letter to the editor
http://www.kidney-international.org & 2014 International Society of Nephrology
Diffusion-weighted magnetic resonance imaging: a nonnephrotoxic prompt assessment of kidney involvement in IgG4-related disease To the Editor: We acknowledge Zhang et al. for their outstanding review of the new magnetic resonance imaging (MRI) methods in nephrology.1 The authors have described the application of MRI techniques for renal functional imaging in various clinical settings very thoroughly. In prolongation to this excellent review, we would like to share our experience with diffusion-weighted (DW) MRI in assessing renal morphological alterations in two recent cases of immunoglobulin (Ig)G4-related disease. The first was a 65-year-old man who presented with chronic kidney disease. Kidney biopsy showed IgG4-related tubulointerstitial
a
nephritis (TIN). Retrospective analysis of earlier DW MRI images demonstrated bilateral hypointense renal nodules corresponding to water movement restriction.2 The second case was a 47-year-old man referred to the nephrologist because DW MRI (Figure 1a) had shown renal nodules, although renal function was normal.3 Kidney biopsy of nodules detected by DW MRI showed acute IgG4-related TIN with massive inflammatory cell infiltration (Figure 1b), which explained the images of water movement restriction. Our cases illustrate that DW MRI can detect renal morphological alterations in IgG4-related TIN early, thus helping to guide renal biopsy. We agree with the authors that a multidisciplinary approach in the application of this new technique in nephrology clinics should be encouraged for the accurate interpretation of MRI findings and for its correlation with renal physiopathology. 1. 2.
3.
Zhang JL, Morrell G, Rusinek H et al. New magnetic resonance imaging methods in nephrology. Kidney Int 2014; 85: 768–778. Pozdzik A, Broche´riou I, Matos C et al. Azathioprine as successful maintenance therapy in IgG4 related tubulointerstitial nephritis. Clin Kidney J 2012; 5: 225–228. Pozdzik A, Matos C, Rorive S et al. Diffusion-weighted magnetic resonance imaging as a new diagnostic tool of subclinical IgG4 related acute tubulointerstitial nephritis. Clin Kidney J 2013; 6: 235–237.
Agnieszka A. Pozdzik1, Celso Matos2, Sandrine Rorive3, Isabelle Brocheriou4, Myriam Delhaye5 and Joe¨lle L. Nortier1
b
1 Department of Nephrology, Transplantation and Dialysis, Erasme Hospital, Universite´ Libre de Bruxelles, Brussels, Belgium; 2Department of Radiology, Erasme Hospital, Universite´ Libre de Bruxelles, Brussels, Belgium; 3 Department of Pathology, Erasme Hospital, Universite´ Libre de Bruxelles, Brussels, Belgium; 4Department of Pathology, Tenon Hospital, Paris, France and 5Department of Gastroenterology, Erasme Hospital, Universite´ Libre de Bruxelles, Brussels, Belgium Correspondence: Agnieszka A. Pozdzik, Department of Nephrology, Transplantation and Dialysis, Erasme Hospital, Universite´ Libre de Bruxelles, Route de Lennik 808, B 1070 Brussels, Belgium. E-mail: [email protected]
Kidney International (2014) 85, 981; doi:10.1038/ki.2013.540
Figure 1 | Contribution of diffusion-weighted magnetic resonance imaging in the detection of the subclinical stage of IgG4-related acute TIN. (a) Color-coded map of T2-weighted and diffusion-weighted imaging displayed multiple bilateral areas of water movement restriction (red arrows) related to hypercellular content of the renal parenchyma associated with marked thickening of the anterior cortex. Areas of normal renal parenchyma (blue arrow) are also shown. The white arrow indicates ultrasound-guided biopsy of the right kidney. (b) Massive interstitial inflammation with extensive renal tubule destruction and apparently normal glomeruli. (Hematoxylin and eosin staining; original magnification 400.) Kidney International (2014) 85, 981–982
Mesenchymal stem cells attenuate ischemic acute kidney injury by inducing regulatory T cells through splenocyte interactions To the Editor: Hu et al.1 presented an elegant study on the potential role of mesenchymal stem cells (MSCs) in attenuating acute kidney injury in a murine model of ischemia–reperfusion injury. The authors demonstrated that infusion of MSCs was associated with amelioration of ischemic kidney injury in a CD4CD25Foxp3 þ (regulatory T cells (Tregs))-dependent manner. Tregs can be either 981
letter to the editor
natural Tregs or induced Tregs, based on their expression of markers such as Nrp1 and helios. Previously, MSCs were found to be associated with increased prevalence of induced Tregs (iTregs), as manifested by the low expression of the above two markers.2 Would the authors agree that this finding would be important toward identifying the mechanism of the beneficial effect of MSCs in ischemic kidney injury? Moreover, the immunosuppressive mechanism of Tregs can be contact-dependent or -independent (e.g., IL-10- or TGFb-mediated). Would the authors agree that conducting transwell experiments with MSCs and splenocytes might help explain such a mechanism? Was there evidence of increased production of IL-10 or TGFb in the supernatants of coculture experiments? The authors presented data showing that a significant reduction in the percentage of IFNg-producing CD8 (more than CD4) was found in animals treated with MSCs. Subsequent coculture experiments confirmed that such an effect was attributed to the induction of Treg frequency. Previously, MSCs were shown to induce regulatory CD8Foxp3 þ T cells.3 However, the authors did not report on the frequency of CD8Foxp3 þ T cells as a potential explanation for the marked reduction in IFNg þ CD8 T cells. 1.
2.
3.
Hu J, Zhang L, Wang N et al. Mesenchymal stem cells attenuate ischemic acute kidney injury by inducing regulatory T cells through splenocyte interactions. Kidney Int 2013; 84: 521–531. Luz-Crawford P, Noel D, Fernandez X et al. Mesenchymal stem cells repress Th17 molecular program through the PD-1 pathway. PLoS ONE 2012; 7: e45272. Duffy MM, Ritter T, Ceredig R et al. Mesenchymal stem cell effects on T-cell effector pathways. Stem Cell Res Ther 2011; 2: 34.
Dana Kidder1 1
Renal Unit, Ninewells Hospital, Dundee, Scotland, UK Correspondence: Dana Kidder, Renal Unit, Ninewells Hospital, Dundee, Scotland DD1 9SY, UK. E-mail: [email protected]
This study is the first to demonstrate an association between serum b2-M and long-term outcomes in kidney transplant recipients. It is interesting that, about three decades ago, other workers2,3 including ourselves4 reported that serum b2M used alone or with urine b2-M and SUR (serum-to-urine b2-M ratio) appears to be a useful index for assessment of renal allograft function as well as for detection of potential renal damage. In 1983, Edwards et al.5 reported that serum b2-M levels measured up to 48 h before a rise in serum creatinine were accurate in predicting or diagnosing rejection in 91% of all patients. Increased serum b2-M levels may reflect either increased synthesis and/or defect of glomerular filtration. Increased urinary excretion reflects primarily defective tubular reabsorption and/or possible increased filtered load. In the case of the transplanted kidney, this increased urinary b2-M excretion would probably indicate proximal tubular damage due to transplant rejection. The elegant study by Astor et al.1 could have yielded even more intriguing information if b2-M levels had been obtained from both the urine and the serum and the SUR had been calculated. We are in agreement with Astor et al.1 that elevated serum b2-M can be a useful prognostic marker. This is based on our earlier work on immunoglobulin A (IgA) nephritis, which reported that patients with IgA nephritis with glomerular sclerosis have higher levels of serum b2-M, which were correlated with severe proteinuria and intensity of IgA staining on immunofluorescence.6 1.
2.
3.
Kidney International (2014) 85, 981–982; doi:10.1038/ki.2013.562 4.
Serum b2-microglobulin predicts mortality and transplant outcomes To the Editor: We read with great interest the article by Astor et al.,1 which reported that serum b2-microglobulin (b2-M) at discharge is a potent predictor of long-term mortality and graft loss in kidney transplant recipients. Although considered a limitation of the study, nevertheless it is impressive that only one measurement of serum b2-M and serum creatinine at discharge could strongly predict outcomes over a median follow-up period over 5 years.
982
5.
6.
Astor BC, Muth B, Kaufman DB, Pirsch JD, Hofmann RM, Djamali A. Serum b2-microglobulin at discharge predicts mortality and graft loss following kidney transplantation. Kidney Int 2013; 84: 810–817. Schweizer RT, Moore R, Bartus SA, Bow L, Hayden J. Beta 2-microglobulin monitoring after renal transplantation. Transplant Proc 1981; 13: 1620–1623. Ahlmein J. Studies of serum beta-2-microglobulin in the initial postoperative period after clinical transplantation. Scand J Urol Nephrol 1980; 54: 145–149. Woo KT, Lee EJC, Lau YK, Lim CH. Beta-2-microglobulin in the assessment of renal function of the transplanted kidney. Nephron 1985; 39: 223–227. Edwards LC, Helderman JH, Hamm LL, Ludwin D, Gailunas P Jr, Hull AR. Noninvasive monitoring of renal transplant function by analysis of beta-2microglobulin. Kidney Int 1983; 23: 767–770. Woo KT, Tan YO, Yap HK, Lau YK, Tay JSH, Lim CH. Beta-2 microglobulin in mesangial IgA nephropathy. Nephron 1984; 37: 78–81.
Keng-Thye Woo1, Marjorie W.Y. Foo1, H. Lina Choong1, Hui Kim Yap1, Evan J.C. Lee1 and Choong-Meng Chan1 1
Department of Renal Medicine, Singapore General Hospital, Singapore Correspondence: Keng-Thye Woo, Department of Renal Medicine, Singapore General Hospital, Outram Road, Singapore 169608, Singapore. E mail: [email protected] Kidney International (2014) 85, 982; doi:10.1038/ki.2014.7
Kidney International (2014) 85, 981–982
http://www.kidney-international.org & 2014 International Society of Nephrology
Diffusion-weighted magnetic resonance imaging: a nonnephrotoxic prompt assessment of kidney involvement in IgG4-related disease To the Editor: We acknowledge Zhang et al. for their outstanding review of the new magnetic resonance imaging (MRI) methods in nephrology.1 The authors have described the application of MRI techniques for renal functional imaging in various clinical settings very thoroughly. In prolongation to this excellent review, we would like to share our experience with diffusion-weighted (DW) MRI in assessing renal morphological alterations in two recent cases of immunoglobulin (Ig)G4-related disease. The first was a 65-year-old man who presented with chronic kidney disease. Kidney biopsy showed IgG4-related tubulointerstitial
a
nephritis (TIN). Retrospective analysis of earlier DW MRI images demonstrated bilateral hypointense renal nodules corresponding to water movement restriction.2 The second case was a 47-year-old man referred to the nephrologist because DW MRI (Figure 1a) had shown renal nodules, although renal function was normal.3 Kidney biopsy of nodules detected by DW MRI showed acute IgG4-related TIN with massive inflammatory cell infiltration (Figure 1b), which explained the images of water movement restriction. Our cases illustrate that DW MRI can detect renal morphological alterations in IgG4-related TIN early, thus helping to guide renal biopsy. We agree with the authors that a multidisciplinary approach in the application of this new technique in nephrology clinics should be encouraged for the accurate interpretation of MRI findings and for its correlation with renal physiopathology. 1. 2.
3.
Zhang JL, Morrell G, Rusinek H et al. New magnetic resonance imaging methods in nephrology. Kidney Int 2014; 85: 768–778. Pozdzik A, Broche´riou I, Matos C et al. Azathioprine as successful maintenance therapy in IgG4 related tubulointerstitial nephritis. Clin Kidney J 2012; 5: 225–228. Pozdzik A, Matos C, Rorive S et al. Diffusion-weighted magnetic resonance imaging as a new diagnostic tool of subclinical IgG4 related acute tubulointerstitial nephritis. Clin Kidney J 2013; 6: 235–237.
Agnieszka A. Pozdzik1, Celso Matos2, Sandrine Rorive3, Isabelle Brocheriou4, Myriam Delhaye5 and Joe¨lle L. Nortier1
b
1 Department of Nephrology, Transplantation and Dialysis, Erasme Hospital, Universite´ Libre de Bruxelles, Brussels, Belgium; 2Department of Radiology, Erasme Hospital, Universite´ Libre de Bruxelles, Brussels, Belgium; 3 Department of Pathology, Erasme Hospital, Universite´ Libre de Bruxelles, Brussels, Belgium; 4Department of Pathology, Tenon Hospital, Paris, France and 5Department of Gastroenterology, Erasme Hospital, Universite´ Libre de Bruxelles, Brussels, Belgium Correspondence: Agnieszka A. Pozdzik, Department of Nephrology, Transplantation and Dialysis, Erasme Hospital, Universite´ Libre de Bruxelles, Route de Lennik 808, B 1070 Brussels, Belgium. E-mail: [email protected]
Kidney International (2014) 85, 981; doi:10.1038/ki.2013.540
Figure 1 | Contribution of diffusion-weighted magnetic resonance imaging in the detection of the subclinical stage of IgG4-related acute TIN. (a) Color-coded map of T2-weighted and diffusion-weighted imaging displayed multiple bilateral areas of water movement restriction (red arrows) related to hypercellular content of the renal parenchyma associated with marked thickening of the anterior cortex. Areas of normal renal parenchyma (blue arrow) are also shown. The white arrow indicates ultrasound-guided biopsy of the right kidney. (b) Massive interstitial inflammation with extensive renal tubule destruction and apparently normal glomeruli. (Hematoxylin and eosin staining; original magnification 400.) Kidney International (2014) 85, 981–982
Mesenchymal stem cells attenuate ischemic acute kidney injury by inducing regulatory T cells through splenocyte interactions To the Editor: Hu et al.1 presented an elegant study on the potential role of mesenchymal stem cells (MSCs) in attenuating acute kidney injury in a murine model of ischemia–reperfusion injury. The authors demonstrated that infusion of MSCs was associated with amelioration of ischemic kidney injury in a CD4CD25Foxp3 þ (regulatory T cells (Tregs))-dependent manner. Tregs can be either 981
letter to the editor
natural Tregs or induced Tregs, based on their expression of markers such as Nrp1 and helios. Previously, MSCs were found to be associated with increased prevalence of induced Tregs (iTregs), as manifested by the low expression of the above two markers.2 Would the authors agree that this finding would be important toward identifying the mechanism of the beneficial effect of MSCs in ischemic kidney injury? Moreover, the immunosuppressive mechanism of Tregs can be contact-dependent or -independent (e.g., IL-10- or TGFb-mediated). Would the authors agree that conducting transwell experiments with MSCs and splenocytes might help explain such a mechanism? Was there evidence of increased production of IL-10 or TGFb in the supernatants of coculture experiments? The authors presented data showing that a significant reduction in the percentage of IFNg-producing CD8 (more than CD4) was found in animals treated with MSCs. Subsequent coculture experiments confirmed that such an effect was attributed to the induction of Treg frequency. Previously, MSCs were shown to induce regulatory CD8Foxp3 þ T cells.3 However, the authors did not report on the frequency of CD8Foxp3 þ T cells as a potential explanation for the marked reduction in IFNg þ CD8 T cells. 1.
2.
3.
Hu J, Zhang L, Wang N et al. Mesenchymal stem cells attenuate ischemic acute kidney injury by inducing regulatory T cells through splenocyte interactions. Kidney Int 2013; 84: 521–531. Luz-Crawford P, Noel D, Fernandez X et al. Mesenchymal stem cells repress Th17 molecular program through the PD-1 pathway. PLoS ONE 2012; 7: e45272. Duffy MM, Ritter T, Ceredig R et al. Mesenchymal stem cell effects on T-cell effector pathways. Stem Cell Res Ther 2011; 2: 34.
Dana Kidder1 1
Renal Unit, Ninewells Hospital, Dundee, Scotland, UK Correspondence: Dana Kidder, Renal Unit, Ninewells Hospital, Dundee, Scotland DD1 9SY, UK. E-mail: [email protected]
This study is the first to demonstrate an association between serum b2-M and long-term outcomes in kidney transplant recipients. It is interesting that, about three decades ago, other workers2,3 including ourselves4 reported that serum b2M used alone or with urine b2-M and SUR (serum-to-urine b2-M ratio) appears to be a useful index for assessment of renal allograft function as well as for detection of potential renal damage. In 1983, Edwards et al.5 reported that serum b2-M levels measured up to 48 h before a rise in serum creatinine were accurate in predicting or diagnosing rejection in 91% of all patients. Increased serum b2-M levels may reflect either increased synthesis and/or defect of glomerular filtration. Increased urinary excretion reflects primarily defective tubular reabsorption and/or possible increased filtered load. In the case of the transplanted kidney, this increased urinary b2-M excretion would probably indicate proximal tubular damage due to transplant rejection. The elegant study by Astor et al.1 could have yielded even more intriguing information if b2-M levels had been obtained from both the urine and the serum and the SUR had been calculated. We are in agreement with Astor et al.1 that elevated serum b2-M can be a useful prognostic marker. This is based on our earlier work on immunoglobulin A (IgA) nephritis, which reported that patients with IgA nephritis with glomerular sclerosis have higher levels of serum b2-M, which were correlated with severe proteinuria and intensity of IgA staining on immunofluorescence.6 1.
2.
3.
Kidney International (2014) 85, 981–982; doi:10.1038/ki.2013.562 4.
Serum b2-microglobulin predicts mortality and transplant outcomes To the Editor: We read with great interest the article by Astor et al.,1 which reported that serum b2-microglobulin (b2-M) at discharge is a potent predictor of long-term mortality and graft loss in kidney transplant recipients. Although considered a limitation of the study, nevertheless it is impressive that only one measurement of serum b2-M and serum creatinine at discharge could strongly predict outcomes over a median follow-up period over 5 years.
982
5.
6.
Astor BC, Muth B, Kaufman DB, Pirsch JD, Hofmann RM, Djamali A. Serum b2-microglobulin at discharge predicts mortality and graft loss following kidney transplantation. Kidney Int 2013; 84: 810–817. Schweizer RT, Moore R, Bartus SA, Bow L, Hayden J. Beta 2-microglobulin monitoring after renal transplantation. Transplant Proc 1981; 13: 1620–1623. Ahlmein J. Studies of serum beta-2-microglobulin in the initial postoperative period after clinical transplantation. Scand J Urol Nephrol 1980; 54: 145–149. Woo KT, Lee EJC, Lau YK, Lim CH. Beta-2-microglobulin in the assessment of renal function of the transplanted kidney. Nephron 1985; 39: 223–227. Edwards LC, Helderman JH, Hamm LL, Ludwin D, Gailunas P Jr, Hull AR. Noninvasive monitoring of renal transplant function by analysis of beta-2microglobulin. Kidney Int 1983; 23: 767–770. Woo KT, Tan YO, Yap HK, Lau YK, Tay JSH, Lim CH. Beta-2 microglobulin in mesangial IgA nephropathy. Nephron 1984; 37: 78–81.
Keng-Thye Woo1, Marjorie W.Y. Foo1, H. Lina Choong1, Hui Kim Yap1, Evan J.C. Lee1 and Choong-Meng Chan1 1
Department of Renal Medicine, Singapore General Hospital, Singapore Correspondence: Keng-Thye Woo, Department of Renal Medicine, Singapore General Hospital, Outram Road, Singapore 169608, Singapore. E mail: [email protected] Kidney International (2014) 85, 982; doi:10.1038/ki.2014.7
Kidney International (2014) 85, 981–982
