Transjugular intrahepatic portosystemic shunt prior to renal transplantation in a child with autosomal-recessive polycystic kidney disease and portal hypertension: A case report.

Autosomal-recessive polycystic kidney disease (ARPKD) can cause renal failure and portal hypertension in children. Portal hypertension may complicate the course of renal transplantation (Tx). We report the successful outcome of a patient with end-stage renal disease (ESRD) and portal hypertension treated with transjugular intrahepatic portosystemic shunt (TIPS), a minimally invasive endovascular technique of portosystemic shunt, prior to renal Tx.

Neoral pharmacokinetics in Latino and Caucasian pediatric renal transplant recipients.

Interpopulation variability of drug pharmacokinetics (PK) has been described. For example, the systemic clearance of nifedipine is higher in Mexicans than Caucasians. African-Americans have a lower cyclosporine bioavailability than Caucasians. Limited data are available in the Latino population. Under identical conditions, we compared the PK profile of Neoral (cyclosporine for microemulsion) obtained in stable pediatric renal transplant recipients of Latino and Caucasian origin. A slightly lower area under the curve (AUC) when corrected for dose per body surface area or per kilogram of body weight was observed in Caucasians compared with Latinos. This difference was more pronounced in the younger age group (< 12 years) with a higher peak-to-trough ratio. However, the Caucasians required a higher dosage of Neoral than the Latinos to achieve that same AUC. There was no difference between the groups in the time (tmax) to reach maximal concentration (Cmax) of Neoral. A higher apparent clearance of the drug was observed in the Caucasians compared with the Latinos, especially in the younger age group. No differences in pre- and post-dose levels were observed between the two groups. These differences might affect dose adjustment between the two subpopulations.

Hais cuaj txub kaum txub--to speak of all things: a Hmong cross-cultural case study.

Cross-cultural medicine is a field that describes how disparate value and belief systems concerning health and disease affect the delivery of health care. This report describes the conflict between a Hmong immigrant family and the Western medical establishment over the care of their child with end stage renal disease [ESRD]. The health care providers, social service agencies and medical center failed to adequately respond to the needs of the family. The medical staff [nephrologist, nurse coordinator, dietician, social worker, and CPS worker] worked with a transcultural nurse, Hmong community health worker and the family, to design and negotiate a treatment plan that would be acceptable to the family and the health care team. Trust was reestablished between the family and the healthcare providers and the medical outcome for the child improved.

Procalcitonin is a marker of severity of renal lesions in pyelonephritis.

OBJECTIVE: In an attempt to differentiate acute pyelonephritis from lower urinary tract infection (UTI), we measured serum procalcitonin levels, a recently described marker of infection. We compared it with other commonly used inflammatory markers and evaluated its ability to predict renal involvement as assessed by dimercaptosuccinic acid (DMSA) scintigraphy. METHODS: Serum C-reactive protein, leukocyte counts, and procalcitonin levels were measured in 80 children, 1 month to 16 years of age, admitted for suspected pyelonephritis. Renal involvement was assessed by 99mTe-DMSA scintigraphy in the first 5 days after admission. The examination was repeated at least 3 months later if the first result was abnormal. RESULTS: In lower UTI, the mean procalcitonin (PCT) was 0.38 micrograms/L +/- 0.19 compared with 5.37 micrograms/L +/- 1.9 in pyelonephritis. In these two groups, respectively, leukocyte counts were 10939/mm3 +/- 834 and 17429/mm3 +/- 994, and C-reactive protein (CRP) levels were 30.3 mg/L +/- 7.6 and 120.8 mg/L +/- 8.9. When inflammatory markers were correlated to the severity of the renal lesion as ranked by DMSA scintigraphy, we found a highly significant correlation with plasma levels of PCT, but borderline significance with CRP and none with leukocyte counts. Patients without vesicoureteral reflux had a mean PCT of 5.16 micrograms/L +/- 2.33, which was not significantly different from that in patients with reflux who had a mean PCT of 5.76 micrograms/L +/- 3.49. For the prediction of renal lesions at admission, CRP had a sensitivity of 100% and a specificity of 26.1%. The sensitivity and specificity of PCT were 70.3% and 82.6%, respectively. CONCLUSION: We conclude that serum PCT levels were increased significantly in children with febrile UTI when renal parenchymal involvement (assessed by DMSA scintigraphy) was present and allowed for prediction of patients at risk of severe renal lesions.

Effect of plasma from patients with idiopathic nephrotic syndrome on proteoglycan synthesis by human and rat glomerular cells.

In vivo and in vitro findings have shown that plasma of patients with idiopathic nephrotic syndrome (INS) contain factors that increase glomerular permeability to proteins. The effects of these factors on proteoglycan synthesis by glomerular cells are unknown. To investigate the effect of plasma from patients with INS (n = 23) and other glomerulopathies (n = 12) on the amount of proteoglycans synthesized by cultured rat mesangial cells and human glomerular epithelial cells, glomerular cells were cultured for 24 h with plasma from patients or control subjects, and incorporation of Na2(35)SO4 in chondroitin dermatan sulfate and heparan sulfate was assessed using a cationic nylon membrane. The mean ratio of glycosaminoglycan produced by rat mesangial cells when in contact with plasma (5%) from INS patients to the amount produced when in contact with control plasma was 0.70+/-0.06. The mean ratio of heparan sulfate was 0.58+/-0.08. The decrease of heparan sulfate production was present in the cellular and in the extracellular fraction. It was observed when the cells were in contact with plasma from patients in relapse but not when in remission. No decrease of heparan sulfate production was observed with four of the five patients with membranous glomerulonephritis (ratio of 1.27+/-0.03), IgA nephropathy (n = 5, ratio of 1.27+/-0.03), and membranoproliferative glomerulonephritis (n = 2, ratio of 1.39+/-0.34). When human glomerular epithelial cells were exposed to 5% plasma from INS patients in relapse (n = 9), the mean ratio of heparan sulfate was 0.62+/-0.06 in the cellular fraction and 0.72+/-0.08 in the medium. When in contact with plasma from patients in remission, no difference of glycosaminoglycan production was observed. A factor present in plasma from patients with INS during initial episodes or relapses is able to decrease the proteoglycan production of glomerular cells.

Influence of heparin and type-IV collagen on IL-6 synthesis by rat glomerular mesangial cells.

Recent studies have revealed the potential importance of the extracellular matrix (ECM) in the modulation of mesangial cell (MC) function. Interleukin-6 (IL-6) is produced by MCs and was shown to induce MC proliferation, acting as an autocrine growth factor. Heparin is a known inhibitor of MC proliferation. It was shown to modulate ECM synthesis by cultured MCs. The action of heparin on IL-6 synthesis by MCs is presently unknown. We investigated the effect of heparin on IL-6 production when MCs were cultured with or without type-IV collagen, a major constituent of ECM. When MCs were cultured without coating, heparin significantly decreased their IL-6 production; on type-IV collagen, heparin had no significant effect. When tumor necrosis factor alpha (TNF-alpha) was used to stimulate the cells to produce IL-6, heparin was able to decrease the stimulatory effect of TNF-alpha when the cells were cultured on plastic but not when in contact with type-IV collagen. Thus we conclude that heparin has an inhibitory effect on IL-6 secretion by MCs that is prevented by type-IV collagen.

Are younger children at highest risk of renal sequelae after pyelonephritis?

BACKGROUND: The general belief about the relation between risk of renal sequelae after pyelonephritis and age is that infants are at highest risk and children older than 5 years at lower risk. This assumption has led to differences in treatment based on age. The aim of this prospective study was to investigate the occurrence of renal lesions in children aged 0-16 years. METHODS: Between May, 1994, and January, 1996, all children aged 0-16 years who were admitted to our department with a diagnosis of probable pyelonephritis and a positive urine culture were included in this prospective study. All patients received antibiotics for 7-21 days. During the acute phase of urinary-tract infection, scintigraphy with technetium-99m-dimercaptosuccinic acid (DMSA) and ultrasonography were done. Voiding cystourethrography was undertaken at least 6 weeks after the end of antibiotic treatment. When scintigraphy showed renal parenchymal lesions, repeat scintigraphy was done after at least 2 months to assess the progression of renal lesions. For the analysis, children were grouped by age according to presumed risk of renal sequelae after pyelonephritis: high risk (< 1 year), moderate risk (1-5 years), low risk (> 5 years). FINDINGS: 201 patients were enrolled in the study (119 < 1 year, 47 aged 1-5 years, 35 > 5 years). During the acute phase of urinary-tract infection, renal lesions were found in 66 (55%) infants under 1 year, in 37 (79%) children aged 1-5 years, and in 24 (69%) children older than 5 years. Of these 127 children, 108 underwent repeat scintigraphy after an average of 3 months (50 < 1 year, 36 aged 1-5 years, 22 > 5 years). Overall, renal scars were found on repeat scintigraphy in 20 (40%) infants under 1 year, in 31 (86%) children aged 1-5 years, and in 14 (64%) children older than 5 years. 38 (36%) of these 65 patients had vesicoureteric reflux. Among 88 children who had a first documented urinary-tract infection and underwent repeat scintigraphy, renal scars were found in 20 (43%) under 1 year, in 26 (84%) aged 1-5 years, and in eight (80%) older than 5 years. INTERPRETATION: This study did not confirm the conventional view that the risk of renal scars after pyelonephritis diminishes with age. We believe that all children, irrespective of age, will benefit from any measure that prevents the development of renal sequelae.

Renal handling of carnitine in ill preterm and term neonates.

OBJECTIVE: To investigate the renal handling of carnitine in preterm and term ill neonates. METHODS: We studied the fractional tubular reabsorption of carnitine and the proximal renal tubular function of infants in the first week of life who were receiving very little or no carnitine in their diets. RESULTS: Mean plasma levels were low: total carnitine was 16.4 +/- 7.0 mumol/L, free carnitine was 9.2 +/- 5.0 mumol/L, and acylcarnitine was 7.2 +/- 4.1 mumol/L. The most premature group of neonates (gestation age, 26 to 31 weeks) had a fractional tubular reabsorption rate of free carnitine of 94.3% +/- 3.3%, which was lower than in the other two groups (98.1% +/- 2.4% for gestational age 32 to 36 weeks, p = 0.001; and 99.2% +/- 0.6% for gestational age 37 to 42 weeks, p = 0.002). In all patients the fractional tubular reabsorption of acylcarnitine was lower than that of free carnitine, indicating possible tubular secretion of acylcarnitine. It correlated with the total plasma carnitine levels (r = 0.53; p = 0.002). The fractional tubular reabsorption of free carnitine also correlated with gestational age (r = 0.60; p < 0.001). CONCLUSIONS: Ill neonates have a fractional tubular reabsorption rate of free carnitine within the normal range. It increases with gestational age, and has the same maturation rate as the other known indexes of proximal tubular function.

Endogenous TNF-alpha modulates the proliferation of rat mesangial cells and their prostaglandin E2 synthesis.

Mesangial cells (MC) are one cellular source of tumor necrosis factor alpha (TNF) within the kidney as shown by experimental stimulation with endotoxin. TNF was shown to increase MC synthesis of prostaglandins E2 (PGE2) which down regulate MC proliferation. The involvement of endogenous TNF as an autocrine factor to control MC proliferation is unknown. This role was evaluated in vitro by addition of anti-TNF immunoglobulins and soluble TNF receptor-I (sTNF-RI) on rat MC. Anti-TNF immunoglobulins and sTNF-RI induced a dose-dependent increase of cell proliferation when the cells were quiescent in 0.5% FCS P = 0.002). No effect was found when the cells were growing in 10% FCS (P = 0.113). Incubation of MC with anti-TNF immunoglobulins resulted in a dose-dependent decrease of PGE2 release. In order to investigate if the effect of TNF on MC proliferation was mediated by the decrease of PGE2 release, PGE2 was added to the culture medium at concentrations of 0.1 to 10 micrograms/ml in conjunction with anti-TNF immunoglobulins. PGE2 did not modify the proliferation induced by anti-TNF immunoglobulins. We conclude that anti-TNF immunoglobulins and sTNF-RI promoted MC DNA synthesis and influenced their PGE2 release by blocking the endogenous TNF. The mechanism of action on DNA synthesis was not mediated by PGE2. This indicates that endogenous TNF has a substantial role in the control of resting mesangial cells.

Cortical scintigraphy in the evaluation of renal parenchymal changes in children with pyelonephritis.

We designed a prospective study to evaluate the ability of dimercaptosuccinic acid cortical scintigraphy and ultrasonography to detect renal parenchymal lesions in children with pyelonephritis. One hundred eleven patients 1 week to 16 years of age (median 5.5 months) with a urine culture positive for pathogens were included in the study; cortical scintigraphy and ultrasonography were repeated in 25 children after a mean follow-up of 10.5 months. Cortical scintigraphy showed renal changes in 74 children (67%), and ultrasonography showed renal changes in 39 (35%) (p < 0.001); results of the two examinations were discordant in 49 patients (kappa = 0.19). Children more than 1 year of age had a higher incidence of renal lesions than did younger children (85% vs 66%; p = 0.04). The presence of inflammatory signs (erythrocyte sedimentation rate or C-reactive protein) had an 89% sensitivity and a 25% specificity in identifying renal lesions. Among children with renal changes, vesicoureteric reflux was present in 39%. At follow-up examination, 16 children (64%) had scars. Thus we found a high incidence of renal involvement in children with pyelonephritis. We found that cortical scintigraphy is more sensitive than ultrasonography in detecting renal changes, and we believe that it should be added to the initial examination of children with suspected pyelonephritis.

Three cases of neonatal herpes simplex virus infection presenting as fulminant hepatitis.

We report three cases of neonatal herpes simplex virus (HSV) infection presenting as fulminant hepatitis. None of the patients had clear risk factors for HSV infection and they all died. Antiviral treatment for HSV is currently available but must be administered early in the course of the disease before irreversible liver tissue damage is present. Since the diagnosis may be difficult to establish, we wish to draw the attention of clinicians to the presentation of neonatal HSV infection and suggest that in such cases viral cultures, including culture of liver tissue, should be obtained early and antiviral treatment administered while awaiting the culture results.