Effect of somatostatin on kidney function and vasoactive hormone systems in healthy subjects

Summary The acute effects of i.v. somatostatin (250 mcg bolus followed by 250 mcg/h continuous infusion for two hours) on renal hemodynamics, renal electrolyte and water handling, and urinary excretion of catecholamines and prostaglandins, as well as on plasma concentrations of arginine vasopressin, atrial natriuretic factor, norepinephrine, epinephrine, dopamine, glucagon, and plasma renin activity were studied in seven normal subjects. Somatostatin decreased effective renal plasma flow and glomerular filtration rate, osmotic and free water clearances, urine volume, and sodium and potassium excretion, while urinary osmolality, fractional excretion of sodium, and phosphate excretion increased significantly. Plasma concentrations of arginine vasopressin, atrial natriuretic factor, norepinephrine, epinephrine, and dopamine remained unchanged, while plasma renin activity (3.0±0.25 vs 2.4±0.2 ng AngI/ml/h;p}<0.01) and glucagon levels (40±11 vs 20±16 pg/ml;p}<0.01) decreased. Urinary excretion of norepinephrine, epinephrine, dopamine, PGE₂, and PGF_2alpha was suppressed under somatostatin. A significant positive correlation was found between urinary dopamine and sodium excretion (r=0.7;p}<0.001) and urinary postaglandin E₂ and glomerular filtration (r=0.52;p}<0.01). Without accompanying changes in plasma osmolality and vasopressin concentration significant antidiuresis occurred, suggesting a direct tubular effect of somatostatin. However, the hormone-induced changes are due mainly to the decrease in renal plasma flow. The results demonstrate that somatostatin at supraphysiological doses exerts significant effects on the kidney.Abbreviations PAH paraaminohippuric acid - ANF atrial natriuretic factor - AVP arginine vasopressin - PRA plasma renin activity - ERPF effective renal plasma flow - GFR glomerular filtration rate - TRP tubular reabsorption of phosphate - NE norepinephrine - E epinephrine - DA dopamine - GH growth hormone     

Effect of Renal Insufficiency on Stone Recurrence in Patients with Urolithiasis

The study was designed to assess the relationship between glomerular filtration rate (GFR) and urinary stone-forming constituents, and to assess the effect of renal insufficiency on stone recurrence risk in first stone formers (SF). Baseline serum creatinine levels were obtained, and renal insufficiency was defined as creatinine clearance ≤60 mL/min (Cockroft-Gault). This retrospective case-control study consists of 342 first SF; 171 SF with normal renal function were selected with 1:1 propensity scores matched to 171 SF with renal insufficiency. Urinary metabolic evaluation was compared to renal function. GFR was positively correlated with urinary calcium, uric acid, and citrate excretion. Subjects with renal insufficiency had significantly lower urinary calcium, uric acid, and citrate excretion than those with normal renal function, but not urine volume. With regard to urinary metabolic abnormalities, similar results were obtained. SF with renal insufficiency had lower calcium oxalate supersaturation indexes and stone recurrence rates than SF with normal renal function. Kaplan-Meier curves showed similar results. In conclusion, GFR correlates positively with urinary excretion of stone-forming constituents in SF. This finding implies that renal insufficiency is not a risk factor for stone recurrence.

Graphical Abstract

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Dissociation between antidiuretic response and renal medullary cyclic AMP levels in the rat

Renal tubular bicarbonate reabsorption and acidification were evaluated in phosphate depleted rats (PD) and controls. After 33 days of phosphate depletion, urine pH of PD rats (N=5, 6.36±0.15) was significantly higher than control (N=5, 5.64±0.09,P<0.005) following an NH₄Cl load. Urinary titratable acid of PD rats (9.6±1.8) was significantly reduced compared to control (117.2±19.7 Eq/3 h,P<0.001), whereas NH ₄ ⁺ excretion was not different. The plasma HCO ₃ ^– thresholds at which bicarbonaturia occurred (approximately 25 mEq/l) were identical in controls and phosphate depleted rats during isotonic bicarbonate infusion. The higher urine pH of phosphate depleted rats following NH₄Cl administration was not due to low urinary phosphate as 3-day phosphate depleted rats could normally acidify urine after NH₄Cl (pH=5.86±0.09,N=6 vs. control 5.87±0.08,N=6,P=N.S.) despite urinary phosphate excretion as low as in 33-day PD rats. These data indicate the presence of impaired distal tubular acidification in chronically phosphate depleted rats.Former trainee of the Cardiovascular Research Program and currently a third year medical student at The University of Michigan Medical School.     

Acute uric acid nephropathy in two gouty patients with moderate hyperuricemia and high urine acidity

Summary Acute uric acid nephropathy has been described almost uniformly in patients with massive uric acid overload (malignancies with rapid cell destruction, epileptic seizures). Severe hyperuricosuria and intratubular uric acid precipitation result. Here we present two patients with gout, normal uric acid production, and moderate hyperuricemia, both of whom developed acute uric acid nephropathy. Because of pronounced urine acidity (pH values of 4.6 and 5.0 in morning fasting urines), supersaturation with respect to undissociated uric acid exceeded solubility (0.54 mmol/l), despite basal urate secretions of less than 2.2 mmol/24 hours. Additional predisposing factors, such as uricosuric treatment, heavy beer-drinking, over-consumption of purine-rich foods, and hot environment, were superimposed in both cases.Abbreviations S_Cr serum creatinine - S_UA serum uric acid - GFR glomerular filtration rate - C_Cr creatinine clearance - C_Urate urate clearance - UV_Urate urinary excretion of urate - UUA urinary undissociated uric acid - TUA urinary total uric acid - FE_Urate fractional excretion of urate     

Is magnesium a marker of disordered mineral metabolism in males with idiopathic recurrent calcium urolithiasis? Observations focussing on fasting magnesiuria and magnesiemia, protein and other substances in urine and plasma.

Mg can theoretically play a role in renal calcium stone formation of IRCU patients, but the status of Mg is uncertain. The aim of this study was to investigate whether in IRCU variation of Mg in fasting urine and plasma is associated with altered urine Ca, Pi, oxalate, Ca/Pi ratio, supersaturation and other factors, the clinical severity of stone disease (metabolic activity; MA) included. This was a cross-sectional study (284 IRCU patients), comprising males with mean age in the fifth decade and unimpaired renal function. Patients had an unrestricted home diet, standardized laboratory procedures, including sample collection (daily and fasting urine, plasma), with classification of patients according to tertiles of fasting Mg-uria, keeping comparable age, the number of patients with renal stones present or absent, and normo- or idiopathic hypercalciuria. MA was scored. We found that the tertile I patients (= referent) exhibited sub-normal fasting Mg excretion (< 4 mg/2 h) and fractional excretion (< 3.5%), in daily urine the lowest Mg and oxalate, but highest Ca excretion rate; compared with tertile III, tertile I patients had significantly lower plasma total (not ultrafiltrable) Mg, blood bicarbonate and pH, and the lowest MA; fasting urinary excretion of Ca and citrate were also low, but urinary Pi, body weight, plasma glucose and insulin were increased. In tertile III not only was Mg-uria (excretion, FE) significantly elevated vs I, but so were urinary pH, excretion of sodium, Ca, potassium, protein (total and non-albumin) and citrate, FE sodium and Ca, the urinary molar ratios Ca/Pi and Mg/Potassium, hydroxyapatite supersaturation, bone resorption markers, and MA; in this environment urinary oxalate and Ca oxalate supersaturation were unchanged, plasma glucose, insulin and parathyroid hormone decreased. The tertile II patients, showing intermediate Mg excretion, also exhibited (vs. I) increase of FE Mg, urinary excretion and FE of sodium and Ca, excretion of protein, citrate and bone markers, the ratios Ca/Pi and Mg/Potassium, and MA. When urinary Ca/Pi was considered as the outcome of disordered metabolism, significant determinants (according to multiple regression analysis) were urinary Pi (negative), Ca and Mg/Potassium (positive); significant determinants of MA, the sum of stone-forming processes, were the urinary concentration of non-albumin protein, Mg/Potassium and sodium (all positive). Among IRCU patients 1) approx. one third is in need of Mg conservation by the kidney, associated with low plasma total Mg, modest metabolic acidosis, a trend towards overweight, high plasma insulin and glucose; 2) low Mg- or acidosis-induced increase of bone resorption may follow, attenuating glycemia and insulinemia but forcing the kidney to functional adaptation, manifesting as a rise of urinary sodium, Mg, Ca, Pi, Ca/Pi, pH and protein, together presumably aggravating MA; 3) larger controlled studies are justified, to decide whether Mg deficiency initiates renal Ca stones, and if urinary Mg loss exaggerates IRCU.     

Kinetic parameters of calcium metabolism and femur morphometry in rats

The aim of this study was to establish the influence of age and sex on the kinetic and morphometric parameters of calcium metabolism. Normal values of kinetic parameters were determined in normal adult rats of different ages (4–20 months) and both sexes. Urinary hydrophyline excretion was also assessed and morphometric measurements of the femur were performed.Kinetic parameters expressed as rate constants showed a lowering of calcium turnover (k _T) in the rapidly exchangeable calcium compartment until the age of 12 months and urinary and fecal rate constants (k _u andk _f ) showed a small increase. Males exhibited a lower calcium turnover (k _T) as well as lower urinary and fecal rate constants. Hydroxyproline excretion diminished with age in both sexes. Lower values were recorded in males. Morphometric parameters of femurs showed no bone loss within the examined age. The results show that differences between the sexes exist in the sense of a faster calcium turnover, higher calcium excretion rate constants, higher collagen degradation and higher bone density in adult female rats.List of symbols P rapidly exchanging pool - E slowly exchanging pool - V _e rate of exchange between P and E - V _T total loss from P in unite time - V ₀₊ rate of accretion to bone - V _u rate of excretion in urine - V _f rate of endogenous fecal excretion - R _u ] ₀ ⁷² total activity excreted in urine between zero and 72 h - R _f ] ₆ ⁵⁴ total activity excreted in feces between 6 and 54h - R _s plasma specific activity This work was partially supported by a research grant from the U.S. Department of Agriculture, Beltsville, Maryland.     

Inactivation of urinary kallikrein by alpha1-antitrypsin

Summary Proteolytic activity, with azocasein as substrate in the presence and absence of 0.4 IU kallikrein (Padutin) was measured in the 24 h urine fractions of 100 ambulatory patients with hypertension, proteinuria or haematuria. Urinary protein and alpha₁-antitrypsin concentration have also been assayed. There was an inverse relationship between kallikrein activity and urinary alpha₁-antitrypsin concentration (r=0.84;y=39.2e ^–0.009x). Furthermore, kallikrein activity and 24 h urinary alpha₁-antitrypsin excretion were also inversely correlated (r=0.81;y=886.4e ^–0.011x). Our data suggest an inactivation of renal kallikrein by urinary alpha₁-antitrypsin.This work was supported by the Deutsche Forschungsgemeinschaft (Ho 781/3-2)     

Long-term elevations of dietary sodium produce parallel increases in the renal excretion of urodilatin and sodium

The effects of dietary sodium intake on the renal excretion of urodilatin and of sodium were examined in six healthy male subjects. The 24-day study period was divided into three phases of 8 days each. Subjects Ingested 2.8 mequiv sodium (kg body weight)^–1 day^–1 during the first phase, 5.6 mequiv (kg body weight)^–1 day^–1 during the second phase, and 8.4 mequiv (kg body weight)^–1 day^–1 during the third phase. The excretion of both sodium (P<0.002) and urodilatin (P<0.006) increased in response to the increasing dietary sodium, while urine flow did not change. Urinary urodilatin excretion correlated closely with renal sodium excretion (P<0.001). Serum aldosterone levels (P<0.01) as well as serum renin levels (P<0.05) significantly decreased with increasing sodium intake. Plasma [Arg]vasopressin levels increased significantly (P<0.05). Plasma atrial natriuretic factor and cGMP levels as well as urinary cGMP excretion rates were unaltered by the changes in sodium intake. We conclude from these results that the renal natriuretic peptide, urodilatin, but not the main cardiac member of the natriuretic peptide family may be involved in the regulation of day-to-day sodium balance.     

Gain-of-function haplotype in the epithelial calcium channel TRPV6 is a risk factor for renal calcium stone formation

The rate-limiting step of dietary calcium absorption in the intestine requires the brush border calcium entry channel TRPV6. The TRPV6 gene was completely sequenced in 170 renal calcium stone patients. The frequency of an ancestral TRPV6 haplotype consisting of three non-synonymous polymorphisms (C157R, M378V, M681T) was significantly higher (P = 0.039) in calcium stone formers (8.4%; derived = 502, ancestral = 46) compared to non-stone-forming individuals (5.4%; derived = 645, ancestral = 37). Mineral metabolism was investigated on four different calcium regimens: (i) free-choice diet, (ii) low calcium diet, (iii) fasting and (iv) after a 1 g oral calcium load. When patients homozygous for the derived haplotype were compared with heterozygous patients, no differences were found with respect to the plasma concentrations of 1,25-vitamin D, PTH and calcium, and the urinary excretion of calcium. In one stone-forming patient, the ancestral haplotype was found to be homozygous. This patient had absorptive hypercalciuria. We therefore expressed the ancestral protein (157R+378V+681T) in Xenopus oocytes and found a significantly enhanced calcium permeability when tested by a (45)Ca(2+) uptake assay (7.11 +/- 1.93 versus 3.61 +/- 1.01 pmol/min/oocyte for ancestral versus derived haplotype, P < 0.01). These results suggest that the ancestral gain-of-function haplotype in TRPV6 plays a role in calcium stone formation in certain forms of absorptive hypercalciuria.     

Indices of mineral metabolism in relation to blood pressure in a sample of a healthy population

Indices of mineral metabolism in blood and urine were analysed in relation to blood pressure in 97 healthy subjects aged 16-82 years. In a multivariate analysis, after allowing for the effects of sex, body mass index (BMI) and age, there was an inverse relationship between plasma level of ionized calcium and mean blood pressure (MBP) (beta = -50.0 mmHg/mmol/l P-ionized calcium, p = 0.0005). In univariate analyses MBP also showed statistically significant inverse relationships with plasma ionized calcium, serum phosphate and renal threshold concentration of phosphate; positive relationships to MBP were found for fasting urinary excretion of calcium and cyclic adenosine monophosphate. However, when examined multivariately, only the relation between MBP and plasma ionized calcium persisted. This study supports previous findings of an inverse relationship between blood pressure and serum ionized calcium and extends the observations to the physiological range. It is further evident from this study that BMI and age should be taken into account in analyses of the relationship between blood pressure and mineral metabolism.     

Effects of orally administered glandular kallikrein on urinary kallikrein and prostaglandin excretion,plasma immunoreactive prostanoids and platelet aggregation in essential hypertension

Summary The effects of orally administered glandular kallikrein on urinary kallikrein, aldosterone and prostaglandin E (PGE) excretion, plasma renin activity (PRA), immunoreactive 6-keto PGF₁ and thromboxane B₂ concentrations and platelet aggregation were studied in 12 patients with essential hypertension (EH). After a 2-week control period, each patient was given orally 450 KU/day of hog glandular kallikrein for 8 weeks. Urinary kallikrein, aldosterone and PGE excretion, and plasma 6-keto PGF₁ and thromboxane B₂ concentrations were measured by radio-immunoassay. Platelet aggregation was measured by the addition of ADP, collagen or ristocetin with an aggregometer. Urinary kallikrein excretion and plasma 6-keto PGF₁ concentration were significantly decreased in patients with EH. There were no significant differences in PRA, urinary aldosterone excretion and plasma thromboxane B₂ concentrations between control subjects and patients with EH. There was a significant decrease in blood pressure in patients with EH coinciding with significant increases of urinary kallikrein and PGE excretion and plasma immunoreactive 6-keto PGF₁ concentration after administration of glandular kallikrein. There was also a significant inhibition of platelet aggregation induced by collagen in these patients. Thus, a suppression of the kallikrein-kinin-prostaglandin system in patients with EH was found, and a decrease in blood pressure with an increment of urinary kallikrein, PGE excretion, plasma immunoreactive 6-keto PGF₁ and inhibition of platelet aggregation in vivo by the administration of glandular kallikrein.Abbreviations BK bradikinin - EH essential hypertension - KU kallikrein unit - PG prostaglandin - PRA plasma renin activity - PRP platelet rich plasma - TX thromboxane Presented at IXth European Congress of Cardiology Düsseldorf, July 8–12, 1984     

Impaired ability to increase water excretion in mice lacking the taurine transporter gene TAUT

Summary Cellular taurine uptake or release counteracts alterations of cell volume. Na⁺-coupled taurine transporter TAUT mediates concentrative cellular uptake of taurine. Inhibition of vasopressin secretion by hypotonicity may involve taurine release from glial cells of supraoptic nucleus. We compared renal function of mice lacking TAUT (taut^–/–) and wild-type littermates (taut^+/+). We observed renal taurine loss and subsequent hypotaurinemia in taut^–/– mice. With free access to water, plasma and urine osmolality, urinary flow rate as well as urinary excretion and plasma concentrations of Na⁺ and K⁺ were similar in taut^–/– and taut^+/+ mice, whereas plasma concentrations of urea were enhanced in taut^–/– mice. An oral water load (1 ml/16 g body weight) induced a similar diuresis in both genotypes. Repeating the oral water load immediately after normalization of urine flow rate, however, resulted in delayed diuresis and higher urinary vasopressin/creatinine ratios in taut^–/– mice. In comparison, the repeated diuretic response to vasopressin V₂ receptor blockade was not different between genotypes. Water deprivation for 36 h led to similar antidiuresis and increases of urinary osmolality in both genotypes. Upon free access to water after deprivation, taut^–/– mice continued to concentrate urine up to 6 days, while taut^+/+ mice rapidly returned to normal urinary osmolality. Urinary vasopressin/creatinine ratios and plasma aldosterone concentrations were not different under basal conditions but were significantly higher in taut^–/– mice than in taut^+/+ mice at 6 days after water deprivation. In conclusion, taut^–/– mice suffer from renal taurine loss and impaired ability to lower urine osmolality and to increase urinary water excretion. The latter defect could reside extrarenally and result from a role of taurine in the suppression of vasopressin release which may be attenuated in taut^–/– mice.     

Role of 1,25-Dihydroxy Vitamin D3 and Parathyroid Hormone in Urinary Calcium Excretion in Calcium Stone Formers

Purpose

To find out the possible role of 1,25(OH)₂ vitamin D₃ [1,25(OH)₂D₃] and parathyroid hormone (PTH) as intrinsic factors in urinary calcium stone formers (SFs), we investigated their relationship with serum and urinary biochemical parameters.

Materials and Methods

A total of 326 calcium SFs (male: 204, female: 122) were enrolled and underwent outpatient metabolic evaluations including 1,25(OH)₂D₃ and PTH as well as serum and 24-hour urinary biochemical parameters. As control, 163 age- and sex-matched (2:1) individuals (non-SFs) who have never urinary stone episode were included.

Results

1,25(OH)₂D₃ level was positively correlated with urinary calcium excretion (r=0.347, p<0.001). The hypercalciuric group and recurrent SFs had higher serum 1,25(OH)₂D₃ levels than the normocalciuric group (p<0.001) and first SFs (p=0.050). In the adjusted multiple linear regression analysis, serum 1,25(OH)₂D₃ level (β=0.259, p<0.001) and serum PTH level (β=-0.160, p<0.001) were significantly correlated with urinary calcium excretion. The patients in highest tertile of 1,25(OH)₂D₃ had a more than 3.1 fold risk of hypercalciuria than those in the lowest tertile (odds ratio=3.14, 95% confidence interval: 1.431-6.888, p=0.004). No correlation was observed between PTH and 1,25(OH)₂D₃ (R=0.005, p=0.929) in calcium SFs, while a negative correlation was found in controls (R=-0.269, p=0.001).

Conclusion

1,25(OH)₂D₃ was closely correlated with urinary calcium excretion, and high 1,25(OH)₂D₃ levels were detected in the hypercalciuric group and in recurrent SFs. However, 1,25(OH)₂D₃ was not correlated with PTH in calcium SFs. These findings suggest that 1,25(OH)₂D₃ might be important intrinsic factor for altered calcium regulation in SFs.     

X-ray microanalysis of spontaneously formed urinary calculi in a jaundiced strain of rat

A high incidence of spontaneously formed urinary stone was found in the females of a jaundiced strain of rat developed from a cross between Gunn's rat and Wistar-Imamichi rat. In this colony, 42.3% of the females had urinary calculi. Elemental analyses of these urinary calculi were carried out with an analytical electron microscope, a high-resolution transmission electron microscope fitted with an energy dispersive type X-ray microanalyzer and a scanning device. In the surface and middle areas of the stone, the main components were recognized as magnesium (Mg) and phosphorus (P). In the central region of the stone, calcium (Ca) and phosphorus (P) were found as the main elements with trace amounts of sodium (Na), chlorine (Cl), and potassium (K). The analyses indicated that the spontaneous urinary stone consisted of phosphate salts with calcium or magnesium. In addition, the mass ratio of the $\text{Mg}\text{P}$ or $\text{Ca}\text{P}$ in the stones was calculated from X-ray pulse intensity ratios and compared with the mass ratio of a standard sample. The results suggested that the magnesium and phosphorus in the urinary stones existed as ammonium magnesium phosphate, MgNH₄PO₄, and the calcium and phosphorus as tribasic calcium phosphate, Ca₃(PO₄)₂.     

Acute renal failure due to uric acid nephropathy in a patient with renal hypouricemia

Summary This report is about a 23-year-old man who required hemodialysis in connection with an acute renal failure resulting from uric acid nephropathy without hyperuricemia. After recovering renal function he showed extreme hypouricemia (0,1–0,3 mg/dl) and elevated uric acid clearance (100–300 ml/min). The fractional excretion of uric acid (Cua/Cer) could be suppressed by oral pyrazinamide and enhanced by probenecid. As no other renal tubular or metabolic abnormalities were detected, it is suggested that a markedly increased renal tubular urate secretion was responsible for the hypouricemia and also for the rare side-effect of an uric acid nephropathy in this patient.Abbreviations PZA pyrazinamide - GFR glomerular filtration rate - S_UA serum uric acid - UV_UA urinary excretion of uric acid - C_UA uric acid clearance - C_CR creatinine clearance     

Atrial pressure and postprandial volume regulation in conscious dogs

Conscious, chronically instrumented dogs (n=24; left and right atrial catheter, electromagnetic flow probe around the left renal artery, carotid loop) were used in 97 expts. to study mechanisms mediating postprandial (pp) excretion of sodium and water up to at least 180 min after food intake. The dogs were kept under standardized conditions and maintained on ahigh (14.5 mmol Na/kg b.w./day) or alow (0.5 mmol Na/kg b.w./day) sodium intake diet (HSI, LSI) which was given once daily in the morning.In HSI dogs left atrial pressure (LAP) increased from a fasting control value of 0.2 kPa (2 cm H₂O) to 0.7 kPa (7 cm H₂O) (120–180 min pp), right atrial pressure from 0.0 kPa (0 cm H₂O) to 0.3 kPa (3 cm H₂O). 25% of the sodium intake were excreted up to 180 min pp. There was a highly significant positive correlation between pp sodium excretion (U _Na V) and pp LAP.U _Na V was not related to pp increase in renal blood flow (RBF) and glomerular filtration rate (GFR). Fractional sodium excretion increased from a fasting control value of 0.6% to more than 4% in HSI dogs and from 3.3% to more than 7% in anadrenalectomized HSI dog. DOCA did not diminishU _NA V in HSI dogs.In LSI dogs, RBF and GFR increased pp, LAP did not change pp. No substantial increase inU _Na V was observed.The close correlation between ppU _Na V and pp LAP in HSI dogs supports the hypothesis that intrathoracic vascular receptors are involved in the mediation of volume regulation by stimulation of still unknown natriuretic mechanisms which operate on the tubular level in the presence of high mineralocorticoid activity.     

Urinary excretion of prostaglandin F2α and 6-keto-prostaglandin F1α during volume expansion in man

Renal function and the urinary excretion of immunoreactive prostaglandin F_2α (PGF_2α) and 6-keto-prostaglandin F_1α (6-keto-PGF_1α) were investigated during volume expansion (VE) in 9 healthy young adults. The studies were started after at least 17 h of food and fluid deprivation. Volume expansion (3% of body weight) was achieved by a continuous infusion of Ringer's solution (0.22 ml/kg/min). This increased the urinary excretion of sodium from 195±25 to 714±55 μmol/min/1.73 m²(mean ± S.E.) and decreased the excretion of potassium by 24% and plasma renin activity by 60% (P<0.01). The clearance of inulin increased slightly (from 102.4±3.7 to 114.5±6.2 ml/min/1.73 m², P<0.025), whüe clearance of PAH did not change. The excretion of immunoreactive PGF_2α decreased in 8 out of 9 individuals during VE, from 1.58±0.15 to 0.97±0.10 ng/min/1.73 m²(P<0.01). In contrast, excretion of immunoreactive 6-keto-PGF_1α increased in 8 out of 9 subjects, from 2.32±0.20 to 3.47±0.48 ng/min/1.73 m²(P<0.05). Urinary excretion of PGF_2α and 6-keto-PGF_1α may reflect renal synthesis of prostaglandins (PGs) and prostacyclin (PGI₂), respectively. The results indicate that synthesis of PGs is decreased and that of PGI₂ is increased during VE in man. However, no simple relationship could be found between the prostaglandins and the renal functional parameters.     

Renal potassium bicarbonate release in humans exposed to an acute volume load

Summary Cells of the renal medulla regulate their volume by transmembrane ion movements when exposed to large changes in osmolality. Since renal cells in culture release KHCO₃ in response to hypotonic stress [11], we investigated the effect of an acute water load on urinary KHCO₃ excretion in 5 healthy individuals. Water diuresis was induced by the ingestion of 1.51 hypoosmolal fluid (22 mosm/kg H₂O) over 15 min. The rate of urinary volume excretion increased from an initial value of 1.4 ml/min to 9.3 ml/min after 75 min. Urinary osmolality dropped from an initial value of 940±32 mosm/kg H₂O to 74±4 mosm/kg H₂O (n = 5). The decrease of osmolality was accompanied by the transient release of potassium and bicarbonate. Peak values of KHCO₃ excretion were observed between 30 and 45 min after the onset of the experiment corresponding to the drop of urinary osmolality. The magnitude of renal potassium release correlated significantly (r=0.93; P < 0.05) with endogenous plasma aldosterone concentrations measured prior to the experiment in the 5 volunteers. We conclude that medullary epithelial cells release KHCO₃ when exposed to hypotonic stress. The volume regulatory response is upregulated by aldosterone.Abbreviations ADH antidiuretic hormone - MDCK Madin-Darby canine kidney     

Percutaneous renal biopsy specimens in stone formers.

A series of renal biopsy specimens taken at the time of percutaneous nephrolithotomy were investigated for the presence and location of foci of microcalcification. Calcium was found in 18 of 25 (72%) of biopsy specimens from stone formers and in only seven of 30 (23%) of control biopsy specimens. This may indicate defective intrarenal handling of calcium as plasma calcium concentration was normal and 40% had a raised 24 hour urinary calcium excretion.     

Parathormone as a mediator of inorganic phosphate diuresis during saline infusion in the rat

Summary Normal rats were infused with isotonic saline at 0.50 ml/min for 2 hours in order to expand their extracellular fluid volume. Under these conditions fractional excretion of inorganic phosphate was found to be as high as 38.8±3.0% of filtered phosphate, while fractional sodium excretion was 12.9±0.7% of filtered sodium. The combined addition of calcium and magnesium to the infusion solution decreased inorganic phosphate excretion significantly (P<0.001) to 11.2±3.6% (presumably by inhibiting parathyroid gland activity), while sodium excretion was unchanged (13.5±1.1%). Parathyroidectomized rats were infused with isotonic saline at 0.50 ml/min to achieve a similar extent of extracellular fluid volume expansion as in the normal rats. In these animals inorganic phosphate excretion was as low as 0.9±0.9% of filtered phosphate, while sodium excretion was 11.8±2.2% of filtered sodium. Administration of parathormone to volume expanded parathyroidectomized rats resulted in marked increases or inorganic phosphate excretion to 41.5±3.1% of filtered phosphate (P<0.001), while sodium excretion remained unaltered (12.0±2.8% of filtered sodium), thus resembling very closely the results in normal volume expanded rats.From these results it is concluded, that saline induced phosphaturia in normal rats is mediated primarily by parathormone. Furthermore, sodium excretion during volume expansion of extracellular fluid appears to be independent of inorganic phosphate excretion and independent of changes in parathyroid activity.This work was supported in part by a grant from the Deutsche Forschungsgemeinschaft.