Risk Of Progression To Renal Disease Research Articles

Ramadan Fasting in Chronic Kidney Disease Patients: A Descriptive Observational Study

Background: According to Islamic rules, a Muslim is requested to abstain from food, water, smoking, medications, and sexual activities from dawn until dusk, every day during the month of Ramadan. While Islam rules allow patients with appreciable illnesses not to fast, many Muslims, with chronic diseases, tend to stick to fasting, even against medical advice. However, there is no consensus among treating physicians regarding the fasting of Ramadan of patients in various stages of chronic kidney disease (CKD), especially those who insist on fasting regardless of their health problems.
 Aim of the Work:We aimed to observe the practice of Ramadan fasting of CKD patients of different disease stages and its effect on CKD progression.
 Methods and Subjects:The study observed sixty-three patients who were followed regularly at the Nephrology Outpatient Clinic in Mansoura Military Hospital, before, during, and after the month of Ramadan during summer in the years 2016-2019 to evaluate the effect of fasting on the patients and their kidneys. The study comprised two groups that comprised fifty fasting patients and thirteen in non -fasting group.
 Results:The examined CKD patients included 47 males and 16 females who comprised 50 patients who practised fasting and 13 patients who did not fast the months of Ramadan according to their own will. Their ages ranged between 27 and 77 years. Forty-nine patients did not progress to end-stage renal disease (ESRD), while the remaining fourteen patients ended with dialysis during the study.Neither urea nor creatinine changes had statistically significant differences between patients who had and who had not fasted. In addition, differences in creatinine slope values between those who fasted did not show any statistical significance. Fourteen of the studied patients progressed to the need for dialysis; their mean age was 62 years. Of them, those who fasted included 3 patients of stage 4 and 6 patients of stage 5. Furthermore, the frequency of patients who started dialysis directly after Ramadan (six patients; 66.7%) were lower in the fasting group. Of the studied patients, seven had renal stones and opted to fast. All of them experienced occasional attacks of loin pain that increased during the first two weeks of fasting but decreased in the last two weeks of the month of Ramadan.
 Conclusion: Compared to non-fasting, Ramadan fasting does not cause a significant extra risk of renal disease progression.

261 IMPACT OF BASELINE KIDNEY FUNCTION ON SGLT2 INHIBITOR EFFECTS ON RENAL AND HEART FAILURE OUTCOMES: A SYSTEMATIC REVIEW AND META-ANALYSIS OF RANDOMIZED CONTROLLED TRIALS

Abstract Background Sodium-glucose cotransporter-2 inhibitors (SGLT2i) have been shown to reduce renal and heart failure (HF) events in people with and without diabetes. Although their glycemic efficacy is dependent on kidney function, it remains unclear to what extent baseline kidney function influences the magnitude of SGLT2i cardiorenal effects. Methods We conducted a systematic review and meta-analysis of randomized, placebo-controlled trials testing the effects of SGLT2i on renal and CV outcomes (PROSPERO registration number CRD42022325976). Efficacy outcomes, stratified by five estimated glomerular filtration rate (eGFR) categories, included progression of renal disease (as defined in each trial), a composite HF outcome (defined as CV death or hospitalization/urgent visit for HF), and all-cause mortality. Results Eleven trials testing five SGLT2i (empagliflozin, dapagliflozin, canagliflozin, ertugliflozin and sotagliflozin) in 77,541 participants were included. The majority of participants (39.8%) had eGFR values between 60 and 90 ml/min/1.73m2, with only 1.3% having advanced kidney disease (eGFR between 20 and 30 ml/min/1.73m2). Overall, SGLT2i reduced the risk of renal disease progression by 41% (HR 0.59, 95%CI 0.54–0.65, p<0.001) and the risk of HF outcomes by 22% (HR 0.78, 95%CI 0.73–0.83, p<0.001). Meta-regression analyses showed a significant direct relationship between baseline eGFR and the magnitude of SGLT2i renal protection (p=0.040). The greatest relative risk reduction was in participants with eGFR values ≥90 ml/min/1.73m2 (HR 0.43, 95%CI 0.32–0.58) and the smallest was in those with an eGFR between 30 and 45 ml/min/1.73m2 (HR 0.64, 95%CI 0.55–0.76). Conversely, the HF outcome showed a non-significant trend to greater benefit in participants with lower eGFR categories (p=0.086). The greatest relative risk reduction was in those with an eGFR between 20 and 30 ml/min/1.73m2 (HR 0.68, 95%CI 0.48–0.96, p=0.026) and the smallest was in those with an eGFR ≥90ml/min/1.73m2 (HR 0.87, 95%CI 0.56–1.35, p=0.52). Conclusions SGLT2i reduce risk of renal disease progression and HF outcomes for all eGFR subgroups. However, the opposite trends for the influence of baseline kidney function between renal and HF outcomes suggest different SGLT2i mechanisms for renal and cardiac protection.

Statins and renal disease progression, ophthalmic manifestations, and neurological manifestations in veterans with diabetes: A retrospective cohort study

Statins increase insulin resistance, which may increase risk of diabetic microvascular complications. Little is known about the impact of statins on renal, ophthalmologic, and neurologic complications of diabetes in practice. The objective of this study was to examine the association of statins with renal disease progression, ophthalmic manifestations, and neurological manifestations in diabetes. This is a retrospective cohort study, new-user active comparator design, that included a national Veterans Health Administration (VA) patients with diabetes from 2003 to 2015. Patients were age 30 years or older and were regular users of the VA with data encompassing clinical encounters, demographics, vital signs, laboratory tests, and medications. Patients were divided into statin users or nonusers (active comparators). Statin users initiated statins and nonusers initiated H2-blockers or proton pump-inhibitors (H2-PPI) as an active comparator. Study outcomes were: 1) Composite renal disease progression outcome; 2) Incident diabetes with ophthalmic manifestations; and 3) Incident diabetes with neurological manifestations. Out of 705,774 eligible patients, we propensity score matched 81,146 pairs of statin users and active comparators. Over a mean (standard deviation) of follow up duration of 4.8 (3) years, renal disease progression occurred in 9.5% of statin users vs 8.3% of nonusers (odds ratio [OR]: 1.16; 95% confidence interval [95%CI]: 1.12-1.20), incident ophthalmic manifestations in 2.7% of statin users vs 2.0% of nonusers (OR: 1.35, 95%CI:1.27-1.44), and incident neurological manifestations in 6.7% of statin users vs 5.7% of nonusers (OR: 1.19, 95%CI:1.15-1.25). Secondary, sensitivity, and post-hoc analyses were consistent and demonstrated highest risks among the healthier subgroup and those with intensive lowering of LDL-cholesterol. Statin use in patients with diabetes was associated with modestly higher risk of renal disease progression, incident ophthalmic, and neurological manifestations. More research is needed to assess the overall harm/benefit balance for statins in the lower risk populations with diabetes and those who receive intensive statin therapy.

Renal effectiveness and safety of the sodium-glucose cotransporter-2 inhibitors: a population-based cohort study

IntroductionTo assess the comparative effectiveness and safety of renal-related outcomes associated with sodium-glucose cotransporter-2 inhibitors (SGLT2-i) initiation among patients with type 2 diabetes using real-world data.Research design and methodsWe conducted...

Blood pressure level and progression of renal disease in children with Х-linked Alport syndrome

AIM : The aim was to determine the significance of blood pressure level on progression of renal failure in children with X-linked Alport syndrome. PATIENTS AND METHODS . eGFR, urine proteine (mg/m 2 /day), mean day blood pressure – MBP (normalized for sex, age, height) were assessed in retrospective single center study. RESULTS . A 69 children (age 9.49±4.18 years, М/ F=47/22, eGFR=109±17.36 ml/min/1,73m 2 ) were followed for 4[3;5] years. The 27 pts (М/F=13/14) had MBP<50‰, the 33 children (М/F=25/8) – MBP 50-90‰ and pts (М/F=9/0) – MBP≥90‰. Rate of eGFR decline was higher in male (-3[-0.8;-4.7] vs 0.2[-0.4;2]; χ 2 = 21.15587, p = 0.0067), in pts with MBP ≥90‰ (0.65[-2.65;2] vs -2.3[-6;2.3] vs -3[-7.5;-1.8] in 1st, 2 nd and 3 groups, respectively; р 1,3 =0.0091) and proteinuria (-2.5[-7;0.5] vs 0.2[-4;3]; p=0.0018). Patients with blood hypertension had high risk of renal failure (OR=5.33, 95 % CI 1.75;16.22), especially in cases of proteinuria (OR=7.08, 95 % CI 2.46;20.39). MBP<50‰ associated with low risk of renal disease progression (OR=0.83, 95 % CI 0.31;2.2), especially in boys and proteinuric patients. The male gender and proteinuria are independent risk factors for eGFR decline. CONCLUSIONS . MBP≥90‰ is associated with renal disease progression, especially in case of proteinuria; the MBP<50‰ reduced the risk of eGFR decline in male and proteinuric patients with Alport syndrome; the male gender and proteinuria are independent risk factors for renal disease progression in children with Alport syndrome.

Derepression of glomerular filtration, renal blood flow and antioxidant defence in patients with type 2 diabetes at high-risk of cardiorenal disease

BackgroundThe role of antioxidant status on microvascular blood flow and glomerular filtration (eGFR) in patients with type 2 diabetes and hypertension whose risk of progressive renal disease varies by ethnicity is unknown. MethodsAdult, non-Caucasian (n = 101) and Caucasian (n = 69) patients with type 2 diabetes, hypertension and/or microalbuminuria and an eGFR > 45 mL/min/1.73 m2 were randomised to receive 400 IU vitamin E and/or 20 μg selenium daily or matching placebo. eGFR (CKD-EPI) was measured at baseline, 3,6 and 12 months and renal blood flow by contrast-enhanced ultrasonography in a sub-group (n = 9) at baseline and 3 months by assessing the area under the time intensity curve (TIC). Circulating glutathione peroxidase 3 (GPx-3) activity was measured as a biomarker of oxidative defence status. ResultsThe time to change in eGFR was shortest with combined vitamin E and selenium than usual care (5.6 [4.0–7.0] vs 8.9 [6.8–10.9 months]; p = 0.006). Area under the TIC was reduced compared to baseline (38.52 [22.41–90.49] vs 123 [86.98–367.03]dB.s; P ≤ 0.05 and 347 [175.88–654.92] vs 928.03 [448.45–1683]dB.s; P ≤ 0.05, respectively] at 3 months suggesting an increase in rate of perfusion. The proportional change in eGFR at 12 months was greater in the group whose GPx-3 activity was above, compared with those below the cohort median (360 U/L) in the non-Caucasian and the Caucasian groups (19.1(12.5–25.7] % vs 6.5[-3.5 to 16.5] % and 12.8 [0.7 to 24] % vs 0.2 [-6.1 to 6.5] %). ConclusionIn these patients with type 2 diabetes and early CKD, antioxidant treatment derepresses renal blood flow and a rise in eGFR correlated directly with GPx-3 activity. SignificanceDiabetes mellitus is the world's leading cause of end-stage renal disease which has a predilection for black and minor ethnic groups compared with Caucasians. The differences in risk despite the benefits of conventional care may be related to oxidative stress. We found that glomerular filtration and renal blood flow is suppressed when renal function is preserved in high-risk patients with type 2 diabetes. Conventional care supplemented with selenium - the co-factor for glutathione peroxidase-3 (GPx-3) - improves renal perfusion and increase glomerular filtration according to host antioxidant defence determined by GPx-3 activity. Circulating GPx-3 activity warrants further investigation as a novel biomarker of reversible haemodynamic changes in early diabetic kidney disease to better enable targeting of renoprotective strategies.

P0355FAMILY HISTORY OF COMPLEX TRAITS IN THE CUREGN COHORT: ASSOCIATIONS WITH RENAL FUNCTION, COMORBIDITY BURDEN AND DISEASE PROGRESSION

Abstract Background and Aims Family history (FHx) of complex traits may reflect shared genetic/environmental risk. Few studies suggest associations with increased risk of comorbidities and worsening renal function, but this has not been examined in primary glomerulopathies (GNs). Herein, we studied the association of FHx of complex traits with presentation patterns, comorbidities and disease progression in a prospective cohort of patients with primary GN. Method The Cure Glomerulopathy Networ (CureGN) is a prospective multi-center observational study of GN patients (N=2474) affected by biopsy-proven Focal Segmental Glomerulosclerosis (FSGS), Minimal Change Disease (MCD), Membranous Nephropathy (MN) and IgA Nephropathy/Vasculitis (IgAN/V). Associations of self-reported FHx of diabetes (DM), coronary artery disease (CAD), cancer (C), clotting disorders (CD), and autoimmune diseases (AD) with eGFR, UPCR at diagnosis, and comorbidities prevalence were studied using linear and logistic regression models adjusted for age, sex, ethnicity, race, BMI and other relevant clinical covariates. Associations between FHx and ESRD/40%eGFR reduction were investigated with multivariate Cox models. Results FHx of DM was associated with lower eGFR and higher UPCR at diagnosis in the entire cohort (p=0.006 and p=0.03), lower eGFR in FSGS (p=0.02) and higher UPCR in IgAN/V (p=0.01). Regarding comorbidity burden (Table 1), FHx of DM was associated with higher prevalence of DM, heart failure and infections requiring hospitalization, FHx of C with cancer, FHx of CD with higher prevalence of thrombosis and FHx of AD with inflammatory bowel, celiac diseases, asthma and drug allergies. At the survival analysis adjusted for age, sex, ethnicity, race, BMI, diagnosis group, eGFR and UPCR at diagnosis, DM, hypertension, use of immunosuppressants and RAAS-inhibitors, FHx of DM was associated with higher risk of the composite outcome of ESRD/40%eGFR reduction in the entire cohort (HR 1.39, 95%CI 1.07-1.81, p=0.01), and specifically in FSGS (HR 1.76, 95%CI 1.08-2.85, p=0.02) and in the paediatric subgroup (HR 1.98, 95%CI 1.04-3.80, p=0.04). Conclusion FHx of complex traits are associated with higher prevalence of specific comorbidities. FHx of DM identifies patients with lower eGFR at diagnosis, higher prevalence of infections and higher risk of renal disease progression. These findings, which need to be confirmed in other cohorts, suggest that FHx could be an additional useful parameter for risk stratification and management of primary GN.

P1017A RANDOMIZED, PLACEBO-CONTROLLED MULTICENTER STUDY OF THE EFFECTS OF 12 WEEKS OF SODIUM ZIRCONIUM CYCLOSILICATE (SZC) ON ALBUMINURIA (UACR) IN PATIENTS WITH TYPE 2 DIABETES AND HYPERKALEMIA

Abstract Background and Aims Hyperkalemia is a frequent challenge in the treatment of type 2 diabetes and chronic kidney disease. It often leads to suboptimal dosing or discontinuation of renin-angiotensin (RAS) blockade, thus increasing the risk of renal disease progression. Furthermore, epidemiological findings indicate that high potassium levels impair the renoprotective effect of RAS blockade. We want to test whether adjunctive treatment with sodium zirconium cyclosilicate (SZC) a new treatment for hyperkalemia, improves the effect of standard RAS blocking treatment as measured by urinary albumin creatinine ratio (UACR) in individuals with type 2 diabetes. Method Randomized, double-blind placebo-controlled multicenter study with 2 sites in Denmark and 3 sites in Sweden. Individuals (n=100) with type 2 diabetes (age 18-85), persistent macroalbuminuria (UACR≥ 200 mg/g) on chronic RAS blocking treatment and documented hyperkalemia (plasma potassium ≥ 5.0 mmol/L at least once within 90 days of inclusion) will be enrolled in the study. Participants with plasma potassium &amp;gt;5.0 mmol/L at the last assessment before randomization will be randomized to receive SZC 10 g or placebo three times a day (tid) for 2 days followed by SZC 5g or placebo once a day (qd). Participants with serum potassium ≤ 5.0 mmol/L will be randomized to receive SZC qd or placebo qd.UACR will be measured in three consecutive morning spot urine collections at baseline and the end of study after 12 weeks of treatment with Lokelma or placebo. Results The primary outcome is change in geometric mean UACR from baseline to end of studySecondary outcomes include changes in estimated glomerular filtration rate (eGFR, calculated by CKD-EPI formula) and 24-h urinary sodium and potassium excretion.In an exploratory analysis the long-term effect of potassium reduction will be modelled using the PRE-SCORE risk calculator. In addition, changes in plasma aldosterone levels will be assessed, and safety will be monitored according to good clinical practice. Conclusion This study will test the concept of SZC as an add-on therapy to improve the renoprotective effect of standard RAS blocking treatment. This could provide future potential for keeping more individuals on optimal dosing of RAS blockade.

Comparative effect of allopurinol and febuxostat on long-term renal outcomes in patients with hyperuricemia and chronic kidney disease: a systematic review.

Patients with chronic kidney disease (CKD) are more likely to develop hyperuricemia and gout. Allopurinol and febuxostat are the most commonly used urate-lowering therapies with established safety and efficacy in CKD patients. The objective of the systematic review is to assess the long-term renal outcomes of allopurinol compared with febuxostat in patients with hyperuricemia and CKD or kidney transplantation. PubMed MEDLINE, Embase, Web of Science, Scopus, and Cochrane CENTRAL databases were searched from inception to December 2019 using the key terms "allopurinol," "febuxostat," "xanthine oxidase inhibitors," "gout suppressants," "hyperuricemia," "gout," "chronic renal insufficiency," and "kidney transplantation." Studies with follow-up duration ≥ 12months were included. Risk of bias was assessed using the Cochrane Risk Of Bias In Non-randomized Studies-of Interventions (ROBINS-I) tool. Three retrospective observational studies with follow-up duration ranging from 1 to 5years were reviewed. Febuxostat patients had a significantly higher estimated glomerular filtration rate, reduced risk for renal disease progression, and reduced serum uric acid levels compared with allopurinol patients. All studies had a serious risk of bias. Febuxostat may be more renoprotective than allopurinol in patients with both hyperuricemia and CKD based on evidence from small long-term retrospective studies with serious risk of bias. More methodologically rigorous studies are needed to determine the clinical applicability of these results.

Pulling the Hood off Genetic Susceptibility to Hypertensive Renal Disease

Pulling the Hood off Genetic Susceptibility to Hypertensive Renal Disease

Circulating TNF receptors and risk of renal disease progression, cardiovascular disease events and mortality in patients with diabetes: a systematic review and meta-analysis.

Inflammation plays an important role in the pathogenesis of diabetes complications. This study aims to assess the association between circulating inflammatory biomarkers TNF receptors (TNFRs) and the risk of renal disease progression, cardiovascular disease (CVD) events, and mortality in patients with diabetes. PubMed and Embase databases were comprehensively searched up to March 2019. Data were extracted independently by two reviewers. A random effects model was performed for the pooled analyses. Five studies in 3316 subjects assessed TNFRs with renal disease in patients with type 1 diabetes and showed both TNFR-1 and TNFR-2 were consistently associated with the renal outcomes. Fourteen studies in 7696 subjects evaluated TNFRs in patients with type 2 diabetes. The pooled risk ratio per doubling increase in TNFR-1 and TNFR-2 for renal disease progression was more than two (2.64 [1.98, 3.52] and 2.23 [1.69, 2.94]). The subgroup analyses and sensitivity analyses further illustrated these results of renal outcome and its robustness. Moreover, higher TNFR-1 and TNFR-2 was also significantly associated with CVD events and mortality in patients with type 2 diabetes. Circulating TNFR-1 and TNFR-2 are independently associated with higher risk of renal disease progression, CVD events, and mortality in patients with diabetes and might contribute to the clinical risk assessment in the future.

Who do we discharge from renal clinic and what does it mean for primary care?

It is unclear whether discharging patients from renal clinic to primary care is safe. To determine the characteristics, primary care monitoring and renal outcomes of patients discharged from renal clinic. A retrospective study of 2236 adults discharged from a tertiary renal clinic between 2013-2018. Patient demographics, primary renal disease, laboratory results and timeline dates were collected from the renal IT system. Timing of blood tests, renal progression, needing dialysis and patient survival were analysed. Reasons for discharge and cause of disease progression were reviewed in patients developing new estimated glomerular filtration rate <20 ml/min/1.73 m2. Patients were older (median age 75; interquartile range 63-84) with non-progressive, seemingly non-proteinuric renal disease. Median time to repeat blood test post-discharge was 75 days with 90% tested within 12 months. Sixty-six percent saw an improvement in kidney function post-discharge and only 13% had a decline of >10 ml/min/1.73 m2. Only 132 patients (6%) developed new advanced chronic kidney disease (estimated glomerular filtration rate < 20 ml/min/1.73 m2) of whom 40% were palliative, 36% had developed acute kidney injury and 23% discharged for failing to attend clinic. One hundred and thirty-four patients (6%) were referred back to nephrology and eight started dialysis of whom six were discharged for failure to attend clinic. Most discharged patients are low risk of progressive renal disease and need infrequent monitoring. Non-adherent patients discharged for failing to attend appear to be at risk of poor outcomes and new strategies are needed to better support this population.

Noninvasive Urinary Monitoring of Progression in IgA Nephropathy.

Standard methods for detecting and monitoring of IgA nephropathy (IgAN) have conventionally required kidney biopsies or suffer from poor sensitivity and specificity. The Kidney Injury Test (KIT) Assay of urinary biomarkers has previously been shown to distinguish between various kidney pathologies, including chronic kidney disease, nephrolithiasis, and transplant rejection. This validation study uses the KIT Assay to investigate the clinical utility of the non-invasive detection of IgAN and predicting the progression of renal damage over time. The study design benefits from longitudinally collected urine samples from an investigator-initiated, multicenter, prospective study, evaluating the efficacy of corticosteroids versus Rituximab for preventing progressive IgAN. A total of 131 urine samples were processed for this study; 64 urine samples were collected from 34 IgAN patients, and urine samples from 64 demographically matched healthy controls were also collected; multiple urinary biomarkers consisting of cell-free DNA, methylated cell-free DNA, DMAIMO, MAMIMO, total protein, clusterin, creatinine, and CXCL10 were measured by the microwell-based KIT Assay. An IgA risk score (KIT-IgA) was significantly higher in IgAN patients as compared to healthy control (87.76 vs. 14.03, p < 0.0001) and performed better than proteinuria in discriminating between the two groups. The KIT Assay biomarkers, measured on a spot random urine sample at study entry could distinguish patients likely to have progressive renal dysfunction a year later. These data support the pursuit of larger prospective studies to evaluate the predictive performance of the KIT-IgA score in both screening for non-invasive diagnosis of IgAN, and for predicting risk of progressive renal disease from IgA and utilizing the KIT score for potentially evaluating the efficacy of IgAN-targeted therapies.

Albuminuria in Pediatric Neurogenic Bladder: Identifying an Earlier Marker of Renal Disease

ObjectiveTo investigate the role of albuminuria as a clinical marker of early renal disease in children with neurogenic bladder (NGB) in association with commonly used predictors of renal risk. MethodsCatheterized urine was obtained from 40 patients with NGB at a tertiary pediatric hospital. Albumin-to-creatinine ratio (ACR) was analyzed for associations with estimated glomerular filtration rate, vesicoureteral reflux, hydronephrosis, bladder dynamics, and renal scarring. ResultsAbout 32% (13/40) of NGB patients had elevated ACR (≥30 mg/g. Elevated ACR was associated with Caucasian race, clean intermittent catheterization, hydronephrosis, and vesicoureteral reflux on univariate analysis. In multivariable analysis, presence of vesicoureteral reflux and use of anticholinergic medication were significant predictors of ACR elevation. ConclusionAlbuminuria is an established clinical predictor of renal disease and risk for progression to renal failure. The presence of albuminuria in NGB patients with urinary tract abnormalities suggests these patients may be at increased risk for progressive renal disease. This supports the clinical utility of adding ACR to the evaluation of renal risk in pediatric NGB.

Chronic kidney disease staging with cystatin C or creatinine-based formulas: flipping the coin.

Chronic kidney disease (CKD) affects 10-13% of the population worldwide. CKD classification stratifies patients in five stages of risk for progressive renal disease based on estimated glomerular filtration rate (eGFR) by formulas and albuminuria. However, the reliability of formulas to reflect real renal function is a matter of debate. The effect of the error of formulas in the CKD classification is unclear, particularly for cystatin C-based equations. We evaluated the reliability of a large number of cystatin C and/or creatinine-based formulas in the definition of the stages of CKD in 882 subjects with different clinical situations over a wide range of glomerular filtration rates (GFRs) (4.2-173.7 mL/min). Misclassification was a constant for all 61 formulas evaluated and averaged 50% for creatinine-based and 35% for cystatin C-based equations. Most of the cases were misclassified as one stage higher or lower. However, in 10% of the subjects, one stage was skipped and patients were classified two stages above or below their real stage. No clinically relevant improvement was observed with cystatin C-based formulas compared with those based on creatinine. The error in the classification of CKD stages by formulas was extremely common. Our study questions the reliability of both cystatin C and creatinine-based formulas to correctly classify CKD stages. Thus the correct classification of CKD stages based on estimated GFR is a matter of chance. This is a strong limitation in evaluating the severity of renal disease, the risk for progression and the evolution of renal dysfunction over time.

Prevalence of Microalbuminuria in Children with Asymptomatic Microscopic Hematuria

Introduction: A wide range of chronic and acute diseases begin with asymptomatic microscopic hematuria. Simultaneous presence of microalbuminuria and microscopic hematuria is suggestive of an important kidney disease. The purpose of this study was to determine the prevalence of microalbuminuria in children with asymptomatic microscopic hematuria. Materials and Methods : This cross-sectional study was done on 150 children aged 2-14 years with asymptomatic microscopic hematuria at Nephrology Clinic of Children’s Hospital Medical Center in 2013-2015. All patients had clinical and laboratory tests such as BUN, creatinine, electrolytes, urine albumin/ creatinine ratio, blood pressure, etc. The obtained data were recorded and analyzed with SPSS (ver. 18). All children with anatomical anomalies, hypertension, previous urinary tract surgery, or nephrolithiasis were excluded from the study. Results: The overall prevalence of microalbuminuria was 14.5 % and there was a significant relationship between microalbuminuria and the presence of dysmorphic red blood cells on urine analysis (p-value<0.05). The incidence of RBC cast was 54% (82 patients). Two children had upper-normal levels of blood pressure for age and sex that were followed closely and received special diets and medications. Twenty-nine patients (18.6%) had a positive family history of asymptomatic microscopic hematuria and the father of one of them had IgA nephropathy with ESRD. In children with microalbuminuria that received drugs for 3-28 months (mean, 6.3 months), microalbuminuria decreased significantly. Conclusions: Isolated asymptomatic microscopic hematuria is a benign disease but its association with proteinuria may indicate a serious problem with the risk of progressive renal disease. It is recommended to determine the microalbumin/creatinine ratio in cases with asymptomatic microscopic hematuria. Keywords : Asymptomatic Microscopic Hematuria; Microalbuminuria; Prevalence; Child.

Sex differences in vascular stiffness and relationship to the risk of renal functional decline in patients with type 2 diabetes

Recent data suggest that the higher risk of end-stage renal disease in women compared with men is associated with waist circumference. We investigated whether vascular stiffness which is linked to visceral fat accumulation is gender specific and associated with a loss in renal function. We studied 166 patients with type 2 diabetes at high risk of progressive renal disease. A vascular stiffness index was derived from measurement of the peripheral arterial pulse waveform using infrared finger photoplethysmography. Multiple regression analysis was used to examine the relationship between vascular stiffness and traditional clinical and biochemical renal disease risk factors. Women were of similar mean (standard deviation) age [61.6 (6.8) vs 60.0 (8.3) years; p = 0.444] and duration of diabetes [9.8 (7.2) vs 10.9 (8.1) years; p = 0.885] compared to men. Waist circumference was significantly associated with vascular stiffness [regression coefficient B = 0.15 (95% confidence interval: 0.06-2.24); p = 0.001]. There was a negative slope parameter for the relationship between glomerular filtration rate and vascular stiffness [ B = -0.15 (95% confidence interval: -0.22 to -0.09); p < 0.001] in women only. In this cohort, early renal functional decline in women is linked to increased vascular stiffness which may be associated with visceral fat accumulation as determined by waist circumference.

Modulation of endogenous antioxidant defense and the progression of kidney disease in multi-heritage groups of patients with type 2 diabetes: PRospective EValuation of Early Nephropathy and its Treatment (PREVENT).

BackgroundDiabetes is the western world’s leading cause of end-stage renal disease. Glucose-dependent, oxidative stress is linked to the development of renal inflammation and sclerosis, which, in animal models of diabetes, can be prevented by anti-oxidative treatment. Patients of non-Caucasian heritage have low activity of the selenoprotein, antioxidant enzyme, glutathione peroxidase (GPx) and its co-factor vitamin E, which may be linked to their increased propensity to developing end-stage renal disease.Research design and methodsWe have designed a double-blind, randomized, placebo controlled study with selenium and/or vitamin E versus placebo as the interventions for patients with type 2 diabetes and chronic kidney disease (CKD) stages 1–3. A 2 × 2 factorial design will allow a balanced representation of the heritage groups exposed to each intervention. The primary biochemical outcome is change in GPx activity, and clinical outcome measure is the actual, rate of—and/or percentage change in estimated glomerular filtration rate (eGFR) from baseline. Analysis will be with a marginal model for longitudinal data using Generalized Estimating Equations corrected for measures of baseline serum antioxidant enzyme activities (GPx, superoxide dismutase and catalase), micronutrient levels (vitamins E and C), measures of inflammation (interleukin 6, c-reactive protein and monocyte chemoattractant protein-1) and markers of oxidative damage (plasma 8-isoprostaglandin F2α and urinary 8-hydroxydeoxyguanosine).Expected resultsThe study will assess the relationship between GPx activity, oxidative stress, inflammation and eGFR. It will test the null hypothesis that antioxidant therapy does not influence the activity of GPx or other antioxidant enzymes and/or alter the rate of change in eGFR in these patient groups.ConclusionsOutcome data on the effect of antioxidants in human diabetic renal disease is limited. Previous post hoc analyses have not shown a beneficial effect of vitamin E on renal function. A recent trial of a pharmaceutical antioxidant agent, improved eGFR, but in patients with advanced diabetes-related chronic kidney disease its use was associated with an increased incidence of cardiovascular events. We will explore whether the nutritional antioxidants, vitamin E and selenium alone, or in combination in patients at high risk of renal disease progression, forestalls a reduction in eGFR. The study will describe whether endogenous antioxidant enzyme defenses can be safely modified by this intervention and how this is associated with changes in markers of oxidative stress.Trial registration ISRCTN 97358113. Registered 21st September 2009

High urinary sulfate concentration is associated with reduced risk of renal disease progression in type 2 diabetes

Diabetes is associated with a high incidence of microvascular disease, including nephropathy. Diabetic nephropathy is the most common cause of chronic kidney disease in the Western world. Sulfate in the urine is the metabolic end product of hydrogen sulfide (H2S), a recent discovered gaseous signaling molecule. Urinary sulfate has earlier shown beneficial predictive properties in renal transplant recipients. Based on the protective role of exogenous H2S in experimental models of diabetic nephropathy, we aimed to cross-sectionally investigate the association of sulfate with renal risk markers, and to prospectively investigate its predictive value for renal events in patients with diabetic nephropathy.Post-hoc analysis on data of the sulodexide macroalbuminuria (Sun-MACRO) trial and the Prevention of Renal and Vascular End-Stage Disease (PREVEND) study was performed. A total of 1004 patients with type 2 diabetes were included. Urinary sulfate concentration was measured and cross-sectionally associated to renal risk markers by linear regression. Multivariable Cox regression analysis was performed to assess the prospective association of sulfate with renal events, which was defined as end stage renal disease or a doubling of baseline serum creatinine.Mean age was 63 ± 9 years, median sulfate concentration was 8.0 (IQR 5.8–11.4) mmol/L. Urinary sulfate positively associated with male gender, hemoglobin, and negatively associated with albuminuria at baseline. During follow-up for 12 (IQR 6–18) months, 38 renal events occurred. Each doubling of urinary sulfate was associated with a 19% (95%CI 1%–34%) lower risk of renal events, independent of adjustment for potential confounders, including age, estimated glomerular filtration rate (eGFR), and albuminuria.To conclude, higher urinary sulfate concentration is associated with a more beneficial profile of renal risk markers, and is independently associated with a reduced risk for renal events in type 2 diabetes patients with nephropathy.

Effect of Urate Lowering Therapy on Renal Disease Progression in Hyperuricemic Patients with Chronic Kidney Disease.

To determine whether urate lowering therapy (ULT) could delay renal disease progression in hyperuricemic patients with chronic kidney disease (CKD). We performed a retrospective review of hyperuricemic patients with stage 3 CKD followed from September 2005 to July 2014 in Dongguk University Ilsan Hospital, Goyang, Korea. A total of 158 eligible patients were identified and 65 of them were treated with ULT in addition to the usual CKD management. We divided the patients according to the use of ULT and compared the estimated glomerular filtration rate (eGFR) change from baseline value and the proportion of renal disease progression (decline of eGFR > 30% of the baseline value, initiation of dialysis or eGFR < 15 ml/min/1.73m(2)) at the time of last followup. Risk factors for renal disease progression were identified by logistic regression analysis. After a median followup of 118.5 weeks (minimum 25, maximum 465), the ULT group showed better outcomes compared to the non-ULT group in terms of eGFR change from baseline (-1.19 ± 12.07 vs -7.37 ± 11.17 ml/min/1.73 m(2), p = 0.001) and the proportion of renal disease progression (12.3% vs 27.9%, p = 0.01). Goal-directed ULT showed better clinical outcomes compared to maintaining the initial ULT dose. Actual (area under the SUA-time curve adjusted by total observation time period) serum uric acid was significantly associated with the risk of renal disease progression (p for trend = 0.04) and actual serum uric acid level < 7 mg/dl reduced the risk of renal disease progression by 69.4%. ULT significantly delayed renal disease progression in hyperuricemic patients with CKD. Goal-directed ULT seems to be better than continuing the initial ULT prescription.