今日の臨床サポート

蛋白尿

著者: 今井圓裕 中山寺いまいクリニック

監修: 今井圓裕 中山寺いまいクリニック

著者校正/監修レビュー済:2021/09/15
患者向け説明資料
薬剤監修について:
オーダー内の薬剤用量は日本医科大学付属病院 薬剤部 部長 伊勢雄也 以下、林太祐、渡邉裕次、井ノ口岳洋、梅田将光による疑義照会のプロセスを実施、疑義照会の対象については著者の方による再確認を実施しております。
※薬剤中分類、用法、同効薬、診療報酬は、エルゼビアが独自に作成した薬剤情報であり、
著者により作成された情報ではありません。
尚、用法は添付文書より、同効薬は、薬剤師監修のもとで作成しております。
※薬剤情報の(適外/適内/⽤量内/⽤量外/㊜)等の表記は、エルゼビアジャパン編集部によって記載日時にレセプトチェックソフトなどで確認し作成しております。ただし、これらの記載は、実際の保険適用の査定において保険適用及び保険適用外と判断されることを保証するものではありません。また、検査薬、輸液、血液製剤、全身麻酔薬、抗癌剤等の薬剤は保険適用の記載の一部を割愛させていただいています。
(詳細はこちらを参照)
著者のCOI(Conflicts of Interest)開示:
今井圓裕 : 講演料(第一三共,ベーリンガーインゲルハイム,日本イーライリリー,バイエル,田辺三菱),研究費・助成金など(田辺三菱,キッセイ,大日本住友,アストラゼネカ)[2021年]
監修:今井圓裕 : 講演料(第一三共,ベーリンガーインゲルハイム,日本イーライリリー,バイエル,田辺三菱),研究費・助成金など(田辺三菱,キッセイ,大日本住友,アストラゼネカ)[2021年]

改訂のポイント:
  1. 定期レビューを行った(変更なし)。 

病態・疫学・診察

疫学情報・病態・注意事項  
  1. 尿蛋白は、健診や通常の診療で測定される検査である。
  1. 男性の尿蛋白陽性率は年齢により増加し、20歳代では2%であるが、60歳代では5%、80歳では8%に達する 。一方、女性は60歳代までは約2%であるが、70歳代では3%、80歳代では6%である。
  1. 尿蛋白は、独立した強い末期腎不全の予後規定因子である。
 
PREVEND Study

40,548例の予後を961日追跡し、この間に516名が死亡した。178名はCVD、340名はそれ以外の原因による死亡。CVDのRR 1.29 (95% CI: 1.18-1.40)、非CVD死亡のRR 1.12 (95%CI: 1.04-1.21)

出典

img1:  Urinary albumin excretion predicts cardiovascular and noncardiovascular mortality in general population.
 
 Circulation. 2002 Oct 1;106(14):1777-82.・・・
 
  1. 1g/日以上の蛋白尿は治療の対象となるため、腎生検による精査を行う。
  1. 150mg/日のわずかな蛋白尿(30mg/日のアルブミン尿に相当)であっても、心血管疾患の発症のリスクとなる。
 
  1. 日本人の尿蛋白の頻度
  1. 2001~04年に行われた日本の一般住民の574,024人の定期健康診断の結果から、尿蛋白の有病率を示した。男性の尿蛋白陽性率は年齢により増加し、20歳代では2%であるが、60歳代では5%、80歳では8%に達する。女性は60歳代までは約2%であるが、70歳代では3%、80歳代では6%である[1]
 
日本人の尿蛋白の頻度

日本人の尿蛋白の有病率には男女差があり、加齢によりその有病率は増加する。

出典

img1:  Prevalence of chronic kidney disease in the Japanese general population.
 
 Clin Exp Nephrol. 2009 Dec;13(6):621-30.・・・
 
  1. 蛋白尿の量は末期腎不全の発症率と相関し、独立した強い予後推定因子である。
  1. 沖縄の一般住民106,177人を17年間追跡調査すると、尿蛋白陽性者は、透析導入のオッズ比2.71と有意に高値を示した[2]。また、検尿試験紙の-~4+までで層別化すると、男性で±以上、女性で1+以上がリスクとなった。
 
蛋白尿の程度と末期腎不全発症率

沖縄の一般住民106,177人を17年間追跡調査すると、尿蛋白陽性者は、透析導入のオッズ比2.71と有意に高値を示した。また、検尿試験紙の-~4+までで層別化すると、男性で±以上、女性で1+以上がリスクとなった。

出典

img1:  Proteinuria and the risk of developing end-stage renal disease.
 
 Kidney Int. 2003 Apr;63(4):1468-74. doi:・・・
 
  1. 微量アルブミン尿であっても全死亡、心血管死亡の有意なリスクファクターである。
  1. オランダ人40,856人の平均961日間の追跡調査で、心血管死亡の発症のリスクはアルブミン尿が2倍に増加すると、心血管死亡は1.29倍、非心血管死亡は1.12倍に増加する[3]
 
  1. Chronic Kidney Disease Prognosis Consortium
  1. 一般住民105,872人のコホートでメタ解析を行うと、死亡あるいは心血管死亡のリスクは尿アルブミン量が増加するにつれて指数関数的に増加する。アルブミン/クレアチニン比(ACR)0.6mg/mmolと比較して1.1mg/mmolでは、ハザード比1.20(95%CI:1.15-1.26)、13.4mg/mmolでは、1.63(95%CI:1.50-1.77)、33.9mg/mmolでは、2.22(95%CI:1.97-2.51)と上昇する。心血管死亡リスクも同様に上昇する。半定量の尿試験紙法でも同様の結果が得られている[4]
  1. 100万人のコホートのメタ解析で、対数表示された尿アルブミン量が増加すると末期腎不全のリスクは指数関数的に増加することが示された。尿アルブミン量が5mg/gを対象とすると尿アルブミン量が30、300、3,000と増加すると補正ハザード比は5、13、28と増加する(図<図表>)[5]
  1. 尿アルブミン量の増加は、急性腎障害、進行性腎障害(GFR45mL/分/1.73m2未満で、年間GFR低下率2.55mL/分/1.73m2以上)のリスクとも関連する。赤はACR300以上、緑はACR30-299、青はACR30未満を示す(図<図表>)[5]
 
eGFRの低下は全死亡および心血管死亡のリスクを増加させる

ACR:アルブミン/クレアチニン比
eGFR:推算糸球体濾過量

出典

img1:  Association of estimated glomerular filtration rate and albuminuria with all-cause and cardiovascular mortality in general population cohorts: a collaborative meta-analysis.
 
 Lancet. 2010 Jun 12;375(9731):2073-81. d・・・
 
尿アルブミンの増加は末期腎不全のリスクを増大する

ACR:アルブミン/クレアチニン比

出典

img1:  Lower estimated GFR and higher albuminuria are associated with adverse kidney outcomes. A collaborative meta-analysis of general and high-risk population cohorts.
 
 Kidney Int. 2011 Jul;80(1):93-104. doi: ・・・
 
eGFRの低下とアルブミン尿の増加は腎アウトカムの悪化と関連する

a、b:eGFRの低下は末期腎不全のリスクを上昇させる。
c、d:eGFRの低下は急性腎障害のリスクを増加する。
e、f:eGFRの低下は進行性腎障害のリスクを増加する。
アルブミン尿の増加は各リスクを増大する。
 
eGFR:推算糸球体濾過量

出典

img1:  Lower estimated GFR and higher albuminuria are associated with adverse kidney outcomes. A collaborative meta-analysis of general and high-risk population cohorts.
 
 Kidney Int. 2011 Jul;80(1):93-104. doi: ・・・
 
  1. 蛋白尿の改善と予後
  1. オリジナル論文は2001年のLancet(357:1601-08)であるが、尿蛋白を有する患者をメタ解析して得られた結果を図にして示したものである。11の試験に参加した2,387人をメタ解析した結果、短期間の尿蛋白の減少は予後の改善と関係している。また、尿蛋白が増加した患者で予後が改善したものはいなかった。
 
メタ解析:尿蛋白の減少と予後の改善は一致する

尿蛋白が減少すると予後が改善する。
尿蛋白が増加すると予後は悪化する。
尿蛋白が減少して予後が悪化することは少なく、尿蛋白が減少しないのに予後が悪化することはない。

出典

img1:  Dual renin-angiotensin system blockade for nephroprotection: still under scrutiny.
 
 Nephron. 2015;129(1):39-41. doi: 10.1159・・・
問診・診察のポイント  
問診:
  1. これまでの健診における検尿の結果

今なら12か月分の料金で14ヶ月利用できます(個人契約、期間限定キャンペーン)

11月30日(火)までにお申込みいただくと、
通常12ヵ月の使用期間が2ヶ月延長となり、14ヵ月ご利用いただけるようになります。

詳しくはクリック
本サイトの知的財産権は全てエルゼビアまたはコンテンツのライセンサーに帰属します。私的利用及び別途規定されている場合を除き、本サイトの利用はいかなる許諾を与えるものでもありません。 本サイト、そのコンテンツ、製品およびサービスのご利用は、お客様ご自身の責任において行ってください。本サイトの利用に基づくいかなる損害についても、エルゼビアは一切の責任及び賠償義務を負いません。 また、本サイトの利用を以て、本サイト利用者は、本サイトの利用に基づき第三者に生じるいかなる損害についても、エルゼビアを免責することに合意したことになります。  本サイトを利用される医学・医療提供者は、独自の臨床的判断を行使するべきです。本サイト利用者の判断においてリスクを正当なものとして受け入れる用意がない限り、コンテンツにおいて提案されている検査または処置がなされるべきではありません。 医学の急速な進歩に鑑み、エルゼビアは、本サイト利用者が診断方法および投与量について、独自に検証を行うことを推奨いたします。

文献 

著者: Enyu Imai, Masaru Horio, Tsuyoshi Watanabe, Kunitoshi Iseki, Kunihiro Yamagata, Shigeko Hara, Nobuyuki Ura, Yutaka Kiyohara, Toshiki Moriyama, Yasuhiro Ando, Shoichi Fujimoto, Tsuneo Konta, Hitoshi Yokoyama, Hirofumi Makino, Akira Hishida, Seiichi Matsuo
雑誌名: Clin Exp Nephrol. 2009 Dec;13(6):621-30. doi: 10.1007/s10157-009-0199-x. Epub 2009 Jun 11.
Abstract/Text BACKGROUND: We previously estimated the prevalence of chronic kidney disease (CKD) stages 3-5 at 19.1 million based on data from the Japanese annual health check program for 2000-2004 using the Modification of Diet in Renal Disease (MDRD) equation multiplied by the coefficient 0.881 for the Japanese population. However, this equation underestimates the GFR, particularly for glomerular filtration rates (GFRs) of over 60 ml/min/1.73 m(2). We did not classify the participants as CKD stages 1 and 2 because we did not obtain proteinuria data for all of the participants. We re-estimated the prevalence of CKD by measuring proteinuria using a dipstick test and by calculating the GFR using a new equation that estimates GFR based on data from the Japanese annual health check program in 2005.
METHODS: Data were obtained for 574,024 (male 240,594, female 333,430) participants over 20 years old taken from the general adult population, who were from 11 different prefectures in Japan (Hokkaido, Yamagata, Fukushima, Tochigi, Ibaraki, Tokyo, Kanazawa, Osaka, Fukuoka, Miyazaki and Okinawa) and took part in the annual health check program in 2005. The glomerular filtration rate (GFR) of each participant was computed from the serum creatinine value using a new equation: GFR (ml/min/1.73 m(2)) = 194 x Age(-0.287) x S-Cr(-1.094) (if female x 0.739). The CKD population nationwide was calculated using census data from 2005. We also recalculated the prevalence of CKD in Japan assuming that the age composition of the population was same as that in the USA.
RESULTS: The prevalence of CKD stages 1, 2, 3, and 4 + 5 were 0.6, 1.7, 10.4 and 0.2% in the study population, which resulted in predictions of 0.6, 1.7, 10.7 and 0.2 million patients, respectively, nationwide. The prevalence of low GFR was significantly higher in the hypertensive and proteinuric populations than it was in the populations without proteinuria or hypertension. The prevalence rate of CKD in Japan was similar to that in the USA when the Japanese general population was age adjusted to the US 2005 population estimate.
CONCLUSION: About 13% of the Japanese adult population-approximately 13.3 million people-were predicted to have CKD in 2005.

PMID 19513802  Clin Exp Nephrol. 2009 Dec;13(6):621-30. doi: 10.1007/s・・・
著者: Kunitoshi Iseki, Yoshiharu Ikemiya, Chiho Iseki, Shuichi Takishita
雑誌名: Kidney Int. 2003 Apr;63(4):1468-74. doi: 10.1046/j.1523-1755.2003.00868.x.
Abstract/Text BACKGROUND: Dipstick urinalysis for proteinuria and hematuria has been used to screen renal disease, but evidence of the clinical impact of this test on development of end-stage renal disease (ESRD) is lacking.
METHODS: We assessed development of ESRD through 2000 in 106,177 screened patients (50,584 men and 55,593 women), 20 to 98 years old, in Okinawa, Japan, who participated in community-based mass screening between April 1983 and March 1984. We used data from the Okinawa Dialysis Study Registry to identify ESRD patients. Multivariate logistic analyses were performed to calculate adjusted odds ratio and 95% confidence interval (95% CI) for the significance of proteinuria and hematuria on the risk of developing ESRD with confounding variables such as age, gender, blood pressure, and body mass index. A similar analysis was repeated in a subgroup of screened patients in whom serum creatinine data existed.
RESULTS: During 17 years of follow-up, 420 screened persons (246 men and 174 women) entered the ESRD program. We identified a strong, graded relationship between ESRD and dipstick urinalysis positive for proteinuria; adjusted odds ratio (95% CI) was 2.71 (2.51 to 2.92, P < 0.001). Similar trends were observed after adding serum creatinine data. Compared with dipstick-negative proteinuria, adjusted odds ratio (95% CI) of proteinuria (1+) was 1.93 (1.53 to 2.41, P < 0.001) in men and 2.42 (1.91 to 3.06, P < 0.001) in women.
CONCLUSION: Proteinuria was a strong, independent predictor of ESRD in a mass screening setting. Even a slight increase in proteinuria was an independent risk factor for ESRD. Therefore, asymptomatic proteinuria warrants further work-up and intervention.

PMID 12631363  Kidney Int. 2003 Apr;63(4):1468-74. doi: 10.1046/j.1523・・・
著者: Hans L Hillege, Vaclav Fidler, Gilles F H Diercks, Wiek H van Gilst, Dick de Zeeuw, Dirk J van Veldhuisen, Rijk O B Gans, Wilbert M T Janssen, Diederick E Grobbee, Paul E de Jong, Prevention of Renal and Vascular End Stage Disease (PREVEND) Study Group
雑誌名: Circulation. 2002 Oct 1;106(14):1777-82.
Abstract/Text BACKGROUND: For the general population, the clinical relevance of an increased urinary albumin excretion rate is still debated. Therefore, we examined the relationship between urinary albumin excretion and all-cause mortality and mortality caused by cardiovascular (CV) disease and non-CV disease in the general population.
METHODS AND RESULTS: In the period 1997 to 1998, all inhabitants of the city of Groningen, the Netherlands, aged between 28 and 75 years (n=85 421) were sent a postal questionnaire collecting information about risk factors for CV disease and CV morbidity and a vial to collect an early morning urine sample for measurement of urinary albumin concentration (UAC). The vital status of the cohort was subsequently obtained from the municipal register, and the cause of death was obtained from the Central Bureau of Statistics. Of these 85 421 subjects, 40 856 (47.8%) responded, and 40 548 could be included in the analysis. During a median follow-up period of 961 days (maximum 1139 days), 516 deaths with known cause were recorded. We found a positive dose-response relationship between increasing UAC and mortality. A higher UAC increased the risk of both CV and non-CV death after adjustment for other well-recognized CV risk factors, with the increase being significantly higher for CV mortality than for non-CV mortality (P=0.014). A 2-fold increase in UAC was associated with a relative risk of 1.29 for CV mortality (95% CI 1.18 to 1.40) and 1.12 (95% CI 1.04 to 1.21) for non-CV mortality.
CONCLUSIONS: Urinary albumin excretion is a predictor of all-cause mortality in the general population. The excess risk was more attributable to death from CV causes, independent of the effects of other CV risk factors, and the relationship was already apparent at levels of albuminuria currently considered to be normal.

PMID 12356629  Circulation. 2002 Oct 1;106(14):1777-82.
著者: Chronic Kidney Disease Prognosis Consortium, Kunihiro Matsushita, Marije van der Velde, Brad C Astor, Mark Woodward, Andrew S Levey, Paul E de Jong, Josef Coresh, Ron T Gansevoort
雑誌名: Lancet. 2010 Jun 12;375(9731):2073-81. doi: 10.1016/S0140-6736(10)60674-5. Epub 2010 May 17.
Abstract/Text BACKGROUND: Substantial controversy surrounds the use of estimated glomerular filtration rate (eGFR) and albuminuria to define chronic kidney disease and assign its stages. We undertook a meta-analysis to assess the independent and combined associations of eGFR and albuminuria with mortality.
METHODS: In this collaborative meta-analysis of general population cohorts, we pooled standardised data for all-cause and cardiovascular mortality from studies containing at least 1000 participants and baseline information about eGFR and urine albumin concentrations. Cox proportional hazards models were used to estimate hazard ratios (HRs) for all-cause and cardiovascular mortality associated with eGFR and albuminuria, adjusted for potential confounders.
FINDINGS: The analysis included 105,872 participants (730,577 person-years) from 14 studies with urine albumin-to-creatinine ratio (ACR) measurements and 1,128,310 participants (4,732,110 person-years) from seven studies with urine protein dipstick measurements. In studies with ACR measurements, risk of mortality was unrelated to eGFR between 75 mL/min/1.73 m(2) and 105 mL/min/1.73 m(2) and increased at lower eGFRs. Compared with eGFR 95 mL/min/1.73 m(2), adjusted HRs for all-cause mortality were 1.18 (95% CI 1.05-1.32) for eGFR 60 mL/min/1.73 m(2), 1.57 (1.39-1.78) for 45 mL/min/1.73 m(2), and 3.14 (2.39-4.13) for 15 mL/min/1.73 m(2). ACR was associated with risk of mortality linearly on the log-log scale without threshold effects. Compared with ACR 0.6 mg/mmol, adjusted HRs for all-cause mortality were 1.20 (1.15-1.26) for ACR 1.1 mg/mmol, 1.63 (1.50-1.77) for 3.4 mg/mmol, and 2.22 (1.97-2.51) for 33.9 mg/mmol. eGFR and ACR were multiplicatively associated with risk of mortality without evidence of interaction. Similar findings were recorded for cardiovascular mortality and in studies with dipstick measurements.
INTERPRETATION: eGFR less than 60 mL/min/1.73 m(2) and ACR 1.1 mg/mmol (10 mg/g) or more are independent predictors of mortality risk in the general population. This study provides quantitative data for use of both kidney measures for risk assessment and definition and staging of chronic kidney disease.
FUNDING: Kidney Disease: Improving Global Outcomes (KDIGO), US National Kidney Foundation, and Dutch Kidney Foundation.

Copyright 2010 Elsevier Ltd. All rights reserved.
PMID 20483451  Lancet. 2010 Jun 12;375(9731):2073-81. doi: 10.1016/S01・・・
著者: Ron T Gansevoort, Kunihiro Matsushita, Marije van der Velde, Brad C Astor, Mark Woodward, Andrew S Levey, Paul E de Jong, Josef Coresh, Chronic Kidney Disease Prognosis Consortium
雑誌名: Kidney Int. 2011 Jul;80(1):93-104. doi: 10.1038/ki.2010.531. Epub 2011 Feb 2.
Abstract/Text Both a low estimated glomerular filtration rate (eGFR) and albuminuria are known risk factors for end-stage renal disease (ESRD). To determine their joint contribution to ESRD and other kidney outcomes, we performed a meta-analysis of nine general population cohorts with 845,125 participants and an additional eight cohorts with 173,892 patients, the latter selected because of their high risk for chronic kidney disease (CKD). In the general population, the risk for ESRD was unrelated to eGFR at values between 75 and 105 ml/min per 1.73 m(2) but increased exponentially at lower levels. Hazard ratios for eGFRs averaging 60, 45, and 15 were 4, 29, and 454, respectively, compared with an eGFR of 95, after adjustment for albuminuria and cardiovascular risk factors. Log albuminuria was linearly associated with log ESRD risk without thresholds. Adjusted hazard ratios at albumin-to-creatinine ratios of 30, 300, and 1000 mg/g were 5, 13, and 28, respectively, compared with an albumin-to-creatinine ratio of 5. Albuminuria and eGFR were associated with ESRD, without evidence for multiplicative interaction. Similar associations were found for acute kidney injury and progressive CKD. In high-risk cohorts, the findings were generally comparable. Thus, lower eGFR and higher albuminuria are risk factors for ESRD, acute kidney injury and progressive CKD in both general and high-risk populations, independent of each other and of cardiovascular risk factors.

PMID 21289597  Kidney Int. 2011 Jul;80(1):93-104. doi: 10.1038/ki.2010・・・
著者: Shinichi Tanihara, Takehito Hayakawa, Izumi Oki, Yosikazu Nakamura, Kiyomi Sakata, Akira Okayama, Yasuyuki Fujita, Hirotsugu Ueshima, NIPPON DATA Research Group
雑誌名: J Epidemiol. 2005 Jul;15(4):146-53.
Abstract/Text BACKGROUND: Proteinuria has been considered to be a prognostic marker for persons with diabetes mellitus, but only a limited number of studies about the relationship between proteinuria and mortality among general population has been available.
METHODS: The subjects were 10,897 individuals who participated in the National Cardiovascular Survey conducted in 1980 and who were aged 30 years or older living in 300 districts that had been randomly selected throughout Japan. The vital records were confirmed in 1999 and 7,203 subjects (3,180 males and 4,023 females) without a history of hypertension, stroke, heart disease, renal disease, or diabetes mellitus at the start of the study were investigated.
RESULTS: There were 126,825 person-years of follow-up. During the observed period of time, 371 died of cardiovascular causes, including 171 stroke deaths and 74 coronary deaths. The risk of proteinuria for cardiovascular mortality was greater than unity for those with a normal serum creatinine level, after adjusting for age and other cardiovascular disease risk factors.
CONCLUSIONS: When contrasted with other cardiovascular disease risk factors, urinary protein is an independent risk factor for cardiovascular death among the Japanese population.

PMID 16141633  J Epidemiol. 2005 Jul;15(4):146-53.
著者: Robert G Weaver, Matthew T James, Pietro Ravani, Colin G W Weaver, Edmund J Lamb, Marcello Tonelli, Braden J Manns, Robert R Quinn, Min Jun, Brenda R Hemmelgarn
雑誌名: J Am Soc Nephrol. 2020 Mar;31(3):591-601. doi: 10.1681/ASN.2019060605. Epub 2020 Feb 5.
Abstract/Text BACKGROUND: Urine albumin-to-creatinine ratio (ACR) and protein-to-creatinine ratio (PCR) are used to measure urine protein. Recent guidelines endorse ACR use, and equations have been developed incorporating ACR to predict risk of kidney failure. For situations in which PCR only is available, having a method to estimate ACR from PCR as accurately as possible would be useful.
METHODS: We used data from a population-based cohort of 47,714 adults in Alberta, Canada, who had simultaneous assessments of urine ACR and PCR. After log-transforming ACR and PCR, we used cubic splines and quantile regression to estimate the median ACR from a PCR, allowing for modification by specified covariates. On the basis of the cubic splines, we created models using linear splines to develop equations to estimate ACR from PCR. In a subcohort with eGFR<60 ml/min per 1.73 m2, we then used the kidney failure risk equation to compare kidney failure risk using measured ACR as well as estimated ACR that had been derived from PCR.
RESULTS: We found a nonlinear association between log(ACR) and log(PCR), with the implied albumin-to-protein ratio increasing from <30% in normal to mild proteinuria to about 70% in severe proteinuria, and with wider prediction intervals at lower levels. Sex was the most important modifier of the relationship between ACR and PCR, with men generally having a higher albumin-to-protein ratio. Estimates of kidney failure risk were similar using measured ACR and ACR estimated from PCR.
CONCLUSIONS: We developed equations to estimate the median ACR from a PCR, optionally including specified covariates. These equations may prove useful in certain retrospective clinical or research applications where only PCR is available.

Copyright © 2020 by the American Society of Nephrology.
PMID 32024663  J Am Soc Nephrol. 2020 Mar;31(3):591-601. doi: 10.1681/・・・
著者: Hiddo J L Heerspink, Tom Greene, Hocine Tighiouart, Ron T Gansevoort, Josef Coresh, Andrew L Simon, Tak Mao Chan, Fan Fan Hou, Julia B Lewis, Francesco Locatelli, Manuel Praga, Francesco Paolo Schena, Andrew S Levey, Lesley A Inker, Chronic Kidney Disease Epidemiology Collaboration
雑誌名: Lancet Diabetes Endocrinol. 2019 Feb;7(2):128-139. doi: 10.1016/S2213-8587(18)30314-0. Epub 2019 Jan 8.
Abstract/Text BACKGROUND: Change in albuminuria has strong biological plausibility as a surrogate endpoint for progression of chronic kidney disease, but empirical evidence to support its validity is lacking. We aimed to determine the association between treatment effects on early changes in albuminuria and treatment effects on clinical endpoints and surrograte endpoints, to inform the use of albuminuria as a surrogate endpoint in future randomised controlled trials.
METHODS: In this meta-analysis, we searched PubMed for publications in English from Jan 1, 1946, to Dec 15, 2016, using search terms including "chronic kidney disease", "chronic renal insufficiency", "albuminuria", "proteinuria", and "randomized controlled trial"; key inclusion criteria were quantifiable measurements of albuminuria or proteinuria at baseline and within 12 months of follow-up and information on the incidence of end-stage kidney disease. We requested use of individual patient data from the authors of eligible studies. For all studies that the authors agreed to participate and that had sufficient data, we estimated treatment effects on 6-month change in albuminuria and the composite clinical endpoint of treated end-stage kidney disease, estimated glomerular filtration rate of less than 15 mL/min per 1·73 m2, or doubling of serum creatinine. We used a Bayesian mixed-effects meta-regression analysis to relate the treatment effects on albuminuria to those on the clinical endpoint across studies and developed a prediction model for the treatment effect on the clinical endpoint on the basis of the treatment effect on albuminuria.
FINDINGS: We identified 41 eligible treatment comparisons from randomised trials (referred to as studies) that provided sufficient patient-level data on 29 979 participants (21 206 [71%] with diabetes). Over a median follow-up of 3·4 years (IQR 2·3-4·2), 3935 (13%) participants reached the composite clinical endpoint. Across all studies, with a meta-regression slope of 0·89 (95% Bayesian credible interval [BCI] 0·13-1·70), each 30% decrease in geometric mean albuminuria by the treatment relative to the control was associated with an average 27% lower hazard for the clinical endpoint (95% BCI 5-45%; median R2 0·47, 95% BCI 0·02-0·96). The association strengthened after restricting analyses to patients with baseline albuminuria of more than 30 mg/g (ie, 3·4 mg/mmol; R2 0·72, 0·05-0·99]). For future trials, the model predicts that treatments that decrease the geometric mean albuminuria to 0·7 (ie, 30% decrease in albuminuria) relative to the control will provide an average hazard ratio (HR) for the clinical endpoint of 0·68, and 95% of sufficiently large studies would have HRs between 0·47 and 0·95.
INTERPRETATION: Our results support a role for change in albuminuria as a surrogate endpoint for the progression of chronic kidney disease, particularly in patients with high baseline albuminuria; for patients with low baseline levels of albuminuria this association is less certain.
FUNDING: US National Kidney Foundation.

Copyright © 2019 Elsevier Ltd. All rights reserved.
PMID 30635226  Lancet Diabetes Endocrinol. 2019 Feb;7(2):128-139. doi:・・・

ページ上部に戻る

戻る

さらなるご利用にはご登録が必要です。

こちらよりご契約または優待日間無料トライアルお申込みをお願いします。

(※トライアルご登録は1名様につき、一度となります)


ご契約の場合はご招待された方だけのご優待特典があります。

以下の優待コードを入力いただくと、

契約期間が通常12ヵ月のところ、14ヵ月ご利用いただけます。

優待コード: (利用期限:まで)

ご契約はこちらから