Search

Patients on maintenance dialysis may be immunocompromised and have comorbidities that modulate the response to coronavirus disease 2019 (COVID-19) vaccines. We conducted a quality improvement project to characterize the antibody response to COVID-19 vaccination in two dialysis clinics in Arizona

Introduction: Home hemodialysis remains underutilized despite observational data indicating more favorable outcomes with home compared with in‐center hemodialysis. The Tablo Hemodialysis system is designed to be easy to learn and use and to facilitate adoption of home hemodialysis. The objective of the current investigational device exemption (IDE) study was to evaluate the safety and efficacy of Tablo managed in‐center by health care professionals and in‐home by patients and/or caregivers. Methods: A prospective, multicenter, open‐label, crossover trial comparing in‐center and in‐home hemodialysis using Tablo. There were 4 treatment periods during which hemodialysis was prescribed 4 times per week: 1‐week Run‐In, 8‐week In‐Center, 4‐week Transition, and 8‐week In‐Home. The primary efficacy endpoint was weekly standard Kt/Vurea ≥ 2.1. The secondary efficacy endpoint was delivery of ultrafiltration (UF) within 10% of prescribed UF. We collected safety and usability data. Findings: Thirty participants enrolled and 28 completed all trial periods. Adherence to the protocol requirement of 4 treatments per week was 96% in‐center and 99% in‐home. The average prescribed and delivered session lengths were 3.4 hours for both the In‐Center and the In‐Home periods. The primary efficacy endpoint for the intention‐to‐treat cohort was achieved in 199/200 (99.5%) of measurements during the In‐Center period and 168/171 (98.3%) In‐Home. The average weekly standard Kt/Vurea was 2.8 in both periods. The secondary efficacy UF endpoint was achieved in the ITT cohort in 94% in both in‐center and in‐home. Two prespecified adverse events (AEs) occurred during the In‐Center period and 6 in the In‐Home period. None of the AEs were deemed by investigators as related to Tablo. The median resolution time of alarms was 8 seconds in‐center and 5 seconds in‐home. Conclusion: Primary and secondary efficacy and safety endpoints were achieved during both In‐Center and In‐Home trial periods. This study confirms that Tablo is safe and effective for home hemodialysis use.

Introduction Recently published results of the investigational device exemption (IDE) trial using the Tablo hemodialysis system confirmed its safety and efficacy for home dialysis. This manuscript reports additional data from the Tablo IDE study on the training time required to be competent in self‐care, the degree of dependence on health care workers and caregivers after training was complete, and participants' assessment of the ease‐of‐use of Tablo. Methods We collected data on the time required to set up concentrates and the Tablo cartridge prior to treatment initiation. We asked participants to rate system setup, treatment, and takedown on a Likert scale from 1 (very difficult) to 5 (very simple) and if they had required any assistance with any aspect of treatment over the prior 7 days. In a subgroup of 15 participants, we recorded the number of training sessions required to be deemed competent to do self‐care dialysis. Findings Eighteen men and 10 women with a mean age of 52.6 years completed the study. Thirteen had previous self‐care experience using a different dialysis system. Mean set up times for the concentrates and cartridge were 1.1 and 10.0 minutes, respectively. Participants with or without previous self‐care experience had similar set‐up times. The mean ease‐of‐use score was 4.5 or higher on a scale from 1 to 5 during the in‐home phase. Sixty‐five percent required no assistance at home and on average required fewer than four training sessions to be competent in managing their treatments. Results were similar for participants with or without previous self‐care experience. Conclusions Participants in the Tablo IDE trial were able to quickly learn and manage hemodialysis treatments in the home, found Tablo easy to use, and were generally independent in performing hemodialysis.

This is the first description of functional immunoassay technology (FIT), which as a diagnostic tool has broad application across the whole spectrum of physiological measurements. In this paper, FIT is used to measure the renal clearance of an ultra low-dose administration of a clinically available contrast reagent for the purpose of obtaining an accurate glomerular filtration rate (GFR) measurement. Biomarker-based GFR estimates offer convenience, but are not accurate and are often misleading. FIT overcomes previous analytic barriers associated with obtaining an accurate GFR measurement. We present the performance characteristics of this diagnostic test and demonstrate the method by directly comparing GFR values obtained by FIT to those obtained by an FDA approved nuclear test in 20 adults. Two subjects were healthy volunteers and the remaining 18 subjects had diagnosed chronic kidney disease, with 12 being kidney transplant recipients. Measured GFR values were calculated by the classic UV/P method and by the blood clearance method. GFR obtained by FIT and the nuclear test correlated closely over a wide range of GFR values (10.9–102.1 ml·min−1·1.73 m−2). The study demonstrates that FIT-GFR provides an accurate and reproducible measurement. This nonradioactive, immunoassay-based approach offers many advantages, chiefly that most laboratories already have the equipment and trained personnel necessary to run an ELISA, and therefore this important diagnostic measurement can more readily be obtained. The FIT-GFR test can be used throughout the pharmaceutical development pipeline: preclinical and clinical trials.

Background. The renal effects of cyclooxygenase-2 (COX-2) inhibitors have been incompletely elucidated, and acute renal failure (ARF) due to COX-2 inhibitors has been reported. Methods. In order to determine the causes of ARF and hyperkalaemia in five patients during COX-2 inhibitor therapy, we carefully analysed case studies of consecutive in-patients or out-patients referred to our Renal Division over a 6-month period for ARF and hyperkalaemia who had recently received COX-2 inhibitors. Results. ARF developed 2–3 weeks after COX-2 inhibitor therapy in five patients. The ARF was consistent with pre-renal azotaemia from renal hypoperfusion. Four patients were receiving the loop diuretic, furosemide. Four patients developed hyperkalaemia and decreased serum bicarbonate despite diuretic therapy, and one patient had changes in plasma renin activity and aldosterone levels consistent with reversible hyporeninaemic hypoaldosteronism. Renal failure was reversible after discontinuation of diuretics and COX-2 inhibitors. Conclusions. COX-2 inhibitors may cause reversible ARF and hyperkalaemia in patients with oedematous conditions treated with low sodium diets and loop diuretics.

Studies performed at large metropolitan medical centers have reported an increasing incidence of idiopathic focal segmental glomerulosclerosis (FSGS) in adults. To determine whether a similar trend occurs in small urban and rural communities and to determine the role of race in these observations, we reviewed the patient records of all adults who underwent renal biopsies at our institution over the 20-year period from 1974 to 1994. The patients were grouped for analysis in 5-year intervals, 1975 to 1979, 1980 to 1984, 1985 to 1989, and 1990 to 1994, for the following diagnoses: FSGS, membranous nephropathy (MN), minimal change nephropathy (MCN), membranoproliferative glomerulonephritis (MPGN), immunoglobulin A (IgA) nephropathy, chronic glomerulonephritis, diabetic nephropathy, hypertensive nephrosclerosis, and chronic interstitial nephritis. Patients with secondary causes for these lesions were excluded. The relative frequency of FSGS increased from 13.7% during 1975 to 1979 to 25% during 1990 to 1994 (P < 0.05). The relative frequency of MN decreased from 38.3% during 1975 to 1979 to 14.5% during 1990 to 1994 (P < 0.01). There were no changes in the frequencies of MCN, MPGN, IgA nephropathy, chronic glomerulonephritis, diabetic nephropathy, hypertensive nephrosclerosis, or chronic interstitial nephritis over the 20-year period. However, there was a significant increase in the percentage of blacks with FSGS, from 0% in 1975 to 1979 to 22.6% in 1990 to 1994, and an increased percentage of Hispanics with FSGS, from 0% in 1975 to 1979 to 21.3% in 1990 to 1994 (P < 0.05). The modest increase in whites with FSGS did not reach statistical significance. The incidence of MN in blacks and whites decreased over the 20-year period. In the last 5 years, 15 patients per year had FSGS compared with 7 patients per year with MN (P < 0.05). No changes in age or sex between groups or over time accounted for these results. We conclude that FSGS is now diagnosed twice as often as MN and is the most common idiopathic glomerular disease at our hospital. Reasons for this increase include the emergence of FSGS in both Hispanics and blacks, with a modest increase of FSGS in whites. The increase in FSGS in the three most common races in our community suggests that factors other than genetic, perhaps environmental, have a role in the pathogenesis of FSGS.

Background. Two patients underwent cadaver transplantation with kidneys from a donor with a history of World Health Organization Class IV/V lupus nephritis, and we report their clinical and pathological outcome. Methods. The donor had a diagnosis of lupus nephritis made by renal biopsy 5 years before donation. At the time of donation, a biopsy was performed on the donor and on one of the recipients at 2 months and 1 year after the transplant. Results. Both recipients underwent uneventful renal transplantation. On the first postoperative day, the donor’s final pathological results became available. Although the frozen section seemed to be quite benign, the permanent sections revealed World Health Organization Class II/V lupus nephritis, with full house immunofluorescence and multiple electron dense deposits. Biopsies were performed on recipient #2 at 8 weeks and 1 year after the transplant. These revealed marked diminution followed by complete resolution of all tubular reticular structures and deposits as well as immunofluorescent activity. Both recipients remain with normal renal function and urinalysis at 3 years after the transplant. Conclusion. Although a history of clinically significant renal disease has been considered an absolute contraindication to kidney donation, with appropriate workup and caution, select patients may still be considered, which would increase the potential donor pool.

Chronic kidney disease (CKD) is a growing problem among the elderly. Early detection is considered essential to ensure proper treatment and to avoid drug toxicity, but detection is challenging because elderly patients with CKD often have normal serum creatinine levels. We hypothesized that most cases of CKD in the elderly would go undetected, resulting in inappropriate prescribing.To determine whether recognition of CKD is associated with more appropriate treatmentRetrospective chart reviewAll patients aged/=65 years with a measured serum creatinine in the past 3 years at 2 inner city academic health centers.Estimated glomerular filtration rate (eGFR) calculated using the Modified Diet in Renal Disease equation, and for patients with eGFR60, documentation of CKD by the provider, diagnostic testing, nephrology referral and prescription of appropriate or contraindicated medications.Of 814 patients with sufficient information to estimate eGFR, 192 (33%) had moderate (eGFR60 mL/min) and 5% had severe (eGFR30 mL/min) CKD. Providers identified 38% of moderate and 87% of severe CKD. Compared to patients without recognized CKD, recognized patients were more likely to receive an ACE/ARB (80% vs 61%, p = .001), a nephrology referral (58% vs 2%, p.0001), or urine testing (75% vs 47%, p.0001), and less likely to receive contraindicated medications (26% vs 40%, p = .013).Physicians frequently fail to diagnose CKD in the elderly, leading to inappropriate treatment. Efforts should focus on helping physicians better identify patients with low GFR.

Background: Potassium-rich cardioplegia has advantages over other cardioplegic solutions in preserving the myocardium during cardiopulmonary bypass, but it is avoided in patients with renal failure because of hyperkalemia. Methods: We first determined the ability of intraoperative hemodialysis (IHD) to remove potassium during cardiopulmonary bypass with potassium-rich cardioplegia in 9 patients by measuring potassium levels in all dialysate and urine. We then studied 24 patients with renal failure, grouped with the 9 previous patients, to assess safety, rebound hyperkalemia, and patient outcome with this technique. Results: In the first phase, 9 patients were administered 128 ± 11 mmol of potassium in potassium-rich cardioplegia, and IHD removed 157 ± 23 mmol. Urinary potassium excretion was only 10 ± 3 mmol. Potassium removal occurred at a rate of 1.25 mmol/min with 0-mEq/L (mmol/L) potassium dialysate and a rate of 0.75 mmol/min with 3.0-mEq/L (mmol/L) potassium dialysate. In all 33 patients, successful initiation of cardiac rhythm occurred after cardiopulmonary bypass, and 5 patients had cardiac arrhythmias possibly from hypokalemia. In the next 24 hours, 5 dialysis-dependent patients developed hyperkalemia (potassium > 5.2 mEq/L [mmol/L]) requiring hemodialysis. Postoperative hemodialysis was delayed 2 to 3 days in the other patients. The overall death rate was 24% at 30 days. Conclusion: IHD effectively and safely removes potassium administered during potassium-rich cardioplegia during cardiopulmonary bypass in patients with renal failure and prevents postoperative hyperkalemia in the majority of patients. Overall mortality in patients with acute and chronic renal failure undergoing cardiac surgery is high irrespective of control of potassium balance in these patients.

Since the introduction of cylcosporine into clinical use, a major area of concern within the transplant community has been the fear of chronic nephrotoxicity. Although progressive renal damage does appear to occur in native kidneys of heart and liver transplant patients receiving cyclosporine, it has been our contention that its use is not a major cause of deterioration in renal allografts. We therefore undertook a study of 91 consecutive renal transplants performed over a three-year period with a minimum graft survival of 1 year and a follow-up of 7–9 years. Serial serum creatinine values, iothalamate clearances and cyclosporine levels were obtained at 3 months after transplantation and yearly thereafter. Biopsies were performed on all grafts that had failed as well as on the majority of patients with deteriorating renal function, and were interpreted by two nephropathologists. As measured by iothalamate clearances, 65 % of the patients in this series exhibited absolutely stable renal function despite the maintenance of cyclosporine levels of more than 200 ng/ml for 7–9 years. Since these stable patients did not reveal any decline in renal function, it therefore follows that they did not experience chronic cyclosporine nephrotoxicity. Furthermore, none of the patients with declining renal function or with failed grafts showed any evidence of nephrotoxicity on biopsy. Chronic cyclosporine nephrotoxicity may be a cause of declining function or graft loss with renal transplant recipients, but if so, it is exceedingly rare.

Aerosolized beta2-agonists have been associated with increased morbidity in asthmatics. These drugs cause transient increases in heart rate and decreases in serum potassium levels after these drugs are first utilized. This study is designed to elucidate whether beta-adrenergic tolerance to the hemodynamic, cardiac, and electrolyte effects of inhaled terbutaline occurs during 14 days of maintenance therapy.Eight patients with stable asthma weaned off beta2-agonist therapy were studied in a randomized, double-blinded, placebo-controlled study utilizing aerosolized terbutaline, 400 microg q6h. Hemodynamic measurements and M-mode echocardiography were performed before and 15 and 30 min after the initial dose of terbutaline or placebo and after a dose of aerosolized terbutaline after 14 days of aerosolized terbutaline maintenance therapy. Holter monitors were worn on the first day of placebo or terbutaline therapy and on day 14 of terbutaline therapy. Plasma potassium, bicarbonate, and glucose levels, pH, renin activity, and serum insulin and aldosterone levels were measured before and after 24 and 48 h after terbutaline or placebo therapy and after 14 days of aerosolized terbutaline maintenance therapy.Terbutaline increased cardiac index and decreased systemic vascular resistance greater after 14 days of therapy compared with the first dose (5.2+/-0.5 vs 4.4+/-0.6 L/min/m2; p0.05; and 760+/-62 vs 1,016+/-118 dyne x s x cm(-5), p0.01). After 14 days of terbutaline therapy, the mean maximum heart rate and number of episodes of heart rate100 beats/min were higher compared with the other study day (p0.05). Plasma potassium level decreased from 4.29+/-0.09 to 3.65+/-0.16 mmol/L after 24 h of terbutaline and to 3.90+/-0.11 mmol/L after 48 h. Plasma potassium level returned to baseline after 14 d of terbutaline therapy. Plasma glucose and serum insulin levels rose significantly 24 h and 48 h after terbutaline and returned to baseline after 14 d of terbutaline therapy. Serum aldosterone level decreased significantly as serum potassium level decreased in the first 48 h of terbutaline therapy but returned to baseline levels after 14 d of terbutaline.Cardiovascular beta2-receptors in patients with stable asthma do not develop tolerance to the effects of low-dose aerosolized terbutaline after 14 days of maintenance therapy. In contrast, the homeostatic mechanisms regulating serum potassium develop tolerance to low-dose terbutaline maintenance therapy. Lack of cardiovascular tolerance to maintenance doses of aerosolized beta2-agonists may be important in increased morbidity if excessive amounts of these drugs are administered during asthma exacerbations.

We reviewed 31 episodes of gram-positive peritonitis that occurred in our peritoneal dialysis population between 1990 and 1993 in an attempt to identify the risk factor(s) for peritonitis relapse. All patients were treated with 4 weekly doses of intravenous vancomycin. Vancomycin doses no. 1 and 2 were based on body weight (15 mg/kg with a 1-g minimum); vancomycin doses no. 3 and 4 were adjusted in an attempt to maintain the trough serum vancomycin level at greater than 12 mg/L. Nine peritonitis episodes complicated by a relapse were identified. Peritonitis episodes preceding a relapse were similar to relapse-free episodes with respect to patient age, diabetes, peritoneal dialysis modality, duration of peritoneal dialysis treatment, residual urea clearance, peritoneal fluid cell count, causative organism, and weekly vancomycin dose. However, cumulative 4-week mean trough vancomycin levels were consistently lower during peritonitis episodes preceding a relapse (7.8 +/- 0.6 mg/L during relapse-prone episodes v 13.7 +/- 0.9 mg/L during relapse-free episodes; P = 0.0004). Furthermore, relapses developed during nine of 14 peritonitis episodes demonstrating a 4-week mean trough vancomycin level less than 12 mg/L compared with zero of 17 episodes with a 4-week trough level greater than 12 mg/L (P < 0.05). The detection of a low initial 7-day trough vancomycin level also was a useful marker for subsequent peritonitis relapse. In 13 peritonitis episodes associated with an initial trough level less than 9 mg/L, nine were complicated by a relapse.(ABSTRACT TRUNCATED AT 250 WORDS)

Angiotensin-converting enzyme (ACE) inhibitor therapy has recently been shown to be effective in the treatment of post-renal transplant erythrocytosis (PTE). In an attempt to assess the effect of drug treatment on serum erythropoietin level, glomerular filtration rate, and urinary protein excretion, we prospectively evaluated 8 consecutive cadaveric renal transplant recipients with PTE treated with ACE inhibitor therapy for 3 months. In response to ACE inhibition, the mean hematocrit (HCT) value decreased from 53.7 +/- 0.6% before treatment to 42.7 +/- 2.2% at the conclusion of the study (p = 0.03). However, 1 patient failed to respond to ACE inhibition (HCT > 50%), and 2 patients with PTE developed anemia (HCT < 35%) while maintained on drug treatment. Although the mean serum erythropoietin level decreased during ACE inhibition (from 22.8 +/- 8.4 to 9.4 +/- 5.3 mU/ml; p = 0.06), a consistent change in individual erythropoietin levels was not identified. At the conclusion of the study, the serum erythropoietin levels were undetectable in 4 patients, decreased in 1, unchanged in 2, and increased in the only patient with PTE who failed to respond to drug treatment. All patients tolerated the ACE inhibitor therapy without developing cough or hyperkalemia. In addition, serum creatinine levels, 125I-iothalamate clearances, and mean arterial blood pressures were unchanged throughout the study. Microalbuminuria (spot urinary albumin/creatinine ratio between 30 and 200 mg/g) developed in 5 patients with PTE and coincided with the onset of erythrocytosis (25.2 +/- 7 mg/g before PTE and 76.3 +/- 36.7 mg/g at the time of PTE detection).(ABSTRACT TRUNCATED AT 250 WORDS)

Measurement of the glomerular filtration rate (GFR) in patients with chronic renal disease has recently assumed increasing importance. Responsibility for this evolutionary change can be directly traced to our understanding of the limitations of plasma creatinine and creatinine clearance as markers of GFR (1,2) and the need for accurate and precise quantitation of GFR as potential therapies for progressive renal disease are being evaluated (3). Traditional methods for measurement of GFR are accurate but cumbersome and inconvenient for patients. Newer methods are sometimes less accurate but offer advantages of reproducibility and are more readily implemented. In this review, we discuss the attributes and limitations of different methods and markers for the assessment of GFR with an emphasis on clearance using radioisotopic markers.

We studied a patient with alcoholic acidosis and an increased osmolal gap. Ethyl alcohol and other compounds that are known to increase serum osmolality in alcoholics were not detected. However, the levels of glycerol, acetone, and the acetone metabolites acetol and 1,2-propanediol were increased in the serum of this patient. On admission and 3 and 7 hours after admission, the combined serum osmolality of glycerol, acetone, acetol, and 1,2-propanediol accounted for 48%, 92%, and 62% of the increase in the osmolal gap above the highest normal level of 10 mOsm/kg H 2 O. The disappearance of the osmolal gap correlated with the correction of the acidosis and the concomitant reduction in serum glycerol and acetone levels. Elevations of endogenous glycerol, acetone, and acetone metabolite levels should now be added as causes for an increased osmolal gap in the alcoholic patient. Ingestion of toxic alcohols can no longer be assumed to be the only cause for an increased osmolal gap in alcoholic patients. (Arch Intern Med. 1993;153:2377-2380)

Although acute rejection (AR) has been shown to correlate with decreased long-term renal allograft survival, we have noted AR in recipients who subsequently had stable function for more than 5 years. We reviewed 109 renal graft recipients with a minimum of 1 year graft survival and follow-up of 5–8 years. Post-transplant sodium iothalamate clearances (IoCl) measured at 3 months and yearly thereafter were used to separate recipients into 2 groups. In 61 patients (stable group), there was no significant decrease ( > 20 % reduction in IoCl over 2 consecutive years) in IoCl. Forty-eight patients had significant declines in IoCl (decline group). Groups were compared for incidence, severity, timing, and completeness of reversal of AR. Rejection was considered completely reversed if the post-AR serum creatinine (Scr) returned to or below the pre-AR nadir Scr after antirejection therapy. The incidence of AR was not significantly different between groups (47 % vs 52 %). A trend toward a lower mean number of AR episodes per patient was noted in the stable group (0.69 vs 1.04, P = 0.096), but the timing of AR was not different. Steroid-resistant AR occurred in approximately 25 % of both groups. A striking difference was seen in complete reversal of AR, with the stable group having 100 % (42/42 episodes of AR in 29 patients) complete reversal whereas only 32 % (8/25) of the patients in the decline group had complete reversal (P < < 0.001). Of 8 declining patients with complete reversal, graft loss was due to chronic rejection (CR) in only 3. Seventeen declining patients had incomplete reversal of AR, and 82 % (14/17) lost their grafts to CR. Overall, only 8 % (3/37) of the recipients with complete reversal of AR developed CR. No patients with incompletely reversed AR had stable long-term function as measured by IoCl. AR is not invariably deleterious to long-term renal graft function if each episode of AR can be completely reversed.