Epidemiology of hyperkalemia in chronic kidney disease. / Epidemiología de la hiperpotasemia en la enfermedad renal crónica.

BACKGROUND: Hyperkalaemia is a significant electrolyte imbalance in chronic kidney disease (CKD). Renin-angiotensin-aldosterone system inhibitors (RAASi) have beneficial cardio-renal properties, although they can often cause hyperkalaemia. OBJECTIVE: To examine the prevalence of hyperkalaemia in CKD, identify factors associated with its appearance and the relationship between hyperkalaemia and mortality. PATIENTS AND METHODS: Retrospective observational study on patients with CKD in the period 1971-2017. The population was categorised into 3groups: Group 1, patients with CKD without renal replacement therapy; Group 2, patients on haemodialysis; and Group 3, patients on continuous ambulatory peritoneal dialysis. RESULTS: A total of 2,629 patients were evaluated. The prevalence observed in the different groups was: 9.6%, 16.4% and 10.6%, respectively. Risk factors related to the appearance of hyperkalaemia in the CKD group were glomerular filtration rate (GFR) (P<.001), plasma creatinine (P<.001), plasma sodium (P<.001), haemoglobin (P=.028), diastolic blood pressure (P=.012), intake of ACE inhibitors and/or angiotensin ii receptor blockers (P=.008), treatment with metformin (P<.001) and diabetes (P=.045). Treatment with RAASi significantly increased hyperkalaemia as GFR decreased, as well as in patients with diabetes or heart failure. CONCLUSIONS: Hyperkalaemia is a frequent metabolic alteration in CKD patients that increases in the presence of drugs with beneficial cardio-renal properties (RAASi), which means that patients often lose the benefit associated with these drugs. New, recently-appearing non-absorbable compounds, which bind to potassium in the gastrointestinal tract, enhancing faecal excretion and thus maintaining the cardio-renal benefit of the RAASi, could be relevant in the progress of patients with CKD.

Association between recurrence of acute kidney injury and mortality in intensive care unit patients with severe sepsis.

BACKGROUND: Acute kidney injury (AKI) occurs in more than half critically ill patients admitted in intensive care units (ICU) and increases the mortality risk. The main cause of AKI in ICU is sepsis. AKI severity and other related variables such as recurrence of AKI episodes may influence mortality risk. While AKI recurrence after hospital discharge has been recently related to an increased risk of mortality, little is known about the rate and consequences of AKI recurrence during the ICU stay. Our hypothesis is that AKI recurrence during ICU stay in septic patients may be associated to a higher mortality risk. METHODS: We prospectively enrolled all (405) adult patients admitted to the ICU of our hospital with the diagnosis of severe sepsis/septic shock for a period of 30 months. Serum creatinine was measured daily. 'In-ICU AKI recurrence' was defined as a new spontaneous rise of ≥0.3 mg/dl within 48 h from the lowest serum creatinine after the previous AKI episode. RESULTS: Excluding 5 patients who suffered the AKI after the initial admission to ICU, 331 patients out of the 400 patients (82.8%) developed at least one AKI while they remained in the ICU. Among them, 79 (19.8%) developed ≥2 AKI episodes. Excluding 69 patients without AKI, in-hospital (adjusted HR = 2.48, 95% CI 1.47-4.19), 90-day (adjusted HR = 2.54, 95% CI 1.55-4.16) and end of follow-up (adjusted HR = 1.97, 95% CI 1.36-2.84) mortality rates were significantly higher in patients with recurrent AKI, independently of sex, age, mechanical ventilation necessity, APACHE score, baseline estimated glomerular filtration rate, complete recovery and KDIGO stage. CONCLUSIONS: AKI recurred in about 20% of ICU patients after a first episode of sepsis-related AKI. This recurrence increases the mortality rate independently of sepsis severity and of the KDIGO stage of the initial AKI episode. ICU physicians must be aware of the risks related to AKI recurrence while multiple episodes of AKI should be highlighted in electronic medical records and included in the variables of clinical risk scores.

Anti-parathyroid treatment effectiveness and persistence in incident haemodialysis patients with secondary hyperparathyroidism / Efectividad y persistencia de los tratamientos del hiperparatiroidismo secundario en pacientes incidentes en hemodiálisis

Antecedentes: El inicio y la discontinuación del tratamiento antiparatiroideo son decisiones importantes en los pacientes en hemodiálisis crónica (HD) en los que la carga de pastillas es con frecuencia excesiva. El objetivo de este estudio es describir de tratamiento del hiperparatiroidismo secundario (sHPT) en pacientes en HD. Métodos: Estudio de cohorte, observacional retrospectivo de pacientes europeos incidentes en HD con sHPT a quienes se prescribió calcitriol o alfacalcidol (calcitriol-alfa), paricalcitol o cinacalcet. Resultados: Se incluyeron en el análisis pacientes que recibieron por primera vez calcitriol-alfa (N=2259), paricalcitol (N=1689) y cinacalcet (N=1245). Los valores sericos de hormona paratiroidea intacta (iPTH) disminuyeron tras iniciación con todos los tratamientos; los valores de calcio y fosforo serico se elevaron en respuesta al tratamiento con activadores de vitamina D pero disminuyeron con cinacalcet. Aproximadamente un tercio de los pacientes que recibieron calcitriol alfa y paricalcitol, y menos de una cuarta parte de los de cinacalcet discontinuaron el tratamiento. Aunque los tres grupos tuvieron descensos comparables de iPTH al momento de la interrupción del tratamiento, sin embargo difirieron en los valores de calcio y fosforo serico. Tras la interrupción, la evolución de los parámetros de laboratorio fué diferente según la modalidad de tratamiento: mientras que la iPTH se elevó en las tres modalidades, el calcio y fosforo sericos disminuyeron en los pacientes que estaban siendo tratados con calcitriol-alfa y paricalcitol en el momento de la interrupción y aumentaron en los que lo hacían con cinacalcet. Conclusiones: En condiciones clínicas que representan la práctica diaria, alcanzar y mantener los valores recomendados para el control del sHPT se consigue más frecuentemente con cinacalcet que con compuestos activos de vitamina D (AU)

Background: Anti-parathyroid treatment initiation and discontinuation are important decisions in chronic haemodialysis (HD) patients, where pill burden is often excessive. The present study aimed to describe secondary hyperparathyroidism (sHPT) drug therapy changes in HD patients. Methods: Retrospective observational cohort study of incident European HD patients with sHPT who were prescribed calcitriol or alfacalcidol (alpha calcitriol), paricalcitol or cinacalcet. Results: Treatment-naïve patients prescribed alpha calcitriol (N=2259), paricalcitol (N=1689) and cinacalcet (N=1245) were considered for analysis. Serum intact parathyroid hormone (iPTH) levels decreased post-initiation with all treatment modalities; serum calcium and phosphate levels increased in response to activated vitamin D derivatives but decreased with cinacalcet. Approximately one-third of alpha calcitriol and paricalcitol patients but less than one-quarter of cinacalcet patients discontinued treatment. Although the three groups had comparable serum iPTH control at the time of treatment discontinuation, they differed in terms of calcium and phosphate levels. Following discontinuation, the evolution of laboratory parameters differed by treatment modality: whilst iPTH increased for all three treatment groups, calcium and phosphate decreased in patients who were being treated with alpha calcitriol and paricalcitol at the time of discontinuation, and increased in those who had been treated with cinacalcet. Conclusions: In conditions of daily clinical practice, attaining and maintaining recommended biochemical control of sHPT appears to be more frequently achievable with cinacalcet than with activated vitamin D compounds (AU)

Anti-parathyroid treatment effectiveness and persistence in incident haemodialysis patients with secondary hyperparathyroidism.

BACKGROUND: Anti-parathyroid treatment initiation and discontinuation are important decisions in chronic haemodialysis (HD) patients, where pill burden is often excessive. The present study aimed to describe secondary hyperparathyroidism (sHPT) drug therapy changes in HD patients. METHODS: Retrospective observational cohort study of incident European HD patients with sHPT who were prescribed calcitriol or alfacalcidol (alpha calcitriol), paricalcitol or cinacalcet. RESULTS: Treatment-naïve patients prescribed alpha calcitriol (N=2259), paricalcitol (N=1689) and cinacalcet (N=1245) were considered for analysis. Serum intact parathyroid hormone (iPTH) levels decreased post-initiation with all treatment modalities; serum calcium and phosphate levels increased in response to activated vitamin D derivatives but decreased with cinacalcet. Approximately one-third of alpha calcitriol and paricalcitol patients but less than one-quarter of cinacalcet patients discontinued treatment. Although the three groups had comparable serum iPTH control at the time of treatment discontinuation, they differed in terms of calcium and phosphate levels. Following discontinuation, the evolution of laboratory parameters differed by treatment modality: whilst iPTH increased for all three treatment groups, calcium and phosphate decreased in patients who were being treated with alpha calcitriol and paricalcitol at the time of discontinuation, and increased in those who had been treated with cinacalcet. CONCLUSIONS: In conditions of daily clinical practice, attaining and maintaining recommended biochemical control of sHPT appears to be more frequently achievable with cinacalcet than with activated vitamin D compounds.

Long-Term Mortality among Hospitalized Non-ICU Patients with Acute Kidney Injury Referred to Nephrology.

BACKGROUND: Epidemiological studies of acute kidney injury (AKI) have focused on patients admitted to intensive care units (ICUs), and several have studied hospitalized non-ICU patients, but analysis of patients referred to Nephrology is sparse. We analyzed factors associated with short- and long-term morbimortality among hospitalized non-ICU patients with AKI who were referred to Nephrology. METHODS: A retrospective study with data prospectively collected from 170 non-ICU patients, with referral to the Nephrology Unit, recruited over a 4-year period, was performed. AKI was classified according to the criteria based on risk, injury, failure, loss of kidney function and end-stage kidney disease (RIFLE). Risk factors that could influence prognosis of AKI and long-term mortality were analyzed at admission. Early on, 1- and 10-year mortalities were correlated with AKI RIFLE class, clinical and demographic characteristics. RESULTS: Most patients were >65 years, with multiple comorbidities and frequent drug intake history. Median Charlson score was 6. Twenty-five percent of patients with previously unknown chronic kidney disease (CKD) were diagnosed with CKD during the study. Dialysis was required in 13.5% of patients. Hospital deaths were 22.4% and significantly associated with older age, RIFLE class L, higher peak serum creatinine, oliguria and decreased serum albumin levels. One-year (38.8%) and 10-year (68.8%) mortalities were significantly associated with age, prior cardiovascular disease, prior CKD and RIFLE class L. According to the Cox proportional hazard model, age, prior CKD and RIFLE class L were independent risk factors of death at 1 and 10 years. CONCLUSIONS: AKI in hospitalized non-ICU patients is associated with high early and late mortality. This study increases our understanding of AKI among this specific population and can improve their management.

[Dialysis and transplant. Spain in 2005]. / Informe de Situación de Diálisis y Trasplante en España, 2005.

In 2005, renal replace treatment (dialysis and transplant) was necessary for about 40,000 people, without being known the number accurate and either their basic characteristics, such as: time in treatment, modality or treatment changes. The presented data cover the 76% of the Spanish population and are the result of the cooperation among technicians of registries, nephrologists and transplant coordinations. 4,125 people started RRT in 2005, the total estimated acceptance rate for renal replacement therapy in adults in Spain was 126 pmp and regarding other European countries it locates us in an intermediate area. The incidence rate seems to keep stable in the last years although there were some differences among communities (from 104 pmp in Castile and Leon to 186 pmp in Canary Islands). Diabetes Mellitus is the most diagnosed cause of renal failure in 2005, more than 20% of patients, followed by vascular diseases. The estimated prevalence of renal replacement therapy in Spain at the end of 2005 was 903 pmp, with important variations among communities (from 806 pmp in Cantabria to 1056 pmp in Valencia Region). The 47% of prevalent RRT patients had a functioning transplant. Mortality on haemodialysis and peritoneal dialysis was 13.7% and 10.8% respectively. Mortality on transplant was 1.3%, one of the lowest values registered so far. Mortality on renal replacement therapy was around 5% among patients from 45 to 64 years, 11% between 65 and 74 years and 19% among the patients older than 75 years.

Role of pulse pressure on cardiovascular risk in chronic kidney disease patients.

Epidemiologic studies have emphasized the close relationship between high BP and cardiovascular disease (CVD). Recently published prospective studies have focus on systolic and pulse pressure (PP). Systolic BP seems to be a more important factor than diastolic BP on cardiovascular and all-cause mortality in older patients. PP reflects stiffness of the large arteries and increases with age. Increasingly, PP is recognized as an independent predictor of myocardial infarction, congestive heart failure, and cardiovascular death, even in hypertensive patients who undergo successful antihypertensive drug therapy, especially in older individuals. Chronic kidney disease (CKD) is a major public health problem. The progression of kidney disease and its associated cardiovascular complications are the major causes of morbidity and mortality. This holds true for all stages of kidney disease, including ESRD that requires renal replacement therapy. Most of the traditional CVD risk factors are highly prevalent in CKD, and several nontraditional factors also are associated with atherosclerosis in CKD. The burden of hypertension is present at all stages of CKD. Several studies have shown that PP is a reliable prognostic factor for mortality and CVD in patients who have CKD and are on hemodialysis and in renal transplant patients. The purpose of this review is to show the importance of PP on cardiovascular risk in patients with CKD, including kidney transplant recipients.

Evolution of tacrolimus blood levels and concentration-dose ratios in patients who develop new onset diabetes mellitus after kidney transplantation.

New onset diabetes mellitus (NODM) affects kidney transplantation outcome. Several risk factors, including immunosuppressive drug levels, are related with NODM development. This analysis evaluates the incidence and risk factors of NODM in kidney transplant patients receiving tacrolimus, taking into account 6-month blood levels and concentration-dose ratios (CDRs). Seventy-six patients under tacrolimus therapy who received a cadaveric renal transplant in our centre and with graft survival higher than 1 year were included in the study. NODM was defined as two fasting plasma glucose values > or =126 mg/dl or symptoms of diabetes plus casual plasma glucose concentrations > or =200 mg/dl throughout the first year. We examined previously reported variables related with NODM development. The incidence of NODM at 12 months was 27.6%. Risk factors for NODM included older age, higher first tacrolimus level, higher body mass index and lower first year weight gain. In multivariate analysis, the first year occurrence of NODM was significantly determined by the first tacrolimus blood level >20 ng/ml and age older than 50 years. CDR remains significantly higher in NODM throughout the 6 months. Older age and a high first tacrolimus blood level are associated with the development of NODM during the first year after kidney transplantation. NODM patients show higher CDR during the first 6 months.

Apolipoprotein C-III and E polymorphisms and cardiovascular syndrome, hyperlipidemia, and insulin resistance in renal transplantation.

Hyperlipidemia and insulin resistance frequently develop after renal transplantation, contributing to cardiovascular disease. Individual differences in response based upon genetic variations in proteins regulating lipidic and glucose tolerance metabolism could be expected. In the general population, the S2 allelic variant of the apoprotein (apo) C-III gene has been associated with hypertriglyceridemia and an insulin resistant state, whereas the E4 allele of the apo E has been associated with hypercholesterolemia and atherosclerosis. Its influence in renal transplant patients remains to be seen. In order to assess the impact of apo E and C-III major polymorphisms on atherosclerotic vascular disease, lipid profile and impaired glucose tolerance in renal transplant patients, we studied 110 consecutively examined patients undergoing kidney transplantation (age range 24-73 years). Atherosclerotic complications were detected in 25% of patients, with age, male sex and hypercholesterolemia being significant atherosclerotic risk factors. Among the male patients with E4 allele, the odds ratio for coronary disease and global atherosclerosis were 10.2 (95% CI) and 6.4 (95% CI), respectively. There were no significant differences in the frequency of any of the polymorphisms among patients with dyslipidemia and impaired glucose tolerance. As the number of patients in our sample was small, larger studies are needed to verify these issues. While in the studied population C-III polymorphism appears to have little association with the prevalence of atherosclerotic complications, E4 allele should be considered as a genetic marker of coronary artery disease and global atherosclerosis in renal transplant patients.

Gastrointestinal disease and the kidney.

Renal disease at any stage, from insufficiency to end-stage renal disease requiring dialysis or following renal transplantation, is often accompanied by significant gastrointestinal (GI) symptoms. Conversely, patients with GI disease may present with significant renal complications. Patients with end-stage renal disease, patients undergoing dialysis, and recipients of renal grafts are at increased risk for GI complications, including erosive disease and GI bleeding. Selection of pharmacotherapy for GI conditions in patients with concomitant renal disease is complicated by three factors: (1) the potential for a significant negative impact on renal function, which is already compromised; (2) the requirement for dosing alteration in renal insufficiency; and (3) the potential for drug-drug interactions with concomitant medications. Proton pump inhibitors appear to be the most suitable acid-suppressing therapy for patients with renal disease; recently developed drugs in this class (e.g. rabeprazole) may be the best choice for treatment of patients with both acid-related GI conditions and renal disease.