Fractional electrolyte excretion and osmolality in the early diagnosis of acute kidney injury in cats with urethral obstruction

Acute Kidney Injury (AKI) can be defined as a spectrum of diseases associated with a sudden onset of a renal failure status, the feline patient has azotemia, the disorder in fractional electrolyte excretion (FE), and shedding of epithelial cells from renal tubular segments observed in the urinary sediment. Thus, the objective of the present study was to evaluate the FE, plasma and urinary osmolality, and urinary specific gravity (USG) in cats that spontaneously developed AKI due to urethral obstruction (UO) and healthy cats. Blood and urine samples were collected from a group of 20 cats diagnosed with AKI secondary to urethral obstruction (GAKI; n=20) and clinically healthy cats (GC; n=15). The serum creatinine (sCre) and urinary creatinine (uCre), were measured by spectrophotometry, serum and urinary analyzes of sodium, potassium and chloride by ion selective electrode device and serum and urinary osmolarity by osmometer. The GAKI results were statistically compared with those of the CG using Student's t tests to assess normal data, while the Maan-Whitney test was used for non-normal data. A significant increase in the sCr, sK, FENa, FECl and RFI parameters of the GAKI cats when compared to the GC (p < 0.05). The sCl, USG, uCr, uK and uOSM parameters decreased significantly when compared between the two groups. Thus, given the established methodology and the results found, it is possible to infer that an increase in EFNa, EFCl in addition to the RFI and a decrease in USG and uOSM were associated with cats with AKI and can serve as markers of kidney damage, as well as monitoring the prognosis.

Acute and Chronic Posterior Pituitary Insufficiency Among Traumatic Brain Injury Patients at a Tertiary Care Center

Background: Traumatic brain injury (TBI) is the leading cause of death and disability in young adults. Disorders of salt and water balance are the most commonly recognized medical complications in the immediate post-TBI period and contribute to early morbidity and mortality. Objective: We aimed to evaluate the prevalence of acute (during hospital stay) and chronic posterior pituitary dysfunction in patients of head injury admitted at our tertiary care hospital. Study Design: Prospective, Observational study. Participants: 136 patients, attending tertiary care in North India with TBI with radiological evidence of head injury. Methodology: The severity of brain injury was assessed by the Glasgow Coma Scale (GCS), and Modified Rankin Scale (MRS) score at the time of admission. Lab measurements, apart from routine CBC and biochemical tests, included tests of serum and urinary osmolality, serum sodium, cortisol, and thyroid function test during the hospital stay. All patients were monitored closely during the hospital stay. Surviving patients were evaluated at 3, 6, and 12 months of follow-up. Urinary output and water deprivation tests were done to determine chronic posterior pituitary dysfunction. The results were compared against normative data obtained from 25 matched, healthy controls. Serum & urinary osmolality was measure by the freezing point method. Diabetes insipidus (DI) and Syndrome of inappropriate ADH secretion (SIADH) were diagnosed according to standard criteria. Results: Of 136 patients admitted, 61 (44.85%) had a mild head injury (GCS, ≤8), 47 (35.55%) had a moderate injury (GCS, 9-12), and 27 (19.85%) had a severe injury (GCS, 13-15). DI occurred in 10 patients (7.4%), while SIADH was observed in 4 patients in the immediate TBI period. Risk factors for diabetes insipidus were GCS of ≤ 8 at admission, midline shift, and surgical intervention. DI was an independent risk factor for death. There was a negative correlation between the presence of DI and GCS score (r, -0.367). Most of the patients with DI (8 out of 10) died during the hospital stay. One patient persisted to have partial diabetes insipidus and another one SIADH at three months post-TBI; both patients had recovered at six months of follow-up. No new case of DI or SIADH occurred on the follow up to 12 months. Conclusion: The incidence of acute DI in severe head injury (GCS ≤ 8) could be an indicator of the severity of TBI, and associated with increased mortality as most of our patients died during the hospital stay.

MO130GLOMERULAR FILTRATION RATE IS THE MAIN PREDICTOR OF URINE OUTPUT IN AUTOSOMAL DOMINANT POLYCYSTIC KIDNEY DISEASE (ADPKD) PATIENTS TREATED WITH TOLVAPTAN

Background and Aims Tolvaptan was approved to treat autosomal dominant polycystic kidney disease (ADPKD) to slow the rate of kidney growth and renal function decline. Tolvaptan blocks the V2 vasopressin receptor in renal collecting ducts and distal nephron causing intense polyuria. Few authors have analyzed what factors influence the volume of diuresis in patients taking tolvaptan. Method We have analyzed the influence of solute excretion and glomerular filtration rate, besides age and gender as predictors of urine output, using multivariable analysis. In concret, we have searched the importance of osmolar excretion as predictor of volume of diuresis. Results We studied 24 h-urine samples from 18 ADPKD patients on treatment with tolvaptan, who had received the three doses: 45/15, 60/30 and 90/30 mg. Each patient was represented once per dose, for a total of 54 urine samples (Table 1). Tolvaptan increased urine volume, which was roughly doubled, and roughly halved urine solute concentrations expressed by volume and calculated osmolality. By contrast, solute concentrations expressed as ratios with creatinine remained constant as did osmolality corrected with urinary creatinine, indicating that there was no change in solute excretion after tolvaptan. Urine volume was correlated with serum creatinine (Rho= -0.36, p= 0.008), urinary creatinine (Rho = -0.29, p = 0.034) and GFR-MDRD4 (Rho = 0.44, p= 0.001). Urine volume was correlated with calculated daily osmolar excretion in Osm/day (Rho = 0.76, p &lt;0.001). Urine volume was not correlated with calculated urinary osmolality in mOsm/Kg (Rho= -0.04, p= 0.77) or as urinary osmolality/creatinine ratio (Rho= 0.23, p= 0.1). Correlation of urine volume with osmolar excretion was lost when urine volume was removed from the predictor variable. Urine volume was additionally not correlated with urinary urea o sodium concentrations nor their solute/creatinine ratios, and although it was correlated with urinary potassium concentration (Rho = -0.33, p=0.014), it was not correlated with potassium/creatinine ratio. We also performed a linear regression analysis searching predictors of urine volume. Only GFR and the osmolality/creatinine ratio were significant predictors of urine volume (urine volume= 55.35 x GFR + 4.74 x Osmolality/Cr; r2= 0.41, p&lt;0.001) but individual solute assessments or tolvaptan dose did not predict urine volume. Conclusions Therefore, urine volume after initiating tolvaptan in patients with ADPKD is influenced mainly by the degree of renal function. There might also be a contribution of urinary solute load but it can not be studied using total solute excretion due to collinearity. We propose that the urinary solute/creatinine ratio and osmolality/creatinine ratio should be used to search for predictors of urine output in patients on tolvaptan.

A metabolically stable apelin-17 analog decreases AVP-induced antidiuresis and improves hyponatremia

Apelin and arginine-vasopressin (AVP) are conversely regulated by osmotic stimuli. We therefore hypothesized that activating the apelin receptor (apelin-R) with LIT01-196, a metabolically stable apelin-17 analog, may be beneficial for treating the Syndrome of Inappropriate Antidiuresis, in which AVP hypersecretion leads to hyponatremia. We show that LIT01-196, which behaves as a potent full agonist for the apelin-R, has an in vivo half-life of 156 minutes in the bloodstream after subcutaneous administration in control rats. In collecting ducts, LIT01-196 decreases dDAVP-induced cAMP production and apical cell surface expression of phosphorylated aquaporin 2 via AVP type 2 receptors, leading to an increase in aqueous diuresis. In a rat experimental model of AVP-induced hyponatremia, LIT01-196 subcutaneously administered blocks the antidiuretic effect of AVP and the AVP-induced increase in urinary osmolality and induces a progressive improvement of hyponatremia. Our data suggest that apelin-R activation constitutes an original approach for hyponatremia treatment.

The role of fractional excretion of sodium and urinary osmolality in Acute Kidney Injury in liver transplant

Objective We analysed urinary osmolality and the fractional excretion of sodium (FeNa) in the perioperative period of liver transplant (LT) and their association with on renal impairment, dialysis and mortality. Methods We aimed to determine the pattern of elevation of urinary (U) osmolality and FeNa levels in the perioperative period of liver transplant and how these are associated with the development of acute kidney injury (AKI) according to the Kidney Disease Improving Global Outcomes- (KDIGO) criteria, AKI severity, differential diagnosis in acute tubular necrosis (ATN), need for renal replacement therapy (RRT) and mortality. We assessed the biomarkers in the perioperative period: pre-operative, after portal reperfusion (APR), and at 6, 18, 24 and 48 hours after LT. Results Of the 100 enrolled patients, 87 developed AKI in the first week after LT, with 59 considered KDIGO stages 2 and 3 as defined by severe AKI and 75 defined as ATN; 34 were dialyzed, and 21 died within 60 days after LT. The FeNa was also useful for differential diagnosis in ATN, but the values remained below 1%, with an increased median in poor outcomes: severe AKI, ATN, need-RRT and non-survival. For predicting need-RRT, FeNa achieved an AUC of 0,78 (CI 0,66–0,90). The APR U osmolality measurement showed differences in all outcomes (with p < 0,05), and high osmolality was revealed to be a renal protective factor and found to predict need for RRT and mortality with AUCs of 0,11 (CI 0,02–0,20) and 0,21 (CI 0,07–0,34), respectively. Conclusion The increase in FeNa reveals a loss of Na secretion capacity and even in liver disease patients it has been shown a tool that aided the differential diagnosis if the cutoff value was adjusted. Osmolarity demonstrated the maintenance of urine concentration capacity by nephrons. More large studies should confirm these results.