Acid retention accompanies reduced GFR in humans and increases plasma levels of endothelin and aldosterone

2011 ◽  
Vol 300 (4) ◽  
pp. F830-F837 ◽  
Author(s):  
Donald E. Wesson ◽  
Jan Simoni ◽  
Kristine Broglio ◽  
Simon Sheather
Keyword(s):  
Chronic Kidney Disease ◽  
Metabolic Acidosis ◽  
Plasma Levels ◽  
Filtration Rate ◽  
Mineralocorticoid Receptors ◽  
Acid Excretion ◽  
Vascular Effects ◽  
Estimated Gfr ◽  
Ckd Stage ◽  
Gfr Decline

Dietary alkali slows GFR decline in humans with a moderately reduced glomerular filtration rate (GFR) despite the absence of metabolic acidosis. Similarly, dietary alkali slows GFR decline in animals with 2/3 nephrectomy (Nx), a chronic kidney disease (CKD) model without metabolic acidosis in which GFR decline is mediated by acid (H+) retention through endothelin (ET) and mineralocorticoid receptors. To gain insight as to whether this mechanism might mediate GFR decline in humans, we explored whether macroalbuminuric subjects with moderately reduced (CKD stage 2 = 60–90 ml/min; CKD 2) compared with normal estimated GFR (>90 ml/min; CKD 1), each without metabolic acidosis, have H+ retention that increases plasma levels of ET-1 and aldosterone. Baseline plasma ET and aldosterone concentrations were each higher in CKD 2 than CKD 1. Baseline dietary H+ and urine net acid excretion (NAE) were not different between groups, but an acute oral NaHCO3 bolus reduced urine NAE less (i.e., postbolus urine NAE was higher) in CKD 2 than CKD 1, consistent with greater H+ retention in CKD 2 subjects. Thirty days of oral NaHCO3 reduced H+ retention in CKD 2 but not CKD 1 subjects and reduced plasma ET and aldosterone in both groups but to levels that remained higher in CKD 2 for each. Subjects with CKD stage 2 eGFR and no metabolic acidosis nevertheless have H+ retention that increases plasma ET and aldosterone levels, factors that might mediate subsequent GFR decline and other untoward vascular effects.

Observations from a teaching hospital in Ireland: changing from MDRD to CKD-EPI eGFR in routine practice

2020 ◽  
pp. jclinpath-2020-206713
Author(s):  
Janice Lee Veronica Reeve ◽  
Marion Davis ◽  
Patrick Joseph Twomey
Keyword(s):  
Chronic Kidney Disease ◽  
Kidney Disease ◽  
Filtration Rate ◽  
Clinical Chemistry ◽  
Routine Practice ◽  
Estimated Gfr ◽  
Ckd Stage ◽  
Service Application ◽  
Improved Accuracy ◽  
Older Males

Estimates of glomerular filtration rate (eGFR) help assess kidney function. Estimated GFR can be used to classify patients into one of six Chronic Kidney Disease (CKD) categories as recommended by the Kidney Disease Improving Global Outcomes clinical practice guidelines; CKD1 ≥90, CKD2 60–89, CKD3a 45–59, CKD3b 30–44, CKD4 15–29 or CKD5 ≤15 mL/min/1.73 m2. The Modification of Diet and Renal Disease (MDRD) study formula was widely adopted to calculate eGFR. The CKD Epidemiology Collaboration (CKD-EPI) formula improved accuracy of CKD staging at eGFR ≥60 mL/min/1.73 m2. MDRD and CKD-EPI eGFR were calculated on 111 444 serum creatinine results from adult patients measured as part of the routine Clinical Chemistry service. Application of CKD-EPI eGFR reclassified 18% to a lower (13.9%) or higher (4.0%) CKD stage. CKD staging was lower when <65 years and higher when ≥65 years. Females were more often reclassified compared with males (2.6% vs 0.8%). Overall, CKD-EPI eGFR classified less with CKD (stages 3a-5), unless ≥75 years. Older males and inpatients had higher CKD stages when CKD-EPI eGFR was applied. It has been recommended to replace MDRD eGFR with CKD-EPI eGFR. In general, doing this will have little impact, however, for some patients their CKD classification will be different.

scholarly journals Effect of Atorvastatin and Losartan on Glomerular Filtration Rate in Patients With Mild to Moderate Chronic Kidney Disease

KYAMC Journal ◽  
2019 ◽  
Vol 10 (1) ◽  
pp. 43-47
Author(s):  
Md Moniruzzaman Khan ◽  
Zesmin Fauzia Dewan ◽  
AKM Shahidur Rahman ◽  
Bakhtiare Md Shoeb Nomany ◽  
Ahmed Salam Mir ◽  
...  
Keyword(s):  
Chronic Kidney Disease ◽  
Glomerular Filtration Rate ◽  
Kidney Disease ◽  
Serum Creatinine ◽  
Glomerular Filtration ◽  
Filtration Rate ◽  
Kidney Diseases ◽  
Cell Damage ◽  
Renoprotective Effect ◽  
Ckd Stage

Background: Atorvastatin, a member of HMG CO-A reductase inhibitors, has been shown to have renoprotective effect in patients with Chronic Kidney Disease (CKD). Statins are supposed to decrease the oxidized lipid particles, suppress the activity of inflammatory mediators and prevent vascular thrombosis and thus could minimize renal cell damage. Losartan, an antihypertensive drug also diminishes proteinuria in patients with chronic kidney diseases or diabetes mellitus. Therefore the effect of concurrent use of atorvastatin and losartan on Glomerular Filtration Rate (GFR) could be a matter of interest from both Pharmacological and Clinical perspective. Objective: To assess the renoprotective effect of atorvastatin and losartan in patients with chronic kidney disease treated at Bangabandhu Sheikh Mujib Medical University (BSMMU). Materials and Method: Total forty four (44) patients suffering from CKD (stage one to stage three) were enrolled into two groups. Patients in Group A, received atorvastatin (10 mg) and losartan (50 mg) once daily for eight weeks. Patients in Group B, received losartan but not atorvastatin for the same duration. Serum creatinine level was measured at the commencement and also after eight weeks to calculate estimated glomerular filtration rate (eGFR) in individual patients with MDRD (Modification of Diet in Renal Disease) study equation. Results: There was significant (P < 0.001) reduction of Serum Creatinine and significant (P < 0.001) increase in e GFR in the patients, treated with atorvastatin and losartan. Conclusion: Concurrent administration of atorvastatin and losartan increased glomerular filtration rate (GFR) significantly in patients with chronic kidney disease. KYAMC Journal Vol. 10, No.-1, April 2019, Page 43-47

Early Glomerular Filtration Rate Loss as a Marker of Diabetic Nephropathy

2012 ◽  
Vol 08 (01) ◽  
pp. 40 ◽  
Author(s):  
George Jerums ◽  
Elif Ekinci ◽  
Sianna Panagiotopoulos ◽  
Richard J MacIsaac ◽  
◽  
...  
Keyword(s):  
Chronic Kidney Disease ◽  
Type 1 Diabetes ◽  
Diabetic Nephropathy ◽  
Glomerular Filtration Rate ◽  
Kidney Disease ◽  
Glomerular Filtration ◽  
Filtration Rate ◽  
Clinical Level ◽  
Ckd Stage

In the early 1980s, studies in type 1 diabetes suggested that glomerular filtration rate (GFR) loss begins with the onset of macroalbuminuria. However, recent evidence indicates that up to one-quarter of subjects with diabetes reach a GFR of less than 60 ml/min/1.73 m2(chronic kidney disease [CKD] stage 3) before developing micro- or macroalbuminuria. Furthermore, the prospective loss of GFR can be detected in early diabetic nephropathy (DN) well before CKD stage 3. Early GFR loss usually reflects DN in type 1 diabetes but, in older patients with type 2 diabetes, the assessment of early GFR loss needs to take into account the effects of aging. The assessment of GFR is now feasible at clinical level, using formulas based on serum creatinine, age, gender, and ethnicity. Overall, the estimation of early GFR loss is more accurate with the Chronic Kidney Disease Epidemiology (CKD–EPI) formula than with the Modification of Diet in Renal Disease (MDRD) study formula, but there is some evidence that the CKD-EPI formula does not exhibit better performance than the MDRD formula for estimating GFR in diabetes. Both formulas underestimate GFR in the hyperfiltration range. Formulas based on the reciprocal of cystatin C can also be used to estimate GFR, but their cost and lack of assay standardization have delayed their use at clinical level. In summary, early GFR loss is an important marker of DN as well as a potentially reversible target for interventions in DN.

scholarly journals Gambaran kadar ureum pada pasien penyakit ginjal kronik stadium 5 non dialisis

2016 ◽  
Vol 4 (2) ◽  
Author(s):  
Irendem K. A. Loho ◽  
Glady I. Rambert ◽  
Mayer F. Wowor
Keyword(s):  
Chronic Kidney Disease ◽  
Kidney Disease ◽  
Laboratory Tests ◽  
Filtration Rate ◽  
Descriptive Study ◽  
Clinical Syndrome ◽  
Blood Samples ◽  
Pathophysiological Process ◽  
Ckd Stage ◽  
Observational Descriptive Study

Abstract: Chronic kidney disease (CKD) is a pathophysiological process with diverse etiology, resulting in a progressive decreased in renal function, and generally ends up with kidney failure. In CKD patient, the level of urea increases -uremia- a clinical syndrome that occurs in all organs due to the increased level of urea. During catabolism process, protein is broken down into amino acids and deamination ammonia which is further synthesized to become urea. Increased level of urea depends on the glomerular filtration rate (GFR). Decreased of GFR (<15ml / min) can cause renal failure and uremia. This study aimed to determine the levels of urea in patients with stage 5 CKD non-dialysis. This was an observational descriptive study. This study was conducted from December 2015 to January 2016 at two hospitals, Prof. Dr. R. D. Kandou Hospital and Adventist Hospital Manado. Samples were blood samples of all patients suffering from CKD stage 5 non-dyalisis within the specified time. The results of laboratory tests showed that of 35 patients diagnosed with stage 5 CKD non-dialysis all had increased urea levels (100%). Conclusion: There was an increase in urea level of patients with stage 5 chronic kidney disease non-dialysis either of outpatients or inpatients.Keywords: urea serum, stage 5 non-dialysis chronic kidney disease.Abstrak: Penyakit ginjal kronik (PGK) merupakan suatu proses patofisiologi dengan etiologi beragam, mengakibatkan penurunan fungsi ginjal yang progresif dan umumnya berakhir dengan gagal ginjal. Umumnya pada PGK terjadi peningkatan kadar ureum dan mengakibat-kan terjadinya uremia yaitu suatu sindrom klinik yang terjadi pada semua organ akibat meningkatnya kadar ureum. Dalam proses katabolisme, protein dipecah menjadi asam amino dan deaminasi ammonia yang selanjutnya disintesis menjadi urea. Peningkatan kadar ureum bergantung pada tingkat laju filtrasi glomerulus (LFG). Pada penurunan LFG (<15ml/mnt) dapat terjadi gagal ginjal dan uremia. Penelitian ini bertujuan untuk mengetahui gambaran kadar ureum pada pasien penyakit ginjal kronik stadium 5 non-dialisis. Jenis penelitian ini ialah deskriptif observasional. Penelitian dilakukan sejak Desember 2015-Januari 2016 di RSUP Prof. Dr. R. D. Kandou dan RS Advent Teling Manado. Sampel penelitian ialah sampel darah dari semua pasien yang menderita penyakit ginjal kronik stadium 5 nondialisis dalam kurun waktu yang ditentukan. Hasil pemeriksaan laboratorium dari 35 pasien yang terdiagnosis penyakit ginjal kronik stadium 5 non dialisis memperlihatkan peningkatan kadar ureum serum (100%). Simpulan: Terjadi peningkatan kadar ureum serum pada pasien penyakit ginjal kronik stadium 5 non-dialisis baik yang dirawat jalan maupun dirawat inap.Kata kunci: ureum, penyakit ginjal kronik stadium 5 non dialisis

scholarly journals Urine citrate excretion identifies changes in acid retention as eGFR declines in patients with chronic kidney disease

2019 ◽  
Vol 317 (2) ◽  
pp. F502-F511 ◽  
Author(s):  
Nimrit Goraya ◽  
Jan Simoni ◽  
Lauren N. Sager ◽  
Abdullah Mamun ◽  
Nicolaos E. Madias ◽  
...  
Keyword(s):  
Chronic Kidney Disease ◽  
Metabolic Acidosis ◽  
Kidney Disease ◽  
Repeated Measures ◽  
Generalized Linear Model ◽  
Filtration Rate ◽  
Estimated Glomerular Filtration Rate ◽  
Urine Excretion ◽  
To Receive ◽  
Over Time

Previous studies have shown that acid (H+) retention in patients with chronic kidney disease (CKD) but without metabolic acidosis increases as the estimated glomerular filtration rate (eGFR) decreases over time. The present study examined whether changes in urine excretion of the pH-sensitive metabolite citrate predicted changes in H+ retention over time in similar patients with CKD that were followed for 10 yr. We randomized 120 CKD2 nondiabetic, hypertension-associated nephropathy patients with plasma total CO2 of >24 mM to receive 0.5 meq·kg body wt−1·day−1 NaHCO3 ([Formula: see text]; n = 40), 0.5 meq·kg body wt−1·day−1 NaCl (NaCl; n = 40), or usual care (UC; n = 40). We assessed eGFR (CKD-EPI) and H+ retention by comparing the observed with expected plasma total CO2 increase 2 h after an oral NaHCO3 bolus (0.5 meq/kg body wt). Although 10 yr versus baseline eGFR was lower for each group, 10-yr eGFR was higher ( P < 0.01) in [Formula: see text] (59.6 ± 4.8 ml·min−1·1.73 m−2) than NaCl and UC (52.1 ± 5.9 and 52.3 ± 4.1 ml·min−1·1.73 m−2, respectively) groups. Less eGFR preservation was associated with higher 10-yr versus baseline H+ retention in the NaCl group (26.5 ± 13.1 vs. 18.2 ± 15.3 mmol, P < 0.01) and UC group (24.8 ± 11.3 vs. 17.7 ± 10.9 mmol, P < 0.01) and with lower 10-yr versus baseline 8-h urine citrate excretion (UcitrateV) for the NaCl group (162 ± 47 vs. 196 ± 52 mg, respectively, P < 0.01) and UC group (153 ± 41 vs. 186 ± 42 mg, respectively, P < 0.01). Conversely, better eGFR preservation in the [Formula: see text] group was associated with no differences in 10-yr versus baseline H+ retention (14.2 ±13.5 vs. 16.1 ± 15.1 mmol, P = 1.00) or UcitrateV (212 ± 45 vs. 203 ± 49 mg, respectively, P = 0.74). An overall generalized linear model for repeated measures showed that UcitrateV predicted H+ retention ( P < 0.01). Less eGFR preservation in patients with CKD2 without metabolic acidosis was associated with increased H+ retention that was predicted by decreased UcitrateV.

scholarly journals Agreement and Precision Analyses of Various Estimated Glomerular Filtration Rate Formulae in Cancer Patients

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Wiwat Chancharoenthana ◽  
Salin Wattanatorn ◽  
Somratai Vadcharavivad ◽  
Somchai Eiam-Ong ◽  
Asada Leelahavanichkul
Keyword(s):  
Chronic Kidney Disease ◽  
Glomerular Filtration Rate ◽  
Glomerular Filtration ◽  
Cancer Patients ◽  
Filtration Rate ◽  
Estimated Glomerular Filtration Rate ◽  
Estimated Gfr ◽  
Anti Cancer ◽  
Precision And Accuracy ◽  
Racial Factor

AbstractThe accuracy of the estimated glomerular filtration rate (eGFR) in cancer patients is very important for dose adjustments of anti-malignancy drugs to reduce toxicities and enhance therapeutic outcomes. Therefore, the performance of eGFR equations, including their bias, precision, and accuracy, was explored in patients with varying stages of chronic kidney disease (CKD) who needed anti-cancer drugs. The reference glomerular filtration rate (GFR) was assessed by the 99mTc-diethylene triamine penta-acetic acid (99mTc-DTPA) plasma clearance method in 320 patients and compared with the GFRs estimated by i) the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation, ii) the unadjusted for body surface area (BSA) CKD-EPI equation, iii) the re-expressed Modification of Diet in Renal Disease (MDRD) study equation with the Thai racial factor, iv) the Thai eGFR equation, developed in CKD patients, v) the 2012 CKD-EPI creatinine-cystatin C, vi) the Cockcroft-Gault formula, and vii) the Janowitz and Williams equations for cancer patients. The mean reference GFR was 60.5 ± 33.4 mL/min/1.73 m2. The bias (mean error) values for the estimated GFR from the CKD-EPI equation, BSA-unadjusted CKD-EPI equation, re-expressed MDRD study equation with the Thai racial factor, and Thai eGFR, 2012 CKD-EPI creatinine-cystatin-C, Cockcroft-Gault, and Janowitz and Williams equations were −2.68, 1.06, −7.70, −8.73, 13.37, 1.43, and 2.03 mL/min, respectively, the precision (standard deviation of bias) values were 6.89, 6.07, 14.02, 11.54, 20.85, 10.58, and 8.74 mL/min, respectively, and the accuracy (root-mean square error) values were 7.38, 6.15, 15.97, 14.16, 24.74, 10.66, and 8.96 mL/min, respectively. In conclusion, the estimated GFR from the BSA-unadjusted CKD-EPI equation demonstrated the least bias along with the highest precision and accuracy. Further studies on the outcomes of anti-cancer drug dose adjustments using this equation versus the current standard equation will be valuable.

Impaired Tubular Secretion of Organic Solutes in Advanced CKD

2021 ◽  
pp. ASN.2021030336
Author(s):  
Robert Mair ◽  
Seolhyun Lee ◽  
Natalie Plummer ◽  
Tammy Sirich ◽  
Timothy Meyer
Keyword(s):  
Chronic Kidney Disease ◽  
Filtration Rate ◽  
Tubular Secretion ◽  
Indoxyl Sulfate ◽  
Organic Solutes ◽  
Plasma Samples ◽  
Considerable Variability ◽  
Metabolomic Analysis ◽  
Estimated Gfr ◽  
Fractional Clearance

Background The clearance of solutes removed by tubular secretion may be altered out of proportion to the glomerular filtration rate (GFR) in chronic kidney disease (CKD). Recent studies have described considerable variability in the secretory clearance of waste solutes relative to the GFR in patients with CKD. Methods To test the hypothesis that secretory clearance relative to GFR is reduced in patients approaching dialysis, we used metabolomic analysis to identify solutes in simultaneous urine and plasma samples from 16 CKD patients with an estimated GFR of 7±2 ml/min per 1.73m2 and 16 control participants. Fractional clearances were calculated as the ratios of urine to plasma levels of each solute relative to those of creatinine and urea in CKD patients and to those of creatinine in controls. Results Metabolomic analysis identified 39 secreted solutes with fractional clearance >3.0 in control participants. Fractional clearance values in CKD patients were reduced on average to 65%±27% of those in controls. These values were significantly lower for 18 of 39 individual solutes and significantly higher for only one. Assays of the secreted anions phenylacetyl glutamine, p-cresol sulfate, indoxyl sulfate, and hippurate confirmed variable impairment of secretory clearances in advanced CKD. Fractional clearances were markedly reduced for phenylacetylglutamine (4.2±0.6 for controls versus 2.3±0.6 for CKD patients, P<0.001), p-cresol sulfate (8.6±2.6 for controls versus 4.1±1.5 for CKD patients, P<0.001), and indoxyl sulfate (23.0±7.3 versus 7.5±2.8, P<0.001), but not for hippurate (10.2±3.8 versus 8.4±2.6, P=0.13). Conclusions Secretory clearances for many solutes are reduced more relative to the reduction in GFR in advanced CKD. Impaired secretion of these solutes might contribute to uremic symptoms as patients approach dialysis.

On the Basis of Race: The Utility of a Race Factor in Estimating Glomerular Filtration

2020 ◽  
Author(s):  
Caroline E Franks ◽  
Mitchell G Scott
Keyword(s):  
Chronic Kidney Disease ◽  
Glomerular Filtration Rate ◽  
Glomerular Filtration ◽  
Gold Standard ◽  
Filtration Rate ◽  
Routine Clinical Practice ◽  
Kidney Dysfunction ◽  
Estimated Gfr ◽  
Gold Standard Method ◽  
Estimation Equations

Abstract Background Glomerular filtration rate (GFR) is a measure of the combined rate of filtration of all functional nephrons in the kidney. Measurement of GFR is used in the clinic to detect, stratify, and monitor progression of kidney dysfunction, and also serves as a prognostic tool for staging chronic kidney disease (CKD). The gold standard method for measuring GFR is by plasma or urine clearance of exogenous filtration markers, but this is not feasible in routine clinical practice. The most commonly used method to assess GFR is using equations for estimated GFR (eGFR). Content Addition of a race factor to eGFR equations has been recommended to optimize performance for Black individuals. Here, we review the basis of the race-based equation and assess its utility and widespread applicability. Summary Although evidence supporting the performance of a race factor exists in the unique populations in which these estimation equations were derived, more studies are needed to assess the need, or lack thereof, for race factors for all ethnicities. Furthermore, ethnicity is complex and likely cannot be qualified with a 2-level descriptor.

Performance of creatinine-based equations for estimating glomerular filtration rate changes over time

2018 ◽  
Vol 35 (5) ◽  
pp. 819-827 ◽  
Author(s):  
Marieke H C van Rijn ◽  
Marie Metzger ◽  
Martin Flamant ◽  
Pascal Houillier ◽  
Jean-Philippe Haymann ◽  
...  
Keyword(s):  
Chronic Kidney Disease ◽  
Glomerular Filtration Rate ◽  
Kidney Disease ◽  
Glomerular Filtration ◽  
Filtration Rate ◽  
Patient Characteristics ◽  
Estimated Gfr ◽  
Changes Over Time ◽  
Over Time ◽  
Measured Gfr

Abstract Background Glomerular filtration rate (GFR) is commonly used to monitor chronic kidney disease (CKD) progression, but its validity for evaluating kidney function changes over time has not been comprehensively evaluated. We assessed the performance of creatinine-based equations for estimating GFR slope according to patient characteristics and specific CKD diagnosis. Methods In the NephroTest cohort study, we measured GFR 5324 times by chromium 51–labeled ethylenediamine tetraacetic acid renal clearance in 1955 adult patients with CKD Stages 1–4 referred to nephrologists (Stages 1–2, 19%) and simultaneously estimated GFR with both the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) and Modification of Diet in Renal Disease (MDRD) equations for isotope dilution mass spectrometry traceable creatinine; absolute and relative GFR slopes were calculated using a linear mixed model. Results Over a median follow-up of 3.4 [interquartile range (IQR) 2.0–5.6] years, the decline in mean absolute and relative measured GFR (mGFR) and CKD-EPI and MDRD estimated GFR (eGFR) was 1.6 ± 1.2, 1.5 ± 1.4 and 1.3 ± 1.3 mL/min/1.73 m2/year and 5.9 ± 5.3, 5.3 ± 5.3 and 4.8 ± 5.2%/year, respectively; 52% and 55% of the patients had MDRD and CKD-EPI eGFR slopes within 30% of mGFR slopes. Both equations tended to overestimate the GFR slope in the youngest patients and underestimate it in the oldest, thus producing inverse associations between age and mGFR versus eGFR slope. Other patient characteristics and specific CKD diagnoses had little effect on the performance of the equations in estimating associations. Conclusions This study shows little bias, but poor precision in GFR slope estimation for both MDRD and CKD-EPI equations. Importantly, bias strongly varied with age, possibly due to variations in muscle mass over time, with implications for clinical care and research.

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