Adrian Spitzer

The Use of Plasma Creatinine Concentration for Estimating Glomerular Filtration Rate in Infants, Children, and Adolescents

The formula GFR = kL/Pcr can be used to estimate GFR in infants, children, and adolescents who have grossly normal body habitus and are in steady-state condition. GFR is expressed in ml/min per 1.73 m2 BSA, L represents body length in cm, Pcr represents plasma creatinine concentration in mg per dl and k is a constant of proportionality that reflects the relationship between urinary creatinine excretion and units of body size. The value of k varies as a function of age and sex being 0.33 in preterm infants, 0.45 in full-term infants, 0.55 in children and adolescent girls, and 0.70 in adolescent boys. The advantages of rapid determination, reasonable accuracy, and the avoidance of urine collection justify the use of this formula in pediatric patients.

Plasma creatinine and urea concentration in children: Normal values for age and sex

cytes forming rosettes with sheep erythrocytes and HTL antigen negative lymphocytes interacting with antigenantibody-complement complexes, Clin EXp lmmunol 14:319, 1973. 2. Yata J, and Tsukimoto I: Maturation of cell surface structure of human B. lymphocytes, Lancet 2:1435, 1972. 3. Darzynkiewicz Z, and Jacobson B: HEPES-buffered media in lymphocyte cultures, Proc Soc Exp Biol Med 136:387, 1971. 4. Lar~dolt RF: Das Knochenmark bei Pertussis, Helv Med Acta 2:153, 1945. 5. Morse SI: Studies on the lymphocytosis induced in mice by bordetella pertussis, J Exp Med 121:49, 1965. 6. Morse SI, and Riester SK: Studies on the leukocytosis and lympbocytosis induced by bordetella pertussis. II. The effect of pertussis vaccine on the thoracic duc~ lymph and lymphocytes on mice, J Exp Med 125:619, 1967. 7. Morse S!, and Riester SK: Studies on the leukocytosis and lymphocytosis induced by bordetella pertussis. I. Radioautographic analysis of the circulating cells in mice undergoing pertussis-induced hyperleukocytosis, J Exp Med 125:401, 1967. 8. Miale J B: Laboratory medicine: Hematology, ed 4, St. Louis, 1972, The C. V. Mosby Company, p 906.

Renal tubular acidosis in infants and children: Clinical course, response to treatment, and prognosis+

Nine children with proximal renal tubular acidosis and four with distal renal tubular acidosis have been followed for periods ranging from six months to eight years. The patients with proximal renal tubular acidosis, predominantly male, presented with growth retardation and acidemia at ages 2 to 19 months. Treated with high-dose alkali therapy, most of these patients have shown improvement in growth rate. Now, one to eight years after diagnosis, seven of the nine patients are completely normal without therapy. The patients with distal renal tubular acidosis, 2 boys and 2 girls, presented at ages 4 to 13 years with growth retardation, polyuria, and recurrent episodes of acidosis and dehydration. Three had nephrocalcinosis and hypokalemia, and all demonstrated a renal concentrating defect. Three to eight years after diagnosis these patients continue to require low-dose alkali therapy; the renal concentrating defect and nephrocalcinosis persist, although the glomerular filtration rate has normalized.

Functional and Morphologic Maturation of the Superficial Nephrons RELATIONSHIP TO TOTAL KIDNEY FUNCTION

The functional and morphologic pattern of superficial nephron development was studied in guinea pigs ranging in age between 2 h and 38 days. Concomitent measurements of total kidney function and glomerular counts were also performed. Superficial nephron glomerular filtration rate was found to increase from 0.92 to 19.32 nl/min. The filtration rate of the entire kidney rose from 0.19 to 1.31 ml/min. During the first 15 days of life the average rate of increase in glomerular filtration rate per nephron (0.48 nl/min.day), obtained by dividing the increase in total kidney glomerular filtration rate by glomerular number, was more than twice the observed rate of increase in the superficial nephrons (0.21 nl/min.day). During the remainder of the first month, the increase in superficial nephron glomerular filtration rate (0.97 nl/min.day) was greater than the average increase for all nephrons (0.71 nl/min.day). Thus, the initial increase in total kidney glomerular filtration rate was primarily a consequence of the activity of the deep nephrons, whereas during the ensuing period the superficial nephrons appeared to be the sole contributors to the change in total kidney glomerular filtration rate.The increase in superficial nephron glomerular filtration rate was found to correlate closely with the increase in proximal tubular length. Functional glomerulotubular balance was maintained throughout the entire period of renal maturation.

The maturing kidney: A modern view of well-balanced infants with imbalanced nephrons†

In 1951 Smith wrote: “It is not inappropriate to point to the history of renal physiology as typical of the history of science, and particularly of the history of medicine. It has been a history of rival theories, each based upon inconclusive evidence. Its errors have been compounded by oversimplification in the matter of theory and underexamination in the matter of critical investigation. Renal physiology has now passed into a quantitative phase where unsupported speculation and empirical description are no longer warranted.”

Postnatal Changes in Renal Glomerular Blood Flow Distribution in Puppies

The intrarenal distribution of radionuclide microspheres injected into the thoracic aorta was used to examine glomerular blood flow distribution (GBFD) in 26 healthy, unanesthetized puppies, ranging in age from 5 h to 42 days, and in 5 adult dogs. For analysis, the cortex was divided into four equally thick zones designated zone I (subcapsular) to zone IV (juxtamedullary). During the first 36 h of life, the highest flow rate was in zone II, which received 35.5+/-2.0%/g, compared with 26.8+/-1.4% to zone I, 23.7+/-1.4% to zone III, and 13.4+/-1.4% to zone IV. At age 6 wk, zone I had the highest rate of perfusion (48.6+/-2.1%, compared with 28.8+/-1.4% in zone II, 15.8+/-0.8%, in zone III, and 6.8+/-0.6% in zone IV). The 6-wk old animals resembled the adult animals, except for relatively greater perfusion per gram of zone I in the former group. Changes in relative GBFD did not correlate with those in arterial pressure or peripheral hematocrit. The distribution of glomeruli among the four zones of the cortex followed its own pattern of development. At birth and at 6 wk, the greatest density of glomeruli was in zone I (50.6+/-5.4 and 42.7+/-3.9%/g respectively, as compared with 24.1+/-2.9% in adults); in adults zone II contained the greatest density (39.1+/-1.6%). At birth the relative perfusion of glomeruli in zone I was only one-fifth that of glomeruli in zone IV, with intermediate values in zones II and III. By 6 wk of age, increased perfusion of the outer cortical glomeruli resulted in rates of flow in the four zones that did not differ significantly from each other. Relative perfusion in zone I continued to increase, so that in the adult animals perfusion in that zone was significantly greater than in the three deeper zones. These data demonstrate the marked hemodynamic changes that take place within the kidney during the first few weeks of life. The relatively greater blood flow of the most deeply situated nephrons in the early postnatal period suggests ascendancy of this population of nephrons and may have important functional implications.

The congruence of creatinine and inulin clearances in children: Use of the Technicon Auto Analyzer

TI-IE U S ~ F U L N ~ . S S and validity of the clearance of endogenous creatinine as an estimate of the rate of glomerular filtration has generated continuous debate since its introduction by Rehberg 1 in 1926. Any other procedure provoking such controversy would have been discarded long ago; however, the lack of an acceptable substitute, offering to the clinician a practical, reasonably reliable estimate of glomerular filtration rate (GFR) , explains the continued popularity, of the creatinine clearance. One of the serious objections to the creatinine clearance is that the commonly employed Jaff6 reaction measures not only creatinine, but also a variety of other socalled noncreatinin6 chromogens. 2 Thus the apparent value of blood creatinine determined with this method is erroneously and unpredictably high, serving to depress clearance values. On the other hand, the moiety of urinary creatinine contributed by tubular secretion increases the clearance, particularly

The renin angiotensin system in newborn dogs: developmental patterns and response to acute saline loading.

Summary: Plasma renin (PRC) and aldosterone concentrations are known to be high during early postnatal life. Whether this is related to the low rates of renal blood flow or to sodium homeostasis remains unknown. Measurements of PRC, renal blood flow, and its intrarenal distribution were performed in 1- to 3-wk-old puppies subjected to maneuvers known to stimulate or inhibit renin release. In the awake state, PRC was observed to be higher in 2-wk-old puppies than in older or younger dogs, (P < 0.0001). Significant differences in PRC were also found between litters (P < 0.0001), but they did not account for the age-related changes. Anesthesia resulted in a 3- to 5-fold rise in PRC, whereas saline expansion suppressed PRC at all ages, the fall tending to become progressively greater with age (P < 0.09). There was no significant correlation between the age-related changes in PRC and those in renal blood flow or its intrarenal distribution. The results of these experiments demonstrate that in the newborn from a qualitative point of view, PRC changes appropriately in response to various stimuli. However, quantitative age-related differences exist in this regard, reflecting an initial immaturity of the feedback system.Speculation: The lack of correlation between plasma renin concentration and the intrarenal distribution of blood flow, corroborated with the existence of a relationship between plasma renin and the state of the extracellular fluid volume, suggest that during development the renin-angiotensin-aldosterone system is geared toward the maintenance of the positive sodium balance intrinsic to the process of growth.

Ontogeny of renal phosphate transport and the process of growth.

Abstract. The kidneys of infants and children reabsorb a high fraction of the filtered phosphate (Pi), as appropriate to the needs of a growing organism. This high Pi reabsorptive rate is associated with a high capacity (Vmax) of the Na+-Pi symport system. At the molecular level this high reabsorptive capacity appears to be due to the presence of a growth-specific Na-Pi cotransporter. Several experimental findings support this assumption. Firstly, the expression of NaPi-2 mRNA is, if anything, lower in the renal cortex of young animals than of adult animals. Secondly, polyA RNA obtained from growing animals depleted of NaPi-2 by specific hybridization with an antisense 16-mer induces Na+-Pi transport in oocytes. No induction of Na+-Pi transport was observed in oocytes injected with hybridized polyA RNA obtained from adult animals. Thirdly, polyA RNA derived from young rats, depleted of NaPi-2 by subtractive hybridization with adult animal renal cortical cDNA, retains its ability to encode for Na+-Pi cotransport in oocytes. Adult animal renal cortical polyA RNA, depleted of NaPi-2 by subtractive hybridization, failed to induce Na+-Pi uptake into oocytes. Fourthly, renal cortical polyA RNA from young animals, depleted of NaPi-2, contains a region that is highly homologous (80%–92%) with the corresponding region of other modulated NaPi (type II) transporters. Fifthly, this region is also present in the polyA RNA obtained from the renal cortex of newborn rats (1st week of life), despite the fact that NaPi-2 is absent at this early age. Lastly, Npt2 (–/–) knockout mice, although hypophosphatemic and phosphaturic, filter and reabsorb Pi at rates exceeding those that can be accounted for by the expression of type I and III transporters. Based on these observations it is reasonable to surmise that the high Vmax of the Na+-Pi cotransport system observed in the young is due to a large extent to the presence of a growth-specific NaPi transporter, homologous but not identical to already cloned type II NaPi transporters.

The significance of focal sclerotic lesions of glomeruli in children

To establish the relationship between the type of focal sclerotic lesion of glomeruli and the development of progressive renal disease, the clinical courses of 20 children with focal segmental and 7 with focal global sclerosis were analyzed. Only five patients, all of them with focal segmental sclerosis, did not have the nephrotic syndrome, although all had proteinuria. Results suggest that patients with focal global sclerosis have a course identical to that of children with the minimal lesion form of nephrotic syndrome: onset in early childhood, response to steroid therapy, and a relapsing, nonprogressive course. Focal segmental sclerosis, in constrast, is characterized by older age at onset, high incidence of nephritic symptoms, lack of response to steroid therapy, and a progressive course with histologic and functional deterioration. Since most published reports have not distinguished between these two entities, a more favorable prognosis in focal segmental sclerosis may be inferred than is actually the case.