Association of Serum Free Light Chain Level with Long-Term Kidney Function in Patients with Newly Diagnosed Multiple Myeloma.

INTRODUCTION: Multiple myeloma (MM) frequently involves the kidneys, resulting in acute, subacute, or chronic kidney disease (CKD). Patient- and treatment-related factors are associated with the long-term development of CKD. The aim of our study was to examine the association of serum free light chain (FLC) levels, measured at the time of diagnosis of MM, and CKD at subsequent follow-up. METHODS: Patients with newly diagnosed MM were identified using cancer registries at five hospitals. The primary outcome was low eGFR (<60 mL/min/1.73 m2) or dialysis dependence and a secondary composite outcome of low eGFR, dialysis dependence, or death at the last follow-up, up to 12 months from diagnosis. Logistic regression analyses were performed. RESULTS: A total of 149 patients met the inclusion criteria. Patients with an FLC level above the median had a higher frequency of hypertension (54% vs. 81%; p < 0.001), hyperlipidemia (37% vs. 56%; p = 0.018), low eGFR at the time of diagnosis (43% vs. 66%; p = 0.006), and a higher MM stage (p = 0.018). On multivariable analyses, after adjustment for several covariates, serum FLC level (per each 100 mg/L) was independently associated with low eGFR or dialysis dependence at follow-up (adjusted odds ratio [aOR] 1.021; 95% CI: 1.002, 1.041; p = 0.033). This association persisted for the composite outcome of low eGFR, dialysis dependence, or death (aOR 1.034; 95% CI: 1.006, 1.063; p = 0.018). DISCUSSION/CONCLUSION: Higher serum FLC level measured at the time of MM diagnosis is independently associated with CKD at up to 12 months of follow-up.

Implementation of a palliative care consultation trigger tool for hospitalised patients with acute decompensated heart failure.

Heart failure is a leading cause of hospitalisations. Integration of palliative care services with medical therapy in the management of hospitalised patients with heart failure is imperative. Unfortunately, there are no standardised criteria for palliative care referrals among hospitalised patients with acute decompensated heart failure. The objective of our quality improvement project was to develop and implement a palliative care consult trigger tool for hospitalised patients with acute decompensated heart failure. We found that among eligible patients, palliative care referrals were underused, likely contributing to misalignment of goals of care and suboptimal advance care planning. We developed a trigger tool and designed and implemented structured multicomponent educational interventions to improve the appropriateness and timeliness of inpatient palliative care consultations in this high-risk population. The educational interventions led to a significant increase in the rate of appropriate inpatient palliative care consultations among hospitalised patients with acute decompensated heart failure (46.3% vs 27.7%; p=0.02). In addition, palliative care referrals resulted in better alignment of goals of care at the time of hospital discharge, as measured by a significant increase in the completion rate of a healthcare proxy form (11.4% vs 47.2%; p<0.001) and a Medical Order for Life-Sustaining Treatment form (2.0% vs 24.1%; p<0.001), as well as the establishment of a Do-Not-Resuscitate order (2.7% vs 29.6%; p<0.001). Furthermore, the intervention resulted in a significant decrease in the hospital readmission rate up to 90 days post-discharge (43.6% vs 8.3%; p<0.001). This quality improvement project calls for the development and adoption of standardised criteria for palliative care referrals to benefit hospitalised patients with heart failure and reduce symptom burden, align goals of care and improve quality of life.

Acute on chronic bilateral renal vein thrombosis in the setting of remission of class V lupus nephritis: A case report and literature review.

Renal vein thrombosis (RVT), defined as the presence of a thrombus in the major renal vein or one of its tributaries, can present acutely or go unnoticed resulting in acute kidney injury or chronic kidney disease. RVT is associated with multiple etiologies, including nephrotic syndrome, thrombophilia, autoimmune disorders, and malignancy. Patients with systemic lupus erythematosus (SLE), a multiorgan autoimmune disorder, are predisposed to coagulopathy and thus are at a higher risk of venous and arterial thromboembolism. We describe the case of a 41-year-old man with SLE and biopsy-proven membranous glomerulonephritis (WHO class V lupus nephritis) in clinical remission with no evidence of nephrotic range proteinuria who presented with macroscopic hematuria and was diagnosed with acute-on-chronic bilateral RVT. We discuss the different causes of RVT and compare the clinical presentation, diagnostic imaging findings, and management of acute and chronic RVT.

Cerebral venous thrombosis in an adult with relapsing minimal change disease.

Minimal change disease (MCD) is a well-known cause of fulminant acute nephrotic syndrome (NS) and has been associated with thrombotic complications. We report the case of a 51-year-old woman with previous biopsy-proven MCD in remission who presented with worsening headache and acute confusion shortly after a relapse of the NS and was diagnosed with cerebral venous thrombosis (CVT) complicated by intracranial hemorrhage and midline shift. One month prior, she had been initiated on an oral contraceptive agent during remission of the NS. After initiation of systemic anticoagulation, her condition rapidly deteriorated, and she passed away before being able to undergo catheter-based venous thrombectomy. We conducted a systematic literature review and identified 33 case reports of adults with NS-associated CVT. The most common symptoms were headache (83%), nausea or vomiting (47%), and altered mental status (30%). 64% of patients presented at time of initial diagnosis of the NS and 32% during a relapse. Mean urinary protein excretion was 9.32 g/day and mean serum albumin was 1.8 g/dL. 91% of patients received systemic anticoagulation, and 19% died. The outcome in the remaining cases was favorable with only one report (5%) of residual neurological deficit. Of the available kidney biopsy results, MCD was the most common diagnosis (70%), raising the hypothesis that the fulminant acute onset of the NS might be a predisposing factor for this serious thrombotic complication. Clinicians should have a high index of suspicion for CVT in patients with the NS who present with new-onset neurological symptoms, including headache and nausea.

Recent Trends in Infective Endocarditis Among Patients with and Without Injection Drug Use: An Eight-Year Single Center Study.

BACKGROUND: Infective endocarditis (IE) is associated with considerable morbidity and mortality. Given the opioid crisis and emergence of drug-resistant organisms, we sought to examine annual trends in hospitalization rates for IE and potential epidemiologic shift in the causative microorganisms among patients with and without injection drug use (IDU). METHODS: This was a single-center retrospective cohort study of hospitalized adults with IE. Annual trends in hospitalization rates were calculated (2011-2018), and patient characteristics and clinical outcomes were compared according to IDU status. RESULTS: Our cohort of 244 hospitalized patients with IE had a subset of 112 with IDU. The annual hospitalization rate for IE increased almost four-fold and was most notable among patients with IDU. The highest increase occurred in patients with Staphylococcus aureus-associated IE. Patients with IDU were younger, and more likely to be women with tricuspid valve vegetations and have IE due to methicillin-sensitive and methicillin-resistant Staphylococcus aureus. Patients without IDU were more likely to have central venous catheters with mitral and aortic valve vegetations and have IE due to Streptococcus and coagulase-negative Staphylococcus species. Patients without IDU had a higher requirement for cardiac surgery and higher 90-day mortality. Age was the only independent variable associated with 90-day mortality. CONCLUSIONS: The rising incidence of IE in younger and older persons is driven in part by the opioid public health crisis and higher prevalence of indwelling central venous catheters, respectively. Timely treatment of opioid use disorders and stewardship surrounding use of central venous catheters is urgently needed.

Malignancy-induced lactic acidosis in adult lymphoma.

Malignancy-induced lactic acidosis (MILA), a rare paraneoplastic phenomenon, is mostly described with hematologic malignancies (lymphomas and leukemias) but has also been reported with solid tumors. It is a subset of type B lactic acidosis being mediated without evidence of tissue hypoperfusion. Lymphoma-induced lactic acidosis is often considered an oncologic emergency and is associated with an increased risk of mortality and poor prognosis. It has a complex pathophysiology centered in the "Warburg effect," i.e., the programming of cancer cells to depend on aerobic glycolysis for promotion of their proliferation and anabolic growth. The treatment of lymphoma-induced lactic acidosis is focused on prompt administration of chemotherapy. The role of alkali therapy in this setting is controversial and has limited proven benefit with a potential for worsening the lactic acidosis. If alkali therapy is used in the presence of severe acidemia to optimize cardiovascular status, it should be administered judiciously.

Secondary Oxalate Nephropathy: A Systematic Review.

INTRODUCTION: Little is known of the clinical outcomes of secondary oxalate nephropathy. To inform clinical practice, we performed a systematic review of case reports and case series to examine the clinical characteristics and outcomes of patients with secondary oxalate nephropathy. METHODS: Electronic databases were searched for case reports and case series of individual cases or cohorts of patients with biopsy-proven oxalate nephropathy in native or transplanted kidneys from 1950 until January 2018. RESULTS: Fifty-seven case reports and 10 case series met the inclusion criteria, totaling 108 patients. The case series were meta-analyzed. Mean age was 56.4 years old, 59% were men, and 15% were kidney transplant recipients. Fat malabsorption (88%) was the most commonly attributed cause of oxalate nephropathy, followed by excessive dietary oxalate consumption (20%). The mean baseline serum creatinine was 1.3 mg/dl and peaked at 4.6 mg/dl. Proteinuria, hematuria, and urinary crystals was reported in 69%, 32%, and 26% of patients, respectively. Mean 24-hour urinary oxalate excretion was 85.4 mg/d. In addition to universal oxalate crystal deposition in tubules and/or interstitium, kidney biopsy findings included acute tubular injury (71%), tubular damage and atrophy (69%), and interstitial mononuclear cell infiltration (72%); 55% of patients required dialysis. None had complete recovery, 42% had partial recovery, and 58% remained dialysis-dependent. Thirty-three percent of patients died. CONCLUSION: Secondary oxalate nephropathy is a rare but potentially devastating condition. Renal replacement therapy is required in >50% of patients, and most patients remain dialysis-dependent. Studies are needed for effective preventive and treatment strategies in high-risk patients with hyperoxaluria-enabling conditions.

Plasmapheresis for treatment of immune complex-mediated glomerulonephritis in infective endocarditis: a case report and literature review.

We report the case of a 57-year-old man who presented with subacute bacterial endocarditis secondary to Streptococcus mutans complicated by biopsy-proven immune complex-mediated glomerulonephritis (ICGN). Despite initial treatment with antibiotics and a short course of corticosteroids, the kidney function further deteriorated, and plasmapheresis was introduced as third-line therapy to remove circulating immune complexes. Following 7 treatment sessions, the patient recovered kidney function. We discuss the potential merit of plasmapheresis for patients with subacute bacterial endocarditis who develop ICGN.

Association of Preoperative Urinary Uromodulin with AKI after Cardiac Surgery.

BACKGROUND AND OBJECTIVES: AKI is a serious complication after cardiac surgery. Although high urinary concentrations of the tubular protein uromodulin, a marker of tubular health, are associated with less AKI in animal models, its relationship in humans is unknown. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: A post hoc analysis of a prospective cohort study of 218 adults undergoing on-pump cardiac surgery between 2004 and 2011 was conducted. Multivariable logistic and linear regression analyses were used to evaluate the associations of preoperative urinary uromodulin-to-creatinine ratio with postoperative AKI (defined as a rise in serum creatinine of >0.3 mg/dl or >1.5 times baseline); severe AKI (doubling of creatinine or need for dialysis) and peak postoperative serum creatinine over the first 72 hours. RESULTS: Mean age was 68 years, 27% were women, 95% were white, and the median uromodulin-to-creatinine ratio was 10.0 µg/g. AKI developed in 64 (29%) patients. Lower urinary uromodulin-to-creatinine ratio was associated with higher odds for AKI (odds ratio, 1.49 per 1-SD lower uromodulin; 95% confidence interval, 1.04 to 2.13), which was marginally attenuated after multivariable adjustment (odds ratio, 1.43; 95% confidence interval, 0.99 to 2.07). The lowest uromodulin-to-creatinine ratio quartile was also associated with higher odds for AKI relative to the highest quartile (odds ratio, 2.94; 95% confidence interval, 1.19 to 7.26), which was slightly attenuated after multivariable adjustment (odds ratio, 2.43; 95% confidence interval, 0.91 to 6.48). A uromodulin-to-creatinine ratio below the median was associated with higher adjusted odds for severe AKI, although this did not reach statistical significance (odds ratio, 4.03; 95% confidence interval, 0.87 to 18.70). Each 1-SD lower uromodulin-to-creatinine ratio was associated with a higher adjusted mean peak serum creatinine (0.07 mg/dl per SD; 95% confidence interval, 0.02 to 0.13). CONCLUSIONS: Lower uromodulin-to-creatinine ratio is associated with higher odds of AKI and higher peak serum creatinine after cardiac surgery. Additional studies are needed to confirm these preliminary results.

We Use Impure Water to Make Dialysate for Hemodialysis.

Patients receiving hemodialysis are exposed to a large volume of water, used to prepare dialysate for each treatment session. Technological advancements now make it possible to generate ultrapure dialysate that has substantially lower bacterial and endotoxin counts than the standard dialysate used in the United States. Low-level water contamination is thought to propagate a state of chronic inflammation seen in hemodialysis patients, and a number of studies demonstrate that the use of ultrapure dialysate has a favorable effect on laboratory parameters of inflammation, nutrition, erythropoietin responsiveness, dialysis-associated amyloidosis, and atherosclerosis. Few studies even suggest a direct clinical benefit of adopting ultrapure dialysate. As there is no proven harm with use of ultrapure dialysate and the economic implication appears to be minimal when using modern dialysis machines, it is imperative for regulatory agencies and the dialysis community to ensure that our vulnerable patients are no longer exposed to impure water during their hemodialysis treatments.

Pauci-immune crescentic glomerulonephritis associated with use of trimethoprim-sulfamethoxazole.

Drug-induced pauci-immune crescentic glomerulonephritis has been described with several agents, including propylthiouracil, minocycline, D-penicillamine, and hydralazine. We present the case of a 60-year-old man who presented with rapidly progressive glomerulonephritis in the setting of recent use of trimethoprim-sulfamethoxazole complicated by the development of the Stevens-Johnson syndrome, and was found to have biopsy-proven pauci-immune crescentic glomerulonephritis and undetectable anti-neutrophilic cytoplasmic antibodies. We review the existing literature on the potential association between sulfonamides and hypersensitivity polyangiitis.

Common Iliac Artery Thrombosis following Pelvic Surgery Resulting in Kidney Allograft Failure Successfully Treated by Percutaneous Transluminal Angioplasty with Balloon-Expandable Covered Stent.

We report the case of a 66-year-old woman who developed acute kidney allograft failure due to thrombotic occlusion of the common iliac artery after hysterectomy requiring emergent allograft rescue. She underwent percutaneous transluminal angioplasty with endovascular balloon expandable covered stent graft placement in the right common iliac artery. Although there are a handful of case reports of acute limb ischemia secondary to acute common iliac artery thrombosis, this is the first case reported in the literature resulting in successful kidney allograft rescue following pelvic surgery.

Community- and healthcare-associated infections in critically ill patients: a multicenter cohort study.

OBJECTIVE: To compare the spectrum of infection, comorbidities, outcomes, and mortality of patients admitted to the intensive care unit (ICU) due to community-acquired or healthcare-associated severe sepsis. METHODS: This prospective cohort study was conducted in three university medical centers in Lebanon from February 2005 to December 2006. Patients with severe sepsis were included and followed up until hospital discharge or death. RESULTS: One hundred and twenty patients were included of whom 60% had community-acquired infections (CAI) and 40% had healthcare-associated infections (HAI). The most common infection in both groups was pneumonia. Hematologic malignancies were the only comorbidity more prevalent in HAI than in CAI (p=0.047). Fungal infections and extended-spectrum beta-lactamase (ESBL) organisms were more frequent in HAI than in CAI (p=0.04 and 0.029, respectively). APACHE and SOFA scores were high and did not differ between the two groups, nor did the proportion of septic shock, while mortality was significantly higher in the HAI patients than in the CAI patients (p=0.004). On multivariate analysis for mortality, independent risk factors were the source of infection acquisition (p=0.004), APACHE II score (p=0.006), multidrug-resistant Pseudomonas infections (p=0.043), and fungal infections (p=0.006). CONCLUSIONS: Severe sepsis and septic shock had a high mortality rate, especially in the HAI group. Patients with risk factors for increased mortality should be monitored and aggressive treatment should be administered.

Potential association between membranous nephropathy and sargramostim therapy for pulmonary alveolar proteinosis.

We present the case of a 43-year-old woman with a diagnosis of pulmonary alveolar proteinosis, on chronic treatment with sargramostim, a recombinant granulocyte-macrophage colony-stimulating factor, who presented with the nephrotic syndrome secondary to biopsy-proven membranous nephropathy. We discuss potential underlying mechanisms, including speculated effects of sargramostim on mesangial cells and the kidney resident macrophages, and review the existing literature on the potential association between these two disorders.

Efficacy and safety of intravenous iron therapy for functional iron deficiency anemia in hemodialysis patients: a meta-analysis.

BACKGROUND: Studies on benefits of intravenous iron therapy among hemodialysis patients with functional iron deficiency anemia have shown conflicting results. We conducted a meta-analysis to assess the efficacy and safety of intravenous iron in this subset of patients. METHODS: We searched MEDLINE (through December 2012), the Cochrane Central Register of Controlled Trials and ClinicalTrials.gov for single-arm studies and randomized controlled trials (RCT) that examined the effect of intravenous iron for functional iron deficiency anemia in hemodialysis patients on anemia parameters and markers of oxidative stress and inflammation. Studies of absolute iron deficiency were excluded. Random-effect model meta-analyses were used to compute changes in outcomes of interest. RESULTS: We identified 34 studies (2,658 patients), representing 24 single-arm studies, and 10 parallel-arm RCT. In the analyses of the study arms, intravenous iron therapy resulted in a significant increase in hemoglobin, serum ferritin, transferrin saturation rate, serum iron, reticulocyte hemoglobin content as well as a significant decrease in the percentage of hypochromic erythrocytes and erythropoietin dose. There were significant increases in plasma malonyldialdehyde level and thiobarbituric acid-reactive substances, and a decrease in neutrophil respiratory burst. The analyses of the RCT revealed less robust net changes in these parameters, and there was no increased risk of adverse events including infections, cardiac events and mortality. CONCLUSIONS: Intravenous iron therapy for functional iron deficiency anemia in hemodialysis patients improves anemia parameters but exerts some effects on markers of oxidative stress that are of unclear clinical significance. The long-term safety and efficacy of this treatment strategy requires further study.

Acute oxalate nephropathy associated with Clostridium difficile colitis.

We report the case of a 69-year-old man who presented with acute kidney injury in the setting of community-acquired Clostridium difficile-associated diarrhea and biopsy-proven acute oxalate nephropathy. We discuss potential mechanisms, including increased colonic permeability to oxalate. We conclude that C difficile-associated diarrhea is a potential cause of acute oxalate nephropathy.

Tumor necrosis factor alpha promoter polymorphism and severity of acute kidney injury.

BACKGROUND: Tumor necrosis factor-alpha is a proinflammatory cytokine that has been implicated in the pathobiology of acute kidney injury (AKI). METHODS: We explored the association of a functional polymorphism in the promoter region (rs1800629) of the TNFA gene with severity of AKI, as defined by level of glomerular filtration (serum cystatin C and creatinine) and tubular injury (urinary NAG, KIM-1, α-GST, and π-GST) markers, in 262 hospitalized adults. RESULTS: In unadjusted analyses, compared with the GG genotype, the TNFA GA and AA genotype groups tended to have higher enrollment (p = 0.08), peak (p = 0.004), and discharge (p = 0.004) serum creatinine levels, and the AA genotype tended to have a higher enrollment serum cystatin C level (p = 0.04). Compared with the GG genotype, the TNFA GA and AA genotype groups tended to have a higher urinary KIM-1 level (p = 0.03), and the AA genotype group tended to have a higher urinary π-GST level (p = 0.03). After adjustment for sex, race, age, baseline estimated glomerular filtration rate, sepsis, and dialysis requirement, compared with the GG genotype, the TNFA minor A-allele group had a higher peak serum creatinine of 1.03 mg/dl (0.43, 1.63; p = 0.001) and a higher urinary KIM-1 (relative ratio: 1.73; 95% CI: 1.16, 2.59; p = 0.008). The TNFA minor A-allele group also had a higher Multiple Organ Failure score of 0.26 (95% CI: 0.03, 0.49; p = 0.024) after adjustment for sex, race, age, and sepsis. CONCLUSIONS: The TNFA rs1800629 gene polymorphism is associated with markers of kidney disease severity and distant organ dysfunction among patients with AKI. Larger studies are needed to confirm these relationships.

Urinary α- and π-glutathione s-transferases for early detection of acute kidney injury following cardiopulmonary bypass.

CONTEXT: Urinary α-GST and π-GST are renal tubular leakage markers. OBJECTIVE: To evaluate the performance characteristics of these markers for the early detection of acute kidney injury (AKI). MATERIALS AND METHODS: Multicenter prospective cohort study of 252 adults undergoing cardiopulmonary bypass (CPB). RESULTS: AKI developed in 72 patients. The 2 h post-CPB π-GST level modestly predicted the development of AKI, including higher stages of severity, whereas α-GST did not. DISCUSSION: Small number of events and absence of subsequent post-operative biomarker measurements. CONCLUSIONS: Among adults undergoing CPB, urinary π-GST outperformed α-GST for predicting AKI, but neither marker displayed good discrimination.

Dose of erythropoiesis-stimulating agents and adverse outcomes in CKD: a metaregression analysis.

BACKGROUND: Targeting higher hemoglobin levels with erythropoiesis-stimulating agents (ESAs) to treat the anemia of chronic kidney disease (CKD) is associated with increased cardiovascular risk. STUDY DESIGN: Metaregression analysis examining the association of ESA dose with adverse outcomes independent of target or achieved hemoglobin level. SETTING & POPULATION: Patients with anemia of CKD irrespective of dialysis status. SELECTION CRITERIA FOR STUDIES: We searched MEDLINE (inception to August 2010) and bibliographies of published meta-analyses and selected randomized controlled trials assessing the efficacy of ESAs for the treatment of anemia in adults with CKD, with a minimum 3-month duration. Two authors independently screened citations and extracted relevant data. Individual study arms were treated as cohorts and constituted the unit of analysis. PREDICTORS: ESA dose standardized to a weekly epoetin alfa equivalent, and hemoglobin levels. OUTCOMES: All-cause and cardiovascular mortality, cardiovascular events, kidney disease progression, or transfusion requirement. RESULTS: 31 trials (12,956 patients) met the criteria. All-cause mortality was associated with higher (per epoetin alfa-equivalent 10,000-U/wk increment) first-3-month mean ESA dose (incidence rate ratio [IRR], 1.42; 95% CI, 1.10-1.83) and higher total-study-period mean ESA dose (IRR, 1.09; 95% CI, 1.02-1.18). First-3-month ESA dose remained significant after adjusting for first-3-month mean hemoglobin level (IRR, 1.48; 95% CI, 1.02-2.14), as did total-study-period mean ESA dose adjusting for target hemoglobin level (IRR, 1.41; 95% CI, 1.08-1.82). Parameter estimates between ESA dose and cardiovascular mortality were similar in magnitude and direction, but not statistically significant. Higher total-study-period mean ESA dose also was associated with increased rate of hypertension, stroke, and thrombotic events, including dialysis vascular access-related thrombotic events. LIMITATIONS: Use of study-level aggregated data; use of epoetin alfa-equivalent doses; lack of adjustment for confounders. CONCLUSIONS: In patients with CKD, higher ESA dose might be associated with all-cause mortality and cardiovascular complications independent of hemoglobin level.

Recovery of kidney function following delayed use of Theralite™ dialyzer in a patient with myeloma cast nephropathy.

We report the case of a 60- year- old man who presented with newly diagnosed multiple myeloma complicated by biopsy-proven acute cast nephropathy, requiring hemodialysis, plasmapheresis and chemotherapy. After remaining dialysis dependent for 5 weeks, a high cut-off (HCO) dialyzer, intended to use for the removal of plasma substances with a molecular weight of up to 45 kDa such as free light chains, was introduced to his outpatient 4-hour hemodialysis regimen with an increase in treatment frequency to 4 sessions per week. Following 6 weeks of dialysis with the HCO dialyzer, serum levels of free κ light chains declined by more than 75%. Concurrently, he recovered kidney function and discontinued dialysis. He subsequently received a successful autologous stem-cell transplant. We discuss the potential merit of using the HCO dialyzer late in the course of the care of patients with myeloma cast nephropathy who are dialysis dependent.