Volume Of Glomerular Filtrate Research Articles

Association between Regular Exercise and Urinary Uric Acid Excretion in Chinese Adults: A Cross-sectional Study.

Regular exercise decreases the risk of hyperuricemia, which is related to reduced urinary uric acid excretion (UUA/UAE). However, few studies have assessed the association between regular exercise and UAE. We conducted this study to investigate their associations in the general population. This was a cross-sectional study that involved a total of 5513 Chinese community-dwellers, who reported data on physical exercise. Fasting morning spot urine was used to measure UUA and creatinine. UAE was primarily assessed by UUA to creatinine ratio (UCr) and secondly by excretion of uric acid per volume of glomerular filtration (EurGF) and fractional excretion of uric acid (FEua). Linear regression analysis was used to assess their associations. Of the included participants, their mean age was 55.1 ± 13.0 years, and 1984 (36.0%) undertook regular exercise. Compared with participants with regular exercise, those with irregular exercise or no exercise had higher UUA/UCr (0.36 ± 0.15 vs. 0.39 ± 0.15, P < 0.001), EurGF (0.23 ± 0.10 vs. 0.24 ± 0.11 mg/dL, P < 0.001), and FEua (0.07 ± 0.04 vs. 0.08 ± 0.04, P = 0.006). These associations remained significant after controlling for multivariable including serum uric acid (SUA) or upon the exclusion of participants with renal dysfunction or urinary tract infection. In conclusion, regular exercise might be associated with decreased UAE, independent of SUA, in Chinese community-dwellers.

PECULIARITIES OF IONOREGULATORY RENAL FUNCTION OF RATS IN THE DYNAMICS OF EXPERIMENTAL DIABETES MELLITUS DEVELOPMENT WITH UNDERLYING PHARMACOLOGICAL BLOCADE OF RENIN-ANGIOTENSINALDOSTERONE SYSTEM

The aim of the study – to explore the role of the renin-angiotensin-aldosteronesystem (RAAS) in the disturbance of ionoregulatory renal function in alloxan-inducedexperimental diabetes mellitus (EDM).Material and methods. The experiments were carried out on 78 white non-linearmature male rats with 11-, 26- and 46-day long alloxan-induced EDM with underlyingpharmacological blockade of RAAS by administration of kaptopril. The study ofionoregulating function of the kidneys was provided by the clearance method under thecondition of water 2-hour diuresis.Results. Pharmacological blockade of RAAS in rats with alloxan-induced EDM causedan intensification of natriuresis at all stages of the experiment: increased urinaryconcentration of sodium ions, its excretion and clearance. On the 11th day of EDM, thesodium filtration charge increased with the development of hyponatremia, proximal anddistal sodium reabsorption standardized in volume of glomerular filtrate (GF) decreased,kaliuresis was suppressed, and sodium-free water clearance elevated. In case of 26-daylong EDM, the sodium filtration charge decreased, its absolute and relative reabsorption,the distal sodium reabsorption standardized by GF increased. Kaliuresis increased. In46-day long EDM, the sodium filtration charge decreased, and hyponatremia enhanced.Absolute and relative sodium reabsorption reduced due to both – proximal and distal.Kaliuresis augmented, the clearance of sodium-free water declined.Conclusions. The increase in urinary sodium loss during the 11-day EDM is stipulatedby glomerular hyperfiltration, causing a functional weakening of the tubulotubularbalance and relative dysfunction of the distal segment of the nephron, emphasizing therenoprotective effect of RAAS on ionoregulatory function of the kidneys. The decrease inthe total reabsorption potential of the tubular segment of the nephron in the dynamics ofEDM development reflects on the proximal tubules, and preserved tubulotubular balancecertifies functional intactness of the distal tubules in 26-day long EDM. RAAS pathologicalactivation and attenuation of the renal blood flow autoregulation by tubuloglomerularfeedback may serve as an initiating factor in the development of tubular disorders in 26-day long alloxan diabetes with following progression in 46-day long EDM.

The Association between Urinary Glucose and Renal Uric Acid Excretion in Non-diabetic Patients with Stage 1-2 Chronic Kidney Disease

ABSTRACT Aims: To test the hypothesis that in non-diabetic patients with early-stage chronic kidney disease (CKD), the renal excretion of urate and glucose transportation are coupled and interconnected. Methods: A cross-sectional study of 255 non-diabetic participants with stage 1–2 CKD recruited from our department was conducted. Spearman’s correlation and multiple linear regression analyses were used to study the correlation between urinary glucose and renal uric acid excretion. ANOVA was used to compare urinary uric acid excretion among three tertiles of urinary glucose (UG; UG1: UG<0.24 mmol/24 h/1.73 m2, UG2: 0.24 mmol/24 h/1.73 m2≤ UG≤0.55 mmol/24 h/1.73 m2, and UG3: UG>0.55 mmol/24 h/1.73 m2), the fractional excretion of glucose (FEG; FEG1: FEG<0.04%, FEG2: 0.04%≤FEG≤0.09%, and FEG3: FEG>0.09%) and the excretion of glucose per volume of glomerular filtration (EgGF; EgGF1: EgGF<1.95 μmol/L, EgGF2: 1.95 μmol/L≤ EgGF≤3.99 μmol/L, and EgGF3: EgGF>3.99 μmol/L). Results: According to the multiple linear regression analysis, FEG and EgGF were positively correlated with the excretion of uric acid per volume of glomerular filtration (EurGF) after adjusting for confounding factors. The EurGF levels in the highest tertiles of UG, FEG and EgGF were higher than those in the lowest tertiles of UG, FEG and EgGF. Conclusion: Urinary glucose excretion is closely related to renal excretion of uric acid in non-diabetic patients with stage 1–2 CKD.

Peculiarities of acid-releasing renal function of rats in the dynamics of experimental diabetes mellitus with underlying pharmacological blockade of renin-angiotensin-aldosterone system

Annotation. The aim of the study was to explore the peculiarities of acid-releasing renal function of rats in the dynamics of alloxan-induced experimental diabetes mellitus (EDM) with underlying pharmacological blockade of the renin-angiotensin-aldosterone system (RAAS). The experiments were carried out on 78 white non-linear mature male rats with 11-, 26- and 46-day long alloxan-induced EDM with underlying pharmacological blockade of RAAS by administration of captopril. The study of acid-releasing renal function was provided under the condition of water 2-hour diuresis by changes in urine pH, excretion of titrated acids (TA), ammonia and active hydrogen ions with calculations of their excretion and ratio indices, standardization per 100 μl of glomerular filtrate (GF) volume. It was found that after administration of captopril to rats with 11-day long EDM urine pH, excretion of active hydrogen ions, ammonia excretion increased, TA excretion reduced, including it standardized by the volume of GF, as well as standardized excretion of ammonium compounds. After captopril administration to the animals with a 26-day long EDM, urine pH and TA excretion raised, and the excretion of ammonium and hydrogen ions decreased, still exceeding the control values. Standardized by GF, these indices changed similarly. After pharmacological blockade of RAAS on the 46th day of EDM urine pH, TA excretion, including it standardized by GF, excretion of hydrogen ions enhanced. Excretion of ammonium compounds, including it standardized by GF, and standardized excretion of hydrogen ions declined as compared with control parameters. Thus, the intensification of acid-release at the early stages of EDM is systemic by character and develops due to glomerular hyperfiltration, overload of the nephron with acidic products of metabolism and accompanied by structural intactness of the tubular apparatus of the kidneys. Prolonged glomerular hyperfiltration, probably, is the initiating damaging factor for the tubular apparatus of the diabetic kidney, which in 26-day long EDM is accompanied by the inability of enzyme systems of tubular epithelial cells of proximal tubules, mostly, to provide adequate ammoniogenesis, despite the high efficacy of renal transport mechanisms of acid-release. Proximal tubulopathy on the background of augmented aciduria in animals with 46-day long EDM causes relative functional insufficiency of the distal tubular apparatus.

Efficacy of different urinary uric acid indicators in patients with chronic kidney disease

BackgroundMounting studies have shown that hyperuricemia is related to kidney diseases through multiple ways. However, the application of urinary uric acid indicators in patients with reduced renal function is not clear. In this study, we aim to determine the effects of renal function on various indicators reflecting uric acid levels in patients with chronic kidney disease (CKD).MethodsAnthropometric and biochemical examinations were performed in 625 patients with CKD recruited from Dept of Nephrology of Huadong hospital affiliated to Fudan University. Multiple regression analyses were used to study correlations of the estimated glomerular filtration rate (eGFR) with serum uric acid (SUA) and renal handling of uric acid. For further study, smooth curve plots and threshold effect analyses were applied to clarify associations between renal function and uric acid levels.ResultsThe nonlinear relationships were observed between eGFR and urinary uric acid indicators. The obvious inflection points were observed in smooth curve fitting of eGFR and fractional excretion of uric acid (FEur), excretion of uric acid per volume of glomerular filtration (EurGF). In subsequent analyses where levels of eGFR< 15 mL/min/1.73m2 were dichotomized (CKD5a/CKD5b), patients in the CKD5a showed higher levels of FEur and EurGF while lower levels of urinary uric acid excretion (UUA), clearance of uric acid (Cur) and glomerular filtration load of uric acid (FLur) compared with CKD5b group (all P < 0.05). And there was no significant difference of SUA levels between two groups. On the other hand, when eGFR< 109.9 ml/min/1.73 m2 and 89.1 ml/min/1.73 m2, the resultant curves exhibited approximately linear associations of eGFR with Cur and FLur respectively.ConclusionFEur and EurGF showed significantly compensatory increases with decreased renal function. And extra-renal uric acid excretion may play a compensatory role in patients with severe renal impairment to maintain SUA levels. Moreover, Cur and FLur may be more reliable indicators of classification for hyperuricemia in CKD patients.

Parathyroid changes after high dose radioactive iodine in patients with thyroid cancer

The study aimed to investigate the effect of high dose radioactive iodine (RAI) on parathyroid function in patients with differentiated thyroid cancer. Nineteen patients (8 men/11 women, age 46.5 +/- 13.2 years) undergoing RAI for thyroid remnant ablation were enrolled in the study. The biochemical parameters related to parathyroid function [serum calcium (Ca), phosphate (P), creatinine (Cr), alkaline phosphatase (ALP), intact parathyroid hormone (iPTH), urinary Ca, cAMP concentrations and the maximum tubular capacity for phosphate per unit volume of glomerular filtrate (TmP/GFR)] were evaluated at baseline and at the 1st, 3rd, 6th and 12th months of RAI administration. SPSS 15.0 was used for statistical analysis. For all patients, thyroid-stimulating hormone levels were >30 U/ml at baseline and <0.1 U/ml at the following visits. Serum iPTH levels were decreased significantly at the 6th month and reached basal levels at the 12th month (baseline vs. 6th p = 0.027, 1st vs. 6th p = 0.011, 3rd vs. 6th p = 0.047, 3rd vs. 12th p = 0.014, 6th vs. 12th p = 0.001). At the 6th month, P and TmP/GFR levels were higher (p = 0.036, 0.017, respectively), and urinary cAMP measurements were lower (p = 0.020) compared to those of the 1st month. No difference was detected concerning the other parameters. Serum Ca levels decreased below 2.1 mmol/l in several patients (n = 5 at 1st month, n = 4 at 3rd month, n = 8 at 6th month and n = 3 at 12th month) without clinical symptoms. The study indicated a transient decline in PTH levels at the 6th month following RAI therapy. Although this decrease did not cause symptoms in any of the present cases, this pattern might be important especially in individuals with diminished parathyroid background.

Renal underexcretion of uric acid is present in patients with apparent high urinary uric acid output.

To compare renal handling of uric acid in patients with primary gout with that of a control group. A case-control study of 100 patients with primary gout and 72 healthy controls was undertaken. Creatinine clearance, uric acid clearance, 24-hour uric acid urinary excretion, fractional excretion of uric acid, excretion of uric acid per volume of glomerular filtration, urinary uric acid to creatinine ratio, and glomerular uric acid filtered load were calculated using 24-hour urine samples. After treatment with allopurinol to achieve similar glomerular filtered load of uric acid, patients were again compared with controls. Patients with gout showed lower uric acid clearance, fractional excretion of uric acid, excretion of uric acid per volume of glomerular filtration, and urinary uric acid to creatinine ratio than controls at baseline, when patients showed hyperuricemia. Although the glomerular uric acid filtered load was much higher in patients with gout than controls, 24-hour uric acid excretion was not statistically different. After treatment with allopurinol, and achieving similar uric acid filtered loads, patients still showed lower figures than controls. When patients with 24-hour urinary uric acids levels >700 mg/day were compared with controls, they had lower uric acid clearance and fractional excretion of uric acid than controls, both at baseline and after achieving similar filtered loads with allopurinol therapy. Renal underexcretion is the main mechanism for the development of primary hyperuricemia in gout, but even patients showing apparent high 24-hour uric acid output show lower uric acid clearance than controls, indicating that relative, low-grade underexcretion of uric acid is at work.

Renal adaptation to phosphate deprivation: lessons from the X-linkedHyp mouse

The X-linked Hyp mutation, a murine homologue of X-linked hypophosphatemia in humans, is characterized by renal defects in phosphate reabsorption and vitamin D metabolism. In addition, the renal adaptive response to phosphate deprivation in mutant Hyp mice differs from that of normal littermates. While Hyp mice fed a low phosphate diet retain the capacity to exhibit a significant increase in renal brush-border membrane sodium-phosphate cotransport in vitro, the mutants fail to show an adaptive increase in maximal tubular reabsorption of phosphate per volume of glomerular filtrate (TmP/GFR) in vivo. Moreover, unlike their normal counterparts, Hyp mice respond to phosphate restriction with a fall in the serum concentration of 1,25-dihydroxyvitamin D [1,25(OH)2D] that can be ascribed to increased renal 1,25(OH)2D catabolism. The dissociation between the adaptive brush-border membrane phosphate transport response and the TmP/GFR and vitamin D responses observed in Hyp mice is also apparent in X-linked Gy mice and hypophysectomized rats. Based on these findings and the notion that transport across the brush-border membrane reflects proximal tubular function, we suggest that the adaptive TmP/GFR response requires the participation of 1,25(OH)2D or a related metabolite and that a more distal segment of the nephron is the likely target for the 1,25(OH)2D-dependent increase in overall tubular phosphate conservation.

Expression of chronic thyroparathyroidectomy on phosphate transport in whole kidney and proximal luminal membranes during phosphate deprivation.

Both parathyroid hormone (PTH) and the dietary supply of inorganic phosphate (Pi) influence the tubular Pi reabsorptive capacity. In this study we have assessed how removal of parathyroid gland affects the response of Pi transport to Pi restriction in the whole kidney and in brush border membrane vesicles (BBMV) isolated from the renal cortex. Intact and thyroparathyroidectomized (TPTX) rats were switched from normal to low Pi diet. The maximal tubular Pi reabsorption per volume of glomerular filtrate (max. TRPi/ml GF) and the initial (3, 6 and 9 s) Na+-dependent Pi uptake by BBMV were determined before and after 1, 2, 3 and 8 days of Pi restriction. The results indicate that before Pi restriction max. TRPi/ml GF was 1.94 +/- 0.04 and 4.03 +/- 0.14 mumol/ml GF in intact and TPTX rats respectively. The corresponding Na+-dependent Pi uptake (3 s value) was 137 +/- 23 in sham and 272 +/- 41 pmol/mg protein in TPTX rats. During Pi restriction the initial difference in max. TRPi/ml GF remained constant throughout the time course study. At 8 days max. TRPi/ml GF was in intact 3.08 +/- 0.09 and in TPTX 5.04 +/- 0.18 mumol/ml GF. In sharp contrast, in BBMV the initial difference between intact and TPTX became completely abolished 8 days after starting the Pi restriction (SHAM = 425 +/- 69; TPTX = 434 +/- pmol/mg protein). In conclusion, the overall tubular Pi transport capacity and the Na+-dependent Pi transport system located in the luminal membrane of the proximal tubule appear to be quite differently affected by changes in the PTH status during Pi restriction.

Tubular handling of Pi in young growing and adult rats.

The tubular transport of inorganic phosphate (Pi) is controlled by a parathyroid hormone-independent mechanism that responds to variations in the Pi intake. This adaptation mechanism could also respond to growth-mediated variation in the utilization of Pi by the organism. In the present work we have determined the maximal net Pi reabsorption per volume of glomerular filtrate (max TRPi/ml GF) in the young growing (2-mo) and adult 8- to 9-mo) rats. Max TRP[i/ml GF was significantly lower in intact adult (1.44 +/- 0.06 mumol/ml) compared with intact young growing animals (2.22 +/- 0.12 mumol/ml GF). This difference was maintained after removal of the thyroparathyroid glands; adult, 2.89 +/- 0.25, young, 4.56 +/- 0.25 mumol/ml. It was not associated with a difference in the urinary excretion of cAMP, GFR, renal handling of sodium, plasma calcium, or acid-base status. Administration of growth hormone preparations to adult rats did not raise max TRPi/ml GF to the level observed in young intact animals. With regard to the tubular Pi adaptation to Pi restriction, lowering the phosphorus content in the diet from 0.8 to 0.2 g/100 g resulted in an attenuated and delayed enhancement in max TRPi/ml in adult as compared with the response observed in young growing rats. These results show that the decrease in tubular reabsorption of Pi that occurs when rats become adult in a parathyroid hormone-independent phenomenon. It is suggested that this change is an adaptation of the tubular Pi transport to a reduction in the utilization of Pi in relation to the diminished growth rate of the animals.

Abnormal tubular adaptation to dietary Pi restriction in X-linked hypophosphatemic mice

The renal handling of inorganic phosphate (Pi) is in part under the control of a powerful mechanism that is independent of parathyroid hormone and has the ability to enhance net tubular Pi reabsorption in response to a reduction in the Pi supply. The decreased renal reabsorption of Pi, the salient feature of the human disease X-linked hypophosphatemia, could be due to a loss of this adaptive capability of the tubular Pi transport system. To investigate this hypothesis, mutant hypophosphatemic (HYP) mice were used as a model of the human disease. Male HYP mice and normal littermates were subjected to high (0.75 g/100 g), low (0.25 g/100 g), or very low (0.03 g/100 g) phosphorus diets for periods varying between 1 and 20 days. Then the overall tubular Pi transport capacity was assessed by determining the maximal net Pi reabsorption per unit volume of glomerular filtrate (max TRPi/ml GF). The results indicate that the marked enhancement of max TRPi/ml GF, which is observed in normal mice after the first day of Pi restriction, is completely absent in HYP mice. In chronically thyroparathyroidectomized animals, 10 days of low phosphorus diet stimulated conspicuous max TRPi/ml GF in normal mice, whereas the same regimen did not significantly change the Pi reabsorptive capacity of HYP counterparts. The results of this study suggest that X-linked hypophosphatemia is a disease with a defect in the mechanism responsible for the adaptation of the tubular Pi transport system to Pi restriction.

Parathyroid hormone-independent adaptation of the renal handling of phosphate in response to renal mass reduction

In man as well as in experimental animals progressive renal failure is associated with a decrease in the fractional reabsorption (FR) of inorganic phosphate (Pi). This response has been considered as an adaptation phenomenon and generally attributed to an increase in parathyroid hormone (PTH) secretion. One report indicates that in chronic thyroparathyroidectomized (TPTX) dogs treated with large doses of vitamin D progressive renal failure can also be associated with a fall in FRPi. However, in this latter study the concomittant administration of vitamin D could have accounted for the observed decrease in FRPi. In our study we investigated whether or not chronic reduction in renal mass leads to a similar decrease in maximal net tubular Pi reabsorption per volume of glomerular filtrate (maximal TRPi/ml GF) in the presence and absence of PTH and without pharmacological supplementation in vitamin D. Male rats were either TPTX or sham-operated (intact). One and two weeks later the animals of both groups were either subtotally nephrectomized (NX) in two stages or sham-operated (control). Four weeks after the second renal operation, the glomerular filtration rate (GFR) and the reabsorption of Pi were determined by clearance methodology under acute sodium chloride and Pi infusion, that is, at endogenous and increased plasma Pi concentrations ([Pi]Pl.). Thus maximal TRPi/ml GFR could be determined. In rats with intact parathyroid glands GFR was 1.56 +/- 0.10 (mean +/- SEM) and 0.54 +/- 0.10 ml/min in control and NX respectively, whereas maximal TRPi/ml GF was 2.24 +/- 0.07 in control and 1.57 +/- 0.18 mumol/ml (P less than 0.005) in NX. In TPTX rats GFR was 1.66 +/- 0.27 and 0.62 +/- 0.06 ml/min in control and NX respectively, whereas maximal TRPi/ml GF was 3.80 +/- 0.20 in control and 2.95 +/- 0.13 mumol/ml (P less than 0.005) in NX. The marked decrease in maximal TRPi/ml GF observed in TPTX after subtotal NX could not be ascribed to any consistent change in plasma calcium. Our study provides conclusive evidence that the decrease in maximal TRPi/ml GF in response to renal mass reduction can occur to the same degree in the presence or absence of PTH.

Tubular adaptation to Pi restriction in hypophysectomized rats.

The renal tubule adapts its tubular transport capacity for inorganic phosphate (Pi) in response to a reduction in the Pi supply. In order to assess whether growth hormone plays a critical role in this adaptive response we have studied the change in the tubular handling of Pi which follows Pi restriction in hypophysectomized (HPX) rats and compared it to that occurring in intact counterparts. HPX and intact rats were maintained either on a 1.2 g/100 g phosphorus diet or fed a 0.2 g/100 g phosphorus diet for 3, 6 or 12 days. HPX rats received ACTH and thyroxine in doses which normalize their low glomerular filtration rate (GFR). Then the maximal net Pi reabsorption per volume of glomerular filtrate (max. TRPi/ml GFR) were determined during acute Pi infusion by clearance technique. The results indicate that HPX rats responded to Pi restriction by raising their tubular capacity to reabsorb Pi. However, the rapidity and the magnitude of the adaptive response was significantly less in HPX than in intact rats. The adaptation to Pi restriction was also observed in HPX rats after thyroparathyroidectomy. It is concluded that growth hormone and other pituitary hormones do not play a key role in the adaptive response to Pi restriction. The reduced adaptive response observed in HPX rats with intact thyroparathyroid glands could be due to the decreased Pi demand consecutive to impaired growth.

Extracellular volume: its structure and measurement and the influence of age and disease

Summary 1. Extracellular volume is an importantparameter of the body. Extracellular fluid surrounds the tissue cells and has a high chloride and low potassium concentration. Extracellular fluid is comprised of interstitial fluid (36 per cent), connective tissue water (35 per cent), and plasma, bone, and gastrointestinal water (29 per cent). Extracellular volume closely approximates, biochemically and morphologically, under physiologic conditions the volume of the corrected chloride space. The chloride space is defined as the volume of distribution of chloride in the body having a net concentration of chloride equal to that of a plasma ultrafiltrate (120 mEq. per liter). When this chloride space is corrected for chloride outside the extracellular fluid (red blood cell and visceral cell chloride), the resulting volume approximates true extracellular volume. Evidence is presented that 10 to 13 per cent of chloride is intracellular, and 10 per cent is taken as the correction factor. The chloride space can be conveniently measured with stable bromide since the distribution of these anions in the body is almost identical. 2. Data are presented on extracellular volume from the first day of life up through childhood. During the first year of life the volume comprises 47 per cent of total body water and during the second year 41 per cent. Chemical maturity is then reached and this relationship alters less noticeably with further maturation. 3. At various age levels the relation betweenextracellular volume and the volume of glomerular filtration per day is almost linear. The turnover of extracellular fluid through the glomerular membrane is greater in the infant than in the adult (maximum at 18 months). 4. Basal metabolic rate is linearly relatedto the volume in the older child and adult, but in the infant there is less fluid for each basal calorie. Since metabolic functions are accelerated in early life, the reserves of extracellular fluid at this time may be inadequate, particularly if “stress” supervenes and metabolism is raised further. 5. From a consideration of the differentialgrowth equation, evidence is presented that during growth a change in the mathematical relationship between body weight and extracellular volume occurs at about 5 kilograms in weight (6 weeks of age). It was known that the growth equation for total chloride and body weight in the fetus and newborn infant changed to a new equation at about that period. 6. Mention is made of pathologic changes in extracellular volume during early life, including some aspects of adrenal, renal, and gastrointestinal disease. Changes in volume due to malnutrition are discussed, and attention is drawn to fibrocystic disease of the pancreas, where evidence is presented that the volume is reduced in terms of total body water. Muscle data indicate that the sodium and chloride content is decreased in the disease. 7. Change in extracellular volume and sodium concentration in central nervous system disease are reviewed and the suggestion is made that the biochemical lesion seen in patients with tubercular meningitis is related to allergy. A brief note concerning “volume receptors” is included.

INTRACELLULAR COMPOSITION AND HOMEOSTATIC MECHANISMS IN SEVERE CHRONIC INFANTILE MALNUTRITION

The water and electrolyte compositions of serial biopsies of skin and muscle obtained from children with severe chronic malnutrition have been related to balance data, obtained simultaneously in some of them, and to renal adjustments during hypotonic dehydration. The composition of diarrheal stools and specimens of urine obtained daily are given. While the number of observations is limited, severe chronic malnutrition with imbalance of electrolytes or water would seem to be characterized by the following features: Extracellular hypotonicity with expansion of the aqueous intracellular phase in muscle of non-atrophic children irrespective of reduction or expansion in volume of the extracellular phase. Increase in the ratio of intracellular to extracellular content of water often is accompanied by accumulation of sodium within the cell, quite independent of content or concentration of potassium in the cell. Either the osmotic properties of the cell or cell metabolism, or both, are altered. This progression is accelerated by intercurrent events of acute nature and is reversed during recovery. Death resulting from dehydration (or infection) superimposed upon severe malnutrition may be associated with sudden further expansion of the intracellular phase at the expense of the extracellular fluids. Content of sodium in the cell increases markedly. Balance data obtained in one such patient could not be reconciled with change in composition of the tissue. Slow renal and tissue response to malnutrition leads to marked reduction in total mass of tissue, but reconstitution of surviving tissue, presumably by utilization of substances released by catabolism of cells. The etiology of the characteristic hypotonicity of the body fluids is not known. Hypotonicity probably results from release of endogenous water from catabolism of cells, depletion of protein, recurrent loss of water and solute in diarrheal stools, and an intake of water relatively in excess of solute. Overhydration of the intracellular phase is a consequence of the extracellular hypotonicity. Excretion of a relatively hypotonic urine is interpreted as a defense of concentration of solutes in the body water, and reduction in the volume of glomerular filtrate might be interpreted as a limiting defense for sustaining the volume of body water. Redistribution of body water with very prompt contraction of the overhydrated intracellular phase and expansion of the extracellular phase of the body may be achieved by infusion of hypertonic solutions to severely dehydrated, malnourished, hypotonic infants. However, further careful examination of this phenomenon is needed to define the limitations of infusion and response before extensive use of hypertonic solutions in therapy of even the extreme cases can be advocated with safety. An hypothesis is hazarded concerning the development of the biochemical lesions of the cells and tissues in chronic malnutrition. It is suggested that despite apparently different clinical features, chronic malnutrition with respect to proteins and calories in infants may be interpreted as a continuous process of disturbance at a cytoplasmic level which gradually narrows the flexibility of renal and cellular responses. Superimposed acute catabolic events like diarrhea or infection eventually overcome the limits of renal and of cellular compensation, thus leading to irreversible intracellular biochemical derangement and death.

The mechanism and significance of protein excretion by the normal kidney.

The supposition that the glomerular filtrate is protein-free is based on the classical experimental studies of Wearn and Richards. 1 They found glomerular fluid, obtained by micropuncture from Bowman's capsule, to be free or at least to contain less than 30 mg. per 100 ml. of protein, which was the least amount that could be detected by the methods at their disposal. As Addis 2 has pointed out, this supposition might be readily accepted were it not that the volume of glomerular filtrate in man is approximately 180,000 ml. per 24 hours, so that even if the protein concentration was as little as 10 mg. per 100 ml., 18,000 mg. would pass through the membrane daily. Considerations of this sort stimulated workers in the field, so that during the past 10 years our knowledge of the passage of proteins through the kidney has advanced to the point where a

Lack of correlation between symptoms and degree of renal impairment.

Excerpt In a recent publication from this laboratory1the work of Sirota, Baldwin and Villarreal,2showing that the 24-hourly volume of glomerular filtrate can be measured satisfactorily, was confirm...

Reabsorption of Certain Amino Acids and Derivatives by the Kidney Tubules

Evidence has been presented previously showing a marked variation in the extent of the excretion of different amino acids after their intravenous administration. This study was designed to measure the rates of tubular reabsorption of 1-tyrosine, N-acetyl-1-tyrosine, N-methyl-1-tyrosine and 1-histidine. The results were obtained by using sodium ferrocyanide to measure the rate of glomerular filtration during the period of study of each substance. The procedure is an adaptation of one elaborated by Van Slyke, Hiller and Miller. Dogs received an intraperitoneal injection of 200 cc of a solution containing a suitable amount of sodium ferrocyanide together with the compound being studied. After a lapse of 15 minutes the bladder was emptied by catheterization and washed with distilled water. The urine was collected for a period of approximately one hour. Tyrosine and its derivatives were determined by the Folin-Ciocalteu phenol reagent; histidine by the Jorpes modification of the Koessler-Hanke method. A sample of blood was obtained about 15 minutes after the beginning and again 15 minutes before the end of the experimental period. The average of the values for the 2 samples of blood was used in each calculation. Volume of glomerular filtrate was obtained by dividing 100 × mg of ferrocyanide excreted by the average mg % of ferrocyanide in the plasma. By using this volume of glomerular filtrate and the plasma concentration of amino acid it was possible to calculate the amount of amino acid in the glomerular filtrate. Knowing the amount of amino acid excreted one obtained by difference the amount of the amino acid reabsorbed by the tubules. From Table I it appears that only a small fraction of the acetyl derivative is reabsorbed whereas approximately two-thirds of the methyl derivative is taken up under similar conditions.