Borja Quiroga

Renal biopsy in very elderly patients: data from the Spanish Registry of Glomerulonephritis.

Background: Studies on renal histology results in very elderly patients are extremely rare. Methods: We analyzed histology and clinical findings in patients aged over 85 years undergoing renal biopsy and whose data were included in the Spanish Registry of Glomerulonephritis between 1994 and 2009. Results: A total of 17,680 native kidney biopsies were taken: 71 (0.4%) were from patients aged over 85 years. Acute kidney injury (AKI) was the main indication for biopsy (47%), followed by nephrotic syndrome (32%). Amyloidosis was the most common histological diagnosis (16.9%), followed by crescentic glomerulonephritis type 3 associated with systemic vasculitis (14.1%). When histological findings were correlated with clinical syndromes, we found that amyloidosis was the leading cause of AKI (18.8%), and also the main determinant of nephrotic syndrome, with the same frequency as membranous nephropathy (22%). Crescentic glomerulonephritis type 3 associated with vasculitis was related to a greater diversity of clinical syndromes, especially chronic kidney disease (40%) and AKI (40%). Conclusions: Renal biopsy in the very elderly provides us with useful information, despite the advanced age of the patients. AKI and nephrotic syndrome are the main indication for renal biopsy in this subgroup of patients, and amyloidosis is the most frequent histological pattern associated with both syndromes.

Effects of pentoxifylline on inflammatory parameters in chronic kidney disease patients: a randomized trial.

BACKGROUND Pentoxifylline (PTF) is a potential therapeutic agent in chronic kidney disease due to its antiinflammatory and antiproteinuric effects that may influence the progression of renal disease. SUBJECTS AND METHODS We conducted a prospective randomized trial of 91 patients with estimated glomerular filtration rate (eGFR) <60 ml/min, calculated with 4-variable Modification of Diet in Renal Disease (MDRD-4) Study equation. Patients were randomly assigned to treatment with PTF 400 mg (twice a day) (n=46) or to continue their usual therapy (n=45). Clinical, biochemical and inflammatory parameters were measured at baseline, and at 6 and 12 months of treatment. The objective of the study was to analyze the effect of PTF treatment on inflammatory markers and secondarily the effect on renal disease progression. RESULTS Baseline characteristics were similar in the 2 groups. High-sensitivity C-reactive protein (hs-CRP), serum fibrinogen and TNF-alpha decreased significantly in patients treated with PTF in comparison with the control group at 12 months (p=0.002, p=0.001 and p=0.000, respectively). Median urinary albumin excretion did not decrease with PTF treatment. In the PTF group, there was no significant change in eGFR after 12 months (from 42.3 ± 10.2 to 44.7 ± 11.3 ml/min per 1.73 m(2)), whereas in the control group there was a worsening by the end of the study (from 40.1 ± 12.4 to 35.7 ± 13.4 ml/min per 1.73 m(2)) (p=0.000 between groups). CONCLUSIONS PTF treatment decreases inflammatory markers in chronic kidney disease and stabilizes renal function.

Present and Future in the Treatment of Diabetic Kidney Disease

Diabetic kidney disease is the leading cause of end-stage renal disease. Albuminuria is recognized as the most important prognostic factor for chronic kidney disease progression. For this reason, blockade of renin-angiotensin system remains the main recommended strategy, with either angiotensin converting enzyme inhibitors or angiotensin II receptor blockers. However, other antiproteinuric treatments have begun to be studied, such as direct renin inhibitors or aldosterone blockers. Beyond antiproteinuric treatments, other drugs such as pentoxifylline or bardoxolone have yielded conflicting results. Finally, alternative pathogenic pathways are being explored, and emerging therapies including antifibrotic agents, endothelin receptor antagonists, or transcription factors show promising results. The aim of this review is to explain the advances in newer agents to treat diabetic kidney disease, along with the background of the renin-angiotensin system blockade.

Albumin leakage in online hemodiafiltration, more convective transport, more losses?

Online hemodiafiltration (OL‐HDF) has now demonstrated some benefits in reducing mortality. It seems that rising convective volumes improve the outcomes, but the risks of it, such as albumin leakage, are not well defined yet. The aim of the present study was to evaluate the albumin leakage using two different filters with 20 and 30 L of post‐dilution OL‐HDF. In this cross‐sectional study, 20 prevalent patients receiving post‐dilution OL‐HDL were included. We analyzed two dialyzers: FX1000, FMC and Polyflux 210H, Gambro. During four consecutive dialysis sessions, monitors were programmed using control‐volume to obtain 20 or 30 L with both dialyzers. We collected albumin samples of the effluent at 5, 15, 30, 45 and 60 min and performed area under the curve (AUC) determinations for evaluating the losses. Mean patient age was 60 ± 9 years, and 70% were men. Albumin leakage was significant higher with Polyflux 210H when compared to FX 1000 FMC. A convective volume of 30 L produced greater albumin leakage than 20 L with both filters, though only with the FX 1000 FMC was it significant (minimum albumin leakage during first hour with FX 1000 FMC 20 L: 79.2 [0.0–175.7] mg; 30 liters: 403.3 [63.5–960.7] mg; with PF 210 Gambro 20 L: 869.1 [420.0–3214.7] mg; 30 L: 1841.7 [443.8–3417.5] mg). During OL‐HDF, convective transport causes albumin leakage at least during the first hour. The albumin concentration in the effluent differs according to the type of filter used and the convective volume.

Utility of bioimpedance spectroscopy (BIS) in the management of refractory hypertension in patients with chronic kidney disease (CKD)

BACKGROUND Expansion of extracellular volume (ECV) is a frequent cause of resistant hypertension (RHT) in patients with chronic kidney disease (CKD). The aim of this exploratory study was that of applying bioimpedance spectroscopy (BIS) for the identification of CKD patients with RHT and expansion of ECV, while trying to control blood pressure (BP) using an intensification of diuretic treatment. METHODS We included 50 patients with RHT and CKD who underwent BIS. In order to control BP, diuretic treatment was intensified in those patients with expansion of the ECV. In all other cases, another antihypertensive drug was added. RESULTS The mean age was 68.2 ± 10.4 years, 68% were male and 58% were diabetic. The mean estimated glomerular filtration rate (eGFR) was 50.7 ± 22.4 mL/min/1.72 m(2). Baseline systolic BP was 167.2 ± 8.6 mmHg and diastolic BP was 84.8 ± 9.5 mmHg. The mean number of antihypertensive drugs received was 3.8 ± 0.9. Expansion of ECV was recorded in 30 (60%) patients and was more frequent in diabetics and in patients with more albuminuria. At 6 months of follow-up, a decline of 21.4 ± 7.1 mmHg was observed in systolic BP in the patients with expansion of ECV, compared with a decrease of 9.4 ± 3.4 mmHg in the normal ECV group (P < 0.01). We did not find differences in the decrease in diastolic BP between the groups. Nine patients (30%) with ECV expansion who increased diuretic therapy reached the target blood pressure (BP) of <140/90 mmHg, when compared with only two patients (10%) who had normal ECV and in whom other antihypertensive drug was added. A total decrease in body water of 1.9 ± 1.1 L was observed in patients with ECV expansion who intensified diuretic treatment at the expense of a decline in ECV of 1.1 ± 1 L. eGFR remained stable in both groups (47.1 ± 21.1 versus 54.1 ± 25.2 mL/min/1.73 m(2); P = 0.37). CONCLUSIONS An increase in ECV as measured by BIS frequently occurs in RHT in patients with CKD. Diabetic and severe proteinuric patients are more exposed to expansion of ECV. BIS is a potentially useful method for identifying and treating patients with RHT and expansion of ECV. The hypothesis generated by this exploratory study needs to be tested in a randomized clinical trial.

Intraindividual Interleukin-6 Variations on the Cardiovascular Prognosis of Patients with Chronic Renal Disease

In chronic kidney disease (CKD) patients on dialysis, plasma interleukin (IL)-6 levels predict mortality better than other markers. Impact of intraindividual changes of inflammatory markers on cardiovascular (CV) events in CKD patients is unknown. The aim of this study is to demonstrate the relation between CV outcomes and variations of C-reactive protein (CRP), IL-6, IL-1β, and tumor necrosis factor (TNF)-α in CKD. Ninety patients (mean age: 68.5 ± 12.8 years) at different stages (1–4) of CKD were evaluated. Serum CRP, IL-6, IL-1β, and TNF-α were measured basally and after taking statins or angiotensin II receptor blockers. Three patterns were defined for each marker (baseline, mean of two measurements, and variation of the marker: increase or decrease after 6 months). During follow-up (mean time: 72.7 ± 19.8 months), 14 patients died, 11 were included on dialysis program, and 29 suffered a CV event. Patients with persistently elevated IL-6 values had higher risk to develop CV events [OR = 1.21 (1.11–1.32), p = 0.001]. Mean of two measurements of IL-6 was a better predictor for events than a single measurement of IL-6, CRP, TNF-α, and IL-1β. A mean of two determinations of plasma IL-6 greater than 6 pg/mL and previous peripheral vascular disease was related to an increased risk for CV events [2.34 (1.05–5.22), p = 0.037 and 2.95 (1.27–6.93), p = 0.011, respectively] in an adjusted Cox regression model. IL-6 is a better inflammatory marker than CRP, TNF-α, and IL1β at predicting CV events in CKD nondialysis patients. Mean of two measurements is better than simple determinations at predicting CV outcome.

Interarm systolic blood pressure as a predictor of cardiovascular events in patients with chronic kidney disease

BACKGROUND Increased interarm systolic blood pressure difference (IASBPD) is associated with mortality and cardiovascular (CV) events both in the general population and in patients at high CV risk. The aim of the present study was to assess the value of IASBPD ≥ 10 mmHg for predicting CV events in patients with chronic kidney disease (CKD). METHODS The study sample comprised 652 patients with CKD (age 67 ± 15 years, 58.1% men). Follow-up was 19 ± 5 months. We recorded increased IASBPD and related factors and assessed the predictive value of this variable for CV events. RESULTS We recorded diabetes mellitus in 136 patients (20.8%), history of CV disease in 213 (32.6%) and dyslipidaemia in 327 (50.1%). The mean glomerular filtration rate was 45.9 ± 18.9 mL/min/1.73 m(2), and the median albumin/creatinine ratio was 26(0-151) mg/g. IASBPD was ≥10 mmHg in 184 patients (28.1%). The factors associated with IASBPD ≥10 mmHg were age, systolic blood pressure levels, history of congestive heart failure, lower levels of high-density lipid cholesterol and higher use of hypertensive drugs. Fifty-eight patients (8.5%) developed a CV event during the follow-up. IASBPD ≥10 mmHg [HR, 1.802, 95%CI (1.054-3.079); P = 0.031] was an independent predictor of CV events. CONCLUSIONS Increased IASBPD is an independent predictor of CV events in CKD patients.

Diastolic Dysfunction and High Levels of New Cardiac Biomarkers as Risk Factors for Cardiovascular Events and Mortality in Hemodialysis Patients

Background/Aims: Cardiovascular events (CVEs) are the most frequent cause of death in hemodialysis (HD). We aim to determine cardiovascular and mortality risk factors. Methods: A historical cohort study was made of 211 prevalent HD patients [73 (60-80) years, 58% males] between 2005 and 2012. Demographic, laboratory test and echocardiographic values were recorded. During follow-up, CVEs and mortality were documented and analyzed. Results: 94 patients suffered a CVE. Age, history of cardiovascular disease (CVD), peripheral vascular disease, cardiac markers, systolic and diastolic dysfunction (DD) were associated to CVEs. Low albumin (RR 0.414, p = 0.002), DD (1.876, p = 0.038) and previous CVD (3.723, p < 0.001) were identified as independent predictors of CVEs. 98 patients died. Age, a history of CVD, peripheral vascular disease, cardiac markers, DD, dialysis vintage, and a vascular access different from autologous fistulae were associated to mortality. Low albumin (RR 0.499, p = 0.046), DD (RR 2.414, p = 0.017) and a vascular access different from autologous fistulae (RR 2.058, p = 0.034) were independent predictors of mortality. Conclusions: DD is an emergent risk factor for death and CVEs in dialysis. Low albumin is also a predictor for CVE. Non-autologous fistulae and low albumin are predictors for death. Nt-proBNP and hsTnT offer good information for identifying high-risk patients, but they do not predict events independently as they are only cardiac damage markers.

Progresión de la enfermedad renal crónica en pacientes con enfermedad poliquística autosómica dominante

OBJECTIVES The aim of this study was to analyse the factors influencing chronic kidney disease (CKD) progression in patients with autosomal dominant polycystic kidney disease (ADPKD). MATERIAL AND METHOD We studied 101 patients (mean age: 43 +/- 17.3 years, 43.56% male) followed during a median (interquartile range) follow-up time of 69 (35-128) months from 1997 to 2010. The primary end point was: time to a 50% decrease of estimated glomerular filtration rate (eGFR) (CKD-EPI) since the first-time visit and/or time to initiation of renal replacement therapy, and the annual mean change of eGFR was also analysed. Clinical and demographic data, blood pressure, concomitant medications, and analytical parameters were collected at each visit. Baseline kidney size was also recorded by ultrasound. RESULTS Thirty-one patients achieved the primary end point after a median (IQR) time of 102 (53-131) months. Those patients who achieved the primary end point had higher SBP and DBP (P=0.017 and P=0.001), higher LDL-cholesterol (P=0.011), higher creatinine (P=0.006), higher uricemia (P=0.041), more severe proteinuria (P=0.033) and greater kidney size (P=0.05). The mean annual eGFR change was of -3.52 +/- 7.3ml/min/1.73m2. Forty-nine patients had a rapid decline in renal function: Group A (higher than -3.52ml/min/1.73m2) and 52 patients had a lower renal disease progression: Group B (<-3.2 ml/min/1.73 m2). Adjusted Cox regression analysis showed that higher SBP and younger age at the first visit were independent variables for poorer renal outcome (P=0.026). CONCLUSIONS Initial kidney function, proteinuria, renal size, hypercholesterolemia, hyperuricemia, and SBP are the factors that influence CKD progression in ADPKD. SBP and younger age at diagnosis are the only factors that maintain their independent predictive value in a multivariant analysis.

Pulmonary hypertension is an independent predictor of cardiovascular events and mortality in haemodialysis patients.

The evidence about prevalence, associated factors of pulmonary hypertension (PH) and its impact on patients outcomes is limited.