Search

Introduction: Atrial fibrillation (AF) is common in patients with kidney failure on hemodialysis (KF-HD). We determined both AF incidence and burden in patients with KF-HD using implantable loop recorder (ILR) monitoring. Methods: Patients with KF-HD were enrolled and received an ILR. In 6 monitoring months, the incidence of AF events lasting ≥6 minutes was captured. Demographic, clinical, and dialysis characteristics were collected, and associations with incident AF were estimated using negative binomial regression models and expressed as incidence rate ratios and 95% CIs. Results: We enrolled 66 patients with KF-HD (mean age = 56 years, 70% male); 59 (90%) were without previously diagnosed AF. AF lasting ≥6 minutes was detected in 18 of 59 subjects (31%) without previously diagnosed AF and in 5 of 7 subjects (71%) with a previous AF diagnosis. Among the 23 with detected AF, episodes were present on 16% of patient days. Although 14 of 23 patients (61%) had AF on 2.5 vs. 2.5 mEq/l: incidence rate ratio = 0.62; 95% CI, 0.48–0.80) was associated with lower AF risk whereas higher dialysate bicarbonate concentrations (>35 vs. 35 mEq/l: incidence rate ratio = 3.18; 95% CI, 1.13–8.94) were associated with higher AF risk. Conclusion: New AF was detected in approximately one-third of patients with KF-HD. AF affects a substantial proportion of patient days and may be an underappreciated cause of stroke in KF-HD.

Introduction A C5 polymorphism (rs17611, 2404G>A) exists where the G allele associates with enhanced C5a-like production by neutrophil elastase. This cohort study investigated the influence of this polymorphism as a risk factor for lupus nephritis (LN), and on C5a and membrane attack complex (MAC) levels in LN during flare. Methods A cohort of lupus patients (n = 155) was genotyped for the 2404G>A polymorphism. A longitudinal LN subset (n = 66) was tested for plasma and urine levels of C5a and MAC 4 and/or 2 months before and at nonrenal or LN flare. Results The 2404G allele and 2404-GG genotype were associated with LN in black, but not white, lupus patients. In the longitudinal cohort, neither urine nor plasma C5a levels changed at nonrenal flare regardless of 2404G>A genotype or race. Urine (but not plasma) C5a levels increased at LN flare independent of race, more so in 2404-GG patients where 8 of 30 LN flares exhibited very high C5a levels. Higher proteinuria and serum creatinine levels also occurred in these eight flares. Urine (but not plasma) MAC levels also increased at LN flare in 2404-GG patients and correlated with urine C5a levels. Conclusions The C5 2404-G allele/GG genotype is a potential risk factor for LN uniquely in black lupus patients. The GG genotype is associated with sharp increases in urine C5a and MAC levels in a subset of LN flares that correspond to higher LN disease indices. The lack of corresponding changes in plasma suggests these increases reflect intrarenal complement activation., Graphical abstract

Introduction Narsoplimab is a human monoclonal antibody against mannan-associated lectin-binding serine protease−2 (MASP-2). Now in a phase 3 study, narsoplimab was evaluated in a staged phase 2 study assessing safety and effectiveness in high-risk patients with IgA nephropathy (IgAN). Methods Substudy 1 was a single-arm open-label study of 12 weekly infusions and tapered corticosteroids, with 6 weeks of follow-up. In substudy 2, patients were randomized 1:1 to receive a course of treatment consisting of once-weekly narsoplimab or vehicle infusions for 12 weeks. After 6 weeks of follow-up, both substudy 2 groups could continue in an open-label extension, receiving 1 or more narsoplimab courses at the investigator’s discretion. Results The most commonly reported adverse events (AEs) included headache, upper respiratory infection, and fatigue. Most AEs were mild or moderate and transient. No treatment-related serious AEs were reported. All 4 patients who were enrolled in substudy 1 had reductions in 24-hour urine protein excretion (UPE) at week 18, ranging from 54% to 95% compared with baseline. In substudy 2, the vehicle and narsoplimab groups had similar proteinuria reductions at week 18. Eight patients (3 vehicle, 5 narsoplimab) continued in the dosing extension; all received narsoplimab. Median reduction in 24-hour UPE in these 8 patients was 61.4% at 31 to 54 weeks postbaseline. Estimated glomerular filtration rates (eGFR) remained stable in both substudies. Conclusion This interim analysis suggests that narsoplimab treatment is safe, is well tolerated, and may result in clinically meaningful reductions in proteinuria and stability of eGFR in high-risk patients with advanced IgAN., Graphical abstract

Approximately 9 months of the severe acute respiratory syndrome coronavius-2 (SARS-CoV-2 [COVID-19]) spreading across the globe has led to widespread COVID-19 acute hospitalizations and death. The rapidity and highly communicable nature of the SARS-CoV-2 outbreak has hampered the design and execution of definitive randomized, controlled trials of therapy outside of the clinic or hospital. In the absence of clinical trial results, physicians must use what has been learned about the pathophysiology of SARS-CoV-2 infection in determining early outpatient treatment of the illness with the aim of preventing hospitalization or death. This article outlines key pathophysiological principles that relate to the patient with early infection treated at home. Therapeutic approaches based on these principles include 1) reduction of reinoculation, 2) combination antiviral therapy, 3) immunomodulation, 4) antiplatelet/antithrombotic therapy, and 5) administration of oxygen, monitoring, and telemedicine. Future randomized trials testing the principles and agents discussed will undoubtedly refine and clarify their individual roles; however, we emphasize the immediate need for management guidance in the setting of widespread hospital resource consumption, morbidity, and mortality.

Sudden death is one of the more frequent causes of death for hemodialysis patients, but the underlying mechanisms, contribution of arrhythmia, and associations with serum chemistries or the dialysis procedure are incompletely understood. To study this, implantable loop recorders were utilized for continuous cardiac rhythm monitoring to detect clinically significant arrhythmias including sustained ventricular tachycardia, bradycardia, asystole, or symptomatic arrhythmias in hemodialysis patients over six months. Serum chemistries were tested pre- and post-dialysis at least weekly. Dialysis procedure data were collected at every session. Associations with clinically significant arrhythmias were assessed using negative binomial regression modeling. Sixty-six patients were implanted and 1678 events were recorded in 44 patients. The majority were bradycardias (1461), with 14 episodes of asystole and only one of sustained ventricular tachycardia. Atrial fibrillation, although not defined as clinically significant arrhythmias, was detected in 41% of patients. With thrice-weekly dialysis, the rate was highest during the first dialysis session of the week and was increased during the last 12 hours of each inter-dialytic interval, particularly the long interval. Among serum and dialytic parameters, only higher pre-dialysis serum sodium and dialysate calcium over 2.5 mEq/L were independently associated with clinically significant arrhythmias. Thus, clinically significant arrhythmias are common in hemodialysis patients, and bradycardia and asystole rather than ventricular tachycardia may be key causes of sudden death in hemodialysis patients. Associations with the temporal pattern of dialysis suggest that modification of current dialysis practices could reduce the incidence of sudden death.

Introduction H.P. ACTHar gel is a preparation of melanocortin peptides that has been used to treat resistant forms of nephrotic syndrome. To determine whether combination therapy with ACTHar gel and tacrolimus reduces proteinuria and stabilizes renal function, we conducted a prospective, open-label trial in patients with treatment-resistant membranous glomerulopathy (MGN) and focal segmental glomerulosclerosis (FSGS). Methods Nine patients with treatment-resistant MGN and 13 with treatment-resistant FSGS received subcutaneous ACTHar gel for 6 months. Patients with no response or a partial response to ACTHar gel alone received an additional 6 months of therapy with combination ACTHar gel and oral tacrolimus. The study endpoint was the percentage of patients achieving a complete or partial remission after 6 months of combination therapy. Results Among patients with MGN, treatment with ACTHar gel alone achieved a partial remission in 44% and no response in 56% of patients. No patient achieved a complete response with ACTHar gel therapy alone. An additional 6 months of combination therapy with ACTHar gel and tacrolimus resulted in partial and complete response rates of 25% and 75%, respectively. Among patients with FSGS, ACTHar gel therapy alone resulted in complete and partial response rate of 7.7% and 62.0%. Combination therapy increased complete response rates to 17% and partial responses to 66%. Proteinuria (urinary protein-to-creatinine ratio) was significantly reduced in both patients with MGN and those with FSGS after 6 months of ACTHar gel alone and was further reduced among the patients with MGN with the addition of tacrolimus. There were no significant changes in estimated glomerular filtration rate during the treatment phase or long-term follow-up. Discussion Combination therapy with ACTHar gel and tacrolimus was well tolerated by patients with treatment-resistant MGN and FSGS and significantly reduced proteinuria and improved clinical response rates compared with ACTHar gel alone.

Structural heart disease is highly prevalent in patients with chronic kidney disease requiring dialysis. More than 80% of patients with end-stage renal disease (ESRD) are reported to have cardiovascular disease. This observation has enormous clinical relevance because the leading causes of death for patients with ESRD are of cardiovascular disease etiology, including heart failure, myocardial infarction, and sudden cardiac death. The 2 systems most commonly used to classify the severity of heart failure are the New York Heart Association (NYHA) functional classification and the American Heart Association (AHA)/American College of Cardiology (ACC) staging system. With rare exceptions, patients with ESRD who do not receive renal replacement therapy (RRT) develop signs and symptoms of heart failure, including dyspnea and edema due to inability of the severely diseased kidneys to excrete sodium and water. Thus, by definition, nearly all patients with ESRD develop a symptomatology consistent with heart failure if fluid removal by RRT is delayed. Neither the AHA/ACC heart failure staging nor the NYHA functional classification system identifies the variable symptomatology that patients with ESRD experience depending upon whether evaluation occurs before or after fluid removal by RRT. Consequently, the incidence, severity, and outcomes of heart failure in patients with ESRD are poorly characterized. The 11th Acute Dialysis Quality Initiative has identified this issue as a critical unmet need for the proper evaluation and treatment of heart failure in patients with ESRD. We propose a classification schema based on patient-reported dyspnea assessed both pre- and post-ultrafiltration, in conjunction with echocardiography.

With the wider use of imaging and interventional techniques that require the use of iodinated contrast media in seriously ill patients, many clinical situations occur where patients may be at increased risk for contrast-induced nephropathy (CIN). There is little guidance for clinicians in these areas. The aim of this review is to assess the available literature. Acute renal failure is a common complication following coronary artery bypass surgery, and exposure to contrast medium may increase the risk for this condition, although there is insufficient evidence to make a definitive statement. Evidence is also limited for patients with liver disease: in those undergoing transarterial chemoembolization, cirrhosis may be a risk factor for renal failure. There is some evidence that periprocedural hypotension may be a risk factor for CIN after percutaneous coronary intervention, but no published information was identified on the significance of shock or hypotension in other groups of patients. The published evidence on the risk of CIN in renal transplant recipients is inconsistent. In emergency situations, the course of action is usually dictated by clinical circumstances; the renal status of a patient is likely to be unknown and it is important to ensure adequate volume expansion, especially after the procedure. In all clinical situations that are potentially associated with a high risk for CIN, the decision to administer contrast medium is a matter for clinical judgment, based on the clinical status of the patient and the expected benefits of the investigation or procedure.

Various properties of iodinated contrast media (osmolality, ionic versus nonionic, and viscosity) may contribute to contrast-induced nephropathy (CIN). Therefore, the choice of contrast medium affects the risk for CIN. There is good evidence that low-osmolar contrast media are less nephrotoxic than high-osmolar contrast media in patients at increased risk for CIN who receive intra-arterial iodinated contrast. Current evidence suggests that nonionic isosmolar contrast presents the lowest risk for CIN in patients with chronic kidney disease (CKD), particularly in those patients with diabetes mellitus. Intra-arterial administration of contrast media may be associated with a greater risk for CIN above that observed with intravenous administration. The use of gadolinium or CO 2 as alternative contrast media to avoid the risk of nephrotoxicity cannot be substantiated by clinical trials and therefore cannot be recommended. Most studies show that, within a class, higher volumes (>100 mL) of iodinated contrast medium are associated with a higher risk for CIN. However, in patients at high risk, such as those with CKD and diabetes, even small volumes of contrast medium can have adverse effects on renal function.

In order to make appropriate decisions about clinical management, it is important for physicians to be able to stratify patients according to their risk for contrast-induced nephropathy (CIN). The most important risk marker for nephropathy after exposure to iodinated contrast media is preexisting renal impairment. The risk of CIN is elevated and becomes clinically important in patients with chronic kidney disease characterized by an estimated glomerular filtration rate

Contrast-induced nephropathy (CIN) is the third leading cause of acute kidney injury in hospitalized patients and is associated with significant patient morbidity. The pathogenesis of CIN is complex and not fully understood, but iodinated contrast agents induce intense and prolonged vasoconstriction at the corticomedullary junction of the kidney. Moreover, high-osmolar dyes directly impair the autoregulatory capacity of the kidney through a loss of nitric oxide production. These effects, coupled with direct tubular toxicity of contrast media, lead to overt acute tubular necrosis and the syndrome of CIN.

Background: Acute tubular necrosis (ATN) occurs commonly in critically ill patients and is associated with increased morbidity and mortality. Fenoldopam is a dopamine receptor α1-specific agonist that increases renal blood flow in patients with kidney failure. We hypothesized that administration of low-dose fenoldopam during early ATN would decrease the need for dialysis therapy and/or incidence of death at 21 days. Methods: We conducted a prospective, randomized, double-blind, placebo-controlled, clinical trial in 155 patients with early ATN. Patients were considered eligible for enrollment if serum creatinine level increased to 50% greater than admission levels within 24 hours and mean arterial pressure was greater than 70 mm Hg. Patients were randomly assigned to the administration of placebo or fenoldopam for 72 hours. Results: Overall, 22 of 80 patients (27.5%) in the fenoldopam group reached the primary end point compared with 29 of 75 patients (38.7%) in the placebo group (P = 0.235). This 11% absolute reduction in the primary end point was not statistically significant (P = 0.23). Similarly, there was no difference in the incidence of dialysis therapy between patients randomly assigned to fenoldopam (13 of 80 patients; 16.25%) versus the placebo group (19 of 75 patients; 25.3%; P = 0.163). Moreover, there was no statistically significant difference in 21-day mortality rates between the 2 groups (fenoldopam, 13.8% versus placebo, 25.3%; P = 0.068). In secondary analyses, fenoldopam tended to reduce the primary end point in patients without diabetes and postoperative cardiothoracic surgery patients with early ATN (fenoldopam patients without diabetes, 14 of 54 patients [25.9%] versus placebo patients without diabetes, 23 of 52 patients [44.2%]; P = 0.048) and postoperative cardiothoracic patients (6 of 34 patients [17.6%] versus 14 of 36 patients [38.8%]; P = 0.049). Conversely, fenoldopam did not improve the primary end point in patients with diabetes or those with acute renal failure from other causes. A larger multicenter trial using separate randomizations for patients with and without diabetes will be needed to determine the efficacy of fenoldopam mesylate in specific subpopulations with ATN. Conclusion: Fenoldopam does not reduce the incidence of death or dialysis therapy in intensive care unit patients with early ATN.

Background Radiocontrast nephropathy (RCN) is a common source of acute renal failure in hospitalized patients and is associated with increased morbidity and mortality rates. Fenoldopam mesylate is a dopamine A1 receptor agonist that augments renal plasma flow (RPF) in patients with normotensive and hypertensive conditions. To determine whether fenoldopam mesylate attenuates reductions in RPF after contrast infusion, we conducted a double-blind, randomized, placebo-controlled pilot trial of fenoldopam mesylate in patients who underwent contrast angiography. Methods Fifty-one patients with chronic renal insufficiency (creatinine level, 2.0-5.0 mg/dL) who were undergoing contrast angiography were screened, and 45 patients were randomized to receive normal saline solution (1/2 NS) or 1/2 NS plus fenoldopam mesylate at 0.1 μg/kg/min at lease 1 hour before infusion with contrast dye. Serum creatinine level was measured at baseline and at 24, 48, and 72 hours after angiography. The primary endpoint was change in RPF 1 hour after contrast infusion. The secondary endpoint was incidence of RCN, defined as a 0.5 mg/dL or a 25% rise in serum creatinine level at 48 hours. Results RPF at 1 hour after angiography was 15.8% above baseline in the fenoldopam mesylate group compared with 33.2% below baseline in the 1/2 NS group (P

Nephron segment-specific inhibition of Na+/K+-ATPase activity by cyclosporin A. Decreased kaliuresis and hyperkalemia are common complications of cyclosporin A (CsA) therapy. If CsA significantly inhibits renal tubular Na+/K+-ATPase activity, the alteration in transepithelial K+ secretion and K+ homeostasis could result in hyperkalemia. To investigate this possibility, we tested the effects of CsA on Na+/K+-ATPase activity in microdissected rat tubules. CsA, at a “toxic” concentration of 600 ng/ml, significantly inhibited Na+/K+-ATPase in cortical collecting ducts (CCD), medullary thick ascending limbs (mTAL), and outer medullary collecting ducts from the outer stripe (OMCDos) by 35%, 53%, and 39%, respectively. Cremophore, the commercial vehicle for CsA, did not change Na+/K+-ATPase activity in any nephron segment tested. To determine whether CsA inhibits Na+/K+-ATPase activity in a dose-dependent manner, microdissected CCD's were incubated with 300, 600, and 2500 ng/ml of CsA for 30 minutes. Na+/K+-ATPase activity was inhibited at 600 and 2500 ng/ml, but not at 300 ng/ml. No further inhibition of enzyme activity was noted at 2500 ng/ml. CsA did not change Na+/K+-ATPase activity in proximal tubule S1, S2, and S3 subsegments; cortical thick ascending limbs (cTAL), connecting tubules (CNT), or outer medullary collecting ducts from the inner stripe (OMCDis). Prolonging the incubation of CsA with S2 subsegments to 60 minutes did not result in inhibition of Na+/K+-ATPase activity. Ouabain-insensitive ATPase activity was unaffected by CsA or its vehicle in any nephron segment tested. In summary, CsA specifically inhibits Na+/K+-ATPase activity in the CCD, mTAL, and OMCDos. In the CCD, inhibition of Na+/K+-ATPase activity was dose-dependent and occurred at concentrations commonly associated with clinical CsA toxicity (600 to 2500 ng/ml). CsA-induced inhibition of Na+/K+-ATPase activity in the CCD and OMCDos could decrease K+ secretion and contribute to clinical hyperkalemia.

The authors present a patient who experienced cocaine-related thrombotic microangiopathy and patchy renal cortical necrosis, associated with the clinical syndrome of microangiopathic hemolytic anemia, thrombocytopenia and acute renal failure, characteristics of the Hemolytic-Uremic syndrome. The proposed pathogenetic mechanisms include: (1) cocaine-induced vasoconstriction and endothelial damage and (2) procoagulant effects of cocaine.

Study objective Recent studies have demonstrated that a single episode of acute kidney injury from a number of causes can increase the risk of severe long-term outcomes, including major cardiovascular events and death. We tested the hypothesis that patients who develop acute kidney injury consistent with contrast-induced nephropathy after contrast-enhanced computed tomography (CT) imaging are at increased risk of major adverse events at 1 year. Methods We followed a prospective, heterogeneous cohort of consecutive emergency department patients undergoing contrast-enhanced CT for the outcomes of acute kidney injury consistent with contrast-induced nephropathy and major adverse events, defined as the combined outcome of death (all cause), renal failure, myocardial infarction, and stroke or other arterial vascular events, in any anatomic territory, requiring invention within 1 year. The primary outcome, major adverse events, was determined by the consensus of 2 of 3 blinded adjudicators. Results We followed 633 patients undergoing contrast-enhanced CT, of whom 11% developed acute kidney injury consistent with contrast-induced nephropathy and 15% (95/633; 95% confidence interval [CI] 12% to 18%) experienced at least 1 major adverse event within 1 year, including 7% (46/633; 95% CI 5% to 9%) who died. The development of acute kidney injury after contrast-enhanced CT was associated with an increased risk of 1-year major adverse event: the incident risk ratio was 4.01 (95% CI 2.61 to 6.05) and was 2.36 (95% CI 1.49 to 3.75) after adjusting for age, existing coronary artery disease, active malignancy, and 1 or more additional exposures to intravascular iodinated contrast media. Conclusion The development of acute kidney injury after contrast-enhanced CT was associated with a 2-fold increase in 1-year major adverse events. Further research is needed to validate this observation.

Abnormal calcium metabolism is a common complication of rhabdomyolysis -induced acute renal failure. During the oliguric phase, patients are frequently hypocalcemic. Hyperphosphatemia and skeletal resistance to parathyroid hormone are believed to be possible underlying mechanisms. In addition, there have been reports of hypercalcemia during the diuretic recovery phase after rhabdomyolysis. The pathophysiology of the hypercalcemia observed in the recovery phase is a subject of debate. Several mechanisms have been proposed, including mobilization of calcium from muscle deposits, secondary hyperparathyroidism, and elevated levels of 1,25 dihydroxyvitamin D. The authors report the case of a 30-year-old man admitted for evaluation of marked hypercalcemia (18.3 mg/dL) who was hospitalized 3 weeks earlier for acute renal failure secondary to rhabdomyolysis. Plasma parathyroid hormone and 1,25 dihydroxyvitamin D levels were suppressed during the period of maximal hypercalcemia. A technetium pyrophosphate scan demonstrated extensive deposition of calcium throughout the pelvic and lower extremity muscles. This case of delayed hypercalcemia after rhabdomyolysis supports the hypothesis that mobilization of calcium deposits from soft tissue, including muscle, is central to the pathogenesis of this syndrome.