No Race-Ethnicity Adjustment in CKD-EPI Equations Is Required for Estimating Glomerular Filtration Rate in the Brazilian Population.

BACKGROUND: Glomerular filtration rate (GFR) is usually estimated from equations using serum creatinine (sCr), with adjustment for gender, age, and race (black or nonblack). The Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) is the preferred equation for adults, but it was validated for the United States population. We intended to evaluate if the race-ethnicity adjustment proposed for the sCr-based CKD-EPI equations is appropriate for the Brazilian population. METHODS: CKD outpatients had blood samples collected for determination of sCr and serum cystatin C (sCys) levels. GFR was measured (mGFR) by plasma clearance of 51Cr-EDTA and used as the reference. We compared values of mGFR and estimated GFR (eGFR) by CKD-EPI equations based on sCr (eGFRCr) and on the combination of sCr and sCys (eGFRCr-Cys). For African Brazilian patients, eGFR was calculated either without or with race adjustment. Accuracy was considered acceptable if the difference between the values of eGFR and mGFR was ≤30% (P30). RESULTS: 100 patients were enrolled (58 ± 14 years, 46% male, 39% white and 61% African Brazilian). Mean mGFR was 46.7 ± 29.2 ml/min/1.73 m2. Mean eGFRCr and eGFRCr-Cys without race adjustment were 47.8 ± 30.1 ml/min/1.73 m2 and 46.4 ± 30.3 ml/min/1.73 m2, respectively. The corresponding P30 accuracy values were 79.0% and 83.0%. In the African Brazilian subgroup, values for mean mGFR and eGFRCr either without or with race adjustment were 49.8 ± 32.2 ml/min/1.73 m2, 50.4 ± 32.7 ml/min/1.73 m2, and 58.4 ± 37.9 ml/min/1.73 m2 (P < 0.001 vs. mGFR), respectively. P30 accuracy values for eGFRCr either without or with race adjustment were 75.4% and 67.2%, respectively. CONCLUSIONS: The use of CKD-EPI equations without race-ethnicity adjustment seems more appropriate for the Brazilian population.

Tenofovir monotherapy for hepatitis B after 1 year does not produce renal dysfunction, but is associated with hyperparathyroidism not related to vitamin D.

INTRODUCTION: Viral hepatitis B (VHB) represents a major public health problem. Studies from HIV multidrug patients have associated the use of tenofovir disoproxil fumarate (TDF) with renal dysfunction and phosphate wasting. OBJECTIVE: The aim of this study was to examine the effect of year-long TDF monotherapy on renal function in VHB patients. PATIENTS AND METHODS: We evaluated adult patients diagnosed with VHB before treatment initiation (T0), and after 3 and 12 months (T3 and T12) of TDF initiation. Estimated glomerular filtration rate (eGFR) was estimated by serum cystatin C and creatinine. In addition, urinary electrolytes and tubular biomarkers (cystatin C, ß2-microglobulin and neutrophil gelatinase-associated lipocalin) were analyzed, as well as parathyroid hormone (PTH) and 25(OH)vitamin D levels. RESULTS: After 1 year, 32 patients completed the study, 22 (68.7%) men and 12 (37.5%) Whites, mean age 44.1±12.0 years. We found that serum electrolytes were similar at baseline and 3 or 12 months after initiation of TDF monotherapy. In addition, urinary fractional excretions of electrolytes as well as proteinuria, albuminuria, urinary ß2-microglobulin, and urinary cystatin C showed no significant differences across the treatment timeline. There were also no statistical differences in the eGFR. There was a statistically significant increase in the PTH (Friedman's test, P=0.012), but the 25(OH)vitamin D levels were in the normal range in the beginning and did not change at the follow-up. Moreover, there was no correlation between the initial levels of vitamin D and the corresponding increases in the PTH values. CONCLUSION: If used as monotherapy in hepatitis B patients for a 12-month period, TDF is not associated with changes in either eGFR or a panel of urinary biomarkers. Serum and urinary electrolytes also remained unchanged. Of note, a significant increase in the PTH was found, although not related to the 25(OH)vitamin D initial status.

Quadriceps tendon rupture in maintenance haemodialysis patients: results of surgical treatment and analysis of risk factors.

BACKGROUND: Reports of spontaneous quadriceps ruptures in end-stage renal disease (ESRD) patients are scarce, and the assessment of risk factors for tendon rupture is poorly addressed in the majority of the studies. The purpose of the present study is to report a series of patients on haemodialysis with spontaneous quadriceps tendon ruptures operated at our institution. The results of the surgical treatment are described and the potential risk factors associated with the rupture are analyzed. METHODS: Our study consisted of retrospective analysis of patient's charts. Clinical and laboratory findings of the operated group were compared to the ones of a control group of haemodialysis patients matched by age, gender, and time on haemodialysis, but without tendon rupture. RESULTS: Between 1998 and 2010, six ESRD patients with 11 spontaneous ruptures of the quadriceps tendon were treated at our institution. On postoperative evaluation all patients were able to walk without crutches after six months of follow-up, and there were no new ruptures. Positive serology for Hepatitis C was present in two cases (33%) but in none of the controls (p = 0.034). Mean serum levels of intact parathormone (iPTH) and alkaline phosphatase were both higher in cases (p = 0.013 and p = 0.034, respectively). In contrast, mean serum levels of albumin, ferritin and haemoglobin were all lower in cases (p = 0.008, p = 0.043 and p = 0.016, respectively). CONCLUSION: Reconstructive surgery is a good way to restore knee function in ESRD patients with quadriceps tendon ruptures. Our cases exhibited higher levels of iPTH and alkaline phosphatase than control patients, reinforcing the role of secondary hyperparathyroidism in tendon weakening. They also had a higher frequency of hepatitis C and lower levels of albumin and haemoglobin compared to controls, possibly implicating chronic inflammation as a potential risk factor for tendon rupture.

The chronic kidney disease outcomes and practice patterns study Brazil (CKDopps-Brazil): Design, data and methodology / Estudo dos desfechos de doenca renal cronica e padroes da pratica atual - Brasil (CKDopps-Brazil): Desenho, dados e metodologia

Introduction: The chronic kidney disease outcomes and practice patterns study (CKDopps) is an international observational, prospective, cohort study involving patients with chronic kidney disease (CKD) stages 3-5 [estimated glomerular filtration rate (eGFR) < 60 ml/min/1.73 m2, with a major focus upon care during the advanced CKD period (eGFR < 30 ml/min/1.73 m2)]. During a 1-year enrollment period, each one of the 22 selected clinics will enroll up to 60 advanced CKD patients (eGFR < 30 ml/min/1.73 m2 and not dialysis-dependent) and 20 earlier stage CKD patients (eGFR between 30-59 ml/min/1.73 m2). Exclusion criteria: age < 18 years old, patients on chronic dialysis or prior kidney transplant. The study timeline include up to one year for enrollment of patients at each clinic starting in the end of 2013, followed by up to 2-3 years of patient follow-up with collection of detailed longitudinal patient-level data, annual clinic practice-level surveys, and patient surveys. Analyses will apply regression models to evaluate the contribution of patient-level and clinic practice-level factors to study outcomes, and utilize instrumental variable-type techniques when appropriate. Conclusion: Launching in 2013, CKDopps Brazil will study advanced CKD care in a random selection of nephrology clinics across Brazil to gain understanding of variation in care across the country, and as part of a multinational study to identify optimal treatment practices to slow kidney disease progression and improve outcomes during the transition period to end-stage kidney disease. .

Introdução: O Estudo de padrões da prática e desfechos das doenças renais crônicas (CKDopps) é um estudo internacional observacional, prospectivo, com uma coorte composta de pacientes com doenças renais crônicas (DRC) nos estágios 3-5 [taxa de filtração glomerular estimada (eGFR) < 60 ml/min/1,73 m2, com um grande foco sobre o tratamento durante o período de doença renal crônica avançada (eGFR < 30 ml/min/1,73 m2)]. Durante o período de recrutamento de participantes, de 1 ano, cada uma das 22 clínicas selecionadas inscreverá até 60 pacientes com DRC avançada (eGFR < 30 ml/min/1,73 m2 e não dependente de diálise) e 20 pacientes com DRC em estágios anteriores (eGFR entre 30-59 ml/min/1,73 m2). Os critérios de exclusão são: idade < 18 anos; pacientes em diálise crônica ou transplante de rim prévio. O cronograma de estudo inclui até um ano para a inscrição dos pacientes em cada clínica a partir do final de 2013, sendo então acompanhados por 2-3 anos, com coleta de dados longitudinais detalhados dos pacientes, pesquisas anuais dos níveis da prática na clínica e levantamentos de informação dos pacientes. As análises aplicarão modelos de regressão para avaliar a contribuição de fatores relacionados à clínica e aos próprios pacientes para estudar os desfechos, e utilizar técnicas do tipo: variável instrumental, quando apropriado. Conclusão: Lançado em 2013, o CKDopps-Brasil, avaliará o tratamento de DRC avançada em uma seleção aleatória de clínicas de nefrologia em todo o Brasil para entender como o tratamento varia em nosso país, e como parte de um estudo multinacional para identificar as práticas de tratamento ideal para retardar ...

Associação do índice tornozelo-braço com inflamação e alterações minerais ósseas em pacientes em hemodiálise / Association of ankle-arm index with inflammation and mineral bone disorder in hemodialysis patients / Asociación del índice Tobillo-Brazo con la inflamación y trastornos minerales óseos en pacientes en hemodiálisis

FUNDAMENTO: O índice tornozelo-braço (ITB) reduzido, inflamação e distúrbio mineral ósseo (DMO) estão associados com aumento no risco de morte e complicações cardiovasculares em pacientes em hemodiálise (HD), mas a relação entre esses fatores necessita ser elucidada. OBJETIVO: Avaliar a associação entre ITB anormal e DMO com inflamação em pacientes em HD. MÉTODOS: Esta análise transversal avaliou 478 pacientes em HD por pelo menos 1 ano. O ITB foi avaliado através de um Doppler portátil e manômetro de coluna de mercúrio. Os pacientes foram divididos em três grupos, de acordo com o ITB (baixo: <0,9, normal: 0,9 a 1,3, e alto: >1,3). As medidas de proteína C-reativa foram utilizadas como marcador inflamatório, enquanto a DMO foi avaliada através dos níveis de cálcio, fósforo e hormônio paratireoidiano intacto (iPTH). RESULTADOS: Os participantes tinham 54 (18 a 75) anos, 56 por cento eram do sexo masculino, 17 por cento eram diabéticos e estavam em HM por 5 (1 a 35) anos. A prevalência de ITB baixo, normal e alto AAI foi 26,8 por cento, 64,6 por cento e 8,6 por cento, respectivamente. Usando um modelo de regressão logística condicional com procedimento backward, idade (p<0,001), diabetes (p= 0,001), e níveis de proteína C-reativa >6 mg/L (p= 0,006) estavam associados com a presença de ITB baixo, enquanto o sexo masculino (p<0,001), diabetes (p= 0,001) e produto cálcio x fósforo elevado (p= 0,026) estavam associados com ITB alto. CONCLUSÃO: Em pacientes em HD, a presença de diabetes estava associada com ITB alto e baixo. O risco de ter ITB baixo parece aumentar com a idade e inflamação, enquanto a DMO estava associada com ITB alto.

BACKGROUND: Reduced ankle-arm index (AAI), inflammation and mineral bone disorder (MBD) are all associated with increased risk of death and cardiovascular complications in patients on hemodialysis (HD), but the association between them deserves clarification. OBJECTIVE: To evaluate the association between abnormal AAI with MBD and inflammation in patients on HD. METHODS: This was a cross-sectional analysis of 478 patients on hemodialysis for at least one year. The AAI was evaluated using a portable Doppler and mercury column manometer. Patients were divided into 3 groups, according to AAI (low: <0.9, normal: 0.9 to 1.3, and high: >1.3). C-reactive protein measurement was used as an inflammatory marker, whereas MBD was evaluated by calcium, phosphorus and intact parathyroid hormone levels. RESULTS: Participants were 54 (18 to 75) years old, 56 percent males, 17 percent diabetics, and had been on hemodialysis for a mean of 5 (1 to 35) years. The prevalence of low, normal and high AAI was 26.8 percent, 64.6 percent and 8.6 percent, respectively. Using a backward conditional logistic regression model, age (p<0.001), diabetes (p= 0.001), and C-reactive protein levels >6 mg/L (p= 0.006) were associated with the presence of low AAI, whereas male gender (p<0.001), diabetes (p= 0.001) and elevated calcium x phosphorus product (p= 0.026) were associated with high AAI. CONCLUSION: In patients on hemodialysis, the presence of diabetes was associated with both low and high AAI. The risk of having low AAI seems to be increased by aging and inflammation, whereas BMD was associated with high AAI.

FUNDAMENTO: El índice tobillo-brazo (ITB) reducido, la inflamación y el trastorno mineral óseo (TMO) se asocian con mayor riesgo de muerte y complicaciones cardiovasculares en pacientes sometidos a hemodiálisis (HD), pero la relación entre estos factores debe ser aclarada. Objetivos: Evaluar la asociación entre el ITB anormal la TMO con inflamación en paciente en HD. MÉTODOS: Este análisis transversal evaluó a 478 pacientes en HD durante al menos 1 año. El ITB se midió con un Doppler portátil y manómetro de columna de mercurio. Los pacientes fueron divididos en tres grupos, de acuerdo al ITB (bajo: < 0,9, normal: 0,9 a 1,3, y alto: > 1,3). Las mediciones de proteína C-reactiva se utilizaron como marcador inflamatorio, mientras que la TMO se evaluó a través de los niveles de calcio, fósforo y hormona paratiroidea intacta (iPTH). RESULTADOS: Los participantes tenían 54 (18-75) años, el 56 por ciento eran del sexo masculino, el 17 por ciento eran diabéticos y estaban se encontraban en HD por 5 (1 a 35) años. La prevalencia de ITB bajo, normal y alto ITB fue de un 26,8 por ciento, un 64,6 por ciento y un 8,6 por ciento respectivamente. Al utilizar un modelo de regresión logística condicional con el procedimiento backward (hacia atrás), diabetes (p < 0,001), y niveles de proteína C-reactiva > 6 mg/l (p = 0,006) estaban asociados con la presencia de ITB bajo, mientras que el sexo masculino (p < 0,001), diabetes (p = 0,001) y producto calcio x fósforo elevado (p = 0,026) estaban asociados con ITB alto. CONCLUSIÓN: En los pacientes en HD, la presencia de la diabetes estaba asociada con ITB alto y bajo. El riesgo de tener ITB bajo parece aumentar con la edad y la inflamación, mientras que la TMO estaba asociada con ITB alta. (Arq Bras Cardiol 2011;96(5):405-410).

Prehypertension and cardiovascular risk factors in adults enrolled in a primary care programme.

BACKGROUND: An increase in cardiovascular (CV) disease has been observed in prehypertensive subjects who frequently carry other cardiovascular risk factors. In Brazil, little is known about prehypertension and its association with cardiovascular risk factors. OBJECTIVE: To estimate the association between prehypertension and cardiovascular risk factors in a public primary healthcare programme. METHODS: Associations in this cross-sectional study were estimated on the basis of generalized estimating equations. Results are expressed as odds ratio (OR) or adjusted odds ratio (OR(a)) with 95% confidence interval (CI). RESULTS: The 357 participants were classified as normotensive (64.4%) or prehypertensive (35.6%). In a univariate analysis, prehypertension was statistically associated with male gender, age, table salt use, diabetes, body mass index (BMI), uric acid, and all lipids except high-density lipoprotein cholesterol. When analysis was performed adjusting for gender, age, and table salt use, the association of each metabolic parameter with prehypertension, remained significant for BMI (OR(a) = 1.097; 95% CI 1.035-1.162), triglycerides (OR(a) = 1.008; 95% CI 1.003-1.013), and uric acid (OR(a) = 1.269; 95% CI 1.023- .576). To check for their independence of obesity, associations of triglycerides and uric acid with prehypertension were reanalysed after adjustment for BMI. The association of triglycerides remained statistically significant. A trend of association was present for uric acid. The prevalence of prehypertension paralleled the increase of the number of risk factors. CONCLUSION: Prehypertension in Brazil is associated with well-recognized cardiovascular risk factors even in a continuously monitored population such the one under study. Prehypertension can be a valuable clue to alert health professionals to treat underlying perturbations to prevent overt cardiovascular disease.

Increased nitric oxide production in platelets from severe chronic renal failure patients.

Nitric oxide (NO) production occurs through oxidation of the amino acid L-arginine by NO synthase (NOS). NO inhibits platelet activation by increasing the levels of cyclic guanosine monophosphate (cGMP), thus maintaining vascular homeostasis. Our group previously demonstrated (da Silva et al. 2005) an enhancement of the L-arginine-NO-cGMP pathway in platelets taken from chronic renal failure (CRF) patients on haemodialysis associated with reduced platelet aggregation. We investigate the platelet L-arginine-NO-cGMP pathway, platelet function, and inflammation from patients in CRF on conservative treatment. A total of 42 CRF patients and 42 controls (creatinine clearance = 27 ± 3 vs. 93 ± 1 mL per min per 1.73 m2, respectively) participated in this study. NOS activity and expression and cGMP concentration were measured in platelets. Platelet aggregation induced by collagen or ADP was evaluated and plasma levels of fibrinogen were determined by the Clauss method. A marked increase in basal NOS activity was seen in undialysed CRF patients compared with controls, accompanied by an elevation of fibrinogen plasma levels. There were no differences in expression of NOS and in cGMP levels. In this context, platelet aggregation was not affected. We provide the first evidence of increased intraplatelet NO biosynthesis in undialysed CRF patients, which can be an early marker of future haemostatic abnormalities during dialysis treatment.

Histologic evolution of bone disease 6 months after successful kidney transplantation.

BACKGROUND: The histologic patterns of bone disease, as well as the evolution of renal osteodystrophy after kidney transplantation (Tx), are not well defined. Information in this regard is scarce and contradictory. METHODS: Before and 6 months after Tx, analysis of biochemical, hormonal, and bone histomorphometric parameters were performed. Twenty patients (14 men and 6 women) entered the study. Median age was 36.5 (range, 20 to 55) years, and median time on dialysis was 22 (9 to 88) months. RESULTS: Bone histomorphometric diagnoses at pre-Tx were adynamic bone disease, 12; mixed bone disease, 3; mild disease, 3; and osteitis fibrosa, 2. After Tx, 11 had adynamic bone disease; 8, mild disease; and 1, osteomalacia. As a whole, dynamic parameters improved significantly in patients who had adynamic bone. Five of the 12 with this diagnosis completely recovered their bone turnover. Pre-Tx hyperparathyroidism bone features improved or resolved, but 5 of the 8 patients had low-turnover bone disease (adynamic disease, 4; osteomalacia, 1). Three of them had persistence of aluminum and/or iron deposits on bone surface, and the other 2 had hypophosphatemia and high intact parathyroid hormone levels. Overall, biochemical parameters tended toward normalization. Serum intact parathyroid hormone before Tx was correlated negatively with post-Tx trabecular thickness. CONCLUSION: Six months after Tx, bone histology remained abnormal. The high turnover bone disease improved in all cases, but in most of them low turnover bone disease emerged. Nearly half of the cases with pre-Tx adynamic bone disease recovered their bone turnover completely with some improvement observed in the majority of the remaining cases.

Prospective evaluation of an in-center daily hemodialysis program: results of two years of treatment.

Short duration daily hemodialysis (DHD) emerges as a well-tolerated alternative to standard hemodialysis (SHD). In this prospective study 5 patients in SHD were recruited to participate in an in-center DHD program. The SHD consisted of 3 sessions of 4 h each per week. Nonproportional mixture machines without an ultrafiltration control device and low flow dialyzers were used. For DHD, dialysis equipment and procedures were kept the same. Dialysis sessions, however, began at 6 p.m. (from Monday to Saturday) and lasted 2 h. Data from the last 6 months on SHD of the same patients were compared with the ones from each semester on DHD. Bone biopsy was performed at start and at the end of the 2-year study period. Hypotensive episodes, hypertensive crisis, cramps and headaches became 7-10 times less frequent in daily dialysis. A significant fractional increase ( approximately 12%) was seen in mean values for hematocrit. Predialysis urea levels as well as predialysis creatinine levels declined significantly. Also lower during the daily dialysis period were the mean values for both phosphorus and CaxP product. Significant increases were found in serum bicarbonate, albumin and in dry weight. The frequency of mean blood pressure >/=110 mm Hg on arrival for dialysis was significantly lower in every semester on daily hemodialysis. A significant twofold improvement in quality of life scoring was observed. Finally, daily hemodialysis also seemed to be beneficial to low turnover bone disease and bone aluminum deposition. These beneficial effects occurred despite of an increase in the frequency of missing days. Results from the present study which prospectively addressed the role of in-center short daily hemodialysis in the management of ESRD are encouraging.

Atividade imunossupressora de preparaçöes de cicliosporina A em células mononucleares / Immunossupressive activity of cyclosporine A formulations in mononuclear cells

Compara a atividade imunossupressora in vitro de duas preparaçöes comerciais de ciclosporina A (Sigmasporin Microoral, da Sigmapharma, e Sandimmun Neoral, da Novartis) em células mononucleares de voluntários sadios e pacientes renais crônicos. Os dois medicamentos, em suas embalagens comerciais, foram solicitados a uma farmácia hospitalar, tranferidos para frascos indênticos e rotulados como ciclosporina 1 (CsA1) e 2 (CsA2) por pesquisador independente. Foi estabelecida uma curva de concentraçäo das duas preparaçöes, e avaliada sua capacidade de inibiçäo da proliferaçäo de células mononucleares induzida por fito-hemaglutina (PHA) em culturas de células mononucleres do sangue periférico e em sangue total obtidas a partir de voluntários sadios e, também, em sangue total de pacientes hemodialisados. O estudo demonstrou que as duas preparaçöes comerciais säo imunossupressoras com curvas semelhantes, embora estatísticamente diferentes no que se refere à inibiçäo da proliferaçäo de células mononucleares induzida por PHA em linfócitos do sangue periférico e em sangue total de pacientes hemodialisados nas concentraçöes testadas. As duas preparaçöes comerciais de ciclosporina apresentam atividade imunossupressora equivalente in vitro.(au)