A. Z. Gyory

Arginine vasopressin and osmolality in the elderly

Objectives: To evaluate the influence of age on plasma arginine vasopressin (AVP) concentrations and the relationship between plasma AVP and serum osmolality in younger and older subjects, and in the elderly, to assess the effect of gender on plasma AVP concentration and to determine the impact of prostaglandin blockade on renal responsiveness to AVP.

Transport characteristics of human proximal tubule cells in primary culture

Summary: In order to establish an in vitro model for studying human proximal tubule transport, primary culture of human proximal tubule cells (PTC) was carried out using an improved technique and the properties of these cells were characterised in detail. Using a combination of collagenase treatment, mechanical sieving and isopycnic ultracentrifugation, large numbers of highly purified populations of PTC were isolated and propagated from histologically normal regions of human nephrectomy specimens. Cultured human PTC demonstrated typical histologic and ultrastructural morphologies, well‐preserved brush border enzyme activities, and cyclic adenosine monophosphate (cAMP) production which was stimulated by parathyroid hormone (PTH) but not by vasopressin. Tight confluence, as evidenced by relative impermeability to the paracellular diffusion of inulin, was achieved on porous membrane inserts within 6–8 days. Confluent monolayers generated Na+, K+, Cl−, HCO3− and PO43‐ concentration gradients between apical and basolateral medium compartments, which correlated well with the reabsorption processes known to occur in human PTC in vivo. A number of polarised transport systems were demonstrated, including phlorizin‐inhibitable apical Na+‐glucose transport, PTH‐inhibitable apical Na+‐phosphate transport, probenecid‐inhibitable organic anion transport and quinine‐inhibitable organic cation transport. Using microspectrofluorimetric and 22Na+ uptake measurements, pharmacologically distinct apical and basolateral sodium‐hydrogen exchangers (NHE) were identified. Apical NHE was significantly inhibited by micromolar concentrations of phorbol esters, ethylisopropylamiloride (EIPA) and 3‐methylsulphonyl‐4‐piperidino‐benzoylguanidine methanesulphonate (HOE694). the mean resting intracellular pH of human PTC was 7.23 ± 0.04 and the mean intrinsic buffering capacity following a 20 mmol/L NH4Cl prepulse was 28.45 ± 0.96 mmol/L/unit pH. the results suggest that human PTC, prepared for culture as described herein, maintain morphological and physiological properties characteristic of the segment in vivo. the method therefore provides a useful model for the study of highly polarised transport processes in the human proximal tubule.

Tubular sodium handling and tubuloglomerular feedback in compensatory renal hypertrophy

Tubular sodium handling and tubuloglomerular feedback (TGF) activity were assessed in established compensatory renal hypertophy in Sprague Dawleys rats. Hyperfiltration at the level of the single nephron was confirmed 4–6 weeks following a reduction in renal mass. TGF activity, determined as the difference between late proximal and early distal measurements of single-nephron glomerular filtration rate (SNGFR), was significantly increased in compensatory renal hypertrophy, being 7.8±1.0 vs 23.3±1.9 vs 25.5±2.6 nl/min (P for analysis of variance <0.05) following sham operation, unilateral nephrectomy, and 1 1/3 nephrectomy, respectively. Enhanced net tubular Na transport was also observed, with total Na reabsorption up to the late proximal site being 1.8±0.2 vs 2.7±0.1 vs 3.1±0.3 nmol/min (P<0.05), and to the early distal site being 3.4±0.5 vs 5.8±0.6 vs 7.9±0.8 nmol/min (P<0.05) in the three animal groups respectively. Comparison of proximal tubular length demonstrated a 71.9±8.1% increase in uninephrectomised vs sham-operated animals. This increase was proportionately greater than the increase in proximal Na reabsorption (50.0±4.0%) observed in the corresponding animal groups. Concurrent electron microprobe experiments in uninephrectomised and sham-operated animals demonstrated that the proximal tubular intracellular Na concentration was significantly lower following uninephrectomy (16.8±0.6 vs 18.9±0.5 mmol/kg wet weight, P<0.01), in association with evidence of reduced basolateral Na/K-ATPase activity. In summary, these data indicate that total Na transport in individual nephrons is increased in the proximal tubule and in the loop of Henle in compensatory renal hypertrophy, although the net amount of Na reabsorbed per unit proximal tubular length is actually reduced. The cell composition data suggest that the site of inhibition of transcellular transport is at the apical cell membrane. The elevated SNGFR is under the regulatory influence of an appropriately activated TGF system, which serves to limit the hyperfiltration.

Renal Function in Unilateral Nephrectomy Subjects

Renal function in 32 subjects who had undergone unilateral nephrectomy (17 transplant donors and 15 subjects with unilateral renal disease) was compared with that of 22 normal subjects. The age-adjusted glomerular filtration rate was lower in transplant donors (79 +/- 15% of normal) than in those whose nephrectomy was performed for unilateral renal disease (90 +/- 12% of normal). The donors were also significantly older at nephrectomy (48 +/- 10 years versus 24 +/- 13 years, p less than 0.001). This finding may represent less capacity for compensatory hypertrophy. Proximal tubular and medullary function as assessed by 15-minute phenolsulfonphthalein excretion, maximum urinary concentration in response to water deprivation plus exogenous vasopressin, and urinary acidification in response to an oral acid load were all within normal limits for glomerular filtration rate. Overall renal function was well preserved after nephrectomy. A small number of patients did have increased cast excretion, which may signify the presence of mild renal disease in these subjects.

Plasma Volume Contraction: A Significant Factor in Both Pregnancy-Associated Hypertension (Preeclampsia) and Chronic Hypertension in Pregnancy

The role of plasma volume in hypertension in pregnancy (pre-eclampsia) was investigated. Significant volume expansion from non-pregnant levels (16.5 +/- 1.60 ml/cm height) was present throughout pregnancy in 189 normal women, reaching 23.1 +/- 1.21 ml/cm at 33-36 weeks amenorrhoea. In another 40 initially normotensive pregnant women who developed hypertension, similar early volume expansion was followed by significant volume contraction in the third trimester, before evaluation of blood pressure in 29 (20.6 +/- 1.26 ml/cm), after it in 11 (18.6 +/- 1.27 ml/cm). Equivalent volume contraction was present in another 44 women studied only after hypertension developed in the third trimester. Oedema had no value as a clinical sign. In another 30 women with chronic hypertension, blood pressure was inversely related to plasma volume (r = 0.822) and to fetal growth (r = -0.710), which was directly related to plasma volume (r = 0.701). Plasma volume depletion plays a significant role in hypertension in pregnancy.

Low-Dose Aspirin in High-Risk Pregnancy?

Objectives: To determine the value of low-dose aspirin (100 mg/day) therapy in high-risk pregnancies, and to assess improvement in maternal abnormalities in response to this therapy, we conducted a prospective, randomized, double-blind, placebo-controlled therapeutic study.Methods: One hundred and eight pregnant women with preexisting hypertension (n = 60) or renal disease (n = 28), or a history of early severe preeclampsia (n = 20) in a previous pregnancy, took either aspirin (n = 58) or placebo (n = 50) from 17 to 19 weeks amenorrhea till approximately 37 weeks amenorrhea. The main outcome measures were duration of pregnancy, birth weight, maximum antenatal blood pressure, and maximum antenatal serum uric acid level.Outcome: Median values for the maximum antenatal blood pressure were higher and for birth weight lower in placebo-treated than in aspirin-treated women. Noncompliance with treatment, as assessed by platelet aggregation studies, was high in both groups.Conclusion: There was a small but potent...

HAEMODYNAMICS OF HYPERTENSION IN PREGNANCY ASSESSED BY M-MODE ECHOCARDIOGRAPHY

1. Echocardiographic haemodynamic and left ventricular parameters were determined in twenty‐one normotensives and thirty‐six hypertensives during the last trimester of pregnancy.

Recognition and Management of IgA Nephropathy

SummaryIgA (immunoglobulin A) nephropathy is the most common form of primary glomerulonephritis worldwide. It generally has a good prognosis, with 15-year rates of kidney survival from the apparent onset of disease usually well in excess of 70%. Progression, when it occurs, is usually a slow, indolent process, and spontaneous remission of disease activity occurs in 7% of patients.It is possible to predict, from the initial presenting features and laboratory findings, renal biopsy and clinical course during follow-up, which patients are likely to have progressive renal disease. Identification of the factors likely to be associated with progression is of importance in helping to establish which patients will benefit from specific therapeutic intervention.For all patients, attention should be directed toward general health issues in an endeavour to reverse factors that are likely to have an adverse impact on renal function. This should include early detection and tight control of hypertension (present in 50% of all patients with IgA nephropathy during the course of their disease), along with utilisation of antihypertensive agents that have specific renoprotective effects, namely ACE inhibitors or calcium antagonists. Such therapy should also be considered in normotensive patients with heavy proteinuria, as a reduction of proteinuria is often achieved by this means.Other aims should include maintenance of desirable bodyweight, correction of hyperlipidaemia, cessation of smoking, participation in an active exercise programme, avoidance of exposure to nephrotoxins and maintenance of a high fluid intake. A low protein/low phosphate diet together with phosphate binder therapy should be commenced early in the course of renal impairment. Corticosteroid and/or cytotoxic drug therapy should be considered in the small percentage of patients with heavy proteinuria or a rapid decline in renal function. Such therapeutic endeavours are likely to delay the onset of renal failure in patients with progressive IgA nephropathy.

Relation between active sodium transport and distance along the proximal convolutions of rat nephrons: Evidence for homogeneity of sodium transport

SummaryThe transepithelial sodium (Na) concentration difference at steadystate (Δceq) was measured in the proximal convolutions of surface nephrons of the rat kidney using peritubular and stopped-flow microperfusion techniques. The measurements were made at various sites along the convolution over a wide range of intraluminal Na concentrations. Over a concentration range from 35 to 400 mmol/kg H2O no correlation was found between the size of Δceq and the location of the perfusion site within the convolution. It was concluded that the proximal convolution was homogeneous with respect both to theKm and theVmax of the Na transport system.

Proximal tubular cell sodium concentration in early diabetic nephropathy assessed by electron microprobe analysis

Electron microprobe X-ray analysis techniques were employed in order to assess the changes that occur in proximal tubular cell sodium concentration during the hyperfiltration phase of early diabetes mellitus induced by streptozotocin in Sprague Dawley rats. Intracellular rubidium accumulation following intravenous infusion of rubidium chloride was used as a marker of basolateral Na/K-ATPase activity. The diabetic animals studied had a significantly higher glomerular filtration rate compared with controls [1.44±0.07 vs. 1.00±0.07 ml min−1 (100 g body weight)−1; mean±SEM, P<0.001]. Intracellular Na concentration was significantly higher in diabetic animals (19.5±0.6 vs. 17.8±0.4 mmol/kg wet weight; P<0.01). Concurrent measurement of Rb demonstrated significantly higher intracellular accumulation in the proximal tubules of diabetic animals compared with control (7.9±0.5 vs. 5.5±0.5 mmol/kg wet weight; P<0.001). These results indicate that proximal tubular Na/K-ATPase activity is enhanced in the hyperfiltration phase of diabetes mellitus. Since, however, intracellular Na concentration is increased under these conditions, it may be inferred that apical Na entry into proximal tubular cells is stimulated beyond the rate of basal exit during the initial development of hyperfiltration. The reasons for these alterations in cellular Na transport are unclear but similar changes have been implicated in the pathogenesis of cell growth.