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BACKGROUND AND HYPOTHESIS: Despite continuous advancement, treatment of lupus nephritis (LN) remains challenging. Recent guidelines now include a regimen incorporating tacrolimus as a first-line treatment option. Even though tacrolimus is effective in combination with mycophenolate and corticosteroids, concerns remain regarding long-term use, given its association with increased cardiovascular risks including nephrotoxicity, hypertension, dyslipidemia and hyperglycemia in kidney transplant recipients. However, in LN, long-term evaluations and head-to-head comparisons are lacking and thus the safety profile remains ill-defined. We hypothesized that chronic toxicity also occurs in LN patients. Therefore, this study aimed to assess long-term cardiovascular and renal outcomes of tacrolimus in LN patients. METHODS: This observational cohort study examined adult LN patients treated with tacrolimus, assessing renal outcomes, hypertension, diabetes, dyslipidemia, cardiovascular events and the Framingham risk score. The results were compared to a control group of CNI-naïve LN patients. RESULTS: Of the 219 LN patients in this study, 43 (19.6%) had tacrolimus exposure. Over a median follow-up of 7.1 years, tacrolimus use was associated with significant kidney function decline (6.8 ml/min/1.73m2, versus 0.8 in the control group). The incidence of end-stage kidney disease was similar. Cardiovascular event incidence was equally low in both groups. The 10-year risk of coronary heart disease was lower in the tacrolimus group, primarily due to age differences. HbA1c levels were higher in the tacrolimus group (37.4 mmol/mol) than in controls (33.6 mmol/mol), although the incidence of diabetes was similar. There were no differences in the occurrence of hypertension or dyslipidemia. CONCLUSIONS: Our study demonstrated that tacrolimus exposure was associated with long-term kidney function loss in LN patients. Although cardiovascular risk factors and events were similar to patients never exposed to tacrolimus, there may be an increased risk of developing diabetes. Therefore, our study supports vigilance towards renal adverse effects in LN patients treated with tacrolimus.
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BACKGROUND: Chronic kidney disease-associated pruritus (CKD-aP) is common in dialysis patients, and is associated with lower quality of life and increased risk of death. We investigated the association between residual estimated glomerular filtration rate (eGFR), dialysis adequacy or serum phosphate level and CKD-aP in incident dialysis patients. METHODS: A total of 1256 incident hemodialysis (HD) and 670 peritoneal dialysis (PD) patients (>18 years) from the Netherlands Cooperative Study on the Adequacy of Dialysis (NECOSAD) study were included (1997-2007) and followed until death, transplantation or a maximum of 10 years. CKD-aP was measured using a single item of the Kidney Disease Quality of Life Instrument-36. The associations were studied by logistic and linear regression analyses, adjusted for potential baseline confounders. RESULTS: At baseline mean (standard deviation) age was 60 (16) years, 62% were men and median (interquartile range) residual eGFR was 3.4 (1.7; 5.3) mL/min/1.73 m2. The prevalence of CKD-aP (â¼70%) was similar in HD and PD. It was observed that 12 months after starting dialysis (after multivariable adjustment) each 1 mL/min/1.73 m2 higher residual eGFR, one unit higher total weekly Kt/V, or 1 mmol/L lower serum phosphate level was associated with lower burden of CKD-aP in HD and PD patients of -0.05 (95% CI -0.09; -0.02) and -0.09 (95% CI -0.13; -0.05), -0.15 (95% CI -0.26; -0.05) and -0.35 (95% CI -0.54; -0.16), and of -0.34 (95%CI: -0.51; -0.17) and -0.45 (95%CI: -0.71; -0.19), respectively. We found no association between dialysis Kt/V and CKD-aP. CONCLUSIONS: Higher residual eGFR and lower serum phosphate level, but not the dialysis dose, were related with lower burden of CKD-aP in dialysis patients.
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Falência Renal Crônica , Insuficiência Renal Crônica , Masculino , Humanos , Pessoa de Meia-Idade , Feminino , Diálise Renal/efeitos adversos , Qualidade de Vida , Insuficiência Renal Crônica/complicações , Insuficiência Renal Crônica/terapia , Rim , Prurido/epidemiologia , Prurido/etiologia , Fosfatos , Falência Renal Crônica/complicações , Falência Renal Crônica/terapiaRESUMO
BACKGROUND: Health-related quality of life (HRQOL) is an increasingly important patient-reported outcome in kidney transplant recipients (KTRs). This study explored relationships between symptom prevalence and burden with HRQOL, and age and gender differences in symptom experience. METHODS: Eligible Dutch KTRs transplanted in Leiden University Medical Center were invited for this cross-sectional study. HRQOL, and occurrence and burden of 62 symptoms were measured using validated questionnaires. Univariate and multivariate regression analysis were used for investigating the associations of symptom experience with mental and physical HRQOL, and differences in symptom experience between genders and KTRs of diverse age groups. RESULTS: A total of 631 KTRs were analyzed; the mean (standard deviation) age was 61.3 (11.3) years, and 62% were male. The median (interquartile range) number of symptoms was 14 (7-22), with a burden of 20 (8-37; range 0-244). Per extra symptom, physical and mental HRQOL decreased [-0.41 (-0.50; -0.31) and -0.51 (-0.59; -0.42), respectively, P < .001]. Most occurring symptoms were bruises, tiredness, lack of energy, urge to urinate at night and dry skin. Sexual problems were considered most burdensome. Female KTRs reported more symptoms than men. Amongst others, younger KTRs experienced more (18-50 > 50-65 ≥65 years) feelings of depression and both female and younger KTRs reported higher symptom prevalence concerning changes in physical appearance. CONCLUSION: KRTs' symptom experience differed depending on gender and age, highlighting the need to develop tailored treatment strategies to reduce symptom experience and subsequently improve HRQOL.
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Transplante de Rim , Qualidade de Vida , Humanos , Masculino , Feminino , Pessoa de Meia-Idade , Estudos Transversais , Transplante de Rim/efeitos adversos , Fatores Sexuais , Análise de Regressão , TransplantadosRESUMO
BACKGROUND: Hospital readmission after transplantation is common in kidney transplant recipients (KTRs). In this study, we aim to compare the risk of 3-month hospital readmission after kidney transplantation with different donor types in the overall population and in both young (< 65 years) and elderly (≥65 years) KTRs. METHODS: We included all first-time adult KTRs from 2016 to 2018 in the Netherlands Organ Transplant Registry. Multivariable logistic regression models were used to estimate the effect while adjusting for baseline confounders. RESULTS: Among 1917 KTRs, 615 (32.1%) had at least one hospital readmission. Living donor kidney transplantation (LDKT) recipients had an adjusted OR of 0.76 (95%CI, 0.61 to 0.96; p = 0.02) for hospital readmission compared to deceased donor kidney transplantation (DDKT) recipients. In the young and elderly, the adjusted ORs were 0.69 (95%CI, 0.52 to 0.90, p = 0.01) and 0.93 (95%CI, 0.62 to 1.39, p = 0.73) and did not differ significantly from each other (p-value for interaction = 0.38). In DDKT, the risk of hospital readmission is similar between recipients with donation after cardiac death (DCD) or brain death (DBD) and the risk was similar between the young and elderly. CONCLUSION: A lower risk of post-transplant 3-month hospital readmission was found in recipients after LDKT compared to DDKT, and this benefit of LDKT might be less dominant in elderly patients. In DDKT, having either DCD or DBD donors is not associated with post-transplant 3-month hospital readmission, regardless of age. Tailored patient management is needed for recipients with DDKT and elderly KTRs.
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Transplante de Rim , Readmissão do Paciente/estatística & dados numéricos , Adolescente , Adulto , Fatores Etários , Idoso , Morte Encefálica , Feminino , Seguimentos , Humanos , Doadores Vivos , Masculino , Pessoa de Meia-Idade , Países Baixos , Sistema de Registros , Adulto JovemRESUMO
Background: The effect of maintenance intravenous (IV) iron administration on subsequent achievement of anemia management goals and mortality among patients recently initiating hemodialysis is unclear. Methods: We performed an observational cohort study, in adult incident dialysis patients starting on hemodialysis. We defined IV administration strategies over a 12-week period following a patient's initiation of hemodialysis; all those receiving IV iron at regular intervals were considered maintenance, and all others were considered non-maintenance. We used multivariable models adjusting for demographics, clinical and treatment parameters, iron dose, measures of iron stores and pro-infectious and pro-inflammatory parameters to compare these strategies. The outcomes under study were patients' (i) achievement of hemoglobin (Hb) of 10-12 g/dL, (ii) more than 25% reduction in mean weekly erythropoietin stimulating agent (ESA) dose and (iii) mortality, ascertained over a period of 4 weeks following the iron administration period. Results: Maintenance IV iron was administered to 4511 patients and non-maintenance iron to 8458 patients. Maintenance IV iron administration was not associated with a higher likelihood of achieving an Hb between 10 and 12 g/dL {adjusted odds ratio (OR) 1.01 [95% confidence interval (CI) 0.93-1.09]} compared with non-maintenance, but was associated with a higher odds of achieving a reduced ESA dose of 25% or more [OR 1.33 (95% CI 1.18-1.49)] and lower mortality [hazard ratio (HR) 0.73 (95% CI 0.62-0.86)]. Conclusions: Maintenance IV iron strategies were associated with reduced ESA utilization and improved early survival but not with the achievement of Hb targets.
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Anemia/tratamento farmacológico , Ferro/uso terapêutico , Diálise Renal , Oligoelementos/uso terapêutico , Administração Intravenosa , Estudos de Coortes , Gerenciamento Clínico , Feminino , Hemoglobinas/análise , Humanos , Masculino , Pessoa de Meia-IdadeRESUMO
The association of residual kidney function (RKF) with improved outcomes in peritoneal dialysis and hemodialysis patients is now widely recognized. RKF provides substantial volume and solute clearance even after dialysis initiation. In particular, RKF provides clearance of nonurea solutes, many of which are potential uremic toxins and not effectively removed by conventional hemodialysis. The presence of RKF provides a distinct advantage to incident dialysis patients and is an opportunity for nephrologists to individualize dialysis treatments tailored to their patients' unique solute, volume, and quality of life needs. The benefits of RKF present the opportunity to personalize the management of uremia.
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Taxa de Filtração Glomerular/fisiologia , Falência Renal Crônica/terapia , Rim/fisiopatologia , Medicina de Precisão/métodos , Diálise Renal , Humanos , Falência Renal Crônica/fisiopatologia , PrognósticoRESUMO
Residual kidney function contributes substantially to solute clearance in dialysis patients but cannot be assessed without urine collection. We used serum filtration markers to develop dialysis-specific equations to estimate urinary urea clearance without the need for urine collection. In our development cohort, we measured 24-hour urine clearances under close supervision in 44 patients and validated these equations in 826 patients from the Netherlands Cooperative Study on the Adequacy of Dialysis. For the development and validation cohorts, median urinary urea clearance was 2.6 and 2.4 ml/min, respectively. During the 24-hour visit in the development cohort, serum ß-trace protein concentrations remained in steady state but concentrations of all other markers increased. In the validation cohort, bias (median measured minus estimated clearance) was low for all equations. Precision was significantly better for ß-trace protein and ß2-microglobulin equations and the accuracy was significantly greater for ß-trace protein, ß2-microglobulin, and cystatin C equations, compared with the urea plus creatinine equation. Area under the receiver operator characteristic curve for detecting measured urinary urea clearance by equation-estimated urinary urea clearance (both 2 ml/min or more) were 0.821, 0.850, and 0.796 for ß-trace protein, ß2-microglobulin, and cystatin C equations, respectively; significantly greater than the 0.663 for the urea plus creatinine equation. Thus, residual renal function can be estimated in dialysis patients without urine collections.
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Biomarcadores/sangue , Taxa de Filtração Glomerular , Nefropatias/terapia , Rim/fisiopatologia , Diálise Peritoneal , Diálise Renal , Adulto , Idoso , Área Sob a Curva , Baltimore , Biomarcadores/urina , Creatinina/sangue , Estudos Transversais , Cistatina C/sangue , Feminino , Humanos , Oxirredutases Intramoleculares/sangue , Nefropatias/sangue , Nefropatias/diagnóstico , Nefropatias/fisiopatologia , Lipocalinas/sangue , Masculino , Pessoa de Meia-Idade , Modelos Biológicos , Países Baixos , Valor Preditivo dos Testes , Estudos Prospectivos , Curva ROC , Reprodutibilidade dos Testes , Ureia/sangue , Ureia/urina , Microglobulina beta-2/sangueRESUMO
BACKGROUND: Intravenous iron use in hemodialysis patients has greatly increased over the last decade, despite limited studies on the safety of iron. METHODS: We studied the association of receipt of intravenous iron with hospitalizations in an incident cohort of hemodialysis patients. We examined 9544 patients from Dialysis Clinic, Inc. (DCI). We ascertained intravenous iron use from DCI electronic medical record and USRDS data files, and hospitalizations through Medicare claims. We examined the association between iron exposure accumulated over 1-, 3- or 6-month time windows and incident hospitalizations in the follow-up period using marginal structural models accounting for time-dependent confounders. We performed sensitivity analyses including recurrent events models for multiple hospitalizations and models for combined outcome of hospitalization and death. RESULTS: There were 22 347 hospitalizations during a median follow-up of 23 months. Higher cumulative dose of intravenous iron was not associated with all-cause, cardiovascular or infectious hospitalizations [HR 0.97 (95% CI: 0.77-1.22) for all-cause hospitalizations comparing >2100 mg versus 0-900 mg of iron over 6 months]. Findings were similar in models examining the risk of hospitalizations in 1- and 3-month windows [HR 0.88 (95% CI: 0.79-0.99) and HR 0.88 (95% CI: 0.74-1.03), respectively] or the risk of combined outcome of hospitalization and death in the 6-month window [HR 0.98 (95% CI: 0.78-1.23)]. CONCLUSIONS: Higher cumulative dose of intravenous iron may not be associated with increased risk of hospitalizations in hemodialysis patients. While clinical trials are needed, employing higher iron doses to reduce erythropoiesis-stimulating agents does not appear to increase morbidity in routine clinical care.
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Doenças Cardiovasculares/diagnóstico , Hospitalização/estatística & dados numéricos , Compostos de Ferro/administração & dosagem , Falência Renal Crônica/complicações , Diálise Renal , Administração Intravenosa , Idoso , Doenças Cardiovasculares/etiologia , Causas de Morte , Bases de Dados Factuais , Feminino , Humanos , Falência Renal Crônica/tratamento farmacológico , Masculino , Pessoa de Meia-Idade , Fatores de RiscoRESUMO
BP variability (BPV) is an important predictor of outcomes in the general population, but its association with clinical outcomes in hemodialysis patients is not clear. We identified 11,291 patients starting dialysis in 2003-2008 and followed them through December 31, 2008 (median=22 months). Predialysis systolic BPV was assessed over monthly intervals. Outcomes included factors associated with BPV, mortality (all-cause and cardiovascular), and first cardiovascular event (cardiovascular death or hospitalization). Patients' mean age was 62 years, 55% of patients were men, and 58% of patients were white. Modifiable factors associated with higher BPV included obesity, higher calcium-phosphate product levels, and lower hemoglobin concentration; factors associated with lower BPV included greater fluid removal, achievement of prescribed dry weight during dialysis, higher hemoglobin concentration, and antihypertensive regimens without ß-blockers or renin-angiotensin system blocking agents. In total, 3200 deaths occurred, including 1592 cardiovascular deaths. After adjustment for demographics, comorbidities, and clinical factors, higher predialysis BPV was associated with increased risk of all-cause mortality (hazard ratio [HR], 1.18; 95% confidence interval [95% CI] per 1 SD increase in BPV, 1.13 to 1.22), cardiovascular mortality (HR, 1.18; 95% CI, 1.12 to 1.24), and first cardiovascular event (HR, 1.11; 95% CI, 1.07 to 1.15). Results were similar when BPV was categorized in tertiles and patients were stratified by baseline systolic BP. In summary, predialysis systolic BPV is an important, potentially modifiable risk factor for death and cardiovascular outcomes in incident hemodialysis patients. Studies of BP management in dialysis patients should focus on both absolute BP and BPV.
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Diálise Renal , Sístole , Antagonistas Adrenérgicos beta/uso terapêutico , Adulto , Idoso , Doenças Cardiovasculares/mortalidade , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Diálise Renal/mortalidade , Sístole/efeitos dos fármacos , Resultado do TratamentoRESUMO
The estimated glomerular filtration rate (eGFR) at dialysis initiation has been rising. Observational studies suggest harm, but may be confounded by unmeasured factors. As instrumental variable methods may be less biased, we performed a retrospective cohort study of 310,932 patients who started dialysis between 2006 and 2008 and were registered in the United States Renal Data System in order to describe geographic variation in eGFR at dialysis initiation and determine its association with mortality. Patients were grouped into 804 health service areas (HSAs) by zip code. Individual eGFR at dialysis initiation averaged 10.8 ml/min per 1.73 m(2) but varied geographically. Only 11% of the variation in mean HSA-level eGFR at dialysis initiation was accounted for by patient characteristics. We calculated demographic-adjusted mean eGFR at dialysis initiation in the HSAs using the 2006 and 2007 incident cohort as our instrument and estimated the association between individual eGFR at dialysis initiation and mortality in the 2008 incident cohort using the two-stage residual inclusion method. Among 89,547 patients starting dialysis in 2008 with eGFR 5-20 ml/min per 1.73 m(2), eGFR at initiation was not associated with mortality over a median of 15.5 months (hazard ratio, 1.025 per 1 ml/min per 1.73 m(2) for eGFR 5-14 ml/min per 1.73 m(2); and 0.973 per 1 ml/min per 1.73 m(2) for eGFR 14-20 ml/min per 1.73 m(2)). Thus, there was no associated harm or benefit with early dialysis initiation in the United States.
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Área Programática de Saúde/estatística & dados numéricos , Intervenção Médica Precoce , Diálise Renal/estatística & dados numéricos , Insuficiência Renal Crônica/mortalidade , Insuficiência Renal Crônica/terapia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Bases de Dados Factuais , Feminino , Taxa de Filtração Glomerular , Humanos , Masculino , Pessoa de Meia-Idade , Sistema de Registros , Diálise Renal/efeitos adversos , Diálise Renal/tendências , Insuficiência Renal Crônica/fisiopatologia , Estudos Retrospectivos , Estatística como Assunto , Fatores de Tempo , Estados Unidos/epidemiologia , Adulto JovemRESUMO
BACKGROUND: Previous observational studies examining outcomes associated with the timing of dialysis therapy initiation in the United States have often been limited by lead time and survivor bias. STUDY DESIGN: Retrospective cohort study comparing the effectiveness of early versus later (conventional) dialysis therapy initiation in advanced chronic kidney disease (CKD). The analysis used inverse probability weighting to account for an individual's contribution to different exposure groups over time in a pooled logistic regression model. Patients contributed risk to both exposure categories (early and later initiation) until there was a clear treatment strategy (ie, dialysis therapy was initiated early or estimated glomerular filtration rate [eGFR] decreased to <10mL/min/1.73m(2)). SETTING & PARTICIPANTS: Patients with CKD who had at least one face-to-face outpatient encounter with a Cleveland Clinic health care provider as of January 1, 2005, and at least 3 eGFRs in the range of 20-30mL/min/1.73m(2) measured at least 180 days apart. PREDICTORS: Timing of dialysis therapy initiation as determined using model-based interpolation of eGFR trajectories over time. Timing was defined as early (interpolated eGFR at dialysis therapy initiation≥10mL/min/1.73m(2)) or later (eGFR < 10mL/min/1.73m(2)) and was time-varying. OUTCOMES: Death from any cause occurring from the time that eGFR was equal to 20mL/min/1.73m(2) through September 15, 2009. RESULTS: The study population consisted of 652 patients meeting inclusion criteria. Most (71.3%) of the study population did not initiate dialysis therapy during follow-up. Patients who did not initiate dialysis therapy (n=465) were older, more likely to be white, and had more favorable laboratory profiles than those who started dialysis therapy. Overall, 146 initiated dialysis early and 80 had eGFRs decrease to <10mL/min/1.73m(2). Many participants (n=426) were censored prior to attaining a clear treatment strategy and were considered undeclared. There was no statistically significant survival difference for the early compared with later initiation strategy (OR, 0.85; 95% CI, 0.65-1.11). LIMITATIONS: Interpolated eGFR, moderate sample size, and likely unmeasured confounders. CONCLUSIONS: In patients with advanced CKD, timing of dialysis therapy initiation was not associated with mortality when accounting for lead time bias and survivor bias.
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Diálise Renal/métodos , Insuficiência Renal Crônica/terapia , Idoso , Progressão da Doença , Feminino , Seguimentos , Taxa de Filtração Glomerular , Humanos , Masculino , Pessoa de Meia-Idade , Insuficiência Renal Crônica/mortalidade , Insuficiência Renal Crônica/fisiopatologia , Estudos Retrospectivos , Taxa de Sobrevida/tendências , Fatores de Tempo , Resultado do Tratamento , Estados Unidos/epidemiologiaRESUMO
BACKGROUND: Several observational studies have evaluated the effect of a single exposure window with blood pressure (BP) medications on outcomes in incident dialysis patients, but whether BP medication prescription patterns remain stable or a single exposure window design is adequate to evaluate effect on outcomes is unclear. METHODS: We described patterns of BP medication prescription over 6 months after dialysis initiation in hemodialysis and peritoneal dialysis patients, stratified by cardiovascular comorbidity, diabetes, and other patient characteristics. The cohort included 13,072 adult patients (12,159 hemodialysis, 913 peritoneal dialysis) who initiated dialysis in Dialysis Clinic, Inc., facilities January 1, 2003-June 30, 2008, and remained on the original modality for at least 6 months. We evaluated monthly patterns in BP medication prescription over 6 months and at 12 and 24 months after initiation. RESULTS: Prescription patterns varied by dialysis modality over the first 6 months; substantial proportions of patients with prescriptions for beta-blockers, renin angiotensin system agents, and dihydropyridine calcium channel blockers in month 6 no longer had prescriptions for these medications by month 24. Prescription of specific medication classes varied by comorbidity, race/ethnicity, and age, but little by sex. The mean number of medications was 2.5 at month 6 in hemodialysis and peritoneal dialysis cohorts. CONCLUSIONS: This study evaluates BP medication patterns in both hemodialysis and peritoneal dialysis patients over the first 6 months of dialysis. Our findings highlight the challenges of assessing comparative effectiveness of a single BP medication class in dialysis patients. Longitudinal designs should be used to account for changes in BP medication management over time, and designs that incorporate common combinations should be considered.
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Anti-Hipertensivos/uso terapêutico , Hipertensão/tratamento farmacológico , Hipertensão/epidemiologia , Prescrições/estatística & dados numéricos , Diálise Renal/estatística & dados numéricos , Insuficiência Renal Crônica/epidemiologia , Insuficiência Renal Crônica/reabilitação , Anti-Hipertensivos/classificação , Causalidade , Comorbidade , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Padrões de Prática Médica/estatística & dados numéricos , Prevalência , Fatores de Risco , Taxa de Sobrevida , Resultado do Tratamento , Estados Unidos/epidemiologiaRESUMO
Background: Depressive symptoms are associated with adverse clinical outcomes in patients with end-stage kidney disease; however, few small studies have examined this association in patients with earlier phases of chronic kidney disease (CKD). We studied associations between baseline depressive symptoms and clinical outcomes in older patients with advanced CKD and examined whether these associations differed depending on sex. Methods: CKD patients (≥65 years; estimated glomerular filtration rate ≤20 mL/min/1.73 m2) were included from a European multicentre prospective cohort between 2012 and 2019. Depressive symptoms were measured by the five-item Mental Health Inventory (cut-off ≤70; 0-100 scale). Cox proportional hazard analysis was used to study associations between depressive symptoms and time to dialysis initiation, all-cause mortality and these outcomes combined. A joint model was used to study the association between depressive symptoms and kidney function over time. Analyses were adjusted for potential baseline confounders. Results: Overall kidney function decline in 1326 patients was -0.12 mL/min/1.73 m2/month. A total of 515 patients showed depressive symptoms. No significant association was found between depressive symptoms and kidney function over time (P = 0.08). Unlike women, men with depressive symptoms had an increased mortality rate compared with those without symptoms [adjusted hazard ratio 1.41 (95% confidence interval 1.03-1.93)]. Depressive symptoms were not significantly associated with a higher hazard of dialysis initiation, or with the combined outcome (i.e. dialysis initiation and all-cause mortality). Conclusions: There was no significant association between depressive symptoms at baseline and decline in kidney function over time in older patients with advanced CKD. Depressive symptoms at baseline were associated with a higher mortality rate in men.
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BACKGROUND: The Modification of Diet in Renal Disease (MDRD) equation is widely used for the estimation of glomerular filtration rate (GFR) from plasma creatinine. It has been well validated in patients with various degrees of impaired kidney function, but not in patients with end-stage renal disease (ESRD). Plasma creatinine is determined by GFR and muscle mass. Importance of the latter may increase at low GFR. Our aim was to firstly compare estimated GFR (eGFR by MDRD equation) with measured GFR (mGFR, mean of creatinine and urea clearance) just before the start of dialysis. Secondly, the relationship of eGFR and mGFR with mortality and muscle mass was analysed. METHODS: ESRD patients with 24-h urine collections and a plasma sample available at the start of dialysis [n = 569, 61% male, mean (standard deviation) age 58 (15) years] were selected from the Netherlands Cooperative Study on the Adequacy of Dialysis. Incident dialysis patients were followed until death, transplantation or end of study. RESULTS: mGFR was 6.0 (2.6) and eGFR was 6.8 (2.4) mL/min/1.73 m(2). Although eGFR overestimated mGFR with only 0.8 mL/min/1.73 m(2), limits of agreement ranged from - 4.1 to + 5.6 mL/min/1.73 m(2). The highest eGFR values were associated with the highest mortality rates [adjusted hazard ratio 1.4 (1.0, 1.9)]. eGFR but not mGFR was associated with muscle mass (P = 0.001). CONCLUSIONS: These data imply that estimation of GFR by equations using plasma creatinine in the denominator cannot be used for this purpose in patients with ESRD because the effect of GFR on plasma creatinine is overruled by that of muscle mass.
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Algoritmos , Dieta , Taxa de Filtração Glomerular , Falência Renal Crônica/mortalidade , Falência Renal Crônica/fisiopatologia , Músculo Esquelético/fisiologia , Creatinina/sangue , Feminino , Seguimentos , Humanos , Falência Renal Crônica/terapia , Modelos Lineares , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Terapia de Substituição Renal , Taxa de SobrevidaRESUMO
BACKGROUND: Progressive renal insufficiency is frequent in heart failure patients with a left ventricular assist device (LVAD). The optimal strategy for long-term dialysis in LVAD patients and its effect on quality-of-life in these patients remain to be determined. CASE SUMMARY: Our 55-year-old patient with pre-existing renal insufficiency received an LVAD as destination therapy because of advanced ischaemic heart failure. Six years after implantation, he developed end-stage renal disease for which peritoneal dialysis (PD) was initiated. Left ventricular assist device flow alterations during ultrafiltration did not cause clinical or technical problems. The patient's exercise capacity increased and quality-of-life improved. Over 7.5 years after LVAD implantation and 16 months after PD initiation, he died from encephalitis. DISCUSSION: Despite initial improvement, renal function often gradually decreases after LVAD implantation. Data on long-term renal replacement therapy in LVAD patients are limited. Haemodialysis is most commonly applied. Conceptually, however, PD has advantages over haemodialysis including less bloodstream infections, less haemodynamic shifts, and the comfort of the ambulant setting. This case illustrates that PD in an LVAD patient is feasible and improves quality-of-life. Key factors contributing to successful PD in LVAD patients may be a good right ventricular function and close cardiology-nephrology collaboration.
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RATIONALE & OBJECTIVE: Measurement of residual kidney function is recommended for the adjustment of the dialysis prescription, but timed urine collections are difficult and prone to errors. Equations to calculate residual kidney function from serum concentrations of endogenous filtration markers and demographic parameters would simplify monitoring of residual kidney function. However, few equations to estimate residual kidney function using serum concentrations of small solutes and low-molecular-weight proteins have been developed and externally validated. STUDY DESIGN: Study of diagnostic test accuracy. SETTING & PARTICIPANTS: 823 Chinese peritoneal dialysis (PD) patients (development cohort) and 826 PD and hemodialysis patients from the Netherlands NECOSAD study (validation cohort). TESTS COMPARED: Equations to estimate residual kidney function (estimated clearance [eCl]) using serum creatinine, urea nitrogen, cystatin C, ß2-microglobulin (B2M), ß-trace protein (BTP), and combinations, as well as demographic variables (age, sex, height, and weight). Equations were developed using multivariable linear regression analysis in the development cohort and then tested in the validation cohort. Equations were compared with published validated equations. OUTCOMES: Residual kidney function measured as urinary clearance (mCl) of urea nitrogen (mClUN) and average of creatinine and urea nitrogen clearance (mClUN-cr). RESULTS: In external validation, bias (difference between mCl and eCl) was within ± 1.0 unit for all equations. Accuracy (percent of differences within ± 2.0 units) was significantly better for eClBTP, eClB2M, and eClBTP-B2M than eClUN-cr for both mClUN (78%, 80%, and 81% vs 72%; P < 0.05 for all) and mClUN-cr (72%, 78%, and 79% vs 68%; P < 0.05 for all). The area under the curve for predicting mClUN > 2.0 mL/min was highest for eClB2M (0.853) and eClBTP-B2M (0.848). Results were similar for other validated equations. LIMITATIONS: Development cohort only consisted of PD patients, no gold-standard method for residual kidney function measurement. CONCLUSIONS: These results confirm the validity and extend the generalizability of residual kidney function estimating equations from serum concentrations of low-molecular-weight proteins without urine collection.
RESUMO
Antihypertensive medications are commonly prescribed to hemodialysis patients but the optimal regimens to prevent morbidity and mortality are unknown. The goal of our study was to compare the association of routinely prescribed antihypertensive regimens with outcomes in US hemodialysis patients.We used 2 datasets for our analysis. Our primary cohort (US Renal Data System [USRDS]) included adult patients initiating in-center hemodialysis from July 1, 2006 to June 30, 2008 (nâ=â33,005) with follow-up through December 31, 2009. Our secondary cohort included adult patients from Dialysis Clinic, Inc. (DCI), a national not-for-profit dialysis provider, initiating in-center hemodialysis from January 1, 2003 to June 30, 2008 (nâ=â11,291) with follow-up through December 31, 2008. We linked the USRDS cohort with Medicare part D prescriptions-fill data and the DCI cohort with USRDS data. Unique aspect of USRDS cohort was pharmacy prescription-fill data and for DCI cohort was detailed clinical data, including blood pressure, weight, and ultrafiltration. We classified prescribed antihypertensives into the following mutually exclusive regimens: ß-blockers, renin-angiotensin system blocking drugs-containing regimens without a ß-blocker (RAS), ß-blockerâ+âRAS, and others. We used marginal structural models accounting for time-updated comorbidities to quantify each regimen's association with mortality (both cohorts) and cardiovascular hospitalization (DCI-Medicare Subcohort).In the USRDS and DCI cohorts there were 9655 (29%) and 3200 (28%) deaths, respectively. In both cohorts, RAS compared to ß-blockers regimens were associated with lower risk of death; (hazard ratio [HR]) (95% confidence interval [CI]) for all-cause mortality, (0.90 [0.82-0.97] in USRDS and 0.87 [0.76-0.98] in DCI) and cardiovascular mortality (0.84 [0.75-0.95] in USRDS and 0.88 [0.71-1.07] in DCI). There was no association between antihypertensive regimens and the risk of cardiovascular hospitalizations.In hemodialysis patients undergoing routine care, renin-angiotensin system blocking drugs-containing regimens were associated with a lower risk of death compared with ß-blockers-containing regimens but there was no association with cardiovascular hospitalizations. Pragmatic clinical trials are needed to specifically examine the effectiveness of these commonly used antihypertensive regimens in dialysis patients.
Assuntos
Anti-Hipertensivos/uso terapêutico , Hospitalização/estatística & dados numéricos , Hipertensão/tratamento farmacológico , Falência Renal Crônica/mortalidade , Diálise Renal/mortalidade , Antagonistas Adrenérgicos beta/uso terapêutico , Idoso , Bloqueadores do Receptor Tipo 2 de Angiotensina II/uso terapêutico , Inibidores da Enzima Conversora de Angiotensina/uso terapêutico , Anti-Hipertensivos/administração & dosagem , Doenças Cardiovasculares/mortalidade , Comorbidade , Feminino , Humanos , Hipertensão/epidemiologia , Falência Renal Crônica/epidemiologia , Falência Renal Crônica/terapia , Masculino , Pessoa de Meia-IdadeRESUMO
BACKGROUND: Ultrafiltration failure is an important complication of long-term peritoneal dialysis (PD). A high effective lymphatic absorption rate (ELAR) can contribute to impaired ultrafiltration. It is unknown whether the ELAR increases with time on PD. OBJECTIVE: The relationship between the ELAR and duration of PD was analyzed, as well as the correlation between the ELAR and other transport parameters. We also studied the relation between the ELAR and cancer antigen 125 (CA125) a marker for mesothelial cell mass. SETTING: Peritoneal dialysis unit in the Academic Medical Center, Amsterdam. DESIGN: Cross-sectional and longitudinal studies of standard peritoneal permeability analyses (SPAs; 4-hour dwells, dextran 70 as a volume marker) with glucose 3.86% in 130 PD patients. METHODS: SPAs were analyzed in 130 stable PD patients (77 males). Median duration of PD was 25 months (range 1-214) in a cross-sectional study. The last SPA from each patient was analyzed. The longitudinal analysis included 24 patients (12 males) from whom at least 3 SPAs were available with a minimum interval of 8 months. Dextran 70, 1 g/L, was administered intraperitoneally at the initiation of the test. Lymphatic absorption was calculated from the disappearance rate of dextran 70 during the 4-hour dwell. Therefore, the ELAR included both transmesothelial and subdiaphragmatic uptake of dextran 70. RESULTS: Median ELAR was 1.43 mL/minute (range 0.17- 6.59 mL/minute). No relationship was found between the ELAR and duration of PD in the cross-sectional analysis, nor was there a trend in time for 20 of the 24 patients studied longitudinally. In 4 patients, a negative trend was found. None of these had ultrafiltration failure and all 4 patients had a different cause for end-stage renal failure. The ELAR was correlated with parameters of peritoneal solute transport, but not with CA125 when investigated in a cross-sectional analysis. Only after 48 months of PD treatment was a significant relationship between the ELAR and CA125 seen (r = 0.46, p < 0.05). CONCLUSIONS: No time trend is present for the effective peritoneal lymphatic absorption rate, and it is not associated with patient or technique survival. Although increased lymphatic absorption is one of the causes of ultrafiltration failure, it is unlikely to contribute to the development of ultrafiltration failure in long-term PD patients with well-maintained transcapillary ultrafiltration.