Urinary Protein Excretion Rate Research Articles

Sodium Thiosulfate in the Pregnant Dahl Salt-Sensitive Rat, a Model of Preeclampsia.

Aberrant production of hydrogen sulfide (H2S) has been linked to preeclampsia. We hypothesized that sodium thiosulfate (STS), a H2S donor, reduces hypertension and proteinuria, and diminishes fetal growth restriction in the Dahl salt-sensitive (S) rat, a spontaneous model of superimposed preeclampsia. In addition to a control group (n = 13), two groups received STS via drinking water at a dose of 2 g (n = 9) or 3 g per kg body weight per day (n = 8) from gestational day (GD) 10 to 20. Uterine artery resistance index was measured (GD18), urinary protein excretion rate was determined (GD19), and blood pressure and fetal outcomes were evaluated (GD20). At 2 g, STS had no effect on preeclamptic symptoms or fetal outcome. At 3 g, STS reduced maternal hypertension (121.8 ± 3.0 vs. 136.3 ± 2.9), but increased proteinuria (89 ± 15 vs. 56 ± 5 mg/24 h), and relative kidney weight (0.86 ± 0.04 vs. 0.73 ± 0.02%). Fetal/placental weight ratio was reduced (3.83 ± 0.07 vs. 4.31 ± 0.08) without affecting litter size. No differences in uterine artery flow or renal histological damage were noted across treatment groups. While these data suggest a promising antihypertensive effect that could imply prolongation of preeclamptic pregnancies, the unfavorable effects on proteinuria, kidney weight, and fetal/placental weight ratio implies that clinical implementation of STS is contra-indicated until safety for mother and child can be verified.

Accuracy of the 24-h urine protein excretion value in patients with preeclampsia: correlation with instant and 24-h urine protein/creatinine and albumin/creatinine ratios

The aim of this study was to determine the accuracy of the 24-h urine collection in preeclamptic pregnant women. This study included 65 singletons with preeclampsia and 53 singleton patients in a control-matched group. The ratio of inaccurate 24-h urine collection was measured by calculating expected urine creatinine excretion according to the proportion of pre-pregnancy weight and the lean body mass (LBM) of the patients. Comparisons were made between the accurately-collected 24-h urine protein excretion rates and the instant and 24-h urine protein/creatinine (P/Cr) and albumin/creatinine (A/Cr) ratios. Twenty-four-hour urine collection used to diagnose patients with preeclampsia was incorrectly collected 15–73.5% of the time among the patients and the control group. Instant and 24-h urine P/Cr and A/Cr ratios were correlated with total 24-h proteinuria among the patients in whom urine was collected correctly. Considering the 24-h urine P/Cr ratio, rather than the 24-h urine protein excretion value, is a better way to diagnose preeclampsia.IMPACT STATEMENTWhat is already known on this subject? Twenty-four-hour urine collection is considered as the gold standard of diagnosing proteinuria in preeclampsia, in case of the correctly collected.What do the results of this study add? Generally, in the literature the correctness of 24-h proteinuria is not questioned. However, it is actually quite important in daily practice to make the correct diagnosis of the proteinuria not to misdiagnose preeclampsia.What are the implications of these findings for clinical practice and/or further research? In this article, we aimed to show the importance of accurately collected 24-h urine in preeclampsia. We consider and advise to change the gold standard of this technique to 24-h protein/creatinine (P/Cr) ratio, in order to make correct diagnosis of the preeclampsia.

Effects of Metreleptin on Proteinuria in Patients With Lipodystrophy.

Patients with lipodystrophy have high prevalence of proteinuria. To assess kidney disease in patients with generalized (GLD) vs partial lipodystrophy (PLD), and the effects of metreleptin on proteinuria in patients with lipodystrophy. Prospective, open-label studies of metreleptin treatment in patients with GLD and PLD at the National Institutes of Health. The 24-hour urinary albumin and protein excretion rates, estimated glomerular filtration rate (eGFR), and creatinine clearance (CrCl) were measured at baseline and during up to 24 months of metreleptin treatment. Patients with increases in medications affecting outcome measures were excluded. At baseline, patients with GLD had significantly greater albuminuria, proteinuria, eGFR, and CrCl compared with patients with PLD. CrCl was above the normal range in 69% of patients with GLD and 39% with PLD (P = 0.02). With up to 24 months of metreleptin treatment, there were significant reductions in albuminuria and proteinuria in patients with GLD, but not in those with PLD. No changes in eGFR or CrCl were observed in patients with GLD or PLD during metreleptin treatment. Patients with GLD had significantly greater proteinuria than those with PLD, which improved with metreleptin treatment. The mechanisms leading to proteinuria in lipodystrophy and improvements in proteinuria with metreleptin are not clear. Hyperfiltration was also more common in GLD vs PLD but did not change with metreleptin.

Renoprotective Effect of Plantago major Against Proteinuria and Apoptosis Induced by Adriamycin in Rat

ObjectiveAdriamycin (ADR) is an important anti-cancer drug which can cause renal toxicity. Given the known anti-inflammatory and antioxidant effects of Plantago major (P. major), the aim of this study was to determine the effects of hydroalcoholic extract of P. major on ADR- induced nephropathy in rats.MethodsFifty male Wistar albino rats were randomly divided into 5 groups including: control, ADR (5 mg/kg), ADR + P. major (600 and 1200 mg/kg) and P. major (1200 mg/kg). The animals were treated with P. major extract for 5 consecutive weeks and ADR was intravenously injected on the 7th day of the study. Urine and serum samples were collected on days 0, 14, 21, 28, and 35 for the measurement of serum cholesterol and albumin levels and urine protein excretion rate. At the end of the study, the left kidneys were removed for apoptosis assessment.ResultsAdministration of ADR significantly decreased serum albumin level and increased serum cholesterol and urine protein excretion rate as well as, apoptotic cell numbers compared to the control group (P < 0.001) while had no effect on glomerular filtration rate (P > 0.05). Treatment with P. major, in both 600 and 1200 mg/kg doses, increased serum albumin level and decreased serum cholesterol concentration, urine protein excretion rate and as well as the number of apoptotic cell compared to the ADR group (P < 0.001).ConclusionOur results showed that the P. major extract effectively protects against ADR- induced nephropathy by reducing kidney apoptosis and improving renal functioning in rats.

MG132 protects against renal dysfunction by regulating Akt-mediated inflammation in diabetic nephropathy

Diabetic nephropathy (DN), the leading cause of end-stage renal disease (ESRD). To date, mounting evidence has shown that inflammation may contribute to the pathogenesis of DN. Recent reports have shown that proteasome inhibitors display cytoprotection by reducing the phosphorylation of Akt, a serine/threonine kinase, plays a critical role in cellular survival and metabolism and can crosstalk with inflammation. Therefore, we hypothesized that MG132, specific proteasome inhibitor, could provide renoprotection by suppressing Akt-mediated inflammation in DN. In vivo, male Sprague-Dawley rats were divided into normal control group (NC), diabetic nephropathy group (DN), DN model plus MG132 treatment group (MG132), and DN model plus deguelin treatment group (Deguelin)(deguelin, a specific inhibitor of Akt). In vitro, a human glomerular mesangial cell lines (HMCs) was exposed to 5.5 mmol/L glucose (CON), 30 mmol/L glucose (HG), 30 mmol/L glucose with 0.5 umol/L MG132 (MG132) and 30 mmol/L glucose with 5 umol/L deguelin (Deguelin). Compared with NC, DN showed a significant increase in the urinary protein excretion rate and inflammatory cytokines, as well as p-Akt. Compared with CON, HMCs co-cultured with HG was notably proliferated, which is in accord with α-smooth muscle actin (α-SMA) expression. These alterations were inhibited by administration of MG132 or deguelin. In conclusion, MG132 significantly inhibits the development of DN by regulating Akt phosphorylation-mediated inflammatory activation.

Mycophenolate mofetil versus cyclophosphamide for idiopathic membranous nephropathy; a double blind and randomized clinical trial

Introduction: The current treatment regimens for patients with idiopathic membranous nephropathy (MN) are based on cyclophosphamide-glucocorticoid or calcineurin inhibitor-glucocorticoid. Objectives: We evaluated whether mycophenolate mofetil (MMF) -glucocorticoid could be an option for first-line therapy among these patients. Patients and Methods: In a double-blinded, randomized and controlled clinical trial, we compared the effect of MMF with cyclophosphamide in inducing complete or partial remission (PR) among patients with nephrotic syndrome due to idiopathic MN. All of the patients in both groups also received steroid, renin-angiotensin blockers and statins. Diuretics were also used in the patients who had edema. The primary end point of our study was change in urinary protein/creatinine ratio. Results: A total of 30 patients completed the study. Around 17 patients received MMF (2 g/d) and 13 patients received intravenous or oral cyclophosphamide for 6 months. At the start of the study, no significant differences in demographic and biochemical parameters of patients including the urinary protein excretion rate between two groups (P = 0.432). The proportion of proteinuria was 5235 ± 1655 mg/24 in MMF group and 8781 ± 8741 mg/24 in the cyclophosphamide group at the beginning of the study. The rate of complete and PR were 5.9% and 52.9 in MMF group versus 16.7% and 100% in cyclophosphamide group which it is significantly lower in MMF group. Kidney function was stable in both groups during treatment. Conclusions: According to the result of our study, a 6-month therapy with MMF-glucocorticoid is not recommended for treatment of patients with nephrotic syndrome due to idiopathic MN.

Distribution of nephrologists and regional variation in the clinical severity of IgA nephropathy at biopsy diagnosis in Japan: a cross-sectional study

ObjectivesThe clinical severity of IgA nephropathy (IgAN) at the time of biopsy diagnosis differs significantly among cases. One possible determinant of any such difference is the time taken for referral...

Decreased expression of transforming growth factor-β1 and α-smooth muscle actin contributes to the protection of lotensin against chronic renal failure in rats

Background: Lotensin has been shown to have a protective function in the early stage of chronic renal failure. However, its role in the intermediate and late stages of chronic renal failure remains largely unknown. The present study aimed to investigate the role and underlying mechanism of lotensin in advanced chronic kidney disease.Methods: Female Wistar rats were randomly divided into three groups (n = 10): sham group, 5/6 nephrectomy (5/6 Nx) group, and lotensin group (oral administration of lotensin for 9 weeks following 5/6 Nx). Rats were sacrificed and pathological parameters were measured. Western blot assay and immunohistochemical staining were performed to detect the expression of transforming growth factor-β1 (TGF-β1) and α-smooth muscle actin (α-SMA) in kidney tissues.Results: Compared to the 5/6 Nx group, lotensin administration significantly decreased 5/6 Nx-induced elevation in blood urea nitrogen, serum creatinine and 24-h urinary protein excretion (UPE) rates, but markedly increased red blood cell count, plasma albumin and hemoglobin levels, along with improved renal morphology. Mechanistically, lotensin dramatically downregulated the renal expression of TGF-β1 and α-SMA induced by 5/6 Nx.Conclusions: Lotensin protects against advanced chronic kidney disease in rats with 5/6 Nx through the downregulation of TGF-β1 and α-SMA.

Inhibitor of IGF1 receptor alleviates the inflammation process in the diabetic kidney mouse model without activating SOCS2

ObjectiveTo explore the anti-inflammatory mechanism of IGF1R inhibitor in diabetic nephropathy.MethodsC57/BL6 mice were reared with high-fat diet for 8 weeks, then were injected 30 mg/kg streptozotocin intraperitoneally to induce type 2 diabetes. After 8 weeks, the type 2 diabetes nephropathy model was successfully set up the different drugs were administrated to mice with diabetes (insulin 1–2 U/day, benazepril 10 mg/kg per day intragastrically, IGF-1R inhibitor 30 mg/kg per day intragastrically). After 8 weeks drugs administration, all mice were collected the kidney tissue, measured levels of inflammatory factor (F4/80, TLR4and CD68) and fibrosis markers(αSMA, E-cadherin and SR) using immunohistochemistry and in situ hybridization.ResultsThe type 2 diabetes nephropathy model was built successfully, which along with increased urinary protein excretion rate and increased inflammatory infiltration, and the correlation was characterized by increased CD68+, F4/80+ cells and increased TLR4, αSMA, SR expression. IGF-1R inhibitors reversed this changes, but benazepril and insulin were without significant changes. The insulin decreased the expression level of IGF-1, and increased the levels of suppressor of cytokine signaling 2 (SOCS2). Benazepril and IGF-1R inhibitor were no significant changes like insulin.ConclusionInhibition of IGF1R was a more effective choice for inflammation treatment than Ben or Ins in diabetic kidney disease (DKD). The IGF1R inhibitor blocked pathological changes induced by the over-expression of IGF1 in DKD without up-regulating SOCS2 protein levels.

Comparison of the efficacy of triple blockade, double blockade and single blockade of RAAS in non diabetic chronic kidney disease

Background: Although dual blockade of the renin-angiotensin-aldosterone system with the combination of an angiotensin-converting enzyme inhibitor and angiotensin II receptor blocker is generally well established as a treatment for nephropathy, this treatment is not fully effective in some patients.Methods: A prospective observational study was done on 600 chronic kidney disease patients during July 2012 to August 2014 to compare the efficacy of triple blockade, double blockade and single blockade of renin-angiotensin-aldosterone system in non diabetic chronic kidney disease.Results: At the end of the study, 24 hours urinary protein excretion rate of group I and group III were compared by using student t-test and p value (0.0268) was found significant. Similarly, on comparing group II and group III, p value (0.0160) was again found significant.Conclusions: Triple blockade of the renin-angiotensin-aldosterone system was effective for the treatment of proteinuria in patients with non-diabetic nephropathy whose increased urinary protein had not responded sufficiently to a dual blockade.

Comparison between the efficacy of double blockade and single blockade of RAAS in diabetic kidney disease

Background: Diabetic kidney disease is associated with high morbidity and cardiovascular mortality. A number of guidelines and recommendations have been issued over the years recommending the use of renin angiotensin aldosterone system blockade in the management of diabetic kidney disease.Methods: A prospective observational study was done on 750 diabetic chronic kidney disease patients during July 2012 to August 2014 to compare the efficacy of double blockade and single blocked of renin angiotensin aldosterone system in diabetic kidney disease.Results: At the end of 24 months urinary protein excretion rate of group I and group III were compared by using student t-test and p value (0.0268) was found significant. Similarly, on comparing group II and group III, p value (0.0278) was again significant. Mean arterial blood pressure of group I and group III were statistically significant (0.0496) while comparing group II and group III, p value (0.0419) was again significant.Conclusions: The study concludes that the use of double renin angiotensin aldosterone system blockade therapy is more effective than mono-therapy at reducing albuminuria and proteinuiria, and in decreasing blood pressure at the same time not causing significant deterioration in glomerular filtration rate in diabetic kidney disease patients. Novel potassium-lowering therapies are shown to effective compensate the hyperkalemia risk associated with renin angiotensin aldosterone system blockade use in people with diabetic kidney disease, offering promise for more adequate therapy and greater renal and cardiovascular risk protection in the future.

Nephro protection property of double blockade versus single blocked of RAAS in delaying the progression of CKD

Background: Dual renin angiotensin aldosterone system blockade using angiotensin receptor blockers in combination with angiotensin converting enzyme inhibitors is reported to improve proteinuria in non-diabetic patients.Methods: A prospective observational study was done on 810 non-diabetic chronic kidney disease patients during July 2012 to August 2014 to compare the nephro protection property of double blockade and single blocked of renin angiotensin aldosterone system in delaying the progression of chronic kidney disease.Results: At the end of 24 months urinary protein excretion rate of group I and group III were compared by using student t-test and p value (0.0001) was found significant. Similarly, on comparing group II and group III, p value (0.003) was again significant. Mean arterial blood pressure of group I and group III were statistically significant (&lt;0.0496) while comparing group II and group III, p value (0.0419) was again significant.Conclusions: The study concludes that the use of double renin angiotensin aldosterone system blockade therapy is more effective than monotherapy at reducing albuminuria and proteinuiria, and in decreasing blood pressure at the same time not causing significant deterioration in glomerular filtration rate. Newer potassium lowering therapies can effectively and safely correct hyperkalemia and maintain normokalemia in patients receiving background treatment with renin angiotensin aldosterone system blockade. However, the use of new potassium binders for cardiovascular and renal risk reduction with combined renin angiotensin aldosterone system blockade therapy will require phase III trials.

Meta analysis of curative effect of safflower yellow injection on the elderly with early diabetic nephropathy

Objective To systematically evaluate the effects of safflower yellow injection on the treatment of senile early diabetic nephropathy. Methods All databases from January 2000 to June 2017, including the Chinese biomedical literature database (CBM), Chinese Journal Full-text Database (CNKI), Chinese PSTP VIP (VIP) and Wanfang database (WFSD), were searched on the safflower yellow injection for treatment of senile early diabetic nephropathy in randomized controlled trail.Literatures were selected based on inclusion and exclusion standards defined in advance, and their quality was evaluated.The valid data were retrieved and a Meta analysis of the urinary albumin excretion rate and serum creatinine was undertaken using RevMan5.3 Software. Results 16 articles with 1 048 cases were internalized into the study.Among 1 048 cases, 525 cases were treated with safflower yellow injection added to general comprehensive treatment (treatment group), and 523 cases with general comprehensive treatment (control group). The results of meta analysis showed that urinary protein excretion rate 〔WMD (weighted mean difference)=-0.74, 95%CI: -0.85 to -0.63; Z=13.15, P=0.000〕 and serum creatinine level 〔WMD=-4.30, 95%CI: -6.54 to -2.06, Z=3.77, P=0.002〕 were significantly lower in safflower yellow injection added to conventional treatment than in conventional treatment. Conclusions Safflower yellow pigment injection is superior to conventional treatment for senile early diabetic nephropathy, but there are few high quality studies and the sample size is limited, therefore more studies are needed. Key words: Diabetic nephropathies; Meta-analysis

Deletion Variants of CFHR1 and CFHR3 Associate with Mesangial Immune Deposits but Not with Progression of IgA Nephropathy.

Activation of complement through the alternative pathway has a key role in the pathogenesis of IgA nephropathy (IgAN). Large, international, genome-wide association studies have shown that deletion of complement factor H-related genes 1 and 3 (CFHR3,1Δ) is associated with a reduced risk of developing IgAN, although the prognostic value of these deletions in IgAN remains unknown. Here, we compared the renal outcomes of patients with IgAN according to their CFHR3,1Δ genotype. This retrospective, monocentric cohort study included 639 white patients with biopsy-proven IgAN since 1979 (mean age at diagnosis, 40.1 years; median follow-up, 132 months). We determined the number of CFHR3 and CFHR1 gene copies by quantitative PCR and collected clinical and biologic data by reviewing the patients' medical records. In all, 30.5% of the patients were heterozygous and 4% were homozygous for CFHR3,1Δ We did not detect an association between CFHR3,1Δ and age, eGFR, urinary protein excretion rate, or the presence of hypertension or hematuria at the time of diagnosis. The mean intensities of immune IgA, IgG, and C3 deposits were lower in the group with heterozygous or homozygous gene deletions than in those with no deletion. However, CFHR3,1Δ did not associate with progression to stage 3 CKD or renal death. In conclusion, the CFHR3,1Δ genotype did not associate with progression toward CKD stages 3 and 5 in our white population of patients with IgAN, although it did associate with a reduced level of glomerular immune deposits.

The relationship between serum Sirt1 and EGR1 and other inflammatory cytokines in type 2 diabetic patients with different stages of diabetic nephropathy

Objective To investigate changes of serum silent information regulator 1 (Sirt1) and inflammatory cytokines in type 2 diabetes patients with different stages of diabetic nephropathy. To explore the relationship between serum Sirt1 level and inflammatory cytokines in type 2 diabetic patients with different urinary albumin excretion rates. Methods A total of 436 cases with type 2 diabetes were divided into three groups: normoalbuminuric , microalbuminuric , and macroalbuminuric . Serum Sirt1, hypoxia-inducible factor-1α (HIF-1α), early growth response protein 1 (EGR1), insulin-like growth factors -Ⅰ (IGF-Ⅰ), and monocyte chemotactic protein-1 (MCP-1) were determined by enzyme-linked immunosorbent assay (ELISA). Results The levels of serum Sirt1 in type 2 diabetes patients were significantly lower than that in control group, and with the increase of urinary protein excretion rate, the levels of serum Sirt1 in group D1, D2 and D3 were decreased gradually (P<0.01). Compared to control, serum inflammatory cytokines (HIF-1α, EGR1, IGF-Ⅰ, and MCP-1) levels were significantly increased in type 2 diabetic patients and gradually increased in the patients of D1, D2 and D3 groups (P<0.01). Furthermore, Serum Sirt1 was negatively correlated with the levels of inflammatory cytokines. Age, duration, fasting blood glucose (FBG), fasting insulin (FINS), homeostasis model assessment insulin resistance index (HOMA-IR), glycosylated hemoglobin (HbA1c), low density lipoprotein (LDL), total cholesterol (TC), triglyceride (TG), serum creatinine (Scr), blood urea nitrogen (BUN), uric acid (UA), HIF-1α, EGR1, IGF-Ⅰ, and MCP-1 were positively correlated with Ln Koc of urinary albumin to creatinine ratio (P<0.05); and Sirt1 were negatively correlated with Ln(ACR) (P<0.01). HIF-1α, MCP-1, IGF-Ⅰ, duration, BUN, Sirt1, UA, LDL, and EGR1 were independent factors that significantly influenced Ln(ACR) (P<0.05). Conclusions Serum Sirt1 might be a new target for the treatment of diabetic nephropathy. Enhancing serum Sirt1 levels might have a role in delaying the progression of diabetic nephropathy. Key words: Diabetes mellitus, type 2/ME; Albumins/ME; Histone deacetylases/ME; Early growth response protein 1/ME; Hypoxia-inducible factor 1/ME; Insulin-like growth factor Ⅰ/ME; Chemokine CCL2/ME

Plasma Exchange as an Adjunctive Therapy for Crescentic IgA Nephropathy

Background: Crescentic IgA nephropathy (CreIgAN) has a poor prognosis despite aggressive immunosuppressive therapy. The efficacy of plasma exchange (PE) in CreIgAN is not well defined. Methods: Twelve patients with severe CreIgAN who received PE as addition to routine immunosuppressive therapy, followed for more than 6 months, were involved. Twelve matched historical controls who received immunosuppressive therapy alone were selected by propensity score matching. Renal survival, plasma IgA-IgG complex and active complement products were assessed. Results: Nine men and 3 women received a median of 7 PE courses (range 5-10). Their baseline urine protein excretion rate was 5.8 (4.5-8.7) g/day, and their serum creatinine level was 705.3 ± 296.4 μmol/l. During a mean follow-up of 15.6 months (6-51 months), 6 of the 12 PE group patients were free of dialysis, while all the control patients were dialysis dependent (6 of 12 vs. 0 of 12, p = 0.014). In the PE group, dialysis had to be restarted for 1 patient owing to the development of severe pneumonia and pulmonary failure. PE was associated with a higher kidney survival rate (log rank test, p = 0.026) during follow-up. It also significantly decreased plasma IgA-IgG complex levels (pre-PE: 85.3 ± 25.9% vs. post-PE: 38.4 ± 12.4%, p < 0.001) and plasma and urinary active complement product levels, including C3a, C5a and soluble C5b-9. The latter levels remained low until the last follow-up. Conclusion: This study indicated that PE could increase renal recovery rates in severe CreIgAN.

Quantification of angiotensin II-regulated proteins in urine of patients with polycystic and other chronic kidney diseases by selected reaction monitoring.

BackgroundAngiotensin-II (Ang II) mediates progression of autosomal-dominant polycystic kidney disease (ADPKD) and other chronic kidney diseases (CKD). However, markers of kidney Ang II activity are lacking. We previously defined 83 Ang II-regulated proteins in vitro, which reflected kidney Ang II activity in vivo.MethodsIn this study, we developed selected reaction monitoring (SRM) assays for quantification of Ang II-regulated proteins in urine of ADPKD and CKD patients. We demonstrated that 47 of 83 Ang II-regulated transcripts were differentially expressed in cystic compared to normal kidney tissue. We then developed SRM assays for 18 Ang II-regulated proteins overexpressed in cysts and/or secreted in urine. Methods that yielded CV ≤ 6 % for control proteins, and recovery ~100 % were selected. Heavy-labeled peptides corresponding to 13 identified Ang II-regulated peptides were spiked into urine samples of 17 ADPKD patients, 9 patients with CKD predicted to have high kidney Ang II activity and 11 healthy subjects. Samples were then digested and analyzed on triple-quadrupole mass spectrometer in duplicates.ReslutsCalibration curves demonstrated linearity (R2 > 0.99) and within-run CVs < 9 % in the concentration range of 7/13 peptides. Peptide concentrations were normalized by urine creatinine. Deamidated peptide forms were monitored, and accounted for <15 % of the final concentrations. Urine excretion rates of proteins BST1, LAMB2, LYPA1, RHOB and TSP1 were significantly different (p < 0.05, one-way ANOVA) between patients with CKD, those with ADPKD and healthy controls. Urine protein excretion rates were highest in CKD patients and lowest in ADPKD patients. Univariate analysis demonstrated significant association between urine protein excretion rates of most proteins and disease group (p < 0.05, ANOVA) as well as sex (p < 0.05, unpaired t test). Multivariate analysis across protein concentration, age and sex demonstrated good separation between ADPKD and CKD patients.ConclusionsWe have optimized methods for quantification of Ang II-regulated proteins, and we demonstrated that they reflected differences in underlying kidney disease in this pilot study. High urine excretion of Ang II-regulated proteins in CKD patients likely reflects high kidney Ang II activity. Low excretion in ADPKD appears related to lack of communication between cysts and tubules. Future studies will determine whether urine excretion rate of Ang II-regulated proteins correlates with kidney Ang II activity in larger cohorts of chronic kidney disease patients.Electronic supplementary materialThe online version of this article (doi:10.1186/s12014-016-9117-x) contains supplementary material, which is available to authorized users.

Dipeptidyl Peptidase IV Inhibition Exerts Renoprotective Effects in Rats with Established Heart Failure.

Circulating dipeptidyl peptidase IV (DPPIV) activity is associated with worse cardiovascular outcomes in humans and experimental heart failure (HF) models, suggesting that DPPIV may play a role in the pathophysiology of this syndrome. Renal dysfunction is one of the key features of HF, but it remains to be determined whether DPPIV inhibitors are capable of improving cardiorenal function after the onset of HF. Therefore, the present study aimed to test the hypothesis that DPPIV inhibition by vildagliptin improves renal water and salt handling and exerts anti-proteinuric effects in rats with established HF. To this end, male Wistar rats were subjected to left ventricle (LV) radiofrequency ablation or sham operation. Six weeks after surgery, radiofrequency-ablated rats who developed HF were randomly divided into two groups and treated for 4 weeks with vildagliptin (120 mg/kg/day) or vehicle by oral gavage. Echocardiography was performed before (pretreatment) and at the end of treatment (post-treatment) to evaluate cardiac function. The fractional area change (FAC) increased (34 ± 5 vs. 45 ± 3%, p < 0.05), and the isovolumic relaxation time decreased (33 ± 2 vs. 27 ± 1 ms; p < 0.05) in HF rats treated with vildagliptin (post-treatment vs. pretreatment). On the other hand, cardiac dysfunction deteriorated further in vehicle-treated HF rats. Renal function was impaired in vehicle-treated HF rats as evidenced by fluid retention, low glomerular filtration rate (GFR) and high levels of urinary protein excretion. Vildagliptin treatment restored urinary flow, GFR, urinary sodium and urinary protein excretion to sham levels. Restoration of renal function in HF rats by DPPIV inhibition was associated with increased active glucagon-like peptide-1 (GLP-1) serum concentration, reduced DPPIV activity and increased activity of protein kinase A in the renal cortex. Furthermore, the anti-proteinuric effect of vildagliptin treatment in rats with established HF was associated with upregulation of the apical proximal tubule endocytic receptor megalin and of the podocyte main slit diaphragm proteins nephrin and podocin. Collectively, these findings demonstrate that DPPIV inhibition exerts renoprotective effects and ameliorates cardiorenal function in rats with established HF. Long-term studies with DPPIV inhibitors are needed to ascertain whether these effects ultimately translate into improved clinical outcomes.

Effects of Polyethylene Glycol on Renal Functional Parameters in Rats

Background: The use of polyethylene glycol (PEG) is increasing day by day in various purposes by pharmaceutical industries as well as its anti-colonic cancer effects in clinical diseases.Objective: To evaluate the effects of PEG on renal functional and morphological parameters in rats.Methods: Six weeks age matched Sprague-Dawley rats were treated with either vehicle (2 mL of 5% dist. water in saline/kg, i.p. twice daily, n=6), or PEG 400 (2 mL of 5% PEG 400 in saline/kg, i.p. twice daily, n=6). After three weeks treatment all rats were subjected to uninephrectomy (UNX) and continued the treatment for further two weeks. Unpaired ‘t’ test was used for statistical significance.Results: Before and after uninephrectomy intraperitoneal injection of PEG 400 did not alter systolic blood pressure, renal blood flow, body weight gain and twenty-four hours urine protein excretion rate compared to control rats, however, three weeks after UNX urine protein excretion rate were increased in both groups and was not significant. Intraperitoneal PEG 400 treatment significantly increased twenty-four hours water intake and urine volume compared to control rats. Histopathological evaluation of renal section by periodic acid Schiff staining, Massen’s trichrom staining and desmin staining did not show any morphological changes compared to control rats.Conclusion: Renal functional and morphological status did not show significant alterations after intraperitoneal injection of PEG for three weeks of uninephrectomized rats. Therefore, present finding suggested that PEG 400 may not have any adverse effects on renal functional as well as morphological parameters in rat.Bangladesh Soc Physiol. 2015, December; 10(2): 61-66

A comparative study of spot urine versus 24 hour urine in assessment of proteinuria in varying degree of renal dysfunction

Background: Proteinuria is a condition in which urine contains an excess amount of proteins. The gold standard test for evaluation of proteinuria is 24 hour urinary protein estimation which is a cumbersome process. The rate of urinary protein excretion remains variable and no standard values have been established for timed samples. However since it remains a very simple procedure to perform, evaluation of the predictive nature of the test in comparison to the 24 hour method is necessary. The aim of the study was to compare the 24 hour urinary protein excretion expected from 7 am and 7 pm spot urine protein creatinine ratio with the estimated urine protein from a 24 hours urinary sample collection. Methods: 55 patients with persistent dipstick positive proteinuria with varying degrees of renal dysfunction were included in this study. Two urine samples were collected, one in the early morning (around 7 am) and other in the evening (around 7 pm). Both samples were used to estimate protein – creatinine ratio and calculate expected 24 hours urinary protein excretion. 24 hours urine protein estimation was done simultaneously and compared. Results: There was significant positive correlation with both the samples though the better correlation was seen in early morning urine sample than evening sample (r = 0.931 for 7am sample & r = 0.872 in 7 pm sample; p <0.01). The maximum correlation was seen in patients with normal/mild renal dysfunction and non nephrotic range proteinuria while it was lesser in patients with moderate/severe renal dysfunction and nephrotic range proteinuria. Conclusions: Spot Urine Protein Creatinine Ratio may be used as an alternative for the 24 hour urinary protein excretion as it has a good correlation with the longer method. The early morning sample may be a preferable one.