Vascular access type and mortality in elderly incident hemodialysis patients / Tipo de acceso vascular y mortalidad en pacientes ancianos en programa de hemodiálisis

Introduction: The ideal vascular access type for elderly hemodialysis (HD) patients remains debatable. The aim of this study was to analyze the association between patterns of vascular access use within the first year of HD and mortality in elderly patients. Methods: Single-center retrospective study of 99 incident HD patients aged≥80 years from January 2010 to May 2021. Patients were categorized according to their patterns of vascular access use within the first year of HD: central venous catheter (CVC) only, CVC to arteriovenous fistula (AVF), AVF to CVC, and AVF only. Baseline clinical data were compared among groups. Survival outcomes were analyzed using Kaplan–Meier survival curves and Cox's proportional hazards model. Results: When compared with CVC to AVF, mortality risk was significantly higher among CVC only patients and similar to AVF only group [HR 0.93 (95% CI 0.32–2.51)]. Ischemic heart disease [HR 1.74 (95% CI 1.02–2.96)], lower levels of albumin [HR 2.16 (95% CI 1.28–3.64)] and hemoglobin [HR 4.10(95% CI 1.69–9.92)], and higher levels of c-reactive protein [HR 1.87(95% CI 1.11–3.14)] were also associated with increased mortality risk in our cohort, p<0.05. Conclusion: Our findings suggested that placement of an AVF during the early stages of dialysis was associated with lower mortality compared to persistent CVC use among elderly patients. AVF placement appears to have a positive impact on survival outcomes, even in those who started dialysis with a CVC. (AU)

Introducción: El tipo de acceso vascular ideal para pacientes ancianos en hemodiálisis (HD) sigue siendo discutible. El objetivo de este estudio fue analizar la asociación entre los patrones de uso del acceso vascular en el primer año de HD y la mortalidad en pacientes ancianos. Métodos: Estudio retrospectivo unicéntrico de 99 pacientes incidentes en HD con edades ≥80años desde enero de 2010 hasta mayo de 2021. Los pacientes fueron categorizados según sus patrones de uso del acceso vascular en el primer año de HD: catéter venoso central (CVC) solo, CVC a fístula arteriovenosa (FAV), FAV a CVC y FAV solamente. Los datos clínicos iniciales se compararon entre los grupos. Los resultados de supervivencia se analizaron mediante las curvas de supervivencia de Kaplan-Meier y el modelo de riesgo proporcional de Cox. Resultados: En comparación con el CVC para la FAV, el riesgo de mortalidad fue significativamente mayor entre los pacientes que solo recibieron CVC y similar al grupo que solo utilizó FAV (HR: 0,93; IC95%: 0,32-2,51). Cardiopatía isquémica (HR: 1,74; IC95%: 1,02-2,96), niveles más bajos de albúmina (HR: 2,16; IC 95%: 1,28-3,64) y de hemoglobina (HR: 4,10; IC 95%: 1,69-9,92), y niveles más altos de proteína C reactiva (HR: 1,87; IC 95%: 1,11-3,14) también se asociaron con un mayor riesgo de mortalidad en nuestra cohorte (p<0,05). Conclusión: Nuestros hallazgos sugirieron que la colocación de una FAV durante las primeras etapas de la diálisis se asoció con una menor mortalidad en comparación con el uso persistente de CVC en pacientes ancianos. La colocación de una FAV parece tener un impacto positivo en los resultados de supervivencia, incluso en aquellos que comenzaron la diálisis con un CVC. (AU)

Efficiency of ferric carboxymaltose in non-dialysis CKD patients and its impact on kidney function: a prospective observational study.

BACKGROUND: Iron deficiency anemia occurs in most patients with non-dialysis chronic kidney disease (ND-CKD). Previous studies have suggested that intravenous (IV) iron therapy is more effective than oral iron in these patients. Clinical evidence relating the effects of IV iron on renal function is, however, limited. METHODS: Prospective observational study of adult patients with ND-CKD, anemia, iron deficiency, and estimated glomerular filtration rate (eGFR) < 60 mL/min/1.73 m2, treated with a single dose of 500 mg or 1000 mg of ferric carboxymaltose (FCM) and followed-up for 24 weeks. Primary outcome was FCM efficacy, assessed by comparing Hb, TSAT and ferritin at 24 weeks with those at baseline. Secondary outcome was FCM impact on renal function, evaluated by comparing eGFR over the same period. RESULTS: One hundred and forty patients were recruited: seventy-eight (55.7%) were treated with 1000 mg and 62 (44.3%) with 500 mg of FCM. 24 weeks after FCM administration, Hb increased 1.54 ± 1.99 g/dL (95% CI 1.09-1.99, p = 001) in the group treated with 1000 mg and 0.86 ± 1.4 g/dL (95% CI 0.53-1.22, p = 0.001) in those treated with 500 mg. TSAT increased in both groups but more in those treated with 1000 mg, and ferritin only increased in the latter. Estimated GFR showed a significant increase of 1.55 ± 6.86 mL/min/m2 (95% CI 0.05-3.09, p = 0.049), from a baseline of 27.73 ± 17.23 to 28.88 ± 18.02 mL/min/m2 in the group treated with 1000 mg. CONCLUSIONS: Our findings suggested that IV FCM therapy was effective in improving serum iron levels and anemia in ND-CKD stage 3 to 5 patients. Higher doses seem to be necessary to replace depleted iron stores. In our cohort, IV FCM therapy was associated with an improvement in renal function, particularly in those treated with higher doses of FCM.

Vascular access type and mortality in elderly incident hemodialysis patients.

INTRODUCTION: The ideal vascular access type for elderly hemodialysis (HD) patients remains debatable. The aim of this study was to analyze the association between patterns of vascular access use within the first year of HD and mortality in elderly patients. METHODS: Single-center retrospective study of 99 incident HD patients aged≥80 years from January 2010 to May 2021. Patients were categorized according to their patterns of vascular access use within the first year of HD: central venous catheter (CVC) only, CVC to arteriovenous fistula (AVF), AVF to CVC, and AVF only. Baseline clinical data were compared among groups. Survival outcomes were analyzed using Kaplan-Meier survival curves and Cox's proportional hazards model. RESULTS: When compared with CVC to AVF, mortality risk was significantly higher among CVC only patients and similar to AVF only group [HR 0.93 (95% CI 0.32-2.51)]. Ischemic heart disease [HR 1.74 (95% CI 1.02-2.96)], lower levels of albumin [HR 2.16 (95% CI 1.28-3.64)] and hemoglobin [HR 4.10(95% CI 1.69-9.92)], and higher levels of c-reactive protein [HR 1.87(95% CI 1.11-3.14)] were also associated with increased mortality risk in our cohort, p<0.05. CONCLUSION: Our findings suggested that placement of an AVF during the early stages of dialysis was associated with lower mortality compared to persistent CVC use among elderly patients. AVF placement appears to have a positive impact on survival outcomes, even in those who started dialysis with a CVC.

Thrombotic microangiopathy in a patient with systemic lupus erythematosus and anti-factor H autoantibodies.

Thrombotic microangiopathy (TMA) is a serious complication that may occur in patients with systemic lupus erythematosus (SLE), adversely affecting the prognosis and increasing mortality. The pathogenesis of TMA in these patients may be multifactorial and overlap between different entities may exist. We present a case of a 24-year-old man, previously diagnosed with SLE, class IV lupus nephritis, and antiphospholipid antibody syndrome, who was admitted with acute kidney injury, severe pancytopenia, and other features consistent with lupus flare. A clinical TMA diagnosis was made and the patient was treated with plasmapheresis, rituximab and immunoglobulin endovenous (EV) infusions. Hemodialysis was initiated during hospitalization and, despite the hematological recovery, the patient remained dialysis dependent. The complementary study revealed high levels of anti-factor H (fH) autoantibodies with no pathogenic mutations on complement genes (namely CFHR1 and CFHR3). Initially, the most likely cause of TMA seemed to be secondary to SLE, but the presence of anti-fH antibodies in our patient may suggest a concomitant complement-mediated TMA.

Overhydration, A New Risk Factor for Peritonitis in Peritoneal Dialysis.

INTRODUCTION: Overhydration (OH) remains a recurrent problem in peritoneal dialysis (PD), with deleterious effect in outcomes. Recent evidence suggests a direct relation between OH and increased peritonitis risk. The mechanisms of this connection are not well defined, but gut wall edema and malnutrition are probably involved. METHODS: Our aim was to assess OH as a risk factor for peritonitis in patients on PD. Retrospective study was done in a PD program with a bio impedance analysis. The investigator reviewed patient charts and documents. The Fresenius® Body Composition Monitor was used to obtain hydration parameters. OH was considered when Overhydration/Extracellular Water (OH/ECW) parameter was over 15% of the dry weight. The diagnosis of peritonitis was made according to the International Society of Peritoneal Dialysis guidelines. Associations between peritonitis rate and the collected variables were assessed using Chi-square test and Pearson's correlation. RESULTS: An association between OH and the risk of peritonitis was established. CONCLUSION: OH is prevalent in our patients undergoing PD and it is a modifiable risk factor for peritonitis. The bio impedance analysis is economical and should be used in association with a physical exam and treatment results to achieve the normo-hydrated status in those patients.

Hypertension-associated thrombotic microangiopathy in an adult patient with complement factor H autoantibodies and a rare heterozygous variant in the CFH gene.

Atypical hemolytic uremic syndrome (aHUS) is a rare disease characterized by microangiopathic hemolytic anemia, thrombocytopenia, and renal injury, which results from thrombotic microangiopathy (TMA) within the glomerular capillaries and arterioles. We report a case of a biopsy-proven renal TMA attributed to hypertension in a 42-year-old woman with undiagnosed alternative complement pathway dysregulation resulting from a rare association between complement factor H (CFH) autoantibodies and a heterozygous variant in the CFH gene. We propose that severe hypertension triggered an over-activation of the alternative complement pathway in a patient with genetic predisposition. In this case, blood pressure control allowed normalization of hematologic parameters and partial recovery of renal function, supporting the idea that shear stress is an important complement-amplifying factor.

Idiopathic Retroperitoneal Fibrosis: Long-term Risk and Predictors of Relapse.

RATIONALE & OBJECTIVE: Idiopathic retroperitoneal fibrosis (IRF) is a rare disorder of unknown cause. Medical therapy can induce remission, but disease relapses are common. This study sought to characterize long-term outcomes of IRF and the factors associated with disease recurrences. STUDY DESIGN: Retrospective cohort study. SETTING & PARTICIPANTS: Retrospective analysis of 50 patients with IRF prospectively followed up for 8.9 (IQR, 4.7-12.7) years at a tertiary-care referral center. EXPOSURES: Demographic, clinical, treatment, and laboratory parameters, including measures of autoimmunity. OUTCOME: Disease relapse. ANALYTICAL APPROACH: Proportional hazards analysis for the subdistribution of competing risks. RESULTS: 49 patients received medical treatment and 35 underwent interventional procedures. All patients experienced a clinical response (defined as regression of disease-related symptoms and hydronephrosis, and decrease in the maximal transverse diameter of the retroperitoneal mass on computed tomography of >50%), 44 of whom responded within 1 year. The remaining 6 responded over a median of 2.95 years after starting therapy. 40 patients were alive at last observation, 1 receiving maintenance dialysis and 15 with estimated glomerular filtration rate < 60mL/min/1.73m2. Patient survival at 5, 10, and 15 years was 95%, 84%, and 68%, respectively. 19 (38%) patients had at least 1 relapse (occurring a median of 5.19 years after starting therapy), defined as an increase in serum creatinine level of at least 30% or recurrence/development of hydronephrosis and ≥20% increase in the maximal transverse diameter of the retroperitoneal mass on computed tomography. Cumulative incidences of relapse at 5, 10, and 15 years were 21%, 41%, and 48%, respectively. Baseline antinuclear antibody positivity and male sex were associated with relapse (subdistribution hazard ratios [sHRs] of 5.35 [95% CI, 2.15-13.27] and 4.94 [95% CI, 1.32-18.57], respectively), while higher corticosteroid therapy dosage at 1 year (sHR for relapse per 1-mg/d greater dosage, 0.91 [95% CI, 0.84-0.98]) and treatment with prednisone alone or with tamoxifen (sHR for relapse of 0.25 [95% CI, 0.07-0.85] vs other therapies) were associated with lower rate of relapse. LIMITATIONS: Small sample size and variable approaches to therapy. CONCLUSIONS: IRF relapses were common and were experienced more frequently by male patients. Corticosteroids alone or with tamoxifen were associated with a lower rate of relapse. The strong association of antinuclear antibody positivity with relapse supports the hypothesis of an autoimmune pathogenesis of IRF.

Diastolic Dysfunction, an Underestimated New Challenge in Dialysis.

Heart failure (HF) is very common in the general population and specifically in CKD patients due to higher prevalence of traditional and CKD-related risk factors. In particular, HF with preserved ejection fraction (HFpEF) can affect over 50% of dialysis patients. However, little is known about this entity in CKD. It has been inadequately recognized over time and few data exist regarding clinical profiles and outcomes in dialysis patients. The aim of this paper is to do a critical appraisal of the diagnosis, clinical impact, and management of HFpEF with a focus on new diagnostic criteria and its impact on dialysis.

Does cyclophosphamide still play a role in glomerular diseases?

Cyclophosphamide is a prodrug that is converted to inactive carboxy-cyclophosphamide, acrolein and phosphoramide mustard, an agent that adds alkyl groups to oxygen and nitrogen atoms of guanine, one of the four nitrogen bases that form the DNA nucleotides, causing DNA cross-links and introducing DNA breaks. These cytotoxic and mutagenic effects mainly occur in proliferating cells. Repair mechanisms may prevent DNA damage in quiescent cells, but they may be insufficient to contrast the side effects of cyclophosphamide if high doses of the drug are used. Most adverse events are dose- and age-dependent. Phosphoramide mustard can cause bone marrow toxicity, gonadal toxicity, and may favor the development of leukemia, bladder cancer and other types of malignancy. Acrolein can produce hemorrhagic cystitis and even bladder fibrosis when given for prolonged periods. A number of precautional measures should be taken to prevent these untoward events. In particular, long-term administration and high doses of cyclophosphamide should be avoided whenever possible. Today the indications to cyclophosphamide in glomerular diseases are more restricted than in the past, but the drug is still used as a steroid-sparing agent in steroid-sensitive minimal change disease and focal segmental glomerulosclerosis. In membranous nephropathy, cyclophosphamide, alternated or associated with corticosteroids, proved to be beneficial in obtaining remission of nephrotic syndrome and preserving renal function. Cyclophosphamide is considered as a first-line treatment for rapidly progressive glomerulonephritis and the hectic phases of lupus nephritis. In conclusion, cyclophosphamide is a cheap drug that may be useful in a number of glomerular diseases but it may lead to severe side effects. A close monitoring of blood count and clinical conditions, as well as low cumulative doses of cyclophosphamide are strongly recommended when using the drug in patients with renal diseases.

Glomerular Filtration Rate and Initiation of Dialysis.

The proportion of patients with advanced chronic kidney disease (CKD) initiating dialysis at higher glomerular filtration rate (GFR) has increased over the past decade. Recent data suggest that it may be associated with increased mortality. The goal of this analysis was to compare survival outcomes in patients with early and late start dialysis. We performed a retrospective analysis of hemodialysis (HD) incident patients from 1 January 2010 to 30 September 2014. Patients were classified into two groups by estimated GFR at dialysis initiation (eGFR ≥10: early start and <10 mL/min per 1.73m2 : late start). Logistic regression was used to evaluate factors associated with early and late dialysis start, and Kaplan-Meier graphs and Cox regression models in survival analysis. In this total incident population (N = 235), 42 patients had an early dialysis start. Compared with the group with an eGFR of <10 mL/min per 1.73 m2 at dialysis start, a Cox model showed an incremental increase in mortality associated with earlier dialysis start (P = 0.027). Independent factors (P < 0.05) associated with mortality in the multivariable Cox model in early dialysis start were: hypertension (HR 9.32, CI: 1.34-17.87), diabetes (HR 1.8, CI: 0.4-13.2) and albumin <3.5 g/dL (HR 1.5, CI: 0.8-6.2). Older patients (HR 0.084, CI: 0.008-0.863) with low phosphorus levels (HR 0.02, CI: 0.0-0.527) also had statistically significant results, although they showed a reduced risk of mortality. Early dialysis initiation was associated with an increased mortality risk, arguing against aggressive early dialysis initiation based primarily on eGFR alone.

Dabigatran-Related Nephropathy in a Patient with Undiagnosed IgA Nephropathy.

Dabigatran is a direct thrombin inhibitor used as an alternative to warfarin for long term anticoagulation. Warfarin-related nephropathy is an increasingly recognized entity, but recent evidence suggests that dabigatran can cause a WRN-like syndrome. We describe a case of a biopsy-proven anticoagulant nephropathy related to dabigatran in a patient with IgA nephropathy and propose that, despite the base glomerular disease, acute kidney injury was due to tubular obstruction by red blood cells and heme-associated tubular injury, and through a mechanism involving inhibition of anticoagulation cascade and barrier abnormalities caused by molecular mechanisms.