Treatment of Chronic Heart Failure in Advanced Chronic Kidney Disease: The HAKA Multicenter Retrospective Real-World Study.

INTRODUCTION: Chronic heart failure (HF) has high rates of mortality and hospitalization in patients with advanced chronic kidney disease (aCKD). However, randomized clinical trials have systematically excluded aCKD population. We have investigated current HF therapy in patients receiving clinical care in specialized aCKD units. METHODS: The Heart And Kidney Audit (HAKA) was a cross-sectional and retrospective real-world study including outpatients with aCKD and HF from 29 Spanish centers. The objective was to evaluate how the treatment of HF in patients with aCKD complied with the recommendations of the European Society of Cardiology Guidelines for the diagnosis and treatment of HF, especially regarding the foundational drugs: renin-angiotensin system inhibitors (RASi), angiotensin receptor blocker/neprilysin inhibitors (ARNI), beta-blockers (BBs), mineralocorticoid receptor antagonists (MRAs), and sodium-glucose cotransporter-2 inhibitors (SGLT2i). RESULTS: Among 5,012 aCKD patients, 532 (13%) had a diagnosis of HF. Of them, 20% had reduced ejection fraction (HFrEF), 13% mildly reduced EF (HFmrEF), and 67% preserved EF (HFpEF). Only 9.3% of patients with HFrEF were receiving quadruple therapy with RASi/ARNI, BB, MRA, and SGLT2i, but the majority were not on the maximum recommended doses. None of the patients with HFrEF and CKD G5 received quadruple therapy. Among HFmrEF patients, approximately half and two-thirds were receiving RASi and/or BB, respectively, while less than 15% received ARNI, MRA, or SGLT2i. Less than 10% of patients with HFpEF were receiving SGLT2i. CONCLUSIONS: Under real-world conditions, HF in aCKD patients is sub-optimally treated. Increased awareness of current guidelines and pragmatic trials specifically enrolling these patients represent unmet medical needs.

Prescribing the dialysis dose and treatment frequency in home haemodialysis.

BACKGROUND: There is growing interest in home haemodialysis (HHD) performed with low-flow dialysate devices and variable treatment schedules. The target standard Kt/V (stdKt/V) should be 2.3 volumes/week, according to KDOQI guidelines (2015). The current formula for stdKt/V does not help prescribe the dialysis dose (eKt/V) and treatment frequency (TF). The aim of this study was to obtain a formula for stdKt/V that is able to define the minimum required values of eKt/V and TF to achieve the targeted stdKtV. METHODS: Thirty-eight prevalent patients on HHD were enrolled. A total of 231 clinical datasets were available for urea modelling using the Solute-Solver software (SS), recommended by KDOQI guidelines. A new formula (stdKt/V = a + b × Kru + c × eKt/V) was obtained from multivariable regression analysis of stdKt/V vs eKt/V and residual kidney urea clearance (Kru). The values of coefficients a, b and c depend on the treatment schedules and the day of the week of blood sampling for the kinetic study (labdayofwk) and then vary for each of their foreseen 62 combinations. For practical purposes, we used only seven combinations, assuming Monday as a labdayofwk for each of the most common schedules of the 7 days of the week. RESULTS: The stdKt/V values obtained with SS were compared with the paired ones obtained with the formula. The mean ± standard deviation stdKt/V values obtained with SS and the formula were 3.043 ± 0.530 and 2.990 ± 0.553, respectively, with 95% confidence interval +0.15 to -0.26. A 'prescription graph' was built using the formula to draw lines expressing the relationship between Kru and required eKt/V for each TF. Using this graph, TF could have been reduced from the delivered 5.8 ± 0.8 to 4.8 ± 0.8 weekly sessions. CONCLUSIONS: The new formula for stdKtV is reliable and can support clinicians to prescribe the dialysis dose and TF in patients undergoing HHD.

Validation of formulas calculating normalized protein catabolic rate in patients undergoing home hemodialysis.

Depner and Daugirdas developed a simplified formula to estimate the normalized protein catabolic rate in patients on twice- or thrice-weekly hemodialysis (JASN, 1996). The aim of our work was to establish formulas in more frequent schedules and validate them in home-based hemodialysis patients. We realized that the structure of Depner and Daugirdas' normalized protein catabolic rate formulas has a general meaning and can be expressed as PCRn = C0/[a + b*(Kt/V) + c/(Kt/V)] + d, where C0 is pre-dialysis blood urea nitrogen, Kt/V is dialysis dose, a, b, c, d are the specific coefficients for each combination of home-based hemodialysis schedules and the day of blood sampling. The same applies to the formula that adjusts C0 (C'0) for residual kidney clearance of blood water urea (Kru) and urea distribution volume (V): C'0 = C0*[1 + (a1 + b1/(Kt/V))*Kru/V]. On this basis, we computed the six coefficients (a, b, c, d, a1, b1) for each of the 50 possible combinations and simulated a total of 24,000 weekly dialysis cycles using the Daugirdas Solute Solver software recommended by the KDOQI 2015 guidelines. From the associated statistical analyses we obtained 50 sets of coefficient values, which were validated comparing the paired normalized protein catabolic rate values (i.e., those estimated with our formulas with those modeled with Solute Solver) in 210 datasets of 27 patients on home-based hemodialysis. The mean values ± SD were 1.06 ± 0.262 and 1.07 ± 0.283 g/kg/day, respectively, with a mean difference of 0.004 ± 0.034 g/kg/day (p = 0.11). The paired values were highly correlated (R2 = 0.99). In conclusion, even if the coefficient values were validated in a relatively small sample of patients, they allow an accurate estimation of normalized protein catabolic rate in home-based hemodialysis patients.

Is peritoneal dialysis suitable technique CKD patients over 65 years? A prospective multicenter study.

BACKGROUND: Chronic kidney disease (CKD) is increasing in patients older than 65 years and is related to morbidity, frailty, and dependence. Peritoneal dialysis (PD) has classically been associated with young patients with an active life. HYPOTHESIS: PD should be offered to patients over 65 years. We search for any unfavorable results that may advice not to recommend PD therapy for this group. OBJECTIVE: To describe PD treatment and outcomes in patients > 65 years, to compare their results with patients < 65 years and to identify areas with room for improvement in a real-life study. STUDY: Prospective, observational, and multicenter study performed in incident PD patients, from January 2003 until January 2018. RESULTS: We included 2,435 PD patients, 31.9% were older than 65 years; there was a difference of 25 years between both groups. Median follow up was 2.1 years. Older than 65 years group had more comorbidity: Diabetes (29.5% vs 17.2%; p < 0.001), previous CV events 34.5% vs 14.0%; p < 0.001), Charlson index (3.8 vs 3.0; p < 0.001). We did not find differences in efficacy and PD adequacy objectives fulfillment, anaemia management or blood pressure during follow-up. Peritonitis rate was higher in older 65 years group (0.65 vs 0.45 episodes/patient/year; p < 0.001), but there was not differences in germs, admission rate and follow up. Mortality was higher in older 65 years group (28.4% vs 9.4%) as expected. PD permanence probability was similar (2.1 years). The main cause of PD withdrawal was transplant in group < 65 years (48.3%) and transfer to HD in group > 65 years. The main reason was caregiver or patient fatigue (20.2%), and not technique failure (7.3%). Multivariate Cox regression analysis showed a relation (HR [95%CI]) between mortality and age > 65 years 2.4 [1.9-3.0]; DM 1.6 [1.3-2.1]; CV events 2.1 [1.7-2.7]. Multivariate Cox regression analysis identify a relation between technique failure and age > 65 years 1.5 [1.3-1.9]; DM 1.6 [1.3-1.9] and previous transplant 1.5 [1.2-2.0]. CONCLUSION: Patients older than 65 years fulfilled PD adequacy criteria during the follow up. We believe PD is a valid option for patients older 65 years. It is necessary to try to prevent infections and patient/caregiver fatigue, to avoid HD transfer for reasons not related to technique failure.

Survival and renal recovery after acute kidney injury requiring dialysis outside of intensive care units.

BACKGROUND: The incidence of acute kidney injury requiring dialysis (AKI-D) is increasing globally and it is usually associated to chronic kidney disease (CKD) and high mortality. Literature is lacking in short- and intermediate-term data on recovery of renal function after acute kidney injury (AKI). OBJECTIVES: The objective was to evaluate the overall survival and renal recovery after an episode of AKI requiring dialysis out of intensive care units (ICUs). MATERIALS AND METHODS: Retrospective study including patients admitted in two nephrology units along a period of 2 years. Patients admitted to ICUs and renal transplant patients were excluded. Baseline renal function, mortality and glomerular filtration rate (GFR) improvement were evaluated. RESULTS: 151 consecutive adult patients with AKI requiring renal replacement therapy (RRT) were included. Mean age was 70.5 ± 15.2 years, 60.3% were males. Median baseline creatinine (bCr) and baseline GFR (bGFR) were 1.4 mg/dL and 46 mL/min/1.73 m2, respectively. After 1 year of follow-up, we completed the monitoring of 94 patients: 64.9% had died, 10.6% were alive on dialysis and 24.5% were alive without need for RRT. Patients with bGFR > 60 mL/min/1.73 m2 prior to AKI episode had a slower but sustained GFR improvement through the follow-up in comparison with patients with bGFR < 60 mL/min/1.73 m2 whose recovery was incomplete. CONCLUSIONS: Patients with AKI requiring RRT have high short- and intermediate-term mortality and some require maintenance dialysis. Patients with GFR > 60 mL/min/1.73 m2 prior to AKI had a renal recovery closer to the basal renal function than in patients with a previously diminished GFR.

The role of an electronic alert system to detect acute kidney injury in hospitalized patients: DETECT-H Project.

BACKGROUND AND AIMS: Acute kidney injury (AKI) is associated with higher mortality and length of stay (LOS) for hospitalized patients. To improve outcomes, an electronic detection system could be a useful tool for early diagnosis. METHODS: A fully automated real-time system for detecting decreased glomerular filtration rate in adult patients was developed in our hospital, DETECT-H project. AKI was established according to KDIGO guidelines. RESULTS: In six months, 1241 alerts from 11,022 admissions were issued. Overall incidence of AKI was 7.7%. Highest AKI stage reached was: stage 1 (49.8%), 2 (24.5%) and 3 (25.8%), in-hospital mortality was 10.9%, 22.7%, 33.9% respectively and 57.1% in AKI requiring dialysis; mortality in stable CKD was 4.3%. Median LOS was 8 days versus 5 days for all patients. AKI was associated with a mortality of 3.18 (95% CI 1.80-5.59) and a LOS 1.52 (1.11-2.08) times as high as that for admissions without AKI. Multivariate analysis indicated that a LOS higher than 8 days was associated with AKI. Previous CKD was noted in 31.9% and AKI in 45.3% at discharge. As compared to the use of the detect system, only one third of CKD patients and half of AKI episodes were identified. CONCLUSIONS: CKD and in-hospital AKI are under-recognized entities. Mortality and LOS are increased in-hospital patients with renal dysfunction. AKI severity was associated with higher mortality and LOS. An automated electronic detection system for identifying renal dysfunction would be a useful tool to improve renal outcomes.

Very low doses of direct intravenous iron in each session as maintenance therapy in hemodialysis patients.

BACKGROUND: Intravenous (IV) iron supplementation is widely used in hemodialysis (HD) patients to treat their periodic losses. However, the ideal dose and frequency is unknown. The goal of the study is to see if a 20 mg dose of iron IV at the end of each session of HD as iron maintenance is better than the iron prior therapy. We analyze the erythropoiesis activity (EA) and functional iron (FI) after four weeks of treatment. METHODS: In 36 patients, we measure reticulocyte count and content of hemoglobin reticulocyte (CHr) as EA and FI markers, respectively, before and after the treatment. Before the study, 23 patients received another different therapy with IV iron as maintenance therapy. RESULTS: Reticulocyte count: 49.7 ± 23.8 × 10(3) before and 47.2 ± 17.2 × 10(3) after the treatment (p= 0.51). The CHr: 34.8 ± 3.7 pg and 34.4 ± 3.5 pg, respectively, (p= 0.35), showing an excellent correlation with the other FI markers (serum iron r = 0.6; p = 0.001; saturation transferrin r = 0.49; p = 0.004); that is not shown with the serum ferritin (r = 0.23; p = 0.192) or the hepcidin levels (r = 0.22; p = 0.251). There was not a correlation between the C-Reactive Protein, reticulocyte count, and CHr. The 13 patients who did not receive the iron prior to the study showed high FI levels, but not an increased of the serum ferritin or the serum hepcidin levels. CONCLUSIONS: The administration of a small quantity of iron at the end of every HD session keeps the EA and the FI levels and allows reducing the iron overload administered and/or decreasing the iron stores markers in some patients.