Carlos Quereda

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.

Steroid withdrawal in renal transplant patients on triple therapy with a calcineurin inhibitor and mycophenolate mofetil: a meta-analysis of randomized, controlled trials.

Background. Two previous meta-analyses of randomized, controlled trials of steroid withdrawal after renal transplantation have shown significant increases in acute rejection (both analyses) and graft failure rates (the last analysis). A new examination of this topic including only randomized, controlled trials based on currently used, new, potent therapy with calcineurin inhibitors and mycophenolate mofetil (MMF), avoiding early trials with azathioprine, is justified. Methods. Steroid withdrawal in patients on triple therapy including a calcineurin inhibitor and MMF was assessed through meta-analysis of randomized, controlled trials in which intention-to-treat rates of acute rejection and renal allograft failure were established after steroid withdrawal or continuation. Results. Six trials were included, four in patients receiving cyclosporine and two in patients receiving tacrolimus. The risk ratio (RR) for acute rejection was 2.28 (95% confidence interval [CI], 1.65–3.16; P<0.00001) and the pooled risk difference (RD) was 0.08 (95% CI, 0.05–0.11; P<0.001), indicating that the proportion of patients with acute rejection after prednisone withdrawal was significantly higher compared with controls. The RR for graft failure was 0.73 (95% CI, 0.42–1.28; P=0.27) and the RD was −0.01 (95% CI, −0.03–0.01; P=0.28), indicating that the proportion of patients with graft failure after withdrawal was not significantly different from that observed in controls. Total cholesterol was significantly lower after steroid withdrawal (weighted mean difference, −0.53 &mgr;M (95% CI, −0.70 to −0.36; P<0.0001). Conclusions. Renal allograft recipients on triple therapy with a calcineurin inhibitor, MMF, and steroids are at low but significant risk of acute rejection after steroid withdrawal but do not suffer an increased risk of early graft failure. It is necessary to extend controlled follow-up to confirm graft function stabilization.

Long-Term Outcomes of IgA Nephropathy Presenting with Minimal or No Proteinuria

The long-term outcome of patients with IgA nephropathy who present with normal renal function, microscopic hematuria, and minimal or no proteinuria is not well described. Here, we studied 141 Caucasian patients with biopsy-proven IgA nephropathy who had minor abnormalities at presentation and a median follow-up of 108 months. None of the patients received corticosteroids or immunosuppressants. We reviewed renal biopsies using the Oxford classification criteria. In this sample, 46 (32%) patients had mesangial proliferation, whereas endocapillary proliferation, focal glomerulosclerosis, and tubulointerstitial abnormalities were uncommon. Serum creatinine increases >50% and >100% were observed in five (3.5%) patients and one (0.7%) patient, respectively; no patients developed ESRD. After 10, 15, and 20 years, 96.7%, 91.9%, and 91.9% of patients maintained serum creatinine values less than a 50% increase, respectively. Using Cox proportional hazards regression, the presence of segmental glomerulosclerosis was the only factor that significantly associated with a >50% increase in serum creatinine. Clinical remission occurred in 53 (37.5%) patients after a median of 48 months. Proteinuria>0.5 and >1.0 g/24 h developed in 21 (14.9%) and 6 (4.2%) patients, respectively. Median proteinuria at the end of follow-up was 0.1 g/24 h, with 41 (29.1%) patients having no proteinuria. At presentation, 23 (16.3%) patients were hypertensive compared with 30 (21.3%) patients at the end of follow-up; 59 (41.8%) patients were treated with renin-angiotensin blockers because of hypertension or increasing proteinuria. In summary, the long-term prognosis for Caucasian patients with IgA nephropathy who present with minor urinary abnormalities and normal renal function is excellent.

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.

Nephrogenic diabetes insipidus and renal tubular acidosis secondary to foscarnet therapy.

Foscarnet is used as therapy of cytomegalovirus (CMV) infection in immunosuppressed subjects. We present a patient with human immunodeficiency virus infection under treatment with foscarnet for CMV retinitis who complained of thirst and polyuria. Laboratory data showed hypernatremia with increased plasma osmolality and metabolic hyperchloremic acidosis. A water deprivation test demonstrated a nephrogenic diabetes insipidus. Other laboratory studies, including urine pH, anion gap, titratable acidity, and bicarbonate, showed a distal tubular acidification defect. All abnormalities were transient, with recovery a few days after foscarnet withdrawal. No cases of renal acidosis, and only one case of nephrogenic diabetes insipidus, has been previously reported as a complication of foscarnet treatment. Our patient developed both nephrogenic diabetes insipidus and renal tubular acidosis with a temporal pattern that demonstrated a link between foscarnet therapy and these abnormalities.

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.

Nonenzymatic Glycosylation of Hemoglobin and Total Plasmatic Proteins in End-Stage Renal Disease

In order to ascertain whether there are abnormalities of nonenzymatic glycosylation in uremia, the levels of nonenzymatically glycosylated hemoglobin (GHb), and total plasmatic glycosylated proteins (PGP) were studied using the thiobarbituric acid (TBA) method, a procedure not interfered with by carbamylation. Total hemoglobin A1 (HbA1) and the A1c fraction were also determined by ion exchange chromatographic methods. Sixty-six end-stage renal disease patients (29 nondiabetic and 8 diabetic uremic patients on conservative treatment, 29 nondiabetic hemodialysis patients) and 56 controls (32 nonuremic diabetic patients and 24 healthy controls) were studied. High levels of GHb and total PGP were found in the nondiabetic uremic group on conservative treatment with all the methods used, but the persistence of high chromatographically determined HbA1 levels in hemodialysis patients contrasts with the results obtained with the other techniques, which showed lower values on hemodialysis. Nondiabetic uremic patients with abnormal oral glucose tolerance curves had significantly higher levels of TBA-determined GHb and PGP. Uremic diabetic patients had the highest glycosylation levels of all the studied groups. We conclude that there is an abnormal nonenzymatic glycosylation of proteins in uremia, independent of carbamylation reactions and partially corrected by hemodialysis.

Hemodialysis with Low-Temperature Dialysate: A Long-Term Experience

The effect of cool dialysate in hemodialysis (HD)-induced symptoms was studied in a group of 8 patients, neither diabetic nor anephric, with a high incidence of HD-induced hypotension (20-90%). Patients were studied during two consecutive periods of 6 months, the first one with dialysate at 37 degrees C (598 sessions) and the second one at 35 degrees C (599 sessions). Dialysis at low temperature was associated with a decrease in symptomatic hypotension (SH) (47.4 vs. 33.9%, p less than 0.001), a greater loss of weight during HD (1.52 +/- 0.03 vs. 1.71 +/- 0.03 kg, p less than 0.001) and stabilization of predialysis systolic blood pressure (SBP) at a lower level (144 +/- 0.69 vs. 139 +/- 0.98 mm Hg, p less than 0.001). At 37 degrees C, SH was associated with a higher ultrafiltration (1.71 +/- 0.05 vs. 1.32 +/- 0.05 kg, p less than 0.001). There was an improvement of symptoms both taken as a whole (55.6 vs. 45.8%, p less than 0.01) or one by one, cramps were the only exception as they increased at 35 degrees C (2.7 vs. 10.9%, p less than 0.001) being related with a greater weight loss at both temperatures (1.47 +/- 0.04 vs. 2.04 +/- 0.25 kg at 37 degrees C, p less than 0.001; 1.76 +/- 0.03 kg vs. 2.23 = 0.10 kg at 35 degrees C, p less than 0.001). In spite of the increase in the frequency of cramps, 7 out of 8 patients experienced some amelioration of dialysis symptoms (range between 7 and 21.4%).(ABSTRACT TRUNCATED AT 250 WORDS)

Hypertension in primary chronic glomerulonephritis: analysis of 288 biopsied patients

The prevalence of hypertension in 288 patients with primary chronic glomerulonephritis was compared with that observed in a control group of 3,477 subjects from the same geographic area. 23.3% of the patients and 12.8% of the general population were hypertensive (p less than 0.01). However, if only patients with normal renal function were considered, prevalence of hypertension (12.7%) was not higher than in the control group. Hypertension was more frequent in focal segmental sclerosis (30%) and in membranous glomerulonephritis (26%) than in IgA nephropathy (9%), membranoproliferative glomerulonephritis (11%) and IgM mesangial glomerulonephritis (12%). Five years after renal biopsy, 92% of normotensive and 47% of hypertensive patients remained with normal renal function (p less than 0.001). These findings suggest that the high prevalence of hypertension in chronic glomerulonephritis is related to the declining renal function. On the other hand, hypertension appears to represent a bad prognostic sign.

Clinical Significance of IgM Mesangial Deposits in the Nephrotic Syndrome

We have studied 32 patients with idiopathic nephrotic syndrome aged from 3 to 59 years. The clinical course of 20 patients with IgM mesangial deposits was compared with that of 12 patients without glomerular immune deposits. The presence of IgM deposits seems to be unrelated to any particular clinical onset, histological pattern on light microscopy, therapy response, or clinical course in our relatively short follow-up. The conclusion from this study is that IgM mesangial deposition is not a marker for response to therapy in patients with idiopathic nephrotic syndrome.