Search

Background and objectives: No large, randomized, double-blind trials in children with proteinuria treated with angiotensinconverting enzyme inhibitors or angiotensin receptor blockers have previously been reported. Design, setting, participants, & measurements: This 12-week, double-blind, multinational study investigated the effects of losartan 0.7 to 1.4 mg/kg per day compared with placebo (normotensive stratum) or amlodipine 0.1 to 0.2 mg/kg per day up to 5 mg/d (hypertensive stratum) on proteinuria (morning-void urinary protein-creatinine ratio, baseline >0.3 g/g) in 306 children up to 17 years of age. Results: Twelve weeks of treatment with losartan significantly reduced proteinuria compared with amlodipine/placebo: losartan 35.8% (95% confidence interval: 27.6% to 43.1%) versus amlodipine/placebo 1.4% (95% confidence interval: 10.3% to 14.5%), P < 0.001. Significance remained after adjustment for differences across treatment groups in change in BP (losartan produced incremental systolic and diastolic BP reductions versus amlodipine of 5.4 and 4.6 mmHg, respectively; and versus placebo of 3.8 and 4.0 mmHg, respectively). Proteinuria reduction was consistently observed in the normotensive (34.4% losartan; 2.6% placebo) and hypertensive (41.5% losartan; 2.4% amlodipine) strata, and in all prespecified subgroups, including age, gender, race, Tanner stage, weight, prior therapy with angiotensin-converting enzyme inhibitors or angiotensin receptor blockers, as well as among the most common etiologies of proteinuria. Adverse event incidence was low and comparable in all groups. Conclusions: Losartan significantly lowered proteinuria and was well tolerated after 12 weeks in children aged 1 to 17 years with proteinuria with or without hypertension, a population that has not previously been rigorously studied. Clin J Am Soc Nephrol 5: 417–424, 2010. doi: 10.2215/CJN.06620909

Eicosapentaenoic acid (EPA), which is purified from fish oil, attenuates inflammatory responses by decreasing eicosanoid and cytokine production. EPA reportedly improves renal survival in patients with immunoglobulin (Ig)A nephropathy; however, this is unconfirmed. We studied the effects of EPA on IgA nephropathy patients. Eighteen biopsy-confirmed IgA nephropathy patients (aged 31 +/- 3 years) were enrolled. The prognoses based on glomerular findings were good (N = 5), relatively poor (N = 12), and poor (N = 1). EPA was administered at 1.8 g/day for 12 months. Five biopsy-confirmed IgA nephropathy patients were enrolled as control subjects. Administration of other drugs used to treat IgA nephropathy was not changed. The estimated creatinine clearance (eCCr), serum creatinine (Cr) concentration, urinary protein creatinine ratio (U/P), and other clinical parameters were checked. In the EPA group, the Cr went from 0.8 +/- 0.2 mg/dL to 0.7 +/- 0.2 mg/dL after 12 months of EPA treatment, and the U/P went from 550 +/- 580 mg/g Cr to 330 +/- 920 mg/g Cr. The values did not differ significantly; however, Cr and U/P tended to improve, with no adverse effects from the EPA. The eCCr improved significantly (99 +/- 7-110 +/- 8 mL/min, P = 0.001) in the EPA group, but not in the control group (126 +/- 12-120 +/- 13, P > 0.05). The effect of EPA in patients with IgA nephropathy is not pronounced, but these results suggest that EPA is a safe and worthwhile supplement to the drugs used to treat this disease.

Background: We recently reported that immunoreactivity of intrarenal angiotensinogen (AGT) is significantly increased in IgA nephropathy patients. Meanwhile, we have developed direct enzyme-linked immunosorbent assays to measure plasma and urinary AGT (UAGT) in humans. This study was performed to test the hypothesis that UAGT levels are increased in chronic glomerulonephritis patients. Methods: We analyzed 100 urine samples from 70 chronic glomerulonephritis patients (26 from IgA nephropathy, 24 from purpura nephritis, 8 from lupus nephritis, 7 from focal segmental glomerulosclerosis, and 5 from non-IgA mesangial proliferative glomerulonephritis) and 30 normal control subjects. Results: UAGT–creatinine ratio (UAGT/UCre) was correlated positively with diastolic blood pressure (p = 0.0326), urinary albumin–creatinine ratio (p < 0.0001), urinary protein–creatinine ratio (p < 0.0001) and urinary occult blood (p = 0.0094). UAGT/UCre was significantly increased in chronic glomerulonephritis patients not treated with renin-angiotensin system (RAS) blockers compared with control subjects (p < 0.0001). Importantly, glomerulonephritis patients treated with RAS blockers had a marked attenuation of this augmentation (p = 0.0021). Conclusion: These data indicate that UAGT are increased in chronic glomerulonephritis patients and treatment with RAS blockers suppressed UAGT. The efficacy of RAS blockade to reduce the intrarenal RAS activity can be confirmed by measurement of UAGT in chronic glomerulonephritis patients.

The aim of this trial was to evaluate the effectiveness and safety of miltefosine-allopurinol combination therapy vs. the current reference combination therapy, meglumine antimoniate-allopurinol, for canine leishmaniosis. Dogs included in the study exhibited clinical signs of the disease, were positive by PCR and serologically positive by immunofluorescent antibody test for leishmaniosis, and negative for ehrlichiosis. Dogs were divided into two groups: Group 1 was treated with 2 mg/kg of miltefosine orally once daily for 28 days and 10 mg/kg of allopurinol orally twice daily for 7 months; Group 2 was treated with 50 mg/kg of meglumine antimoniate sub-cutaneously twice daily for 28 days and allopurinol (same dose as Group 1) for 7 months. Dogs were examined according to the following schedule: pre-inclusion, Day 0 (D0), D14, D28, D84, D140 and D196. At each visit, blood, urine and bone marrow samples were collected. Parameters monitored included haematology, biochemistry, protein electrophoresis, serology, urinary protein/creatinine ratio and RTQ-PCR performed on bone marrow aspirates. A significant reduction in total clinical score and parasite load was observed in both groups over the 7-month study period (P < 0.0001), with no significant difference between groups (P = 0.3). The safety of miltefosine-allopurinol combination therapy was confirmed by lack of effect on renal and hepatic parameters and adverse reactions. Miltefosine, in combination with allopurinol, offers a safe, convenient and effective alternative treatment option for canine leishmaniosis compared to the reference therapy.

Background/Aims: The purpose of this study was to examine whether tacrolimus is effective and safe, and to determine the optimal dose of tacrolimus for maintenance treatment in patients with lupus nephritis (LN). Methods: A total of 17 adult patients (1 man and 16 women) with LN were enrolled. Tacrolimus was initiated at a dose of 3 mg/day which was administered once per day after the evening meal. Prospective data on renal response and serologic lupus activity were collected and followed for a year. Results: Mean age at baseline was 48.8 ± 12.6 years (range 31–72 years). The mean urinary protein/creatinine ratio significantly decreased from 1.14 ± 1.74 at baseline to 0.23 ± 0.47 at 1 year (p < 0.05). Mean serum C3 significantly increased from 73.0 ± 12.3 mg/dl at baseline to 84.7 ± 12.2 mg/dl at 1 year (p < 0.01). Mean serum creatinine levels were unchanged after tacrolimus treatment. The mean blood concentration of tacrolimus was 3.9 ± 2.1 ng/ml. There was no relationship between the incidence of adverse effects and blood tacrolimus level. Conclusion: Our results suggest tacrolimus to be potentially effective and safe for maintenance treatment in patients with LN.

Objectives Combination therapy with angiotensin II Type I receptor blocker 50 mg of losartan and a fixed combination of losartan (50 mg)/hydrochlorothiazide (12.5 mg) was administered to hypertensive patients with Stage 3 - 4 chronic kidney disease to investigate its renoprotective effect. Methods Subjects already being administered the angiotensin I-converting enzyme inhibitor enalapril and losartan 100 mg daily were enrolled in this open-labeled trial (n = 40). Administration of 100 mg losartan twice daily was replaced with losartan (50 mg)/hydrochlorothiazide (12.5 mg) once daily after the morning meal and losartan at 50 mg once daily after the evening meal for the 24-week study period. Results The mixture of losartan/hydrochlorothiazide significantly reduced systolic and diastolic blood pressures by 14.7 and 7.4 mmHg, respectively, compared with the baseline values. No significant changes were observed in the serum creatinine levels and estimated glomerular filtration rate. The urinary protein/creatinine ratio was, however, significantly decreased. Similarly, the regression line of 1/serum creatinine level was significantly increased after administration of losartan/hydrochlorothiazide. None of the patients exhibited a significant increase in the occurrence of adverse effects. Conclusions Our results demonstrated that a low dose of hydrochlorothiazide had a renoprotective effect due to its blood pressure-lowering effect. We accordingly propose that a low dose of hydrochlorothiazide should be administered to those patients in whom the blood pressure is not well controlled by intensive renin-angiotensin system inhibition therapy using the maximum recommended doses of angiotensin II Type I receptor blockers and angiotensin I-converting enzyme inhibitors.

We reported previously that urinary angiotensinogen (UAGT) levels provide a specific index of the intrarenal renin-angiotensin system (RAS) status in angiotensin II–dependent hypertensive rats. To study this system in humans, we recently developed a human angiotensinogen ELISA. To test the hypothesis that UAGT is increased in hypertensive patients, we recruited 110 adults. Four subjects with estimated glomerular filtration levels 2 were excluded because previous studies have already shown that UAGT is highly correlated with estimated glomerular filtration in this stage of chronic kidney disease. Consequently, 106 paired samples of urine and plasma were analyzed from 70 hypertensive patients (39 treated with RAS blockers [angiotensin-converting enzyme inhibitors or angiotensin II type 1 receptor blockers; systolic blood pressure: 139±3 mm Hg] and 31 not treated with RAS blockers [systolic blood pressure: 151±4 mm Hg]) and 36 normotensive subjects (systolic blood pressure: 122±2 mm Hg). UAGT, normalized by urinary concentrations of creatinine, were not correlated with race, gender, age, height, body weight, body mass index, fractional excretion of sodium, plasma angiotensinogen levels, or estimated glomerular filtration. However, UAGT/urinary concentration of creatinine was significantly positively correlated with systolic blood pressure, diastolic blood pressure, urinary albumin:creatinine ratio ( r =0.5994), and urinary protein:creatinine ratio ( r =0.4597). UAGT/urinary concentration of creatinine was significantly greater in hypertensive patients not treated with RAS blockers (25.00±4.96 μg/g) compared with normotensive subjects (13.70±2.33 μg/g). Importantly, patients treated with RAS blockers exhibited a marked attenuation of this augmentation (13.26±2.60 μg/g). These data indicate that UAGT is increased in hypertensive patients, and treatment with RAS blockers suppresses UAGT, suggesting that the efficacy of RAS blockade to reduce the intrarenal RAS activity can be assessed by measurements of UAGT.

Although immune-mediated pathogenesis in adriamycin (ADR)-induced nephropathy has been proposed recently, studies are lacking about the effects of immunmodulators, such as vitamin D, on ADR-induced nephrotoxicity. We hypothesized that vitamin D(3) (cholecalciferol) would be beneficial on ADR-induced nephropathy because of its immunmodulatory properties. Eighteen male Wistar rats were divided into three groups (n = 6): group 1 (control), group 2 (single ADR injection intravenously), and group 3 (similar single ADR injection intravenously + daily oral cholecalciferol for 21 days) were used in the study. A single high dose of ADR resulted in increased urinary protein: creatinine ratio for all three weeks of the experiment in both groups 2 and 3 compared with the controls. Histological examination of the kidney tissue revealed distinct tubular lesions as tubular necrosis, hyaline casts in tubular lumen, tubular degeneration, tubular dilatation, and tubular vacuolization in group 2 compared with group 1. These tubular lesions were significantly reduced in group 3 compared to group 2. The results of this study indicate that cholecalciferol causes satisfactory tubulointerstitial recovery in ADR-induced nephrotoxicity in rats.

Background. The benefits of steroid therapy in immunoglobulin A nephropathy (IgAN) have not been established. Methods. The effect of steroids on kidney survival was retrospectively investigated in 702 patients with IgAN by multivariate analyses. Results. There were 295 men and 407 women. The median follow-up period was 62 months. One hundred and ninety-four patients were treated with oral steroids (oral steroid group). Thirty-four patients were treated with methylprednisolone (mPSL) pulse therapy (pulse steroid group) followed by oral prednisolone (PSL). In 474 patients, no steroid was used (no steroid group). The urinary protein-creatinine ratio and histological grade were significantly different among treatment groups and were highest in the pulse steroid group followed by the oral steroid group and lowest in the no steroid patients. Serum creatinine was significantly higher in the pulse steroid group than in other two groups. Eighty-five patients developed end-stage renal failure (ESRF) requiring haemodialysis. In multivariate analysis, steroid pulse therapy significantly decreased the risk of ESRF while oral steroid treatment did not improve renal survival in this cohort. Conclusion. We found that pulse steroid therapy improved kidney survivals in IgAN. Since the clinical findings and histological grade were the most severe in patients treated with mPSL pulse therapy, such therapy may prevent progression of IgAN.

Tyrosinaemia type I (TTI) is an inherited deficiency in the enzyme fumarylacetoacetate hydrolase and is frequently complicated by renal tubular dysfunction which may persist in some patients after hepatic transplantation. Nitisinone has revolutionized the management of TTI but its effect on renal tubular dysfunction has not been described in a large cohort of patients.To document the incidence and progression of renal tubular dysfunction in children with TTI treated with nitisinone at a single centre.Twenty-one patients with TTI from a single centre were treated with nitisinone for at least 12 months. Median age at first treatment was 17 weeks (range 1 week to 27 months). Nine patients (43%) presented in acute liver failure, seven (33%) had a chronic presentation and five (24%) were detected pre-clinically.A retrospective case analysis of plasma phosphate, urinary protein/creatinine ratio and tubular reabsorption of phosphate was performed for all patients as markers of tubular function. Renal ultrasounds were examined for evidence of nephrocalcinosis and where available, skeletal radiographs for rickets.All patients had biochemical evidence of renal tubular dysfunction at presentation. After nitisinone and dietary treatment were started, all three markers normalized within one year. Four children had clinical rickets at presentation (which improved), of whom one had nephrocalcinosis, which did not reverse on nitisinone. No child redeveloped tubular dysfunction after commencing nitisinone. All patients with TTI had evidence of tubular dysfunction at presentation and in all cases this resolved with nitisinone and dietary control.The tubulopathy associated with TTI is reversible.

Background. The current treatment regimes for patients with nephrotic syndrome due to idiopathic membranous nephropathy (MN) and focal segmental glomerulosclerosis (FSGS) are based on steroids and/or cytotoxic agents. Data on the effect of mycophenolate mofetil (MMF) for these conditions are scarce and confounding. Methods. We compared the efficacy of an MMF-based therapy with standard therapies in inducing remission in adult nephrotics with MN and FSGS in a randomized pilot study. MMF was given at 2g/day for 6 months along with prednisolone at 0.5mg/kg/day for 2–3 months. Conventional therapy was prednisolone 1mg/kg/day for 3–6 months for FSGS and alternating monthly cycles of steroids and cyclophosphamide for 6 months for MN. The primary end point was change in urinary protein/creatinine ratio. Results. A total of 54 patients (21 MN and 33 FSGS) were recruited; 28 were randomized to receive MMF (group A) and 26 were on conventional treatment (group B). There was no difference in the proportion of patients achieving remission in two groups (64 and 80% in MN and 70 and 69% in FSGS). The frequency of relapses and incidence of infections was also similar. FSGS patients in group A achieved remission faster and received a lower cumulative steroid dose. Conclusions. A 6-month treatment with MMF is as effective as the conventional treatment for primary treatment of MN and FSGS in the short term. It induces remission faster andreducessteroidexposureinFSGSpatients.Studieswith more cases and longer follow-up are required to evaluate its impact on preservation of kidney function.

The objective of the current work is to report the preliminary experience with tacrolimus (TL) administered as a single-dose daily for maintenance therapy of young patients with pediatric-onset, long-standing systemic lupus erythematosus (SLE). Six consecutive patients with long-standing SLE were recruited for a 6-month open-label trial of single-dose-daily administration of tacrolimus (3 mg/day) without dose up of concomitantly administered prednisolone (PDN). TL treatment was started at the time of the most recent flares. Data on the clinical and serologic lupus activity were collected prospectively. The baseline characteristics of the patients were: mean age, 20 years; urinary protein/creatinine ratio, 1.22 ± 1.94; serum C3 level, 70.8 ± 21.2 (normal, 79—152 mg/dL); serum complement hemolytic activity (CH50), 22.2 ± 10.3 (normal, 23—46 U/mL); serum anti-dsDNA antibody titer, 60.4 ± 71.7 IU/mL (normal, < 12.0 IU/mL); serum creatinine, 0.55 ± 0.11 mg/dL; European Consensus Lupus Activity Measurement (ECLAM) index, 5.2 ± 2.6. Despite the gradual tapering of the PDN dose, marked improvement as compared with the baseline values was observed in the ECLAM index examined at one and three months and serological parameters examined at three months after the start of treatment. After a 6-months' therapy, complete response was achieved in all of the patients (serum CH50 value, 27.7 ± 8.3 U/mL; serum anti-dsDNA antibody titer, 28.4 ± 27.9 U/mL and the ECLAM index, 1.2 ± 1.2 ( P < 0.05), respectively), except in one patient who showed WHO class V lupus nephritis. No serious adverse effects were observed. These data suggest that TL, even when administered as a single-daily dose, is effective and safe for selected young patients with pediatric-onset, long-standing SLE. However, further studies on a larger number of patients are needed to confirm these results. Lupus (2007) 16, 896—900.

The phospholipase A2 receptor (PLA2R1) is the major autoantigen in idiopathic membranous nephropathy. However, the value of anti-PLA2R1 antibody titers in predicting patient outcomes is unknown. Here, we screened serum samples from 50 patients positive for PLA2R1 for immunoreactivity against a series of PLA2R1 deletion mutants covering the extracellular domains. We identified reactive epitopes in the cysteine-rich (CysR), C-type lectin domain 1 (CTLD1), and C-type lectin domain 7 (CTLD7) domains and confirmed the reactivity with soluble forms of each domain. We then used ELISAs to stratify 69 patients positive for PLA2R1 by serum reactivity to one or more of these domains: CysR (n=23), CysRC1 (n=14), and CysRC1C7 (n=32). Median ELISA titers measured using the full-length PLA2R1 antigens were not statistically different between subgroups. Patients with anti-CysR–restricted activity were younger (P=0.008), had less nephrotic range proteinuria (P=0.02), and exhibited a higher rate of spontaneous remission (P=0.03) and lower rates of renal failure progression (P=0.002) and ESRD (P=0.01) during follow-up. Overall, 31 of 69 patients had poor renal prognosis (urinary protein/creatinine ratio >4 g/g or eGFR

A 9-year-old boy presented with a 1-day history of a palpable purpuric rash on his lower limbs 3 days after a viral illness. One week later, he developed arthralgia in his lower limbs, facial oedema and progression of the rash to his buttocks and lower arms. He did not present with any abdominal pain, blood pressure was 131/79 mm Hg and urinary protein:creatinine ratio was 183 mg/mmol with normal blood tests. …

Chronic kidney disease (CKD) is a global public health problem. Currently, as for advanced CKD populations, medication options limited in angiotensin-converting enzyme inhibitors (ACEi) and angiotensin receptor blockers (ARB), which were partially effective. A Chinese herbal compound, Bupi Yishen formula, has showed renal protective potential in experiments and retrospective studies. This study will evaluate the efficacy and safety of Bupi Yishen formula (BYF) in patients with CKD stage 4. In this double blind, double dummy, randomized controlled trial (RCT), there will be 554 non-diabetes stage 4 CKD patients from 16 hospitals included and randomized into two groups: Chinese medicine (CM) group or losartan group. All patients will receive basic conventional therapy. Patients in CM group will be treated with BYF daily while patients in control group will receive losartan 100 mg daily for one year. The primary outcome is the change in estimated glomerular filtration rate (eGFR) over 12 months. Secondary outcomes include the incidence of endpoint events, liver and kidney function, urinary protein creatinine ratio, cardiovascular function and quality of life. This study will be the first multi-center, double blind RCT to assess whether BYF, compared with losartan, will have beneficial effects on eGFR for non-diabetes stage 4 CKD patients. The results will help to provide evidence-based recommendations for clinicians. Chinese Clinical Trial Registry Number: ChiCTR-TRC-10001518 .

The urinary protein/creatinine ratio [Up/Ucr (g/gCr)] has been used in the clinical management of patients with chronic kidney disease (CKD). However, a discrepancy is often noted between the Up/Ucr and 24-h urinary protein excretion [24hUp (g/day)] in patients with extremes of muscle mass. We examined devised a method for precise estimation of the 24-h urinary protein excretion (E-24hUp) based on estimation of 24-h urinary creatinine output (E-24hCr).Three parameters, spot Up/Ucr, 24hUP and E-24hUp (=Up/Ucr × E-24hCr), were determined in 116 adult patients with CKD. The correlations among the groups were analyzed.There was a significant correlation between the Up/Ucr and 24hUp (p 0.001). We divided the patients into three groups according to the 24hUp; the low urinary protein group (1.0 g/day), the intermediate urinary protein group (1.0-3.5 g/day), and the high urinary protein group (3.5 g/day). There was a significant correlation between the Up/Ucr and 24hUp in the low (p = 0.04) and high urinary protein (p = 0.01) groups, whereas the correlation coefficient was lower in the intermediate urinary protein (p = 0.07) group. Thus, we found a significant correlation between 24hUp and E-24hUp in the study population overall (p 0.001), in the low (p = 0.01), in the intermediate (p 0.001), and in the high urinary protein group (p 0.001).We conclude that a poor correlation exists between the Up/Ucr and 24hUp in patients with intermediate urinary protein excretion levels. The recommended parameter for monitoring proteinuria in such patients may be the E-24hUp, which is calculated using the E-24hCr.

Although the value of testing for proteinuria may be undisputed and understood by nephrologists and diabetologists, the lack of clarity about the rationale for testing and the optimal way of doing so in primary care has caused confusion for many practitioners.1 Issues such as variation in proteinuria definition, laboratory measurement, and reporting methods, along with conflicting messages about who, how, and when to test, have led to uncertainty and under-testing.1,2 There have been long-standing debates about the use of various dipsticks, the role of proteinuria in urinary tract infection, the use of urinary protein:creatinine ratio (PCR) versus albumin:creatinine ratio (ACR), and the number of tests needed for identification versus quantification of proteinuria. Reporting variations include some laboratories using non-numeric results such as ‘ratio too low to calculate’ making visualisation of results and accurate audit of ACR testing challenging for busy practitioners. Urinary dipsticks have important limitations in terms of their accuracy in detecting and quantifying albuminuria.3 In this context, GPs and other clinicians could be forgiven for being uncertain about the clinical utility of its identification. Chronic kidney disease (CKD) has been included in the Quality and Outcomes Framework (QOF) since 2006–2007, and, from 2009–2010, included a proteinuria indicator (‘The percentage of patients on the CKD register whose notes have a record of a urine albumin:creatinine ratio [or protein:creatinine ratio] test in the preceding 12 months’). Currently, several CKD indicators are in the process of being ‘retired’, including the one relating to proteinuria testing. This increases the potential for uncertainty about the role of proteinuria testing and is likely to lead to a fall in ACR tests in England, particularly in people without diabetes, unless it is seen as valuable in its own right. It may also serve to reinforce the suggestion that labelling people …

Because systemic lupus erythematosus (SLE) affects women of reproductive age, pregnancy is a major concern.To identify predictors of adverse pregnancy outcomes (APOs) in patients with inactive or stable active SLE.Prospective cohort.Multicenter.385 patients (49% non-Hispanic white; 31% with prior nephritis) with SLE in the PROMISSE (Predictors of Pregnancy Outcome: Biomarkers in Antiphospholipid Antibody Syndrome and Systemic Lupus Erythematosus) study. Exclusion criteria were urinary protein-creatinine ratio greater than 1000 mg/g, creatinine level greater than 1.2 mg/dL, prednisone use greater than 20 mg/d, and multifetal pregnancy.APOs included fetal or neonatal death; birth before 36 weeks due to placental insufficiency, hypertension, or preeclampsia; and small-for-gestational-age (SGA) neonate (birthweight below the fifth percentile). Disease activity was assessed with the Systemic Lupus Erythematosus Pregnancy Disease Activity Index and the Physician's Global Assessment (PGA).APOs occurred in 19.0% (95% CI, 15.2% to 23.2%) of pregnancies; fetal death occurred in 4%, neonatal death occurred in 1%, preterm delivery occurred in 9%, and SGA neonate occurred in 10%. Severe flares in the second and third trimesters occurred in 2.5% and 3.0%, respectively. Baseline predictors of APOs included presence of lupus anticoagulant (LAC) (odds ratio [OR], 8.32 [CI, 3.59 to 19.26]), antihypertensive use (OR, 7.05 [CI, 3.05 to 16.31]), PGA score greater than 1 (OR, 4.02 [CI, 1.84 to 8.82]), and low platelet count (OR, 1.33 [CI, 1.09 to 1.63] per decrease of 50 × 109 cells/L). Non-Hispanic white race was protective (OR, 0.45 [CI, 0.24 to 0.84]). Maternal flares, higher disease activity, and smaller increases in C3 level later in pregnancy also predicted APOs. Among women without baseline risk factors, the APO rate was 7.8%. For those who either were LAC-positive or were LAC-negative but nonwhite or Hispanic and using antihypertensives, the APO rate was 58.0% and fetal or neonatal mortality was 22.0%.Patients with high disease activity were excluded.In pregnant patients with inactive or stable mild/moderate SLE, severe flares are infrequent and, absent specific risk factors, outcomes are favorable.National Institutes of Health.

Mice selected on the basis of an acute inflammatory response (AIR) can provide information about the immunopathological mechanisms of glomerulonephritis. We studied the differences between mice selected for a maximal AIR (AIRmax that attract more polymorphonuclear cells to the site of injury) or a minimal AIR (AIRmin that attract more mononuclear cells) in an experimental model of IgA nephropathy in order to investigate the effect of genetic background on glomerular disease progression and the participation of the monocyte chemoattractant protein-1 (MCP-1) chemokine. IgA nephropathy was induced by intraperitoneal ovalbumin injection and bile duct ligation in AIRmax and AIRmin mice. Histological changes, urinary protein/creatinine ratio, serum IgA levels, immunofluorescence for IgA, IgG and complement C3 fraction, immunohistochemistry for macrophages and MCP-1, and MCP-1 levels in macerated kidney were determined. Mesangial IgA deposition was seen only in AIRmin mice, which presented more renal lesions. Increased serum IgA levels (1.5 +/- 0.4 vs 0.3 +/- 0.1 mg/mL, P0.001), high glomerular MCP-1 expression and decreased monocyte/macrophage infiltration in the interstitial area (0.3 +/- 0.3 vs 1.1 +/- 0.9 macrophages/field, P0.05) were detected in AIRmin mice compared to AIRmax mice. No glomerular monocyte/macrophage infiltration was detected in either strain. In spite of the absence of IgA deposition, AIRmax mice presented discrete or absent mesangial proliferation. The study showed that there are differences between mice selected for AIRmax and AIRmin with respect to serum IgA levels, histological damage and MCP-1 chemokine production after ovalbumin injection in combination with bile duct ligation.

Whereas the diurnal fall of BP (dipping) is an important prognostic marker in patients with chronic renal failure (CRF), the integrity of physiologic ultradian (i.e., shorter than 24 h) cardiovascular rhythms in patients with CRF is unknown. Also, the relationship between conventional dipping analysis and Fourier spectral rhythm analysis has not been examined in renal hypertension. The prevalence and dimensions of the circadian and three ultradian (12, 8, and 6 h) cardiovascular rhythms were studied by ambulatory BP monitoring in 214 children (aged 3 to 18 yr) with CRF (stage 2 to 4 chronic kidney disease) and no antihypertensive treatment compared with 938 healthy control subjects, and the relationship of rhythm characteristics to conventional dipping parameters, renal function, proteinuria, and serum electrolytes was assessed. The CRF cohort exhibited significantly reduced amplitudes of the circadian and all ultradian cardiovascular rhythms studied (all P < 0.01). Moreover, all BP and most heart rate rhythms showed significantly delayed acrophases (time of peak; P < 0.01). Whereas conventional BP dipping parameters (day/night difference, day/night ratio) and the 24-h BP amplitude were independent of renal function, the 8-h BP amplitude was positively correlated with GFR (r = 0.3, P = 0.01) and inversely correlated with the urinary protein/creatinine ratio (r = -0.27, P < 0.05), and the 6-h BP amplitude was inversely correlated with proteinuria (r = -0.3, P < 0.02). Children who displayed 24- or 12-h cardiovascular rhythms had significantly lower serum calcium levels than children without these rhythms. In summary, children with CRF display not only blunted circadian but also blunted ultradian cardiovascular rhythms. Ultradian but not circadian rhythms or conventional dipping parameters are quantitatively associated with renal function and proteinuria.

About 85–90% of children with idiopathic nephrotic syndrome responds to steroid therapy while the remaining 10–15% fails to respond and is defined as steroid-resistant nephrotic syndrome (SRNS). The histopathological lesions in SRNS are minimal changes, focal and segmental sclerosis (FSGS) and mesangial proliferation. The response to cyclosporine alone or in combination with prednisolone therapy is variable. Proteinuria in FSGS in some patients is associated with a permeability factor (PF). Galactose has been shown to bind with PF [1] and prevents its interaction with podocyte glycocalyx, and oral administration of galactose may lead to reduction of proteinuria [2]. In view of this, we report an observational case study where two separate courses of oral galactose were given to three children with steroid-resistant idiopathic nephrotic syndrome with FSGS in order to reduce proteinuria and increase serum albumin levels. The patient characteristics are presented in Table ​Table1.1. They had generalized oedema, urinary protein/creatinine ratio of >200 mg/mmol (>2 mg/mg), hypalbuminaemia serum albumin 5.18 mmol/L (>200 mg/dL). The children did not achieve remission with prednisolone (2 mg/kg/day) therapy administered for 4 weeks. Kidney biopsy tissues, examined in light and immunofluorescent microscopy, demonstrated focal and segmental glomerulosclerosis. The patients were tested for C3, C4, ANA, anti-ds DNA, HIV, Hepatitis B surface antigen and tuberculin test. Chest radiographs were normal. NPHS2 gene analysis showed R229Q polymorphism in Case 1. The protocol of the study was approved by the Institute Ethics Committee. Table 1. Patient characteristics The children were treated with cyclosporine (4–5 mg/kg/day in two divided doses), prednisolone (1.5 mg/kg, single dose alternate days with gradual taper to a minimum of 0.5 mg/kg) and ramipril (0.2 mg/kg/day, single dose). Furosemide (1–2 mg/kg/day) was given to reduce oedema. The patients received cyclosporine, prednisolone and ramipril for 11–14 months duration and had stable serum creatinine levels. Doses of cyclosporine and ramipril remained unchanged. Patients did not achieve remission as urine protein/creatinine ratios of >200 mg/mmol (>2 mg/mg) persisted. Thereafter, oral d-galactose (Manufactured by Hi Media Laboratories Pvt. Ltd., Mumbai, India) was added at a dose of 0.2 g/kg/dose, twice daily. The patients were followed regularly at a 30-day interval during the first course of galactose trial given for 90 days. After an interval of 90 days in Case 1, 60 days in Case 2 and 105 days in Case 3, a second course of galactose treatment at the same doses was reinstituted for 30 days. The changes in urinary protein/creatinine ratios and serum albumin levels are shown in Figure 1. In all three patients, urinary protein/creatinine ratios decreased (by 37.9, 50.6 and 77.5%), and serum albumin levels increased (by 56, 72 and 23.3%) at 90 days from their pre-galactose values. After discontinuation of galactose, urine protein/creatinine and serum albumin values showed deterioration at 120 days. After the second course of galactose, there was again a reduction of urinary protein/creatinine ratios by 46.5% in Case 1, 37.5% in Case 2 and 25.7% in Case 3 and an increase in serum albumin levels in comparison to their values 30 days before. However, parameters became again abnormal after discontinuation of galactose. No adverse events were noted following galactose therapy. Fig. 1 Urine protein/creatinine ratios and serum albumin levels during the two periods of galactose therapy and the interval period. It showed gradual reduction in urine protein/creatinine ratios and rise in serum albumin values during, deterioration after discontinuation ... The galactose had a beneficial effect in all three patients. The galactose helps in reduction of proteinuria as it directly binds with PF and prevents interaction of PF to galactose residues of podocyte glycocalyx. Subsequently, the galactose–PF complex is cleared from plasma by hepatocytes or macrophages [2]. De Smet et al. [3] in one adult and Kopac et al. [4] demonstrated the effect of galactose in reduction of proteinuria and its benefit persisted for about 3 months in one case. In our cases, the effect lasted as long as galactose was given; indicating that a continuous treatment is necessary to maintain its positive effect on proteinuria. Our patients had no remission with cyclosporine and prednisolone therapy given for a sufficient period. Galactose had lead to reduction of proteinuria and increase in serum albumin during the treatment period. Recently, Sgambat et al. [5] observed no significant difference between pre- and post-treatment mean urine protein/creatinine ratios after 16 weeks of galactose administration, and the authors concluded that it failed to improve proteinuria. In our study, though no patient achieved complete remission (urine protein/creatinine ratio

To determine prospectively in hypertensive pregnant women 1) the accuracy of dipstick testing for proteinuria using automated urinalysis, 2) factors that might affect such accuracy, and 3) the potential impact of automated dipstick testing on the accuracy of diagnosis of preeclampsia according to acceptance of proteinuria at either 1 + or 2 + level.Prospective study.Antenatal day assessment unit and antenatal ward of St George Hospital, a teaching hospital in Sydney, Australia.170 hypertensive pregnant women attending as outpatients or inpatients.503 midstream urine samples were collected prospectively on separate occasions from 170 women. Full urinalysis was recorded using the Bayer Clinitek 50 automated urinalysis device and Multistix 10SG urinalysis strips (Bayer Diagnostics, Victoria, Australia). Each MSU was analysed for spot protein/creatinine ratio and also for culture and sensitivity if symptoms of a urinary tract infection were present or dipstick included positive nitrites. Urinalysis protein results were compared with spot urinary protein/creatinine ratio (previously shown to correlate with 24-hr urine protein excretion) to determine the accuracy of urinalysis. True proteinuria was defined as a ratio/= 30 mg protein/mmol creatinine.False positive dipstick tests ranged from 7% at 3 + level to 71% at 1 + proteinuria level while false negative rates were 7% for "nil" and 14% for "trace" proteinuria, 9% overall. Accepting the dipstick proteinuria result at face value led to an incorrect diagnosis of preeclampsia or gestational hypertension in 85 (50%) women. Dipstick proteinuria was significantly more likely to be correct (true positive/true negative) if diastolic blood pressure was elevated90 mmHg (p = 0.032) and in the absence of ketonuria (p = 0.001). Accepting a diagnosis of preeclampsia on the basis of de novo hypertension and dipstick testing alone was accurate less often (70%) when1 + was used as a discriminant value than at the 82% of presentations when2 + was used (p = 0.001).Accepting "nil" or "trace" proteinuria as a true negative dipstick results fails to identify approximately 1 in 11 hypertensive pregnant women with true proteinuria, a false negative rate that may be acceptable provided these women are subject to ongoing vigilant clinical review. Even with automated urinalysis the false positive rate for dipstick levels/= 1 + is very high, particularly in the presence of ketonuria and relying on this alone to diagnose preeclampsia leads to significant errors in diagnosis. Accepting/= 2 + dipstick proteinuria improves overall diagnostic accuracy for preeclampsia at the expense of a higher false negative rate. This study emphasizes the need to confirm dipstick proteinuria with a further test such as a spot urine protein/creatinine ratio in all hypertensive pregnant women, particularly in research studies.

Submitted by Guilherme Lemeszenski (guilherme@nead.unesp.br) on 2013-08-22T18:58:04Z No. of bitstreams: 1 S0102-86502003000400010.pdf: 2414096 bytes, checksum: d7220cc3a262b08179698fb898b4e679 (MD5) Made available in DSpace on 2013-08-22T18:58:04Z (GMT). No. of bitstreams: 1 S0102-86502003000400010.pdf: 2414096 bytes, checksum: d7220cc3a262b08179698fb898b4e679 (MD5) Previous issue date: 2003-08-01 Made available in DSpace on 2013-09-30T19:53:27Z (GMT). No. of bitstreams: 2 S0102-86502003000400010.pdf: 2414096 bytes, checksum: d7220cc3a262b08179698fb898b4e679 (MD5) S0102-86502003000400010.pdf.txt: 21953 bytes, checksum: 779a79ec168ecaffe8c8d7afe04fa537 (MD5) Previous issue date: 2003-08-01 Submitted by Vitor Silverio Rodrigues (vitorsrodrigues@reitoria.unesp.br) on 2014-05-20T13:14:06Z No. of bitstreams: 2 S0102-86502003000400010.pdf: 2414096 bytes, checksum: d7220cc3a262b08179698fb898b4e679 (MD5) S0102-86502003000400010.pdf.txt: 21953 bytes, checksum: 779a79ec168ecaffe8c8d7afe04fa537 (MD5) Made available in DSpace on 2014-05-20T13:14:06Z (GMT). No. of bitstreams: 2 S0102-86502003000400010.pdf: 2414096 bytes, checksum: d7220cc3a262b08179698fb898b4e679 (MD5) S0102-86502003000400010.pdf.txt: 21953 bytes, checksum: 779a79ec168ecaffe8c8d7afe04fa537 (MD5) Previous issue date: 2003-08-01 OBJETIVO: Avaliar a função renal de cães sadios, sob dois protocolos para administração de cisplatina. MÉTODOS: Todos os animais foram submetidos a três sessões de quimioterapia com cisplatina (60mg/m², iv) a intervalos de 21 dias. Foi realizada fluidoterapia com solução de cloreto de sódio a 0,9%, (25mL/kg/hora,iv), durante duas horas e, após administração de cisplatina, por mais uma hora. Os animais do grupo 2 receberam furosemida (2mg/kg, iv) 20 minutos antes da administração da cisplatina. A avaliação da função renal foi feita por exame clinico, urinálise, concentrações séricas de uréia e creatinina, clearance de creatinina, excreção fracionada de sódio e de potássio e razão proteína: creatinina urinária. As avaliações foram feitas imediatamente antes e 1, 2, 5, e 21 dias após cada uma das três sessões de quimioterapia. RESULTADOS: Mantiveram-se dentro da normalidade, não sendo detectados sinais de lesões ou insuficiência renal. Os animais que não receberam furosemida sofreram aumento gradativo nas concentrações séricas de creatinina e diminuição no clearance da mesma. CONCLUSÃO: O regime de fluidoterapia empregado mostra ser efetivo em minimizar a ação nefrotóxica da cisplatina e benefício adicional importante é obtido pela administração de furosemida. PURPOSE: Evaluated the renal function of healthy dogs under two protocols for cisplatin administration. METHODS: All animals were under three chemotherapy sessions with cisplatin (60mg/m², i.v) at 21 days intervals. It was administerd, as fluid therapy, 0,9% sodium chloride solution (25mL/kg/hour, i.v), for two hours and, after cisplatin administration, for more one hour. The animals of the group 2 received furosemide (2mg/kg, i.v.) 20 minutes before the cisplatin administration. The renal function evaluation was made by physical examination, urinalisis, urea and creatinine serum levels, creatinine clearance, sodium and potassium fractional excretions, and urinary protein:creatinine ratio. The evaluations were done imidiatilly before, 1, 2, 5 and 21days after each one of the three chemotherapy sessions. RESULTS: All results were in the interval of normal variation, and no signs of renal damage or failure were detected. The animals that did not recive furosemide showed gradual increment of creatinine serum levels and decreases of the creatinine clearance. CONCLUSIONS: The protocol for fluid therapy seem to be effective in minimize the nephrotoxic action of cisplatin and an addition importante benefit is obtained with furosemide administration. Universidade Estadual Paulista Faculdade de Ciências Agrárias e Veterinárias Departamento de Clínica e Cirurgia Veterinária Universidade Estadual Paulista Faculdade de Ciências Agrárias e Veterinárias Universidade Estadual Paulista Faculdade de Ciências Agrárias e Veterinárias Departamento de Clínica e Cirurgia Veterinária Universidade Estadual Paulista Faculdade de Ciências Agrárias e Veterinárias

Objectives Diagnosis of early feline chronic kidney disease (CKD) is challenging. Glomerular filtration rate (GFR) is the best overall indicator of kidney function, but multisample plasma clearance methods to determine GFR are labour intensive, time consuming and stressful for feline patients. This study aimed to develop simplified methods to detect decreased GFR in cats. Methods Data from a nine-sample combined plasma exogenous creatinine–iohexol clearance test of 73 cats were used. Limited sampling strategies were developed by comparing all sampling time combinations with the complete nine sampling times set and selecting the best sampling time combinations based on maximum relative error. By regression analysis, the ability of routine blood (serum creatinine, serum urea) and urine (urine specific gravity, urinary protein:creatinine ratio) variables to predict GFR or identify cats with low or borderline GFR was examined. Cut-off clearance marker concentrations to predict low or borderline GFR was determined at three time points after marker injection. All procedures were analysed for three clearance markers (exo-iohexol, creatinine, endo-iohexol). Results For reliable estimation of GFR, at least three blood samples for clinical purposes and five blood samples for research purposes are required. Regression formulae based on routine variables did not reliably predict GFR, but accurately identified cats with low (sensitivity 96.5–98.2%; specificity 60–91.3%) or borderline (sensitivity 91.1–96%; specificity 76.5–81.8%) GFR. Clearance marker concentrations exceeding given marker cut-off concentrations also identified cats with low or borderline GFR with high sensitivities and specificities. Conclusions and relevance These simplified methods will facilitate the detection of early kidney dysfunction in cats. Early diagnosis allows timely therapeutic intervention, and future studies must reveal whether this improves the long-term outcome of cats with CKD.

Background: Although there are many available data about renal involvement in patients with beta thalassemia major (TM), the changes in renal functions of other types, such as thalassemia intermedia (TI) and thalassemia minor (TMin), were reported less. Therefore, we aimed to evaluate renal tubular and glomerular functions in patients with three types of beta thalassemia. Methods: This prospective case-control study was conducted on 118 beta-thalassemia patients (49 in TM, 18 in TI and 51 TMin) and 51 healthy controls. Glomerular functions [estimated glomerular filtration rate (GFR), serum cystatin C and urinary protein creatinine ratio] and tubular functions [fractioned sodium excretion (FENa), tubular reabsorption of phosphorus, urinary excretion of uric acid, levels of retinol-binding protein, alpha-1 macroglobulin (alpha-1M), and beta-2 microglobulin, calcium creatinine ratio] were assessed in all patients and controls. Results: The mean ages of the groups and controls at presentation were similar. Although GFR was similar in all patients and control groups, serum levels of cystatin C in patients with TM and TI were significantly higher compared to TMin and controls. Alpha-1M, FENa, urinary excretion of uric acid, and urine protein/creatinine ratio in TM and TI groups were significantly higher than the others. Mean cystatin C level was also higher in patients with TMin compared the controls. However, there were no significant differences according to all tubular and other glomerular functions between TMin and control groups. Conclusions: Although all types of beta thalassemia patients should be closely monitored to prevent further decrease in renal functions, the patients with TI should be considered to have a higher risk of glomerular and tubular deterioration as well as TM. © 2015 © 2015 Taylor & Francis.

Effects of dual blockade of the renin-angiotensin system in primary proteinuric nephropathies.BackgroundBlockade of the renin-angiotensin system (RAS) with angiotensin converting enzyme (ACE) inhibitors or with angiotensin II type 1 (AT1) receptor blockers has been shown to reduce proteinuria and to slow down the progression of renal disease in diabetic and non-diabetic primary proteinuric nephropathies. Additionally, this beneficial effect is not dependent on blood pressure control.MethodsTo assess and compare the effects of lisinopril (up to 40 mg/day), candesartan (up to 32 mg/day) and combination therapy (lisinopril up to 20 mg/day plus candesartan up to 16 mg/day) on urinary protein excretion, 45 patients with primary proteinuric nephropathies (urinary protein/creatinine ratio 3.8 ± 2.4 g/g) and normal or slightly reduced renal function (CCr 95 ± 33 mL/min) were enrolled in a six month multicenter, prospective, open, randomized, active-controlled and parallel-group trial with 1:1:1 allocation. Blood pressure goal was set at or below 125/75 mm Hg for all patients, with additional antihypertensive medication prescribed if required.ResultsRenal function, estimated by creatinine clearance, remained stable throughout the study. Hyperkalemia (K>5.5 mmol/L) was detected in 3.1% of all measurements in follow-up, and was more frequent in patients treated with lisinopril alone or lisinopril plus candesartan (P < 0.001) than in those on candesartan alone. No other relevant adverse event was recorded. The blood pressure goal (

Background: Cilnidipine is a dual blocker of L type and N type calcium channel and dilates both afferent and efferent arterioles. Hence it increases renal blood flow and reduces glomerular pressure ultimately reducing proteinuria. Thus, it may exert renoprotective effects. The present study was designed to compare the antiproteinuric effects of cilnidipine and amlodipine in hypertensive patients with chronic kidney disease as add on therapy to patients on losartan.Methods: This is a randomized, open label, prospective, parallel group study conducted in the out patient Department of Nephrology. The trial enrolled Diabetic CKD patients with hypertension and with spot urine protein creatinine ratio (PCR) ≥0.2 who were being treated with T. Losartan 50mg/day for >2 months. The subjects were then randomly assigned to 2 groups to receive either cilnidipine 10-20mg/day (Group A-46) or amlodipine 5-10mg/day (Group B- 50). The drugs were given for a duration of 6 months for each patient. The dose of losartan (50mg/day) was not adjusted throughout the study.Results: After 6 months, a significant reduction in systolic and diastolic blood pressure was seen in both the groups. The decrease in urinary protein creatinine ratio was significantly higher in cilnidipine group rather than amlodipine group. Thus, cilnidipine exerted greater antiproteinuric effect than amlodipine.Conclusions: Cilnidipine has antihypertensive effect equivalent to amlodipine but addition of cilnidipine rather than amlodipine to losartan decreased urine protein excretion in diabetic chronic kidney disease patients.

Hypertensive disorders of pregnancy occur in approximately 10% of pregnant women and preeclampsia in approximately 3% of pregnancies in the United States (1). The American College of Obstetricians and Gynecologists Task Force on Hypertension in Pregnancy defined chronic hypertension as a systolic blood pressure of 140 mmHg or more or a diastolic blood pressure of 90 mmHg or more on two separate occasions at least 2 h apart occurring before pregnancy or developing less than 20 weeks during pregnancy (2). Mild hypertension is a systolic blood pressure of 140 to 149 mmHg or a diastolic blood pressure of 90 to 99 mmHg (3). Moderate hypertension during pregnancy is a systolic blood pressure of 150 to 159 mmHg or a diastolic blood pressure of 100 to 109 mmHg (3). Severe hypertension during pregnancy is a systolic blood pressure of 160 mmHg or higher or a diastolic blood pressure of 110 mmHg or higher (3). Gestational hypertension occurs after 20 weeks during pregnancy (2). Preeclampsia is diagnosed if the woman has hypertension after 20 weeks of pregnancy with proteinuria greater than 300 mg in a 24-hour urine collection or a urinary protein/creatinine ratio ≥0.3 (2). Severe features of preeclampsia include thrombocytopenia, renal insufficiency, impaired liver function, pulmonary edema, and cerebral or visual symptoms (2). Modifiable risk factors for hypertensive disorders in pregnancy include increased body mass index, anemia, increased dietary sodium, and decreased dietary potassium intake (4,5).

Sir, Tacrolimus (Tac) is a T-cell-specific calcineurin inhibitor which prevents activation of helper T cells, thereby inhibiting transcription of the early activation genes of interleukin (IL)-2 and suppressing the production of tumor necrosis factor-α, IL-1β and IL-6 [1]. Thus, Tac is expected to have clinical benefits in patients with rheumatic diseases including systemic lupus erythematosus (SLE). Indeed, to date, several articles have described the efficacy of Tac in patients with difficult SLE [2, 3]. Recently, Tac combined with prednisolone (PDN) has been successfully administered without serious adverse effects, as induction and maintenance treatment for patients with proliferative and membranous lupus nephritis [2–6]. However, to our knowledge, the efficacy of Tac monotherapy in the treatment of patients with lupus nephritis has not been reported. We encountered a Japanese female patient with long-standing SLE, in whom relatively low-dose Tac monotherapy for disease flare was effective and safe. A 38-year-old Japanese female with a 24-year history of long-standing SLE with lupus nephritis suddenly developed significant proteinuria (∼1 g/day), arthralgia, hypocomplementemia and elevation of serum anti-dsDNA antibody titers. When she was 14 years old, active SLE with nephrotic-range proteinuria occurred. Percutaneous renal biopsy revealed Class IVb diffuse proliferative lupus nephritis. She was administered three courses of methyprednisolone pulse therapy followed by oral PDN combined with a 12-week course of cyclophosphamide (CPA) [7]. Thereafter, CPA was replaced by azathioprine, and the concomitantly administered PDN was tapered. The SLE activity, both clinical and serological, was under reasonably good control during maintenance therapy. The second renal biopsy, performed 12 months after the initial biopsy, revealed marked improvement to Class II lupus nephritis. After a 2-year treatment, PDN was successfully discontinued, and she remained free of SLE/lupus nephritis signs for the past 20 years or more. Although her blood pressure and renal function were normal at the time of the flare, significant proteinuria associated with hypocomplementemia and elevation of serum anti-dsDNA antibody titer developed 3 months prior to the time of presentation. However, the patient strongly refused to take PDN, mainly because of the cosmetic adverse effect. In this context, we decided to treat her with Tac monotherapy. After obtaining written informed consent, Tac was administered at a dose of 3 mg/day (0.06 mg/kg) once daily after the evening meal [4–6]. If the Tac-resistant flare persisted, PDN was scheduled to start for treating the flares. Response to the treatment is shown in Table 1. The outcome measures, such as the severity of proteinuria as estimated using the urinary protein/creatinine ratio (U-prot./cr.), the serum C3 level, the serum complement hemolytic activity (CH50), the serum titers of anti-dsDNA antibody (by enzyme-linked immunosorbent assay), the serum creatinine level and the SLE activity as assessed using the European Consensus Lupus Activity Measurement (ECLAM) index [8] were prospectively examined at baseline and after 1, 3, 6 and 12 months of treatment. At 1 month after the start of the protocol, a significant decrease in the ECLAM index was noted. After 3 months of treatment, the improvement in the ECLAM index was associated with a significant decrease in the U-prot./cre. ratio and marked recovery of hypocomplementemia. After 6 months of treatment, a tendency toward a marked decrease in the serum anti-dsDNA antibody titer was observed, with the serum creatinine level remaining unchanged. The blood levels of Tac in the patient were maintained at relatively low levels of

Objectives Diabetic kidney disease (DKD) is a frequent and serious complication in human diabetic patients, but data are limited in cats. This study was undertaken to assess whether diabetic cats are susceptible to DKD. Methods Kidney function was compared between 36 cats with diabetes mellitus (DM), 10 cats with chronic kidney disease (CKD) and 10 age-matched healthy cats by measuring routine kidney variables (serum creatinine [sCreat], serum urea [sUrea], urine specific gravity [USG], urinary protein:creatinine ratio [UPC]), urinary cystatin C:creatinine ratio and glomerular filtration rate (GFR). Urinary cystatin C (uCysC) was measured with a human particle-enhanced nephelometric immunoassay, validated to measure feline cystatin C, in all but two diabetic cats. GFR was evaluated by exo-iohexol clearance in 17 diabetic cats, all cats with CKD and all healthy cats. Results Diabetic cats had significantly (mean ± SD) lower sCreat (123 ± 38 vs 243 ± 80 µmol/l), sUrea (11 ± 3 vs 18 ± 7 mmol/l) and urinary cystatin C:creatinine ratio (6 ± 31 vs 173 ± 242 mg/mol), and a significantly higher USG (1.033 ± 0.012 vs 1.018 ± 0.006) and GFR (2.0 ± 0.7 vs 0.8 ± 0.3 ml/min/kg) compared with cats with CKD. Compared with healthy cats, diabetic cats only had significantly lower USG (1.033 ± 0.012 vs 1.046 ± 0.008). Proteinuria (UPC >0.4) was present in 39% of diabetic cats, in 30% of cats with CKD and in none of the healthy cats. However, the UPC did not differ statistically between the three groups. Conclusions and relevance Based on evaluation of routine kidney variables, GFR and uCysC as a tubular marker at a single time point, a major impact of feline DM on kidney function could not be demonstrated.

Immunoglobulin A vasculitis (IgA-V), formerly known as Henoch-Schönlein purpura (HSP), is the most common small vessel vasculitis in children. In recent years, the role of T cells in the pathogenesis of HSP/IgA-V has become a focus of research.Renal biopsy specimens from 22 pediatric patients diagnosed with Henoch-Schönlein nephritis (patient group) were compared to normal renal tissue in nephrectomy specimens from 20 pediatric patients diagnosed with Wilms tumor (control group). All renal specimens were scored according to International Study of Kidney Disease in Children (ISKDC) and Oxford classification. Immunohistochemical analyses of interferon-gamma (IFN-γ), interleukin (IL)-4, IL-17 and FOXP3 expression were performed.All glomeruli and tubules of the HSP/IgA-V patients showed significantly higher IFN-γ and IL-17 expression than those of the control group. Glomerular IFN-γ and IL-17 staining grades correlated with the urinary protein/creatinine ratio (r = 0.62, p = 0.02 and r = 0.507, p = 0.016, respectively). IL-17 expression also correlated with the percentage of crescents (r = 0.518, p = 0.014). IL-4 staining was present in only nine of the 22 patient biopsies and did not correlate with any of the parameters studied. Interstitial areas of patient biopsies had more FOXP3+ cells/μm(2) than those of the control group (p 0.001), but differences in glomerular and tubular FOXP3+ levels (cells/μm(2)) between the two groups were not statistically different. The ISKDC and Oxford scores did not correlate with any parameter studied. However, endocapillary hypercellularity did correlate with IFN-γ expression.Based on these results, we conclude that IFN-γ and IL-17 contribute to HSP/IgA-V in children.

Background.Progressive proteinuria indicates worsening of the condition in hypertensive disorders of pregnancy and hence its quantification guides clinician in decision making and treatment planning.Objective.To evaluate the efficacy of spot dipstick analysis and urinary protein-creatinine ratio (UPCR) in hypertensive disease of pregnancy for predicting 24-hour proteinuria.Subjects and Methods.A total of 102 patients qualifying inclusion criteria were evaluated with preadmission urine dipstick test and UPCR performed on spot voided sample. After admission, the entire 24-hour urine sample was collected and analysed for daily protein excretion. Dipstick estimation and UPCR were compared to the 24-hour results.Results.Seventy-eight patients (76.5%) had significant proteinuria of more than 300 mg/24 h. Dipstick method showed 59% sensitivity and 67% specificity for prediction of significant proteinuria. Area under curve for UPCR was 0.89 (95% CI: 0.83 to 0.95,P<0.001) showing 82% sensitivity and 12.5% false positive rate for cutoff value of 0.45. Higher cutoff values (1.46 and 1.83) predicted heavy proteinuria (2 g and 3 g/24 h, resp.).Conclusion.This study suggests that random urinary protein : creatine ratio is a reliable investigation compared to dipstick method to assess proteinuria in hypertensive pregnant women. However, clinical laboratories should standardize the reference values for their setup.

BACKGROUND The clinical significance of proteinuria has not been fully understood among patients who are affected with non-Hodgkin lymphoma (NHL). METHODS A 1-year prospective cohort study was conducted to ascertain the association between proteinuria and mortality in 46 hospitalized NHL patients. Proteinuria was defined as persistent dipstick test >= 1+, and the urinary protein creatinine ratio (UPCR),as a quantitative index of protein excretion, was measured simultaneously. A multivariable linear regression model was constructed to determine factors associated with UPCR. Statistical associations between proteinuria and time to mortality were analyzed using the Kaplan-Meier method and multivariable proportional hazards regression analysis, adjusted for covariates including disease severity, renal function, and serum interleukin-6(IL-6) concentration. RESULTS The prevalence of proteinuria was 15.2% in the NHL patients. UPCR was significantly associated with the serum IL-6 level (standardized beta = 0.360, p = 0.0440). The cumulative mortality was significantly higher in proteinuric patients than in non-proteinuric patients, with a graded relationship between the severity of UPCR and mortality. The mortality risk increased with increasing UPCR grade: the hazard ratio (95% confidence interval) was 4.90 (1.29 - 32.3) for UPCR 30 - 300 mg/gand 17.8 (2.84 - 150) for UPCR > 300 mg/g, respectively, when UPCR < 30 mg/g was set as the reference. CONCLUSIONS Proteinuria is a simple sign of coexisting systemic inflammation due to NHL and a harbinger of a poor prognosis.

Proteinuria is an established risk factor for progression of renal disease, including diabetic nephropathy. The predictive power of proteinuria, especially nephrotic range proteinuria, for progressive renal deterioration has been well demonstrated in diabetic patients with normal to relatively preserved renal function. However, little is known about the relationship between severity of proteinuria and renal outcome in pre-dialysis diabetic patients with severely impaired renal function.125 incident dialysis patients with type 2 diabetes were identified. This study was aimed at retrospectively evaluating the impact of nephrotic range proteinuria (urinary protein-creatinine ratio above 3.5 g/gCr) on renal function decline during the 3 months just prior to dialysis initiation.In total, 103 patients (82.4 %) had nephrotic range proteinuria. The median rate of decline in estimated glomerular filtration rate (eGFR) in this study population was 0.98 (interquartile range 0.51-1.46) ml/min/1.73 m(2) per month. Compared to patients without nephrotic range proteinuria, patients with nephrotic range proteinuria showed significantly faster renal function decline (0.46 [0.24-1.25] versus 1.07 [0.64-1.54] ml/min/1.73 m(2) per month; p = 0.007). After adjusting for gender, age, systolic blood pressure, serum albumin, calcium-phosphorus product, hemoglobin A1c, and use of an angiotensin-converting enzyme inhibitor or an angiotensin II receptor blocker, patients with nephrotic range proteinuria showed a 3.89-fold (95 % CI 1.08-14.5) increased risk for rapid renal function decline defined as a decline in eGFR ≥0.5 ml/min/1.73 m(2) per month.Nephrotic range proteinuria is the predominant renal risk factor in type 2 diabetic patients with severely impaired renal function receiving pre-dialysis care.

Chronic renal allograft injury is reflected by interstitial fibrosis and tubular atrophy (IF/TA) and by the accumulation of extracellular matrix (ECM). Metalloproteinases (MMPs) are renal physiologic regulators of ECM degradation. Changes in MMPs expression or activity may disturb ECM turnover leading to glomerular scarring and worsening renal function. Our goal was to investigate intragraft MMP2 and MMP9 activities and their correlation with renal dysfunction. Plasma MMP2 and MMP9 activities were analyzed as noninvasive markers of renal allograft deterioration. Transplanted patients were biopsied and histopathologically characterized as IF/TA+ or IF/TA-. Renal function was evaluated by serum creatinine, glomerular filtration rate (GFR) estimated by Modification of Diet in Renal Disease equation and urinary protein/creatinine ratio. Kidney and plasma MMP2 and MMP9 activities were analyzed by zymography. A significant renal dysfunction was observed in IF/TA+ patients. Intragraft proMMP9 showed a significant higher activity in IF/TA+ than in IF/TA- samples and was inversely correlated with the GFR. Intragraft proMMP2 activity tended to increase in IF/TA+ samples, although no statistic significance was reached. Circulating proMMP2 and proMMP9 activities did not show significant differences between groups. Our data provide evidence that correlates intragraft proMMP9 activity with the fibrotic changes and renal dysfunction observed in IF/TA. Fil: Racca, María Agustina. Universidad Nacional de Córdoba. Facultad de Medicina. Hospital Córdoba; Argentina Fil: Novoa, Pablo Antonio. Universidad Nacional de Córdoba. Facultad de Medicina. Hospital Córdoba; Argentina Fil: Rodríguez, Iván. Universidad Nacional de Córdoba. Facultad de Medicina. Hospital Córdoba; Argentina Fil: Della Vedova, Ana Belen. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Córdoba. Centro de Investigaciones en Bioquímica Clínica e Inmunología; Argentina Fil: Pellizas, Claudia Gabriela. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Córdoba. Centro de Investigaciones en Bioquímica Clínica e Inmunología; Argentina Fil: Demarchi, Marcela. Universidad Nacional de Córdoba. Facultad de Medicina. Hospital Córdoba; Argentina Fil: Donadio, Ana Carolina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Córdoba. Centro de Investigaciones en Bioquímica Clínica e Inmunología; Argentina

Chronic kidney disease (CKD) is common in cats, but the routine renal markers, serum creatinine (sCr) and urea, are not sensitive or specific enough to detect early CKD. Serum cystatin C (sCysC) has advantages over sCr, both in humans and dogs, and sCysC concentration is significantly higher in cats with CKD than in healthy cats. The objective of this study was to determine the effect of age, sex and breed on feline sCysC and to establish a reference interval for feline sCysC. In total, 130 healthy cats aged 1-16 years were included. sCysC was determined using a validated particle-enhanced nephelometric immunoassay. sCr, urea, urine specific gravity, urinary protein:creatinine ratio (UPC) and systolic blood pressure (SBP) were also measured. No significant differences in sCysC concentration were observed among young, middle-aged and geriatric cats, female intact, female neutered cats, male intact and male neutered cats, or among purebred and domestic short-or longhaired cats. The 95% reference interval for feline sCysC was determined to be 0.58-1.95 mg/L. sCr was significantly higher in geriatric cats than young cats. Serum urea in geriatric cats was significantly higher than in middle-aged and young cats (P = 0.004 and P 0.001, respectively). SBP in geriatric cats was significantly higher than in both middle-aged and young cats (P = 0.004 and P = 0.040, respectively). Male neutered and female neutered cats had significantly higher serum urea concentrations than female intact cats (P = 0.003 and P = 0.006, respectively). Male intact cats had a significantly higher UPC than female intact and female neutered cats (P = 0.02 for each comparison). There were no significant differences among sex groups for USG. It is of concern that sCysC in the majority of cats with CKD in previous studies falls within the reference interval calculated in this study. Further studies are warranted to evaluate the diagnostic value of sCysC as a renal marker in cats.

Background. Hepatitis B virus (HBV)-associated membraConclusion. These results suggest that the family members nous nephropathy (HBVMN) is an important cause of childand household contacts of children with HBVMN are at very hood nephrotic syndrome in regions endemic for the virus, but high risk of HBV carriage; they also have asymptomatic prolittle is understood of the biosocial context in which the disease teinuria at a significantly higher rate than community-based develops. We evaluated HBV status and proteinuria in family controls. The HBV carrier status was not associated with promembers and household contacts of index children with teinuria, a finding supported by peak prevalences of proteinuria HBVMN to test the hypothesis that HBV carriage and asympin those under five years but no corresponding peak for HBV tomatic proteinuria are closely linked and may be causally associated. carriage. Proteinuria may indicate glomerular basement memMethods. Thirty-one black children with biopsy-proven brane dysfunction. Environmental and social factors may unHBVMN were the index cases. One hundred and fifty-two derpin development of these two covert disorders, but are family members and 43 black household contacts were the insufficient to account for the index cases of HBVMN. The subjects of the study. We assessed HBV carrier status by testing emergence of children with HBVMN from such households for HBV antigens and antibodies using enzyme-linked immu- additionally depends on unidentified and possibly genetic facnosorbent assays (ELISA) and for HBV DNA by using slot- tors. blot hybridization and the polymerase chain reaction. Sequencing of the precore region of HBV was done in a subset of both index cases and subjects. Proteinuria was assessed by measuring The available information indicates that genetic, sothe urinary protein/creatinine ratio. cial, economic, infectious, nutritional, and climatic facResults. Seventy-two (37%) of the 195 family members and household contacts were HBV carriers, and 53 (27%) had a tors make differing contributions to pediatric renal disorprotein/creatinine ratio greater than the physiological limit. ders [1]. Genetic causes may predominate in indusThe frequency of abnormal proteinuria was not significantly trialized countries, whereas exposure to pathogens may different in those with [22 out of 72 (30.5%)] or without [33 out be more important in the third world [1, 2]. In order to of 104 (32%)] HBV carriage. This lack of association remained explore this subject further, we chose to study the settings when carriers were classified into those who were HBsAg positive only and those with active viral replication (HBsAg and/ in which the hepatitis B virus (HBV)-associated memor HBeAg and/or HBV DNA; P 5 0.01). Family members branous nephropathy (HBVMN) emerges. were more predisposed to HBV carriage than household con- Epidemiological, clinical, and immunological evidence tacts, but abnormal proteinuria was present with equal fre- suggests a causal association between HBV carriage and quency (P 5 0.48). Age had a significant impact on proteinuria, the development of HBVMN [2, 3], although some inveswith children less than five years being more likely to have abnormal proteinuria (P 5 0.008). The prevalence of abnormal tigators dispute this interpretation [3]. The pathogenetic proteinuria in family members and household contacts of the mechanisms by which individuals with chronic HBV inindex cases was more than that in community-based controls. fection develop MN remain enigmatic, although a number of immunologic processes related to immune complex deposition have been implicated [4, 5]. Genetic

Transgenic mice (T26) bearing the envelope, regulatory, and accessory genes of HIV- I develop renal disease resembling human HIV-associated nephropathy (HIVAN). Effects of vehicle (VEH) and the angiotensin-converting enzyme inhibitor captopril (CAP) were examined in wild-type (WT) or T26 mice treated from 7 to 100 d of age. Mortality was lower in CAP T26 mice (30 mg/kg: 8%; 100 mg/kg: 12%) than VEH T26 mice (52%). The urinary protein/creatinine ratio was increased in VEH T26 mice (19.5+/-7.60) versus WT mice (6.1+/-0.83), but not in low-dose (7.3+/-0.94) or high-dose (8.2+/-1.02) CAP T26 mice. Blood urea nitrogen was higher in VEH T26 mice (52+/-16.2 mg/dl) than VEH WT mice (24+/-0.8). Blood urea nitrogen was also elevated in CAP WT (high dose: 43+/-2.1 mg/dl) and T26 mice (high dose: 42+/-2.4 mg/dl). Glomerular injury was higher in VEH T26 mice (6.8+/-0.58) than VEH WT mice (0.2+/-0.08) or CAP T26 mice (low dose: 1.1+/-0.17; high dose: 0.7+/-0.13). Tubulointerstitial injury was also greater in VEH T26 mice (1.1+/-0.10) than VEH WT mice (0.2+/-0.08) or CAP T26 mice (low dose: 0.4+/-0.10; high dose: 0.3+/-0.10). These data validate recent nonrandomized studies of captopril in HIV-infected patients, and suggest that an angiotensin-converting enzyme substrate is an important mediator in HIVAN. A randomized placebo-controlled trial of captopril in HIVAN may be warranted.

Membranoproliferative glomerulonephritis (MPGN) is a distinctive form of chronic glomerulonephritis. We present the results of our 96 paediatric patients with MPGN, reporting the survival and factors affecting prognosis in these patients. There were 64 boys and 32 girls with an age range of 2-17 (mean 10.6 +/- 3.7) years. All patients initially received oral corticosteroid therapy; remission was achieved in 22.9%. The unresponsive 77.1% either received cyclophosphamide and/or pulse methylprednisolone; 25.4% and 50.0% of these patients entered complete remission, respectively. The overall 1-year renal survivals of the MPGN patients were 90.1%, 5-year and 10-year survival rates were 81.9% and 61%, respectively. At multivariate analysis the factors affecting renal prognosis were haematuria at presentation (p0.05, risk factor 3.52), urinary protein/creatinine ratio (p0.05, risk factor 1.06 per 1 unit) and low haemoglobin values (p0.05, risk factor 1.43 for each 1 g/dl decrement). We suggest that more aggressive immunosuppression therapy should be instituted in patients unresponsive to steroids and that the aforementioned risk factors are higher for the development of renal failure.

The number and distribution of glomerular anionic sites using polyethyleneimine (PEI) and the ultrastructural changes in the adjacent glomerular basement membrane (GBM) of 33 children with nephrotic syndrome were studied. Compared to the number of PEI-labelled anionic sites in the lamina rara externa per 1000 nm length of the GBM in eight controls (mean +/- SD, 25.0 +/- 1.49); there was a significant decrease in four patients with minimal change nephrotic syndrome (MCNS; 15.25 +/- 2.98, P < 0.05); 10 patients with focal glomerulosclerosis (16.0 +/- 5.1, P < 0.014); 14 patients with membranous nephropathy (14.1 +/- 3.83, P < 0.009), and five patients with membranoproliferative glomerulonephritis (20.04 +/- 1.69, P < 0.036). A moderate inverse correlation between anionic site numbers and proteineuria (estimated by urinary protein creatinine ratio) was found in MCNS only (r = -0.6). These findings suggest that a reduction in the glomerular anionic sites may be only partly responsible for proteineuria in the different types of childhood nephrosis, except for minimal change nephrotic syndrome, where it probably plays a major role.

BACKGROUND Proteinuria is a major predictor for progression of renal disease, including diabetic nephropathy. In a post hoc analysis of the ORIENT, a double-blinded randomized trial of 566 type 2 diabetic patients with nephropathy, we examined the risk association of composite renal outcome [end-stage renal disease, ESRD, doubling of serum creatinine (SCr) and death] with baseline, change and residual urinary protein/creatinine ratio (UPCR). METHODS We estimated the hazard ratios (HRs) with 95% confidence interval (CI) of composite renal outcome with baseline UPCR (low

Background Comprehensive care in homozygous sickle cell disease (HbSS) entails universal neonatal screening and subsequent monitoring of identified patients, a process which has been streamlined in the neighbouring island of Jamaica. In preparation for a similar undertaking in Barbados, we have developed a database of persons with known HbSS, and have piloted processes for documenting clinical manifestations. We now present a brief clinical profile of these findings with comparisons to the Jamaican cohort. Methods HbSS participants were recruited from clinics and support groups. A history of select clinical symptoms was taken and blood and urine samples and echocardiograms were analysed. A re-analysis of data from a previous birth cohort was completed. Results Forty-eight persons participated (32 F/16 M); age range 10–62 yrs. 94% had a history of ever having a painful crisis. In the past year, 44% of participants had at least one crisis. There were >69 crises in 21 individuals; 61% were self-managed at home and the majority of the others were treated and discharged from hospital; few were admitted. The prevalence of chronic leg ulceration was 27%. Forty-two persons had urinalysis, 44% were diagnosed with albuminuria (urinary protein/creatinine ratio ≥30 mg/g). Thirty-two participants had echocardiography, 28% had a TRJV ≥ 2.5 m/s. Re-analysis of the incidence study revealed a sickle gene frequency (95% CI) of 2.01% (0.24 to 7.21). Conclusion Although we share a common ancestry, it is thought that HbSS is less common and less severe in Barbados compared to Jamaica. The Jamaican studies reported a sickle gene frequency of 3.15 (2.81 to 3.52); the prevalence of chronic leg ulcers and albuminuria was 29.5% and 42.5% respectively. These comparisons suggest that our initial thoughts may be speculative and that HbSS may be an underestimated clinical problem in Barbados. A prospective neonatal screening programme combined with centralized, routine monitoring of HbSS morbidity and outcomes will definitively answer this question and will improve the evidence-based care and management of HbSS in Barbados.

Tyrosinaemia type 1 (HT1) is a rare disorder of tyrosine metabolism leading to liver failure and hepatocellular carcinoma. Treatment previously consisted of dietary restriction and orthotopic liver transplantation (OLT) but was transformed by the introduction of nitisinone in 1992. We describe the impact of nitisinone on the outcome and need for OLT in a single centre.A retrospective analysis was performed of patients treated for HT1 at Birmingham Children's Hospital from 1989-2009.Thirty eight patients were treated during the study period. Prior to 1992 6/7 (85.7 %) underwent OLT compared to 7/31 (22.6 %) after 1992 (p = 0.004) when nitisinone treatment was available. Furthermore, nitisinone-treated patients proceeding to OLT started treatment at a median age of 428 (86-821) days compared to 52 (2-990) days in those who did not (p = 0.004). Pre-OLT calculated glomerular filtration rate (cGFR) was similar in both groups but nitisinone prevented early decline after OLT (pre-nitisinone median 99.8 to 45.8 ml/min/1.73 m2, p = 0.02 versus nitisinone-treated group median 104.3 to 89.9 ml/min/1.73 m2, p = 0.5). Urinary protein:creatinine ratio (PCR) fell post-OLT to within the normal range for those treated with nitisinone but remained elevated in those not treated with nitisinone. Tubular reabsorption of phosphate (TRP) was normal or near normal in both groups pre-OLT and post-OLT. Hypertension was commoner and more severe in those not treated with nitisinone.Nitisinone reduces the need for OLT particularly when started early. For those progressing to OLT the use of prior nitisinone therapy results in a preservation of their subsequent renal function.

The hereditary nephritides are often progressive, resulting in kidney failure and the need for renal replacement therapy. There is no currently known beneficial treatment for these disorders. We observed three patients with hereditary glomerulonephritis with plasma creatinine concentrations ranging from 1.7 to 2.0 mg/dL who were treated with angiotensin-converting enzyme inhibitors (ACEIs) for 3.5 to 6 years. Angiotensin-converting enzyme inhibitor therapy was accompanied by a decrease in the mean arterial pressure (MAP) from 115 +/- 10 mm Hg to 93 +/- 2 mm Hg (+/- SD), a decrease in the mean urinary protein/creatinine ratio from 2,910 +/- 1,720 mg/g to 391 +/- 355 mg/g, and stabilization of the decline of creatinine clearance with time in two of the three patients. Based on this apparent benefit of ACEIs in hereditary nephritis, we suggest that a prospective controlled trial of ACEIs should be undertaken among a large group of such patients. Pending the results of such a study, ACEIs should be considered for the treatment of patients with proteinuric and progressive hereditary nephritis.

Healthy dogs usually excrete small amounts of protein in urine. Persistently high proteinuria is usually a marker of kidney disease. The urinary protein: creatinine ratio (UPC) is used in quantifying urine protein excretio ney diseases, guiding recommendations for monitoring and treatment of kidney diseases and evaluation of prognosis. However, use of UPC ratio has not been well established/ used to diagnose renal diseases in dogs in Sri Lanka. Therefore, for the first time in Sri Lanka, we used this method to detect UPC ratio of healthy dogs (n=51). Once we established the UPC ratios of healthy dogs, UPC ratios were measured in working dogs (n=45) in Kennels Division of Sri Lanka Police, since renal diseases are a common cause of mortality in these dogs. In control group, the mean UPC ratio was 0.06±0.05. This was similar to the UPC ratio of tracking group among working dogs. Two out of 22 dogs used for explosive duties had UPC ratio within the borderline proteinuric stage (0.2-0.5) according to the staging system implemented by the International Renal Interest Society (IRIS). In the narcotic group 2 out of 12 dogs were borderline proteinuric and one dog was proteinuric. In this study, we have successfully established the measurement of UPC ratio to detect proteinuria in Sri Lankan dogs and have identified dogs that are susceptible to renal diseases.

Background: Patients (pts) with transfusion-dependent anemias now have longer life expectancy due to improved quality of care, in particular iron chelation therapy (ICT). Longer life and drug exposure increase the chance of complications, such as changes in renal function, which may be age-, disease- or drug-related. In light of lifelong transfusions and dependence on ICT, it is relevant to understand the long-term ICT safety profile. Published data show some pts receiving ICT experience changes in markers of renal function, mostly within normal limits, non-progressive and reversible with dose reduction and/or interruption, although follow-up was limited to ≤5 years. This retrospective study assessed long-term renal safety of deferasirox in Italian pts with transfusional hemosiderosis who participated in the deferasirox registration studies and continued treatment for up to 10 or more yrs. Methods: Italian pts with β thalassemia, sickle cell disease, MDS or other anemias who participated in deferasirox registration studies and extensions (studies 105, 106, 107, 108 or 109), received ≥1 dose of deferasirox, had ≥1 post-baseline (BL) serum creatinine (SCr) measurement, and had medical records available could be included. BL and worst values were recorded during the prospective studies; values were collected retrospectively in 3-month periods from registration trial end until the latest pt assessment for SCr, urinary protein/creatinine ratio (UPCR) and creatinine clearance (CrCl, if available). Primary endpoint was SCr trend over time. Secondary endpoints included notable renal function values (SCr >33% increase from BL and >ULN at two consecutive measurements ≥7 days apart; CrCl Results: Of the 366 Italian pts in the registration studies, 282 pts received ≥1 dose of deferasirox in registration studies and were included (Table). In the registration studies (n=282), mean (SD) duration of deferasirox exposure was 3.5 (1.6) yrs and mean daily deferasirox dose was 1032.2 (438.8) mg. In the retrospective period (n=215), mean (SD) duration of deferasirox exposure was 6.1 (2.8) yrs and mean daily deferasirox dose was 1385.6 (500.0) mg. 63.5% of pts received other ICT during the retrospective period either as combination therapy or alone (Table). In the overall population, mean SCr and UPCR values were within normal limits and stable over time during the retrospective period (Figure). In the registration studies, notable SCr values were observed in 12 (4.3%) pts, notable UPCR values in 16 (5.7%) pts and notable CrCl values in 17 (6.0%) pts (CrCl values missing n=91). In the retrospective period, notable SCr values were observed in 15 (5.3%) pts, notable UPCR values in 17 (6.0%) pts (UPCR values missing n=99) and notable CrCl values in 14 (5.0%) pts (missing n=207). In the retrospective period, regardless of ICT received, renal AEs were reported in 86 (30.5%) pts, severe renal AEs in 7 (2.5%) pts. 54% of pts with a renal AE took one concomitant medication associated with potential nephrotoxicity. The most common renal AEs were nephrolithiasis (n=31, 11.0%), renal colic (n=28, 9.9%), increased/abnormal UPCR (n=16, 5.7%), increased blood creatinine (n=12, 4.3%) and proteinuria (n=13, 4.6%). 8 pts (2.8%) had 10 serious renal AEs: nephrolithiasis, renal colic (n=2 each), increased blood creatinine, acute kidney injury, hematuria, hydronephrosis, renal failure, urethral stenosis (n=1 each); at the time of serious AE pts were receiving deferasirox (n=4), deferoxamine or deferiprone (n=3) or no ICT (n=1). Of 86 pts who had renal AEs, 33 (11.7%) were suspected to be deferasirox-related, most commonly increased UPCR (n=14, 5.0%), proteinuria (n=11, 3.9%) and increased blood creatinine (n=8, 2.8%). 5 (1.8%) pts discontinued because of renal AEs: increased blood creatinine, glycosuria (n=2 each), proteinuria (n=1). Conclusions: This is the longest follow-up analysis in pts with transfusion-dependent anemias available today and indicates stable renal function and a lack of any progressive worsening of renal function during long-term deferasirox treatment (3.5 yrs registration studies; 6.1 yrs retrospective period). Results support a favorable long-term risk:benefit renal safety profile for deferasirox in the treatment of transfusional iron overload. Disclosures Origa: Novartis: Honoraria; Apopharma: Honoraria. Piga:Apopharma: Honoraria; Novartis: Research Funding. El-Ali:Novartis: Employment. Han:Novartis: Employment. Castiglioni:Novartis: Employment. Forni:Novartis, Celgene: Research Funding.

Background Nucleosomes are basic elements of chromatin and are considered to be the major antigens in the pathophysiology of systemic lupus erythematosus (SLE). Objectives This study aimed to look for associations between anti nucleosome antibodies and clinical and laboratory parameters in SLE Methods This retrospective study was done in department of Clinical immunology & Rheumatology in Christian Medical College, Vellore, India. Patients with SLE by SLICC 2012 criteria between March 2013 and September 2015 subjected to anti nucleosome antibody test formed the study cohort. A cut off of ≥20 U/ml by ELISA was defined as per manufacturer9s (Euroimmune, Germany) instructions. Associations of anti nucleosome antibody with clinical and laboratory parameters in SLE was studied. Results Anti nucleosome antibody was available for 238 patients with SLE. Mean age of the patients was 28.98±9.01 years with male to female ratio of 17: 221. Median disease duration was 8 (5–12) months prior to doing this test. Positive titers of anti nucleosome antibody (≥20 U/ml) were noted in 107 patients (46.5%). Renal involvement was seen in 134 (56.3%) patients. Univariate analysis reflected raised anti-c1q antibody, ESR, urinary protein creatinine ratio (UPC), anti dsDNA antibody, SLE disease activity index (SLEDAI), renal SLEDAI, low C3 and C4 as significant association of elevated anti nucleosome antibody levels. No significant association with arthritis, serositis, major infections, serositis, anti-phospholipid antibodies, autoimmune hematological cutaneous, neuropsychiatric, cardiovascular, respiratory, vasculitic and gastrointestinal manifestation was present. Multivariate regression analysis showed that raised anti-c1q antibodies and DsDna were associated with raised anti nucleosome antibody with odds ratio of 17.46 (95 CI: 1.46–213.86, p=0.02) and 82.94 (95 CI: 3.62–189.93, p=0.006) respectively. Conclusions As per literature search, this is the largest single centre study of anti nucleosome antibody in SLE. In this study, raised anti-c1q antibodies and DsDna were independently associated with raised anti nucleosome antibody in SLE. Disclosure of Interest None declared

Background/introduction Quarterly monitoring of creatinine is likely to be recommended by WHO for those on PrEP, even though there were no significant differences in creatinine in placebo-controlled trials. Establishing the appropriate level of monitoring of PrEP is important. Methods PROUD is an open-label, randomised trial of Truvada as PrEP in MSM. HIV serology and serum creatinine was done at PrEP baseline (‘start’). Clinics were advised to collect creatinine or urinary protein-creatinine ratio (UPCR) if there was ≥1+ protein on urinalysis at the month 1 visit (m1). Here’we present the renal monitoring results at “start” and m1 with eGFR (ml/min/1.73m 2 ) calculated by the CKD-EPI equation. Results 445 (93%) of 481 had baseline creatinine, 13 (3%) had UPCR, and 23 (5%) neither. The median eGFR was 106. Only one was 90 dropped 20%, one to 59. He stopped PrEP and did not attend thereafter. Of the 7, none had abnormal urinalysis; 4 had UPCR – all normal. 41 (79%) of 52 with eGFR 60–90 at baseline remained at this level, the remainder increased to >90. Discussion/conclusion The mean change in eGFR at month 1 is not clinically significant. Excepting one individual who could not be further evaluated, there were no clinically meaningful changes at m1. Further work will explore the relationships between eGFR and proteinuria.

The aim of this research was to compare the accuracy of urinary protein/creatinine ratio (PCR) and albumin/creatinine ratio (ACR) in defining optimal cut-off points to rule-out significant proteinuria (>300 mg/24 h) in pregnancy. The secondary outcome measure was to determine the investigation of choice to evaluate proteinuria used by maternity units in the UK. PCR and ACR were calculated on first (PCR1, ACR1) void urine samples of the 24-hour urinary protein collection (24UP). Sensitivity and specificity was calculated for different cut-off points for PCR1 and ACR1 to rule-out significant proteinuria. An online survey was sent to RCOG members questioning them on their investigation of choice to evaluate proteinuria. We concluded from our results that both PCR and ACR are good rule-out tests for significant proteinuria in pregnancy using cut-off points of

Diabetes mellitus is the commonest cause of ESRD worldwide and third most common cause in Nigeria. Recent reports from Nigeria indicate the prevalence of diabetic nephropathy as an aetiology of ESRD is increasing necessitating early diagnosis of diabetic nephropathy. We measured the urinary excretion of N-acetyl-beta-D-glucosaminidase (NAG), NAG/creatinine ratio, urinary protein-creatinine ratio and calculated eGFR in 30 recently diagnosed nonhypertensive diabetics and 67 controls. The age and sex distribution, systolic blood pressure, serum and urinary creatinine were similar for both groups. There was higher urinary excretion of NAG (304 versus 184 μmol/h/L,P<0.001) and NAG/creatinine ratio (21.2 versus 15.7 μmol/h/L/mmolCr,P<0.001) in the diabetics than controls. There was a strong correlation between NAG/creatinine ratio and albumin/creatinine ratio (r=0.74,P<0.001). A multivariate linear regression model showed a significant linear relationship between NAG/creatinine ratio and albumin/creatinine ratio after adjusting for the effect of blood pressure, age, sex, and serum creatinine. The strong association found between albumin/creatinine ratio and NAG/creatinine ratio perhaps indicates the need for further investigation of the clinical utility of NAG/creatinine ratio as a screening tool for early nephropathy in African diabetics.