Serum beta2-microglobulin and immunoglobulin levels in young hemodialysis patients.

Amyloidosis is a complication of long-term hemodialysis treatment. The major histological feature of hemodialysis-associated amyloidosis (HAA) is the deposition of amyloid fibrils in the affected lesions, due, in part, to elevated serum beta2-microglobulin (beta2M) levels. In vitro studies reveal that serum immunoglobulin light and heavy chains co-deposit with beta2M in tissues affected by HAA. Only one study of HAA has been performed in young dialysis patients. We therefore assessed risk factors for HAA in a group (n=30) of young (18.7+/-0.9 years) patients receiving chronic, uninterrupted hemodialysis using cellulose acetate membranes. All patients initiated dialysis before reaching 18 years of age. The pre-dialysis serum beta2M level was 49.7+/-3.9 mg/l (normal 0-2.4 mg/l). Since serum albumin was normal (4.3+/-0.1 mg/dl) and serum protein/albumin was elevated (1.7+/-0.0, normal 1.2-1.5), indicating increased circulating protein, we assayed immunoglobulins in the same patients. The serum immunoglobulin levels (expressed as a percentage of the total level of serum proteins) were elevated (21.3+/-0.9%, normal 11.1%-21.0%). The Kt/v was 1.37+/-0.03, suggesting that the high levels of serum beta2M and immunoglobulins were not due to inadequate dialysis in these patients. Patients with residual renal function (Kr) did display significantly lower serum levels of beta2M (33.2+/-2.3, P=0.03). Furthermore, improved clearance of beta2M correlated with higher values of Kr (r=0.914). In contrast, serum levels of immunoglobulin (22.6+/-3.7, P=0.5) were unaffected by Kr. In addition, there was no correlation between older age at onset of dialysis and serum levels of either beta2M (r=0.107) or immunoglobulins (r=0.321). Finally, the length of time on dialysis had no effect on serum levels of either beta2M (r=0.105) or immunoglobulins (r=0.092). Taken together, these results indicate that young hemodialysis patients may be at risk for HAA.

Acquired renal cystic disease in children and young adults on maintenance dialysis.

Acquired renal cystic disease (ARCD) is a well-known complication of end-stage renal disease (ESRD). We studied 24 patients, aged 8-27 years (mean 19.8 +/- 5.3 years), on chronic maintenance dialysis in our service. The duration of dialysis ranged between 13 and 192 months (mean 77.8 +/- 44.3 months). High-resolution ultrasonography revealed ARCD in 11 (45.8%) patients. No cysts were seen in 7 (29.1%) patients and solitary cysts in one or both kidneys were seen in 6 (25%) patients. Renal malignancy was diagnosed in 2 patients. One, 15 years old, had renal cell carcinoma after being on dialysis for 6 years. She did well after bilateral nephrectomy, left salpingo-oophorectomy, and regional lymphadenectomy. The second patient, 23 years old, had been on dialysis for 16 years when she developed renal oncocytoma. She died of congestive cardiomyopathy 6 months later. We conclude that ARCD is common in children and young adults with ESRD. Neoplastic transformation, although rare, is a potential complication. Annual follow-up with ultrasonography with selective use of computed tomography or magnetic resonance imaging is advised.

Joubert syndrome associated with multicystic kidney disease and hepatic fibrosis.

There are several diseases characterized by renal cysts and neurological abnormalities. Joubert syndrome is distinguished by hypoplasia of the cerebellar vermis, hypotonia, retinal dystrophy characterized by abnormal eye movements, and impaired psychomotor development, together with abnormal respiratory pattern. We describe a boy with Joubert syndrome associated with multicystic renal dysplasia and hepatic fibrosis. We speculate that the association of malformations of the renal and nervous systems in this syndrome and others are not random. Concomitant malformations of these systems are likely based upon their common developmental and genetic features.

Growth in children with moderate renal insufficiency: measurement, evaluation, and treatment.

Essential in the treatment of children with chronic renal insufficiency (CRI) is the elimination of growth deficits. With the prospect of recombinant human growth hormone (rhGH) and other adjunct treatment, the appropriate measurement and assessment of growth retardation and growth recovery will document continued progress toward eliminating this disabling condition. Phases and determinants of growth at different ages are best described by growth velocity patterns. Nutritional, hormonal, and metabolic determinants interact throughout each phase of growth. Potential for growth loss and recovery is greatest during infancy and early childhood, as shown by the growth velocity index (GVI) of change in height standard deviation score (SDS) (deltaHt - SDS) divided by the growth velocity - SDS (GV - SDS) (GVI = deltaHT - SDS/GV - SDS). An appropriate target height based on potential from mid-parental heights should be set before intervention to establish goals for duration of treatment. Ultimate adult height is the only true measurement of outcome, although predictive formulas based on parental heights and bone age versus chronologic age (BA/CA) are mathematic tools to gauge the efficacy of ongoing regimes. True catch-up growth is defined as the full recovery of lost percentiles and cannot be assumed with an increase in growth velocity or incremental gain in Ht-SDS.

Renal allograft rejection in children and young adults: the Banff classification.

In the Banff classification, arteritis and tubulitis are regarded as the principal histological lesions indicating acute renal allograft rejection. To test this claim, we examined 51 biopsies obtained from 21 children and young adults with transplant rejection. Two reviewers, blind to the clinical course, graded the biopsies according to the Banff scheme. In patients without significant tubulitis (borderline changes), rejection tended to be reversed easily (88%), often with methylprednisolone pulse (52%). In patients with arteritis or significant tubulitis (Banff I-III), rejection was reversed in only 23% (P < 0.001), in 9% with steroids, and in 14% with OKT3. Salvage of the graft was achieved in 26 of 35 (74%) with a score < 5 but in only 1 of 12 (8%) with a score > or = 5 (P < 0.001). All 6 patients with vasculitis lost their grafts despite methylprednisolone pulse and OKT3. We conclude that the Banff classification predicts accurately the outcome of renal allograft rejection in children and may aid in choosing appropriate therapy.

Analysis of adhesion molecule expression by tubular epithelial cells using urine immunocytology.

On their surface, renal tubular cells present intercellular adhesion molecule-1 (ICAM-1) during acute renal allograft rejection. We propose that the extent of ICAM-1 expression by renal tubular cells can be estimated from urine immunocytology. To test this hypothesis, we obtained 52 samples of urine from 31 renal transplant recipients with either acute tubular necrosis, rejection or stable renal function. Cytocentrifuged aliquots of urinary sediment were incubated with monoclonal antibodies to ICAM-1 in an avidin-biotin-peroxidase technique. To corroborate our findings, biopsy specimens were obtained for conventional and immunohistology one hour following vascular anastomosis and during rejection episodes. The proportion of renal tubular cells that expressed ICAM-1 was low in patients with acute tubular necrosis (23.8 +/- 3.6%) and high in patients with rejection (53.1 +/- 4.4% [SEM]) (P < .001). In 11 patients who recovered from rejection, the proportion of ICAM-1-positive renal tubular cells decreased from 55.9 +/- 5.6% to 25.5 +/- 4.3% (P < .05). In two patients who initially had acute tubular necrosis and then rejected their transplants, the expression of ICAM-1 on renal tubular cells tended to increase (from 27.5 +/- 2.5% to 60.0 +/- 20.0%, P = .12). In eight patients with acute tubular necrosis who never rejected their transplants, ICAM-1 expression remained low (23.1 +/- 3.8%). Immunocytology correlated well with immunohistology and the clinical diagnosis. Our findings suggest that urine immunocytology may be useful in monitoring adhesion molecule expression by renal tubular cells.

Sequential occurrence of IgA nephropathy and Henoch-Schönlein purpura: support for common pathogenesis.

We report a patient who developed Henoch-Schönlein purpura (HSP) 13 years after he presented with IgA nephropathy (IgAN). In both HSP and IgAN renal biopsy most commonly reveals focal proliferative glomerulonephritis on light microscopy and immunofluorescence displays mesangial IgA deposits. In addition, patients with HSP or IgAN have elevated serum IgA levels, circulating IgA immune complexes, IgA-bearing lymphocytes, immunoglobulin-producing cells, and binding of IgG to glomerular components of similar molecular weight. The occurrence of both diseases in the same patient or the same families and the presence of immune abnormalities compatible with HSP or IgAN in relatives of patients with these diseases suggest a common pathogenesis.

Proposal to establish a National Institute of Kidney and Urologic Diseases: a report of the National Kidney and Urologic Diseases Advisory Board.

In 1990, the National Kidney and Urologic Diseases Advisory Board published a long-range plan entitled "Window on the 21st Century." In that plan, the Board recommended that Congress establish a new National Institute of Kidney and Urologic Diseases (NIKUD). This recommendation stemmed from the Board's appreciation that patient morbidity and mortality from kidney and urologic diseases continue to increase and that a focused, well-funded research endeavor is the only real hope for reversing this trend. In 1992, the Board established a special subcommittee to further consider the establishment of NIKUD. The subcommittee sought input from a wide variety of extramural and intramural sources. The American Urologic Association felt that a new devoted institute would provide coordination and expansion of basic research into kidney and urologic diseases, which is presently fragmented and underfunded within multiple institutes. The research areas of kidney and urologic diseases are not currently receiving adequate or appropriate attention proportionate to their prevalence and their adverse impact on society. The American Society of Nephrology supports the establishment of a separate kidney and urology institute. First and foremost, our primary interest is to obtain more support for kidney and urologic diseases. Such research does not receive the emphasis and prominence that it deserves at the National Institutes of Health. The American Society of Nephrology believes that a separate institute would provide increased focus for these diseases.(ABSTRACT TRUNCATED AT 250 WORDS)

Proposal to establish a National Institute of Kidney and Urologic Diseases--a report of the National Kidney and Urologic Diseases Advisory Board.

In 1990, the National Kidney and Urologic Diseases Advisory Board published a long-range plan entitled "Window on the 21st Century." In that plan, the board recommended that Congress establish a new National Institute of Kidney and Urologic Diseases (NIKUD). This recommendation stemmed from the board's appreciation that patient morbidity and mortality from kidney and urologic diseases continue to increase and that a focused, well-funded research endeavor is the only real hope for reversing this trend. In 1992, the board established a special subcommittee to further consider the establishment of a NIKUD. The subcommittee sought input from a wide variety of extramural and intramural sources. American Urologic Association--a new devoted institute would provide coordination and expansion of basic research into kidney and urologic diseases, now fragmented and underfunded within multiple institutes. The research areas of kidney and urologic diseases are not currently receiving adequate or appropriate attention proportionate to their prevalence and their adverse impact upon society. The American Society of Nephrology (ASN) supports the establishment of a separate kidney and urology institute. First and foremost, our primary interest is to obtain more support for kidney and urologic diseases. Such research does not receive the emphasis and prominence that it deserves at the National Institutes of Health. ASN believes that a separate institute would provide increased focus for these diseases. National Kidney Foundation (NKF)--the creation of such an institute is the highest priority of the medical and lay constituencies of the NKF.(ABSTRACT TRUNCATED AT 250 WORDS)

The fractional excretion of urea: a new diagnostic test for acute renal allograft rejection.

Fractional excretion of sodium (FENa) has been used in the diagnosis of acute renal allograft failure on the assumption that poor allograft perfusion should result in a low FENa. However, many patients receive medications which affect the active transport of Na+ and thus FENa. In contrast, the fractional excretion of urea (FEurea) is mostly dependent on passive forces and is therefore less influenced by drug therapy. To test the hypothesis that FEurea might be more useful than FENa in evaluating graft failure, we compared FEurea with FENa during 79 episodes of acute renal allograft dysfunction due to acute rejection (AR), cyclosporine nephrotoxicity (CsA-Nx), viral infection, or bacterial infection in 32 children and young adults with renal transplants. There was no significant difference between groups in FENa. However, FEurea was significantly lower (P < 0.05) in patients with CsA-Nx (32.6 +/- 1.9%) and viral infection (32.9 +/- 3.2%) than those with AR (45.1 +/- 1.7%) or bacterial infection (38.9 +/- 2.5%). FEurea was < 35% in 20 of 28 (71.4%) episodes of CsA-Nx and 8 of 11 (72.2%) of viral infection, but only 5 of 36 (13.9%) of AR (P < 0.05). FEurea was also measured during stable graft function, 7-14 days prior to allograft dysfunction. CsA-Nx was associated with a 30.5 +/- 8.3% decrease in FEurea. FEurea did not change in patients with AR. Based on these findings, we present an algorithm to aid in the differential diagnosis of acute renal allograft failure.

The 1989 report of the North American Pediatric Renal Transplant Cooperative Study.

This report of the North American Pediatric Transplant Cooperative Study summarizes data contributed by 57 participating centers on 754 children with 761 transplants from 1 January 1989 to 16 February 1989. Data collection was initiated in October 1987 and follow-up of all patients is ongoing. Transplant frequency increased with age; 24% of the patients were less than 5 years, with 7% being under 2 years. Common frequent diagnoses were: aplastic/dysplastic kidneys (18%), obstructive uropathy (16%), and focal segmental glomerulosclerosis (12%). Preemptive transplant, i.e., transplantation without prior maintenance dialysis, was performed in 21% of the patients. Dialytic modalities pretransplant were peritoneal dialysis in 42% and hemodialysis in 25%. Bilateral nephrectomy was reported in 29%. Live-donor sources accounted for 42% of the transplants. Among cadaveric donors, 41% of the donors were under 11 years old. During the first post-transplant month, maintenance therapy was used similarly for live-donor and cadaver source transplants, with prednisone, cyclosporine, and azathioprine used in 93%, 83%, and 81%, respectively. Triple therapy with prednisone, cyclosporine, and azathioprine was used in 78%, 75%, and 75% of functioning cadaver source transplants at 6 months, 12 months, and 18 months as opposed to 60%, 63%, and 54% for live-donor procedures, with single-drug therapy being uncommon. Rehospitalization during months 1-5 occurred in 62% of the patients, with treatment of rejection and infection being the main causes. Additionally, 9% were hospitalized for hypertension. During months 6-12 and 12-17, 30% and 28% of the patients with functioning grafts were rehospitalized. Times to first rejection differed significantly for cadaver and live-donor transplants. The median time to the first rejection was 36 days for cadaver transplants and 156 days for live-donor transplants. Overall, 57% of treated rejections were completely reversible although the complete reversal rate decreased to 37% for four or more rejections. One hundred and fifty-two graft failures had occurred at the time of writing, with a 1-year graft survival estimate of 0.88 for live-donor and 0.71 for cadaver source transplants. In addition to donor source, recipient age is a significant prognostic factor for graft survival. Among cadaver donors, decreasing donor age is associated with a decreasing probability of graft survival. Thirty-five deaths have occurred; 16 attributed to infection and 19 to other causes. The current 1-year survival estimate is 0.94. There have been 9 malignancies.

Elusive vesicoureteral reflux in children with normal contrast cystograms.

Recurrent pyelonephritic episodes in children with normal contrast cystograms pose a difficult management problem, since the lack of demonstrable reflux adversely affects the treatment. A total of 10 children with clinical symptoms of pyelonephritis in whom normal contrast cystograms had been performed properly subsequently had significant degrees of reflux detected by isotope cystography. These findings indicate that isotope cystography should be included in the evaluation of patients with pyelonephritis in whom reflux is not confirmed by conventional contrast medium techniques.

Clinical manifestations of herpesvirus infections in pediatric renal transplant recipients.

We report our experience with 29 symptomatic herpesvirus infections occurring during the course of 87 pediatric transplant procedures performed over the 10-year period, 1973 to 1982. The yearly attack rate ranged from 0.05 to 0.40 case per cumulative patient years at risk. A greater proportion (9 of 14) of children who received more than 10 units of whole blood or packed red blood cells prior to transplantation developed a viral infection compared with those given 10 transfusions or fewer (8 of 25) (P = 0.10). Fever occurred in 22 (76%) children, pulmonary disease in 8 (28%), hepatitis in 11 (35%), leukopenia in 7 (24%), thrombocytopenia in 9 (31%) and central nervous system disease in 3 (10%). Herpesvirus infections were responsible for allograft loss in 7 (24%) patients. However, no differences in the actuarial graft survival curves were noted for transplants performed since 1979 in children with and without viral infection. The etiologic viral agents were cytomegalovirus in 19 (65%) episodes, herpes simplex virus in 8 (28%), Epstein-Barr virus in 2 (7%) and varicella-zoster virus in 2 (7%). Cytomegalovirus-infected patients were younger and more commonly developed primary infection compared with children with herpes simplex virus disease who were more likely to have secondary infection and to manifest a mucocutaneous vesicular rash. We conclude that the etiologic agents and clinical features of herpesvirus infections are similar in pediatric and adult renal allograft recipients. Moreover except for distinctive syndromes such as mucocutaneous vesicular eruption or a central nervous system lymphoma, the various herpes-viruses cause clinically indistinguishable illnesses in pediatric transplant patients with similar end organ involvement and untoward renal consequences.