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Daniel C Cattran - One of the best experts on this subject based on the ideXlab platform.

  • reproducibility of the oxford clAssificAtion of Immunoglobulin A nephropAthy impAct of biopsy scoring on treAtment AllocAtion And clinicAl relevAnce of disAgreements evidence from the vAlidAtion of igA study cohort
    Nephrology Dialysis Transplantation, 2019
    Co-Authors: Shubha Bellur, Daniel C Cattran, Rosanna Coppo, Ian S D Roberts, Stephan Troyanov, Virginie Royal, Terence H Cook, Yolanda Arce Terroba, Anna Maria Asunis, Ingeborg M Bajema
    Abstract:

    BAckground The VALidAtion of IGA (VALIGA) study investigAted the utility of the Oxford ClAssificAtion of Immunoglobulin A nephropAthy (IgAN) in 1147 pAtients from 13 EuropeAn countries. Methods. Biopsies were scored by locAl pAthologists followed by centrAl review in Oxford. We hAd two distinct objectives: to Assess how closely pAthology findings were AssociAted with the decision to give corticosteroid/immunosuppressive (CS/IS) treAtments, And to determine the impAct of differences in MEST-C scoring between centrAl And locAl pAthologists on the clinicAl vAlue of the Oxford ClAssificAtion. We tested for eAch lesion the AssociAtions between the type of Agreement (locAl And centrAl pAthologists scoring Absent, locAl present And centrAl Absent, locAl Absent And centrAl present, both scoring present) with the initiAl clinicAl Assessment, As well As long-term outcomes in those pAtients who did not receive CS/IS. Results All glomerulAr lesions (M, E, C And S) Assessed by locAl pAthologists were independently AssociAted with the decision to Administer CS/IS therApy, while the severity of tubulointerstitiAl lesions wAs not. Reproducibility between locAl And centrAl pAthologists wAs moderAte for S (segmentAl sclerosis) And T (tubulAr Atrophy/interstitiAl fibrosis), And poor for M (mesAngiAl hypercellulArity), E (endocApillAry hypercellulArity) And C (crescents). LocAl pAthologists found stAtisticAlly more of eAch lesion, except for the S lesion, which wAs more frequent with centrAl review. DisAgreements were more likely to occur when the proportion of glomeruli Affected wAs low. The M lesion, Assessed by centrAl pAthologists, correlAted better with the severity of the diseAse At presentAtion And discriminAted better with outcomes. In contrAst, the E lesion, evAluAted by locAl pAthologists, correlAted better with the clinicAl presentAtion And outcomes when compAred with centrAl review. Both C And S lesions, when discordAnt between locAl And centrAl pAthologists, hAd A clinicAl phenotype intermediAte to double Absent lesions (milder diseAse) And double present (more severe). Conclusion We conclude thAt differences in the scoring of MEST-C criteriA between locAl pAthologists And A centrAl reviewer hAve A significAnt impAct on the prognostic vAlue of the Oxford ClAssificAtion. Since the decision to offer immunosuppressive therApy in this cohort wAs intimAtely AssociAted with the MEST-C score, this study indicAtes A need for A more detAiled guidAnce for pAthologists in the scoring of IgAN biopsies.

  • risk fActors for progression in children And young Adults with igA nephropAthy An AnAlysis of 261 cAses from the vAligA europeAn cohort
    Pediatric Nephrology, 2017
    Co-Authors: Rosanna Coppo, Daniel C Cattran, Roberta Camilla, Alessandro Amore, Licia Peruzzi, Shubha Bellur, Ian S D Roberts, Terence H Cook, Danilo Lofaro, Francesco Emma
    Abstract:

    BAckground There is A need for eArly identificAtion of children with Immunoglobulin A nephropAthy (IgAN) At risk of progression of kidney diseAse.

  • long term benefits of Angiotensin converting enzyme inhibitor therApy in pAtients with severe Immunoglobulin A nephropAthy A compArison to pAtients receiving treAtment with other Antihypertensive Agents And to pAtients receiving no therApy
    American Journal of Kidney Diseases, 1994
    Co-Authors: Daniel C Cattran, Celia M T Greenwood, Susan Ritchie
    Abstract:

    Of 531 cAses of Immunoglobulin A nephropAthy in the Toronto Glomerulonephritis Registry, 115 were determined by retrospective AnAlysis to hAve proteinuriA ± 1 g/d. These pAtients hAve been followed A minimum of 3 months (rAnge, 3 to 121 months). Monitoring in the registry included routine blood pressure estimAtes And renAl function stAtus by serum creAtinine, creAtinine cleArAnce, And proteinuriA. These pAtients were grouped And exAmined retrospectively into three cAtegories (1) hypertensive on Angiotensin-converting enzyme (ACE) inhibitor therApy (ACE l ), (2) hypertensive on other medicAtion, And (3) no hypertension (NT). Despite compArAble renAl function AbnormAlities, the 27 ACE, pAtients, when compAred with the 55 pAtients receiving other medicAtion, experienced A significAntly slower rAte of decline in renAl function As meAsured by slope of creAtinine cleArAnce (-0.4 mL/min/mo v -1.0 mL/min/mo; P = 0.007), longer time to A loss of one third of bAseline creAtinine cleArAnce ( P = 0.004), And A higher percentAge of remission in proteinuriA (18.5% v 1.8%; P = 0.003). A subsequent compArison wAs mAde between the NT And ACE l groups And, despite A much lower initiAl serum creAtinine, less severe pAthology, And A longer observAtion period in the NT group, both the rAte of decline of creAtinine cleArAnce (-0.5 mL/min/mo v -0.4 mL/min/mo; P = 0.9) And the percentAge of pAtients progressing to renAl fAilure (21.2% v 18.5; P = 0.8) were not different. The remission rAte of proteinuriA wAs superior in the ACE l -treAted group compAred with the NT group. MultivAriAte AnAlysis, controlling for differences in initiAl renAl function And proteinuriA And weighting slopes for vAriAbility in observAtion time And precision, does not Affect these results. This long-term retrospective review suggests thAt ACE l therApy is superior to other Antihypertensive Agents in stAbilizing creAtinine cleArAnce And improving proteinuriA in pAtients with severe Immunoglobulin A nephropAthy.

  • long term benefits of Angiotensin converting enzyme inhibitor therApy in pAtients with severe Immunoglobulin A nephropAthy A compArison to pAtients receiving treAtment with other Antihypertensive Agents And to pAtients receiving no therApy
    American Journal of Kidney Diseases, 1994
    Co-Authors: Daniel C Cattran, Celia M T Greenwood, Susan Ritchie
    Abstract:

    Of 531 cAses of Immunoglobulin A nephropAthy in the Toronto Glomerulonephritis Registry, 115 were determined by retrospective AnAlysis to hAve proteinuriA > or = 1 g/d. These pAtients hAve been followed A minimum of 3 months (rAnge, 3 to 121 months). Monitoring in the registry included routine blood pressure estimAtes And renAl function stAtus by serum creAtinine, creAtinine cleArAnce, And proteinuriA. These pAtients were grouped And exAmined retrospectively into three cAtegories (1) hypertensive on Angiotensin-converting enzyme (ACE) inhibitor therApy (ACEi), (2) hypertensive on other medicAtion, And (3) no hypertension (NT). Despite compArAble renAl function AbnormAlities, the 27 ACEi pAtients, when compAred with the 55 pAtients receiving other medicAtion, experienced A significAntly slower rAte of decline in renAl function As meAsured by slope of creAtinine cleArAnce (-0.4 mL/min/mo v-1.0 mL/min/mo; P = 0.007), longer time to A loss of one third of bAseline creAtinine cleArAnce (P = 0.004), And A higher percentAge of remission in proteinuriA (18.5% v 1.8%; P = 0.003). A subsequent compArison wAs mAde between the NT And ACEi groups And, despite A much lower initiAl serum creAtinine, less severe pAthology, And A longer observAtion period in the NT group, both the rAte of decline of creAtinine cleArAnce (-0.5 mL/min/mo v -0.4 mL/min/mo; P = 0.9) And the percentAge of pAtients progressing to renAl fAilure (21.2% v 18.5; P = 0.8) were not different. The remission rAte of proteinuriA wAs superior in the ACEi-treAted group compAred with the NT group.(ABSTRACT TRUNCATED AT 250 WORDS)

Rosanna Coppo - One of the best experts on this subject based on the ideXlab platform.

  • the switch from proteAsome to immunoproteAsome is increAsed in circulAting cells of pAtients with fAst progressive Immunoglobulin A nephropAthy And AssociAted with defective cd46 expression
    Nephrology Dialysis Transplantation, 2021
    Co-Authors: Licia Peruzzi, Rosanna Coppo, Elisa Loiacono, Massimilano Bergallo, Alexandra Krutova, Maria Luisa Russo, Enrico Cocchi, Monica Bodria, Luca Vergano, Alessandro Amore
    Abstract:

    The proteAsome to immunoproteAsome (iPS) switch consists of β1, β2 And β5 subunit replAcement by low moleculAr weight protein 2 (LMP2), LMP7 And multicAtAlytic endopeptidAse-like complex-1 (MECL1) subunits, resulting in A more efficient peptide prepArAtion for mAjor histocompAtibility complex 1 (MHC-I) presentAtion. It is ActivAted by toll-like receptor (TLR) Agonists And interferons And mAy Also be influenced by genetic vAriAtion. In A previous study we found An iPS upregulAtion in peripherAl cells of pAtients with Immunoglobulin A nephropAthy (IgAN). We Aimed to investigAte in 157 IgAN pAtients enrolled through the multinAtionAl VAlidAtion Study of the Oxford ClAssificAtion of IgAN (VALIGA) study the relAtionships between iPS switch And estimAted glomerulAr filtrAtion rAte (eGFR) modificAtions from renAl biopsy to sAmpling. PAtients hAd A previous long follow-up (6.4 yeArs in mediAn) thAt Allowed An AccurAte cAlculAtion of their slope of renAl function decline. We Also evAluAted the effects of the PSMB8/PSMB9 locus (rs9357155) AssociAted with IgAN in genome-wide AssociAtion studies And the expression of messenger RNAs (mRNAs) encoding for TLRs And CD46, A C3 convertAse inhibitor, Acting Also on T-regulAtory cell promotion, found to hAve reduced expression in progressive IgAN. We detected An upregulAtion of LMP7/β5 And LMP2/β1 switches. We observed no genetic effect of rs9357155. TLR4 And TLR2 mRNAs were found to be significAntly AssociAted with iPS switches, pArticulArly TLR4 And LMP7/β5 (P 75th centile, i.e. -1.91 mL/min/1.73 m2/yeAr) were chArActerized by significAntly elevAted LMP7/β5 mRNA (P = 0.04) And low CD46 mRNA expression (P < 0.01). A multivAriAte logistic regression model, cAtegorizing pAtients by different levels of kidney diseAse progression, showed A high prediction vAlue for the combinAtion of high LMP7/β5 And low CD46 expression.

  • glomerulAr endotheliAl ActivAtion c4d deposits And microAngiopAthy in Immunoglobulin A nephropAthy
    Nephrology Dialysis Transplantation, 2021
    Co-Authors: Hernan Trimarchi, Rosanna Coppo
    Abstract:

    Immunoglobulin A nephropAthy (IgAN) is considered As mesAngiopAthy since it initiAtes in the mesAngium; however, other glomerulAr components Are involved And the glomerulAr cApillAry wAll offers the first contAct to circulAting mAcromoleculAr IgA1. Acute And Active forms of IgAN Are AssociAted with endocApillAry hypercellulArity And vAsculAr dAmAge of vArious degrees, in severe cAses with microAngiopAthy (MA) without or with thrombosis [thrombotic microAngiopAthy (TMA)]. VAsculAr dAmAge ActivAtes complement And coAgulAtion cAscAdes. A defective complement regulAtion hAs recently been detected in Active And progressive cAses of IgAN. C4d deposits in renAl biopsies hAve been found to be An eArly risk fActor. These observAtions hAve rAised interest in mAnifestAtion of MA And TMA in progressive cAses of IgAN. MA-TMA lesions hAve been found in vArious percentAges (2-53%) of pAtients with IgAN According to pAtients' selection And pAthology definition of TMA. The AssociAtion with hypertension (HTN) wAs so strong thAt it led to the hypothesis thAt MA/TMA in IgAN wAs A mere consequence of severe HTN. Old And new clinicAl And experimentAl dAtA indicAte thAt in IgAN the interAction of the glomerulAr cApillAry wAll with immune reActAnts And complement uncontrolled ActivAtion leAding to C4b deposits fAvours the development of MA-TMA, which plAys A role in progression And renAl function decline. The centrAl role of complement ActivAtion is relevAnt Also for the new therApeutic interventions offered by the phArmA.

  • reproducibility of the oxford clAssificAtion of Immunoglobulin A nephropAthy impAct of biopsy scoring on treAtment AllocAtion And clinicAl relevAnce of disAgreements evidence from the vAlidAtion of igA study cohort
    Nephrology Dialysis Transplantation, 2019
    Co-Authors: Shubha Bellur, Daniel C Cattran, Rosanna Coppo, Ian S D Roberts, Stephan Troyanov, Virginie Royal, Terence H Cook, Yolanda Arce Terroba, Anna Maria Asunis, Ingeborg M Bajema
    Abstract:

    BAckground The VALidAtion of IGA (VALIGA) study investigAted the utility of the Oxford ClAssificAtion of Immunoglobulin A nephropAthy (IgAN) in 1147 pAtients from 13 EuropeAn countries. Methods. Biopsies were scored by locAl pAthologists followed by centrAl review in Oxford. We hAd two distinct objectives: to Assess how closely pAthology findings were AssociAted with the decision to give corticosteroid/immunosuppressive (CS/IS) treAtments, And to determine the impAct of differences in MEST-C scoring between centrAl And locAl pAthologists on the clinicAl vAlue of the Oxford ClAssificAtion. We tested for eAch lesion the AssociAtions between the type of Agreement (locAl And centrAl pAthologists scoring Absent, locAl present And centrAl Absent, locAl Absent And centrAl present, both scoring present) with the initiAl clinicAl Assessment, As well As long-term outcomes in those pAtients who did not receive CS/IS. Results All glomerulAr lesions (M, E, C And S) Assessed by locAl pAthologists were independently AssociAted with the decision to Administer CS/IS therApy, while the severity of tubulointerstitiAl lesions wAs not. Reproducibility between locAl And centrAl pAthologists wAs moderAte for S (segmentAl sclerosis) And T (tubulAr Atrophy/interstitiAl fibrosis), And poor for M (mesAngiAl hypercellulArity), E (endocApillAry hypercellulArity) And C (crescents). LocAl pAthologists found stAtisticAlly more of eAch lesion, except for the S lesion, which wAs more frequent with centrAl review. DisAgreements were more likely to occur when the proportion of glomeruli Affected wAs low. The M lesion, Assessed by centrAl pAthologists, correlAted better with the severity of the diseAse At presentAtion And discriminAted better with outcomes. In contrAst, the E lesion, evAluAted by locAl pAthologists, correlAted better with the clinicAl presentAtion And outcomes when compAred with centrAl review. Both C And S lesions, when discordAnt between locAl And centrAl pAthologists, hAd A clinicAl phenotype intermediAte to double Absent lesions (milder diseAse) And double present (more severe). Conclusion We conclude thAt differences in the scoring of MEST-C criteriA between locAl pAthologists And A centrAl reviewer hAve A significAnt impAct on the prognostic vAlue of the Oxford ClAssificAtion. Since the decision to offer immunosuppressive therApy in this cohort wAs intimAtely AssociAted with the MEST-C score, this study indicAtes A need for A more detAiled guidAnce for pAthologists in the scoring of IgAN biopsies.

  • podocytopAthy in the mesAngiAl proliferAtive Immunoglobulin A nephropAthy new insights into the mechAnisms of dAmAge And progression
    Nephrology Dialysis Transplantation, 2019
    Co-Authors: Hernan Trimarchi, Rosanna Coppo
    Abstract:

    Immunoglobulin A nephropAthy (IgAN) wAs defined As A mesAngiopAthic diseAse, since the primAry site of deposition of IgA immune mAteriAl is the mesAngium, And proliferAtion of mesAngiAl cells And mAtrix excess deposition Are the first histopAthologic lesions. However, the relentless silent progression of IgAN is mostly due to the development of persistent proteinuriA, And recent studies indicAte thAt A mAjor role is plAyed by previous dAmAge of function And AnAtomy of podocytes. In IgAN, the podocytopAthic chAnges Are the consequence of initiAl AlterAtions in the mesAngiAl AreA with AccumulAtion of IgA contAining immune mAteriAl. Podocytes Are therefore Affected by interActions of messAges originAlly driven from the mesAngium. After continuous insult, podocytes detAch from the glomerulAr bAsement membrAne. This podocytopAthy fAvours not only the development of glomerulAr focAl And segmentAl sclerosis, but Also the progressive renAl function loss. It is still debAted whether these lesions cAn be prevented or cured by corticosteroid/immunosuppressive treAtment. We Aimed to review recent dAtA on the mechAnisms implicAted in the podocytopAthy present in IgAN, showing new moleculAr risk fActors for progression of this diseAse. Moreover, these observAtions mAy indicAte thAt the tArget for new drugs is not only focused on decreAsing the Activity of mesAngiAl cells And inflAmmAtory reActions in IgAN, but Also on improving podocyte function And survivAl.

  • defective gene expression of the membrAne complement inhibitor cd46 in pAtients with progressive Immunoglobulin A nephropAthy
    Nephrology Dialysis Transplantation, 2019
    Co-Authors: Rosanna Coppo, Alessandro Amore, Licia Peruzzi, Sigrid Lundberg, Elisa Loiacono, Massimilano Bergallo, Alexandra Krutova, Maria Luisa Russo, Enrico Cocchi, Dita Maixnerova
    Abstract:

    BAckground Complement is thought to plAy A role in Immunoglobulin A nephropAthy (IgAN), though the ActivAting mechAnisms Are unknown. This study focused on the gene expression of CD46 And CD55, two key molecules for regulAting C3 convertAse Activity of lectin And AlternAtive complement pAthwAys At A cellulAr level. Methods The trAnscriptionAl expression in peripherAl white blood cells (WBCs) of CD46 And CD55 wAs investigAted in 157 pAtients enrolled by the VAlidAtion of the Oxford ClAssificAtion of IgAN group, looking for correlAtions with clinicAl And pAthology feAtures And estimAted glomerulAr filtrAtion rAte (eGFR) modificAtions from renAl biopsy to sAmpling. PAtients hAd A previous mediAn follow-up of 6.4 (interquArtile rAnge 2.8-10.7) yeArs And were divided into progressors And non-progressors According to the mediAn vAlue of their velocity of loss of renAl function per yeAr (-0.41 mL/min/1.73 m2/yeAr). Results CD46 And CD55 messenger RNA (mRNA) expression in WBCs wAs not correlAted with eGFR vAlues or proteinuriA At sAmpling. CD46 mRNA wAs significAntly correlAted with eGFR decline rAte As A continuous outcome vAriAble (P = 0.014). A significAnt difference wAs found in CD46 gene expression between progressors And non-progressors (P = 0.013). CD46 And CD55 mRNA levels were significAntly correlAted (P Conclusions PAtients with progressive IgAN showed lower expression of mRNA encoding for the complement inhibitory protein CD46, which mAy implicAte A defective regulAtion of C3 convertAse with uncontrolled complement ActivAtion.

Susan Ritchie - One of the best experts on this subject based on the ideXlab platform.

  • long term benefits of Angiotensin converting enzyme inhibitor therApy in pAtients with severe Immunoglobulin A nephropAthy A compArison to pAtients receiving treAtment with other Antihypertensive Agents And to pAtients receiving no therApy
    American Journal of Kidney Diseases, 1994
    Co-Authors: Daniel C Cattran, Celia M T Greenwood, Susan Ritchie
    Abstract:

    Of 531 cAses of Immunoglobulin A nephropAthy in the Toronto Glomerulonephritis Registry, 115 were determined by retrospective AnAlysis to hAve proteinuriA ± 1 g/d. These pAtients hAve been followed A minimum of 3 months (rAnge, 3 to 121 months). Monitoring in the registry included routine blood pressure estimAtes And renAl function stAtus by serum creAtinine, creAtinine cleArAnce, And proteinuriA. These pAtients were grouped And exAmined retrospectively into three cAtegories (1) hypertensive on Angiotensin-converting enzyme (ACE) inhibitor therApy (ACE l ), (2) hypertensive on other medicAtion, And (3) no hypertension (NT). Despite compArAble renAl function AbnormAlities, the 27 ACE, pAtients, when compAred with the 55 pAtients receiving other medicAtion, experienced A significAntly slower rAte of decline in renAl function As meAsured by slope of creAtinine cleArAnce (-0.4 mL/min/mo v -1.0 mL/min/mo; P = 0.007), longer time to A loss of one third of bAseline creAtinine cleArAnce ( P = 0.004), And A higher percentAge of remission in proteinuriA (18.5% v 1.8%; P = 0.003). A subsequent compArison wAs mAde between the NT And ACE l groups And, despite A much lower initiAl serum creAtinine, less severe pAthology, And A longer observAtion period in the NT group, both the rAte of decline of creAtinine cleArAnce (-0.5 mL/min/mo v -0.4 mL/min/mo; P = 0.9) And the percentAge of pAtients progressing to renAl fAilure (21.2% v 18.5; P = 0.8) were not different. The remission rAte of proteinuriA wAs superior in the ACE l -treAted group compAred with the NT group. MultivAriAte AnAlysis, controlling for differences in initiAl renAl function And proteinuriA And weighting slopes for vAriAbility in observAtion time And precision, does not Affect these results. This long-term retrospective review suggests thAt ACE l therApy is superior to other Antihypertensive Agents in stAbilizing creAtinine cleArAnce And improving proteinuriA in pAtients with severe Immunoglobulin A nephropAthy.

  • long term benefits of Angiotensin converting enzyme inhibitor therApy in pAtients with severe Immunoglobulin A nephropAthy A compArison to pAtients receiving treAtment with other Antihypertensive Agents And to pAtients receiving no therApy
    American Journal of Kidney Diseases, 1994
    Co-Authors: Daniel C Cattran, Celia M T Greenwood, Susan Ritchie
    Abstract:

    Of 531 cAses of Immunoglobulin A nephropAthy in the Toronto Glomerulonephritis Registry, 115 were determined by retrospective AnAlysis to hAve proteinuriA > or = 1 g/d. These pAtients hAve been followed A minimum of 3 months (rAnge, 3 to 121 months). Monitoring in the registry included routine blood pressure estimAtes And renAl function stAtus by serum creAtinine, creAtinine cleArAnce, And proteinuriA. These pAtients were grouped And exAmined retrospectively into three cAtegories (1) hypertensive on Angiotensin-converting enzyme (ACE) inhibitor therApy (ACEi), (2) hypertensive on other medicAtion, And (3) no hypertension (NT). Despite compArAble renAl function AbnormAlities, the 27 ACEi pAtients, when compAred with the 55 pAtients receiving other medicAtion, experienced A significAntly slower rAte of decline in renAl function As meAsured by slope of creAtinine cleArAnce (-0.4 mL/min/mo v-1.0 mL/min/mo; P = 0.007), longer time to A loss of one third of bAseline creAtinine cleArAnce (P = 0.004), And A higher percentAge of remission in proteinuriA (18.5% v 1.8%; P = 0.003). A subsequent compArison wAs mAde between the NT And ACEi groups And, despite A much lower initiAl serum creAtinine, less severe pAthology, And A longer observAtion period in the NT group, both the rAte of decline of creAtinine cleArAnce (-0.5 mL/min/mo v -0.4 mL/min/mo; P = 0.9) And the percentAge of pAtients progressing to renAl fAilure (21.2% v 18.5; P = 0.8) were not different. The remission rAte of proteinuriA wAs superior in the ACEi-treAted group compAred with the NT group.(ABSTRACT TRUNCATED AT 250 WORDS)

Rune Bjorneklett - One of the best experts on this subject based on the ideXlab platform.

  • long term outcome in 145 pAtients with Assumed benign Immunoglobulin A nephropAthy
    Nephrology Dialysis Transplantation, 2017
    Co-Authors: Thomas Knoop, Bjorn Egil Vikse, Angela Mwakimonga, Sabine Leh, Rune Bjorneklett
    Abstract:

    BAckground PAtients with Immunoglobulin A nephropAthy (IgAN) who present with mild to moderAte proteinuriA And normAl renAl function Are Assumed to hAve excellent short-term renAl prognosis, but the long-term prognosis is uncertAin. Methods PAtients were selected from the NorwegiAn Kidney Biopsy Registry bAsed on the following criteriA: diAgnostic renAl biopsy performed in the period 1988-99, with estimAted glomerulAr filtrAtion rAte (eGFR) ≥60 mL/min/1.73 m2 And proteinuriA Results A totAl of 145 pAtients Attended the exAminAtion, performed by the first Author, After A mediAn of 22 (interquArtile rAnge 19-25) yeArs After diAgnosis. At the exAminAtion, 27 pAtients (18.6%) hAd A ≥50% decreAse in GFR, of whom 4 (2.8%) hAd developed end-stAge renAl diseAse (ESRD). The meAn durAtion from renAl biopsy to ≥ 50% decreAse in GFR wAs 17.3 ± 5.1 yeArs in our cohort. ClinicAl remission wAs observed in 42 (29.0%) pAtients. RenAl biopsies were re-exAmined utilizing the Oxford clAssificAtion criteriA. MesAngiAl hypercellulArity wAs found in 12.3%, endocApillAry proliferAtion wAs detected in 10.7% And segmentAl glomerulosclerosis wAs observed in 23.8%. All biopsies were scored As T0 (tubulAr Atrophy in Conclusions We hAve shown thAt 18.6% of pAtients with Assumed benign IgAN hAd progressive diseAse After A mediAn durAtion of 22 yeArs And thAt these pAtients could not be predicted At the time of biopsy. Our study demonstrAtes thAt An extended follow-up period is needed when Assessing prognosis in this group of pAtients.

Takashi Takei - One of the best experts on this subject based on the ideXlab platform.

  • effect of hemAturiA on the outcome of Immunoglobulin A nephropAthy with proteinuriA
    Journal of nephropathology, 2016
    Co-Authors: Chihiro Iwasaki, Takashi Takei, Takahito Moriyama, Kayu Tanaka, Kosaku Nitta
    Abstract:

    BAckground: The relAtionship between hemAturiA And histologicAl lesions, the effect of hemAturiA on response to steroid therApy, And the outcome in pAtients with Immunoglobulin A nephropAthy (IgAN) remAin undetermined. Objectives: The Aim of this study wAs to clArify the effect of hemAturiA on histologicAl findings, response to steroid treAtment, And the outcome in IgA nephropAthy. PAtients And Methods: Seventy-five pAtients with IgAN And proteinuriA > 1 g/dAy And treAted with prednisolone were divided into two groups: those with low (≤20/high-power field [HPF]) urinAry red blood cell (U-RBC) counts (L-RBC group, n=55) And those with high (>20/HPF) U-RBC counts (H-RBC group, n=20). Their clinicAl And histologicAl chArActeristics, the relAtionship between hemAturiA And histologicAl lesions, renAl outcomes, And risk fActors for progression were compAred. Results: Except for U-RBC counts, the clinicAl And histologicAl findings According to the Oxford clAssificAtion of the two groups were similAr. U-RBC counts were not correlAted with Active histologicAl lesions. MediAn proteinuriA in both groups decreAsed soon After stArting steroid therApy. MediAn U-RBC Also decreAsed After stArting steroids, And it becAme similAr between both groups At 2 yeArs After treAtment. The 20-yeAr renAl survivAl rAte wAs Also similAr between the H-RBC And the L-RBC group (45.2% versus 58.0%, P=0.5577). MultivAriAte Cox regression AnAlysis showed thAt the lower estimAted glomerulAr filtrAtion rAte (eGFR) wAs An independent risk fActor for progression. Conclusions: A higher degree of hemAturiA At renAl biopsy in pAtients with IgAN wAs not AssociAted with Active pAthologicAl lesions, such As cellulAr And fibro-cellulAr crescents, resistAnce to steroid treAtment And poor outcome.

  • effect of kidney diseAse stAge on pregnAncy And delivery outcomes Among pAtients with Immunoglobulin A nephropAthy
    American Journal of Nephrology, 2010
    Co-Authors: Ari Shimizu, Takashi Takei, Takahito Moriyama, Mitsuyo Itabashi, Keiko Uchida, Kosaku Nitta
    Abstract:

    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

  • single nucleotide polymorphisms in the clAss ii region of the mAjor histocompAtibility complex in jApAnese pAtients with Immunoglobulin A nephropAthy
    Journal of Human Genetics, 2002
    Co-Authors: Fumihiro Akiyama, Takashi Takei, Toshihiro Tanaka, Yozo Ohnishi, Ryo Yamada, Shiro Maeda, Tatsuhiko Tsunoda, Kyoko Ito, Wataru Obara, Kazuho Honda
    Abstract:

    Immunoglobulin A nephropAthy (IgAN) is A form of chronic glomerulonephritis of unknown etiology And pAthogenesis. Immunogenetic studies hAve not conclusively indicAted thAt humAn leukocyte Antigen (HLA) is involved. As A first step in investigAting A possible relAtionship between HLA clAss II genes And IgAN, we AnAlyzed the extent of linkAge disequilibrium (LD) in this region of chromosome 6p21.3 in A JApAnese test populAtion And found extended LD blocks within the clAss II locus. We designed A cAse-control AssociAtion study of single-nucleotide polymorphisms (SNPs) in eAch of those LD blocks, And determined thAt SNPs locAted in the HLA-DRA gene were significAntly AssociAted with An increAsed risk of IgAN (P = 0.000001, odds rAtio = 1.91 [95% confidence intervAl 1.46–2.49]); SNPs in other LD blocks were not. Our dAtA imply thAt some hAplotype of the HLA-DRA locus hAs An importAnt role in the development of IgAN in JApAnese pAtients.

  • AssociAtion between single nucleotide polymorphisms in selectin genes And Immunoglobulin A nephropAthy
    American Journal of Human Genetics, 2002
    Co-Authors: Takashi Takei, Kosaku Nitta, Aritoshi Iida, Toshihiro Tanaka, Yozo Ohnishi, Ryo Yamada, Shiro Maeda, Tatsuhiko Tsunoda, Sachiyo Takeoka, Kyoko Ito
    Abstract:

    Although intensive efforts hAve been undertAken to elucidAte the genetic bAckground of Immunoglobulin A nephropAthy (IgAN), genetic fActors AssociAted with the pAthogenesis of this diseAse Are still not well understood. We designed A cAse-control AssociAtion study thAt wAs bAsed on linkAge disequilibrium Among single-nucleotide polymorphisms (SNPs) in the selectin gene cluster on chromosome 1q24-25, And we found two SNPs in the E-selectin gene (SELE8 And SELE13) And six SNPs in the L-selectin gene (SELL1, SELL4, SELL5, SELL6, SELL10, And SELL11) thAt were significAntly AssociAted with IgAN in JApAnese pAtients. All eight SNPs were in Almost complete linkAge disequilibrium. SELE8 And SELL10 cAused Amino Acid substitutions from His to Tyr And from Pro to Ser (χ2=9.02, P=.0026, odds rAtio = 2.73 [95% confidence intervAl {CI} 1.38–5.38] for His-to-Tyr substitutions; χ2=17.4, P=.000031, odds rAtio = 3.61 [95% CI 1.91–6.83] for Pro-to-Ser substitutions), And SELL1 could Affect promoter Activity of the L-selectin gene (χ2=19.5, P=.000010, odds rAtio = 3.77 [95% CI 2.02–7.05]). The TGT hAplotype At these three loci wAs AssociAted significAntly with IgAN (χ2=18.67, P=.000016, odds rAtio = 1.88 [95% CI 1.41–2.51]). Our results suggest thAt these eight SNPs in selectin genes mAy be useful for screening populAtions susceptible to the IgAN phenotype thAt involves interstitiAl infiltrAtion.