Increased renal production of transforming growth factor-beta1 in patients with type II diabetes.

Diabetic nephropathy is a common complication in patients with either type I or type II diabetes. The pathogenesis of diabetic nephropathy is thought to involve both metabolic and vascular factors leading to chronic accumulation of glomerular mesangial matrix. In this context, both transforming growth factor-beta (TGF-beta) and endothelin may contribute to these processes. To determine if diabetic patients demonstrate increased renal production of TGF-beta and endothelin, aortic, renal vein, and urinary levels of these factors were measured in 14 type II diabetic patients and 11 nondiabetic patients who were undergoing elective cardiac catheterization. Renal blood flow was measured in all patients to calculate net mass balance across the kidney. Diabetic patients demonstrated net renal production of immunoreactive TGF-beta1 (830 +/- 429 ng/min [mean +/- SE]), whereas nondiabetic patients demonstrated net renal extraction of circulating TGF-beta1 (-3479 +/- 1010 ng/min, P < 0.001). Urinary levels of bioassayable TGF-beta were also significantly increased in diabetic patients compared with nondiabetic patients (2.435 +/- 0.385 vs. 0.569 +/- 0.190 ng/mg creatinine, respectively; P < 0.001). Renal production of immunoreactive endothelin was not significantly increased in diabetic patients. In summary, type II diabetes is associated with enhanced net renal production of TGF-beta1, whereas nondiabetic patients exhibit net renal extraction of circulating TGF-beta1. Increased renal TGF-beta production may be an important manifestation of diabetic kidney disease.

Cause of acute tubular necrosis affects its prognosis. The Auriculin Anaritide Acute Renal Failure Study Group.

BACKGROUND: Acute tubular necrosis (ATN) is the most common type of acute renal failure in hospitalized patients and is associated with a high morbidity and mortality. The cause of ATN can be divided into nephrotoxic, ischemic, or mixed. OBJECTIVE: To test the hypothesis that the cause of ATN affects its clinical outcome. METHODS: The study compares clinical outcomes of patients enrolled in the placebo arm of a multicenter, randomized, double-blinded, placebo-controlled trial of anaritide (Auriculin, synthetic atrial natriuretic peptide, Scios, Mountain View, Calif) in patients with well-defined ATN. Patients were divided prospectively into groups according to the cause of ATN: pure nephrotoxic, pure ischemic, or mixed nephrotoxic and ischemic. Outcomes of interest were dialysis-free survival and all-cause mortality on day 14 and day 21. The causal groups were compared with respect to the prevalence of several comorbidities suspected of affecting the clinical outcomes. RESULTS: Mortality was 10% in the nephrotoxic group and 30% in the ischemic group on day 21. Dialysis-free survival was 66% in the nephrotoxic group and 41% in the ischemic group on day 21. Outcomes in the mixed and ischemic groups were similar. Compared with the nephrotoxic group, there was a significantly higher prevalence of cardiogenic shock, hypotension, sepsis, and respiratory failure and a tendency toward a higher prevalence of acute hepatic dysfunction in the ischemic group. Diabetes mellitus was more prevalent in the nephrotoxic group. Among patients with ischemic ATN, dialysis-free survival improved significantly and mortality tended to decline with advancing age. CONCLUSIONS: Among patients with ATN, those in whom renal ischemia was causative had significantly higher mortality and lower dialysis-free survival than those whose ATN was purely nephrotoxic in origin. This difference in clinical outcomes was associated with a higher prevalence of serious commorbidities in the ischemic ATN group. Advancing age was associated with improved dialysis-free survival and a tendency toward reduced mortality in patients with ischemic ATN.

Pseudohyponatremia: a reappraisal.

Pseudohyponatremia is a falsely low serum sodium measurement. It occurs in cases of extreme hyperlipidemia or hyperproteinemia when serum sodium is measured by some--but not all--laboratory methods. This article reviews the most common techniques for measuring serum sodium levels, explains why pseudohyponatremia occurs, and identifies specific situations in which pseudohyponatremia can lead to dangerous errors in patient management. The review describes the dramatic change in prevalence of the different laboratory methods for measuring serum sodium over the past decade, and emphasizes the need for clinicians to be familiar with the methods of their clinical laboratory in order to properly interpret a reported serum sodium determination. I offer recommendations for the rational use of the different laboratory methods in various clinical situations.

Acute tubular necrosis in patients with diabetes mellitus.

We compared the clinical outcomes of patients with (n = 71) and without (n = 185) diabetes mellitus enrolled into the placebo arm of a large, multicenter clinical trial of patients with acute tubular necrosis (ATN). Compared with the nondiabetic patients, diabetic patients were older (65.5 +/- 12.9 versus 60.7 +/- 18.0 years, P < 0. 05), had higher usual serum creatinine concentration (1.7 +/- 0.6 versus 1.4 +/- 0.5 mg/dL, P < 0.001), and had a higher prevalence of underlying hypertension, coronary artery disease, and congestive heart failure (all P < 0.007). By day 21 after enrollment, neither mortality nor dialysis-free survival was different between the groups. Length of stay for surviving patients, in both the intensive care unit and the hospital, were significantly shorter for the diabetics. Among acute comorbidities predicting mortality or the need for dialysis, sepsis was more prevalent among the nondiabetic patients (18% versus 35%, diabetics versus nondiabetics, P < 0.05). In conclusion, clinical outcomes for diabetic patients with ATN were no worse than for nondiabetic patients, despite their older age and worse underlying renal function. Patients with diabetes mellitus had more chronic cardiovascular disease but were less acutely ill. We speculate that cardiovascular disease is a risk factor for ATN in patients with diabetes mellitus. These results fail to implicate the increasing prevalence of diabetes mellitus in the persistently poor prognosis of patients with ATN.

Prospective study of atrial natriuretic peptide for the prevention of radiocontrast-induced nephropathy.

Radiocontrast-induced nephropathy (RCIN) is a common cause of hospital-acquired acute renal failure and is associated with a high mortality rate. RCIN is potentially preventable, because administration of the radiocontrast agent is predictable, and a high-risk population has been identified. This multicenter, prospective, randomized, double-blind, placebo-controlled trial was performed to evaluate the efficacy of intravenous atrial natriuretic peptide (anaritide, ANP 4-28) to prevent RCIN. Patients with stable chronic renal failure (serum creatinine greater than 1.8 mg/dL or serum creatinine between 1.5 and 1.8 mg/dL with estimated creatinine clearance of < or = 65 mL/min) were assigned to receive either placebo or one of three doses of anaritide (0.01 microg/kg/min, 0.05 microg/kg/min, or 0.1 microg/kg/min) for 30 minutes before and continuing for 30 minutes after radiocontrast administration. All patients were given intravenous 0.45% saline for 12 hours before the radiocontrast procedure and continuing for 12 hours after the last dose of radiocontrast. Both ionic and nonionic radiocontrast agents were administered. RCIN was defined as either an absolute increase of serum creatinine of > or = 0.5 mg/dL or a percent increase of > or = 25% over baseline. Of the 247 patients who completed the study, 50% had diabetes mellitus. There were no statistical differences in baseline serum creatinine, change in serum creatinine, or the incidence of RCIN. The incidence of RCIN was placebo, 19%; anaritide (0.01), 23%; anaritide (0.05), 23%; anaritide (0.1), 25%. Patients with diabetes mellitus had a significantly greater incidence of RCIN: placebo, 26% versus 9%; anaritide (0.01), 33% versus 13%; anaritide (0.05), 26% versus 21%; anaritide (0.1), 39% versus 8% (diabetic v nondiabetic, P < 0.002). There was no effect in the diabetic or nondiabetic groups by anaritide on the incidence of RCIN. Comparison of the highest-risk group of patients, defined as patients with diabetes mellitus and a baseline serum creatinine > or = 1.8 mg/dL, with the lowest-risk group, defined as patients without diabetes mellitus and a baseline serum creatinine of 1.8 mg/dL or less, did not show a beneficial effect of anaritide administration. In conclusion, administration of intravenous anaritide before and during a radiocontrast study did not reduce the incidence of RCIN in patients with preexisting chronic renal failure, with or without diabetes mellitus.

Atrial natriuretic factor in oliguric acute renal failure. Anaritide Acute Renal Failure Study Group.

Atrial natriuretic peptide (ANP), an endogenous hormone synthesized by the cardiac atria, has been shown to improve renal function in multiple animal models of acute renal failure. In a recent multicenter clinical trial of 504 patients with acute tubular necrosis (oliguric and nonoliguric), ANP decreased the need for dialysis only in the oliguric patients. In the present study, 222 patients with oliguric acute renal failure were enrolled into a multicenter, randomized, double-blind, placebo-controlled trial designed to assess prospectively the safety and efficacy of ANP compared with placebo. Subjects were randomized to treatment with a 24-hour infusion of ANP (anaritide, 0.2 microgram/kg/min; synthetic form of human ANP) or placebo. Dialysis and mortality status were followed up for 60 days. The primary efficacy end point was dialysis-free survival through day 21. Dialysis-free survival rates were 21% in the ANP group and 15% in the placebo group (P = 0.22). By day 14 of the study, 64% and 77% of the ANP and placebo groups had undergone dialysis, respectively (P = 0.054), and 9 additional patients (7 patients, ANP group; 2 patients, placebo group) needed dialysis but did not receive it. Although a trend was present, there was no statistically significant beneficial effect of ANP in dialysis-free survival or reduction in dialysis in these subjects with oliguric acute renal failure. Mortality rates through day 60 were 60% versus 56% in the ANP and placebo groups, respectively (P = 0.541). One hundred two of 108 (95%) versus 63 of 114 (55%) patients in the ANP and placebo groups had systolic blood pressures less than 90 mm Hg during the study-drug infusion (P < 0.001). The maximal absolute decrease in systolic blood pressure was significantly greater in the anaritide group than placebo group (33.6 versus 23.9 mm Hg; P < 0.001). This well-characterized population with oliguric acute renal failure had an overall high morbidity and mortality.

Etiology of third-trimester maternal hyperuricemia in nonpreeclamptic twin gestations.

OBJECTIVE: To determine whether the higher maternal serum uric acid levels observed in the third trimester of nonpreeclamptic twin gestations result from increased uric acid production or decreased renal excretion. METHODS: Thirty-four nonpreeclamptic subjects with twin gestations were analyzed, along with 34 singleton controls matched for age, ethnicity, prepregnancy weight, height, and gestational age. For each subject, a serum sample and 24-hour urine specimen were obtained in the third trimester. Serum and urine uric acid and creatinine levels were determined, as well as total 24-hour urine uric acid, uric acid clearance, creatinine clearance, fractional uric acid clearance, and net tubular uric acid absorption. RESULTS: The twin gestation group had significantly higher maternal serum uric acid levels (5.2 +/- 1.2 compared with 4.0 +/- 1.0 mg/dL, P <.001) and maternal serum creatinine levels (0.7 +/- 0.2 compared with 0.5 +/- 0.1 mg/dL, P <.001) than the paired singleton group. This was associated with greater 24-hour urine uric acid excretion (688.7 +/- 167.0 compared with 597.7 +/- 164.2 mg, P =.04) and 24-hour urine creatinine excretion (1268.4 +/- 249.9 compared with 1161.2 +/- 277.1 mg, P =.03) in the twin group. No differences were seen between the groups in uric acid clearance, creatinine clearance, fractional uric acid clearance, filtered uric acid load, or net uric acid absorption. CONCLUSION: The higher maternal serum uric acid levels observed in the third trimester of nonpreeclamptic twin gestations result in part from increased uric acid production, as reflected in the increased daily uric acid excretion.

Pulmonary edema after transfusion in a patient with end-stage renal disease.

AIMS: To describe a patient with end-stage renal disease who developed non-cardiogenic pulmonary edema after transfusion of packed red blood cells. DESIGN: Case report and literature review. RESULTS: The patient under consideration is a 60-year-old woman who developed acute pulmonary edema after transfusion of packed red blood cells without concomitant dialysis. The initial diagnosis of fluid overload was managed by isolated ultrafiltration. Minimal fluid removal led to significant hypotension that was resistant to vasopressors. Subsequent pulmonary artery catheter readings were consistent with non-cardiogenic pulmonary edema. The patient improved spontaneously over the next few days with supportive care only. Plasma from the donors was checked for granulocyte antibodies and antibodies to HLA class I antigens. No granulocyte antibodies were detected in donor plasma but of one the HLA antibodies detected in donor plasma had specificity for a recipient HLA-A antigen. These characteristics supported a final diagnosis of transfusion-related acute lung injury (TRALI). CONCLUSIONS: Acute pulmonary edema following blood transfusion in a dialysis-dependent patient does not always signify fluid overload and nephrologists should be aware of the alternative diagnosis of TRALI. Proper awareness of TRALI will lead to prompt diagnosis and appropriate management.

Disorders of potassium homeostasis in critically ill patients.

Disorders of potassium homeostasis can be life-threatening. This is especially true in critically-ill patients, in whom concurrent disorders may exacerbate the adverse effects of both hyper- and hypokalemia. Alterations in potassium balance are usually multifunctional in origin. Four broad categories encompass the most common diseases and syndromes seen in the intensive care setting: pharmacologic agents, acid-base disturbances, hypomagnesemia, and renal insufficiency. The various influences that disturb the serum potassium concentration may either potentiate or counter-balance one another. The most important clinical manifestations of disorders of potassium homeostasis are those involving the heart: both hyper- and hypokalemia can be associated with lethal arrhythmias. Neuromuscular, renal and metabolic effects are also seen. Severe hyper- and hypokalemia, irrespective of cause, should be treated as medical emergencies.

Schistosoma mansoni: morphologic changes induced by maintenance in vitro.

Adults of Schistosoma mansoni were incubated in several culture media at various time intervals ranging from 2 to 96 hr. The morphologic changes induced by the incubation were documented using both scanning and transmission electron microscopy. These included changes in the tegument, esophageal cells, and cecum. Variability was noted among worms within experimental groups and the surface changes on single worms were frequently observed to have patchy distribution. Based on morphologic changes observed, culture media were ranked as adequate, mediocre, or inadequate. RPMI-1640 + 50% fetal calf serum, Eagle's MEM with Earle's salts (no serum), and McCoy's 5A Medium + serum were judged adequate. Basal Eagle's Medium, Triple Eagle Medium, NCTC-135, and Earle's Balanced Salt Solution (all with or without serum) were judged mediocre. Hanks' Basal Salt Solution (with or without serum) was judged as severely inadequate. All media tested gave better results in the presence of serum. These factors point to the necessity for the use of carefully selected culture media, as well as adequate controls and sampling techniques in the interpretation of in vitro experiments with S. mansoni.

Schistosoma mansoni: evaluation of selected preparative procedures for transmission and scanning electron microscopy.

Evaluation of numerous procedures for collection and preparation of Schistosoma mansoni for scanning (SEM) and transmission microscopy (TEM) revealed that some commonly used methods result in introduction of osmotic or mechanical damage. Modification and selection of appropriate procedures allowed elimination of these artifacts. Not eliminated by these procedures, however, were several kinds of spheres and blebs that were either external to the apical plasma membrane of the tegument or budding from it. After careful examination of all procedures, we concluded that these spheres appear to some extent on all schistosomes prepared for either SEM or TEM and may represent either a normal component of the schistosome surface, a constant host contaminant, or an artifact not eliminated by any of the multiple modifications of technique examined.

Hyperkalemia in dialysis patients.

Serious hyperkalemia is common in patients with end-stage renal disease (ESRD) and accounts for considerable morbidity and death. Mechanisms of extrarenal disposal of potassium (gastrointestinal excretion and cellular uptake) play a crucial role in the defense against hyperkalemia in this population. In this article we review extrarenal potassium homeostasis and its alteration in patients with ESRD. We pay particular attention to the factors that influence the movement of potassium across cell membranes. With that background we discuss the emergency treatment of hyperkalemia in patients with ESRD. We conclude with a review of strategies to reduce the risk of hyperkalemia in this population of patients.

Renal and systemic oxygen consumption in patients with normal and abnormal renal function.

Systemic and renal oxygen consumption and hemodynamics were studied in patients with normal renal function (NI; serum creatinine concentration (Screat), 1.0 +/- 0.04 mg/dL) and those with moderate chronic renal failure with diabetes mellitus Screat, 2.7 +/- 0.2 mg/dL) or without diabetes mellitus (Screat, 2.4 +/- 0.1 mg/dL). Patients with chronic renal failure were anemic and had normal systemic oxygen consumption (NI, 10,564 +/- 277; chronic renal failure, 9,669 +/- 362 mumol of O2/min) and elevated systemic oxygen extraction (NI, 22.9 +/- 1; chronic renal failure, 30.9 +/- 1.2%) (P less than 0.02). Cardiac output and index and arterial oxygen saturation were equivalent in normal patients and in patients with chronic renal failure. Patients with chronic renal failure had higher renal oxygen extraction (NI, 7.3 +/- 0.8; chronic renal failure, 13.9 +/- 1%), lower RBF (NI, 572 +/- 146; chronic renal failure, 197 +/- 20 mL/min/kidney), and lower renal oxygen consumption per kidney (NI, 391 +/- 101; chronic renal failure, 177 +/- 20 mumol of O2/min/kidney) than did normal patients (P less than 0.02). There was a linear relationship between hemoglobin and RBF (r = 0.47, P less than 0.02). Patients with chronic renal failure and diabetes had lower RBF (diabetes mellitus, 146 +/- 23; without diabetes, 242 +/- 28 mL/min/kidney) and renal oxygen consumption per kidney (diabetes mellitus, 131 +/- 21; without diabetes, 218 +/- 29 mumol of O2/min/kidney (P less than 0.03) but equivalent renal oxygen extraction when compared with patients without diabetes. Patients with chronic renal failure without diabetes mellitus had higher renal oxygen consumption when expressed per 100 mL of creatinine clearance (diabetes mellitus, 1,016 +/- 150; without diabetes mellitus, 1,453 +/- 175 mumol of O2/min/100 mL of creatinine clearance; P less than 0.03). There was a significant linear relationship (P less than 0.005, r = 0.38) between calculated creatinine clearance and renal oxygen consumption with a y intercept representing basal renal oxygen consumption (115 mumol of O2/min/kidney) and a slope of 2.3 mumol of O2/mL. Patients with moderate chronic renal failure have normal systemic oxygen consumption but reduced RBF and renal oxygen consumption. The latter parameters are even lower in patients with chronic renal failure and diabetes. Renal hypermetabolism is more likely to exist in nondiabetic than diabetic renal disease. Basic human renal physiology and pathophysiology are described by the relationships between renal oxygen consumption, blood flow, oxygen extraction, and creatinine clearance in patients with normal and abnormal renal function of varied cause.

Radiocontrast-induced nephropathy in humans: role of renal vasoconstriction.

Radiocontrast-induced nephropathy (RCIN) is a common cause of acute renal failure in hospitalized patients. Renal vasoconstriction figures prominently in the proposed pathogenesis of RCIN based on animal experiments. Prior human studies examining renal hemodynamic changes after contrast medium (CM) injection are inconclusive. No previous study of animals or humans has established a relationship between CM-associated renal hemodynamic changes and the subsequent development of RCIN. In the present study, we examined the renal hemodynamic effects of CM in patients at high risk of RCIN. In addition, we related those effects to the subsequent development of RCIN. Using renal vein thermodilution catheters, we measured renal blood flow (RBF) in 12 patients with chronic renal failure [serum creatinine (SCr) greater than or equal to 159 mumol/liter] during ionic CM injection for cardiac catheterization. We made measurements at the start of the procedure (t = 0), before the ventriculogram (t = 5), after the ventriculogram (t = 15), and after the coronary angiogram (t = 65). We measured SCr at t = 0 and again 24 and 48 hours later. Mean RBF for the group tended to increase after the ventriculogram, and increased significantly by t = 65 (P less than 0.005 vs. t = 0). When examined by individual patient, RBF fell below baseline in three patients (30%) at t = 15, but rose above baseline again by t = 65. Only one patient (8.3%) had a fall in RBF below baseline at t = 65. RCIN (defined as an increase in SCr greater than or equal to 25% above baseline) developed in six patients (50%) within 48 hours.(ABSTRACT TRUNCATED AT 250 WORDS)

Risk of radiocontrast nephropathy in patients with and without diabetes mellitus.

The present study was designed to test whether altered renovascular reactivity is associated with the increased risk of radio-contrast nephropathy (RCN) in diabetics. We studied 50 patients (24 diabetics, 26 nondiabetics) with chronic renal insufficiency undergoing cardiac catheterization. Patients were randomized to receive either saline, or one of three renal vasodilator/diuretic drugs--dopamine, atrial natriuretic peptide (ANP), or mannitol--by intravenous infusion during cardiac catheterization. Renal blood flow (RBF) was measured by thermodilution at various time points during cardiac catheterization. RCN was defined as an increase in PCr of at least 25% over baseline within 48 hours of cardiac catheterization. Baseline PCr and creatinine clearance were similar in diabetics and nondiabetics (2.6 +/- 0.2 mg/dl vs. 2.4 +/- 0.1 mg/dl, and 32 +/- 3 ml/min vs. 34 +/- 3 ml/min, respectively), but baseline RBF was significantly lower in diabetics (154 +/- 21 ml/min/kidney vs. 277 +/- 36 ml/min/kidney, P < 0.05). Diabetic patients exposed to the three vasodilator/diuretic drugs had the greatest increase in RBF throughout cardiac catheterization. The incidence of RCN among the diabetics receiving those drugs was 83%, 83% and 75%, in the dopamine, ANP and mannitol groups, respectively. In contrast, among the nondiabetics in each of those groups the incidence of RCN was zero (all P < 0.05, diabetics vs. nondiabetics). In the saline control group the rates of RCN in the diabetics and nondiabetics were 43% and 38%, respectively (NS). In conclusion, the increased risk of RCN among diabetics was associated with exaggerated renovascular reactivity: baseline vasoconstriction and enhanced vasodilation with vasodilator/diuretic drugs. These same drugs, however, reduced the risk of RCN in nondiabetic patients.

Dopamine and renal blood flow in radiocontrast-induced nephropathy in humans.

Previous studies suggest a role for renal vasoconstriction in the pathogenesis of radiocontrast-induced nephropathy (RCIN). A renal vasodilator such as dopamine may be protective. However, the effect of dopamine on renal blood flow (RBF) in patients with chronic renal failure (CRF) is controversial. Patients with CRF of diabetic (DM) or nondiabetic (NDM) origin were hydrated with 0.45% NaCl intravenously at 100 mL/h for 12 h and then randomized to either 0.45% NaCl IV at 100 mL/h (Group 1) or dopamine IV at 2 micrograms/kg/min in 0.45% NaCl at 100 mL/h for 2 h during and after cardiac catheterization. Mean arterial pressure (MAP), cardiac output (CO), and RBF were measured at baseline (t = 0), after 5 min of vehicle (Group 1) or dopamine (Group 2) but before ionic radiocontrast (t = 5 min), after ventriculogram (t = 15 min), and after coronary angiography (t = 65 min). Serum creatinine (SCr) was measured at baseline and 24 and 48 h after cardiac catheterization. RCIN was defined as a 25% increase of SCr above baseline 48 h after cardiac catheterization. Baseline characteristics demonstrated the groups to be equivalent in age, SCr, creatinine clearance, CO, MAP, RBF, and radiocontrast dose administered. The incidence of RCIN was not different between Group 1 and Group 2 (Group 1, 6 of 15 patients; Group 2, 5 of 15 patients). Dopamine infusion was associated with a significant increase in RBF at 5 min (Group 1, 110 +/- 13%; Group 2, 193 +/- 40% at t = 5, p < .05). RBF remained elevated throughout the catheterization in Group 2.(ABSTRACT TRUNCATED AT 250 WORDS)

Effects of atrial natriuretic peptide versus mannitol on renal blood flow during radiocontrast infusion in chronic renal failure.

This study was performed to investigate the effects of atrial natriuretic peptide (ANP) and mannitol on renal blood flow (RBF) and radiocontrast-induced nephropathy (RCIN) in human subjects with chronic renal failure. ANP preserves glomerular filtration rate or RBF (or both) in severe animal models of acute renal failure. Radiocontrast is known to substantially decrease RBF and can induce acute renal failure. Twenty consecutive patients with chronic renal failure (60% with diabetes) were randomized in a prospective, double-blind fashion to receive either ANP (50 micrograms bolus, then 1 microgram/min infusion) or mannitol (15% at 100 ml/hr) for 2 hours before and during cardiac catheterization with diatrizoate. Baseline serum creatinine level (ANP 2.4 +/- 0.7 mg/dl, mannitol 2.5 +/- 0.8 mg/dl), medications, and quantity of radiocontrast were similar in both groups. Direct measurements of RBF were made with thermodilution catheters placed in the left renal vein. RBF rose significantly (p less than 0.05), to 198% of baseline at 15 minutes and 166% of baseline at 65 minutes in the group receiving ANP and remained stable in the group receiving mannitol. ANP levels rose significantly from baseline at 5, 15, 65 and 120 minutes in both groups (p less than 0.05). Acute renal failure defined as a 0.5 mg/dl rise of creatinine within 24 hours of cardiac catheterization, developed only in patients with diabetes mellitus and was similar in both experimental groups (ANP, 50%; mannitol, 30%). Only patients with diabetes mellitus responded with an increase in RBF after a 5-minute infusion of either ANP or mannitol (diabetes, 165% +/- 28% baseline; no diabetes, 96% +/- 8% baseline) (p less than 0.05). In conclusion, RBF was maintained or increased despite administration of radiocontrast, a documented renal vasoconstrictor. Patients with diabetes mellitus had a renal vasodilatory response to drug infusion. Acute renal failure occurred to a similar extent in both groups. Plasma ANP levels rose significantly in both groups. Mannitol may induce ANP release, thus contributing to mannitol's renal effects.

Loin pain hematuria syndrome.

LPHS is a disorder of obscure etiology and inconsistent pathology whose most prominent clinical feature is severe flank pain. Were it not for the hematuria which nearly always accompanies the pain, there would be no specific objective correlate of the syndrome. In this sense, it is similar to a number of chronic conditions which have inspired heated controversy about their very existence as discrete diseases. As the foregoing discussion of pathogenesis, pathology and diagnosis illustrates, with respect to two important characteristics of a 'prototypical' disease--specificity and mechanism--LPHS falls far short. This, coupled with a rather unimpressive 'visible' concomitant of the symptoms (hematuria), has inspired skepticism and even suspicion in some physicians confronted with the demands for analgesia by these patients. On the part of physicians who have been involved in the care of these patients over time, however, there is no doubt that they suffer from a bona fide illness, if not a disease. The severity of the illness is evinced by the rather extreme measures that have been taken in its treatment; e.g., surgical denervation of the kidney, nephrectomy, autotransplantation. Only the last of these appears to offer the hope of enduring pain relief while preserving renal function, but the risk of pain recurrence in the autograft may limit the usefulness of this procedure. Accordingly, narcotic analgesics may need to be the treatment of first and last resort. Development of specific treatment will depend upon elucidating the pathogenesis of the disorder. The available data suggest further investigation of the role of vasoactive mediators, and the coagulation and immune systems.

Mannitol stimulates atrial natriuretic peptide release in humans.

The purpose of this study was to determine if mannitol stimulates atrial natriuretic peptide (ANP) release in humans and to examine potential mechanisms for this effect. Twenty patients requiring cardiac catheterization were randomized to receive either mannitol (15-g bolus followed by 15% infusion mixed in 75 mmol/L saline at 100 mL/h for 1 hour) or an equal volume of 75 mmol/L saline, intravenously (IV). All measurements were made at three time points: at baseline, at 10 minutes (after the bolus but before radiocontrast administration), and at 60 minutes (after completion of the study). Baseline plasma ANP (PANP) measurements (mean +/- SE) were similar in both groups (saline, 73 +/- 38 pg/mL; mannitol, 62 +/- 11 pg/mL). PANP increased significantly over time for the set of all patients (analysis of variance [ANOVA], P less than 0.05); however, at 10 minutes PANP increased significantly only in the group receiving mannitol (saline, 76 +/- 43 pg/mL; mannitol, 100 +/- 29 pg/mL) (P less than 0.04). Serum osmolality (SOSM), over time for the set of all patients (ANOVA, P less than 0.04). At 10 minutes there were significant increases only in the group receiving mannitol, and after radiocontrast, there were significant increases in both groups for all parameters. Regression analysis demonstrated a significant correlation between the change in PANP and the change in SOSM (P less than 0.04, r = 0.33). In conclusion, intravascular infusion of mannitol or radiocontrast increased PANP levels. The mechanism may be multifactorial, with a potential role for an increase in SOSM and/or PADH.

Plasma leptin is partly cleared by the kidney and is elevated in hemodialysis patients.

Leptin, the gene product of the ob gene, is important in the control of appetite in rodents and may have an important role in humans. The clearance of leptin from the circulation is unknown. As the leptin receptor is present in the kidney, we evaluated the role of the kidney in removing circulating leptin in humans. We measured leptin in aortic and renal vein plasma in 8 patients with intact renal function and 6 patients with impaired renal function who were undergoing elective cardiac catheterization. Renal blood flow was measured in all patients to calculate net mass balance across the kidney. In patients with intact renal function there is net renal uptake of 12% of circulating leptin, whereas in patients with renal insufficiency there is no renal uptake of leptin. In a separate cohort of 36 patients with end-stage renal failure on hemodialysis, peripheral leptin levels factored for body mass index was increased by > fourfold as compared to a group of healthy controls (N = 338). In addition, plasma leptin is not cleared by hemodialysis with a modified cellulose membrane. Additional studies are required to evaluate the role of leptin in mediating the anorexia of uremia.