Combined double lung-liver transplantation for cystic fibrosis without cardio-pulmonary by-pass.

Sequential bilateral single lung-liver transplantation (SBSL-LTx) is a therapeutic option for patients with end stage lung and liver disease (ESLLD) due to cystic fibrosis (CF). A few cases have been reported, all of them were performed with the use of cardio-pulmonary by-pass (CPB). We performed SBSL-LTx in three young men affected by CF. All the recipients had respiratory failure and portal hypertension with hypersplenism. Along with lung transplants, two patients received a whole liver graft and one an extended right graft from an in situ split liver. During transplantation neither CPB nor veno-venous by-pass (VVB) were employed. Immunosuppression was based on basiliximab, tacrolimus, steroids and azathioprine. The three recipients are alive with a median follow-up of 670 days (range 244-1,533). Combined SBSL-LTx is a complex but effective procedure for the treatment of ESLLD due to CF, not necessarily requiring the use of CPB or VVB.

Orthotopic liver transplantation for Byler's disease.

In this study we analyzed the features of 12 patients who underwent liver transplantation for progressive familial intrahepatic cholestasis (Byler's disease [BD]) in view of the technical features of the OLTx, incidence and type of complications, need for retransplantation, as well as patient and graft survivals. BD was the indication in 12 patients of median age 1.32 years and median weight 10 kg. Median follow-up was 670 days. Major surgical complications requiring reintervention occurred in three patients. No thrombosis of the hepatic artery was observed. Infections with positive blood cultures were diagnosed in four patients. One patient had a biliary anastomotic stenosis successfully treated by percutaneous techniques. Four patients had episodes of acute rejection treated with steroids. Two patients were retransplanted, both of whom died in the early postoperative period due to hepatic vein thrombosis and venoenteric fistula. The actuarial patient and graft survival was 83% at 1 year and 83% at 5 years. Split-liver grafts represent an excellent organ supply for these patients, achieving good results with no mortality on the waiting list.

Delayed intestinal visualization at hepatobiliary scintigraphy is associated with response to long-term treatment with ursodeoxycholic acid in patients with cystic fibrosis-associated liver disease.

BACKGROUND/AIMS: Abnormalities of biliary drainage have been documented at hepatobiliary scintigraphy in many but not all patients studied with cystic fibrosis-associated liver disease. Ursodeoxycholic acid was shown to be beneficial in this disease, mainly by improving biliary secretion. Therefore, patients with impaired biliary drainage are expected to obtain the greatest benefit from this treatment. METHODS: We evaluated the effects of long-term treatment with ursodeoxycholic acid in 36 patients with cystic fibrosis-associated liver disease, and compared the response in patients presenting a normal (n=18) or delayed time of intestinal visualization (n=18) at baseline hepatobiliary scintigraphy. RESULTS: The mean treatment duration was 58+/-26 (S.D.) months and 63+/-29 months in the groups with normal or delayed time of intestinal visualization, respectively. The time of intestinal visualization decreased (57+/-23%, p<0.001) from baseline in patients with initially abnormal values and became normal in four (22%). Treatment failure, i.e. lack of sustained normalization of serum liver enzymes or the occurrence of a clinically relevant adverse event, was more frequently observed in patients with a normal time of intestinal visualization at baseline (OR, 5.50; 95% CI, 1.32-22.7). When only clinically relevant adverse events were considered, they occurred in six of the latter patients (liver transplantation in one case, development of ultrasographic or endoscopic signs of portal hypertension in six cases), but in only one patient (development of portal hypertension) in the group with delayed time of intestinal visualization (OR, 10.82; 95% CI, 1.17-100.4). CONCLUSIONS: Delayed intestinal visualization at hepatobiliary scintigraphy in patients with cystic fibrosis-associated liver disease seems to predict a better response to ursodeoxycholic acid.

Adequate clinical control of congenital nephrotic syndrome by enalapril.

The combination of captopril and indomethacin has been shown to control nephrotic proteinuria in an infant with congenital nephrotic syndrome of the Finnish type. We report the satisfactory control of congenital nephrotic syndrome by enalapril, maintaining normal serum albumin levels without albumin infusions. The haplotype data of our patient were consistent with the diagnosis of a Finnish-type nephrotic syndrome. After 21 months, during which daily infusions of albumin allowed partial control of the symptoms, captopril treatment was started. No adverse effects were noted. Serum creatinine levels remained normal. Within 8 weeks, albumin infusions were completely stopped. After 1 month the treatment was changed to a single dose of enalapril (0.8 mg/kg per day). During the next 15 months, the serum protein concentration was maintained around 6.5-7 g/dl, although proteinuria persisted (0.3-0.5 g/day). Weight and length gain are now satisfactory. We conclude that enalapril may be safely used in infants with severe forms of congenital nephrotic syndrome and might allow the avoidance of aggressive treatments for prolonged periods.

Shortcomings in predicting postnatal renal function using prenatal urine biochemistry in fetuses with congenital hydronephrosis.

Ten fetuses with hydronephrosis underwent one to seven urine sampling procedures at 23 to 36 weeks' gestation to evaluate renal function. Postnatally, the infants' renal function was assessed by a combination of serum creatinine measurement, ultrasonography and renal scintigraphy. Six infants had pyelo-ureteric junction obstruction, two had megabladder with megaureter, and two had vesico-ureteric reflux. All infants had normal serum creatinine levels at the time of postnatal follow-up, but five of the seven with unilateral involvement had moderate or severe renal damage. Abnormal urinary electrolyte concentrations were found antenatally in only two of them. For the three infants with bilateral hydronephrosis, postnatal evaluation showed moderately or severely damaged kidneys despite prenatal evidence of normal biochemical indexes. Fetal urine electrolyte measurement may be accurate in the diagnosis of renal dysplasia, but its sensitivity is poor in predicting moderate renal dysfunction.

Acute pyelonephritis as a cause of hyponatremia/hyperkalemia in young infants with urinary tract malformations.

Obstructive uropathy causes tubular resistance to aldosterone and severe metabolic imbalance may be precipitated by an episode of pyelonephritis. In the last 3 years we investigated 52 episodes of pyelonephritis (positive urine culture, elevated C reactive protein, fever, elevated neutrophil count) in 50 children between 15 days and 15 months of age. Ultrasonography voiding cystography and renal scintiscan were performed in all cases and i.v. urography in some. A salt-losing syndrome with hyponatremia and hyperkalemia (Na < 125 meq/liter; K > 6.3 meq/liter) was observed in 17 infants < 3 months, accompanied by plasma aldosterone concentration of 5000 to 23,000 pg/ml (normal value, < 1000 pg/ml). All these children had a severe urinary tract (UT) malformation (ureteropelvic junction stenosis in 7 cases, vesicoureteral reflux in 7, posterior urethral valves in 2, double system in 1). Thirteen infants < 3 months, 7 with no urinary tract malformations, did not have electrolyte imbalance. Pyelonephritis was diagnosed in 20 other patients ages 4 to 15 months, including 16 with severe UT malformations; 4 had normal UTs. We conclude that a salt-losing syndrome with tubular resistance to aldosterone can occur during pyelonephritis in young infants with congenital UT malformation, that the risk diminishes considerably or disappears after 3 months of age and that in the absence of UT malformation pyelonephritis does not cause acute sodium loss of clinical relevance.

Genetic models of arterial hypertension--role of tubular ion transport.

The description of pathogenetic mechanisms underlying different genetic models of essential hypertension is a useful way of illustrating the logical sequence needed to dissect a complex phenotypic condition such as hypertension. The abnormalities in renal function observed in spontaneously hypertensive rats of the Okamoto strain and Milan strain will be emphasized. The description may proceed "downward" from alterations that affect the whole body function to cellular and subcellular levels. However, the identification in the Milan strain rats of a point mutation in the gene coding for adducin, a skeletal protein able to modulate transepithelial sodium transport, provides the opportunity to reconstruct, in an "upward" direction, the sequence of events leading from the single point mutation to the final complex phenotype of essential hypertension.

Severe nephropathy in three adolescents with cystic fibrosis.

Renal involvement has rarely been reported in patients with cystic fibrosis. We describe severe nephropathy with a rapidly fatal outcome in three adolescents with cystic fibrosis, and evaluate the important repercussions that the nephrotic syndrome had on the precarious clinical situation of these patients.

Increased renal tubular Na-K-ATPase activity in Milan hypertensive rats in the prehypertensive period.

Milan hypertensive (MSH) rats develop hypertension around the 3rd-4th week of life and exhibit increased Na-pump activity in adulthood. The present study was performed to evaluate whether or not hypertension is preceded by an increase in Na-K-ATPase activity. Total and ouabain-sensitive ATPase activities were studied in single microdissected medullary thick ascending limb of Henle (mTAL) tubules from MHS, Milan normotensive (MNS) and Sprague-Dawley (SD) rats at 22-24, 26-28 and 45-60 days of age. Data are given as mean +/- SEM. Total and Na-K-ATPase activity exhibited a developmental pattern in MHS, MNS and SD rats. At 22-24 days no difference was seen between MHS and MNS animals. At 26-28 days MHS had a higher total and Na-K-ATPase activity than MNS (3031 + 171 vs 2471 + 178 pmol phosphate/mm tubule per hour, P less than 0.05; 2289 + 205 vs 1653 + 151, n = 10, P less than 0.05). At this age there was still no difference in mean arterial blood pressure (88 + 4 vs 86 + 3 mm Hg, n = 15). Adult MHS rats had higher blood pressure (140 + 9 vs 112 + 8 mm Hg, P less than 0.001) and higher total (3544 + 136 vs 2718 + 215 pmol phosphate/mm tubule per hour, n = 10, P less than 0.01) and Na-K-ATPase activity (2670 + 99 vs 1942 + 217 pmol phosphate/mm tubule per hour, n = 10, P less than 0.05) than adult MNS rats.(ABSTRACT TRUNCATED AT 250 WORDS)

Na,K-ATPase activity in renal tubule cells from Milan hypertensive rats.

Several abnormalities of cation transport have been described in the Milan hypertensive rats (MHS). In this study we examined Na,K-ATPase activity in proximal convoluted tubules (PCT) cells and medullary thick ascending limb of Henle cells (TAL) from MHS and from the Milan normotensive rats (MNS). Na,K-ATPase activity was determined as 32P-ATP hydrolysis in single tubule segments. Na,K-ATPase activity (pmol Pi/mm t/h) was significantly higher in MHS than MNS both in PCT (903 +/- 227 n = 8 v 506 +/- 285 n = 12) and TAL (4324 +/- 800 n = 5 v 3063 +/- 625 n = 5). Na,K-ATPase dependent respiration was determined in PCT cell from MNS and MHS. Under basal condition Na,K-ATPase dependent respiration (mumol O2/mg protein/h) was higher in MHS than in MNS (24.2 +/- 1.8 n = 5 v 16.1 +/- 0.4 n = 5). When the cells were Na loaded by amphotericin Na,K-ATPase dependent respiration increased significantly more in MHS than MNS (38.4 +/- 1.6 v 26.8 +/- 2.2 n = 4). Thus, Na,K-ATPase activity is higher in renal tubule cells both at normal intracellular Na and after the cells have been Na loaded. The results indicate that regulation of Na homeostasis in renal tubule cell is different in MHS and MNS.