Complications of surgical treatment of cervical carcinoma

A total of 302 patients with stage Ib and IIa cervical carcinoma were submitted to radical hysterectomy and lymphadenectomy during the period from 1980 to 1994. The morbidity rate was 37.5% and the mortality rate 0.6%. The most common intraoperative complications were injuries to the great pelvic vessels and the most frequent postoperative complications involved the urinary tract. The leading causes of morbidity were urinary infection (20.8%), bladder dysfunction (9.2%) and ureteral fistulas (2.9%). Although the rate of complications was high, morbidity has been decreasing over the last five years. Thus, radical hysterectomy continues to be one of the methods for the treatment of early cervical carcinoma that presents an acceptable 5-year survival rate.

Influence of first morning urine volume, fasting blood glucose and glycosylated hemoglobin on first morning urinary albumin concentration

The aim of the present study was to evaluate the effect of first morning urinary volume (collected on three different non-consecutive days), fasting blood glucose (determined on the first and third days of urine collection), and glycosylated hemoglobin (determined on the first and third days of urine collection) on the albumin concentration in first morning urine samples collected on three different days. We found 3.6% asymptomatic bacteriuria in the urine samples; therefore, every urine sample must be tested to exclude infection. One hundred and fifty urine samples were provided by 50 IDDM patients aged 21.9 ± 7 (12-38) years with a disease duration of 6.8 ± 5.8 (0.4-31) years attending the Diabetes Clinic at the State University Hospital of Rio de Janeiro. There were no differences in albumin concentration (6.1 vs 5.8 vs 6.2 µg/ml; P = NS) or urinary volume (222.5 vs 210 vs 200 ml) between the three samples. In addition, there were no differences in fasting blood glucose (181.9 ± 93.6 vs 194.6 ± 104.7 mg%; P = NS) or glycosylated hemoglobin (HbA1)(8.4 ± 1.3 vs 8.8 ± 1.5%; P = NS) between the first and third blood samples. Six patients (group 1) had a mean urinary albumin concentration of more than 20 µg/ml for the three urine samples. This group was compared with the 44 patients (group 2) with a mean urinary albumin concentration for the three urine samples of less than 20 µg/ml. No difference was found between groups 1 and 2 in relation to fasting blood glucose (207.1 ± 71.7 vs 187.6 ± 84.6 mg/dl), HbA1 (8.1 ± 0.9 vs 8.6 ± 1.1%) or urinary volume [202 (48.3-435) vs 246 (77.3-683.3) ml]. Stepwise multiple regression analysis with albumin concentration of first morning urine samples as the dependent variable, and urinary volume, fasting blood glucose and glycosylated hemoglobin as independent variables, showed that only 12% (P = 0.01) of the albumin concentration could be accounted for by the independent effect of morning urine volume on the first day of urine collection. No urine samples showed a change in the cutoff level of 20 µg/ml of albumin concentration as the result of volume. Fasting blood glucose and glycosylated hemoglobin did not influence the urinary albumin concentration. Considerable variability in urinary albumin concentration was found in the three morning urine samples with a mean intraindividual coefficient variation of 56%. In conclusion, in the present study, urinary volume had a minimal, though not constant, effect on first morning urinary albumin concentration. Day-to-day metabolic and clinical control of IDDM patients, except probably for ketoacidosis, should not contraindicate microalbuminuria screening in first morning urine samples

An experimental model for the measurement of renal function after temporary ureteral obstruction in the rat

We present the results obtained with a ureterovesical implant after ipsilateral ureteral obstruction in the rat, suitable for the study of renal function after deobstruction in these animals. Thirty-seven male Wistar rats weighing 260 to 300 g were submitted to distal right ureteral ligation and divided into 3 groups, A (N = 13, 1 week of obstruction), B (N = 14, 2 weeks of obstruction) and C (N = 10, 3 weeks of obstruction). The animals were then submitted to ureterovesical implantation on the right side and nephrectomy on the left side. During the 4-week follow-up period serum levels of urea and creatinine were measured on the 2nd, 7th, 14th, 21st and 28th day and compared with preoperative levels. The ureterovesical implantation included a psoas hitch procedure and the ureter was pulled into the bladder using a transvesical suture. During the first week of the postoperative period 8 animals died, 4/13 in group A (1 week of obstruction) and 4/14 in group B (2 weeks of obstruction). When compared to preoperative serum levels, urea and creatinine showed a significant increase (P<0.05) on the 2nd postoperative day in groups A and B, with a gradual return to lower levels. However, the values in group B animals were higher than those in group A at the end of the follow-up. In group C, 2/10 animals (after 3 weeks of obstruction) were sacrificed at the time of ureterovesical implantation due to infection of the obstructed kidneys. The remaining animals in this group were operated upon but all of them died during the first week of follow-up due to renal failure. This technique of ureterovesical implantation in the rat provides effective drainage of the upper urinary tract, permitting the development of an experimental model for the study of long-term renal function after a period of ureteral obstruction

Effect of thyroparathyroidectomy on urinary acidification in diabetic rats

In previous studies we have shown stimulation of renal acid excretion in the proximal tubules of rats with diabetes of short duration, with no important alterations in glomerular hemodynamics; on the other hand, in thyroparathyroidectomized rats (TPTX model), a significant decrease in renal acid excretion, glomerular filtration rate (GFR) and renal plasma flow (RPF) was detected. Since important changes in the parathyroid hormone-vitamin D-Ca axis are observed in the diabetic state, the present study was undertaken to investigate the renal repercussions of thyroparathyroidectomy in rats previously made diabetic by streptozotocin (45 mg/kg). Four to 6 days after the induction of diabetes (DM), a group of rats were thyroparathyroidectomized (DM + TPTX). Renal functional parameters were evaluated by measuring the inulin and sodium para-aminohippurate clearance on the tenth day. The decrease in the GFR and RPF observed in TPTX was not reversed by diabetes since the same alterations were observed in DM + TPTX. Net acid (NA) excretion was unchanged in DM (6.19 ± 0.54), decreased in TPTX (3.76 ± 0.25) and returned to normal levels in DM + TPTX (5.54 ± 0.72) when compared to the control group (6.34 ± 0.14 µmol min-1 kg-1). The results suggest that PTH plays an important vasodilator role regarding glomerular hemodynamics, since in its absence the impairment in GFR and RPF was not reversed by the diabetic state. However, with respect to acid excretion, the presence of diabetes was able to overcome the negative stimulus represented by TPTX.

Urinary secretory IgA after nutritional rehabilitation

We studied the secretory IgA (sIgA) response of the mucosal urinary tract of malnourished children before and after nutritional rehabilitation. sIgA concentration (mg/l) was determined by ELISA in 187 children aged 3 months to 5 years. The children, who frequented a day care center, were divided into four groups, according to nutritional status: 57 were eutrophic, 49 were undergrown, 57 were moderately malnourished and 24 were severely malnourished. In addition, dip slide (Urotube, Roche) and dip-stick (Combur 9-Boehringer) tests showed that children had no bacteriuria or any other urinary abnormalities. Plasma albumin concentration (g/dl) was significantly lower (P<0.005) in the severely malnourished group (mean 3.0 ± 0.3 SD) than in the eutrophic group (mean 4.0 ± 0.5 SD). When each nutritional state was analyzed, no significant differences in the sIgA were found between the 0 |-| 1 and 1 -| 5 year age range. In the moderately and severely malnourished groups, sIgA (0.36 and 0.45, respectively) was significantly lower than in the eutrophic (0.69) and undergrown (0.75) groups. Ninety-five children were included in the 8-month follow-up study; 30 children were excluded from the follow-up because 4 had bacteriuria, 11 had leukocyturia, 8 had proteinuria and 7 had hematuria. Among the malnourished children, 40% showed nutritional improvement (P<0.05) and significantly increased sIgA as compared to reference values for the eutrophic and undergrown groups. These data suggest that malnourished children have a significantly lower urinary sIgA than eutrophic children. After nutritional rehabilitation, they develop local immunity with a significant increase in sIgA.

Study of urinary acidification in patients with idiopathic hypocitraturia

Hypocitraturia (HCit) is one of the most remarkable features of renal tubular acidosis, but an acidification defect is not seen in the majority of hypocitraturic patients, whose disease is denoted idiopathic hypocitraturia. In order to assess the integrity of urinary acidification mechanisms in hypocitraturic idiopathic calcium stone formers, we studied two groups of patients, hypocitraturic (HCit, N = 21, 39.5 ± 11.5 years, 11 females and 10 males) and normocitraturic (NCit, N = 23, 40.2 ± 11.7 years, 16 females and 7 males) subjects, during a short ammonium chloride loading test lasting 8 h. During the baseline period HCit patients showed significantly higher levels of titratable acid (TA). After the administration of ammonium chloride, mean urinary pH (3rd to 8th hour) and TA and ammonium excretion did not differ significantly between groups. Conversely, during the first hour mean urinary pH was lower and TA and ammonium excretion was higher in HCit. The enhanced TA excretion by HCit during the baseline period and during the first hour suggests that the phosphate buffer mechanism is activated. The earlier response in ammonium excretion by HCit further supports other evidence that acidification mechanisms react promptly. The present results suggest that in the course of lithiasic disease, hypocitraturia coexists with subtle changes in the excretion of hydrogen ions in basal situations.

Familial predisposition to hypertension and the association between urinary sodium excretion and blood pressure in a population-based sample of young adults

The reasons for the inconsistent association between salt consumption and blood pressure levels observed in within-society surveys are not known. A total of 157 normotensive subjects aged 18 to 35 years, selected at random in a cross-sectional population-based survey, answered a structured questionnaire. They were classified as strongly predisposed to hypertension when two or more first-degree relatives had a diagnosis of hypertension. Anthropometric parameters were obtained and sitting blood pressure was determined with aneroid sphygmomanometers. Sodium and potassium excretion was measured by flame spectrophotometry in an overnight urine sample. A positive correlation between blood pressure and urinary sodium excretion was detected only in the group of individuals strongly predisposed to hypertension, both for systolic blood pressure (r = 0.51, P<0.01) and diastolic blood pressure (r = 0.50, P<0.01). In a covariance analysis, after controlling for age, skin color and body mass index, individuals strongly predisposed to hypertension who excreted amounts of sodium above the median of the entire sample had higher systolic and diastolic blood pressure than subjects classified into the remaining conditions. The influence of familial predisposition to hypertension on the association between salt intake and blood pressure may be an additional explanation for the weak association between urinary sodium excretion and blood pressure observed in within-population studies, since it can influence the association between salt consumption and blood pressure in some but not all inhabitants.

Scintigraphy and Doppler ultrasonography for the evaluation of obstructive urinary calculi

Forty-seven patients with unilateral obstructive calculi (12 males and 35 females) were submitted to 99mTc-diethylene triamine pentaacetic acid (DTPA) or 99mTc-dimercaptosuccinic acid (DMSA) scans for assessment of renal function. The scans revealed unilateral functional deficit in 68 and 66% of the patients, respectively. A calculus size of 1.1 to 2.0 cm was significantly associated with deficit detected by DTPA, but duration of obstruction and calculus localization were not. After relief of the obstruction, the mean percent renal function of the affected kidney was found to be significantly increased from 25 ± 12% to 29 ± 12% in DTPA and from 21 ± 15% to 24 ± 12% in DMSA. Initial Doppler ultrasonography performed in 35 patients detected an increased resistive index in 10 (29%). In the remaining patients with a normal resistive index, ureteral urinary jet was observed, indicating partial obstruction. The high frequency of renal function impairment detected by DTPA and of tubulointerstitial damage detected by DMSA as well as the slight amelioration of unilateral renal function after relief of obstruction suggest that scintigraphy assessment may help evaluate the unilateral percentage of renal function and monitor renal function recovery when it occurs. The presence of a urinary jet detected by Doppler ultrasonography further indicates the severity of obstruction and the recovery prognosis.

Comparison of methods for urinary albumin determination in patients with type 1 diabetes

We tested the correlation of the albumin-to-creatinine ratio (A/C) in an early-morning urine sample, measured with a commercial kit (DCA 2000®), with the conventional immunoturbidimetric determination in the laboratory and with overnight albumin excretion rate (reference method). Fifty-five type 1 diabetic adolescents had their first-morning urine collected on the 1st and 8th day of the period. Urinary albumin and creatinine were determined immediately using the DCA 2000® kit. Samples were also stored for laboratory analysis. To evaluate the correlation between early-morning urinary A/C ratio and overnight albumin excretion rate, 16 subjects had a timed overnight urine collection. A/C ratios determined with the DCA 2000® kit and by the laboratory method were 13.1 ± 20.5 and 20.4 ± 46.3 mg/g, respectively. A/C results by both methods proved to be strongly correlated (r = 0.98, P<0.001). DCA 2000®-determined A/C showed 50% sensitivity and 100% specificity when compared to the reference method. Spot urinary A/C of the subset of 16 subjects significantly correlated with their overnight albumin excretion rate (r = 0.98, P<0.001). Intraindividual variation ranged from 17 to 32% and from 9 to 63% for A/C and overnight albumin excretion rate, respectively. In conclusion, an early-morning specimen should be used instead of timed overnight urine and the A/C ratio is an accurate, reliable and easily determined parameter for the screening of diabetic nephropathy. Immediate measurement of the A/C ratio is feasible using the DCA 2000® kit. Intraindividual variability indicates the need for repeated determinations to confirm microalbuminuria and the diagnosis of incipient diabetic nephropathy.

Effect of calcium intake on urinary oxalate excretion in calcium stone-forming patients

Dietary calcium lowers the risk of nephrolithiasis due to a decreased absorption of dietary oxalate that is bound by intestinal calcium. The aim of the present study was to evaluate oxaluria in normocalciuric and hypercalciuric lithiasic patients under different calcium intake. Fifty patients (26 females and 24 males, 41 ± 10 years old), whose 4-day dietary records revealed a regular low calcium intake (<=500 mg/day), received an oral calcium load (1 g/day) for 7 days. A 24-h urine was obtained before and after load and according to the calciuria under both diets, patients were considered as normocalciuric (NC, N = 15), diet-dependent hypercalciuric (DDHC, N = 9) or diet-independent hypercalciuric (DIHC, N = 26). On regular diet, mean oxaluria was 30 ± 14 mg/24 h for all patients. The 7-day calcium load induced a significant decrease in mean oxaluria compared to the regular diet in NC and DIHC (20 ± 12 vs 26 ± 7 and 27 ± 18 vs 32 ± 15 mg/24 h, respectively, P<0.05) but not in DDHC patients (22 ± 10 vs 23 ± 5 mg/24 h). The lack of an oxalate decrease among DDHC patients after the calcium load might have been due to higher calcium absorption under higher calcium supply, with a consequent lower amount of calcium left in the intestine to bind with oxalate. These data suggest that a long-lasting regular calcium consumption <500 mg was not associated with high oxaluria and that a subpopulation of hypercalciuric patients who presented a higher intestinal calcium absorption (DDHC) tended to hyperabsorb oxalate as well, so that oxaluria did not change under different calcium intake.

Urinary iron excretion induced by intravenous infusion of deferoxamine in ß-thalassemia homozygous patients

The purpose of the present study was to identify noninvasive methods to evaluate the severity of iron overload in transfusion-dependent ß-thalassemia and the efficiency of intensive intravenous therapy as an additional tool for the treatment of iron-overloaded patients. Iron overload was evaluated for 26 ß-thalassemia homozygous patients, and 14 of them were submitted to intensive chelation therapy with high doses of intravenous deferoxamine (DF). Patients were classified into six groups of increasing clinical severity and were divided into compliant and non-compliant patients depending on their adherence to chronic chelation treatment. Several methods were used as indicators of iron overload. Total gain of transfusion iron, plasma ferritin, and urinary iron excretion in response to 20 to 60 mg/day subcutaneous DF for 8 to 12 h daily are useful to identify iron overload; however, urinary iron excretion in response to 9 g intravenous DF over 24 h and the increase of urinary iron excretion induced by high doses of the chelator are more reliable to identify different degrees of iron overload because of their correlation with the clinical grades of secondary hemochromatosis and the significant differences observed between the groups of compliant and non-compliant patients. Finally, the use of 3-9 g intravenous DF for 6-12 days led to a urinary iron excretion corresponding to 4.1 to 22.4% of the annual transfusion iron gain. Therefore, continuous intravenous DF at high doses may be an additional treatment for these patients, as a complement to the regular subcutaneous infusion at home, but requires individual planning and close monitoring of adverse reactions.

Effect of intracerebroventricularly injected insulin on urinary sodium excretion by cerebroventricular streptozotocin-treated rats

Recent evidence suggests that insulin may influence many brain functions. It is known that intracerebroventricular (icv) injection of nondiabetogenic doses of streptozotocin (STZ) can damage insulin receptor signal transduction. In the present study, we examined the functional damage to the brain insulin receptors on central mechanisms regulating glomerular filtration rate and urinary sodium excretion, over four periods of 30 min, in response to 3 µl insulin or 0.15 NaCl (vehicle) injected icv in STZ-treated freely moving Wistar-Hannover rats (250-300 g). The icv cannula site was visually confirmed by 2% Evans blue infusion. Centrally administered insulin (42.0 ng/µl) increased the urinary output of sodium (from 855.6 ± 85.1 to 2055 ± 310.6 delta%/min; N = 11) and potassium (from 460.4 ± 100 to 669 ± 60.8 delta%/min; N = 11). The urinary sodium excretion response to icv insulin microinjection was markedly attenuated by previous central STZ (100 µg/3 µl) administration (from 628 ± 45.8 to 617 ± 87.6 delta%/min; N = 5) or by icv injection of a dopamine antagonist, haloperidol (4 µg/3 µl) (from 498 ± 39.4 to 517 ± 73.2 delta%/min; N = 5). Additionally, insulin-induced natriuresis occurred by increased post-proximal tubule sodium rejection, despite an unchanged glomerular filtration rate. Excluding the possibility of a direct action of STZ on central insulin receptor-carrying neurons, the current data suggest that the insulin-sensitive response may be processed through dopaminergic D1 receptors containing neuronal pathways.

Urinary NO3 excretion and renal failure in indinavir-treated patients

Treatment with indinavir (IDV), a protease inhibitor, is frequently associated with renal abnormalities. We determined the incidence of renal failure (creatinine clearance <80 mL min-1 1.73 (m²)-1) in HIV patients treated with highly active antiretroviral therapy, including IDV, and investigated the possible mechanisms and risk factors of IDV nephrotoxicity. Thirty-six patients receiving IDV were followed for 3 years. All were assessed for age, body weight, duration of infection, duration of IDV treatment, sulfur-derivative use, total cholesterol, triglycerides, magnesium, sodium, potassium, creatinine, and urinalysis. We also determined renal function in terms of creatinine clearance, urine osmolality and fractional excretion of sodium, potassium, and water. Urinary nitrate (NO3) excretion was measured in 18 IDV-treated patients and compared with that of 8 patients treated with efavirenz, a drug without renal side effects. Sterile leukocyturia occurred in 80.5% of the IDV-treated patients. Creatinine clearance <80 mL min-1 1.73 (m²)-1 was observed in 22 patients (61%) and was associated with low body weight and the use of sulfur-derivatives. These patients also had lower osmolality, lower urine volume and a higher fractional excretion of water compared to the normal renal function group. Urinary NO3 excretion was significantly lower in IDV-treated patients (809 ± 181 µM NO3-/mg creatinine) than in efavirenz-treated patients (2247 ± 648 µM NO3-/mg creatinine, P < 0.01). The lower NO3 excretion suggests that IDV decreases nitric oxide production.

Determination of renal function in long-term heart transplant patients by measurement of urinary retinol-binding protein levels

Significant improvements have been noted in heart transplantation with the advent of cyclosporine. However, cyclosporine use is associated with significant side effects, such as chronic renal failure. We were interested in evaluating the incidence of long-term renal dysfunction in heart transplant recipients. Fifty-three heart transplant recipients were enrolled in the study. Forty-three patients completed the entire evaluation and follow-up. Glomerular (serum creatinine, creatinine clearance measured, and creatinine clearance calculated) and tubular functions (urinary retinol-binding protein, uRBP) were re-analyzed after 18 months. At the enrollment time, the prevalence of renal failure ranged from 37.7 to 54% according to criteria used to define it (serum creatinine > or = 1.5 mg/dL and creatinine clearance <60 mL/min). Mean serum creatinine was 1.61 ± 1.31 mg/dL (range 0.7 to 9.8 mg/dL) and calculated and measured creatinine clearances were 67.7 ± 25.9 and 61.18 ± 25.04 mL min-1 (1.73 m²)-1, respectively. Sixteen of the 43 patients who completed the follow-up (37.2%) had tubular dysfunction detected by increased levels of uRBP (median 1.06, 0.412-6.396 mg/dL). Eleven of the 16 patients (68.7%) with elevated uRBP had poorer renal function after 18 months of follow-up, compared with only eight of the 27 patients (29.6%) with normal uRBP (RR = 3.47, P = 0.0095). Interestingly, cyclosporine trough levels were not different between patients with or without tubular and glomerular dysfunction. Renal function impairment is common after heart transplantation. Tubular dysfunction, assessed by uRBP, correlates with a worsening of glomerular filtration and can be a useful tool for early detection of renal dysfunction.

A model of hemorrhagic cystitis induced with acrolein in mice

Acrolein is a urinary metabolite of cyclophosphamide and ifosfamide, which has been reported to be the causative agent of hemorrhagic cystitis induced by these compounds. A direct cytotoxic effect of acrolein, however, has not yet been demonstrated. In the present study, the effects of intravesical injection of acrolein and mesna, the classical acrolein chemical inhibitor, were evaluated. Male Swiss mice weighing 25 to 35 g (N = 6 per group) received saline or acrolein (25, 75, 225 µg) intravesically 3, 6, 12, and 24 h before sacrifice for evaluation of bladder wet weight, macroscopic and histopathological changes by Gray's criteria, and 3 and 24 h for assessment of increase in vascular permeability. In other animals, mesna was administered intravesically (2 mg) or systemically (80 mg/kg) 1 h before acrolein. Intravesical administration of acrolein induced a dose- and time-dependent increase in vascular permeability and bladder wet weight (within 3 h: 2.2- and 21-fold increases in bladder wet weight and Evans blue dye exuded, respectively, at doses of 75 µg/bladder), as confirmed by Gray's criteria. Pretreatment with mesna (2-mercaptoethanesulfonic acid), which interacts with acrolein resulting in an inactive compound, inhibited all changes induced by acrolein. Our results are the first demonstration that intravesical administration of acrolein induces hemorrhagic cystitis. This model of acrolein-induced hemorrhagic cystitis in mice may be an important tool for the evaluation of the mechanism by which acrolein induces bladder lesion, as well as for investigation of new uroprotective drugs.