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Girerd, S., Girerd, N., Frimat, L., Holdaas, H., Jardine, A. G., Schmieder, R. E., . . . Zannad, F. (2020). Arteriovenous fistula thrombosis is associated with increased all-cause and cardiovascular mortar in haemodialysis patients from the AURORA trial. Clinical Kidney Journal, 13(1), 116-122
Open this publication in new window or tab >>Arteriovenous fistula thrombosis is associated with increased all-cause and cardiovascular mortar in haemodialysis patients from the AURORA trial
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2020 (English)In: Clinical Kidney Journal, ISSN 2048-8505, E-ISSN 2048-8513, Vol. 13, no 1, p. 116-122Article in journal (Refereed) Published
Abstract [en]

Background. The impact of arteriovenous fistula (AVF) or graft (AVG) thrombosis on mortality has been sparsely studied. This study investigated the association between AVF/AVG thrombosis and all-cause and cardiovascular mortality.

Methods. The data from 2439 patients with AVF or AVG undergoing maintenance haemodialysis (HD) included in the A Study to Evaluate the Use of Rosuvastatin in Subjects on Regular Hemodialysis: An Assessment of Survival and Cardiovascular Events trial (AURORA) were analysed using a time-dependent Cox model. The incidence of vascular access (VA) thrombosis was a pre-specified secondary outcome.

Results. During follow-up, 278 AVF and 94 AVG thromboses were documented. VA was restored at 22 +/- 64 days after thrombosis (27 patients had no restoration with subsequent permanent central catheter). In multivariable survival analysis adjusted for potential confounders, the occurrence of AVF/AVG thrombosis was associated with increased early and late allcause mortality, with a more pronounced association with early all-cause mortality {hazard ratio [HR] < 90 days 2.70 [95% confidence interval (CI) 1.83-3.97], P < 0.001; HR > 90 days 1.47 [1.20-1.80], P < 0.001). In addition, the occurrence of AVF thrombosis was significantly associated with higher all-cause mortality, whether VA was restored within 7 days [HR 1.34 (95% CI 1.02-1.75), P = 0.036] or later than 7 days [HR 1.81 (95% CI 1.29-2.53), P = 0.001].

Conclusions. AVF/AVG thrombosis should be considered as a major clinical event since it is strongly associated with increased mortality in patients on maintenance HD, especially in the first 90 days after the event and when access restoration occurs >7 days after thrombosis. Clinicians should pay particular attention to the timing of VA restoration and the management of these patients during this high-risk period. The potential benefit of targeting overall patient risk with more aggressive treatment after AVF/AVG restoration should be further explored.

Keywords
arteriovenous fistula, arteriovenous graft, cardiovascular mortality, chronic haemodialysis, survival, vascular access complication
National Category
Cardiac and Cardiovascular Systems Urology and Nephrology
Identifiers
urn:nbn:se:uu:diva-411001 (URN)10.1093/ckj/sfz048 (DOI)000526719000021 ()32082562 (PubMedID)
Funder
AstraZeneca
Available from: 2020-05-27 Created: 2020-05-27 Last updated: 2020-05-27Bibliographically approved
Fellström, B., Helmersson-Karlqvist, J., Lind, L., Soveri, I., Wu, P.-H., Thulin, M., . . . Larsson, A. (2020). Associations Between Apolipoprotein A1, High-Density Lipoprotein Cholesterol, and Urinary Cytokine Levels in Elderly Males and Females. Journal of Interferon and Cytokine Research, 40(2), 71-74
Open this publication in new window or tab >>Associations Between Apolipoprotein A1, High-Density Lipoprotein Cholesterol, and Urinary Cytokine Levels in Elderly Males and Females
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2020 (English)In: Journal of Interferon and Cytokine Research, ISSN 1079-9907, E-ISSN 1557-7465, Vol. 40, no 2, p. 71-74Article in journal (Refereed) Published
Abstract [en]

There exists a close relationship between cardiovascular diseases and chronic kidney disease. Apolipoprotein A1 and high-density lipoprotein (HDL) cholesterol are widely used as cardiovascular risk markers but they also have anti-inflammatory properties. The aim of this study was to investigate any associations between HDL levels and cytokine levels in urine. We randomly selected 90 urine samples from the Prospective Investigation of the Vasculature in Uppsala Seniors Study (41 males and 49 females). The samples were analyzed with 2 multiplex assays, Multiplex Inflammation I and Cardiovascular II kits (Olink Bioscience, Uppsala, Sweden). We analyzed the correlations between 158 cytokines in urine with apolipoprotein A1, HDL cholesterol, apolipoprotein B, and low-density lipoprotein cholesterol. There were strong correlations for apolipoprotein A1 and HDL cholesterol with individual cytokines. After adjustment for multiplicity testing, there were 33 significant correlations between apolipoprotein A1 and cytokine levels and 14 of these were also significantly correlated with HDL cholesterol. The strongest associations were observed for IL-1 alpha, SPON2, RAGE, PAR-1, TRAIL-R2, IL-4RA, TNFRSF11A, and SCF. A total of 28 out of 33 correlations were negative, indicating a negative relationship between apolipoprotein A1 and urinary cytokines. The study shows a negative correlation between apolipoprotein A1 and HDL cholesterol and urinary cytokine levels. The finding is in agreement with the anti-inflammatory properties of HDL.

Keywords
HDL cholesterol, apolipoprotein A1, cytokines, multiplex assays, urine
National Category
Clinical Laboratory Medicine
Identifiers
urn:nbn:se:uu:diva-394993 (URN)10.1089/jir.2019.0074 (DOI)000510520300001 ()31599692 (PubMedID)
Available from: 2019-10-11 Created: 2019-10-11 Last updated: 2020-03-20Bibliographically approved
Klaasen, R. A., Egeland, E. J., Chan, J., Midtvedt, K., Svensson, M., Boltad, N., . . . Warren, D. J. (2019). A Fully Automated Method for the Determination of Serum Belatacept and Its Application in a Pharmacokinetic Investigation in Renal Transplant Recipients. Therapeutic Drug Monitoring, 41(1), 11-18
Open this publication in new window or tab >>A Fully Automated Method for the Determination of Serum Belatacept and Its Application in a Pharmacokinetic Investigation in Renal Transplant Recipients
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2019 (English)In: Therapeutic Drug Monitoring, ISSN 0163-4356, E-ISSN 1536-3694, Vol. 41, no 1, p. 11-18Article in journal (Refereed) Published
Abstract [en]

Background: Belatacept (Nulojix; Bristol-Myers Squibb, New York, NY) is a biological immunosuppressive drug used for the prophylaxis of acute rejection after renal transplantation. Few studies have described belatacept pharmacokinetics, and the effect of therapeutic drug monitoring has not been investigated. We have developed a drug-capture assay (using drug target) to measure belatacept in serum and applied this assay in a pharmacokinetic study in renal transplant recipients. Methods: CD80 was used to trap belatacept onto streptavidin-coated wells. Captured drug was quantified using Eu3+-labeled protein A and time-resolved fluorescence. The assay was applied in a pilot pharmacokinetic study in renal transplanted patients receiving belatacept infusions. Belatacept serum concentrations were determined at several time points between belatacept infusions. A simple population pharmacokinetic model was developed to visualize measured and predicted belatacept serum concentrations. Results: The assay range was 0.9-30 mg/L with accuracy within 91%-99% and coefficients of variation ranging from 1.2% to 3.6%. Predilution extended the measurement range to 130 mg/L with an accuracy of 90% and coefficients of variation of 3.8%. Samples were stable during storage at 48 degrees C for 15 days and during 2 freeze-thaw cycles. Belatacept concentrations were determined in a total of 203 serum samples collected during 26 infusion intervals from 5 renal transplant recipients. The population pharmacokinetic model visualized both measured and predicted concentrations. Conclusions: We have developed an automated, accurate, and precise assay for the determination of belatacept serum concentrations. The assay was successfully applied in a pharmacokinetic study in renal transplant recipients receiving belatacept infusions.

Place, publisher, year, edition, pages
LIPPINCOTT WILLIAMS & WILKINS, 2019
Keywords
Belatacept, TDM, drug-capture assay, renal transplantation, pharmacokinetics
National Category
Pharmaceutical Sciences
Identifiers
urn:nbn:se:uu:diva-393537 (URN)10.1097/FTD.0000000000000580 (DOI)000480708000002 ()30633722 (PubMedID)
Available from: 2019-09-24 Created: 2019-09-24 Last updated: 2019-09-24Bibliographically approved
de Laval, P., Mobarrez, F., Almquist, T., Vassil, L., Fellström, B. & Soveri, I. (2019). Acute effects of haemodialysis on circulating microparticles. Clinical Kidney Journal, 12(3), 456-462
Open this publication in new window or tab >>Acute effects of haemodialysis on circulating microparticles
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2019 (English)In: Clinical Kidney Journal, ISSN 2048-8505, E-ISSN 2048-8513, Vol. 12, no 3, p. 456-462Article in journal (Refereed) Published
Abstract [en]

Background. Microparticles (MPs) are small cell membrane-derived vesicles regarded as both biomarkers and mediators of biological effects. Elevated levels of MPs have previously been associated with endothelial dysfunction and predict cardiovascular death in patients with end-stage renal disease. The objective of this study was to measure change in MP concentrations in contemporary haemodialysis (HD).

Methods. Blood was sampled from 20 consecutive HD patients before and 1h into the HD session. MPs were measured by flow cytometry and phenotyped based on surface markers.

Results. Concentrations of platelet (CD41(+)) (P = 0.039), endothelial (CD62E(+)) (P = 0.004) andmonocyte-derived MPs (CD14(+)) (P<0.001) significantly increased during HD. Similarly, endothelial-(P = 0.007) and monocyte-derived MPs (P = 0.001) expressing tissue factor (TF) significantly increased as well as MPs expressing Klotho (P = 0.003) and receptor for advanced glycation end products (RAGE) (P = 0.009). Furthermore, MPs expressing platelet activationmarkers P-selectin (P = 0.009) and CD40L (P = 0.045) also significantly increased. The increase of endothelial (P = 0.034), monocyte (P = 0.014) and RAGE(+) MPs (P = 0.032) as well as TF+ platelet-derived MPs (P = 0.043) was significantly higher in patients treated with low-flux compared with high-flux dialysers.

Conclusion. Dialysis triggers release of MPs of various origins with marked differences between high-flux and low-flux dialysers. The MPs carry surface molecules that could possibly influence coagulation, inflammation, oxidative stress and endothelial dysfunction. The clinical impact of these findings remains to be established in future studies.

Keywords
chronic kidney disease, haemodialysis, Klotho, microparticles, RAGE
National Category
Hematology Urology and Nephrology
Identifiers
urn:nbn:se:uu:diva-397125 (URN)10.1093/ckj/sfy109 (DOI)000493450200022 ()31198549 (PubMedID)
Available from: 2019-11-29 Created: 2019-11-29 Last updated: 2019-11-29Bibliographically approved
Groopman, E. E., Marasa, M., Cameron-Christie, S., Petrovski, S., Aggarwal, V. S., Milo-Rasouly, H., . . . Gharavi, A. G. (2019). Diagnostic Utility of Exome Sequencing for Kidney Disease. New England Journal of Medicine, 380(2), 142-151
Open this publication in new window or tab >>Diagnostic Utility of Exome Sequencing for Kidney Disease
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2019 (English)In: New England Journal of Medicine, ISSN 0028-4793, E-ISSN 1533-4406, Vol. 380, no 2, p. 142-151Article in journal (Refereed) Published
Abstract [en]

BACKGROUND Exome sequencing is emerging as a first-line diagnostic method in some clinical disciplines, but its usefulness has yet to be examined for most constitutional disorders in adults, including chronic kidney disease, which affects more than 1 in 10 persons globally.

METHODS We conducted exome sequencing and diagnostic analysis in two cohorts totaling 3315 patients with chronic kidney disease. We assessed the diagnostic yield and, among the patients for whom detailed clinical data were available, the clinical implications of diagnostic and other medically relevant findings.

RESULTS In all, 3037 patients (91.6%) were over 21 years of age, and 1179 (35.6%) were of self-identified non-European ancestry. We detected diagnostic variants in 307 of the 3315 patients (9.3%), encompassing 66 different monogenic disorders. Of the disorders detected, 39 (59%) were found in only a single patient. Diagnostic variants were detected across all clinically defined categories, including congenital or cystic renal disease (127 of 531 patients [23.9%]) and nephropathy of unknown origin (48 of 281 patients [17.1%]). Of the 2187 patients assessed, 34 (1.6%) had genetic findings for medically actionable disorders that, although unrelated to their nephropathy, would also lead to subspecialty referral and inform renal management.

CONCLUSIONS Exome sequencing in a combined cohort of more than 3000 patients with chronic kidney disease yielded a genetic diagnosis in just under 10% of cases.

National Category
Urology and Nephrology
Identifiers
urn:nbn:se:uu:diva-375897 (URN)10.1056/NEJMoa1806891 (DOI)000455310300008 ()30586318 (PubMedID)
Funder
AstraZeneca
Available from: 2019-02-04 Created: 2019-02-04 Last updated: 2019-02-04Bibliographically approved
Barbour, S. J., Coppo, R., Zhang, H., Liu, Z.-H., Suzuki, Y., Matsuzaki, K., . . . Trimarchi, H. (2019). Evaluating a New International Risk-Prediction Tool in IgA Nephropathy. Paper presented at ISN World Congress of Nephrology, APR 13, 2019, Melbourne, AUSTRALIA. JAMA Internal Medicine, 179(7), 942-952
Open this publication in new window or tab >>Evaluating a New International Risk-Prediction Tool in IgA Nephropathy
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2019 (English)In: JAMA Internal Medicine, ISSN 2168-6106, E-ISSN 2168-6114, Vol. 179, no 7, p. 942-952Article in journal (Refereed) Published
Abstract [en]

Importance  Although IgA nephropathy (IgAN) is the most common glomerulonephritis in the world, there is no validated tool to predict disease progression. This limits patient-specific risk stratification and treatment decisions, clinical trial recruitment, and biomarker validation.

Objective  To derive and externally validate a prediction model for disease progression in IgAN that can be applied at the time of kidney biopsy in multiple ethnic groups worldwide.

Design, Setting, and Participants  We derived and externally validated a prediction model using clinical and histologic risk factors that are readily available in clinical practice. Large, multi-ethnic cohorts of adults with biopsy-proven IgAN were included from Europe, North America, China, and Japan.

Main Outcomes and Measures  Cox proportional hazards models were used to analyze the risk of a 50% decline in estimated glomerular filtration rate (eGFR) or end-stage kidney disease, and were evaluated using the R2D measure, Akaike information criterion (AIC), C statistic, continuous net reclassification improvement (NRI), integrated discrimination improvement (IDI), and calibration plots.

Results  The study included 3927 patients; mean age, 35.4 (interquartile range, 28.0-45.4) years; and 2173 (55.3%) were men. The following prediction models were created in a derivation cohort of 2781 patients: a clinical model that included eGFR, blood pressure, and proteinuria at biopsy; and 2 full models that also contained the MEST histologic score, age, medication use, and either racial/ethnic characteristics (white, Japanese, or Chinese) or no racial/ethnic characteristics, to allow application in other ethnic groups. Compared with the clinical model, the full models with and without race/ethnicity had better R2D (26.3% and 25.3%, respectively, vs 20.3%) and AIC (6338 and 6379, respectively, vs 6485), significant increases in C statistic from 0.78 to 0.82 and 0.81, respectively (ΔC, 0.04; 95% CI, 0.03-0.04 and ΔC, 0.03; 95% CI, 0.02-0.03, respectively), and significant improvement in reclassification as assessed by the NRI (0.18; 95% CI, 0.07-0.29 and 0.51; 95% CI, 0.39-0.62, respectively) and IDI (0.07; 95% CI, 0.06-0.08 and 0.06; 95% CI, 0.05-0.06, respectively). External validation was performed in a cohort of 1146 patients. For both full models, the C statistics (0.82; 95% CI, 0.81-0.83 with race/ethnicity; 0.81; 95% CI, 0.80-0.82 without race/ethnicity) and R2D (both 35.3%) were similar or better than in the validation cohort, with excellent calibration.

Conclusions and Relevance  In this study, the 2 full prediction models were shown to be accurate and validated methods for predicting disease progression and patient risk stratification in IgAN in multi-ethnic cohorts, with additional applications to clinical trial design and biomarker research.

National Category
Urology and Nephrology
Identifiers
urn:nbn:se:uu:diva-393135 (URN)10.1001/jamainternmed.2019.0600 (DOI)000477893300017 ()30980653 (PubMedID)
Conference
ISN World Congress of Nephrology, APR 13, 2019, Melbourne, AUSTRALIA
Available from: 2019-09-24 Created: 2019-09-24 Last updated: 2019-09-24Bibliographically approved
Cameron-Christie, S., Wolock, C. J., Groopman, E., Petrovski, S., Kamalakaran, S., Povysil, G., . . . Gharavi, A. G. (2019). Exome-Based Rare-Variant Analyses in CKD. Journal of the American Society of Nephrology, 30(6), 1109-1122
Open this publication in new window or tab >>Exome-Based Rare-Variant Analyses in CKD
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2019 (English)In: Journal of the American Society of Nephrology, ISSN 1046-6673, E-ISSN 1533-3450, Vol. 30, no 6, p. 1109-1122Article in journal (Refereed) Published
Abstract [en]

Background Studies have identified many common genetic associations that influence renal function and all-cause CKD, but these explain only a small fraction of variance in these traits. The contribution of rare variants has not been systematically examined. Methods We performed exome sequencing of 3150 individuals, who collectively encompassed diverse CKD subtypes, and 9563 controls. To detect causal genes and evaluate the contribution of rare variants we used collapsing analysis, in which we compared the proportion of cases and controls carrying rare variants per gene. Results The analyses captured five established monogenic causes of CKD: variants in PKD1, PKD2, and COL4A5 achieved study-wide significance, and we observed suggestive case enrichment for COL4A4 and COL4A3. Beyond known disease-associated genes, collapsing analyses incorporating regional variant intolerance identified suggestive dominant signals in CPT2 and several other candidate genes. Biallelic mutations in CPT2 cause carnitine palmitoyltransferase II deficiency, sometimes associated with rhabdomyolysis and acute renal injury. Genetic modifier analysis among cases with APOL1 risk genotypes identified a suggestive signal in AHDC1, implicated in Xia-Gibbs syndrome, which involves intellectual disability and other features. On the basis of the observed distribution of rare variants, we estimate that a two-to three-fold larger cohort would provide 80% power to implicate new genes for all-cause CKD. Conclusions This study demonstrates that rare-variant collapsing analyses can validate known genes and identify candidate genes and modifiers for kidney disease. In so doing, these findings provide a motivation for larger-scale investigation of rare-variant risk contributions across major clinical CKD categories.

Place, publisher, year, edition, pages
AMER SOC NEPHROLOGY, 2019
National Category
Urology and Nephrology
Identifiers
urn:nbn:se:uu:diva-390637 (URN)10.1681/ASN.2018090909 (DOI)000474779900019 ()31085678 (PubMedID)
Funder
AstraZeneca
Available from: 2019-08-21 Created: 2019-08-21 Last updated: 2019-08-21Bibliographically approved
Pihlstrøm, H. K., Mjøen, G., Mucha, S., Franke, A., Jardine, A., Fellström, B., . . . Melum, E. (2019). Genetic markers associated with long term cardiovascular outcome in kidney transplant recipients. American Journal of Transplantation, 19(5), 1444-1451
Open this publication in new window or tab >>Genetic markers associated with long term cardiovascular outcome in kidney transplant recipients
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2019 (English)In: American Journal of Transplantation, ISSN 1600-6135, E-ISSN 1600-6143, Vol. 19, no 5, p. 1444-1451Article in journal (Refereed) Published
Abstract [en]

There is a clear genetic contribution to the risk of cardiovascular diseases, and a composite genetic risk score (GRS) based on 27 single nucleotide polymorphisms (SNPs) was reported to predict risk of cardiovascular events in the general population. We aimed to evaluate this risk score in renal transplant recipients, a population with heightened cardiovascular risk, with a yet unknown genetic contribution. This article is protected by copyright. All rights reserved.

Place, publisher, year, edition, pages
John Wiley & Sons, 2019
Keywords
biomarker, clinical research/practice, coronary artery disease, epidemiology, genetics, kidney transplantation/nephrology, risk assessment/risk stratification, translational research/science
National Category
Cardiac and Cardiovascular Systems Urology and Nephrology Surgery
Identifiers
urn:nbn:se:uu:diva-368933 (URN)10.1111/ajt.15191 (DOI)000471342300022 ()30457209 (PubMedID)
Available from: 2018-12-10 Created: 2018-12-10 Last updated: 2019-08-06Bibliographically approved
Fellström, B., Holmdahl, J., Sundvall, N., Cockburn, E., Kilany, S. & Wennberg, L. (2018). Adherence of Renal Transplant Recipients to Once-daily, Prolonged-Release and Twice-daily, Immediate-release Tacrolimus-based Regimens in a Real-life Setting in Sweden. Transplantation Proceedings, 50(10), 3275-3282
Open this publication in new window or tab >>Adherence of Renal Transplant Recipients to Once-daily, Prolonged-Release and Twice-daily, Immediate-release Tacrolimus-based Regimens in a Real-life Setting in Sweden
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2018 (English)In: Transplantation Proceedings, ISSN 0041-1345, E-ISSN 1873-2623, Vol. 50, no 10, p. 3275-3282Article in journal (Refereed) Published
Abstract [en]

Background. In this study we investigated medication adherence of kidney transplant patients (KTPs) to an immediate-release tacrolimus (IR-T) regimen and, after conversion, to a prolonged-release tacrolimus (PR-T) regimen in routine clinical practice. Methods. This was a non-interventional, observational, multicenter Swedish study. We included adult KTPs with stable graft function, remaining on IR-T or converting from IR-T to PR-T. Data were collected at baseline, and months 3, 6, and 12 post-baseline. The primary endpoint was adherence using the Basel Assessment of Adherence to Immunosuppressive Medication Scale (BAASIS). Secondary assessments included tacrolimus dose and trough levels, clinical laboratory parameters (eg, estimated glomerular filtration rate), and adverse drug reactions (ADRs). Results. Overall, data from 233 KTPs were analyzed (PR-T, n = 175; IR-T, n = 58). Mean change in PR-T dose from baseline (4.8 mg/d) to month 12 was -0.2 mg/d, and for IR-T (4.2 mg/d) was-0.4 mg/d; tacrolimus trough levels remained similar. Overall adherence was similar between baseline and month 12 in both groups (PR-T: 54.4% vs 57.0%, respectively; IR-T: 65.5% vs 69.4%); timing adherence followed a similar pattern. The probability of taking adherence improved between baseline and month 12 (odds ratio, 1.97; P =.0092) in the PR-T group only. Mean BAASIS visual analog scale score at baseline was 94.3 11.1% (PR-T) and 95.3 7.6% (IR-T), and >95% at subsequent visits. Laboratory parameters remained stable. Eight (4.6%) patients receiving PR-T (none receiving IR-T) had ADRs considered probably/possibly treatment-related. Conclusion. Disparity existed between high, patient-perceived and low, actual adherence. Overall adherence to the immunosuppressive regimen (measured by BAASIS) did not improve significantly over 12 months in stable KTPs converting to PR-T or remaining on IR-T; renal function remained stable.

National Category
Surgery
Identifiers
urn:nbn:se:uu:diva-374125 (URN)10.1016/j.transproceed.2018.06.027 (DOI)000454972000058 ()30577197 (PubMedID)
Available from: 2019-01-23 Created: 2019-01-23 Last updated: 2019-01-23Bibliographically approved
Coppo, R., D'Arrigo, G., Tripepi, G., Russo, M. L., Roberts, I. S., Bellur, S., . . . Zoccali, C. (2018). Is there long-term value of pathology scoring in immunoglobulin A nephropathy?: A validation study of the Oxford Classification for IgA Nephropathy (VALIGA) update. Nephrology, Dialysis and Transplantation
Open this publication in new window or tab >>Is there long-term value of pathology scoring in immunoglobulin A nephropathy?: A validation study of the Oxford Classification for IgA Nephropathy (VALIGA) update
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2018 (English)In: Nephrology, Dialysis and Transplantation, ISSN 0931-0509, E-ISSN 1460-2385Article in journal (Refereed) Epub ahead of print
Abstract [en]

Background: It is unknown whether renal pathology lesions in immunoglobulin A nephropathy (IgAN) correlate with renal outcomes over decades of follow-up.

Methods: In 1130 patients of the original Validation Study of the Oxford Classification for IgA Nephropathy (VALIGA) cohort, we studied the relationship between the MEST score (mesangial hypercellularity, M; endocapillary hypercellularity, E; segmental glomerulosclerosis, S; tubular atrophy/interstitial fibrosis, T), crescents (C) and other histological lesions with both a combined renal endpoint [50% estimated glomerular filtration rate (eGFR) loss or kidney failure] and the rate of eGFR decline over a follow-up period extending to 35 years [median 7 years (interquartile range 4.1-10.8)].

Results: In this extended analysis, M1, S1 and T1-T2 lesions as well as the whole MEST score were independently related with the combined endpoint (P < 0.01), and there was no effect modification by age for these associations, suggesting that they may be valid in children and in adults as well. Only T lesions were associated with the rate of eGFR loss in the whole cohort, whereas C showed this association only in patients not treated with immunosuppression. In separate prognostic analyses, the whole set of pathology lesions provided a gain in discrimination power over the clinical variables alone, which was similar at 5 years (+2.0%) and for the whole follow-up (+1.8%). A similar benefit was observed for risk reclassification analyses (+2.7% and +2.4%).

Conclusion: Long-term follow-up analyses of the VALIGA cohort showed that the independent relationship between kidney biopsy findings and the risk of progression towards kidney failure in IgAN remains unchanged across all age groups and decades after the renal biopsy.

National Category
Nursing Cardiac and Cardiovascular Systems
Identifiers
urn:nbn:se:uu:diva-368934 (URN)10.1093/ndt/gfy302 (DOI)30418652 (PubMedID)
Available from: 2018-12-10 Created: 2018-12-10 Last updated: 2019-02-06Bibliographically approved
Organisations
Identifiers
ORCID iD: ORCID iD iconorcid.org/0000-0001-5409-9729

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