- Email: [email protected]
Concomitance of IgA Nephropathy and Diabetic Nephropathy in a Kidney Allograft: Case Report and Review of the Literature
Concomitance of IgA Nephropathy and Diabetic Nephropathy in a Kidney Allograft: Case Report and Review of the Literature L. Kamala, S. Salvatorea, C. Hartonoa,b, and A. Perlmana,b,* a
New York Presbyterian HospitaleCornell Medical College, New York, New York; bThe Rogosin Institute, New York, New York
ABSTRACT Whereas diabetic nephropathy is the most common cause of end-stage renal disease (ESRD), IgA nephropathy is the most common glomerulonephritis in the world. We report a case of a kidney transplant recipient whose native renal disease was presumptive diabetic nephropathy. Five years after transplantation, the patient developed proteinuria, hematuria, and allograft dysfunction. Transplant biopsy revealed IgA nephropathy superimposed on diabetic nephropathy.
P
OST-TRANSPLANTATION proteinuria is common among transplant recipients. It has been estimated that w43% of renal transplant recipients develop proteinuria of >1 g/d [1]. It is most commonly caused by chronic allograft injury with glomerulosclerosis (with or without transplant glomerulopathy). Post-transplantation glomerulonephritis, either recurrent or de novo, also is an important cause of post-transplantation proteinuria with or without allograft dysfunction. However, the exact prevalence of post-transplantation glomerulonephritis is not well determined. In a transplant recipient, urinalysis may not be performed routinely and proteinuria can be missed. Even if proteinuria is detected, it might be evaluated differently than the one that occurs in the native kidney. Additionally, immunofluorescence and electron microscopy might not be routinely performed on the biopsy specimen [2]. IgA nephropathy (IgAN) is the most common glomerulonephritis in the world. It is most common in Asians. It is characterized by dominant IgA deposits by immunofluorescence in the mesangial areas [3]. The deposited IgA immunoglobulins have a poorly O-galactosylated hinge region, which increases their tendency to aggregate and form antigen-antibody complexes with IgG directed against the hinge region [4]. IgAN is known for its tendency to recur in the allograft after renal transplantation. The rate of recurrence and the effect it has on allograft survival are difficult to determine owing to a lack of prospective studies involving protocol biopsies. We herein describe a case of IgAN detected in a renal transplant recipient whose original renal disease was presumably secondary to diabetic nephropathy.
CASE REPORT We are reporting a case of a 68-year-old white man with longstanding poorly controlled diabetes, diabetic retinopathy, hypertension with left ventricular hypertrophy and diastolic dysfunction, coronary artery disease, and morbid obesity, who had chronic kidney disease with nephrotic range proteinuria that ultimately progressed to end-stage renal disease (ESRD). The patient’s clinical presentation, which included progressive proteinuric renal impairment in the setting of diabetes with advanced end-organ sequelae, such as retinopathy, without any atypical features for alternative diagnoses, strongly suggested diabetic nephropathy as the etiology for his renal disease. He required hemodialysis for 1 year, followed by a 6eHLA antigen mismatch renal transplant from an expanded-criteria donor, with thymoglobulin induction. His transplant course was notable for delayed graft function requiring dialysis support, but then he recovered normal renal function. His post-transplantation medications included tacrolimus and mycophenolate. He did not receive prednisone maintenance. Five years after the transplantation, his serum creatinine started to increase, and he developed new-onset subnephroticrange proteinuria (protein/creatinine ratio, 1 g/g on spot urine) along with microscopic hematuria. At the same time, he reported frothy urine and leg swelling, but no gross hematuria. His blood pressure was 128/70 mm Hg, and his physical examination was notable for 1þ pitting edema involving both legs. His family history was significant for diabetes, but there was no family history of renal disease. Serum creatinine increased from a baseline of 1 mg/ dL to 2 mg/dL, prompting a renal biopsy. The renal biopsy was notable for mild class II diabetic nephropathy, evidenced by mesangial expansion and glomerular basement membrane *Address correspondence to Alan Perlman, MD, Rogosin Institute, New York Presbyterian HospitaleCornell Medical College, 505 E. 70th Street, HT- 226, New York, New York, 10021. E-mail: [email protected]
0041-1345/14 http://dx.doi.org/10.1016/j.transproceed.2014.06.048
ª 2014 by Elsevier Inc. All rights reserved. 360 Park Avenue South, New York, NY 10010-1710
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Transplantation Proceedings, 46, 2396e2399 (2014)
CONCOMITANCE OF IgA NEPHROPATHY AND DIABETIC NEPHROPATHY
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Fig 1. Glomerulus with mild expansion of mesangial matrix and minimal mesangial hypercellularity (H&E, 40x).
thickening (Figs 1 and 3). Immunofluorescence showed 3þ granular IgA and 3þ C3 deposition, mainly along the glomerular mesangial areas in a global distribution consistent with IgA nephropathy (Fig 2). C4d staining was negative and there was no evidence of cellular or antibody mediated rejection. These findings were highly consistent with IgA nephropathy.
DISCUSSION
The prevalence of post-transplantation glomerulonephritis is not exactly known. Reasons include the different approaches that transplant centers take toward the evaluation of proteinuria and allograft dysfunction that occur in the 12 months after transplantation. Proteinuria or increased creatinine are often attributed to what was previously recognized as “chronic allograft nephropathy” or nonspecific interstitial fibrosis and tubular atrophy, and urinalysis to detect hematuria or active urine sediment may
Fig 2. Immunofluorescence microscopy revealing granular 3þ staining of the mesangium for anti-IgA. (IgA, 40x).
Fig 3. Electron microscopic image showing irregular thickening of the glomerular basement membranes as well as endothelial cell swelling, subendothelial widening with focal new basement membrane formation. Small paramesangial electron dense deposits are also present. (EM, 6000x).
not be routinely performed. Furthermore, it is even harder to differentiate between de novo or recurrent glomerulonephritis, because the kidney recipient’s native disease is frequently not biopsy proven. Glomerulonephritis identified in the allograft may be due also to an unidentified donor disease, and biopsies of the donor kidney are rarely done at the time of implantation. Prevalence of posttransplantation glomerulonephritis ranges from 3% to 13% according to different reports [5]. In a study of 74 renal transplant recipients with post-transplantation nephrotic syndrome, de novo glomerular diseases accounted for 24% of the cases and recurrent glomerular diseases for 20%. Among the 15 cases of recurrent glomerular diseases, 6 cases were due to IgAN, and 2 patients had IgAN among the 18 cases of “de novo” glomerular diseases. In 9 cases the native kidney disease was unknown, and 2 of these 9 patients had IgAN. Of note, in 10% of the patients, the original kidney disease was secondary to diabetic nephropathy [1]. IgAN can lead to ESRD in 25% of cases [6]. IgAN is known for its high recurrence rate after transplantation. The rate of recurrence ranges from 13% to 60% and varies between different series depending on the timing of the biopsy and on whether it is a clinical or histologic recurrence [7]. The rate of histologic recurrence can be as high as 50%e60% [6]. Clinical recurrent IgAN is characterized by proteinuria of >500 mg/d, microscopic hematuria, and
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mesangioproliferative glomerulonephritis on kidney biopsy. Recurrent IgAN is not a benign condition; it has been demonstrated to progress to graft dysfunction and loss of graft in up to 16% of cases [2]. However, the incidence of graft dysfunction in recurrent IgAN varies from one report to another. In a series of 106 patients with IgAN, Ponticelli et al found a biopsy-proven recurrence rate of 35%, and the recurrence did not affect the 10-year graft survival and was not associated with increased risk of graft failure [8]. IgAN recurrence does not appear to be preventable by immunosuppressive drugs, including mycophenolate (MMF) [8]. Although MMF has been shown to modify the course of the disease [9], this was not proven in a 3-year randomized controlled trial of MMF in IgAN that showed a lack of efficacy of MMF on renal function or proteinuria [1]. The present patient’s underlying cause of ESRD was presumably diabetic nephropathy, given the history of uncontrolled diabetes with definitive end-organ sequelae of diabetic retinopathy, in the setting of uncontrolled hypertension and nephrotic-range proteinuria. However, his native kidney disease was never biopsy proven. The patient had only mild trace hematuria on his previous urinalysis, making IgA nephropathy an unlikely cause of his native disease and making de novo IgAN more likely. Another possibility is transmission of IgA deposits from the donor kidney. Latent mesangial IgA deposition in the donor kidneys has been described in up to 16% of Japanese allografts [10]. Without a donor renal biopsy, it is not possible to conclusively determine whether the IgA nephropathy in this patient was de novo or donor transmitted. However, several studies have shown that the IgA deposits disappear in few months after transplantation in repeated kidney biopsies [11,12]. Mesangial IgA deposits disappear when donor organs with silent IgAN are transplanted to recipients without IgAN [13]. These considerations suggest that the possibility of pathogenically significant transmission of IgA deposits from the donor kidney is unlikely. The patient, who was already on 100 mg losartan daily, was treated with 125 mg intravenous solumedrol daily for 3 days, followed by 20 mg oral prednisone tapered to 5 mg daily over the course of 2 months. MMF was increased from 1 g/d to 2 g/d. Consequently, his serum creatinine decreased from a peak of 2.4 mg/dL to 1.99 mg/dL. The protein concentration on the dipstick decreased from 2þ (100 mg/dL) to 1þ (30 mg/dL). His hematuria decreased from >50 to 4 red blood cells per high-power field. Renin-aldosterone system blockade has been shown in placebo-controlled trials to slow the progression of IgAN [14]. Steroids have been shown to slow the progression of IgAN, decrease the proteinuria, and improve 10-year renal survival [15]. MMF was not demonstrated to be superior to placebo in altering the progression of IgA nephropathy in a study done by Frisch et al [16]. However, one could argue that patients included in that study had advanced renal disease
KAMAL, SALVATORE, HARTONO ET AL
at the start (serum creatinine >2 mg/dL and 24-hour urine protein >2.7 g/d). Alternatively, Tang et al demonstrated that MMF can retard the progression of IgAN compared with placebo, and decrease the rate of decline of GFR in a study that involved 40 Asian patients with baseline eGFR of w50 mL/min/1.72 m2 and baseline 24-hour urine protein of 1.8 g/d [17]. CONCLUSION
De novo IgANy occurring in renal allografts may be a statistically underestimated disease entity. Two factors likely contribute to this underestimation. The first basis of this underestimation is the lack of native kidney biopsies demonstrating the conclusive diagnosis of the primary renal condition. For a variety of reasons, often the nature of a patients underlying renal impairment is a “presumptive” condition without conclusive tissue diagnosis. The second basis for the likely underestimation of de novo IgA nephropathy is the limited number of protocol allograft biopsies performed after transplantation. Considering that many cases of IgA nephropathy are subclinical, only the most severe cases trigger renal biopsies that disclose the presence of this condition. This case also highlights the contribution of multiple pathologic entities to declining renal function in a transplant allograft. This patient had evidence of concurrent diabetic nephropathy and IgAN. The presence of several coexisting disease states presented a therapeutic dilemma, because glucocorticoids, which have been demonstrated to slow progression of disease in IgAN, have the potential of worsening glycemic control and diabetic nephropathy. In our patient, the abrupt clinical presentation, combined with the predominance of biopsy findings suggesting significant active IgA nephropathy, led us to conclude that his recent clinical course was predominantly a manifestation of the IgAN. On this basis, we thought that the risk-benefit ratio favored treatment of the IgAN aggressively with the application of pulse steroids. In conclusion, IgAN is a relatively common entity in the post-transplantation setting and can coexist with diabetic nephropathy. Diagnosis requires a kidney biopsy with immunofluorescence studies, and treatment can be challenging, especially in the presence of diabetes and morbid obesity. REFERENCES [1] Yakupoglu U, Baranowska-Daca E, Rosen D, Barrios R, Suki WN, Truong LD. Post-transplant nephrotic syndrome: a comprehensive clinicopathologic study. Kidney Int 2004;65: 2360e70. [2] Ivanyi B. A primer on recurrent and de novo glomerulonephritis in renal allografts. Nat Clin Pract Nephrol 2008;4: 446e57. [3] d’Amico G. Natural history of idiopathic IgA nephropathy and factors predictive of disease outcome. Semin Nephrol 2004;24: 179e96. [4] Suzuki H, Fan R, Zhang Z, et al. Aberrantly glycosylated IgA1 in IgA nephropathy patients is recognized by IgG antibodies with restricted heterogeneity. J Clin Invest 2009;119:1668e77.
CONCOMITANCE OF IgA NEPHROPATHY AND DIABETIC NEPHROPATHY [5] Hariharan S, Peddi VR, Savin VJ, et al. Recurrent and de novo renal diseases after renal transplantation: a report from the renal allograft disease registry. Am J Kidney Dis 1998;31:928e31. [6] Floege J. Recurrent IgA nephropathy after renal transplantation. Semin Nephrol 2004;24:287e91. [7] Jeong HJ, Huh KH, Kim YS, Kim SI. IgA nephropathy in renal allografts-recurrence and graft dysfunction. Yonsei Med J 2004;45:1043e8. [8] Ponticelli C, Traversi L, Feliciani A, Cesana BM, Banfi G, Tarantino A. Kidney transplantation in patients with IgA mesangial glomerulonephritis. Kidney Int 2001;60:1948e54. [9] Nowack R, Birck R, van der Woude FJ. Mycophenolate mofetil for systemic vasculitis and IgA nephropathy. Lancet 1997;349:774. [10] Suzuki K, Honda K, Tanabe K, Toma H, Nihei H, Yamaguchi Y. Incidence of latent mesangial IgA deposition in renal allograft donors in Japan. Kidney Int 2003;63:2286e94. [11] Silva FG, Chander P, Pirani CL, Hardy MA. Disappearance of glomerular mesangial IgA deposits after renal allograft transplantation. Transplantation 1982;33:241e6.
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[12] Sanfilippo F, Croker BP, Bollinger RR. Fate of four cadaveric donor renal allografts with mesangial IgA deposits. Transplantation 1982;33:370e6. [13] Koselj M, Rott T, Kandus A, Vizjak A, Malovrh M. Donortransmitted IgA nephropathy: long-term follow-up of kidney donors and recipients. Transplant Proc 1997;29:3406e7. [14] Li PK, Leung CB, Chow KM, et al. Hong Kong study using valsartan in IgA nephropathy (HKVIN): a double-blind, randomized, placebo-controlled study. Am J Kidney Dis 2006;47: 751e60. [15] Pozzi C, Andrulli S, del Vecchio L, et al. Corticosteroid effectiveness in IgA nephropathy: long-term results of a randomized, controlled trial. J Am Soc Nephrol 2004;15:157e63. [16] Frisch G, Lin J, Rosenstock J, et al. Mycophenolate mofetil (MMF) vs placebo in patients with moderately advanced IgA nephropathy: a double-blind randomized controlled trial. Nephrol Dial Transplant 2005;20:2139e45. [17] Tang SC, Tang AW, Wong SS, Leung JC, Ho YW, Lai KN. Long-term study of mycophenolate mofetil treatment in IgA nephropathy. Kidney Int 2010;77:543e9.
New York Presbyterian HospitaleCornell Medical College, New York, New York; bThe Rogosin Institute, New York, New York
ABSTRACT Whereas diabetic nephropathy is the most common cause of end-stage renal disease (ESRD), IgA nephropathy is the most common glomerulonephritis in the world. We report a case of a kidney transplant recipient whose native renal disease was presumptive diabetic nephropathy. Five years after transplantation, the patient developed proteinuria, hematuria, and allograft dysfunction. Transplant biopsy revealed IgA nephropathy superimposed on diabetic nephropathy.
P
OST-TRANSPLANTATION proteinuria is common among transplant recipients. It has been estimated that w43% of renal transplant recipients develop proteinuria of >1 g/d [1]. It is most commonly caused by chronic allograft injury with glomerulosclerosis (with or without transplant glomerulopathy). Post-transplantation glomerulonephritis, either recurrent or de novo, also is an important cause of post-transplantation proteinuria with or without allograft dysfunction. However, the exact prevalence of post-transplantation glomerulonephritis is not well determined. In a transplant recipient, urinalysis may not be performed routinely and proteinuria can be missed. Even if proteinuria is detected, it might be evaluated differently than the one that occurs in the native kidney. Additionally, immunofluorescence and electron microscopy might not be routinely performed on the biopsy specimen [2]. IgA nephropathy (IgAN) is the most common glomerulonephritis in the world. It is most common in Asians. It is characterized by dominant IgA deposits by immunofluorescence in the mesangial areas [3]. The deposited IgA immunoglobulins have a poorly O-galactosylated hinge region, which increases their tendency to aggregate and form antigen-antibody complexes with IgG directed against the hinge region [4]. IgAN is known for its tendency to recur in the allograft after renal transplantation. The rate of recurrence and the effect it has on allograft survival are difficult to determine owing to a lack of prospective studies involving protocol biopsies. We herein describe a case of IgAN detected in a renal transplant recipient whose original renal disease was presumably secondary to diabetic nephropathy.
CASE REPORT We are reporting a case of a 68-year-old white man with longstanding poorly controlled diabetes, diabetic retinopathy, hypertension with left ventricular hypertrophy and diastolic dysfunction, coronary artery disease, and morbid obesity, who had chronic kidney disease with nephrotic range proteinuria that ultimately progressed to end-stage renal disease (ESRD). The patient’s clinical presentation, which included progressive proteinuric renal impairment in the setting of diabetes with advanced end-organ sequelae, such as retinopathy, without any atypical features for alternative diagnoses, strongly suggested diabetic nephropathy as the etiology for his renal disease. He required hemodialysis for 1 year, followed by a 6eHLA antigen mismatch renal transplant from an expanded-criteria donor, with thymoglobulin induction. His transplant course was notable for delayed graft function requiring dialysis support, but then he recovered normal renal function. His post-transplantation medications included tacrolimus and mycophenolate. He did not receive prednisone maintenance. Five years after the transplantation, his serum creatinine started to increase, and he developed new-onset subnephroticrange proteinuria (protein/creatinine ratio, 1 g/g on spot urine) along with microscopic hematuria. At the same time, he reported frothy urine and leg swelling, but no gross hematuria. His blood pressure was 128/70 mm Hg, and his physical examination was notable for 1þ pitting edema involving both legs. His family history was significant for diabetes, but there was no family history of renal disease. Serum creatinine increased from a baseline of 1 mg/ dL to 2 mg/dL, prompting a renal biopsy. The renal biopsy was notable for mild class II diabetic nephropathy, evidenced by mesangial expansion and glomerular basement membrane *Address correspondence to Alan Perlman, MD, Rogosin Institute, New York Presbyterian HospitaleCornell Medical College, 505 E. 70th Street, HT- 226, New York, New York, 10021. E-mail: [email protected]
0041-1345/14 http://dx.doi.org/10.1016/j.transproceed.2014.06.048
ª 2014 by Elsevier Inc. All rights reserved. 360 Park Avenue South, New York, NY 10010-1710
2396
Transplantation Proceedings, 46, 2396e2399 (2014)
CONCOMITANCE OF IgA NEPHROPATHY AND DIABETIC NEPHROPATHY
2397
Fig 1. Glomerulus with mild expansion of mesangial matrix and minimal mesangial hypercellularity (H&E, 40x).
thickening (Figs 1 and 3). Immunofluorescence showed 3þ granular IgA and 3þ C3 deposition, mainly along the glomerular mesangial areas in a global distribution consistent with IgA nephropathy (Fig 2). C4d staining was negative and there was no evidence of cellular or antibody mediated rejection. These findings were highly consistent with IgA nephropathy.
DISCUSSION
The prevalence of post-transplantation glomerulonephritis is not exactly known. Reasons include the different approaches that transplant centers take toward the evaluation of proteinuria and allograft dysfunction that occur in the 12 months after transplantation. Proteinuria or increased creatinine are often attributed to what was previously recognized as “chronic allograft nephropathy” or nonspecific interstitial fibrosis and tubular atrophy, and urinalysis to detect hematuria or active urine sediment may
Fig 2. Immunofluorescence microscopy revealing granular 3þ staining of the mesangium for anti-IgA. (IgA, 40x).
Fig 3. Electron microscopic image showing irregular thickening of the glomerular basement membranes as well as endothelial cell swelling, subendothelial widening with focal new basement membrane formation. Small paramesangial electron dense deposits are also present. (EM, 6000x).
not be routinely performed. Furthermore, it is even harder to differentiate between de novo or recurrent glomerulonephritis, because the kidney recipient’s native disease is frequently not biopsy proven. Glomerulonephritis identified in the allograft may be due also to an unidentified donor disease, and biopsies of the donor kidney are rarely done at the time of implantation. Prevalence of posttransplantation glomerulonephritis ranges from 3% to 13% according to different reports [5]. In a study of 74 renal transplant recipients with post-transplantation nephrotic syndrome, de novo glomerular diseases accounted for 24% of the cases and recurrent glomerular diseases for 20%. Among the 15 cases of recurrent glomerular diseases, 6 cases were due to IgAN, and 2 patients had IgAN among the 18 cases of “de novo” glomerular diseases. In 9 cases the native kidney disease was unknown, and 2 of these 9 patients had IgAN. Of note, in 10% of the patients, the original kidney disease was secondary to diabetic nephropathy [1]. IgAN can lead to ESRD in 25% of cases [6]. IgAN is known for its high recurrence rate after transplantation. The rate of recurrence ranges from 13% to 60% and varies between different series depending on the timing of the biopsy and on whether it is a clinical or histologic recurrence [7]. The rate of histologic recurrence can be as high as 50%e60% [6]. Clinical recurrent IgAN is characterized by proteinuria of >500 mg/d, microscopic hematuria, and
2398
mesangioproliferative glomerulonephritis on kidney biopsy. Recurrent IgAN is not a benign condition; it has been demonstrated to progress to graft dysfunction and loss of graft in up to 16% of cases [2]. However, the incidence of graft dysfunction in recurrent IgAN varies from one report to another. In a series of 106 patients with IgAN, Ponticelli et al found a biopsy-proven recurrence rate of 35%, and the recurrence did not affect the 10-year graft survival and was not associated with increased risk of graft failure [8]. IgAN recurrence does not appear to be preventable by immunosuppressive drugs, including mycophenolate (MMF) [8]. Although MMF has been shown to modify the course of the disease [9], this was not proven in a 3-year randomized controlled trial of MMF in IgAN that showed a lack of efficacy of MMF on renal function or proteinuria [1]. The present patient’s underlying cause of ESRD was presumably diabetic nephropathy, given the history of uncontrolled diabetes with definitive end-organ sequelae of diabetic retinopathy, in the setting of uncontrolled hypertension and nephrotic-range proteinuria. However, his native kidney disease was never biopsy proven. The patient had only mild trace hematuria on his previous urinalysis, making IgA nephropathy an unlikely cause of his native disease and making de novo IgAN more likely. Another possibility is transmission of IgA deposits from the donor kidney. Latent mesangial IgA deposition in the donor kidneys has been described in up to 16% of Japanese allografts [10]. Without a donor renal biopsy, it is not possible to conclusively determine whether the IgA nephropathy in this patient was de novo or donor transmitted. However, several studies have shown that the IgA deposits disappear in few months after transplantation in repeated kidney biopsies [11,12]. Mesangial IgA deposits disappear when donor organs with silent IgAN are transplanted to recipients without IgAN [13]. These considerations suggest that the possibility of pathogenically significant transmission of IgA deposits from the donor kidney is unlikely. The patient, who was already on 100 mg losartan daily, was treated with 125 mg intravenous solumedrol daily for 3 days, followed by 20 mg oral prednisone tapered to 5 mg daily over the course of 2 months. MMF was increased from 1 g/d to 2 g/d. Consequently, his serum creatinine decreased from a peak of 2.4 mg/dL to 1.99 mg/dL. The protein concentration on the dipstick decreased from 2þ (100 mg/dL) to 1þ (30 mg/dL). His hematuria decreased from >50 to 4 red blood cells per high-power field. Renin-aldosterone system blockade has been shown in placebo-controlled trials to slow the progression of IgAN [14]. Steroids have been shown to slow the progression of IgAN, decrease the proteinuria, and improve 10-year renal survival [15]. MMF was not demonstrated to be superior to placebo in altering the progression of IgA nephropathy in a study done by Frisch et al [16]. However, one could argue that patients included in that study had advanced renal disease
KAMAL, SALVATORE, HARTONO ET AL
at the start (serum creatinine >2 mg/dL and 24-hour urine protein >2.7 g/d). Alternatively, Tang et al demonstrated that MMF can retard the progression of IgAN compared with placebo, and decrease the rate of decline of GFR in a study that involved 40 Asian patients with baseline eGFR of w50 mL/min/1.72 m2 and baseline 24-hour urine protein of 1.8 g/d [17]. CONCLUSION
De novo IgANy occurring in renal allografts may be a statistically underestimated disease entity. Two factors likely contribute to this underestimation. The first basis of this underestimation is the lack of native kidney biopsies demonstrating the conclusive diagnosis of the primary renal condition. For a variety of reasons, often the nature of a patients underlying renal impairment is a “presumptive” condition without conclusive tissue diagnosis. The second basis for the likely underestimation of de novo IgA nephropathy is the limited number of protocol allograft biopsies performed after transplantation. Considering that many cases of IgA nephropathy are subclinical, only the most severe cases trigger renal biopsies that disclose the presence of this condition. This case also highlights the contribution of multiple pathologic entities to declining renal function in a transplant allograft. This patient had evidence of concurrent diabetic nephropathy and IgAN. The presence of several coexisting disease states presented a therapeutic dilemma, because glucocorticoids, which have been demonstrated to slow progression of disease in IgAN, have the potential of worsening glycemic control and diabetic nephropathy. In our patient, the abrupt clinical presentation, combined with the predominance of biopsy findings suggesting significant active IgA nephropathy, led us to conclude that his recent clinical course was predominantly a manifestation of the IgAN. On this basis, we thought that the risk-benefit ratio favored treatment of the IgAN aggressively with the application of pulse steroids. In conclusion, IgAN is a relatively common entity in the post-transplantation setting and can coexist with diabetic nephropathy. Diagnosis requires a kidney biopsy with immunofluorescence studies, and treatment can be challenging, especially in the presence of diabetes and morbid obesity. REFERENCES [1] Yakupoglu U, Baranowska-Daca E, Rosen D, Barrios R, Suki WN, Truong LD. Post-transplant nephrotic syndrome: a comprehensive clinicopathologic study. Kidney Int 2004;65: 2360e70. [2] Ivanyi B. A primer on recurrent and de novo glomerulonephritis in renal allografts. Nat Clin Pract Nephrol 2008;4: 446e57. [3] d’Amico G. Natural history of idiopathic IgA nephropathy and factors predictive of disease outcome. Semin Nephrol 2004;24: 179e96. [4] Suzuki H, Fan R, Zhang Z, et al. Aberrantly glycosylated IgA1 in IgA nephropathy patients is recognized by IgG antibodies with restricted heterogeneity. J Clin Invest 2009;119:1668e77.
CONCOMITANCE OF IgA NEPHROPATHY AND DIABETIC NEPHROPATHY [5] Hariharan S, Peddi VR, Savin VJ, et al. Recurrent and de novo renal diseases after renal transplantation: a report from the renal allograft disease registry. Am J Kidney Dis 1998;31:928e31. [6] Floege J. Recurrent IgA nephropathy after renal transplantation. Semin Nephrol 2004;24:287e91. [7] Jeong HJ, Huh KH, Kim YS, Kim SI. IgA nephropathy in renal allografts-recurrence and graft dysfunction. Yonsei Med J 2004;45:1043e8. [8] Ponticelli C, Traversi L, Feliciani A, Cesana BM, Banfi G, Tarantino A. Kidney transplantation in patients with IgA mesangial glomerulonephritis. Kidney Int 2001;60:1948e54. [9] Nowack R, Birck R, van der Woude FJ. Mycophenolate mofetil for systemic vasculitis and IgA nephropathy. Lancet 1997;349:774. [10] Suzuki K, Honda K, Tanabe K, Toma H, Nihei H, Yamaguchi Y. Incidence of latent mesangial IgA deposition in renal allograft donors in Japan. Kidney Int 2003;63:2286e94. [11] Silva FG, Chander P, Pirani CL, Hardy MA. Disappearance of glomerular mesangial IgA deposits after renal allograft transplantation. Transplantation 1982;33:241e6.
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[12] Sanfilippo F, Croker BP, Bollinger RR. Fate of four cadaveric donor renal allografts with mesangial IgA deposits. Transplantation 1982;33:370e6. [13] Koselj M, Rott T, Kandus A, Vizjak A, Malovrh M. Donortransmitted IgA nephropathy: long-term follow-up of kidney donors and recipients. Transplant Proc 1997;29:3406e7. [14] Li PK, Leung CB, Chow KM, et al. Hong Kong study using valsartan in IgA nephropathy (HKVIN): a double-blind, randomized, placebo-controlled study. Am J Kidney Dis 2006;47: 751e60. [15] Pozzi C, Andrulli S, del Vecchio L, et al. Corticosteroid effectiveness in IgA nephropathy: long-term results of a randomized, controlled trial. J Am Soc Nephrol 2004;15:157e63. [16] Frisch G, Lin J, Rosenstock J, et al. Mycophenolate mofetil (MMF) vs placebo in patients with moderately advanced IgA nephropathy: a double-blind randomized controlled trial. Nephrol Dial Transplant 2005;20:2139e45. [17] Tang SC, Tang AW, Wong SS, Leung JC, Ho YW, Lai KN. Long-term study of mycophenolate mofetil treatment in IgA nephropathy. Kidney Int 2010;77:543e9.