Honglang Xie

Successful Treatment of Class V+IV Lupus Nephritis with Multitarget Therapy

Treatment of class V+IV lupus nephritis remains unsatisfactory despite the progress made in the treatment of diffuse proliferative lupus nephritis. In this prospective study, 40 patients with class V+IV lupus nephritis were randomly assigned to induction therapy with mycophenolate mofetil, tacrolimus, and steroids (multitarget therapy) or intravenous cyclophosphamide (IVCY). Patients were treated for 6 mo unless complete remission was not achieved, in which case treatment was extended to 9 mo. An intention-to-treat analysis revealed a higher rate of complete remission with multitarget therapy at both 6 and 9 mo (50 and 65%, respectively) than with IVCY (5 and 15%, respectively). At 6 mo, eight (40%) patients in each group experienced partial remission, and at 9 mo, six (30%) patients receiving multitarget therapy and eight (40%) patients receiving IVCY experienced partial remission. There were no deaths during this study. Most adverse events were less frequent in the multitarget therapy group. Calcineurin inhibitor nephrotoxicity was not observed, but three patients developed new-onset hypertension with multitarget therapy. In conclusion, multitarget therapy is superior to IVCY for inducing complete remission of class V+IV lupus nephritis and is well tolerated.

The spectrum of biopsy-proven kidney diseases in elderly Chinese patients

BACKGROUND Studies on biopsy-proven renal disease in the elderly (age ≥65 years) are extremely limited in China. The aim of this study was to examine the spectrum of renal diseases and their clinical presentations in elderly patients undergoing renal biopsy. METHODS All native renal biopsies (n = 851) performed in patients aged ≥65 years from January 2003 to December 2012 were retrospectively analyzed. The results were compared with a control group of 28 574 patients aged 18-64 years undergoing renal biopsy over the same period. RESULTS These 851 patients included 549 males and 302 females. Primary glomerular diseases (53.94%) occurred more frequently than secondary glomerular diseases (36.49%). The clinical manifestations were nephrotic syndrome (NS) in 29.49% of the patients, chronic renal failure in 24.68%, proteinuria and hematuria in 13.28%, proteinuria in 10.93%, acute kidney injury (AKI) in 10.81% and AKI and NS in 8.93%. Membranous nephropathy (MN) was the most frequent diagnosis (28.79%), followed by diabetic nephropathy (DN, 9.75%), IgA nephropathy (IgAN, 9.64%) and vasculitis (6.82%). When compared with the control group, the results showed that MN (P < 0.0001), DN (P < 0.0001), vasculitis (P < 0.0001) and amyloidosis (P < 0.0001) occurred more frequently and IgAN (P < 0.0001), lupus nephritis (P < 0.0001) and minimal change disease (P < 0.0001) occurred less frequently in the elderly. CONCLUSION This study is the first and largest renal biopsy series to analyze patients aged ≥65 years in China, and the results obtained from this study may increase the knowledge of renal diseases in elderly patients.

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.

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.

Evaluation of Glomerular Filtration Rate Using Cystatin C in Diabetic Patients Analysed by Multiple Factors Including Tubular Function

This study was designed to evaluate the usefulness of serum cystatin C (CysC) as a marker of renal function in 83 patients with diabetic nephropathy, considering multiple factors including tubular function and body mass index. Serum CysC was assayed using a particle-enhanced nephelometric immunoassay and the glomerular filtration rate (GFR) was obtained by measuring the plasma disappearance of the isotope 99mTc-diethylenetriamine penta-acetic acid. By comparing the correlation of CysC and serum creatinine (SCr) with GFR, it was concluded that CysC may be a better indicator of GFR than SCr in diabetic patients, in both the early hypertransfusion stage and in the late renal dysfunction stage. CysC showed a slightly higher sensitivity for renal function evaluation than SCr in patients with renal tubular dysfunction and moderate to severe proteinuria. In addition, CysC was not affected by the metabolic index. Thus, CysC may serve as an ideal endogenous marker of GFR in patients with diabetic nephropathy.

Clindamycin-induced acute kidney injury: large biopsy case series.

Background: While clindamycin-induced acute kidney injury (AKI) is uncommon, it has occurred more frequently in recent years. Summary: We investigated 24 patients diagnosed with clindamycin-induced AKI retrospectively. The dosage of clindamycin was 1.0-1.5 g/day. Fifteen patients had episodes of gross hematuria, but fever, skin rash and eosinophilia were rare. Urine analysis revealed mild proteinuria and severe tubular dysfunction. Twenty-three patients were diagnosed with AKI stage 3 upon admission. The clindamycin lymphocyte transformation assay was positive for 63.2% of the patients. Acute interstitial nephritis (AIN) and acute tubular necrosis (ATN) were proven by renal biopsy, and renal insufficiency appeared to result from tubular toxicity and drug crystals. In the majority (87.5%) of the patients, AKI was severe and required renal replacement therapy, but all of their renal function recovered significantly 2 months after discharge. Clindamycin-induced AKI is largely reversible and has episodes of gross hematuria. Renal biopsies confirmed AIN or ATN in these patients.

Identification of G8969>A in mitochondrial ATP6 gene that severely compromises ATP synthase function in a patient with IgA nephropathy

Here we elucidated the pathogenesis of a 14-year-old Chinese female who initially developed an isolated nephropathy followed by a complex clinical presentation with brain and muscle problems, which indicated that the disease process was possibly due to a mitochondrial dysfunction. Careful evaluation of renal biopsy samples revealed a decreased staining of cells induced by COX and NADH dehydrogenase activities, and a strong fragmentation of the mitochondrial network. These anomalies were due to the presence of a mutation in the mitochondrial ATP6 gene, G8969>A. This mutation leads to replacement of a highly conserved serine residue at position 148 of the a-subunit of ATP synthase. Increasing the mutation load in cybrid cell lines was paralleled by the appearance of abnormal mitochondrial morphologies, diminished respiration and enhanced production of reactive oxygen species. An equivalent of the G8969>A mutation in yeast had dramatic consequences on ATP synthase, with a block in proton translocation. The mutation was particularly abundant (89%) in the kidney compared to blood and urine, which is likely the reason why this organ was affected first. Based on these findings, we suggest that nephrologists should pay more attention to the possibility of a mitochondrial dysfunction when evaluating patients suffering from kidney problems.

The role of renal damage on cardiac remodeling in patients with diabetic nephropathy.

BACKGROUND Cardiovascular damage and diabetic nephropathy are major complications in patients with Type 2 diabetic nephropathy (T2DN); however, the role of renal damage on cardiac remodeling is not yet fully known. METHODS A retrospective research was conducted in 254 T2DN patients. All were divided into three groups according to urinary albumin excretion (UAE): the normoalbuminuria group (UAE < 30 mg/g, n = 18), the microalbuminuria group (UAE 30 - 300 mg/g, n = 99) and the macroalbuminuria group (UAE > 300 mg/g, n = 137). The parameters of cardiac remodeling, left atrial diameter (LAD), left ventricular diameter at the end of diastole (LVDd), interventricular septum (IVS), posterior wall of left ventricle (PWLV) and ejection fraction (EF), were determined by Doppler echocardiography. The effects of renal damage on cardiac remodeling were analyzed. RESULTS Among the 254 patients, LAD and LVDd enlargement was found in 180 (70.86%) and 53 (20.86%) patients, respectively; 46 cases (18.11%) suffered from both LAD and LVDd enlargement. Compared with normal LAD/LVDd groups, creatinine clearance (Ccr) and hemoglobin (Hb) were significantly lower in the left atrial (LA) and left ventricular (LV) dilated groups. LAD was positively correlated with mesangial sclerosis, tubular-interstitial lesions, interstitial fibrosis, as well as tubular basement membrane thickness (r = 0.273, 0.208, 0.176, 0.155, p < 0.05, respectively). Moreover, in comparison to patients with LA enlargement, more severe renal damage was detected in patients with LV enlargement. CONCLUSION There is a strong correlation between echocardiographic parameters and kidney lesions in patients with T2DN in China; the more severe the renal damage, the more severe the cardiac structural alteration. Renal damage contributes to cardiac remodeling, which may provide new insights into the pathogenesis of cardiovascular complications ,in diabetes mellitus.

Comparing the GFR estimation equations using both creatinine and cystatin c to predict the long-term renal outcome in type 2 diabetic nephropathy patients

AIMS This study aimed to determine whether eGFRcre-cys and its slope could improve the prediction of the long-term renal outcome in patients with type 2 diabetic nephropathy (DN). METHODS The cross-sectional and longitudinal analyses included 501 type 2DN patients from 2003 to 2009. GFR was estimated using either eGFRcre-cys or the serum creatinine-based equation (eGFRcre) or the cystatin C-based equation (eGFRcys), and was classified into 3 categories (≥90, 60-90, ≤60ml/min per 1.73m2). The proportion of patients was evaluated in each creatinine-calculated eGFR category for which the category was reclassified based on either cystatin C or the combined measurement. Long-term changes in eGFRcre-cys, eGFRcys and eGFRcre were estimated using linear mixed effect models. The receiver operating characteristic (ROC) curves was applied to study the sensitivity and specificity of different eGFR slopes for predicting the renal endpoint. RESULTS In the cross-sectional analyses, eGFRcre was overestimated compared to eGFRcre-cys [median bias -8.5 (95% CI: -25.01, 1.21)]. The reclassification of eGFRcre to a higher value was associated with an increased risk of ESRD [OR: 4.01 (95% CI: 2.36 to 6.82)]. In the longitudinal analyses for predicting end-stage renal disease (ERSD), the ROC curves for eGFRcre-cys (AUC=0.86±0.03) over 24months were increased compared with the ROC curves for eGFRcre and eGFRcys (p<0.05). CONCLUSIONS The study suggests that the eGFRcre-cys equation may be more precise and sensitive for predicting the renal outcome in T2DN patients. Tracking renal decline using eGFRcre-cys may be used as a surrogate for determining the renal endpoint in a clinical setting.