy surrounds the relatedness of fibrillary glomerulonephritis (FGN) and immunotactoid glomerulonephritis (IT). METHODS: To better define their clinicopathologic features and outcome, we report the largest single center series of 67 cases biopsied from 1980 to 2001, including 61 FGN and 6 IT. FGN was defined by glomerular immune deposition of Congo red-negative randomly oriented fibrils of < 30 nm (mean, 20.1 +/- 0.4 nm). IT was defined by glomerular deposition of hollow, stacked microtubules of > or = 30 nm (mean, 38.2 +/- 5.7 nm). RESULTS: FGN comprised 0.6% of total native kidney biopsies and IT was tenfold more rare (0.06%). Deposits in FGN were immunoglobulin G (IgG) dominant and polyclonal in 96%. IgG subtype analysis in 19 FGN cases showed monotypic deposits in four (two IgG1 and two IgG4) and oligotypic deposits in 15 (all combined IgG1 and IgG4). In IT, deposits were IgG dominant in 83% and monoclonal in 67% (three IgG1 kappa and one IgG1 lambda). FGN patients were a mean age of 57 years, 92% were Caucasian, and 39% were male. At biopsy, FGN patients had the following clinical characteristics (mean, range): creatinine 3.1 mg/dL (0.5 to 14), proteinuria 6.5 g/day (0.8 to 25), 60% microhematuria, and 59% hypertension. Histologic patterns of FGN were diverse, including diffuse proliferative glomerulonephritis (DPGN) (nine cases), membranoproliferative glomerulonephritis (MPGN) (27 cases), mesangial proliferative/sclerosing (MES) (13), membranous glomerulonephritis (MGN) (four), and diffuse sclerosing (DS) (eight). The more proliferative (MPGN and DPGN) and sclerosing (DS) forms presented with a higher creatinine and greater proteinuria compared to MES and MGN. Median time to end-stage renal disease (ESRD) was 24.4 months for FGN and mean time to ESRD varied by histologic subtype: DS 7 months, DPGN 20 months, MPGN 44 months, compared to MES 80 months and MGN 87 months. There was no statistically significant effect of immunosuppressive therapy (given to 36% of FGN patients). By Cox regression (hazard ratio, confidence interval, P value), independent predictors of progression to ESRD were creatinine at biopsy [2.05 (1.55 to 2.72) P < 0.001] and severity of interstitial fibrosis [2.01 (1.05 to 3.85) P = 0.034]. Although IT had similar presentation, histologic patterns, and outcome compared to FGN, it had a greater association with monoclonal gammopathy (P = 0.014), underlying lymphoproliferative disease (P = 0.020), and hypocomplementemia (P = 0.032). CONCLUSION: FGN is an idiopathic condition characterized by polyclonal immune deposits with restricted gamma isotypes. Most patients present with significant renal insufficiency and have a poor outcome despite immunosuppressive therapy, and outcome correlates with histologic subtype. By contrast, IT often contains monoclonal IgG deposits and has a significant association with underlying dysproteinemia and hypocomplementemia. Differentiation of FGN from the much more rare entity IT appears justified on immunopathologic, ultrastructural, and clinical grounds.     

Predictive power of the second renal biopsy in lupus nephritis: significance of macrophages

BACKGROUND: A new Biopsy Index containing the Glomerular Activity (GAI), Tubulointerstitial Activity (TIAI), Chronic Lesion (CLI), and Immunofluorescence (IFI) indices was developed, showing better correlations with clinical and outcome parameters than the National Institutes of Health Activity and Chronicity Indices (AI and CI) in lupus nephritis. This report examines the ability of these indices and individual morphologic variables to predict doubling of serum creatinine (SCr; CRX2). METHODS: Renal biopsies from 71 patients with lupus nephritis with an initial biopsy (Bx1) and systematic control biopsy (Bx2) after six months of therapy were studied. Kaplan-Meier survival curves were developed for each index and morphologic variable at each biopsy. A subset of 30 biopsies was stained with the macrophage marker PGM1. RESULTS: At Bx1, only the TIAI and the quantity of C3 and vascular staining on IF were predictive of CRX2. At Bx2, particularly predictive of CRX2 were the GAI, IFI, Biopsy Index, and BxInfl, a composite variable comprised of all of the inflammatory variables. Among individual variables, glomerular and tubular macrophages correlated the best with clinical and outcome parameters. Crescents and karyorrhexis/fibrinoid necrosis also correlated with outcome. Neither the NIH CI or our CLI, nor the TIAI correlated with outcome. In 30 biopsies stained with PGM1, PGM1+ cells correlated well with glomerular and tubular macrophages identified on routine stains and showed even better correlations with SCr, proteinuria, and progression to renal insufficiency than the latter. A diffuse membranoproliferative (MPGN) pattern was seen in seven patients at Bx1. In four of the seven patients, MPGN disappeared with therapy, and all finished with normal renal function. However, among the three patients in whom MPGN persisted and eight patients in whom MPGN, focal or diffuse, appeared under therapy, six reached end-stage renal disease, and a seventh died with marked renal insufficiency. CONCLUSIONS: The biopsy index and its components correlate modestly with CRX2 at Bx1, but strongly at Bx2, particularly IFI, BxInfl, and glomerular and tubular macrophages. Stains for macrophage markers form a valuable adjunct in interpretation of renal biopsies in systemic lupus erythematosus (SLE). MPGN features do not have an ominous significance at Bx1, but their persistence or appearance under therapy are associated with poor outcome.     

Prognostic significance of surgery and radiation therapy in cases of anaplastic astrocytoma: retrospective analysis of 170 cases

OBJECT: The purpose of this retrospective study was to estimate the prognostic impact of treatment parameters for 170 patients with anaplastic astrocytoma (AA). METHODS: Survival outcome and prognostic factors were analyzed for 170 patients with AA. In the multivariate analysis, site of lesion (frontal or parietal lobe, p = 0.002), extent of surgery (total or subtotal resection, p = 0.001), Karnofsky Performance Scale status (0-2, p = 0.021), age (< or = 50 years, p = 0.024), and total dose of radiation therapy (> 60 Gy, p = 0.029) were significant favorable prognostic factors. In the analysis of groups according to extent of surgery, patients who underwent total or subtotal resection had a significantly more favorable prognosis than did patients who underwent partial resection or biopsy (5-year survival rate 54.0% for total or subtotal resection compared with 17.5% for partial resection or biopsy; median survival time [MST] 62.6 months compared with 22.9 months [p < 0.0001, log-rank test]; hazard ratio [HR] 0.67; and 95% confidence interval [CI] 0.52-0.85 [p = 0.001]). In the analysis of groups according to total radiation dose, the group of patients who received doses greater than 60 Gy had a significantly more favorable prognosis than did the group who received 60 Gy or less (5-year survival rate 45.0% for patients who received doses greater than 60 Gy compared with 21.1% for those receiving 60 Gy or less; MST 48.9 months compared with 21.6 months [p = 0.0006, log-rank test]; HR 0.96; 95% CI 0.93-0.99 [p = 0.029]). CONCLUSIONS: The most important parameter in the treatment of AA was extent of surgery, and total radiation dose was the second most important factor. Resection of as much of the tumor as possible and delivery of a total radiation dose of greater than 60 Gy seem to be required for local control of AA.     

Correlation of renal histology with outcome in children with lupus nephritis

We assessed renal histological features in 20 children with diffuse proliferative lupus nephritis (DPLN) to determine whether they were useful in predicting clinical outcome. Renal biopsies were analyzed by assigning scores indicating an activity index (AI) and chronicity index (CI). Clinical assessment of renal function at biopsy and outcome were graded according to urinalysis, serum creatinine, need for dialysis and/or transplantation, and/or death from end-stage renal failure. Renal function at biopsy correlated significantly with AI and CI. Serum complement (C3 and C4) correlated significantly with CI but not with AI. The usefulness of the clinical grading system was confirmed in ten patients who underwent repeat biopsies. Of these, four converted from DPLN to mesangial or membranous lupus and showed improvement in their grade, while only one of the six with DPLN on both biopsies improved. After a mean follow-up of 4.0 years, 14 of the 20 patients showed clinical improvement, four were unchanged, and two were worse. CI predicted clinical outcome (P less than 0.01) but AI did not. Histologic scores of AI and CI obtained from renal biopsies showing DPLN may be useful in predicting therapeutic responses and designing prospective clinical trials to determine optimum management of children with DPLN.     

Quantitative digital histochemistry with methenamine silver staining in renal allograft biopsies excluding pure chronic allograft nephropathy cases

Deterioration of renal function is correlated with irreversible damage in chronic diseases. Recently we described a digital quantitative histochemistry method, relying on periodic acid methenamine silver (PAMS) staining to determine the chronic renal lesions. This index was strongly correlated with progressive deterioration of renal function in grafts with chronic allograft nephropathy (CAN). Herein the method has been applied to a cohort of renal allografts which were biopsied for various reasons, we sought to highlight its value to quantify chronic graft damage. Forty-four renal allograft biopsies from 37 patients with elevated serum creatinine values (SCr) underwent light microscopic image analysis (Mediscope, Dokuz Eylül University, Clinical Engineering Department, Izmir, Turkey) of the PAMS-stained area percentage (SAP). SCr was recorded at four intervals to overcome acute effects: the under SCr value before (SCr1) and after a biopsy within 3 months (SCr3), SCr at the time of the biopsy (SCr2), and the latest value (SCr4). The PAMS-SAP scores were strongly associated with increased interstitial fibrosis and tubular atrophy Banff scores (Kruskal-Wallis test, P = .006 and P = .003, respectively). There was a moderate positive correlation between PAMS and SCr3 (Pearson correlation test, P = .04, r = .312), and a strong positive correlation between time from transplantation to biopsy (Pearson correlation test, P < .000, r = .532). The present results show that PAMS-SAP seems to be of value to quantify renal scarring in allograft biopsies, reflecting four compartments. The strong correlation with time is noteworthy especially as a probable reflection of aging of the renal allograft.     

Molecular markers and their prognostic impact in patients with advanced prostate cancer undergoing intermittent androgen suppression

OBJECTIVE: Tumour features were evaluated during intermittent androgen suppression (IAS), and their prognostic impact on the first off-treatment time was analysed. PATIENTS AND METHODS: Twenty patients with advanced prostate cancer underwent three consecutive prostate biopsies during the first cycle, namely at the beginning of androgen deprivation, 8 months after continuous therapy and at the time of prostate-specific antigen (PSA) progression above 20 ng/ml. Biopsy specimens were immunohistochemically processed and analysed for the apoptotic index (AI), Ki-67, p53 and Bcl-2 to investigate eventual changes over time. Correlations and regression analysis were performed to assess the prognostic significance of clinical and pathological parameters in predicting the first off-treatment time. RESULTS: In contrast to the AI, p53 and Bcl-2, Ki-67 was the only marker that significantly changed over time (P=0.008). The first off-treatment time correlated significantly with pretreatment PSA (r=-0.594; P<0.01), testosterone recovery time (r=0.590; P=0.013) and biopsy grade (r=-0.738; P<0.01); only the latter gaining an independent factor in the multivariate analysis (P=0.022). CONCLUSIONS: During IAS, Ki-67 was the only molecular marker that consistently changed over time. However, it did not correlate with off-treatment time that was predicted independently by the initial biopsy grade only. First off-treatment time was best predicted by clinical parameters and molecular markers from needle biopsies did not further contribute to a better patient selection.     

Renal flares in 91 SLE patients with diffuse proliferative glomerulonephritis

BACKGROUND: Even when treated with current protocols, 25 to 30% of systemic lupus erythematosus (SLE) patients with diffuse proliferative glomerulonephritis (DPGN) evolve to end-stage renal disease (ESRD). The occurrence of renal flares is considered to be an important risk factor for the evolution to ESRD. The aim of this retrospective study was to evaluate the incidence and prognostic significance of renal flares in SLE patients with DPGN and to identify predictors for the occurrence of flares. METHODS: Ninety-one SLE patients were selected for study based on the following criteria: (a) evidence of renal involvement, (b) a follow-up of at least 6 months after the renal biopsy, and (c) a steady improvement in renal manifestations after the biopsy lasting for at least three months. RESULTS: Renal flares occurred in 54% of the patients after renal biopsy and appropriate treatment. A younger age at the time of renal biopsy correlated with the occurrence of renal flares. A high activity index (> or =10) and karyorrhexis on histology correlated with the occurrence of nephritic flares. Twenty-seven percent of the patients developed ESRD. The number of renal flares, nephritic flares, and "early" proteinuric flares (that is, those occurring in the first 18 months after renal biopsy) as well as serum creatinine levels, karyorrhexis, and chronicity index on renal histology were correlated with doubling serum creatinine. CONCLUSIONS: Our results suggest that (a) a distinct subgroup of SLE patients exists, made up of younger patients with extensive, active lesions on renal biopsy, who are at higher risk for renal flares, (b) renal flares represent important predictors of doubling serum creatinine.     

Renal mRNA levels as prognostic tools in kidney diseases

Molecular biologic techniques are currently considered as new diagnostic and prognostic parameters with a sensitivity and specificity exceeding those of histologic and functional data currently used in clinical practice. The results in various clinical settings have been of limited value up to now. This study is an investigation of the use of tissue levels of RNA determined in routine clinical kidney biopsies as prognostic tools. The focus was on RNA encoding for molecules known to be involved in the pathogenesis of renal disorders. Fresh kidney biopsy tissue was obtained from 52 patients with various renal diseases. The GFR was followed for 12 mo. The extent of glomerulosclerosis and interstitial fibrosis in the biopsies was determined with quantitative digital image analysis. Glomerular and tubulointerstitial compartments from each biopsy specimen were separated, and mRNA levels of TGF-beta, collagen I, collagen IV, and fibronectin were quantitated by real-time PCR. Correlations, along with 95% confidence intervals (CI), between all variables tested at time biopsy were determined. To assess their prognostic value, these variables were correlated with the slope of GFR within several time intervals after biopsy. In addition, to evaluate the predictive value of the variables for outcome in individual patients, differences for each variable were tested between patients showing progressive decline in renal function (slope GFR < 0) and patients showing stable or improving renal function over time (slope GFR >or= 0). In chronic renal diseases, the extent of histologic damage correlated with the GFR at the time of biopsy (r = -0.44; CI -0.68 to -0.11), but it did not correlate with the slope expressing a change in GFR after the biopsy. Tubulointerstitial TGF-beta mRNA levels correlated with the rate of change in GFR between time of biopsy and 1 mo later (r = 0.41; CI, 0.07 to 0.67). The GFR at the time of biopsy correlated with the slope of change in GFR between time of biopsy and 12 mo later (r = -0.50; CI, -0.73 to -0.18). In chronic renal diseases, glomerular fibronectin mRNA levels, in comparison with the GFR at time of biopsy, correlated relatively strongly with the slope of change in GFR between 3 and 12 mo (r = 0.50; CI, 0.16 to 0.74). Patients with favorable renal outcome after 12 mo showed significantly higher TGF-beta mRNA levels and lower proteinuria levels at time of biopsy (P < 0.05) than patients with a progressive decline in renal function. This study shows that mRNA levels measured in kidney biopsies can function as prognostic tools in human renal diseases. In particular, relatively high levels of tubulointerstitial TGF-beta mRNA and glomerular fibronectin mRNA are associated with less deterioration in renal function.     

Multivariate analysis of prognostic factors and effect of treatment in patients with IgA nephropathy

BACKGROUND: Although the clinical and histological prognostic factors of IgA nephropathy have been investigated in detail, the value of treatment in terms of renal outcome is not well understood. METHODS: The authors examined data from 237 patients with IgA nephropathy (age 31.4+/-13.5 years, mean+/-SD) who had been followed-up for at least six months (follow-up periods, 62.3+/-45.5 months). The authors initially tested the significance of prognostic factors (age, sex, systolic blood pressure, proteinuria, serum creatinine, and histological severity) and treatment strategies (steroid therapy, renin-angiotensin system inhibitors and tonsillectomy) on renal outcome with univariate analysis, then evaluated the findings using the Cox proportional hazards model. RESULTS: Univariate and multivariate analyses showed that among the prognostic variables, a high level of serum creatinine at renal biopsy, large amounts of proteinuria, and extensive histological injury were significant risk factors for end-stage renal failure. Kaplan-Meier analysis showed that the renal survival rates associated with these factors were significantly poorer depending on their severity. Univariate analysis revealed that tonsillectomy was the only significant treatment that contributes to the maintenance of renal survival. Moreover, urinary abnormalities disappeared at a significantly higher frequency when patients were treated by tonsillectomy. The Cox proportional hazards model showed that steroid therapy independently contributed to improve renal prognosis in addition to tonsillectomy, and the hazard ratios were 0.26 (95% CI, 0.07 to 0.93) and 0.37 (95% CI, 0.14 to 0.99), respectively. CONCLUSION: Steroid therapy and tonsillectomy can independently improve renal outcome in patients with IgA nephropathy.     

Blood pressure and graft outcome in renal transplantation

To investigate the effects of blood pressure (BP) on kidney function, we reviewed 116 patients who had a median follow-up of 40.5 months. Systolic and diastolic hypertension (HTN) at month 6 resulted in significantly higher serum creatinine (SCr) levels at 1 year, compared with patients with normal BP, namely, 2.2 versus 1.4 mg/dL (P = .0001) and 1.87 versus 1.5 mg/dL (P = .04), respectively. Mean systolic and diastolic BP at the end of 1 and 6 months were significantly higher among patients who had returned to hemodialysis or who had an SCr > or =2 mg/dL at their last follow-up. Mean age, mean donor age, donor type, and sex had no significant effect on graft function. Patients receiving Rapamune-based treatment (n = 9) had no graft failure; graft outcomes were similar between cyclosporine-based and tacrolimus-based immunosuppression therapy. Patients with biopsy-proved acute rejection showed significantly lower graft survival. By multivariate analysis, systolic HTN at the end of 1 month (P = .006) and 6 months (P = .01), and diastolic HTN at the end of 6 months (P = .04) were independent risk factors for graft outcome. Actuarial 5-year graft survival was 95%, versus 76% in patients with normal BP versus systolic HTN at 1 month, respectively (P = .02). A significant difference in 5-year graft survival was observed between patients with normal diastolic BP and diastolic HTN at 6 months (95% versus 67%, respectively; P = .001). Since systolic and diastolic BP at different times before and after transplantation correlate with graft function, more attention should be paid to maintain normal BP in patients with renal transplants.     

The spectrum of diseases associated with necrotizing glomerulonephritis and its prognosis

Necrotizing glomerulonephritis (NGN) represents small-vessel vasculitis in the kidney. To assess the diseases associated with necrotizing glomerular changes and their prognosis we studied all 32 patients who had this histologic finding on kidney biopsy from 1969 to 1982 and compared them to those patients who had crescentic, diffuse, or focal and segmental glomerulonephritis without necrosis (n = 29). The diseases associated with NGN were systemic lupus erythematosus (n = 6/15), Henoch-Sch?nlein purpura (n = 3/4) Goodpasture's syndrome (n = 4/7), Wegener's granulomatosis (n = 6/6), polyarteritis (n = 4/5), infective endocarditis (n = 2/3), and idiopathic rapidly progressive glomerulonephritis (n = 7/21). Necrotizing glomerulonephritis occurred significantly more often in the vasculitides than in all the other disorders put together. The most difficult diagnosis problem occurred in patients with renal disease and pulmonary hemorrhage (n = 9), in three of whom diagnosis was uncertain even after autopsy (two autopsies done within one month and one within three months of presentation). A fourth patient had a linear staining for IgG along the glomerular basement membrane (GBM) on kidney biopsy but was subsequently diagnosed as having Wegener's granulomatosis. Comparison of patients with without NGN revealed no difference in outcome (death or dialysis) one year after biopsy (38% v 43%) or in serum creatinine levels one year later (4.6 v 4.8 mg/dL). The prognostic effect of NGN was not obscured by unequal distribution of other adverse prognostic factors in the two groups. The most important prognostic characteristics we identified for outcome were serum creatinine at biopsy (chi 2 = 24.0, P less than .0004) and the sum of activity and chronicity indexes on biopsy (chi 2 = 12.7, P = .0004). These variables were similarly distributed in patients with and without necrosis, mean serum creatinine levels at biopsy being 4.3 v 4.2 mg/dL and sum of indexes 7.8 v 8.0. Other factors such as clinical diagnosis and therapy were not important prognostically and therefore could not explain our results. We conclude that NGN in patients with active proliferative glomerulonephritis has multiple causes. Diagnostic difficulties occurred in those with anti-GBM-negative pulmonary hemorrhage. The appearances of small-vessel vasculitis in the kidney did not appear to have prognostic significance.     

Atherosclerotic risk factors and renal function in the elderly: the role of hyperfibrinogenaemia and smoking. Results from the Italian Longitudinal Study on Ageing (ILSA).

BACKGROUND: We examined associations between cardiovascular diseases and risk factors with pathological levels of and significant changes in serum creatinine (SCr) in a large prevalence phase and longitudinal phase community-based sample of an elderly Italian population (ILSA Study) showing no clinical evidence of renal impairment. METHODS: The prevalence phase was performed on 2981 subjects, aged 65-84 years, who were negative for renal diseases, had available SCr values and had complete clinical information on their cardiovascular risk factors. Of these, 371 were considered 'healthy' since they were not affected by cardiovascular diseases or diabetes, whereas 2610 tested positive for cardiovascular diseases and were considered 'diseased'. The sex-specific 95th percentiles for SCr (cut-off points) were calculated in the healthy reference sample to define the upper limit for normal SCr values. The distribution and prevalence of diseased subjects having values over the cut-off point values were then estimated. Associations between values over the cut-off point levels and pathological or clinical conditions were analysed from the diseased sample. The longitudinal phase was carried out on 1906 subjects who had SCr values and sufficient clinical information for our investigation. The incidence of an increase of >26.5 micromol/l of SCr was evaluated in the longitudinal cohort. RESULTS: In healthy subjects, the 95th SCr percentiles (cut-off points) were 123.8 micromol/l in men and 97.2 micromol/l in women. In diseased subjects, the prevalence of SCr values over the cut-off point was 4.6% in men and 9.3% in women. In logistic regression analysis, independent variables that correlated with over the cut-off point SCr values were: age >75 years [odds ratio (OR) = 2.2; 95% confidence interval (CI) = 1.5-3.4], atherosclerosis of the lower limbs (OR = 2.0; 95% CI = 1.2-3.3), cerebrovascular disease (OR = 1.9; 95% CI = 1.2-3.3), angiotensin-converting enzyme (ACE) inhibitor medication (OR = 1.8; 95% CI = 1.2-2.8), fibrinogen values >3.5 g/l (OR = 1.2; 95% CI = 1.2-2.7) and diuretic treatment (OR = 1.6; 95% CI = 1.1-2.4). After a mean 3.6 years follow-up, multiple logistic regression analysis showed that risk factors for pathological loss of renal function (rise of SCr >26.5 micromol/l) were: current smokers >20 cigarettes/day (OR = 2.3; 95% CI = 1.0-5.3), fibrinogen values >3.5 g/l (OR = 2.2; 95% CI = 1.6-3.3), diabetes (OR = 1.8; 95% CI = 1.1-2.8), age >75 years (OR = 1.7; 95% CI = 1.2-2.4) and isolated systolic hypertension (OR = 1.6; 95% CI = 1.0-2.6). The loss of renal function examined during the longitudinal phase appeared to be independent of baseline SCr levels. CONCLUSION: The present prevalence and longitudinal studies show that age-associated decline in renal function in elderly subjects is associated with co-existing cardiovascular diseases and risk factors. These observations should be incorporated into clinical practice since some of the factors detrimental to kidney function, such as smoking, altered fibrinogen levels and elevated systolic blood pressure, can be prevented and/or modified when appropriate measures are taken.     

Relationship between serum B-cell activating factor levels and clinicopathology in children with lupus nephritis

Objective To analyze the relationship between the serum B-cell activating factor (BAFF) levels and clinical characters and pathological features in children with lupus nephritis (LN). Methods ELISA was used to detect the serum BAFF (sBAFF) levels of the 54 LN children diagnosed in the First Affiliated Hospital, Sun Yat-sen University during October 1, 2014 to December 31, 2016 and with complete clinical data. According to whether glucocorticoid or immunosuppressive agents has been used at their first admission, patients were divided into treated group (n=44) and non-therapy group (n=10). According to the renal response after induction treatment for 6 months, patients were divided into remission group (n=20) and non-response group (n=34). According to whether there was renal recurrence, they were divided into recurrence group (6 cases) and non-recurrence group (48 cases). According to renal biopsy, patients were divided into class-Ⅲ, class-Ⅳ and class-Ⅴ group. Another 15 healthy children were taken as a control group. The correlations between sBAFF and clinical manifestation, laboratory examination, renal biopsy and clinical outcome were analyzed. Results (1) Compared with the control group, the sBAFF was significantly increased in LN group (t=3.821, P＜0.001). Compared with the non- neuropsychiatric systemic lupus erythematosus (NPSLE) group, sBAFF was significantly increased in NPSLE group (t=2.202, P=0.032). (2) Compared with that in treated group, sBAFF was significantly higher in untreated group (LSD-t=2.309, P=0.025). Compared with non-response group, sBAFF was significantly decreased in response group (LSD-t=2.035, P=0.046). (3) No significant difference was observed between class-Ⅲ, class-Ⅳ and class-Ⅴ pathological classification group (F=1.080, P=0.459). sBAFF in LN children was not significantly correlated with the active index (AI) or chronic index (CI) of Austin index (r=-0.273, P=0.063; r=0.150, P=0.314). (4) In LN children, sBAFF has positive correlation with ESR and IgG level (r=0.289, P=0.036; r=0.340, P=0.017) and negative correlation with WBC (r=-0.337, P=0.013). Multiple linear regression model showed that serum IgG level (β'=0.517, P=0.001) and renal response (β'=-0.271, P=0.037) were independent influencing factors of sBAFF level. Conclusions Renal remission and serum IgG levels in LN children are influencing factors of sBAFF levels. sBAFF is helpful to clinical assessment on renal response of LN children.     

肾功能不全的IgA肾病患者临床表现与病理特点分析

目的分析肾脏活体组织检查（简称：肾活检）时肾功能异常的IgA肾病患者的临床表现与病理特点。方法选择我院经肾活检确诊的190例IgA肾病患者为研究对象,以其患者血肌酐（SCr）130μmol／L为界分为2组：肾功能正常组（SCr〈130μmol／L）128例和肾功能异常组（SCr≥130μmol／L）62例。同时对其肾脏病理进行半定量评分,比较2组患者的临床病理特点,并且通过回归分析与其肾功损害相关的因素。结果与肾功能正常组相比,肾功能异常组男性比例明显增高（72．6％1;L28．9％,P〈0．01）,年龄更大[（34±10）岁比（30±9）岁,P〈0．01],病程更短[（11±17）]个月比（20±41）个月],同时收缩压更高[（141±19）比（123±17）mmHg,P〈0．01],24h尿蛋白定量增多[（3．31±2．70）g比（2．25±2．19）g,P〈0．01]。同时其患者肾脏病理反映慢性病变的指数均明显增高。多因素分析还显示,与肾活检时肾功能异常密切相关的危险因素包括男性,年龄增大,收缩压增高,24h尿蛋白定量增多,以及肾小管萎缩和间质纤维化指数增高。结论肾活检时肾功能异常的IgA。肾病患者临床表现和肾脏病理改变均明显加重,肾小管萎缩和间质纤维化指数增高与IgA肾病患者肾活检时肾功能异常独立相关。     

Prognostic Factors in Supratentorial Ganglioglioma

Summary  Although gangliogliomas are often associated with long survival, efforts to identify specific prognostic factors in these tumors have been largely unsuccessful. To identify factors associated with long survival, we retrospectively reviewed 42 cases of supratentorial ganglioglioma surgically treated at our institution since 1985. Data analysis included Kaplan-Meier survival curves and log-rank tests of the effects of individual variables. The Cox proportional hazards method was used to fit a model incorporating several variables simultaneously.  The 42 cases included 21 male and 21 female patients with an average age at surgery of 31 years. Length of follow-up averaged 48 months. Ten patients died an average of 38 months after surgery. Factors found to have a significant correlation with mortality were older age at diagnosis (P=0.012), male gender (P=0.034), and malignant glial features (P=0.020). Presenting symptoms, location of tumor, adjuvant radiation therapy, and extent of surgical resection were not significantly related to survival.  These results are the first to demonstrate an association between prognostic factors and outcome in patients with supratentorial ganglioglioma.     

Clinicopathologic study on prognostic markers in IgA nephropathy

BACKGROUND/AIM: Few prognostic markers have found general acceptance in IgA nephropathy (IgAN). The aim of the present study was to search for significant predictor(s) at the time of biopsy. METHODS: Fifty-five patients with IgAN undergoing evaluation and treatment at our institution were examined regarding clinicopathologic features at the time of renal biopsy and, if possible, at follow-up. Factors predictive of outcome were evaluated. Renal histopathology was quantified using a glomerulosclerosis index (GSI), a tubulointerstitial index (TII), and a crescent index (CI). RESULTS: The serum creatinine concentration (S-Cr) showed positive correlations with proteinuria and serum total cholesterol concentration, as well as with histopathologic findings. Heavy proteinuria (> or =3.0g/24 h) was associated with higher S-Cr and greater severity of pathologic abnormalities than with milder proteinuria. At follow-up, 6 patients progressed to chronic renal insufficiency, in whom the S-Cr increased by at least 50% to reach or exceed 1.5 mg/dl (132.6 micromol/l). By univariate analysis, elevated GSI, TII, and S-Cr, presence of nephrotic syndrome, elevated CI, and elevated total cholesterol were found to be negative predictors, in descending order of odds ratio. In multivariate analysis, however, only TII independently predicted unfavorable outcome. Conclusion: Renal biopsy in IgAN may be the most powerful predictor for renal outcome; an advanced tubulointerstitial lesion is unfavorable.