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.

Is Chronic Kidney Disease Progression Influenced by the Type of Renin-Angiotensin-System Blocker Used?

INTRODUCTION: Angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin receptor blockers (ARBs) reduce proteinuria and slow renal disease progression more effectively than other therapies in patients with chronic kidney disease (CKD). However, differences regarding efficacy and safety between these therapies remain controversial. OBJECTIVES: Aim of this study was to analyze the different treatment effect of ACEI, ARB, and non-ACEI/ARB in CKD progression. The primary outcome was survival to end-stage renal disease (ESRD) and/or death and to ESRD censored by all-cause death, secondary outcomes were proteinuria reduction and hyperkalemia. METHODS: We analyzed data from 1,120 patients extracted from the National Renal Healthcare Program cohort, which included 17,238 CKD nondialysis subjects who were successively monitored between -September 1, 2004 and August 31, 2016. Inclusion criteria were at least a 1-year follow-up, 3 clinical visits, and no previous treatment with ACEI or ARB. From the baseline visit onward, patients continued with 3 different treatment schemes: no ACEI/ARB, started on ACEI or ARB, but while avoiding both treatments in combination. Chi2, t test, binary logistic regression, and multivariate regression models (Cox proportional Hazard model and competing risk Fine and Gray model were used for statistical analysis. RESULTS: Mean age and follow-up were 67.9 (± 15) and 3.8 (± 2) years, respectively. Estimated glomerular filtration rate averaged 42.1 ± 23 mL/min/1.73 m2 and 300 (27%) patients were diabetics. Progression to ESRD was significantly worse in the no ACEI/ARB group (hazard ratio [HR] 4.23, 95% CI 1.28-13.92) versus ACEI (reference group; p = 0.01). The analysis by competing-risks' regression showed significantly higher risk of ESRD in the no ACEI/ARB group (HR 3.63, 95% CI 1.34-9.85) versus ACEI (p = 0.01). There were no significant differences between ACEI and ARB groups (HR 1.31, 95% CI 0.37-4.66) regarding the risk of progression to ESRD. Survival was similar in all 3 groups (p = 0.051). Statistically significantly more patients experienced reductions in proteinuria/albuminuria in ACEI and ARB groups (together) versus no ACEI/ARB group (p = 0.016, OR 1.82, 95% CI 1.12-2.94). No difference in hyperkalemia frequency was found between them (p = 0.17). CONCLUSIONS: In patients with CKD, treatment with ACEI or ARB had a superior effect than no ACEI or ARB treatment on slowing kidney disease progression and on proteinuria reduction. Efficacy of ACEI and ARB was comparable.

Infective endocarditis in chronic haemodialysis: two treatment strategies.

BACKGROUND: Infective endocarditis (IE) is more frequent in patients on chronic haemodialysis (CHD) than in the general population and vascular access is the more frequent identified port of its entry. According to experimental and clinical studies the vascular access may also interfere with the treatment of IE. To improve the treatment of IE in CHD, patients were temporarily switched to peritoneal dialysis (PD) after the removal of the vascular access. In this preliminary report the outcome of IE in those CHD patients switched to PD is compared with the outcome in IE patients who remained on CHD. METHODS: All cases of IE that occurred during a 5 year period were retrospectively analysed. The Duke criteria for IE were used for diagnosis. All patients underwent transoesophageal echocardiography. All patients were treated with the same schedule of antibiotic treatment. The vascular access of a patient was removed when it was judged to be the source of infection. RESULTS: Twenty-one patients were studied. Twelve patients had been temporarily switched to PD after the diagnosis of IE and nine patients had remained on CHD treatment. There were not statistically significant differences between the two groups with respect to demographic data, comorbid diseases and the frequency of Staphylococcus aureus as the causative germ. In-hospital mortality was 8.3% in patients switched to PD and 55.5% in patients maintained on HD (P: 0.03). CONCLUSIONS: The data presented here suggest that the high mortality of IE in CHD patients may also be associated with the vascular access necessary for HD. If these results are confirmed by prospective studies with higher numbers of patients, PD could turn out to have a place in the treatment of IE in CHD patients.

Factores clínicos en la progresión de la insuficiencia renal crónica / Clinical factors concerning progression of chronic kidney insufficiency

Se estudia la influencia de distintos factores clínicos en la progresión (pr) de la insuficiencia renal crónica (IRC), revisando retrospectivamente la historia clínica de 65 pacientes (ptes) con IRC desde una creatininemia (PCr) inicial (i) de 3.2 + 1.01 mg por ciento hasta su ingreso en hemodiálisis (38 hombres, 27 mujeres; edad 50.6+15.6 años; seguimiento de 38.2+26.6 meses).Se definió la progresión por la pendiente -b de la regresión lineal (rg) de los valores de 1/PCr en relación al tiempo (t) y se controló la linearidad de esa relación por un método estadístico que detecta puntos de quiebre en la rg.La rg de 1/PCr-t describió adecuadamente la progresión en 47 ptes (grupo A) y mal en 18 (grupo B).En el grupo A la progresión no varió según el sexo, PCri, medio asistencial (público o privado), tipo de nefropatía o frecuencia de controles de policlínica.Hubo mayor progresión en los ptes con presión arterial (PA) media (PAM) de toda la evolución (PAMt) mayor de 120 mmHg respecto a los de PAMt inferior a 100 mmHg (p< 0.05) y correlación (r: 0.36) entre la PAM luego de los 5 mg por ciento de PCr y la progresión de la IRC, lo que se confirmó en análisis multivariado. Hubo más ptes hipertensos en el grupo A que en el grupo B (p< 0.05). Nuestro estudio confirmala relación directa entre hipertensión arterial y progresión de la IRC