Evaluation of metabolic risk marker in obesity-related glomerulopathy.

OBJECTIVE: Insulin resistance is a common metabolic abnormality, which increases the risk of renal events in obesity. The present study is aimed to examine the relation between metabolic factors and obesity-related glomerulopathy (ORG), and then compare the risk markers of insulin resistance for clinical prediction. METHODS: A total of 112 cases with proven renal ORG and 135 age- and gender-matched lean controls were included. The degree of proteinuria, endogenous creatinine clearance rate, body mass index, amylin, fasting glucose, insulin, lipid and lipoprotein concentrations were measured during the steady state. RESULTS: The patients with ORG were clinically characterized by increased body mass index and proteinuria, with higher levels of amylin, homeostasis model assessment of insulin resistance (HOMA-IR), insulin, glucose, and lipid proteins when compared with the lean controls. Multiple logistic regression analysis revealed that amylin and HOMA-IR were significantly associated with the prevalence of ORG. In patients with ORG, proteinuria level correlated with amylin, total cholesterol, fasting insulin, and HOMA-IR. Moreover, proteinuria correlated positively with HOMA-IR and amylin in a multiple regression analysis. In addition, the endogenous creatinine clearance rate did not correlate with any metabolic marker. CONCLUSION: This study suggested that screening for HOMA-IR might have predictive value for renal damage in obese patients. In addition to insulin resistance, amylin also showed positive effects on evaluation of such renal impairment.

Renal biopsy in type 2 diabetes: timing of complications and evaluating of safety in Chinese patients.

AIM: It has been recognized that renal lesions in patients with diabetes often have other causes of renal damage concomitantly. Renal biopsy is a valuable tool to provide histological evidence. However, the safety in patients with type 2 diabetes receiving renal biopsy is not well evaluated. This study was conducted to monitor the dynamic complications and to evaluate the safety of biopsy in diabetic patients. METHODS: A prospective observation was performed on 130 patients with type 2 diabetes and 150 patients not undergoing renal biopsy. The complications were monitored at 4 h, 8 h, 24 h, 48 h and 72 h sequentially after biopsy. RESULTS: Haematoma was observed in 34 (26.15%) patients with diabetes and 50 (33.33%) in controls (P=0.19). The timing of large haematoma peaked at 4 h. Gross haematuria occurred in 12 (9.23%) diabetic patients and eight (5.33%) controls (P=0.207). It happened mainly within 8 h. Renal pathological diagnosis showed 96 (73.85%) cases with diabetic nephropathy and 34 (26.15%) cases with non-diabetic renal disease. CONCLUSION: Renal biopsy in patients with type 2 diabetes is safe. The frequency of complications after renal biopsy in diabetes is no higher than those without diabetes. The complications mostly happened within 8 h, especially within 4 h. Biopsy is also very necessary to rule out other chronic renal diseases in diabetes.

Late onset lupus nephritis: analysis of clinical manifestations and renal pathological features in Chinese patients.

The objectives of the study are to analyze the clinical and pathological features of 35 Chinese patients with late onset lupus nephritis (LN) in a single center. All the LN patients followed-up in our lupus clinic center from 1986 to 2008 were enrolled in this retrospective study. Thirty-five patients with a disease onset beyond the age of 50 years were identified. One hundred systemic lupus erythematosus (SLE) patients who had their disease onset before the age of 50 years were randomly recruited as controls. All of them received renal biopsy. The histological classifications were categorized according to 2003 International Society of Nephrology/Renal Pathology Society (ISN/RPS) classification. All of patients were Han Chinese. The mean age of onset of SLE for late onset and the control groups were 55.7 ± 6.5 years (range: 50-76) and 28.9 ± 7.6 years (range:18-48).The female to male ratio was smaller in the late onset SLE group, 2.9-1, compared with 7.3-1 in the control. The patients with hypertension in late onset LN were much more than that in control group. The renal histological classes showed no significant difference between the two groups. Classes IV, V, IV + V were common in late onset LN patients. There were no significant differences in extra renal manifestations except for a lower prevalence of malar rash, a higher leukopenia and skin vasculitis in the late onset patients. As to the immunological features, serum antineutrophil cytoplasmic antibodies (ANCA) and SSA positivity were more common in late onset LN patients. The patients with hypertension in late onset LN were much more than that in control group. The renal histological classes showed no significant difference between the two groups. Leukopenia and serum ANCA were more common. The results suggest a more severity of the disease in late onset LN.

Clinicopathological features and prognosis of Chinese patients with acute post-streptococcal glomerulonephritis.

AIM: To investigate clinicopathological and prognostic differences between adults and children with acute post-streptococcal glomerulonephritis (APSGN). METHODS: A retrospective case series of 112 patients with APSGN was undertaken. Patients were divided into two groups according to age: adults aged more than 17 years and children aged less than 15 years. RESULTS: The incidence of APSGN, especially in adults, has decreased in the past three decades. Children have had a higher incidence of macroscopic haematuria than adults (58.3% vs 32.7%, P < 0.05). Laboratory test showed that red blood cell count of urine sediment in children was more significant. On light microscopy, adults had more global glomerulosclerosis, tubular basement membrane thickening, tubular atrophy and interstitial fibrosis, while children had more glomerular infiltrating neutrophils and monocytes and cellular casts. Immunofluorescence microscopy showed that classical staining was seen more in children. The short-term prognoses were good in both children and adults. But the recovery rate of proteinuria in children was faster than that in adults. CONCLUSION: Adults with APSGN had similar clinical features as children except that children had more significant haematuria. On pathology, adults had more outstanding chronic changes by light microscopy and more untypical staining by immunofluorescence.

Obesity-related glomerulopathy: body mass index and proteinuria.

BACKGROUND AND OBJECTIVES: Obesity-related glomerulopathy (ORG) is an increasing cause of end-stage renal disease, but evidence concerning the effects of treatments is rather limited. This study was aimed at exploring the renoprotective effects of weight loss on patients with ORG. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: A total of 63 patients with renal biopsy-proven ORG had food and exercise intervention in the physician-supervised weight loss program and were divided into three groups on the basis of the percentage of weight change from baseline to follow-up: significant weight loss (>3% reduction in body mass index [BMI]), stable weight, or significant weight gain (>3% increase). Metabolic parameters and renal lesions were evaluated regularly for 2 years. RESULTS: After 6 months, 27 patients lost weight by 8.29 +/- 4.00%, with a mean decrease in proteinuria of 35.3%, whereas 24 months later, 27 patients achieved a 9.20 +/- 3.78% reduction in BMI and a 51.33% reduction in urine protein secretion. The levels of serum triglyceride, serum uric acid, and BP were also decreased. Contrarily, in patients with increased BMI, urine protein was increased by 28.78%. Correlation analysis showed proteinuria was associated with BMI, serum triglyceride, and uric acid, and multivariate regression analysis indicated the changes in BMI were the only predictor of proteinuria (P < 0.01). CONCLUSIONS: Weight loss intervention benefited remission of proteinuria in patients with ORG, whose function could not be replaced by conventional pharmacotherapy.

Triptolide reduces proteinuria in experimental membranous nephropathy and protects against C5b-9-induced podocyte injury in vitro.

Membranous nephropathy is a major cause of nephrotic syndrome in adults where podocyte injuries were found to mediate the development of proteinuria. Triptolide, a major active component of Tripterygium wilfordii Hook F, has potent immunosuppressive, anti-inflammatory and antiproteinuric effects. To study its antiproteinuric properties, we established an experimental rat model of passive Heymann nephritis and a C5b-9 injury model of podocytes in vitro. Treatment or pretreatment with triptolide markedly reduced established proteinuria as well as the titer of circulating rat anti-rabbit IgG antibodies in these nephritic rats, accompanied by a reduction in glomerular C5b-9 deposits. Expression of desmin, a marker of podocyte injury, diminished after triptolide treatment, whereas quantitative analysis of mean foot process width showed that effacement of foot processes was substantially reversed. In in vitro studies we found that triptolide deactivated NADPH oxidase, suppressed reactive oxygen species generation and p38 mitogen-activated protein kinase, and restored RhoA signaling activity. Triptolide did not interfere with the formation of C5b-9 on the membrane of podocytes. Thus, triptolide reduces established heavy proteinuria and podocyte injuries in rats with passive Heymann nephritis, and protects podocytes from C5b-9-mediated injury.

Crush syndrome after the Wenchuan earthquake: new experience with regional citrate anticoagulation continuous veno-venous hemofiltration.

PURPOSE: Acute renal failure (ARF) related to crush syndrome is usually treated with hemodialysis. Continuous veno-venous hemofiltration (CVVH) has seldom been adopted in this situation due to the main drawback of continuous anticoagulation. The purpose of this study was to evaluate the effectiveness and safety of regional citrate anticoagulation (RCA)-CVVH in two crush syndrome patients following the Wenchaun earthquake. METHODS: Two victims from the Wenchuan earthquake in Southwest China were admitted to our hospital on May 23, 2008, 11 days after their injury. The total entrapment time under the rubble was 5.5 and 22.5 hrs respectively. They remained oliguric on admission, in spite of vigorous treatment in the local hospital including aggressive fluid infusion, fasciotomy and intermittent hemodialysis. On admission, their serum myoglobin levels were 765 and 829 ng/mL, respectively. Further debridement and drainage were performed. RCA-CVVH was conducted; the citrate containing substitution fluid was infused in a pre-dilution manner at a rate of 4 l/h; calcium was infused through a separate access to the venous inlet of the double lumen catheter. The infusion rate was adjusted according to the serum ionized calcium and whole blood activated clotting time (WBACT). A low dose of low molecular weight heparin (LMWH) was infused at the rate of 150 approximately 300 U/h simultaneously for anticoagulation after anemia had been corrected and their wounds were stable. RCA-CVVH was substituted by conventional CVVH and LMWH anticoagulation when case 2 complicated with hypoxia. RESULTS: RCA-CVVH was well tolerated, hemodynamic status was stable, and no complications related with RCA-CVVH were noted. The body temperature and WBC decreased to normal range, while anemia and hypoalbuminia were corrected. The levels of serum myoglobin and creatine phosphokinase were also decreased to normal range. Their urine volume increased after 20 and 22 days of oliguria and the tubular function of the patients recovered well. Although the second case encountered acute cholecystitis and acute lung injury in the hospital, both the patients recuperated and neither of them underwent amputation. CONCLUSIONS: The present two crush patients have been successfully treated, but due to the limits of the small sample, it is difficult to generalize whether RCA-CVVH is safe enough for crush syndrome with a high risk of bleeding diathesis. Additional investigation with a larger number of patients is required. Fluid equilibrium, nutritional support, prevention of bleeding and infection are fundamental in this situation.

Improvement of immune dysfunction in patients with severe acute pancreatitis by high-volume hemofiltration: a preliminary report.

OBJECTIVE: The aim of this study was to investigate the effect of high-volume hemofiltration (HVHF) on ameliorating immune dysfunction in patients with severe acute pancreatitis (SAP). METHODS: Twelve patients diagnosed with SAP admitted to the intensive care unit of general surgery, Jinling Hospital, from January 2004 to December 2006 were included in this study. They were assigned to the standard medical therapy group (SMT group, n=4) or HVHF group (n=8) immediately after enrollment, in a 1:2 ratio. The SMT group were given standard treatment for SAP, while the HVHF group were given standard as well as 72-hour HVHF treatment initiated within 2 hours after enrollment. Patients in the 2 groups were comparable for the baseline clinical parameters. All patients were monitored over a 72-hour observation period for continuous clinical status, blood cell counts including monocytes, CD4+ and CD8+ T cells, and HLA-DR expression on monocytes. Blood samples were collected from those patients at 0, 6, 12, 24, 48, and 72 hour after enrollment for measurement of plasma Th1-type cytokines (interleukin-1 [IL-1], IL-2, interferon-gamma [IFN-gamma], and tumor necrosis factor-alpha [TNF-alpha]) and Th2-type cytokines (IL-4, IL-5, IL-6, IL-IO, and IL-13) using ELISA. RESULTS: Within 72 hours, all measured cytokines except IL-4 were maintained at high levels, accompanied with a low level of peripheral monocytes, CD4+ and CD8+ T cell counts, and HLA-DR expression. Seventy-two hours later, plasma cytokines IFN-gamma, IL-1, IL-2, IL-5, IL-10, and IL-13 (p<0.05), but not TNF-alpha and IL-6, in patients in the HVHF group were significantly reduced, while there was no change for these parameters in the SMT group. Plasma levels of IFN-gamma, TNF-alpha, IL-1, IL-2, IL-5, and IL-13 in the HVHF group were significantly lower than those in the SMT group. Peripheral CD4+ and CD8+ T cells, monocyte count, and HLA-DR expression were increased significantly (p<0.05) only in the HVHF group, not in the SMT group. HLA-DR expression in the HVHF group was significant higher than that in the SMT group (p<0.05). CONCLUSIONS: HVHF significantly reduced plasma inflammatory cytokine concentrations including those of IFN-gamma, TNF-alpha, IL-1, IL-2, IL-5, and IL-13, while it increased monocyte HLA-DR expression in patients with SAP. The association of plasma cytokine reduction and cellular immune function recovery and clinical outcome needs further investigation.

Mercury-induced membranous nephropathy: clinical and pathological features.

BACKGROUND AND OBJECTIVES: Long-term contact with mercury may induce membranous nephropathy (MN); however, the clinical pathologic features and pathogenesis of mercury-induced MN have not been investigated. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: The present study retrospectively evaluated 11 cases of mercury-induced MN to analyze its causes and its clinical and pathologic features. RESULTS: A total of 10 women and 1 man ages 15 to 45 years were enrolled in the present study. Mercury exposure was caused by mercury-containing pills (five patients), skin lightening cream (four patients), hair-dyeing agents (one patient), and mercury vapor (one patient). The duration of contact with mercury ranged from 2 to 60 months, and the urinary mercury concentrations were 1.5 to 50 times higher than reference values. All patients presented with proteinuria and normal renal function; three had nephrotic syndrome. Light microscopy revealed thickened glomerular basement membrane and mildly proliferative mesangial cells. Acute tubulointerstitial injury occurred in three patients. The immunofluorescence findings showed granular deposits of IgG and C3 along the glomerular capillary wall, mostly accompanied by deposits of C4 and C1q. IgG1 and IgG4 (predominantly IgG1) deposits were observed along the glomerular capillary loops. Nine patients reached complete remission in follow-up after withdrawal from mercury exposure. CONCLUSIONS: Deposits of IgG1 subclasses in renal tissues indicated that the pathogenesis of mercury-induced MN differs from that of idiopathic MN. It is important that clinicians are aware that mercury exposure should be considered a possible cause of membranous nephropathy.

Rhein improves renal lesion and ameliorates dyslipidemia in db/db mice with diabetic nephropathy.

Rhein (4,5-dihydroxyanthraquinone-2-carboxylic acid) is purified from rhubarb (Rheum officinale), a widely used traditional Chinese herb. In our previous studies, rhein was shown to be effective in ameliorating diabetic renal pathological changes and attenuating hyperlipidemia. Statins have also been proven to ameliorate renal pathological changes associated with diabetic nephropathy (DN) through lipid-dependent and -independent mechanisms. We here study the protective and regulatory effects of rhein on renal injury and dyslipidemia in db/db mice with DN, using simvastatin as the control, and provide information on the mechanisms by which rhein protects against renal damage from DN. The results indicated that urinary albumin excretion (UAE) was reduced after 8 weeks of treatment in the rhein group, and 12 weeks in the simvastatin group. The morphometric analysis revealed that levels of extracellular matrix (ECM) significantly decreased in the rhein group after the full treatment course, but not in the simvastatin group. The more powerful effects of rhein on decreasing transforming growth factor-beta1 (TGF-beta1) and fibronectin immunohistochemistry expression in renal tissue were also observed. And the plasma levels of cholesterol (Chol), triglyceride (TG), low-density lipoprotein cholesterol (LDL-C) and ApoE all decreased in both the rhein and the simvastatin groups. Together, our data suggested that both rhein and simvastatin regulate dyslipidemia. The powerful effect of rhein in renal protection is due to its widespread effects. Rhein is a new drug that can decrease lipid levels and protect against DN progression in a different fashion with simvastatin.

Evaluation of podocyte lesion in patients with diabetic nephropathy: Wilms' tumor-1 protein used as a podocyte marker.

INTRODUCTION: The reduction of podocyte number and density per glomerulus has been linked to the development of proteinuria and the progression of disease in patients with diabetic nephropathy (DN). However, it has been recognized that measurement of podocyte number by light microscope is quite difficult because of the complexity of both podocyte and glomerular structure, which is not suitable for clinical research. In our research institute, we used WT1 as podocyte marker to evaluate the podocyte lesion. METHODS: In our experiment, we selected the C-terminal antibody of WT1 to stain the nuclei and the N-terminal antibody of WT1 to stain the cytoplasma of podocytes. Forty patients were enrolled with type 2 diabetes and proven to have DN by renal biopsy analysis. DN patients were classified into three groups based on the degree of proteinuria: microalbuminuria (n=10, 30-300mg/24h), overt proteinuria (n=15, 0.5-3.5g/24h), and heavy proteinuria (n=15, >3.5g/24h). RESULTS: The results demonstrated that the podocyte number was markedly decreased in patients with DN (30-51% reduction). There was a significant negative correlation between the proteinuria and both podocyte density and number. The cover area density of podocyte cytoplasma in glomerulus was also significantly decreased in all DN patients (39-80% reduction). A significant inverse correlation was observed between the cover area density and the degree of proteinuria. The correlation coefficient (r=-0.85) was much higher than that between proteinuria and podocyte density (r=-0.56) or podocyte number (r=-0.36). CONCLUSION: In conclusion, podocyte damage occurred in patients with DN, even in the early stage and became more dramatic during the course of proteinuria progression. WT1 staining, using the polyclonal antibody to stain the nuclei and monoclonal antibody to stain the cytoplasma of podocytes together, is a valuable alternative technique in the study of podocyte injury.

Ultrastructural changes in the glomerular filtration barrier and occurrence of proteinuria in Chinese patients with type 2 diabetic nephropathy.

AIM: Diabetic nephropathy (DN) is one of the most important causes of end stage renal disease in the world. Its hallmark is proteinuria. Therefore, we set out to clarify the structural changes that occur in the glomerular filtration barrier in Chinese patients with true type 2 diabetic nephropathy, and to examine the relationship between these structural changes and proteinuria. METHODS: 42 Chinese patients with true T2DN were divided into three groups according to urinary protein excretion. Glomerular volume, endothelial cell density, endothelial cell number, glomerular basement membrane (GBM) width, podocyte density, podocyte number and foot process width were evaluated using light and electron microscopic morphometry. RESULT: Glomerular volume and endothelial cell number were increased in diabetic patients, but there was no difference between patients with respect to the degree of proteinuria. As proteinuria progressed, endothelial cell density remained unchanged, while the glomerular basement membrane (GBM) and podocyte foot process width increased, podocyte density and number decreased. CONCLUSIONS: Podocyte and GBM change more obviously during the development of proteinuria. Besides, proteinuria was inversely related to podocyte density, and directly related to GBM and glomerular volume.

Presence of foam cells in kidney interstitium is associated with progression of renal injury in patients with glomerular diseases.

BACKGROUND: Renal interstitial foam cells (FCs) are occasionally observed in various renal diseases. The goal of the present study was to determine the relationship between the formation of renal interstitial FCs and the degree of proteinuria and hyperlipidemia, as well as the progression of these diseases. METHODS: 125 patients with Alport syndrome (AS), 192 patients with idiopathic membranous nephropathy (IMN), 388 patients with IgA nephropathy (IgAN), and 137 patients with focal segmental glomerulosclerosis (FSGS) were investigated retrospectively. RESULTS: FCs were observed in various glomerular diseases. The frequency of interstitial FCs was 64.8% in AS, 21.4% in MN, 12.4% in IgAN, and 36.5% in FSGS. Regardless of the pathologic diagnosis of the glomerular disease, segmental glomerular sclerosis occurred more frequently in patients with FCs than in patients without FCs. In the AS or IgAN group, interstitial fibrosis was more severe, and levels of proteinuria and serum lipids were significantly higher in FC-positive patients than in patients without FCs. CONCLUSION: FC formation in renal interstitium is associated with the degree of proteinuria and hyperlipidemia in patients with AS and IgAN. The presence of FCs in renal interstitium may contribute to the progression of glomerular diseases.

The Oxford classification of IgA nephropathy: pathology definitions, correlations, and reproducibility.

Pathological classifications in current use for the assessment of glomerular disease have been typically opinion-based and built on the expert assumptions of renal pathologists about lesions historically thought to be relevant to prognosis. Here we develop a unique approach for the pathological classification of a glomerular disease, IgA nephropathy, in which renal pathologists first undertook extensive iterative work to define pathologic variables with acceptable inter-observer reproducibility. Where groups of such features closely correlated, variables were further selected on the basis of least susceptibility to sampling error and ease of scoring in routine practice. This process identified six pathologic variables that could then be used to interrogate prognostic significance independent of the clinical data in IgA nephropathy (described in the accompanying article). These variables were (1) mesangial cellularity score; percentage of glomeruli showing (2) segmental sclerosis, (3) endocapillary hypercellularity, or (4) cellular/fibrocellular crescents; (5) percentage of interstitial fibrosis/tubular atrophy; and finally (6) arteriosclerosis score. Results for interobserver reproducibility of individual pathological features are likely applicable to other glomerulonephritides, but it is not known if the correlations between variables depend on the specific type of glomerular pathobiology. Variables identified in this study withstood rigorous pathology review and statistical testing and we recommend that they become a necessary part of pathology reports for IgA nephropathy. Our methodology, translating a strong evidence-based dataset into a working format, is a model for developing classifications of other types of renal disease.

The Oxford classification of IgA nephropathy: rationale, clinicopathological correlations, and classification.

IgA nephropathy is the most common glomerular disease worldwide, yet there is no international consensus for its pathological or clinical classification. Here a new classification for IgA nephropathy is presented by an international consensus working group. The goal of this new system was to identify specific pathological features that more accurately predict risk of progression of renal disease in IgA nephropathy, thus enabling both clinicians and pathologists to improve individual patient prognostication. In a retrospective analysis, sequential clinical data were obtained on 265 adults and children with IgA nephropathy who were followed for a median of 5 years. Renal biopsies from all patients were scored by pathologists blinded to the clinical data for pathological variables identified as reproducible by an iterative process. Four of these variables: (1) the mesangial hypercellularity score, (2) segmental glomerulosclerosis, (3) endocapillary hypercellularity, and (4) tubular atrophy/interstitial fibrosis were subsequently shown to have independent value in predicting renal outcome. These specific pathological features withstood rigorous statistical analysis even after taking into account all clinical indicators available at the time of biopsy as well as during follow-up. The features have prognostic significance and we recommended they be taken into account for predicting outcome independent of the clinical features both at the time of presentation and during follow-up. The value of crescents was not addressed due to their low prevalence in the enrolled cohort.

Clinical features and renal outcome in lupus patients with diffuse crescentic glomerulonephritis.

The objectives of the study are to investigate the clinical features and renal outcomes in lupus patients with diffuse crescentic glomerulonephritis (DCGN). Ninety-four DCGN lupus patients were enrolled. Their clinical features and renal outcomes were investigated. There were 84 females and 10 males, with a mean age of 27.9 ± 10.7 years old. They represented: hypertension in 73 cases (77.7%), rapidly progressive glomerulonephritis in 62 cases (66.0%), 46 cases (48.9%) with nephritic syndrome, 35 (37.2%) gross hematuria, and 14 cases (14.9%) with uremic syndrome needed dialysis therapy. There were 25 cases received repeated renal biopsy. Their histological examination showed the decreasing of active lesions and the increasing chronic lesions. All patients were more than 6 months follow-up, and 79 patients (84.0%) were more than 12 months follow-up. At the first time of follow-up (3 months), the renal function, proteinuria, and anemia were improved significantly in all of cases received intensive immunosuppressive therapy. At the last time of follow-up (56.1 ± 18.8 months), only four patients eventually developed to the end-stage renal failure and five died with normal renal function. The lupus patients with DCGN presented more severe clinical syndromes, which were similar to those patients of type II of DCGN. The relative good renal outcomes were observed in those lupus patients, to which may be contribute to the effective induction therapy.

Mycophenolate mofetil versus cyclophosphamide for induction treatment of lupus nephritis.

Recent studies have suggested that mycophenolate mofetil (MMF) may offer advantages over intravenous cyclophosphamide (IVC) for the treatment of lupus nephritis, but these therapies have not been compared in an international randomized, controlled trial. Here, we report the comparison of MMF and IVC as induction treatment for active lupus nephritis in a multinational, two-phase (induction and maintenance) study. We randomly assigned 370 patients with classes III through V lupus nephritis to open-label MMF (target dosage 3 g/d) or IVC (0.5 to 1.0 g/m(2) in monthly pulses) in a 24-wk induction study. Both groups received prednisone, tapered from a maximum starting dosage of 60 mg/d. The primary end point was a prespecified decrease in urine protein/creatinine ratio and stabilization or improvement in serum creatinine. Secondary end points included complete renal remission, systemic disease activity and damage, and safety. Overall, we did not detect a significantly different response rate between the two groups: 104 (56.2%) of 185 patients responded to MMF compared with 98 (53.0%) of 185 to IVC. Secondary end points were also similar between treatment groups. There were nine deaths in the MMF group and five in the IVC group. We did not detect significant differences between the MMF and IVC groups with regard to rates of adverse events, serious adverse events, or infections. Although most patients in both treatment groups experienced clinical improvement, the study did not meet its primary objective of showing that MMF was superior to IVC as induction treatment for lupus nephritis.

Diagnosis, pathogenesis, treatment, and prognosis of hereditary fibrinogen A alpha-chain amyloidosis.

Mutations in the fibrinogen A alpha-chain gene are the most common cause of hereditary renal amyloidosis in the United Kingdom. Previous reports of fibrinogen A alpha-chain amyloidosis have been in isolated kindreds, usually in the context of a novel amyloidogenic mutation. Here, we describe 71 patients with fibrinogen amyloidosis, who were prospectively studied at the UK National Amyloidosis Centre. Median age at presentation was 58 yr, and renal involvement led to diagnosis in all cases. Even after a median follow-up of 4 yr, clinically significant extra-renal disease was rare. Renal histology was characteristic: striking glomerular enlargement with almost complete obliteration of the normal architecture by amyloid deposition and little or no vascular or interstitial amyloid. We discovered four amyloidogenic mutations in fibrinogen (P552H, E540V, T538K, and T525fs). A family history of renal disease was frequently absent. Median time from presentation to ESRD was 4.6 yr, and the estimated median patient survival from presentation was 15.2 yr. Among 44 patients who reached ESRD, median survival was 9.3 yr. Twelve renal transplants survived for a median of 6.0 (0-12.2) yr. Seven grafts had failed after median follow up from transplantation of 5.8 yr, including three from recurrent amyloid after 5.8, 6.0, and 7.4 yr; three grafts failed immediately for surgical reasons and one failed from transplant glomerulopathy after 5.8 yr with no histological evidence of amyloid. At censor, the longest surviving graft was 12.2 yr. In summary, fibrinogen amyloidosis is predominantly a renal disease characterized by variable penetrance, distinctive histological appearance, proteinuria, and progressive renal impairment. Survival is markedly better than observed with systemic AL amyloidosis, and outcomes with renal replacement therapy are comparable to those for age-matched individuals with nondiabetic renal disease.

Effects of mycophenolate mofetil for patients with crescentic lupus nephritis.

OBJECTIVE: To compare the effects, relapse ratio and outcomes between mycophenolate mofetil (MMF) and pulse intravenous cyclophosphamide (CTX) for the induction therapy in patients with crescentic lupus nephritis. METHODOLOGY: This is a retrospective, controlled study. Twenty-seven MMF therapeutic and twenty-five CTX therapeutic lupus patients with >or=50% crescent formation were enrolled in this study. The general conditions, clinicopathological findings, remission and relapse ratio, and outcomes of them were compared. RESULTS: There was no significant difference of general condition and clinicopathological findings between MMF and CTX group. At 12 months, the total remission ratio in MMF and CTX group were 73.1% and 69.6%, while the complete remission ratio in MMF group (53.8%) was significantly higher than that in CTX group (26.1%). The relapse ratio in MMF group (10.5%) was significantly lower than in CTX group (43.8%). Forty per cent of PR patients in CTX group suffered from relapse. Until June 2005, the patients in CTX group received a follow time with 38.5 +/- 21.2 (range 10 approximately 80) months, and in MMF group the follow time was 41.1 +/- 27.0 (range 12 approximately 90) months. Two patients in MMF group and two in CTX group entered into end stage renal failure. The side effect of infection was more significant in CTX group. CONCLUSION: Higher complete remission ratio and lower relapse ratio were observed in MMF group than in CTX group. The side effect of infection was more infrequent in MMF group, which showed preferable security of MMF.