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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.

The authors from Miami discuss the problems affecting children with dysfunctional bladder syndrome. If there is progressive renal disease polyuria may overwhelm bladder capacity. They set out to determine whether overnight catheter drainage in such patients might have a beneficial effect. They found that this technique in patients with progressive polyuric renal failure may have the potential to preserve renal function in selected patients. They also state that it should not be seen as a replacement for surgical augmentation of the bladder or intermittent catheterization. OBJECTIVE To determine the possible beneficial effect of providing decompression of the collecting system by continuous overnight catheter drainage (COCD) in children with progressive renal disease and dysfunctional bladder syndrome, commonly associated with polyuria which may overwhelm bladder capacity. PATIENTS AND METHODS COCD was used in seven patients (four boys) with progressive polyuric kidney failure associated with dysfunctional bladders (current age 18.7 years, sd 5; age at COCD 12 years, sd 6). Five children had surgical bladder augmentation and all were prescribed daytime intermittent catheterization (IC) for a mean (sd) of 4.7 (3.4) years before COCD. All had significant polyuria, with a mean (sd) urine output of 2370 (971) mL/m2 per day. RESULTS The mean (sd) glomerular filtration rate at the start of COCD was 48 (21) mL/min/1.73 m2, which is currently stable in the five patients continuing treatment. The mean (sd) duration of COCD was 4.9 (2) years. One patient showed no improvement and had a pre-emptive transplant within 1.2 years; another was transplanted after 5.5 years. Six patients showed evidence of benefit from COCD, with significant attenuation in the slope of renal functional decay (P = 0.02) and a mean (sd) prolongation of the predicted time to end-stage renal disease of 12.2 (5.6) years (P

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.

A variable prevalence of hepatitis C (HCV) infection has been reported in adult patients on hemodialysis. We have studied HCV infection and associated risk factors in a pediatric dialysis unit. Sera from all 27 patients undergoing either hemodialysis or peritoneal dialysis in our unit were tested for antibody to HCV by enzyme-linked immunosorbent assay, and seropositives were confirmed by recombinant immunoblot assay. Records were reviewed for demographic, biochemical, and risk factor data. From the total of 27 patients (12 male, mean age 20.9 years, range 7.3 to 28.1 years), five were anti-HCV(+) (18.5%). All the anti-HCV(+) patients had been on hemodialysis (69 to 194 months, mean 105 months), while of the 22 anti-HCV(–) patients, only 14 had been on hemodialysis (5 to 209 months, mean 41.4 months), P < .005. All the anti-HCV(+) patients had received blood transfusions (10 to 124 units, mean 61.4 units) as had 12 of the anti-HCV(–) patients (1 to 54 units, mean 14 units), P < .02. Of the 5 anti-HCV(+) patients, only one had prior hepatitis B infection of the 22 anti-HCV(–) patients, three had hepatitis B surface antigen, and no others had evidence of hepatitis B infection. The most predictive risk factor for HCV infection was length of time on hemodialysis. Eleven of the 27 patients (40.7%) had abnormal alanine aminotransferase values, of whom four were anti-HCV(+), three were hepatitis B surface antigen(+), and one was seropositive for antibody to human immunodeficiency virus. Pediatric dialysis patients are at risk for HCV infection; the most predictive risk factor in this population is length of time on hemodialysis. Approximately one third of abnormal alanine aminotransferase values in pediatric dialysis patients may be caused by HCV.

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.

Major differences between human immunodeficiency virus (HIV) associated nephropathy (HIVN) in children and HIVN in adults include the following: HIVN occurs in both HIV-1 + and AIDS adults, but apparently only in AIDS children. In HIVN patients, the virus has been transmitted to adult males mostly by intravenous drug use, and to adult females mostly by intercourse with infected males, but the virus has been transmitted to male and female infants and children by the mother. Renal histology changes in HIVN adults are mostly of the focal and segmental sclerosis (FSS) type, but FSS type changes are found in only one-third-one-half of HIVN children. The onset of chronic renal failure in adults heralds a rapid (few weeks) course to death, but in children the course is much slower (several months). Acute renal failure is rarely diagnosed in HIVN children while it is commonly diagnosed in HIVN adults.

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.

A cohort of 263 children with perinatally transmitted HIV infection was followed prospectively at the University of Miami/Jackson Children's Hospital for the development of overt HIV infection and associated nephropathy (HIVN). Definitive HIV infection was confirmed by persistent titers of HIV antibodies and/or positive viral PCR assays after 18 months. Nephropathy was defined in patients determined to have persistent proteinuria greater than or equal to 1+ on urinary Dipstick(R) in the absence of fever on consecutive urines at least 2 weeks apart. Quantitation of proteinuria was performed by timed collections(UprV) or urine protein: creatinine ratios (Upr/Ucr). Significant proteinuria was defined as a UprV≥0.1 gram/m2/day or Upr/Ucr≥0.2. Nephrotic proteinuria was defined as UprV≥1 gram/m2/day or Upr/Ucr≥2. The racial and ethnic demographics of the population were predominantly Black(74%) with the remainder Hispanic (14%) and Caucasian (12%). 72 of the 263 children developed active HIV infection. Of these, 44 had persistent proteinuria making the actual incidence of HIVN as high as 54%. Twelve of the 44 (16.7%) had nephrotic range proteinuria. The overall mortality for the HIV+ children not attributable to renal disease has been 50% over 5 years. Only 6(13.6%) have progressed to end stage renal disease (ESRD) requiring dialysis. All were of African-American or Haitian descent. The renal pathology in all ESRD patients was focal glomerulosclerosis with nephrotic range proteinuria preceding the deterioration to ESRD. The mortality of the HIV+ dialysis patients was not different from the rest of the HIV+ children in the study. These data suggest a strong influence of race and ethnicity in the development and progression of HIVN in the pediatric population.

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.

A variety of renal structural and functional abnormalities have been associated with sickle cell disease. To define the relationship between the hemoglobinopathy and glomerular disease, clinicopathologic correlations, renal morphologic, ultrastructural immunohistologic and functional studies were performed on seven patients with clinical and laboratory evidence of glomerular disease. In addition, immunologic studies including isolation and characterization of cryoprecipitable immune complexes, and determination of immunoglobulin, total complement and complement component levels, and antibody titers to several antigens were performed in an attempt to define the etiologic and pathogenic mechanisms of the renal disease and its relationship to sickle cell anemia. Proteinuria was presnet in all patients. The nephrotic syndrome, hypertension, hematuria and renal insufficiency were found in more than one half the patients. All patients had membranoproliferative glomerulonephritis of varying degree; glomerular basement membrane splitting, electron dense deposits in the glomerulus; interstitial fibrosis, tubular atrophy and hemosiderin deposits were frequent. Immunoglobulin complement components (classif complement pathway) and renal tubular epithelial antigen were distributed in a granular pattern along the glomerular basement membranes of all patients studied by these methods. Cyroprecipitable complexes of renal tubular epithelial antigen-antibody to renal tubular epithelial antigen as well as antibody to renal epithelial antigen were detected in the circulation of some patients. There was no serologic evidence of activation of the alternate complement pathway. These studies demonstrated an immune deposit normocomplementemic nephritis associated with sickle cell anemia; they further support our hypothesis that the relationship is more then coincidental, and is mediated by glomerular deposition of immune complexes of renal tubular epithelial antigen-antibody to renal tubular epithelial antigen, the antigen possibly released after tubular damage secondary to oxygenation and hemodynamic alterations related to sickle cell disease.

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.

Factors influencing bone and mineral metabolism were evaluated in 16 children with active nephrotic syndrome and normal glomerular filtration rate. All patients were proteinuric and/or hypoalbuminemic and had elevated serum triglyceride and cholesterol levels. Seven patients had never received or had discontinued glucocorticoid treatment at least 6 months before the study; six patients were receiving prednisone at the time of study. Although all patients were hypocalcemic (serum total or ionized calcium), none was hypomagnesemic. Despite the low serum calcium levels, circulating immunoreactive parathyroid hormone was elevated in only nine of 16. Plasma 25-hydroxyvitamin D was low in all 16 patients, averaging 7.6 ± 1.2 ng/mL for the group. In contrast, levels of 1,25-dihydroxyvitamin D were normal in 12 of 14 patients. Bone mineral content measured by photon absorptiometry averaged 83% and was less than 90% of normal in six of nine patients tested. The findings were not influenced by the recent or concurrent administration of glucocorticoid. The data demonstrate abnormalities of mineral and bone modulation in nephrotic children even in the absence of impaired glomerular filtration rate and irrespective of glucocorticoid therapy. The decrease in serum ionized calcium may be related to an absolute deficiency in 25-hydroxyvitamin D and/or a relative deficiency in 1,25-dihydroxyvitamin D. Undermineralization of bone may result from the low levels of vitamin D metabolites and, in some patients, from an increase in immunoreactive parathyroid hormone. Whether treatment with vitamin D metabolites and/or calcium supplementation will prevent the abnormalities remains to be demonstrated.

Renal function was studied serially in 17 healthy term infants during the hours immediately following birth. Of 14 infants delivered vaginally eight received placental blood transfusion and six did not. The remaining three infants were delivered by cesarean section and received placental blood transfusion. Results indicate that the general pattern of change in urine output (V), clearance of inulin (CIN), and p-aminohippuric acid (CPAH), was similar in all infants despite a wide range in each of the functions measured. The pattern showed an initial increase in V, CIN, and CPAH followed by a decline to low values in all infants by 3 hours of age. Urine osmolality and output generally changed in opposite directions. During the first hour the values for V ranged from 0.02 to 0.47 ml/min; for CIN, from 0.5 to 9.1 ml/min; for CPAH, from 1.4 to 21.8 ml/min; and for osmolality, from 98 to 457 mOsm/kg. By 4 hours of age the values for V ranged from 0.01 to 0.15 ml/min; for CIN, from 0.8 to 3.7 ml/min; for CPAH, from 0.8 to 7.5 ml/min; and for osmolality, from 240 to 520 mOsm/kg. The initial values of V, CIN, and CPAH, as well as the changes, were greatest in those infants who received a placental transfusion; however, there were no statistical differences among the means of the various groups. By 4 hours of age, the range of values observed in the initial measurement was much less pronounced. This probably reflects the achievement of stability of renal circulation following adaptation to a variety of stresses during the intrapartum period.

The relationship between V, CIN, and CPAH before and during diuresis as a result of infusion of D5W is shown in Figs 3 and 4; the relationship between V, osmolal clearance (COSM), and free water clearance (CH2O) is represented in Figs 5 and 6. The various clearances have been plotted against urine volume and compared with the regression lines for 17 infants (including seven in this paper) during the first three hours of life and prior to receiving an infusion.4 Despite a considerable scatter of data, there is no significant difference in the various correlations before and after infusion. A small decrease in fractional water reabsorption was observed after infusion, but not during spontaneous diuresis. No change in fractional osmolal reabsorption was observed during either spontaneous or infusion diuresis (Tables 2 and 3). In Table 4 the mean changes in the various measurements of renal function measured with infusion are compared with those occurring during spontaneous diuresis in the same infants. Again, except for the percentage of water reabsorbed after the infusion, there were no differences in the responses with the spontaneous diuresis compared to those observed after the infusion. See Images in the PDF File See Images in the PDF File See Images in the PDF File See Images in the PDF File See Table in the PDF File DISCUSSION Newborn infants during the first four hours of life are capable of having a prompt diuresis in response to an infusion of isotonic glucose. This diuresis is accompanied by an increase in renal plasma flow (RPF) and glomerular filtration rate (GFR).

The treatment of status asthmaticus (epinephrine-fast state in an acutely ill asthmatic patient) has been described frequently; however, the need to correct the respiratory and metabolic acidosis which accompanies this condition has not been emphasized. Recently such recommendations have appeared in the nonpediatric literature of this country and of Europe. The purpose of this paper is to report two pediatric patients with status asthmaticus who recovered after administration of Tris (hydroxymethyl) aminomethane (THAM), an amine alkalinizing agent. Methods The Astrup technique employing the ME-l equipment and Sigaard-Andersen's nomogram were used to determine pH, pCO2, Base Excess (B.E.), Buffer Base (B.B.) and Standard Bicarbonate (S.B.) of capillary blood. Serum electrolytes were determined by conventional methods. [SEE TABLE I AND II IN SOURCE PDF].

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)

The idiopathic nephrotic syndrome (NS) in children is usually defined by the presence of heavy proteinuria, hypoalbuminemia, edema and moderate to severe hyperlipidemia (1). Hyperlipidemia Type 2B with increase in serum cholesterol and triglycerides is the most common and recognized metabolic complication in patients with NS. However, the precise mechanisms involved in its pathogenesis, the associated clinical complications of hyperlipidemia and the best approach for its management are not well established.

Dialytic treatment of the newborn infant is a complex issue. Many neonatologists are reticent to institute this type of therapy with the many technical complications and risks inherent in the procedure. Those infants who might be considered in need of dialytic treatment are usually so profoundly ill as to increase the relative risk of the procedure. In fact, from a second vantage, one might suppose that the high mortality of neonates treated with dialysis comes from the delay incurred while contemplating the risk.

Hypocalcemia, defined as a serum calcium (Ca) concentration ≤ 7.5 mg/dl, constitutes a frequent development during the neonatal period. Since Ca is transferred across the placenta into the fetus at daily rates of up to 150 mg/kg of fetal weight during the last trimester of pregnancy, it is not surprising that upon delivery, the sudden interruption of such a rich supply of calcium should result in hypocalcemia. The latter has two main peaks of occurrence: during the first 48 hours following delivery (early hypocalcemia), or after the second part of the initial week of life (late hypocalcemia or classical neonatal tetany) (1). Early hypocalcemia is dealt with in detail in another chapter of this volume; however, since several mechanisms seem to be operative in both early and late hypocalcemia, some degree of overlap is unavoidable. This chapter attempts to summarize the available information related to the pathogenetic mechanisms involved in late neonatal hypocalcemia (Table 1).