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Saudi Journal of Kidney Diseases and Transplantation
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ORIGINAL ARTICLE Table of Contents   
Year : 1994  |  Volume : 5  |  Issue : 3  |  Page : 354-358
Ten years follow-up of idiopathic focal and segmental glomerulosclerosis


1 Division of Nephrology, King Fahd Specialist Hospital, Buraidah, Al-Gassim, Saudi Arabia
2 Department of Nephrology, Institute of Medical Sciences, Banaras Hindu University, Varanasi, India
3 Department of Immunopathology, Institute of Medical Sciences, Banaras Hindu University, Varanasi, India
4 Department of Medicine, University of Kuwait, Kuwait

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   Abstract 

Sixty-four biopsy proven cases of idiopathic focal and segmental glomerulosclerosis (FSGS) were studied retrospectively for 10 years. The mean age of the study patients was 29.5 years and 81.2% of the patients were males. Edema, hematuria, hypertension and azotemia were the main presenting features. All cases were initially treated with steroids alone. Nineteen cases (29.7%) had complete and 14 patients (21.9%) had partial remission while 31 cases (48.4%) had no response. Twenty non-responsive cases were given cyclophosphamide in addition to steroids and seven (35%) patients had complete remission and a similar number had partial remission. Patients who had azotemia, hypertension, nephrotic range proteinuria and diffuse mesangial hypercellularity in addition to segmental sclerosis on renal histology at presentation were classified as malignant FSGS. There were eight such cases of which two showed partial response to steroids. One patient went into complete remission with steroids and cyclophosphamide while two others showed partial remission. Mean duration before the occurrence of renal death in benign FSGS patients was six years while all malignant FSGS cases had renal death within two years. Differentiating benign and malignant FSGS will help in prognostication of patients with this pathology.

Keywords: FSGS, Nephrotic Syndrome, Steroids, Glomerulonephritis, Cyclophosphamide

How to cite this article:
Singh R G, Agarwal D K, Usha, Johny K V, Jaiprakash. Ten years follow-up of idiopathic focal and segmental glomerulosclerosis. Saudi J Kidney Dis Transpl 1994;5:354-8

How to cite this URL:
Singh R G, Agarwal D K, Usha, Johny K V, Jaiprakash. Ten years follow-up of idiopathic focal and segmental glomerulosclerosis. Saudi J Kidney Dis Transpl [serial online] 1994 [cited 2020 Apr 10];5:354-8. Available from: http://www.sjkdt.org/text.asp?1994/5/3/354/41166

   Introduction Top


Focal and segmental glomerulosclerosis (FSGS) is a recognized entity responsible for nephrotic and nephritic syndromes as well as asymptomatic proteinuria and/or hematuria. Since its first recognition by Arnold Rich [1] in 1957 and subsequent naming as FSGS by various authors [2],[3] many controversies still exist regarding its spectrum, course, modality of treatment and its response as well as longterm prognosis [4],[5],[6],[7],[8] . Numerous reports are available on these aspects but a definite line of management has not been charted out clearly. The present study was planned to record the spectrum of FSGS as well as the long-term effects of its treatment.


   Materials and Methods Top


Sixty-four biopsy proven cases of idiopathic FSGS seen during the 10 years period from 1981 to 1991 were studied and the follow-up data were analyzed in the Department of Nephrology, Faculty of Medicine, Institute of Medical Sciences, Banaras Hindu University, Varanasi, India. Clinical features and laboratory tests including 24 hours urinary protein excretion, blood urea, serum levels of total protein, albumin, globulin and creatinine were recorded. Response to treatment and subsequent course were documented in all study patients. Hypertension was defined as diastolic pressure above 95 mm Hg and systolic pressure above 150 mm Hg on at least three consecutive occasions. Patients having 24 hour urinary protein excretion of 3.5 gm/1.73 m2 /day or more were considered as having nephrotic range proteinuria, while proteinuria between 200 mg and 3.5 gm/day was considered as non-nephrotic range proteinuria.

To start with, all cases were treated with steroids alone in the dose of 2 mg/kg body weight of prednisolone given orally as a single dose on alternate days for eight weeks. Complete remission was defined when proteinuria became < 200 mg/day whereas partial remission was labeled when proteinuria was between 200 mg to 2 gm/day. The cases who were steroid non-responsive or steroid responsive cases with subsequent multiple relapses (3 or more), were treated with cyclophosphamide in the dose of 2 mg/ kg/day for 8 to 12 weeks administered in a single dose orally, in addition to teroids. The patients having azotemia, nephrotic range proteinuria, gross hematuria, diffuse mesangial hypercellularity with tubular atrophy on renal histology, poor response to treatment and rapid deterioration of renal functions were labeled as having malignant FSGS, as suggested by Brown, et al [9] . Renal death was defined as need for treatment with dialysis or transplantation or death from renal insufficiency. Actuarial survival curve from onset of the disease was calculated according to the method used by Anderson et al [10] .


   Results Top


Out of 64 cases studied, males predominated (81.2%) and maximum number of cases were in the 16 to 30 year age group with a mean age of 29.5 years [Table 1].

Edema was present in all cases, while hypertension was noted in 27 (42.2%). Hematuria was found in 22 cases (34.4%) of whom eight (36.4%) had gross hematuria and 14 (63.6%) had microscopic hematuria. Azotemia at the time of presentation was found in 24 cases (37.5%).

Twenty-four hour urinary protein excretion was found to be in the range of 1.2 to 12 gm (mean 5.53 2.89 gm). Forty-six patients (71.9%) had nephrotic range proteinuria and in 18 (28.1%) the proteinuria was in the nonnephrotic range. Massive proteinuria (more than 10 gm/24 hrs) was found in 9 cases (14.1%). All cases of malignant FSGS had nephrotic range proteinuria (mean 7.81 .91 gm/24 hrs) in contrast to patients with benign FSGS in whom nephrotic range proteinuria was found in 38 patients (67.8%) (Mean 5.21 2.9 gm/24 hrs).

Mean serum total protein values were in the range of 22 to 69 gm/1 (mean 45.4 10.9 gm/1) with a mean serum albumin of 19.6 gm/1 and mean serum globulin of 25.9 5.2 gm/1.

Renal biopsy was performed in all cases. All patients showed typical findings of FSGS while eight cases in addition showed marked mesangial cell proliferation with IgG and C3 deposits on immunoflourescence associated with patchy tubular atrophy and mononuclear cell infiltration in the interstitium (malignant FSGS) [Figure 1].

All cases were initially treated with steroids alone. Nineteen (29.7%) showed complete remission and 14 (21.9%) showed partial remission while no response was found in the remaining 31 patients (48.4%). Of the patients who did not respond to steroids, eight were lost to follow-up, three other patients refused further treatment with cytotoxic drugs and the remaining twenty patients were given steroids and cyclophosphamide. Complete and partial remission was noted in seven cases (35%) each. No response was found in six patients (30%).

Eight (12.5%) patients had features suggestive of malignant FSGS. With steroid treatment, two (25%) of these cases showed partial remission. No response was noted in the remaining six cases (75%) who then received steroids and cyclophosphamide. Complete remission was noted in one case (16.7%) and partial remission, in two (33.3%), and the remaining three patients (50%) showed no response.

Among the 56 patients with benign FSGS 19 (33.9%) showed complete remission and 12 (21.4%) showed partial remission with steroids alone while 25 cases showed no response (44.7%). Fourteen cases were given steroids along with cytotoxic drugs. Complete remission and partial remission were found in six (42.9%) and five (35.7%) cases respectively. Three cases (21.4%) showed no response. [Table 2] summarizes the treatment and response in the study patients.

Renal death occurred in 12 of the 56 cases. Mean duration of renal death in patients with benign FSGS was six years (range 3 to 9 years) while it was 13.4 months (range 4 to 24 months) in patients with malignant FSGS. The actuarial renal survival rate of FSGS was 68.6% at 5 years and 27.3% at 10 years. In the benign FSGS group actuarial renal survival rate was 80% at 5 years and 33.3% at 10 years while all malignant FSGS cases had renal death within 24 months [Figure 2].


   Discussion Top


Focal and segmental glomerulosclerosis was diagnosed on clinical and histological criteria used by previous workers and typical segmental lesion with hyaline deposit and fusion of at least two capillary loops were required for the diagnosis [11],[12] . Cases with secondary FSGS were excluded based on clinical and laboratory criteria. Our finding of male predominance is similar to that noted by other workers [5],[13] .

Most of the study cases had nephrotic range proteinuria. The degree of proteinuria was more in malignant FSGS in comparison to benign FSGS, a finding similar to that observed by Beaufils et al [13] . Serum albumin levels were markedly diminished in these cases. On histopathology, the hallmark of patients with malignant FSGS was the presence of mesangial proliferation. It is difficult to say whether these cases were basically mesangial proliferative glomerulonephritis having FSGS superimposed or FSGS cases having mesangial proliferation.

Steroids were tried in all cases and it was noted that nearly half of the cases were steroid resistant, while others showed either complete or partial remission. Similar results have been noticed by various other workers also [4],[5] . But the response was poor in cases with malignant FSGS.

In contrast to other studies [6],[7],[14] , 70% of our cases who were initially steroid resistant, responded to combination therapy. Similar results have been shown by Griswold et al [8] who showed good response to cytotoxic drugs administered along with intravenous steroids.

Fifty-six patients were available for followup. The actuarial renal survival rates of these cases were 68.6% and 27.3% at five and 10 years respectively. Cameron et al, found five and 10 year survival rates at 70% and 40% respectively [4] . The actuarial renal survival rate was better in the benign FSGS group while all cases with malignant FSGS had renal death within 24 months (mean 13.4 months).

We concur with the earlier suggestion [9] that FSGS exists in two varieties, benign and malignant and certain features favor the malignant variety. They are:

a) Presence of hypertension, gross hematuria and azotemia at presentation.

b) Presence of heavy proteinuria (usually more than 7 gm/24 hours).

c) Occurrence of mesangial proliferation on histopathology along with other features of FSGS.

d) Poor response to therapy and a very rapidly deteriorating course.

Identification of malignant FSGS is important since it will facilitate proper assessment of the prognosis as well as further line of management. Also, early recurrence of the disease with unfavorable consequences has been reported in such patients following renal transplantation [9] .

In summary, FSGS is a male dominant disease with hypertension and hematuria in a good number of cases with variable response to steroid therapy. There is a definite role for the usage of cytotoxic drugs in steroid resistant cases. Outcome of malignant FSGS is very poor. However, with the advent of cyclosporine, the outlook for these patients might change in the future. For better documentation and establishment of prognosis and outcome a long-term prospective study is suggested.

 
   References Top

1.Rich AR. A hitherto undescribed vulnerability to the juxtamedullary glomeruli in the lipoid nephro-sis. Bull Johns Hopkins Hosp 1957;100:173-5.  Back to cited text no. 1  [PUBMED]  
2.Cameron JS, Ogg CS, Turner DR, Weller OR. Focal glomerulosclerosis. In: Kincaid Smith, Mathew, Becker (eds). Glomerulonephritis. New- York: Widely 1973:249-61.  Back to cited text no. 2    
3.Jenis EH, Teichman S, Briggs WA, et al. Focal segmental glomerulosclerosis. Am J Med 1974;57:695-705.  Back to cited text no. 3  [PUBMED]  
4.Cameron JS. The problem of focal segmental glomerulosclerosis. In: Kincaid Smith D'Apice AJF, Atkins RC (eds). Progress in Glomerulonephritis. New York: John Wiley & Sons, 1979:209.  Back to cited text no. 4    
5.Glassock RJ, Adler SG, Ward HJ, Cohen AH. Primary glomerular diseases. In: Brenner BM, Rector FC Jr (eds). The Kidney, Philadelphia: WB Saunders, 1986:929.   Back to cited text no. 5    
6.Arbus GS, Poucell S, Bacheyie GS, Baumal R. Focal segmental glomerulosclerosis with idiopathic nephrotic syndrome: three types of clinical response. J Pediatr 1982; 101:40-5.   Back to cited text no. 6  [PUBMED]  
7.Hoyer JR. Focal segmental glomerulosclerosis. Sem Nephrology 1982;2:253.  Back to cited text no. 7    
8.Griswold WR, Tune BM, Reznik VM, et al. Treatment of childhood prednisoneresistant nephrotic syndrome and focal segmental glomerulo sclerosis with intravenous methylprednisolone and oral alkylating agents. Nephron 1987;46:73-7.  Back to cited text no. 8  [PUBMED]  
9.Brown CB, Cameron JS, Turner DR, et al. Focal segmental glomerulosclerosis with rapid decline in renal function ("malignant FSGS"). Clin Nephrology 1978;10:51-61.  Back to cited text no. 9    
10.Anderson RP, Bonchek LI, GrunKemeier GL, Lambert LE, Starr A. The analysis and presentation of surgical results by actuarial methods. J Surg Res 1974;16:224-30.  Back to cited text no. 10  [PUBMED]  [FULLTEXT]
11.Churg J, Habib R, White RH. Pathology of the nephrotic syndrome in children: a report for the International Study of Kidney Disease in Children. Lancet 1970;760:1299-302..  Back to cited text no. 11  [PUBMED]  
12.Habib R, Gubler MC. Focal glomerular lesions in idiopathic nephrotic syndrome of childhood. Observations of 49 cases. Nephron 1971:8:382-401.   Back to cited text no. 12    
13.Beaufils H, Alphonse JC, Guedon J, Legrain M. Focal glomerulosclerosis: natural history and treatment. A report of 70 cases. Nephron 1978;21:75-85.  Back to cited text no. 13    
14.Jennette JC. Evolution of mesangial IgM nephro-pathy into focal segmental glomerulosclerosis. Am J Nephrology 1981;1:222.  Back to cited text no. 14    

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Correspondence Address:
R G Singh
Consultant Nephrologist, King Fahd Specialist Hospital, P.O. Box 2290, Buraidah, Al-Gassim
Saudi Arabia
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PMID: 18583764

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