Impact of hepatitis on renal transplantation.

In order to delineate the incidence, etiology, and impact of liver disease in renal transplant patients, we reviewed 405 consecutive transplants performed between 1970 and 1980. Hepatic dysfunction of at least 2 weeks' duration was diagnosed in 42 patients (10.4%). Of 28 patients acquiring hepatitis in the first post-transplant year, 26 (92.8%) developed chronic hepatitis; of 14 acquiring hepatitis after the first year, 9 (64.2%) developed chronic hepatitis. Of the 42 patients, 19 (45.2%) died, as compared with 16% of the nonhepatitis patients (P less than 0.001). Only one of these patients died of liver failure, with 15 of the 19 (78.9%) dying of extrahepatic infection. In addition, 12 of the 23 survivors (52.1%) suffered life-threatening infections from which they recovered, as compared with 20% of the nonhepatitis patients (P less than 0.01). Conversely, graft survival was significantly increased among the hepatitis patients (73% 1-year cadaveric allograft survival as compared with 50% for the nonhepatitis patients (P less than 0.01)). The etiology of the liver disease was identified in the minority of patients: 5 (11.9%) with hepatitis B, with none occurring since 1973; 10 (23.8%) with evidence of cytomegalovirus infection; and 1 (2.3%) with azathioprine toxicity. We conclude that the major cause of liver disease in renal transplant patients is non-A, non-B hepatitis, and furthermore, that this disease has a marked immunosuppressing effect resulting in increased allograft survival and a marked increase of life-threatening extrahepatic infection.

Treatment of acute renal allograft rejection with OKT3 monoclonal antibody.

Eight cadaver donor renal allograft recipients, who had received azathioprine and prednisone from the day of transplantation, were treated with OKT3 monoclonal antibody (reactive with all mature peripheral blood T cells) at the time of diagnosis of acute rejection. In all cases, loss of essentially all detectable peripheral blood OKT3-reactive cells was noted within minutes after the initial 1- to 5-mg i.v. infusion. Chills and fever invariably occurred following the first or second infusion of monoclonal antibody, but were not noted during the subsequent, 10- to 20-day course of therapy, suggesting rapid cell lysis as the etiology of this toxicity. The established rejection episode was reversed in all cases within 2 to 7 days without addition of any therapy other than OKT3 antibody and despite continued lowering of the steroid dosages. During the subsequent 3- to 12-month follow-up period, further rejection episodes occurred in five of these patients, two of these were irreversible with conventional therapy so that six of the eight allografts continue with excellent renal function. These preliminary observations suggest that homogeneity, limited dosage requirements, and ease of in vitro monitoring of dosage effects should markedly simplify the use of monoclonal antibody to T cell populations in human allograft recipients. This second generation of antilymphocyte preparations offers the potential for not only increased effectiveness but also the possibility of manipulating specific T cell subsets.

Increased nuclear factor-kappaB and angiotensinogen gene expression in posttransplant recurrent focal segmental glomerulosclerosis.

In an attempt to identify potential markers of steroid-resistance in focal segmental glomerulosclerosis (FSGS) we evaluated intra-graft gene expression of IkappaBalpha, nuclear factor-kappaB (NF-kappaB), and angiotensinogen in 60 biopsies from 27 pediatric renal transplant recipients. Intra-graft NF-kappaB expression was significantly elevated in recurrent FSGS (R-FSGS) (218.3 + 55.6 ag/fg versus NON-FSGS 121.1 + 19.9, P=0.04) but not in acute rejection. NF-kappaB:IkappaBalpha ratios were higher in cadaveric donor versus living related donor recipients (15.7 + 2.8 vs. 8.8 + 1.3, respectively, P=0.015), and in African-American versus Caucasian recipients (15.6 + 2.9 vs. 9.1 + 1.3, respectively, P=0.03). Intra-graft angiotensinogen gene expression was significantly elevated in R-FSGS (30.5 + 8.8 ag/fg R-FSGS vs. 16.0 + 4.7 NON-FSGS, P=0.009). We conclude that increased NF-kappaB and angiotensinogen gene expression are associated with R-FSGS. Increased NF-kappaB:IkappaBalpha ratios are associated with cadaveric donor recipients and African-American race.

Varicella in pediatric renal transplant recipients.

As of November 1991, 8 of 83 children who had received renal transplants at Massachusetts General Hospital since January 1979 required admission for primary varicella. All 8 had cutaneous manifestations of disease, and 4 had evidence of visceral disease. Three of these 8 children received varicella zoster immune globulin (VZIG) after exposure to varicella; in the remaining children, exposure was not revealed until symptoms were present. All 8 children were treated with high-dose intravenous acyclovir. Two children died of complications of varicella infection, including 1 child who received VZIG on the day of exposure to varicella. Neither VZIG prophylaxis nor treatment with intravenous acyclovir offers complete protection against severe varicella infection to immunosuppressed children who have received organ transplants. A high priority should be given to the evaluation of alternative treatments, such as vaccination to the varicella virus, which could be administered to susceptible transplant candidates, preferably prior to transplantation.

Studies on the pathophysiology of encephalopathy in Reye's syndrome; Hyperammonemia in Reye's syndrome.

The initial acid-base status of eight survivors of Reye's syndrome was characterized by acute respiratory alkalosis (Pco2=32 mm Hg; Hco3-=22.0 mEq/liter) while that of eight children who died was associated with metabolic acidosis as well (HCO3-=10.0 mEg/liter). Arterial-internal jugular venous ammonia concentration differences on day 1 (299 mg/100 ml) and day 2 (90 mg/100 ml) reflected cerebral uptake of ammonia while those on days 3 and 4 (-43 and -55 mg/100 ml) demonstrated cerebral release. Arterial blood hyperammonemia can be detoxified safely in the brain as long as the levels do not exceed approximately 300mug/100 ml. Beyond that level lactic acidosis is observed, particularly in cerebral venous drainage. Arterial blood hyperammonemia was also related to the extent of alveolar hyperventilation. These findings are very similar to those seen in experimental hyperammonemia and support the concept that neurotoxicity in children with Reye's syndrome is at least partly due to impaired oxidative metabolism secondary to hyperammonemia.

Genital abnormalities in females with Bardet-Biedl syndrome.

The major manifestations of the Bardet-Biedl syndrome are digital anomalies, tapetoretinal degeneration, obesity, renal abnormalities, and hypogenitalism (described mainly in males). We report on 2 girls with Bardet-Biedl syndrome who also had vaginal atresia. A similar association in females with Bardet-Biedl syndrome was suggested in published reports of 11 affected individuals who had structural genital abnormalities, (some of which were missed in childhood), including persistent urogenital sinus, ectopic urethra, hypoplasia of the uterus, ovaries and fallopian tubes, uterus duplex, and septate vagina. The association of atresia of the vagina and other malformations of female genital structures in individuals with Bardet-Biedl syndrome has often been missed in childhood and should be looked for more systematically.

Second renal transplantations. Ethical issues clarified by outcome; outcome enhanced by a reliable crossmatch.

OBJECTIVE: To determine whether the appropriate use of scarce donor resources has been accomplished by renal retransplantation by reviewing the initial and long-term outcomes of second-renal transplant recipients at the Massachusetts General Hospital, Boston. PATIENTS AND RESULTS: With a mean follow-up of nearly 5 years following transplantation, 54 (68%) of 80 second-transplant recipients had functioning allografts (allograft failure was defined by patient death or a return to dialysis). Rejection was the most common cause of failure (14 [54%] of 26 patients). The 1-, 3-, and 5-year actuarial allograft survival rates were 86%, 78%, and 69%, respectively, which were not significantly different from the survival rates of primary allografts at this center. These results support the continued approach of providing both cadaver-donor and living-donor renal allografts for recipients whose primary renal allograft has failed. The antiglobulin crossmatch may have contributed to the successful outcome by accurately determining compatibility and by averting early rejection failures. CONCLUSIONS: Health care policy reviewers should clearly distinguish the prospects for successful second renal transplants from the outcomes of extrarenal retransplantation. Moreover, because excellent second-renal allograft survival is attainable and comparable to primary-renal allograft survival and because the costs are comparable, restricting suitable patients to subsequent lifelong dialysis becomes unethical.

Complications of pediatric percutaneous renal procedures: incidence and observations.

Successful definitive (complete) percutaneous renal procedures in the pediatric age group were performed in 97 per cent of antegrade pyelograms, in 94 per cent of ureteral perfusions (Whitaker test), in 98 per cent of nephrostomies, and 100 per cent of both retroperitoneal fluid drainages and renal aspiration biopsies. Significant complications, or those necessitating specific treatment or prolonged hospitalization, were 1.1 per cent. 0.7 per cent, 15.2 per cent, 0 per cent, and 0 per cent, respectively, for the above procedures. Not surprisingly, certain operators are more adept than others at successfully performing procedures and at avoiding some but not all complications (see Tables 2 and 3). Proper training, experience, and adherence to basic principles are important. However, there were no deaths, no kidneys lost, and no transfusions or operations required as a result of any complication from the pediatric percutaneous renal procedures; correction of any existing blood coagulation disorder is necessary prior to their performance to avoid potentially fatal hemorrhage.

Surgically correctable hypertension of renal origin in childhood.

Since 1960, 22 children were treated for surgically correctable hypertension or renal origin. The series included two children with tumors, two with hydronephrosis from ureteropelvic junction obstruction, nine in whom one kidney was atrophic, and nine with renal artery narrowing from fibromuscular dysplasia (with bilateral involvement in two). Hypertension was cured in the cases with tumors and ureteropelvic junction obstruction. It was also cured in four of the nine patients with an atrophic kidney and in five of the nine with a narrow renal artery. In those not cured hypertension was more easily controlled by medication. One patient died from brain hypoxia during surgery. About 10 percent of the children investigated for hypertension at the Massachusetts General Hospital proved to have a surgically correctable cause of renal origin.

Infantile polycystic disease of the liver and kidneys.

Kidney and liver tissue from eleven patients with recessively inherited infantile polycystic disease (IPCD) were examined to document the extent of renal tubular cyst formation and hepatic fibrosis, to assess survival, and to examine the usefulness of current classifications. Four infants with 90% or more cystic renal change did not survive beyond twenty days. In contrast five of the seven less severely diseased patients with a 20-75% range of cystic change are still alive at six to twenty-one years of age. Liver samples showed hamartomatous bile duct proliferation in all patients studied with the most prominent portal fibrosis in the oldest patient. In both families with two affected siblings, the clinical course and pathological expression of renal disease were dissimilar. Tissue analysis from these cases is consistent with the idea that IPCD has a spectrum of phenotypic expression with prognostic implications from tissue diagnosis in the individual patient, but not necessarily as four genetically determined rigidly defined subgroups. It is concluded that each affected child with IPCD must be evaluated separately.

Increased intraabdominal pressure and anuria in the newborn.

Elevated intraabdominal pressure as a cause of anuria in the critically ill newborn with ascites should be considered after hypovolemia and other causes of intrinsic renal disease or obstruction have been excluded. In the rare patient with ascites who develops anuria, paracentesis should be considered if urine output cannot be established.

Management of children with progressive renal failure.

The strategy of management in childhood renal failure is to integrate available therapeutic modalities with the natural history of the disease in such a manner that linear growth is preserved. Attention to psychosocial growth is necessary for full rehabilitation. Treatment is ordered to provide hope and confidence to family and patient. Conservative medical therapy provides chemical stabilization and prophylaxis against bone disease and growth retardation. Planned progression to replacement of renal function by dialysis or renal transplant is made when growth or control of bone disease is no longer possible, but before complications occur. Therapy is effective; 90% of patients survive 5-10 years with 65% retaining a functioning allograft. Full rehabilitation is attained in 85-90% of post-transplant and 50% of dialysis patients. Technical advances now allow safe dialysis for all age groups. Although growth maintenance remains a major problem, it is possible that earlier metabolic control and transplantation to protect growth in the critical early years, together with improved control of rejection, may allow close approximation to optimal growth potential.

Autosomal recessive polycystic kidney disease: long-term sonographic findings in patients surviving the neonatal period.

OBJECTIVE: We studied the sonographic findings and the changes in renal function seen on long-term follow-up of children who had the initial diagnosis of autosomal recessive polycystic kidney disease made in the neonatal period. MATERIALS AND METHODS: The case records and sonograms of 14 children with biopsy evidence of autosomal recessive polycystic kidney disease were evaluated. Nine children who survived the neonatal period were followed up for a mean of 13 years (range, 5-19 years) after diagnosis and form the basis of this study. Serial changes in renal size, echogenicity, and function were assessed sonographically. The imaging findings were compared with those described in published reports. RESULTS: The sonographic findings showed that five of the nine children had a decrease in renal size, and three had stable renal size over a minimum follow-up period of 5 years. Only one of the nine survivors showed progressive increase in renal size. All had increased cortical echogenicity and large kidneys. Three patients showed a subjective change in renal echogenicity over time. A change in the echogenic pattern to one that resembles autosomal dominant polycystic kidney disease was noted with no evidence of increase in size of the kidneys. None of the surviving children had renal stones or massively enlarged kidneys. The renal function of seven of the nine survivors has remained stable with creatinine clearance nearly normal (> 60 ml/min/1.73 m2), and there was no correlation between renal size and renal function. CONCLUSION: In patients with autosomal recessive polycystic kidney disease who survive the neonatal period, kidney size as seen on sonograms does not continue to increase despite the patients' linear growth and maintained normal renal function. Rather, a decrease in kidney size and change in echogenicity occurs, producing a pattern that is similar to that seen on sonograms of patients with autosomal dominant polycystic kidney disease but without the marked increase in kidney size that occurs in that entity. This changing cystic pattern on follow-up sonograms may be the reason that previous descriptions of the sonographic findings in cases of autosomal recessive polycystic kidney disease have varied and why a decrease in size may not herald deteriorating renal function.

Coexisting nephrolithiasis and cholelithiasis in premature infants.

Though the coexistence of nephrolithiasis and cholelithiasis in premature infants is extremely rare, we report four patients seen in a two year period. All patients weighed less than 1100 grams at birth, developed severe bronchopulmonary dysplasia, and all had Grade III or IV bilateral intraventricular hemorrhages. All four infants received prolonged furosemide therapy lasting at least 28 consecutive days. The renal stones disappeared in all four upon cessation of therapy, while in none have the gallstones disappeared after a mean follow-up period of 13 months. Ultrasound was superior in identifying and monitoring these stones. Their presence resulted in manipulating diuretic therapy which then was shown to limit renal and possibly biliary complications.

Percutaneous ultrasonic lithotripsy of symptomatic renal calculi in children.

Percutaneous ultrasonic lithotripsy of upper urinary tract lithiasis is a well-established procedure in adults. We successfully applied this technique to completely remove symptomatic renal calculi in two children with idiopathic hypercalciuria. The procedure was well tolerated and no complications occurred. Both patients were discharged within 4 days of the lithotripsy. This method is an alternative to surgery for the removal of large or impacted calculi from the upper urinary tracts of pediatric patients.