Fluid secretion in isolated proximal straight renal tubules. Effect of human uremic serum.

We have examined the effect of normal and uremic human sera on the transtubular flow of fluid in isolated perfused segments of rabbit proximal convoluted and straight renal tubules. Proximal convoluted and straight tubules absorbed fluid from the lumen when the external bath was normal rabbit serum. Normal human sera in the bath depressed net fluid absorption in both tubular segments, but more importantly, uremic human serum caused proximal straight tubules to secrete fluid into the lumen. Fluid secretion was also demonstrated indirectly by observing in nonperfused proximal straight, but not proximal convoluted tubules, that the normally collapsed lumens opened widely in uremic serum. Nonperfused proximal straight tubules developed expanded lumens even after a 25-fold dilution of human uremic serum with normal rabbit serum, whereas lumen expansion occurred only in undiluted normal human serum, on the average. Serum from acutely uremic rabbits possessed secretory activity but normal rabbit serum did not. The secretory effect of uremic sera in proximal straight tubules was inhibited by cooling and ouabain and probenecid. The secretory activity of uremic sera was removed by dialysis, but not by freezing or boiling. Para-aminohippurate and benzoate caused fluid secretion in proximal straight tubules but urea, creatinine, guanidinosuccinate, and urate did not. On the basis of these results, we suggest that the secretory factor in serum may be a substance or group of substances possibly related to the hippurate class of organic molecules that are accumulated to relatively high concentrations in renal failure. The secretory material in the serum of uremic patients may significantly influence the transport of salt and water in relatively intact residual nephrons.

Prognosis for recovery of function in acute renal failure. Value of the renal image obtained using iodohippurate sodium I 131.

Twenty-four survivors of acute, nonobstructive, nonnephritic renal failure had a renal scan using iodohippurate sodium I 131 performed early in the acute illness. Scans were judged according to whether the renal images were prominent, faint, or absent during the first 30 minutes after intravenous injection of 100 to 250 microcuries of iodohippurate sodium I 131. All ten patients with prominent renal images attained life-sustaining renal function with an average postrecovery creatinine clearance of 80 ml/min. Of the seven patients with faint renal images, six recovered life-sustaining renal function (average creatinine clearance of 39 ml/min), and one required chronic hemodialysis. Seven patients had no renal image initially; four recovered life-sustaining renal function with an average creatinine clearance of 25 ml/min; three required chronic hemodialysis. We conclude that, for patients with acute renal failure, the appearance of the renal image obtained using this substance is an important indicator of renal viability and of the likelihood for functional recovery.

Continuous ambulatory peritoneal dialysis for psoriasis. A report of four cases.

Four patients with psoriasis were treated with continuous ambulatory peritoneal dialysis (CAPD). Two were being treated for renal failure; the other two had normal renal function and were being treated exclusively for psoriasis. With CAPD at a rate of three to four exchanges per day, the psoriasis cleared completely in the two patients with renal failure and improved in the other two. In the patients without renal failure, low-flow peritoneal dialysis (one exchange per day) seemed to be of some value in maintaining remission but was ineffective in treating more active disease. Long-term therapy (greater than or equal to 12 weeks) with three or four daily exchanges may be needed for initial complete remission, and continuous treatment may be needed to prevent relapse. Thus, CAPD shows promise for the study of psoriasis and may be a last-resort treatment for severe, disabling cases.

Effect of diet on serum accumulation and renal excretion of aryl acids and secretory activity in normal and uremic man.

The influence of diet on aryl acid metabolism was determined in normal and azotemic subjects. Aryl acid content of serum and urine was estimated by fluorometry in relation to hippuric acid as a standard (FI-Hipp). Secretory activity, a reflection of the biological potency of aromatic acids in serum and urine, was determined by bioassay. The urinary excretion of FI-Hipp and secretory activity of five normal persons on an ad lib diet was 0.78 and 2.25 mM/day, respectively; similar values were observed in two subjects with chronic renal insufficiency. Subjects were fed prunes and cranberries, since these foods contain abundant quantities of hippurate precursors. Prunes 1.5 g/kg body weight, caused the urinary excretion of both FI-Hipp and secretory activity to increase about tenfold in normal and azotemic subjects. Prune feeding caused the serum levels of FI-Hipp and secretory activity to increase about threefold. Cranberries increased the renal excretion of FI-Hipp and secretory activity as did the ingestion of a beverage containing benzoate as a preservative. On the basis of these studies it is clear that diet is an important determinant of the load of aryl acids for urinary excretion; in patients with renal insufficiency the ingestion of foods containing precursors may cause serum level of biologically active aryl acids to increase strikingly.

Severe recurrent alkalemia in a patient undergoing continuous cyclic peritoneal dialysis.

Chronic renal failure is commonly associated with acid-base disorders that are corrected with the institution of maintenance peritoneal dialysis. Severe shifts in systemic pH that occur in patients undergoing peritoneal dialysis are usually acidemic shifts due to inadequate replacement of the kidney's ability to excrete acid and regenerate bicarbonate. This report describes a severe alkalemic shift in pH in a patient undergoing continuous cyclic peritoneal dialysis due to a failure of dialysis to substitute for the kidney's normal response to simple respiratory alkalosis. This case emphasizes that in patients undergoing peritoneal dialysis, physicians must actively provide the "renal compensation" for an acid-base disorder and change the dialysis prescription.

Importance of the autocontrol crossmatch in human renal transplantation.

The killing of donor cells in the standard lymphocyte crossmatch is considered strong evidence for preformed antibodies in the recipients's serum. Moreover, it is generally accepted that presensitization has occurred if any of the stored sera kill the donor cells. In our hands, if either the current or the stored sera kill the donor cells, it precludes transplantation. In nine cases we discovered that the recipient's sera also killed the recipient's own lymphocytes, a positive autocontrol test, indicating that factors other than conventional preformed cytotoxic antibodies were responsible for the positive standard crossmatch. The nine patients who demonstrated a positive standard crossmatch and a positive autocontrol for those sera received cadaver allografts. None of the kidneys were rejected hyperacutely and all are functioning adequately. We conclude that the autocontrol crossmatch is an important adjunct for uncovering false positive reactions in the standard lymphocyte crossmatch test.

Correlation of spontaneous leukocyte blastogenesis with human renal allograft rejection.

Spontaneous blastogenesis of peripheral blood mononuclear cells in recipients of renal allografts was studied by incorporation of 3H-thymidine. Three different levels of reactivity were observed that correlated with the patient's clinical course. Low levels of blast activity (i.e., median 680 dpm/million cells with 95% confidence interval (CI) of 480 to 880 dpm) were observed in pretransplant patients. A moderate elevation (median 3,00 dpm with CI of 2,300 to 5,300 dpm) was noted post-transplantation during quiescent intervals and following the onset of acute reversed rejection. Marked elevations, i.e., values greater than 10,000 dpm frequently were observed within 6 days prior to rejections (median 21,000 with CI of 7,400 to 34,000 dpm) and during sustained rejections (median 14,000 with CI of 8,800 to 19,600 dpm).

Cadaveric kidneys for transplantation. A paradox of shortage in the face of plenty.

The number of cadaveric kidneys currently available for transplantation is insufficient; therefore, the Center for Disease Control (CDC) undertook a collaborative pilot project to increase the number of cadaveric kidneys available for transplantation. In phase one, a retrospective review of medical records of in-hospital deaths was done to determine the potential number of cadaveric kidney donors and to define the characteristics of potential donors. The medical records of 10,420 (43.1%) of the 24,164 patients who died in 67 acute-care hospitals in Georgia, Kansas, and Missouri were retrieved. In addition to determining suitability for donorship, criteria were developed to reflect the broadest range of criteria in use. By center-specific criteria there were 1.7 potential donors/100 in-hospital deaths, which could make available 109 kidneys/million population. By broad intercenter criteria there were 3.5 potential donors/100 in-hospital deaths, which could provide 232 kidneys/million population. During 1975, by center-specific criteria, kidneys from 19.3% of the suitable potential donors were retrieved. The small number of transplantable cadaveric kidneys retrieved was not attributable to lack of suitable organs but rather the failure to identify suitable donors, obtain consent, and retrieve the kidneys.

Remission of nephrotic syndrome in type 1 diabetes: long-term follow-up of patients in the Captopril Study.

In 1994, we reported a 3.4 +/- 0.8 year follow-up of the eight patients who experienced remission of nephrotic syndrome during the Collaborative Study Group-sponsored, multicenter trial of captopril therapy in patients with type 1 diabetes with nephropathy (Captopril Study). Of the 409 patients randomized to treatment on the Captopril Study, 108 had nephrotic syndrome (24-hour proteinuria >/= 3.5 g of protein) at baseline. Of these 108 patients, 8 experienced remission of nephrotic syndrome (proteinuria

Organized kidney retrieval on a regional basis. A new approach.

A network of small to medium-sized communities has been developed to increase the supply of cadaveric kidneys for renal allotransplantation. After a training period, community physicians and the community hospitals were designated as members of the transplant team to retrieve kidneys. A threefold increase in the number of cadaveric kidneys has resulted from this project. This mechanism for organized kidney retrieval on a regional basis could be used to augment the supply of cadaveric organs in other areas of the United States.

Double-blind, placebo-controlled study of ramipril in diabetics with mild to moderate hypertension.

Although hypertension and diabetes mellitus frequently appear as comorbidities, the pharmacotherapy of hypertension in patients with diabetes mellitus can aggravate underlying carbohydrate and lipid abnormalities. To evaluate the efficacy and safety of the long-acting angiotensin converting enzyme inhibitor ramipril in patients with insulin-dependent or non-insulin-dependent diabetes mellitus, the authors conducted a double-blind, placebo-controlled study. After a single-blind washout period, 58 patients were randomly assigned to receive 2.5 mg of ramipril or a 2.5-mg placebo, each once daily. Each patient underwent titration and maintenance phases for a total treatment period of 12 weeks. By the end of maintenance, 54% of patients maintained the target blood pressure 24 hours after receiving ramipril compared with 19% in the placebo group (P = 0.008). Between baseline and the end of maintenance, ramipril decreased mean supine systolic/diastolic blood pressure (SBP/DBP) measured 24 hours after the last dose by 9/8 mmHg (P < or = 0.001/P < or = 0.001); placebo decreased SBP/DBP by 2/4 mmHg (NS/P < or = 0.05). Between-group differences were significant (P < 0.05). During this time, blood glucose, hemoglobin Alc, lipoproteins, and biochemistry were unchanged in the ramipril group. There were no between-group differences in the number or types of adverse events. In our study of patients with diabetes mellitus, once-daily ramipril controlled blood pressure, was well tolerated, and had no effects on carbohydrate or lipid metabolism.

Sex differences in extracellular and intracellular calcium-mediated vascular reactivity to vasopressin in rat aorta.

In rat thoracic aorta, contractile responses to arginine vasopressin are two-fold higher in females than in males. To determine the roles of extracellular and intracellular Ca2+ in this sexual dimorphism in vascular function, vascular reactivity and Ca2+ channel function were examined in thoracic aortae of male and female rats. In the presence of diltiazem (10 microM), maximal contraction to vasopressin was reduced to a greater extent in male (65+/-2%) than in female aortae (38+/-1%). Maximal contractile responses to KCl and Bay K 8644 were similar in male and female aortae. Sensitivity to KCI was slightly but significantly higher in male than in female aorta; in contrast, sensitivity to Bay K 8644 was nearly three-fold higher in males than in females. Removal of the endothelium enhanced sensitivity to KCl similarly in male and female aortae. In the presence of simvastatin (60 microM; an inhibitor of intracellular Ca2+ release), reactivity to vasopressin was reduced substantially in female (42+/-1%) but unaltered in male aortae. Removal of the endothelium enhanced the inhibitory effect of simvastatin in both female (73+/-2%) and male aortae (41+/-2%). These findings demonstrate that male aortae depend more upon extracellular Ca2+ influx, whereas female aortae depend more upon intracellular Ca2+ release for vasopressin-induced contraction.

Using chart reviews to assess residents' performances of components of physical examinations: a pilot study.

PURPOSE: To evaluate chart review as a method of assessing residents' performances of physical examinations in an ambulatory care setting. METHOD: In 1992, nurse authors at the Affiliated Hospitals at Canton of the Northeastern Ohio Universities College of Medicine assessed whether 22 internal medicine residents performed ten components of the physical examination by interviewing patient volunteers immediately after the patients' examinations. A total of 89 patient interviewees were included in the analysis; these patients were all new outpatients who had been scheduled for initial visits to obtain complete histories and physical examinations. Charts for the same patients were then retrospectively reviewed. The residents and faculty were blinded to both the chart reviews and the interviews. Statistical methods used were Pearson correlational analysis and variance-component analysis. RESULTS: The interviews and chart reviews showed 81% agreement in component performance. Completeness of the physical examination (whether measured by chart review or interview) did not correlate with other standard methods of resident evaluation, and completeness did not show a significant association with characteristics of the residents and patients. Two of the 22 residents assessed were identified as having completeness scores so low as to be unsatisfactory. CONCLUSION: That residents were identified as failing to perform examination components suggests that chart reviews, especially when independently verified by patient interviews, may be a useful evaluation tool for identifying inadequate performance of components of the physical examination and may identify the need for remediation.

Postoperative acute pulmonary edema: a rare presentation of pheochromocytoma.

A 39-year-old white female underwent an uneventful vaginal hysterectomy for dysfunctional bleeding. Evaluating a mild aortic insufficiency murmur preoperatively an echocardiogram revealed normal left ventricular wall motion and function. Postoperatively the patient developed severe abdominal pain, acute hypertension (200/100 mmHg), and sinus tachycardia. Within minutes she decompensated into acute pulmonary edema. ECG demonstrated acute ST segment elevation in the precordial leads consistent with acute infarction. Emergency left heart catheterization showed normal coronary vessels with severe left ventricular dysfunction. An abdominal ultrasound was obtained, revealing a right adrenal mass. Plasma epinephrine was 334, norepinephrine 34,543 pg/ml; urine epinephrine 45, urine norepinephrine 2,137 micrograms/24 hours. She was started on prazosin and nifedipine sustained release with good blood pressure control. Four days later, an echocardiogram demonstrated the left ventricular wall motion reverting to normal. The adrenal tumor was subsequently resected successfully. Acute pulmonary edema causing dilated cardiomyopathy is a rare complication of pheochromocytoma that has been seldomly reported. A progressive fatal course is common: reversibility and survival depend on identifying and removing the pheochromocytoma.

Eosinophils in urine revisited.

The finding of eosinophils in the urine has been suggested to be useful in establishing the diagnosis of acute interstitial nephritis (AIN). The diagnostic accuracy of this test has not yet been defined. It is the purpose of this study to define the specificity, sensitivity, and the predictive positive and negative values for the presence of eosinophils in the urine. One hundred forty-eight patients with pyuria were tested for the presence or absence of urinary eosinophils. In this group consecutively admitted to the hospital with WBC in the urine, 4% of patients had urinary eosinophilia of greater than 1 eosinophil per 100 cells. Since none of this group had the diagnosis of AIN, the false positive rate was 4% and the specificity was 96%. In a selected group of patients in which the diagnosis of AIN was suspected by a nephrology consultant, urinary eosinophils were found in 6 of 15 patients with a confirmed diagnosis of AIN but were also found in 10 of 36 patients with another renal diagnosis. The sensitivity for eosinophiluria was 40% and the specificity was 72% with a positive predictive value of only 38%. We conclude that eosinophiluria is not an accurate test for the diagnosis of AIN. The false positive and negative rates are too high to confirm an AIN diagnosis.

Geriatric renal function: estimating glomerular filtration in an ambulatory elderly population.

In elderly individuals, serum creatinine may remain normal as glomerular filtration rate (gfr) declines. Therefore, the estimation of glomerular filtration utilizing mathematical models incorporates age as an important variable. In order to adjust drug dosages and diagnose renal disease earlier in the elderly, a variety of such simplified estimates of gfr have been applied. Unfortunately, no estimator is as accurate as the cumbersome gold standards (e.g. inulin or iothalamate clearance) and the reliability of each may vary with the particular clinical setting. The purpose of this study was to critically evaluate three commonly used estimators of gfr-i.e., creatinine clearance (CC), Cockroft-Gault (CG), and 100 over serum creatinine (100/SC)-comparing them to iothalamate clearance (IC) in a group of healthy ambulatory geriatric subjects (n = 41; ages 65-85). IC declined 1 ml/min per year of age in our sample. CC demonstrated a similar decline, a correlation of 0.83 with IC, and moderate error relative to IC of 17% at the mean (standard error [SE] = 12.3). In contrast, 100/SC correlated only 0.56 with IC, demonstrated a large positive bias (41 ml/min), and showed no age-related decline. An age correction to 100/SC similar to that utilized in the CG formula was clearly necessary. Despite the age and weight correction used in the CG formula, we found the estimates from it to be inaccurate (correlation = 0.5; SE = 23.8). A simpler age-corrected formula (Est. IC = 1/2 [100/SC] + 88-age) was derived and proved significantly superior to CG in our ambulatory geriatric sample, but still exhibited enough error (SE = 16.4) to question its clinical utility. It appears that serum creatinine based estimates of gfr in the elderly may not provide accurate results.

Nephrologists' subjective attitudes towards end-of-life issues and the conduct of terminal care.

Decisions which determine the duration and outcome of terminal care should be influenced by patient autonomy. Studies suggest, however, that end-of-life decision-making is more complex than a single principle and that physicians may be responsible for selected aspects of terminal care independent of patient choice. To study how nephrologists' perceptions toward end-of-life issues may affect decision-making, we anonymously surveyed 125 of them. The study employed the straightforward terminology of "hastening death" rather than adopting the ambiguous term "euthanasia" or the narrow term "assisted suicide." Subjective physician profiles demonstrated that nephrologists who are less comfortable with dying patients were significantly less likely to report that they omitted life-prolonging measures (p = 0.02) and more likely to report that they would not initiate measures in order to hasten death even were it legal (p = 0.04). Ninety-eight percent of nephrologists reported omissions in terminal care with patient knowledge and 80% without patient knowledge. In contrast, forty-three percent of the nephrologists said that were it to become legal to initiate measures in order to hasten death, they would "never" do so. The ethical framework utilized for discontinuation of dialysis decisions incorporated medical benefit (cancer as criterion, 48%; multisystem complications, 84%; dementia 79%) and quality of life criteria. Twenty-five percent of nephrologists admitted difficulty with advance directives if the directives clashed with heir beliefs. ESRD end-of-life decision-making in the USA may be altered by the subjective characteristics of nephrologists. In particular, nephrologists' level of discomfort with patient mortality is linked with their reported management of terminal patients.

Aspergillus discitis with acute disc abscess.

STUDY DESIGN: Aspergillus osteomyelitis of the vertebral body and disc space is rare. This report discusses a case that occurred in an immunosuppressed 29-year-old man and reviews the pertinent medical literature. OBJECTIVES: To review the management and treatment of Aspergillus osteomyelitis of the vertebral body and disc space. SUMMARY OF BACKGROUND DATA: The patient presented with acute neurologic compromise resulting from L5-S1 discitis and a large epidural soft tissue component secondary to the Aspergillus infection. RESULTS: The patient underwent aggressive surgical debridement along with treatment with amphotericin B and had a complete clinical recovery. CONCLUSIONS: The authors recommend a combined medical-surgical approach in most cases of vertebral Aspergillus osteomyelitis. Early surgery with vigorous surgical debridement along with antifungal treatment seems to yield a good outcome.

Acute effects of nifedipine on renal electrolyte excretion in normal and hypertensive subjects.

The role of renal calcium handling in the hypotensive response to calcium channel blockers has not been investigated previously. The acute vasodilatory effect of calcium channel blockers may be accompanied by changes in renal electrolyte handling that are important in renal electrolyte handling that are important in producing the hypotensive response seen with these agents. Nifedipine has been shown to cause acute and chronic natriuresis and diuresis, which are important in the ability to use nifedipine chronically in essential hypertension. We prospectively investigated the acute effect of 10 mg of nifedipine orally on renal cation handling in normotensive and untreated essential hypertensive subjects during a standard oral water load. At baseline there was no difference between normotensives and hypertensives in serum ionized calcium or magnesium, or in the urinary fractional excretion of these two cations. Oral nifedipine acutely increased the fractional excretion of sodium without changing the fractional excretion of calcium or magnesium. Nifedipine did not alter the serum concentrations of sodium, calcium, or magnesium. Augmented sodium excretion may play a role in the acute hypotensive response to oral nifedipine. The acute hypotensive response does not seem to be caused by altered renal handling of calcium or magnesium. Counterbalancing effects of nifedipine on proximal and distal nephron calcium handling may explain the disassociation of augmented sodium excretion and no net change in calcium excretion.

Gold nephropathy. Ultrastructural, fluorescence, and microanalytic studies of two patients.

Renal biopsy specimens from two patients with gold nephropathy showed two distinctly different types of alterations. The first demonstrated lesions suggestive of immunologic injury primarily to the glomerulus and identical with membranous glomerulonephritis. The second had no evidence of immunologic injury, but contained extensive vacuolar degeneration of proximal tubular epithelial cells. Ultrastructurally, the vacuoles contained lipid materials and occupied the basal portion of the cells. Other tubular cells contained numerous "gold-containing" cytosegresomes. In this second specimen, it appeared that the filtered gold had a direct toxic effect on the tubular epithelium and perhaps also on the glomerular capillary wall. These findings suggest that gold nephropathy may indeed be a spectrum of a combination of both direct toxic and immunologic injury to glomeruli and tubules.