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 association between adult-onset Still's disease and collapsing glomerulopathy: a case report.

BACKGROUND: Collapsing glomerulopathy, characterized by marked hypertrophy and hyperplasia of the podocytes with eventual collapse of the glomerular tuft, is an important cause of end-stage renal disease. Among the many causes of collapsing glomerulopathy, autoimmune diseases, such as systemic lupus erythematosus, have been implicated. There are also rare reports of adult-onset Still's disease, an autoinflammatory condition characterized by fever, rash, and inflammatory arthritis being associated with collapsing glomerulopathy. CASE PRESENTATION: Herein, we present a review of three published cases, and present a new case of a 15-year-old African American female patient with collapsing glomerulopathy who was diagnosed with adult-onset Still's disease 12 years later when she presented with fevers, arthralgias, sore throat, lymphadenopathy, hepatocellular injury, and elevated serum ferritin. Her collapsing glomerulopathy was initially well controlled following induction therapy with cyclosporine and prednisone and maintenance therapy with losartan. However, after developing adult-onset Still's disease, she had multiple flare-ups despite various immunosuppressive therapies and developed worsening renal function, eventually progressing to end-stage renal disease. CONCLUSIONS: Our case-based review highlights a rare but important association between adult-onset Still's disease and collapsing glomerulopathy, and postulates a possible pathophysiological link.

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.

New Creatinine- and Cystatin C-Based Equations to Estimate GFR without Race.

BACKGROUND: Current equations for estimated glomerular filtration rate (eGFR) that use serum creatinine or cystatin C incorporate age, sex, and race to estimate measured GFR. However, race in eGFR equations is a social and not a biologic construct. METHODS: We developed new eGFR equations without race using data from two development data sets: 10 studies (8254 participants, 31.5% Black) for serum creatinine and 13 studies (5352 participants, 39.7% Black) for both serum creatinine and cystatin C. In a validation data set of 12 studies (4050 participants, 14.3% Black), we compared the accuracy of new eGFR equations to measured GFR. We projected the prevalence of chronic kidney disease (CKD) and GFR stages in a sample of U.S. adults, using current and new equations. RESULTS: In the validation data set, the current creatinine equation that uses age, sex, and race overestimated measured GFR in Blacks (median, 3.7 ml per minute per 1.73 m2 of body-surface area; 95% confidence interval [CI], 1.8 to 5.4) and to a lesser degree in non-Blacks (median, 0.5 ml per minute per 1.73 m2; 95% CI, 0.0 to 0.9). When the adjustment for Black race was omitted from the current eGFR equation, measured GFR in Blacks was underestimated (median, 7.1 ml per minute per 1.73 m2; 95% CI, 5.9 to 8.8). A new equation using age and sex and omitting race underestimated measured GFR in Blacks (median, 3.6 ml per minute per 1.73 m2; 95% CI, 1.8 to 5.5) and overestimated measured GFR in non-Blacks (median, 3.9 ml per minute per 1.73 m2; 95% CI, 3.4 to 4.4). For all equations, 85% or more of the eGFRs for Blacks and non-Blacks were within 30% of measured GFR. New creatinine-cystatin C equations without race were more accurate than new creatinine equations, with smaller differences between race groups. As compared with the current creatinine equation, the new creatinine equations, but not the new creatinine-cystatin C equations, increased population estimates of CKD prevalence among Blacks and yielded similar or lower prevalence among non-Blacks. CONCLUSIONS: New eGFR equations that incorporate creatinine and cystatin C but omit race are more accurate and led to smaller differences between Black participants and non-Black participants than new equations without race with either creatinine or cystatin C alone. (Funded by the National Institute of Diabetes and Digestive and Kidney Diseases.).

A multi-center retrospective cohort study defines the spectrum of kidney pathology in Coronavirus 2019 Disease (COVID-19).

Kidney failure is common in patients with Coronavirus Disease-19 (COVID-19), resulting in increased morbidity and mortality. In an international collaboration, 284 kidney biopsies were evaluated to improve understanding of kidney disease in COVID-19. Diagnoses were compared to five years of 63,575 native biopsies prior to the pandemic and 13,955 allograft biopsies to identify diseases that have increased in patients with COVID-19. Genotyping for APOL1 G1 and G2 alleles was performed in 107 African American and Hispanic patients. Immunohistochemistry for SARS-CoV-2 was utilized to assess direct viral infection in 273 cases along with clinical information at the time of biopsy. The leading indication for native biopsy was acute kidney injury (45.4%), followed by proteinuria with or without concurrent acute kidney injury (42.6%). There were more African American patients (44.6%) than patients of other ethnicities. The most common diagnosis in native biopsies was collapsing glomerulopathy (25.8%), which was associated with high-risk APOL1 genotypes in 91.7% of cases. Compared to the five-year biopsy database, the frequency of myoglobin cast nephropathy and proliferative glomerulonephritis with monoclonal IgG deposits was also increased in patients with COVID-19 (3.3% and 1.7%, respectively), while there was a reduced frequency of chronic conditions (including diabetes mellitus, IgA nephropathy, and arterionephrosclerosis) as the primary diagnosis. In transplants, the leading indication was acute kidney injury (86.4%), for which rejection was the predominant diagnosis (61.4%). Direct SARS-CoV-2 viral infection was not identified. Thus, our multi-center large case series identified kidney diseases that disproportionately affect patients with COVID-19 and demonstrated a high frequency of APOL1 high-risk genotypes within this group, with no evidence of direct viral infection within the kidney.

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.

Pseudo-anion gap metabolic acidosis from severe hypertriglyceridemia corrected by plasma exchange
.

BACKGROUND: Falsely low or even unmeasurable serum bicarbonate has been described in patients with severe hypertriglyceridemia or paraproteinemia. This phenomenon, known as pseudo-hypobicarbonatemia, is believed to be due to interference by these components when the commonly used enzymatic assay is utilized for serum bicarbonate measurement. The calculated bicarbonate derived from blood gas machines is not affected. This can lead to a misdiagnosis of a severe anion gap metabolic acidosis along with an extensive and expensive work-up. CASE PRESENTATIONS: We review a series of 5 patients with severe hypertriglyceridemia who presented with pseudo-hypobicarbonatemia and an elevated anion gap metabolic acidosis. Membrane-based therapeutic plasma exchange was utilized. RESULTS: Following aggressive lowering of the triglycerides, there was an immediate resolution of the pseudo-hypobicarbonatemia and anion gap metabolic acidosis. CONCLUSION: Recognition of lipemic serum in the setting of an otherwise unexplained anion gap metabolic acidosis should prompt the clinician to obtain a blood gas sample for true determination of the acid-base status. Doing so may avoid an extensive and expensive metabolic work-up.

The Glomerular Disease Study and Trial Consortium: A Grassroots Initiative to Foster Collaboration and Innovation.

Glomerular kidney disorders account for a significant proportion of chronic kidney disease and end-stage renal disease worldwide. Nevertheless, major obstacles make breakthrough progress in diagnosis and cure an ongoing challenge. Here we report the creation of a "grassroots" initiative that aims to provide new opportunities for nephrologists, pathologists, basic and clinical scientists, patients, and industry partners to collaborate in the field of glomerular kidney disease. Members of the medical community, including trainees, nephrologists, and nephropathologists, can participate in the open-access, Web-based, multidisciplinary clinical video case conferences, which provide "peer-to-peer" exchange of clinical and pathological expertise combined with a formal didactic curriculum. Participants can also join other aspects of the broader initiative. These include the participation in a multisite research study to facilitate enrollment of patients into a longitudinal clinical data and biorepository for glomerular kidney disorders. Items included in this prospective registry include the following: an ontology-based patient medical history, which is regularly updated; interval collection and storage of blood and urine samples; DNA collection; and a contact registry for patients who wish to participate in clinical trials. Participating sites and external scientists can leverage access to the database to pursue genetic, biomarker, epidemiological, and observational clinical effectiveness studies. Patients can independently sign up for a supplementary contact registry to participate in clinical trials if eligible. The broad spectrum of activities within this initiative will foster closer collaboration among trainees, practicing nephrologists, pathologists, and researchers, and may help to overcome some of the barriers to progress in the field of glomerular kidney disease.