Assessment of kidney function in preterm infants: lifelong implications.

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.

A renal protocol for all ages and all indications: mercapto-acetyl-triglycine (MAG3) with simultaneous injection of furosemide (MAG3-F0): a 17-year 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.

Paricalcitol versus calcitriol treatment for hyperparathyroidism in pediatric hemodialysis patients.

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.

Role of routine urinalysis in asymptomatic pediatric patients.

This study was done to evaluate the spectrum of diagnoses and identify risk factors for significant kidney disease in asymptomatic children with proteinuria and/or microhematuria detected by routine urinalysis. Clinical and laboratory data were obtained by retrospective chart review of 239 patients referred to a tertiary care center. The predominant diagnosis in children with isolated microhematuria was hypercalciuria and with isolated proteinuria, orthostatic proteinuria. When microhematuria and proteinuria were present in combination, kidney disease was the predominant diagnosis. Urinalysis is a valuable tool to identify patients with kidney disease. The combination of microhematuria and proteinuria increases the risk of having significant kidney disease.

Recurrent focal glomerulosclerosis in pediatric renal allografts: the Miami experience.

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.

Novel therapy of focal glomerulosclerosis with mycophenolate and angiotensin blockade.

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 ( P<0.05). After 6 months of MMF-AB protocol, the Up/c was 72% below baseline ( P<0.01). 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, P<0.01). 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.