今日の臨床サポート

慢性糸球体腎炎

著者: 永澤元規1) 大阪大学医学部附属病院・老年総合内科

著者: 安田 隆2) 吉祥寺あさひ病院

監修: 木村健二郎 地域医療機能推進機構 東京高輪病院

著者校正/監修レビュー済:2022/07/06
患者向け説明資料

概要・推奨   

  1. RA系阻害薬は糖尿病性腎症のみならず非糖尿病性腎疾患においても蛋白尿を減少させ、腎機能障害の進行を抑制する効果が示されている。慢性糸球体腎炎を含む蛋白尿を有する患者にはRA系阻害薬を使用することが勧められる(推奨度1)
  1. 慢性糸球体腎炎で最も多いIgA腎症の治療においては、リスク群に応じて異なっており、ステロイド治療が有用である。日本においては扁桃摘出術+ステロイドパルス療法も多く施行されている(推奨度1)
  1. IgA腎症は若年の発症が多く、妊娠に関する問題があるが、高血圧を認めず、腎機能も保たれていれば妊娠経過は良好であり、長期予後にも影響しない。ただし活動性の半月体形成、尿細管間質障害、ネフローゼ症候群を呈している場合には腎機能が悪化する可能性が高いとされている(推奨度2)
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  1. 閲覧にはご契約が必要となります。閲覧にはご契約が必要となります。閲覧にはご契約が必要となります。閲覧にはご契約が必要となります。閲覧にはご契約が必要となります。閲覧にはご契約が必要となります。閲
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。
※同効薬・小児・妊娠および授乳中の注意事項等は、海外の情報も掲載しており、日本の医療事情に適応しない場合があります。
※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、実際の保険適応の査定において保険適応及び保険適応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応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:
永澤元規 : 特に申告事項無し[2022年]
安田 隆 : 特に申告事項無し[2022年]
監修:木村健二郎 : 未申告[2022年]

改訂のポイント:
  1. 上記ガイドラインに基づき改訂を行った。

病態・疫学・診察

疾患情報(疫学・病態)  
  1. 慢性糸球体腎炎は、蛋白尿血尿が持続的に認められ、経過とともに浮腫、高血圧などの臨床症状や腎機能低下を認めるものをいう。
  1. 慢性糸球体腎炎は、上記の症状、検査所見を呈する症候群的病名であり、原因疾患はさまざまである。
  1. IgA腎症を代表とする一次性(原発性)以外に、全身性エリテマトーデス、紫斑病(IgA血管炎)などの全身性疾患に伴う二次性(続発性)のもの、そして菲薄基底膜症候群などの遺伝性のものがある。
  1. 透析導入の原因疾患としては、糖尿病性腎症に1998年以降、第1位の座を、また2019年には腎硬化症に第2位の座を譲り、診断と管理の改善により順調に減少傾向が続いている。
  1. 慢性糸球体腎炎のなかで、IgA腎症が最も多く、約40%を占めている。
問診、診察のポイント  
  1. 経過を確認する:尿潜血、蛋白尿の出現時期、健診結果、肉眼的血尿の有無、上気道感染との関連の有無などを聴取する。

これより先の閲覧には個人契約のトライアルまたはお申込みが必要です。

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文献 

Vinata B Lokeshwar, Tomonori Habuchi, H Barton Grossman, William M Murphy, Stefan H Hautmann, George P Hemstreet, Aldo V Bono, Robert H Getzenberg, Peter Goebell, Bernd J Schmitz-Dräger, Jack A Schalken, Yves Fradet, Michael Marberger, Edward Messing, Michael J Droller
Bladder tumor markers beyond cytology: International Consensus Panel on bladder tumor markers.
Urology. 2005 Dec;66(6 Suppl 1):35-63. doi: 10.1016/j.urology.2005.08.064.
Abstract/Text This is the first of 2 articles that summarize the findings of the International Consensus Panel on cytology and bladder tumor markers. The objectives of our panel were to reach a consensus on the areas where markers are needed, to define the attributes of an ideal tumor marker, and to identify which marker(s) would be suitable for diagnosis and/or surveillance of bladder cancer. Our panel consisted of urologists and researchers from Europe, Asia, and the United States who reviewed original articles, reviews, and book chapters on individual bladder tumor markers published in the English language mainly using the PubMed search engine. Panel members also met during 3 international meetings to write recommendations regarding bladder tumor markers. The panel found that the most practical use of noninvasive tests is to monitor bladder cancer recurrence, thereby reducing the number of surveillance cystoscopies performed each year. Markers also may be useful in the screening of high-risk individuals for early detection of bladder cancer. However, more prospective studies are needed to strengthen this argument. Case-control and cohort studies show that several markers have a higher sensitivity to detect bladder cancer. However, cytology is the superior marker in terms of specificity, although some markers in limited numbers of studies have shown specificity equivalent to that of cytology. Our panel believes that several bladder tumor markers are more accurate in detecting bladder cancer than prostate-specific antigen (PSA) is in detecting prostate cancer. However, bladder tumor markers are held to a higher standard than PSA. Therefore, use of bladder tumor markers in the management of patients with bladder cancer will require the willingness of both urologists and clinicians to accept them.

PMID 16399415
S Abe
Pregnancy in IgA nephropathy.
Kidney Int. 1991 Dec;40(6):1098-102.
Abstract/Text The impacts of IgA nephropathy and pregnancy on each other were evaluated in 118 women who conceived 168 times between 1970 and 1988. Rates of spontaneous abortion, normal delivery, live birth and perinatal death were 9, 66, 87 and 4%, respectively. Infants born to women with glomerular filtration rates (GFR) lower than 70 ml/min prior to conception had a higher perinatal mortality rate (14% vs. 3%, P less than 0.001). This was also true if pre-pregnancy blood pressures were consistently higher than 140/90 mm Hg (33% vs. 1%, P less than 0.001). These were the figures for the whole 18 year period, but stratification of the data revealed that most adverse results occurred in the 1970's, during which the perinatal death rate was 9%, while it was 0% in the 1980's. Eighty-five women were followed for three years or more. At final follow-up, the rates of decrease in GFR, and increases in blood pressure and proteinuria were 19, 11 and 7%, respectively. In most patients the natural history of IgA nephropathy was similar to that of women who had not experienced pregnancy, but there were five instances where gestation seemed to accelerate functional loss, with rapid development of end-stage or near end-stage renal failure. Most women with IgA nephropathy should anticipate few problems with pregnancy, if they are normotensive and their preconception GFR exceeds 70 ml/min. The gestation in such instances should have little influence on the natural history of their nephropathy.

PMID 1762310
Monica Limardo, Enrico Imbasciati, Pietro Ravani, Maurizio Surian, Diletta Torres, Gina Gregorini, Riccardo Magistroni, Daniela Casellato, Linda Gammaro, Claudio Pozzi, Rene e Gravidanza Collaborative Group of the Italian Society of Nephrology
Pregnancy and progression of IgA nephropathy: results of an Italian multicenter study.
Am J Kidney Dis. 2010 Sep;56(3):506-12. doi: 10.1053/j.ajkd.2010.03.033.
Abstract/Text BACKGROUND: Whether pregnancy impacts on the long-term outcome of immunoglobulin A (IgA) nephropathy is unknown. This study aims to compare the long-term outcome of kidney disease in women with IgA nephropathy and preserved kidney function who did and did not become pregnant.
STUDY DESIGN: Multicenter longitudinal cohort study.
SETTING & PARTICIPANTS: Women of childbearing age with biopsy-proven IgA nephropathy, serum creatinine levelPREDICTORS: Pregnancy, treated as a time-dependent variable; baseline proteinuria; hypertension; and kidney biopsy histologic characteristics.
OUTCOME & MEASURES: Rate of change in estimated creatinine clearance, change in proteinuria, and new-onset hypertension.
RESULTS: 245 patients were enrolled. Of these, 223 women (136 and 87 in the pregnancy and nonpregnancy groups, respectively) had serum creatinine levelsLIMITATIONS: Unrecognized or unmeasured factors associated with the decision of becoming pregnant might have influenced results.
CONCLUSIONS: Pregnancy does not seem to affect the long-term outcome of kidney disease in women with IgA nephropathy and preserved kidney function.

Copyright (c) 2010 National Kidney Foundation, Inc. Published by Elsevier Inc. All rights reserved.
PMID 20599307
Ari Shimizu, Takashi Takei, Takahito Moriyama, Mitsuyo Itabashi, Keiko Uchida, Kosaku Nitta
Effect of kidney disease stage on pregnancy and delivery outcomes among patients with immunoglobulin A nephropathy.
Am J Nephrol. 2010;32(5):456-61. doi: 10.1159/000320730. Epub 2010 Oct 6.
Abstract/Text BACKGROUND: Immunoglobulin A nephropathy (IgAN) has a peak onset that coincides with the reproductive age. Therefore, many young women who are affected become pregnant. The effects and outcome of pregnancy in women with renal diseases remain controversial, and the characteristics and outcome of pregnancy in IgAN patients must be further evaluated.
METHODS: A prospective follow-up study of 29 pregnant women with IgAN was performed by analyzing laboratory data, histology and prognosis. To clarify the influence of renal insufficiency, we compared these patients according to the chronic kidney disease (CKD) stage.
RESULTS: We found that pregnancy and delivery did not produce any significant changes of the renal function in any of the patients at 3 years after delivery, although the proteinuria was elevated at 30 weeks of pregnancy and at 3 months after delivery. Finally, the data of pregnant women with IgAN were compared with those of 45 nonpregnant women who had similar clinical and demographic characteristics.
CONCLUSION: The pregnant patients with IgAN did not exhibit any significant reduction of renal function at 3 years after delivery as compared with the baseline, which is similar to the findings in nonpregnant patients. Furthermore, pregnancy with stage 2 or 3 CKD was not a risk factor for renal dysfunction or delivery.

Copyright © 2010 S. Karger AG, Basel.
PMID 20924168
François Berthoux, Hesham Mohey, Blandine Laurent, Christophe Mariat, Aida Afiani, Lise Thibaudin
Predicting the risk for dialysis or death in IgA nephropathy.
J Am Soc Nephrol. 2011 Apr;22(4):752-61. doi: 10.1681/ASN.2010040355. Epub 2011 Jan 21.
Abstract/Text For the individual patient with primary IgA nephropathy (IgAN), it remains a challenge to predict long-term outcomes for patients receiving standard treatment. We studied a prospective cohort of 332 patients with biopsy-proven IgAN patients followed over an average of 13 years. We calculated an absolute renal risk (ARR) of dialysis or death by counting the number of risk factors present at diagnosis: hypertension, proteinuria ≥1 g/d, and severe pathologic lesions (global optical score, ≥8). Overall, the ARR score allowed significant risk stratification (P < 0.0001). The cumulative incidence of death or dialysis at 10 and 20 years was 2 and 4%, respectively, for ARR=0; 2 and 9% for ARR=1; 7 and 18% for ARR=2; and 29 and 64% for ARR=3, in adequately treated patients. When achieved, control of hypertension and reduction of proteinuria reduced the risk for death or dialysis. In conclusion, the absolute renal risk score, determined at diagnosis, associates with risk for dialysis or death.

Copyright © 2011 by the American Society of Nephrology
PMID 21258035
Heather N Reich, Stéphan Troyanov, James W Scholey, Daniel C Cattran, Toronto Glomerulonephritis Registry
Remission of proteinuria improves prognosis in IgA nephropathy.
J Am Soc Nephrol. 2007 Dec;18(12):3177-83. doi: 10.1681/ASN.2007050526. Epub 2007 Oct 31.
Abstract/Text Proteinuria has been shown to be an adverse prognostic factor in IgA nephropathy. The benefit of achieving a partial remission of proteinuria, however, has not been well described. We studied 542 patients with biopsy-proven primary IgA nephropathy in the Toronto Glomerulonephritis Registry and found that glomerular filtration rate (GFR) declined at -0.38 +/- 0.61 ml/min per 1.73 m2/mo overall, with 30% of subjects reaching end-stage renal disease. Multivariate analysis revealed that proteinuria during follow-up was the most important predictor of the rate of GFR decline. Among the 171 patients with <1 g/d of sustained proteinuria, the rate of decline was 90% slower than the mean rate. The rate of decline increased with the amount of proteinuria, such that those with sustained proteinuria >3 g/d (n = 121) lost renal function 25-fold faster than those with <1 g/d. Patients who presented with > or =3 g/d who achieved a partial remission (<1 g/d) had a similar course to patients who had < or =1 g/d throughout, and fared far better than patients who never achieved remission. These results underscore the relationship between proteinuria and prognosis in IgA nephropathy and establish the importance of remission.

PMID 17978307
D Fouque, P Wang, M Laville, J P Boissel
Low protein diets delay end-stage renal disease in non-diabetic adults with chronic renal failure.
Nephrol Dial Transplant. 2000 Dec;15(12):1986-92.
Abstract/Text BACKGROUND: The objective of this study was to determine the efficacy of low protein diets in delaying the need to start maintenance dialysis based on an analysis of published literature.
METHODS: The search strategy involved a Medline and Embase search from January 1966 through to June 1999, congress abstracts (American Society of Nephrology since 1990, European Dialysis Transplant Association since 1985, International Society of Nephrology since 1987) and direct contacts with investigators. The selection criteria included randomized trials comparing two different levels of protein intake in adult patients suffering from moderate to severe renal failure, followed for at least 1 year. Patients with diabetic nephropathy were excluded. Seven trials were selected from 40 studies since 1975. A total of 1494 patients were analysed: 753 had received reduced protein intake and 741 a higher protein intake. The numbers of 'renal deaths' (defined as the need for starting dialysis, the death of a patient or kidney transplant during the trial) were collected.
RESULTS: 242 renal deaths were recorded, 101 in the low protein diet and 141 in the higher protein diet group, giving an odds ratio of 0.61 with a 95% confidence interval of 0.46 to 0.83 (P=0.006).
CONCLUSION: Reducing protein intake in patients with chronic renal failure reduces the occurrence of renal death by about 40% as compared with larger or unrestricted protein intake. The optimal level of protein intake cannot be confirmed from these studies.

PMID 11096144
G D'Amico, M G Gentile, G Fellin, G Manna, F Cofano
Effect of dietary protein restriction on the progression of renal failure: a prospective randomized trial.
Nephrol Dial Transplant. 1994;9(11):1590-4.
Abstract/Text One hundred twenty-eight patients with different renal diseases and chronic renal failure, stratified according to the underlying disease, were enrolled in a randomized controlled trial to investigate the effects on the rate of decline of renal function of two diets, a controlled protein diet (CPD) of 1 g protein/kg ideal body-weight (i.b.w.)/day, and a low-protein diet (LPD) of 0.6 g protein/kg i.b.w./day, given for 27.1 +/- 21.8 months. Dietary compliance was assessed by a dietary questionnaire, dietary interviews and measurement of 24-h urinary urea excretion. At the end of 6 months, actual mean protein intake was higher than expected (1.06 +/- 0.25 g/kg i.b.w./day) in CPD patients, and (0.80 +/- 0.21 g/kg i.b.w./day) in LPD patients: values were similar at 12 and 18 months after the time of enrollment. The end-point, defined as halving of creatinine clearance, was reached in 40% of patients on CPD, and in 28.6% of those on LPD (P = 0.038 by comparative life-table analysis). Multivariate regression analysis confirmed that CPD was associated with a higher risk of progression than LPD, and that two additional parameters (creatinine clearance at the time of randomization and average proteinuria during the follow-up) were significant independent risk factors, even more important than protein intake.

PMID 7870348
Vandana Menon, Joel D Kopple, Xuelei Wang, Gerald J Beck, Allan J Collins, John W Kusek, Tom Greene, Andrew S Levey, Mark J Sarnak
Effect of a very low-protein diet on outcomes: long-term follow-up of the Modification of Diet in Renal Disease (MDRD) Study.
Am J Kidney Dis. 2009 Feb;53(2):208-17. doi: 10.1053/j.ajkd.2008.08.009. Epub 2008 Oct 31.
Abstract/Text BACKGROUND: The long-term effect of a very low-protein diet on the progression of kidney disease is unknown. We examined the effect of a very low-protein diet on the development of kidney failure and death during long-term follow-up of the Modification of Diet in Renal Disease (MDRD) Study.
STUDY DESIGN: Long-term follow-up of study B of the MDRD Study (1989-1993).
SETTING & PARTICIPANTS: The MDRD Study examined the effects of dietary protein restriction and blood pressure control on progression of kidney disease. This analysis includes 255 trial participants with predominantly stage 4 nondiabetic chronic kidney disease.
INTERVENTION: A low-protein diet (0.58 g/kg/d) versus a very low-protein diet (0.28 g/kg/d) supplemented with a mixture of essential keto acids and amino acids (0.28 g/kg/d).
OUTCOMES: Kidney failure (initiation of dialysis therapy or transplantation) and all-cause mortality until December 31, 2000.
RESULTS: Kidney failure developed in 227 (89%) participants, 79 (30.9%) died, and 244 (95.7%) reached the composite outcome of either kidney failure or death. Median duration of follow-up until kidney failure, death, or administrative censoring was 3.2 years, and median time to death was 10.6 years. In the low-protein group, 117 (90.7%) participants developed kidney failure, 30 (23.3%) died, and 124 (96.1%) reached the composite outcome. In the very low-protein group, 110 (87.3%) participants developed kidney failure, 49 (38.9%) died, and 120 (95.2%) reached the composite outcome. After adjustment for a priori-specified covariates, hazard ratios were 0.83 (95% confidence interval, 0.62 to 1.12) for kidney failure, 1.92 (95% confidence interval, 1.15 to 3.20) for death, and 0.89 (95% confidence interval, 0.67 to 1.18) for the composite outcome in the very low-protein diet group compared with the low-protein diet group.
LIMITATIONS: Lack of dietary protein measurements during follow-up.
CONCLUSION: In long-term follow-up of the MDRD Study, assignment to a very low-protein diet did not delay progression to kidney failure, but appeared to increase the risk of death.

PMID 18950911
Charlotte Jones-Burton, Stephen L Seliger, Roberta W Scherer, Shiraz I Mishra, Ghazal Vessal, Jeanine Brown, Matthew R Weir, Jeffrey C Fink
Cigarette smoking and incident chronic kidney disease: a systematic review.
Am J Nephrol. 2007;27(4):342-51. doi: 10.1159/000103382. Epub 2007 May 23.
Abstract/Text BACKGROUND: Several studies have examined the role of cigarette smoking in the development of renal disease in human populations. However, there have been no systematic reviews on the evidence linking smoking with incident renal disease.
METHODS: We performed an evidence-based evaluation of peer-reviewed research published during 1966-2005, from a search of five databases, including Ovid MEDLINE and EMBASE.
RESULTS: Of the 28 studies that were reviewed, 11 were excluded from the final analysis due to poor methodological quality (n = 6), no reported risk estimate for the association between smoking and kidney disease (n = 3), inability to find a Japanese translator (n = 1), and duplicate cohort (n = 1). Seventeen studies were included in the final analysis; seven studies found an overall significant association between smoking and incident chronic kidney disease, and three studies found a significantly increased risk of chronic kidney disease in current smokers that was gender and/or dose related. An increased risk of developing chronic kidney disease among smokers was significantly associated with male gender (relative risk 2.4, 95% confidence interval 1.2-4.5), >20 cigarettes smoked/day (odds ratio 1.51, 95% confidence interval 1.06-2.15, and relative risk 2.3, 95% confidence interval 1.2-4.3), and smoking >40 years (odds ratio 1.45, 95% confidence interval 1.00-2.09). A pooled estimate of the relative risk (meta-analysis) was deemed inappropriate due to the heterogeneity in methodologies utilized by the different studies.
CONCLUSIONS: This comprehensive review reveals overall evidence for current cigarette smoking as a risk factor for incident chronic kidney disease. Further investigation is needed to more carefully examine the strength of the association between cigarette smoking and incident kidney disease.

Copyright 2007 S. Karger AG, Basel.
PMID 17541263
Ryohei Yamamoto, Yasuyuki Nagasawa, Tatsuya Shoji, Hirotsugu Iwatani, Takayuki Hamano, Noritaka Kawada, Kazunori Inoue, Takuya Uehata, Tetsuya Kaneko, Noriyuki Okada, Toshiki Moriyama, Masaru Horio, Atsushi Yamauchi, Yoshiharu Tsubakihara, Enyu Imai, Hiromi Rakugi, Yoshitaka Isaka
Cigarette smoking and progression of IgA nephropathy.
Am J Kidney Dis. 2010 Aug;56(2):313-24. doi: 10.1053/j.ajkd.2010.02.351. Epub 2010 May 14.
Abstract/Text BACKGROUND: Multiple community-based cohort studies of mainly middle-aged and elderly populations have shown that cigarette smoking is a risk factor for chronic kidney disease. However, little information is available about an effect of cigarette smoking on progression of primary kidney diseases, including immunoglobulin A (IgA) nephropathy.
STUDY DESIGN: Retrospective cohort study.
SETTING & PARTICIPANTS: 971 of 1,001 patients with a diagnosis of IgA nephropathy in 3 major nephrology centers in Osaka, Japan, between 1992 and 2005 who enrolled in the Study of Outcome and Practice Pattern of IgA Nephropathy (STOP-IgAN).
PREDICTORS: Smoking status and number of cigarettes smoked at the time of diagnosis using kidney biopsy. Dose-dependent associations between cigarette smoking and outcomes were assessed in multivariate Cox proportional hazards models. Significantly different clinical characteristics between non-/past and current smokers were controlled for using propensity score-based adjustment, stratification, and matching.
OUTCOMES: 50% increase in serum creatinine level as primary outcome. A composite outcome of a 100% increase in serum creatinine level or end-stage renal disease (ESRD) and ESRD alone as secondary outcomes.
RESULTS: During the median 5.8 years (interquartile range, 2.6-10.2) of the observational period, 117 participants progressed to a 50% increase in serum creatinine level and 47 advanced to ESRD. Multivariate Cox proportional hazards models identified current smokers (HR, 2.03 [95% CI, 1.33-3.10] for primary outcome) and number of cigarettes at kidney biopsy (HR, 1.21 [95% CI, 1.06-1.39] per 10 cigarettes per day) as significant predictors of outcomes. Propensity score-based models confirmed these results. Tests for interaction showed that the association of current smoking with adverse outcomes was stronger in those with lower compared with higher estimated glomerular filtration rates.
LIMITATION: Baseline smoking status was not verified using biochemical tests. Smoking status during the observational period was unavailable.
CONCLUSIONS: Cigarette smoking, in a dose-dependent manner, was identified as a key prognostic factor in IgA nephropathy. Smoking cessation should be encouraged as part of the treatment for IgA nephropathy.

Crown Copyright (c) 2010. Published by Elsevier Inc. All rights reserved.
PMID 20471735
Juhani Myllymäki, Jaana Syrjänen, Heikki Helin, Amos Pasternack, Anna Kattainen, Jukka Mustonen
Vascular diseases and their risk factors in IgA nephropathy.
Nephrol Dial Transplant. 2006 Jul;21(7):1876-82. doi: 10.1093/ndt/gfl062. Epub 2006 Mar 7.
Abstract/Text BACKGROUND: Many studies have focused on risk factors for renal insufficiency in IgA nephropathy (IgAN). We recently found metabolic factors, especially uric acid, to predict progression and marked histopathological lesions in IgAN. Since vascular diseases (VDs), in addition to renal insufficiency, affect the overall survival of IgAN patients, we studied the occurrence of and risk factors underlying VDs in IgAN.
METHODS: In this study, VDs here comprised the presence of coronary heart disease (CHD) and/or cerebrovascular disease (CeVD). We correlated clinical, metabolic and histopathological findings with the occurrence of VDs in 221 adult patients with IgAN. Seven histopathological parameters were semiquantitatively graded. Logistic regression analysis was used to evaluate independent predictors of VDs in these patients. The occurrence of VDs in IgAN patients > or = 30 years of age was studied and compared with that in the general population drawn from the same area.
RESULTS: VDs were notably common in IgAN patients. Patients with IgAN had significantly more frequent VDs, CHD and CeVD than the general population (P < 0.01 to < 0.001). Of > or = 30 years of age IgAN patients, 25% had some VD at the end of follow-up, while only 9% of the general population had VDs [odds ratio, OR 4.6 (2.2-9.4)]. Old age, male gender, hypertension, proteinuria, renal insufficiency, hyperuricaemia, hypertriglyceridaemia, diabetes, smoking and high body mass index correlated with the occurrence of VDs in univariate analysis. In all patients initial renal insufficiency and smoking were independently associated with some VD, male gender with CHD and hypertension with CeVD. In the multivariate analysis model including patients with initially normal renal function, male gender was independently associated with some VD, and hypertriglyceridaemia with CHD.
CONCLUSION: VDs, especially CeVD, would seem to be particularly common in patients with IgAN. Patients with progressive renal disease run a significantly elevated risk of developing VD. Many previously known risk factors for VD were also associated with the occurrence of some VD in the present study. Vascular changes seen in renal biopsy in patients with IgAN signify an elevated risk of VDs.

PMID 16522659
Abstract/Text
PMID 17136030
Kati Kaartinen, Onni Niemela, Jaana Syrjanen, Ilkka Porsti, Aimo Harmoinen, Amos Pasternack, Heini Huhtala, Jukka Mustonen
Alcohol consumption and kidney function in IgA glomerulonephritis.
Nephron Clin Pract. 2009;112(2):c86-93. doi: 10.1159/000213086. Epub 2009 Apr 18.
Abstract/Text BACKGROUND: IgA glomerulonephritis (IgAGN) is a kidney disease with variable prognosis. Several known risk factors exist for a more progressive course. Some population studies indicate that moderate alcohol consumption might protect kidney function, but the relationship between alcohol intake and IgAGN has not previously been examined.
METHODS: We examined 158 (95 men) IgAGN patients (37 abstainers, 80 light drinkers, 25 moderate drinkers and 16 heavy drinkers) in a cross-sectional study. The definition of alcohol consumption was based on interviews on the amounts of alcohol intake combined with measurements of serum carbohydrate-deficient transferrin, a specific biomarker of alcohol abuse. Longitudinal data on renal function were available from 117 patients (76 men) in whom an analysis with respect to progression was also performed.
RESULTS: Moderate drinkers showed the best kidney function. When adjusted by hypertension and 24-hour protein excretion, moderate alcohol consumption in a cross-sectional multivariate analysis, and both light and moderate alcohol consumption in a longitudinal multivariate analysis were significant factors of better kidney function. When the study population was divided by gender, the best kidney function was among light drinkers in women and among moderate drinkers in men.
CONCLUSIONS: Moderate alcohol consumption might have a favorable impact on the progression of IgAGN. Light alcohol consumption in women and moderate consumption in men are associated with improved indices of the glomerular filtration estimates in patients with IgAGN.

Copyright (c) 2009 S. Karger AG, Basel.
PMID 19390207
T H Jafar, C H Schmid, M Landa, I Giatras, R Toto, G Remuzzi, G Maschio, B M Brenner, A Kamper, P Zucchelli, G Becker, A Himmelmann, K Bannister, P Landais, S Shahinfar, P E de Jong, D de Zeeuw, J Lau, A S Levey
Angiotensin-converting enzyme inhibitors and progression of nondiabetic renal disease. A meta-analysis of patient-level data.
Ann Intern Med. 2001 Jul 17;135(2):73-87.
Abstract/Text PURPOSE: To examine the efficacy of ACE inhibitors for treatment of nondiabetic renal disease.
DATA SOURCES: 11 randomized, controlled trials comparing the efficacy of antihypertensive regimens including ACE inhibitors to the efficacy of regimens without ACE inhibitors in predominantly nondiabetic renal disease.
STUDY SELECTION: Studies were identified by searching the MEDLINE database for English-language studies evaluating the effects of ACE inhibitors on renal disease in humans between May 1977 (when ACE inhibitors were approved for trials in humans) and September 1997.
DATA EXTRACTION: Data on 1860 nondiabetic patients were analyzed.
DATA SYNTHESIS: Mean duration of follow-up was 2.2 years. Patients in the ACE inhibitor group had a greater mean decrease in systolic and diastolic blood pressure (4.5 mm Hg [95% CI, 3.0 to 6.1 mm Hg]) and 2.3 mm Hg [CI, 1.4 to 3.2 mm Hg], respectively) and urinary protein excretion (0.46 g/d [CI, 0.33 to 0.59 g/d]). After adjustment for patient and study characteristics at baseline and changes in systolic blood pressure and urinary protein excretion during follow-up, relative risks in the ACE inhibitor group were 0.69 (CI, 0.51 to 0.94) for end-stage renal disease and 0.70 (CI, 0.55 to 0.88) for the combined outcome of doubling of the baseline serum creatinine concentration or end-stage renal disease. Patients with greater urinary protein excretion at baseline benefited more from ACE inhibitor therapy (P = 0.03 and P = 0.001, respectively), but the data were inconclusive as to whether the benefit extended to patients with baseline urinary protein excretion less than 0.5 g/d.
CONCLUSION: Antihypertensive regimens that include ACE inhibitors are more effective than regimens without ACE inhibitors in slowing the progression of nondiabetic renal disease. The beneficial effect of ACE inhibitors is mediated by factors in addition to decreasing blood pressure and urinary protein excretion and is greater in patients with proteinuria. Angiotensin-converting inhibitors are indicated for treatment of nondiabetic patients with chronic renal disease and proteinuria and, possibly, those without proteinuria.

PMID 11453706
Manuel Praga, Eduardo Gutiérrez, Ester González, Enrique Morales, Eduardo Hernández
Treatment of IgA nephropathy with ACE inhibitors: a randomized and controlled trial.
J Am Soc Nephrol. 2003 Jun;14(6):1578-83.
Abstract/Text Some retrospective studies have suggested a beneficial influence of angiotensin-converting enzyme (ACE) inhibitors on the progression of IgA nephropathy (IgAN), but prospective and controlled studies demonstrating this effect are lacking. Forty-four patients with biopsy-proven IgAN, proteinuria > or = 0.5 g/d, and serum creatinine (SCr) < or = 1.5 mg/dl were randomly assigned either to receive enalapril (n = 23) or to a control group (n = 21) in whom BP was controlled with antihypertensives other than ACE inhibitors. Primary outcome was renal survival estimated by a 50% increase in baseline SCr. Secondary outcomes were the presence of a SCr > 1.5 mg/dl at the last visit and the evolution of proteinuria. Baseline clinical findings were similar at baseline between enalapril-treated and control group, and there were no differences in BP control during follow-up. Mean follow-up was 78 +/- 37 mo in the enalapril group and 74 +/- 36 mo in the control group. Three patients (13%) in the enalapril group and 12 (57%) in the control group reached the primary end point (P < 0.05). Kaplan-Meier renal survival was significantly better in enalapril group than in control group: 100% versus 70% after 4 yr and 92% versus 55% after 7 yr (P < 0.05). Three patients in the enalapril group (13%) and 11 (52%) in the control group showed SCr > 1.5 mg/dl at the last visit (P < 0.05). Proteinuria significantly decreased in the enalapril group, whereas it tended to increase in the control group (P < 0.001 between groups). In conclusion, ACE inhibitors significantly improve renal survival in proteinuric IgAN with normal or moderately reduced renal function.

PMID 12761258
Rosanna Coppo, Licia Peruzzi, Alessandro Amore, Antonio Piccoli, Pierre Cochat, Rosario Stone, Martin Kirschstein, Tommy Linné
IgACE: a placebo-controlled, randomized trial of angiotensin-converting enzyme inhibitors in children and young people with IgA nephropathy and moderate proteinuria.
J Am Soc Nephrol. 2007 Jun;18(6):1880-8. doi: 10.1681/ASN.2006040347. Epub 2007 May 18.
Abstract/Text This European Community Biomedicine and Health Research-supported, multicenter, randomized, placebo-controlled, double-blind trial investigated the effect of an angiotensin-converting enzyme inhibitor (ACE-I) in children and young people with IgA nephropathy (IgAN), moderate proteinuria (>1 and <3.5 g/d per 1.73 m(2)) and creatinine clearance (CrCl) >50 ml/min per 1.73 m(2). Sixty-six patients who were 20.5 yr of age (range 9 to 35 yr), were randomly assigned to Benazepril 0.2 mg/kg per d (ACE-I) or placebo and were followed for a median of 38 mo. The primary outcome was the progression of kidney disease, defined as >30% decrease of CrCl; secondary outcomes were (1) a composite end point of >30% decrease of CrCl or worsening of proteinuria until > or =3.5 g/d per 1.73 m(2) and (2) proteinuria partial remission (<0.5 g/d per 1.73 m(2)) or total remission (<160 mg/d per 1.73 m(2)) for >6 mo. Analysis was by intention to treat. A single patient (3.1%) in the ACE-I group and five (14.7%) in the placebo group showed a worsening of CrCl >30%. The composite end point of >30% decrease of CrCl or worsening of proteinuria until nephrotic range was reached by one (3.1%) of 32 patients in the ACE-I group, and nine (26.5%) of 34 in the placebo group; the difference was significant (log-rank P = 0.035). A stable, partial remission of proteinuria was observed in 13 (40.6%) of 32 patients in the ACE-I group versus three (8.8%) of 34 in the placebo group (log-rank P = 0.033), with total remission in 12.5% of ACE-I-treated patients and in none in the placebo group (log-rank P = 0.029). The multivariate Cox analysis showed that treatment with ACE-I was the independent predictor of prognosis; no influence on the composite end point was found for gender, age, baseline CrCl, systolic or diastolic BP, mean arterial pressure, or proteinuria.

PMID 17513327
Yoshinori Taji, Takashi Kuwahara, Satoru Shikata, Takeshi Morimoto
Meta-analysis of antiplatelet therapy for IgA nephropathy.
Clin Exp Nephrol. 2006 Dec;10(4):268-73. doi: 10.1007/s10157-006-0433-8. Epub 2006 Dec 20.
Abstract/Text BACKGROUND: Antiplatelet agents have been widely used in the management of immunoglobulin A (IgA) nephropathy in the Japanese population. To systematically evaluate the effects of antiplatelet agents for IgA nephropathy, we conducted a meta-analysis of the published studies.
METHODS: Data sources consisted of MEDLINE, EMBASE, the Cochrane Library, Ityu-shi (Japanese medical database), and bibliographies from the studies. The quality of the studies was evaluated from the intention to treat analysis and allocation concealment, as well as by the Jadad method. Meta-analyses were performed on the outcomes of proteinuria and renal function.
RESULTS: Seven articles met the predetermined inclusion criteria. The use of antiplatelet agents showed statistically significant effects on proteinuria and renal function. The pooled risk ratio for proteinuria was 0.61 (95% confidence intervals (CI) 0.39-0.94) and for renal function it was 0.74 (95% CI 0.63-0.87).
CONCLUSIONS: Antiplatelet agents resulted in reduced proteinuria and protected renal function in patients with IgA nephropathy. However, studies of high-quality design were rare, and most studies assessed surrogate outcomes. More properly designed studies are needed to reach a definitive assessment of this matter.

PMID 17186331
Claudio Pozzi, Simeone Andrulli, Lucia Del Vecchio, Patrizia Melis, Giovanni B Fogazzi, Paolo Altieri, Claudio Ponticelli, Francesco Locatelli
Corticosteroid effectiveness in IgA nephropathy: long-term results of a randomized, controlled trial.
J Am Soc Nephrol. 2004 Jan;15(1):157-63.
Abstract/Text Proteinuria plays a causal role in the progression of IgA nephropathy (IgAN). A previous controlled trial showed that steroids are effective in reducing proteinuria and preserving renal function in patients with IgAN. The objective of this study was to evaluate the long-term effectiveness of steroids in IgAN, examine the trend of proteinuria during follow-up (starting from the hypothesis that the degree of reduction in proteinuria may influence IgAN outcome), and evaluate how histologic scores can influence steroid response. A secondary analysis of a multicenter, randomized, controlled trial of 86 adult IgAN patients who were receiving supportive therapy or intravenous methylprednisolone plus oral prednisone for 6 mo was conducted. Ten-year renal survival was significantly better in the steroid than in the control group (97% versus 53%; log rank test P = 0.0003). In the 72 patients who did not reach the end point (doubling in baseline serum creatinine), median proteinuria significantly decreased (1.9 g/24 h at baseline, 1.1 g/24 h after 6 mo, and 0.6 g/24 h after a median of 7 yr). In the 14 progressive patients, proteinuria increased from a median of 1.7 g/24 h at baseline to 2.0 g/24 h after 6 mo and 3.3 g/24 h after a median of 5 yr. Steroids were effective in every histologic class. Cox multivariate regression analyses showed that, in addition to steroids, a low baseline histologic score, a reduction in proteinuria after 6 mo, and no increase in proteinuria during follow-up all were independent predictors of a beneficial outcome. Steroids significantly reduce proteinuria and protect against renal function deterioration in IgAN. The histologic picture and proteinuria during early and late follow-up improve the prediction of outcome, but considerable variability remains outside the model.

PMID 14694168
Joshua A Samuels, Giovanni F M Strippoli, Jonathan C Craig, Francesco P Schena, Donald A Molony
Immunosuppressive treatments for immunoglobulin A nephropathy: a meta-analysis of randomized controlled trials.
Nephrology (Carlton). 2004 Aug;9(4):177-85. doi: 10.1111/j.1440-1797.2004.00255.x.
Abstract/Text Immunoglobulin A (IgA) nephropathy is a worldwide disease that causes end-stage kidney disease (ESRD) in up to 15-20% of affected patients within 10 years from the apparent onset of disease and in up to 30-40% of individuals within 20 years from diagnosis. No specific treatment has been established and there is wide variation in current practice. This systematic review evaluates the use of immunosuppressive agents to treat patients with IgA nephropathy. The Cochrane Renal Group Specialized Register, Cochrane Controlled Trial Registry, MEDLINE, EMBASE and article reference lists were searched for randomized or quasi randomized trials. Two independent reviewers assessed studies for inclusion criteria (biopsy proven IgA nephropathy, randomized trial, use of immunosuppressive agents) and extracted data regarding the effects of immunosuppressive agents on ESRD, doubling of serum creatinine, glomerular filtration rate, urinary protein excretion and side-effects. Data were analysed with a random effects model. The published trials were few (13 trials, 623 patients) and were generally of poor quality. Compared with placebo, steroids were associated with a lower risk of progression to ESRD (six trials, 341 patients, RR 0.44, 95% CI 0.25-0.80) and lower end-of-trial proteinuria (six trials, 263 patients, weighted mean difference (WMD) -0.49 g/day, 95% CI -0.25 to -0.72). Treatment with alkylating agents significantly reduced end of treatment proteinuria (two trials, 122 patients, WMD -0.94, 95% CI -0.46 to -1.43). Although the optimal management of patients with IgA nephropathy remains uncertain because of limitations with the existing published data, immunosuppressive agents are a promising strategy and should be investigated further.

PMID 15363047

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