Management of focal segmental glomerulosclerosis: Evidence-based recommendations
1999; Elsevier BV; Volume: 55; Linguagem: Inglês
10.1046/j.1523-1755.1999.07004.x
ISSN1523-1755
Autores Tópico(s)Chronic Kidney Disease and Diabetes
ResumoManagement of focal segmental glomerulosclerosis: Evidence-based recommendations. Focal segmental glomerulosclerosis (FSGS) is a diagnosis based on the presence of glomeruli with segmental scarring in association with intracapillary foam cells and adhesions. To develop evidence-based treatment guidelines, a MEDLINE search was conducted, and articles were reviewed using levels of evidence. Graded recommendations were developed according to the level of evidence. There was limited evidence found on which to develop recommendations.Treatment with prednisone of 0.5 to 2 mg/kg/day should be considered in all patients and continued for six months before declaring the patient resistant to therapy. Remission is associated with the use of high doses (more than 60 mg/day) for three months; therefore, if there is a concern about prolonged use, a reduction in dose to 0.5 mg/kg/day should be made only after three months (grade D).The use of cyclosporine A (CsA) at doses to maintain serum levels at 150 to 300 μg/ml may be effective in reducing urinary protein excretion. Relapse after reducing or stopping CsA is very common. Long-term use may be required to maintain remission (grade D).The use of cytotoxic therapy (cyclophosphamide, azathioprine, and chlorambucil) for adults is second-line therapy (grade D).Plasmapheresis or protein adsorption may be recommended for renal transplant patients with recurrent FSGS (grade D). Management of focal segmental glomerulosclerosis: Evidence-based recommendations. Focal segmental glomerulosclerosis (FSGS) is a diagnosis based on the presence of glomeruli with segmental scarring in association with intracapillary foam cells and adhesions. To develop evidence-based treatment guidelines, a MEDLINE search was conducted, and articles were reviewed using levels of evidence. Graded recommendations were developed according to the level of evidence. There was limited evidence found on which to develop recommendations. Treatment with prednisone of 0.5 to 2 mg/kg/day should be considered in all patients and continued for six months before declaring the patient resistant to therapy. Remission is associated with the use of high doses (more than 60 mg/day) for three months; therefore, if there is a concern about prolonged use, a reduction in dose to 0.5 mg/kg/day should be made only after three months (grade D). The use of cyclosporine A (CsA) at doses to maintain serum levels at 150 to 300 μg/ml may be effective in reducing urinary protein excretion. Relapse after reducing or stopping CsA is very common. Long-term use may be required to maintain remission (grade D). The use of cytotoxic therapy (cyclophosphamide, azathioprine, and chlorambucil) for adults is second-line therapy (grade D). Plasmapheresis or protein adsorption may be recommended for renal transplant patients with recurrent FSGS (grade D). In 1957, Rich originally reported focal segmental glomerulosclerosis (FSGS) from a postmortem study of 20 children with nephrotic syndrome1.Rich A.R. A hitherto undescribed vulnerability of the juxta-medullary glomeruli in lipoid nephrosis.Bull Johns Hopkins Hosp. 1957; 100: 173-186PubMed Google Scholar. He described glomerulosclerosis, focal and segmental in location, developing initially in juxtamedullary glomeruli and progressing to involve all glomeruli. Subsequently, there have been detailed descriptions of what may be variants of FSGS or different stages in the evolution of the glomerulopathy. The prevalence of FSGS among patients with glomerulonephritis varies with the indications for renal biopsy at different institutions from 2.5 to 18.7% of patients undergoing renal biopsy for all causes2.D'Agati V. The many masks of focal segmental glomerulosclerosis.Kidney Int. 1994; 46: 1223-1241Abstract Full Text PDF PubMed Scopus (290) Google Scholar,3.Newman W.J. Tisher C.C. McCoy R.C. Gunnells J.C. Krueger R.P. Clapp J.R. Robinson R.R. Focal glomerular sclerosis: Contrasting clinical patterns in children and adults.Medicine (Baltimore). 1976; 55: 67-87Crossref PubMed Scopus (98) Google Scholar or 7 to 12% for those with proteinuria4.Korbet S.M. Schwartz M.M. Lewis E.J. The prognosis of focal segmental glomerular sclerosis of adulthood.Medicine (Baltimore). 1986; 65: 304-311Crossref PubMed Scopus (94) Google Scholar,5.Velosa J.A. Donadio Jr, J.V. Holley K.E. Focal sclerosing glomerulonephropathy: A clinicopathologic study.Mayo Clin Proc. 1975; 50: 121-133PubMed Google Scholar. The etiology is unknown, and for reasons that are unclear, the prevalence of primary FSGS appears to be increasing2.D'Agati V. The many masks of focal segmental glomerulosclerosis.Kidney Int. 1994; 46: 1223-1241Abstract Full Text PDF PubMed Scopus (290) Google Scholar. In adults, FSGS presents with asymptomatic proteinuria in approximately half of the cases and with features of the nephrotic syndrome in half. Hypertension and a reduction in renal function are also commonly seen. In approximately one third of the cases, microscopic hematuria is present, even in the absence of urinary or respiratory tract infection3.Newman W.J. Tisher C.C. McCoy R.C. Gunnells J.C. Krueger R.P. Clapp J.R. Robinson R.R. Focal glomerular sclerosis: Contrasting clinical patterns in children and adults.Medicine (Baltimore). 1976; 55: 67-87Crossref PubMed Scopus (98) Google Scholar,4.Korbet S.M. Schwartz M.M. Lewis E.J. The prognosis of focal segmental glomerular sclerosis of adulthood.Medicine (Baltimore). 1986; 65: 304-311Crossref PubMed Scopus (94) Google Scholar. The clinical course of this condition varies. In patients who have had a treatment-induced complete remission, the course of disease appears to be stable. In patients who have been treated but have not had a remission, there is deterioration of renal function, with a large portion of patients (30 to 63%) developing renal failure6.Nagai R. Cattran D.C. Pei Y. Steroid therapy and prognosis of focal segmental glomerulosclerosis in the elderly.Clin Nephrol. 1994; 42: 18-21PubMed Google Scholar, 7.Beaufils H. Alphonse J.C. Guedon J. Legrain M. Focal glomerulosclerosis: natural history and treatment: A report of 70 cases.Nephron. 1978; 21: 75-85Crossref PubMed Google Scholar, 8.Pei Y. Cattran D. Delmore T. Katz A. Lang A. Rance P. Evidence suggesting under-treatment in adults with idiopathic focal segmental glomerulosclerosis: Regional glomerulonephritis registry.Am J Med. 1987; 82: 938-944Abstract Full Text PDF PubMed Scopus (141) Google Scholar, 9.Banfi G. Moriggi M. Sabadini E. Fellin G. D'Amico G. Ponticelli C. The impact of prolonged immunosuppression on the outcome of idiopathic focal-segmental glomerulosclerosis with nephrotic syndrome in adults: A collaborative retrospective study.Clin Nephrol. 1991; 36: 53-59PubMed Google Scholar, 10.Korbet S.M. Schwartz M.M. Lewis E.J. Primary focal segmental glomerulosclerosis: Clinical course and response to therapy.Am J Kidney Dis. 1994; 23: 773-783Abstract Full Text PDF PubMed Scopus (235) Google Scholar, 11.Rydel J.J. Korbet S.M. Borok R.Z. Schwartz M.M. Focal segmental glomerular sclerosis in adults: Presentation, course, and response to therapy.Am J Kidney Dis. 1995; 25: 534-542Abstract Full Text PDF PubMed Scopus (242) Google Scholar. Untreated nephrotic patients have been described as having an outcome similar to those who failed a trial of therapy. Untreated non-nephrotic patients may have a better outcome than the untreated nephrotic patients, but reports are mixed in this patient population. However, follow-up in retrospective studies usually extends to only two to five years, and this may not be adequate in such a heterogenous condition. Negative prognostic indicators are similar to those in other glomerular diseases: an increased serum creatinine level at diagnosis and interstitial scarring on renal biopsy11.Rydel J.J. Korbet S.M. Borok R.Z. Schwartz M.M. Focal segmental glomerular sclerosis in adults: Presentation, course, and response to therapy.Am J Kidney Dis. 1995; 25: 534-542Abstract Full Text PDF PubMed Scopus (242) Google Scholar. Two other indicators—nephrotic range proteinuria and hypertension—are not cited consistently7.Beaufils H. Alphonse J.C. Guedon J. Legrain M. Focal glomerulosclerosis: natural history and treatment: A report of 70 cases.Nephron. 1978; 21: 75-85Crossref PubMed Google Scholar, 8.Pei Y. Cattran D. Delmore T. Katz A. Lang A. Rance P. Evidence suggesting under-treatment in adults with idiopathic focal segmental glomerulosclerosis: Regional glomerulonephritis registry.Am J Med. 1987; 82: 938-944Abstract Full Text PDF PubMed Scopus (141) Google Scholar, 9.Banfi G. Moriggi M. Sabadini E. Fellin G. D'Amico G. Ponticelli C. The impact of prolonged immunosuppression on the outcome of idiopathic focal-segmental glomerulosclerosis with nephrotic syndrome in adults: A collaborative retrospective study.Clin Nephrol. 1991; 36: 53-59PubMed Google Scholar, 11.Rydel J.J. Korbet S.M. Borok R.Z. Schwartz M.M. Focal segmental glomerular sclerosis in adults: Presentation, course, and response to therapy.Am J Kidney Dis. 1995; 25: 534-542Abstract Full Text PDF PubMed Scopus (242) Google Scholar, 12.Miyata J. Takebayashi S. Taguchi T. Naito S. Harada T. Evaluation and correlation of clinical and histological features of focal segmental glomerulosclerosis.Nephron. 1986; 44: 115-120Crossref PubMed Google Scholar. These indicators do not forecast which patients will respond to therapy but do predict long-term outcome11.Rydel J.J. Korbet S.M. Borok R.Z. Schwartz M.M. Focal segmental glomerular sclerosis in adults: Presentation, course, and response to therapy.Am J Kidney Dis. 1995; 25: 534-542Abstract Full Text PDF PubMed Scopus (242) Google Scholar. Some patients have a malignant clinical course with rapid deterioration in renal function and are unresponsive to therapy12.Miyata J. Takebayashi S. Taguchi T. Naito S. Harada T. Evaluation and correlation of clinical and histological features of focal segmental glomerulosclerosis.Nephron. 1986; 44: 115-120Crossref PubMed Google Scholar. Recurrence in renal allografts in this population is common (15 to 55%)12.Miyata J. Takebayashi S. Taguchi T. Naito S. Harada T. Evaluation and correlation of clinical and histological features of focal segmental glomerulosclerosis.Nephron. 1986; 44: 115-120Crossref PubMed Google Scholar, 13.Brown C.B. Cameron J.S. Turner D.R. Chantler C. Ogg C.S. Williams D.G. Bewick M. Focal segmental glomerulosclerosis with rapid decline in renal function ("malignant FSGS").Clin Nephrol. 1978; 10: 51-61PubMed Google Scholar, 14.Artero M. Biava C. Amend W. Tomlanovich S. Vincenti F. Recurrent focal glomerulosclerosis: Natural history and response to therapy.Am J Med. 1992; 92: 375-383Abstract Full Text PDF PubMed Scopus (242) Google Scholar. Terms used in renal pathology must be clear to ensure appropriate referencing. The term focal means that only some glomeruli in the biopsy are involved, whereas segmental refers to involvement of only some lobules of any given glomerulus. Global sclerosis refers to the total involvement of one entire glomerulus. Variants of the disease exist: diffuse mesangial hypercellularity, tip lesion (the segmental lesion is adjacent to the epithelial cells of the early proximal tubule and to the tubular pole of Bowman's capsule), capillary collapse, and focal glomerular obsolescence. Biopsy findings similar to idiopathic FSGS are found secondary to known etiologic agents such as human immunodeficiency virus (HIV) or heroin. These and other forms of secondary FSGS must be ruled out when patients are to be included in studies or clinically treated2.D'Agati V. The many masks of focal segmental glomerulosclerosis.Kidney Int. 1994; 46: 1223-1241Abstract Full Text PDF PubMed Scopus (290) Google Scholar. The definitions for complete and partial remission often differ between authors. A complete remission may mean reduction of urinary protein excretion to zero, less than 250 mg, or less than 300 mg/day, whereas partial remission may refer to a reduction of daily proteinuria to 0.3 to 2.0 g/day, or a reduction to below nephrotic-range proteinuria. Similarly, definitions of renal insufficiency differ, for example, a serum creatinine of more than 1.5 mg/dl, a creatinine clearance of less than 0.8 ml/seconds, or a doubling of serum creatinine. Regardless of the variance of these definitions for these terms across articles, the outcomes appear to be consistent. Evidence was initially compiled with a MEDLINE literature search using a primary search technique for review and clinical research articles. Secondary searches were done using the reference lists of review articles retrieved initially, and searches of personal files were also done. Published articles were categorized according to design methodology and were reviewed and graded for level of evidence using guidelines published previously by the Canadian Hypertension Society15.Carruthers S.G. Larochelle P. Haynes R.B. Petrasovits A. Schiffrin E.L. Report of the Canadian Hypertension Society Consensus Conference. I. Introduction.Can Med Assoc J. 1993; 149: 289-292PubMed Google Scholar; graded recommendations were developed based on the evidence (Table 1).Table 1Levels of evidenceLevel 1:RCT with hard end-pointLevel 2:RCT with surrogate end-pointLevel 3:Non-R trial with a control group, or subgroup analysis of an RCTLevel 4:Before and after studyLevel 5:Case series> 10 patientsLevel 6:Case series <10 patientsRecommendations Grade A:Based upon Level 1 evidence Grade B:Based upon Level 2 evidence Grade C:Based upon Level 3 evidence Grade D:Based upon Level 4 or lower evidence or expert opinionAbbreviations are: RCT, randomized clinical trial; R, randomized. Open table in a new tab Abbreviations are: RCT, randomized clinical trial; R, randomized. Articles describing the clinical course or reporting clinical trials of patients with FSGS often included patients with steroid-resistant, steroid-dependent, or frequently relapsing nephrotic syndrome, without a definitive renal biopsy diagnosis. The studies reviewed in this article are predominantly those including adults with a biopsy-proven diagnosis. Because many reports include other patients (children or patients treated without renal biopsy), the sample size noted in the tables may be smaller than the total reported in the articles. Limiting the review to adult FSGS patients often leaves an inadequate sample size for definitive evidence and lowers the level of evidence15.Carruthers S.G. Larochelle P. Haynes R.B. Petrasovits A. Schiffrin E.L. Report of the Canadian Hypertension Society Consensus Conference. I. Introduction.Can Med Assoc J. 1993; 149: 289-292PubMed Google Scholar. Treatment with prednisone of 0.5 to 2.0 mg/kg/day should be considered for patients with FSGS. Treatment should continue for a total duration of six months before declaring the patient steroid resistant. Remission is associated with a dose of at least 60 mg/day. If necessary, the dose may be reduced to 0.5 mg/kg/day, but only after three months (grade D). An overview of the evidence reveals several key findings about prednisone therapy. The dose of prednisone needs to be approximately 60 mg/day initially. The duration of therapy needs to be approximately six months before concluding that the patient is resistant to prednisone therapy; no clinical or biopsy finding predicts the response to therapy. Adults respond as well as children to therapy. Complete remission predicts a good long-term outcome, and nontreatment or lack of response to treatment predicts poor outcome with the development of chronic renal failure (CRF). A summary of the relevant studies is presented in Table 26.Nagai R. Cattran D.C. Pei Y. Steroid therapy and prognosis of focal segmental glomerulosclerosis in the elderly.Clin Nephrol. 1994; 42: 18-21PubMed Google Scholar, 7.Beaufils H. Alphonse J.C. Guedon J. Legrain M. Focal glomerulosclerosis: natural history and treatment: A report of 70 cases.Nephron. 1978; 21: 75-85Crossref PubMed Google Scholar, 8.Pei Y. Cattran D. Delmore T. Katz A. Lang A. Rance P. Evidence suggesting under-treatment in adults with idiopathic focal segmental glomerulosclerosis: Regional glomerulonephritis registry.Am J Med. 1987; 82: 938-944Abstract Full Text PDF PubMed Scopus (141) Google Scholar, 9.Banfi G. Moriggi M. Sabadini E. Fellin G. D'Amico G. Ponticelli C. The impact of prolonged immunosuppression on the outcome of idiopathic focal-segmental glomerulosclerosis with nephrotic syndrome in adults: A collaborative retrospective study.Clin Nephrol. 1991; 36: 53-59PubMed Google Scholar, 11.Rydel J.J. Korbet S.M. Borok R.Z. Schwartz M.M. Focal segmental glomerular sclerosis in adults: Presentation, course, and response to therapy.Am J Kidney Dis. 1995; 25: 534-542Abstract Full Text PDF PubMed Scopus (242) Google Scholar, 12.Miyata J. Takebayashi S. Taguchi T. Naito S. Harada T. Evaluation and correlation of clinical and histological features of focal segmental glomerulosclerosis.Nephron. 1986; 44: 115-120Crossref PubMed Google Scholar, 16.Saint-Hillier Y. Morel-Maroger L. Woodrow D. Richet G. Focal and segmental hyalinosis.Adv Nephrol. 1975; 5: 67-88PubMed Google Scholar, 17.Jenis E.H. Teichman S. Briggs W.A. Sandler P. Hollerman C.E. Calcagno P.L. Knieser M.R. Jensen G.E. Valeski J.E. Focal segmental glomerulosclerosis.Am J Med. 1974; 57: 695-705Abstract Full Text PDF PubMed Scopus (58) Google Scholar, 18.Lim V.S. Sibley R. Spargo B. Adult lipoid nephrosis: Clinicopathological correlations.Ann Intern Med. 1974; 81: 314-320Crossref PubMed Scopus (47) Google Scholar. There have been no randomized clinical trials of steroid therapy; most reports are case series, with or without controls, and are thus categorized as level 4 or 5 evidence. Most early reports provided few details, if any, on the dose or duration of therapy. Response rates varied tremendously. Lim, Sibley and Spargo reported no responders from 10 FSGS patients receiving prednisone for a median of three weeks18.Lim V.S. Sibley R. Spargo B. Adult lipoid nephrosis: Clinicopathological correlations.Ann Intern Med. 1974; 81: 314-320Crossref PubMed Scopus (47) Google Scholar. However, Korbet, Schwartz and Lewis reported a 50% response rate (of 16 patients with nephrotic syndrome) and noted that some responses occurred by an average of 3.75 months (range 1 to 10 months), and complete remission occurred at 5.75 to 6.75 months in the three patients who had complete remission4.Korbet S.M. Schwartz M.M. Lewis E.J. The prognosis of focal segmental glomerular sclerosis of adulthood.Medicine (Baltimore). 1986; 65: 304-311Crossref PubMed Scopus (94) Google Scholar. Treatment included 60 mg/day of prednisone for a minimum of one month. In comparing patients who had a remission with those who were not treated or had no response, there was a significant difference in the change in renal function over time that favored the treatment-response group.Table 2Corticosteroid therapy reportsLevel of evidenceAuthor [Ref]# AdultsTreatment# Responders/# treated remission rate %Rate of CRFLevel 4St Hillier16.Saint-Hillier Y. Morel-Maroger L. Woodrow D. Richet G. Focal and segmental hyalinosis.Adv Nephrol. 1975; 5: 67-88PubMed Google ScholarTotal 85, NS 30 Non-NS 5517/30 NS treated Prednisone16/17 (94%)Beaufils7.Beaufils H. Alphonse J.C. Guedon J. Legrain M. Focal glomerulosclerosis: natural history and treatment: A report of 70 cases.Nephron. 1978; 21: 75-85Crossref PubMed Google ScholarTotal 70, NS 35 Non-NS 3526/35 NS treated Prednisone6/20 (23%)NS 55%Non-NS 9%Pei8.Pei Y. Cattran D. Delmore T. Katz A. Lang A. Rance P. Evidence suggesting under-treatment in adults with idiopathic focal segmental glomerulosclerosis: Regional glomerulonephritis registry.Am J Med. 1987; 82: 938-944Abstract Full Text PDF PubMed Scopus (141) Google ScholarTotal N = 55 NS 30 Non-NS 25Prednisone7/18 (39%)No remission 45%Remission 4%Rydel11.Rydel J.J. Korbet S.M. Borok R.Z. Schwartz M.M. Focal segmental glomerular sclerosis in adults: Presentation, course, and response to therapy.Am J Kidney Dis. 1995; 25: 534-542Abstract Full Text PDF PubMed Scopus (242) Google Scholar81, NS 60 Non-NS 2136/60 treated15/30 (50%)If remission 0% No remission 59% Untreated NS 30%PrednisoneMiyata12.Miyata J. Takebayashi S. Taguchi T. Naito S. Harada T. Evaluation and correlation of clinical and histological features of focal segmental glomerulosclerosis.Nephron. 1986; 44: 115-120Crossref PubMed Google Scholar32 NSPrednisone18/32 (56%)Mesangial hypercellularity associated with poor prognosisNagai6.Nagai R. Cattran D.C. Pei Y. Steroid therapy and prognosis of focal segmental glomerulosclerosis in the elderly.Clin Nephrol. 1994; 42: 18-21PubMed Google ScholarTotal N = 17 NS 128/12 NS treated Prednisone4/9 (44%)No treatment or no remission 63%Level 5Banfi9.Banfi G. Moriggi M. Sabadini E. Fellin G. D'Amico G. Ponticelli C. The impact of prolonged immunosuppression on the outcome of idiopathic focal-segmental glomerulosclerosis with nephrotic syndrome in adults: A collaborative retrospective study.Clin Nephrol. 1991; 36: 53-59PubMed Google Scholar59 (all NS)Prednisone N = 27 Prednisone ± Cytotoxic N = 3220/27 (74%)16/32 (50%)Korbet4.Korbet S.M. Schwartz M.M. Lewis E.J. The prognosis of focal segmental glomerular sclerosis of adulthood.Medicine (Baltimore). 1986; 65: 304-311Crossref PubMed Scopus (94) Google ScholarTotal = 46, NS 29 Non-NS 1716/29 NS treated Prednisone8/16 (50%)Jenis17.Jenis E.H. Teichman S. Briggs W.A. Sandler P. Hollerman C.E. Calcagno P.L. Knieser M.R. Jensen G.E. Valeski J.E. Focal segmental glomerulosclerosis.Am J Med. 1974; 57: 695-705Abstract Full Text PDF PubMed Scopus (58) Google ScholarTotal = 11 NS 9Prednisone ± Azathioprine2/6 (33%)Velosa5.Velosa J.A. Donadio Jr, J.V. Holley K.E. Focal sclerosing glomerulonephropathy: A clinicopathologic study.Mayo Clin Proc. 1975; 50: 121-133PubMed Google Scholar32Prednisone11/26 (42%)Newman3.Newman W.J. Tisher C.C. McCoy R.C. Gunnells J.C. Krueger R.P. Clapp J.R. Robinson R.R. Focal glomerular sclerosis: Contrasting clinical patterns in children and adults.Medicine (Baltimore). 1976; 55: 67-87Crossref PubMed Scopus (98) Google ScholarTotal = 17, NS 7Prednisone3/6 (50%)Lim18.Lim V.S. Sibley R. Spargo B. Adult lipoid nephrosis: Clinicopathological correlations.Ann Intern Med. 1974; 81: 314-320Crossref PubMed Scopus (47) Google Scholar10Prednisone0/10 (0%) Open table in a new tab In several studies, response rates varied between 2 to 94%, but details on the dose of prednisone and duration of treatment were not included3.Newman W.J. Tisher C.C. McCoy R.C. Gunnells J.C. Krueger R.P. Clapp J.R. Robinson R.R. Focal glomerular sclerosis: Contrasting clinical patterns in children and adults.Medicine (Baltimore). 1976; 55: 67-87Crossref PubMed Scopus (98) Google Scholar, 5.Velosa J.A. Donadio Jr, J.V. Holley K.E. Focal sclerosing glomerulonephropathy: A clinicopathologic study.Mayo Clin Proc. 1975; 50: 121-133PubMed Google Scholar, 7.Beaufils H. Alphonse J.C. Guedon J. Legrain M. Focal glomerulosclerosis: natural history and treatment: A report of 70 cases.Nephron. 1978; 21: 75-85Crossref PubMed Google Scholar, 12.Miyata J. Takebayashi S. Taguchi T. Naito S. Harada T. Evaluation and correlation of clinical and histological features of focal segmental glomerulosclerosis.Nephron. 1986; 44: 115-120Crossref PubMed Google Scholar, 16.Saint-Hillier Y. Morel-Maroger L. Woodrow D. Richet G. Focal and segmental hyalinosis.Adv Nephrol. 1975; 5: 67-88PubMed Google Scholar, 17.Jenis E.H. Teichman S. Briggs W.A. Sandler P. Hollerman C.E. Calcagno P.L. Knieser M.R. Jensen G.E. Valeski J.E. Focal segmental glomerulosclerosis.Am J Med. 1974; 57: 695-705Abstract Full Text PDF PubMed Scopus (58) Google Scholar. The importance of dose and duration of therapy and the possibility of physician bias in the undertreatment of adults with FSGS compared with children was put forth by Pei et al in 1987 in a report that included 55 adult patients8.Pei Y. Cattran D. Delmore T. Katz A. Lang A. Rance P. Evidence suggesting under-treatment in adults with idiopathic focal segmental glomerulosclerosis: Regional glomerulonephritis registry.Am J Med. 1987; 82: 938-944Abstract Full Text PDF PubMed Scopus (141) Google Scholar. Treatment with prednisone (with or without cytotoxic drugs) was given to 18 adult patients. The median duration of treatment was six months. Prednisone dosages varied greatly, from 0.3 to 2 mg/kg/day. Seven adults had complete remissions. The average follow-up was five years, and 96% of the patients who had a complete remission had preservation of renal function, whereas the probability of CRF was 45% in those who had not responded or who were not treated. This level 4 study showed that the probability of remission with a long duration of therapy was as likely in adults (39%) as it was in children (44%) with FSGS and that age was not a factor in treatment response or long-term outcome. Physician bias was likely the reason for only 33% of adults being given a trial of therapy compared with 90% of children. The same group of investigators reported that the incidence of FSGS was much lower in older patients (more than 60 years) undergoing renal biopsy (17 of 822 biopsies or 2%) even though the prevalence of nephrotic syndrome in patients coming for renal biopsy was similar to younger patients6.Nagai R. Cattran D.C. Pei Y. Steroid therapy and prognosis of focal segmental glomerulosclerosis in the elderly.Clin Nephrol. 1994; 42: 18-21PubMed Google Scholar. Of the 17 older patients, 9 had received treatment. Four (44%) achieved complete remission; there were no relapses in those patients who achieved remission (mean follow-up was 37 months), and none of them progressed to renal failure. No untreated patients had a remission, and 9 of the 14 untreated or nonresponders-to-treatment did progress. The treatment that these patients had received was prednisone, alone or combined with cytotoxic therapy, and the maximum dose was 100 mg prednisone alternate days. The mean time to remission was four months. This level 4 study is consistent with the study results from younger patients in the Toronto Glomerulonephritis Registry reported by Pei et al8.Pei Y. Cattran D. Delmore T. Katz A. Lang A. Rance P. Evidence suggesting under-treatment in adults with idiopathic focal segmental glomerulosclerosis: Regional glomerulonephritis registry.Am J Med. 1987; 82: 938-944Abstract Full Text PDF PubMed Scopus (141) Google Scholar. In 1995, Rydel et al reported a retrospective assessment of 81 patients, including 60 with nephrotic syndrome11.Rydel J.J. Korbet S.M. Borok R.Z. Schwartz M.M. Focal segmental glomerular sclerosis in adults: Presentation, course, and response to therapy.Am J Kidney Dis. 1995; 25: 534-542Abstract Full Text PDF PubMed Scopus (242) Google Scholar. Thirty patients had received treatment, and 15 responded (10 had complete and 5 had partial remissions). Treatment consisted of more than 60 mg/day for a minimum of two months, followed by a tapering schedule. Remission was more common in patients who received a dose of 60 mg/day or more of prednisone for a longer period of time (2.7 vs. 1.5 months for responders and nonresponders, respectively). Remission was not prompt, but most patients did respond by four months of treatment. Prognostic factors associated with the development of CRF were the degree of interstitial fibrosis on renal biopsy and an elevated serum creatinine level at the time of biopsy. These prognostic factors did not predict response to therapy. This level 4 study reinforced that treatment of FSGS with a high dose of prednisone could effect a complete or partial remission in adult patients, but the treatment must be continued for four to six months; attaining remission with treatment was associated with a better long-term prognosis. A series of 14 patients with collapsing FSGS was reported by Detwiler et al19.Detwiler R.K. Falk R.J. Hogan S.L. Jennette J.C. Collapsing glomerulopathy: A clinically and pathologically distinct variant of segmental glomerulosclerosis.Kidney Int. 1994; 45: 1416-1424Abstract Full Text PDF PubMed Scopus (267) Google Scholar. Only four received treatment with corticosteroids (one of these four also received cytotoxic therapy), and only one had a complete remission (level 6 evidence). A recent study of 43 patients (both children and adults) with collapsing FSGS found that none of the 26 patients treated with prednisone alone benefited. When compared with age-matched controls with classic FSGS, the collapsing variant was more rapidly progressive, with a time course of only 13.0 months to end-stage renal failure compared with 62.5 months (level 5 evidence)20.Valeri A. Barisoni L. Appel G.B. Seigle R. D'Agati V. Idiopathic collapsing focal segmental glomerulosclerosis: A clinicopathologic study.Kidney Int. 1996; 50: 1734-1746Abstract Full Text PDF PubMed Scopus (237) Google Scholar. In summary, prednisone treatment at approximately 1 mg/kg or 60 mg/day can induce a remission but must be given for six months before concluding that the patient is steroid resistant. The use of cyclosporine A (CsA) at doses of approximately 5 mg/kg/day may be effective in reducing urinary protein excretion. Relapse after reducing the dose or stopping CsA is very common (grade B). Long-term use of CsA may be required to maintain remission (grade D). Prospective studies have not been conducted to compare corticosteroid therapy with placebo therapy. However, the prospective studies shown in Table 3 were designed to recruit patients who had failed a trial of corticosteroid therapy and to assess the addition or substitution of either a cytotoxic agent or cyclosporine21.Ponticelli C. Rizzoni G. Edefonti A. Altieri P. Rivolta E. Rinaldi S. Ghio L. Lu
Referência(s)