L. Orofino

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.

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.

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)

Kidney transplantation in systemic lupus erythematosus nephritis: a one-center experience.

Eight patients with end-stage renal disease secondary to systemic lupus erythematosus (SLE) received 8 cadaveric renal allograft. Patient and graft survival was 100 and 87%, respectively. None of them showed extrarenal manifestations of SLE or recurrence of lupus nephritis after grafting. One graft was lost because of chronic rejection. In another patient, an episode of graft function deterioration due to bad control of arterial hypertension was observed. Three patients were transplanted during their first year on hemodialysis. Two women became pregnant after successful kidney transplantation; one suffered a spontaneous abortion and the other had a successful delivery. In neither of them, was SLE observed during or after pregnancy. Morbidity was low in this series, and infections were the most frequent complication. In summary, our experience with renal transplantation in SLE patients compares, favorably with the general nodiabetic transplanted population.

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.

EVIDENCE THAT ADDITION OF AZATHIOPRINE IMPROVES RENAL FUNCTION IN CYCLOSPORINE-TREATED PATIENTS WITH ALLOGRAFT DYSFUNCTION

Several approaches have been attempted to manage renal allograft dysfunction in cyclosporine-prednisone (CsA-Pred)-treated patients. Conversion to conventional therapy and perioperative triple drug have been associated with high rates of acute rejection episodes, infections, or neoplasms. We report our experience in delayed addition of azathioprine (1-2 mg/kg/day) to CsA/Pred protocol in three groups of patients. Group I (n = 9) had chronic renal function deterioration due to chronic rejection; group II (n = 10) had repeated or severe acute rejection episodes despite adequate CsA levels; and group III (n = 8) had CsA toxicity despite drug tapering. In group I, serum creatinine (SCr) had risen from 2.2 +/- 0.9 to 2.9 +/- 0.7 mg/dl over the 6 months prior to Aza addition (P less than 0.05), renal function declining at a rate of -0.14 +/- 0.12 Cr-1/year. In the 6-month post-Aza, renal function improved at a rate of 0.06 +/- 0.06 Cr-1/year and during the entire follow-up at a rate of 0.04 +/- 0.12 Cr-1/year (P less than 0.05) with stable CsA levels (288 +/- 167 vs. 251 +/- 172 ng/dl, NS). In group II response was worse, though the rate of declining renal function prior to Aza (-0.10 +/- 0.10 Cr-1/year) was almost stopped after Aza. In group III there was very good response to Aza addition, as 7 out of 8 patients improved graft function (baseline SCr 2.5 +/- 0.7 mg/dl vs. 1.9 +/- 0.6 mg/dl at last follow-up, P less than 0.05), with significantly decreased CsA levels (480 +/- 97 vs. 268 +/- 120, P less than 0.05). One patient from group II died from pneumonia, and 6 patients (1 from group I and 5 from group II) lost their grafts. Fifteen patients improved graft function, and 9 worsened after addition of Aza. The bad-responders had significantly higher SCr at baseline compared with the good-responders (3.8 +/- 1.8 vs. 2.7 +/- 0.6 mg/dl, P less than 0.01). Amelioration of chronic graft dysfunction can be achieved by delayed addition of Aza to CsA-Pred in patients with chronic rejection or CsA toxicity. This is accompanied by low rate of acute rejection, good patient and graft survival, and low rate of infections. A worse outcome can be seen in patients with high-baseline SCr levels, suggesting the need for addition of Aza in the initial chronic graft dysfunction.

Hepatitis C Antibody after Kidney Transplantation: Clinical Significance

The prevalence of antibodies to hepatitis C virus (HCV) was investigated in 231 renal transplantation recipients, by a first- and second-generation EIA assay and a second-generation immunoblot assay (4-RIBA). Before transplantation, prevalence of anti-HCV was 22.6% and was related to the time on dialysis (p < 0.01), transfusions (p < 0.01) and previous history of chronic liver disease (p < 0.01. Following transplantation, 32 patients (13.9%) were anti-HCV positive by the first-generation enzyme immunoassay (EIA) and it increased to 57 patients (24.7%) when anti-HCV was measured by the second-generation EIA. The 4-RIBA assay confirmed the positivity in 46 patients (80.7%), 11 patients (19.3%) were indeterminate. Seroconversion after grafting was observed in 7 negative patients, and another 7 patients became negative after the procedure. The presence of anti-HCV antibody after transplantation was determined by the patient status on dialysis, 80% of them being positive before surgery. Twenty-one 4-RIBA-positive transplantation patients (45.7%) had persistently or intermittently abnormalities on liver function tests, suggesting chronic liver disease. A liver biopsy performed on 10 of these patients showed; chronic active hepatitis in 6, chronic persistent hepatitis in 2, and chronic lobular hepatitis in the other 2 patients. Another 23 4-RIBA-positive transplantation patients had normal alanine aminotransferase levels despite long follow-up (66.2 +/- 32.2 months). The prevalence of anti-HCV antibody can be underestimated if the antibody is measured by first-generation EIA alone. About 50% of patients with anti-HCV had chronic liver disease, and the histological findings suggested a possible evolution to cirrhosis.(ABSTRACT TRUNCATED AT 250 WORDS)

Treatment of Secondary Hyperparathyroidism in Hemodialyzed Patients with High-Dose Calcium Carbonate without Vitamin D3 Supplements

Background: Vitamin D compounds are usually indicated for the treatment of secondary hyperparathyroidism in dialysis patients. The possibility to induce a reversal of hyperparathyroidism with calcium supplementation alone is controversial. The present study was conducted to assess if oral calcium carbonate may constitute a therapeutic option for the control of hyperparathyroidism in patients with high PTH concentrations at the beginning of the treatment with chronic hemodialysis. Methods: Thirty-one patients with end-stage renal failure with an intact PTH concentration above 250 pg/ml at the beginning of chronic hemodialysis therapy were treated with high doses of calcium carbonate; no patient received either aluminium-containing binders or vitamin D compounds. To minimize hypercalcemia, a calcium dialysate concentration of 2.5 mEq/l was used in all patients. The goal of the study was to reduce the intact PTH concentration to 250 pg/ml with oral calcium carbonate supplements alone. Results: Throughout the first year on hemodialysis treatment, the intact PTH concentration decreased from 538 ± 256 to 251 ± 218 pg/ml (p < 0.001). By the end of the study, the therapeutic objective was achieved in 22 patients (71%) (‘responder’ group). The remaining 9 patients were classified as the ‘treatment failure’ group. The basal intact PTH concentration was not different between both groups (508 ± 235 vs. 612 ± 303 pg/ml, respectively, p = n.s.), but 5 ‘treatment failure’ patients admitted to take a dose of calcium carbonate lower than that prescribed. There were 40 episodes of hyperphosphatemia (11% of all measurements) in 7 of 31 patients, 5 of them belonged to the noncompliance ‘treatment failure’ patients. Only 15 episodes (4% of all measurements) of transient hypercalcemia (range 11.1 – 11.9 mg/dl) were detected in 8 patients. Conclusions: Secondary hyperparathyroidism in hemodialysis patients can often be reverted by oral calcium carbonate alone. But a good adherence to treatment is absolutely necessary.

Acute renal failure in the elderly

The prevalence of acute renal failure (ARF) in the elderly is much greater than in the general population. Important structural and functional changes are present in the aging kidneys and predispose the elderly patient to multiple types of acute renal disease. Prerenal failure, hemodynamically-mediated acute tubular necrosis, nephrotoxic ARF, ARF of vascular origin and obstructive ARF are of special importance in the geriatric population. In the present review we analyze some aspects of interest for the nephrologist and urologist regarding diagnosis and management of these severe but often reversible diseases. Elderly patients with ARF appear to have a moderately worse prognosis than younger patients, but age should not be used as a discriminant factor in therapeutic decisions concerning ARF. Instead, early clinical features such as hypotension, assisted respiration or coma are decidedly related to mortality in ARF patients of any age. Although elderly patients who survive after an ARF episode appear to need more time for total recovery and exhibit a lower level of renal function than younger survivors, long-term prognosis is quite good.