Blood pressure in hyperthyroid cats before and after radioiodine treatment.

BACKGROUND: Hyperthyroid cats commonly have systemic hypertension, with a reported prevalence of 7% to 48%. Although hypertension might be expected to resolve once treatment restores euthyroidism, it can persist or only first develop after treatment. OBJECTIVES: To determine the proportion of hyperthyroid cats with hypertension (systolic blood pressure [SBP] ≥160 mm Hg), persistence or first development of hypertension after successful radioiodine treatment, and correlation of post-treatment hypertension with azotemia or hypothyroidism. ANIMALS: Four hundred one hyperthyroid nonazotemic cats were included in the study. METHODS: Prospective, cross-sectional and before-and-after studies. All hyperthyroid cats had SBP measured by Doppler; 255 had SBP rechecked 6 months after successful radioiodine (131I) treatment. RESULTS: Of untreated hyperthyroid cats, 108/401 (27%) were hypertensive. A higher proportion of hypertensive cats were nervous/excited compared with normotensive cats (47% vs 12%; P < .001). Of the initially hypertensive cats, 87/108 cats were reexamined after 131I treatment; 43/87 (49%) cats normalized SBP, whereas 44/87 (51%) remained hypertensive. Of the initially normotensive cats, 16/168 (9.5%) first developed hypertension after successful 131I treatment. 7/60 (12%) of the 131I-treated hypertensive cats were azotemic and 9/60 (15%) were hypothyroid. A higher proportion of cats remaining hypertensive had nervous/excited demeanor than did normotensive cats (50% vs 17%; P < .001). CONCLUSIONS/CLINICAL IMPORTANCE: Hypertension, when present, resolves in many hyperthyroid cats after successful treatment. Hyperthyroid cats uncommonly develop new hypertension after treatment. Persistent or newly detected hypertension was unrelated to azotemia or iatrogenic hypothyroidism. More frequently perceived nervousness/anxiety in radioiodine-treated hypertensive cats suggests that many of these cats might have "situational" hypertension, as hyperthyroid-induced hypertension should resolve after treatment.

The impact of preoperative kidney replacement therapy on kidney outcome and survival in patients with left ventricular assist device.

Left ventricular assist device (LVAD) has been highlighted as a new treatment option in the end-stage heart failure (HF). Kidney outcome after LVAD in severe cardiorenal syndrome (CRS) patients requiring kidney replacement therapy (KRT) is unclear. We investigated the impact of preoperative KRT on kidney function and survival in LVAD patients with severe CRS. A total of 50 patients followed up for at least 1 year after LVAD implantation was analyzed. The primary outcomes were estimated glomerular filtration rate and survival rate. Patients were divided into two groups depending on in-hospital KRT before LVAD implantation: the control group (n = 33) and the KRT group (n = 17). Postoperative KRT was performed for 76.5% of patients in the KRT group, and all of them discontinued KRT before discharge. There were no statistically significant differences in the degree of eGFR decline in survivors according to preoperative KRT. Although there were no statistically significant differences in the degree of eGFR decline in survivors regardless of preoperative KRT, old age (ß -0.94, p < 0.01), preexisting chronic kidney disease (ß -21.89, p < 0.01), and high serum creatinine (ß -13.95, p < 0.01) were identified as independent predictors of post-LVAD eGFR decline. Mortality rate was higher, and more patients progressed to end-stage kidney disease in KRT group than control group. However, LVAD still can be considered as the treatment option in end-stage HF patients with severe CRS requiring KRT, especially in those with young age and previous normal kidney function.

Low-Flow Acute Kidney Injury: The Pathophysiology of Prerenal Azotemia, Abdominal Compartment Syndrome, and Obstructive Uropathy.

AKI is a syndrome, not a disease. It results from many different primary and/or secondary etiologies and is often multifactorial, especially in the hospitalized patient. This review discusses the pathophysiology of three etiologies that cause AKI, those being kidney hypoperfusion, abdominal compartment syndrome, and urinary tract obstruction. The pathophysiology of these three causes of AKI differs but is overlapping. They all lead to a low urine flow rate and low urine sodium initially. In all three cases, with early recognition and correction of the underlying process, the resulting functional AKI can be rapidly reversed. However, with continued duration and/or increased severity, cell injury occurs within the kidney, resulting in structural AKI and a longer and more severe disease state with increased morbidity and mortality. This is why early recognition and reversal are critical.

Evaluation of the progression of non-azotemic proteinuric chronic kidney disease in dogs.

Proteinuria is a recognized risk factor for progression of canine chronic kidney disease (CKD). However, the prognosis of non-azotemic proteinuric CKD in dogs has been studied only to a limited extent. Moreover, the degree to which proteinuria should be decreased to delay CKD progression remains unknown. The purposes of this study were (1) to identify factors associated with disease progression and (2) to investigate the degree of proteinuria, albuminuria, and blood pressure during the course of treatment associated with the progression using time-averaged urine protein:creatinine ratio (UPC) and urine albumin:creatinine ratio (UAC) in canine non-azotemic proteinuric CKD. Twenty-one dogs with non-azotemic proteinuric CKD were included in the study. High UPC and UAC were associated with CKD progression (P < .05). Time-averaged high UPC and UAC were significantly related to progression (P < .05). The cutoff values of these time-averaged parameters for predicting the progression were 4.1 and 2.0, respectively. In dogs with non-azotemic proteinuric CKD, more severe proteinuria and albuminuria were associated with progression. The present study suggests that because UPC ≥ 4.1 and UAC ≥ 2.0 during treatment were associated with a faster progression of non-azotemic proteinuric CKD, therapeutic intervention is warranted.

Non-diabetic glycosuria as a diagnostic clue for acute tubulointerstitial nephritis in patients with azotemia.

BACKGROUND: Glycosuria is one of the manifestations of acute tubulointerstitial nephritis (ATIN), but may also be observed in other renal diseases. In this study, we investigated the value of non-diabetic glycosuria as a diagnostic clue for ATIN. METHODS: We retrospectively reviewed the medical records of adult patients who underwent a kidney biopsy as an evaluation for serum creatinine > 1.4 mg/dL. Patients with proteinuria in the nephrotic range, diabetes mellitus, or transplanted kidney were excluded. The laboratory abnormalities suggestive of tubular injury were compared between 28 patients (14 men and 14 women, mean age 48.5 ± 14.1 years) with ATIN and 116 patients (76 men and 40 women, mean age 53.1 ± 15.0 years) with other diagnoses. RESULTS: In ATIN, glycosuria (≥ 1+ on dipstick; 68%) was more frequent than hypophosphatemia (18%), hypouricemia (18%), hypokalemia (18%), and tubular proteinuria (40%). In other diagnoses, glycosuria (≥ 1+) was detected in 7 (6%) patients; 6 of them had the histological diagnosis of antineutrophil cytoplasmic antibody-associated glomerulonephritis. The presence of glycosuria (≥ 1+) had 68% sensitivity and 94% specificity for ATIN, with the positive likelihood ratio of 11.24 and the negative likelihood ratio of 0.34. Pyuria and low total CO2 were equally and more sensitive (68% and 71%, respectively) than glycosuria (≥ 1+), but had no diagnostic value due to low specificities (58% and 60%, respectively). CONCLUSION: In non-diabetic, non-nephrotic patients undergoing a kidney biopsy for azotemia, 1+ or higher glycosuria, if present, was a good predictor of the diagnosis of ATIN.

Clinicopathological characteristics of light chain proximal tubulopathy in Korean patients and the diagnostic usefulness of immunohistochemical staining for immunoglobulin light chain.

BACKGROUND: Light chain proximal tubulopathy (LCPT) is a rare paraproteinemic renal disease that has been mostly reported in Western patients. LCPT is characterized by the accumulation of immunoglobulin (Ig)-light chain (LC) in the proximal tubule. Immunohistochemical staining for Ig-LC has not been investigated in the context of LCPT. We reported the clinicopathological characteristics and Ig-LC immunoexpression of patients with LCPT for the first time in Korea. METHODS: We reviewed the clinicopathological findings of 5 Korean patients diagnosed with LCPT between 2016 and 2018. In addition, immunohistochemical staining for κ-LC and λ-LC was conducted on paraffin-embedded tissues. RESULTS: The median age was 63 years, and the male-to-female ratio was 3:2. The primary renal manifestations were either azotemia or tubular proteinuria. All patients were diagnosed with multiple myeloma with monoclonal κ-LC (#1-2) or λ-LC (#3-5) in the serum and urine. Kidney biopsies revealed diverse and subtle alterations of the proximal tubule, including crystallization, vacuolization, and/or swelling. Electron microscopy revealed crystals in patients #1-2 and non-crystalline particles within numerous/large/dysmorphic lysosomes in patients #3-5. Ig-LC restriction was demonstrated in the proximal tubule as κ-type in patients #1-2 and as λ-type in patients #3-5 by immunohistochemistry and immunofluorescence. Immunohistochemical staining showed diffuse positivity to κ- and λ-LC, although immunofluorescent staining for κ-LC was focal and weak. LCPT has diverse clinicopathological characteristics and subtle morphological alterations, which necessitate ancillary tests for diagnosis. CONCLUSIONS: We introduced immunohistochemical staining for Ig-LC as a useful tool for the diagnosis of LCPT, especially in the case of κ-type crystals.

Symmetric dimethylarginine in hyperthyroid cats before and after treatment with radioactive iodine.

OBJECTIVES: The purpose of this study was to evaluate symmetric dimethylarginine (SDMA) in hyperthyroid cats before and after treatment with radioactive iodine and to determine how pretreatment SDMA relates to the development of post-treatment azotemia. METHODS: Eighty-four non-azotemic hyperthyroid cats had serum SDMA and creatinine evaluated before and 1, 3 and 6 months after treatment with radioiodine therapy. RESULTS: Baseline SDMA was increased in 7% (n = 6/84) of cats, whereas SDMA was increased in 19% (n = 15/81), 20% (n = 16/80) and 32% (n = 26/81) at 1 month, 3 months and 6 months after treatment, respectively. Creatinine was not elevated in any of the cats at baseline because of the study design, and was elevated in 6% (n = 5/81), 15% (n = 12/80) and 15% (n = 12/81) of cats at 1, 3 and 6 months after treatment, respectively. SDMA (median 11 µg/dl, range 1-22 µg/dl) was significantly higher at 3 (12 µg/dl, range 6-45 µg/dl; P = 0.005) and 6 months (11 µg/dl, 6-25 µg/dl; P <0.001) compared with baseline (11 µg /dl, range 1-21 µg/dl). The median baseline SDMA was significantly higher in the azotemic group (13 µg/dl, range 11-22 µg/dl) compared with the non-azotemic group (10 µg/dl, range 1-21 µg/dl, P = 0.002). The sensitivity of SDMA for detecting azotemia after treatment was 15.4%, with a specificity of 94.4%. Baseline serum SDMA concentration had a moderately positive association with baseline creatinine concentration (P <0.001, r = 0.437). At 6 months, there was a strong positive correlation between SDMA and creatinine concentrations (P <0.001, r = 0.721). There was no significant correlation with SDMA and thyroxine at baseline (P = 0.772, r = -0.034) or 6 months (P = 0.492, r = -0.078). CONCLUSIONS AND RELEVANCE: SDMA increases in cats treated for hyperthyroidism with radioactive iodine and likely reflects associated changes in glomerular filtration rate. An increased SDMA concentration above the reference interval prior to treatment has a high specificity but poor sensitivity for the prediction of post-treatment azotemia.

Prevalence of iatrogenic hypothyroidism in hyperthyroid cats treated with radioiodine using an individualised scoring system.

OBJECTIVES: The aim of this study was to report the prevalence of iatrogenic hypothyroidism, with or without azotaemia, based on the measurement of serum total thyroxine (T4), thyroid-stimulating hormone (TSH) and creatinine concentrations, in hyperthyroid cats undergoing radioiodine (131I) treatment where the 131I dose was calculated using a previously described scoring system. A secondary aim of the study was to determine the positive and negative predictive values of serum T4 and TSH concentrations obtained 19 days after treatment in order to predict the development of iatrogenic hypothyroidism 6-9 months after 131I treatment. METHODS: Serum T4, TSH and creatinine concentrations were measured 19 days and 6-9 months after 131I treatment. The prevalence of iatrogenic hypothyroidism was assessed with the results obtained 6-9 months after 131I treatment. RESULTS: The prevalence of overt and subclinical hypothyroidism 6-9 months after 131I treatment was 40.0% (22/55 cats) and 12.7% (7/55 cats). Overt hypothyroidism with azotaemia was diagnosed in 8/55 (14.5%) cats. The positive and negative predictive values for the prediction of the development of iatrogenic hypothyroidism 6-9 months after 131I treatment were 72.2% and 80.0%, respectively, for a low serum T4 concentration, and 75.0% and 44.6%, respectively, for an increased serum TSH concentration. CONCLUSIONS AND RELEVANCE: The use of an individualised scoring system is effective in determining the 131I dose for the treatment of hyperthyroid cats. However, the prevalence of overt hypothyroidism was higher in comparison with other studies using different dosing protocols. Further studies comparing the efficacy of individualised scoring systems and different fixed doses to determine which method is superior are warranted.

Assessment and prediction of acute kidney injury in patients with decompensated cirrhosis with serum cystatin C and urine N-acetyl-ß-D-glucosaminidase.

BACKGROUND AND AIM: For appropriate management of acute kidney injury (AKI) in cirrhotic patients, accurate differentiation of the types of AKI, prerenal azotemia (PRA), hepatorenal syndrome (HRS), and acute tubular necrosis (ATN) is very important. Urine N-acetyl-ß-D-glucosaminidase (NAG) has been proposed as a good tubular injury marker in many studies, but its efficacy in cirrhosis is unclear. This study was performed to evaluate the usefulness of urine NAG in patients with decompensated cirrhosis. METHODS: In 114 hospitalized patients with decompensated cirrhosis, we assessed serum creatinine, cystatin C, and urine NAG levels as markers for AKI differentiation and development and patient mortality. RESULTS: Thirty patients diagnosed with AKI at baseline had significantly higher serum creatinine and cystatin C levels, urine NAG levels, and Child-Pugh scores than those without AKI. Only urine NAG levels were significantly higher in patients with ATN than those with PRA or HRS (116.1 ± 46.8 U/g vs 39.4 ± 20.2 or 54.0 ± 19.2 U/g urinary creatinine, all P < 0.05). During a median follow up of 6.1 months, AKI developed in 17 of 84 patients: PRA in nine, HRS in six, and ATN in three. Higher serum cystatin C and urine NAG levels were independent predictors of AKI development in patients with decompensated cirrhosis. Survival was significantly associated with low serum cystatin C and urine NAG levels. CONCLUSION: Serum cystatin C and urine NAG levels are useful to differentiate types of AKI and are strong predictors for AKI development and mortality in patients with decompensated cirrhosis.

Renal azotemia and associated clinical and laboratory findings in dogs with Babesia rossi infection.

The occurrence of acute kidney injury in canine babesiosis is not well documented. Furthermore, interpretation of urine specific gravity (USG) to assess renal concentrating ability is hampered by the frequent presence of hemoglobinuria in this disease. This cross-sectional study aimed to test the hypothesis that renal azotemia (RA) is underdiagnosed according to current canine babesiosis literature by determining its occurrence at presentation, using urine osmolality instead of USG to measure urinary concentration. The second objective was to examine potential associations between the presence of RA and selected clinical and laboratory variables at presentation. Medical records available from 3 previously performed prospective data collections were reviewed retrospectively. Client-owned dogs that were diagnosed with babesiosis caused by Babesia rossi, were included if a complete blood count, biochemistry profile, and urinalysis was performed at admission. Urine osmolality was measured to identify dogs with RA. Differences between dogs with RA and dogs without RA were assessed by nonparametric statistics. One hundred and fifty-two dogs were included, of which 26 (17%) were azotemic at admission. The occurrence of RA was 14% (21/152), hence 81% (21/26) of all azotemic dogs were diagnosed with RA. In contrast, when diagnosis of RA was based on an admission USG < 1.030, only 23% (6/26) of the azotemic dogs would have been considered to have RA. Several signalment and clinicopathological findings were found to be associated with the presence of RA, including older age, and the presence of collapse, hypoglycemia, hyperphosphatemia, cerebral babesiosis, and acute respiratory distress syndrome. Lastly, survival at discharge was significantly lower in dogs diagnosed with RA at presentation. Our results clarified that RA is more common than previously reported in B. rossi. This study also demonstrated that USG determination is not a reliable method to evaluate renal concentrating ability in azotemic dogs with babesiosis. Thus, if available, urine osmolality should be part of the diagnostic work-up of dogs infected with B. rossi to avoid misclassification of dogs with RA as having prerenal azotemia. If urine osmolality cannot be measured, clinicians should realize that most azotemic dogs with B. rossi infection have RA.

GRHL2 Is Required for Collecting Duct Epithelial Barrier Function and Renal Osmoregulation.

Collecting ducts make up the distal-most tubular segments of the kidney, extending from the cortex, where they connect to the nephron proper, into the medulla, where they release urine into the renal pelvis. During water deprivation, body water preservation is ensured by the selective transepithelial reabsorption of water into the hypertonic medullary interstitium mediated by collecting ducts. The collecting duct epithelium forms tight junctions composed of barrier-enforcing claudins and exhibits a higher transepithelial resistance than other segments of the renal tubule exhibit. However, the functional relevance of this strong collecting duct epithelial barrier is unresolved. Here, we report that collecting duct-specific deletion of an epithelial transcription factor, grainyhead-like 2 (GRHL2), in mice led to reduced expression of tight junction-associated barrier components, reduced collecting duct transepithelial resistance, and defective renal medullary accumulation of sodium and other osmolytes. In vitro, Grhl2-deficient collecting duct cells displayed increased paracellular flux of sodium, chloride, and urea. Consistent with these effects, Grhl2-deficient mice had diabetes insipidus, produced dilute urine, and failed to adequately concentrate their urine after water restriction, resulting in susceptibility to prerenal azotemia. These data indicate a direct functional link between collecting duct epithelial barrier characteristics, which appear to prevent leakage of interstitial osmolytes into urine, and body water homeostasis.

Bone lymphoma with multiple negative bone biopsies.

This article describes a 71-year-old man with right knee pain, prerenal azotemia, hypercalcemia, and a mass in the distal femur. Although testing, including bone marrow biopsy, initially ruled out myeloma, an open surgical biopsy eventually confirmed the diagnosis as lymphoma involving the bone with classic histologic findings of mature B-cell neoplasm of germinal cell origin.

Fatal proteinuric kidney disease in a 30-month-old German Fleckvieh heifer caused by unilateral focal segmental glomerulosclerosis subsequent to a non-functional counterpart kidney.

INTRODUCTION: A case of secondary focal segmental glomerulosclerosis (FSGS) in a heifer is presented. A 30-month-old female German Fleckvieh heifer showed deterioration of the general condition, a poor nutritional status, proteinuria, hypoalbuminemia, and renal azotemia. Pathologically, it was diagnosed with unilateral hydronephrosis, and contralateral renal fibrosis with numerous cysts. Histologically, the fibrotic kidney showed FSGS, hyaline reabsorption droplets in proximal tubular epithelial cells, interstitial fibrosis, and tubulointerstitial inflammation. Apart from that, thrombotic microangiopathy (TMA) was seen in few renal arteries and meningeal arterioles. Pathogenesis of FSGS secondary to unilateral renal parenchymal loss (hydronephrosis) and TMA is discussed.