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Keywords:

  • Focal segmental glomerulosclerosis;
  • kidney transplantation;
  • plasma pheresis

Abstract

  1. Top of page
  2. Abstract
  3. Introduction
  4. Methods
  5. Results
  6. Discussion
  7. Acknowledgments
  8. References

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.


Introduction

  1. Top of page
  2. Abstract
  3. Introduction
  4. Methods
  5. Results
  6. Discussion
  7. Acknowledgments
  8. References

Primary focal segmental glomerulosclerosis (FSGS) is manifested by steroid-resistant nephrotic syndrome, microscopic hematuria and hypertension. Renal insufficiency may be present at the time of diagnosis. Many patients with FSGS have a limited response to conventional therapy and experience progressive deterioration of renal function to end-stage renal disease (ESRD) (1). FSGS may recur following transplantation and is characterized by proteinuria, hypertension and allograft dysfunction (2–4). Recurrence may be evident within hours after transplantation (5,6) and occurs within the first year in about 80% of affected patients (6). Among patients with recurrent FSGS, approximately half lose their allograft because of recurrent disease, and the incidence of early graft dysfunction and rejection is reportedly increased as well (2–4). FSGS recurs in 20–30% of first transplants in patients with renal failure due to FSGS (7–15) and in more than 80% of subsequent renal grafts after post-transplant recurrence and graft loss (13,16). Recurrence has been identified as the third most frequent cause of allograft failure in a cohort of kidney transplant recipients in Australia (17).

The rapid recurrence of proteinuria following transplantation supports the notion that a causative factor responsible for inducing glomerular permeability is present in the circulation of some individuals. The salutary effect of plasmapheresis (PP) and immunoabsorption with protein A in inducing remission of proteinuria provides additional evidence for a circulating FSGS permeability factor (FSPF) (8,18–20). Although progress has been made toward the molecular identification of FSPF, its exact structure remains elusive. The putative molecule identified by Savin and colleagues is a small glycoprotein, which is present in plasma at very low concentrations and may be protein bound under some conditions (21,22). In some instances, inhibitory substances present in normal serum may play a role in protecting glomeruli from proteinuria (23,24).

Savin and colleagues have developed an in vitro assay for permeability activity (25) and have used this assay to define the effect of FSGS serum on the permeability to albumin (Palb) of glomeruli from normal rats (21). Savin and others have shown a significant association between Palb activity and the likelihood of recurrence of FSGS (19,21).

Removal of FSPF seems to be the mechanism responsible for the success of plasmapheresis (PP) in the therapy of recurrent FSGS. Palb activity is reduced by PP or immunoadsorption (21). Several centers have reported the success of PP or immunoadsorption in inducing remission in the majority of patients treated within 2 weeks of relapse (8,9,19,20). This response suggests that the preemptive treatment of high-risk individuals with PP in the pre-transplant or peri-operative period may alter or even prevent disease recurrence. A number of centers have used this maneuver in individual patients but the data have not been collated and no trials have been designed to address the efficacy of preemptive PP. We initiated a study to test the hypothesis that aggressive pre-transplant PP prevents recurrence of primary FSGS and increases long-term allograft survival.

Methods

  1. Top of page
  2. Abstract
  3. Introduction
  4. Methods
  5. Results
  6. Discussion
  7. Acknowledgments
  8. References

Patient selection, allograft source and immunosuppression

Nineteen patients with the primary diagnosis of FSGS were transplanted during the study period, 1999–2003. Inclusion criteria were biopsy-proven FSGS, ESRD within 3 years of diagnosis or advanced azotemia at presentation or prior allograft loss due to recurrent FSGS. Both children and adults were eligible. Ten patients met the study criteria and each agreed to participate. The trial was approved by the local institutional review board and informed consent was obtained from each participant or legal guardian. All 4 patients with rapid progression and 5 of 6 patients undergoing re-transplantation had Palb≥ 0.6. Palb was not used in selecting patients for this study.

Five allografts were from cadaver and 5 from living donors. All patients were treated with induction therapy by institutional protocol. Rabbit-ATG was used as induction for cadaver donor recipients and basiliximab for living donor recipients. Maintenance immunosuppression consisted of triple drug therapy including tacrolimus, mycophenolate mofetil and prednisone. Tacrolimus doses were adjusted to maintain trough drug levels of 8–10 ng/mL in the first 6 post-transplant months and 5–8 ng/mL thereafter. Prednisone doses were weaned to 10 mg/day by 6 months.

Palb assay

The principles of the in vitro assay, the methodology and preparation of patients' sera for the assay have been described previously (25). To calculate Palb, glomeruli were isolated from Sprague-Dawley rats by standard sieving techniques in an isolation medium containing an oncotic agent, bovine serum albumin (BSA, 4g/dL) and incubated at 37°C with a diluted sample of serum (2% vol/vol) from a study participant. An oncotic gradient across the capillary wall was caused by replacing the medium with fresh medium with BSA (1g/dL) and the resulting expansion of glomerular capillaries was measured using videomicroscopy. An increase in albumin permeability results in a decrease in effective oncotic gradient and in diminished glomerular capillary expansion (ΔV). Palb was calculated as 1 – (σalb) where σalb= (ΔVexperimental/ΔVcontrol). Palb values for each specimen were reported as the mean of the values of 5 or more glomeruli. Palb is a dimensionless variable with a minimum of zero for normal glomeruli and a maximum of 1.0 for glomeruli that are freely permeable to albumin. Although Palb has a continuous distribution, 0.5 is used as a cut-off for ‘positivity’ in individual patients because 0.5 is the upper limit of the 95% confidence interval for patients with renal disease other than FSGS (21). Palb assays were performed prior to transplantation and before PP.

Protocol therapy

All study participants were subjected to a course of 8 PP (1 plasma volume/exchange) over a 2-week span in the immediate peri-operative period. Recipients of living donor kidneys initiated PP treatments 1 week before transplantation and completed their course at the end of the first post-operative week. Recipients of cadaver kidneys underwent initial PP within 24 h of implantation. Replacement fluid consisted of one plasma volume of 3.33% albumin solution, delivered by the sequential administration of 0.9% saline and 5% albumin in a 1:2 ratio. Anticoagulation consisted of acid-citrate dextrose A (Baxter anticoagulant citrate solution). Calcium supplementation was provided orally for patients exhibiting symptoms suggestive of hypocalcemia as chewable calcium carbonate or as calcium gluconate (10%) infused intravenously as part of the replacement fluid. No patients received plasma or intravenous immunoglobulin as replacement fluid.

Physiologic monitoring

Renal function was assessed by serum creatinine, blood urea nitrogen, urinalysis and 24-hour urine collections for protein. Disease recurrence was defined as proteinuria of >3 g/day following transplantation and a transplant biopsy showing podocyte foot process effacement with or without segmental sclerotic lesions. Rejection episodes were graded according to the Banff classification system. All patients had negligible urine outputs and insignificant levels of proteinuria prior to transplantation. No patient had previously undergone nephrectomy of his or her native kidneys.

Statistical analyses

Average values for parametric parameters were calculated and displayed in Tables 1 and 2. Values in the text are given as average ± standard deviation. Comparison between groups defined by nonparametric parameters were made using Fischer exact test. A p-value of <0.05 was accepted as significant.

Table 1.  Patient characteristics
Patient Sex Race Age DonorAllograft no. Palb
1FW45Cad20.61
2MW41Liv30.63
3MW28Liv10.97
4MW33Cad20.72
5FH46Liv10.96
6MH45Cad20.87
7FW33Liv10.94
8FW46Liv20.76
9FW9Cad20.30
10FH25Cad10.85
Table 2.  Patient outcomes
PatientFollow-up (days)Induction therapy*Current immuno-suppression** RecurrenceProtein-uria (g/day) RejectionSerum creatinine (mg/dL)
  1. *T = thymoglobulin; B = basiliximab.

  2. **T = tacrolimus; M = mycophenolate mofetil; P = prednisone.

11258TT/M/PN0.30N1.0
2980BT/M/PN0.19N1.1
3959BT/M/PN0.39Y1.8
4749TT/IY4.75N2.6
5735BT/M/PN0.81Y1.3
6699TR/I/PN0.39N2.0
7644BT/M/PN0.33N1.5
8962BT/I/PY37.1NHD
9238TT/M/PY7.5NHD
10287TT/M/PN0.59N0.9

Results

  1. Top of page
  2. Abstract
  3. Introduction
  4. Methods
  5. Results
  6. Discussion
  7. Acknowledgments
  8. References

During the study period (1999–2003), 299 kidney transplants were performed at Rhode Island Hospital. Nineteen (6.4%) carried the diagnosis of FSGS and 10 patients met the ‘high-risk’ clinical criteria to participate in the trial. All eligible patients agreed to enroll. Average age of participants was 35 ± 12 years (range, 9–46). Six were female. Six patients had lost a previous allograft due to recurrent disease. Five had 1 prior transplant; 1 had 2 prior transplants. Of these individuals, 3 (patients #4, #8, #9) had developed recurrent disease in a rapid (within the first year) and aggressive fashion in their previous allografts. Those individuals who did not meet the criteria for study participation (‘low-risk’ patients) did not undergo evaluation by the Palb assay or PP therapy. However, their renal function was followed during the study period. None of these ‘low-risk’ patients developed proteinuria >3 g/day and none had evidence of recurrent FSGS on allograft biopsy.

Patients tolerated the PP treatments without complications. One patient had delayed graft function (Patient #9). All patients achieved normal renal function after transplantation, as evidenced by a mean nadir serum creatinine of 1.3 ± 0.4 mg/dL. Patients were followed for a 751 ± 314 days following transplantation (range 238–1258 days). Renal biopsies were only performed on the basis of graft dysfunction (elevated serum creatinine, nephrotic range proteinuria); protocol biopsies were not performed.

Seven patients had an uncomplicated transplant course with no recurrence of proteinuria. These included the 4 patients with rapid progression and 3 of those with prior graft loss to FSGS. Graft function was excellent, with a serum creatinine of 1.26 ± 0.63 mg/dL at the end of the follow-up period. Average Palb for patients without recurrence was 0.83 ± 0.15 (range 0.61–0.97). Two patients without recurrence experienced late clinical rejection more than a year following transplantation. Rejection episodes were characterized by worsening renal function and were confirmed by renal biopsy. Histology demonstrated Banff IIA and Banff IB pathology, respectively. Each of these patients responded to bolus methylprednisolone therapy with return of allograft function to baseline. The presence of proteinuria was also monitored closely in those study patients without recurrence (Table 1). At 1 year, the average level of proteinuria in this subgroup was 429 ± 210 mg/day (range 190–800 mg/day).

Three patients had recurrence of proteinuria (4–10 g/24 hours) and biopsy findings of foot process fusion and, in some cases, glomerular scarring. Each of these had lost prior grafts to recurrence. Average Palb for patients with recurrence was 0.59 ± 0.26 (range 0.30–0.76). Each recurrence in the current study was diagnosed within the first 3 months of transplantation. Two patients with recurrence received cadaver organs and one a living-related allograft. One recurrence developed immediately post-transplant (patient #9). All 3 patients with recurrence were treated with an additional course of PP. Two patients had partial remissions (proteinuria <2 g/day). Patient #9 failed to respond to a repeated course of PP and proteinuria remained >20 g/day. Two patients with recurrence lost allograft function and returned to dialysis after 225 and 962 days, respectively. The remaining patient with recurrent disease has shown progressive deterioration in his renal allograft function during a follow-up of 749 days and remains nephrotic with a serum creatinine of 2.6 mg/dL.

All patients with recurrence in this study had lost prior allografts to recurrence, as had three of the seven who did not have recurrence p > 0.1 Fisher exact test). Age, race, sex, allograft source did not differ in patients with and without recurrence. Palb was >0.6 in 9/10 patients. This finding is consistent with the high incidence of Palb previously reported in patients with recurrence (26). There was no association between recurrence and acute rejection. These results are displayed in Tables 1 and 2.

Discussion

  1. Top of page
  2. Abstract
  3. Introduction
  4. Methods
  5. Results
  6. Discussion
  7. Acknowledgments
  8. References

Clinical features associated with recurrence of FSGS in initial transplants include an aggressive initial course of disease in the native kidney (renal failure within 3 years of onset), mesangial proliferation on biopsy and patient age less than 15 years (8,11,27). The use of living donor kidneys has been proposed as an additional risk factor for recurrence. However, this has not been confirmed by recent studies (6). Rather, the survival of a living donor and cadaveric transplants is about the same (5). Patients who experience graft rejection may also be at increased risk of recurrence (4). Palb > 0.5 has been suggested as an additional criterion to define risk (3,21).

The series of patients presented here is the first reported in which formal protocols for PP and immunosuppression were used in a prospective study of patients at high risk for recurrent FSGS. Six of the 10 patients studied had lost 1 or more prior transplants to recurrence and 4 had rapid progression to ESRD. Our hypothesis was that PP in the immediate pre- and peri-operative period would decrease the incidence and severity of post-transplant recurrence. This hypothesis was based on the success of post-transplant PP in inducing remission of proteinuria in recurrent FSGS and on anecdotal reports that suggested the potential for benefit of pre-transplant treatment. In our series, 50% of patients with prior recurrence and none of those with rapid progression recurred. Neither the source of the kidney nor the occurrence of rejection affected recurrence rate.

Two published series describe the outcome of transplantation in high-risk patients defined by criteria comparable to those in our study (3,27). Patients who received no specific therapy at the time of transplant had a recurrence rate of 61%. In patients who received multiple PP treatments, the recurrence rate was 33%. These results are summarized in Table 3. The recurrence rate of 30% after extensive PP in our series was comparable to the results of others and is lower than the recurrence rate described in untreated high-risk patients.

Table 3.  Outcomes in high-risk patients
Reference Pre-treatment PalbNo. of patientsNo. of recurrences % recurrences
  1. Data were abstracted from references as noted. Patients in Ref. 28 were divided according to whether they received no PP treatment at the time of transplantation or 2–3 treatments. Total number of patients and number with recurrence were calculated for those with no PP and for those who received any number of PP treatments. Recurrence differed between no PP and 2 or more PP, chi-squared = 4.755, p < 0.05.

Dall'Amico (3)NonePalb < 0.512433
 Palb > 0.5131185
Ohta (28)NoneNA6467
TOTALNone 311961
Ohta (28)2–3 PPNA15533
Gohh (this series)8 PPPalb < 0.511100
 Palb > 0.59222
TOTAL2–8 PP 25832

The functional assay for albumin permeability (Palb) in isolated rat glomeruli permits measurement of the capacity of serum or plasma to alter the permeability barrier. Permeability activity resulting in Palb > 0.5 is present in about 30% of patients with FSGS in native kidneys and in nearly all of those with recurrent FSGS who have been studied (3, 21). Palb activity is transiently decreased by PP (21). High permeability activity in pre-transplant serum predicts post-transplant recurrence in patients who have already reached ESRD due to FSGS (9). The presence and clinical significance of Palb in FSGS has been confirmed by the observation that FSGS recurred in 11/13 children with Palb≥ 0.6 and in 4/12 children with Palb≤ 0.5 (3). Palb activity varies among FSGS patients and the highest Palb levels (≥0.80) have been associated with a greatest recurrence risk following transplantation (>90%) (19,28). All but 1 patient in our study had high Palb activity. The patient with low Palb had lost a prior transplant to recurrence and had no remission of proteinuria after additional PP. These findings are consistent with the presence of a different mechanism of recurrence.

PP and plasma adsorption on protein A or anti-human immunoglobulin columns markedly reduce protein excretion or even induce complete remission in some patients with recurrent FSGS (8,9,19,20,29–31). Treatment is most effective when it is started soon after the appearance of proteinuria. Remission may result from the removal of plasma permeability factor(s). The effect of extracorporeal therapy is often transient, as many patients relapse when PP is discontinued. It remains to be established whether PP alters the long-term prognosis for graft outcome. Immunosuppression with drugs that inhibit T lymphocytes and pulse methylprednisolone has also been used in recurrent FSGS but is not generally effective (17,29). Treatment with cyclosporine (CsA) may decrease proteinuria in recurrent as well as primary FSGS (31,32). CsA has a direct protective effect on Palb during in vitro testing of sera in FSGS (33). However, routine inclusion of CsA in immunosuppressive regimens does not prevent recurrence (32–34). The effect of tacrolimus or sirolimus on FSGS recurrence is unknown. Cyclophosphamide combined with PP has also induced remission in a few patients with post-transplant FSGS (35) but no formal trial has been reported.

The present study was designed to examine the hypothesis that PP prior to or immediately after transplantation modifies the post-transplant course of FSGS. We recognized that the number of patients available to us would not provide a statistically significant result unless the therapy was universally effective. Results confirm the feasibility of identifying high-risk patients and of carrying out the required treatments and follow-up. In addition, our results show that it is feasible to perform pre-transplant PP without incurring increased risk for infection or bleeding. Our findings of recurrence in only 50% of patients with prior FSGS recurrence and in none of those with rapid progression provide encouragement for further exploration of pre-transplant treatment.

We conclude that preemptive PP may provide some protection from recurrence of FSGS after renal transplantation. Palb activity is associated with clinical parameters that define risk for recurrence but is absent in some patients who have recurrence. This finding is consistent with the presence of another mechanism for recurrence in addition to the circulating permeability factor. A larger trial will be required to define the efficacy of interventions before and immediately after transplant in FSGS.

Acknowledgments

  1. Top of page
  2. Abstract
  3. Introduction
  4. Methods
  5. Results
  6. Discussion
  7. Acknowledgments
  8. References

This study was supported by grants from the NIH, RO1DK 43752 (Savin) and KO8 DK02587 (McCarthy).

References

  1. Top of page
  2. Abstract
  3. Introduction
  4. Methods
  5. Results
  6. Discussion
  7. Acknowledgments
  8. References
  • 1
    Korbet SM. Primary focal segmental glomerulosclerosis. J Am Soc Nephrol 1998; 50: 13331340.
  • 2
    Cameron JS. Recurrent renal disease after renal transplantation. Curr Opin Nephrol Hypertens 1994; 3: 602607.
  • 3
    Dall'Amico R, Ghiggeri G, Carraro M, Artero M et al. Prediction and treatment of recurrent focal segmental glomerulosclerosis after renal transplantation in children. Am J Kidney Dis 1999; 34: 104855.
  • 4
    Kim EM, Striegel J, Kim Y, Matas AJ, Najarian JS, Mauer SM. Recurrence of steroid-resistant nephritic syndrome is associated with increased acute renal failure and acute rejection. Kidney Int 1994; 45: 14401445.
  • 5
    Baum MA, Stablein DM, Panzarino et al. Loss of living donor renal allograft survival advantage in children with focal segmental glomerulosclerosis. Kidney Int 2001; 59: 328333.
  • 6
    Briggs JD, Jones E, on behalf of the scientific advisory board of the ERA-EDTA Registry. Recurrence of glomerulonephritis following renal transplantation. Nephrol Dial Transplant 1999; 14: 564565.
  • 7
    Holgado R, Del Castillo D, Mazuecos A et al. Long-term outcome of focal segmental glomerulosclerosis after renal transplantation. Transplant Proc 1999; 31: 23042305.
  • 8
    Dantal J, Baatard R, Hourmant M et al. Recurrent nephrotic syndrome following renal transplantation in patients with focal glomerulosclerosis: A one-center study of plasma exchange effects. Transplantation 1991; 52: 827831.
  • 9
    Artero ML, Sharma R, Savin VJ, Vincenti F. Plasmapheresis reduced proteinuria and serum capacity to injure glomeruli in patients with recurrent focal glomerulosclerosis. Am J Kidney Dis 1994; 23: 574581.
  • 10
    Carraro M, Caridi G, Bruschi M et al. Serum glomerular permeability activity in patients with podocin mutations (NPHS2) and steroid-resistant nephrotic syndrome. J Am Soc Nephrol. 2002; 13(7): 19461952.
  • 11
    Cheigh JS, Mouradian J, Susin M et al. Kidney transplant nephrotic syndrome: Relationship between allograft histopathology and natural course. Kidney Int 1980; 18: 358365.
  • 12
    Pinto J, Lacerda G, Cameron JS et al. Recurrence of focal and segmenal glomerulosclerosis in renal allografts. Transplantation 1932; 32: 8389.
  • 13
    Tejani A, Stablein DH. Recurrence of focal and segmental glomerulosclerosis posttransplantation: A special report of the North American Pediatric Renal Transplant Cooperative Study. J Am Soc Nephrol 1992; 2(Suppl 12): S258263.
  • 14
    Lewis EJ. Recurrent focal sclerosis after renal transplantation. Kidney Int 1982; 22: 315323.
  • 15
    Abbott KC, Sawyers ES, Oliver JD et al. Graft loss due to recurrent focal segmental glomerulosclerosis in renal transplant recipients in the United States. Am J Kidney Dis 2001; 37: 366373.
  • 16
    Striegel JE, Sibley RK, Fryd DS, Mauer SM. Recurrence of focal segmental sclerosis in children following renal transplantation. Kidney Int Suppl 1986; 19: S4450.
  • 17
    Briganti EM, Russ GR, McNeil JJ et al. Risk of renal allograft loss from recurrent glomerulonephritis. New Eng J Med 2002; 347: 103109.
  • 18
    Artero M, Biava C, Amend W, Tomlanovich S, Vincenti F. Recurrent focal glomerulosclerosis: Natural history and response to therapy. Am J Med 1992; 92: 375383.
  • 19
    Dantal J, Bigot E, Bogers W et al. Effect of plasma protein adsorption on protein excretion in kidney transplant recipients with recurrent nephrotic syndrome. N Engl J Med 1994; 330: 714.
  • 20
    Dantal J, Godfrin Y, Koll R et al. Antihuman immunoglobulin affinity immunoadsorption strongly decreases proteinuria in patients with relapsing nephrotic syndrome. J Am Soc Nephrol 1998; 9: 17091715.
  • 21
    Savin VJ, Artero M, Sharma R et al. Circulating factor associated with increased glomerular permeability to albumin in recurrent focal segmental glomerulosclerosis. N Engl J Med 1996; 334: 878883.
  • 22
    Sharma M, Sharma R, McCarthy ET, Savin VJ. The focal segmental glomerulosclerosis permeability factor: Biochemical characteristics and biological effects. Exp Biol Med (Maywood) 2004; 229: 8598.
  • 23
    Sharma R, Sharma M, McCarthy ET, Ge XL, Savin VJ. Components of normal serum block the focal segmental glomerulosclerosis factor activity in vitro. Kidney Int 2000; 58(5): 19731979.
  • 24
    Candiano G, Musante L, Carraro M et al. Apolipoproteins prevent glomerular albumin permeability induced in vitro by serum from patients with focal segmental sclerosis. J Am Soc Nephrol 2001; 12(1): 143150.
  • 25
    Savin VJ, Sharma R, Lovell HB, Welling DJ. Measurement of albumin reflection coefficient in isolated rat glomeruli. J Am Soc Nephrol 1992; 3: 12601269.
  • 26
    Savin VJ, Artero M, Sharma R et al. Circulating factor associated with increased glomerular permeability to albumin in recurrent focal segmental glomerulosclerosis. N Engl J Med 1996; 334: 878883.
  • 27
    Ohta T, Kawaguchi H, Hattori M et al. Effect of pre- and postoperative plasmapheresis on posttransplant recurrence of focal segmental glomerulosclerosis in children. Transplantation 2001; 71: 628633.
  • 28
    Savin VJ, McCarthy ET, Sharma M. Permeability factor in FSGS. Semin Nephrol 2003; 23: 147160.
  • 29
    Haas M, Godfrin Y, Oberbauer R et al. Plasma immunoadsorption treatment in patients with primary focal and segmental glomerulosclerosis. Nephrol Dial Transplant 1998; 13: 20132016.
  • 30
    Andresdottir MB, Ajubi N, Croockewit S, Assmann KJ, Hibrands LB, Wetzels JF. Recurrent focal glomerulosclerosis: Natural course and treatment with plasma exchange. Nephrol Dial Transplant 1999; 14: 26502656.
  • 31
    Mowry JA, McCarthy ET. Cyclosporine in glomerular disease. Sem Nephrol 1996; 16: 548554.
  • 32
    Banfi G, Colturi C, Montagnino G, Ponticelli C. The recurrence of focal segmental glomerulosclerosis in kidney transplant patients treated with cyclosporine. Transplantation 1990; 50: 594596.
  • 33
    Sharma R, Savin VJ. Cyclosporine prevents the increase of glomerular albumin permeability caused by serum from patients with focal segmental glomerulosclerosis. Transplantation 1996; 61: 381383.
  • 34
    Vincenti F, Biava C, Tomlanovitch S et al. Inability of cyclosporine to completely prevent the recurrence of focal glomerulosclerosis after kidney transplantation. Transplantation 1989; 47: 595598.
  • 35
    Kershaw DB, Sedman AB, Kelsch RC, Bunchman TE. Recurrent focal segmental glomerulosclerosis in pediatric renal transplant recipients: Successful treatment with oral cyclophosphamide. Clin Transplant. 1994; 8(6): 546549.