Predicting the outcome of chronic kidney disease by the estimated nephron number: The rationale and design of PRONEP, a prospective, multicenter, observational cohort study

BMC Nephrology

Akira Shimatsu^1,10  Takashi Kenmochi^1,12  Hiroshi Kitamura^1,12  Motonobu Nishimura^1,12  Takehiko Kawaguchi^1,12  Tsuyoshi Yamamura⁴  Ritsuko Katafuchi²  Takaaki Yaomura¹  Osamu Sasaki⁹  Kensei Yahata^1,10  Masaru Nakayama⁵  Mitsuhiro Yoshimura⁷  Yutaka Ando^1,11  Takahito Ito⁶  Ryo Nakajima^1,12  Hiroyuki Fujikawa^1,12  Hiroo Ikehira^1,12  Takashi Nakazato³  Toshiyuki Imasawa⁸ 

[1] National Hospital Organization Nagoya Medical Center, Nagoya, Japan;National Hospital Organization Fukuoka-Higashi Medical Center, Fukuoka, Japan;National Hospital Organization Chiba Medical Center, Chiba, Japan;National Hospital Organization Hokkaido Medical Center, Hokkaido, Japan;National Hospital Organization Kyusyu Medical Center, Fukuoka, Japan;National Hospital Organization Osaka Medical Center, Osaka, Japan;National Hospital Organization Kanazawa Medical Center, Kanazawa, Japan;Department of Nephrology, National Hospital Organization Chiba-East Hospital, 675, Nitona-cho, Chuoh-ku, Ciba-city Chiba 460-8712, Japan;National Hospital Organization Nagasaki Medical Center, Nagasaki, Japan;National Hospital Organization Kyoto Medical Center, Kyoto, Japan;National Hospital Organization Osaka-Minami Medical Center, Osaka, Japan;National Hospital Organization Chiba-East Hospital, Chiba, Japan

关键词: Cortex volume;    Glomerular density;    Kidney biopsy;    Observational cohort study;    Multicenter;    A prospective;    Birth weight;    Nephron number;    Chronic kidney disease;   

Others  :  1083202
DOI  :  10.1186/1471-2369-13-11

 received in 2012-01-31, accepted in 2012-03-10,  发布年份 2012

【 摘 要 】

Background

The nephron number is thought to be associated with the outcome of chronic kidney disease (CKD). If the nephron number can be estimated in the clinical setting, it could become a strong tool to predict renal outcome. This study was designed to estimate the nephron number in CKD patients and to establish a method to predict the outcome by using the estimated nephron number.

Methods/Design

The hypothesis of this study is that the estimated nephron number can predict the outcome of a CKD patient. This will be a multicenter, prospective (minimum 3 and maximum 5 years follow-up) study. The subjects will comprise CKD patients aged over 14 years who have undergone a kidney biopsy. From January 2011 to March 2013, we will recruit 600 CKD patients from 10 hospitals belonging to the National Hospital Organization of Japan. The primary parameter for assessment is the composite of total mortality, renal death, cerebro-cardiovascular events, and a 50% reduction in the eGFR. The secondary parameter is the rate of eGFR decline per year. The nephron number will be estimated by the glomerular density in biopsy specimens and the renal cortex volume. This study includes one sub-cohort study to establish the equation to calculate the renal cortex volume. Enrollment will be performed at the time of the kidney biopsy, and the data will consist of a medical interview, ultrasound for measurement of the kidney size, blood or urine test, and the pathological findings of the kidney biopsy. Patients will continue to have medical consultations and receive examinations and/or treatment as usual. The data from the patients will be collected once a year after the kidney biopsy until March 2016. All data using this study are easily obtained in routine clinical practice.

Discussion

This study includes the first trials to estimate the renal cortex volume and nephron number in the general clinical setting. Furthermore, this is the first prospective study to examine whether the nephron number predicts the outcome of CKD patients. The results from this study should provide powerful new tools for nephrologists in routine clinical practice.

Trial registration

UMIN-Clinical Trial Registration, UMIN000004784.

【 授权许可】

   
2012 Imasawa et al; licensee BioMed Central Ltd.

【 图 表 】

Figure 1.

Figure 2.

Figure 3.

Figure 4.

Figure 5.

Figure 6.

【 参考文献 】

• [1]Mann JF, Gerstein HC, Pogue J, Bosch J, Yusuf S: Renal insufficiency as a predictor of cardiovascular outcomes and the impact of ramipril: the HOPE randomized trial. Ann Intern Med 2001, 134(8):629-636.
• [2]Go AS, Chertow GM, Fan D, McCulloch CE, Hsu CY: Chronic kidney disease and the risks of death, cardiovascular events, and hospitalization. N Engl J Med 2004, 351(13):1296-1305.
• [3]Nakai S, Suzuki K, Masakane I, Wada A, Itami N, Ogata S, Kimata N, Shigematsu T, Shinoda T, Syouji T, Taniguchi M, Tsuchida K, Nakamoto H, Nishi S, Nishi H, Hashimoto S, Hasegawa T, Hanafusa N, Hamano T, Fujii N, Marubayashi S, Morita O, Yamagata K, Wakai K, Watanabe Y, Iseki K, Tsubakihara Y: Overview of regular dialysis treatment in Japan (as of 31 December 2008). Ther Apher Dial 2010, 14(6):505-540.
• [4]Levey AS, Eckardt KU, Tsukamoto Y, Levin A, Coresh J, Rossert J, De Zeeuw D, Hostetter TH, Lameire N, Eknoyan G: Definition and classification of chronic kidney disease: a position statement from Kidney Disease: Improving Global Outcomes (KDIGO). Kidney Int 2005, 67(6):2089-2100.
• [5]Barker DJ, Osmond C, Golding J, Kuh D, Wadsworth ME: Growth in utero, blood pressure in childhood and adult life, and mortality from cardiovascular disease. BMJ 1989, 298(6673):564-567.
• [6]Hoy WE, Rees M, Kile E, Mathews JD, Wang Z: A new dimension to the Barker hypothesis: low birthweight and susceptibility to renal disease. Kidney Int 1999, 56(3):1072-1077.
• [7]Lackland DT, Bendall HE, Osmond C, Egan BM, Barker DJ: Low birth weights contribute to high rates of early-onset chronic renal failure in the Southeastern United States. Arch Intern Med 2000, 160(10):1472-1476.
• [8]Vikse BE, Irgens LM, Leivestad T, Hallan S, Iversen BM: Low birth weight increases risk for end-stage renal disease. J Am Soc Nephrol 2008, 19(1):151-157.
• [9]White SL, Perkovic V, Cass A, Chang CL, Poulter NR, Spector T, Haysom L, Craig JC, Salmi IA, Chadban SJ, Huxley RR: Is low birth weight an antecedent of CKD in later life? A systematic review of observational studies. Am J Kidney Dis 2009, 54(2):248-261.
• [10]Hodgin JB, Rasoulpour M, Markowitz GS, D'Agati VD: Very low birth weight is a risk factor for secondary focal segmental glomerulosclerosis. Clin J Am Soc Nephrol 2009, 4(1):71-76.
• [11]Mañalich R, Reyes L, Herrera M, Melendi C, Fundora I: Relationship between weight at birth and the number and size of renal glomeruli in humans: a histomorphometric study. Kidney Int 2000, 58(2):770-773.
• [12]Hughson M, Farris AB: Douglas-Denton R, Hoy WE, Bertram JF: Glomerular number and size in autopsy kidneys: the relationship to birth weight. Kidney Int 2003, 63(6):2113-2122.
• [13]Luyckx VA, Brenner BM: Low birth weight, nephron number, and kidney disease. Kidney Int (Suppl) 2005, 97:S68-S77.
• [14]Brenner BM, Lawler EV, Mackenzie HS: The hyperfiltration theory: a paradigm shift in nephrology. Kidney Int 1996, 49(6):1774-1777.
• [15]Hoy WE, Hughson MD, Bertram JF, Douglas-Denton R, Amann K: Nephron number, hypertension, renal disease, and renal failure. J Am Soc Nephrol 2005, 16(9):2557-2564.
• [16]Basgen JM, Steffes MW, Stillman AE, Mauer SM: Estimating glomerular number in situ using magnetic resonance imaging and biopsy. Kidney Int 1994, 45(6):1668-1672.
• [17]Fulladosa X, Moreso F, Narváez JA, Grinyó JM, Serón D: Estimation of total glomerular number in stable renal transplants. J Am Soc Nephrol 2003, 14(10):2662-2668.
• [18]National Kidney Foundation: K/DOQI clinical practice guidelines for chronic kidney disease: evaluation, classification, and stratification. Am J Kidney Dis 2002, 2(Suppl 1):S1-266.
• [19]Matsuo S, Imai E, Horio M, Yasuda Y, Tomita K, Nitta K, Yamagata K, Tomino Y, Yokoyama H: Hishida A; Collaborators developing the Japanese equation for estimated GFR: Revised equations for estimated GFR from serum creatinine in Japan. Am J Kidney Dis 2009, 53(6):982-992.
• [20]Nakayama M, Sato T, Sato H, Yamaguchi Y, Obara K, Kurihara I, Sato K, Hotta O, Seino J, Miyata M, Takeuchi K, Nakayama K, Matsushima M, Otaka T, Kinoshita Y, Taguma Y, Ito S: Different clinical outcomes for cardiovascular events and mortality in chronic kidney disease according to underlying renal disease: the Gonryo study. Clin Exp Nephrol 2010, 14(4):333-339.
• [21]Nakayama M, Sato T, Miyazaki M, Matsushima M, Sato H, Taguma Y, Ito S: Increased risk of cardiovascular events and mortality among non-diabetic chronic kidney disease patients with hypertensive nephropathy: the Gonryo study. Hypertens Res 2011, 34(10):1106-1110.
• [22]Shein-chung Chow, Hansheng Wang, Jun Shao: Sample Size Calculations in Clinical Research. 2nd edition. New York: Chapman & Hall/CRC; 2007.
• [23]Miller PL, Meyer TW: Effects of tissue preparation on glomerular volume and capillary structure in the rat. Lab Invest 1990, 63(6):862-866.
• [24]Nyengaard JR: Stereologic methods and their application in kidney research. J Am Soc Nephrol 1999, 10(5):1100-1123.
• [25]Hoy WE, Hughson MD, Singh GR, Douglas-Denton R, Bertram JF: Reduced nephron number and glomerulomegaly in Australian Aborigines: a group at high risk for renal disease and hypertension. Kidney Int 2006, 70(1):104-110.
• [26]Keller G, Zimmer G, Mall G, Ritz E, Amann K: Nephron number in patients with primary hypertension. N Engl J Med 2003, 348(2):101-118.
• [27]Brenner BM, Meyer TW, Hostetter TH: Dietary protein intake and the progressive nature of kidney disease: the role of hemodynamically mediated glomerular injury in the pathogenesis of progressive glomerular sclerosis in aging, renal ablation, and intrinsic renal disease. N Engl J Med 1982, 307(11):652-659.
• [28]Tsuboi N, Kawamura T, Koike K, Okonogi H, Hirano K, Hamaguchi A, Miyazaki Y, Ogura M, Joh K, Utsunomiya Y, Hosoya T: Glomerular density in renal biopsy specimens predicts the long-term prognosis of IgA nephropathy. Clin J Am Soc Nephrol 2010, 5(1):39-44.
• [29]Asselbergs FW, Diercks GF, Hillege HL, van Boven AJ, Janssen WM, Voors AA, de Zeeuw D, de Jong PE, van Veldhuisen DJ, van Gilst WH: Prevention of Renal and Vascular Endstage Disease Intervention Trial (PREVEND IT) Investigators: Effects of fosinopril and pravastatin on cardiovascular events in subjects with microalbuminuria. Circulation 2004, 110(18):2809-2816.
• [30]de Zeeuw D, Remuzzi G, Parving HH, Keane WF, Zhang Z, Shahinfar S, Snapinn S, Cooper ME, Mitch WE, Brenner BM: Albuminuria, a therapeutic target for cardiovascular protection in type 2 diabetic patients with nephropathy. Circulation 2004, 110(8):921-927.
• [31]Olsen MH, Wachtell K, Ibsen H, Lindholm LH, Dahlöf B, Devereux RB, Kjeldsen SE, Oikarinen L: Okin PM; LIFE Study Investigators: Reductions in albuminuria and in electrocardiographic left ventricular hypertrophy independently improve prognosis in hypertension: the LIFE study. J Hypertens 2006, 24(4):775-781.