Substitution of Oral for Intravenous Cyclophosphamide in Membranous Nephropathy.

Background: Optimal immunosuppressive treatment for membranous nephropathy is still a matter of controversy. Current recommendations include oral cyclophosphamide combined with steroids (modified Ponticelli regimen) as first-line treatment in patients who are high risk. However, concerns about the cumulative toxicity of oral cyclophosphamide persist. In the last 30 years, a protocol based on low-dose intravenous cyclophosphamide plus steroids has been used to treat membranous nephropathy in Uruguay. We aimed to assess the efficacy of this regimen to induce clinical remission in patients with membranous nephropathy. Methods: In this retrospective, observational cohort study, we analyzed the outcome of 55 patients with membranous nephropathy treated between 1990 and 2017 with a 6-month course of alternating steroids (months 1, 3, and 5) plus intravenous cyclophosphamide (single dose of 15 mg/kg on the first day of months 2, 4, and 6). Results: At 24 months, 39 (71%) patients achieved clinical response with complete remission observed in 23 patients (42%) and partial remission in 16 (29%). Median time to achieve partial and complete remission was 5.9 and 11.5 months, respectively. Absence of response was observed in 16 patients (29%), five of whom started chronic RRT after a median follow-up of 3.5 years. Clinical relapse occurred in nine of 33 (27%) patients at a median of 34 months after treatment discontinuation. Conclusions: Replacement of oral cyclophosphamide with a single intravenous pulse on months 2, 4, and 6 of the modified Ponticelli regimen can be an effective and safe alternative for treatment of membranous nephropathy. Podcast: This article contains a podcast at https://www.asn-online.org/media/podcast/K360/2020_09_24_KID0002802020.mp3.

Temporal trends in biopsy proven glomerular disease in Uruguay, 1990-2014.

Our aim is to describe variations in the incidence rates of glomerular disease diagnosed by renal biopsies performed in Uruguay over the last 25 years in relation to sex, age, clinical presentation and histological diagnosis. We analyzed all renal biopsies performed in Uruguay during the 25 years period and estimated incidence rates per million people per year (pmp/yr) for the population older than 14 years. Mann Kendall's trend analysis was used to assess incidence trends. In order to identify changes in trends, we compared annual incidence rates with the Joinpoint method. From 1990 to 2014, 3390 biopsies of native kidneys corresponding to glomerular disease were performed in patients older than 14 years. The average biopsy rate was 58 per pmp/yr. The glomerular disease incidence rate increased progressively over the period (p<0.05). Trends analysis over five-year periods demonstrated a progressive increase of IgA nephropathy (3.08 pmp/yr 1990-1994 to 12.53 pmp/yr 2010-2014 p<0.05), membranous nephropathy (2.38 pmp/yr 1990-1994 to 8.04 pmp/yr 2010-2014 p< 0.05) and lupus nephritis (4,23 pmp/yr 1990-1994 to 7,81 pmp/yr 2010-2014 p<0.05). There was a change in the trend of focal segmental glomerular sclerosis (FSGS) which increased until 1996 and decreased afterwards. The incidence rates of glomerular disease have doubled globally in the last quarter of a century in Uruguay, mainly related to the increase of IgA nephropathy, membranous nephropathy and lupus nephritis. There was a change in the slope of the incidence rate of FSGS.

Effectiveness and safety of a 6-month treatment with paricalcitol in patients on hemodialysis with secondary hyperparathyroidism.

Introduction: The mineral bone disorder, particularly secondary hyperparathyroidism, in chronic kidney disease (CKD) has a systemic impact affecting not only bone metabolism. Therefore its correction is important to prevent cardiovascular, inflammatory and immune diseases. Objective: To assess the effectiveness and safety of intravenous paricalcitol administered over a 6 month period for the treatment of secondary hyperparathyroidism (SHPT) in patients undergoing conventional hemodialysis, with close follow-up of treatment response. Methods: A phase 4 clinical trial was performed comparing clinical and laboratory data before and after 6 months of treatment. SHPT patients undergoing hemodialysis who were naïve to vitamin D metabolites or had failed to current therapy were included. Clinical and laboratory characteristics were analyzed. Efficacy analyses were based on intact parathyroid hormone (iPTH) levels and were performed using data from patients who completed 6 months of treatment. Results: Nineteen of the 26 patients enrolled completed 6 months of treatment. All patients exhibited reduced baseline iPTH levels (mean reduction, 371.8 pg/mL; 95% CI, 273.3-470.2 pg/mL]; 17 patients (89.5%) had reductions exceeding 30%. Twelve patients (63%) achieved therapeutic success (defined as iPTH serum levels 150-300 pg/mL), with a median time of 2 months from the beginning of treatment. All reported episodes of hypercalcemia (n = 2) and hyperphosphatemia (n = 34) were asymptomatic. No major therapy-related serious AEs were reported. Conclusion: Paricalcitol was safely administered and was associated with significant decreases in iPTH levels over the study period.

Introdução: A doença metabólica óssea, em particular o hiperparatireoidismo secundário, na doença renal crônica (DRC) tem um impacto sistêmico que afeta nem só o metabolismo ósseo. Por tanto, sua correção é importante para prevenir as doenças do sistema imunitário, inflamatório e cardiovascular. Objetivo: Avaliar a eficácia e a segurança do paricalcitol intravenoso administrado durante um período de 6 meses no tratamento do hiperparatireoidismo secundário (SHPT) em pacientes submetidos a hemodiálise convencional, com acompanhamento de perto da resposta do tratamento. Métodos: Realizou-se um ensaio clínico de fase 4 que comparava os dados clínicos com os dados do laboratório antes e depois dos 6 meses de tratamento. Incluíram-se os pacientes SHPT em hemodiálise sem experiência com os metabólitos da vitamina D ou que fracassaram com a terapia em uso. Analisaram-se as características clínicas e de laboratório. As análises de eficácia se basearam nos níveis do hormônio da paratireóide intacto (iPTH) e foram realizadas usando dados dos pacientes que completaram os 6 meses de tratamento. Resultados: Dezenove dos 26 pacientes registrados completaram os 6 meses de tratamento. Todos os pacientes mostraram níveis de referência iPTH reduzidos (redução média, 371,8 pg/mL; 95% CI, 273,3-470.2 pg/mL]; 17 pacientes (89,5%) tiveram reduções superiores a 30%. Doze pacientes (63%) conseguiram o sucesso terapêutico (definido como níveis de soros iPTH de 150-300 pg/mL), com um tempo médio de 2 meses a partir do início do tratamento. Todos os episódios de hipercalcemia (n = 2) e de hiperfosfatemia (n = 34) reportados foram assintomáticos. Não se informaram AEs graves importantes relacionados à terapia. Conclusão: O paricalcitol foi administrado de forma segura e se associou às reduções significativas nos níveis de iPTH durante o período do estudo.

Effectiveness and safety of a 6-month treatment with paricalcitol in patients on hemodialysis with secondary hyperparathyroidism / Eficácia e segurança do tratamento de 6 meses com paricalcitol em pacientes em hemodiálise com hiperparatiroidismo secundário

Abstract Introduction: The mineral bone disorder, particularly secondary hyperparathyroidism, in chronic kidney disease (CKD) has a systemic impact affecting not only bone metabolism. Therefore its correction is important to prevent cardiovascular, inflammatory and immune diseases. Objective To assess the effectiveness and safety of intravenous paricalcitol administered over a 6 month period for the treatment of secondary hyperparathyroidism (SHPT) in patients undergoing conventional hemodialysis, with close follow-up of treatment response. Methods: A phase 4 clinical trial was performed comparing clinical and laboratory data before and after 6 months of treatment. SHPT patients undergoing hemodialysis who were naïve to vitamin D metabolites or had failed to current therapy were included. Clinical and laboratory characteristics were analyzed. Efficacy analyses were based on intact parathyroid hormone (iPTH) levels and were performed using data from patients who completed 6 months of treatment. Results: Nineteen of the 26 patients enrolled completed 6 months of treatment. All patients exhibited reduced baseline iPTH levels (mean reduction, 371.8 pg/mL; 95% CI, 273.3-470.2 pg/mL]; 17 patients (89.5%) had reductions exceeding 30%. Twelve patients (63%) achieved therapeutic success (defined as iPTH serum levels 150-300 pg/mL), with a median time of 2 months from the beginning of treatment. All reported episodes of hypercalcemia (n = 2) and hyperphosphatemia (n = 34) were asymptomatic. No major therapy-related serious AEs were reported. Conclusion: Paricalcitol was safely administered and was associated with significant decreases in iPTH levels over the study period.

Resumo Introdução: A doença metabólica óssea, em particular o hiperparatireoidismo secundário, na doença renal crônica (DRC) tem um impacto sistêmico que afeta nem só o metabolismo ósseo. Por tanto, sua correção é importante para prevenir as doenças do sistema imunitário, inflamatório e cardiovascular. Objetivo: Avaliar a eficácia e a segurança do paricalcitol intravenoso administrado durante um período de 6 meses no tratamento do hiperparatireoidismo secundário (SHPT) em pacientes submetidos a hemodiálise convencional, com acompanhamento de perto da resposta do tratamento. Métodos: Realizou-se um ensaio clínico de fase 4 que comparava os dados clínicos com os dados do laboratório antes e depois dos 6 meses de tratamento. Incluíram-se os pacientes SHPT em hemodiálise sem experiência com os metabólitos da vitamina D ou que fracassaram com a terapia em uso. Analisaram-se as características clínicas e de laboratório. As análises de eficácia se basearam nos níveis do hormônio da paratireóide intacto (iPTH) e foram realizadas usando dados dos pacientes que completaram os 6 meses de tratamento. Resultados: Dezenove dos 26 pacientes registrados completaram os 6 meses de tratamento. Todos os pacientes mostraram níveis de referência iPTH reduzidos (redução média, 371,8 pg/mL; 95% CI, 273,3-470.2 pg/mL]; 17 pacientes (89,5%) tiveram reduções superiores a 30%. Doze pacientes (63%) conseguiram o sucesso terapêutico (definido como níveis de soros iPTH de 150-300 pg/mL), com um tempo médio de 2 meses a partir do início do tratamento. Todos os episódios de hipercalcemia (n = 2) e de hiperfosfatemia (n = 34) reportados foram assintomáticos. Não se informaram AEs graves importantes relacionados à terapia. Conclusão: O paricalcitol foi administrado de forma segura e se associou às reduções significativas nos níveis de iPTH durante o período do estudo.

Nefropatía C1q en un paciente de 17 años: caso clínico / C1q nephropathy: report ofone case

Clq nephropathy (Clq N) is an infrequent disease and only about 100 cases have been reponed. It is defined by a pattern of immunofluorescense (IF) with dominant or co-dominant complement Clq with electrondense deposits in the mesangium, without clinical or serological features of Lupus Nephritis. The most common histopathological findings of ClqN are focal segmental glomerulosclerosis and Minimal Change Disease. We repon a 17 year-old male patient with an isolated selective proteinuría found in a routine study. He had normal renal function and uriñe culture was negative. Serum lipids, liver enzymes an complement were all normal. Serum antinuclear and anti-DNA antibodies, antineutrophil cytoplasmic antibodies (ANCA), HIV, Hepatitis B and C serology, were negative. Renal and abdominal ultrasonography was normal. The histopathological study revealed segmental glomerular sderosis, modérate increase of mesangial matrix, Bowmann capsule adhesions and fucsinophil deposits in mesangium. The IF was positive (dominant) for Clq (+++) and IgA, IgG, IgM, C3++, all of them with a granular mesangial distribution. Ultrastructural findings were pedicelar effacement and paramesangial electrondense deposits. Tubular reticular inclusions (TRI) were not found. Remission of proteinuría was reached after 18 months of treatment with enalapril and losartan. The patient remains with normal renal function. Clinical findings, negative serology for Lupus, light microscopy IFwith dominant positivity for Clq, absence of TRI and paramesangial electrondense deposits in electron microscopy lead us to the diagnosis of ClqN. A poor response to steroid therapy was described in ClqN. Thus it was worthwhile to differentiate it from lupus nephritis, that is responsive to steroids.

[C1q nephropathy. Report of one case]. / Nefropatía C1q en un paciente de 17 años. Caso clínico.

Clq nephropathy (Clq N) is an infrequent disease and only about 100 cases have been reported. It is defined by a pattern of immunofluorescence (IF) with dominant or co-dominant complement Clq with electron-dense deposits in the mesangium, without clinical or serological features of Lupus Nephritis. The most common histopathological findings of ClqN are focal segmental glomerulosclerosis and Minimal Change Disease. We report a 17 year-old male patient with an isolated selective proteinuria found in a routine study. He had normal renal function and urine culture was negative. Serum lipids, liver enzymes an complement were all normal. Serum antinuclear and anti-DNA antibodies, antineutrophil cytoplasmic antibodies (ANCA), HIV, Hepatitis B and C serology, were negative. Renal and abdominal ultrasonography was normal. The histopathological study revealed segmental glomerular sclerosis, moderate increase of mesangial matrix, Bowmann capsule adhesions and fucsinophil deposits in mesangium. The IF was positive (dominant) for Clq (+++) and IgA, IgG, IgM, C3++, all of them with a granular mesangial distribution. Ultrastructural findings were pedicelar effacement and paramesangial electron-dense deposits. Tubular reticular inclusions (TRI) were not found. Remission of proteinuria was reached after 18 months of treatment with enalapril and losartan. The patient remains with normal renal function. Clinical findings, negative serology for Lupus, light microscopy IF with dominant positivity for Clq, absence of TRI and paramesangial electron-dense deposits in electron microscopy lead us to the diagnosis of ClqN. A poor response to steroid therapy was described in ClqN. Thus it was worthwhile to differentiate it from lupus nephritis, that is responsive to steroids.

The renal osteodystrophy pattern in Brazil and Uruguay: an overview.

BACKGROUND: The prevalence of the types of renal osteodystrophy (ROD) has changed in the last two decades. This study evaluates the prevalence and determining factors of the types of ROD in two countries in South America. METHODS: Symptomatic patients who underwent bone biopsies for diagnostic purposes (1985 through 2001) were included in the study. In Brazil, a total of 2340 patients were reviewed, 93.1% on hemodialysis (HD), and 6.9% on continuous ambulatory peritoneal dialysis (CAPD). In Uruguay, 167 patients on hemodialysis were included. Uncalcified bone samples were analyzed in order to diagnose the different types of ROD. RESULTS: Comparing the 1980s to the 1990s, the prevalence of Brazilian patients with hyperparathyroid bone disease (HP) increased from 32.3% to 44.0%, while Al overload decreased from 61.3% to 42.4%. A logistic regression analysis showed that the main factors associated with HP included female gender, age of less than 40 years, black patients, longer time on dialysis, and absence of Al overload. In Uruguay, HP also increased over time from 31.8% to 70.5% (P < 0.05), while Al overload decreased from 42% to 27% (P < 0.05). CONCLUSION: A better control of Al overload may lead to a change in histologic pattern, as evidenced by the increasing prevalence of HP.