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Purpose: The purpose of this study was to describe the surgical management of bilateral giant full-thickness macular hole with sudden onset two months after cataract surgery in a patient with Alport syndrome., Methods: This was an observational, single-case report., Results: A 54-year-old woman with a history of Alport syndrome presented with severe bilateral visual loss two months after cataract surgery. The diagnosis of bilateral giant full-thickness macular hole was made. We found the absence of the internal limiting membrane and the inability to lift and peel a continuous posterior hyaloid sheet during surgical management with 25-gauge pars plana vitrectomy (left eye). Amniotic membrane grafting followed by gas tamponade were performed for hole closure. The hole remained closed but vision was poorly restored two months after., Conclusion: Cataract surgery in patients with Alport syndrome could promote early development of giant full-thickness macular hole. Collagen defects could underlie internal limiting membrane absence and the inability to properly peel the posterior hyaloid., (Copyright © 2024 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the Opthalmic Communications Society, Inc.)

Alport syndrome is characterized by type IV collagen network disruptions leading to renal, auditory, and ocular manifestations. This case report details a 24-year-old man with Alport syndrome who developed a rhegmatogenous retinal detachment following macular hole repair. The patient underwent a successful vitrectomy and internal limiting membrane peel for macular hole repair but returned with vision loss due to retinal detachment five weeks later, which necessitated a combined scleral buckle and vitrectomy. This is the first case describing rhegmatogenous retinal detachment post-macular hole repair in Alport syndrome. [ Ophthalmic Surg Lasers Imaging Retina 2024;55:289-292.] .

The authors present a case of a thirty-eight-year-old patient with Alport syndrome. The patient had several ocular symptoms of the disease and has been treated for systemic problems in connection with Alport syndrome since he was fifteen years old. At that age the patient also underwent a kidney transplant in order to deal with renal insufficiency. To date, he still uses immunosuppressants and antihypertensives. Furthermore, the patient suffers from perceptive deafness. The patient visited our clinic in 2021 with a request to solve his high refractive error, in which the diopters were so high that it was not possible to place them in spectacles. The patient's best corrected visual acuity was 0.6 with -8.0sph/-4.0cyl/ax15 in the right eye and 0.7partim with -8.0sph/-4.0cyl/ax155 in the left eye. The autorefractometer values were -6.25sph/-6.75cyl/ax17 in the right eye and -6.75sph/-6.5cyl/ax155 in the left eye. During the eye examination we found a number of ocular manifestations that are typical of Alport syndrome. On the cornea there were opacities as a residue of corneal erosions, and at one of the following check-ups we also found a newly developed corneal erosion. Subsequently, we found an anterior lenticonus and incipient cataract. Upon performing OCT, a typical temporal macular atrophy was evident. Fundus examination in artificial mydriasis showed just a minimal manifestation of fleck retinopathy. Due to the clinical manifestation we decided to perform cataract surgery and implant a monofocal toric intraocular lens in both eyes. There were no complications during the operations, however the surgeon registered a non-standard structure of the lens capsule. The capsule was more fragile, and performing capsulorhexis was much more complicated. A week after the surgery, higher cylinder diopters were still present. A decrease of the higher diopters was noticeable one month after surgery. The time interval between the first operation and the second operation was one month. The patient was highly satisfied with result, and uncorrected visual acuity improved by over four lines. After surgery the patient needed low diopters for near as well as far distance. In the case of this patient, the ocular manifestations were detected and treated in adulthood. Nevertheless, early detection of ocular symptoms of Alport syndrome in young patients before renal failure could lead to timely start of the treatment and delay a possible renal transplant. In case of any suspicion of Alport syndrome it is advised to send the patient to a pediatrician, and at an older age to an internal medicine specialist, for further examination.

Purpose: To report the structural and functional outcomes of autologous neurosensory retinal transplantation for closure of refractory double full-thickness macular hole in a patient diagnosed with Alport syndrome., Methods: Patient with previous pars plana vitrectomy and a failed macular hole surgery (internal limiting membrane removal) underwent pars plana vitrectomy and autologous neurosensory retinal flap transplantation with silicone oil tamponade. Follow-up was performed after one year. The anatomic outcomes were evaluated mainly by fundus examination, optical coherence tomography (OCT), and microperimetry (MAIA). The functional changes were evaluated comparing best-corrected visual acuities preoperative and 1 year after surgery., Results: A 35-year-old man with progressive visual loss of two years of evolution presented a double full-thickness macular hole in the left eye. After retinal flap transplantation, the macular hole appeared successfully closed during the entire follow-up. Integration of both retinal flaps into the surrounding retina and regeneration of the external retinal layers were observed in optical coherence tomography. Best-corrected visual acuities improved from 20/200 preoperatively to 20/80 one-year postoperatively., Conclusion: Pars plana vitrectomy combined with autologous neurosensory retinal flap transplantation is an effective option to achieve the anatomic closure of recurrent double full-thickness macular hole and significant visual recovery in Alport syndrome.

Background: Registry data from Europe has shown an increase in age at end-stage kidney disease for patients with Alport syndrome in recent years. Whether a similar delay in transplant age has occurred in the United States for Alport patients across all racial/ethnic groups is unknown., Materials and Methods: We used data from the Scientific Registry of Transplant Recipients (SRTR) to identify 3,794 Alport patients transplanted between 12/1987 and 12/2017. We divided the study period into five equal eras to assess temporal trends in age at transplant, graft survival, and patient survival across racial groups using linear regression and Cox regression models., Results: The mean age at transplant for Blacks (28.3 years; difference (Black vs. White): 8.9 years; p < 0.0001) and Hispanics (28.7 years; difference (Hispanics vs. White): 8.7 years; p < 0.0001) was significantly younger compared with that of Whites. We observed a temporal increase in age at transplant for Whites but not for Blacks and Hispanics (p-value for interaction: 0.001). Black recipients were at a higher risk of graft loss (aHR: 1.78; 95% CI: 1.47, 2.15; p < 0.0001) and death (aHR: 1.73; 95% CI: 1.11, 2.69; p = 0.02) compared with White recipients. We observed significant improvements in graft survival with each successive era (p < 0.01). Temporal trends in graft survival (interaction p = 0.46) were not modified by race., Conclusion: We found racial disparities in age at transplant and long-term graft survival for patients with Alport syndrome in the United States. The age at transplant increased over time for Whites but not Black and Hispanic patients.

Recurrent toxic shock syndrome (TSS) is uncommon. A certain level of clinical suspicion is indicated with a complex sepsis presentation in the postoperative kidney transplant patient. We present a case of presumed recurrent postoperative TSS in a living kidney transplant recipient. The patient was a 19-year-old Caucasian female with a 4-year prior single episode of toxin-mediated sepsis and chronic kidney disease (CKD) secondary to autosomal recessive Alport's syndrome (confirmed via renal biopsy and genetic testing). She received a human leukocyte antigen (HLA) 2A 2B 1DR MM, CMV -D/-R kidney from her 21-year-old friend. The patient received Campath and IV steroid induction after total cold ischemic time of 170 minutes with 40 minutes of revascularization. On postoperative day (POD) 5, she required re-exploration with reimplantation and stenting of the transplanted ureter. The patient subsequently spiked a fever of 101.6° with a generalized rash prompting collection of blood cultures which demonstrated no growth. Infectious Disease was consulted due to persistent fevers despite IV antibiotics. On POD 12, the patient returned to the operating room (OR) for evacuation of hematoma after decline in Hgb to 5.8 and CT confirmed perinephric hematomas. Kidney biopsy showed no rejection and donor specific antibodies (DSAs) were unremarkable. The patient underwent 1 treatment of empiric plasmapheresis for possible non-HLA antibodies followed by initiation of clindamycin. The patient's condition improved, and she was discharged home with a normal creatinine. Recurrent TSS is rare but should be added to the differential diagnoses of immuno-compromised patients undergoing kidney transplantation with a history of prior toxin-mediated sepsis.

Alport syndrome (AS) is an inherited disorder of basement membranes caused by mutations affecting specific proteins of the type IV collagen family, presenting with nephropathy and extrarenal manifestations such as sensorineural deafness and ocular anomalies. Ten percentage to 15% of the patients with AS have autosomal recessive (ARAS) due to mutation in either COL4A3 or COL4A4 gene. We report a novel mutation in the COL4A3 gene in an Indian family with ARAS. The above-mentioned genetic anomaly was a missense variation in exon 26 of the COL4A3 gene (chr2:228137797G>A; c.1891G>A) that resulted in the amino acid substitution of Arginine for Glycine at codon 631 (p.Gly631Arg) that was present in the heterozygous state in the asymptomatic parents and homozygous state in the male offspring who presented with early-onset end-stage renal disease, lenticonus and hearing loss. The patient (male offspring) underwent successful renal transplantation with his mother as a donor., (© 2020 Asian Pacific Society of Nephrology.)

Alport-leiomyomatosis syndrome is an extremely rare condition occurring at a young age in which Alport syndrome coexists with diffuse leiomyomatosis of the digestive tract (primarily the esophagus). Most patients with diffuse esophageal leiomyomatosis require esophagectomy of variable extents. A 20-year-old man with Alport-leiomyomatosis syndrome was diagnosed with dysphasia and hematuria in childhood. Although he underwent partial esophagogastrectomy at 8 years of age, extremely severe gastroesophageal reflux symptoms were noted postoperatively. He was diagnosed with refractory severe reflux esophagitis associated with diffuse leiomyomatosis and esophagogastric anastomosis, for which he underwent subtotal esophagectomy, gastric tube reconstruction, and esophagogastric anastomosis in the left neck. The postoperative course was generally good, and he had no postoperative reflux symptoms. To achieve long-term control of symptoms, the lesion must be removed completely; nevertheless, unnecessarily extensive esophagectomy should be avoided.

Background: Kidney transplantation is the treatment of choice in end-stage renal disease due to Alport syndrome (AS). However, the chances of finding an adequate living-related donor in AS are much worse compared to non-heritable conditions. Successful cases of related living-donor transplantation mostly refer to X-linked AS but are rarely reported in genetically confirmed autosomal AS., Case Presentation: We describe the outcome of an exceptional AB0-incompatible kidney donation from father to son in a family with altered COL4A3. While decision-making was based on extensive clinical donor evaluation prior to transplantation, we analyzed the underlying genetic background in retrospect and associated these findings with the phenotype in all available family members. While biallelic COL4A3 variants caused autosomal recessive AS (ARAS) in the son (recipient), heterozygous family members, including the father (donor), showed minimal renal involvement and high-frequency sensorineural hearing impairment later in life indicating mild autosomal dominant Alport syndrome (ADAS). The recipient's successful participation in the European and World Transplant Games is a testament to the positive outcome of transplantation., Conclusions: In summary, living-related donor transplantation may be successful in autosomal AS, provided that thorough clinical and genetic evaluation of potential donors is performed. However, unrelated kidney transplantation should be given priority upon unpredictable genetic risk. Individual genetic variant interpretation is an important component of personalized donor assessment and will help to better predict genetic risk in the future.

Rationale: To report the visual status and results of phacoemulsification cataract surgery in a young patient with Alport syndrome associated with bilateral anterior lenticonus. The milestone of this report is the use of anterior segment optical coherence tomography (AS-OCT) to confirm the central protrusion of the anterior surface of the crystalline lens., Patient Concerns: A 23-year-old young woman presented with severe progressive visual loss in both eyes, which started several years ago., Diagnoses: Refractive status was indicative of high myopia with astigmatism and vision was not improved with optimal correction to better than 0.1 in the right eye and 0.2 in the left eye (visual acuities given in decimal notation). Slit-lamp examination showed transparent cornea, anterior lenticonus and posterior sub-capsular cataract in both eyes. The classical appearance of oil droplet was evident using retro-illumination on the slit lamp., Interventions: The natural lenses were replaced with intraocular lens (IOL)., Outcomes: An excellent refractive status achieved associated with an uncorrected distance visual acuity 0.9 and 0.8 in the right and left eye, respectively., Lessons: AS-OCT is a valuable device for confirming the budging of the anterior crystalline lens surface.

Background: Retinal microvascular disease reflects, in part, poor blood pressure control and systemic microvascular disease contributes to renal failure progression. This study examined the retinal microvasculature in Alport syndrome., Materials and Methods: Retinal images from 28 males and 28 females with X-linked Alport syndrome, and 13 individuals with autosomal recessive disease were reviewed retrospectively for microvascular/ hypertensive retinopathy (Wong and Mitchell classification), and small vessel calibre (using a computerised semiautomated method and revised Knudtson formula). Data were compared with age and gender-matched individuals with normal blood pressure and renal function., Results: Microvascular/hypertensive retinopathy was more common in males and females with X-linked Alport syndrome than age- and gender-matched controls (23, 82% and 10, 36%, p < 0.01; and 21, 75% and 13, 48%, p = 0.05, respectively), and in individuals with autosomal recessive disease compared with controls (12, 92% and 16, 43%, p < 0.01). Moderate microvascular/hypertensive changes were present in males and females with X-linked or autosomal recessive disease but not controls. Arteriolar calibre was reduced in males with X-linked disease (142.5 ± 18.7 µm, and 150.7 ± 10.1 µm, p = 0.046) and in autosomal recessive disease (133.5 ± 11.10 µm and 149.1 ± 10.6 µm, p < 0.0001). Microvascular/hypertensive retinopathy and arteriolar narrowing in males with X-linked disease were not different after renal transplantation and before (p NS)., Conclusions: Microvascular/hypertensive retinopathy was more common and more severe in Alport syndrome than normotensive controls. Improved BP levels may further slow the rate of renal functional decline in Alport syndrome.

Alport syndrome (AS) and thin basement membrane lesions are caused by various mutations in type IV collagen genes. Although AS is considered a rare disease, thin basement membrane is a frequent pattern, especially in families with a history of persistent hematuria. We report a patient with a diagnosis of AS who developed end-stage kidney disease (ESKD) and received a kidney transplant from a living unrelated donor. The graft biopsy specimen surprisingly showed a pattern of thin basement membranes., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Objective: We aim to describe management of a patient receiving renal transplantation for chronic renal failure due to Alport syndrome with low dose of intrathecal bupivacaine and continuous epidural infusion of local anesthetic., Case Report: A 38-years-old man with chronic renal failure secondary to Alport syndrome underwent kidney transplantation. Because of a high risk of respiratory and cardiovascular complications related to the patient's baseline lung disease and abnormalities in heart conduction, we selected combined spinal-epidural anesthesia. The block was ultrasound-guided and performed at the T12-L1 interspace with 4.5 mg of 0.5% intrathecal hyperbaric bupivacaine followed by a continuous epidural infusion of 0.5% levobupivacaine mixed with 25 μg of Fentanyl at the initial rate of 8 mL/h. Sensory block to T5-T6 was obtained within 10 minutes. The patient then received mild sedation with Propofol and Remifentanil. Methylprednisolone and diuretics were administered before vascular unclamping according to our internal protocol. Surgery lasted 3 hours with no clinical or procedural complication., Conclusions: Although renal transplantation is usually performed under general anesthesia, in a particularly complex patient with chronic renal failure, chronic obstructive pulmonary disease and a worsened respiratory mechanics, we applied a combined approach with a low dose of intrathecal bupivacaine and continuous epidural infusion of local anesthetic. The technique did not affect hemodynamics while having a positive impact on recovery of function of the transplanted organ with rapid improvement of urine output, serum creatinine, and blood urea nitrogen levels., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Aim: To evaluate the results of kidney transplantation from alive related donor in patients with Alport syndrome and to compare with those in patients with kidney hypoplasia., Material and Methods: We have analyzed 8 and 27 medical records of patients with Alport syndrome and kidney hypoplasia respectively. Following parameters were used - Kaplan-Meier survival analysis, Wilcox overall risk, percentage of transplants loss and mortality (Fisher's exact test calculation)., Results: It is concluded that percentage of transplants loss and mortality rate as well as overall survival and risk were similar in both groups., Conclusion: Despite risk of anti-GBM nephritis development in patients with Alport syndrome results are comparable with those after transplatation for chronic renal failure caused by other reasons.

Renal denervation is a new intervention to treat resistant hypertension. By applying radiofrequency (RF) to renal arteries, sympathetic nerves in adventitia layer of vascular wall can be denervated. Sympathetic hyperactivity is an important contributory factor in hypertension of hemodialysis patients. Hyperactive sympathetic nervous system aggravates hypertension and it can cause complications like left ventricular hypertrophy, heart failure, arrhythmias and atherogenesis. Our report illustrates the use of renal denervation using conventional RF catheter for uncontrolled hypertension in a patient with Alport syndrome and rejected renal allograft. Progressive and sustained reduction of blood pressure was obtained post-procedure and at 24 months follow-up with antihypertensives decreased from 6 to 2 per day, thereby demonstrating the safety, feasibility, and efficacy of the procedure. There are some reports available on the usefulness of this technique in hemodialysis patients; however, there are no studies of renal denervation in patients with Alport syndrome and failed allograft situation., (Copyright © 2015 Cardiological Society of India. Published by Elsevier B.V. All rights reserved.)

Hepatitis E virus genotype-3 (HEV3) infection can cause chronic hepatitis in immunosuppressed patients and induce extra-hepatic manifestations, such as neurological symptoms, kidney injuries, and immune-mediated thrombocytopenia. Very few cases of HEV-induced kidney manifestations have been reported. Herein, we report, for the first time, a case of de novo membranoproliferative glomerulonephritis that occurred in a kidney transplant patient who developed a chronic HEV3 infection, which was successfully treated with ribavirin., (© 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

We report a fatal case of alemtuzumab-induced diffuse alveolar hemorrhage in an 18-year-old male with Alport syndrome. The patient developed acute onset shortness of breath, hemoptysis and fever after renal transplantation. Computed tomography findings were consistent with adult respiratory distress syndrome. Bronchoscopy and broncho-alveolar lavage was performed that showed no evidence of pathogenic bacteria or opportunistic infection. The patient was intubated and ventilated because of worsening respiratory function. The patient received plasma electrophoresis and was maintained on tacrolimus and steroids; however, unfortunately the patient died 31 days post-transplantation due to worsening respiratory function and declining graft function. Although the prevalence and the exact mechanism of this fatal complication remain unknown, an awareness of this complication is important to all clinicians using alemtuzumab. This is a second report of diffuse alveolar hemorrhage secondary to alemtuzumab induction in patients with Alport syndrome., (Copyright © 2015. Published by Elsevier Inc.)

Purpose: To report the ocular findings of patients with Alport syndrome and the results of clear lens extraction in this patient group., Methods: Twenty-three eyes of 15 patients with a diagnosis of Alport syndrome were included in this study. Clear corneal phacoemulsification and intraocular foldable lens implantation was performed in eyes with indeterminate refractive errors and/or poor visual acuity and anterior capsule samples were analyzed with electron microscopy., Results: All patients had a history of hereditary nephritis and/or deafness as systemic involvement. Ophthalmologic examination revealed anterior lenticonus with high myopia and/or irregular astigmatism in all patients. The mean best-corrected visual acuity (BCVA) was 0.67 ± 0.17 logMAR (range 1.0-0.4) preoperatively and 0.17 ± 0.08 logMAR (range 0.3-0.0) postoperatively. Postoperative refractive lenticular astigmatism dramatically decreased and no ocular complications arose during the follow-up period. Transmission electron microscopic analysis of the lens capsules supported the diagnosis of Alport syndrome., Conclusions: Clear lens phacoemulsification and foldable intraocular lens implantation is a safe and effective therapeutic choice for the management of uncorrectable refractive errors and low visual acuity due to anterior lenticonus in patients with Alport syndrome.

Alport syndrome with diffuse leiomyomatosis (ASDL) is a complex combination that doesn't have a specific course of treatment. In this case report, we present a 44-year-old woman with ASDL and detail her treatment. The patient presented at the emergency room (ER) with symptoms of anemia, bronchial asthma, and abnormal uterine bleeding (AUB). The patient had diffuse myomas in different areas of her body, including the esophagus and genital tract. She was treated by a multidisciplinary team that included members from the hematology/oncology, pulmonary, interventional radiology, anesthesia, surgery, and gynecology services. A physician from interventional radiology performed an embolization of the uterine arteries to treat the patient's AUB. Surgery was done in May 2011 to remove the esophageal leiomyomas to improve her pulmonary function. Surgery included a distal esophagectomy, a proximal gastrostomy, and the resection of the leiomyomatous mass. In order to shrink the tumor in her genito pelvic region so that it could be extirpated with the highest likelihood of success, the patient was treated with gonadotropin-releasing hormone agonist (leuprolide acetate, 3.75 mg/month for 4 months). In May 2012, the patient had a total abdominal hysterectomy (TAH), with a bilateral salpingo-ophorectomy (BSO), the excision of a leiomyoma, and a posterior colporrhaphy.

Unintentional weight loss in a renal transplant recipient is an important condition, requiring diagnostic search within the framework of malignancy and opportunistic infections. To the best of our knowledge, there are no data in the literature reporting underlying coeliac disease as the cause of significant weight loss after renal transplant. We report a 32-year-old woman, who complained of significant weight loss during the 3.5 years posttransplant. Diagnostic work-up revealed coeliac disease, and a gluten-free diet stabilized her weight loss. Considering the high frequency of coeliac disease, this should be kept in the differential diagnosis of renal transplant recipients presented with weight loss and other suggestive features.

Alport post-transplant nephritis (APTN) is an aggressive form of anti-glomerular basement membrane disease that targets the allograft in transplanted patients with X-linked Alport syndrome. Alloantibodies develop against the NC1 domain of α5(IV) collagen, which occurs in normal kidneys, including renal allografts, forming distinct α345(IV) and α1256(IV) networks. Here, we studied the roles of these networks as antigens inciting alloimmunity and as targets of nephritogenic alloantibodies in APTN. We found that patients with APTN, but not those without nephritis, produce two kinds of alloantibodies against allogeneic collagen IV. Some alloantibodies targeted alloepitopes within α5NC1 monomers, shared by α345NC1 and α1256NC1 hexamers. Other alloantibodies specifically targeted alloepitopes that depended on the quaternary structure of α345NC1 hexamers. In Col4a5-null mice, immunization with native forms of allogeneic collagen IV exclusively elicited antibodies to quaternary α345NC1 alloepitopes, whereas alloimmunogens lacking native quaternary structure elicited antibodies to shared α5NC1 alloepitopes. These results imply that quaternary epitopes within α345NC1 hexamers may initiate alloimmune responses after transplant in X-linked Alport patients. Thus, α345NC1 hexamers are the culprit alloantigen and primary target of all alloantibodies mediating APTN, whereas α1256NC1 hexamers become secondary targets of anti-α5NC1 alloantibodies. Reliable detection of alloantibodies by immunoassays using α345NC1 hexamers may improve outcomes by facilitating early, accurate diagnosis.

We report a 28-year-old mole with a hereditary nephritis (Alport Syndrome) on hemodialysis for 5 years, who received a kidney graft from a deceased donor. Cyclosporine (CsA), mycophenolate mofetil (MMF) and steroids were prescribed. In the postoperative period the patient had thrombophlebitis and diarrhea. A CT sean showed splenomegaly, ascites, bilateral pleural effusion and bowel edema. Laboratory showed hypoalbuminemia, increased C reactive protein (CRP) and panhypogammaglobulinemia. At day 32 after transplantation, an acute rejection (Banff II b) was diagnosed and treated with methylprednisolone, replacing CsA by tacrolimus. The acute rejection was controlled but six days later, high fever, pancytopenia and hyperferritinemia appeared. A bone marrow smear showed numerous histiocytes and hemophagocytosis. Hemophagocytic syndrome was diagnosed. MMF and tacrolimus were withdrawn and CsA was reinstituted. Fever fell quickly, CPR normalized at 24 hours and white blood cell count at 72 hours. Days later, the concentrations of albumin, immunoglobulins and hematological parameters normalized. The patient was discharged on day 57 after admission in good condition.

Background and Objectives: Patients with the hereditary disease Alport syndrome commonly require renal replacement therapy (RRT) in the second or third decade of life. This study compared age at onset of RRT, renal allograft, and patient survival in men with Alport syndrome receiving various forms of RRT (peritoneal dialysis, hemodialysis, or transplantation) with those of men with other renal diseases., Design, Setting, Participants, & Measurements: Patients with Alport syndrome receiving RRT identified from 14 registries in Europe were matched to patients with other renal diseases. A linear spline model was used to detect changes in the age at start of RRT over time. Kaplan-Meier method and Cox regression analysis were used to examine patient and graft survival., Results: Age at start of RRT among patients with Alport syndrome remained stable during the 1990s but increased by 6 years between 2000-2004 and 2005-2009. Survival of patients with Alport syndrome requiring dialysis or transplantation did not change between 1990 and 2009. However, patients with Alport syndrome had better renal graft and patient survival than matched controls. Numbers of living-donor transplantations were lower in patients with Alport syndrome than in matched controls., Conclusions: These data suggest that kidney failure in patients with Alport syndrome is now being delayed compared with previous decades. These patients appear to have superior patient survival while undergoing dialysis and superior patient and graft survival after deceased-donor kidney transplantation compared with patients receiving RRT because of other causes of kidney failure.

Brown tumor is a rare complication of secondary hyperparathyroidism. It is exceptionally encountered after kidney transplantation. We here report on a 54-year-old male recipient who developed a brown tumor localized in the right forearm, and whose initial presentation was atypical, mimicking a bone tumor. Hence, diagnosis of brown tumors should be suggested by clinicians in a context of hyperparathyroidism., (Copyright © 2012 Elsevier Inc. All rights reserved.)

Renal cell carcinoma (RCC) is considered a contraindication for transplant. However, an increasing number of cases of transplant kidneys with RCC have been reported with encouraging results. We present our experience of two cases of transplanting kidneys with small RCCs. Donors and recipients were aware of the presence and possible consequences of RCC in the transplanted kidney before transplantation. Cases were discussed in the multidisciplinary team meetings. Regular, 6-12 monthly follow-up of donors and recipients was carried out with ultrasonography and/or computed tomography to detect recurrence of RCC or new tumours in the recipients' transplant kidneys or the donors' native kidneys. The outcome was recorded. There were no suspicious masses in the any of the kidneys during the follow-up period. The transplant kidneys are functioning.

We present the case of a 36-year-old male patient who presented with an increasing bilateral loss of vision which had existed for several years. Slit-lamp examination revealed a conical anterior protusion of the lens and funduscopy showed a discreet perimacular dot and fleck retinopathy. In consideration of all clinical findings the patient was diagnosed with anterior lenticonus as an ocular manifestation of an Alport's syndrome which is a rare X-linked disease. Besides renal failure and hearing loss which occur early, ocular changes usually manifest later on. Patients with a anterior lenticonus can be effectively treated with phacoemulsification and intraocular lens implantation. The visual outcome after surgery is excellent.

Background: Hepatitis E virus (HEV) infection is an emerging disease in industrialized countries. Few data regarding genotype 3 HEV extrahepatic manifestations exist., Methods: We assessed kidney function and histology in solid-organ transplant patients during HEV infection. In all, 51 cases of genotype 3 HEV infections were diagnosed (34 kidney, 14 liver, and 3 kidney-pancreas transplant patients). Of these, 43.2% were cleared of the virus spontaneously within 6 months of infection, whereas 56.8% evolved to chronic hepatitis. Twelve of these patients completed a 3-month antiviral therapy and were followed up for 6 months posttreatment. Kidney function (estimated glomerular filtration rate [eGFR] obtained by the Modification of Diet in Renal Disease equation) and proteinuria were assessed before infection, during HEV infection and during follow-up. Kidney biopsies were obtained from patients with high proteinuria and decreased eGFR levels., Results: During HEV infection, there was a significant decrease in eGFR in both kidney- and liver-transplant patients. Glomerular diseases were observed in kidney biopsies obtained during the acute and chronic phases. This included membranoproliferative glomerulonephritis and relapses in IgA nephropathy. The majority of patients had cryoglobulinemia that became negative after HEV clearance. Kidney function improved and proteinuria decreased after HEV clearance., Conclusion: HEV-associated glomerulonephritis seems to be an HEV-related extrahepatic manifestation. Further studies are required to confirm these observations.

Background: Anti-glomerular basement membrane (anti-GBM) nephritis post-renal transplantation (RTx) is known to cause graft loss in Alport's syndrome (AS). We evaluated the results of RTx in AS patients vis à vis patient and graft survivals, incidence of anti-GBM nephritis, and causes of graft failure., Materials and Methods: Between 1993 and 2009 we performed 31 RTx on AS patients (28 males and three females) of overall mean age of 22 ± 7.9 years from six deceased and 27 living donors. Two patients underwent second RTx., Results: Over a follow-up of 1, 3, 5, and 10 years, the mean serum creatinines (mg/dL) were 1.51 ± 0.52, 1.59 ± 0.26, 1.61 ± 0.30, and 1.63 ± 0.32, respectively. Patient survivals at 1, 5, and 10 years were 89.71%, 81.32% and 81.32% with graft survival for all periods of 81.2%. Twenty-one percent experienced biopsy-proven acute rejection episodes. Graft failures were due to anti-GBM nephritis in 12.2% (n = 4), chronic allograft nephropathy in 3.2% (n = 1), and acute rejection or cyclosporine toxicity 3.2% (n = 1 each). The mean duration to graft loss was 4.9 ± 2.4 months., Conclusion: Graft and patient survivals were acceptable among transplant recipients with AS despite the risk of anti-GBM nephritis., (Copyright © 2012 Elsevier Inc. All rights reserved.)

A 56-year-old patient with renal insufficiency secondary to Alport syndrome presented for kidney transplantation from an unrelated living donor. The recipient had a medical history that included 2 episodes of malignant hyperthermia: in 1989 and 1991. On both occasions she was treated with dantrolene. The patient had not undergone muscle biopsy testing but was considered malignant hyperthermia susceptible (MHS) based on clinical history. Both the kidney donor and the recipient underwent nontriggering general anesthetics using total intravenous anesthesia techniques without the use of prophylactic dantrolene. Using this technique, the MHS kidney recipient did not experience a malignant hyperthermia episode perioperatively. The donor and the recipient had uneventful clinical courses, and to date the renal transplantation has been successful.

Purpose: Alport syndrome is a hereditary basement membrane disease that typically involves the kidney, the cochlea, and the eyes. Characteristic ocular problems include posterior polymorphous corneal dystrophy, lenticonus, and dot-and-fleck retinopathy., Methods: A 48-year-old male patient with Alport syndrome presented with corneal and retinal changes. In 2003, he was diagnosed with posterior polymorphous corneal dystrophy and received a corneal transplant in his left eye in 2007 because of progressive deterioration in visual acuity. At this time, a lamellar macular hole was diagnosed in his right eye. The removed corneal button was examined by light and electron microscopy and by immunohistochemistry., Results: Histology revealed not only endothelial changes but also a marked irregular thickening of the epithelial basement membrane and of Bowman layer. Alcian blue staining demonstrated an accumulation of mucopolysaccharides in the Bowman layer., Conclusions: The presented changes underline the great variation of ocular disorders related to Alport syndrome. To our knowledge, this is one of the first reports describing histologic corneal findings in Alport syndrome. Only a few cases with accumulation of mucopolysaccharides in the Bowman layer have been described previously, none of them being associated with Alport syndrome. Besides, anterior corneal alterations and corneal clouding seem to be uncommon in patients suffering from Alport syndrome.

It is fascinating to note the astute observations of clinicians almost a century ago. Familial hematuria was described in 1902 by Dr. Leonard Guthrie. Dr. Cecil Alport refined the disease description in 1927. (Both papers are still available online.) Applications for life insurance were recently received on two women who had Alport syndrome as a known diagnosis. The cases will be presented and used as a springboard to discuss Alport syndrome and benign familial hematuria (BFH).

Patients with some hereditary nephropathies-including autosomal dominant polycystic kidney disease (ADPKD), Fabry disease and Alport syndrome-can progress to end-stage renal disease (ESRD) and are candidates for kidney transplantation. When considering whether a potential living donor is appropriate for a particular patient, clinicians should be aware of the increased risk of adverse outcomes for the donor and the recipient. Renal transplantation from a living related donor is not contraindicated in most nephropathies that have an autosomal recessive mode of inheritance (for example, autosomal recessive polycystic kidney disease and cystinosis). Renal transplant recipients with ADPKD, however, should only receive a kidney from a related donor if the disease has been excluded in the donor by imaging and/or genetic testing. Potential living related donors for patients with Alport syndrome should be evaluated carefully for the presence of microhematuria and microalbuminuria before a decision is made to perform transplantation, and mothers or heterozygous sisters of affected male recipients with X-linked Alport syndrome should be informed about the possible long-term increased risk of renal dysfunction associated with donation. Most patients with atypical hemolytic uremic syndrome should not receive a kidney transplant from a living donor because there is a high risk of disease recurrence and graft loss.

Hepatitis E virus (HEV) can induce chronic hepatitis in immunosuppressed patients. There is no established treatment for HEV infection. Pegylated interferon-alpha-2a (Peg-IFN-alpha-2a) has been successfully used for treating HEV infection in liver transplant patients with chronic hepatitis. A kidney transplant patient with chronic HEV infection evolved to end-stage kidney disease and started haemodialysis. Three months after immunosuppressive therapy was stopped, HEV RNA was still detected both in serum and in stools. Before considering a retransplantation, we decided to initiate Peg-IFN-alpha-2a therapy to eradicate the virus. A 3-month course of Peg-IFN-alpha-2a was scheduled, and the latter was started at the weekly dose of 135 microg. Serum HEV RNA became negative by Week 3 of Peg-IFN-alpha-2a therapy, and remained negative until the last follow-up, i.e. 6 months after anti-viral therapy was stopped. Hence, we report the first known case of a 3-month course of Peg-IFN-alpha-2a inducing a sustained virological response in this HEV-positive and RNA-positive haemodialysis patient who had failed to be cleared of the virus after immunosuppressant withdrawal.

Background: In Goodpasture's disease, circulating autoantibodies bind to the noncollagenous-1 (NC1) domain of type IV collagen in the glomerular basement membrane (GBM). The specificity and molecular architecture of epitopes of tissue-bound autoantibodies are unknown. Alport's post-transplantation nephritis, which is mediated by alloantibodies against the GBM, occurs after kidney transplantation in some patients with Alport's syndrome. We compared the conformations of the antibody epitopes in Goodpasture's disease and Alport's post-transplantation nephritis with the intention of finding clues to the pathogenesis of anti-GBM glomerulonephritis., Methods: We used an enzyme-linked immunosorbent assay to determine the specificity of circulating autoantibodies and kidney-bound antibodies to NC1 domains. Circulating antibodies were analyzed in 57 patients with Goodpasture's disease, and kidney-bound antibodies were analyzed in 14 patients with Goodpasture's disease and 2 patients with Alport's post-transplantation nephritis. The molecular architecture of key epitope regions was deduced with the use of chimeric molecules and a three-dimensional model of the alpha345NC1 hexamer., Results: In patients with Goodpasture's disease, both autoantibodies to the alpha3NC1 monomer and antibodies to the alpha5NC1 monomer (and fewer to the alpha4NC1 monomer) were bound in the kidneys and lungs, indicating roles for the alpha3NC1 and alpha5NC1 monomers as autoantigens. High antibody titers at diagnosis of anti-GBM disease were associated with ultimate loss of renal function. The antibodies bound to distinct epitopes encompassing region E(A) in the alpha5NC1 monomer and regions E(A) and E(B) in the alpha3NC1 monomer, but they did not bind to the native cross-linked alpha345NC1 hexamer. In contrast, in patients with Alport's post-transplantation nephritis, alloantibodies bound to the E(A) region of the alpha5NC1 subunit in the intact hexamer, and binding decreased on dissociation., Conclusions: The development of Goodpasture's disease may be considered an autoimmune "conformeropathy" that involves perturbation of the quaternary structure of the alpha345NC1 hexamer, inducing a pathogenic conformational change in the alpha3NC1 and alpha5NC1 subunits, which in turn elicits an autoimmune response. (Funded by the National Institute of Diabetes and Digestive and Kidney Diseases.), (2010 Massachusetts Medical Society)

Epstein syndrome (ES) is an autosomal dominant hereditary disease characterized by hereditary nephritis, sensory deafness, and thrombocytopenia. We herein report the case of a 20-yr-old man with ES who underwent ABO blood type-incompatible living-donor kidney transplantation from his mother. He was given platelet transfusion, and his pre-operative number of platelets were 108 x 10(3)/microL. After transplantation, urine output and the decrease in serum creatinine (sCr) were within the acceptable ranges. On the seventh post-operative day (POD), sCr had risen and urine output decreased. Anti-type A antibody rapidly elevated from <2 times (x2) just before transplantation to 64 times (x64), and the patient required hemodialysis again. Resistance index (RI) by ultrasound increased from an average of 0.5 approximately 0.6 on POD 1 to an average of 0.7 approximately 0.8 on POD 7. However, several biopsies (POD 4, 7, and 10) showed no obvious findings of acute rejection except for intense C4d deposition. Because acute antibody-mediated rejection was not completely ruled out, he was treated with methyl-prednisolone pulse therapy, plasma exchange, cyclophosphamide, and immunoglobulin. Regardless, his titer of anti-type A antibody was still high, and he still presented oliguria. We performed an emergent splenectomy. Consequently, the levels of anti-type A antibody decreased, the RI also dropped to an average of 0.6. However, on POD 19 and 25 (platelets were 27 x 10(3)/microL and 36 x 10(3)/microL), he developed a massive intraperitoneal hematoma around the graft and region of the removed spleen, which pushed the graft out and caused acute tubular necrosis, resulting in anuria. The RI rose to an average of 0.8 approximately 1.0 after these episodes. He also experienced bleeding from a duodenal ulcer on POD 21. However, his renal function has fully recovered after acute hemodialysis for 35 d. The latest sCr was 1.5 mg/dL with a recovery in RI to 0.6. Although his platelet count was maintained at a minimum of 50 x 10(3)/microL, he had several severe bleeding episodes, concluding that sufficient platelets are necessary after transplantation in ES.

Alport's syndrome (Haemorrhagic Familial Nephritis) is a rare syndrome. It encompasses a group of heterogeneously inherited disorders involving the basement membrane of the kidney frequently involving the cochlea and the eye. We describe here the detailed ocular findings and the systemic problems of a case of Alport's syndrome in a 30 years male from Nepal. The current understanding of the clinical features and aetiopathogenesis are also discussed.

Alport Syndrome (AS) is an important hereditary disorder affecting the glomerular basement membrane. Diagnosis of AS is based on the presence of hematuric nephropathy, renal failure, hearing loss, ocular abnormalities and changes in the glomerular basement membrane of the lamina densa. The aims of this case report were to show the changes in the gingival tissues in a patient with AS under therapy with cyclosporin-A after renal transplantation and to discuss the possible role of type IV collagen in gingival basal lamina as an alternative approach for the diagnosis of AS. A 20-year-old male patient with AS underwent periodontal therapy including a series of gingivectomy surgeries. Gingival samples obtained during the second surgery were examined histopathologically and by transmission electron microscopy for further pathological examination. Gingivectomy procedures have been performed every 6 months over the last 4 years. The excessive and fibrous gingival enlargements resulted in migration of the anterior teeth, but no alveolar bone loss occurred. This is the first report to demonstrate the possible changes in the gingival tissues caused by AS. It is suggested that gingival biopsy can be an initial diagnostic tool instead of renal or skin biopsies. Proper dental and periodontal care and regular visits to the dentist could provide limited gingival hyperplasia to patients with AS.

Patients with Alport syndrome progressively lose renal function as a result of defective type IV collagen in their glomerular basement membrane. In mice lacking the alpha3 chain of type IV collagen (Col4A3 knockout mice), a model for Alport syndrome, transplantation of wild-type bone marrow repairs the renal disease. It is unknown whether cell-based therapies that do not require transplantation have similar potential. Here, infusion of wild-type bone marrow-derived cells into unconditioned, nonirradiated Col4A3 knockout mice during the late stage of disease significantly improved renal histology and function. Furthermore, transfusion of unfractionated wild-type blood into unconditioned, nonirradiated Col4A3 knockout mice improved the renal phenotype and significantly improved survival. Injection of mouse and human embryonic stem cells into Col4A3 knockout mice produced similar results. Regardless of treatment modality, the improvement in the architecture of the glomerular basement membrane is associated with de novo expression of the alpha3(IV) chain. These data provide further support for testing cell-based therapies for Alport syndrome.

A 27-year-old female patient reported a variable but unsatisfactory visual acuity which had persisted for several years. The patient had been dependent on dialysis from the age of 14 years old and from then on also needed a hearing aid. A kidney had been transplanted 5 years ago. The diagnosis was anterior lenticonus due to Alport syndrome.

A patient developed anaphylactic shock after a heparin dosage during an operation to make inner shunt for chronic renal failure of Alport syndrome. The operation was canceled and the patient was admitted to the ICU with tracheal intubation. He was extubated safely on the fifth postoperative day, but he lost the sense of smell from the day after. Abnormality of the nasal mucosa was not recognized. The smell disorder improved slowly in three or four weeks. Anosmia after anaphylactic shock is very rare, but we should be careful for this complication after anaphylactic shock.

We report the ocular manifestations of Alport syndrome and the surgical results in 4 patients. All 4 patients had anterior lenticonus; 2 also had posterior lenticonus in both eyes, 3 had flecked retina, and 1 had posterior polymorphous dystrophy. In both eyes of the 4 patients, phacoemulsification with intraocular lens (IOL) implantation was performed to treat anterior and posterior lenticonus. The postoperative visual acuity was excellent in all patients. We recommend phacoemulsification with IOL implantation as a safe and effective procedure in patients with lenticonus secondary to Alport syndrome.