Objective: To investigate the clinical and pathological features of complement C3 (C3) glomerulonephropathy. Methodology: 17 Chinese patients diagnosed with C3 glomerulonephropathy by clinical and histopathological methods (light microscopy, immunofluorescence and electron microscopy ) were enrolled. The clinical data and pathologic features of 17 patients were analyzed. Results: There were 11 males and 6 females with average age of 34.1±19.1 years (10~75) and renal history 1.3±1.2 years (1week~8 years）. Most patients had no obvious predisposing causes. The initial symptoms were edema and proteinuria in most patients. Among which, 5 had nephritic syndrome and 3 had rapidly progressive glomerulonephropathy. Urinary analysis showed proteinuria of 3.1±3.2g/d with micro-hematuria (64.7%) ( including 5 gross hematuria).  Hypertension were found in 10 cases and elevated serum creatinine in 4. There were 11 patients with low complement C3 and 5 with anemia. C3 nephritic factor (C3NF) were carried out in 5 cases，only 1 patients were positive. Renal biopsy revealed membrane proliferative glomerulonephritis (MPGN) in 12 patients（70.6%）with endothelial and mesangial proliferative, some with thickened glomerular basement membrane (GBM). Granular C3 were deposited along with GBM，but absence of substantial immunoglobulin by immunofluorescence (IF). Electron microscopy observation found the presence of subendothelial and mesangial electron-dense deposits. There were 15 patients followed-up for 1 month to 5 years，2 was complete remission and 11 had partial remission with immunosuppressive therapy. Conclusion: C3 glomerulonephropathy was newly recognized in recent years. There was no significant  clinical features of  this disease. Immunofluorescence evidence showed C3 predominantly deposited within the GBM. Electron microscopy was valuable in the diagnosis. There was no effective treatment of C3 glomerulonephropathy. Further investigation of mechanism is needed.

ABSTRACT  Objective: To investigate the metabolomic profile in serum and urine of patients with DN at different stages, and find out biomarkers for early diagnosis and prognosis of DN. Methodology: Ninety male patients diagnosed as type 2 diabetic mellitus (T2DM) were enrolled this study. They were divided into 3 groups (normoalbuminuria, n=30, microalbuminuria, n=30, and proteinuria, n=30). Twenty-five health controls were included. Serum and urine metabolites were analyzed using gas chromatography/mass spectrometry (GC/MS) and liquid chromatography/mass spectrometry (LC/MS).  Results: Distinct metabolomic differences were observed between different stages of DN. All the three groups of patients showed clear dysfunction of glycolysis and tricarboxylic acid cycle. Activation of protein kinase C pathway and hexosamine biosythesis pathway were also demonstrated. The levels of serum branched-chain amino acids were increased in the diseased group. The levels of serum non-essential fatty acid were elevated, while L-cartinine and acyl CoA were decreased, which indicated the dysfunction of β-oxidation of fatty acids. The palmitic acid in the serum, as well as PC (P-19:1(12Z)/0:1) and dodecanedioic acid in the urine might be candidate biomarker for early diagnosis of DN. Decanoyl-L-carnitine, PC (9:0/0:0) and Dg (17:2(9Z,12Z)/20:3 (8Z,11Z,14Z)/0:0) in the serum, as well as uridine diphosphate and lysoPC (16:0) might be candidate biomarkers for prognosis of DN. Conclusion: Our study demonstrated the changes of metabolic profile in different stages of DN, and provided candidate biomarkers for early diagnosis and prognosis.

Objective: To investigate the clinicopathological features and prednisone therapeutic effect of IgA nephropathy with minimal change lesion. Methodology: Sixty one patients[46 male and 15 female with average age of（23.9±8.65）years old] ，who were biopsy-based IgA nephropathy with the minimal change lesion，were enrolled in this retrospective study. Their clinical manifestations, pathological features and prednisone therapeutic effect were analyzed. Results: Nephrotic syndrome was the primary clinical manifestation. All patients presented severe proteinuria and edema, 15 cases（24.6%）had infections as a motivation, 14 cases（23.0%）showed AKI, 14 cases（23.0%）had microhematuria and 5 cases（8.2%）presented with hypertention. The increasing levels of urine n-acetyglucosaminidase（NAG）（78.7%）and urine retinol binding protein（RBP）（75.4%）were seen in a majority. The histological examinations showed that the glomerular lesion was minimal, and immuneglobulin A alone（14.3%）or togethter with immuneglobulin M (61.9%）were mostly seen in the mesangial region. The renal tubules and interstitial tissues obviously got acute injury with a proportion of 80.3% and 65.6% respectively. During the follow-up of 46 months（24~70）, the effective and relapse rate of prednisone therapy were 91.8% and 76.8%. Compared to responders, the nonresponders got a higher incidence and severity of hematuria（P<0.01）and the hypoproteinemia was not as obvious as the former（P<0.05）.Besides,tubular atrophy，interstitial fibrosis and hyaline degenetantion of arteriole appeared more often in nonresponders（P<0.01）.Till the last follow-up,59 cases（96.7%）still had nomal renal funtion.Conclusion:IgA nephropathy with minimal change like lesion were similar with minimal change desease both in clinical menifestation and pathological feature.Most cases got remission with prednisone therapy,and they usually showed good prognosis .

Objective：To study the different clinical parameters of bone metabolism between hemodialysis and hemofiltration patients.  Methodology: Thirty uremic patients with maintenance hemodialysis were randomly divided into hemodialysis group (HD group, n = 15) and hemodiafiltration group (HDF group, n = 15), 15 cases of healthy persons as control group. After 10 months of dialysis, the levels of serum osteocalcin (BGP), β-I collagen C-terminal peptide (β-CTX), I procollagen amino-terminal propeptide (PINP), and parathyroid hormone (PTH) levels and changes were compared between two groups before and after dialysis. Results: All patients showed increased baseline mean values of BGP, β-CTX, PINP, and PTH (P<0.001). In HD group, all these bone metabolism markers were higher than that in HDF group (P<0.05).  The levels of serum BGP, β-CTX were decreased significantly after a single HD (P<0.05), but serum PTH was no significant difference. In HDF Group, the levels of serum BGP, β-CTX, PTH were significantly reduced at the end of the session (P<0.01), and declined more than that in HD group. However, the levels of serum PINP did not change significantly in both groups.  Conclusion: Hemodiafiltration might decrease bone turnover, and improve renal osteodystrophy in patients with maintenance hemodialysis, especially for high-turnover renal osteodystrophy.

ABSTRACT   objective: To evaluate the predictive power of the pathologic classification in type 2 diabetes mellitus (T2DM).  Methodology:  Four hundred and fourteen T2DM patients who had biopsy-confirmed DN and followed for at least a year after biopsy from January 2003 to November 2011 at Jinling Hospital were enrolled in this retrospective study. The relevancies between pathological findings and renal outcome were assessed. All cases were categorized according to the pathologic classification of Tervaert having reported. Some common pathological changes of DN were also examined. A renal event was defined as eGFR<15 ml/(min.1.73m2).   Results: They were 260 male and 154 female with an average age of 50.0±9.10 years old. Among them, there were 63 in Class I, 95 Class IIa , 32 Class IIb , 168 Class III, and 56 Class IV. The 5-year renal survival rates were 100%, 90%, 75%, 39% and 15%, respectively. Cox regression showed that the glomerular classes, interstitial fibrosis and tubular atrophy (IFTA) and interstitial inflammation can significantly influence renal survival in these patients. Scores of arteriolar hyalinosis and arteriosclerosis were not significant variables. More than one area of arteriolar hyalinosis was commonly found in 95.4% of these patients, indicating that this index may not be suitable for classification. The patient with nodule lesions, glomerular microaneurysms, atubular glomeruli, segmental sclerosis, hyaline caps, fibrinoid exudation, foam cells within loops, glomerular inflammation, crescents, and segmental endothelial proliferation had a worse renal survival. Multivariate COX analysis showed that the glomerular classes, IFTA and acute tubular injury were independent risk factors for renal prognosis, even when adjusted for proteinuria, blood pressure and eGFR. Conclusion: The glomerular classification and IFTA are significantly associated with renal outcome in patients with T2DM, independently of proteinuria, blood pressure and eGFR. However, the vascular indexes in the classification are incapable to reflect the difference in vascular lesion severity of the patients and can’t be used for renal prognosis, suggesting a necessity to redefine them.

Objective: To analyze the current situation of peritoneal dialysis in our country and the factors influencing the long-term prognosis by review of single peritoneal dialysis center registration data system.  Methodology:Patients on maintenance PD were retrospectively studied from January 2002 to December 2010. The Kaplan–Meier method for measuring patient survival rate and technique survival rate were applied. We also analyzed the risk factors and calculated their hazard ratio (HR) for patient mortality and PD technique failure using multivariate regression of the Cox proportional hazards method.   Results：A total of 681 patients were recruited. Among them, 398 (58.5%) were males, and the mean age at the start of PD was 45.7±16.4 years old, Chronic glomerulonephritis（CGN）was the main cause of end stage renal disease（ESRD）, and followed by diabetes mellitus (11.8%). Mean PD duration was 13.9±16.4 months. There were 604 cases (88.7%) receiving day ambulatory peritoneal dialysis (DAPD), while 77 (11.3%) got continuous ambulatory peritoneal dialysis (CAPD). The 1, 3, 5 and 8 years of technical survival rates were 87.0%, 74.4%, 61.8% and 53.0%, respectively. While the 1, 3, 5 and 8 years of patient survival rates were 94.8%, 78.9%, 70.6% and 48.5%, respectively.Excluded patients giving up treatment due to economic factors，the causes of quit PD were cardiovascular diseases (23%~41%), dialysis inadequacy (25%~43%)，peritonitis (10%~16.7%).catheters complications(6.7%-10.3%) and pleural effusion (0-6.7%).The main causes of death were cardiovascular events (23%~41%), cerebrovascular events (12.5%~20%) and infection (6.3%~15.4%).The predictors of patient drop-out in our study were anemia [relative risk (RR) 0.53, p < 0.01], protein energy malnutrition (RR 0.77, p < 0.05),low serum albumin level (RR 9.49, p < 0.01) upon starting PD.  Conclusion：The patients with PD in our center had a good technical survival rate. The main factor influencing the prognosis was cardiovascular diseases and dialysis inadequacy.

A 31-year old man presented with exercise induced acute renal failure. He experienced oliguria, myalgia, hyperkalemia, elevation of blood creatine kinase, myoglobinuria and dark urine. Renal biopsy revealed mild brown granular casts and acute tubular injury. Myoglobin casts and myoglobin deposits in tubular epithelial cells were conformed by immunohistochemistry. The diagnosis of exertional rhabdomyolysis and myoglobinuria induced acute kidney injury was made.

Objective: The aim of this study is to explore the application of heat antigen retrieval combined with pepsin digestion on immunofluorescence (IF) staining for paraffin embedded human renal tissues. Methodology: Renal-biopsy proved 9 groups of glomerular diseases from Research Institute of Nephrology, Jinling Hospital were enrolled, they were membranous nephropathy (n=6), membranoproliferative glomerulonephritis (n=5), lupus nephritis including class IV(n=2) and class IV+V(n＝2), IgA nephropathy(n =12), anti-GBM disease(n=4)，dense deposit disease（n=4）, acute poststreptococcal glomerulonephritis (n=6), light-chain deposition disease (kappa) (n=4), and primary amyloid (lambda) (n=4). Paraffin -embedded sections of renal biopsy tissues were processed by using heat antigen retrieval with pressure cooke (EDTA, pH=8.0) combined with pepsin digestion and immunofluorescence staining of IgG, IgA, IgM, C3, C1q, κ、λ light chain. And then we compare the immunofluoresence staining of frozen sections (IF-F) with heat antigen retrieval combined with pepsin digestion paraffin-embedded sections (IF-P). Results: IF-P of IgG , IgA, and C1q, was in accordance with that of frozen sections in positive rate, distribution pattern and staining intensity. IF-P of IgM and C3 was the same with IF-F in distribution pattern. However, the intensity and positive rate was inferior to IF-F, which was not influent on diagnosis. One hundred percent of diagnostic accordance rate was obtained in IF-P. Furthermore, the structure of paraffin sections were clearer than that of frozen sections, which led to more easier judgment of the location of immunecomplex deposits. Conclusion: IF-P is a good alternative for immunofluoresence staining in the condition of frozen tissues without glomerula. This method is useful for retrospective study on paraffin-embedded sections of renal biopsy tissues.

Objectives: To iinvestigate the long-term renal survival rate and related risk factors of progression to renal failure in Chinese adult patients with IgA nephropathy (IgAN) and to quantify the effects of proteinuria during the follow-up on outcome in patients with IgAN. Methodology: The patients with biopsy-proven primary IgAN in the Nanjing Glomerulonephritis Registry were studied. Renal survival and the relationships between clinical parameters and renal outcomes were assessed. Results: 1126 patients were enrolled in this study. The 10, 15, and 20-year cumulative renal survival rates, calculated by Kaplan-Meier method, were 85%, 76% and 67% respectively. At the time of biopsy, proteinuria>1.0g/d (HR 3.3，P<0.001), eGFR<60 ml/min per 1.73m2 (HR 2.2，P<0.001), hypertension (HR 2.0，P<0.001), and hyperuricemia (HR 1.8，P=0.002) were the independent risk factors. Multivariate COX analysis showed the time-average proteinuria (TA-P) during follow-up was the most important risk factor of renal failure. The patients with TA-P>1.0g/d were associated with a 9.8-fold risk than that patients with TA-P<1.0g/d (P<0.001), and 67.7-fold risk than those with TA-P<0.5g/d (P<0.001). The patients with TA-P<0.5g/d were better than those with TA-P between 0.5 and 1.0g/d (HR 13.1, P<0.001). Conclusions: 33% of Chinese adult patients with primary IgAN have progressed to End Stage Renal Disease (ESRD) within 20 years. Four clinical features--higher proteinuria, hypertension, impaired renal function, and hyperuricemia are independent predictors of an unfavorable renal outcome. The basic goal of antiproteinuric therapy for Chinese patients is to lower proteinuria to <1.0g/d, and the optimal goal is to lower proteinuria to <0.5g/d.

 Objective: To investigate the long-term renal outcome and prognostic factors of adult endocapillary proliferative glomerulonephritis.  Methodology: A total of 62 adult patients, who diagnosed as endocapillary proliferative glomerulonephritis by renal biopsy, were enrolled in this study. They were divided into two groups: streptococcal group (n=43) and non-streptococcal group (n=19). The clinical and pathological features were summarized. For the purpose of outcome analysis, 47 patients with a follow-up of ≥12 months were included. The univariate and multivariate analyses were performed for prognostic factors.  Results: Proteinuria and hematuria were both more severe in non-streptococcal group. There were no significant differences on light microscopy between 2 groups. Among the 47 patients with ≥ 12 months of follow-up, the complete remission rate was 89.4% and the incidences of chronic renal failure and ESRD were 4.3% and 2.1%. The univariate analysis showed that the prognostic factors were age, underlying disease, tubular damage and C1q staining respectively. On multivariate analysis, underlying disease and proteinuria were significant and independent inverse correlate of complete remission.  Conclusion: The long-term prognosis of adult endocapillary proliferative glomerulonephritis is optimistic. Proteinuria and underlying disease are important prognostic factors.

Objective: To develop a method for glomerular purification that can further perform the molecular biology for nephrology research.  Medthodology: After the anesthetization, the thorax and abdomen cavity of the mouse was opened.  Iron oxide solution was microperfused into the microvascular circulation of the whole body that include kidneys. Kidneys were dissected and minced into small pieces, then digested with collagenase A in PBS. The tissue was diluted in PBS and gently pressed through a filter followed by rinsing with PBS. Glomeruli that contained iron oxide were isolated with a magnetic particle concentrator and washed with PBS. Electron microscope was used for the observation of glomerular morphology. Extracted total RNA and protein from isolated glomeruli were further employed for quantitative Real-Time polymerase Chain Reaction (qRT-PCR), miroRNA microarray and Western blotting experiments.  Results: We developed a method that allows largely and quickly to purify the glomerulus at different developing/developed stage from postnatal day 1 to adult mice. The structure and ultrastructure of glomerulus purified were entirely kept and normal under the electro-microscope. The total RNA and protein extracted from the glomerulus purified were successfully used to the molecular biological research, including qRT-PCR, Western blotting and microRNA microarray.  Conclusion: This method is simple and cheaper to purify the glomerulus, which provides a useful and powerful tool for basic science and clinic research relevant to nephrology.

Objective: To prospectively observe the clinical efficacy and safety of Corticosteroids in combination with mycophenolate mofetil dispersible tablets (Cicopin○R,MMF, Hangzhou Zhongmei Huadong pharmaceutical Co, Ltd) and tacrolimus (FK506, Hangzhou Zhongmei Huadong pharmaceutical Co, Ltd) (multi-target group) in the induction treatment for lupus nephritis (LN).  Methodology: Seventy-nine patients with biopsy confirmed class IV, V + IV and V + III LN were randomly assigned to either multi-target group (n= 45, 39 females, 6 males, mean age 25.1±9.3 years) or intravenous cyclophosphamide pulse therapy(IV-CYC)(n = 34, 30 females, 4 males, mean age 30.4 ± 8.9 years). All patients received intravenous methylprednisolone pulse therapy followed by oral prednisone. In multi-target group, the dose of MMF and FK506 was adjusted based on the blood level with the MPA-AUC0 ~ 12h level of 20-30 mg • h /L and FK506 trough level 4-7ng/ml. In IV-CYC group, CYC was given in a dose 0.5-0.75g/m2BSA monthly. The induction period was 6months or 9 months according the responses to the therapy. Primary efficacy parameter was complete remission rate (defined as urine protein <0.4g/24h, serum albumin ≥ 35g/l, normal serum creatinine and no extra-renal activity), the secondary parameters were partial remission rate (defined as urinary protein than the base value reduced by 50% or more, and urine protein <3.5g/24h, serum albumin ≥ 30g/l, serum creatinine stable) and incidence of adverse reactions. The clinical efficacy and adverse events were compared between two groups.  Results: The baseline clinical and histological classes had no siginificant differences between multi-target group and IV-CYC group. The accumulated complete remission rate of multi-target group was significantly higher than IV-CYC group (P <0.05) during the induction period. At 6months and 9 months, the complete remission rate was 53.3% and 62.2% respectively in the multi-target group, and 29.4% and 42.6%, in IV-CYC group respectively. Also, Multi-target therapy showed much higher complete remission rate  than IV-CYC therapy for class V+IV (50.0% vs 16.7%, P<0.05) and class V + III(54.5% vs 22.2 %, P> 0.05). In class IV LN, no difference of the remission rate was found between the two groups. The incidence of adverse events in the multi-target group was much lower than that in the IV-CYC group (31.1% vs 70.6%, P <0.01), the major adverse events were new-onset hypertension (11.1%) and herpes zoster (6.7%) in the multi-target group, gastrointestinal reactions (23.5%), leukopenia (13.7%) and skin infections (8.8%) in the IV-CYC group. Three patients( 2 in multi-target group and 1 in IV-CYC group) complicated with pulmonary infection, none died.  Conclusion: The multi-target therapy, which is composed of corticosteroids with Cicopin and tacrolimus, showed more effective than intravenous CYC pulse therapy in inducing remission of lupus nephritis, especially class V+IV, and had a more favorable safety. Howere, multi-center clinical trials are encouraged to evaluate the clinical efficacy and the impact on long-term survival for lupus nephritis.

ABSTRACT  Objective: The endogenous glucocorticoids (GC) is required for activation of muscle protein degradation in chronic kidney disease (CKD) related protein energy wasting. We studied the muscle wasting in a muscle specific glucocorticoids receptor knockout mouse (MGRKO) with CKD model. We hypothesis the MGRKO could suppress muscle atrophy. Methodology: MGRKO and lox/lox mice CKD model was made by 5/6 nephroctomy, and the sham was regarded as control (CTL). The serum corticosteroid hormone was measured by ELISA. The bodyweight and Tibia Anterior (TA) muscle weight were measured. The TA muscle size of was observed under microscope and calculated with software. The expression of Atrogin-1（Muscle Atrophy Fbox-1）and MuRF-1 (Muscle RING finger 1) was measured by Q-PCR and western blot. We also analyzed the signaling pathway of Akt/FoxO1. Results: The levels of serum BUN and corticosteroids were increased dramatically in lox/lox-CKD and MGRKO-CKD, but no differences between two groups. The bodyweight and TA muscle weight in the lox/lox-CKD was lower than that in the lox/lox- CTL L; but no difference between the MGKO-CTL and MGKO-CKD. The cross-sectional area of muscle fibers in the MGRKO-CKD was smaller, and the shrinkages of fibers sizes caused leftward shift in fiber size distribution was obvious in lox/lox-CKD, but only mild change in MGRKO+CKD mice’s muscle. The level of Atrogin-1 and MuRF-1 was increased dramatically, and the Akt/FoxO1 signaling pathway was abnormal which showed the level of phosphorylated Akt/FoxO1 repressive simultaneously in lox/lox-CKD (p<0.001). Whereas, the Atrogin-1 mRNA showed a mild higher (p<0.05), the MuRF-1 mRNA showed no difference, and the Akt/FoxO1 signaling abnormal was unconspicuous in the MGKO-CKD, which showed suppresses insulin/IGF-1 stimulation of Akt/FoxO1 activities. The MGRKO could resist to this abnormal, hence, ameliorate CKD induced muscle wasting. Conclusion: Endogenous Glucocorticoids (GC) may play an important role in CKD induced muscle wasting, muscle specific GC receptor knockout( MGRKO) can be resistant to muscle atrophy and loss of bodyweight induced by CKD. The mechanism might be MGRKO arrest the GC suppressing insulin/IGF-1 stimulation of Akt/FoxO1 activities, then, stop the active of Atrogin-1 and MuFR-1.

The activation of the renin–angiotensin–aldosterone system (RAAS) may play an important role on the morphological changes of the peritoneal membrane. This brief review will describe our current state of knowledge about the role of RAAS in peritoneal membrane damage and potential strategies to protect the membrane.

 Glomerular filtration rate (GFR) is an important index for evaluating kidney function, and also the important basis to classify for the chronic kidney disease (CKD). The equations for evaluating GFR are simple and can be widely used, which are CG（Cockcroft-Gault） equation , MDRD（Modification of Diet in Renal Disease）equation, CKD-EPI,modified MDRD equation, ruijin equation and cystatin equation. The aim of this review is to look for which equation is better to evaluate GFR. Through comparing their bias, precision, accuracy and other indices, which one is much better can determined. As a result, CG equation is better used in healthy people, but it is worse used in those who have kidney disease and it is affected by weight evidently. MDRD equation is better used in those of kidney disease, but it is worse used when GFR is high. CKD-EPI overcomes this disadvantage. Modified MDRD equation and ruijin equation are better used in Chinese people. Cystatin equation is better used in the early stage of kidney disease. No equation is perfect. So these equations need to be improved deeply or need to develop better equations to evaluate GFR.

The serum levels of 25-hydroxyvitamin D insufficiency or deficiency remains common in most individuals with end-stage renal disease (ESRD). However, it is still argued that which kind of vitamin D analogues-active vitamin D or nutritional vitamin D, is used for treatment. Kidney Disease Outcome Quality Initiative (K/DOQI) guideline suggests that nutritional vitamin D(NVD) is initiated to treat nondialysis chronic kidney disease (CKD) patients with secondary hyperparathyroidism for low levels of 25-hydroxyvitamin D (<30ng/ml).Though some small sample studies, which exist significant defects on design or implementation of clinical trials, showed that nutritional vitamin D can decrease levels of parathyroid hormone, and improve sensitivity to erythropoietin stimulating agents and glycemic, nutritional vitamin D is not proved to improve survival. In contrast, active vitamin D can exert significant survival advantage on reducing mortality of CKD patients and increased biochemical marker-alkaline phosphatase, with coronary artery calcification.