Transplant with fsgs?

Im a 37 yr old male with FSGS found out I had it in 2000 started PD in July 2006 my doctors tell me I have a real good chance for a fast transplant but the more I read up on FSGS just about every thing I’ve read says it just about always come back and they have to have another transplant.Is this true and if so what % rate does the FSGS come back ? If so I have a hard time dealing with it just knowing someone is giving me a kidney knowing that the FSGS could come back and do this all over agian.My social worker I deal with is great and really listens to me but I would like to hear some other people with this to see what they think.
Thanks for looking

Hi Jammar, and welcome to Home Dialysis Central. This forum is for home dialysis, not transplant. But–since you’re new, and since I already did a bit of homework on this for the dialysis_support listserv, I’ll repost what I found, and hopefully you’ll find it helpful. I hope so.

I’m NOT a doctor, but I did a search of the published medical literature. (NOTE: This was not a systematic review, just a quick search of the most recent papers). The recurrence rate for FSGS and other glomerular diseases, can be pretty high: from about 20% (with FSGS the most likely type to recur) in one study to 34% in another, to about 66% in a third. None of these studies was large, so it’s hard to say what the “real” rate is.
– If your progression to renal failure was “rapid” (sorry, not defined), the risk is higher.
– If it was “familial” it is much lower (vs. if it is “sporadic”).
– If you are younger than 15 when the disease starts, the risk of recurrence is higher

There seems to be some evidence in small studies that getting plasmapheresis treatments to remove circulating FSGS permeability factor (FSPF) BEFORE a transplant can help reduce the risk of recurrence.

Below are some of the studies I found:

Transplant Proc. 2006 Mar;38(2):470-2.
Recurrent glomerular diseases after renal transplantation.
Karakayali FY, Ozdemir H, Kivrakdal S, Colak T, Emiroglu R, Haberal M. Department of General Surgery, Baskent University, Faculty of Medicine, Ankara, Turkey.

INTRODUCTION: Recurrent glomerular diseases are important causes of graft dysfunction after renal transplantation. As the outcomes of transplantation continue to improve, the problem of recurrent diseases in the transplanted kidney have become evident. The purpose of our study was to determine the risk factors for and the incidence of recurrence in the posttransplant period as well as their impact on graft survival rates. METHOD: We retrospectively analyzed 49 patients with glomerular diseases due to membranoproliferative glomerulonephritis (n = 26); focal segmental glomerulosclerosis (FSGS, n = 1 8); and systemic lupus erythematosus (n = 5). The mean follow-up was 9.5 years. RESULTS: Recurrent disease was detected in 30 of 49 patients after a mean posttransplant follow-up of 28.1 months (range = 1 to 157) and their average graft survival was 41.3 months. Nineteen patients were recurrence-free with a mean graft survival of 79.4 (range = 15 to 158) months (P < .05). One patient with FSGS, showed disease-recurrence in her third transplant after having experienced recurrences in the former grafts. In all six patients with HLA haplotype B8, recurrence was observed at a mean of 19.5 +/- 9.8 months. The only risk factor that was identified was this HLA haplotype. CONCLUSION: Recurrent disease a significant problem after renal transplantation is associated with decreased graft survival. The donor HLA type may be associated with risk, which should be clearly discussed with both the living donor and the recipient candidate.

2: Nephrol Dial Transplant. 2006 Apr;21(4):1053-9. Epub 2005 Dec 19.
Risk factors and outcome of focal and segmental glomerulosclerosis
recurrence in adult renal transplant recipients.
Pardon A, Audard V, Caillard S, Moulin B, Desvaux D, Bentaarit B, Remy P, Sahali D, Roudot-Thoraval F, Lang P, Grimbert P.
Department of Nephrology and Transplantation, Hopital Henri Mondor, Creteil, France.

BACKGROUND: Recurrence of nephrotic syndrome (NS) after renal transplantation for primary focal segmental glomerulosclerosis (FSGS) is a frequent and still unpredictable complication. However, risk factors for recurrence have not yet been clearly identified. METHODS: Data from 33 patients who underwent 35 renal transplantations for FSGS in two French centres are reported. RESULTS: Recurrent NS occurred in 12 transplant recipients (34%). A significantly higher number of patients in the group with recurrence (R group) compared with the group without recurrence (NR group) received cyclosporine for FSGS treatment before transplantation (83.3% vs 43.4%, P<0.02). Donors of R group recipients were significantly older than those of the non-NR group recipients (42.8 years vs 35 years, P<0.05). A higher number of patients from the R group required post-transplantation dialysis (33.3% vs 17.4%, P = 0.002). Surprisingly, acute rejection occurred more frequently in patients of the NR group compared with the R group, although the difference was not significant. Among the 12 patients with NS relapse, 9 were treated with plasmapheresis. Graft loss related to recurrence occurred in 6 cases. The 5-year graft survival was significantly lower in patients with recurrent NS compared with patients without recurrence (57% vs 82%, P<0.001). CONCLUSION: This study confirms the benefit to identify in the future clinical or biological predictive risk factors for NS recurrence after renal transplantation. It also indicates that donor age is a reliable risk factor for recurrence in adult recipients and suggests for the first time a possible opposite relationship between recurrent FSGS and acute rejection.

3: Am J Transplant. 2005 Dec;5(12):2907-12.
Preemptive plasmapheresis and recurrence of FSGS in high-risk renal
transplant recipients.
Gohh RY, Yango AF, Morrissey PE, Monaco AP, Gautam A, Sharma M, McCarthy ET, Savin VJ.
Division of Renal Diseases, Department of Medicine, Brown University School of Medicine, Providence, RI, USA. <mailto>

Recurrent focal segmental glomerulosclerosis (FSGS) following transplantation is ascribed to the presence of a circulating FSGS permeability factor (FSPF). Plasmapheresis (PP) can induce remission of proteinuria in recurrent FSGS. This study addressed the efficacy of pre-transplant PP in decreasing the incidence of recurrence in high-risk patients. Ten patients at high-risk for FSGS recurrence because of rapid progression to renal failure (n = 4) or prior transplant recurrence of FSGS (n = 6) underwent a course of 8 PP treatments in the peri-operative period. Recurrences were identified by proteinuria >3 g/day and confirmed by biopsy. Seven patients, including all 4 with first grafts and 3 of 6 with prior recurrence, were free of recurrence at follow-up (238-1258 days). Final serum creatinine in 8 patients with functioning kidneys averaged 1.53 mg/dL. FSGS recurred within 3 months in 3 patients, each of whom had lost prior transplants to recurrent FSGS. Two of these progressed to end-stage renal disease (ESRD) and the third has significant renal dysfunction. Based on inclusion criteria, recurrence rates of 60% were expected if no treatment was given. Therefore, PP may decrease the incidence of recurrent FSGS in high-risk patients. Definitive
conclusions regarding optimal management can only be drawn from larger, randomized, controlled studies.

4: Pediatr Nephrol. 2005 Jul;20(7):994-7. Epub 2005 May 12.
Complete remission of post-transplant FSGS recurrence by long-term
Haffner K, Zimmerhackl LB, von Schnakenburg C, Brandis M, Pohl M.
Department of Pediatrics and Adolescent Medicine, Albert-Ludwigs-University, Mathildenstrasse 1, 79106 Freiburg, Germany.

Focal segmental glomerulosclerosis (FSGS) is known to recur in approximately 30% of renal allografts with graft loss in about half of these cases. The exact etiology remains unclear, though a putative circulating permeability factor or loss of inhibitory substances is being discussed. Different therapeutic approaches have been used. We report on a 10-year-old Arabian boy with a recurrence of FSGS immediately after transplantation. In addition to intensifying immunosuppressive therapy with high-dose cyclosporin A and cyclophosphamide, plasmapheresis was initiated and remission was achieved after 8 months. Three weeks after cessation of plasmapheresis a relapse occurred. Plasmapheresis was resumed and remission was achieved again after four additional sessions. The interval between plasmapheresis treatments was then gradually increased and fourteen months after transplantation plasmapheresis was stopped again. Since then (1.5 years after cessation of treatment) the patient has been in complete remission without any
further episode of proteinuria. In conclusion, complete and sustained remission with stable renal function was achieved in our patient by long-term plasmapheresis in combination with intensified immunosuppression. Therefore, continuation of plasmapheresis treatment should be considered even in the situation of initial non-response.

5: Am J Transplant. 2005 Jun;5(6):1179-85.
Comment in:
* Am J Transplant. 2005 Oct;5(10):2594; author reply 2595.
New insights into the pathogenesis and the therapy of recurrent focal
Vincenti F, Ghiggeri GM.
Kidney Transplant Service, University of California, San Francisco,
USA. <mailto>

Recurrent focal glomerulosclerosis (FSGS) in renal allografts has remained a frustrating and enigmatic disease. Recent studies on gene mutations encoding podocin and other components of the slit-diaphragm in patients with native kidney nephrotic syndrome have underscored the heterogenecity of the idiopathic form of FSGS. While familial FSGS rarely recurs following transplantation, the sporadic variety of FSGS is associated with a 30% recurrence rate. The patients with the sporadic variety of FSGS who have homozygous or complex heterozygous podocin mutations have a low recurrence rate. In the other patients with sporadic FSGS, a more complex and likely multifactorial etiology accounts for the recurrence of FSGS. The role of CD80 expression on podocytes is intriguing but requires confirmation in kidney biopsies of patients with recurrent FSGS. Recent findings on podocin genomics, the permeability factor and CD80 expression may ultimately lead to a better understanding of recurrent FSGS as well as a more effective approach to its prevention and treatment.

Dori thanks for the gave me it helped alot.Since I’ve been on PD Dialysis I have been trying to find out all I can on what made me have to start dialysis (FSGS) and and all the things that maybe a head of me to come. I pray that I will not have to be on dialysis though the rest of my life but if so at least it’s a life! :smiley: Thanks agian and take care.

Thanks for those studies ,Dori. You are a gem and it gives us FSGS’ers some hope for a successful transplant. (:

Hi, I lost my kidneys to FSGS and recived a kidney transplant that lasted 12 years. I am lost the kidney due to scaring caused by long term prograf use, but i still thing I had a really good result. There is hope,

My son has FSGS and has had a transplant in 2001. He had recurrence in his transplant within 24 hours but he had plasmapherisis treatments done which helped control the spilling of protein. His kidney lasted 5 years and his lifestyle was easier although the treatments were a pain for him. We are in the process of having him re-transplanted but we are fully aware that he will need plasmapheresis before and after the transplant. After a few months the plasmapheresis treatments became monthly for him and his lifestyle was a lot better for a kid. I feel the more you learn the better it is because i learned more through experience with him and everything came as a shock, without being aware of what could happen. Now we know and we feel more prepared, which helps me just think about the important things such as making him as comfortable as possible and being positive.

I too have FSGS and am Pre Dialysis and have been on cyclosporine since May 2006. Up until December It was helping me control the protein loss very well but in january 07 It started to reverse and stop helping. Doctor wants me to switch from cyclosporine to celcept but I haven’t made up my mind yet.

I just found out in Feb 2011 that I have had FSGS since I was 4 years old, if not younger.( I am now 30) I had a kidney/pancreas transplant 2 years ago and just found out this past week that my new kidney is failing because the FSGS has attacked it. My transplanted kidney is operating at about 30% right now. I was just wondering if they will make me go through another “work up” and get all that bloodwork done again, and if I would have to talk to a psychologist again to make sure I’m mental strong enough to deal with this. I also wondered if things were different when it came time to make a decision about dialysis. When my kienys were failing before my first transplant, I was told I wouldn’t have to start dialysis until my function dropped to 10%, I was just wondering if that was still the number they go by now that I am a transplant patient and getting ready for another transplant. Too soon to say yet when the transplant will be, as I don’t know how long my kidneyswill last at 30%. If anyone has any info on it for me, that would be great! Thanks!

It sounds as if you’ve been through a lot! I’m so sorry to hear that the FSGS is attacking your kidney. There is a recent set of studies that have found that there is no benefit (and may even be some harm) to starting dialysis before the GFR drops to 6-9%, unless there are symptoms. So, if you feel pretty good, waiting until it’s 9 or below makes sense. The best known of these studies was called the IDEAL study:

Contrib Nephrol. 2011;171:1-9. Epub 2011 May 23.
Outcomes of patients with planned initiation of hemodialysis in the IDEAL trial.
Collins J, Cooper B, Branley P, Bulfone L, Craig J, Fraenkel M, Harris A, Johnson D, Kesselhut J, Li JJ, Luxton G, Pilmore A, Tiller D, Harris D, Pollock C.
Department of Renal Medicine, Auckland City Hospital, Auckland, New Zealand.


In clinical practice there is considerable variation in the timing of initiation of dialysis. The IDEAL trial (Initiating Dialysis Early and Late study) showed that planned early initiation of dialysis in patients with stage 5 chronic kidney disease (CKD) was not associated with an improvement in clinical outcome, but was associated with increased costs. The predominant dialysis modality worldwide is hemodialysis (HD). This subanalysis of the IDEAL trial examined whether the timing of the initiation of dialysis in those who had chosen HD influenced survival and the occurrence of complications.

Patients on the IDEAL trial were older than 18 years and had progressive advanced CKD. They were randomly assigned to commence dialysis at an estimated glomerular filtration rate (eGFR) of 10-14 ml/min (early start) or when the eGFR was 5-7 ml/min (late start). The primary outcome was death from any cause.

Between 2000 and 2008, 362 of the 828 patients (43.7%) randomized in the trial planned to commence HD. 322 (88.9%) of these subsequently commenced HD and 17 (4.7%) commenced peritoneal dialysis, with a median time to the initiation of dialysis of 1.63 months in the early-start group and 6.93 months in the late- start group. During a median follow-up time of 3.81 years, 50 of 171 patients in the early-start group (29.2%) and 59 in the late-start group (30.1%) died (hazard ratio with early initiation=0.97: 95% CI: 0.66-1.41; p=0.86). There was no significant difference in the frequency of cardiovascular events, infections, or access-related events, but there was a significantly higher frequency of fluid and electrolyte events in the late-start group (p=0.02).

In this subanalysis of the IDEAL trial, patients commencing dialysis early with stage 5 CKD for whom the planned dialysis modality was HD did not have an improvement in survival or any reduction in most clinical outcomes apart from fluid and electrolyte events.

I would just quickly like to make everyone aware (if you are not already) that they think they have found the cause of fsgs…

I don’t know if this info comes too late for you, but perhaps a practical application can soon be implemented. There is real cause for hope!

Thanks, Moosemom! I hadn’t seen this, and it’s big news! Just in case the site takes down this article eventually, I’ve snagged it:

Nephrologists Discover Cause of Common Kidney Disease
Nephrologists at the Miller School have solved a decades-long search for the cause of a significant form of chronic kidney disease – focal segmental glomerulosclerosis (FSGS). Working with mouse models and a bank of patient samples, scientists have discovered the first circulating factor known to start the process leading to FSGS. The finding, a fundamental principle of the origin of kidney disease, is published in the July 31 edition of the journal Nature Medicine.

Jochen Reiser, M.D., Ph.D., professor and vice chair for research in the Department of Medicine and chief of the Division of Nephrology and Hypertension, and Changli Wei, M.D., Ph.D., assistant professor of medicine in the Division of Nephrology and Hypertension, led a team of international researchers and physicians in discovering that a soluble form of the urokinase plasminogen activator receptor (suPAR) is a factor in triggering glomerular kidney disease.

“This is truly monumental and a great team effort that paid off,” Reiser said, “because we can measure the amount of suPAR, and develop targeted treatments for that factor or prevent what it does to the kidney.”

Each kidney is made up of approximately one million glomeruli, specialized capillary beds that filter the blood. The glomeruli are composed of endothelial cells, a membrane and podocytes. The podocytes have cellular foot processes that are bridged by a slit diaphragm and that wrap around the glomerular blood vessels. Podocytes work as goalkeepers in the kidney, preventing protein from leaking into the urine. FSGS occurs due to a breakdown of podocytes, fusing them together, and allowing protein to infiltrate the urine leading to scarring of the kidney.

Focal segmental glomerulosclerosis is a common type of chronic kidney disease, with more than 5,000 new cases diagnosed each year. It often leads to end-stage renal disease, which affects approximately 20,000 people in the U.S. While podocyte gene defects are one cause, most cases have no known cause. FSGS shares similarities with diabetic nephropathy, which is often termed secondary FSGS and is the most common reason for end-stage renal disease. Reiser’s finding now explains possibly two-thirds of FSGS.

“This discovery is going to change the future of treating chronic kidney disease,” said Pascal J. Goldschmidt, M.D., Senior Vice President for Medical Affairs and Dean of the Miller School, and CEO of UHealth-University of Miami Health System. “By identifying the first circulating factor that triggers the switch for glomerular disease, Jochen and his team have ended a 40-year search by pinpointing how the kidney filtration system breaks down. Scientists around the world can now focus on developing targeted therapies to minimize that factor.”

In 2008, Reiser and Wei published another study in Nature Medicine demonstrating that urokinase receptor (uPAR) can be produced in the podocyte, activating the β3-integrin switch, a protein involved in cell signaling. Left in an active state, this switch begins to set the podocyte foot processes in motion, leading to the degradation of the filter barrier (proteinuria), eventually turning the glomeruli into scar tissue, leading to glomerular disease.

Clinical reports from nearly 40 years ago revealed that FSGS can recur within minutes of kidney transplantation, leading physicians to theorize that there were factors in the blood that were degrading the kidney. The hunt for the FSGS factor was on, in an effort to discover one of nephrology’s biggest secrets and to help high-risk patients including children, whose recurrence of FSGS after transplantation can be as high as 86 percent.

“There is a clear need to discern what’s causing this disease to recur so quickly in so many patients,” Wei said. “Finding the factor will not only improve post-transplant FSGS but will also teach us the reason for pre-transplant FSGS as current therapies are limited, unspecific and minimally effective.”

Over the past decade, Reiser discovered that podocytes were motile cells, and thus the filter barrier in the kidney was a dynamic rather than a static structure. Following this hypothesis, he began looking for activators of podocyte motility. He and his colleagues used genetic and molecular tools to discover, in a series of high impact publications including this paper’s finding, that blood suPAR or podocyte uPAR are what’s activating the β3-integrin switch in the podocyte. Too much suPAR in the blood and the switch remains active, degrading the podocyte and the kidney filter.

The findings were validated in kidney transplant patient samples. Reiser, director of the Peggy and Harold Katz Family Drug Discovery Center, points out the benefit of this discovery to patients: “This could potentially explain fundamental pathologic issues that occur in chronic kidney diseases.” Those with native kidney disease can now be tested for suPAR levels and provided therapies that will aim to reduce that level. Similarly, transplant patients would have elevated suPAR levels reduced before surgery, ensuring a lower risk for recurrent disease. Reiser says identifying suPAR and the β3-integrin switch opens the door to general principles for other glomerular diseases such as diabetic nephropathy.

Wei is hopeful their five-year-long study will lead to new treatments. “Patients with FSGS and other glomerular diseases will benefit from our finding very soon.”