肾脏疾病的诊治进展与临证经验

1. 肾脏疾病的诊治进展与临证经验 China-Japan Friendship Hospital, Beijing, China Li Ping

2. 肾脏疾病的新分类 急性肾脏损伤（Acute Kidney Injuries, AKI） 慢性肾脏病（Chronic Kidney Disease, CKD）

3. AKI的诊断标准 2005年9月阿姆斯特丹AKI的国际研讨会 ◆ 肾功能在48小时内突然降低 • 至少两次Scr升高绝对值>0.3mg/dl（26.5umol/L） • Scr较前升高50% ◆ 持续6小时以上尿量<0.5ml/kg/h 符合下列条件之一： 单独应用尿量的改变作为诊断标准时，需要除外尿路梗阻或其他可导致尿量减少的原因。 AKIN Organizing Committee 2005

4. AKI的RIFLE分级 反映预后

5. High Sensitivity Increased creatinine x0.5 or  0.3mg/dl UO <0 .5ml/kg/h x 6 hr I UO < 0.5ml/kg/h x 12 hr Increased creatinine x2 II Increase creatinine x3 or creatinine 4mg/dl UO <0.3ml/kg/h x 24 hr or Anuria x 12 hrs III High Specificity AKI合作研讨会标准 2005年9月阿姆斯特丹AKI的国际研讨会 (Acute rise 0.5 mg/dl)

6. AKI的改良RIFLE分级 反映预后 J Himmelfarb. Kidney International (2007) 71, 971–976.

7. AKI的RIFLE分期与预后 2005年bell等回顾性分析207名CRRT治疗的AKI患者 首次采用RIFLE分期评价AKI的预后 R I F L+E Bell. Nephrol Dial Transplant (2005) 20: 354–360

8. 尿量能否界定CRRT的介入时机 A Randomized Controlled study 28例冠脉搭桥术后AKI患者 Early group尿量<30ml/h 持续3h , 14 cases Late group尿量<20ml/h持续2h, 14 cases Early group 86% Late group 14% Souichi. Hemodialysis International. 2004; 8: 320--325

9. RIFLE分期与CRRT介入时机 13% 25% 27% Chih-Chung Shiao. Critical Care.2009, 13:R171

10. Chronic kidney disease（CKD） Chronic kidney disease (CKD) is a worldwide public health problem with an increasing incidence and prevalence, poor outcomes, and high cost. Outcomes of CKD include not only kidney failure but also complications of decreased kidney function and cardiovascular disease. Levey AS, et al. Ann Intern Med. 2003; 139: 137-147.

11. NKF. Am J Kidney Dis. 2002; 39: S1-246.

12. Kidney damage • Kidney damage is defined as pathologic abnormalities or markers of damage, including abnormalities in blood or urine tests or imaging studies. • Persistent proteinuria is the principal marker of kidney damage. • An albumin– creatinine ratio greater than 30 mg/g in two of three spot urine specimens is usually considered abnormal. Levey AS, et al. Kidney Int. 2005; 67: 2089-2100.

13. NKF. Am J Kidney Dis. 2002; 39: S1-246.

14. GFR • GFR can be estimated from calibrated serum creatinine and estimating equations, such as the Modification of Diet in Renal Disease (MDRD) Study equation or the Cockcroft-Gault formula. • The MDRD formula is recommended by European and American guidelines for estimating GFR，which has not been fully validated in different populations and at different stages of CKD NKF. Am J Kidney Dis. 2002; 39: S1-246.

15. Application of GFR-estimating equations in Chinese patients with CKD • To evaluate whether the MDRD equations could be applied accurately to Chinese patients with CKD, GFR estimated by using MDRD equation 7 (7GFR), the abbreviated MDRD equation (aGFR), and the Cockcroft-Gault equation (cGFR) were compared in patients with different stages of CKD. • Dual plasma sampling of technetium Tc 99m-labeled diethylene triamine pentaacetic acid plasma clearance was used as the reference standard GFR (sGFR) for comparison of 7GFRs, aGFRs, and cGFRs at different stages of CKD. • The study enrolled 261 patients with CKD, including 146 men and 115 women. All patients were older than 18 years . Zuo L, et al. Am J Kidney Dis. 2005; 45(3):463-72.

16. Comparison of Equation-Estimated GFRs With 99mTc-DTPA Plasma Clearance Comparison of 7GFR with sGFR showed that 7GFR correlated significantly with sGFR, but the regression line was significantly different from the identical line Zuo L, et al. Am J Kidney Dis. 2005; 45(3):463-72.

17. Performance of GFR-Estimating Equations: Bias, Precision, and Accuracy The regression line showed that MDRD equation 7 overestimated GFR at low levels and underestimated GFR at near-normal levels Zuo L, et al. Am J Kidney Dis. 2005; 45(3):463-72.

18. Performance of the Abbreviated MDRD Equation in Different Stages of CKD *P < 0.05 comparing estimated GFR with sGFR. †P < 0.001 comparing accuracies of an equation with those in CKD stages 4 to 5. Zuo L, et al. Am J Kidney Dis. 2005; 45(3):463-72.

19. Performance of the C-G Equation in Different Stages of CKD *P < 0.05 comparing estimated GFR with sGFR. †P < 0.001 comparing accuracies of an equation with those in CKD stages 4 to 5. ‡P < 0.001 comparing accuracies of the C-G equation with those of the MDRD equations. Zuo L, et al. Am J Kidney Dis. 2005; 45(3):463-72.

20. MDRD equations based on data from Chinese CKD patients • The MDRD equation 7 to estimate GFR (7GFR, ml/min per 1.73m2) = 170 × Pcr-0.999 × age-0.176 × BUN-0.170 × albumin0.318 × 0.762 ( if female) × 1.211 ( if Chinese) • Abbreviated MDRD equation to estimate GFR (aGFR, ml/min per 1.73m2) = 186 × Pcr-1.154 × age-0.203 × 0.742 ( if female) × 1.233 ( if Chinese) Where Pcr is in mg/dl, BUN is in mg/dl, albumin is in g/dl, and age is in years. Ma et al. J Am Soc Nephrol 2006; 17: 2937

21. Prevalence of chronic kidney disease and decreased kidney function in the adult US population:The prevalence of CKD in the US adult population was 11% Third National Health and Nutrition Examination Survey CKD Prevalence Subjects (million) Total Subjects 19.20 11% StageⅠ(Ccr≥90ml/min) 5.90 3.3% StageⅡ(Ccr：60～89ml/min) 5.30 3.0% 7.60 4.3% StageⅢ(Ccr：30～59ml/min) 0.40 0.2% StageⅣ(Ccr：15～29ml/min) 0.30 0.2% StageⅤ(Ccr＜15ml/min) Coresh J, et al. Am J Kidney Dis. 2003; 41: 1-12.

22. Prevalence of kidney damage in Austrinian adults: AusDiab kidney study 11,247 Australians aged 25 yr or over Proteinumia 1.1% 0.6% Renal Impairment 0.3% 9.7% 0.1% 3.7% 0.8% Hematuria Approximately 16.4% have at least one indicator of kidney damage GFR <60 ml/min/1.73m2 （11.2%） Chadban SJ, et al. J Am Soc Nephrol. 2003;14(7 Suppl 2):S131-8.

23. Prevalence of decreased kidney functionin 15,540 Chinese adults aged 35 to 74 years The overall prevalence of CKD with GFR <60 mL/min/1.73m2 was 2.53%. Chen J, et al. Kidney Int. 2005; 68(6):2837-45

24. Age-standardized and age-specific prevalence of decreased kidney function with GFR <60 mL/min/1.73m2 estimated using the simplified MDRD study equation in Chinese adults aged 35 to 74 years Overall, the age-standardized prevalences of GFR 60 to 89, 30 to 59, and <30 mL/min/1.73m2 were 39.4%, 2.4%, and 0.14%, respectively. Chen J, et al. Kidney Int. 2005; 68(6):2837-45.

25. Community-based screening for chronic kidney disease among population older than 40 years in Beijing, China • Subjects: 2353 residents older than 40 years. • Results: Approximately 11.3% of subjects had at least one indicator of kidney damage. (1).Albuminuria(albumin/creatinine≥30mg/g), 6.2%; (2).GFR<60ml/min/1.73m2, 5.2%; (3).Hematuria, 0.8%; (4).Non-infective pyuria, 0.09%. Zhang L, et al. Nephrol Dial Transplant. 2007; 22: 1093

26. Analysis based on 13,519 renal biopsies in China Cases of renal biopsies performed each year Li LS, Liu ZH. Kidney Int. 2004; 66(3): 920-3.

27. The changing frequency of primary and secondary glomerulonephritis from 1979 to 1999 *P < 0.01; **P < 0.001, compared with 1985. Li LS, Liu ZH. Kidney Int. 2004; 66(3): 920-3.

28. Classification of renal diseases based on 13,519 renal biopsies Li LS, Liu ZH. Kidney Int. 2004; 66(3): 920-3.

29. Prevalance of primary glomerular diseases Li LS, Liu ZH. Kidney Int. 2004; 66(3): 920-3.

30. Glomerulonephritis in systemic diseases Li LS, Liu ZH. Kidney Int. 2004; 66(3): 920-3.

31. Glomerular lesions in metabolic diseases Li LS, Liu ZH. Kidney Int. 2004; 66(3): 920-3.

32. Characteristics and changing tendency of renal disease Liu G, et al. J Clin Intern Med. 2004; 21: 834-838

33. The prevalence of ESRD • The worldwide rise in the number of patients with CKD is reflected in the increasing number of people with end-stage renal disease (ESRD) treated by renal replacement therapy—dialysis or transplantation. • Two factors related to the prevalence of ESRD are important. The first is the ageing of the population; The second factor is the global epidemic of type 2 diabetes mellitus. Lysaght MJ. J Am Soc Nephrol. 2002; 13: 37. United States Renal Data System. Am J Kidney Dis. 2003; 42: S37. King H, et al. Diabetes Care. 1998; 21: 1414.

34. Histology of Chinese chronic renal failure (Scr>3mg/dl, N = 607) Li LS, Liu ZH. Kidney Int. 2004; 66(3): 920-3.

35. Chinese maintenance dialysis • According to the registration of dialysis and transplantation in China in 1999, 41775 patients underwent maintenance dialysis; among them, 89.5% was hemodialysis (HD) and 10.5% was peritoneal dialysis (PD). • The first cause of CRF in HD patients was glomerulonephritis (50%), and then diabetic nephropathy (13.5%), hypertensive nephrosclerosis (8.9%). Dialysis and Transplantation Registration Group. Chin J Nephrol. 2001; 17: 77-78.

36. Comparisons of incidence and prevalence of ESRD in developed countries and China These data showed that the annual incidence rate of dialysis in Shanghai, China was coincident with the annual average incidence of ESRD in Europe. However, prevalence of dialysis has marked difference between Europe and Shanghai. The financial problem may be the most important cause of the difference formation. Meguid El, et al. Lancet. 2005; 365: 331-340. Shanghai dialysis and transplantation registration group. Chin J Nephrol. 2001; 17: 83-85.

37. 1658 childhood with CRF in China • The criterion of CRF was creatinine clearance (Ccr) < 50 ml/min/1.73 m2. The mean serum creatinine were 594.7μmol/L. • The average annual cases accounted for 1.31% of the hospitalized cases with urologic-kidney diseases. • The male to female ratio was 1.49:1. • The mean age at the disease onset was 8.18 years. • The mean duration of pre-diagnosis of CRF was 2.53 years. • The main primary renal diseases causing CRF were chronic glomerulonephritis and nephrotic syndrome (52.7%). • One-fourth of all cases had congenital and hereditary renal diseases, and the majority was renal hypoplasia and dysplasia. Yang JY, et al. Zhonghua Er Ke Za Zhi. 2004; 42: 724-730.

38. The major outcomes of CKD • The major outcomes of CKD include progression to kidney failure, complications of decreased kidney function, and CVD. • Data from the NHANES III show the approximately 11% of the U.S. adult population have CKD. The prevalence of early stages of CKD (stages 1 to 4; 10.8%) is more than 100 times greater than the prevalence of kidney failure (stage 5; 0.1%). Coresh J, et al. Am J Kidney Dis. 2003; 41: 1-12.

39. ARF in CKD (A/C) is an important complication of CKD • 104 patients of A/C • accounted for 35.5% of ARF cases with renal biopsy during the same period • drug-induced acute renal interstitial or tubulointerstitial disease, pre-renal ARF and flare-up of lupus nephritis were the most common causes of ARF in A/C patients. • occurred more commonly in older patients Zhang L, et al. Clin Nephrol. 2005; 63: 346-350.

40. CVD is the most important cause of death among Chinese dialysis patients • 2529 cases with dialysis were dead in China in 1999. Heart failure and cerebrovascular accident accounted for 32% and 19%, respectively. • Besides, 16% patients died of dialysis interruption automatically, which might be related to the financial problem. • In another report, CVD is the single most important cause of death among dialysis patients, accounting for 51% of overall mortality. Dialysis and Transplantation Registration Group. Chin J Nephrol. 2001; 17: 77-78.

41. CVD in 1239 Chinese CKD patients The most prevalent pathological form of CVD was left ventricular hypertrophy (LVH), accounting for 58.5% of total patients. Prevalence of CVD (%) 27.7 16.5 5.6 CHF CAD CVA Hou FF, et al. Zhonghua Yi Xue Za Zhi. 2005; 85: 458-463.

42. Epidemiology of cardiovascular risk in Chinese chronic kidney disease patients • C reactive protein • Female and anemia • Calcium phosphate product • Hypoalbuminemia • Diabetes • Age • Hypertension Hou FF, et al. Natl Med J China, 2005; 85: 753-759

43. Prevalence and characteristics of Tuberculosis in 1,498 inpatients with CRF Yuan FH, et al. Ren Fail. 2005; 27: 149-153.

44. Risk factors or risk markers of chronic kidney disease • Hypertension, diabetes, hyperlipidaemia, obesity, and smoking as risk factors or markers in the general population for the development of CKD. • Most notable among the modifiable progression factors is systemic hypertension. • Proteinuria is a reliable marker of the severity of CKD and a powerful and independent predictor of its progression. • Non-modifiable factors include genetics, race, age, and sex. Klag MJ, et al. JAMA. 1997; 277: 1293–1298. Klahr S, et al. N Engl J Med. 1994; 330: 877–884. Jafar TH, et al. Ann Intern Med. 2003; 139: 244–252.

45. IgAN is the most common CKD in China, genetic factors contributing to its pathogenesis • Li YJ, et al. Family-based association study showing that immunoglobulin A nephropathy is associated with the polymorphisms 2093C and 2180T in the 3' untranslated region of the Megsin gene. J Am Soc Nephrol. 2004; 15: 1739-1743. • Li G, et al. Tandem repeats polymorphism of MUC20 is an independent factor for the progression of immunoglobulin A nephropathy. Am J Nephrol. 2006; 26: 43-49. • Lu JC, et al. Uteroglobin G38A polymorphism is associated with the progression of IgA nephropathy in Chinese patients. Zhonghua Nei Ke Za Zhi. 2004; 43: 37-40. • Chen X, et al. Association of angiotensin-converting enzyme gene insertion/deletion polymorphism with the clinico-pathological manifestations in immunoglobulin A nephropathy patients. Chin Med J (Engl). 1997; 110: 526-529. • Megsin 基因与IgA肾病的发病有关 • MUC20，Uteroglobin，ACE 基因与IgA肾病的进展有关

46. Predictors of an unfavourable outcome in IgAN • impaired renal function, • severe proteinuria, • hypertension, • glomerulosclerosis, • interstitial fibrosis D’Amico G. Am J Kidney Dis. 2000; 36: 227–237.

47. Risk factors predicting renal survival of IgAN in 317 Chinese patients P-value Characteristics Scr > 115 umol/L UP > 1.0g/24h Glomerulosclerosis > 2 Crescent formation Interstitial injury > 2 Yang NS, et al. Chin J Intern Med. 2005; l44: 597-600.

48. Multivarite analysis of influercing factors for hypertension in 540 patients with IgAN The prevalence of hypertension in IgAN was 39.6% (214/540) at the time of renal biopsy. Zhuang Y, Chen X, et al. Chin J Intern Med. 2000; 39: 371-375.

49. Characteristics of tubulointerstitial lesions (TIL) in 609 patients with IgAN • Degree and percent of TIL: • mild TIL 47.1%, • moderate TIL 21.7%, • severe TIL 16.6%, • Non-TIL 14.6%. • Related factors with severity of TIL : • hypertension, • the level of proteinuria, • the scores of vascular lesion, • total glomerular lesion, • hypercellularity, • glomerulosclerosis Zhang Y, Chen X, et al. Chin J Intern Med. 2001; 40: 613-617.

50. Prevention of CKD • Primary prevention of CKD will rely on controlling the obesity and associated type 2 diabetes as well as hypertension. • such as weight reduction, exercise, and dietary manipulations. • Secondary prevention of progression of CKD needs pharmacological approaches. Molich M, et al. J Am Soc Nephrol. 2003; 14: S103–107. Appel LJ. J Am Soc Nephrol. 2003; 14: S99–102. Moser M. J Clin Hypertens. 2004; 6: S4–13.