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Background and Aims Hypertension resistant to drug treatment is common among CKD patients. However, the phenotype of resistant hypertension in the CKD population is still loosely defined and scarcely characterized. Method In a cohort of 759 stage 2-5 CKD patients, we identified a subgroup of 647 patients with >4 longitudinal visits (range 4-7 visits) over a median follow-up time of 36 months. These patients did not differ from the original study population as for age (62±11 years vs 62±11), gender (59% vs 60%), diabetes (34% vs 35%) and eGFR (36±13 versus 36±13 ml/min/1.73m2). We adopted a conservative definition of resistant hypertension i.e. as a BP above the 2020 KDIGO guideline threshold (130/80 mmHg) in spite of concurrent use of 3 antihypertensive agents (at maximum tolerated doses) of different classes including a diuretic or BP controlled with four or more medications in at least 75% of visits. Adherence to drug treatment in this cohort was systematically checked by attending physicians across all visits. Data are given as mean ± SD or as median and interquartile range (IQR). Results Across the 36 months follow-up, 131 out of 647 patients (20%) had resistant hypertension in >75% of visits. Resistant hypertensive patients were older (64±8 years vs 61±11), more frequently diabetics (53% vs 29%) and with background cardiovascular comorbidities (38% vs 29%) , higher body mass index (BMI) (30±5 kg/m2 vs 28±4 kg/m2), serum phosphate (3.9±0.7 mg/dL vs 3.7±0.8 mg/dL), CRP (median: 3.2 mg/L, IQR: 1.6-6.5 vs 3.2 mg/L, IQR: 1.6-6.5 vs 2.1 mg/L, 0.9-5.1 mg/L), 24h urinary protein (median: 1.0 g/24h, IQR: 0.4-2.3 vs median: 0.5 g/24h, IQR: 0.2-1.0 g/24h) and lower serum albumin (4.1±0.5 g/dL vs 4.2±0.5 g/dL) and eGFR (34±13 ml/min/1.73m2 vs 37±14 ml/min/1.73m2 as compared to remaining patients (all P Conclusion A rigorously defined phenotype of resistant hypertension has a 20% prevalence in the CKD population. Proteinuria, high BMI and obesity are the main risk factors associated with this phenotype. Optimization of diabetes control, weight loss and pharmacotherapy targeting proteinuria may mitigate resistant hypertension in the CKD population.

Background Sleep‐disordered breathing ( SDB ) is considered a strong risk factor for hypertension in the general population. This disturbance is common in end‐stage kidney disease patients on long‐term hemodialysis and improves early on after renal transplantation. Whether SDB may be a risk factor for hypertension in renal transplant patients is unclear. Methods and Results We investigated the long‐term evolution of simultaneous polysomnographic and 24‐hour ambulatory blood pressure (BP) monitoring recordings in a cohort of 221 renal transplant patients. Overall, 404 paired recordings were made over a median follow‐up of 35 months. A longitudinal data analysis was performed by the mixed linear model. The apnea‐hypopnea index increased from a median baseline value of 1.8 (interquartile range, 0.6–5.0) to a median final value of 3.6 (interquartile range, 1.7–10.4; P =0.009). Repeated categorical measurements of the apnea‐hypopnea index were directly associated with simultaneous 24‐hour, daytime, and nighttime systolic ambulatory BP monitoring (adjusted analyses; P ranging from 0.002–0.01). In a sensitivity analysis restricted to 139 patients with at least 2 visits, 24‐hour, daytime, and nighttime systolic BP significantly increased across visits ( P SDB (n=40), whereas the same BP metrics did not change in patients (n=99) with stable apnea‐hypopnea index. Conclusions In renal transplant patients, worsening SDB associates with a parallel increase in average 24‐hour, daytime, and nighttime systolic BP . These data are compatible with the hypothesis that the link between SDB and hypertension is causal in nature. Clinical trials are, however, needed to definitively test this hypothesis.

Background and Aims Measuring QoL in CKD patients is fundamental to estimate the human cost of chronic diseases and to assess the effect of treatments. Non-medical factors play an important role in CKD progression and QoL. However, there is very limited information on the evolution of QoL over time in CKD patients and it remains unclear whether traditional and CKD specific risk factors are implicated QoL in CKD patients over CKD progression. Method We studied a cohort of 582 stage 2-5 CKD patients (age: 61±12 years; M: 60%, diabetics: 33%) and measured QoL by the short form of the Rand corporation questionnaire (SF36), an instrument which measures eight domains of QoL (physical functioning, role physical health, energy fatigue, pain, role emotional problem, emotional well-being, social function, and general health] and two summary scores, (the physical component score and the mental component score) which are calculated by a well validated algorithm (Taft C et al, 2001, Quality of life research). In all patients the SF36 was administered at enrolment and after one (489 patients), two (n=434) and three (n=287) years. The evolution of SF36 dimensions over-time and the predictors of SF36 changes were analyzed by the Linear Mixed Model (LMM). Results At baseline the median value of the Physical Component Score (PCS) was 43.7 (Interquartile range: 34.0-50.3) and the Mental Component Score (MCS) was 46.3 (37-52.9) and on average did not change over the 3 years follow up [median PCS at the 3rd year: . 46.3 (35.7-52.0), median MCS at the 3rd year 43 (33.6-50.6)]. On average the GFR at baseline was 36±13 ml/min/1.73 m2 and declined to 34±17 ml/min/1.73m2 at the 3rd year. On detailed longitudinal analysis by the LMM the PCS associated with the evolution of the GFR over time (beta=0.10; 95% CI from 0.06 to 0.13; P Conclusion The PCS and the MCS remain stable over the course of CKD but appear associated with the evolution of the GFR over time. Traditional and CKD specific risk factors substantially confound and/ or mediate these associations.

Background and Aims In the post-hoc analyses of the SUSTAIN and ASSURE trials (Kidney Blood Press Res. 2018;43:449-457), Apabetalone, an epigenetic modulator which lowers serum alkaline phosphatase (AlkPhos), stabilized the GFR in patients with cardiovascular disease and a GFR Method We investigated the relationship between AlkPhos and the risk for a combined renal end-point (30% GFR loss or dialysis/renal transplantation) in a cohort of 609 stage 3-5 CKD patients with an average GFR of 34.8±12.1ml/min/1.73 m2. Results Median AlkPhos levels were 91 IU/L (Interquartile range 71-117 IU/L) and in the vast majority of patients had values below 147 IU/L (the upper limit of the normal range). Over a median follow up of 3 years, two-hundred patients had the combined renal end-point. In an unadjusted analysis 1 ln increase in AlkPhos entailed a 49% risk excess for the renal end-point (HR: 1.49, 95% CI 1.11-2.01, P=0.008). Adjusting for traditional (age, gender, smoking, diabetes, total cholesterol, BMI, systolic BP, CV comorbidities) and CKD specific risk factors (hemoglobin, albumin, phosphate, and hs-CRP) did not modify the strength of this association (HR:1.48, 95% CI 1.08-2.02, P=0.016). Furthermore, In a fully adjusted analysis testing the GFR as an effect modifier of the AlkPhos - combined renal end point relationship showed a strong GFR- AlkPhos interaction (Figure). Indeed the risk for the combined renal end-point was gradually more pronounced at progressively more severe degrees of renal dysfunction, the HR being 0.94 (CI95% 0.60-1.47) at a GFR of 40 ml/min/m2 and 2.71 (CI95% 1.49-4.93) at 10 ml/min/1.73m2. Conclusion In patients with stage 3-5 CKD alkaline phosphatase within the normal range is associated with the risk for progression to ESRD and the GFR is an effect modifier of this relationship. Findings in this study are compatible with the hypothesis that within the normal range of this biomarker, the risk for CKD progression by alkaline phosphatase is amplified by the severity of CKD. These data are in keeping with post-hoc analyses of the SUSTAIN and ASSURE trials and provide circumstantial support to the hypothesis that interventions lowering serum alkaline phosphatase may mitigate CKD progression.

Background Adherence to low salt diets and control of hypertension remain unmet clinical needs in chronic kidney disease (CKD) patients. Methods We performed a 6-month multicentre randomized trial in non-compliant patients with CKD followed in nephrology clinics testing the effect of self-measurement of urinary chloride (69 patients) as compared with standard care (69 patients) on two primary outcome measures, adherence to a low sodium (Na) diet ( Results In the whole sample (N = 138), baseline UNa and 24-h ABPM were143 ± 64 mmol/24 h and 131 ± 18/72 ± 10 mmHg, respectively, and did not differ between the two study arms. Patients in the active arm of the trial used >80% of the chloride strips provided to them at the baseline visit and at follow-up visits. At the third month, UNa was 35 mmol/24 h (95% CI 10.8–58.8 mmol/24 h; P = 0.005) lower in the active arm than the control arm, whereas at 6 months the between-arms difference in UNa decreased and was no longer significant [23 mmol/24 h (95% CI −5.6–50.7); P = 0.11]. The 24-h ABPM changes as well as daytime and night-time BP changes at 3 and 6 months were similar in the two study arms (Month 3, P = 0.69–0.99; Month 6, P = 0.73–0.91). Office BP, the use of antihypertensive drugs, estimated Glomerular Filtration Rate (eGFR) and proteinuria remained unchanged across the trial. Conclusions The application of self-measurement of urinary chloride to guide adherence to a low salt diet had a modest effect on 24-h UNa and no significant effect on 24-h ABPM.

Lung congestion and frank pulmonary edema are established complications of acute kidney injury (AKI) and early detection and monitoring of lung congestion may be useful for the clinical management of AKI patients.We compared standardized clinical criteria (including lung crackles and peripheral edema grading) and simultaneous chest ultrasound (US) to detect lung congestion in a series of 39 inpatients with AKI.At baseline, twelve patients (31%) were clinically euvolemic and twelve presented clear-cur cardiovascular congestion (31%) by clinical criteria. Fifteen patients (38%) were hypovolemic. The median number of US-B lines in patients with cardiovascular congestion was much higher (50, inter-quartile range 27-99) than in euvolemic (14, IQR 11-37) and hypovolemic patients (7, IQR 3-16, P 0.001). Remarkably, a substantial proportion of asymptomatic euvolemic (66%) and hypovolemic (46%) patients had lung congestion of moderate to severe degree ( 15 US-B lines) by lung US. Crackles severity and the number of US-B lines over time were inter-related (Spearman's ρ = 0.38, P 0.01) but the agreement (Cohen k statistics) between the two metrics was unsatisfactory. Forty-eight percent of patients had lung congestion of moderate to severe degree by lung US and this estimate by far exceeded that by clinical criteria (32%).This pilot study shows that chest US has potential for the detection of lung congestion at a pre-clinical stage in AKI. The results of this pilot study form the basis for a clinical trial testing the usefulness of this technique for guiding lung congestion treatment in patients with AKI.

Background Excessive sodium intake is a risk factor for hypertension, cardiovascular disease and the risk for kidney failure in chronic kidney disease (CKD) patients. Methods We tested the diagnostic performance and the feasibility of an inexpensive method based on urine chloride strips for self-monitoring sodium intake in a series of 72 CKD patients. Results Twenty-four hour urinary chloride as measured by the reactive strips and 24 h urinary sodium were interrelated (r=0.59, p100 mmol/24 h, i.e. the upper limit recommended by current CKD guidelines. The strip method had 75.5% sensitivity and 82.6% specificity to correctly classify patients with urine sodium >100 mmol/24 h. The positive and the negative predictive values were 90.2% and 61.3%, respectively. The overall accuracy (ROC curve analysis) of urine chloride self-measurement for the >100 mmol/24 h sodium threshold was 87% (95% CI: 77%–97%). The large majority of patients (97%) perceived the test as useful to help compliance with the prescribed dietary sodium and considered the test as simple and of immediate application (58%) or feasible but requiring attention (39%). Conclusions A simple and inexpensive test for urine chloride measurement has a fairly good performance for the diagnosis of excessive sodium intake. The test is feasible and it is perceived by CKD patients as helpful for enhancing compliance to the dietary sodium recommendations. The usefulness of this test for improving hypertension control in CKD patients will be tested in a clinical trial (Clinicaltrials.gov RF-2010-2314890).

INTRODUCTION Hypertension remains a major problem in hemodialysis (HD) patients. METHODS We performed a pragmatic trial (Pragmatic Clinical Intervention on Blood Pressure Driven by Audit [CLINIDEA]) testing the effectiveness and safety of a 6-month multimodal intervention in hypertensive HD patients regarding the application of higher ultrafiltration (UF) rates or longer or more frequent dialyses in UF-intolerant patients, and an educational intervention to encourage patients to lower their salt and fluid intake. RESULTS Blood pressure (BP) in hypertensive patients (n=32) fell from 156.8 ± 13.3 / 81.1 ± 8.9 mm Hg to 147.9 ± 18.8 / 77.5 ± 11.1 mm Hg. UF intensification was well tolerated, and the BP goal was achieved without resorting to longer or more frequent dialyses. BP changes were paralleled by a consistent (p

An updated review of cases of reactivated visceral leishmaniasis (VL) in transplant patients is presented, with a new report of a kidney transplant patient who had VL caused by reactivation of a dormant infection contracted 21 years previously. Close to the time of disease reactivation, the patient had a primary varicella-zoster infection.

The plasma aldosterone concentration:renin ratio (ARR) is widely used for the screening of primary aldosteronism, but its reproducibility is unknown. We, therefore, investigated the within-patient reproducibility of the ARR in a prospective multicenter study of consecutive hypertensive patients referred to specialized centers for hypertension in Italy. After the patients were carefully prepared from the pharmacological standpoint, the ARR was determined at baseline in 1136 patients and repeated after, on average, 4 weeks in the patients who had initially an ARR ≥40 and in 1 of every 4 of those with an ARR r =0.69; P

Nephrosclerosis is usually diagnosed in patients with essential hypertension with no or mild proteinuria and no urinary abnormalities. Microalbuminuria is considered to be a marker of high risk for progressive renal disease in patients with diabetes mellitus but there is still no solid evidences that this alteration entails an adverse renal prognosis in essential hypertension. Independently of hypertension, nephrosclerosis is associated with endothelial dysfunction and evidence is accruing that genetic factors and a low number of nephrons at birth are important determinants of this disease.

The authors report the case of a 33-year-old Italian man who had three episodes of hypokalaemia with paralysis linked to hyperthyroidism. Because of its low prevalence in western populations, the diagnosis of thyrotoxic hypokalaemic periodic paralysis can be easily missed in non-Asian countries.