The impact of COVID-19 on kidney transplantation and the kidney transplant recipient - One year into the pandemic.

The COVID-19 pandemic has significantly changed the landscape of kidney transplantation in the United States and worldwide. In addition to adversely impacting allograft and patient survival in postkidney transplant recipients, the current pandemic has affected all aspects of transplant care, including transplant referrals and listing, organ donation rates, organ procurement and shipping, and waitlist mortality. Critical decisions were made during this period by transplant centers and individual transplant physicians taking into consideration patient safety and resource utilization. As countries have begun administering the COVID vaccines, new and important considerations pertinent to our transplant population have arisen. This comprehensive review focuses on the impact of COVID-19 on kidney transplantation rates, mortality, policy decisions, and the clinical management of transplanted patients infected with COVID-19.

The landscape of renal replacement therapy in Veterans Affairs Medical Center intensive care units.

BACKGROUND: Outpatient dialysis is standardized with several evidence-based measures of adequacy and quality that providers aim to meet while providing treatment. By contrast, in the intensive care unit (ICU) there are different types of prolonged and continuous renal replacement therapies (PIRRT and CRRT, respectively) with varied strategies for addressing patient care and a dearth of nationally accepted quality parameters. To eventually describe appropriate quality measures for ICU-related renal replacement therapy (RRT), we first aimed to capture the variety and prevalence of basic strategies and equipment utilized in the ICUs of Veteran Affairs (VA) medical facilities with inpatient hemodialysis capabilities. METHODS: Via email to the dialysis directors of all VA facilities that provided inpatient hemodialysis during 2018, we requested survey participation regarding aspects of RRT in VA ICUs. Questions centered around the mode of therapy, equipment, solutions, prescription authority, nursing, anticoagulation, antimicrobial dosing, and access. RESULTS: Seventy-six centers completed the questionnaire, achieving a response rate of 87.4%. Fifty-five centers reported using PIRRT or CRRT in addition to intermittent hemodialysis. Of these centers, 42 reported being specifically CRRT-capable. Over half of respondents had the capabilities to perform PIRRT. Twelve centers (21.8%) were equipped to use slow low efficient dialysis (SLED) alone. Therapy was largely prescribed by nephrologists (94.4% of centers). CONCLUSIONS: Within the VA system, ICU-related RRT practice is quite varied. Variation in processes of care, prescription authority, nursing care coordination, medication management, and safety practices present opportunities for developing cross-cutting measures of quality of intensive care RRT that are agnostic of modality choice.

Trends in the Causes of Death among Kidney Transplant Recipients in the United States (1996-2014).

BACKGROUND: Death with graft function remains an important cause of graft loss among kidney transplant recipients (KTRs). Little is known about the trend of specific causes of death in KTRs in recent years. METHODS: We analyzed United States Renal Data System data (1996-2014) to determine 1- and 10-year all-cause and cause-specific mortality in adult KTRs who died with a functioning allograft. We also studied 1- and 10-year trends in the various causes of mortality. RESULTS: Of 210,327 KTRs who received their first kidney transplant from 1996 to 2014, 3.2% died within 1 year after transplant. Cardiovascular deaths constituted the majority (24.7%), followed by infectious (15.2%) and malignant (2.9%) causes; 40.1% of deaths had no reported cause. Using 1996 as the referent year, all-cause as well as cardiovascular mortality declined, whereas mortality due to malignancy did not. For analyses of 10-year mortality, we studied 94,384 patients who received a first kidney transplant from 1996 to 2005. Of those, 22.1% died over 10 years and the causative patterns of their causes of death were similar to those associated with 1-year mortality. CONCLUSIONS: Despite the downtrend in mortality over the last 2 decades, a significant percentage of KTRs die in 10-years with a functioning graft, and cardiovascular mortality remains the leading cause of death. These data also highlight the need for diligent collection of mortality data in KTRs.

Proton Pump Inhibitor Use and Risk of Hip Fracture in Kidney Transplant Recipients.

BACKGROUND: Posttransplantation bone disease is a significant problem, with few well-evidenced therapeutic options. Proton pump inhibitors (PPIs) are associated with hip fracture in the general population and are widely prescribed for kidney transplant recipients. STUDY DESIGN: A case-control study. SETTING & PARTICIPANTS: From the US Renal Data System, we identified from diagnoses and procedures 231 kidney transplant recipients with a first hip fracture. Cases were matched at the hip fracture index date with 15,575 controls on age, sex, race, and transplantation year. PREDICTOR: PPI use. OUTCOMES: First hip fracture. RESULTS: In the year prior to the index date, a PPI was prescribed to 65.4% of cases and 57.4% of controls. Additionally, in 34.6% of cases and 28.9% of controls, a PPI was prescribed for >80% of the year preceding the index date (higher PPI users). Unadjusted ORs of hip fracture associated with any and higher PPI use were 1.55 (95% CI, 1.18-2.05) and 1.65 (95% CI, 1.2-2.27), respectively. When adjusted for baseline demographic, clinical, and pharmacologic covariables, any and higher PPI use remained associated with hip fracture, with ORs of 1.39 (95% CI, 1.04-1.84) and 1.41 (95% CI, 1.02-1.95), respectively. LIMITATIONS: Potential residual confounding through either incorrectly ascertained or unavailable confounders; cohort limited to Medicare beneficiaries receiving low-income subsidy. CONCLUSIONS: In summary, PPI use was associated with hip fracture risk in the US kidney transplant population.

Ileostomy creation in colorectal cancer surgery: risk of acute kidney injury and chronic kidney disease.

BACKGROUND: Ileostomy creation is associated with postoperative dehydration and readmission; however, the effect on renal function is unknown. Our goal was to characterize the impact of ileostomy creation on acute and chronic renal function. MATERIALS AND METHODS: A retrospective cohort study with patients undergoing colorectal cancer surgery at a tertiary referral institution (2005-2011). The relationship between ileostomy creation and acute kidney injury (AKI)-related readmission, severe chronic kidney disease (CKD) at 12 mo (glomerular filtration rate <30 mL/min/1.73 m2), and onset of severe CKD over time was evaluated using multivariable logistic and Cox regression and adjusted using propensity score stratification. RESULTS: Among 619 patients, 84 (13%) had ileostomy. AKI-related readmission and severe CKD at 12 mo were more common among ileostomy patients (17% versus 2%, P < 0.01 and 13.3% versus 5%, P = 0.02, respectively). After propensity score adjustment, ileostomy was a significant predictor of AKI-related readmissions (odds ratio: 10.3; 95% confidence interval [CI], 3.9-27.2), severe CKD at 12 mo (odds ratio: 4.1; 95% CI, 1.4-11.9), and onset of severe CKD over time (hazard ratio: 4.2; 95% CI, 2.3-6.6). CONCLUSIONS: Ileostomy creation is associated with increased risk of AKI-related readmissions and development of severe CKD. Future studies must focus on strategies to minimize kidney injury when ileostomy is a necessary component of colorectal cancer surgery and revisiting current indications for ileostomy creation.

Statin use and hip fractures in U.S. kidney transplant recipients.

BACKGROUND: Basic and translational research supports beneficial effects of statins on bone metabolism. Clinical studies suggest that statin use may reduce the risk of hip fractures in the general population. Whether statin use is associated with hip fracture risk in kidney transplant recipients, a particularly high-risk group for this outcome, is unknown. METHODS: From the U.S. Renal Data System (2007-2011), we identified all hip fracture events recorded in Medicare billing claims of first-time kidney transplant recipients. We then matched all cases to an unlimited number of controls on age (±3 years), sex, race (black vs. non-black), and time since transplant. Cases and controls were required to have >1 year of Medicare Parts A + B + D coverage and be without a recorded history of hip fracture. We ascertained any statin use in the previous year and defined adherent statin use as those who had filled prescriptions for statins to cover >80% of days in that year (proportion of days covered, PDC). We ascertained several potential confounders (demographics, comorbidities, BMI, transplant-related factors) and applied conditional logistic regression with multiple imputation for missing data to estimate odds ratios (OR) and 95% confidence intervals (CI). RESULTS: We identified 231 hip fracture cases (mean age 51.8 years; 53% female; 11.3% black; 6.9 years from transplant, and 9.9 years from ESRD) and 15,575 matched controls. Any prior statin use was present in 64.1% of cases and 60.3% of controls with 37.2% of cases and 33.9% of controls being found adherent. Unadjusted conditional logistic regression showed an OR of 1.17 (0.89-1.54) for any statin use, and a fully-adjusted OR of 0.89 (0.67-1.19). Compared with statin non-users, the adjusted OR for patients with lesser adherence (PDC ≤80%) and those with greater adherence (PDC >80%) were 0.93 (0.66-1.31) and 0.87 (0.63-1.20), respectively. CONCLUSION: Statin use was not associated with hip fracture risk in first-time kidney transplant recipients.

Severe encephalopathy following cerebral arteriogram in a patient with end-stage renal disease.

Disruption of blood brain barrier (BBB) with subsequent subarachnoid contrast extravasation and cerebral edema is a rare complication of intra-arterial contrast administration. We report a patient with end-stage renal disease (ESRD) who developed such a complication. A 63-year-old man with a history of left orbital apex syndrome on hemodialysis (HD) was admitted with massive epistaxis. A pseudo-aneurysm of the left internal carotid artery (ICA) required a cerebral arteriogram with coil embolization; a total of 910 ml of isosmolar intra-arterial contrast was used. Shortly thereafter, the patient developed severe alteration in his mental status. A CT study without contrast of the head showed bilateral subarachnoid hyper-attenuation with diffuse cerebral edema consistent with contrast-induced encephalopathy syndrome. The patient was urgently and repetitively dialyzed to remove the contrast leading to a remarkable improvement in his mental status and resolution of both subarachnoid hyper-attenuation and brain edema. The large volume of intra-arterial contrast that may be required in neurologic interventional procedures is occasionally associated with breakdown of BBB leading to subarachnoid accumulation and cerebral edema resulting in a severe encephalopathy syndrome. Hemodialysis seems particularly well suited for the patient who has renal failure in whom this syndrome develops.

Systematic review: hepatitis C viraemic allografts to hepatitis C-negative recipients in solid organ transplantation.

BACKGROUND: Given the success of direct-acting antivirals (DAAs) in treating hepatitis C (HCV), interest is growing in utilizing solid organs from allografts with active HCV to expand donor availability. AIM: To review post-transplant outcomes and patient survival in HCV-negative recipients receiving solid organ transplants (SOT) from viraemic, that is, HCV+/NAT+ (nucleic acid testing) allografts. METHODS: A literature search was conducted on PubMed and EMBASE from 01/01/2007 to 4/17/2021 for articles matching eligibility criteria. Two authors independently screened titles and abstracts. Disagreements were solved by a third independent reviewer. Methodological quality assessment was done using a modified Newcastle-Ottawa scale (NOS). Data synthesis was done qualitatively using median, ranges and percentages. RESULTS: Thirty-five studies were included (or 852 SOTs): 343 kidney, 233 heart, 204 liver, and 72 lung transplants from viraemic allografts. Of the recipients eligible for sustained virological response at 12 weeks (SVR12) calculation, 100% achieved cure from HCV. No deaths/graft failures were reported to be related to HCV transmission. Seven SOT recipients had viral relapse, with all seven patients treated successfully. Four patients developed fibrosing cholestatic hepatitis with complete resolution post-treatment. CONCLUSIONS: Transplanting viraemic organs into uninfected individuals can become the standard of care for patients who do not have contraindications to DAAs.

Mineral and Bone Disorders After Kidney Transplantation.

The risk of mineral and bone disorders among patients with chronic kidney disease is substantially elevated, owing largely to alterations in calcium, phosphorus, vitamin D, parathyroid hormone, and fibroblast growth factor 23. The interwoven relationship among these minerals and hormones results in maladaptive responses that are differentially affected by the process of kidney transplantation. Interpretation of conventional labs, imaging, and other fracture risk assessment tools are not standardized in the post-transplant setting. Post-transplant bone disease is not uniformly improved and considerable variation exists in monitoring and treatment practices. A spectrum of abnormalities such as hypophosphatemia, hypercalcemia, hyperparathyroidism, osteomalacia, osteopenia, and osteoporosis are commonly encountered in the post-transplant period. Thus, reducing fracture risk and other bone-related complications requires recognition of these abnormalities along with the risk incurred by concomitant immunosuppression use. As kidney transplant recipients continue to age, the drivers of bone disease vary throughout the post-transplant period among persistent hyperparathyroidism, de novo hyperparathyroidism, and osteoporosis. The use of anti-resorptive therapies require understanding of different options and the clinical scenarios that warrant their use. With limited studies underscoring clinical events such as fractures, expert understanding of MBD physiology, and surrogate marker interpretation is needed to determine ideal and individualized therapy.

Facility-Level Variations in Kidney Disease Care among Veterans with Diabetes and CKD.

BACKGROUND AND OBJECTIVES: Facility-level variation has been reported among veterans receiving care for various diseases. We studied the frequency and facility-level variations of guideline-recommended practices in patients with diabetes and CKD. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: Patients with diabetes and concomitant CKD (eGFR 15-59 ml/min per 1.73 m2, measured twice, 90 days apart) receiving care in 130 facilities across the Veterans Affairs Health Care System were included (n=281,223). We studied the proportions of patients (facility-level) receiving recommended core measures and facility-level variations of these study outcomes using median rate ratios, adjusting for various patient and provider-level factors. Median rate ratio quantifies the degree to which care may vary for similar patients receiving care at two randomly chosen facilities, with <1 being no variation and >1.2 as substantial variation between the facilities. Study outcomes included measurement of urine albumin-to-creatinine ratio/urine protein-to-creatinine ratio and blood hemoglobin concentration, prescription of statins and angiotensin-converting enzyme inhibitors/angiotensin receptor blockers, BP<140/90 mm Hg, and referral to a Veterans Affairs nephrologist (only for those with eGFR<30 ml/min per 1.73 m2). RESULTS: Among those with eGFR 30-59 ml/min per 1.73 m2, proportion of patients receiving recommended core measures (median and interquartile range across facilities) were 37% (22%-47%) for urine albumin-to-creatinine ratio/urine protein-to-creatinine ratio, 74% (72%-79%) for hemoglobin measurement, 66% (62%-69%) for angiotensin-converting enzyme inhibitor/angiotensin receptor blocker prescription, 85% (74%-87%) for statin prescription, 47% (42%-53%) for achieving BP<140/90 mm Hg, and 13% (7%-16%) for meeting all outcome measures. Adjusted median rate ratios (95% confidence intervals) were 5.2 (4.1 to 6.4), 2.4 (2.1 to 2.6), 1.3 (1.2 to 1.3), 1.2 (1.2 to 1.3), 1.4 (1.3 to 1.4), and 4.1 (3.3 to 5.0), respectively. Median rate ratios were qualitatively similar in an analysis restricted to those with eGFR 15-29 ml/min per 1.73 m2. CONCLUSIONS: Among patients with diabetes and CKD, at facility-level, ordering of laboratory tests, and scheduling of nephrology referrals in eligible patients remains suboptimal, with substantial variations across facilities.

Prevention and management of hemodialysis catheter infections.

Hemodialysis (HD) catheters are associated with blood stream infections, and catheter use continues to be high among incident and prevalent patients on maintenance HD. Migration of micro-organism along the external surface of the catheter is probably the most common route of infection, followed by the endoluminal route of contamination. Almost all HD catheters have biofilm formation on their surfaces and this serves as a good reservoir for micro-organisms. These active but protected microorganisms have been implicated in local and systemic infections associated with HD catheters. Good personal hygiene, exit-site care with topical antibiotics and antibiotic lock solution in the dialysis catheter reduce the incidence of catheter infection. In selected subgroup of patients, HD catheter is promptly removed after the diagnosis of blood stream infection. However, catheter guidewire exchange is an acceptable alternate strategy in some patients. The most important goal should be to increase the rate of incident arteriovenous fistula use in the HD population.

Pilot trial of N-acetylcysteine and tigecycline as a catheter-lock solution for treatment of hemodialysis catheter-associated bacteremia.

We evaluated a catheter-lock solution consisting of N-acetylcysteine, tigecycline, and heparin for catheter salvage in patients with hemodialysis catheter-associated bacteremia. Eighteen case patients received the catheter-lock solution for 14 days plus systemic antibiotic therapy. Treatment was successful for 15 (83%) of the 18 case patients within 90 days of follow-up, with a median catheter retention interval of 64.5 days.

Combination of tigecycline and N-acetylcysteine reduces biofilm-embedded bacteria on vascular catheters.

To assess the efficacy of an antibiofilm/antimicrobial agent combination, we incubated catheter segments colonized with one of six studied bacterial organisms in N-acetylcysteine, tigecycline, N-acetylcysteine-tigecycline, or saline. Segments were washed, sonicated, and cultured. N-acetylcysteine-tigecycline significantly decreased all viable biofilm-associated bacteria and was synergistic for methicillin-resistant Staphylococcus aureus and Staphylococcus epidermidis.

Granulomatous pyelitis associated with urinary obstruction: a comprehensive clinicopathologic study.

Urinary obstruction is rarely associated with a distinct granulomatous inflammation, which involves the pyelocalyceal system and closely simulates infectious conditions including tuberculosis. Its clinicopathologic features, however, have not been adequately studied since there are only seven isolated reported cases. In a comprehensive study of 112 kidney specimens with urinary obstruction, we identified five cases of granulomatous pyelitis. The features of these cases were detailed and compared with the previously reported cases. Among the five identified subjects, three patients had history of urolithiasis and two had ureteral stenosis and all had stent placement 7 weeks to 12 years before nephrectomy for relief of the unilateral urinary obstruction. The age distribution was between 38 and 81 years. Two had end-stage renal disease or chronic renal failure. The pyelocaliceal system showed frank hydronephrosis (1 case) or partial dilatation (4 cases) and contained cheesy and gritty material in its lumen. Each case showed severe granulomatous inflammation, which was limited to the pelvic wall and closely associated with calcified debris, necrotic inflammatory cells, and material consistent with Tamm-Horsfall protein. The kidney showed chronic tubulointerstitial nephritis but without granulomas. Cultures of urine, blood, and the renal pelvic content, and special stains of tissue sections did not show fungi or mycobacteria in any case. Many of these features were also observed in previously reported cases. Granulomatous pyelitis is a rare but distinct cliniocopathologic entity characterized by severe noninfectious granulomatous inflammation limited to the renal pelvis, which is uniformely asociated with urinary obstruction and pyelocalyceal dilatation and may develop in response to accumulated calcified material in the renal pelvis. Awareness of this entity and its characteristic clinicopathologic features also helps eliminate an infectious etiology with obvious treatment and prognostic implications.