少量蛋白尿和（或）血尿IgA肾病临床病理分析

目的 了解表现为少量蛋白尿和（或）血尿IgA肾病（IgAN）患者的肾脏病理特征及其与临床表现的关系。 方法 对1993年1月至2009年10月肾活检确诊为IgAN,且表现为少量蛋白尿 （<1 g/24 h）和（或）血尿,Scr<133 μmol/L的患者的临床和病理资料进行回顾性分析。病理学分级参照Lee分级及Katafuchi半定量积分标准。应用多因素logistic回归法分析肾脏病理损伤的危险因素。 结果 符合入选标准共316例,男123例,女193例,肾穿时年龄（33.10±10.69）岁。蛋白尿伴血尿占84.5%、单纯血尿占7.6%、单纯蛋白尿占7.9%。16.5%患者伴有高血压。CKD1、2、3期分别占76.9%、20.9%和2.2%。Lee Ⅲ级及以上患者占31.3%。52.8%患者有不同程度肾小球硬化;20.3%伴新月体形成;22.5%伴小管萎缩;16.8%有间质纤维化;24.7%有血管病变。肾小球硬化积分与估算肾小球滤过率（eGFR）呈负相关;与蛋白尿及平均动脉压（MAP）呈正相关。肾小管间质病变积分与eGFR及血红蛋白(Hb)呈负相关;与尿蛋白量呈正相关。血管病变积分与MAP呈正相关;与eGFR呈负相关(均P < 0.05)。多因素logistic回归分析结果显示,肾活检时尿蛋白量（OR = 8.564,P < 0.01）、Scr（OR = 1.031,P< 0.01）及Hb（OR = 0.975,P < 0.01）是肾脏病理损伤（LeeⅢ级以上）的独立危险因素。 结论 部分表现为少量蛋白尿和（或）血尿IgAN患者的病理改变并不轻,且肾功能已减退。尿蛋白量、Scr、Hb是预测肾脏病理损伤程度的独立危险因素。肾活检对这些患者明确诊断、判断病情和预后、制定个体化治疗方案十分重要。     

Risk of Adverse Pregnancy Outcomes in Women with CKD

CKD is increasingly prevalent in pregnancy. In the Torino-Cagliari Observational Study (TOCOS), we assessed whether the risk for adverse pregnancy outcomes is associated with CKD by comparing pregnancy outcomes of 504 pregnancies in women with CKD to outcomes of 836 low-risk pregnancies in women without CKD. The presence of hypertension, proteinuria (>1 g/d), systemic disease, and CKD stage (at referral) were assessed at baseline. The following outcomes were studied: cesarean section, preterm delivery, and early preterm delivery; small for gestational age (SGA); need for neonatal intensive care unit (NICU); new onset of hypertension; new onset/doubling of proteinuria; CKD stage shift; “general” combined outcome (preterm delivery, NICU, SGA); and “severe” combined outcome (early preterm delivery, NICU, SGA). The risk for adverse outcomes increased across stages (for stage 1 versus stages 4–5: “general” combined outcome, 34.1% versus 90.0%; “severe” combined outcome, 21.4% versus 80.0%; P<0.001). In women with stage 1 CKD, preterm delivery was associated with baseline hypertension (odds ratio [OR], 3.42; 95% confidence interval [95% CI], 1.87 to 6.21), systemic disease (OR, 3.13; 95% CI, 1.51 to 6.50), and proteinuria (OR, 3.69; 95% CI, 1.63 to 8.36). However, stage 1 CKD remained associated with adverse pregnancy outcomes (general combined outcome) in women without baseline hypertension, proteinuria, or systemic disease (OR, 1.88; 95% CI, 1.27 to 2.79). The risk of intrauterine death did not differ between patients and controls. Findings from this prospective study suggest a “baseline risk” for adverse pregnancy-related outcomes linked to CKD.     

Relationship between interventricular septum thickness and renal function in patients with type 2 diabetes mellitus

Objective To investigate the relationship between interventricular septum thickness(IVS) and renal function in patients with diabetes mellitus. Methods Two hundred and sixty-five patients of type 2 diabetes without dialysis were enrolled in a cross-sectional study. According to their IVS, the patients were divided into normal group (IVS≤11 mm) and higher IVS group (IVS＞11 mm). All patients according to evaluated glomerular filtration rate (eGFR) level were divided into eGFR≥60 ml?min-1?(1.73 m2)-1 group and eGFR＜60 ml?min-1?(1.73 m2)-1 group. The demographic characteristic, biochemical examination, eGFR, and proteinuria of different groups were compared. Pearson or spearman correlation was used to analyze the relationship between eGFR, IVS and other parameters. eGFR＜60 ml?min-1?(1.73 m2)-1 and IVS thickening were analyzed by binary logistic regression. Risk factors affect the prognosis of renal function in patients with diabetes mellitus were analyzed by Cox regression analysis. Results Compared with normal group, patients in the higher IVS group had higher systolic pressure (P=0.002), their level of Scr, BUN, 24 h urinary protein were increased (all P＜0.05), while the level of eGFR, albumin (ALB), hemoglobin (Hb) and fasting blood glucose were decreased (all P＜0.05). The prevalence of hypertension was increased (81.16% vs 58.67%, χ2=11.273, P=0.001), and there was also a difference in the proportion of patients in each stage of CKD (χ2=34.593, P＜0.001). Correlation analysis showed that IVS was positively correlated with BMI, systolic BP, Scr, BUN, 24 h urinary albumin, 24 h urinary protein (all P＜0.05), while negative correlation was observed between the thickened degree of IVS and Hb, albumin, eGFR and total calcium (all P＜0.05). It's worth noting that IVS also correlated with history of hypertension and degree of renal injury (all P＜0.01). Logistic regression analysis showed that longer duration of diabetes, higher systolic pressure and BUN were independent risk factors for eGFR＜60 ml?min-1?(1.73 m2)-1 (all P＜0.05), while higher Hb and Alb were independent protective factors for eGFR＜60 ml?min-1?(1.73 m2)-1 (all P＜0.05). Logistic regression analysis also showed that the baseline increased Scr was independent risk factor for interventricular thickening (P＜0.05), while the increase of fasting blood-glucose was independent protective factor for interventricular thickening (P＜0.05). Cox regression analysis showed that interventricular thickening was an independent risk factor in predicting the progression of type 2 diabetes (HR=1.396, 95%CI=1.098-1.774, P=0.006). Conclusion Interventricular septum thickness is closely related to the state of renal function, as well as is an independent risk factor to predict kidney function decline in patients with type 2 diabetes.     

Analysis of incidence and risk factors of renal insufficiency in solitary kidney patients

Objective To investigate the incidence of renal insufficiency in solitary kidney patients and analyze the risk factors. Methods Patients with solitary kidney who were admitted to the Second Hospital of Lanzhou University from January 2012 to January 2019 were retrospectively selected as subjects. According to estimated glomerular filtration rate (eGFR) level, the patients were divided into two groups: eGFR＜60 ml?min-1?(1.73 m2)-1 group and eGFR≥60 ml?min-1?(1.73 m2)-1 group. The data of the general information, laboratory examinations and kidney size were collected, and the differences of the above indicators between the two groups were compared. Logistic regression model was used to analyze the related factors of renal function decline. Results (1) A total of 323 solitary kidney patients with age of (53.8±15.8) years and median duration of 10.0 years were enrolled in the study, including 203 males (62.8%). There were 150 cases (46.4%) with hypertension, 136 cases (42.1%) with proteinuria, and 134 cases (41.5%) with renal insufficiency, even 29 cases(9.0%) had developed into end-stage renal disease. (2) Compared with those in eGFR≥60 ml?min-1?(1.73 m2)-1group, patients in eGFR＜60 ml?min-1?(1.73 m2)-1 group had higher age, mean arterial pressure, serum creatinine, serum uric acid, fasting blood glucose, and higher proportion of hypertension and proteinuria, but had lower proportion of congenital solitary kidney, hemoglobin, plasma albumin and residual kidney diameter. The differences of above indicators were statistically significant ( all P＜0.05). (3) Logistic regression analysis showed that increasing age (every ten years, OR=1.752, 95%CI 1.455-2.109, P＜0.001), anemia (OR=2.327, 95%CI 1.356-3.994, P=0.002), hyperuricemia (OR=5.097, 95%CI 2.873-9.042, P＜0.001) and high urine protein level (every 1+, OR=1.515, 95%CI 1.197-1.919, P=0.001) were independent risk factors for renal dysfunction in solitary kidney patients. Conclusions The incidence of renal insufficiency in solitary kidney patients is 41.5%. Patients with solitary kidney may perform varying degrees of kidney damage, such as hypertension, proteinuria and eGFR decline. Increasing age, anemia, hyperuricemia and high urine protein level are independent risk factors for renal insufficiency in solitary kidney patients.     

Clinico-pathological characterization and outcome of primary focal segmental glomerular sclerosis with deposition of IgM

Objective To explore the clinico-pathological features and outcomes of primary focal segmental glomerular sclerosis with IgM deposition. Methods One hundred and two patients with primary focal segmental glomerular sclerosis (pFSGS) in Hangzhou hospital of traditional Chinese medicine between 1996 and 2012 were retrospectively studied. The patients were divided into IgM deposition group (n=66) with IgM deposition in glomeruli and none-IgM deposition group (n=36)without IgM deposition. Baseline and clinical characteristics of all FSGS patients were assessed and outcomes were reviewed. The survival rates of the patients were analyzed using theKaplan-Meiermethod. Results (1) There were not difference in age, sex ratio, incidence of microscopic hematuria, hypertension, renal insufficiency, eGFR, Ccr and Scr between two groups. However, proteinuria, incidence of nephrotic syndrome, urine microalbumin, urine NAG, serum cholesterol, serum high-density lipoprotein, and serum IgM in IgM deposition group were significantly higher than those in none-IgM deposition group (P＜0.05), serum albumin and serum IgA in IgM deposition group were significantly lower than those in none-IgM deposition group (P＜0.05). (2) The IgM deposition group had a significantly higher incidence of glomerular deposition of IgA, IgG, C3, C1q and fibrinogen than none-IgM deposition group (P＜0.05). The score of mesangial matrix proliferation in the IgM deposition group was lower than that in none-IgM deposition group (P＜0.05). (3) fifty-four patients (35 patients in IgM deposition group and 19 patients in none-IgM deposition group） were followed-up for a median of 64.6 (22.8, 103.8) months. Progression to renal failure was observed in 5 patients of IgM deposition group and none in none-IgM deposition group. Compared with the none-IgM deposition, the survival rates in the IgM deposition group were statistically lower (P＜0.05).Conclusions PFSGS patients with IgM deposition were severer in proteinuria, higher incidence ofIgA, IgG, C3, C1q and fibrinogen deposition in glomeruli and worse outcome than those without IgM deposition.     

Clinical and pathological features of hyperuricemia in children with IgA nephropathy at a single center

Objective To investigate the clinical, pathological features and risk factors of hyperuricemia in children with IgA nephropathy (IgAN). Methods A retrospective study of 269 primary IgAN children diagnosed between January 1, 2006 to December 31, 2017 at the Children Kidney Disease Center, the First Affiliated Hospital of Sun Yat-sen University, was performed in the hyperuricemia group (uric acid＞350 μmol/L) and the normal uric acid group. The clinical and pathological characteristics were analyzed, and the risk factors of hyperuricemia were analyzed by using multivariate logistic regression analysis. Results There were 185 males and 84 females in the 269 IgAN children with age of (9.2±3.1) years old, among whom there were 70 patients (26.0%) accompanied by hyperuricemia. Clinical indicators such as hypertension, urea nitrogen, serum creatinine, blood lipids, urinary protein in hyperuricemia group were higher than those in normal uric acid group (all P＜0.05), while estimated glomerular filtration rate, serum total protein and albumin were less (all P＜0.05). There were 58 patients (23.0%) and 12 patients (70.5%) associated with hyperuricemia among IgAN children with CKD 1-2 and CKD 3-5. The proportion of hyperuricemia in CKD stage 3-5 IgAN children was statistically higher than that in normal uric acid group (P＜0.01). The hyperuricemia group had a higher proportion of Lee IV and V grade, and a lower proportion of the Lee III grade than the normal uric acid group (all P＜0.05). According to the Oxford pathological classification score, there was no significant difference in total scores of renal lesions, glomerular score, and tubulointerstitial score between the two groups (all P＞0.05). According to the Katafuchi semi-quantitative score, there was no significant difference in the total scores of renal lesions, glomeruli, and tubulointerstitial scores (all P＞0.05), while the hyperuricemia group had higher renal vascular scores than the normal uric acid group (P＜0.01). Multivariate logistic regression analysis showed that hypertension (OR=12.596, 95%CI 1.778-89.243, P=0.011), higher total cholesterol (OR=1.192, 95%CI 1.064-1.336, P=0.002), higher urea nitrogen (OR=1.273, 95%CI 1.104-1.468, P=0.001), proteinuria 3+(OR=1.875, 95%CI 1.309-2.684, P=0.001), proteinuria 4+(OR=1.627, 95%CI 1.241-2.134, P＜0.001) and CKD stage 3 (OR=3.355, 95%CI 1.376-8.181, P=0.008) were the risk factors of hyperuricemia in children with IgAN. Conclusions Twenty-six percent IgAN children patients are accompanied by hyperuricemia, and their clinical parameters and pathological changes are more severe than those in normal uric acid group. Hypertension, higher total cholesterol, higher urea nitrogen, proteinuria 3+/4+ and CKD stage 3 are the risk factors of hyperuricemia in children with IgAN.     

Effect of urate-lowering therapy on renal function in chronic kidney disease stages 2-5

Objective To investigate the effect of urate-lowering therapy on renal function in chronic kidney disease (CKD) stages 2-5 patients with hyperuricemia (HUA). Methods A total of 132 patients of CKD stages 2-5 with HUA between July 2016 and December 2017 in Department of Nephrology of the Second Affiliated Hospital of Anhui Medical University were prospectively and self-controlled analyzed. Serum uric acid (SUA), estimated glomerular filtration rate (eGFR) and other clinical parameters were measured at baseline and after 1-6 months treatment. The patients were divided into group A (CKD stages 2-3a) and group B (CKD stages 3b-5) on the baseline value of eGFR. The changes of SUA and eGFR before and after treatment were compared. According to the level of SUA after 6 months treatment, patients were divided into attainment group (SUA＜360 μmol/L) and nonattainment group (SUA≥360 μmol/L). The difference of renal function in pre-treatment and post-treatment was compared. Multiple stepwise linear regression was used to analyze the relationship among the change of eGFR after receiving 6 months' treatment (deGFR) and SUA level, baseline eGFR and other indexes. Results After 1, 3, 6 months treatment, the average levels of SUA, Scr and urea nitrogen of all patients were decreased significantly while eGFR value was increased significantly (all P＜0.050) than those in pre-treatment period. After six-month-therapy, proteinuria and hematuria were improved significantly in all patients (P＜0.001, P=0.001). Compared with pre-treatment period, both the SUA levels of group A and group B were declined significantly while eGFR had a significant rise after treatment (P＜0.001). The change of eGFR post-treatment in group A was significantly higher than that of group B [(13.64±15.35) vs (8.97±9.79) ml?min-1?(1.73 m2)-1, P=0.044]. At 6 months after treatment, the eGFR value increased markedly in both attainment group and nonattainment group compared with pre-treatment period (P＜0.001). After six-month-therapy, the eGFR value in attainment group was increased more obviously than that of nonattainment group [(13.96±14.64) vs (8.03±9.69) ml?min-1?(1.73 m2)-1, P=0.021]. Multiple stepwise linear regression analysis showed that the baseline eGFR value was an influencing factor of deGFR (b=0.161, P=0.020). Conclusions The renal function of CKD stages 2-5 patients with HUA can be significantly improved by urate-lowering therapy, which can effectively reduce proteinuria and hematuria.     

系统性红斑狼疮并发继发性抗磷脂综合征肾损害11例临床病理分析

目的 分析系统性红斑狼疮（SLE）并发继发性抗磷脂综合征（APS）肾损害的临床病理表现,旨在提高对该类疾病的认识。 方法 回顾性分析北京协和医院2000年至2010年期间确诊SLE并发继发性APS（SLE伴APS）并行肾组织学检查的11例患者的资料,分析其临床病理特点,并比较其和SLE不伴APS患者在肾损害的临床病理及预后上的差异。 结果 11例SLE伴APS患者均有肾脏受累,突出表现为高血压（54.5%）、大量蛋白尿（≥3.5 g/d）（72.7%）和肾功能异常（45.5%）。SLE伴APS患者的舒张压、平均动脉压以及肾小球滤过率（eGFR）均明显高于SLE不伴APS患者（均P < 0.05）。8例（72.7%）SLE伴APS患者存在肾内血管的“血管闭塞性表现”,即符合抗磷脂综合征肾病（APSN）的病理表现,包括肾小血管、肾小球毛细血管血栓形成以及肾小动脉内膜增生、局灶性肾皮质萎缩、肾小管甲状腺样化,其中慢性APSN表现5例（45.5%）,急性APSN表现4例（36.4%）（其中1例同时有急性和慢性表现）;其APSN的发生率以及急性APSN的发生率明显高于SLE不伴APS患者（P < 0.05）。 结论 SLE并发APS肾损害患者除狼疮肾炎外,多并发APSN,临床上高血压和肾功能异常更为突出。     

Comparative analysis of clinico-pathological characteristics and outcomes in malignant hypertension patients with and without primary glomerular diseases

Objective To investigate the clinico-pathological characteristics, outcomes and their predictors in malignant hypertension related kidney injury with and without primary glomerular diseases. Methods Patients with clinical diagnosis of malignant hypertension, biopsy-proven kidney injury caused by malignant hypertension and complete clinical data from January 2010 to December 2018 were retrospectively analyzed. According to clinical and renal pathology, patients were divided into malignant hypertension related kidney injury without primary nephropathy group and with primary nephropathy group. Clinico-pathological characteristics and outcomes were evaluated and compared between malignant hypertension related kidney injury with and without primary glomerular diseases. Results Totally 31 biopsy-proven kidney injury patients were analyzed. Among them, there were 18 cases with primary glomerular diseases and 13 cases without primary glomerular diseases, with age of (32.5±6.5) years old and (34.7±8.1) years old, respectively. There were 12 males in both group. The proportion of primary IgA nephropathy was higher (16/18) in the group of malignant hypertension related kidney injury with primary glomerular diseases. Malignant hypertension with primary glomerular diseases patients had lower plasma albunin level [(32.7±6.4) g/L vs (38.5±7.3) g/L, P=0.027], higher 24-hour proteinuria level [(4.03±2.71) g vs (1.45±0.98) g, P=0.002] and higher incidence rates of dysmorphic hematuria (14/18 vs 0, P=0.001) than those without primary glomerular diseases patients. Glomerular sclerosis, mesangial proliferation, tubular atrophy and interstitial fibrosis were more severe in malignant hypertension with primary glomerular diseases patients (all P＜0.05), but the ischemic wrinkling of glomerular capillary was more severe in malignant hypertension without primary glomerular diseases (P＜0.01). There were no differences of acute or chronic malignant hypertensive injury in small artery and in afferent arterioles between the two groups. Cox regression analysis showed that loss of brush-border with flattening of tubular epithelium was the predictor for renal partial recovery (HR=5.956, 95%CI 1.198-29.614, P=0.029). Kaplan-Meier analysis showed that malignant hypertension patients with primary glomerular diseases had shorter renal survival time than those without primary glomerular diseases [(24.1±9.3) months vs (56.6±12.4) months], and accumulative renal survival rate of malignant hypertension patients with primary glomerular diseases was lower than that without primary glomerular diseases (11.6% vs 53.3%, Log-rank χ2=5.022, P=0.025). Multivariate Cox regression analysis showed that severe tubular atrophy and interstitial fibrosis were independent risk factors for end-stage renal disease in malignant hypertension patients (HR=5.870, 95%CI 1.372-25.112, P=0.017). Conclusions Malignant hypertension with primary glomerular diseases patients have more severe clinico-pathological renal impairment and poorer prognosis of long-term renal survival than those without primary glomerular diseases. Acute renal tubular injury (loss of brush-border with flattening of tubular epithelium) is the only predictor of renal function improvement in patients with malignant hypertension and renal impairment within one year. Tubular atrophy/interstitial fibrosis is a risk factor for end-stage renal disease in patients with malignant hypertension. Renal biopsy is an indispensable tool for predicting short-term and long-term renal outcomes.     

Antiproteinuric effect of oral paricalcitol in chronic kidney disease

BACKGROUND: Proteinuria is a marker of cardiovascular and renal disease in patients with chronic kidney disease (CKD), and reduction in proteinuria has been associated with improved cardiovascular and renal outcomes. While active vitamin D and its analogs have been shown to have renal protective effects in animals, these hormones have not been shown to reduce proteinuria in CKD patients. METHODS: In three double-blind, randomized, placebo-controlled studies to evaluate the safety and efficacy of oral paricalcitol, 220 CKD stage 3 and 4 patients with secondary hyperparathyroidism (SHPT) were randomized to oral paricalcitol (N= 107, mean dose 9.5 microg/week) or placebo (N= 113) and followed for up to 24 weeks. In conjunction with other safety measures, proteinuria was measured by dipstick and read by an automated reader at the beginning and end of trial. We subsequently analyzed the dipstick data to evaluate the effect of paricalcitol on proteinuria. RESULTS: At baseline, proteinuria was present in 57 patients randomized to oral paricalcitol and 61 patients randomized to placebo (NS). At the final visit, 29/57 (51%) of the paricalcitol patients compared to 15/61 (25%) placebo patients had reduction in proteinuria, P= 0.004 (odds for reduction in proteinuria 3.2 times greater for paricalcitol patients, 95% CI 1.5-6.9). For the patients who had both proteinuria at baseline and parathyroid hormone (PTH) suppression (end point defined as 2 consecutive > or =30% decreases in iPTH from baseline), 27/51 (53%) patients had a reduction in the proteinuria in the paricalcitol group and 0/7 (0%) had a reduction in proteinuria in the placebo group. Reduction of proteinuria favored patients on paricalcitol, regardless of age, sex, race, diabetes mellitus, hypertension, or use of therapies to block the renin-angiotensin-aldosterone system (RAAS). CONCLUSION: Our results demonstrate that the reduction in proteinuria was associated with paricalcitol treatment, and the reduction in proteinuria was independent of concomitant use of agents that block the RAAS. Paricalcitol as a potential pharmacologic means of reducing proteinuria in CKD patients warrants further investigation.     

慢性肾脏病患者成纤维细胞生长因子23与肾功能及钙磷代谢的关系

目的 探讨慢性肾脏病（CKD）患者随着肾功能的变化,其成纤维细胞生长因子23（FGF23）与钙磷代谢的关系。 方法 研究对象为2008年8月至2009年4月在上海交通大学附属第一人民医院肾内科住院的初诊CKD患者72例,按照肾小球滤过率（GFR）水平分为5组,另设健康对照组20例。抽取受试者静脉血并分离血清,以酶联免疫法检测FGF23、25（OH）VitD3、1,25（OH）2VitD3;全自动生化分析仪测量钙（Ca）、磷（P）、血肌酐（Scr）、尿素氮（BUN）、白蛋白（Alb）水平;免疫放射法测定全段甲状旁腺激素（iPTH）。 结果 CKD患者血清FGF23水平随GFR降低逐渐升高,在CKD4期和5期时,血FGF23、P、iPTH上升明显,1,25（OH）2VitD3显著下降,与CKD1期差异有统计学意义（均P < 0.05）。CKD2~3期与CKD1期的FGF23、P、Ca、iPTH、活性维生素D水平差异均无统计学意义。血Ca、25（OH）VitD3随着肾功能下降有降低趋势,但各期间差异均无统计学意义。Pearson相关分析显示,CKD1~5期logFGF23与P、logiPTH呈正相关（r = 0.653,P < 0.01;r = 0.800,P < 0.01）,与GFR、1,25（OH）2VitD3呈负相关（r = -0.753,P < 0.01;r = -0.265,P < 0.05),与Ca、25（OH）VitD3无相关。CKD1~3期logFGF23与logiPTH呈正相关(r = 0.374,P < 0.05),而与Ca、P、25（OH）VitD3、1,25（OH）2VitD3、GFR均无相关。CKD4~5期log FGF23与P、logiPTH呈正相关（r = 0.381,P < 0.05;r = 0.515,P < 0.01）,与GFR呈负相关（r = -0.654,P < 0.01）,与Ca、25（OH）VitD3、1,25（OH）2VitD3无相关。 结论 随着肾功能减退,血清FGF23、P、iPTH水平逐渐升高,活性维生素D水平逐渐下降,尤以CKD4~5期明显。在肾脏病早期阶段（CKD1~3期）血iPTH水平与FGF23有关。当GFR<30 ml/min时,肾功能状态、血磷、血iPTH均可影响血FGF23水平。     

妊娠并发肾病综合征的临床研究

目的 探讨妊娠并发肾病综合征患者的妊娠结局及肾功能的变化。 方法 回顾性调查我院2003年至2007年间59例妊娠并发肾病综合征患者的临床资料,包括患者出现肾病的时间、尿蛋白量、血浆白蛋白、Scr、血尿酸、血压;胎儿存活率、死亡率、早产率、出生体质量;以及孕妇产后随访蛋白尿、肾功能和血压情况。采用Logistic回归方法,分析影响妊娠患者的肾脏转归及胎儿预后的危险因素。 结果 孕妇出现蛋白尿孕周平均为（20.35±9.40）周,尿蛋白量（24 h）3.5~15.0 g,中位数5.1 g;血浆白蛋白10~28 g/L,中位数22.5 g/L;Scr 32~825 μmol/L,中位数84 μmol/L;血尿酸196~793 μmol/L,中位数385.5 μmol/L。妊娠高血压综合征发生率为75%,其中先兆子痫占55.5%。胎儿存活率72.9%（43/59）,其中早产占76.7%（33/43）;低体质量儿占62.8%（27/43）。产后50%患者持续肾病综合征。24例原有慢性肾炎,其中75%患者蛋白尿较怀孕前有不同程度的增加。38例伴有肾功能受损,其中36.8%患者产后肾功能受损加重,23.7%进入终末期肾衰竭;其中80%发生在Scr≥265 μmol/L的患者。89%患者产后持续高血压。Logistic 回归结果提示,孕期高尿酸血症（P=0.018,OR=1.012）和Scr升高（P=0.039,OR=1.005）是孕妇产后肾功能受损加重的危险因素。高尿酸血症（P=0.012,OR=1.006）也是胎儿死亡的危险因素。 结论 妊娠并发肾病综合征患者的胎儿存活率低,其中高尿酸血症是威胁孕妇和胎儿的首要危险因素。     

Pregnancy in patients with IgA nephropathy: a retrospective study for 20 years

Objective To analyze prognosis of pregnancy and kidney disease, and evaluate effects of renal pathology on pregnant outcomes and clinical risk factors of adverse outcomes of pregnancy in IgA nephropathy (IgAN) patients. Methods IgAN patients with more than 20 weeks of pregnancy were included, by retrieving the medical database in Peking Union Medical College Hospital from January 1996 to December 2015. Their detailed information during hospitalization and follow-up was recorded, and outcomes of pregnancy and kidney diseases in IgAN patients were assessed. According to Lee's renal pathological grade system, patients were divided into gradeⅣ&Ⅴ group and below grade Ⅳ group to compare their pregnant prognosis. IgAN patients were divied into fetus survival group and fetus death group according to their pregnancy outcomes. The fetal survival factors were analyzed by single factor and multivariate regression. Results A total of 64 pregnancies in 62 patients were included with a mean age of (30.31±4.05) years. The fetus survival rate was 87.5% and the average gestational periods was (35.41±5.10) weeks (ranging from 20-40 weeks). The incidence of pregnancy-induced hypertension syndrome is 17.2% (11 cases). The preterm birth rate was 24.1% (14 cases) among the live births. Serum creatinine increased in 18 cases (28.1%) during pregnancy with median increment of 38.5 μmol/L, and 72.2% patients completely recovered to the level before pregnancy in the postpartum period of 6 months. The incidence of fetus death (38.1% vs 0.0%, P＜0.01), low birth weight infant (46.2% vs 11.1%, P＜0.05) and pregnancy-induced hypertension syndrome (33.3% vs 11.1%, P＜0.05) in Lee's grade Ⅳ&Ⅴ group was higher than those in below grade Ⅳ group. The serum creatinine, urine protein excretion, renal hypertension before pregnancy and renal segmental glomerular sclerosis were significantly increased in fetus death group as compared with those in fetus survival group (all P＜0.05). Logistic regression showed that in all patients an estimated glomerular filtration rate (eGFR)＜60 ml?min-1?(1.73 m2)-1 (OR=76.978, 95%CI 3.327-1780.939, P=0.007) and renal hypertension (OR=14.464,95%CI 1.245-168.053, P=0.033) before pregnancy were the independent risk factors for fetus death, while multipara was a protective factor (OR=0.063, 95%CI 0.005-0.876, P=0.040). Conclusions The fetus survival and kidney prognosis in IgAN patients are closely related to the severity of clinical and pathological changes before pregnancy. Reduced eGFR and complication of renal hypertension are the independent risk factors for adverse prognosis of pregnancy.     

Value of carnitine palmitoyltransferase 1α expression for the assessment of the degree of renal fibrosis and the progression of chronic kidney disease

Objective To study the relationship between the expression of carnitine palmitoyltransferase 1α (CPT1α) and progression of renal interstitial fibrosis and chronic kidney disease (CKD), and to evaluate the value of CPT1α as a biomarker in pathological diagnosis of renal interstitial fibrosis and CKD. Methods As a retrospective cohort study, information of CKD patients dignosed with tubulointerstitial fibrosis by renal biopsy and receiving follow-up from March 1, 2010 to July 30, 2017 in the Second Affiliated Hospital of Nanjing Medical University were collected. Renal tissues were stained by immunohistochemistry to detect the expression of CPT1α protein and then divided into three groups according to the quartile of proportion of CPT1α positive staining cells, including group Q1(＞67.89%), group Q2(49.84%-67.89%) and group Q3(＜49.84%). The degree of renal interstitial fibrosis was measured by Masson staining and lipid deposition was represented by Bodipy staining. Messenger RNA of CPT1α and collagen as well as other extracellular matrix genes were detected by real time-PCR. Relationships between proportion of CPT1α positive staining cells and renal interstitial fibrosis and renal function were analyzed by linear regression analysis. The relationship between CPT1α positive cell number ratio and renal function progression was measured by Pearson correlation analysis and generalized linear model. The effect of lipid-lowering medicine on renal function of CKD patients was analyzed by paired comparative analysis. Results Ninety patients with CKD were included in this study. Renal interstitial fibrosis and lipid droplets deposition area increased in Q2/Q3 group compared with Q1 group by Masson and Bodipy staining (all P＜0.05). Messenger RNA level of extracellular matrix-related proteins increased in Q2/Q3 group by real time-PCR than those of Q1 group (all P＜0.05). Linear regression analysis showed that fibrosis area was negatively correlated with the proportion of CPT1α positive staining cells (r=-0.309, P＜0.01). The baseline expression of CPT1α in renal issues was negatively related with serum creatinine (Scr) (r=-2.801, P＜0.001), positively related with estimated glomerular filtration rate (eGFR) (r=1.240, P＜0.001). After a medium follow-up of 3.47 years, CPT1α positive cell number ratio was positively correlated with eGFR change rate by Pearson analysis (r=0.220, P=0.038). Paired stratified analysis showed that taking lipid-lowering medicines attenuated the decrease of eGFR in Q2 group and Q3 group but not in Q1 group (both P＜0.05). Conclusions The decline of CPT1α in renal tissues of CKD patients is associated with the increase of Scr, the decrease of eGFR and renal interstitial fibrosis. CPT1α is a promising molecular marker to evaluate the degree of renal fibrosis and the progression of CKD.     

Relationship between interventricular septum thickness and renal prognosis in IgA nephropathy patients

Objective To investigate the relationship between interventricular septum thickness (IVST) and renal prognosis in IgA nephropathy patients. Methods A total of 213 patients with IgA nephropathy proven by biopsy from Department of Nephrology of Shenzhen Second People's Hospital were enrolled in this study, and these participants were divided into normal IVST group (＜11 mm) and higher IVST (≥11 mm) group according to IVST. The demographic characteristics, clinical biochemical indexs, CKD stage and pathologic characteristics in these two groups were compared. Binary logistic regression analysis was used to analyze the influencing factors of eGFR＜60 ml?min-1?(1.73 m2)-1, and Kaplan-Meier survival curve was used to analyze the effect of IVST on renal prognosis. Results Compared with IVST normal group, the patients in IVST higher group were more male sex, older, and had higher level of systolic pressure, Hb, Scr, BUN, UA, 24 h urine protein excretion, urinary protein creatinine ratio, triacylglycerol, total cholesterol, LDL, Serum C3, C4, and had more serious mesangial proliferation, tubular atrophy (all P＜0.05). However, the levels of eGFR and HDL were decreased in IVST higher group (both P＜0.05). There were a significant difference in CKD staging distributions and IgA Lee grade between two groups (both P＜0.01). Spearman and Pearson correlation analysis indicated that IVST was negatively correlated with eGFR and positively correlated with proteinuria level in IgA nephropathy patients. Baseline IVST was an independent risk factor of eGFR＜60 ml?min-1?(1.73 m2)-1 in IgA nephropathy patients. Serum C3, UA and hemoglobin were independent influential factors of eGFR decline (all P＜0.05). Kaplan-Meier survival curve indicated that the renal function was worse in patients with thickened interventricular septum. Conclusion The IgA nephropathy patients with thicker interventricular septum has a poor renal prognosis.     

Levels of bisphenols in patients with chronic kidney disease and their correlation with renal function

Objective To observe the levels of four bisphenols (bisphenol A, B, S and F) and their correlation with renal function in chronic kidney disease (CKD) patients. Methods Patients with CKD were identified according to Kidney Disease: Improving Global Outcomes (KDIGO) criteria. Sixty-three CKD patients and eleven healthy controls were enrolled. CKD patients were further classified as mild renal injury group (CKD stage 1 and 2, n=30), moderate renal injury group (CKD stage 3, n=19) and severe renal injury group (CKD stage 4 and 5, n=14). The levels of four bisphenols in serum were determined by high performance liquid chromatography (HPLC). The correlation between concentrations of four bisphenols and estimated glomerular filtration rate (eGFR) was assessed by Spearman's rank correlation analysis. The associations of four bisphenols with coronary heart disease, diabetes and hypertension in CKD patients were estimated by binary multivariate logistic regression. Results (1) Four bisphenols were not detected in serum of healthy control. In the mild renal injury group the bisphenol A and bisphenol S were not detected, and patients had 5.24 (5.24, 9.38) μg/L bisphenol B and 0.74 (0.74, 0.74) μg/L bisphenol F. In the moderate renal injury group bisphenol S was not detected, and patients had 2.79 (1.01, 4.53) μg/L bisphenol A, 5.24 (5.24, 5.24) μg/L bisphenol B and 0.74 (0.74, 0.74) μg/L bisphenol F. In severe renal injury group patients had 14.30 (7.97, 18.17) μg/L bisphenol A, 0 μg/L bisphenol B, 23.73 (23.73, 136.59) μg/L bisphenol S and 0.74 (0.74, 1.42) μg/L bisphenol F. The levels of bisphenol A and bisphenol S in severe renal injury group were higher than those in the healthy control group, mild renal injury group and moderate renal injury group (all P＜0.05). Bisphenol B and bisphenol F were not statistically different among four groups. (2) Bisphenol A and bisphenol S were negatively correlated with eGFR (r=-0.779, P＜0.001; r=-0.546, P＜0.001). (3) Among CKD patients, bisphenol A was correlated with diabetes (OR=4.951, 95%CI 1.603-15.294, P=0.005), and bisphenol S was correlated with hypertension (OR=4.466, 95%CI 1.575-12.666, P=0.005). Conclusions CKD patients have a variety of bisphenol compounds, especially bisphenol A and bisphenol S. Bisphenol A and bisphenol S have high levels, and their exposures are correlated with renal function.     

Ischemic nephropathy: proteinuria and renal resistance index could suggest if revascularization is recommended

Background: The aim of endovascular therapy in renal artery stenosis (RAS) is to preserve renal function and have a better hypertension control. The purpose of our study was to determine which biochemical and instrumental parameters could predict a better renal outcome in patients with RAS treated with percutaneous transluminal angioplasty and stenting (RPTAS). Methods: We performed an observational study based on 40 patients with RAS who met the following criteria before revascularization: urinary protein excretion of over 250 mg/24 h, normal renal function, and/or mild–moderate renal insufficiency (I, II, and III levels of classification of chronic kidney disease, K-DOQI). Results: Assessment at 12 months after RPTAS showed in 20 patients (Group A) that proteinuria serum creatinine (Scr) and creatinine clearance (CrCl) significantly worsened from the baseline; whereas in 20 patients (Group B) proteinuria remained unchanged and the renal function improved after the procedure. Conclusions: In our study, the decline of renal function after RPTAS is associated with an elevated renal resistance index (RI) in both kidneys (0.83 ± 0.2) and preexisting proteinuria.     

Peritubular capillaries injury and its association with clinical characteristics and long term renal survival in primary malignant nephrosclerosis patients

Objective To analyze the clinic-pathological data and peritubular capillary (PTC) injuries of malignant nephrosclerosis (MN) patients and their correlations with the long term renal survival. Methods This was a retrospective cohort study of 52 MN patients in Peking Union Medical College Hospital from January 2003 to March 2012. Their clinical data and renal biopsy samples were carefully studied. CD34 staining was performed to evaluate the PTC area, using Benign nephrosclerosis (BN, n=17) patients and glomerular minimal lesions (GML, n=19) patients as controls. Multivariate Cox proportional hazard model was used to identify the potential independent risk factors for long term renal survival. Results Fifty-two MN patients were enrolled. The sex ratio of male to female was 12∶1 and the average age was (34.0±8.2) years. The maximum blood pressure (SBP/DBP) was (230.4±25.0)/(156.4±20.6) mmHg, companied with significant loss of eGFR and proteinuria. Glomerular sclerosis index, tubular atrophy and interstitial fibrosis correlated with eGFR and proteinuria(P＜0.05). After aggressive treatment, BP control rate improved significantly (76.9% vs 3.7%, P＜0.01), Scr [(376.4±263.8) μmol/L vs (486.8±375.7) μmol/L, Wilcoxon test, P＜0.01] and proteinuria [(1.10±0.70) g/24 h vs (2.04±1.26) g/24 h, P＜0.01, n=21] also improved. PTC area in MN patients was significantly lower than those in BN patients and GML patients, and it correlated well with Scr (r=-0.553, P=0.001) and eGFR (r=0.476, P=0.004). The median follow-up time was 74 months, the cumulative renal survival rate at 1 year, 5 year and 10 year was 90%, 64% and 23%, respectively. Kaplan-Meier analysis showed that the patients with higher PTC area had longer renal survival time [(114.8±12.4) months vs (63.0±8.3) months, χ2=5.312, P＜0.05]. Univariate Cox proportional hazard model found that unsatisfied BP control, eGFR＜30 ml?min-1?(1.73 m2)-1 upon discharge, lower PTC area, severer tubular-interstitial damage and anemia were associated with poor renal outcome. Multivariate Cox model showed that unsatisfied BP control (RR=3.89, 95% CI 1.75-8.65, P=0.001), eGFR＜30 ml?min-1?(1.73 m2)-1 upon discharge (RR=4.27, 95%CI 1.40-13.09, P=0.011) were independent risk factors for long-term renal survival. Conclusions The correlation between PTC area and renal functions in MN patients are much better than that of classic vascular changes. Unsatisfied BP control and eGFR＜30 ml?min-1?(1.73 m2)-1 upon discharge are independent risk factors for long-term renal survival.     

Clinical significance of phospholipase A2 receptor 1 in patients with idiopathic membranous nephropathy

Objective To explore the role of phospholipase A2 receptor 1 (PLA2R1) in the diagnosis, differential diagnosis and evaluation of idiopathic membranous nephropathy (IMN) in adult patients. Methods A total of 242 renal disease patients diagnosed by renal biopsy from March 2015 to January 2016 were enrolled, consisting of 90 IMN, 20 secondary membranous nephropathy (SMN), 82 IgA nephropathy (IgAN), 30 minimal changed disease (MCD), 16 focal segmental glomerulosclerosis (FSGS) and 4 membranoproliferative glomerulonephritis (MPGN). Their clinical data including age, sex, serum creatinine (Scr), serum albumin and 24 h urinary protein were collected. Serum PLA2R1 was measured by enzyme linked immunosorbent assay. PLA2R and IgG subclasses in glomeruli were detected by indirect immunofluorescence assay. The positive rate of serum PLA2R1 among those groups and its correlation with clinical-pathological parameters were analyzed. Results Compared with IMN patients, SMN, MCD and FSGS patients were younger (all P＜0.01); IgAN patients were younger and had higher serum albumin and lower 24 h proteinuria (all P＜0.001); MPGN patients had higher Scr (all P＜0.01). The positive rate of serum PLA2R1 was 75.6% in IMN patients, while it was 0.0% in non-IMN patients. The distribution between serum PLA2R1 and pathological diagnosis had difference (P＜0.001), their positive coincidence rate was 100%, negative coincidence rate was 87.4%, total coincidence rate was 90.9% and their consistency was well (Kappa=0.795, P＜0.001). Among IgG subtype comparisons between IMN patients and SMN patients in the glomeruli, only moderate or more positive IgG4 had statistical differences (82.2% vs 5.0%, P＜0.001); the positive rate of glomerular PLA2R1 was 41.1% in IMN patients, higher than 10.0% in SMN patients (P=0.009); positive PLA2R1 with moderate or more positive IgG4 in glomeruli in IMN patients was more than that in SMN patients (40.0% vs 0.0%, P＜0.001), which could improve the diagnostic specificity of IMN. In IMN patients serum PLA2R1 and glomerular PLA2R1 had statistical differences (P＜0.001). Spearman rank correlation analysis showed that serum PLA2R1 of IMN patients positively correlated with 24 h proteinuria (r=0.315, P=0.002), negatively correlated with serum albumin (r=-0.228, P=0.030) and didn't correlate with Scr (r=0.199, P=0.059). Conclusions Serum PLA2R can be used as the specific indicator for diagnosis, differential diagnosis of IMN and to reflect the severity of IMN in patients.     

Renal ultrasound elastography can reflect clinical-pathological changes in chronic kidney disease patients

Objective To analyze how is the elastography of renal tissue correlated to clinical biochemical indexes and pathological changes in patients with chronic kidney disease (CKD), and to explore the potential of renal elastography to become a new noninvasive method available for the dynamic monitoring of renal disease progression, as well as its efficacy assessment and prognosis evaluation. Methods Patients admitted to the department of nephrology of the First Affiliated Hospital of China Medical University and received renal biopsy from August 2014 to January 2015 were selected. One hundred and thirteen cases of CKD patients, 61 males and 52 females were enrolled, including 23 cases of IgA nephropathy, 39 cases of membranous nephropathy, 15 cases of minimal change nephropathy and 7 cases of focal segmental glomerulosclerosis. The Young modulus of renal cortex and medulla (YMcortex and YMmedulla) were detected by Aix Plorer type full digital color Doppler ultrasound. The correlations between the YMs and clinical biochemical indicators in blood and urine, and the difference of YMs among different pathological changes in patients with CKD were analyzed by statistics. Results The YMcortex and YMmedulla in CKD patients were higher than those in the control group (all P＜0.05); and with the progression of CKD, the YMcortex and YMmedulla gradually increased. The YMcortex in CKD G5 patients was higher than that in CKD G1-3 patients (all P＜0.05). The YMmedulla in CKD G3-5 patients was higher than that in CKD G1-2 patients (all P＜0.05). The YMcortex was correlated with systolic pressure, serum creatinine, cystatin C, serum albumin, serum phosphorus, calcium and phosphorus product, uric acid, intact parathyroid hormone (iPTH), urinary NAG, estimate glomerular filtration rate (eGFR) and hemoglobin (all P＜0.05). The YMmedulla was correlated with systolic pressure, serum creatinine, serum albumin, uric acid, iPTH, urine microalbumin (MA), urinary NAG and hemoglobin (all P＜0.05). Serum cystatin C (β=0.485, P=0.018) and uric acid (β=0.418, P=0.039) were independently correlated with the YMcortex. Serum creatinine (β=0.380, P=0.019), uric acid (β=0.482, P=0.004) and smoking (β=0.337, P=0.009) were independently correlated with YMmedulla. The YMcortex and YMmedulla in different pathological types were statistically significant (P＜0.001, P=0.003). The YMcortex and YMmedulla in patients with membranous nephropathy and IgA nephropathy were higher than those in the patients with minimal change nephropathy (all P＜0.05). The YMmedulla in patients with focal segmental glomerulosclerosis was higher than that in the patients with minimal change nephropathy (P＜0.05). The YMcortex in the patients with phases Ⅳ and Ⅴ based on the Lee grading system of IgA nephropathy was higher than that in the patients with phases Ⅱ and Ⅲ (P＜0.05). According the Oxford classification for IgA nephropathy, the YMcortex and YMmedulla in the T1 and T2 patients were higher than those in the T0 patients (P＜0.05). The YMcortex and YMmedulla showed no statistically significant differences among different stages of membranous nephropathy. Conclusions The YMcortex and YMmedulla are associated with the progress of renal insufficiency, which may become new indicators for determining CKD progression. The renal ultrasound elastography may become a new non-invasive method for early diagnosing CKD, dynamic monitoring disease progression, and assessing efficacy and prognosis.