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This educational review will highlight the historical and contemporary references that establish a basic understanding of measurements of kidney function in the neonate and its relevance for the life of an individual. Importantly, the differential renal function of preterm infants relative to term infants has become paramount with the increased viability of preterm infants and the realization that kidney function is associated with gestational age. Moreover, neonatal kidney function is primarily associated with absolute renal mass and hemodynamic stability. Neonatal kidney function and its early developmental progression predict lifelong cardiovascular and renal disease risks. Validation of estimation equations of kidney function in this population has provided important reference data for other investigations and a clinical basis for prospective and longitudinal follow-up. Future research should be directed towards a better understanding of surrogate markers of kidney function from infancy through adulthood. Pediatric nephrologists should be aware of the developmental aspects of kidney function including the importance of the congenital nephron endowment and the preservation of kidney function throughout a lifetime. • Nephrogenesis occurs in utero in concert with other organ systems by branching morphogenesis, including the lungs, pancreas, and vascular tree, with over 60 % of nephrons being formed during the last trimester. • Infants born preterm before 36 weeks' gestation are in active nephrogenesis and are at increased risk of having a decreased nephron endowment from prenatal and postnatal genetic and epigenetic hazards that will impact the patient for a lifetime. • Post-natal adaptation of kidney function is directly proportional to the number of perfused nephrons, estimated by total kidney volume (TKV), mean arterial pressure (MAP), and gestational age. • Accurate measurement of glomerular filtration rate (GFR) in infants is problematic due to the unavailability of the gold standard inulin. The traditional use of creatinine to estimate GFR is unreliable in preterm infants due to its tubular reabsorption by immature kidneys and its dependence on muscle mass as an endogenous marker. Alternative endogenous markers to estimate GFR are cystatin C and beta trace protein (BTP). • Long-term follow-up of renal function in those born preterm should be life long and should include assessment of GFR, total kidney volume (TKV) relative to body surface area (BSA), and cardiovascular risks including hypertension and vascular stiffness.

Recurrence of focal glomerulosclerosis (FSGS) following renal transplantation is a common cause of allograft loss and clinical morbidity. Recent attempts to control proteinuria and morbidity with plasmapheresis (PP) have met with limited success. Our experience with the use of mycophenolate mofetil (MMF) and angiotensin blockade (AB) in the management of refractory FSGS pre transplant suggested its potential benefit in post-transplant recurrence. This report presents our 25-year experience in pediatric renal transplantation of patients with FSGS divided into two treatment eras: Era 1-prior to use of daclizumab (anti-IL-2R) and Era 2-after daclizumab. A total of 179 pediatric patients were transplanted during the 25-year period. FSGS was confirmed in 27 (15%); 16 of 28 allografts (57%) had recurrence of FSGS during the post-transplant period. In Era 1, only 6 of 16 (38%) recurred in the allograft, while 10 of 12 (83%) recurred during Era 2. The odds ratio of recurrence of FSGS in the allograft after induction with anti-IL-2R was 8.3 (95% confidence interval=1.3-52, P =0.02). Only 2 patients in Era 1 received PP, while 10 in Era 2 were entered into an intensive PP protocol followed by maintenance with AB consisting of angiotensin receptor blockers alone, or in combination with angiotensin-converting enzyme inhibitor. Although proteinuria decreased an average of 80+/-16% with PP, the response was variable and severe morbid edema persisted in poor responders. Maximum benefit occurred with the addition of AB and MMF. After a follow-up of 27+/-15 months, proteinuria has shown a sustained decrease of 94+/-8% below baseline. In conclusion, our experience suggests that, with recurrent FSGS, a limited course of PP followed by maintenance therapy with AB and MMF improves symptoms and may preserve allograft function.

Children with end-stage renal disease (ESRD) often remain hypertensive despite bilateral nephrectomy and aggressive fluid removal on hemodialysis. We speculated that an extrarenal source of renin might contribute to the release of "tissular" angiotensin-II (AT-II) generating hypertension in anephric patients. At the same time, experimental evidence supports that peripheral AT-II vasoconstrictive effect is likely mediated by endothelin-1 (ET-1). Thus, it is conceivable that hypertension in ESRD patients may be due, in part, to a cascade involving vascular production and secretion of AT-II and ET-1. In order to establish the relationship between AT-II, ET-1, and blood pressure we performed a pilot study to measure predialysis systolic and diastolic blood pressures (SBP and DBP, respectively) and serum AT-II and ET-1 levels in 12 anephric children receiving hemodialysis. Predialysis AT-II and ET-1 levels were similar in all patients, and neither value correlated with their mean SBP or DBP. In patients with postdialysis hypertension, there was no correlation between predialysis AT-II and ET-1 plasma levels. We therefore find no evidence to suggest that vascular-mediated AT-II and/or ET-1 contributes significantly to hypertension in anephric patients.

The evaluation and management of children with HIV nephropathy provide a great challenge to the pediatric nephrologist caring for patients with this tragic illness, of which the nephropathy is only part of their problem and extends beyond the patient to the family and all of the supportive team involved. Care decisions should be based on a multi-disciplinary approach in which the infectious disease component is included. There are many areas that require a better understanding, particularly the pathogenesis of HIV nephropathy and the approach to treatment of the nephropathy with specific drugs. Early identification of children affected with this condition and an aggressive approach to management seem essential to the improvement of the outcome of these patients.

Infants born with congenital renal insufficiency generally grow poorly during the first years of life and incur a height deficit that is rarely regained. Actual energy and protein requirements have not been determined for these children. In 12 infants with creatinine clearances less than 70 ml/min per 1.73 m2, growth and nutrient intakes were monitored during the first 2 years of life. Forced feeding regimens after 3 months of age, including gastrostomy in 3 patients, were necessary to maintain energy intakes near 100% of the recommended dietary allowance (RDA). Protein intakes averaged in excess of 140% RDA. Linear growth did not correlate with either energy or protein intakes, suggesting that neither was a limiting factor to growth. Length velocity standard deviation score (LV-SDS) did not correlate with degree of renal insufficiency at any age, but average LV-SDS did relate significantly and inversely to C-terminal parathyroid hormone (PTH) levels. Growth parameters, including LV-SDS and weight velocity SDS (WV-SDS) were lowest at 6 months of age. Weight and length SDS followed with a maximum decline at 12 months of age. While weight for length SDS remained normal and WV-SDS showed recovery during the 2nd year, LV-SDS remained negative. Length SDS stabilized near--2 SDS. In summary, these data suggest that the major height deficit in infants with renal insufficiency is incurred during the first 6 months of life. Ponderal indices suggested that very early nutritional deficits may have been a primary contributor to subsequent height deficits.(ABSTRACT TRUNCATED AT 250 WORDS)

Varying components of the syndrome of human immunodeficiency virus nephropathy (HIVN) have been described, the most pertinent including proteinuria/nephrotic syndrome, progressive azotemia, normal blood pressure, enlarged and hyperechoic kidneys, rapid progression to end-stage renal disease (ESRD), and no response to treatment regimens. The diagnosis of HIVN requires identification of excessive proteinuria or albuminuria, determined by a total protein excretion on a timed urine collection or a high protein/creatinine ratio in a random specimen. Various pathological lesions have been found in HIVN. The lesion of focal and segmental sclerosis (FS/FSS) is most characteristic in adults and usually is associated with a rapid demise. FS/FSS also has been described in approximately one-half of the pediatric patients reported in the literature (31/64). Despite progression to ESRD, the clinical course in children with HIVN is less fulminant than in adults. Other reported histological findings include primarily mesangial hyperplasia as well as minimal change, focal necrotizing glomerulonephritis or lupus nephritis, and hemolytic uremic syndrome. In addition to glomerular pathology, interstitial findings of dilated tubules filled with a unique proteinaceous material, atrophied tubular epithelium, and interstitial cell infiltration are very common. On electron microscopy, most investigators have found tubuloreticular inclusion bodies in endothelial cells of glomerular capillaries. Treatment of patients who develop ESRD remains highly controversial. Most adult patients treated with hemodialysis have succumbed rapidly; peritoneal dialysis has been better tolerated. Transplantation in patients with HIV infection must be considered to be tentative, with reports of acceleration towards full blown acquired immunodeficiency syndrome in some and uneventful 5-year survival in others. The situation of the pediatric patient with HIVN remains unclear and awaits the benefit of experience.

Current clinical requirements mandate the existence of a renal diuretic protocol, which is fast and easy, applicable in all ages and for all indications, convenient for both the patient and the technologist, and provides diagnostic as well as prognostic information. Seventeen years ago a 25-minute protocol, after oral hydration, with no bladder catheterization, and simultaneous injection of mercapto-acetyl-triglycine (MAG(3)) and furosemide (MAG(3)-F(0)), was initiated. It initially was used for the evaluation of drainage and emerged as a protocol to also evaluate the renal parenchyma. Results of this protocol have been published individually, per clinical application. MAG(3)-F(0) was instrumental in the evaluation and prognosis of congenital disorders. For obstruction, in the newborn, an increasing renogram mandates intervention, whereas a downsloping one predicts spontaneous resolution. In children or adults, preoperatively or postoperatively, when the cortex was visualized and drained normally, there was no obstruction, even if urine was retained within a dilated collecting system or an extrarenal pelvis. For diseases of the renal parenchyma, the protocol enabled the diagnosis of acute pyelonephritis (APN) revealing the "regional parenchymal dysfunction," diagnostic of APN. Diffuse parenchymal diseases were characterized by increased residual cortical activity (RCA), and their progression was manifested as a deterioration of RCA. End-stage renal disease was characterized by lack of accumulation and retention. Trauma and leaks were identified with specific patterns. In renovascular hypertension (RVH), an increase in RCA after angiotension-converting enzyme inhibitors is diagnostic of RVH and prognostic of the beneficial effect of angioplasty on hypertension. In renal colic, stratification was possible into (1) complete or severe obstruction requiring immediate intervention, (2) mild obstruction allowing waiting, (3) spontaneous decompression (stunned kidney), and (4) no recent obstruction. In transplants, it enabled differentiation of acute tubular necrosis, acute or chronic rejection and nephrotoxicity, and identified infarcts, RVH, leaks and obstruction. Finally, this method allows for a quick semiquantification of renal function. The clinical usefulness of the MAG(3)-F(0) protocol in most congenital or acquired renal problems is proven through long-term clinical experience and has resulted in a substantial utilization of the test at our Center.

We examined the relative feasibility of using random urinary dipstick testing and urinary protein/creatinine ratios in the quantitation of proteinuria. Sixty-four children with relapsing nephrotic syndrome, ranging in age from 1 1/2 to 16 years, contributed 145 timed urine collections and 150 random specimens, which were analyzed by urinary protein dipstick, quantitation of protein and creatinine, or both. Total protein excretion was expressed as grams per surface area per day and the urinary protein/creatinine ratio as milligrams of protein per milligram of creatinine. Degrees of proteinuria were designated as physiologic (less than 0.1 gm/m2/day), intermediate (greater than 0.1 and less than 1.0 gm/m2/day), or nephrotic (greater than 1.0 gm/m2/day). The log regression analysis of the 24-hour urinary protein/creatinine ratio (y) and total protein excretion (x) was highly significant (r = 0.97; p less than 0.001). The upper and lower confidence limits of the urinary protein/creatinine ratio (1.0 and 0.1, respectively) closely approximated the designations for nephrotic and physiologic proteinuria, respectively. These values were therefore used to classify degrees of proteinuria by the urine protein/creatinine ratio. The validity of these tests was assessed by sensitivity, specificity, and predictive value, and compared with that of random testing by urinary dipstick. The urinary protein/creatinine ratio offered good reliability as a test for classifying degrees of proteinuria and accurately predicting nephrotic and physiologic proteinuria. The random dipstick testing was reliable only when results were distinctly positive and when sensitivity and specificity were low. The error in the total protein excretion value that was imposed by collection errors with high and low variations in the creatinine value (57% of samples) was largely corrected by normalization of the data by log transformation. When controlled for creatinine excretion, linear regression analysis allowed calculation of total protein excretion (TP) from the urinary protein/creatinine ratio (U P/Cr) by the following equation: TP (gm/m2/day) = 0.63 (U P/Cr) at all levels of proteinuria. The random urinary protein/creatinine ratio appeared to offer the most sensitive test for classification of proteinuria in children with nephrosis, with the advantages of ease and expediency not afforded by the 24-hour urine quantitation.

Secondary hyperparathyroidism (SHPT) remains a treatment dilemma in pediatric dialysis patients. Recent experience with paricalcitol (P), a vitamin D analogue, in adults with SHPT has shown equal efficacy and improved survival compared to traditional treatment with calcitriol (C). We present our experience with (C) compared to (P) treatment in our pediatric dialysis patients with SHPT. Twenty-one patients (mean age 11.5+/-5 years) with SHPT (intact parathyroid hormone (iPTH) averaging 1,228+/-496 pg/ml) were studied. Seventeen received (C) followed by (P); while an additional four were treated with either (C=1) or (P=3) alone. After 26+/-8 weeks, average percent (%) decrease in iPTH was similar with (C) and (P) (-60.4+/-34% versus -65.4+/-28%, respectively; p=0.6). In the (P) group, the effective dose in children was greater than in adult trials based on kilogram weight. Episodes of hypercalcemia between the treatment groups were not different. However, episodes of elevated calcium x phosphorus product (CaxP)or =70 mg(2)/dl(2) occurred more frequently in the (C) group (odds ratio=1.5; p=0.01). Paricalcitol appears to be safe and effective in pediatric patients. Data suggest that dosing should be gauged according to degree of SHPT. This should serve as impetus for future pharmacokinetic studies in pediatric dialysis patients.

Steroid-resistant nephrotic syndrome of childhood poses a dilemma in attempting to balance toxicity of medications against long-term prognosis. This report presents our preliminary experience with the novel use of combined mycophenolate mofetil (MMF) and angiotensin blockade (AB) in the treatment of nine children and young adults with focal glomerulosclerosis (FSGS). All patients were steroid resistant and had failed conventional treatment regimens. Prior to the initiation of the MMF-AB protocol, the patients were pre-treated with weekly intravenous methylprednisolone (MP) (15 mg/kg per week) for 4-8 weeks. Angiotensin-converting-enzyme inhibitors and/or angiotensin receptor blockers were begun when intravascular volume was restored. MMF was given at a dose of 250-500 mg/m(2) per day. Proteinuria, as measured by urine protein/creatinine ratios (Up/c), decreased by 43% following MP ( P0.05). After 6 months of MMF-AB protocol, the Up/c was 72% below baseline ( P0.01). This level was maintained for a minimum of 24 months of observation. Similarly, hyperlipidemia, as measured by total cholesterol and triglycerides, improved significantly with treatment (536+/-163 to 265+/-70 mg/dl, 447+/-168 to 230+/-92 mg/dl, respectively, P0.01). Our data support the use of MMF and AB for treatment of steroid-resistant FSGS when other conventional treatments have failed and/or induced toxicity.

Angiotensin converting enzyme (ACE) inhibition scintirenography was performed to help establish the diagnosis and plan treatment of renovascular hypertension (RVH) in 57 hypertensive pediatric patients, 33 infants and 24 children older than 1 year. In 16 of 33 hypertensive infants, ACE inhibition scintirenography established the diagnosis of RVH from renal ischemia (due to aortic or renal arterial thrombi). Two scintigraphic criteria were used for the diagnosis of RVH: criterion I, ischemic and damaged kidney (a non-functioning kidney on or off ACE inhibition) and criterion II, ischemic but not damaged kidney (ACE inhibition induced deterioration of function of the kidney). When criterion I was present and the contralateral kidney was normal, ACE inhibitors could be used for treatment of hypertension without deterioration of renal function; kidneys satisfying criterion I eventually involuted or manifested growth arrest and frequently caused persistent RVH, even after resolution of the thrombus, requiring nephrectomy. When criterion II was present bilaterally, or it was associated with criterion I contralaterally, the use of antihypertensive drugs other than ACE inhibitors was necessary in order to prevent renal insufficiency or failure from ACE inhibitors. However, kidneys with criterion II showed normal growth and, following retraction or dissolution of the aortic thrombus, hypertension resolved. In 2 of 24 hypertensive children older than 1 year, the test was diagnostic of branch renal artery stenosis; RVH was cured by selective angioplasty. ACE inhibition scintirenography is useful in the evaluation and planning of treatment in children with hypertension and may predict the outcome of therapy and ultimate renal function.

Central venous catheters are being increasingly used as hemodialysis vascular access. We evaluated catheter survival, outcome predictors, and complications in a total of 36 catheters used in 13 children and young adults undergoing chronic maintenance hemodialysis through catheter for a duration of 10.4+/-5.6 months. Reasons for catheter failure were: thrombosis 12 of 36 (33%), infection 6 of 36 (17%), and extrusion 2 of 36 (5.4%). Catheters were lost to infection and thrombosis at 1.1 and 2.2 episodes per 1,000 catheter days, respectively. Symptomatic infections, Gram-negative and polymicrobial sepsis increased the risk of catheter failure. Most of the thrombotic episodes occurred in patients with inherent thrombotic tendency. The survival of the 36 catheters was 62% at 1 year. The survival of 13 randomly chosen catheters, 1 from each patient, was 85% at 1 year. The time from insertion to first complication correlated significantly with the outcome (P0.03). We conclude that central venous catheters are still associated with a high rate of failure and may be a regular access choice only in a selected patient population with no inherent thrombotic tendency and no other option available for long-term hemodialysis.

Accurate assessment of proteinuria in pediatric patients infected with the human immunodeficiency virus (HIV) is limited by constraints imposed by timed urine collections and low creatinine excretion in very ill patients with low muscle mass. We therefore sought to validate the use of random urine specimens to quantitate total protein and creatinine excretion in a population of 236 HIV-positive children. A mathematical derivation for estimating urine volume (V) was constructed. The accuracy of the final calculation [V = 832 (kL/Ucr)BSA] (where k = constant, L body length, UCr urine creatinine and BSA body surface area) was tested by regression analysis comparing the calculated and measured volume of 31 urines from ambulatory HIV-negative patients. The correlation coefficient was highly significant (r = 0.77, Por = 0.0001). The relationship was also applied to 23 timed urine specimens from HIV-positive patients with similar significance (r = 0.87, P0.0001). A regression analysis of measured proteinuria against the urine protein: creatinine ratio (Upr/Ucr) in these same urines from the HIV-positive patients yielded a significant relationship both in the linear (r = 0.95, y = 0.4x) and the logarithmic regression (r = 0.97, y = x + 0.4). These data support the use of random Upr/Ucr ratios to estimate daily proteinuria in HIV-infected pediatric patients despite low creatinine excretion rates. The previously accepted values continue to apply, with Upr/Ucror = 2.0 considered normal and2.0 representative of nephrotic proteinuria.

The Growth Failure in Children With Renal Diseases Study was organized to evaluate linear growth in children with chronic; moderate renal failure who are being treated with 1,25-dihydroxyvitamin D 3 or di.hydrotachysterol in a randomized, double-blind, controlled clinical trial. This study was also prompted in 1980 by the need to compare the results (efficacy and safety) of long-term 1,25-dihydroxyvitamin D3 therapy with those in a control group of children with chronic moderate renal failure, with particular attention given to the rate of progression of renal failure, to confirm or refute reports that this therapy may accelerate deterioration of renal function.

Of 155 children with the acquired immunodeficiency syndrome (AIDS) whom we evaluated during a 6 1/2-year period, 12 were found to have proteinuria. Histologic studies of tissue from these 12 patients revealed a wide spectrum of renal disease: focal glomerulosclerosis in 5, mesangial hyperplasia in 5, segmental necrotizing glomerulonephritis in 1, and minimal change disease in 1. In addition, 6 had tubulointerstitial infiltrates, and 10 had glomerular dense deposits. All 10 renal specimens studied by electron microscopy contained endothelial tubuloreticular inclusions. The mean age (+/- SD) of the five patients with focal glomerulosclerosis when this condition was identified was 27 +/- 19 months. All five had severe renal failure within a year and died of other causes during the following year. The mean age of the five patients with mesangial hyperplasia was 38 +/- 31 months. Although none of them went on to have renal failure, four died within 8 +/- 7 months. Ten of the 12 patients with proteinuria died during the study period. Of the two surviving, one had mesangial hyperplasia and the other had minimal change disease. We conclude that children who acquire human immunodeficiency virus (HIV) infection during the perinatal period may have renal disease, most often focal glomerulosclerosis, as is the case in adults, or mesangial hyperplasia. Although 5 of the 12 children we studied had renal failure during the study period, none died of it. Further studies are needed to determine the correlations between clinical and pathological features and the pathophysiology of AIDS nephropathy in children.

The purpose of this study was to determine the acute effects of albumin infusion on blood volume and renal function in preterm infants with RDS and low total serum protein values. Ten infants (gestational age 28 to 36 weeks, body weight 0.88 to 2.46 kg) were given albumin 1 gm/kg (as 25% iv solution) over a ten-minute period. Within ten minutes after infusion was completed, total serum protein concentration, colloid osmotic pressure, and blood volume rose significantly while hematocrit fell from their preinfusion levels (P < 0.0005). Mean arterial blood pressure showed a smaller and less clear-cut increase (P < 0.05). Creatinine clearance rose significantly with infusion; even though preinfusion clearances correlated poorly with gestational age (r = 0.43), postinfusion clearances correlated well (r = 0.92). No significant rises in urinary flow rate Uosm/Posm, or free-water clearance were observed. These results indicate that albumin infusion acutely increases both blood volume and glomerular filtration in premature infants with RDS.

A retrospective analysis of 15 renal transplant patients with end-stage renal disease (ESRD) secondary to systemic lupus erythematosus (SLE) was performed. Overall actuarial patient and graft survival at 6 years was 93 and 84%, respectively. Recipients of HLA-identical kidneys did not appear to be at increased risk of allograft failure due to rejection or recurrent disease. Two biopsy-proven cases of recurrent lupus involving the allograft were observed and are discussed. Those patients currently experiencing excellent graft function (creatinine less than 2 mg/dl) had a significantly longer pretransplantation dialytic interval than the group whose most recent serum creatinine exceeds 2 mg/dl (or returned to dialysis). Posttransplantation monitoring of antinuclear antibody, antidouble-stranded DNA, C3, C4, and circulating immune complexes was not predictive of renal or extrarenal disease activity. Renal transplantation should be considered an excellent therapeutic modality for the lupus patient with ESRD, although an interim period on dialysis of at least 1 year seems warranted.

Sensitivity to cow's whole milk investigated in six patients with the idiopathic nephrotic and an elemental diet was given. After proteinuria had decreased to less than or equal to 500 mg/24 hours on consecutive days patients were challenged with cow's milk. This resulted in the return of significant proteinuria, oedema, and decreased urine volume together with a decrease in serum-IgG concentrations in four patients. Acute alteration of plasma C3 complement component accompanied milk challenge in all 6 patients. There were no consistent alterations in other immunoglobulin concentrations. Intradermal skin testing with cow's milk extract was positive in all patients. These results suggest that in some individuals clinical and biochemical manifestations of the nephrotic syndrome of childhood may be related to hypersensitivity of food products.

Some patients with minimal change nephrotic syndrome (MCNS) present on biopsy mesangial IgM deposits, which may be associated with mesangial hyperplasia. These patients have been considered as a possible subset with a different response to therapy as well as prognosis and designated as mesangial IgM nephropathy or mesangial proliferative glomerulonephritis. However, the clinical relevance of these biopsy findings has been questioned by others. We reviewed the clinical, biopsy, and follow-up data in 61 MCNS children, 33 with mesangial IgM and 28 free of immunoglobulins. There were no significant differences in response to therapy or prognosis between these two groups. The lack of IgM elution and heterologous in vitro C3 fixation in the biopsies of some MCNS cases with IgM mesangial deposits does not support the possibility that the deposited IgM plays an immunologic role.

Peritoneal fluxes of minerals and bone-modulating hormones and their impact on corresponding serum levels and bone mineralization in 7 children on continuous ambulatory peritoneal dialysis (CAPD) were studied. Most mass transfer studies revealed modest losses of calcium into peritoneal effluents. Peritoneal losses of phosphorus and magnesium, although substantial, were not sufficient to normalize hyperphosphatemia and hypermagnesemia in most patients. Parathormone and vitamin D metabolites (25-hydroxyvitamin D and 1,25-dihydroxyvitamin D) were readily detectable in peritoneal effluents. Improved bone mineral content, by sequential densitometries, was associated with amelioration of hyperparathyroidism. These data suggest that CAPD in children induces an overall improvement of disturbed mineral metabolism; nevertheless, peritoneal losses of calcium and vitamin D metabolites must be considered and replenished appropriately.

The clinical application of blood replacement solutions is discussed. It is pointed out that under hemorrhagic shock conditions blood restores renal oxygenation but drugs may make tissue conditions worse. The need for blood replacement solutions is emphasized and their possible use in emergencies and organ preservation is explored. It is concluded that application of modern techniques to the assessment of tissue metabolic conditions may help in identifying the most physiological solutions to replace blood.

We investigated the severity and duration of hyperlipidemia in 59 nephrotic children during relapse and remission. Serum total cholesterol and triglyceride values were greater than or equal to 95th percentile for age and sex in all patients with minimal change nephrotic syndrome in relapse and in patients with non-MCNS and persistent proteinuria. Most of these patients also had a significant elevation of low- and very-low-density lipoproteins. A significant number of children with MCNS during prolonged remission had elevated serum concentrations of total cholesterol (46%), triglycerides (42%), LDL (29%), and VLDL (40%). Persistence and severity of lipid changes correlated well with duration of disease and frequency of relapses. Significantly decreased HDL and HDL/LDL were found in patients with non-MCNS and persistent proteinuria. Our results suggest that nephrotic children may have prolonged periods of hyperlipidemia even after clinical remission. In addition, some of these children with significantly decreased HDL/LDL may be at increased risk of developing premature atherosclerosis.

Aluminium toxicity occurred in two infants with congenital uraemia who had never received phosphate binders or other aluminium-containing agents or intravenous fluids. One patient was treated by peritoneal dialysis from the age of two weeks and died at three months after the sudden onset of neurological symptoms; the other died after one month of conservative management without dialysis. Brain aluminium concentration was high in both infants (6.4 and 47 micrograms/g, respectively) whereas bone aluminium content was normal and there were no histological changes or stainable aluminium on bone biopsy specimens. Both infants were fed with 'Similac PM 60/40'. To investigate possible sources of aluminium, powdered milk formula, sterilised water used for preparation of the feed, and dialysate concentrate (first patient) were analysed. Aluminium concentration was high (232 +/- 60 ng/ml) in powdered milk but negligible in sterilised water and dialysate concentrate (4 ng/ml and 3.4 +/- 2.4 ng/ml, respectively). These findings indicate that proprietary infant milk formula is another source of aluminium. Aluminium-free milk should contribute to the prevention of aluminium toxicity in infants with renal failure.

• Pancreatitis developed in a 12-year-old girl with a one-year history of systemic lupus erythematosus. The pancreatitis was first manifested by panniculitis of the lower extremities. Calcinosis cutis subsequently developed, both in areas of panniculitis and in areas free of panniculitis. The patient's medications at the time of onset of pancreatitis included prednisone, hydrochlorothiazide, and azathioprine, all of which have been reported to be causes of pancreatitis. We wish to alert physicians that pancreatitis associated with cutaneous panniculitis and calcinosis cutis may develop in children with systemic lupus erythematosus. (Arch Dermatol1983;119:491-494)

Baseline and single-dose captopril scintigraphy with 1 mCi of 99mTc-diethylene-triamine-pentaacetic acid (or 99mTc-glucoheptonate) was performed in 5 neonates with renovascular hypertension. Unilateral renal artery thrombosis and/or renal infarction was associated with severe impairment or lack of function on both studies (3 patients). Renal ischemia due to aortic thrombus manifested itself as lack of function only following captopril (2 patients). This approach predicted renal failure as a side effect of captopril therapy in 2 patients, 1 with unilateral (contralateral kidney infarcted) and the other with bilateral renal ischemia from aortic thrombus. Single-dose captopril scintigraphy may be a useful tool to predict tolerance to captopril therapy.

Although abnormalities of calcium and vitamin D metabolism are recognized in children with nephrotic syndrome, longitudinal observations are not available in these patients during periods of relapse and remission. We report observations in 58 children (mean age 10.1 years) with nephrotic syndrome and normal glomerular filtration rate. Hypocalcemia, modest hyperparathyroidism, and strikingly low calcidiol levels were identified during episodes of relapse. Most alterations were transient, and normalized on remission. The plasma concentration of calcitriol, the most active metabolite of vitamin D, was found to be normal in both relapse and remission. In the presence of hypocalcemia and hyperparathyroidism, however, normal plasma calcitriol levels in relapse may be inappropriately low and reflect a state of relative deficiency. Concurrent glucocorticold therapy did not modify the results. A corollary of our observations is that children with relapsing or protracted nephrotic syndrome are at risk of developing metabolic bone disease, even without impairment of glomerular filtration rate.

• Takayasu's disease is a nonspecific arteritis of unknown cause with predilection for the aortic arch and its branches; approximately 20% of those affected are children or adolescents, predominantly females. The purpose of this article is to report the case of a young girl in which the mode of presentation was microscopic hematuria and proteinuria. Subsequently, aortic valvular insufficiency developed and there was evidence of aortitis in the thoracic and abdominal aorta, as well as in the arch. All functional and anatomical cardiac derangements were documented by ultrasound and angiocardiography. Renal biopsies showed progressive glomerular involvement characterized by focal and segmental glomerulonephritis. It is postulated that a common immunologic mechanism was responsible for the aortic and glomerular lesions. ( Am J Dis Child 132:1009-1013, 1978)

Nitroprusside was used with intermittent hemodialysis over a 26-day period in a 6-year-old boy with intractable hypertension. Hemodialysis effectively removed thiocyanate from the blood, thus preventing its accumulation and subsequent toxic manifestations. Prolonged nitroprusside infusion maintained arterial blood pressure at acceptable levels until the patient became responsive to other antihypertensive therapy.

This article reviews aspects in the clinical presentation of nephrotic syndrome that are not generally considered characteristics of the syndrome's definition. The importance of various general clinical aspects such as hematuria, hypertension, and other laboratory or histologic findings are discussed. The clinical relevance and management of other specific aspects such as lipid alterations, coagulation abnormalities, calcium and vitamin D metabolism, and nutritional complications derived from the nephrotic syndrome also are included in this review.

We studied the fractional excretion of bicarbonate (FE HCO3) in 10 low birth weight infants aged 1–6 days during metabolic acidosis (base excess ≥ ––5 mEq/l) and during subsequent sodium HCO3 infusion. The mean birth weight was 1,095 g; the mean gestational age was 29 weeks. The ability to decrease urine pH to < 5.5 and FE HCO3 to < 1 % during metabolic acidosis was not limited by low gestational age or birth weight. After HCO3 therapy, all infants corrected their negative base excess, and plasma HCO3 increased significantly. All infants with blood pH ≤ 7.22 or PaCO2 ≥ 50 mm Hg had minimal or absent FE HCO3. Infants with elevated PaCO2 and mild or absent acidosis also had complete HCO3 tubular reabsorption. These results suggest that the HCO3 tubular reabsorption is adequate during metabolic and/or respiratory acidosis in low birth weight infants.

A simple technique of manometric scintigraphic retrograde cystography was applied prospectively to 125 patients (85 per cent children) with 142 studies. 99mTechnetium sulfur colloid (0.5 to 1 mCi.) was instilled in the bladder followed by increments of normal saline under manometric control. The sensitivity of the test was increased when the filling phase was concluded at 25cm. water pressure rather than when the patient complained of fullness (usually at 15cm.). The studies had a voiding phase that was essential for patients in whom pressures greater than 15cm. could not be achieved. Reflux was not detected on the voiding phase alone in 5 patients and the voiding phase could not be performed in 5 of 34 positive studies. It was not possible to predict volumes of fluid instilled to achieve satisfactory pressures. Monitoring during the entire study was necessary to diagnose reflux, which may occur at low or high pressure, or while voiding only.

THE ASSOCIATION of hyperuricemia with glycogen-storage disease (GSD) type 1 or von Gierke's disease has been described in 20 patients.1In some of these patients gouty arthropathy and nephropathy have occurred.2-4The mechanism responsible for hyperuricemia has not been delineated, but is thought to result from altered renal tubular function.5Normally, 90%-95% of the uric acid which is filtered at the glomeruli is reabsorbed by the proximal renal tubules. The major portion which appears in the urine seems to be secreted by the distal renal tubules.6It has been hypothesized that the hyperlacticacidemia which these patients manifest either enhances renal tubular reabsorption or inhibits renal tubular secretion of uric acid, thereby decreasing uric acid clearance (Cur) and producing hyperuricemia.3 The purpose of this study was to determine the effect of lactic acid and glucose in the development of hyperuricemia in patients with GSD type

The campomelic (from the Greek "bent limbs") syndrome is characterized by dwarfism, peculiar facies with cleft palate, numerous cartilage and osseous anomalies including prenatal bowing of the lower extremities with pretibial skin dimpling, respiratory distress, generalized hypotonia, and neonatal death. The clinical, radiographic, and pathologic findings in three cases are presented. Absence of the olfactory nerves in two of the patients and tracheobronchial and ear deformities in all three patients indicate that the process is not restricted to the skeleton. The tracheobronchial hypoplasia significantly contributed to respiratory distress and neonatal death. No common denominator could be established among the three cases to indicate cause.