The aftermath of coronavirus disease of 2019: devastation or a new dawn for nephrology?

The acute crisis with the coronavirus disease of 2019 (COVID-19) caused by the novel coronavirus Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-COV-2) is the largest biomedical catastrophe of our lifetimes. Like so many other disasters in the past, such as war, famine, social unrest and economic calamities, this too shall pass, but it will undoubtedly leave the world changed. Some of the changes are already evident, but some are inevitable once we get over this pandemic. In this perspective, I provide examples of how the virus is already inducing change in the practice of medicine at large and for nephrology in particular. As is true for many changes, some persist after the emergency is over, so I speculate on how nephrology may change once we surmount this predicament (Figure 1)

Minimally sufficient numbers of measurements for validation of 24-hour blood pressure monitoring in chronic kidney disease

Ambulatory blood pressure monitoring (ABPM) remains a reference standard, but the minimal number of ABPM readings required to diagnose hypertension has not been empirically validated. Among 360 patients with chronic kidney disease and 38 healthy controls, 24-hour blood pressure was recorded 2 times per hour during the night and 3 times per hour during the day. All subjects had at least 90% of the expected readings recorded. From this full set of ABPM recordings, we selected variable numbers of measurements and compared the performance of the selected readings against that of the full sample under either random or sequential sampling schemes. With 8 randomly selected systolic blood pressure readings, we were able to make diagnostic decisions in concordance with that from the full ABPM sample 91.0% of the time (kappa 0.804). With 15 randomly selected diastolic blood pressure readings, we made concordant decisions 96.3% of the time (kappa 0.810). A serial selection scheme generally required a greater number of readings to achieve the same levels of concordance with the full ABPM data. With a random selection scheme, 26 readings provided 95% confidence that the sample mean will be within 5 mm Hg of the true systolic blood pressure mean, and within 3.5 mm Hg of the true diastolic blood pressure mean

Treating hypertension in hemodialysis improves symptoms seemingly unrelated to volume excess

BACKGROUND: Among hemodialysis patients, probing dry weight is an effective strategy for improving control of hypertension. Whether controlling hypertension improves or worsens symptoms among such patients remains unclear. The purpose of the study was to develop a tool to evaluate symptoms and examine the relationship of the change in these symptoms with blood pressure (BP) control. METHODS: Among patients participating in the Hemodialysis Patients Treated with Atenolol or Lisinopril (HDPAL) randomized controlled trial, a confirmatory factor analysis (CFA) was performed to establish the relationship between symptoms and organ systems. Next, the change in symptom scores pertaining to organ systems was analyzed using a mixed model. Finally, the independent effect of lowering home BP on change in symptoms was evaluated. RESULTS: Among 133 participants where symptoms were available at baseline, CFA revealed four level 1 domains: gastrointestinal symptoms, dialysis-related symptoms, cardiovascular symptoms and general symptoms. All except dialysis-related symptoms were ascribed to uremia (level 2 domain). Uremic symptoms improved over 6 months and then increased. Dialysis-related symptoms (fatigue, cramps and orthostatic dizziness) did not worsen despite lowering home BP. Probing dry weight was independently associated with an improvement in cardiovascular symptoms such as shortness of breath. CONCLUSIONS: Reducing BP through the use of a strategy that includes volume control and medication improves symptoms seemingly unrelated to volume excess. In long-term hemodialysis patients, treating hypertension using home BP measurements may improve well-being

Defining end-stage renal disease in clinical trials: a framework for adjudication

Unlike definition of stroke and myocardial infarction, there is no uniformly agreed upon definition to adjudicate end-stage renal disease (ESRD). ESRD remains the most unambiguous and clinically relevant end point for clinical trialists, regulators, payers and patients with chronic kidney disease. The prescription of dialysis to patients with advanced chronic kidney disease is subjective and great variations exist among physicians and countries. Given the difficulties in diagnosing ESRD, the presence of estimated GFR <15 mL/min/1.7 3m2 itself has been suggested as an end point. However, this definition is still a surrogate since many patients may live years without being symptomatic or needing dialysis. The purpose of this report is to describe a framework to define when the kidney function ends and when ESRD can be adjudicated. Discussed in this report are (i) the importance of diagnosing symptomatic uremia or advanced asymptomatic uremia thus establishing the need for dialysis; (ii) establishing the chronicity of dialysis so as to distinguish it from acute dialysis; (iii) establishing ESRD when dialysis is unavailable, refused or considered futile and (iv) the adjudication process. Several challenges and ambiguities that emerge in clinical trials and their possible solutions are provided. The criteria proposed herein may help to standardize the definition of ESRD and reduce the variability in adjudicating the most important renal end point in clinical trials of chronic kidney disease

Arterial stiffness and its relationship to clinic and ambulatory blood pressure: a longitudinal study in non-dialysis chronic kidney disease

Background Both arterial stiffness and systolic blood pressure (BP) are established cardiovascular risk factors, yet little is known about their interrelationship in chronic kidney disease (CKD). The goal of this prospective study was to describe the trajectory of aortic pulse wave velocity (PWV) and BP and to compare the longitudinal interrelationship of BP (clinic and 24 h ambulatory recording) with the PWV. Methods Clinic BP was taken in two ways: at the time of the measurement of the PWV (Clinic-S) and as an average of triplicate measurements on three separate occasions within 1 week (Clinic-M). 24 h ambulatory BP was measured using a validated monitor and PWV was measured in the aorta using an echo-Doppler technique. Results Among 255 veterans with CKD followed for over up to 4 years, the rate of change of log PWV was inversely related to the baseline PWV; the trajectories were variable among individuals and the net population change was no different from zero. In contrast, systolic BP significantly increased, but linearly, and a strong relationship was seen between cross-sectional and longitudinal changes in Clinic-M systolic BP and log PWV. In contrast, a longitudinal relationship between Clinic-S and log PWV was absent. In the case of 24-h ambulatory BP, a strong cross-sectional change was seen between awake and 24 h systolic BP but not between sleep BP and log PWV Conclusion In conclusion, among people with CKD, the PWV changes over time and is inversely related to the baseline PWV. An average of clinic BP measurements taken over three visits, but not single measurements, are useful to assess the PWV and its change over time. Differences exist between ambulatory BP monitoring recording during the sleep and awake states in their ability to predict the PWV. Taken together, these data support the view that among those with CKD not on dialysis, targeting clinic BP taken on multiple occasions using a standardized methodology or daytime ambulatory systolic BP may slow the progression of arterial damage

Albuminuria and masked uncontrolled hypertension in chronic kidney disease

Background Masked uncontrolled hypertension (MUCH) is associated with greater target organ damage such as left ventricular hypertrophy, increased arterial stiffness and albuminuria. Whether MUCH independently associates with greater cardiovascular end-organ damage or kidney damage is unclear. The objective of this study was to assess the strength of the relationship of MUCH (awake ambulatory blood pressure ≥135/85 mmHg and clinic blood pressure <140/90 mmHg) with target organ damage. Methods In a cross-sectional study at a veterans' administration medical center, clinically normotensive veterans without chronic kidney disease (CKD) (n = 29) and 287 patients with CKD and controlled hypertension (CH, n = 193), MUCH (n = 67) and uncontrolled hypertension (UCH, n = 27) had evaluation of target organ damage. Target organ damage was measured by echocardiography [left ventricular mass index (LVMI)], arterial ultrasonography [aortic pulse wave velocity (PWV)] and 24-h urine collection [albuminuria (urine albumin to creatinine ratio)] in all participants. Results Compared to that of controls, LVMI was higher by 21.8 g/m2 (CI, 4.0–39.7 g/m2) in CH, 27.9 (CI, 8–47.8) in MUCH and 39.5 (CI, 15.7–63.2) in UCH (P < 0.01 for group differences, P < 0.01 for linear trend). Although differences persisted after adjustment for age, sex and race, they lost significance after adjustments for cardiovascular risk factors and their treatment. Compared to that of controls, PWV was different among CH, MUCH and UCH (P = 0.04 for group differences, P = 0.02 for linear trend). However, differences lost significance after adjustments for age, sex and race. Compared to that of controls, log2 UACR was higher by 2.40 mg/mg (CI, 1.28–3.52) in CH, 4.94 (CI, 3.70–6.18) in MUCH and 6.01 (CI, 4.49–7.53) in UCH (P < 0.0001 for group difference, P < 0.0001 for linear trend). Differences persisted after adjustment for age, sex and race, cardiovascular risk factors and their treatment and cardiovascular disease (P < 0.0001 for group difference, P < 0.0001 for linear trend). Conclusions MUCH is more strongly related to albuminuria compared with cardiovascular damage as assessed by left ventricular mass and PWV. A graded and an independent relationship of blood pressure classification status with albuminuria is consistent with the hypothesis that renal mechanisms may be more important than cardiovascular disease in mediating the pathogenesis of MUCH

Iron deficiency anemia in chronic kidney disease: Uncertainties and cautions

Anemia in chronic kidney disease is common and iron deficiency is an important cause. To repair iron-deficiency anemia, replacement of iron is needed. Iron can be replaced either by the oral route or by the intravenous route. In a meta-analysis, 5 of the 6 trials were short-term, 1 to 3 months, and compared to oral iron, the mean increase in hemoglobin with intravenous iron was only 0.31 g/dL. However, one of the studies included in this meta-analysis was 6 months long and had a mean decline in hemoglobin of 0.52 g/dL associated with intravenous iron administration. Given the short duration of most of the clinical trials comparing oral with intravenous administration of iron the long-term safety of these modes of administration of supplemental iron could not be assessed. Replacement of iron by the oral route is associated with mostly minor complications such as black stools, constipation, and abdominal discomfort. In contrast, intravenous administration of iron may lead to severe adverse events such as anaphylaxis and, as a more recent randomized trial has suggested, delayed complications such as infections and cardiovascular disease. Delayed complications of repeated intravenous iron use are difficult to recognize at an individual level therefore inpatients who have had recent cardiovascular events or are infected, intravenous iron should probably be avoided. Balancing safety and efficacy would require clinical judgment because 1 size may not fit all till we have better data to support the liberal use of parenteral iron