Predictor Of Renal Function Decline Research Articles

Reduced cortical oxygenation predicts a progressive decline of renal function in patients with chronic kidney disease

Renal tissue hypoxia is a final pathway in the development and progression of chronic kidney disease (CKD), but whether renal oxygenation predicts renal function decline in humans has not been proven. Therefore, we performed a prospective study and measured renal tissue oxygenation by blood oxygenation level-dependent magnetic resonance imaging (BOLD-MRI) in 112 patients with CKD, 47 with hypertension without CKD, and 24 healthy control individuals. Images were analyzed with the twelve-layer concentric objects method that divided the renal parenchyma in 12 layers of equal thickness and reports the mean R2* value of each layer (a high R2* corresponds to low oxygenation), along with the change in R2* between layers called the R2* slope. Serum creatinine values were collected to calculate the yearly change in estimated glomerular function rate (MDRD eGFR). Follow up was three years. The change in eGFR in CKD, hypertensive and control individuals was -2.0, 0.5 and -0.2 ml/min/1.73m2/year, respectively. In multivariable regression analysis adjusted for age, sex, diabetes, RAS-blockers, eGFR, and proteinuria the yearly eGFR change correlated negatively with baseline 24 hour proteinuria and the mean R2* value of the cortical layers, and positively with the R2* slope, but not with the other covariates. Patients with CKD and high outer R2* or a flat R2* slope were three times more likely to develop an adverse renal outcome (renal replacement therapy or over a 30% increase in serum creatinine). Thus, low cortical oxygenation is an independent predictor of renal function decline. This finding should stimulate studies exploring the therapeutic impact of improving renal oxygenation on renal disease progression.

Increased Arterial Stiffness is an Independent Predictor of Renal Function Decline in Patients With Type 2 Diabetes Mellitus Younger Than 60Years.

BackgroundThe objective of this study was to evaluate whether aortic pulse wave velocity (Ao‐PWV) predicts estimated glomerular filtration rate (eGFR) decline in patients with type 2 diabetes mellitus.Methods and ResultsThis prospective single‐center cohort study investigated 211 type 2 diabetes mellitus patients with eGFR ≥45 mL/min with a baseline mean age of 60.1 years (range, 30–82 years). The mean±SD baseline eGFR was 85±26.1 mL/min. We divided the cohort into 2 groups above (n=117, “older”) and below (n=94, “younger”) the mean age to evaluate whether Ao‐PWV predicted progression of kidney disease differentially in older and younger patients. The primary end point was reaching a final eGFR below the median for the age group and an eGFR fall ≥1 mL/min per year. Median follow‐up was 9 years (range, 3–11 years) and ≈50% of patients in both groups reached the primary end point. In older patients, Ao‐PWV was similar in those who did and did not reach the primary end point. By contrast, younger patients who reached the primary end point had a higher Ao‐PWV at baseline compared with those who did not (10.8 m/s versus 9.5 m/s, respectively; mean difference of 1.36 m/s [95% CI, 0.38–2.33], P=0.007). Ao‐PWV was an independent predictor of the primary end point (incident risk ratio, 1.09; 95% CI, 1.02–1.18) after adjustment for traditional risk factors only in younger patients (P=0.02). A 1m/s increase in Ao‐PWV was associated with a mean fall in eGFR of 2.1 mL/min per year (95% CI, 0.09–4.1) independent of other risk factors in younger patients (P=0.04).ConclusionsAo‐PWV predicts eGFR decline, before the onset of advanced renal dysfunction, and is a potential target for renoprotection in younger patients with type 2 diabetes mellitus.

GLUTATHIONE PEROXIDASE PRO200LEU GENE POLYMORPHISM AS A POTENTIAL PREDICTOR OF RENAL FUNCTION DECLINE IN RENAL TRANSPLANT RECIPIENTS

Mutations in genes encoding antioxidant enzymes may reduce their activity and make organism more prone to oxidative damage. The objective of this study was to determine the distribution of glutathione peroxidase 1 (GPX1) Pro200Leu gene poly-morphism in renal transplant recipients and healthy volunteers, as well as the association between investigated gene polymorphism and erythrocytes' antioxidative status and estimated GFR (eGFR) within a two-year follow-up after renal transplantation. A total of 85 patients with transplanted kidney and 110 healthy volunteers were genotyped for GPX1 Pro200Leu gene polymorphisms using the polymerase chain reaction - restriction fragment length polymorphism (PCR-RFLP) method. Of all patients enrolled in genotyping analysis, only 72 patients on tacrolimus went into oxidative stress parameters research. We measured the erythrocytes' concentration of reduced glutathione (GSH) and the activities of GPX and glutathione reductase (GR). GFR was estimated by MDRD formula for creatinine clearance. There was no statistical difference in the distribution of GPX1 gene polymorphism between patients and controls. The obtained results demonstrated that renal transplant recipients with Leu/Leu genotype of tested GPX1 polymorphism had higher erythrocytes' activity of GR compared to the carries of Pro/Pro genotype, but there were no differences in other oxidative stress parameters. The carriers of at least one Leu allele (Pro/Leu + Leu/Leu genotype) had significant decline in eGFR between the first and second year post-transplant. Genotyping of tested polymorphism in clinical practice may represent significant predictor of renal function decline and may provide identification of patients at high risk of graft loss.

Arterial stiffness and decline of renal function in a primary care population.

Arterial stiffness is an important pathophysiological factor linking cardiovascular disease and kidney disease. Controversy exists as to whether arterial stiffness causes renal function decline, or kidney dysfunction leads to stiffening or whether the association is mutual. We aimed to investigate the longitudinal association between arterial stiffness and annual rate of renal function decline. We prospectively investigated in a primary care population whether carotid-femoral pulse wave velocity (PWV) was associated with estimated glomerular filtration rate (eGFR) and annual decline in eGFR in participants aged ⩾40 years without overt kidney disease. Baseline data on PWV and eGFR were available for 587 participants; follow-up measurements with a mean duration of 5.6 years were available for 222 patients. PWV, female gender and mean arterial pressure were independently associated with eGFR at baseline, although age confounded this association. More importantly, baseline PWV, age and eGFR were independent predictors of renal function decline. Stratification for age showed that the effect of PWV on rate of eGFR decline was amplified with advancing age. On the other hand, baseline eGFR did not determine annual change in PWV, suggesting a unidirectional association between arterial stiffness and eGFR. Arterial stiffness amplifies age-related renal function decline, suggesting that arterial stiffness plays a causal role in the development of renal damage, at least at later stages of age-related renal function decline, possibly through impaired renal autoregulation and increased arterial blood pressure pulsatility.

Predictors of Renal Function Decline in Chinese Patients with Type 2 Diabetes Mellitus and in a Subgroup of Normoalbuminuria: A Retrospective Cohort Study.

Risk factors related to renal function decline in type 2 diabetes mellitus (T2DM) remain uncertain. This study aimed to investigate risk factors in relation to renal function decline in patients with T2DM and in a subgroup of patients with normoalbuminuria. This study was a retrospective cohort study, which included 451 patients with T2DM aged 63 ± 14 years admitted to a tertiary hospital in Beijing, China, between April and December 2010 and followed up for 6-60 months. Endpoint was renal function decline, defined as estimated glomerular filtration rate less than 60 mL/min 1.73 m2 or at least twofold increase of serum creatinine. Cox proportional hazards analysis was used to estimate hazard ratios (HRs) for candidate risk factors of renal function decline. After a median follow-up of 3.3 years, 94 (20.8%) patients developed renal function decline. Increased age (HR, 1.045; 95% CI, 1.020-1.070), albuminuria (HR, 1.956; 95%CI, 1.271-3.011), mild renal dysfunction (HR, 4.521; 95%CI, 2.734-7.476), hyperfiltration (HR, 3.897; 95%CI, 1.572-9.663), and increased hemoglobin A1c (HR, 1.128; 95%CI, 1.020-1.249) were identified as major risk factors. Among a subgroup of 344 patients with normoalbuminuria at baseline, 53 (15.4%) patients developed renal function decline. Increased age (HR, 1.089; 95%CI, 1.050-1.129), mild renal dysfunction (HR, 4.667; 95%CI, 2.391-9.107), hyperfiltration (HR, 5.677; 95%CI, 1.544-20.872), smoking (HR, 2.886; 95%CI, 1.370-6.082), higher pulse pressure (HR, 1.022; 95%CI, 1.004-1.040), and increased fasting glucose (HR, 1.104; 95%CI, 1.020-1.194) were major risk factors. Risk factors of diabetic renal impairment in T2DM should be screened and evaluated at an early stage of diabetes. Albuminuria, mild renal dysfunction, hyperfiltration, increased blood glucose, increased pulse pressure, and smoking were all predictors for diabetic renal impairment and interventions that focus on these risk factors may reduce further decline in renal function.

Impact of medication adherence on renal function in comorbid patients with type 2 diabetes and depression: protocol for a cohort study.

BackgroundPrevention, or slowing the progression, of diabetic nephropathy is one of the important goals in diabetes care. Although the impact of depression is a concern in patients with diabetes, it is unknown whether there is an association between adherence to hypoglycemic medication and the decline of renal function in comorbid patients with diabetes and depression. We will conduct a cohort study aimed at examining (1) depression as a predictor of renal function decline, and (2) how adherence to hypoglycemic medication relates to depression and renal function decline in patients with type 2 diabetes.Methods/DesignIn this multicenter cohort study, 550 patients with type 2 diabetes aged 20 years and older will be recruited at 20 outpatient clinics in general medicine and psychiatry. We will measure depression (Patient Health Questionnaire), medication adherence (medication possession ratio, Morisky Medication Adherence Scale, and one-item hypoglycemic medication adherence scale), and renal function (urinary albumin-creatinine ratio and estimated glomerular filtration rate) at baseline and at the 12-month follow-up. The primary endpoint is decline of renal function at 12 months. The secondary endpoints include clinical variables, quality of life, and the attitude of professionals toward depression. We will perform multivariable linear regression analysis to evaluate the effects of medication adherence on the decline of renal function in comorbid patients with type 2 diabetes and depression.DiscussionTo our knowledge, this will be the first study to examine how adherence to hypoglycemic medication relates to the decline of renal function in comorbid patients with type 2 diabetes and depression. The results of the study will have implications for practitioners of diabetes care, policy makers, and researchers for the prevention and treatment of diabetic nephropathy.Trial registrationUMIN000017513 (Registered on May 22, 2015)

The PR interval and QRS duration could be predictors of renal function decline

ObjectivePrevious studies have implicated PR interval (iPR) and QRS duration (dQRS) obtained by electrocardiography in independent predictors of cardiovascular disease, which often precedes renal dysfunction. The aim of this study was to examine whether iPR or dQRS could be a predictor of renal function decline in a community-based cohort. MethodsWe enrolled 1149 healthy subjects, and retrospectively evaluated the relationships between iPR or dQRS and renal function decline, observation period of which was 3 years, and assessed whether iPR or dQRS could predict renal function decline. ResultsThe iPR (r = −0.102, p = 0.0006) or dQRS (r = −0.097, p = 0.0010) was negatively associated with a rate of decline in estimated glomerular filtration rate (eGFR). Multiple regression analyses revealed that iPR (β = −0.095, p = 0.0023) or dQRS (β = −0.069, p = 0.0351) was an independent determinant of the rate of decline in eGFR after adjustment for covariates. Logistic regression analyses demonstrated that the longest iPR (odds ratios (OR), 2.03; 95% confidence intervals (CI), 1.49 to 2.76; p < 0.0001) or dQRS (OR, 1.62; 95% CI, 1.16 to 2.25; p = 0.0043) tertile showed an increased OR for prevalence of the rate of decline in eGFR ≤ 1 ml/min/1.73 m2/year compared to the shortest iPR or dQRS tertile after adjustment for covariates. ConclusionThe iPR and dQRS could be independent predictors of renal function decline in healthy subjects.

Simplicity is the ultimate sophistication. PR electrocardiographic intervals for smart forecasting of decline in renal function

Simplicity is the ultimate sophistication. PR electrocardiographic intervals for smart forecasting of decline in renal function

Preoperative predictors of renal function decline after radical nephroureterectomy for upper tract urothelial carcinoma

To model renal function after radical nephroureterectomy (RNU) for upper tract urothelial carcinoma (UTUC). To identify predictors of renal function decline after surgery, thereby allowing the identification of patients likely to be ineligible for cisplatin-based chemotherapy in the adjuvant setting. We retrospectively identified 374 patients treated with RNU for UTUC at three centres between 1995 and 2010. Estimated glomerular filtration rate (eGFR) was calculated using Chronic Kidney Disease Epidemiology Collaboration equation before RNU and at early (1-5 months after RNU) and late (>5 months) time points after RNU. Only patients deemed eligible for cisplatin-based chemotherapy before RNU (preoperative glomerular filtration rate [GFR] ≥60 mL/min/1.73 m(2) ) were included. Multivariable analysis identified the preoperative predictors of eGFR after RNU at early postoperative and late postoperative time points. A total of 163 patients had an eligible early post-RNU eGFR measurement and 172 had an eligible late eGFR measurement. The median eGFR declined by 32% and did not show a significant trend toward recovery over time (P = 0.4). On multivariable analysis preoperative eGFR and patient age were significantly associated with early and late postoperative eGFR, while Charlson comorbidity index score was significantly associated with late postoperative eGFR alone. In patients with normal preoperative eGFR (≥60 mL/min/1.73 m(2) ), renal function decreases by one-third after RNU and does not show evidence of recovery over time. Elderly patients and those with pre-RNU eGFR closer to 60 mL/min/1.73 m(2) (lower eGFR in the present cohort) are more likely to be ineligible for adjuvant cisplatin-based chemotherapy regimens because of renal function loss after RNU.

The Gly460Trp polymorphism of alpha-adducin gene as a predictor of renal function decline over 4 years of follow-up in an apparently healthy Chinese population

There were conflict data between alpha-adducin Gly460Trp genetic variant and changes of renal function. We conducted a prospective study to investigate the influence of alph-adducin Gly460Trp polymorphism on the quantitative changes of renal function. Of 1500 people screened, 112 non-diabetic normotensive elderly Chinese were recruited and received biochemistry examination at the baseline, at the second and fourth year follow-up. Serum creatinine and calculated renal parameter, using Modification of Diet in Renal Disease (MDRD) Study, were used to evaluate renal function and their progression. Genotyping was performed by polymerase chain reaction-restriction fragment length polymorphism. Age was 71.9 ± 3.7 years (range 60-81). Serum creatinine and MDRD glomerular filtration rate (GFR) were significantly worsened at the 2 and 4-year follow-up (all P < 0.001). The magnitude of 4-year decline of MDRD GFR was significantly higher in subjects carrying the a-adducin Gly460Trp G-allele than TT genotype (P = 0.045). The multivariate analyses showed that a-adducin Gly460Trp (P = 0.034), baseline MDRD GFR (P < 0.001), diastolic blood pressure (P = 0.021) and body weight (P = 0.022) could independently predict 4-year change of MDRD GFR. This longitudinal study showed that the aging process was associated with decline of renal function in the healthy elderly. The alpha-adducin Gly460Trp gene polymorphism might modulate these changes in the Chinese. Thisprovides further knowledge essential in the assessment of renal disease and determination of renal function in the older subjects.

Vasopressin-2 receptor antagonists in autosomal dominant polycystic kidney disease: from man to mouse and back

Autosomal dominant polycystic kidney disease (ADPKD) is the most frequent inherited nephropathy, with an estimated prevalence of 1:1000. The disease is characterized by the development of multiple cysts from all nephron segments leading to the enlargement of both kidneys and replacement of normal parenchyma (see [1]). Change in total kidney volume over time is the strongest predictor of renal function decline in ADPKD [2]. Glomerular filtration rate remains preserved up to the age of 40 years in most patients because glomerular hyperfiltration in functioning nephrons compensates for the ongoing loss of renal tissue, until end-stage renal failure ensues in >50% of patients, usually in their fifth decade. Mutations in the PKD1 gene account for ~85% of the affected families, whereas the remaining cases are caused by mutations in PKD2. PKD1 encodes polycystin-1, an integral membrane protein with a large extracellular domain that probably functions as a receptor and/or an adhesion molecule, whereas PKD2 encodes polycystin-2, a non-selective cation channel belonging to the family of transient receptor potential channels. The polycystins are located in the primary cilium and interact to form a mechanosensory complex that is involved in intracellular Ca 21 homeostasis and various signalling pathways. Disruption of the complex leads to cyst development and enlargement resulting from tubular cell proliferation and transepithelial fluid secretion. The progressive understanding of these pathways has led to spectacular advances in the prospective treatment for ADPKD, including the blockade of vasopressin 2 receptor (V2R) to decrease the intracellular level of 3#-5#-cyclic adenosine monophosphate (cAMP) in cyst-lining tubular cells [1]. Vasopressin and cAMP in ADPKD

Clinical and Histologic Predictors of Renal Function Decline After Laparoscopic Partial Nephrectomy

Clinical and surgical factors predict renal function decline after laparoscopic partial nephrectomy (LPN). Additional histopathologic predictors may be found in the specimen's nonneoplastic tissue but were not studied. This study investigated the significance of histologic findings in addition to other known predictors of renal function after LPN. Data of 150 patients who underwent LPN was analyzed. Renal function changes (median follow-up 15 months) were correlated with perioperative and histopathologic parameters. Three histopathologic features were evaluated and graded in the nonneoplastic parenchyma: Glomerulosclerosis, arteriosclerosis (AS), and interstitial fibrosis/tubular atrophy. Estimated GFR (eGFR) and percent decline on postoperative day 1 (POD1) and at the last follow-up were measured. Median eGFR percent decline at POD1 and last follow-up was -17 and -10, respectively (P<0.001). New-onset ≥stage III chronic kidney disease developed in only 7% of the patients. Three factors independently predicted POD1 eGFR decline: Artery and vein clamping vs artery only clamping (P=0.002), male sex (P=0.015), and larger tumor (P=0.02). Long-term loss of renal function was associated with POD1 eGFR decline (P=0.002) and the percentage of AS (P=0.01). The study limitations include a retrospective analysis leading to variability in the follow-up length and a small size cohort. LPN is associated with a favorable renal function outcome in most patients. Pathologic findings in the nonneoplastic tissue, in addition to clinical parameters, can be used to predict which patients are more likely to experience renal function impairment.

The A1166C polymorphism of angiotensin II Type 1 receptor as a predictor of renal function decline over 4 years follow-up in an apparently healthy Chinese population

The angiotensin II Type 1 receptor (AT1R) A1166C (rs5186) genez polymorphism is equivocally associated with the patients' susceptibility to chronic kidney disease or end-stage renal disease. We conducted a prospective study to investigate the influence of AT1R A1166C gene polymorphism on the quantitative changes of renal function. Of 1500 people screened, 112 non-diabetic normotensive elderly Chinese were recruited and received biochemistry examination at the baseline, at the second and fourth year follow-up. Serum creatinine and calculated renal parameters, using Cockroft-Gault (CG) formula, Modification of Diet in Renal Disease (MDRD) Study and abbreviated MDRD (abMDRD) equation, were used to evaluate renal function and their progression. Genotyping was performed by polymerase chain reaction-restriction fragment length polymorphism. Age was 71.9 +/- 3.7 years (range 60 - 81). Serum creatinine, CG creatinine clearance (CrCl), MDRD and abMDRD glomerular filtration rate (GFR) were significantly decreased at the 2 and 4-year follow-up (all p < 0.001). The magnitude of 4-year decline of above four renal parameters was significantly higher in subjects carrying the AT1R AA genotype than C-allele carriers (p = 0.014, 0.033, 0.008 and 0.014 for creatinine, CG CrCl, MDRD and abMDRD GFR, respectively). This association was still significant in multivariate analyses (p = 0.019, 0.045, 0.035 and 0.018, respectively). This longitudinal study showed that the aging process was associated with decline of renal function in the healthy elderly. The AT1R A1166C gene polymorphism might modulate these changes in the Chinese. This provides further knowledge essential in the assessment of renal disease and determination of renal function in the older subjects.

Kidney injury molecule‐1 in renal disease

Kidney injury molecule-1 (KIM-1) is a marker for renal proximal tubular damage, the hallmark of virtually all proteinuric, toxic and ischaemic kidney diseases. KIM-1 has gained increasing interest because of its possible pathophysiological role in modulating tubular damage and repair. In this respect, it is interesting that the best biomarkers often turn out to be important in modulation of damage and some even become therapeutic targets. The emphasis of this review is on structural and biochemical aspects of KIM-1, its expression pattern and its pathophysiological role in renal disease. We also discuss the prognostic impact of KIM-1 in relation to urinary protein excretion. Glomerular (proteinuria) and interstitial markers (KIM-1) might have independent prognostic impact and so may provide independent treatment targets. Finally, the potential of KIM-1 as biomarker of renal damage, as a predictor of renal function decline and its perspectives for monitoring therapy response, are discussed.

The D Allele of Angiotensin‐Converting Enzyme Polymorphism as a Predictor of Renal Function Decline over 4 Years in an Apparently Healthy Chinese Population Aged 60 and Older

To test the association between angiotensin-converting enzyme (ACE) insertion or deletion (I/D) polymorphism and decline of renal function in people aged 60 and older. Population-based prospective study with 4-year follow-up. Department of Internal Medicine and Family Medicine, Kaohsiung Medical University (KMU) Hospital and Graduate Institute of Medicine and Public Health, KMU. Of 1,500 people screened, 193 subjects were enrolled, and 144 completed 4 years of follow-up, 112 non-diabetic normotensive elderly people were analyzed. Subjects received biochemistry examination at baseline and at 2- and 4-year follow-ups. Serum creatinine and calculated renal parameters, including the Cockroft-Gault (CG) formula, the Jelliffe formula, and the Modification of Diet in Renal Disease (MDRD) Study equation, were used. Genetic polymorphism was analyzed according to the polymerase chain reaction. The mean age+/-standard deviation of the subjects was 71.9+/-3.7 (range 60-81). Serum creatinine, CG creatinine clearance (CrCl), Jelliffe CrCl, and MDRD glomerular filtration rate (GFR) were significantly lower at the 2- and 4-year follow-ups (all P < or = .001). At the 4-year follow-up, the magnitude of declines of the above four renal parameters was significantly higher in subjects with the ACE D allele than in the non-D-allele carriers (P = .01, .01, .04, and .01 for creatinine, CG CrCl, Jelliffe CrCl, and MDRD GFR, respectively). This association was still significant in multivariate analyses (P < or = .02 for all parameters). This longitudinal study showed the ACE I/D gene polymorphism might modulate renal function decline in elderly Chinese. This provides further knowledge essential in the assessment of renal disease and determination of renal function in older Chinese.