Focal segmental glomerulosclerosis (FSGS) has become one the leading causes of kidney disease in the United States. With the incidence of FSGS rising over the past decade, capable treatment options have been a large focus in research. One therapy that shows promise is low density lipoprotein apheresis (LDL-A). This procedure removes lipoproteins containing apolipoprotein-B from the blood, thus reducing the lipid load on the renal system. LDL-A also improves responsiveness to the standard FSGS therapy of corticosteroids and cyclosporine. This paper describes the current LDL-A techniques, offers insight to existing clinical studies employing this therapy, and ultimately highlights LDL-A as a treatment option for FSGS, post-renal transplant, and nephrotic syndrome.

Therapeutic apheresis utilizes apheresis procedures in the treatment of a variety of conditions including kidney disease. Therapeutic plasma exchange (TPE) is the most common modality employed with the rationale of rapid reduction of a pathogenic substance distributed primarily in the intravascular compartment; however other techniques which adsorb such pathogenic substances or alter the immune profile have been utilized in diseases affecting native and transplanted kidneys. This article discusses the modalities and technical details of therapeutic apheresis and summarizes its role in individual diseases affecting the kidney. Complications related to pediatric apheresis procedures and specifically related to apheresis in kidney disease are also discussed. Though therapeutic apheresis modalities are employed frequently in children with kidney disease, most experiences are extrapolated from adult studies. International and national registries need to be established to elucidate the role of apheresis modalities in children with kidney disease.

Recurrent glomerular disease after kidney transplant remains an important cause of allograft failure. Many of the different entities post-transplant still suffer from incomplete knowledge on pathophysiology, and therefore lack targeted and effective therapies. In this review, we focus on specific clinical dilemmas encountered by physicians in managing recurrent glomerular disease by highlighting new insights into the understanding and treatment of post-transplant focal segmental glomerulosclerosis, membranous nephropathy, atypical hemolytic uremic syndrome, C3 glomerulopathy, amyloid light-chain (AL) amyloidosis, and IgA nephropathy.

Focal segmental glomerulosclerosis (FSGS) is one of the most common glomerular diseases leading to renal failure. FSGS has a high risk of recurrence after kidney transplantation. Prevention of recurrent FSGS using rituximab and/or plasmapheresis has been evaluated in multiple small studies with conflicting results.

To assess the risk of recurrence of FSGS after transplantation using prophylactic rituximab with or without plasmapheresis, and plasmapheresis alone compared to the standard treatment group without preventive therapy.

This meta-analysis and systematic review were performed by first conducting a literature search of the MEDLINE, EMBASE, and Cochrane databases, from inception through March 2021; search terms included 'FSGS,' 'steroid-resistant nephrotic syndrome', 'rituximab,' and 'plasmapheresis,'. We identified studies that assessed the risk of post-transplant FSGS after use of rituximab with or without plasmapheresis, or plasmapheresis alone. Inclusion criteria were: Original, published, randomized controlled trials or cohort studies (either prospective or retrospective), case-control, or cross-sectional studies; inclusion of odds ratio, relative risk, and standardized incidence ratio with 95% confidence intervals (CI), or sufficient raw data to calculate these ratios; and subjects without interventions (controls) being used as comparators in cohort and cross-sectional studies. Effect estimates from individual studies were extracted and combined using a random effects model.

Eleven studies, with a total of 399 kidney transplant recipients with FSGS, evaluated the use of rituximab with or without plasmapheresis; thirteen studies, with a total of 571 kidney transplant recipients with FSGS, evaluated plasmapheresis alone. Post-transplant FSGS recurred relatively early. There was no significant difference in recurrence between the group that received rituximab (with or without plasmapheresis) and the standard treatment group, with a pooled risk ratio of 0.82 (95%CI: 0.47-1.45, I 2 = 65%). Similarly, plasmapheresis alone was not associated with any significant difference in FSGS recurrence when compared with no plasmapheresis; the pooled risk ratio was 0.85 (95%CI: 0.60-1.21, I 2 = 23%). Subgroup analyses in the pediatric and adult groups did not yield a significant difference in recurrence risk. We also reviewed and analyzed post-transplant outcomes including timing of recurrence and graft survival.

Overall, the use of rituximab with or without plasmapheresis, or plasmapheresis alone, is not associated with a lower risk of FSGS recurrence after kidney transplantation. Future studies are required to assess the effectiveness of rituximab with or without plasmapheresis among specific patient subgroups with high-risk for FSGS recurrence.

Recurrence of primary focal and segmental glomerulosclerosis following kidney transplantation (rFSGS) is a frequent and severe disease. We studied the time to recurrence of FSGS and its impact on the response to plasma exchange (PE) and graft survival. Between 1990 and 2013, 2730 kidney transplants were performed, including 52 patients with a primary diagnosis of FSGS. Of these patients with primary FSGS, 34 (67%) developed rFSGS. We retrospectively divided these patients into two groups depending on the time to recurrence: early (up to three months after transplantation, n = 26) or late (more than three months after transplantation, n = 8). Survival did not significantly differ between the two groups. In cases of late recurrence, PE was started later and was performed less frequently, and remission was achieved after more PE sessions and longer PE treatment than for the early group (P = 0.01). In early recurrence, resistance to PE at 40 days was associated with no long-term response to PE. PE should be performed as soon as possible after rFSGS. Patients with late rFSGS need to be offered the same treatment regime as those with early rFSGS.

Focal segmental glomerulosclerosis (FSGS) in pediatric patients is typically difficult to treat and will progress to end-stage renal disease (ESRD) in about 10% of cases. Following kidney transplantation, FSGS can recur in up to 56% of renal allografts-with a near 100% recurrence in subsequent transplants.

Four different pediatric centers across the USA and the UK employed a protocol using LDL-apheresis (LDL-A) and pulse solumedrol to treat recurrent FSGS after transplantation in seven patients. All the patients included in this series demonstrated immediate, or early, recurrence of FSGS, which clinically presented as nephrotic-range proteinuria within hours to days after implantation of the kidney.

All patients experienced reductions in urinary protein to creatinine ratios resulting in partial or complete remission. All patients demonstrated improvements in their estimated GFRs at their most recent follow-up since LDL-A discontinuation.

This case series describes the successful treatment, across four different pediatric centers, of seven pediatric patients with recurrent post-transplant FSGS using the Liposorber® LA-15 in combination with pulse solumedrol.

Low-density lipoprotein (LDL) apheresis has been used increasingly in clinical practice for the treatment of renal diseases with nephrotic syndrome (NS), specifically focal segmental glomerulosclerosis (FSGS). Persistent hyperlipidemia for prolonged periods is nephrotoxic and leads to chronic progressive glomerular and tubulointerstitial injury. Effective management of hyperlipidemia with HMG-CoA reductase inhibitors or LDL apheresis in drug-resistant NS patients may prevent the progression of renal disease and, in some patients, resolution of NS symptoms. Available literature reveals beneficial effects of LDL apheresis for NS refractory to drug therapy. Here we update on the current understanding of lipid nephrotoxicity and application of LDL apheresis to prevent progression of renal diseases.

Background: Focal segmental glomerulosclerosis (FSGS) causes end stage renal disease (ESRD) in significant proportion of patients worldwide. Primary FSGS carries poor prognosis and management of FSGS patients, refractory to standard treatments or resistant to steroids, remains a major challenge. Lipoprotein apheresis is a therapeutic approach for drug resistant primary FSGS and post-renal transplant primary FSGS recurrence. Objectives: To examine the safety and probable benefit at 1, 3, 6, 12, and 24-months following completion of apheresis treatment using Liposorber® LA-15 system in patients with nephrotic syndrome (NS), due to refractory primary FSGS or primary FSGS associated NS, in post renal transplant children. Material and Methods: Prospective, multicenter, single-arm intervention study using Liposorber® LA-15 system. Patients ≤21 years old with drug resistant or drug intolerant NS secondary to primary FSGS with glomerular filtration rate (GFR) ≥60 ml/min/1.73 m² or post renal transplant patients ≤21 years old with primary FSGS associated NS were included in the study. Each patient had 12 dextran-sulfate plasma adsorption lipoprotein apheresis sessions over a period of 9 weeks. All patients were followed up at 1, 3, 6, 12, and 24-months following completion of treatment. Results: Of 17 patients enrolled, six were excluded from the outcome analysis (protocol deviations). Of the remaining 11 patients, all but one have completed apheresis treatments. Three patients were lost to follow-up immediately after completion of apheresis and excluded from outcome analysis. At one-month follow-up, 1 of 7 patients (14.3%) attained partial remission of NS while 2 of 4 subjects (50%) and 2 of 3 subjects (66.7%) had partial/complete remission at 3- and 6-months follow-up, respectively. One of two patients followed up for 12 months had complete remission and one patient had partial remission of NS after 24 months. Improved or stable eGFR was noted in all patients over the follow-up period. Conclusion: The results of our multicenter study showed improvement in the response rates to steroid or immunosuppressive therapy and induced complete or partial remission of proteinuria in some of the patients with drug resistant primary FSGS. The main limitation of our study is the small number of subjects and high dropout rate.