Bernard Gauthier

Bartter syndrome and focal segmental glomerulosclerosis: a possible link between two diseases

Abstract We describe a patient with signs and symptoms of classic Bartter syndrome. The patient tested negative for all known genetic abnormalities associated with this tubular disorder. Proteinuria was found within 1 year after the diagnosis of Bartter syndrome. A renal biopsy performed 6 months later, when her kidney function was normal, revealed focal segmental glomerulosclerosis (FSGS). We propose a link between stimulation of the renin-angiotensin system and sclerotic changes in the glomerulus. This lesion may explain previous reports of kidney failure in patients with Bartter syndrome.

Vitamin E treatment of focal segmental glomerulosclerosis: results of an open-label study

Abstract Experimental data indicate that excessive production of reactive oxygen molecules contributes to progressive renal injury and that treatment with antioxidants attenuates this damage. Therefore, we investigated whether vitamin E supplementation could ameliorate renal disease and reduce proteinuria in children with a variety of kidney disorders. Vitamin E, 200 IU twice daily, was administered orally to 11 children with focal segmental glomerulosclerosis (FSGS) (group A) and 9 patients with miscellaneous kidney diseases (group B) [Henoch-Schönlein purpura nephritis (n=3), urinary tract anomalies (n=2), non-specific immune complex glomerulonephritis (n=2), IgA nephropathy (n=1), and reflux nephropathy (n=1)]. The duration of vitamin E treatment, when no other therapy was introduced, was 2.9±0.4 months. Proteinuria was determined by measuring the protein:creatinine ratio (mg/mg) in an early morning urine specimen. In children with FSGS, administration of vitamin E lowered the protein:creatinine ratio in 10 of 11 patients from 9.7±5.1 to 4.1±1.1 (P<0.005). In contrast, among children with miscellaneous renal diseases, vitamin E had no beneficial impact on urinary protein excretion-protein:creatinine ratio 2.5±1.0 pre versus 2.4±1.2 post antioxidant. Vitamin E supplementation had no effect on glomerular filtration rate, serum albumin, or cholesterol concentration in either group of patients. These findings suggest that reactive oxygen molecules may play a more-prominent role in causing renal injury in patients with FSGS than in other kidney disorders. Antioxidant therapy may be a useful adjunct in the treatment of children with FSGS and proteinuria that is refractory to standard medical management.

Angiotensin converting enzyme inhibitor therapy in children with Alport syndrome: effect on urinary albumin, TGF-β, and nitrite excretion

BackgroundAngiotensin converting enzyme inhibitors are routinely prescribed to patients with chronic kidney disease because of their known renoprotective effects. We evaluated the effect of short-term therapy with the angiotensin converting enzyme inhibitor, enalapril, in early Alport syndrome, defined as disease duration less than 10 years and a normal glomerular filtration rate.Methods11 children with early Alport syndrome were investigated. Two consecutive early morning urine specimens were collected at the start of the study for measurement of urinary creatinine, total protein, albumin, TGF-β, and nitrite excretion. Patients were treated with enalapril, ≅ 0.2 mg/kg/day, once a day for 14 days. Two early morning urine specimens were collected on days 13 and 14 of enalapril treatment and two weeks later for measurement of urinary creatinine, total protein, albumin, TGF-β, and nitrite excretion.ResultsPrior to treatment, urinary excretion of transforming growth factor-β and nitrite, the major metabolite of nitric oxide, was within normal limits in all patients. Administration of enalapril for 2 weeks did not alter urinary albumin, transforming growth factor-β, or nitrite excretion.ConclusionThese findings suggest that early Alport syndrome represents a disease involving exclusively intrinsic glomerular barrier dysfunction. At this stage of the illness, there is no evidence of angiotensin II-mediated proteinuria or increased production of transforming growth factor-β and, therefore, routine treatment with an angiotensin converting enzyme inhibitor may not be warranted.

Magnetic resonance imaging in acute pyelonephritis

Abstract. The diagnosis of acute pyelonephritis in children remains a clinical challenge. We assessed the feasibility of magnetic resonance imaging (MRI) detection of pyelonephritis in four pediatric patients and compared the results with renal cortical scintigraphy. MRI revealed areas of high signal intensity in the kidney that coincided with photon-deficient regions in the radionuclide scans in two children with acute pyelonephritis. These findings confirm work in experimental animals and indicate that MRI can accurately detect acute pyelonephritis in children.

Isolated Proteinuria in Children Natural History and Indications for Renal Biopsy

The significance of isolated proteinuria in pediatric patients is uncertain. Therefore, we retrospectively studied all children evaluated for this urinary abnormality during the 6-year period from 1986 to 1992. Thirty-one patients (19 males), age 2 to 20 years, were identified as having isolated proteinuria that had persisted for a mean interval of 9.6 ± 1.9 (SEM) months. The diagnosis was based upon the presence of a urine protein:creatinine ratio >0.2 in an early morning specimen. None of the patients had hematuria, edema, or azotemia. Seventeen children underwent a renal biopsy. There was no difference between the patients who were biopsied and those who were not with respect to age, magnitude of proteinuria, glomerular filtration rate (GFR), or serum albumin and cholesterol concentrations. The renal histopathology revealed focal segmental glomerulosclerosis (FSGS) (n = 8), membranous nephropathy (n = 1), postinfectious nephritis (n = 2), focal global glomerulosclerosis (FGGS) (n = 1), and normal kidney tissue (n = 5). Twelve of the patients who did not undergo a kidney biopsy and four of the five children with a normal renal biopsy were followed for at least 12 months; there was complete resolution of the proteinuria in 11 (69%) of these patients. The level of proteinuria did not predict the presence or absence of important kidney disease. However, if isolated proteinuria persists for more than 1 year, it is then unlikely to spontaneously remit and a renal biopsy is indicated to clarify the nature of any underlying glomerulopathy. In children with isolated proteinuria of 1 years duration, there is a high likelihood of detecting significant renal pathology that may adversely affect their long-term prognosis.

Hypercalciuria in children with renal glycosuria: evidence of dual renal tubular reabsorptive defects.

During the past 5 years, we have identified idiopathic hypercalciuria in five of seven patients referred for evaluation of renal glycosuria between 1985 and 1991. The children, all boys, ranged in age from 6 to 12 years. Endocrine function was normal, and none of the patients had hyperparathyroidism, hypercalcemia, renal tubular acidosis, or other secondary causes of hypercalciuria. The calcium/creatinine ratio in a fasting urine specimen was elevated in all five children who had hypercalciuria, with a mean value (+/- SD) of 0.34 +/- 0.06 (normal, < 0.2). In one child who had renal colic with spontaneous passage of gravel-like material, the idiopathic hypercalciuria persisted after 1 week on a diet containing 2000 mg of sodium and 300 mg of calcium. On the basis of studies that examined the site along the nephron responsible for hypercalciuria in rats with streptozocin-induced diabetes, we speculate that in children with renal glycosuria, there is defective reabsorption of glucose and calcium in the straight portion of the proximal tubule or in the collecting duct. It is likely that a similar mechanism accounts for the idiopathic hypercalciuria in children with diabetes mellitus.

Inadequacy of captopril challenge test for diagnosing renovascular hypertension in children and adolescents

A captopril challenge test (CCT) for renovascular disease in adults was described recently. We used it in 20 consecutive, untreated hypertensive children and adolescents. All had a normal urinalysis and glomerular filtration rate and non-diagnostic renal sonograms or intravenous urograms. Plasma renin activity (PRA) was measured before and 1 h after administration of captopril (0.76±0.17 mg/kg). The CCT was positive in 10 patients. Renal arteriograms were performed in 7 patients with a positive CCT and in 2 with a negative CCT. Renovascular disease was found in 4 patients, 1 of whom had a negative CCT. The PRA response to captopril was the same in patients with true- and the false-positive tests. The predictive value of the positive test was 43%. In conclusion, we did not find the CCT, as described for adults, to be of value in children and adolescents.

IgA nephropathy in a child with human immunodeficiency virus type 1 infection

Infection with the human immunodeficiency virus type 1 (HIV-1) can cause a spectrum of renal disease, termed acquired immunodeficiency syndrome (AIDS) nephropathy. The most common clinical manifestations of kidney involvement in HIV-1-infected patients are proteinuria and/or nephrotic syndrome, and the histopathological pattern usually reveals focal segmental glomerulosclerosis. We describe an 8-year-old child with AIDS who presented with recurrent gross hematuria. A kidney biopsy demonstrated IgA nephropathy. This unique case indicates that the range of kidney disease in HIV-infected children may be broader than originally thought, and that these patients warrant a complete evaluation of any renal abnormality.

The renal functional and structural consequences of corticosteroid and angiotensin-converting enzyme inhibitor therapy in chronic puromycin aminonucleoside nephropathy.

Glomerular diseases are characterized by increased urinary protein excretion. Treatment of this abnormality frequently involves administration of corticosteroids and angiotensin-converting enzyme inhibitors. There has been much recent interest in the potential impact of these drugs on progressive renal dysfunction, since they have opposing effects on intraglomerular hemodynamics. Therefore, we investigated the effect of methylprednisolone or captopril treatment on animals with chronic puromycin aminonucleoside nephropathy. In rats given a single injection of puromycin aminonucleoside, 15 mg/100 g body weight, both methylprednisolone and captopril significantly reduced proteinuria at 6 months [83±14 untreated (n=7), 34±6 with methylprednisolone (n=8), and 6±1 mg/24h with captopril (n=5),P<0.001]. Segmental glomerulosclerosis occurred with equal frequency in the untreated (7.8±2.3%) and methylprednisolone-treated rats (5.0±1.11%), but was significantly reduced by the administration of captopril (1.0±0.5%,P<0.001). We conclude that in chronic puromycin aminonucleoside nephropathy, treatment with corticosteroids reduces proteinuria without increasing the incidence of segmental glomerulosclerosis. Therapy with an angiotensin-converting enzyme inhibitor substantially decreases proteinuria and lessens the severity of glomerular scarring.

Acute Interstitial Nephritis Associated with IgA Nephropathy in Children.

Abstract. 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.