Nephropathy in Indian patients with non-insulin-dependent diabetes in the young

In 85 patients diagnosed as having non-insulin-dependent diabetes in the young (NIDDY), 6 were found to have nephropathy. The duration of diabetes ranged from 2 to 17 yr; 5 of the 6 patients had retinopathy as evidenced by fluoroscein angiography (3 with proliferative changes). All 6 patients had a 24-h urinary protein excretion greater than 0.5 g and a glomerular filtration rate less than 80 ml/min. Serum beta 2-microglobulin levels were increased in all 6 patients, while only 3 had increased serum creatinine levels.     

Early Diabetic Nephropathy: A complication of reduced insulin sensitivity in type 1 diabetes

OBJECTIVE

Diabetic nephropathy (DN) is a major cause of mortality in type 1 diabetes. Reduced insulin sensitivity is a well-documented component of type 1 diabetes. We hypothesized that baseline insulin sensitivity would predict development of DN over 6 years.

RESEARCH DESIGN AND METHODS

We assessed the relationship between insulin sensitivity at baseline and development of early phenotypes of DN—microalbuminuria (albumin-creatinine ratio [ACR] ≥30 mg/g) and rapid renal function decline (glomerular filtration rate [GFR] loss >3 mL/min/1.73 m² per year)—with three Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equations over 6 years. Subjects with diabetes (n = 449) and without diabetes (n = 565) in the Coronary Artery Calcification in Type 1 Diabetes study had an estimated insulin sensitivity index (ISI) at baseline and 6-year follow-up.

RESULTS

The ISI was lower in subjects with diabetes than in those without diabetes (P < 0.0001). A higher ISI at baseline predicted a lower odds of developing an ACR ≥30 mg/g (odds ratio 0.65 [95% CI 0.49–0.85], P = 0.003) univariately and after adjusting for HbA_1c (0.69 [0.51–0.93], P = 0.01). A higher ISI at baseline conferred protection from a rapid decline of GFR as assessed by CKD-EPI cystatin C (0.77 [0.64–0.92], P = 0.004) and remained significant after adjusting for HbA_1c and age (0.80 [0.67–0.97], P = 0.02). We found no relation between ISI and rapid GFR decline estimated by CKD-EPI creatinine (P = 0.38) or CKD-EPI combined cystatin C and creatinine (P = 0.50).

CONCLUSIONS

Over 6 years, a higher ISI independently predicts a lower odds of developing microalbuminuria and rapid GFR decline as estimated with cystatin C, suggesting a relationship between insulin sensitivity and early phenotypes of DN.Diabetic nephropathy (DN) is a common and serious complication of diabetes. Its incidence is rising rapidly (1), and it is the most common cause of end-stage renal disease in the U.S. and Europe (2). The 2011 U.S. Renal Data System showed that DN accounted for 44.5% of all cases of end-stage renal disease in 2009 (3). Despite improvements in the outlook of this complication in past decades, it continues to be one of the major causes of morbidity and mortality in type 1 diabetes (4,5). DN is an important risk factor for coronary artery disease (6–8) and overall mortality (6,9). These findings highlight the need for improved methods of identifying persons at high risk for DN (10).The role of insulin sensitivity in the development and progression of macro- (7,11,12) and microvascular complications (12,13) in type 1 diabetes is increasingly recognized. Reduced insulin sensitivity also is a plausible mechanism linking renal disease with excess mortality in type 1 diabetes. Historically, when glycemic control is poor, reduced insulin sensitivity was believed to be directly related to body weight and HbA_1c (14,15), but more recent data suggest that reduced insulin sensitivity cannot simply be explained by weight or poor glycemic control. In fact, reduced insulin sensitivity has been documented in type 1 diabetic subjects with normal BMI and HbA_1c compared with nondiabetic individuals (16). The Coronary Artery Calcification in Type 1 Diabetes (CACTI) longitudinal cohort study of adults with type 1 diabetes investigated the determinants of early and accelerated atherosclerosis and found that insulin sensitivity independently predicted coronary artery calcification (17,18). Reduced insulin sensitivity has also been shown to predict diabetic retinopathy, neuropathy, and nephropathy in subjects with type 1 diabetes (13).Despite advances in the estimation of insulin sensitivity (insulin sensitivity index [ISI]) (19) and glomerular filtration rate (GFR) (20), research in the association of insulin sensitivity with DN has been limited since the Pittsburgh Epidemiology of Diabetes Complications (EDC) cohort showed more than a decade ago that the estimated glucose disposal rate (eGDR) predicts overt nephropathy (13). To readdress this relationship with contemporary data and estimating equations, we hypothesized that higher insulin sensitivity measured by ISI at baseline would be associated with decreased odds of developing two early phenotypes of DN—microalbuminuria (albumin-creatinine ratio [ACR] ≥30 mg/g) and rapid renal function decline (GFR loss >3 mL/min/1.73 m² per year) (21–23)—calculated by the three Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equations (20) over 6 years in the CACTI study.     

2型糖尿病合并IgA肾病与糖尿病肾病患者的临床分析

目的：分析2型糖尿病合并IgA肾病与2型糖尿病合并糖尿病肾病患者的临床特点,鉴别诊断要点。方法：回顾分析18例2型糖尿病合并IgA肾病与15例2型糖尿病合并糖尿病肾病患者的临床资料。结果：2型糖尿病合并IgA肾病患者糖尿病病史（10.72±18.66个月）明显短于糖尿病肾病患者（58.73±71.12个月）,P〈0.05。IgA肾病组在肾活检时血肌酐升高的比例（5.56%）明显低于糖尿病肾病组（46.67%）,P〈0.05,伴有血尿的患者（61.11%）明显多于糖尿病肾病组（20.00%）,P〈0.05。IgA肾病组总胆红素、丙氨酸氨基转移酶、血清免疫球蛋白A、血清免疫球蛋白G、血钙明显高于糖尿病肾病组（分别为13.28±4.14μmol.L^-1比9.95±4.87μmol.L^-1、34.22±18.11U.L^-1比19.73±16.04U.L^-1;4.00±2.16g.L^-1比2.11±0.86g.L^-1;12.47±4.76g.L^-1比9.04±2.41g.L^-1和2.37±0.17mmol.L^-1比2.22±0.20mmol.L^-1）。IgA肾病组血尿素氮、血肌酐、50%补体溶血单位、随机尿白蛋白/肌酐比值、24h尿蛋白显著低于糖尿病肾病组[分别为5.86±1.59mmol.L^-1比10.76±5.89mmol.L^-1;82.72±23.76μmol.L^-1比185.20±107.19μmol.L^-1;50.51±5.80IU.mL^-1比55.37±6.17IU.mL^-1;959.50±395.00μg.（mgCr）^-1比3193.85±2085.00μg.（mgCr）^-1和2.22±2.13g.（24h）^-1比4.69±2.92g.（24h）^-1]。两组血糖、血脂均无统计学差异。IgA肾病患者荧光眼底血管造影和肌电图检查未见异常,糖尿病肾病组有2例糖尿病视网膜病变和3例糖尿病周围神经病变。结论：2型糖尿病合并IgA肾病的患者尿检异常出现前糖尿病病史大多短于5年,血尿、血清免疫球蛋白A升高多见,尿检异常出现时无糖尿病视网膜病变或周围神经病变。     

Idiopathic Membranous Nephropathy

The clinical and histopathological features of 37 patients withidiopathic membranous nephropathy are presented. Males werefour times as commonly affected as females and the age at presentationranged from nine to 70 years. The period of observation variedfrom three months to 23 years. Twenty-eight patients (76 percent)presented with the nephrotic syndrome and nine patients (24per cent) presented with non-nephrotic proteinuria. At the endof the study, of the patients presenting with the nephroticsyndrome, seven (25 per cent) were in remission, seven (25 percent) remained nephrotic, nine (32 per cent) showed only proteinuriaand five (18 per cent) were dead or on dialysis. Altogethereight patients (28 per cent) developed renal failure. The ninepatients who presented with non-nephrotic proteinuria appearedto do better, and none developed renal failure. The occurrence of spontaneous remission makes assessment ofbenefit from immunosuppressivet herapy difficult. However, analysisof our data and a review of the literature suggest that in thiscondition oral prednisone, cyclophosphamide and azathioprinehave no significant therapeutic properties. Histological assessment confirmed the occurrence of mild (Grade1) changes in patients biopsied soon after presentation, andtubular atrophy increased with the duration of illness. Immunofluorescenceconfirmed deposition of mainly IgG and complement. Repeat biopsiesin 14 patients showed no histological improvement and remissionwas not accompanied by resolution of histological abnormalities.     

Arterial stiffness and vascular complications in patients with type 1 diabetes: The Finnish Diabetic Nephropathy (FinnDiane) Study

Abstract

Introduction/aims. While patients with type 1 diabetes (T1D) are known to suffer from early cardiovascular disease (CVD), we examined associations between arterial stiffness and diabetic complications in a large patient group with T1D.

Methods. This study included 807 subjects (622 T1D and 185 healthy volunteers (age 40.6 ± 0.7 versus 41.6 ± 1.2 years; P = NS)). Arterial stiffness was measured by pulse wave analysis from each participant. Furthermore, information on diabetic retinopathy, nephropathy, and CVD was collected. The renal status was verified from at least two out of three urine collections.

Results. Patients with T1D without signs of diabetic nephropathy had stiffer arteries measured as the augmentation index (AIx) than age-matched control subjects (17.3% ± 0.6% versus 10.0% ± 1.2%; P < 0.001). Moreover, AIx (OR 1.08; 95% CI 1.03–1.13; P = 0.002) was associated with diabetic laser-treated retinopathy in patients with normoalbuminuria in a multivariate logistic regression analysis. The same was true for AIx and diabetic nephropathy (1.04 (1.01–1.08); P = 0.004) as well as AIx and CVD (1.06 (1.00–1.12); P = 0.01) in patients with T1D.

Conclusions. Arterial stiffness was associated with microvascular and macrovascular complications in patients with T1D.     

血清淀粉样蛋白A与2型糖尿病肾病的相关性

目的探讨血清淀粉样蛋白A（serum amyloid A,SAA）水平在2型糖尿病（T2DM）伴发糖尿病肾病（DN）中的意义。方法根据尿白蛋白排泄率（UAER）将102例2型糖尿病（T2DM）患者分为单纯糖尿病组（SDM组）、早期糖尿病肾病组（EDN组）和临床糖尿病肾病组（CDN组）,30名本院健康体检者作为对照组,应用免疫透射比浊法测定血清SAA,将组间的SAA进行统计学比较,并进行相关分析。结果各糖尿病组血清SAA水平与对照组比较均具有统计学差异（P〈0．05）,EDN、CDN组显著高于SDM组（P〈0．05）,CDN组与EDN组相比亦明显升高（P〈0．05）。相关分析显示SAA与UAER呈显著正相关（r=0．536,P〈0．01）。结论SAA水平在T2DM组和并发DN组中随着UAER的增加而升高,两者之间关系密切,提示炎症反应可能在DN的发病机制中起着重要的作用。     

足细胞损伤对IgA肾病肾小球硬化的作用

目的：研讨IgA肾病患者肾小球足细胞损伤对IgA肾病进展的作用。方法：44例经肾穿刺活检明确诊断的IgA肾病患者，采用免疫组织化学技术定量肾组织病理并借助足细胞表面特异性标记物Wilms′肿瘤蛋白（WT1）对肾小球足细胞进行准确的密度定量分析。结果：WT1表达在正常肾脏肾小球的脏层上皮细胞，IgA肾病患者随着病变加重，硬化肾小球增加，足细胞数目也明显减少（P〈0.01），肾小球中的WT1表达与尿蛋白定量无明显相关性，但与血清肌酐水平呈显著正相关（r=0.541，P〈0.01）。结论：肾小球足细胞损伤可能是影响IgA肾病进展的因素之一。     

马兜铃酸肾病研究新进展

近年来,有关中草药不良反应的文献报道逐年增多,国外10余年前就有人提出“中草药肾病”的概念[1]。2001年美国FDA宣布禁止含关木通、马兜铃、青木香等10多种中药进口,在国际上造成很大的影响。因此,深入探讨中草药的肾脏毒性作用,对指导临床用药和中医药走向世界都是有益。1“中草药肾病”说的来由1993年比利时Vanherweghem[1]首先发现并报告,服用减肥药物者中出现多例急性肾间质纤维化、肾功能不全患者,进一步调查发现是减肥药中的广防己所致,并提出“中草药肾病(ChineseHerbNepropathy,CHN)”的概念。后经调查证实,原减肥药处方中的汉…     

尿微量白蛋白在糖尿病和高血压肾病早期诊断中的应用

目的探讨尿微量白蛋白(UMA)在糖尿病肾病(DN)和高血压肾病早期的诊断价值。方法将研究对象分为糖尿病无合并症组、糖尿病肾病血压正常组、糖尿病肾病高血压组和普通高血压病组,测定UMA和血BUN、Cr含量。结果 DN和高血压肾病患者UMA含量和阳性率明显增高,且与病程和年龄密切相关,r值分别为0.436-0.663和0.415-0.832,病程越长,年龄越大,增高越显著(P0.05-P0.001),而与性别无关(P0.05);随高血压分级的增加,UMA含量和阳性率明显增加;DM各组Cr和BUN含量和阳性率也升高,反映DN和高血压肾病指标的敏感性依次为UMACrBUN。结论 UMA检测对DM和高血压患者的早期肾损伤有预测价值,动态监测有助于DN和高血压肾病的早期诊断。     

POEMS综合征相关性肾病

病史及临床表现：患者，男，47岁，因消瘦、色素沉着3年，四肢麻木、性功能减退2年，双下肢水肿半年入院。查体：全身皮肤色素沉着，浅表淋巴结、颌下腺、甲状腺及肝脏肿大，四肢末端痛觉减退，双手、足杵状指(趾)。实验室及病理检查：尿蛋白(2 )；血清免疫球蛋白电泳检查示：IgA-λ型M蛋白血症。骨髓穿刺、活检示浆细胞占5．5％，可见异型的浆细胞。肾脏活检：光镜下见肾小球系膜细胞及基质增生，少数毛细血管基膜增厚呈节段性双轨；电镜检查示基质增生，毛细血管内皮空泡样变性，内皮下间隙增宽并见致密复合物沉积。治疗及随访：确诊POEMS综合征后，即给予强的松治疗。随访10月后患者症状、体征及实验室检查结果明显好转。结论：POEMS综合征相关性肾病临床症状的轻重与病理变化的严重程度无相关关系，临床上易被忽视；组织学上以膜增殖性肾小球肾炎样病变为主；其发病机理推测与毛细血管内皮细胞的慢性损伤有关；治疗上对皮质类固醇治疗反应良好。     

Prognostic Indicators in Idiopathic IgA Mesangial Nephropathy

Univariate survivorship analysis of a cohort of 365 patientswith idiopathic IgA mesangial nephropathy and at least one yearof further observation since the apparent onset (mean=7.79±6.19years; median=6.16 years) has been performed. Observations forat least one year (mean=5.05±3.66; median=4.08 years)after biopsy was available for 292 of these. One immunohistological, four clinical, and six histologicalfeatures were associated with increased risk of developing renalfailure: (i) older at onset; (ii) no history of recurrent macroscopic haematuria; (iii) proteinuria of more than 1 g/day; (iv)arterial hypertension at the time of biopsy; (v) extent of glomerularobsolescence; (vi) extent of segmental glomerulosclerosis; (vii)presence of interstitial fibrosis; (viii) presence of diffuseintracapillary proliferation; (ix) presence of extracapillaryproliferation; (x) presence of segmental thickening of glomerularbasement membrane; (xi) extension of IgA deposits to the peripheralcapillary loops shown by Immunofluorescence. Only features (iii),(v), (vii) and (xi) proved to be independent prognostic indicatorsin the multivariate survivorship analysis (Cox regression model).     

IgA肾病小管间质病理改变的意义

采用微机图像处理系统对５２例ＩｇＡ肾病的小管间质病理形态、间质淋巴细胞亚群和单核细胞分布进行定量分析。结果：肾活检和随访中的血清肌酐浓度与皮质间面积密度、间质胶原面积密度、小管毛细血管距离、间质ＣＤ＾－４，ＣＤ＾－６及单细胞数密度呈显著正相关，与近曲小管上波细胞面积密度、球后毛细血管数的面积密度呈显著负相关。     

全面认识肾脏疾病实验室诊断的范畴与意义

传统的肾功能检查包括:①尿常规各成分检查;②反映肾小球滤过功能的血尿素氮、肌酐;③肾小管功能包括尿糖、尿氨基酸、尿pH;④稀释和浓缩功能检查;⑤尿中与肾小管特殊有关的蛋白如β鄄微球蛋白测定等。上述各种检查依然是临床发现及判断肾脏病变严重程度等的主要内容。然而,随着人们对肾脏疾病防治的进一步重视,加上对导致肾脏病的各种发病机制的进一步认识,对于肾脏疾病的诊断当然要提出更高的要求。另外,由于肾脏疾病的进展性质,又要求对肾脏损伤的趋势,即可以预测病变进展以及进展趋势的各种指标进行了解。在肾脏疾病过程中,特别在终末…