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.

Special topics in pediatric hypertension.

This review emphasizes four major areas of pediatric hypertension. Because hypertension is the most common reason student athletes fail the sports pre-participation examinations, we have attempted to provide a rationale approach to the decision process to permit a hypertensive child to partake in leisure and competitive sports. Without question, obesity is a major reason for referral for hypertension to a pediatric nephrologist. The work-up should be directed to diet control and an exercise program to achieve sustained weight reduction. Hypertension associated with chronic renal failure and renal disease secondary to insulin-dependent diabetes mellitus is a major problem in pediatric and adult nephrology. With adequate control of systemic blood pressure, progressive decline in renal function may be delayed. By understanding these common areas of associated pediatric hypertension, a more systematic approach to the evaluation and treatment can be achieved.

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

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 (C[IN]), para-aminohippuric acid clearance (C[PAH]), NO clearance (C[NOx] determined from metabolites NO2 and NO3), tubular transport of NOx (T[NOx], filtered load +/- urinary excretion), urine sodium and potassium excretion (U[Na]V, U[K]V), 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. C(IN) and C(PAH) were decreased in I/R kidneys compared with the contralateral kidney or pre-ischemia controls. V, FENa, and U(K)V 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 microM pre injury, P < 0.05). C(NOx) 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). T(NOx) 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.

Screening dipstick urinalysis: a time to change.

OBJECTIVE: This study attempted to determine the minimal cost of screening dipstick urinalyses in a hypothetical cohort of 2000 asymptomatic pediatric patients in a primary care setting. METHODOLOGY: The minimal cost utilizing a private practitioner in an urban or suburban group pediatric setting was calculated. Costs were determined by using current charges for supplies ordered to perform tests in the office, charges for tests performed by a commercial laboratory, and the cost of an initial evaluation by a pediatric nephrologist. Data from published studies were also utilized. RESULTS: Nine percent (179/2000) of patients were calculated to have an initial abnormal urinalysis. Upon retesting only 1.5% (29/2000) of patients were calculated to have a persistent abnormality. The calculated rate of a false positive/transient abnormality for all patients in the hypothetical cohort of 2000 asymptomatic pediatric patients was 84% (150/179). The calculated minimal cost for the outpatient evaluation of 2000 asymptomatic pediatric patients by dipstick urinalyses ranged between $5022 to $6475. The range depends on whether 50% versus 100% of patients with a repeat abnormal dipstick urinalysis were referred to a pediatric nephrologist for further evaluation. The calculated cost was $1290 to initially screen all 2000 patients with a dipstick urinalysis or 65 cents per patient. The calculated cost to evaluate the 29 patients with any persistent abnormality on repeat dipstick urinalysis was $3732 to $5185 or $129 to $179 per patient. This is the calculated cost for a single screening of 2000 asymptomatic pediatric patients. The calculated cost for four multiple screening urinalyses as currently recommended is $20 088 to $25 900. Additionally, these are only minimal initial calculated costs. Costs of any renal imagining or function studies ordered by the pediatric nephrologist or the pediatrician pursuing a further evaluation on his/her own were not included. CONCLUSION: Multiple screening dipstick urinalyses in asymptomatic pediatric patients are costly and should be discontinued. In their place, we propose that a single screening dipstick urinalysis be obtained at school entry age, between 5 and 6 years old, in all asymptomatic children. The sample should be a first morning void.

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.

Enalapril and renal function in hypertensive rats transgenic for mouse renin gene.

We examined the effect of long-term enalapril treatment on renal function and histology in the monogenetically hypertensive TGR(mRen2)27 rat strain. Untreated transgenic rats had significantly (P<.01) higher blood pressures than treated transgenic and control animals throughout the study. Urinary nitric oxide metabolite excretion was significantly lower in young transgenic rats and rose with enalapril, suggesting abnormal TGR nitric oxide production and its correction by enalapril. Converting enzyme inhibition produced preferential preglomerular vasodilatation and increased renal blood flow (6.5 +/- 0.5 versus 9.0 +/- 0.7 mL/min per gram kidney weight, P<.05) without altering whole-kidney and single-nephron glomerular filtration rates in TGR(mRen2)27. Glomerular capillary pressure fell modestly in treated transgenic animals (54 +/- 1 versus 50 +/- 1 mm Hg, P<.05). These hemodynamic changes were associated with reductions in albuminuria (59 +/- 6 versus 9 +/- 2 mg/d, P<.01) and glomerulosclerosis in TGR. However, urinary albumin excretion (15 +/- 3 versus 3 +/- 1 mg/d, P<.05) and glomerulosclerosis also declined in treated control animals in the absence of significant alterations in glomerular hemodynamics. The mechanism of the beneficial effect of enalapril on the TGR(mRen2)27 kidney is unclear but could involve either control of hypertension or suppression of the intrarenal renin-angiotensin system.

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 CO2, 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.

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 transplantation in children from 1987-1996: the 1996 Annual Report of the North American Pediatric Renal Transplant Cooperative Study.

The 1996 Annual Report of the North American Pediatric Renal Transplant Cooperative Study (NAPRTCS) summarizes data voluntarily collected from 130 centers on 4329 children and adolescent patients who received renal transplants on or after January 1, 1987. This report updates information on transplants; data on dialysis and chronic renal insufficiency have, for the first time, been reported separately (in submission). The NAPRTCS registry shows that the majority of pediatric renal transplants are performed in children above 6 years of age (73%). The most frequent diagnoses include obstructive uropathy (16%), aplastic/hypoplastic/dysplastic kidneys (16%), and focal segmental glomerulosclerosis (12%). Pre-emptive transplantation was performed in 24% of patients. Triple drug maintenance therapy with prednisone, cyclosporine and azathioprine was used by >70% of all transplant recipients throughout 7 years of follow-up. Fifty-six per cent of transplant recipients were rehospitalized during months 1-5 (51% live donor (LD), 62% cadaver donor (CD)), with rejection and infection as the main causes. In the period 30-35 months post-transplant, 19-22% of patients (163 LD, 185 CD) were rehospitalized. The median time to the first rejection was 46 days for CD transplants and 377 days for LD grafts (p<.001). Six-year graft survival rates were 73% and 56% for LD grafts and CD grafts, respectively (p<.001). The overall growth deficit was constant over a period of 60 months. However, children transplanted under 5 years of age reduce their height deficit by about one-third compared to an increase in height deficit of up to 22% for older children. The NAPRTCS data analysis also demonstrates a delay in first rejection episodes in LD compared to CD transplants, and a steady improvement in CD graft survival over the past 5 years in pediatric transplant recipients.

Decreased urinary excretion of nitric oxide in acute rejection episodes in pediatric renal allograft recipients.

Acute renal allograft rejection continues to have a negative effect on graft survival despite a better understanding of the molecular basis of renal allograft rejection. Nitric oxide (NO) has important biological functions in cell defense and injury and some evidence exists that it may act as an immunomodulator in allograft transplantation. To determine if NO has any role in acute renal allograft rejection in pediatric patients, acute rejection episodes in pediatric renal transplant recipients were evaluated. Four out of eleven patients who received a renal allograft in 1995 at Children's Kidney Center at The Children's Hospital of Buffalo had eight episodes of acute rejection. One patient received a living-related and three received cadaveric grafts. Stable metabolites of NO (NO-2 + NO-3 = NOx) were measured in the serum and urine samples of the patients daily. Serum levels of NO did not change significantly during acute rejection episodes. Urinary NOx levels decreased by 73+/-9% of the baseline values during episodes of acute rejection: mean +/-SE urinary nitric oxide/creatinine ratio (NOx/Cr) of 0.17+/-0.05 at baseline vs. 0.05+/-0.01 during rejection (P=0.02). Successful treatment of acute rejection by administration of high dose i.v. steroids or OKT-3 induced acute rises in the urinary NO levels to baseline values: NO/Cr = 0.17+/-0.04 (mean +/-SE). We conclude that urinary NO excretion decreases significantly during acute renal allograft rejection and that NOx concentration in the urine increases in response to successful antirejection therapy.

Nutritional intake in children with renal insufficiency: a report of the growth failure in children with renal diseases study.

OBJECTIVE: This study was designed to assess sequentially the nutrient intake in children with chronic renal insufficiency and its relationship to body size, the level of renal failure, and growth velocity. METHODS: The nutrient intake from 401 4-day food records obtained from 120 children with renal insufficiency over a 6-month observation period was analyzed. The height and weight were measured at the beginning and end of the observation period. The glomerular filtration rate was estimated from the height and serum creatinine. RESULTS: The mean caloric intake in these children was 80 +/- 23% (mean +/- SD) of the Recommended Dietary Allowance (RDA) for age. Fifty-six percent of the food records obtained from these children revealed a caloric intake that was less than 80% of the RDA. Caloric intake expressed as the %RDA for age decreased with increasing age. However, the mean caloric intake when factored by body weight was in the normal range. There was no correlation between caloric intake and height velocity. The mean protein intake in these children was 153 +/- 53% of the RDA. Further, 45% of the food records indicated a protein intake greater than 150% of the RDA. There was no relationship between the degree of renal insufficiency and caloric or protein intake. Calcium, vitamin, and zinc intakes were also low. CONCLUSIONS: Children with chronic renal failure consume less calories than their age matched peers, but the majority of these children appear to ingest adequate amounts for their body mass. This reduction in caloric intake occurs early in renal insufficiency. They also ingest inadequate amounts of calcium, zinc, vitamin B6, and folate.

Hypertensive encephalopathy and reversible magnetic resonance imaging changes in a renal transplant patient.

An 18-year-old renal transplant patient presented with sudden onset of seizures almost 2 years after she received the graft. Diagnostic work-up was unrevealing except for magnetic resonance imaging abnormalities of the brain that resolved spontaneously 4 weeks later. In this brief report, we discuss the etiology of the seizures and neurological abnormalities in renal transplant patients in light of the findings of our patient.

Spectrum of glomerulocystic kidneys: a case report and review of the literature.

An 8-year-old boy developed end-stage renal disease 7 years after the in utero diagnosis of bilateral cystic kidneys. There was no history of cystic renal disease in the family. Initial ultrasonographic screening of the parents failed to reveal cysts in the kidneys. Pathological evaluation of the kidney biopsy findings was consistent with the glomerulocystic kidney disease. He had bilateral nephrectomies in preparation for a living related renal transplant at 7 years of age. At that time, a repeated renal ultrasound examination of the mother showed bilateral cystic kidneys. Pathological evaluation of the nephrectomy specimens confirmed the diagnosis of autosomal dominant polycystic kidney disease. In this report, a discussion of the differential diagnosis of glomerular cysts and the relationship of glomerulocystic kidney disease and autosomal dominant polycystic kidney disease is provided.

Prolonged hypocomplementemia in poststreptococcal acute glomerulonephritis.

Complement levels conventionally return to normal in eight weeks in patients with poststreptococcal acute glomerulonephritis (PSAGN). The objective of this study was to determine the significance of prolonged hypocomplementemia (> 8 weeks) in this group of patients. Between April 1993 and January 1995, 20 patients were followed prospectively for a mean of 6 months (range 3-20 months after the episode of PSAGN. Serum C3 concentrations were measured at diagnosis and at regular intervals. Five patients (26%) had prolonged hypocomplementemia. Percutaneous renal biopsies were performed in three patients which revealed findings consistent with the clinical diagnosis of PSAGN. All of these patients showed gradual improvement of their symptoms; some have persistent microscopic hematuria without proteinuria. Kidney function is normal in all despite hypocomplementemia. We conclude that hypocomplementemia (> 8 weeks) with resolving features of acute glomerulonephritis does not exclude the diagnosis of PSAGN, and a renal biopsy may be deferred if there is clinical improvement.

Sex chromosomes do not influence renal injury in borderline hypertensive rats.

The present study was undertaken to investigate whether the development of proteinuria in the borderline hypertensive rat (BHR) is influenced by the Y chromosome and to determine if the onset of proteinuria in the BHR is delayed when blood pressure is lowered with enalapril, an angiotensin I converting enzyme inhibitor. Male F1, rats were the first-generation offspring of the mating of spontaneously hypertensive (SHR) females and Wistar-Kyoto (WKY) males and the mating of SHR males and WKY females. At 20 weeks of age, enalapril (125 mg/l) was added to the drinking water. Untreated BHR and enalapril-treated BHR (BHRE) were followed to 90-100 weeks of age. Urine was collected every 10-20 weeks for determination of protein, albumin, and nitric oxide (NO2/NO3) metabolite excretion. Indirect blood pressure in BHR from both crosses was approximately 175 mm Hg from 20 to 90-100 weeks of age. Enalapril lowered blood pressure by about 30 mm Hg, but was ineffective in reducing urinary protein or albumin excretion rates at any age. Urinary excretion of nitric oxide metabolites was similar in all groups at all time periods. There were significant differences in the percent of glomerulosclerosis between the two matings. Based on these results, renal injury in the BHR is not associated with the Y chromosome and can be dissociated from hypertension. Further studies using congenic and transgenic technology will be necessary to identify functions of genes and associations with hypertension in order to understand the kidney disease in this model of hypertension.

Resistance to glomerular injury in the diabetic biobreeding rat.

This study was designed to determine whether the diabetic BioBreeding rat develops significant renal injury following long-term moderate to severe hyperglycaemia. Diabetic and control rats were followed from the onset of diabetes (2-4 months) to 18 months of age. Frank proteinuria and/or albuminuria were always absent. Glomerular filtration rate, measured by inulin clearance (ml min-1 (100 g body weight)-1), was significantly higher in diabetic rats than in controls at 10, 12 and 18 months of age. Advanced glycosylation end-product cross-links assessed by percentage solubility of tail tendon collagen were moderately increased in diabetic compared with control animals. Urinary excretion of advanced glycosylation end-products in unfractionated urine and in urine fractionated for low molecular mass peptides (< 10 kDa) was 11-fold greater in the diabetic rats than in the control group. Urinary excretion of nitric oxide metabolites (nmol NO2- and NO3- (24 h)-1) were significantly (P < 0.05) greater in diabetic rats than in controls after 8 months of age. Mild histopathology resembling human diabetic nephropathy, including increased mesangial volume and glomerular basement membrane thickness, was detected at 18 months of age. The findings of hyperfiltration and mild glomerular morphological changes in diabetic BioBreeding rats are similar to the abnormalities seen in stage 2 human diabetic nephropathy. We hypothesize that two factors which may contribute to the resistance or tolerance to renal injury in the BioBreeding diabetic rat are increased nitric oxide production and the decreased accumulation of advanced glycosylation end-products.