Immunosuppressive treatment results in patients with primary IgA nephropathy in Turkiye; the data from TSN-GOLD working group.

BACKGROUND: Immunoglobulin A (IgA) nephropathy (IgAN) treatment consists of maximal supportive care and, for high-risk individuals, immunosuppressive treatment (IST). There are conflicting results regarding IST. Therefore, we aimed to investigate IST results among IgAN patients in Turkiye. METHOD: The data of 1656 IgAN patients in the Primary Glomerular Diseases Study of the Turkish Society of Nephrology Glomerular Diseases Study Group were analyzed. A total of 408 primary IgAN patients treated with IST (65.4% male, mean age 38.4 ± 12.5 years, follow-up 30 (3-218) months) were included and divided into two groups according to treatment protocols (isolated corticosteroid [CS] 70.6% and combined IST 29.4%). Treatment responses, associated factors were analyzed. RESULTS: Remission (66.7% partial, 33.7% complete) was achieved in 74.7% of patients. Baseline systolic blood pressure, mean arterial pressure, and proteinuria levels were lower in responsives. Remission was achieved at significantly higher rates in the CS group (78% vs. 66.7%, p = 0.016). Partial remission was the prominent remission type. The remission rate was significantly higher among patients with segmental sclerosis compared to those without (60.4% vs. 49%, p = 0.047). In the multivariate analysis, MEST-C S1 (HR 1.43, 95% CI 1.08-1.89, p = 0.013), MEST-C T1 (HR 0.68, 95% CI 0.51-0.91, p = 0.008) and combined IST (HR 0.66, 95% CI 0.49-0.91, p = 0.009) were found to be significant regarding remission. CONCLUSION: CS can significantly improve remission in high-risk Turkish IgAN patients, despite the reliance on non-quantitative endpoints for favorable renal outcomes. Key predictors of remission include baseline proteinuria and specific histological markers. It is crucial to carefully weigh the risks and benefits of immunosuppressive therapy for these patients.

Cytoplasmic WT1 in IgA nephropathy, an indicator of poor prognosis associated with mesangial/peri-mesangial C4d.

BACKGROUND: We aimed to investigate the immuno-histochemical expression of C4d, ADAM10 and WT1 in kidney biopsies of immunoglobulin A nephropathy (IgAN) patients and correlate the findings with clinical, laboratory and histopathologic features in the hope of defining new parameters to better understand the pathogenesis of the disease, and predict prognosis. MATERIALS AND METHODS: Paraffin-embedded kidney biopsy samples of 128 IgAN patients were immuno-histochemically treated with C4d and ADAM10/WT1 dual stain. Results were evaluated according to Oxford classification parameters, epidemiologic features, laboratory findings at presentation and clinical follow-up. RESULTS: We observed C4d positivity in 40.6% of our patients, 25% of which was mesangial/peri-mesangial (m/pm) staining. Only m/pmC4d positivity statistically correlated with progression to end-stage renal disease (ESRD). M/pmC4d positive patients had statistically significantly higher baseline proteinuria levels, presence of crescents and > 25% segmental sclerosis of glomeruli. There was cytoplasmic staining of WT1 in 11.2% of cases. Presence of cWT1 correlated with m/pmC4d positivity and progression to ESRD. There was no glomerular ADAM10 detected and tubular expression of this protein did not relate to amount of tubular damage or other parameters. CONCLUSION: This study is the first to show that cWT1is involved in IgAN and appears as an independent variable for worse prognosis.

Dismal Prognosis of Acute Allergic Tubulointerstitial Nephritis in Patients with AA Amyloidosis.

INTRODUCTION: Patients with AA amyloidosis may present with acute kidney injury that progresses to end-stage kidney disease in a short period of time. Acute allergic tubulointerstitial nephritis (aTIN) is a frequent cause of acute kidney injury in patients with AA amyloidosis. Although aTIN has a favorable prognosis in the general population, the course of aTIN in patients with AA amyloidosis was not previously reported. In this retrospective study, we determined the prognosis of aTIN superimposed on AA amyloidosis. METHODS: Thirty-two patients with combined pathological diagnosis of AA amyloidosis + aTIN and 32 patients with isolated aTIN were compared in terms of 1-year renal functions after the biopsies were performed with an indication of acute kidney injury. Baseline renal functions and number of patients requiring hemodialysis at the time of biopsy was similar in both groups. RESULTS: At the end of the 12-month follow-up period, 29 of 32 patients in the amyloidosis + aTIN group and 1 of 32 patients in the isolated aTIN group required dialysis. Most of these patients with AA amyloidosis had completely normal renal function before the episode of acute kidney injury and had clear exposures to drugs associated with aTIN. CONCLUSION: In contrary to the patients without AA amyloidosis, patients with AA amyloidosis have extremely high risk of permanent renal failure in case of development of aTIN. Great caution should be exercised in prescribing drugs that are associated with aTIN, in patients with AA amyloidosis.

Baseline renal functions predict the effect of canakinumab on regression of proteinuria in patients with familial Mediterranean fever / Las funciones renales iniciales predicen el efecto del canakinumab en la regresión de la proteinuria en pacientes con fiebre mediterránea familiar

Introduction and objectives: Canakinumab, an IL-1 blocking drug, decreases the frequency and severity of the attacks and decreases the proteinuria level in colchicine resistant/intolerant familial Mediterranean fever (FMF) patients. However, it is not known whether patients with impaired or preserved renal functions respond differently to IL-1 blocking therapies in terms of proteinuria reduction and progression of kidney dysfunction which was the aim of this study. Materials and methods: Adult FMF subjects with biopsy proven amyloidosis who had 24-h urine protein excretion>150mg/day before initiation of canakinumab were divided into two groups as patients with preserved renal function (GFR≥60mL/min) and patients with impaired renal function (GFR<60mL/min). The response in proteinuria and renal functions are compared between two groups in this cross-sectional study. Results: A total of 18 patients (11 with preserved and 7 with impaired renal function) were included in this study. Although proteinuria levels of both groups were similar at the baseline and at six months after initiation of canakinumab, proteinuria at 12 months was significantly lower for patients with preserved renal function compared to patients with impaired renal function (2462±1760mg/day vs. 7065±3035mg/day respectively, p=0.02). All of the patients with preserved renal function had more than 50% decrease in proteinuria at 12 months compared to baseline values, while none of the patients with impaired renal function had more than 50% decrease in proteinuria. (AU)

Introducción y objetivos: El canakinumab, un fármaco bloqueante de la IL-1, disminuye la frecuencia y la gravedad de los ataques y reduce el nivel de proteinuria en pacientes con fiebre mediterránea familiar (FMF) resistentes o intolerantes a la colchicina. Sin embargo, se desconoce si los pacientes con función renal deteriorada o preservada responden de forma diferente a los tratamientos de bloqueo de la IL-1 en cuanto a la reducción de la proteinuria y la progresión de la disfunción renal, que era el objetivo de este estudio. Materiales y métodos: Los sujetos adultos con FMF y amiloidosis demostrada por biopsia que tenían una excreción de proteínas en orina de 24 h > 150 mg/día antes de iniciar el tratamiento con canakinumab, se dividieron en dos grupos: pacientes con función renal preservada (TFG ≥ 60 mL/min) y pacientes con función renal deteriorada (TFG < 60 mL/min). En este estudio transversal se comparan la respuesta en la proteinuria y las funciones renales entre dos grupos. Resultados: En este estudio se incluyeron 18 pacientes (11 con función renal preservada y siete con función renal deteriorada). Aunque los niveles de proteinuria de ambos grupos fueron similares al inicio y a los seis meses de iniciar el tratamiento con canakinumab, la proteinuria a los 12 meses fue significativamente menor en los pacientes con función renal preservada, en comparación con los pacientes con función renal deteriorada (2.462 ± 1.760 mg/día vs. 7.065 ± 3.035 mg/día, respectivamente, p = 0,02). Todos los pacientes con función renal preservada presentaron una disminución de la proteinuria superior al 50% a los 12 meses, en comparación con los valores iniciales, mientras que ninguno de los pacientes con función renal deteriorada presentó una disminución de la proteinuria de más del 50%. (AU)

Mean platelet volume in familial Mediterranean fever related AA amyloidosis and comparison with common primary glomerular diseases

Background/aim: Compared to healthy controls, mean platelet volume (MPV) is frequently higher in patients with Familial Mediterranean fever (FMF) but lower in AA amyloidosis patients. The reason for the difference in MPV levels in FMF patients with and without AA amyloidosis is unclear. The aim of the study was to determine whether low MPV is unique to AA amyloidosis or MPV is similarly low in all glomerular diseases as a result of proteinuria and/or renal dysfunction. Materials and methods: We compared pre-biopsy MPV levels of patients with AA amyloidosis secondary to FMF, to MPV levels of patients with membranous glomerulonephritis, focal segmental glomerulosclerosis (FSGS) and IgA nephropathy that all present with proteinuria and renal dysfunction. Results: 703 patients (411 male, 292 female) were included in the study. Mean age was 42.6  14.3 years. There were 124 patients with AA amyloidosis, 224 patients with IgA nephropathy, 188 patients with membranous glomerulonephritis, and 167 patients wit h FSGS. Patients with AA amyloidosis had lower MPV levels compared to patients without AA amyloidosis (7.9  1.2 fL vs. 8.2  0.9 fL respectively, p = 0.008). Patients with AA amyloidosis had significantly lower MPV compared to patients with each of the othe r diagnoses. Independent predictors of MPV were platelet count (ß = ­0.321, p < 0.001) and CRP (ß = ­ 0.134, p < 0.03). Conclusion: This study is the largest study of MPV in patients with biopsy proven AA amyloidosis and confirms previous studies reporting low MPV in AA amyloidosis. This study indicates that low MPV in AA amyloidosis cannot be explained with proteinuria and renal dysfunction.

Baseline renal functions predict the effect of canakinumab on regression of proteinuria in patients with familial Mediterranean fever.

INTRODUCTION AND OBJECTIVES: Canakinumab, an IL-1 blocking drug, decreases the frequency and severity of the attacks and decreases the proteinuria level in colchicine resistant/intolerant familial Mediterranean fever (FMF) patients. However, it is not known whether patients with impaired or preserved renal functions respond differently to IL-1 blocking therapies in terms of proteinuria reduction and progression of kidney dysfunction which was the aim of this study. MATERIALS AND METHODS: Adult FMF subjects with biopsy proven amyloidosis who had 24-h urine protein excretion>150mg/day before initiation of canakinumab were divided into two groups as patients with preserved renal function (GFR≥60mL/min) and patients with impaired renal function (GFR<60mL/min). The response in proteinuria and renal functions are compared between two groups in this cross-sectional study. RESULTS: A total of 18 patients (11 with preserved and 7 with impaired renal function) were included in this study. Although proteinuria levels of both groups were similar at the baseline and at six months after initiation of canakinumab, proteinuria at 12 months was significantly lower for patients with preserved renal function compared to patients with impaired renal function (2462±1760mg/day vs. 7065±3035mg/day respectively, p=0.02). All of the patients with preserved renal function had more than 50% decrease in proteinuria at 12 months compared to baseline values, while none of the patients with impaired renal function had more than 50% decrease in proteinuria. CONCLUSIONS: Canakinumab, an IL-1 blocking agent, is not effective in decreasing proteinuria in FMF patients with already impaired renal functions and should be started early in the course of disease to prevent renal impairment.

Baseline renal functions predict the effect of canakinumab on regression of proteinuria in patients with familial Mediterranean fever.

INTRODUCTION AND OBJECTIVES: Canakinumab, an IL-1 blocking drug, decreases the frequency and severity of the attacks and decreases the proteinuria level in colchicine resistant/intolerant familial Mediterranean fever (FMF) patients. However, it is not known whether patients with impaired or preserved renal functions respond differently to IL-1 blocking therapies in terms of proteinuria reduction and progression of kidney dysfunction which was the aim of this study. MATERIALS AND METHODS: Adult FMF subjects with biopsy proven amyloidosis who had 24-h urine protein excretion>150mg/day before initiation of canakinumab were divided into two groups as patients with preserved renal function (GFR≥60mL/min) and patients with impaired renal function (GFR<60mL/min). The response in proteinuria and renal functions are compared between two groups in this cross-sectional study. RESULTS: A total of 18 patients (11 with preserved and 7 with impaired renal function) were included in this study. Although proteinuria levels of both groups were similar at the baseline and at six months after initiation of canakinumab, proteinuria at 12 months was significantly lower for patients with preserved renal function compared to patients with impaired renal function (2462±1760mg/day vs. 7065±3035mg/day respectively, p=0.02). All of the patients with preserved renal function had more than 50% decrease in proteinuria at 12 months compared to baseline values, while none of the patients with impaired renal function had more than 50% decrease in proteinuria. CONCLUSIONS: Canakinumab, an IL-1 blocking agent, is not effective in decreasing proteinuria in FMF patients with already impaired renal functions and should be started early in the course of disease to prevent renal impairment.

Canakinumab treatment in renal transplant recipients with familial Mediterranean fever.

Colchicine is the first-line treatment for familial Mediterranean fever (FMF), preventing both inflammatory attacks as well as the development of amyloidosis in the majority of the patients. However approximately 5-10% of patients are colchicine resistant/intolerant. Side effects of colchicine are more prominent in renal transplant recipients due to interaction with immunosuppressive drugs. Anti-interleukin (IL)-1 drugs (anakinra, canakinumab and rilonacept) have emerged as the most promising drugs in the treatment of colchicine-resistant and/or intolerant FMF. There are no existing reports in the literature on canakinumab use in renal transplant recipients with FMF. We report here the efficacy and safety of canakinumab in three renal transplant recipients who achieved a complete clinical response with elimination of attacks and normalization of serum C-reactive protein (CRP) levels without significant side effects. This highlights the advantage of use of this drug in this setting, which has a better tolerability compared to anakinra.