Luis Orte

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.

Veno-Occlusive Hepatic Disease of the Liver in Renal Transplantation: Is Azathioprine the Cause?

Five male patients with veno-occlusive disease of the liver (VOD) were observed in 200 consecutive renal transplants (RT) treated with azathioprine and prednisone. Mild liver enzymatic increases not justified by other reasons were detected between 2 and 9 months after RT. All 5 patients developed portal hypertension and died between 18 and 79 months following RT. Diagnosis of VOD was histological; in 3 cases diagnosis was made while the patients were still alive. In our patients, 9 previous viral hepatotropic infections (5 during hemodialysis and 4 after TR) were demonstrated. Due to the reported low incidence of VOD in RT patients, when many of them have been treated with azathioprine, the etiological role of this drug must be questioned. However, the possible association of a previous hepatotropic viral infection and the use of an immunosuppressive agent should be considered as a probable cause of VOD in kidney grafts.

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.

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.

Influence of Hypertension on Early Renal Insufficiency in Autosomal Dominant Polycystic Kidney Disease

To determine the potential effect of hypertension on early renal function deterioration, 30 patients (13 normotensive and 17 hypertensive) with autosomal dominant polycystic kidney disease and initially normal renal function were retrospectively analyzed. The decline in renal function was estimated by the slope of the linear regression of creatinine clearance versus time. Analysis was made in terms of standardized slope (slope divided by its standard deviation, i.e., measured in standard deviation units). In the hypertensive group the mean standardized slope was significantly higher than in the normotensive group (-10.89 and -4.98, respectively; p < 0.001). The average mean arterial pressure was significantly lower in the normotensive group with respect to the hypertensive one (95 and 109 mm Hg, respectively; p < 0.0001). There was a significant negative linear relationship between the average values of systolic, diastolic, and mean arterial pressures and standardized slopes. The best prediction equation for renal function deterioration was obtained using a multiple linear regression model in which independent variables were maximum and average diastolic pressures. Therefore, prior to renal insufficiency, a high arterial pressure had a significant contribution to renal function deterioration.

Use of urinary parameters in the diagnosis of total acute renal artery occlusion.

Limited attention has been paid to the composition of the small amounts of urine that are frequently produced by patients with acute renal failure (ARF) of vascular origin. We have investigated the value of basic urinary parameters in the early diagnosis of total or partial acute renal artery occlusion (ARAO). We have reviewed the records of 30 patients with ARF: group 1 (n = 10) had total ARAO; group 2 (n = 10) had unilateral ARAO with a contralateral functioning kidney, and group 3 (n = 10) had hemodynamically mediated ARF subsequent to a major vascular abdominal surgical procedure, without arterial thrombosis. Serum sodium, potassium, urea, creatinine and osmolality, as well as urinary sodium, potassium, urea, creatinine and osmolality, were determined by standard techniques, and the fractional excretion of sodium (FENa) was calculated. Serum parameters were similar in all groups. Urinary sodium and FENa were higher in group 1 than in the other groups (p

Ventricular Ectopic Activity in Hemodialysis

C. Quereda, MD, Servicio de Nefrología, Centro Ramón Cajal, Carretera de Colmenar km 9,100, 28034 Madrid (España) Dear Sir, In an interesting study recently published in Nephron , Wizemann et al. [1] concluded that the incidence of ventricular arrhythmias in chronic hemodialysis (HD) patients is primarily dependent on the presence of preexisting coronary artery disease and that HD or related methods do not increase the risk of ventricular ectopics in patients without digitalis medication. The first conclusion is in agreement with our previously published work [2] in which we studied 22 HD patients with EKG Holier monitoring, 15 uremics before starting replacement therapy and 25 healthy normals. Our patients with complex arrhythmias had evidence of preexisting cardiopathy, which seemed to be the main predisposing factor. However, our data differ with respect to the ectopic activity induction by HD per se. We found that most complex arrhythmias, even in nondigitalized patients, develop during the last hours of HD or just thereafter. Nevertheless clinical (weight, cardiac rate, blood pressure) or analytical (serum urea, osmolality, potassium, calcium, phosphate, magnesium and bicarbonate) changes induced by HD were not different in patients with arrhythmias than in those without them. Recently, we have studied 35 HD patients with Holter monitoring [unpubl. data]. The number and percentage of patients with arrhythmias classified in 4-hour periods, according to the criteria of Lown and Graboys [3], before, during and after HD up to 24 h are recorded in table I. Ten patients (28%) showed complex arrhythmias (Lown grades II-V) during the registered time, and only 1 of them was on digitalis treatment. In 8 patients (80%) these arrhythmias were detected during HD or in the next 4-hour period, and as can be seen in table I, their incidence during these two intervals (23%) is much greater than in pre-HD (3%) or in later post-HD periods (6%) with a slight increase during sleep (8%). An important difference between our study and that of Wizemann et al. [1] is the stategy of monitoring: we included a basal 4-hour period before the HD session (after 72 h of last HD), a conventional 4-hour HD with acetate and cuprophan membrane, and a post-HD 16-hour period. On the contrary, in Wizeman ‘s work, the monitoring starts with HD, while the last 4 h are used as ‘pre-HD’ control. We found that although the greatest ectopic activity is coincident with the end of HD, it persisted for many hours in some patients. This fact and perhaps some differences in the population studied are probably the causes of this discrepancy. Table I. Ectopic ventricular activity in HD patients (n = 35)

Shape of the Relationship between Hypertension and the Rate of Progression of Renal Failure in Autosomal Dominant Polycystic Kidney Disease

The effect of hypertension on the rate of progression of renal failure was analyzed in 26 patients with autosomal dominant polycystic kidney disease relating the slopes of progression (linear regression of the reciprocal serum creatinine on time) with the average mean arterial pressure, systolic and diastolic pressure, derived over the entire follow-up period for each patient. Hypertension was found in 19 of the 26 patients. Using simple linear regression, there was no significant correlation between the two variables in any case. Using polynomial regression (quadratic and cubic), this relationship fits a sigmoid (for diastolic pressure) or a negative parabolic curve (for mean arterial pressure and systolic pressure); i.e. the lowest and the highest values of mean arterial pressure and systolic pressure were associated with faster rates of progression. Thus, an appropriate model to study this relationship is not the linear but the polynomial regression.

ANTIPROTEINURIC EFFECT OF CALCIUM ANTAGONISTS ON PUROMYCIN-INDUCED EXPERIMENTAL NEPHROSIS

Calcium antagonists have a potential for beneficial effects on kidney function unrelated to their antihypertensive action. In this study we have investigated the efficacy of calcium antagonists compounds (verapamil, nifedipine and diltiazem) on reversible acute renal insufficiency, proteinuria and interstitial nephritis induced by the puromycin ammo nucleoside (PAN). An increase in blood pressure (BP) was detected on day 14, with no statistical differences in the response to calcium antagonists. Serum creatinine concentration increased to 1.2 mg/dL on day 7 after PAN and decreased to 0.7 mg/dL at 14 days, calcium antagonists shortened the time required to reach baseline or control levels. Calcium antagonists also reduced proteinuria in the PAN-treated animals, in both day 7 and day 14. Differential effects of the antagonists were observed. Verapamil caused a greater reduction (p < 0.01) in proteinuria than nifedipine or diltiazem in day 7. Moreover, verapamil (p < 0.01) and nifedipine (p < 0.01) reduced the total number of interstitial infiltrating leukocytes from 690 to 120 and 425 positive cells/20 high power fields (× 63) respectively, by contrast, diltiazem had no effect. We conclude that in this model of PAN nephropathy verapamil is more effective in reducing both proteinuria and the severity of acute interstitial nephritis than either nifedipine or diltiazem. The possible clinical implications of these results remain to be elucidated.