Leonard G. Feld

Chronic renal insufficiency in children and adolescents: The 1996 annual report of NAPRTCS

Abstract. The 1996 annual report of the Chronic Renal Insufficiency Arm of the North American Pediatric Renal Transplant Cooperative Study (NAPRTCS) summarizes descriptive data and highlights important features on 1,725 patients from 130 centers. This database contains information on patients with an estimated glomerular filtration rate (GFR) ≤75 ml/min per 1.73 m2 as calculated by the Schwartz formula, who were treated on or after 1 January 1994. Thus this report reflects 2 years of data entry. Analysis of the data revealed that nearly two-thirds of patients registered had a structural anomaly. On average, patients were 1.5 standard deviations below age- and sex-specific norms for height, and 0.6 standard deviations below weight norms. Mean serum creatinine for the entire group was 2.4 mg/dl and 68% of patients had a baseline GFR of at least 25 ml/min per 1.73 m2. The mean hematocrit for all children at registration was 33.3±6.3%, and did not vary among age groups. Overall, 30.9% of patients had a hematocrit <30%. Only 12.8% of patients were receving Epoetin therapy. Although still in infancy, the Chronic Renal Insufficiency Arm of the NAPRTCS database in providing important insights into this disorder.

Laboratory Predictors of Fluid Deficit in Acutely Dehydrated Children

To determine which laboratory studies are most predictive of the fluid deficit in acutely dehydrated children, we studied a convenience sample of 40 children requiring intravenous fluid resuscitation. Nine laboratory studies (serum BUN/cr, total serum C02, serum uric acid, serum anion gap, urine anion gap, venous pH, venous base deficit, urine specific gravity, and fractional excretion of sodium) were individually assessed in simple linear regression models with fluid deficit as the dependent variable. Only the serum BUN/cr and serum uric acid were significantly associated with increasing fluid deficit (r=0.52, P=0.0005 and r=0.35, P=0.03, respectively). The sensitivities and specificities of these two laboratory studies for the detection of >5% fluid deficit were poor. Conventional laboratory studies used to assess dehydration in children are poorly predictive of fluid deficits.

Limited Evaluation of Microscopic Hematuria in Pediatrics

Objective. The purpose was to determine the value of the standard laboratory and radiologic evaluation of microscopic hematuria in children, and to determine the prevalence of idiopathic hypercalciuria in those children referred for evaluation of unexplained microscopic hematuria. Methods. This was a retrospective study of 325 children referred from 1985 to 1994 for the evaluation of asymptomatic microscopic hematuria. The diagnostic studies reviewed included serum creatinine, blood urea nitrogen, serum electrolyte studies, serum complement concentration, antinuclear antibody, urinalysis, urine calcium to creatinine ratios, urinary protein to creatinine ratio and/or 24-hour urinary protein excretion, renal ultrasounds, intravenous pyelograms, voiding cystourethrograms, and historical information. Results. All creatinine and electrolyte values were normal for age, and none of the biochemical tests obtained in the children with hypercalciuria was abnormal. Of the 325 patients with idiopathic microscopic hematuria, only 18 had abnormal renal ultrasound examinations and 9 voiding cystourethrograms showed low-grade reflux. Hypercalciuria was found in 29 patients. The family history was positive for urolithiasis in 16% of patients without hypercalciuria compared with 14% of patients with hypercalciuria. A positive family history of hematuria was reported in 25% of patients; 62 patients did not have hypercalciuria and 4 of the patients had hypercalciuria. Microscopic hematuria in children is a benign finding in the vast majority of children. Conclusions. Our data demonstrate that a renal ultrasound, voiding cystourethrogram, cystoscopy, and renal biopsy are not indicated in the work-up of microscopic hematuria, and microhematuria in the otherwise healthy child is a minimal health threat, rarely indicative of serious illness.

Association of Kawasaki disease and interstitial nephritis

Renal insufficiency is a rare manifestation of Kawasaki disease. We report a 2·5-year-old boy with Kawasaki disease who developed acute renal failure during the acute phase of his illness. A percutaneous renal biopsy revealed acute interstitial nephritis. No etiological agent could be identified and renal recovery occurred with supportive care alone.

Nitric oxide metabolism following unilateral renal ischemia/reperfusion injury in rats

Abstract. Renal ischemia/reperfusion (I/R) injury results in decreased glomerular filtration and renal blood flow (RBF) and increased urine output, characterized by natriuresis and impaired concentrating ability. We studied unilateral I/R in rats to assess renal handling of nitric oxide (NO). Prior to I/R, we measured urine flow rate (V), inulin clearance (CIN), para-aminohippuric acid clearance (CPAH), NO clearance (CNOx determined from metabolites NO2 and NO3), tubular transport of NOx (TNOx, filtered load ± urinary excretion), urine sodium and potassium excretion (UNaV, UKV), fractional excretion of sodium (FENa), and fractional excretion of NOx (FENOx) in each kidney. The left renal artery was then ligated for 30 min, followed by 30 min of reperfusion, and all measurements were repeated. CIN and CPAH were decreased in I/R kidneys compared with the contralateral kidney or pre-ischemia controls. V, FENa, and UKV were all significantly increased in I/R kidneys. Plasma NOx concentration was lower after injury in all animals (23.3±2.8 post injury vs. 30.4±7.7 μM pre injury, P <0.05). CNOx was significantly higher in I/R kidneys (0.14±0.05 ml/min per g kidney weight) than in pre-injury kidneys (0.03±0.02 right, 0.04±0.30 left) or the contralateral controls (0.04±0.02) (P <0.05 for all three controls). TNOx showed net tubular reabsorption of NOx in all kidneys (11±6 in post-ischemic left kidneys vs. 25±20 in left pre-ischemia, 33±13 in right pre-ischemia, and 21±4 right post-ischemia, nM/min per g kidney weight, P = NS). FENOx was higher in injured kidneys (28%±18) than in pre-injury (3%±0.6, 5%±3) or contralateral controls (6%±3) (P <0.05 for all three controls). Renal NOx excretion and clearance are increased despite decreased plasma levels of NO metabolites after I/R injury. This increased excretion is not dependent on RBF or glomerular filtration, but may be related to impaired tubular reabsorption of NOx combined with increased intra-renal NO production.

HEMATURIA : An Integrated Medical and Surgical Approach

The need to perform a detailed work-up of microscopic hematuria is based on the following set of questions: Does the history or physical examination findings suggest systemic or renal disease? Is the patient able to acidify and concentrate urine? Is proteinuria present? Do other family members have hematuria or other renal problems? Does the microscopic analysis show casts, crystals, or WBCs? Are the RBCs eumorphic or dysmorphic? Using this scheme of questions, most children do not require laboratory tests or radiographic studies. In the case of gross or macroscopic hematuria, the initial evaluation may require only a urine culture, urine calcium-to-creatinine ratio, and renal and bladder sonography or a very detailed evaluation for renal parenchymal disease, stones, tumors, or anatomic abnormalities. In these instances, consultation with a pediatric nephrologist, urologist, or both is necessary.

Microalbuminuria in an Adolescent Cohort With Insulin-Dependent Diabetes Mellitus

To document the incidence of microalbuminuria in children and adolescents with longstanding insulin-dependent diabetes mellitus (IDDM) and to compare the clinical characteristics and determinant risk factors of those with and without microalbuminuria, 135 adolescent patients with IDDM for 5 years or longer were evaluated. The study population was divided on the basis of microalbumin excretion into normal (<20 μg/min), incipient (20-200 μg/min), and overt (>200 μg/min) nephropathy groups. There were 106 patients in the normal group, 24 patients in the incipient group, and five in the overt nephropathy group. Glycosylated hemoglobin, cholesterol concentration, and glomerular filtration rate (GFR) were analyzed. The incidence of incipient and overt nephropathy was 17.8% and 3.7%, respectively. Mean cholesterol concentration in the incipient and overt nephropathy groups (208 ± 39 mg/dL [5.4 ± 1.0 mmol/L] ) and 227 ± 49 mg/dL [5.9 ± 1.3 mmol/L] , respectively) was significantly higher than the normal group (186 ± 37 mg/dL [4.8 ± 0.9 mmol/L] P<0.05). Similarly, systolic and diastolic blood pressures were significantly higher in the incipient and overt nephropathy groups compared to the normal group. This study confirms the high incidence of incipient and overt nephropathy in adolescents with IDDM early in the course of the disease.

Seizures During Correction of Hypernatremic Dehydration in an Infant

This 16-day-old breast-fed infant had a three-day history of poor feeding and increasing somnolence. She was the 3.6-kg product of an uncomplicated first pregnancy. Fever, emesis, and diarrhea were denied. Examination revealed a lethargic, emaciated, and severely dehydrated baby who weighed 2.3 kg. Dextrostix blood glucose was 20 mg/dL. Normal saline (15 mL/kg), DsoW (1 mL/kg), and DIO 0.45% saline at 50 mL/h were administered. The infant was transferred to the hospital. On arrival, the baby was afebrile with a pulse of 180 beats per minute and a BP of 45/20 mmHg. Treatment included intravenous volume expansion with -0.9% saline and colloid until vital signs and central venous pressure were normal, followed by D2.5 0.2 % saline plus 50 mEq NaHC03/L at a rate calculated to replace fluid deficits over 48 hours. Eight hours after admission, peritoneal dialysis with a 1.5% dextrose, 160 mEql L sodium solution was initiated because of anuria and progressive azotemia. Four hours later the infant became increasingly lethargic. Generalized seizures developed and recurred over the next 24 hours, despite appropriate anticonvulsant therapy. Computed tomography (CT) of the brain suggested cerebral edema. Pertinent laboratory information is summarized in Table 2. The hypernatremia was corrected after 96 hours. After resolution of the hyperosmolar state, there were no further seizures. Results of repeat neurological examination, EEG, and CT scan of the head were normal before discharge from the hospital.

Nitric Oxide-Inhibitory Effect of Aminoguanidine on Renal Function in Rats

Inhibition of nitric oxide (NO) synthesis by structural analogues of L-arginine reduces glomerular filtration, renal blood flow, sodium excretion, and urine output. N(G)-nitro-L-arginine methyl ester (L-NAME) inhibits constitutive and inducible isoforms of NO synthase, while aminoguanidine (AG) selectively inhibits inducible isoforms of NO synthase. We assessed the NO-inhibitory activity of AG on renal function. Rats were treated with aminoguanidine 50 mg/kg daily for 2 months, followed by L-NAME (25 mg/kg/day) for 1 week to inhibit all NO synthase isoforms. After treatment with L-NAME, we performed baseline renal function measurements, then infused L-arginine (2.5 mg/100 g BW x min) to reverse NO inhibition and assessed whether AG exerted NO-inhibitory activity independently of L-NAME. Prior to L-arginine infusion, AG-treated rats did not differ from controls with respect to body weight, kidney weight, systolic blood pressure, urine flow rate, urinary protein or albumin excretion, or urinary excretion of NO metabolites. After L-arginine infusion, all animals showed a 10-15% decrease in mean arterial blood pressure. L-Arginine-induced increases in urine flow, inulin clearance, PAH clearance, sodium excretion, and NO metabolite excretion were blunted in aminoguanidine-treated animals. To assess long-term effects of aminoguanidine, rats were treated for 12 months. Urinary excretion of NO metabolites was lower than controls. Inulin clearance was higher than controls. Aminoguanidine blunts the effect of L-ariginine on renal hemodynamics independently of the nitric oxide synthase inhibitor, L-NAME. However, the use of aminoguanidine for 12 months in rats did not adversely affect renal function.

Renal biopsy in children with asymptomatic hematuria or proteinuria: survey of pediatric nephrologists

The decision to perform a renal biopsy on children with asymptomatic hematuria or proteinuria remains a problem for clinicians. To assess the current opinion of 349 pediatric nephrologists on this issue, case summaries of a 9-year-old boy with 20 urinary red blood cells per high power field without proteinuria and a 9-year-old boy with 2+ proteinuria (600 mg/day) without hematuria were distributed to each specialist. Seventy-three percent (n=256; 3∶1, male:female) responded. Five percent would biopsy the child with asymptomatic hematuria. The main reasons were academic interest, parental pressure for a diagnosis/prognosis and concern for future economic impact on the child (i.e., life insurance). The determinations to biopsy for hematuria were not related to age or sex of the nephrologist. In contrast, 38% (n=96) of the pediatric nephrologists would perform a biopsy on the child with proteinuria. The major reasons for biopsy were academic interest and potential for drug therapy. With a normal history, physical examination and laboratory/radiographic evaluation, the vast majority of pediatric nephrologists in North America support a conservative approach to the child with asymptomatic hematuria or proteinuria.