Limited Value of Cystatin-C over Estimated Glomerular Filtration Rate for Heart Failure Risk Stratification

Background: to compare the prognostic value of estimated glomerular filtration rate, cystatin-C, an alternative renal biomarker, and their combination, in an outpatient population with heart failure.Estimated glomerular filtration rate is routinely used to assess renal function in heart failure patients. We recently demonstrated that the Cockroft-Gault formula is the best among the most commonly used estimated glomerular filtration rate formulas for predicting heart failure prognosis.Methodology: a total of 879 consecutive patients (72% men, age 70.4 years [P25-75 60.5-77.2]) were studied. The etiology of heart failure was mainly ischemic heart disease (52.7%). The left ventricular ejection fraction was 34% (P25-75 26-43%). Most patients were New York Heart Association class II (65.8%) or III (25.9%). During a median follow-up of 3.46 years (P25-75 1.85-5.05), 312 deaths were recorded. In an adjusted model, estimated glomerular filtration rate and cystatin-C showed similar prognostic value according to the area under the curve (0.763 and 0.765, respectively). In Cox regression, the multivariable analysis hazard ratios were 0.99 (95% CI: 0.98-1, P = 0.006) and 1.14 (95% CI: 1.02-1.28, P = 0.02) for estimated glomerular filtration rate and cystatin-C, respectively. Reclassification, assessed by the integration discrimination improvement and the net reclassification improvement indices, was poorer with cystatin-C (−0.5 [−1.0;−0.1], P = 0.024 and −4.9 [−8.8;−1.0], P = 0.013, respectively). The value of cystatin-C over estimated glomerular filtration rate for risk-stratification only emerged in patients with moderate renal dysfunction (eGFR 30-60 ml/min/1.73 m2, chi-square 12.9, P<0.001). Conclusions: taken together, the results indicate that estimated glomerular filtration rate and cystatin-C have similar long-term predictive values in a real-life ambulatory heart failure population. Cystatin-C seems to offer improved prognostication in heart failure patients with moderate renal dysfunction

Assessment of the Nova StatSensor whole blood point-of-care creatinine analyser for the measurement of kidney function in screening for chronic kidney disease

Point-of-care testing for creatinine using a fingerprick sample and resultant estimated glomerular filtration rate has potential for screening for chronic kidney disease in community settings. This study assessed the applicability of the Nova StatSensor creatinine analyzer for this purpose. Fingerprick samples from 100 patients (63 renal, 37 healthy volunteers; range 46–962 mmol/L) were assayed using two StatSensor analyzers. Lithium heparin venous plasma samples collected simultaneously were assayed in duplicate using the isotope dilution mass spectrometryaligned Roche Creatinine Plus enzymatic assay on a Hitachi Modular P unit. Method comparison statistics and the ability of the StatSensor to correctly categorise estimated glomerular filtration rate above or below 60 mL/min were calculated pre- and post-alignment with the laboratory method. Isotope dilution mass spectrometry alignment of the StatSensor will identify most patients with estimated glomerular filtration rate -60 mL/min, but there will be many falsely low estimated glomerular filtration rate results that require laboratory validation. Creatinine results need improvement

PENGARUH SUPLEMENTASI KAPSUL EKSTRAK IKAN GABUS TERHADAP LAJU FILTRASI GLOMERULUS PADA SINDROM NEFROTIK RESISTEN STEROID ANAK

Background Steroid Resistant Nephrotic Syndrome (SRNS) is one of nephrotic syndrome classification which do not respond to therapy with steroid. Children with SRNS have high risk of decline of kidney’s function. Glomerular filtration rate can be used as indicator of kidney’s function. Snakehead fish extract supplementation can increase serum albumin level, therefore is expected to increase glomerular filtration rate indirectly. Aim This study aims to prove the effect of Snakehead fish extract supplementation on glomerular filtration rate in children with SRNS aged 2-18 years old. Methods This was a quasi experimental study with pre and post design performed in the pediatric polyclinic of Kariadi General Hospital, Semarang. There were 10 patients which 3 of them drop out in the process. Patients recieved gabus-fish extract suplementation with 2x500 mg dose for 21 days. Data was statistically analyzed by paired t-test. Results The initial Glomerular filtration rate mean was 114,09 ± 41,60 ml/min/1,73 m2 decreased to 105,97 ± 33,81 ml/menit/1,73 m2 after the intervention, with differences mean of -8,12 ± 39,23 ml/menit/1,73 m2. There was no significant difference (p=0,604) in glomerular filtration rates before and after intervention. Conclusion Snakehead fish extract capsules supplementation at a dose of 2x500 mg for 21 days did not significantly change glomerular filtration rates of children with SRNS. Keywords Snakehead fish extract capsules, glomerular filtration rate, steroid resistant nephrotic syndrom

Assessment of glomerular filtration rate

Glomerular filtration rate (GFR) determination is the most frequently used laboratorial test to evaluate renal function. Indirect markers as blood determination of creatinine and cystatin C are used with this purpose, as well as the direct determination of GFR, with indicators like inulin; iodated contrasts, radioactive or not; and others. Serum creatinine is the test that is most commonly performed in order to evaluate GFR in the clinical pathology laboratory. However, in some conditions, aiming at the adequate interpretation of the test, the result of serum creatinine must be corrected (by using formulas that include individual characteristics of the subjects). In fact, inulin is still seen as the ideal marker of glomerular filtration, but its use is not directed to clinical practice; then the search for appropriate tests for routine use continues.A medida do ritmo de filtração glomerular (RFG) é a prova laboratorial mais utilizada na avaliação da função renal. Para tanto, usam-se marcadores indiretos, como as determinações de creatinina e cistatina C no sangue, ou procede-se à determinação do RFG propriamente dito, com indicadores como inulina; contrastes iodados, marcados ou não; e outras substâncias. O exame mais solicitado para avaliação do RFG no laboratório de patologia clínica é a dosagem da creatinina sérica. Em algumas condições, entretanto, o resultado encontrado da creatinina sérica deve ser corrigido (através da utilização de fórmulas que levam em consideração características próprias do indivíduo) para ser devidamente interpretado. De fato, a inulina ainda é vista como marcador ideal de filtração glomerular, mas seu uso não se destina à prática clínica, de modo que ainda hoje persiste a busca por testes adequados para uso rotineiro.Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)Universidade Federal de São Paulo (UNIFESP) Escola Paulista de Medicina da Universidade Federal de São Paulo (UNIFESP) Ambulatório de Glomerulopatias da Disciplina de NefrologiaUNIFESP, EPM, da UNIFESP, Ambulatório de Glomerulopatias da Disciplina de NefrologiaSciEL

Effect of Blood Pressure Control on Long-Term Risk of End-Stage Renal Disease and Death Among Subgroups of Patients With Chronic&nbsp;Kidney Disease.

Background Our objective was to explore the effect of intensive blood pressure (BP) control on kidney and death outcomes among subgroups of patients with chronic kidney disease divided by baseline proteinuria, glomerular filtration rate, age, and body mass index. Methods and Results We included 840 MDRD (Modification of Diet in Renal Disease) trial and 1067 AASK (African American Study of Kidney Disease and Hypertension) participants. We used Cox models to examine whether the association between intensive BP control and risk of end-stage renal disease (ESRD) or death is modified by baseline proteinuria (≥0.44 versus &lt;0.44&nbsp;g/g), glomerular filtration rate (≥30 versus &lt;30&nbsp;mL/min per 1.73&nbsp;m2), age (≥40 versus &lt;40&nbsp;years), or body mass index (≥30 versus &lt;30&nbsp;kg/m2). The median follow-up was 14.9&nbsp;years. Strict (versus usual) BP control was protective against ESRD (hazard ratio [HR]ESRD, 0.77; 95% CI, 0.64-0.92) among those with proteinuria ≥0.44&nbsp;g/g but not proteinuria &lt;0.44&nbsp;g/g. Strict (versus usual) BP control was protective against death (HRdeath, 0.73; 95% CI, 0.59-0.92) among those with glomerular filtration rate &lt;30&nbsp;mL/min per 1.73&nbsp;m2 but not glomerular filtration rate ≥30&nbsp;mL/min per 1.73&nbsp;m2 (HRdeath, 0.98; 95% CI, 0.84-1.15). Strict (versus usual) BP control was protective against ESRD among those ≥40&nbsp;years (HRESRD, 0.82; 95% CI, 0.71-0.94) but not &lt;40&nbsp;years. Strict (versus usual) BP control was also protective against ESRD among those with body mass index ≥30&nbsp;kg/m2 (HRESRD, 0.75; 95% CI, 0.61-0.92) but not body mass index &lt;30&nbsp;kg/m2. Conclusions The ESRD and all-cause mortality benefits of intensive BP lowering may not be uniform across all subgroups of patients with chronic kidney disease. But intensive BP lowering was not associated with increased risk of ESRD or death among any subgroups that we examined

Relationship between Estimated Glomerular Filtration Rate (eGFR) and Metabolic Syndrome in Japanese

We investigated the link between renal function as evaluated by estimated glomerular filtration rate (eGFR) and metabolic syndrome in Japanese. A total of 11,711 Japanese subjects, aged 20-79 years, were recruited in a cross-sectional clinical investigation. From this group, we further investigated the data on 1,576 subjects. eGFR was calculated using serum creatinine (Cr), age and sex. The diagnosis of metabolic syndrome was based on the Japanese criteria. In the first analysis, 288 men (7.8%) and 498 women (6.2%) were diagnosed with reduced eGFR (<60ml/min). eGFR was not correlated with anthropometric, body composition parameters in either sex. In the second analysis, in subjects without medications, 132 men (20.8%) and 15 women (1.6%) were diagnosed with metabolic syndrome. eGFR was lower in men with abdominal obesity and in women with hypertension was than in those without. Among Japanese not taking medications, lower eGFR may be a characteristic of men with abdominal obesity and of women with hypertension

Postnatal maturation of the glomerular filtration rate in conventional growing piglets as potential juvenile animal model for preclinical pharmaceutical research

Adequate animal models are required to study the preclinical pharmacokinetics (PK), pharmacodynamics (PD) and safety of drugs in the pediatric subpopulation. Over the years, pigs were presented as a potential animal model, since they display a high degree of anatomical and physiological similarities with humans. To assess the suitability of piglets as a preclinical animal model for children, the ontogeny and maturation processes of several organ systems have to be unraveled and compared between both species. The kidneys play a pivotal role in the PK and PD of various drugs, therefore, the glomerular filtration rate (GFR) measured as clearance of endogenous creatinine (Jaffe and enzymatic assay) and exo-iohexol was determined in conventional piglets aging 8 days (n = 16), 4 weeks (n = 8) and 7 weeks (n = 16). The GFR data were normalized to bodyweight (BW), body surface area (BSA) and kidney weight (KW). Normalization to BSA and KW showed an increase in GFR from 46.57 to 100.92 mL/min/m2 and 0.49 to 1.51 mL/min/g KW from 8 days to 7 weeks of age, respectively. Normalization to BW showed a less pronounced increase from 3.55 to 4.31 mL/min/kg. The postnatal development of the GFR was comparable with humans, rendering the piglet a convenient juvenile animal model for studying the PK, PD and safety of drugs in the pediatric subpopulation. Moreover, to facilitate the assessment of the GFR in growing piglets in subsequent studies, a formula was elaborated to estimate the GFR based on plasma creatinine and BW, namely eGFR =1.879 × BW^1.092/Pcr^0.600

Comparing Results of Five Glomerular Filtration Rate-Estimating Equations in the Korean General Population. MDRD Study, Revised Lund-Malmö, and Three CKD-EPI Equations

Estimated glomerular filtration rate (eGFR) is a widely used index of kidney function. Recently, new formulas such as the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equations or the Lund-Malmö equation were introduced for assessing eGFR. We compared them with the Modification of Diet in Renal Disease (MDRD) Study equation in the Korean adult population. METHODS: The study population comprised 1,482 individuals (median age 51 [42-59] yr, 48.9% males) who received annual physical check-ups during the year 2014. Serum creatinine (Cr) and cystatin C (CysC) were measured. We conducted a retrospective analysis using five GFR estimating equations (MDRD Study, revised Lund-Malmö, and Cr and/or CysC-based CKD-EPI equations). Reduced GFR was defined as eGFR &lt;60 mL/min/1.73 m². RESULTS: For the GFR category distribution, large discrepancies were observed depending on the equation used; category G1 (≥90 mL/min/1.73 m²) ranged from 7.4-81.8%. Compared with the MDRD Study equation, the other four equations overestimated GFR, and CysC-based equations showed a greater difference (-31.3 for CKD-EPI(CysC) and -20.5 for CKD-EPI(Cr-CysC)). CysC-based equations decreased the prevalence of reduced GFR by one third (9.4% in the MDRD Study and 2.4% in CKD-EPI(CysC)). CONCLUSIONS: Our data shows that there are remarkable differences in eGFR assessment in the Korean population depending on the equation used, especially in normal or mildly decreased categories. Further prospective studies are necessary in various clinical settings

Use of Estimating Equations for Dosing Antimicrobials in Patients with Acute Kidney Injury Not Receiving Renal Replacement Therapy.

Acute kidney injury (AKI) can potentially lead to the accumulation of antimicrobial drugs with significant renal clearance. Drug dosing adjustments are commonly made using the Cockcroft-Gault estimate of creatinine clearance (CLcr). The Modified Jelliffe equation is significantly better at estimating kidney function than the Cockcroft-Gault equation in the setting of AKI. The objective of this study is to assess the degree of antimicrobial dosing discordance using different glomerular filtration rate (GFR) estimating equations. This is a retrospective evaluation of antimicrobial dosing using different estimating equations for kidney function in AKI and comparison to Cockcroft-Gault estimation as a reference. Considering the Cockcroft-Gault estimate as the criterion standard, antimicrobials were appropriately adjusted at most 80.7% of the time. On average, kidney function changed by 30 mL/min over the course of an AKI episode. The median clearance at the peak serum creatinine was 27.4 (9.3⁻66.3) mL/min for Cockcroft Gault, 19.8 (9.8⁻47.0) mL/min/1.73 m² for MDRD and 20.5 (4.9⁻49.6) mL/min for the Modified Jelliffe equations. The discordance rate for antimicrobial dosing ranged from a minimum of 8.6% to a maximum of 16.4%. In the event of discordance, the dose administered was supra-therapeutic 100% of the time using the Modified Jelliffe equation. Use of estimating equations other than the Cockcroft Gault equation may significantly alter dosing of antimicrobials in AKI