The Diagnostic Conundrum of Glomerular Crescents With IgA Deposits.

Introduction: Glomerulonephritis (GN) with crescents and IgA deposits in kidney biopsy poses a frequent diagnostic and therapeutic dilemma because of multiple possibilities. Methods: Native kidney biopsies showing glomerular IgA deposition and crescents (excluding lupus nephritis) were identified from our biopsy archives between 2010 and 2021. Detailed clinicopathologic features were assessed. One-year clinical follow-up on a subset of cases was obtained. Results: A total of 285 cases were identified, and these clustered into IgA nephropathy (IgAN, n = 108), Staphylococcus or other infection-associated GN/infection-related GN (SAGN/IRGN, n = 43), and antineutrophil cytoplasmic antibody-associated GN (ANCA-GN, n = 26) based on a constellation of clinicopathologic features, but 101 cases (group X) could not be definitively differentiated. The reasons have been elucidated, most important being atypical combination of clinicopathologic features and lack of definitive evidence of active infection. Follow-up (on 72/101 cases) revealed that clinicians' working diagnosis was IgAN in 43%, SAGN/IRGN in 22%, ANCA-GN in 28%, and others in 7% of the cases, but treatment approach varied from supportive or antibiotics to immunosuppression in each subgroup. Comparing these cases as "received immunosuppression" versus "non-immunosuppression," only 2 features differed, namely C3-dominant staining, and possibility of recent infection (both higher in the no-immunosuppression group) (P < 0.05). Renal loss was higher in the non-immunosuppression subgroup, but not statistically significant (P = 0.11). Conclusion: Diagnostic overlap may remain unresolved in a substantial number of kidney biopsies with glomerular crescents and IgA deposits. A case-by-case approach, appropriate antibiotics if infection is ongoing, and consideration for cautious immunosuppressive treatment for progressive renal dysfunction may be needed for best chance of renal recovery.

Hypertonic Saline Infusion for Hyponatremia: Limitations of the Adrogué-Madias and Other Formulas.

Hypertonic saline infusion is used to correct hyponatremia with severe symptoms. The selection of the volume of infused hypertonic saline ( VInf ) should address prevention of overcorrection or undercorrection. Several formulas computing this VInf have been proposed. The limitations common to these formulas consist of (1) failure to include potential determinants of change in serum sodium concentration ([ Na ]) including exchanges between osmotically active and inactive sodium compartments, changes in hydrogen binding of body water to hydrophilic compounds, and genetic influences and (2) inaccurate estimates of baseline body water entered in any formula and of gains or losses of water, sodium, and potassium during treatment entered in formulas that account for such gains or losses. In addition, computing VInf from the Adrogué-Madias formula by a calculation assuming a linear relation between VInf and increase in [ Na ] is a source of errors because the relation between these two variables was proven to be curvilinear. However, these errors were shown to be negligible by a comparison of estimates of VInf by the Adrogué-Madias formula and by a formula using the same determinants of the change in [ Na ] and the curvilinear relation between this change and VInf . Regardless of the method used to correct hyponatremia, monitoring [ Na ] and changes in external balances of water, sodium, and potassium during treatment remain imperative.

Renovascular Hypertension with Superimposed Aortic Arch Baroreceptor Failure: Case Report and Review of Literature.

BACKGROUND: Atherosclerotic renal artery diseases are among the most common causes of secondary hypertension. Baroreceptors, as carotid and aortic, are important regulatory mechanisms of blood pressure; their disruption can lead to labile blood pressure due to sympathetic overactivity: an entity called neurogenic hypertension. A disease such as aortic dissection can lead to a challenging combined etiology of secondary hypertension. It can affect both or one of the renal arteries leading to a renovascular pathology that can cause hypertension through RAAS activation. Also, surgical repair of the dissected aortic arch can disrupt baroreceptors leading to neurogenic hypertension. Case Report. We report a case of an 83-year-old female patient investigated for recurrent episodes of aphasia. She has a history of hypertension and coronary artery disease. Surgical history is significant for aortic valve replacement complicated by type A aortic dissection requiring surgical repair. Following surgery, the patient developed difficult-to-control and labile blood pressure. Workup included a CT angiogram of the abdominal aorta that showed an infrarenal dominant abdominal aortic aneurysm with juxtarenal aortic dissection; these findings were similar to previous findings. A diagnosis of aortic baroreceptor failure following aortic dissection repair was established, which lead to labile hypertension with superimposed renovascular pathology due to unilateral compromised renal artery blood flow following aortic dissection and thrombosis. CONCLUSIONS: This report highlights the importance of accurate diagnosis of secondary hypertension and its underlying mechanisms, as this has a huge impact on the choice of therapy to avoid undertreatment or overtreatment of hypertension.

Gut microbiome and diet in populations with obesity: Role of the Na+/K+-ATPase transporter signaling in severe COVID-19.

OBJECTIVE: The triad of obesity, a high-protein diet from animal sources, and disturbed gut microbiota have been linked to poor clinical outcomes in patients with COVID-19. In this report, the effect of oxidative stress resulting from the Na+ /K+ -ATPase transporter signaling cascade is explored as a driver of this poor clinical outcome. METHODS: Protein-protein interactions with the SARS-CoV-2 proteome were identified from the interactome data for Na+ /K+ -transporting ATPase subunit α-1 (ATP1A1), epidermal growth factor receptor, and ERB-B2 receptor tyrosine kinase 2, using the curated data from the BioGRID Database of Protein Interactions. Data for the gene expression pattern of inflammatory response were from the Gene Expression Omnibus database for cardiomyocytes post SARS-CoV-2 infection (number GSE151879). RESULTS: The ATP1A1 subunit of the Na+ /K+ -ATPase transporter is targeted by multiple SARS-CoV-2 proteins. Furthermore, receptor proteins associated with inflammatory response, including epidermal growth factor receptor and ERB-B2 receptor tyrosine kinase 2 (which interact with ATP1A1), are also targeted by some SARS-CoV-2 proteins. This heightened interaction likely triggers a cytokine release that increases the severity of the viral infection in individuals with obesity. CONCLUSIONS: The similarities between the effects of SARS-CoV-2 proteins and indoxyl sulphate on the Na+ /K+ -ATPase transporter signaling cascade suggest the possibility of an augmentation of gene changes seen with COVID-19 infection that can result in a hyperinduction of cytokine release in individuals with obesity.

Machine learning approach to predicting albuminuria in persons with type 2 diabetes: An analysis of the LOOK AHEAD Cohort.

Albuminuria and estimated glomerular filtration rate (e-GFR) are early markers of renal disease and cardiovascular outcomes in persons with diabetes. Although body composition has been shown to predict systolic blood pressure, its application in predicting albuminuria is unknown. In this study, we have used machine learning methods to assess the risk of albuminuria in persons with diabetes using body composition and other determinants of metabolic health. This study is a comparative analysis of the different methods to predict albuminuria in persons with diabetes mellitus who are older than 40 years of age, using the LOOK AHEAD study cohort-baseline characteristics. Age, different metrics of body composition, duration of diabetes, hemoglobin A1c, serum creatinine, serum triglycerides, serum cholesterol, serum HDL, serum LDL, maximum exercise capacity, systolic blood pressure, diastolic blood pressure, and the ankle-brachial index are used as predictors of albuminuria. We used Area under the curve (AUC) as a metric to compare the classification results of different algorithms, and we show that AUC for the different models are as follows: Random forest classifier-0.65, gradient boost classifier-0.61, logistic regression-0.66, support vector classifier -0.61, multilayer perceptron -0.67, and stacking classifier-0.62. We used the Random forest model to show that the duration of diabetes, A1C, serum triglycerides, SBP, Maximum exercise Capacity, serum creatinine, subtotal lean mass, DBP, and subtotal fat mass are important features for the classification of albuminuria. In summary, when applied to metabolic imaging (using DXA), machine learning techniques offer unique insights into the risk factors that determine the development of albuminuria in diabetes.

Acute and Chronic Hyponatremia.

Hyponatremia is the most common electrolyte disorder in clinical practice. Catastrophic complications can occur from severe acute hyponatremia and from inappropriate management of acute and chronic hyponatremia. It is essential to define the hypotonic state associated with hyponatremia in order to plan therapy. Understanding cerebral defense mechanisms to hyponatremia are key factors to its manifestations and classification and subsequently to its management. Hypotonic hyponatremia is differentiated on the basis of urine osmolality, urine electrolytes and volume status and its treatment is decided based on chronicity and the presence or absence of central nervous (CNS) symptoms. Proper knowledge of sodium and water homeostasis is essential in individualizing therapeutic plans and avoid iatrogenic complications while managing this disorder.

Viral Nephropathies, Adding SARS-CoV-2 to the List.

Viral infections in the immunocompetent host can cause both acute and chronic kidney disease either as a direct damage to the infected kidney cells or as a consequence of systemic immune responses that impact kidney function. Since identifying these entities in the 1970s and 80s, major breakthroughs in the understanding of the viral mechanisms have occurred. Viruses have evolved mechanisms to hijack signaling pathways of infected cells to evade antiviral immune responses by the host. Over time, the clinical presentations and management of these diseases have evolved along with our in-depth understanding of the various pathophysiological mechanisms causing these conditions. Similarly, both at the cellular and systemic levels, the host has evolved mechanisms to counter viral subversion strategies for mutual survival. Since the start of the current COVID-19 pandemic, numerous cases of acute kidney injury have been reported in the literature with various possible pathophysiological mechanisms. In this review, we summarize lessons learned from prior viral pandemics related to viral mechanisms utilized in the pathogenesis of numerous renal manifestations to attempt to utilize this knowledge in predicting post-COVID-19 kidney disease.

Can charcoal improve outcomes in COVID-19 infections?

COVID-19 infection causes considerable morbidity and mortality, especially to those who are aged, have impaired renal function and are obese. We propose to examine the potential utility of oral activated charcoal with the hypothesis that such treatment would lower absorption of microbiome derived toxins and ameliorate systemic oxidant stress and inflammation.

Relationship between dietary sodium and sugar intake: A cross-sectional study of the National Health and Nutrition Examination Survey 2001-2016.

Dietary sodium intake and cardiovascular outcomes have a reported J-shaped curve relationship. This study analyzes the relationship between dietary sodium and sugar intake as a potential mechanism to explain this association. The authors examined cross-sectional data from the National Health and Nutrition Examination Survey (NHANES) 2001-2016 where dietary sodium, carbohydrate, fat, cholesterol, and sugar intakes were assessed by 24-hour dietary recall and were standardized to a total daily intake of 2000 calories. Sodium intake was categorized into sodium quintiles (SQ) as follows: SQ1(0.06-2.6 g/d); SQ2(2.6-3.0 g/d); SQ3(3.0-3.4 g/d); SQ4(3.4-4.0 g/d); and SQ5(4.0-29.3 g/d). Simple and multivariate linear regression using SQ3 as reference were used to assess associations between daily sodium intake and the other nutrients. Our results showed that among 38 722 participants that met our study criteria, the mean age was 43.6 years (SD 16.8 years) and sex was equally distributed (48.8% male vs 51.2% female). Sugar intake went down across increasing SQs and was significantly higher in SQ1 (141.2 g/d) and SQ2 (118.6 g/d) and significantly lower in SQ4 (97.9 g/d) and SQ5 (85.6 g/d) compared to SQ3 (108.6 g/d; all P < .01). These same trends remained unchanged and significant in the fully adjusted multivariate model. In conclusion, NHANES study participants reporting low sodium intake on 24-hour dietary recall have a higher consumption of sugar. The negative impact of low sodium diet on cardiovascular health may be explained at least partially by the associated high sugar intake.

A case of gabapentin overdose induced rhabdomyolysis requiring renal replacement therapy.

We report a rare case with gabapentin overdose that caused severe rhabdomyolysis and acute tubular necrosis which required renal replacement therapy. A better awareness of its adverse effect and a close follow-up of laboratory tests are recommended. Prescribers should also be aware of high-risk population and monitor for signs of abuse.

Ammonia vs. Lactic Acid in Predicting Positivity of Microbial Culture in Sepsis: The ALPS Pilot Study.

OBJECTIVE: The use of serum ammonia as a novel marker for sepsis compared to lactic acid levels in intensive care unit (ICU) patients. DESIGN AND INTERVENTIONS: Single arm, prospective clinical trial to collect arterial blood samples from patients with sepsis. Serial ammonia and lactic acid levels were sent every six hours for a total of three days. MEASUREMENTS AND RESULTS: Compare mean levels of ammonia and lactic acid in terms of diagnosing sepsis and patient outcome, including length of stay and mortality. A total of 30 patients were enrolled in the pilot study. On admission, mean ammonia level was 35.7 µmol/L and lactic acid was 3.06 mmole/L. Ammonia levels checked at the end of day 2 (ammonia 2-4) and the beginning of day 3 (ammonia 3-1) were higher in patients who had a microbial culture-proven sepsis (p-values 0.029 and 0.002, respectively) compared to those without culture-positive sepsis. Ammonia levels did predict a longer hospital stay; ammonia level of more than 40 µmol/L had a mean hospital stay of 17.6 days vs. patients with normal levels who had a mean hospital stay of 9.62 days (p-value 0.0082). CONCLUSION: Elevated ammonia level can be a novel biomarker for sepsis, comparable to conventional markers. Ammonia levels have a prognostic utility as elevated levels were associated with longer hospital stay.