A Urine pH-Ammonium Acid/Base Score and CKD Progression.

INTRODUCTION: Acidosis is associated with exacerbated loss of kidney function in chronic kidney disease (CKD). Currently, acid/base status is assessed by plasma measures, although organ-damaging covert acidosis, subclinical acidosis, may be present before reflected in plasma. Low urine NH4+ excretion associates with poor kidney outcomes in CKD and is proposed as a marker for subclinical acidosis. However, low NH4+ excretion could result from either a low capacity or a low demand for acid excretion. We hypothesized that a urine acid/base-score reflecting both the demand and capacity for acid excretion would better predict CKD progression. METHODS: 24-hour urine collections were included from three clinical studies of patients with CKD stage 3 and 4: A development cohort (n=82), a variation cohort (n=58), and a validation cohort (n=73). A urine acid/base-score was derived and calculated from urinary pH and [NH4+]. Subclinical acidosis was defined as an acid/base-score below the lower limit of the 95% prediction interval of healthy controls. Main outcomes were change in measured GFR after 18 months and CKD progression (defined as ≥50% decline in eGFR, initiation of long-term dialysis or kidney transplantation) during up to 10 years of follow-up. RESULTS: Subclinical acidosis was prevalent in all cohorts (n=54/82, 48/73, and 40/58, ∼67%). Subclinical acidosis was associated with an 18% (95% CI: 2-32) larger decrease of measured GFR after 18 months. During a median follow-up of 6 years, subclinical acidosis was associated with a markedly higher risk for CKD progression. Adjusted hazard ratios were 9.88 (95% CI 1.27-76.7) in the development cohort and 11.1 in the validation cohort (95% CI: 2.88-42.5). The acid/base-score had a higher predictive value for CKD progression than NH4+ excretion alone. CONCLUSIONS: Subclinical acidosis, defined by a new urine acid/base-score, was associated with a higher risk of CKD progression in patients with CKD stage 3 and 4.

Prediction of CKD Progression and Cardiovascular Events Using Albuminuria and Pulse Wave Velocity.

INTRODUCTION: Chronic kidney disease (CKD) is associated with cardiovascular disease (CVD) and death. Albuminuria is an established risk factor, but additional biomarkers predicting CKD progression or CVD are needed. Arterial stiffness is an easily measurable parameter that has been associated with CVD and mortality. We evaluated the ability of carotid-femoral pulse wave velocity (PWV) and urine albumin-creatinine (UAC) ratio to predict CKD progression, cardiovascular events, and mortality in a cohort of CKD patients. METHODS: In CKD stage 3-5 patients, PWV and UAC were measured at baseline. CKD progression was defined as 50% decline in estimated glomerular filtration rate (eGFR), initiation of dialysis, or renal transplantation. A composite endpoint was defined as CKD progression, myocardial infarction, stroke, or death. Endpoints were analyzed using Cox regression analysis adjusted for possible confounders. RESULTS: We included 181 patients (median age 69 [interquartile range 60-75] years, 67% males) with a mean eGFR of 37 ± 12 mL/min/1.73 m2 and UAC 52 (5-472) mg/g. Mean PWV was 10.6 m/s. Median follow-up until first event was 4 (3-6) years with 44 and 89 patients reaching a CKD progression or composite endpoint, respectively. UAC (g/g) significantly predicted both CKD progression (HR 1.5 [1.2; 1.8]) and composite endpoints (HR 1.4 [1.1; 1.7]) in adjusted Cox regression. In contrast, PWV (m/s) was not associated with neither CKD progression (HR 0.99 [0.84; 1.18]) nor the composite endpoint (HR 1.03 [0.92; 1.15]). CONCLUSION: In an aging CKD population, UAC predicted both CKD progression and a composite endpoint of CKD progression, cardiovascular events, or death, while PWV did not.

Effects of enhanced versus reduced vasodilating treatment on brachial and central blood pressure in patients with chronic kidney disease: a randomized controlled trial.

BACKGROUND: Blood pressure (BP) control is important in chronic kidney disease (CKD), but a reduction in brachial BP may not mirror changes in central aortic BP (cBP) during antihypertensive medication. We hypothesize that a fall in cBP is better reflected during enhanced vasodilation treatment (EVT) compared with reduced vasodilation treatment (RVT) because of different hemodynamic actions of these interventions. METHODS: Eighty-one hypertensive CKD stage 3-4 patients (mean measured glomerular filtration rate 36 ml/min per 1.73 m2) were randomized to either EVT based on renin--angiotensin blockade and/or amlodipine or RVT based on nonvasodilating ß-blockade (metoprolol). Before randomization and following 18 months of treatment, we performed 24-h ambulatory BP measurements (ABPM) and radial artery pulse wave analysis for estimation of cBP and augmentation index (AIx). Forearm resistance (Rrest) was determined by venous occlusion plethysmography and arterial stiffness by carotid--femoral pulse wave velocity (PWV). Matched healthy controls were studied once for comparison. RESULTS: Compared with controls, CKD patients had elevated ABPM, cBP and PWV. Although ABPM remained unchanged from baseline to follow-up in both treatment groups, cBP decreased 4.7/2.9 mmHg (systolic/diastolic) during EVT and increased 5.1/1.5 mmHg during RVT (Δ=9.8/4.4 mmHg, P=0.02 for SBP, P = 0.05 for DBP). At follow-up, the difference between systolic cBP and 24-h ABPM (ΔBPsyst) was negatively associated with heart rate and positively associated with AIx and Rrest (all P < 0.01) but not PWV (P = 0.32). CONCLUSION: In CKD patients, EVT and RVT have opposite effects on cBP and the difference between cBP and ambulatory BP is larger for EVT than RVT.

Patient selection for islet or solid organ pancreas transplantation: experiences from a multidisciplinary outpatient-clinic approach.

OBJECTIVE: ß-cell replacement therapy (ßCRT), including pancreas transplantation alone (PTA) and islet transplantation (ITX), is a treatment option for selected type 1 diabetes patients. All potential candidates for ßCRT in Norway are referred to one national transplant centre for evaluation before any pre-transplant workup is started. This evaluation was performed by a transplant nephrologist alone prior to 2015 and by a multidisciplinary team (MDT) from 2015. We have reviewed the allocation of patients to treatment modality and the 1-year clinical outcome for the patients after transplantation. RESEARCH DESIGN AND METHODS: Medical charts of all patients evaluated for ßCRT between 2010 and 2020 in Norway were retrospectively analysed and the outcome of patients receiving ßCRT were studied. RESULTS: One hundred and forty-four patients were assessed for ßCRT eligibility between 2010 and 2020. After MDT evaluation was introduced for ßCRT eligibility in 2015, the percentage of referred patients accepted for the transplant waiting list fell from 84% to 40% (P < 0.005). One year after transplantation, 73% of the PTA and none of the ITX patients were independent of exogenous insulin, 8% of the PTA and 90% of the ITX patients had partial graft function while 19% of the PTA and 10% of the ITX patients suffered from graft loss. CONCLUSION: The acceptance rate for ßCRT was significantly reduced during a 10-year observation period and 81% of the PTA and 90% of the ITX patients had partial or normal graft function 1 year post-transplant.

Aortic Calcification Affects Noninvasive Estimates of Central Blood Pressure in Patients with Severe Chronic Kidney Disease.

BACKGROUND: Central blood pressure (BP) assessed noninvasively considerably underestimates true invasively measured aortic BP in chronic kidney disease (CKD) patients. The difference between the estimated and the true aortic BP increases with decreasing estimated glomerular filtration rates (eGFR). The present study investigated whether aortic calcification affects noninvasive estimates of central BP. METHODS: Twenty-four patients with CKD stage 4-5 undergoing coronary angiography and an aortic computed tomography scan were included (63% males, age [mean ± SD ] 53 ± 11 years, and eGFR 9 ± 5 mL/min/1.73 m2). Invasive aortic BP was measured through the angiography catheter, while non-invasive central BP was obtained using radial artery tonometry with a SphygmoCor® device. The Agatston calcium score (CS) in the aorta was quantified on CT scans using the CS on CT scans. RESULTS: The invasive aortic systolic BP (SBP) was 152 ± 23 mm Hg, while the estimated central SBP was 133 ± 20 mm Hg. Ten patients had a CS of 0 in the aorta, while 14 patients had a CS >0 in the aorta. The estimated central SBP was lower than the invasive aortic SBP in patients with aortic calcification compared to patients without (mean difference 8 mm Hg, 95% CI 0.3-16; p = 0.04). The brachial SBP was lower than the aortic SBP in patients with aortic calcification compared to patients without (mean difference 10 mm Hg, 95% CI 2-19; p = 0.02). CONCLUSION: In patients with advanced CKD the presence of aortic calcification is associated with a higher difference between invasively measured central aortic BP and non-invasive estimates of central BP as compared to patients without calcifications.

Early gestational age at preeclampsia onset is associated with subclinical atherosclerosis 12 years after delivery.

INTRODUCTION: Women with a history of preeclampsia have increased risk of cardiovascular disease later in life. However, it is unclear whether early gestational age at preeclampsia onset is associated with higher cardiovascular disease risk. This study aimed to test the association between gestational age at preeclampsia onset (including the early-onset/late-onset preeclampsia distinction) and subclinical atherosclerosis and arterial stiffness in age-matched women 12 years after index pregnancy. MATERIAL AND METHODS: Eligible participants were identified in two Danish registries. Main outcome measures were carotid plaque presence, carotid intima-media thickness, aortic pulse wave velocity, and augmentation index adjusted for heart rate. RESULTS: Twenty-four women with previous early-onset preeclampsia, 24 with previous late-onset preeclampsia and 24 with previous normotensive pregnancies were included after matching on age (±2 years) and time since delivery (±1 year). In all outcome measures, the early-onset group had the highest percentage or mean value. In the adjusted analysis, the early-onset group significantly differed from the late-onset group in all outcome measures except aortic pulse wave velocity. The early-onset group also had significantly higher carotid intima-media thickness (average and left) compared with the normotensive group. Gestational age at preeclampsia onset as a continuous variable was significantly associated to both carotid plaque presence and carotid intima-media thickness (average and right). CONCLUSIONS: Gestational age at preeclampsia onset is negatively associated with markers of subclinical atherosclerosis 12 years after delivery. Potentially, gestational age at preeclampsia onset might be helpful in directing cardiovascular disease prevention after preeclampsia.