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In a retrospective study of the effect of treatment in biopsy-proved idiopathic membranous nephropathy, 91 adults and 12 children were followed for periods up to 29 years after clinical onset (mean, 6.5 years). Forty-four were treated with corticosteroids, 15 with corticosteroids and immunosuppressants; 44 had no treatment and served as a control group. Clinical cure and improvement were significantly greater in the treated than in the nontreated group (P less than 0.01). The recurrence rate, occurrence of renal failure and probability of death were significantly greater in the nontreated group, although some of these patients eventually showed improvement. Prognosis was better in patients who responded to therapy. These data strongly suggest that steroid therapy is beneficial in patients with membranous nephropathy.

We examined in anesthetized dogs the effects of left (L) intrarenal artery infusion of angiotensin II (AII) on renal hemodynamics, urinary concentration and Na excretion, and papillary plasma flow (PPF) (measured by the albumin accumulation technique) in both kidneys. Following AII infusion (0.5 ng/kg/min) into the L renal artery, urinary Na excretion decreased and osmolality increased slightly ipsilaterally, whereas Na excretion did not change significantly and osmolality decreased in the right (R) kidney. PPF was significantly lower in the L compared to the R kidney. When saline loading was superimposed on L intrarenal AII infusion, there was a blunted natriuretic response ipsilaterally with a significantly smaller decrease in urine osmolality compared with the R kidney. PPF increased significantly in the R, but not in the L kidney. Finally, AII blockade with saralasin prior to AII infusion and saline loading prevented the differences between the two kidneys, including PPF. In all groups GFR and renal blood flow did not differ between the two kidneys before or after AII. These data suggest that AII regulates regional blood flow in the medulla, and that the exogenously administered AII induces papillary ischemia, which serves to preserve medullary hypertonicity, preventing an increase in PPF during saline loading, and possibly contributing to the diminished natriuretic response.

A patient with a single functioning kidney and anuria due to ureteropelvic obstruction by a Candida fungus ball is described. During treatment with amphotericin B administered via a nephrostomy tube the drug was not detected in the serum, indicating that absorption from urothelium was not significant. Immunological studies demonstrated a lack of cell-mediated immunity which was probably brought about by a long course of prednisone and later restored when this drug was discontinued. This immunosuppression was evident even with a relatively small dosage of prednisone (5 mg daily). The literature concerning renal candidiasis and predisposing factors is reviewed.

In order to assess the renal tubular site(s) at which sodium reabsorption is enhanced in chronic sodium-depletion, seven normal dogs, six salt-depleted dogs, and three normal dogs receiving aldosterone were studied during a steady-state water diuresis under Pentothal anesthesia and during progressive hypotonic saline diuresis. For both maintenance of the water diuresis and progressive hypotonic saline diuresis 0.45% NaCl was used. During the steady state water diuresis delivery of sodium to the diluting segment of the nephron as approximated by solute-free water clearance + sodium clearance/glomerular filtration rate (CH2O + CNa/GFR) was significantly lower in salt-depleted dogs compared to normal dogs with or without aldosterone. During progressive hypotonic saline infusion fractional free water excretion (CH2O/GFR) was similar in all three groups as CH2O + CNa/GFR increased up to 12-14 ml/min-100 ml GFR. Thereafter, CH2O/GFR continued to rise in virtually a straight line in salt-depleted dogs but leveled off in normal dogs with or without aldosterone. These data demonstrate that enhanced sodium reabsorption in the diluting segment of the nephron is an important determinant of the renal sodium retention in chronic extracellular volume contraction in dogs in addition to confirming the presence of increased proximal tubule sodium reabsorption in these animals.

In an attempt to examine the effects of mild and severe chronic metabolic acidosis on proximal tubule sodium reabsorption, 6 dogs were given 10 mEq. per kilogram per day and 5 dogs were given 20mEq. per kilogram per day of ammonium chloride for 3 days and compared to 12 normal dogs during a steady-state water diuresis and following the administration of ethacrynic acid (EA) intravenously (2 mg. per kilogram) utilizing standard clearance methodology, In the severely acidotic group (pH decrease is greater tthan 0.2) plasma pH was 7.08 +/- 0.06 and plasma bicarbonate was 6.3 +/- 1.0 Eq. per liter compared to a pH of 7.33 +/-0.02 and bicarbonate of 13.4 +/- 0.7 in mild acidosis (pH decrease is less than 0.2). During a steady-state water diuresis urine flow was 14.2 +/- 0.9 in severely acidotic compared to 10.5 +/-0.7 ml. per minute per 100 ml. glomerular filtration rate (GFR) in normal dogs (p is less than 0.01). Following EA sodium clearance increased 38.4 +/- 3.5 in severely acidotic dogs and 27.6 +/- 2.0 ml. per minute per 100 ml. GFR in normal dogs (p is less than 0.02). In mild acidosis, steady-state fractional urine flow and the increase in fractional sodium clearance following EA were not significantly different than normal dogs. We conclude that chronic metabolic acidosis leads to an increase in distal solute load and enhanced natriuretic effect of EA secondary to a decrease in proximal tubule sodium reabsorption which may be dependent upon the degree of reduction in the plasma bicarbonate level.

To evaluate the use of the activated partial thromboplastin time (APTT), as measured by the Coag-A-Mate semi-automatic unit, in lowering the dosage of heparin in stable chronic hemodialysis patients, four protocols for anticoagulation were utilized. Ten patients were dialyzed five times with each protocol. In protocol I, clotting time was performed baseline, 2 and 4 hours and in protocol II, baseline and every 30 minutes, with heparin administered by bolus to keep the clotting time at 2-2 1/2 times normal. In protocols III and IV the APTT was performed every 30 minutes, with heparin given by bolus in protocol III and infusion in protocol IV, to keep the APTT 1 1/2-2 times normal. Protocol I required 6000 +/- 543 U of heparin with the dose decreasing significantly to 3694 +/- 158 U in protocol II, 2634 +/- 139 U in protocol III and 2013 +/- 117 U in protocol IV (P less than 0.05- less than 0.001). Three episodes of clotting occurred, one in protocol III and two in protocol IV. There was no bleeding, and clearances of urea, creatinine, phosphate and uric acid at 1 and 5 hours were similar in all protocols. APTT, as measured by the Coag-A-Mate unit, provides a simple means of lowering heparin requirements in routine dialysis patients.

Three patients are reported who presented with severe oliguric renal failure due to retroperitoneal fibrosis and obstructive uropathy in whom spontaneous diuresis and recovery of renal function took place, a course resembling acute tubular necrosis. There were, however, several clinical and laboratory findings that provided clues to the presence of obstructive uropathy. Two of the three patients had low back or abdominal pain. All three patients presented with anemia and significant hyperkalemic, hyperchloremic metabolic acidosis with only a small increase in anion gap and two of the patients had an inappropriately high urine pH. Neither tubular cell casts nor pigmented granular casts were identified in the urine in any of the patients. In all three patients the urine output increased from oliguric levels to 1400 - 2000 ml/day within 1 day associated with rapidly improving renal function. This report demonstrates and reinforces the need to rule out obstruction in all patients with renal failure of unknown etiology and adds retroperitoneal fibrosis to the list of diseases associated with renal failure and spontaneous recovery.

The clinical patterns of acute renal failure have changed in the past 10 to 15 years. Nonoliguric acute tubular necrosis has become more common, as has nephrotoxic acute tubular necrosis. Other syndromes that have increased in incidence are acute tubular necrosis secondary to rhabdomyolysis and acute renal failure secondary to nonsteroidal anti-inflammatory drugs. Calculation of the fractional sodium excretion or the renal failure index helps distinguish between prerenal azotemia and acute tubular necrosis. In a significant number of patients with acute renal failure, a kidney biopsy may be necessary to establish the correct diagnosis and initiate the appropriate therapy.

In a previous prospective study, we reported that infusion intravenous pyelography (IVP) in 40 patients with chronic renal insufficiency resulted in acute renal failure (ARF) in 28 patients (70%). In an attempt to prevent this complication, we have evaluated the conditions of another group of 37 patients with chronic renal insufficiency treated in a similar manner except that each patient received 250 mL of 20% mannitol 60 minutes after infusion of the IVP dye (diatrizoate sodium, 300 mL of a 30% solution). These patients were similar to those in the previous study with regard to age, sex, renal function, and incidence of diabetes. Only eight (22%) of the 37 patients had ARF develop after infusion IVP in this study. This incidence was significantly lower compared with 70% in the previous study. We conclude that administration of hypertonic mannitol 60 minutes after administration of the radiographic contrast material is highly effective in preventing ARF after infusion IVP in patients with chronic renal insufficiency.

Acute renal failure (ARF) following infusion intravenous pyelography (IVP) has been reported in patients with chronic renal insufficiency, particularly diabetics. Renal function was evaluated before and after infusion IVP in 40 patients with chronic renal insufficiency. In 11 of 12 (92%) diabetics and 17 of 28 (61%) nondiabetics, a 25% or greater increase in serum creatinine values and/or decrease in creatinine clearance was noted after IVP despite adequate hydration in all patients. The maximum decrease in kidney function occurred within three days and usually returned to or near pre-IVP levels in seven to ten days. At least 70% of the patients had hypertension and/or evidence of vascular disease. The data suggest that preexisting vascular disease in the kidney, possibly associated with the known vasoconstricting effects of contrast media, may be an important factor in the ARF following infusion IVP.

The alpha-adrenergic blocking agent phenoxybenzamine (PBA) was administered intravenously (10 mug kg-1 min-1) during a steady state water diuresis under pentothal anesthesia to six normal dogs, six dogs with chronic throacic inferior vena cava constriction and ascites (caval dogs) and seven dogs chronically salt depleted by sodium restriction and furosemide administration. In normal dogs urinary sodium excretion increased significantly from 265+/56 (SEM) to 370+/65 muequiv./min, whereas no increase in sodium excretion was noted in either caval dogs or salt depleted animals after PBA. In all three groups urine volume, fractional free water clearance and distalsodium load did not change significantly. In normal dogs, tubular sodium reabsorption decreased significantly from 73.4+/2.8% to 63.1+/4.0%, whereas no change was noted in caval or salt depleted dogs. Blood pressure and renal hemodynamics were not significantly altered by PBA administration in any group. These data demonstrate a natriuretic effect of alpha-adrenergic blockade in normal dogs with the major effect in the water clearing segment of the nephron. The absence of any effect in chronic caval or salt depleted dogs suggests that increased alpha-adrenergic activity does not play a significant role in the sodium retention of these animals.

Chronic hemofiltration as a treatment for end stage renal disease has been shown to have several advantages over standard hemodialysis including: improvement in well being, increased strength, decrease in hypotensive episodes during treatment and decrease in the degree of hypertension between treatments. The major drawback of hemofiltration as practiced today is the need to replace the large quantities of ultrafiltrate formed with sterile, pyrogen-free replacement solution. We have solved this problem by passing the ultrafiltrate through a sterile REDY Sorbent Cartridge to remove urea, creatinine and "uremic toxins" prior to returning it to the patient via a closed system. We have called this system SRUF for Sorbent Recycling of Ultrafiltrate and have carried out an A-B-A, B-A-B cross-over study (15 week periods) comparing SRUF with standard hemodialysis in 8 ESRD patients previously treated with hemodialysis. Clinical and laboratory parameters measured included: hemoglobin, hematocrit, blood transfusion requirement, electrolytes, aluminum levels, liver function tests, enzymes, lipids, glucose, cardiac function studies, weight, blood pressure, urea generation, urea space, incidence of hypotension and muscle cramps, and questionnaires on well being. The results of these studies can be summarized as follows: SRUF can be performed by the hemodialysis staff as a routine, outpatient procedure for ESRD patients utilizing the machinery and tubing developed as part of this protocol. SRUF, when used as a chronic treatment for ESRD patients, has no deleterious effects and is associated with many of the same benefits ascribed to routine hemofiltration, including improvement in well being, decrease in cramping and decrease in symptomatic hypotension during treatment as compared to hemodialysis.(ABSTRACT TRUNCATED AT 250 WORDS)

Renal biopsies of 23 heroin addicts who presented with the nephrotic syndrome were examined by light and electron microscopy. The majority of patients (14) showed focal segmental glomerular sclerosis on light microscopy, four patients showed "minimal change", and two were classified as "focal global sclerosis." In one case focal mesangial proliferation was the outstanding feature; one patient had diabetic glomerulosclerosis; and one had mesangiocapillary glomerulonephritis and dysproteinemia. Visceral epithelial swelling and proliferation were present in 14 patients on light on light microscopy. Electron microscopy showed distinct podocyte changes consisting of loss of foot processes, vacuolization, and cytoplasmic degeneration; focal separation of podocytes from basement membranes was found in 11 of 18 cases. In some instances a few electron-dense deposits were present in the mesangium. Membranous nephropathy was not encountered, although it occurs in 30 to 40% of unselected adult nephrotic individuals. Of 15 patients followed for 2 months to 5 years, one died of heroin overdose, eight went into renal failure, two improved, and four continued to have proteinuria. It is concluded that nephrotic syndrome of heroin addicts is most often associated with focal segmental glomerular sclerosis and occasionally with minimal change disease or focal global sclerosis. Conceivably these three conditions represent different phases of one disease process, although different reactions to heroin or its various vehicles and contaminants cannot be excluded. The morphologic resemblance to experimental aminonucleoside and N,N'-diacetylbenzidine-induced nephrosis suggests a possible toxic origin.

To investigate the role of medullary hemodynamics and vasoactive hormones in sodium retention in dogs with aortocaval fistula, we examined papillary plasma flow (PPF), solute content, and renal output of renin, norepinephrine, and prostaglandin E2 (PGE2) in anesthetized normal and fistula dogs. During hydropenia, cardiac output was elevated and systemic vascular resistance reduced in fistula dogs, accompanied by markedly increased renal output of renin, norepinephrine, and PGE2. In fistula dogs the blunted diuretic and natriuretic response to saline loading was not due to impaired myocardial contractility. During hydropenia and after saline loading, glomerular filtration rate (GFR) and renal blood flow were similar in normal and in fistula dogs; however, PPF was significantly lower in fistula dogs, accompanied by significantly greater papillary tissue osmolality and sodium content. These findings indicate that in fistula dogs enhanced medullary sodium reabsorption is associated with decreased PPF and stimulation of the renin-angiotensin and adrenergic nervous system. Furthermore, the reduced PPF obviates medullary solute washout during saline loading, and may contribute to the blunted diuretic and natriuretic response.

The unique architecture and organization of medullary vasculature permit regional regulation of medullary hemodynamics by vasoactive hormones and are conducive to the operation of the countercurrent multiplication system. Recent studies suggest that an increase in inner medullary blood flow causes medullary solute washout, which in turn decreases passive sodium transport in the thin ascending limb of Henle's loop. In canine models of chronic sodium retention accompanied by activation of the renin-angiotensin system, glomerular filtration rate (GFR), renal blood flow (RBF), and intracortical blood flow distribution were similar to those in normal dogs; however, papillary plasma flow (PPF) was markedly reduced and papillary tissue solute content was increased significantly both during hydropenia and after saline loading. During euvolemic diuresis with loop diuretics, there was an increased renin release associated with a marked reduction in PPF, despite an increase in total RBF. Direct intrarenal infusion of angiotensin II (AngII) (at a dose not affecting GFR and RBF) induced ipsilateral sodium retention, conservation of urinary concentration, and papillary ischemia. These studies provide evidence for regional regulation of medullary hemodynamics by AngII, possibly contributing to sodium retention in chronic salt-retaining states.

Hypertension is very common in the elderly patient with renal insufficiency and may be primary or secondary to the kidney disease. In these patients, hypertension is usually associated with an increase in peripheral vascular resistance and salt sensitivity (the latter related to the degree of renal failure.) Therapy should be tailored to the individual patient, particularly when the elevated blood pressure and renal insufficiency are associated with other significant medical problems. Most of the drugs used in younger hypertensives may be used in the elderly patient with renal insufficiency, but in general, starting and maintenance doses should be lower because of the greater sensitivity due to age and/or the renal failure. The goal in the elderly hypertensive patient with renal failure is similar to that in other hypertensive patients: blood pressure should be brought to 140/90 mm Hg or lower. In the elderly patient with resistant hypertension or who manifests a decrease in kidney function as blood pressure is lowered, an effort must be made to look for associated renovascular disease.

The effects of intravenous administration of angiotensin II on renal water and electrolyte excretion were examined during hydropenia, water diuresis, and hypotonic saline diuresis in anesthetized normal dogs and dogs with thoracic inferior vena cava constriction and ascites (caval dogs). The effects of unilateral renal artery infusion of a subpressor dose were also examined.During hydropenia angiotensin produced a decrease in tubular sodium reabsorption, with a considerably greater natriuresis in caval dogs, and associated with a decrease in free water reabsorption (T(c) (H(2)O)). Water and hypotonic saline diuresis resulted in an augmented angiotensin natriuresis, with a greater effect still observed in caval dogs. In these experiments free water excretion (C(H(2)O)) was limited to 8-10% of the glomerular filtration rate (GFR), although distal sodium load increased in every instance. In the renal artery infusion experiments a significant ipsilateral decrease in tubular sodium reabsorption was induced, particularly in caval dogs.These findings indicate that angiotensin has a direct effect on renal sodium reabsorption unrelated to a systemic circulatory alteration. The attenuation or prevention of the falls in GFR and effective renal plasma flow (ERPF) usually induced by angiotensin may partially account for the greater natriuretic response in caval dogs and the augmentation during water or hypotonic saline diuresis. However, a correlation between renal hemodynamics and the degree of natriuresis induced was not always present and, furthermore, GFR and ERPF decreased significantly during the intrarenal artery infusion experiments. Therefore, the present experiments indicate that another mechanism is operative in the control of the angiotensin natriuresis and suggest that alterations in intrarenal hemodynamics may play a role.The decrease in T(c) (H(2)O) and the apparent limitation of C(H(2)O) associated with an increase in distal sodium load localize the site of action of angiotensin to the ascending limb of Henle's loop and the proximal tubule.

The effects of water diuresis, hypotonic NaCl, and hypotonic mannitol diuresis on renal sodium and water excretion were examined in normal dogs and in dogs with chronic constriction of the thoracic inferior vena cava and ascites (caval dogs). During all three diuretic states, the capacity to excrete solute-free water relative to the supply of sodium to the water clearing segment of the nephron was significantly greater in the caval dog. This finding was most evident during hypotonic NaCl diuresis but was also striking during hypotonic mannitol diuresis despite the more unfavorable gradient for sodium reabsorption at the distal tubule produced by this agent in caval dogs. In addition, fractional distal sodium load was significantly smaller in caval dogs during water diuresis and could not be increased as readily as in normal dogs by hypotonic NaCl or mannitol infusion. The data indicate that fractional sodium reabsorption is increased at the water clearing segment and the proximal tubule in caval dogs. The differences in the pattern of free water clearance and tubular sodium transport between normal and caval dogs could not be easily explained by alterations in renal hemodynamics or aldosterone secretion. It is suggested that in the caval dog an alteration occurs in other factors which might influence renal tubular sodium transport, such as intrarenal hemodynamics, renal interstitial volume or pressure, or a natriuretic hormone, leading to increased tubular sodium reabsorption.