| 1. |
- Afghahi, Henri, 1966
(författare)
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Epidemiological Aspects of Renal Impairment in Patients with Type 2 Diabetes
- 2016
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Diabetes is a leading cause of renal impairment (RI) and indication of the need for renal replacement therapy in many parts of the world. Albuminuria and RI are the two main forms of diabetic kidney disease. The overall aims of this thesis were to explore risk factors and consequences associated with albuminuria and RI in patients with type 2 diabetes (T2D), as well as to assess the relationship between blood pressure variables, cardiovascular events and all-cause mortality. The studies were based on data from the Swedish National Diabetes Register (NDR). Study I followed 3,367 patients with T2D who did not exhibit signs of albuminuria or RI from 2002 to 2007 in order to evaluate the risk of developing them. A total of 20% of patients developed albuminuria and 11% developed RI. Among those with one of the two conditions, 62% had normoalbuminuric RI. Development of albuminuria or RI was independently associated with advanced older age, high systolic blood pressure and elevated triglycerides. The independent risk factors were obesity, poor glycemic control, smoking, low HDL- cholesterol and male gender for developing albuminuria, as opposed to elevated plasma creatinine at baseline and female gender for developing RI. Different sets of risk factors were associated with development of the two conditionsRI and albuminuria. High body mass index (BMI) was an independent risk factor for RI when renal function was calculated with the MDRD equation, while low BMI was a risk factor with when the Cockcroft-Gault equation was used. In other words, the equation chosen to estimate renal function is important in when interpreting data. Thus, patients with T2D face have distinct risk factors for albuminuria and RI. Study II included 94,446 patients with T2D, including 19,330 with RI. The majority with T2D and RI were normoalbuminuric. Normoalbuminuric RI may be partly due to treatment with RAAS blockade. Given, however, that only 25% of the patients with normoalbuminuric renal impairment had received RAAS blockade, the possibility that other underlying pathophysiological mechanisms play a role should be further evaluated. Study III followed 33,356, and Study IV 27,732, patients with T2D and RI in 2005-2011 in order to evaluate correlations associations between systolic blood pressure (SBP) and all-cause mortality. We observed U-shaped relationships between various aspects of SBP and the risk of all-cause mortality. The greatest risks for Cardiovascular events (CVEs) and all-cause mortality were at the highest and lowest blood pressure intervals. SBP of 135-139 and diastolic blood pressure (DBP) of 72-74 mmHg showed the lowest risks of CVEs and all-cause mortality. Adjusting for presence of albuminuria or chronic heart failure did not significantly alter the results. A reduction in SBP during follow-up is was associated with a greater risk of all-cause mortality. In summary, this thesis shows that obesity and other traditional cardiovascular risk factors are associated with development of albuminuria and RI in patients with T2D. We also found that normoalbuminuric RI is common in patientsly associated with T2D. Finally, both the highest and lowest blood pressure intervals are associated with greater risks of cardiovascular events and all-cause mortality.
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| 2. |
- Afghahi, Henri, 1966, et al.
(författare)
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Long-term glycemic variability and the risk of mortality in diabetic patients receiving peritoneal dialysis.
- 2022
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Ingår i: PloS one. - : Public Library of Science (PLoS). - 1932-6203. ; 17:1
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Tidskriftsartikel (refereegranskat)abstract
- The large amount of glucose in the dialysate used in peritoneal dialysis (PD) likely affects the glycemic control. The aim of this study was to investigate the association between HbA1c variability, as a measure of long-term glycemic variability, and the risk of all-cause mortality in diabetic patients with PD.325 patients with diabetes and ESRD were followed (2008-2018) in the Swedish Renal Registry. Patients were separated in seven groups according to level of HbA1c variability. The group with the lowest variability was denoted the reference. The ratio of the standard deviation (SD) to the mean of HbA1c, HbA1c (SD)/HbA1c (mean), i.e. the coefficient of variation (CV), was defined as HbA1c variability. Hazard ratios (HR) and 95% confidence intervals (CI) were examined using Cox regression analyses.During follow-up, 170 (52%) deaths occurred. The highest mortality was among patients with the second highest HbA1c variability, CV≥2.83 [n = 44 of which 68% patients died]. In the multivariate analyses where lowest HbA1c variability (CV≤0.51) was used as the reference group, HbA1c CV 2.83-4.60 (HR 3.15, 95% CI 1.78-5.55; p<0.001) and CV> 4.6 (HR 2.48, 95% CI 1.21-5.11; p = 0.014) were associated with increased risk of death.The high risk of all-cause mortality in patients with diabetes and PD increased significantly with elevated HbA1c variability, as measure of long-term glycemic control. This indicates that stable glycemia is associated with an improvement of survival; whereas more severe glycemic fluctuations, possibly caused by radical changes in dialysis regimes or peritonitis, are associated with a higher risk of mortality in diabetic patients with PD.
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| 3. |
- Afghahi, Henri, 1966, et al.
(författare)
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Ongoing treatment with renin-angiotensin-aldosterone-blocking agents does not predict normoalbuminuric renal impairment in a general type 2 diabetes population.
- 2013
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Ingår i: Journal of diabetes and its complications. - : Elsevier BV. - 1873-460X .- 1056-8727. ; 27:3, s. 229-34
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Tidskriftsartikel (refereegranskat)abstract
- AIM: To examine the prevalence and the clinical characteristics associated with normoalbuminuric renal impairment (RI) in a general type 2 diabetes (T2D) population. METHODS: We included 94 446 patients with T2D (56% men, age 68.3±11.6years, BMI 29.6±5.3kg/m(2), diabetes duration 8.5±7.1years; means±SD) with renal function (serum creatinine) reported to the Swedish National Diabetes Register (NDR) in 2009. RI was defined as estimated glomerular filtration (eGFR)<60ml/min/1.73m(2) and albuminuria as a urinary albumin excretion rate (AER)>20μg/min. We linked the NDR to the Swedish Prescribed Drug Register, and the Swedish Cause of Death and the Hospital Discharge Register to evaluate ongoing medication and clinical outcomes. RESULTS: 17% of the patients had RI, and 62% of these patients were normoalbuminuric. This group of patients had better metabolic control, lower BMI, lower systolic blood pressure and were more often women, non-smokers and more seldom had a history of cardiovascular disease as compared with patients with albuminuric RI. 28% of the patients with normoalbuminuric RI had no ongoing treatment with any RAAS-blocking agent. Retinopathy was most common in patients with RI and albuminuria (31%). CONCLUSIONS: The majority of patients with type 2 diabetes and RI were normoalbuminuric despite the fact that 25% of these patients had no ongoing treatment with RAAS-blocking agents. Thus, RI in many patients with type 2 diabetes is likely to be caused by other factors than diabetic microvascular disease and ongoing RAAS-blockade.
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| 4. |
- Afghahi, Henri, 1966, et al.
(författare)
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Risk factors for the development of albuminuria and renal impairment in type 2 diabetes—the Swedish National Diabetes Register (NDR)
- 2010
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Ingår i: Nephrology, Dialysis and Transplantation. - : Oxford University Press (OUP). - 0931-0509 .- 1460-2385. ; 26:4, s. 1236-1243
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Tidskriftsartikel (refereegranskat)abstract
- Background. The aim of this study was to identify clinical risk factors associated with the development of albuminuria and renal impairment in patients with type 2 diabetes (T2D). In addition, we evaluated if different equations to estimate renal function had an impact on interpretation of data. This was done in a nationwide population-based study using data from the Swedish National Diabetes Register. Methods. Three thousand and six hundred sixty-seven patients with T2D aged 30-74 years with no signs of renal dysfunction at baseline (no albuminuria and eGFR >60 mL/min/1.73 m(2) according to MDRD) were followed up for 5 years (2002-2007). Renal outcomes, development of albuminuria and/or renal impairment [eGFR < 60 mL/min/1.73 m(2) by MDRD or eCrCl > 60 mL/min by Cockgroft-Gault (C-G)] were assessed at follow-up. Univariate regression analyses and stepwise regression models were used to identify significant clinical risk factors for renal outcomes. Results. Twenty percent of patients developed albuminuria, and 11% renal impairment; thus, ~6-7% of all patients developed non-albuminuric renal impairment. Development of albuminuria or renal impairment was independently associated with high age (all P < 0.001), high systolic BP (all P < 0.02) and elevated triglycerides (all P < 0.02). Additional independent risk factors for albuminuria were high BMI (P < 0.01), high HbA1c (P < 0.001), smoking (P < 0.001), HDL (P < 0.05) and male sex (P < 0.001), and for renal impairment elevated plasma creatinine at baseline and female sex (both P < 0.001). High BMI was an independent risk factor for renal impairment when defined by MDRD (P < 0.01), but low BMI was when defined by C-G (P < 0.001). Adverse effects of BMI on HbA1c, blood pressure and lipids accounted for ~50% of the increase risk for albuminuria, and for 41% of the increased risk for renal impairment (MDRD). Conclusions. Distinct sets of risk factors were associated with the development of albuminuria and renal impairment consistent with the concept that they are not entirely linked in patients with type 2 diabetes. Obesity and serum triglycerides are semi-novel risk factors for development of renal dysfunction and BMI accounted for a substantial proportion of the increased risk. The equations used to estimate renal function (MDRD vs. C-G) had an impact on interpretation of data, especially with regard to body composition and gender.
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| 5. |
- Afghahi, Henri, 1966, et al.
(författare)
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The association between long-term glycemic control and all-cause mortality is different among older versus younger patients with diabetes mellitus and maintenance hemodialysis treatment.
- 2022
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Ingår i: Diabetes research and clinical practice. - : Elsevier BV. - 1872-8227 .- 0168-8227. ; 191
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Tidskriftsartikel (refereegranskat)abstract
- Knowledge about association between glycated hemoglobin (HbA1c) and risk of all-cause mortality in patients with diabetes mellitus on maintenance hemodialysis (HD)-treatment is sparse. The study aims to investigate association between HbA1c and all-cause mortality in patients with diabetes and maintenance HD-treatment, separately for two age groups- above and below 75years.2487 patients (mean age 66years, 66% men) were separated in two age groups: ≤75years (n=1810) and>75years (n=677) and followed up between 2008 and 2018. Hazard ratios (HR) and 95% confidence intervals (CI) for associations between HbA1c and all-cause mortality were calculated using Cox-regression-models.1295 (52%) patients died and 473 (70%) among the patients above 75years old. In the multivariate analysis, HbA1c5-6% was used as reference. In patients≤75years old, only increased HbA1c>9.7%, HR2.03(CI1.43-2.89) was associated with increased risk of all-cause mortality. In patients>75years, HbA1c≤5%, HR1.67(CI1.16-2.40); HbA1c6.9-7.8%, HR1.41(CI1.03-1.93) and HbA1c8.7-9.7%, HR1.79 (CI1.08-2.96) were associated with increased risk of all-cause mortality.We found a J-shaped association between HbA1c and mortality only in diabetic HD-patients>75years. This probably indicates that in an old population of diabetic HD-patients, both intensive glucose control and hyperglycemia could be harmful and associated with higher risk of death.
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| 6. |
- Nasic, Salmir, et al.
(författare)
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Changes in Numbers of Glomerular Macrophages Between Two Consecutive Biopsies and the Association With Renal Transplant Graft Survival.
- 2024
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Ingår i: Clinical transplantation. - : John Wiley & Sons. - 1399-0012 .- 0902-0063. ; 38:7
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Tidskriftsartikel (refereegranskat)abstract
- Macrophages are involved in kidney transplants. The aim of the study was to investigate if changes exist in the levels of glomerular macrophage index (GMI) between two consecutive kidney transplant biopsies, and if so to determine their potential impact on graft survival.Two consecutive biopsies were performed on the same renal graft in 623 patients. GMI was categorized into three GMI classes: ≤1.8 Low, 1.9-4.5 Medium, and ≥4.6 High. This division yielded nine possible switches between the first and second biopsies (Low-Low, Low-Medium, etc.). Cox-regressions were used and hazard ratios (HR) with 95% confidence interval (CI) are presented.The worst graft survival was observed in the High-High group, and the best graft survival was observed in the Low-Low and High-Low groups. Compared to the High-High group, a reduction of risk was observed in nearly all other decreasing groups (reductions between 65% and 80% of graft loss). After adjustment for covariates, the risk for graft-loss was lower in the Low-Low (HR = 0.24, CI 0.13-0.46), Low-Medium (HR = 0.25, CI 0.11-0.55), Medium-Low (HR = 0.29, CI 0.11-0.77), and the High-Low GMI (HR = 0.31, CI 0.10-0.98) groups compared to the High-High group as the reference.GMI may change dynamically, and the latest finding is of most prognostic importance. GMI should be considered in all evaluations of biopsy findings since high or increasing GMI levels are associated with shorter graft survival. Future studies need to consider therapeutic strategies to lower or maintain a low GMI. A high GMI besides a vague histological finding should be considered as a warning sign requiring more frequent clinical follow up.
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| 7. |
- Nasic, Salmir, et al.
(författare)
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Sex-specific time trends of long-term graft survival after kidney transplantation : a registry-based study
- 2023
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Ingår i: Renal failure. - : Taylor & Francis. - 0886-022X .- 1525-6049. ; 45:2
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Tidskriftsartikel (refereegranskat)abstract
- Background: Sex-specific trends over time with respect to kidney graft survival have scarcely been described in earlier studies. The present study aimed to examine whether kidney graft survival differs between women and men over time.Methods: This study was based on prospectively collected data extracted from a quality registry including all kidney transplant patients between January 1965 and September 2017 at the transplantation center of a university hospital in Sweden. The transplantation center serves a population of approximately 3.5 million inhabitants. Only the first graft for each patient was included in the study resulting in 4698 transplantations from unique patients (37% women, 63% men). Patients were followed-up until graft failure, death, or the end of the study. Death-censored graft survival analysis after kidney transplantation (KT) was performed using Kaplan-Meier analysis with log-rank test, and analysis adjusted for confounders was performed using multivariable Cox regression analysis.Results: Median age at transplantation was 48 years (quartiles 36–57 years) and was similar for women and men. Graft survival was analyzed separately in four transplantation periods that represented various immunosuppressive regimes (1965-1985, 1986–1995, 1996–2005, and 2006–2017). Sex differences in graft survival varied over time (sex-by-period interaction, p = 0.026). During the three first periods, there were no significant sex differences in graft survival. However, during the last period, women had shorter graft survival (p = 0.022, hazard ratio (HR) 1.71, 95% confidence interval (CI) 1.1–2.7, adjusted for covariates). Biopsy-proven rejections were more common in women.Conclusions: In this registry-based study, women had shorter graft survival than men during the last observation period (years 2006–2017).
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| 8. |
- Nasic, Salmir, et al.
(författare)
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Sex-specific time trends of long-term graft survival after kidney transplantation - a registry-based study
- 2023
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Ingår i: Renal Failure. - 0886-022X. ; 45:2
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Tidskriftsartikel (refereegranskat)abstract
- Background Sex-specific trends over time with respect to kidney graft survival have scarcely been described in earlier studies. The present study aimed to examine whether kidney graft survival differs between women and men over time.Methods This study was based on prospectively collected data extracted from a quality registry including all kidney transplant patients between January 1965 and September 2017 at the transplantation center of a university hospital in Sweden. The transplantation center serves a population of approximately 3.5 million inhabitants. Only the first graft for each patient was included in the study resulting in 4698 transplantations from unique patients (37% women, 63% men). Patients were followed-up until graft failure, death, or the end of the study. Death-censored graft survival analysis after kidney transplantation (KT) was performed using Kaplan-Meier analysis with log-rank test, and analysis adjusted for confounders was performed using multivariable Cox regression analysis.Results Median age at transplantation was 48 years (quartiles 36-57 years) and was similar for women and men. Graft survival was analyzed separately in four transplantation periods that represented various immunosuppressive regimes (1965-1985, 1986-1995, 1996-2005, and 2006-2017). Sex differences in graft survival varied over time (sex-by-period interaction, p = 0.026). During the three first periods, there were no significant sex differences in graft survival. However, during the last period, women had shorter graft survival (p = 0.022, hazard ratio (HR) 1.71, 95% confidence interval (CI) 1.1-2.7, adjusted for covariates). Biopsy-proven rejections were more common in women.Conclusions In this registry-based study, women had shorter graft survival than men during the last observation period (years 2006-2017).
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| 10. |
- Peters, Björn, et al.
(författare)
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Risk factors for biopsy complications in initial versus subsequent biopsies in native and transplant kidneys.
- 2021
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Ingår i: Acta radiologica. - : SAGE Publications. - 1600-0455 .- 0284-1851. ; 62:10, s. 1426-1432
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Tidskriftsartikel (refereegranskat)abstract
- Few studies exist about risk factors for complications in subsequent biopsies.To explore risk factors for complications in initial versus subsequent biopsies in native and transplant kidneys, which may predict biopsy complications.In a multicenter study, 2830 native kidney biopsies (4.3% subsequent) were analyzed for major complications (1251 of these were also analyzed for minor) and 667 transplant kidney biopsies (29% subsequent) were analyzed for major and minor complications. No death or nephrectomy were described. Fisher's exact test, Student's t-test, chi-square analyses, and univariate and multiple binary logistic regression analyses were employed; P<0.05 was considered significant.In initial native kidney biopsies, the frequency of major complications was higher in women compared to men (odds ratio 1.6, 95% confidence interval 1.1-2.2), in younger patients (50 vs. 54 years, P=0.007), and in patients with lower weight (78 vs. 82 kg, P=0.005). In subsequent native kidney biopsies, patients with major complications had a higher systolic blood pressure (145 vs. 132mmHg, P=0.03). In initial transplant kidney biopsies, biopsies with major complications had less glomeruli in the biopsy (17 vs. 24, P=0.046). In subsequent transplant kidney biopsies, patients with major complications had a higher mean arterial pressure (112 vs. 98mmHg, P=0.002). In subsequent native kidney biopsies, there was a higher number of SLE-nephritis (12% vs. 4.6%, P=0.001) compared to initial biopsies.The different types of risk factors for complications in initial versus subsequent renal biopsies could be important for the clinicians to improve patients' safety.
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| 11. |
- Svensson, Maria K., et al.
(författare)
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Decreased systolic blood pressure is associated with increased risk of all-cause mortality in patients with type 2 diabetes and renal impairment : A nationwide longitudinal observational study of 27,732 patients based on the Swedish National Diabetes Register
- 2017
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Ingår i: Diabetes & Vascular Disease Research. - : SAGE PUBLICATIONS LTD. - 1479-1641 .- 1752-8984. ; 14:3, s. 226-235
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Tidskriftsartikel (refereegranskat)abstract
- Background: Previous studies have shown a U-shaped relationship between systolic blood pressure and risk of all-cause of mortality in patients with type 2 diabetes and renal impairment.Aims: To evaluate the associations between time-updated systolic blood pressure and time-updated change in systolic blood pressure during the follow-up period and risk of all-cause mortality in patients with type 2 diabetes and renal impairment.Patients and methods: A total of 27,732 patients with type 2 diabetes and renal impairment in the Swedish National Diabetes Register were followed for 4.7years. Time-dependent Cox models were used to estimate risk of all-cause mortality. Time-updated mean systolic blood pressure is the average of the baseline and the reported post-baseline systolic blood pressures.Results: A time-updated systolic blood pressure<130mmHg was associated with a higher risk of all-cause mortality in patients both with and without a history of chronic heart failure (hazard ratio: 1.25, 95% confidence interval: 1.13-1.40 and hazard ratio: 1.26, 1.17-1.36, respectively). A time-updated decrease in systolic blood pressure>10mmHg between the last two observations was associated with higher risk of all-cause mortality (-10 to -25mmHg; hazard ratio: 1.24, 95% confidence interval: 1.17-1.32).Conclusion: Both low systolic blood pressure and a decrease in systolic blood pressure during the follow-up are associated with a higher risk of all-cause mortality in patients with type 2 diabetes and renal impairment.
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