A randomized trial of cyclosporine in patients with steroid-resistant focal segmental glomerulosclerosis

Cattran, Daniel C.; Appel, Gerald B.; Hebert, Lee A.; Hunsicker, Lawrence G.; Pohl, Marc A.; Hoy, W. E.; Maxwell, D. R.; Kunis, Cheryl L.

doi:10.1046/j.1523-1755.1999.00778.x

Cited by 279 publications

(233 citation statements)

References 28 publications

Supporting

Mentioning

201

Contrasting

Unclassified

Order By: Relevance

“…We also found by univariate analysis that BP and ACEi or ARB therapy were associated with our main outcomes, but the impact of either a PR or a CR overwhelmed these in the multivariate analysis (21,22). We used the same definition of PR as in our trial (13) and confirmed that a more clinically meaningful benefit is achieved when the 50% reduction in proteinuria is combined with a nadir Ͻ3.5 g/d. We further found that the nadir proteinuria in the subnephrotic range in the PR group correlated with the rate of renal function decline.…”

Section: Discussionsupporting

confidence: 64%

“…Despite the lack of evidence of its value as a valid surrogate for improved renal survival in FSGS, it is often reported as a positive finding in clinical studies (11)(12)(13)(14).…”

Section: Focal and Segmental Glomerulosclerosis (Fsgs) Is One Of The mentioning

confidence: 99%

“…A CR was defined by a proteinuria value Յ0.3 g/d. A PR was defined by a Ͼ50% reduction in peak proteinuria and to subnephrotic levels (Ͻ3.5 g/d) (13). A relapse was defined by a single proteinuria value Ն3.5 g/d after any remission.…”

Section: Definitionsmentioning

confidence: 99%

See 2 more Smart Citations

Focal and Segmental Glomerulosclerosis

Troyanov

Wall

Miller

et al. 2005

Journal of the American Society of Nephrology

Self Cite

247

211

View full text Add to dashboard Cite

Focal and segmental glomerulosclerosis (FSGS) is one of the most common primary glomerular diseases to terminate in ESRD.A complete remission (CR) confers an excellent long-term prognosis, but the quantitative benefits of partial remissions (PR) have not been defined. This study evaluated the rate of renal function decline (slope of creatinine clearance) and renal survival in nephrotic FSGS patients with CR, PR, or no remission. It also examined relapse rate from remission and its impact on outcome. Multivariate analysis included clinical and laboratory data at presentation and over follow-up, BP control, the agents used, and immunosuppressive therapy. The study cohort was 281 nephrotic FSGS patients who had a minimum of 12 mo of observation and were identified from the Toronto Glomerulonephritis Registry. Over a median follow-up of 65 mo, 55 experienced a CR, 117 had a PR, and 109 had no remission. A PR was independently predictive of slope and survival from renal failure by multivariate analysis (adjusted time-dependent hazard ratio, 0.48; 95% confidence interval, 0.24 to 0.96; P ‫؍‬ 0.04). Immunosuppression with high-dose prednisone was associated with a higher rate of PR and CR. Relapse from PR was frequent (56%) and associated with a more rapid rate of renal function decline and worse renal survival compared with relapse-free partial remitters. Only female gender and the nadir of proteinuria during remission were associated with a sustained remission. A PR in proteinuria and its maintenance are important therapeutic targets in FSGS, with implications for both slowing progression rate and improving renal survival.J (FSGS) is one of the most common causes of primary glomerular disease that terminates in renal failure (1,2). In most series, its 10-yr survival is in the 40 to 60% range (3-7).Severity of proteinuria at onset and during follow-up have been associated with a poor outcome in several series (3-8).Although there is strong evidence that nephrotic patients who experience a complete remission (CR) have a very favorable prognosis (9 -11), the long-term outcome in adults with only a reduction in proteinuria has seldom been reported (11,12). Despite the lack of evidence of its value as a valid surrogate for improved renal survival in FSGS, it is often reported as a positive finding in clinical studies (11)(12)(13)(14).This study addresses the long-term implications of a partial remission (PR) in nephrotic FSGS patients. It compares the rate of renal function decline, relapse, renal failure, and treatment effects among patients with a PR, CR, and no remission (NR). Materials and MethodsAll FSGS patients from the Toronto Glomerulonephritis Registry were considered for this study. This database began in 1974 and includes all biopsy-proven cases of glomerulonephritis from the Toronto area. Patient information at onset is compiled using a standard form, and registrars perform a periodic prospective assessment of the patients' clinical status, medications, and laboratory results (15). We reviewed all previous m...

show abstract

Section: Discussionsupporting

confidence: 64%

“…Despite the lack of evidence of its value as a valid surrogate for improved renal survival in FSGS, it is often reported as a positive finding in clinical studies (11)(12)(13)(14).…”

Section: Focal and Segmental Glomerulosclerosis (Fsgs) Is One Of The mentioning

confidence: 99%

See 1 more Smart Citation

Focal and Segmental Glomerulosclerosis

Troyanov

Wall

Miller

et al. 2005

Journal of the American Society of Nephrology

Self Cite

247

211

View full text Add to dashboard Cite

show abstract

“…Interestingly, functional polymorphisms in the glucocorticoid receptor encoded by NR3C1 have been associated with both relapse and frequent relapse (101). Cyclosporin plus lowdose prednisone was shown in a randomized, controlled trial to be superior to prednisone alone in preserving renal function assessed as creatinine clearance (102). Mycophenolate mofetil has not been tested as monotherapy for FSGS, but it has been tested in combination with glucocorticoids in three trials against active comparators that were either glucocorticoids or cyclosporin (reviewed in Senthil Nayagam et al [103]).…”

Section: Therapeutic Approachesmentioning

confidence: 99%

“…Cyclosporin was shown superior to placebo in the North American collaborative trial of steroid-resistant FSGS, with the primary outcome of CR or PR occurring in 70% with cyclosporin and 4% with placebo (102). Similarly, an open label study of cyclosporin in steroid-resistant nephrotic syndrome in China showed a 75% response rate (137).…”

Section: Therapeutic Approachesmentioning

confidence: 99%

Focal Segmental Glomerulosclerosis

Rosenberg

Kopp

2017

CJASN

434

366

View full text Add to dashboard Cite

Focal segmental glomerulosclerosis (FSGS) is a leading cause of kidney disease worldwide. The presumed etiology of primary FSGS is a plasma factor with responsiveness to immunosuppressive therapy and a risk of recurrence after kidney transplant-important disease characteristics. In contrast, adaptive FSGS is associated with excessive nephron workload due to increased body size, reduced nephron capacity, or single glomerular hyperfiltration associated with certain diseases. Additional etiologies arenow recognized asdrivers of FSGS: high-penetrance geneticFSGSdue to mutations in one of nearly 40 genes, virus-associated FSGS, and medication-associated FSGS. Emerging data support the identification of a sixth category: APOL1 risk allele-associated FSGS in individuals with sub-Saharan ancestry. The classification of a particular patient with FSGS relies on integration of findings from clinical history, laboratory testing, kidney biopsy, and in some patients, genetic testing. The kidney biopsy can be helpful, with clues provided by features on light microscopy (e.g., glomerular size, histologic variant of FSGS, microcystic tubular changes, and tubular hypertrophy), immunofluorescence (e.g., to rule out other primary glomerulopathies), and electron microscopy (e.g., extent of podocyte foot process effacement, podocyte microvillous transformation, and tubuloreticular inclusions). A complete assessment of renal histology is important for establishing the parenchymal setting of segmental glomerulosclerosis, distinguishing FSGS associated with one of many other glomerular diseases from the clinical-pathologic syndrome of FSGS. Genetic testing is beneficial in particular clinical settings. Identifying the etiology of FSGS guides selection of therapy and provides prognostic insight. Much progress has been made in our understanding of FSGS, but important outstanding issues remain, including the identity of the plasma factor believed to be responsible for primary FSGS, the value of routine implementation of genetic testing, and the identification of more effective and less toxic therapeutic interventions for FSGS.

show abstract