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.     

The effects of an angiotensin blocker (saralasin) on kidney function in dehydrated sheep

Saralasin, an angiotensin II analogue and receptor blocker, was infused at 7 and 15 micrograms . min-1 into dehydrated conscious Merino ewes. This caused mean arterial blood pressure, cardiac output, heart rate and renal vascular resistance to fall, and central venous pressure to rise. Renal plasma flow was unaffected but there were significant reductions in glomerular filtration rate, filtration fraction, urine flow, sodium and potassium excretion, solute clearance and solute-free water reabsorption. It is suggested that saralasin produced these effects by inhibiting endogenous angiotensin II activity, and in particular by causing a reduction in renal post-glomerular resistance. This in turn caused a fall in glomerular filtration rate and filtration fraction. While saralasin might have had effects on renal tubular function and perhaps on vasopressin secretion, the observed effects on renal function can be explained by the decrease in glomerular filtration rate and filtration fraction.     

Unique natriuretic properties of the ATP-sensitive K(+)-channel blocker glyburide in conscious rats

Small-conductance, ATP-sensitive K(+)-channels (KATP) localized in apical membranes of both thick ascending limb of the loop of Henle and cortical collecting duct cells may be involved in Na+ reabsorption and K+ secretion in the mammalian kidney. Possible pharmacologic tools to evaluate such an hypothesis may be the antidiabetic sulfonylureas which block K(+)-channels in pancreatic beta-cells. In saline-loaded conscious rats, glyburide (GLY) dose-dependently increased urinary Na+ excretion with little change in urinary K+ excretion after i.p. administration (10-100 mg/kg). In renal clearance studies, GLY at 25 mg/kg i.v. increased Na+ excretion 350% during the first hour post-treatment without affecting K+ excretion, glomerular filtration rate, mean arterial pressure or heart rate. GLY at 50 mg/kg was no more natriuretic than the 25 mg/kg dose, whereas 12.5 mg/kg of GLY increased Na+ excretion 200%. The change in Na+ excretion produced by 25 mg/kg of GLY in streptozotocin-induced diabetic rats was significantly greater than the change after drug vehicle in these animals. It is unlikely that the natriuresis produced by GLY is secondary to changes in plasma insulin and/or glucose because the doses used were far above GLY's insulin-releasing action (i.e., all natriuretic doses would have produced maximal insulin release) and GLY was natriuretic in streptozotocin-induced diabetic rats. It is possible that GLY interferes with reabsorption of Na+ by blocking KATP and thereby interrupting K+ recycling and Na(+)-2Cl(-)-K+ cotransport in the loop of Henle.     

Effect of furosemide on the transport of organic substances in the kidneys

The influence of furosemide on the maximal glucose reabsorption, cardiotrast secretion and urate excretion was studied in chronic experiment. Single injection of furosemide increased the maximal glucose reabsorption in dogs. Thesere was no alteration in the secretory cardiotrast transport in response to the drug administration. Furosemide administration produced an uricosuric action in dogs and rats.     

Duplex (thermotroph-psychrotroph) quadrant plates: convenient, error-avoiding tools for monitoring of HACCP-contained food lines and for epidemiological investigations under conditions of military or other constraints

The present study evaluated whether chronically administered low-dose (<5 mg/kg) ciclosporin A (CsA) affects renal haemodynamics and tubular function in renal transplant recipients (RTx) when studied at nadir CsA blood levels. The renal clearance of lithium was used as an index of proximal tubular outflow of sodium and water. Effective renal plasma flow, glomerular filtration rate, and renal clearance of lithium were studied in 67 stable non-diabetic RTx and 44 healthy controls. Forty-eight of the RTx were treated with CsA, prednisone, and azathioprine. Nineteen were treated exclusively with prednisone and azathioprine. In RTx with a good graft function (serum-creatinine <125 micromol/l), no specific CsA-induced renal haemodynamic and tubular dysfunctions were evident. In CsA-treated RTx with a slightly reduced renal function (serum creatinine 125-180 micromol/l) a decrease in fractional proximal tubular reabsorption was found. The renal clearances of urate and magnesium were comparable between RTx treated with or without CsA, and a significant correlation between glomerular filtration rate and renal clearance of urate was found. CsA-treated RTx had a significantly higher blood pressure, independent of glomerular filtration rate and segmental tubular function. In conclusion, at nadir CsA blood levels, no specific CsA-induced tubular dysfunction evaluated by the renal lithium clearance method could be demonstrated in RTx receiving chronically low-dose CsA. The hyperuricaemia commonly seen in RTx seems to be mainly caused by the reduced glomerular filtration rate.     

Renal function in cystic fibrosis with special reference to the renal sodium handling

Renal function was studied in 16 patients with cystic fibrosis, aged 5 to 19 years. The mean glomerular filtration rate and filtration fraction were increased compared to those in controls. Basal urinary sodium excretion as well as renal responses to oral and intravenous sodium loads were low, indicating an increased renal sodium reabsorption. Diluting capacity, measured as free water clearance, was decreased because of a low distal sodium delivery which might indicate an increased proximal sodium reabsorption.     

Trends in siting strategies

Renal function was measured by clearance technique before and after acute myocardial infarction (MI) induced by left coronary artery ligation in male Sprague-Dawley rats. The animals were anaesthetized with halothane-nitrous oxide, paralysed with pancuronium and artificially ventilated. All parameters were stable throughout the experiment in sham-operated time control animals (n = 8). After MI, rats developed left ventricular dysfunction with increased left ventricular end-diastolic pressure and decreased mean arterial pressure. MI produced antidiuresis and antinatriuresis without changes in glomerular filtration rate (GFR), lithium clearance or renal albumin excretion (n = 8). The antidiuretic and antinatriuretic responses to MI were similar in rats with chronic bilateral renal denervation (n = 5). Three additional rats with chronic bilateral renal denervation had cardiac arrest and were resuscitated with cardiac massage, i.v. lidocaine and intracardiac adrenaline administration. These animals showed a transient increase in urine flow rate, sodium and albumin excretion with maximum 30-60 min after resuscitation, while GFR and lithium clearance were normal. Since cardiac ischaemia and sympathetic stimulation are strong stimuli for the release of atrial natriuretic peptide (ANP), we examined if ANP (0.25, 0.50, and 1.00 microg kg(-1) min(-1), n = 8 per dose) affects urinary albumin excretion. ANP increased dose-dependently the urine/plasma concentration ratio of albumin relative to inulin, which suggests that ANP increases the glomerular permeability for albumin. We conclude that MI causes stimulation of renal tubular sodium and water reabsorption by a mechanism which is independent of intact renal innervation. MI does not produce any change in renal albumin excretion in rats, but transient albuminuria may be observed in rats following cardiac arrest and/or manoeuvres used in cardiac resuscitation. Since ANP produces albuminuria, we speculate that ANP may be an important mediator of albuminuria in states with elevated plasma concentrations of ANP.     

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.     

Significance of the karyopyknotic index in the course control of hormone-treated prostatic carcinoma

Renal function was evaluated in 40 patients with fulminant hepatic failure, They were divided into two groups on the basis of glomerular filtration rates greater than 40 ml/min or less than 25 ml/min. A number of patients in group 1 had markedly abnormal renal retention of sodium together with a reduced free water clearance and low potassium excretion which could be explained by increased proximal tubular reabsorption of sodium. The patients in group 2 had evidence that renal tubular integrity was maintained when the glomerular filtration rate was greater than or equal ml/min (functional renal failure), but evidence of tubular damage was present when this was less than 3 ml/min (acute tubular necrosis).     

Renal effects of guanabenz: a new antihypertensive

In order to determine the effects of guanabenz upon renal function, clearance studies were performed on hypertensive volunteers during sustained steady-state water diuresis. The data reveal an acute fall in renal hemodynamics and a marked reduction in sodium excretion during the 3rd and 4th hour after administration. Tha antinatriuresis was due to decreased filtration and enhanced distal nephron reabsorption of sodium, principally in association with secretion of potassium. Chronic administration of guanabenz for one week produced a sustained reduction in blood pressure, but there was no change in either body weight or 24-hour urinary sodium excretion. Repeat clearance studies revealed no change with either renal hemodynamics or sodium clearance. The data suggest that the acute antinatriuresis is a transient hemodynamic event and chronic therapy with guanabenz will not be complicated by sodium retention, a feature characteristic of other antihypertensive agents.     

The effect of indomethacin on renal function in pentobarbital-anesthetized dogs

The effects of indomethacin, an inhibitor of prostaglandin synthesis, on renal blood flow, glomerular filtration rate, urine flow and excretion of sodium and potassium were studied in the anesthetized dog. Indomethacin, 2.5 mg/kg i.v., decreased renal blood flow but increased aortic pressure and calculated renal vascular resistance. Glomerular filtration rate was not influenced by the synthetase inhibitor. Sodium excretion was decreased and para-aminohippurate extraction was increased after administration of indomethacin. Transient decreases in urine flow and potassium excretion were observed; however, both parameters returned to control value 75 minutes after administration of indomethacin. The early decrease in urine flow rate correlated closely with the decrease in sodium excretion. These data suggest that in the anesthetized dog, endogenous prostaglandins may serve to maintain renal blood flow but not glomerular filtration rate. Under the conditions of the present experiments, sodium excretion and to a lesser extent potassium excretion have been suggested as being dependent on prostaglandin synthesis.     

Mechanism of increased renal clearnace of amylase/creatinine in acute pancreatitis

We investigated three possible causes of the increased ratio of amylase/creatinine clearance observed in acute pancreatitis. The presence of rapidly cleared isoamylase was excluded by studies of serum and urine, which demonstrated no anomalous isoamylases. In pancreatitis, the ratios (+/-1 S.E.M.) of both pancreatic isoamylase (9.2+/-0.6 per cent) and salivary isoamylase (8.6+/-1.6 per cent) were significantly (P less than 0.01) elevated over respective control values (2.4+/-0.2 and 1.8+/-0.2 per cent). Increased glomerular permeability to amylase was excluded by the demonstration of normal renal clearance of dextrans. We tested tubular reabsorption of protein by measuring the renal clearance of beta2-microglobulin, which is relatively freely filtered at the glomerulus and then avidly reabsorbed by the normal tubule. During acute pancreatitis the ratio of the renal clearance of beta2-microglobulin to that of creatinine was 1.22+/-0.52 per cent, an 80-fold increase over normal (0.015+/-0.002 per cent), with a rapid return toward normal during convalescence. Presumably, this reversible renal tubular defect also reduces amylase reabsorption and accounts for the elevated renal clearance of amylase/creatinine observed in acute pancreatitis.     

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.     

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.     

Glucose and bicarbonate reabsorption in edematous dogs

Glucose and bicarbonate reabsorption were studied in dogs made edematour by aortocaval fistula (A-V dogs) and in sham-operated dogs. Following construction of the A-V fistula, there was a significant increase in body weight; glomerular filtration rate, renal plasma flow, hematocrit, and sodium excretion decreased significantly. Bicarbonate reabosorption was significantly higher in A-V than in sham dogs both during control and volume expansion. Volume expansion depressed bicarbonate reabsorption significantly in both groups. Glucose reabsorption fell following volume expansion in both groups; glucose reabsorption was significantly higher in A-V dogs than in sham dogs during control and volume expansion. Volume expansion led to a minimal increase in sodium excretion in A-V dogs when compared to the increase in the sham dogs. These data demonsttate that chronic sodium retention is associated with enhanced reabsorption of glucose and bicarbonate. The site in the neophron responsible for the increase in reabsorption of these substances cannot be determined with certainty based on these clearance studies although it is possible that proximal reabsorption may be enhanced in this model.     

Renal function as a marker of human fetal maturation

Sixty clinically well infants of various gestational ages (27 to 40 weeks) were studied from 24-40 hours after birth to evaluate glomerular filtration rate and renal excretion rate of sodium at various stages of fetal maturation. Creatinine clearance was directly related to gestational as (r = 0.643). Fractional sodium excretion was inversely related to gestational age (r = -0.755). The renal functions of small for gestational age infants were similar to those of full-term infants whose birth weights were appropriate for gestational age. The data showed that the glomerular functions of an infant below 32 weeks of gestation were more predominant than the tubular function resulting in a greater fractional sodium excretion rate and higher urinary Na loss in infants of this gestational age, when compared with the more mature infants.     

An oral glutamine load enhances renal acid secretion and function

In a recent study, a small oral glutamine load acutely elevated plasma bicarbonate concentrations in healthy adults (Am J Nutr 1995;61:1058-61). The present study was designed to elucidate the renal mechanism underlying the base-generating response to L-glutamine. Accordingly, vehicle (489 mL diet soda) or vehicle plus 2 g L-glutamine (28 mg/kg body wt) was ingested and the gain in extracellular fluid volume bicarbonate was compared with renal acid elimination as either ammonium excretion or tubular acid secretion (titratable acid plus bicarbonate reabsorption). Vehicle alone, which contained 27 mmol acid, did not increase extracellular fluid volume bicarbonate over the 90-min period. In contrast, L-glutamine increased plasma bicarbonate concentration (from 25.4+/-2 to 27.9+/-1 mmol/L, P < 0.05) and extracellular fluid volume bicarbonate by an estimated 39+/-10 mmol. When added to that required to neutralize the ingested acid, the combined total for new bicarbonate generated gave an estimated 66+/-10 mmol. Surprisingly, ammonium excretion accounted for < 2% of this newly generated bicarbonate. However, acid secreted and excreted as net acid (5.2+/-4.0 mmol/90 min) as well as that coupled to enhanced bicarbonate reabsorption (76+/-20 mmol/90 min) readily accounted for the estimated base gain (81+/-24 compared with 66+/-10 mmol/90 min). Concomitant with enhanced renal acid secretion, the oral glutamine load elicited an increase in glomerular filtration rate. These results rule out a role for L-glutamine as a direct precursor of bicarbonate and instead point to an indirect role in accelerating acid secretion, apparently coupled to increased glomerular filtration rate.     

Parathyroid hormone and renal excretion of phosphate and calcium in normal starlings

The renal handling of calcium, phosphate, sodium, and potassium was studied in normal and parathyroid extract (PTE)-injected starlings, Sturnus vulgaris. The birds were anesthetized with Equi-Thesin and infused intravenously with 2.5% mannitol containing [14C]inulin. Normal starlings actively reabsorb all four of these substances. After intravenous administration of 50 IU PTE/100 g body wt, the relative phosphate clearance (CPO4/CIn) as well as tubular transfer of phosphate (TPO4) increased significantly. Phosphate secretion occurred and usually persisted longer than 2 h. The relative calcium clearance also rose after PTE, but the TCa did not shift. This probably indicates that the tubular transport maximum (Tm) for calcium had been exceeded. The relative clearances of sodium and potassium also increased after PTE; however, only the rise in CNa/CIn was significantly different from the controls. The glomerular filtration rate (CIn) also increased significantly after PTE, but this effect was transient and cannot explain the longer lasting effects of PTE on excretion of phosphate, calcium, or sodium.     

Antibacterial activity of the derivatives of cholic acid (author''s transl)

Serum and urinary myo-inositol and urinary glucose were estimated by means of gas-liquid chromatography in 54 patients with glomerulonephritis with and without renal failure. myo-Inositol clearance was calculated and an index was formulated which reflected changes in glomerular filtration, tubular reabsorption and catabolism of myo-inositol by the kidney. Serum and urinary myo-inositol levels were increased in glomerulonephritis with a close correlation to the degree of renal failure. In advanced forms of glomerulonephritis, glomerular filtration, tubular reabsorption and catabolism of myo-inositol were shown to be markedly deranged. Evidence obtained showed further that a derangement of tubular reabsorption and catabolism of myo-inositol also accompany milder forms of glomerulonephritis without decreased glomerular filtration. The myo-inositol index value, especially, was increased in patients with signs of disease activity as indicated by a histological examination of the kidney tissue. The index can also be regarded as a highly sensitive test of renal failure. Low grade glucosuria was shown to be frequently associated with glomerulonephritis with renal failure. Evidence was produced which suggested that the tubular reabsorption of myo-inositol was deranged earlier than glucose reabsorption in glomerulonephritis, although they may share a common step in the reabsorption process. The data suggest that the estimation of serum and urinary myo-inositol has advantages in the evaluation of kidney function.     

Low dose angiotensin converting enzyme inhibition and glomerular permselectivity in renal transplant recipients

In this study, we determined the fractional clearance of neutral polydisperse dextrans (theta D) and monodisperse dextran sulfate (theta DS) to describe glomerular size and charge selectivity in 25 renal transplant recipients with proteinuria. Thirteen were treated with low dose lisinopril for six months (group 1) and 12 patients without ACE inhibitor therapy formed group 2. Mean arterial blood pressure was stable (group 1, 112 +/- 4; group 2, 109 +/- 2 mm Hg at baseline and after 6 months) whereas creatinine clearance, glomerular filtration rate and renal plasma flow decreased nonsignificantly but were comparable at any time. Lisinopril treatment lowered filtration fraction (22 +/- 2 vs. 19 +/- 2%, P = 0.07) whereas no change was seen in group 2 (20 +/- 2%). The fractional protein excretion (mg urinary protein per day/ml creatinine clearance per day) was stable in group 1, but significantly increased in group 2. The same pattern was found for theta D larger than 56 A. theta DS was stable and consistently elevated in both groups at any time. We conclude that low dose ACE inhibitor treatment in proteinuric renal transplant recipients stabilizes glomerular size selectivity independently of its systemic hemodynamic effects.