Urine Protein-to-creatinine Research Articles

Association of Health Literacy and Numeracy With Lupus Knowledge and the Creation of the Lupus Knowledge Assessment Test.

Limited health literacy and numeracy are associated with worse patient-reported outcomes and higher disease activity in systemic lupus erythematosus (SLE), but which factors may mediate this association is unknown. We sought to determine the association of health literacy and numeracy with SLE knowledge. Patients with SLE were recruited from an academic center clinic. Participants completed validated assessments of health literacy (Newest Vital Sign [NVS]; n = 96) and numeracy (Numeracy Understanding in Medicine Instrument, Short Version [S-NUMI]; n = 85). They also completed the Lupus Knowledge Assessment Test (LKAT), which consists of 4 questions assessing SLE knowledge that were determined through consensus expert opinion for their wide applicability and importance related to self-management of the disease. Descriptive statistics and multivariable logistic regression modeling were used to analyze the results. In our SLE cohort (n = 125), 33% (32/96) had limited health literacy and 76% (65/85) had limited numeracy. The majority correctly identified that hydroxychloroquine prevented SLE flares (91%); however, only 23% of participants correctly answered a numeracy question assessing which urine protein to creatinine (UPC) ratio was > 1000 mg/g. The mean LKAT score was 2.7 out of 4.0. Limited health literacy, but not numeracy, was associated with lower knowledge about SLE as measured by the LKAT, even after adjusting for education. Patients with SLE with limited health literacy had lower knowledge about SLE. The LKAT could be further refined and/or used as a screening tool to identify patients with knowledge gaps. Further work is needed to improve patients' understanding of proteinuria and investigate whether literacy-sensitive education can improve care.

Alterations of selected serum biochemical and urinary parameters in dogs with chronic enteropathy.

Background:No specific study on concurrent nephropathy has been conducted in dogs with chronic enteropathy (CE), except for soft-coated Wheaten Terriers. Moreover, limited information exists regarding the urinary profile in dogs with CE.Aim:To describe, compare, and discuss the alterations in selected serum biochemical and urinary parameters in dogs with CE.Methods:Multicentric retrospective study on dogs with CE diagnosed after exclusion of extra-gastrointestinal diseases. In addition, dogs with azotemia and lower urinary tract diseases were excluded. Information on canine chronic enteropathy clinical activity index (CCECAI) score, muscular condition score (MCS), presence of glycosuria, proteinuria [urine protein-to-creatinine (UPC) ratio > 0.5], and/or cylindruria (>1–2 casts/hpf) at diagnosis were gleaned from the medical records. Dogs were retrospectively classified as food-responsive enteropathy, immunosuppressant-responsive enteropathy, or nonresponsive enteropathy based on the presence of gastrointestinal histological inflammation and the treatment response. In addition, based on the serum albumin concentration (ALB), dogs were classified as having protein-losing enteropathy (PLE).Results:Ninety CE dogs were included. Fifty-two dogs had mild-to-severely decreased MCS and 38 dogs showed altered urinary parameters. No significant associations were found between CCECAI and altered urinary parameters. No significant association was found between PLE dogs and altered urinary parameters. PLE dogs showed higher prevalence of proteinuria than non-PLE dogs (p = 0.03; OR = 2.8; 95% CI = 1–6.8). Conclusion:Despite the presence of altered urinary profile in dogs with CE, further studies are needed to explore a possible link between gastrointestinal and renal inflammation.

Baseline renal function and adverse outcomes in pregnancies complicated by pregestational diabetes

Objective To examine the relationship between baseline renal function (serum creatinine, urine protein to creatinine ratio) in women with diabetes and adverse pregnancy outcomes. Study Design This was a retrospective cohort study of singleton pregnancies with pregestational diabetes and baseline renal function tests <20 weeks gestational age (wga) from the years 2007 to 2013. Those with baseline creatinine ≥1.2 mg/dL were excluded due to the association of renal disease with adverse outcomes. The primary outcome was the development of preeclampsia with severe features at <34 wga. Secondary outcomes were preeclampsia at any gestational age, preterm birth, indicated preterm birth, small for gestational age, and a neonatal adverse outcomes composite. The relationship between baseline renal function and the primary outcome was assessed with ROC curves. Objective cutoffs were determined by the Liu method. Outcomes were compared using univariable and multivariable analyses. Results Baseline renal function was assessed in 321 women with pregestational diabetes. With baseline serum creatinine <1.2 mg/dL serum creatinine was not associated with preeclampsia <34 weeks (AUC 0.47, 95% CI = 0.32–0.63). Urine protein to creatinine (UPC) ratio was moderately associated with preeclampsia <34 weeks with area under curve (AUC) 0.56 (0.39–0.74). Baseline creatinine above the Liu cutoff (0.65 mg/dL) was not significantly associated with primary or secondary outcomes (Table 1). UPC above the Liu cutoff (0.21) was significantly associated with severe preeclampsia <34 wga (24% vs 3.7%, aOR = 6.6, 95% CI = 2.1–20.8), with development of preeclampsia at any gestational age (56% vs 23.4%, aOR = 3.3, 95% CI = 1.4–7.9), and preterm birth (80% vs 36.2%, aOR 6.5 95% CI = 2.3–18.1). Conclusion Creatinine was not associated with adverse pregnancy outcomes at thresholds <1.2 mg/dL in women with pregestational diabetes. Those with a baseline UPC ≥ 0.21 have an increased risk of preeclampsia and preterm delivery. Baseline 24 hr urine protein should be obtained in these patients to aid in counseling and future diagnosis of preeclampsia. Key Points Baseline renal function tests are recommended in patients with pregestational diabetes, but values associated with pregnancy risk are poorly defined. This study evaluated the relationship between baseline renal function tests in patients with pregestational diabetes and adverse pregnancy outcomes. We found urine protein to creatinine ratio ≥0.21 to be associated with the development of severe preeclampsia <34 weeks gestational age as well as preeclampsia at any gestational age.

Influence of preanalytical factors on feline proteinuria.

To date, little information is available about the effect of preanalytical factors on the urinary protein-to-creatinine (UPC) ratio in cats. We aimed to evaluate the effect of a commercially available cat litter, creatinine measurements at three different dilutions of urine, and different storage conditions on the UPC ratio in cats. Feline urine specimens were prospectively collected. Twenty-two whole-urine specimens were placed uncovered and in contact with cat litter for 1hour; 25 urine supernatants were diluted 1:10, 1:20, and 1:100 for creatinine measurements. The correlation, difference, agreement, and concordance in classifying specimens according to International Renal Interest Society staging were determined. Storage effects on UPC ratios were assessed in specimens stored for 6hours at +20℃ (n=20), 1week at +4℃ (n=20), and 3months at -20℃ (n=25). Specimens were also subjected to four freeze-thaw cycles (n=20). Results were compared, and clinical significance was assessed by comparing each UPC ratio to the inter-assay range of the baseline value. Exposure to cat litter did not affect UPC ratios. A positive proportional bias was found in the 1:100 dilution compared with the 1:20 dilution; however, concordance was high for all comparisons. At +20, +4℃, and after four repeated freeze-thaw cycles, UPC ratios were stable. Compared with baseline values, UPC ratios decreased (P<.01) after 8 and 12weeks at -20℃. However, all UPC ratios were within the inter-assay variability of the baseline value. Exposure to cat litter did not affect UPC ratios, but further studies are necessary to evaluate other potential variables. The effects of the dilutions and storage conditions were clinically acceptable, although the 1:20 and 1:100 dilutions were not perfectly comparable.

Comparison of urinary protein-to-creatinine ration, serum albumin, serum creatinine and systolic arterial blood pressure of glomerular injury cases in dogs with chronic kidney disease

This study aims at assessing the prevalence of glomerular alterations in dogs with chronic kidney disease (CKD) and comparing the clinical and laboratory parameters. The tests conducted include a double-blind histopathological assay conducted by two pathologists, urine tests including inactive sediment, urinary protein-to-creatinine (UPC), serum albumin and serum creatinine, as well as measurement of the systolic arterial blood pressure. The prevalence of glomerular injuries was determined and the predominant injury was compared with a group comprised of the remaining injuries. The study included 24 dogs with CKD. The results revealed a predominance of membranous glomerular alterations 17/24 (70,83%), followed by glomerulosclerosis 3/24 (12,50%), membranoproliferative injuries 2/24, glomerulocystic atrophy 1/24 and glomerular amyloidosis 1/24. Amyloidosis presented the highest UPC while the membranoproliferative injury presented the lowest mean concentration of serum albumin. Higher values in the UPC did not correspond with lower mean serum albumin values. Glomerulosclerosis presented the highest mean systolic blood pressure and glomerular atrophy presented the highest creatinine values. When comparing membranous injuries with a group comprised of the remaining injuries, the UPC did not present significant differences between the groups. Renal amyloidosis was included in the group with the lowest systolic arterial blood pressure values while membranoproliferative injury was included in the group with highest UPC. The group called “others” presented the highest creatinine value. Dogs with CKD may present several types of glomerular injuries with similar clinical and laboratory profiles. This study observed a predominance of membranous glomerular injuries, followed by membranoproliferative injuries, glomerulocystic atrophy and amyloidosis.

Is proteinuria a rare condition in apparently healthy and sick cats? A feline practice experience (2007-2018).

Background:Proteinuria is assumed to be less frequent in cats than in dogs and is mainly associated with chronic kidney disease (CKD). Aim:The current study aimed to evaluate and compare urine protein-to-creatinine (UPC) values retrospectively in cats visited for comprehensive annual health check or for presenting systemic clinical signs related to CKD.Methods:UPC ratio was retrospectively evaluated in 112 owned cats, out of which 51 (45.5%) were apparently healthy cats according to their owners who visited for comprehensive annual health checks and 61 (54.5%) sick cats, presenting systemic clinical signs suggesting CKD, such as weight loss or polyuria/polydipsia, among others.Results:Based on UPC, the present study found that 54.5% of all cats included were borderline proteinuric or proteinuric, having increased UPC (UPC ≥ 0.2), with 35.7% included in the sick group and 18.7% in the health-check group. Increased UPC was also statistically associated with azotemia and isosthenuria (urinary-specific gravity between 1,008 and 1,035) in both sick and health-check groups of cats.Conclusion:Independent of the reason for their medical visit, it could be concluded that borderline proteinuria and proteinuria were statistically mainly related to CKD in cats. Furthermore, the measurement of UPC could be very useful in the detection and management of CKD in apparently healthy cats during a medical visit for annual health check irrespective of the age.

Anti-Inflammatory, Antioxidant, and Antifibrotic Effects of Kefir Peptides on Salt-Induced Renal Vascular Damage and Dysfunction in Aged Stroke-Prone Spontaneously Hypertensive Rats.

The increased prevalence of renal dysfunction and chronic kidney disease (CKD) and the high costs and poor outcomes of treatment are a significant health issue. The consequence of chronic high blood pressure is the increased prevalence of target organ end-stage renal disease, which has been proven to be a strong independent risk factor for adverse cardiovascular disease. A previous study showed that kefir products have anti-inflammatory and anti-hypertensive activities and immunological modulation functions. However, no data regarding the beneficial effects of kefir peptides (KPs) on salt-induced renal damage or related kidney diseases are available. In this study, KPs were orally administered to aged salt-induced stroke-prone spontaneously hypertensive (SHRSP) rats, and the effects of KPs against inflammation and oxidative stress and their ability to protect against renal dysfunction were evaluated. Fifty-five-week-old SHRSP rats under induction with 1% NaCl in drinking water for 4 weeks showed multiple renal injuries with increased renal inflammation, fibrosis, oxidative stress, tubular atrophy, and glomerulosclerosis. In contrast, oral gavage with KPs reduced the urine protein to creatinine (UPC) ratio, the fractional excretion of electrolytes (FeNa and FeCl), extracellular matrix deposition, and the interstitial fibrotic α-smooth muscle actin (α-SMA) levels in salt-induced SHRSP rats. The renal infiltration of inflammatory cells; the release of monocyte chemoattractant protein-1 (MCP-1), vascular cell adhesion molecule-1 (VCAM-1), endothelin-1 (ET-1), and the cytokine nucleotide-binding oligomerization domain (NOD)-like receptor family pyrin domain containing 3 (NLRP3) and transforming growth factor-β (TGF-β); the reactive oxygen species (ROS) levels; and histopathological lesions were also decreased in salt-induced SHRSP rats. Furthermore, KP treatment significantly increased the renal superoxide dismutase (SOD) activity and the glomerular filtration rate (GFR), which exerted potent protection against salt-induced chronic kidney disease in SHRSP rats. The results of this study suggest that KPs ameliorate salt-induced renal damage, tubular atrophy, and glomerular dysfunction through anti-inflammatory, antioxidative stress, and antifibrotic activities, and might be a promising protective agent against high salt-induced renovascular-related diseases.

P0294WHEN DO WE HAVE TO SUSPECT THAT A PREECLAMPSIA MASKS A GLOMERULOPATHY?

Abstract Background and Aims Between the 2-8% of pregnancies suffer preeclampsia (PE). In the literature, there have been reported cases of glomerulopathy debuted by pregnancy (GDP) which are initially missdiagnosed as PE. These cases are unusual and not well-defined. We aimed to evaluate clinical and analytical factors that allow us to suspect that a PE masks a GDP. Method Retrospective study that included pregnant patients with a postpartum histological diagnosis of glomerulopathy who had been missdiagnosed as PE during pregnancy. We compared them with patients who suffered PE with full recovery after childbirth. We evaluate demographic variables of pregnant women and newborns, clinical variables related to pregnancy and childbirth, blood pressure (BP) and analytical variables before pregnancy and postpartum (serum creatinine (sCrea), estimated glomerular filtration rate by CKD-EPI equation (eGFR), serum uric acid (sUA), ratio of urine protein to creatinine (UPCR)). Results Thirty patients were included in the study ,10 patients with a postpartum histological diagnosis of glomerulopathy who had been diagnosed as PE during the pregnancy and 20 patients with a diagnosis of PE without GDP, baseline characteristics are described in attached table. Glomerulopathy was diagnosis through renal biopsy, main indication of renal biopsy was the persistence of proteinuria and/or sediment abnormalities after 4 months of childbirth. The diagnoses were: IgA nephropathy (3, 33.3%), focal and segmental hyalinosis (2, 22.2%), X-linked Alport syndrome (2, 22.2%), diabetic nephropathy (1, 11.1%), lupus nephritis (1, 11.1%) and chronic interstitial nephropathy (1, 11.1%). Pregnant women with GDP showed higher prevalence of smoking habit and major value of sCrea and sUA (figure). Regarding to pregnancy factors, patients with GDP had significant higher prevalence of primiparous gestation (100% vs 40%, p=0.002), twin gestation (20% vs 0%, p=0.03), premature newborn (50% vs 15%, p=0.01) and higher weight gain during pregnancy (13.9±5.8 vs 9.5±3.6 kg, p=0.01). Furthermore, in the postpartum data we objected a higher value of systolic/diastolic BP (145.6±10.3 / 89.4±12.1 vs 128.5±10.0 / 80.0±6.3 mmHg, p&amp;lt;0.05), sCrea (0.83±0.3 vs 0.54±0.2 mg/dl, p=0.02), sUA (5.8±1.3 vs 3.4±0.8 mg/dl, p&amp;lt;0.001) and UPCR (3046 [613-4179] vs 802 [281-948] mg/g, p=0.05) in patient with NPD. Conclusion Our results suggest that clinical and analytical variables in pregnancy and post-partum allow clinicians suspect a glomerulopathy in the setting of PE. Patients diagnosed as PE who develop GDP had higher prevalence of smoking habit, primiparous gestation, twin gestation and premature newborns. In addition, they also have higher weight gain during pregnancy, worse renal function and major sUA before pregnancy and after childbirth, and major UPCR and BP after childbirth; compared with patients with PE and full recovery after childbirth.

Study Design of the Phase 3 Sparsentan Versus Irbesartan (DUPLEX) Study in Patients With Focal Segmental Glomerulosclerosis

IntroductionFocal segmental glomerulosclerosis (FSGS), a histologic lesion in the kidney caused by varied pathophysiological processes, leads to end-stage kidney disease in a large proportion of patients. Sparsentan is a first-in-class orally active compound combining endothelin type A (ETA) receptor blockade with angiotensin II type 1 (AT1) receptor antagonism in a single molecule. A Randomized, Multicenter, Double-Blind, Parallel, Active-Control Study of the Effects of Sparsentan, a Dual Endothelin Receptor and Angiotensin Receptor Blocker, on Renal Outcomes in Patients With Primary FSGS (DUPLEX) study evaluates the long-term antiproteinuric efficacy, nephroprotective potential, and safety profile of sparsentan compared with an AT1 receptor blocker alone in patients with FSGS.MethodsDUPLEX is a multicenter, international, phase 3, randomized, double-blind, active-controlled study of sparsentan in patients with FSGS. Approximately 300 patients aged 8 to 75 years, inclusive (United States), and 18 to 75 years, inclusive (outside United States) will be randomized 1:1 to daily treatment with sparsentan or irbesartan. After renin-angiotensin-aldosterone system inhibitor washout, treatment will be administered for 108 weeks, with the final assessment at week 112, four weeks after withdrawal of study drug.ResultsThe primary endpoint will be the slope of estimated glomerular filtration rate from week 6 to week 108. A novel surrogate efficacy endpoint, the proportion of patients achieving urinary protein-to-creatinine (UP/C) ratio of ≤1.5 g/g and >40% reduction from baseline in UP/C (FSGS partial remission endpoint: FPRE), will be evaluated at a planned interim analysis at week 36. Safety and tolerability of sparsentan will also be assessed.ConclusionThe phase 3 DUPLEX study will characterize the long-term antiproteinuric efficacy and nephroprotective potential of dual ETA and AT1 receptor blockade with sparsentan in patients with FSGS.

Immune-complex glomerulonephritis in cats: a retrospective study based on clinico-pathological data, histopathology and ultrastructural features

BackgroundChronic kidney disease (CKD) has typically a non-immune mediated origin in cats and immune-complex glomerulonephritis (ICGN) is scarcely described. Aims of this study were to characterize ICGN by light and electron microscopy and identify associations with clinico-pathological findings. In addition, comparisons between cats with ICGN and non immune-complex glomerulonephritis (non-ICGN) were performed.Renal samples examined between 2010 and 2019 were considered if both light and electron microscopy were performed. Signalment, feline immunodeficiency virus (FIV) and leukemia virus (FeLV) status, serum creatinine concentration, urine protein-to-creatinine (UPC) ratio, systolic blood pressure (SBP) and International Renal Interest Society (IRIS) stage were retrieved and used for comparisons.ResultsSixty-eight client-owned cats were included. Thirty-seven cats (54.4%) had ICGN and 31 (45.6%) non-ICGN. Eighteen (48.6%) with ICGN had membranous glomerulonephropathy (MGN), 14 (37.8%) membranoproliferative glomerulonephritis (MPGN), and 5 (13.5%) mesangioproliferative glomerulonephritis (MeGN). Clinico-pathological data were not associated with any type of ICGN. Among cats with non-ICGN, 11 (35.5%) had end-stage CKD, 9 (29%) focal segmental glomerulosclerosis, 6 (19.4%) global and multifocal mesangiosclerosis, 2 (6.5%) glomerular atrophy, 2 (6.5%) renal dysplasia and 1 (3.1%) amyloidosis. Eight (25.8%) cats with non-ICGN had chronic interstitial nephritis (CIN) grade 1, 13 (41.9%) grade 2 and 10 (32.3%) grade 3; creatinine and UPC ratio increased with CIN grades (p = 0.001, p < 0.001). Cats with ICGN were more frequently FIV or FeLV-infected (OR:11.4; 95%CI:1.4–94.4; p = 0.024), had higher UPC ratio (OR:6.8; 95%CI:2.5–18.2; p < 0.001) and were younger (OR:0.9; 95%CI:0.7–1.0; p = 0.042) than cats with non-ICGN.ConclusionsMGN and MPGN were the most common morphological diagnoses of ICGN in cats. Unfortunately, none of the investigated findings differentiated ICGN morphological diagnoses. Serum creatinine concentration and UPC ratio were directly associated with grades of CIN (p = 0.001 and p < 0.001, respectively), confirming previous literature. More ICGN than non-ICGN was observed in cats with retroviral infections, younger cats and higher UPC ratio.

Simplified Algorithm for Evaluation of Proteinuria in Clinical Practice: How should A Clinician Approach?

Background:Proteinuria is a common laboratory finding among children and adolescents. It can be identified as either a transient or a persistent finding and can represent a benign condition or a serious disease.Methods:Pertinent medical literature for asymptomatic proteinuria in children and adolescents published in English was searched between January 1980 and May 2017 using PubMed, MEDLINE, EMBASE, and Google Scholar research databases. Of the 64 reviewed articles, 24 studies were eligible for inclusion.Results:Random spot urine protein-to-creatinine (PCR) ratio is widely used to reliably detect proteinuria. The normal value for the spot PCR in children aged 2 years or older is less than 0.3. In children aged below 2 years, the PCR can be as high as 0.5. Orthostatic proteinuria is defined as urine PCR greater than 0.3 detected in a urine specimen during the daytime activity but less than 0.3 on the first morning void specimen. PCR above 3.0 signifies heavy proteinuria as seen in nephrotic syndrome. Orthostatic proteinuria is a frequent cause of proteinuria in asymptomatic children and adolescents, which require no specific therapy except for health maintenance follow-up. Pediatric nephrologist referral is indicated when the proteinuria is constant and persists over 6 months or is associated with hematuria, hypertension, or renal dysfunction.Conclusions:We provide a simplified diagnostic algorithm for evaluation of proteinuria in primary care adolescents who appear well and in whom proteinuria is incidentally discovered during a routine examination.

Evaluation of effect over time after oral administration of telmisartan for chronic kidney disease in cats

Angiotensin receptor blockers, such as telmisartan, are considered effective in the treatment of hypertension and proteinuria due to chronic kidney disease (CKD) in cats. It selectively blocks the AT1 receptor and does not affect the AT2 receptor, thus effectively blocking the activity of the renin angiotensin aldosterone system. This study aims to compare over time the changes in various indicators, including systemic hypertension and proteinuria, before and after the administration of telmisartan in cats with CKD. Decrease in blood pressure (BP) (p&lt;0.001) and urine protein to creatinine (UP/C) ratio (p&lt;0.001) were found to be statistically significant over time after the administration of telmisartan. BP and the UP/C ratio were 160 ± 22.2 and 0.50 ± 0.647 before telmisartan administration (Day 0), 150 ± 21.0 and 0.27 ± 0.487 on the 30th day (Day 30), 150 ± 17.0 and 0.25 ± 0.376 on the 60th day (Day 60), and 140 ± 17.8 and 0.15 ± 0.233 on the 90th day (Day 90) after administration, respectively. BP and UP/C were statistically significantly lower in cats with CKD over time at each time point from Day 0 to Day 90 at 30 day intervals. Especially after 90 days of telmisartan administration, the improvement of BP and UP/C were estimated to be about 20 mmHg and 0.35, respectively. In conclusion, the oral administration of telmisartan to cats with CKD is effective in improving BP and proteinuria, which has a positive effect on long-term survival in cats with CKD.

Evaluation of the analytical variability of urine protein-to-creatinine ratio in cats.

Proteinuria quantification with the urinary protein-to-creatinine (UPC) ratio is part of the diagnostic process in feline patients suspected of chronic kidney disease (CKD). In affected cats, monitoring and substaging of the UPC according to the International Renal Interest Society (IRIS) guidelines is also necessary for appropriate patient management. No information is available about the possible effects of analytical variability on urinary proteins (UPs) and the UPC ratio in cats. This study aimed to determine whether imprecision and method-dependent differences due to the two dye-binding methods, pyrogallol red-molybdate (PRM) and Coomassie brilliant blue (CBB), could affect IRIS substaging. Urine samples were collected from proteinuric and nonproteinuric cats. Intra-assay and inter-assay repeatability were assessed with both the PRM and CBB methods. Urinary supernatants (n=120) were tested using both methods. Agreement between the methods and concordance with sample classification according to IRIS guidelines were determined. On average, the PRM method yielded a higher CV (UP 8.4±5.2%; UPC 9.5±4.8%) than the CBB method (UP 5.6±2.6%; UPC 7.2±2.6%), but similar rates of misclassification were found in samples with UPC ratios close to the IRIS cut-off. Although the two methods were correlated, the CBB method tended to yield UPs and UPC ratios that were significantly higher (P<0.0001) than that of the PRM method. The Passing-Bablok test also found constant and proportional errors between the PRM and CBB methods. Concordance in substaging samples according to IRIS was good (k coefficient=0.62). The two methods were precise, but the higher UPC ratios obtained with the CBB methods might affect the interpretation using the IRIS guidelines and clinical decisions.

Use of urinary γ-glutamyl transferase (GGT) to monitor the pattern of proteinuria in dogs with leishmaniasis treated with N-methylglucamine antimoniate

The aim of this study was to assess if the coupled analysis of the urinary protein to creatinine (UPC) ratio and of the GGT/UC ratio (the ratio between urinary γ-glutamyl transferase activity and urinary creatinine) may be used in treated leishmaniotic dogs to differentiate dogs with transient impairment of tubular function from dogs with persistent tubular damage.To this aim, 40 urine from 10 proteinuric and leishmaniotic dogs that at the first visit had high GGT/UC ratio, consistent with tubular damage, were collected and analyzed before treatments and 2, 4 and 6 weeks after treatment with N-methylglucamine antimoniate and allopurinol.Compared with pre-treatment values, at the end of the study period the UPC ratio decreased only in 5/10 dogs, which, however, were still proteinuric or borderline proteinuric. Conversely, the GGT/CU ratio decreased in 8/10 dogs and in 3 of them the values at the end of the study period were below the threshold consistent with tubular proteinuria. The GGT/UC values at 6 weeks was significantly lower than before treatment. However, transient increases were frequent for both the analytes.These results indicate that in most of the dogs that remain proteinuric after treatment, likely due to the persistent glomerular damage, the GGT/UC ratio tends to normalize. This suggests that in these dogs tubular proteinuria at admission depends on functional impairment of tubular cells likely due to the overflow of proteins from damaged glomeruli. However, tubular proteinuria occasionally persists, suggesting that tubulointerstitial damages persist even in dogs responsive to treatments.

Short-term effects of dietary supplementation with amino acids in dogs with proteinuric chronic kidney disease.

This retrospective study investigated the impact of amino acid supplementation on body weight, serum albumin, creatinine and urea concentrations, and urine protein-to-creatinine (UPC) ratio in proteinuric dogs with chronic kidney disease (CKD). Forty-six client-owned azotemic dogs with spontaneous proteinuric CKD already on a renal diet and in therapy with enalapril were included. After approximately 1 month of treatment (baseline), 29 dogs received oral amino acid supplementation daily (group A) and 17 dogs did not (group B). The parameters under investigation were determined at baseline and after 4 to 8 weeks in both groups. Compared to baseline, body weight and serum albumin increased (P < 0.01, P < 0.05, respectively) at follow-up in group A, but did not change in group B. Serum creatinine concentration did not change in both groups; urea concentration (P < 0.05) and UPC ratio (P < 0.01) decreased in group B, but not in group A. Supplementation with amino acids increased body weight and serum albumin concentration in these dogs but it might have prevented a decrease in proteinuria and urea concentration.

Spot urine protein measurements in normotensive pregnancies, pregnancies with isolated proteinuria and preeclampsia

We performed a prospective, longitudinal study of pregnant women presenting to their first obstetrics visits to characterize the changes in spot urine protein-to-creatinine (UPCR) and albumin-to-creatinine ratios (UACR) in normotensive pregnancies, as well as identify clinical characteristics associated with isolated proteinuria and preeclampsia. We measured spot urinary albumin, protein, and creatinine at the first prenatal visit, end of the second trimester, and at delivery. In the normotensive pregnancies (n = 142), we found that from the beginning of pregnancy to delivery, UACR increased by a median [interquartile range (IQR)] of 14.7 mg/g Cr (3.74-51.8) and UPCR by 60 mg/g Cr (30-130) (P < 0.001 for both changes). Isolated proteinuria (defined as UPCR > 300 mg/g Cr in the absence of hypertension) was identified in 19/142 (13.4%) normotensive pregnancies. Increases in systolic and diastolic blood pressure from early pregnancy to delivery and increases in UACR from early to midpregnancy were associated with isolated proteinuria at delivery. Twelve women developed preeclampsia. Nulliparity, early, and midpregnancy diastolic blood pressures were strongly associated with the development of preeclampsia, but early changes in UACR were not. In conclusion, women who develop isolated proteinuria at delivery have a larger increase in blood pressure than women without proteinuria and have a "microalbuminuric" phase earlier in gestation, unlike women who develop preeclampsia. These findings suggest a different mechanism of urine protein excretion in women with isolated proteinuria as compared with women with preeclampsia, where proteinuria has a more abrupt onset.

Measurement of proteinuria in dogs: analytic and diagnostic differences using 2 laboratory methods.

Urinary protein-to-creatinine (UPC) ratio is an early diagnostic and prognostic marker of renal disease in dogs. Pyrogallol red molybdate (PRM) and Coomassie brilliant blue (CBB) are the most popular dye-binding assays for measurement of proteinuria. Published guidelines recommend strict cut-off points to substage patients with chronic renal diseases, irrespective of the assay applied. However, analytic variability and method-dependent differences could affect substaging of patients. The aims of this study were to analytically validate the CBB assay to evaluate possible method-dependent differences with PRM in urinary protein (UP) determination, and to assess the influence of such differences in substaging according to the International Renal Interest Society (IRIS). Urine was collected from healthy and proteinuric dogs. Intra-assay and inter-assay repeatability (imprecision), linearity under dilution (LUD), and spiking recovery (inaccuracy) were determined for the CBB assay. Split samples were measured with PRM and CBB, and agreement between methods and concordance in classification according to IRIS guidelines was determined. The CBB assay was precise (< 10%) at all urine protein concentrations after excluding outliers from the intra-assay precision assay of high urine protein concentrations. Acceptable accuracy was demonstrated with both LUD and spiking recovery test. Both UP and UPC determined by CBB were significantly higher (P < .0001) than those obtained with PRM, and both a constant and proportional bias were present. Concordance of IRIS substaging was only moderate. The CBB is precise and accurate, but the higher UPC obtained with CBB vs PRM may affect interpretation of the IRIS guidelines.

Long-term follow-up of renal function assessing serum cystatin C in dogs with diabetes mellitus or hyperadrenocorticism.

Serum cystatin C (sCysC) is used as biomarker for glomerular filtration rate (GFR). The effects of diabetes mellitus (DM) on renal function in dogs are unclear. Some renal variables have been evaluated in dogs with hyperadrenocorticism (HAC), but not sCysC. The purpose of this study was the validation of a particle-enhanced nephelometric immunoassay (PENIA) for measuring canine sCysC, and to assess renal function in dogs with DM or HAC. A PENIA was analytically validated for canine sCysC by determining imprecision and linearity. In a longitudinal 6-month study, renal function of 14 DM dogs was assessed, using serum creatinine, GFR, urinary protein-to-creatinine (UPC) ratio, urinary markers, systolic blood pressure (SBP), and sCysC, and compared to 17 healthy dogs at baseline. Furthermore, sCysC was measured at initial presentation and during a 12-month follow-up in 22 HAC dogs. The sCysC intra- and inter-assay variation coefficients were < 8% and highly linear (r = .997). About 33% and 67% of DM dogs had persistent proteinuria and systemic hypertension, respectively, but there were no significant differences in GFR, UPC, and urinary markers over time, and compared with healthy dogs at initial presentation. Serum CysC decreased significantly (P < .05) over time within the DM group. It did not change significantly over time within the HAC group. A PENIA measured sCysC linearly and precisely. There were no clinically relevant renal alterations over time in dogs with DM, although persistent proteinuria was observed. In dogs with HAC, sCysC measurement was not useful, although significant GFR changes occurred over time.

The effect of renal diet in association with enalapril or benazepril on proteinuria in dogs with proteinuric chronic kidney disease

Treating proteinuria in dogs reduces the progression of chronic kidney disease (CKD); renal diets and angiotensin-converting enzyme (ACE)-inhibitors are cornerstones of treatment. Whether different ACE-inhibitors have distinct kidney protective effects is unknown; it is therefore hypothesized that renal diets and enalapril or benazepril have different beneficial effects in proteinuric CKD dogs. Forty-four dogs with proteinuric CKD (IRIS stages 1-4) were enrolled in the study and were fed renal diet for 30 days. Thereafter, they were randomly assigned to one of 2 groups. Dogs in group A (n=22) received enalapril (0.5 mg/kg, q12h) and in group B (n=22) benazepril (0.5 mg/kg, q24h); in both groups, dogs were fed the same renal diet. After randomization, dogs were monitored for 120 days. Body weight and body condition score (BCS), serum concentrations of creatinine, blood urea nitrogen (BUN), albumin and total proteins, and urine protein-to-creatinine (UPC) ratio were compared at different time-points. After 30 days of renal diet, creatinine, BUN and UPC ratio decreased significantly (p<0.0001). Compared to randomization, body weight, BCS, albumin, total proteins, creatinine and BUN did not vary during follow-up in the 44 dogs and differences between group A and B were not observed. However, the UPC ratio of group A at day 60, 90 and 150 was significantly lower than in group B and compared to randomization (p<0.05). In group B it did not vary overtime. It is concluded that the renal diet is beneficial to decrease creatinine, BUN and UPC ratio in proteinuric CKD dogs. Enalapril further ameliorates proteinuria if administered along with renal diet.

The effect of inter-laboratory variability on the protein:creatinine (UPC) ratio in canine urine

Quantification of proteinuria is a fundamental step in staging dogs with chronic kidney disease and in monitoring the course of disease or the efficacy of anti-proteinuric treatments. Analytical precision and accuracy of the proteinuria assessment could be affected by several factors such as biological variability, different operators and quality control materials. The aim of this study was to assess whether inter-laboratory variability could affect the urinary protein to creatinine (UPC) ratio and whether this variability may affect patient classification according to the International Renal Interest Society (IRIS) sub-staging system. The same urine samples were analysed in three different laboratories using different instruments and different reagent brands.The results of the three laboratories were highly correlated to each other although urinary protein (UP), urinary creatinine (UC) and the UPC ratio of one laboratory were found to be significantly higher than those of the other two. No significant differences between the other two laboratories were recorded. The concordance in classifying dogs according to the IRIS guidelines was good if all three proteinuria categories were analysed separately or if borderline proteinuric (BP) dogs were included in the proteinuric group, and very good if BP dogs were merged into the non-proteinuric group. The inter-laboratory variability in UPC ratio measurement was not so great as to impede the identification of proteinuric dogs, but may influence the estimation of the magnitude of proteinuria.