FSGS is caused by podocyte loss and is mostly a progressive glomerular disease (13, 14). Renal outcome is very diverse and progression to advanced kidney failure is common (15, 16).
In the present study we assessed the predictors of CKD/ESKD in patients with primary FSGS. Forty- five percent of our patients did not respond to treatment and 41% developed CKD or ESKD. The link between remission and renal survival was very high and 90% of patients without remission developed CKD/ESKD. In a study by Chun et al. the 10 years' kidney survival rates of patients with FSGS was 92% in patients with remission compared to 33% in those without remission (2).
Despite including 6 patients younger than 18 years, the demographics of our patients are almost similar to other studies of adult FSGS, with a mean age of 38±15 years in our study and an age at diagnose of 35-50 years old in other studies (11, 15).The prevalence of idiopathic FSGS was somewhat more in men in our study similar to others (14, 17).
Most of the patients in this study had mild renal impairment at baseline (MDRD eGFR: 65±38 ml/min/1.73m2). Renal function at admission is very diverse in adult primary FSGS but it is mostly reported as mild to moderate renal dysfunction at admission (18, 19). Our finding like others showed higher renal function at admission was positively related to better renal outcome (2, 20).
In our study the most prevalent variant of FSGS was NOS (68%), followed by tip lesion (22%), perihilar (6%), collapsing (3%), and cellular types (1%). Demographic features are different between various histologic subtypes of FSGS. Collapsing lesion has been reported with a higher prevalence in Afro-American patients and both tip lesion and collapsing variants have been more common in teenagers and adults compared to children (11, 12, 21).
Most studies have reported NOS variant as the most prevalent type of FSGS which is similar to our study (12, 21). However it is suggested that longer duration of FSGS may be correlated with NOS variant, probably due to evolution of segmental sclerosing lesions from tip lesion over time, as a part of chronicity process (22).
Regarding renal outcome, collapsing lesion has been associated with worst renal outcome and more common in non-responders (23). In our study all of the seven patients with collapsing lesion developed CKD/ESRD, including the two patients who ended in dialysis.
Tip lesion variant has been associated with a significantly better kidney survival (24, 25). Among 44 patients with tip lesion, only two did not attain complete or partial remission and developed CKD. In the current study 58% of patients with NOS did not response to treatment and more than half (52%) developed CKD/ESRD, which shows a worse prognosis in our NOS patients compared to other studies (11, 21, 26). This may have been the center effect and due to referral of more complicated patients to our kidney hospital, the effect of later referral compared to the mentioned studies or a basically different epidemiology of the disease in our country, which needs further investigation. Of the eleven patients with perihilar lesion, two progressed to CKD (18%) and were defined as non-responder. In the study by Thomas et al the patients with perihilar variant had good renal survival at 1 year (89%) and 3 years (75%) (21).
In our study the only two cases of cellular variant attained complete remission. In other studies cellular variant shows an intermediate prognosis between the two variants of collapsing and tip lesion (21). The low number of patients with cellular lesion in the present study does not let us to have any hard conclusions.
We showed that in the collapsing variant the risk of CKD/ESKD is significantly high in univariate analyses, however after adding IF/TA score in the adjusted multivariate model, this risk was no longer significant. So the high frequency of bad outcome in collapsing FSGS may be due to higher chronicity at diagnosis and this should be noticed and examined in other series.
There are some limitations in using Columbia classification as a predictor of clinical outcome. Different location of segmental lesions makes overlapping and heterogeneity between variants, which can lead to misdiagnosis by kidney biopsy (27-29). The accuracy of diagnosis highly depends on the number of glomeruli and sample size in biopsy (30, 31).
We showed that high IF/TA score at diagnosis strongly predicted the risk of CKD/ESKD in primary FSGS. The term interstitial fibrosis/tubular atrophy was first introduced in kidney allograft biopsy (32, 33).However today it is used as a predictor for progression of kidney failure, regardless of the type of the glomerular disease and interstitial fibrosis and tubular atrophy are well identified hallmarks for development of CKD (34-36)
The presence of global and segmental sclerosis in kidney biopsy indicates worse prognosis in kidney survival (4, 37). Global sclerosis is highly age-related and segmental sclerosis is the most important pathological finding in the typical FSGS (38). In this study we used the percentage of segmental sclerosis in the biopsy specimen as a predictor. Our finding showed that the higher number of glomeruli with segmental sclerosis on biopsy highly predicts the risk of CKD/ESKD.
In this study baseline proteinuria was not associated with increase in the risk of CDK/ESKD. This finding is contrary to the previous finding of proteinuria as an important risk factor for development of renal failure (39, 40).On the other hand in a very recent study on 466 patients with primary FSGS and proteinuria, followed for 1,4 and 8 months, by using a novel definition of remission, reduction of proteinuria was associated with better long-term renal outcomes(41). In a sub-analysis in our patients (not shown), greater decrease of proteinuria between baseline and last proteinuria was associated with decreased risk of CKD/ESRD [multivariate analysis (HR: 0.92, 95% CI 0.86-0.97)].
This study has several limitations. Since this is an observational study,
a cause–effect relationship cannot be established. The patients were treated by different physicians and treatment protocols or follow-up time may have had an influence on outcome. Time from early clinical manifestation and renal biopsy is diverse and this can lead to time bias. Laboratory data were reported by different laboratories which may have slightly affected the accuracy of the data. However the major strengths of this cohort study are scale adequate number of patients with primary FSGS, good number of events, very few missing data and examination of all kidney biopsy samples by one expert pathologist.