Higher Urinary Protein Excretion Research Articles

Accelerated involution of germinal center in palatine tonsils in IgA nephropathy.

Altered immunological responses in the palatine tonsils may be involved in the pathogenesis of IgA nephropathy (IgAN). The germinal center serves as the site for antigen-specific humoral immune responses in the palatine tonsils. Germinal center involution is frequently observed in the palatine tonsils of IgAN (IgAN tonsils). However, the pathogenic significance of these characteristic changes remains unclear. This study aimed to investigate the morphological changes in secondary lymphoid follicles in IgAN tonsils and to evaluate the correlation between the morphometric results and the clinicopathological severity of IgAN. The tonsils of age-matched patients with recurrent tonsillitis (RT tonsils) were used as controls. The correlation between the degree of lymphoid follicular involution and histopathological severities in clinical or kidney biopsy was evaluated. In total, 87 patients with IgAN were included (48% male, median age 35 years, median estimated glomerular filtration rate: 74 mL/min/1.73 m2). Compared to RT tonsils, IgAN tonsils showed smaller median sizes of lymphoid follicles and germinal centers (P < 0.001). The relative areas of lymphoid follicles (%LFA) and germinal centers (%GCA) in the total tonsillar tissue were smaller in the IgAN tonsils than in the RT tonsils (P < 0.001). In contrast, the median proportion of mantle zones in the total tonsillar tissue was comparable between the groups. A lower %LFA was associated with a longer period from the onset of urinary abnormalities to biopsy diagnosis and higher urinary protein excretion (P = 0.01). %LFA showed significant negative correlations with frequencies of glomeruli with both global and segmental sclerosis. The present study confirmed accelerated germinal center involution in the tonsils of patients with IgAN. This characteristic change in the IgAN tonsil correlates with heavy proteinuria and advanced chronic histopathological changes in the kidneys, thereby suggesting the involvement of repeated tonsillar immunoreactions during IgAN progression.

Long‐term prognosis of focal segmental glomerulosclerosis treated with therapeutic low‐density lipoprotein‐apheresis in patients with severe kidney dysfunction and proteinuria

AbstractBackgroundThe prognosis of focal segmental glomerulosclerosis patients with nephrotic syndrome is estimated to be 10%–20% in 5 years and 30%–50% in 10 years, leading to end‐stage kidney disease. The response rate with steroid therapy is 40%–60%. Therapeutic low‐density lipoprotein‐apheresis (LDL‐A) may be effective in patients with steroid resistance. Information regarding the long‐term prognosis of patients with focal segmental glomerulosclerosis receiving this therapy is scarce.MethodsWe investigated the effectiveness of treatment in 50 patients with primary focal segmental glomerulosclerosis diagnosed between 1961 and 2017 at Kanazawa University Hospital and related facilities. The patients were observed at least 12 months after biopsy or until end‐stage kidney disease occurrence or death.ResultsLDL‐A was performed in four patients who presented with steroid‐resistant nephrotic syndrome (two patients had concurrent acute renal failure for which hemodialysis was performed). In comparison with 17 patients who did not receive LDL‐A after 1989, the LDL‐A group had higher urinary protein excretion (13.7 vs. 5.2 g/day, P = 0.053) and serum creatinine (4.11 vs. 1.65 mg/dL) levels at onset, and a numerically higher remission rate (75.0% vs. 58.7%) compared with the nonlipoprotein‐apheresis group.ConclusionTherapeutic LDL‐A can be performed for critical cases and may improve the remission rate.

Mediterranean Style Diet and Kidney Function Loss in Kidney Transplant Recipients.

Despite improvement of short-term graft survival over recent years, long-term graft survival after kidney transplantation has not improved. Studies in the general population suggest the Mediterranean diet benefits kidney function preservation. We investigated whether adherence to the Mediterranean diet is associated with kidney outcomes in kidney transplant recipients. We included 632 adult kidney transplant recipients with a functioning graft for ≥1 year. Dietary intake was inquired using a 177-item validated food frequency questionnaire. Adherence to the Mediterranean diet was assessed using a nine-point Mediterranean Diet Score. Primary end point of the study was graft failure and secondary end points included kidney function decline (doubling of serum creatinine or graft failure) and graft loss (graft failure or death with a functioning graft). Cox regression analyses were used to prospectively study the associations of the Mediterranean Diet Score with study end points. During median follow-up of 5.4 (interquartile range, 4.9-6.0) years, 76 participants developed graft failure, 119 developed kidney function decline, and 181 developed graft loss. The Mediterranean Diet Score was inversely associated with all study end points (graft failure: hazard ratio [HR], 0.68; 95% confidence interval [95% CI], 0.50 to 0.91; kidney function decline: HR, 0.68; 95% CI, 0.55 to 0.85; and graft loss: HR, 0.74; 95% CI, 0.63 to 0.88 per two-point increase in Mediterranean Diet Score) independent of potential confounders. We identified 24-hour urinary protein excretion and time since transplantation to be an effect modifier, with stronger inverse associations between the Mediterranean Diet Score and kidney outcomes observed in participants with higher urinary protein excretion and participants transplanted more recently. Adherence to the Mediterranean diet is associated with better kidney function outcomes in kidney transplant recipients.

A15395 Transgenic Rat Expressing the Human Chymase Gene as a Model of Human Hypertensive Disease

Objectives: An incorrect knowledge of the primary angiotensin (Ang) II-forming enzyme and substrate in human cardiovascular organs continues to impede development of therapies with higher efficacy in suppressing intracrine Ang II actions. To circumvent this limitation, an experimental model harboring the human chymase (hCHY) and angiotensinogen genes are required. Toward this goal we describe the first transgenic rat model with whole body expression of the hCHY gene (hCHY Tg(+)). Methods: Initial characterization of 17–20 week old hCHY Tg(+) transgenic animals of both sexes (males = 9; females = 14) on the level of chymase mRNA and protein expression in hearts and kidneys as well as phenotypic changes are documented here. Sex- and age-matched wild type (WT) littermates (male = 6; females = 6) served as controls. Results: The presence of hCHY mRNA and protein was confirmed in hearts and kidneys of male and female transgenic animals while mRNA and protein of the transgene were not detected in the organs of WT controls. When compared to sex-matched WT littermates, systolic blood pressure recorded by telemetry was higher during both day- and night-time in male but not in female hCHY Tg(+) rats (Figure). While echocardiographic analysis of the left ventricular wall thickness and function showed no differences between WT and hCHY Tg(+) transgenic animals of both sexes, higher urinary protein excretion was observed in male (7.7 ± 1.8 vs 3.5 ± 1.3 mg/mg creatinine, p < 0.05) but not female hCHY Tg(+) rats (0.5 ± 0.04 vs 1 ± 0.3 mg/mg creatinine). Conclusion: Our study suggests that the in vivo expression of hCHY in transgenic rats is associated with hypertension and increased vascular permeability as reflected by the rise in urinary protein excretion in males.

Acute kidney injury in children with nephrotic syndrome: a single-center study.

ABSTRACTBackgroundChildren with nephrotic syndrome (NS) are at risk for the development of acute kidney injury (AKI) through a variety of mechanisms.The frequency of NS hospitalizations complicated by AKI has almost doubled in the last decade. Children with AKI have longer hospital length of stay and increased need for intensive care unit admission. The main objectives of this study were to determine the incidence, clinical characteristics, risk factors and short-term outcome of AKI in children hospitalized with NS.MethodsIn this retrospective study, 355 children ≤18 years of age with a clinical diagnosis of NS admitted in the Department of Nephrology, Gauhati Medical College and Hospital from January 2012 to December 2015 were reviewed.ResultsThe incidence of AKI in children with NS was found to be 23.66%, 11.24%, 7.95% and 4.48% of children entered Pediatric Risk, Injury, Failure, Loss, End-Stage Renal Disease (pRIFLE) Stages R, I and F, respectively. Infection {odds ratio [OR] 2.53 [95% confidence interval (CI) 1.52–4.22]} and nephrotoxic medication exposure [OR 7.8 (95% CI 4.06–15.01)] were common factors associated with AKI. Children with steroid-dependent NS (SDNS) and steroid-resistant NS (SRNS) were more likely to develop AKI compared with children with steroid-sensitive NS (SSNS). The mean time to recovery for groups pRIFLE Stages R, I and F were 15 ± 2 , 22 ± 3 and 28 ± 5 days, respectively. Children with NS who were hypertensive, had higher urinary protein excretion and low serum albumin were more prone to develop AKI.ConclusionsAKI is not uncommon in children with NS. Infection and exposure to nephrotoxic drugs are common factors associated with AKI. AKI is more frequent in SDNS and SRNS compared with SSNS. The mean time to recovery is prolonged with more severe AKI.

Abstract P176: Maternal and Neonatal Outcomes in Normal and Preeclamptic Pregnancies - A Comparative Prospective Study

Background: Preeclampsia (PreE) is de novo development of hypertension and proteinuria after 20 weeks of gestation with multiple pathophysiologic triggers affecting 3-8% of pregnancies. PreE has a significant link to alterations of feto-placental stress that pass to the offspring causing detrimental effects. We assessed and compared the pregnancy outcomes between patients with and without PreE. Methods: We recruited 35 normal pregnant (NP) and 25 PreE consenting patients in an IRB approved prospective study at Scott &amp; White Memorial Hospital, Temple, Texas. We evaluated maternal age, body mass index (BMI), blood pressures, proteinuria, and gestational age at delivery. We divided the PreE subjects into early (before 34 weeks) and late PreE (after 34 weeks) groups and compared their outcomes. Placental thickness and volumes were measured. We also evaluated neonates for intrauterine growth restriction (IUGR), gestational age at birth, anthropometric measurements including Ponderal Index (PI), length of hospitalization and other neonatal complications. Comparisons were performed using Student’s t test. Results: Maternal: The systolic blood pressure (SBP) and diastolic blood pressure (DBP) were higher in PreE (SBP 166 ± 11; DBP 93 ± 10) compared to normal pregnancies (SBP 122 ± 10; DBP 74 ± 9; p &lt;0.05 for each case). PreE mothers had higher urinary protein excretion (457mg/24h ± 140) compared to NP (160 mg/24h ± 44; p &lt;0.05 for each case). We did not find any difference in body mass index (BMI). Placenta: The placental thickness in early PreE subjects was 25mm compared to 32mm in late PreE (p &lt;0.05) and placental volume in early PreE 296 cm 3 compared to 393cm 3 (p &lt;0.05). Neonatal: The average GA at delivery was lower in PreE (34.8 wks. ± 4) compared to NP (39.2 weeks ± 0.3; p &lt;0.05). Average hospital stay for PreE babies were longer (20 days ± 5) compared to NP (2 days ± 1; p &lt;0.05). The PreE babies were SGA with lower PI (2.28 ± 0.3) compare to the NP babies (2.95 ± 0.2; p &lt;0.05). Gestational age at delivery in early PreE is 32.4 weeks vs 36.8 weeks in late PreE (p &lt;0.05). About 56% of the infants who are born to early PreE are small for gestational age (SGA) and 30% of the infants who are born to late PreE are SGA. PreE babies had multiple complications compared to NP babies.

Abstract P329: Age- and Sex-differences in Salt Sensitivity and Renal Function in a Rat Model of Autosomal Recessive Polycystic Kidney Disease

Background: Most forms of hypertension are influenced by gender and salt sensitivity, however, the interplay of these two factors and their functional consequences in polycystic kidney disease (PKD)-associated hypertension are poorly understood. Thus, we tested the hypothesis that age and male sex would pre-dispose animals with PKD to hypertension and risk of renal dysfunction. Methods: We used the Pkhd1 pck rat model of autosomal recessive PKD to study sex differences in blood pressure in response to a high salt diet (HSD). Two month- and eight month-old male and female Pkhd1 pck rats were surgically implanted with telemetry transmitters and allowed to recover for at least one week before obtaining baseline mean arterial pressure (MAP). Rats were maintained on either HSD (4% NaCl) or normal rat chow (0.49% NaCl) for 3 weeks. At the end of the study, rats were placed in metabolic cages and a 24 hr urine sample was collected before measuring GFR (transdermal sinistrin clearance). Results: In the 2-month old Pkhd1 pck rats, blood pressures were in a normal range and there were no differences between males and females. Furthermore, 3 weeks on a HSD had no effect on 24 hr MAP. GFR was similar between male and female rats on either diet. However, urinary protein excretion was significantly higher in HSD fed rats compared to normal rat chow in both male (83±26 vs. 17±4 mg/day, respectively, p&lt;0.05) and female rats (106±25 vs. 6±2 mg/day, p&lt;0.05). In 8-month old rats, again there were no sex differences between animals on normal rat chow. However, MAP increased progressively in male rats after 3 weeks of HSD feeding, a change that was significantly greater than females (Δ39±6 vs Δ15±5 mmHg, p&lt;0.05). The blood pressure increase in male rats was associated with higher urinary protein excretion compared to female rats (755±118 vs. 390±48 mg/day, p&lt;0.05). HSD significantly reduced GFR in male, but not female rats (0.48±0.13 vs. 1.24±0.05 mL/min/100 g bwt, respectively, p&lt;0.05). GFR was similar between older male and female rats on normal salt diet. Summary: Our studies demonstrate that male Pkhd1 pck rats with advanced cystic kidney disease are more vulnerable to salt sensitive hypertension and renal injury than age-matched females.

Urinary monocyte chemotactic protein-1 (MCP-1) in leprosy patients: increased risk for kidney damage.

BackgroundWe aimed to evaluate urinary MCP-1 and oxidative stress through urinary malondialdehyde (MDA) in leprosy and correlate them with traditional, but less sensitive markers of renal disease.MethodsThis is a cross-sectional study of 44 patients with diagnosis of leprosy and no previous treatment. Skin smear was assessed through a bacteriological index - from 0 to 6+. Glomerular filtration rate (GFR), protein excretion rate, microalbuminuria, urinary oxidative stress, malondialdehyde (MDA) and urinary MCP-1 were measured. Also, high- sensitivity C-reactive protein (hs-CRP) was measured in the blood. Fifteen healthy subjects composed a control group.ResultsAge and gender were similar between leprosy patients and control groups. No patient had a GFR < 60 mL/min/1.73 m2 or albumin excretion rate greater than 30 mg/g-Cr. Leprosy patients had higher urinary protein excretion (97.6 ± 69.2 vs. 6.5 ± 4.3 mg/g-Cr, p < 0.001), urinary MCP-1 (101.0 ± 79.8 vs. 34.5 ± 14.9 mg/g-Cr, p = 0.006) and urinary MDA levels (1.77 ± 1.31 vs. 1.27 ± 0.66 mmol/g-Cr, p = 0.0372) than healthy controls. There was a positive correlation between urinary MCP-1 and bacteriological index in skin smears (r = 0.322, p = 0.035), urinary protein excretion (r = 0.547, p < 0.001), albumin excretion rate (r = 0.414, p = 0.006) and urinary MDA (r = 0.453, p = 0.002). After adjusting for hs-CRP, urinary MCP-1 remained correlated with albumin excretion rate (rpartial = 0.483, p = 0.007) and MDA levels (rpartial = 0.555, p = 0.001).ConclusionLeprosy patients with no clinical kidney disease have increased urinary MCP-1 mainly in lepromatous polar form. Inflammatory (MCP-1) and oxidative stress markers suggest leprosy patients are at high risk of developing kidney disease.Electronic supplementary materialThe online version of this article (doi:10.1186/1471-2334-14-451) contains supplementary material, which is available to authorized users.

Urinary protein-to-creatinine ratio versus 24-h proteinuria in the screening for nephropathy in HIV patients.

To determine the correlation between protein-to-creatinine ratio and 24-h urinary protein, proteinuria was measured in 45 patients attending a public HIV clinic in Porto Alegre, Brazil, using 24-h urinary protein excretion (24hUP) and urinary protein-to-creatinine ratio. Spearman's correlation test was done to evaluate the association between spot protein-to-creatinine ratio and 24hUP. The limits of agreement between the two methods were analysed by the Bland-Altman method. For protein excretion <1 g/day, limits (95%) of agreement of protein-to-creatinine ratio and 24hUP were +0.112 and -0.097 g/day. A strong correlation (r = 0.957) was found between protein-to-creatinine ratio and 24hUP excretion. The conclusion is that the protein-to-creatinine ratio in spot urine specimens is an accurate, convenient and reliable screening method to estimate the urinary protein excretion in HIV patients to detect abnormal urinary protein loss. Further studies are required to evaluate renal disease in HIV patients with chronic renal disease and higher urinary protein excretion.

Characteristics of the hypertensive patients with good and poor compliance to long-term salt restriction

Although salt restriction is very important for the management of blood pressure (BP), it is difficult to maintain low salt intake in hypertensive patients. The purpose of the present study is to investigate comparatively the characteristics of hypertensive patients with good or poor compliance to long-term salt restriction. Subjects included 248 hypertensive patients who underwent successful 24-h home urine collection for >5 times with the observation period of 9.4 years in average. When the subjects were categorized based on the mean 24-h urinary salt excretion during the observation period to the groups with good (<8 g/day) or poor (10 g/day or more) compliance to long-term salt restriction, subjects with poor compliance were more frequently to be male, younger and had higher BMI than those with good compliance. Although there were no significant differences in BP and the number of antihypertensive drugs between the subjects with good and poor compliance, the subjects with poor compliance were given more diuretics, more frequently complicated with diabetes mellitus and hyperuricemia and had higher urinary protein excretion than those with good compliance. Thus, strict nutritional intervention and the management of BP as well as the complicated cardiovascular risk are important for the patients with poor compliance to salt restriction.

Positive C1q staining associated with poor renal outcome in membranoproliferative glomerulonephritis

Pathogenesis and clinical prognosis of membranoproliferative glomerulonephritis (MPGN) has not yet been established. We conducted a retrospective study of 41 patients with MPGN (type I and III) and examined the renal survival. In addition, factors contributing to survival time were analyzed. Fourteen patients (34 %) were classified into the renal death group. Patients with nephrotic syndrome and positive C1q staining of glomerular deposits showed a particularly poor prognosis. Significantly higher frequency of nephrotic syndrome and higher urinary protein excretion were observed in the renal death group (p = 0.0002, p = 0.0002) than in the renal survival group. The intensity of C1q staining was positively correlated with the severity of the proteinuria (p = 0.004). Factors that influenced the survival time were positive C1q staining of glomerular deposits (p = 0.003), presence of nephrotic syndrome (p = 0.004), serum albumin (p = 0.02), and proteinuria (p = 0.04). C1q staining in glomerular deposits and nephrotic syndrome were important factors influencing the prognosis and outcome in MPGN patients. C1q deposition may play a key role in the pathogenesis of MPGN, as evidenced by numerous observations, such as induction of proteinuria.

Earlier Onset and Greater Severity of Disordered Mineral Metabolism in Diabetic Patients With Chronic Kidney Disease

OBJECTIVEDisordered mineral metabolism is a common complication of chronic kidney disease (CKD) and a novel risk factor for CKD progression, cardiovascular disease, and mortality. Although diabetes is the leading cause of CKD and is associated with worse clinical outcomes than other etiologies, few studies have evaluated mineral metabolism in CKD according to diabetes status.RESEARCH DESIGN AND METHODSUsing the Chronic Renal Insufficiency Cohort Study, we tested the hypothesis that diabetes is independently associated with lower serum calcium and higher serum phosphate, parathyroid hormone (PTH), and fibroblast growth factor 23 (FGF23).RESULTSCompared with participants without diabetes (n = 1,936), those with diabetes (n = 1,820) were more likely to have lower estimated glomerular filtration rate (eGFR), lower serum albumin, and higher urinary protein excretion (all P < 0.001). Unadjusted serum phosphate, PTH, and FGF23 levels were higher and calcium was lower among those with compared with those without diabetes (all P < 0.001). After multivariate adjustment, diabetes remained a significant predictor of serum phosphate, PTH, and FGF23 but not calcium. The eGFR cut point at which 50% of participants met criteria for secondary hyperparathyroidism or elevated FGF23 was higher in participants with diabetes compared with those without (PTH: eGFR 30–39 vs. 20–29, P < 0.001; FGF23: eGFR 50–59 vs. 40–49, P < 0.001).CONCLUSIONSDisordered mineral metabolism begins earlier in the course of CKD and is more severe among CKD patients with compared with those without diabetes. Future studies should explore mechanisms for these differences and whether they contribute to excess risks of adverse clinical outcomes among diabetic patients with CKD.

Vitamin D deficiency and persistent proteinuria among HIV-infected and uninfected injection drug users

Proteinuria occurs commonly among HIV-infected and uninfected injection drug users (IDUs) and is associated with increased mortality risk. Vitamin D deficiency, highly prevalent among IDUs and potentially modifiable, may contribute to proteinuria. To determine whether vitamin D is associated with proteinuria in this population, we conducted a cross-sectional study in the AIDS Linked to the IntraVenous Experience (ALIVE) Study. 25(OH)-vitamin D levels were measured in 268 HIV-infected and 614 HIV-uninfected participants. The association between vitamin D deficiency (<10 ng/ml) and urinary protein excretion was evaluated by linear regression. The odds of persistent proteinuria (urine protein-to-creatinine ratio >200 mg/g on two occasions) associated with vitamin D deficiency was examined using logistic regression. One-third of participants were vitamin D-deficient. Vitamin D deficiency was independently associated with higher urinary protein excretion (P < 0.05) among HIV-infected and diabetic IDUs (P-interaction < 0.05 for all). Persistent proteinuria occurred in 18% of participants. Vitamin D deficiency was associated with greater than six-fold odds of persistent proteinuria among diabetic IDUs [odds ratio (OR) 6.29, 95% confidence interval (CI) 1.54, 25.69] independent of sociodemographic characteristics, comorbid conditions, body mass index, and impaired kidney function [estimated glomerular filtration rate (eGFR) <60 ml/min per 1.73 m(2)]; no association, however, was observed among nondiabetic IDUs (OR 1.06, 95% CI 0.64, 1.76) (P-interaction <0.05). Vitamin D deficiency was associated with higher urinary protein excretion among those with HIV infection and diabetes. Vitamin D deficiency was independently associated with persistent proteinuria among diabetic IDUs, although not in nondiabetic persons. Whether vitamin D repletion ameliorates proteinuria in these patients requires further study.

Effects of uridine diphosphate glucuronosyltransferase 2B7 and 1A7 pharmacogenomics and patient clinical parameters on steady-state mycophenolic acid pharmacokinetics in glomerulonephritis

The role of pharmacogenomics, clinical and demographic parameters in pharmacokinetic predictions was evaluated in patients receiving mycophenolic acid (MPA). A cohort study design of patients with glomerulonephritis secondary to lupus nephritis and anti-neutrophil cytoplasmic antibody (ANCA) vasculitis was employed. Forty-six patients with lupus nephritis and ANCA vasculitis who were receiving MPA were recruited from the nephrology clinic. The study assessed the relative single and combined roles of genomic, clinical, and demographic characteristics on pharmacokinetic parameters using general linear models. The study focused on polymorphisms in UGT1A7, UGT2B7, and ABCB1/MDR1; all of which have limited data available concerning MPA pharmacokinetics. All patients had pharmacokinetic assessments for MPA and glucuronide metabolites (MPAG, AcMPAG). Genotyping was performed for known variants of UGTs (UGT1A9, UGT1A7, UGT2B7), and multidrug resistance protein (ABCB1/MDR1), involved in MPA disposition. Analyses included univariate and multivariate linear modeling. In univariate analyses, UGT2B7 heterozygosity (coefficient 0.3508; R (2)=0.0873) and UGT1A7 heterozygosity (coefficient 0.3778; R (2)=0.0966) predicted increased apparent oral clearance of MPA. UGT1A7 heterozygosity (coefficient -0.4647; R (2) 0.0897) predicted lower MPA trough concentrations. In multivariate assessments, higher urinary protein excretion, lower serum creatinine, and increased weight predicted greater apparent oral clearance of MPA (p < 0.0001). White race and higher serum creatinine predicted higher MPA trough concentrations (p < 0.0001). Higher exposure to MPA was predicted by decreased urinary protein excretion and increased serum creatinine. Clinical and demographic parameters were 2-4 times more important in MPA disposition than genotypes and explained 30-40% of the pharmacokinetic parameters.

High plasma hemopexin activity is an independent risk factor for late graft failure in renal transplant recipients

Chronic low-grade inflammation is involved in late renal transplant dysfunction. Recent studies suggest a role for hemopexin, an acute phase protein, in kidney damage. We investigated whether hemopexin activity (Hx) predicts graft failure in renal transplant recipients (RTRs). In 557 RTRs with functioning grafts for >or=1 year, Hx was measured in citrate-plasma. RTRs were divided according to Hx into two groups; A: sextile 1-5 (464 RTRs, 83%) and B: sextile 6 (92 RTRs, 17%). Hx [median (IQR) 11.1 (3.3-19.1) arbitrary units] was measured at 6.0 (2.6-11.5) years post-transplant. RTRs with high Hx (group B) had significantly higher urinary protein excretion (UP) and diastolic blood pressure than group A, despite significantly more prevalent use of renin-angiotensin-aldosterone system inhibitors. After follow-up [4.6 (3.8-5.2) years], incidence of graft failure in group A was 25 (5%) and in group B 14 (15%,P = 0.0009) After adjustment for high-sensitivity C-reactive protein (hsCRP), UP and other potential confounders, Hx remained an independent predictor of graft failure [HR = 2.5 (95% CI 1.2-5.3), P = 0.01]. In conclusion, elevated Hx predicts late graft failure in RTRs, independent of hsCRP and UP. This suggests that Hx measurement, next to measurement of creatinine clearance and UP, could be of value for the identification of RTRs at risk for graft failure.

Tubular Proteinuria and Glomerular Filtration 6 Years after Puumala Hantavirus-Induced Acute Interstitial Nephritis

Background/Aims: We previously found increased urinary protein excretion, glomerular filtration rate (GFR) and blood pressure in a retrospective analysis of patients with previous nephropathia epidemica (NE). Here, we evaluated the long-term outcome after NE in a prospectively recruited patient group. Methods: Proteinuria, GFR and ambulatory 24-hour blood pressure were assessed 4–7 years (mean 6) after acute NE in 37 patients, and these values were compared to those from 38 seronegative controls. Results: Six years after NE, the prevalence of elevated urinary α₁-microglobulin excretion was higher in the patients than controls (9/35 vs. 1/38; p = 0.005). The patients also had higher urinary protein excretion (0.17 ± 0.05 vs. 0.14 ± 0.04 g/day; p = 0.006), GFR (119 ± 19 vs. 109 ± 14 ml/min/1.73 m²; p = 0.016) and mean systolic (123 ± 11 vs. 117 ± 9 mm Hg; p = 0.012), nighttime systolic (109 ± 11 vs. 100 ± 9 mm Hg; p = 0.001) and nighttime diastolic blood pressure (70 ± 7 vs. 66 ± 7 mm Hg; p = 0.035) than the controls. Conclusions: These results confirm our previous findings of a higher prevalence of tubular proteinuria and increased urinary protein excretion, GFR and systolic blood pressure 6 years after acute NE.

Correlates of N-Terminal Prohormone Brain Natriuretic Peptides in African Americans with Hypertensive Chronic Kidney Disease: The African American Study of Kidney Disease and Hypertension

Background/Aims: The N-amino-terminal fragment of the prohormone B-type natriuretic peptide (NT-proBNP) is a marker of cardiac stress and elevated levels are indicative of heart failure. Few correlates of NT-proBNP levels have been identified in persons with moderate chronic kidney disease (CKD), and data from those without heart failure and from African Americans are especially limited. Methods: The African American Study of Kidney Disease and Hypertension (AASK) enrolled nondiabetic African Americans with hypertensive kidney disease (glomerular filtration rate [GFR] = 20–65 ml/min/1.73 m²) and no evidence of clinical heart failure. NT-proBNP was measured in 982 AASK participants. Results: In unadjusted analyses, GFR (r = –0.39; p < 0.001), hematocrit (r = –0.21; p < 0.001) and body mass index (BMI; r = –0.07; p = 0.04) were inversely correlated, and systolic blood pressure (r = 0.30; p < 0.001) and log UPCR (r = 0.32; p < 0.001) were positively correlated with log NT-proBNP levels. After adjustment for potential confounders, lower GFR and hematocrit and higher systolic blood pressure and protein:creatinine ratio remained significantly associated with higher NT-proBNP. Conclusion: Lower GFR and hematocrit, and higher urinary protein excretion may be associated with volume expansion in CKD. These results suggest that these processes are associated with increased NT-proBNP in CKD and may play a role in the development of heart failure.

Relationship Between Diurnal Blood Pressure Variation and Diurnal Blood Glucose Levels in Type 2 Diabetic Patients

Hypertension and hyperglycemia are established risk factors for progression of microangiopathies and macroangiopathies in type 2 diabetes mellitus. Cardiovascular risk is even more increased in diabetic patients with nocturnal nondipping or postprandial hyperglycemia. We therefore investigated the relationship between diurnal hyperglycemia and diurnal blood pressure (BP) variation in patients. One hundred seven hypertensive type 2 diabetic patients received a 24-h ambulatory BP recording. In addition, a diurnal blood glucose profile was assessed under standardized conditions on the same day: before breakfast, 2 h after breakfast, before lunch, 2 h after lunch, before dinner, 2 h after dinner, at 10:00 pm, at midnight, and 3:00 am of the following day. Degrees of fasting and postprandial hyperglycemia were calculated as area under the curve. Nocturnal nondipping occurred in 73% of our patients. Nondippers showed higher postprandial blood glucose excursions than dippers (59.5 +/- 29 v 40.7 +/- 33 mmol h/L), whereas fasting hyperglycemia or glycosylated hemoglobin (HbA(1c)) were not significantly different (56.6 +/- 49 v 54.1 +/- 44 mmol h/L and 8.8% +/- 1.9% v 8.2% +/- 1.8% for nondippers and dippers, respectively). Nocturnal nondipping was associated with a higher urinary protein excretion and lower day/night heart rate ratio. Multivariate analysis revealed postprandial hyperglycemia as an independent predictor for nondipping. Postprandial rather than fasting hyperglycemia was associated with abnormal diurnal BP variation. These observations might favor treatment regimes targeted on postprandial hyperglycemia, which could restore dipping pattern.

Renal-Protective Effect of T- and L-Type Calcium Channel Blockers in Hypertensive Patients: An Amlodipine-to-Benidipine Changeover (ABC) Study

Both strict blood pressure control and efferent artery dilatation are critical in reducing proteinuria, which in turn helps to regulate blood pressure. Benidipine, an L- and T-type calcium channel blocker, has the potential for increased effectiveness compared with L-type-dominant calcium channel blockers such as amlodipine. Therefore, we evaluated blood pressure and proteinuria after changeover from amlodipine to benidipine in poorly controlled hypertensive patients. Fifty-eight hypertensive outpatients undergoing amlodipine treatment and unable to achieve optimal blood pressure as determined by Japanese Society of Hypertension Guidelines for the Management of Hypertention (JSH 2004) were changed over to benidipine treatment. We measured blood pressure and pulse rate and assessed urinary protein excretion before and after changeover. Systolic and diastolic blood pressure dropped from 151/90 mmHg to 140/81 mmHg (p<0.0001). Mean blood pressure (p<0.0001) and pulse pressure (p=0.0069) were also reduced, but pulse rate increased from 75 bpm to 78 bpm (p=0.0047). Urinary protein excretion adjusted for urinary creatinine was reduced from 0.35 +/- 0.82 to 0.22 +/- 0.55 g/g creatinine (p=0.0119). The urinary protein reduction was observed only in patients with renin-angiotensin inhibition (p=0.0216). By switching from amlodipine to benidipine treatment, more than 80% of patients reduced their blood pressure, and more than 40% achieved optimal blood pressure. Higher urinary protein excretion (p<0.0001), lower glomerular filtration rate (p=0.0011) and presence of diabetes (p=0.0284) were correlated with reduction of urinary proteins during changeover. Taken together, our results suggest that benidipine may have greater efficacy than amlodipine in reducing blood pressure and proteinuria.

Renal Protective Effect in Hypertensive Patients: The High Doses of Angiotensin II Receptor Blocker (HARB) Study

Angiotensin receptor blockers (ARBs) are the recommended first-line antihypertensive treatment for managing chronic kidney disease, and strict blood pressure (BP) regulation is crucial for the reduction of proteinuria. Valsartan and candesartan are commonly used ARBs in Japan, with maximum permissible doses of 160 mg/day and 12 mg/day, respectively. We evaluated BP and proteinuria after changeover from the maximum dose of candesartan to the maximum dose of valsartan, in 55 poorly controlled hypertensive patients undergoing candesartan treatment who were unable to achieve optimal BP according to the Japanese Society of Hypertension Guidelines for the Management of Hypertension (JSH 2004). We measured BP and pulse rate and assessed urinary protein excretion (UPE) before and after changeover. Changeover was associated with decreases in systolic BP and diastolic BP from 158/89 mmHg to 150/86 mmHg (p<0.01). Changeover was also associated with a reduction in UPE adjusted to urinary creatinine from 0.35+/-0.19 g/g creatinine to 0.19+/-0.37 g/g creatinine (p=0.0271) in patients who had high urinary protein levels prior to changeover without significant decreases in BP (p=0.0184). According to multiple regression analysis, higher UPE (p<0.0001) and a lower glomerular filtration rate (GFR) (p=0.0011) prior to changeover were independently correlated with reduction in UPE. Our results suggest that the maximum dose of valsartan is more effective than the maximum dose of candesartan for reducing BP and proteinuria.