Objective: The aim of this study was to determine the prevalence of micro- or macroalbuminuria among type 1 and type 2 diabetic patients and to examine the relationship with diabetes control parameters: haemoglobin A1C (HbA1C), blood pressure (BP) and lipids. Design: Analytical cross-sectional study. Setting and subjects: The study consisted of 754 patients with either type 1 or type 2 diabetes mellitus, attending a diabetic clinic at the Kalafong Hospital in Pretoria, South Africa. Outcome measures: Micro- or macroalbuminuria and estimated glomerular filtration rate (eGFR). Results: Of all patients, 88.9% had HbA1C > 7%, and 81% had low-density lipoprotein (LDL) cholesterol ≥1.8 mmol/l. Overall prevalence of micro- or macroalbuminuria was 33.6%. Logistic regression revealed that HbA1C, duration of diabetes, systolic BP, male sex and triglycerides predicted microalbuminuria. Conclusion: The prevalence of micro- or macroalbuminuria in this study falls within the ranges of what has been previously reported in Africa. In all patients, HbA1C and duration of diabetes were the strongest predictors of microalbuminuria, and age was the strongest predictor of a low eGFR. Diabetes was poorly controlled, making the progression to end-stage renal failure a real concern in these patients. / Dissertation (MPH)--University of Pretoria, 2015. / tm2015 / School of Health Systems and Public Health (SHSPH) / MPH / Unrestricted

National Kidney Disease Education Program has initiated a serum creatinine standardization program. Glomerular filtration rate (GFR) can be re-estimated from standardized serum creatinine measurements. How the standardized estimated GFR (eGFR) influences hypertension prevalence has not been evaluated. In this study, cross-sectional data from 21 205 participants aged 18 years in the National Health and Nutrition Examination Survey 1999-2006 were analyzed. The differences between standardized and non-standardized eGFRs in the prevalence of hypertension and low eGFR were evaluated. Multiple logistic regression models were conducted to determine the association of standardized eGFR with hypertension prevalence. The prevalence of low eGFR estimated from standardized eGFR was higher than that from non-standardized eGFR (all P0.01), except for the 2005-2006 survey. The prevalence of hypertension under standardized eGFR was not significantly different from that under non-standardized eGFR in both groups of participants with eGFR60 and eGFR60 ml min 1 per 1.73 m 2. Adjusted for age, education, gender, race/ethnicity, smoking, serum cholesterol and diabetes mellitus, the participants with standardized eGFR60 ml min 1 per 1.73 m 2 had 56.1% more chance to be hypertensive patients than those with normal eGFR (P0.0001). The difference in the relationship to hypertension prevalence between standardized and non-standardized eGFR was not found significant.

Background: There is a 3-fold risk of developing end stage kidney disease in Non-Hispanic African Americans compared to Non-Hispanic White Americans (Centers for Disease Control and Prevention, 2017). Estimated glomerular filtration rate (eGFR), one of the fundamental algorithms for coordinating treatment for kidney disease which factors in age, race, gender, and levels of creatinine, may pose an issue in this vulnerable population. Currently African Americans receive a correction factor between 1.21 and 1.16 to their eGFR to adjusting the value higher, potentially impacting appropriate kidney disease classification, and delaying beneficial interventions (National Kidney Foundation, 2020). Methods: A systematic literature search of four databases was completed. Eligibility criteria included 1) published in a peer reviewed journal, 2) English language, 3) the use of race correction in calculating eGFR, and 4) a quantitative study design. A total of 47 articles were screened with 17 selected for final review. The Johns-Hopkins Nursing Evidence - Based Practice evidence guide was then used to rate the strength and quality of the evidence. Results: Early evidence of the unreliability of race based eGFR equations emerged in 2008, and the body of evidence continues to grow. Recent studies have found eGFR calculated with no race corrections correlate best with directly measured iothalmate GFR in black patients (Zelnick et al., 2021), and that a potential 1,066,026 Black Americans may be reclassified to a more severe stage of CKD (Bragg-Gresham et al., 2021). Use of the race correction in GFR equations has been poorly supported in studies conducted in Africa and Brazil. For those with HIV, an accurate eGFR is doubly important yet all eGFR equations have marked variability. Some medical facilities have successfully updated to calculating eGFR without the racial coefficient (Shi et al., 2021). Conclusion: Nurses should be aware of the implications of using race correction in eGFR equations, educate their patients on its use, and advocate for those near threshold targets to ensure equitable and timely access to appropriate kidney disease interventions.

Yes / Acute kidney injury (AKI) can occur rarely in patients exposed to iodinated contrast and result in contrast-induced AKI (CI-AKI). A key risk factor is the presence of pre-existing chronic kidney disease (CKD), therefore it is important to assess patient risk and obtain kidney function measurement prior to administration. Point of care (PoC) testing provides an alternative strategy but there remains uncertainty, with respect to diagnostic accuracy and clinical utility. A device study compared three PoC analysers (Nova StatSensor, Abbott i-STAT, Radiometer ABL800 FLEX) with a reference laboratory standard (Roche Cobas 8000 series, enzymatic creatinine). Three hundred adult patients attending a UK hospital phlebotomy department were recruited to have additional blood samples for analysis on the PoC devices. The ABL800 FLEX had the strongest concordance with laboratory measured serum creatinine (mean bias=-0.86, 95% limits of agreement = -9.6 to 7.9) followed by the i-STAT (average bias=3.88, 95% limits of agreement = -8.8 to 16.6) and StatSensor (average bias=3.56, 95% limits of agreement = -27.7 to 34.8). In risk classification, the ABL800 FLEX and i-STAT identified all patients with an eGFR≤30, whereas the StatSensor resulted in a small number of missed high-risk cases (n=4/13) and also operated outside of the established performance goals. The screening of patients at risk of CI-AKI may be feasible with PoC technology. However in this study it was identified that the analyser concordance with the laboratory reference varies. It is proposed that further research exploring PoC implementation in imaging department pathways is needed. / Yorkshire and Humber Academic Health Science Network (Grant Number: YHP0318)

Hypertension artérielle résistante et maladie rénale chronique : Déterminants et risques associésL’hypertension résistante, définie par une pression artérielle au-dessus de la cible en dépit de la prise de trois antihypertenseurs à dose optimale dont un diurétique, est fréquemment associée à la maladie rénale chronique (MRC). Sa prévalence, ses déterminants et l’impact potentiel de la MRC sur son pronostic à long terme sont mal connus, notamment chez le sujet âgé. Dans l’étude des 3 cités, incluant 4262 personnes de plus de 65 ans traitées pour hypertension, la prévalence de l’hypertension apparemment résistante (HTAR) - la notion de traitement à dose optimale étant inconnue - était de 11,8% vs 5,2% chez ceux avec vs sans MRC (définie par une fonction rénale < 60 mL/min/1.73 m2). Nous avons montré que l’apparition d’une HTAR était plus fortement liée à la rapidité du déclin annuel de la fonction rénale qu’à son niveau, indépendamment des autres facteurs de risque : obésité, diabète, sexe masculin, antécédent cardiovasculaire. Comparé au groupe de référence (avec hypertension contrôlée et sans MRC), les personnes avec une HTAR et une MRC n’avaient pas de risque significativement plus élevé de mortalité toute cause, mais avaient deux fois plus de risque d’accident vasculaire cérébral (AVC), létal ou non, et de récurrence d’un AVC ou d’un événement coronaire, et trois fois plus de décès coronaire. Cependant, l’’hypothèse d’un effet aggravant de la MRC sur le pronostic de l’HTAR n’a pas été confirmé (interaction non significative).Dans la cohorte CKD-REIN, incluant plus de 3000 patients avec une MRC modérée ou avancée suivis en néphrologie (âge moyen, 70 ans, 60% d’hommes), nos résultats préliminaires montrent une prévalence élevée d’HTAR, 36,7%, et plusieurs facteurs de risque potentiellement modifiables : adhérence médiocre au traitement, absence de diurétique, consommation de sel en excès, obésité.Dans l’ensemble, ces travaux montrent l’importance de la MRC dans le développement de l’HTAR et des risques cardiovasculaires associés, et suggère des moyens de prévention au-delà des traitements médicamenteux. / Resistant hypertension and chronic kidney disease: Determinants and outcomesResistant hypertension defined as blood pressure above goal despite simultaneous use of 3 antihypertensive classes at optimal doses including a diuretic, is commonly associated with chronic kidney disease (CKD). Resistant hypertension prevalence and determinants, and the impact of CKD on its long term outcomes are poorly known, particularly in the elderly population.In the 3 Cities cohort, including 4262 community-dwelling elderly individuals, aged 65 years or older treated for hypertension, the prevalence of apparent treatment resistant hypertension (aTRH) – because of lack of information on optimal treatment dose – was 11.8% vs 5.2% in those with vs without CKD (defined as estimated glomerular filtration rate < 60 mL/min/1.73 m2). We showed that new-onset aTRH was more strongly related to the speed of kidney function decline than kidney function level itself, independent of other risk factors: male sex, obesity, diabetes, and history of cardiovascular disease. Compared to the reference group (with controlled hypertension and no CKD), participants with aTRH and CKD had no significantly higher risk of all-cause mortality, but had a risk of fatal or non-fatal stroke and of recurrent stroke or coronary events more than twice as high, and of coronary death more than three times higher. However, the hypothesis that CKD may worsen the prognosis of aTRH was not confirmed (no significant interaction).In the CKDREIN cohort, which included more than 3000 nephrology outpatients with moderate or severe CKD (mean age, 70 years, 60% of men), our preliminary results showed a high prevalence of aTRH, 36,7% and several potentially modifiable risk factors : poor treatment adherence, lack of diuretic use, excess salt intake and obesity.Overall, this work shows the importance of CKD in the development of aTRH and associated cardiovascular outcomes, and suggests means for prevention beyond drug therapy.

Background: Higher protein diets, especially from animal sources, have seen a rise in popularity due to potential metabolic. This may have consequences for kidney function particularly in rising middle class populations who are allocating more income towards meat. The objective of this systematic review and meta-analysis was to evaluate the effects of higher versus lower protein intake on glomerular filtration rate (GFR) in adult populations without renal impairment. Methods: Search strategies were developed and electronic databases searched: MEDLINE and EMBASE. Data were extracted up until June 3, 2015. The main outcome measure was GFR and a random effect model (Cochrane’s Review Manager Version 5.3) was used to pool mean differences in GFR values. Results: Database searches yielded 25 trials from 1914 articles that were eligible for analysis based on inclusion/exclusion criteria. 12 studies were randomized controlled trials and 11 studies were crossover trials. As a result of data presented, 2 crossover studies were treated as 4 trials to result in 25 total trials. A total of 810 subjects from 25 trials were included in this systematic review and meta-analyses. The age of participants was 24-62 years and their BMI was 21-36 kg/m2. Higher protein compared to lower protein-containing diets were associated with increased GFR values [mean difference (MD): 8.33 ml/min (95% CI 4.87 to 11.79), P < 0.00001] but this was less pronounced when assessing change from baseline GFR values [MD: 4.71 ml/min (95% CI 0.06 to 9.36), P = 0.05]. Moreover, significant heterogeneity was present and funnel plot asymmetry indicated potential publication bias in both meta-analyses. Conclusion: Higher protein diets were associated with increased GFR, however, these results were inconclusive due to significant heterogeneity and overestimation by random effect analyses. There is still no clear evidence that high protein diets negatively impact renal function in healthy populations. / Thesis / Master of Science (MSc) / Globally, the leading causes of mortality in industrialized countries are cardiovascular disease (CVD), stroke, and type 2 diabetes (T2D). Deaths from these chronic diseases now outpace deaths due to malnutrition. Being overweight and obese increases the risk of both morbidity and mortality from CVD, stroke, and T2D. Global rates of overweight and obesity have now reached ‘epidemic’ proportions and the World Health Organization has stated that, “… [a] global epidemic of overweight and obesity – ‘globesity’ – is taking over many parts of the world. If immediate action is not taken, millions will suffer from an array of serious health disorders.” Over the past 20-30 years, the popularity of higher protein energy restricted diets have grown due to the potential benefits regarding weight loss, appetite regulation, and maintenance of lean (muscle) mass. Additionally, the expansion of the global ‘middle-class’ has resulted in families allocating more income towards meat products as a primary protein source in their diet. A health concern is that higher protein intake may have an adverse effect on kidney function. In individuals with chronic kidney disease, higher protein diets have been shown to result in further renal impairment. However, the effects of increased protein intake in healthy populations are unclear. The aim of this systematic review and meta-analysis was to compare higher versus lower protein diets on kidney function in healthy populations based on the literature to date. This was accomplished by looking at changes in glomerular filtration rate (the rate at which kidneys filter blood), which is the ‘gold standard’ marker of kidney function.

Le virus de l'immunodéficience humaine (VIH) est à l’origine d’une infection chronique, elle-même responsable du développement du syndrome d'immunodéficience acquise (SIDA), un état de grande vulnérabilité où le corps humain est à la merci d’infections opportunistes pouvant s’avérer fatales. Aujourd’hui, 30 ans après la découverte du virus, même si aucun vaccin n’a réussi à contrôler la pandémie, la situation s’est grandement améliorée. Conséquemment à l’arrivée de traitements antirétroviraux hautement actifs (HAART) à la fin des années 1990, la mortalité associée au VIH/SIDA a diminué et un plus grand nombre de personnes vivent maintenant avec l'infection. La présente thèse avait pour objectif d’aborder trois situations problématiques, en dépit de l’efficacité reconnue des HAART, plus particulièrement la faible charge virale persistante (LLV) et sa relation avec l’échec virologique, ainsi que les effets de certains antirétroviraux (ARV) sur les fonctions rénale et hépatique. Les objectifs précis étaient donc les suivants : 1) étudier le risque d’échec virologique à long terme chez les patients sous HAART dont la charge virale est indétectable comparativement aux patients affichant une LLV persistante; 2) évaluer sur le long terme la perte de fonction rénale associée à la prise de ténofovir (TDF) 3) étudier sur le long terme l'hyperbilirubinémie associée à la prise d’atazanavir (ATV) et ses autres déterminants possibles. Afin d’atteindre les trois objectifs susmentionnés, une cohorte de 2 416 patients atteints du VIH/SIDA, suivis depuis juillet 1977 et résidant à Montréal, a été utilisée. Pour le premier objectif, les résultats obtenus ont montré un risque accru d’échec virologique établi à >1000 copies/ml d’ARN VIH chez tous les patients qui présentaient une LLV persistante de différentes catégories durant aussi peu que 6 mois. En effet, on a observé qu’une LLV de 50-199 copies/ml persistant pendant six mois doublait le risque d’échec virologique (Hazard ratio (HR)=2,22, Intervalle de confiance (CI) 95 %:1,60–3,09). Ces résultats pourraient modifier la façon dont on aborde actuellement la gestion des patients affichant une LLV, et plus particulièrement une LLV de 50-199 copies/ml, pour laquelle aucune recommandation clinique n’a encore été formulée en raison du manque de données. Pour le deuxième objectif, on a observé une augmentation du risque de perte de fonction rénale de l’ordre de 63 % (HR=1,63; 95% CI:1,26–2,10) chez les patients sous TDF comparativement aux patients traités avec d’autres ARV. La perte de fonction rénale directement attribuable à la prise de TDF, indique que cette perte est survenue au cours des premières années de l’exposition du patient au médicament. D’une perspective à long terme, cette perte est considérée comme modérée. Enfin, pour ce qui est du troisième objectif, on a constaté que l’incidence cumulative d’hyperbilirubinémie était très élevée chez les patients sous ATV, mais que cette dernière pouvait régresser lorsque l’on mettait fin au traitement. L’hyperbilirubinémie à long terme observée avec la prise d’ATV n’a été associée à aucun effet néfaste pour la santé. Dans l’ensemble, la présente thèse a permis de mieux comprendre les trois situations problématiques susmentionnées, qui font actuellement l’objet de débats au sein de la communauté scientifique, et d’éclairer sous un jour nouveau la gestion des patients séropositifs sous traitement médicamenteux. / Human immonudeficiency virus (HIV) is a virus causing a chronic infection responsible for Acquired Immunodeficiency Syndrome (AIDS), a state of vulnerability of the body where different opportunistic infections will ultimately be fatal. About 30 years after the discovery of the virus, even if no vaccine is available to control the pandemia, situation has changed for the best. With the arrival of highly active anti-retroviral therapy (HAART) in the late 90's, a reduction in HIV/AIDS mortality rate and growing number of persons living with the infection were observed. The overall objective of this thesis was to address three problematic situations, despite recognised HAART efficacy, especially low-level viremia (LLV) and its relationship with virologic failure, and the impacts of certain antiretrovirals (ARV) on kidney and hepatic functions. The specific objectives were: 1) to study the risk of virologic failure in long-term perspective in undetectable patients under HAART in comparison to patients with persistent LLV; 2) to evaluate the long-term loss of kidney function related to tenofovir (TDF) exposure 3) to evaluate long-term hyperbilirubinemia related to atazanavir (ATV) exposure and other possible determinants. In order to address the three specific objectives, a cohort of patients 2416 living with HIV/AIDS followed in Montreal since July 1977 was used. For the first objective, analyses and results shown an increased risk of virological failure defined as >1000 copies/mL of HIV RNA, for all categories of persistent LLV as soon as 6 months of persistent duration. Persistent LLV of 50-199 copies/mL for 6 months doubled the risk of virologic failure (Hazard ratio (HR)=2,22, Confidence interval (CI) 95%: 1,60-3,09). The results shed new light for the management of patients with LLV, especially for LLV of 50-199 copies/mL, for which no clinical recommendation is currently available due to a lack of data. For the second objective, an increased risk of loss of kidney function of 63% (HR=1.63; 95% CI:1.26–2.10) associated to TDF exposure in comparison to patients taking other ARV was observed. The cumulative eGFR loss directly attribuable to TDF also shown that this loss occured during the first years of exposure. This loss was mild in a long-term perspective. For the third objective, it has been shown that the cumulative incidence of hyperbilirubinemia in ATV users was very high and that regression was possible if ATV exposure was ended. Long-term hyperbilirubinemia related to ATV use was not associated with adverse health outcome. Overall, this thesis allowed a better understanding of these three problematics currently debated in scientific literature and shed new lights on management of HIV positive patients under therapy.

Le virus de l'immunodéficience humaine (VIH) est à l’origine d’une infection chronique, elle-même responsable du développement du syndrome d'immunodéficience acquise (SIDA), un état de grande vulnérabilité où le corps humain est à la merci d’infections opportunistes pouvant s’avérer fatales. Aujourd’hui, 30 ans après la découverte du virus, même si aucun vaccin n’a réussi à contrôler la pandémie, la situation s’est grandement améliorée. Conséquemment à l’arrivée de traitements antirétroviraux hautement actifs (HAART) à la fin des années 1990, la mortalité associée au VIH/SIDA a diminué et un plus grand nombre de personnes vivent maintenant avec l'infection. La présente thèse avait pour objectif d’aborder trois situations problématiques, en dépit de l’efficacité reconnue des HAART, plus particulièrement la faible charge virale persistante (LLV) et sa relation avec l’échec virologique, ainsi que les effets de certains antirétroviraux (ARV) sur les fonctions rénale et hépatique. Les objectifs précis étaient donc les suivants : 1) étudier le risque d’échec virologique à long terme chez les patients sous HAART dont la charge virale est indétectable comparativement aux patients affichant une LLV persistante; 2) évaluer sur le long terme la perte de fonction rénale associée à la prise de ténofovir (TDF) 3) étudier sur le long terme l'hyperbilirubinémie associée à la prise d’atazanavir (ATV) et ses autres déterminants possibles. Afin d’atteindre les trois objectifs susmentionnés, une cohorte de 2 416 patients atteints du VIH/SIDA, suivis depuis juillet 1977 et résidant à Montréal, a été utilisée. Pour le premier objectif, les résultats obtenus ont montré un risque accru d’échec virologique établi à >1000 copies/ml d’ARN VIH chez tous les patients qui présentaient une LLV persistante de différentes catégories durant aussi peu que 6 mois. En effet, on a observé qu’une LLV de 50-199 copies/ml persistant pendant six mois doublait le risque d’échec virologique (Hazard ratio (HR)=2,22, Intervalle de confiance (CI) 95 %:1,60–3,09). Ces résultats pourraient modifier la façon dont on aborde actuellement la gestion des patients affichant une LLV, et plus particulièrement une LLV de 50-199 copies/ml, pour laquelle aucune recommandation clinique n’a encore été formulée en raison du manque de données. Pour le deuxième objectif, on a observé une augmentation du risque de perte de fonction rénale de l’ordre de 63 % (HR=1,63; 95% CI:1,26–2,10) chez les patients sous TDF comparativement aux patients traités avec d’autres ARV. La perte de fonction rénale directement attribuable à la prise de TDF, indique que cette perte est survenue au cours des premières années de l’exposition du patient au médicament. D’une perspective à long terme, cette perte est considérée comme modérée. Enfin, pour ce qui est du troisième objectif, on a constaté que l’incidence cumulative d’hyperbilirubinémie était très élevée chez les patients sous ATV, mais que cette dernière pouvait régresser lorsque l’on mettait fin au traitement. L’hyperbilirubinémie à long terme observée avec la prise d’ATV n’a été associée à aucun effet néfaste pour la santé. Dans l’ensemble, la présente thèse a permis de mieux comprendre les trois situations problématiques susmentionnées, qui font actuellement l’objet de débats au sein de la communauté scientifique, et d’éclairer sous un jour nouveau la gestion des patients séropositifs sous traitement médicamenteux. / Human immonudeficiency virus (HIV) is a virus causing a chronic infection responsible for Acquired Immunodeficiency Syndrome (AIDS), a state of vulnerability of the body where different opportunistic infections will ultimately be fatal. About 30 years after the discovery of the virus, even if no vaccine is available to control the pandemia, situation has changed for the best. With the arrival of highly active anti-retroviral therapy (HAART) in the late 90's, a reduction in HIV/AIDS mortality rate and growing number of persons living with the infection were observed. The overall objective of this thesis was to address three problematic situations, despite recognised HAART efficacy, especially low-level viremia (LLV) and its relationship with virologic failure, and the impacts of certain antiretrovirals (ARV) on kidney and hepatic functions. The specific objectives were: 1) to study the risk of virologic failure in long-term perspective in undetectable patients under HAART in comparison to patients with persistent LLV; 2) to evaluate the long-term loss of kidney function related to tenofovir (TDF) exposure 3) to evaluate long-term hyperbilirubinemia related to atazanavir (ATV) exposure and other possible determinants. In order to address the three specific objectives, a cohort of patients 2416 living with HIV/AIDS followed in Montreal since July 1977 was used. For the first objective, analyses and results shown an increased risk of virological failure defined as >1000 copies/mL of HIV RNA, for all categories of persistent LLV as soon as 6 months of persistent duration. Persistent LLV of 50-199 copies/mL for 6 months doubled the risk of virologic failure (Hazard ratio (HR)=2,22, Confidence interval (CI) 95%: 1,60-3,09). The results shed new light for the management of patients with LLV, especially for LLV of 50-199 copies/mL, for which no clinical recommendation is currently available due to a lack of data. For the second objective, an increased risk of loss of kidney function of 63% (HR=1.63; 95% CI:1.26–2.10) associated to TDF exposure in comparison to patients taking other ARV was observed. The cumulative eGFR loss directly attribuable to TDF also shown that this loss occured during the first years of exposure. This loss was mild in a long-term perspective. For the third objective, it has been shown that the cumulative incidence of hyperbilirubinemia in ATV users was very high and that regression was possible if ATV exposure was ended. Long-term hyperbilirubinemia related to ATV use was not associated with adverse health outcome. Overall, this thesis allowed a better understanding of these three problematics currently debated in scientific literature and shed new lights on management of HIV positive patients under therapy.