Autoimmune polyglandular syndrome type I can have significant kidney disease in children including recurrence in renal allograft - a report of two cases.

Background: Autoimmune polyglandular syndrome type 1 (APS 1) is an autosomal recessive disorder characterized by immune injury of multiple organ systems (primarily endocrine) secondary to a mutation in the autoimmune regulator (AIRE) gene. In some cases, patients develop tubulointerstitial nephritis (TIN) and progress to end-stage renal failure (ESRD).

Case Diagnosis/treatment: We describe two patients with APS 1 and TIN.

Autosomal dominant pseudohypoaldosteronism type 1: mechanisms, evidence for neonatal lethality, and phenotypic expression in adults.

Autosomal dominant pseudohypoaldosteronism type 1 (adPHA1) is a rare condition that is characterized by renal resistance to aldosterone, with salt wasting, hyperkalemia, and metabolic acidosis. It is thought of as a mild disorder; affected children's symptoms respond promptly to salt therapy, and treatment is not required after childhood. Mutations in the mineralocorticoid receptor gene (MR) cause adPHA1, but the long-term consequences of MR deficiency in humans are not known.

The anion gap (AG): studies in the nephrotic syndrome and diabetic ketoacidosis (DKA).

Although "unmeasured" anions contribute to metabolic acidosis in a variety of disease states, they are generally not measured directly but estimated from the calculation of "gaps." Among the most commonly used method, the anion gap (AG) is not only a function of "unmeasured" anions, but also it is a function of plasma non-carbonate buffers (albumin and phosphate), the plasma pH, and the method of measurement. To clarify the contribution of non-carbonate buffers to the AG, the Figge-Fencl-Waston model of human plasma was applied to laboratory values obtained from two novel populations, patients with nephrotic syndrome and patients with diabetic ketoacidosis (DKA).

An analysis of renal tubular acidosis by the Stewart method.

Renal tubular acidosis (RTA) comprises a group of disorders characterized by a low capacity for net acid excretion and persistent hyperchloremic, metabolic acidosis. To investigate the role of chloride, we performed hypotonic (0.45%) saline-loading experiments in 12 children with alkali-treated distal RTA (dRTA) and compared the results with data obtained from 17 healthy control subjects.

Bench-to-bedside review: Fundamental principles of acid-base physiology.

Complex acid-base disorders arise frequently in critically ill patients, especially in those with multiorgan failure. In order to diagnose and treat these disorders better, some intensivists have abandoned traditional theories in favor of revisionist models of acid-base balance. With claimed superiority over the traditional approach, the new methods have rekindled debate over the fundamental principles of acid-base physiology.

Stewart and beyond: new models of acid-base balance.

The Henderson-Hasselbalch equation and the base excess have been used traditionally to describe the acid-base balance of the blood. In 1981, Stewart proposed a new model of acid-base balance based upon three variables, the "strong ion difference" (SID), the total weak acids (ATot), and the partial pressure of carbon dioxide (Pco2). Over 20 years later, Stewart's physiochemical model still remains largely unknown.

Plasmapheresis treatment for recurrent focal sclerosis in pediatric renal allografts.

Recurrence of focal segmental glomerulosclerosis (FSGS) in pediatric renal allografts is associated with a poor graft survival. This study reports on plasmapheresis for the treatment of recurrent FSGS in pediatric renal transplant recipients. The records of 100 consecutive pediatric (age <21 years) renal transplants were reviewed.

New Jersey Caucasian, African American, and Hispanic population data on the PCR-based loci HLA-DQA1, LDLR, GYPA, HBGG, D7S8, and Gc.

New Jersey Caucasian, African American, and Hispanic genotype and allele frequencies were determined for the six PCR-based loci, HLA-DQA1, LDLR, GYPA, HBGG, D7S8, and Gc. All but one locus (HLA-DQA1 for African Americans) meet Hardy-Weinberg expectations. However, observing one departure in 18 loci over the three New Jersey sample populations is not unexpected.

Urine cytology and the diagnosis of renal allograft rejection. II. Studies using immunostaining.

Background: Urine immunocytology may provide a noninvasive method of investigating the antigens expressed by renal tubular cells. In previous investigations of patients with acute renal allograft rejection (AR), we showed that the adhesion molecule ICAM-1 is expressed by voided tubular cells. The up-regulation of ICAM-1, in turn, may be due to high circulating levels of interferon-gamma and/or TNF-alpha.

Urine cytology and the diagnosis of renal allograft rejection. I. Studies using conventional staining.

Objective: To determine the reproducibility and validity of urine cytology for the diagnosis of acute renal allograft rejection (AR).

Study Design: We conducted a blind, prospective study of 10 renal allograft recipients. Freshly voided aliquots of urine were obtained on each hospital day and at each outpatient visit for a mean of 52.

Urine cytology: an underused method to diagnose acute renal allograft rejection.

In children, the early detection and accurate diagnosis of acute renal allograft rejection (AR) may be difficult. A delay in the diagnosis and treatment of AR might engender a poor outcome. Core needle biopsy is diagnostic but invasive.

Evaluation of independence assumptions for PCR-based and protein-based genetic markers in New Jersey Caucasians.

Allele frequencies for six PCR-based loci and three protein-based (i.e., enzyme systems) loci were determined in a Caucasian sample population from New Jersey.

Improved renal allograft survival in children treated with FK 506 (tacrolimus) rescue therapy.

FK 506 has been reported to be effective in reversing acute renal allograft rejection that is resistant to steroids and to OKT3. The contribution of FK 506 "rescue" therapy to long-term graft survival has not been determined. We report 23 children transplanted between January 1993 and December 1994, 10 of whom received FK 506 "rescue" therapy.

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.

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.

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.

Role of intracellular phosphate in the regulation of renal phosphate transport during development.

Direct correlations have been observed between the renal intracellular concentration of phosphate ([Pi]i) and postnatal age (3-13 weeks in rats, 1-4 weeks in guinea pigs), as well as between the dietary supply of Pi and [Pi]i. In turn, [Pi]i was found to be inversely correlated with the renal tubular transport of phosphate (TRPi). However, age- and diet-related differences in [Pi]i alone do not explain the high capacity of Na(+)-Pi cotransport present in the kidney of the neonate.

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.

Case report 668. Carbonic anhydrase II deficiency syndrome (osteopetrosis associated with renal tubular acidosis and cerebral calcification).

A 4-month-old infant with bronchiolitis was found to have hyperdense bones on chest roentgenograms. The diagnosis of osteopetrosis was demonstrated by generalized increased radiological bone density and by a bone biopsy showing persistence of calcified cartilage. The infant also had a mixed proximal and distal renal tubular acidosis requiring as much as 12 mEq/kg per day of sodium bicarbonate.