Is Exclusion of Coronary Artery Disease in the Kidney Allocation System Preventing Optimal Longevity Matching?

BACKGROUND: Coronary artery disease (CAD) in a kidney transplant candidate is an important predictor of posttransplant mortality. It is not known how the exclusion of CAD in the kidney allocation system has impacted its goal of longevity matching. METHODS: This is an observational study on adult deceased donor kidney transplant alone recipients between December 4, 2014, and December 31, 2018, with Medicare fee for service (FFS) insurance. Patients were categorized on the basis of Kidney Donor Profile Index (KDPI), Estimated Posttransplant Survival (EPTS), and CAD. Outcomes studied were mortality, death with a functioning graft, overall graft loss, and death-censored graft loss. RESULTS: Among 21 151 patients with Medicare FFS coverage for >1 y before transplant, there were 2869 and 18 282 patients with and without CAD, respectively. On Kaplan-Meier analysis, there was higher risk of mortality, death with a functioning graft, overall graft loss, and death-censored graft loss with CAD ( P < 0.05 for all). Mortality was higher for CAD group within each category of KDPI and among patients with Estimated Posttransplant Survival 0% to 20% receiving kidneys with KDPI <20% ( P < 0.001 for all). On Cox multivariate analysis, the hazard ratios (HRs) of mortality and graft loss were higher with CAD diagnosis without intervention (HR 1.38 [1.25-1.52] and 1.29 [1.18-1.4]), CAD with stents (HR 2.76 [1.68-4.53] and 2.36 [1.46-3.81]), and CAD with bypass surgery (HR 1.56 [1.29-1.89] and 1.39 [1.17-1.65]). Posttransplant CAD events were higher in patients with preexisting CAD ( P < 0.001). CONCLUSIONS: The exclusion of a candidate's history of CAD in the kidney allocation system adversely impacts its goal of optimal longevity matching.

Dual impact of donor service area removal from kidney allocation system and Coronavirus Disease 2019 pandemic on access to transplantation.

INTRODUCTION: Donor service area was removed from kidney and pancreas allocation system in the United States on March 15, 2021 in favor of a distance based policy to provide geographic equity to access to transplantation. The policy change was introduced at a time when ongoing Coronavirus Disease 2019 (COVID-19) pandemic cases were declining following the first delta wave. METHODS: In this Scientific Registry of Transplant Recipients based study, deceased donor kidney transplant recipients between March 15 and December 2 of 2019, 2020 and 2021 were compared representing pre-policy change, pre-COVID cohort; pre-policy change, early COVID cohort; and post-policy change, late COVID cohort. RESULTS: There were 11336, 11808, and 12914 kidney transplants in the 2019, 2020, and 2021 cohorts, respectively. Proportion of kidney transplants increased from 8798 (78%) to 9496 (80%) to 11152 (86%), and decreased from 2538 (22%) to 2312 (20%) to 1762 (14%) within and beyond 250 nautical miles in subsequent years. Median distance between donor and transplant hospital increased (73 vs. 63 vs. 119 nautical miles, P < .001) and mean cold ischemia time increased (18.1 vs. 17.8 vs. 19.9 h, P < .001). Access to transplantation did not change for various racial groups (P = .07), pediatric patients (P = .29), dialysis vintage of >5 years (P = .21), veterans (P = .07) and decreased for those with calculated PRA of 99% and 100% (P < .001). Rate of kidney discard (19.6% vs. 20.4% vs. 24%) remained high. Although there were numerical increases in transplants from donors with donation after circulatory death, donor acute kidney injury, kidney donor profile index >85% and donor age >60 years in successive years, rates of kidney discard also increased proportionally. CONCLUSION: Improvement in the access to transplantation following the policy change was attenuated by the concurrent prevalence of the COVID-19 pandemic.

Impact of Size Matching Based on Donor-Recipient Height on Kidney Transplant Outcomes.

Transplantation of kidneys from shorter donors into taller recipients may lead to suboptimal allograft survival. The effect of discrepancy in donor and recipient heights (ΔHeight) on long term transplant outcomes is not known. Adult patients ≥18 years undergoing living or deceased donor (LD or DD) kidney transplants alone from donors ≥18 years between 2000 and 2016 in the United States were included in this observational study. The cohort was divided into three groups based on ΔHeight of 5 inches as 1) Recipient < Donor (DD: 31,688, LD: 12,384), 2) Recipient = Donor (DD: 84,711, LD: 54,709), and 3) Recipient > Donor (DD: 21,741, LD: 18,753). Univariate analysis showed a higher risk of DCGL and mortality in both DD and LD (p < 0.001 for both). The absolute difference in graft and patient survival between the two extremes of ΔHeight was 5.7% and 5.7% for DD, and 0.4% and 1.4% for LD. On multivariate analysis, the HR of DCGL for Recipient < Donor and Recipient > Donor was 0.95 (p = 0.05) and 1.07 (p = 0.01) in DD and 0.98 (p = 0.55) and 1.14 (p < 0.001) in LD. Similarly, the corresponding HR of mortality were 0.97 (p = 0.07) and 1.07 (p = 0.003) for DD and 1.01 (p < 0.001) and 1.05 (p = 0.13) for LD. For DGF, the HR were 1.04 (p = 0.1) and 1.01 (p = 0.7) for DD and 1.07 (p = 0.45) and 0.89 (p = 0.13) for LD. Height mismatch between the donor and recipient influences kidney transplant outcomes.

Impact of Subclinical and Clinical Kidney Allograft Rejection Within 1 Year Posttransplantation Among Compatible Transplant With Steroid Withdrawal Protocol.

Early acute kidney rejection remains an important clinical issue. METHODS: The current study included 552 recipients who had 1-2 surveillance or indication biopsy within the 1 y posttransplant. We evaluated the impact of type of allograft inflammation on allograft outcome. They were divided into 5 groups: no inflammation (NI: 95), subclinical inflammation (SCI: 244), subclinical T cell-mediated rejection (TCMR) (SC-TCMR: 110), clinical TCMR (C-TCMR: 83), and antibody-mediated rejection (AMR: 20). Estimated glomerular filtration rate (eGFR) over time using linear mixed model, cumulative chronic allograft scores/interstitial fibrosis and tubular atrophy (IFTA) ≥2 at 12 mo, and survival estimates were compared between groups. RESULTS: The common types of rejections were C-TCMR (15%), SC-TCMR (19.9%), and AMR (3.6%) of patients. Eighteen of 20 patients with AMR had mixed rejection with TCMR. Key findings were as follows: (i) posttransplant renal function: eGFR was lower for patients with C-TCMR and AMR (P < 0.0001) compared with NI, SCI, and SC-TCMR groups. There was an increase in delta-creatinine from 3 to 12 mo and cumulative allograft chronicity scores at 12 mo (P < 0.001) according to the type of allograft inflammation. (ii) Allograft histology: the odds of IFTA ≥2 was higher for SC-TCMR (3.7 [1.3-10.4]; P = 0.04) but was not significant for C-TCMR (3.1 [1.0-9.4]; P = 0.26), and AMR (2.5 [0.5-12.8]; P = 0.84) compared with NI group, and (iii) graft loss: C-TCMR accounted for the largest number of graft losses and impending graft losses on long-term follow-up. Graft loss among patient with AMR was numerically higher but was not statistically significant. CONCLUSIONS: The type of kidney allograft inflammation predicted posttransplant eGFR, cumulative chronic allograft score/IFTA ≥2 at 12 mo, and graft loss.

Role of Serum (1,3)-Β-D-Glucan to Screen for Pneumocystis Pneumonia in Kidney Transplant Recipients.

BACKGROUND: Pneumocystis pneumonia is a common opportunistic infection in kidney transplant recipients caused by the ascomycetous fungi Pneumocystis jirovecii. Its clinical presentation of a progressive nonproductive cough, shortness of breath, and fever is nonspecific and often delays diagnosis and appropriate treatment. Moreover, the plain radiograph may show a spectrum of findings from normal to bilateral diffuse infiltrates. Detection of serum (1,3)-ß-D-glucan along with consistent clinical findings can be used as early screening tools to diagnose and initiate treatment for Pneumocystis pneumonia pending confirmation by bronchoscopy. METHODS: This case series describes 6 kidney transplant recipients who were diagnosed as having Pneumocystis pneumonia. The baseline demographic variables, presenting symptoms, radiographic findings, laboratory findings including lactate dehydrogenase and serum (1,3)-ß-D-glucan levels, bronchoscopy findings, and its timing in relation to a positive serum (1,3)-ß-D-glucan test, and response to treatment were collected. RESULTS: All 6 patients who completed the first 3 months of prophylaxis against Pneumocystis pneumonia with sulfamethoxazole-trimethoprim were diagnosed as having Pneumocystis pneumonia between 2 to 24 years post transplant. They initiated treatment early based on a positive serum (1,3)-ß-D-glucan and negative Histoplasma antigen and serum galactomannan test with a presumptive diagnosis of Pneumocystis pneumonia, which was later confirmed with a positive polymerase chain reaction on bronchoalveolar lavage fluid. CONCLUSIONS: Pneumocystis pneumonia is a common opportunistic fungal infection in immunosuppressed kidney transplant recipients, and use of serum (1,3)-ß-D-glucan can be used as an initial screening test for its early diagnosis and treatment.

Osmotic Demyelination Syndrome following Correction of Hyponatremia by ≤10 mEq/L per Day.

Background: Overly rapid correction of chronic hyponatremia may lead to osmotic demyelination syndrome. European guidelines recommend a correction to ≤10 mEq/L in 24 hours to prevent this complication. However, osmotic demyelination syndrome may occur despite adherence to these guidelines. Methods: We searched the literature for reports of osmotic demyelination syndrome with rates of correction of hyponatremia ≤10 mEq/L in 24 hours. The reports were reviewed to identify specific risk factors for this complication. Results: We identified 19 publications with a total of 21 patients that were included in our analysis. The mean age was 52 years, of which 67% were male. All of the patients had community-acquired chronic hyponatremia. Twelve patients had an initial serum sodium <115 mEq/L, of which seven had an initial serum sodium ≤105 mEq/L. Other risk factors identified included alcohol use disorder (n=11), hypokalemia (n=5), liver disease (n=6), and malnutrition (n=11). The maximum rate of correction in patients with serum sodium <115 mEq/L was at least 8 mEq/L in all but one patient. In contrast, correction was <8 mEq/L in all but two patients with serum sodium ≥115 mEq/L. Among the latter group, osmotic demyelination syndrome developed before hospital admission or was unrelated to hyponatremia overcorrection. Four patients died (19%), five had full recovery (24%), and nine (42%) had varying degrees of residual neurologic deficits. Conclusion: Osmotic demyelination syndrome can occur in patients with chronic hyponatremia with a serum sodium <115 mEq/L, despite rates of serum sodium correction ≤10 mEq/L in 24 hours. In patients with severe hyponatremia and high-risk features, especially those with serum sodium <115 mEq/L, we recommend limiting serum sodium correction to <8 mEq/L. Thiamine supplementation is advisable for any patient with hyponatremia whose dietary intake has been poor.

Primary Hyperaldosteronism in End-Stage Renal Disease: Diagnostic Challenges and Treatment Considerations.

An adrenal incidentaloma is defined as an adrenal mass measuring at least 1 cm that is discovered surreptitiously in an imaging study done for reasons other than the evaluation of adrenal disease. The increase in the prevalence of adrenal incidentalomas has paralleled the increase in diagnostic imaging done for evaluation of other abdominal pathologies. However, most of these adrenal incidentalomas are benign non-hyperfunctioning adenomas. When an adrenal incidentaloma is discovered, the simultaneous presence of hypokalemia, metabolic alkalosis, mild hypernatremia, and mild to severe drug-resistant hypertension may alert a clinician to underlying primary hyperaldosteronism. We present a case of adrenal incidentaloma noted in a patient with end-stage renal disease on hemodialysis which presented a diagnostic challenge due to the correction of metabolic parameters with hemodialysis. The patient was found to have an aldosterone-producing adenoma based on an elevated aldosterone-to-renin ratio and was started on a mineralocorticoid antagonist.

Severe Hyponatremia and Continuous Renal Replacement Therapy: Safety and Effectiveness of Low-Sodium Dialysate.

RATIONALE & OBJECTIVE: In patients with severe hyponatremia in the setting of acute kidney injury or end-stage kidney disease, continuous renal replacement therapy (CRRT) using standard-sodium (140 mEq/L) fluids may lead to excessively rapid correction of plasma sodium concentration. Use of dialysate and replacement fluids with reduced sodium concentrations can provide a controlled rate of correction of plasma sodium concentration. STUDY DESIGN: We performed a single-center retrospective analysis of the safety and effectiveness of this approach in patients with plasma sodium concentrations ≤ 126 mEq/L who underwent CRRT for 24 or more hours using low-sodium (119 or 126 mEq/L) dialysate and replacement fluids. Change in plasma sodium level was assessed at 24 and 48 hours after initiation of low-sodium CRRT and at the end of treatment. SETTING & PARTICIPANTS: Between January 2016 and June 2018, a total of 23 hyponatremic patients underwent continuous venovenous hemodiafiltration using low-sodium dialysate and replacement fluids; 4 patients were excluded from analysis because of CRRT duration less than <24 hours. RESULTS: The 19 patients included in the study had a mean age of 56 years, 11 (58%) were men, and 15 (79%) were white. The initial mean plasma sodium level was 121 mEq/L and the initial CRRT effluent dose was 27 mL/kg/h. Only 2 (11%) patients had an increase in plasma sodium concentration > 6 mEq/L at 24 hours. Mean changes in plasma sodium levels at 24 and 48 hours and at the time of CRRT discontinuation were 3, 3, and 6 mEq/L, respectively. None of the patients developed osmotic demyelination syndrome. LIMITATIONS: Key limitations were small sample size and lack of a control group. CONCLUSIONS: Use of low-sodium dialysate and replacement fluids is a safe strategy for the prevention of overly rapid correction of plasma sodium levels in hyponatremic patients undergoing CRRT.

Early subclinical tubulitis and interstitial inflammation in kidney transplantation have adverse clinical implications.

This prospective observational cohort study compared the impact of subclinical tubulitis with or without interstitial inflammation to interstitial inflammation alone and to no inflammation in early post kidney transplant biopsies. A study cohort of 415 patients (living and deceased donor recipients) was divided into three groups on the basis of their three-month biopsy: 149 patients with No Inflammation (NI), 83 patients with Isolated Interstitial Inflammation (IIF), and 183 patients with Tubulitis [(with or without interstitial inflammation) (TIF) but not meeting criteria for Banff IA]. TIF was further divided into 56 patients with tubulitis without interstitial inflammation (TIF0) and 127 patients with tubulitis alongside interstitial inflammation (TIF1). TIF was significantly associated with higher incidence of subsequent T-cell mediated rejection (clinical or subclinical) at one year compared to IIF (31% vs 15%) and NI (31% vs 17%). Chronicity on one-year biopsy was significantly higher in TIF compared to IIF (22% vs 11%) and NI (22% vs 7%). De novo donor-specific antibody development was significantly higher in TIF compared to NI (6% vs 0.7%). Tubulitis subgroups (TIF0 and TIF1) revealed comparable effects on de novo donor-specific antibody and interstitial fibrosis/tubular atrophy development. However, tubulitis with interstitial inflammation had a significantly higher incidence of subsequent rejection and posed an increased hazard for the composite end point (subsequent acute rejection and death censored graft loss) compared to other groups [adjusted hazard 2.1 (95% confidence interval 1.2-3.5)]. Thus, subclinical tubulitis is a marker of adverse immunological events, but tubulitis with interstitial inflammation has a worse prognosis. Hence, the Banff 1997 (TIF1) and Banff 2005 classifications (TIF) for borderline change may have different implications.

Treatment of severe symptomatic hyponatremia.

Hyponatremia is the most common electrolyte abnormality seen in the hospital. Severe symptomatic hyponatremia is associated with grave consequences including cerebral edema, brain herniation, seizures, obtundation, coma, and respiratory arrest. However, rapid correction of chronic severe hyponatremia may lead to osmotic demyelination syndrome (ODS) and even death. Given the serious consequences of severe hyponatremia or its inadvertent overcorrection, it is of paramount importance for the clinician to be aware of the various scenarios in which hyponatremic patients can present and tailor the management strategies accordingly. We present here a case of severe hyponatremia of unknown duration with the presenting plasma sodium level of 95 mmol/L and use it to illustrate the various treatment strategies - proactive, reactive, or rescue therapy - along with the physiological basis to support these approaches.

Intravascular Iodinated Contrast Is an Independent Cause of Acute Kidney Injury Following Coronary Angiography.

OBJECTIVES: Recent studies have questioned whether intravascular iodinated contrast remains an independent cause of acute kidney injury (AKI). We sought to assess whether iodinated contrast administered during coronary angiography is an independent cause of AKI. METHODS: We identified all of the patients who underwent coronary angiography between July 1, 2015 and June 30, 2017 with a discharge diagnosis of AKI that developed within 7 days following angiography. Using chart review, we categorized patients as having multifactorial AKI if ≥1 insults other than intravascular contrast potentially contributed to kidney injury or contrast-induced AKI (CI-AKI) if the only insult was contrast administration. We compared the severity of AKI and renal function upon discharge between patients with CI-AKI and multifactorial AKI. RESULTS: We identified 78 patients who experienced AKI within 7 days following angiography, 10 (13%) of whom had CI-AKI and 68 of whom (87%) experienced multifactorial AKI. Nine (90%) patients with CI-AKI manifested stage 1 disease, 1 (10%) had stage 2 disease, and 9 (90%) experienced full recovery of kidney function. More patients with multifactorial AKI developed stage 2 or 3 disease (42% vs 10%, χ2 = 3.73, P = 0.05) and experienced either partial recovery of kidney function or persistent kidney impairment compared with patients with CI-AKI (25% vs 10%, χ2 = 1.9, P = 0.17), although the latter comparison was not statistically significant. CONCLUSIONS: The intravascular administration of iodinated contrast remains an independent cause of AKI. Compared with those with multifactorial AKI, patients with CI-AKI appear to be more likely to experience mild decrements in kidney function that recover completely.

Does Kidney Transplantation Affect Sleep and Fatigue in Patients With Kidney Disease?

BACKGROUND: Sleep disorders and fatigue are highly prevalent in chronic kidney disease (CKD) and end-stage kidney disease (ESKD) patients but there is limited evidence on the effect of kidney transplant (KTx) on these. METHODS: In a prospective cohort study of patients with advanced CKD (estimated glomerular filtration rate<30 mL/min/1.73 m2) or ESKD, polysomnography and patient-reported symptom assessments were conducted. Pre- and post-KTx changes in sleep apnea (SA) severity (measured by apnea hypopnea index [AHI]) were analyzed and compared with patients who did not receive KTx. Regression models were used to examine predictors of SA severity. RESULTS: Among 77 patients (mean age 51 y, BMI 29 kg/m2, 66% males, 23% ESKD), 61% had SA at baseline. Among 39 KTx recipients, 56% had SA, with 39% having moderate-severe SA after 10 ± 5.6 months post-KTx. There was no difference in AHI in either the KTx (median 6 versus 8; P = 0.37) or no-KTx (median 15 versus 16; P = 0.61) groups after an average of 19.9 ± 8.9 months. KTx led to significant clinically meaningful improvements in fatigue and health-related quality of life (adjusted effect size 0.3-0.6). In multivariable regression, baseline AHI was the only significant predictor of SA severity (adjusted ß = 3.6/5 units, 95% confidence interval 2.1, 5.2) after adjusting for KTx status, age, sex, and body mass index. CONCLUSIONS: More than half of the KTx recipients had SA. There was no significant change in SA severity with KTx. Clinically meaningful moderate size improvements in patient-reported fatigue and health-related quality of life may be seen with KTx.

Continuous Renal Replacement Therapy: Who, When, Why, and How.

Continuous renal replacement therapy (CRRT) is commonly used to provide renal support for critically ill patients with acute kidney injury, particularly patients who are hemodynamically unstable. A variety of techniques that differ in their mode of solute clearance may be used, including continuous venovenous hemofiltration with predominantly convective solute clearance, continuous venovenous hemodialysis with predominantly diffusive solute clearance, and continuous venovenous hemodiafiltration, which combines both dialysis and hemofiltration. The present article compares CRRT with other modalities of renal support and reviews indications for initiation of renal replacement therapy, as well as dosing and technical aspects in the management of CRRT.

Urea for the Treatment of Hyponatremia.

BACKGROUND AND OBJECTIVES: Current therapies for hyponatremia have variable effectiveness and tolerability, and in certain instances, they are very expensive. We examined the effectiveness, safety, and tolerability of urea for the treatment of inpatient hyponatremia. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: We identified all patients hospitalized at the University of Pittsburgh Medical Center between July 2016 and August 2017 with hyponatremia (plasma sodium <135 mEq/L) who received urea, including a subgroup of patients who received urea as the sole drug therapy for hyponatremia (urea-only treated). We matched urea only-treated patients to a group of patients with hyponatremia who did not receive urea (urea untreated) and compared changes in plasma sodium at 24 hours and the end of therapy as well as the proportion of patients who achieved plasma sodium ≥135 mEq/L. We abstracted data on adverse events and reported side effects of urea. RESULTS: Fifty-eight patients received urea (7.5-90 g/d) over a median of 4.5 (interquartile range, 3-8) days and showed an increase in plasma sodium from 124 mEq/L (interquartile range, 122-126) to 131 mEq/L (interquartile range, 127-134; P<0.001). Among 12 urea only-treated patients, plasma sodium increased from 125 mEq/L (interquartile range, 122-127) to 131 mEq/L (interquartile range, 129-136; P=0.001) by the end of urea therapy. There was a larger increase in plasma sodium at 24 hours in urea only-treated patients compared with urea-untreated patients (2.5 mEq/L; interquartile range, 0-4.5 versus -0.5 mEq/L; interquartile range, -2.5 to 1.5; P=0.04), with no difference in change in plasma sodium by the end of therapy (6 mEq/L; interquartile range, 3.5-10 versus 5.5 mEq/L; interquartile range, 3-7.5; P=0.51). A greater proportion of urea only-treated patients achieved normonatremia, but this difference was not statistically significant (33% versus 8%; P=0.08). No patients experienced overly rapid correction of plasma sodium, and no serious adverse events were reported. CONCLUSIONS: Urea seems effective and safe for the treatment of inpatient hyponatremia, and it is well tolerated.

Xenotransplantation.

The transplantation of living cells, tissues or organs from one species to another is termed xenotransplantation. The history of xenotransplantation is as old as allogeneic transplantation itself. Early attempts were made at a time when the immunologic basis of organ rejection were poorly understood. The advent of potent immunosuppressive medications along with the parallel advances in the field of genetic engineering has provided a fresh perspective on the role of xenotransplantation as a means to alleviate the disparity between the number of candidates on the waitlist and the available organs. As the science behind xenotransplantation advances, the transplantation community must take it upon themselves to educate the community at large regarding both the benefits and potential risks of this promising field.

Dyskalemia in Chronic Kidney Disease: How Concerned Should We Be?

CONTEXT: The widespread use of diuretics, potassium supplements, and medications that block renin angiotensin system puts the chronic kidney disease (CKD) population at high risk for dyskalemia, both hyperkalemia and hypokalemia. The optimal potassium level in a CKD patient is unknown. Subject of review: Two recent studies found conflicting results on the association of dyskalemia with outcomes. The Renal Research Institute CKD study [Clin J Am Soc Nephrol 2010; 5: 762-769] found increased mortality and incidence of end-stage renal disease (ESRD) with mild to moderate hypokalemia, whereas hyperkalemia was not significantly associated, compared to eukalemia. On the other hand, the Multi-Ethnic Study of Atherosclerosis (MESA)/Cardiovascular Health Study [Clin J Am Soc Nephrol 2017; 12: 245-252] showed both cardiovascular and noncardiovascular mortality to be higher with hyperkalemic patients, whereas associations with hypokalemic patients were statistically nonsignificant. Second opinion: If mild hypo- or hyperkalemia is associated with adverse outcomes, is it related to the hyperkalemia per se or to conditions associated with dyskalemia, such as kidney disease or cardiovascular disease? We interpret these articles in the context of criteria to support causality in epidemiologic studies. The cardiovascular effects of dyskalemia is well described and there is biological plausibility for increased cardiovascular mortality but the association of increased non-cardiovascular mortality with dyskalemia has little mechanistic basis. The explanation for a causal association of dyskalemia with ESRD is not adequate. Based on current evidence, targeting a potassium level of 4-5 mmol/L can be considered safe.

Duodenal obstruction as the presenting manifestation of recurrent breast cancer.

In this report, we present a case of duodenal obstruction as the initial presenting manifestation of a patient with recurrent invasive lobular breast carcinoma.