Compliance with mineral metabolism targets in haemodialysis patients: moving backwards?

BACKGROUND: To standardize therapy and improve the clinical outcome for chronic haemodialysis (HD) patients, guidelines have been developed for mineral metabolism management. We evaluated compliance with different mineral metabolism guidelines. METHODS: 2,951 chronic HD patients from 61 dialysis centres in Spain were studied. Mineral metabolism management data from a 1-year period were analysed according to KDOQI, KDIGO, and Spanish guidelines. RESULTS: Only 1% (KDOQI), 6% (KDIGO) and 11% (Spanish guidelines) of patients continuously achieved total calcium (Ca), phosphate (P) and parathyroid hormone (PTH) target-range values during the year with higher percentages if we considered the 1-year average. The yearly Ca, P and iPTH average accomplished Spanish guidelines with different percentage among centres: CA 62-100%, P 59-91%, PTH 61-89%, and 28-77% considering all three targets together. The KDIGO guidelines recommend similar percentages except for P (33-77%). No differences were found related to eKt/V, online haemodiafiltration/HD, weight, body mass index, or dialysis vintage. They were only related to age, blood flow, effective treatment time, and dialysate calcium but without relevant clinical differences. Patients outside the target ranges generated significantly higher treatment costs. CONCLUSIONS: Compliance with mineral metabolism targets in HD patients was poor and showed a wide variation between treatment centres.

The non-casual relation between eosinophilia and thrombotic microangiopathy.

There are only a few cases in the literature that describes the association between hypereosinophilic syndromes and thrombotic microangiopathy (TMA). Here we present the case of a man who suddenly developed a TMA in the context of eosinophilic pneumonia, who recovered successfully with six sessions of plasmapheresis and corticoids. Although the Pathophysiology is unknown, we hypothesize about the prothrombotic effects of the eosinophils. Also we describe a literature review.

Obesity related risk for chronic kidney disease progression and cardiovascular disease after propensity score matching.

INTRODUCTION: Obesity is a major health problem worldwide. It carries a markedly increased risk for multiple diseases such as type 2 diabetes mellitus, hypertension, cardiovascular disease (CVD) and chronic kidney disease (CKD). To complicate an already difficult topic a new subtype of obesity has been defined lately, the metabolically healthy obese. Our study aimed to clarify the association between obesity, metabolic syndrome and kidney disease progression. METHODS: Observational retrospective single centre study including 212 patients with stage 3-4 CKD with no previous history of rapid kidney disease progression. Patients were divided according to BMI status and presence of metabolic syndrome. Anthropometric, clinical and laboratory data were collected to follow-up. Propensity score matching was performed for age, albuminuria and baseline renal function. During follow-up renal and cardiovascular events were recorded. RESULTS: After a mean follow-up of 88.44±36.07 months a total of 18 patients reached the renal outcome in the non-obese group and 21 in the obese group. Differences were not statistically significant (log rank=0.21: p=0.64). Multiple Cox regression analysis showed that obesity was not predictor for worse renal outcomes [HR 1.01, 95% CI 0.45-2.24; p=0.97]. When stratifying the sample according to baseline metabolic syndrome and obesity presence there was no difference in renal survival (log rank=0.852; p=0.35) A total of 48 cardiovascular events were registered: seventeen in the non-obese group and thirty-one in the obese group. Differences in event-free time between both groups were statistically significant (log rank=4.44;p=0.035), especially after four years of follow-up. After stratifying for MS and obesity presence at baseline the event-free time differences where again statistically significant (log rank=16.86;p=0.001), specially for the obese patients with metabolic syndrome. CONCLUSIONS: Obesity has little impact on chronic kidney disease progression despite the presence or absence of metabolic syndrome in a cohort matched for age, baseline renal function and albuminuria. Obesity conferred greater cardiovascular risk when combined with metabolic syndrome.

Chronic kidney disease progression in patients with resistant hypertension subject to 2 therapeutic strategies: Intensification with loop diuretics vs aldosterone antagonists. / Progresión de la enfermedad renal crónica en pacientes con hipertensión resistente sometidos a 2 estrategias terapéuticas: intensificación con diuréticos de asa vs. antagonistas de la aldosterona.

INTRODUCTION: Actualy, there are few data about glomerular filtration rate (eGFR) drop in patients with resistant hypertension and how diferent therapies can modify chronic kidney disease progression (CKD). OBJECTIVE: To evaluate CKD progression in patients with resistant hypertension undergoing 2diferent therapies: treatment with spironolactone or furosemide. METHODS: We included 30 patients (21M, 9W) with a mean age of 66.3±9.1 years, eGFR 55.8±16.5ml/min/1.73 m2, SBP 162.8±8.2 and DBP 90.2±6.2mmHg: 15 patients received spironolactone and 15 furosemide and we followed up them a median of 32 months (28-41). RESULTS: The mean annual eGFR decrease was -2.8±5.4ml/min/1.73 m2. In spironolactone group was -2.1±4.8ml/min/1.73 m2 and in furosemide group was -3.2±5.6ml/min/1.73 m2, P<0.01. In patients received spironolactone, SBP decreased 23±9mmHg and in furosemide group decreased 16±3mmHg, P<.01. DBP decreased 10±8mmHg and 6±2mmHg, respectively (P<.01). Treatment with spironolactone reduced albuminuria from a serum albumin/creatine ratio of 210 (121-385) mg/g to 65 (45-120) mg/g at the end of follow-up, P<.01. There were no significant changes in the albumin/creatinine ratio in the furosemide group. The slower drop in kidney function was associated with lower SBP (P=.04), higher GFR (P=.01), lower albuminuria (P=.01), not diabetes mellitus (P=.01) and treatment with spironolactone (P=.02). Treatment with spironolactone (OR 2.13, IC 1.89-2.29) and lower albuminuria (OR 0.98, CI 0.97-0.99) maintain their independent predictive power in a multivariate model. CONCLUSION: Treatment with spironolactone is more effective reducing BP and albuminuria in patients with resistant hypertension compared with furosemide and it is associated with a slower progression of CKD in the long term follow up.

[Calciphylaxis: fatal complication of cardiometabolic syndrome in patients with end stage kidney disease]. / Calcifilaxis: complicación grave del síndrome cardio-metabólico en pacientes con enfermedad renal crónica terminal (ERCT).

UNLABELLED: Calciphylaxis characterized by schemic skin ulceration due to subcutaneous small arterioles calcification, is a rare disease but usually fatal. Disorders of calcium metabolism and vascular calcifications are common in dialysis patients but calciphylaxis prevalence is low in patients with end stage renal disease. So we proposed other emergent factors implicated in calciphylaxis development. METHODS: We studied retrospective 8 patients who developed calciphylaxis in our service from january 2001 to december 2006. RESULTS: All patients were female with mean age at diagnosis 68.5+/-6.7 years. All patients were receiving hemodialysis therapy and 6 patients had been receiving hemodialysis less than four months. Six patients had diabetes mellitus type II and all patients were obese (BMI >25 kg/m2). All patients had metabolic syndrome (APTIII) with bad control hypertension and 6 (75%) were receiving anticoagulation therapy with warfarin. Patients didn t have severe alterations of calcium metabolism, all had product calcium-phosphorus <55. All patients developed low blood pressure at the beginning of dialysis treatment (98.3+/-22.7/60+/-18,29 mmHg). 7 patients present proximal lesions in fatty regions like abdomen and thighs. Histopathologic examination reveals calcium deposits in arteriole-sized and small vessels with vascular thrombosis. Prognosis was poor, seven patients died secondary to a sepsis originated in infected cutaneous ulcers. CONCLUSIONS: calciphylaxis is a disease with poor prognosis and high mortality, without specific treatment actually. Female gender, obesity associated with diabetes mellitus and cardiometabolic syndrome, anticoagulant therapy with warfarin and low blood pressure associated with hemodialysis therapy, are risk factors to develop calciphylaxis, in absence of severe disorders of calcium metabolism. In these patients is important to avoid hypotension episodes during dialysis, dialysis hypotension appears to be an important risk factor who promotes ischemia of subcutaneous adipose tissue.

[Therapeutic guidelines fulfillment in clinical practice in patients with chronic kidney disease (CKD)]. / Evaluación del cumplimiento de las guías terapéuticas en la práctica clínica en pacientes con enfermedad renal crónica (ERC).

OBJECTIVE: The present study was designed to determine the degree of fulfillment of the therapeutic objectives recommended in the clinical guidelines in patients with chronic kidney disease (CKD) in a nephrology outpatient clinic and the treatment that the patients were receiving to control these objectives. METHODS: A descriptive, cross-sectional study was performed in unselected patients with CKD (stages 1-5) who attended the nephrology outpatient clinic of the Hospital General Universitario Gregorio Marañón for follow up between 1st January and 1st April 2006. RESULTS: Data from 600 patients with a mean age of 62.8 years (56.5% male) were collected. The distribution of patients according to the stage (S) of CKD was as follows: S1: 11.5%, S2: 18%, S3: 36.7%, S4: 27.5% and S5: 6.3%. The target blood pressure (BP) < 130/80 mmHg was reached in 35.5%. The target diastolic blood pressure was controlled in 70%. However, systolic blood pressure increasing significantly with age and the degree of renal failure was controlled only in 42%. Total cholesterol was or=50 mg/l in 64.1% of patients. Triglyceride level was related to renal function (p=0.04). Most of the patients (94%) had hemoglobin (Hb) levels >or=11 g/dl, because of a significant increase in the percentage of patients treated with erythropoiesis-stimulating agents as the degree of renal function is reduced. Target levels of calcium-phosphorus (CaXP) product (<55 mg2/dl 2) were maintained in all the stages at the expense of decreased Ca and increased P in relation to the decrease in glomerular filtrate (p=0.001). Target Ca (8.4-9.5 mg/dl) was reached in 85% of cases (2% of patients in S3, 37% of patients in S4 and 54% in S5 were receiving calcitriol). Phosphorus levels were adequate in 80% of patients, but target levels of parathyroid hormone (PTH) were maintained only in 28.6% of patients in S3 (35-70 pg/ml), 14% of patients in S4 (70-110 pg/ml) and 28% in S-5 (115-300 pg/ml). CONCLUSIONS: Anemia is the best controlled factor of all the factors related to renal function. The degree of control of blood pressure (BP) has improved in recent years. However, it is still poor, particularly the control of systolic blood pressure getting worse with renal failure and age. It is difficult to reach the target PTH, despite adequate levels of Ca and P. Cholesterol levels, unlike triglyceride levels, do not depend on renal function and require an increase in the use and/or doses of cholesterol-lowering drugs.

[Prolonged acute renal failure and severe polyradiculopathy in ethylene glycol intoxication]. / Fracaso renal agudo prolongado y polirradiculopatía severa en paciente intoxicado con etilenglicol.

Ethylene glycol intoxication involves acute renal failure and severe metabolic acidosis. Prolonged renal insufficiency can occur but terminal chronic renal failure has been reported in very few cases. We describe a patient who after ingestion of 920 ml of ethylene glycol developed prolonged acute renal failure needing hemodialysis for 37 days and then he partly recovered renal function. The patient developed a severe sensitive-motor and autonomic polyradiculopathy.

[Renin-angiotensin system in diabetic nephropathy]. / Sistema renina angiotensina en la nefropatía diabética.

The importance of the renin angiotensin system (RAS) in the development and progression of the diabetic nephropathy is confirmed with the recent demonstration that the development of nephropathy in the diabetic patients can be avoided by blockers of the RAS. For that reason, the promotion of preventive programs for the detection of microalbuminuria, from the early phases of the diabetes is needed. Control of blood pressure, of glucose and lipids are needed. If microalbuminuria is present, the administration of a blocker of RAS, even in the presence of normal blood pressure can prevent the progression to diabetic nephropathy. The main objective to prevent the development and progression of nephropathy in the diabetic patients, as well as the cardiovascular risk, is a strict control of the PA.

[Evaluation of efficacy of darbepoetin alfa administered once monthly as treatment of anemia in predialysis patients with chronic kidney disease]. / Evaluación de la eficacia de la darbepoetina alfa subcutánea administrada en dosis única mensual en el tratamiento de la anemia en pacientes con insuficiencia renal crónica prediálisis.

BACKGROUND: Darbepoetin alfa has demonstrated its efficacy when is administered subcutaneously once-weekly and once every 2 weeks as treatment of anemia in patients with chronic kidney disease (CKD). The aim of this study is to assess the efficacy of subcutaneus darbepoetin alfa administered once monthly in patients with progressive CKD who maintained stable levels of Hb treated on once every other week dosing. METHODS: Patients included in the study maintained hemoglobin (Hb) > 11 g/dl and were receiving darbepoetin alfa once every other week during at least 4 months. We studied a frequency interval dose change: once every other week frequency was converted to once monthly at equivalent dose. The study completers were 12 patients over the third month and 7 at the end of one year evaluation period. RESULTS: A statistic significant decrease in Hb and hematocrit (Hto) was observed over the third month, although all patients maintain Hb levels higher than 11 g/dl. At the same time it was appreciated a statistic significant increased on creatinine (Cr) and parathyroid hormone levels (PTH). At the end of one year evaluation period no differences were observed in any of variables. CONCLUSION: Darbepoetin alfa administered once monthly is an efficacious option as treatment of anemia for patientes with CKD. With a dose of 1 mcg/kg/month, all patientes maintain Hb > 11 g/dl.

[Pharmacogenetics of angiotensin system in non diabetic nephropathy]. / Farmacogenética del sistema de la angiotensina en la nefropatía no diabética.

BACKGROUND: Genetic variability could contribute to the response to pharmacological treatment in patients with nephropathy. In albuminuric diabetic patients the renoprotective effect of angiotensin I-converting enzyme (ACE) inhibition should be lower among homozygotes for the deletion allele (DD) compared to II-homozygotes. METHODS: A total of 71 non-diabetic chronic nephropathy patients were treated with losartan (n = 37) or amlodipine (n = 34). Blood pressure and proteinuria were determined before and after the treatment, and changes in the mean values were statistically compared. Patients were genotyped for the ACE-I/D, angiotensin I receptor type 1 (AGTR1)-1166 A/C, and angiotensinogen (AGT)-M235T polymorphims, and the reduction of blood pressure and proteinuria between the different genotypes were compared. RESULTS: The reduction in systolic or diastolic blood pressure was not found to be different between the ACE-I/D or AGT-M/T genotypes in patients treated with losartan or amlodipine. In patients treated with losartan, we found a significantly higher reduction of diastolic blood pressure in AGTR1-AA patients compared to AC patients (p = 0,0024). We did not find differences in proteinuria-reduction between the different genotypes in patients treated with losartan or amlodipine. CONCLUSIONS: Our data show that the effects of losartan and amlodipine on the absolute mean reduction of blood pressure and proteinuria in non-diabetic nephropathy patients are similar between the different ACE or AGT genotypes. Although based on a small number of patients, the AGTR1-AA genotype was associated with a significantly higher reduction in diastolic blood pressure among losartan-treated patients. Additional studies are necessary to refute or confirm this association.

Renal vascular disease in the elderly.

The aging of Western societies is causing a progressive increase in the number of patients over 65 starting dialysis. The EDTA Registry shows that in 1995 this section of the population represented nearly 45% of patients under dialysis, and the percentage is even higher in the USRDS at 48%, 20% of whom are over 75. These changes have not only been quantitative, but have also modified the causes of end-stage renal disease (ESRD). Diabetic nephropathy (DN) and renal vascular disease (RVD) account for more than 50% of all these causes, reaching 66% according to the latest USRDS calculations. According to these numbers, RVD represents 29% of all causes, the incidence varying with the age group, and has become the main cause of ESRD in the elderly (38% of all cases). Until a few years ago, RVD was synonymous with hypertension, but as the population ages, the range of diseases in this group is increasing. The main RVDs that cause ESRD in the elderly are: hypertensive RVD (nephrosclerosis), atheromatous RVD (either as ischemic atherosclerotic nephropathy or as atheroembolism), and acute occlusion of renal arteries (either bilateral or unilateral in single-kidney patients). The diagnosis of nephrosclerosis in the absence of histological confirmation is a presumed clinical diagnosis, made in most cases by exclusion, and is therefore clearly overestimated. On the other hand, atheromatous RVD is an underdiagnosed disease that is often overlooked. The prevalence, natural history, diagnosis and prognosis are discussed in this report.

Effects of antihypertensive therapy on progression of diabetic nephropathy.

There is a clear relationship between hypertension and the microvascular complications of diabetes. Genetic predisposition to hypertension has been correlated to the risk of diabetic nephropathy in type I diabetes, and hypertension is a well known risk factor for developing nephropathy in patients with type II diabetes. Multiple studies have emphasized the importance of hypertension on renal disease progression, and blood pressure control with conventional antihypertensive drugs slows the rate of renal function loss in diabetic nephropathy. Furthermore, evidence of the role of renin-angiotensin system (RAS) on progression of renal damage has focused much interest on the therapeutic action of the RAS blockade. In patients with type I diabetes, blocking the RAS with angiotensin converting enzyme (ACE) inhibitors prevents progression from microalbuminuria to overt nephropathy, and in overt nephropathy decreases the gradual loss of renal function beyond its blood pressure lowering effect. Less clinical information is available in type II diabetic nephropathy, but our experience and some recent studies suggest that ACE inhibitors also have a renoprotective action in type II diabetes. The role of calcium channel blockers in diabetic nephropathy is not clear. Several short-term studies with the first generation dihydropyridine calcium antagonists showed a lower effect on urinary albumin excretion and a more rapid progression to renal failure than with ACE inhibitors. However, other calcium channel blockers, particularly of the non-dihydropyridine type, have been shown to have a beneficial effect on diabetic nephropathy, decreasing proteinuria and slowing progression.

[Renal and cardiovascular protection associated to antihypertensive treatment in the elderly]. / Protección cardiovascular y renal asociada al tratamiento antihipertensivo en el anciano.

The incidence of arterial hypertension increases with age in such a way that by the age of 60 the incidence is greater than 50% in men and women. This increase is particularly relevant if we consider the changes in systolic blood pressure (increase) and diastolic blood pressure (decrease) in relation to age and as a consequence in the reduction of vascular compliance which is common in men and women over the age of 60. These disorders are associated to artheriosclerosis and the corresponding increase in pulse pressure. It is for these reasons that the most common form of hypertension is isolated systolic hypertension (SBP > 140 mmHg and SBP < 90 mmHg), which represents 50% of hypertensive patients in the elderly population. Isolated systolic hypertension is also associated to an increase in cardiovascular disease (MI, stroke), increasing the risk of mortality four times. In elderly people, hypertension and isolated systolic hypertension are risk factors that can be managed. Today there is sufficient evidence from clinical trials that show a clear benefit in the reduction of the cardiovascular and renal risk associated to the antihypertensive treatment in the elderly, at least when the blood pressure is greater than 160/90 mmHg. The target blood pressure figures to control in the elderly person, probably below 160/90 mmHg, still need to be determined.

[Metabolic syndrome in patients with essential hypertension]. / Síndrome metabólico en pacientes hipertensos esenciales.

We have studied 218 patients with Essential Hypertension. The aim of this study was to determine the prevalence of Metabolic Syndrome (MS) and Insulin resistance (IR) in hypertensive patients and to know the vascular risk associated with MS. Blood pressure (BP), body mass index (BMI), plasma insulin and serum lipids were measured. Plasma glucose was measured basal and after two hours of an oral load of 75 g. Vascular damage was evaluated by measurement of thickening of Intimal/Media complex (TI/MC) in carotid artery by ecco doppler ultrasonography and by the presence of microalbuminuria. IR was estimated by the calculation of the HOMA index of IR. A prevalence of MS of 62% was found and MS was statistically significant associated to vascular damage (p = 0.000). Fifty seven percent of the hypertensive patients who had MS had hypertrigliceridemia which was also related to vascular damage. The prevalence of microalbuminuria (MA) in this population of hypertensive patients was 28% and the presence of MA was significantly associated to (TI/MC) (p = 0000). The hypertensive patients who had vascular damage (a pathological value of TI/MC and or MA) were more frequently males with higher BP, higher BMI (30.45 +/- 4 vs 28.9 +/- 4.3 p = 0.014), more elevated plasma insulin levels (37.38 +/- 22 vs 24.86 +/- 12 p = 0.000) and higher triglyceride levels (2.33 +/- 1.29 vs 1.93 +/- 1.08 p = 0.019). IR was found in 75% of the patients. In a multivariate logistic analysis the independent variables that define vascular damage in hypertensive patients were: Age (p = 0.05), male sex (p = 0.01), Systolic BP (p = 0.002) and IR (p = 0.001). In conclusion, MS is a frequent finding in hypertensive patients. The presence of MS of any of their components increase the vascular risk (TI/MC of carotid artery and microalbuminuria). IR is a common finding in these patients and appears to be one of the most important markers of vascular risk.

High-sensitivity troponin T levels in kidney transplant recipients.

Cardiovascular disease (CVD) is still the leading cause of death among kidney transplant recipients. Validated biomarkers are important to identify patients at high risk for cardiovascular events and mortality. Cardiac troponins are one of the best available prognostic markers in this clinical situation, especially in chronic kidney disease and kidney transplant (KT) patients. The recently appeared high-sensitivity immunoassay to measure troponin T (hsTnT) has not yet been widely studied in the transplant population. We designed a cross-sectional study to evaluate hsTnT levels among 177 stable, asymptomatic patients, including 44.1% (78) males of overall mean age of 56.14 ± 14.25 years. Mean glomerular filtration rate estimated with the MDRD-4 (eGFR MDRD) formula was 48.93 ± 26.46 mL/min/1.73 m(2). Median hsTnT was 11 (interquartile range = 11-26) ng/L. Patients were classified according to their hsTnT levels: normal, below 14 ng/L (57.6%, n = 102 patients), and those with basally elevated levels. Upon univariate analysis, a significant association was found between higher hsTnT levels and several variables, including clinical features, such as age, sex or prior CVD; renal function indicators: creatinine, eGFR MDRD, and proteinuria; nutritional and inflammation markers: albumin, ferritin, and C-reactive protein; and several cardiac enzymes: creatine kinase myocardial band (CKMB), B-type natriuretic peptide, and its N-terminal fragment. A logistic regression model adjusted for age, sex, and variables significantly associated with higher hsTnT levels, showed that male gender, age, CKMB, and lower glomerular filtration rate to show independent relation to basally elevated levels of hsTnT among asymptomatic kidney transplant recipients.