Dimensions of muddy brown granular casts in patients with acute tubular injury.

BACKGROUND: The presence of "muddy" brown granular casts (MBGC) in the urine sediment is pathognomonic for acute tubular injury (ATI). Although MBGC have been noted for years, there are no reports regarding their length nor width. The objective of this study was to measure MBGC using images obtained by light microscopy and investigate associations with clinically relevant parameters. METHODS: Patients with diagnosis of ATI as evidenced by visualization of abundant MBGC (>30% low power fields) were sampled. Bright-field images were measured using ImageJ. Twenty-five patients were included: 44% women; median age 64 yrs; 52% white, 36% black. Mean MBGC width (n = 350) was 34.4 ± 13.1 µm (range: 9 to 110 µm). RESULTS: Mean MBGC length was 98.7 ± 42.7 µm (range: 33 to 317 µm). Based on a previous report of cortical tubular diameters, MBGC width corresponded well with the median reported range. MBGC width was positively correlated with patient height (ρ=0.41, p=0.04), and length was positively correlated with fractional excretion of sodium (ρ=0.57. p=0.02) and urine chloride concentration (ρ=0.90, p=0.001). Mean MBGC length was negatively correlated with age (ρ=-0.47, p=0.02) and urine phosphate concentration (ρ=-0.72, p=0.03). There were no differences between cases that required renal replacement therapy (RRT, n =10) and those that did not require RRT (n=15). CONCLUSION: This is the first study reporting dimensions of MBGC from cases with ATI. Clinical implications of these observations require further study.

Cardiovascular, Kidney Failure, and All-Cause Mortality Events in Patients with Focal Segmental Glomerulosclerosis in a U.S. Real-World Database.

BACKGROUND: Focal segmental glomerulosclerosis (FSGS) leads to proteinuria and progressive decline in glomerular filtration rate which correlates with kidney failure and increased cardiovascular risk. The purpose of this study was to estimate the effects of proteinuria on kidney failure status/all-cause mortality and cardiovascular disease events/all-cause mortality, as well as the relationship between progression to kidney failure and occurrence of cardiovascular disease/mortality events among adult patients (≥18 years old) with FSGS. METHODS: This was an observational, retrospective cohort study utilizing Optum® de-identified Market Clarity Data and proprietary Natural Language Processing (NLP) data. The study period was from January 1, 2007 through March 31, 2021, with patients in the overall cohort being identified from July 1, 2007 through March 31, 2021. The index date was the first FSGS ICD-10 diagnosis code or FSGS-related NLP term within the identification period. RESULTS: Elevated proteinuria >1.5 g/g and ≥3.5 g/g increased risk for kidney failure/all-cause mortality (adjusted hazard ratio [95% CI]: 2.34 [1.99-2.74] and 2.44 [2.09-2.84], respectively) and cardiovascular disease/all-cause mortality (adjusted hazard ratio [95% CI]: 2.11 [1.38-3.22] and 2.27 [1.44-3.58], respectively). Progression to kidney failure was also associated with a higher risk of cardiovascular disease/all-cause mortality (adjusted hazard ratio [95% CI]: 3.04 [2.66-3.48]. CONCLUSIONS: A significant proportion of FSGS patients experience kidney failure and cardiovascular disease events. Elevated proteinuria and progression to kidney failure were associated with a higher risk of cardiovascular disease/all-cause mortality events, and, elevated pre-kidney failure proteinuria was associated with progression to kidney failure/all-cause mortality events. Treatments that meaningfully reduce proteinuria and slow the decline in glomerular filtration rate have the potential to reduce the risk of cardiovascular disease, kidney failure and early mortality in patients with FSGS.

Pathophysiology of Hepatorenal Syndrome.

Hepatorenal syndrome type 1 (HRS-1) is a unique form of acute kidney injury that affects individuals with decompensated cirrhosis with ascites. The primary mechanism leading to reduction of kidney function in HRS-1 is hemodynamic in nature. Cumulative evidence points to a cascade of events that led to a profound reduction in kidney perfusion. A state of increased intrahepatic vascular resistance characteristic of advanced cirrhosis and portal hypertension is accompanied by maladaptive peripheral arterial vasodilation and reduction in systemic vascular resistance and mean arterial pressure. As a result of a fall in effective arterial blood volume, there is a compensatory activation of the sympathetic nervous system and the renin-angiotensin system, local renal vasoconstriction, loss of renal autoregulation, decrease in renal blood flow, and ultimately a fall in glomerular filtration rate. Systemic release of nitric oxide stimulated by the fibrotic liver, bacterial translocation, and inflammation constitute key components of the pathogenesis. While angiotensin II and noradrenaline remain the critical mediators of renal arterial and arteriolar vasoconstriction, other novel molecules have been recently implicated. Although the above-described mechanistic pathway remains the backbone of the pathogenesis of HRS-1, other noxious elements may be present in advanced cirrhosis and likely contribute to the renal impairment. Direct liver-kidney crosstalk via the hepatorenal sympathetic reflex can further reduce renal blood flow independently of the systemic derangements. Tense ascites may lead to intraabdominal hypertension and abdominal compartment syndrome. Cardio-hemodynamic processes have also been increasingly recognized. Porto-pulmonary hypertension, cirrhotic cardiomyopathy, and abdominal compartment syndrome may lead to renal congestion and complicate the course of HRS-1. In addition, a degree of ischemic or toxic (cholemic) tubular injury may overlap with the underlying circulatory dysfunction and further exacerbate the course of acute kidney injury. Improving our understanding of the pathogenesis of HRS-1 may lead to improvements in therapeutic options for this seriously ill population.

Acute kidney injury in patients with cirrhosis: Acute Disease Quality Initiative (ADQI) and International Club of Ascites (ICA) joint multidisciplinary consensus meeting.

Patients with cirrhosis are prone to developing acute kidney injury (AKI), a complication associated with a markedly increased in-hospital morbidity and mortality, along with a risk of progression to chronic kidney disease. Whereas patients with cirrhosis are at increased risk of developing any phenotype of AKI, hepatorenal syndrome (HRS), a specific form of AKI (HRS-AKI) in patients with advanced cirrhosis and ascites, carries an especially high mortality risk. Early recognition of HRS-AKI is crucial since administration of splanchnic vasoconstrictors may reverse the AKI and serve as a bridge to liver transplantation, the only curative option. In 2023, a joint meeting of the International Club of Ascites (ICA) and the Acute Disease Quality Initiative (ADQI) was convened to develop new diagnostic criteria for HRS-AKI, to provide graded recommendations for the work-up, management and post-discharge follow-up of patients with cirrhosis and AKI, and to highlight priorities for further research.

A case of successful revascularization and renal recovery after 6 days of renal artery occlusion.

A 72-year-old man with peripheral arterial disease, an atrophic left kidney, and prior right renal chimney stent as part of a complex endovascular abdominal aortic aneurysm repair presented to our emergency department with right flank pain and anuria resulting from right artery occlusion. His serum creatinine on admission was 7.5 mg/dL. Computed tomography angiography 6 days after the onset of his symptoms revealed complete occlusion of the right renal artery stent. Percutaneous thrombectomy was performed restored renal blood flow. The urine flow started the following day, and his serum creatinine decreased to 3.5 mg/dL 7 days after discharge.

Kidney Dysfunction in the Setting of Liver Failure: Core Curriculum 2024.

Individuals with liver disease are susceptible to pathophysiological derangements that lead to kidney dysfunction. Patients with advanced cirrhosis and acute liver failure (ALF) are at risk of developing acute kidney injury (AKI). Hepatorenal syndrome type 1 (HRS-1, also called HRS-AKI) constitutes a form of AKI unique to the state of cirrhosis and portal hypertension. Although HRS-1 is a condition primarily characterized by marked renal vasoconstriction and kidney hypoperfusion, other pathogenic processes, such as acute tubular injury and renal vein congestion, can overlap and further complicate the course of HRS-1. ALF can lead to AKI through mechanisms that involve systemic inflammation, direct drug toxicity, or bile acid-induced tubulopathy. In addition, the growing prevalence of nonalcoholic steatohepatitis is changing the spectrum of chronic kidney disease in cirrhosis. In this installment of AJKD's Core Curriculum in Nephrology, we explore the underpinnings of how cirrhosis, ALF, acute cholestasis, and post-liver transplantation can be associated with various forms of acute, subacute, or chronic kidney diseases. We navigate through the recommended therapies for each condition, including supportive care, pharmacological interventions, kidney replacement therapy, and organ transplantation. Finally, key acid-base and electrolyte disorders associated with hepatobiliary disease are also summarized.

Massive Renal Cyst Displacing Intra-Abdominal Structures.

Background: Simple renal cysts typically produce no symptoms or signs and are usually detected incidentally on imaging studies for unrelated causes. Massive renal cysts are very rare. Case Report: A 77-year-old female with preexisting chronic kidney disease presented to our hospital for evaluation of hyperkalemia, abdominal distension, and right flank pain. Upon arrival, her vital signs and physical examination were normal. Laboratory data were pertinent for a serum creatinine of 4.8 mg/dL (6 months prior to presentation, serum creatinine was 1.5 mg/dL, and 1 month after discharge, it was 4.6 mg/dL), and hyperkalemia of 6.0 mmol/L. Computed tomography revealed a massive right renal cyst measuring 22 × 11 × 17.5 cm and displacing the intra-abdominal structures. Because of her symptoms, the patient was evaluated by urology for surgical management. The patient refused invasive procedures and chose pain control and monitoring. Conclusion: Noninvasive treatment options for a massive simple renal cyst are limited. Symptomatic treatment and monitoring the cyst size on a regular basis might be helpful for patients who refuse invasive treatment.

Impact of Proteinuria and Kidney Function Decline on Health Care Costs and Resource Utilization in Adults With IgA Nephropathy in the United States: A Retrospective Analysis.

Rationale & Objective: Among patients with IgA nephropathy (IgAN), proteinuria and decline in kidney function may be associated with increased economic burden. This study aimed to provide current information on the epidemiology and economic burden of IgAN in the United States. Study Design: Retrospective cohort study. Setting & Study Population: Overall, 9,984 patients in the Optum's Market Clarity database identified by the presence of at least 2 natural language processing-derived IgAN signs and disease and symptoms terms; 813 with linked claims data included in a health care resource utilization/cost subcohort. Predictor: High-risk proteinuria (≥1 g/d), chronic kidney disease (CKD) stage. Outcomes: Standardized prevalence, health care resource utilization, costs. Analytical Approach: Descriptive statistics for categorical and continuous variables. Direct standardization for prevalence estimation. Generalized linear models for health care resource utilization/costs, reported as per-patient-per-month (PPPM) costs in 2020 US dollars. Results: The estimated standardized US prevalence of IgAN (2016-2020) was 329.0 per 1,000,000 persons. High-risk proteinuria (≥1 vs <1 g/d) was associated with a higher mean PPPM number of outpatient visits (3.49 vs 1.74; P = 0.01) and pharmacy claims (3.79 vs 2.41; P = 0.01), contributing to higher mean total costs PPPM ($3,732 vs $1,457; P = 0.01). Furthermore, higher CKD stage was also associated with higher health care resource utilization (number of outpatient visits PPPM, number of pharmacy claims PPPM, proportion of patients with inpatient visits and emergency department visits; P < 0.001) and mean total cost PPPM (from $2,111 CKD stage 1 to $10,703 CKD stage 5/kidney failure; P < 0.001). Limitations: Generalizability outside of the catchment group for the database, missing data/errors inherent in retrospective database studies, relatively small sample size, use of Optum Market Clarity standardized pricing algorithms, exclusion of out-of-pocket costs. Conclusions: Health care resource utilization and costs were higher for IgAN patients with high-risk proteinuria and worsening kidney function. Treatments that reduce proteinuria and slow CKD disease progression may reduce the economic burden associated with IgAN. Plain-Language Summary: Immunoglobulin A nephropathy (IgAN) is a rare kidney disease. Over time, the kidneys may leak protein into the urine (proteinuria). IgAN can lead to kidney failure. Because IgAN is rare, it is hard to know how many people have it. This study used electronic health records to estimate the number of patients with IgAN in the United States, describe the characteristics of patients, and understand their treatments and the costs. The number of patients with IgAN increased between 2016 and 2020. The researchers think this is because doctors learned more about IgAN. Patients with severe disease used more health care resources and had higher costs. The authors believe treatments that slow kidney damage may reduce the cost of treating IgAN.

Incidence and outcomes of acute kidney injury including hepatorenal syndrome in hospitalized patients with cirrhosis in the US.

BACKGROUND & AIMS: Acute kidney injury (AKI) in cirrhosis is common and associated with high morbidity, but the incidence rates of different etiologies of AKI are not well described in the US. We compared incidence rates, practice patterns, and outcomes across etiologies of AKI in cirrhosis. METHODS: We performed a retrospective cohort study of 11 hospital networks, including consecutive adult patients admitted with AKI and cirrhosis in 2019. The etiology of AKI was adjudicated based on pre-specified clinical definitions (prerenal/hypovolemic AKI, hepatorenal syndrome [HRS-AKI], acute tubular necrosis [ATN], other). RESULTS: A total of 2,063 patients were included (median age 62 [IQR 54-69] years, 38.3% female, median MELD-Na score 26 [19-31]). The most common etiology was prerenal AKI (44.3%), followed by ATN (30.4%) and HRS-AKI (12.1%); 6.0% had other AKI, and 7.2% could not be classified. In our cohort, 8.1% of patients received a liver transplant and 36.5% died by 90 days. The lowest rate of death was observed in patients with prerenal AKI (22.2%; p <0.001), while death rates were higher but not significantly different from each other in those with HRS-AKI and ATN (49.0% vs. 52.7%; p = 0.42). Using prerenal AKI as a reference, the adjusted subdistribution hazard ratio (sHR) for 90-day mortality was higher for HRS-AKI (sHR 2.78; 95% CI 2.18-3.54; p <0.001) and ATN (sHR 2.83; 95% CI 2.36-3.41; p <0.001). In adjusted analysis, higher AKI stage and lack of complete response to treatment were associated with an increased risk of 90-day mortality (p <0.001 for all). CONCLUSION: AKI is a severe complication of cirrhosis. HRS-AKI is uncommon and is associated with similar outcomes to ATN. The etiology of AKI, AKI stage/severity, and non-response to treatment were associated with mortality. Further optimization of vasoconstrictors for HRS-AKI and supportive therapies for ATN are needed. IMPACT AND IMPLICATIONS: Acute kidney injury (AKI) in cirrhosis carries high morbidity, and management is determined by the etiology of injury. However, a large and well-adjudicated multicenter database from US centers that uses updated AKI definitions is lacking. Our findings demonstrate that acute tubular necrosis and hepatorenal syndrome have similar outcomes (∼50% mortality at 90 days), though hepatorenal syndrome is uncommon (12% of all AKI cases). These findings represent practice patterns at US transplant/tertiary centers and can be used as a baseline, presenting the situation prior to the adoption of terlipressin in the US.

Personal and Work-Related Burnout Is Associated with Elevated Diastolic Blood Pressure and Diastolic Hypertension among Working Adults in Chile.

We aimed at investigating the association of personal and work-related burnout with blood pressure and hypertension among working adults in Chile. We conducted a cross-sectional study among 1872 working adults attending the Hospital del Trabajador in Santiago, Chile, between September 2015 and February 2018. The Copenhagen Burnout Inventory was used to assess personal and work-related burnout. Blood pressure was measured by medical practitioners. Multivariable linear and logistic regressions were used to estimate the association of burnout status with systolic blood pressure (SBP), diastolic blood pressure (DBP), and hypertension. After adjusting for confounders, participants with both types of burnout had a 1.66 (95% confidence interval [CI]: 0.02-3.30) mmHg higher mean DBP than those without burnout. The odds of isolated diastolic hypertension among the participants with only personal burnout and both types of burnout were 2.00-fold (odds ratio [OR] = 2.00; 95% CI: 1.21-3.31) and 2.08-fold (OR = 2.08; 95% CI: 1.15-3.78) higher than those without burnout. The odds of combined systolic/diastolic hypertension among the participants with only work-related burnout increased by 59% (OR = 1.59; 95% CI: 1.01-2.50) compared with those without burnout. Both work-related and personal burnouts were associated with increased DBP and odds of diastolic hypertension among working adults in Chile.

Direct Oral Anticoagulants Versus Warfarin for Venous Thromboembolism Prophylaxis in Patients With Nephrotic Syndrome: A Retrospective Cohort Study.

BACKGROUND: Evidence supporting venous thromboembolism (VTE) prophylaxis with direct oral anticoagulants (DOACs) in patients with nephrotic syndrome (NS) is limited to case reports. OBJECTIVE: The purpose of this study was to compare bleeding and thromboembolic events in this population. METHODS: A retrospective cohort study was conducted in adults with NS initiated on a DOAC or warfarin for VTE prophylaxis between January 2013 and July 2021 within the Ochsner Health System. Patients with study drug exposure within the preceding 7 days, acute VTE within the preceding 6 months, or ≤7 days of study drug exposure were excluded. The primary outcome was the composite rate of major bleeding and clinically relevant nonmajor bleeding. Secondary outcomes included time to major bleeding and rate of new thromboembolic events. This study was approved by the Ochsner Health System Institutional Review Board. RESULTS: Twenty-five DOAC and 19 warfarin patients were included. The primary outcome occurred in 8% vs 26.3% (P = 0.21) of patients treated with a DOAC or warfarin, respectively, and was driven by major bleeding (4% vs 21%, P = 0.25). Other secondary outcomes were similar between cohorts. The study was limited by a small sample size. CONCLUSION AND RELEVANCE: Use of DOACs for VTE prophylaxis resulted in a nonstatistically significant, but clinically relevant lower rate of major bleeding compared to warfarin. This study provides comparative data showing safe and effective use of DOACs in patients with NS. Prospective, randomized studies are needed to confirm results.