The evolution of performing a kidney biopsy: a single center experience comparing native and transplant kidney biopsies performed by interventional radiologists and nephrologists.

BACKGROUND: Kidney biopsy is the most vital tool guiding a nephrologist in diagnosis and treatment of kidney disease. Over the last few years, we have seen an increasing number of kidney biopsies being performed by interventional radiologists. The goal of our study was to compare the adequacy and complication rates between kidney biopsies performed by interventional radiology versus nephrology.  METHODS : We performed a single center retrospective analysis of a total of all kidney biopsies performed at our Institution between 2015 and 2021. All biopsies were performed using real-time ultrasound. Patients were monitored for four hours post biopsy and repeat ultrasound or hemoglobin checks were done if clinically indicated. The entire cohort was divided into two groups (Interventional radiology (IR) vs nephrology) based on who performed the biopsy. Baseline characteristics, comorbidities, blood counts, blood pressure, adequacy of the biopsy specimen and complication rates were recorded. Multivariable logistic regression was used to compare complication rates (microscopic hematuria, gross hematuria and need for blood transfusion combined) between these two groups, controlling for covariates of interest. ANCOVA (analysis of variance, controlling for covariates) was used to compare differences in biopsy adequacy (number of glomeruli per biopsy procedure) between the groups. RESULTS: 446 kidney biopsies were performed in the study period (229 native and 147 transplant kidney biopsies) of which 324 were performed by IR and 122 by nephrologist. There was a significantly greater number of core samples obtained by IR (mean = 3.59, std.dev. = 1.49) compared to nephrology (mean = 2.47, std.dev = 0.79), p < 0.0001. IR used 18-gauge biopsy needles while nephrologist exclusively used 16-gauge needles. IR used moderate sedation (95.99%) or general anesthesia (1.85%) for the procedures more often than nephrology, which used them only in 0.82% and 0.82% of cases respectively (p < 0.0001). Trainees (residents or fellows) participated in the biopsy procedures more often in nephrology compared to IR (97.4% versus 69.04%, p < 0.0001). The most frequent complication identified was microscopic hematuria which occurred in 6.8% of biopsies. For native biopsies only, there was no significant difference in likelihood of complication between groups, after adjustment for covariates of interest (OR = 1.01, C.I. = (0.42, 2.41), p = 0.99). For native biopsies only, there was no significant difference in mean number of glomeruli obtained per biopsy procedure between groups, after adjustment for covariates of interest (F(1,251) = 0.40, p = 0.53). CONCLUSION: Our results suggest that there is no significant difference in the adequacy or complication rates between kidney biopsies performed by IR or nephrology. This conclusion may indicate that kidney biopsies can be performed safely with adequate results either by IR or nephrologists depending on each institution's resources and expertise.

Lipoic acid supplementation associated with neural epidermal growth factor-like 1 (NELL1)-associated membranous nephropathy.

Lipoic acid (alpha lipoic acid, thioctic acid) is a popular over-the-counter antioxidant and insulin-mimetic supplement under investigation in a variety of conditions including multiple sclerosis, diabetes, and schizophrenia. Unfortunately, high-grade proteinuria was an unexpected adverse event specific to the treatment arm of our clinical trial investigating lipoic acid supplementation in patients with multiple sclerosis. This observation led to detection of similar patients in our nephrology practice. Here, we describe four biopsy-proven cases of neural epidermal growth factor-like 1 (NELL1)-associated membranous nephropathy following lipoic acid supplementation and a fifth suspected case. Discontinuation of lipoic acid and supportive therapy resulted in remission.

Impact of age mismatch between donor and recipient on heart transplant mortality.

The effect of donor-to-recipient (D-R) age mismatch in adult heart transplant population is not clearly described, and we undertook this study to determine the impact of age mismatch on mortality. Heart transplant recipients from 2000 to 2017 were identified using the United Network of Organ Sharing database. The cohort was divided into three groups: donor age within 5 years of recipient age (Group 1), donors >5 years younger than recipient (group 2), and donors >5 years older than recipients (Group 3). We also evaluated if this finding changed by recipient age. Twenty eight thousand, four hundred and eleven patients met the inclusion criteria. Compared to group 1, the adjusted hazard ratio (aHR) for mortality for group 2 was 0.91 (0.83-0.99, p value <.039) and for group 3 was 1.36 (1.21-1.52, p value <.001); however, when looking at recipient age as continuous variable, receiving a younger heart was protective only for recipients younger than 45 years of age, and receiving a heart transplant from an older donor was detrimental only in recipients aged 25-35.

Real-time measurement of glomerular filtration rate.

PURPOSE OF REVIEW: Measurement of glomerular filtration rate is an essential tool for determining the health or dysfunction of the kidney. The glomerular filtration rate is a dynamic function that can change almost instantaneously in response to stressors. Despite its central role in nephrology, there are no techniques available to the clinician for monitoring glomerular filtration rate in real time. Recent advances in technology to measure fluorescent compounds through the skin are providing a new approach for real-time monitoring of glomerular filtration rate. This review frames these technologies within how such measurements might be used in clinical medicine. RECENT FINDINGS: Fluorescent molecules that act as ideal filtration markers are now available. Using transdermal sensors, the plasma disappearance rate of these exogenous markers can be measured rather than their steady state concentration. This eliminates the delay inherent in using an endogenous marker of filtration and permits continuous monitoring of GFR. SUMMARY: These new technologies provide enhanced opportunities for diagnosis of kidney dysfunction and therapeutic monitoring. Accurate assessment of measured GFR will eliminate the erroneous diagnosis of chronic kidney disease (CKD) from many patients. Assessment of renal reserve will provide a new risk factor for progression of CKD. Real-time monitoring of GFR in critically ill patients will allow for earlier diagnosis of acute kidney injury and a dynamic metric to guide therapeutics. These are but a few of the many opportunities that this new technology will provide in both the clinical and research arenas.

The optimal definition of contrast-induced acute kidney injury for prediction of inpatient mortality in patients undergoing percutaneous coronary interventions.

BACKGROUND: It is unknown which definition of contrast-induced acute kidney injury (CI-AKI) in the setting of percutaneous coronary interventions is best associated with inpatient mortality and whether this association is stable across patients with various preprocedural serum creatinine (SCr) values. METHODS: We applied logistic regression models to multiple CI-AKI definitions used by the Kidney Disease Improving Global Outcomes guidelines and previously published studies to examine the impact of preprocedural SCr on a candidate definition's correlation with the adverse outcome of inpatient mortality. We used likelihood ratio tests to examine candidate definitions and identify those where association with inpatient mortality remained constant regardless of preprocedural SCr. These definitions were assessed for specificity, sensitivity, and positive and negative predictive values to identify an optimal definition. RESULTS: Our study cohort included 119,554 patients who underwent percutaneous coronary intervention in Michigan between 2010 and 2014. Most commonly used definitions were not associated with inpatient mortality in a constant fashion across various preprocedural SCr values. Of the 266 candidate definitions examined, 16 definition's association with inpatient mortality was not significantly altered by preprocedural SCr. Contrast-induced acute kidney injury defined as an absolute increase of SCr ≥0.3 mg/dL and a relative SCr increase ≥50% was selected as the optimal candidate using Perkins and Shisterman decision theoretic optimality criteria and was highly predictive of and specific for inpatient mortality. CONCLUSIONS: We identified the optimal definition for CI-AKI to be an absolute increase in SCr ≥0.3 mg/dL and a relative SCr increase ≥50%. Further work is needed to validate this definition in independent studies and to establish its utility for clinical trials and quality improvement efforts.

Hydration to Prevent Contrast-Associated Acute Kidney Injury in Patients Undergoing Cardiac Angiography.

Administration of fluid (oral and intravenous) is the cornerstone of prevention of contrast-associated acute kidney injury in the cardiac environment. Intravenous saline is the preferred fluid. The amount, timing, and duration of therapy are discussed. A key determinant of the benefit may be the rate of urine output stimulated by the therapy. Approaches using hemodynamic-guided rates of fluid administration and novel techniques to generate large urine outputs while maintaining fluid balance are highlighted.

Team-Based Coaching Intervention to Improve Contrast-Associated Acute Kidney Injury: A Cluster-Randomized Trial.

BACKGROUND: Up to 14% of patients in the United States undergoing cardiac catheterization each year experience AKI. Consistent use of risk minimization preventive strategies may improve outcomes. We hypothesized that team-based coaching in a Virtual Learning Collaborative (Collaborative) would reduce postprocedural AKI compared with Technical Assistance (Assistance), both with and without Automated Surveillance Reporting (Surveillance). METHODS: The IMPROVE AKI trial was a 2×2 factorial cluster-randomized trial across 20 Veterans Affairs medical centers (VAMCs). Participating VAMCs received Assistance, Assistance with Surveillance, Collaborative, or Collaborative with Surveillance for 18 months to implement AKI prevention strategies. The Assistance and Collaborative approaches promoted hydration and limited NPO and contrast dye dosing. We fit logistic regression models for AKI with site-level random effects accounting for the clustering of patients within medical centers with a prespecified interest in exploring differences across the four intervention arms. RESULTS: Among VAMCs' 4517 patients, 510 experienced AKI (235 AKI events among 1314 patients with preexisting CKD). AKI events in each intervention cluster were 110 (13%) in Assistance, 122 (11%) in Assistance with Surveillance, 190 (13%) in Collaborative, and 88 (8%) in Collaborative with Surveillance. Compared with sites receiving Assistance alone, case-mix-adjusted differences in AKI event proportions were -3% (95% confidence interval [CI], -4 to -3) for Assistance with Surveillance, -3% (95% CI, -3 to -2) for Collaborative, and -5% (95% CI, -6 to -5) for Collaborative with Surveillance. The Collaborative with Surveillance intervention cluster had a substantial 46% reduction in AKI compared with Assistance alone (adjusted odds ratio=0.54; 0.40-0.74). CONCLUSIONS: This implementation trial estimates that the combination of Collaborative with Surveillance reduced the odds of AKI by 46% at VAMCs and is suggestive of a reduction among patients with CKD. CLINICAL TRIAL REGISTRY NAME AND REGISTRATION NUMBER: IMPROVE AKI Cluster-Randomized Trial (IMPROVE-AKI), NCT03556293.

Intrarenal oxygenation by blood oxygenation level-dependent MRI in contrast nephropathy model: effect of the viscosity and dose.

PURPOSE: To compare the effects of osmolality versus viscosity of radio-contrast media on intra-renal oxygenation as determined by blood oxygenation level-dependent (BOLD) MRI in a model of contrast induced nephropathy (CIN). MATERIALS AND METHODS: Twenty-four Sprague-Dawley rats were divided into five groups. Nitric oxide synthase inhibitor L-NAME (10 mg/kg), cyclooxygenase inhibitor indomethacin (10 mg/kg), or saline, and radio-contrast iodixanol (high viscosity, 784 or 1600 mg I/kg) or iothalamate (high osmolality, 1600 mg I/kg) were administered. BOLD MRI images were acquired on Siemens 3 Tesla (T) scanner using a multiple gradient recalled echo sequence at baseline, following L-NAME (or saline), indomethacin (or saline), and radio-contrast agents. R2* (=1/T2*) was used as the BOLD MRI parameter in renal medulla and cortex. Mixed-effects models with first order auto-regressive variance-covariance models were used to analyze the data. RESULTS: The magnitude of change in medullary R2* (MR2*) with same dose of iodine was larger with iodixanol compared with iothalalmate both in pretreated groups (303% versus 225.6%, < 0.01) and the control group (191.6% versus -1.8%, P < 0.01). The MR2* change in high dose iodixanol was approximately twice compared with the low dose (303% versus 133%, P < 0.01). CONCLUSION: The viscosity of radio-contrast seems to play a more significant role than osmolality in terms of renal oxygenation changes as evaluated by BOLD MRI. Additionally, iodixanol induced a dose-dependent increase in renal medullary hypoxia.

Maintaining a National Acute Kidney Injury Risk Prediction Model to Support Local Quality Benchmarking.

BACKGROUND: The utility of quality dashboards to inform decision-making and improve clinical outcomes is tightly linked to the accuracy of the information they provide and, in turn, accuracy of underlying prediction models. Despite recognition of the need to update prediction models to maintain accuracy over time, there is limited guidance on updating strategies. We compare predefined and surveillance-based updating strategies applied to a model supporting quality evaluations among US veterans. METHODS: We evaluated the performance of a US Department of Veterans Affairs-specific model for postcardiac catheterization acute kidney injury using routinely collected observational data over the 6 years following model development (n=90 295 procedures in 2013-2019). Predicted probabilities were generated from the original model, an annually retrained model, and a surveillance-based approach that monitored performance to inform the timing and method of updates. We evaluated how updating the national model impacted regional quality profiles. We compared observed-to-expected outcome ratios, where values above and below 1 indicated more and fewer adverse outcomes than expected, respectively. RESULTS: The original model overpredicted risk at the national level (observed-to-expected outcome ratio, 0.75 [0.74-0.77]). Annual retraining updated the model 5×; surveillance-based updating retrained once and recalibrated twice. While both strategies improved performance, the surveillance-based approach provided superior calibration (observed-to-expected outcome ratio, 1.01 [0.99-1.03] versus 0.94 [0.92-0.96]). Overprediction by the original model led to optimistic quality assessments, incorrectly indicating most of the US Department of Veterans Affairs' 18 regions observed fewer acute kidney injury events than predicted. Both updating strategies revealed 16 regions performed as expected and 2 regions increasingly underperformed, having more acute kidney injury events than predicted. CONCLUSIONS: Miscalibrated clinical prediction models provide inaccurate pictures of performance across clinical units, and degrading calibration further complicates our understanding of quality. Updating strategies tailored to health system needs and capacity should be incorporated into model implementation plans to promote the utility and longevity of quality reporting tools.

A randomized, double-blind, placebo-controlled trial of calcium acetate on serum phosphorus concentrations in patients with advanced non-dialysis-dependent chronic kidney disease.

BACKGROUND: Hyperphosphatemia in patients with chronic kidney disease (CKD) contributes to secondary hyperparathyroidism, soft tissue calcification, and increased mortality risk. This trial was conducted to examine the efficacy and safety of calcium acetate in controlling serum phosphorus in pre-dialysis patients with CKD. METHODS: In this randomized, double-blind, placebo-controlled trial, 110 nondialyzed patients from 34 sites with estimated GFR < 30 mL/min/1.73 m² and serum phosphorus > 4.5 mg/dL were randomized to calcium acetate or placebo for 12 weeks. The dose of study drugs was titrated to achieve target serum phosphorus of 2.7-4.5 mg/dL. Serum phosphorus, calcium, iPTH, bicarbonate and serum albumin were measured at baseline and every 2 weeks for the 12 week study period. The primary efficacy endpoint was serum phosphorus at 12 weeks. Secondary endpoints were to measure serum calcium and intact parathyroid hormone (iPTH) levels. RESULTS: At 12 weeks, serum phosphorus concentration was significantly lower in the calcium acetate group compared to the placebo group (4.4 ± 1.2 mg/dL vs. 5.1 ± 1.4 mg/dL; p = 0.04). The albumin-adjusted serum calcium concentration was significantly higher (9.5 ± 0.8 vs. 8.8 ± 0.8; p < 0.001) and iPTH was significantly lower in the calcium acetate group compared to placebo (150 ± 157 vs. 351 ± 292 pg/mL respectively; p < 0.001). At 12 weeks, the proportions of subjects who had hypocalcemia were 5.4% and 19.5% for the calcium acetate and the placebo groups, respectively, while the proportions of those with hypercalcemia were 13.5% and 0%, respectively. Adverse events did not differ between the treatment groups. CONCLUSIONS: In CKD patients not yet on dialysis, calcium acetate was effective in reducing serum phosphorus and iPTH over a 12 week period. TRIAL REGISTRATION: www.clinicaltrials.gov NCT00211978.

Antineutrophil Cytoplasmic Autoantibody-Associated Vasculitis with Kidney Involvement in a Patient with AL Amyloidosis.

Antineutrophil cytoplasmic autoantibody (ANCA) vasculitis has occasionally been associated with other systemic glomerulonephritis, such as anti-glomerular basement membrane disease. Here, we report the first clinical case of ANCA-associated crescentic glomerulonephritis with AL amyloidosis. An 81-years-old gentleman presented to the hospital with acute kidney injury (serum creatinine 4.7 mg/dL) on a background of chronic kidney disease and volume overload. Autoimmune serology was remarkable for p-ANCA and myeloperoxidase positivity. A renal biopsy confirmed pauci-immune glomerulonephritis and lambda light-chain amyloid deposition (confirmed on liquid chromatography and tandem mass spectrometry). The patient was initially managed with rituximab and subsequently transitioned to bortezomib-based chemotherapy but died due to decompensated heart failure. This case report promotes greater awareness of the unusual presentation of amyloidosis and guides future research and treatment.

Acute Kidney Injury and Renin-Angiotensin System Inhibition Following Transcatheter Aortic Valve Replacement.

OBJECTIVE: To identify renin-angiotensin system (RAS) inhibition utilization and discontinuation after transcatheter aortic valve replacement (TAVR) and identify predictors of use and discontinuation. BACKGROUND: RAS inhibition after TAVR has been associated with lower cardiac mortality and heart failure readmissions. METHODS: We analyzed 735 consecutive TAVR patients (2014-2019) who survived to hospital discharge at a high-volume TAVR center to determine the utilization and discontinuation of RAS inhibition after TAVR and identify predictors of use and discontinuation. Clinical characteristics, procedural variables, and hospital outcomes were compared between patients receiving vs not receiving discharge RAS inhibitors. Data were compared using t-test and Chi-square test. Multivariable analysis was used to determine independent clinical predictors. RESULTS: Of the 735 patients, 41.9% were discharged with at least 1 RAS inhibitor. In TAVR patients with heart failure with reduced ejection fraction (HFrEF), defined as EF ≤40%, the utilization of RAS inhibitors at discharge was 51.1%. Patients receiving discharge RAS inhibitors had lower incidences of acute kidney injury (AKI) post procedure (8.1% vs 17.8%; P<.01). Discontinuation of RAS inhibition was observed in approximately 1 in 3 patients and was associated with AKI and pacemaker requirement. Three predictors of RAS inhibitor utilization were higher systolic blood pressure, RAS inhibitor use prior to TAVR, and HFrEF. Conversely, new pacemaker and AKI were associated with less utilization of RAS inhibitors; patients developing AKI were 74% less likely to receive RAS inhibitors than those without AKI. CONCLUSION: Decreased RAS inhibition provides a potential mechanism for worse outcomes in TAVR patients who develop AKI.

Hydration: Intravenous and Oral: Approaches, Principals, and Differing Regimens: Is It What Goes in or What Comes Out That Is Important?

The literature (in English) was accessed to review the evidence that administration of fluids is protective of contrast-associated acute kidney injury (CA-AKI). The evidence was evaluated with the intent of understanding mechanisms of protection. Prospective randomized trials comparing oral versus intravenous fluid, sodium chloride versus no intravenous fluid, sodium bicarbonate versus sodium chloride, and forced matched hydration versus intravenous sodium chloride provided the data. In general, the more fluid administered, the lower the incidence of CA-AKI. However, understanding the mechanism of this beneficial effect suggests that it is the urine output that most directly affects the incidence of CA-AKI.

Effect of Low-Frequency Therapeutic Ultrasound on Induction of Nitric Oxide in CKD: Potential to Prevent Acute Kidney Injury.

INTRODUCTION: Post-contrast acute kidney injury (PC-AKI) develops in a significant proportion of patients with CKD after invasive cardiology procedures and is strongly associated with adverse outcomes. OBJECTIVE: We sought to determine whether increased intrarenal nitric oxide (NO) would prevent PC-AKI. METHODS: To create a large animal model of CKD, we infused 250 micron particles into the renal arteries in 56 ± 8 kg pigs. We used a low-frequency therapeutic ultrasound device (LOTUS - 29 kHz, 0.4 W/cm2) to induce NO release. NO and laser Doppler probes were used to assess changes in NO content and blood flow. Glomerular filtration rate (GFR) was measured by technetium-diethylene-triamine-pentaacetic acid (Tc-99m-DTPA) radionuclide imaging. PC-AKI was induced by intravenous infusion of 7 cm3/kg diatrizoate. In patients with CKD, we measured GFR at baseline and during LOTUS using Tc-99m-DTPA radionuclide imaging. RESULTS: In the pig model, CKD developed over 4 weeks (serum creatinine [Cr], mg/dL, 1.0 ± 0.2-2.6 ± 0.9, p < 0.01, n = 12). NO and renal blood flow (RBF) increased in cortex and medulla during LOTUS. GFR increased 75 ± 24% (p = 0.016, n = 3). PC-AKI developed following diatrizoate i.v. infusion (Cr 2.6 ± 0.7 baseline to 3.4 ± 0.6 at 24 h, p < 0.01, n = 3). LOTUS (starting 15 min prior to contrast and lasting for 90 min) prevented PC-AKI in the same animals 1 week later (Cr 2.5 ± 0.4 baseline to 2.6 ± 0.7 at 24 h, p = ns, n = 3). In patients with CKD (n = 10), there was an overall 25% increase in GFR in response to LOTUS (p < 0.01). CONCLUSIONS: LOTUS increased intrarenal NO, RBF, and GFR and prevented PC-AKI in a large animal model of CKD, and significantly increased GFR in patients with CKD. This novel approach may provide a noninvasive nonpharmacological means to prevent PC-AKI in high-risk patients.

Acute Kidney Recovery in Patients Who Underwent Transcatheter Versus Surgical Aortic Valve Replacement (from the Northern New England Cardiovascular Disease Study Group).

Acute kidney recovery (AKR) is a recently described phenomenon observed after transcatheter aortic valve replacement (TAVR) and is more frequent than acute kidney injury (AKI). To determine the incidence and predictors of AKR between surgical aortic valve replacement (SAVR) and TAVR, we examined patients with chronic kidney disease and severe aortic stenosis who underwent SAVR or TAVR procedure between 2007 and 2017; excluding age <65 or >90, dialysis, endocarditis, non-aortic valve stenosis, or patients died within 48-hours postprocedure. AKR was defined as an increase of estimated glomerular filtration rate (eGFR) >25% and AKI as decrease in eGFR >25% at discharge. Stroke, mortality, major bleeding, transfusion, and length of stay were examined. Multivariate logistic regression analysis was used to examine predictors of AKR. There were 750 transcatheter and 1,062 surgical patients and 319 pairs after propensity matching. AKR was observed in 26% TAVR versus 23.2% SAVR, p = 0.062. Highest recovery was in patients with eGFR <30 for both TAVR (33.7%) and SAVR (34.5%) patients. Independent predictors of AKR were ejection fraction <50% (odds ratio [OR] 1.66, 95% confidence interval [CI] 1.02 to 2.71, p = 0.042), female gender (OR 1.66, 95% CI 1.1 to 2.5, p = 0.015), and obesity (OR 1.5, 95% CI 1.04-2.3, p = 0.032). Diabetes was a negative predictor of AKR (OR 0.55, 95% CI 0.36 to 0.84, p = 0.005). AKR was associated with improved secondary clinical outcomes compared with AKI. In conclusion, AKR is a generalizable phenomenon occurring frequently and similarly among transcatheter or surgical aortic valve patients. Diabetes is a negative predictor of AKR, possibly indicative of less reversible kidney disease.