Disposition of tobramycin in patients with cystic fibrosis: a prospective controlled study

The pharmacokinetics of tobramycin in adolescents or young adults with cystic fibrosis and in age-matched controls were prospectively compared. Patients with CF had a higher tobramycin total body clearance (121.2 +/- 14.2 ml/min/1.73 m2) than did controls (102.2 +/- 18.9 ml/min/1.73 m2, P less than 0.05). This was not associated with a higher glomerular filtration rate (iothalamate total body clearance 147.5 +/- 29.2 ml/min/1.73 m2 in patients vs 142.9 +/- 33.3 ml/min/1.73 m2 in controls) or a lower binding of gentamicin to serum proteins (14.3% +/- 2.6% in patients vs 17.4% +/- 3.8% in controls). Tobramycin renal clearance was not significantly different in the two groups (89.5 +/- 17.9 ml/min/1.73 m2 in patients vs 81.0 +/- 15.8 ml/min/1.73 m2 in controls). In the control group, tobramycin total body and renal clearances were highly correlated with iothalamate total body clearance (r = +0.95 and +0.88, P less than 0.01). In patients with cystic fibrosis, the correlation was not significant (r = +0.56, P greater than 0.05 for total body clearance, and r = 0.32, P greater than 0.1 for renal clearance). There was no significant difference in volume of distribution normalized to body surface area or in half-life of elimination. The higher tobramycin total body clearance without an increase in renal clearance, and the lower correlation with glomerular filtration rate indicate that an extrarenal clearance pathway might play a significant role in the elimination of tobramycin from the serum of patients with cystic fibrosis.     

Persisting glomerular hyperfiltration in short-term diabetic children without microalbuminuria

The renal function in a group of diabetic children (n=29;age;4-17 yr; IDDM duration: 1,5-13 yr) was studied with a 3 year interval. At the first evaluation glomerular filtration rate (GFR) as assessed by inulin clearance was significantly increased compared to control values (167 +/- 32 vs. 124 +/- 18 ml/min/1.73 m2; pl less than 0.01). Eighteen out of 29 children exhibited a glomerular hyperfiltration (GFR greater than 160). Three years later mean GFR was identical (169 +/- 25 ml/min/1.73 m2) and 16 children were hyperfiltrating. Among them, 11 have had a persisting glomerular hyperfiltration over the 3-year period. Renal plasma flow (RPF) was positively correlated to GFR (r=0.7; p less than 0.01) and remained elevated at both evaluations (794 +/- 163 and 812 +/- 157 ml/min/1.73 m2, p greater than 0.01 vs, control values). When the children were separated into 3 groups according to IDDM duration no significant differences were observed in the results for GFR and RPF, Mean urinary albumin excretion was comparable at the 3-year interval, and not significantly different from the control values (5.2 +/- 3.7 and 8.2 +/- 6.6 respectively vs. 8.65 +/- 4 microgram/min). None of the children demonstrated a persistent microalbuminuria. This study reveals a high proportion of diabetic children with a persisting glomerular hyperfiltration, without any other symptom of incipiens nephropathy, If elevated GFR plays an important role in the development of diabetic nephropathy, this study emphasizes the value of regular evaluation of renal function in diabetic children.     

Plasma creatinine, and clearance and urinary excretion of creatinine in children

The 24 hour clearance of endogenous creatinine was compared with that of inulin in 112 children aged between 15 months and 17 years. The children had a variety of kidney disorders with renal function than ranged from normal to terminal renal failure. When the inulin clearance was less than 10 ml/min/1.73 m2 it was on average 75% of the value of the creatinine clearance. Between 10 and 60 ml/min/1.73 m2 the relationship of the inulin clearance to that of creatinine was similar (77%) but above 60 ml/min/1.73 m2 the ratio of the inulin clearance to that of creatinine was 1.05 with a wide scatter. With increasing degrees of renal failure the plasma creatinine increased less in the children under 2 years old than in those over this age so it is poor index of glomerular function in infants. In renal failure the urinary excretion of creatinine in 24 hours was reduced. When the clearance was less than 10 ml/min/1.73 m2, the urinary creatinine excretion for children under the age of 2 was 58% of the normal for the age and for children over 2, it was 86% of the expected mean.     

Short-term effect of low and high protein intake on renal function in children with renal disease

The short-term effect of different levels of protein intake on renal function was investigated in 18 children with moderately (51-85 ml/min/1.73 m2 BSA) or severely (9-50 ml/min/1.73 m2 BSA) reduced glomerular filtration rates (GFR). The GFR and effective renal plasma flow (ERPF), estimated as the clearances of respectively inulin and para-aminohippuric acid during uncontrolled (2-2.5 g/kg bw), low (1.2 g/kg bw for 12 days) and high (3-5 g/kg bw for 24 h) protein intake were determined by a standard clearance method employing continuous infusion and spontaneous voiding. There were no significant differences in GFR or ERPF during uncontrolled and low protein intake. During high protein intake the GFR and ERPF increased significantly in patients with GFRs above 50 ml/min/1.73 m2 BSA and ERPFs above 150 ml/min/1.73 m2 BSA. It is concluded that these findings might indicate a functional reserve capacity in children with only moderately reduced renal function.     

Beta 2 microglobulin. Index of glomerular filtration in children

121 assays for plasma Beta 2 microglobulin (B2M) levels were carried out with an immuno-enzymatic technique in 94 children whose ages ranged from 13 months to 18 years and whose renal functions showed various levels of renal impairment. In the 37 children with normal glomerular filtration rate, plasma B2M level was 1.58 +/- 0.48 mg/l (mean +/- 1 SD) and no significant differences were found according to sex, ages or heights. In the 29 children with glomerular filtration rate (GFR) ranging from 20 to 100 ml/min/1.73 m2, there was a significant correlation between B2M and the inulin clearance, plasma creatinine level and creatinine clearance (p less than 0.001). In 28 patients presenting with terminal renal failure, plasma B2M levels were significantly higher in children undergoing hemodialysis than in those under chronic peritoneal dialysis. These results indicate that B2M levels are as good an index of glomerular filtration rate as serum creatinine whereas its assay uses a long and difficult technique.     

Solitary kidney

The study provides the pediatric practitioner with a tool to determine whether the child with an apparently normal solitary kidney requires an in-depth investigation. Medical records from January 1, 1995 to December 31, 2006 identified 96 children with solitary kidneys and showed 78 with a normal appearing, hypertrophied solitary kidney. Study groups included (1) children 1 to 2 years, (2) girls older than 2 years and boys 2 to 13 years, and (3) boys older than 13 years. Serum creatinine concentrations and estimated glomerular filtration rate were calculated for each group. The mean serum creatinine concentrations in group 1 was 0.4+/-0.1 mg/dL, group 2 was 0.6+/-0.2 mg/dL, and group 3 was 1.1+/-0.2 mg/dL. An estimated glomerular filtration rate 2 SD below the mean suggests further investigation. An estimated glomerular filtration rate 2 SD below the mean was 78 mL/min/1.73 m(2) in group 1, 73 mL/min/1.73 m(2) in group 2, and 70 mL/min/1.73 m(2) in group 3.     

Short-Term Effect of Low and High Protein Intake on Renal Function in Children with Renal Disease

ABSTRACT. The short-term effect of different levels of protein intake on renal function was investigated in 18 children with moderately (51–85 ml/min/1.73 m² BSA) or severely (9–50 ml/min/1.73 m² BSA) reduced glomerular filtration rates (GFR). The GFR and effective renal plasma flow (ERPF), estimated as the clearances of respectively inulin and para-aminohippuric acid during uncontrolled (2-2.5 g/kg bw), low (1.2 g/kg bw for 12 days) and high (3–5 g/kg bw for 24 h) protein intake were determined by a standard clearance method employing continuous infusion and spontaneous voiding. There were no significant differences in GFR or ERPF during uncontrolled and low protein intake. During high protein intake the GFR and ERPF increased significantly in patients with GFRs above 50 ml/min/1.73 m² BSA and ERPFs above 150 ml/min/1.73 m² BSA. It is concluded that these findings might indicate a functional reserve capacity in children with only moderately reduced renal function.     

Serum creatinine level and renal function in children.

OBJECTIVE--To evaluate the accuracy of serum creatinine and height/serum creatinine glomerular filtration rate (Cr-GFR) formula as screening tests for abnormal renal function defined by plasma diethylenetriaminepenta-acetic acid (DTPA) clearance. DESIGN--Patient series. SETTING--The Children's Hospital of Buffalo (NY). PATIENTS--Eighty-seven consecutive patients ranging in age from 2 to 20 years. MEASUREMENTS--The Cr-GFR was calculated by means of the formula GFR (milliliters per minute per 1.73 m2) = kL/serum creatinine (milligrams per deciliter), where L is body length in centimeters and k is a constant dependent on age and sex. Plasma clearance of technetium Tc 99m-labeled DTPA was our reference method for determination of GFR (DTPA-GFR). RESULTS--The Cr-GFR formula identified children with impaired renal function (DTPA clearance, less than 80 mL/min per 1.73 m2) with a sensitivity of 95% and a specificity of 93%. In contrast, the sensitivity and specificity of elevated serum creatinine level for this purpose were 80% and 96%, respectively. Of the children with renal insufficiency (DTPA clearance, 40 to 79 mL/min per 1.73 m2), 91% were correctly identified by the Cr-GFR formula. However, only 65% of these children had elevated serum creatinine levels. Although all children with renal failure (DTPA clearance, less than 40 mL/min per 1.73 m2) had abnormally high serum creatinine levels, the specificity of this test was significantly lower than that of the Cr-GFR formula (75% vs 100%, respectively). CONCLUSIONS--The Cr-GFR formula is superior to serum creatinine level for estimating GFR. This formula provides a simple, reasonably accurate screening test for the presence and severity of impaired renal function.     

Renal function of children receiving long-term parenteral nutrition

Renal function was assessed in 13 children at a mean (+/- SD) age of 9 +/- 4.9 years who had been receiving total parenteral nutrition for 7.9 +/- 4.1 years. All children had normal blood pressure, urinary sediment, and serum creatinine concentrations (58.3 +/- 1.0 mumol/L). Glomerular filtration rate was measured by plasma clearance of diethylenetriaminepentaacetic acid labeled with indium 111. All 13 children had decreased glomerular filtration rate (65.5 +/- 11.9 ml/min per 1.73 m2; range 49.5 to 83.7). Creatinine clearance was 69.1 +/- 10.9 ml/min per 1.73 m2. No tubular damage, as assessed by beta 2-microglobulinuria, was detectable. Renal ultrasonography showed normal architecture with no evidence of nephrocalcinosis in all subjects. The kidney size was normal in seven children; six had reduced (less than -1 SD) size. No relationship was seen between the true glomerular filtration rate and diagnosis, number of episodes of infections, or antibiotics used. The duration of total parenteral nutrition was inversely correlated with the true glomerular filtration rate (r = -0.66, p less than 0.01). The decrease in glomerular filtration rate was not related to the underlying disease or to the nephrotoxic drugs used; the mechanism was not identified. We conclude that long-term total parenteral nutrition is associated with a decrease in glomerular filtration rate.     

Evolution of individual renal function in children with unilateral complex renal duplication

OBJECTIVE: To assess the evolution of individual renal function during the maturation process in terms of single kidney glomerular filtration rate (SKGFR) and split function in children with unilateral complex renal duplication. STUDY DESIGN: We retrospectively reviewed the records of 44 children with unilateral complex duplex kidney. All affected kidneys had a poor or nonfunctioning dysplastic moiety, 28 in the upper pole and 16 in the lower pole. At least 2 radioisotopic examinations, including a 99mTc-mercaptoacetyltriglycine (99mTc-MAG3) renogram and a plasma clearance of 51Cr-ethylenediaminetetraacetic acid (Cr-51 EDTA), were performed in all children, the first one performed at a median age of 3 months (range 2 to 15 months) and the last one at 24 months (range 12 to 120 months). They allowed a precise estimation of split renal function, overall glomerular filtration rate (GFR), and SKGFR. RESULTS: Mean overall kidney GFR increased significantly between the two measurements from 63 +/- 12.7 mL/minute/1.73 m2 to 95 +/- 21 mL/minute/1.73 m2 (P <.0001). SKGFR of the duplex side similarly increased from 26 +/- 7.7 mL/minute/1.73 m2 to 38 +/- 12.6 mL/minute/1.73 m2 (P <.0001). In terms of split function, the affected kidney had a remarkable stable function between the two measurements, 40% +/- 8.6 and 39% +/- 8.3 (P=.94), respectively. However, cases with the lowest initial split function (<30%) had the lowest initial SKGFR and the worst further evolution. CONCLUSION: In children with unilateral complex renal duplication, we found on the affected side a significant increase of SKGFR because of renal maturation, whereas mean split function remained stable during follow-up.     

Renal functional changes in relation to hemodynamic parameters during exercise test in normoalbuminuric insulin-dependent children

AIM: To examine the relationship between filtration fraction and systemic vasculopathy, in normoalbuminuric insulin-dependent diabetic adolescents. METHODS: We calculated filtration fraction from measured glomerular filtration rate and renal plasma flow during a hypotonic saline perfusion test in 30 normotensive adolescent diabetic patients (9-19 years), with a mean duration of diabetes of 7.4 years. Blood pressure and heart rate were measured in basal conditions, during a 24-h ambulatory monitoring and during a dynamic exercise test on a cycle ergometer and peripheral vascular resistance was calculated. RESULTS: Filtration fraction was increased in the diabetic children compared with controls (30+/-6% vs. 22+/-4%, p<0.001), while renal plasma flow was significantly lower (453+/-133 mL/min/1.73 m2 vs. 593+/-155 mL/min/1.73 m2, p<0.001). Peripheral vascular resistance was significantly higher at peak exercise in diabetic children compared to controls (16.3+/-1.3 mmHg/L min m2 vs. 11.4+/-0.5 mmHg/L min m2, p<0.01). CONCLUSION: These results indicate that in young patients with IDDM, without apparent nephropathy or apparent systemic vasculopathy, filtration fraction is increased, suggesting an increased intraglomerular pressure. The associated reduced decrease of peripheral vascular resistance (increased diastolic blood pressure during exercise) suggests that renal functional abnormalities may be partly explained by a systemic vasculopathy, also present in the kidney.     

Effect of low dose dopamine on hemodynamic and renal function in children

The purpose of the study was to investigate the effect of low doses of dopamine in children. Fourteen cases were studied after open heart surgery. Cardiac output and renal parameters were determined under baseline conditions and under continuous infusion of dopamine 2.5 and 5 micrograms/kg/min. During the control period cardiac index was 2.62 +/- 0.19 L/min/m2, renal plasma flow was decreased at 269 +/- 41 mL/min/1.73 m2, GFR was 86.6 +/- 9.2 mL/min/1.73 m2, and filtration fraction was elevated at 37.1 +/- 1.9%. Plasma concentration of aldosterone correlated with the filtration fraction. At 5 micrograms/kg/min dopamine increased significantly cardiac output, renal plasma flow, and to a lesser extent GFR, thus decreasing the filtration fraction. At 2.5 micrograms/kg/min dopamine, increased renal plasma flow only in patients older than 5 y and had no effect on the other parameters. The increase of cardiac output in response to dopamine was abolished by propranolol pretreatment. By contrast, the hemodynamic renal response to dopamine was not altered by beta-blockade. These results indicate that 5 micrograms/kg/min of dopamine could prevent renal failure after open heart surgery in children by increasing renal blood flow and attenuating renal compensatory mechanisms.     

Renal function outcome in pediatric liver transplant recipients

The orthotopic liver transplantation (OLT) allows survival of children followed for severe hepatic injury, provided that the immunosuppressive treatment is prolonged. The nephrotoxicity of cyclosporine predicts the long-term outcome of the adult patients receiving a liver transplant. The aim of this study was to determine the long-term outcome of renal function in children receiving OLT. This study included 12 children, with a median for age of 7.1 yr (2-15 yr) at the time of OLT. The duration of follow-up was at least 4 yr, being 7 yr in 10 patients and more than 10 yr in seven. Renal function was evaluated with the serum level of creatinine, calculated glomerular filtration rate (cGFR), and measurement of glomerular filtration rate using chrome 51 ethylenediaminetetraacetate ((51)Cr EDTA) clearance performed at least once during follow-up. The doses and the serum concentrations (C(0)) of cyclosporine were reported at each study time. The cGFR decreased significantly 2 yr after the OLT [median (range): 106 mL/min/1.73 m(2) (71-150) at the time of OLT vs. 85 mL/min/1.73 m(2) (57-128) 2 yr after the OLT, p = 0.03], and decreased again between 7 and 10 yr after OLT [median (range): 99 mL/min/1.73 m(2) (76-125) 7 yr after OLT vs. 81 mL/min/1.73 m(2) (66-140) 10 yr after OLT, p = 0.04]. Six patients developed chronic renal failure (cGFR from 57 to 80 mL/min/1.73 m(2)) 2 yr after OLT associated with high doses of cyclosporine [median (range): 8.8 mg/kg/day (3.5-13)]. The cGFR overestimated renal function by 16% compared with the isotopic measurement of GFR (p = 0.03). Using the (51)Cr EDTA measurement, six of seven patients followed up more than 10 yr after OLT presented mild (n = 3) or moderate (n = 3) chronic renal failure. In our study, the majority of OLT recipients developed a chronic renal failure 10 yr after transplantation. Cyclosporine seems to be the most important factor responsible for the impairment of renal function. The use of the mycophenolate mofetil, a new immunosuppressive agent, allowing a reduction in the dose of cyclosporine, could minimize renal dysfunction. While awaiting the results of a prospective long-term study, close drug monitoring is advised.     

Surgery of congenital heart defects in deep hypothermic cardiovascular arrest: postoperative renal function

We investigated early postoperative renal function in 55 consecutive infants who underwent cardiac surgery in deep hypothermic circulatory arrest (DHCA). In 15 of these patients detailed studies of glomerular and tubular function of the kidneys were performed. Mean time of circulatory arrest at 20 degrees Celsius rectal temperature was 53 +/- 15 minutes. Acute renal failure was seen in four patients due to cardiogenic shock from which they died on the second and third postoperative day. Urine flow in the surviving 51 infants ranged from 120 to 150 ml/h/1.73 m2. The preoperative creatinine clearance was 50 +/- 23 ml/min/1.73 m2. Postoperatively, creatinine clearance was slightly decreased (42 +/- 16 ml/min/1.73 m2), but had completely recovered after 7 days. The renal transport of phosphate, glucose and uric acid remained unchanged. There was a marked increase in urinary excretion of protein, albumin, alpha-1-microglobin and N-acetyl-glucosaminidase which peaked 7 hours after the operation and then normalized. If sufficient surgical hemodynamics are provided postoperatively, there is only slight impairment of glomerular and tubular function, which demonstrates that DHCA has no negative effect on renal function.     

Glomerular filtration rate in children following renal transplantation

Most studies evaluating renal function post-renal transplantation in children have used serum creatinine (S(Cr)) or estimates of its clearance (C(SCH)). When renal function is impaired both S(Cr) and the C(SCH) overestimate glomerular filtration rate (GFR), especially during cyclosporine therapy. This study measured GFR in 64 children (age range: 4-19 years) with stable renal function who received renal allografts at the Childrens Medical Center of Dallas, 31 from live related donors (LRD) and 33 from cadaveric donors (CAD). 125I-iothalamate clearance (C(IO)) was used as the reference standard for measuring GFR. Data from 100 C(IO) studies, were analyzed and results reported as mean +/- S.E.M. C(IO) performed during the first year after renal transplantation in 23 children who received allografts from LRD was 72.4+/-5.5 ml/min per 1.73 m2 compared to 50.4+/-7.4 ml/min per 1.73 m2 in 18 children who received allografts from CAD (p<0.05). Beyond the first year post-renal transplantation there was no difference in C(IO) between LRD and CAD allografts. When S(Cr) was compared to C(IO), the relationship was nonlinear. C(IO) was also compared to the simultaneous estimation of creatinine clearance by C(SCH). The overestimation of GFR by C(SCH) was inversely proportional to the level of renal function. When renal function was normal or mildly reduced (C(IO) > 50 ml/min per 1.73 m2), C(SCH) closely approximated C(IO). When renal function was moderately to severely curtailed (C(IO) < or = 50 ml/min per 1.73 m2), C(SCH) overestimated C(IO) by 43.6+/-5.6%. The study concludes that in children with renal transplant: 1) C(IO) is higher in allografts from LRD compared to CAD kidneys only in the first 12 months following renal transplantation; 2) S(Cr) is a poor predictor of C(IO); and 3) C(SCH) consistently overestimates GFR children following renal transplantation unless renal function is normal or only mildly decreased.     

Effect on renal function of essential fatty acid supplementation in cystic fibrosis

Changes in renal hemodynamics, sodium homeostasis, renal acidifying capacity, and aldosterone excretion were studied before and after long-term intravenous essential fatty acid supplementation for a period of 3 years in 11 patients with cystic fibrosis. The mean (+/- SD) glomerular filtration rate was high at the start of the study (133 +/- 18 ml/min/1.73 m2 body surface area) and decreased significantly (p less than 0.05) to within normal values after 1 year of essential fatty acid supplementation. The urinary elimination of an oral sodium load initially was very low (3.6 +/- 2.5 mmol/hr/1.73 m2 body surface area vs control subjects' values of 7.9 +/- 2.0; p less than 0.001) and increased during treatment but was not normalized (p less than 0.05 vs control subjects' values). Free water clearance and distal tubular sodium delivery, which were significantly decreased before treatment (p less than 0.01 and p less than 0.001 vs control subjects' values, respectively) did not increase significantly. The mean urinary aldosterone excretion did not significantly differ from that in control subjects before and after treatment. The acidifying capacity was disturbed, indicating a low renal bicarbonate threshold, and was changed during treatment in only 2 of 10 patients. These data indicate that essential fatty acid deficiency may contribute to the renal disturbances in cystic fibrosis.     

Nonoliguric hyperkalemia in the premature infant weighing less than 1000 grams

Eighteen very low birth weight premature infants born before 28 weeks gestation and weighing less than 1000 gm were evaluated prospectively for disturbances in serum electrolyte concentrations and for renal glomerular and tubular functions. Clinically symptomatic hyperkalemia resulting in significant electrocardiographic dysrhythmias developed in eight of these infants; 10 babies remained normokalemic. Peak serum potassium concentration ranged from 6.9 to 9.2 mEq/L in the hyperkalemic group; all potassium values in the normokalemic group were less than 6.6 mEq/L. Indices of renal glomerular function and urine output were similar in both groups; no infant had oliguria. Serum creatinine concentrations were the same in both groups (1.04 +/- 0.16 SD mg/dl in normokalemic vs 1.19 +/- 0.24 mg/dl in hyperkalemic infants, beta less than 0.2 at alpha = 0.05), and glomerular filtration rates did not differ significantly (6.29 +/- 1.78 ml/min/1.73 m2 in normokalemic vs 5.70 +/- 1.94 ml/min/1.73 m2 in hyperkalemic infants, beta less than 0.2 at alpha = 0.05). In contrast, indicators of tubular function revealed a significantly larger fractional excretion of sodium in hyperkalemic infants: 13.9 +/- 5.4% versus 5.6 +/- 0.9% in normokalemic control subjects (p less than 0.001). Hyperkalemic infants also had a tendency toward lower urine concentrations of potassium, although there was no significant difference in their net potassium excretion in comparison with that in the normokalemic group. We speculate that hyperkalemia in the tiny baby is in part the result of immature distal tubule function with a compromise in ability to regulate potassium balance.     

Clinical limitations of the estimation of glomerular filtration rate from height/plasma creatinine ratio: a comparison with simultaneous 51Cr edetic acid slope clearance.

A retrospective comparison of single determinations of glomerular filtration rate measured by 51chromium-edetic acid slope clearance (CEDTA) and height/plasma creatinine ratio (Ht/PC) was undertaken in 199 children aged between 3 and 16 years. Analysis of the data indicated that only if Ht/PC less than or equal to 1.2 cm/mumol per 1 was the relationship between Ht/PC and CEDTA linear. Over this range where renal function is significantly impaired the confidence limits for individual prediction of glomerular filtration rate were so wide that a definitive measurement of renal function would be necessary in clinical practice. Where Ht/PC greater than or equal to 1.2 the relationship was non-linear and the predictive confidence limits very wide. To apply the technique as a screening test for normal renal function (CEDTA greater than or equal to 80 ml/min per 1.73 m2) the Ht/PC would need to exceed 2.16. In our study this would have detected 57 out of 131 patients who had normal glomerular filtration rates and erroneously included 2 out of 68 with subnormal renal function.     

Tubular and glomerular function in children after renal transplantation

Glomerular and tubular function of transplanted kidneys were assessed in 46 children aged 15.7 +/- 4.6 yr, 4.2 +/- 2.8 yr after renal transplantation. There were 34 cadaveric, and 12 living-related donors. Twelve patients (26%) had acute episodes (acute tubular necrosis, rejection, or urinary tract infection) during follow-up. All patients were on triple immunosuppression. The mean serum creatinine was 1.5 +/- 0.6 mg/dL. Creatinine clearance (Ccreat) calculated from a 24-h urine collection was 48.0 +/- 19.7 mL/min/1.73 m(2), and that estimated from the Schwartz formula, 61.0 +/- 22.5 mL/min/1.73 m(2). A positive correlation was found between the calculated and estimated clearances. Mean urine concentrating ability was 487 +/- 184 mOsmol/kg, with a value lower than 400 mOsmol/kg in 35% of patients. There was a positive correlation between urine osmolality and estimated Ccreat. Metabolic acidosis (bicarbonate <22 mmol/L) was found in 41% of patients, with relatively alkaline urine and high chloride level. Fractional excretion (FE) of sodium was above 1% in 68% of patients (mean 1.66 +/- 1.06%), and FE(Mg) was above 3% (mean 10.9 +/- 5.2%) in 93% of patients. Tubular reabsorption of phosphate (TP)/glomerular filtration rate (GFR) was 3.2 +/- 0.8 mg/dL glomerular filtrate (GF). FE(K), FE(UA), and Ca/creatinine in urine were normal. There were no functional group differences between the cadaveric and living-related kidneys. Significant group differences were found in those with acute episodes and those with a normal course. Estimated Ccreat was 54 +/- 20 vs. 67 +/- 20 mL/min/1.73 m(2) in the acute episodes and the normal course groups, respectively. Also, the FE(NA), FE(UA), and FE(Mg) were higher in the acute episodes group -2.3 +/- 1.6, 10.6 +/- 4.4, and 14.8 +/- 6.5%, respectively, compared with the normal course group -1.4 +/- 0.6, 8.2 +/- 2.8, and 9.6 +/- 4.0%, respectively. There were no between-group differences in plasma bicarbonate, FE(K), TP/GFR, and urine osmolality. We believe that most, if not all tubular dysfunctions in the transplanted kidney are secondary to renal failure and interstitial damage from acute episodes and nephrotoxic drugs. These dysfunctions are similar to those in chronic renal failure, where interstitial fibrosis plays a role in kidney function deterioration.     

Effect of metoclopramide therapy on arginine vasopressin excretion and renal water handling in premature infants

The role of endogenous dopamine (DA) in regulating arginine vasopressin (AVP) release and renal water excretion was studied in 10 premature infants with a mean birth weight of 1,341 g (range 1,150-1,660 g) and a mean gestational age of 30.2 weeks (28-33 weeks), who were given metoclopramide (MTC), a specific DA antagonist. It was demonstrated that in response to MTC urine flow rate increased significantly from a basal value of 0.90 +/- 0.07 to 1.27 +/- 0.09 ml/min/1.73 m2 (mean +/- SE; p less than 0.01), urinary sodium excretion from 6.10 +/- 1.47 to 11.7 +/- 2.24 microEq/min/1.73 m2 (p less than 0.025) and osmolar clearance from 0.38 +/- 0.044 to 0.600 +/- 0.075 ml/min/1.73 m2 (p less than 0.01). MTC administration did not cause any alterations in free water clearance, whereas urinary AVP excretion fell significantly from 49.38 +/- 10.13 to 32.66 +/- 6.53 ng/min/1.73 m2 (p less than 0.05) after MTC. It is concluded that, contrary to adults, in low birth weight premature infants endogenous DA is enhancing rather than inhibiting AVP release and the MTC-induced water diuresis is independent of the fall of AVP since free water clearance remained unaltered after MTC.