commentary
an adjunct to morphologic diagnosis and in guiding therapy. The potential of studies of peripheral blood is particularly exciting, as these could be performed with greater frequency than those on biopsy tissue, possibly as a means to follow therapeutic responses and evolving patterns of inflammation over time. By contrast, each renal allograft biopsy requires an invasive procedure and produces a ‘snapshot’ of the tissue at a single time point that, while useful in diagnosis, guiding treatment, and predicting clinical outcomes, is limited as a monitoring tool and is subject to sampling variations that in fact may explain some apparent discrepancies between histologic and molecular studies performed on biopsy samples, such as that related to the significance of isolated endarteritis discussed earlier. Perhaps the area in which molecular studies hold the greatest potential is the personalizing of treatment of rejection based on the expression of specific gene sets. Initially this may prove useful in patients failing to respond to standard therapy, but ultimately this could become the standard of care, leading to precise therapeutic regimens that are more effective in preventing and treating rejection, and in reducing complications associated with today’s broad-based immunosuppressive agents. DISCLOSURE
The author declared no competing interests. REFERENCES 1.
2.
3.
4.
5.
464
Mueller TF, Einecke G, Reeve J et al. Microarray analysis of rejection in human kidney transplants using pathogenesis-based transcript sets. Am J Transplant 2007; 7: 2712–2722. Sis B, Jhangri GS, Bunnag S et al. Endothelial gene expression in kidney transplants with alloantibody indicates antibody-mediated damage despite lack of C4d staining. Am J Transplant 2009; 9: 2312–2323. Hidalgo LG, Sis B, Sellares J et al. NK cell transcripts and NK cells in kidney biopsies from patients with donor-specific antibodies: evidence for NK cell involvement in antibodymediated rejection. Am J Transplant 2010; 10: 1812–1822. Loupy A, Suberbielle-Boissel C, Hill GS et al. Outcome of subclinical antibody-mediated rejection in kidney transplant recipients with preformed donor-specific antibodies. Am J Transplant 2009; 9: 2561–2570. Haas M. Pathology of C4d-negative antibody-mediated rejection in renal
6.
7.
8.
9.
10.
allografts. Curr Opin Organ Transplant 2013; 18: 319–326. Haas M, Sis B, Racusen LC et al. Banff 2013 meeting report: inclusion of C4d-negative antibody-mediated rejection and antibodyassociated arterial lesions. Am J Transplant 2014; 14: 272–283. Sellares J, Reeve J, Loupy A et al. Molecular diagnosis of antibody-mediated rejection in human kidney transplants. Am J Transplant 2013; 13: 971–983. Halloran PF, Pereira AB, Chang J et al. Microarray diagnosis of antibody-mediated rejection in kidney transplant biopsies: an international prospective study (INTERCOM). Am J Transplant 2013; 13: 2865–2874. Reeve J, Sellares J, Mengel M et al. Molecular diagnosis of T cell-mediated rejection in human kidney transplant biopsies. Am J Transplant 2013; 13: 645–655. Halloran PF, Pereira AB, Chang J et al. Potential impact of microarray diagnosis of T cell-mediated rejection in kidney
11.
12.
13.
14.
transplants: the INTERCOM study. Am J Transplant 2013; 13: 2352–2363. Hayde N, Broin PO´, Bao Y et al. Increased intragraft rejection–associated gene transcripts in patients with donor-specific antibodies and normal biopsies. Kidney Int 2014; 86: 600–609. de Kort H, Willicombe M, Brookes P et al. Microcirculation inflammation associates with outcome in renal transplant patients with de novo donor-specific antibodies. Am J Transplant 2013; 13: 485–492. Wiebe C, Gibson IW, Blydt-Hansen TD et al. Evolution and clinical pathologic correlations of de novo donor-specific HLA antibody post kidney transplant. Am J Transplant 2012; 12: 1157–1167. Kahwaji J, Najjar R, Kancherla D et al. Histopathologic features of transplant glomerulopathy associated with response to therapy with intravenous immune globulin and rituximab. Clin Transplant 2014; 28: 546–553.
see clinical investigation on page 610
Is it time to increase access to transplantation for those with diabetic end-stage kidney disease? Steven J. Chadban1 and Natalie D. Staplin2 Keddis et al. present a large, single-center experience that demonstrates improvement over time in survival of patients with diabetes and endstage kidney disease who receive a kidney transplant. We discuss how these data should prompt transplant programs to consider providing greater access to transplantation for their patients with diabetes. Kidney International (2014) 86, 464–466. doi:10.1038/ki.2014.154
The number of people worldwide with type 2 diabetes mellitus has more than doubled over the past three decades and, according to International 1 Department of Renal Medicine, Royal Prince Alfred Hospital and University of Sydney, Camperdown, New South Wales, Australia and 2 Clinical Trial Service Unit and Epidemiological Studies Unit, University of Oxford, Oxford, UK Correspondence: Steven J. Chadban, Department of Renal Medicine, Royal Prince Alfred Hospital and University of Sydney, Missenden Road, Camperdown, New South Wales 2093, Australia. E-mail: [email protected]
Diabetes Federation projections, will reach 592 million by 2035.1 Analysis of serial National Health and Nutrition Examination Surveys (NHANES) of the US population has demonstrated that as prevalence of diabetes rises, the number of people with evidence of diabetic kidney disease rises in parallel, indicating that 35% of people with T2DM have CKD.2 It is therefore no surprise that diabetes is the leading cause of end-stage kidney disease in most countries (DM-ESKD). Although recent trends toward stabilization in the incidence of DM-ESKD in several Kidney International (2014) 86
commentary
countries give some cause for optimism, the incidence in countries such as the United Kingdom, Norway, and Australia more than doubled between 2000 and 2010.3,4 For the vast and increasing number of people with DM-ESKD worldwide who are able to access renal replacement therapy, dialysis will be their mode of treatment for the remainder of their life. People with DM-ESKD, as opposed to other causes of ESKD, have vastly reduced access to transplantation. US Renal Data System (USRDS) data indicate that 18.4% of people with DM-ESKD were sustained by a functioning kidney transplant, as compared with 53.3% of those with ESKD caused by glomerulonephritis.3 Inferior patient and graft survival in those with diabetes, compared with other causes of ESKD, likely provides the major barrier to transplantation access. An analysis from the Australia and New Zealand Dialysis and Transplant (ANZDATA) Registry (Figure 1) demonstrates inferior patient survival in those with DM-ESKD as compared with those with glomerulonephritis who received a deceased-donor kidney transplant between 2000 and 2011, with divergence in survival evident within the first year after transplantation and increasing with follow-up duration. In the United States, the USRDS reports adjusted 10 year graft survival of 35.8% vs. 47.4 and 49.4% vs. 60.5% for patients with diabetes vs. glomerulonephritis, following deceased- and livingdonor transplantation, respectively.3 Analyses adjusted for age, sex, ethnicity, and vintage also demonstrated higher mortality after transplantation for those with DM-ESKD (170.8 per 1000 patient-years) vs. glomerulonephritis (96.3 per 1000 patient-years).3 Against this background, the report by Keddis et al.5 (this issue) offers some hope of improvement in transplantation outcomes for people with diabetes and ESKD. The authors report their experience with 1688 kidney-only recipients, of whom 413 (24.5%) had diabetes diagnosed before transplantation (DM), who underwent transplantation between 1996 and 2007 with Kidney International (2014) 86
1.00
0.75
0.50 Primary disease GN
0.25
Diabetes Other 0 0
5
10
15
Years
Figure 1 | Impact of diabetes on post-transplantation patient survival in Australia. Among recipients of a first kidney-alone transplantation performed between 1998 and 2012, patient survival in those with a primary diagnosis of diabetic nephropathy (n ¼ 978) was inferior to that in those with glomerulonephritis (GN) (n ¼ 3985) and those with other diagnoses (n ¼ 3745) (log rank w2 Po0.0001). Data were sourced from the ANZDATA Registry and analyzed by Phil Clayton (ANZDATA Registry).
5 years of follow-up. In the non-DM group, death rates and causes of death remained unchanged across the study period. For those with DM, although overall mortality across the entire study period was more than twofold higher (hazard ratio 2.68 vs. no-DM at 5 years follow-up), the difference has been attenuated in recent years because of significant reductions in the incidence of cardiac events and infectious deaths. For DM, 5-year all-cause mortality fell from 24.1% during 1996–2002 to 11.9% during 2003–2007, compared with 7.1 and 5.9% for the same periods in the no-DM group. The rate of major cardiovascular events remained higher in DM during the first year after transplantation but fell to rates equal to those of the no-DM group for years 2–5 after transplantation in the latest era. This did not appear to be due to changes in selection criteria over time, as pretransplantation risk profile and cardiac assessment protocols remained unchanged. Death-censored graft failure rates were not different between the DM-ESKD and no-DM groups. Improvements in the use of cardioprotective medications and glycemic control, graft function, and serum albumin were all apparent over time, and the authors postulated that the observed improvements in survival may
be attributable to better post-transplantation management. Two design flaws limit the strength of this study. Firstly, all data were captured retrospectively by review of case notes and medical records, thereby creating potential for bias. Secondly, the authors were not able to define the incidence of new-onset diabetes after transplantation (NODAT). The key impact of NODAT is on survival, with one analysis of the USRDS demonstrating significantly inferior survival in those requiring treatment for NODAT.6 By definition, only those who were free from diabetes before transplantation would have been at risk of NODAT, creating a potential source of bias in determining hazards of mortality for DM relative to no-DM. As the authors acknowledge, specific limitations in the study by Keddis et al.5 limit the generalizability of their observations. Patients were allocated to the DM group if the medical records listed a diagnosis of diabetes or indicated usage of antihyperglycemic drugs. Thus, this was a comparison of DM vs. no-DM, rather than ESKD caused by diabetes vs. not. The cohort was 92% Caucasian, received a livedonor kidney in 76% of cases, and waited a median of only 4 months on dialysis prior to transplantation. 465
commentary
Induction with T cell-depleting antibodies was used in 83% of recipients, and 76% of patients received tacrolimus, mycophenolate, and prednisone for maintenance immunosuppression. As ethnicity, duration of dialysis prior to transplantation, donor source, and immunosuppression may all impact outcomes and potentially modify the effects of diabetes, the results may be less applicable to programs with largely non-Caucasian populations, a higher proportion of deceased donors, longer waiting times, or different immunosuppressive protocols. The data presented clearly demonstrate that excellent transplant outcomes are achievable for a significant proportion of patients with diabetes and ESKD, and thus diabetes should not be viewed as a contraindication to kidney transplantation. Should we then, on the basis of these data, liberalize access to transplantation for diabetic patients with ESKD? The authors, quite reasonably, suggest we should ‘give consideration’ to this. In doing so, we must consider more than just crude patient survival. Indeed, modeling studies that have examined incremental costs and benefits of transplantation vs. dialysis demonstrate that wait-listing and giving transplants to patients with diabetes is highly cost-effective and prolongs life, relative to nonlisting.7 The impacts of transplantation on recipient quality of life, carer and family life, cost of care to society, and opportunity cost for those not given transplants all warrant close consideration. Substantial changes to wait-listing policy and organ allocation require modeling of data obtained from registries and cohort studies, informed by ethical and societal considerations, to determine the outcomes of those given and those not given transplants. To this end, the data provided by Keddis et al.5 make an important contribution. DISCLOSURE
The authors declared no competing interests. ACKNOWLEDGMENTS
The authors thank Phil Clayton for his analysis of data sourced from the ANZDATA 466
Registry and Sarah White for critical appraisal of the manuscript.
4.
REFERENCES 1.
2.
3.
International Diabetes Federation. IDF Diabetes Atlas, 6th edn. International Diabetes Federation: Brussels, Belgium, 2013. http:// www.idf.org/diabetesatlas. De Boer IH, Rue TC, Hall YN et al. Temporal trends in the prevalence of diabetic kidney disease in the United States. JAMA 2011; 305: 2532–2539. US Renal Data System. 2013 Annual Data Report. National Institute of Diabetes and Digestive and Kidney Diseases. National Institutes of Health: Bethesda, MD, USA (www.usrds.org/2013/view/Default.aspx) 2013.
5.
6.
7.
ERA-EDTA Annual Report 2011. European Renal Association and European Dialysis and Transplant Association Amsterdam, the Netherlands (www.era-edta-reg.org) 2011. Keddis MT, El Ters M, Rodrigo E et al. Enhanced posttransplant management of patients with diabetes improves patient outcomes. Kidney Int 2014; 86: 610–618. Cole EH, Johnston O, Rose CL et al. Impact of acute rejection and new-onset diabetes on long-term transplant graft and patient survival. Clin J Am Soc Nephrol 2008; 3: 814–821. Wong G, Howard K, Chapman JR et al. Comparative survival and economic benefits of deceased donor kidney transplantation and dialysis in people with varying ages and co-morbidities. PLoS One [online] 2012; 7: e29591.
see clinical investigation on page 619
Novel evidence on hepatitis C virus–associated glomerular disease Fabrizio Fabrizi1,2, Piergiorgio Messa1 and Paul Martin2 A large spectrum of renal pathology is associated with hepatitis C virus (HCV). According to novel evidence, occult HCV infection (HCV-RNA in peripheral blood mononuclear cells or in serum after ultracentrifugation) could be involved in the pathogenesis of glomerular nephropathy among patients negative for conventional markers of HCV. Additional studies with appropriate size and technology are in progress to confirm the relationship between occult HCV and glomerular disease, which has multiple implications from the clinical standpoint. Kidney International (2014) 86, 466–469. doi:10.1038/ki.2014.181
Hepatitis C virus (HCV) has an estimated prevalence of 3% worldwide (around 170 million infected individuals all over the world) and remains a major global health burden. The long-term hepatic impact of HCV infection includes chronic hepatitis, and cirrhosis, with or without hepatocellular carcinoma. Several extrahepatic 1 Division of Nephrology, Maggiore Hospital and IRCCS Foundation, Milano, Italy and 2Division of Hepatology, School of Medicine, University of Miami, Miami, Florida, USA Correspondence: Fabrizio Fabrizi, Division of Nephrology, Maggiore Hospital, IRCCS Foundation, Padiglione Croff, Via Commenda 15, 20122 Milano, Italy. E-mail: [email protected]
manifestations have been associated with HCV infection, including hematologic, dermatologic, autoimmune, and kidney diseases. There is increasing evidence of an association between HCV infection and glomerular disease both in native kidneys and after kidney (or liver) transplantation. The most common type of HCV-related glomerulonephritis is type I membranoproliferative glomerulonephritis, usually in the context of type II cryoglobulinemia. HCV-infected patients show less common glomerular diseases including membranoproliferative glomerulonephritis without cryoglobulinemia, membranous nephropathy, focal segmental Kidney International (2014) 86
an adjunct to morphologic diagnosis and in guiding therapy. The potential of studies of peripheral blood is particularly exciting, as these could be performed with greater frequency than those on biopsy tissue, possibly as a means to follow therapeutic responses and evolving patterns of inflammation over time. By contrast, each renal allograft biopsy requires an invasive procedure and produces a ‘snapshot’ of the tissue at a single time point that, while useful in diagnosis, guiding treatment, and predicting clinical outcomes, is limited as a monitoring tool and is subject to sampling variations that in fact may explain some apparent discrepancies between histologic and molecular studies performed on biopsy samples, such as that related to the significance of isolated endarteritis discussed earlier. Perhaps the area in which molecular studies hold the greatest potential is the personalizing of treatment of rejection based on the expression of specific gene sets. Initially this may prove useful in patients failing to respond to standard therapy, but ultimately this could become the standard of care, leading to precise therapeutic regimens that are more effective in preventing and treating rejection, and in reducing complications associated with today’s broad-based immunosuppressive agents. DISCLOSURE
The author declared no competing interests. REFERENCES 1.
2.
3.
4.
5.
464
Mueller TF, Einecke G, Reeve J et al. Microarray analysis of rejection in human kidney transplants using pathogenesis-based transcript sets. Am J Transplant 2007; 7: 2712–2722. Sis B, Jhangri GS, Bunnag S et al. Endothelial gene expression in kidney transplants with alloantibody indicates antibody-mediated damage despite lack of C4d staining. Am J Transplant 2009; 9: 2312–2323. Hidalgo LG, Sis B, Sellares J et al. NK cell transcripts and NK cells in kidney biopsies from patients with donor-specific antibodies: evidence for NK cell involvement in antibodymediated rejection. Am J Transplant 2010; 10: 1812–1822. Loupy A, Suberbielle-Boissel C, Hill GS et al. Outcome of subclinical antibody-mediated rejection in kidney transplant recipients with preformed donor-specific antibodies. Am J Transplant 2009; 9: 2561–2570. Haas M. Pathology of C4d-negative antibody-mediated rejection in renal
6.
7.
8.
9.
10.
allografts. Curr Opin Organ Transplant 2013; 18: 319–326. Haas M, Sis B, Racusen LC et al. Banff 2013 meeting report: inclusion of C4d-negative antibody-mediated rejection and antibodyassociated arterial lesions. Am J Transplant 2014; 14: 272–283. Sellares J, Reeve J, Loupy A et al. Molecular diagnosis of antibody-mediated rejection in human kidney transplants. Am J Transplant 2013; 13: 971–983. Halloran PF, Pereira AB, Chang J et al. Microarray diagnosis of antibody-mediated rejection in kidney transplant biopsies: an international prospective study (INTERCOM). Am J Transplant 2013; 13: 2865–2874. Reeve J, Sellares J, Mengel M et al. Molecular diagnosis of T cell-mediated rejection in human kidney transplant biopsies. Am J Transplant 2013; 13: 645–655. Halloran PF, Pereira AB, Chang J et al. Potential impact of microarray diagnosis of T cell-mediated rejection in kidney
11.
12.
13.
14.
transplants: the INTERCOM study. Am J Transplant 2013; 13: 2352–2363. Hayde N, Broin PO´, Bao Y et al. Increased intragraft rejection–associated gene transcripts in patients with donor-specific antibodies and normal biopsies. Kidney Int 2014; 86: 600–609. de Kort H, Willicombe M, Brookes P et al. Microcirculation inflammation associates with outcome in renal transplant patients with de novo donor-specific antibodies. Am J Transplant 2013; 13: 485–492. Wiebe C, Gibson IW, Blydt-Hansen TD et al. Evolution and clinical pathologic correlations of de novo donor-specific HLA antibody post kidney transplant. Am J Transplant 2012; 12: 1157–1167. Kahwaji J, Najjar R, Kancherla D et al. Histopathologic features of transplant glomerulopathy associated with response to therapy with intravenous immune globulin and rituximab. Clin Transplant 2014; 28: 546–553.
see clinical investigation on page 610
Is it time to increase access to transplantation for those with diabetic end-stage kidney disease? Steven J. Chadban1 and Natalie D. Staplin2 Keddis et al. present a large, single-center experience that demonstrates improvement over time in survival of patients with diabetes and endstage kidney disease who receive a kidney transplant. We discuss how these data should prompt transplant programs to consider providing greater access to transplantation for their patients with diabetes. Kidney International (2014) 86, 464–466. doi:10.1038/ki.2014.154
The number of people worldwide with type 2 diabetes mellitus has more than doubled over the past three decades and, according to International 1 Department of Renal Medicine, Royal Prince Alfred Hospital and University of Sydney, Camperdown, New South Wales, Australia and 2 Clinical Trial Service Unit and Epidemiological Studies Unit, University of Oxford, Oxford, UK Correspondence: Steven J. Chadban, Department of Renal Medicine, Royal Prince Alfred Hospital and University of Sydney, Missenden Road, Camperdown, New South Wales 2093, Australia. E-mail: [email protected]
Diabetes Federation projections, will reach 592 million by 2035.1 Analysis of serial National Health and Nutrition Examination Surveys (NHANES) of the US population has demonstrated that as prevalence of diabetes rises, the number of people with evidence of diabetic kidney disease rises in parallel, indicating that 35% of people with T2DM have CKD.2 It is therefore no surprise that diabetes is the leading cause of end-stage kidney disease in most countries (DM-ESKD). Although recent trends toward stabilization in the incidence of DM-ESKD in several Kidney International (2014) 86
commentary
countries give some cause for optimism, the incidence in countries such as the United Kingdom, Norway, and Australia more than doubled between 2000 and 2010.3,4 For the vast and increasing number of people with DM-ESKD worldwide who are able to access renal replacement therapy, dialysis will be their mode of treatment for the remainder of their life. People with DM-ESKD, as opposed to other causes of ESKD, have vastly reduced access to transplantation. US Renal Data System (USRDS) data indicate that 18.4% of people with DM-ESKD were sustained by a functioning kidney transplant, as compared with 53.3% of those with ESKD caused by glomerulonephritis.3 Inferior patient and graft survival in those with diabetes, compared with other causes of ESKD, likely provides the major barrier to transplantation access. An analysis from the Australia and New Zealand Dialysis and Transplant (ANZDATA) Registry (Figure 1) demonstrates inferior patient survival in those with DM-ESKD as compared with those with glomerulonephritis who received a deceased-donor kidney transplant between 2000 and 2011, with divergence in survival evident within the first year after transplantation and increasing with follow-up duration. In the United States, the USRDS reports adjusted 10 year graft survival of 35.8% vs. 47.4 and 49.4% vs. 60.5% for patients with diabetes vs. glomerulonephritis, following deceased- and livingdonor transplantation, respectively.3 Analyses adjusted for age, sex, ethnicity, and vintage also demonstrated higher mortality after transplantation for those with DM-ESKD (170.8 per 1000 patient-years) vs. glomerulonephritis (96.3 per 1000 patient-years).3 Against this background, the report by Keddis et al.5 (this issue) offers some hope of improvement in transplantation outcomes for people with diabetes and ESKD. The authors report their experience with 1688 kidney-only recipients, of whom 413 (24.5%) had diabetes diagnosed before transplantation (DM), who underwent transplantation between 1996 and 2007 with Kidney International (2014) 86
1.00
0.75
0.50 Primary disease GN
0.25
Diabetes Other 0 0
5
10
15
Years
Figure 1 | Impact of diabetes on post-transplantation patient survival in Australia. Among recipients of a first kidney-alone transplantation performed between 1998 and 2012, patient survival in those with a primary diagnosis of diabetic nephropathy (n ¼ 978) was inferior to that in those with glomerulonephritis (GN) (n ¼ 3985) and those with other diagnoses (n ¼ 3745) (log rank w2 Po0.0001). Data were sourced from the ANZDATA Registry and analyzed by Phil Clayton (ANZDATA Registry).
5 years of follow-up. In the non-DM group, death rates and causes of death remained unchanged across the study period. For those with DM, although overall mortality across the entire study period was more than twofold higher (hazard ratio 2.68 vs. no-DM at 5 years follow-up), the difference has been attenuated in recent years because of significant reductions in the incidence of cardiac events and infectious deaths. For DM, 5-year all-cause mortality fell from 24.1% during 1996–2002 to 11.9% during 2003–2007, compared with 7.1 and 5.9% for the same periods in the no-DM group. The rate of major cardiovascular events remained higher in DM during the first year after transplantation but fell to rates equal to those of the no-DM group for years 2–5 after transplantation in the latest era. This did not appear to be due to changes in selection criteria over time, as pretransplantation risk profile and cardiac assessment protocols remained unchanged. Death-censored graft failure rates were not different between the DM-ESKD and no-DM groups. Improvements in the use of cardioprotective medications and glycemic control, graft function, and serum albumin were all apparent over time, and the authors postulated that the observed improvements in survival may
be attributable to better post-transplantation management. Two design flaws limit the strength of this study. Firstly, all data were captured retrospectively by review of case notes and medical records, thereby creating potential for bias. Secondly, the authors were not able to define the incidence of new-onset diabetes after transplantation (NODAT). The key impact of NODAT is on survival, with one analysis of the USRDS demonstrating significantly inferior survival in those requiring treatment for NODAT.6 By definition, only those who were free from diabetes before transplantation would have been at risk of NODAT, creating a potential source of bias in determining hazards of mortality for DM relative to no-DM. As the authors acknowledge, specific limitations in the study by Keddis et al.5 limit the generalizability of their observations. Patients were allocated to the DM group if the medical records listed a diagnosis of diabetes or indicated usage of antihyperglycemic drugs. Thus, this was a comparison of DM vs. no-DM, rather than ESKD caused by diabetes vs. not. The cohort was 92% Caucasian, received a livedonor kidney in 76% of cases, and waited a median of only 4 months on dialysis prior to transplantation. 465
commentary
Induction with T cell-depleting antibodies was used in 83% of recipients, and 76% of patients received tacrolimus, mycophenolate, and prednisone for maintenance immunosuppression. As ethnicity, duration of dialysis prior to transplantation, donor source, and immunosuppression may all impact outcomes and potentially modify the effects of diabetes, the results may be less applicable to programs with largely non-Caucasian populations, a higher proportion of deceased donors, longer waiting times, or different immunosuppressive protocols. The data presented clearly demonstrate that excellent transplant outcomes are achievable for a significant proportion of patients with diabetes and ESKD, and thus diabetes should not be viewed as a contraindication to kidney transplantation. Should we then, on the basis of these data, liberalize access to transplantation for diabetic patients with ESKD? The authors, quite reasonably, suggest we should ‘give consideration’ to this. In doing so, we must consider more than just crude patient survival. Indeed, modeling studies that have examined incremental costs and benefits of transplantation vs. dialysis demonstrate that wait-listing and giving transplants to patients with diabetes is highly cost-effective and prolongs life, relative to nonlisting.7 The impacts of transplantation on recipient quality of life, carer and family life, cost of care to society, and opportunity cost for those not given transplants all warrant close consideration. Substantial changes to wait-listing policy and organ allocation require modeling of data obtained from registries and cohort studies, informed by ethical and societal considerations, to determine the outcomes of those given and those not given transplants. To this end, the data provided by Keddis et al.5 make an important contribution. DISCLOSURE
The authors declared no competing interests. ACKNOWLEDGMENTS
The authors thank Phil Clayton for his analysis of data sourced from the ANZDATA 466
Registry and Sarah White for critical appraisal of the manuscript.
4.
REFERENCES 1.
2.
3.
International Diabetes Federation. IDF Diabetes Atlas, 6th edn. International Diabetes Federation: Brussels, Belgium, 2013. http:// www.idf.org/diabetesatlas. De Boer IH, Rue TC, Hall YN et al. Temporal trends in the prevalence of diabetic kidney disease in the United States. JAMA 2011; 305: 2532–2539. US Renal Data System. 2013 Annual Data Report. National Institute of Diabetes and Digestive and Kidney Diseases. National Institutes of Health: Bethesda, MD, USA (www.usrds.org/2013/view/Default.aspx) 2013.
5.
6.
7.
ERA-EDTA Annual Report 2011. European Renal Association and European Dialysis and Transplant Association Amsterdam, the Netherlands (www.era-edta-reg.org) 2011. Keddis MT, El Ters M, Rodrigo E et al. Enhanced posttransplant management of patients with diabetes improves patient outcomes. Kidney Int 2014; 86: 610–618. Cole EH, Johnston O, Rose CL et al. Impact of acute rejection and new-onset diabetes on long-term transplant graft and patient survival. Clin J Am Soc Nephrol 2008; 3: 814–821. Wong G, Howard K, Chapman JR et al. Comparative survival and economic benefits of deceased donor kidney transplantation and dialysis in people with varying ages and co-morbidities. PLoS One [online] 2012; 7: e29591.
see clinical investigation on page 619
Novel evidence on hepatitis C virus–associated glomerular disease Fabrizio Fabrizi1,2, Piergiorgio Messa1 and Paul Martin2 A large spectrum of renal pathology is associated with hepatitis C virus (HCV). According to novel evidence, occult HCV infection (HCV-RNA in peripheral blood mononuclear cells or in serum after ultracentrifugation) could be involved in the pathogenesis of glomerular nephropathy among patients negative for conventional markers of HCV. Additional studies with appropriate size and technology are in progress to confirm the relationship between occult HCV and glomerular disease, which has multiple implications from the clinical standpoint. Kidney International (2014) 86, 466–469. doi:10.1038/ki.2014.181
Hepatitis C virus (HCV) has an estimated prevalence of 3% worldwide (around 170 million infected individuals all over the world) and remains a major global health burden. The long-term hepatic impact of HCV infection includes chronic hepatitis, and cirrhosis, with or without hepatocellular carcinoma. Several extrahepatic 1 Division of Nephrology, Maggiore Hospital and IRCCS Foundation, Milano, Italy and 2Division of Hepatology, School of Medicine, University of Miami, Miami, Florida, USA Correspondence: Fabrizio Fabrizi, Division of Nephrology, Maggiore Hospital, IRCCS Foundation, Padiglione Croff, Via Commenda 15, 20122 Milano, Italy. E-mail: [email protected]
manifestations have been associated with HCV infection, including hematologic, dermatologic, autoimmune, and kidney diseases. There is increasing evidence of an association between HCV infection and glomerular disease both in native kidneys and after kidney (or liver) transplantation. The most common type of HCV-related glomerulonephritis is type I membranoproliferative glomerulonephritis, usually in the context of type II cryoglobulinemia. HCV-infected patients show less common glomerular diseases including membranoproliferative glomerulonephritis without cryoglobulinemia, membranous nephropathy, focal segmental Kidney International (2014) 86
