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Recovery of Native Renal Function After Kidney Transplantation
Recovery of Native Renal Function After Kidney Transplantation P. Hidalgo, T. Jiménez, L. Blanca, C. Cobelo, D. Burgos, I. Garcia, and D. Hernández ABSTRACT IgA nephropathy is the most frequently occurring glomerulonephritis in the developed world. It is treated in the terminal phase via dialysis and transplantation. Posttransplantation recurrence is common, but evolves slowly. Herein, recovery of native kidney function 10 years after transplantation in a patient with IgA glomerulonephritis is described, and the potential effect of immunosuppression therapy, in particular with mycophenolate mofetil, is discussed. HE MOST FREQUENTLY OCCURRING glomerulonephritis in the developed world, IgA nephropathy, is characterized by diffuse, predominantly mesangial deposits of IgA in the glomeruli. Its evolution is relatively benign, and can lead slowly to chronic renal failure in as many as 50% of affected patients. The disease is treated in the terminal phase via dialysis and transplantation. Posttransplantation recurrence is common, but evolves slowly. To our knowledge, no data have been published about the course of IgA glomerulonephritis in native kidneys after transplantation. Herein, we describe recovery of native kidney function after transplantation in a patient with IgA glomerulonephritis.1– 6
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CASE REPORT A 42-year-old woman was diagnosed in February 1995 (at the age of 30) with nephrotic syndrome, with proteinuria (3.7 g per 24 hours), total protein, 4.3 g; serum albumin, 2.5 g; and low-density lipoprotein cholesterol, 245 mg/dL. In addition, she had hypertension, persistent hematuria, and plasma creatinine concentration of 1.3 mg/dL (Modification of Diet in Renal Disease–7 [MDRD-7], 50.45 mL/min). A renal biopsy specimen obtained 3 months after the diagnosis demonstrated mesangial IgA glomerulonephropathy with a proliferative diffuse endocapillary histologic pattern and fibrocellular crescents in 30% of the glomeruli (Fig 1). Renal function worsened rapidly over 1 year, with plasma creatinine concentration of 3.8 mg/dL (MDRD-7, 15 mL/min), residual diuresis of 1000 mL, and persistent microhematuria, and hemodialysis therapy was initiated in August 1996. After receiving hemodialysis therapy for 9 months, the patient underwent cadaver kidney transplantation. Cold ischemia time was 35 hours. Initial immunosuppression therapy was with polyclonal antibodies, steroids, mycophenolate mofetil (MMF), and cyclosporine (CsA) (day 4). The postoperative course was uneventful. Steroid therapy was discontinued at 2 years posttransplantation. Because the patient desired to become pregnant, only CsA was administered from 2004 to 2008. During this time, the patient had 2 miscarriages, and a cesarean delivery at term in 2007. Renal function remained stable (plasma creatinine concentration, 1.5
mg/dL), lipids and blood pressure were controlled without medication, and urinary sediment was normal. Doppler ultrasound performed at 6 years posttransplantation demonstrated both native kidneys of 8 cm, and the kidney graft with good corticomedullary differentiation without dilatation of the excretory tract, as well as conserved flow and normal diastole (Fig 2). Doppler ultrasound performed at 10 years posttransplantation (during week 13 of the third pregnancy) demonstrated normal characteristics of the native kidneys without visualization of the renal graft. Renal function was stable (plasma creatinine concentration, 1.5 mg/dL), 24-hour proteinuria of 0.5 g, and good control of blood pressure. Lack of visualization of the graft was interpreted as being secondary to migration during uterine growth. Ultrasonography performed again, after the cesarean delivery, and the kidney graft was still not visible. Emergency computed tomography without contrast medium demonstrated minimal scarring of the right iliac fossa. Renal function was stable (plasma creatinine concentration, 1.6 mg/dL), with proteinuria, 0.46 g per 24 hours, no hematuria, and blood pressure controlled without antihypertension drugs. The imaging study was extended to evaluate the structure and function of both native kidneys and the graft. Computed tomography with contrast medium demonstrated a left kidney of 9.18 cm with a 2.44-cm cortex, and a right kidney of 7.5 cm with a 2.24-cm cortex. The kidney graft was reduced in size (72 mm in longitudinal axis), with marked cortical atrophy and uptake of contrast medium. In the excretory phase, the native kidneys demonstrated bilateral symmetric elimination. The bladder contained contrast medium. Mild contrast medium concentration was present in the renal graft excretory system (Fig 3). Renograms demonstrated native kidneys with low levels of uptake throughout the study, and slight pyelocalyceal retention that emptied at the end of the study. The transplanted kidney was reduced to a remnant with minimal functional capacity (Fig 4). From the Nephrology Service, Carlos Haya University Hospital, Malaga, Spain. Address reprint requests to Pilar Hidalgo, C/Parménides 11, Bldg 2-5B, 29010 Malaga, Spain. E-mail: [email protected]
© 2010 Published by Elsevier Inc. 360 Park Avenue South, New York, NY 10010-1710
0041-1345/–see front matter doi:10.1016/j.transproceed.2010.05.126
Transplantation Proceedings, 42, 3137–3140 (2010)
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Fig 1. A, Histologic analysis demonstrates diffuse endocapillary proliferation and fibrocellular crescents (active lesions) (periodic acid–Schiff stain). B, Diffuse endocapillary proliferation (periodic acid–Schiff and Masson stains). C, Immunofluorescence study shows diffuse IgA deposits in a parietal pattern.
At scintigraphy, native kidney function curves demonstrated slowing of the excretory phase, with somewhat lesser function in the left kidney. The curve obtained in the transplanted kidney demonstrated low uptake, compatible with chronic renal failure with almost no function. Total function in the native kidneys was 93.8%, and in the transplanted kidney was only 6.12%. Currently, the patient has stable renal function (plasma creatinine concentration, 1.4 mg/dL), proteinuria, 0.56 g per 24 hours; normal sediment, and normotension without antihypertension therapy. The immunosuppression therapy was gradually completely
withdrawn, and the patient was transferred to the general nephrology service.
DISCUSSION
This case report describes partial recovery of the native kidneys in a patient who underwent transplantation in 1997. When the graft function was lost is not known exactly, probably due to a silent interstitial fibrosis and tubular atrophy, although the patient had only proteinuria during
Fig 2. Kidney graft with good corticomedullary differentiation. Doppler ultrasound study demonstrates conserved flow and normal diastole.
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Fig 3. Computed tomography with contrast medium. Left kidney is 9.18 cm in greatest diameter, with 2.44-cm cortex, and right kidney is 7.5 cm, with 2.24-cm cortex. Kidney graft is reduced in size (72 mm in longitudinal axis), and demonstrates marked cortical atrophy with uptake of contrast medium. In the excretory phase, native kidneys exhibit bilateral symmetric elimination. Bladder contains contrast medium. Mild contrast concentration is seen in the renal graft excretory system.
pregnancy. Alternatively, there may have been graft vessel compression by the gravid uterus, although this has not been described previously.7 Although initially it was believed that IgA nephropathy has a benign course, it is now known that slow progression to end-stage renal failure occurs in as many as 50% of affected patients. The remaining patients have persistent hematuria or proteinuria. Spontaneous clinical remission has been reported in 5% to 30% of cases.8,9 A number of predictors have been linked to spontaneous remission, including less than 30% of sclerotic glomeruli at biopsy, presence of residual diuresis, proteinuria less than 500 to 1000 mg per 24 hours, no hypertension, and plasma creatinine concentration less than 2.5 mg/dL at diagnosis.10 In our patient, we considered the possibility of spontaneous remission of disease throughout the transplantation period because at disease diagnosis the data were favorable: plasma creatinine concentration of 1.3 mg/dL, residual diuresis, and no chronic lesion at histologic analysis.
The pathophysiology of IgA nephropathy is not yet well established, and treatment is uncertain. General nonspecific treatment is given in an attempt to slow progression of renal disease, and includes strict control of blood pressure, use of angiotensin-converting enzyme inhibitors and angiotensin-receptor blockers in the presence of proteinuria, and statins in patients with increased cholesterol concentrations. Immunosuppression therapy in administered in patients at high risk of progression to end-stage renal disease. Thus, patients with isolated hematuria, no or minimal proteinuria, and normal glomerular filtration rate should receive only general treatment. Patients with persistent proteinuria or normal or slightly decreased glomerular filtration rate should receive general treatment plus fish oil. Patients with rapidly progressive glomerulonephritis or persistent proteinuria despite treatment with angiotensinconverting enzyme inhibitors or angiotensin-receptor blockers, and those with increased creatinine concentration or a renal biopsy specimen that exhibits severe histologic signs (not
Fig 4. At renography, native kidneys demonstrated low levels of uptake throughout the study, with slight pyelocalyceal retention that emptied at the end of the study. The transplanted kidney was reduced to a remnant with minimal functional capacity.
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compatible with chronic disease) may be candidates for immunosuppression therapy.11–13 The role of immunosuppression therapy in IgA glomerulonephropathy is unclear. Among several regimens used, the most common include isolated glucocorticoid or other immunosuppressant agents. No conclusive studies exist, and the results are contradictory. Most studies have included small samples and short follow-up. The usual therapy is with prednisone and cyclophosphamide in severe cases.14 Our patient received initial immunosuppression with polyclonal antibodies, steroids, MMF, and CsA. Steroid therapy was discontinued at 2 years posttransplantation, and CsA monotherapy was continued for 4 years after transplantation. We considered the possibility of the role of immunosuppression with MMF and CsA in the partial recovery of renal function of the native kidneys. In 1987, Lai et al15 published a small 12-week study that demonstrated that CsA vs placebo in patients with IgA causes a reduction in proteinuria. Studies that have demonstrated decreased proteinuria in IgA nephropathy treated with CsA (although no study has shown improvement in renal function) included only a few patients and short follow-up.15 Moreover, MMF is an immunosuppression agent that acts by suppressing formation of antibodies by B cells by preventing de novo synthesis of purines. This agent may be effective in reducing proteinuria in several glomerular diseases including IgA glomerulonephritis. In patients with IgA nephropathy and advanced renal impairment, MMF does not decrease proteinuria. However, in the early stages of the disease (no histologic evidence of chronicity), MMF has shown a significant decrease in proteinuria. Because proteinuria is a marker of kidney damage and a risk factor for development of kidney failure, short-term MMF therapy may decrease proteinuria, and in the long term, may be renoprotective in mild to moderate IgA nephropathy.16,17 REFERENCES 1. Hotta O, Furuta T, Chiba S, et al: Regression of IgA nephropathy: a repeat biopsy study. Am J Kidney Dis 39:493, 2002
HIDALGO, JIMÉNEZ, BLANCA ET AL 2. Ibels LS, Gyory AZ: IgA nephropathy: analysis of the natural history, important factors in the progression of renal disease, and a review of the literature. Medicine (Baltimore) 73:79, 1994 3. Nozawa R, Suzuki J, Takahashi A, et al: Clinicopathological features and the prognosis of IgA nephropathy in Japanese children on long-term observation. Clin Nephrol 64:171, 2005 4. Lau KK, Gaber LW, Delos Santos NM, et al: Pediatric IgA nephropathy: clinical features at presentation and outcome for African-Americans and Caucasians. Clin Nephrol 62:167, 2004 5. Bartosik LP, Lajoie G, Sugar L, et al: Predicting progression in IgA nephropathy. Am J Kidney Dis 38:728, 2001 6. Histologic subclassification of IgA nephropathy: a clinicopathologic study of 244 cases. Am J Kidney Dis 29:829, 1997 7. Pallardó LM, Crespo JF: Embarazo y trasplante renal: luces y sombras. Nefrología 28:148, 2008 8. Praga M, Gutierrez-Millet V, Navas JJ, et al: Acute worsening of renal function during episodes of macroscopic hematuria in IgA nephropathy. Kidney Int 28:69, 1985 9. Reich HN, Troyanov S, Scholey JW, et al: Remission of proteinuria improves prognosis in IgA nephropathy. J Am Soc Nephrol 18:3177, 2007 10. Appel GB, Waldman M: The IgA nephropathy treatment dilemma. Kidney Int 69:1939, 2006 11. Ballardie FW, Roberts IS: Controlled prospective trial of prednisolone and cytotoxics in progressive IgA nephropathy. J Am Soc Nephrol 13:142, 2002 12. Donadio JV, Grande JP: The role of fish oil/omega-3 fatty acid in the treatment of IgA nephropathy. Semin Nephrol 24:225, 2004 13. Kim PK, Kim KS, Pai KS, et al: Long-term results of cyclosporine-induced remission of relapsing nephrotic syndrome in children. Yonsei Med J 38:307, 1997 14. Descoeudres B, Giannini O, Aschwanden M, et al: Silent recovery of native kidney function after transplantation in a patient with membranous nephropathy. Nephrol Dial Transplant 24:1345, 2009 15. Lai KN, Lai FM, Li PK, et al: Cyclosporin treatment of IgA nephropathy: a short term controlled trial. J Br Med J (Clin Res Ed) 295:1165, 1987 16. Tan CH, Lo PT, Yang WS, et al: Mycophenolate mofetil in the treatment of IgA nephropathy: a systematic review. Singapore Med J 49:780, 2008 17. Xu G, Tu W, Jiang D, et al: Mycophenolate mofetil treatment for IgA nephropathy: a meta-analysis. Am J Nephrol 29:362, 2009
T
CASE REPORT A 42-year-old woman was diagnosed in February 1995 (at the age of 30) with nephrotic syndrome, with proteinuria (3.7 g per 24 hours), total protein, 4.3 g; serum albumin, 2.5 g; and low-density lipoprotein cholesterol, 245 mg/dL. In addition, she had hypertension, persistent hematuria, and plasma creatinine concentration of 1.3 mg/dL (Modification of Diet in Renal Disease–7 [MDRD-7], 50.45 mL/min). A renal biopsy specimen obtained 3 months after the diagnosis demonstrated mesangial IgA glomerulonephropathy with a proliferative diffuse endocapillary histologic pattern and fibrocellular crescents in 30% of the glomeruli (Fig 1). Renal function worsened rapidly over 1 year, with plasma creatinine concentration of 3.8 mg/dL (MDRD-7, 15 mL/min), residual diuresis of 1000 mL, and persistent microhematuria, and hemodialysis therapy was initiated in August 1996. After receiving hemodialysis therapy for 9 months, the patient underwent cadaver kidney transplantation. Cold ischemia time was 35 hours. Initial immunosuppression therapy was with polyclonal antibodies, steroids, mycophenolate mofetil (MMF), and cyclosporine (CsA) (day 4). The postoperative course was uneventful. Steroid therapy was discontinued at 2 years posttransplantation. Because the patient desired to become pregnant, only CsA was administered from 2004 to 2008. During this time, the patient had 2 miscarriages, and a cesarean delivery at term in 2007. Renal function remained stable (plasma creatinine concentration, 1.5
mg/dL), lipids and blood pressure were controlled without medication, and urinary sediment was normal. Doppler ultrasound performed at 6 years posttransplantation demonstrated both native kidneys of 8 cm, and the kidney graft with good corticomedullary differentiation without dilatation of the excretory tract, as well as conserved flow and normal diastole (Fig 2). Doppler ultrasound performed at 10 years posttransplantation (during week 13 of the third pregnancy) demonstrated normal characteristics of the native kidneys without visualization of the renal graft. Renal function was stable (plasma creatinine concentration, 1.5 mg/dL), 24-hour proteinuria of 0.5 g, and good control of blood pressure. Lack of visualization of the graft was interpreted as being secondary to migration during uterine growth. Ultrasonography performed again, after the cesarean delivery, and the kidney graft was still not visible. Emergency computed tomography without contrast medium demonstrated minimal scarring of the right iliac fossa. Renal function was stable (plasma creatinine concentration, 1.6 mg/dL), with proteinuria, 0.46 g per 24 hours, no hematuria, and blood pressure controlled without antihypertension drugs. The imaging study was extended to evaluate the structure and function of both native kidneys and the graft. Computed tomography with contrast medium demonstrated a left kidney of 9.18 cm with a 2.44-cm cortex, and a right kidney of 7.5 cm with a 2.24-cm cortex. The kidney graft was reduced in size (72 mm in longitudinal axis), with marked cortical atrophy and uptake of contrast medium. In the excretory phase, the native kidneys demonstrated bilateral symmetric elimination. The bladder contained contrast medium. Mild contrast medium concentration was present in the renal graft excretory system (Fig 3). Renograms demonstrated native kidneys with low levels of uptake throughout the study, and slight pyelocalyceal retention that emptied at the end of the study. The transplanted kidney was reduced to a remnant with minimal functional capacity (Fig 4). From the Nephrology Service, Carlos Haya University Hospital, Malaga, Spain. Address reprint requests to Pilar Hidalgo, C/Parménides 11, Bldg 2-5B, 29010 Malaga, Spain. E-mail: [email protected]
© 2010 Published by Elsevier Inc. 360 Park Avenue South, New York, NY 10010-1710
0041-1345/–see front matter doi:10.1016/j.transproceed.2010.05.126
Transplantation Proceedings, 42, 3137–3140 (2010)
3137
3138
HIDALGO, JIMÉNEZ, BLANCA ET AL
Fig 1. A, Histologic analysis demonstrates diffuse endocapillary proliferation and fibrocellular crescents (active lesions) (periodic acid–Schiff stain). B, Diffuse endocapillary proliferation (periodic acid–Schiff and Masson stains). C, Immunofluorescence study shows diffuse IgA deposits in a parietal pattern.
At scintigraphy, native kidney function curves demonstrated slowing of the excretory phase, with somewhat lesser function in the left kidney. The curve obtained in the transplanted kidney demonstrated low uptake, compatible with chronic renal failure with almost no function. Total function in the native kidneys was 93.8%, and in the transplanted kidney was only 6.12%. Currently, the patient has stable renal function (plasma creatinine concentration, 1.4 mg/dL), proteinuria, 0.56 g per 24 hours; normal sediment, and normotension without antihypertension therapy. The immunosuppression therapy was gradually completely
withdrawn, and the patient was transferred to the general nephrology service.
DISCUSSION
This case report describes partial recovery of the native kidneys in a patient who underwent transplantation in 1997. When the graft function was lost is not known exactly, probably due to a silent interstitial fibrosis and tubular atrophy, although the patient had only proteinuria during
Fig 2. Kidney graft with good corticomedullary differentiation. Doppler ultrasound study demonstrates conserved flow and normal diastole.
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Fig 3. Computed tomography with contrast medium. Left kidney is 9.18 cm in greatest diameter, with 2.44-cm cortex, and right kidney is 7.5 cm, with 2.24-cm cortex. Kidney graft is reduced in size (72 mm in longitudinal axis), and demonstrates marked cortical atrophy with uptake of contrast medium. In the excretory phase, native kidneys exhibit bilateral symmetric elimination. Bladder contains contrast medium. Mild contrast concentration is seen in the renal graft excretory system.
pregnancy. Alternatively, there may have been graft vessel compression by the gravid uterus, although this has not been described previously.7 Although initially it was believed that IgA nephropathy has a benign course, it is now known that slow progression to end-stage renal failure occurs in as many as 50% of affected patients. The remaining patients have persistent hematuria or proteinuria. Spontaneous clinical remission has been reported in 5% to 30% of cases.8,9 A number of predictors have been linked to spontaneous remission, including less than 30% of sclerotic glomeruli at biopsy, presence of residual diuresis, proteinuria less than 500 to 1000 mg per 24 hours, no hypertension, and plasma creatinine concentration less than 2.5 mg/dL at diagnosis.10 In our patient, we considered the possibility of spontaneous remission of disease throughout the transplantation period because at disease diagnosis the data were favorable: plasma creatinine concentration of 1.3 mg/dL, residual diuresis, and no chronic lesion at histologic analysis.
The pathophysiology of IgA nephropathy is not yet well established, and treatment is uncertain. General nonspecific treatment is given in an attempt to slow progression of renal disease, and includes strict control of blood pressure, use of angiotensin-converting enzyme inhibitors and angiotensin-receptor blockers in the presence of proteinuria, and statins in patients with increased cholesterol concentrations. Immunosuppression therapy in administered in patients at high risk of progression to end-stage renal disease. Thus, patients with isolated hematuria, no or minimal proteinuria, and normal glomerular filtration rate should receive only general treatment. Patients with persistent proteinuria or normal or slightly decreased glomerular filtration rate should receive general treatment plus fish oil. Patients with rapidly progressive glomerulonephritis or persistent proteinuria despite treatment with angiotensinconverting enzyme inhibitors or angiotensin-receptor blockers, and those with increased creatinine concentration or a renal biopsy specimen that exhibits severe histologic signs (not
Fig 4. At renography, native kidneys demonstrated low levels of uptake throughout the study, with slight pyelocalyceal retention that emptied at the end of the study. The transplanted kidney was reduced to a remnant with minimal functional capacity.
3140
compatible with chronic disease) may be candidates for immunosuppression therapy.11–13 The role of immunosuppression therapy in IgA glomerulonephropathy is unclear. Among several regimens used, the most common include isolated glucocorticoid or other immunosuppressant agents. No conclusive studies exist, and the results are contradictory. Most studies have included small samples and short follow-up. The usual therapy is with prednisone and cyclophosphamide in severe cases.14 Our patient received initial immunosuppression with polyclonal antibodies, steroids, MMF, and CsA. Steroid therapy was discontinued at 2 years posttransplantation, and CsA monotherapy was continued for 4 years after transplantation. We considered the possibility of the role of immunosuppression with MMF and CsA in the partial recovery of renal function of the native kidneys. In 1987, Lai et al15 published a small 12-week study that demonstrated that CsA vs placebo in patients with IgA causes a reduction in proteinuria. Studies that have demonstrated decreased proteinuria in IgA nephropathy treated with CsA (although no study has shown improvement in renal function) included only a few patients and short follow-up.15 Moreover, MMF is an immunosuppression agent that acts by suppressing formation of antibodies by B cells by preventing de novo synthesis of purines. This agent may be effective in reducing proteinuria in several glomerular diseases including IgA glomerulonephritis. In patients with IgA nephropathy and advanced renal impairment, MMF does not decrease proteinuria. However, in the early stages of the disease (no histologic evidence of chronicity), MMF has shown a significant decrease in proteinuria. Because proteinuria is a marker of kidney damage and a risk factor for development of kidney failure, short-term MMF therapy may decrease proteinuria, and in the long term, may be renoprotective in mild to moderate IgA nephropathy.16,17 REFERENCES 1. Hotta O, Furuta T, Chiba S, et al: Regression of IgA nephropathy: a repeat biopsy study. Am J Kidney Dis 39:493, 2002
HIDALGO, JIMÉNEZ, BLANCA ET AL 2. Ibels LS, Gyory AZ: IgA nephropathy: analysis of the natural history, important factors in the progression of renal disease, and a review of the literature. Medicine (Baltimore) 73:79, 1994 3. Nozawa R, Suzuki J, Takahashi A, et al: Clinicopathological features and the prognosis of IgA nephropathy in Japanese children on long-term observation. Clin Nephrol 64:171, 2005 4. Lau KK, Gaber LW, Delos Santos NM, et al: Pediatric IgA nephropathy: clinical features at presentation and outcome for African-Americans and Caucasians. Clin Nephrol 62:167, 2004 5. Bartosik LP, Lajoie G, Sugar L, et al: Predicting progression in IgA nephropathy. Am J Kidney Dis 38:728, 2001 6. Histologic subclassification of IgA nephropathy: a clinicopathologic study of 244 cases. Am J Kidney Dis 29:829, 1997 7. Pallardó LM, Crespo JF: Embarazo y trasplante renal: luces y sombras. Nefrología 28:148, 2008 8. Praga M, Gutierrez-Millet V, Navas JJ, et al: Acute worsening of renal function during episodes of macroscopic hematuria in IgA nephropathy. Kidney Int 28:69, 1985 9. Reich HN, Troyanov S, Scholey JW, et al: Remission of proteinuria improves prognosis in IgA nephropathy. J Am Soc Nephrol 18:3177, 2007 10. Appel GB, Waldman M: The IgA nephropathy treatment dilemma. Kidney Int 69:1939, 2006 11. Ballardie FW, Roberts IS: Controlled prospective trial of prednisolone and cytotoxics in progressive IgA nephropathy. J Am Soc Nephrol 13:142, 2002 12. Donadio JV, Grande JP: The role of fish oil/omega-3 fatty acid in the treatment of IgA nephropathy. Semin Nephrol 24:225, 2004 13. Kim PK, Kim KS, Pai KS, et al: Long-term results of cyclosporine-induced remission of relapsing nephrotic syndrome in children. Yonsei Med J 38:307, 1997 14. Descoeudres B, Giannini O, Aschwanden M, et al: Silent recovery of native kidney function after transplantation in a patient with membranous nephropathy. Nephrol Dial Transplant 24:1345, 2009 15. Lai KN, Lai FM, Li PK, et al: Cyclosporin treatment of IgA nephropathy: a short term controlled trial. J Br Med J (Clin Res Ed) 295:1165, 1987 16. Tan CH, Lo PT, Yang WS, et al: Mycophenolate mofetil in the treatment of IgA nephropathy: a systematic review. Singapore Med J 49:780, 2008 17. Xu G, Tu W, Jiang D, et al: Mycophenolate mofetil treatment for IgA nephropathy: a meta-analysis. Am J Nephrol 29:362, 2009