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Critical Care (London, England) Apr 2022Preclinical models of acute kidney injury (AKI) consistently demonstrate that a uremic milieu enhances renal recovery and decreases kidney fibrosis. Similarly,... (Review)
Review
Preclinical models of acute kidney injury (AKI) consistently demonstrate that a uremic milieu enhances renal recovery and decreases kidney fibrosis. Similarly, significant decreases in monocyte/macrophage infiltration, complement levels, and other markers of inflammation in the injured kidney are observed across multiple studies and species. In essence, decreased renal clearance has the surprising and counterintuitive effect of being an effective treatment for AKI. In this Perspective, the author suggests a hypothesis describing why the uremic milieu is kidney protective and proposes a clinical trial of 'permissive azotemia' to improve renal recovery and long-term renal outcomes in critically ill patients with severe AKI.
Topics: Acute Kidney Injury; Azotemia; Female; Fibrosis; Humans; Kidney; Male; Social Planning
PubMed: 35484549
DOI: 10.1186/s13054-022-03988-0 -
Veterinary World Aug 2021Urethral obstruction (UO) is a common condition in feline medicine. Severe acid-base and electrolyte disorders promote relevant electrocardiographic changes in these...
BACKGROUND AND AIM
Urethral obstruction (UO) is a common condition in feline medicine. Severe acid-base and electrolyte disorders promote relevant electrocardiographic changes in these animals. Cardiac biomarkers such as cardiac troponin I have been shown to be useful in identifying cats with myocardial disease, but it has not been investigated whether UO leads to myocardial damages. This study aimed to evaluate biochemical changes, electrocardiographic findings, troponin I measurements, and electrolyte disturbances for 7 days in cats with UO.
MATERIALS AND METHODS
This follow-up prospective study included 33 cats diagnosed with UO for 7 days. For all cats, clinical examination, serum biochemistry, electrolyte analyses, blood pressure, and electrocardiography were performed. Cardiac troponin I was measured in the serum in 16 cats at 3 different times.
RESULTS
The mean age of the feline population was 1.83±1.58 years (mean±standard deviation). Creatinine, urea, blood urea nitrogen, glucose, phosphorus, base excess, bicarbonate, and serum potassium decreased significantly (p≤0.05), while ionic calcium and blood pH increased significantly (p≤0.05) at different times. Electrocardiographic abnormalities were observed in 21/33 (63.63%) of the felines on admission day. The electrocardiographic abnormalities were no longer observed on the subsequent days. Only one feline showed changes in troponin I cardiac concentrations.
CONCLUSION
This study suggests the sum and severity of electrolyte abnormalities aggravate the clinical and cardiovascular status of these patients. However, cTnI, blood pressure, and heart rate within the reference range do not exclude the presence of major cardiovascular and metabolic abnormalities. The hyperglycemia in felines with UO appears to be associated with decreased renal clearance, which may reflect the severity of hyperkalemia and azotemia. The metabolic and cardiovascular changes of these felines are minimized by the establishment of appropriate intensive care; however, cardiac and blood gas monitoring is essential to assess the severity of the disease.
PubMed: 34566314
DOI: 10.14202/vetworld.2021.2002-2008 -
Annals of Hepatology 2020Renal dysfunction is a common finding in cirrhotic patients and has a great physiologic, and therefore, prognostic relevance. The combination of liver disease and renal... (Review)
Review
Renal dysfunction is a common finding in cirrhotic patients and has a great physiologic, and therefore, prognostic relevance. The combination of liver disease and renal dysfunction can occur as a result of systemic conditions that affect both the liver and the kidney, although primary disorders of the liver complicated by renal dysfunction are much more common. As most of the renal dysfunction scenarios in cirrhotic patients correspond to either prerenal azotemia or hepatorenal syndrome (HRS), physicians tend to conceive renal dysfunction in cirrhotic patients as mainly HRS. However, there are many systemic conditions that may cause both a "baseline" chronic kidney damage and a superimposed kidney dysfunction when this systemic condition worsens. The main aim of this article is to review some of the most important non prerenal non-HRS considerations regarding acute on chronic kidney dysfunction in cirrhotic patients, including renal manifestation of related to non-alcoholic steatohepatitis (NASH) viral hepatitis, the effect of cardiorenal syndrome in cirrhotics and corticosteroid-deficiency associated renal dysfunction.
Topics: Acute Kidney Injury; Adrenal Cortex Hormones; Cardio-Renal Syndrome; Hepatitis, Viral, Human; Humans; Liver Cirrhosis; Non-alcoholic Fatty Liver Disease; Renal Insufficiency, Chronic
PubMed: 31594758
DOI: 10.1016/j.aohep.2019.06.022 -
Sovremennye Tekhnologii V Meditsine 2021was to study the species composition of colon microbiocenosis in patients with chronic kidney disease receiving programmed hemodialysis treatment and to evaluate the...
UNLABELLED
was to study the species composition of colon microbiocenosis in patients with chronic kidney disease receiving programmed hemodialysis treatment and to evaluate the efficacy of its correction using a new immobilized synbiotic.
MATERIALS AND METHODS
Samples of colon microbiota from 62 patients undergoing programmed hemodialysis were studied before and after a course of diet therapy that included probiotic components, in particular, the immobilized synbiotic LB-complex L. Isolation of microorganisms was carried out according to our original method; for bacteria identification, a MALDI-TOF Autoflex speed mass spectrometer (Bruker Daltonik, Germany) was used in the Biotyper program mode. The results were assessed using the criteria proposed by the authors and based on the OST 91500.11.0004-2003. The efficacy of the immobilized synbiotic was determined based on the clinical data, questionnaires, and bacteriological tests.
RESULTS
In patients receiving programmed hemodialysis (before the start of the diet therapy), chronic moderate inflammation and azotemia were found. Dysbiotic changes in microbiocenosis were revealed in all the examined patients; in the absence or suppression of lacto- and bifidoflora, the number and diversity of , , , and other bacteria increased, which was consistent with the theory of functional redundancy of gut microbiota. From the answers to the questionnaires, a decrease in the quality of life was found (up to 70 points out of 100) according to six of the eight scales used. After the combined therapy using the synbiotic LB-complex L in the study group, 56% of the examined patients showed their microbiocenosis restored to normal; no grade III dysbiosis was detected in any patient. There was a significant decrease in CRP and ESR in these patients and an improvement in the quality of life by criteria reflecting physical health.
CONCLUSION
In patients receiving programmed hemodialysis, the addition of a probiotic component in the diet therapy restores the evolutionarily determined structure of the microbiocenosis, normalizes its functions, and leads to an overall improvement in health and quality of life.
Topics: Colon; Dysbiosis; Humans; Quality of Life; Renal Dialysis; Synbiotics
PubMed: 34796006
DOI: 10.17691/stm2020.12.5.07 -
Journal of the American Veterinary... Feb 2020To evaluate the utility of commercially available reagent test strips for estimation of BUN concentration and detection of azotemia in pet rabbits () and ferrets ().
OBJECTIVE
To evaluate the utility of commercially available reagent test strips for estimation of BUN concentration and detection of azotemia in pet rabbits () and ferrets ().
SAMPLE
65 blood samples from 53 rabbits and 71 blood samples from 50 ferrets of various health statuses.
PROCEDURES
BUN concentrations were measured with a clinical laboratory biochemical analyzer and estimated with a reagent test strip. Results obtained with both methods were assigned to a BUN category (range, 1 to 4; higher categories corresponded to higher BUN concentrations). Samples with a biochemical analyzer BUN concentration ≥ 27 mg/dL (rabbits) or ≥ 41 mg/dL (ferrets) were considered azotemic. A test strip BUN category of 3 or 4 (rabbits) or 4 (ferrets) was considered positive for azotemia.
RESULTS
Test strip and biochemical analyzer BUN categories were concordant for 46 of 65 (71%) rabbit blood samples and 58 of 71 (82%) ferret blood samples. Sensitivity, specificity, and accuracy of the test strips for detection of azotemia were 92%, 79%, and 82%, respectively, for rabbit blood samples and 80%, 100%, and 96%, respectively, for ferret blood samples.
CONCLUSIONS AND CLINICAL RELEVANCE
Test strips provided reasonable estimates of BUN concentration but, for rabbits, were more appropriate for ruling out than for ruling in azotemia because of false-positive test strip results. False-negative test strip results for azotemia were more of a concern for ferrets than rabbits. Testing with a biochemical analyzer remains the gold standard for measurement of BUN concentration and detection of azotemia in rabbits and ferrets.
Topics: Animals; Azotemia; Blood Urea Nitrogen; Ferrets; Rabbits; Reagent Strips; Urea
PubMed: 31999516
DOI: 10.2460/javma.256.4.449 -
American Journal of Physiology.... Nov 2020Severe acute pancreatitis (SAP) includes persistent systemic inflammation (SIRS) and multiorgan failure (MOF). The mechanism of transition from SIRS to MOF is unclear....
Severe acute pancreatitis (SAP) includes persistent systemic inflammation (SIRS) and multiorgan failure (MOF). The mechanism of transition from SIRS to MOF is unclear. We developed a fluid compartment model and used clinical data to test predictions. The model includes vascular, interstitial and "third-space" compartments with variable permeability of plasma proteins at the capillaries. Consented patients from University of Pittsburgh Medical Center Presbyterian Hospital were studied. Preadmission and daily hematocrit (HCT), blood urea nitrogen (BUN), creatine (Cr), albumin (Alb), and total protein (TP) were collected, and nonalbumin plasma protein (NAPP = TP minus the Alb) was calculated. Subjects served as their own controls for trajectory analysis. Of 57 SAP subjects, 18 developed MOF (5 died), and 39 were non-MOF (0 died). Compared with preadmission levels, admission HCT increased in MOF +5.00 [25%-75% interquartile range, IQR] versus non-MOF -0.10 [-1.55, 1.40] ( < 0.002) with HCT > +3 distinguishing MOF from non-MOF (odds ratio 17.7, = 0.014). Preadmission Alb fell faster in MOF than non-MOF ( < 0.01). By , TP and NAPP dropped in MOF but not non-MOF ( < 0.001). BUN and Cr levels increased in MOF ( = 0.001), but BUN-to-Cr ratios remained constant. Pancreatic necrosis was more common in MOF (56%) than non-MOF (23%). Changing capillary permeability to allow loss of NAPP in this model predicts loss of plasma oncotic pressure and reduced vascular volume, hypotension with prerenal azotemia and acute kidney dysfunction, pancreas necrosis, and pulmonary edema from capillary leak in the lung with acute respiratory distress syndrome. Sequential biomarker analysis in humans with or without MOF is consistent with this model. This study is registered on https://clinicaltrials.gov at NCT03075605. Acute pancreatitis is a sudden inflammatory response to pancreatic injury that may spread to systemic inflammation, multiorgan failure, and death in some patients. With the use of the predictions of a new mechanistic model, we compared patients with severe acute pancreatitis with or without multiorgan failure. All biomarkers of capillary leak and clinical features of multiorgan failure were accurately predicted. This provides a new paradigm for understanding and developing new treatments for patients with severe acute pancreatitis.
Topics: Acute Disease; Adult; Aged; Blood Proteins; Blood Urea Nitrogen; Body Fluid Compartments; Capillary Leak Syndrome; Capillary Permeability; Female; Hematocrit; Humans; Hypotension; Hypovolemia; Male; Middle Aged; Models, Biological; Multiple Organ Failure; Necrosis; Pancreatitis; Serum Albumin; Systemic Inflammatory Response Syndrome
PubMed: 32877220
DOI: 10.1152/ajpgi.00285.2020 -
Cells Apr 2021Canonical transient receptor potential 6 (TRPC6) channels have been implicated in familial and acquired forms of focal and segmental glomerulosclerosis (FSGS) in...
Canonical transient receptor potential 6 (TRPC6) channels have been implicated in familial and acquired forms of focal and segmental glomerulosclerosis (FSGS) in patients and animal models, as well as in renal fibrosis following ureteral obstruction in mice. Aging also evokes declines in renal function owing to effects on almost every renal compartment in humans and rodents. Here, we have examined the role of TRPC6 in driving inflammation and fibrosis during aging in Sprague-Dawley rats. This was assessed in rats with non-functional TRPC6 channels owing to CRISPR-Cas9 deletion of a portion of the ankyrin repeat domain required for the assembly of functional TRPC6 channels ( rats). Wild-type littermates ( rats) were used as controls. Animals were evaluated at 2 months and 12 months of age. There was no sign of kidney disease at 2 months of age, regardless of genotype. However, by 12 months of age, all rats examined showed declines in renal function associated with albuminuria, azotemia and increased urine excretion of β2-microglobulin, a marker for proximal tubule pathology. These changes were equally severe in and rats. We also observed age-related increases in renal cortical expression of markers of fibrosis (α-smooth muscle actin and vimentin) and inflammation (NLRP3 and pro-IL-1β), and there was no detectable protective effect of TRPC6 inactivation. Tubulointerstitial fibrosis assessed from histology also appeared equally severe in and rats. By contrast, glomerular pathology, blindly scored from histological sections, suggested a significant protective effect of TRPC6 inactivation, but only within the glomerular compartment.
Topics: Aging; Animals; Biomarkers; Fibrosis; Glomerulosclerosis, Focal Segmental; Inflammation; Kidney; Rats; TRPC6 Cation Channel
PubMed: 33918778
DOI: 10.3390/cells10040856 -
Journal of Feline Medicine and Surgery Feb 2021Meloxicam therapy may benefit cats with degenerative joint disease, and retrospective studies suggest it could slow kidney disease progression and increase survival....
OBJECTIVES
Meloxicam therapy may benefit cats with degenerative joint disease, and retrospective studies suggest it could slow kidney disease progression and increase survival. This study aimed to prospectively evaluate the renal effects of low-dose meloxicam treatment (0.02 mg/kg/day) over 6 months in cats with chronic kidney disease (CKD).
METHODS
Twenty-one cats with stable International Renal Interest Society stage 2 or 3 CKD were recruited and randomized to placebo or meloxicam groups. Cats were evaluated at baseline and at 1, 3 and 6 months, including blood pressure, chemistry, symmetric dimethylarginine (SDMA), glomerular filtration rate (GFR), urinalysis, urine protein:creatinine ratio (UPC), urine transforming growth factor-beta (β):creatinine ratio, urine clusterin, urine cystatin B and serum inosine.
RESULTS
No statistical difference was observed in systolic blood pressure, blood urea nitrogen, creatinine, SDMA, GFR, urine transforming growth factor-β:creatinine ratio, urine clusterin, urine cystatin B or serum inosine in cats receiving meloxicam vs placebo. Mean UPC was greater in the meloxicam group (0.33) than the placebo group (0.1) at 6 months ( = 0.006). Four cats had meloxicam discontinued owing to potential (mainly gastrointestinal) adverse effects.
CONCLUSIONS AND RELEVANCE
No decline in renal excretory function was observed when meloxicam was administered to cats with CKD. However, gastrointestinal adverse effects were observed, and cats that received meloxicam had greater proteinuria at 6 months than cats that received placebo. As proteinuria is associated with negative outcomes (progression of azotemia and hypertension) in cats with CKD, this finding suggests that meloxicam should be used with caution in cats with CKD and UPC monitored. Until further research is available, clinicians should weigh the risk of potential increased proteinuria against quality of life benefits when considering meloxicam for analgesia in cats with renal disease.
Topics: Animals; Cat Diseases; Cats; Glomerular Filtration Rate; Meloxicam; Quality of Life; Renal Insufficiency, Chronic; Retrospective Studies
PubMed: 32594827
DOI: 10.1177/1098612X20935750 -
Journal of Veterinary Internal Medicine Sep 2020Focal segmental glomerulosclerosis (FSGS) is a common cause of nonimmune complex glomerulopathy and the prognosis and clinicopathologic findings associated with this...
BACKGROUND
Focal segmental glomerulosclerosis (FSGS) is a common cause of nonimmune complex glomerulopathy and the prognosis and clinicopathologic findings associated with this condition have not been described in dogs.
OBJECTIVE
To characterize the presentation and identify clinical factors associated with the survival of dogs with FSGS.
ANIMALS
Seventy-seven dogs diagnosed with FSGS based on evaluation of renal biopsy samples submitted to the International Veterinary Renal Pathology Service.
METHODS
Retrospective review of medical records of dogs biopsied for evaluation of proteinuria between January 2015 and May 2017.
RESULTS
The incidence of FSGS among all dogs biopsied for proteinuria was 26%. Significantly more females (48; 62.3%) than males (29; 37.7%) were affected (P = .04). At the time of biopsy, median serum creatinine concentration (SCr) was 1.2 mg/dL (range, 0.3-8.7), median serum albumin concentration (Alb) was 2.8 g/dL (range, 1.1-4.6), median systolic blood pressure was 153.5 mm Hg (range, 95-260), and median urine protein : creatinine ratio was 5.9 (range, 1.4-22). Median survival time after biopsy was 258 days (range, 26-1003) for dogs that died from all causes (n = 32). Factors that were associated with a shorter survival time included SCr ≥ 2.1 mg/dL (P < .01) and Alb < 2 g/dL (P < .01).
CONCLUSIONS AND CLINICAL IMPORTANCE
Most dogs with FSGS were female, and although commonly hypertensive, azotemia, severe hypoalbuminemia and ascites or edema were observed infrequently. Variables significantly associated with survival time were SCr and Alb.
Topics: Animals; Biopsy; Dog Diseases; Dogs; Female; Glomerulosclerosis, Focal Segmental; Kidney; Kidney Diseases; Male; Prognosis; Proteinuria; Retrospective Studies
PubMed: 33463760
DOI: 10.1111/jvim.15837 -
Journal of Feline Medicine and Surgery Oct 2022The aims of this study were to evaluate serum symmetric dimethylarginine (SDMA) and creatinine concentrations in cats with urethral obstruction pre- and...
OBJECTIVES
The aims of this study were to evaluate serum symmetric dimethylarginine (SDMA) and creatinine concentrations in cats with urethral obstruction pre- and post-decompression of the obstruction, and to determine if pre-decompression values were predictive of post-decompression renal function, as measured by SDMA and creatinine.
METHODS
This was a prospective observational study. Twenty-five client-owned cats with urethral obstruction were hospitalized for decompression of the obstruction. Serum SDMA and creatinine were prospectively assessed at presentation, 24 h post-decompression and 5-20 days post-decompression. Urinalysis and culture were assessed at presentation and at the final follow-up. Exclusion criteria included positive urine culture, reobstruction or failure to obtain required samples.
RESULTS
Mean SDMA concentration dropped by 41.8% from an initial pre-decompression concentration of 17.6 µg/dl to 10.3 µg/dl 24 h post-decompression ( <0.001). The mean creatinine value dropped by 38.4% from an initial pre-decompression concentration of 2.5 mg/dl to 1.5 mg/dl 24 h post-decompression ( <0.001). There was no association between SDMA concentration at initial presentation and SDMA concentration 5-20 days after urethral catheterization (Spearman's ρ = 0.205, = 0.314). Creatinine concentration upon initial presentation was associated with the 5-20 day values after urethral catheterization (Spearman's ρ = 0.583, <0.002). Twenty percent of cases were excluded due to bacterial growth on initial urine culture. SDMA and creatinine concentrations were significantly higher in these cases (median 59 µg/dl and 10.9 mg/dl, respectively) compared with those with negative cultures (median 14 µg/dl and 1.6 mg/dl [ <0.002 and <0.001], respectively).
CONCLUSIONS AND RELEVANCE
Both SDMA and creatinine decreased significantly after urethral catheterization, suggesting that renal function post-decompression cannot be predicted by the pre-decompression concentrations of these values.
Topics: Animals; Arginine; Biomarkers; Cat Diseases; Cats; Creatinine; Renal Insufficiency, Chronic; Urethral Obstruction
PubMed: 34894831
DOI: 10.1177/1098612X211060677