Experience with outpatient computed tomographic-guided renal biopsy.

Native kidney biopsy is still performed primarily with hospital inpatient observation period. Experience with outpatient Computed Tomographic (CT)-guided renal biopsy at Yale New Haven Medical Center was studied to assess efficacy and safety. A total of 146 outpatient native kidney biopsies were identified between 1995 and 2001. Records were reviewed for demographics, clinical, and laboratory data and details of the procedure. Time of admission to the outpatient unit, duration of procedure and post-biopsy observation period were recorded. Complications such as bleeding, infection, admission to the hospital, transfusion, or intervention for continued bleeding were noted. Mean age was 43.9 ± 14.9 years and mean serum creatinine was 1.8 ± 1.4 mg/dl. Renal size averaged 11.4 cm. Post-procedure observation time of 4 - 6 h appeared to be adequate. Diagnostic tissue was successfully sampled in 98.6% of cases. Procedure was well tolerated with no hemodynamically significant changes. Hematocrit and hemoglobin concentration changes averaged 3.6 ± 2.5% and 1.0 ± 0.9 mg/dl, respectively (p < 0.001). There were no instances of death or need for intervention. Transfusion was required in 1 patient while 6 patients had detectable bleeding and were hospitalized for observation. Outpatient CT-guided kidney biopsy provides adequate tissue and appears to be safe with very low complication rates.

ACE inhibitors do not induce recombinant human erythropoietin resistance in hemodialysis patients.

Angiotensin-converting enzyme (ACE) inhibitors may exacerbate anemia in patients with chronic renal failure, as well as in dialysis patients. To better answer this question, a prospective, crossover study was conducted to evaluate the effect of ACE inhibitors on recombinant human erythropoietin (rHuEPO) requirements in hemodialysis patients. Patients administered an ACE inhibitor when entering the study remained on this drug for the initial 4 months and were then switched to another antihypertensive agent for 4 more months. Patients not initially administered an ACE inhibitor were switched to lisinopril at 4 months. rHuEPO doses were adjusted using a sliding scale based on weekly laboratory hematocrit values. The inclusion criteria were met by 51 patients undergoing dialysis. Demographics were as follows: 61% were women, 64% were black, 46% had diabetes, average age was 53.2 +/- 13.3 years, and time on hemodialysis was 38.0 +/- 44.5 months. Thirty-three patients completed the study. Hematocrit averaged 32.7% +/- 1.9% while on ACE inhibitor therapy and 33.1% +/- 2.1% off ACE inhibitor therapy (P = 0.217). There was no difference in rHuEPO dose per treatment during each period (3,500 +/- 1,549 U on ACE inhibitor therapy versus 3,312 +/- 1,492 U off ACE inhibitor therapy; P = 0.300). No significant differences were found in degree of blood pressure control or various clinical and laboratory parameters that might be associated with rHuEPO resistance between the two periods. Similarly, no differences were found in hospitalization days, duration of infections, or transfusion requirements. These findings suggest that ACE inhibitors do not contribute to rHuEPO resistance in hemodialysis patients.

Midodrine and cool dialysate are effective therapies for symptomatic intradialytic hypotension.

Intradialytic hypotension (IDH) is a morbid complication of hemodialysis (HD). Both midodrine, an oral selective alpha1 agonist, and cool dialysate have been reported as useful therapies for this problem. We performed this prospective crossover study to compare the efficacy of these two therapies, alone and in combination, for IDH. The study consisted of a control phase and three treatment phases: midodrine phase (10 mg oral dose pre-HD), cool dialysate phase (35.5 degrees C), and combination therapy phase (midodrine, 10 mg, and dialysate temperature, 35.5 degrees C). Each phase consisted of nine consecutive HD treatments. Eleven patients (six men, five women; mean age, 67.5 years) with known symptomatic IDH were studied. This cohort was followed up in terms of blood pressure measurements (pre-HD blood pressure, lowest intradialytic blood pressure, post-HD blood pressure), weights, laboratory values, and interventions for IDH. The lowest intradialytic blood pressures were significantly better with midodrine and cool dialysate compared with the control phase (systolic blood pressure [SBP], 103.9 +/- 4.1 [mean +/- standard error of the mean] and 102.6 +/- 2.9 v 90.6 +/- 2.5 mm Hg, respectively; P < 0.001), as were the post-HD blood pressures (SBP, 116.9 +/- 4.0 and 118.2 +/- 3.5 v 109.0 +/- 2.1 mm Hg; P < 0.01). In addition, the lowest intradialytic blood pressures were significantly better with the combination phase compared with the control phase (SBP, 103.7 +/- 4.2 v 90.6 +/- 2.5 mm Hg; P < 0.001), as were the post-HD blood pressures (SBP, 122.1 +/- 4.6 v 109.0 +/- 2.1 mm Hg; P < 0.01). There was a significant reduction in the number of nursing interventions performed and volume of saline infused for IDH with midodrine and cool dialysate compared with control. There was a trend toward amelioration of hypotensive symptoms with both therapies. Laboratory values, including Kt/V, did not change significantly with either midodrine or cool dialysate. This prospective study shows that both midodrine and cool dialysate are effective therapies for symptomatic IDH. There does not seem to be additional benefit when these two therapies are used in combination.

Extreme hyperphosphatemia and acute renal failure after a phosphorus-containing bowel regimen.

Phosphate intoxication, manifested by hypocalcemic tetany and acute renal failure, may complicate bowel-cleansing preparations which contain phosphate. These preparations are commonly used to prepare patients for various gastrointestinal procedures. Often, patients who receive these regimens are at increased risk of phosphate intoxication from diseases which slow gastrointestinal transit or decrease renal excretion (renal insufficiency). We present a patient who developed oliguric acute renal failure from severe phosphate intoxication associated with a phosphate-containing bowel-cleansing regimen.

Midodrine is effective and safe therapy for intradialytic hypotension over 8 months of follow-up.

Intradialytic hypotension (IDH) is a common and frustrating complication of hemodialysis. Certain end stage renal disease (ESRD) patients recurrently manifest this disabling condition. Both patient-specific factors (autonomic insufficiency, cardiac disease) and dialysis treatment-related factors (ultrafiltration, increased core body temperature) are thought to have significant causative roles. Most therapeutic interventions to date have been either unsuccessful or poorly tolerated. However, recent studies have shown that midodrine, an oral peripheral alpha-1 adrenergic agonist, is an effective and safe therapy for symptomatic IDH in the short-term. We report our experience with the predialysis use of midodrine for IDH in 13 hemodialysis (HD) patients over a 5 to 8 month period. Thirteen patients (8 male, 5 female, mean age 63.9 yrs) with recurrent symptomatic IDH were given midodrine 10 mg orally 30 min before each HD session. Blood pressures (pre-HD BP, lowest intradialytic [ID] BP, post-HD BP) and body weights were tracked for each HD treatment. Values for 10 HD sessions prior to midodrine therapy (Baseline) were compared to values (10 HD sessions each) during the 1st, 5th and 8th month of midodrine therapy. Data were analyzed using ANOVA for repeated measures and paired t-tests, with each patient serving as his/her own control. Patients were monitored for 5 months (n = 13) and 8 months (n = 8), respectively. All lowest intradialytic BPs, post-HD SBPs, and MAPs were significantly improved (p <0.05) on midodrine therapy. This effect was maintained during all periods of follow-up. There was no significant difference in mean albumin, hematocrit, Kt/V, calcium, and sodium between baseline and all periods of follow-up. Mean ultrafiltration volume per HD session was not significantly different than baseline over the course of study. A subjective improvement in hypotensive symptoms was also noted. Importantly, there were no adverse reactions to midodrine in all periods of follow-up. Midodrine appears to be an effective and safe treatment for HD patients with symptomatic IDH, and remains beneficial when used for an extended period of time.

Reduction in arteriovenous graft impairment: results of a vascular access surveillance protocol.

Impairment of hemodialysis (HD) vascular access, remains a frustrating problem for both the patient who possesses an arteriovenous graft (AVG) and the nephrologist who cares for the patient. We instituted a vascular access surveillance protocol intended to detect and correct evolving stenosis in patients with AVGs. The principal screen was the observation of dynamic venous pressure (VP) at a blood flow rate of 200 mL/min during the first 5 minutes of each HD session. If VP at a blood flow rate of 200 mL/min was 140 mm Hg or greater in three of six consecutive readings, recirculation greater than 15% on two observations, graft-arm swelling observed, or prolonged bleeding postdialysis observed, then the patient was referred for angiography and then angioplasty or surgery if a vascular stenosis of greater than 50% was documented. Sixty-four patients with a synthetic AVG comprised the study group. Seventy-two episodes of AVG impairment (56 with stenosis > or = 50% on angiography, 16 with thrombosis) occurred in these patients during the study period. In 63 of 72 impairment episodes, the preceding vascular access screening test was positive. The calculated sensitivity and specificity of the vascular access protocol was 88% and 81%, respectively. Calculation of the sensitivity and specificity for the VP alone was 81% and 85%, respectively. Comparison of the study group with a similar historical control group (55 patients) showed a significantly lower thrombosis rate (P = 0.03; 95% confidence interval [CI], 0.025 to 0.375) in the study group (0.29 thrombotic episodes/graft-year at risk) versus the historical control group (0.49 thrombotic episodes/graft-year at risk). In summary, a vascular access surveillance protocol is a useful tool to predict patients at risk for AVG venous stenosis and/or thrombosis. A dynamic VP of 140 mm Hg or greater appears to be the optimal threshold pressure. A decrease in synthetic AVG thrombosis rate resulted from the use of this surveillance protocol.

Intradialytic hypotension: is midodrine beneficial in symptomatic hemodialysis patients?

Symptomatic hypotension during hemodialysis is a disabling complication in end-stage renal disease (ESRD) patients, especially in certain groups of patients who are at higher risk for this problem. Autonomic dysfunction is thought to play a significant role. We evaluated the efficacy of midodrine, an oral agent with selective alpha-adrenergic agonist activity used in the treatment of neurogenic orthostatic hypotension, on 10 hemodialysis patients with persistent intradialytic hypotension. The patients were given a dose of midodrine (mean dose, 5.5 mg; range, 5 to 10 mg) 30 minutes before each hemodialysis session. We compared blood pressure, pulse, body weight, and laboratory values for 10 consecutive dialysis sessions off and on midodrine therapy. There was a statistically significant improvement in lowest intradialytic systolic blood pressure (from 96.6 to 114.7 mm Hg; P < 0.001), lowest intradialytic diastolic blood pressure (from 53.2 to 59.0 mm Hg; P = 0.002), lowest intradialytic mean arterial pressure (from 67.7 to 77.6 mm Hg; P < 0.001), posthemodialysis systolic blood pressure (from 116.5 to 127.1 mm Hg; P < 0.001), posthemodialysis diastolic blood pressure (from 66.6 to 69.7 mm Hg; P = 0.040), and posthemodialysis mean arterial pressure (from 83.2 to 88.8 mm Hg; P = 0.001) after patients were placed on midodrine. There also was a small but statistically significant decrease in intradialytic pulse rate (from 86.3 to 81 beats/min; P = 0.021) and posthemodialysis pulse rate (from 87.4 to 81.7 beats/min; P = 0.024) after initiation of midodrine therapy. There was no significant difference in any of the prehemodialysis blood pressure measurements or pulse rate off or on midodrine therapy. The improvements in intradialytic and posthemodialysis blood pressure were associated with a uniform subjective improvement in symptoms associated with dialysis hypotension, such as cramps, fatigue, dizziness, and weakness. Other than scalp paresthesia in one patient, no adverse effects were noted. Our results suggest that the administration of a single dose of midodrine before hemodialysis is an effective therapy for intradialytic hypotension. A prospective trial with adequate patient numbers and long-term follow-up would be useful to evaluate this drug's efficacy and safety profile in patients with ESRD.

Hyperkalemia in the elderly: drugs exacerbate impaired potassium homeostasis.

OBJECTIVE: To review the pathophysiology underlying the predisposition to hyperkalemia in the elderly; the medications that disrupt potassium balance and promote the development of hyperkalemia in the elderly; the prevention of hyperkalemia in elderly patients treated with potassium-altering medications; and the appropriate management of hyperkalemia when it develops. METHODS AND MAIN RESULTS: A MEDLINE search of the literature (1966-1996) using the terms hyperkalemia, drugs, elderly, and treatment was conducted and pertinent review articles, textbooks, and personal files were consulted. Elderly subjects appear to be predisposed to the development of hyperkalemia on the basis of both innate disturbances in potassium homeostasis and comorbid disease processes that impair potassium handling. Hyperkalemia in the elderly is most often precipitated by medications that impair cellular uptake or renal disposal of potassium. This electrolyte disorder is best prevented by recognition of at-risk physiology in the aged, avoidance of therapy with certain high-risk medications, and monitoring of plasma potassium concentration and renal function at intervals appropriate for the medication prescribed. Management of hyperkalemia entails identification of the clinical manifestations of severe hyperkalemia, stabilization of cardiac tissue, promotion of cellular potassium uptake, and ultimately removal of potassium from the body. CONCLUSIONS: Geriatric patients should be considered at risk of developing hyperkalemia, especially when they are prescribed certain medications. Potassium levels should be monitored at appropriate intervals when these patients are treated with potassium-altering medications. Appropriate management of hyperkalemia in the elderly can avoid life-threatening neuromuscular and cardiac complications.

Bone marrow transplant nephropathy: a case report and review of the literature.

Bone marrow transplantation can be complicated by renal failure resulting from a variety of causes. Early renal injury most often results from infection and its subsequent treatment with nephrotoxic medications. Late renal injury after bone marrow transplantation is characterized by a syndrome similar to the hemolytic uremic syndrome. This renal syndrome, called "bone marrow transplant nephropathy," is thought to evolve from the late effects of radiation therapy and cytotoxic chemotherapy on the kidney. In this article, a case of bone marrow transplant nephropathy and a review of the clinical and pathologic features are presented.

Angiotensin-converting enzyme inhibitor therapy in chronic hemodialysis patients: any evidence of erythropoietin resistance?

Exacerbation of anemia associated with angiotensin-converting enzyme (ACE) inhibitor therapy has been noted to occur in patients with chronic renal failure, end-stage renal disease, and renal transplantation. Angiotensin-converting enzyme inhibitors appear to cause anemia through induction of decreased red blood cell production. There are data suggesting that ACE inhibitors may impair erythropoiesis via either suppression of angiotensin-mediated erythropoietin (EPO) production or bone marrow response to EPO. Patients on chronic hemodialysis receive recombinant human EPO (rHuEPO) for therapy of anemia and may also receive an ACE inhibitor for hypertension or congestive heart failure. We undertook a retrospective study to evaluate whether patients treated with ACE inhibitors developed a more severe anemia or required a higher dose of rHuEPO to maintain a similar hematocrit. Ninety-five of 108 chronic hemodialysis patients met study criteria (hemodialysis for 4 months and no treatment with an ACE inhibitor for at least 4 months = group 1; therapy with an ACE inhibitor for at least 4 months = group 2). Forty-eight patients (group 1, n = 24; group 2, n = 24) were available for analysis after exclusion for a variety of factors. There was no difference between the two groups in terms of baseline characteristics, number of blood transfusions or hospital days, or other laboratory parameters. There was no statistically significant difference in average hematocrit between group 1 (33.5% +/- 3.9%) and group 2 (32.6% +/- 1.6%). Similarly, no significant difference was observed for the average rHuEPO dose/treatment between group 1 (3,272 +/- 1,532 IU/treatment; 50.69 +/- 26.94 IU/kg/treatment) and group 2 (3,401 +/- 1,009 IU/treatment; 52.87 +/- 19.38 IU/kg/treatment). These results suggest that ACE inhibitors do not significantly induce more severe anemia or alter rHuEPO response in chronic hemodialysis patients.

A middle-aged woman with back and flank pain.

Xanthogranulomatous pyelonephritis is an uncommon variant of chronic pyelonephritis that predominantly affects middle-aged women. Patients usually present with fever, back or flank pain, flank mass, and the constitutional symptoms of fatigue, malaise, weight loss, and anorexia. Rarely, they may present with a draining sinus. There is usually a history of urinary tract infection, obstruction, or instrumentation. Other abnormalities include anemia, leukocytosis, abnormal liver enzymes, pyuria, and hematuria. Mild azotemia may be present, but frank renal failure is rare. Urine and renal tissue cultures are frequently positive. The most commonly isolated bacterial pathogens are P. mirabilis and E. coli, but other organisms have also been implicated. A CT scan is the best radiologic imaging technique to discover the extent of inflammation as well as any involvement of adjacent structures. Lipid-laden macrophages called xanthoma cells characterize the disease at the microscopic level. Nephrectomy is curative. Careful preoperative evaluation will guide surgical planning in choosing an approach that provides adequate exposure of the affected tissue and facilitates subsequent care of the patient.

Trimethoprim-sulfamethoxazole: hyperkalemia is an important complication regardless of dose.

Trimethoprim-sulfamethoxazole is a frequently prescribed antibiotic with a wide spectrum of antimicrobial activity. As a result of the increasing number of AIDS patients requiring therapy for Pneumocystis carinii pneumonia, high dose trimethoprim-sulfamethoxazole use had dramatically increased. A previously unreported and potentially lethal adverse reaction associated with high dose trimethoprim-sulfamethoxazole therapy, hyperkalemia, subsequently developed. Recognition of this potassium disorder led to investigation and description of the mechanism by which trimethoprim-sulfamethoxazole induced hyperkalemia. Trimethoprim was found to act like the potassium-sparing diuretic amiloride and reduce renal potassium excretion. Subsequent to this work, a handful of cases noted the development of hyperkalemia with standard dose trimethoprim-sulfamethoxazole in elderly patients without evidence of an obvious defect in potassium homeostasis. A prospective surveillance study of patients treated with standard dose trimethoprim-sulfamethoxazole as compared to similar controls treated with other antibiotics confirmed the rise in potassium concentration associated with trimethoprim-sulfamethoxazole therapy. Patients with mild renal insufficiency were the only group at significant risk for more severe hyperkalemia. Hence, trimethoprim-sulfamethoxazole therapy can be complicated by hyperkalemia regardless of the dose employed.

Diabetic nephropathy: a comprehensive approach.

By the time the traditional dipstick test shows excess urinary albumin, glomerular damage may be beyond repair and nephrotic syndrome virtually guaranteed. More sensitive assays provide earlier warning, allowing the clinician to institute a surveillance and antihypertensive program that--along with dietary glycemic control--can stave off disease progression.

Interrelationships among quinidine, amiloride, and lithium as inhibitors of the renal Na+-H+ exchanger.

We examined the effects of quinidine, amiloride and Li+ on the kinetics of Na+-H+ exchange in microvillus membrane vesicles isolated from the rabbit renal cortex. Quinidine reversibly inhibited the initial rate of Na+-H+ exchange (I50 200 microM). The plot of 1/V versus [quinidine] was curvilinear, with Hill coefficient greater than 1.0, indicating that the drug interacts at two or more inhibitory sites or at a single site on at least two different conformations of the transporter. Quinidine decreased the Vmax for Na+-H+ exchange and increased the Km for Na+, indicating a mixed-type mechanism of inhibition. In contrast, plots of 1/V versus [amiloride] and 1/V versus [Li+] were linear, indicating single inhibitory sites; amiloride and Li+ each increased the Km for Na+ with no effect on Vmax, indicating a competitive mechanism of inhibition. Addition of Li+ increased the intercept with no change in slope of the 1/V versus [amiloride] plot, indicating that Li+ and amiloride are mutually exclusive inhibitors of Na+-H+ exchange. Addition of quinidine increased the slopes of the plots of 1/V versus [amiloride] and 1/V versus [Li+], indicating that the binding of quinidine is not mutually exclusive with the binding of amiloride and Li+. Results from this and previous studies are consistent with the concept that the inhibitor amiloride and the transportable substrates Na+, H+, Li+, and NH+4 all mutually compete for binding to a single site, the external transport site of the renal Na+-H+ exchanger. However, our findings indicate that quinidine interacts with the Na+-H+ exchanger on at least one additional site that is not shared by Na+, Li+, or amiloride.

The plasma membrane sodium-hydrogen exchanger and its role in physiological and pathophysiological processes.

The plasma membranes of most if not all vertebrate cells contain a transport system that mediates the transmembrane exchange of sodium for hydrogen. The kinetic properties of this transport system include a 1:1 stoichiometry, affinity for lithium and ammonium ion in addition to sodium and hydrogen, the ability to function in multiple 1:1 exchange modes involving these four cations, sensitivity to inhibition by amiloride and its analogues, and allosteric regulation by intracellular protons. The plasma membrane sodium-hydrogen exchanger plays a physiological role in the regulation of intracellular pH, the control of cell growth and proliferation, stimulus-response coupling in white cells and platelets, the metabolic response to hormones such as insulin and glucocorticoids, the regulation of cell volume, and the transepithelial absorption and secretion of sodium, hydrogen, bicarbonate and chloride ions, and organic anions. Preliminary evidence raises the possibility that the sodium-hydrogen exchanger may play a pathophysiological role in such diverse conditions as renal acid-base disorders, essential hypertension, cancer, and tissue or organ hypertrophy. Thus, future research on cellular acid-base homeostasis in general, and on plasma membrane sodium-hydrogen exchange in particular, will enhance our understanding of a great variety of physiological and pathophysiological processes.