Repeat kidney biopsy findings of lupus nephritis patients in clinical remission treated with Mycophenolate associated with Belimumab or Mycophenolate plus standard of care therapy. A "post-hoc" analysis of participants in the BLISS-LN and open label extension study belonging to a single center.

BACKGROUND: Lupus nephritis affects 40 to 70% of Systemic Lupus Erythematous(SLE) patients increasing their morbi-mortality; therefore, successful treatments are required to improve outcomes. RESEARCH DESIGN AND STUDY SAMPLE: In this paper 20 patients who participated in the BLISS LN trial at a single center (OMI) in Argentina were studied. All the patients continued Mycophenolate (MMF) treatment when the trial was finished and until a second biopsy was performed to determine the withdrawal of the immunosuppression according to the achieved clinical and histological response. Ten patients treated with MMF + Placebo versus 10 receiving MMF + Belimumab, were compared evaluating the complete clinical (CCR) and complete histological response (CHR) and the flares in each group. RESULTS: All the patients in the Belimumab group showed a CCR and 7 in the Placebo one; CHR was found in 9 and 5 patients of the Belimumab and Placebo group, respectively. None of the patients in the Belimumab group flared meanwhile two of the Placebo one did it. CONCLUSIONS: Although the number of patients is insufficient to be able to draw unquestionable conclusions, adding Belimumab to the standard of care treatment with MMF would seem to increase the possibility of achieving a CCR, CHR, and a lower rate of relapses during treatment and long follow-up.

Remission of lupus nephritis: the trajectory of histological response in successfully treated patients.

OBJECTIVE: This study investigated changes in kidney histology over time in patients with lupus nephritis (LN) undergoing immunosuppressive treatment. METHODS: Patients with proliferative±membranous LN were studied. After a diagnostic kidney biopsy (Bx1), patients had protocol biopsy 2 (Bx2) at 9 (6-15) months and protocol biopsy 3 (Bx3) at 42 (28-67) months. Kidney histological activity and chronicity indices (AI, CI) were measured. RESULTS: AI declined in a biphasic fashion, falling rapidly between Bx1 and Bx2 and then more slowly between Bx2 and Bx3. Patients were divided into those who achieved histological remission, defined as an AI=0 at Bx3 (group 1), and those with persistent histological activity (AI >0) at Bx3 (group 2). The early decline in AI was 1.6 times greater (95% CI 1.30, 1.91) in group 1 than group 2 (p=0.01). Between Bx2 and Bx3, the AI decline was 2.19-fold greater (95% CI 2.09, 2.29) in group 1 versus group 2 (p=7.34×10-5). Individual histological components of the AI resolved at different rates. Inflammatory lesions like glomerular crescents, karyorrhexis and necrosis mostly resolved by Bx2, whereas endocapillary hypercellularity, subendothelial hyaline deposits and interstitial inflammation resolved slowly, accounting for residual histological activity at biopsy 3 in group 2. In contrast, CI increased rapidly, by 0.15 units/month between Bx1 and Bx2, then plateaued. There were no differences in the rate of accumulation of chronic damage between group 1 and group 2. The increase in CI was significantly related to the severity of glomerular crescents (p=0.044), subendothelial hyaline deposits (p=0.002) and interstitial inflammation (p=0.015) at Bx1. CONCLUSIONS: LN histological activity takes months to years to resolve, providing a rationale for the need of long-term, well-tolerated maintenance immunosuppression. Despite responding, LN kidneys accrue chronic damage early during treatment. This finding provides an explanation for the association of chronic progressive kidney disease with recurrent episodes of LN.

The lupus nephritis management renaissance.

Over the past year, and for the first time ever, the US Food and Drug Administration approved 2 drugs specifically for the treatment of lupus nephritis (LN). As the lupus community works toward understanding how to best use these new therapies, it is also an ideal time to begin to rethink the overall management strategy of LN. In addition to new drugs, this must include how to use kidney biopsies for management and not just diagnosis, how molecular technologies can be applied to interrogate biopsies and how such data can impact management, and how to incorporate LN biomarkers into management paradigms. Herein, we will review new developments in these areas of LN and put them into perspective for disease management now and in the future.

Kidney biopsy-based management of maintenance immunosuppression is safe and may ameliorate flare rate in lupus nephritis.

The optimal duration of maintenance immunosuppressive therapy for patients with lupus nephritis who have achieved clinical remission has not been established. Furthermore, clinical and histologic remissions are often discordant. We postulated that continuing therapy for patients with persistent histologic activity on kidney biopsies done during maintenance and discontinuing therapy only for patients without histologic activity would minimize subsequent lupus nephritis flares. To test this, a cohort of 75 prospectively-followed patients with proliferative lupus nephritis was managed using kidney biopsies performed during maintenance therapy. These patients had been on immunosuppression for at least 42 months, had responded, and had maintained their clinical response for at least 12 months before the kidney biopsy was repeated. Maintenance therapy was withdrawn if the biopsy showed an activity index of zero, but was continued if the biopsy showed an activity index of one or more. A lupus nephritis flare developed in seven patients during the average 50 months from the third biopsy and the final clinic visit for a flare rate of 1.5/year; significantly less than reported flare rates. Baseline clinical parameters (serum creatinine, proteinuria) and serologic parameters (complement C3, C4 and anti-dsDNA) did not predict an activity index of zero on the third biopsy or who would have a lupus nephritis flare. No patients developed end-stage kidney disease. Four patients developed de novo chronic kidney disease. There were no serious adverse events related to biopsy. Thus, at an experienced center, biopsy-informed management of maintenance immunosuppression is safe and may improve the lupus nephritis flare rate compared to conventional clinical management.

Biopsias renales: experiencia de 9 años en el Hospital Fernández / Kidney autopsies: A 9 years experience in the "Fernandez Hospital"

Renal biopsy is a key procedure for the evaluation and management of the renal diseases, in order to establish a certainty diagnosis, to perform an adequate treatment and to determine the prognosis, while it results in a fundamental tool, but not all the medical centers have the necessary requeriments to carry them succesfully so that it can achieve the maximum benefit, lessen the posible complications, since as it is an invasive technique, always exists a certain risk inherent to the procedure, being the technique of choice the percutaneous renal biopsy guided by ultrasound. The aim of this report, is to know the incidence of the reanl pathology, in kidney biopsies in our Hospita, between July 2008 through July 2017, by mean of a descriptive and retrospective study. Two-thousands and eightsi-six reanl biopsies were analyzed in that period, and we analyzed the frequency of the disease diagnosed, the origin of the samples and thir quality, the age range of the population studied, as well as the complications of the method employed

Histologic versus clinical remission in proliferative lupus nephritis.

BACKGROUND: Treatment response in lupus nephritis (LN) is defined clinically, without consideration of renal histology. Few studies have systematically examined histologic responses to induction therapy. In LN patients who underwent protocol kidney biopsies after induction immunosuppression, we describe the renal histology of the second biopsy and correlate histologic activity and damage with short- and long-term kidney outcomes. METHODS: Patients with suspected LN were biopsied for diagnosis (Biopsy 1), and those with proliferative LN were rebiopsied after induction (Biopsy 2). Histologic activity and damage at each biopsy were calculated as the National Institutes of Health activity and chronicity indices. Complete and partial renal responses after induction and after long-term follow-up were determined clinically. RESULTS: One-third of patients who achieved a complete clinical response after induction had persistently high histologic activity, and 62% of patients who had complete histologic remission on rebiopsy were still clinically active. Chronic renal damage increased after induction even in complete clinical responders. Chronicity at Biopsy 2 associated with long-term kidney function and development of chronic kidney disease. CONCLUSIONS: Early clinical and histologic outcomes are discordant in proliferative LN, and neither correlates with long-term renal outcome. The kidney accrues chronic damage rapidly and despite clinical response in LN. Preservation of kidney function may require therapeutic targeting of both chronic damage and inflammation during LN induction treatment.

Nefropatía por IgA. revisión y conducta terapéutica a propósito de un caso clínico / Therapeutic management of an IgA nephropathy case and disease review

La Nefropatía por Inmunoglobulina A (NIgA), también conocida como enfermedad de Berger, fue descrita por primera vez en 1968 por Berger e Hinglais. Se trata de una enfermedad heterogénea, tanto desde el punto de vista clínico, como histológico, caracterizada por la presencia de depósitos mesangiales de IgA. La clínica de presentación es extremadamente variable, pudiendo manifestarse desde microhematuria aislada hasta un deterioro agudo de la función renal por una glomerulonefritis extracapilar superpuesta. Inicialmente se la consideraba una entidad de buen pronóstico, pero con el paso del tiempo y a partir de un mayor conocimiento de la NIgA, se constató que la realidad era otra y que del 20 al 30% de los pacientes a los 20 años evolucionaban a la insuficiencia renal crónica (IRC) terminal y otro 20% mostraba una pérdida significativa de la función renal. En el presente artículo se describe un caso clínico de un paciente en el que se detectan casualmente marcadores de daño renal en la orina, y en quien los hallazgos histológicos observados en la biopsia renal modificaron su pronóstico y la conducta terapéutica. A partir de este caso clínico se realiza una actualización sobre la Nefropatía por IgA

Inmunoglobulin A (NIgA) Nephropathy also known as Berger disease, was described for the first time in 1968 by Berger and Hinglais. It is a heterogeneous disease, not only from clinical point of view but also from the histologicalone. Characterized by the presence of IgA mesangials deposits. Clinical presentation is extremely variable and can vary from isolated microhematuria up to a severe damage of renal function due to superimposed extracapillary glomerulonephritis. Initially it was considered an entity with good prognosis, but over time and more knowledge about IgAN, it was shown that 20 to 30% of 20 years old patients evolved to end stage renal failure and other 20% had important renal function loss. In the present article we describe a case of a patient in whom we detected by chance renal damage markers in the urine, and then the histologic findings observed in renal biopsy, modified the prognosis and therapeutic procedure. From this clinical case, we performed an update on IgA Nephropathy

Use of enteric coated mycophenolate sodium in adult resistant nephrotic syndrome.

INTRODUCTION: Treatment of patients with resistant/relapsed adult nephrotic syndrome (RNS) caused by glomerulopathies has no consensus therapy. OBJECTIVES: This is a retrospective analysis (RA), performed on 55 patients with RNS treated during one year with enteric coated sodium mycophenolate (EC-MPS) and reduced corticosteroids doses. MATERIAL AND METHODS: Inclusion criteria for this RA were: patients aged ≥ 18 years old, diagnosed with RNS with histologically proven glomerulopathy who had received standard therapy with enalapril and/or losartan and 10 mg per day or 20 mg of prednisone every other day. NS was defined with the following criteria: proteinuria > 3.5 g/day, serum albumin ≤ 3 g/dl, hypercholesterolemia and edema. Treatment consisted of oral EC-MPS in 360 mg tablets, 720 mg bid, together with prednisone 10 mg daily or 20 mg every other day. Effectiveness was assessed as the rate of response in the cohort: complete, partial or absent. Complete response patients: 24 hours proteinuria < 300 mg/day, partial response patients: proteinuria > 300 mg/day and < than 3 g/day, all the rest were considered as non responders. RESULTS: response was achieved in 40/55 (73%) of patients, 24 (44%) with complete response and 16 (29%) with partial response. No EC-MPS discontinuation has been observed due to adverse events, except for one case of transient interruption of medication for 2 weeks. CONCLUSION: EC-MPS as single therapy with minimal doses of corticosteroids as in this RA could be an effective alternative in the treatment of patients with RNS.

Nefropatía por Ig A: Un caso que ilustra sus controversias / Ig A Nephropathy: A case that illustrates its controversies

La nefropatía por IgA (N IgA)es una glomerulonefritis que se caracteriza por evidenciar depósitos mesangiales difusos de IgA. Fue por primera vez descripta en 1968 por el patólogo francés Jean Berger, coincidiendo su aparición con la introducción de técnicas de inmunofluorescencia (IF) en las biopsias renales. De ahí el hecho de que esta patología sea conocida también como Enfermedad de Berger.La nefropatía por IgA es la única glomerulopatía que se define por la presencia de un tipo de depósito en la IF, más allá del patrón morfológico descripto en la biopsia. Los hallazgos en la microscopía óptica son tan variables que no permiten la elaboración de un score universal y a la vez determinar la correlación de la histopatología con la clínica.Durante muchos años la N IgA fue considerada una patología benigna. Hoy se sabe sin embargo que muchos casos evolucionan hacia la insuficiencia renal (hasta un 50%)... (AU)

IgA nephropaty (IgAN) is a mesangial proliferative glomerulonephritis characterized by diffuse mesangial deposition of IgA. IgAN is unique among glomerular diseases in being defined by the presence of an inmune reactant rather than by another morphologic feature found in renal biopsy. Light microscopic changes are so variable that there is no universal score and it is not possible to correlate pathology with clinical manifestations... (AU)

Nefropatía por Ig A: Un caso que ilustra sus controversias / Ig A Nephropathy: A case that illustrates its controversies

La nefropatía por IgA (N IgA)es una glomerulonefritis que se caracteriza por evidenciar depósitos mesangiales difusos de IgA. Fue por primera vez descripta en 1968 por el patólogo francés Jean Berger, coincidiendo su aparición con la introducción de técnicas de inmunofluorescencia (IF) en las biopsias renales. De ahí el hecho de que esta patología sea conocida también como Enfermedad de Berger.La nefropatía por IgA es la única glomerulopatía que se define por la presencia de un tipo de depósito en la IF, más allá del patrón morfológico descripto en la biopsia. Los hallazgos en la microscopía óptica son tan variables que no permiten la elaboración de un score universal y a la vez determinar la correlación de la histopatología con la clínica.Durante muchos años la N IgA fue considerada una patología benigna. Hoy se sabe sin embargo que muchos casos evolucionan hacia la insuficiencia renal (hasta un 50%)...

IgA nephropaty (IgAN) is a mesangial proliferative glomerulonephritis characterized by diffuse mesangial deposition of IgA. IgAN is unique among glomerular diseases in being defined by the presence of an inmune reactant rather than by another morphologic feature found in renal biopsy. Light microscopic changes are so variable that there is no universal score and it is not possible to correlate pathology with clinical manifestations...