Immune-complex nephritis in bacterial endocarditis.

Glomerulonephritis developed in a 42-year-old man with subacute bacterial endocarditis caused by an alpha-hemolytic Streptococcus. The patient showed hypocomplementemia and an elevated serum rheumatoid factor titer. Immunofluorescence microscopy of a renal biopsy specimen demonstrated granular deposits of IgM and C3 in all glomeruli studied. With the indirect immunofluores(ence technique and specific antiserum, the antigen in glomerular deposits was observed to correspond to the organism found in the blood cultures. These findings can be taken as further evidence that the glomerulonephritis of subacute bacterial enoocarditis represent an immune-complex disease.

Hyporeninemic hypoaldosteronism after chronic sodium bicarbonate abuse.

We describe a 52-year-old man who, following the discontinuation of massive intake of sodium bicarbonate, in the absence of renal insufficiency, developed progressive hyperkalemia and hyponatremia in association with hyporeninemic hypoaldosteronism. The mechanism of this syndrome is not known, but may involve suppression of the renin-angiotensin-aldosterone axis by chronic volume expansion.

Erythrocytosis associated with the nephrotic syndrome.

A 23-year-old-man had true erythrocytosis and the nephrotic syndrome. A renal biopsy specimen showed focal sclerosing glomerulonephritis and nephrosclerosis. Both serum and urinary erythropoietin levels were increased, and plasma renin activity was in the high normal range. The association of erythrocytosis and glomerulonephritis with the nephrotic syndrome is reviewed, and the uniqueness of this association is proposed. Finally, a dissociation between these hormones was demonstrated using water immersion to the peck as a suppressive maneuver.

Potassium homeostasis in chronic diabetes mellitus.

Potassium homeostasis was evaluated in 13 patients with diabetes mellitus. In eight, plasma renin activity was low; plasma aldosterone concentration was decreased in all; seven had a history of spontaneous hyperkalemia. After administration of glucose orally, there were paradoxical increases in serum potassium levels in seven patients. After potassium loading, maximal values and increments of serum potassium were higher and fractional potassium excretion was lower in the diabetic than in the control subjects, although the differences were not statistically significant. Abnormalities of potassium homeostasis in diabetes are probably related to insulin and mineralocorticoid deficiency. Diabetic patients with hypoaldosteronism have the potential for severe hyperkalemia should renal or extrarenal mechanisms for potassium homeostasis be challenged by severe acidosis be challenged by severe acidosis, diminished renal function, marked hyperglycemia, or administration of potassium salts or potassium-sparing diuretics.

Cerebral salt wasting in a man with carcinomatous meningitis.

The purpose of this report is to alert the clinician that hyponatremic patients with CNS disease do not necessarily have a syndrome of inappropriate secretion of antidiuretic hormone. We describe a patient with hyponatremia and carcinomatous meningitis whose volume contraction resulted from striking urinary sodium losses. Although no longer even alluded to in reviews of hyponatremia, cerebral salt wasting appears to be a real clinical entity that warrants further investigation.

Hyporeninemia and hypoaldosteronism in diabetes mellitus.

The changes in plasma renin activity (PRA) and plasma aldosterone concentration (PA) in response to postural stimuli were evaluated in 12 patients with stable diabetes mellitus and in five volunteers. Seven diabetic patients had hyperkalemia, and several had renal insufficiency and neurological complications. Five diabetics and had normal serum potassium concentration, a mean creatinine clearance within the normal range, and few complications. PRA and PA were measured in these patients and in the control subjects, all of whom were receiving a diet containing 10 mEq of sodium and 50 mEq of potassium while they were in a supine position, after they were tilted to a 90 degrees position, and after upright posture for two hours. The results indicate that impaired responsiveness of PRA and PA may occur in patients with complicated and those with uncomplicated diabetes and may be responsible in part for a relatively high prevalence of hyperkalemia especially in those diabetic patients with reduced renal function.

Can beta-hydroxybutyrate be detected at the bedside by in vitro oxidation with hydrogen peroxide.

The diagnosis of ketoacidosis with an inordinately high plasma and urinary concentration ratio of beta-hydroxybutyrate (beta-OHB) to acetoacetate (AcAc) is difficult, because only AcAc and acetone react with the diagnostic reagents used clinically to detect ketones. The purpose of this study was to assess the validity of the claim that beta-OHB can be identified with a simple modification of the usual bedside test for ketones, using hydrogen peroxide (H2O2) and Ketostix (Ames Division, Miles Laboratories, Inc., Elkhart, Indiana). Unfortunately, the lowest detectable concentration of urinary beta-OHB was 50 mmol/L, and serum beta-OHB could not be detected at levels less than 100 mmol/L, a clinically irrelevant level. The relative insensitivity, the inapplicability to serum, and the potential hazard of the routine use of 30% H2O2 by practicing physicians or houseofficers render the method of limited value.

Decreased quinidine plasma protein binding during hemodialysis.

Quinidine binding to serum proteins was quantitated in 10 regularly dialyzed patients with end-stage renal disease, both under baseline conditions and after heparin during a single hemodialysis. Quinidine binding was determined in vitro, after the addition of 2 micrograms/ml quinidine sulfate, by ultrafiltration combined with spectrophotofluorometry. The baseline percent unbound quinidine concentration in our patients was 6.5 +/- 2.3% (mean +/- SD), a value lower than in normal subjects (9.9 +/- 3.0%, n = 18, p less than 0.005). Binding correlated with both serum albumin (r = 0.72, p less than 0.02) and free fatty acid (r = 0.65, p less than 0.05) concentrations. After heparin there was a rise in percent unbound quinidine (12.2 +/- 5.6%, p less than 0.025) and in free fatty acid concentration (1111 +/- 1202 microEq/l, p = 0.004) in each subject. After heparin the relationship between quinidine binding and free fatty acid concentration was again evident (r = 0.97, p less than 0.001). Dynamic changes in the levels of free quinidine, as well as other drugs during hemodialysis, may require adjustments to avoid toxicity and adverse interactions.

Effect of long-term lithium administration on renal phosphorus handling.

Renal phosphorus handling was evaluated in 12 lithium carbonate-treated psychiatric patients. Serum phosphorus was normal and serum lithium values were within the therapeutic range in all subjects. Serum calcium concentrations measured in 6 of the patients were found to be within the normal range; in the same patients serum parathyroid hormone levels were normal in 4 and slightly elevated in 2. Phosphorus clearance (14 +/- 3 [se] ml/min) and tubular reabsorption of phosphorus (88 +/- 2%) during oral sodium bicarbonate loading were not significantly different from those in 10 healthy control subjects. In a subgroup of 5 patients and 5 control subjects, phosphorus excretion did not increase after bicarbonate loading. In these subjects, phosphorus excretion rates after bicarbonate loading were not different. Although experimental studies suggest that lithium inhibits renal cortical adenylate cyclase stimulation by parathyroid hormone, our data did not indicate any striking effect of long-term lithium administration on serum calcium and serum phosphorus or on renal phosphorus handling.

Serum levels of high-density lipoprotein phospholipids correlate inversely with severity of angiographically defined coronary artery disease.

In an attempt to assess the relationship between lipid abnormalities and severity of coronary artery disease, we measured serum levels of cholesterol (SC), triglycerides (TG), phospholipids (SP), low density lipoprotein cholesterol (LDL-C), very low density lipoprotein cholesterol (VLDL-C), high density lipoprotein cholesterol (HDL-C), and high density lipoprotein phospholipids (HDL-P), in 217 men undergoing diagnostic coronary arteriography. We found significantly higher mean values of HDL-P and HDL-C in men with normal coronaries, but no significant differences in the other measured lipids. While there was no significant difference in HDL-C among patients with one, two or three-vessel disease, there was a negative correlation between HDL-P levels and the severity of the disease. These observations suggest that prospective studies would be of merit to establish the relevance of HDL-P in the development of coronary artery disease.

Interaction of cyclosporine A and nonsteroidal anti-inflammatory drugs on renal function in patients with rheumatoid arthritis.

PURPOSE: To determine the additive renal effects of nonsteroidal anti-inflammatory drugs (NSAIDs) and cyclosporine A (CYA) in patients with rheumatoid arthritis (RA) and to determine the effects of CYA on active RA. PATIENTS AND METHODS: Eleven patients with RA refractory to other agents were treated separately for 2-week periods with an NSAID (sulindac or naproxen), CYA (5 mg/kg/d), and NSAID plus CYA in combination (NSAID/CYA). The NSAID/CYA combination was continued for an additional 20 weeks. Clinical parameters of RA, electrolytes, renal function, and the renin-aldosterone system were evaluated at each interval to determine the potential interaction of these two agents. RESULTS: Combined therapy was effective in suppressing many measures of active RA in 9 of the 11 patients. Adverse drug reactions were common, but withdrawals were limited to hirsutism (one) and peripheral neuropathy (one). In about half of the patients, CYA or NSAID resulted in a decrease in the glomerular filtration rate (GFR) and effective renal plasma flow (ERPF), with a mild reduction in the filtration fraction. With NSAID or CYA, early morning renin-aldosterone system values were mildly suppressed, and their response to ambulation/intravenous (IV) furosemide was not blunted. When combined, NSAID/CYA caused more marked reductions of GFR and ERPF at 2 weeks, and this persisted at 20 weeks. The morning renin-aldosterone system values during administration of NSAID/CYA were suppressed, with an added blunted response to ambulation/IV furosemide. CONCLUSION: As previously suspected, the impairment of renal function when CYA and NSAID are combined is greater than that obtained with either agent alone. This hemodynamic effect was reversible and appeared to be, at least in part, due to renal vasoconstriction.

Impairment of beta 2-adrenoceptor-stimulated potassium uptake in end-stage renal disease.

An abnormality of extrarenal mechanisms is believed to contribute importantly to the impaired potassium homeostasis in chronic renal failure. We evaluated the plasma potassium response to inhalation of albuterol, a beta 2 agonist, in eight patients who had end-stage renal disease and who were undergoing chronic hemodialysis and in eight control subjects. The purpose was to assess if an abnormality of the beta 2 adrenoceptor mechanism is present in uremia. The maximal decrement in plasma potassium concentration in the patients (0.12 +/- 0.04 mEq/L) was significantly less than that of the control subjects (0.30 +/- 0.05). Furthermore, the final plasma potassium concentration slightly exceeded baseline in the patients but was significantly reduced in controls, leading to the conclusion that an abnormal responsiveness of the beta 2 adrenoceptor may contribute to the impaired potassium tolerance found in patients who have end-stage renal disease.

Effect of indomethacin on acute potassium tolerance.

Nonsteroidal anti-inflammatory drugs are believed to impair potassium tolerance in both humans and experimental animals. We evaluated plasma potassium response to an acute potassium chloride load (75 microEq/100 gm body wt) in rats pretreated with indomethacin (10 mg/kg body wt). The increment in plasma potassium concentration in the indomethacin-treated group was significantly higher than that in the control group. In a subset of anuric animals treated with indomethacin, the change in plasma potassium concentration after potassium chloride infusion was similar to that in controls. We conclude that indomethacin disrupts acute potassium tolerance. The abnormality may be related to renal rather than extrarenal mechanisms.

Exacerbation of hepatic encephalopathy by chronic renal failure: response to maintenance hemodialysis.

The consequences of chronic renal insufficiency relevant to hepatic failure are not well appreciated. We describe a patient with chronic cirrhosis and marked porto-systemic shunting who, after the onset of chronic renal failure, developed intractable encephalopathy which improved markedly during an eight month period of maintenance hemodialysis.

Renal acidification in hypothyroid man.

The role of thyroid hormone in renal hydrogen ion secretion remains largely unknown, and there is only limited information on renal acidification in hypothyroid patients. In the present study two of five adult male patients with untreated primary hypothyroidism and without clinical evidence of systemic autoimmune disease were unable to lower their urine pH appropriately after short duration acid-loading. Since, prior to acid-loading, their arterial blood gas values were within the normal range and urinary bicarbonate excretion was trival, the findings are consistent with the incomplete syndrome of distal renal tubular acidosis. Although the mechanism of this abnormality remains unknown, thyroxine deficiency per se may in part be responsible.

Severe cerebral edema in a patient with anasarca and hypernatremia.

We describe a woman whose fatal post-liver transplantation cerebral edema was unexpected and of unusual pathogenesis. Her severe cerebral edema is of considerable pathophysiologic interest: 1) it developed in the setting of marked anasarca and persistent hypernatremia, and 2) although hepatic function was poor, it was not considered sufficiently deranged to induce cerebral edema. Furthermore, there was no histologic evidence of hepatic rejection or antemortem hepatic necrosis. We postulate that an impairment of the blood brain barrier in association with a degree of hepatic dysfunction insufficient by itself to cause cerebral edema permitted the brain interstitial fluid volume to increase pari passu with ECF expansion. Cytotoxic cerebral edema and vascular engorgement may also have contributed to a life-threatening increase in intracranial pressure.

Lipid and lipoprotein levels in undialyzed patients with chronic renal failure.

Lipid and lipoprotein levels were measured in undialyzed uremic men and compared with levels of healthy control subjects. The patients had lower high-density lipoprotein (HDL) cholesterol (mean +/- SD, 46.3 +/- 14.8 vs 54.1 +/- 18.2 mg/dl) and increased serum triglycerides (197 +/- 151 vs 142 +/- 87.7 mg/dl). When compared with patients maintained on dialysis, the undialyzed patients had higher HDL cholesterol (46.3 +/- 14.8 vs 30.3 +/- 13.3 mg/dl), serum cholesterol (226 +/- 81 vs 151 +/- 42 mg/dl), and triglycerides (197 +/- 151 vs 146 +/- 105 mg/dl). The low-density lipoprotein (LDL): high-density lipoprotein cholesterol ratios were 3.78, 3.24, and 2.84 in the dialyzed, undialyzed, and control groups, respectively. Lecithin: cholesterol acyl transferase activity of undialyzed patients was similar to controls when measured by an endogenous substrate assay (148 +/- 112 vs 112 +/- 28 nmol/ml/hr), but were significantly lower when assayed using exogenous substrate (73.3 +/- 25.6 vs 112.8 +/- 7 nmol/ml/hr). The rate of cholesterol transfer (RCT) from HDL to very low density lipoprotein and LDL was in the following order: dialyzed patients (1.85 +/- 1.29 mg/dl/hr) less than undialyzed patients (2.41 +/- 1.57 mg/dl/hr) less than control subjects (4.83 +/- 3.13 mg/dl/hr). Within the undialyzed patient group, black patients had lower serum cholesterol and triglycerides and higher HDL and HDL3 cholesterol than white patients. Apoprotein A-I levels were higher and apoprotein B levels were lower in the black patients. There was a strong correlation (r = 0.9501) between apoprotein A-I and HDL levels in the black patients, but not in the white patients (r = -0.148).(ABSTRACT TRUNCATED AT 250 WORDS)

Blunted kaliuresis after an acute oral potassium load in diabetes mellitus.

It is unknown whether diabetic patients without renal failure or aldosterone deficiency respond normally to potassium administration. Acute oral potassium-loading was carried out in eight diabetic patients with modestly reduced creatinine clearance (Ccr) and in 11 diabetic patients and 13 controls with normal clearances. Only one diabetic patient manifested an inappropriately low upright plasma aldosterone level (6 ng/dL). The percentage of potassium excreted in 4 hour by both groups of diabetic patients was significantly less than that of the controls (decreased Ccr:21% +/- 6%, normal Ccr:36% +/- 5%, controls:54% +/- 5%; p less than 0.01 and 0.05 respectively). On the other hand, the estimated amount of potassium translocated intracellularly tended to be greater in the diabetic patients (18 +/- 3 mmol; 11 +/- 3 mmol) than controls(7 +/- 2 mmol; p less than 0.005 and 0.1 respectively), and the ratio of the increase in plasma (K) to the amount of potassium retained, was lower in diabetic patients, probably indicating enhanced intracellular potassium translocation. The authors conclude that diabetic patients with normal or only slightly reduced renal function (and no aldosterone deficiency) may have a reduced capacity to excrete an acute potassium load but an enhanced capacity to transfer potassium intracellularly.

Disordered breathing patterns during bicarbonate hemodialysis in COPD. Effect of cuprophane versus polysulfone membranes.

This study explored the breathing patterns and arterial blood gases before and during cuprophane (CU) bicarbonate and polysulfone (PS) bicarbonate dialysis in six chronic dialysis patients with mild chronic obstructive pulmonary disease (COPD). The studies were performed in random order during two consecutive dialyses. Breathing patterns were monitored by respiratory impedance plethysmography. Apneic episodes, defined as a decrease in tidal volume of 75% lasting 10 sec, were present before and during hemodialysis. In these patients with COPD a high number of apneic episodes (17 +/- 6 [SE]) were observed during CU bicarbonate hemodialysis. Most of these episodes were central rather than obstructive in character. There were fewer events when the same patients were dialyzed with PS membranes (10 +/- 5; p = 0.05). The decrement in PO2 (baseline to 60 min) was 17 +/- 7 during CU and 4 +/- 5 mmHg during PS dialysis (p = 0.10). Minute ventilation decreased in four of six patients on CU bicarbonate and increased in all six patients on PS bicarbonate. It was concluded that bicarbonate hemodialysis does not completely prevent hypoxemia or apnea during dialysis in patients with COPD. Apneic episodes and hypoxemia appear to be less severe during PS bicarbonate than during CU bicarbonate hemodialysis.

Factors that influence serum hyaluronan levels in hemodialysis patients.

Serum hyaluronan levels are increased in dialysis patients. We evaluated several factors that influence serum hyaluronan levels in 184 patients on chronic hemodialysis (duration 2.3 +/- 2.3 [SD] years). The levels were higher than normal in the whole group and in a subgroup of 133 patients without chronic infection, liver disease, or rheumatoid arthritis (215 +/- 19 and 205 +/- 22 microg/L, respectively). There was a tendency for the levels to be higher in a subgroup of patients with hepatitis c virus (HCV) infection. There was no correlation between hyaluronan levels, alanine aminotransferase (ALT), and duration or dose of dialysis. A weak but highly significant negative correlation between serum albumin levels and serum hyaluronan and ferritin levels was seen. The data suggest that chronic inflammation may explain, at least in part, the increased hyaluronan levels found in chronic dialysis patients.