Onco-Hypertension in Patients with Kidney Disease.

BACKGROUND: Cancer, hypertension, and kidney disease are closely interrelated. Knowledge of the potential hypertensive and nephrotoxic effects of antineoplastic medications is critical to minimizing interruptions in cancer treatment. SUMMARY: Antineoplastic medications can cause hypertension, proteinuria, and kidney injury, often mediated by common mechanisms. Notably, inhibitors of the vascular endothelial growth factor pathway have the strongest association with both hypertension and proteinuria, typically acute in onset and often reversible after drug discontinuation. The abrupt rise in blood pressure can cause clinically significant hypertensive syndromes and contribute to overall morbidity. Significant proteinuria can herald kidney failure. Close monitoring of blood pressure and renal function during antineoplastic therapy and appropriate hypertension treatment are important. This article reviews available literature and proposes a step-by-step approach to manage cancer patients with concurrent hypertension and kidney disease. KEY MESSAGES: For antineoplastic medications with known hypertensive effect, blood pressure should be checked at baseline and serially during cancer treatment. Hypertensive crisis with end-organ damage, significant proteinuria, microscopic hematuria, or unexplained acute kidney injury necessitates drug cessation until further evaluation and resolution. In patients with chronic kidney disease and cancer therapy-related hypertension, angiotensin-converting enzyme inhibitor or angiotensin receptor blocker is the preferred antihypertensive choice. Finally, multidisciplinary collaboration in these patients will yield the best results.

Local anesthetics for the Nephrologist.

Several specialists in medicine use local anesthetics. In patients with kidney disease, these agents are used during catheter insertions for hemodialysis and peritoneal dialysis, arteriovenous fistula and graft procedures, kidney transplantation, parathyroidectomy, kidney biopsies, and dental and skin procedures. Patients on chronic hemodialysis use a topical application prior to use of needles for arteriovenous fistula cannulation before starting dialysis. They are also used to manage acute and chronic pain conditions, in regional nerve blockade and in multi-modal enhanced recovery protocols. Despite their frequent use by both physicians and patients, data on the use of local anesthetics in patients with kidney impairment are not well reported. This review will summarize the use of local anesthetics in chronic kidney disease, describe their pharmacology and the impact of lower estimated glomerular filtration rate on their pharmacokinetics, and suggest dose regulation in those with kidney dysfunction.

Erratum to: Local anesthetics for the Nephrologist.

[This corrects the article DOI: 10.1093/ckj/sfab121.].

Outcomes of patients with end-stage kidney disease hospitalized with COVID-19.

Given the high risk of infection-related mortality, patients with end-stage kidney disease (ESKD) may be at increased risk with COVID-19. To assess this, we compared outcomes of patients with and without ESKD, hospitalized with COVID-19. This was a retrospective study of patients admitted with COVID-19 from 13 New York hospitals from March 1, 2020, to April 27, 2020, and followed through May 27, 2020. We measured primary outcome (in-hospital death), and secondary outcomes (mechanical ventilation and length of stay). Of 10,482 patients with COVID-19, 419 had ESKD. Patients with ESKD were older, had a greater percentage self-identified as Black, and more comorbid conditions. Patients with ESKD had a higher rate of in-hospital death than those without (31.7% vs 25.4%, odds ratio 1.38, 95% confidence interval 1.12 - 1.70). This increase rate remained after adjusting for demographic and comorbid conditions (adjusted odds ratio 1.37, 1.09 - 1.73). The odds of length of stay of seven or more days was higher in the group with compared to the group without ESKD in both the crude and adjusted analysis (1.62, 1.27 - 2.06; vs 1.57, 1.22 - 2.02, respectively). There was no difference in the odds of mechanical ventilation between the groups. Independent risk factors for in-hospital death for patients with ESKD were increased age, being on a ventilator, lymphopenia, blood urea nitrogen and serum ferritin. Black race was associated with a lower risk of death. Thus, among patients hospitalized with COVID-19, those with ESKD had a higher rate of in-hospital death compared to those without ESKD.

Hypoglycemia in Patients with Type 2 Diabetes Mellitus and Chronic Kidney Disease: A Prospective Observational Study.

Background: Glycemic management in patients with type 2 diabetes mellitus (T2DM) and CKD can become complicated. One factor that may affect treatment is hypoglycemia. Hypoglycemia risk may be increased by several biologic processes in CKD. The objective of this study was to determine the frequency, severity, and risk factors for hypoglycemia in patients with T2DM and CKD. Methods: The design was a prospective observational study. A continuous glucose monitor (CGM) was worn by 80 patients for up to 14 days; glucose was measured every 15 minutes. Patients with T2DM and eGFR <45 ml/min were enrolled. Patients on dialysis were excluded. The primary outcome was to assess the frequency of hypoglycemic episodes during the study period. Hypoglycemic episodes were defined as a reduced glucose concentration (<70 mg/dl) lasting ≥15 minutes. Secondary outcomes included assessment of severity of hypoglycemia and risk factors for its development. Results: A total of 80 patients wore the CGM for a mean of 12.7±2.9 days. Hypoglycemic events occurred in 61 of 80 patients (76%) with glucose <70 mg/dl, and 49 of 80 (61%) with glucose <60 mg/dl. Prolonged hypoglycemic events (CGM glucose <54 mg/dl for ≥120 consecutive minutes) occurred in 31 patients (39%) with 118 total events. Most hypoglycemic episodes occurred overnight, from 1:00 am to 9:00 am. By multivariate analysis, lower hemoglobin A1c and treatment with insulin were two modifiable risk factors for hypoglycemic events. Conclusions: Patients with T2DM and CKD have frequent periods of hypoglycemia that can be severe and prolonged. Hemoglobin A1c does not portray the full scope of hypoglycemia risk. This study illustrates the need for careful monitoring of glucose levels in patients with T2DM and CKD.

The Demystification of Secondary Hypertension: Diagnostic Strategies and Treatment Algorithms.

PURPOSE OF REVIEW: Hypertension is one of the most common conditions encountered in the primary care setting, affecting 32-46% of people. While essential or primary hypertension is the most common form of the disease, secondary hypertension is quite prevalent, occurring in 10-20% of patients with hypertension. Accurately diagnosing secondary hypertension is a challenging and often time-consuming process that requires considerable expertise and effort. However, once the secondary etiology is identified, the patient benefits profoundly from a potentially curative treatment that may lead to significant improvements in quality of life, morbidity, and mortality. RECENT FINDINGS: Common causes of secondary hypertension include medication-induced hypertension, renal parenchymal disease, renovascular hypertension, obstructive sleep apnea, and primary aldosteronism. Other rarer forms include mineralocorticoid-driven hypertension or its mimics, as well as hypercortisolism and pheochromocytoma. Although complex, standard protocols have emerged for investigation, diagnosis, and treatment of these conditions. The current review aims to elucidate the many causes of secondary hypertension and describe their respective prevalence, clinical presentation, screening, diagnosis, treatment, and follow-up. By demystifying secondary hypertension, it is hoped that this disease will be more easily identified and treated so that the associated cardiovascular morbidity and end-organ damage may be mitigated.

Continuous Glucose Monitoring and Glycemic Control in Patients With Type 2 Diabetes Mellitus and CKD.

RATIONALE & OBJECTIVE: The accuracy of glycated hemoglobin (HbA1c) level for assessment of glycemic control in patients with chronic kidney disease (CKD) is uncertain. This study assessed the accuracy of HbA1c level using continuous glucose monitoring. STUDY DESIGN: Diagnostic test study of HbA1c and serum fructosamine. The continuous glucose monitor was worn for 14 days. Glucose was measured every 15 minutes (up to 1,344 measurements). Average glucose concentration was calculated for each patient from the patient's continuous glucose monitor measurements. Linear regression was applied to estimate the relationship between average glucose concentration and HbA1c and serum fructosamine levels. The influence of patient characteristics on the relationship between HbA1c and average glucose concentrations was examined in a multivariate regression model. SETTING & PARTICIPANTS: Patients with type 2 diabetes and CKD (estimated glomerular filtration rate, 7-45 mL/min, not receiving dialysis) seen in an academic nephrology clinic. TESTS ANALYZED: The accuracy of HbA1c level for assessment of chronic glycemia. A secondary objective was to study serum fructosamine levels. OUTCOMES: The degree of correlation between continuous glucose monitoring-derived average glucose concentration and HbA1c level; serum fructosamine level was studied as a secondary outcome. RESULTS: 80 patients wore the continuous glucose monitor for a mean of 12.7 ± 2.9 days. Average glucose concentration of all patients was 151.5 ± 55.7 mg/dL. Mean HbA1c level was 7.2% ± 1.5%. HbA1c level was highly correlated with average glucose concentration, described by the equation: average glucose concentration = 30.48 × HbA1c - 68.48; r = 0.82; P < 0.001. Serum fructosamine level was also significantly correlated with average glucose concentration; r = 0.55; P < 0.001. The strong correlation between average glucose concentration and HbA1c level was not affected by the severity of CKD, whereas the performance of serum fructosamine level, in contrast, degraded among patients with more severe CKD. LIMITATIONS: Relatively small sample size. CONCLUSIONS: HbA1c is an accurate measure of glycemic status among patients with CKD and type 2 diabetes. This relationship appears to hold true among patients with more severe CKD.

Factors associated with completion of pre-kidney transplant evaluations.

This study sought to examine various factors that may prevent transplant candidates from completing their transplant workup prior to listing. We reviewed the records of 170 subjects (cases = 100, controls 70) who were either on dialysis or had less than 20 mL/min creatinine clearance and were therefore candidates for preemptive transplantation. Approximately, 56% of preemptive patients completed their workup, while only 36% of patients on dialysis completed their workup. Our data revealed that factors contributing toward completion of workup included intrinsic motivation (four times more likely), lack of specific medical comorbidities (three times more likely), and preemptive status (two times more likely). Among patients on dialysis, intrinsic motivation (five times more likely) and absence of cardiovascular complications (four times more likely) were associated with completion. When comparing patients on dialysis to patients not on dialysis, there were significant differences between the two groups in distance from home to the transplant center, level of education, and presence of medical comorbidities. We believe that targeted interventions such as timely referral, providing appropriate educational resources, and development of adequate support systems, have the potential to improve workup compliance of patients with advanced chronic kidney disease, including those on dialysis.

Treatment with erythropoiesis-stimulating agents in chronic kidney disease patients with cancer.

Treatment of anemia remains an important component in the care of patients with nondialysis chronic kidney disease (CKD) and end-stage renal disease (ESRD). Erythropoietin-stimulating agents (ESAs) remains a key anemia treatment strategy in this patient population. However, anemia management in this group can become more complicated by prior or current history of malignancy. There has been a great deal of work both scientifically and in clinical trials in oncology that have revealed certain concerns and risks of ESA use in patients with cancer. In this review, we will bring together knowledge from nephrology and oncology literature to help nephrologists understand the implications for ESA treatment when CKD/ESRD is complicated by cancer. We also suggest an approach to the management of anemia in this patient group with active or previous malignancy.

Relationship between dialysate oxidized protein and peritoneal membrane transport properties in patients on peritoneal dialysis.

BACKGROUND: Increased levels of oxidized proteins have been reported in the serum of patients with end-stage renal disease, though little is known regarding the oxidized protein content of the dialysate in patients on peritoneal dialysis (PD) and no information is available as to how this may correlate with important clinical and laboratory variables, including abnormal peritoneal membrane function. In this study we attempted to identify oxidized proteins in the dialysate of patients on PD using western blot analysis, and examined the relationship between these proteins and the function of the peritoneal membrane and other clinical and laboratory variables. METHODS: Peritoneal dialysate and serum samples were obtained from 18 patients on PD, and western blot analysis using an antibody to oxidized protein was carried out with reprobing for albumin. Oxidized protein/albumin ratios were determined and compared with various clinical and laboratory variables including peritoneal equilibration test results. RESULTS: Oxidized protein/albumin ratios were higher in the dialysate of patients who were high/high average transporters compared to low/low average transporters. Oxidized protein ratios were also found to be higher in the dialysate of patients who had diminished urine output as a reflection of loss of residual renal function. Negative correlations were noted between oxidized protein ratios in the dialysate and serum albumin levels and creatinine clearance. CONCLUSIONS: Higher levels of oxidized protein in the dialysate appear to be correlated with high/high average peritoneal membrane transport characteristics and may be related to loss of residual renal function. These preliminary findings suggest that it is plausible that oxidized proteins in the dialysate might play a contributory role in complications including membrane damage and ultrafiltration failure in patients on PD.

Vancomycin-induced acute granulomatous interstitial nephritis: therapeutic options.

Drug-induced acute renal failure is a commonly encountered mode of renal injury in the hospitalized patient. Vancomycin is a frequently used antibiotic in patients with Gram-positive bacterial infections. In the present study, we evaluated an index case of a patient who developed severe acute granulomatous interstitial nephritis and provided a review of the reported cases of vancomycin-induced acute renal failure in the literature. A Medline search revealed a total of 11 cases of vancomycin-induced interstitial nephritis. In 2 reported cases, interstitial nephritis has been reported with associated granuloma formation. However, the role of T cells in the formation of interstitial nephritis and in the choice of therapeutic modalities in this scenario has not been evaluated in the past. In the index case, we have evaluated the effect of treatment on the basis of the type of cellular infiltrates and provided a follow-up by carrying out the repeat biopsy.