Retransplantation after post-transplant lymphoproliferative disease

We present a boy who developed post-transplant lymphoproliferative disease (PTLD) 3.5 months after a first kidney transplant. The diagnosis was made after histopathological examination of the renal graft which was removed because of Pseudomonas aeruginosa septicaemia. After 2 years on dialysis, the patient received a second renal transplant. This graft continues to function after 5 years and there has been no evidence of recurrence of PTLD. This suggests that retransplantation can be undertaken in patients who have recovered from PTLD in a previous graft. Received March 25, 1996; received in revised form October 10, 1996; accepted October 18, 1996     

Increased urinary catecholamines in a hypertensive child with renal artery stenosis

We report a hypertensive child with renal artery stenosis who exhibited increased urinary excretion of norepinephrine (NE) and normetanephrine (NMN), while vanillylmandelic acid (VMA) excretion was within the normal range. The NMN values prompted us to investigate the patient for pheochromocytoma; for this purpose, NE was determined by plasma catecholamine assays in venous samples obtained by catheterization. The moderately increased NE levels could not be localized to any particular sampling site. Arteriography demonstrated right renal artery abnormalities. Following right nephrectomy with preservation of the right adrenal gland, arterial blood pressure returned to normal. The cause of increased NMN excretion without a concomitant rise in VMA during hypertension is discussed. Received May 23, 1995; received in revised form and accepted February 6, 1996     

Bilateral renal venous thrombosis in a neonate associated with resistance to activated protein C

Renal venous thrombosis (RVT) is a serious complication of neonates. In most cases the underlying cause of RVT remains unclear. Here we report a neonate with bilateral RVT and adrenal haemorrhage associated with a heterozygous mutation of the gene encoding for clotting factor V, resulting in resistance to activated protein C. Vigorous thrombolytic therapy with urokinase followed by recombinant tissue plasminogen activator dissolved the thrombus in the inferior vena cava and restored perfusion of both kidneys. However, a haemorrhagic rupture of the right kidney occurred, requiring emergency nephrectomy. Despite reperfusion of the left kidney and resumption of urine output, the patient remained dialysis dependent. Due to persistent adrenal insufficiency, long-term substitution of hydrocortisone was necessary. The patient was prophylactically treated with coumarin during the first 6 months of life and is now waiting for renal transplant at the age of 1 year. Received January 19, 1996; received in revised form and accepted May 10, 1996     

Chronic anemia as a complication of parvovirus B19 infection in a pediatric kidney transplant patient

. This is a report of unexplained anemia that persisted for 4 months in an adolescent renal transplant patient receiving immunosuppression that included prednisone, tacrolimus, and mycophenolate mofetil. This patient required monthly blood transfusions for fatigue, palpitations, and hematocrit levels between 15% and 17%. In addition, his posttransplant course was notable for the development of insulin-dependent diabetes mellitus. While receiving low-dose prednisone, he was switched from tacrolimus to cyclosporin and tapered off insulin injections over the next 2 months. At 4.5 months post-transplantation, further diagnostic evaluation was suggestive of parvovirus B19 infection as the cause for our patient’s chronic anemia. After testing negative for serum-specific parvovirus B19 IgM and IgG antibodies, parvovirus B19 infection was detected in blood by the polymerase chain reaction. Treatment with intravenous immunoglobulin (1 g/kg per day × 2 days) resulted in normalization of both his reticulocyte count and hematocrit within 6 weeks. At 4 months after receiving the immunoglobulin infusion, he has maintained a normal hematocrit level and stable renal function without requiring further blood transfusions. Received August 23, 1996; received in revised form and accepted November 20, 1996     

Immunization practices in children with renal disease: a report of the North American Pediatric Renal Transplant Cooperative Study

 To determine the current immunization recommendations of practicing pediatric nephrologists, a questionnaire was sent to the members of the North American Pediatric Renal Transplant Cooperative Society. Sixty-two percent of the centers responded. The results of the survey suggest that although consensus for approaching immunization does exist, recommendations do vary from center to center. Virtually all centers recommend standard vaccines [DTP, oral poliovirus (OPV), hepatitis B (Hep B), and Haemophilus influenzae B (Hib)] for their renal insufficiency and dialysis patients. Despite the fact that they are not infectious, standard killed vaccines (DTP, Hep B, Hib) are recommended less frequently for transplanted patients (86%) than their renal insufficiency (98%) and dialysis (near 100%) counterparts. Additionally, OPV and measles/mumps/rubella (MMR), both live viral vaccines, are rarely recommended post transplant. Almost 90% of centers recommend the use of influenza vaccine, while only 60% of centers recommend pneumococcal vaccine for children with renal disease. Over 70% of centers recommend the newly licenced varicella vaccine for patients on dialysis and those with renal insufficiency. Between 5% and 12% of centers recommend live viral vaccines, including OPV, MMR, and varicella vaccine, for immunosuppressed patients post renal transplant. Received July 11, 1996; received in revised form and accepted November 19, 1996     

Effects of growth hormone on insulin-like growth factors and binding proteins before and after renal transplantation

A bstract. Three short children with severe chronic renal failure were treated with recombinant human growth hormone (rhGH) for 2 years. Each received a transplant in the 2nd year. Serum collected before and during rhGH therapy was analysed retrospectively by Western ligand blot and immunoblotting techniques. In addition, radioimmunoassays for insulin-like growth factor-I (IGF-I), IGF binding protein-3 (IGFBP-3), acid-labile subunit (ALS) and IGFBP-1 were performed. IGFBPs in serum, detected by Western ligand blot, were identified as IGFBP-3, -2, -1 and -4 by immunoblot. The serum concentration of IGF-I in each child rose approximately fourfold with rhGH before transplantation and subsequently remained elevated. IGFBP-3 levels rose to double the pretreatment value, but dropped to normal levels following transplantation, while ALS rose with rhGH treatment and remained increased after transplantation. IGFBP-1 levels changed little with rhGH but fell following transplantation. A low molecular weight form of IGFBP-3 was noted at 30 kilodaltons on immunoblot which was not clearly seen on the ligand blot. IGFBP-2 was present as a distinct band on Western ligand blot before transplantation and appeared decreased in intensity subsequently. IGFBP-1, seen on immunoblot clearly before transplant, disappeared after the transplant. rhGH successfully improved growth in these children, in association with a fourfold increase in IGF-I levels, which was maintained following transplantation. The reduction in IGFBPs following transplantation suggests correction of impaired clearance by the diseased kidney. Received September 5, 1994; received in revised form November 8, 1995; accepted November 21, 1995     

Excess prevalence of non diabetic renal disease in native American children in Manitoba

We undertook a 1-year prospective point prevalence study to test the hypothesis that there is an excess of non-diabetic renal disease in native American children; 29.6% (73/247) of the population attending the only regional pediatric nephrology clinic in 1993 were native compared with 8.2% of the Manitoba population in this age group (odds ratio = 4.4, P<0.001). Patients were classified as low risk (normal renal function, no deterioration expected), high risk (normal renal function, deterioration probable), or established chronic renal failure (creatinine clearance chronically low or post renal transplant). Patients were further classified as suffering from congenital renal anomalies, genetic or metabolic disease, or acquired renal disease. Odds ratios were calculated based on data from the Aboriginal Peoples’ Population Survey and Statistics Canada census data. The odds ratios for low-risk renal disease, high-risk renal disease, and chronic renal failure were 3.8, 5.6, and 6.3, respectively (P<0.001 in all categories). The odds ratios for congenital, genetic, or acquired disease were 4.5 (P<0.001), 0.9 (P = ns), and 6.1 (P<0.001), respectively. Native American children in Manitoba demonstrate increased prevalence of serious congenital and acquired renal disease. These children are also more likely to live in medically underserviced communities, long distances from tertiary care centers. This study emphasizes the importance of considering factors other than diabetes mellitus when considering the problem of renal disease in native Americans. Received November 17, 1995; received in revised form and accepted March 19, 1996     

Anti-glomerular basement membrane glomerulopathy in a young child

We report the youngest patient with anti-glomerular basement membrane disease described in the literature to date. Age-dependent expression of the target antigen in this auto-immune disease explains the low incidence in young children. Despite adequate immunosuppression, renal function did not recover in our patient. Received November 13, 1995; received in revised form and accepted March 20, 1996     

Absence of α6(IV) collagen in kidney and skin of X-linked Alport syndrome patients

Ab stract. To identify the abnormalities of the type IV collagen α6 chain, α6(IV), in Alport syndrome, we examined renal and skin tissue using rat monoclonal antibodies against non-consensus amino acid sequences of α6(IV). Immunofluorescence of normal human kidney and skin tissue revealed linear α6(IV) staining in the basement membrane (BM) of Bowman’s capsule, in some tubules, and also in the epidermal BM. Renal specimens from five male patients of four families with X-linked Alport syndrome showed no reactivity for α6(IV) in Bowman’s capsules and tubules. In these patients, α1(IV) and α2(IV) were normal, whereas α3(IV), α4(IV), and α5(IV) were absent from the BMs of the kidney. In skin tissue of male patients, neither α5(IV) nor α6(IV) were detected. The epidermal BM of female heterozygotes with X-linked Alport syndrome showed a mosaic staining for α5(IV) and α6(IV). These findings indicate that, in addition to a disturbed α3(IV)-α4(IV)-α5(IV) network, patients with X-linked Alport syndrome have abnormalities in α6(IV) of the renal and epidermal BMs at the protein level. Received October 6, 1995; received in revised form April 25, 1996; accepted April 29, 1996     

Nitric oxide in the developing kidney

Although nitric oxide (NO) has a well-established role in regulating renal function in the adult, recent studies point to perhaps an even more critical role for NO in maintaining basal renal blood flow (RBF) and glomerular filtration rate (GFR) in the developing kidney. The immature kidney has enhanced renal hemodynamic and functional responses to stimulation and inhibition of NO synthesis when compared with the adult, and these increased responses are not mediated by prostaglandins. Increased intrarenal activity of NO in the developing kidney counter-regulates the highly activated renin angiotensin system by modulating the angiotensin II-mediated vasoconstriction of the developing renal vasculature, the angiotensin II effects on GFR, as well as renin release. Localization studies demonstrate that NO acts on neonatal RBF and stabilization of GFR through an intrarenal distribution of the synthesizing enzyme, nitric oxide synthase, that is different from that of the adult. The developing kidney is dependent on NO to maintain RBF and GFR during periods of hypoxemia, protecting against renal injury, such as acute renal failure. In summary, NO is vital in the developing kidney to maintain normal physiological function and to protect the immature kidney during pathophysiological stress. Received February 12, 1996; received in revised form and accepted February 28, 1996     

Effect of growth hormone on urine calcium and serum vitamin D metabolites in renal failure

A bstract. Growth hormone (GH) causes a modest increase in urine calcium excretion in normal adults, but uremic rats given both GH and calcitriol developed hypercalciuria. Ten short prepubertal children with renal insufficiency treated with recombinant human GH (rhGH) had urine calcium to creatinine (Ca/Cr) ratios and serum vitamin D metabolite concentrations monitored prospectively for up to 24 months. Six were also treated with calcitriol and two with other vitamin D preparations. Mean urine Ca/Cr ratios or mean serum concentrations of 1,25-dihydroxy vitamin D, 24,25-dihydroxy vitamin D, and 25-hydroxy vitamin D did not change significantly during treatment with rhGH. The risk for rhGH-induced hypercalciuria is small in children with renal insufficiency, even when treated concomitantly with a vitamin D preparation. Received January 12, 1994; received in revised form and accepted December 29, 1995     

Catch-up growth in children with vesico-ureteric reflux

A longitudinal retrospective study of height Z score (HZ score) and weight-for-height index (WHI) was performed on 94 pre-pubertal children with vesico-ureteric reflux (VUR) and normal creatinine clearance followed for 1 – 6.8 years (mean 3.1 years). Thirty patients had bilateral VUR with scintigraphic signs of renal scarring (B+), 17 had bilateral VUR without renal scarring (B – ), 27 had unilateral VUR with (U+) and 20 unilateral VUR without (U – ) renal scarring. Thirty-three patients received only antimicrobial medication and 61 underwent successful antireflux operation. The increase in HZ score and WHI during the 1st year of follow-up was significantly (P = 0.001 and 0.00003, respectively) higher than during the 2nd year. At first visit, B+ subjects had an average WHI and HZ score that were significantly (P = 0.02 and 0.04, respectively) lower than the other groups of patients together. At last visit this difference was not significant. In B+ subjects, the WHI and HZ score at last visit were significantly (P = 0.04 for both) higher than at the first visit. B+ patients fully recover their body growth deficit compared with other groups of VUR subjects after medical and/or surgical therapy. Received February 23, 1996; received in revised form and accepted June 24, 1996     

Use of pump-assisted hemofiltration in children with acute renal failure

In critically ill children, acute renal failure (ARF) is associated with a high mortality. To assess the outcome and complications of pump-assisted hemofiltration (PAHF) using a standard volumetric pump to regulate blood flow, we retrospectively reviewed our experience in 52 patients with ARF treated with PAHF from 1989 to 1995. These patients ranged in age from <1 month to 19 years and in weight from 2 to 125 kg. The most common underlying diagnoses were congenital heart disease and infection. The duration of PAHF averaged 9±8 days (range 24 h to 43 days). Hemodiafiltration for solute control was required in 40 patients. Total fluid intake while on PAHF was 136±95 ml/kg per day, while urine output and ultrafiltration averaged 15±24 ml/kg per day and 89±58 ml/kg per day, respectively. Management of laboratory abnormalities was efficient with only 4 patients requiring 1 or 2 additional treatments of hemodialysis for control of uremia. Complications included hyponatremia in 13 patients, hypokalemia in 14 patients, hypovolemia in 8 patients, hyperglycemia in 6 patients, and bleeding in 9 patients. No complications specifically related to use of the volumetric infusion pump for PAHF were noted. PAHF using a volumetric infusion pump for blood flow regulation in critically ill children with ARF is a practical and efficient therapy. Received April 16, 1996; received in revised form September 13, 1996; accepted October 2, 1996     

A case of Pearson syndrome associated with multiple renal cysts

A 41-day-old infant who had severe metabolic acidosis, anemia, bleeding, hypoglycemia, and proximal tubulopathy was diagnosed with Pearson syndrome. Fibrosis in the liver, severe iron deposition in hepatocytes, and multiple renal cortical cysts were found on postmortem examination. Southern blot analysis of mitochondrial DNA obtained from peripheral blood revealed a heteroplasmic deletion of approximately 3.5 kilobases. Received October 5, 1995; received in revised form and accepted March 11, 1996     

Tubular proteinuria in reflux nephropathy: post ureteric re-implantation

We studied urine protein excretion in 55 adults with reflux nephropathy (median age 26.9 years) who had had normal blood pressure, renal function and ureteric re-implantation in childhood. Urine retinol binding protein (RBP), N-acetyl-β-D-glucosaminidase (NAG), albumin, bacteriuria, systolic blood pressure, glomerular filtration rate (GFR), peripheral plasma renin activity (PRA) and the degree of renal scarring were measured in each subject; 20 had bilateral and 35 unilateral renal scarring; 5 were hypertensive and none were in renal failure. Urinary NAG and RBP excretions were significantly greater in the study group than in 34 healthy controls (median age 29.7 years). Within the study group, NAG excretion significantly correlated with PRA (P = 0.02). RBP excretion correlated with PRA, systolic blood pressure and the laterality (bilateral vs. unilateral) of scarring (P<0.01). Urinary albumin excretion correlated with systolic blood pressure (P = 0.03). We conclude that increased urinary protein, especially NAG and RBP excretion, occur late after ureteric re-implantation in reflux nephropathy independent of GFR. Its association with PRA supports the concept of segmental perfusion and filtration as an important mechanism that may explain the above findings. Received June 26, 1995; received in revised form and accepted March 6, 1996     

Acute interstitial nephritis associated with IgA nephropathy in children

IgA nephropathy (IgAN) is a relatively common glomerulopathy in children and adolescents. The etiology of this disease is uncertain. We previously reported a child with IgAN who developed acute interstitial nephritis. We now describe three pediatric patients, including the index case, who had IgAN and who developed concomitant acute interstitial nephritis in association with renal functional impairment. We suggest that this histopathological lesion be considered in any child with IgAN and unexpectedly severe kidney dysfunction. Received January 19, 1996; received in revised form and accepted June 10, 1996     

Autosomal recessive polycystic kidney disease: long-term outcome of neonatal survivors

 Autosomal recessive polycystic kidney disease causes renal and hepatic dysfunction in childhood. We describe the clinical outcome of 52 children with this diagnosis born between 1950 and 1993. Currently 23 are alive, 24 dead and 5 have been lost to follow-up; 1 has been dialysed and 7 transplanted. Life-table analysis of the patients surviving the 1st month of life revealed an actuarial renal survival of 86% at 1 year and 67% at 15 years. The probability of requiring anti-hypertensive treatment was 39% at 1 year and 60% at 15 years of age. Bleeding from gastro-oesophageal varices occurred in 8 patients at a mean age of 12.5 years, and was preceded by haematological evidence of hypersplenism in 6 of them. The study indicates a relatively good prognosis for patients with this condition who survive the neonatal period and emphasises the importance of early detection and appropriate management of systemic and portal hypertension. Received May 17, 1996; received in revised form and accepted October 29, 1996     

Systemic lupus erythematosus presenting as congenital nephrotic syndrome

A male Caucasian infant developed nephrotic syndrome at 10 weeks of age. He had high titres of anti-nuclear antibody (ANA) and anti-double-stranded DNA antibody, with hypocomplementaemia, antiplatelet antibodies and anticardiolipin antibodies. There were no detectable antibodies to extractable nuclear antigens (ENA). His mother was consistently seronegative for anti-ENA (anti-Ro) antibodies and ANA. He developed severe, progressive multisystem involvement, however renal function has remained stable. Immunosuppression has been the mainstay of therapy in this rare presentation of systemic lupus erythematosus. Received December 6, 1995; received in revised form and accepted May 9, 1996     

Scanning and transmission electron-microscopic study of the development of the podocyte in the human fetus

The metanephric kidneys of seven human fetuses at 11 – 17 weeks’ gestation were examined by scanning and transmission electron microscopy in order to evaluate differentiation of glomerular podocytes. When glomeruli were in the stage of S-shaped bodies, the surface of the visceral epithelium of renal corpuscles was smooth, with indistinct cell borders. As the glomeruli developed, visceral epithelial cells of renal corpuscles became spherical and resembled clusters of grapes in dense aggregation. In this stage, processes and foot processes were simultaneously formed at the base of epithelial cells. As glomeruli further differentiated, visceral epithelial cells of renal corpuscles began to separate from one another and became flat with the development of vascular loops. Processes and foot processes were exposed for the first time in Bowman’s space. In this stage, the degree of differentiation of epithelial cells varied widely among various sites of the glomerulus. As glomeruli developed further, projections became more complex and epithelial cells began to show structures similar to those of adult epithelial cells. The adjacent foot processes arose from different cells throughout the period of morphological differentiation. Received August 21, 1995; received in revised form May 13, 1996; accepted June 17, 1996     

Incidence of microalbuminuria in children with pyelonephritic scarring

There is experimental evidence that loss of renal parenchyma results in hyperfiltration in the remnant glomeruli followed by development of glomerulosclerosis. Microalbuminuria, i.e., a urinary albumin excretion rate of 20 – 200 μg/min, is considered to be an early predictor of diabetic glomerulosclerosis. Hypothetically, increased urinary albumin excretion in patients with pyelonephritic scarring may also indicate glomerulosclerosis, with risk for future deterioration of renal function. This study was performed to determine the incidence of increased albumin excretion in children with mild to moderate pyelonephritic scarring, and to relate the information to glomerular filtration rate (GFR; clearance of inulin) and effective renal plasma flow (clearance of para-aminohippuric acid), as well as to the degree of scarring. The functional investigations were performed under water diuresis. Fifty-seven children, aged 1.7 – 17.9 years, with pyelonephritic renal scarring were included in the study. Nine young healthy adults were used as controls. The GFR was significantly lower in the children with pyelonephritic scarring than in the controls (median 93 ml/min per 1.73 m², range 48 – 133 vs. 111 ml/min per 1.73 m², range 89 – 121, P<0.05), and the urine albumin excretion was significantly higher (median 20 μg/min per 100 ml GFR, range 0.8 – 170 vs. 9.2 μg/min per 100 ml GFR, range 3.3 – 21, P<0.05). An inverse correlation was found between urine albumin excretion and GFR. Increased urine albumin excretion was found in 70% of the children with a GFR below 90 ml/min per 1.73 m² compared with 41% of the children with a GFR above this level. Increased urine albumin excretion (>20 μg/min per 100 ml GFR) was found in 51% of the children with pyelonephritic scarring, while only 14% had increased age-adjusted serum creatinine concentrations. The high incidence of microalbuminuria in children with pyelonephritic scarring indicates long-term follow-up until the ultimate outcome has been better defined. Received January 17, 1995; received in revised form and accepted April 2, 1996