[Lupus nephritis and thrombotic microangiopathy: A review].

Lupus nephritis (LN) is one of the most common organ-specific manifestations of systemic lupus erythematosus (SLE). Various clinical signs of LN develop in at least 50% of patients with SLE. In addition to LN, the spectrum of renal lesions associated with SLE also includes vascular pathology. One of the variants of renal microvascular injury is thrombotic microangiopathy (TMA), the mechanisms of which are diverse. The review focuses on the main forms of TMA, including antiphospholipid syndrome and nephropathy associated with antiphospholipid syndrome, TMA caused by complement system regulation disorders and deficiency of ADAMTS13. In most cases, these forms of TMA are combined with LN. However, they may also exist as a single form of kidney damage. This article discusses the TMA pathogenesis, the impact on kidney prognosis, and treatment options.

Renal arterial resistive index as a prognostic marker in lupus nephritis patients.

INTRODUCTION: Lupus nephritis (LN) is known to be one of the most serious complications of SLE and it is a major predictor of poor prognosis. Despite the improvement in understanding the pathophysiology of lupus nephritis and greater improvement in diagnostic approaches, lupus nephritis patients have poorer outcomes. OBJECTIVES: Study the relation between renal resistive index (RRI) and renal function and histopathological parameters in lupus nephritis (LN) patients. Also to investigate the usefulness of RRI in predicting response to treatment. PATIENTS AND METHODS: This study included 126 patients who were split into two groups (group 1: 101 LN patients and group 2: 25 SLE patients without renal affection); and 100 healthy controls (group 3). The RRI was measured for all participants through a colored Doppler ultrasound examination. LN patients underwent renal biopsy and received their therapy and were followed up for 6 months. RESULTS: The RRI was significantly greater in the LN group (mean±SD; 0.64±0.07) than in SLE patients without nephritis (0.5884±0.04) (P<0.0001). The RRI was greater in LN class IV (P<0.0001). RRI significantly correlated with the chronicity index (r=0.704, P<0.0001), activity index (r=0.310, P=0.002), and serum creatinine (r=0.607, P<0.0001) and negatively correlated with eGFR (r=-0.719, P<0.0001). Almost eighty-five percent (84.8%) of LN patients responded to induction therapy. RRI was significantly greater in the nonresponder group (mean±SD, 0.73±0.02) than that in the responder group (0.63±.07) (P<0.0001). All non-responders to induction therapy while only 29.8% of responders had an RRI of ˃0.7. RRI, according to regression analysis was a significant predictor of response to treatment in LN patients. CONCLUSION: RRI was significantly greater in the LN group and significantly correlated with kidney function and histopathological parameters. RRI can predict response to induction therapy in LN patients.

Prevalence, Predictors, and Outcomes of Pulmonary Hypertension in Patients with Lupus Nephritis.

Background and Objectives: This study aimed to assess the prevalence, predictors, and outcomes of pulmonary hypertension (PH) in patients with lupus nephritis (LN). Materials and Methods: Baseline characteristics and clinical outcomes of 387 patients with LN were retrospectively collected from 2007 to 2017. PH was defined as pulmonary artery systolic pressure ≥40 mmHg assessed by resting transthoracic echocardiography. The primary endpoint was all-cause mortality. The secondary endpoint was renal events, defined as the doubling of baseline serum creatinine or end-stage renal disease. Associations between PH and outcomes were analyzed by Cox regression models. Results: A total of 15.3% (59/387) of patients with LN were diagnosed with PH, and the prevalence of PH was higher for patients with an estimated glomerular filtration rate (eGFR) < 30 mL/min/1.73 m2 compared to those with an eGFR ≥ 30 mL/min/1.73 m2 (31.5% vs. 12.6%). Higher mean arterial pressure, lower hemoglobin, and lower triglyceride levels were associated with greater odds of having PH. After adjusting for relevant confounding variables, PH was independently associated with a higher risk for death (HR: 2.01; 95% CI: 1.01-4.00; p = 0.047) and renal events (HR: 2.07; 95% CI: 1.04-4.12; p = 0.039). Conclusions: PH is an independent risk factor for all-cause mortality and adverse renal outcomes in patients with LN.

Characterizing Glomerular Barrier Dysfunction with Patient-Derived Serum in Glomerulus-on-a-Chip Models: Unveiling New Insights into Glomerulonephritis.

Glomerulonephritis (GN) is characterized by podocyte injury or glomerular filtration dysfunction, which results in proteinuria and eventual loss of kidney function. Progress in studying the mechanism of GN, and developing an effective therapy, has been limited by the absence of suitable in vitro models that can closely recapitulate human physiological responses. We developed a microfluidic glomerulus-on-a-chip device that can recapitulate the physiological environment to construct a functional filtration barrier, with which we investigated biological changes in podocytes and dynamic alterations in the permeability of the glomerular filtration barrier (GFB) on a chip. We also evaluated the potential of GN-mimicking devices as a model for predicting responses to human GN. Glomerular endothelial cells and podocytes successfully formed intact monolayers on opposite sides of the membrane in our chip device. Permselectivity analysis confirmed that the chip was constituted by a functional GFB that could accurately perform differential clearance of albumin and dextran. Reduction in cell viability resulting from damage was observed in all serum-induced GN models. The expression of podocyte-specific marker WT1 was also decreased. Albumin permeability was increased in most models of serum-induced IgA nephropathy (IgAN) and membranous nephropathy (MN). However, sera from patients with minimal change disease (MCD) or lupus nephritis (LN) did not induce a loss of permeability. This glomerulus-on-a-chip system may provide a platform of glomerular cell culture for in vitro GFB in formation of a functional three-dimensional glomerular structure. Establishing a disease model of GN on a chip could accelerate our understanding of pathophysiological mechanisms of glomerulopathy.

Circadian rhythms and renal pathophysiology.

The reality of life in modern times is that our internal circadian rhythms are often out of alignment with the light/dark cycle of the external environment. This is known as circadian disruption, and a wealth of epidemiological evidence shows that it is associated with an increased risk for cardiovascular disease. Cardiovascular disease remains the top cause of death in the United States, and kidney disease in particular is a tremendous public health burden that contributes to cardiovascular deaths. There is an urgent need for new treatments for kidney disease; circadian rhythm-based therapies may be of potential benefit. The goal of this Review is to summarize the existing data that demonstrate a connection between circadian rhythm disruption and renal impairment in humans. Specifically, we will focus on chronic kidney disease, lupus nephritis, hypertension, and aging. Importantly, the relationship between circadian dysfunction and pathophysiology is thought to be bidirectional. Here we discuss the gaps in our knowledge of the mechanisms underlying circadian dysfunction in diseases of the kidney. Finally, we provide a brief overview of potential circadian rhythm-based interventions that could provide benefit in renal disease.

B-cell depletion with obinutuzumab for the treatment of proliferative lupus nephritis: a randomised, double-blind, placebo-controlled trial.

OBJECTIVE: Randomised trials of type I anti-CD20 antibodies rituximab and ocrelizumab failed to show benefit in proliferative lupus nephritis (LN). We compared obinutuzumab, a humanised type II anti-CD20 monoclonal antibody that induces potent B-cell depletion, with placebo for the treatment of LN in combination with standard therapies. METHODS: Patients with LN receiving mycophenolate and corticosteroids were randomised to obinutuzumab 1000 mg or placebo on day 1 and weeks 2, 24 and 26, and followed through week 104. The primary endpoint was complete renal response (CRR) at week 52. Exploratory analyses through week 104 were conducted. The prespecified alpha level was 0.2. RESULTS: A total of 125 patients were randomised and received blinded infusions. Achievement of CRR was greater with obinutuzumab at week 52 (primary endpoint, 22 (35%) vs 14 (23%) with placebo; percentage difference, 12% (95% CI -3.4% to 28%), p=0.115) and at week 104 (26 (41%) vs 14 (23%); percentage difference, 19% (95% CI 2.7% to 35%), p=0.026). Improvements in other renal response measures, serologies, estimated glomerular filtration rate and proteinuria were greater with obinutuzumab. Obinutuzumab was not associated with increases in serious adverse events, serious infections or deaths. Non-serious infusion-related reactions occurred more frequently with obinutuzumab. CONCLUSIONS: Improved renal responses through week 104 were observed in patients with LN who received obinutuzumab plus standard therapies compared with standard therapies alone. Obinutuzumab was well tolerated and no new safety signals were identified. TRIAL REGISTRATION NUMBER: NCT02550652.

Comparison of renal remission and relapse-free rate in initial- and delayed-onset lupus nephritis.

INTRODUCTION: Lupus nephritis (LN) is a major manifestation of systemic lupus erythematosus (SLE) which contributes to significant morbidity and mortality. It is unclear whether the timing of LN onset influences renal outcome. This study aimed to investigate differences in clinical features-particularly the relapse-free rate-in remission duration from induction therapies for LN and the onset timing of LN after the development of SLE. METHODS: We enrolled 66 LN patients from January 2004 to March 2020. We collected the following: demographic data, laboratory data, renal histology data, and LN induction therapy data. Renal remission and relapse-free rates were calculated for each group. RESULTS: Patients were first divided into early remission group (achieved renal remission in <12 months [n = 44]) and others (n = 22). There were no significant differences in clinical data, treatments, and relapse-free rate of LN. Patients were then divided into initial-onset LN (<12 months after development of SLE [n = 49]) and delayed-onset LN (≥12 months after development of SLE [n = 17]). Kaplan-Meier analysis showed that the relapse-free rate was significantly higher in all patients with initial-onset LN than those with delayed-onset LN (P = .0094). CONCLUSION: The relapse-free rate was significantly higher in the initial-onset LN group than the delayed-onset LN group of patients with LN of various histopathological backgrounds. These data suggest that delayed-onset LN is a risk factor for the relapse of LN.

Lupus podocytopathy superimposed on diabetic glomerulosclerosis: A case report.

RATIONALE: Lupus podocytopathy (LP) is an entity that is increasingly being reported in the literature on systemic lupus erythematosus (SLE). LP is characterized by nephrotic syndrome in SLE patients with diffuse glomerular podocyte foot process effacement and no immune complex deposits along the capillary loops. Histologically, LP typically mimics minimal change disease or primary focal segmental glomerulosclerosis (FSGS) on a background of ISN/RPS class I or II lupus nephritis. In situations where there are coexistent glomerular diseases, however, LP may be easily masked by background lesions and overlapping clinical symptoms. PATIENT CONCERNS: We report the case of a 24-year-old woman with type I diabetes, hypertension, psoriasis/rash, and intermittent arthritis who presented with abrupt onset of severe nephrotic proteinuria and renal insufficiency. Renal biopsy revealed nodular glomerulosclerosis and FSGS. Immune deposits were not identified by immunofluorescence or electron microscopy. Ultrastructurally, there was diffuse glomerular basement membrane thickening and over 90% podocyte foot process effacement. With no prior established diagnosis of SLE, the patient was initially diagnosed with diabetic nephropathy with coexistent FSGS, and the patient was started on angiotensin-converting enzyme inhibitors (ACEI) and diuretics. However, nephrotic proteinuria persisted and renal function deteriorated. The patient concurrently developed hemolytic anemia with pancytopenia. DIAGNOSES: Subsequent to the biopsy, serologic results showed positive autoantibodies against double strand DNA (dsDNA), Smith antigen, ribonucleoprotein (RNP), and Histone. A renal biopsy was repeated, revealing essentially similar findings to those of the previous biopsy. Integrating serology and clinical presentation, SLE was favored. The pathology findings were re-evaluated and considered to be most consistent with LP and coexistent diabetic nephropathy, with superimposed FSGS either as a component of LP or as a lesion secondary to diabetes or hypertension. INTERVENTIONS: The patient was started on high-dose prednisone at 60 mg/day, with subsequent addition of mycophenolate mofetil and ACEI, while prednisone was gradually tapered. OUTCOMES: The patient's proteinuria, serum creatinine, complete blood counts, skin rash, and arthritis were all significantly improved. CONCLUSION: The diagnosis of LP when confounded by other glomerular diseases that may cause nephrotic syndrome can be challenging. Sufficient awareness of this condition is necessary for the appropriate diagnosis and treatment.

Anifrolumab: First Approval.

Anifrolumab (anifrolumab-fnia; Saphnelo™) is a monoclonal antibody antagonist of the type 1 interferon receptor (IFNAR). It is being developed by AstraZeneca (under license from Medarex, now Bristol-Myers Squibb) for the treatment of autoimmune disorders, including systemic lupus erythematosus (SLE) and lupus nephritis, the underlying pathogenesis of which involves type 1 interferon. In July 2021, intravenous anifrolumab was approved in the USA for the treatment of adult patients with moderate to severe SLE who are receiving standard therapy. Anifrolumab (intravenous or subcutaneous) continues to be assessed in clinical studies in SLE in various countries, and the intravenous formulation is under regulatory review in the EU and Japan. This article summarizes the milestones in the development of anifrolumab leading to this first approval for the treatment of moderate to severe SLE.

Differences in rituximab use between pediatric rheumatologists and nephrologists for the treatment of refractory lupus nephritis and renal flare in childhood-onset SLE.

BACKGROUND: Consensus treatment plans have been developed for induction therapy of newly diagnosed proliferative lupus nephritis (LN) in childhood-onset systemic lupus erythematosus. However, patients who do not respond to initial therapy, or who develop renal flare after remission, warrant escalation of treatment. Our objective was to assess current practices of pediatric nephrologists and rheumatologists in North America in treatment of refractory proliferative LN and flare. METHODS: Members of Childhood Arthritis and Rheumatology Research Alliance (CARRA) and the American Society for Pediatric Nephrology (ASPN) were surveyed in November 2015 to assess therapy choices (other than modifying steroid dosing) and level of agreement between rheumatologists and nephrologists for proliferative LN patients. Two cases were presented: (1) refractory disease after induction treatment with corticosteroid and cyclophosphamide (CYC) and (2) nephritis flare after initial response to treatment. Survey respondents chose treatments for three follow up scenarios for each case that varied by severity of presentation. Treatment options included CYC, mycophenolate mofetil (MMF), rituximab (RTX), and others, alone or in combination. RESULTS: Seventy-six respondents from ASPN and foty-one respondents from CARRA represented approximately 15 % of the eligible members from each organization. Treatment choices between nephrologists and rheumatologists were highly variable and received greater than 50 % agreement for an individual treatment choice in only the following 2 of 6 follow up scenarios: 59 % of nephrologists, but only 38 % of rheumatologists, chose increasing dose of MMF in the case of LN refractory to induction therapy with proteinuria, hematuria, and improved serum creatinine. In a follow up scenario showing severe renal flare after achieving remission with induction therapy, 58 % of rheumatologists chose CYC and RTX combination therapy, whereas the top choice for nephrologists (43 %) was CYC alone. Rheumatologists in comparison to nephrologists chose more therapy options that contained RTX in all follow up scenarios except one (p < 0.05). CONCLUSIONS: Therapy choices for pediatric rheumatologists and nephrologists in the treatment of refractory LN or LN flare were highly variable with rheumatologists more often choosing rituximab. Further investigation is necessary to delineate the reasons behind this finding. This study highlights the importance of collaborative efforts in developing consensus treatment plans for pediatric LN.

Improvement of renal and non-renal SLE outcome measures on sirolimus therapy - A 21-year follow-up study of 73 patients.

The safety, tolerance, and selected renal and non-renal outcome measures were evaluated in 73 SLE patients who received sirolimus therapy for more than 3 months in our institution over the past 21 years. In 12 patients who had lupus nephritis, proteinuria (p = 0.0287), hematuria (p = 0.0232), anti-DNA antibody levels (p = 0.0028) and steroid use were reduced (p = 0.0200). In the non-renal cohort of 61 patients, anti-DNA antibody levels (p = 0.0332) and steroid use were reduced (p = 0.0163). Both in the renal and non-renal cohorts, C3 (renal p = 0.0070; non-renal p = 0.0021) and C4 complement levels were increased (renal p = 0.0063; non-renal p = 0.0042) Adverse effects of mouth sores (2/73), headaches (1/73), and gastrointestinal discomfort were noted in a minority of patients (6/73). Sirolimus was only discontinued in two of 73 patients due to headache and recurrent infections, respectively. This study suggests that sirolimus is well tolerated and exerts long-term therapeutic efficacy in controlling renal and non-renal manifestations of SLE.

Association of antiphospholipid antibodies with clinical activity and renal pathological activity in patients with lupus nephritis.

OBJECTIVES: This study aimed to investigate the association of antiphospholipid antibodies (aPL) with clinical activity and renal pathological activity in patients with lupus nephritis (LN). METHODS: Levels of anticardiolipin () antibodies, anti-ß2-glycoprotein I (anti-ß2-GPI) antibodies and lupus anticoagulant (LAC) were measured, and other clinical and pathological data were also obtained during the same period before renal biopsy. RESULTS: A total of 83 patients with LN were included in this study, 40 patients (48.2%) in the s positive group and 43 patients in the aPL negative group. LN patients with positive aPL had significantly higher SLEDAI (p = 0.012), more hematuria (p = 0.043), lower serum C3 (p = 0.003) and C4 (p = 0.014), and a higher pathological activity index (p = 0.012), more micro-thrombosis (p = 0.046) and more C3 deposits (p = 0.038) in the glomerulus than patients with negative aPL The level of IgG- was significantly correlated with SLEDAI and serum level of C3 (r = 0.44, p < 0.001; r = -0.39, p = 0.003, respectively). The level of IgM- was significantly correlated with SLEDAI, and serum levels of C3 and C4 (r = 0.27, p = 0.014; r = -0.22, p = 0.041; r = -0.23, p = 0.035, respectively). CONCLUSIONS: Our work suggests that aPL, especially, are correlated with both clinical activity and renal pathological activity in patients with LN.

Prediction Of Renal Flare In Adult Patients With Lupus Induced Nephritis.

BACKGROUND: The most common complication of SLE is lupus nephritis (LN) causing high morbidity and mortality. The routine biomarkers used for the diagnosis of LN do not have the ability to predict the worsening in renal disease activity. Thus, there is need of a new biomarker leading to detection of flare in LN. The objective of this study was to assess the role of urinary neutrophil gelatinase associated lipocalin (uNGAL) as a predictor of renal flare in patients with lupus nephritis. METHODS: Including a total of 84 subjects, 42 cases were lupus patients without renal involvement and 42 cases were lupus patients with nephritis (24 active nephritis and 18 inactive nephritis). The diagnosis of lupus nephritis was established on the basis of renal biopsy. uNGAL was estimated in both groups. RESULTS: This study revealed that the nephritis group had increased levels of uNGAL as compared to systemic erythematosus patients without having lupus nephritis (p-value <0.05). Patients with active nephritis had increased uNGAL levels as compared to patients with inactive nephritis. CONCLUSIONS: From the findings in our study, it can be stated that uNGAL can prove to be a noninvasive, reliable and sensitive biomarker to predict flare in cases of lupus nephritis.

Machine Learning for Prediction and Risk Stratification of Lupus Nephritis Renal Flare.

BACKGROUND: Renal flare of lupus nephritis (LN) is strongly associated with poor kidney outcomes, and predicting renal flare and stratifying its risk are important for clinical decision-making and individualized management to reduce LN flare. METHODS: We randomly divided 1,694 patients with biopsy-proven LN, who had achieved remission after treatment, into a derivation cohort (n = 1,186) and an internal validation cohort (n = 508), at a ratio of 7:3. The risk of renal flare 5 years after remission was predicted using an eXtreme Gradient Boosting (XGBoost) method model, developed from 59 variables, including demographic, clinical, immunological, pathological, and therapeutic characteristics. A simplified risk score prediction model (SRSPM) was developed from important variables selected by XGBoost model using stepwise Cox regression for practical convenience. RESULTS: The 5-year relapse rates were 39.5% and 38.2% in the derivation and internal validation cohorts, respectively. Both the XGBoost model and the SRSPM had good predictive performance, with a C-index of 0.819 (95% confidence interval [CI]: 0.774-0.857) and 0.746 (95% CI: 0.697-0.795), respectively, in the validation cohort. The SRSPM comprised 6 variables, including partial remission and endocapillary hypercellularity at baseline, age, serum Alb, anti-dsDNA, and serum complement C3 at the point of remission. Using Kaplan-Meier analysis, the SRSPM identified significant risk stratification for renal flares (p < 0.001). CONCLUSIONS: Renal flare of LN can be readily predicted using the XGBoost model and the SRSPM, and the SRSPM can also stratify flare risk. Both models are useful for clinical decision-making and individualized management in LN.

Elevated Creatinine Clearance in Lupus Nephritis patients with Normal Creatinine.

Objectives: The present study aimed to observe the differences in creatinine clearance (Ccr) in systemic lupus erythematosus (SLE) patients with normal serum creatinine at different levels of urinary protein. Method: The present cross-sectional study included 177 SLE patients with normal serum creatinine from Qilu Hospital of Shandong University between January 2010 and April 2020. The following data were collected: blood urea nitrogen (BUN), serum creatinine (Cr), serum total protein, serum albumin, immunoglobulin (Ig) G, IgA, IgM, complement 3, complement 4, anti-ds-DNA antibody, routine urine test, urine protein/creatinine ratio (UPCR) (g/g), and the SLE disease activity index. The estimated Ccr was calculated according to the Cockcroft formula. Results: 123 patients were with positive urinary protein (Lupus Nephritis, LN group) and 54 patients were with negative urinary protein (Non-LN group). Compared with the Non-LN group, the LN group had higher BUN (5.76±3.22 vs. 4.78±1.58, P=0.007) and Cr (62.36±19.53 vs. 54.83±11.09, P=0.001). There was a strong correlation between the UPCR and the semi-quantitative determination of urine protein in LN patients (r=0.9583, P=0.0417). The serum creatinine levels were significantly higher in patients with urine protein 3+ (72.97±25.16) or massive proteinuria (62.32±19.66) than the other groups. Patients with urinary protein ± exhibited a significantly elevated Ccr when compared to patients with urinary protein 3+ (130.6±44.15 vs. 110.5±33.50, P=0.02), and patients with UPCR<0.15 g/g had higher Ccr than other groups and showed significantly increased Ccr compared with patients with UPCR≥0.15 g/g (132.44±21.02 vs. 115.14±35.89, P=0.007). Conclusions: Early renal function impairment may be present in LN patients. The kidneys of LN patients with urinary protein ± or UPCR<0.15 g/g are in a state of hyperfunction.

Clinical and laboratory phenotypes in juvenile-onset Systemic Lupus Erythematosus across ethnicities in the UK.

Systemic lupus erythematosus (SLE) is a systemic autoimmune/inflammatory disease. Patients diagnosed with juvenile-onset SLE (jSLE), when compared to individuals with adult-onset SLE, develop more severe organ involvement, increased disease activity and greater tissue and organ damage. In adult-onset SLE, clinical characteristics, pathomechanisms, disease progression and outcomes do not only vary between individuals and age groups, but also ethnicities. However, in children and young people, the influence of ethnicity on disease onset, phenotype and outcome has not been investigated in detail. In this study, we investigated clinical and laboratory characteristics in pediatric SLE patients from different ethnic backgrounds (White Caucasian, Asian, Black African/Caribbean) accessing data from a national cohort of jSLE patients (the UK JSLE Cohort Study). Among jSLE patients in the UK, ethnicity affects both the disease's clinical course and outcomes. At diagnosis, Black African/Caribbean jSLE patients show more "classical" laboratory and clinical features when compared to White Caucasian or Asian patients. Black African/Caribbean jSLE patients exhibit more renal involvement and more frequently receive cyclophosphamide and rituximab. Studies targeting ethnicity-specific contributors to disease expression and phenotypes are necessary to improve our pathophysiological understanding, diagnosis and treatment of jSLE.

Low expression of estrogen receptor ß in renal tubular epithelial cells may cause hyperuricemia in premenopausal patients with systemic lupus erythematosus.

We investigated the impact of estrogen receptor (ER) expression in renal tubular epithelial cells on serum uric acid (UA) levels in premenopausal patients with systemic lupus erythematosus (SLE). Thirty patients underwent renal biopsy: 18 with SLE (LN group) and 12 with IgA nephritis (IgAN group). ERs (ERα and ERß) in renal tubular epithelial cells were measured using immunohistochemistry. The ER expression levels of the two groups were compared, and the relationship between the expression of ERs and serum UA levels was analyzed. Mean serum UA levels in the LN group were significantly higher than those of the IgA nephropathy group, while the mean creatinine levels and GFRs of the two groups were similar. Pathological changes in the LN group were significantly more severe than those in the IgAN group. ERß was expressed in renal tubular epithelial cells in both groups, but not in the glomeruli. ERß expression in the LN group was significantly lower than that in the IgAN group. ERß expression scores significantly negatively correlated with serum UA levels. These findings suggest that the expression of ERß in premenopausal female SLE patients may cause hyperuricemia, and may subsequently promote glomerular damage, suggesting that ERß may be involved in UA excretion.

What is the value of repeat kidney biopsies in patients with lupus nephritis?

INTRODUCTION: Recent studies with protocol biopsies have shown a mismatch between clinical and histological remission in lupus nephritis (LN). We aimed to evaluate histological changes in repeat kidney biopsies by clinical indication in patients with LN. METHODS: We analyzed 107 patients with LN in which a kidney biopsy was performed between 2008 and 2018. Of those, we included 26 (24.2%) who had ≥2 kidney biopsies. Classification was done according to the International Society of Nephrology/Renal Pathology Society. RESULTS: Mean time between biopsies was 71.5 ± 10.7 months. 73.1% of patients presented a change of class at repeat biopsy; 38.4% to a higher class and 34.6% to a lower class. A significant increase in glomerulosclerosis (% GS) (3.8% vs 18.7%, p = 0.006), interstitial fibrosis (3.8% vs 26.9%, p = 0.021), tubular atrophy (15.4% vs 57.7%, p = 0.001) and chronicity index (CI) (1 vs 3, p < 0.001) was observed at repeat biopsy. Subjects who developed chronic kidney disease progression had a lower rate of complete remission at 12 months (0% vs 37.5%, p = 0.02), higher % GS at first biopsy (7.9% vs 1.2%, p = 0.02) and higher CI (4 vs 2, p = 0.006), tubular atrophy (90% vs 37.6%, p = 0.008), interstitial fibrosis (50% vs 12.5%, p = 0.036) and vascular lesions (60% vs 18.8%, p = 0.031) at second biopsy. CONCLUSIONS: Our major finding was that patients with LN showed a significant increase in % GS, interstitial fibrosis, tubular atrophy and vascular lesions in repeat biopsies performed by clinical indication. This suggest that a second kidney biopsy may provide valuable and useful information regarding kidney disease progression.