João Egidio Romão

Obstetric Outcome in Pregnant Women on Long-term Dialysis: A Case Series

BACKGROUND Although still uncommon, pregnancy frequency in women on maintenance hemodialysis therapy has increased in the past 20 years. Most published reports suggest that intensified hemodialysis regimens result in better pregnancy outcomes. The small number of patients investigated in all reported series is the main limitation of the available studies. STUDY DESIGN Retrospective case series. SETTING & PARTICIPANTS Data for all pregnancies that occurred in 1988-2008 in women undergoing maintenance hemodialysis (52 pregnancies) at the São Paulo University Medical School (São Paulo, Brazil). OUTCOMES & MEASUREMENTS We analyzed maternal and fetal outcomes of 52 pregnancies, as well as their relationship with various clinical, laboratory, and hemodialysis parameters, such as pre-eclampsia, pregnancy before or after dialysis therapy, hemodialysis dose, polyhydramnios, anemia, and predialysis serum urea level. In addition, logistic regression models for a composite adverse fetal outcome (perinatal death or extremely premature delivery) and linear regression models for birth weight were built. RESULTS 87% overall rate of successful delivery, with a mean gestational age of 32.7 +/- 3.1 weeks. Pre-eclampsia was associated with a poor prognosis compared with pregnancies without pre-eclampsia: a successful delivery rate of 60% versus 92.9% (P = 0.02), extremely premature delivery rate of 77.8% versus 3.3% (P < 0.001), lower gestational age (P < 0.001), and birth weight (P < 0.001). Patients with an adverse composite fetal outcome had a higher frequency of pre-eclampsia (P < 0.001), lower frequency of polyhydramnios (P = 0.03), lower third-trimester hematocrit (P = 0.03), and higher predialysis serum urea level (P = 0.03). The same results were seen for birth weight. LIMITATIONS Retrospective data analysis. The absence of creatinine clearance measurements did not allow evaluation of the impact of residual renal function on fetal outcome. CONCLUSIONS Outcomes of pregnancy in women undergoing hemodialysis often are good. Pre-eclampsia, third-trimester hematocrit, polyhydramnios, and predialysis serum urea level are important variables associated with fetal outcome and birth weight.

Effects of bone remodelling on calcium mass transfer during haemodialysis

BACKGROUND During haemodialysis, calcium balance can affect, or be affected by, mineral metabolism. However, when dialysate calcium concentration (d[Ca]) is chosen or kinetic models are employed to calculate calcium balance, bone remodelling is rarely considered. In this study, we examined whether bone remodelling affects calcium mass transfer during haemodialysis. METHODS We dialysed 23 patients using a d[Ca] of 1.0, 1.25, 1.5 or 1.75 mmol/L. Calcium mass transfer was measured and associated with remodelling bone factors. RESULTS Calcium balance varied widely depending on the d[Ca]. Calcium removal was -578 +/- 389, -468 +/- 563, +46 +/- 400 and +405 +/- 413 mg when a d[Ca] of 1.0, 1.25, 1.5 or 1.75 mmol/L was used, respectively (1.0 and 1.25 vs 1.5 and 1.75 mmol/L, P < 0.001; 1.5 vs 1.75 mmol/L, P < 0.05). Univariate analysis showed that calcium balance correlated with calcium gradient, parathyroid hormone (PTH), osteocalcin and dialysis vintage. Multivariate analysis revealed that calcium balance was dependent on calcium gradient, PTH and osteocalcin. CONCLUSIONS These results suggest that bone remodelling could affect calcium mass transfer during haemodialysis.

Pruritus in hemodialysis patients: The problem remains

Pruritus is still one of the most common and disturbing symptoms of end‐stage renal disease. The objective of this study is to analyze the prevalence of pruritus in hemodialysis patients and the possible factors implicated in its genesis. In a cross‐sectional study, 101 patients on hemodialysis at our center were screened for pruritus. The relationship of various factors with pruritus was evaluated. Of the 101 patients included, 31(30.7%) had pruritus at the time of examination. Patients with pruritus were significantly older than those without pruritus (P=0.0027). Pruritus tended to be more prevalent in patients undergoing dialysis 3 times a week than in those undergoing daily dialysis, but the difference did not reach statistical significance (P=0.0854). Lower transferrin saturation levels were found in patients with pruritus than in those without pruritus (P=0.0144). C‐reactive protein levels were significantly higher in patients with pruritus than in those without pruritus (P=0.0013). There was no significant difference between the groups in the levels of the other inflammatory biomarkers measured. However, there was a tendency toward a correlation between the levels of α‐1‐glycoprotein and the intensity of pruritus (P=0.0834). Our results suggest a possible relationship of the inflammatory response upregulation to pruritus. Additionally, there was a positive relationship between pruritus and iron deficiency, possibly associated with inflammatory elevation of hepcidin. A better understanding of the factors implicated in the genesis of pruritus related to end‐stage renal disease is crucial in the development of more effective treatments for this symptom.

Positive Acute-Phase Inflammatory Markers in Different Stages of Chronic Kidney Disease

Background: An elevated serum level of acute-phase inflammatory markers is associated with an increased risk of cardiovascular disease. We hypothesized that elevated acute-phase inflammatory markers are directly associated with the different stages of chronic kidney disease (CKD). Methods: We evaluated the relationship between serum levels of high-sensitivity C-reactive protein (hsCRP) and α1-acid glycoprotein (α1-AGP), as well as the renal function in 224 adult patients with CKD (mean age 56.6 years, 46% male, and 40% diabetics), stratified according to the glomerular filtration rate (GFR) (based on the National Kidney Foundation/Kidney Dialysis Outcomes Quality Initiatives), and in 94 hemodialysis patients. Results: The mean hsCRP was 8.2 ± 12.1 mg/l, and hsCRP levels were >5 mg/l in 44.4% of the patients; α1-AGP levels were >125 mg/dl in 33.3% of the patients. Mean hsCRP and α1-AGP were significantly higher in more severe stages of CKD. A weak inverse relationship was found between GFR and serum hsCRP (r = –0.2205; p = 0.0006) and between GFR and serum α1-AGP (r = –0.3266; p < 0.0001). There was a correlation between hsCRP and α1-AGP (r = 0.3417; p < 0.0001). No significant differences were detected between patients with CKD and those undergoing hemodialysis concerning hsCRP (8.2 ± 12.1 vs. 6.8 ± 7.4 mg/l; p = 0.2980) and α1-AGP (116.3 ± 42.5 vs. 117.2 ± 37.9 mg/dl; p = 0.8590). However, the level of hsCRP was significantly reduced in hemodialysis patients compared with patients with stage 5 predialytic disease (12.1 ± 13.9 to 6.8 ± 7.4 mg/l; p = 0.005). More patients with stage 5 predialytic CKD had an elevated hsCRP serum level compared with patients on hemodialysis (64.7 vs. 37.9%; χ2 = 6.230, p < 0.01). Conclusions: Approximately 50% of patients with CKD – even in the early phase of renal failure – exhibit an activated acute-phase response, which is closely related to the stages of CKD. Hemodialysis may partially correct the inflammatory process present in the immediate predialysis phase of CKD.

Early Elevation of Lipoprotein(a) Levels in Chronic Renal Insufficiency

Serum lipoprotein(a) [Lp(a)] concentrations in chronic renal failure patients were investigated in relation to the degree of renal insufficiency, treatment by maintenance hemodialysis, and correction of uremia by renal transplantation with or without cyclosporin immunosuppression. Fast serum levels of Lp(a) (mg/100 mL) were determined in 34 chronic renal failure patients not in need of maintenance dialysis (16 with serum creatinine 2.0-4.0 mg/100 mL; 18 with serum creatinine higher than 4.0 mg/100 mL), 40 patients treated by hemodialysis, 55 successful renal transplant recipients (28 under cyclosporin treatment and 27 receiving no cyclosporin), and 34 healthy controls. Age and sex distributions were similar among groups. Pregnant women; non-White individuals; subjects with obesity, diabetes, nephrotic syndrome, and hepatic and thyroid diseases; and those treated with oral contraceptives or lipid-lowering drugs were excluded from the study. Compared to controls, median Lp(a) was increased in nondialyzed renal failure patients (11 vs. 47.5 p < 0.001) and this was the only lipid abnormally observed in the group. There was no significant difference in Lp(a) levels between nondialized renal failure patients with serum creatinine 2.0-4.0 and > 4.0 mg/100 mL (47 vs. 49, NS). Moreover, Pearson correlation coefficient (r = 0.01, NS) showed that Lp(a) values were not related to serum creatinine in nondialyzed patients, In hemodialysis subjects Lp(a) concentrations (median = 29) were intermediate between those observed in nondialyzed patients and controls but the differences were not significant. Lp(a) levels in renal transplant patients treated with cyclosporin (median = 6) and not receiving cyclosporin (median = 13) were similar and did not differ from controls. Serum Lp(a) increases and attains maximum levels with mild/moderate reduction in renal function, and does not seem to change through late renal failure stages or in relation to the introduction of maintenance hemodialysis treatment. Correction of uremia by successful renal transplant caused normalization of Lp(a) levels regardless of the use of cyclosporin. Increased Lp(a) levels may be the earliest and more consistent lipid alteration seen in predialysis renal failure.

Conversion to sirolimus in kidney-pancreas and pancreas transplantation.

Reports on the use of sirolimus (SRL) in pancreas transplantation are still limited. The aim of this study was to evaluate the outcome of SRL conversion in pancreas transplant patients. Among 247 patients undergoing simultaneous kidney-pancreas or solitary pancreas transplantation, 33 (13%) were converted to SRL. The reasons for conversion were calcineurin inhibitors (CNI) nephrotoxicity (n = 24; 73%), severe neurotoxicity owing to CNI (n = 1; 3%), severe and/or recurrent acute rejection episodes (n = 7; 21%), gastrointestinal (GI) side effects of mycophenolate mofetil (MMF; n = 5; 15%), and hyperglycemia (n = 4; 12%). Before conversion, all patients were maintained on a CNI, MMF, and low-dose steroids. They were gradually converted to SRL associated with either CNI or MMF withdrawal. Sixty-three percent (n = 15) of patients who were converted owing to CNI nephrotoxicity, showed stable or improved renal function. At 12 months after conversion, serum creatinine levels were significantly decreased in this group (2.2 +/- 0.5 vs 1.6 +/- 0.3 mg/dL; P = .001) and C-peptide values increased (2.9 +/- 1.1.1 vs 3.1 +/- 1.3 nmol/L; P = .018). The only patient with leucoencephalopathy showed improved neurologic status after SRL conversion. All patients converted to SRL because of GI side effects of MMF showed improvements, and none of those converted because of hyperglycemia experienced improvement. There were no episodes of acute rejection after conversion. We concluded that conversion to SRL in pancreas transplantation should be considered an important alternative strategy, particularly for CNI nephrotoxicity and neurotoxicity, and in cases of severe diarrhea due to MMF.

End-stage renal failure and national resources : The Brazilian experience

Brazil is the fifth largest and the fifth most populous nation in the world. Its economy rivals Mexico as the strongest in Latin America and ranks among the 15 largest economies in the world. Despite these achievements, a substantial fraction of the Brazilian population still lives in poverty, and many still have limited access to medical assistance. There are currently about 380 patients on hemodialysis per million populations (pmp), approximately one third of the U.S. prevalence, suggesting that a large fraction of end-stage renal disease (ESRD) patients are not diagnosed and treated properly. In Brazil, access to renal replacement therapy (RRT), including renal transplantation, is universal, and the corresponding costs, including those of medications (immunosuppressors and treatment of ESRD complications), are covered by the Brazilian government. However, given the continuous growth of the ESRD population and of the costs incurred by RRT, the efficacy and reach of this system may be severely limited in years to come. In the current struggle against the ESRD epidemics, the Brazilian medical community and health authorities face a triple challenge: to limit the incidence of renal disease, slow or detain the progression of established chronic nephropathies, and ensure that access to quality RRT remains granted to all those who, despite all efforts, reach ESRD.

Outcome of acute renal failure associated with cardiac surgery in infants

OBJECTIVE To analyze the impact of acute renal failure (ARF) on the evolution of infants undergoing cardiac surgery. METHODS We assessed 15 infants undergoing cardiac surgery who developed (ARF). Their demographic, clinical and surgical data, and evolution were analyzed. RESULTS Their mean age was 4.4+/-4.0 months (8 days to 24 months). Twelve infants were males, and 4 patients already had ARF at surgery. The primary cause of ARF was immediate acute cardiac dysfunction in 10 infants, cardiac dysfunction associated with sepsis in 2 infants, and isolated sepsis in 3 infants. All children depended on mechanical ventilation during their postoperative period, 14 infants used vasoactive drugs, and 11 had an infectious process associated with ARF. Thirteen infants required dialytic treatment. Eleven infants developed oluguric ARF, and all had to undergo peritoneal dialysis; of the 4 patients with non-oliguric, 2 required dialysis, the main indication being hypervolemia. Of these 13 dialyzed infants, 4 died in the first 24 hours because of the severity of the underlying cardiac disease (mean urea level of 49+/-20 mg/dl). The mortality rate for the entire group was 60%, and it was higher among the patients with oliguria ARF (73% vs 25%, p<0. 001). The cause of death was acute cardiac dysfunction in 6 infants (early type-1 ARF) and sepsis in the 3 remaining infants (late type-2 ARF). CONCLUSION The mortality rate of ARF associated with cardiac surgery in infants was hight, being higher among children with oliguria; peritoneal dialysis was indicated due to clinically uncontrolled hypervolemia and not to the uremic hypercatabolic state.

Ankle-Brachial Index: A Simple Way to Predict Mortality among Patients on Hemodialysis - A Prospective Study

Background Ankle-brachial index (ABI) can access peripheral artery disease and predict mortality in prevalent patients on hemodialysis. However, ABI has not yet been tested in incident patients, who present significant mortality. Typically, ABI is measured by Doppler, which is not always available, limiting its use in most patients. We therefore hypothesized that ABI, evaluated by a simplified method, can predict mortality in an incident hemodialysis population. Methodology/Principal Findings We studied 119 patients with ESRD who had started hemodialysis three times weekly. ABI was calculated by using two oscillometric blood pressure devices simultaneously. Patients were followed until death or the end of the study. ABI was categorized in two groups normal (0.9–1.3) or abnormal (<0.9 and >1.3). There were 33 deaths during a median follow-up of 12 months (from 3 to 24 months). Age (1 year) (hazard of ratio, 1.026; p = 0.014) and ABI abnormal (hazard ratio, 3.664; p = 0.001) were independently related to mortality in a multiple regression analysis. Conclusions An easy and inexpensive technique to measure ABI was tested and showed to be significant in predicting mortality. Both low and high ABI were associated to mortality in incident patients on hemodialysis. This technique allows nephrologists to identify high-risk patients and gives the opportunity of early intervention that could alter the natural progression of this population.

Bioelectrical Impedance Analysis and Skinfold Thickness Sum in Assessing Body Fat Mass of Renal Dialysis Patients

OBJECTIVE In chronic renal failure patients under hemodialysis (HD) treatment, the availability of simple, safe, and effective tools to assess body composition enables evaluation of body composition accurately, in spite of changes in body fluids that occur in dialysis therapy, thus contributing to planning and monitoring of nutritional treatment. We evaluated the performance of bioelectrical impedance analysis (BIA) and the skinfold thickness sum (SKF) to assess fat mass (FM) in chronic renal failure patients before (BHD) and after (AHD) HD, using air displacement plethysmography (ADP) as the standard method. DESIGN This single-center cross-sectional trial involved comparing the FM of 60 HD patients estimated BHD and AHD by BIA (multifrequential; 29 women, 31 men) and by SKF with those estimated by the reference method, ADP. Body fat-free mass (FFM) was also obtained by subtracting the total body fat from the individual total weight. RESULTS Mean estimated FM (kg [%]) observed by ADP BHD was 17.95 ± 0.99 kg (30.11% ± 1.30%), with a 95% confidence interval (CI) of 16.00 to 19.90 (27.56 to 32.66); mean estimated FM observed AHD was 17.92 ± 1.11 kg (30.04% ± 1.40%), with a 95% CI of 15.74 to 20.10 (27.28 to 32.79). Neither study period showed a difference in FM and FFM (for both kg and %) estimates by the SKF method when compared with ADP; however, the BIA underestimated the FM and overestimated the FFM (for both kg and %) when compared with ADP. CONCLUSION The SKF, but not the BIA, method showed results similar to ADP and can be considered adequate for FM evaluation in HD patients.