My Kidney Is Fine, Can't You Cystatin C?

Background: Independent of age, sex, and body composition, individuals of African American race and individuals with high muscle mass have elevated serum creatinine (sCr) levels on average that may result in overestimation of chronic kidney disease (CKD). We present a misdiagnosed case of CKD based on sCr levels, illustrating the utility of cystatin C (CysC) confirmation testing to answer the question: Can confirmation screening of kidney function with CysC in African American patients and patients with high muscle mass reduce the misdiagnosis of CKD? Case Presentation: A 35-year-old African American man with a history of well-controlled HIV was found to have consistently elevated creatinine (Cr). We diagnosed CKD stage 3A based on the estimated glomerular filtration rate (eGFR). Further evaluation showed isolated elevation of sCr with unremarkable urinalysis and other laboratory tests. sCr elevation predated diagnosis and HIV treatment. A CysC-based eGFR (eGFRcys) test confirmed the absence of CKD. Conclusions: The 2009 CKD Epidemiology Collaboration calculation of eGFR based on sCr concentration uses age, sex, and race, with an updated recommendation in 2021 to exclude race. Both equations are less accurate in African American patients, individuals taking medications that interfere with sCr secretion and assay, and patients taking creatine supplements or high protein intake. These clinical scenarios decrease sCr-based eGFR (eGFRCr) but do not change measured eGFR or eGFRCys. Using sCr and serum cystatin C (eGFRCr-Cys) yields better concordance to measured eGFR across all races than does eGFR estimation based on Cr alone. Confirmation with CysC can avoid misdiagnosis, incorrect dosing of drugs, and inaccurate representation of the fitness for duty.

Detection of methaemoglobinaemia in a COVID-19 patient on dapsone.

Methaemoglobinaemia occurs when iron in haemoglobin is oxidised into a form that cannot transport oxygen. At low levels, it is asymptomatic, though at rising levels symptoms arise from impaired oxygenation, and it can ultimately be fatal. While uncommon, it is important to consider in hypoxaemic COVID-19 patients, especially if they are not clinically improving on standard treatments and workup for other causes does not explain the ongoing hypoxaemia. It is often diagnosed through a mismatch in peripheral and arterial oxygen, with the former typically less than the latter. We present the case of a COVID-19 patient who was found to have methaemoglobinaemia due to dapsone use for Pneumocystic jirovecii pneumonia (PJP) prophylaxis while on chemotherapy. Dapsone was stopped and supplemental high-flow nasal cannula was provided, and methaemoglobin levels improved over a 5-day period. She was discharged to follow-up with her haematologist in the clinic.

Goiter and Abdominal Mass: A Rare Presentation of Riedel's Thyroiditis.

Riedel's thyroiditis (RT) is a rare inflammatory autoimmune disease, often associated with various forms of systemic fibrosis such as sclerosing mesenteritis (SM). A woman in her late 30s presented with a diffusely enlarged firm goiter and a mesenteric mass complicated by biliary obstruction and hydronephrosis. Labs and thyroid ultrasound were consistent with autoimmune thyroiditis. Abdominal imaging demonstrated a mesenteric mass that encased mesenteric vessels and ureter. Flow cytometry and infectious workup were negative. Both thyroid and mesenteric biopsies revealed dense fibrosis with patchy lymphoplasmacytic aggregates, no evidence of carcinoma, lymphoma, or IgG4-related disease, which confirmed diagnoses of RT and SM. She improved clinically with steroids. The coincidental timing of thyroid enlargement and the mesenteric mass, and the similarity in histology suggest an association between RT and SM. Overall, the case highlights the challenges in diagnosing RT given its rarity and emphasises the importance of early treatment to prevent systemic involvement.

Prescribing patterns of SGLT-2 inhibitors for patients with heart failure: A two-center analysis.

Background: Sodium glucose co-transporter 2 inhibitors (SGLT2i) have been proven to reduce the combined risk of cardiovascular death and hospitalizations in patients with heart failure (HF), irrespective of the presence or absence of diabetes. Despite class 1 and class 2A recommendations for their usage in HF with reduced ejection fraction (HFrEF) and HF with preserved ejection fraction (HFpEF) respectively by the American College of Cardiology, their prescription rate has remained low. Objective: The aim of this study is to analyze SGLT2i prescription patterns at two academic institutions, with the goal of identifying barriers to implementation. Design: A two-center retrospective analysis was conducted on patients ≥18 years old with a diagnosis of heart failure who were admitted to one of two hospital systems between 5/1/21 and 5/31/22. Patients with an eGFR ≥20 mL/min/1.73m2 and BNP ≥ 100 pg/mL were included. Results: SGLT2i was prescribed in only 19 out of 1081 HFpEF patients (1.8 %) and 51 out of 1596 HFrEF patients (3.2 %). A majority of SGLT2i prescriptions for the HFpEF population came from general medicine services (57.9 %) after obtaining approval from a cardiologist, which was required at our institutions. Adverse effects such as hypoglycemia and urinary tract infections were not significantly associated with SGLT2i use. Conclusions: Despite proven benefits of this class of medications as witnessed in large-scale clinical trials, the implementation of this drug class continues to be low.

Cutaneous Larvae Migrans Treated with a Single Dose of Ivermectin.

Hookworm-related cutaneous larva migrans (HrCLM) is a clinical diagnosis based on a history of exposure to contaminated soil and is associated with a characteristic red serpiginous lesion that migrates within the epidermis. Our patient presented with a red, tortuous migratory rash with localized pruritus on the left plantar foot of 1-month duration. He lacked recent travel history outside the southeastern United States. Upon admission, he presented with peripheral blood eosinophilia, an uncommon feature of HrCLM. A single dose of ivermectin was sufficient for treatment, and symptoms resolved within 3 days. This case highlights the increased incidence of domestically acquired hookworm infections, explores this epidemiological shift, and emphasizes relevant differential diagnoses.

Glucosuria Is Not Always Due to Diabetes.

Further study of the long-term implications and follow-up is needed on SGLT2 mutation, an uncommon cause of glucosuria that mimics the effect of SGLT2 inhibitors, including the possible development of further renal disease, type 2 diabetes mellitus, and cardiovascular disease.

Euglycemic DKA (euDKA) as a presentation of COVID-19.

COVID-19 in the setting of SGLT2 inhibitor use may precipitate euglycemic DKA separate from known acute viral illness and dehydration precipitants. There should be consideration of proactive discontinuation of these medications in these patients.

Not All Pulmonary Nodules in Smokers are Lung Cancer.

Diagnosis of pulmonary nodules requires an in-depth workup, including clinical evaluation, laboratory and pulmonary functions tests, and imaging, which helped to identify in this patient pulmonary rheumatoid arthritis, an important factor in patient mortality.

Circulating endothelial cells as predictor of long-term mortality and adverse cardiovascular outcomes in hemodialysis patients.

Circulating endothelial cells (CEC) are thought to be markers of endothelial injury. We hypothesized that the numbers of CEC may provide a novel means for predicting long-term survival and cardiovascular events in hemodialysis patients. 54 hemodialysis patients underwent enumeration of their CEC number. We retrospectively analyzed their survival and incidence of adverse cardiovascular events. 22 deaths (41%) were noted over the median follow up period of 3.56 years (IQR 1.43-12) and 6 were attributed to cardiovascular deaths (11%) of which 1 (4%) was in the low CEC (CEC<20 cells/ml) and 5 (19%) in the high CEC (CEC≥20 cells/ml) group. High CEC was associated with worse cardiovascular survival (p = 0.05) and adverse cardiac events (p = 0.01). In multivariate analysis, CEC >20 cells/ml was associated with a 4-fold increased risk of adverse cardiac events (OR, 4.16 [95% CI,1.38-12.54],p = 0.01) while all-cause mortality and cardiovascular mortality were not statistically different. In this hemodialysis population, a single measurement of CEC was a strong predictor of long term future adverse cardiovascular events. We propose that CEC may be a novel biomarker for assessing cardiovascular risk in dialysis patients.

COVID-19-Associated Systemic Thromboembolism: A Case Report and Review of the Literature.

INTRODUCTION: Coronavirus disease 2019 (COVID-19) is a pandemic that has affected >188 countries, involved >24 million people, and caused >840,000 deaths. COVID-19, in its severe form, presents as acute respiratory distress syndrome (ARDS), shock, and multiorgan failure. Thrombotic microangiopathy of the lungs and kidneys has been observed in these patients. Elevated D-dimer levels have been observed in people with serious COVID-19 illness, and this could be helpful in guiding treatment with anticoagulation in these patients. OBJECTIVE: To analyze the role of anticoagulation as a treatment modality for COVID-19. METHODS: We present the unique case of a COVID-19 patient who developed sepsis, ARDS, acute kidney injury, and deep-vein thrombosis (DVT), who was deteriorating clinically. She was treated with anticoagulation. RESULTS: There was rapid recovery after treatment with systemic anticoagulation. CONCLUSIONS: Systemic anticoagulation could prove to be essential in the treatment of CO-VID-19. Further studies are required to assess its role in improving long-term morbidity and mortality in these patients.

Tingles, Tetany, and Electrolyte Derangements.

We report a patient who presented with anxiety, hyperventilation, perioral paresthesia, and tingling in the fingers associated with hypomagnesemia, hypocalcemia, and hypokalemia. We discuss the possible mechanistic basis for sequence of events that may have led to this presentation.

Chest Physiotherapy in Acute Muco-obstructive Lung Disease.

Acute mucus plugging is a pulmonary emergency associated with increased mortality and often requires rapid bronchoscopic intervention which may not be readily available in all centers. Furthermore, the role and efficacy of alternate conventional measures such as mechanical percussive therapies are uncertain. Herein, we present a patient who rapidly progressed to respiratory distress; a chest X-ray revealed left lobar atelectasis highly suggestive of acute mucus plugging. In the absence of rapid bronchoscopic intervention, bedside chest percussion was initiated with improvement in clinical status. Our case demonstrates the successful utilization of chest physiotherapy in the resolution of acute mucus plugging in an urgent situation and highlights the need for careful attention to respiratory status in high-risk patients who are also undergoing fluid removal with dialysis therapies.

Natriuretic peptides in acute kidney injury - A sojourn on parallel tracks?

OBJECTIVE: The focus of this review was to elicit the mechanistic logic of the experimental and clinical study designs of natriuretic peptides (NP) in acute kidney injury (AKI) and to understand their respective outcomes. METHODS: Online search of PubMed and manual review of articles. Randomized trials, observational and physiologic studies of NPs and AKI were extracted. Rationale, design and study outcomes were analyzed. RESULTS: In experimental models of AKI, infusion of NP prevented post-ischemic fall in renal blood flow (RBF) or improvement in RBF, GFR, diuresis and natriuresis and demonstrated anti-inflammatory properties. NPs were most effective in the early stages of AKI, also in established phase of AKI but their effectiveness were limited to the time of infusion. Hypotension was a major side-effect. Based on these observations, preliminary clinical studies were performed which demonstrated improved urine output, RBF and GFR and reduced need for dialysis. However, randomized, controlled trials failed to demonstrate improvement in dialysis-free survival in different cohorts and study designs. Although NPs reduced the incidence of AKI in the postoperative period in cardiac surgery, it was not associated with improved long-term survival. In contrast to randomized trials, meta-analysis reported favorable results. CONCLUSIONS: Reasons for the divergence of experimental and clinical outcomes of NPs in AKI are discussed in this review article.

Renin-Angiotensin-Aldosterone System Optimization for Acute Decompensated Heart Failure Patients (ROAD-HF): Rationale and Design.

INTRODUCTION: The long-term benefits of angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin receptor blockers (ARBs) on outcomes in patients with chronic congestive heart failure are well-known, making them one of the most widely prescribed medications. However, the administration of ACEIs/ARBs in acute decompensated heart failure (ADHF) can increase the risk of morbidity and mortality secondary to worsening renal function (WRF). A decrease in estimated glomerular filtration rate (eGFR) during the treatment of ADHF has been associated with an increase in mortality proportional to the degree of WRF. AIM: The aim of our study is to determine whether withholding ACEIs/ARBs during the initial 72 h of admission in patients with ADHF will prevent WRF and allow more effective diuresis. METHODS: Four hundred and thirty patients will be randomized to the intervention (withholding ACEIs/ARBs) or control (continue/start ACEIs/ARBs) arms for 72 h. Primary outcomes include rates of acute kidney injury (AKI), patient global assessment, and change in kinetic eGFR over 72 h, while secondary outcomes include change in weight, fluid balance, change in signs and symptoms of congestion, change in renal function, change in urinary biomarkers (tissue inhibitor of metalloproteinases 2 [TIMP-2] × insulin-like growth factor-binding protein 7 [IGFBP7]), patients experiencing treatment failure, hospital length of stay (LOS), cost analysis, mortality within 30 days, and hospital readmissions over 30 days and 1 year. CONCLUSION: This prospective clinical trial will prove if withholding ACEIs/ARBs will prevent AKI in ADHF. It will help us understand the complex interactions between the heart and kidney, and delineate the best treatment strategy for ADHF. Holding ACEIs/ARBs might help preserve renal function, and decrease hospital LOS, readmission rates, and cost of care in ADHF. REGISTRATION: ClinicalTrials.gov identifier: NCT03695120.

Continuation of Chronic Heart Failure Therapies During Heart Failure Hospitalization - a Review.

Randomized controlled trials have demonstrated the benefits of guideline-directed medical therapy in the outpatient setting for treatment of chronic heart failure. However, the benefits of continuation (or discontinuation) of major chronic heart failure therapies when treating acute heart failure during hospitalization are less clear. Real and anticipated worsening renal function, hyperkalemia and hypotension are the three major reasons for discontinuation of renin-angiotensin-aldosterone system inhibitors during hospitalization, and a failure to resume renin-angiotensin-aldosterone system inhibitors before discharge could worsen cardiovascular outcomes. Available data, mostly observational, shows that continuation or initiation of renin-angiotensin-aldosterone system inhibitors appears efficacious, safe, and well tolerated in majority of acute heart failure patients during hospitalization. Worsening renal function portends poor prognosis only if associated with congestion in acute heart failure, and clinicians should not de-escalate diuretic therapy routinely for worsening renal function.

Static pressures, intra-access blood flow and dynamic Kt/V profiles in the prediction of dialysis access function.

BACKGROUND: Hemodialysis machine-generated circuit pressures and clearance profiles are potential predictors of quality assurances. In our practice, we previously we observed that elevated static access pressures were associated with abnormal Kt/V values, high access recirculation and deviation of the Kt/V profile (Abnormal Kt/V profile) from normally expected values (Normal Kt/V profile). AIM: To hypothesize that static or derived access pressures would correlate with direct intra-access blood flow rates and that clearance (Kt/V) profiles would correlate with measured Kt/V values. METHODS: Static access pressures, real-time adequacy of dialysis and intra-access blood flow were investigated in end stage renal disease patients undergoing hemodialysis. Wilcoxon-Mann-Whitney test, chi-square test or Fisher's exact test was used to investigate differences between the groups; Spearman's rank correlation test to investigate relationships between static pressures, direct intra-access pressures and Kt/V profiles; and multinomial logistic regression models to identify the independent effect of selected variables on Kt/V profiles. Odds ratio were calculated to measure the association between the variables and Kt/V profiles. RESULTS: One hundred and seven patients were included for analysis. There were no significant differences between genders, and types of vascular access between the normal vs. abnormal clearance (Kt/V) profile groups. No significant correlation could be demonstrated between static access pressures and Kt/V profiles, static access pressures and intra-access blood flow, intra-access blood flow and Kt/V profiles, measured Kt/V and Kt/V profiles or recirculation and Kt/V profiles. CONCLUSION: In this study utilizing measured versus estimated data, we could not validate that dialysis machine generated elevated static pressures predict intra-access blood flow disturbances or that abnormal Kt/V profiles predict access recirculation or inadequate dialysis. These parameters, though useful estimates, cannot be accepted as quality assurance for dialysis adequacy or access function without further evidences.

The Role of Uric Acid in Acute Kidney Injury.

Studies have demonstrated the presence of a strong association between serum uric acid (SUA) and acute kidney injury (AKI) consistently across several disease models. Exposure to SUA at different time periods and concentrations has reliably resulted in AKI whether assessed by conventional or novel biomarkers or by kinetic estimated glomerular filtration rate (KeGFR) engineered for non-steady dynamic states. In experimental models, moderate hyperuricemia was associated with an absence of intrarenal crystals, manifestation of tubular injury, macrophage infiltration, and increased expression of inflammatory mediators that were attenuated with uric acid lowering therapy with rasburicase, a recombinant urate oxidase. In a pilot clinical trial, treatment with rasburicase was associated with a decreased incidence of AKI and evidence for less renal structural injury. Lowering SUA also improved KeGFR and estimated glomerular filtration rate in 2 separate studies. SUA has also been linked to diabetic nephropathy, hypertension, cardiovascular disease, chronic kidney disease, metabolic syndrome, and their mechanisms of action share many common traits. In this article, we explore the evidence for the causal role of SUA in AKI using Bradford Hill criteria as a guideline with data integration from related fields.