High remnant cholesterol as a risk factor for developing chronic kidney disease in patients with prediabetes and type 2 diabetes: a cross-sectional study of a US population.

AIMS: To examine any potential links between remnant cholesterol (RC) and comorbid chronic kidney disease (CKD) in individuals with prediabetes and type 2 diabetes mellitus (T2DM). METHODS: We used data from 2709 American people aged > 20 years from the National Health and Nutrition Examination Survey (NHANES) during 2011-2018. Subjects were categorized according to whether they had comorbid CKD. Logistic regression models and smoothed curve fitting methods were employed to assess the association of RC with comorbid CKD in patients with prediabetes and T2DM. RESULTS: The 2709 participants included 1473 patients with T2DM and 1236 with prediabetes [impaired glucose tolerance (IGT) and impaired fasting glucose (IFG)], of whom 744 (27.46%) had comorbid CKD. In multivariate-adjusted analysis, both RC and triglycerides (TG) were significantly associated with an increased risk of comorbid CKD, and a 1 mmol/L elevation of RC increased the risk by 38.1% [OR (95% CI) 1.636 (1.242, 2.156)], which was higher than the risk associated with a 1 mmol/L increase in TG [1.255 (1.106, 1.424)]. Additionally, those in the highest quartile of RC had a 43.6% higher risk of concomitant renal damage than those in the lowest quartile. RC was linearly and positively associated with the incidence of comorbid CKD in this population. CONCLUSIONS: RC is an independent risk factor for comorbid CKD in patients with prediabetes and T2DM. This finding provides a novel insight into the management and early detection of renal disease in patients with impaired glucose metabolism.

Clinicopathological features and long-term prognosis of glomerular diseases associated with mercury-containing cosmetics.

OBJECTIVE: The pathological types and long-term prognosis of glomerular diseases related to mercury exposure are unclear. This study retrospectively examined 41 cases of glomerulonephropathy caused by mercury-containing cosmetics. METHODOLOGY: Forty-one subjects with glomerular diseases presumably caused by mercury-containing cosmetics were selected. Clinical features, kidney biopsy, treatment, and follow-up data were collected. RESULTS: All patients were female with an average age of 39.4 ± 6.6 years at diagnosis. Median time of exposure to mercury-containing cosmetics was six months, and average urine mercury level was 66.80 ± 38.55ug/(g·Cr). Most patients presented with nephrotic syndrome. Renal histopathology showed membranous nephropathy in 22 patients (53.65%), minimal change disease in 13 patients (31.71%), IgA nephropathy with minimal change disease in 5 patients (12.20%), and focal segmental glomerulosclerosis in 1 patient. Median time of exposure to mercury was longer and the proportion of patients with autoantibodies (mainly antinuclear antibodies) was higher in patients with membranous nephropathy. Both blood phospholipase A2 receptor -Ab and kidney tissue phospholipase A2 receptor were negative. Thirty-six patients received glucocorticosteroids and/or immunosuppressants. Five patients were treated with an angiotensin receptor blocker, and nine patients were treated with chelation therapy. The median follow-up time was 40 months (range 27-94). All patients achieved complete remission, and the median time to complete remission was one month. They all successfully discontinued the drugs without relapsing; withdrawal time was 26 months. CONCLUSION: Membranous nephropathy was the most common pathological type in mercury-induced glomerular disease. Patients were sensitive to glucocorticosteroids and immunosuppressants and achieved complete remission quickly. Contrary to primary glomerulonephritides, patients with mercury-induced glomerular diseases had no relapses after withdrawal of the mercury containing cosmetics.

Nomogram analysis of the influencing factors of rapid renal decline in patients with biopsy-proven diabetic nephropathy in type 2 diabetes.

BACKGROUND: HbA1c variability may be related to risk of poor prognoses in chronic kidney disease patients with type 2 diabetes mellitus (T2DM). The aim of this study was to investigate whether HbA1c variability is associated with rapid renal function decline and the related risk factors in type 2 diabetic nephropathy (DN). MATERIALS AND METHODS: An observational analysis was performed on 387 DN patients who were diagnosed by kidney biopsy from January 2006 through January 2016 at the Department of Nephrology, Jinling Hospital Affiliated to Nanjing University. The rapid decliners were defined as an estimated glomerular filtration rate (eGFR) decline slope ≥ 5 mL/min/1.73m2/year. HbA1c variability and 24 baseline clinicopathologic parameters was evaluated using the least absolute shrinkage and selection operator regression (LASSO) and multivariate logistic regression. The nomogram method was applied to score the factors, and a scoring model was constructed. RESULTS: HbA1c variability positively correlated with the rate of renal function decline (r = 0.277; p < 0.001). Higher baseline eGFR, lower serum calcium concentration, glomerular lesions, arteriosclerosis, and interstitial fibrosis and tubular atrophy (IFTA) were selected into the nomogram. The calibration curve for the probability of survival showed good agreement between the prediction by nomogram and actual observation. The C-index for predicting survival was 0.811 (95% confidence interval (CI) 0.680 - 0.785). CONCLUSION: The proposed nomogram and score provide a useful risk estimate of fast renal function decline in patients with type 2 diabetic nephropathy.

Effect of high density lipoprotein cholesterol (HDL-C) on renal outcome in patients with nephrotic syndrome complicated with steroid-induced diabetes mellitus(SIDM).

OBJECTIVE: We aimed to investigate the renal prognosis of patients with idiopathic nephrotic syndrome (INS) complicated with steroid-induced diabetes mellitus (SIDM), the association of high-density lipoprotein cholesterol (HDL-C) before glucocorticoid treatment with renal prognosis, and the risk for persistent diabetes among patients with INS who had withdrawn from steroid therapy. MATERIALS AND METHODS: We retrospectively analyzed 239 patients with INS complicated with SIDM at the National Clinical Research Center of Kidney Diseases, Jinling Hospital, from January 2008 to December 2019. The primary endpoint was the composite renal outcome defined as the development of end-stage renal disease (ESRD) or a 50% decrease in estimated glomerular filtration rate (eGFR) for more than 24 months after glucocorticoid withdrawal. The secondary endpoint was persistent diabetes, defined as fulfilling the criteria for diagnosing diabetes or using antidiabetic medications for at least 24 months after glucocorticoid withdrawal. RESULTS: After glucocorticoid withdrawal for over 24 months, 35 (14.6%) patients reached the composite renal endpoint: end-stage renal disease (n = 14) or a 50% decrease in eGFR (n = 21). Before glucocorticoid therapy, a level of HDL-C greater than 1.45 mmol/L worsened renal survival in patients with INS complicated with SIDM. The log10 the level of HDL-C before glucocorticoid treatment was an independent risk factor for the renal outcome. A prediction model was generated: Hazard ratio (renal outcome) = 0.94 * hypertension before glucocorticoid therapy + 2.29 * log10 level of HDL-C before glucocorticoid treatment + 0.90 * the grade of interstitial tubule injury (AUROC, 0.75; 95% CI, 0.63 to 0.87; P < 0.01). Meanwhile, a level of fasting plasma glucose (FPG) before glucocorticoid treatment greater than 5.2 mmol/L enhanced the likelihood of persistent diabetes for at least 24 months after glucocorticoid withdrawal. CONCLUSIONS: Increased level of HDL-C before glucocorticoid therapy was independently associated with a higher risk for renal outcome and thus may be useful in the renal prognosis of patients with INS complicated with SIDM.

Efficacy of long-term repeated rituximab treatment in refractory phospholipase A2 receptor-antibody-related membranous nephropathy.

Aims: To evaluate the efficacy of long-term repeated rituximab treatment in refractory PLA2R-Ab-related membranous nephropathy (MN). Materials & methods: Rituximab was administered at a single dose of 375 mg/m2 and repeated if peripheral B-cell levels were >5/ul in 46 patients with refractory PLA2R-Ab-related MN. Results: The median frequency of rituximab treatment was 3 (IQR 2.0-4.0). A total of 32 (32/46) patients achieved remission (completed remission [CR] or partial remission [PR]) over a median time of 17.0 months, and 10 patients eventually progressed to CR. The proportion of serum PLA2R-Ab depletion was 73.91% (34/46) over a median time of 9 months. Antibody depletion preceded proteinuria remission. Conclusions: Long-term repeated rituximab treatment achieved high kidney and immunological response rates in refractory PLA2R-Ab related MN, and antibody depletion was a prerequisite for proteinuria remission.

Membranous nephropathy (MN) is the leading cause of proteinuria in adults and is mainly manifested as edema. Phospholipase 2 receptor (PLA2R) antibody is detected in 70­80% of patients with MN. Its main treatments are immunosuppressive therapies. The efficacy of traditional immunosuppressant drugs including steroids and alkylating and calcineurin inhibitors in reducing proteinuria have been confirmed; however, several adverse events such as diabetes mellitus, infections, cancer and kidney injury have been reported. Rituximab, a monoclonal antibody against CD20 on B cells, has been verified to be effective, safer and better tolerated in MN. However, the optimal rituximab regimen for MN has not yet been established. Here, we use B-cell-driven long-term repeated rituximab regimen and determine its exciting efficacy for refractory MN.

Case Report: Identification of a Novel Variant (m.8909T>C) of Human Mitochondrial ATP6 Gene and Its Functional Consequences on Yeast ATP Synthase.

With the advent of next generation sequencing, the list of mitochondrial DNA (mtDNA) mutations identified in patients rapidly and continuously expands. They are frequently found in a limited number of cases, sometimes a single individual (as with the case herein reported) and in heterogeneous genetic backgrounds (heteroplasmy), which makes it difficult to conclude about their pathogenicity and functional consequences. As an organism amenable to mitochondrial DNA manipulation, able to survive by fermentation to loss-of-function mtDNA mutations, and where heteroplasmy is unstable, Saccharomyces cerevisiae is an excellent model for investigating novel human mtDNA variants, in isolation and in a controlled genetic context. We herein report the identification of a novel variant in mitochondrial ATP6 gene, m.8909T>C. It was found in combination with the well-known pathogenic m.3243A>G mutation in mt-tRNALeu. We show that an equivalent of the m.8909T>C mutation compromises yeast adenosine tri-phosphate (ATP) synthase assembly/stability and reduces the rate of mitochondrial ATP synthesis by 20-30% compared to wild type yeast. Other previously reported ATP6 mutations with a well-established pathogenicity (like m.8993T>C and m.9176T>C) were shown to have similar effects on yeast ATP synthase. It can be inferred that alone the m.8909T>C variant has the potential to compromise human health.

Influence of guideline adherence and parameter control on the clinical outcomes in patients with diabetic nephropathy.

INTRODUCTION: We assessed the association between guideline adherence and outcomes of clinical parameter control and end-stage kidney disease (ESKD), and further studied the effect of parameter control on ESKD for Chinese patients with diabetic nephropathy (DN). RESEARCH DESIGN AND METHODS: In this retrospective study, 1128 patients with DN (15,374 patient-visit samples) diagnosed by renal biopsy were enrolled. Samples were classified as adherence and nonadherence based on whether prescribed drugs conformed to medication regimen and drug contraindication recommended by guidelines, including American Diabetes Association (ADA) and Chinese guidelines. Guideline adherence rate was calculated on all samples for antihyperglycemic, antihypertensive and lipid-lowering treatments. Clinical parameter control was compared after 3-6 months' therapy between two groups by generalized estimating equation models. Time-dependent Cox models were applied to evaluate the influence of guideline adherence on ESKD. Latent class mixed model was used to identify distinct trajectories for parameters and their ESKD risks were compared using Cox proportional-hazards models. RESULTS: Guideline adherence rate of antihyperglycemic therapy was the highest, with 72.87% and 68.15% of samples meeting ADA and Chinese guidelines, respectively. Adherence was more likely to have good glycated hemoglobin A1c (HbA1c) control (ADA: OR 1.46, 95% CI 1.12 to 1.88; Chinese guideline: OR 1.42, 95% CI 1.09 to 1.85) and good blood pressure control (ADA: OR 1.35, 95% CI 1.03 to 1.78; Chinese guideline: OR 1.39, 95% CI 1.08 to 1.79) compared with nonadherence. The improvement of patient's adherence showed the potential to reduce ESKD risk. For proteinuria, low-density lipoprotein cholesterol (LDL-C), systolic blood pressure and uric acid, patients in higher-value trajectory group had higher ESKD risk. Proteinuria and LDL-C trajectories were most closely related to ESKD risk, while the risk was not significantly different in HbA1c trajectories. CONCLUSIONS: Guideline adherence and good control of proteinuria and LDL-C in clinical practice are important and in need for improving clinical outcomes in patients with DN.

Role of complement system in patients with biopsy-proven immunoglobulin G4-related kidney disease.

Hypocomplementemia has been frequently reported in immunoglobulin G4-related kidney disease (IgG4-RKD). However, studies on the role of complement system in IgG4-RKD are lacking. A total of 40 429 renal biopsies from January 2010 to January 2018 were reexamined in the present study, and 17 patients were confirmed to meet the criteria of IgG4-RKD. According to the serum C3 levels, they were divided into 2 groups: the low-C3 group (C3 <0.8 g/L, n = 7) and the normal-C3 group (C3 ≥0.8 g/L, n = 10). Compared with the normal-C3-level group, the patients in the low-C3-level group had lower serum C4 concentrations (P = .025), higher serum IgG4 concentrations (P = .003), higher positive rates in rheumatoid factor (P = .033), more severe storiform fibrosis (P = .007) at diagnosis, and higher blood urea nitrogen levels at the latest test (P = .04). The serum levels of C3 were in negative correlation with the serum levels of IgG4 (P = .003), the levels of rheumatoid factor (P = .002), renal deposition of C1q (P = .028), storiform fibrosis (P < .001), scores of interstitial fibrosis (P = .015), the amount of renal IgG4-positive (IgG4+) plasma cells (P = .020), the ratios of IgG4+ plasma cells/CD138+ cells (P = .018), and the blood urea nitrogen concentrations at the last test (P = .023). Our study shows that IgG4-RKD is a relatively rare entity. Complement system may participate in the development of IgG4-RKD.

Risk factors for infectious complications of ANCA-associated vasculitis: a cohort study.

BACKGROUND: Severe infections are common complications of immunosuppressive treatment for antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) with renal involvement. We investigated the clinical characteristics and risk factors of severe infection in Chinese patients with AAV after immunosuppressive therapy. METHODS: A total of 248 patients with a new diagnosis of ANCA-associated vasculitis were included in this study. The incidence, time, site, and risk factors of severe infection by the induction therapies were analysed. Multivariate Cox proportional hazards models were used to calculate hazard ratios (HRs) with 95% confidence intervals (CI). RESULTS: A total of 103 episodes of severe infection were identified in 86 (34.7%, 86/248) patients during a median follow-up of 15 months. The incidence of infection during induction therapy was 38.5% for corticosteroids (CS), 39.0% for CS+ intravenous cyclophosphamide (IV-CYC), 33.8% for CS+ mycophenolate mofetil and 22.5% for CS + tripterygium glycosides, 76 (73.8%) infection episodes occurred within 6 months, while 66 (64.1%) occurred within 3 months. Pneumonia (71.8%, 74/103) was the most frequent type of infection, and the main pathogenic spectrum included bacteria (78.6%), fungi (12.6%), and viruses (8.7%). The risk factors associated with infection were age at the time of diagnosis (HR = 1.003, 95% CI = 1.000-1.006), smoking (HR = 2.338, 95% CI = 1.236-4.424), baseline secrum creatinine (SCr) ≥5.74 mg/dl (HR = 2.153, 95% CI = 1.323-3.502), CD4+ T cell< 281 µl (HR = 1.813, 95% CI = 1.133-2.900), and intravenous cyclophosphamide regimen (HR = 1.951, 95% CI =1.520-2.740). Twelve (13.9%) patients died of severe pneumonia. CONCLUSION: The infection rate during induction therapy was high in patients with AAV. Bacterial pneumonia was the main type of infection encountered. Age at the time of diagnosis, smoking, baseline SCr ≥5.74 mg/dl, CD4+ T cell< 281 µl, and IV-CYC therapy were identified as risk factors for infection.

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.

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.

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.

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.

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.

Treatment of diabetic nephropathy with Tripterygium wilfordii Hook F extract: a prospective, randomized, controlled clinical trial.

BACKGROUND: Diabetic nephropathy (DN) is the most common cause of end-stage renal failure. Although angiotensin II receptor blockers (ARBs) can be used to attenuate proteinuria in DN patients, their efficacy remains limited. This clinical trial aimed to evaluate the efficacy of Tripterygium wilfordii Hook F (TwHF) extract in the treatment of type 2 diabetes mellitus (DM)-induced nephropathy. METHODS: A total of 65 DN patients with proteinuria levels ≥ 2.5 g/24 h and serum creatinine levels<3 mg/dl were enrolled in this six-month, prospective, randomized, controlled study. The patients were randomized into treatment groups that received either 120 mg of TwHF extract per day for three months, followed by 60 mg per day for three more months, or 160 mg of valsartan daily for six months. The urinary protein and estimated glomerular filtration (eGFR) level were measured at one, three, and six months after the commencement of treatment. The primary measure of treatment efficacy was a reduction in the 24-h urine protein level between baseline and the end of the study, and the secondary measure of treatment efficacy was a reduction in the eGFR value. RESULTS: At the end of the treatment period, the mean urine protein level in the TwHF group was dramatically decreased (4.99 ± 2.25 g/24 h vs 2.99 ± 1.81 g/24 h, p< 0.01), with decreases at one, three, and six months of 32.9%, 38.8%, and 34.3%, respectively. In contrast, the proteinuria in the valsartan group was not significantly attenuated, and the decreases in urine protein levels at treatment months one, three, and six were 1.05%, 10.1%, and -11.7%, respectively. The mean decrease in eGFR in the valsartan group was greater than that in the TwHF group (26.4% vs. 13.7%, respectively; p =0.067). CONCLUSIONS: TwHF extract can reduce the urine protein level of DN patients and represents a novel, potentially effective, and safe drug for the treatment of DN patients with proteinuria. TRIAL REGISTRATION: ClinicalTrials.gov: NCT00518362.

The relationship between obesity and diabetic nephropathy in China.

BACKGROUND: The epidemic of diabetic nephropathy (DN) has been paralleled by rapid increases in both obesity and diabetes in China. The aim of this study was to investigate the natural history of DN and the association of obesity and renal function with diabetes. METHODS: In total, 264 patients with renal biopsy-confirmed DN were examined from 2002 to 2008 and followed up to June 2008 in our institute. Among these, 129 patients were classified into a Kidney Disease Outcomes Quality Initiative (K/DOQI) stage I subgroup. Weight status, clinico-histopathological features, the development of end-stage renal disease (ESRD) and increased proteinuria were evaluated at the baseline of biopsy and during the follow up. Lean, overweight and obese phenotypes were defined as body mass index (BMI) less than 25 kg/m2, 25-28 kg/m2, and more than 28 kg/m2 over, respectively. RESULTS: In the patients with renal biopsy-confirmed DN, BMI was 25.5 ± 3.39 kg/m2, with 122 (46.2%), 83 (31.4%) and 59 (22.3%) having lean, overweight and obese phenotypes, respectively. Mean proteinuria was 3.09 ± 2.32 g/24 h, serum creatinine was 2.02 ± 2.02 mg/dL, and creatinine clearance rate (Ccr) was 96.0 ± 54.0 mL/min/1.73 m2. Compared with obese patients, lean patients had a lower Ccr, a higher percentage of anemia, more renal lesions and higher risk for ESRD (HR = 1.812, P = 0.048). The weight in obese patients decreased significantly after 27 months, and lean patients had a longer duration of diabetes than obese patients. Regarding patients at K/DOQI stage I, patients with DN showed similar duration of diabetes regardless of weight status. Minimal weight loss was recorded in obese patients during follow-up, and they exhibited greater glomerular hyperfiltration and higher risk for increased proteinuria (HR = 2.872, P = 0.014) than lean patients. CONCLUSIONS: In China, obesity is common in DN patients undergoing biopsy. Initial high levels of proteinuria and subsequent weight loss are the major characteristics of the natural course of DN. Obesity contributed to increased proteinuria at an early stage, while the lean phenotype was associated with ESRD development, especially at the later stages.

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.

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.

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.