Final Efficacy Results of Neratinib in HER2-positive Hormone Receptor-positive Early-stage Breast Cancer From the Phase III ExteNET Trial.

BACKGROUND: The ExteNET trial demonstrated improved invasive disease-free survival (iDFS) with neratinib, an irreversible pan-HER tyrosine kinase inhibitor, versus placebo in patients with human epidermal growth factor receptor 2-positive (HER2+)/hormone receptor-positive (HR+) early-stage breast cancer (eBC). PATIENTS AND METHODS: ExteNET was a multicenter, randomized, double-blind, phase III trial of 2840 patients with HER2+ eBC after neoadjuvant/adjuvant trastuzumab-based therapy. Patients were stratified by HR status and randomly assigned 1-year oral neratinib 240 mg/day or placebo. The primary endpoint was iDFS. Descriptive analyses were performed in patients with HR+ eBC who initiated treatment ≤ 1 year (HR+/≤ 1-year) and > 1 year (HR+/> 1-year) post-trastuzumab. RESULTS: HR+/≤ 1-year and HR+/> 1-year populations comprised 1334 (neratinib, n = 670; placebo, n = 664) and 297 (neratinib, n = 146; placebo, n = 151) patients, respectively. Absolute iDFS benefits at 5 years were 5.1% in HR+/≤ 1-year (hazard ratio, 0.58; 95% confidence interval [CI], 0.41-0.82) and 1.3% in HR+/>1-year (hazard ratio, 0.74; 95% CI, 0.29-1.84). In HR+/≤ 1-year, neratinib was associated with a numerical improvement in overall survival (OS) at 8 years (absolute benefit, 2.1%; hazard ratio, 0.79; 95% CI, 0.55-1.13). Of 354 patients in the HR+/≤ 1-year group who received neoadjuvant therapy, 295 had residual disease, and results showed absolute benefits of 7.4% at 5-year iDFS (hazard ratio, 0.60; 95% CI, 0.33-1.07) and 9.1% at 8-year OS (hazard ratio, 0.47; 95% CI, 0.23-0.92). There were fewer central nervous system events with neratinib. Adverse events were similar to those previously reported. CONCLUSION: Neratinib significantly improved iDFS in the HER2+/HR+/≤ 1-year population, and a similar trend was observed in patients with residual disease following neoadjuvant treatment. Numerical improvements in central nervous system events and OS were consistent with iDFS benefits and suggest long-term benefit for neratinib in this population.

Functional PTGS2 polymorphism-based models as novel predictive markers in metastatic renal cell carcinoma patients receiving first-line sunitinib.

Sunitinib is the currently standard treatment for metastatic renal cell carcinoma (mRCC). Multiple candidate predictive biomarkers for sunitinib response have been evaluated but none of them has been implemented in the clinic yet. The aim of this study was to analyze single nucleotide polymorphisms (SNPs) in genes linked to mode of action of sunitinib and immune response as biomarkers for mRCC. This is a multicenter, prospective and observational study involving 20 hospitals. Seventy-five mRCC patients treated with sunitinib as first line were used to assess the impact of 63 SNPs in 31 candidate genes on clinical outcome. rs2243250 (IL4) and rs5275 (PTGS2) were found to be significantly associated with shorter cancer-specific survival (CSS). Moreover, allele C (rs5275) was associated with higher PTGS2 expression level confirming its functional role. Combination of rs5275 and rs7651265 or rs2243250 for progression free survival (PFS) or CSS, respectively, was a more valuable predictive biomarker remaining significant after correction for multiple testing. It is the first time that association of rs5275 with survival in mRCC patients is described. Two-SNP models containing this functional variant may serve as more predictive biomarkers for sunitinib and could suppose a clinically relevant tool to improve the mRCC patient management.

Residual urinary output in high body mass index individuals on chronic hemodialysis: A disregarded life vest?

AIM: To assess residual diuresis and diverse variables according to body mass index (BMI). METHODS: Cross-sectional study (n = 57), with 3 groups. Group A: BMI < 25, n = 22; Group B: BMI 25-30, n = 15; Group C: BMI > 30, n = 20. Diuresis, hematocrit, albumin, C-reactive protein, Malnutrition inflammatory score, Pro-BNP, Troponin T, leptin and insulin levels are expressed as median and ranges (r). RESULTS: Albumin (g/dL): GA vs GC, 3.70 (r2.20-4.90) vs 3.85 (r3.40-4.90), P = 0.02. Diuresis (mL/d): GA 690 (r0-1780); GB 660 (r60-1800); GC 840 (r40-2840). Diuresis GA vs GC, P = 0.01. Leptin (ng/mL): GA vs GC, 3.81 (r0.78-69.60) vs GC, 32.80 (r0.78-124.50), P < 0.001. Insulin (µU/mL): GA vs GB, 7 (r2-44) vs 11.50 (r4-38), P = 0.02; GA vs GC, 7 (r2-44) vs 19.5 (r5-155), P = 0.0001. Troponin T and Pro-BNP levels were not different. Significant correlations: GC, Insulin-UF: ρ = 0.53; P = 0.03; TroponinT-diuresis: ρ = -0.48, P < 0.05; Pro-BNP-diuresis: ρ = -0.39, P < 0.01; Troponin T-ProBNP: ρ = 0.77, P < 0.0001; albumin-Troponin T: ρ = -0.66, P < 0.0001; albumin-ProBNP: ρ = -0.44, P < 0.05. CONCLUSION: High BMI associated positively with higher diuresis and albuminemia, and negatively with TropT and Pro-BNP. High BMI-associated better survival may be explained by better urinary output, lowering cardiovascular stress.

Comparación ensayos de parathormona de segunda y tercera generación y su utilidad en hemodializados crónicos / Comparison of third and second generation parathyroid hormone assays and their use in chronic hemodialysis patiens

Introducción: El objetivo del trabajo es comparar ensayos de PTH de 2da y 3ra generación en pacientes con función renal normal y en hemodializados crónicos y sus implicancias en el tratamiento de esta última población. Métodos: Se estudiaron 60 pacientes hemodializados crónicos y 40 con función renal normal a quienes se les midió PTH por ambos ensayos. Resultados: En la población con función renal normal la mediana de PTH fue de 51.8 y de 45.6 pg/ml con el ensayo de 2da y 3ra generación respectivamente. En hemodializados crónicos la mediana de PTH fue de 193.9 y de 137.1 pg/ml con los ensayos de 2da y 3ra generación respectivamente. La diferencia entre los ensayos fue de 11.3% y 29.3% en la población con función renal y hemodializados respectivamente. El ensayo de 3ra generación produjo un corrimiento en la cantidad de pacientes que caen en los distintos rangos de PTH según las guías KDIGO, para un valor menor de 2 veces el límite superior de referencia: cambia de 20 a 25 pacientes, entre 2 y 9 veces: cambia de 31 a 32 pacientes y mayor de 9 veces: cambia de 9 a 3 pacientes. Conclusiones: Al aumentar la concentración de PTH aumentan las diferencias entre ambos ensayos, por lo que no se pueden utilizar indistintamente en una población de hemodializados crónicos.Con los ensayos de 3ra generación 11 pacientes (18.3%) modificaron su clasificación de acuerdo a las guías KDIGO lo que implicaría un cambio en el tratamiento.

Introduction: This work's objective is to compare third and second generation assays in patients with normal kidney function and in chronic hemodialysis patients, and the implications on the latter. Methods: 60 chronic hemodialysis patients and 40 patients with normal kidney function were studied and their PTH levels were measured for both assays. Results: In patients population with normal kidney function the average on PTH was 51.8 and 45.6 pg/ml with second and third generation assays respectively. In chronic hemodialysis patients the average PTH was 193.9 and 137.1 pg/ml with second and third generation assays respectively. The difference between assays was 11.3% and 29.3% in patients with normal kidney function and in hemodialysis patients respectively. Third generation assay caused a variation in the amount of patients that fall over several PTH ranges according to KDIGO guidelines, for a lesser value of 2 times the reference upper limit: it changes from 20 to 25 patients, between 2 and 9 times: it changes from 31 to 32 patients, and more than 9 times: it changes from 9 to 3 patients. Conclusions: When PTH concentration increases the difference between both assays also increases, for this reason we cannot use them indiscriminately in a chronic hemodialysis patient population. With third generation assays 11 patients (18.3%) changed their classification according to KDIGO guidelines, which will result in a change of treatment.

Pro-calcitonin and inflammation in chronic hemodialysis.

UNLABELLED: Procalcitonin (PCT) has emerged as a marker of infection, a frequent complication in hemodialysis (HD). We analyzed PCT levels in chronic non-acutely infected HD subjects, assessed its correlation with inflammatory and nutritional markers and propose a PCT reference value for non-infected HD patients. In an observational cross-sectional study, 48 chronic HD patients and 36 controls were analyzed. VARIABLES: age, gender, time on HD; diabetes; vascular access, PCT, C-reactive protein (CRP), albumin, malnutrition inflammatory score (MIS), hematocrit, leukocyte count, and body mass index (BMI). Subsequently, control (G1, n = 36, 43%) vs. non-infected patients (G2, n = 48, 57%) groups were compared. In control subjects (G1), age: 54.3 ± 13.7 years, range (r): 30-81; males: 19 (53%); median PCT 0.034 ng/ml (r: 0.02-0.08); median CRP 0.80 mg/ dl (r: 0.36-3.9); p95 PCT level: 0.063 ng/ml. In G2, age: 60.2 ± 15.2 years; males 32 (67%), time on HD: 27.0 ± 24.4; diabetics: 19 (32%); median PCT: 0.26 ng/ml (r: 0.09-0.82); CRP: 1.1 mg/dl (r: 0.5-6.2); p95 PCT level: 0.8 ng/ml. In control subjects, PCT and CRP were significantly lower than in G2: PCT: 0.034 vs. 0.26 ng/ml, p = 0.0001; CRP: 0.8 vs. 1.1 mg/dl, p = 0.0004. PCT-CRP correlation in G2: p = 0.287, p = 0.048. PCT and CRP concentrations are elevated in chronic non-acutely infected HD subjects, independently of infection, diabetes and vascular access. A p95 PCT level of 0.8 ng/ml may be considered as the upper normal reference value in non-acutely infected HD subjects. The PCT cut-off level in HD is yet to be determined in HD.

Pro-calcitonin and inflammation in chronic hemodialysis / Pro-calcitonina e inflamación en hemodiálisis crónica

Procalcitonin (PCT) has emerged as a marker of infection, a frequent complication in hemodialysis (HD). We analyzed PCT levels in chronic non-acutely infected HD subjects, assessed its correlation with inflammatory and nutritional markers and propose a PCT reference value for non-infected HD patients.In an observational cross-sectional study, 48 chronic HD patients and 36 controls were analyzed. Variables: age, gender, time on HD; diabetes; vascular access, PCT, C-reactive protein (CRP), albumin, malnutrition inflammatory score (MIS), hematocrit, leukocyte count, and body mass index (BMI). Subsequently, control (G1, n = 36, 43%) vs. non-infected patients (G2, n = 48, 57%) groups were compared. In control subjects (G1), age: 54.3 ± 13.7 years, range (r): 30-81; males: 19 (53%); median PCT 0.034 ng/ml (r: 0.02-0.08); median CRP 0.80 mg/dl (r: 0.36-3.9); p95 PCT level: 0.063 ng/ml. In G2, age: 60.2 ± 15.2 years; males 32 (67%), time on HD: 27.0 ± 24.4; diabetics: 19 (32%); median PCT: 0.26 ng/ml (r: 0.09-0.82); CRP: 1.1 mg/dl (r: 0.5-6.2); p95 PCT level: 0.8 ng/ml. In control subjects, PCT and CRP were significantly lower than in G2: PCT: 0.034 vs. 0.26 ng/ml, p = 0.0001; CRP: 0.8 vs. 1.1 mg/dl, p = 0.0004. PCT-CRP correlation in G2: ρ = 0.287, p = 0.048. PCT and CRP concentrations are elevated in chronic non-acutely infected HD subjects, independently of infection, diabetes and vascular access. A p95 PCT level of 0.8 ng/ml may be considered as the upper normal reference value in non-acutely infected HD subjects. The PCT cut-off level in HD is yet to be determined in HD.

La procalcitonina (PCT) puede ser un marcador de infección en la hemodiálisis (HD). Analizamos los niveles de PCT en sujetos sin infección aguda en HD crónica, su correlación con marcadores inflamatorios y nutricionales y, de acuerdo a ello, proponemos niveles de referencia de PCT. En un estudio observacional transversal se estudiaron 48 pacientes en HD y 36 controles. Variables: edad; sexo, tiempo en HD; diabetes; acceso vascular, PCT, proteína C-reactiva (PCR), albúmina, score de malnutrición-inflamación, hematocrito, recuento leucocitario, e índice de masa muscular (IMC). En los controles se determinaron PCT y PCR. Se comparó grupo control (G1, n = 36, 43%) vs. pacientes (G2, n = 48, 57%). G1: edad, 54.3 ± 13.7, rango (r): 30-81 años; hombres: 19 (53%); PCT mediana: 0.034 ng/ml (r: 0.020-0.080); PCR mediana: 0.8 mg/dl (r: 0.36-3.9); el nivel p95 de PCT: 0.063 ng/ml. En el G2, edad media 60.2 ± 15.2 años, hombres: 32 (66%), tiempo en HD: 27.0 2 4.4; diabéticos: 19 (32%); PCT: 0.26 ng/ml (r: 0.09-0.82); PCR: 1.1 mg/dl (r: 0.5-6.2); p95 PCT: 0.8 ng/ml. En G1 los niveles de PCT y PCR fueron significativamente más bajos que en G2: PCT: 0.034 vs. 0.26 ng/ml, p = 0.0001; PCR: 0.8 vs 1.1 mg/dl, p = 0.0004. Correlación PCT- PCR en G2: ρ = 0.287, p = 0.048. La PCT y la PCR están elevadas en HD crónica independientemente de infección, diabetes y acceso vascular. Se propone p95 de PCT de 0.8 ng/ml como límite superior del intervalo de referencia en sujetos sin infección aguda en HD. El valor de PCT en HD está por determinarse.

Proteinuria and its relation to diverse biomarkers and body mass index in chronic hemodialysis.

BACKGROUND: Certain adipokines exert direct effects on proteinuria, a cardiovascular risk factor ignored in hemodialysis. We measured different adipokines according to body mass index (BMI) in relation to proteinuria. METHODS: Patients numbered 57: group A (GA), BMI<25, n = 22; GB, BMI 25-30, n = 15; and GC, BMI > 30, n = 20. There were no statistical differences in age, sex, time on dialysis, cause of renal failure, diabetes, hypertension, C-reactive protein, or nutritional status. Measures were taken of 24-hour diuresis and proteinuria, ultrafltration, albumin, pro-brain natriuretic peptide (Pro-BNP), insulin, adiponectin, leptin, and ghrelin. RESULTS: Proteinuria was signifcantly higher in GC versus (vs) GA (1.5 g/day, range 0.30-14 vs 0.72 g/day, range 0.1-2.7; P < 0.01) and correlated signifcantly with leptin levels (ρ = 0.47, P < 0.05). In GA, elevated levels of Pro-BNP, adiponectin, and ghrelin were associated with lower degrees of proteinuria. Signifcant correlations were found between adiponectin and leptin (ρ = -0.54, P = 0.03), and adiponectin and Pro-BNP (ρ = 0.59, P = 0.02). Though not signifcant, there were more diabetics in GC (GA four, GB three, GC ten). As BMI increased in GB and GC, Pro-BNP, adiponectin, and ghrelin levels decreased signifcantly, while proteinuria, insulin, and homeostasis model assessment of insulin resistance increased. Leptin levels were signifcantly elevated in GC vs GA and GB. In GC, ghrelin correlated signifcantly with Pro-BNP (ρ = 0.51, P = 0.03), while leptin correlation with Pro-BNP was inverse and signifcant in GA (ρ = -0.74, P < 0.001) and inverse and nonsignifcant in GB and GC. CONCLUSION: In patients with BMI < 25, higher adiponectin, ghrelin, and Pro-BNP levels were associated with lower proteinuria and leptinemia. In obesity, hyperleptinemia and hyperinsulinemia associated with higher proteinuria; whether decreased adiponectin-ghrelin-ProBNP and/or elevated leptin-insulin levels aggravate proteinuria remains to be determined.

Proteinuria: an ignored marker of inflammation and cardiovascular disease in chronic hemodialysis.

BACKGROUND: Cardiovascular disease is the leading cause of morbidity and mortality in hemodialysis (HD) patients, the main etiologies being diabetes and hypertension. Cardiac and inflammatory biomarkers are usually employed to assess risk or damage, or during follow-up. Proteinuria is considered a strong predictor of morbidity, a cause of inflammation, oxidative stress, hemodynamic alteration, and progression of chronic kidney disease. However, proteinuria is rarely considered in the clinical assessment of HD patients. METHODS: This was a concurrent, cohort-observational, cross-sectional study in which 52 chronic HD subjects were divided into three groups according to the degree of proteinuria: Group (G) A: <1 g/day, n = 25; GB: 1-3 g/day, n = 13; GC: >3 g/day, n = 14. Baseline hemoglobin, albuminemia, cholesterol, body mass index, Malnutrition-Inflammatory Score, pro-B-type natriuretic peptide, troponin T, C-reactive protein (CRP), and ultrafiltration rates were analyzed. RESULTS: There was no difference between groups in terms of baseline age, gender, hypertension, cause of renal failure, hemoglobin, cholesterol, albumin, CRP levels, cardiac biomarkers, adiponectin, body mass index, or Malnutrition-Inflammatory Score. Time on HD: GA, 34.56 ± 23.3 (range [r]: 6-88); GB, 25.15 ± 19.40 (r: 6-58); GC, 18.21 ± 9.58 (r: 6-74) months; P = 0.048. Proteinuria: GA, 0.33 ± 0.30 (r: 0.0-0.88); GB, 1.66 ± 0.54 (r: 1.03-2.75); GC, 7.18 ± 2.80 (r: 3.04-21.5) g/day; P < 0.001. Mean ultrafiltration rates were significantly different: GA, 2.80 ± 0.73; GB: 1.85 ± 0.96 liters/session; P = 0.003. Fourteen diabetic patients were identified (27%): GA, 3 (12%); GB, 3 (23%); GC, 8 (57%); P = 0.009. A positive and significant correlation was observed between diabetes and proteinuria >3 g/day: rho 0.438, P = 0.027. Although troponin T, pro-B-type natriuretic peptide, adiponectin, and CRP were not different among groups, the positive correlation between troponin T and CRP elevated significantly as proteinuria increased: GA, rho 377, P = 0.063; GB, rho 663, P = 0.013; GC, rho 687, P = 0.007. CONCLUSION: In chronic HD, nephrotic-range proteinuria was significantly higher in diabetic nephropathy patients versus other causes. This was associated with inflammation and cardiac stress and was independent of fluid removal. Proteinuria >3 g/day was associated with shorter time on HD. Whether severe proteinuria is associated with shorter survival in HD, independent of diabetes, is to be determined. Proteinuria should be considered in the assessment of cardiovascular and inflammatory states in HD patients.

Creatinine- vs. cystatin C-based equations compared with 99mTcDTPA scintigraphy to assess glomerular filtration rate in chronic kidney disease.

BACKGROUND: In chronic kidney disease (CKD), accurate estimation of the glomerular filtration rate (GFR) is mandatory. Gold standard methods for its estimation are expensive and time-consuming. We compared creatinine- versus cystatin C-based equations to measure GFR, employing (99m)Tc-DTPA scintigraphy as the gold standard. METHODS: This was a prospective cross-sectional observational study including 300 subjects. CKD was defined according to K/DOQI guidelines, and patients were separated into groups: stage 1 (G1), n=26; stage 2 (G2), n=52; stage 3 (G3), n=90; stage 4 (G4), n=37; stage 5 (G5), n=60; and control group, n=35. Creatinine-based estimates were from 24-hour creatinine clearance using the Walser formula, Cockcroft-Gault, MDRD-4 and CKD-EPI; cystatin C equations used were Larsson, Larsson modified equation, Grubb and Hoek. RESULTS: Age and body mass index were different among groups; proteinuria, hypertension, diabetes and primary glomerulopathies significantly increased as CKD worsened. In the global assessment, CKD-EPI and Hoek gave the highest correlations with (99m)Tc-DTPA: rho=0.826, p<0.001 and rho=0.704, p<0.001, respectively. Most significant linear regressions obtained: CKD-EPI vs. (99m)Tc-DTPA, Hoek vs. (99m)Tc-DTPA and CKD-EPI vs. Hoek. However, important differences emerged when each group was analyzed separately. Best significant correlations obtained with (99m)Tc-DTPA: control group, creatinine clearance rho=0.421, p=0.012; G1, Crockoft-Gault rho=0.588, p=0.003; G2, CKD-EPI rho=0.462, p<0.05; G3, CKD-EPI rho=0.508, p<0.001; G4, Hoek rho=0.618, p<0.001; G5, CKD-EPI rho=0.604, p<0.001. CONCLUSIONS: At GFR <60 ml/min, CKD-EPI and Hoek equations appeared to best correlate with (99m)TcDTPA. In controls and at early stages of CKD, creatinine-based equations correlated better with (99m)Tc-DTPA, with CKD-EPI being the one with the best degree of agreement.

In hemodialysis, adiponectin, and pro-brain natriuretic peptide levels may be subjected to variations in body mass index.

Adiponectin exerts cardiovascular protective actions, although some studies have shown the opposite. In hemodialysis, obese subjects display lower mortality rates despite hypoadiponectinemia, while higher adiponectin concentrations correlate with an elevated cardiovascular risk in nonobese subjects. The aim of the study is to suggest that adiponectin level variations are associated with differences in the body mass index (BMI). The interplay between adiponectin and pro-brain natriuretic peptide (Pro-BNP) levels may vary according to body fat mass. Fifty-two chronic hemodialysis patients were divided into three groups. Group A, BMI<25 (n=20); Group B, BMI 25 to 30 (n=21), and Group C, BMI>30 (n=11). Diabetics: Group A 10%; Group B 6 29%; Group C 55%, P=0.027. Determinations: Adiponectin, Pro-BNP, insulin, insulin resistance (HOMA), troponin T, nutritional status, ultrafiltration rates, C-reactive protein (CRP), vascular accesses, and echocardiography. Group A: adiponectinemia positively and significantly correlated with Pro-BNP, CRP, and troponin T. As BMI increased, adiponectin, Pro-BNP, and malnutrition significantly decreased, while insulin, HOMA, and ultrafiltration rates significantly increased. Cardiac restriction was significantly higher in obese patients. In all groups, Pro-BNP and troponin T displayed a strong positive correlation. In low-BMI subjects, high Pro-BNP and adiponectin, low myocardial restriction, and worse nutritional status were prevalent. In obesity, hypoadiponectinemia stimulates cardiac remodeling, cardiac hypertrophy, and decreased stretching, rendering Pro-BNP levels low despite high ultrafiltration rates. Thus, adiponectin correlates inversely with BMI, probably playing different cardiovascular roles as BMI changes.

Elevated pro-brain natriuretic peptide, troponin T and malnutrition inflammatory score in chronic hemodialysis patients with overt cardiovascular disease.

BACKGROUND: We assessed the relationship between pro-brain natriuretic peptide (pro-BNP), troponin T (TropT) and nutritional status. METHODS: A total of 48 chronic hemodialysis patients were grouped according to the presence [group A (GA); n = 24] or not [group B (GB)] of cardiovascular disease. RESULTS: Compared to GB subjects, GA subjects were older, had been on hemodialysis for a longer period and had higher prevalences of vascular grafts, hypertension and elevated C-reactive protein (CRP) [GA vs. GB: 1.1 (range 0.1-32.9) vs. 0.4 (0-28.1) mg/dl; p = 0.028], malnutrition inflammatory score (MIS) (GA vs. GB: 7.50 vs. 4.00; p = 0.001), pro-BNP [GA vs. GB: 6,760 (601-103,200) vs. 686 (75-83,700) pg/ml; p < 0.001] and TropT [GA vs. GB: 0.3650 (0.011-0.199) vs. 0.010 (0.0-0.290) ng/ml; p = 0.002]. Pro-BNP correlated with TropT (rho 0.539; p < 0.001), MIS (rho 0.502; p < 0.0001), homocysteine (rho 0.321; p = 0.13) and CRP (rho 0.511; p < 0.0001). Pro-BNP levels were lower in GB patients as the body mass index increased; the opposite occurred in GA. CONCLUSIONS: Patients with cardiovascular disease had elevated pro-BNP and TropT levels. In patients without cardiovascular disease, malnutrition and inflammation were associated with vascular prostheses, while pro-BNP was lower in obese patients.

Dual renin-angiotensin system blockade plus oral methylprednisone for the treatment of proteinuria in IgA nephropathy.

Renin-angiotensin system inhibition is a widely accepted approach to initially deal with proteinuria in IgA nephropathy, while the role of immunosuppressants remains controversial in many instances. A prospective, uncontrolled, open-label trial was undertaken in patients with biopsy-proven IgA nephropathy with proteinuria > 0.5 g/day and normal renal function to assess the efficacy of a combination treatment of angiotensin converting enzyme inhibitors plus angiotensin receptor blockers enalapril valsartan coupled with methylprednisone to decrease proteinuria to levels below 0.5 g/day. Twenty patients were included: Age 37.45 +/- 13.26 years (50% male); 7 patients (35%) were hypertensive; proteinuria 2.2 +/- 1.86 g/day; serum creatinine 1.07 +/- 0.29 mg/dl; mean follow-up 60.10 +/- 31.47 months. IgA nephropathy was subclassified according to Haas criteria. Twelve patients (60%) were class II; seven (35%) were class III and one (5%) class V. All patients received dual renin-angiotensin system blockade as tolerated. Oral methylprednisone was started at 0.5 mg/kg/day for the initial 8 weeks and subsequently tapered bi-weekly until the maintenance dose of 4 mg was reached. Oral steroids were discontinued after 24 weeks (6 months) of therapy but renin-angiotensin inhibition remained unchanged. At 10 weeks of therapy proteinuria decreased to 0.15 +/- 0.07 g/day (P < 0.001) while serum creatinine did not vary: 1.07 +/- 0.28 mg/dl (P = ns). After a mean follow-up of 42.36 +/- 21.56 months urinary protein excretion (0.12 +/- 0.06 g/day) and renal function (serum creatinine 1.06 +/- 0.27 mg/dl) remained stable. No major side effects were reported during the study. Renin-angiotensin blockade plus oral steroids proved useful to significantly decrease proteinuria to < 0.5 g/day in patients with IgA nephropathy without changes in renal function.

Dual renin-angiotensin system blockade plus oral methylprednisone for the treatment of proteinuria in IgA nephropathy / Doble bloqueo del sistema renina-angiotensina más metilprednisona oral para el tratamiento de la proteinuria en la nefropatía por IgA

Renin-angiotensin system inhibition is a widely accepted approach to initially deal with proteinuria in IgA nephropathy, while the role of immunosuppressants remains controversial in many instances. A prospective, uncontrolled, open-label trial was undertaken in patients with biopsy-proven IgA nephropathy with proteinuria more than 0.5 g/day and normal renal function to assess the efficacy of a combination treatment of angiotensin converting enzyme inhibitors plus angiotensin receptor blockers enalapril valsartan coupled with methylprednisone to decrease proteinuria to levels below 0.5 g/day. Twenty patients were included: Age 37.45 more or less 13.26 years (50% male); 7 patients (35%) were hypertensive; proteinuria 2.2 more or less 1.86 g/day; serum creatinine 1.07 more or less 0.29 mg/dl; mean follow-up 60.10 more or less 31.47 months. IgA nephropathy was subclassified according to Haas criteria. Twelve patients (60%) were class II; seven (35%) were class III and one (5%) class V. All patients received dual reninangiotensin system blockade as tolerated. Oral methylprednisone was started at 0.5 mg/kg/day for the initial 8 weeks and subsequently tapered bi-weekly until the maintenance dose of 4 mg was reached. Oral steroids were discontinued after 24 weeks (6 months) of therapy but renin-angiotensin inhibition remained unchanged. At 10 weeks of therapy proteinuria decreased to 0.15 more or less 0.07 g/day (P less than 0.001) while serum creatinine did not vary: 1.07 ± 0.28 mg/dl (P=ns). After a mean follow-up of 42.36 more or less 21.56 months urinary protein excretion (0.12 more or less 0.06 g/day) and renal function (serum creatinine 1.06 more or less 0.27 mg/dl) remained stable. No major side effects were reported during the study. Renin-angiotensin blockade plus oral steroids proved useful to significantly decrease proteinuria to less than 0.5 g/day in patients with IgA nephropathy without changes in renal function.

El doble bloqueo del sistema renina-angiotensina con inhibidores de la enzima convertidora de angiotensina junto a bloqueadores del receptor tipo I de angiotensina II es aceptado como tratamiento en la proteinuria de la nefropatía por IgA, ya que el rol de los inmunosupresores continúa siendo controvertido. Estudio prospectivo, no controlado, abierto para pacientes con nefropatía por IgA con proteinurias major que 0.5 g/día y creatininas séricas menor que 1.4 mg/dl, para evaluar la eficacia de tratamiento de enalapril más valsartán asociado a metilprednisona vía oral para disminuir las proteinurias a menor que 0.5 g/día. Fueron incluidos 20 pacientes: Edad: 37.45 más o menos 13.3 años (50% hombres); 7 pacientes (35%) eran hipertensos; proteinuria inicial 2.2 más o menos 1.86 g/día; creatinina inicial 1.07 más o menos 0.29 mg/dl; seguimiento promedio: 60.10 más o menos 31.47 meses (5 más o menos 2.62 años). La nefropatía por IgA fue subclasificada según Haas: 12 pacientes (60%) clase II; 7 (35%) clase III y 1 (5%) clase V. Todos recibieron enalapril más valsartán según tolerancia más metilprednisona vía oral en dosis de 0.5 mg/kg/día durante las primeras 8 semanas y subsecuentemente se redujo cada dos semanas hasta llegar a 4 mg. Se discontinuaron los esteroides luego de 24 semanas (6 meses). La inhibición del sistema renina angiotensina prosiguió indefinidamente. A las 10 semanas la proteinuria disminuyó de 2.2 más o menos 1.86 g/día a 0.15 más o menos 0.7 g/día (p menor que 0.001); la creatinina no varió significativamente (1.07 más o menos 0.29 mg/dl vs. 1.07 más o menos 0.28 mg/dl) (P=ns). Luego de 10 semanas y con un seguimiento de 42.36 más o menos 21.56 meses la proteinuria (0.12 más o menos 0.006 g/día) y la función renal (creatinina 1.06 más o menos 0.27mg/dl) permanecieron estables. No se informaron efectos adversos durante el estudio. El doble bloqueo del sistema renina angiotensina más bajas dosis de metilprednisona resultó útil para reducir...