Roberto Marcén

Prognosis of Acute Tubular Necrosis: An Extended Prospectively Contrasted Study

The ability to predict the outcome in acute tubular necrosis (ATN) remains elusive despite considerable efforts. Accurate prediction is a crucial priority and has large economical and ethical implications, mainly to judge when treatment is futile and further efforts only prolong miserable agony. To analyze the influence of risk factors in the prognosis of ATN, we applied, in an initial phase, a prospective protocol of demographic data, cause of renal failure, diuresis, need of dialysis and clinical conditions in 228 patients using multiple linear and logistic regression models. In a control phase with 100 consecutive patients, we checked the accuracy of the results previously obtained, evaluating further the overall population of 328 patients in a synthetic phase. Finally, the validation of the equations obtained was verified in 25 patients from another hospital. As a complement of this 4-phase study, detailed statistical comparisons between both linear and logistic multiple regression models were undertaken. Correlation between probability of death obtained with equations from the initial phase applied to control patients and real evolution of these patients, survival or death, was excellent. The study of the synthetic phase revealed coma, assisted respiration, hypotension, oliguria and jaundice as having an independent positive influence on mortality and nephrotoxic etiology and normal consciousness on good prognosis. For the linear model, the same cut-off point of discriminant score (0.9) above which there were no chances for survival could be established in the 4 phases. With the logistic model, it only was found at later phases. The multiple linear was better than the logistic regression model in terms of better correlation with real mortality, better sensitivity and specificity intervals, easier use of discriminant cut-off point and better adjustment of distribution of standardized residuals to expected normal function. Early prognosis of ATN is possible and can be given using simple clinical features. A discriminant score allows to distinguish patients without chances for survival. The multiple linear is better than the logistic regression model in the prediction of the outcome in ATN.

Easy and Early Prognosis in Acute Tubular Necrosis: A Forward Analysis of 228 Cases

Multiple factors still influence the high rate of mortality in acute tubular necrosis. Trying to analyze the influence of each risk factor present in an individual patient and the possible interdependence between these factors, as well as to obtain an early prognosis, we have applied a forward analysis to demographic data, acute renal failure origin, need of dialysis, diuresis and clinical conditions in 228 patients, using a multiple linear regression model contained in a computer package. Based on this approach we have found that three variables: deep neurological coma, persistent blood hypotension and assisted respiration have significant influence on mortality. Also, a regression equation was obtained which could be applied as a discriminant score to patient prognosis. This score, calculated with the three aforementioned variables and oliguria when the nephrologist sees the patient for the first time, allows an easy and early prognosis in each patient with acute tubular necrosis.

Antibody Level after Hepatitis B Vaccination in Hemodialysis Patients: Influence of Hepatitis C Virus Infection

Seroconversion after hepatitis B vaccine has been estimated to occur when the level of anti-HBs is higher than 10 IU/1, but recently is has been considered that an antibody titer above 100 IU/1 is necessary to guarantee an efficacious protection. We prospectively studied the evolution of anti-HBs after primary vaccination (3 doses; Engerix B, 40 mu g each) in 56 seronegative and not previously vaccinated hemodialysis patients. Three months after vaccine administration, seroconversion (anti-HBs > 10 IU/1) was found in 43 patients (76.7%), but an adequate response (titer > 100 IU/1) was observed only in 30 (53.5%). At 1 year after vaccination only 1 (3.3%) of the 30 cases with an effective response had lost his anti-HBs, while 12 of the 13 patients (92.3%) with an inadequate response (anti-HBs between 10 and 100 IU/1) had no detectable antibodies (p < 0.01, chi2). Considering that an antibody titer above 100 IU/1 following vaccination is necessary in order to maintain that level of antibody 1 year later, we analyzed the factors which influenced obtaining this level of antibody. Age, time on hemodialysis, serum albumin, Kt/V and protein catabolic rate did not affect the response to the vaccine. Females had a better response than males, and interestingly we found that hepatitis C virus (HCV) infection influenced the level of immunity. 27 out of the 43 HCV-negative cases (62.7%) obtained anti-HBs levels greater than 100 IU/1, but only 3 out of the 13 HCV-infected patients (23%) had an anti-HBs above 100 IU/1 (p < 0.01, chi2). Our results suggest that after hepatitis B vaccine, an antibody titer higher than 100 IU/1 is necessary to maintain the antibody level 1 year later, and that HCV infection may reduce the effectiveness of hepatitis B vaccine in hemodialysis patients.

Epidemiology of Symptomatic Hypotension in Hemodialysis: Is Cool Dialysate Beneficial for All Patients?

A prospective study on hypotension in hemodialysis was performed in 60 nondiabetic patients at two different dialysate temperatures during 12 months. A 37 degrees C bath (3,723 sessions) was used and after the first 6 months the temperature was changed to 35 degrees C (4,019 sessions). The prevalence of symptomatic hypotension was 15.3% and it was closely correlated with the presence of other symptoms. The most affected populations were women, patients over 55 years of age, patients with low body surface area and patients with a cardiovascular disease. A slight but significant decrease of symptomatic hypotension was seen by using a 35 degrees C dialysate (16.4 vs. 14.3%, p less than 0.01). In patients with frequent hypotension (in up to 30% of sessions), cool dialysate significantly reduced the incidence of the symptom (44.2 vs. 34.1%, p less than 0.001). These results were obtained in spite of a greater interdialysis weight gain at low temperature (2 +/- 0.6 vs. 1.9 +/- 0.7 kg, p less than 0.001). We consider that low-temperature dialysis is a simple, useful and economic procedure, especially for highly symptomatic patients. The association of cooling dialysate with higher sodium concentration, bicarbonate and special membranes could reduce dialysis symptoms dramatically.

Outcome of cadaveric renal transplant patients treated for 10 years with cyclosporine : Is chronic allograft nephropathy the major cause of late graft loss?

Background. The introduction of cyclosporine (CsA) has improved the short-term outcome of renal transplantation, but its effect on the long-term survival is not well known. Methods. We analyzed 128 cadaveric first renal transplant recipients with CsA and prednisone as basal immunosuppression followed for at least 10 years, and we have compared them with a group of 185 historical patients treated with azathioprine (Aza) and prednisone. Results. The 1-year graft survival was 83% in the CsA-treated patients and 68% in the Aza-treated patients (P <0.025), and the differences were significant for 3 years. Acute rejection accounted for the 10.9% of losses in CsA-treated patients and for 23.8% of losses in Aza-treated patients (P =0.046). Chronic allograft nephropathy was the cause of graft losses in 40.6% and 16.8% of cases (P =0.008). Patient survival at 5 years was 88% in CsA-treated patients and 79% in the Aza-treated patients (P <0.025). When analyzing the data of the 64 CsA-treated patients and the 84 Aza-treated patients with one functioning graft at 10 years, mean serum creatinine values were significantly higher in the CsA-treated patients at all time points but the increases were not significantly different. At 10 years, mean blood pressure was higher (P =0.002), and hypercholesterolemia (P =0.011) and hyperuricemia (P =0.000) were more prevalent in the CsA-treated patients. Conclusions. CsA resulted in a better short-time patient and graft survival that was not maintained in the long-term outcome. Chronic allograft nephropathy was the leading cause of graft loss in CsA-treated patients. Graft function was poorer in the CsA-treated patients, but its decline was similar in the two groups.

Impairment of Tubular Secretion of Urate in Renal Transplant Patients on Cyclosporine

The prevalence of hyperuricemia was investigated in 214 kidney allograft recipients, 81 were on azathioprine and steroids and 133 on cyclosprine (CyA) and low-dose steroids or on triple therapy. All had stable renal function, serum creatinine < 2.5 mg/dl, and a follow-up between 12 and 120 months. At the time of the study, blood and urine samples were obtained to perform tests of renal function. The renal handling of urate was evaluated by a combined pyrazinamide and probenecid test in 35 selected patients (12 normouricemic on azathioprine, 9 normouricemic on CyA and 14 hyperuricemic on CyA). The prevalence of hyperuricemia was higher in the group of patients on CyA (19.7 vs. 66.9%, p < 0.001), as well as the concentration of serum urate (6.1 +/- 1.9 vs. 7.6 +/- 1.7, p < 0.001), and serum creatinine (1.2 +/- 0.3 vs. 1.4 +/- 0.4, p < 0.001). In patients on CyA, multivariate analysis showed that the most important predictive variables of hyperuricemia were: serum creatinine, FEurate, diuretic use and CyA blood levels (r = 0.73, p < 0.0001). Thirteen patients on CyA (9.9%) had at least one episode of gouty arthritis. Those patients were older than the hyperuricemic patients without gout (45.7 +/- 6.7 vs. 37.1 +/- 13.5 years, p < 0.01), had worse renal function (serum creatinine 1.9 +/- 0.4 vs. 1.5 +/- 0.4 mg/dl, p < 0.01), and higher prevalence of hypertension (100 vs. 63.1%, p < 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Patient outcomes after kidney allograft loss

Despite considerable advances in immunosuppression and in short-term graft survival, little improvement has been observed in long-term survival rates. About 30% of patients lose their graft in the first 5 years, and this percentage increases up to 50% at 10 years. Graft losses, due to causes other than death with functioning graft, are an important cause of end-stage renal disease. Patients with failed graft account for 4% to 10% of those admitted yearly for dialysis therapy. There is no evidence about the superiority of hemodialysis or peritoneal dialysis in the treatment of these patients. Graft failure seems to be an important risk factor associated with morbidity and mortality, mostly in the first months after restarting dialysis. The causes of these high morbidity and mortality rates are not very well known. However, a poor control of the chronic kidney disease complications, the persistence of a chronic inflammatory state due to the failed graft, and the lack of a protective effect of the functioning graft could play an important role. This inflammatory state could be mediated by the presence of the rejected graft, and nephrectomy has been recommended. A variable number of patients with failed graft are relisted for a new transplant, thus increasing the shortage of organs. Graft survival of repeat transplantation with the new immunosuppressive regimens is very close to that of first-graft survival. Moreover, retransplantation increases patient survival rates in some series when compared with patients on dialysis. Complications during the first transplant such as BK virus nephropathy or lymphoproliferative diseases do not necessarily recur after the repeat transplant.

Risk factors for graft loss and mortality after renal transplantation according to recipient age: a prospective multicentre study

Background To describe the causes of graft loss, patient death and survival figures in kidney transplant patients in Spain based on the recipients age. Methods The results at 5 years of post-transplant cardiovascular disease (CVD) patients, taken from a database on CVD, were prospectively analysed, i.e. a total of 2600 transplanted patients during 2000–2002 in 14 Spanish renal transplant units, most of them receiving their organ from cadaver donors. Patients were grouped according to the recipients age: Group A: <40 years, Group B: 40–60 years and Group C: >60 years. The most frequent immunosuppressive regimen included tacrolimus, mycophenolate mofetil and steroids. Results Patients were distributed as follows: 25.85% in Group A (>40 years), 50.9% in Group B (40–60 years) and 23.19% in Group C (>60). The 5-year survival for the different age groups was 97.4, 90.8 and 77.7%, respectively. Death-censored graft survival was 88, 84.2 and 79.1%, respectively, and non death-censored graft survival was 82.1, 80.3 and 64.7%, respectively. Across all age groups, CVD and infections were the most frequent cause of death. The main causes of graft loss were chronic allograft dysfunction in patients <40 years old and death with functioning graft in the two remaining groups. In the multivariate analysis for graft survival, only elevated creatinine levels and proteinuria >1 g at 6 months post-transplantation were statistically significant in the three age groups. The patient survival multivariate analysis did not achieve a statistically significant common factor in the three age groups. Conclusions Five-year results show an excellent recipient survival and graft survival, especially in the youngest age group. Death with functioning graft is the leading cause of graft loss in patients >40 years. Early improvement of renal function and proteinuria together with strict control of cardiovascular risk factors are mandatory.

Lumbar bone mineral density in renal transplant patients on neoral and tacrolimus: a four-year prospective study.

Background. This prospective study was designed to investigate the long-term evolution of bone mineral density (BMD) in kidney transplant recipients. Methods. In 86 patients with functioning grafts, 65 on tacrolimus-based immunosuppression and 21 on cyclosporine-based immunosuppression, laboratory parameters and BMD measurements in lumbar spine (L2–L4) and femoral neck (FN) were performed by DEXA in the first month after transplantation (baseline) and yearly thereafter up to the fourth year. Results. BMD did not change at 12 months in lumbar spine nor in the FN. Detailed analysis identified three patterns of BMD in lumbar spine at 12 months: BMD remained stable in 27 patients (31.4%), decreased >2% in 31 (36.0%) and increased >2% in 28 (32.6%). Patients with no change or gain presented a parallel increase of BMD in FN (P<0.001 in both groups). On multivariate analysis, the variables associated with no change or lumbar BMD loss were total prednisone dose in grams at 12 months (OR 1.402; 95% CI 1.038–1.893; P=0.028), calcitriol levels at 12 months (OR 0.936; 95% CI 0.892–0.982; P=0.007) and lumbar BMD at baseline (OR 1.006; 95% CI 1.002–1.010; P=0.002). Late treatment with calcium supplements and calcitriol did not improve osteopenia. Conclusions. One third of patients had bone loss mainly during the first year of follow-up. Bone loss was associated to higher baseline BMD, high steroid dose, and lower calcitriol levels at 1 year. Late administration of calcitriol and calcium supplements did not improve posttransplant osteopenia. More than 50% of patients were osteopenic 4 years after transplantation.

Effect of hypertension before beginning dialysis on survival of hemodialysis patients

BACKGROUND The role of hypertension as a predictor of mortality in hemodialysis patients is controversial. The purpose of this study is to investigate the effect of hypertension before starting hemodialysis therapy on survival of patients without diabetes during renal replacement therapy. METHODS We reviewed 184 patients starting hemodialysis therapy. Variables studied were age, sex, renal disease, hypertension, comorbidity, vascular calcifications, left ventricular hypertrophy, body mass index, and albumin, cholesterol, and alkaline phosphatase levels. Regarding blood pressure control, three groups were considered: normotensive (NH), controlled hypertensive (c-HT), and uncontrolled hypertensive (uc-HT). RESULTS The Cox model was performed considering all-cause and cardiovascular mortality. The model was adjusted for age, sex, serum albumin level, vascular calcifications, history of hypertension, and comorbidity. Comorbidity included cardiovascular comorbidity. For all-cause mortality, comorbidity and history of uncontrolled hypertension were independent risk factors (comorbidity relative risk, 1.95; 95% confidence interval, 1.26 to 3.1; P = 0.003; uncontrolled hypertension relative risk, 1.79; 95% confidence interval, 1.15 to 2.8; P = 0.01). For cardiovascular mortality, uncontrolled hypertension was the main risk factor (relative risk, 2.93; 95% confidence interval, 1.68 to 5.12; P = 0.000). Mortality rates were 7.9/100 patient-years for NH, 8.7/100 patient-years for c-HT, and 14.1/100 patient-years for uc-HT patients. CONCLUSION This study suggests that uncontrolled hypertension in renal patients before starting dialysis therapy is a major risk factor for cardiovascular mortality during hemodialysis. Because hypertension usually starts in the initial stages of renal disease, we emphasize the importance of prompt and adequate control of blood pressure in this population.