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This study looked at the outcome of lupus nephritis in Asian Indians at a tertiary care university hospital. We found nephritis to be an early manifestation of SLE, with the majority of patients having proliferative nephritis. Survival with normal renal function was 84%, 69%, and 57% at 5, 10, and 15 years, respectively. In the worst-case scenario the figures are 77%, 63%, and 51%, respectively. There was no difference in outcome by histologic class of nephritis; however, patients who were not biopsied had a significantly worse outcome. The major risk factor for poor outcome was absence of remission at 1 year and occurrence of a major infection ever.
The young age at onset of nephritis in our series and female predominance is comparable to other studies (2, 4, 5, 7, 18–20). The majority had nephritis soon after the onset of lupus (median 1 year), similar to other studies reporting 50–68% as having nephritis at diagnosis of lupus (2, 4, 5, 18, 20). The most common histologic class was class IV, present in almost one-half of the patients, which is similar to other centers, including those in India (2, 8, 10, 11, 21–23). However, nearly one-fourth of our patients did not undergo a biopsy, which is higher than most other centers. One of the major reasons was lack of consent. We treated patients with standard regimens and the response was good, with 84.6% (worst case 75.4%) achieving remission at 1 year. This is comparable to previous studies reporting treatment response at 6 months to 1 year of 58–98% (11, 22, 24–27). However, our figures may be falsely high, as many patients lost to followup before 1 year (and not included) were in renal failure and would probably be nonresponders.
In our study, long-term survival with normal renal function was 84%, 69%, and 57% at 5, 10, and 15 years, respectively. In the worst-case scenario these figures are 77%, 63%, and 51%, respectively. This is lower than a previous study from Italy that found survival with normal renal function to be 90%, 86%, and 82% at 5, 10, and 15 years, respectively (4). However, that study was only on proliferative nephritis. Although not directly comparable, our figures are also lower than studies from Hong Kong that found “doubling of creatinine” only in 8.4% and 18.2% at 5 and 10 years, respectively (17). In our study, renal survival rates were 91%, 81%, and 76% at 5, 10, and 15 years, respectively. These figures in the worst-case scenario were 79%, 70%, and 66%, respectively. These are 10% lower compared to studies from the western-developed nations as well as Asian-developed countries such as Hong Kong and Japan (2, 3, 5–8). However, these are much better than those reported from our country previously. A study from South India found a 5-year renal survival rate of 65%, whereas another study from North India found 10-year survival to be 35% (9, 11). The worse outcome in those studies may be partly explained by the inclusion of patients with proliferative nephritis and pediatric patients. Also, both studies had a small sample size. We chose survival with normal renal function (and not renal survival) as the primary outcome, because in resource-poor settings such as ours, patients with renal failure are often lost to followup and few can afford renal replacement therapy.
This study did not find any disparities in outcomes of different histologic classes of nephritis. This is contrary to the traditional view of a worse prognosis for proliferative nephritis, with an increasing risk from class I to class VI, with the exception of class V (28, 29). Indeed, many studies have found proliferative lesions on biopsy or class IV to have a worse prognosis (2, 8, 10, 30, 31). However, there have been some studies that also did not find any differences in outcomes by class of nephritis (11, 21, 32). A possible explanation could be the improved outcomes in class IV (and class III) with current cytotoxic regimens (1). Also, tubulointerstitial inflammation rather than glomerular pathology may be an important determinant of prognosis, which we did not study (32). However, there may have been a true difference in outcomes that our study may not have detected due to smaller numbers in the nonproliferative classes. Also, there was a high proportion of nonbiopsied patients with a worse prognosis, and it is likely many of these would have proliferative nephritis if biopsied.
Factors associated with poor outcome were serum creatinine at onset, hypertension at onset, low C3 at onset, hematuria at onset, absence of remission at 1 year, and occurrence of or higher number of infections. Absence of remission and occurrence of a major infection remained significant on multivariate analyses. Failure of induction has consistently been the most important factor that determines prognosis in studies on outcomes including prospective trials, such as Euro-Lupus Nephritis Trial (3–7, 10, 17, 20). Similarly, many studies have found serum creatinine at onset and hypertension to be important prognostic factors (4, 6, 7, 17, 19). However, we did not find male sex, age at onset, or number of nephritic flares to be significant, unlike some studies (4, 5). In addition, we did not evaluate factors such as hematocrit, discoid lupus erythematosus, anti-Ro, and activity and chronicity scores found in other studies (2, 4, 5, 8, 10).
A unique risk factor for poor prognosis in our population was the occurrence of major infections. Infections as a sequel to immunosuppressive therapy were fairly common and occurred in nearly one-half of the patients. Compared to studies from other countries, the rate of infection in Indian SLE patients seems to be higher (4, 17, 22, 27). This seems to reflect the higher rate of both bacterial and mycobacterial infection in our center, with similar rates of viral infections such as zoster compared to other centers (4, 17, 22). The high occurrence of tuberculosis was similar to that reported from another study in India, probably reflecting high rates of tuberculosis in the general population (11). Infections were a common cause of death with tuberculosis being the most frequent, similar to an autopsy series from North India (33).
The limitations of our study are retrospective gathering of data and a high proportion of patients lost to followup. Although most patients with lupus nephritis in our country are referred to tertiary care, a referral bias toward more severe patients in our cohort cannot be ruled out. Also, a limitation is the lack of data on the compliance of patients with oral medicines or financial constraints causing dropout of treatment. We excluded patients biopsied elsewhere due to a lack of details of initial investigations and initial treatment given outside.
To conclude, this study found long-term outcomes in Asian Indians using standard immunosuppressive regimens to be 10% lower than western centers, but much better than those previously reported from India.