Estimating Kidney Function in HIV-Infected Adults in Kenya: Comparison to a Direct Measure of Glomerular Filtration Rate by Iohexol Clearance

Background

More than two-thirds of the world''s HIV-positive individuals live in sub-Saharan Africa, where genetic susceptibility to kidney disease is high and resources for kidney disease screening and antiretroviral therapy (ART) toxicity monitoring are limited. Equations to estimate glomerular filtration rate (GFR) from serum creatinine were derived in Western populations and may be less accurate in this population.

Methods

We compared results from published GFR estimating equations with a direct measure of GFR by iohexol clearance in 99 HIV-infected, ART-naïve Kenyan adults. Iohexol concentration was measured from dried blood spots on filter paper. The bias ratio (mean of the ratio of estimated to measured GFR) and accuracy (percentage of estimates within 30% of the measured GFR) were calculated.

Results

The median age was 35 years, and 60% were women. The majority had asymptomatic HIV, with median CD4+ cell count of 355 cells/mm³. Median measured GFR was 115 mL/min/1.73 m². Overall accuracy was highest for the Chronic Kidney Disease Epidemiology Consortium (CKD-EPI) equation. Consistent with a prior report, bias and accuracy were improved by eliminating the coefficient for black race (85% of estimates within 30% of measured GFR). Accuracy of all equations was poor in participants with GFR 60–90 mL/min/1.73 m² (<65% of estimates within 30% of measured GFR), although this subgroup was too small to reach definitive conclusions.

Conclusions

Overall accuracy was highest for the CKD-EPI equation. Eliminating the coefficient for race further improved performance. Future studies are needed to determine the most accurate GFR estimate for use in individuals with GFR <90 mL/min/1.73 m², in whom accurate estimation of kidney function is important to guide drug dosing. Direct measurement of GFR by iohexol clearance using a filter paper based assay is feasible for research purposes in resource-limited settings, and could be used to develop more accurate GFR estimates in African populations.     

Fluid transport and cystogenesis in autosomal dominant polycystic kidney disease

Autosomal dominant polycystic kidney disease (ADPKD) is the most frequent inherited nephropathy. The development and enlargement of cysts in ADPKD requires tubular cell proliferation, abnormalities in the extracellular matrix and transepithelial fluid secretion. Multiple studies have suggested that fluid secretion across ADPKD cyst-lining cells is driven by the transepithelial secretion of chloride, mediated by the apical CFTR channel and specific basolateral transporters. The whole secretory process is stimulated by increased levels of cAMP in the cells, probably reflecting modifications in the intracellular calcium homeostasis and abnormal stimulation of the vasopressin V2 receptor. This review will focus on the pathophysiology of fluid secretion in ADPKD cysts, starting with classic, morphological and physiological studies that were followed by investigations of the molecular mechanisms involved and therapeutic trials targeting these pathways in cellular and animal models and ADPKD patients. This article is part of a Special Issue entitled: Polycystic Kidney Disease.     

Fibrosis and progression of Autosomal Dominant Polycystic Kidney Disease (ADPKD)

The age on onset of decline in renal function and end-stage renal disease (ESRD) in autosomal polycystic kidney disease (ADPKD) is highly variable and there are currently no prognostic tools to identify patients who will progress rapidly to ESRD. In ADPKD, expansion of cysts and loss of renal function are associated with progressive fibrosis. Similar to the correlation between tubulointerstitial fibrosis and progression of chronic kidney disease (CKD), in ADPKD, fibrosis has been identified as the most significant manifestation associated with an increased rate of progression to ESRD. Fibrosis in CKD has been studied extensively. In contrast, little is known about the mechanisms underlying progressive scarring in ADPKD although some commonality may be anticipated. Current data suggest that fibrosis associated with ADPKD shares at least some of the “classical” features of fibrosis in CKD (increased interstitial collagens, changes in matrix metalloproteinases (MMPs), over-expression of tissue inhibitor of metalloproteinase-1 (TIMP-1), over-expression of plasminogen activator inhibitor-1 (PAI-1) and increased transforming growth factor beta (TGFβ) but that there are also some unique and stage-specific features. Epithelial changes appear to precede and to drive interstitial changes leading to the proposal that development of fibrosis in ADPKD is biphasic with alterations in cystic epithelia precipitating changes in interstitial fibroblasts and that reciprocal interactions between these cell types drives progressive accumulation of extracellular matrix (ECM). Since fibrosis is a major component of ADPKD it follows that preventing or slowing fibrosis should retard disease progression with obvious therapeutic benefits. The development of effective anti-fibrotic strategies in ADPKD is dependent on understanding the precise mechanisms underlying initiation and progression of fibrosis in ADPKD and the role of the intrinsic genetic defect in these processes. This article is part of a Special Issue entitled: Polycystic Kidney Disease.     

NCAM as a cystogenesis marker gene of PKD2 overexpression

ADPKD (Autosomal Dominant Polycystic Kidney Disease) is characterized by the progressive expansion of multiple cystic lesions in the kidneys. ADPKD is caused by mutations in Ed-pl. consider PKD1 and PKD2. Recently a relation between c-myc and the pathogenesis of ADPKD was reported. In addition, c-Myc is a downstream effector of PKD1. To identify the gene regulated by PKD2 and c-Myc, we performed gene expression profiling in PKD2 and c-Myc overexpressing cells using a human 8K cDNA microarray. NCAM (neuronal cell adhesion molecule) levels were significantly reduced in PKD2 overexpressing systems in vitro and in vivo. These results suggest that NCAM is an important molecule in the cystogenesis induced by PKD2 overexpression.     

Use of Cystatin C and Serum Creatinine for the Diagnosis of Contrast-Induced Nephropathy in Patients Undergoing Contrast-Enhanced Computed Tomography at an Oncology Centre

ObjectiveOur aim was to assess renal function using as laboratory measurements serum creatinine and cystatin C concentrations before and after administration of low-osmolarity (nonionic) iodinated contrast medium in patients with cancer undergoing computed tomography (CT).MethodsThis prospective study included 400 oncologic outpatients. Serum creatinine and cystatin C concentrations were measured before and 72 h after contrast administration. Glomerular filtration rates (GFRs) were estimated using serum creatinine–based [Modification of Diet in Renal Disease (MDRD) and Cockroft-Gault and cystatin C based (Larsson) equations. Exploratory data analysis was performed. The nonparametric Wilcoxon test was used to compare pre and post contrast of test results and estimated clearance. The confidence interval used in the analysis was 95%.ResultsCompared with the pre-contrast values, the mean serum creatinine concentration was significantly higher and average GFRs estimated using MDRD and Cockcroft-Gault equations were significantly lower after the administration of contrast (p <0.001). It was also observed a significant increase after contrast in the concentration of Cystatin C (p = 0.015). In addition, a decrease in GFR estimated using the average Larsson (p = 0.021) was observed between time points. However, none of the patients presented clinically significant nephropathy.ConclusionsAssessment using serum creatinine and cystatin C concentrations showed changes in renal function among patients with cancer undergoing contrast-enhanced CT examination in this study. No significant renal damage related to the use of low-osmolarity iodinated contrast medium of the type and dosage employed in this study was observed. This contrast medium is thus safe for use in patients with cancer.     

Polycystic kidney disease: The complexity of planar cell polarity and signaling during tissue regeneration and cyst formation

Autosomal Dominant Polycystic Kidney Disease (ADPKD) is an inherited systemic disease with intrarenal cystogenesis as its primary characteristic. A variety of mouse models provided information on the requirement of loss of balanced polycystin levels for initiation of cyst formation, the role of proliferation in cystogenesis and the signaling pathways involved in cyst growth and expansion. Here we will review the involvement of different signaling pathways during renal development, renal epithelial regeneration and cyst formation in ADPKD, focusing on planar cell polarity (PCP) and oriented cell division (OCD). This will be discussed in context of the hypothesis that aberrant PCP signaling causes cyst formation. In addition, the role of the Hippo pathway, which was recently found to be involved in cyst growth and tissue regeneration, and well-known for regulating organ size control, will be reviewed. The fact that Hippo signaling is linked to PCP signaling makes the Hippo pathway a novel cascade in cystogenesis. The newly gained understanding of the complex signaling network involved in cystogenesis and disease progression, not only necessitates refining of the current hypothesis regarding initiation of cystogenesis, but also has implications for therapeutic intervention strategies. This article is part of a Special Issue entitled: Polycystic Kidney Disease.     

Polycystin and calcium signaling in cell death and survival

Mutations in polycystin-1 (PC1) and polycystin-2 (PC2) result in a commonly occurring genetic disorder, called Autosomal Dominant Polycystic Kidney Disease (ADPKD), that is characterized by the formation and development of kidney cysts. Epithelial cells with loss-of-function of PC1 or PC2 show higher rates of proliferation and apoptosis and reduced autophagy. PC1 is a large multifunctional transmembrane protein that serves as a sensor that is usually found in complex with PC2, a calcium (Ca²⁺)-permeable cation channel. In addition to decreased Ca²⁺ signaling, several other cell fate-related pathways are de-regulated in ADPKD, including cAMP, MAPK, Wnt, JAK-STAT, Hippo, Src, and mTOR. In this review we discuss how polycystins regulate cell death and survival, highlighting the complexity of molecular cascades that are involved in ADPKD.     

Polycystins, focal adhesions and extracellular matrix interactions

Polycystic kidney disease is the most common heritable disease in humans. In addition to epithelial cysts in the kidney, liver and pancreas, patients with autosomal dominant polycystic kidney disease (ADPKD) also suffer from abdominal hernia, intracranial aneurysm, gastrointestinal cysts, and cardiac valvular defects, conditions often associated with altered extracellular matrix production or integrity. Despite more than a decade of work on the principal ADPKD genes, PKD1 and PKD2, questions remain about the basis of cystic disease and the role of extracellular matrix in ADPKD pathology. This review explores the links between polycystins, focal adhesions, and extracellular matrix gene expression. These relationships suggest roles for polycystins in cell-matrix mechanosensory signaling that control matrix production and morphogenesis. This article is part of a Special Issue entitled: Polycystic Kidney Disease.     

Comparison of the Schwartz and CKD-EPI Equations for Estimating Glomerular Filtration Rate in Children,Adolescents, and Adults: A Retrospective Cross-Sectional Study

Background

Estimating kidney glomerular filtration rate (GFR) is of utmost importance in many clinical conditions. However, very few studies have evaluated the performance of GFR estimating equations over all ages and degrees of kidney impairment. We evaluated the reliability of two major equations for GFR estimation, the CKD-EPI and Schwartz equations, with urinary clearance of inulin as gold standard.

Methods and Findings

The study included 10,610 participants referred to the Renal and Metabolic Function Exploration Unit of Edouard Herriot Hospital (Lyon, France). GFR was measured by urinary inulin clearance (only first measurement kept for analysis) then estimated with isotope dilution mass spectrometry (IDMS)–traceable CKD-EPI and Schwartz equations. The participants’ ages ranged from 3 to 90 y, and the measured GFRs from 3 to 160 ml/min/1.73 m². A linear mixed-effects model was used to model the bias (mean ratio of estimated GFR to measured GFR). Equation reliability was also assessed using precision (interquartile range [IQR] of the ratio) and accuracy (percentage of estimated GFRs within the 10% [P10] and 30% [P30] limits above and below the measured GFR). In the whole sample, the mean ratio with the CKD-EPI equation was significantly higher than that with the Schwartz equation (1.17 [95% CI 1.16; 1.18] versus 1.08 [95% CI 1.07; 1.09], p < 0.001, t-test). At GFR values of 60–89 ml/min/1.73 m², the mean ratios with the Schwartz equation were closer to 1 than the mean ratios with the CKD-EPI equation whatever the age class (1.02 [95% CI 1.01; 1.03] versus 1.15 [95% CI 1.13; 1.16], p < 0.001, t-test). In young adults (18–40 y), the Schwartz equation had a better precision and was also more accurate than the CKD-EPI equation at GFR values under 60 ml/min/1.73 m² (IQR: 0.32 [95% CI 0.28; 0.33] versus 0.40 [95% CI 0.36; 0.44]; P30: 81.4 [95% CI 78.1; 84.7] versus 63.8 [95% CI 59.7; 68.0]) and also at GFR values of 60–89 ml/min/1.73 m². In all patients aged ≥65 y, the CKD-EPI equation performed better than the Schwartz equation (IQR: 0.33 [95% CI 0.31; 0.34] versus 0.40 [95% CI 0.38; 0.41]; P30: 77.6 [95% CI 75.7; 79.5] versus 67.5 [95% CI 65.4; 69.7], respectively). In children and adolescents (2–17 y), the Schwartz equation was superior to the CKD-EPI equation (IQR: 0.23 [95% CI 0.21; 0.24] versus 0.33 [95% CI 0.31; 0.34]; P30: 88.6 [95% CI 86.7; 90.4] versus 29.4 [95% CI 26.8; 32.0]). This study is limited by its retrospective design, single-center setting with few non-white patients, and small number of patients with severe chronic kidney disease.

Conclusions

The results from this study suggest that the Schwartz equation may be more reliable than the CKD-EPI equation for estimating GFR in children and adolescents and in adults with mild to moderate kidney impairment up to age 40 y.     

Estimating renal function for drug dosing decisions

In order to adjust the dose of renally excreted drugs in response to reduced renal function, it is necessary to make a quantitative estimate of the glomerular filtration rate (GFR) of the patient. Traditionally this has been done with the use of the Cockcroft and Gault equation or a measured creatinine clearance. More recently the MDRD (Modification of Diet in Renal Disease) formula has become available, providing an estimate of GFR readily available on routine pathology reports. The presence of these different methods of assessing renal function has created some confusion for healthcare workers as to the best approach. In this paper the two methods are compared, together with a newer formula CKD-EPI (named after the Chronic Kidney Disease Epidemiology Collaborative), and a proposal is made for future practice.     

Inhibition of HER-2(neu/ErbB2) restores normal function and structure to polycystic kidney disease (PKD) epithelia

Autosomal Dominant Polycystic Kidney Disease (ADPKD) is a very common lethal monogenetic disease with significant morbidities and a high likelihood of progression to renal failure for which there is no proven disease-specific therapy currently available for clinical use. Human ADPKD cystic epithelia have proliferative abnormalities mediated by EGFR over-expression and mispolarization leading autocrine response to EGF family ligands. We now show that apical localization of EGFR complexes in normal fetal and ADPKD epithelia is associated with heterodimerization of EGFR(HER-1) with HER-2(neu/ErbB2), while basal membrane localization in normal adult renal epithelia is associated with EGFR(HER-1) homodimers. Since ADPKD epithelial cells have reduced migratory function, this was used as a bioassay to evaluate the ability of compounds to rescue the aberrant human ADPKD phenotype. General tyrosine kinase inhibition by herbimycin and specific inhibition of HER-2(neu/ErbB2) by AG825 or pretreatment with ErbB2 siRNA reversed the migration defect of ADPKD epithelia. Selective inhibition of EGFR(HER-1) showed partial rescue. Increased ADPKD cell migration after inhibition of p38MAP kinase but not of PI3-kinase implicated p38MAPK downstream of HER-2(neu/ErbB2) stimulation. Daily administration of AG825 to PKD1 null heterozygous mice significantly inhibited the development of renal cysts. These studies implicate HER2(neu/ErbB2) as an effector of apical EGFR complex mispolarization and that its inhibition should be considered a candidate for clinical therapy of ADPKD.     

Autosomal dominant polycystic kidney disease: Genetics, mutations and microRNAs

Autosomal dominant polycystic kidney disease (ADPKD) is a common, monogenic multi-systemic disorder characterized by the development of renal cysts and various extrarenal manifestations. Worldwide, it is a common cause of end-stage renal disease. ADPKD is caused by mutation in either one of two principal genes, PKD1 and PKD2, but has large phenotypic variability among affected individuals, attributable to PKD genic and allelic variability and, possibly, modifier gene effects. Recent studies have generated considerable information regarding the genetic basis and molecular diagnosis of this disease, its pathogenesis, and potential strategies for targeted treatment. The purpose of this article is to provide a comprehensive review of the genetics of ADPKD, including mechanisms responsible for disease development, the role of gene variations and mutations in disease presentation, and the putative role of microRNAs in ADPKD etiology. The emerging and important role of genetic testing and the advent of novel molecular diagnostic applications also are reviewed. This article is part of a Special Issue entitled: Polycystic Kidney Disease.     

KDIGO Categories of Glomerular Filtration Rate and Parathyroid Hormone Secretion in Primary Hyperparathyroidism

Objective: The recent Fourth Workshop on the Management of Asymptomatic primary hyperparathyroidism (PHPT) maintained the threshold of 60 mL/min for decreased renal function, below which surgery is recommended. This study investigated the relationship between different stages of renal insufficiency and parathyroid hormone (PTH) levels in an updated case series of PHPT patients.Methods: This was a retrospective, cross-sectional study involving 379 consecutive PHPT patients. Biochemical evaluation included total and ionized serum calcium, phosphate, creatinine, immunoreactive intact PTH, and 25-hydroxyvitamin D₃ (25[OH]D₃) levels in the fasting state. Glomerular filtration rate (GFR) was estimated using the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation.Results: Mean CKD-EPI estimated GFR was 81.9 ± 20.3 mL/min/1.73 m², and median GFR was 84.0 mL/min/1.73 m² (interquartile range, 26.8 mL/min/1.73 m²). The patients were divided into 5 groups according to the Kidney Disease: Improving Global Outcomes 2012 guidelines: group 1 with normal or increased GFR (>90 mL/min/1.73 m²); group 2 with mild GFR decrease (60 to 89 mL/min/1.73 m²); group 3a with mild to moderate GFR decrease (45 to 59 mL/min/1.73 m²); group 3b with moderate to severe GFR decrease (30 to 44 mL/min/1.73 m²); and group 4 with severe GFR decrease (<30 mL/min/1.73 m²). Among the 5 groups of patients, serum calcium levels were different (P = .025), whereas 25(OH)D₃ levels were not (P = .36). PTH levels were comparable across groups 1 through 3a, but they were significantly higher in groups 3b and 4 (P<.0001).Conclusion: In our series of PHPT patients, PTH levels did not rise as a result of renal impairment until GFR decreased below 45 mL/min/1.73 m².Abbreviations: 25(OH)D₃ = 25-hydroxyvitamin D₃ CKD-EPI = Chronic Kidney Disease-Epidemiology Collaboration GFR = glomerular filtration rate K/DOQI = National Kidney Foundation Disease Outcomes Quality Initiative KDIGO = Kidney Disease: Improving Global Outcomes MDRD = Modification of Diet in Renal Disease PHPT = primary hyperparathyroidism PTH = parathyroid hormone     

慢性肾脏病患者心脏结构与功能变化的超声心动图研究

目的:研究慢性肾脏病(CKD)患者心脏结构及功能的变化.方法:选择我院肾内科175例慢性肾脏病未透析患者,按照2003年美国国家肾脏基金会-肾脏病转归质量(NKF-K/DOQI)指南的标准进行分期,观察所有患者心脏结构及功能在超声中的变化.结果:慢性肾脏病患者随着肾功能的恶化,各组之间比较,室间隔厚度(IVST)、左心室后壁厚度(LVPW)、左心室心肌重量指数(LVMI)、左心室舒张末期内径(LVDd)、左心房内径(LAD)具有升高的趋势(P＜0.05,P＜0.01);但E/A比值未出现伴随着肾功能恶化而逐渐减低的趋势(P＞0.05);射血分数(EF)、短轴缩短卒(FS)在各期之间无明显变化(P＞0.05);而TVI技术测定的Em、Em/Am具有显著减低的趋势(P＜0.05,P＜0.01);瓣膜返流以二尖瓣返流为主.结论:慢性肾脏病患者心脏结构与功能随肾功能减退而加重,超声心动图检查结合组织速度显像(TVI)技术能更好地检测心脏结构和功能变化,尤其是检测左心室舒张功能障碍.     

Epidemiology of CKD Regression in Patients under Nephrology Care

Chronic Kidney Disease (CKD) regression is considered as an infrequent renal outcome, limited to early stages, and associated with higher mortality. However, prevalence, prognosis and the clinical correlates of CKD regression remain undefined in the setting of nephrology care. This is a multicenter prospective study in 1418 patients with established CKD (eGFR: 60–15 ml/min/1.73m²) under nephrology care in 47 outpatient clinics in Italy from a least one year. We defined CKD regressors as a ΔGFR ≥0 ml/min/1.73 m²/year. ΔGFR was estimated as the absolute difference between eGFR measured at baseline and at follow up visit after 18–24 months, respectively. Outcomes were End Stage Renal Disease (ESRD) and overall-causes Mortality.391 patients (27.6%) were identified as regressors as they showed an eGFR increase between the baseline visit in the renal clinic and the follow up visit. In multivariate regression analyses the regressor status was not associated with CKD stage. Low proteinuria was the main factor associated with CKD regression, accounting per se for 48% of the likelihood of this outcome. Lower systolic blood pressure, higher BMI and absence of autosomal polycystic disease (PKD) were additional predictors of CKD regression. In regressors, ESRD risk was 72% lower (HR: 0.28; 95% CI 0.14–0.57; p<0.0001) while mortality risk did not differ from that in non-regressors (HR: 1.16; 95% CI 0.73–1.83; p = 0.540). Spline models showed that the reduction of ESRD risk associated with positive ΔGFR was attenuated in advanced CKD stage. CKD regression occurs in about one-fourth patients receiving renal care in nephrology units and correlates with low proteinuria, BP and the absence of PKD. This condition portends better renal prognosis, mostly in earlier CKD stages, with no excess risk for mortality.     

Multicenter Epidemiological Study to Assess the Population of CKD Patients in Greece: Results from the PRESTAR Study

Background

Chronic Kidney Disease (CKD) is a relatively common condition not only associated with increased morbidity and mortality but also fuelling End Stage Renal Disease (ESRD). Among developed nations, Greece has one of the highest ESRD incidence rates, yet there is limited understanding of the epidemiology of earlier stages of CKD.

Methods

Cross-sectional survey of pre-dialysis CKD outpatients in nephrology clinics in the National Health Care system between October 2009 and October 2010. Demographics, cause of CKD, blood pressure, level of renal function, duration of CKD and nephrology care, and specialty of referral physician were collected and analyzed. Different methods for estimating renal function (Cockroft-Gault [CG], CKD-Epi and MDRD) and staging CKD were assessed for agreement.

Results

A total of 1,501 patients in 9 centers were enrolled. Diabetic nephropathy was the most common nephrologist assigned cause of CKD (29.7%). In total, 36.5% of patients had self-referred to the nephrologist; patients with diabetes or serum creatinine above 220 µmol/l (eGFR<40 ml/min/1.73 m²) were more likely to have been referred by a physician. Agreement between MDRD and CKD-Epi, but not between CG, the other estimating equations, was excellent. There was substantial heterogeneity with respect to renal diagnoses, referral patterns and blood pressure among participating centers.

Conclusions

In this first epidemiologic assessment of CKD in Greece, we documented delayed referral and high rates of self-referral among patients with CKD. eGFR reporting, currently offered by a limited number of laboratories, may facilitate detection of CKD at an earlier, more treatable stage.     

Epigenetics and autosomal dominant polycystic kidney disease

The roles of epigenetic modulation of gene expression and protein functions in autosomal dominant polycystic kidney disease (ADPKD) have recently become the focus of scientific investigation. Evidence generated to date indicates that one of the epigenetic modifiers, histone deacetylases (HDACs), are important regulators of ADPKD. HDACs are involved in regulating the expression of the Pkd1 gene and are the target of fluid flow-induced calcium signal in kidney epithelial cells. Pharmacological inhibition of HDAC activity has been found to reduce the progression of cyst formation and slow the decline of kidney function in Pkd1 conditional knockout mice and Pkd2 knockout mice, respectively, implicating the potential clinical application of HDAC inhibitors on ADPKD. Since the expression of HDAC6 is upregulated in cystic epithelial cells, the potential roles of HDAC6 in regulating cilia resorption and epidermal growth factor receptor (EGFR) trafficking through deacetylating α-tubulin and regulating Wnt signaling through deacetylating β-catenin are also discussed. This article is part of a Special Issue entitled: Polycystic Kidney Disease.     

Polycystic kidney disease: Pathogenesis and potential therapies

Autosomal dominant polycystic kidney disease (ADPKD) is a prevalent, inherited condition for which there is currently no effective specific clinical therapy. The disease is characterized by the progressive development of fluid-filled cysts derived from renal tubular epithelial cells which gradually compress the parenchyma and compromise renal function. Current interests in the field focus on understanding and exploiting signaling mechanisms underlying disease pathogenesis as well as delineating the role of the primary cilium in cystogenesis. This review highlights the pathogenetic pathways underlying renal cyst formation as well as novel therapeutic targets for the treatment of PKD. This article is part of a Special Issue entitled: Polycystic Kidney Disease.     

Physical Activity Is not Associated with Estimated Glomerular Filtration Rate among Young and Middle-Aged Adults: Results from the Population-Based Longitudinal Doetinchem Study

There is debate as to whether physical inactivity is associated with reduced kidney function. We studied the prospective association of (changes in) physical activity with estimated glomerular filtration rate (eGFR) in adult men and women. We included 3,935 participants aged 26 to 65 years from the Doetinchem Cohort study, examined every 5 years for 15 years. Physical activity was assessed at each round using the Cambridge Physical Activity Index. Using the CKD-EPI (Chronic Kidney Disease Epidemiology Collaboration) equation, GFR was estimated from routinely measured cystatin C concentrations, examining all available samples per participant in one assay run. We determined the association between 1) physical activity and eGFR and 2) 5-year changes in physical activity (becoming inactive, staying inactive, staying active, becoming active) and eGFR, using time-lagged generalized estimating equation analyses. At baseline, 3.6% of the participants were inactive, 18.5% moderately inactive, 26.0% moderately active, and 51.9% active. The mean (± SD) eGFR was 107.9 (± 14.5) mL/min per 1.73 m². Neither physical activity nor 5-year changes in physical activity were associated with eGFR at the subsequent round. The multivariate adjusted βeGFR was 0.57 mL/min per 1.73 m² (95% Confidence Interval (CI) -1.70, 0.56) for inactive compared to active participants. Studying changes in physical activity between rounds, the adjusted βeGFR was -1.10 mL/min per 1.73 m² (95% CI -4.50, 2.30) for those who stayed inactive compared with participants who became active. Physical activity was not associated with eGFR in this population-based study of adults.