Int Urol Nephrol DOI 10.1007/s11255-013-0627-4
NEPHROLOGY - LETTER TO THE EDITOR
Ocular complications after kidney transplantation: a case report and review of literature Zihret Abazi • Lidija Magarasevic • Svetlana Sukalo Natalija Kosanovic-Jakovic • Dusica Risovic
•
Received: 20 November 2013 / Accepted: 5 December 2013 Ó Springer Science+Business Media Dordrecht 2014
Abstract Membranoproliferative glomerulonephritis type II (MPGN II), also known as a dense deposit disease, is a chronic progressive kidney disease that often progresses to end-stage renal disease within 10 years. Most patients also have multiple subretinal white spots or drusen-like deposits that are histopathologically identical to the glomerular basement membrane deposits. The purpose is to determine ocular findings in a patient with MPGN II before and after renal transplantation and to correlate them with clinical characteristics related to transplantation and review of literature. We present a case of a 45-year-old female with MPGN II who developed bilateral serous retinal detachment and retinal hemorrhages in the left eye, which appeared 6 months after a renal transplant. Ocular
Z. Abazi (&) L. Magarasevic S. Sukalo D. Risovic Eye Clinic, Zvezdara University Medical Center, 161 Dimitrija Tucovica Street, 11000 Belgrade, Serbia e-mail: [email protected] L. Magarasevic e-mail: [email protected] S. Sukalo e-mail: [email protected] D. Risovic e-mail: [email protected] Z. Abazi Department of Ophthalmology, Health Center ‘‘Palilula’’, Belgrade, Serbia N. Kosanovic-Jakovic Eye Clinic, Clinical Center Serbia, Belgrade, Serbia e-mail: [email protected] N. Kosanovic-Jakovic D. Risovic School of Medicine, University of Belgrade, Belgrade, Serbia
complications in our case, with the exception on the retina, were present at the cornea and iris. Changes to the eyes were independent of the renal disease, because there was no recurrence of MPGN II on the renal graft. Keywords MPGN II Dense deposit disease Serous retinal detachment Visual loss
Introduction Membranoproliferative glomerulonephritis type II (MPGN II), also known as a dense deposit disease, is a chronic progressive renal disease characterized by the deposition of abnormal electron-dense material within the glomerular basement membrane of the kidney and often within Bruch’s membrane in the eye [1]. This disease is systemic, as evidenced by dense deposits in the kidney, splenic sinusoids, Bruch’s membrane (BM) of the retina, and its association with acquired partial lipodystrophy [2]. MPGN II is an aggressive disease that has a very high risk of recurrence (approaching 100 %). Individuals with MPGN II develop retinal drusen, often in the second decade of their life. The distribution of dense deposits in the initial stages of MPGN II is usually found on the fundus periphery and, initially, has a small impact on the decrease in visual acuity. The long-term risk for visual problems caused by drusen in MPGN II is approximately 10 % [1]. Many patients do not develop visual impairment, but some may lose vision as a result of the development of choroidal neovascularization (CNV) or central serous chorioretinopathy (CSCR). We reported an unusual case of severe ocular complications 6 months after the transplantation in a patient with MPGN II.
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Int Urol Nephrol
Case report The medical history of a 45-year-old female revealed a long-standing history of MPGN II, which was confirmed by a kidney biopsy in 2001. Due to the end-stage renal disease after hemodialysis, she received cadaveric kidney transplantation in 2012. A rare peripheral drusen-like deposit is occurred in the third decade of life. The regular annual ophthalmic examinations showed no progression of ocular manifestations. The preoperative ophthalmic findings revealed rare drusen-like deposits in the posterior pole, while findings of the anterior segment were normal. The best-corrected visual acuity (BCVA) was 6/6 in both eyes. After renal transplantation, time-zero graft biopsy was not performed due to a limited subcapsular hematoma in the inferior pole. She received polyclonal antibody (rATG) induction, followed by methylprednisolone, tacrolimus, and mycophenolate mofetil. Valganciclovir hydrochloride and trimethoprim-sulfamethoxazole were administered for cytomegalovirus and bacterial prophylaxis, respectively. Doppler ultrasonography was performed in which adequate renal perfusion and normal graft characteristics were observed. Three months after her kidney transplantation, ophthalmic findings were unchanged. Six months after the transplantation, the patient was admitted to our Ophthalmology department, because of a sudden decrease in visual acuity in both eyes. On admission, ophthalmic examination showed that her BCVA was reduced to hand movements in the left eye while it was 6/60 in the right eye. The slit-lamp examination of the anterior segment revealed a peripheral sterile corneal infiltrate and focal iris atrophy in the left eye (Figure 1a, b). Intraocular pressure of 14 mmHg and mild corticosteroidinduced cataracts were present in both eyes. Dilated fundus ophthalmoscopy in the left eye revealed intraretinal and preretinal hemorrhages, serous retinal detachment, and a large number of drusen-like deposits diffusely scattered in the posterior pole (Fig. 2a). Optical coherence tomography (SOCT Copernicus HRÒ; OPTOPOL Technology S.A., Poland) examination revealed subretinal fluid in the macula Fig. 1 Slit-lamp photograph shows corneal infiltration (a) and focal iris atrophy (b)
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(CSCR) and irregularities of BM with accumulation of hyper-reflective materials in the retinal pigment epithelium (RPE), which causes pigment epithelial detachment (PED) (Fig. 3). Dilated fundus examination in the right eye demonstrated a large number of drusen-like lesions and serous retinal detachment; there was neither hemorrhage nor CSCR (Fig. 2b). The patient underwent fundus autofluorescence, which revealed abnormal accumulation of lipofuscin around drusen-like lesions, while fluorescein angiography showed no evidence of CNV in both eyes. A complete laboratory workup was performed, and results were normal. At the Department of Nephrology, complete investigation revealed normal function and morphology of the graft. Treatment was started on prednisone 80 mg with topical diclofenac and oral acetazolamide 250 mg a day. After treatment, there was a withdrawal of retinal detachment and partial resorption of retinal hemorrhages, but visual acuity in both eyes remained unchanged, so she lost vision in her left eye.
Discussion Ocular manifestations in MPGN II were first described by Duvall-Young et al. in 1989, and J. Gass et al. [3, 4] first described three patients, in 1992, with segmental areas of RPE derangement in the posterior fundus associated with a secondary exudative detachment after kidney transplantation. Previous studies and long-term follow-up of patients with MPGN II have not shown a correlation between severity of kidney and eye disease, and it has been demonstrated that the risk of deterioration of visual acuity is small. Also, kidney transplantation does not increase the risk of progression of retinopathy [5, 6]. D’souza et al. [6] studied four patients who had MPGN type II, and these eye changes were monitored from 14 to 37 years. Three of them received a kidney transplant. There was no progression of retinopathy during the 10 years in any patients. None developed CNV or CSCR. In their study, A. Leys and colleagues showed that the type of fundus lesions was
Int Urol Nephrol
Fig. 2 Fundus photograph in OS showing preretinal and intraretinal hemorrhages below and nasally from optic nerve, serous retinal detachment, and drusen-like deposits diffusely scattered in the fundus
(a). Fundus photograph in OD showing drusen-like lesions that were diffusely scattered in the fundus and nasally present a large serous retinal detachment (b)
Fig. 3 OCT image in OS shows subretinal fluid typical for CSCR (white arrows). Yellow arrows indicate the drusen-like deposits in the Bruch’s membrane–retinal pigment epithelial interface, a region that
is morphologically similar to the capillary tuft–GBM–glomerular epithelial interface (a). The white arrow indicates PED, and the red arrow indicates serous retinal detachment (b)
statistically correlated with the duration of the renal disease, but not with age, sex, or renal insufficiency [7]. Retinal hemorrhages associated with MPGN II are rare and may be associated with CNV, or, as in our case, they may be due to the damage of the internal blood–retinal barrier (preretinal hemorrhages). Changes, which can be linked to post-transplant immunosuppressive therapy, include those of the anterior segment, such as corneal infiltration, iris atrophy, and cataracts. Also, sudden visual loss in the left eye was caused by hemorrhage in the macula and the CSCR. In our case, bilateral serous retinal detachment and retinal hemorrhage occurred after the transplantation, so renal transplantation could be a provoking factor for the development of severe retinopathy. Careful examination showed no systematic changes associated with the retinopathy, and we also excluded any other cause of the retinopathy. To our knowledge, this is a rare description of
significant progression of retinopathy following transplantation without recurrence on the graft. In the MPGN II patients, severe complications of the eyes may appear after kidney transplantation so frequent ophthalmic examinations are important. Acknowledgments The authors thank Aleksandra Radosavljevic, Assistant Professor of Ophthalmology, School of Medicine, University of Belgrade, for providing technical assistance and valuable comments. Conflict of interest The authors have no financial or proprietary interests related to this manuscript.
References 1. Appel GB, Cook HT, Hageman G et al (2005) Membranoproliferative glomerulonephritis type II (dense deposit disease): an
123
Int Urol Nephrol update. J Am Soc Nephrol 16:1392–1403. doi:10.1681/ASN. 2005010078 2. Mathieson PW, Peters DK (1997) Lipodystrophy and MCGN type II: the clue to links between the adipocyte and the complement system. Nephrol Dial Transplant 12:1804–1806. doi:10.1093/ndt/ 12.9.1804 3. Duvall-Yound J, MacDonald MK, McKechnie NM (1989) Fundus changes in (type II) mesangiocapillary glomerulonephritis simulating drusen: a histopathological report. Br J Ophthalmol 73:297–302 4. Gass JDM, Slamovits TL, Fuller DG, Gieser RG, Lean JS (1992) Posterior chorioretinopathy and retinal detachment after organ
123
transplantation. Arch Ophthalmol 110:1717–1722. doi:10.1001/ archopht.1992.01080240057030 5. Ponticelli C, Glassock RJ (2010) Posttransplant recurrence of primary glomerulonephritis. Clin J Am Soc Nephrol 5:2363–2372. doi:10.2215/CJN.06720810 6. D’souza Y, Short CD, McLeod D, Bonshek RE (2008) Long-term follow-up of drusen-like lesions in patients with type II mesangiocapillary glomerulonephritis. Br J Ophthalmol 92:950–953. doi:10.1136/bjo.2007.130138 7. Leys A, Van Damme B, Verberckmoes R (1996) Ocular complications of type 2 membranoproliferative glomerulonephritis. Nephrol Dial Transplant 11:211–214
NEPHROLOGY - LETTER TO THE EDITOR
Ocular complications after kidney transplantation: a case report and review of literature Zihret Abazi • Lidija Magarasevic • Svetlana Sukalo Natalija Kosanovic-Jakovic • Dusica Risovic
•
Received: 20 November 2013 / Accepted: 5 December 2013 Ó Springer Science+Business Media Dordrecht 2014
Abstract Membranoproliferative glomerulonephritis type II (MPGN II), also known as a dense deposit disease, is a chronic progressive kidney disease that often progresses to end-stage renal disease within 10 years. Most patients also have multiple subretinal white spots or drusen-like deposits that are histopathologically identical to the glomerular basement membrane deposits. The purpose is to determine ocular findings in a patient with MPGN II before and after renal transplantation and to correlate them with clinical characteristics related to transplantation and review of literature. We present a case of a 45-year-old female with MPGN II who developed bilateral serous retinal detachment and retinal hemorrhages in the left eye, which appeared 6 months after a renal transplant. Ocular
Z. Abazi (&) L. Magarasevic S. Sukalo D. Risovic Eye Clinic, Zvezdara University Medical Center, 161 Dimitrija Tucovica Street, 11000 Belgrade, Serbia e-mail: [email protected] L. Magarasevic e-mail: [email protected] S. Sukalo e-mail: [email protected] D. Risovic e-mail: [email protected] Z. Abazi Department of Ophthalmology, Health Center ‘‘Palilula’’, Belgrade, Serbia N. Kosanovic-Jakovic Eye Clinic, Clinical Center Serbia, Belgrade, Serbia e-mail: [email protected] N. Kosanovic-Jakovic D. Risovic School of Medicine, University of Belgrade, Belgrade, Serbia
complications in our case, with the exception on the retina, were present at the cornea and iris. Changes to the eyes were independent of the renal disease, because there was no recurrence of MPGN II on the renal graft. Keywords MPGN II Dense deposit disease Serous retinal detachment Visual loss
Introduction Membranoproliferative glomerulonephritis type II (MPGN II), also known as a dense deposit disease, is a chronic progressive renal disease characterized by the deposition of abnormal electron-dense material within the glomerular basement membrane of the kidney and often within Bruch’s membrane in the eye [1]. This disease is systemic, as evidenced by dense deposits in the kidney, splenic sinusoids, Bruch’s membrane (BM) of the retina, and its association with acquired partial lipodystrophy [2]. MPGN II is an aggressive disease that has a very high risk of recurrence (approaching 100 %). Individuals with MPGN II develop retinal drusen, often in the second decade of their life. The distribution of dense deposits in the initial stages of MPGN II is usually found on the fundus periphery and, initially, has a small impact on the decrease in visual acuity. The long-term risk for visual problems caused by drusen in MPGN II is approximately 10 % [1]. Many patients do not develop visual impairment, but some may lose vision as a result of the development of choroidal neovascularization (CNV) or central serous chorioretinopathy (CSCR). We reported an unusual case of severe ocular complications 6 months after the transplantation in a patient with MPGN II.
123
Int Urol Nephrol
Case report The medical history of a 45-year-old female revealed a long-standing history of MPGN II, which was confirmed by a kidney biopsy in 2001. Due to the end-stage renal disease after hemodialysis, she received cadaveric kidney transplantation in 2012. A rare peripheral drusen-like deposit is occurred in the third decade of life. The regular annual ophthalmic examinations showed no progression of ocular manifestations. The preoperative ophthalmic findings revealed rare drusen-like deposits in the posterior pole, while findings of the anterior segment were normal. The best-corrected visual acuity (BCVA) was 6/6 in both eyes. After renal transplantation, time-zero graft biopsy was not performed due to a limited subcapsular hematoma in the inferior pole. She received polyclonal antibody (rATG) induction, followed by methylprednisolone, tacrolimus, and mycophenolate mofetil. Valganciclovir hydrochloride and trimethoprim-sulfamethoxazole were administered for cytomegalovirus and bacterial prophylaxis, respectively. Doppler ultrasonography was performed in which adequate renal perfusion and normal graft characteristics were observed. Three months after her kidney transplantation, ophthalmic findings were unchanged. Six months after the transplantation, the patient was admitted to our Ophthalmology department, because of a sudden decrease in visual acuity in both eyes. On admission, ophthalmic examination showed that her BCVA was reduced to hand movements in the left eye while it was 6/60 in the right eye. The slit-lamp examination of the anterior segment revealed a peripheral sterile corneal infiltrate and focal iris atrophy in the left eye (Figure 1a, b). Intraocular pressure of 14 mmHg and mild corticosteroidinduced cataracts were present in both eyes. Dilated fundus ophthalmoscopy in the left eye revealed intraretinal and preretinal hemorrhages, serous retinal detachment, and a large number of drusen-like deposits diffusely scattered in the posterior pole (Fig. 2a). Optical coherence tomography (SOCT Copernicus HRÒ; OPTOPOL Technology S.A., Poland) examination revealed subretinal fluid in the macula Fig. 1 Slit-lamp photograph shows corneal infiltration (a) and focal iris atrophy (b)
123
(CSCR) and irregularities of BM with accumulation of hyper-reflective materials in the retinal pigment epithelium (RPE), which causes pigment epithelial detachment (PED) (Fig. 3). Dilated fundus examination in the right eye demonstrated a large number of drusen-like lesions and serous retinal detachment; there was neither hemorrhage nor CSCR (Fig. 2b). The patient underwent fundus autofluorescence, which revealed abnormal accumulation of lipofuscin around drusen-like lesions, while fluorescein angiography showed no evidence of CNV in both eyes. A complete laboratory workup was performed, and results were normal. At the Department of Nephrology, complete investigation revealed normal function and morphology of the graft. Treatment was started on prednisone 80 mg with topical diclofenac and oral acetazolamide 250 mg a day. After treatment, there was a withdrawal of retinal detachment and partial resorption of retinal hemorrhages, but visual acuity in both eyes remained unchanged, so she lost vision in her left eye.
Discussion Ocular manifestations in MPGN II were first described by Duvall-Young et al. in 1989, and J. Gass et al. [3, 4] first described three patients, in 1992, with segmental areas of RPE derangement in the posterior fundus associated with a secondary exudative detachment after kidney transplantation. Previous studies and long-term follow-up of patients with MPGN II have not shown a correlation between severity of kidney and eye disease, and it has been demonstrated that the risk of deterioration of visual acuity is small. Also, kidney transplantation does not increase the risk of progression of retinopathy [5, 6]. D’souza et al. [6] studied four patients who had MPGN type II, and these eye changes were monitored from 14 to 37 years. Three of them received a kidney transplant. There was no progression of retinopathy during the 10 years in any patients. None developed CNV or CSCR. In their study, A. Leys and colleagues showed that the type of fundus lesions was
Int Urol Nephrol
Fig. 2 Fundus photograph in OS showing preretinal and intraretinal hemorrhages below and nasally from optic nerve, serous retinal detachment, and drusen-like deposits diffusely scattered in the fundus
(a). Fundus photograph in OD showing drusen-like lesions that were diffusely scattered in the fundus and nasally present a large serous retinal detachment (b)
Fig. 3 OCT image in OS shows subretinal fluid typical for CSCR (white arrows). Yellow arrows indicate the drusen-like deposits in the Bruch’s membrane–retinal pigment epithelial interface, a region that
is morphologically similar to the capillary tuft–GBM–glomerular epithelial interface (a). The white arrow indicates PED, and the red arrow indicates serous retinal detachment (b)
statistically correlated with the duration of the renal disease, but not with age, sex, or renal insufficiency [7]. Retinal hemorrhages associated with MPGN II are rare and may be associated with CNV, or, as in our case, they may be due to the damage of the internal blood–retinal barrier (preretinal hemorrhages). Changes, which can be linked to post-transplant immunosuppressive therapy, include those of the anterior segment, such as corneal infiltration, iris atrophy, and cataracts. Also, sudden visual loss in the left eye was caused by hemorrhage in the macula and the CSCR. In our case, bilateral serous retinal detachment and retinal hemorrhage occurred after the transplantation, so renal transplantation could be a provoking factor for the development of severe retinopathy. Careful examination showed no systematic changes associated with the retinopathy, and we also excluded any other cause of the retinopathy. To our knowledge, this is a rare description of
significant progression of retinopathy following transplantation without recurrence on the graft. In the MPGN II patients, severe complications of the eyes may appear after kidney transplantation so frequent ophthalmic examinations are important. Acknowledgments The authors thank Aleksandra Radosavljevic, Assistant Professor of Ophthalmology, School of Medicine, University of Belgrade, for providing technical assistance and valuable comments. Conflict of interest The authors have no financial or proprietary interests related to this manuscript.
References 1. Appel GB, Cook HT, Hageman G et al (2005) Membranoproliferative glomerulonephritis type II (dense deposit disease): an
123
Int Urol Nephrol update. J Am Soc Nephrol 16:1392–1403. doi:10.1681/ASN. 2005010078 2. Mathieson PW, Peters DK (1997) Lipodystrophy and MCGN type II: the clue to links between the adipocyte and the complement system. Nephrol Dial Transplant 12:1804–1806. doi:10.1093/ndt/ 12.9.1804 3. Duvall-Yound J, MacDonald MK, McKechnie NM (1989) Fundus changes in (type II) mesangiocapillary glomerulonephritis simulating drusen: a histopathological report. Br J Ophthalmol 73:297–302 4. Gass JDM, Slamovits TL, Fuller DG, Gieser RG, Lean JS (1992) Posterior chorioretinopathy and retinal detachment after organ
123
transplantation. Arch Ophthalmol 110:1717–1722. doi:10.1001/ archopht.1992.01080240057030 5. Ponticelli C, Glassock RJ (2010) Posttransplant recurrence of primary glomerulonephritis. Clin J Am Soc Nephrol 5:2363–2372. doi:10.2215/CJN.06720810 6. D’souza Y, Short CD, McLeod D, Bonshek RE (2008) Long-term follow-up of drusen-like lesions in patients with type II mesangiocapillary glomerulonephritis. Br J Ophthalmol 92:950–953. doi:10.1136/bjo.2007.130138 7. Leys A, Van Damme B, Verberckmoes R (1996) Ocular complications of type 2 membranoproliferative glomerulonephritis. Nephrol Dial Transplant 11:211–214
