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We report the case of a 63-year-old man who presented with acute kidney injury, active urine sediment, nephrotic syndrome, and hypocomplementemia after a recent report of a sore throat. Kidney biopsy showed diffuse proliferative and exudative glomerulonephritis with C3-dominant staining by immunofluorescence. Taken together, clinical and pathologic findings were most suggestive of acute postinfectious glomerulonephritis, although the history of full nephrotic syndrome, presence of segmental membranoproliferative features, and absence of classic subepithelial hump-shaped deposits were unusual for this condition. Three months after the initial biopsy, the patient continued to have hypocomplementemia and nephrotic syndrome, prompting a repeated kidney biopsy that showed findings most consistent with C3 glomerulopathy. C3 glomerulopathy is a proliferative pattern of glomerulonephritis characterized by complement deposits that stain solely or dominantly for C3. A subset of cases of C3 glomerulopathy have features that overlap extensively with acute postinfectious glomerulonephritis. Clinicians and pathologists should be aware of the similar findings seen in these 2 conditions.

Wearable blood processing devices offer an attractive solution to problems inherent in clinic-based, intermittent end-stage renal disease therapies. What is involved in transitioning even a part of the current clinic-based population to ambulatory therapy has not been clearly enumerated. This paper addresses what a first-generation wearable device might accomplish, how issues of safety will need to be addressed, and what will make the device attractive to, and manageable by, the patient. Medical, technological, and economic issues are identified.

About 65 million Americans, one fourth of the adult population in the United States, and over 1 billion people worldwide have hypertension (HTN). HTN therefore is present in 1 of every 4 patients admitted to any US hospital. Surprisingly, no guidelines are available for the management of inpatient HTN. Based on a comprehensive search of the literature we are proposing a pathway for the management of HTN in nonpregnant hospitalized patients. The pathway provides a definition and clinical assessment of HTN for patients admitted to the hospital. The assessment is followed by an organ/system based therapeutic approach specifying timing, blood pressure goals, recommended antihypertensive drug therapy and the sequence of add-on drugs. The pathway specifically discusses assessment and management of HTN in patients with (1) acute aortic syndrome, (2) acute neurologic syndrome, (3) acute coronary syndrome, (4) congestive heart failure, (5) renal failure, and (6) secondary forms. Finally, the pathway provides a step by step recommendation for the management of in hospital HTN and of hypertensive emergencies.

Although the treatment of atherosclerotic renal artery stenosis with percutaneous angioplasty, stenting, and surgical revascularization has gained widespread use, few prospective randomized controlled trials (RCTs) exist that compare these techniques with each other or against the standard of medical management alone. To facilitate this process and help answer many important questions about the appropriate application of renal revascularization, well-designed and rigorously conducted trials are needed. These trials must have clearly defined goals and must be sufficiently sized and performed so as to withstand intensive outcomes assessment. Toward this end, the present statement provides guidelines and definitions for the design, conduct, evaluation, and reporting of renal artery revascularization RCTs. In addition, areas of critically needed renal artery revascularization investigation are identified. It is hoped that this information will be valuable to the investigator who wishes to conduct research in this important area. The use of revascularization techniques for the management of renal artery stenosis in patients with hypertension, renal insufficiency, pulmonary edema, and unstable angina has become increasingly prevalent. Renal artery stent placement, in particular, has gained increasing acceptance on the basis of historical results of renal angioplasty1–3⇓⇓ and the attractiveness of percutaneous compared with surgical revascularization.4 Despite extensive clinical experience over the past 10 years and the publication of multiple articles describing renal revascularization with renal artery stents,5–23⇓⇓⇓⇓⇓⇓⇓⇓⇓⇓⇓⇓⇓⇓⇓⇓⇓⇓ renal angioplasty,24–47⇓⇓⇓⇓⇓⇓⇓⇓⇓⇓⇓⇓⇓⇓⇓⇓⇓⇓⇓⇓⇓⇓⇓ and surgical renal revascularization,48–66⇓⇓⇓⇓⇓⇓⇓⇓⇓⇓⇓⇓⇓⇓⇓⇓⇓⇓ few prospective RCTs have been reported.4,67–71⇓⇓⇓ …

Abstract We previously have shown that Dahl salt-sensitive rats increase renal vascular resistance in response to excessive salt feeding before total peripheral resistance increases and hypertension occurs. Failure of renal vasculature to dilate, as normally occurs in Dahl salt-resistant rats fed a high salt diet, may play a role in the development of hypertension in Dahl salt-sensitive rats. We also showed that renal vasculature in salt-sensitive rats is hyperreactive to vasoconstrictors and hyporeactive to vasodilators. Atrial natriuretic peptide, by stimulating cell-bound receptors, and nitroprusside, by generating nitric oxide, cause renal vasodilation by generating cGMP. Studies were undertaken to determine whether defective renal vasodilation in Dahl salt-sensitive rats is due to impaired production of cGMP. We examined the influence of nitroprusside infusion and salt intake on renal vascular resistance and cGMP excretion in salt-sensitive and salt-resistant rats. Results demonstrate that salt feeding and nitroprusside infusion increase cGMP excretion and decrease renal vascular resistance in salt-resistant rats ( P P

Background: Although prior studies have shown that frequent hemodialysis (HD) can lead to improved control of dry weight in end-stage renal disease patients, there are no clinical studies examining whether this can improve blood pressure (BP) control and can also shorten the dialysis time needed to achieve satisfactory removal of small molecules. Several models of wearable dialysis systems are now under various stages of development. These devices present the possibility of hemodialyzing patients to their dry weights. We have built a prototype of a wearable ultrafiltration (UF) device that can provide daily UF. Apart from better fluid control, we hypothesize that separating HD from UF will result in better BP control, and adequate weekly small molecule removal could be achieved with a decreased duration of dialysis. We tested the hypothesis in current HD patients using conventional dialysis equipment. Methods: Thirteen patients were selected from a large urban HD center. The experimental period consisted of 4 weeks of daily UF (4 days/week of UF alone and 2 days/week of HD with UF). The duration of the HD sessions was increased by 15–30 min to maintain weekly standard Kt/V >2.0. The patients were then returned to their conventional 3 days/week of HD with UF and studied for 4 weeks. Predialysis BPs, interdialytic weight gains, and Kt/V results of the experimental and return periods were compared with those of the 3-month control period. No changes were made in antihypertensive or other medication during the study. Results: During the experimental period, mean arterial pressure decreased from 110 to 95 mm Hg (p < 0.001), systolic BP from 158 to 136 mm Hg (p < 0.001), while interdialytic weight gains were reduced from 3.25 to 1.21 liters (p < 0.0001). During the experimental period, weekly standard Kt/V of 2.16 was achieved in 8.24 h/week of HD, as compared to 11.14 h/week. Conclusions: Volume control with daily UF results in improved BP control and, by separating the UF function from HD, adequate weekly standard Kt/V >2 can be achieved with twice weekly HD.

That patients with nephrotic syndrome are at an increased risk of developing renal vein thrombosis (RVT) is well established.1,2 However, whether RVT as an isolated event can cause nephrotic range proteinuria is not well documented. A 61-year-old Caucasian male, with history of hypertension, diabetes, obesity, deep venous thrombosis with placement of an inferior vena cava (IVC) filter (5 years ago), presented with an abrupt onset of gross hematuria and severe back pain. Pertinent laboratory results included an increased serum creatinine of 2.3 mg/dl (baseline 1.3 mg/dl). Computed tomography (CT) scan of the abdomen revealed bilateral renal vein thrombosis. The right renal vein was fully and the left partially occluded. The IVC filter was displaced and adjacent to the renal veins. …

Acute kidney injury in HIV patients is primarily related to HIV-mediated viral or immunological disease or to treatment-related toxicity (tenofovir). Neoplasms are a rare cause of non-obstructive acute kidney injury, primarily because when they occur, they manifest as discrete masses and not as diffuse infiltration of the renal parenchyma. Diffusely infiltrating tumors include carcinoma of the renal pelvis invading the renal parenchyma, renal lymphoma, squamous cell carcinoma (from lung) metastasizing to the kidney and infiltrating sarcomatous type of renal cell carcinoma. To be classified as a true case of renal lymphoma, the tumor should have escaped detection on routine imaging preceding biopsy, and lymphoma-associated renal failure/nephrotic proteinuria should have given rise to the indication for kidney biopsy. We present here a case of an acute kidney injury due to renal lymphoma in a patient with acquired immune deficiency syndrome that manifested clinically as bland urine sediment, minimal proteinuria and normal-sized kidneys. Chemotherapy resulted in complete reversal of acute kidney injury.

Inherent limitations in the suitability of drainage volumes for monitoring intraperitoneal fluid volume have resulted in the frequent use of indicator dilution techniques, but little attention has been given to confirming the adequacy of the estimates that volume markers provide. In a series of experimental exchanges in rats, volume estimates were compared based on the dilution of blue dextran and hemoglobin with direct collections of surgically exposed intraperitoneal fluid. Significant systematic and random errors in the indicator dilution volume estimates were observed. The systematic errors appeared to be due to the rapid removal of a fixed amount of marker from peritoneal fluid, while the random errors were caused by the rapid appearance of a variable amount of endogenous chromogen. The behavior of the markers observed in this study was not consistent with the assumptions commonly used to analyze volume transport inperitoneal dialysis.

Direct contact between uremic blood and a fluid capable of receiving uremic toxins is possible. Such contact by itself is, however, not beneficial because the selection of molecules that are removed is dependent on diffusion coefficients in blood. This selection is inadequate and would result in the exhaustion of a patient's albumin pool before useful reduction in the urea pool was achieved. Direct contact that is accomplished by sandwiching blood between two layers of a sheathing fluid, followed by diafiltration of the sheathing fluid through conventional membranes and recirculation of the sheathing fluid, is possible. This adaptation of membraneless transport of molecules from blood eliminates almost all contact of blood with solid artificial surfaces and the subsequent diafiltration and recirculation of the sheathing fluid allows precise control of what is removed from the system. Slightly hyperosmotic protein is carried back by the recirculating sheathing fluid. Only solutes and water that pass the diafilter, which operates on a cell-free fluid, are able to leave the system. The system depends strongly on the ability to keep cells out of the sheathing fluid. Preliminary results and earlier reports indicate that this separation is possible and more precise measurements are underway. A quantitative design of a wearable dialyzer based on a circulating sheathing fluid is presented.

Direct contact between uremic blood and a fluid capable of receiving uremic toxins is possible. Such contact by itself is, however, not beneficial because the selection of molecules that are removed

To the Editor, We present here a scenario of acute renal failure in the setting of blue toe syndrome. A 62-year-old male with a past medical history of hyperlipidaemia, hypertension and stroke presented with a 2-week history of severe diarrhoea, generalized weakness and myalgias. His home medications included Lipitor, Coumadin, Lopressor, Aspirin and lisinopril. During his prior hospitalization, one and a half months ago, he had undergone coronary artery bypass graft which was complicated by an ascending and descending aortic dissection post-operatively. The ascending dissection was surgically repaired. The origin of the celiac axis, superior mesenteric artery and renal arteries was from the true lumen, and thus, the blood flow was not compromised from the descending aortic dissection (Figure 1a). On examination, the patient’s blood pressure was 157/91 mmHg and pulse 85 beats/minute of equal strength in both upper and lower extremities. His systemic examination was significant for painful bluish discoloration of the toes bilaterally (Figure 1b). Initial laboratory results revealed blood urea nitrogen 111 mg/dL, serum creatinine 10.8 mg/dL, potassium 5.8 mEq/L, bicarbonate 15 mEq/L and creatinine phosphokinase 12 893 IU/L. Complement C3 level was decreased. Urine analysis did not reveal muddy brown casts. The remainder of the laboratory panel was also unremarkable. Lipitor was discontinued. Despite adequate hydration, the patient remained oliguric with no improvement in his renal function (Figure 1c). In the setting of surgical history and blue toe syndrome, an atheroembolic phenomenon as the cause of renal failure was considered. Direct ophthalmoscopy and slit lamp examination of the eye revealed cholesterol crystal emboli in the retinal arterioles (Hollenhorst plaques, Figure 1) and thus confirmed the diagnosis of atheroembolic disease. The patient was started on haemodialysis. Fig. 1 (a)The aortic dissection/aneurysm at the level of the left renal artery measured 3.5 cm, and the renal arteries originated from the true lumen. In addition, there was no evidence of aortic leak, and at the level of the origin of the celiac artery and ... Atheroembolic disease may present with general symptoms of fever, myalgias, headache, weight loss and diarrhea [1]. Though sometimes subtle, the pathological process of dislodging multitude of cholesterol crystals from atherosclerotic plaques in the arteries (often post-operatively) can manifest symptomatically diversely. The emboli may travel to the capillary beds of the renal, mesenteric, retinal, tibial and peroneal arteries capable of producing digital or skin ischaemia, and even overt organ failure. Therefore, a high degree of clinical suspicion is warranted since, in the setting of gastrointestinal symptoms, abnormal renal parameters may be confused for acute renal failure secondary to severe dehydration. While the cholesterol showers to the lower extremities are often labeled as ‘blue toe syndrome’, the actual cutaneous manifestations of the bluish discoloration are uncommonly seen in only 5% of patients with atheroembolic disease [1]. In our patient, the blue toes were the sole dermatological manifestation. Other more classical manifestations include cord-like purplish cutaneous discoloration in the lower extremities (livedo reticularis). Acute renal failure is present in 25–50% of atheroembolic cases [2]. Although the disease commonly occurs after invasive vascular procedures (i.e. coronary angiography via femoral artery), instances of spontaneous embolization have also been reported. In the latter cases, the diagnosis may be difficult to establish without a renal biopsy confirmation. However, other embolic signs may be used to reach a presumptive diagnosis. In our patient, the presence of Hollenhorst plaques in the retina with the recent history of aortic surgery was thus diagnostic of atheroembolic renal disease. Blue toe syndrome may be the sole dermatological manifestation of atheroembolic renal disease. Hollenhorst plaques in the retina may aid in the diagnosis. Conflict of interest statement. None declared.

Graph theory methods were used to analyze the topology of the renal glomerular capillary network using data both from a serial reconstruction of a rat glomerulus and from the literature. The graphs obtained were tested for planarity, and all but one were found to be nonplanar. This result indicated that the development of the glomerular capillary network must include a nonplanar growth process, and new growth models were proposed. In addition, the statistical properties of capillary branching patterns were analyzed, and a node degree distribution function estimate was obtained.

Effect of variations in dietary sodium intake on sodium excretion in mature rats. Sprague-Dawley rats weighing 400g or more were studied to determine whether their continued weight gain affects renal sodium handling. Rats maintained on a wide range of sodium intakes gained 3.9 ± 0.4 g/day. The intercept of a linear regression of intake against urinary excretion provided an estimate of the minimum daily requirement for sodium intake of 247 ±33 µEq/day. When more than this required amount was ingested, the animals excreted the excess quantitatively in the urine. When less was ingested they continued to gain weight at a slower rate, 1.6 ± 0.6 g/day, and remained in positive sodium balance. Nonetheless, they developed a sodium deficit manifested as retention of a sodium challenge. Thus, on an adequate dietary intake the normal physiological state of Sprague-Dawley rats of this size is one of chronic sodium retention rather than neutral sodium balance. In contrast, when inadequate sodium is ingested a deficit develops in the absence of external losses. These observations have important implications for the interpretation of studies of renal sodium handling in these animals.Effet de variations de l'apport sodé alimentaire sur l'excrétion sodique de rats matures. Des rats Sprague-Dawley pesant 400g ou plus ont été étudiés pour déterminer si leur prise de poids continue affecte l'élimination sodée rénale. Des rats maintenus à des apports sodés très variés gagnaient 3,9 ± 0,4 g/jour. L'interception de la régression linéaire de l'apport en fonction de l'excrétion sodée fournissait une estimation de l'apport quotidien minimum nécessaire en sodium, 247 ± 33 µEq/jour. Lorsque plus que cette quantité nécessaire était ingéré, les animaux excrétaient quantitativement cet excès dans les urines. Lorsqu'ils ingéraient moins, ils continuaient à prendre du poids plus lentement, 1,6 ± 0,6 g/jour, et restaient en balance sodée positive. Néanmoins, ils développaient un déficit sodé se manifestant par la rétention d'une surcharge sodée. Ainsi, lors d'un apport alimentaire adéquat, l'état physiologique normal des rats Sprague-Dawley de cette taille est une rétention chronique du sodium, plus qu'une balance sodée neutre. A l'opposé, lorsqu'insuffisamment de sodium est ingéré, un déficit se développe en l'absence de pertes externes. Ces observations ont des implications importantes pour l'interprétation des études de l'élimination rénale du sodium chez ces animaux.

Glucose and glycerol compared as osmotic agents for peritoneal dialysis. The potential utility of glycerol as an osmotic agent for peritoneal dialysis was evaluated by conducting both isosmotic and hyperosmotic exchanges in anesthetized rats. Similar exchanges were conducted using glucose, and the results with the two agents were compared. During hyperosmotic exchanges both agents produced significant osmotic flow of water, but at initial molar concentrations that were equal the flow observed with glycerol was nearly 40% less than that observed with glucose. The lower volume transport generated by glycerol was found to be due to its surprisingly rapid removal from peritoneal fluid when it was present at hyperosmotic concentrations, but paradoxically during isosmotic exchanges, when its concentration was low, glycerol was absorbed only slightly faster than glucose. The observed increase in peritoneal permeability when glycerol was used resulted in a twofold increase in the caloric load imposed per unit of water removed in comparison with glucose. Le glucose et le glycerol compare comme agents osmotiques pour la dialyse peritoneale. L'utilite potentielle du glycerol comme agent osmotique pour la dialyse peritoneale a ete evaluee en effectuant des echanges isosmotiques et hyperosmotiques chez des rats anesthesies. Des echanges similaires ont ete faits en utilisant du glucose, et les resultats avec les deux agents ont ete compares. Pendant les echanges hyperosmotiques, les deux agents produisaient un flux d'eau osmotique significatif, mais aux concentrations molaires initiales qui etaient identiques, le flux observe avec le glycerol etait environ 40% moindre que celui observe avec le glucose. Il a ete trouve que le plus faible volume de transport genere par le glycerol etait du a sa disparition etonnament rapide du fluide peritoneal lorsqu'il etait present a des concentrations hyperosmotiques mais, paradoxalement, pendant les echanges isosmotiques, lorsque sa concentration etait faible, le glycerol n'etait absorbe que legerement plus vite que le glucose. L'augmentation observee de la permeabilite peritoneale lorsque le glycerol etait utilise a entraine une augmentation de deux fois de la charge calorique imposee par unite d'eau enlevee en comparaison avec le glucose.

1. Proximal tubular fluid flow rate was deliberately reduced to control values in rats after acute volume expansion with hyperoncotic albumin, to determine if the depression of reabsorption by albumin-induced expansion could be uncovered by preventing the associated increase in filtrate delivery. Tubular fluid flow was reduced either by reducing renal perfusion pressures or by diverting fluid from early proximal tubular sites. 2. In the absence of controlled delivery, expansion with hyperoncotic albumin increased nephron filtration rate, reduced the TF/P inulin ratio, but had no effect on absolute reabsorptive rate. When proximal tubular flow rate was returned to control values by a simultaneous early collection, fractional reabsorption remained depressed. By contrast, when tubular flow was maintained at control values by reducing renal perfusion pressure, the large fall in fractional reabsorption was blocked. 3. The results indicate that expansion with hyperoncotic albumin depresses proximal tubular reabsorption independently of delivery rate into the proximal tubule, but that this effect can be reversed by a reduction in renal perfusion pressure. These observations unify the results of previous studies and indicate the presence of a delivery-related influence on proximal reabsorption. The inability to detect a reduction in absolute reabsorption when nephron filtration rate is increased during expansion with hyperoncotic albumin is probably due to the countervailing influence of increased delivery rate, which raised reabsorptive rate.

In the present study, a low-compliance passive pressure transducer and a microprocessor-based data acquisition system were used to obtain recordings of time-varying blood pressure in the femoral arteries of anesthesized rats. Discrete spectral analysis techniques were used to analyze the pressure-time records and to quantify the contributions to the arterial pressure profile of frequencies in the band from 0 to 128 Hz. In accordance with previous studies in other species, most of the energy in the spectra obtained was concentrated in narrow bands corresponding to harmonics of the cardiac and respiratory cycles. The spectra also provided evidence consistent with either an autoregressive component or an ultra-low-frequency blood pressure rhythm of unidentified origin, but did not indicate the presence of either Traube-Hering or splenic "waves" in the arterial system of the rat.

In many previous studies, the natriuresis induced by saline loading has been demonstrated to persist even though glomerular filtration rate (GFR) has been decreased to below pre-expansion levels by a reduction in renal artery pressure. In such studies, however, the kidney has been exposed to the effects of volume expansion for varying periods of time before renal artery pressure was controlled. The present experiments were designed to evaluate whether this period of exposure induces critical changes in intrarenal factors that are responsible for the natriuresis. Experiments were carried out in rats, in which renal artery pressure was decreased to 70 mm Hg either at the onset of saline loading (immediate clamping experiments) or after 45 min of saline loading had elapsed (delayed clamping experiments). In the delayed clamping experiments, consonant with previous studies, mean sodium excretion, 3.2 μeq/min, remained markedly increased above control, despite a reduction in GFR to 91% of the hydropenic control value. In contrast, when renal artery pressure was comparably reduced at the onset of saline loading mean sodium excretion was only trivially increased, 0.4 μeq/min, although GFR increased to 140% of the hydropenic control value. These results exclude an important role for either a circulating hormone or a reduction in plasma oncotic pressure in the natriuretic response to saline loading, and indicate that intrarenal factors are the critical determinants of the natriuresis. We have used the difference in response to saline loading in the immediate and delayed clamping experiments to evaluate the role of two intrarenal factors, interstitial hydrostatic pressure and renal plasma flow. Interstitial pressure changes were estimated from changes in tubular pressure and diameter by using the in situ compliance characteristics of the tubules. In a group of rats saline loaded without aortic clamping, interstitial pressure increased by 4-5 mm Hg and renal plasma flow increased by 2.5 ml/min. During the period of reduced renal artery pressure, however, neither interstitial pressure nor renal plasma flow was detectably increased above control in either the immediate or the delayed clamping experiments. The only noteworthy difference between the experiments in which a natriuresis occurred (unclamped and delayed clamping studies) and the experiments in which no natriuresis occurred is that in the former group the kidney was at least transiently exposed both to an increase in renal plasma flow and interstitial pressure. These findings indicate, first, that extracellular fluid volume expansion can induce a natriuresis only if the kidney has been exposed to at least a transient increase in either interstitial hydrostatic pressure or renal plasma flow (or both); and, second, that a sustained increase in interstitial pressure and renal plasma flow is not required for the natriuresis to persist.

Modifications of existing methods permit accurate measurements of the iron content of tissue specimens.

A case is reported of a patient with intussusception complicating tropical sprue demonstrable over a period of months. There was clinical and laboratory evidence of malabsorption. The chronicity of tropical sprue and its delayed laboratory and histologic response to therapy was demonstrated. Such a case has not been previously reported.

In four patients with pre-existing proliferative glomerulonephritis and the nephrotic syndrome allergic interstitial nephritis developed that resulted in moderate to severe, but reversible, renal failure. In three of these patients clinical evidence for a hypersensitivity reaction was present. In all cases renal biopsy revealed a diffuse interstitial infiltrate containing many eosinophils. Cessation of furosemide or thiazides, coupled with the institution of prednisone therapy, was followed by dramatic improvement of renal function. None of the known causes of interstitial nephritis were detected. Although a definite etiologic relation has not been established, the diuretic agents employed may have been responsible for the interstitial nephritis in these cases.

Micropuncture studies were carried out in the rat to evaluate the in situ distensibility characteristics of the proximal and distal tubules under a variety of experimental conditions. In the first phase, we determined the response of tubular diameter (D) to changes in tubular pressure (P) induced by partially obstructing single tubules. The response observed under these conditions (i.e., when interstitial pressure is presumed to be constant) has been defined as the compliance of the tubule. Over the range of tubular pressures studied (10-35 mm Hg for the proximal tubule, 5-25 mm Hg for the distal tubule) the compliance characteristics of the proximal and distal tubule were found to be markedly different; the proximal tubular pressure-diameter relationship was linear, DeltaD/DeltaP = 0.45 mum/mm Hg, whereas the distal pressure-diameter relationship was curvilinear, DeltaD/DeltaP = c(-0.1xP+2.2). In the second phase we used the compliance data to construct a series of theoretical pressure-diameter curves that define the response of the tubule to increments in interstitial as well as intratubular pressure. These curves indicate that changes in distal diameter should provide a sensitive index of a rise in interstitial pressure under conditions in which the transtubular pressure gradient is increased by a small amount, but that proximal diameter should provide a more sensitive index of changes in interstitial pressure when the transtubular pressure gradient is increased by a large amount. In subsequent experiments in which furosemide was administered, we observed that the pressure-diameter relationships for both the proximal and distal tubule were indistinguishable from the compliance curves, a finding consistent with the interpretation that interstitial pressure was not appreciably changed from control. By contrast, when mannitol was administered, both proximal and distal tubular pressure-diameter relationships were significantly altered in a fashion consistent with a large increase in interstitial pressure. Neither with furosemide nor mannitol administration did it appear likely that significant changes in tubular compliance could account for the observed behavior of the tubule.Finally, we propose that a knowledge of tubular compliance will be useful in exploring the interrelationships between tubular and peritubular pressures, tubular anatomy, and transtubular ionic permeability. Recent studies linking changes in the geometry of lateral intercellular spaces of the tubule to changes in passive ion movement suggest that an investigation of such anatomical-functional correlates should be productive.

The use of polyelectrolytes as osmotic agents for peritoneal dialysis. Various small and large molecules have been studied as osmotic agents to replace dextrose in peritoneal dialysis. Macromolecules are attractive because of their slow absorption from intraperitoneal solutions; however, it has been assumed that they are only marginally effective as osmotic agents unless they function as polyelectrolytes at physiological pH. In experimental exchanges conducted in rats we measured volume changes induced by Gelifundol (5.5% oxypolygelatin) and Ringers lactate to which was added either nothing, 4.25% dextrose, or 5% albumin. In the control exchanges using Ringers lactate, intraperitoneal fluid volume remained unchanged for eight hours. The volume changes induced by 4.25% dextrose were complete within two hours and resulted in a two-thirds increase over the amount of fluid administered. In both series in which polyelectrolytes were used volume transport was sustained throughout an eight hour dwell. With 5% albumin the total increase in fluid volume was about 40% of that installed, while Gelifundol caused fluid volume to double. Qualitatively similar results were obtained in transport studies conducted in vitro. Physical studies of the oxypolygelatin solutions indicated that the fixed charges per liter were comparable to those in the albumin solutions. Thus the different volume transport the two proteins induced could not be attributed to Donnan effects. However, since the molecular weight of albumin is triple that of Gelifundol the van't Hoff pressures of the two macromolecules can explain the observed differences in volume transport. These results suggest that neutral macromolecules deserve further study as potential osmotic agents for peritoneal dialysis.

This paper presents the results of a CAPD program, which provides care to an underpriviliged, inner-city population. Serious medical and psychosocial problems did not interfere with training and did not produce an unusually high drop-out rate. However, we encountered a high incidence of infection. The success of such a program demonstrates that traditional criteria for CAPD patient selection are not universally applicable.

A patient who presented with hypertension of recent onset was found to have unilateral hydronephrosis. Increased activity of the renin-angiotensin system was documented with renal-vein-renin concentrations. The hydronephrosis was due to a primary transitional cell carcinoma of the ureter. Following nephroureterectomy, blood pressure returned to normal and has remained so for two years.

THE GREEKS did it with hemlock, as immortalized by Socrates. The ancient physician, Galen, devoted himself to the perfection of Theriac, the universal antidote, composed of more than seventy ingredients, including viper's flesh. Poisoning is as old as the human condition; only patterns of drug use and treatment of poisoning have changed with time. While twenty years ago aspirin and barbiturates were leading causes of serious intoxication, today antidepressants, tranquilizers, and acetaminophen have taken the lead. Narcotics are an age-old source of drug intoxication and remain a major problem today. The majority of drug poisoning documentations are made through emergency room (ER) visits. The statistics available for 1981 from the Drug Abuse Warning Network (DAWN) of the National Institute on Drug Abuse l reveal that 1 out of every 166 ER visits was due to drug intoxication. Table 1 lists the ten drugs (or drug groups) most frequently mentioned by ERs in the DAWN survey. The statistics for each drug include the frequency with which it was mentioned by ERs, expressed as a percentage of total ER visits; admissions to the hospital as a percentage of ER mentions of the drug; and medical examiner mentions of the drug as a percentage of total deaths. Of note is the frequency with which drugs were taken in combination with ethanol or other drugs-46 % of ER visits and 63 % of deaths involved multiple drugs. For the benzodiazepines, in particular, over 70% of the ER mentions included another drug (ethanol half the time) and over 90 % of medical examiners mentions included at least one other drug. In fact, death rarely occurs from the ingestion (versus intravenous use) of benzodiazepines alone. Approximately 40% of drug-related cases required admission to the hospital, but less than 2.3% resulted in death (if narcotics and patients dead-on-arrival are excluded, the figure is 1.1 %). These impressive statistics on survival are relatively new. The mortality rate from drug overdose was over 20% as recently as 25 to 30 years ago, when CNS stimulation was the crux of therapy. Drugs such as pentylenetetrazol, picrotoxin, and amphetamines were considered essential and were not readily abandoned. 2.3 Even with reported increased incidences of seizures, cardiac arrhythmias, and vomiting, it took many years to recognize that mortality statistics were, in fact, worse with this aggressive intervention. 4.5 The first major step toward improvement of outcome resulted from lessons learned in the treatment of shock on the battlefields of World War II and applied by Kirkegaard6 to show the importance of circulatory collapse in intoxication. In addition, in 1951, Nilsson7 established the importance of a clear and patent airway and prevention of hypoxia. The final leap in patient care came in 1961 when Clemmesen and Nilsson8 demonstrated systematically from 12 years experience in Copenhagen averaging more than 1,500 cases of poisoning per year, that intensive supportive therapy, without massive gastric lavage or analeptic agents, resulted in mortality rates of 1.5 %. Acceptance of their "Scandinavian Method," as it came to be known, and abandonment of analeptic therapy has led to the excellent mortality statistics seen today. It is toward the small group of patients who fail to respond to intensive supportive care that treatment innovations, especially extracorporeal therapy, have been directed. The rationale for extracorporeal treatment is straightforward: since poisons achieve their toxic effect on target organs via the blood stream, their elimination from the blood should result in amelioration of the patient's condition. Forced diuresis was used to accelerate elimination, but with the advent of technology for hemodialysis, direct access to and removal of poisons from the circulation became a possibility. The development of hemoperfusion permitted even more effective removal of substances from the blood. Although the pur

To clarify the association between proteinuria and congestive heart failure (CHF), 24-hour urinary protein determinations were obtained from 27 patients with objectively documented CHF, before and after therapy of the CHF. The results demonstrate that modest proteinuria is a frequent feature of CHF and that this proteinuria reverses promptly with successful CHF therapy. Proteinuria exceeding 500 mg/day occurred only in patients with acute pulmonary edema. However, there was no other correlation between severity of proteinuria and type or chronicity of CHF. When proteinuria exceeds 1 g/24 h or when proteinuria does not reverse within 2 weeks of successful CHF therapy, intrinsic renal disease should be suspected.

Endotoxin caused marked abnormalities in iron absorption and metabolism within hours after the administration of a parenteral dose. The changes observed during the 1st day following injection were unique; there was decreased absorption of iron with a normal intestinal iron content, an accelerated rate of clearance of iron from plasma, and a decreased serum iron concentration. That a generalized cytotoxic effect upon the gut was not the cause of these changes was suggested by the normal intestinal histology and lifespan of mucosal cells, normal absorption of glucose and unchanged excessive absorption of iron by iron-depleted, endotoxin-treated animals. Two days after the administration of endotoxin most abnormalities became normal except that the intestinal iron content increased, and a significant decrease in iron absorption persisted. It was only during this later period that iron-depleted rats had decreased absorption of iron from the gut. It was postulated that the acute absorptive defect was caused by a decreased capability to transfer iron from the mucosal cell into the body, whereas the late defect was associated with impaired entry of intraluminal iron into the intestinal absorptive cells.