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.

The Challenges of Diagnosing Nondilated Obstructive Uropathy: A Case Report.

Rationale: Nondilated obstructive uropathy (NDOU) is a rare cause of acute renal failure reported in less than 5% of cases of obstructive uropathy. It is typically associated with intrapelvic malignancies and diseases causing retroperitoneal lymphadenopathy and retroperitoneal fibrosis. As these conditions may prevent radiographic dilation of the collecting system, the diagnosis of NDOU may be missed by usual diagnostic testing. Presenting concerns of the patient: We present a case of acute anuric renal failure in a middle-aged woman with metastatic breast cancer associated with abdominal and retroperitoneal lymphadenopathy. Acute kidney injury was initially deemed secondary to drug-induced acute tubular necrosis (ATN) from bisphosphonate; however, there remained a high clinical suspicion of NDOU due to the presence of enlarged retroperitoneal lymph nodes on CT abdomen and pelvis with concerns for encasement of bilateral renal pelvic regions and ureters. Diagnoses: The patient underwent a retrograde pyelogram which demonstrated questionable narrowing bilaterally at the level of the renal pelvices. This led to an even stronger clinical suspicion of NDOU and urology service was consulted for evaluation. Intervention: Bilateral ureteral stents were placed by urology which led to robust urine output and rapid reversal of renal failure over the next 24 to 48 hours. Outcomes: Despite 2 weeks of anuria and hemodialysis, this patient's creatinine came back to her baseline. She was able to discontinue hemodialysis and her creatinine stabilized at 88.4 µmol/L (1 mg/dL). Teaching points: Nondilated obstructive uropathy is rare but important diagnosis that requires a high clinical suspicion in the appropriate clinical scenario. The lack of dilatation is believed to be related to encasement of the collecting system by tumor, fibrosis, or as in our case metastatic retroperitoneal lymphadenopathy. As this diagnosis cannot be overlooked, aggressive direct visualization or even intervention with internal or external stenting may be required to both diagnose and treat this condition.

Justification: L'uropathie obstructive sans dilatation (UOSD) est une cause rare d'insuffisance rénale aiguë (IRA) rapportée dans moins de 5 % des cas d'uropathie obstructive. Elle est généralement associée à des tumeurs malignes intrapelviennes et de maladies entraînant une lymphadénopathie rétropéritonéale et une fibrose rétropéritonéale. Ces conditions pouvant empêcher la dilatation radiographique du système collecteur, il arrive que le diagnostic de l'UOSD soit manqué lors des tests de diagnostic habituels. Présentation du cas: Nous présentons un cas d'IRA anurique chez une femme d'âge moyen atteinte d'un cancer du sein métastatique associé à une lymphadénopathie abdominale et rétropéritonéale (LAR). L'IRA avait initialement été considérée comme secondaire à une nécrose tubulaire aiguë induite par le bisphosphonate. La présence de ganglions lymphatiques rétropéritonéaux hypertrophiés sur la tomographie de l'abdomen et du bassin a toutefois soulevé un doute clinique d'UOSD; une obstruction des régions bilatérales du bassinet rénal et des uretères a été soupçonné. Diagnostic: La patiente a subi un pyélogramme rétrograde qui a montré un rétrécissement bilatéral suspect au niveau des bassinets rénaux, ce qui a soulevé un doute clinique encore plus important quant à la présence d'une UOSD. Le service d'urologie a été consulté pour évaluation. Intervention: Des endoprothèses urétérales ont été insérées bilatéralement par urologie. L'intervention a entraîné une forte production d'urine et la disparition de l'insuffisance rénale dans les 24 à 48 heures suivantes. Résultats: Malgré deux semaines d'anurie et d'hémodialyse, le taux de créatinine de la patiente est retourné à sa valeur initiale. La patiente a pu interrompre l'hémodialyse et son taux de créatinine s'est stabilisé à 88,4 micromoles/L (1 mg/dl). Enseignements tirés: Le diagnostic de l'UOSD est rare, mais important, car il requiert un doute clinique élevé dans le scénario clinique approprié. On pense que l'absence de dilatation pourrait être liée à l'obstruction du système collecteur rénal par une tumeur ou en raison d'une fibrose ou, comme ici, d'une lymphadénopathie rétropéritonéale métastatique. Puisque le diagnostic de l'UOSD ne doit pas être négligé, une visualisation directe plus poussée et l'insertion d'une endoprothèse interne ou externe pourraient s'avérer nécessaires pour diagnostiquer et traiter cette affection.

Successful treatment of refractory hypertension with bilateral nephrectomy in a patient with chronic kidney disease stage 3.

We present a case of life-threatening refractory hypertension (rHTN) in a patient with stage 3b chronic kidney disease that was unresponsive to open surgical renal denervation (RDN) but responded to bilateral nephrectomy (BLN). Both RDN and BLN reduce the increased sympathetic activation in rHTN. However, RDN has yet to show reductions in blood pressure adequate for the average patient with rHTN, and BLN has thus far been reserved for patients with preexisting end-stage kidney disease (ESKD). Our case suggests that there are patients with rHTN that warrant consideration of BLN prior to developing ESKD.

Use of Intravenous Gadolinium-Based Contrast Media in Patients With Kidney Disease: Consensus Statements from the American College of Radiology and the National Kidney Foundation.

Inaugural consensus statements were developed and endorsed by the American College of Radiology (ACR) and National Kidney Foundation to improve and standardize the care of patients with kidney disease who have indication(s) to receive ACR-designated group II or group III intravenous gadolinium-based contrast media (GBCM). The risk of nephrogenic systemic fibrosis (NSF) from group II GBCM in patients with advanced kidney disease is thought to be very low (zero events following 4931 administrations to patients with estimated glomerular filtration rate [eGFR] <30 mL/min per 1.73 m2; upper bounds of the 95% confidence intervals: 0.07% overall, 0.2% for stage 5D chronic kidney disease [CKD], 0.5% for stage 5 CKD and no dialysis). No unconfounded cases of NSF have been reported for the only available group III GBCM (gadoxetate disodium). Depending on the clinical indication, the potential harms of delaying or withholding group II or group III GBCM for an MRI in a patient with acute kidney injury or eGFR less than 30 mL/min per 1.73 m2 should be balanced against and may outweigh the risk of NSF. Dialysis initiation or alteration is likely unnecessary based on group II or group III GBCM administration.

Use of Intravenous Gadolinium-based Contrast Media in Patients with Kidney Disease: Consensus Statements from the American College of Radiology and the National Kidney Foundation.

Inaugural consensus statements were developed and endorsed by the American College of Radiology (ACR) and the National Kidney Foundation to improve and standardize the care of patients with kidney disease who have indication(s) to receive ACR-designated group II or group III intravenous gadolinium-based contrast media (GBCM). The risk of nephrogenic systemic fibrosis (NSF) from group II GBCM in patients with advanced kidney disease is thought to be very low (zero events following 4931 administrations to patients with estimated glomerular filtration rate [eGFR] <30 mL/min per 1.73 m2; upper bounds of the 95% confidence intervals: 0.07% overall, 0.2% for stage 5D chronic kidney disease [CKD], 0.5% for stage 5 CKD and no dialysis). No unconfounded cases of NSF have been reported for the only available group III GBCM (gadoxetate disodium). Depending on the clinical indication, the potential harms of delaying or withholding group II or group III GBCM for an MRI in a patient with acute kidney injury or eGFR less than 30 mL/min per 1.73 m2 should be balanced against and may outweigh the risk of NSF. Dialysis initiation or alteration is likely unnecessary based on group II or group III GBCM administration. This article is a simultaneous joint publication in Radiology and Kidney Medicine. The articles are identical except for stylistic changes in keeping with each journal's style. Either version may be used in citing this article.

Use of Intravenous Iodinated Contrast Media in Patients With Kidney Disease: Consensus Statements from the American College of Radiology and the National Kidney Foundation.

Intravenous iodinated contrast media are commonly used with CT to evaluate disease and to determine treatment response. The risk of acute kidney injury (AKI) developing in patients with reduced kidney function following exposure to intravenous iodinated contrast media has been overstated. This is due primarily to historic lack of control groups sufficient to separate contrast-induced AKI (CI-AKI; ie, AKI caused by contrast media administration) from contrast-associated AKI (CA-AKI; ie, AKI coincident to contrast media administration). Although the true risk of CI-AKI remains uncertain for patients with severe kidney disease, prophylaxis with intravenous normal saline is indicated for patients who have AKI or an estimated glomerular filtration rate less than 30 mL/min/1.73 m2 who are not undergoing maintenance dialysis. In individual high-risk circumstances, prophylaxis may be considered in patients with an estimated glomerular filtration rate of 30-44 mL/min/1.73 m2 at the discretion of the ordering clinician.

Use of Intravenous Iodinated Contrast Media in Patients with Kidney Disease: Consensus Statements from the American College of Radiology and the National Kidney Foundation.

Intravenous iodinated contrast media are commonly used with CT to evaluate disease and to determine treatment response. The risk of acute kidney injury (AKI) developing in patients with reduced kidney function following exposure to intravenous iodinated contrast media has been overstated. This is due primarily to historic lack of control groups sufficient to separate contrast-induced AKI (CI-AKI; ie, AKI caused by contrast media administration) from contrast-associated AKI (CA-AKI; ie, AKI coincident to contrast media administration). Although the true risk of CI-AKI remains uncertain for patients with severe kidney disease, prophylaxis with intravenous normal saline is indicated for patients who have AKI or an estimated glomerular filtration rate less than 30 mL/min/1.73 m2 who are not undergoing maintenance dialysis. In individual high-risk circumstances, prophylaxis may be considered in patients with an estimated glomerular filtration rate of 30-44 mL/min/1.73 m2 at the discretion of the ordering clinician. This article is a simultaneous joint publication in Radiology and Kidney Medicine. The articles are identical except for stylistic changes in keeping with each journal's style. Either version may be used in citing this article.

Percutaneous Renal Biopsy Using an 18-Gauge Automated Needle Is Not Optimal.

BACKGROUND: As percutaneous renal biopsies (PRBs) are increasingly performed by radiologists, an increase in the use of 18-gauge automated needle stands to compromise adequacy. We compare the adequacy and safety of PRB with 14-, 16-, and 18-gauge automated needles. METHODS: PRB of native (N-592) and transplant (T-1,023) kidneys was performed from January 2002 to December 2019 using real-time ultrasound. Baseline clinical and laboratory data, biopsy data (number of cores, total glomeruli, and total glomeruli per core), and outcome (hematoma on renal US at 1-h, complications, and transfusion) were collected prospectively. PRB with N14g (337) versus N16g (255) and T16g (892) versus T18g (131) needles were compared. A p value of <0.05 was significant. RESULTS: PRB with an 18-g needle yielded the lowest number of total glomeruli per biopsy (N14g vs. N16g: 33 ± 13 vs. 29 ± 12, p < 0.01 and T16g vs. T18g: 34 ± 16 vs. 21 ± 11, p < 0.0001), significantly fewer total glomeruli per core (T16g vs. T18g: 12.7 ± 6.4 vs. 9.6 ± 5.0, p < 0.001 and N16g vs. T18g: 14.2 ± 6.3 vs. 9.6 ± 5.0, p < 0.001). A hematoma by renal US 1-h post-PRB was similar for native (14g-35% vs. 16g-29%, p = 0.2), and transplant biopsies (16g-10% vs. 18g-9%, p = 0.9) and the complication rate for native (14g-8.9% vs. 16g-7.1%, p = 0.5), transplant biopsies (16g-4.6% vs. 18g-1.5%, p = 0.2) and transfusion rate for native (14g-7.7% vs. 16g-5.8%, p = 0.4), and transplant biopsies (16g-3.8% vs. 18g-0.8%, p = 0.1) were similar irrespective of needle size. CONCLUSIONS: PRB of native and transplant kidneys with the use of a 16-gauge needle provides an optimal sample. However, our experience in transplant biopsies suggests the use of an 18-gauge needle stands to jeopardize the diagnostic accuracy of the PRB while not improving safety.

Changing Trends in the Performance of Percutaneous Renal Biopsy from Nephrologist to Interventional Radiologist: A Single-Center Experience.

BACKGROUND: Percutaneous renal biopsy of native kidneys (PRB) has been an integral part of the practice of nephrology. However, over the past 30 years, PRB has transitioned from a procedure performed only by nephrologists to interventional radiologists (IRs). We surveyed practicing nephrologists completing training in our program to determine the clinical practice patterns of PRB. METHODS: The 78 fellows completing the nephrology program at Rush University Medical Center from June 1984 through June 2017 were successfully contacted and surveyed regarding their opinion on adequacy of their training and whether they performed PRB in practice and if not or no longer, why. To evaluate for differences in the performance of PRB over time, a comparison of 4 periods of fellowship completion (i.e., 1984-1990, 1991-2000, 2001-2010, 2011-2017) was performed. RESULTS: All 78 nephrologists felt they had been adequately trained to perform PRB. PRB was performed by 45 (58%) nephrologists post-fellowship, but a significant decline was observed over the 4 periods of time from 1984 to 2017 (100 vs. 86 vs. 52 vs. 20%, p < 0.0001). The primary reason that 33 nephrologists did not perform PRB was that it was too time consuming and IR was available to perform PRB. Of the 71 nephrologists still in practice only 12 (17%) continue to perform PRB. A greater proportion of nephrologists completing training from 1984-1990 continue to perform PRB relative to those trained after 1990. The universal reason that nephrologists were no longer performing PRB was again an issue of time and the fact that IRs were available to perform PRB. CONCLUSION: We find that there has been a significant transition over time in the performance of PRB by a nephrologist to IR. The major reason for this is the time burden associated with PRB and the availability of IRs.

Ferric Citrate, an Iron-Based Phosphate Binder, Reduces Health Care Costs in Patients on Dialysis Based on Randomized Clinical Trial Data.

BACKGROUND: Patients with end-stage renal disease (ESRD) require phosphate binders for hyperphosphatemia and erythropoiesis-stimulating agents (ESAs) and intravenous (i.v.) iron for anemia. Ferric citrate (FC) is a novel, iron-based phosphate binder that increases iron stores and decreases i.v. iron and ESA usage while maintaining hemoglobin levels, and may decrease the cost of ESRD care. The study objectives were to (1) quantify differences in ESA and i.v. iron usage among ESRD patients receiving FC compared with active control (AC) (sevelamer carbonate and/or calcium acetate) on the basis of data from a 52-week phase III clinical trial and (2) standardize trial data to the general United States (US) ESRD population and calculate the potential impact of FC on ESRD cost/patient/year in the USA. STUDY DESIGN: The study was a randomized, controlled clinical trial. SETTING AND POPULATION: A total of 441 adult subjects with ESRD who received FC or AC for 52 weeks were included. MODEL, PERSPECTIVE, AND TIMELINE: Differences in ESA and i.v. iron usage between the treatment groups were modeled over time using generalized linear mixed models and zero-inflated Poisson models. Trends were modeled via logarithmic curves, and utilization patterns were applied to the general dialysis population to estimate expected resource savings. OUTCOMES: Study outcomes were costs saved/patient/year using FC versus AC (US dollars). RESULTS: Our model suggests an annual decrease of 129,106 U of ESAs and 1960 mg of i.v. iron per patient in the second year after a switch from AC to FC. Applying 2013 Medicare pricing, this would save $1585 in ESAs and $516 in i.v. iron: a total of $2101/patient/year; these savings would be expected to double for managed care plans. LIMITATIONS: The projections were made on 1 year of trial data. CONCLUSIONS: Phosphate binding with FC reduces i.v. iron and ESA usage. Given the high cost burden of ESRD, our model demonstrates significant potential cost savings. TRIAL REGISTRATION: ClinicalTrials.gov (NCT01191255) http://clinicaltrials.gov/ct2/show/NCT01191255 .

Disease-specific patient reported outcome tools for systemic lupus erythematosus.

PURPOSE: Systemic lupus erythematosus (SLE) can significantly affect both health and non-health-related quality of life (HRQOL and non-HRQOL). However, of the existent published patient-reported outcome (PRO) tools, none were developed from US patients, an ethnically diverse population. Furthermore, these tools do not address men with SLE or assess non-HRQOL issues. Herein, we present the development and validation of the Lupus Patient-Reported Outcome tool (LupusPRO) and discuss its clinical utility and research value compared with other PRO tools currently available for SLE. METHODS: Beginning with a conceptual framework, items for LupusPRO were generated using feedback from women and men with SLE. The tool underwent iterations based on patient feedback and clinimetric and psychometric analyses. Validity (content, construct, and criterion) and reliability (internal consistency and test-retest) for the 44-item LupusPRO tool are presented. RESULTS: Consistent with the conceptual framework, items were identified that were related to HRQOL and non-HRQOL constructs. HRQOL domains included (1) lupus symptoms; (2) physical health (physical function, role physical); (3) pain-vitality; (4) emotional health (emotional function and role emotional); (5) body image; (6) cognition; (7) procreation; and (8) lupus medications. Non-HRQOL domains were (1) available social support and coping; (2) desires-goals; and (3) satisfaction with medical care. Internal consistency reliability (0.68-0.94), test-retest reliability (0.55-0.92), content, construct (r > 0.50 with SF-36), and criterion (r > -0.35 with disease activity) validity were fair to good. CONCLUSIONS: LupusPRO is a valid and reliable disease-targeted patient-reported health outcome tool that is generalizable to SLE patients in the United States of varied ethnic backgrounds and either gender.