Role of early repeated renal biopsies in lupus nephritis.
Zickert A,Sundelin B,Svenungsson E,Gunnarsson I
Lupus science & medicine
OBJECTIVES:A renal biopsy is generally recommended for diagnosis and is necessary for classification of lupus nephritis (LN), but second biopsies after immunosuppressive therapy are seldom a routine procedure. We investigated how repeat biopsies contribute to the evaluation of treatment response and long-term outcome in LN. METHODS:Sixty-seven patients with active LN were included. Renal biopsies were performed at diagnosis and after standard induction immunosuppressive therapy in all patients (median 8 months), regardless of clinical outcome. Biopsies were evaluated according to the International Society of Nephrology/Renal Pathology Society classification. Clinical response was defined as complete (CR), partial (PR) or non-response (NR) according to recent definitions. Histological response (HR) was defined as Class I, II or III/IV-C on repeat biopsies. Long-term renal outcome was determined in 55 patients after a median of 10 years. RESULTS:CR was demonstrated in 25%, PR in 27% and NR in 48% of patients. HR was shown in 42% and histopathological non-response (HNR) in 58% of patients. Twenty-nine per cent of CR and 61% of patients with PR had active lesions on repeat biopsies, that is, were HNR. Poor long-term renal outcome was associated with high chronicity index at repeated biopsies, but not with clinical or histological response. CONCLUSIONS:Despite apparent clinical response to immunosuppressive therapy, repeated biopsies revealed persisting active nephritis in almost half of the patients, thus providing additional information to clinical response criteria. Repeated renal biopsies may be a tool to improve the evaluation of treatment response in LN.
10.1136/lupus-2014-000018
[The repeated biopsy in patients with lupus nephritis].
Subils Gisella,Alba Paula,Gobbi Carla,Astesana Pablo,Babini Alejandra,Albiero Eduardo
Revista de la Facultad de Ciencias Medicas (Cordoba, Argentina)
We retrospectively studied patients with SLE according to ACR criteria, with NL who underwent a repeat renal biopsy from 2005 to 2012. We analyzed the main indications of renal biopsies, the histopathological Class and activity and chronicity changes. RESULTS The total number of patients with NL was 120, of which 18 (15%) patients underwent repeat renal biopsy, 18 had 2 renal biopsies and 6 had 3 biopsies. 3 (16.7%) patients were smokers; 1 (5.6%) had a history of previous DBT, 2 (11.1%) had a history of hypertension; and 3 (16.7%) patients had previous obesity. The duration of SLE was 15 ± 96 months; the time between the 1st and the 2nd biopsy was 45 ± 11 months and the time between the 2nd and 3rd biopsy was 56 ± 12 months. Indications for repeat biopsy were proteinuria in 10 biopsies (41.6%); proteinuria with impaired renal function in 2 biopsies (8.3%); proteinuria with pathological urine sediment in 8 (33.3%); . and pathological proteinuria with pathological urine sediment and impaired renal function in 4 biopsies (16.6%) The most frequent histological changes found between first and repeat biopsies were class IV to class III: 2 (8.2%) ; Class IV to Class IV: 8 (33.3%), class IV to class III + V: 2 (8.2%); class IV to class IV + V 3 (12.5%); class IV to class V: 2 (8.2%). Changes in NL biopsies with proliferative activity and chronicity indices (A / C) were: A to A / C: 7 (29.1%), A / C to A / C: 7 (29.1%). The immunosuppressive therapy was increased in 79.1% and 16.6% remained without changes. 20% patients received cyclophosphamide 1 g every 30 days, 26% Cyclophosphamide 500 mg every 15 days, 23% induction therapy with mycophenolate mofetil; 23% with Rituximab; 8% Cyclosporin A. Maintenance therapy with mycophenolate mofetil was performed in 87.5%; azathioprine in 1 case. Hydroxychloroquine was used in all cases.
Immune gene expression in kidney biopsies of lupus nephritis patients at diagnosis and at renal flare.
Mejia-Vilet Juan M,Parikh Samir V,Song Huijuan,Fadda Paolo,Shapiro John P,Ayoub Isabelle,Yu Lianbo,Zhang Jianying,Uribe-Uribe Norma,Rovin Brad H
Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association
BACKGROUND:Up to 50% of lupus nephritis (LN) patients experience renal flares after their initial episode of LN. These flares contribute to poor renal outcomes. We postulated that intrarenal immune gene expression is different in flares compared with de novo LN, and conducted these studies to test this hypothesis. METHODS:Glomerular and tubulointerstitial immune gene expression was evaluated in 14 patients who had a kidney biopsy to diagnose LN and another biopsy at their first LN flare. Ten healthy living kidney donors were included as controls. RNA was extracted from laser microdissected formalin-fixed paraffin-embedded kidney biopsies. Gene expression was analyzed using the Nanostring nCounter® platform and validated by quantitative real-time polymerase chain reaction. Differentially expressed genes were analyzed by the Ingenuity Pathway Analysis and Panther Gene Ontology tools. RESULTS:Over 110 genes were differentially expressed between LN and healthy control kidney biopsies. Although there was considerable molecular heterogeneity between LN biopsies at diagnosis and flare, for about half the LN patients gene expression from the first LN biopsy clustered with the repeated LN biopsy. However, in all patients, a set of eight interferon alpha-controlled genes had a significantly higher expression in the diagnostic biopsy compared with the flare biopsy. In contrast, nine tumor necrosis factor alpha-controlled genes had higher expression in flare biopsies. CONCLUSIONS:There is significant heterogeneity in immune-gene expression of kidney tissue from LN patients. There are limited but important differences in gene expression between LN flares, which may influence treatment decisions.
10.1093/ndt/gfy125
Repeated Renal Biopsy - A Predictive Tool to Assess the Probability of Renal Flare in Lupus Nephritis.
Piñeiro Gastón J,Arrizabalaga Pilar,Solé Manel,Abellana Rosa M,Espinosa Gerard,Cervera Ricard
American journal of nephrology
BACKGROUND:How one responds to treatment of lupus nephritis (LN) is based on clinical features, but the activity in renal biopsy (RB) is uncertain. We have described the therapeutic decisions after performing a repeated RB on the assessment of response to intravenous cyclophosphamide (IC) and the possible prognostic role of this repeated RB. METHODS:Clinical, laboratory and histological features at the initial RB and repeated RB were analyzed in 35 patients. RESULTS:Data in the initial versus the repeated RB were serum creatinine 1.23 ± 1.08 and 0.96 ± 0.45 mg/dl (p < 0.05), glomerular filtration rate <60 ml/min in 12 and 5% patients and proteinuria 4.1 ± 2.8 vs. 0.6 1.1 g/day (p < 0.05). Significant differences were detected in hematuria, nephrotic syndrome and serological immune features. Complete renal remission was reached in 60% (n = 21) at the time of the repeated RB, partial remission in 31.4% (n = 11), and no response IC in 8.6% (n = 3). Nine patients showed proliferative forms in the repeated RB, 3 of them had proteinuria <1 g/day. Just after the repeated RB, 34.3% increased or started a new immunosuppressive therapy, 17.1% remained with the same complementary IST, and 14.3% decreased or stopped it. In the follow-up post repeated RB, 34.5% without active lesions showed a renal flare versus 77.8% with active lesions (p = 0.04). The mean time was 120 and 45 months, respectively. CONCLUSION:A repeated biopsy in LN distinguishes patients in true remission from those in apparent remission. By doing this, we can identify patients who could benefit from intensified treatment and for whom unnecessary treatment methods can be modified or eliminated.
10.1159/000452229
The clinical relevance of repeat renal biopsies in the management of lupus nephritis: a South African experience.
Tannor E K,Bates W D,Moosa M R
Lupus
Purpose Clinically, repeat renal biopsies (RRBs) have been performed in lupus nephritis to identify changes in class, plan treatment and assist in prognostication. We set out to compare the histopathological features and outcomes of disease flare and protocol biopsy patients. Methods A retrospective descriptive study was conducted on repeat biopsies performed between January 1984 and December 2015 in lupus nephritis patients. Disease flares and protocol biopsies were compared. Results Of 614 systemic lupus erythematosus (SLE) renal biopsies, 127 (20.7%) RRBs were identified. Disease flare patients accounted for 96 (75.6%) and protocol biopsies for 31 (24.4%) of RRBs. Seventy (72.9%) disease flare patients retained their original class on repeat biopsy. When categorised as proliferative and non-proliferative histology, 83 (87.4%) of the disease flare biopsy patients remained histologically unchanged. Treatment remained unchanged in 57 (60.0%) patients following RRBs for disease flares. Response to immunosuppression in disease flare patients was poorer. Non-response was associated with increased chronicity index (OR = 1.33; 95% CI 1.01-1.76; p = 0.045). Thirty-three (36.3%) disease flare patients developed end-stage kidney disease (ESKD) in one year as compared to one (3.6%) protocol biopsy patient ( p = 0.003). ESKD in disease flare patients was associated with non-response to treatment (OR = 24.6; 95% CI 2.7-219.3; p = 0.004) on multivariate analysis. One-year mortality was 30.0% in the disease flare patients and 3.5% in protocol biopsy patients ( p = 0.018). Conclusion Repeat biopsies in disease flare patients infrequently led to histological class changes, failed to lead to change of treatment in the majority of patients, and were associated with poorer outcomes.
10.1177/0961203317726864
Clinico-pathological features of repeat renal biopsies in patients with lupus nephritis at Groote Schuur Hospital, Cape Town.
Kajawo S,Botha F C J,Okpechi I G
Lupus
Background Repeat renal biopsies in patients with lupus nephritis are usually done to guide treatment or to establish disease chronicity. Their value is not clear from available literature. There are also no available data in Africa to guide clinicians. Methods This was a retrospective study of patients undergoing a repeat renal biopsy between January 2003 and December 2014 from a single centre in Cape Town, South Africa. Relevant demographic, clinical and histological records of patients with repeat renal biopsies were documented. Comparison of data from first and second renal biopsy was performed. Results Forty-four patients had at least two biopsies done during the study period. Most patients were females (81.8%). The mean biopsy interval was 2.8 ± 1.8 (range 0.38-9.4) years. Proteinuria was the main indication for the repeat biopsy (36.1%). The glomerular filtration rate and proteinuria worsened between the two biopsies ( p = 0.001 and 0.019, respectively) suggesting disease progression. Most patients (65.4%) with a non-proliferative class of lupus nephritis at first biopsy progressed into a proliferative class, whereas patients with initial proliferative lupus nephritis at first biopsy (77.8%) remained as proliferative at repeat biopsy. Treatment was changed in 85% of patients at second biopsy. Conclusion Repeat renal biopsies in patients with lupus nephritis presents a useful means of assessing disease progression and provides guidance regarding modification of treatment. More studies are, however, required to evaluate the value of repeat biopsies and perhaps the need for protocol renal biopsies in patients with lupus nephritis.
10.1177/0961203317695466