Graziella Cavanna

Persistent tubular resistance to aldosterone in infants with congenital hydronephrosis corrected neonatally

Renal function of 18 infants who had undergone surgery in the neonatal period because of severe congenital hydronephrosis was followed up for 5 to 36 months (mean +/- SD 21 +/- 10 months). In all cases the diagnosis was made prenatally by sonography and confirmed at birth by intravenous urography. Creatinine clearance developed normally in all the children. Eight had a reduction in maximal urinary concentrating ability after intranasal DDAVP; this defect was transient and resolved after 4 to 5 months in all but one child, in whom it persisted. However, other tubular abnormalities were present. Throughout the observation period, patient serum potassium concentrations were significantly higher than normal, paralleled by a significant increase in plasma aldosterone concentration but with normal excretion fraction of sodium and potassium. There were no disturbances of acid-base balance. These findings may be accounted for by a persistent partial reduced sensitivity of the distal tubule to the action of aldosterone despite normal renal function. This alteration is usually mild, but may constitute a persistent metabolic risk despite successful surgical intervention.

Methodological and clinical aspects of urinary N-acetyl-glucosaminidase in pediatric subjects☆

The enzymatic kinetics of urinary N-acetyl-β-glucosaminidase was studied in healthy newborns and children and in a group of infants with renal diseases. Apparent Km values did not differ in healthy and sick children but were 50% lower in neonates (P < 0.01). Vmax values were higher in patients with renal diseases or on treatment with aminoglycosides, and in neonates. This study confirms that urinary NAG is a useful indicator of a renal injury and suggests that a different isoenzyme is excreted in large amounts early in life. The necessity of diluting urines before assay in order to reduce the inhibition caused by an unidentified dialyzable native substance is discussed and an internal standard method is proposed.

Follow-up study of enzymuria and β2 microglobulinuria during cis-platinum treatment

SummaryTwenty patients with epithelian ovarian cancer treated with DDP (cis-diammine-dichloroplatinum II) 50 mg/m2 were followed for 24 weeks in order to assess the nephrotoxicity of the drug. Ten patients received the total dose in one day with heavy osmotic hydration (Group A), and for the other 10 the dose was subdivided over 3 consecutive days (Group B). The renal tubular toxicity of DDP treatment was evaluated over a total of 120 courses. After the first DDP administration, there was a prompt, reversable and dose-dependent increase in the urinary excretion of β2 microglobulin with no difference between the two groups: Group A from 405 to 990 and Group B from 109 to 585 ng/mg creatinine. An increase always occurred during subsequent courses, but it was significantly lower in Group B after the sixth course, from 125 to 331 ng/mg creatinine. A similar pattern was found for the urinary excretion of N-acetyl-glucosaminidase (NAG), a lysosomal enzyme of tubular origin. The percentage fraction of urinary sodium excretion (FeNa%) increased after each dose of DDP; Group A from 0.82 to 2.30 and Group B from 0.68 to 2.53. This effect was reversible and it occurred to the same extent during the subsequent courses. There was no impairment of the glomerular filtration rate. Thus, enzymuria and β2 microglobulin excretion are a sensitive tool to reveal minor tubular damage. Their use to predict serious renal dysfunction in longitudinal studies, however, seems questionable.

Proximal tubular function and hyperfiltration during amino acid infusion in man

The relations between renal hemodynamics (Inutest, CPAH) and sodium segmental handling (sodium distal delivery, distal reabsorption, and fractional excretion) were studied in 9 healthy adults infused with an isotonic amino acid solution and in 6 subjects infused with 0.9% saline for 3 h at 0.2 ml/min/kg. During all tests maximal water diuresis was induced and maintained to effect analysis of sodium segmental transport. Both types of infusion produced a similar expansion of extracellular volume (weight increase, hematocrit fall, suppressed plasma renin activity and plasma aldosterone). The amino acid infusion increased the glomerular filtration rate (GFR) and renal blood flow without modifying the filtration fraction. With saline no hemodynamic modifications were observed. The expansion with saline depressed proximal and distal sodium reabsorption whereas during amino acid infusion sodium distal delivery was unaltered and the significantly increased sodium fractional excretion was sustained only by depressed distal reabsorption. Therefore, in parallel with the GFR increase, closely dependent on renal vasodilatation, the well-known stimulation of sodium cotransport by amino acids is able to antagonize the effects of expansion on the proximal sodium reabsorption. An explanation of glomerular hyperfiltration based on a primary metabolic stimulation of the proximal tubular function is suggested.

Early Childhood Hyperkalemia: Variety of Pseudohypoaldosteronism

ABSTRACT. Fractional excretion of electrolytes, renal acidification capacity and the renin‐aldosterone system have been studied in 5 non‐azotemic children, 19‐25 months old, with mineralo‐corticoid resistant hyperkalemia, discovered in the first month of life. Although fractional potassium excretion was similar in patients and in a group of control healthy children (13.8± 5.2% vs. 8.7±6.4%) it was inappropriately low in the patients for their higher potassium concentration. Fractional sodium excretion was significantly increased in the patients (1.6±0.3% vs. 0.67±u.4, p<0.02). Normal net acid and ammonium excretion and intact ability to lower urinary pH during acid loading were observed in all patients. Mean values for plasma aldosterone (37.0±9.1 vs. 13.9±11.2 ng/dl), plasma renin activity (12.5±3.9 vs. 8±2.8 ng/ml/h) and plasma aldosterone/plasma potassium ratio (7.11±1.5 vs. 3.08 ±1.7) were higher in the patients than in the control subjects (all p<0.001). These data support the hypothesis that a partial lack of response of the renal tubule to endogenous mineralocorticoids was present in the patients. This type of pseudohypoaldosteronism is less severe than that described for the classic form and for early childhood renal acidosis.

Sodium excretion and hyperfiltration during glucose infusion in man

The relations between renal hemodynamics (Inutest, CPAH) and sodium excretion were studied in 7 nondiabetics in whom a similar expansion was induced (1) with a 3-hour 5% glucose infusion and (2) with a 0.9% saline load. With both infusions the body weight increased, hematocrit fell, and the plasma renin activity was suppressed. During glucose infusion, blood glucose rose from 3.9 mmol/l to a plateau of around 13 mmol/l; glycosuria was absent during the 1st h, then appeared and stabilized during the following 2h. Glucose infusion caused a progressive increase in glomerular filtration rate and in renal blood flow in both absence and presence of glycosuria, without significant changes in sodium excretion despite volume expansion and increase of filtered sodium load. When saline was infused, there was a sustained increase of fractional sodium excretion, and no hemodynamic modifications were observed. We suggest that a primary glucose-induced metabolic stimulation of sodium reabsorption may play a role in the genesis of glucose-induced hyperfiltration.

Renal Function in Cystic Fibrosis

The effect of saline extracellular volume expansion (4 ml/min/10 kg b.w. X 60 min) on renal function has been studied in patients with cystic fibrosis (CF) and in normal age-matched controls. Basal values for glomerular filtration rate (GFR), renal plasma flow (RPF), tubular sodium and chloride (Na, Cl) handling were similar in both groups. Saline expansion resulted in an increase in GFR and RPF in the CF patients: 127 +/- 18 ml/min/1.73 sqm BSA to 166 +/- 5; p less than 0.001, but not in the control group: 112 +/- 10 to 120 +/- 20. These hemodynamic changes were associated with increased proximal tubular reabsorption of NaCl in the CF patients whereas controls had reduced NaCl reabsorption. Renin and aldosterone levels suggested that increased NaCl reabsorption in CF patients was not secondary to chronic extracellular volume contraction or salt loss. These results support the hypothesis that the renal tubule is involved in the generalised electrolyte transport disorder exhibited in other epithelial structures. This study also indicated that the regulation of renal hemodynamics is altered in CF. The relationship between the disorder of proximal tubular salt handling and changes in renal hemodynamics is not known, but the observed changes imply a tubulo-glomerular feedback mechanism.

RENAL FUNCTION IN CYSTIC FIBROSIS |[lpar]|CF|[rpar]|

9 CF patients (15 to 18 years old;Schwachman score 80-90)and 7 control subjects (C) matched for age were investigated for glomerular function (Clin (min 1.73sqm)Na, HCO3- urinary ecretion;Na HCO3- distal delivery (DD:CH2O+CNa;CH2O+CHCO3-)during maximal water diuresis (I)and with isotonic saline infusion (4 ml/kg/min, II).Comparison between groups was performed by the Student t test Results;mean (± SD)These data show that proximal tubular reabsorption of both Na and HCO3 is increased in CF.No difference was found in distal tubular function studied by measuring the urinary excretion of NH4+ and percentage of Na distal reabsorption.

Effect of amino acids and their analogues on renal function

Renal hemodynamics (Cinutest, CPAH) were measured in 5 volunteers (23–28 years of age), before and after each of the following 1-week regimen: a) low protein diet as 50% of usual intake (LPD); b) LPD + 0.6 g/kg of a mixture of essential and non essential amino acids (AAmix); c) LPD + 0.6 g/kg of branched chain amino acids (BCAA); d) LPD + 0.15 g/kg of essential amino and Keto acid supplement (EAKA). LPD induced a decrease in renal plasma flow (RPF) without GFR variation; this finding was annulled when LPD was supplemented either with AAmix or EAKA, suggesting that EAKA used as supplement of LPD in chronic renal disease could counterbalance the low-protein induced reduced glomerular hemodynamic load. BCAA tended to antagonize the LPD renal effects: these data were partially inconsistent with the renal vasoconstriction we previously observed during BCAA infusion in normal man.

RENAL FUNCTION IN INFANTS WITH CONGENITAL HYDRONEPHROSIS OPERATED IN THE FIRST MONTH OF LIFE

In utero diagnosis of hydronephrosis may allow early surgical intervention with possible beneficial effects on the long term renal function. We have prospectively followed 13 of such neonates with grade 3-4 hydronephrosis who had been operated in the first month of life. 10 stenosis of the pyelouretheral junction (5 monolateral), 2 vescicouretheral reflux (1 monolateral), 1 uretral valves. Serum creatinine, electrolytes, maximal urinary concentrating ability after DDAVP, urinary acidification and ammoniogenesis after oral NH4Cl, PRA and serum aldosterone concentration were measured at various intervals. The follow up ranges from 4 to 40 months. Creatinine clearance was normal in all infants at all ages, reduced concentrating ability (Osmu 700) was present in 11/13 infants 9 months but tended to disappear after 2 months. 10/13 infants had mild hyperkalemia (K+5.5-6.5 mEq/1) during the first months. This was accompanied by serum aldosterone concentrations exceeding the normal values for age and suggests a reduced tubular response to aldosterone. A deficient ammoniogenesis was present in 3/13 subjects but all could normally lower U pH below 5.5. UTIs were a minor problem (0.5 episodes/months/infant). These results indicate that mild tubular impairment is present in neonates with congenital hydronephrosis after neonatal surgical correction and tend to ameliorate gradually.