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1. Application of the International IgA Nephropathy Prediction Tool one or two years post-biopsy

Author

Barbour, Sean J., Coppo, Rosanna, Zhang, Hong, Liu, Zhi-Hong, Suzuki, Yusuke, Matsuzaki, Keiichi, Er, Lee, Reich, Heather N., Barratt, Jonathan, Cattran, Daniel C., Russo, M.L., Troyanov, S., Cook, H.T., Roberts, I., Tesar, V., Maixnerova, D., Lundberg, S., Gesualdo, L., Emma, F., Fuiano, L., Beltrame, G., Rollino, C., Amore, A., Camilla, R., Peruzzi, L., Praga, M., Feriozzi, S., Polci, R., Segoloni, G., Colla, L., Pani, A., Piras, D., Angioi, A., Cancarini, G., Ravera, S., Durlik, M., Moggia, E., Ballarin, J., Di Giulio, S., Pugliese, F., Serriello, I., Caliskan, Y., Sever, M., Kilicaslan, I., Locatelli, F., Del Vecchio, L., Wetzels, J.F.M., Peters, H., Berg, U., Carvalho, F., da Costa Ferreira, A.C., Maggio, M., Wiecek, A., Ots-Rosenberg, M., Magistroni, R., Topaloglu, R., Bilginer, Y., D’Amico, M., Stangou, M., Giacchino, F., Goumenos, D., Papachristou, E., Galesic, K., Geddes, C., Siamopoulos, K., Balafa, O., Galliani, M., Stratta, P., Quaglia, M., Bergia, R., Cravero, R., Salvadori, M., Cirami, L., Fellstrom, B., Smerud, H. Kloster, Ferrario, F., Stellato, T., Egido, J., Martin, C., Floege, J., Eitner, F., Lupo, A., Bernich, P., Menè, P., Morosetti, M., van Kooten, C., Rabelink, T., Reinders, M.E.J., Boria Grinyo, J.M., Cusinato, S., Benozzi, L., Savoldi, S., Licata, C., Mizerska-Wasiak, M., Martina, G., Messuerotti, A., Dal Canton, A., Esposito, C., Migotto, C., Triolo, G., Mariano, F., Pozzi, C., Boero, R., Bellur, S., Mazzucco, G., Giannakakis, C., Honsova, E., Sundelin, B., Di Palma, A.M., Ferrario, F., Gutiérrez, E., Asunis, A.M., Barratt, J., Tardanico, R., Perkowska-Ptasinska, A., Terroba, J. Arce, Fortunato, M., Pantzaki, A., Ozluk, Y., Steenbergen, E., Soderberg, M., Riispere, Z., Furci, L., Orhan, D., Kipgen, D., Casartelli, D., Ljubanovic, D. Galesic, Gakiopoulou, H., Bertoni, E., Cannata Ortiz, P., Karkoszka, H., Groene, H.J., Stoppacciaro, A., Bajema, I., Bruijn, J., Fulladosa Oliveras, X., Maldyk, J., Ioachim, E., Bavbek, N., Cook, T., Troyanov, S., Alpers, C., Amore, A., Barratt, J., Berthoux, F., Bonsib, S., Bruijn, J., D’Agati, V., D’Amico, G., Emancipator, S., Emmal, F., Ferrario, F., Fervenza, F., Florquin, S., Fogo, A., Geddes, C., Groene, H., Haas, M., Hill, P., Hogg, R., Hsu, S., Hunley, T., Hladunewich, M., Jennette, C., Joh, K., Julian, B., Kawamura, T., Lai, F., Leung, C., Li, L., Li, P., Liu, Z., Massat, A., Mackinnon, B., Mezzano, S., Schena, F., Tomino, Y., Walker, P., Wang, H., Weening, J., Yoshikawa, N., Zeng, C.-H., Shi, S., Nogi, C., Suzuki, H., Koike, K., Hirano, K., Kawamura, T., Yokoo, T., Hanai, M., Fukami, K., Takahashi, K., Yuzawa, Y., Niwa, M., Yasuda, Y., Maruyama, S., Ichikawa, D., Suzuki, T., Shirai, S., Fukuda, A., Fujimoto, S., and Trimarchi, H.

Abstract

The International IgA Nephropathy (IgAN) Prediction Tool is the preferred method in the 2021 KDIGO guidelines to predict, at the time of kidney biopsy, the risk of a 50% drop in estimated glomerular filtration rate or kidney failure. However, it is not known if the Prediction Tool can be accurately applied after a period of observation post-biopsy. Using an international multi-ethnic derivation cohort of 2,507 adults with IgAN, we updated the Prediction Tool for use one year after biopsy, and externally validated this in a cohort of 722 adults. The original Prediction Tool applied at one-year without modification had a coefficient of variation (R2) of 55% and 54% and four-year concordance (C statistic) of 0.82 but poor calibration with under-prediction of risk (integrated calibration index (ICI) 1.54 and 2.11, with and without race, respectively). Our updated Prediction Tool had a better model fit with higher R2(61% and 60%), significant increase in four-year C-statistic (0.87 and 0.86) and better four-year calibration with lower ICI (0.75 and 0.35). On external validation, the updated Prediction Tool had similar R2(60% and 58%) and four-year C-statistics (both 0.85) compared to the derivation analysis, with excellent four-year calibration (ICI 0.62 and 0.56). This updated Prediction Tool had similar prediction performance when used two years after biopsy. Thus, the original Prediction Tool should be used only at the time of biopsy whereas our updated Prediction Tool can be used for risk stratification one or two years post-biopsy.

Published
2022
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2. Development and testing of an artificial intelligence tool for predicting end-stage kidney disease in patients with immunoglobulin A nephropathy

Author

Schena, Francesco Paolo, Anelli, Vito Walter, Trotta, Joseph, Di Noia, Tommaso, Manno, Carlo, Tripepi, Giovanni, D’Arrigo, Graziella, Chesnaye, Nicholas C., Russo, Maria Luisa, Stangou, Maria, Papagianni, Aikaterini, Zoccali, Carmine, Tesar, Vladimir, Coppo, Rosanna, Tesar, V., Maixnerova, D., Lundberg, S., Gesualdo, L., Emma, F., Fuiano, L., Beltrame, G., Rollino, C., Coppo, R., Amore, A., Camilla, R., Peruzzi, L., Praga, M., Feriozzi, S., Polci, R., Segoloni, G., Colla, L., Pani, A., Angioi, A., Piras, L., Feehally, J., Cancarini, G., Ravera, S., Durlik, M., Moggia, E., Ballarin, J., Di Giulio, S., Pugliese, F., Serriello, I., Caliskan, Y., Sever, M., Kilicaslan, I., Locatelli, F., Del Vecchio, L., Wetzels, J.F.M., Peters, H., Berg, U., Carvalho, F., da Costa Ferreira, A.C., Maggio, M., Wiecek, A., Ots-Rosenberg, M., Magistroni, R., Topaloglu, R., Bilginer, Y., D’Amico, M., Stangou, M., Giacchino, F., Goumenos, D., Papasotiriou, M., Galesic, K., Toric, L., Geddes, C., Siamopoulos, K., Balafa, O., Galliani, M., Stratta, P., Quaglia, M., Bergia, R., Cravero, R., Salvadori, M., Cirami, L., Fellstrom, B., Smerud, H. Kloster, Ferrario, F., Stellato, T., Egido, J., Martin, C., Floege, J., Eitner, F., Rauen, T., Lupo, A., Bernich, P., Menè, P., Morosetti, M., van Kooten, C., Rabelink, T., Reinders, M.E.J., Grinyo, J.M. Boria, Cusinato, S., Benozzi, L., Savoldi, S., Licata, C., Mizerska-Wasiak, M., Roszkowska-Blaim, M., Martina, G., Messuerotti, A., Canton, A. Dal, Esposito, C., Migotto, C., Triolo, G., Mariano, F., Pozzi, C., Boero, R., Mazzucco, Giannakakis, C., Honsova, E., Sundelin, B., Di Palma, A.M., Ferrario, F., Gutiérrez, E., Asunis, A.M., Barratt, J., Tardanico, R., Perkowska-Ptasinska, A., Terroba, J. Arce, Fortunato, M., Pantzaki, A., Ozluk, Y., Steenbergen, E., Soderberg, M., Riispere, Z., Furci, L., Orhan, D., Kipgen, D., Casartelli, D., GalesicLjubanovic, D., Gakiopoulou, H., Bertoni, E., Ortiz, P. Cannata, Karkoszka, H., Groene, H.J., Stoppacciaro, A., Bajema, I., Bruijn, J., FulladosaOliveras, X., Maldyk, J., Ioachim, E., Abbrescia, Daniela, Kouri, Nikoleta, Stangou, Maria, Papagianni, Aikaterini, Scolari, Francesco, Delbarba, Elisa, Bonomini, Mario, Piscitani, Luca, Stallone, Giovanni, Infante, Barbara, Godeas, Giulia, Madio, Desiree, Biancone, Luigi, Campagna, Marco, Zaza, Gianluigi, Squarzoni, Isabella, and Cangemi, Concetta

Abstract

We have developed an artificial neural network prediction model for end-stage kidney disease (ESKD) in patients with primary immunoglobulin A nephropathy (IgAN) using a retrospective cohort of 948 patients with IgAN. Our tool is based on a two-step procedure of a classifier model that predicts ESKD, and a regression model that predicts development of ESKD over time. The classifier model showed a performance value of 0.82 (area under the receiver operating characteristic curve) in patients with a follow-up of five years, which improved to 0.89 at the ten-year follow-up. Both models had a higher recall rate, which indicated the practicality of the tool. The regression model showed a mean absolute error of 1.78 years and a root mean square error of 2.15 years. Testing in an independent cohort of 167patients with IgAN found successful results for 91% of the patients. Comparison of our system with other mathematical models showed the highest discriminant Harrell C index at five- and ten-years follow-up (81% and 86%, respectively), paralleling the lowest Akaike information criterion values (355.01 and 269.56, respectively). Moreover, our system was the best calibrated model indicating that the predicted and observed outcome probabilities did not significantly differ. Finally, the dynamic discrimination indexes of our artificial neural network, expressed as the weighted average of time-dependent areas under the curve calculated at one and two years, were 0.80 and 0.79, respectively. Similar results were observed over a 25-year follow-up period. Thus, our tool identified individuals who were at a high risk of developing ESKD due to IgAN and predicted the time-to-event endpoint. Accurate prediction is an important step toward introduction of a therapeutic strategy for improving clinical outcomes.

Published
2021
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3. Improving treatment decisions using personalized risk assessment from the International IgA Nephropathy Prediction Tool

Author

Barbour, Sean J., Canney, Mark, Coppo, Rosanna, Zhang, Hong, Liu, Zhi-Hong, Suzuki, Yusuke, Matsuzaki, Keiichi, Katafuchi, Ritsuko, Induruwage, Dilshani, Er, Lee, Reich, Heather N., Feehally, John, Barratt, Jonathan, Cattran, Daniel C., Russo, M.L., Troyanov, S., Cook, H.T., Roberts, I., Tesar, V., Maixnerova, D., Lundberg, S., Gesualdo, L., Emma, F., Fuiano, L., Beltrame, G., Rollino, C., Amore, A., Camilla, R., Peruzzi, L., Praga, M., Feriozzi, S., Polci, R., Segoloni, G., Colla, L., Pani, A., Piras, D., Angioi, A., Cancarini, G., Ravera, S., Durlik, M., Moggia, E., Ballarin, J., Di Giulio, S., Pugliese, F., Serriello, I., Caliskan, Y., Sever, M., Kilicaslan, I., Locatelli, F., Del Vecchio, L., Wetzels, J.F.M., Peters, H., Berg, U., Carvalho, F., da Costa Ferreira, A.C., Maggio, M., Wiecek, A., Ots-Rosenberg, M., Magistroni, R., Topaloglu, R., Bilginer, Y., D’Amico, M., Stangou, M., Giacchino, F., Goumenos, D., Kalliakmani, P., Gerolymos, M., Galesic, K., Geddes, C., Siamopoulos, K., Balafa, O., Galliani, M., Stratta, P., Quaglia, M., Bergia, R., Cravero, R., Salvadori, M., Cirami, L., Fellstrom, B., Kloster Smerud, H., Ferrario, F., Stellato, T., Egido, J., Martin, C., Floege, J., Eitner, F., Lupo, A., Bernich, P., Menè, P., Morosetti, M., van Kooten, C., Rabelink, T., Reinders, M.E.J., Boria Grinyo, J.M., Cusinato, S., Benozzi, L., Savoldi, S., Licata, C., Mizerska-Wasiak, M., Martina, G., Messuerotti, A., Dal Canton, A., Esposito, C., Migotto, C., Triolo, G., Mariano, F., Pozzi, C., Boero, R., Bellur, S., Mazzucco, G., Giannakakis, C., Honsova, E., Sundelin, B., Di Palma, A.M., Ferrario, F., Gutiérrez, E., Asunis, A.M., Barratt, J., Tardanico, R., Perkowska-Ptasinska, A., Arce Terroba, J., Fortunato, M., Pantzaki, A., Ozluk, Y., Steenbergen, E., Soderberg, M., Riispere, Z., Furci, L., Orhan, D., Kipgen, D., Casartelli, D., Galesic Ljubanovic, D., Gakiopoulou, H., Bertoni, E., Cannata Ortiz, P., Karkoszka, H., Groene, H.J., Stoppacciaro, A., Bajema, I., Bruijn, J., Fulladosa Oliveras, X., Maldyk, J., Ioachim, E., Bavbek, N., Cook, T., Troyanov, S., Alpers, C., Amore, A., Barratt, J., Berthoux, F., Bonsib, S., Bruijn, J., D’Agati, V., D’Amico, G., Emancipator, S., Emmal, F., Ferrario, F., Fervenza, F., Florquin, S., Fogo, A., Geddes, C., Groene, H., Haas, M., Hill, P., Hogg, R., Hsu, S., Hunley, T., Hladunewich, M., Jennette, C., Joh, K., Julian, B., Kawamura, T., Lai, F., Leung, C., Li, L., Li, P., Liu, Z., Massat, A., Mackinnon, B., Mezzano, S., Schena, F., Tomino, Y., Walker, P., Wang, H., Weening, J., Yoshikawa N, N., Zeng, C.-H., Shi, S., Nogi, C., Suzuki, H., Koike, K., Hirano, K., Kawamura, T., Yokoo, T., Hanai, M., Fukami, K., Takahashi, K., Yuzawa, Y., Niwa, M., Yasuda, Y., Maruyama, S., Ichikawa, D., Suzuki, T., Shirai, S., Fukuda, A., Fujimoto, S., and Trimarchi, H.

Abstract

Immunosuppression in IgA nephropathy (IgAN) should be reserved for patients at high-risk of disease progression, which KDIGO guidelines determine based solely on proteinuria 1g or more/day. To investigate if treatment decisions can be more accurately accomplished using individualized risk from the International IgAN Prediction Tool, we simulated allocation of a hypothetical immunosuppression therapy in an international cohort of adults with IgAN. Two decision rules for treatment were applied based on proteinuria of 1g or more/day or predicted risk from the Prediction Tool above a threshold probability. An appropriate decision was defined as immunosuppression allocated to patients experiencing the primary outcome (50% decline in eGFR or ESKD) and withheld otherwise. The net benefit and net reduction in treatment are the proportion of patients appropriately allocated to receive or withhold immunosuppression, adjusted for the harm from inappropriate decisions, calculated for all threshold probabilities from 0-100%. Of 3299 patients followed for 5.1 years, 522 (15.8%) experienced the primary outcome. Treatment allocation based solely on proteinuria of 1g or more/day had a negative net benefit (was harmful) because immunosuppression was increasingly allocated to patients without progressive disease. Compared to using proteinuria, treatment allocation using the Prediction Tool had a larger net benefit up to 23.4% (95% confidence interval 21.5-25.2%) and a larger net reduction in treatment up to 35.1% (32.3-37.8%). Thus, allocation of immunosuppression to high-risk patients with IgAN can be substantially improved using the Prediction Tool compared to using proteinuria.

Published
2020
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4. Evidence from the large VALIGA cohort validates the subclassification of focal segmental glomerulosclerosis in IgA nephropathy

Author

Bellur, Shubha S., Troyanov, Stéphan, Vorobyeva, Olga, Coppo, Rosanna, Roberts, Ian S.D., Coppo, R., Feehaly, J., Troyanov, S., Cattran, D.C., Cook, H.T., Roberts, I., Radcliffe, John, Russo, M.L., Tesar, V., Maixnerova, D., Lundberg, S., Gesualdo, L., Emma, F., Fuiano, L., Beltrame, G., Rollino, C., Amore, A., Camilla, R., Peruzzi, L., Praga, M., Feriozzi, S., Polci, R., Segoloni, G., Colla, L., Pani, A., Piras, D., Angioi, A., Cancarini, G., Ravera, S., Durlik, M., Moggia, E., Ballarin, J., Di Giulio, S., Pugliese, F., Serriello, I., Caliskan, Y., Sever, M., Kilicaslan, I., Locatelli, F., Del Vecchio, L., Wetzels, J.F.M., Peters, H., Berg, U., Carvalho, F., da Costa Ferreira, A.C., Maggio, M., Wiecek, A., Ots-Rosenberg, M., Magistroni, R., Topaloglu, R., Bilginer, Y., D’Amico, M., Papagianni, K., Stangou, M., Giacchino, F., Goumenos, D., Papasotirious, M., Kalliakmani, P., Gerolymos, M., Galesic, K., Toric, L., Geddes, C., Siamopoulos, K., Balafa, O., Galliani, M., Stratta, P., Quaglia, M., Bergia, R., Cravero, R., Salvadori, M., Cirami, L., Fellstrom, B., Kloster Smerud, H., Ferrario, F., Stellato, T., Egido, J., Martin, C., Floege, J., Eitner, F., Lupo, A., Bernich, P., Menè, P., Morosetti, M., van Kooten, C., Rabelink, T., Reinders, M.E.J., Boria Grinyo, J.M., Cusinato, S., Benozzi, L., Savoldi, S., Licata, C., Mizerska-Wasiak, M., Roszkowska-Blaim, M., Durlik, M., Hryszko, T., Klinger, M., Kamińska, D., Krajewska, M., Martina, G., Messuerotti, A., Dal Canton, A., Esposito, C., Migotto, C., Triolo, G., Mariano, F., Pozzi, C., Boero, R., Cambier, A., Bellur, S., Mazzucco, G., Giannakakis, C., Honsova, E., Sundelin, B., Di Palma, A.M., Ferrario, F., Diomedi-Casadei, F., Gutiérrez, E., Asunis, A.M., Barratt, J., Tardanico, R., Perkowska-Ptasinska, A., Arce Terroba, J., Fortunato, M., Pantzaki, A., Ozluk, Y., Steenbergen, E., Soderberg, M., Riispere, Z., Furci, L., Orhan, D., Kipgen, D., Casartelli, D., Galesic Ljubanovic, D., Gakiopoulou, H., Bertoni, E., Cannata Ortiz, P., Karkoszka, H., Groene, H.J., Stoppacciaro, A., Bajema, I., Bruijn, J., Fulladosa Oliveras, X., Maldyk, J., Ioachim, E., and Royal, V.

Abstract

Evidence from the Oxford IgA nephropathy (IgAN) cohort supports the clinical value of subclassifying focal segmental glomerulosclerosis lesions (S1). Using the larger Validation in IgA (VALIGA) study cohort, we investigated the association between podocytopathic changes and higher proteinuria, kidney outcome and response to immunosuppressive therapy. All biopsies were evaluated for glomeruli with segmental capillary occlusion by matrix (“not otherwise specified”, NOS lesion), simple capsular adhesion without capillary occlusion (Adh), tip lesions, and podocyte hypertrophy (PH). S1 required a NOS lesion and/or Adh. A Chi-Squared Automatic Interaction Detection method was used to identify subgroups of FSGS lesions associated with distinctive proteinuria at biopsy and assessed survival from a combined event (kidney failure or 50% decline in estimated glomerular filtration rate). Finally, we evaluated within each subgroup if immunosuppression was associated with a favorable outcome using propensity analysis. In 1147 patients, S1 was found in 70% of biopsies. Subclassification found NOS lesions in 44%, Adh in 59%, PH in 13%, and tip lesions in 3%, with much overlap. Four subgroups were identified with progressively higher proteinuria: from lowest, S1 without NOS, S1 with NOS but without Adh/PH, to highest, S1 with NOS and Adh but without PH, and S1 with NOS and PH. These four subgroups showed progressively worse kidney survival. Immunosuppression was associated with a better outcome only in the two highest proteinuria subgroups. Propensity analysis in these two groups, adjusted for clinical and pathological findings, found a significant time-dependent hazard of combined outcome with corticosteroids. Podocyte hypertrophy and glomeruli with simple adhesions appeared to reflect active lesions associated with a response to corticosteroids, while other S1 lesions defined chronicity. Thus, our findings support subclassifying S1 lesions in IgAN.

Published
2024
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5. The MEST score provides earlier risk prediction in lgA nephropathy

Author

Barbour, Sean J., Espino-Hernandez, Gabriela, Reich, Heather N., Coppo, Rosanna, Roberts, Ian S.D., Feehally, John, Herzenberg, Andrew M., Cattran, Daniel C., Bavbek, N., Cook, T., Troyanov, S., Alpers, C., Amore, A., Barratt, J., Berthoux, F., Bonsib, S., Bruijn, J., D’Agati, V., D’Amico, G., Emancipator, S., Emmal, F., Ferrario, F., Fervenza, F., Florquin, S., Fogo, A., Geddes, C., Groene, H., Haas, M., Hill, P., Hogg, R., Hsu, S., Hunley, T., Hladunewich, M., Jennette, C., Joh, K., Julian, B., Kawamura, T., Lai, F., Leung, C., Li, L., Li, P., Liu, Z., Massat, A., Mackinnon, B., Mezzano, S., Schena, F., Tomino, Y., Walker, P., Wang, H., Weening, J., Yoshikawa, N., Zhang, H., Coppo, R., Troyanov, S., Cattran, D.C., Cook, H.T., Feehally, J., Roberts, I., Tesar, V., Maixnerova, D., Lundberg, S., Gesualdo, L., Emma, F., Fuiano, L., Beltrame, G., Rollino, C., RC, Amore, A., Camilla, R., Peruzzi, L., Praga, M., Feriozzi, S., Polci, R., Segoloni, G., Colla, L., Pani, A., Angioi, A., Piras, L., JF, Cancarini, G., Ravera, S., Durlik, M., Moggia, E., Ballarin, J., Di Giulio, S., Pugliese, F., Serriello, I., Caliskan, Y., Sever, M., Kilicaslan, I., Locatelli, F., Del Vecchio, L., Wetzels, J.F.M., Peters, H., Berg, U., Carvalho, F., da Costa Ferreira, A.C., Maggio, M., Wiecek, A., Ots-Rosenberg, M., Magistroni, R., Topaloglu, R., Bilginer, Y., D’Amico, M., Stangou, M., Giacchino, F., Goumenos, D., Kalliakmani, P., Gerolymos, M., Galesic, K., Geddes, C., Siamopoulos, K., Balafa, O., Galliani, M., Stratta, P., Quaglia, M., Bergia, R., Cravero, R., Salvadori, M., Cirami, L., Fellstrom, B., Kloster Smerud, H., Ferrario, F., Stellato, T., Egido, J., Martin, C., Floege, J., Eitner, F., Lupo, A., Bernich, P., Menè, P., Morosetti, M., van Kooten, C., Rabelink, T., Reinders, M.E.J., Boria Grinyo, J.M., Cusinato, S., Benozzi, L., Savoldi, S., Licata, C., Mizerska-Wasiak, M., Martina, G., Messuerotti, A., Dal Canton, A., Esposito, C., Migotto, C., Triolo, G., Mariano, F., Pozzi, C., Boero, R., Bellur, S., Mazzucco, G., Giannakakis, C., Honsova, E., Sundelin, B., Di Palma, A.M., Ferrario, F., Gutiérrez, E., Asunis, A.M., Barratt, J., Tardanico, R., Perkowska-Ptasinska, A., Arce Terroba, J., Fortunato, M., Pantzaki, A., Ozluk, Y., Steenbergen, E., Soderberg, M., Riispere, Z., Furci, L., Orhan, D., Kipgen, D., Casartelli, D., Galesic Ljubanovic, D., Gakiopoulou, H., Bertoni, E., Cannata Ortiz, P., Karkoszka, H., Groene, H.J., Stoppacciaro, A., Bajema, I., Bruijn, J., Fulladosa Oliveras, X., Maldyk, J., and Ioachim, E.

Abstract

The Oxford Classification of IgA nephropathy (IgAN) includes the following four histologic components: mesangial (M) and endocapillary (E) hypercellularity, segmental sclerosis (S) and interstitial fibrosis/tubular atrophy (T). These combine to form the MEST score and are independently associated with renal outcome. Current prediction and risk stratification in IgAN requires clinical data over 2 years of follow-up. Using modern prediction tools, we examined whether combining MEST with cross-sectional clinical data at biopsy provides earlier risk prediction in IgAN than current best methods that use 2 years of follow-up data. We used a cohort of 901 adults with IgAN from the Oxford derivation and North American validation studies and the VALIGA study followed for a median of 5.6 years to analyze the primary outcome (50% decrease in eGFR or ESRD) using Cox regression models. Covariates of clinical data at biopsy (eGFR, proteinuria, MAP) with or without MEST, and then 2-year clinical data alone (2-year average of proteinuria/MAP, eGFR at biopsy) were considered. There was significant improvement in prediction by adding MEST to clinical data at biopsy. The combination predicted the outcome as well as the 2-year clinical data alone, with comparable calibration curves. This effect did not change in subgroups treated or not with RAS blockade or immunosuppression. Thus, combining the MEST score with cross-sectional clinical data at biopsy provides earlier risk prediction in IgAN than our current best methods.

Published
2016
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6. Prevalence of hypertension in patients on peritoneal dialysis: results of an Italian multicentre study.

Author

Cocchi, R, Degli Esposti, E, Fabbri, A, Lucatello, A, Sturani, A, Quarello, F, Boero, R, Bruno, M, Dadone, C, Favazza, A, Scanziani, R, Tommasi, A, and Giangrande, A

Abstract

The tenet that peritoneal dialysis is capable of either normalizing or improving blood pressure control in uraemic patients is based on outdated or monocentric experiences. Therefore, we assessed the prevalence of hypertension and the efficacy of antihypertensive therapy in a large, multicentric cohort of patients on peritoneal dialysis.

Published
1999
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7. Blood Pressure Behaviour in Hemodialysis Patients Treated for 10 Years

Author

Degli Esposti, E., Boero, R., Chiarini, C., Negroni, D., Quarello, F., Santoro, A., Sturani, A., Zuccalà, A., Piccoli, G., and Zucchelli, P.

Abstract

A longitudinal analysis of blood pressure was performed in 30 patients on hemodialysis for at least 10 years, in order to clarify the long-term outcome of hypertension in dialysis patients. Before the start of the dialysis treatment 22 (73.3%) patients were hypertensive, while, after 10 years, only 5 (16.6%) were still hypertensive. Body weight tended to decrease progressively thoughout the period of observation. Hypertension disappeared in the younger patients while it remained/appeared in those who were order showing the characteristics of systolic hypertension. Except for hematocrit no significant differences in metabolic findings were found between normotensive and hypertensive patients. ECG abnormalities were found to be more frequent after 10 years of dialysis than before the start of treatment. High blood pressure tends to disappear progressively in hemodialysis patients and to be no longer a problem in long-term survivors.

Published
1983
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8. Correlations between Bone Histopathology and Serum Biochemistry in Uremic Patients on Chronic Hemodialysis

Author

Canavese, C., Barolo, S., Gurioli, L., Cadario, A., Portigliatti, M., Isaia, G., Thea, A., Marangella, M., Bongiorno, P., Cavagnino, A., Peona, C., Boero, R., Damicone, M., Cardelli, R., Rossi, P., and Piccoli, G.

Abstract

To define which noninvasive investigations are of value in predicting bone histology, we analyzed transiliac bone specimens (66 biopsies, 14 autopsies) from 80 uremic patients on chronic dialysis. Results were compared with values of different measurements of parathyroid hormone (PTH), alkaline phosphatase (APH), osteocalcin, calcitonin, baseline and post-deferroxamine (DFO) aluminium (Al), - β2microglobulin, ferritin and bone mineral density Among histomorphometric parameters, woven osteoid, active osteoblastic surface and resorption surface showed the best correlations with dynamic and biochemical marks of active bone metabolism. Among biochemical parameters, intact PTH and APH were better related to histomorphometric and dynamic bone parameters than other PTH measurements as well as osteocalcin, while calcitonin was related to no parameters. Stainable Al alone, and not total bone Al content was related to bone histology. Baseline Al was related to lamellar osteoid, while post-DFO Al was related to stainable Al. β2microglobulin was positively related to active osteoid surface and ferritin was inversely related to the mineral apposition rate, while bone mineral density was related only to total bone volume.We conclude that, though definite diagnosis requires the use of histological methods, few simple biochemical parameters may offer insight to the bone metabolic status, useful to the physician in day to day clinical practice.

Published
1998
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9. Aggregation of erythrocyte sodium/lithium countertransport activity in families of patients with immunoglobulin A nephropathy

Author

Fabbri, A., Boero, R., Esposti, E. Degli, Guarena, C., Lucatello, A., Sturani, A., Piccoli, G., and Fusaroli, M.

Abstract

1. We evaluated the inheritance of erythrocyte Na+/Li+ countertransport activity in IgA nephropathy by assessing this parameter in 19 patients with biopsy-proven IgA nephropathy and in their 53 relatives (32 parents and 21 siblings). The possible use of erythrocyte Na+/Li+ countertransport activity as a marker of poor prognosis was also evaluated. 2. A significant correlation was found between ‘familial’ and proband Na+/Li+ countertransport activity, but not between that of spouses. 3. Mean blood pressure, although within the normal range, and Na+/Li+ countertransport activity were significantly higher in patients with proteinuria than in those without proteinuria. 4. Parents of proteinuric patients had a higher Na+/Li+ countertransport activity than parents of non-proteinuric patients. 5. In IgA nephropathy the inheritance of erythrocyte Na+/Li+ countertransport activity was preserved. Therefore genetic factors could play a role in the non-immunological progression of IgA nephropathy.

Published
1992
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