切换至 "中华医学电子期刊资源库"

中华肾病研究电子杂志 ›› 2016, Vol. 05 ›› Issue (04) : 145 -151. doi: 10.3877/cma.j.issn.2095-3216.2016.04.001

所属专题: 文献

述评

加强对正常蛋白尿糖尿病肾脏疾病的认识
孙林1,(), 陈超1   
  1. 1. 410011 中南大学湘雅二医院肾脏病研究所、湘雅二医院肾内科
  • 收稿日期:2016-05-21 出版日期:2016-08-28
  • 通信作者: 孙林
  • 基金资助:
    国家自然科学基金(81270812,81470960)

Strengthening the understanding of normoalbuminuric diabetic kidney disease

Lin Sun1,(), Chao Chen1   

  1. 1. Department of Nephrology, Institute of Kidney Disease, Second Xiangya Hospital Affiliated to Central South University, Changsha, Hunan 410011, China
  • Received:2016-05-21 Published:2016-08-28
  • Corresponding author: Lin Sun
  • About author:
    Corresponding author: Sun Lin, Email:
引用本文:

孙林, 陈超. 加强对正常蛋白尿糖尿病肾脏疾病的认识[J]. 中华肾病研究电子杂志, 2016, 05(04): 145-151.

Lin Sun, Chao Chen. Strengthening the understanding of normoalbuminuric diabetic kidney disease[J]. Chinese Journal of Kidney Disease Investigation(Electronic Edition), 2016, 05(04): 145-151.

糖尿病肾脏疾病(DKD)是导致终末期肾脏病(ESRD)的主要原因,早期及时诊断对防治DKD进展非常重要。以往DKD临床诊断多注重尿白蛋白排泄率(UAER),并以此作为诊断与临床分期的重要依据。实际上许多糖尿病(DM)有时表现为无临床诊断价值的蛋白尿,而以肾功能减退为突出肾脏受累表现,即正常蛋白尿糖尿病肾脏疾病(NADKD),或称无蛋白尿糖尿病肾病(nonalbuminuric diabetic nephropathy),及糖尿病无蛋白尿肾功能不全(nonalbuminuric renal impairment in diabetes)。本文结合国内外研究现状,从流行病学、病理、临床特征、诊断及治疗等方面对NADKD进行了描述,以翼引起同行重视。

Diabetic kidney disease (DKD) is a primary cause for end-stage renal disease (ESRD). Early diagnosis is very important for preventing the progression of DKD. Assessment of urinary albumin excretion rate (UAER) played a key role in the diagnosis and clinical stages of patients with DKD. Actually, many diabetic mellitus (DM) patients sometimes showed nonalbuminuric renal insufficiency, which was named normoalbuminuric diabetic kidney disease (NADKD), nonalbuminuric diabetic nephropathy, or nonalbuminuric renal impairment in diabetes. In this article, the authors discussed NADKD in epidemiology, pathology, clinical features, diagnosis and treatment, etc, hoping to attract attention from colleagues in nephrology.

[20]
Penno G,Solini A,Bonora E, et al. Clinical significance of nonalbuminuric renal impairment in type 2 diabetes[J]. J Hypertens, 2011, 29(9): 1802-1809.
[21]
Kramer HJ,Nguyen QD,Curhan G, et al. Renal insufficiency in the absence of albuminuria and retinopathy among adults with type 2 diabetes mellitus[J]. JAMA, 2003, 289(24): 3273-3277.
[22]
Penno G,Solini A,Zoppini G, et al. Rate and determinants of association between advanced retinopathy and chronic kidney disease in patients with type 2 diabetes: the Renal Insufficiency And Cardiovascular Events (RIACE) Italian multicenter study[J]. Diabetes Care, 2012, 35(11): 2317-2323.
[23]
New JP,Middleton RJ,Klebe B, et al. Assessing the prevalence, monitoring and management of chronic kidney disease in patients with diabetes compared with those without diabetes in general practice[J]. Diabet Med, 2007, 24(4): 364-369.
[24]
Boronat M,Garcia-Canton C,Quevedo V, et al. Non-albuminuric renal disease among subjects with advanced stages of chronic kidney failure related to type 2 diabetes mellitus[J]. Ren Fail, 2014, 36(2): 166-170.
[25]
Araki S,Haneda M,Sugimoto T, et al. Factors associated with frequent remission of microalbuminuria in patients with type 2 diabetes[J]. Diabetes, 2005, 54(10): 2983-2987.
[26]
Molitch ME,Steffes M,Sun W, et al. Development and progression of renal insufficiency with and without albuminuria in adults with type 1 diabetes in the diabetes control and complications trial and the epidemiology of diabetes interventions and complications study[J]. Diabetes Care, 2010, 33(7): 1536-1543.
[27]
Lane PH,Steffes MW,Mauer SM. Glomerular structure in IDDM women with low glomerular filtration rate and normal urinary albumin excretion[J]. Diabetes, 1992, 41(5): 581-586.
[28]
De Cosmo S,Lamacchia O,Pacilli A, et al. Normoalbuminuric renal impairment and all-cause mortality in type 2 diabetes mellitus[J]. Acta Diabetol, 2014, 51(4): 687-689.
[29]
Kamijo-Ikemori A,Sugaya T,Yasuda T, et al. Clinical significance of urinary liver-type fatty acid-binding protein in diabetic nephropathy of type 2 diabetic patients[J]. Diabetes Care, 2011, 34(3): 691-696.
[30]
Shimizu M,Furuichi K,Yokoyama H, et al. Kidney lesions in diabetic patients with normoalbuminuric renal insufficiency[J]. Clin Exp Nephrol, 2014, 18(2): 305-312.
[31]
Araki S,Haneda M,Sugimoto T, et al. Polymorphisms of the protein kinase C-beta gene (PRKCB1) accelerate kidney disease in type 2 diabetes without overt proteinuria[J]. Diabetes Care, 2006, 29(4): 864-868.
[32]
MacIsaac RJ,Panagiotopoulos S,McNeil KJ, et al. Is nonalbuminuric renal insufficiency in type 2 diabetes related to an increase in intrarenal vascular disease?[J]. Diabetes Care, 2006, 29(7): 1560-1566.
[33]
Mattock MB,Barnes DJ,Viberti G, et al. Microalbuminuria and coronary heart disease in NIDDM: an incidence study[J]. Diabetes, 1998, 47(11): 1786-1792.
[34]
Yagil C,Barak A,Ben-Dor D, et al. Nonproteinuric diabetes-associated nephropathy in the Cohen rat model of type 2 diabetes[J]. Diabetes, 2005, 54(5): 1487-1496.
[35]
Ekinci EI,Jerums G,Skene A, et al. Renal structure in normoalbuminuric and albuminuric patients with type 2 diabetes and impaired renal function[J]. Diabetes Care, 2013, 36(11): 3620-3626.
[36]
An JH,Cho YM,Yu HG, et al. The clinical characteristics of normoalbuminuric renal insufficiency in Korean type 2 diabetic patients: a possible early stage renal complication[J]. J Korean Med Sci, 2009, 24 Suppl: S75-S81.
[37]
Ruggenenti P,Fassi A,Ilieva AP, et al. Preventing microalbuminuria in type 2 diabetes[J]. N Engl J Med, 2004, 351(19): 1941-1951.
[38]
Porrini E,Ruggenenti P,Mogensen CE, et al. Non-proteinuric pathways in loss of renal function in patients with type 2 diabetes[J]. Lancet Diabetes Endocrinol, 2015, 3(5): 382-391.
[39]
Neugarten J,Acharya A,Silbiger SR. Effect of gender on the progression of nondiabetic renal disease: a meta-analysis[J]. J Am Soc Nephrol, 2000, 11(2): 319-329.
[40]
Sun L,Kanwar YS. Relevance of TNF-alpha in the context of other inflammatory cytokines in the progression of diabetic nephropathy[J]. Kidney Int, 2015, 88(4): 662-665.
[41]
Perkins BA,Krolewski AS. Early nephropathy in type 1 diabetes: the importance of early renal function decline[J]. Curr Opin Nephrol Hypertens, 2009, 18(3): 233-240.
[42]
Niewczas MA,Ficociello LH,Johnson AC, et al. Serum concentrations of markers of TNFalpha and Fas-mediated pathways and renal function in nonproteinuric patients with type 1 diabetes[J]. Clin J Am Soc Nephrol, 2009, 4(1): 62-70.
[43]
Onuigbo MA. Syndrome of rapid-onset end-stage renal disease: a new unrecognized pattern of CKD progression to ESRD[J]. Ren Fail, 2010, 32(8): 954-958.
[44]
Onuigbo MA,Agbasi N. Diabetic nephropathy and CKD-analysis of individual patient serum creatinine trajectories: a forgotten diagnostic methodology for diabetic CKD prognostication and prediction[J]. J Clin Med, 2015, 4(7): 1348-1368.
[45]
Shimizu M,Furuichi K,Toyama T, et al. Long-term outcomes of Japanese type 2 diabetic patients with biopsy-proven diabetic nephropathy[J]. Diabetes Care, 2013, 36(11): 3655-3662.
[46]
Perkins BA,Ficociello LH,Ostrander BE, et al. Microalbuminuria and the risk for early progressive renal function decline in type 1 diabetes[J]. J Am Soc Nephrol, 2007, 18(4): 1353-1361.
[47]
Ruggenenti P,Porrini E,Motterlini N, et al. Measurable urinary albumin predicts cardiovascular risk among normoalbuminuric patients with type 2 diabetes[J]. J Am Soc Nephrol, 2012, 23(10): 1717-1724.
[48]
Levey AS,Cattran D,Friedman A, et al. Proteinuria as a surrogate outcome in CKD: report of a scientific workshop sponsored by the National Kidney Foundation and the US Food and Drug Administration[J]. Am J Kidney Dis, 2009, 54(2): 205-226.
[49]
Penno G,Solini A,Zoppini G, et al. Independent correlates of urinary albumin excretion within the normoalbuminuric range in patients with type 2 diabetes: The Renal Insufficiency And Cardiovascular Events (RIACE) Italian Multicentre Study[J]. Acta Diabetol, 2015, 52(5): 971-981.
[1]
Xiao L,Wang M,Yang S, et al. A glimpse of the pathogenetic mechanisms of Wnt/beta-catenin signaling in diabetic nephropathy[J]. Biomed Res Int, 2013, 2013: 987064.
[2]
Kwak SH,Park KS. Genetic studies on diabetic microvascular complications: focusing on genome-wide association studies[J]. Endocrinol Metab (Seoul), 2015, 30(2): 147-158.
[3]
Xu X,Xiao L,Xiao P, et al. A glimpse of matrix metalloproteinases in diabetic nephropathy[J]. Curr Med Chem, 2014, 21(28): 3244-3260.
[50]
de Carvalho JA,Tatsch E,Hausen BS, et al. Urinary kidney injury molecule-1 and neutrophil gelatinase-associated lipocalin as indicators of tubular damage in normoalbuminuric patients with type 2 diabetes[J]. Clin Biochem, 2016, 49(3): 232-236.
[51]
Alter ML,Kretschmer A,Von Websky K, et al. Early urinary and plasma biomarkers for experimental diabetic nephropathy[J]. Clin Lab, 2012, 58(7-8): 659-671.
[52]
National Kidney Foundation. K/DOQI clinical practice guidelines for chronic kidney disease: evaluation, classification, and stratification[J]. Am J Kidney Dis, 2002, 39(2 Suppl 1): S1-S266.
[4]
KDOQI Work Group. KDOQI clinical practice guidelines and clinical practice recommendations for diabetes and chronic kidney disease[J]. Am J Kidney Dis, 2007, 49(2 Suppl 2): S12-S154.
[5]
Giordano AL,Siegel HI,Rosenblatt JS. Nuclear estrogen receptor binding in the preoptic area and hypothalamus of pregnancy-terminated rats: correlation with the onset of maternal behavior[J]. Neuroendocrinology, 1989, 50(3): 248-258.
[6]
Tsalamandris C,Allen TJ,Gilbert RE, et al. Progressive decline in renal function in diabetic patients with and without albuminuria[J]. Diabetes, 1994, 43(5): 649-655.
[53]
Levey AS,Bosch JP,Lewis JB, et al. A more accurate method to estimate glomerular filtration rate from serum creatinine: a new prediction equation. Modification of Diet in Renal Disease Study Group[J]. Ann Intern Med, 1999, 130(6): 461-470.
[54]
Cockcroft DW,Gault MH. Prediction of creatinine clearance from serum creatinine[J]. Nephron, 1976, 16(1): 31-41.
[55]
Caramori ML,Fioretto P,Mauer M. Low glomerular filtration rate in normoalbuminuric type 1 diabetic patients: an indicator of more advanced glomerular lesions[J]. Diabetes, 2003, 52(4): 1036-1040.
[56]
Brenner BM,Cooper ME,de Zeeuw D, et al. Effects of losartan on renal and cardiovascular outcomes in patients with type 2 diabetes and nephropathy[J]. N Engl J Med, 2001, 345(12): 861-869.
[57]
Lewis EJ,Hunsicker LG,Clarke WR, et al. Renoprotective effect of the angiotensin-receptor antagonist irbesartan in patients with nephropathy due to type 2 diabetes[J]. N Engl J Med, 2001, 345(12): 851-860.
[58]
Satirapoj B,Kaewput W,Supasyndh O, et al. Effect of sulodexide on urinary biomarkers of kidney injury in normoalbuminuric type 2 diabetes: a randomized controlled trial[J]. J Diabetes Res, 2015, 2015: 172038.
[7]
MacIsaac RJ,Tsalamandris C,Panagiotopoulos S, et al. Nonalbuminuric renal insufficiency in type 2 diabetes[J]. Diabetes Care, 2004, 27(1): 195-200.
[8]
Lacquaniti A,Donato V,Pintaudi B, et al. " Normoalbuminuric" diabetic nephropathy: tubular damage and NGAL[J]. Acta Diabetol, 2013, 50(6): 935-942.
[9]
Mottl AK,Kwon KS,Mauer M, et al. Normoalbuminuric diabetic kidney disease in the U. S. population[J]. J Diabetes Complications, 2013, 27(2): 123-127.
[10]
Macisaac RJ,Jerums G. Diabetic kidney disease with and without albuminuria[J]. Curr Opin Nephrol Hypertens, 2011, 20(3): 246-257.
[11]
American Diabetes Association. Standards of medical care in diabetes-2015 abridged for primary care providers[J]. Clin Diabetes, 2015, 33(2): 97-111.
[12]
Zelmanovitz T,Gross JL,Oliveira JR, et al. The receiver operating characteristics curve in the evaluation of a random urine specimen as a screening test for diabetic nephropathy[J]. Diabetes Care, 1997, 20(4): 516-519.
[13]
Dwyer JP,Parving HH,Hunsicker LG, et al. Renal Dysfunction in the presence of normoalbuminuria in type 2 diabetes: results from the DEMAND Study[J]. Cardiorenal Med, 2012, 2(1): 1-10.
[14]
Kramer CK,Leitao CB,Pinto LC, et al. Clinical and laboratory profile of patients with type 2 diabetes with low glomerular filtration rate and normoalbuminuria[J]. Diabetes Care, 2007, 30(8): 1998-2000.
[15]
Bhalla V,Zhao B,Azar KM, et al. Racial/ethnic differences in the prevalence of proteinuric and nonproteinuric diabetic kidney disease[J]. Diabetes Care, 2013, 36(5): 1215-1221.
[59]
Nielsen SE,Reinhard H,Zdunek D, et al. Tubular markers are associated with decline in kidney function in proteinuric type 2 diabetic patients[J]. Diabetes Res Clin Pract, 2012, 97(1): 71-76.
[60]
Dwyer JP,Lewis JB. Nonproteinuric diabetic nephropathy: when diabetics don't read the textbook[J]. Med Clin North Am, 2013, 97(1): 53-58.
[16]
Rigalleau V,Lasseur C,Raffaitin C, et al. Normoalbuminuric renal-insufficient diabetic patients: a lower-risk group[J]. Diabetes Care, 2007, 30(8): 2034-2039.
[17]
Retnakaran R,Cull CA,Thorne KI, et al. Risk factors for renal dysfunction in type 2 diabetes: UK Prospective Diabetes Study 74[J]. Diabetes, 2006, 55(6): 1832-1839.
[18]
Yokoyama H,Sone H,Oishi M, et al. Prevalence of albuminuria and renal insufficiency and associated clinical factors in type 2 diabetes: the Japan Diabetes Clinical Data Management study (JDDM15)[J]. Nephrol Dial Transplant, 2009, 24(4): 1212-1219.
[19]
Thomas MC,Macisaac RJ,Jerums G, et al. Nonalbuminuric renal impairment in type 2 diabetic patients and in the general population (national evaluation of the frequency of renal impairment cO-existing with NIDDM [NEFRON]11)[J]. Diabetes Care, 2009, 32(8): 1497-1502.
[1] 何金梅, 尹立雪, 谭静, 张文军, 王锐, 任梅, 廖明娇. 超声心肌做功技术对2型糖尿病患者潜在左心室心肌收缩功能损伤的评价[J]. 中华医学超声杂志(电子版), 2023, 20(10): 1029-1035.
[2] 王珏, 陈赛君, 贲志飞, 詹锦勇, 徐开颖. 剪切波弹性成像联合极速脉搏波技术评估颈动脉弹性对糖尿病性视网膜病变的预测价值[J]. 中华医学超声杂志(电子版), 2023, 20(06): 636-641.
[3] 王洁, 丁泊文, 尹健. 糖尿病性乳腺病52例临床分析[J]. 中华乳腺病杂志(电子版), 2023, 17(05): 285-289.
[4] 陈絮, 詹玉茹, 王纯华. 孕妇ABO血型联合甲状腺功能检测对预测妊娠期糖尿病的临床价值[J]. 中华妇幼临床医学杂志(电子版), 2023, 19(05): 604-610.
[5] 张健, 刘小龙, 查天建, 姚俊杰, 王傑. 富含血小板血浆联合异种脱细胞真皮基质修复糖尿病足缺血性创面的临床效果[J]. 中华损伤与修复杂志(电子版), 2023, 18(06): 503-506.
[6] 赵雅玫, 谢斌, 陈艳, 吴健. 抗生素骨水泥联合负压封闭引流对糖尿病足溃疡临床疗效的荟萃分析[J]. 中华损伤与修复杂志(电子版), 2023, 18(05): 427-433.
[7] 贾蔓箐, 卞婧, 周业平. 对小剂量胰岛素局部注射促进脂肪干细胞移植成活及改善糖尿病创面愈合临床观察[J]. 中华损伤与修复杂志(电子版), 2023, 18(04): 312-316.
[8] 李琛, 张惟佳, 潘亚萍. 牙周炎与系统性疾病之间关系的应用思考:2022年EFP和WONCA欧洲分部联合研讨会共识报告的解读及启示[J]. 中华口腔医学研究杂志(电子版), 2023, 17(05): 322-327.
[9] 叶弘, 吕婧喆, 钟良军. 白藜芦醇治疗牙周炎和糖尿病的新进展[J]. 中华口腔医学研究杂志(电子版), 2023, 17(05): 376-380.
[10] 中国康复医学会器官移植康复专业委员会. 成人实体器官移植后糖尿病管理专家共识[J]. 中华移植杂志(电子版), 2023, 17(04): 205-220.
[11] 周川鹏, 杨浩, 魏微阳, 王奇, 黄亚强. 微创与标准通道经皮肾镜治疗肾结石合并肾功能不全的对比研究[J]. 中华腔镜泌尿外科杂志(电子版), 2023, 17(05): 470-475.
[12] 黄岩, 刘晓巍, 杨春玲, 兰烨. 急性胰腺炎合并糖尿病患者的临床特征及血糖代谢与病情严重度的相关性[J]. 中华消化病与影像杂志(电子版), 2023, 13(06): 439-442.
[13] 张政赢, 鞠阳, 刘晓宁. 二甲双胍对2型糖尿病患者大肠腺瘤术后复发的影响[J]. 中华消化病与影像杂志(电子版), 2023, 13(06): 485-488.
[14] 薛念余, 张盛敏, 吴凌恒, 沙蕾, 童揽月, 沈崔琴, 李朝军, 杜联芳. 研究血清胆红素对2型糖尿病患者心脏结构发生改变前心肌功能的影响[J]. 中华临床医师杂志(电子版), 2023, 17(9): 1004-1009.
[15] 谢国晓, 赵凌霞, 薛雪花. 慢性病管理模式在糖尿病社区管理中的应用[J]. 中华临床医师杂志(电子版), 2023, 17(05): 587-590.
阅读次数
全文


摘要