Renal sodium handling in children with nephrotic relapse: relation to hypovolaemic symptoms

We studied renal sodium handling during water diuresis in children in the early phase of relapse of minimal lesion nephrotic syndrome (MLNS). Findings were related to presence or absence of symptoms suggestive of hypovolaemia, and to neurohumoral factors, and were compared to results of similar studies in the same children in remission. Nine children (aged 7.8 +/- 3.1 years) presented with hypovolaemic symptoms, and 10 (7.4 +/- 4.3 years) without such symptoms. Both groups displayed severe proteinuria, hypoproteinaemia and oedema. Symptomatic patients showed tendency for a low glomerular filtration rate, and significantly impaired urine dilution, decreased fractional sodium and lithium excretions, and elevated diluting segment reabsorption [CH2O/(CH2O + CNa)] and sodium/potassium exchange [UK/(UK + UNa)]. In the non-symptomatic patients these parameters were normal. Plasma renin and aldosterone were significantly elevated in the symptomatic children, and strongly correlated with all parameters of tubule sodium reabsorption. Weaker associations were found for plasma noradrenaline and atrial natriuretic peptide. Vasopressin was also relatively high in the symptomatic group, but showed no association with impaired urine dilution. The diffusely stimulated tubular sodium reabsorption in the symptomatic children, in association with stimulated neurohumoral factors, indicates that secondary sodium retention contributes to oedema formation in at least a subset of children developing a nephrotic relapse. This may be limited to the early stage, and be more pronounced in some patients than in others. The tubular defect responsible for maintenance of oedema in stabilized MLNS remains unclear.     

Renal elimination of lithium in rats with lithium intoxication

The relation between urine flow (V), lithium clearance (CLi) and sodium clearance (CNa) was studied in rats given food containing lithium in amounts leading to inhibition of distal reabsorption of water and sodium. Maximum inhibition of the reabsorption of water was reached at serum lithium concentrations of about 1 mM. At higher serum lithium levels the rats developed intoxication due to a lowering of CLi and a consequent rise of the serum lithium concentration. The intoxication was characterized by a proportional decrease of V and CLi. The decrease of V and CLi was not related to changes of CNa. The results indicate that lithium is reabsorbed in the proximal tubules in parallel with sodium and that the lowering of CLi is due to increased fractional proximal reabsorption of lithium and sodium compensatory to inhibition of the distal reabsorption of sodium.     

Nephrotoxicity of cyclosporine in humans: effect of cyclosporine on glomerular filtration and proximal tubular reabsorption

The chronic nephrotoxic effects of cyclosporine (CsA) include proximal tubular atrophy and vacuolization. This study investigated the effect of CsA on renal hemodynamics and segmental electrolyte transport in CsA-treated patients. The clearance of inulin (CIn) and PAH para-amino-hippuric acid (CPAH) was determined; proximal tubular function was studied using a lithium clearance method and calculating tubular phosphate reabsorption per milliliter of glomerular filtrate (TP/CIn). Twenty patients without renal disease were investigated: ten treated with CsA because of nonrenal grafting (group 1) and ten healthy volunteers (group 2). The results obtained were compared with those from 20 renal allograft recipients, of whom ten were treated with CsA and methylprednisolone (group 3) and ten with azathioprine and methylprednisolone (group 4). CIn and CPAH were significantly impaired in patients treated with CsA. No significant impairment of lithium clearance as induced by CsA was observed. The fractional excretion of lithium was slightly increased in patients treated with CsA compared to their respective controls. TP/CIn was lower in graft recipients compared to controls; no impairment of phosphate reabsorption as induced by CsA was found. The fractional tubular excretion of lithium was slightly increased compared to controls, rising evidence that proximal tubular reabsorption of lithium was decreased. Tubular reabsorption of phosphate was not impaired. The decrease in glomerular filtration and renal perfusion during chronic treatment with CsA was accompanied by a reduced proximal reabsorptive capacity, as was shown by lithium clearance. Our data do not support the hypothesis that functional parameters of the proximal tubular system can be used as indicators of CsA-induced nephrotoxicity.     

Cardiorespiratory and renal responses to arterial chemoreceptor stimulation by hypoxia or almitrine in men

1. The cardiorespiratory and renal responses to 3 h of normobaric whole-body hypoxic hypoxia (FiO2 = 0.12) as well as to arterial chemoreceptor stimulation by the oral administration of 100 mg almitrine bismesylate during normoxia were measured in 12 normotensive young men undergoing water diuresis. A third series of responses obtained under comparable conditions in the same subjects served as time controls. 2. No significant changes could be detected over time in the parameters measured in control experiments. The subjects reacted to both whole-body hypoxic hypoxia and to pharmacological chemoreceptor stimulation with significant increases in heart rate, tidal volume, minute ventilation and filtration-fraction. Overall renal vascular resistance rose significantly in hypoxia; increases in renal vascular resistance in almitrine experiments were not significant. 3. Renal fractional lithium excretion decreased significantly in response to whole-body hypoxic hypoxia and increased slightly in response to almitrine. Fractional urine and sodium excretion showed negligible changes. 4. The data indicate that, in humans, both almitrine and whole-body hypoxic hypoxia affect not only alveolar ventilation but also renal haemodynamics. 5. The renal electrolyte excretion pattern suggests that under certain circumstances (e.g. dilated renal vascular bed) acute, but well-tolerated, whole-body hypoxic hypoxia can simultaneously stimulate renal proximal tubular sodium reabsorption and inhibit distal tubular sodium reabsorption. The renal tubular responses also indicate that almitrine may influence renal tubular lithium reabsorption by, thus far, unknown mechanisms.     

The influence of angiotensin-converting enzyme inhibition on renal tubular function in progressive chronic nephropathy

The influence of angiotensin-converting enzyme (ACE) inhibition on renal tubular function in progressive chronic nephropathy was investigated in 69 patients by the lithium clearance (C(Li)) method. Studies were done repeatedly for up to 2 years during a controlled trial on the effect of enalapril on progression of renal failure. The pattern of proteinuria was followed over the first 9 months. At baseline, the glomerular filtration rate (GFR) was 5 to 68 mL/min. Absolute proximal tubular reabsorption rate of fluid (APR), estimated as the difference between GFR and C(Li), was 1 to 54 mL/min. Calculated fractional proximal reabsorption (FPR) was moderately subnormal. During the study, GFR decreased and sodium clearance was unchanged; fractional excretion of sodium therefore increased. In the group of patients randomized to treatment with enalapril (n = 34), GFR at 1 month was 83% (P < 0.001) and C(Li) was 88% (P < 0.01) of the baseline values, APR and FPR had not changed significantly, and potassium clearance was significantly decreased. Through the rest of the study period, APR remained nearly unchanged and FPR even increased in the enalapril group. In the group of patients randomized to treatment with conventional antihypertensive drugs (n = 35), C(Li) was unchanged until severe reduction in GFR, APR and FPR decreased gradually, and potassium clearance was almost unchanged. These differences in tubular function between the two treatment regimens were significant (P < 0.05). An unchanged or increased APR in either treatment regimen was associated with a long-term slower progression of renal failure. Over 9 months, the 24-hour fractional clearance of albumin decreased in the ACE inhibitor group (P < 0.01), whereas the clearances of immunoglobulin G and retinol-binding protein were unchanged in this group. In the conventional group, the fractional clearances of these three plasma proteins all increased. It is concluded that in progressive chronic nephropathy ACE-inhibitor treatment was associated with different adaptive tubular changes in the handling of sodium, water, and protein compared with conventional antihypertensive therapy. During ACE inhibition, the reabsorptive capacity of the proximal tubule appeared to be better preserved, which might be of importance for the beneficial effect of this treatment in chronic renal disease.     

Genotyping of the CYP1A1 and GSTM1 genes in esophageal carcinoma patients with special reference to smoking

OBJECTIVES: Patients with cirrhosis and ascites have high plasma levels of atrial natriuretic peptide (ANP). Pharmacological doses of this hormone usually worsen systemic hemodynamics of cirrhotic patients. We assessed whether ANP influences cardiovascular homeostasis and renal function in patients with compensated cirrhosis at plasma levels comparable to those observed in patients with cirrhosis and ascites. METHODS: Radionuclide angiocardiography was performed in eight compensated cirrhotic patients during placebo (three periods of 15 min each) and ANP infusion (2, 4, and 6 pmol/kg.min for 15 min each), together with appropriate blood and urine sampling, to evaluate left ventricular diastolic, systolic, and stroke volume, heart rate, cardiac output, arterial pressure, peripheral vascular resistance, creatinine clearance, urinary sodium excretion, plasma renin activity, plasma aldosterone, norepinephrine and hematocrit. RESULTS: The infusion increased plasma ANP up to levels (52.03 +/- 2.29 pmol/L) comparable with those observed in 35 patients with ascites (46.42 +/- 1.57 pmol/ L). This increment was associated with significant reductions in left ventricular end diastolic volume, stroke volume, cardiac index (from 3.7 +/- 0.7 to 3.1 +/- 0.5 L/min.m2, p < 0.05) and mean arterial pressure (from 96.7 +/- 6.5 to 88.5 +/- 9.5 mmHg, p < 0.05), while heart rate and hematocrit significantly increased. Peripheral vascular resistance did not change. These hemodynamic effects occurred despite significant increases in plasma renin activity and norepinephrine. ANP also induced increases in creatinine clearance, urinary sodium excretion, and fractional sodium excretion. CONCLUSIONS: Low-dose ANP affected cardiovascular homeostasis and renal sodium handling in compensated cirrhosis, suggesting that this hormone may be involved in the pathophysiology of systemic hemodynamic and renal functional abnormalities of cirrhosis.     

Serum proinsulin in normal and gestational diabetic pregnancy

The tubular transport of urate and sodium was examined by clearance, free-flow micropuncture, intratubular microinjection and precession techniques in control rats and in rats receiving a new uricosuric diuretic, indanyloxyacetic acid (MK-196). The i.v. infusion of MK-196 (50 mg/kg of body wt/hr) resulted in significant increases in the fractional excretion of sodium (FENa) from 0.98 +/- 0.01 to 11.86 +/- 2.88% (P less than 0.001) and in FEurate from 14.1 +/- 1.03 to 56.0 +/- 2.86% (P less than 0.001). End-proximal tubular fluid to plasma inulin (TF/Pinulin) ratios were 2.43 +/- 0.15 and 2.51 +/- 0.10 in control and drug-treated animals, respectively (P = NS). Total urinary urate recovery after MK-196 administration was higher following microinjections of [2-14C] urate into early proximal tubule sites: 70.5 +/- 2.7% in controls vs. 84.9 +/- 0.9 (P less than 0.001), and after microinjections into late proximal tubule sites: 82.8 +/- 2.9% vs. 91.3 +/- 1.9 (P less than 0.05). Urinary precession of urate from inulin was demonstrable following placement of isotopes of these compounds on the surface of the kidney in controls, but was abolished by MK-196. This agent, therefore, inhibits the reabsorption and secretion of urate in the proximal convoluted tubule, the net effect being a marked increase in urinary urate excretion. By contrast, its inhibitory effect on sodium reabsorption is exerted at a site or sites distal to the accessible portion of the proximal tubule. The demonstration of reduced urate reabsorption and normal sodium reabsorption in the proximal tubule suggests that the reabsorption of these constituents of the glomerular filtrate is not intimately linked at this nephron site.     

Effect of substance P on proximal tubular reabsorption in the rat

Micropuncture and clearance techniques were used simultaneously to determine the effect of substance P on proximal tubular and overall renal function in anesthetized rats. This polypeptide, infused in saline at 50 pg/min into the abdominal aorta above the renal arteries, produced increases in urine flow, 2.7-3.7 mul/min.g kidney wt (P is less than 0.005); urinary sodium concentration, 32-61 meq/liter (P is less than 0.01); and sodium excretion, 89-223 neq/min (P is less than 0.005). Tubular fluid to plasma inulin concentration ratio measured in the last accessible proximal convolution fell from 2.21 to 1.80 (P is less than 0.001), and thus fractional reabsorption was reduced from 54 to 44% (P is less than 0.001). Absolute reabsorption by the proximal convoluted tubule was also reduced 15.5-12.5 nl/min (P is less than 0.025). In a control series of animals, saline alone infused at the same rate did not produce any statistically significant changes in the measured parameters over the same time period. The intrerenal mechanism responsible for the reduction in proximal reabsorption appears to be a tubular one since no consistent or significant changes were observed in kidney or single nephron glomerular filtration rate, renal plasma flow, or intrarenal hydrostatic pressures. No evidence was found to indicate redistribution of filtration rate, or plasma flow, or a reduction in filtration fraction.     

Renal water-electrolyte excretion and its control mechanisms. Current status of knowledge

The literature on hydronatriuresis control processes operating at the level of individual renal functional units and of the organ as a whole is analysed. 1) Elementary sodium salt and water tubular transport mechanisms. In converting the filtrate into urine, the kidney expends metabolic energy: this is used in the (active) transport of sodium salts; (passive) transport of water takes place along the osmotic gradients created by salt transfer. The proximal tubules reabsorb the sodium bic-rbonate actively. The reabsorption of the osmitic equivalent of water has the effect of concentrating NaCl in the tubular fluid. An important role in the reabsorption of NaCl is played by passive diffusion from the lumen to the interstitial fluid; the remainder is transferred actively, perhaps by an electrically neutral pump. With respect to the other nephronic segments, the proximal tubule has a relatively high passive permeability to water and salts: active transport here must not surmount high friction resistances nor take place against important concentration gradients. The low permeability of the distal nephron, on the other hand, increases the energy cost of salt transport; for the same reason, important electrochemical gradients are created and the composition of tubular fluid is drastically altered. 2) Elementary mechanisms of tubular potassium transport. Potassium is reabsorbed actively along the whole nephron by a luminal pump. The proximal tubules and Henle loops promote practically complete absorption of filtrated potassium. The distal tubules and collectors have the two-fold capacity of secreting and reabsorbing cation: the quantity of potassium excreted with the urine depends on the degree of excess of the secretion process. At distal tubular level, potassium secretion is a passive phenomenon dependent on the favourable transluminal gradient of the cation's electrochemical potential. 3) Renal function and volume homoeostasis of extracellular fluid. The organism's sodium content is largely controlled by renal excretion of sodium; homoeostasis of the sodium mass guarantees volume homoeostasis of the extracellular fluid through thirst and osmotic secretion of ADH. Extracellular fluid volume errors are picked up by the organism to the extent to which they translate themselves into pressure variations in the low pressure vascular system or into variations in haematic constituent concentration within the vascular sector, produced with velocities independent, at least in the short term, of the volume of extracellular fluid. In control of natriuria are the glomerular filtrate, intrarenal distribution of blood flow and tubular reabsorption of sodium; in its turn, the latter is subject to nervous and hormonal influences and influences from the physical environment surrounding the nephrons...     

Hypernatriuria and kaliuresis in enuretic children and the diurnal variation

PURPOSE: We investigate the underlying pathophysiological cause of primary nocturnal enuresis by comparing electrolyte alterations in urine samples of enuretics during the daytime and nighttime compared with those of nonenuretic subjects. MATERIALS AND METHODS: Urine output, urine specific gravity and urinary electrolytes in 15 enuretic and 12 nonenuretic children were measured. We collected daytime serum and urine samples of children fed a similar diet between 7 a.m. and 7 p.m., and nighttime between samples 7 p.m. and 7 a.m. Urinary calcium/creatinine ratio, tubular reabsorption of phosphorus and excretions of fractional sodium and potassium were calculated. RESULTS: There was no significant difference between the calcium/creatinine ratio ratios. There was a significant increase in fractional sodium and fractional potassium values in enuretics compared to nonenuretics during the day and at night. Daytime and nighttime fractional sodium and fractional potassium values in enuretics were similar. In contrast to nonenuretics, enuretic patients had no diurnal variation of fractional sodium. There was significant positive correlation between bedwetting status, and fractional sodium and fractional potassium. CONCLUSIONS: Since sodium and potassium excretions were higher in enuretic patients than nonenuretic children, and no significant diurnal variation in urinary excretion of these ions there might be a difference in the mechanism of reabsorption of sodium and potassium between enuretic and nonenuretic children.     

Effects of a nitric oxide synthesis inhibitor on renal sodium handling and diluting capacity in humans

BACKGROUND: Inhibition of nitric oxide (NO) synthesis has antinatriuretic and antidiuretic effects. Limited information is available on the role of NO in tubular sodium transport in the human kidney. METHODS: We studied nine healthy, sodium-replete males with clearance techniques during maximal diuresis. NG-monomethyl-L-arginine (L-NMMA, 3 mg/kg priming dose plus 3 mg/kg/h) was infused for 3 h, to achieve steady-state inhibition of NO synthesis. Data were compared with a time control study. RESULTS: The effects of L-NMMA were quickly established and persisted through the entire infusion period. Mean arterial pressure increased slightly from 85+/-3 to 91+/-3 mmHg (P<0.05). Renal plasma flow decreased substantially, and glomerular filtration rate slightly. Large decreases in absolute sodium excretion, from 79+/-10 to 34+/-5 micromol/min (P<0.01), and fractional sodium excretion, from 0.5+/-0.0 to 0.3+/-0.0% (P<0.01), were associated with significant reductions in fractional lithium excretion (P<0.05) and maximum urine flow (P<0.01). Minimal urine sodium concentration decreased from 5.8+/-0.04 to 3.9+/-0.4 mmol/l (P<0.01) whereas minimal urine osmolality increased (P<0.05). Plasma renin activity, aldosterone and atrial natriuretic peptide levels did not change, whereas urinary excretions of guanosine 3'5'-cyclic monophosphate and of nitrite plus nitrate decreased slightly. CONCLUSIONS: Inhibition of endogenous NO synthesis in humans to an extent that raises blood pressure only mildly causes antinatriuresis, that can be attributed to increases in sodium reabsorption both at proximal and distal nephron sites. In addition, renal diluting capacity decreases. The effects in the diluting segment have not been reported before, and may be due to medullary vasoconstriction, similar to that described for angiotensin II.     

Renal excretion of urate in mongrel and Dalmatian dogs: a micropuncture study

Free-low micropunction experiments were performed in mongrel dogs and in Dalmatian coach hounds infused with urate to obtain Purate levels of 0.15-0.21 mM before and during the infusion of pyrazinioc acid (PZA). In the absence of PZA, mongrel dogs excreted approximately 50% and Dalmatians 140% of filtered loads of urate. In mongrel dogs net reabsorption occurred only in the proximal convoluted tubules. PZA enhanced net proximal reabsorption and revealed the occurrence of proximal secretion, whereas fractional urate excretion in the urine decreased only slightly. In Dalmation dogs urate fluxes across walls of proximal convoluted tubules resulted in either net reabsorption or net secretion, with no mean change. Net urate secretion occurred between superficial late-proximal and early-distal tubules, and considerably decreased fractional excretion of urate. The renal handling of PZA was similar in mongrel and in Dalmatian dogs.     

Renal responses of the fetal lamb to fetal or maternal volume expansion

Fetal and maternal glomerular filtration rate (GFR), renal plasma flow (RPF), urine volume, sodium excretion, and fractional sodium reabsorption were measured in a chronically instrumented sheep preparation. Fetal GFR was essentially stable between 110 and 135 days of gestation (term = 147 days). There was a significant increase in GFR after 135 days. After the infusion of 50 ml of normal saline over a 30-minute period, fetal GFR and sodium excretion increased significantly. Fractional sodium reabsorption was significantly decreased. Thus, the fetus is capable of responding to volume expansion with saline with an increase in GFR and a decrease in fractional sodium reabsorption. After the infusion of 1000 ml of normal saline into the ewe in 1 hour, maternal GFR and RPF rose significantly. Sodium excretion rose 6-fold and fractional sodium reabsorption fell significantly. After the infusion of saline into the ewe, there was no change in fetal GFR, RPF, sodium excretion, urine volume, or fractional sodium reabsorption. Since there were no changes in fetal renal function after maternal volume expansion with saline there was no evidence for the transplacental passage of a natriuretic factor from ewe to fetus.     

Poisoning with methanol and ethylene glycol:1H NMR spectroscopy as an effective clinical tool for diagnosis and quantification

1. Renal haemodynamics, lithium and sodium clearance were measured in 14 patients treated with recombinant interleukin-2 for metastatic renal cell carcinoma. 2. Patients were studied before and after 72 h of continuous intravenous infusion of recombinant interleukin-2 (18x10(6) i.u..24 h-1.m-2) and 48 h post therapy. Cardiac output was measured by impedance cardiography. Effective renal plasma flow and glomerular filtration rate were determined by the renal clearances of 131I-hippuran and 99mTc-diethylenetriaminepenta-acetic acid (DTPA) respectively. Renal clearance of lithium (CLi) was used as an index of proximal tubular outflow. 3. Treatment caused a transient decrease in mean arterial blood pressure and systemic vascular resistance, but cardiac output remained unchanged. Renal blood flow decreased and renal vascular resistance increased during and after treatment. Sodium clearance decreased from 1.10 (0.63/1.19) ml/min to 0.17 (0.18/0.32) ml/min (P=0.003). Glomerular filtration rate remained unchanged, whereas the median CLi decreased from 26 (17/32) ml/min to 17 (10/21) ml/min (P=0.008). Calculated absolute proximal reabsorption rate of water increased from 63 (40/69) ml/min to 71 (47/82) ml/min (P=0.04). The urinary excretion rate of thromboxane B2 and the ratio between excretion rates of thromboxane B2 and 6-keto-prostaglandin-F1alpha increased by 98% (P=0.022) and 175% (P=0.022) respectively. 4. The study suggests a specific recombinant interleukin-2-induced renal vasoconstrictor effect. Changes in renal prostaglandin synthesis may contribute to the decrease in renal blood flow. The lithium clearance data suggest that an increased proximal tubular reabsorption rate may contribute to the decreased sodium clearance during recombinant interleukin-2 treatment.     

Micropuncture studies of glucose transport in the dog: mechanism of renal glycosuria

Clearance and micropuncture studies were performed in 23 dogs without glucose loading to examine the tubule mechanism of renal glycosuria. Studies were carried out in three groups of animals before and after 10% extracellular volume expansion, and administration of maleic acid in low dose at 150 mumol/kg and in high dose at 300 mumol/kg. Specific hexokinase methods were used for the determination of glucose in tubule fluid and urine. Under control conditios, glucose reabsorption occurred predominantly in the proximal tubule. In all three groups, proximal tubule reabsorption of both sodium and glucose was inhibited in the second phase, showing a good correlation between the two. In contrast, fractional urinary glucose excretion remained unchanged after volume expansion and low-dose maleic acid, indicating reabsorption of virtually all the increased glucose load at a further "distal" site. On the other hand, significant glycosuria developed after high-dose maleic acid that was a result of reduced glucose reabsorption in the distal nephron, in addition to the proximal effect. It was concluded that distal glucose transport plays a significant role in regulating urinary glucose excretion and maintains renal thershold for glucose,     

Urinary endothelin-like immunoreactivity in patients with cirrhosis

BACKGROUND/AIMS: To investigate a possible relationship between the renal production of endothelin and the presence of renal dysfunction and activation of vasoactive systems in cirrhosis, the urinary excretion and the circulating plasma levels of immunoreactive endothelin (irET) and the plasma levels of vasoactive hormones were measured in 19 healthy subjects, 12 cirrhotic patients without ascites and 39 patients with ascites and different degrees of renal dysfunction. METHODS: The urinary excretion and the circulating levels of irET were assessed after 5 days on a 40 mEq sodium diet and off diuretics. Renal function parameters and the plasma levels of vasoactive hormones were also measured. RESULTS: Patients with and without ascites had similar values of urinary irET as compared with healthy subjects (30+/-3, 31+/-3 and 29+/-2 ng/day, respectively, p>0.10). By contrast, patients with ascites had higher circulating levels of irET (15+/-1.2 pg/ml) than patients without ascites and healthy subjects (11+/-1.6 and 5+/-0.4 pg/ml, p<0.01). In patients with cirrhosis, no correlation was found between urinary irET and circulating irET. Moreover, urinary irET did not correlate with liver tests, serum and urine sodium, glomerular filtration rate or vasoactive substances. Patients with hepatorenal syndrome had similar urinary irET to patients with ascites without hepatorenal syndrome. CONCLUSIONS: Urinary excretion of irET is not increased in cirrhotic patients with ascites and does not correlate with abnormalities in renal function.     

The kidney in chronic liver disease: circulatory abnormalities, renal sodium handling and role of natriuretic peptides

Patients with chronic liver disease (L?ennec's cirrhosis) present sodium chloride retention, leading to fluid accumulation within the extracellular space (edema) and specially in the abdomen (ascites). This article reviews the pathogenesis of the hemodynamic abnormalities observed in these patients, particularly the hypothesis of "primary arterial vasodilation", with an increased nitric oxide production by endothelial cells playing a major role in the pathogenesis of vasodilation. Since excessive renal sodium reabsorption precedes ascites formation, two hypotheses are analyzed with respect to the handling of renal sodium in chronic liver disease: the underfilling and overflow theories. Furthermore, the role of natriuretic peptides is reviewed, the increment in atrial natriuretic peptide observed in well compensated cirrhotic patients being considered as a compensatory response to volume expansion, although with renal resistance to this peptide in early stages of the disease. This review ends with an integrated explanation of the circulatory disturbances, renal sodium retention and renal resistance to atrial natriuretic peptide resulting in the sodium and water abnormalities observed in chronic liver disease.     

A micropuncture study of the effect of parathyroid hormone on renal bicarbonate reabsorption

Renal micropuncture and clearance experiments were carried out in rats to study the effect of parathyroid hormone (PTH) on renal tubular HCO-/3 reabsorption. The rats were studied during an initial period of parathyroid deficiency (acute thyroidparathyroidectomy, TPTX) and during infusion of large amounts of bovine PTH. Under normal acid-base conditions, PTH administration to TPTX rats caused a significant rise in proximal tubular fluid HCO-/3 concentration (TFHCO-/3), a decrease in fluid reabsorption, and a fall in proximal HCO-/3 reabsorption from 94.0 to 88.2% (P less than 0.01). In control experiments with mannitol infusion, a comparable reduction in proximal fluid reabsorption occurred without any significant effect on intraluminal HCO-/3 concentration. During acute intravenous HCO-/3 loading, PTH inhibited proximal HCO-/3 reabsorption. However, no change in whole kidney HCO-/3 reabsorption was observed in these experiments or in the animals studied under normal acid-base conditions. The findings are consistent with the view that PTH inhibits proximal tubular HCO-/3 reabsorption with normal or high filtered loads of HCO-/3, but distal segments of the nephron are able to reabsorb the excess delivered from the proximal tubule. Measurements of urinary ammonium and titratable acid indicate that net acid excretion (NH+/4 + TA -- HCO-/3) increases significantly after PTH administration. These results do not provide support for the view that PTH excess causes metabolic acidosis by reducing renal acid excretion.     

Renal handling of Zn-alpha2-glycoprotein as compared with that of albumin and the retinol-binding protein

An unusual electrophoretic pattern of the urine from a patient with malignant lymphoma was observed. One of the major proteins, identified Zn-alpha2-glycoprotein (Zn-alpha2), was isolated from the urine and partly characterized. The Stokes radius was found to be 3.24 nm and the molecular weight, determined by sodium dodecyl sulfate polyacrylamide electrophoresis, 42,000. The plasma level in healthy individuals was 39 +/- 7 (SD) mg/liter. In 12 of 25 healthy individuals, Zn-alpha2 was measurable in the urine and was found to be 1.0 +/- 1.1 mg/liter. In 23 patients with chronic glomerulonephritis (CGN), in 9 with proximal tubular dysfunction (PTD), in 23 with various renal diseases (VRD), and in 10 with malignant lymphoma, the plasma level and the urinary excretion were compared with those of albumin (mol wt 67,000) and of the retinol-binding protein (RBP, mol wt 21,000). A close correlation was found between the urine-to-plasma (U/P) ratios of Zn-alpha2 and albumin in the patients with CGN, whereas in the PTD patients the U/P ratios of Zn-alpha2 and RBP were correlated. No significant renal arteriovenous difference in Zn-alpha2 could be demonstrated. The Zn-alpha2 excretion was increased also in two patients with malignant lymphoma and proteinuria of a tubular pattern. The plasma Zn-alpha2 varied inversely with the glomerular filtration rate in the patients with renal disease, but was normal in those with malignant lymphoma. The results are consistent with the assumption of a sieving coefficient of Zn-alpha2, substantially exceeding that of albumin, but notably lower than that of smaller low-molecular-weight proteins. An increased excretion of Zn-alpha2 may be due to increased glomerular permeability as well as to defective proximal tubular reabsorption.     

Influence of extracellular fluid volume expansion on magnesium, calcium and phosphate handling along the rat nephron

Renal tubular handling of P, Ca, Mg and Na was studied in the rat both before and during mild hypertonic NaCl loading (ECVE), using micropuncture and clearance techniques and electron microprobe analysis. Micropuncture was performed at the late proximal and early distal tubule sites. ECVE significantly increased the urinary output of all four elements. In the case of Mg, the increase was relatively small and depended on slight but statistically unsignificant inhibition of reabsorption all along the entire length of the nephron. For Ca, it depended on the inhibition of proximal reabsorption, partially compensated by increased reabsorption along the loop. For P, it depended on proximal inhibition, no important net phosphate movement occurring in the loop during both periods. Ca reabsorption was highly correlated to that of sodium along the proximal tubule and Henel's loop, Ca and Mg reabsorption were closely related to the load delivered at the beginning of the structure. These observations are compatible with the view that tubular reabsorption of Ca and Mg is concentration rather than Tm limited, and that reabsorption of Ca, unlike that of Mg, is linked to the movements of sodium. Following ECVE, the difference between early distal and urinary deliveries increased significantly for Ca and P, but not for Mg. For phosphate, this difference accounted for by 45% of the delivery at the early distal tubule site, at variance with microinjection data obtained in the rat under similar salt loading conditions, which indicated that 17% only of the phosphate distal delivery were reabsorbed along the terminal segments. This discrepancy is discussed in terms of nephron functional heterogeneity.