Lack of clinical evidence for a specific HIV-associated glomerulopathy in 203 patients with HIV infection.

Several authors described a high incidence of proteinuria with frequent progression to nephrotic syndrome and/or renal failure in patients with HIV infection. Though renal histological changes were rather non-specific, the existence of a specific, HIV-associated glomerulopathy was postulated. We repeatedly investigated proteinuria and serum creatinine in 203 HIV-infected patients. One hundred and twenty-two patients (group 1) had early stages of the disease without opportunistic infections, 81 suffered from acute opportunistic infections (group 2). In patients with a positive qualitative test (Combistix), quantitative measurement (Biuret) for proteinuria was carried out; when proteinuria was greater than 0.5 g/24 h, SDS gel electrophoresis was performed. None of the patients of group 1 had a proteinuria greater than 0.5 g/24 h or an elevated serum creatinine. Eleven of 81 patients from group 2 had a proteinuria between 0.5 and 3 g/24 h; one further patient of group 2 developed a transient proteinuria of 7.7 g/24 h. Only three of the proteinuric patients showed a glomerular pattern in SDS gel electrophoresis, all three during acute CMV or EBV infections. Fourteen of 81 group 2 patients showed a transient elevation of serum creatinine (x +/- SD of the maximum serum creatinines: 225.3 +/- 163 mumol/l), most during pentamidine therapy for Pneumocystis carinii infection; one patient treated with high-dose acyclovir had to be temporarily dialysed. In the investigated 203 HIV patients no nephrotic syndrome and no sustained elevation of serum creatinine greater than 200 mumol/l was observed. All cases of proteinuria and elevation of serum creatinine were associated with severe opportunistic infections and the administration of potentially nephrotoxic antibiotics.

High-flux synthetic versus cellulosic membranes for beta 2-microglobulin removal during hemodialysis, hemodiafiltration and hemofiltration.

Efficient removal of beta 2 microglobulin (beta 2-M) in end-stage renal failure patients is a continuing preoccupation, as the incidence and severity of dialysis-associated amyloidosis are increasing. To evaluate comparative beta 2-M removal we studied six stable end-stage renal failure patients during high-flux 3-h haemodialysis, haemodia-filtration, and haemofiltration, using acrylonitrile, cellulose triacetate, polyamide and polysulphone capillary devices. The reduction of plasma beta 2-M, total removal in ultrafiltrate/dialysate, and beta 2-M sieving coefficients were measured by RIA. The results suggest that convection plays the major role in beta 2-M removal when high-flux synthetic membranes are used in combination with high blood flow rates. In contrast, using the cellulose triacetate membrane under investigation, beta 2-M removal is diminished when ultrafiltration rates are increased. Accordingly, in any future prospective study on the role of beta 2-M retention in the amyloidogenesis, it is recommended that high-flux synthetic membranes be employed rather than the type of high-flux cellulosic membranes used in this study. The modality with which these synthetic membranes are used is probably less important, as long as maximum convective transport rates are obtained. Under present conditions, this will imply haemofiltration or haemodiafiltration rather than haemodialysis.

Is the rise in plasma beta-2-microglobulin seen during hemodialysis meaningful?

Beta 2-Microglobulin (beta 2M) plasma levels and levels of a second low-molecular-weight protein (myoglobin) were studied during a 2- to 4-hour sham dialysis period (no dialysate flow, no weight loss) and during a 4- to 5-hour hemodialysis (HD) with a Cuprophan capillary dialyzer. While no rise of the beta 2M or myoglobin levels occurred during sham dialysis, a rise of 22.1 +/- (SD) 8.5% (beta 2M) or 19.9 +/- 12.1% (myoglobin) was seen during regular HD. The increases of both molecules showed a significant correlation (r = 0.44; p less than 0.03). Both rises could not be completely abolished using correction factors for hemoconcentration. The rises occurred irrespectively of the dialysate buffer. The results suggest that neither the Cuprophan membrane nor the extracorporeal circuit were responsible for the rise of both molecules during HD. It seems more likely that changes of the extracellular volume and extra- to intracellular water shifts are involved and account for the majority of the rise. However, the possibility of minor increase in the extracellular mass of beta 2M or myoglobin cannot be excluded completely.

Is renal involvement a prognostic parameter in patients with infective endocarditis?

Renal involvement (RI)--defined as proteinuria greater than 150 mg per 24 h with haematuria or impaired glomerular filtration rate--was studied in 80 patients with infective endocarditis (IE). Proteinuria was measured quantitatively and further differentiated by the SDS-polyacrylamide-gel electrophoresis. RI was found in 40 patients (50%) with proteinuria from 150 to 8000 mg per 24 h. SDS-PAGE revealed a tubular protein pattern in 17 patients, a glomerular pattern in 6 and a glomerulo-tubular pattern in 17. Mortality rate was significantly higher in patients with RI (40%) than in those without (7.5%), and was not related to the type of infected valve, infective organisms, method of treatment (surgical or medical) or embolic events. Following successful treatment of IE, 18 out of 23 patients showed complete normalization of renal function. Renal involvement in patients with IE may be of prognostic significance--indicating an impaired prognosis.

Uptake of polyvinyl alcohol by macrophages in the glomerular mesangium of rats. Histologic and functional studies.

Rats received daily subcutaneous injections of the synthetic polysaccharide polyvinyl alcohol (PVA) for 1-28 days. The amount of PVA localized in the glomerular mesangium increased progressively during this time. By 28 days, all glomeruli showed extensive intracellular mesangial sequestrations of PVA, causing marked widening of mesangial areas, while the peripheral capillary loops were unaltered. Overall glomerular hypercellularity was mild to moderate, occurring mainly in areas of PVA deposition. Follow-up studies after 6, 12, 26, and 40 weeks revealed partial reduction of glomerular PVA masses. The PVA deposits were frequently associated with nonspecific esterase (NSE)-positive cells. The number of NSE-positive cells per glomerular tuft section increased from 0.1 in controls, to 2.1, 4.0, and 4.5 after 3, 14, and 28 days of PVA treatment, respectively. Similarly, glomerular counts for Ia-antigen-bearing cells rose from 2.1 in controls to 4.8 on Day 3 and showed further increases at later time periods with confluent staining of clusters of Ia-positive cells. In glomeruli, Ia-bearing cells were mainly noted in PVA-positive mesangial areas. These results indicate that PVA is taken up in the glomerulus primarily by cells that are NSE- and Ia-antigen-positive, suggesting that these cells are activated blood-borne monocyte-macrophages that sequester this polysaccharide. Clearance studies revealed that the glomerular filtration rate and effective renal plasma flow remained normal after 4 weeks of PVA injections. PVA-treated rats showed only mild elevations of urinary protein excretion. These findings indicate that confinement of marked structural and cellular alterations to the mesangium, even including the presence of infiltrating monocyte-macrophages, is compatible with absent or minimal dysfunction of the glomerular ultrafilter.

[Pheochromocytoma in pregnancy--pathophysiology and therapy (author's transl)]. / Das Phäochromozytom in der Schwangerschaft--Pathophysiologie und Behandlungsmöglichkeiten.

In this paper pathophysiology of pheochromocytoma and its modern diagnostic and therapeutic management are discussed with special regard to the combination of pheochromocytoma and pregnancy. The preoperative treatment with phenoxybenzamine is evaluated. As for the anesthetic management barbiturates and neurolept anesthesia are recommended. In the acute treatment of extreme blood pressure values sodium nitroprusside is preferred to phentolamine. Whereas vaginal delivery is contraindicated in a patient with pheochromocytoma there is no definite superiority of tumorresection along with caesarean section against a separate abdominal procedure.

Renal sodium conservation during starvation in the rat.

The phenomenon of natriuresis during the early phase of total starvation has been described in man and rabbit. We have examined the pattern of electrolyte excretion initiated by starvation for 4 days in the male Wistar rat. Within 24 hr sodium excretion is significantly diminished when compared to prestarvation values (control 2.55 +/- 0.76 [S.D.] mEq/day; 1-day fast 0.42 +/- 0.27) and by day 2 is less than one tenth of the control value. Chloride retention parallels this sodium conservation. Concomitant changes in urinary pH and ammonia excretion (UNH4V) reflect the mild acidosis of starvation (control pH 7.46 +/- 0.18 [S.D.], UNH4V 0.21 +/- 0.08 [S.D.] mEq/day; day 2 pH 6.10 +/- 0.31, UNH4V 0.71 +/- 0.21). However, the excretion of organic acids is not elevated but is actually decreased by day 2 (control 1.02 +/- 0.21 [S.D.] mEq/day; day 2 0.66 +/- 0.26). The majority of the organic acids are excreted as salts (day-2 0.51 +/- 0.21). This level of excretion does not obligate excessive sodium loss and can be adequately matched by renal ammonia production. Normal plasma glucose levels are maintained, consistent with the well-documented increase in renal gluconeogenesis in the starved rat. Plasma levels of glucagon, a known natriuretic and ketogenic agent, do not rise, and this together with a normal plasma glucose concentration may account for the failure of the rat to exhibit the natriuresis of starvation that is observed in man and rabbit.

[The clinical significance of hyperuricemia for the prognosis of pregnancy toxemia]. / Klinische Bedeutung der Hyperurikämie zur Prognose bei EPH-Gestose.

This study demonstrates that uric acid serum levels are of importance in the prognosis of pregnancy complicated by hypertension. In early pregnancy the uric acid level probably is the most sensitive parameter to select the risk-prone pregnancies with EPH-gestosis to conduct the further course of pregnancy under medical care. Pregnant hypertensives with high uric acid levels develop more often retardation of the fetus, the incidence of eclampsia increases. In case of hypertension in pregnancy complicated by high uric acid levels careful monitoring and normalizing high blood pressure under medical observation improves the prognosis for fetus and mother.

Renal tubule ion transport and collecting duct function in the elasmobranch little skate, Raja erinacea.

Renal micropuncture and microdissection techniques with ultramicro fluid analysis have been applied to evaluate single nephron function in the skate, Raja erinacea. We have divided the skate nephron into three proximal tubular segments (PTS I-III), three distal coilings (DC I-III), and a countercurrent loop system located between the proximal segments and the distal coilings. The collecting duct is the principal site of urinary dilution. Following exposure of the fish to 75% seawater for about 24 hours, the sodium concentration difference between the end collecting duct lumen and plasma is decreased sufficiently to account for the urinary dilution. The principal site for magnesium, phosphate and sulphate secretion appears to be PTS II. This segment is located on the ventral surface of the kidney. PTS II is also the main nephron site for reabsorption of sodium and chloride in excess of water.

Role of sodium and water in hypertensive patients on maintenance hemodialysis.

In 46 patients of the chronic hemodialysis program blood pressure regulation was studied according to variations of sodium and fluid balance. A strong relationship was observed between blood pressure and the amount of exchangeable sodium. In the hypertensive patients exchangeable sodium was increased depite fulfilled clinical signs of sufficient dehydration. The blood volume was found to be small and the plasma renin activity increased in those hypertensive patients, in which sufficient fluid depletion was inhibited by extreme fluctuations of the blood pressure during dialysis. A diminution of the sodium concentration keeping the fluid balance constant induced an increase of blood pressure and deteriorated the subjective feeling of the patients. By an increase of the sodium concentration up to 155 mEq/l severe blood pressure fluctuations during during dialysis could be prevented, although further fluid was taken off by ultrafiltration. This effect seemed to be mediated--at least partly--by an increase of the low blood volume and a suppression of plasma renin activity. After the patients became normotensive, dialysis procedure could be continued with normal sodium concentration. By a temporary high sodium regimen of the dialysis procedure some patients with renal failure and 'uncontrollable hypertension' can be preserved from bilateral nephrectomy.

Effect of angiotensin on the filtration of protein in the rat kidney: a micropuncture study.

We have analyzed the protein content of proximal tubular fluid (PTF) by ultramicro disc electrophoresis and measured total protein excretion rates both in control conditions and during angiotensin infusion to the rat. Under control conditions PTF albumin concentration was 1.49 +/- 1.12 (SD) mg/100 ml and did not increase with distance from the glomerulus. Immediate postcapsular samples (Munich-Wistar strain) yielded nearly identical values so that both probably represent filtered albumin concentration. During infusion of angiotensin (0.15 mug/mix x 100 g of body wt), PTF albumin concentration increased on the average 26-fold in re-collections from control tubules. Total protein excretion increased from a control of 7.91 to 24.37 mg/24 hr x 100 g of body wt. Glomerular filtration rate (FGR), single nephron GFR (SNGFR), proximal transit time and tubular fluid to plasma (tf/p) inulin values did not change significantly. Net afferent filtration pressure decreased from 24.7 to 15.6 mm Hg and renal plasma flow fell from 2.16 to 1.31 mo/min x g of kidney wt. Data describe a protein reabsorptive system normally operating near capacity. Angiotensin-induced proteinuria derives from an increase in filtered protein (mostly albumin) resulting from permeability changes in the glomerular membrane.

Effect of angiotensin on glomerular filtration of albumin.

Angiotensin-induced proteinuria was examined at the glomerular-tubular level in rats. Ultra-micro-disc electrophoresis was employed to determine albumin concentration of rat proximal tubular fluid samples under control conditions and during the infusion of 0.15 mug/min X 100 g body weight angiotensin II using micropuncture techniques. Under control conditions proximal tubular albumin concentration was 1.32 +/- 0.79 (SD) mg/100 ml (n = 71). There was no correlation between albumin concentration and (TF/P)-inulin ratio indicating an albumin reabsorption in the proximal tubule parallel to fluid reabsorption under control conditions. During angiotensin infusion using re-collection techniques, there is an average increase of 26 times in tubular albumin concentration, indicating an increase in albumin filtered. There was no change in GFR, SNGFR, transit time, (TF/P)-inulin ratio, an increase in urine flow rate, sodium excretion, protein excretion, mean arterial blood pressure during angiotensin infusion. Since effective glomerular filtration pressure was not increased during angiotensin it is concluded that angiotensin-induced proteinuria is due to an increase in filtered protien mediated by a change in glomerular permeability to proteins.

Amino acid reabsorption in the rat nephron. Free flow micropuncture study.

The concentration of nine endogenous free L-alpha-amino acids (ALA, LEU, ILE, PHE, TYR, LYS, GLU, PRO, GLY) and of taurine were determined simultaneously along the nephron of the rat kidney using free-flow micropuncture techniques without altering plasma amino acid concentration or kidney function. The amount of each amino acid was determined after dansylation (14C-labelled dansyl-chloride) in the micropuncture sample followed by thinlayer chromatography. The main site of reabsorption is the proximal tubule. After 15-20% of the proximal tubule length the bulk of reabsorption has taken place (18.9 plus or minus 3.4% S.E. of the filtered load remaining). Net reabsorption continues to a small but significant extent along the distal nephron (disal tubule and collecting duct). Reabsorption of taurine is less rapid (% remaining of filtered load at the early proximal tubule 37.0 plus or minus 4.6%). The transtubular concentration ratio of all amino acids except taurine follows a homogeneous course. Under the experimental conditions of this study no distction with respect to different systems of reabsorption "neutral", "basic", "acidic", "imino-glycine") could be made.

Glomerular protein filtration in normal and nephritic rats. A micropuncture study.

The acute heterologous phase of anti-basement membrane glomerulonephritis in rats was studied morphologically and functionally at the single nephron level. In samples drawn from Bowman's space or from the very early segment of the proximal tubule the protein content was measured by ultra micro-disc-electrophoresis. Morphologically, in rats which were treated with anti-glomerular basement-membrane serum (AGBM) no significant changes could be seen in light microscopy whereas in immunohistology the typical, linear, subendothelial fluorescent staining for IgG could be seen. In controls, small amounts of albumin were filtered (7.57 +/- 0.66 mug/min X 100 g body weight, n = 14) but in nephritic animals the filtered load of albumin increased significantly to 58.33 +/- 4.10 mug/min X 100 g body weight, (n = 8). Besides this increased albumin filtration also several serum globulins could be detected, whereas in controls they were missing. Total GFR and proximal passage time did not change significantly. It is concluded that the glomerulus is an effective barrier for protein under control conditions and that it becomes permeable for albumin and higher molecular weight serum proteins following the antigen antibody reaction at the glomerular basement membrane in the AGBM-treated animals.